CN1019266B - Preparation of artemisia apiacea ester for injection - Google Patents
Preparation of artemisia apiacea ester for injectionInfo
- Publication number
- CN1019266B CN1019266B CN85108105A CN85108105A CN1019266B CN 1019266 B CN1019266 B CN 1019266B CN 85108105 A CN85108105 A CN 85108105A CN 85108105 A CN85108105 A CN 85108105A CN 1019266 B CN1019266 B CN 1019266B
- Authority
- CN
- China
- Prior art keywords
- artesunate
- injection
- preparation
- ester
- injections
- 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.)
- Expired
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention belongs to the preparation of antimalarial artesunate for injections. Artesunate is effective antimalarial. The artesunate for injections has the advantages of convenient operation, low toxic effect and side effect, etc., and takes effect rapidly. The artesunate for injections is favorable to the rescue of malignant malaria. The present invention introduces a method for preparing the artesunate for injections. The quality of the artesunate for injections prepared by the method is stable, and the artesunate for injections can be stored for two years at a room temperature.
Description
The invention belongs to the preparation of antimalarial artemisia apiacea ester for injection.
Plasmodium has produced Drug resistance to existing with antimalarials such as chloroquines since the sixties in this century, and the popular difficulty day by day of control malaria is studied the main task that the novel new drug that can treat anti-chloroquine subtertian malaria becomes world's antimalarial research.
Early seventies, unit cooperating research such as China institute of medical instruments and apparatus extract malaria active ingredient arteannuin (Artemisinine) and get chemical constitution clear from feverfew Herba Artemisiae annuae (Artemisia annua L.), carry out a large amount of pharmacological researches then, illustrate it have antimalarial effect good, absorb fast, distribute wide, drain fast, do not have characteristics such as savings, after a large amount of clinical confirmation curative effects are reliable, but there is certain relapse rate, causes domestic and international attention.Units concerned's cooperative groups is found multiple derivant such as dihydroartemisinine (Dihydro-Artemisinine) again subsequently, Artemether (Artemether), artesunate derivants such as (Artesunate) is higher than arteannuin curative effect, Artemether is soluble in oil, the artesunate sodium salt is soluble in water, make injection and more can bring into play quick-acting advantages, help rescuing acces pernicieux.Units such as guilin pharmacy factory made artesunate from 1977 and after pharmacology, toxicity and clinical trial in 1980 in Guilin by the Guangxi district State Scientific and Technological Commission, chemical industry office, health bureau preside over be tested and appraised consistent think the sodium artesunate injection use convenient, take effect rapidly, that poison is paid effect is low.
Nineteen eighty-two, China set up arteannuin scientific research steering committee and World Health Organization's malaria chemotherapy group collaborative development, select the sodium artesunate injection as the preferential development project, because find that in tertogenicity test artemisinin-based drug has the absorption tire, intravenous injection easily is accepted as robbing cure, so pay the utmost attention to.
Existing sodium artesunate injection is to utilize in the sodium hydroxide solution to form with artesunate, have serious quality problems because (1) artesunate facile hydrolysis in alkali solution, in sodium hydroxide and the time local alkali partially always arranged may, can cause product hydrolysis, cause the aqueous solution clarity bad.(2) be neutralized into sodium salt, can not separate crystallization and become mixture, have many impurity.(3) aqueous solution lyophilization grade moisture-sensitive.When embedding, need certain hour, water content difference, hydrolysis rate difference as a result owing to the different moisture absorption differences of every ampoule opening time, stability is very poor very inconsistent, and after same lot number was placed some months, it was unclarity that the ampoule that has is dissolved in water, can not use, thereby can't go into operation.
For this reason, we set about researching and solving this product stability, and keep curative effect and easy to use simultaneously, and want to meet the certain quality standard.
The present invention is for utilizing artesunate free acid controlled micro crystallization, and it is that the solvent dissolving forms injection that the time spent adds slkalizer.
Since artesunate be the general crystallite size of hydrophobic compound more than 150 μ, add the slkalizer jolting and be partly dissolved more than 5 minutes and dissolve very slowly, be difficult to practicality.For this reason, must make it controlled micro crystallization, but the meticulous filtration difficulty of crystallite, and surface area increases, the bad research of stability through crystallite granularity and dissolution velocity relation, we think that the crystallite granularity should be between 10-125 μ, need add certain amount of surfactant at recrystallization process, otherwise small amount of crystalline bonding in bulk dissolubility is little, brings the clarity of injection problem without a minute defection, the solution concentration during crystallization, the dilution liquid measure, factor such as solution temperature and mixing speed all can influence crystalline granularity, all will be controlled, and slkalizer is with 5%NaHCO
3Be advisable.The artemisia apiacea ester for injection of so making is aseptic subpackaged, quickens three months content through 37 ℃ of insulations and does not have obvious decline, and clarity is good, and the room temperature operating period can reach 2 years.
At present, in the new antimalarial agent of external report the most promising be mefloquine just in clinical trial, resisting the strain of chloroquine plasmodium has killing action, but easily develop immunity to drugs and cost much higher than artesunate.
Example one
Get 1 kilogram of artesunate raw material and add 8 times of amounts of 95% ethanol, stirring and dissolving, aseptic filtration, filtrate adds in nearly 20 ℃ equivalent sterile distilled water, stir evenly, with in 72 liters of distilled water of this liquid impouring, the limit edged stirs again, treat that solution becomes places half an hour clearly, sieve is again through the sintered filter funnel filtration certainly to cross 100, and crystallization is washed once with distillation, drains, vacuum drying is to doing general yield 90%.
Example two
Get 1 kilogram of artesunate raw material and add 7 times of amount 95% ethanol, stir and to make moltenly, add 1 liter of 95% alcoholic solution of 10% polyoxyethylene (40) stearate again, mixing, aseptic filtration, filtrate adds 5 liters of mixings of sterile distilled water, in the sterile distilled water with 67 liters 25 ℃ of this liquid impourings, drive agitator again, add and treat that solution becomes is clear, place half an hour, filter, drain through sintered filter funnel, the about 10 times of amount distilled water washs of reuse repeatedly, drain, vacuum drying is to doing general yield 94%.
Example three
Get 1 kilogram of artesunate raw material and add 7 times of amounts of 95% ethanol, stirring and dissolving adds 95% of 10% Tween 80 again.1 liter of solution, mixing, aseptic filtration, filtrate adds 5 liters of sterile distilled waters, and mixing is again in the sterile distilled water with 67 liters 25 ℃ of this liquid impourings, drive agitator, treat after adding that solution becomes is clear, place half an hour, filter through sintered filter funnel, drain, the about 10 times of amount distilled water washs of reuse are repeatedly drained, vacuum drying is to doing general yield 94%.
Claims (2)
1, a kind of preparation method of antimalarial artemisia apiacea ester for injection, it is characterized in that artesunate is added 95% ethanol stirring and dissolving of 7 times of amounts, add 10% polyoxyethylene (40) stearate of 1 times of amount or 95% alcoholic solution of 10% Tween 80 again, mixing is after aseptic filtration, filtrate adds 5 times of amount sterile distilled water mixings, in the sterile distilled water with 67 times 25 ℃ of this solution impourings, stirring makes solution clarification back place half an hour, filter through sintered filter funnel, drain, the distilled water wash of the about 10 times of amounts of reuse is repeatedly drained after the aseptic subpackaged artesunate crystallite that makes adds basifier and is dissolved into injection when to be used.
2, the preparation method of antimalarial artemisia apiacea ester for injection according to claim 1, wherein said basifier is with NaHCO
3Be advisable.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN85108105A CN1019266B (en) | 1985-10-17 | 1985-10-17 | Preparation of artemisia apiacea ester for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN85108105A CN1019266B (en) | 1985-10-17 | 1985-10-17 | Preparation of artemisia apiacea ester for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85108105A CN85108105A (en) | 1987-04-22 |
| CN1019266B true CN1019266B (en) | 1992-12-02 |
Family
ID=4795906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN85108105A Expired CN1019266B (en) | 1985-10-17 | 1985-10-17 | Preparation of artemisia apiacea ester for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1019266B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000044333A2 (en) * | 1999-01-28 | 2000-08-03 | Dinesh Shantilal Patel | Novel injectable antimalarial compositions of artemisinin |
| CN103169663A (en) * | 2011-12-26 | 2013-06-26 | 桂林南药股份有限公司 | Preparation method of ultrafine artesunate sterile powder |
-
1985
- 1985-10-17 CN CN85108105A patent/CN1019266B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CN85108105A (en) | 1987-04-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C13 | Decision | ||
| GR02 | Examined patent application | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |