CN113384523A - Production and preparation method of compound amino acid (15) dipeptide (2) injection - Google Patents
Production and preparation method of compound amino acid (15) dipeptide (2) injection Download PDFInfo
- Publication number
- CN113384523A CN113384523A CN202110729770.XA CN202110729770A CN113384523A CN 113384523 A CN113384523 A CN 113384523A CN 202110729770 A CN202110729770 A CN 202110729770A CN 113384523 A CN113384523 A CN 113384523A
- Authority
- CN
- China
- Prior art keywords
- injection
- preparation
- tank
- amino acid
- dipeptide
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- -1 compound amino acid Chemical class 0.000 title claims abstract description 40
- 238000002347 injection Methods 0.000 title claims abstract description 27
- 239000007924 injection Substances 0.000 title claims abstract description 27
- 108010016626 Dipeptides Proteins 0.000 title claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
- 235000001014 amino acid Nutrition 0.000 claims abstract description 27
- 229940024606 amino acid Drugs 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 239000001301 oxygen Substances 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 239000008215 water for injection Substances 0.000 claims abstract description 16
- 238000011049 filling Methods 0.000 claims abstract description 15
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 13
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000007788 liquid Substances 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 12
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 claims abstract description 11
- 238000001125 extrusion Methods 0.000 claims abstract description 11
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 claims abstract description 11
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 10
- 239000004220 glutamic acid Substances 0.000 claims abstract description 10
- 108010087823 glycyltyrosine Proteins 0.000 claims abstract description 10
- 239000004475 Arginine Substances 0.000 claims abstract description 9
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 9
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 9
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 9
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 9
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 9
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 9
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 9
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004473 Threonine Substances 0.000 claims abstract description 9
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 9
- RRNJROHIFSLGRA-JEDNCBNOSA-N acetic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.NCCCC[C@H](N)C(O)=O RRNJROHIFSLGRA-JEDNCBNOSA-N 0.000 claims abstract description 9
- 235000004279 alanine Nutrition 0.000 claims abstract description 9
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 9
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 9
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 9
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229960000310 isoleucine Drugs 0.000 claims abstract description 9
- 229960005357 lysine acetate Drugs 0.000 claims abstract description 9
- 229930182817 methionine Natural products 0.000 claims abstract description 9
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004474 valine Substances 0.000 claims abstract description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 6
- 230000001954 sterilising effect Effects 0.000 claims abstract description 6
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract description 5
- CUYLIWAAAYJKJH-RYUDHWBXSA-N Gly-Glu-Tyr Chemical group NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CUYLIWAAAYJKJH-RYUDHWBXSA-N 0.000 claims abstract description 5
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 238000007789 sealing Methods 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000007731 hot pressing Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 26
- 239000000463 material Substances 0.000 claims description 11
- 239000002994 raw material Substances 0.000 claims description 11
- 239000002158 endotoxin Substances 0.000 claims description 9
- 238000002834 transmittance Methods 0.000 claims description 8
- PNMUAGGSDZXTHX-BYPYZUCNSA-N Gly-Gln Chemical compound NCC(=O)N[C@H](C(O)=O)CCC(N)=O PNMUAGGSDZXTHX-BYPYZUCNSA-N 0.000 claims description 6
- 230000004888 barrier function Effects 0.000 claims description 6
- 108010010147 glycylglutamine Proteins 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 5
- 239000002250 absorbent Substances 0.000 claims description 4
- 230000002745 absorbent Effects 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 244000005700 microbiome Species 0.000 claims description 3
- 238000009461 vacuum packaging Methods 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 24
- 230000008569 process Effects 0.000 description 20
- 229910052799 carbon Inorganic materials 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 8
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
- 238000005422 blasting Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 3
- 235000016236 parenteral nutrition Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000009924 canning Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000002906 medical waste Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010034016 Paronychia Diseases 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 108010010096 glycyl-glycyl-tyrosine Proteins 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
Classifications
-
- 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
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/10—Bag-type containers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a production and preparation method of compound amino acid (15) dipeptide (2) injection, which comprises the following steps: adding water for injection to 70-80% of the total amount, continuously charging nitrogen, and heating to above 80 ℃; feeding citric acid, leucine, valine, threonine, tryptophan, arginine, alanine, isoleucine, phenylalanine, methionine, lysine acetate, histidine, proline, serine and aspartic acid in a closed feeding tank, and stirring for dissolving; cooling to below 60 deg.C, adding glutamic acid, glycyl glutamyl, and glycyl tyrosine; stirring to dissolve, adding water for injection to full dose, and adding citric acid to adjust pH to 5.5-6.0. Filling the liquid medicine into a three-layer co-extrusion transfusion film bag, and sealing; carrying out hot-pressing sterilization and packaging on the filled sample; the preparation process controls the dissolved oxygen and residual oxygen of the liquid medicine. The invention is beneficial to ensuring the quality stability of the product in the period of validity and the safety of clinical medication.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a method for producing and preparing compound amino acid (15) dipeptide (2) injection, belonging to the technical field of parenteral nutrition preparations.
Background
The compound amino acid (15) dipeptide (2) injection is a parenteral nutrition drug, is suitable for patients who can not take orally or supply nutrition through intestinal tracts, can not meet the requirement of nutrition supply through the routes, and is particularly suitable for patients with moderate to severe catabolic conditions.
This product was developed by the company felon yusbane, trade name: glamin (Validago), approved 5 months in 1995, was marketed in Germany, Switzerland, Sweden, Finland, Denmark, Austria. The import registration is first approved in China in 4 months in 2004.
However, the original product may have the problems of excessive aluminum salt, excessive oxidation degradation of impurities of amino acid products, decreased light transmittance of the product during placement, and the like.
Disclosure of Invention
Based on the technical background: the invention provides a production preparation method of compound amino acid (15) dipeptide (2) injection, which can effectively solve the problems of oxidative degradation and overproof aluminum salt of a product, so that the product meets the requirements of FDA (food and drug administration) on parenteral nutrition preparations, and the content of the aluminum salt can be controlled below 25 mu g/L; the preparation process adopts a direct dilution preparation method and an activated carbon-free process, so that the product safety is improved, the treatment of medical wastes (activated carbon) is reduced, and the environmental protection is facilitated; 0.25g/L citric acid is added before feeding of each amino acid, which is beneficial to dissolving the amino acid and saves the production and preparation time.
The invention is realized by the following technical scheme:
a method for preparing compound amino acid (15) dipeptide (2) injection comprises the following steps:
step A: starting a preparation tank for stirring, adding water for injection into the preparation tank to 70-80% of the total amount, continuously filling nitrogen, and heating to more than 80 ℃;
and B: feeding citric acid, leucine, valine, threonine, tryptophan, arginine, alanine, isoleucine, phenylalanine, methionine, lysine acetate, histidine, proline, serine and aspartic acid in a closed feeding tank, and stirring for dissolving;
and C: cooling to below 60 deg.C, adding glutamic acid, glycyl glutamyl, and glycyl tyrosine; stirring to dissolve, adding water for injection to full dose, and adding citric acid to adjust pH to 5.5-6.0.
Step D: filling the liquid medicine into a three-layer co-extrusion transfusion film bag, and sealing;
step E: and (5) carrying out hot-pressing sterilization on the filled sample.
Step F: filling the sterilized sample and the oxygen absorbent into a barrier bag for vacuum packaging;
the preparation process controls the dissolved oxygen content of the liquid medicine to be less than or equal to 3mg/L and the residual oxygen content to be less than or equal to 1 percent.
Further preferably, in the step B, the citric acid is added in an amount which meets the requirement that the concentration of the citric acid in the current water for injection is 0.25 g/L.
More preferably, in step B and step C, the composition of the amount of each raw material charged, calculated as a total amount of 500ml of water for injection, is as follows: 3.95g leucine, 3.65g valine, 2.80g threonine, 0.95g tryptophan, 5.65g arginine, 8.00g alanine, 2.80g glutamic acid, 2.80g isoleucine, 2.93g phenylalanine, 2.8g methionine, 6.35g lysine acetate, 3.40g histidine, 3.40g proline, 2.25g serine, 1.70g aspartic acid, 1.73g glycyl tyrosine, 15.14g glycyl glutamine.
Further preferably, in step E, the filled sample is sterilized by autoclaving at 121 ℃ for 8 min.
Preferably, in the step B and the step C, the light transmittance of each raw material solution is controlled to be not lower than 98.5%, and the internal control standard strictly in Chinese pharmacopoeia is established to control the limit of bacterial endotoxin and microorganism.
Further preferably, the control of bacterial endotoxin in the three-layer co-extrusion transfusion film bag-making inner bag is less than 0.25 EU.
Further preferably, in the step B, the feeding method by using the closed feeding tank is as follows:
installing a closed feeding tank on a feeding port of the preparation tank, and connecting nitrogen, water for injection and a pressure gauge on the closed feeding tank;
before feeding, checking and confirming whether a butterfly valve below a closed feeding tank is closed completely;
opening a pressure relief valve on the closed feeding tank to relieve pressure, opening a tank cover to feed materials, closing the closed feeding tank cover after a closed feeding tank is filled, vacuumizing the preparation tank, opening nitrogen of the closed feeding tank, opening a butterfly valve of the closed feeding tank, and conveying the raw materials into the thin preparation tank; and closing a butterfly valve of the closed feeding tank after the raw materials are fed, and completing feeding.
The invention has the following advantages and beneficial effects:
1. the preparation process of the invention adopts a direct dilution preparation method and an activated carbon-free process. The conventional amino acid preparation method comprises concentrated preparation and diluted preparation, and the one-step diluted preparation method can reduce the operation link, save the preparation time and reduce the microbial pollution risk. In addition, the active carbon has good pyrogen adsorption and decoloration effects. The active carbon is widely used in the production process of high-capacity injection, but new impurities are introduced into the product due to the use of the active carbon, so that the safety risk and the pressure of environment-friendly treatment are brought, and in addition, the active carbon has stronger adsorption capacity on tryptophan and influences on the content of the tryptophan. Therefore, the safety of the product can be further ensured by adopting the process without the activated carbon, and in addition, the treatment of medical waste (activated carbon) is reduced, thereby being beneficial to environmental protection.
After the activated carbon is removed, the indexes which have the greatest influence on the product quality are light transmittance and bacterial endotoxin. In order to ensure that the product produced by the production and preparation method is safer and more reliable. The light transmittance, bacterial endotoxin and microorganism of the raw and auxiliary materials for producing the product are all strictly controlled and brought into the internal control standard for control; and controlling bacterial endotoxin (less than 0.25EU) in the inner bag made of the three-layer co-extrusion transfusion film for the outer barrier bag of the packaging material so as to reduce microbial load of products and reduce pyrogen risk. The raw and auxiliary materials and the inner packing material which accord with the internal control standard are adopted to produce three batches of samples according to the production and preparation method, the indexes of properties, light transmittance, bacterial endotoxin, related substances and the like which have large influence on the activated carbon are detected, and the indexes are compared with the samples produced by the carbon production process, and the result shows that the properties, the light transmittance and the bacterial endotoxin of the samples produced and prepared by the method accord with the regulations, are basically consistent with the carbon process, but the tryptophan content is obviously lower than that of the process of the invention when the carbon process is used. The product quality can be ensured by canceling the active carbon on the basis of increasing the internal control standard of the original auxiliary packaging material. Meanwhile, the adsorption influence of the activated carbon on the tryptophan can be avoided.
2. In the invention, citric acid is used as a pH regulator, and as part of amino acid has poor solubility, 0.25g/L of citric acid is added before feeding of each amino acid, which is beneficial to dissolving the amino acid and saves the production and preparation time.
3. The closed feeding tank is adopted for feeding, so that air is prevented from being introduced into the preparation tank in the feeding process, and the possibility of oxidation of the liquid medicine is reduced; controlling the dissolved oxygen of the liquid medicine to be less than 3mg/L and the residual oxygen to be less than 1 percent in the whole process of preparation and filling; the three-layer co-extrusion transfusion film bag is used for packaging the infusion bag by adopting the outer barrier bag (the three-layer co-extrusion transfusion film bag can effectively prevent residual oxygen in an inner packaging container from introducing liquid medicine, is superior to glass bottle packaging, is extremely sensitive to oxygen, is easy to generate degradation impurities, and causes the aluminum salt to exceed the standard.
Drawings
The accompanying drawings, which are included to provide a further understanding of the embodiments of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principles of the invention. In the drawings:
FIG. 1 is a schematic structural view of a three-layer co-extrusion transfusion film bag-making package; reference numbers and corresponding part names in fig. 1: 1-bag body, 2-input pipe orifice, 3-output pipe orifice, 4-medicine adding plug, 5-medicine conveying plug and 6-separation bag.
FIG. 2 is a schematic diagram of a front view structure of a closed feeding tank;
FIG. 3 is a schematic top view of the enclosed feed tank; reference numerals and corresponding part names in fig. 2 and 3: reference numbers and corresponding part names in the drawings: 1-water port for injection, 2-vacuumizing and nitrogen filling port, 3-pressure relief port, 4-hand hole, 5-discharge port and 6-blasting sheet port.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples and accompanying drawings, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not meant to limit the present invention.
Example 1
The embodiment provides a production and preparation method of a compound amino acid (15) dipeptide (2) injection, which is used for preparing 10L of the compound amino acid (15) dipeptide (2) injection, and the specific steps are as follows:
weighing: 2.5g of citric acid (added for the first time), 79.0g of leucine, 73.0g of valine, 56.0g of threonine, 19.0g of tryptophan, 113.0g of arginine, 160.0g of alanine, 56.0g of glutamic acid, 56.0g of isoleucine, 58.5g of phenylalanine, 127.0g of lysine acetate, 68.0g of histidine, 56.0g of methionine, 68.0g of proline, 45.0g of serine, 34.0g of aspartic acid, 34.5g of glycyltyrosine and 302.7g of glycylglutamine.
Preparation: 7000ml of water for injection was measured, continuously charged with nitrogen, and heated to 80 ℃. Adding citric acid (0.25g/L), leucine, valine, threonine, tryptophan, arginine, alanine, isoleucine, phenylalanine, methionine, lysine acetate, histidine, proline, serine, and aspartic acid into a sealed feeding tank, stirring, and dissolving.
Cooling the medicinal liquid to 60 deg.C, and adding glutamic acid, glycyl glutamyl, and glycyl tyrosine. Stirring for dissolving, adding water for injection to 10L, and adding citric acid to adjust pH to 5.8.
Filling: the dissolved oxygen of the liquid medicine is controlled to be less than 3mg/L and the residual oxygen is controlled to be less than 1 percent in the whole preparation and canning process. Filling the liquid medicine into a three-layer co-extrusion transfusion bag, and sealing.
And (3) sterilization: the samples were autoclaved at 121 ℃ for 8 min.
Packaging: and bagging the sterilized product and the oxygen absorbent one by one into a barrier bag for vacuum packaging.
The samples from the 3 th test run were tested according to quality standards and the results are shown in table 1.
TABLE 1 test results of 3 samples prepared in example 1
Example 2
The embodiment provides a production and preparation method of a compound amino acid (15) dipeptide (2) injection, which is used for preparing 2500L of the compound amino acid (15) dipeptide (2) injection and comprises the following specific steps:
weighing: 0.625Kg of citric acid (put for the first time), 19.75Kg of leucine, 14.00Kg of isoleucine, 8.50Kg of aspartic acid, 14.625Kg of phenylalanine, 14.00Kg of methionine, 18.25Kg of valine, 14.00Kg of threonine, 31.75Kg of lysine acetate, 28.25Kg of arginine, 40.00Kg of alanine, 17.00Kg of proline, 11.25Kg of serine, 17.00Kg of histidine, 14.00Kg of glutamic acid, 4.75Kg of tryptophan, 75.675Kg of glycylglutamine, 8.625Kg of glycyltyrosine
Preparation: 1850L of water for injection was added to the preparation tank, and nitrogen was continuously added thereto and the mixture was heated to 80 ℃. Adding citric acid (0.25g/L), leucine, valine, threonine, tryptophan, arginine, alanine, isoleucine, phenylalanine, methionine, lysine acetate, histidine, proline, serine, and aspartic acid into a sealed feeding tank, stirring, and dissolving.
Cooling the medicinal liquid to 60 deg.C, and adding glutamic acid, glycyl glutamyl, and glycyl tyrosine. Stirring for dissolving, adding water for injection to 2500L, and adding citric acid to adjust pH to 5.8.
Filling: the dissolved oxygen of the liquid medicine is controlled to be less than 3mg/L and the residual oxygen is controlled to be less than 1 percent in the whole preparation and canning process. Filling the liquid medicine into a three-layer co-extrusion transfusion bag, and sealing.
And (3) sterilization: the samples were autoclaved at 121 ℃ for 8 min.
Packaging: and bagging the sterilized product and the oxygen absorbent one by one into a barrier bag for vacuum packaging.
The key items of the 3 batches of samples amplified in the test were tested according to the quality standards, and the test results are shown in table 2.
Table 2 results of the tests using 3 batches of samples prepared in example 2
The results in the table show that all indexes of the sample prepared by the invention meet the standard requirements, and related substances are in lower levels.
Further, the three-layer co-extruded infusion film bag-making package used in examples 1 and 2 is shown in fig. 1, and the closed feed tank used is shown in fig. 2. In particular, the amount of the solvent to be used,
as shown in fig. 1, the three-layer co-extrusion film bag-making package for transfusion comprises a transfusion bag body 1, a blocking bag 6 is arranged outside the bag body 1, an input pipe orifice 2 and an output pipe orifice 3 are arranged on the bag body, a medicine adding plug 4 is arranged on the input pipe orifice 2, and a medicine conveying plug 5 is arranged on the output pipe orifice 3.
As shown in figure 2, the closed feeding tank comprises a tank body, wherein the top of the tank body is provided with an injection water port 1, a vacuumizing and nitrogen charging air port 2, a pressure relief port 3, a hand hole 4 and a blasting sheet port 6, and the bottom of the tank body is provided with a discharge port 5 and a blasting sheet port 6. Wherein, water injection mouth 1 is used for throwing the material jar internal water injection to sealed, and evacuation, nitrogen filling gas port 2 are used for to jar interior evacuation and fill nitrogen, and release port 3 is used for connecting and washs in the jar behind the cleaning ball, and hand hole 4 is used for throwing the material in the jar and observing the jar interior condition, and discharge gate 5 is used for exporting the material of throwing in the material jar, and blasting piece mouth 6 is used for filling the safe explosion vent that the nitrogen superpressure was.
The feeding method adopting the closed feeding tank is as follows:
installing a closed feeding tank on a feeding port of the preparation tank, and connecting nitrogen, water for injection and a pressure gauge on the closed feeding tank; before feeding, checking and confirming whether a butterfly valve below a closed feeding tank is closed completely; opening a pressure relief valve on the closed feeding tank to relieve pressure, opening a tank cover to feed materials, closing the closed feeding tank cover after a closed feeding tank is filled, vacuumizing the preparation tank, opening nitrogen of the closed feeding tank, opening a butterfly valve of the closed feeding tank, and conveying the raw materials into the thin preparation tank; and closing a butterfly valve of the closed feeding tank after the raw materials are fed, and completing feeding.
Comparative example 1
The comparison case provides a production and preparation method of compound amino acid (15) dipeptide (2) injection, 2500L of compound amino acid (15) dipeptide (2) injection is prepared by adopting the original process, and the specific steps are as follows compared with the steps in the example 1:
(1) the original process prescription contains sodium bisulfite and active carbon; for sodium bisulfite, when the water temperature is raised to above 80 ℃, sodium bisulfite (0.5g/L) is added firstly, and then each amino acid raw material is added; example 1 sodium bisulfite, activated carbon, was eliminated.
(2) The original process does not adopt a closed feeding tank to feed materials; example 1 a closed batch charging tank was used for the batch charging.
(3) The glutamic acid, glycyl glutamine and glycyl tyrosine of the original process are fed at the temperature of more than 80 ℃; the feeding temperature of the example 1 is below 60 ℃.
(4) After the volume is determined by the original process, adjusting the pH value by using dilute hydrochloric acid, adding active carbon for adsorption for 30min, filtering and filling; example 1 after the volume is fixed, the pH value is adjusted by citric acid, and then the mixture is filtered and filled.
(5) After the volume is determined by the original process, filling the solution into a glass infusion bottle; example 1 was filled in a three-layer co-extruded film bag for infusion, sterilized, filled in a barrier bag together with an oxygen absorbent, and vacuum-sealed.
(6) The original process sterilization condition is 115 ℃, 30 min; example 1 the sterilization conditions were 121 ℃ for 8 min.
TABLE 3 detection results of key indexes of samples produced by the original process
The results of comparing table 1 and table 3 show that the indexes of aluminum salt, related substances (pyroglutamic acid, cyclic glycyl-glutamine, cyclic glycyl-tyrosine), light transmittance and the like of the injection prepared by the process of the embodiment 1 are obviously superior to those of the injection prepared by the original process.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (7)
1. A production and preparation method of compound amino acid (15) dipeptide (2) injection is characterized by comprising the following steps:
step A: starting a preparation tank for stirring, adding water for injection into the preparation tank to 70-80% of the total amount, continuously filling nitrogen, and heating to more than 80 ℃;
and B: feeding citric acid, leucine, valine, threonine, tryptophan, arginine, alanine, isoleucine, phenylalanine, methionine, lysine acetate, histidine, proline, serine and aspartic acid in a closed feeding tank, and stirring for dissolving;
and C: cooling to below 60 deg.C, adding glutamic acid, glycyl glutamyl, and glycyl tyrosine; stirring to dissolve, adding water for injection to full dose, and adding citric acid to adjust pH to 5.5-6.0.
Step D: filling the liquid medicine into a three-layer co-extrusion transfusion film bag, and sealing;
step E: and (5) carrying out hot-pressing sterilization on the filled sample.
Step F: filling the sterilized sample and the oxygen absorbent into a barrier bag for vacuum packaging;
the preparation process controls the dissolved oxygen content of the liquid medicine to be less than or equal to 3mg/L and the residual oxygen content to be less than or equal to 1 percent.
2. The production and preparation method of the compound amino acid (15) dipeptide (2) injection as claimed in claim 1, wherein in the step B, the amount of citric acid added is such that the concentration of citric acid in the current water for injection is 0.25 g/L.
3. The production and preparation method of the compound amino acid (15) dipeptide (2) injection according to claim 1, characterized in that in the steps B and C, the input amount of each raw material is calculated by the total amount of water for injection of 500ml, and the composition is as follows:
3.95g leucine, 3.65g valine, 2.80g threonine, 0.95g tryptophan, 5.65g arginine, 8.00g alanine, 2.80g glutamic acid, 2.80g isoleucine, 2.93g phenylalanine, 2.8g methionine, 6.35g lysine acetate, 3.40g histidine, 3.40g proline, 2.25g serine, 1.70g aspartic acid, 1.73g glycyl tyrosine, 15.14g glycyl glutamine.
4. The method for producing the compound amino acid (15) dipeptide (2) injection according to claim 1, wherein in step E, the filled sample is autoclaved at 121 ℃ for 8 min.
5. The method for producing and preparing the compound amino acid (15) dipeptide (2) injection according to claim 1, wherein in the step B and the step C, the light transmittance of each raw material solution is controlled to be not less than 98.5%, and the internal control standard strict with the chinese pharmacopoeia is established to control the limit of bacterial endotoxin and microorganism.
6. The production and preparation method of the compound amino acid (15) dipeptide (2) injection as claimed in claim 5, wherein the control of bacterial endotoxin in the inner bag made by the membrane for three-layer co-extrusion transfusion is less than 0.25 EU.
7. The method for preparing the compound amino acid (15) dipeptide (2) injection according to claim 1, wherein in the step B, a closed feeding tank feeding method is adopted as follows:
installing a closed feeding tank on a feeding port of the preparation tank, and connecting nitrogen, water for injection and a pressure gauge on the closed feeding tank;
before feeding, checking and confirming whether a butterfly valve below a closed feeding tank is closed completely;
opening a pressure relief valve on the closed feeding tank to relieve pressure, opening a tank cover to feed materials, closing the closed feeding tank cover after a closed feeding tank is filled, vacuumizing the preparation tank, opening nitrogen of the closed feeding tank, opening a butterfly valve of the closed feeding tank, and conveying the raw materials into the thin preparation tank;
and closing a butterfly valve of the closed feeding tank after the raw materials are fed, and completing feeding.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110729770.XA CN113384523B (en) | 2021-06-29 | 2021-06-29 | Production and preparation method of compound amino acid (15) dipeptide (2) injection |
| PCT/CN2022/084967 WO2023273484A1 (en) | 2021-06-29 | 2022-04-02 | Method for producing and preparing compound amino acid (15) dipeptide (2) injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110729770.XA CN113384523B (en) | 2021-06-29 | 2021-06-29 | Production and preparation method of compound amino acid (15) dipeptide (2) injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113384523A true CN113384523A (en) | 2021-09-14 |
| CN113384523B CN113384523B (en) | 2022-06-03 |
Family
ID=77624461
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110729770.XA Active CN113384523B (en) | 2021-06-29 | 2021-06-29 | Production and preparation method of compound amino acid (15) dipeptide (2) injection |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN113384523B (en) |
| WO (1) | WO2023273484A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023273484A1 (en) * | 2021-06-29 | 2023-01-05 | 四川科伦药业股份有限公司 | Method for producing and preparing compound amino acid (15) dipeptide (2) injection |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102718833A (en) * | 2012-05-16 | 2012-10-10 | 江苏诚信制药有限公司 | Preparation method of glycyl-tyrosine |
| CN102805857A (en) * | 2012-08-27 | 2012-12-05 | 北京紫萌同达科技有限公司 | Preparation method of compound amino acid (15) dipeptide (2) injecta |
| CN102988359A (en) * | 2012-12-13 | 2013-03-27 | 天津金耀集团有限公司 | Compound amino acid injection (18AA-I) composition |
| CN103142992A (en) * | 2012-11-13 | 2013-06-12 | 湖北一半天制药有限公司 | Preparation method of compound amino acid injection 15 dipeptide |
| CN103230395A (en) * | 2012-05-18 | 2013-08-07 | 湖北一半天制药有限公司 | Preparation method of compound amino acid injection (15-HBC) |
| US20150086514A1 (en) * | 2012-11-14 | 2015-03-26 | Zaimei JIA | Mesenchymal stem cell injection and preparation method thereof, and application thereof in preparing diabetes drug |
| CN105319282A (en) * | 2014-06-20 | 2016-02-10 | 华仁药业股份有限公司 | Content measurement method of compound amino acid (15) dipeptide (2) injection |
| CN105770852A (en) * | 2014-12-23 | 2016-07-20 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of compound amino acid injection containing peptides |
| CN110404048A (en) * | 2019-09-05 | 2019-11-05 | 复旦大学附属中山医院 | Double peptide injections of a kind of amino acid and its preparation method and application |
| CN110693827A (en) * | 2019-11-22 | 2020-01-17 | 天津金耀集团湖北天药药业股份有限公司 | Compound amino acid dipeptide injection and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103948588A (en) * | 2014-04-28 | 2014-07-30 | 山东齐都药业有限公司 | Compound amino acid injection and preparation technology process thereof |
| CN113384523B (en) * | 2021-06-29 | 2022-06-03 | 四川科伦药业股份有限公司 | Production and preparation method of compound amino acid (15) dipeptide (2) injection |
-
2021
- 2021-06-29 CN CN202110729770.XA patent/CN113384523B/en active Active
-
2022
- 2022-04-02 WO PCT/CN2022/084967 patent/WO2023273484A1/en active Application Filing
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102718833A (en) * | 2012-05-16 | 2012-10-10 | 江苏诚信制药有限公司 | Preparation method of glycyl-tyrosine |
| CN103230395A (en) * | 2012-05-18 | 2013-08-07 | 湖北一半天制药有限公司 | Preparation method of compound amino acid injection (15-HBC) |
| CN102805857A (en) * | 2012-08-27 | 2012-12-05 | 北京紫萌同达科技有限公司 | Preparation method of compound amino acid (15) dipeptide (2) injecta |
| CN103142992A (en) * | 2012-11-13 | 2013-06-12 | 湖北一半天制药有限公司 | Preparation method of compound amino acid injection 15 dipeptide |
| US20150086514A1 (en) * | 2012-11-14 | 2015-03-26 | Zaimei JIA | Mesenchymal stem cell injection and preparation method thereof, and application thereof in preparing diabetes drug |
| CN102988359A (en) * | 2012-12-13 | 2013-03-27 | 天津金耀集团有限公司 | Compound amino acid injection (18AA-I) composition |
| CN105319282A (en) * | 2014-06-20 | 2016-02-10 | 华仁药业股份有限公司 | Content measurement method of compound amino acid (15) dipeptide (2) injection |
| CN105770852A (en) * | 2014-12-23 | 2016-07-20 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of compound amino acid injection containing peptides |
| CN110404048A (en) * | 2019-09-05 | 2019-11-05 | 复旦大学附属中山医院 | Double peptide injections of a kind of amino acid and its preparation method and application |
| CN110693827A (en) * | 2019-11-22 | 2020-01-17 | 天津金耀集团湖北天药药业股份有限公司 | Compound amino acid dipeptide injection and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| LI LI等: "Quantitation of Four Tryptophan-Related Impurities in Compound Amino Acid Injection-18 AA by HPLC-PDA", 《CHROMATOGRAPHIA》 * |
| 危媚，等: "如何保证复方氨基酸注射液的质量", 《海峡药学》 * |
| 梁林: "复方氨基酸(15)双肽(2)注射液的工艺研究与质量评价", 《中国优秀硕士学位论文 医药卫生科技辑》 * |
| 章九云，等: "复方氨基酸(15)双肽(2)注射液制备工艺的优化", 《福建医药杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023273484A1 (en) * | 2021-06-29 | 2023-01-05 | 四川科伦药业股份有限公司 | Method for producing and preparing compound amino acid (15) dipeptide (2) injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113384523B (en) | 2022-06-03 |
| WO2023273484A1 (en) | 2023-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7029752B2 (en) | Plastic container for liquid medicine and method of storing and recovering liquid medicine | |
| CN110638751A (en) | Stable sugammadex sodium injection and preparation method thereof | |
| EP3050556B1 (en) | Process for manufacturing a pharmaceutical preparation containing glatiramer acetate | |
| CN113384523B (en) | Production and preparation method of compound amino acid (15) dipeptide (2) injection | |
| EP2656848A1 (en) | Ready to be infused gemcitabine solution | |
| US20220023238A1 (en) | Process of Manufacturing a Stable, Ready to Use Infusion Bag for an Oxidation Sensitive Formulation | |
| US20240299447A1 (en) | Trace element compositions, methods of making and use | |
| CN105030534B (en) | A kind of sodium bicarbonate injection double-layer sterile packed in flexible pouchy system and preparation method thereof | |
| CN208389001U (en) | A kind of dual-chamber bag for packing alanyl glutamine and amino acid (18) injection | |
| US20230181495A1 (en) | Packaged, sealed container system for stable storage of an oxygen sensitive pharmaceutical formulation | |
| JP2021175713A (en) | Sugammadex, or liquid preparation containing pharmacologically acceptable salt thereof | |
| CN102813622A (en) | Ornidazole sodium chloride injection composition and preparation method thereof | |
| CN111939278B (en) | Sterilization process of higenamine hydrochloride injection | |
| CN101664385B (en) | Ibutilide fumarate injection and preparation method thereof | |
| US20080208141A1 (en) | Plastic Bottle for Oxaliplatin Solution | |
| CN107496349A (en) | Filling ambroxol hydrochloride injection composition of a kind of plastic ampoule and preparation method thereof | |
| CN104288099B (en) | Preparation method of ibuprofen injection | |
| JP2022148893A (en) | Combination container including liquid, container set and manufacturing method for container including liquid | |
| CN108888593B (en) | Atenolol injection and preparation method thereof | |
| CN102357094A (en) | Pharmaceutical composition containing eighteen amino acids | |
| CN106902144B (en) | Preparation method of composition for injection of medium-long-chain fat emulsion, amino acid and glucose and composition | |
| US20190247307A1 (en) | Formulation of l-cysteine hydrochloride amenable to terminal sterilization | |
| RU2134565C1 (en) | Method of preparing parenteral drug for storage | |
| CN102552251A (en) | Pharmaceutical composition containing 17 amino acids | |
| WO2019147755A1 (en) | Manufacturing and packaging of a sterile drug product |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |