CN107982220A - A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof - Google Patents
A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof Download PDFInfo
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- CN107982220A CN107982220A CN201711278152.8A CN201711278152A CN107982220A CN 107982220 A CN107982220 A CN 107982220A CN 201711278152 A CN201711278152 A CN 201711278152A CN 107982220 A CN107982220 A CN 107982220A
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- lysine
- aspirin
- hydrolysis
- injection
- injection composition
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- 239000007924 injection Substances 0.000 title claims abstract description 52
- 238000002347 injection Methods 0.000 title claims abstract description 52
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- 239000004472 Lysine Substances 0.000 title claims abstract description 40
- 230000000655 anti-hydrolysis Effects 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000003002 pH adjusting agent Substances 0.000 claims abstract description 15
- 239000003381 stabilizer Substances 0.000 claims abstract description 13
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 239000000872 buffer Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000008215 water for injection Substances 0.000 claims description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 5
- 229930003268 Vitamin C Natural products 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 235000019154 vitamin C Nutrition 0.000 claims description 5
- 239000011718 vitamin C Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000005261 decarburization Methods 0.000 claims description 4
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000012982 microporous membrane Substances 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 claims description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 235000002710 Ilex cornuta Nutrition 0.000 claims 1
- 241001310146 Ilex cornuta Species 0.000 claims 1
- 235000010326 Osmanthus heterophyllus Nutrition 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- DFIWJEVKLWMZBI-UHFFFAOYSA-M sodium;dihydrogen phosphate;phosphoric acid Chemical compound [Na+].OP(O)(O)=O.OP(O)([O-])=O DFIWJEVKLWMZBI-UHFFFAOYSA-M 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 8
- 206010067484 Adverse reaction Diseases 0.000 abstract description 3
- 230000006838 adverse reaction Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 8
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 6
- 229960004889 salicylic acid Drugs 0.000 description 6
- 239000008354 sodium chloride injection Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000003182 parenteral nutrition solution Substances 0.000 description 4
- 208000001297 phlebitis Diseases 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical class CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 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
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- -1 benzoic acids potassium] salt Chemical class 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
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
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof.The present invention, the aspirin-Al-lysine for injection composition of anti-hydrolysis are included as follows according to the component of mass percent meter：Di-lysine-aspirin 64~74%, pH adjusting agent 6~10% and stabilizer 20~35%.The aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention can be used as common powder-injection, have the advantages that surface is not easy bonding, good fluidity, small, the related content of material of hygroscopicity is few in atmosphere, stability is good, di-lysine-aspirin is can effectively avoid to hydrolyze, reduce the incidence of adverse reaction, improve the security of clinical practice, have a good application prospect and market value, be adapted to industrialized production.
Description
Technical field
The invention belongs to pharmaceutical field, it is more particularly related to a kind of anti-hydrolysis that can be made into common powder-injection
Aspirin-Al-lysine for injection composition and preparation method thereof.
Background technology
Di-lysine-aspirin, chemical name DL-lysine list [2- (acetoxyl group) benzoic acids potassium] salt, is that the DL- of acetylsalicylic acid relies
Propylhomoserin salt, the derivative as aspirin are a kind of antipyretic towns for first electing listing in the seventies by French Egic drugmakers
Pain medicine.The medicine can intramuscular injection or intravenously administrable, clinic is mainly used for fever and the light, pain of moderate.
Rely nitrogen woods that there is good solubility in water, be administered for injection, so as to avoid oral caused stomach and intestine
Road side effect, and curative effect is improved, but di-lysine-aspirin is more unstable in storage process, easily decomposes, salicylic acid content is exceeded matter
The bound requirements of amount standard, this directly affects production and clinical practice.
Di-lysine-aspirin not only can also influence its decomposition to heat, photo-labile, humidity.Some researches show that di-lysine-aspirin is placed in
Easily absorption vapor increases water content in air, and degradation rate is accelerated, content is lower.It is caused to be in storage period decomposed
Free salicylic acid, reduces drug effect.Since free salicylic acid is irritant to human body and mortality, cause to stimulate after there is medication
Property and fatefulue adverse reaction increase, occur muscular death or serious allergic reaction, or even threat to life when serious.
The country there is no in relation to overcoming aspirin-Al-lysine for injection to decompose unstable document or patent report when applying at present.Cause
This is avoided the influence of high temperature and moisture, it is necessary to research and develop a kind of new aspirin-Al-lysine for injection, further play its drug effect and
Adverse reaction is reduced, stability, safety issue during improving aspirin-Al-lysine for injection clinical practice.
The content of the invention
It is an object of the invention to：Overcome existing for existing di-lysine-aspirin easily decompose, the problems such as stability is poor, there is provided
A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof.
In order to realize foregoing invention purpose, the present invention provides a kind of aspirin-Al-lysine for injection composition of anti-hydrolysis, its
Including as follows according to the component of mass percent meter：Di-lysine-aspirin 64~74%, pH adjusting agent 6~10% and stabilizer 20~
35%.
Preferably, the aspirin-Al-lysine for injection composition of above-mentioned anti-hydrolysis is included as follows according to the group of mass percent meter
Point：Di-lysine-aspirin 65-73%, pH adjusting agent 6~9% and stabilizer 23~33%.
Preferably, the pH adjusting agent is selected from buffer, the citric acid-sodium citrate of citric acid-disodium hydrogen phosphate composition
Any one group in the buffer of composition, sodium dihydrogen phosphate-disodium hydrogen phosphate；The stabilizer be selected from vitamin C, glucose,
One or more in trehalose.
It is highly preferred that the buffer solution of selection citric acid-disodium hydrogen phosphate composition selects vitamin C to make as pH adjusting agent
For stabilizer.
Optimal selection as the aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention：It is included as follows according to quality hundred
Divide the component than meter：The buffer and vitamin C 25% that di-lysine-aspirin 67%, citric acid 4%- disodium hydrogen phosphates 4% form.
In order to realize foregoing invention purpose, present invention also offers the aspirin-Al-lysine for injection composition of above-mentioned anti-hydrolysis
Preparation method, it includes the following steps：
S1, add di-lysine-aspirin and stabilizer in water for injection, is stirred to dissolve under aseptic condition；
S2, add activated carbon adsorption decoloration, then filters decarburization；
S3, add pH adjusting agent, and pH is adjusted to 4.5~7.5, with 0.22~0.45 μm of sterile filtering with microporous membrane 2
~3 times；
S4, dehydrated the liquid after filtering, obtains the aspirin-Al-lysine for injection composition of anti-hydrolysis.
When the aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention is dissolved in water for injection, the pH value range of obtained aqueous solution
It is 4.5~7.5.
Preferably, when the aspirin-Al-lysine for injection composition of the anti-hydrolysis is dissolved in water for injection, the pH of obtained aqueous solution
Value scope is 5.0~6.0.
Relative to the prior art, the present invention has the advantages that：
(1) the aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention is as common powder-injection, its appearance, shape, content
More stablize, influence of the factors such as moisture, oxygen, pH, temperature, illumination to di-lysine-aspirin can be avoided as much as, it is effectively anti-
Only di-lysine-aspirin hydrolyzes, and can also reduce the generation in relation to material, and stability is improved, so that wind when reducing injection
Danger.
(2) the aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention and pH value of solution change during parenteral solution compatibility are slow, can
The incidence of phlebitis is reduced, Clinical practice is safer.
Embodiment
In order to become apparent from the purpose of the present invention, technical solution and advantageous effects, with reference to embodiments, to this
Invention is further elaborated.It should be appreciated that the embodiment described in this specification is just for the sake of this hair of explanation
It is bright, be not intended to limit the present invention, the parameter of embodiment, ratio etc. can adaptation to local conditions make a choice and substance had no to result
Influence.
Embodiment 1
The aspirin-Al-lysine for injection composition and one group of injection prepared using lyophilized technique for preparing eight groups of anti-hydrolysis are relied
Ammonia woods, each component and dosage are as follows.According to the component and dosage of lower section A-H groups, di-lysine-aspirin and stabilizer are dissolved
In 1000ml waters for injection, activated carbon adsorption decoloration is added, then filters decarburization.With pH adjusting agent adjust pH value to 4.5~
7.5, with 0.22 μm -0.45 μm of sterile filtering with microporous membrane 2-3 times.Liquid after filtering is filled by dehydration and drying per component
In 1000 vials, the common powder-injection of the aspirin-Al-lysine for injection composition of anti-hydrolysis is obtained, contains in every medicine and relies
Ammonia woods 0.25 or 0.9g.
The amounts of components of the aspirin-Al-lysine for injection prepared using lyophilized technique is as shown in I groups in table 1, and preparation method is such as
Under：Di-lysine-aspirin and mannitol are dissolved in 1000ml waters for injection, activated carbon adsorption decoloration is added, then filters decarburization.
PH value is adjusted to 4.0~7.0 with pH adjusting agent, with 0.228~0.45 μm of sterile filtering with microporous membrane 2~3 times, gained liquid
It is sub-packed in 1000 vials, is put into pre-freeze in freeze drying box, temperature is -40 ± 5 DEG C, when the time is 3 small；After medicine freezes,
Condenser is opened, when condenser temperature reaches -50 DEG C, opens vacuum system, system vacuum is reached 10Pa, when maintenance 1 is small；Open
Dynamic heating unit, makes medicine temperature be maintained at 10-20 DEG C, when the time is 8 small；Medicine is warming up to 35-40 DEG C again, vacuum heat-preserving
When drying 8 is small, aspirin-Al-lysine for injection freeze-dried powder is obtained.
1 nine groups of di-lysine-aspirin pharmaceutical compositions of table
Embodiment 2
Common powder-injection and I group use to the aspirin-Al-lysine for injection composition of the anti-hydrolysis of A-H groups in embodiment 1 is lyophilized
The freeze-dried powder of aspirin-Al-lysine for injection composition prepared by technique carries out the study on the stability under different condition.A-I groups are taken to inject
With di-lysine-aspirin composition, placed 10 days under the conditions of 4500 lx of 60 DEG C of high temperature or illumination, measure the 0th day, 5 days, 10 days it is common
Appearance, solution colour, pH value, related material (salicylic acid), the content's index of powder-injection.Detect solution colour, pH value, related thing
When matter (salicylic acid), content's index, with water for injection 5 or 18ml dissolving embodiment 1 in one bottle (di-lysine-aspirin content 0.25,
0.9g), preparing becomes di-lysine-aspirin parenteral solution 50mg/ml.The testing result of A-I groups preparation refers to table 2 in embodiment 1.In A-I
In group preparation, A-E and I group pharmaceutical compositions are more stable, at different conditions placement 10 days, its solution colour, pH value, containing quantitative change
Change is smaller, and the apparent condition of A groups is best, and white loose shape is still kept after placing 10 days；F-H group di-lysine-aspirins powder injection formulation is unstable
Fixed, related material (salicylic acid) changes greatly, and H groups changes of contents is maximum, G, H group solution changes color.
The stability of 2 nine groups of preparations of table at different conditions
Embodiment 3
Embodiment 1A-I groups are dissolved in 0.9% sodium chloride injection, the di-lysine-aspirin parenteral solution being configured to can directly face
Bed administration.As shown in table 3, after A-I groups and 0.9% sodium chloride injection compatibility, pH value of solution, which reduces speed, to be slowed down, compatibility 15 minutes
Afterwards, 4.0 or so, and changes of contents is small, the related material of A-I groups meets the requirements pH value of solution；And commercially available di-lysine-aspirin is matched somebody with somebody
After 5 15 minutes, changes of contents is larger, and wherein A-C and I groups pH changes and changes of contents are smaller；Commercially available di-lysine-aspirin with
51 it is small when after there is related material and change greatly, and the related material of A-I groups is below commercially available group.A-B groups solution after 1h,
PH value of solution reduces phlebitis risk still greater than 4；A groups solution content changes smaller, with 0.9% sodium chloride injection compatibility more
Stablize.Therefore the aspirin-Al-lysine for injection composition of the anti-hydrolysis of the present invention can effectively reduce di-lysine-aspirin hydrolysis cause pH value of solution compared with
Big change, thereby reduces the phlebitis risk that parenteral solution pH ＜ 4 are brought；Reduce the changes of contents of di-lysine-aspirin at the same time, make
Di-lysine-aspirin and 0.9% sodium chloride injection compatibility are more stable.
Compared with the stability of 3 A-I groups of table and marketed drugs in 0.9% sodium chloride injection
In conclusion the aspirin-Al-lysine for injection composition stability of the anti-hydrolysis prepared by the present invention is good, safe,
It can prevent di-lysine-aspirin hydrolysis from causing the change of pH, content, related material is effectively controlled, occurs when can reduce clinical practice
Phlebitis risk, stability during clinical compatibility can be strengthened.
According to the disclosure and teachings of the above specification, those skilled in the art in the invention can also be to above-mentioned embodiment party
Formula carries out appropriate change and modification.Therefore, the invention is not limited in embodiment disclosed and described above, to this
Some modifications and changes of invention should also be as falling into the scope of the claims of the present invention.In addition, although this specification
In used some specific terms, but these terms are merely for convenience of description, do not limit the present invention in any way.
Claims (10)
1. a kind of aspirin-Al-lysine for injection composition of anti-hydrolysis, it is characterised in that including as follows according to mass percent meter
Component：Di-lysine-aspirin 64~74%, pH adjusting agent 6~10% and stabilizer 20~35%.
2. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 1, it is characterised in that including as follows according to
The component of mass percent meter：Di-lysine-aspirin 65-73%, pH adjusting agent 6~9% and stabilizer 23~33%.
3. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 1, it is characterised in that the pH adjusting agent
Buffer, the sodium dihydrogen phosphate-phosphoric acid of buffer, citric acid-sodium citrate composition selected from citric acid-disodium hydrogen phosphate composition
Any one group in disodium hydrogen.
4. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 3, it is characterised in that the pH adjusting agent
For the buffer of citric acid-disodium hydrogen phosphate composition.
5. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 4, it is characterised in that including as follows according to
The component of mass percent meter：Di-lysine-aspirin 67%, pH adjusting agent 8% and stabilizer 25%；Wherein, the pH adjusting agent is Chinese holly
The buffer that rafter acid 4%- disodium hydrogen phosphates 4% form.
6. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 1, it is characterised in that the stabilizer choosing
One or more from vitamin C, glucose, trehalose.
7. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 6, it is characterised in that the stabilizer is
Vitamin C.
8. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 1, it is characterised in that the anti-hydrolysis
When aspirin-Al-lysine for injection composition is dissolved in water for injection, the pH value range of obtained aqueous solution is 4.5~7.5.
9. the aspirin-Al-lysine for injection composition of anti-hydrolysis according to claim 8, it is characterised in that the anti-hydrolysis
When aspirin-Al-lysine for injection composition is dissolved in water for injection, the pH value range of obtained aqueous solution is 5.0~6.0.
10. the preparation side of the aspirin-Al-lysine for injection composition of anti-hydrolysis described in any one claim in claim 1~9
Method, it is characterised in that include the following steps：
S1, add di-lysine-aspirin and stabilizer in water for injection, is stirred to dissolve under aseptic condition；
S2, add activated carbon adsorption decoloration, then filters decarburization；
S3, add pH adjusting agent, and pH is adjusted to 4.5~7.5, with 0.22~0.45 μm of sterile filtering with microporous membrane 2~3
It is secondary；
S4, dehydrated the liquid after filtering, obtains the aspirin-Al-lysine for injection composition of anti-hydrolysis.
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| CN201711278152.8A CN107982220A (en) | 2017-12-06 | 2017-12-06 | A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof |
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| CN201711278152.8A CN107982220A (en) | 2017-12-06 | 2017-12-06 | A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1640407A (en) * | 2004-01-06 | 2005-07-20 | 李细海 | Anti-thrombus small-dose aspirin injection agent and its preparing method |
| CN1739530A (en) * | 2005-09-12 | 2006-03-01 | 扬州一洋制药有限公司 | Aspirin-Al-lysine for injection |
| CN101780099A (en) * | 2010-02-10 | 2010-07-21 | 邓学峰 | Meglumine adenosine cyclophosphate composite medicament |
| CN104744249A (en) * | 2013-12-31 | 2015-07-01 | 海口天行健药物研究有限公司 | Method for preparing stable salt of aspirin and alkaline amino acid |
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2017
- 2017-12-06 CN CN201711278152.8A patent/CN107982220A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1640407A (en) * | 2004-01-06 | 2005-07-20 | 李细海 | Anti-thrombus small-dose aspirin injection agent and its preparing method |
| CN1739530A (en) * | 2005-09-12 | 2006-03-01 | 扬州一洋制药有限公司 | Aspirin-Al-lysine for injection |
| CN101780099A (en) * | 2010-02-10 | 2010-07-21 | 邓学峰 | Meglumine adenosine cyclophosphate composite medicament |
| CN104744249A (en) * | 2013-12-31 | 2015-07-01 | 海口天行健药物研究有限公司 | Method for preparing stable salt of aspirin and alkaline amino acid |
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Application publication date: 20180504 |