CN101032463A - Sirolimus injection and preparing technique thereof - Google Patents
Sirolimus injection and preparing technique thereof Download PDFInfo
- Publication number
- CN101032463A CN101032463A CN 200710015424 CN200710015424A CN101032463A CN 101032463 A CN101032463 A CN 101032463A CN 200710015424 CN200710015424 CN 200710015424 CN 200710015424 A CN200710015424 A CN 200710015424A CN 101032463 A CN101032463 A CN 101032463A
- Authority
- CN
- China
- Prior art keywords
- sirolimus
- injection
- excipient
- cosolvent
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The sirolimus injection is prepared through the following steps: dissolving sirolimus in pharmaceutically acceptable solvent, adding cosolvent and water for injection via stirring to dissolve, adding excipient via stirring to dissolve, filtering, ultrafiltering to obtain clarified solution without heat source, loading into antibiotic ampule, and freeze drying to obtain freeze dried sirolimus powder. Where, the solvent is ethanol, etc; the cosolvent is soluble polyvinylpyrrolidone, hydroxypropyl-beta-cyclodextrin and/or nicotinamide; the weight ratio between sirolimus and the cosolvent is 1 to 2-5; the excipient is mannitol, lactose, etc; and the weight ratio between sirolimus and the excipient is 1 to 0.5-5. The sirolimus injection of the present invention has stable quality, high bioavailability and high curative effect.
Description
Technical field:
The present invention relates to the injection medicine that antitumor is used, relate in particular to sirolimus injection and preparation technology thereof.
Background technology:
Sirolimus (Sirolimus has another name called rapamycin), at present as the existing commodity listing of immunosuppressive drug, two kinds of dosage form listings of existing abroad oral liquid and tablet, domestic have oral liquid formulation to go on the market.Except that immune suppression function, find that through pharmacological screening it also has tangible anti-tumor activity, can be used for treating multiple solid tumor.The bioavailability of the sirolimus oral liquid of listing is about 15% at present, and the bioavailability of tablet is about 19%.Sirolimus belongs to poorly water soluble drugs, and the dissolubility in water is less, and in aqueous solution or in the mixed liquor of water alcohol to the light and heat instability, be difficult for long term storage.
Summary of the invention:
The objective of the invention is to, overcome the deficiencies in the prior art part, a kind of injection and preparation technology thereof of sirolimus are provided, further improve its bioavailability, its injection has been carried out the prescription screening of system, and the preparation technology of injection has been studied, by sirolimus being carried out the development and the transformation of dosage form, in the hope of go out to improve the injection and the preparation technology thereof of sirolimus bioavailability by various formula developments, comprising the sirolimus lyophilized powder.
Sirolimus injection of the present invention is realized by following method: under cleaning condition, the abundant mixed dissolution of solvent with sirolimus and pharmacology permission, add cosolvent, proper amount of water for injection that pharmacology allows, stirring and dissolving, add excipient again, stirring makes it to dissolve fully, obtains apyrogenic clear liquor through coarse filtration, ultrafiltration, place the control antibiotic bottle, press the freeze-dry process making and promptly get sirolimus lyophilized powder product.
The structural formula of sirolimus of the present invention is as follows:
The used solvent of the present invention is: ethanol, but be not limited to ethanol.
The used hydrotropy material of the present invention is including, but not limited to soluble poly vinylpyrrolidone, hydroxypropyl beta cyclodextrin and nicotiamide, can be that wherein one or more mix and use.
The ratio of sirolimus of the present invention and hydrotropy material is: 1: 2～5
The present invention used excipient is including, but not limited to mannitol, lactose, sorbitol and/or low molecular dextran.
The ratio of sirolimus of the present invention and excipient is: 1: 0.5～5
Clinic trial method of the present invention: this injection is dissolved in 5% glucose solution or 0.9% sodium chloride solution, and intravenous drip is used for the immunosuppressant of human organ transplant or the treatment of solid tumor.
The injection specification that the present invention makes is: every contains 0.1 milligram～20 milligrams of sirolimuss, preferred 2～10 milligrams.
The beneficial effect of the injection of sirolimus of the present invention is that the sirolimus injection steady quality according to preparation technology of the present invention makes is suitable for long term store, and has improved the bioavailability of sirolimus, thereby has improved curative effect.
The specific embodiment:
Now in conjunction with the embodiments, injection and the preparation technology thereof to sirolimus of the present invention is described in detail as follows:
Embodiment 1
Under cleaning condition, 10 gram sirolimuss are added stirring and dissolving in 1000 milliliters of ethanol, add soluble poly vinylpyrrolidone 30 grams, add 1000 milliliters of waters for injection, stirring and dissolving adds 8 gram mannitol again, after stirring is dissolved fully, through coarse filtration, ultrafiltration, obtain apyrogenic settled solution, place the control antibiotic bottle, make the 2mg/ bottle by freeze-dry process, the 5mg/ bottle, the product of 10mg/ bottle.
Embodiment 2
Under cleaning condition, 10 gram sirolimuss are added stirring and dissolving in 500 milliliters of ethanol, add nicotiamide 20 grams, add 1000 milliliters of waters for injection, stirring and dissolving adds 8 gram mannitol again, after stirring is dissolved fully, through coarse filtration, ultrafiltration, obtain apyrogenic settled solution, place the control antibiotic bottle, make the 1mg/ bottle by freeze-dry process, the 5mg/ bottle, the product of 10mg/ bottle.
Embodiment 3
Under cleaning condition, 10 gram sirolimuss are added stirring and dissolving in 1000 milliliters of ethanol, add soluble poly vinylpyrrolidone 20 grams, add 1000 milliliters of waters for injection, stirring and dissolving adds 15 gram sorbitol again, after stirring is dissolved fully, through coarse filtration, ultrafiltration, obtain apyrogenic settled solution, place the control antibiotic bottle, make the 5mg/ bottle by freeze-dry process, the 10mg/ bottle, the product of 20mg/ bottle.
The test of sirolimus injection immunosuppressant drug effect:
Sirolimus is to the effect of mice delayed hypersensitivity (DTH): through lumbar injection 1 successive administration 8d every day.But injection sirolimus dosage is 3, strong inhibition cellular immunization DTH reaction (P＜0.01) during 10mg/kg, and median effective dose ED50 is 2mg/kg.
Sirolimus is to the effect of rat local graft versus host reaction (GvHR): through lumbar injection 1 continuous 5d every day.Injection sirolimus dosage is 1,3, the local GvHR of rat is had significant inhibitory effect (P＜0.01, P＜0.05) during 10mg/kg.
Claims (2)
1, sirolimus injection is characterized in that containing cosolvent, excipient that sirolimus and pharmacology allow; The ratio of described sirolimus and hydrotropy material is: 1: 2～5; The ratio of described sirolimus and excipient: 1: 0.5～5.
2, the described sirolimus injection of claim 1, it is characterized in that preparation technology is under cleaning condition, the abundant mixed dissolution of solvent with sirolimus and pharmacology permission, add cosolvent, proper amount of water for injection that pharmacology allows, stirring and dissolving adds excipient again, stirring makes it to dissolve fully, obtain apyrogenic clear liquor through coarse filtration, ultrafiltration, place the control antibiotic bottle, press the freeze-dry process making and promptly get sirolimus injection of the present invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710015424 CN101032463A (en) | 2007-04-19 | 2007-04-19 | Sirolimus injection and preparing technique thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710015424 CN101032463A (en) | 2007-04-19 | 2007-04-19 | Sirolimus injection and preparing technique thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101032463A true CN101032463A (en) | 2007-09-12 |
Family
ID=38729330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710015424 Pending CN101032463A (en) | 2007-04-19 | 2007-04-19 | Sirolimus injection and preparing technique thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101032463A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109431997A (en) * | 2018-12-20 | 2019-03-08 | 武汉科福新药有限责任公司 | A kind of rapamycin locally injecting preparation and preparation method thereof |
-
2007
- 2007-04-19 CN CN 200710015424 patent/CN101032463A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109431997A (en) * | 2018-12-20 | 2019-03-08 | 武汉科福新药有限责任公司 | A kind of rapamycin locally injecting preparation and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101290626B1 (en) | Pharmaceutical formulations comprising voriconazole and processes for preparation thereof | |
| KR101772399B1 (en) | Liposome having inner water phase containing sulfobutyl ether cyclodextrin salt | |
| CN102512399B (en) | Long-acting naltrexone implant and preparation method thereof | |
| US11357728B2 (en) | Liposome having inner water phase containing sulfobutyl ether cyclodextrin salt | |
| CA3048554A1 (en) | Composition of mannuronic diacid | |
| CN103655486B (en) | Sirolimus microemulsion particles and its preparation method and application | |
| EP2868316B1 (en) | Pharmaceutical composition containing fimasartan and hydrochlorothiazide | |
| WO2007006197A1 (en) | Use of levo-ornidazole for preparing antiparasitic infection drug | |
| CN102125547A (en) | Pharmaceutical composition containing gambogic acid medicament and preparation method thereof | |
| CN102614491A (en) | Pharmaceutical composition containing echinocandin antifungal agent micafungin, its preparation method and application | |
| CN102481281A (en) | Dronedarone solid dispersion and preparation method thereof | |
| CN101756897B (en) | Clindamycin hydrochloride injection and preparation method thereof | |
| CN102614492B (en) | Liquid pharmaceutical composition containing echinocandin antifungal agent micafungin | |
| CN101632662B (en) | Sirolimus preparation and preparation process thereof | |
| CN101032463A (en) | Sirolimus injection and preparing technique thereof | |
| KR101439635B1 (en) | Pharmaceutical composition containing entecavir having enhanced stability and preparation method thereof | |
| CN110787125B (en) | Aprepitant nano preparation and preparation method thereof | |
| CN1437942A (en) | Vinorebin powder injection and preparation method | |
| CN115463097A (en) | Preparation process of tacrolimus slow-release intermediate particles | |
| CN102512395B (en) | Huperzine osmotic-pump controlled release tablet | |
| CN106902097A (en) | A kind of pharmaceutical composition for improving drug bioavailability | |
| CN101190937B (en) | Compound with liver-protecting activity | |
| CN1817868A (en) | Group of ornidazole deriative for preventing anaerobe infection and production thereof | |
| CN104248636A (en) | Sirolimus preparation and preparation method thereof | |
| CN1615878A (en) | Linwzolid powder injection and preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |