Canertinib_dihydrochloride_LCMS_04044_MedChemExpress

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MK2-IN-1_hydrochloride_SDS_MedChemExpress

Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Jul.-24-2017Print Date:Jul.-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :MK2-IN-1 (hydrochloride)Catalog No. :HY-12834ACAS No. :1314118-94-91.2 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:MK2 InhibitorFormula:C27H26Cl2N4O2Molecular Weight:509.43CAS No. :1314118-94-94. 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 Pink to red (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。

地拉韦定甲磺酸盐的波谱学数据与结构表征

明
和
的存在；1229 cm - 1 的强峰为
上的 CH2 非平面摇摆振动，而 753 cm - 1 的
CH2 平面摇摆振动又进一步说明有连续两个 - CH2 CH2 - 的存在，可以验证分子中
的存在。
甲磺酸地拉韦定与地拉韦定的 IR 谱图比较，地拉韦定与甲磺酸成盐后，其中一个 NH 转化为
关键词甲磺酸地拉韦定，二维核磁共振谱，质谱，红外
1引言
地拉韦定甲磺酸盐（ delavirdine mesylate，Rescriptor）是美国 FDA 于 1997 年批准上市的非核苷类逆转录酶抑制剂［1］，与其它抗逆转录病毒药物联合应用，即“ 鸡尾酒疗法”治疗艾滋病的第三种或第四种药物，已批准的适应症为应用于治疗由 I 型人免疫缺陷病毒（ HIV-1）引起的感染。地拉韦定甲磺酸盐化学名为 1［- 3［- （1-甲基乙基）氨基］-2-吡啶］-4［- 5（- 甲磺酰基）-1-氢-2-吲哚］羰基-哌嗪甲基磺酸盐，为白色或类白色结晶粉末［2］，熔点 220 ～ 222℃ 。
一维13C NMR 谱观察到 20 条谱线，对应于 23 个碳原子。DEPT 谱观察到 16 个质子碳，其中 %CH3 甲基碳 4 个，%CH2 % 次甲基碳 4 个，叔碳原子 8 个。13C NMR 吸收峰 δ 126. 77、δ 130. 27、 δ 130. 53、δ 133. 58、δ 137. 62、δ 145. 85 和 δ 161. 89 在 DEPT 谱上消失，说明它们是季碳原子，并分别对应于 21、23、18、20、12、7、13 碳原子。碳原子个数和类型与地拉韦定甲磺酸盐化学结构式一致。

酒石酸卡巴拉汀的产品说明书

SMILES：O=C(OC1=CC=CC([C@@H](N(C)C)C)=C1)N(CC)C.O=C(O)[C@H](O)[C@@H](O)C(O)=O
参考文献：
[1]. Kurz A, Farlow M, Lefèvre G. Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease: a review. Int J Clin Pract. 2009 May;63(5):799-805.
中文别名：
酒石酸卡巴拉汀;(S)-N-乙基-N-甲基氨基甲酸-3-[(1-二甲氨基)乙基]苯酯酒石酸盐;卡巴拉汀或利斯的明酒石酸盐;L-酒石酸卡巴拉汀;2,3',4-三溴二苯醚;N-乙基甲基氨基甲酰氯;Rivastigmine L-Tartrate L-酒石酸卡巴拉汀;酒石酸卡巴拉汀 USP标准品;酒石酸卡巴拉汀Rivastigmine tartrate;酒石酸卡巴拉汀标准品;酒石酸卡巴拉汀氢 EP标准品;酒石酸利凡斯的明;卡巴拉丁;卡巴拉汀酒石酸盐;重酒石酸卡巴拉汀;重酒石酸利凡斯的明;(S)-N-乙基-N-甲基氨基甲酸-3-[(S)-1-(二甲氨基)乙基]苯酯酒石酸盐;氘代重酒石酸利斯的明-d6;酒石酸卡巴拉汀中文别名：卡巴拉汀或利斯的明酒石酸盐;酒石酸利伐斯的明;酒石酸利瓦斯汀;利斯的明酒石酸盐;卡巴拉汀重酒石酸盐
熔点
123-1250C
分子式
C18H28N2O8
分子量
400.423
闪点
145ºC
精确量
400.18457
PSA
147.84
LogP
0.6371

非索非那定片29页

2020/3/29
上市信息
非索非那定fexofenadine，为一抗过敏药物，于2019年上市后，相继在美国\澳大利亚、澳地利、比利时、巴西、加拿大、丹麦、芬兰、法国、德国、希腊、香港、印度、日本、卢森堡、马来西亚、墨西哥、荷兰、新西兰、挪威、葡萄牙、南非、西班牙、瑞典、瑞士、泰国、英国等数十个国家和地区上市，用于治疗过敏性鼻炎、荨麻疹等过敏性疾病。
盐酸非索非那定片
----毕馨
【分子式】 C32H39NO4·HCl 【分子量】 538.13 【性状】本品为薄膜衣片，除去包衣后显白色或类白色。
2020/3/29
上市信息
赫斯特公司开发，2019年首次在欧洲上市 2019年FDA批准了SANOFI AVENTIS的新药申请 2019年10月FDA批准口服混悬剂
2020/3/29
适应症
季节性过敏性鼻炎适用于缓解成人和6岁及6岁以上的儿童的季节性过敏性鼻炎相关的症状。如打喷嚏，流鼻涕，鼻、上腭、咽喉发痒，眼睛发痒、潮湿、发红。
慢性特发性荨麻疹适用于治疗成人和6岁及6岁以上儿童的慢性特发性荨麻疹的皮肤症状，能够减轻瘙痒和风团的数量。
2020/3/29
2020/3/29
毒性反应
急性毒性试验：口服毒性低，小鼠和大鼠口服LD50均大于 5000mg/kg
亚急性毒性试验：犬连续口服本品 100mg/kg28天，均未观察到任何不良反应发生
2020/3/29
毒性反应
体内和体外试验结果表明，非索非那定没有致癌性、致突变性
支物生殖毒性研究：当给予大鼠和家兔口服特非那丁高达300mg/kg，它们产生的非索非那定血浆AUC值分别相当于人体治疗值（60mg，一日二次）的4倍和37倍，结果均未发现有致畸的作用。

人参皂苷治疗骨性关节炎的研究进展

特产研究163Special Wild Economic Animal and Plant ResearchDOI：10.16720/ki.tcyj.2023.093人参皂苷治疗骨性关节炎的研究进展郭校妍1，张伟东1，张扬1※（吉林大学药学院，吉林长春130021）摘要：人参在防治关节软骨损伤退变及参与体外培养软骨细胞修复关节软骨缺损中具有较好治疗前景。

人参皂苷作为人参的主要药理活性成分，在治疗骨性关节炎的进程中发挥关键作用。

人参皂苷根据不同的结构被分为不同的类型，各类型均含有多种人参皂苷单体成分，其治疗骨性关节炎的机制也各不相同。

本文对不同人参皂苷单体治疗骨性关节炎的研究进行梳理和总结，探讨其治疗骨性关节炎的潜在可能性和作用机制，为后期临床应用提供依据。

关键词：骨性关节炎；人参皂苷；信号通路中图分类号：R285文献标识码：A文章编号：1001-4721（2023）03-0163-06Research Progress of Ginsenosides in the Treatment of OsteoarthritisGUO Xiaoyan1,ZHANG Weidong1,ZHANG Yang1※（School of Pharmaceutical Sciences,Jilin University,Changchun130021,China）Abstract:Ginseng has pharmacological effects such as anti-inflammatory,antioxidant,antidepressant,anti-Alzheimer's and anti-athero-sclerosis.Current studies have found that it has good therapeutic prospects in preventing degeneration of articular cartilage damage and parti-cipating in in vitro culture of chondrocytes to repair articular cartilage defects.Ginsenosides,as the main pharmacological active component of ginseng,also play an important role in the process of treating osteoarthritis.Ginsenosides can be classified into different types because of their different structures,and each type contains a variety of ginsenoside monomer components with different mechanisms for the treatment of osteoarthritis.In this paper,we review the research progress of different ginsenoside monomers in the treatment of osteoarthritis,and ex-plore their potential possibilities and mechanisms for the treatment of osteoarthritis,so as to provide a basis for later clinical application. Key words:osteoarthritis;ginsenosides;signaling pathway骨性关节炎（Osteoarthritis,OA）是一种退行性病变，系由于增龄、肥胖、遗传、劳损、创伤、关节先天性异常和关节畸形等诸多因素引起的关节软骨退化损伤、关节边缘和软骨下骨反应性增生。

恩曲替尼化学式-概述说明以及解释

恩曲替尼化学式-概述说明以及解释1.引言1.1 概述概述恩曲替尼（英文名称：Entrectinib）是一种靶向抗癌药物，属于酪氨酸激酶抑制剂。

它通过抑制肿瘤细胞中的激酶信号通路，发挥抗肿瘤的作用。

恩曲替尼被广泛应用于非小细胞肺癌、神经母细胞瘤和其他肿瘤的治疗。

该药物的化学性质使其具备出色的抗肿瘤效果。

恩曲替尼的分子式为C31H34Cl2N5O3，分子量为602.54克/摩尔。

其分子结构复杂，由多个不同原子组成的编织网状结构构成。

这种特殊的结构赋予了恩曲替尼优异的特性，包括其强大的抑制肿瘤生长能力和独特的靶向治疗机制。

除了化学性质外，恩曲替尼还具有一系列独特的物理性质。

该药物为白色或类白色结晶粉末，具有极高的纯度要求。

其熔点为210-215，在这个温度范围内可以保持稳定。

此外，恩曲替尼在常温下可溶于一些有机溶剂，如二氯甲烷和二甲基亚砜，但不溶于水。

在药理作用方面，恩曲替尼主要表现出针对肿瘤细胞的抗增殖和抗转移能力。

它通过干扰肿瘤细胞的激酶信号通路，阻止肿瘤细胞的分裂和生长。

此外，恩曲替尼还具有特异性靶向治疗作用，能够选择性地抑制特定的激酶，从而实现精确的治疗效果。

然而，恩曲替尼也存在一些副作用，如恶心、呕吐、疲劳和食欲不振等，这些副作用需在使用时留意并及时处理。

综上所述，恩曲替尼作为一种靶向抗肿瘤药物，具有复杂的化学性质、独特的物理性质以及较广泛的药理作用。

进一步的研究和应用将有助于更好地发掘恩曲替尼的潜力，为肿瘤治疗提供新的突破和可能性。

1.2 文章结构文章结构部分的内容如下：文章结构部分主要介绍了整篇文章的组织结构和内容安排。

本文的目录分为引言、正文和结论三个部分。

引言部分主要是对整篇文章的背景和目的进行概述，并对恩曲替尼的化学式进行引入。

接着，文章结构部分将详细介绍恩曲替尼的化学性质、物理性质和药理作用。

最后，结论部分将对恩曲替尼的化学性质、物理性质和药理作用进行总结。

在正文部分，恩曲替尼的化学性质将包括分子式、分子量和结构式的介绍。

高效液相色谱法测定延胡索药材中7种异喹啉类生物碱的含量

高效液相色谱法测定延胡索药材中7种异喹啉类生物碱的含量赵新娟;沈梅;石俊敏;韩伟立【摘要】本文建立了同时测定延胡索中巴马汀、小檗碱、去氢紫堇碱、四氢巴马汀、异紫堇球碱、紫堇碱和四氢黄连碱7种主要异喹啉生物碱含量的高效液相色谱方法,并考察了不同来源延胡索中异喹啉生物碱的含量.采用Agilent SB C18柱色谱柱(4.6×250 mm,5μm),流动相为乙腈-0.1％的醋酸水溶液(三乙胺调pH至5.0),梯度洗脱,流速为1.0 mL/min,检测波长为280nm.巴马汀、小檗碱、去氢紫堇碱、四氢巴马汀、异紫堇球碱、紫堇碱和四氢黄连碱在2.0～40.1、2.0～39.5、5.1～101.3、5.0～99.8、2.1 ～41.2、5.0～100.1 μg/mL和2.0 ～39.7μg/mL浓度范围内线性良好,平均加样回收率分别为95.6％、96.1％、96.5％、101.4％、101.9％、97.3％和102.3％,RSD分别为2.77％、2.50％、3.33％、4.18％、2.93％、2.86％和2.60％.不同来源延胡索样品中7种异喹啉类生物碱含量差异较大,研究表明该方法准确、可靠,可用于延胡索原药材质量控制.【期刊名称】《天然产物研究与开发》【年(卷),期】2015(027)012【总页数】5页(P2074-2078)【关键词】高效液相色谱法;异喹啉类生物碱;延胡索;含量测定【作者】赵新娟;沈梅;石俊敏;韩伟立【作者单位】山西省晋中市第一人民医院药剂科,晋中030600;南方医科大学公共卫生与热带医学学院卫生检测中心,广州510515;华南师范大学药物研究院,广州510632;南方医科大学公共卫生与热带医学学院卫生检测中心,广州510515【正文语种】中文【中图分类】R917延胡索为罂粟科紫堇属植物延胡索(Corydalis yanhusuo W.T.Wang)的干燥块茎，其具有活血、利气和止痛的功效。

化学名称缩写

AO抗氧剂或防老剂
APAO非晶性α-烯烃
APHA美国公共卫生事业协会
APR芳烃石油树脂
APS氨基丙基三乙氧基硅烷、过硫酸铵
A-PVA无规聚乙烯醇
AR丙烯酸酯橡胶、分析纯
AS澳大利亚标准
ASC胶黏剂与密封剂委员会
ASTM美国材料试验学会
ATBN端氨基液体丁腈橡胶
ATH氢氧化铝（三水合氧化铝）
ATO三氧化二锑
PIB聚异丁烯
PM丙二醇甲醚
PMA聚马来酸酐、丙二醇甲醚醋酸酯PMAA聚甲基丙烯酸
PMDA均苯四甲酸二酐
PMMA聚甲基丙烯酸甲酯
PMP丙二醇甲醚丙酸酯
PMS聚α-甲基苯乙烯
PN波兰国家标准
PNA苯基-β-萘胺
PNBR粉末丁腈橡胶
POE聚氧化乙烯
POP对辛基苯酚
PPA多聚磷酸
PPD六氢吡啶、对苯二胺
PPESK聚芳醚砜酮
EAL乙醇
EB水性环氧丙烯酸酯
EC乙基纤维素
ECH环氧氯丙烷
EDA乙二胺
EDTA乙二胺四乙酸
EEP 3-乙氧基丙酸乙酯
EEW环氧当量
EG乙二醇
EGDA二丙烯酸乙二醇酯
EGDE乙二醇二缩水甘油醚（669稀释剂）EGDMA双甲基丙烯酸乙二醇酯
2-EI 2-乙基咪唑
Em乳化剂
EMA甲基丙烯酸乙酯
EMI-2，4 2-乙基-4-甲基咪唑
BHT 2，6-二叔丁基对甲酚（264）
BIIR溴化丁基橡胶
Bis A双酚A
Bis F双酚F
Bis S双酚S
γ-BL γ-丁内酯
BMA甲基丙烯酸丁酯
BMI双马来酰来胺
BN安息香
BOA已二酸苄基辛基酯

LCMS检测西他沙星原料中基因毒性杂质的含量

LC-MS检测西他沙星原料中基因毒性杂质的含量石莹1宋雪洁3李浩冬2路显锋2*1药物研究院分析所，扬子江药业集团，泰州2253212药物制剂新技术国家重点实验室，扬子江药业集团，泰州2253213质量管理部，扬子江药业集团，泰州225321摘要建立了LC-MS 法测定西他沙星中基因毒性杂质对甲苯磺酸甲酯和对甲苯磺酸乙酯含量的方法。

方法:采用Agilent Poroshell 120 EC-C18色谱柱；流动相为纯水（0.1%甲酸）:甲醇（V/V）=60:40；稀释剂为乙腈（0.1%甲酸）:纯水（V/V）=50:10；柱温为40℃；进样体积为5µl；流速为0.4ml/min；采用正离子模式进行扫描。

对甲苯磺酸甲酯测定浓度在0.76ng/ml~15.27ng/ml范围内，线性关系良好；对甲苯磺酸乙酯测定浓度在0.75ng/ml~15.01ng/ml范围内，线性关系良好。

对甲苯磺酸甲酯的定量限为0.0038ng；对甲苯磺酸乙酯的定量限为0.0038ng。

杂质回收率在限度浓度80%、100%和160%三个浓度水平均在90~110%之间，该方法准确度良好。

该方法适用于西他沙星原料中对甲苯磺酸甲酯和对甲苯磺酸乙酯的检测。

西他沙星(sitafloxacin)是日本第一制药有限公司继左氧氟沙星后开发出的一种强力广谱新氟喹诺酮类抗菌剂，该药对革兰氏阳性球菌，革兰氏阴性菌以及厌氧菌的抗菌活性是左氧氟沙星的4～32倍，同时对肺炎球菌DNA 促旋酶和拓扑同功酶有双重抑制作用。

临床表现有极广的抗菌谱，特别是对呼吸道的病菌有极强的抗菌活性。

因西他沙星的一个起始物料为对甲苯磺酸盐，在后续反应中对甲苯磺酸若有残留，可能会与溶剂甲醇、乙醇反应生成具有基因毒性的杂质—对甲苯磺酸甲酯和对甲苯磺酸乙酯，故采用LC-MS法对产品中的对甲苯磺酸甲酯/乙酯进行控制。

1、实验部分1.1仪器与试药Agilent 1200液相色谱仪(美国安捷伦公司)；Agilent 6460三重串联四极杆质谱仪(美国安捷伦公司)；XP205型电子天平(瑞士梅特勒托利多公司)。

锂离子电池电解液添加剂物性数据

1,4-丁基磺酸内酯，
1,3-丙烷磺酸内酯 (1,3-PS)
1,3-Propane sultone；
精品资料
______________________________________________________________________________________________________________
______________________________________________________________________________________________________________
化学名称
别名英文名称 CAS 号
分子式
锂离子电池电解液添加剂物性数据
环己基苯(CHB)
CAS 号分子式
4427-96-7 C5H6O3
分子结构
分子量熔点/沸点/闪点
114.10
？/237℃/733mmHg/96.6
密度（g/mL at 25℃）粘度（40℃）折光率外观特性
1.188
1.45 无色液体
见附注
1073-05-8 C3H6O4S
1-Phenyl-2-acetone
2、添加了 MMDS 的电池具有很好的高温循环性能。适用于动力电池，特别是锰酸锂做正极材料的动力电池，MMDS 能防止高温下熔出的 Mn 吸附在负极表面，抑制了阻抗上升，有效提高了循环周期特性，可以大大增加其循环寿命。
变色。还可用作底涂剂。
包装材料为 PE
精品资料
______________________________________________________________________________________________________________

三氟乙酸脱苄基O-debenzylation_of_ortho-substituted_phenols_with_trifluoroacetic_acid

Mild,efﬁcient and rapid O-debenzylation of ortho -substituted phenols with triﬂuoroacetic acidSteven Fletcher *,Patrick T.Gunning *Department of Chemistry,University of Toronto,Mississauga,ON L5L 1C6,Canadaa r t i c l e i n f o Article history:Received 21May 2008Revised 2June 2008Accepted 4June 2008Available online 10June 2008a b s t r a c tThe mild and efﬁcient deblocking of aryl benzyl ethers with TFA is reported.Cleavage was fastest with ortho -electron-withdrawing groups on the phenolic ring,which we have attributed to a proton chelation effect,furnishing the deprotected phenols in excellent yields.The corresponding para -methoxybenzyl,allyl and iso -propyl ethers were also cleanly removed under these conditions.In addition,the selective aryl benzyl ether debenzylation in the presence of benzyl ester,Cbz carbamate and Boc carbamate func-tionalities was also observed.Crown Copyright Ó2008Published by Elsevier Ltd.All rights reserved.Phosphotyrosines feature in the design of inhibitors of several protein targets,including protein tyrosine phosphatase 1B (PTP1B).1However,these moieties suffer from hydrolytic lability to cellular phosphatases and poor cell penetration due to the asso-ciated dianionic charge.1To address these issues,salicylic acid derivatives (and closely-related analogues)have become popular mimetics of phosphotyrosine in small molecule inhibitors.1–5Turk-son et al.have recently reported on NSC74859(1),a potent,sali-cylic acid-based inhibitor of the oncogenic protein Stat3.6As part of our structure–activity relationship (SAR)studies on NSC74859(1),we sought to debenzylate both the phenol ether and benzoate ester in 2without reducing the aryl-bromide bond,a common undesired side reaction that occurs with hydrogen gas and Pd/C catalyst.7O -Benzyl-protected phenols are known to undergo debenzyla-tion with triﬂuoroacetic acid (TFA)8by an initial protonation of the weakly basic phenol oxygen,although additives such as strongorganic acids (e.g.,triﬂuoromethanesulfonic acid 9)or a large excess of nucleophilic scavenger (e.g.,thioanisole,which accelerates the reaction by a ‘push–pull’mechanism 10)are typically required.Re-cent work by Ploypradith et al.describes the mild deprotection of aromatic ethers with sub-stoichiometric para -toluenesulfonic acid on solid support.11In a special case,O -benzyl-protected ortho -nitrophenol was cleaved rapidly (<5min)with neat TFA,12which we considered was due to the ability of the substrate to chelate a proton since the structurally-similar ortho -hydroxybenzoates (salicylates)are well-known to chelate copper ions and iron ions.We reasoned that 2(and indeed 3)may similarly undergo acceler-ated debenzylation with TFA.In fact,as shown in Scheme 1,treat-ment of 2(or 3)with a 1:1mixture of TFA/toluene led to rapid debenzylation (5min for 2;1h for 3)in 91%yield for 2(or 85%yield for 3).In this Letter,we will explore the structural require-ments of the phenol component that increase the lability of the O -benzyl phenol ether bond in the presence of TFA.In addition,0040-4039/$-see front matter Crown Copyright Ó2008Published by Elsevier Ltd.All rights reserved.*Tel.:+19058285354;fax:+19058285425(P.T.G.).E-mail addresses:steven.ﬂetcher@utoronto.ca (S.Fletcher),patrick.gunning@utoronto.ca (P.T.Gunning).Tetrahedron Letters 49(2008)4817–4819Contents lists available at ScienceDirectTetrahedron Lettersj o ur na l h om e pa ge :w w w.e ls e v ie r.c o m/lo c at e/t et l e twe will explore the selectivity of this mild debenzylation tech-nique with respect to other aromatic ethers and examine the sta-bility of other benzyl-based protecting groups to these reaction conditions.A series of 12O -benzyl-protected phenols was prepared by standard procedures in near quantitative yields.Each of these ethers was then deprotected with a 1:1mixture of TFA/toluene;our observations are summarized in Table 1.In certain cases,O ?C benzyl migration (Friedel–Crafts reaction)by-products (610%)were occasionally inseparable from the product by silica gel ﬂash column chromatography.Thus,several benzyl cation cap-tors were investigated for their abilities to improve yields and puri-ties of the debenzylation reactions.Three to ten equivalents of p -cresol,anisole and triethylsilane were employed,but these exerted little effects on reducing by-product formation.Conversely,we dis-covered that including the more nucleophilic scavenger thioanisole as an additive to the co-solvent toluene typically,after silica gel ﬂash column chromatography,furnished products in P 95%puri-ties (and higher yields),as judged by 1H NMR.Nevertheless,we envisaged any Friedel–Crafts impurities would be more readily separable on slightly more complex aryl benzyl ethers,as we ob-served with the substrates shown in Scheme 1and Tables 3and 4(>99%purities (1H NMR)in each case).Whilst likely leading to even higher yields and purities,large excesses of thioanisole (50equiv)are also known to accelerate TFA-mediated debenzyla-tion.10However,in our hands just 3equiv of thioanisole had little effect on the rate of debenzylation,allowing us to attribute the deprotection rates solely to the structure of the phenol.Electron-rich phenols are good scavengers of benzyl cations,13and since preliminary experiments with electron-rich phenols generated complex mixtures of Friedel–Crafts by-products under these deb-enzylation conditions,we chose to investigate only electron-poor phenols in this study.O -Benzyl-protected phenols with p -ortho -electron-withdraw-ing groups (6a ,6b ,6d ,6f )were swiftly (several in less than 3h cf.24h for unsubstituted phenol 6l )and cleanly debenzylated,with less than 5%of the undesired C-benzylated phenol by-prod-ucts.In contrast,meta -and para -electron-withdrawing groups slo-wed down the debenzylation (e.g.,entries 6g and 6h ),relative to the control compound 6l ,which itself could only be obtained in moderate purity by this method.The r -withdrawing (and p -donating)bromophenols 6i –k were insufﬁciently deactivated to benzyl cation scavenging and were contaminated with several by-products.Importantly,n -butyl benzyl ether 8was unaffected by TFA under the reaction conditions,indicating this procedure is selective for aryl benzyl ethers.In addition,the results in Table 1suggest that this procedure is suitable only for phenols substituted with p -electron-withdrawing groups.Since the debenzylation mechanism with TFA proceeds via an initial protonation of the phenol ether oxygen,the more available the ether oxygen lone pairs are,the faster the reaction will be.Hence,the slower reaction times for the phenols bearing meta -and para -electron-withdrawing groups make sense,although this is not true for the ortho -functionalized aryl benzyl ethers.As hypothesized for the bis-benzyl salicylate derivative 2earlier,we considered these ortho -substituted phenols were capable of chelat-ing the acidic hydrogen atom from TFA which therein facilitated the acid-mediated debenzylation via a six-membered cyclic inter-mediate,as proposed in Scheme 2.A similar chelation intermediate has been put forward by Baldwin and Haraldsson to account for the Lewis acid MgBr 2-mediated debenzylation of aromatic benzyl ethers ortho to an aldehyde group.14Accordingly,to test this hypothesis we expanded this series of ortho -substituted aryl benzyl ethers,and the results from their deb-enzylation reactions with TFA are summarized in Table 2.These substrates have been listed in order of increasing approximateTable 1TFA-mediated debenzylation of O -benzyl-protected phenols aTFAtolueneOBnROHR67Substrate RTime (h)b Yield c (%)6a o -CO 2Me,m d -NHAc 5min 936b o -CO 2Me 5min 946c p -CO 2Me 36e 63(85f )6d o -CO 2Bn 5min 936e p -CO 2Bn 36e 58(79f )6f o -NO 23976g m -NO 236e 75(98f )6h p -NO 236e 66(98f )6i o -Br 16—g 6j m -Br 30—g 6k p -Br 36—g 6lH 24—gn -BuOBn (8)—24No reactionaThe reaction was carried out with 6(0.5mmol)in a 1:1mixture of TFA/toluene (5ml)at rt,with 3equiv of thioanisole.bTime taken for all starting material to be consumed.cIsolated yield after silica gel ﬂash column chromatography.dmeta to phenol oxygen AND para to ester.eReaction was slow and incomplete after 3days.fYield based on recovered starting material.gComplex mixture of products.Table 2TFA-mediated debenzylation of O -benzyl-protected,ortho -substituted phenols aTFA tolueneOBnOH67RRSubstrate R p K aH b Time c (h)Yield d (%)Relative rate 6m CO 2NH 2À2248316n CHO À7 3.594e 6.96o CO 2H À8191246b CO 2Me À8.55min 942886d CO 2Bn À8.55min 932886p CN À10>4851(95f )—6f NO 2À1239786i Br —16—g 1.56lH—24—g1aThe reaction was carried out with 6(0.5mmol)in a 1:1mixture of TFA/toluene (5ml)at rt,with 3equiv of thioanisole.bApproximate p K aH of conjugate acid of R group.15cTime taken for all starting material to be consumed.dIsolated yield after silica gel ﬂash column chromatography.eIncluding thioanisole in the deprotection of 6n led to further by-products,thus no scavenger was used and compound 7n could be obtained in only 90%purity.fYield based on recovered starting material.gComplex mixture of products.4818S.Fletcher,P.T.Gunning /Tetrahedron Letters 49(2008)4817–4819acidity of the conjugate acid (decreasing p K aH )of the ortho -elec-tron-withdrawing substituent.15There appears to be an optimal p K aH of around À8.5,that is exhibited by carboxylic esters,which lead to the fastest rate of debenzylation with TFA.In an approxi-mate bell-shaped distribution of reaction rate versus ortho -substi-tuent p K aH —that was interrupted only by ortho -cyanophenol 6p —protonatable groups with p K aH ’s <À8.5or >À8.5were less effective at accelerating the TFA-mediated debenzylation.These data concur with our chelation hypothesis:groups that are too ba-sic bind more strongly to the TFA proton making it less available for sharing with,and ultimately releasing to,the phenol ether oxygen;groups that are weakly basic do not bind the TFA proton as well,leading to reduced chelation and hence less rate enhancement.The anomalous result for ortho -cyanophenol 6p was anticipated since this compound was selected as a negative control.Phenol 6p is geometrically incapable of chelating a proton,because the lin-ear,sp -hybridized nitrile functionality directs its basic nitrogen atom (p K aH %À10)away from the phenol oxygen.As predicted,there was no rate enhancement for the TFA-mediated debenzyla-tion of 6p relative to phenol 6l .In fact,6p was only slowly deben-zylated,at a rate that was comparable with the m -nitro and p -nitro derivatives 6g and 6h ,respectively.We next wanted to investigate the selectivity for the deprotec-tion of the benzyl group over other phenol protecting groups.Accordingly,the benzyl group in salicylate derivative 9a was varied with para -methoxybenzyl (PMB;9b ),methyl (9c ),allyl (9d )and iso -propyl (i -Pr;9e ).These substrates were then debenzylated with a 1:1mixture of TFA/toluene;our ﬁndings are reported in Table 3.Any impurities this time were minor and readily separable from the products,eliminating the need for the additive thioanisole.The relative rates at which these protecting groups were removed was para -methoxybenzyl >benzyl >allyl >iso -propyl )methyl,which reﬂects the stability of the carbocations.These data suggest that in salicylates such as 9,the benzyl phenol protecting group (R =Bn)can be removed with TFA in the presence of the corres-ponding allyl,iso -propyl and methyl ethers.Finally,we explored the selectivity of this mild debenzylation technique over other benzyl-based protecting groups,as shown in Table 4.As the results demonstrate,it was possible to deblock the O -benzyl ether in the presence of a benzyl ester (6d )and in the presence of a benzyl carbamate (11b ),thereby increasing the orthogonality of O -benzyl phenol ethers of salicylate derivatives.Interestingly,it was even possible to cleave the benzyl group in 11c with TFA in the presence of an N -Boc-protected aniline.In summary,we have presented the mild,efﬁcient and rapid deblocking of ortho -substituted aryl benzyl ethers with TFA.Deb-enzylation was fastest when the ortho group was a carboxylic ester,which we have attributed to a proton chelation effect.Other ortho groups that accelerated the TFA-mediated debenzylation included carboxylic acid,aldehyde and nitro.In addition,we have shown that in such ortho -functionalized phenols,benzyl could be removed in the presence of the corresponding iso -propyl,allyl and methyl ethers.Moreover,the benzyl ether could be selectively cleaved in the presence of benzyl ester,Cbz carbamate and Boc carbamate functionalities.AcknowledgementsThe authors gratefully acknowledge ﬁnancial support for this work from the Canadian Foundation of Innovation and the Univer-sity of Toronto (Connaught Foundation).References and notes1.Zhang,S.;Zhang,Z.-Y.Drug Discov.Today 2007,12,373–381.2.(a)Pei,Z.;Li,X.;Liu,G.;Abad-Zapatero,C.;Lubben,T.;Zhang,T.;Ballaron,S.J.;Hutchins,C.W.;Trevillyana,J.M.;Jirouseka,M.R.Bioorg.Med.Chem.Lett.2003,13,3129–3132;(b)Xin,Z.;Liu,G.;Abad-Zapatero,C.;Pei,Z.;Szczepankiewicz,B.G.;Li,X.;Zhang,T.;Hutchins,C.W.;Hajduk,P.J.;Ballaron,S.J.;Stashko,M.A.;Lubben,T.H.;Trevillyana,J.M.;Jirouseka,M.R.Bioorg.Med.Chem.Lett.2003,13,3947–3950.3.Tautz,L.;Bruckner,S.;Sareth,S.;Alonso,A.;Bogetz,J.;Bottini,N.;Pellecchia,M.;Mustelin,T.J.Biol.Chem.2005,280,9400–9408.4.Shrestha,S.;Bhattarai,B.R.;Chang,K.J.;Leea,K.-H.;Choa,H.Bioorg.Med.Chem.Lett.2007,17,2760–2764.5.Liljebris,C.;Larsen,S.D.;Ogg,D.;Palazuk,B.J.;Bleasdale,J.E.J.Med.Chem.2002,45,1785–1798.6.Siddiquee,K.;Zhang,S.;Guida,W.C.;Blaskovich,M.A.;Greedy,B.;Lawrence,H.R.;Yip,M.L.R.;Jove,R.;Laughlin,M.M.;Lawrence,N.J.;Sebti,S.M.;Turkson,J.Proc.Natl.Acad.Sci.U.S.A.2007,104,7391–7396.7.Pandey,P.N.;Purkayastha,M.L.Synthesis 1982,876–878.8.(a)Greene,T.W.;Wuts,P.G.M.Protective Groups in Organic Synthesis ,3rd ed.;John Wiley &Sons:New York,1999;(b)Kocienski,P.J.Protecting Groups ,3rd ed.;Georg Thieme:Stuttgart,Germany,2003.9.Kiso,Y.;Isawa,H.;Kitagawa,K.;Akita,T.Chem.Pharm.Bull.1978,26,2562–2564.10.Kiso,Y.;Ukawa,K.;Nakamura,S.;Ito,K.;Akita,T.Chem.Pharm.Bull.1980,28,673–676.11.Ploypradith,P.;Cheryklin,P.;Niyomtham,N.;Bertoni,D.R.;Ruchirawat,.Lett.2007,9,2637–2640.12.Marsh,J.P.,Jr.;Goodman,.Chem.1965,30,2491–2492.13.(a)Eberle,A.N.J.Chem.Soc.,Perkin Trans.11986,361–367;(b)Bodanszky,M.;Tolle,J.C.;Deshmane,S.S.;Bodanszky,A.Int.J.Pept.Protein Res.1978,12,57–68.14.Haraldsson,G.G.;Baldwin,J.E.Tetrahedron 1997,53,215–224.15.(a)Ionization Constants of Organic Acids in Solution ;Serjeant,E.P.,Dempsey,B.,Eds.IUPAC Chemical Data Series No.23;Pergamon Press:Oxford,UK,1979;(b)see also:/labs/evans/pdf/evans_pKa_table.pdf .Table 3TFA-mediated deprotection of O-blocked phenol ether derivatives of methyl 4-acetamidosalicylate aTFAtolueneNHAcNHAcORO OMeOH OMeO 910Substrate R Time b (h)Yield c (%)9a Bn 5min 919b PMB 2min 909c Me 480d 9d Allyl 20919ei -Pr3692aThe reaction was carried out with 9(0.5mmol)in a 1:1mixture of TFA/toluene (5ml)at rt.bTime taken for all starting material to be consumed.cIsolated yield after silica gel ﬂash column chromatography.dOnly starting material remained after 48h,at which point the reaction was aborted.Table 4Selectivity investigation into the TFA-mediated debenzylation of aryl benzyl ethers aTFA tolueneOBnOH2Bn2Bn1112RRSubstrate R Yield b (%)6d c H 9311a NHAc 9211b NHCbz 9311c dNHBoc54aThe reaction was carried out with 11(0.5mmol)in a 1:1mixture of TFA/toluene (5ml)at rt for 5min,then all solvents were evaporated.bIsolated yield after silica gel ﬂash column chromatography.cFor compound 6d ,3equiv of thioanisole were also used.dAfter 5min,the reaction mixture was diluted with CH 2Cl 2and then immedi-ately neutralized with 1M NaOH.The organic layer was then separated and evaporated.S.Fletcher,P.T.Gunning /Tetrahedron Letters 49(2008)4817–48194819。

赛庚啶

抗凝血、抗过敏类新药。可用于荨麻疹、湿疹、过敏性和接触性皮炎、皮肤瘙痒等过敏反应。
药物说明
01
分类
02
剂型
04
药代动力学
06
禁忌症03药理作用来自05适应症01
用法用量
02
注意事项
04
不良反应
03
药物相互作用
05
中毒
06
专家点评
抗变态反应药物 >抗组胺药
1.片剂：每片2mg，4mg。 2.霜剂:0.5%（盐酸盐）。
新用途
01
流行性腮腺炎
02
小儿厌食
03
支气管哮喘
04
小儿喘息性支气管炎
06
倾倒综合症
05
闭经-泌乳综合症
肝病性瘙痒
治疗偏头痛
内耳眩晕症
盐酸赛庚啶片
有人发现，扑尔敏合用西咪替丁治疗流行性腮腺炎，具有良好疗效，并证明盐酸赛庚啶的H1拮抗作用比扑尔敏强5倍以上。由此试用盐酸赛庚啶4～12毫克/天（随年龄调整）和西咪替丁20毫克/(千克·天)，分次口服，共 4～7天。结果：治疗9例中，痊愈者8例，治愈率为88.89%。平均退热时间及腮腺消肿时间，明显优于服用病毒唑、板蓝根外加敷中药者。
用法：口服，2毫克/次，3次/天，以后每日增加2毫克，逐渐增加至12～20毫克/天，6个月为1个疗程，停药 3～4周后开始下1个疗程。一般用药2周内见效。预防用药可在服药后30分钟发挥作用。
淤胆型肝炎、胆汁性肝硬化、肝炎后肝硬化等患者，常产生难以忍受的皮肤瘙痒，影响入眠和康复，常用抗过敏剂多难奏效。采用赛庚啶治疗8例淤胆性肝炎并严重瘙痒，经用激素、扑尔敏等无效者，改服赛庚啶，4毫克 /次，3次/天，温开水送服。一般服药3天后症状改善，总有效率为87.5%。

A review of chitin and chitosan applications

2M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–27radability,non-toxicity,adsorption properties,etc.Recently,much attention has been paid tochitosan as a potential polysaccharide resource[5].Although several efforts have been reportedto prepare functional derivatives of chitosan bychemical modiﬁcations[6–8],very few attainedsolubility in general organic solvents[9,10]andsome binary solvent systems[11–13].Chemi-cally modiﬁed chitin and chitosan structuresresulting in improved solubility in general or-ganic solvents have been reported by manyworkers[14–23].The present review is anattempt to discuss the current applications andfuture prospects of chitin and chitosan.2.Processing of chitin and chitosanChitin is easily obtained from crab or shrimpshells and fungal mycelia.In theﬁrst case,chitin production is associated with food indus-Fig.1.Structures of cellulose,chitin and chitosan.tries such as shrimp canning.In the second case,the production of chitosan–glucan complexes is chitin,chitosan and their derivatives.However,associated with fermentation processes,similar these naturally abundant materials also exhibit a to those for the production of citric acid from limitation in their reactivity and processability Aspergillus niger,Mucor rouxii,and Strep-[3,4].In this respect,chitin and chitosan are tomyces,which involves alkali treatment yield-recommended as suitable functional materials,ing chitosan–glucan complexes.The alkali re-because these natural polymers have excellent moves the protein and deacetylates chitin simul-properties such as biocompatibility,biodeg-taneously.Depending on the alkali concentra-Scheme1.M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–273 tion,some soluble glycans are removed[24]. 4.Properties of chitin and chitosanThe processing of crustacean shells mainlyMost of the naturally occurring polysac-involves the removal of proteins and the disso-charides,e.g.cellulose,dextran,pectin,alginic lution of calcium carbonate which is present inacid,agar,agarose and carragenans,are neutral crab shells in high concentrations.The resultingchitin is deacetylated in40%sodium hydroxide or acidic in nature,whereas chitin and chitosan at1208C for1–3h.This treatment produces are examples of highly basic polysaccharides. 70%deacetylated chitosan(Scheme1).Their unique properties include polyoxysaltformation,ability to formﬁlms,chelate metalions and optical structural characteristics[29].3.Economic aspects Like cellulose,chitin functions naturally as astructural polysaccharide,but differs from cellu-The production of chitin and chitosan islose in its properties.Chitin is highly hydro-currently based on crab and shrimp shellsphobic and is insoluble in water and most discarded by the canning industries in Oregon,organic solvents.It is soluble in hexaﬂuoro-Washington,Virginia and Japan and by variousisopropanol,hexaﬂuoroacetone,chloroalcohols ﬁnishingﬂeets in the Antarctic.Several coun-in conjugation with aqueous solutions of miner-tries possess large unexploited crustacean re-al acids[24]and dimethylacetamide containing sources,e.g.Norway,Mexico and Chile[25].5%lithium chloride.Chitosan,the deacetylated The production of chitosan from crustaceanproduct of chitin,is soluble in dilute acids such shells obtained as a food industry waste isas acetic acid,formic acid,etc.Recently,the gel economically feasible,especially if it includesforming ability of chitosan in N-methylmor-the recovery of carotenoids.The shells containpholine N-oxide and its application in controlled considerable quantities of astaxanthin,a carot-drug release formulations has been reported enoid that has so far not been synthesized,and[30–32].The hydrolysis of chitin with concen-which is marketed as aﬁsh food additive intrated acids under drastic conditions produces aquaculture,especially for salmon.relatively pure D-glucosamine.To produce1kg of70%deacetylatedThe nitrogen content of chitin varies from5 chitosan from shrimp shells,6.3kg of HCl andto8%depending on the extent of deacetylation, 1.8kg of NaOH are required in addition towhereas the nitrogen in chitosan is mostly in the nitrogen,process water(0.5t)and coolingform of primary aliphatic amino groups. water(0.9t).Important items for estimating theChitosan,therefore,undergoes reactions typical production cost include transportation,whichof amines,of which N-acylation and Schiff varies depending on labor and location.In India,reaction are the most important.Chitosan de-the Central Institute of Fisheries Technology,Kerala,initiated research on chitin and chitosan.rivatives are easily obtained under mild con-From their investigation,they found that dry ditions and can be considered as substituted prawn waste contained23%and dry squilla glucans.contained15%chitin[26].They have also N-Acylation with acid anhydrides or acyl reported that the chitinous solid waste fraction halides introduces amido groups at the chitosan of the average Indian landing of shellﬁsh nitrogen.Acetic anhydride affords fully ranges from60000to80000tonnes[27,28].acetylated chitins.Linear aliphatic N-acyl Chitin and chitosan are now produced commer-groups above propionyl permit rapid acetylation cially in India,Japan,Poland,Norway and of hydroxyl groups.Higher benzoylated chitin is Australia.The worldwide price of chitosan(in soluble in benzyl alcohol,dimethylsulfoxide, small quantities)is $7.5/10g(Sigma and formic acid and dichloroacetic acid.The N-Aldrich price list).hexanoyl,N-decanoyl and N-dodecanoyl deriva-4M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–27tives have been obtained in methanesulfonic the universally accepted non-toxic N-de-acid[33,34].acetylated derivative of chitin,where chitin is At room temperature,chitosan forms al-N-deacetylated to such an extent that it becomes dimines and ketimines with aldehydes and soluble in dilute aqueous acetic and formic ketones,respectively.Reaction with ketoacids acids.In chitin,the acetylated units prevail followed by reaction with sodium borohydride(degree of acetylation typically0.90).Chitosan produces glucans carrying proteic and non-is the fully or partially N-deacetylated derivative proteic amino groups.N-Carboxymethyl of chitin with a typical degree of acetylation of chitosan is obtained from glyoxylic acid.Exam-less than0.35.To deﬁne this ratio,attempts ples of non-proteic amine acid glucans derived have been made with many analytical tools from chitosan are the N-carboxybenzyl[35–44],which include IR spectroscopy, chitosans obtained from o-and p-phthalal-pyrolysis gas chromatography,gel permeation dehydic acids[24,25].Chitosan and simple chromatography and UV spectrophotometry,1 aldehydes produce N-alkyl chitosan upon hydro-ﬁrst derivative of UV spectrophotometry,H-13genation.The presence of the more or less NMR spectroscopy,C solid state NMR,ther-bulky substituent weakens the hydrogen bonds mal analysis,various titration schemes,acid of chitosan;therefore N-alkyl chitosans swell in hydrolysis and HPLC,separation spectrometry water in spite of the hydrophobicity of the alkyl methods and,more recently,near-infrared spec-chains,but they retain theﬁlm forming property troscopy[45].of chitosan[1].4.1.2.Molecular weightChitosan molecular weight distributions have 4.1.Physical and chemical characterizationbeen obtained using HPLC[46].The weight-The structural details of cellulose,chitin and average molecular weight(M)of chitin andwchitosan are shown in Fig. 1.Cellulose is a chitosan has been determined by light scattering homopolymer,while chitin and chitosan are[47].Viscometry is a simple and rapid method heteropolymers.Neither random nor block for the determination of molecular weight;the orientation is meant to be implied for chitin and constants a and K in the Mark–Houwink chitosan.The properties of chitin and chitosan equation have been determined in0.1M acetic such as the origin of the material(discussed in acid and0.2M sodium chloride solution.The the previous section),the degree of N-deacetyla-intrinsic viscosity is expressed astion,molecular weight and solvent and solutionproperties are discussed in brief.Glycol chitin,a[h]5KM51.81310Ma230.93partially O-hydroxyethylated chitin,was theﬁrst derivative of practical importance;otherThe charged nature of chitosan in acid solvents derivatives and their proposed uses are shown inand chitosan’s propensity to form aggregation Table1.complexes require care when applying theseconstants.Furthermore,converting chitin into 4.1.1.Degree of N-acetylationchitosan lowers the molecular weight,changesthe degree of deacetylation,and thereby alters An important parameter to examine closely isthe charge distribution,which in turn inﬂuences the degree of N-acetylation in chitin,i.e.thethe agglomeration.The weight-average molecu-ratio of2-acetamido-2-deoxy-D-glucopyranose66lar weight of chitin is1.03310to2.5310, to2-amino-2-deoxy-D-glucopyranose structuralbut the N-deacetylation reaction reduces this to units.This ratio has a striking effect on chitin55solubility and solution properties.Chitosan is1310to5310[48].M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–275 Table1Chitin derivatives and their proposed usesDerivative Examples Potential usesN-Acyl chitosans Formyl,acetyl,propionyl,butyryl,hexanoyl,Textiles,membranesoctanoyl,decanoyl,dodecanoyl,tetradecanoyl,and medical aidslauroyl,myristoyl,palmitoyl,stearoyl,benzoyl,monochloroacetoyl,dichloroacetyl,triﬂuoroacetyl,carbamoyl,succinyl,acetoxybenzoylN-Carboxyalkyl N-Carboxybenzyl,glycine-glucan(N-carboxy-Chromatographic (aryl)chitosans methyl chitosan),alanine glucan,phenylalanine media and metalglucan,tyrosine glucan,serine glucan,glutamic ion collectionacid glucan,methionine glucan,leucine glucanN-Carboxyacyl From anhydrides such as maleic,itaconic,acetyl-?chitosans thiosuccinic,glutaric,cyclohexane1,2-dicarbox-ylic,phthalic,cis-tetrahydrophthalic,5-norbo-rnene-2,3-dicarboxylic,diphenic,salicylic,tri-mellitic,pyromellitic anhydrideo-Carboxyalkyl o-Carboxymethyl,crosslinked o-carboxymethyl Molecular sieves, chitosans viscosity builders,and metal ion collec-tionSugar derivatives1-Deoxygalactic-1-yl-,1-deoxyglucit-1-yl-,?1-deoxymelibiit-1-yl-,1-deoxylactit-1-yl-,1-deoxylactit-1-yl-4(2,2,6,6-tetramethylpiperidine--1-oxyl)-,1-deoxy-69-aldehydolactit-1-yl-,1-deoxy-69-aldehydomelibiit-1-yl-,cellobiit-1-yl-chitosans,products obtained from ascorbic acidMetal ion chelates Palladium,copper,silver,iodine Catalyst,photography,health products,andinsecticides Semisynthetic resins Copolymer of chitosan with methyl methacrylate,Textilesof chitosan polyurea-urethane,poly(amideester),acrylamide-maleic anhydrideNatural polysacchar-Chitosan glucans from various organisms Flocculation andide complexes,metal ion chelation miscellaneous Alkyl chitin,benzyl chitin Intermediate,serineprotease puriﬁcationHydroxy butyl chitin,cyanoethyl chitosan Desaltingﬁltration,dialysis and insulatingpapersHydroxy ethyl glycol chitosan Enzymology,dialysisand special papersGlutaraldehyde chitosan EnzymeimmobilizationLinoelic acid–chitosan complex Food additive andanticholesterolemicUracylchitosan,theophylline chitosan,adenine-chitosan,chitosan salts of acid polysaccharides,chitosan streptomycin,2-amido-2,6-diaminohep-tanoic acid chitosan6M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–274.1.3.Solvent and solution properties theﬁrst solutions of chitin that could be formed Both cellulose and chitin are highly crys-into a‘ropy-plastic’state in1926.He prepared talline,intractable materials and only a limited the solution using inorganic salts capable of number of solvents are known which are applic-strong hydration[49],such as LiCNS, able as reaction solvents.Chitin and chitosan Ca(CNS),CaI,CaBr,CaCl,etc.After this2222degrade before melting,which is typical for report,many solvent systems including organic polysaccharides with extensive hydrogen bond-solvents and mixtures of inorganic salts and ing.This makes it necessary to dissolve chitin organic solvents came into existence.and chitosan in an appropriate solvent system to To help the dissolution of chitin,it was N-impart functionality.For each solvent system,deacetylated in5%caustic soda at608C for14 polymer concentration,pH,counterion concen-days[50].Another procedure for N-deacetyla-tration and temperature effects on the solution tion was to place the chitin in an autoclave for3 viscosity must be parative data h at1808C and10atm pressure.It was pointed from solvent to solvent are not available.As a out that6to10%of solids of N-deacetylated general rule,the maximum amount of polymer chitin can be brought into acidic solution at is dissolved in a given solvent towards a room temperature.Aqueous acetic acid was homogeneous solution.Subsequently,the poly-found to be suitable for this purpose.mer is regenerated in the required form(dis-After passing the polymer solutions through a cussed in the following sections).A coagulant isﬁlter press to remove impurities,ﬁbres were required for polymer regeneration or solidiﬁca-spun.Chemicals incompatible with chitin were tion.The nature of the coagulant is also highly suggested as coagulants.The resultantﬁbres dependent on the solvent and solution properties were washed and dried under tension.Theﬁnal as well as the polymer used[54,75].productﬁbres had a round-to heart-shapedcross section with a tensile breaking load of352kg/mm(345Pa).Theﬁbres possessed a dull 5.Chitin and its derivatives inﬁbre luster similar to natural silk,leading to the formation suggestion that the N-deacetylated chitinﬁbreswould make good artiﬁcial hair.The collection 5.1.Natural microﬁbriller arrangementand recycling of chitin from small-scale con-sumers was also suggested.Clark and Smith Chitin has been known to form microﬁbrillarreported a procedure for producingﬁbres by arrangements in living organisms.Theseﬁbrilsdissolution of chitin at958C in presaturated are usually embedded in a protein matrix andsolutions of lithium thiocyanate(saturated608C) have diameters from2.5to2.8nm.Crustacean[51].No tensile properties or solution concen-cuticles possess chitin microﬁbrils with diame-trations were reported.However,X-ray analysis ters as large as25nm.The presence of mi-showed a high degree of orientation.Solvent croﬁbrils suggests that chitin has characteristicsremoval was not successful even at2008C. which make it a good candidate forﬁbreLithium iodide was implied to have behaved in spinning.To spin chitin or chitosanﬁbres,thethe same manner.A ratio of5mol lithium raw polymer must be suitably redissolved afterthiocyanate per mole anhydroglucose unit was removal of extraneous material such as calciumfound to exist.This is comparable to the carbonate and proteins,which encase the mi-cellulose–lithium thiocyanate compound.Cellu-croﬁbrils.lose solubility and the role of solvate/saltcomplexes have been reviewed in detail[52,53].5.2.Fibre formation—in retrospectionRecently,Rathke and Hudson published a re-Numerous methods of spinning chitinﬁbres view highlighting the ability of chitin and have been reported since Von Weimarn reported chitosan asﬁbre andﬁlm formers[54].M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–277 5.3.Novel solvent spin systems suggested as well as dissolution below roomtemperature.Fibres were extruded through a 5.3.1.Halogenated solvent spin system spinneret of0.04and0.06mm diameter into an In1975,Austin suggested organic solvents acetone coagulation bath followed by a metha-containing acids for the direct dissolution of nol bath.The tensile strength of driedﬁlaments chitin.Such a system was chloroethanol and was in the range of1.67to3.1g/d with an sulfuric acid.The precipitation of chitin in elongation from8.7to20.0%.The strength of ﬁbrillar form in water,methanol,or aqueous theﬁbres was improved by leaving them in a ammonium hydroxide was mentioned,but no0.5g/l aqueous caustic soda solution for1h.ﬁbre tensile data were presented[55].The resultant tensile strengths were2.25to3.20In1975,Brine and Austin suggested tri-g/d with elongations of19.2to27.3%,respec-chloroacetic acid(TCA)as a chitin solvent.tively[57].Kifune and co-workers further sug-Chitin was pulverized and two parts by weight gested that these chitinﬁlaments were suitablewere added to87parts by weight of a solvent as absorbable surgical suture[58].However,mixture containing40%TCA,40%chloral TCA is very corrosive and degrades the poly-hydrate(US Department of Justice,Drug En-mer molecular weight.The breaking elongationsforcement Agency,class IV controlled sub-suggest that the halogenated solvents act asstance),and20%methylene chloride over a plasticizers.period of30–45min.Aﬁlament was extruded Fuji Spinning Company dissolved chitosan infrom this solution using a hypodermic needle a mixture of water and dichloroacetic acidand acetone as the coagulant.Theﬁlament was(DCA).The6.44%chitosan acetate salt solutionthen neutralized with potassium hydroxide viscosity was410poise.The dope was extruded(KOH)in2-propanol followed by washing in through a platinum nozzle(30holes of0.2mmdeionized water.Theﬁlaments were then cold diameter each)into basic CuCO–(NH)OH34 drawn.Two tensile breaks were taken at60%solution to formﬁbres.Denier and tensilerelative humidity and room temperature.The properties were not reported[59].ﬁrst was from aﬁlament with a cross section of Tokura and co-workers used a combination of0.0830.10mm,yielding a tensile strength of72formic acid(FA),DCA and diisopropyl ether as2kg/mm(710Pa)and a breaking elongation of a solvent system.Chitin was cycled several13%.The secondﬁlament had a cross section of times from2208C to room temperature in FA,0.01430.740mm,indicating a collapsed core followed by addition of a small amount ofstructure.It had a tensile strength of104kg/DCA.Diisopropyl ether was then added to 2mm(1026Pa)and a breaking elongation of reduce the solution viscosity to below199poise44%[56].Syringing aﬁlament cannot be and tensile properties were also reported[60].Itinterpreted as conclusive evidence for a possible is noteworthy that the wet strength drops towet spinning process.While syringe extrusion below0.50g/d but that the elongation increasesmight indicate the selection of a coagulant,it to13%.would be rather surprising to obtain meaningful A TCA/dichloromethane spin system is alsotensile data.Shear forces in a spinneret are described by the Unitika Co.Three parts chitinmuch greater than those experienced in a sy-were dissolved in50parts TCA and50partsringe tip.dichloromethane.The defoamed dope was ex-Kifune and co-workers suggested dissolving truded into acetone before wind-up.The bob-chitin in TCA and a chlorinated hydrocarbon bins were neutralized with KOH,washed withsuch as chloromethane,dichloromethane,and water,and dried.Theﬁbres had a tensile1,1,2-trichloroethane.The TCA concentration strength of2g/d and0.5–20denier[61].should be kept between25and75%.A con-Unitika Co.also used the TCA/chloral hy-centration range between1and10%chitin was drate/dichloroethane solvent system for chitin.8M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–27Five parts were dissolved in100parts of a4:4:2upon short exposures.Chlorohydrocarbons are TCA/chloral hydrate/dichloroethane solvent increasingly environmentally unacceptable sol-mixture and extruded through a0.06mm nozzle vents.Hexaﬂuoro-2-propanol and hexaﬂuoro-into acetone.Theﬁbres were treated with acetone sesquihydrate are toxic.Formic acid can methanolic NaOH.The optimumﬁbres gave a act as a sensitizer.tenacity of3.2g/d with an elongation of20%[62].Unitika Co.followed this up with another 5.3.2.Amide–LiCl systempatent using a60:40TCA/trichloroethylene In1978,Rutherford and Austin summarized spin dope mixture.Tensile properties were the problems encountered inﬁnding a solvent unavailable[63].In1983,Unitika Co.showed system for chitin[65].Austin suggested N,N-that a dope consisting of three parts chitin,50dimethylacetamide(DMAc)–5%LiCl or N-parts TCA,and50parts dichloromethane could methyl-2-pyrrolidone(NMP)–5%LiCl as sol-be spun at a rate of 1.7ml/min under25vents for chitin.A solution of5%w/v was 2kg/cm pressure into acetone to formﬁlaments.obtained within2h with these systems.A The extrusion die had holes of0.07mm diam-ﬁlament was extruded from the solution using a eter,indicating a jet velocity of8.8m/min and15-gauge needle into an acetone coagulation a take-up of5m/min.The coagulation bath was bath.This was followed by more washing and maintained at188C.Theﬁlaments were washed drawing in acetone.Theﬁnalﬁlament was with acetone at188C for10min,rewound at4.5washed in deionized water.Tensile properties m/min,then neutralized,washed and dried.The were obtained at60%R.H.and room tempera-multiﬁlament product had a total denier of150ture at an applied stress of0.1cm/min.The with a tenacity of 2.65g/d[63].A similar resultant dry tensile strengths for different crab system using four parts chitin in the same and shrimp species ranged from24to60kg/2solvent but a40-hole die of0.08mm diameter mm(236–592Pa)[66].each was also used.The jet velocity was10.4Russian researchers spun chitinﬁbres out of m/min into a258C acetone bath.A rewinding at DMAc/NMP solutions containing5%chitin 7m/min followed theﬁrst take-up roll at5and5%LiCl(based on chitin content).These m/min.The total denier was175;however,noﬁbres were drawn in a50:50ethanol/ethylene tensile properties were reported[64].glycol bath,giving an average yield strength of Some of the halogenated solvent systems390MPa with3%elongation.An initial attained dry tenacities of above3g/d;however,modulus of2GPa was also reported.Scanning the low wet tenacities were still undesirable.electron microscopy showedﬁbres with a round Although theﬁbre characterization was muchﬁbrillar cross section[67].A follow-up study better for these systems,the polymer characteri-showed a decrease in the elasticity modulus and zation lacked molecular weight as well as relative elongation with increase in the degree degree of N-acetylation formation.Solution of N-acetylation(12–30%).From X-ray analy-properties would be hard to obtain due to rapid sis,an increase in the amount of amorphous chitin degradation in these solvents.Although regions was observed with increase in degree of anhydrous coagulation baths were used and acetylation[68].compared,ﬁbres were neutralized in aqueous The amide–lithium systems showed some of media.A study in completely anhydrous sys-the best dry tenacities,although they still lack tems would be of interest,since it may lead to adequate wet tenacities.The low wet tenacities more densely consolidatedﬁbres.The im-are probably due to low crystallinity and poor plementation of these spin systems represents a consolidation of theﬁbre.Theﬁbres and spin problem due to the nature of the solvents.TCA dopes were well characterized but the polymers and DCA are corrosive and degrade the polymer used to prepare these dopes were not.SomeM.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–279 coagulation studies were carried out but a clear 6.1.Photographycomparison could not be made.A problem withChitosan has important applications in photo-this spin system is the removal and recovery ofgraphy due to its resistance to abrasion,its lithium from theﬁbre.The lithium acts as aoptical characteristics,andﬁlm forming ability. Lewis acid by solvating the chitin amide group.Silver complexes are not appreciably retained It is unclear if this can be completely reversedby chitosan and therefore can easily be pene-through washing,once theﬁbres are formed.trated from one layer to another of aﬁlm bydiffusion[70].5.3.3.Amine oxide/water systemAttempts have been made to develop a pro-6.2.Cosmeticscess for chitosanﬁbres by direct dissolutionusing a novel solvent system,N-methylmor-For cosmetic applications,organic acids are pholine oxide/water(NMMO/H O),but no2usually good solvents,chitin and chitosan have interesting tensile data were obtained from these fungicidal and fungistatic properties.Chitosan ispreliminary investigations[69].the only natural cationic gum that becomesviscous on being neutralized with acid.Thesematerials are used in creams,lotions and perma-6.Applications nent waving lotions and several derivatives havealso been reported as nail lacquers[78].The interest in chitin originates from thestudy of the behaviour and chemical characteris- 6.3.Chitosan as an artiﬁcial skintics of lysozyme,an enzyme present in humanbodyﬂuids[70].A wide variety of medical Individuals who have suffered extensive loss-applications for chitin and chitin derivatives es of skin,commonly inﬁres,are actually ill have been reported over the last three decades and in danger of succumbing either to massive [71–73].It has been suggested that chitosan infection or to severeﬂuid loss.Patients must may be used to inhibitﬁbroplasia in wound often cope with problems of rehabilitation aris-healing and to promote tissue growth and ing from deep,disﬁguring scars and crippling differentiation in tissue culture[74].contractures.Malette et al.studied the effect of The poor solubility of chitin is the major treatment with chitosan and saline solution on limiting factor in its utilization.Despite this healing andﬁbroplasia of wounds made by limitation,various applications of chitin and scalpel insertions in skin and subcutaneous modiﬁed chitins have been reported,e.g.as raw tissue in the abdominal surface of dogs[79]. material for man-madeﬁbres[54].Fibres made Yannas et al.proposed a design for artiﬁcial of chitin and chitosan are useful as absorb-skin,applicable to long-term chronic use,focus-able sutures and wound-dressing materials ing on a nonantigenic membrane,which per-[58,75,76].Chitin sutures resist attack in bile,forms as a biodegradable template for synthesis urine and pancreatic juice,which are problem of neodermal tissue[80].It appears that areas with other absorbable sutures[58].It has chitosan,having structural characteristics simi-been claimed that wound dressings made of lar to glycosamino glycans,could be considered chitin and chitosanﬁbres have applications in for developing such substratum for skin replace-wastewater treatment.Here,the removal of ment[81–83].heavy metal ions by chitosan through chelationhas received much attention[70,77].Their use 6.3.1.Chitin-and chitosan-based dressingsin the apparal industry,with a much larger Chitin and chitosan have many distinctive scope,could be a long-term possibility[78].biomedical properties.However,chitin-based10M.N.V.Ravi Kumar/Reactive&Functional Polymers46(2000)1–27wound healing products are still at the early is accelerated by the oligomers of degradedchitosan by tissue enzymes and this material stages of research[84].was found to be effective in regenerating the Sparkes and Murray[85]developed a sur-skin tissue in the area of the wound.gical dressing made of a chitosan–gelatin com-Biagini et al.[89]developed an N-carboxy-plex.The procedure involves dissolving thebutyl chitosan dressing for treating plastic chitosan in water in the presence of a suitablesurgery donor sites.A solution of N-carboxy-acid,maintaining the pH of the solution at aboutbutyl chitosan was dialyzed and freeze-dried to 2–3,followed by adding the gelatin dissolved in3produce a1032030.5cm soft andﬂexible water.The ratio of chitosan and gelatin is3:1topad,which was sterilized and applied to the 1:3.To reduce the stiffness of the resultingwound.This dressing could promote ordered dressing a certain amount of plasticizers such astissue regeneration compared to control donor glycerol and sorbitol could be added to thesites.Better histoarchitectural order,better vas-mixture.Dressingﬁlm was cast from thiscularization and the absence of inﬂammatory solution on aﬂat plate and dried at roomcells were observed at the dermal level,while temperature.It was claimed that,in contrast tofewer aspects of proliferation of the malpighian conventional biological dressings,this ex-layer were reported at the epidermal level. perimental dressing displayed excellent adhe-The British Textile Technology Group sion to subcutaneous fat.(BTTG)patented a procedure for making a Nara et al.[86]patented a wound dressingchitin-basedﬁbrous dressings[90–93].In this comprising a nonwoven fabric composed ofmethod the chitin/chitosanﬁbres were not made chitinﬁbres made by the wet spinning tech-by the traditionalﬁbre-spinning technique and nique.In one of the examples,chitin powderthe raw materials were not from shrimp shell was ground to100mesh and treated in1M HClbut from micro-fungi instead.The procedure for1h at48C.It was then heated to908C wherecan be summarized as follows.it was treated for3h in a0.3%NaOH solutionto remove calcium and protein in the chitin(i)Micro-fungal mycelia preparation from a powder,and rinsed repeatedly followed by culture of Mucor mucedo growing in a drying.The resultant chitin was dissolved in a nutrient solution.dimethylacetamide solution containing7wt%(ii)Culture washing and treatment with lithium chloride to form a7%dope.After NaOH to remove protein and precipitate ﬁltering and allowing defoaming to occur,the chitin/chitosan.dope was extruded through a nozzle of diameter(iii)Bleaching and further washing.0.06mm and200holes into butanol at608C at a(iv)Preparation of the dispersion ofﬁbres rate of2.2g/min.The chitin was coagulated using paper-making equipment.and collected at a speed of10m/min.The(v)Filtration and wet-laid matt preparation; resultant strand was rinsed with water and dried mixing with otherﬁbres to give mechanical to obtain aﬁlament of0.74dtex with a strength strength.of2.8g/den.Theﬁlaments were then cut intostapleﬁing poly(vinyl alcohol)as a This is a novel method,which uses a non-ﬁbrous binder,nonwoven dressings were made.animal source as the raw material,and the Kifune et al.[87]developed a new wound resulting micro-fungalﬁbres are totally different dressing,Beschitin W,composed of chitin non-from normal spunﬁbres.They have highly woven fabric which proved to be beneﬁcial in branched and irregular structures.Theﬁbres are clinical practice.Kim and Min[88]have de-unmanageably brittle when they are allowed to veloped a wound-covering material from poly-dry and a plasticizer has to be associated with electrolyte complexes of chitosan with sulfon-the whole process and a wet-laid matt is used as ated chitosan.It is proposed that wound healing the basic product.。

21cfr176.170 Tests for Paper and Paperborad

21 CFR Ch. I (4–1–05 Edition)§176.170films or grease-resistant papers con-form with appropriate food additive regulations.(c) The labeling of the food additive shall contain adequate directions for its use to insure compliance with the requirements of paragraphs (a) and (b) of this section.§176.170Components of paper and pa-perboard in contact with aqueous and fatty foods. Substances identified in this section may be safely used as components of the uncoated or coated food-contact surface of paper and paperboard in-tended for use in producing, manufac-turing, packaging, processing, pre-paring, treating, packing, transporting, or holding aqueous and fatty foods, subject to the provisions of this sec-tion. Components of paper and paper-board in contact with dry food of the type identified under Type VIII of table 1 in paragraph (c) of this section are subject to the provisions of §176.180. (a) Substances identified in para-graph (a) (1) through (5) of this section may be used as components of the food- contact surface of paper and paper-board. Paper and paperboard products shall be exempted from compliance with the extractives limitations pre-scribed in paragraph (c) of this section:Provided, That the components of the food-contact surface consist entirely of one or more of the substances identi-fied in this paragraph: And provided fur-ther, That if the paper or paperboard when extracted under the conditions prescribed in paragraph (c) of this sec-tion exceeds the limitations on extrac-tives contained in paragraph (c) of this section, information shall be available from manufacturing records from which it is possible to determine that only substances identified in this para-graph (a) are present in the food-con-tact surface of such paper or paper-board.(1) Substances generally recognized as safe in food.(2) Substances generally recognized as safe for their intended use in paper and paperboard products used in food packaging.(3) Substances used in accordance with a prior sanction or approval.(4) Substances that by regulation in parts 170 through 189 of this chapter may be safely used without extractives limitations as components of the uncoated or coated food-contact sur-face of paper and paperboard in contact with aqueous or fatty food, subject to the provisions of such regulation.(5) Substances identified in this para-graph, as follows:List of SubstancesLimitationsAcetyl peroxide ............................................................................For use only as polymerization catalyst.Acrylamide-methacrylic acid-maleic anhydride copolymers con-taining not more than 0.2 percent of residual acrylamide monomer and having an average nitrogen content of 14.9 percent such that a 1 percent by weight aqueous solution has a minimum viscosity of 600 centipoises at 75 °F, as de-termined by LVG-series Brookfield viscometer (or equivalent) using a No. 2 spindle at 30 r.p.m.For use only as a retention aid employed prior to the sheet- forming operation in the manufacture of paper and paper-board in such an amount that the finished paper and paper-board will contain the additive at a level not in excess of 0.05 percent by weight of dry fibers in the finished paper andpaperboard. Acrylamide-b -methacrylyloxyethyltrimethylammonium methyl sulfate copolymer resins containing not more than 10 molar percent of b -methacrylyloxyethyltrimethylammonium methyl sulfate and containing less than 0.2% of residual acrylamide monomer.For use only as a retention aid and flocculant employed prior to the sheet-forming operation in the manufacture of paper and paperboard. Acrylic acid, sodium salt copolymer with polyethyleneglycol allyl ether (CAS Reg. No. 86830–15–1).For use only in paper mill boilers. Acrylic acid copolymer with 2-acrylamido-2-methylpropane-sul-fonic acid (CAS Reg. No. 40623–75–4) and/or its ammo-nium/alkali metal mixed salts. The copolymer is produced by poly-merization of acrylic acid and 2-acrylamido-2- methylpropane-sulfonic acid in a weight ratio of 60/40, such that a 28 percent by weight aqueous solution of the polymer has a viscosity of 75–150 centipoises at 25 °C as deter-mined by LV-series Brookfield viscometer (or equivalent) using a No. 2 spindle at 60 r.p.m.For use only as a scale inhibitor prior to the sheet-forming op-eration in the manufacture of paper and paperboard andused at a level not to exceed 1.0 kilogram (2.2 pounds) of copolymer per 907 kilograms (1 ton) of dry paper and paper-board fibers.Food and Drug Administration, HHS§176.170List of SubstancesLimitationsAcrylonitrile polymer, reaction product with ethylenediamine sulfate having a nitrogen content of 22.5–25.0 percent (Kjel-dahl dry basis) and containing no more than 0.075 percent monomer as ethylenediamine. The finished resin in a 24 per-cent by weight aqueous solution has a viscosity of 1,000– 2,000 centipoises at 25 °C as determined by LVT-series Brookfield viscometer using a No. 4 spindle at 50 r.p.m. (or by other equivalent method).For use only as a size promoter and retention aid at a level not to exceed 0.5 percent by weight of the dry paper and paper-board. Acrylonitrile polymer with styrene, reaction product with ethyl-enediamine acetate, having a nitrogen content of 7.4–8.3 percent (Kjeldahl dry basis) and containing no more than 0.25 percent monomer as ethylenediamine. 1. For use only as a sizing material applied after the sheet- forming operation in the manufacture of paper and paper-board in such amount that the paper and paperboard will contain the additive at a level not in excess of 0.25 percentby weight of the dry paper and paperboard.2. For use only as a sizing material applied prior to the sheet- forming operation in the manufacture of paper and paper-board in such amount that the paper and paperboard will contain the additive at a level not in excess of 1.0 percent by weight of the dry paper and paperboard.1-Alkenyl olefins, containing not less than 72 percent of C 30 and higher olefins.For use only under the following conditions: 1. In coatings for paper and paperboard with food of Types I,II, IV-B, and VII-B described in table 1 of paragraph (c) of this section under conditions of use E, F, and G described in table 2 of paragraph (c) of this section.2. In coatings for paper and paperboard with food of Type VIII described in table I of paragraph (c) of this section under conditions of use A through H described in table 2 of para-graph (c) of this section.(2-Alkenyl) succinic anhydrides mixture, in which the alkenyl groups are derived from olefins which contain not less than 95 percent of C 15-C 21groups.For use only as a sizing agent employed prior to the sheet- forming operation in the manufacture of paper and paper-board and limited to use at a level not to exceed 1 percentby weight of the finished dry paper and paperboard fibers.Alkyl(C 12-C 20)methacrylatemethacrylic acid copolymers (CAS Reg. No. 27401–06–5).For use only as stabilizers employed prior to the sheet-forming operation in the manufacture of paper and paperboard. tert-Alkyl(C 8-C 16)mercaptans .......................................................For use only as polymerization-control agent. Aluminum acetate.2-Amino-2-methyl-1-propanol (CAS Reg. No. 124–68–5)..........For use as a dispersant for pigment suspension at a level notto exceed 0.25 percent by weight of pigment. The suspen-sion is used as a component of coatings for paper and pa-perboard under conditions of use described in paragraph (c) of this section, table 2, conditions of use E through G.Ammonium bis(N-ethyl-2-perfluoroalkylsulfonamido ethyl) phosphates, containing not more than 15% ammonium mono (N-ethyl-2-perfluoroalkylsulfonamido ethyl) phosphates, where the alkyl group is more than 95% C 8and the salts have a fluorine content of 50.2% to 52.8% as determined on a solids basis.For use only as an oil and water repellant at a level not to ex-ceed 0.17 pound (0.09 pound of fluorine) per 1,000 square feet of treated paper or paperboard of a sheet basis weight of 100 pounds or less per 3,000 square feet of paper or pa-perboard, and at a level not to exceed 0.5 pound (0.26 pound of fluorine) per 1,000 square feet of treated paper orpaperboard having a sheet basis weight greater than 100 lb. per 3,000 square feet as determined by analysis for total flu-orine in the treated paper or paperboard without correction for any fluorine that might be present in the untreated paper or paperboard, when such paper or paperboard is used as follows:1. In contact, under conditions of use C, D, E , F, G, or H de-scribed in table 2 of paragraph (c) of this section, with non-alcoholic food.2. In contact with bakery products of Type VII, VIII, and IX de-scribed in table I of paragraph (c) of this section under good manufacturing practices of commercial and institutional bak-ing.Ammonium persulfate.Ammonium thiosulfate.Ammonium zirconium carbonate (CAS Reg. No. 32535–84–5) and its tartaric acid adduct.For use only as an insolubilizer for binders used in coatings for paper and paperboard, and limited to use at a level not toexceed 2.5 percent by weight of coating solids.Ammonium zirconium citrate (CAS Reg. No. 149564–62–5), ammonium zirconium lactate-citrate (CAS Reg. No. 149564– 64–7), ammonium zirconium lactate (CAS Reg. No. 149564– 63–6).For use as insolubilizers with protein binders in coatings for paper and paperboard, at a level not to exceed 1.4 percent by weight of coating solids.21 CFR Ch. I (4–1–05 Edition) §176.170List of Substances LimitationsAnionic polyurethane, produced by reacting the preliminary adduct formed from the reaction of glyceryl monostearate and 2,4-toluenediisocyanate with not more than 10 mole per-cent N-methyldiethanolamine and not less than 90 mole per-cent dimethylolpropionic acid. The final product is a 15 to 20 percent by weight aqueous solution, having a Brookfield vis-cosity of 25 to 100 centipoises at 24 °C (75 °F).For use only as a surface sizing agent at a level not to exceed 0.1 percent by weight of dry paper and paperboard.9,10–Anthraquinone (Chemical Abstracts Service Registry No. 84–65–1) which has a purity of not less than 98 percent.For use only as a pulping aid in the alkaline pulping of lignocellulosic material at levels not to exceed 0.1 percent by weight of the raw lignocellulosic material.Aromatic petroleum hydrocarbon resin, hydrogenated (CAS Reg. No. 88526–47–0), produced by the catalytic polym-erization of aromatic substituted olefins from low boiling dis-tillates of cracked petroleum stocks with a boiling point no greater than 220 °C (428 °F), and the subsequent catalytic reduction of the resulting aromatic petroleum hydrocarbon resin. The resin meets the following specifications: softening point 85 °C (185 °F) minimum, as determined by ASTM Method E 28–67 (Reapproved 1982), ‘‘Standard Test Meth-od for Softening Point by Ring-and-Ball Apparatus,’’ and ani-line point 70 °C (158 °F) minimum, as determined by ASTM Method D 611–82, ‘‘Standard Test Methods for Aniline Point and Mixed Aniline Point of Petroleum Products and Hydro-carbon Solvents,’’ which are incorporated by reference in ac-cordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies may be obtained from the American Society for Testing and Materials, 1916 Race St., Philadelphia, PA 19103, or may be examined at the National Archives and Records Administra-tion (NARA). For information on the availability of this mate-rial at NARA, call 202–741–6030, or go to: http:// /federal l register/code l of l federal l regulations/ibr l locations.html..For use only as modifiers in wax polymer blend coatings for paper and paperboard at a level not to exceed 50 weight- percent of the coating solids under conditions of use E, F, and G identified in table 2 of paragraph (c) of this section.Azo-bisisobutyronitrile..................................................................For use only as polymerization catalyst.1,2-Benzisothiazolin-3-one (CAS Registry No. 2634–33–5).......For use only as a preservative in paper coating compositionsand limited to use at a level not to exceed 0.01 mg/in2(0.0016 mg/cm2) of the finished paper and paperboard. Benzoyl peroxide.........................................................................Do.N,N-Bis(2-hydroxyethyl)alkyl (C12-C18)amide..............................For use only as an adjuvant to control pulp absorbency andpitch content in the manufacture of paper and paperboardprior to the sheet forming operation.Bis(methoxymethyl)tetrakis-[(octadecyloxy)-methyl]melamine resins having a 5.8–6.5 percent nitrogen content (CAS Reg. No. 68412–27–1).For use only under the following conditions:1. As a water repellant employed prior to the sheet-forming op-eration in the manufacture of paper and paperboard in such amount that the finished paper and paperboard will contain the additive at a level not in excess of 1.6 percent by weight of the finished dry paper and paperboard fibers.2. The finished paper and paperboard will be used in contact with nonalcoholic foods only.3. As a water repellant employed after the sheet-forming oper-ation in the manufacture of paper and paperboard in such amount that the finished paper and paperboard will contain the additive at a level not to exceed 1.6 percent by weight of the finished dry paper and paperboard fibers. The finished paper and paperboard will be used only in contact with food of Types I, II, IV-B, VI, VII-B, and VIII described in table 1 of paragraph (c) of this section.2-Bromo-2-nitro-1,3-propanediol (CAS Reg. No. 52–51–7)........For use only as an antimicrobial/preservative in fillers, pigmentslurries, starch sizing solutions, and latex coatings at levelsnot to exceed 0.01 percent by weight of those components.Butanedioic acid, sulfo-1,4-di-(C9-C11alkyl) ester, ammonium salt (also known as butanedioic acid, sulfo-1,4-diisodecyl ester, ammonium salt [CAS Reg. No. 144093–88–9])..For use as a surface active agent in package coating inks at levels not to exceed 3 percent by weight of the coating ink.tert-Butyl hydroperoxide..............................................................For use only as polymerization catalyst.tert-Butyl peroxide.......................................................................Do.Calcium isostearate.....................................................................For use only with n-decyl alcohol as a stabilizing material foraqueous calcium stearate dispersions intended for use ascomponents of coatings for paper and paperboard. Carrageenan and salts of carrageenan as described in§§172.620 and 172.626 of this chapter.Castor oil, hydrogenated.Castor oil, sulfated, ammonium, potassium, or sodium salt.Cellulose, regenerated. Chloracetamide............................................................................For use only as polymerization-control agent.Cobaltous acetate........................................................................For use only as polymerization catalyst.Food and Drug Administration, HHS §176.170 List of Substances LimitationsCumene hydroperoxide...............................................................Do. Cyanoguanidine...........................................................................For use only:1. As a modifier for amino resins.2. As a fluidizing agent in starch and protein coatings for paperand paperboard.n-Decyl alcohol............................................................................For use only with calcium isostearate as a stabilizing materialfor aqueous calcium stearate dispersions intended for use ascomponents of coatings for paper and paperboard. Dialdehyde guar gum..................................................................For use only as a wet-strength agent employed prior to thesheet-forming operation in the manufacture of paper and pa-perboard and used at a level not to exceed 1% by weight ofthe finished dry paper and paperboard fibers.Dialdehyde locust bean gum.......................................................Do.Dialkyl(C16-C18)carbamoyl chloride (CAS Reg. No. 41319–54– 4) manufactured by the reaction of secondary amines de-rived from fatty acids of animal or vegetable sources with phosgene.For use as a sizing agent at a level not to exceed 0.2 percent by weight of the dry fiber.Diallyldimethyl ammonium chloride polymer with acrylamide and potassium acrylate, produced by copolymerizing either (1) diallyldimethyl ammonium chloride and acrylamide in a weight ratio of 50/50, with 4.4 percent of the acrylamide sub-sequently hydrolyzed to potassium acrylate or (2) polym-erized diallyldimethyl ammonium chloride, acrylamide and potassium acrylate (as acrylic acid) in a weight ratio of 50/ 47.8/2.2, respectively, so that the finished resin in a 1 per-cent by weight aqueous solution (active polymer) has a vis-cosity of more than 22 centipoises at 22 °C (72 °F) as deter-mined by LVF series, Brookfield Viscometer using No. 1 spindle at 60 RPM (or by other equivalent method) (CAS Reg. No. 25136–75–8).For use only as a retention and/or drainage aid employed prior to the sheet-forming operations in the manufacture of paper and paperboard and limited to use at a level not to exceed 0.05 percent by weight of the finished paper and paper-board.Diallyldimethylammonium chloride with acrylamide (CAS Reg. No. 26590–05–6). The copolymer is produced by copolym-erizing diallyldimethylammonium chloride with acrylamide in a weight ratio of 50–50 so that the finished resin in a 1 per-cent by weight aqueous solution (active polymer) has a vis-cosity of more than 22 centipoises at 22 °C (71.6 °F), as de-termined by LVF-series Brookfield viscometer using a No. 1 spindle at 60 r.p.m. (or by other equivalent method).For use only as a drainage and/or retention aid employed prior to the sheet-forming operation in the manufacture of paper and paperboard and limited to use at a level not to exceed 0.05 percent by weight of the finished paper and paper-board.Diallyldiethylammonium chloride polymer with acrylamide, and diallyldimethylammonium chloride, produced by copolym-erizing acrylamide, diallyldiethylammonium chloride, and diallyldimethylammonium chloride, respectively, in the fol-lowing weight ratios and having viscosities determined at 22 °C, by LVF-series Brookfield viscometer using a No. 1 spin-dle at 60 r.p.m. (or by other equivalent method), as follows:.1. Weight ratio: 50–2.5–47.5. The finished resin in a 1 per-cent by weight aqueous solution has a minimum vis-cosity of 22 centipoises.For use only as a retention aid employed prior to the sheet- forming operation in the manufacture of paper and paper-board and limited to use at a level not to exceed 0.05 per-cent by weight of the finished paper and paperboard.2. Weight ratio: 25–2.5–72.5. The finished resin in a 0.20 percent by weight aqueous solution has a minimum vis-cosity of 20 centipoises.For use only as a drainage and/or retention aid employed prior to the sheet-forming operation in the manufacture of paper and paperboard and limited to use at a level not to exceed 0.075 percent by weight of the finished paper and paper-board.3. Weight ratio: 80–2.5–17.5. The finished resin in a 0.30 percent by weight aqueous solution has a minimum vis-cosity of 50 centipoises.For use only as a drainage and/or retention aid employed prior to the sheet-forming operation in the manufacture of paper and paperboard and limited to use at a level not to exceed 0.075 percent by weight of the finished paper and paper-board.21 CFR Ch. I (4–1–05 Edition)§176.170List of SubstancesLimitationsDiallyldiethylammonium chloride polymer with acrylamide, po-tassium acrylate, and diallyldimethylammonium chloride. The polymer is produced by copolymerizing either: (1) acryl-amide, diallyldiethylammonium chloride, and diallyldimethylammonium chloride in a weight ratio of 50– 2.5–47.5, respectively, with 4.4 percent of the acrylamide subsequently hydrolyzed to potassium acrylate, or (2) acryl-amide, potassium acrylate (as acrylic acid),diallyldiethylammonium chloride, and diallyldimethylammonium chloride in a weight ratio of 47.8– 2.2–2.5–47.5, so that the finished resin in a 1 percent by weight aqueous solution has a minimum viscosity of 22 cen-tipoises at 22 °C, as determined by LVF-series Brookfield viscometer using a No. 1 spindle at 60 r.p.m. (or by other equivalent method).For use only as a retention aid employed prior to the sheet- forming operation in the manufacture of paper and paper-board and limited to use at a level not to exceed 0.05 per-cent by weight of the finished paper and paperboard. Diallyldimethylammonium chloride polymer with acrylamide, re-action product with glyoxal, produced by copolymerizing not less than 90 weight percent of acrylamide and not more than 10 weight percent of diallyldimethylammonium chloride, which is then cross-linked with not more than 30 weight per-cent of glyoxal, such that a 10 percent aqueous solution has a minimum viscosity of 25 centipoises at 25 °C as deter-mined by Brookfield viscometer Model RVF, using a No. 1 spindle at 100 r.p.m.For use only as a dry and wet strength agent employed prior to the sheet-forming operation in the manufacture of paper and paperboard in such an amount that the finished paper and paperboard will contain the additive at a level not in ex-cess of 2 percent by weight of the dry fibers in the finishedpaper and paperboard. 2,2-Dibromo-3-nitrilopropionamide (CAS Reg. No.10222–01–2). For use as a preservative at a level not to exceed 100 partsper million in coating formulations and in component slurries and emulsions, used in the production of paper and paper-board and coatings for paper and paperboard.2,5-Di-tert-butyl hydroquinone .....................................................For use only as an antioxidant for fatty based coating adju-vants provided it is used at a level not to exceed 0.005% by weight of coating solids.Diethanolamine ............................................................................For use only:1. As an adjuvant to control pulp absorbency and pitch content in the manufacture of paper and paperboard prior to the sheet-forming operation.2.In paper mill boilers.Diethanolamine salts of mono- and bis (1H ,1H ,2H ,2H -perfluo-roalkyl) phosphates where the alkyl group is even-numbered in the range C 8-C 18and the salts have a fluorine content of 52.4% to 54.4% as determined on a solids basis.For use only as an oil and water repellant at a level not to ex-ceed 0.17 pound (0.09 pound of fluorine) per 1,000 square feet of treated paper or paperboard, as determined by anal-ysis for total fluorine in the treated paper or paperboard with-out correction for any fluorine which might be present in theuntreated paper or paperboard, when such paper or paper-board is used in contact with nonalcoholic foods under the conditions of use described in paragraph (c) of this section, table 2, conditions of use (B) through (H).Diethyl(2-hydroxyethyl) methylammonium methyl sulfate, acry-late, polymer with acrylamide, chemical abstract service reg-istry No. [26796–75–8] having 90–95 mole pct. acrylamide, a nitrogen content of not more than 19.7 pct. (Kjeldahl, dry basis), and a residual acrylamide monomer content of not more than 0.1 pct. The finished polymer in a 1 pct. by weight aqueous solution has a minimum viscosity of 900 centipoises at 25 °C as determined by LVT-series Brookfield viscometer using a No. 2 spindle at 12 r.p.m. (or by equivalent method).For use only as a retention aid and drainage aid employed prior to the sheet-forming operation in the manufacture ofpaper and paperboard at a level not to exceed 0.15 pct. by weight of finished dry paper and paperboard fibers. Diethylenetriamine .......................................................................For use only as a modifier for amino resins.N,N-Diisopropanolamide of tallow fatty acids .............................For use only as an adjuvant to control pulp absorbency andpitch content in the manufacture of paper and paperboard prior to the sheet-forming operation.Dimethylamine-epichlorohydrin copolymer in which not more than 5 mole-percent of dimethylamine may be replaced by an equimolar amount of ethylenediamine and in which the ratio of total amine to epichlorohydrin does not exceed 1:1. The nitrogen content of the copolymer shall be 9.4 to 10.8 weight percent on a dry basis and a 10 percent by weight aqueous solution of the final product has a minimum vis-cosity of 5.0 centipoises at 25 °C, as determined by LVT-se-ries Brookfield viscometer using a No. 1 spindle at 60 r.p.m. (or by other equivalent method).For use only:1. As a retention aid employed before the sheet-forming oper-ation in the manufacture of paper and paperboard and lim-ited to use at a level not to exceed 1 percent by weight of the finished paper and paperboard.2. At the size press at a level not to exceed 0.017 percent by weight of the finished paper and paperboard.N-[(Dimethylamino)methyl]-acrylamide polymer with acrylamide and styrene having a nitrogen content of not more than 16.9 percent and a residual acrylamide monomer content of not more than 0.2 percent on a dry basis.For use only as a dry-strength agent employed prior to the sheet-forming operation in the manufacture of paper and pa-perboard and used at a level not to exceed 1 percent by weight of finished dry paper or paperboard fibers. N,N ′-Dioleoylethylenediamine.Food and Drug Administration, HHS §176.170 List of Substances Limitations Diphenylamine.............................................................................For use only as an antioxidant for fatty based coating adju-vants provided it is used at a level not to exceed 0.005% byweight of coating solids.Dipropylene glycol.Disodium salt of 1,4-dihydro-9,10-dihydroxyanthracene (CAS Reg. No. 73347–80–5).For use only as a catalyst in the alkaline pulping of lignocellulosic materials at levels not to exceed 0.1 percent by weight of the raw lignocellulosic materials.N,N′-Distearoylethylenediamine.n-Dodecylguanidine acetate........................................................For use only as an antimicrobial agent in paper and paper-board under the following conditions:1. For contact only with nonalcoholic food having a pH above 5and provided it is used at a level not to exceed 0.4 percentby weight of the paper and paperboard.2. For use in the outer ply of multiwall paper bags for contactwith dry food of Type VIII described in table I of paragraph(c) of this section and provided it is used at a level of 0.8percent by weight of the paper.n-Dodecylguanidine hydrochloride..............................................For use only as an antimicrobial agent in paper and paper-board under the following conditions:1. For contact only with nonalcoholic food having a pH above 5and provided it is used at a level not to exceed 0.4 percentby weight of the paper and paperboard.2. For use in the outer ply of multiwall paper bags for contactwith dry food of Type VIII described in table I of paragraph(c) of this section and provided it is used at a level of 0.8percent by weight of the paper.Fatty acids derived from animal and vegetable fats and oilsand salts of such acids, single or mixed, as follows:Aluminum.Ammonium.Calcium.Magnesium.Potassium.Sodium.Zinc.Ferric chloride.Ferrous ammonium sulfate.Fish oil, hydrogenated.Fish oil, hydrogenated, potassium salt.Furcelleran and salts of furcelleran as described in §§172.655and 172.660 of this chapter.Glutaraldehyde (CAS Reg. No. 111–30–8).................................For use only as an antimicrobial agent in pigment and fillerslurries used in the manufacture of paper and paperboard atlevels not to exceed 300 parts per million by weight of theslurry solids.Glyceryl lactostearate.Glyceryl mono-1,2-hydroxystearate.Glyceryl monoricinoleate.Guar gum modified by treatment with b-diethylamino- ethyl chloride hydrochloride.For use only as a retention aid and/or drainage aid employed prior to the sheet-forming operation in the manufacture of paper and paperboard.Guar gum modified by treatment with not more than 25 weight percent of 2,3-epoxypropyltri-methylammonium chloride such that the finished product has a maximum chlorine content of4.5 percent, a maximum nitrogen content of 3.0 percent, anda minimum viscosity in 1-percent-by-weight aqueous solution of 1,000 centipoises at 77 °F, as determined by RV-series Brookfield viscometer (or equivalent) using a No. 3 spindle at 20 r.p.m.For use only as a retention aid and/or internal size employed prior to the sheet-forming operation in the manufacture of paper and paperboard, and limited to use at a level: (1) Not to exceed 0.15 percent by weight of the finished dry paper and paperboard fibers intended for use in contact with all types of foods, except (2) not to exceed 0.30 pct. by weight of the finished dried paper and paperboard fibers for use with nonalcoholic and nonfatty food of types identified under Types I, II, IV-B, VI-B, VII-B, and VIII of table I in par. (c) of this section.N,N,N′,N′,N″,N″-Hexakis (methoxymethyl)-1,3,5-triazine-2,4,6- triamine polymer with stearyl alcohol, a-octadecenyl-omega- hydroxypoly(oxy-1,2-ethanediyl), and alkyl (C20+) alcohols (CAS Reg. No. 130328–24–4).For use only as a water-repellent applied to the surface of paper and paperboard at levels not to exceed 1 percent by weight of the finished dry paperboard fibers. The finished paper and paperboard will be used in contact with aqueous foods under conditions of use B through G as described in table 2 of paragraph (c) of this section.Hexamethylenetetramine.............................................................For use only as polymerization cross-linking agent for protein,including casein.Hydroquinone and the monomethyl or monoethyl ethers of hy-droquinone.For use only as an inhibitor for monomers.。

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=====================================================================Acq. Operator : Li Shan(LCMS-02) Seq. Line : 85
Acq. Instrument : HY-LCMS-02 Location : Vial 73Injection Date : 12/22/2014 4:51:22 PM Inj : 1
Inj Volume : 3.000 µl
Acq. Method : D:\AGLIENT 1260\DATA\20141222\20141222 2014-12-22 09-20-15\100-1000MS+3MIN( 0.02%FA).M
Last changed : 12/22/2014 9:20:15 AM by Li Shan(LCMS-02)Analysis Method : D:\AGLIENT 1260\METHOD\HM-046_6-H01P.M Last changed : 12/22/2014 5:30:45 PM by Li Shan(LCMS-02) (modified after loading) M ethod Info : HPLC
Catalog No : HY-10367A Batch#04044 A-RP-32
Additional Info : Peak(s) manually integrated
min
0.5
1
1.5
2 2.53mAU 0
100200300400500600700 DAD1 C, Sig=254,4 Ref=off (D:\AGLIENT...0\DATA\20141222\20141222 2014-12-22 09-20-15\CPK2014-D22-04044.D)
1.353
1.966
===================================================================== Area Percent Report =====================================================================
Sorted By : Signal Multiplier : 1.0000Dilution : 1.0000
Do not use Multiplier & Dilution Factor with ISTDs
Signal 1: DAD1 C, Sig=254,4 Ref=off
Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] %
----|-------|----|-------|----------|----------|--------| 1 1.353 MM R 0.0782 3745.05786 795.02191 99.8577 2 1.966 MM R 0.0788 5.33771 1.12826 0.1423
Totals : 3750.39557 796.15017
===================================================================== *** End of Report ***
=====================================================================Acq. Operator : Li Shan(LCMS-02) Seq. Line : 85
Acq. Instrument : HY-LCMS-02 Location : Vial 73Injection Date : 12/22/2014 4:51:22 PM Inj : 1
Inj Volume : 3.000 µl
Acq. Method : D:\AGLIENT 1260\DATA\20141222\20141222 2014-12-22 09-20-15\100-1000MS+3MIN( 0.02%FA).M
Last changed : 12/22/2014 9:20:15 AM by Li Shan(LCMS-02)Analysis Method : D:\AGLIENT 1260\METHOD\HM-046_6-H01P.M Last changed : 12/22/2014 5:32:32 PM by Li Shan(LCMS-02) (modified after loading) M ethod Info : HPLC
Catalog No : HY-10367A Batch#04044 A-RP-32
Additional Info : Peak(s) manually integrated
min
0.5
1
1.5
2
2.5
3
200000
40000060000080000010000001200000 MSD1 TIC, MS File (D:\AGLIENT 1260\DATA\20141222\20141222 2014-12-22 09-20-15\CPK2014-D22-04044.D) ES-API, Pos, S
1.362
MS Signal: MSD1 TIC, MS File, ES-API, Pos, Scan, Frag: 50 Spectra averaged over upper half of peaks. Noise Cutoff: 1000 counts.
Reportable Ion Abundance: > 10%.
Retention Mol. Weight Time (MS) MS Area or Ion
1.362 12232840 488.10 I 486.10 I 244.40 I 243.60 I
m/z
100
200
3004005006007008000
204060
80100*MSD1 SPC, time=1.325:1.434 of D:\AGLIENT 1260\DATA\20141222\20141222 2014-12-22 09-20-15\CPK2014-D22-04044.D ES-API Max: 499346
487.1 486.1
244.4 243.6
*** End of Report ***。