JPH0543054Y2 - - Google Patents

Description

[Detailed description of the invention] (a) Industrial application field The present invention relates to a composite patch preparation that allows a transdermal drug to be absorbed into the body through the skin. A drug storage layer consisting of a body and an adhesive layer are provided separately on one side of a piece of release paper, and the support for the drug storage layer is provided so as to be located on the release paper side. When
By bonding the drug-retaining part and the adhesive layer face-to-face, the drug can be effectively administered into the body through the skin after application to the skin without impairing the activity and adhesive properties of the drug until just before administration. This invention relates to a composite patch preparation.

(b) Prior art Transdermal administration of drugs is less troublesome during administration than oral administration, injections, suppositories, etc., is less susceptible to liver metabolism, does not cause gastrointestinal disorders, and has the advantage of slow drug release. It has the advantage of being able to reduce the number of times of administration because it exerts its medicinal effect over a long period of time, and it is expected that more and more kinds of drugs will be administered transdermally in the future.

By the way, regarding adhesive preparations, there have been proposed methods such as kneading a drug and an adhesive, laminating a drug storage layer and an adhesive layer, and forming an adhesive layer around a drug storage layer.

(c) Problems to be solved by the invention However, in the above method, if the drug is unstable in the adhesive, the drug content may decrease due to decomposition of the drug during the storage period from manufacture to administration. There are also restrictions on the drugs that can be used, as they may not be fully effective when administered.

Further, in the above case, since the drug storage layer and the adhesive layer are in contact with each other in advance, the drug migrates and is distributed throughout the adhesive layer due to diffusion, resulting in the same problem as in the above case. In addition, drugs that generally diffuse easily through the adhesive layer tend to be present in high concentrations at the interface between the adhesive layer and the support, and at the interface between the adhesive layer and release paper.
In such cases, a high concentration of the drug comes into contact with the skin immediately after administration, and if the drug itself is irritating, skin irritation such as redness and edema may occur.
There is a problem in terms of safety.

Furthermore, in the case of a drug with low solubility in the adhesive layer, crystallization may occur when kneaded or laminated with the adhesive layer, which may change transdermal absorbability or impair adhesive properties.

Furthermore, the above-mentioned adhesives have problems such as slipping when applied due to their size and difficulty in adhering them to the skin surface.

(d) Means for Solving the Problems As a result of intensive studies to solve the above problems, the inventors of the present invention have developed a drug storage layer consisting of a drug holding part containing a transdermally absorbable drug and a support. If the adhesive layer is separately provided on one side of a piece of release paper, and the drug storage layer is configured such that the support is located on the release paper side, the adhesive layer can be easily applied by simply folding the drug during transdermal administration. It is possible to bond the drug layer and the drug holding part together without shifting, and
Even if the drug is unstable in the adhesive layer, it is possible to create a patch formulation without reducing the content.Also, since the drug storage layer and the adhesive layer are pasted together during use, the drug can be applied sequentially after application. By diffusion, the drug transfers to the adhesive layer and then to the skin, which prevents high-concentration drugs from coming into contact with the skin immediately after administration, avoiding skin irritation. Even drugs with low solubility do not crystallize or impair adhesive properties.
In addition, the inventors discovered that since the adhesive layer is formed over the entire drug storage layer, it has good skin adhesion and does not slip off, leading to the completion of the present invention.

The present invention will be explained in detail below.

That is, in the composite patch preparation of the present invention, a drug storage layer consisting of a drug holding part containing a transdermally absorbable drug and a support, and an adhesive layer are separately provided on one side of a sheet of release paper. The drug storage layer is characterized in that the support is located on the side of the release paper.

That is, examples of the composite patch preparation of the present invention include the following.

A release paper that can be folded in half from the center has a fold line, with a drug storage layer on one side and an adhesive layer on the other. Paste the layers together.

Various forms are available, such as a drug storage layer fitted into a recessed part of an embossed release paper and laminated at the folds.

In the composite patch preparation of the present invention, a single piece of release paper is used, which can be folded in half from the center, and the drug-retaining part and the support are separated from each other on one side by sandwiching the fold line of the release paper. A drug storage layer is formed on the other side, and an adhesive layer is formed on the other side. In this case, if necessary, it is covered with a removable protective sheet for the purpose of protecting the drug storage layer and the adhesive layer.

To use this, simply remove the removable protective sheet, fold it in half along the fold line, attach the drug-retaining part and the adhesive layer facing each other, and apply the adhesive layer to the skin. be.

As described above, in the composite patch preparation of the present invention, the drug storage layer and the adhesive layer are provided separately, and the two are pasted together during use, so that the activity and adhesive properties of the drug are not impaired until the time of administration. Since high concentrations of the drug do not come into contact with the skin immediately after administration, skin irritation is avoided, and after application to the skin surface, the drug can be effectively administered into the body through the skin.

That is, the composite patch preparation of the present invention differs from conventional ones in that the drug storage layer and the adhesive layer have a structure that is separated and independent from each other until immediately before administration.

With this configuration, even drugs that are unstable in the adhesive layer can be made into patch preparations without causing a decrease in their content. Furthermore, since the drug storage layer and the adhesive layer are pasted together during use, the drug sequentially transfers to the skin by diffusion after being pasted. This prevents high-concentration drugs from coming into contact with the skin immediately after administration, thereby avoiding skin irritation. Furthermore, even drugs with low solubility in the adhesive layer do not crystallize or impair adhesive properties. Furthermore, since the adhesive layer is formed over the entire drug storage layer, it has become possible to adhere the drug closely to the skin surface without slipping.

The composite patch preparation of the present invention thus separates the drug storage layer and the adhesive layer, and consists of a release paper that holds them independently.

The drug storage layer is composed of a transdermally absorbable drug holding part and a support supporting the drug holding part.

In other words, the composite patch usually has a drug storage layer on one side and an adhesive layer on the other side, sandwiching a fold line of release paper that can be folded in half from the center. It is folded at a portion and the drug holding part and adhesive are pasted together facing each other.

In the form of this drug reservoir, the portion holding the drug is formed above the support.

The drug-retaining part mentioned here means that it can stably support the drug described below, and if it is formed so that the drug can be continuously transferred from the skin to the body when applied to the skin, it is particularly important to the retention method. Although there are no limitations, examples of methods for holding drugs include a)
A method of incorporating a drug into an aggregate of fibers such as a non-woven fabric or a woven fabric, or a foam; b) A method in which a drug is formed in powder, liquid, paste, or gel form above a support; c) A method in which a drug is formed above a support. Various forms can be used, such as a method in which the drug is formed into a powder, liquid, paste, or gel state and then covered with a membrane from above, and (d) a method in which a drug previously wrapped in a membrane is formed above the support.

By the way, the above-mentioned membrane is not particularly limited as long as it is capable of holding the drug on the support and is made of a material that continuously transfers the drug from the skin to the body when applied to the skin. It's not something you can do.

Suitable materials for such a film include polymeric materials such as polyethylene vinyl acetate, polyvinyl alcohol, soft polyvinyl chloride, soft polyamide, polyolefin, polyacrylic resin, polyurethane resin, and thermosetting or room temperature vulcanizable silicone rubber. However, it is not limited to the above materials.

In addition, the support is not particularly limited as long as it can support the above-mentioned drug-holding portion, and specifically, examples thereof include polyolefins such as polyethylene, polyurethane, polybutadiene, polyisoprene, polyurethane, etc. Vinyl chloride, polytetrafluoroethylene, chlorinated polyethylene,
Polyvinyl alcohol, polyvinylidene chloride, polyamide, polybutene, polyisobutylene, polyvinyl acetate, polyvinyl chloride grafted ethylene-vinyl acetate copolymer, ethylene-vinyl acetate copolymer, vinyl chloride-acrylonitrile copolymer, vinyl chloride Plastic films or sheets such as vinylidene chloride copolymer, vinylidene chloride-acrylonitrile copolymer, acrylic acid ester-acrylonitrile copolymer, foamed films or sheets of these, and metal-deposited products of these films or sheets may be mentioned. In particular, it is desirable to have sufficient flexibility to follow the movement of the skin surface on which it is applied.

On one side of the release paper used in the present invention, a drug storage layer consisting of a drug retention portion and a support, and an adhesive layer are formed. At this time, the release paper of the part of the drug storage layer that contacts the support can be made weakly adhesive in order to fix the drug storage layer. In this case, a release treatment can be applied to the side of the support that contacts the release paper. For the same purpose, the release paper can be embossed to form a recessed portion so that the drug storage layer can be fitted, and the recessed portion can be made weakly adhesive.

This release paper usually has a drug storage layer on one side and an adhesive layer on the other side, sandwiching a fold line of the release paper that can be folded in half from the center. Since the paper is folded and the drug-retaining part and adhesive layer are bonded face to face, the release paper needs to have enough strength to prevent the bond from shifting when folded.

In addition, this release paper is removed after it is folded and the drug-retaining part and adhesive layer are bonded together, so it can be applied to any type of paper, film, or sheet that has been subjected to so-called silicone treatment. Any material that can be removed after the combination is fine. Specifically, if the support has been subjected to release treatment, the drug storage layer is held in the part of the release paper in contact with the support with a rubber-based or acrylic adhesive as a weak adhesive. It is conceivable to apply silicone treatment to the portions that come into contact with the adhesive layer.

As a material having such performance, a material formed of a material such as plastic film, aluminum foil, or paper and subjected to a release treatment may be used.

Furthermore, the drug used in the present invention is not particularly limited as long as it is transdermally absorbable, and includes both local and systemic drugs.

Examples of such drugs include those listed below.

(a) Corticosteroids: such as hydrocortisone, prednisolone, beclomethasone propionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc. (b) Analgesic and anti-inflammatory agents: For example, acetaminophen, mefenamic acid, flufenamic acid, indomethacin, diclofenac, diclofenac sodium, alclofenac, oxyphenbutazone, phenylbutazone, ibuprofen,
flurbiprofen, salicylic acid, methyl salicylate, l-menthol, camphor, sulindac, tolmetin sodium, naproxen, fuenbufuene, etc. (c) Hypnotic sedatives: e.g. phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidol etc. 2) Tranquilizers: e.g. fluphenazine, teolitazine, diazepam, fludiazepam, flunitosepam, haloperidol, chlorpromazine, etc. e) antihypertensive agents: e.g. clonidine, clonidine hydrochloride, pindolol, propranolol, propranolol hydrochloride, bufranolol, indenolol, nifedipine, nivadipine, Antihypertensive diuretics: e.g. hydrothiazide,
Bendrofluna thiazide, cyclobenziazide, etc. Antibiotics: For example, penicillin, tetracycline, oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc. Anesthetics: For example, lidocaine, dibucaine hydrochloride, benzocaine, aminobenzoic acid Antibacterial substances: e.g. benzalkonium hydrochloride,
Nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc. Antifungal substances: e.g. pentamycin, amphotericin B, pyrrolnitrine, clotrimazole, etc. Vitamins: e.g. vitamin A, ergocalciferol, cholecalcin ferols, octothiacin, riboflavin butyrate, etc. Anti-epileptic drugs: e.g. nitrazepam, mepropamate, clonazepam etc. w Coronary vasodilators: e.g. nitroglycerin, nitroglycol, isosorbide dinitrate, erythritol tetranitrate, pentaerythritol tetranitrate Antihistamines: e.g. diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole, etc. Antitussives: e.g. dextromethorphan, dextromethorphan hydrobromide, terbutasone sulfate , efuedrine, efuedrine hydrochloride, salbutamol, salbutamol sulfate, isoproterenolol, isoproterenolol hydrochloride, isoproterenolol sulfate, etc. Sex hormones: For example, progesterone, estradiol, etc. Antidepressants: For example, doxepin, etc. Cerebral circulation improving agents: For example, hydergine, ergot alkaloids, ifenprodil, etc. Antiemetics, antitumor agents: For example, metoclopramide, clevopride, domperidone, scopolamine, scopolamine hydrobromide, 5-fluorouracil, mercaptopurine, etc. Biomedicines: For example, Polypeptides (TRH,
(derivatives of LHRH), prostaglandins, etc. Other: Examples include fentanil, digoxin, desmopressin, dihydroergotamine methanesulfonic acid, dihydroergotamine tartrate, etc. Two or more of these drugs can be used in combination as necessary. .

The drugs used in the present invention are not limited to those mentioned above, but drugs that are unstable in the adhesive layer or drugs that come into contact with the skin at high concentrations may cause skin irritation or Even drugs that cause crystallization or whose adhesive properties are impaired by drug combination can be used, and are particularly effective in such cases.

Further, the adhesive layer is not particularly limited as long as it is a layer formed of an adhesive that adheres to the skin surface and has adhesiveness at room temperature.

Specific examples of such adhesives include acrylic adhesives, silicone rubber adhesives, polyisoprene rubber adhesives, polyisobutylene rubber adhesives, polybutadiene adhesives, and styrene-butadiene (or isoprene). - Rubber adhesives such as styrene block copolymer rubber adhesives, acrylic rubber adhesives, and natural rubber adhesives, as well as polyvinyl alkyl ether, polyvinyl acetate, partially saponified polyvinyl acetate, polyvinyl alcohol, polyvinyl Vinyl polymer substances such as pyrrolidone, cellulose derivatives such as methylcellulose, carboxymethylcellulose, and hydroxypropylcellulose, polysaccharides such as pullulan, dextrin, and agar, polyurethane elastomers,
A polyester elastomer, a water-soluble acrylic polymer such as polyacrylic acid (or a salt thereof), or a carboxyvinyl polymer is blended with a polyhydric alcohol such as glycerin, a crosslinking agent such as triglycidyl isocyanate, and water. A water-containing gel-like material can also be used.

In addition, when using the above adhesive, if there is a risk of adhesive remaining on the skin surface after application due to insufficient cohesive force and contaminating the skin surface, do not impair skin adhesion. It is preferable to subject the adhesive to a moderate degree of chemical crosslinking treatment or physical crosslinking treatment.

In the present invention, in order to protect the exposed surface of the drug storage layer, a removable protective sheet is provided if necessary on the exposed surface of the drug storage layer, and the exposed surface of the adhesive layer is also protected. For this purpose, a removable protective sheet may be provided on the exposed surface of the adhesive layer, if necessary.

(e) Effect The composite patch preparation of the present invention consists of a drug storage layer consisting of a drug-retaining part containing a transdermally absorbable drug and a support, and an adhesive layer, which are separately formed on one side of a piece of release paper. In addition, the support of the drug storage layer is located on the release paper side, and when used, the drug holding part and the adhesive layer are simply folded so that they face each other, and the adhesive is removed. The layer and the drug-retaining part can be pasted together without slipping, and in this way the adhesive layer and the drug-retaining part are completely pasted together and applied to the human body (skin), so when administered to the skin, The activity and adhesive properties of the drug are not impaired, and skin irritation is avoided because high concentrations of the drug do not come into contact with the skin immediately after administration. It has the ability to be effectively administered in vivo. In other words, unlike kneading or lamination, the drug and adhesive remain independent of each other until just before administration, so even drugs that are unstable in the adhesive can be made into a patch without a decrease in content. Furthermore, since the drug storage layer and the adhesive layer are pasted together during use, the drug gradually transfers to the skin by diffusion after being pasted. This prevents high concentrations of the drug from coming into contact with the skin immediately after administration, thereby avoiding irritation. Also,
Even drugs with low solubility in adhesives do not crystallize or impair adhesive properties. Furthermore, since the adhesive layer is formed over the entire drug storage layer, it has become possible to adhere it closely to the skin surface without slipping.

In addition, in the composite patch preparation of the present invention, a single piece of release paper is used, which can be folded in half from the center, and the drug storage layer is placed on one side and the drug storage layer is placed on the other side across the fold line of the release paper. By forming the adhesive layer separately, in addition to the same effect as described above, it has the effect of making handling during use extremely simple and reliable.

(f) Examples Hereinafter, the present invention will be explained in detail based on Examples, but the present invention is not limited thereto.

In Figs. 1 to 8, the composite patch preparation 1 of the present invention comprises a drug reservoir layer 2 containing a transdermally absorbable drug and an adhesive layer 3, which are provided separately.

Hereinafter, the structure in which the drug storage layer 2 and the adhesive layer 3 are provided separately will be described in more detail.

That is, as shown in FIGS. 1a and 1b, the composite patch preparation 1 of the present invention has a release paper 4 that can be folded in half from the center, and the drug is stored on one side across the fold line 4a. Layer 2, adhesive layer 3 on top of the other
is provided separately. In this case, the drug storage layer 2 is composed of a drug holding part 2a and its support body 2b.

In this case, the above-mentioned composite patch preparation 1 usually has a drug storage layer 2 and an adhesive layer 3 separately provided on a single release paper 4, and the fold line 4a provided on the release paper 4 The drug storage layer 2 and the adhesive layer 3 are fixed in advance at a position such that they can be bonded together without shifting when folded. With this configuration, the user can easily bond the drug storage layer 2 and the adhesive layer 3 together by simply bending the release paper 4 along the fold line 4a during use. Furthermore, the ease of operation on the user's side, that is, the ease of pasting together, is advantageous in terms of medication guidance.

In FIG. 1b, a peelable protective sheet 5 is provided on the exposed surfaces of the drug storage layer 2 and adhesive layer 3 in order to protect them.

Further, the drug holding portion 2a described above is shown in FIGS. 2 and 3.
As shown in the figure, a membrane 6 made of a drug-permeable material is formed above the support 2b by covering or wrapping it, and when this composite patch preparation 1 is applied to the skin, the membrane 6 is applied to the skin. The drug may be transferred continuously from the skin into the body.

Alternatively, instead of the above embodiment, as shown in FIGS. 4 to 6, the release paper 4 is embossed to form a recess 4b, and either the drug storage layer 2 or the adhesive layer 3 is placed in the recess 4b. , or a structure that incorporates both may be used.

Furthermore, instead of these, as shown in FIG. 7 and FIG.
The drug storage layer 2 and the adhesive layer 3 are laminated separately so that they do not come into direct contact with each other with a releasable isolation sheet 7 interposed between them, and when used, the isolation sheet 7 is removed and the drug storage layer 3 is separated. 2 and the adhesive layer 3 may be directly bonded together and applied to the human body (skin).

FIGS. 9 and 10 show the state of the composite patch preparation 1 after the drug storage layer 2 and adhesive layer 3 are pasted together and the release paper 4 and isolation sheet 7 are removed when the composite patch preparation 1 is used. Support 2 as shown in FIG.
b. The drug holding part 2a and the adhesive layer 3 do not have to all have the same size; the adhesive layer 2 may be larger than the drug holding part 2a as shown in FIG. 10, and these sizes may vary depending on the formulation. It can be arbitrarily determined according to the purpose and function of the device.

(g) Effect of the invention The composite patch preparation of the invention consists of a drug storage layer consisting of a drug-retaining part containing a transdermally absorbable drug and a support, and an adhesive layer, which are separately placed on one side of a piece of release paper. In addition, the support in the drug storage layer is located on the release paper side, and when used, the drug holding part and the adhesive layer are simply folded so that they face each other. It is possible to bond the layer and the drug-retaining part together without shifting, and since they are bonded together in this way, the activity and adhesive properties of the drug are not impaired until the time of administration, and it is possible to maintain high concentration of the drug immediately after administration. Since the drug does not come into contact with the skin, skin irritation is avoided, and after application to the skin surface, the drug can be effectively administered into the body through the skin.

In addition, in the composite patch preparation of the present invention, since the drug storage layer and the adhesive layer are provided on a single sheet of release paper, this can be folded in half from the center,
By separately forming a drug storage layer on one side and an adhesive layer on the other side across the fold line of the release paper, it has the effect of making handling during use extremely simple and reliable. be.

[Brief explanation of the drawing]

FIG. 1a is a plan view showing one embodiment of the present invention, FIG. 2 is a side view thereof, FIGS. 2 to 8 are side views showing other embodiments, and FIGS. 9 and 10 are It is a sectional view showing the state at the time of use. 1... Composite patch preparation, 2... Drug storage layer, 2a
...Drug holding part, 2b...Support, 3...Adhesive layer, 4...Release paper, 4a...Fold line, 4b...Recess, 5...Protective sheet, 6...Membrane, 7...Isolation sheet.

Claims (1)

[Scope of utility model registration request] A drug storage layer consisting of a drug holding part containing a transdermally absorbable drug and a support, and an adhesive layer are separately provided on one side of a piece of release paper, and the drug storage layer has a drug storage layer consisting of a support and an adhesive layer. A composite patch preparation that is located on the release paper side.