Leonurine_hydrochloride_DataSheet_MedChemExpress
盐酸纳美芬FDA的说明书
Revex (nalmefene hydrochloride injection)Rx onlyDESCRIPTIONREVEX (nalmefene hydrochloride injection), an opioid antagonist, is a 6-methylene analogue of naltrexone. The chemical structure is shown below:Molecular Formula: C21H25NO3•HClMolecular Weight: 375.9, CAS # 58895-64-0Chemical Name: 17-(Cyclopropylmethyl)-4,5〈-epoxy-6-methylenemorphinan-3,14-diol, hydrochloride salt.Nalmefene hydrochloride is a white to off-white crystalline powder which is freely soluble in water up to 130 mg/mL and slightly soluble in chloroform up to 0.13 mg/mL, with a pK a of 7.6.REVEX is available as a sterile solution for intravenous, intramuscular, and subcutaneous administration in two concentrations, containing 100 µg or 1.0 mg of nalmefene free base per mL. The 100 µg/mL concentration contains 110.8 µg of nalmefene hydrochloride and the 1.0 mg/mL concentration contains 1.108 mg of nalmefene hydrochloride per mL. Both concentrations contain 9.0 mg of sodium chloride per mL and the pH is adjusted to 3.9 with hydrochloric acid.Concentrations and dosages of REVEX are expressed as the free base equivalent of nalmefene.CLINICAL PHARMACOLOGYPharmacodynamicsREVEX prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Pharmacodynamic studies have shown that REVEX has a longer duration of action than naloxone at fully reversing doses. REVEX has no opioid agonist activity.REVEX is not known to produce respiratory depression, psychotomimetic effects, or pupillary constriction. No pharmacological activity was observed when REVEX was administered in the absence of opioid agonists.REVEX has not been shown to produce tolerance, physical dependence, or abuse potential.REVEX can produce acute withdrawal symptoms in individuals who are opioid dependent.PharmacokineticsNalmefene exhibited dose proportional pharmacokinetics following intravenousadministration of 0.5 mg to 2.0 mg. Pharmacokinetic parameters for nalmefene after a 1mg intravenous administration in adult male volunteers are listed in Table 1.Table 1: Mean (CV%) Nalmefene Pharmacokinetic ParametersIn Adult Males Following a 1 mg Intravenous DoseParameter Young, N=18 Elderly, N=1162-80 Age 19-32Cp at 5 min. (ng/mL) 3.7 (29) 5.8 (38)Vdss (L/kg) 8.6 (19) 8.6 (29)Vc (L/kg) 3.9 (29) 2.8 (41)AUC0-inf (ng-hr/mL) 16.6 (27) 17.3 (14)Terminal T1/2 (hr) 10.8 (48) 9.4 (49)Clplasma (L/hr/kg) 0.8 (23) 0.8 (18)ABSORPTIONNalmefene was completely bioavailable following intramuscular or subcutaneousadministration in 12 male volunteers relative to intravenous nalmefene. The relativebioavailabilities of intramuscular and subcutaneous routes of administration were 101.5%± 8.1% (Mean ± SD) and 99.7% ± 6.9%, respectively. Nalmefene will be administeredprimarily as an intravenous bolus, however, nalmefene can be given intra-muscularly(IM) or subcutaneously (SC) if venous access cannot be established. While the time tomaximum plasma nalmefene concentration was 2.3 ± 1.1 hours following intramuscularand 1.5 ± 1.2 hours following subcutaneous administrations, therapeutic plasmaconcentrations are likely to be reached within 5-15 minutes after a 1 mg dose in anemergency. Because of the variability in the speed of absorption for IM & SC dosing, andthe inability to titrate to effect, great care should be taken if repeated doses must be givenby these routes.DISTRIBUTIONFollowing a 1 mg parenteral dose, nalmefene was rapidly distributed. In a study of brainreceptor occupancy, a 1 mg dose of nalmefene blocked over 80% of brain opioidreceptors within 5 minutes after administration. The apparent volumes of distributioncentrally (Vc) and at steady-state (Vdss) are 3.9 ± 1.1 L/kg and 8.6 ± 1.7 L/kg,respectively. Ultrafiltration studies of nalmefene have demonstrated that 45% (CV 4.1%)is bound to plasma proteins over a concentration range of 0.1 to 2 µg/mL. An in vitrodetermination of the distribution of nalmefene in human blood demonstrated thatnalmefene distributed 67% (CV 8.7%) into red blood cells and 39% (CV 6.4%) intoplasma. The whole blood to plasma ratio was 1.3 (CV 6.6%) over the nominalconcentration range in whole blood from 0.376 to 30 ng/mL.METABOLISMNalmefene is metabolized by the liver, primarily by glucuronide conjugation, andexcreted in the urine. Nalmefene is also metabolized to trace amounts of an N-dealkylated metabolite. Nalmefene glucuronide is inactive and the N-dealkylatedmetabolite has minimal pharmacological activity. Less than 5% of nalmefene is excretedin the urine unchanged. Seventeen percent (17%) of the nalmefene dose is excreted in thefeces. The plasma concentration-time profile in some subjects suggests that nalmefene undergoes enterohepatic recycling..ELIMINATIONAfter intravenous administration of 1 mg REVEX to normal males (ages 19-32), plasma concentrations declined biexponentially with a redistribution and a terminal elimination half-life of 41 ± 34 minutes and 10.8 ± 5.2 hours, respectively. The systemic clearance of nalmefene is 0.8 ± 0.2 L/hr/kg and the renal clearance is 0.08 ± 0.04 L/hr/kg.Special PopulationsELDERLYDose proportionality was observed in nalmefene AUC0-inf following 0.5 to 2 mg intravenous administration to elderly male subjects. Following a 1 mg intravenous nalmefene dose, there were no significant differences between young (19-32 years) and elderly (62-80 years) adult male subjects with respect to plasma clearance, steady-state volume of distribution, or half-life. There was an apparent age-related decrease in the central volume of distribution (young: 3.9 ± 1.1 L/kg, elderly: 2.8 ± 1.1 L/kg) that resulted in a greater initial nalmefene concentration in the elderly group. While initial nalmefene plasma concentrations were transiently higher in the elderly, it would not be anticipated that this population would require dosing adjustment. No clinical adverse events were noted in the elderly following the 1 mg intravenous nalmefene dose. PATIENTS WITH HEPATIC IMPAIRMENTSubjects with hepatic disease, when compared to matched normal controls, had a 28.3% decrease in plasma clearance of nalmefene (0.56 ± 0.21 L/hr/kg versus 0.78 ± 0.24L/hr/kg, respectively). Elimination halflife increased from 10.2 ± 2.2 hours to 11.9 ± 2.0 hours in the hepatically impaired. No dosage adjustment is recommended since nalmefene will be administered as an acute course of therapy.PATIENTS WITH RENAL IMPAIRMENTThere was a statistically significant 27% decrease in plasma clearance of nalmefene in the end-stage renal disease (ESRD) population during interdialysis (0.57 ± 0.20 L/hr/kg) and a 25% decreased plasma clearance in the ESRD population during intradialysis (0.59 ± 0.18 L/hr/kg) compared to normals (0.79 ± 0.24 L/hr/kg). The elimination half-life was prolonged in ESRD patients from 10.2 ± 2.2 hours in normals to 26.1 ± 9.9 hours. (See DOSAGE AND ADMINISTRATION.)GENDER DIFFERENCESThere has not been sufficient pharmacokinetic study to make a definitive statement as to whether the pharmacokinetics of nalmefene differs between the genders.CLINICAL TRIALSREVEX has been administered to reverse the effects of opioids after general anesthesia and in the treatment of overdose. It has also been used to reverse the systemic effects of intrathecal opioids.Reversal of Postoperative Opioid DepressionREVEX (nalmefene hydrochloride injection) (N=326) was studied in 5 controlled trials in patients who had received morphine or fentanyl intraoperatively. The primary efficacy criterion was the reversal of respiratory depression. A positive reversal was defined asboth an increase in respiratory rate by 5 breaths per minute and a minimum respiratory rate of 12 breaths per minute. Five minutes after administration, initial single REVEX doses of 0.1, 0.25, 0.5, or 1.0 µg/kg had effectively reversed respiratory depression in a dose-dependent manner. Twenty minutes after initial administration, respiratory depression had been effectively reversed in most patients receiving cumulative doses within the recommended range (0.1 to 1.0 µg/kg). Total doses of REVEX above 1.0µg/kg did not increase the therapeutic response. The postoperative administration of REVEX at the recommended doses did not prevent the analgesic response to subsequently administered opioids.Reversal of the Effect of Intrathecally Administered OpioidsIntravenous REVEX at doses of 0.5 and 1.0 µg/kg was administered to 47 patients given intrathecal morphine. One to 2 doses of 0.5 and 1.0 µg/kg REVEX reversed respiratory depression in most patients. The administration of REVEX at the recommended doses did not prevent the analgesic response to subsequently administered opioids. Management of Known or Suspected Opioid OverdoseREVEX (N=284) at doses of 0.5 mg to 2.0 mg was studied in 4 trials of patients who were presumed to have taken an opioid overdose. REVEX doses of 0.5 mg to 1.0 mg effectively reversed respiratory depression within 2 to 5 minutes in most patients subsequently confirmed to have opioid overdose. A total dose greater than 1.5 mg did not increase the therapeutic response.INDICATIONS AND USAGEREVEX is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids.REVEX is indicated in the management of known or suspected opioid overdose. CONTRAINDICATIONSREVEX is contraindicated in patients with a known hypersensitivity to the product. WARNINGSUse of REVEX in EmergenciesREVEX, like all drugs in this class, is not the primary treatment for ventilatory failure. In most emergency settings, treatment with REVEX should follow, not precede, the establishment of a patent airway, ventilatory assistance, administration of oxygen, and establishment of circulatory access.Risk of Recurrent Respiratory DepressionAccidental overdose with long acting opioids [such as methadone and levo-alpha-acetylmethadol (LAAM)] may result in prolonged respiratory depression. Respiratory depression in both the postoperative and overdose setting may be complex and involve the effects of anesthetic agents, neuromuscular blockers, and other drugs. While REVEX has a longer duration of action than naloxone in fully reversing doses, the physician should be aware that a recurrence of respiratory depression is possible, even after an apparently adequate initial response to REVEX treatment.Patients treated with REVEX should be observed until, in the opinion of the physician, there is no reasonable risk of recurrent respiratory depression. PRECAUTIONSGeneralCARDIOVASCULAR RISKS WITH NARCOTIC ANTAGONISTSPulmonary edema, cardiovascular instability, hypotension, hypertension, ventricular tachycardia, and ventricular fibrillation have been reported in connection with opioid reversal in both postoperative and emergency department settings. In many cases, these effects appear to be the result of abrupt reversal of opioid effects.Although REVEX has been used safely in patients with pre-existing cardiac disease, all drugs of this class should be used with caution in patients at high cardiovascular risk or who have received potentially cardiotoxic drugs. (See DOSAGE AND ADMINISTRATION.)RISK OF PRECIPITATED WITHDRAWALREVEX, like other opioid antagonists, is known to produce acute withdrawal symptoms and, therefore, should be used with extreme caution in patients with known physical dependence on opioids or following surgery involving high doses of opioids. Imprudent use or excessive doses of opioid antagonists in the postoperative setting has been associated with hypertension, tachycardia, and excessive mortality in patients at high risk for cardiovascular complications. (See PRECAUTIONS.)INCOMPLETE REVERSAL OF BUPRENORPHINEPreclinical studies have shown that nalmefene at doses up to 10 mg/kg (437 times the maximum recommended human dose) produced incomplete reversal of buprenorphine-induced analgesia in animal models. This appears to be a consequence of a high affinity and slow displacement of buprenorphine from the opioid receptors. Hence, REVEX may not completely reverse buprenorphine-induced respiratory depression.Drug InteractionsREVEX has been administered after benzodiazepines, inhalational anesthetics, muscle relaxants, and muscle relaxant antagonists administered in conjunction with general anesthesia. It also has been administered in outpatient settings, both in trials in conscious sedation and in the emergency management of overdose following a wide variety of agents. No deleterious interactions have been observed.Preclinical studies have shown that both flumazenil and nalmefene can induce seizures in animals. The coadministration of both flumazenil and nalmefene produced fewer seizures than expected in a study in rodents, based on the expected effects of each drug alone. Based on these data, an adverse interaction from the coadministration of the two drugs is not expected, but physicians should remain aware of the potential risk of seizures from agents in these classes.Carcinogenesis, Mutagenesis, Impairment of FertilityNalmefene did not have mutagenic activity in the Ames test with five bacterial strains or the mouse lymphoma assay. Clastogenic activity was not observed in the mouse micronucleus test or in the cytogenic bone marrow assay in rats. However, nalmefene did exhibit a weak but significant clastogenic activity in the human lymphocyte metaphase assay in the absence but not in the presence of exogenous metabolic activation. Oral administration of nalmefene up to 1200 mg/m2/day did not affect fertility, reproductive performance, and offspring survival in rats.Use in PregnancyPREGNANCY CATEGORY BReproduction studies have been performed in rats (up to 1200 mg/m2/day) and rabbits (up to 2400 mg/m2/day) by oral administration of nalmefene and in rabbits by intravenous administration up to 96 mg/m2/day (114 times the human dose). There was no evidence of impaired fertility or harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.Nursing MothersNalmefene and its metabolites were secreted into rat milk, reaching concentrations approximately three times those in plasma at one hour and decreasing to about half the corresponding plasma concentrations by 24 hours following bolus administration. As no clinical information is available, caution should be exercised when REVEX is administered to a nursing woman.Use in Pediatric PatientsSafety and effectiveness of REVEX in pediatric patients have not been established.Use in NeonatesThe safety and effectiveness of REVEX in neonates have not been established in clinical studies. In a preclinical study, nalmefene was administered by subcutaneous injection to rat pups at doses up to 205 mg/m2/day throughout maternal lactation without producing adverse effects. A preclinical study evaluating the irritancy of the dosage form following arterial and venous administration in animals showed no vascular irritancy.REVEX (nalmefene hydrochloride injection) should only be used in the resuscitation of the newborn when, in the opinion of the treating physician, the expected benefits outweigh the risks.Geriatric UseClinical studies of Revex did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.ADVERSE REACTIONSAdverse event information was obtained following administration of REVEX to 152 normal volunteers and in controlled clinical trials to 1127 patients for the treatment of opioid overdose or for postoperative opioid reversal.Nalmefene was well tolerated and showed no serious toxicity during experimental administration to healthy individuals, even when given at 15 times the highest recommended dose. In a small number of subjects, at doses exceeding the recommendedREVEX dose, nalmefene produced symptoms suggestive of reversal of endogenousopioids, such as have been reported for other narcotic antagonist drugs. These symptoms(nausea, chills, myalgia, dysphoria, abdominal cramps, and joint pain) were usuallytransient and occurred at very low frequency.Such symptoms of precipitated opioid withdrawal at the recommended clinical doseswere seen in both postoperative and overdose patients who were later found to have hadhistories of covert opioid use. Symptoms of precipitated withdrawal were similar to thoseseen with other opioid antagonists, were transient following the lower doses used in thepostoperative setting, and more prolonged following the administration of the largerdoses used in the treatment of overdose.Tachycardia and nausea following the use of nalmefene in the postoperative setting werereported at the same frequencies as for naloxone at equivalent doses. The risk of boththese adverse events was low at doses giving partial opioid reversal and increased withincreases in dose. Thus, total doses larger than 1.0 µg/kg in the postoperative setting and1.5 mg/70 kg in the treatment of overdose are not recommended.Relative Frequencies of Common Adverse ReactionsWith an Incidence Greater than 1%(all patients, all clinical settings)Adverse EventNalmefene Naloxone PlaceboN=1127N=369N=776% Nausea 18%18%Vomiting 9% 7% 4%- Tachycardia 5%8%- Hypertension 5%7%Postoperative pain 4% 4% N/A- Fever 3%4%Dizziness 3% 4% 1%Headache 1% 1% 4%Chills 1%-1%- Hypotension 1%1%- Vasodilatation 1%1%Incidence less than 1%CARDIOVASCULAR: Bradycardia, arrhythmiaDIGESTIVE: Diarrhea, dry mouthNERVOUS SYSTEM: Somnolence, depression, agitation, nervousness, tremor,confusion, withdrawal syndrome, myoclonusRESPIRATORY: PharyngitisSKIN: PruritusUROGENITAL: Urinary retentionThe incidence of adverse events was highest in patients who received more than therecommended dose of REVEX.Laboratory findings: Transient increases in CPK were reported as adverse events in 0.5%of the postoperative patients studied. These increases were believed to be related tosurgery and not believed to be related to the administration of REVEX. Increases in AST were reported as adverse events in 0.3% of the patients receiving either nalmefene or naloxone. The clinical significance of this finding is unknown. No cases of hepatitis or hepatic injury due to either nalmefene or naloxone were observed in the clinical trials. DRUG ABUSE AND DEPENDENCEREVEX is an opioid antagonist with no agonist activity. It has no demonstrated abuse potential, is not addictive, and is not a controlled substance.OVERDOSAGEIntravenous doses of up to 24 mg of nalmefene, administered to healthy volunteers in the absence of opioid agonists, produced no serious adverse reactions, severe signs or symptoms, or clinically significant laboratory abnormalities. As with all opioid antagonists, use in patients physically dependent on opioids can result in precipitated withdrawal reactions that may result in symptoms that require medical attention. Treatment of such cases should be symptomatic and supportive. Administration of large amounts of opioids to patients receiving opioid antagonists in an attempt to overcome a full blockade has resulted in adverse respiratory and circulatory reactions.DOSAGE AND ADMINISTRATIONImportant Information - Dosage FormsREVEX is supplied in two concentrations that can be identified by their color coded container labels: a concentration suitable for postoperative use (100 µg/mL) in a blue labeled ampul containing ONE (1) mL and a concentration suitable for the management of overdose (1 mg/mL, 10 times as concentrated, 20 times as much drug) in a green labeled ampul containing TWO (2) mL. Proper steps should be taken to prevent use of the incorrect concentration.General PrinciplesREVEX should be titrated to reverse the undesired effects of opioids. Once adequate reversal has been established, additional administration is not required and may actually be harmful due to unwanted reversal of analgesia or precipitated withdrawal.Duration of ActionThe duration of action of REVEX is as long as most opioid analgesics. The apparent duration of action of REVEX will vary, however, depending on the half-life and plasma concentration of the narcotic being reversed, the presence or absence of other drugs affecting the brain or muscles of respiration, and the dose of REVEX administered. Partially reversing doses of REVEX (1 µg/kg) lose their effect as the drug is redistributed through the body, and the effects of these low doses may not last more than 30-60 minutes in the presence of persistent opioid effects. Fully reversing doses (1 mg/70 kg) have been shown to last many hours in both experimental and clinical studies, but may complicate the management of patients who are in pain, at high cardiovascular risk, or who are physically dependent on opioids.The recommended doses represent a compromise between a desirable controlled reversal and the need for prompt response and adequate duration of action. Using higher dosages or shorter intervals between incremental doses is likely to increase the incidence and severity of symptoms related to acute withdrawal such as nausea, vomiting, elevated blood pressure, and anxiety.Patients Tolerant to or Physically Dependent on OpioidsREVEX may cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids. These patients should be closely observed for symptoms of withdrawal following administration of the initial and subsequent injections of REVEX. Subsequent doses should be administered with intervals of at least 2-5 minutes between doses to allow the full effect of each incremental dose of REVEX to be reached.Recommended Doses for Reversal of Postoperative Opioid Depression Use 100 µg/mL dosage strength (blue label) and see Table 2 for initial doses.The goal of treatment with REVEX in the postoperative setting is to achieve reversal of excessive opioid effects without inducing a complete reversal and acute pain. This is best accomplished with an initial dose of 0.25 µg/kg followed by 0.25 µg/kg incremental doses at 2-5 minute intervals, stopping as soon as the desired degree of opioid reversal is obtained. A cumulative total dose above 1.0 µg/kg does not provide additional therapeutic effect.Table 2: Reversal of Postoperative Opioid DepressionmL of REVEXBody Weight100 µg/mL Solution50 kg 0.12560 kg 0.15070 kg 0.17580 kg 0.20090 kg 0.225100 kg 0.250In cases where the patient is known to be at increased cardiovascular risk, it may be desirable to dilute REVEX 1:1 with saline or sterile water and use smaller initial and incremental doses of 0.1 µg/kg.Management of Known or Suspected Opioid OverdoseUse 1.0 mg/mL dosage strength (green label).The recommended initial dose of REVEX for non-opioid dependent patients is 0.5 mg/70 kg. If needed, this may be followed by a second dose of 1.0 mg/70 kg, 2-5 minutes later. If a total dose of 1.5 mg /70 kg has been administered without clinical response, additional REVEX (nalmefene hydrochloride injection) is unlikely to have an effect. Patients should not be given more REVEX than is required to restore the respiratory rate to normal, thus minimizing the likelihood of cardiovascular stress and precipitated withdrawal syndrome.If there is a reasonable suspicion of opioid dependency, a challenge dose of REVEX 0.1 mg/70 kg should be administered initially. If there is no evidence of withdrawal in 2 minutes, the recommended dosing should be followed.REVEX had no effect in cases where opioids were not responsible for sedation and hypoventilation. Therefore, patients should only be treated with REVEX when thelikelihood of an opioid overdose is high, based on a history of opioid overdose or the clinical presentation of respiratory depression with concurrent pupillary constriction. Repeated DosingREVEX is the longest acting of the currently available parenteral opioid antagonists. If recurrence of respiratory depression does occur, the dose should again be titrated to clinical effect using incremental doses to avoid over-reversal.Hepatic and Renal DiseaseHepatic disease and renal failure substantially reduce the clearance of nalmefene (see Pharmacokinetics). For single episodes of opioid antagonism, adjustment of REVEX dosage is not required. However, in patients with renal failure, the incremental doses should be delivered slowly (over 60 seconds) to minimize the hypertension and dizziness reported following the abrupt administration of nalmefene to such patients.Loss of Intravenous AccessShould intravenous access be lost or not readily obtainable, a pharmacokinetic study has shown that a single dose of REVEX should be effective within 5-15 minutes after intramuscular or subcutaneous doses of 1.0 mg. (See Pharmacokinetics.)SAFETY AND HANDLINGREVEX is distributed in sealed ampuls which represent no known risk to health care workers. As with all parenterals, care should be taken to prevent the generation and inhalation of aerosols during preparation and use. Dermal absorption of spilled REVEX should be prevented by prompt removal of contaminated clothing and rinsing the skin thoroughly with cool water.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.HOW SUPPLIEDREVEX (nalmefene hydrochloride injection) is available in the following presentations: An ampul containing 1 mL of 100 µg/mL nalmefene base (Blue Label) Box of 10 (NDC 10019-315-21)An ampul containing 2 mL of 1 mg/mL nalmefene base (Green Label) Box of 10 (NDC 10019-311-22)Store at controlled room temperature.REVEX is a registered trademark of Ivax Laboratories, Inc.Baxter is a trademark of Baxter International, Inc.Manufactured forBaxter Healthcare CorporationDeerfield, IL 60015 USAby: Taylor PharmaceuticalsDecatur, IL 62525For Product Inquiry 1 800 ANA DRUG (1-800-262-3784)U.S. Patent No. 4,535,157MLT-01167/1.011。
雷诺嗪 药典标准
雷诺嗪药典标准
雷诺嗪（Ranolazine）是一种心血管选择性抗缺血药，其药典标准主要参考美国药典（USP）或者中国药典（Ch.P）中关于雷诺嗪的规定。
以下是雷诺嗪的药典标准概述。
1.品名：雷诺嗪
2.化学名称：5-[2-[[4-[(2-氰基乙基)氨基]苯基]-1,3-二氧杂-2-丙醇]-2-甲基-1,3-二氧杂-2-丙醇
3.分子式：C24H31N3O4
4.分子量：433.51
5.CAS号：95635-55-5
6.外观：白色或类白色结晶性粉末
7.熔点：178-182℃
8.用途：抗心绞痛药
9.制剂：片剂、缓释片剂
10.规格：500mg、1000mg（美国）；375mg、500mg、750mg（英国）
需要注意的是，雷诺嗪的药典标准可能会随着不同国家和地区的药典版本而有所差异。
在实际应用中，应遵循医生开具的处方以及药品说明书上的用法用量。
如有疑问，请咨询专业医生。
大肠杆菌高产L丙氨酸
APPLIED GENETICS AND MOLECULAR BIOTECHNOLOGYProduction of L-alanine by metabolically engineered Escherichia coliXueli Zhang&Kaemwich Jantama&J.C.Moore&K.T.Shanmugam&L.O.IngramReceived:23May2007/Revised:13August2007/Accepted:16August2007/Published online:15September2007 #Springer-Verlag2007Abstract Escherichia coli W was genetically engineered to produce L-alanine as the primary fermentation product from sugars by replacing the native D-lactate dehydroge-nase of E.coli SZ194with alanine dehydrogenase from Geobacillus stearothermophilus.As a result,the heterolo-gous alanine dehydrogenase gene was integrated under the regulation of the native D-lactate dehydrogenase(ldhA) promoter.This homologous promoter is growth-regulated and provides high levels of expression during anaerobic fermentation.Strain XZ111accumulated alanine as the primary product during glucose fermentation.The methyl-glyoxal synthase gene(mgsA)was deleted to eliminate low levels of lactate and improve growth,and the catabolic alanine racemase gene(dadX)was deleted to minimize conversion of L-alanine to D-alanine.In these strains,re-duced nicotinamide adenine dinucleotide oxidation during alanine biosynthesis is obligately linked to adenosine triphosphate production and cell growth.This linkage provided a basis for metabolic evolution where selection for improvements in growth coselected for increased glycolytic flux and alanine production.The resulting strain, XZ132,produced1,279mmol alanine from120g l−1 glucose within48h during batch fermentation in the mineral salts medium.The alanine yield was95%on a weight basis(g g−1glucose)with a chiral purity greater than99.5%L-alanine.Keywords Alanine.Fermentation.E.coli.Evolution. GlycolysisIntroductionWorldwide production of L-alanine has been estimated at 500tons per year(Ikeda2003).In pharmaceutical and veterinary applications,L-alanine is used with other L-amino acids as a pre-and postoperative nutrition therapy(Hols et al.1999).Alanine is also used as a food additive because of its sweet taste(Lee et al.2004).The use of L-alanine is limited in part by the current high cost.L-Alanine is pro-duced commercially by the enzymatic decarboxylation of L-aspartic acid using immobilized cells or cell suspensions of Pseudomonas dacunhae as a biocatalyst with a yield greater than90%(Shibatani et al.1979).The substrate for this enzymatic production process,L-aspartate,is usually pro-duced from fumarate by enzymatic catalysis with aspartate ammonia-lyase.Fumaric acid is produced primarily from petroleum,a nonrenewable feedstock.An efficient fermen-tative process with a renewable feedstock such as glucose offers the potential to reduce L-alanine cost and facilitate a broad expansion of the alanine market into other products.Alanine is a central intermediate(Fig.1)and an essential component of cellular proteins.Most microorganisms produce alanine only for biosynthesis using a glutamate–pyruvate transaminase(Hashimoto and Katsumata1998). Some organisms such as Arthrobacter oxydans(Hashimoto and Katsumata1993;Hashimoto and Katsumata1998; Hashimoto and Katsumata1999),Bacillus sphaericus (Ohashima and Soda1979),and Clostridium sp.P2Appl Microbiol Biotechnol(2007)77:355–366DOI10.1007/s00253-007-1170-yElectronic supplementary material The online version of this article (doi:10.1007/s00253-007-1170-y)contains supplementary material, which is available to authorized users.X.Zhang:J.C.Moore:K.T.Shanmugam:L.O.Ingram(*) Department of Microbiology and Cell Science,University of Florida,Box110700,Gainesville,FL32611,USAe-mail:ingram@K.JantamaDepartment of Chemical Engineering,University of Florida, Gainesville,FL32611,USA(Orlygsson et al.1995)produce alanine from pyruvate and ammonia using an reduced nicotinamide adenine dinucleo-tide (NADH)-linked alanine dehydrogenase (ALD).How-ever,fermentations are slow,and yields from the best natural producers are typically 60%or less because of coproduct formation (Hashimoto and Katsumata 1998;Table 1).Plasmid-borne genes encoding NADH-linked ALD have been tested as an approach to develop improved biocatalysts with varying degrees of success (Table 1).Engineered strains of Zymomonas mobilis CP4expressing the B.sphaericus alaD gene produced low levels of racemic alanine during the anaerobic fermentation of 5%glucose (Uhlenbusch et al.1991).A native chromosomal lactate dehydrogenase gene (ldhA )-deleted strain of Lactococcus lactis containing a mutation in alanine racemase was engineered in a similar fashion and produced 12.6g l −1L -alanine from 1.8%glucose (Hols et al.1999).An Escherichia coli aceF ldhA double mutant containing pTrc99A-alaD plasmid produced 32g l −1racemic alanine in 27h during a two-stage (aerobic and anaerobic)fermentation with a yield of 0.63g alanine g −1glucose (Lee et al.2004).With further gene deletions and process optimization,the racemic alanine titer wasincreasedFig.1Alanine pathway in recombinant E.coli .a Native and recom-binant fermentation pathways.The foreign gene,G.stearothermophilus alaD ,is shown in bold .G.stearothermophilus alaD coding region and transcriptional terminator were integrated into the native ldhA gene under transcriptional control of the ldhA promoter.Solid stars represent deletions of native genes in XZ132.Note that the native biosynthetic route for alanine production is omitted for simplicity.ackA Acetate kinase,adhE alcohol/aldehyde dehydrogenase,alaD alanine dehydro-genase (Geobacillus stearothermophilus XL-65-6),aldA aldehyde dehydrogenase A,aldB aldehyde dehydrogenase B,alr alanine race-mase 1,dadX alanine racemase 2,frd fumarate reductase,gloA glyoxalase I,gloB glyoxalase II,gloC glyoxalase III,ldhA D -lactate dehydrogenase,mdh malate dehydrogenase,mgsA methylglyoxal synthase,pflB pyruvate –formate lyase,ppc phosphoenolpyruvate carboxylase,pta phosphate acetyltransferase.b Coupling of ATP production and growth to NADH oxidation and L -alanine production.Glucose is metabolized to pyruvate,ATP,and NADH.Energy conserved in ATP is utilized for growth and homeostasis,regenerating ADP.NADH is oxidized by alanine formation allowing glycolysis and ATP production to continueT a b l e 1C o m p a r i s o n o f a l a n i n e -p r o d u c i n g s t r a i n sO r g a n i s m s M o d i f i e d p r o p e r t yM e d i a ,s u b s t r a t e a n d p r o c e s s c o n d i t i o n sT i m e (h )A l a n i n e (g l −1)Y i e l d (%)L -A l a n i n ep u r i t y (%)R e f e r e n c e E .c o l i X Z 132I n t e g r a t e d G .s t e a r o t h e r m o p h i l u s a l a D ;Δp f l ,Δa c k A ,Δa d h E ,Δl d h A ,Δm g s A ,Δd a d XM i n e r a l m e d i u m ,b a t c h ,g l u c o s e 120g l −148.0114.095>99T h i s s t u d yA r t h r o b a c t e r o x y d a n s H A P -1M i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1120825560.0H a s h i m o t o a n d K a t s u m a t a 1998A .o x y d a n s D A N 75A l a n i n e r a c e m a c e d e f i c i e n tM i n e r a l m e d i u m ,t w o -s t a g e f e d -b a t c h ,g l u c o s e 150g l −1,0.2g l −1D -a l a n i n e120775198H a s h i m o t o a n d K a t s u m a t a 1998E c o l i A L 1(p O B P 1)P l a s m i d w i t h A .o x y d a n s H A P -1a l a D M i n e r a l m e d i u m ,g l u c o s e 20g l −1,l i m i t e d o x y g e n40841N o t r e p o r t e dK a t s u m a t a a n d H a s h i m o t o 1996C o r y n e b a c t e r i u m g l u t a m i c u m A L 107(p O B P 107)P l a s m i d w i t h A .o x y d a n s H A P -1a l a DC o r n s t e e p l i q u o r ,g l u c o s e 200g l −1,4g l −1D L -a l a n i n e ,l i m i t e d o x y g e n 707136>99K a t s u m a t a a n d H a s h i m o t o 1996Z y m o m o n a s m o b i l i s C P 4(p Z Y 73)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D M i n e r a l s a l t s m e d i u m ,s i m p l e b a t c h ,g l u c o s e 50g l −126816N o t r e p o r t e dU h l e n b u s c h e t a l .1991L a c t o c o c c u s l a c t i s N Z 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h AR i c h m e d i u m (M 17),g l u c o s e 18g l −117137085–90H o l s e t a l .1999L .l a c t i s P H 3950(p N Z 2650)P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa l rR i c h m e d i u m (M 17),g l u c o s e 18g l −1,0.2g l −1D -a l a n i n e 17N o t k n o w nN o t k n o w n >99H o l s e t a l .1999E .c o l i A L S 887(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δl d h A ,Δa c e FY e a s t e x t r a c t ,t w o -s t a g e b a t c h ,g l u c o s e 50g l −1,a e r o b i c a i r 1l m i n −1273263N o t r e p o r t e d L e e e t a l .2004E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )223486N o t r e p o r t e d S m i t h e t a l .2006E .c o l i A L S 929(p T r c 99A -a l a D )P l a s m i d w i t h B .s p h a e r i c u s I F O 3525a l a D Δp f l ,Δp p s ,Δp o x B ,Δl d h A ,Δa c e E FY e a s t e x t r a c t a n d c a s a m i n o a c i d s ,t w o -s t a g e f e d -b a t c h (a e r o b i c c e l l g r o w t h a n d a n a e r o b i c f e r m e n t a t i o n )4888100N o t r e p o r t e d S m i t h e t a l .2006to88g l−1in a more complex process with yields ap-proaching the theoretical maximum(Smith et al.2006). However,this strain produced only racemic alanine,utilized multicopy plasmids requiring antibiotic selection,and required complex media with a complex multistage fermen-tation process(Smith et al.2006).In this study,we developed novel biocatalysts that pro-duce chirally pure L-alanine in batch fermentations without using plasmid-containing biocatalysts,antibiotics,or com-plex nutrients.The resulting strains are based on a deriva-tive of E.coli W(strain SZ194)that produces D-lactate (Zhou et al.2006b).The ldhA gene in SZ194was replaced with a single,chromosomally integrated copy of the ALD gene from the thermophile,Geobacillus stearothermophilus XL-65-6(formerly B.stearothermophilus;Lai and Ingram 1993).After additional deletions of alanine racemase (dadX)and methylglyoxal synthase(mgsA)and metabolic evolution,the resulting strain produced L-alanine at high titers(over1M)and yields in batch fermentations using the mineral salts medium.Materials and methodsStrains,plasmids,media,and growth conditionsThe strains and plasmids used in this study are listed in Table2.Strain SZ194was previously engineered from a derivative of E.coli W(ATCC9637)and served as a starting point for constructions(Zhou et al.2006b).G. stearothermophilus XL-65-6(Lai and Ingram1993)was used for cloning the ALD gene.During sequencing of chro-mosomal genes,we discovered a20-year-old error in culture labeling.Strain SZ194,the parent used to construct the alanine strains,is a derivative of E.coli W(ATCC9637). Other constructs for ethanol production and lactate produc-tion that have been reported previously as derivatives of E. coli B are now known to be derivates of E.coli W(ATCC 9637).Primers used in this study are listed in Table3.During strain construction,cultures were grown aerobi-cally at30,37,or39°C in Luria broth(10g l−1Difco tryptone,5g l−1Difco yeast extract,and5g l−1NaCl) containing2%(w/v)glucose or5%(w/v)arabinose. Ampicillin(50mg l−1),tetracycline(12.5mg l−1), kanamycin(50mg l−1),or chloramphenicol(40mg l−1) were added as needed.For initial tests of fermentative alanine production,strains were grown without antibiotics at37°C in NBS mineral salts medium(Causey et al.2004) supplemented with100mM ammonia sulfate,1mM betaine,and2%(w/v)glucose.Fermentation experiments (2–12%sugar)were carried out in NBS medium and AM1 medium(Martinez et al.2007).Broth was maintained at pH 7by the automatic addition of5M NH4OH.Genetic methodsStandard methods were used for genomic deoxyribonucleic acid(DNA)extraction(Qiagen,Valencia,CA),polymerase chain reaction(PCR)amplification(Stratagene,La Jolla CA,and Invitrogen,Carlsbad,CA),transformation,plas-mid extration(Qiagen),and restriction endonuclease diges-tion(New England Biolabs,Ipswich,MA).Methods for foreign gene(alaD)integration and for chromosomal gene (mgsA and dadX)deletion are described below.DNA sequencing was provided by the University of Florida Interdisciplinary Center for Biotechnology Research.The Biocyc and Metacyc databases(Karp et al.2005)were instrumental in the design and completion of these studies. Cloning the alanine dehydrogenase gene alaD from G. stearothermophilus XL-65-6and detection of the enzyme activityThe primers for amplifying alaD from G.stearothermophilus XL-65-6were designed based on the alaD sequence of G. stearothermophilus strain10.The forward primers(5′–3′GGAAAAA GGAGGAAAAAGTG ATGAAGATCGG CATT)included the ribosomal-binding region(bold)and the amino terminus(italicized).The reverse primer(5′–3′GAA GGAGTTGATCATTGTTTAACGAGAGAGG)was down-stream from the putative transcriptional terminator region (Table3).ALD was verified in clones using an activity stain (Kuroda et al.1990).E.coli TOP10F′harboring plasmids containing alaD was grown on Luria–Bertani(LB)plates at 37°C,then transferred to a Whatman7.0-cm filter paper. The filter was immersed in10mM potassium phosphate buffer(pH7.2)and incubated for20min at80°C for lysis of the cells and denaturation of the E.coli proteins.The dried filter paper was assayed in a reaction mixture containing50mM L-alanine,50mM Tris–HCl buffer (pH9.0),0.625mM NAD+,0.064mM phenazine metho-sulfate,and0.24mM nitro blue tetrazolium.The cells with ALD appeared as blue spots on the filter.Integration of alaD into E.coli SZ194The alaD gene was integrated into the chromosomal ldhA gene of SZ194.The fragment(Sma I–Kpn I,1.7kb)con-taining a tet gene flanked by two FRT sites was isolated from pLOI2065and cloned into pLOI4211between a unique Bam HI site(Klenow-treated)and Kpn I site to produce plasmid pLOI4213(6.0kb).In this plasmid,transcription of alaD and tet are oriented in the same direction.The Apa I(treated with T4DNA polymerase to produce a blunt end)–Kpn I fragment(2.2kb)containing alaD and tet was isolated from pLOI4213and cloned into pLOI2395Table2 E.coli strains and plasmids used in this studyRelevant characteristics Source or referenceStrainsSZ194plfB frd adhE ackA deletions Zhou et al.2006bXZ103-110SZ194,ldhA::FRT-tet-FRT::This studyG.stearothermophilus alaDXZ111XZ105,ldhA::G.stearothermophilus alaD This studyXZ112XZ111,metabolic evolution in NBS medium with2%glucose This studyXZ113XZ112,metabolic evolution in NBS medium with5%glucose This studyXZ115XZ113,metabolic evolution in NBS medium with8%glucose This studyXZ121XZ115,mgsA deletion This studyXZ123XZ121,metabolic evolution in NBS medium with8%glucose This studyXZ126XZ123,dadX deletion This studyXZ129XZ126,metabolic evolution in NBS medium with8%glucose This studyXZ130XZ129,metabolic evolution in AM1medium with8%glucose This studyXZ131XZ130,metabolic evolution in AM1medium with10%glucose This studyXZ132XZ131,metabolic evolution in AM1medium with12%glucose This studyPlasmidspCR2.1-TOPO bla kan;TOPO TA cloning vector InvitrogenDatsenko and Wanner2000pKD46Blaγβexo(Red recombinase),temperature conditionalpSC101repliconpFT-A Bla flp,temperature conditional pSC101replicon Posfai et al.1997pEL04cat-sacB targeting cassette Lee et al.2001;Thomason et al.2005 pLOI2224kan;R6K conditional integration vector Martinez-Morales et al.1999pLOI2065bla;FRT-tet-FRT cassette Zhou et al.2003bpLOI2395bla;ldhA franked by two Asc I site Zhou et al.2003apLOI3421 1.8kbp SmaI fragment containing aac Wood et al.2005pLOI4151bla cat;cat-sacB cassette This studyalaD integrationThis studypLOI4211bla kan alaD;alaD(PCR)from G.stearothermophilus XL-65-6cloned into pCR2.1-TOPO vectorpLOI4213bla kan;alaD-FRT-tet-FRT Kpn I-Sma I fragment(FRT-tet-FRT)This studyfrom pLOI2065cloned into Kpn I-BamH I(blunted)site of pLOI4211This studypLOI4214bla kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Apa I(blunted)-Kpn I fragment(alaD-FRT-tet-FRT)from pLOI4213cloned into ldhA at Hinc II-Kpn Isites of pLOI2395This studypLOI4215kan;ldhA’-alaD-FRT-tet-FRT-ldhA”Asc I fragment(ldhA’-alaD-FRT-tet-FRT-‘ldhA)from pLOI4214cloned into Asc I sites of pLOI2224mgsA deletionThis studypLOI4228bla kan;yccT’-mgsA-helD’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorThis studypLOI4229cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)cloned into mgsA in pLOI4228This studypLOI4230PCR fragment amplified from pLOI4228(using mgsA-1/mgsA-2primers),kinase treated,and self-ligateddadX deletionThis studypLOI4216bla kan;dadA’-dadX-cvrA’(PCR)from E.coli W clonedinto PCR2.1-TOPO vectorpLOI4218cat-sacB cassette PCR amplified from pLOI4151(Eco RV digested)This studycloned into dadX in pLOI4216This studypLOI4220PCR fragment amplified from pLOI4216(using dadX-4/dadX-5primers),kinase treated,and self-ligated(Hinc II to Kpn I sites)to produce pLOI4214(6.5kb).In this plasmid,ldhA ,alaD ,and tet genes are transcribed in the same direction.The Asc I fragment (4.3kb)containing these three genes was isolated from pLOI4214and cloned into the R6K integration vector pLOI2224to produce pLOI4215(6.2kb).Plasmid pLOI4215contains resistance genes for both tetracycline and kanamycin (Fig.2).The Asc I fragment (4.3kb)containing ldhA ,alaD ,and tet genes was isolated from pLOI4215,further cut by Xmn I to eliminate any remaining uncut plasmid DNA,and electroporated into SZ194containing the Red recombinase plasmid pKD46(Datsenko and Wanner 2000).Integrants were selected for tetracycline resistance,confirmed by sensitivity to kanamycin and ampicillin and by PCR analysis using the primers of ldhA and its neighboring genes ydbH and hslJ (Table 3).Deletion of mgsA and dadX genesA modified method for deleting E.coli chromosomal genes was developed using two steps of homologous recom-bination (Thomason et al.2005).With this method,no antibiotic genes or scar sequences remain on the chromo-some after gene deletion.In the first recombination,part of the target gene was replaced by a DNA cassette containing a chloramphenicol resistance gene (cat )and levansucrase gene (sacB ).In the second recombination,the cat –sacBcassette was removed by selection for resistance to sucrose.Cells containing the sacB gene accumulate levan during incubation with sucrose and are killed.Surviving recombi-nants are highly enriched for loss of the cat –sacB cassette.A new cassette was constructed as a template to facilitate gene deletions.The cat –sacB region was amplified from pEL04(Lee et al.2001;Thomason et al.2005)by PCR using the JM catsacB up Nhe I and JM catsacB down Nhe I primers (Table 3),digested with Nhe I,and ligated into the corresponding site in pLOI3421to produced pLOI4151.The cat –sacB cassette was amplified by PCR using pLOI4151as a template with the cat -up2and sacB -down2primers (Eco RV site included in each primer),digested with Eco RV ,and used in subsequent ligations.The mgsA gene and neighboring 500-bp regions (yccT ′–mgsA –helD ′,1,435bp)were amplified using the mgsA -up and mgsA -down primers and cloned into the pCR 2.1-TOPO vector (Invitrogen)to produce plasmid pLOI4228.A 1,000-fold diluted plasmid preparation of this plasmid served as a template for inside-out amplification using the mgsA -1and mgsA -2primers (both within the mgsA gene and facing outward).The resulting 4,958-bp fragment containing the replicon was ligated to the Eco RV-digested cat –sacB cassette from pLOI4151to produce pLOI4229(Fig.3a).This 4,958-bp fragment was also used to construct a second plasmid,pLOI4230(Fig.3b),by phosphorylation and self-ligation.In pLOI4230,the central region of mgsA is deleted (yccT ′–mgsA ′–mgsA ″–helD ′).After digestion of pLOI4229and pLOI4230with Xmn I (within the vector),each served as a template for amplifica-tion using the mgsA -up and mgsA -down primers to produce linear DNA for integration step 1(yccT ′–mgsA ′–cat –sacB –mgsA ″–helD ′)and step II (yccT ′–mgsA ′–mgsA ″–helD ′),respectively.After electroporation of the step 1fragment into XZ115containing pKD46(Red recombinase)and 2h ofTable 3Primers used in this study Primers SequencealaD -forward GGAAAAAGGAGGAAAAAGTGATGAA GATCGGCATTalaD -reverse GAAGGAGTTGATCATTGTTTAACGA GAGAGGldhA -forward AGTACCTGCAACAGGTGAAC ldhA -reverse CAGGCGACGGAATACGTCAT ldhA -up (ydbH )CTGATAACGCAGTTGCTGGA ldhA -down (hslJ )TTCATTAAATCCGCCAGCTTJM catsacB up NheI TTAGCTAGCATGTGACGGAAGATC ACTTCGJM catsacB down NheI CCGCTAGCATCAAAGGGAAAACTGT CCATATcat -up2AGAGAGGATATCTGTGACGGAAGAT CACTTCGsacB -down2AGAGAGGATATCGAATTGATCCGGT GGATGACmgsA -up CAGCTCATCAACCAGGTCAA mgsA -down AAAAGCCGTCACGTTATTGG mgsA -1AGCGTTATCTCGCGGACCGT mgsA -2AAGTGCGAGTCGTCAGTTCC dadX -up AGGCTACTCGCTGACCATTC dadX -down GGTTGTCGGTGACCAGGTAG dadX -4TGGGCTATGAGTTGATGTGC dadX -5CTGTATCGGACGGGTCATCTFig.2Integration vector used for chromosomal insertion of G.stearothermophilus alaD into E.coli ldhA .Sequence encoding the N-terminal and C-terminal regions are designated ldhA ′and ldhA ″,respectivelyincubation at 30°C to allow expression and segregation,recombinants were selected for chloramphenicol (40mg l −1)and ampicillin (50mg l −1)resistance in Luria broth at 30°C (18h).Three clones were selected,grown in Luria broth containing ampicillin and 5%(w/v)arabinose (to induce expression of red recombinase),and prepared for electro-poration.After electroporation with the step 2fragment,cells were incubated at 30°C for 4h and then transferred into a 250-ml flask containing 100ml of modified LB (100mM 3-(N -morpholino)propanesulfonic acid [MOPS]buffer added and NaCl omitted)containing 10%sucrose.After overnight incubation (30°C),clones were selected on modified LB plates (no NaCl;100mM MOPS added)containing 6%sucrose (39°C,16h).Resulting clones were tested for loss of ampicillin and chloramphenicol resistance.Construction was confirmed by PCR using the mgsA-up/down primer set.A clone containing a deletion in the central region of mgsA was selected and designated XZ121.The dadX gene was deleted in a manner analogous to that used to delete the mgsA gene.Primers for dadX deletion are shown in Table 3,and the corresponding plasmids are shown in Table 2.FermentationNBS mineral salts medium (Causey et al.2004)with 1mM betaine (Zhou et al.2006a )was used in the initial fermentation (pH 7.0).Preinoculum was grown by inocu-lating three colonies into a 250ml flask (100ml NBS medium,2%glucose,and 100mM ammonium sulfate).After 16h (37°C,120rpm),this preinoculum was diluted into 500-ml fermentation fleakers containing 300ml NBS medium (2–8%glucose,100mM ammonium sulfate,and 1mM betaine)with 33mg cell dry weight (CDW)l −1.In early experiments,pH was maintained at 7.0by automat-ically adding 2M potassium hydroxide.In later experi-ments,5M ammonium hydroxide was used to maintain pH,and a low salt medium,AM1(Martinez et al.2007),was used to replace the NBS medium for fermentation (8–12%glucose).AM1medium contains much less salt and has been optimized for E.coli .Metabolic evolutionCells from pH-controlled fermentations were serially transferred at 24-h intervals to facilitate metabolic evolution through competitive,growth-based selection (Fig.1b).At the beginning,sequentially transferred cultures were inoc-ulated with an initial density of 33mg CDW l −1.As growth increased,the inoculum was changed to a 1:100dilution and subsequently to a 1:300dilution.Periodically,clones were isolated from these experiments,assigned new strain designations,and frozen for storage.AnalysesCell mass was estimated by measuring the optical density at anic acids and glucose concentrations were mea-sured by high-performance liquid chromatography (HPLC,Underwood et al.2002).Analysis of fermentation products by mass spectroscopy and amino acid analyzer were provided by the University of Florida Interdisciplinary Center for Bio-technology Research.Alanine was found to be the predominant product.The alanine concentration and isomeric purity were further measured by HPLC using the Chiralpak MA(+)chiral column (Chiral Technologies,West Chester,PA).ResultCloning of the alanine dehydrogenase geneALD is found in Bacillus (and Geobacillus )species where it plays a pivotal role in energy generation during sporulation (Ohashima and Soda 1979;Kuroda et al.1990).ALD from B.sphaericus IFO3525has beenwidelyFig.3Plasmids used to delete mgsA .Plasmid pLOI4229(a )was used to delete the mgsA gene and insert the cat-sacB cassette in the first recombina-tion step.Plasmid pLOI4230(b )was used to remove the cat-sacB cassette to create a deletion devoid of foreign sequence.Se-quence encoding the N-terminal and C-terminal regions are des-ignated mgsA ′and mgsA ″,respectivelyused with varying degrees of success to engineer alanine production in recombinant bacteria(Uhlenbusch et al. 1991;Hols et al.1999;Lee et al.2004;Smith et al.2006). Selection of the B.sphaericus IFO3525is presumed to be due in part to the high specific activity(Ohashima and Soda 1979).In contrast,we have selected a thermostable ALD from the thermophile,G.stearothermophilus XL-65-6, based on our prior experience in expressing genes from this organism in recombinant E.coli(Burchhardt and Ingram 1992;Lai and Ingram1993;Lai and Ingram1995).The ribosomal-binding region,coding region,and tran-scriptional terminator of alaD were amplified from G. stearothermophilus XL-65-6and sequenced(EF154460in GenBank).The deduced amino acid sequence was identical to that reported for Geobacillus kaustophilus HTA426and very similar to G.stearothermophilus strain10(99%iden-tity)and G.stearothermophilus strain IFO12550(94% identity).The nucleotide sequence(65%identity)and the deduced ALD amino acid sequence(74%identity)were quite different from the B.sphaericus IFO3525gene,the gene pre-viously used for alanine production in recombinant bacteria.Modification of E.coli W for homoalanine productionE.coli W strain SZ194(pflB frdBC adhE ackA)was previously constructed to produce only D-lactic acid.All major fermentation pathways except lactate have been blocked in this strain by gene deletions(Fig.1a).To convert this strain to the production of alanine,part of the native ldhA-coding region was replaced by a DNA fragment containing the ribosomal-binding region,coding region,and transcriptional terminator of alaD from G. stearothermophilus XL-65-6.The promoterless alaD was oriented in the same direction as ldhA to allow expression from the native ldhA promoter(Fig.2).After electroporation,approximately500colonies were recovered with tetracycline resistance and sensitivity to kana-mycin,consistent with a double-crossover event.These colo-nies were further examined by PCR using ldhA forward and reverse primer set(Table3).Only eight colonies of the500 tested were correct based on an analysis of PCR fragments. These eight colonies were further verified using primer sets for alaD,ldhA forward and alaD reverse,alaD forward and ldhA reverse,and ldhA outside primers(Table3)and de-signated XZ103,XZ104,XZ105,XZ106,XZ107,XZ108, XZ109,and XZ110,respectively.These eight strains were initially tested in15-ml screw-cap tubes containing NBS medium with2%glucose and100mM ammonium sulfate, which were filled to the brim.Strain XZ105appeared to grow faster than the other strains(37°C for48h)and was selected for further development.XZ105was transformed with pFT-A,which contains an inducible flippase(FLP)recombinase(Martinez-Morales et al.1999;Posfai et al.1997).The chromosomal FRT-flanked tet gene in XZ105was removed by inducing the FLP recombinase.After growing in39°C to eliminate the temperature-sensitive plasmid pFT-A,resulting strain was designated XZ111.Expression of G.stearothermophilus alaD in XZ111is transcriptionally regulated by the ldhA promoter,the same promoter that regulates the production of lactate dehydrogenase(dominant fermentation pathway) in native E.coli.pH-controlled batch fermentation for alanine production Alanine production by strain XZ111was tested in500-ml fermentation vessels containing300ml NBS medium, 20g l−1glucose,100mM ammonium sulfate,and1mM betaine.Broth pH was automatically controlled by adding 2N potassium hydroxide.After96h,181mM alanine was produced.The alanine yield from total glucose was 81%(g/g),and84%based on glucose that had been metabo-lized.The chiral purity of L-alanine was96.1%(Table4). Very low levels of other products(lactate,succinate,ace-tate,ethanol)were present,typically below1mM.This result demonstrated that the integrated G.stearothermophilus alaD gene as a single chromosomal copy under the control of the native ldhA promoter can provide sufficient levels of ALD to support E.coli growth from the production of alanine as the sole fermentation product.Metabolic evolution of strain XZ111Although XZ111could accumulate alanine as the primary product,incubation times were long,and volumetric productivity was limited.When using a high-glucose concentration(80g l−1),growth and alanine productivity were further reduced(Table4).In this strain,adenosine triphosphate(ATP)production and growth are tightly coupled to NADH oxidation and alanine production by ALD(Fig.1b).This coupling provided a basis for strain improvement by selecting for increased growth during serial cultivation,i.e.,metabolic evolution.Cells with increased growth because of spontaneous mutations will successively displace their parents while coselecting for increased alanine productivity.Serial transfers of XZ111were carried out at24-h intervals in NBS mineral salts medium with1mM betaine.Cultures were first transferred in the medium containing20g l−1 glucose,and the pH was controlled by automatically adding 2N potassium hydroxide.However,after ten transfers to strain XZ112,little improvement was observed(data not shown).Because ammonia is essential for alanine pro-duction,it was thought that ammonia may be limiting for fermentation.Two normals potassium hydroxide containing 1N ammonia carbonate and5N ammonia hydroxide alone。
LUNA SENSATION 藻类杀菌剂数据安全表说明书
LUNA SENSATION®1/11Version 4.0 / USA Revision Date: 06/30/2020102000012886 Print Date: 06/30/2020SECTION 1: IDENTIFICATION OF THE SUBSTANCE/MIXTURE AND OF THE COMPANY/UNDERTAKINGProduct identifierTrade nameLUNA SENSATION®Product code (UVP)84469882SDS Number102000012886EPA Registration No. 264-1090Relevant identified uses of the substance or mixture and uses advised againstUseFungicideRestrictions on useSee product label for restrictions.Information on supplierSupplier Bayer CropScience LP 800 North Lindbergh Blvd. St. Louis, MO 63167 USAResponsible DepartmentEmail: ************************Emergency telephone no.Emergency Telephone Number (24hr/ 7 days)1-800-334-7577Product Information Telephone Number 1-866-99BAYER (1-866-992-2937)SECTION 2: HAZARDS IDENTIFICATIONClassification in accordance with regulation HCS 29CFR §1910.1200 Acute toxicity(Oral): Category 4Reproductive toxicity: Effects on or via lactationLabelling in accordance with regulation HCS 29CFR §1910.1200Signal word : WarningHazard statementsHarmful if swallowed.May cause harm to breast-fed children.LUNA SENSATION®2/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Precautionary statementsWash thoroughly after handling.Do not eat, drink or smoke when using this product.Obtain special instructions before use.Do not breathe mist.Avoid contact during pregnancy/ while nursing.IF SWALLOWED: Call a POISON CENTER/doctor/physician if you feel unwell.Rinse mouth.IF exposed or concerned: Get medical advice/ attention.Dispose of contents/container in accordance with local regulation.Hazards Not Otherwise Classified (HNOC)No physical hazards not otherwise classified.No health hazards not otherwise classified.SECTION 3: COMPOSITION/INFORMATION ON INGREDIENTSHazardous Component Name CAS-No.Concentration % by weight Fluopyram 658066-35-4 21.4 Trifloxystrobin 141517-21-7 21.4 SECTION 4: FIRST AID MEASURESDescription of first aid measuresGeneral advice When possible, have the product container or label with you whencalling a poison control center or doctor or going for treatment.Inhalation Move to fresh air. If person is not breathing, call 911 or an ambulance,then give artificial respiration, preferably mouth-to-mouth if possible.Call a physician or poison control center immediately.Skin contact Take off contaminated clothing and shoes immediately.Wash offimmediately with plenty of water for at least 15 minutes.Call aphysician or poison control center immediately.Eye contact Hold eye open and rinse slowly and gently with water for 15-20minutes.Remove contact lenses, if present, after the first 5 minutes,then continue rinsing eye.Call a physician or poison control centerimmediately.Ingestion Call a physician or poison control center immediately.Rinse out mouthand give water in small sips to drink.DO NOT induce vomiting unlessdirected to do so by a physician or poison control center.Never giveanything by mouth to an unconscious person.Do not leave victimunattended.Most important symptoms and effects, both acute and delayedSymptoms To date no symptoms are known.Indication of any immediate medical attention and special treatment neededLUNA SENSATION®3/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Treatment Appropriate supportive and symptomatic treatment as indicated by thepatient's condition is recommended.SECTION 5: FIREFIGHTING MEASURESExtinguishing mediaSuitable Water spray, Carbon dioxide (CO2), Alcohol-resistant foam, Sand Unsuitable High volume water jetSpecial hazards arising from the substance or mixture In the event of fire the following may be released:, Hydrogen chloride (HCl), Hydrogen cyanide (hydrocyanic acid), Hydrogen fluoride, Carbon monoxide (CO), Carbon dioxide (CO2), Nitrogen oxides (NOx)Advice for firefightersSpecial protective equipment for firefighters Firefighters should wear NIOSH approved self-contained breathing apparatus and full protective clothing.Further information Keep out of smoke. Fight fire from upwind position. Cool closedcontainers exposed to fire with water spray. Do not allow run-off fromfire fighting to enter drains or water courses.Flash point> 100 °CAuto-ignition temperature 380 °C / 716 °FLower explosion limit No data availableUpper explosion limit No data availableExplosivity Not explosive92/69/EEC, A.14 / OECD 113SECTION 6: ACCIDENTAL RELEASE MEASURESPersonal precautions, protective equipment and emergency proceduresPrecautions Keep unauthorized people away. Isolate hazard area. Avoid contactwith spilled product or contaminated surfaces.Methods and materials for containment and cleaning upMethods for cleaning up Soak up with inert absorbent material (e.g. sand, silica gel, acidbinder, universal binder, sawdust). Clean contaminated floors andobjects thoroughly, observing environmental regulations. Collect andtransfer the product into a properly labelled and tightly closedcontainer.Additional advice Use personal protective equipment. If the product is accidentallyspilled, do not allow to enter soil, waterways or waste water canal.LUNA SENSATION®4/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Reference to other sections Information regarding safe handling, see section 7.Information regarding personal protective equipment, see section 8.Information regarding waste disposal, see section 13.SECTION 7: HANDLING AND STORAGEPrecautions for safe handlingAdvice on safe handling Use only in area provided with appropriate exhaust ventilation. Handleand open container in a manner as to prevent spillage.Hygiene measures Wash hands thoroughly with soap and water after handling and beforeeating, drinking, chewing gum, using tobacco, using the toilet orapplying cosmetics.Remove Personal Protective Equipment (PPE) immediately afterhandling this product. Before removing gloves clean them with soap andwater. Remove soiled clothing immediately and clean thoroughly beforeusing again. Wash thoroughly with soap and water after handling. Conditions for safe storage, including any incompatibilitiesRequirements for storage areas and containers Store in a cool, dry place and in such a manner as to prevent cross contamination with other crop protection products, fertilizers, food, and feed. Store in original container and out of the reach of children, preferably in a locked storage area. Protect from freezing. Keep away from direct sunlight.SECTION 8: EXPOSURE CONTROLS/PERSONAL PROTECTIONControl parameters*OES BCS: Internal Bayer AG, Crop Science Division "Occupational Exposure Standard"Exposure controlsPersonal protective equipmentIn normal use and handling conditions please refer to the label and/or leaflet. In all other cases the following recommendations would apply.Respiratory protection When respirators are required, select NIOSH approved equipmentbased on actual or potential airborne concentrations and inaccordance with the appropriate regulatory standards and/or industryrecommendations.Hand protection Chemical resistant nitrile rubber glovesEye protection Safety glasses with side-shieldsLUNA SENSATION®5/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Skin and body protection Wear long-sleeved shirt and long pants and shoes plus socks. General protective measures Follow manufacturer's instructions for cleaning/maintaining PPE. Ifno such instructions for washables, use detergent and warm/tepidwater.Keep and wash PPE separately from other laundry.SECTION 9. PHYSICAL AND CHEMICAL PROPERTIESAppearance white to beigePhysical State suspensionOdor characteristicOdour Threshold No data availablepH 5.0 - 8.0 (100 %) (23 °C)Viscosity, kinematic No data availableVapor Pressure No data availableVapor Density (Air = 1)No data availableDensity ca. 1.17 g/cm³ (20 °C)Evaporation rate No data availableBoiling Point No data availableMelting / Freezing Point No data availableWater solubility suspensiveMinimum Ignition Energy Not applicableDecompositionStable under normal conditions.temperatureSelf-accelaratingNo data availabledecomposition temperature(SADT)Partition coefficient: n-Not applicableoctanol/waterViscosity240 - 350 mPa.s (20 °C) Velocity gradient 20 /sFlammability No data availableOxidizing properties No oxidizing propertiesFlash point> 100 °CAuto-ignition temperature 380 °C / 716 °FLower explosion limit No data availableUpper explosion limit No data availableLUNA SENSATION®6/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Explosivity Not explosive92/69/EEC, A.14 / OECD 113Particle size No data availableOther information Further safety related physical-chemical data are not known.SECTION 10: STABILITY AND REACTIVITYReactivityThermal decomposition Stable under normal conditions.Chemical stability Stable under recommended storage conditions.Possibility of hazardous reactions No hazardous reactions when stored and handled according to prescribed instructions.Conditions to avoid Extremes of temperature and direct sunlight.Incompatible materials No incompatible materials known.Hazardous decompositionproductsNo decomposition products expected under normal conditions of use. SECTION 11: TOXICOLOGICAL INFORMATIONExposure routes Skin Absorption, Ingestion, Inhalation, Eye contactImmediate EffectsSkin Harmful if absorbed through skin.Ingestion Harmful if swallowed.Inhalation Harmful if inhaled.Information on toxicological effectsAcute oral toxicity LD50 (female Rat) 2,000 mg/kgAcute inhalation toxicity LC50 (Rat) > 1.7 mg/lExposure time: 4 hDetermined in the form of liquid aerosol.Highest attainable concentration.No deathsAcute dermal toxicity LD50 (Rat) > 2,000 mg/kgSkin corrosion/irritation No skin irritation (Rabbit)Serious eye damage/eyeirritationNo eye irritation (Rabbit)LUNA SENSATION®7/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020Respiratory or skin sensitisation Skin: Non-sensitizing. (Mouse)OECD Test Guideline 429, local lymph node assay (LLNA)Assessment STOT Specific target organ toxicity – single exposureFluopyram: Based on available data, the classification criteria are not met.Trifloxystrobin: Based on available data, the classification criteria are not met.Assessment STOT Specific target organ toxicity – repeated exposureFluopyram did not cause specific target organ toxicity in experimental animal studies.Trifloxystrobin did not cause specific target organ toxicity in experimental animal studies.Assessment mutagenicityFluopyram was not mutagenic or genotoxic in a battery of in vitro and in vivo tests.Trifloxystrobin was not mutagenic or genotoxic in a battery of in vitro and in vivo tests.Assessment carcinogenicityFluopyram caused at high dose levels an increased incidence of tumours in rats in the followingorgan(s): Liver.Fluopyram caused at high dose levels an increased incidence of tumours in mice in the followingorgan(s): Thyroid.The tumours seen with Fluopyram were caused through a non-genotoxic mechanism, which is not relevant at low doses. The mechanism that triggers these tumours is not relevant to humans. Trifloxystrobin was not carcinogenic in lifetime feeding studies in rats and mice.ACGIHNone.NTPNone.IARCNone.OSHANone.Assessment toxicity to reproductionFluopyram caused reproduction toxicity in a two-generation study in rats only at dose levels also toxic to the parent animals. The reproduction toxicity seen with Fluopyram is related to parental toxicity. Trifloxystrobin caused reduced body weight development in offspring during lactation only at doses also producing systemic toxicity in adult rats.Assessment developmental toxicityFluopyram caused developmental toxicity only at dose levels toxic to the dams. The developmental effects seen with Fluopyram are related to maternal toxicity.Trifloxystrobin caused developmental toxicity only at dose levels toxic to the dams. The developmental effects seen with Trifloxystrobin are related to maternal toxicity.Aspiration hazardBased on available data, the classification criteria are not met.LUNA SENSATION®8/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Further informationOnly acute toxicity studies have been performed on the formulated product.The non-acute information pertains to the active ingredient(s).SECTION 12: ECOLOGICAL INFORMATIONToxicity to fish LC50 (Oncorhynchus mykiss (rainbow trout)) 0.091 mg/lExposure time: 96 hToxicity to aquatic invertebratesEC50 (Daphnia magna (Water flea)) 0.086 mg/lExposure time: 48 hLC50 (Mysidopsis bahia (mysid shrimp)) 0.00862 mg/l Exposure time: 96 hThe value mentioned relates to the active ingredient trifloxystrobin.Toxicity to aquatic plants IC50 (Raphidocelis subcapitata (freshwater green alga)) 0.292 mg/lGrowth rate; Exposure time: 72 hEC10 (Desmodesmus subspicatus (green algae)) 0.0025 mg/lGrowth rate; Exposure time: 72 hThe value mentioned relates to the active ingredient trifloxystrobin. Biodegradability Fluopyram:Not rapidly biodegradableTrifloxystrobin:Not rapidly biodegradableKoc Fluopyram: Koc: 279Trifloxystrobin: Koc: 2377Bioaccumulation Fluopyram: Bioconcentration factor (BCF) 18Does not bioaccumulate.Trifloxystrobin: Bioconcentration factor (BCF) 431Does not bioaccumulate.Mobility in soil Fluopyram: Moderately mobile in soilsTrifloxystrobin: Slightly mobile in soilsAdditional ecologicalinformationNo other effects to be mentioned.Environmental precautions Do not apply directly to water, to areas where surface water is presentor to intertidal areas below the mean high water mark.Drift and runoff from treated areas may be hazardous to aquaticorganisms in adjacent sites.Do not apply when weather conditions favor runoff or drift.Do not allow product to enter streams, sewers or other waterways.Do not contaminate surface or ground water by cleaning equipment ordisposal of wastes, including equipment wash water.Apply this product as specified on the label.LUNA SENSATION®9/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 SECTION 13: DISPOSAL CONSIDERATIONSWaste treatment methodsProduct Dispose in accordance with all local, state/provincial and federalregulations.Pesticide, spray mixture or rinse water that cannot be used according tolabel instructions may be disposed of on site or at an approved wastedisposal facility.Follow advice on product label and/or leaflet.Contaminated packaging Do not re-use empty containers.Triple rinse containers.Completely empty container into application equipment, then dispose ofempty container in a sanitary landfill, by incineration or by otherprocedures approved by state/provincial and local authorities.If burned, stay out of smoke.Follow advice on product label and/or leaflet.RCRA Information Characterization and proper disposal of this material as a special orhazardous waste is dependent upon Federal, State and local laws andare the user's responsibility. RCRA classification may apply.SECTION 14: TRANSPORT INFORMATION49CFR Not dangerous goods / not hazardous materialIMDGUN number 3082Class 9Packaging group IIIMarine pollutant YESProper shipping name ENVIRONMENTALLY HAZARDOUS SUBSTANCE, LIQUID,N.O.S.(TRIFLOXYSTROBIN SOLUTION)IATAUN number 3082Class 9Packaging group IIIEnvironm. Hazardous Mark YESProper shipping name ENVIRONMENTALLY HAZARDOUS SUBSTANCE, LIQUID,N.O.S.(TRIFLOXYSTROBIN SOLUTION )This transportation information is not intended to convey all specific regulatory information relating to this product. It does not address regulatory variations due to package size or special transportation requirements.LUNA SENSATION®10/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 Freight Classification: INSECTICIDES OR FUNGICIDES, N.O.I., OTHER THANPOISONSECTION 15: REGULATORY INFORMATIONEPA Registration No.264-1090US Federal RegulationsTSCA listWater 7732-18-51,2-Propanediol 57-55-6Polyethylene-polypropylene copolymer 9003-11-6US. Toxic Substances Control Act (TSCA) Section 12(b) Export Notification (40 CFR 707, Subpt D) No export notification needs to be made.SARA Title III - Section 302 - Notification and InformationNot applicable.SARA Title III - Section 313 - Toxic Chemical Release ReportingNone.US States Regulatory ReportingCA Prop65This product does not contain any substances known to the State of California to cause cancer.This product does not contain any substances known to the State of California to causereproductive harm.US State Right-To-Know Ingredients1,2-Propanediol 57-55-6 MN, RINone.EPA/FIFRA Information:This chemical is a pesticide product registered by the Environmental Protection Agency and is subject to certain labeling requirements under federal pesticide law. These requirements differ from the classification criteria and hazard information required for safety data sheets, and for workplace labels of non-pesticide chemicals. Following is the hazard information required on the pesticide label:Signal word:Caution!Hazard statements:Harmful if swallowed, inhaled or absorbed through the skin.Avoid contact with skin, eyes and clothing.Avoid inhalation of vapour or mist.SAFETY DATA SHEETLUNA SENSATION®11/11 Version 4.0/USA Revision Date: 06/30/2020 102000012886Print Date: 06/30/2020 SECTION 16: OTHER INFORMATIONAbbreviations and acronyms49CFR Code of Federal Regulations, Title 49ACGIH US. ACGIH Threshold Limit ValuesATE Acute toxicity estimateCAS-Nr. Chemical Abstracts Service numberCERCLA Comprehensive Environmental Response, Compensation, and Liability Act EINECS European inventory of existing commercial substancesELINCS European list of notified chemical substancesIARC International Agency for Research on CancerIATA International Air Transport AssociationIMDG International Maritime Dangerous GoodsN.O.S. Not otherwise specifiedNTP US. National Toxicology Program (NTP) Report on CarcinogensOECD Organization for Economic Co-operation and DevelopmentTDG Transportation of Dangerous GoodsTWA Time weighted averageUN United NationsWHO World health organisationNFPA 704 (National Fire Protection Association):Health - 2 Flammability - 1 Instability - 0 Others - noneHMIS (Hazardous Materials Identification System, based on the Third Edition Ratings Guide) Health - 2 Flammability - 1 Physical Hazard - 0 PPE -0 = minimal hazard, 1 = slight hazard, 2 = moderate hazard, 3 = severe hazard, 4 = extreme hazard Reason for Revision: The following sections have been revised: Section 2: Hazards Identification. Section 3: Composition / Information on Ingredients. Section 11: Toxicological Information. Section 12. Ecological information. Reviewed and updated for general editorial purposes.Revision Date: 06/30/2020This information is provided in good faith but without express or implied warranty. The customer assumes all responsibility for safety and use not in accordance with label instructions. The product names are registered trademarks of Bayer.。
Leonurine_hydrochloride_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Leonurine (hydrochloride)Catalog No. :HY-N0741ACAS No. :24735-18-01.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:SCM⁻198 hydrochloride; SCM198 hydrochloride; SCM 198 hydrochlorideFormula:C14H22ClN3O5Molecular Weight:347.79CAS No. :24735-18-04. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
盐酸萘替芬溶液说明
盐酸萘替芬溶液说明书【药品名称】通用名：盐酸萘替芬溶液曾用名：商品名：英文名：Naftifine Hydrochloride Solution汉语拼音：YɑnsuɑnnɑitifenRonɡye本品主要成份为：盐酸萘替芬。
其化学名称为：结构式：分子式：分子量：【性状】【药理毒理】本品为一新型丙烯胺类局部抗真菌药。
对皮肤真菌（毛癣菌属、小孢子菌属、表皮癣菌属）有杀菌作用，对马拉色菌属、念珠菌属及其他酵母菌具有抑菌作用。
对革兰阳性及阴性细菌也具有局部杀菌作用。
其作用机制为抑制真菌角鲨烯、环氧化酶，干扰真菌细胞麦角固醇的生物合成，影响真菌的脂质代谢，使真菌细胞损伤和死亡而起到杀菌和抑菌作用。
【药代动力学】健康人皮肤外用后约有3%～6%的剂量被吸收。
单剂量给药24小时内在皮肤表层的萘替芬浓度足以抑制皮肤癣菌的生长。
萘替芬在体内通过苯环和萘环氧化以及N-去烷基化，至少可转化成三种代谢物。
体内药物约有40%～60%以原形和代谢物形式排泄到尿中，其余部分经胆汁排泄到粪便中。
皮肤外用萘替芬的半衰期约为2～3天。
【适应症】适用于敏感真菌所引起的皮肤真菌病如体股癣、手足癣、头癣、甲癣、花斑癣、浅表念珠菌病以及皮肤皱褶部的擦烂性真菌病。
【用法用量】外用：涂抹患处，病损表面及四周约2.5cm宽的正常皮肤均应涂敷，用量为一日1次。
疗程随病种及病变部位有所不同，一般2～4周，严重者可用到8周，甲癣需用6个月。
为预防复发，体征消失后可继续用药2周。
【不良反应】不良反应罕见，少数患者有局部刺激，如红斑、烧灼及干燥、瘙痒等感觉，个别患者可发生接触性皮炎，无全身不良反应。
【注意事项】（1）本品仅供外用。
（2）不宜用于眼部及粘膜部位、急性炎症部位及开放性损伤部位。
（3）连续用药4周后如症状无改善请再到医院就诊。
【孕妇及哺乳期妇女用药】动物实验资料表明外用于皮肤可吸收分布于乳汁中，故对哺乳期妇女慎用。
孕妇用药资料不详。
【儿童用药】尚不知本品对儿童的安全性和有效性。
lord 公司的水溶液性胶合剂 CHEMLOK 8560D 安全数据表 说明书
USA SAFETY DATA SHEET1. CHEMICAL PRODUCT AND COMPANY IDENTIFICATIONProduct name:CHEMLOK 8560DProduct Use/Class: Aqueous AdhesiveLORD Corporation111 LORD DriveCary, NC 27511-7923 USATelephone: 814 868-3180Non-Transportation Emergency: 814 763-2345Chemtrec 24 Hr Transportation Emergency No.800 424-9300 (Outside Continental U.S. 703 527-3887)EFFECTIVE DATE: 06/30/20212. HAZARDS IDENTIFICATIONGHS CLASSIFICATION:Serious eye damage/eye irritation Category 2ASkin sensitization Category 1ACarcinogenicity Category 2Specific target organ systemic toxicity (single exposure) Category 2 blood systemSpecific target organ systemic toxicity (single exposure) Category 1 Respiratory system, Systemic toxicity Specific target organ systemic toxicity (repeated exposure) Category 2 blood systemSpecific target organ systemic toxicity (repeated exposure) Category 1 LungsHazardous to the aquatic environment - acute hazard Category 2Hazardous to the aquatic environment - chronic hazard Category 2GHS LABEL ELEMENTS:Symbol(s)Signal WordD ANGERHazard StatementsCauses serious eye irritation.May cause an allergic skin reaction.Suspected of causing cancer.May cause damage to organs.(blood system)Causes damage to organs.(Respiratory system, Systemic toxicity)May cause damage to organs through prolonged or repeated exposure.(blood system)Causes damage to organs through prolonged or repeated exposure.(Lungs)Toxic to aquatic life.Toxic to aquatic life with long lasting effects.Precautionary StatementsPreventionObtain special instructions before use.Do not handle until all safety precautions have been read and understood.Wear protective gloves/eye protection/face protection.Use personal protective equipment as required.Do not breathe dust/fume/gas/mist/vapors/spray.Wash thoroughly after handling.300000005458Do not eat, drink or smoke when using this product.Contaminated work clothing should not be allowed out of the workplace.Avoid release to the environment.ResponseGet medical advice/attention if you feel unwell.IF exposed: Call a POISON CENTER or doctor/physician.Specific treatment (see supplemental first aid instructions on this label).IF ON SKIN: Wash with plenty of soap and water.If skin irritation or rash occurs: Get medical advice/attention.IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do.Continue rinsing.If eye irritation persists: Get medical advice/attention.Wash contaminated clothing before reuse.Collect spillage.StorageStore locked up.Disposal:Dispose of contents/container in accordance with waste/disposal laws and regulations of your country or particular locality.Other Hazards:This product contains component(s) which have the following warnings; however based on the GHS classification criteria of your country or locale, the product mixture may be outside the respective category(s).Acute: In elevated-temperature applications, product may release vapors that may produce cyanosis in the absence of sufficient ventilation or adequate respiratory protection. May be harmful if swallowed. Ingestion is not an expected route of entry in industrial or commercial uses. This product contains a residual amount of a chemical substance that may cause an allergic skin and/or respiratory reaction.Causes mild skin irritation.Chronic: Prolonged or repeated contact may result in dermatitis. The nitrogen substituted aromatic in this product gave positive results for mutagenicity in an Ames Assay study while two other mutagenicity studies proved negative.IARC has identified the proprietary curative in this product as an "animal suspected" carcinogen, Group 3, which downgrades a previous NCI report of it as an "animal positive" carcinogen. IARC has designated carbon black as Group 2B - inadequate evidence for carcinogenicity in humans, but sufficient evidence in experimental animals. In 2006 IARC reaffirmed its 1995 finding that there is "inadequate evidence" from human health studies to assesswhether carbon black causes cancer in humans. Further, epidemiological evidence from well-conductedinvestigations has shown no causative link between carbon black exposure and the risk of malignant or non-malignant respiratory disease in humans.withheld.The above Nonylphenol ethoxylate compound is listed by ECHA as an SVHC.FIRST AID - EYE CONTACT: Flush eyes immediately with large amount of water for at least 15 minutes holding eyelids open while flushing. Get prompt medical attention.FIRST AID - SKIN CONTACT: Flush contaminated skin with large amounts of water while removing contaminated clothing. Wash affected skin areas with soap and water. Get medical attention if symptoms occur.FIRST AID - INHALATION: Move person to fresh air. Restore and support continued breathing. If breathing is difficult, give oxygen. Get immediate medical attention.FIRST AID - INGESTION: If swallowed, do not induce vomiting. Call a physician or poison control center immediately for further instructions. Never give anything by mouth if victim is rapidly losing consciousness, unconscious or convulsing.SUITABLE EXTINGUISHING MEDIA: Carbon Dioxide, Dry Chemical, Foam, Water FogUNSUITABLE EXTINGUISHING MEDIA: Not determined for this product.SPECIFIC HAZARDS POSSIBLY ARISING FROM THE CHEMICAL: Keep containers tightly closed. Closed containers may rupture when exposed to extreme heat. Use water spray to keep fire exposed containers cool. WARNING: Due to the combustible nature of the dried film of this product and the potential for smoldering or fire, the accumulation and buildup of the dried film on spray booth walls and floors, spindles, fixtures and other surfaces should be avoided, and any buildup should be removed. Keep the dried film accumulations away from sparks, friction, impact, high heat (>235 F/>112 C) or other sources of ignition. These conditions could cause the dried film to ignite very readily and quickly, and the resulting smoldering or fire may be difficult to extinguish. During removal of accumulation/buildup of this product, take precautions to avoid heat, friction and impact during the cleaning process. Use paint stripper, brass brush, or plastic scraper for cleaning. In the event of smoldering or a fire involving the dried product, Cold Fire®** fire suppressing agent is preferred as the extinguishing medium. If Cold Fire® is not available, use water spray as the extinguishing medium. Take efforts to ensure that these agents reach the base of the smoldering or fire. Parker-LORD Corporation will not be responsible for personal injuries, property damage or any other damages arising from the accumulation (buildup, cleaning/removal or any related smoldering or fire) resulting from the use of this product. Refer to the Chemlok® Safe Handling Guide for additional information. **NOTE: Parker-LORD Corporation has determined Cold Fire® fire suppressing agent to be effective in extinguishing fires involving dried Chemlok® adhesives. Parker-LORD does not recommend any particular equipment or system for use in delivering or applying Cold Fire® products. Customer is responsible for determining that Cold Fire® products and any delivery equipment or system is appropriate and effective for customer's specific needs. During a fire, irritating and/or toxic gases and particulate may be generated by thermal decomposition or combustion.SPECIAL PROTECTIVE EQUIPMENT AND PRECAUTIONS FOR FIRE-FIGHTERS: Wear full firefighting protective clothing, including self-contained breathing apparatus (SCBA). If water is used, fog nozzles are preferable.PERSONAL PRECAUTIONS, PROTECTIVE EQUIPMENT AND EMERGENCY PROCEDURES: Avoid breathing vapors. Avoid contact. Use appropriate respiratory protection for large spills or spills in confined area.ENVIRONMENTAL PRECAUTIONS: Do not contaminate bodies of water, waterways, or ditches, with chemical or used container.METHODS AND MATERIALS FOR CONTAINMENT AND CLEANUP: Notify appropriate authorities if necessary. Contain and remove with inert absorbent material. Avoid contact. Keep non-essential personnel away from spill area. Before attempting cleanup, refer to hazard caution information in other sections of the SDS form.HANDLING: Keep closure tight and container upright to prevent leakage. Avoid skin and eye contact. Wash thoroughly after handling. Do not handle until all safety precautions have been read and understood. Empty containers should not be re-used. Use with adequate ventilation.STORAGE: Store only in well-ventilated areas. Keep from freezing. Keep container closed when not in use.INCOMPATIBILITY: Strong acids, bases, and strong oxidizers.Engineering controls: Sufficient ventilation in pattern and volume should be provided in order to maintain air contaminant levels below recommended exposure limits.PERSONAL PROTECTION MEASURES/EQUIPMENT:RESPIRATORY PROTECTION: Use a NIOSH approved chemical/mechanical filter respirator designed to remove a combination of particulates and organic vapor if occupational limits are exceeded. For emergencysituations, confined space use, or other conditions where exposure limits may be greatly exceeded, use an approved air-supplied respirator. For respirator use observe OSHA regulations (29CFR 1910.134) or use in accordance with applicable laws and regulations of your country or particular locality.SKIN PROTECTION: Use neoprene, nitrile, or rubber gloves to prevent skin contact.EYE PROTECTION: Use safety eyewear including safety glasses with side shields and chemical goggles where splashing may occur.OTHER PROTECTIVE EQUIPMENT: Remove and wash contaminated clothing before reuse.HYGIENIC PRACTICES: Wash hands before eating, smoking, or using toilet facility. Do not smoke in any chemical handling or storage area. Food or beverages should not be consumed anywhere this product is handled or stored. Wash thoroughly after handling.Typical values, not to be used for specification purposes.ODOR: Odorless VAPOR PRESSURE: N.D.APPEARANCE: Green/Black VAPOR DENSITY: Heavier than Air PHYSICAL STATE: Liquid LOWER EXPLOSIVE LIMIT: Not ApplicableUPPER EXPLOSIVE LIMIT: Not ApplicableFLASH POINT:≥ 201 °F, 93 °CSetaflash Closed CupBOILING RANGE: 100 °C EVAPORATION RATE: Slower than n-butyl-acetate AUTOIGNITION TEMPERATURE:N.D.DENSITY: 1.18 g/cm3 (9.83 lb/gal) DECOMPOSITION TEMPERATURE:N.D. VISCOSITY, DYNAMIC: N.D.ODOR THRESHOLD: N.D.VISCOSITY, KINEMATIC: N.D.SOLUBILITY IN H2O: Soluble VOLATILE BY WEIGHT: 52.14 %pH: 6.0VOLATILE BY VOLUME: 61.54 %FREEZE POINT: N.D. VOC CALCULATED: 0.02 lb/gal, 3 g/l COEFFICIENT OF WATER/OILN.D.DISTRIBUTION:LEGEND: N.A. - Not Applicable, N.E. - Not Established, N.D. - Not DeterminedHAZARDOUS POLYMERIZATION: Hazardous polymerization will not occur under normal conditions.STABILITY: Product is stable under normal storage conditions.CONDITIONS TO AVOID: High temperatures.; For dried product issues, refer to Section 5 of the (M)SDS. INCOMPATIBILITY: Strong acids, bases, and strong oxidizers.HAZARDOUS DECOMPOSITION PRODUCTS: Decomposition due to high temperatures or a fire causes the formation of irritating and/or toxic gases, organic vapors or fumes., May contain CO, CO2, oxides of nitrogen, oxides of sulfur, halogenated by-products, Metal oxidesEXPOSURE PATH: Refer to section 2 of this SDS.SYMPTOMS:Refer to section 2 of this SDS.TOXICITY MEASURES:Germ cell mutagenicity: No classification proposedCarcinogenicity: Category 2 - Suspected of causing cancer.Components contributing to classification: Curative.Reproductive toxicity: No classification proposedPERSISTENCE AND DEGRADABILITY:Not determined for this product.BIOACCUMULATIVE: Not determined for this product.MOBILITY IN SOIL: Not determined for this product.OTHER ADVERSE EFFECTS: Not determined for this product.DISPOSAL METHOD: Disposal should be done in accordance with Federal (40CFR Part 261), state and local environmental control regulations. If waste is determined to be hazardous, use licensed hazardous waste transporter and disposal facility. Waste streams, including the dried adhesive residue, resulting from the use of this product should be tested for RCRA characteristics, including ignitability, to determine any applicable waste classifications.US DOT RoadProper Shipping Name: Environmentally hazardous substances, liquid, n.o.s.Hazard Class: 9SECONDARY HAZARD: NoneUN/NA Number: 3082Packing Group: IIIEmergency Response Guide Number: 171For US DOT non-bulk road shipments this material may be classified as NOT REGULATED. For the mostaccurate shipping information, refer to your transportation/compliance department regarding changes inpackage size, mode of shipment or other regulatory descriptors.IATA CargoPROPER SHIPPING NAME: Environmentally hazardous substance, liquid, n.o.s.Hazard Class: 9HAZARD CLASS: NoneUN NUMBER: 3082PACKING GROUP: IIIEMS: 9LIMDGPROPER SHIPPING NAME: Environmentally hazardous substance, liquid, n.o.s.Hazard Class: 9HAZARD CLASS: NoneUN NUMBER: 3082PACKING GROUP: IIIEMS: F-AThe listed transportation classification applies to non-bulk shipments. It does not address regulatory variations due to changes in package size, mode of shipment or other regulatory descriptors. For the most accurate shipping information, refer to your transportation/compliance department.U.S. FEDERAL REGULATIONS: AS FOLLOWS:SARA SECTION 313This product contains the following substances subject to the reporting requirements of Section 313 of Title III of the Superfund Amendment and Reauthorization Act of 1986 and 40 CFR part 372.:Chemical Name CAS Number Weight % Less ThanZinc compound PROPRIETARY10.0%TOXIC SUBSTANCES CONTROL ACT:INVENTORY STATUSThe chemical substances in this product are on the active TSCA Section 8 Inventory or exempt.EXPORT NOTIFICATIONThis product contains the following chemical substances subject to the reporting requirements of TSCA 12(B) if exported from the United States:NoneUnder HazCom 2012 it is optional to continue using the HMIS rating system. It is important to ensure employees have been trained to recognize the different numeric ratings associated with the HazCom 2012 and HMIS schemes.HMIS RATINGS - HEALTH: 2* FLAMMABILITY: 1 PHYSICAL HAZARD: 0* - Indicates a chronic hazard; see Section 2Revision: Company LogoEffective Date: 06/30/2021The information contained herein is, to the best of our knowledge and belief, accurate. However, since the conditions of handling and use are beyond our control, we make no guarantee of results, and assume no liability for damages incurred by use of this material. It is the responsibility of the user to comply with all applicable federal, state and local laws and regulations.。
雷德诺水溶氧化氢抗溅液-精品（乳胶）安全数据表说明书
P280 P264
Wear protective gloves, protective clothing,eye protection,face protection. Wash face, hands and any exposed skin thoroughly after handling.
P210 Keep away from heat, sparks, open flames, hot surfaces - No smoking.
111-42-2
ETHYLENE OXIDE
75-21-8
*The exact percentage (concentration) of composition has been withheld as a trade secret.
Weight %* 10-20 1-10 <1
<0.0001
March 23, 2019
Section 3: Composition and Information on Ingredients
SUBSTANCES:
Chemical Name
CAS-No
DIMETHYLETHER
115-10-6
NONYLPHENOXYPOLYETHOXYETHANOL
127087-87-0
DIETHANOLAMINE
Radnor Water Based Anti-Spatter - Premium (Aerosol)
Anti-Spatter Prevents Spatter Build Up in Welding Operations 64000111 042R Radnor 259 North Radnor - Chester Road - Suite 100 Radnor, PA, 19087-5283 866-734-3438 March 23 Regulated Hazardous / Regulated
息痛卡因注射剂1%
息痛卡因®注射劑1％息痛卡因注射劑1％ 本藥限由醫師使用衛署藥輸字第022080號Xylocaine® Injection 1%Lidocaine hydrochloride[產品資訊]可產生局部或區域性麻醉作用之注射液。
[藥名]XYLOCAINE®之活性成份為lidocaine hydrochloride。
Lidocaine hydrochloride (AAN)之CAS號碼為 6108‐05‐0。
而lidocaine hydrochloride anhydrous之CAS號碼為73‐78‐9。
Lidocaine hydrochloride 之化學名為2‐Diethylaminoaceto‐2', 6'‐xylidide。
其在澳洲核准之名稱為lignocaine hydrochloride。
Lidocaine 之化學構造為：性狀Lidocaine被分類為細胞膜穩定劑，為一種胺類局部麻醉劑；性質極為安定，且其單方溶液可用高壓高溫方式滅菌，若需要時最多可再重複滅菌兩次。
Lidocaine hydrochloride單方溶液為無菌、等張之溶液，含有Lidocaine hydrochloride 、調整pH值之sodium chloride/ sodium hydroxide及注射用水。
息痛卡因溶液不含抗菌劑，因此只能使用一次並將剩餘藥品丟棄。
Lidocaine hydrochloride單方溶液pH值約為5.0‐7.0。
Lidocaine鹽基之pKa值為7.85（25℃）；油/水分佈係數為2.9；分子量為234.3。
[藥理學]如同其他局部麻醉劑，Lidocaine可藉由防止鈉離子穿越神經膜向內移動，而可逆地阻止神經衝動沿著神經纖維傳導。
醯胺類 (amide) 局部麻醉劑被認為是在神經膜內的鈉離子管道作用。
局部麻醉劑對於腦部及心肌內可激發之細胞膜 (excitable membrane) 可能有相似的作用。
依地酸二钠美国药典34版标准
Edetate Disodium(ed' e tate dye soe' dee um).C10H14N2Na2O8·2H2O 372.24Glycine, N,N¢-1,2-ethanediylbis[N-(carboxymethyl)-, disodium salt, dihydrate.Disodium (ethylenedinitrilo)tetraacetate dihydrate [6381-92-6].Anhydrous 336.21 [139-33-3].» Edetate Disodium contains not less than 99.0 percent and not more than 101.0 percent of C10H14N2Na2O8, calculated on the dried basis.Packaging and storage— Preserve in well-closed containers.USP Reference standards 11—USP Edetate Disodium RSIdentification—A: Infrared Absorption 197K: undried.B: To 5 mL of water in a test tube add 2 drops of ammonium thiocyanate TS and 2 drops of ferric chloride TS, and mix. To the deep red solution add about 50 mg of Edetate Disodium, and mix: the red color is discharged, leaving a yellowish solution.C: It responds to the flame test for Sodium 191.pH 791: between 4.0 and 6.0, in a solution (1 in 20).Loss on drying 731— Dry it at 150 for 6 hours: it loses not less than 8.7% and not more than 11.4% of its weight.Calc ium—To a solution (1 in 20) add 2 drops of methyl red TS, and neutralize with 6 N ammonium hydroxide. Add 3 N hydrochloric acid dropwise until the solution is just acid, and then add 1 mL of ammonium oxalate TS: no precipitate is formed.Heavy metals, Method II 231: 0.005%.Limit of nitrilotriacetic acid—Mobile phase— Add 10 mL of 1.0 M tetrabutylammonium hydroxide in methanol to 200 mL of water, and adjust with 1 M phosphoric acid to a pH of 7.5 ±0.1. Transfer the solution so obtained to a 1000-mL volumetric flask, add 90 mL of methanol, dilute with water to volume, mix, pass through a filter having a 0.5-µm or finer porosity, and degas.Cupric nitrate solution—Prepare a solution containing about 10 mg of cupric nitrate(Cu(NO3)2) per mL.Standard stock solution— Transfer about 100 mg of nitrilotriacetic acid, accurately weighed, to a 10-mL volumetric flask, add 0.5 mL of ammonium hydroxide, and mix. Dilute with water to volume, and mix.Resolution solution—Transfer 10 mg of Edetate Disodium to a 100-mL volumetric flask, add 100 µL of Standard stock solution, dilute with Cupric nitrate solution to volume, and mix. Sonicate, if necessary, to dissolve.Standard solution— Transfer 1.0 g of Edetate Disodium to a 100-mL volumetric flask, add 100 µL of Standard stock solution, dilute with Cupric nitrate solution to volume, and mix. Sonicate, if necessary, to dissolve.Test solution— Transfer 1.0 g of Edetate Disodium to a 100-mL volumetric flask, dilute with Cupric nitrate solution to volume, and mix. Sonicate, if necessary, to dissolve.Chromatographic system (see Chromatography 621)— The chromatograph is equipped witha 254-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about2 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.35 for nitrilotriacetic acid, 0.65 for copper, and 1.0 for edetate; and the resolution, R, between nitrilotriacetic acid and copper is not less than 3. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The response of the nitrilotriacetic acid peak obtained from the Test solution does not exceed the difference between the nitrilotriacetic acid peak responses obtained from the Standard solution and the Test solution: not more than 0.1% of nitrilotriacetic acid is found.Assay—Assay preparation— Dissolve about 5 g of Edetate Disodium, accurately weighed, in about 100 mL of water contained in a 250-mL volumetric flask, add water to volume, and mix.Procedure— Place about 200 mg of chelometric standard calcium carbonate, previously dried at 110 for 2 hours, cooled in a desiccator, and accurately weighed, in a 400-mL beaker, add 10 mL of water, and swirl to form a slurry. Cover the beaker with a watch glass, and without removingthe latter, add 2 mL of 3 N hydrochloric acid from a pipet. Swirl the contents of the beaker, and dissolve the calcium carbonate. Wash down the sides of the beaker, the outer surface of the pipet, and the watch glass with water, and dilute with water to about 100 mL. While stirring the solution, preferably with a magnetic stirrer, add about 30 mL of the Assay preparation from a 50-mL buret. Add 15 mL of 1 N sodium hydroxide and 0.30 g of hydroxy naphthol blue, and continue the titration with the Assay preparation to a blue endpoint. Calculate the weight, in mg, of C10H14N2Na2O8 in the portion of Edetate Disodium taken by the formula:(336.21/100.09)W(VT /V)in which 336.21 and 100.09 are the molecular weights of edetate disodium and calcium carbonate, respectively; W is the weight, in mg, of calcium carbonate; VT is the volume, in mL, of the Assay preparation; and V is the volume, in mL, of the Assay preparation consumed in the titration.Auxiliary Information— Please check for your question in the FAQs before contacting USP.Topic/Question Contact Expert CommitteeMonograph Elena Gonikberg, Ph.D.Principal Scientific Liaison1-301-816-8251 (SM32010) Monographs - Small Molecules 3Reference Standards RS Technical Services1-301-816-8129**************USP34–NF29 Page 2663Pharmacopeial Forum: V olume No. 32(4) Page 1070。
Noxol ETH 复合物数据表：1-纳瓦索尔和伯努利的复合物，水和乙醇溶液说明书
Product Data SheetNoxol ETHCopolymer of 1-naphtol and formaldehyde, solution in waterNoxol® ETH is a copolymer of 1-naphtol and formaldehyde, solution in water and ethanol. High-concentration antifouling agent particularly suited for manual application to difficult spots in reactors used for suspension polymerization of PVC.CAS number25359-91-5EINECS/ELINCS No.polymerTSCA statuslisted on inventorySpecificationsAppearance Slightly yellow transparent liquidEthanol9.0-13.0 %pH12.3–12.7Solids19.0-23.0 %CharacteristicsDensity, 20 °C 1.020 g/cm³Viscosity, 20 °C≤10 mPa.sStorageNouryon recommends to store Noxol® ETH in the temperature range from 0°C to 50°C.Freezing does not affect the performance of the product once thawed. Noxol® ETH should be stored under a nitrogen blanket. Prolonged exposure to oxygen may affect the quality of the product. Store in the original container with unbroken seal.Note When stored under the recommended storage conditions, Noxol® ETH willremain within the Nouryon specifications for a period of at least 9 months afterdelivery.Packaging and transportNoxol® ETH is available in 1.47 kg net PET bottles and 100 x 60 cc glass bottles. Both packaging and transport meet the international regulations. For the availability of other packed quantities contact your Nouryon representative. Noxol® ETH is classified as a non-dangerous good according to national and international transport regulations.Safety and handlingPlease refer to the Safety Data Sheet (SDS) for detailed information on the safe storage, use and handling of Noxol® ETH . This information should be thoroughly reviewed prior to acceptance of this product. The MSDS is available at/sds-search.CertificationsFood approvals - FDA: Formaldehyde-1-naphthol copolymer is authorized for use as an indirect food additive as specified in 21 CFR section 178.3860 (Release agents). Europe: Formaldehyde, copolymer with 1-naphthol is approved as an additive for the use in the manufacture of plastic materials and articles intended to come in contact with foodstuffs and listed as PM/Ref. No. 54930 in Annex III Section A to Directive 2002/72/EC. All minor components are also listed in Directive 2002/72/EC, as amended, respective have National approvals.All information concerning this product and/or suggestions for handling and use contained herein are offered in good faith and are believed to be reliable.Nouryon, however, makes no warranty as to accuracy and/or sufficiency of such information and/or suggestions, as to the product's merchantability or fitness for any particular purpose, or that any suggested use will not infringe any patent. Nouryon does not accept any liability whatsoever arising out of the use of or reliance on this information, or out of the use or the performance of the product. Nothing contained herein shall be construed as granting or extending any license under any patent. Customer must determine for himself, by preliminary tests or otherwise, the suitability of this product for his purposes.The information contained herein supersedes all previously issued information on the subject matter covered. The customer may forward, distribute, and/or photocopy this document only if unaltered and complete, including all of its headers and footers, and should refrain from any unauthorized use. Don’t copythis document to a website.Noxol® is a registered trademark of Nouryon Chemicals B.V. or affiliates in one or more territories.Contact UsPolymer Specialties Americas************************Polymer Specialties Europe, Middle East, India and Africa*************************Polymer Specialties Asia Pacific************************2022-9-14© 2022Polymer production Noxol ETH。
52-89-1,L-半胱氨酸,盐酸盐,技术规格说明书(SDS)
产品技术规格说明书由上海创赛科技有限公司收集整理，仅做参考使用。
L-半胱氨酸,盐酸盐详细介绍：
中文名称：
L-半胱氨酸,盐酸盐
中文别名：
L-半胱氨酸,盐酸盐;L-半胱氨酸盐酸盐水合物;L-丰胱胺酸盐酸盐;半胱氨酸,盐酸盐水合物;L-半胱氨酸盐酸盐(无水物);Α-氨基-Β-巯基丙酸盐酸盐;盐酸L-半胱氨酸;L-无水巯基丙氨酸盐酸盐;L-半胱氨酸盐酸盐无水物;DL-半胱氨酸盐酸盐;L-半胱氨酸盐酸盐,BR;L-半胱氨酸盐酸盐,无水;L―半胱氨酸盐酸盐无水物;L-半胱氨酸盐无水物;L-半胱胺酸盐酸盐;L-半胱胺酸盐酸盐无水物;L-巯基丙氨酸盐酸盐;L-盐酸半胱氨酸无水物;盐酸半胱氨酸;L-半胺氨酸盐酸盐;L-2-氨基-3-巯基丙酸盐酸盐;L-半胱氨酸盐酸盐-水物;L-无水半胱盐酸盐;半胱氨酸,盐酸盐;孚氨基酸;盐酸半胱氨酸(无水);L-半胱氨酸,盐酸盐,医药级,纯度:>99%
包装：
25, 100 g in poly bottle
生化/生理作用：
NMDA谷氨酸受体激动剂也是AMPA谷氨酸受体在高浓度时的激动剂。
查询关键词:“52-89-1，L-半胱氨酸,盐酸盐，L-Cysteine Hydrochloride，Sigma-Aldrich，上海现货”。
L-半胱氨酸,盐酸盐参考文献：
英文名称：
L-Cysteine hydrochloride
英文别名：
异丙醚 原辅料
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罗地亚产品目录
HLB：8/10.5/11.4/12.1/13.3/13.7
浊点：48-50/64-66/69-72/73-75/57-59/75-77
FentacareF08
无溶剂C9-C11烷基乙氧基化物
RhodafacRP－710
有机磷酸酯阴离子表面活性剂
微浊液体
245KG/桶
低泡,良好清洗、润湿、乳化性能;高电流忍受能力,可用于电解除油、化学除油除蜡和PCB除油整孔，也可以和低泡非离子复配，用于喷淋。
RhodocalTS-60/MX
磷酸酯类阴离子表面活性剂
粘稠液体
200KG/桶
含氨基的阴离子表面活性剂,低泡,高电流负荷稳定，常与油酸类的表活复配用于电解除油粉
产品名称
化学成分
外观
产品特点及应用
MirapolWT
阳离子聚合物
淡黄色液体
200KG/桶
无氰碱性镀锌的走位剂、整平剂，能明显缩短电镀时间，改善镀层的均匀性和深镀能力，节省锌的用量，同时提高镀层的耐腐蚀能力。
PH：7.5-8.5；添加量：1.5g/L；消耗量：40-70g/KAh
沉降剂：主用于磨削液中吸附金属屑沉降
黄色液体
200KG/桶
用于水基清洗配方表面活性剂混合物，低泡、耐酸碱，对于清除油脂类的有机油污非常有效，经常可以取代溶剂，降低成本，适用于高压和低压清洗设备。
Antarox L61/62/64
EO/PO嵌段共聚物
透明液体
204.12KG/桶
泡沫控制能力优异，适用范围广。可替代陶氏TergitolL、巴斯夫Pluronic PE、亨斯曼Surfonic POA-L系列。
欧洲药典7.5版
INDEX
To aid users the index includes a reference to the supplement in which the latest version of a text can be found. For example : Amikacin sulfate...............................................7.5-4579 means the monograph Amikacin sulfate can be found on page 4579 of Supplement 7.5. Note that where no reference to a supplement is made, the text can be found in the principal volume.
English index ........................................................................ 4707
Latin index ................................................................................. 4739
EUROPEAN PHARMACOPபைடு நூலகம்EIA 7.5
Index
Numerics 1. General notices ................................................................... 7.5-4453 2.1.1. Droppers...................
Amiloride hydrochloride_2016-88-8_DataSheet_MedChemExpress
Product Name:Amiloride hydrochloride CAS No.:2016-88-8Cat. No.:HY-B0285A Product Data SheetMWt:266.09Formula:C6H9Cl2N7O Purity :>98%Solubility:DMSO 50 mg/mL; Water 5 mg/mLy Mechanisms:Biological Activity:Amiloride hydrochloride is a potent epithelial sodium channel blockerPathways:Membrane Tranporter/Ion Channel; Target:Sodium Channel g ;g Amiloride hydrochloride is a potent epithelial sodium channel blocker.Target: Sodium Channel Amiloride is a pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reducessecretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the kidneys.This promotes the loss of sodium and water from the body,but References:[1]. Loffing, J. and B. Kaissling, Sodium and calcium transport pathways along the mammalian distalnephron: from rabbit to human. Am J Physiol Renal Physiol, 2003. 284(4): p. F628-43.[2]. Ji, H.L., et al., delta ENaC: a novel divergent amiloride-inhibitable sodium channel. Am J Physiol collecting ducts in the kidneys. This promotes the loss of sodium and water from the body, butwithout depleting potassium [1]. Amiloride, the first ENaC blocker to be applied to δβγ channels, has an I...Lung Cell Mol Physiol, 2012. 303(12): p. L1013-26.Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。
技术喷雾NO-CLEAN流化液洗劫产品列表和介绍说明书
Solvent CleanersNEW!Coming Soon!NO-CLEAN FLUX REMOVER3 Exciting New Products!t *1" "FSPTPM &MFDUSPOJDT $MFBOFS t ;FSP 70$ (FOFSBM $MFBOFSt )JHI 'MBTI .BJOUFOBODF $MFBOFS1611-12S 1626-G1626-GR1611-12S1626-11S 1626-11S S1610-12S1610-12S2IPA Electronics CleanerIntroducing E-LINE IPA – Isopropyl Alcohol (IPA) in new, convenient aerosol packaging. 99.8% pure anhydrous (minimal water) IPA is excellent for defl uxing, fi ber optics maintenance, stencil cleaning, tool cleaning, tape-head cleaning and other light-duty cleaning.• 99.8% pure IPA • Ideal for defl uxing, stencil cleaning & fi ber optics • Plastic safe • Low toxicity• Non-ozone depleting• Compliant with SCAQMD rule 1171Specifi cations for 99.8% IPA: Fed spec TT-1-735A (amend 3, notice 2) grades A&B, ASTM D770-051610-12S 12 oz. (433ml) aerosolAdditional Techspray IPA products:1610-100DSP 100 wipes in pop-up tub1610-50PK 50 individually wrapped wipes 1610-P 1 pint (0.47L) in plastic bottle 1610-PT 1 pint (0.47L) w/trigger sprayer 1610-G1 1 gallon (3.8L) in plastic bottle, 1/cs 1610-G4 1 gallon (3.8L) in plastic bottle, 4/cs 1610-5G 5 gallons (18.9L) in plastic container 1610-54G54 gallons (204L) in plastic drumPowerful & Economical CleanersNEW!NEW!1626-GHigh-FlashMaintenance CleanerE-LINE High-Flash is a non-chlorinated, light duty degreaser and electrical cleaner. Ideal for cleaning light oils and carbon residues from control panels, switch plates, enclosures, and work surfaces. Slower evaporation allows solvent to soak in and break down diffi cult soils.• Ideal for electrical & maintenance cleaning• High fl ash point • Non-chlorinated • Plastic safe • Low odor • Low toxicity• Non-ozone depleting 1626-11S 11 oz. (398ml) aerosol1626-G 1 gallon (3.8L) in metal container 1626-5G5 gallons (18.9L) in metal containerIntroducing Techspray’s E-LINE benchtop solvents. Formerly branded “Ecoline”, these cleaners are some of the most eff ective on the market, with great performance, low toxicity, and no ozone depletion. For companies accustomed to working with fl ammable materials, like fl uxes, alcohols and lubes, E-LINE off ers an economical alternative to chlorinated solvents.1626-11S1610-12SNEW!NEW!NEW!Zero-VOCGeneral Purpose CleanerE-LINE Zero-VOC is ideal for heavy-duty degreasing andfor removing paint and sticky adhesive residues. Becauseit is VOC-free, there are no regulatory concerns -- even insouthern California! Note: test fi rst on plastics and paintedsurfaces to check compatibility.• Pure Acetone• Ideal for removing inks & adhesives• VOC-free, Low GWP• Low toxicity• Non-ozone depleting1611-12S12 oz. (430ml) aerosol1611-P 1 pint (0.47L) in metal bottle1611-P1622-13S1622-10S1621-10S1620-10S1611-12SBrush Cleaning AttachmentE-LINE and G3 fl ux removers (1621-10SB &1631-16SB) are now available with a brushattachment. The spray heads are also adaptedto accept a commonly available brush system.Blue Shower Maintenance Cleaner• Heavy-duty industrial cleaning• Fast acting solvent1620-10S10 oz. (398ml) aerosolFlux Remover• Removes rosin and no-clean fl ux residues• Proven eff ective on lead-free1621-10S10 oz. (398ml) aerosol1621-10SB10 oz. (398ml) aerosol w/brushContact Cleaner• Ideal for contact cleaning & maintenance cleaning• Safe on plastic housings & enclosures1622-10S10 oz. (398ml) aerosol1622-13S13 oz. (517ml) aerosolFormerly “Ecoline” brand, these products have a new name but same power-ful performance. Hydrocarbon formulas are engineered to be fast-acting andeff ective, yet very economical. Eliminate brushing and scrubbing, saving timeand materials.• Plastic safe • Low toxicity• Residue free • Non-ozone depletingUniversal BulkCleaning Solvent• Powerful bulk cleaner• For cold cleaning and ultrasonic (unheated only)1621-G 1 gallon (3.8L) in metal container1621-5G 5 gallons (18.9L) in metal container1621-54G54 gallons (204L) in metal drum1621-5G1621-G1621-10SBh3SCAN FOR MOBILE SITEUS: 800-858-4043 | Int: 806-372-8523 |********************Non-Flammable Solvent CleanersUniversal Cleaning Solvent1651-16S 16 oz. (368ml) aerosol1651-G 1 gallon (3.8L) in glass container 1651-5G 5 gallons (18.9L) in metal container 1651-54G54 gallons (204L) in metal drumPlastic-Safe Cleaning Solvent1652-10S 10 oz. (208ml) aerosol1652-P 1 pint (0.47L) in glass bottle 1652-G1 gallon (3.8L) in glass containerMaintenance Cleaners1630-16S G3 Blue Shower, 16 oz. (368ml) aerosol 1635-20S G3 Industrial, 20 oz. (464ml) aerosol1632-16SG3 Contact Cleaner, 16 oz. (368ml) aerosolFlux Removers1631-16SG3 Flux Remover, 16 oz. (368ml) aerosol 1631-16SB G3 Flux Remover, 16 oz. (368ml) aerosol w/brush 1634-12SG3 No-Clean Flux Remover, 12 oz. (276ml) aerosolUniversal Bulk Cleaning Solvent1638-G 1 gallon (3.8L) in glass container 1638-5G 5 gallons (18.9L) in metal container 1638-54G54 gallons (204L) in metal drumTSSA-209Patented non-fl ammable cleaners are formulated to be powerful, yet economical. G3 does not contain nPB, TCE, Perc, and other highly toxic chemicals, providing both safety and performance.• Non-fl ammable • Residue free • Low toxicity• Rapid evaporation • Non-ozone depletingPrecision-V provides the performance and safety of G3, but with better plastic sensitivity and lower VOC. Precision-V Plastic-Safeformula is ideal for the most delicate plastics, like acrylics and polycarbonates.• Non-fl ammable• Safe on most plastics • Lower VOC • Residue free • Low toxicity• Rapid evaporation • Non-ozone depleting*aerosol aerosol。
海诺·泰勒水源头说明书
Halsey Taylor Owners Manual Non-Refrigerated FountainsIMPORTANTALL SERVICE TO BE PERFORMED BY AN AUTHORIZED SERVICE PERSONFIG. 1TUBE ISSECUREDIN POSITIONSIMPLY PUSH INTUBE TO ATTACHPUSH IN COLLETTO RELEASE TUBEPUSHING TUBE IN BEFOREPULLING IT OUT HELPS TORELEASE TUBEFIG. 2 OPERATION OF QUICK CONNECT FITTINGSOVL - E OVL - SIMPORTANT! INSTALLER PLEASE NOTE.THE GROUNDING OF ELECTRICAL EQUIPMENT SUCH AS TELEPHONE, COMPUTERS, ETC. TO WATER LINES IS A COMMON PROCEDURE. THIS GROUNDING MAY BE IN THE BUILDING OR MAY OCCUR AWAY FROM THE BUILDING. THIS GROUNDING CAN CAUSE ELECTRICAL FEEDBACK INTO A FOUNTAIN, CREATING AN ELECTROLYSIS WHICH CAUSES A METALLIC TASTE OR AN INCREASE IN THE METAL CONTENT OF THE WATER. THIS CONDITION IS AVOIDABLE BY USING THE PROPER MATERIALS AS INDICATED. ANY DRAIN FITTINGS PROVIDED BY THE INSTALLER SHOULD BE MADE OF PLASTIC TO ELECTRICALLY ISOLATE THE FOUNTAIN FROM THE BUILDING PLUMBING SYSTEM.NOTE: WATER FLOW DIRECTION BUILDING WATER INLET SERVICE STOP(NOT FURNISHED)1/4" O.D. TUBE WATER INLET TO COOLER 3/8" O.D. UNPLATED COPPER TUBE CONNECT COLD WATER SUPPLYFIG. 3OVL - SOVL - ELEGEND:A = 1-1/4" O.D. Waste Tube (Trap & Elbow Not Provided)B = 3/8" O.D. Unplated Copper Tube Connect (Water Inlet)Fig. 4INSTALLATION INSTRUCTIONS1. This fountain is to be mounted on a smooth, flat, finished wall surface, with adequate support structure.2. Establish rim height fountain is to be mounted.3. Refer to rough-in for plumbing.4. Locate and install trap. (Trap not furnished.)5. Install shut-off valve on building water supply. (Shut-off valve not furnished.)6. Remove access panel from bottom of fountain.7. Locate and install fountain using 3/8" (10 mm) (minimum) lag screws or bolts (not furnished).CAUTION: This fountain is rated for inlet water pressure of 20-90 PSI. Should the inlet water supply exceed 90 PSI, a pressure reducing regulator should be used.8. Connect fountain to building supply line with a shut-off valve and install a 3/8" (10 mm) unplated copper water line between the valve and fountain. Remove any burrs from outside of water line. Insert water line to a positive stop, approximately 3/4" (19 mm) on inlet side of strainer. DO NOT SOLDER TUBES INSERTED INTO THE STRAINER AS DAMAGE TO THE O-RINGS MAY RESULT .9. To remove waste elbow, remove (4) screws (item 18) and drop bottom plate (item 20) and push bar (item 2) down. Waste elbow slip nut (item 13) is now accessible. Connect fountain drain.10. Turn “ON” water supply and check all connections for leaks.11. Adjust projector stream height.12. If needed, adjust push arm/regulator clearance by turning phillips head screw (item 26) on regulator bracket assy. (item 30). Turning screw CCW should correct water coming out of projector continuously.13. Reinstall access panel using screws provided.TROUBLE SHOOTING AND MAINTENANCEOrifice Assy: Mineral deposits on orifice can cause water flow to spurt or not regulate. Mineral deposits may be removed from the orifice with a small round file or small diameter wire. CAUTION: DO NOT file or cut orifice material.Stream Regulator: If orifice is clean, regulate flow as in instructions above. If replacement is necessary, see parts list for correct regulator part number.Actuation of Quick Connect Water Fittings: Fountain is provided with lead-free connectors which utilize an o-ring water seal. To remove tubing from the fitting, relieve water pressure, push in on the gray collar while pulling on the tubing.(see Fig.2) To insert tubing, push tube straight into fitting until it reaches a positive stop, approximately 3/4".CAUTION: To preserve the quality and keep this AZTEC GOLD finish clean and spot free, clean this surface with only mild detergent or window cleaner and polish with a soft cloth. DO NOT use any abrasive cleaners or harsh chemicals. They WILL damage the finish!Fig. 523241514RegulatorMounting BracketCARE AND MAINTENANCE OF HALSEY TAYLOR MARBLYTE FOUNTAINSMarblyte provides an extremely durable , non-porous surface which resists staining. Care is very simple. Routine cleaning with a soft sponge or cloth, or with water or non-abrasive aerosol foam cleaner, is all that is normally needed to give many years of trouble free service. Cleaners left standing on the fountain surface can dull the surface finish. Be certain to rinse all cleaning agents completely and polish with a soft cloth. Harsh abrasivecleaners are not required and should not be used. Mild abrasives such as liquid automotive cleaning compound or baking soda paste will remove simple scratches and stains. Cigarette burns can normally be removed without noticeable effect. Deeper scratches or gouges can be corrected with fine grit sandpaper (240 grit then 400 grit) or a green scotchbrite pad. To maintain or regain luster and make cleaning easier, periodic applications of automobile wax or like products will keep the finish looking like new.DESCRIPTION26990C 26988C 55836C 55991C 51546C 45396C 51544C 10032274056016027050864045400C 10157054056051575C 11034620855010163745155016163730864045398C 45683C 45682C 10002334056016157080855061314C 50986C 27006C 27342C 55951C 55952C 55953C 27000C 27344C 70861C 55840C 55839C 27002C 27338C 27004C 27340C 28328C 15005C 40045C 27008C 70856C 70854C 50198C 51667C 28327C 28326C 55996C 70793C 56159C 56092C12345678910111213141516171819202122232425262728293031NS NS NS NSP ART NO.Bottom Cover (OVL-S)Bottom Cover (OVL-E)Push Arm ActuatorPush Arm Actuator - AG BubblerBubbler - AG Bubbler- MARBL Bubbler Gasket Strainer PlateStrainer Plate - AG Drain Gasket Packing Ring Drain Nut Friction Ring Drain PlugDrain Plug/Strainer - AG Waste Elbow (OVL-E)Waste Elbow (OVL-S)Waste Tube Gasket Slip Nut RegulatorRegulator Holder BasinBasin - AGBasin - GRAY MRBL Basin - BLACK MRBLBasin - GOLDEN SAND MRBL Basin LinerBasin Liner - AG Screw # 10-24 x 2T op Plate - Actuator Bottom Plate - Actuator Arm w/Weldnuts (OVL-E)Carrier Arm - AG (OVL-E)Arm w/Weldnuts (OVL-S)Carrier Arm - AG (OVL-S)Regulator Mounting Bracket Nut - Retaining Nut Hex - UNPLTD Reaction BracketScrew #10-24 x .38 PHMS Rod - Pivot Bushing SnapBumper - Reg. Valve Assy Arm - Reg. Activating Arm - Reg. Adjustment Strainer Elbow-1/4"Bubbler Nipple AssyTubing - Poly (Cut to Length)ITEM NO.PARTS LISTFOR PARTS CONTACT YOUR LOCAL DISTRIBUTOR OR VISIT OUR WEBSITE WWW.HALSEYTA 2222 CAMDEN COURT OAK BROOK, IL 60523630.574.3500PRINTED IN U.S.A.FIG. 6FIG. 719220292629262730223125Stream Height Adjustment18510891213678111See Fig. 721See Fig. 53, 41617See Fig. 6。
利特莫韦液体制剂化学品安全技术说明书
版本1.19修订日期:2023/04/04SDS编号:66855-00020前次修订日期: 2022/10/01最初编制日期: 2015/02/271. 化学品及企业标识产品名称: Letermovir Liquid Formulation制造商或供应商信息制造商或供应商名称: MSD地址: 199 Wenhai North RoadHEDA, Hangzhou - Zhejiang Province - CHINA310018电话号码: 908-740-4000应急咨询电话: 86-571-87268110电子邮件地址: **********************推荐用途和限制用途推荐用途: 制药的限制用途:不适用2. 危险性概述紧急情况概述外观与性状: 液体颜色: 澄清气味: 无臭非危险物质或混合物。
GHS危险性类别非危险物质或混合物。
GHS标签要素无需危险象形图、信号词、危险性说明及防范说明。
物理和化学危险根据现有信息无需进行分类。
健康危害根据现有信息无需进行分类。
环境危害根据现有信息无需进行分类。
版本1.19修订日期:2023/04/04SDS编号:66855-00020前次修订日期: 2022/10/01最初编制日期: 2015/02/27GHS未包括的其他危害未见报道。
3. 成分/组成信息物质/混合物: 混合物组分化学品名称化学文摘登记号(CAS No.)浓度或浓度范围 (% w/w) Letermovir917389-32-3>=1 - <2.54. 急救措施一般的建议: 出事故或感觉不适时，立即就医。
在症状持续或有担心,就医。
吸入: 如吸入，移至新鲜空气处。
就医。
皮肤接触: 如接触，立即用肥皂和大量水冲洗皮肤。
脱去被污染的衣服和鞋。
就医。
重新使用前要清洗衣服。
重新使用前彻底清洗鞋。
眼睛接触: 谨慎起见用水冲洗眼睛。
如果刺激发生并持续，就医。
食入: 如吞咽：不要引吐。
盐酸林可霉素注射液
盐酸林可霉素注射液盐酸林可霉素注射液拼音名：Yansuan Linkemeisu Zhusheye英文名：Lincomycin Hydrochloride Injection书页号：2000年版二部－631本品为盐酸林可霉素的灭菌水溶液。
含林可霉素(C18H34N2O6S) 应为标示量的90.0％～110.0％。
【性状】本品为无色的澄明液体。
【鉴别】取本品与林可霉素对照品，分别加流动相制成每1ml 中含2mg 的溶液，照含量测定项下的高效液相色谱条件试验，供试品主峰的保留时间应与对照品主峰的保留时间一致。
【检查】酸度取本品，加水制成每1ml 中含0.1g的溶液，依法测定（附录ⅥH），pH值应为3.0 ～5.5 。
颜色本品应无色，如显色，与黄色或黄绿色2号标准比色液（附录ⅨA第一法）比较，不得更深。
无菌取本品，分别加入100ml 0.9％无菌氯化钠溶液中使溶解，用薄膜过滤法处理后，依法检查（附录ⅪH），应符合规定。
异常毒性与细菌内毒素照盐酸林可霉素项下的方法检查，应符合规定。
林可霉素Ｂ取本适量，照盐酸林可霉素项下的方法检查，林可霉素Ｂ的峰面积不得过林可霉素与林可霉素Ｂ峰面积之和的5.0 ％。
其他应符合注射剂项下有关的各项规定（附录ⅠB）。
【含量测定】照高效液相色谱法（附录ⅤD）测定。
色谱条件与系统适用性试验用十八烷基硅烷键合硅胶为填充剂；0.05mol/L 硼砂溶液，（用85％磷酸溶液调节pH值至5.0 ）－甲醇－乙腈(60:36:4) 为流动相；检测波长为214nm 。
理论板数按林可霉素峰计算应不低于1500。
测定法精密量取本品适量，用流动相稀释成每1ml中含林可霉素2mg的溶液，摇匀，取10μl 注入液相色谱仪，照盐酸林可霉素项下的方法测定。
【类别】同盐酸林可霉素。
【规格】按C18H34N2O6S计算(1) 2ml:0.6g (2) 10ml:3g【贮藏】密闭保存。
【药理毒理】本品对常见的需氧革兰阳性菌有较高抗菌活性，如金黄色葡萄球菌（包括耐青霉素G者）、表皮葡萄球菌、β溶血性链球菌、草绿色链球菌和肺炎链球菌等。
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Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
Leonurine (hydrochloride), a major alkaloid compound extracted from Leonurus japonicas Houtt. (Labiatae), is considered to have
antitumor roles.In Vitro: Leonurine hydrochloride significantly inhibits the proliferation of H292 cells in a time– and dose–dependent manner, and induces G0/G1 cell–cycle arrest. Coincidentally, Leonurine hydrochloride treatment at a dose of 10, 25, and 50 μM for 24 h increases apoptotic ratio from 4.9±0.43% to 11.5±1.12%, 19.3±1.16%, and 61.3±6.69%, respectively. The inhibition effect of Leonurine hydrochloride on H292 cells is associated with the loss of MMP and the generation of ROS. The phosphorylation level of p38 is increased and Akt phosphorylation is reduced by Leonurine hydrochloride treatment. Furthermore, Leonurine hydrochloride treatment increases the expression levels of caspase–3, caspase–9 and Bax/Bcl–2[1]. In RAW 264.7 cells and mouse bone marrow
monocytes (BMMs), Leonurine hydrochloride suppresses RANKL–induced osteoclastogenesis and actin ring formation in a dose–dependent manner. Leonurine hydrochloride targets RANKL–induced osteoclastogenesis and bone resorption at an early stage. Molecular analysis demonstrates that Leonurine hydrochloride attenuates RANKL–induced NF–κB signaling by inhibiting the phosphorylation and degradation of IκBα and NF–κB p65 nuclear translocation. Leonurine hydrochloride inhibits the RANK–TRAF6association triggered by RANKL binding and the phosphatidylinositol 3–kinase (PI3K)/Akt axis, without significantly affecting the extracellular signal–regulated kinase (ERK)/mitogen–activated protein kinase (MAPK) and AP–1 signaling pathways. Leonurine hydrochloride attenuates the RANKL–stimulated expression of osteoclast–related genes including NFATc1, tartrate resistant acid phosphatase (TRAP), cathepsin K, and osteoclast–associated receptor (OSCAR)[2]. Leonurine hydrochloride significantly increases the [Ca 2+]i, PLC activity, and relative production of PKC protein in myometrial cells [3].In Vivo: In in vivo experiments, leonurine hydrochloride treatment elevates the ET level and ET/NO ratio in rats with induced
abortions and up–regulated ETA mRNA expression, but there is no change in ETB mRNA [3]. In in vivo experiments, compared with the model group, Leonurine hydrochloride treatment markedly reduces the volume of bleeding and intrauterine residual, and significantly shortens the duration of bleeding. From the contraction curve, Leonurine hydrochloride notably reinforces the
frequency and tension of uterine contractions. Leonurine hydrochloride remarkably elevates the serum estradiol level in rats, but has no obvious effect on progesterone level [4].
References:
[1]. Mao F, et al. Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria–dependent pathway. Pharm Biol. 2015;53(11):1684–90.
[2]. Yuan FL, et al. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF–κB and PI3K/Akt signaling pathways. Bone. 2015 Jun;75:128–37.
[3]. Li X, et al. Effect of leonurine hydrochloride on endothelin and the endothelin receptor–mediated signal pathway in medically–induced incomplete abortion in rats. Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):299–303.
Product Name:
Leonurine (hydrochloride)Cat. No.:
HY-N0741A CAS No.:
24735-18-0Molecular Formula:
C 14H 22ClN 3O 5Molecular Weight:
347.79Target:
Toll–like Receptor (TLR); Autophagy Pathway:
Immunology/Inflammation; Autophagy Solubility:
DMSO: ≥ 31 mg/mL
[4]. Li X, et al. Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats. Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):375–80.
Caution: Product has not been fully validated for medical applications. For research use only.
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