EP1023053A1 - Systeme therapeutique transdermique contenant de l'acide acetylsalicylique a resorption renforcee - Google Patents

Systeme therapeutique transdermique contenant de l'acide acetylsalicylique a resorption renforcee

Info

Publication number
EP1023053A1
EP1023053A1 EP98902976A EP98902976A EP1023053A1 EP 1023053 A1 EP1023053 A1 EP 1023053A1 EP 98902976 A EP98902976 A EP 98902976A EP 98902976 A EP98902976 A EP 98902976A EP 1023053 A1 EP1023053 A1 EP 1023053A1
Authority
EP
European Patent Office
Prior art keywords
limonene
acetylsalicylic acid
therapeutic system
dimethyl isosorbide
transdermal therapeutic
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Withdrawn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
EP98902976A
Other languages
German (de)
English (en)
Inventor
Michael Horstmann
Gerd Hoffmann
Heinrich Kindel
Theresa Maria Murphy
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 EP1023053A1 publication Critical patent/EP1023053A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • 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
    • A61K9/7092—Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs

Definitions

  • the invention relates to a transdermal therapeutic system containing acetylsalicylic acid with an essentially active substance and moisture impermeable back layer, an active substance reservoir and optionally a removable protective layer.
  • TTS Transdermal therapeutic systems
  • Acetylsalicylic acid is a relatively safe drug with a high therapeutic index. It is used as an anti-inflammatory drug in very high doses (over one gram per day), as an antipyretic / analgesic in medium doses (250-500 mg) and as a platelet aggregation inhibitor in low doses (30 to 150 mg per day). Acetylsalicylic acid is a substance that melts at a low temperature (approx. 139 ° C) and is already noticeably volatile at this temperature.
  • Acetylsalicylic acid is susceptible to hydrolysis and transesterification due to the unstable ester grouping.
  • stabilization methods have already been considered, such as elimination of water, alcohols and esters as possible reaction partners for a transesterification or saponification; Add acetic acid or acetic anhydride or adjust pH 2-3.
  • dimethyl isosorbide is also mentioned as a stabilizing solvent.
  • a major obstacle to the development of pharmaceutically active transdermal therapeutic systems containing acetylsalicylic acid is, moreover, the low permeability of the active substance through the skin compared to the high required daily therapeutic dose.
  • Numerous permeation accelerators have therefore already been proposed as additives, such as azones, carboxylic acid esters and surface-active substances Etc.
  • US Pat. No. 5,164,416 also specifies limonene as a permeation-enhancing substance for acetylsalicylic acid, but its use is then restricted to the simultaneous addition of a possibly irritating alkaline additive. Furthermore, the permeation rates achievable for acetylsalicylic acid - following this teaching - are not yet sufficiently high.
  • the transdermal therapeutic system of the type mentioned at the outset is essentially characterized by a content of limonene and Dimethyl isosorbide in a mixing ratio of at least 50:50 (g / g) limonene to dimethyl isosorbide in the active substance range.
  • the principle according to the invention can be used both in matrix systems and in reservoir / membrane systems. It is also irrelevant which polymers, resins and possibly other additives are added, provided the formulation is only suitable for delivering the basic substances acetylsalicylic acid, limonene and dimethylisosorbide to the skin.
  • all three characteristic feedstocks can be dispersed or dissolved in a solution of base polymers, the mixture can be coated on a suitable base, usually a siliconized thermoplastic film, and, after evaporation of the solvent components, possibly reinforced by the addition of heat , are covered with another film, which makes up the back of the transdermal therapeutic system.
  • a suitable base usually a siliconized thermoplastic film
  • another film which makes up the back of the transdermal therapeutic system.
  • a two-layer matrix is formed from a skin-side layer which contains the active ingredient in dispersed or dissolved form and a second skin-facing layer which contains limonene and dimethyl isosorbide in the desired mixing ratio.
  • these design variants are only the simplest of a number of possible system designs known to the person skilled in the art. Of course, matrix systems with more than two layers are possible and additional active ingredients can be provided if necessary.
  • Suitable base polymers for the system according to the invention are in particular acrylate copolymers, styrene / diene copolymers, silicone polymers, mixtures of polyisobutylene with suitable thermoplastic resins. This list is far from complete, but does show the broad applicability of the principle according to the invention.
  • the mixing ratio of limonene to dimethyl isosorbide is in particular in the range from 50:50 to 99: 1, preferably in the range from 85:15 to 95: 5 and especially in the range from 90:10.
  • a limonene fraction which is of the order of magnitude of the acetylsalicyl acid concentration can expediently be provided.
  • the mass is coated on a siliconized polyester film (100 ⁇ m thick) so that a layer of 150 g per m 2 basis weight is formed. Drying is gently achieved by storing in air for 10 hours at room temperature. A further film (polyester film 15 ⁇ m thick) is applied to this matrix by lamination and circular die-cuts of 20 cm 2 in size are produced with punch iron.
  • transdermal therapeutic systems were obtained which, after the siliconized polyester film had been detached, could be applied directly to the skin in order to produce the desired therapeutic effect.
  • a 2.54 cm 2 round fleece disc (cotton) is applied to the adhesive area of the laminate from (2). 8.5 mg of a mixture of 10% (g / g) dimethyl isosorbide and 90% (g / g) limonene, which had been saturated beforehand by stirring for 5 hours at room temperature and then filtering off with acetylsalicylic acid, are dripped onto the fleece disc.
  • Laminate of (1) and fleece disc are covered on the adhesive side with layer (2) so that a sandwich made of polyester film (15 ⁇ m), 52 g / m 2 polyacrylate with acetylsalicylic acid, doped fleece disc 2.54 cm 2 and 93 g / m 2 Polyacrylate with acetylsalicylic acid is formed, which is still covered on the adhesive side by a protective film made of siliconized polyester.
  • Example 3 (comparative example to example 2):
  • Layers 1 and 2 are made according to example 2.
  • a 2.54 cm 2 , round fleece disc (cotton) is applied to the adhesive area of the laminate from (2). 8.5 mg of pure dimethyl isosorbide, which had been saturated beforehand by stirring for 5 hours at room temperature and then filtering with acetylsalicylic acid, are dripped onto the nonwoven disk. Laminate from (1) and fleece disc are punched out in a pattern of 7.10 cm 2 analogously to Example 2. A permeation determination was also carried out on excised rat skin.
  • Example 4 (Comparative example to Example 2)
  • Layers 1 and 2 are made according to example 2.
  • a 2.54 cm 2 round fleece disc (cotton) is applied to the adhesive area of the laminate from (2). 8.5 mg of pure limonene, which had been saturated with acetylsalicylic acid by stirring for 5 hours at room temperature and then filtering off, are dripped onto the nonwoven disk.
  • Laminate from (1) and fleece disc are punched out in a pattern of 7.10 cm 2 analogously to Example 2.
  • a permeation determination was also carried out on excised rat skin. After 48 hours, an average permeation of 253.3 ⁇ g / cm 2 acetylsalicylic acid was found.
  • Example 5 (Comparative example to Example 2)
  • Layers 1 and 2 are made according to example 2.
  • a 2.54 cm 2 round fleece disc (cotton) is applied to the adhesive area of the laminate from (2). No medium is dripped on. Laminate from (1) and fleece disc are punched out in a pattern of 7.10 cm 2 analogously to Example 2. A permeation determination was also carried out on excised rat skin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Ce système thérapeutique transdermique contenant de l'acide acétylsalicylique comprend une couche de fond sensiblement imperméable au principe actif et à l'humidité, un réservoir de principe actif et le cas échéant une couche de protection détachable. Ce système thérapeutique transdermique se caractérise en ce qu'il contient du limonène et de l'isosorbide de diméthyle dans un rapport égal à au moins 50 g de limonène par 50 g d'isosorbide de diméthyle dans la zone du principe actif.
EP98902976A 1997-01-15 1998-01-03 Systeme therapeutique transdermique contenant de l'acide acetylsalicylique a resorption renforcee Withdrawn EP1023053A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19701059 1997-01-15
DE19701059A DE19701059C2 (de) 1997-01-15 1997-01-15 Acetylsalicylsäure enthaltendes transdermales therapeutisches System mit Resorptionsverstärkung
PCT/EP1998/000013 WO1998031348A1 (fr) 1997-01-15 1998-01-03 Systeme therapeutique transdermique contenant de l'acide acetylsalicylique a resorption renforcee

Publications (1)

Publication Number Publication Date
EP1023053A1 true EP1023053A1 (fr) 2000-08-02

Family

ID=7817375

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98902976A Withdrawn EP1023053A1 (fr) 1997-01-15 1998-01-03 Systeme therapeutique transdermique contenant de l'acide acetylsalicylique a resorption renforcee

Country Status (8)

Country Link
EP (1) EP1023053A1 (fr)
JP (1) JP2001508069A (fr)
KR (1) KR20000070228A (fr)
AU (1) AU726094B2 (fr)
CA (1) CA2277366A1 (fr)
DE (1) DE19701059C2 (fr)
NO (1) NO993435L (fr)
WO (1) WO1998031348A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19949252B4 (de) * 1999-10-13 2004-02-12 Lts Lohmann Therapie-Systeme Ag Verwendung eines superfiziellen therapeutischen Systems zur topischen Applikation von Acetylsalicylsäure zur Behandlung von Akne-Erkrankungen und Verfahren zu seiner Herstellung
DE19949202A1 (de) * 1999-10-13 2001-05-03 Lohmann Therapie Syst Lts Transdermales therapeutisches System zur Abgabe von Acetylsalicylsäure und/oder Salicylsäure
DE19959913A1 (de) * 1999-12-11 2001-06-28 Lohmann Therapie Syst Lts Acetylsalicylsäure enthaltendes transdermales System zur Behandlung von Migräne
KR100448469B1 (ko) * 2001-10-26 2004-09-13 신풍제약주식회사 항염증제의 경피 조성물 및 장치
CA2464656C (fr) 2001-11-01 2013-07-16 Nektar Therapeutics Procedes de sechage par atomisation et compositions associees
DE10338162B3 (de) † 2003-08-20 2005-06-02 Haldex Brake Products Gmbh Verfahren zum Betreiben einer Druckluftbeschaffungsanlage eines Kraftfahrzeuges sowie Druckluftaufbereitungseinrichtung
DE102005033543A1 (de) * 2005-07-14 2007-01-18 Grünenthal GmbH Ein einen Duftstoff aufweisendes transdermales therapeutisches System
DE102005050431A1 (de) 2005-10-21 2007-04-26 Lts Lohmann Therapie-Systeme Ag Transdermales therapeutisches System zur Verabreicherung lipophiler und/oder wenig hautpermeabler Wirkstoffe
IT202000014578A1 (it) * 2020-06-18 2021-12-18 Poli Md S R L Dispositivo medicale comprendente acido acetil salicilico

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4228162A (en) * 1979-07-09 1980-10-14 Research Corporation Dimethyl isosorbide in liquid formulation of aspirin
US5164416A (en) * 1989-02-03 1992-11-17 Lintec Corporation Transdermal therapeutic formulation containing a limonene
DE4332093C2 (de) * 1993-09-22 1995-07-13 Lohmann Therapie Syst Lts Transdermales therapeutisches System mit dem Wirkstoff Acetylsalicylsäure und Verfahren zu seiner Herstellung
DE4332094C2 (de) * 1993-09-22 1995-09-07 Lohmann Therapie Syst Lts Lösemittelfrei herstellbares Wirkstoffpflaster und Verfahren zu seiner Herstellung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9831348A1 *

Also Published As

Publication number Publication date
KR20000070228A (ko) 2000-11-25
CA2277366A1 (fr) 1998-07-23
AU5986298A (en) 1998-08-07
NO993435D0 (no) 1999-07-12
WO1998031348A1 (fr) 1998-07-23
JP2001508069A (ja) 2001-06-19
DE19701059C2 (de) 2000-12-21
DE19701059A1 (de) 1998-07-16
AU726094B2 (en) 2000-11-02
NO993435L (no) 1999-07-12

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