CN114601792A - 一种甲钴胺注射液的制备方法 - Google Patents
一种甲钴胺注射液的制备方法 Download PDFInfo
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- CN114601792A CN114601792A CN202111175737.3A CN202111175737A CN114601792A CN 114601792 A CN114601792 A CN 114601792A CN 202111175737 A CN202111175737 A CN 202111175737A CN 114601792 A CN114601792 A CN 114601792A
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- Prior art keywords
- mecobalamin
- injection
- preparation
- water
- filling
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- 229960005321 mecobalamin Drugs 0.000 title claims abstract description 97
- 235000007672 methylcobalamin Nutrition 0.000 title claims abstract description 97
- 239000011585 methylcobalamin Substances 0.000 title claims abstract description 97
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 title claims abstract description 97
- 238000002347 injection Methods 0.000 title claims abstract description 65
- 239000007924 injection Substances 0.000 title claims abstract description 65
- 238000002360 preparation method Methods 0.000 title claims abstract description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000007788 liquid Substances 0.000 claims abstract description 28
- 239000000243 solution Substances 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 23
- 239000008215 water for injection Substances 0.000 claims abstract description 23
- 238000011049 filling Methods 0.000 claims abstract description 22
- 230000001954 sterilising effect Effects 0.000 claims abstract description 22
- 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 claims abstract description 19
- 229930195725 Mannitol Natural products 0.000 claims abstract description 19
- 235000010355 mannitol Nutrition 0.000 claims abstract description 19
- 239000000594 mannitol Substances 0.000 claims abstract description 19
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 17
- 238000001914 filtration Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000004695 Polyether sulfone Substances 0.000 claims abstract description 8
- 239000012528 membrane Substances 0.000 claims abstract description 8
- 229920006393 polyether sulfone Polymers 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 238000004090 dissolution Methods 0.000 claims abstract description 6
- 230000003204 osmotic effect Effects 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 29
- 239000012535 impurity Substances 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- DQOCFCZRZOAIBN-WZHZPDAFSA-L hydroxycobalamin Chemical compound O.[Co+2].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O DQOCFCZRZOAIBN-WZHZPDAFSA-L 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000015556 catabolic process Effects 0.000 abstract description 14
- 238000006731 degradation reaction Methods 0.000 abstract description 14
- 238000011056 performance test Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229930003779 Vitamin B12 Natural products 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 235000019163 vitamin B12 Nutrition 0.000 description 2
- 239000011715 vitamin B12 Substances 0.000 description 2
- 102000011848 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Human genes 0.000 description 1
- 108010075604 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Proteins 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000013441 quality evaluation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
名称 | 用途 | 单位剂量(mg) |
甲钴胺 | 活性成分 | 0.5 |
甘露醇 | 渗透压调节剂 | 50 |
注射用水 | 溶剂 | 至1ml |
样品 | 实施例2-1 | 实施例2-2 | 实施例2-3 | 参比 |
性状 | 红色澄明液体 | 红色澄明液体 | 红色澄明液体 | 红色澄明液体 |
pH值 | 6.050 | 6.304 | 6.367 | 5.3~7.3 |
羟钴胺/% | 0.057 | 0.148 | 0.095 | ≤2.0 |
最大未知单杂/% | 0.168 | 0.254 | 0.242 | ≤0.5 |
总杂/% | 0.396 | 0.716 | 0.496 | ≤2.5 |
含量(100%) | 98.6 | 98.4 | 101.3 | 90-110 |
Claims (9)
Priority Applications (1)
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CN202111175737.3A CN114601792B (zh) | 2021-10-09 | 2021-10-09 | 一种甲钴胺注射液的制备方法 |
Applications Claiming Priority (1)
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CN202111175737.3A CN114601792B (zh) | 2021-10-09 | 2021-10-09 | 一种甲钴胺注射液的制备方法 |
Publications (2)
Publication Number | Publication Date |
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CN114601792A true CN114601792A (zh) | 2022-06-10 |
CN114601792B CN114601792B (zh) | 2022-10-04 |
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CN202111175737.3A Active CN114601792B (zh) | 2021-10-09 | 2021-10-09 | 一种甲钴胺注射液的制备方法 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116077431A (zh) * | 2023-01-04 | 2023-05-09 | 石家庄四药有限公司 | 一种甲钴胺注射液及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000281562A (ja) * | 1999-03-30 | 2000-10-10 | Taisho Pharmaceut Co Ltd | ゲル状組成物 |
EP2384742A1 (en) * | 2010-05-03 | 2011-11-09 | The Jordanian Pharmaceutical Manufacturing Co. | Pharmaceutical excipient, method for its preparation and use thereof |
CN102895200A (zh) * | 2012-11-02 | 2013-01-30 | 湖北人民制药有限公司 | 甲钴胺冻干组合物及其制备方法 |
-
2021
- 2021-10-09 CN CN202111175737.3A patent/CN114601792B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000281562A (ja) * | 1999-03-30 | 2000-10-10 | Taisho Pharmaceut Co Ltd | ゲル状組成物 |
EP2384742A1 (en) * | 2010-05-03 | 2011-11-09 | The Jordanian Pharmaceutical Manufacturing Co. | Pharmaceutical excipient, method for its preparation and use thereof |
CN102895200A (zh) * | 2012-11-02 | 2013-01-30 | 湖北人民制药有限公司 | 甲钴胺冻干组合物及其制备方法 |
Non-Patent Citations (2)
Title |
---|
林冠雄: "甲钴胺注射液制剂处方及工艺的研究", 《海峡药学》 * |
梁宝臣等: "甲钴胺溶解度的测定和关联", 《广州化工》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116077431A (zh) * | 2023-01-04 | 2023-05-09 | 石家庄四药有限公司 | 一种甲钴胺注射液及其制备方法 |
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Publication number | Publication date |
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CN114601792B (zh) | 2022-10-04 |
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Address after: 100025 1703, 14th floor, No.97 Sili, Balizhuang, Chaoyang District, Beijing Patentee after: Beijing huizhiheng Biotechnology Co.,Ltd. Patentee after: Jilin Huisheng Biopharmaceutical Co.,Ltd. Address before: 100025 1703, 14th floor, No.97 Sili, Balizhuang, Chaoyang District, Beijing Patentee before: Beijing huizhiheng Biotechnology Co.,Ltd. Patentee before: Jilin Huisheng biopharmaceutical Co.,Ltd. |
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CP01 | Change in the name or title of a patent holder | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method for methylcobalamin injection Effective date of registration: 20231013 Granted publication date: 20221004 Pledgee: Jilin Bank Co.,Ltd. Tonghua Meihekou Branch Pledgor: Jilin Huisheng Biopharmaceutical Co.,Ltd. Registration number: Y2023220000102 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20221004 Pledgee: Jilin Bank Co.,Ltd. Tonghua Meihekou Branch Pledgor: Jilin Huisheng Biopharmaceutical Co.,Ltd. Registration number: Y2023220000102 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method for methylcobalamin injection Granted publication date: 20221004 Pledgee: Industrial and Commercial Bank of China Limited Meihekou Branch Pledgor: Jilin Huisheng Biopharmaceutical Co.,Ltd. Registration number: Y2024220000070 |