CN1546043A - Percutaneous formula of natural gestagen and its preparation - Google Patents
Percutaneous formula of natural gestagen and its preparation Download PDFInfo
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- CN1546043A CN1546043A CNA2003101169042A CN200310116904A CN1546043A CN 1546043 A CN1546043 A CN 1546043A CN A2003101169042 A CNA2003101169042 A CN A2003101169042A CN 200310116904 A CN200310116904 A CN 200310116904A CN 1546043 A CN1546043 A CN 1546043A
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Abstract
The invention discloses a natural progestational hormone perchloromethane preparation and process for making it, wherein the natural progestational hormone perchloromethane preparation comprises 5-40 wt% of natural progestational hormone and 40-60 wt% of transparent promoting agent, which can exist in the forms of plaster, perchloromethane plaster, liposome and microcapsule.
Description
Technical field
The present invention relates to natural progestogen percutaneous preparation and preparation method thereof.
Background technology
Climacteric is the transition stage that ovarian function fails gradually and disappears to the end.The women generally entered into the climacteric period between 45～55 years old.Climacteric syndrome is meant the menoxenia that the women occurs that enters into the climacteric period, paroxysmal hectic fever, sweating, cardiopalmus is nervous, chest distress, and it is dizzy to have a headache, insomnia and dreamful sleep, or depressed worried, and spirit is uneasy, emotional, hypomnesis, inappetence or abdominal distention diarrhoea, constipation, edema, unstable blood pressure, fluctuated, paraesthesia or the like.These a series of symptoms are referred to as climacteric syndrome.The reason that causes all diseases of climacteric mainly is because hypo-ovaria, makes organism endocrine functional disorder and autonomic nervous system dysfunction, adds due to the influence of psychological factor and various social factors.
(hormone replacement therapy HRT) can alleviate menopausal symptom to hormone replacement therapy effectively.Use estrogen from 1932 and prevent and treat climacteric syndrome, recognized a series of degenerations changes such as climacteric syndrome that preventative estrin treatment can delay or stop ovarian function failure and cause, urogenital tract atrophy, osteoporosis, arteriosclerosis in 1963.
1, HRT is to the favourable part of menopausal women:
(1) menoxenia to the excessive phase of menopause has regulating action
(2) the unstable symptom of alleviating vascular motor function
50% above postmenopausal women has hectic fever, night sweat and insomnia, also possibility anxiety, depression and urogenital tract atrophy, diseases such as very easy elimination hectic fever of Hormone Replacement Therapy and urogenital tract atrophy.Report is arranged, and the effective percentage of medication during 8 weeks is 90%～95%.
(3) reduce losing rapidly of bone amount after the menopause
Albright etc. (1941) recognize that at first estrogen deficiency is the major reason of menopausal osteoporosis disease.After this many researchs confirm that all estrogen can prevent osteoporosis.Controversies in hormone replacement in the elderly reduces patient's osteoporotic fracture, prevents further bone loss and has stablized bone density.Bone loss after with menopause several leading year the most very, approximately annual 1%～3%.This sclerotin quickens to run off and lasted till 75 years old always.Adopt the above person of HRT6, hipbone or fracture of the carpal bone danger can reduce 50%, and the vertebral malformation incidence rate reduces 90%, and HRT stops, and bone loss quickens again.Research thinks that the best estrogen dosage of keeping the bone amount is to connect estrogen 0.625mg/ days, estradiol 2mg/ days.
(4) reduce ischemic cardiovascular danger and case fatality rate
Epidemiological studies shows that the danger that the postmenopausal women adopts natural estrogen replacement therapy person that ischemic cardiovascular takes place reduces by 35%～45%, and myocardial infarction is dangerous to reduce about 50%.In the mechanism of estrogen decrease coronary risk factor, improve blood fat and account for 25%～50%, other effect comprises and improves cardiac function, coronary artery dilator and cerebral arteries, reduction vascular resistance, increases cardiac output, reduces on the arterial wall atherosis speckle etc.Suffered from the ischemic heart patient, estrogen can improve the ischemic electrocardiogram and change, and reduces cardiac preload etc., thereby estrogen may become the ingredient of postmenopausal women's therapeutic scheme of suffering from coronary heart disease.
(5) reduce the alzheimer disease incidence rate
Alzheimer disease (Alzheirmer ' s disease.AD) is modal a kind of dementia, and the women suffers from more.Have been found that and contain estrogen receptor and estrogen in the hippocampus that has memory function in the brain that women more of the same age is low for level for serum OES among the AD patient (main estrogen in postmenopausal women's body).After women's both ovaries excision before the menopause, 65 years old elderly woman, after ragazza factor palace muscular tumor application GnRH-a causes that body inner estrogen level reduction person uses estrogen, the increase of keeping the score of its language memory, then obviously reduce without the person, point out exogenous estrogen to help to keep and cerebral function improvement.After the U.S. has the people to 472 menopause or perimenopausal women with examining 16 years, find to use the estrogen person, AD is dangerous to reduce by 54%, user AD morbidity never increases by 2.2 times.When the women who has suffered from AD uses estrogen, its orientation force and computing power improve, the psychometry increase of keeping the score, therefore, estrogen may become one of active drug of treatment and prevention AD, its mechanism may be the acetylcholine metabolism that improves depressive state, improves cerebral blood flow, stimulates the central nervous system, increases the glial cell quantity of developmental pattern and supports function of nervous system.
2, with the HRT diseases associated
(1) carcinoma of endometrium
At any time singly using estrogen, the relative risk of carcinoma of endometrium is 3.0 or more, along with administration time prolongs, danger increases gradually, use more than the 10-15, the relative risk of carcinoma of endometrium reaches 10 approximately, but this endometrial carcinomas mostly is in early days, grade malignancy is low, prognosis is better.Add with behind the progestogen, can significantly reduce the generation of carcinoma of endometrium, endometrial incidence rate is identical or lower with patient without HRT.Progestogen prevent that the effect of carcinoma of endometrium from can and reduce cell proliferation and realize by the E2 receptor that reduces nuclear, anti-DNA (deoxyribonucleic acid) synthetic.Endometrial proliferation takes place in the estrin treatment patient 20%～30% who does not have antagonism, reduces to reduce in 4%, 10 day with 7 days its incidence rates of progestogen and reduces to 0 in 2%, 12 day.
(2) breast carcinoma
The relation of HRT and breast carcinoma is still disputable.The most studies result shows at present, uses estrogen can increase the danger that suffers from breast cancer after 10～15 years.Colditz etc. combine 31 epidemiological studies and show that the women breast cancer RR that is using HRT is 1.02-1.40, the course of treatment 〉=5-10 person RR is 1.46.Age 60-64 year person RR is 1.71.Prompting is being used HRT person and should monitored mammary gland, especially older, course of treatment the elder.There is not evidence to show to have the family history of breast cancer that the person accepts the generation that HRT can increase breast carcinoma, but general Ying Shenyong.Accepting Prognosis in Breast Cancer that HRT takes place therebetween, not accept HRT person good, and the time-to-live is long, is risky but the person that do not suffer from breast cancer accepts HRT.
(3) thrombotic disease
Previously think oral contraceptive can reduce Antithrombin III and fibrinoclase unit and easy hyperamization bolt, be mainly seen in when taking some synthetic estrogen.Advocate the HRT of minimum effective dose now, still not having the HRT of studies confirm that so far can increase thrombotic disease.Also no evidence shows that natural estrogen and thromboembolism form have cause effect relation.
(4) diabetes
Heavy dose of norethindrone class progesterone has insulin resistance, and carbohydrate tolerance is reduced; But estrogen replacement therapy blood sugar lowering and insulin level, the sensitivity of increase insulin.
(5) hypertension
Angiotensinogen increases nervous plain II of comes and aldosterone increase during oral estrogen.Percutaneous E2 does not have this effect.Most of research reports continue Hormone Replacement Therapy not to be had significant change or reduction trend is arranged blood pressure.
(6) cholelithiasis
There are some researches show that estrogen may increase the chance that cholelithiasis forms, because of reducing chenodeoxy cholic acid in the bile.
The medicine of HRT is divided into oral and non-intestinal by application method and uses two kinds.Oral is the most frequently used clinically application method.Drug oral enters blood circulation after liver sausage circulates, remakes to be used for target organ, so estrogen concentrations is easy to fluctuation in the blood, and influential to the metabolism of liver.Non-intestinal uses: mainly comprise through skin (skin pastes, skin buries and smear cream or glue) and transvaginal and use (frost, sheet, bolt, falope ring).Its advantage is available natural female, progestogen, does not need the liver sausage circulation, and medicine can directly enter the body circulation, and the oral natural progestogen at liver through the destroyed sprout of first pass effect to the greatest extent.In view of the extensive use of progestogen in the department of obstetrics and gynecology field, and the low characteristics of natural progestogen side effect, develop non-enteral product and press in fact.
Summary of the invention
The purpose of this invention is to provide a kind of natural progestogen percutaneous preparation and preparation method thereof.
For achieving the above object, the present invention takes following scheme:
I. natural progestogen percutaneous preparation of the present invention comprises following components by weight proportion:
Natural progestogen 5～40wt%
Penetration enhancer 40～60wt%
Natural progestogen can be chosen from following material:
Conjugated estrogen hormone: be that the multiple estrogen that extracts in the mare urine by pregnancy mixes, contain compositions such as water solublity estrone sodium sulfate, equilin sodium sulfate, (.+-.)-Equilenin. sodium sulfate.The pharmacological action of conjugated estrogen hormone is similar to the estrogenic pharmacological action of interior life.
Estradiol valerate: be long-acting derivatives of estradiol, can alleviate the menopausal symptom that causes because of estrogen deficiency; To skin and the urogenital mucous membrane degeneration effect of having clear improvement; Postmenopausal osteoporosis there is preventive effect.Be used for hypoovarianism, amenorrhea, climacteric syndrome, move back milk and carcinoma of prostate etc.
Estradiol benzoate: be the benzoate of estradiol.Action time is longer, can keep 2～3, is one of at present the most frequently used estrogen, is oil solvent.
Estradiol cypionate: be the cipionate of estradiol.Also be the Delestrogen preparation, act on byer force and lasting, hold time more than 3～4 weeks than estradiol valerate.
Progesterone: a kind of natural progestogen, periodically secrete a large amount of Progesterone of gravid woman's placenta secretion (reach as high as non-pregnancy period 1000 times) by women of child-bearing age's corpus luteum.The main effect of progesterone is to suppress uterine contraction, and helps endometrium to be transformed to the secretory phase by proliferative phase.Progesterone has been widely used in for many years clinical, is used to prevent miscarriage, and can treats diseases such as amenorrhea, dysfunctional uterine hemorrhage, endometriosis, carcinoma of endometrium, also share with estrogen, forms contraceptive and hormone replacement therapy.
The mechanism of action of penetration enhancer mainly is to change skin texture by reversibility to penetrate into skin and reduce medicine through the suffered resistance of skin, reaches the purpose that promotes absorption of medicine whole body or topical therapeutic.
Natural penetration enhancer: comprise terpenoid, quintessence oil, lactone etc., as book lotus brain, Borneolum Syntheticum, Oleum Eucalypti, Rhizoma Chuanxiong, Elettaria cardamomum (L.) Maton, Aloe extract etc.
II. natural progestogen percutaneous preparation of the present invention can be taked following pattern:
(1) mastic: characteristics are the carriers that not only can be used as active component, make it to be absorbed by skin.Can also replenish suitable moisture of skin and oil content, have good use feeling, have the pharmaceutically-active purpose that reaches conditioning and skin nutrition simultaneously.
(2) the percutaneous skin pastes: the estrogen and progestogen during skin pastes, be dissolved in the storage layer of bonding alcohol, and there is the protection thing to adhere to thereafter, be affixed on the skin, make hormone form semipermeable membrane.
(3) liposome: liposome is with its excellent biological compatibility and promote the characteristic of drug transdermal absorption more and more to be subject to people's attention.The class lipid bilayer structure of liposome can be effectively combines with hydrophilic, lipophilic and macromolecular drug, with drug encapsulation in wherein, similar " organic solvent " increases the dissolubility of medicine, increase local drug concentration, can promote medicine to see through skin effectively, can play storage storehouse and speed limit effect again, thereby the control rapid release of realizing medicine be put, improve bioavailability of medicament, reduce side effect.
(4) microcapsule: exactly active component is wrapped in the microcapsule with certain surface characteristic, in use, active component is progressively discharged from microcapsule by the speed of wishing in advance according to the principle of slow releasing function.The realization of this technology need be satisfied two conditions: the one, and active component must be able to be wrapped in the microcapsule, and the 2nd, have suitable character as the microcapsule of transportation media and under the condition of hope, can discharge with the active component of guaranteeing to wrap in wherein.
The preparation method of natural progestogen percutaneous preparation III. of the present invention:
(1) natural progestogen percutaneous ointment preparation method: natural progestogen and penetration enhancer are dissolved in oil phase or aqueous phase, oil phase and water are heated to 70～85 ℃ respectively, keep 30min, the emulsifying pot is preheated to 70～85 ℃, evacuation.The water of elder generation's suction 3/4; Start emulsifying pot and stirring, behind the whole oil phases of suction, remaining 1/4 water of suction.Mixing and emulsifying 5～8min stirs and is cooled to room temperature, storage, fill.
(2) natural progestogen paster preparation method: at first be the modulation of medicine glue, be about to natural estrogen 1～1.5mg, norethindrone acetate 1～1.5mg and natural penetration enhancer 1～1.5mg and under 55 ℃, mix stirring 3～8min, guarantee the homogeneity of medicine glue.Adding polypropene pressure sensitive adhesive substrate such as PEG400 were stirred 0.5～2 hour, add the glue that is used as medicine again and stirred 2～4 hours, medicine glue is uniformly coated on the impervious plastic-aluminum of medicine is taken out after multiple 5～20 minutes, make paster.
(3) natural progestogen liposome gel preparation method: take by weighing each component (phospholipid, cholesterol, vitamin E and natural progestogen) by prescription, be dissolved in 20～40mlCHCl
3Film forming is done in middle rotary evaporation (40～50 ℃) volatilization, the phosphate buffered solution that will contain vitamin C 2～5mg, PVP30～40ml adds wherein, add tween 80 0.2～0.5ml simultaneously, behind rotary evaporation 4～6min, be interrupted ultrasonic 4～6min and form the natural progestogen liposome.
Take by weighing Carbopol-940 200～300mg and glycerol 4～6ml moistening grinds well, join in the liposome of making as stated above, the phosphate buffered solution that adds 2～4ml, after stirring swelling 2h, add 2～4ml triethanolamine, regulate pH to 6～7, add phosphate buffer solution at last to 50g, stir, promptly get the progesterone liposome gel.
(4) natural progestogen microcapsule preparation method: natural progestogen is dissolved in the penetration enhancer by mass fraction at 1: 1 mixes stirring with 3% sodium alginate soln 135ml, 7000～8000 rev/mins of rotating speeds, add 300～400 rev/mins of 3% aqueous gelatin solution, 120～150ml rotating speeds, emulsifying 8～10 minutes.
Being cooled to room temperature accent pH is 4.5～6.5, stirs 15～25 minutes with 300～400 rev/mins again, then is cooled to 5～10 ℃, and 80～100 rev/mins of stirrings.Liquid coolant is evenly splashed in the 0.25mol/l calcium chloride water, and the surface forms gel at once and generates slick microsphere.Treat all cohesions after washing filtering, the microsphere that obtains having certain intensity.
IV advantage of the present invention is:
The physiological function of natural progestogen is to suppress uterine contraction, and help endometrium to transform to the secretory phase by proliferative phase, be mainly used in diseases such as preventing miscarriage, treat amenorrhea, dysfunctional uterine hemorrhage, endometriosis, carcinoma of endometrium clinically, it is one of gynecological's medicine commonly used, consumption is big, the course of treatment is long, generally needs the 2 thoughtful several months of continuous application.
At present clinical widely use wide in variety is artificial synthetic progestin, cheap, biological activity is high, but because the first pass effect of its liver and slight androgenic activity, lipid metabolism, carbohydrate metabolism there is harmful effect, and edema, headache are arranged, feel sick, acne, cause side effect such as embryo's deformity, there is more restriction in clinical use.
The natural progestogen injection in clinical practice for many years can not the withstand prolonged intramuscular injection but the patient is many, is difficult to prolonged application.Oral natural progestogen bioavailability is very poor, and dosage also requires very big, is about 5～10 times of injected dose.
The present invention makes the progestin preparation that absorbs through skin with natural progestogen and natural penetration enhancer, given prominence to the characteristic of pure natural and plant vector, can avoid liver metabolic effect and gastrointestinal disorders for the first time, improve the utilization rate and the physiological function of giving full play to natural progestogen of natural progestogen, easy to use, safe, effective a kind of Therapeutic Method can be used for substituting oral progestogen and natural progestogen injection.
The IV zoopery
Experiment material: laboratory animal provides by central laboratory of Peking University First Hospital animal is real.Sample natural progestogen percutaneous preparation of the present invention is provided by plant research exploitation Beijing key lab of Beijing Technology and Business University.Progestogen are measured and are adopted chemoluminescence method (U.S. DPC reagent).Pathological section adopts HE dyeing, reads sheet by Pathology Deparment of Peking University First Hospital.
Experimental technique: this experiment is divided into three parts.
The level of progesterone in the blood behind first's use sample of the present invention: 12 Wista rats are divided into two groups of A, B after the operation castration at random.A group progestogen consumption is 5.01mg/kg, and the B group is the blank group, and coating is 7 days continuously, and the last coating is taken a blood sample after 24 hours and surveyed progesterone level.
Second portion is measured the blood drug level when using sample of the present invention continuously, and observation endometrium morphological change: 5 of immaturity does, give sample 5.01mg/kg5 of the present invention days after the percutaneous complementing estrogen, got blood in 24 hours in the last administration and survey its progesterone level, dissect and to get the uterus and observe its inner membrance secretion degree.
The time of third part single-dose peak value and the morphologic relation of endometrium: 6 of immaturity does, give sample of the present invention once after the percutaneous complementing estrogen, per two is one group, got blood respectively at 24 hours, 48 hours, 72 hours and also put to death, survey its progesterone level and observe the endometrial secretion degree.
Experimental result
First: A group female rats body weight 175.00 ± 5.00g, progesterone 23.20 ± 15.35ng/ml.B group body weight 168.67 ± 7.63g, progesterone does not detect.
Second portion: immaturity doe body weight 738 ± 143.77g, progesterone level 9.38 ± 3.67ng/ml, 3 grades of inner membrance Mcphail indexes point out sample of the present invention to make female Sanguis Leporis seu oryctolagi progesterone reach level luteal phase, and inner membrance presents obvious secretory phase variation.
Third part: the 1st group of average weight 705.00g, average sample 2.35g of the present invention, progesterone average 1.1ng/ml, 1 grade of inner membrance Mcphail index; The 2nd group of average weight 775.00g on average uses sample 2.55g of the present invention, progesterone average 2.85ng/ml, 2 grades of inner membrance Mcphail indexes; The 3rd group of average weight 730.00g on average uses sample 2.43g of the present invention, progesterone average 0.31ng/ml, 3 grades of inner membrance Mcphail indexes. and about 48 hours peakings of single percutaneous dosing are described, endometrial influence is prolonged about 24 hours.
The specific embodiment
Embodiment 1:
Estradiol benzoate percutaneous ointment
Composition weight (%)
White oil 25.0
Olive oil 28.0
Vaseline 2.0
Lanoline 2.0
Soybean phospholipid 2.2
Butyl stearate 8.0
Borneolum Syntheticum 8.0
Estradiol benzoate 5.0
Tween 80 3.0
Glycerol 3.0
Tert-butyl group hydroxyanisol is an amount of
Methyl hydroxybenzoate is an amount of
The deionized water surplus
Preparation method: in the water pot, under the stirring condition, add deionized water, glycerol, tween 80 and methyl hydroxybenzoate, the insulation of dissolving back, froth breaking are 10 minutes fully.
Estradiol benzoate, Borneolum Syntheticum, olive oil, vaseline, lanoline, soybean phospholipid, butyl stearate are added in the oil phase pot, stir down temperature is risen to 85 ℃, be incubated 10 minutes.The emulsifying pot is preheated to 85 ℃, evacuation.The water of elder generation's suction 3/4; Start in the emulsifying pot and stir, behind the whole oil phases of suction, remaining 1/4 water of suction.Close stirring, start homogenizer (rotating speed 2500rpm), homogenizing 5 minutes.Start stirring (rotating speed 20rpm), keep 85 ℃ of kettle temperatures, cooling after 10 minutes.Add the tert-butyl group hydroxyanisol when temperature is reduced to 48 ℃, continue cooling, stirred at least 30 minutes, temperature is filtered discharging at 120 order drainage screens below 35 ℃.
Embodiment 2
Conjugated estrogen hormone percutaneous ointment
Composition weight (%)
Monoglyceride 3.0
Mixed alcohol 5.0
Silicone oil 6.0
Isopropyl palmitate 2.0
Aloe 1.5
Glycerol 5.0
Propylene glycol 2.0
Tween 80 1.5
EDTA-2Na 0.1
Triethanolamine 0.1
Conjugated estrogen hormone 10.0
Aloe original juice adds to 100
Embodiment 3
The natural progestogen paster
Medicine glue modulated process: medicine glue conditioning agent formulation: every subsides contain 17 beta estradiol 1mg, norethindrone acetate 1mg and Mentholum 1mg.In the medicine glue modulated process, the glue refining temperature is 55 ℃, stirs 5min, guarantees the homogeneity of medicine glue.Adding polypropene pressure sensitive adhesive substrate such as PEG400 were stirred 1 hour, add the glue that is used as medicine again and stirred 3 hours, medicine glue is uniformly coated on the impervious plastic-aluminum of medicine is taken out after multiple 15 minutes, make paster.
Embodiment 4
The progesterone liposome gel
Accurate weighing phosphatidase 15 00mg, cholesterol 200mg, vitamin e1 0mg, progesterone 20mg is dissolved in 35mlCHCl
3Film forming is done in middle rotary evaporation (45 ℃) volatilization, will contain an amount of 36ml phosphate buffered solution (PBS) of vitamin C 3mg, PVP and add wherein, adds tween 80 0.4ml simultaneously, behind the rotary evaporation 5min, is interrupted ultrasonic 5min and forms liposome.
Take by weighing Carbopol-940 250mg and the moistening of 4ml glycerol grinds well, join in the liposome of making as stated above, add the PBS of 3ml, after stirring swelling 2h, add the 2ml triethanolamine, regulate pH to 6～7, add PBS to 50g at last, stir, promptly get the progesterone liposome gel.
Embodiment 5
The progesterone microcapsule
Progesterone 15mg is dissolved in the 15ml Oleum Eucalypti mixes stirring with 3% sodium alginate soln 135ml, 7500 rev/mins of rotating speeds add 350 rev/mins of 3% aqueous gelatin solution 140ml rotating speeds, emulsifying 10 minutes.
Being cooled to room temperature accent pH is 5.5, stirs 20 minutes with 350 rev/mins again, then is cooled to 5～10 ℃, and stirs at a slow speed.Liquid coolant is evenly splashed in the 0.25mol/l calcium chloride water, and the surface forms gel at once and generates slick microsphere.Treat all cohesions after washing filtering, the microsphere that obtains having certain intensity.
Claims (8)
1. a natural progestogen percutaneous preparation is characterized in that, contains the composition of following weight ratio:
Natural progestogen 5～40wt%
Penetration enhancer 40～60wt%
2. natural progestogen percutaneous preparation according to claim 1 is characterized in that: described natural progestogen is one or more in conjugated estrogen hormone, estradiol valerate, estradiol benzoate, estradiol cypionate, the progesterone.
3. natural progestogen percutaneous preparation according to claim 1 is characterized in that: described penetration enhancer is one or more in book lotus brain, Borneolum Syntheticum, Oleum Eucalypti, Rhizoma Chuanxiong, Elettaria cardamomum (L.) Maton, the Aloe extract.
4. natural progestogen percutaneous preparation according to claim 1 is characterized in that, can be mastic, the subsides of percutaneous skin, liposome and microcapsule.
5. the preparation method of a natural progestogen percutaneous mastic is characterized in that: natural progestogen and penetration enhancer are dissolved in oil phase or aqueous phase, oil phase and water are heated to 70～85 ℃ respectively, keep 30min, the emulsifying pot is preheated to 70～85 ℃, evacuation; The water of elder generation's suction 3/4; Start emulsifying pot and stirring, behind the whole oil phases of suction, remaining 1/4 water of suction; Mixing and emulsifying 5～8min stirs and is cooled to room temperature, and storage, fill are promptly.
6. the preparation method that natural progestogen percutaneous skin pastes is characterized in that: natural estrogen 1～1.5mg, norethindrone acetate 1～1.5mg and natural penetration enhancer 1～1.5mg are mixed stirring 3～8min under 55 ℃, guarantee the homogeneity of medicine glue; Adding polypropene pressure sensitive adhesive substrate such as PEG400 were stirred 0.5～2 hour, add the glue that is used as medicine again and stirred 2～4 hours, medicine glue is uniformly coated on the impervious plastic-aluminum of medicine is taken out after multiple 5～20 minutes, make paster.
7. the preparation method of a natural progestogen percutaneous liposome is characterized in that: each component is dissolved in 20～40mlCHCl
3Middle rotary evaporation, do film forming 40～50 ℃ of volatilizations, will contain vitamin C 2～5mg, PVP30～40ml phosphate buffered solution and add wherein, add tween 80 0.2～0.5ml simultaneously, behind rotary evaporation 4～6min, be interrupted ultrasonic 4～6min and form the natural progestogen liposome; Take by weighing Carbopol-940200～300mg and glycerol 4～6ml moistening grinds well, join in the liposome of making as stated above, the phosphate buffered solution that adds 2～4ml, after stirring swelling 2h, add 2～4ml triethanolamine, regulate pH to 6～7, add phosphate buffer solution at last to 50g, stir, promptly get the progesterone liposome gel.
8. the preparation method of a natural progestogen percutaneous microcapsule, it is characterized in that: natural progestogen is dissolved in the penetration enhancer by mass fraction at 1: 1 mixes stirring with 3% sodium alginate soln 135ml, 7000～8000 rev/mins of rotating speeds, add 300～400 rev/mins of 3% aqueous gelatin solution, 120～150ml rotating speeds, emulsifying 8～10 minutes; Being cooled to room temperature accent pH is 4.5～6.5, stirs 15～25 minutes with 300～400 rev/mins again, then is cooled to 5～10 ℃, and 80～100 rev/mins of stirrings; Liquid coolant is evenly splashed in the 0.25mol/l calcium chloride water, and the surface forms gel at once and generates slick microsphere; Treat all cohesions after washing filtering, the percutaneous microcapsule that obtains having certain intensity.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102397255A (en) * | 2011-11-24 | 2012-04-04 | 广东药学院 | Progesterone ethosome, and preparation method and application thereof |
| CN102652733A (en) * | 2012-04-29 | 2012-09-05 | 新疆维吾尔自治区包虫病临床研究所 | Natural progesterone proliposome preparation and preparation method and using method thereof |
-
2003
- 2003-11-28 CN CNA2003101169042A patent/CN1546043A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102397255A (en) * | 2011-11-24 | 2012-04-04 | 广东药学院 | Progesterone ethosome, and preparation method and application thereof |
| CN102397255B (en) * | 2011-11-24 | 2013-06-26 | 广东药学院 | Progesterone ethosome, and preparation method and application thereof |
| CN102652733A (en) * | 2012-04-29 | 2012-09-05 | 新疆维吾尔自治区包虫病临床研究所 | Natural progesterone proliposome preparation and preparation method and using method thereof |
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