CN103040842B - Prostaglandin pharmaceutical composition and prostaglandin medicament suppository prepared by the prostaglandin pharmaceutical composition - Google Patents
Prostaglandin pharmaceutical composition and prostaglandin medicament suppository prepared by the prostaglandin pharmaceutical composition Download PDFInfo
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- CN103040842B CN103040842B CN201210535400.3A CN201210535400A CN103040842B CN 103040842 B CN103040842 B CN 103040842B CN 201210535400 A CN201210535400 A CN 201210535400A CN 103040842 B CN103040842 B CN 103040842B
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Abstract
The invention discloses a prostaglandin pharmaceutical composition, containing 1 part by weight of prostaglandin medicament, and 1-300000 parts by weight of fat, wherein the fat is a mixture selected from one or more of cocoa butter, semisynthetic cocounut oil ester, semisynthetic litsea cubeba fat, mixed fatty glyceride, semisynthetic palm oil ester, propylene glycol stearate and lanolin. The technology effects of the invention reside in that: the misoprostol is catalyzed by water for degrading; the auxiliary material, of common preparation is hydrophilic, the fat is used as an auxiliary material, which greatly reduces the probability for the misoprostol to contact water, achieves unexpected effects, and significantly raises the stability in a storage period.
Description
Technical field
The present invention relates to a kind of compositions of stable prostaglandins pharmaceutical composition, particularly misoprostol-hydroxypropyl methylcellulose.
Background technology
The Yuan Yan producer of misoprostol is U.S. Searle company, be at first as antiulcerative exploitation and in 1985 first in Switzerland's listing, in the state such as American-European, Japanese, go on the market subsequently.This medicine is a kind of synthetic prostatitis element E1 analog, the same with similar drugs carboprost methylate, dinoprostone, owing to thering is the cervix maturation of promotion and strengthening uterine contraction effect, low dosage (25-50 μ g) is usually used in full-term pregnancy induced labor clinically, and high dose (200-1000 μ g) is for prevention, treatment postpartum hemorrhage.
In Egyptian and Brazil, for term induced labor Vaginal Misoprostol sheet, have listing (the commodity Prostokos by name of Brazil's listing).The misoprostol tablets by LC-MS (trade name: Isovent, specification is respectively 100 μ g, 200 μ g and 600 μ g) that Bangladesh Square Pharmaceuticals company produces, for prevention, treatment postpartum hemorrhage.This tablet is in the approval listing of 2008 Nian Bei Nepal.The domestic 200 μ g specification import sheets (commodity happiness by name gram feedback) that have Britain to produce, the 200 μ g specification misoprostol tablets by LC-MSs that Beijing black bamboo Pharmaceutical is produced.
Misoprostol is oily liquids under room temperature state, and chemical property is extremely unstable, needs 5 ° of C to fill below under nitrogen drying condition and preserves.U.S. Patent number 4,301,146 have described the dispersant of the solid state of misoprostol and polyvinylpyrrolidone (PVP) or hydroxypropyl emthylcellulose (HPMC).This technology has improved the stability of misoprostol, and it can deposited 2 years without filling under 2-8 ° of C air-proof condition of nitrogen.Misoprostol-hydroxypropyl emthylcellulose can be commercially available.
But because the degraded of misoprostol carrys out catalysis by water, polyvinylpyrrolidone or hydroxypropyl emthylcellulose all contain certain moisture and have certain hydrophilic, cannot accomplish to preserve for a long time under room temperature (15-25 ° of C) condition.
Summary of the invention
The object of the invention is in order to overcome misoprostol unstable easy degraded in preparation process, and the technological deficiency of the problem such as long-term lay up period catabolite showed increased, the preparation that a kind of preparation nature is stable is provided, provide a kind of simple, efficient technique of preparing this stable in properties preparation, to be applicable to industrialized great production simultaneously.
The technical solution used in the present invention is:
A prostaglandins pharmaceutical composition, described prostaglandins pharmaceutical composition comprises the prostaglandins medicine of 1 mass parts, the oils and fats of 1 to 300000 mass parts.
Preferred described prostaglandins pharmaceutical composition comprises the prostaglandins medicine of 1 mass parts, the oils and fats of 1000 to 50000 mass parts.
The meaning comprising of the present invention refers to that prostaglandins pharmaceutical composition can also contain other effect of the present invention is not had to the acceptable pharmaceutic adjuvant of influential other human bodies.
Oils and fats of the present invention is one or more the mixing in cocoa butter, semi-synthetic cocos nucifera oil ester, semi-synthetic Fructus Litseae grease, mixed fatty glycerides, semi-synthetic Petiolus Trachycarpi grease, propylene glycol stearate, lanoline, is preferably mixing of mixed fatty glycerides or mixed fatty glycerides and lanoline.
Prostaglandins medicine of the present invention can add in the mode of misoprostol-hydroxypropyl emthylcellulose, and the quality of described prostaglandins medicine is measured with the quality of misoprostol in misoprostol-hydroxypropyl emthylcellulose.Certainly each dosage form of other various prostaglandins medicine product can add, and with the quality of the pure prostaglandins medicine that wherein contains, measures ratio of component.
The present invention can stablize any stable compound, particularly its character person similar to misoprostol for medicine.
Described misoprostol-hydroxypropyl emthylcellulose can be commercially available, and in the alcohol-hydroxypropyl emthylcellulose of described prostatitis, misoprostol is 1 to 99 with the mass ratio of hydroxypropyl methylcellulose.
Further, the preferred described prostaglandins pharmaceutical composition of the present invention is by the misoprostol-hydroxypropyl emthylcellulose of 1 mass parts, the composition of 10 to 500 mass parts, more preferably by the misoprostol-hydroxypropyl emthylcellulose of 1 mass parts, the composition of 14 to 199 mass parts.
Prostaglandins pharmaceutical composition of the present invention can be made into prostaglandins drug suppository, and described prostaglandins drug suppository can make by the following method:
Oils and fats is heated to molten condition (being conventionally heated to 35 ~ 60 ℃), then under stirring, be cooled to 30-50 ℃, add by ratio of component and add prostaglandins medicine, after being uniformly mixed, according to the conversion of prescription ratio, control suppository weight and fill with mould, then cooling forming.
Technique effect of the present invention is mainly reflected in:
1, the degraded of misoprostol carrys out catalysis by water, the adjuvant of ordinary preparation all has certain hydrophilic, the present invention adopts oils and fats as adjuvant, has greatly reduced the probability that misoprostol touches water, obtain beyond thought effect, significantly improved the stability of this product at lay up period.
2, technique simple, saved a large amount of human and material resources.
3, this product is small dose drug, can be by controlling suppository quality, regulate active drug (being prostaglandins medicine) content in every suppository at 0.025mg between 0.6mg, medicine can be evenly distributed in oils and fats under stirring, fill with after mould cooling forming immediately, uniformity of dosage units is better than dry powder blend, and the less advantage of dosage is more obvious.
The specific embodiment
By specific embodiment given below, can further know that the present invention will be described, but they not limitation of the invention.
Misoprostol-hydroxypropyl methylcellulose in the embodiment of the present invention is by YONSUNG FINE CHEMICALS Co., LTD. buy and obtain, import drugs registration certificate H20100292, in misoprostol-hydroxypropyl methylcellulose, misoprostol is 1 to 99 with the mass ratio of hydroxypropyl methylcellulose.
Embodiment 1:
The present embodiment is the stable composition of a kind of misoprostol-hydroxypropyl methylcellulose of preparation and mixed fatty glycerides 34 types, by misoprostol-hydroxypropyl methylcellulose and mixed fatty glycerides 34 types, with mass ratio 1:14 ratio, is made.
First the mixed fatty glycerides of 11200 g, 34 types are placed in to material-compound tank, heated and stirred, to all meltings, is controlled heating-up temperature at 60 ℃.Again the substrate of melting is cooled to 38 ℃ under stirring, then 800g misoprostol-hydroxypropyl methylcellulose is dropped in material-compound tank, stir 15-30 min.In whipping process, control temperature of charge and be not less than 35 ℃.When material-compound tank temperature drops to 35 ℃, limit constant temperature stirs limit and fills with mould, controls the heavy 0.6g(scope of suppository 0.57-0.63g) cooling aftershaping.
Embodiment 2:
Step manufacture according to embodiment 1, the present embodiment is also the stable composition for the preparation of a kind of misoprostol-hydroxypropyl methylcellulose and mixed fatty glycerides 34 types, by misoprostol-hydroxypropyl methylcellulose and mixed fatty glycerides 34 types, with mass ratio 1:199 ratio, made, preparation method step is with embodiment 1.
Embodiment 3:
Step manufacture according to embodiment 1, the present embodiment is the stable composition for the preparation of a kind of misoprostol and mixed fatty glycerides 34 types, by misoprostol and mixed fatty glycerides 34 types, with mass ratio 1:1600 ratio, made, preparation method step is with embodiment 1.
Embodiment 4:
The present embodiment is the stable composition of preparation a kind of misoprostol-hydroxypropyl methylcellulose, mixed fatty glycerides 36 types and lanoline, by misoprostol-hydroxypropyl methylcellulose, mixed fatty glycerides 36 types and lanoline, with mass ratio 6:80:4 ratio, is made.
First 79.8g mixed fatty glycerides 36 types and 4.2g lanoline are placed in to material-compound tank, heated and stirred, to all meltings, is controlled heating-up temperature at 60 ℃.Again the substrate of melting is cooled to 38 ℃ under stirring, then 6.0g misoprostol-hydroxypropyl methylcellulose is dropped in material-compound tank, stir 15-30 min.In whipping process, control temperature of charge and be not less than 37 ℃.When material-compound tank temperature drops to 37 ℃, control the heavy 0.6g(scope of suppository 0.57-0.63g) limit constant temperature stirring limit filling mould, cooling aftershaping.
Comparative example 1:
By misoprostol-hydroxypropyl methylcellulose and hydrophilic matrix poloxamer, lactose, polyethylene glycol 6000 in mass ratio 6:30:62:2 mix rear compressingly, investigate its stability.
Stability test:
Embodiment 1 ~ 4 is made oils and fats matrix formulations and the preparation of the hydrophilic matrix that makes of comparative example 1 with being placed on 30 ℃, lower 1 month of RH65% condition, by high performance liquid chromatograph method, measure impurity situation of change, according to national import drugs registered standard (standard No.: JX20090357) measure, the results are shown in table one.Result shows that the oils and fats matrix formulations preservation character of embodiment 1 ~ 4 is more stable.
Commercially available misoprostol import sheet (trade name: happiness gram feedback) and embodiment 1 are made oils and fats matrix formulations with being placed on 45 ℃, lower 3 days of RH75% condition, by high performance liquid chromatograph method, measure impurity situation of change, according to national import drugs registered standard (standard No.: JX20090357) measure, the results are shown in table two.Result shows that the oils and fats matrix formulations preservation character of embodiment 1 is more stable.
The fat-based quality sample of embodiment 1 is placed on to 30 ℃, under RH65% condition, tests its long-term stability of preserving, 3 months testing times, impurity situation of change is as table three, and visible oils and fats substrate preparation stability is splendid, can be used for preserving for a long time medicine.
Table one
Table two
Table three
Claims (3)
1. a prostaglandins pharmaceutical composition, is characterized in that described prostaglandins pharmaceutical composition is by the misoprostol-hydroxypropyl emthylcellulose of 1 mass parts, the composition of 10 to 500 mass parts; In described misoprostol-hydroxypropyl emthylcellulose, misoprostol is 1 to 99 with the mass ratio of hydroxypropyl methylcellulose; Described oils and fats is mixed fatty glycerides or mixed fatty glycerides and the mixing of lanoline.
2. the prostaglandins drug suppository that prostaglandins pharmaceutical composition as claimed in claim 1 is made.
3. prostaglandins drug suppository as claimed in claim 2, is characterized in that described prostaglandins drug suppository makes by the following method:
Oils and fats is heated to molten condition, under then stirring, is cooled to 30-50 ℃, add by ratio of component and add prostaglandins medicine, after being uniformly mixed, according to the conversion of prescription ratio, controlling suppository weight and fill with mould, then cooling forming.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210535400.3A CN103040842B (en) | 2012-12-08 | 2012-12-08 | Prostaglandin pharmaceutical composition and prostaglandin medicament suppository prepared by the prostaglandin pharmaceutical composition |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210535400.3A CN103040842B (en) | 2012-12-08 | 2012-12-08 | Prostaglandin pharmaceutical composition and prostaglandin medicament suppository prepared by the prostaglandin pharmaceutical composition |
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| CN103040842A CN103040842A (en) | 2013-04-17 |
| CN103040842B true CN103040842B (en) | 2014-11-12 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20160008310A1 (en) | 2014-07-11 | 2016-01-14 | Azanta A/S | Misoprostol dispersible tablet |
| EP3166597A2 (en) | 2014-07-11 | 2017-05-17 | Azanta Danmark A/S | Misoprostol dispersible tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1939308A (en) * | 2005-09-28 | 2007-04-04 | 应圣俊 | Misoalprostacol suppository |
| CN102697746A (en) * | 2012-06-11 | 2012-10-03 | 广州朗圣药业有限公司 | Rapid melting misoprostol vaginal composition as well as preparation method and application of same |
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- 2012-12-08 CN CN201210535400.3A patent/CN103040842B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1939308A (en) * | 2005-09-28 | 2007-04-04 | 应圣俊 | Misoalprostacol suppository |
| CN102697746A (en) * | 2012-06-11 | 2012-10-03 | 广州朗圣药业有限公司 | Rapid melting misoprostol vaginal composition as well as preparation method and application of same |
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