CN111195348A - 一种生长抑素纳米混悬剂及其制备方法 - Google Patents
一种生长抑素纳米混悬剂及其制备方法 Download PDFInfo
- Publication number
- CN111195348A CN111195348A CN201811374045.XA CN201811374045A CN111195348A CN 111195348 A CN111195348 A CN 111195348A CN 201811374045 A CN201811374045 A CN 201811374045A CN 111195348 A CN111195348 A CN 111195348A
- Authority
- CN
- China
- Prior art keywords
- somatostatin
- surfactant
- nanosuspension
- injection
- suspension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000005157 Somatostatin Human genes 0.000 title claims abstract description 52
- 108010056088 Somatostatin Proteins 0.000 title claims abstract description 52
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 title claims abstract description 52
- 229960000553 somatostatin Drugs 0.000 title claims abstract description 52
- 239000006070 nanosuspension Substances 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 18
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000000725 suspension Substances 0.000 claims description 30
- 239000004094 surface-active agent Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000008215 water for injection Substances 0.000 claims description 14
- 239000007853 buffer solution Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 8
- -1 sorbitan fatty acid Chemical class 0.000 claims description 8
- 239000003945 anionic surfactant Substances 0.000 claims description 6
- 239000002736 nonionic surfactant Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000005538 encapsulation Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000010008 shearing Methods 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 claims description 4
- GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 239000003093 cationic surfactant Substances 0.000 claims description 2
- 150000002191 fatty alcohols Chemical class 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 229940077386 sodium benzenesulfonate Drugs 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- MZSDGDXXBZSFTG-UHFFFAOYSA-M sodium;benzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=CC=C1 MZSDGDXXBZSFTG-UHFFFAOYSA-M 0.000 claims description 2
- 229940080236 sodium cetyl sulfate Drugs 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000004090 dissolution Methods 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 210000005070 sphincter Anatomy 0.000 description 2
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000001380 Diabetic Ketoacidosis Diseases 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- 235000001418 Echinochloa stagnina Nutrition 0.000 description 1
- 240000001327 Echinochloa stagnina Species 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 102100021022 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 206010017865 Gastritis erosive Diseases 0.000 description 1
- 206010017866 Gastritis haemorrhagic Diseases 0.000 description 1
- 206010017886 Gastroduodenal ulcer Diseases 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003442 median eminence Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 208000024691 pancreas disease Diseases 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明属于药物制剂领域，具体涉及到一种生长抑素纳米混悬剂，能够显著提高药物溶出度和生物利用度，且无须载体，使得给药体积减小，毒性降低，提高了患者的顺应性，易于实现工业化生产。
Description
技术领域
本发明属于药物制剂领域，具体涉及到一种生长抑素纳米混悬剂其制备方法。
技术背景
生长抑素是下丘脑的正中隆起和胰岛的δ细胞合成的。1973年由Burgus和Brazean等人首先由下丘脑分离得到并阐明其结构。化学结构为分子内带有一对二硫键的十四肽。其生物功能可抑制腺体释放生长激素、抑制促甲状腺和肾上腺皮质激素、抑制胰腺的内分泌与外分泌、抑制胃粘膜释放胃泌素、抑制肠粘膜释放肠促胰激素和肾脏释放肾素，降低门静脉压力、松弛胆道口括约肌、刺激单核巨噬细胞系统而减轻内毒素血症，抑制血小板活化因子的释放，直接或间接调节细胞因子链产生细胞保护作用，并可增强抗癌药物的抗增殖作用。临床常应用于严重急性食管静脉曲张破裂出血，严重急性胃、十二指肠溃疡出血，急性糜烂性胃炎或出血性胃炎，胰、胆和肠屡的辅助治疗，糖尿病酮症酸中毒的辅助治疗。
其临床用法一般为生长抑素250μg静脉注射，然后以每小时25μg的速度静脉滴注。待确认出血停止后，再继续使用24-48小时即可停药。但由于生长抑素难溶于水，半衰期极短，给静脉用药带来很大困难，患者依从性差。现有生长抑素一般以冻干粉针的形式用于临床，但现有的冷冻干燥技术对生长抑素分子的活性有破坏作用，容易引起生长抑素药物变性；且冻干制剂生产工艺难度较大，且成本较高，产品颜色及成型均较差。
中国专利CN100336557C公开了一种含有抗氧化剂乙二胺四乙酸二钠等辅料的生长抑素水溶液制剂。由于乙二胺四乙酸二钠可与钙离子结合成可溶的络合物引起钙的减少，静脉制剂中使用依地酸二钠会导致血钙下降，因此，在注射液中使用乙二胺四乙酸二钠的安全性无法得到确切保证，需密切关注和严格控制静脉给药制剂中依地酸二钠的用量。
中国专利CN1559396A和中国专利CN1415378A在制备过程中均采用了低温干燥技术，该项技术对生长抑素分子的活性有破坏作用，容易引起生长抑素药物变性；且冻干制剂生产工艺难度较大，且成本较高，产品颜色及成型均较差。
为了解决上述问题，本申请提供了一种生长抑素纳米混悬剂，不仅显著提高药物溶出度和生物利用度，且无须载体，使得给药体积减小，毒性降低，提高了患者的顺应性，易于实现工业化生产。
发明内容
本发明的目的在于：提供一种生长抑素纳米混悬剂及其制备方法。
本发明提供一种如下所述的生长抑素纳米混悬剂：
一种生长抑素纳米混悬剂，包括：
生长抑素1-2000mg
表面活性剂20-40000mg
注射用水加至500ml。
进一步地，一种生长抑素纳米混悬剂，包括：
生长抑素1-1500mg
表面活性剂20-30000mg
等渗调节剂0-10％
缓冲液0-30mmol/l
注射用水加至500ml
进一步地，一种生长抑素纳米混悬剂，包括：
生长抑素100-1500mg
表面活性剂5-30000mg
等渗调节剂0-10％
缓冲液0-30mmol/l
注射用水加至500ml；
进一步地，本发明所述表面活性剂选自阴离子表面活性剂、阳离子表面活性剂、非离子表面活性剂中的一种或几种；
进一步地，本发明所述表面活性剂选自阴离子表面活性剂、非离子表面活性剂中的一种或几种；
进一步地，本发明所述阴离子表面活性剂选自硫酸化蓖麻油、月桂醇硫酸钠、十六烷基硫酸钠、苯磺酸钠、琥珀酸二钠中的一种或几种；
进一步地，本发明所述非离子表面活性剂选自脂肪酸甘油酯、脂肪酸山梨坦、聚山梨酯、聚氧乙烯脂肪酸酯、聚氧乙烯脂肪醇醚中的一种或几种；
本发明还提供一种生长抑素纳米混悬剂的制备方法：
(1)取表面活性剂、等渗调节剂和缓冲液溶解于注射用水中，再加入生长抑素原料药混合，得生长抑素混悬液；
(2)将步骤(1)所得混悬液高速剪切1-3分钟，得初悬液；
(3)将步骤(2)所得初悬液经高压均质机循环处理，压力为2700psi，得到混悬液；
(4)将步骤(3)所得混悬液经过滤除菌后，进行无菌灌封，即得生长抑素纳米混悬浓缩液。
有益效果：
本发明提高了生长抑素的生物利用度、延长了其半衰期，从而提高了其治疗效果和患者依从性，并且降低药物的毒性作用。本发明制备过程中不加入有机溶剂且无须干燥冷冻，选择适当的表面活性剂组合及浓度，在适当的压力下循环数次即可形成生长抑素纳米混悬剂，生产工艺简单，便于工业化生产。
具体实施方式
实施例1
| 成分 | 含量 |
| 生长抑素 | 1500 |
| 琥珀酸二钠 | 3000 |
| 吐温80 | 1000 |
| 注射用水(ml) | 500 |
制备方法：
(1)取表面活性剂、等渗调节剂和缓冲液溶解于注射用水中，再加入生长抑素原料药混合，得生长抑素混悬液；
(2)将步骤(1)所得混悬液高速剪切1-3分钟，得初悬液；
(3)将步骤(2)所得初悬液经高压均质机循环处理，压力为2700psi，得到混悬液；
(4)将步骤(3)所得混悬液经过滤除菌后，进行无菌灌封。
实施例2
| 成分 | 含量 |
| 生长抑素 | 250 |
| 琥珀酸二钠 | 600 |
| 吐温80 | 200 |
| 甘露醇 | 20 |
| 磷酸盐缓冲液(mmol/l) | 20 |
| 注射用水(ml) | 500 |
制备方法：
(1)取表面活性剂、等渗调节剂和缓冲液溶解于注射用水中，再加入生长抑素原料药混合，得生长抑素混悬液；
(2)将步骤(1)所得混悬液高速剪切1-3分钟，得初悬液；
(3)将步骤(2)所得初悬液经高压均质机循环处理，压力为2700psi，得到混悬液；
(4)将步骤(3)所得混悬液经过滤除菌后，进行无菌灌封。
实施例3
| 成分 | 含量 |
| 生长抑素 | 375 |
| 十六烷基硫酸钠 | 1182 |
| 吐温80 | 393 |
| 等渗调节剂 | 20 |
| 磷酸盐缓冲液(mmol/l) | 20 |
| 注射用水(ml) | 500 |
制备方法：
(1)取表面活性剂、等渗调节剂和缓冲液溶解于注射用水中，再加入生长抑素原料药混合，得生长抑素混悬液；
(2)将步骤(1)所得混悬液高速剪切1-3分钟，得初悬液；
(3)将步骤(2)所得初悬液经高压均质机循环处理，压力为2700psi，得到混悬液；
(4)将步骤(3)所得混悬液经过滤除菌后，进行无菌灌封。
采用上述制备方法，对制得的生长抑素纳米混悬注射液进行质量检测，其结果见表1
表1
Claims (8)
1.一种生长抑素纳米混悬剂，其特征在于：包括
生长抑素1-2000mg
表面活性剂20-40000mg
等渗调节剂0-10％
缓冲液0-30mmol/l
注射用水加至500ml。
2.根据权利要求1所述的生长抑素纳米混悬剂，其特征在于：包括
生长抑素1-1500mg
表面活性剂20-30000mg
等渗调节剂0-10％
缓冲液0-30mmol/l
注射用水加至500ml。
3.根据权利要求1所述的生长抑素纳米混悬剂，其特征在于：包括
生长抑素100-1500mg
表面活性剂5-30000mg
等渗调节剂0-10％
缓冲液0-30mmol/l
注射用水加至500ml。
4.根据权利要求1-3所述的生长抑素纳米混悬剂，其特征在于：所述表面活性剂选自阴离子表面活性剂、阳离子表面活性剂、非离子表面活性剂中的一种或几种。
5.根据权利要求4所述的生长抑素纳米混悬剂，其特征在于：所述表面活性剂选自阴离子表面活性剂、非离子表面活性剂中的一种或几种。
6.根据权利要求5所述的生长抑素纳米混悬剂，其特征在于：所述阴离子表面活性剂选自硫酸化蓖麻油、月桂醇硫酸钠、十六烷基硫酸钠、苯磺酸钠、琥珀酸二钠中的一种或几种。
7.根据权利要求5所述的生长抑素纳米混悬剂，其特征在于：所述非离子表面活性剂选自脂肪酸甘油酯、脂肪酸山梨坦、聚山梨酯、聚氧乙烯脂肪酸酯、聚氧乙烯脂肪醇醚中的一种或几种。
8.一种生长抑素纳米混悬剂的制备方法：
(1)取表面活性剂、等渗调节剂和缓冲液溶解于注射用水中，再加入生长抑素原料药混合，得生长抑素混悬液；
(2)将步骤(1)所得混悬液高速剪切1-3分钟，得初悬液；
(3)将步骤(2)所得初悬液经高压均质机循环处理，压力为2700psi，得到混悬液；
(4)将步骤(3)所得混悬液经过滤除菌后，进行无菌灌封。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811374045.XA CN111195348A (zh) | 2018-11-19 | 2018-11-19 | 一种生长抑素纳米混悬剂及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811374045.XA CN111195348A (zh) | 2018-11-19 | 2018-11-19 | 一种生长抑素纳米混悬剂及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111195348A true CN111195348A (zh) | 2020-05-26 |
Family
ID=70741236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811374045.XA Pending CN111195348A (zh) | 2018-11-19 | 2018-11-19 | 一种生长抑素纳米混悬剂及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111195348A (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050112188A1 (en) * | 2003-11-17 | 2005-05-26 | Eliaz Rom E. | Composition and dosage form comprising an amphiphilic molecule as a suspension vehicle |
| CN1638732A (zh) * | 2002-03-04 | 2005-07-13 | 研究及应用科学协会股份有限公司 | 含载体肽的缓释药物制剂 |
| US20090202596A1 (en) * | 2006-06-13 | 2009-08-13 | Farmatron Limited | Pharmaceutical compositions with biological barriers permeation enhancing properties |
-
2018
- 2018-11-19 CN CN201811374045.XA patent/CN111195348A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1638732A (zh) * | 2002-03-04 | 2005-07-13 | 研究及应用科学协会股份有限公司 | 含载体肽的缓释药物制剂 |
| US20050112188A1 (en) * | 2003-11-17 | 2005-05-26 | Eliaz Rom E. | Composition and dosage form comprising an amphiphilic molecule as a suspension vehicle |
| US20090202596A1 (en) * | 2006-06-13 | 2009-08-13 | Farmatron Limited | Pharmaceutical compositions with biological barriers permeation enhancing properties |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101089049B1 (ko) | 친지성 약물의 제형 | |
| KR102465046B1 (ko) | 5-콜레스텐-3, 25-디올, 3-술페이트 (25hc3s) 또는 이의 약학적으로 허용 가능한 염, 및 적어도 하나의 시클릭 올리고당을 포함하는 조성물 | |
| CN101366696B (zh) | 一种紫杉醇的水溶性注射用药物组合物、制备方法及用途 | |
| CN102068453B (zh) | 一种稳定的复合维生素组合物及其制备方法 | |
| CN100506208C (zh) | 蟾酥纳米脂质体及其制备方法 | |
| CN111407721B (zh) | 一种促进活性成分渗透皮肤的体系 | |
| CN101322690A (zh) | 一种稳定的药物脂质复合物 | |
| CN110870868A (zh) | 包含亚甲蓝类染料、营养素或/和抗肿瘤化合物的药物组合物及其应用 | |
| CN101513387A (zh) | 埃索美拉唑镁注射液 | |
| CN101700229B (zh) | 静脉注射用前列地尔长循环脂微球制剂及其制备方法 | |
| CN1056746C (zh) | 含有效成分的冻干乳液 | |
| Faraj et al. | Mechanism of nasal absorption of drugs. III: nasal absorption of leucine enkephalin | |
| EP2813215B1 (en) | 2,2',6,6'-tetraisopropyl-4,4'-2-biphenol lipid microsphere preparation and preparation method therefor | |
| KR20140091652A (ko) | 안정적이며 바로 사용 가능한 세트로레릭스 주사액 | |
| CN111195348A (zh) | 一种生长抑素纳米混悬剂及其制备方法 | |
| CN101439019A (zh) | 一种紫杉醇纳米脂质载体及其制备方法 | |
| CN101028250A (zh) | 藤黄酸脂质体及其冻干粉针剂与制备方法 | |
| JPS58189118A (ja) | 経鼻投与製剤 | |
| JPS60149530A (ja) | 水性製剤 | |
| CZ2005796A3 (cs) | Farmaceutická kompozice obsahující derivát taxanuse zlepsenou terapeutickou úcinností | |
| CN101491495B (zh) | 丹酚酸b镁注射剂、制备方法及应用 | |
| CN101444479A (zh) | 一种拉帕替尼注射液及其制备方法 | |
| CN114366715A (zh) | 雷帕霉素自微乳注射剂及其制备方法及其应用 | |
| CN111465389B (zh) | 多西他赛共缀物的药物组合物及制备方法 | |
| CN102552923A (zh) | 包含左卡尼汀和辅酶q10的药物组合物及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |