Alfaxalone 简介
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
CHARACTERISTICS A white to creamy white powder. Practically insoluble in water; freely soluble in chloroform; soluble in ethanol (96%); practically insoluble in petroleum spirit (boiling range, 60°to 80°).
原料药开发
1. 查阅工艺文献资料 2. 查阅检测文献资料（药典） 3. 根据工艺文献资料，列出不同工艺的优缺点，提出拟实施实验室工艺路线 4. 提出工艺研究方案包括步骤、反应条件、参数、规模等操作规程 5. 提出原料药分析检测（含量及有关物质）的方案 6. 提出实验室工艺和分析研究的预算 7. 根据小试实验操作规程，开始第1次实验室工艺研究，目标是合成1g 8. 建立起始原料检测方法（参考厂家提供的方法） 9. 建立中间体检测方法 10.建立终产品含量检测方法（参考USP、EP、BP、CP等标准） 11.建立有关物质分析检测方法（参考USP、EP、BP、CP等标准） 12.分析检测每一步实验样品，指导合成实验 13.汇报分析检验结果并完善和优化（PPT汇报） 14.全面检验第1次小试的中间体、终产品包括紫外、红外、核磁等
Alfaxan 兽药（国外）
10ml包装
20ml包装
Alfaxalone (alphaxalone) - brand name Alfaxan
Steroid with anesthetic properties (but no steroid effects)
Beneficial qualities:
Dose recommendations:
·2 mg/kg IM for chemical restraint or anesthetic premedication. ·1 to 3 mg/kg IV for induction of anesthesia.
J Parenter Sci Technol. 1989 Nov-Dec;43(6):262-5. Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins. Brewster ME, Estes KS, Bodor N. Abstract
英国药典（2014）
IDENTIFICATION A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of alfaxalone (RSV 03). 红外吸收光谱 B. Complies with the test for identification of steroids, Appendix III A, using impregnating solvent II and mobile phase D. C. In the Assay, the chromatogram obtained with solution (2) shows a peak having the same retention time as the peak due to alfaxalone BPCRS in the chromatogram obtained with solution (1).
Ordering Information
Welcome to Santa Cruz Biotechnology!
Product Name CatalLeabharlann Baidug #
Unit
Price
Alphaxalone sc-203814 10 mg $115
Alphaxalone sc-203814A 50 mg $473
英国药典（2014）
TESTS Light absorption Absorbance of a 0.20% w/v solution in ethanol (96%) at 235 nm, not more than 0.20, calculated with reference to the dried substance, Appendix II B. Related substances Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of equal volumes of ethyl acetate andtoluene as the mobile phase. Apply separately to the plate 10 µL of each of three solutions of the substance being examined in a mixture of equal volumes of chloroformand methanol containing (1) 5.0% w/v, (2) 0.15% w/v and (3) 0.050% w/v. After removal of the plate, dry it in a current of air until the solvent has evaporated, spray with a saturated solution of cerium (IV) sulfate in sulfuric acid (50%) and heat at 110°for 1 hour. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (3%) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3) (1%).
3
5
Systematic (IUPAC) name
3α-hydroxy-5α-pregnane-11,20-dione
CAS
23930-19-0
Formula
C21H32O3
Molecular mass 332.477 g/mol
阿法沙龙基本信息
• 为新型固醇类麻醉药，用于全麻的诱导、短小手术及外科处置，或 作为其他全麻的辅助药。不适用于有强烈疼痛手术的麻醉
Indications:
·Induction of anesthesia.(麻醉诱导) ·Chemical restraint/sedation for non painful manipulations such as diagnostic imaging, IV catheter placement. ·(非疼痛性操作的化学抑制/镇静，如诊断成像，静脉导管放置)。
P5052-10MG 需要从国外调货 sigma订购
1,886.04
Technical Information
Physical State: Solid
Solubility:
Soluble in DMSO (100 mM), ethanol (100 mM), and chloroform (50 mg/ml).
Storage:
Store at room temperature
Melting Point: 172-174 °C
Boiling Point: Density:
~468.1 °C at 760 mmHg (Predicted) ~1.1 g/cm3 (Predicted)
Refractive Index:
The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.
英国药典（2014）
DEFINITION Alfaxalone is 3α-hydroxy-5α-pregnane-11, 20-dione. It contains not less than 95.0% and not more than 103.0% of C21H32O3, calculated with reference to the dried substance.
英国药典（2014）
•British Pharmacopoeia (Veterinary) •Monographs •Medicinal and Pharmaceutical Substances
General Notices
Alfaxalone
C21H32O3 332.5 23930-19-0 Action and use Intravenous general anaesthetic.
• 目前在国内外均没有上市人用药 • 在澳大利亚有动物药上市销售，Alfaxan 1x10ml ；£29.40 • 化学试剂10mg可以在sigma订购，10mg，1886元。 • 国内网站可以查到相关阿法沙龙原料供货商信息，经调研，均没有
生产，也没有货。武汉易泰科技有限公司上海分公司销售国外试剂， 价格比sigma还贵
n20D 1.53 (Predicted)
Optical Activity:
α25/D 112.5º±2.5º, c = 1.2 in chloroform; α20/D 109.7º, c = 1.2 in chloroform
IC50:
GABA-A receptor; anion channel: IC50 = 0.3 µM (rat); GABAA receptor α1β1γ3: EC5050 = 1.4 µM; GABAA receptor α1β1γ1: EC5050 = 1.8 µM; GABA A receptor α-2/β2/γ-2: EC5050 = 2 µM (human); GABAA receptor β1γ1: EC5050 = 2.1 µM
1类静脉麻醉药阿法沙龙的开发
立项：
老药：70年代至80年代由GSK开发上市，因为辅料蓖麻油不纯导致的过 敏副作用而退市。
按1类新药开发：国内外均未上市，澳大利亚正在进行临床前研究，估计 尽快会开展临床研究
原料药生产：与陕西汉江制药合作
专利：化合物没有专利，制剂专利在中国申请保护
制剂：环糊精为辅料，国内有合法来源
同类产品“丙泊酚”每年销售额为10亿人民币，外国进口和国产药市场 份额相当；丙泊酚原料药价格约1500元；制剂0.1g/10ml；17.5元人民币； 原料药成本约0.15元。
兽药：目前澳大利亚、欧洲、美国有阿法沙龙的兽药上市销售。在开发 人用药的同时，可以考虑开发兽药
阿法沙龙基本信息
20
11
·Minimal hypotension.（很少发生低血压） ·Minimal changes in heart rate.（很少发生心率改变） ·Minimal respiratory depression.（很少发生呼吸抑制） ·No tissue irritation if administered peri vascularly.（外周血管使用无组织刺激） ·Suitable as an intramuscular sedative.（可用于肌肉注射镇静） ·Excellent muscle relaxation providing ease of endotracheal intubation. （提供方便的气管插管的良 好肌肉放松）
Undesirable characteristics:
·Calculated volume may be impractical for sedation of larger patients (dogs).针对大动物（狗）的镇 静，计算量需要注意 ·No preservative - contents of opened bottle should be discarded after initial use.
原料药开发
1. 查阅工艺文献资料 2. 查阅检测文献资料（药典） 3. 根据工艺文献资料，列出不同工艺的优缺点，提出拟实施实验室工艺路线 4. 提出工艺研究方案包括步骤、反应条件、参数、规模等操作规程 5. 提出原料药分析检测（含量及有关物质）的方案 6. 提出实验室工艺和分析研究的预算 7. 根据小试实验操作规程，开始第1次实验室工艺研究，目标是合成1g 8. 建立起始原料检测方法（参考厂家提供的方法） 9. 建立中间体检测方法 10.建立终产品含量检测方法（参考USP、EP、BP、CP等标准） 11.建立有关物质分析检测方法（参考USP、EP、BP、CP等标准） 12.分析检测每一步实验样品，指导合成实验 13.汇报分析检验结果并完善和优化（PPT汇报） 14.全面检验第1次小试的中间体、终产品包括紫外、红外、核磁等
Alfaxan 兽药（国外）
10ml包装
20ml包装
Alfaxalone (alphaxalone) - brand name Alfaxan
Steroid with anesthetic properties (but no steroid effects)
Beneficial qualities:
Dose recommendations:
·2 mg/kg IM for chemical restraint or anesthetic premedication. ·1 to 3 mg/kg IV for induction of anesthesia.
J Parenter Sci Technol. 1989 Nov-Dec;43(6):262-5. Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins. Brewster ME, Estes KS, Bodor N. Abstract
英国药典（2014）
IDENTIFICATION A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of alfaxalone (RSV 03). 红外吸收光谱 B. Complies with the test for identification of steroids, Appendix III A, using impregnating solvent II and mobile phase D. C. In the Assay, the chromatogram obtained with solution (2) shows a peak having the same retention time as the peak due to alfaxalone BPCRS in the chromatogram obtained with solution (1).
Ordering Information
Welcome to Santa Cruz Biotechnology!
Product Name CatalLeabharlann Baidug #
Unit
Price
Alphaxalone sc-203814 10 mg $115
Alphaxalone sc-203814A 50 mg $473
英国药典（2014）
TESTS Light absorption Absorbance of a 0.20% w/v solution in ethanol (96%) at 235 nm, not more than 0.20, calculated with reference to the dried substance, Appendix II B. Related substances Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of equal volumes of ethyl acetate andtoluene as the mobile phase. Apply separately to the plate 10 µL of each of three solutions of the substance being examined in a mixture of equal volumes of chloroformand methanol containing (1) 5.0% w/v, (2) 0.15% w/v and (3) 0.050% w/v. After removal of the plate, dry it in a current of air until the solvent has evaporated, spray with a saturated solution of cerium (IV) sulfate in sulfuric acid (50%) and heat at 110°for 1 hour. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (3%) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3) (1%).
3
5
Systematic (IUPAC) name
3α-hydroxy-5α-pregnane-11,20-dione
CAS
23930-19-0
Formula
C21H32O3
Molecular mass 332.477 g/mol
阿法沙龙基本信息
• 为新型固醇类麻醉药，用于全麻的诱导、短小手术及外科处置，或 作为其他全麻的辅助药。不适用于有强烈疼痛手术的麻醉
Indications:
·Induction of anesthesia.(麻醉诱导) ·Chemical restraint/sedation for non painful manipulations such as diagnostic imaging, IV catheter placement. ·(非疼痛性操作的化学抑制/镇静，如诊断成像，静脉导管放置)。
P5052-10MG 需要从国外调货 sigma订购
1,886.04
Technical Information
Physical State: Solid
Solubility:
Soluble in DMSO (100 mM), ethanol (100 mM), and chloroform (50 mg/ml).
Storage:
Store at room temperature
Melting Point: 172-174 °C
Boiling Point: Density:
~468.1 °C at 760 mmHg (Predicted) ~1.1 g/cm3 (Predicted)
Refractive Index:
The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.
英国药典（2014）
DEFINITION Alfaxalone is 3α-hydroxy-5α-pregnane-11, 20-dione. It contains not less than 95.0% and not more than 103.0% of C21H32O3, calculated with reference to the dried substance.
英国药典（2014）
•British Pharmacopoeia (Veterinary) •Monographs •Medicinal and Pharmaceutical Substances
General Notices
Alfaxalone
C21H32O3 332.5 23930-19-0 Action and use Intravenous general anaesthetic.
• 目前在国内外均没有上市人用药 • 在澳大利亚有动物药上市销售，Alfaxan 1x10ml ；£29.40 • 化学试剂10mg可以在sigma订购，10mg，1886元。 • 国内网站可以查到相关阿法沙龙原料供货商信息，经调研，均没有
生产，也没有货。武汉易泰科技有限公司上海分公司销售国外试剂， 价格比sigma还贵
n20D 1.53 (Predicted)
Optical Activity:
α25/D 112.5º±2.5º, c = 1.2 in chloroform; α20/D 109.7º, c = 1.2 in chloroform
IC50:
GABA-A receptor; anion channel: IC50 = 0.3 µM (rat); GABAA receptor α1β1γ3: EC5050 = 1.4 µM; GABAA receptor α1β1γ1: EC5050 = 1.8 µM; GABA A receptor α-2/β2/γ-2: EC5050 = 2 µM (human); GABAA receptor β1γ1: EC5050 = 2.1 µM
1类静脉麻醉药阿法沙龙的开发
立项：
老药：70年代至80年代由GSK开发上市，因为辅料蓖麻油不纯导致的过 敏副作用而退市。
按1类新药开发：国内外均未上市，澳大利亚正在进行临床前研究，估计 尽快会开展临床研究
原料药生产：与陕西汉江制药合作
专利：化合物没有专利，制剂专利在中国申请保护
制剂：环糊精为辅料，国内有合法来源
同类产品“丙泊酚”每年销售额为10亿人民币，外国进口和国产药市场 份额相当；丙泊酚原料药价格约1500元；制剂0.1g/10ml；17.5元人民币； 原料药成本约0.15元。
兽药：目前澳大利亚、欧洲、美国有阿法沙龙的兽药上市销售。在开发 人用药的同时，可以考虑开发兽药
阿法沙龙基本信息
20
11
·Minimal hypotension.（很少发生低血压） ·Minimal changes in heart rate.（很少发生心率改变） ·Minimal respiratory depression.（很少发生呼吸抑制） ·No tissue irritation if administered peri vascularly.（外周血管使用无组织刺激） ·Suitable as an intramuscular sedative.（可用于肌肉注射镇静） ·Excellent muscle relaxation providing ease of endotracheal intubation. （提供方便的气管插管的良 好肌肉放松）
Undesirable characteristics:
·Calculated volume may be impractical for sedation of larger patients (dogs).针对大动物（狗）的镇 静，计算量需要注意 ·No preservative - contents of opened bottle should be discarded after initial use.