KR100602434B1 - A patch for the transdermal administration of drugs containing a plurality of unit compartments - Google Patents

Abstract

The present invention is a patch for transdermal administration of a drug comprising a plurality of unit compartments, each unit compartment is a backing layer impermeable to the drug to be included in the patch; An adhesive first matrix layer, the first adhesive layer having one surface in contact with the backing layer and the other surface in contact with the porous membrane layer; A porous membrane layer permeable to a medicament to be contained in each of the unit compartments, one surface of which is in contact with the first matrix layer and the other surface of which is in contact with the second matrix layer; An adhesive second matrix layer, wherein one surface of the second matrix layer is in contact with the porous membrane layer and the other surface is in contact with the protective layer; And a removable protective layer on the adhesive second matrix layer, wherein the first matrix layer and the second matrix layer comprise a drug, wherein each compartment is separated by a drug impermeable wall layer. It provides a patch for transdermal administration of the drug.

Patches, blocks, combination drugs

Description

Patch for the transdermal administration of drugs containing a plurality of unit compartments

1 is a diagram showing a transdermal patch of the present invention in which eight long hexahedral sections are formed.

Fig. 2 is a diagram showing a transdermal administration patch of the present invention in which 64 hexahedral sections are formed.

The present invention relates to a patch for transdermal administration of a drug.

Conventional patches have been used for administering medications through skin absorption. Such a patch has the advantage that the agent can be administered directly into the bloodstream without passing through the digestive tract. In addition, there is an advantage that can be administered without the help of a specialist. The use of a patch for the administration of the drug can also adjust the release and absorption of the drug at a constant rate, deliver high concentrations of the drug directly to the lesion, and avoid the loss of the drug applied to the skin by contact. do.

Known patches generally consist of a backing layer, a layer comprising a medicament and a protective layer. The backing layer is mainly used to support the layer containing the medicament. The layer containing the medicament includes a sack type in which the medicament is contained in a closed space such as a constant sack and a matrix type in which the medicament is contained in the adhesive matrix. U. S. Patent No. 3,797, 494 discloses a patch consisting of a backing layer, a drug storage layer, a microporous membrane layer and a contact adhesive layer. In addition, a method for producing a medical patch is disclosed in, for example, US Pat. Nos. 3,598,122, 3,742,951, 3,996,934 and 4,031,894. The contents of these references are incorporated herein by reference in their entirety.

Conventionally known patches are intended for the administration of a single agent, and cannot be used to administer a combination agent. In order to administer two or more drugs through the skin by using a patch, two or more types of separate patches must be prepared, and these have to be attached to the skin separately. In particular, when the pharmacological characteristics of the drug are very different, when two or more drugs are mixed with each other, the absorption or the efficacy of the drug may be changed by the drug interaction. Thus, there is still a need for a transdermal patch for the drug that can be administered simultaneously to skin lesions while maintaining the two or more drugs as described above while not being mixed with each other during administration.

Accordingly, the present inventors came to complete the present invention while studying a method for administering two or more drugs through the skin using a single patch.

 It is an object of the present invention to provide a patch for transdermal administration of a drug capable of administering a plurality of drugs while keeping them from mixing with each other during drug administration.

The present invention is a patch for transdermal administration of a drug comprising a plurality of unit compartments, each unit compartment is a backing layer impermeable to the drug to be included in the patch; An adhesive first matrix layer, the first adhesive layer having one surface in contact with the backing layer and the other surface in contact with the porous membrane layer; A porous membrane layer permeable to a medicament to be contained in each of the unit compartments, one surface of which is in contact with the first matrix layer and the other surface of which is in contact with the second matrix layer; An adhesive second matrix layer, wherein one surface of the second matrix layer is in contact with the porous membrane layer and the other surface is in contact with the protective layer; And a removable protective layer on the adhesive second matrix layer, wherein the first matrix layer and the second matrix layer comprise a drug, wherein each compartment is separated by a drug impermeable wall layer. It provides a patch for transdermal administration of the drug.

In the patch of the present invention, the wall layer may be one that can be separated by applying a tension. Preferably, the wall layer is formed of a perforation (perforation) is to be separated by the tension. Another example of the wall layer may be that the interface of each compartment is heat sealed.

In the patch of the present invention, the first matrix layer and the second matrix layer of each compartment may be one containing the same or different drugs. Preferably, two or more drugs may be included in each of the other compartments. In this way, drugs that cannot be contained and administered in the same liquid due to differences in stability, optimal solution conditions, and the like to heat, pH, and light of the drug may be included in one of the patches and thus be administered in one of the patches. Can be.

Various backing materials can be used in the patch of the present invention. Suitable backing materials include cellophane, cellulose acetate, ethylcellulose, plasticized vinylacetate-vinylchloride copolymers, polyethylene terephthalate, nylon, polyethylene, polypropylene, polyvinylidenechloride, paper, cloth and aluminum foil. Preferably, flexible occlusion backings are used to suit body shape and to facilitate administration of the drug to the skin.

The adhesive first matrix and the second matrix material may use any dermatologically known pressure-sensitive adhesive material. Suitable matrix materials include acrylic or methacrylic resins such as esters of acrylic acid or methacrylic acid and polymers of alcohols. The alcohols include butanol, pentanol, isopentanol, 2-methyl butanol, 3-methyl pentanol, 2-ethylbutanol, isooctanol, decanol, or dodecanol. In addition to the homopolymer, the polymer may be acrylic acid, methacrylic acid, acrylamide, methacrylamide, N-alkoxymethylacrylamide, N-alkoxymethyl methacrylamide, Nt-butylacrylamide, itaconic acid, vinyl acetate, Copolymers with ethylenically unsaturated monomers such as N-branched alkyl maleamic acid glycol diacrylates, or mixtures thereof. Other suitable matrix materials include natural or synthetic rubbers such as styrenebutadiene, butylether, neoprene, polyisobutylene, polybutadiene and polyisoprene, polyvinylacetate, ureaformaldehyde resins, phenolformaldehyde resins, lysosinol forms Cellulose derivatives such as aldehyde resins, ethyl cellulose, methyl cellulose, nitrocellulose, cellulose acetate butyrate, and carboxymethyl cellulose, and natural gums such as guar, acacia, pectin, starch, dextrin, albumin, gelatin, casein and the like. These adhesive materials can include adhesives and stabilizers as are well known in the art.

Porous membranes used in the present invention are well known in the art and may not be the rate step or rate step of drug release. These porous materials may be homogeneous or heterogeneous in structure throughout the material. Porous materials may include, but are not limited to, for example, having a pore size of 5% to 95% and an effective pore size of about 10 mm 3 to about 100 microns. Porous materials that can be used in the present invention can include polycarbonates, polyamides, modacryl copolymers, polysulfones, halogenated polymers, polychloroethers, acetal polymers and acrylic polymers. Polyurethanes, polyimides, polybenzimidazoles, polyvinyl acetates, and the like may also be included, but are not limited to these examples.

The adhesive matrix layer is covered with a protective film or foil, such as waxed paper, to prevent the drug from being lost from the exposed surface of the pressure sensitive adhesive matrix layer before use.

Patches of the invention can be used to administer a medicament systemically or locally. Preferably, the patch of the present invention can be effectively used to administer a high concentration of the complex agent to a local lesion. The patch of the present invention can be used to administer a high concentration of the complex agent to local lesions of diseases such as, for example, degenerative osteoarthritis and shingles. In this way, the lesion can be locally formed, and a remarkable effect of preventing the drug from being administered systemically can be exerted on a disease in which the drug needs to be administered only to the local lesion. However, the use of the patch of the present invention is not limited to the case where it is used for local lesions, and the systemic administration of the complex agent for the treatment of diseases requiring systemic administration of the agent, for example, chronic pain and cancer pain. Of course it can also be used.

The agent included in the patch of the present invention is, for example, a medicament for treating degenerative osteoarthritis from the group consisting of NSAIDs, alpha2 adrenergic agonists, opioids, NMDA antagonists, GABA agonists, non-opioid central action anesthetics and anti-inflammatory agents. The combination may be selected. Specifically, NSAIDs and alpha2 adrenergic agents, NSAIDs and opioids, NSAIDs, opioids and alpha2 adrenergic agents, NMDA antagonists, alpha2 adrenergic agents and NSAIDs may be included, respectively. For viral diseases with pain and skin lesions, such as shingles or herpes, antiviral agents and anesthetics (eg opioids, local anesthetics, capsaicin) may be included. Moreover, for cancerous or chronic pain, for example, opioids and opioid antagonists may be included. The above NSAIDs include acetaminophen, aceclofenac, celecoxib, choline magnesium trisalicylate, diclofenac sodium, etodolak, phenopropene, ibuprofen, indomethacin, ketoprofen, ketoro Lac, tromethamine, Ronazolac calcium, Meloxycham, Naproxen, Pyroxycam, Rofecoxib, Salsalate, Sulindak, and Tenoshicam. Such alpha2 adrenergic agonists include clonidine, tizanidine, medemidine, padolmidine and brimonidine. Opioids include morphine, codeine, fentanyl, alfentanil, sufentanil, remifentanil, hydromorphine, oxymorphine, hydrocodone, levorfanol, methadone, meperidine, buprenorphine, buttorpanol, pentazocin and nalbuphine Included. NMDA antagonists include ketamine, and dextromethorphan. GABA agonists include midazolam, diazepam, lorzepam and baclofen. Steroids include prednisolone, dexamethasone, triamcinolone, betamethasone, diflucortolone, monomethasone, methylprednisolone, hydrocortisone, clobetasol, aclomethasone, clomethasone, and fluorocinolone. Non-opioid central action anesthetics include tramadol, and antiviral agents include acyclovir, famciclovir, valacyclovir, and the like. Local anesthetics include tetracaine, lidocaine, mepivacaine, bupivacaine, ropivacaine, levo-bupivacaine and the like. Opioid antagonists include naloxone and naltrexone. However, any one that can be separated from each other that can be used in the patch for transdermal administration of the present invention is included, but is not limited to these examples.

Preferably, the patch for transdermal administration of the present invention includes lidocaine, which is a local anesthetic, and acyclovir, which is an antiviral, in the first matrix layer and the second matrix layer. Acyclovir (2-amino-1,9-dihydro-9-[(2-hydroxyethoxy) methyl] -6-purin-6-one) (molecular weight 225.2) is a white or gray crystalline powder, partitioned The coefficient (logP (o / w)) is -1.6, the maximum solubility is 2.5 mg / ml at 37 ° C, and the pKa is 2.27 to 9.25. Lidocaine (2-diethylamino 2 ', 6-acetylided hydrochloride) (molecular weight 234.34) is an amide based local anesthetic, partition coefficient (logP (o / w)) is 2.44, lipid solubility 4.0 mg / ml Plasma protein binding is 74% at pH 8.5 and 61% at pH 7.5. Conventionally, these agents have different properties and cannot be mixed with each other. However, it can be usefully administered through the transdermal patch of the present invention, and synergistic therapeutic effects can be obtained by administering these two agents simultaneously.

In the present invention, each compartment may have any shape, for example, rectangular, circular, oval, and hexahedral. In addition, the number of compartments included in each patch is not particularly limited and may vary depending on the disease and symptoms to be treated.

Hereinafter, an example of the present invention will be described in detail with reference to the accompanying drawings.

1 is a diagram showing a transdermal patch of the present invention in which eight long hexahedral sections are formed. In FIG. 1, each compartment 30 is formed by sequentially stacking a backing layer 12, a first matrix layer 14, a porous membrane layer 16, a second matrix layer, and a protective layer 20. Each compartment 30 may include the same medication or different medications. In use, the protective layer 20 is peeled off and is used by attaching the second matrix layer 18 to a body part, for example, the skin. The drug is administered into the body through the skin from the second matrix layer 18. The medicament lost from the second matrix layer 18 by administration of the medicament is replenished from the first matrix layer 14 through the porous membrane layer 16 at a constant rate. In particular, when different compartments are included in each of the compartments 30, it is possible to administer a variety of agents through a patch through the percutaneous. The compartment 30 of the present invention is separated by a wall layer 22. The wall material is preferably a material which is impermeable to the medicament and can be cut by tension. More preferably, perforation is formed. In this case, the patch can be used by cutting to the desired shape or size.

Fig. 2 is a diagram showing a transdermal administration patch of the present invention in which 64 hexahedral sections are formed. FIG. 2 is identical to the patch of FIG. 1 except for the difference in number and size of compartments. By reducing the size of the compartment 30, the patch of the present embodiment can be used by cutting a patch suitable for shape and size even for finer lesions, and various drugs can be used in combination as desired.

Therefore, since a complex drug can be administered to a disease having a local lesion, for example, a degenerative osteoarthritis and a local lesion of herpes zoster, side effects caused by systemic administration of the drug can be reduced.

According to the patch for transdermal administration of the drug of the present invention, two or more combination drugs can be administered through one patch.

In addition, the patch of the present invention can be used by cutting to the desired shape or size, it is possible to efficiently administer the complex drug to the local lesion. Therefore, by administering the complex drug at a high concentration to the local lesion, side effects due to systemic administration of the drug can be prevented because it is not necessary to administer the compound drug systemically.

In addition, according to the patch of the present invention, it is possible to control the rate at which the drug is administered through the porous membrane layer.

Claims (5)

A patch for transdermal administration of a drug comprising a plurality of unit compartments, each unit compartment comprising: a backing layer impermeable to a medicament to be included in the patch; An adhesive first matrix layer, the first adhesive layer having one surface in contact with the backing layer and the other surface in contact with the porous membrane layer; A porous membrane layer permeable to a medicament to be contained in each of the unit compartments, one surface of which is in contact with the first matrix layer and the other surface of which is in contact with the second matrix layer; An adhesive second matrix layer, wherein one surface of the second matrix layer is in contact with the porous membrane layer and the other surface is in contact with the protective layer; And A removable protective layer on said adhesive second matrix layer, wherein said first matrix layer and said second matrix layer comprise a drug, each compartment being separated by a drug impermeable wall layer Patch for transdermal administration of phosphorus drug. The patch for transdermal administration of a drug according to claim 1, wherein the wall layer can be separated by applying tension. The patch for transdermal administration of a drug according to claim 1, wherein the wall layer is perforation formed so that it can be separated by tension. The patch for transdermal administration of a drug according to claim 1, wherein the first matrix layer and the second matrix layer of each compartment each contain the same or different drugs. 5. The patch for transdermal administration of a drug according to claim 4, wherein each compartment contains a different drug, wherein said drug is lidocaine and acyclovir.

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