CA2006425C - Transdermal therapeutical system comprising norpseudoephedrine as active component - Google Patents
Transdermal therapeutical system comprising norpseudoephedrine as active componentInfo
- Publication number
- CA2006425C CA2006425C CA002006425A CA2006425A CA2006425C CA 2006425 C CA2006425 C CA 2006425C CA 002006425 A CA002006425 A CA 002006425A CA 2006425 A CA2006425 A CA 2006425A CA 2006425 C CA2006425 C CA 2006425C
- Authority
- CA
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- Prior art keywords
- therapeutic composition
- composition according
- transdermal therapeutic
- softener
- polymer comprises
- 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.)
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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
- 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
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention relates to a transdermal therapeutical system for the administration of an active substance to the skin via a backing layer being impermeable to active sub-stances, a reservoir layer, and optionally a removable pro-tective layer, the reservoir layer of which is pressure-sen-sitive adhesive and comprises 10-90%-wt polymeric material, 0-30%-wt softener, and 0.1-20%-wt of a norpseudoephedrine.
Description
D E S C R I P T I O N
The present invention relates to a transdermal therapeutical system comprising norpseudoephedrine as active component.
The amphetamines, the chemical group many of the antiadi-pogenics belong to, were discovered as early as in the nine-teen thirties, however were prescribed only as remedy against fatigue. Even later, it was recognized that these pharmaceuticals had another therapeutically useful effect -they reduce the sensation of hunger. It was achieved by systematic synthesis of the pharmaceutical to develop sub-stances which emphasize the reduction of the feeling of hunger, while neglecting the stimulating component. Neverthe-less, the following aspects have to be considered in the application of such antiadipogenics:
- They must not be combined with certain other medicines (neither with alcohol) - Drug habituation and drug addiction have to be observed - Intravenous injections are to be avoided due to the danger of induction of blood leveI peaks.
$~
~ ` ~00~425 Legislation as well as the pharmaceutical industry take into account these facts, on the-one hand in that liquid drugs are sold only on prescription while the solid ones are OTC--pharmaceuticals, and, on the other hand, in that due to the development of orally adminstrable controlled release drugs the dosage of the antiadipogenics may be réduced, the blood levels, however, may be kept constant. Since, nowadays, the medical profession is of the opinion that the administration form contributes to the addiction to a substance (a constant blood level is by far more favourable as the rapid change of blood level peaks with overdose and intervals with under-supply), it is obvious to develop controlled release drugs which create an even better constant concentration level than the oral ones are able to provide. Since, although the common oral forms of controlled release drugs are a masterly achievement of galenic technology, which under in-vitro-con-ditions, i.e. in artificial gastric or intestinal juices, create optimum release, they cannot guarantee constant blood levels, since the resorption of drug substance from the gastrointestinal tract is considerably influenced by the evacuation time of the stomach which is retarded by the ingestion of food as a function of the volume and the compo-sition of the nourishment. Furthermore, pH-value shifs in the stomach occur during the ingestion and the diffusion effective gradients decrease due to mixing of the gastric juice with the chyme. The significance of the pH-value condi-. Z006425 ~_ 3 tions within the stomach for the gastral resorption is under-lined by tests in which the gastric juice was alkalized. It was proved in aminal tests that after alkalization of the stomach content with NaHC03 to pH : 8.0, the resorption from the stomach was reduced in the case of weak acids correspond-ing to the pKa-value and increased in the case of weak bases. Since amphetamines are bases of medium strength (pKa-value D-norpseudoephedrine : 8.9), the effect of the pH-value depending resorption is not distinctive, but it should not be neglected at all.
The use of so-called therapeutical systems is suitable for the creation of an active substance concentration which is as constant as possible; said therapeutical systems are defined as a drug containing device or administration form, respectively, which continuously releases a drug or several drugs at a predefined rate over a predetermined period of time onto a defined place of application (cf. Heilmann, "Therapeutische Systeme", 4th edition, Enke publishers, Stuttgart 1984, page 26). An oral therapeutical system, e.g., as described in EP 0 237 159, however, is no solution to the problem described, since bases of medium strength better dissolve in acidic gastric juice than in neutral gastric juice. Thus the release becomes pH-value dependent.
In US-PS 4,292,301 the transdermal release of ephedrine from ~ 4 2006425 28483-2 a non-adhesive polymeric matrix has been described, however, the ephedrine exhibits only a weak efficiency as antiadipogenic.
Thus it is the object of the present invention to provide norpseudoephedrine as antiadipogenic or an agent, respectively, in a form with which a by far improved, constant active substance level in contrast to the oral form of controlled release drugs is achieved, in order to overcome the disadvantages of the prior art.
According to the present invention this object is surprisingly achieved by a transdermal therapeutical system which releases an antiadipogenic to the skin via a backing layer being impermeable to active substances, a reservoir layer, and optionally a removable protective layer, and which is characterized in that the reservoir layer is pressure-sensitive adhesive and comprises 10-90%-wt polymeric material, 0-30%-wt softener, and 0.1-20%-wt norpseudoephedrine.
According to one aspect of the present invention there is provided a transdermal therapeutic composition including active compounds for the administration of an antiadipogenic to the skin comprising a backing layer being impermeable to the active compounds and a reservoir layer, wherein the reservoir layer is pressure-sensitive adhesive and comprises 10-90%-wt of polymer and 0.1-20%-wt norpseudoephedrine.
This solution is surprising all the more, since norpseudoephedrine has to be applied in daily dosages, and this normally cannot be achieved in acceptable ranges by transdermal therapeutical systems.
In this connection, the backing layer which is impermeable B
~)06425 ~_ 5 to active substances may consist of flexible or non-flexible material. Substances suitable for the production are polymer-ic foils or metal foils, such as aluminium foils which can be used alone or coated with a polymeric substrate. Textile fabrics may be used as well, if the components of the reser-voir, due to their physical properties, cannot penetrate through the fabrics. In a preferred embodiment the backing layer is a nonwoven fabric from a foil vapourized with alu-minium.
The reservoir layer consists of a polymeric matrix and the active substance, whereby the polymeric matrix guarantees the coherence of the system. The matrix consists of a basic polymer and optionally of common additives. The selection of the basic polymer depends on the chemical and physical pro-perties of the active substance used. Examples for polymers are rubber, rubber-like synthetic homopolymers, copolymers or block polymers, polyacrylic acid esters and their copoly-mers, polyurethanes, and silicones. In principle all poly-mers are suitable which are used in the production of pres-sure-sensitive adhesives and which are physiologically ac-ceptable. It is particularly preferred to use those polymers consisting of block copolymers on the basis of styrene and 1,3-dienes, polyisobutylenes, polymers of acrylate and/or methacrylate and esters of hydrogenated colophoniu~. In particular, linear styrene-isoprene block copolymers are used from the group of block copolymers on Z00~i425 .
the basis of styrene and 1,3-dienes.
Acrylate-copolymers of 2-ethylhexylacrylate, vinyl acetate, and acrylic acid with or without titane chelate ester are preferred as polymers on acrylate basis. Copolymers on the basis of dimethylaminoethyl methacrylates and neutral meth-acrylic acid esters are preferred as methacrylates. As esters of hydrogenated colophonium its methyl and glyceryl esters are particularly preferred.
The kind of possible additive depends on the polymer used and the active substance: According to their function they can be divided into softeners, tackifiers, stabilizers, carriers, diffusion and penetration regulating additives or fillers. Suitable physiologically acceptable substances are known to the man skilled in the art. The reservoir layer has such a self-adhesiveness that a constant contact to the skin is guaranteed.
Examples for suitable softeners are diesters of dicarboxylic acids, such as di-n-butyl adipate and triglycerides, parti-cularly medium chain triglycerides of the caprylic/capric acid of coconut oil. Further examples for suitable softeners are glycerol, ~Lu~ll~iol (1,2) etc., also vicinal aloohols and esters.
The removable protective layer, which is in contact with the ;~0~ 25 reservoir layer and is removed prior to application, for example consists of the same materials as are used for the production of the backing layer, provided that they are rendered removable, for example by way of a silicone treat-ment. Further detachable protective layers, e.g., are poly-tetrafluoroethylene, treated paper, cellophane, polyvinyl chloride, etc. If the laminate according to the present invention is cut into suitable sizes (plasters) prior to applying the protective layer, the dimensions of the protec-tive layer to be applied may have overlapping ends, so that they may be removed from the plaster more easily.
According to the present invention, norpseudoephedrine is used as antiadipogenic, since it exhibits the lowest ten-dency to dependence of all antiadipogenics.
The transdermal therapeutical system according to the present invention is produced in that the active substance together with the components of the pressure-sensitive reser-voir layer, optionally in solution, are homogeneously ad-mixed and coated onto the backing layer which is impermeable to the active substance, then optionally the solvent or solvents is/are removed. Subsequently, the adhesive layer is provided with a suitable protective layer.
The invention is illustrated but not limited by the follow-ing examples:
Preparation - Example 1:
4.3 g n-heptane and 15.7 g butanone are mixed. 4.0 g nor-pseudoephedrine, free base, is dissolved therein. After complete dissolution of the active substance there is added by portions 23.5 g of a glyceryl ester of completely hydro-genated colophonium, 15.5 g of a linear styrene-butadiene--styrene block copolymer, 3.9 g methyl ester of hydrogenated colophonium and 3.1 g triglycerides of the caprylic/capric acid of coconut oil ("medium chain triglycerides" DAB 8 (=
The German Pharmacopeia, 1978). Under elimination of light it is stirred up to complete dissolution (approximately 8 hours) and the solution obtained is coated onto a aluminized and siliconized polyethylene foil with a 300~m coating knife.
After removal of the solvent by drying at 50C in the drying channel for 25 minutes, the adhesive film is covered with a polyester foil of 15~. Sizes of 16cm2 and 50cm2, respective-ly, are punched with an adequate cutting tool and the edges are separated off. The diagram of the in-vitro-release is shown in figure 1. It shows the controlled active substance release from a 16 cm2 plaster in physiological saline.
Furthermore, a healthy volunteer wore a 50 cm2 plaster for 12 hours, which contains 52 mg norpseudoephedrine, free base, having an area weight of 130 g/m2. After removal of the system the residual content was determined at approxi-mately 17 mg, so that approximately 35 mg/50 cm2 have been diffused through human skin within 12 hours.
Thus, the therapeutically required value has been surpassed.
Preparation - Example 2:
25 g butanone and 15 g ethylacetate are mixed. 10.0 g nor-pseudoephedrine, free base, is dissolved therein. After complete dissolution of the active substance there is added by portions 17.5 g of a glyceryl ester of completely hydro-genated colophonium and 22.5 g of a linear styrene-butadiene--styrene block copolymer. Under elimination of light it is stirred up to complete dissolution (approximately 8 hours) and the solution obtained is coated onto a aluminized and siliconized polyethylene foil (thickness: 100 ,um) with a 350,um coating knife.
After removal of the solvent by drying at 50C in the drying channel for 25 minutes, the adhesive film is covered with a polyethylene foil (thickness: 15,um). Sizes of 16cm2 are punched with an adequate cutting tool and the edges are separated off. The diagram of the in-vitro-release is shown in figure 2. It shows the controlled release of the active ` ~ 2006425 substance from a 16 cm2 plaster in physiological saline.
Furthermore, the in-vitro penetration was determined with excised mice skin. It amounts to 9.8 mg/16 cm2 x 24 h and thus lies in the range of example 1 without the addition of a softener.
The present invention relates to a transdermal therapeutical system comprising norpseudoephedrine as active component.
The amphetamines, the chemical group many of the antiadi-pogenics belong to, were discovered as early as in the nine-teen thirties, however were prescribed only as remedy against fatigue. Even later, it was recognized that these pharmaceuticals had another therapeutically useful effect -they reduce the sensation of hunger. It was achieved by systematic synthesis of the pharmaceutical to develop sub-stances which emphasize the reduction of the feeling of hunger, while neglecting the stimulating component. Neverthe-less, the following aspects have to be considered in the application of such antiadipogenics:
- They must not be combined with certain other medicines (neither with alcohol) - Drug habituation and drug addiction have to be observed - Intravenous injections are to be avoided due to the danger of induction of blood leveI peaks.
$~
~ ` ~00~425 Legislation as well as the pharmaceutical industry take into account these facts, on the-one hand in that liquid drugs are sold only on prescription while the solid ones are OTC--pharmaceuticals, and, on the other hand, in that due to the development of orally adminstrable controlled release drugs the dosage of the antiadipogenics may be réduced, the blood levels, however, may be kept constant. Since, nowadays, the medical profession is of the opinion that the administration form contributes to the addiction to a substance (a constant blood level is by far more favourable as the rapid change of blood level peaks with overdose and intervals with under-supply), it is obvious to develop controlled release drugs which create an even better constant concentration level than the oral ones are able to provide. Since, although the common oral forms of controlled release drugs are a masterly achievement of galenic technology, which under in-vitro-con-ditions, i.e. in artificial gastric or intestinal juices, create optimum release, they cannot guarantee constant blood levels, since the resorption of drug substance from the gastrointestinal tract is considerably influenced by the evacuation time of the stomach which is retarded by the ingestion of food as a function of the volume and the compo-sition of the nourishment. Furthermore, pH-value shifs in the stomach occur during the ingestion and the diffusion effective gradients decrease due to mixing of the gastric juice with the chyme. The significance of the pH-value condi-. Z006425 ~_ 3 tions within the stomach for the gastral resorption is under-lined by tests in which the gastric juice was alkalized. It was proved in aminal tests that after alkalization of the stomach content with NaHC03 to pH : 8.0, the resorption from the stomach was reduced in the case of weak acids correspond-ing to the pKa-value and increased in the case of weak bases. Since amphetamines are bases of medium strength (pKa-value D-norpseudoephedrine : 8.9), the effect of the pH-value depending resorption is not distinctive, but it should not be neglected at all.
The use of so-called therapeutical systems is suitable for the creation of an active substance concentration which is as constant as possible; said therapeutical systems are defined as a drug containing device or administration form, respectively, which continuously releases a drug or several drugs at a predefined rate over a predetermined period of time onto a defined place of application (cf. Heilmann, "Therapeutische Systeme", 4th edition, Enke publishers, Stuttgart 1984, page 26). An oral therapeutical system, e.g., as described in EP 0 237 159, however, is no solution to the problem described, since bases of medium strength better dissolve in acidic gastric juice than in neutral gastric juice. Thus the release becomes pH-value dependent.
In US-PS 4,292,301 the transdermal release of ephedrine from ~ 4 2006425 28483-2 a non-adhesive polymeric matrix has been described, however, the ephedrine exhibits only a weak efficiency as antiadipogenic.
Thus it is the object of the present invention to provide norpseudoephedrine as antiadipogenic or an agent, respectively, in a form with which a by far improved, constant active substance level in contrast to the oral form of controlled release drugs is achieved, in order to overcome the disadvantages of the prior art.
According to the present invention this object is surprisingly achieved by a transdermal therapeutical system which releases an antiadipogenic to the skin via a backing layer being impermeable to active substances, a reservoir layer, and optionally a removable protective layer, and which is characterized in that the reservoir layer is pressure-sensitive adhesive and comprises 10-90%-wt polymeric material, 0-30%-wt softener, and 0.1-20%-wt norpseudoephedrine.
According to one aspect of the present invention there is provided a transdermal therapeutic composition including active compounds for the administration of an antiadipogenic to the skin comprising a backing layer being impermeable to the active compounds and a reservoir layer, wherein the reservoir layer is pressure-sensitive adhesive and comprises 10-90%-wt of polymer and 0.1-20%-wt norpseudoephedrine.
This solution is surprising all the more, since norpseudoephedrine has to be applied in daily dosages, and this normally cannot be achieved in acceptable ranges by transdermal therapeutical systems.
In this connection, the backing layer which is impermeable B
~)06425 ~_ 5 to active substances may consist of flexible or non-flexible material. Substances suitable for the production are polymer-ic foils or metal foils, such as aluminium foils which can be used alone or coated with a polymeric substrate. Textile fabrics may be used as well, if the components of the reser-voir, due to their physical properties, cannot penetrate through the fabrics. In a preferred embodiment the backing layer is a nonwoven fabric from a foil vapourized with alu-minium.
The reservoir layer consists of a polymeric matrix and the active substance, whereby the polymeric matrix guarantees the coherence of the system. The matrix consists of a basic polymer and optionally of common additives. The selection of the basic polymer depends on the chemical and physical pro-perties of the active substance used. Examples for polymers are rubber, rubber-like synthetic homopolymers, copolymers or block polymers, polyacrylic acid esters and their copoly-mers, polyurethanes, and silicones. In principle all poly-mers are suitable which are used in the production of pres-sure-sensitive adhesives and which are physiologically ac-ceptable. It is particularly preferred to use those polymers consisting of block copolymers on the basis of styrene and 1,3-dienes, polyisobutylenes, polymers of acrylate and/or methacrylate and esters of hydrogenated colophoniu~. In particular, linear styrene-isoprene block copolymers are used from the group of block copolymers on Z00~i425 .
the basis of styrene and 1,3-dienes.
Acrylate-copolymers of 2-ethylhexylacrylate, vinyl acetate, and acrylic acid with or without titane chelate ester are preferred as polymers on acrylate basis. Copolymers on the basis of dimethylaminoethyl methacrylates and neutral meth-acrylic acid esters are preferred as methacrylates. As esters of hydrogenated colophonium its methyl and glyceryl esters are particularly preferred.
The kind of possible additive depends on the polymer used and the active substance: According to their function they can be divided into softeners, tackifiers, stabilizers, carriers, diffusion and penetration regulating additives or fillers. Suitable physiologically acceptable substances are known to the man skilled in the art. The reservoir layer has such a self-adhesiveness that a constant contact to the skin is guaranteed.
Examples for suitable softeners are diesters of dicarboxylic acids, such as di-n-butyl adipate and triglycerides, parti-cularly medium chain triglycerides of the caprylic/capric acid of coconut oil. Further examples for suitable softeners are glycerol, ~Lu~ll~iol (1,2) etc., also vicinal aloohols and esters.
The removable protective layer, which is in contact with the ;~0~ 25 reservoir layer and is removed prior to application, for example consists of the same materials as are used for the production of the backing layer, provided that they are rendered removable, for example by way of a silicone treat-ment. Further detachable protective layers, e.g., are poly-tetrafluoroethylene, treated paper, cellophane, polyvinyl chloride, etc. If the laminate according to the present invention is cut into suitable sizes (plasters) prior to applying the protective layer, the dimensions of the protec-tive layer to be applied may have overlapping ends, so that they may be removed from the plaster more easily.
According to the present invention, norpseudoephedrine is used as antiadipogenic, since it exhibits the lowest ten-dency to dependence of all antiadipogenics.
The transdermal therapeutical system according to the present invention is produced in that the active substance together with the components of the pressure-sensitive reser-voir layer, optionally in solution, are homogeneously ad-mixed and coated onto the backing layer which is impermeable to the active substance, then optionally the solvent or solvents is/are removed. Subsequently, the adhesive layer is provided with a suitable protective layer.
The invention is illustrated but not limited by the follow-ing examples:
Preparation - Example 1:
4.3 g n-heptane and 15.7 g butanone are mixed. 4.0 g nor-pseudoephedrine, free base, is dissolved therein. After complete dissolution of the active substance there is added by portions 23.5 g of a glyceryl ester of completely hydro-genated colophonium, 15.5 g of a linear styrene-butadiene--styrene block copolymer, 3.9 g methyl ester of hydrogenated colophonium and 3.1 g triglycerides of the caprylic/capric acid of coconut oil ("medium chain triglycerides" DAB 8 (=
The German Pharmacopeia, 1978). Under elimination of light it is stirred up to complete dissolution (approximately 8 hours) and the solution obtained is coated onto a aluminized and siliconized polyethylene foil with a 300~m coating knife.
After removal of the solvent by drying at 50C in the drying channel for 25 minutes, the adhesive film is covered with a polyester foil of 15~. Sizes of 16cm2 and 50cm2, respective-ly, are punched with an adequate cutting tool and the edges are separated off. The diagram of the in-vitro-release is shown in figure 1. It shows the controlled active substance release from a 16 cm2 plaster in physiological saline.
Furthermore, a healthy volunteer wore a 50 cm2 plaster for 12 hours, which contains 52 mg norpseudoephedrine, free base, having an area weight of 130 g/m2. After removal of the system the residual content was determined at approxi-mately 17 mg, so that approximately 35 mg/50 cm2 have been diffused through human skin within 12 hours.
Thus, the therapeutically required value has been surpassed.
Preparation - Example 2:
25 g butanone and 15 g ethylacetate are mixed. 10.0 g nor-pseudoephedrine, free base, is dissolved therein. After complete dissolution of the active substance there is added by portions 17.5 g of a glyceryl ester of completely hydro-genated colophonium and 22.5 g of a linear styrene-butadiene--styrene block copolymer. Under elimination of light it is stirred up to complete dissolution (approximately 8 hours) and the solution obtained is coated onto a aluminized and siliconized polyethylene foil (thickness: 100 ,um) with a 350,um coating knife.
After removal of the solvent by drying at 50C in the drying channel for 25 minutes, the adhesive film is covered with a polyethylene foil (thickness: 15,um). Sizes of 16cm2 are punched with an adequate cutting tool and the edges are separated off. The diagram of the in-vitro-release is shown in figure 2. It shows the controlled release of the active ` ~ 2006425 substance from a 16 cm2 plaster in physiological saline.
Furthermore, the in-vitro penetration was determined with excised mice skin. It amounts to 9.8 mg/16 cm2 x 24 h and thus lies in the range of example 1 without the addition of a softener.
Claims (16)
1. A transdermal therapeutic composition including active compounds for the administration of an antiadipogenic to the skin comprising a backing layer being impermeable to the active com-pounds and a reservoir layer, wherein the reservoir layer is pressure-sensitive adhesive and comprises 10-90%-wt of polymer and 0.1-20%-wt norpseudoephedrine.
2. A transdermal therapeutic composition according to claim 1 further comprising a removable protective layer.
3. A transdermal therapeutic composition according to claim 1 wherein the reservoir layer further comprises up to 30%
by wt of a softener.
by wt of a softener.
4. A transdermal therapeutic composition according to claim 1, 2 or 3 wherein the polymer is selected from the group consisting of block copolymers of styrene and 1,3-dienes, polyiso-butylenes, polymers of acrylate and/or methacrylate, and esters of hydrogenated colophonium.
5. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises linear styrene-isoprene block copolymer.
6. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises linear styrene-butadiene block copolymer.
7. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises a self-crosslinking acrylate copolymer of 2-ethylhexyl acrylate, vinyl acetate, acrylic acid, and titane chelate ester.
8. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises a non-self-crosslinking acrylate copolymer of 2-ethylhexyl acrylate, vinyl acetate, and acrylic acid.
9. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises a copolymer of dimethylamino-ethyl methacrylate and neutral methacrylic acid ester.
10. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises the methylester of hydrogen-ated colophonium.
11. A transdermal therapeutic composition according to claim 4 wherein the polymer comprises the glyceryl ester of hydrogenated colophonium.
12. A transdermal therapeutic composition according to claim 3 wherein the softener is selected from the group consisting of vicinal alcohols and esters.
13. A transdermal therapeutic composition according to claim 3 wherein the softener is propanediol-1,2.
14. A transdermal therapeutic composition according to claim 3 wherein the softener is di-n-butyl adipate.
15. A transdermal therapeutic composition according to claim 3 wherein the softener is a triglyceride.
16. A transdermal therapeutic composition according to claim 3 wherein the softener is glycerol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3843237A DE3843237A1 (en) | 1988-12-22 | 1988-12-22 | TRANSDERMAL THERAPEUTIC SYSTEM WITH AN ANTIADIPOSITUM AS AN ACTIVE INGREDIENT |
| DEP3843237.4 | 1988-12-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2006425A1 CA2006425A1 (en) | 1990-06-22 |
| CA2006425C true CA2006425C (en) | 1995-09-05 |
Family
ID=6369853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002006425A Expired - Fee Related CA2006425C (en) | 1988-12-22 | 1989-12-21 | Transdermal therapeutical system comprising norpseudoephedrine as active component |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0374725B1 (en) |
| JP (1) | JP2602108B2 (en) |
| KR (1) | KR950015055B1 (en) |
| AT (1) | ATE93147T1 (en) |
| AU (1) | AU614208B2 (en) |
| CA (1) | CA2006425C (en) |
| CS (1) | CS275356B2 (en) |
| DD (1) | DD290581A5 (en) |
| DE (2) | DE3843237A1 (en) |
| DK (1) | DK651089A (en) |
| ES (1) | ES2045369T3 (en) |
| FI (1) | FI95772C (en) |
| HU (1) | HU203280B (en) |
| IE (1) | IE63878B1 (en) |
| IL (1) | IL92678A (en) |
| MY (1) | MY105074A (en) |
| NO (1) | NO178784C (en) |
| NZ (1) | NZ231909A (en) |
| PH (1) | PH25854A (en) |
| PL (1) | PL163292B1 (en) |
| PT (1) | PT92650B (en) |
| YU (1) | YU47075B (en) |
| ZA (1) | ZA899879B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3939376C1 (en) * | 1989-11-29 | 1991-05-08 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg, 5450 Neuwied, De | |
| DE4342893C2 (en) * | 1993-12-16 | 1999-09-23 | Lohmann Gmbh & Co Kg | Reversible adhesive, residue-free removable pressure sensitive adhesive, process for its production and use as re-adhesive pressure sensitive adhesive articles |
| EP1239846A2 (en) * | 1999-12-16 | 2002-09-18 | Dermatrends, Inc. | Transdermal administration of phenylpropanolamine |
| US6602912B2 (en) | 2000-06-30 | 2003-08-05 | Dermatrends, Inc. | Transdermal administration of phenylpropanolamine |
| US6673363B2 (en) | 1999-12-16 | 2004-01-06 | Dermatrends, Inc. | Transdermal and topical administration of local anesthetic agents using basic enhancers |
| US6719997B2 (en) | 2000-06-30 | 2004-04-13 | Dermatrends, Inc. | Transdermal administration of pharmacologically active amines using hydroxide-releasing agents as permeation enhancers |
| KR100956865B1 (en) * | 2009-08-10 | 2010-05-11 | 주식회사 라이트론 | Slide pressure packing type linear lighting apparatus |
| EP3532037A4 (en) * | 2016-10-31 | 2020-10-21 | The Corporation Of Mercer University | Transdermal delivery of phenethylamine monoamine releasers |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4291015A (en) * | 1979-08-14 | 1981-09-22 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing a vasodilator |
| JPS57116011A (en) * | 1981-01-08 | 1982-07-19 | Nitto Electric Ind Co Ltd | Pharmaceutical preparation |
| EP0156080B2 (en) * | 1984-03-05 | 1993-10-20 | Nitto Denko Corporation | Percutaneous absorption type adhesive pharmaceutical preparation |
| JPS60185713A (en) * | 1984-03-05 | 1985-09-21 | Nitto Electric Ind Co Ltd | Percutaneous preparation and its production |
| US4692462A (en) * | 1985-03-18 | 1987-09-08 | Menley & James Laboratories, Ltd. | Compositions and method of controlling transdermal penetration of topical and systemic agents |
| DE3629304A1 (en) * | 1986-08-28 | 1988-03-24 | Lohmann Gmbh & Co Kg | TRANSDERMAL THERAPEUTIC SYSTEM, ITS USE AND METHOD FOR THE PRODUCTION THEREOF |
| DE3743945A1 (en) * | 1987-09-01 | 1989-03-09 | Lohmann Gmbh & Co Kg | DEVICE FOR DELIVERING SUBSTANCES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
-
1988
- 1988-12-22 DE DE3843237A patent/DE3843237A1/en active Granted
-
1989
- 1989-12-13 IL IL9267889A patent/IL92678A/en not_active IP Right Cessation
- 1989-12-14 MY MYPI89001760A patent/MY105074A/en unknown
- 1989-12-14 DE DE8989123091T patent/DE58905320D1/en not_active Expired - Fee Related
- 1989-12-14 EP EP89123091A patent/EP0374725B1/en not_active Expired - Lifetime
- 1989-12-14 AT AT89123091T patent/ATE93147T1/en not_active IP Right Cessation
- 1989-12-14 ES ES89123091T patent/ES2045369T3/en not_active Expired - Lifetime
- 1989-12-18 AU AU46843/89A patent/AU614208B2/en not_active Ceased
- 1989-12-19 IE IE407789A patent/IE63878B1/en not_active IP Right Cessation
- 1989-12-19 CS CS897193A patent/CS275356B2/en unknown
- 1989-12-19 YU YU240589A patent/YU47075B/en unknown
- 1989-12-19 FI FI896097A patent/FI95772C/en not_active IP Right Cessation
- 1989-12-20 NZ NZ231909A patent/NZ231909A/en unknown
- 1989-12-20 DK DK651089A patent/DK651089A/en not_active Application Discontinuation
- 1989-12-20 PH PH39752A patent/PH25854A/en unknown
- 1989-12-21 PT PT92650A patent/PT92650B/en not_active IP Right Cessation
- 1989-12-21 DD DD89336084A patent/DD290581A5/en not_active IP Right Cessation
- 1989-12-21 CA CA002006425A patent/CA2006425C/en not_active Expired - Fee Related
- 1989-12-21 NO NO895173A patent/NO178784C/en unknown
- 1989-12-21 ZA ZA899879A patent/ZA899879B/en unknown
- 1989-12-21 HU HU896721A patent/HU203280B/en not_active IP Right Cessation
- 1989-12-22 PL PL89282948A patent/PL163292B1/en unknown
- 1989-12-22 KR KR1019890019229A patent/KR950015055B1/en not_active IP Right Cessation
- 1989-12-22 JP JP1331442A patent/JP2602108B2/en not_active Expired - Lifetime
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| EEER | Examination request | ||
| MKLA | Lapsed |