WO1997004759A1 - Transdermal patch containing aspirin - Google Patents

Transdermal patch containing aspirin Download PDF

Info

Publication number
WO1997004759A1
WO1997004759A1 PCT/IE1996/000049 IE9600049W WO9704759A1 WO 1997004759 A1 WO1997004759 A1 WO 1997004759A1 IE 9600049 W IE9600049 W IE 9600049W WO 9704759 A1 WO9704759 A1 WO 9704759A1
Authority
WO
WIPO (PCT)
Prior art keywords
adhesive
patch
transdermal patch
aspirin
transdermal
Prior art date
Application number
PCT/IE1996/000049
Other languages
French (fr)
Inventor
William Byrne
Dermot Mccafferty
Original Assignee
Cal International Limited
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 Cal International Limited filed Critical Cal International Limited
Priority to GB9801409A priority Critical patent/GB2319473A/en
Priority to AU67091/96A priority patent/AU6709196A/en
Priority to JP9507419A priority patent/JPH11510157A/en
Priority to EP96927180A priority patent/EP0840600A1/en
Publication of WO1997004759A1 publication Critical patent/WO1997004759A1/en

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
    • A61K31/60—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • 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
    • A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
    • 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

Definitions

  • the invention relates to a transdermal delivery system.
  • Aspirin which has been available for about 100 years, possesses analgesic, anti-inflammatory and antipyretic properties. This compound has also been shown to be effective in cardiovascular disease and this action is dependent upon its effects on platelet function. Aspirin can improve the mortality figures associated with acute myocardial infarction and reduces the risk of this in patients with unstable angina by between 30 and 50%. It is used to prevent re-occurrence in those patients after recovery from myocardial infarction. It is also likely to be of benefit to individuals suffering from stable angina since it reduces the risk of myocardial infarction in apparently healthy, middle-aged men. Aspirin is used to reduce the likelihood of stroke in patients with transient cerebral ischaemic attacks. It also lowers the risk of thromboembolism in patients with atrial fibrillation and following valve replacement.
  • Aspirin reduces platelet aggregation by irreversibly inhibiting fatty acid cyclo-oxygenase, a precursor in the biosynthesis of prostaglandins and thromboxanes. This occurs by acetylation of a serine residue and thus prevents access of arachidonic acid to the active site by steric hindrance.
  • Thromboxane A2 is the main cyclo- oxygenase produce of activated platelets and is proaggregatory and a vasoconstrictor. Therefore, aspirin exerts its antithrombotic action by preventing thromboxane A2 biosynthesis.
  • other non-steroidal anti ⁇ inflammatory drugs also possess this effect they are much less effective because, unlike aspirin, they reversibly inhibit the enzyme.
  • transdermal patch containing aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
  • the invention also provides a transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
  • the invention further provides use of aspirin for preparing a transdermal patch comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
  • the invention provides a method for achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
  • the adhesive is a pressure sensitive adhesive, based, for example, on acrylic acid copolymers.
  • the adhesive is applied to the release liner.
  • the release liner is a fluoro-polymeric-coated polyester.
  • the backing comprises a backing layer attached to the adhesive.
  • the backing layer comprises aluminised polyester.
  • the aluminised polyester is sputter coated onto the adhesive.
  • the patch in another embodiment of the invention includes a penetration enhancer to promote the diffusion of the pharmaceutically active product.
  • the invention also provides a method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive.
  • the invention further provides a transdermal patch whenever produced by the method of the invention.
  • the invention provides a method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch of the invention.
  • the purpose of the present invention is to develop a stable transdermal patch system which will deliver sufficient aspirin to the systemic circulation to reduce platelet aggregation. It is a further purpose of this invention to deliver sufficient aspirin to inhibit thromboxane A2 production associated with the platelets but not prostacyline production occurring within the venous endothelium.
  • Fig. 1 is a diagrammatic cross sectional view of a transdermal patch according to the invention.
  • a transdermal patch comprising a pressure sensitive adhesive layer (b) into which the aspirin is incorporated, a release liner (c) and a backing (a).
  • Aspirin has been incorporated directly into a pressure sensitive adhesive such as, but not limited to, acrylic acid copolymers (b) .
  • This mixture can then be cast, rolled or knife-coated onto a suitable release-liner such as, but not limited to, a siliconised polyester (c) .
  • a backing-layer such as, but not limited to, a sputter- coated aluminised polyester (to prevent drug strike through) can then be attached (a).
  • the release-liner (c) is removed before the drug containing adhesive is presented to the skin.
  • this patch has been designed so that skin acts as the rate-determining membrane to drug diffusion. The advantage of this type of system is that it provides the most efficient delivery of drug through the skin.
  • a further advantage of this invention is that aspirin can be delivered systemically avoiding first-pass metabolism. Furthermore, delivering aspirin transdermally will also prevent adverse side-effects on the gastrointestinal tract.
  • a further aspect to this invention is the use of various penetration enhancers to promote the diffusion of aspirin through the skin to the systemic circulation. This would also reduce the size (area) of patch required to deliver a given amount of aspirin to the systemic circulation.
  • penetration enhancers include, but is not limited to, propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol, and/or limonene.
  • Suitable matrices may be used as a drug reservoir. These include the above mentioned acrylate co ⁇ polymers, polyisobutylenes and silicone-based adhesives. Other excipients present in the formulation may include plasticisers such as diethylphthalate, dibutylphthalate, glycerol.
  • a transdermal delivery system for aspirin was prepared in the following way.
  • a pressure sensitive adhesive solution was prepared in the following way.
  • PSA silicone- based (Silescol) sheeting in a modified Franz cell (Fig. 2).
  • DURO-TAK are a range of adhesives available from National Starch.
  • Silescol is manufactured by Esco Rubber and is available from Bibby Sterilin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

A transdermal patch contains aspirin as a pharmaceutically active product having platelet washing properties. The patch comprises a backing, an adhesive for applying the patch and a liner which is released to apply the patch. The aspirin is incorporated into the adhesive.

Description

TRANSDERMAL PATCH CONTAINING ASPIRIN
The invention relates to a transdermal delivery system.
Aspirin, which has been available for about 100 years, possesses analgesic, anti-inflammatory and antipyretic properties. This compound has also been shown to be effective in cardiovascular disease and this action is dependent upon its effects on platelet function. Aspirin can improve the mortality figures associated with acute myocardial infarction and reduces the risk of this in patients with unstable angina by between 30 and 50%. It is used to prevent re-occurrence in those patients after recovery from myocardial infarction. It is also likely to be of benefit to individuals suffering from stable angina since it reduces the risk of myocardial infarction in apparently healthy, middle-aged men. Aspirin is used to reduce the likelihood of stroke in patients with transient cerebral ischaemic attacks. It also lowers the risk of thromboembolism in patients with atrial fibrillation and following valve replacement.
Aspirin reduces platelet aggregation by irreversibly inhibiting fatty acid cyclo-oxygenase, a precursor in the biosynthesis of prostaglandins and thromboxanes. This occurs by acetylation of a serine residue and thus prevents access of arachidonic acid to the active site by steric hindrance. Thromboxane A2 is the main cyclo- oxygenase produce of activated platelets and is proaggregatory and a vasoconstrictor. Therefore, aspirin exerts its antithrombotic action by preventing thromboxane A2 biosynthesis. Although other non-steroidal anti¬ inflammatory drugs also possess this effect they are much less effective because, unlike aspirin, they reversibly inhibit the enzyme. Although the use of oral aspirin has been used for these conditions, there are a number of disadvantages associated with this treatment. The compound has been associated with various gastrointestinal side effects the most severe of which can be gastric bleeding occurring in about 70% of patients taking oral aspirin. Furthermore, the drug is extensively hydrolysed by first-pass metabolism and possesses a half life of about 15 minutes. Salicylic acid, a metabolite of aspirin, has no anti-platelet activity.
Therefore, the development of a suitable transdermal delivery system for aspirin would avoid the side-effects detailed above and would also prevent first-pass metabolism.
According to the invention, there is provided a transdermal patch containing aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
The invention also provides a transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
The invention further provides use of aspirin for preparing a transdermal patch comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
In another aspect, the invention provides a method for achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
Preferably the adhesive is a pressure sensitive adhesive, based, for example, on acrylic acid copolymers.
In one embodiment of the invention, the adhesive is applied to the release liner. Typically, the release liner is a fluoro-polymeric-coated polyester.
Preferably, the backing comprises a backing layer attached to the adhesive. Typically the backing layer comprises aluminised polyester. In one case the aluminised polyester is sputter coated onto the adhesive.
In another embodiment of the invention the patch includes a penetration enhancer to promote the diffusion of the pharmaceutically active product.
The invention also provides a method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive.
The invention further provides a transdermal patch whenever produced by the method of the invention. In another aspect, the invention provides a method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch of the invention.
The purpose of the present invention is to develop a stable transdermal patch system which will deliver sufficient aspirin to the systemic circulation to reduce platelet aggregation. It is a further purpose of this invention to deliver sufficient aspirin to inhibit thromboxane A2 production associated with the platelets but not prostacyline production occurring within the venous endothelium.
The invention will be more clearly understood from the following description thereof given by way of example only with reference to Fig. 1 which is a diagrammatic cross sectional view of a transdermal patch according to the invention.
Referring to Fig. 1, there is illustrated a transdermal patch according to the invention comprising a pressure sensitive adhesive layer (b) into which the aspirin is incorporated, a release liner (c) and a backing (a).
Aspirin has been incorporated directly into a pressure sensitive adhesive such as, but not limited to, acrylic acid copolymers (b) . This mixture can then be cast, rolled or knife-coated onto a suitable release-liner such as, but not limited to, a siliconised polyester (c) . A backing-layer such as, but not limited to, a sputter- coated aluminised polyester (to prevent drug strike through) can then be attached (a). The release-liner (c) is removed before the drug containing adhesive is presented to the skin. Unusually, this patch has been designed so that skin acts as the rate-determining membrane to drug diffusion. The advantage of this type of system is that it provides the most efficient delivery of drug through the skin. This, in turn, will provide the smallest unit area of skin for drug delivery and hence the smallest patch size. This is an important consideration given the possible daily amounts of drug required by the transdermal route. A further advantage of this invention is that aspirin can be delivered systemically avoiding first-pass metabolism. Furthermore, delivering aspirin transdermally will also prevent adverse side-effects on the gastrointestinal tract.
A further aspect to this invention is the use of various penetration enhancers to promote the diffusion of aspirin through the skin to the systemic circulation. This would also reduce the size (area) of patch required to deliver a given amount of aspirin to the systemic circulation. Examples of such penetration enhancers include, but is not limited to, propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol, and/or limonene.
A variety of suitable matrices may be used as a drug reservoir. These include the above mentioned acrylate co¬ polymers, polyisobutylenes and silicone-based adhesives. Other excipients present in the formulation may include plasticisers such as diethylphthalate, dibutylphthalate, glycerol.
Example 1
A transdermal delivery system for aspirin was prepared in the following way. A pressure sensitive adhesive solution
(PSA) was prepared using Duro-Tak 387-2054 dissolved in ethyl acetate. Aspirin (200 mg) was dissolved in 20 g of PSA and cast onto a siliconised release liner using a 10 x 10 cm template. The film was oven dried after which an aluminium sputter-coated polyester backing layer was attached to the exposed, drug-containing, adhesive film (dry weight 5 g) . Thereafter, 1 cm2 sections were cut from the laminate and examined for drug release using silicone- based (Silescol) sheeting in a modified Franz cell (Fig. 2).
Patches (5 x 5 cm2) were also applied to 5 human volunteers for a 24 hour period. Thereafter, the patches were removed and extracted for remaining aspirin. It can be seen from Fig. 3 that, typically 30 - 40% of the drug had been absorbed from the patches within a 24 hour period.
DURO-TAK are a range of adhesives available from National Starch.
Silescol is manufactured by Esco Rubber and is available from Bibby Sterilin.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.

Claims

1. A transdermal patch containing aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
2. A transdermal patch as claimed claim 1 wherein the adhesive is a pressure sensitive adhesive.
3. A transdermal patch as claimed in claim 2 wherein the adhesive is based on acrylic acid copolymers.
4. A transdermal patch as claimed in any preceding claim wherein the adhesive is applied to the release liner.
5. A transdermal patch as claimed in any preceding claim wherein the release liner is a fluoropolymeric-coated polyester.
6. A transdermal patch as claimed in claim 5 wherein the liner is a siliconised release liner.
7. A transdermal patch as claimed in any preceding claim wherein the backing comprises a backing layer attached to the adhesive.
8. A transdermal patch as claimed in any preceding claim wherein the backing layer comprises aluminised polyester.
9. A transdermal patch as claimed in claim 8 wherein the aluminised polyester is sputter coated onto the adhesive.
10. A transdermal patch as claimed in any preceding claim including a penetration enhancer to promote the diffusion of the pharmaceutically active product.
11. A transdermal patch as claimed in claim 10 wherein the penetration enhancer is selected from one or more of propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol and/or limonene.
12. A transdermal patch substantially as hereinbefore described with reference to the example and drawings.
13. A method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive,
coating the adhesive onto a release liner, and
applying a backing layer.
14. A method for producing a transdermal patch substantially as hereinbefore described with reference to the examples and drawings.
15. A transdermal patch whenever produced by a method as claimed in claim 13 or 14.
16. A method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch as claimed in any of claims 1 to 12 or 15.
17. A method for reducing platelet aggregation in a patient substantially as hereinbefore described with reference to the examples and drawings.
18. A transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
19. Use of aspirin for preparing a transdermal patch comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
20. A method for achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
PCT/IE1996/000049 1995-07-27 1996-07-26 Transdermal patch containing aspirin WO1997004759A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
GB9801409A GB2319473A (en) 1995-07-27 1996-07-26 Transdemal patch containing aspirin
AU67091/96A AU6709196A (en) 1995-07-27 1996-07-26 Transdermal patch containing aspirin
JP9507419A JPH11510157A (en) 1995-07-27 1996-07-26 Aspirin-containing transdermal patch
EP96927180A EP0840600A1 (en) 1995-07-27 1996-07-26 Transdermal patch containing aspirin

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IE950575 1995-07-27
IE950575 1995-07-27
IE960368 1996-05-27
IE960368 1996-05-27

Publications (1)

Publication Number Publication Date
WO1997004759A1 true WO1997004759A1 (en) 1997-02-13

Family

ID=26319840

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IE1996/000049 WO1997004759A1 (en) 1995-07-27 1996-07-26 Transdermal patch containing aspirin

Country Status (6)

Country Link
EP (1) EP0840600A1 (en)
JP (1) JPH11510157A (en)
AU (1) AU6709196A (en)
CA (1) CA2228034A1 (en)
GB (1) GB2319473A (en)
WO (1) WO1997004759A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0803254A1 (en) * 1996-04-25 1997-10-29 LUITPOLD PHARMA GmbH Alcoholic solutions containing acetylsalicylic acid for percutaneous administration, their use in antithrombotic therapy and medicaments
EP0920869A1 (en) * 1997-06-25 1999-06-09 Teikoku Seiyaku Co., Ltd. Stable aspirin-containing preparations for external use
WO2001041771A2 (en) * 1999-12-11 2001-06-14 Lts Lohmann Therapie-Systeme Ag Transdermal system containing acetylsalicylic acid for treatment of migraine
WO2011076401A1 (en) 2009-12-23 2011-06-30 Holger Schankin Substantially water-free pharmaceutical compositions containing acetylsalicylic acid
US10758610B2 (en) 2007-12-03 2020-09-01 Dbv Technologies Allergen desensitization method

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2926466B1 (en) * 2008-01-23 2010-11-12 Dbv Tech METHOD FOR MANUFACTURING PATCHES BY ELECTROSPRAY

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4241128A1 (en) * 1991-12-20 1993-06-24 Lohmann Therapie Syst Lts Transdermal aspirin dosage forms - for antithrombotic therapy or cancer prophylaxis
DE4332093A1 (en) * 1993-09-22 1995-03-23 Lohmann Therapie Syst Lts Transdermal therapeutic system with the active ingredient acetylsalicylic acid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4241128A1 (en) * 1991-12-20 1993-06-24 Lohmann Therapie Syst Lts Transdermal aspirin dosage forms - for antithrombotic therapy or cancer prophylaxis
DE4332093A1 (en) * 1993-09-22 1995-03-23 Lohmann Therapie Syst Lts Transdermal therapeutic system with the active ingredient acetylsalicylic acid

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5900412A (en) * 1996-04-25 1999-05-04 Luitpold Pharma Gmbh Percutaneous/transdermal delivery of ASA and antithrombotic therapies based thereon
EP0803254A1 (en) * 1996-04-25 1997-10-29 LUITPOLD PHARMA GmbH Alcoholic solutions containing acetylsalicylic acid for percutaneous administration, their use in antithrombotic therapy and medicaments
EP1273300A2 (en) * 1997-06-25 2003-01-08 Teikoku Seiyaku Co., Ltd. A stable external preparation containing aspirin
EP0920869A1 (en) * 1997-06-25 1999-06-09 Teikoku Seiyaku Co., Ltd. Stable aspirin-containing preparations for external use
EP0920869A4 (en) * 1997-06-25 2000-01-26 Teikoku Seiyaku Kk Stable aspirin-containing preparations for external use
EP1273300A3 (en) * 1997-06-25 2003-01-29 Teikoku Seiyaku Co., Ltd. A stable external preparation containing aspirin
US6268355B1 (en) 1997-06-25 2001-07-31 Teikoku Seiyaku Co., Ltd. Stable aspirin-containing preparations for external use
WO2001041771A3 (en) * 1999-12-11 2001-12-27 Lohmann Therapie Syst Lts Transdermal system containing acetylsalicylic acid for treatment of migraine
WO2001041771A2 (en) * 1999-12-11 2001-06-14 Lts Lohmann Therapie-Systeme Ag Transdermal system containing acetylsalicylic acid for treatment of migraine
US10758610B2 (en) 2007-12-03 2020-09-01 Dbv Technologies Allergen desensitization method
US11202826B2 (en) 2007-12-03 2021-12-21 Dbv Technologies Allergen desensitization method
US11931411B2 (en) 2007-12-03 2024-03-19 Dbv Technologies Allergen desensitization method
WO2011076401A1 (en) 2009-12-23 2011-06-30 Holger Schankin Substantially water-free pharmaceutical compositions containing acetylsalicylic acid

Also Published As

Publication number Publication date
AU6709196A (en) 1997-02-26
GB2319473A (en) 1998-05-27
JPH11510157A (en) 1999-09-07
CA2228034A1 (en) 1997-02-13
GB9801409D0 (en) 1998-03-18
EP0840600A1 (en) 1998-05-13

Similar Documents

Publication Publication Date Title
RU2450805C2 (en) Transdermal therapeutic system
JP2542026B2 (en) Flat treatment device and its manufacturing method
CA2125662C (en) Transdermally administered system containing acetylsalicylic acid for thrombosis therapy and cancer prophylaxis
US5202125A (en) Method and systems for administering nitroglycerin transdermally at enhanced transdermal fluxes
JP3924008B2 (en) A transdermally applicable drug containing an angiotensin converting enzyme (ACE) inhibitor
JP6391664B2 (en) Transdermal drug delivery system containing rivastigmine
WO2001026705A2 (en) A dual adhesive transdermal drug delivery system
KR920010392B1 (en) Process for preparing pharmaceutical composition for the transdermal systemic administration
JPH0725669B2 (en) Pharmaceutical formulation for transdermal administration
WO1997004759A1 (en) Transdermal patch containing aspirin
US5068103A (en) Salbutamol-containing plaster and method of producing same
JP2003520191A (en) Method for producing pressure-sensitive adhesive matrix patches containing hydrophilic salts of drugs
WO1999062557A1 (en) Composition for the transdermal administration of non-steroidal anti-inflammatory drugs
JPH04217919A (en) Percutaneously eperisone or tolperisone-absorbing preparation
IE960540A1 (en) A formulation
KR100322988B1 (en) Anti-inflammatory analgesic compositions and anti-inflammatory analgesics containing them
WO1997004758A1 (en) Pharmaceutical preparation for percutaneous absorbtion
JP2869167B2 (en) Sustained-release patch preparation
IE960539A1 (en) Pharmaceutical preparation for percutaneous absorbtion
JP3799502B2 (en) Transdermal administration system containing acetylsalicylic acid for antithrombotic treatment and cancer prevention
JP2006169160A (en) Plaster for external use and method for producing the same
EP0944384B1 (en) Transdermal drug delivery system for the treatment of heart diseases
WO1997004757A1 (en) Transdermal nitrate formulation
JPH05294832A (en) Dermal plaster
KR20010010664A (en) Contents for the scabicidal and antipruritic agent in a form of plaster and transdermal delivery system

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BB BG BR BY CA CH CN CZ DE DE DK DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1996927180

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2228034

Country of ref document: CA

Ref country code: CA

Ref document number: 2228034

Kind code of ref document: A

Format of ref document f/p: F

Ref country code: JP

Ref document number: 1997 507419

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1996927180

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1996927180

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: GB

Free format text: 19960726 A 9801409