CN1310615A - Estradiol-containing patch for transdermal administration of hormones - Google Patents

Estradiol-containing patch for transdermal administration of hormones Download PDF

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Publication number
CN1310615A
CN1310615A CN99808853A CN99808853A CN1310615A CN 1310615 A CN1310615 A CN 1310615A CN 99808853 A CN99808853 A CN 99808853A CN 99808853 A CN99808853 A CN 99808853A CN 1310615 A CN1310615 A CN 1310615A
Authority
CN
China
Prior art keywords
active substance
paster
comprises active
stock
pressure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN99808853A
Other languages
Chinese (zh)
Inventor
艾维拉·克斯特根
瑞候德·梅克尼
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie Systeme AG
Original Assignee
LTS Lohmann Therapie Systeme AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LTS Lohmann Therapie Systeme AG filed Critical LTS Lohmann Therapie Systeme AG
Publication of CN1310615A publication Critical patent/CN1310615A/en
Pending legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • 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
    • 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
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/58—Adhesives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/34—Gestagens

Abstract

The invention relates to a patch containing an active substance for controlling the release of estradiol or pharmaceutically acceptable derivatives thereof on its own or combined with gestagens into the human or animal skin, consisting of a back layer, a reservoir connected thereto containing an active substance and suitable for combined release thereof and having adhesive means and a removable protective layer. The invention is characterized in that the adhesive used contains cholesterol or corn starch.

Description

Use the paster that contains estradiol of hormone through skin
The present invention relates to a kind of paster that comprises active substance, this paster is in order to control estradiol or its pharmaceutically acceptable derivant, separately or with the compound skin that is released into the mankind or animal of gestogen.
The paster that comprises estrogen and/or gestogen is well-known.Yet they truly have shortcoming, because paster not only contains ethanol but also comprise the potential danger of active substance recrystallize during use.
Known estradiol and the ethanol of in a kind of prescription of paster, using simultaneously from DE-OS 32 05 258 and EP 0 285 563.Yet it is very complicated to make this paster, and this paster is not too comfortable after being used, because their lack pliability.
EP 0 285 563 describes the dermally treating system of a kind of estrogen and the compound use of gestogen.Its stock comprises active matter formula and selectable a kind of film, and ethanol is as the absorption enhancer via skin.Because active substance discharges mainly by film control, this dermally treating system fundamentally is different from active substance paster of the present invention.The described paster of document thus, the function of adhesive just fixedly paster on skin.Non-its main task of release of control active substance, and be a kind of side effect that may be unnecessary.This paster is so-called " bag shape paster (pouch patch) ", because of its active matter formula is present in the satchel, is made of a kind of impermeable back pad layer and the film with bonding coat.Because the cause of its labyrinth, making this paster needs high cost, because indivedual composition must prepare respectively, then in follow-up method step, in conjunction with to form a paster.
EP 0 275 716 describes a kind of endermic two-layer system and compares with single-layer system of the present invention and use one or more estrogen simultaneously, this estrogen dissolving or little being scattered in the polymeric layer.In this, varistor layer also comprises the material that can promote through the skin absorption except comprising the active ingredient beyond the region of objective existence.This polymer and varistor layer can be by polyacrylic acid lipids, and type siloxane or polyisobutylene class are formed.
EP 0,328 806 describes a kind of dermally treating system that does not have film, its substrate by polyacrylate adhesive, solvent, penetration enhancers and estrogen and derivant thereof with and combination and forming.
WO 87/07138 describes a kind of estradiol patch, and this paster comprises the back pad layer, comprises the substrate and the pressure-sensitive cement of active substance, and this adhesive is covered by removable protective layer.The production of this substrate and pressure-sensitive cement is according to the viewpoint of application technology, need in the method step of high cost very, carry out, promptly through homogenizing, outgas, apply, dry and be divided into discrete fragment.In one embodiment, this back pad layer must apply equably with pressure-sensitive cement, promptly means follow-up method step.Various piece is combined in other method step of branch carries out.Therefore the integral production of paster comprises high cost and complexity.
From US 4 624 665, known packets is contained in the stock system with the active substance of little coating form.This stock is embedded between back pad layer and the film.The skin of this system provides a kind of pressure-sensitive cement.The structure of this system and production are very complicated, because active substance must distribute by little coating and with homogeneous phase, then, in subsequent method step, must be embedded between back pad layer and the film.In addition, this system must provide a kind of pasting together of boundaries and apply layer protective layer.
In addition, known activity patch from EP 0 186 019 wherein is added into the water-swellable polymer, and can discharges estradiol from this paster in rubber/binder resin material.Yet, it reveals be the estradiol that from these active substance pasters, discharges very little and can not meet the demand of treatment.
In DE-OS 20 06 696, a kind of paster or a kind of adhesion binder are described, it have the effect of general and wherein contraceptive substance be impregnated in and bind composition or bind in the thin film.It can be a kind of acrylate that this kind binds thin film.
Therefore the shortcoming that the objective of the invention is to avoid above-mentioned provides a kind of stable, does not promptly have recrystallize, includes the paster of estrogen and/or gestogen, and this paster has enough active substances and discharges, and this release is not stored and changed.
Surprisingly, a kind of pressure-sensitive cement that comprises estrogen and/or gestogen can be reached this purpose, and this pressure-sensitive cement comprises cholesterol or corn starch.
Therefore, can achieve the above object by the described paster that comprises active substance of main claim.These appended claims relate to the preferred especially specific embodiments of the present invention.
Cholesterol is considered to a kind of medical material and is described in as in the pharmacopeia.Cholesterol is regulated material and conduct protection material as a kind of swelling.The reason of using it is that skin has good tolerance to it, because it makes epidermis soft and smooth.In addition, its absorbability that can moisturize.
Corn starch also has description in pharmacopeia.The use corn starch is tackifying ability and the absorbability because of it, and its swelling ability.
Active substance paster according to the present invention can be used for cosmetics, and is used for the mankind or veterinary's therapeutic purposes.
Have the paster that contains no recrystallize estrogen and/or gestogen that enough active substances discharges, comprise estradiol and pharmaceutically acceptable derivant, independent or compound thereof in its stock with gestogen, its concentration is 1 to 20% (weight) with respect to stock composition total amount, and being actually is 1: 1 to 1: 10 mol ratio.
This stock that comprises estradiol can comprise at least a composition and be selected from the age resistor class, plasticizer class, antioxidant class and absorption enhancer class.Suitable plasticizer class is that those of skill in the art are known in this area, and is for example narrating among the DE 37 43 946.This contains the estradiol stock and comprises plasticizer class up to 5% (weight) usually.
In addition, this stock comprises the age resistor class of concentration up to 1% (weight).These are that those of skill in the art are known in this area, and are for example narrating among the DE 37 43 946.
Impermeable back pad layer and departing protective layer material are known by those of skill in the art in this area.
Containing the estradiol stock can be by solution, dispersion liquid and melt manufacturing.
If this stock does not have enough intrinsic tacknesss to skin, the pressure-sensitive cement of additional non-activity material can be provided or provide around the pressure-sensitive cement edge.Can guarantee that by this way endermic paster can continue to stick together on skin between the whole operating period.
A kind of particularly preferred estradiol that contains is a kind of matrix system through the structure of skin paster, and wherein, known this kind substrate controls all the time that active substance discharges and according to the Vt law of Higuchi.Yet this does not represent that the film system does not have advantage for special circumstances.In the film system, the film of sustained release active substance is between stock and pressure sensitive adhesion layer.
Depend on the needs in the treatment and can correspondingly adjust through the thickness of skin paster.Usually, its scope is from 0.03 to 0.6 millimeter.
The present invention will be illustrated by following specific embodiment.
Embodiment 1:
131.91 gram Durotak 387-2287 solution (solid matters of 67.8 grams), 3.2 gram cholesterol, 55.89 gram ethanol/ethyl acetate (2: 1 gram/grams) are at room temperature stirred and homogenize.Subsequently, add 2.0 gram beta-Estradiol hemihydrates and 7.0 gram norethindrone acetates and stirring about two hours.
The bonding material that contains active substance that generates is coated in departing protective layer (Hostaphan RN 100 has one side with silicone coating, is to utilize Hoechst Diafoil) to be gone up to cause the about 80 gram/rice of the weight that contains active substance stock per unit area 2Product.The obstructed permeable back pad layer of lamination (mylar, thickness are 19 microns) on this stock.Stamp out 16 centimetres subsequently 2The active substance paster.
Embodiment 2:
131.91 gram Durotak 387-2287 solution (solids of 67.8 grams), 3.2 gram corn starchs and 55.89 gram ethanol/ethyl acetate (2: 1 gram/grams) are at room temperature stirred homogenize.Add 2.0 gram beta-Estradiol hemihydrates and 7.0 gram norethindrone acetates and stirring subsequently about two hours.
The bonding material that contains active substance that generates is coated in departing protective layer (Hostaphan RN 100; one side being arranged with silicone coating, is to utilize Hoechst Diafoil) go up that to contain the weight that the active substance stock has per unit area approximately be 80 gram/rice to cause 2Product.The impermeable back pad layer of lamination (mylar, thickness are 19 microns) on this stock.Stamp out 16 centimetres subsequently 2The active substance paster.
In order to measure the permeability of human skin, skin is clamped down on becomes French Franc cell (Franzcell) now.A kind of have 1.539 centimetres 2The paster that contains estrogen and/or gestogen on surface is attached on the skin, and in 37 ℃ of releases (acceptor medium: 0.9% sodium chloride solution adds 0.1% Hydrazoic acid,sodium salt) of measuring active substance down.
Detection recrystallize phenomenon ties up in the backlight carries out.
It the results are shown in table 1
Table 1: analysis result
Embodiment Activity substance content microgram/16 centimetre 2Es????????????????NeA Human skin permeability microgram/16 centimetres 2(24-48 hour) Es NeA Recrystallize
?1 ?2 ?3.200 ?3.200 ?11.200 ?11.200 ?97 ?173 ?131 ?163 Do not have
Comparative product Evorel Conti ?3.200 ?11.200 ?33 ?46 Merit attention
Es: beta-Estradiol hemihydrate
NeA: norethindrone acetate
It is as shown in the table, and paster according to the present invention is compared with comparative product, infiltrates through human being significantly improved.Simultaneously confirmable is not have the recrystallize phenomenon to take place according to embodiments of the invention.

Claims (14)

1. paster that comprises active substance; this paster is in order to control estradiol or its pharmaceutically acceptable derivant; separately or with the compound skin that is released into the mankind or animal of gestogen; this paster by the back pad layer, connect on it and to be fit in conjunction with the release of active substance and to utilize the stock that comprises active substance and the departing protective layer of pressure-sensitive cement manufacturing to be formed, it is characterized in that this pressure-sensitive cement includes cholesterol or corn starch.
2. according to the paster that comprises active substance of claim 1, it is characterized in that this stock comprises the cholesterol of 1-30% (weight) and the corn starch of 1-20% (weight).
3. according to the paster that comprises active substance of claim 1, it is characterized in that this stock comprises estradiol or its pharmaceutically acceptable derivant, independent or compound with gestogen, its amount is 1-20% (weight), is preferably 1.5-15% (weight).
4. according to the paster that comprises active substance of claim 1 or 3, it is characterized in that this stock comprises estradiol or its pharmaceutically acceptable derivant, independent or compound with gestogen, its mol ratio is 1: 1 to 1: 10.
5. according to each the paster that comprises active substance of claim 1 to 4, it is characterized in that it is the tackifying resin of 1-50% (weight) that this pressure-sensitive cement comprises concentration.
6. according to one or the multinomial paster that comprises active substance of claim 1 to 5, it is characterized in that this stock comprises at least a composition and is selected from the age resistor class, antioxidant class and absorption enhancer class.
7. according to one or the multinomial paster that comprises active substance of claim 1 to 6, it is characterized in that this pressure-sensitive cement is a kind of pressure-sensitive solution adhesive, pressure-sensitive dispersion liquid adhesive or hot-melt pressure sensitive adhesive.
8. according to one or the multinomial paster that comprises active substance of claim 1 to 7, it is characterized in that this back pad layer is impermeable for the composition of stock.
9. according to one or the multinomial paster that comprises active substance of claim 1 to 8, it is characterized in that this stock is made up of multilamellar and the additional pressure-sensitive cement layer that comprises active substance is provided.
10. according to one or the multinomial paster that comprises active substance of claim 1 to 9, the film that it is characterized in that the sustained release active substance is between stock and pressure-sensitive cement layer.
11., it is characterized in that this stock provides a kind of around the pressure-sensitive cement limit according to or the multinomial paster that comprises active substance of claim 1 to 10.
12. according to one or the multinomial paster that comprises active substance of claim 1 to 11, the thickness range that it is characterized in that the paster that this comprises active substance is between 0.03 to 0.6 millimeter.
13., be used for making up according to the paster that comprises active substance of claim 1 to 12.
14., be used to prepare the medicine of the mankind or veterinary treatment purpose according to one the paster that comprises active substance of claim 1 to 12.
CN99808853A 1998-07-29 1999-07-16 Estradiol-containing patch for transdermal administration of hormones Pending CN1310615A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19834006A DE19834006A1 (en) 1998-07-29 1998-07-29 Estradiol-containing patch for the transdermal application of hormones
DE19834006.0 1998-07-29

Publications (1)

Publication Number Publication Date
CN1310615A true CN1310615A (en) 2001-08-29

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Family Applications (1)

Application Number Title Priority Date Filing Date
CN99808853A Pending CN1310615A (en) 1998-07-29 1999-07-16 Estradiol-containing patch for transdermal administration of hormones

Country Status (14)

Country Link
EP (1) EP1100478A1 (en)
JP (1) JP2002521426A (en)
KR (1) KR20010072071A (en)
CN (1) CN1310615A (en)
AR (1) AR019948A1 (en)
AU (1) AU762589B2 (en)
BR (1) BR9912688A (en)
CA (1) CA2338861A1 (en)
DE (1) DE19834006A1 (en)
IL (1) IL141032A0 (en)
PL (1) PL345696A1 (en)
TR (1) TR200100290T2 (en)
WO (1) WO2000006130A1 (en)
ZA (1) ZA200100721B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005047906A (en) * 2003-07-16 2005-02-24 Taisho Pharmaceut Co Ltd Anti-inflammatory/analgesic composition for external application
KR100689534B1 (en) * 2005-05-18 2007-03-02 삼성전자주식회사 Mobile phone

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH674618A5 (en) * 1987-04-02 1990-06-29 Ciba Geigy Ag
DE4210711A1 (en) * 1991-10-31 1993-05-06 Schering Ag Berlin Und Bergkamen, 1000 Berlin, De TRANSDERMAL THERAPEUTIC SYSTEMS WITH CRYSTALIZATION INHIBITORS
US5676968A (en) * 1991-10-31 1997-10-14 Schering Aktiengesellschaft Transdermal therapeutic systems with crystallization inhibitors
DE4229820C2 (en) * 1992-09-07 1998-12-03 Jenapharm Gmbh Progestogen-based pharmaceutical preparation
WO1995017896A1 (en) * 1993-12-27 1995-07-06 Akzo Nobel N.V. Percutaneously absorbable preparation
DE4416927C1 (en) * 1994-05-13 1995-08-31 Lohmann Therapie Syst Lts Device for release of active agents from melt-type adhesive

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Publication number Publication date
JP2002521426A (en) 2002-07-16
AU5284299A (en) 2000-02-21
ZA200100721B (en) 2002-05-27
IL141032A0 (en) 2002-02-10
DE19834006A1 (en) 2000-02-24
PL345696A1 (en) 2002-01-02
TR200100290T2 (en) 2001-07-23
BR9912688A (en) 2001-11-27
AU762589B2 (en) 2003-06-26
CA2338861A1 (en) 2000-02-10
KR20010072071A (en) 2001-07-31
WO2000006130A1 (en) 2000-02-10
EP1100478A1 (en) 2001-05-23
AR019948A1 (en) 2002-03-27

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