CN101480401A - Medroxyprogesterone acetate tablet and preparation method thereof - Google Patents
Medroxyprogesterone acetate tablet and preparation method thereof Download PDFInfo
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- CN101480401A CN101480401A CNA2008100009142A CN200810000914A CN101480401A CN 101480401 A CN101480401 A CN 101480401A CN A2008100009142 A CNA2008100009142 A CN A2008100009142A CN 200810000914 A CN200810000914 A CN 200810000914A CN 101480401 A CN101480401 A CN 101480401A
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Abstract
The invention relates to a medroxyprogesterone tablet which is medicine for treating cancer and a preparation method thereof. Each tablet contains 0.5g of medroxyprogesterone and a right amount of officinal ancillary materials which are selected from filling agents, binding agents, disintegrants and lubricating agents and contain 0.025g to 0.035g of lactose, 0.05g to 0.07g of carboxymethyl starch sodium, 0.005g to 0.02g of polyvinylpyrrolidone (PVP K-29/32), 0.002g to 0.004g of magnesium stearate and 0.1g to 0.3g of ethanol of 50 percent. The ancillary materials are sifted, mixed, pelletized and tableted to prepare the medroxyprogesterone tablet. The medroxyprogesterone tablet has outstanding advantages of good stability, curative effect for long term usage and tolerance, high solubility and safety, little untoward effect, and the like.
Description
Technical field
The present invention relates to a kind of medicine medroxyprogesterone acetate tablet for the treatment of cancer and preparation method thereof.
Background technology
Breast carcinoma, adenocarcinoma of endometrium are modal gynecologic malignant tumors, its standard treatment comprises operations such as mastectomy, panhysterectomy, but the treatment that keeps fertility and can't accept standard because of the high patient of internal medicine complication operation risk for needs, many researching and proposing, for neoplasm staging early, patient that cell differentiation is high can give the hormone expectant treatment.
Medroxyprogesterone acetate is as the endocrine therapy medicine of hormone-dependent tumors such as breast carcinoma, carcinoma of endometrium, and present wide clinical application also obtains satisfied effect.Simultaneously, medroxyprogesterone acetate as endocrine medicine list with or share treatment carcinoma of prostate, renal carcinoma with antitumor drug, prostatic adenoma also has the effect that improves curative effect.The chemotherapeutics of other treatment breast carcinoma, carcinoma of endometrium, carcinoma of prostate, renal carcinoma, prostatic adenoma has certain toxic and side effects, patient's body is produced injury, but the advantage of medroxyprogesterone acetate is not only can treat separately or Synergistic treatment, can also obviously improve the patient anorexia, lose weight and symptom such as cachexia, thereby improve patient's overall health of patients and quality of life.
Medroxyprogesterone acetate belongs to oral desogestrel class medicine, and being derived by progesterone forms.Exist methyl and 17 to exist the acetoxyl group except 6, this product has identical structure with natural progesterone.Medroxyprogesterone acetate has pregnancy hormone like-effect and estrogen antagonist and antigonadotropic effect.Under doses, medroxyprogesterone acetate can reach hormonal system simultaneously and play a role on cellular level.This product is used for the treatment of following disease: breast carcinoma, carcinoma of endometrium, carcinoma of prostate, renal carcinoma, prostatic adenoma.Specification: 0.5g.
Medroxyprogesterone acetate (Medroxyprogesterone Acetate), molecular formula: C
24H
34O
4, being the crystalline powder of white or off-white color, very easily dissolving is dissolved in acetone in chloroform, and is molten in the ethyl acetate part omitted, and slightly soluble in dehydrated alcohol is insoluble in water.After solid drugs was oral, dissolving could be absorbed by body earlier, therefore the absorption of solid preparation comprises a series of processes, and promptly at first disintegrate becomes small-particle, dissolving, by biomembrane, absorption enters blood circulation at last, and the speed of whole process depends on the process that its medium velocity is the slowest.Its process in leaching of the medicine of poorly water-soluble is often the slowest, becomes the limiting factor in the absorption process.In order to solve medroxyprogesterone acetate sheet dissolution problem, we have carried out a series of research work.If medicine is hydrophobic or indissoluble and adjuvant is hydrophilic or solvable, then can improve the disintegrate stripping of tablet.Its reason at first is to improve the hydrophilic of whole tablet, thereby after making aqueous medium can infiltrate tablet inside the disintegrate process in leaching takes place.So we select novel import adjuvant for use, at first use the hydrophilicity condiment lactose; Secondly the influence of kind, consumption and the adding method etc. of disintegrating agent also is conspicuous.The consumption of disintegrating agent is many more, and disintegrate is fast more; Disintegrating agent adds then disintegrate effect simultaneously inside and outside granule best, and not only disintegrate soon but also help stripping.We use carboxymethyl starch sodium as disintegrating agent, adopt inside and outside addition, have quickened rate of moisture absorption, have increased swellability, have increased the stripping of medicine.
Summary of the invention
The objective of the invention is to fill up the blank that domestic production enterprise does not have 0.5g specification medroxyprogesterone acetate sheet, for " Chinese pharmacopoeia provides the standard of 0.5g medroxyprogesterone acetate sheet, and provides more selection for clinical application.The present invention also alleviates the misery that the cancer patient repeatedly takes a large amount of small dimension medroxyprogesterone acetate sheets simultaneously, makes things convenient for clinical application.
Another object of the present invention provides and a kind ofly can increase medroxyprogesterone acetate sheet method of dissolution.
Medroxyprogesterone acetate sheet of the present invention, every contains medroxyprogesterone acetate 0.5 gram and proper quantity of medicinal auxiliary material.Pharmaceutic adjuvant is selected from filler, binding agent, disintegrating agent and lubricant.
Filler can adopt starch, dextrin, Icing Sugar, lactose, amylum pregelatinisatum, microcrystalline Cellulose, mannitol, calcium sulfate, calcium hydrogen phosphate, medicinal calcium carbonate.
Binding agent can adopt the aqueous solution of distilled water, ethanol, starch slurry, dextrin, arabic gum, gelatin, polyvinylpyrrolidone or alcoholic solution, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, hypromellose.
Disintegrating agent can adopt dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose.
Lubricant can adopt magnesium stearate, Pulvis Talci, micropowder silica gel, hydrogenated vegetable oil, month pure magnesium sulfate of extension, Polyethylene Glycol etc.
The present invention is mainly used in the production technology of treatment cancer drug medroxyprogesterone acetate sheet, it is characterized in that this method may further comprise the steps:
(1) get the raw materials ready: 1) the Dichlorodiphenyl Acetate medroxyprogesterone is crossed 80 mesh sieves, and lactose, carboxymethyl starch sodium are crossed 120 mesh sieves respectively.Take by weighing adjuvant respectively by the prescription specified volume, standby.2) polyvinylpyrrolidone (PVP K-29/32) with recipe quantity is dissolved in 50% ethanol, and it is molten entirely to be stirred to PVP K-29/32, and sealing is standby.
(2) mix: the medroxyprogesterone acetate after will sieving, lactose, carboxymethyl starch sodium are done and are mixed, and the time is 1 hour, carries out wet mixing with 50%PVP K-29/32 alcoholic solution as binding agent, and the time is 30 minutes.
(3) granulate: 1) mixed supplementary material is made qualified soft material; With the wet grain of 18 order nylon sieve series.2) grain that will wet divides pot to carry out drying, and temperature＜50 ℃ are about 6～8 hours drying time.3) dried granule is crossed 16 mesh sieves and carry out granulate.
(4) tabletting: with the carboxymethyl starch sodium mix homogeneously of dried granule and magnesium stearate, recipe quantity, punch die tabletting.This product is white compressed tablet.
Adjuvant of the present invention is all selected novel import adjuvant for use, and lactose is a filler, is a kind of economical adjuvant, has the formedness price ratio, and no hygroscopicity is mobile, compressibility is good, and stable in properties is with most drug chemically reactive not; Carboxymethyl starch sodium is as disintegrating agent, adopts inside and outside addition, and the disintegrate effect is best, and not only disintegrate soon but also help stripping; Make binding agent with 50%PVP K-29/32 alcoholic solution, granulate after the oven dry, mobility of particle is good, is lubricant with the magnesium stearate, and the tablet compressibility is good.The slice, thin piece any surface finish, color and luster is even, has certain degree of hardness.
The tablet that adjuvant that the present invention is selected and principal agent medroxyprogesterone acetate are made has good stability, and the dissolution height has life-time service good effect, safe, many outstanding advantages such as price is low, untoward reaction is little, better tolerance.
The specific embodiment
The present invention prepares as stated above, and its detailed component is provided by the following example, but protection model circle of the present invention is not limited to this.
| Embodiment 5 | Component | Amount (gram/sheet) |
| Medroxyprogesterone acetate | 0.5g | |
| Lactose | 0.03g | |
| Carboxymethyl starch sodium (in add) | 0.036g | |
| Carboxymethyl starch sodium (adding) | 0.024g | |
| PVP?K-29/32 | 0.01g | |
| Magnesium stearate | 0.003g | |
| Ethanol (50%) | 0.2g | |
| Sheet is heavy | 0.603g |
One, preparation method:
1, get the raw materials ready: 1) the Dichlorodiphenyl Acetate medroxyprogesterone is crossed 80 mesh sieves, and lactose, carboxymethyl starch sodium are crossed 120 mesh sieves respectively.Take by weighing adjuvant respectively by the prescription specified volume, standby.2) polyvinylpyrrolidone (PVP K-29/32) with recipe quantity is dissolved in 50% ethanol, and it is molten entirely to be stirred to PVP K-29/32, and sealing is standby.
2, mix: the medroxyprogesterone acetate after will sieving, lactose, carboxymethyl starch sodium are done and are mixed, and the time is 1 hour, carries out wet mixing with 50%PVP K-29/32 alcoholic solution as binding agent, and the time is 30 minutes.
3, granulate: 1) mixed supplementary material is made qualified soft material; With the wet grain of 18 order nylon sieve series.2) grain that will wet divides pot to carry out drying, and temperature＜50 ℃ are about 6～8 hours drying time.3) dried granule is crossed 16 mesh sieves and carry out granulate.
4, tabletting: with the carboxymethyl starch sodium mix homogeneously of dried granule and magnesium stearate, recipe quantity, punch die tabletting.This product is white compressed tablet.
Two, dissolution test
1, instrument and reagent
Instrument: ZRS-8G intellectual drug digestion instrument (Radio Factory of Tianjin Univ.)
Reagent: medroxyprogesterone acetate sheet
2, method: ultraviolet visible spectrophotometry
This product adopts ultraviolet visible spectrophotometry (2005 editions two appendix IVA of Chinese Pharmacopoeia) to measure content.
Detect wavelength: 242nm
Test parameters:
Dissolving-out method: second method (oar method)
Dissolution medium: 0.5% sodium dodecyl sulfate solution 900ml; Rotating speed: 100 rev/mins
Limit the quantity of: 〉=50% (45 minutes)
3, dissolution determination result
Get by three batches of the medroxyprogesterone acetate sheets of the foregoing description preparation and test, measurement result sees Table:
4, import sample dissolution determination:
The name of an article: medroxyprogesterone acetate sheet; Specification: 500mg/ sheet (Pfizer)
Carry out dissolution determination with similarity condition, measurement result such as following table:
This shows that the medroxyprogesterone acetate sheet of present embodiment preparation is compared with the import sample, has higher dissolution.
Three, stability test
To be positioned over according to the medroxyprogesterone acetate sheet of present embodiment preparation under 40 ℃, relative humidity (R.H.) 75% condition, investigate the situation of change of sample outward appearance, dissolution, related substance, content in the time of 0,1,2,3 month.See the following form.
Result of the test shows that under these conditions dissolution, related substance and content have no significant change.Product is more stable.
The medroxyprogesterone acetate sheet that the present invention is made is used for the observation of curative effect after the clinical treatment malignant tumor patient chemotherapy:
1, physical data: treatment is organized in 53 examples, male's 35 examples, women's 18 examples, 32～74 years old age, The median age 59 years old.Matched group 47 examples, male's 32 examples, women's 15 examples, 28～71 years old age, The median age 56 years old.In two groups, carcinoma of endometrium 29 examples, breast carcinoma 21 examples, gastric cancer 10 examples, malignant lymphoma 8 examples, colorectal cancer 6 examples, the esophageal carcinoma 5 examples, each 4 example of soft tissue sarcoma, tumor of head and neck and ovarian cancer, carcinoma of prostate 3 examples, cancer of pancreas, each 2 example of renal carcinoma, cancer of biliary duct, each 1 example of bladder cancer.
2, Therapeutic Method: treatment is organized weekly the phase chemotherapy and is given medroxyprogesterone acetate 500mg, every day 1 time, and PO, 5～10 days is a course of treatment.Matched group is not taken any ancillary drug.
3, result: treatment organized for 53 routine 130 cycles of chemotherapy, and in 47 routine 112 cycles of chemotherapy of matched group, treatment group curative effect after the chemotherapy: produce effects 38 examples account for 717%; Effective 11 examples account for 208%; Invalid 4 examples account for 75%.Total effective rate (produce effects+effectively) account for 925% (49/53).Do not give any treatment behind the matched group chemotherapy of patients, appetite is recovered, and passes judgment on by the treatment standard, and produce effects 9 examples account for 191%; Effective 7 examples account for 149%.Invalid 31 examples account for 660%; Total effective rate (produce effects+effectively) account for 340% (16/47).Two groups relatively have significant difference (P＜005).Curative effect and peripheral blood cells change see Table 1, table 2.
Observation of curative effect behind the oral MPA of table 1 chemotherapy patients
Peripheral hemogram changes behind the oral MPA of table 2 chemotherapy patients
Medroxyprogesterone acetate as endocrine medicine list with or share treatment breast carcinoma, carcinoma of endometrium, carcinoma of prostate, renal carcinoma etc. with antitumor drug, the effect that improves curative effect is arranged.And oral medroxyprogesterone acetate untoward reaction is low, and the improving appetite effect is fast, and taking convenience is to the treatment of tumour patient and improve patient and quality of life all play a part good.
Claims (9)
1, a kind of tablet for the treatment of cancer is characterized in that every in this tablet contains medroxyprogesterone acetate 0.5 gram and proper quantity of medicinal auxiliary material
2, tablet according to claim 1 is characterized in that above-mentioned pharmaceutic adjuvant is selected from filler, binding agent, disintegrating agent and lubricant.
3, tablet according to claim 2. it is characterized in that filler can adopt starch, dextrin, Icing Sugar, lactose, amylum pregelatinisatum, microcrystalline Cellulose, mannitol, calcium sulfate, calcium hydrogen phosphate, medicinal calcium carbonate.
4, tablet according to claim 2 is characterized in that binding agent can adopt the aqueous solution of distilled water, ethanol, starch slurry, dextrin, arabic gum, gelatin, polyvinylpyrrolidone or alcoholic solution, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, hypromellose.
5, tablet according to claim 2 is characterized in that disintegrating agent can adopt dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose.
6, tablet according to claim 2 is characterized in that lubricant can adopt magnesium stearate, Pulvis Talci, micropowder silica gel, hydrogenated vegetable oil, month pure magnesium sulfate of extension, Polyethylene Glycol etc.
7, a kind ofly prepare the method that contains the tablet of medroxyprogesterone acetate active ingredient as claimed in claim 1, it is characterized in that this method may further comprise the steps:
(1) get the raw materials ready: 1) the Dichlorodiphenyl Acetate medroxyprogesterone is crossed 80 mesh sieves, and lactose, carboxymethyl starch sodium are crossed 120 mesh sieves respectively.Take by weighing adjuvant respectively by the prescription specified volume, standby.2) polyvinylpyrrolidone (PVP K-29/32) with recipe quantity is dissolved in 50% ethanol, and it is molten entirely to be stirred to PVP K-29/32, and sealing is standby.
(2) mix: the medroxyprogesterone acetate after will sieving, lactose, carboxymethyl starch sodium are done and are mixed, and the time is 1 hour, carries out wet mixing with 50%PVP K-29/32 alcoholic solution as binding agent, and the time is 30 minutes.
(3) granulate: 1) mixed supplementary material is made qualified soft material; With the wet grain of 18 order nylon sieve series.2) grain that will wet divides pot to carry out drying, and temperature＜50 ℃ are about 6～8 hours drying time.3) dried granule is crossed 16 mesh sieves and carry out granulate.
(4) tabletting: with the carboxymethyl starch sodium mix homogeneously of dried granule and magnesium stearate, recipe quantity, punch die tabletting.
8, preparation method according to claim 7, it is characterized in that each constituent content is respectively in every in the described tablet: medroxyprogesterone acetate 0.5g, lactose 0.025-0.035g, carboxymethyl starch sodium 0.05-0.07g, polyvinylpyrrolidone (PVP K-29/32) 0.005-0.02g, magnesium stearate 0.002-0.004g, 50% ethanol 0.1-0.3g.
9, preparation method according to claim 8, it is characterized in that, each constituent content is respectively in every in the wherein said tablet: medroxyprogesterone acetate 0.5g, lactose 0.03g, carboxymethyl starch sodium 0.06g, polyvinylpyrrolidone (PVP K-29/32) 0.01g, magnesium stearate 0.003g, 50% ethanol 0.2g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100009142A CN101480401A (en) | 2008-01-08 | 2008-01-08 | Medroxyprogesterone acetate tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100009142A CN101480401A (en) | 2008-01-08 | 2008-01-08 | Medroxyprogesterone acetate tablet and preparation method thereof |
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| CN101480401A true CN101480401A (en) | 2009-07-15 |
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|---|---|---|---|
| CNA2008100009142A Pending CN101480401A (en) | 2008-01-08 | 2008-01-08 | Medroxyprogesterone acetate tablet and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103800299A (en) * | 2014-02-25 | 2014-05-21 | 刘艳青 | Medroxyprogesterone tablet and preparation process thereof |
| CN106994120A (en) * | 2016-01-22 | 2017-08-01 | 江苏恒瑞医药股份有限公司 | A kind of pharmaceutical composition containing bicycle substituted pyrazolone azo analog derivative or its salt and preparation method thereof |
| CN107028899A (en) * | 2016-02-04 | 2017-08-11 | 江苏恒瑞医药股份有限公司 | A kind of pharmaceutical composition containing pyridopyrimidines derivatives or its officinal salt |
-
2008
- 2008-01-08 CN CNA2008100009142A patent/CN101480401A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103800299A (en) * | 2014-02-25 | 2014-05-21 | 刘艳青 | Medroxyprogesterone tablet and preparation process thereof |
| CN106994120A (en) * | 2016-01-22 | 2017-08-01 | 江苏恒瑞医药股份有限公司 | A kind of pharmaceutical composition containing bicycle substituted pyrazolone azo analog derivative or its salt and preparation method thereof |
| CN106994120B (en) * | 2016-01-22 | 2021-05-14 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition containing bicyclo-substituted pyrazolone azo derivative or salt thereof and preparation method thereof |
| CN107028899A (en) * | 2016-02-04 | 2017-08-11 | 江苏恒瑞医药股份有限公司 | A kind of pharmaceutical composition containing pyridopyrimidines derivatives or its officinal salt |
| CN107028899B (en) * | 2016-02-04 | 2021-07-02 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition containing pyridopyrimidine derivatives or pharmaceutically acceptable salts thereof |
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Open date: 20090715 |