CA2277366A1 - Transdermal, acetylsalicylic acid-containing therapeutic system with reinforced resorption - Google Patents
Transdermal, acetylsalicylic acid-containing therapeutic system with reinforced resorption Download PDFInfo
- Publication number
- CA2277366A1 CA2277366A1 CA002277366A CA2277366A CA2277366A1 CA 2277366 A1 CA2277366 A1 CA 2277366A1 CA 002277366 A CA002277366 A CA 002277366A CA 2277366 A CA2277366 A CA 2277366A CA 2277366 A1 CA2277366 A1 CA 2277366A1
- Authority
- CA
- Canada
- Prior art keywords
- limonene
- acetylsalicylic acid
- therapeutic system
- dimethylisosorbide
- 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.)
- Abandoned
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
- 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
- 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
Abstract
A transdermal, acetylsalicylic acid-containing therapeutic system has a substantially active substance- and humidity-impervious backing layer, an active substance reservoir and if required a detachable protecting layer. This transdermal therapeutic system is characterised by a limonene and dimethyl isosorbide content in a mixing ratio of at least 50 g limonene for 50 g dimethyl isosorbide in the area of the active substance.
Description
w Acetylsalicylic acid-containing transdermal therapeutic system with absorption enhancement The invention relates to an acetylsalicylic acid-containing transdermal therapeutic system with an essentially active ingredient- and moisture-impermeable backing layer, an active ingredient reservoir and, where appropriate, a redetachable protective layer.
Transdermal therapeutic systems (TTS) have already been launched on the market in the medicinal treatment of a number of disorders.
The ability in principle of the active ingredient acetyl-salicylic acid to permeate through the human skin and thus be suitable as ingredient of transdermal therapeutic systems is also known. Thus, Rougier et al. (J. Pharm. Sci.
176, 451-454, 1987) have already described the (rather low) dependence of the rate of acetylsalicylic acid uptake into the skin on the selected area of skin.
Acetylsalicylic acid is a relatively safe medicinal substance with a high therapeutic index. In very high doses (more than one gram a day) it is used as antirheumatic agent, in intermediate doses (250-500 mg) as antipyretic/analgesic and in low dosage (30 to 150 mg per day) as platelet aggregation inhibitor. Acetylsalicylic acid is a substance which melts at a low temperature (about 139°C) and shows marked volatility at this temperature.
Because of the unstable ester group, acetylsalicylic acid is susceptible to hydrolysis and transesterification.
Various stabilization methods have therefore already been considered, such as elimination of water, alcohols and esters as possible partners in a transesterification or hydrolysis reaction; addition of acetic acid or acetic anhydride or adjustment to pH 2-3. US-A 4,228,162 also mentions dimethylisosorbide as stabilizing solvent.
A major impediment of the development of acetylsalicylic acid-containing pharmaceutically effective transdermal therapeutic systems is moreover the low permeability, by comparison with the high therapeutic daily dose reguired, of the active ingredient through the skin. A large number of permeation accelerants have therefore already been proposed as additives, such as atones, carboxylic esters, surface-active substances etc.
US-A 5,164,416 also indicates limonene as permeation-enhancing substance for acetylsalicylic acid but, according to this, its use is restricted to the simultaneous addition of a possibly irritating alkaline additive. Furthermore the permeation rates which can be achieved for acetylsalicylic acid - following this teaching - are still insufficiently high.
It has now been found, surprisingly, that combined addition of limonene and dimethylisosorbide in particular ratios of amounts leads to a considerable improvement, which was not predictable, in acetylsalicylic acid permeation through the skin.
Accordingly, the transdermal therapeutic system according to the invention of the type mentioned at the outset is essentially characterized by a content of limonene and dimethylisosorbide in a mixing ratio of at least 50:50 (g/g) limonene to dimethylisosorbide in the active ingredient-active region.
This solution to the problem is surprising inasmuch as the route to a medicinal form with better bioavailability leads for the skilled person via basic substances which are good solvents, whereas limonene shows an extremely low solubility for acetylsalicylic acid - even on addition of dimethylisosorbide.
Particular features of the invention are evident from the claims and the following description.
The principle according to the invention can be utilized both in matrix systems and in reservoir/membrane systems.
It is also immaterial which polymers, resins and possibly other additives are added as long as the formulation is suitable for delivering the basic substances acetyl-salicylic acid, limonene and dimethylisosorbide to the skin.
In the simplest case it is possible for all three charac-terizing starting materials to be dispersed or dissolved in a solution of basic polymers, and for the mixture to be coated onto a suitable substrata, as a rule a siliconized thermoplastic sheet and, after evaporation of the solvent contents, where appropriate intensified by input of heat, to be covered with another sheet which forms the later rear side of the transdermal therapeutic system. Transdermal therapeutic systems are obtained from such a laminate by cutting out flat structures with the required geometric shape (circle, rounded rectangle etc.).
However, further embodiments may comprise forming a two-layer matrix consisting of a layer on the skin side, which contains the active ingredient in dispersed or dissolved form, and a second layer facing away from the skin, which contains limonene and dimethylisosorbide in the desired mixing ratio. These design variants ate, however, only the simplest of a number of possible conceptions of the system known to the skilled person. Thus, matrix systems with more than two layers are, of course, possible and, where appropriate, further active ingredients can be provided.
Suitable basic 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 indicates the wide applica-bility of the principle according to the invention.
The mixing ratio of limonene to dimethylisosorbide is, in particular, in the range from 50:50 to 99:1, preferably from 85:15 to 95:5 and specifically in the region of 90:10.
It is moreover possible and expedient to provide a limonene content which is of the order of magnitude of the acetyl-salicylic acid concentration.
Example 1:
20 g of micronized acetylsalicylic acid 30 g of limonene and 1 g of dimethylisosorbide are dissolved or dispersed in 600 g of an acrylate copolymer solution (solids content: 50% g/g).
The composition is coated onto a siliconized polyester sheet (100 ~t~m thick) to result in a layer with a weight per unit area of 150 g per ma. Drying takes place under mild conditions by storing at room temperature in the air for hours. The matrix obtained in this way is laminated with another sheet (polyester sheet 15 dun thick), and punches are used to cut out circles with a size of 20 cm2.
This results in transdermal therapeutic systems which can be applied to the skin directly after detachment of the siliconized polyester sheet in order to produce the desired therapeutic effect.
Example 2:
1.) 20 g of micronized acetylsalicylic acid are dispersed in 160 g of an acrylate copolymer solution (solids content:
50% g/g). The composition is coated onto a siliconized polyester sheet (100 ~tm thick) to result in a layer with a weight per unit area of 52 g/ma. Drying takes place by storing at room temperature in the air for 10 hours. The matrix obtained in this way is laminated with another sheet (polyester sheet 15 ~tm thick).
2.) 20 g of micronized acetylsalicylic acid are dispersed in 160 g of an acrylate copolymer solution (solids content:
50% g/g). The composition is coated onto a siliconized polyester sheet (100 Etm thick) to result in a layer with a weight per unit area of 93 g/m~. Drying takes place by storing at room temperature is the air for 10 hours.
A circular disc of fabric (cotton) 2.5g cma in size is applied to the adhesive area of the laminate from (2).
8.5 mg of a mixture of 10% (g/g) dimethylisosorbide and 90%
(g/g) limonene, which has previously been saturated with acetylsalicylic acid by stirring at room temperature for hours and then filtering, are applied dropwise to the disc of fabric. Laminate from (1) and disc of fabric are covered on the adhesive side with layer (2) so as to result in a sandwich of polyester sheet (15 Eun), 52 g/ma poly-acrylate with acetylsalicylic acid, doped disc of fabric 2.54 cmZ and 93 g/ma polyacrylate with acetylsalicylic acid, which is then covered on the adhesive side by a siliconized polyester protective sheet with an abhesive action.
Transdermal therapeutic systems (TTS) have already been launched on the market in the medicinal treatment of a number of disorders.
The ability in principle of the active ingredient acetyl-salicylic acid to permeate through the human skin and thus be suitable as ingredient of transdermal therapeutic systems is also known. Thus, Rougier et al. (J. Pharm. Sci.
176, 451-454, 1987) have already described the (rather low) dependence of the rate of acetylsalicylic acid uptake into the skin on the selected area of skin.
Acetylsalicylic acid is a relatively safe medicinal substance with a high therapeutic index. In very high doses (more than one gram a day) it is used as antirheumatic agent, in intermediate doses (250-500 mg) as antipyretic/analgesic and in low dosage (30 to 150 mg per day) as platelet aggregation inhibitor. Acetylsalicylic acid is a substance which melts at a low temperature (about 139°C) and shows marked volatility at this temperature.
Because of the unstable ester group, acetylsalicylic acid is susceptible to hydrolysis and transesterification.
Various stabilization methods have therefore already been considered, such as elimination of water, alcohols and esters as possible partners in a transesterification or hydrolysis reaction; addition of acetic acid or acetic anhydride or adjustment to pH 2-3. US-A 4,228,162 also mentions dimethylisosorbide as stabilizing solvent.
A major impediment of the development of acetylsalicylic acid-containing pharmaceutically effective transdermal therapeutic systems is moreover the low permeability, by comparison with the high therapeutic daily dose reguired, of the active ingredient through the skin. A large number of permeation accelerants have therefore already been proposed as additives, such as atones, carboxylic esters, surface-active substances etc.
US-A 5,164,416 also indicates limonene as permeation-enhancing substance for acetylsalicylic acid but, according to this, its use is restricted to the simultaneous addition of a possibly irritating alkaline additive. Furthermore the permeation rates which can be achieved for acetylsalicylic acid - following this teaching - are still insufficiently high.
It has now been found, surprisingly, that combined addition of limonene and dimethylisosorbide in particular ratios of amounts leads to a considerable improvement, which was not predictable, in acetylsalicylic acid permeation through the skin.
Accordingly, the transdermal therapeutic system according to the invention of the type mentioned at the outset is essentially characterized by a content of limonene and dimethylisosorbide in a mixing ratio of at least 50:50 (g/g) limonene to dimethylisosorbide in the active ingredient-active region.
This solution to the problem is surprising inasmuch as the route to a medicinal form with better bioavailability leads for the skilled person via basic substances which are good solvents, whereas limonene shows an extremely low solubility for acetylsalicylic acid - even on addition of dimethylisosorbide.
Particular features of the invention are evident from the claims and the following description.
The principle according to the invention can be utilized both in matrix systems and in reservoir/membrane systems.
It is also immaterial which polymers, resins and possibly other additives are added as long as the formulation is suitable for delivering the basic substances acetyl-salicylic acid, limonene and dimethylisosorbide to the skin.
In the simplest case it is possible for all three charac-terizing starting materials to be dispersed or dissolved in a solution of basic polymers, and for the mixture to be coated onto a suitable substrata, as a rule a siliconized thermoplastic sheet and, after evaporation of the solvent contents, where appropriate intensified by input of heat, to be covered with another sheet which forms the later rear side of the transdermal therapeutic system. Transdermal therapeutic systems are obtained from such a laminate by cutting out flat structures with the required geometric shape (circle, rounded rectangle etc.).
However, further embodiments may comprise forming a two-layer matrix consisting of a layer on the skin side, which contains the active ingredient in dispersed or dissolved form, and a second layer facing away from the skin, which contains limonene and dimethylisosorbide in the desired mixing ratio. These design variants ate, however, only the simplest of a number of possible conceptions of the system known to the skilled person. Thus, matrix systems with more than two layers are, of course, possible and, where appropriate, further active ingredients can be provided.
Suitable basic 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 indicates the wide applica-bility of the principle according to the invention.
The mixing ratio of limonene to dimethylisosorbide is, in particular, in the range from 50:50 to 99:1, preferably from 85:15 to 95:5 and specifically in the region of 90:10.
It is moreover possible and expedient to provide a limonene content which is of the order of magnitude of the acetyl-salicylic acid concentration.
Example 1:
20 g of micronized acetylsalicylic acid 30 g of limonene and 1 g of dimethylisosorbide are dissolved or dispersed in 600 g of an acrylate copolymer solution (solids content: 50% g/g).
The composition is coated onto a siliconized polyester sheet (100 ~t~m thick) to result in a layer with a weight per unit area of 150 g per ma. Drying takes place under mild conditions by storing at room temperature in the air for hours. The matrix obtained in this way is laminated with another sheet (polyester sheet 15 dun thick), and punches are used to cut out circles with a size of 20 cm2.
This results in transdermal therapeutic systems which can be applied to the skin directly after detachment of the siliconized polyester sheet in order to produce the desired therapeutic effect.
Example 2:
1.) 20 g of micronized acetylsalicylic acid are dispersed in 160 g of an acrylate copolymer solution (solids content:
50% g/g). The composition is coated onto a siliconized polyester sheet (100 ~tm thick) to result in a layer with a weight per unit area of 52 g/ma. Drying takes place by storing at room temperature in the air for 10 hours. The matrix obtained in this way is laminated with another sheet (polyester sheet 15 ~tm thick).
2.) 20 g of micronized acetylsalicylic acid are dispersed in 160 g of an acrylate copolymer solution (solids content:
50% g/g). The composition is coated onto a siliconized polyester sheet (100 Etm thick) to result in a layer with a weight per unit area of 93 g/m~. Drying takes place by storing at room temperature is the air for 10 hours.
A circular disc of fabric (cotton) 2.5g cma in size is applied to the adhesive area of the laminate from (2).
8.5 mg of a mixture of 10% (g/g) dimethylisosorbide and 90%
(g/g) limonene, which has previously been saturated with acetylsalicylic acid by stirring at room temperature for hours and then filtering, are applied dropwise to the disc of fabric. Laminate from (1) and disc of fabric are covered on the adhesive side with layer (2) so as to result in a sandwich of polyester sheet (15 Eun), 52 g/ma poly-acrylate with acetylsalicylic acid, doped disc of fabric 2.54 cmZ and 93 g/ma polyacrylate with acetylsalicylic acid, which is then covered on the adhesive side by a siliconized polyester protective sheet with an abhesive action.
7.10 cm~ circles are cut of this laminate in such a way that the disc of fabric is located in the middle. After application to excited rat skin, the permeation is determined in vitro.
The average permeation found after 48 hours was 632.6 ~,tg/cma acetylsalicylic acid.
Example 3 (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cm2 in size is applied to the adhesive area of the laminate from (2).
The average permeation found after 48 hours was 632.6 ~,tg/cma acetylsalicylic acid.
Example 3 (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cm2 in size is applied to the adhesive area of the laminate from (2).
8.5 mg of pure dimethylisosorbide which has previously been saturated with acetylsalicylic acid by stirriag at room temperature for 5 hours and then filtering, are applied dropwise to the disc of fabric. Laminate from (1) and disc of fabric are cut out into 7.10 cma specimens in analogy to Example 2. A determination of the permeation of excised rat skin was also carried out in the same way.
The average permeation found after 48 hours was 130.4 ~g/cma acetylsalicylic acid.
Example 4: (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cma in size is applied to the adhesive area of the laminate from (2).
8.5 mg of pure limonene which has previously been saturated with acetylsalicylic acid by stirring at room temperature for 5 hours and then filtering, are applied dropwise to the disc of fabric. Laminate from (1) and disc of fabric are cut out into 7.10 cmZ specimens in analogy to Example 2. A
_ ') _ determination of the perzneation of excised rat skin was also carried out in the same way.
The average permeation found after 48 hours was 253.3 ~,g/cma acetylsalicylic acid.
Example 5: (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cma in size is applied to the adhesive area of the laminate from (2). No dropwise application of medium takes place. Laminate from (1) and disc of fabric are cut out into 7.10 cma specimens in analogy to Example 2. A determination of the permeation of excised rat skin was also carried out in the same way.
The average permeation found after 48 hours was 52.9 ~.g/cma acetylsalicylic acid.
Comparison of the permeation results for Examples 2 to 5 clearly shows the superiority of the system according to the invention.
The average permeation found after 48 hours was 130.4 ~g/cma acetylsalicylic acid.
Example 4: (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cma in size is applied to the adhesive area of the laminate from (2).
8.5 mg of pure limonene which has previously been saturated with acetylsalicylic acid by stirring at room temperature for 5 hours and then filtering, are applied dropwise to the disc of fabric. Laminate from (1) and disc of fabric are cut out into 7.10 cmZ specimens in analogy to Example 2. A
_ ') _ determination of the perzneation of excised rat skin was also carried out in the same way.
The average permeation found after 48 hours was 253.3 ~,g/cma acetylsalicylic acid.
Example 5: (example comparing with Example 2):
Layer 1 and 2 are produced in accordance with Example 2.
A circular disc of fabric (cotton) 2.54 cma in size is applied to the adhesive area of the laminate from (2). No dropwise application of medium takes place. Laminate from (1) and disc of fabric are cut out into 7.10 cma specimens in analogy to Example 2. A determination of the permeation of excised rat skin was also carried out in the same way.
The average permeation found after 48 hours was 52.9 ~.g/cma acetylsalicylic acid.
Comparison of the permeation results for Examples 2 to 5 clearly shows the superiority of the system according to the invention.
Claims (6)
1. Acetylsalicylic acid-containing transdermal therapeutic system with an essentially active ingredient- and moisture-impermeable backing layer, an active ingredient reservoir and, where appropriate, a redetachable protective layer, characterized by a content of limonene and dimethylisosorbide in a mixing ratio of at least 50:50 (g/g) limonene to dimethyl-isosorbide in the active ingredient-active region.
2. Transdermal therapeutic system according to Claim 1, characterized by a monolayer or multilayer matrix as active ingredient reservoir, of which at least one layer contains limonene and dimethylisosorbide in a mixing ratio of 50:50 to 99:1 (limonene to dimethyl-isosorbide).
3. Transdermal therapeutic system according to Claim 1 or 2, characterized by a mixing ratio of limonene to dimethylisosorbide of 85:15 to 95:5 (g/g), in particular 90:10.
4. Transdermal therapeutic system according to any of the preceding claims, characterized in that acetylsalicylic acid, limonene and dimethylisosorbide are present dissolved or dispersed in basic polymers.
5. Transdermal therapeutic system according to any of the preceding claims, characterized by an at least two-layer matrix whose layer facing away from the skin contains limonene and dimethylisosorbide in the stated mixing ratio.
6. Transdermal therapeutic system according to any of the preceding claims, characterized by a limonene content of the order of magnitude of the acetylsalicylic acid concentration.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19701059A DE19701059C2 (en) | 1997-01-15 | 1997-01-15 | Transdermal therapeutic system with absorption enhancement containing acetylsalicylic acid |
| DE19701059.8 | 1997-01-15 | ||
| PCT/EP1998/000013 WO1998031348A1 (en) | 1997-01-15 | 1998-01-03 | Transdermal, acetylsalicylic acid-containing therapeutic system with reinforced resorption |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2277366A1 true CA2277366A1 (en) | 1998-07-23 |
Family
ID=7817375
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002277366A Abandoned CA2277366A1 (en) | 1997-01-15 | 1998-01-03 | Transdermal, acetylsalicylic acid-containing therapeutic system with reinforced resorption |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1023053A1 (en) |
| JP (1) | JP2001508069A (en) |
| KR (1) | KR20000070228A (en) |
| AU (1) | AU726094B2 (en) |
| CA (1) | CA2277366A1 (en) |
| DE (1) | DE19701059C2 (en) |
| NO (1) | NO993435L (en) |
| WO (1) | WO1998031348A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19949202A1 (en) * | 1999-10-13 | 2001-05-03 | Lohmann Therapie Syst Lts | Transdermal therapeutic system for the delivery of acetylsalicylic acid and / or salicylic acid |
| DE19949252B4 (en) * | 1999-10-13 | 2004-02-12 | Lts Lohmann Therapie-Systeme Ag | Use of a superficial therapeutic system for the topical application of acetylsalicylic acid for the treatment of acne disorders and process for its preparation |
| DE19959913A1 (en) * | 1999-12-11 | 2001-06-28 | Lohmann Therapie Syst Lts | Transdermal system for the treatment of migraines containing acetylsalicylic acid |
| KR100448469B1 (en) * | 2001-10-26 | 2004-09-13 | 신풍제약주식회사 | Transdermal composition and device of anti-inflammatory agents |
| AU2002342241B2 (en) | 2001-11-01 | 2007-07-19 | Novartis Ag | Spray drying methods and compositions thereof |
| DE10338162B3 (en) † | 2003-08-20 | 2005-06-02 | Haldex Brake Products Gmbh | Method for operating a compressed air procurement system of a motor vehicle and compressed air treatment device |
| DE102005033543A1 (en) * | 2005-07-14 | 2007-01-18 | Grünenthal GmbH | A fragrance-containing transdermal therapeutic system |
| DE102005050431A1 (en) * | 2005-10-21 | 2007-04-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for the administration of lipophilic and / or less skin-permeable active ingredients |
| IT202000014578A1 (en) * | 2020-06-18 | 2021-12-18 | Poli Md S R L | MEDICAL DEVICE INCLUDING ACETYL SALICYLIC ACID |
Family Cites Families (4)
| 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 |
| DE4332094C2 (en) * | 1993-09-22 | 1995-09-07 | Lohmann Therapie Syst Lts | Active substance plaster which can be produced without solvent and process for its preparation |
| DE4332093C2 (en) * | 1993-09-22 | 1995-07-13 | Lohmann Therapie Syst Lts | Transdermal therapeutic system with the active ingredient acetylsalicylic acid and process for its preparation |
-
1997
- 1997-01-15 DE DE19701059A patent/DE19701059C2/en not_active Expired - Fee Related
-
1998
- 1998-01-03 EP EP98902976A patent/EP1023053A1/en not_active Withdrawn
- 1998-01-03 CA CA002277366A patent/CA2277366A1/en not_active Abandoned
- 1998-01-03 WO PCT/EP1998/000013 patent/WO1998031348A1/en not_active Application Discontinuation
- 1998-01-03 AU AU59862/98A patent/AU726094B2/en not_active Ceased
- 1998-01-03 KR KR1019997006454A patent/KR20000070228A/en not_active Application Discontinuation
- 1998-01-03 JP JP53137698A patent/JP2001508069A/en active Pending
-
1999
- 1999-07-12 NO NO993435A patent/NO993435L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998031348A1 (en) | 1998-07-23 |
| AU5986298A (en) | 1998-08-07 |
| DE19701059A1 (en) | 1998-07-16 |
| KR20000070228A (en) | 2000-11-25 |
| NO993435D0 (en) | 1999-07-12 |
| DE19701059C2 (en) | 2000-12-21 |
| NO993435L (en) | 1999-07-12 |
| AU726094B2 (en) | 2000-11-02 |
| JP2001508069A (en) | 2001-06-19 |
| EP1023053A1 (en) | 2000-08-02 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20030103 |