EP1171091A1 - Preparations pharmaceutiques ou cosmetiques pour l'application locale intradermique d'hormones - Google Patents

Preparations pharmaceutiques ou cosmetiques pour l'application locale intradermique d'hormones

Info

Publication number
EP1171091A1
EP1171091A1 EP00926811A EP00926811A EP1171091A1 EP 1171091 A1 EP1171091 A1 EP 1171091A1 EP 00926811 A EP00926811 A EP 00926811A EP 00926811 A EP00926811 A EP 00926811A EP 1171091 A1 EP1171091 A1 EP 1171091A1
Authority
EP
European Patent Office
Prior art keywords
skin
estrogen
composition according
matrix
pharmaceutical
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.)
Withdrawn
Application number
EP00926811A
Other languages
German (de)
English (en)
Inventor
Holger Zimmermann
Sabine Fricke
Christoph Völkel
Walter Elger
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.)
Dittgen Michael
Jenapharm GmbH and Co KG
Original Assignee
Dittgen Michael
Jenapharm GmbH and Co KG
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
Priority claimed from DE1999118644 external-priority patent/DE19918644A1/de
Application filed by Dittgen Michael, Jenapharm GmbH and Co KG filed Critical Dittgen Michael
Publication of EP1171091A1 publication Critical patent/EP1171091A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation

Definitions

  • the invention relates to pharmaceutical or cosmetic compositions for local intradermal application of estrogens
  • Est ⁇ ol is considered to be a weakly effective estrogen, i.e. the systemic activity is significantly less than that of the other estrogens.
  • Punnonen et al Punnonen R, Vaajalahti P, Teisala K, Ann Chir Gynaecol Suppl 1987, 202, 39 - 41 found that after local application, Est ⁇ ol maintains the elasticity of the skin.
  • Transdermal therapeutic systems are suitable for demanding the active ingredient through the skin in particular, possibly with the aid of penetration and / or permeation promoters. These often cause temporary damage to the upper layers of the skin, which makes their use problematic
  • DE 196 35 883 A1 describes a transdermal therapeutic system of a combination of Est ⁇ ol with one or more further active ingredients, preferably those which take advantage of the supportive effect of Est ⁇ ol in the treatment of osteoporosis, arterosclerosis and heart failure, for example beta blockers and Ca antagonists
  • WO 95/22322 describes a transdermal therapeutic system for the application of sex steroids which, in the case of Est ⁇ ol, contains penetration enhancers and installation inhibitors.
  • WO 93/18774 describes the use of Est ⁇ ol for the production of a transdermal drug continuously releasing the active ingredient for the treatment of climactic osteoporosis.
  • a pharmaceutical formulation is disclosed which ensures the complete systemic availability of Est ⁇ ol
  • EP 0 765 663 A2 describes the use of dienogest or a combination of dienogest and an estrogen for the treatment of acne vulga ⁇ s seborrhea alopecia and androgen symptoms of women with a pharmaceutical preparation which makes the active ingredient available locally and prevents systemic side effects.
  • the object of this invention is, however To provide dienogest locally, the estrogen, if necessary, only to be added as a supporting agent
  • the object is achieved in that a pharmaceutical or cosmetic composition for local, intradermal application of estrogens containing at least one estrogen in combination with a structuring agent is created in a common matrix
  • estrogen refers to steroidal or non-steroidal substances which stimulate the growth of the genital organs, which develop female sexual characteristics and which can more or less proliferate a resting endometnum, in particular human estrogens such as estrone, estradiol, estratnol, equine Estrogens such as Equihn 17 -estrad ⁇ ol, phytoestrogens such as rhaponticin, understood It is particularly advantageous if the estrogen is a synthetic or biogenic estrogen or a compound which closes off one of the abovementioned compounds rapidly after application, for example esterified estrogen such as estradiol valerate or benzoate, estrogen sulfamate conjugated estrogen such as estrone sulfate or estolol glucuride or a mixture of natural and / or synthetic estrogens , such as an extract from certain palm kernels
  • the estrogen is est ⁇ ol or ⁇ - or ⁇ -estradiol or is a compound which rapidly cleaves one of the abovementioned compounds after application
  • composition according to the invention is further characterized in that the structuring agent is selected, for example, from sucrose lactose mannitol, mannitose, succinic acid or a mixture of the aforementioned substances
  • the matrix is a molecularly disperse distribution of the estrogen in a structuring agent, the structuring agent being selected, for example, from sucrose, lactose, mannitol, mannitose succinic acid or a mixture of the aforementioned substances
  • the molecularly disperse distribution additionally contains an auxiliary which is selected, for example, from polyethylene glycols, polyvinylpyrrolidones, cellulose derivatives or mixtures thereof
  • the matrix is suspended or emulsified in a base suitable for intradermal use, such as creams, ointments, emulsions, suspensions, gels or other semi-solid systems
  • Another object of the present invention is the use of the composition according to the invention for the manufacture of a medicament, for example creams, ointments, emulsion suspensions, gels or other semi-solid systems, for the treatment of skin aging and for the reduction of wrinkles in the skin So the most important thing is. to keep the systemic effects of the hormones (estrogens) as low as possible. In this case, the systemic availability is an effect which is undesirable for local application in the skin.
  • a medicament for example creams, ointments, emulsion suspensions, gels or other semi-solid systems
  • composition according to the invention effects the permeation of estrogens through the skin, but there is no high systemic availability and action.
  • the present invention thus excellently achieves the object of providing a pharmaceutical or cosmetic preparation which allows hormones, preferably estriol, ⁇ - and ⁇ -estradiol, to penetrate the skin to a sufficient extent (penetration) and at the same time the hormone in the upper layers of skin fixed as a depot so that the hormones do not penetrate the skin completely (permeation).
  • hormones preferably estriol, ⁇ - and ⁇ -estradiol
  • the basic idea of the invention is that the preparation according to the invention enriches water in the upper layers of the skin, which serves as a depot for the hormones. This seems to enable local effectiveness, but at the same time renders penetration of the skin and thus a systemic effect impossible.
  • FIG. 1 shows that the preparation according to the invention stores more water in the upper layers of the skin, which results in a hormone depot.
  • the light areas of the fingertip (R) shown show a significantly increased signal intensity of the proton spin densities in the skin areas, which were treated with the cream, which contains structuring agents.
  • the dark areas (L) show a comparison preparation without a structuring agent, in which water is not stored and the hormone is not stored.
  • hormones preferably estrogens such as estriol or estradiol
  • a structure-forming agent of the water structure preferably a solid dispersion, a sprayed premix (premix) or a mixture of both forms.
  • the invention is illustrated by the following examples.
  • a matrix of the following composition is produced by spray drying:
  • estriol is partially amorphized compared to the starting substance and has a particle size smaller than 8 ⁇ m (50%).
  • a matrix of the following composition is produced by spray drying: Estradiol 3 parts by mass
  • estriol is amorphized compared to the starting substance and has a particle size of less than 8 ⁇ m (50%).
  • FIG. 2 shows the pharmacokinetics of estriol from a preparation according to the invention according to Example 1.
  • Example 5 The blood levels shown in FIG. 2 clearly show that the systemically available free estriol after using a preparation according to the invention according to Example 1 is in the subtherapeutic range of only up to 10 pg / ml. The permeation is therefore very weak.
  • Example 5 The blood levels shown in FIG. 2 clearly show that the systemically available free estriol after using a preparation according to the invention according to Example 1 is in the subtherapeutic range of only up to 10 pg / ml. The permeation is therefore very weak.
  • Example 2 A pharmaceutical or cosmetic preparation according to Example 1, which contained 1% estriol, was applied to the excised udder udder skin (thickness: approx. 1.0 mm, area: 1, 77 cm 2 ). The transdermal permeation was determined by means of the total permeated mass of estriol in 48 hours and the penetration by means of the content of estriol in the treated skin area. The results are shown in FIG. 3.
  • Figure 3 is a representation of the permeated and penetrated mass of estriol.
  • the mass of estriol that has penetrated the skin is 50 times higher after 48 hours than that which has permeated through the skin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Birds (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Préparations pharmaceutiques ou cosmétiques pour l'application locale intradermique d'oestrogènes, qui contiennent au moins un oestrogène en combinaison avec une substance de formation de structure dans une matrice commune. Des systèmes de ce type sous forme de crèmes, d'onguents, d'émulsions, de suspensions, de gels ou d'autres systèmes à demi-solides garantissent un séjour à long terme et à haute concentration des hormones dans la peau et empêchent les hormones de se disperser de manière systémique. Lesdites préparations servent à traiter le vieillissement de la peau et à réduire les rides.
EP00926811A 1999-04-16 2000-04-05 Preparations pharmaceutiques ou cosmetiques pour l'application locale intradermique d'hormones Withdrawn EP1171091A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE1999118644 DE19918644A1 (de) 1999-04-16 1999-04-16 Pharmazeutische Zusammensetzungen zur lokalen, intradermalen Applikation von Estrogenen
DE19918644 1999-04-16
US13062499P 1999-04-26 1999-04-26
US130624P 1999-04-26
PCT/EP2000/002999 WO2000062753A1 (fr) 1999-04-16 2000-04-05 Preparations pharmaceutiques ou cosmetiques pour l'application locale intradermique d'hormones

Publications (1)

Publication Number Publication Date
EP1171091A1 true EP1171091A1 (fr) 2002-01-16

Family

ID=26053065

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00926811A Withdrawn EP1171091A1 (fr) 1999-04-16 2000-04-05 Preparations pharmaceutiques ou cosmetiques pour l'application locale intradermique d'hormones

Country Status (4)

Country Link
EP (1) EP1171091A1 (fr)
JP (1) JP2003527310A (fr)
AU (1) AU4543200A (fr)
WO (1) WO2000062753A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8048869B2 (en) 2001-05-18 2011-11-01 Pantarhei Bioscience B.V. Pharmaceutical composition for use in hormone replacement therapy
EP1390042B1 (fr) 2001-05-23 2007-11-28 Pantarhei Bioscience B.V. Systeme d'administration de medicament comprenant un oestrogene tetrahydroxyle destine a une contraception hormonale
CA2448273C (fr) 2001-05-23 2010-06-29 Christian Franz Holinka Systeme d'administration de medicament a base d'oestrogenes tetrahydroxyles pour la contraception hormonale
DK1446128T3 (da) 2001-11-15 2007-04-02 Pantarhei Bioscience Bv Anvendelse af östrogenforbindelser i kombination med progestogenforbindelser i hormonsubstitutionsbehandling
PT1511496E (pt) 2002-06-11 2007-01-31 Pantarhei Bioscience Bv Método para tratamento ou prevenção de doenças mediadas pelo sistema imunitário e formulação farmacológica para utilização nas mesmas
US7943604B2 (en) 2002-06-11 2011-05-17 Pantarhei Bioscience B.V. Method of treating human skin and a skin care composition for use in such a method
DK1526856T3 (da) 2002-07-12 2008-03-10 Pantarhei Bioscience Bv Farmaceutisk sammensætning omfattende estetrolderivater til anvendelse i cancerterapi
EP2114412B1 (fr) 2007-01-08 2010-07-14 Pantarhei Bioscience B.V. Procédé pour traiter ou empêcher l'infertilité chez un mammifère femelle et un kit pharmaceutique à utiliser dans un tel procédé

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DE2350315C2 (de) * 1973-10-06 1984-01-12 Johnson & Johnson GmbH, 4000 Düsseldorf Pharmazeutische und kosmetische Präparate zur äußerlichen Anwendung
ATE95430T1 (de) * 1984-12-22 1993-10-15 Sanol Arznei Schwarz Gmbh Wirkstoffpflaster.
CN1021196C (zh) * 1986-12-29 1993-06-16 新泽西州州立大学(鲁杰斯) 透皮***/孕激素药剂单元、***及方法
WO1991006289A1 (fr) * 1989-10-31 1991-05-16 Watson Laboratories, Inc. Support muco-adhesif servant a liberer un agent therapeutique
JP2957694B2 (ja) * 1990-11-30 1999-10-06 株式会社資生堂 皮膚外用剤組成物
DE4400770C1 (de) * 1994-01-13 1995-02-02 Lohmann Therapie Syst Lts Wirkstoffhaltiges Pflaster zur Abgabe von Estradiol mit mindestens einem Penetrationsverstärker, Verfahren zu seiner Herstellung und seine Verwendung
DE4416927C1 (de) * 1994-05-13 1995-08-31 Lohmann Therapie Syst Lts Vorrichtung zur Abgabe von Wirkstoffen aus Haftschmelzklebern, Verfahren zu ihrer Herstellung und ihre Verwendung
FR2732223B1 (fr) * 1995-03-30 1997-06-13 Sanofi Sa Composition pharmaceutique pour administration transdermique
DE19534209A1 (de) * 1995-09-15 1997-03-20 Jenapharm Gmbh Hormonales Mittel zur Behandlung der Haut
DE19634206C2 (de) * 1996-08-26 2000-01-20 Ludwig Reinke Hautpflegemittel, insbesondere für alternde Haut
DE19652196A1 (de) * 1996-12-16 1998-06-18 Jenapharm Gmbh Homogene steroidhaltige Präformulierungen zur Herstellung niedrigdosierter fester und halbfester pharmazeutischer Zubereitungen
DE19701949A1 (de) * 1997-01-13 1998-07-16 Jenapharm Gmbh Transdermales therapeutisches System
ATE287257T1 (de) * 1997-01-16 2005-02-15 Massachusetts Inst Technology Zubereitung von partikelhaltigen arzneimitteln zur inhalation
US6030620A (en) * 1997-07-25 2000-02-29 Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. Skin care compositions containing an organic extract of chick pea

Non-Patent Citations (1)

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Title
See references of WO0062753A1 *

Also Published As

Publication number Publication date
JP2003527310A (ja) 2003-09-16
AU4543200A (en) 2000-11-02
WO2000062753A1 (fr) 2000-10-26

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