CN102274235B - New contraceptive medicinal composition and preparation method thereof - Google Patents
New contraceptive medicinal composition and preparation method thereof Download PDFInfo
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- CN102274235B CN102274235B CN 201110174656 CN201110174656A CN102274235B CN 102274235 B CN102274235 B CN 102274235B CN 201110174656 CN201110174656 CN 201110174656 CN 201110174656 A CN201110174656 A CN 201110174656A CN 102274235 B CN102274235 B CN 102274235B
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- drospirenone
- ethinylestradiol
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Abstract
The invention relates to a new contraceptive medicinal composition and a preparation method thereof. The composition is prepared by dissolving medicinal active ingredients in a solvent and mixing the solution with pharmaceutically acceptable excipient. The optimal medicinal active ingredients of the medicinal composition are drospirenone and ethinyloestradiol which are in a weight ratio of 3:0.03; and the composition is prepared by dissolving the drospirenone and ethinyloestradiol in solvent which is a mixture of acetone and ethanol in a volume to volume ratio of (1-3):(6-8) and mixing the solution with the pharmaceutically acceptable excipient.
Description
Technical field:
The present invention relates to a kind of with drospirenone and ethinylestradiol as the new compositions of contraceptive, improve dissolution and preparation method.
Background technology:
Bring into use progestogen and estrogen to unite the oral contraceptive of composition from the sixties in 20th century, and the contraception the effective elements of the medicine is provided by the progestogen composition, estrogenic component mainly strengthens the ovulation inhibition effect of progestogen and guarantees the stable cycle.Since oral contraceptive came out, the countries in the world research worker researchs and develops the higher progestin preparation of selectivity always so that progestin dosage reduces, and keeps simultaneously its high efficiency, good cycle regulating, and rate of side effects is low.Estrogen dosage is lowered gradually, from 150 μ g to being lower than 50 μ g, even to 15 μ g.Now mainly prove after for many years domestic and international clinical trial take ethinylestradiol as main warp, with older generation's progesterone compatibility, estrogenic component is lower than the purpose that 30 μ g then can not reach the safety contraception, with high selectivity progestogen desogestrel compatibility, makes the minimizing estrogen dosage become possibility; The up-to-date oral contraceptive of 3mg drospirenone and 0.03mg ethinylestradiol composition has been ratified in Europe in calendar year 2001 for this reason.
Drospirenone (Drospirenone) is a kind of derivant of 17a-spironolactone, synthetic progestogen of new generation, with pregnant intoxicated similar, with progesterone receptor, mineralcorticoid receptor affinity is highly arranged, very low with androgen receptor and glucocorticoid receptor (GR) affinity, be not combined with estrogen receptor.The steroid contraceptive that makes it become a kind of efficient, low toxicity, have no side effect, effect with anti mineralocorticoid and androgen antagonist, oral contraceptive has desirable influence to bone metabolism, so this medicine is particularly useful for having the bone amount to reduce and the dangerous women that also need to take contraceptive of osteoporosis.
Summary of the invention:
The invention provides a kind of pharmaceutical composition, said composition is comprised of active constituents of medicine and the acceptable excipient of pharmacy, it is characterized in that, said composition is with after the active constituents of medicine dissolving, with the acceptable mixed with excipients preparation of pharmacy with solvent.
Pharmaceutical composition of the present invention, preferred active constituents of medicine is drospirenone and ethinylestradiol, both part by weight are: 3: 0.03, said composition is to use acetone: ethanol=1-3: the mixture of 6-8 (v/v) is solvent, after the dissolving of drospirenone and ethinylestradiol, with the acceptable mixed with excipients preparation of pharmacy.
The preferred acetone of solvent: ethanol=3: 7 (v/v).
Because drospirenone is a kind of water medicine that is slightly soluble in, its characteristic is can be rearranged under the acid condition not have activated isomer, alkali condition is next can hydrolysis. and ethinylestradiol is a kind of medicine of water fast, drug regimen of the present invention adopts human body acceptable acetone or/and alcohol mixed solvent dissolving drospirenone and ethinylestradiol and subsequently on suitable pharmaceutical excipient and additives can effectively improve dissolution; Adopt on this basis the rapid release film coating or be filled in the capsule shells; Reduce the degraded of drug regimen in gastroenteric environment, its drug regimen is absorbed rapidly in vivo, thereby guarantee that this medicine has good bioavailability.
Excipient preferred starch of the present invention, pregelatinized Starch, lactose monohydrate, lactose, mannitol, sorbitol, saccharide (monosaccharide and polysaccharide), microcrystalline Cellulose and its ester and salt and relative mixture thereof, hydroxypropyl methylcellulose, croscarmellose is received, carboxymethyl cellulose and its calcium and sodium, polyvidone, calcium phosphate, stearic acid, magnesium stearate, silicon dioxide, Pulvis Talci, Polyethylene Glycol, titanium dioxide, yellow iron oxide, red iron oxide or in them one or more mixture and have this area known material of knowledge personnel or/and similar substance.
The present invention also comprises the preparation method of the present composition, comprising drospirenone and ethinylestradiol are dissolved in acetone: in the mixture of ethanol=3: 7 (v/v), be mixed together granulation with other excipient again, further be prepared into tablet or capsule.
Acetone of the present invention: its consumption of mixture of ethanol=3: 7 is 20ml-100ml for preparing 1000 Tablet and Capsula consumptions.
Compositions of the present invention can be tablet, also can be capsule, and tablet is preferably used film coating.
Compositions of the present invention, wherein particularly preferred prescription is as follows:
The rapid release coating materials:
Preparation method:
Get proper amount of acetone/ethanol (3: 7) solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves (HHY solution) fully.
Each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use.
Starch, lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose are received, polyvidone is crossed respectively the 60-100 order, insert abundant mix homogeneously in the mixer.
Mixed powder and HHY solution are brought together in mixer, the 20-40 order is granulated; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate.Add the magnesium stearate mix homogeneously, check, tabletting.
Coating solution is plain coating tablets.
Another particularly preferred prescription is as follows:
Get proper amount of acetone/ethanol (3: 7) solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves (HHY solution) fully.
Each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use.
Starch, lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose are received, polyvidone is crossed respectively 80 orders, insert abundant mix homogeneously in the mixer.
Mixed powder and HHY solution are brought together in mixer, the 20-40 order is granulated; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate.Add the magnesium stearate mix homogeneously, check, No. 5 capsule-fillings.
Compositions of the present invention is compared with the similar drug that has gone on the market has significant superiority: such as dissolution relatively: relevant data is seen Figure of description.
The present invention adopts solvent acetone: ethanol=3: 7 (v/v) dissolves principal agent and the method for granulating obtains through screening, and screening process is as follows:
Design following ratio solvent, measure respectively an amount of solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves (HHY solution) fully.
Each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use.
Starch, lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose are received, polyvidone is crossed respectively 80 orders, insert abundant mix homogeneously in the mixer.
Mixed powder and HHY solution are brought together in mixer, the 20-40 order is granulated; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate.Add the magnesium stearate mix homogeneously, check, tabletting, coating.And mensuration dissolution.
| Sequence number | Acetone: ethanol | Drospirenone dissolution (%) | Ethinylestradiol dissolution (%) |
| 1 | 5∶5 | 92 | 90 |
| 2 | 4∶6 | 90 | 91 |
| 3 | 3∶7 | 92 | 91 |
| 4 | 2∶8 | 91 | 92 |
| 5 | 1∶9 | 85 | 83 |
Comprehensive above-mentioned result of the test is with effectiveness, the safety of medicine; But the endurance of human body and environment, preferred solvent acetone: ethanol=3: 7 (v/v).
The present invention also has following advantage:
1, the present invention uses and volatilely surveys residual " 3 class " solvent, but the human body receiving amount is large, and higher safety is arranged.
2, the selected adjuvant wide material sources of the present invention, production cost is low.
3, preparing product of the present invention adopts film coating and softgel shell, has reduced isomerization and the hydrolysis of medicine in gastrointestinal, and the bioavailability that effectively improves medicine is high.
Description of drawings:
Fig. 1 drospirenone stripping curve figure
Fig. 2 ethinylestradiol stripping curve figure
The specific embodiment:
Further specify by the following examples the present invention, but not as limitation of the present invention.
The element sheet:
The rapid release coating materials:
Preparation method:
1, gets proper amount of acetone/ethanol (3: 7) solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves (HHY solution) fully.
2, each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use.
3, starch, lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose are received, polyvidone crosses respectively the 60-100 order, insert in the mixer fully mix homogeneously.
4, mixed powder and HHY solution are brought together in mixer, the 20-40 order granulates; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate.Add the magnesium stearate mix homogeneously, check, tabletting.
5, coating solution is plain coating tablets.
Embodiment 2,
Adopt material and preparation method among the embodiment 1 to prepare a batch sample, wherein solvent adopts the acetone/ethanol mixture, and wherein ratio is also can obtain embodiment 1 described result at 2: 8.
1, gets proper amount of acetone/ethanol (3: 7) solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves (HHY solution) fully.
2, each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use.
3, starch, lactose monohydrate, hydroxypropyl methylcellulose, croscarmellose are received, polyvidone crosses respectively the 60-100 order, insert in the mixer fully mix homogeneously.
4, mixed powder and HHY solution are brought together in mixer, the 20-40 order granulates; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate.Add the magnesium stearate mix homogeneously, check, No. 5 capsule-fillings.
Embodiment 4,
Adopt material and preparation method among the embodiment 3 to prepare a batch sample, wherein solvent adopts the acetone/ethanol mixture, and wherein ratio is also can obtain embodiment 3 described results at 2: 8.
Each implements the check item result of sample:
Claims (1)
1. a pharmaceutical composition is characterized in that, said composition is comprised of active constituents of medicine and the acceptable excipient of pharmacy, it is characterized in that, it is as follows to fill a prescription
The element sheet:
The rapid release coating materials:
Preparation method:
Get proper amount of acetone/ethanol=3:7 solvent and place the rustless steel agitating device, then under constant stirring, add ethinylestradiol and the drospirenone of recipe quantity, and be stirred to ethinylestradiol and drospirenone dissolves fully, get HHY solution,
Each composition of coating materials is mixed with an amount of 95% ethanol, for subsequent use,
Starch, pre-paying starch, lactose monohydrate, PVP K30, croscarmellose are received and are crossed respectively the 60-100 order, insert abundant mix homogeneously in the mixer,
Mixed powder and HHY solution are brought together in mixer, the 20-40 order is granulated; 20 ℃ of-90 ℃ of dryings, 20-40 order granulate adds the magnesium stearate mix homogeneously, check, tabletting,
Coating solution is plain coating tablets.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110174656 CN102274235B (en) | 2011-06-27 | 2011-06-27 | New contraceptive medicinal composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110174656 CN102274235B (en) | 2011-06-27 | 2011-06-27 | New contraceptive medicinal composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102274235A CN102274235A (en) | 2011-12-14 |
| CN102274235B true CN102274235B (en) | 2013-03-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110174656 Expired - Fee Related CN102274235B (en) | 2011-06-27 | 2011-06-27 | New contraceptive medicinal composition and preparation method thereof |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101022811A (en) * | 2004-08-09 | 2007-08-22 | 利肯萨实验室股份有限公司 | Pharmaceutical composition comprising drospirenone and ethynylestradiol |
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2011
- 2011-06-27 CN CN 201110174656 patent/CN102274235B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101022811A (en) * | 2004-08-09 | 2007-08-22 | 利肯萨实验室股份有限公司 | Pharmaceutical composition comprising drospirenone and ethynylestradiol |
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| CN102274235A (en) | 2011-12-14 |
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