CN1561976A - Garlicin concentrated, solution for supply intravenous after composite solvent dilution - Google Patents
Garlicin concentrated, solution for supply intravenous after composite solvent dilution Download PDFInfo
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- CN1561976A CN1561976A CN 200410014731 CN200410014731A CN1561976A CN 1561976 A CN1561976 A CN 1561976A CN 200410014731 CN200410014731 CN 200410014731 CN 200410014731 A CN200410014731 A CN 200410014731A CN 1561976 A CN1561976 A CN 1561976A
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- Prior art keywords
- garlicin
- injection
- intravenous
- concentrated solution
- dilution
- Prior art date
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- 239000002904 solvent Substances 0.000 title claims abstract description 41
- 239000000243 solution Substances 0.000 title claims abstract description 23
- 238000001990 intravenous administration Methods 0.000 title claims description 15
- 238000010790 dilution Methods 0.000 title claims description 13
- 239000012895 dilution Substances 0.000 title claims description 13
- 239000002131 composite material Substances 0.000 title abstract 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 75
- 238000002347 injection Methods 0.000 claims abstract description 48
- 239000007924 injection Substances 0.000 claims abstract description 48
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 229920005862 polyol Polymers 0.000 claims abstract description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 54
- 239000007788 liquid Substances 0.000 claims description 50
- 239000002202 Polyethylene glycol Substances 0.000 claims description 21
- 229920001223 polyethylene glycol Polymers 0.000 claims description 21
- -1 carbon polyol Chemical class 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000012046 mixed solvent Substances 0.000 claims description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 abstract 1
- 229940090044 injection Drugs 0.000 description 37
- 239000011259 mixed solution Substances 0.000 description 30
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 16
- 229920000053 polysorbate 80 Polymers 0.000 description 16
- 238000012360 testing method Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- JDLKFOPOAOFWQN-VIFPVBQESA-N Allicin Natural products C=CCS[S@](=O)CC=C JDLKFOPOAOFWQN-VIFPVBQESA-N 0.000 description 6
- 240000002234 Allium sativum Species 0.000 description 6
- JDLKFOPOAOFWQN-UHFFFAOYSA-N allicin Chemical compound C=CCSS(=O)CC=C JDLKFOPOAOFWQN-UHFFFAOYSA-N 0.000 description 6
- 235000010081 allicin Nutrition 0.000 description 6
- 235000004611 garlic Nutrition 0.000 description 6
- 238000011160 research Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010017533 Fungal infection Diseases 0.000 description 3
- 208000031888 Mycoses Diseases 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 241000234282 Allium Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010040904 Skin odour abnormal Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- UBAXRAHSPKWNCX-UHFFFAOYSA-N diallyl trisulfide Chemical compound C=CCSSSCC=C UBAXRAHSPKWNCX-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004429 Bacillary Dysentery Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 208000006081 Cryptococcal meningitis Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000498255 Enterobius vermicularis Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 1
- 241000234280 Liliaceae Species 0.000 description 1
- 206010027209 Meningitis cryptococcal Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 208000007074 Trichomonas Vaginitis Diseases 0.000 description 1
- 208000025206 Trichomonas vaginitis urogenital infection Diseases 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 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 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 206010014881 enterobiasis Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 230000000854 inhibitional effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940080526 mannitol injection Drugs 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000005113 shigellosis Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A concentrated garlicin solution used for intravenous injection after diluted by composite solvent contains garlicin, the composite solvent prepared from alcohol and low-carbon polyol and/or polyethanediol, and the non-ionic solubilizer for injection.
Description
Technical field
The present invention relates to the garlicin injection of injection for intravenous after a kind of dilution of double solvent.
Background technology
Garlicin (diallyl trisulfide) has another name called allicin, chemistry allicin by name.Be isolated a kind of reactive compound in the underground bulb of Liliaceae allium Bulbus Allii Allium Satium L., be used for the raw material polyphyly synthetic of the research and the production of injection at present.Modern pharmacological research shows: garlicin has broad-spectrum antifungal and fungicidal action.Garlicin also has effects such as blood fat reducing, blood vessel dilating, atherosclerosis, antiplatelet aggregation, antitumor simultaneously.Because garlicin is antibiotic and fungistatic effect is definite, mainly is to use as anti-infectives.Garlicin injection is one of common formulations clinically.Be applicable to deep fungal and bacterial infection, be used for anti-treating acute and chronic bacillary dysentery and enteritis, pertussis, pulmonary and gastral fungal infection, Candida albicans bacteremia, cryptococcal meningitis, pulmonary tuberculosis etc.Because of its curative effect height, safe, rapid-action, advantage such as have no side effect are widely used in clinical.
At present, the research of the injection of relevant Bulbus Allii or its active component all concentrates on the extraction process of garlicin or it is the technology of the injection of solvent with water.But be under the condition of solvent with water, the garlicin performance is unstable, and under extraneous condition influence, the color of garlicin is easily deepened even the thickness that becomes, and its biological function is also along with reduction.Studies show that the garlicin aqueous solution is comparatively stable under the condition of slant acidity (especially pH5～7) down for room temperature (28 ℃); In different temperature ranges, along with the prolongation of time, garlicin content is all on a declining curve, but temperature is high more, and garlicin content descends fast more.The garlicin injection that with water is solvent is by adjust pH, add antioxidant, reduce the decomposition of garlicin at aspects such as the dark place storages of drying in the air as much as possible as far as possible.But certain garlicin injection (aqueous vehicles) that has gone on the market is carried out quality research, show, store after 12 months, garlicin has decomposed more than 30%.Related substance (impurity) increases.This phenomenon is unfavorable for the secular safe application of garlicin injection liquid product.
Summary of the invention
The object of the present invention is to provide the garlicin concentrated solution of injection for intravenous after a kind of dilution of double solvent, in this double solvent, external condition such as temperature, light descends to the influence of garlicin, can guarantee the chemical constituent allicin long-term stability of garlicin.
Technical scheme of the present invention is: the garlicin concentrated solution of injection for intravenous after a kind of dilution of double solvent, comprise reactive compound garlicin, mixed solvent, injection non-ionic solubilizer, described mixed solvent comprises ethanol, described mixed solvent also comprises at least a in propylene glycol, glycerol, three kinds of solvents of liquid polyethylene glycol, and the content of garlicin is 5～40 mg/ml in the described concentrated solution; The consumption of described mixed solvent should be enough to make described garlicin dissolving and keep stable.
Described garlicin has another name called allicin, chemistry allicin by name.But described garlicin, ethanol, low carbon polyol, liquid polyethylene glycol, water, injection are the medicinal product of injection for intravenous with non-ionic solubilizer.
The injection non-ionic solubilizer is meant that the nonionic of the dissolubility of increased insoluble drug in solvent that can be used for drug administration by injection shows activating agent.Generally comprise: the high-grade aliphatic ester of polyoxyethylene monostearate, sucrose, tween, span, polyoxyethylene castor oil, polyoxyethylene polyoxypropylene block polymer, polyoxyethylene and high fatty alcohol condensation substance.
Take by weighing garlicin and injection non-ionic solubilizer mix homogeneously, add and be pre-mixed the ethanol that makes, the double solvent of several compositions in low carbon polyol, liquid polyethylene glycol and the water, adjust pH, filter yellowish clear and bright solution, embedding is in the container that liquid medicine injection allows to use, sterility test is qualified, and packing promptly.
The present invention compared with prior art, patent 88103251.4 has related to uses 95% ethanol to extract from Bulbus Allii, is mainly the extraction preparation of the garlic injection that contains alcohol; Patent 00117206.9 and 02129468.2 has related to the use supercritical extraction technique and has extracted garlicin, belongs to the preceding working procedure technology.Technology of preparing all about garlic injection is water or contains pure aqueous solution.According to the garlicin injection that patent and related preparations technology make, under the normal condition, it is annual more than 20% that the garlicin decomposition rate still reaches, and related substance (impurity) increases very fast, and product stability is poor.We confirm to adopt double solvent to prepare garlicin injection through after fully studying and groping, and can suppress garlicin preferably and decompose, and improve product stability greatly.Under normal operation, the garlicin decomposition rate is lower than 3% every year.
2, garlicin stability test:
We are according to the related content in two appendix of Chinese Pharmacopoeia version in 2000 " medicine stability experiment instruction principle ", the garlicin injection of our trial-production are comprehensively carried out the study on the stability of garlicin injection.Do accelerated test and long term test.Commercially available a kind of garlicin injection that the same terms was stored 6 months down compares research simultaneously.Totally 3 batches of pilot samples.
40 ℃ of accelerated tests of table 1 garlicin injection are investigated the result
The time lot number is investigated project
Character pH value color clarity content (%)
030316
Little yellow clear liquid 4.83 Y-3 numbers up to specification 104.9
2003.3.19 030317
Little yellow clear liquid 4.80 Y-3 numbers up to specification 104.7
(0 month) 030318
Little yellow clear liquid 4.77 Y-3 numbers up to specification 106.8
030316
Little yellow clear liquid 4.85 Y-3 numbers up to specification 104.7
2003.4.19 030317
Little yellow clear liquid 4.89 Y-3 numbers up to specification 104.3
(1 month) 030318
Little yellow clear liquid 4.91 Y-3 numbers up to specification 105.7
030316
Little yellow clear liquid 4.75 Y-3 numbers up to specification 103.9
2003.5.19 030317
Little yellow clear liquid 4.65 Y-3 numbers up to specification 105.0
(2 months) 030318
Little yellow clear liquid 4.79 Y-3 numbers up to specification 105.5
030316
Little yellow clear liquid 4.87 Y-3 numbers up to specification 102.5
2003.6.19 030317
Little yellow clear liquid 4.89 Y-3 numbers up to specification 105.1
(3 months) 030318
Little yellow clear liquid 4.80 Y-3 numbers up to specification 104.2
030316
Little yellow clear liquid 4.71 Y-3 numbers up to specification 102.6
2003.9.19 030317
Little yellow clear liquid 4.79 Y-3 numbers up to specification 105.3
(6 months) 030318
Little yellow clear liquid 4.76 Y-3 numbers up to specification 104.8
Table 2 garlicin injection long term test is investigated the result
Time is investigated project
Lot number
(moon)
Character pH value color clarity content (%)
030316
Little yellow clear liquid 4.83 Y-3 numbers up to specification 104.9
2003.3.19 030317
Little yellow clear liquid 4.80 Y-3 numbers up to specification 104.7
(0 month) 030318
Little yellow clear liquid 4.77 Y-3 numbers up to specification 106.8
030316
Little yellow clear liquid 4.73 Y-3 numbers up to specification 106.7
2003.6.19 030317
Little yellow clear liquid 4.78 Y-3 numbers up to specification 105.0
(3 months) 030318
Little yellow clear liquid 4.81 Y-3 numbers up to specification 107.5
030316
Little yellow clear liquid 4.87 Y-3 numbers up to specification 104.4
2003.9.19 030317
Little yellow clear liquid 4.85 Y-3 numbers up to specification 105.8
(6 months) 030318
Little yellow clear liquid 4.70 Y-3 numbers up to specification 104.6
Place pilot sample and the every test result contrast of contrast medicine after 6 months under table 3 storage requirement
My company's sample of project contrast medicine
Lot number 20,030,301 030,316 030,317 030318
The little yellow clear liquid of the clear and bright liquid of the little yellow of the clear and bright liquid of little yellow, the clear and bright liquid of little yellow
Character
Body, tool garlic odour body, tool garlic odour tool garlic odour body, tool garlic odour
Discriminating is positive reaction and is positive reaction and is positive reaction and is positive reaction
The color Y-3 Y-3 Y-3 of solution Y-3 number
pH 5.13 4.83 4.80 4.77
Clarity is up to specification
Content (%) 49.8 104.9 104.7 106.8
Conclusion is against regulation up to specification up to specification
The specific embodiment
Below by embodiment technical scheme of the present invention is further described:
The garlicin concentrated solution of injection for intravenous after a kind of dilution of double solvent, comprise reactive compound garlicin, mixed solvent, injection non-ionic solubilizer and medicinal formula adjuvant, described mixed solvent comprises ethanol, the mixture that also comprises low carbon polyol or Polyethylene Glycol or low carbon polyol and Polyethylene Glycol, described low carbon polyol is meant the mixture of propylene glycol or glycerol or propylene glycol and glycerol, described Polyethylene Glycol is meant liquid polyethylene glycol, and the content of garlicin is 5～40 mg/ml in the described concentrated solution; The consumption of described mixed solvent should be enough to make described garlicin dissolving and keep stable.
In the described mixed solvent, the volume ratio of consumption of ethanol is 40%～60%.
Also comprise water in the described mixed solvent, in described mixed solvent, the consumption volume ratio of low carbon polyol is 30～60%, the volume ratio of liquid polyethylene glycol consumption is 0～30%, the consumption volume ratio of water is 0～20%.
Described injection non-ionic solubilizer is one of polyoxyethylene monostearate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil or its mixture;
Employed injection is relevant with the consumption of described reactive compound garlicin with the amount of non-ionic solubilizer, and with respect to 1 gram reactive compound, adding injection is 4～15 to restrain with the amount of non-ionic solubilizer.
The medicinal formula adjuvant comprises the pH regulator agent, can select for use from hydrochloric acid, lactic acid, acetic acid, citric acid, malic acid.The medicinal formula adjuvant can also be an antioxidant, but generally need not use, and can select sodium sulfite or thiourea for use if necessary.Container filling can select 2ml～10ml ampoule or liquid medicine injection to allow the glass container that uses, and can decompose further to slow down garlicin by inflated with nitrogen as conditions permit.As the need sterilization, available 100 ℃ of flowing steams sterilization 30min.The pH value of concentrated solution should be 3.0～5.0.
Embodiment:
(1)
Ethanol 400ml garlicin 10～20g
Propylene glycol 320ml tween 80 60～90ml
Liquid polyethylene glycol 280ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(2)
Ethanol 400ml garlicin 10～20g
Propylene glycol 360ml tween 80 40～90ml
Liquid polyethylene glycol 240ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(3)
Ethanol 400ml garlicin 10～20g
Propylene glycol 400ml tween 80 40～90ml
Liquid polyethylene glycol 200ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(4)
Ethanol 500ml garlicin 10～20g
Propylene glycol 400ml tween 80 40～90ml
Liquid polyethylene glycol 100ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(5)
Ethanol 500ml garlicin 10～20g
Propylene glycol 450ml tween 80 40～90ml
Liquid polyethylene glycol 50ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(6)
Garlicin 10～20g
Ethanol 500ml tween 80 40～90ml
Propylene glycol 500ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(7)
Ethanol 550ml garlicin 10～20g
Propylene glycol 440ml tween 80 40～90ml
Liquid polyethylene glycol 10ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(8)
Garlicin 10～20g
Ethanol 600ml tween 80 40～90ml
Propylene glycol 400ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(9)
Garlicin 10～20g
Ethanol 400ml tween 80 40～90ml
Propylene glycol 600ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(10)
Ethanol 360ml garlicin 10～20g
Propylene glycol 540ml tween 80 40～90ml
Liquid polyethylene glycol 100ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(11)
Ethanol 400ml garlicin 10～20g
Propylene glycol 360ml tween 80 40～90ml
Liquid polyethylene glycol 140ml mixed solution is an amount of
Water 100ml
Form the mixed solution total amount to 1000ml
(12)
Ethanol 500ml garlicin 10～20g
Propylene glycol 300ml tween 80 40～90ml
Liquid polyethylene glycol 50ml mixed solution is an amount of
Water 150ml
Form the mixed solution total amount to 1000ml
(13)
Ethanol 500ml garlicin 10～20g
Propylene glycol 300ml tween 80 40～90ml
Water 200ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(14)
Ethanol 300ml garlicin 10～20g
Propylene glycol 500ml tween 80 40～90ml
Water 200ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
(15)
Ethanol 500ml garlicin 10～20g
Liquid polyethylene glycol 300ml tween 80 40～90ml
Water 200ml mixed solution is an amount of
Form the mixed solution total amount to 1000ml
The garlicin concentrated solution of double solvent of the present invention all makes by following operation: the garlicin and the tween 80 mix homogeneously that take by weighing recipe quantity, the double solvent that adds the ethanol that makes by a certain percentage in advance, low carbon polyol, liquid polyethylene glycol, water mixing composition, adjust pH, add 0.01% (w/v) active carbon again, and add double solvent to full dose, just filter with the titanium rod, pass through the filter element fine straining of 0.45 μ m or 0.22 μ m then, embedding allows in the glass container of use in 2ml～10ml ampoule or liquid medicine injection, sterility test is qualified, and packing promptly.
Correlation test shows: under normal storage requirement, the garlicin concentrated solution of non-water of the present invention can guarantee the chemical constituent allicin long-term stability of garlicin.External condition such as temperature, light obviously descends to the influence of garlicin.
The garlicin concentrated solution of double solvent of the present invention can be diluted in the multiple venous transfusions such as the clinical sodium chloride injection that generally uses, glucose injection, Dextrose and Sodium Chloride Inj., formula mannitol injection liquid, ringer's solution, and methods such as employing intravenous drip are applied to the relevant treatment of human body or animal body.
The garlicin concentrated solution of injection for intravenous after the dilution of the double solvent that the present invention relates to, the same with the garlicin injection of water, ethanol system, multiple coccus, bordetella pertussis, diphtheria corynebacterium, dysentery bacterium, typhoid fever and Salmonella paratyphi, escherichia coli, tubercule bacillus etc. there are inhibition and bactericidal action.Fungal infection there is inhibitory action.Ameba, trichomonas vaginitis, pinworm etc. also there is the inhibition killing action.
Claims (6)
1. the garlicin concentrated solution of injection for intravenous after the dilution of a double solvent, comprise reactive compound garlicin, mixed solvent, injection non-ionic solubilizer, it is characterized in that: described mixed solvent comprises ethanol, described mixed solvent also comprises at least a in propylene glycol, glycerol, three kinds of solvents of liquid polyethylene glycol, and the content of garlicin is 5～40 mg/ml in the described concentrated solution; The consumption of described mixed solvent should be enough to make described garlicin dissolving and keep stable.
2. the garlicin concentrated solution of injection for intravenous after the dilution of double solvent according to claim 1, it is characterized in that: in the described mixed solvent, the volume ratio of consumption of ethanol is 40%～60%.
3, the garlicin concentrated solution of injection for intravenous after the dilution of double solvent according to claim 1 is characterized in that: also comprise water in the described mixed solvent.
4, the garlicin concentrated solution of injection for intravenous after the dilution of double solvent according to claim 3, it is characterized in that: in described mixed solvent, the consumption volume ratio of low carbon polyol is 30～60%, the volume ratio of liquid polyethylene glycol consumption is 0～30%, the consumption volume ratio of water is 0～20%.
5. the garlicin concentrated solution of injection for intravenous after the dilution of double solvent according to claim 1, it is characterized in that: described injection non-ionic solubilizer is one of polyoxyethylene monostearate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil or its mixture;
6. the garlicin concentrated solution of injection for intravenous after the dilution of double solvent according to claim 1, it is characterized in that: employed injection is relevant with the consumption of described reactive compound garlicin with the amount of non-ionic solubilizer, with respect to 1 gram reactive compound, adding injection is 4～15 to restrain with the amount of non-ionic solubilizer.
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| CN 200410014731 CN1237963C (en) | 2004-04-20 | 2004-04-20 | Garlicin concentrated, solution for supply intravenous after composite solvent dilution |
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| CN 200410014731 CN1237963C (en) | 2004-04-20 | 2004-04-20 | Garlicin concentrated, solution for supply intravenous after composite solvent dilution |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574333B (en) * | 2008-11-04 | 2013-06-19 | 沈德铭 | Allitride composition and method for preparing drop therewith for treating nasal cavity infected by microbes and application thereof |
| CN104688676A (en) * | 2013-12-10 | 2015-06-10 | 沈阳药科大学 | Andrographolide concentrated liquid and medical application thereof |
| US20150290323A1 (en) * | 2014-04-11 | 2015-10-15 | Sam Houston State University | Dialkyl trisulfides and formulations of dialkyl trisulfides for use as a cyanide antidote |
-
2004
- 2004-04-20 CN CN 200410014731 patent/CN1237963C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574333B (en) * | 2008-11-04 | 2013-06-19 | 沈德铭 | Allitride composition and method for preparing drop therewith for treating nasal cavity infected by microbes and application thereof |
| CN104688676A (en) * | 2013-12-10 | 2015-06-10 | 沈阳药科大学 | Andrographolide concentrated liquid and medical application thereof |
| CN104688676B (en) * | 2013-12-10 | 2018-03-30 | 沈阳药科大学 | Andrographolide concentrated type liquid formula and its medical usage |
| US20150290323A1 (en) * | 2014-04-11 | 2015-10-15 | Sam Houston State University | Dialkyl trisulfides and formulations of dialkyl trisulfides for use as a cyanide antidote |
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| Publication number | Publication date |
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| CN1237963C (en) | 2006-01-25 |
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