SK25299A3 - Transdermal therapeutical approach involving a combination of active substances containing oestriol - Google Patents
Transdermal therapeutical approach involving a combination of active substances containing oestriol Download PDFInfo
- Publication number
- SK25299A3 SK25299A3 SK252-99A SK25299A SK25299A3 SK 25299 A3 SK25299 A3 SK 25299A3 SK 25299 A SK25299 A SK 25299A SK 25299 A3 SK25299 A3 SK 25299A3
- Authority
- SK
- Slovakia
- Prior art keywords
- estriol
- combination
- transdermal therapeutic
- oestriol
- therapeutic system
- Prior art date
Links
Classifications
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Vynález sa týka transdermálneho terapeutického systému s estriolom, ktorý obsahuje kombináciu aktívnych prísad.The invention relates to a transdermal therapeutic system with estriol comprising a combination of active ingredients.
Estrogény sú steroidné hormóny, ktoré sa odvodzujú z tetracyklického Cis steroidu estránu. Medzi prírodnými estrogénmi sa rozlišujú estróny, estradioly a estrioly, pričom eštrón a estriol sú z fyziologického hľadiska najdôležitejšie.Estrogens are steroid hormones that are derived from the tetracyclic Cis steroid estran. Estrogen, estradiol and estriol are distinguished between natural estrogens, with estrone and estriol being most important physiologically.
Estriol je jeden z konečných metabolických produktov estradiólnej látkovej výmeny. Má rad farmakologických a biologických zvláštností, ktoré sa od ostatných estrogénov líšia.Estriol is one of the final metabolic products of estradiol metabolism. It has a number of pharmacological and biological peculiarities that differ from other estrogens.
Už pred adsorpciou sa takmer celkom spája. Len 1 - 2 % používaného estriolu sa v krvnom obehu prejavuje ako voľný estriol. Podiel voľného estriolu k spojovateľnému je 1:500.Already before adsorption, it is almost completely bonded. Only 1 - 2% of estriol used is in the bloodstream as free estriol. The ratio of free estriol to connectable is 1: 500.
Pri ústnej dávke 2 mg sa neprejaví žiaden proliferačný účinok na endometriu, pretože tu zostáva veľmi krátko spojený s receptormi jadra bunky. Estrogénny účinok sa prejavuje len vtedy, ak estrogénna substancia ostane dlhšiu dobu v jadre. To je možné dosiahnúť, pokiaľ sa estriol podáva niekoľkokrát denne.At an oral dose of 2 mg, no proliferative effect on the endometrium appears, since it remains very briefly associated with the cell nucleus receptors. The estrogenic effect is only manifested if the estrogenic substance remains in the nucleus for a long time. This can be achieved when estriol is administered several times a day.
Ďalšou zvláštnosťou estriolu je, že pokiaľ sa podáva po dobu niekoľkých mesiacov, nadobúda na účinnosti.Another peculiarity of estriol is that it is effective when administered for several months.
j Vaginálna aplikácia má tú výhodu, že nespojiteľnosť estriolu do séra je 10 až 20x vyššia, ako pri ústnej dávke, pri ktorej je možný intestinálny metabolizmus. Po dávkeThe vaginal application has the advantage that the estriol non-connectivity to serum is 10 to 20 times higher than at an oral dose at which intestinal metabolism is possible. After dose
I ' • 0,5 mg estriolu pri vaginálnej aplikácii sa môže už po dvoch hodinách počítať s vysokou hladinou séra od 100 - 150 pg/m1. Oproti tomu, aby sa dosiahol rovnaký účinok, je potrebné pri ústnej dávke 10 mg.0.5 mg of estriol for vaginal administration can be expected to have a high serum level of 100-150 pg / ml after only two hours. In contrast, an oral dose of 10 mg is required to achieve the same effect.
Predtým spomenutými poznatkami sa dochádza k záveru, že estriol predstavuje transdermálny terapeutický systém (TTS), galenický systém voľby. Týmto systémom sa môže zaistiť, aby sa estriol po určitú dobu, napr. sedem dní, nepretržite prenášal na organizmus.The foregoing findings conclude that estriol is a transdermal therapeutic system (TTS), a galenical system of choice. These systems can ensure that estriol is used for a certain period of time, e.g. seven days, continuously transmitted to the body.
-2Účinnej látke estriolu sa dosiaľ prisudzovalo nedostatočné terapeutické pôsobenie v rámci substitučnej terapie (HRT). Toto platí najmä pri použití estriolu ako prevencie osteoporózy. V oficiálnom stanovisku Nemeckej spoločnosti endokrinológie sa zdôrazňuje neúčinnosť estriolu ako profylaxie osteoporózy (porovnaj: Nemecké lekárske noviny - Lekárske správy, 85, 1322 -1325, 1988).To date, the active substance estriol has been attributed to a lack of therapeutic action in substitution therapy (HRT). This is particularly true when estriol is used to prevent osteoporosis. The official opinion of the German Society of Endocrinology emphasizes the ineffectiveness of estriol as a prophylaxis for osteoporosis (cf. German Medical Newspaper - Medical Reports, 85, 1322-1325, 1988).
To, že estriol nepôsobí na kosti, bolo publikované aj v príslušných lekárskych knihách (Freimut A. Leidenberger, Klinická endokrinológia pre ženských lekárov, Springerovo nakladateľstvo 1992, str. 356).The fact that estriol does not act on bones has also been published in relevant medical books (Freimut A. Leidenberger, Clinical Endocrinology for Female Doctors, Springer Publishing House 1992, p. 356).
Na neúčinnosť samotného estriolu pri liečení osteoporózy sa poukazuje aj vo Výrobných informáciách na preparáty, ktoré zahŕňajú estriol ako aktívnu prísadu (napr. Jenapharm liečiva: Sortiment a cenz z 1. 7. 1991, str. 67).The ineffectiveness of estriol alone in the treatment of osteoporosis is also pointed out in the Product Information Sheet for preparations that include estriol as an active ingredient (eg Jenapharm Drugs: Assortment and Census, July 1, 1991, p. 67).
Oproti tomu sa estriol predstavuje v PCT-prihláške WO 93/18774 ako jediný na použitie pri liečení osteoporózy formou transdermálneho terapeutického systému. Podľa posudkov je estriol z estragónov vhodný na nepretržitú hormonálnu substitučnú terapiu a najmä na terapiu klimakterickej osteoporózy. Pri nepretržitom podávaní sa totiž na jednej strane dosahuje účinná terapia, prípadne prevencia, zatiaľ čo na druhej strane odpadá obvykle zrejmý estrogénny karcerogénny účinok a dokonca sa môže očakávať antikarcerogénny účinok.In contrast, estriol is the only one for use in the treatment of osteoporosis in the form of a transdermal therapeutic system in PCT application WO 93/18774. Estragol from tarragons is found to be suitable for continuous hormone replacement therapy and in particular for the treatment of climacteric osteoporosis. Indeed, on continuous administration, effective therapy or prevention is achieved on the one hand, while on the other hand, there is usually no obvious estrogenic carcerogenic effect and even anticarcerogenic effect can even be expected.
Podstata vynálezuSUMMARY OF THE INVENTION
Ak vychádzame z tohto stavu medicíny základná úloha vynálezu spočíva v tom, aby sa uviedol podstatne zlepšený transdermálny terapeutický systém s estriolom, ktorý obsahuje kombinácie aktívnych prísad a ktorý má bez rizika a vedľajších účinkov, najmä počas 1 ' i i použitia estriolu, vysokú terapeutickú účinnosť a akceptáciu na prevenciu osteoporózy, artériosklerózy a/alebo srdcovej insuficiencie v starobe.Starting from the present state of medical primary object of the invention consists in that said substantially improved transdermal therapeutic system of estriol containing a combination of active ingredients, and having no risk of side effects, in particular for 1 'ii using estriol, a high therapeutic activity and acceptance to prevent osteoporosis, arteriosclerosis, and / or cardiac insufficiency in old age.
S prekvapením sa zistilo, že účinok transdermálne aplikovaného estriolu podporujú transdermálne aplikované bifosfonáty, bet-ablokátory a Ca-antagonisty a že transdermálne aplikovaný estriol v kombinácii s beta-blokátormi a Ca-antagonistami sa používa pri liečbe artériosklerózy, poprípade pri liečbe srdcovej insuficiencie v starobe. V kombinácii s bifosfonátmi je vhodný aj na transdermálnu aplikáciu pri liečbe osteoporózy.Surprisingly, it has been found that transdermally administered estriol is supported by transdermally administered bisphosphonates, beta-ablocators and Ca-antagonists and that transdermally applied estriol in combination with beta-blockers and Ca-antagonists is used in the treatment of arteriosclerosis or in the treatment of heart failure . In combination with bisphosphonates, it is also suitable for transdermal application in the treatment of osteoporosis.
-3Pri ďalších použitiach sa zistilo, že pri liečbe osteoporózy je výhodnejšia dransdermálna aplikácia bifosfonátov v kombinácii s estriolom, ako samotný estriol. Uprednostňuje sa taká forma dávky, ktorá počas 24 hodín uvoľňuje 8 až 16 mg estriolu a 3 až 7 mg bifosfonátov na TTS.In other uses, it has been found that dransdermal administration of bisphosphonates in combination with estriol is preferable to estriol alone in the treatment of osteoporosis. A dosage form is preferred which releases 8 to 16 mg of estriol and 3 to 7 mg of bisphosphonates per TTS over 24 hours.
Na tento účel sú podľa vynálezu určené všetky transdermálne terapeutické systémy s estriolom, obsahujúce kombinácie aktívnych prísad, ktoré zaručujú nepretržité uvoľňovanie aktívnych prísad počas najmenej 24 hodinách. Výroba takéhoto systému so zodpovedajúcimi jednotlivými substanciami je odborníkovi známa a je aj príslušne popísaná.For this purpose, all transdermal therapeutic systems with estriol containing combinations of active ingredients which guarantee the continuous release of active ingredients for at least 24 hours are intended according to the invention. The preparation of such a system with corresponding individual substances is known to the person skilled in the art and is also described accordingly.
Claims (5)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19635883A DE19635883A1 (en) | 1996-09-04 | 1996-09-04 | Transdermal therapeutic system with an active ingredient combination containing estriol |
PCT/EP1997/004392 WO1998009631A1 (en) | 1996-09-04 | 1997-08-13 | Transdermal therapeutical approach involving a combination of active substances containing oestriol |
Publications (1)
Publication Number | Publication Date |
---|---|
SK25299A3 true SK25299A3 (en) | 2000-08-14 |
Family
ID=7804611
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK252-99A SK25299A3 (en) | 1996-09-04 | 1997-08-13 | Transdermal therapeutical approach involving a combination of active substances containing oestriol |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0927036B9 (en) |
JP (1) | JP2000517324A (en) |
KR (1) | KR20010029451A (en) |
CN (1) | CN1228702A (en) |
AT (1) | ATE289818T1 (en) |
AU (1) | AU729898B2 (en) |
CA (1) | CA2261655A1 (en) |
CZ (1) | CZ70099A3 (en) |
DE (2) | DE19635883A1 (en) |
ES (1) | ES2239362T3 (en) |
IL (1) | IL128768A0 (en) |
NO (1) | NO991047L (en) |
NZ (1) | NZ334443A (en) |
PL (1) | PL332035A1 (en) |
SK (1) | SK25299A3 (en) |
WO (1) | WO1998009631A1 (en) |
ZA (1) | ZA977895B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100266670A1 (en) | 2007-12-10 | 2010-10-21 | Akira Yamamoto | Transdermally absorptive preparation |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5656286A (en) * | 1988-03-04 | 1997-08-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
US5474783A (en) * | 1988-03-04 | 1995-12-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
HU215124B (en) * | 1991-02-26 | 1998-09-28 | Norwich Eaton Pharmaceuticals, Inc. | Process for producing synergetic pharmaceutical compositions containing estrogen and diphosphonate for treating osteoporosis |
CA2131822C (en) * | 1992-03-21 | 2002-12-17 | Walter Elger | Use of estriol for treating climacteric osteoporosis |
JPH0679002A (en) * | 1993-12-14 | 1994-03-22 | Hisamitsu Pharmaceut Co Inc | Patch device for percutaneous administration |
DE4405898A1 (en) * | 1994-02-18 | 1995-08-24 | Schering Ag | Transdermal therapeutic systems containing sex steroids |
-
1996
- 1996-09-04 DE DE19635883A patent/DE19635883A1/en not_active Withdrawn
-
1997
- 1997-08-13 WO PCT/EP1997/004392 patent/WO1998009631A1/en not_active Application Discontinuation
- 1997-08-13 CZ CZ99700A patent/CZ70099A3/en unknown
- 1997-08-13 EP EP97937573A patent/EP0927036B9/en not_active Expired - Lifetime
- 1997-08-13 JP JP10512160A patent/JP2000517324A/en active Pending
- 1997-08-13 PL PL97332035A patent/PL332035A1/en unknown
- 1997-08-13 AU AU40150/97A patent/AU729898B2/en not_active Ceased
- 1997-08-13 SK SK252-99A patent/SK25299A3/en unknown
- 1997-08-13 ES ES97937573T patent/ES2239362T3/en not_active Expired - Lifetime
- 1997-08-13 DE DE59712215T patent/DE59712215D1/en not_active Expired - Lifetime
- 1997-08-13 IL IL12876897A patent/IL128768A0/en unknown
- 1997-08-13 CA CA002261655A patent/CA2261655A1/en not_active Abandoned
- 1997-08-13 NZ NZ334443A patent/NZ334443A/en unknown
- 1997-08-13 AT AT97937573T patent/ATE289818T1/en not_active IP Right Cessation
- 1997-08-13 CN CN97197615A patent/CN1228702A/en active Pending
- 1997-08-13 KR KR1019997001714A patent/KR20010029451A/en not_active Application Discontinuation
- 1997-09-03 ZA ZA9707895A patent/ZA977895B/en unknown
-
1999
- 1999-03-03 NO NO991047A patent/NO991047L/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
ATE289818T1 (en) | 2005-03-15 |
EP0927036A1 (en) | 1999-07-07 |
ZA977895B (en) | 1998-03-02 |
AU729898B2 (en) | 2001-02-15 |
JP2000517324A (en) | 2000-12-26 |
KR20010029451A (en) | 2001-04-06 |
DE19635883A1 (en) | 1998-03-05 |
ES2239362T3 (en) | 2005-09-16 |
EP0927036B1 (en) | 2005-03-02 |
NO991047D0 (en) | 1999-03-03 |
AU4015097A (en) | 1998-03-26 |
CZ70099A3 (en) | 1999-07-14 |
CA2261655A1 (en) | 1998-03-12 |
NO991047L (en) | 1999-03-03 |
CN1228702A (en) | 1999-09-15 |
PL332035A1 (en) | 1999-08-16 |
EP0927036B9 (en) | 2005-08-10 |
IL128768A0 (en) | 2000-01-31 |
NZ334443A (en) | 1999-08-30 |
WO1998009631A1 (en) | 1998-03-12 |
DE59712215D1 (en) | 2005-04-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2139056C1 (en) | Hormonal substitutional therapy | |
US5422119A (en) | Transdermal hormone replacement therapy | |
JP5184727B2 (en) | Parenteral androgenic steroid administration to women | |
AU711179B2 (en) | Cyclophasic hormonal regimen containing antiprogestin and progestin | |
RU2340345C2 (en) | Scheme of estrogen replenishment | |
JP3314207B2 (en) | Hormone preparations and methods | |
TWI362932B (en) | Pharmaceutical composition for transdermal delivery and uses thereof | |
JPH03502932A (en) | Contraceptive systems and methods | |
US5286490A (en) | Transdermal fluoride medication | |
SK25299A3 (en) | Transdermal therapeutical approach involving a combination of active substances containing oestriol | |
AU692155B2 (en) | Method and composition for treatment of osteoporosis | |
MXPA99001793A (en) | Transdermal therapeutical approach involving a combination of active substances containing oestriol | |
CA2171460C (en) | Preparation for substitution therapy, containing at least one progestogen and at least one extrogen | |
MACMASTER et al. | Treatment of severe weight loss with methandrostenolone—a less virilizing anabolic agent | |
EP0675720A1 (en) | Transdermal, multiphasic hormone replacement therapy | |
Mishell Jr | The transdermal contraceptive system: Efficacy and safety | |
AU3662300A (en) | Use of sex hormones to obtain a nasal pharmaceutical composition that is useful in the treatment of undesirable uterine bleeding | |
MXPA01008772A (en) | Use of sex hormones to obtain a nasal pharmaceutical composition that is useful in the treatment of undesirable uterine bleeding |