CN1140058A - Slow-release microsphere powder injection of androgenic hormone, its preparing method and use - Google Patents
Slow-release microsphere powder injection of androgenic hormone, its preparing method and use Download PDFInfo
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- CN1140058A CN1140058A CN 96117506 CN96117506A CN1140058A CN 1140058 A CN1140058 A CN 1140058A CN 96117506 CN96117506 CN 96117506 CN 96117506 A CN96117506 A CN 96117506A CN 1140058 A CN1140058 A CN 1140058A
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- Prior art keywords
- microsphere
- hormone
- injectable powder
- injection
- release
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- 239000004005 microsphere Substances 0.000 title claims abstract description 46
- 239000003098 androgen Substances 0.000 title claims abstract description 19
- 238000002347 injection Methods 0.000 title claims abstract description 16
- 239000007924 injection Substances 0.000 title claims abstract description 16
- 239000000843 powder Substances 0.000 title claims description 30
- 238000000034 method Methods 0.000 title claims description 14
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims abstract description 18
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 11
- 239000004626 polylactic acid Substances 0.000 claims abstract description 11
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 229960003604 testosterone Drugs 0.000 claims abstract description 5
- 235000010489 acacia gum Nutrition 0.000 claims abstract description 4
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims abstract description 4
- 229920000159 gelatin Polymers 0.000 claims abstract description 4
- 235000019322 gelatine Nutrition 0.000 claims abstract description 4
- 239000007951 isotonicity adjuster Substances 0.000 claims abstract description 4
- 239000005556 hormone Substances 0.000 claims description 26
- 229940088597 hormone Drugs 0.000 claims description 26
- 238000013270 controlled release Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 9
- 208000035126 Facies Diseases 0.000 claims description 8
- 229920000954 Polyglycolide Polymers 0.000 claims description 8
- 239000004633 polyglycolic acid Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003995 emulsifying agent Substances 0.000 claims description 6
- 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 5
- 239000008103 glucose Substances 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 5
- 238000004659 sterilization and disinfection Methods 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000012875 nonionic emulsifier Substances 0.000 claims description 4
- 229920000151 polyglycol Polymers 0.000 claims description 4
- 239000010695 polyglycol Substances 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- VOCBWIIFXDYGNZ-IXKNJLPQSA-N testosterone enanthate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC2 VOCBWIIFXDYGNZ-IXKNJLPQSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000010255 intramuscular injection Methods 0.000 claims description 2
- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 239000008227 sterile water for injection Substances 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 239000008346 aqueous phase Substances 0.000 claims 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 2
- 239000012567 medical material Substances 0.000 claims 2
- 229930091371 Fructose Natural products 0.000 claims 1
- 239000005715 Fructose Substances 0.000 claims 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims 1
- 229920000193 polymethacrylate Polymers 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 9
- 239000001828 Gelatine Substances 0.000 abstract 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 abstract 1
- 239000003163 gonadal steroid hormone Substances 0.000 abstract 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 abstract 1
- 239000011859 microparticle Substances 0.000 abstract 1
- 239000002245 particle Substances 0.000 description 5
- 239000000376 reactant Substances 0.000 description 4
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003519 biomedical and dental material Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 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
- 239000003921 oil Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 108700012941 GNRH1 Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229940124566 female contraceptive agent Drugs 0.000 description 1
- 239000003037 female contraceptive agent Substances 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
A powdered injection of slow-released androgen microparticles for contraception without any by-effect common caused by sex hormone medicine contains the microsphere consisting of polylactic acid, polyglycollic acid, polylactic acid-polyethylene glycol, polyglycollic acid-polyethylene glycol, polylactic acid-polyglycollic acid and polyamino acid, gelatine, arabic gum, which contains testosterone, testosteron propioate and testosteron enanthate, and isotonic agent.
Description
The present invention is a kind of slow-release microsphere powder injection of androgenic hormone and its production and use, belongs to biomedical sector.
Increasing rapidly of world population, brought more and more heavier pressure for resource, environment, economic development, hindered developing rapidly of World Economics, restricted the raising of developing countries' living standards of the people, therefore, how effectively the control population excessively rapid growth becomes global key subjects just day by day.
Practicing family planning is the fundamental state policy of China, over a long time, China's family planning all is applied as the master with the women from method of birth control, utensil, medicine, scientific research, and is applicable to that method of birth control that the male uses except that sticking stifled, ligation, condom, does not still have other better method.The androgen long-acting slow-release microsphere powder injection of our development, utilize exogenous androgen that the secretion of hypothalamus gonadotropin releasing hormone (GRH) and the secretion of pituitary interstitial cell stimulating hormone (LH) are regulated in the negative feedback that hypothalamus forms, and then utilize the growth of human body LH modulability glandular cell and the purpose that secretion reaches male contraception.This method is owing to eliminated the caused problems at aspects such as operation misery, fertility recoverabilities of methods such as present commonly used gluing blocked up, ligation, have safe and reliable, simple and easy to do, fertility such as can answer at advantage, therefore, the number that may make the male initiatively participate in birth control further increases, and will produce important social benefit and economic benefit.
The existing recent two decades history of sustained-release micro-spheres research of macromolecule such as polylactic acid and polyglycolic acid Biodegradable material packaging medicine.Just there is the seventies PLA to contain the contraceptive microsphere of luteinizing hormone-releasing hormone and is the peaceful microsphere of Du Min of carrier with the Polyethylene Glycol.The medicine of PLA that recent two decades makes and polyglycolic acid parcel is more and more, as the implantation Polyethylene Glycol erythromycin controlled release agent of treatment sand holes, the PLA insulin controlled release agent of China's Taiwan's scholars.Domestic Zhejiang medical scientific institute also is engaged in the research of polylactic acid and copolymer inclusion female contraceptive agent thereof.But do not see the report that has the androgen slow release long-acting injection of making the capsule material with the copolymer of polylactic acid or lactic acid and glycolic to be used for male contraception in the document.
We once applied for a patent " a kind of controlled release hormone microsphere injection and preparation method thereof " (patent No. 95111307.0) and " a kind of injecta of delayed hormone microcapsule and preparation method thereof " (patent No. 95111394.1), and the present invention is the development of above two patents and replenishes.
The purpose of this research is that with polylactic acid, polyglycolic acid, polylactic acid-polyglycol, polyglycolic acid-Polyethylene Glycol, polylactic acid-polyglycolic acid, polyamino acid, gelatin, arabic gum be material, seek suitable process conditions, the slow-release microsphere powder injection of androgen such as preparation testosterone, androlin, atlatest is used for male contraception.
Technical scheme of the present invention is: the controlled release hormone microsphere injectable powder is by the aseptic microsphere powder constituent that contains the glucose isotonic agent, the consumption of glucose by every milliliter of injection water add 55mg etc. the milliosmolarity input.
The inclusion material of slow-release microsphere powder injection of androgenic hormone of the present invention is biodegradable biomedical material: polylactic acid, polyglycolic acid, polylactic acid-polyglycol, polyglycolic acid-Polyethylene Glycol, polylactic acid-polyglycolic acid, polyamino acid, gelatin, arabic gum, its weight average molecular weight range: 3.0 * 10
4～60.0 * 10
4
If exceed this scope, the hormone microsphere of preparation can not be controlled at 1～12 month scope and discharge medicine, or is difficult to make microsphere to be shaped in the preparation process.
Is androgen such as testosterone, androlin, atlatest as slow-release microsphere powder injection of androgenic hormone of the present invention by the inclusion hormone.The weight ratio of hormone and biomedical material is 1: 0.7～19.
If exceed this scope, hormone can not be aggregated the thing inclusion by process of the present invention, or can not be controlled at 1～12 month scope release time by its hormone of the hormone microsphere of inclusion, or the hormone that microsphere discharged can not satisfy the needs of contraception.
Is oil-in-water type as controlled release hormone microsphere injectable powder of the present invention by inclusion technology.
If do not adopt this inclusion technology, can not obtain controlled release hormone microsphere.
As the organic facies of controlled release hormone microsphere injectable powder of the present invention preparation is dichloromethane, chloroform, ethyl acetate, dioxane, ether, dichloromethane-vegetable oil and the mixed solvent be made up of them; The percetage by weight of polymer inclusion material in organic facies is 5.0～30.0.
Water as controlled release hormone microsphere injectable powder preparation of the present invention is PVA, PVP, PMANa, PANa, CMC aqueous solution, and its percetage by weight is 0.01～10.0.
If exceed this scope, then the thus obtained microsphere particle diameter can not be controlled at below 10 μ, or the too little yield of particle diameter reduces.
Emulsifying agent as controlled release hormone microsphere injectable powder preparation of the present invention is oil phase: the HLB value is 4.5～6.0 nonionic emulsifier; Water .HLB value is 14.0～15.5 nonionic emulsifier, and its percetage by weight in water, oil phase is 0.01～12.0.
If exceed this scope, can not get the following microsphere of particle diameter 10 μ, or the too little yield of particle diameter reduces.
As the organic facies of controlled release hormone microsphere injectable powder preparation of the present invention and the volume ratio of water is 1: 4～100.
If exceed this scope, microsphere can not get fine dispersion, and particle diameter can not be controlled at below 10 μ, or the microsphere dispersion is very good, and productive rate is obviously reduced.
Sterilization method and condition as controlled release hormone microsphere injectable powder of the present invention are: oxirane was sterilized 48 hours down at 20～40 ℃, and residual ethylene oxide content is less than 5ppm.
If residual ethylene oxide content is then harmful to health greater than 5ppm.
Controlled release hormone microsphere injectable powder of the present invention injects sterilized water for injection earlier, injects in the body injecting method: intramuscular injection behind the mix homogeneously.
The controlled release hormone microsphere injectable powder that adopts preparation method of the present invention to make is a kind of biomedical material preparation that contains androgen, and its purposes is to be used for the androgen contraception.Because said preparation has the effect of slow release, has not only brought convenience to the patient aspect medication, and also avoided because of long-term a large amount of various side effect of using hormone medicine to cause.
Be embodiments of the invention below.Provide following example explanation the present invention, do not limit its protection domain.
Example 1: with the 200mg testosterone, the 200mg polylactic acid is dissolved in the 3ml dichloromethane, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 10%PVA that 300ml includes the 3.5gHLB=14 emulsifying agent, after fully emulsified 1 hour at decompression (0.03MPa) 30 ℃ of following solvent flashings 2 hours, reactant is moved to centrifugalize in the beaker, with distilled water wash reactant three times, oven dry was sterilized 48 hours at 30 ℃ with oxirane in 30 ℃ of vacuum drying ovens, guarantee the following fill of residual ethylene oxide content 5ppm, specification is every and contains medicine microsphere 200mg and 55mg glucose, promptly gets Injectable sterile controlled release hormone microsphere injectable powder after the leak detection.
Example 2: with the 800mg androlin, 2.4g polylactic acid-polyglycol, the 60mgHLB=6 emulsifying agent is dissolved in the 6ml chloroform, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 0.01%PANa that 30ml includes the 30mgHLB=15.5 emulsifying agent, after fully emulsified 1 hour 40 ℃ of following solvent flashings of normal pressure 3 hours, reactant is moved to centrifugalize in the beaker, with distilled water wash reactant three times, sterilized 48 hours at 40 ℃ with oxirane in the oven dry back in 40 ℃ of vacuum drying ovens, guarantee that residual ethylene oxide content is less than the 5ppm fill, specification is every and contains medicine microsphere 200mg and 55mg glucose, leak detection promptly gets Injectable sterile controlled release hormone microsphere injectable powder.
Claims (10)
1. slow-release microsphere powder injection of androgenic hormone is characterized in that this injectable powder is made up of the androgen sustained-release micro-spheres that contains isotonic agent.
2. according to the injectable powder of claim 1, it is characterized in that microsphere inclusion material is for mainly containing biomedical materials such as biodegradable polylactic acid, polyglycolic acid, polylactic acid-polyglycol, polyglycolic acid-Polyethylene Glycol, polylactic acid-polyglycolic acid, polyamino acid, gelatin or arabic gum.
3. according to the injectable powder of claim 1, it is characterized in that being comprised androgen such as hero, atlatest such as testosterone, androlin by the hormone of inclusion.
4. according to the injectable powder of claim 1, the weight that it is characterized in that the androgen sustained-release micro-spheres is 200～400mg, and the release in vitro hormone is 1～12 month, and isotonic agent is glucose, fructose, sodium chloride etc.
5. according to the injectable powder of claim 1, it is characterized in that biodegradable medical material weight average molecular weight range: 3.0 * 10
4～60.0 * 10
4, the percetage by weight that accounts for microsphere is: 40～95, accounted for the percetage by weight of microsphere by the inclusion hormone: 5～60.
6. according to the preparation method of the injectable powder of claim 1, it is characterized in that microsphere inclusion process using oil-in-water type, the volume ratio of organic facies and water is: 1: 4～100.
7. according to the method for claim 6, it is characterized in that the organic facies that adopts in the microsphere inclusion process comprises dichloromethane, chloroform, ethyl acetate, dioxane, ether, dichloromethane-vegetable oil and the mixed liquor of being made up of them; The emulsifying agent that organic facies adopts is: the nonionic emulsifier of HLB=4.5～6.0, consumption are 0.01～12% of organic facies; The percetage by weight of biodegradable medical material in organic facies is: 5.0～30.0; The water that adopts comprises polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), sodium polymethacrylate (PMANa), sodium polyacrylate (PANa), sodium carboxymethyl cellulose (CMC) aqueous solution; PVA, PVP, PMANa, PANa, CMC in the percetage by weight of aqueous phase are: 0.01～10.0; The emulsifying agent of aqueous phase is: the nonionic emulsifier of HLB value=14.0～15.5, consumption are 0.01～12% of water.
8. the purposes of a slow-release microsphere powder injection of androgenic hormone is characterized in that this injectable powder is used for the androgen contraception.
9. according to the injectable powder of claim 1, it is characterized in that injection controlled release hormone microsphere injectable powder adopts epoxyethane sterilization, conditions for sterilization: 20～40 ℃, 48 hours residual ethylene oxide contents are less than 5.0ppm, and injection sterilization liquor uses sterile water for injection.
10. according to the use of the injection of claim 1, it is characterized in that microsphere is suspended in the sterilization liquor injects in the body injecting method: intramuscular injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96117506 CN1140058A (en) | 1996-03-29 | 1996-03-29 | Slow-release microsphere powder injection of androgenic hormone, its preparing method and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96117506 CN1140058A (en) | 1996-03-29 | 1996-03-29 | Slow-release microsphere powder injection of androgenic hormone, its preparing method and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1140058A true CN1140058A (en) | 1997-01-15 |
Family
ID=5124352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96117506 Pending CN1140058A (en) | 1996-03-29 | 1996-03-29 | Slow-release microsphere powder injection of androgenic hormone, its preparing method and use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1140058A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1308034C (en) * | 2004-12-27 | 2007-04-04 | 中山大学 | Method of preparing microsphere of ethoxyl copolymer PLGA in interferon poly acid |
| CN100400032C (en) * | 2004-09-16 | 2008-07-09 | 同济大学 | A kind of preparation method of oil-soluble drug sustained release microsphere |
| RU2429850C2 (en) * | 2005-04-15 | 2011-09-27 | Кларус Терапьютикс, Инк. | Pharmaceutical delivery systems for hydrophobic therapeutic agents and compositions containing it |
-
1996
- 1996-03-29 CN CN 96117506 patent/CN1140058A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100400032C (en) * | 2004-09-16 | 2008-07-09 | 同济大学 | A kind of preparation method of oil-soluble drug sustained release microsphere |
| CN1308034C (en) * | 2004-12-27 | 2007-04-04 | 中山大学 | Method of preparing microsphere of ethoxyl copolymer PLGA in interferon poly acid |
| RU2429850C2 (en) * | 2005-04-15 | 2011-09-27 | Кларус Терапьютикс, Инк. | Pharmaceutical delivery systems for hydrophobic therapeutic agents and compositions containing it |
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