CN1199612A - Preparation of new-type antimalarial drug artemisin methyl ether capsule - Google Patents
Preparation of new-type antimalarial drug artemisin methyl ether capsule Download PDFInfo
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- CN1199612A CN1199612A CN 97112062 CN97112062A CN1199612A CN 1199612 A CN1199612 A CN 1199612A CN 97112062 CN97112062 CN 97112062 CN 97112062 A CN97112062 A CN 97112062A CN 1199612 A CN1199612 A CN 1199612A
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- artemether
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Abstract
The present invention uses vegetable oil as oil solvent of medicinal material artemether in preparing the oily artemether capsule, and this makes the artemether medicine stable during storage and use and high in biological availability.
Description
The present invention relates to a kind of preparation method of new-type antimalarial drug artemisin methyl ether capsule, Artemether is artemisinin derivative, belong to methyl dihydroartemisinine β body, code name 8m 224, it is a kind of high-efficiency low-toxicity antimalarial of contemporary China, plasmodium schizont (phorozoon gonophore in the born of the same parents) there is stronger killing action, evident in efficacy for multiple resistant malaria and anti-chloroquine pernicious malaria.
But because Artemether is extremely responsive to light, temperature, humidity and oxygen, is easy to dehydrogenation and resolves into dihydroartemisinine, reduced the effective ingredient of Artemether and influence clinical efficacy.Therefore, in making the operation of Artemether tablet, because the exposed property of Artemether crude drug, be subject to the influence of light, heat, wet and oxygen, the tablet of making is stable inadequately at room temperature, is easy to decompose, and is difficult to store and influence is taken.Put under the room temperature according to evidence Artemether tablet, promptly begin soon to decompose, place after 1 year, its active constituent content descends about 5%.Therefore, only be fit to make injection or hard capsule, and the injection use needs certain medical condition, hard capsule needs baking at process for making, and is unfavorable to the effective ingredient of product.
The preparation method that the present invention proposes the Artemether soft gelatin capsule is to utilize Artemether to have oil-soluble characteristics, adopt factice ball manufacturing process, promptly in advance Artemether crude drug cold cut (can be selected from the multiple eating vegetable oil and used as olive oil, Oleum Helianthi, Oleum Arachidis hypogaeae semen and Oleum Glycines etc.) in Vegetable oil lipoprotein, after the oils and fats dissolution process, make Artemether factice ball.Its principle be the Artemether medicine by cold cut in oils and fats, it is in the airtight soft gelatin capsule for a long time, crude drug is not subjected to or is subjected to less the influence of external environment, weather conditions etc., lucifuge, keep away wet, keep away under the oxygen condition, guaranteed the Artemether components unchanged, its purpose be to have solved reliably the Artemether medicine make, store and sell use in unstability and rotten problem.Artemether soft gelatin capsule absorbability is good simultaneously, has improved its bioavailability significantly.
Technical essential of the present invention is the edible soybean oil that utilizes in the edible vegetable oil, makes Artemether factice ball with the Oleum Glycines cold cut Artemether crude drug that purification process is crossed, and this kind preparation is not seen the bibliographical information mistake as yet.
The edible vegetable oil and fat that the present invention proposes also can be used as the arteether in the artemisinin derivative or the oily molten adjuvant of artemisic succinate material medicine, makes arteether or artemisic succinate factice ball, and effect is identical.
Artemether factice ball that the present invention makes and the tablet contrast test made from batch crude drug are exposed to respectively under the room temperature, last the stability of 2 years effect of artemether, and the result shows that the stability of Artemether soft gelatin capsule obviously is better than the Artemether tablet.
The technical scheme embodiment that the present invention provides is as follows:
Embodiment 1: oily molten artemisinin derivatives (Artemether, arteether, artemisic succinate etc.) is as the quality standard of Artemether soft gelatin capsule
This product contains Artemether (C
16H
26O
5) should be the 90.0-110.0% of standard, include the yellow transparent oily liquids.
Source, the prescription of the Artemether molten adjuvant of oil (Oleum Glycines, Oleum Arachidis hypogaeae semen, Oleum sesami, Oleum Helianthi).For example: Oleum Glycines, should there be lot number in factory, should meet the Chinese Pharmacopoeia standard.Oleum Glycines should be the cold-press method vegetable fatty oil processing and refining that squeezes out and getting.
The Oleum Glycines character, faint yellow supernatant liquid has the faint scent, lightly seasoned of similar Semen Glycines seed, should not have foreign odor, and no tapinoma-odour, color and luster must not be deeper than yellow No. 6 standard color solutions (57 pages of two appendix of Chinese Pharmacopoeia nineteen ninety version).Should keep clear and bright in the time of 10 ℃, slightly soluble in ethanol can mix arbitrarily with ether, chloroform or petroleum ether.
Proportion: in the time of 20 ℃, be 0.911-0.918
Index of refraction: 1.469-1.472
Iodine number: 79-128
Saponification number: 185-200
Acid number: be not more than 0.56
The blank trap of ultraviolet: precision is measured this product 1ml, measures according to Artemether soft gelatin capsule determination, and its trap is 0.010-0.020.
Differentiate: getting this product is 26-32 ℃ according to the condensation point that the algoscopy of fatty acid condensation point under fat and the fatty oil method of inspection item should record fatty acid.
Check: heat run: get oil sample 50ml according to the test of pharmacopeia method, the color of observing oil, the increase of color number must not exceed secondary.
Embodiment 2: the prescription of Artemether factice pill
Artemether 200g
Edible soybean oil 1000g
Embodiment 3: the preparation technology of factice ball
(1) preparation of glue
1. get the water of 1.2 times of gelatin amounts and the glycerol of glue total amount 25-30%
2. be heated to 70-80 ℃ of mix homogeneously
3. adding gelatin stirs
4. fusion
5. leave standstill insulation 2 hours, Dai Pao Droplets come-up back scumming
6. filter: be incubated standby
(2) medicinal liquid preparation
1. get the Artemether crude drug and cross 40 order nylon mesh
2. add Oleum Glycines by proportioning
3. stirring and dissolving under the room temperature
4. treating to dissolve fully the back filters standby with the G1 sintered filter funnel.
(3) compacting of soft gelatin capsule
1. make film after the glue deaeration
2. oven dry
3. the Artemether medicinal liquid is quantitatively injected in the cooling back
4. make soft gelatin capsule with homemade pellet press, every seed lac ball charging is 250mg (including Artemether 40mg).
(4) drying of soft gelatin capsule
At the 20-30% relative humidity, carry out drying under the temperature 21-24 ℃ of air blast condition, glue shell water content is used the polishing of a small amount of wax powder at last in the 6-10% scope.
(5) soft gelatin capsule packing
Pack 12 of every plates, every box 2 plates with homemade Aluminium-coating Packer.
Embodiment 4: Artemether factice ball assay:
(1) assay method
The contents mixed of 1. getting under the content uniformity item is even;
2. precision takes by weighing in right amount (being equivalent to Artemether 60mg);
3. put in the 100ml measuring bottle, an amount of as dehydrated alcohol; Jolting, and be diluted to scale, shaking up, precision is measured 1ml, puts in the 50ml measuring bottle;
4. add hydrochloric acid ethanol solution (hydrochloric acid 90ml+ dehydrated alcohol is to 1000ml) to scale;
5. shake up close plug, with 55+1 ℃ of water bath with thermostatic control insulation 5 hours;
6. take out and be cooled to room temperature:
7. make blank with the hydrochloric acid ethanol solution;
8. use spectrophotometer to measure trap at 254 ± 1nm wavelength place, press C
16H
26O
5Absorptance E
1cmBe 379 calculating, promptly.
Embodiment 5: the Artemether preparation stability is measured
Stability with thin layer chromatography-hydrolysis-determined by ultraviolet spectrophotometry Artemether oil solution.After the flaggy chromatography, Artemether, dihydroartemisinine and oily three are separated, take off the Artemether speckle then, through acid hydrolysis, make Artemether present ultraviolet absorption peak, thereby with determined by ultraviolet spectrophotometry Artemether content, with proof stable case of Artemether soft gelatin capsule under difference placement condition, experimental result shows that 2 years effect duration of Artemether soft gelatin capsule are fully qualified.
Embodiment 6: Artemether factice pill is imitated and is observed
(1) the Mus malaria test of pesticide effectiveness
With K173 strain of Bai Shi Mus plasmodium and the in vivo test of anti-chloroquine strain white mice,, Artemether Semen arachidis hypogaeae oral with the Artemether aqueous suspensions by international test method is contrast by the liquid intramuscular injection, parallel contrast test is tired parasite killing speed and curative effect with the oral malaria of effect of artemether Oleum Glycines liquid.
(2) the monkey malaria test of pesticide effectiveness
Compare observation of curative effect so that the parallel relatively Artemether Oleum Glycines of Plasmodium knowlesi-Rhesus Macacus in vivo test liquid is oral with the intramuscular injection of Artemether Oleum Arachidis hypogaeae semen.
(3) to people's plasmodium observation in vitro:
Test is to the sensitivity of Artemether in the people Plasmodium falciparum In vitro culture.
Embodiment 7: Artemether factice ball toxicity test
With the white mice is object, carries out the different approaches administration of the oral and intramuscular injection of Artemether Oleum Glycines liquid, carries out acute toxicity and observes, use the Oleum Arachidis hypogaeae semen intramuscular administration simultaneously, as parallel control, observation is 14 days behind the medicine, the result of record the weight of animals, death condition and poisoning symptom etc.
Administration postmortem organ disease situation and the pathologic sampling check that animal and living was deposited behind the Mus medicine 14 days that cause death.
Claims (5)
1. the preparation method of a new-type antimalarial drug artemisin methyl ether capsule comprising the oily molten adjuvant that utilizes the various plants oils and fats as Artemether or arteether or artemisic succinate crude drug, is characterized in that utilizing the oily molten adjuvant of multiple eating vegetable oil as material medicine,
2. a kind of preparation method of new-type antimalarial drug artemisin methyl ether capsule according to claim 1 is characterized in that utilizing Oleum Glycines in the edible vegetable oil and fat, Oleum Helianthi, Oleum Arachidis hypogaeae semen, the Oleum sesami oily molten adjuvant as material medicine,
3. a kind of according to claim 1 preparation method of new antimalarial agent Artemether factice ball is characterized in that the Oleum Glycines proportion relation is Artemether 80 grams-250 grams in Artemether crude drug and the edible vegetable oil, Oleum Glycines 1000 grams,
4. the preparation method of a kind of according to claim 1 new antimalarial agent Artemether storage soft gelatin capsule, it is characterized in that being dissolved in the every ball of making in edible soybean oil or Oleum Arachidis hypogaeae semen or the Oleum Helianthi of factice ball fully by the Artemether crude drug, to contain Artemether be 40 milligrams to 20 milligrams,
5. a kind of according to claim 1 preparation method of new antimalarial agent Artemether factice ball is characterized in that Artemether or arteether or artemisic succinate crude drug are by Oleum Glycines or Oleum Arachidis hypogaeae semen or the sunflower seed oil immersion is molten is embedded in the airtight soft gelatin capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 97112062 CN1199612A (en) | 1997-05-16 | 1997-05-16 | Preparation of new-type antimalarial drug artemisin methyl ether capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 97112062 CN1199612A (en) | 1997-05-16 | 1997-05-16 | Preparation of new-type antimalarial drug artemisin methyl ether capsule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1199612A true CN1199612A (en) | 1998-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 97112062 Pending CN1199612A (en) | 1997-05-16 | 1997-05-16 | Preparation of new-type antimalarial drug artemisin methyl ether capsule |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105699584A (en) * | 2016-02-03 | 2016-06-22 | 昆药集团股份有限公司 | Detection method for artemether related matters |
| CN109663513A (en) * | 2018-05-10 | 2019-04-23 | 海南医学院 | A kind of preparation method and applications of Artemether lysate |
| CN109666621A (en) * | 2018-05-10 | 2019-04-23 | 海南医学院 | A kind of cell culture medium suspension finish of Artemether and its application in cell culture medium |
-
1997
- 1997-05-16 CN CN 97112062 patent/CN1199612A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105699584A (en) * | 2016-02-03 | 2016-06-22 | 昆药集团股份有限公司 | Detection method for artemether related matters |
| CN105699584B (en) * | 2016-02-03 | 2018-02-09 | 昆药集团股份有限公司 | A kind of detection method of Artemether related substances |
| CN109663513A (en) * | 2018-05-10 | 2019-04-23 | 海南医学院 | A kind of preparation method and applications of Artemether lysate |
| CN109666621A (en) * | 2018-05-10 | 2019-04-23 | 海南医学院 | A kind of cell culture medium suspension finish of Artemether and its application in cell culture medium |
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