CN101671382A - Ultra-micronized megestrol acetate and pharmaceutical composition containing same - Google Patents
Ultra-micronized megestrol acetate and pharmaceutical composition containing same Download PDFInfo
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- CN101671382A CN101671382A CN200910204082A CN200910204082A CN101671382A CN 101671382 A CN101671382 A CN 101671382A CN 200910204082 A CN200910204082 A CN 200910204082A CN 200910204082 A CN200910204082 A CN 200910204082A CN 101671382 A CN101671382 A CN 101671382A
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- pharmaceutical composition
- megestrol acetate
- micronized megestrol
- micronized
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Abstract
The invention relates to an ultra-micronized megestrol acetate in which 100% of particle sizes are smaller than or equal to 10 mu m. The invention also relates to a pharmaceutical composition containing the ultra-micronized megestrol acetate, which comprises an effective quantity of ultra-micronized megestrol acetate and medically acceptable excipient, wherein the effective quantity is 80-160 mg of ultra-micronized megestrol acetate. The pharmaceutical composition can be prepared into dispersing tablets, common tablets and capsules and used for treating advanced breast cancer, advanced endometrial carcinoma, renal carcinoma, prostatic cancer and oophoroma, and can improve the appetite and the cachexia of patients with advanced tumors.
Description
Technical field
The invention belongs to pharmaceutical field, be specifically related to ultra-micronized megestrol acetate and contain the pharmaceutical composition of ultra-micronized megestrol acetate.
Background technology
Magace is a kind of progestogen, be mainly used in the treatment advanced breast cancer and late period carcinoma of endometrium, kidney, prostate cancer and ovarian cancer are also had certain curative effect.And can improve the appetite and the emaciation of late tumor patient.
Because Magace is water insoluble, and the Chang Zuowei oral preparation drug administration, so its crystalline form and granularity be the important factor that influences drug bioavailability, directly influences curative effect of medication.Domestic commercially available Magace preparation mainly contains ordinary tablet, dispersible tablet and capsule etc. at present, the granularity of contained Magace raw material is 100 orders～120 orders, is equivalent to 150 μ m～125 μ m, and granularity is bigger, therefore absorption is slower, and bioavailability is lower.
The problems referred to above are not resolved as yet at home at present.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of ultra-micronized megestrol acetate is provided, it absorbs rapidly, and onset time is fast, and bioavailability is higher.
Another object of the present invention is to provide a kind of composition that contains ultra-micronized megestrol acetate.
According to an aspect of the present invention, provide a kind of ultra-micronized megestrol acetate.The present invention has carried out a large amount of tests; by Magace particle or meal are carried out grinding and processing; the strict control of Dichlorodiphenyl Acetate megestrol granularity; the Magace that final selection has appropriate particle size; obtain the Magace fine powder of homogeneous grain diameter, and make the preparation of this medicine have higher bioavailability and better therapeutic.
Ultra-micronized megestrol acetate of the present invention, its particle diameter of 100% is smaller or equal to 10 μ m; Preferably, its particle diameter of 90～100% is smaller or equal to 5 μ m.
According to a further aspect in the invention, provide the pharmaceutical composition that contains ultra-micronized megestrol acetate, it comprises the ultra-micronized megestrol acetate and the pharmaceutically acceptable vehicle of significant quantity.Wherein, the content of the ultra-micronized megestrol acetate of described significant quantity is 80-160mg, the heavy 160-340mg of per unit preparation, and described pharmaceutically acceptable vehicle can comprise thinner, disintegrating agent and lubricant.
Thinner of the present invention, disintegrating agent and lubricant can be the pharmaceutically conventional materials that uses, and described thinner is selected from starch, dextrin, Microcrystalline Cellulose, sucrose, lactose etc., preferably uses Microcrystalline Cellulose; Described disintegrating agent is selected from sodium starch glycolate, low-substituted hydroxypropyl methylcellulose, polyvinylpyrrolidone etc., preferentially uses polyvinylpyrrolidone; Described lubricant is a Magnesium Stearate.
In first kind of embodiment, described pharmaceutical composition comprises the component of following weight proportion: Magace: thinner: disintegrating agent: lubricant=(300-320): (100-120): (150-180): (2-4).
In second kind of embodiment, described pharmaceutical composition comprises the component of following weight proportion: Magace: thinner: disintegrating agent: lubricant=(300-320): (200-250): (50-60): (2-4).
The pharmaceutical composition that contains ultra-micronized megestrol acetate of the present invention can be made into multiple formulation, especially is fit to make capsule or tablet, preferably makes dispersible tablet.For example, the pharmaceutical composition in first kind of embodiment can be made dispersible tablet, the pharmaceutical composition in second kind of embodiment is made ordinary tablet or capsule.It is 80-160mg that the ultra-micronized megestrol acetate capsule of unit formulation or tablet (one or a slice) contain effective composition total amount.
The method for preparing super-fine powder Magace of the present invention can be a conventional breaking method known in the art, comprises comminution by gas stream, ball mill pulverizing etc.
The method that preparation contains the pharmaceutical preparation of super-fine powder Magace can be according to conventional formulation method known in the art, and each component is mixed by proportioning, and granulation or compressing tablet form.
Ultra-micronized megestrol acetate of the present invention or the pharmaceutical composition that contains ultra-micronized megestrol acetate can be used for treating cancer, be particularly useful for treating advanced breast cancer and late period carcinoma of endometrium, kidney, prostate cancer and ovarian cancer also there are certain curative effect, and can improve the appetite and the emaciation of late tumor patient.
Embodiment
Further describe this explanation with example below, help the present invention and effect thereof, advantage are better understood, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1: the preparation of ultra-micronized megestrol acetate dispersible tablet
Prescription: ultra-micronized megestrol acetate 1.6kg
Microcrystalline Cellulose 0.5kg
Polyvinylpyrrolidone 1.0kg
Magnesium Stearate 0.02kg
Starch slurry is an amount of
Make 10000
The preparation method: Magace, Microcrystalline Cellulose, polyvinylpyrrolidone are pulverized with the jet mill grinding machine respectively, mixed, wherein the grain diameter of Magace 100% is smaller or equal to 10 μ m.Add the appropriate amount of starch slurry then in mixture, stir and granulate, oven dry, whole grain add Magnesium Stearate at last, and mixing is used the tabletting machine compressing tablet, obtains 10000 Magace dispersible tablets.
Embodiment 2: the preparation of ultra-micronized megestrol acetate sheet
Prescription: ultra-micronized megestrol acetate 1.6kg
Microcrystalline Cellulose 1.2kg
Polyvinylpyrrolidone 0.3kg
Magnesium Stearate 0.02kg
Starch slurry is an amount of
Make 10000
The preparation method: Magace, Microcrystalline Cellulose, polyvinylpyrrolidone are pulverized with the jet mill grinding machine respectively, mixed, wherein the grain diameter of Magace 100% is smaller or equal to 10 μ m.Add the appropriate amount of starch slurry then in mixture, stir and granulate, oven dry, whole grain add Magnesium Stearate at last, and mixing is used the tabletting machine compressing tablet, obtains 10000 Magace sheets.
Embodiment 3: the capsular preparation of ultra-micronized megestrol acetate
Prescription: ultra-micronized megestrol acetate 1.6kg
Microcrystalline Cellulose 1.2kg
Polyvinylpyrrolidone 0.3kg
Magnesium Stearate 0.02kg
Starch slurry is an amount of
Make 10000
The preparation method: Magace, Microcrystalline Cellulose, polyvinylpyrrolidone are pulverized with the jet mill grinding machine respectively, mixed, wherein the grain diameter of Magace 100% is smaller or equal to 10 μ m.Add the appropriate amount of starch slurry then in mixture, stir and granulate, oven dry, whole grain add Magnesium Stearate at last, and mixing is used the fully-automatic capsule filling machine filling, obtains 10000 Magace capsules.
Embodiment 4: the comparison of dissolution rate
Ultra-micronized megestrol acetate dispersible tablet of the present invention, ordinary tablet and capsule are carried out the dissolution rate comparison test of effective constituent respectively with commercially available Magace dispersible tablet, ordinary tablet and capsule, the results are shown in Table 1-3.Wherein:
Commercially available Magace dispersible tablet: Qingdao Gerui Pharmaceutical Co., Ltd. produces; Commercially available Magace sheet: Shanghai Sine Kangjie Pharmaceutical Co., Ltd. produces; Commercially available Magace capsule: beginning pharmaceutical Co. Ltd in Nanjing produces.
Table 1: Magace dispersible tablet dissolution rate relatively
Table 2: Magace tablet dissolution rate relatively
Table 3: Magace capsule dissolution rate relatively
From the table 1-3 as can be seen, the dissolution rate of effective constituent is obviously more higher than commercially available Magace dispersible tablet, ordinary tablet and capsule in the dispersible tablet that ultra-micronized megestrol acetate of the present invention is made, conventional tablet and the capsule, therefore Magace can be absorbed in human body quickly, thereby reaches purpose rapid-action, that bioavailability improves.
The comparison of embodiment 5 relative bioavailabilities
Ultra-micronized megestrol acetate dispersible tablet of the present invention (with embodiment 1), ordinary tablet (with embodiment 2) and capsule (with embodiment 3) are carried out the comparison test of relative bioavailability to 30 healthy volunteers with commercially available Magace dispersible tablet, ordinary tablet and capsule respectively under fasted conditions, to every group (n=5), commercially available dispersible tablet, ordinary tablet and the capsule of difference administration 160mg Magace and the composition of embodiment 1, embodiment 2 and embodiment 3, and carry out cross matching.The Plasma Concentration that obtains Magace thus is shown in table 4-6.The commercially available prod is identical with embodiment 4.
Table 4: the comparison of the Plasma Concentration of Magace in the Magace dispersible tablet
* C
MaxThe expression peak concentration
* AUC represents lower area of blood concentration-time curve
Table 5: the comparison of the Plasma Concentration of Magace in the Magace sheet
* C
MaxThe expression peak concentration
* AUC represents lower area of blood concentration-time curve
Table 6: the comparison of the Plasma Concentration of Magace in the Magace capsule
* C
MaxThe expression peak concentration
* AUC represents lower area of blood concentration-time curve
From the table 4-6 as can be seen, effective constituent is obviously more higher than commercially available Magace dispersible tablet, ordinary tablet and capsule in the Plasma Concentration of human body in the dispersible tablet that ultra-micronized megestrol acetate of the present invention is made, ordinary tablet and the capsule, and onset is obviously rapid, confirms that the pharmaceutical composition that contains ultra-micronized megestrol acetate of the present invention can reach to improve bioavailability, rapid-action purpose.
Claims (10)
1, a kind of ultra-micronized megestrol acetate is characterized in that, its particle of 100% footpath grain is smaller or equal to 10 μ m.
2, ultra-micronized megestrol acetate as claimed in claim 1 is characterized in that, the grain diameter of its 90%-100% is smaller or equal to 5 μ m.
3, a kind of pharmaceutical composition, it comprises the ultra-micronized megestrol acetate and the pharmaceutically acceptable vehicle of significant quantity.
4, pharmaceutical composition as claimed in claim 3 is characterized in that, the ultra-micronized megestrol acetate of described significant quantity is 80-160mg, the heavy 160-340mg of unit formulation.
5, pharmaceutical composition as claimed in claim 3 is characterized in that comprising following components in part by weight: ultra-micronized megestrol acetate: thinner: disintegrating agent: lubricant=(300-320): (100-120): (150-180): (2-4);
Wherein thinner is starch, dextrin, Microcrystalline Cellulose, sucrose or lactose; Disintegrating agent is sodium starch glycolate, low-substituted hydroxypropyl methylcellulose or polyvinylpyrrolidone; Lubricant is a Magnesium Stearate.
6, pharmaceutical composition as claimed in claim 3 is characterized in that comprising following components in part by weight: ultra-micronized megestrol acetate: thinner: disintegrating agent: lubricant=(300-320): (200-250): (50-60): (2-4);
Wherein thinner is starch, dextrin, Microcrystalline Cellulose, sucrose or lactose; Disintegrating agent is sodium starch glycolate, low-substituted hydroxypropyl methylcellulose or polyvinylpyrrolidone; Lubricant is a Magnesium Stearate.
As each described pharmaceutical composition of claim 5-6, it is characterized in that 7, described thinner is a Microcrystalline Cellulose.
As each described pharmaceutical composition of claim 5-6, it is characterized in that 8, described disintegrating agent is a polyvinylpyrrolidone.
As each described pharmaceutical composition of claim 3-6, it is characterized in that 9, described pharmaceutical composition can be prepared into and disperse sheet, ordinary tablet or capsule.
10, each described pharmaceutical composition of claim 3-6 is used for the treatment of application in the medicine of advanced breast cancer, late period carcinoma of endometrium, kidney, prostate cancer, ovarian cancer in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102040820A CN101671382B (en) | 2009-10-08 | 2009-10-08 | Ultra-micronized megestrol acetate and pharmaceutical composition containing same |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009102040820A CN101671382B (en) | 2009-10-08 | 2009-10-08 | Ultra-micronized megestrol acetate and pharmaceutical composition containing same |
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| Publication Number | Publication Date |
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| CN101671382A true CN101671382A (en) | 2010-03-17 |
| CN101671382B CN101671382B (en) | 2012-07-18 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104208072A (en) * | 2013-05-31 | 2014-12-17 | 上海星泰医药科技有限公司 | Megestrol acetate hot-melt extrusion preparation |
| CN106109435A (en) * | 2016-07-09 | 2016-11-16 | 南京臣功制药股份有限公司 | A kind of megestrol acetate capsule and preparation method thereof |
| CN106137993A (en) * | 2016-08-09 | 2016-11-23 | 南京臣功制药股份有限公司 | A kind of megestrol acetate dispersible tablet and preparation method thereof |
| CN108409821A (en) * | 2018-03-19 | 2018-08-17 | 青岛国海生物制药有限公司 | A kind of preparation method and megestrol acetate of megestrol acetate nanocrystal |
| CN111643463A (en) * | 2020-07-08 | 2020-09-11 | 西安远大德天药业股份有限公司 | Megestrol acetate dispersible tablet and preparation method thereof |
-
2009
- 2009-10-08 CN CN2009102040820A patent/CN101671382B/en active Active
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104208072A (en) * | 2013-05-31 | 2014-12-17 | 上海星泰医药科技有限公司 | Megestrol acetate hot-melt extrusion preparation |
| CN106109435A (en) * | 2016-07-09 | 2016-11-16 | 南京臣功制药股份有限公司 | A kind of megestrol acetate capsule and preparation method thereof |
| CN106109435B (en) * | 2016-07-09 | 2018-11-06 | 南京臣功制药股份有限公司 | A kind of megestrol acetate capsule and preparation method thereof |
| CN106137993A (en) * | 2016-08-09 | 2016-11-23 | 南京臣功制药股份有限公司 | A kind of megestrol acetate dispersible tablet and preparation method thereof |
| CN106137993B (en) * | 2016-08-09 | 2018-11-09 | 南京臣功制药股份有限公司 | A kind of megestrol acetate dispersible tablet and preparation method thereof |
| CN108409821A (en) * | 2018-03-19 | 2018-08-17 | 青岛国海生物制药有限公司 | A kind of preparation method and megestrol acetate of megestrol acetate nanocrystal |
| CN111643463A (en) * | 2020-07-08 | 2020-09-11 | 西安远大德天药业股份有限公司 | Megestrol acetate dispersible tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN101671382B (en) | 2012-07-18 |
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Owner name: QINGDAO GUOHAI BIOPHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: QINGDAO GERUI PHARMACEUTICAL CO., LTD. Effective date: 20120524 |
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Effective date of registration: 20120524 Address after: 266112, Chengyang District, Shandong City, Qingdao Province, Danyang Road, south side of the road Applicant after: Qingdao Guohai Biological Pharmaceutical Co., Ltd. Address before: 266108, Shandong District, Qingdao City, Chengyang Road, south end of dual Road Applicant before: Qingdao Gerui Pharmaceutical Co., Ltd. |
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