CN103830207A - Lasofoxifene tartrate emplastrum - Google Patents
Lasofoxifene tartrate emplastrum Download PDFInfo
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- CN103830207A CN103830207A CN201410093535.8A CN201410093535A CN103830207A CN 103830207 A CN103830207 A CN 103830207A CN 201410093535 A CN201410093535 A CN 201410093535A CN 103830207 A CN103830207 A CN 103830207A
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Abstract
The invention discloses a lasofoxifene tartrate emplastrum preparation and a preparation method for the same. According to the preparation method disclosed by the invention, lasofoxifene tartrate micro-emulsion is prepared into a transdermal emplastrum, and the transdermal emplastrum is divided into four layers, that is, an anti-sticking layer, an adhesive layer, a backing layer and a medicine storage layer; the medicinal ingredient is lasofoxifene tartrate micro-emulsion, and is composed of lasofoxifene tartrate used as an active ingredient, polysorbate 80 used as a surfactant, propylene glycol used as a cosurfactant, pure water or distilled water and the like. Some non-polar polymers, a plasticizer, a tackifier, a transdermal accelerant and an antioxidant are further added in the emplastrum preparation disclosed by the invention besides the medicinal ingredients above. The lasofoxifene tartrate emplastrum preparation disclosed by the invention has the positive significance that compared with the existing dosage forms and tablets, the lasofoxifene tartrate emplastrum preparation has the prominent advantages of being lasting in efficacy, safe and low-toxicity, convenient, simple and sanitary to use, and accurate in medication dose.
Description
Invention field
The present invention relates to chemical pharmacy field, be specifically related to a kind of lasofoxifene tartrate emplastrum.
Background of invention
Since nearly over half a century, the quality of life problem that improves menopausal women more and more receives publicity, and hormone replacement therapy (HRT) has been widely used in climacteric and postmenopausal women.Although accumulated Observational data evidence for many years, in healthy menopausal women, use the pros and cons problem of HRT still among inquiring into.People, on the one hand in the more scientific more rational HRT scheme of further investigation, are applicable to the more preferably medicine of menopausal women on the one hand in searching.Selective estrogen receptor modulators (SERMS) is the medicine of a class synthetic, in some tissues, plays estrogen-like effects, plays the effect of estrogen antagonist sample in other tissues, is expected to for preventing and treating Menopausal diseases.Tamoxifen is first generation SERM, at mammary gland performance estrogenic antagonist, has been successfully used to the auxiliary treatment of breast carcinoma, but endometrium is had to stimulation.Lasofoxifene tartrate (lasofoxifene tartrate) is second filial generation SERM, to bone and Cardiovasculai appearance in patient estrogen-like effects, and at uterus and mammary gland performance estrogenic antagonist, has better potential applicability in clinical practice.
Osteoporosis chief reason is calcareous from skeletal tissue's loss, makes skeleton bulking, becomes fragile, dies down, thereby easily fracture.After women's menolipsis, may reduce because of estrogenic synthetic quantity, and osteoporosis easily occurs.The fracture of its Chang Bingfa vertebra, wrist and hip, and can increase and aggravation along with the age.
Lasofoxifene tartrate (lasofoxifene tartrate), chemistry (5R by name, 6S)-5,6,7,8-tetrahydrochysene-6-phenyl-5-[4-[2-(l-pyrrolidinyl) ethyoxyl] phenyl]-beta naphthal (2S, 3S)-tartrate, be the selective estrogen receptor modulators of Pfizer Inc.'s research and development, in April, 2009, its commercial tablets was called Fablyn in Europe approval listing.This product presents selectivity excitement or antagonism in different estrogen target tissues, and female sharp receptor ER α and ER β are had to affinity highly, the clinical postmenopausal osteoporosis that is used for the treatment of.Its structural formula is as shown in the formula shown in (I):
-as in situation, lasofoxifene tartrate oral formulations can be by fine tolerance, common side reaction is hectic fever and lower limb spasm, the most serious side reaction is venous thromboembolism, the toxicity of medicine has damage to a certain degree to liver function simultaneously.Lasofoxifene tartrate microemulsion formulation has good transdermal effect and slow release, targeting, simultaneously, the structure of microemulsion has been isolated contacting of extraneous and medicine, can prevent oxidation of drug and hydrolysis, improve stability, cover bad smell, the holding time extends, preparation technology is simple, does not need special installation.But, the administration time that external preparation need to be longer, the open-assembly time of agents area is too short, and transdermal effect may not reach requirement, covers with medicated clothing, easily wipes medicine, pollution clothes; Meanwhile, the dosage of microemulsion formulation is also difficult to control.
In order to keep the therapeutic effect that lasofoxifene tartrate is good, overcome deficiency, special microemulsion plaster (Microemulsion) new technique of introducing, develops into lasofoxifene tartrate microemulsion emplastrum.
Summary of the invention
The invention provides a kind of new lasofoxifene tartrate emplastrum, preparation technology is simple, and can make it keep good therapeutic effect, and compare as tablet with existing dosage form, there is lasting medicine, safety and low toxicity, health simple and easy to use, dosage outstanding advantages accurately.
On the one hand, the invention provides a kind of lasofoxifene tartrate emplastrum, it is made up of lasofoxifene tartrate microemulsion and pharmaceutically acceptable adjuvant, be divided into adherent layer, adhered layer, drug storing layer and four parts of backing layer, wherein, drug storing layer is lasofoxifene tartrate microemulsion, and adherent layer, adhered layer and backing layer three parts are to be prepared by pharmaceutically acceptable adjuvant.
Some embodiments therein, lasofoxifene tartrate emplastrum of the present invention, wherein said pharmaceutically acceptable adjuvant is one or more in non-polar polymer, plasticizer, viscosifier, transdermal enhancer and antioxidant.
In other embodiments, lasofoxifene tartrate emplastrum of the present invention, wherein pharmaceutically acceptable adjuvant is as the polysorbate 80 of surfactant, as cosurfactant propylene glycol, as one or more in oleic acid and Acritamer 940 and pure water or the distilled water of cosolvent.
Some embodiments therein, lasofoxifene tartrate emplastrum of the present invention, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.1%-5%, polysorbate 10%-50%, propylene glycol 10%-60%, oleic acid 0.1%-20%, pure water or distilled water 20%-80%.
In other embodiments, lasofoxifene tartrate emplastrum of the present invention, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.5%-3%, polysorbate 10%-30%, propylene glycol 20%-50%, oleic acid 0.5%-10%, pure water or distilled water 30%-60%.
In other embodiments, lasofoxifene tartrate plaster preparation of the present invention, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.5%, polysorbate 15%, propylene glycol 30%, oleic acid 4.5%, pure water or distilled water 50%.
Some embodiments therein, lasofoxifene tartrate emplastrum of the present invention, wherein, described non-polar polymer is one or more in polyisobutylene, polystyrene, polyisoprene, polybutadiene, polyhexene-butylene, polyethylene-propylene, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, natural rubber and butyl rubber.
Some embodiments therein, lasofoxifene tartrate emplastrum of the present invention, wherein, described plasticizer is wherein one or more such as liquid paraffin, vaseline, long-chain fatty acid phthalate ester; Viscosifier can be wherein one or more of resinae, rosin based, esterase and hydrogenated ester; Transdermal enhancer is one or more in fatty acid, fatty alcohol, fatty acid ester, alkyl sulfoxide class, azone class, pyrrolidinone compounds, surfactant, carbamide class and limonene; Antioxidant is one or more in 2,6-di-t-butyl Pyrogentisinic Acid, antrancine 12 and vitamin E.
In emplastrum of the present invention, except above-mentioned active ingredient, also add some non-polar polymers, plasticizer, viscosifier, transdermal enhancer and antioxidant.Non-polar polymer can be one or more in polyisobutylene, polystyrene, polyisoprene, polybutadiene, polyhexene-butylene, polyethylene-propylene, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, natural rubber, butyl rubber; Plasticizer can be one or more in liquid paraffin, vaseline, long-chain fatty acid phthalate ester; Viscosifier can be one or more in resinae, rosin based, esterase, hydrogenated ester; Transdermal enhancer can be one or more in fatty acid, fatty alcohol, fatty acid ester, alkyl sulfoxide class, azone class, pyrrolidinone compounds, the neat U of surface activity, carbamide class, limonene and other fat-soluble transdermal enhancers; Antioxidant can be one or more in 2,6_ di-t-butyl Pyrogentisinic Acid, antrancine 12, vitamin E.
Lasofoxifene tartrate emplastrum of the present invention can be prepared through the following steps:
By lasofoxifene tartrate and mixed with propylene glycol, after heating for dissolving, add polysorbate 80, oleic acid, stir, then add pure water or distilled water, be stirred to transparency liquid, the lasofoxifene tartrate microemulsion obtaining is for subsequent use.Acceptable adjunct ingredient is heated to 140-160 DEG C of melting, cool the temperature to after 90-100 DEG C and add bonding force reinforcing agent and lasofoxifene tartrate microemulsion for subsequent use, mix, then by mixture while hot to stripping film (release paper), lid layer stripping film more above, two sides pressurization makes film forming.Above-mentioned film is to be cooled to room temperature, and one deck stripping film is peeled off above, and non-woven fabrics is covered on adhesive phase and pressurizes and form.
Positive effect of the present invention is, compares as tablet with existing dosage form, has advantages of following outstanding:
1. can maintain metastable local blood drug level, bring into play lasting drug effect, 24 hours accumulative total transdermal amounts of main component exceed 70%, can keep in a long time relatively constant blood drug level in part, not only avoid the peak valley phenomenon of the caused blood drug level of whole body administration, also can reduce administration number of times, be conducive to the treatment of disease.
2. effective ingredient, in skin enters body, directly acts on diseased region, can effectively avoid " first pass effect " and the gastrointestinal reaction of oral administration, has reduced the toxicity of medicine, has improved the safety of medication.
3. easy to use, simple, there is no the issuable difficulty of other dosage forms and misery, improve patient's adaptability.
4. the form that adopts emplastrum, not only dosage is accurate, not pollution clothes, it is in good time to occur in part, removes at any time plaster, reduces the incidence rate of medicine toxicity.
5. the production technology of emplastrum is simple, is easy to grasp, and both can, in factory's painting machine mass production, also can, in Preparation Room in Hospital limited production, be convenient to realize the production automation and sterile working.Preparation process, without dust, becomes cream material few compared with other preparation consumptions simultaneously, is conducive to save, and is conducive to environmental conservation and labor protection.
6. emplastrum volume is little, lightweight, packs, stores and transports, carries all more convenient.
7. while adopting different one-tenth cream materials, can make the emplastrum of different drug release rates and the emplastrum of multilamellar pastille, be conducive to solve the incompatibility that may occur between medicine.
Pharmaceutically acceptable adjuvant of the present invention comprises, but be not limited to, ion-exchanger, aluminum, aluminium stearate, lecithin, serum albumin, as human albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, the partial glycerol ester admixture of saturated vegetable fatty acid, water, salt or electrolyte, as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloid silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, polyethylene-polyoxypropylene-blocking-up polymer, lanoline, sugar, as lactose, dextrose plus saccharose, starch is as corn starch and potato starch, the derivant of cellulose and it is as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate, natural gum powder, Fructus Hordei Germinatus, gelatin, Pulvis Talci, adjuvant is as cocoa butter and suppository wax, oily as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum Sesami, olive oil, Semen Maydis oil and Oleum Glycines, glycols compound, as propylene glycol and Polyethylene Glycol, esters is as ethyl oleate and ethyl laurate, agar, buffer agent is as magnesium hydroxide and aluminium hydroxide, alginic acid, pyrogen-free water, Deng oozing salt, Lin Ge (family name) solution, ethanol, phosphate buffer solution, and other nontoxic proper lubrication agent are as sodium laurylsulfate and magnesium stearate, coloring agent, releasing agent, coating dress material, sweeting agent, flavoring agent and spice, antiseptic and antioxidant.
Pharmaceutical composition of the present invention can also optionally contain one or more diluent.The example of diluent comprises mannitol, sorbitol, biphosphate calcium dihydrate, microcrystalline Cellulose and efflorescence cellulose.Preferred diluent is microcrystalline Cellulose.Microcrystalline Cellulose can be obtained from several suppliers, comprises Avicel PH101, Avicel PH102, Avicel PH103, Avicel PH105 and Avicel PH200 that FMC Corporation manufactures.
Pharmaceutical composition of the present invention can also optionally contain disintegrating agent.Disintegrating agent can be the one in several modified starches, modified cellulose polymer or polycarboxylic acids, such as crosslinked Carboxymethyl cellulose sodium, Explotab, polacrilin potassium and calcium carboxymethylcellulose (CMCCalcium).In one embodiment, disintegrating agent is croscarmellose sodium.Croscarmellose sodium NF type A obtains with trade name " Ac-di-sol " on market.
Pharmaceutical composition of the present invention can also optionally contain one or more surfactants or wetting agent.Surfactant can be anion, cation or neutral surface active agent.Anion surfactant comprises sodium lauryl sulfate, dodecyl sodium sulfate, oleyl sodium sulfate and the sodium laurate mixing with stearate and Talcum.Cationic surfactant comprises benzalkonium chloride and alkyl trimethyl ammonium bromide.Neutral surface active agent comprises glycerol list olein, polyoxyethylene sorbitan fatty acid ester, polyvinyl alcohol and anhydro sorbitol fat.The embodiment of wetting agent comprises poloxamer, polyoxyethylene alkyl ether, castor oil derivatives and polyoxyethylene 8 stearate fat.
The present invention can also optionally join antioxidant in preparation, thereby gives its chemical stability.Antioxidant is selected from the extract of a-tocopherol, Y-tocopherol, S-tocopherol, tocopherol enrichment natural origin, sodium or calcium salt, the Vitamin C acyl cetylate of L-AA and it, amass wealth by heavy taxation propyl propionate, amass wealth by heavy taxation misery ester, amass wealth by heavy taxation sour dodecyl ester, Yoshinox BHT (BHT) and butylated hydroxyanisol (BHA).In one embodiment, antioxidant is BHT or BHA.
The present invention can also add sweeting agent and/or fumet.
Detailed description of the invention
Further explain the present invention below in conjunction with embodiment, but embodiment does not limit in any form to the present invention.
Embodiment 1.
Use this prescription, make lasofoxifene tartrate microemulsion for subsequent use.Acceptable adjunct ingredient is heated to 140-160 DEG C of melting, cool the temperature to after 90-100 DEG C and add bonding force reinforcing agent and lasofoxifene tartrate microemulsion for subsequent use, mix, then by mixture while hot to stripping film (release paper), lid layer stripping film more above, two sides pressurization makes film forming.Above-mentioned film is to be cooled to room temperature, and one deck stripping film is peeled off above, non-woven fabrics is covered to pressurize on adhesive phase form, and makes 1000.
Embodiment 2.
Use this prescription, make lasofoxifene tartrate microemulsion for subsequent use.Acceptable adjunct ingredient is heated to 140-160 DEG C of melting, cool the temperature to after 90-100 DEG C and add bonding force reinforcing agent and lasofoxifene tartrate microemulsion for subsequent use, mix, then by mixture while hot to stripping film (release paper), lid layer stripping film more above, two sides pressurization makes film forming.Above-mentioned film is to be cooled to room temperature, and one deck stripping film is peeled off above, non-woven fabrics is covered to pressurize on adhesive phase form, and makes 1000.
Embodiment 3.
Use this prescription, make lasofoxifene tartrate microemulsion for subsequent use.Acceptable adjunct ingredient is heated to 140-160 DEG C of melting, cool the temperature to after 90-100 DEG C and add bonding force reinforcing agent and lasofoxifene tartrate microemulsion for subsequent use, mix, then by mixture while hot to stripping film (release paper), lid layer stripping film more above, two sides pressurization makes film forming.Above-mentioned film is to be cooled to room temperature, and one deck stripping film is peeled off above, non-woven fabrics is covered to pressurize on adhesive phase form, and makes 1000.
Biologic test
Test 1 Thermodynamically stable experiment
The active ingredient of lasofoxifene tartrate emplastrum of the present invention is microemulsion, through 3000r/min centrifugal 30 minutes, and not stratified, do not precipitate, be still transparence, show that the lasofoxifene tartrate microemulsion of preparation is a thermodynamically stable dispersion.
Test particle diameter and the envelop rate of 2 active ingredient
Lasofoxifene tartrate emplastrum of the present invention, the particle diameter of active ingredient is between 20-100nm, and the envelop rate of medicine is more than 90%.
Test the transdermal test in vitro experiment of 3 emplastrumes
Investigate the transdermal absorption factor of the different exterior-applied formulations of lasofoxifene tartrate.Prepare respectively emplastrum, microemulsion, gel and the micro emulsion gels of lasofoxifene tartrate.The lasofoxifene tartrate content of four kinds of dosage forms is 0.5%.Adopt Franz transdermal diffusion instrument, rat skin of abdomen, 37 DEG C of normal saline are acceptable solution, respectively at the transdermal accumulative total infiltration capacity of measuring different time, as shown in table 1.
Transdermal absorption factor (the μ g/cm of table 1 lasofoxifene tartrate plaster dosage form
2.h) (n=4)
Through t testing identity, the transdermal penetration effect of microemulsion and micro emulsion gels, between the two without significant difference (P>0.05); The transdermal penetration effect of microemulsion and micro emulsion gels is significantly higher than gel (P<0.05); The transdermal penetration effect of emplastrum is significantly higher than micro emulsion gels, microemulsion and gel (P<0.05).
Test the stability experiment of 4 emplastrumes
Carry out such environmental effects experiment: the lasofoxifene tartrate emplastrum of packaging is placed on respectively under 60 DEG C of high temperature, high humidity 93%, illumination 45001x, 4 DEG C of conditions of low temperature and is deposited 10 days, investigate its character, discriminating, pH value, related substance, content, microbial limit, irritating property of skin, result indices before and after experiment has no significant change, and shows lasofoxifene tartrate emplastrum having good stability to influence factor.
Combine and accelerate experiment: the lasofoxifene tartrate emplastrum of packaging is placed in the environment of 40 DEG C of temperature and humidity 75% to 6 months.Investigate its character, discriminating, pH value, related substance, content, microbial limit, irritating property of skin, result indices before and after experiment has no significant change, and shows having good stability of lasofoxifene tartrate emplastrum.
Test irritating property of the skin experiment of 5 emplastrums
The part producing after the intact skin of observation animal and damaged skin multiple-contact lasofoxifene tartrate plaster irritates reaction.Test adopts consubstantiality left and right sides self-contrast method.9 rabbit are divided into 3 groups at random, 3 every group, are respectively intact skin low dose, heavy dose and vehicle group.In animal left side, lasofoxifene tartrate emplastrum (5mg/g and 20mg/g) and the each lg of plaster paste respectively in depilation district; Excipient lg is pasted in depilation district, right side.Every kind of tested material plaster area is 50cm
2trial zone, continuous 7 days.After last administration 24h, use warm water cleaning tested material, perusal and histopathologic examination, record plaster position and have or not erythema and edema situation, and observe plaster position and whether have the situations such as pigmentation, petechia, pachylosis or epidermatic atrophy, irritating property of skin intensity is evaluated.
Lasofoxifene tartrate plaster is to rabbit intact skin and repeatedly stimulation test result of damaged skin, during administration or observe for after drug withdrawal one week, all shows as without irritating property, changes without any other at plaster position, and average response value is less than 0.3, is without irritating property.
Test the skin anaphylactic test of 6 emplastrums
Repeat to contact after lasofoxifene tartrate plaster by animal skin, observe body immune system and react the performance on skin.Cavia porcellus is divided into five groups at random, 10 every group, male and female half and half.First group is blank group; Second group is vehicle group; The 3rd group is lasofoxifene tartrate emplastrum group; The 4th group is the plaster in lasofoxifene tartrate emplastrum, the 5th group of positive sensitizer 2,4-dinitro-chloro-benzene phenol.Paste each tested material lg in Cavia porcellus left side depilation district respectively, and repeated to apply ointment or plaster in the 7th day and 14 days, after last administration sensitization 14 days, each tested material is applied ointment or plaster respectively in depilation district, the right side of Cavia porcellus, after 6h, remove tested material, observe immediately, and in 24,48,72h observes respectively anaphylaxis.
Result of the test shows, positive drug 2, and 4-dinitro-chloro-benzene phenol makes animal occur anaphylaxis, and there are obvious erythema and Mild edema in tested district, all reaches 100% in 6h, 24h sensitization rate, is extreme sensitization.Blank group, vehicle group, lasofoxifene tartrate emplastrum group and lasofoxifene tartrate plaster group are exciting position without erythema, and without edema, without General Symptoms, sensitization rate is 0%.
Claims (8)
1. a lasofoxifene tartrate emplastrum, it is made up of lasofoxifene tartrate microemulsion and pharmaceutically acceptable adjuvant, be divided into adherent layer, adhered layer, drug storing layer and four parts of backing layer, wherein, drug storing layer is lasofoxifene tartrate microemulsion, and adherent layer, adhered layer and backing layer three parts are to be prepared from by pharmaceutically acceptable adjuvant.
2. lasofoxifene tartrate emplastrum according to claim 1, wherein said pharmaceutically acceptable adjuvant is one or more in non-polar polymer, plasticizer, viscosifier, transdermal enhancer and antioxidant.
3. lasofoxifene tartrate emplastrum according to claim 1, wherein pharmaceutically acceptable adjuvant is as the polysorbate 80 of surfactant, as cosurfactant propylene glycol, as one or more in oleic acid and Acritamer 940 and pure water or the distilled water of cosolvent.
4. according to the lasofoxifene tartrate emplastrum described in claim 1-3 any one, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.1%-5%, polysorbate 10%-50%, propylene glycol 10%-60%, oleic acid 0.1%-20%, pure water or distilled water 20%-80%.
5. lasofoxifene tartrate emplastrum according to claim 4, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.5%-3%, polysorbate 10%-30%, propylene glycol 20%-50%, oleic acid 0.5%-10%, pure water or distilled water 30%-60%.
6. lasofoxifene tartrate emplastrum according to claim 5, wherein, in described emplastrum, the percentage by weight of each composition in preparation is lasofoxifene tartrate 0.5%, polysorbate 15%, propylene glycol 30%, oleic acid 4.5%, pure water or distilled water 50%.
7. lasofoxifene tartrate emplastrum according to claim 2, wherein, described non-polar polymer is one or more in polyisobutylene, polystyrene, polyisoprene, polybutadiene, polyhexene-butylene, polyethylene-propylene, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, natural rubber and butyl rubber.
8. lasofoxifene tartrate emplastrum according to claim 2, wherein, described plasticizer is wherein one or more such as liquid paraffin, vaseline, long-chain fatty acid phthalate ester; Viscosifier can be wherein one or more of resinae, rosin based, esterase and hydrogenated ester; Transdermal enhancer is one or more in fatty acid, fatty alcohol, fatty acid ester, alkyl sulfoxide class, azone class, pyrrolidinone compounds, surfactant, carbamide class and limonene; Antioxidant is one or more in 2,6-di-t-butyl Pyrogentisinic Acid, antrancine 12 and vitamin E.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017201508A1 (en) * | 2016-05-20 | 2017-11-23 | Azure Biotech, Inc. | Vaginal delivery systems containing selective estrogen receptor modulator (serm) and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400897A (en) * | 2000-06-01 | 2003-03-05 | 沃特森药物公司 | Transdermal delivery LASOFOXIFENE |
| CN101700241A (en) * | 2009-11-06 | 2010-05-05 | 河南省生物工程技术研究中心 | Raloxifene emplastrum preparation and preparation method thereof |
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- 2014-03-14 CN CN201410093535.8A patent/CN103830207A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400897A (en) * | 2000-06-01 | 2003-03-05 | 沃特森药物公司 | Transdermal delivery LASOFOXIFENE |
| CN101700241A (en) * | 2009-11-06 | 2010-05-05 | 河南省生物工程技术研究中心 | Raloxifene emplastrum preparation and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017201508A1 (en) * | 2016-05-20 | 2017-11-23 | Azure Biotech, Inc. | Vaginal delivery systems containing selective estrogen receptor modulator (serm) and uses thereof |
| US10857127B2 (en) | 2016-05-20 | 2020-12-08 | Azure Biotech, Inc. | Vaginal delivery systems containing selective estrogen receptor modulator (SERM) and uses thereof |
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