CN108606963B - Compound contraceptive patch containing drospirenone and estrogen, preparation method and application - Google Patents
Compound contraceptive patch containing drospirenone and estrogen, preparation method and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
Abstract
The invention relates to the technical field of medicines, in particular to a compound contraceptive patch containing drospirenone and estrogen, and a preparation method and application thereof. The compound contraceptive plaster consists of a back lining layer, an anti-sticking layer and a medicine carrying layer, wherein the medicine carrying layer is coated on the back lining layer, the anti-sticking layer is covered on the medicine carrying layer, the anti-sticking layer is stripped when in use, and the contraceptive medicine in the medicine carrying layer comprises drospirenone serving as a contraceptive active component, estrogen serving as a synergistic contraceptive effect, a penetration enhancer and a medicine carrying material. The contraceptive patch is convenient to use, reduces the administration frequency, improves the compliance of a user, avoids gastrointestinal tract stimulation and liver first-pass effect caused by oral administration, can maintain stable release of the drug for a long time, avoids the peak valley phenomenon of blood concentration, and has obvious advantages compared with the compound drospirenone oral contraceptive on the market.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a compound contraceptive patch containing drospirenone and estrogen, and a preparation method and application thereof.
Background
The combined hormone contraceptive of progestogen and estrogen is a contraceptive mode which is most widely applied in the world at present. The first, second and third generation progestogens used clinically at present are mainly testosterone derivatives, and the compounds have no receptor selectivity and have some side effects besides progestogen activity.
Drospirenone is an aldosterone derivative, and the binding with progesterone receptor is more selective and specific, and the action is more similar to natural progesterone. Compared with the 1 st to 3 rd generation progestogens, the progestogens have no androgen, estrogen or glucocorticoid activity, so the safety is higher.
The compound oral contraceptive combining drospirenone and ethinylestradiol is a novel single-phase oral contraceptive, and the action mechanism of the compound oral contraceptive is that the contraceptive effect is achieved by inhibiting gonadotropin in a feedback manner, changing cervical mucus to enable sperms not to penetrate easily and interfering embryo implantation. However, the oral contraceptive needs to be taken continuously for 21 days in one physiological cycle, so that the compliance of a user is poor, and the situation of accidental pregnancy caused by missed taking is easy to occur. The oral contraceptive has liver first-pass effect, the bioavailability of the drospirenone and the ethinylestradiol is low, the blood concentration fluctuation is large, and some side effects are easy to cause.
The patch can improve the bioavailability of the medicine, maintain stable blood concentration and avoid peak-valley phenomenon by a transdermal administration mode. Meanwhile, the long-acting patch can reduce the administration frequency and improve the compliance of a user. Currently marketed contraceptive patches (trade name Evra) release 20 μ g of ethinyl estradiol and 150 μ g of methyl progesterone per day, 1 patch can be used for 7 days, and the application is stopped for 1 week after 3 weeks of continuous application per physiological cycle. However, methyl progesterone is a second-generation progestogen, and has a disadvantage of having many side effects. To date, no patent reports on a contraceptive patch containing drospirenone and estrogen have been found.
Chinese invention patent CN200580009528.4 discloses a skin pharmaceutical preparation containing drospirenone, including lotions, sprays and reservoir type transdermal patches. However, these preparations have a short drug release time and cannot achieve a controlled release effect over a long period of time.
Chinese invention patent No. cn200810018880.x discloses a transdermal absorption patch of gestodene and/or estrogen, which adopts two-layer to multi-layer patch technology to ensure constant release rate of the drug for a long time, but claimed gestodene is a third generation progestogen, and has greater side effects compared with fourth generation progestogen.
Chinese invention patent CN200910198769.8 discloses a compound contraceptive composition and a contraceptive transdermal patch containing the composition and a preparation method thereof, the medicament in the patent achieves the effect of long-acting release by distribution and diffusion in a skeleton polymer matrix and a pressure-sensitive adhesive matrix, but the progestogen which has the main contraceptive effect in the compound contraceptive composition is etoricoxib, which is an active metabolite of the third generation progestogen desogestrel.
Disclosure of Invention
The invention aims to provide a compound transdermal absorption contraceptive patch containing drospirenone and estrogen, secondly aims to provide a preparation method of the compound transdermal absorption contraceptive patch, and thirdly aims to provide application of the compound contraceptive patch in preparation of a contraceptive.
The compound transdermal absorption contraceptive patch containing the drospirenone and the estrogen disclosed by the invention can keep a stable drug transdermal rate within seven days, has a long-acting effect, can reduce the drug administration frequency of a user, and improves the compliance. Overcomes the defects of frequent use and poor compliance of the compound drospirenone oral contraceptive.
In order to achieve the purpose, the invention is implemented by the following technical scheme:
the invention provides a long-acting compound contraceptive patch, which consists of a back lining layer, an anti-sticking layer and a drug-loaded layer, wherein the contraceptive drugs in the drug-loaded layer comprise drospirenone which has the main contraceptive effect and estrogen which has the synergistic contraceptive effect.
In the compound contraceptive patch, the weight ratio of drospirenone to estrogen is 100:1-20: 1.
Preferably, the following components are adopted: the weight ratio of the drospirenone to the estrogen is 80:1-30: 1.
The reliability of the compound contraceptive patch is mainly provided by drospirenone, the daily dosage is at least the minimum value required for effectively inhibiting ovulation, and the estrogen is used for enhancing the ovulation inhibiting effect of drospirenone and ensuring the stability of the cycle.
In the compound contraceptive patch, the estrogen is selected from one of estradiol, ethinylestradiol, estrone, stilbestrol, chlorotriarylene, stilbestrol and pregnant marestrone. One of ethinyl estradiol, estradiol and estrone is preferable.
In the compound contraceptive patch, the drug-loaded layer consists of the following components in percentage by weight:
preferably, the following components are adopted:
the contraceptive patch is a solid skeleton type controlled release patch, the drug is dispersed in the drug-carrying material to serve as a drug storage, the drug-carrying layer is directly contacted with the skin of a human body when in use, and the drug is stably released from the drug storage into the human body through the controlled release effect of the drug-carrying material; the drug-carrying material is selected from one or two of pressure-sensitive adhesive and high molecular polymer.
The pressure-sensitive adhesive is one or more of thermoplastic elastomer pressure-sensitive adhesive, polysiloxane pressure-sensitive adhesive, polyisobutylene pressure-sensitive adhesive, polyacrylate pressure-sensitive adhesive or silicone pressure-sensitive adhesive. Preferred are polysiloxane pressure sensitive adhesives, polyisobutylene pressure sensitive adhesives or silicone pressure sensitive adhesives.
The high molecular material is selected from one or more of sodium alginate, sodium hydroxypropyl cellulose, polypropylene pyrrolidone, polyvinyl alcohol and sodium carboxymethyl cellulose.
One of the key problems of transdermal patches is the transdermal absorption of drugs, and thus the penetration-promoting technology becomes one of the key technologies for the formulation process. The invention adopts a method of adding a chemical penetration enhancer to improve the transdermal rate of the medicine in the patch. The penetration enhancer is selected from one or more of span80, menthol, lauric acid lactate, dimethyl sulfoxide, azone, oleic acid, glycerol, isopropyl myristate, propylene glycol, eucalyptol and N-methyl pyrrolidone.
The back lining layer is polyester film, polyethylene-vinyl acetate polymer film, polyethylene film or non-woven fabric, preferably polyethylene-vinyl acetate polymer film.
The anti-sticking layer is a polyethylene terephthalate film treated by a fluoride coating, and can effectively prevent the pressure-sensitive adhesive from being adhered.
The second aspect of the invention provides a preparation method of the compound contraceptive patch, which comprises the following steps:
A. mixing drospirenone, estrogen and organic solvent, stirring for dissolving, wherein the organic solvent is selected from ethyl acetate, acetone and ethanol;
B. adding a medicine carrying material and a penetration enhancer into the liquid medicine, and stirring and mixing at a stirring speed of 100-1000 rpm/min for 5-60 min;
C. and coating the liquid medicine containing the medicine carrying material and the penetration enhancer on the anti-sticking layer, drying for 0.2-1 hour at 50-100 ℃, and covering the back lining layer to obtain the product.
The contraceptive patch can permeate 0.3-2.3 mg of drospirenone through the skin every day, the daily permeation amount of ethinylestradiol through the skin is 10.8-17.7 mu g, and the administration area of each patch is 20-120cm2It is preferable.
The third aspect of the invention is to provide the application of the compound contraceptive patch in preparing a contraceptive.
The invention has the following beneficial effects:
the contraceptive patch can realize the effect of long-acting controlled release for 7 days, and the anti-sticking layer of the contraceptive patch is torn off when in use and is directly stuck on the skin of the lower abdomen, the hip, the upper arm or the upper back, and the anti-sticking layer needs to be replaced after one week. Beginning in the first week of the female's physiological cycle, 3 patches were used continuously, every 1 patch for 1 week. The use is stopped in the fourth week, and breakthrough bleeding can occur after the medicine is stopped, so that the effect of simulating the menstrual cycle of women is achieved. The contraceptive patch is convenient to use, reduces the administration frequency, improves the compliance of a user, avoids gastrointestinal tract stimulation and liver first-pass effect caused by oral administration, can maintain stable release of the medicament for a long time, and avoids peak-valley phenomenon of blood concentration. Compared with the compound drospirenone oral contraceptive on the market, has obvious advantages.
Drawings
Fig. 1 is a schematic structural diagram of the compound contraceptive patch of the present invention.
Fig. 2 is a graph showing the transdermal permeation profile of drospirenone over 7 days in examples 2-5 of the invention.
FIG. 3 is a graph showing the transdermal permeation profile of ethinylestradiol within 7 days according to examples 2 to 5 of the present invention.
Detailed Description
The following embodiments are implemented on the premise of the technical scheme of the present invention, and give detailed implementation modes and specific operation procedures, but the protection scope of the present invention is not limited to the following embodiments.
The reagents and starting materials used in the present invention are commercially available or can be prepared according to literature procedures. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.
Example 1
As shown in figure 1, the compound contraceptive patch 10 consists of a backing layer 11, an anti-adhesion layer 13 and a drug-loaded layer 12. The drug-loaded layer 12 is coated on the back lining layer 11, the anti-sticking layer 13 is covered on the drug-loaded layer 12, the anti-sticking layer 13 is peeled off when in use, and the contraceptive drug in the drug-loaded layer 12 comprises drospirenone which has the main contraceptive effect and estrogen which has the synergistic contraceptive effect. The specific formulation of the drug on the drug-loaded layer 12 is shown in examples 2-5.
Example 2
Prescription: 0.3g of drospirenone, 6mg of ethinylestradiol, 0.15g of azone and 6g of polyacrylate pressure-sensitive adhesive.
The preparation method comprises the following steps: adding drospirenone and ethinylestradiol into 4g of ethyl acetate, and stirring to dissolve to obtain a liquid medicine for later use. Adding polyacrylate pressure-sensitive adhesive and azone into the medicinal liquid, stirring at 800rpm/min for 30min, standing, and degassing to obtain medicinal liquid. Coating the medicinal glue solution on the anti-sticking layer, drying at 50 deg.C for 30min, and covering with backing layer to obtain the final product. The release layer was a release film model 9744 from 3M company, usa, and the backing layer was a backing film model 9680 from 3M company, usa. Preparation ofTo a composition containing drospirenone 1.14mg/cm20.023mg/cm of ethinyl estradiol2The patch of (1).
Determination of in vitro transdermal permeation rate: the patch is adhered to the cutin layer of the skin of a nude mouse by adopting a Franz vertical diffusion cell and is clamped between a receiving cell and a sample cell, and the dermis layer of the skin of the nude mouse faces the receiving cell. Constant temperature water bath at 32 deg.C, transdermal area of 2.5 cm2The volume of the receiving tank is 7mL, and the stirring speed is 100 r.min-1. The physiological saline containing 5% ethanol is used as receiving medium, and 0.01% penicillin sodium is added into the receiving medium to prevent skin putrefaction. The transdermal permeation rate of drospirenone is 1.08 μ g cm-2·h-1The transdermal penetration rate of ethinylestradiol is 4.50ng cm-2·h-1. The transdermal permeation curve of drospirenone is shown in figure 1, and that of ethinylestradiol is shown in figure 2.
Example 3
Prescription: 1g of drospirenone, 10mg of ethinylestradiol, 0.1g of menthol, isopropyl myristate and 10g of polyisobutylene pressure-sensitive adhesive.
The preparation method comprises the following steps: adding drospirenone and ethinylestradiol into 8g of acetone, and stirring to dissolve to obtain a liquid medicine for later use. Adding polyisobutylene pressure sensitive adhesive, menthol and isopropyl myristate into the medicinal liquid, stirring at 600rpm/min for 40min, standing, and degassing to obtain medicinal liquid. Coating the medicinal glue solution on the anti-sticking layer, drying at 70 deg.C for 30min, and covering with backing layer to obtain the final product. The release layer was a type 9748 release film from 3M company, USA, and the backing layer was a type 9718 backing film from 3M company, USA. Prepared to contain drospirenone 0.73mg/cm2Ethinyl estradiol 0.042mg/cm2The patch of (1).
Determination of in vitro transdermal permeation rate: the patch is adhered to the cutin layer of the skin of a nude mouse by adopting a Franz vertical diffusion cell and is clamped between a receiving cell and a sample cell, and the dermis layer of the skin of the nude mouse faces the receiving cell. Constant temperature water bath at 32 deg.C, transdermal area of 2.5 cm2The volume of the receiving tank is 7mL, and the stirring speed is 100 r.min-1. The physiological saline containing 5% ethanol is used as receiving medium, and 0.01% penicillin sodium is added into the receiving medium to prevent skin putrefaction. The transdermal permeation rate of drospirenone is 0.78 μ g cm-2·h-1The transdermal penetration rate of ethinylestradiol is 5.70ng cm-2·h-1. The transdermal permeation curve of drospirenone is shown in figure 1, and that of ethinylestradiol is shown in figure 2.
Example 4
Prescription: 0.4g of drospirenone, 20mg of ethinylestradiol, 0.1g of oleic acid and 8g of polysiloxane pressure-sensitive adhesive.
The preparation method comprises the following steps: adding drospirenone and ethinylestradiol into 4g of acetone, and stirring to dissolve to obtain medicinal liquid for later use. Adding silicone pressure sensitive adhesive and oleic acid into the medicinal liquid, stirring at 500rpm/min for 20min, standing, and degassing to obtain medicinal liquid. Coating the medicinal glue solution on the anti-sticking layer, drying at 60 deg.C for 20min, and covering with backing layer to obtain the final product. The release layer was a model 1020 release film from 3M company, USA, and the backing layer was a model 9736 backing film from 3M company, USA. Prepared into the medicine containing drospirenone 0.82mg/cm20.032mg/cm ethinylestradiol2The patch of (1).
Determination of in vitro transdermal permeation rate: the patch is adhered to the cutin layer of the skin of a nude mouse by adopting a Franz vertical diffusion cell and is clamped between a receiving cell and a sample cell, and the dermis layer of the skin of the nude mouse faces the receiving cell. Constant temperature water bath at 32 deg.C, transdermal area of 2.5 cm2The volume of the receiving tank is 7mL, and the stirring speed is 100 r.min-1. The physiological saline containing 5% ethanol is used as receiving medium, and 0.01% penicillin sodium is added into the receiving medium to prevent skin putrefaction. The transdermal permeation rate of drospirenone is 0.69 μ g cm-2·h-1The transdermal penetration rate of ethinylestradiol is 13ng cm-2·h-1. The transdermal permeation curve of drospirenone is shown in figure 1, and that of ethinylestradiol is shown in figure 2.
Example 5
Prescription: 2g of drospirenone, 30mg of ethinylestradiol, 0.15g of eucalyptol, 6g of silicone pressure-sensitive adhesive and 6g of sodium alginate.
The preparation method comprises the following steps: adding drospirenone and ethinylestradiol into 8g of ethanol, and stirring to dissolve to obtain medicinal liquid for later use. Adding silicone pressure sensitive adhesive, sodium alginate and eucalyptol into the medicinal liquid, stirring at 300rpm/min for 50min, standing, and degassing to obtain medicinal liquid. Coating the medicinal glue solution on the anti-sticking layer, and drying at 70 deg.CDrying for 10min, and covering with backing layer to obtain the final product. The anti-sticking layer is made of non-woven fabric, and the backing layer is made of a 9722 type backing film of American 3M company. Prepared into the medicine containing drospirenone 0.65mg/cm2Ethinyl estradiol 0.018mg/cm2The patch of (1).
Determination of in vitro transdermal permeation rate: the patch is adhered to the cutin layer of the skin of a nude mouse by adopting a Franz vertical diffusion cell and is clamped between a receiving cell and a sample cell, and the dermis layer of the skin of the nude mouse faces the receiving cell. Constant temperature water bath at 32 deg.C, transdermal area of 2.5 cm2The volume of the receiving tank is 7mL, and the stirring speed is 100 r.min-1. The physiological saline containing 5% ethanol is used as receiving medium, and 0.01% penicillin sodium is added into the receiving medium to prevent skin putrefaction. The transdermal permeation rate of drospirenone is 0.39 μ g cm-2·h-1The transdermal penetration rate of ethinylestradiol is 2.50ng cm-2·h-1. The transdermal permeation curve of drospirenone is shown in figure 1, and that of ethinylestradiol is shown in figure 2.
Example 6: formulation optimization
The permeation promoting effect of 4 common chemical permeation promoters on the drugs is examined. Acrylate pressure-sensitive adhesive is used as a skeleton controlled-release material, the added dosage is 20% (drospirenone: ethinylestradiol: 50: 1), and Azone (Azone) with the mass fraction of 5%, Oleic acid (Oleic acid) with the mass fraction of 5%, Isopropyl myristate (isoproyl myristate) with the mass fraction of 5% and Span80 (Span80) with the mass fraction of 5% are respectively used as penetration promoters. The preparation method and the in vitro transdermal permeation rate measuring method are the same as those of example 5.
The influence of different penetration enhancers on the transdermal permeation behavior of drospirenone is shown in table 1, which shows that the transdermal permeation behavior of drospirenone in the patch for 72 hours better follows the zero order kinetic equation after adding different penetration enhancers. The amount of permeation per unit area is proportional to time. The penetration promoting effect of the added 4 penetration promoters on the drospirenone is not obvious, wherein 5% by mass of isopropyl myristate has a certain inhibiting effect on the transdermal penetration of the drospirenone.
The influence of different permeation promoters on the percutaneous permeation behavior of ethinylestradiol is shown in table 2, and table 2 shows that 4 permeation promoters have an arrangement sequence from large to small for ethinylestradiol permeation promotion, wherein the arrangement sequence is that azone with a mass fraction of 5% is larger than 5% of isopropyl myristate with a mass fraction of 5% is larger than 5% of oleic acid with a mass fraction of 5% of span 80. The infiltration-promoting multiple of 5 percent azone by mass is 2.1, and the infiltration-promoting effect is obvious (P is less than 0.05).
TABLE 1 fitting results of drospirenone transdermal penetration behavior in compound contraceptive patch
TABLE 2 fitting results of ethinylestradiol transdermal penetration behavior in compound contraceptive patch
While the preferred embodiments of the present invention have been described in detail, it will be understood by those skilled in the art that the invention is not limited thereto, and that various changes and modifications may be made without departing from the spirit of the invention, and the scope of the appended claims is to be accorded the full scope of the invention.
Claims (10)
1. A compound contraceptive patch comprises a back lining layer, an anti-sticking layer and a drug-loaded layer, wherein the drug-loaded layer is coated on the back lining layer, the anti-sticking layer covers on the drug-loaded layer and is peeled off during use, the contraceptive drug in the drug-loaded layer comprises drospirenone which is used as a contraceptive active component, ethinylestradiol which has a synergistic contraceptive effect, a penetration enhancer and a drug-loaded material,
wherein the concentration of drospirenone in the contraceptive patch is 0.65-1.14 mg/cm2The concentration of ethinylestradiol is 0.018-0.042 mg/cm2The patch of (1) above, wherein,
the penetration enhancer is azone.
2. The compound contraceptive patch according to claim 1, wherein the drug in the drug-loaded layer is dispersed in the drug-loaded material, and the contraceptive effect is achieved through the controlled release effect of the drug-loaded material.
3. The compound contraceptive patch according to claim 1, wherein the weight ratio of drospirenone to ethinylestradiol is 50: 1.
4. the compound contraceptive patch as claimed in claim 1, wherein the drug-loaded layer comprises the following components by weight percent:
5. the compound contraceptive patch as claimed in claim 1, wherein the drug-loaded layer comprises the following components by weight percent:
6. the compound contraceptive patch according to claim 4 or 5, wherein the drug-loaded material is selected from one or two of pressure-sensitive adhesive and high molecular polymer;
the pressure-sensitive adhesive is selected from polyacrylate pressure-sensitive adhesives;
the high molecular polymer is one or more of sodium alginate, sodium hydroxypropyl cellulose, polypropylene pyrrolidone, polyvinyl alcohol and sodium carboxymethyl cellulose.
7. The preparation method of the compound contraceptive patch as claimed in claim 1, which is characterized by comprising the following steps:
A. mixing drospirenone, ethinylestradiol and an organic solvent, and stirring for dissolving for later use;
B. adding a medicine carrying material and a penetration enhancer into the liquid medicine, and stirring and mixing at a stirring speed of 100-1000 rpm/min for 5-60 min;
C. and coating the liquid medicine containing the medicine carrying material and the penetration enhancer on the anti-sticking layer, drying and cooling, and covering the back lining layer to obtain the product.
8. The preparation method of the compound contraceptive patch as claimed in claim 7, wherein the drying temperature in step C is 50-100 ℃ and the drying time is 0.2-1 hour.
9. The method for preparing a compound contraceptive patch as claimed in claim 7, wherein the organic solvent in step A is selected from ethyl acetate, acetone or ethanol.
10. Use of a compound contraceptive patch according to claim 4 or 5 in the manufacture of a contraceptive device.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1407895A (en) * | 1999-08-31 | 2003-04-02 | 先灵公司 | Pharmaceutical combination of ethinylestradiol and drospirenone for use as contraceptive |
| CN1933843A (en) * | 2004-04-01 | 2007-03-21 | 舍林股份公司 | Pharmaceutical preparation containing drospirenone for application to the skin |
| CN101700246A (en) * | 2009-11-13 | 2010-05-05 | 上海现代药物制剂工程研究中心有限公司 | Compound contraceptive composition, contraceptive transdermal patch containing composition and preparation method |
| CN102119021A (en) * | 2008-08-08 | 2011-07-06 | 拜耳先灵医药股份有限公司 | Progestin-containing drug delivery system |
-
2017
- 2017-12-27 CN CN201711448929.0A patent/CN108606963B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1407895A (en) * | 1999-08-31 | 2003-04-02 | 先灵公司 | Pharmaceutical combination of ethinylestradiol and drospirenone for use as contraceptive |
| CN1933843A (en) * | 2004-04-01 | 2007-03-21 | 舍林股份公司 | Pharmaceutical preparation containing drospirenone for application to the skin |
| CN102119021A (en) * | 2008-08-08 | 2011-07-06 | 拜耳先灵医药股份有限公司 | Progestin-containing drug delivery system |
| CN101700246A (en) * | 2009-11-13 | 2010-05-05 | 上海现代药物制剂工程研究中心有限公司 | Compound contraceptive composition, contraceptive transdermal patch containing composition and preparation method |
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