JPH09268123A - Cataplasm for local anesthesia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject cataplasm capable of being used as a local anesthesia preparation in the fields of dermatology, dentistry and surgery, excellent in the skin permeability of a medicine, and capable of giving an anesthetic effect in a short time, after the cataplasm is adhered to skin. SOLUTION: This cataplasm is produced by forming a medicine-holding layer on a support. The medicine-holding layer is produced by compounding an adhesive gel base material consisting essentially of a water-soluble polymer, water and a humectant with a local anesthetic agent. One or more compounds selected from polyoxyethylenelauryl ether and 1,3-butylene glycol are added to the subject cataplasm as percutaneous absorption-stimulating agents.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a patch for local anesthesia, more specifically, a transdermal absorption in which a drug-retaining layer formed by mixing a local anesthetic with an adhesive gel base is formed on a support. The present invention relates to a patch for local anesthesia, which is a type of patch and has excellent skin permeability of the drug and can obtain an anesthetic effect in a short time after application. The patch for local anesthesia of the present invention can be used, for example, for reducing pain after surgery or during puncture, and for surface anesthesia before surgery in dermatology and dental fields.

[0002]

2. Description of the Related Art In recent years, in surgery in the dermatology and dental fields,
Lidocaine injection has been widely used for local anesthesia. However, the injection itself causes great pain in the injection itself, and attention is especially required for infants and the elderly.
In addition, for pain after surgery, trauma, and tooth extraction, an analgesic is being actively administered to improve patient compliance. Against this background, as an alternative to conventional injections, many proposals have been made for ointments, patches, etc. containing local anesthetics,
It is also commercially available. For example, Japanese Patent Publication No. 6-18787 proposes an ointment for local anesthesia containing a glycyrrhizin compound as an accelerator. However, in general, ointments
It is difficult to control the dosage, the applied ointment stains clothes, etc., it takes time to remove the ointment during treatment to clean the site, the solvent in the formulation volatilizes and the drug crystallizes, There are problems such as reduced transdermal absorbability.

A patch for local anesthesia has been proposed as a solution to the above problems of ointment. For example,
(1) Japanese Patent Application Laid-Open No. 1-299215 discloses a self-adhesive matrix (rubber-based adhesive) containing a local anesthetic in an amount of 5 to 1
A patch-type medical device having a dispersion of 5% by weight has been proposed. However, rubber-based adhesives generally
It is sensitive to water, and peeling and floating of the patch when sweating poses a problem. (2) JP-A-4-208229 and JP-A-6-208229
-145051 proposes a patch containing an acrylic adhesive containing a local anesthetic. However, the acrylic pressure-sensitive adhesive generally has a poor drug release property, and it takes a long time to achieve the effect. In the patches described in these publications, the local anesthetic is contained in the acrylic pressure-sensitive adhesive base in a proportion of 40 to 65% by weight in order to enhance the drug release property. The higher the value, the lower the adhesive strength.

(3) In Japanese Patent Laid-Open No. 4-305523, a sticky gel base containing a water-soluble polymer substance, water, and a water retention agent as essential components, and 1 to 1 of lidocaine or a salt thereof.
There has been proposed a lidocaine-containing external patch in which a drug holding layer containing 0% by weight is provided on a support. However, in the components and drug contents described in the publication,
It is difficult to obtain a sufficient anesthetic effect, and it is particularly difficult to achieve a local anesthetic effect in a short time. As described above, conventionally, it is easy to use for the purpose of pain relief,
There is a demand for a patch for local anesthesia that is surely effective, but the current situation is that a satisfactory patch has not yet been obtained.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is a patch containing a local anesthetic, which has a short time of onset of a pain relieving effect, a reliable effect can be obtained, and has less skin irritation. To provide. The present inventors, as a result of diligent study to overcome the problems of the conventional technology,
When a drug is mixed with an aqueous adhesive gel base, the drug has excellent skin transferability, and when a specific compound is added as a transdermal absorption enhancer, the drug's skin permeability is significantly improved. It has been found that the water-based and tacky gel bases have low irritation to the skin and have practically sufficient skin adhesion. The patch for local anesthesia of the present invention can obtain the maximum effect when the drug content is 15 to 35% by weight. In addition, when the drug-containing base is applied to a flexible support, it can be surely fitted to a flexion site on the skin surface, and a clinically sufficient local anesthetic effect can be obtained. The present invention has been completed based on these findings.

[0006]

Thus, according to the present invention, there is provided a drug-retaining layer comprising a tacky gel base containing a water-soluble polymer, water, and a humectant as essential components and a local anesthetic. A patch for local anesthesia formed on a support, comprising as a percutaneous absorption enhancer, at least one compound selected from the group consisting of polyoxyethylene uralyl ether and 1,3-butylene glycol. A patch for local anesthesia is provided.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The patch of the present invention comprises a water-based adhesive gel base mixed with a local anesthetic and, as a transdermal absorption enhancer, polyoxyethylene lauryl ether and / or 1,3- A formulation in which butylene glycol is added and the drug content is preferably 15 to 35% by weight is applied on a support, and an anesthetic effect appears in a shorter time than conventional products, and there is no skin irritation. There is little discomfort inside. The adhesive gel base used in the present invention is an aqueous adhesive gel base containing a water-soluble polymer, water, and a humectant as essential components. The base may also contain other additives such as fillers, surfactants and preservatives. As the support, a flexible one is usually used.

Examples of the water-soluble polymer include sodium polyacrylate, polyacrylic acid, polyvinyl alcohol, carboxymethyl cellulose, sodium carboxymethyl cellulose, sodium methyl cellulose, methyl cellulose, polyvinyl pyrrolidone, gelatin and the like. These water-soluble polymers can be used alone or in combination of two or more, and further, they can be used after being crosslinked with a crosslinking agent composed of an organic or inorganic compound. The blending ratio of the water-soluble polymer is usually 0.5 to 50% by weight, preferably 5 to 20% by weight, based on the total amount of each component including the drug (based on the total amount). If this blending ratio is too small, it is difficult to form a gel, and if it is too large, it becomes difficult to uniformly dissolve the water-soluble polymer.

The water in the adhesive gel base has the role of dissolving the water-soluble polymer and swelling the stratum corneum of the skin to help the permeation of the drug through the skin. The mixing ratio of water is usually 10 to 70% by weight, preferably 20 to 60% by weight, based on the total amount. If the water content is too small, it will be difficult to form a gel, and if it is too large, the adhesiveness of the drug holding layer to the skin will be poor. A moisturizer (also called a water retention agent) is added in order to keep the amount of water in the adhesive gel base stable.
Examples of the moisturizer include propylene glycol, glycerin, polyethylene glycol, ethylene glycol, diethylene glycol and the like. They are,
Each can be used alone or in combination of two or more. The blending ratio of the moisturizer is based on the total amount,
Usually 10 to 70% by weight, preferably 20 to 60% by weight
It is. If the blending ratio of the moisturizer is small, the water content in the gel base is likely to be released, and if it is too large, the skin may be contaminated when the patch is peeled off.

A percutaneous absorption enhancer is used in order to accelerate or increase the permeation amount of the drug through the skin. In the patch of the present invention, particularly, polyoxyethylene lauryl ether and / or 1,3-butylene glycol have remarkable effects, so these are selectively used. These two types of percutaneous absorption enhancers may be used alone or in combination. The mixing ratio of the percutaneous absorption enhancer is usually 0.5 to 50% by weight, preferably 1 to 25% by weight, based on the total amount. If the blending ratio of the transdermal absorption enhancer is too small, a rapid and sufficient drug permeation amount cannot be obtained, and if it is too large, gel formation may be hindered.

As the local anesthetic used in the patch of the present invention, those generally used can be used, but in particular, lidocaine, procaine and bupivacaine can be released from the adhesive gel base and the skin. It is preferable because it has good permeability. The compounding ratio of the local anesthetic is usually 15 to 35% by weight, preferably 20 to 30% by weight, based on the total amount. If the compounding ratio of the local anesthetic is too small, the drug permeability becomes poor, and it is not possible to obtain a sufficient drug excess amount in a short time, and if it is too large, the drug utilization rate decreases and the physical properties such as gel strength are adversely affected May be given.

The adhesive gel base may be, for example, a filler (eg, kaolin, titanium oxide, zinc oxide, silica, etc.), a preservative (eg, tocopherol acetate, thymol, etc.), and transdermal, if necessary. A surfactant or the like may be added to emulsify the absorption promoter and the like. The support used in the present invention is preferably a flexible one, for example, polyethylene, polypropylene, nylon, ethylene / vinyl acetate copolymer, polyurethane, polyvinyl chloride, polyester, polyvinylidene chloride, polytetrafluoroethylene, etc. A plastic film, a non-woven fabric, a woven fabric, or a composite support thereof formed from the above can be appropriately used. The thickness of the support is usually preferably 500 μm or less.

The thickness of the drug-retaining layer obtained by blending a local anesthetic, a transdermal absorption enhancer, etc. in an adhesive gel base is usually 25.
˜300 μm, preferably 50 to 200 μm. If the thickness of the drug holding layer is too thin, the adhesion to the skin will be problematic, and if it is too thick, the gel may squeeze out and stain the clothes. The patch for local anesthesia of the present invention can be produced by a conventional method. For example, put a moisturizer and a chemical in a mixer, dissolve by stirring under heating (eg, about 50 ° C), and then add sodium polyacrylate, a cross-linking agent, a filler, an accelerator, a surfactant, etc. In addition, mix until a paste is formed. Next, gradually add purified water or an aqueous solution of polyvinyl alcohol or an aqueous solution of polyacrylic acid,
Mix until uniform. A predetermined amount of the thus-prepared gel base containing a drug is coated on a support with a coating machine such as a knife coater. A release liner (eg silicone treated paper) is attached to the coated surface for protection. Of course, the patch of the present invention is not limited to the above-mentioned manufacturing method, and can be manufactured by various modification methods.

[0014]

EXAMPLES The present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to these examples. In the following,
Parts and percentages are by weight unless otherwise specified.

Example 1 The components shown in Table 1 were uniformly mixed in a mixer, and the resulting mixture was spread on a non-woven fabric using a spreading machine so as to have a thickness of 100 μm. , Cover the coated surface with a polyester film, and
It was cut into a predetermined size to give a patch.

[0016]

[Table 1]

Example 2 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 2 was used.

[0018]

[Table 2]

[Example 3] A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 3 was used.

[0020]

[Table 3]

Example 4 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 4 was used.

[0022]

[Table 4]

Example 5 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 5 was used.

[0024]

[Table 5]

[Example 6] A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 6 was used.

[0026]

[Table 6]

Example 7 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 7 was used.

[0028]

[Table 7]

Example 8 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 8 was used.

[0030]

[Table 8]

Example 9 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 9 was used.

[0032]

[Table 9]

[Example 10] A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 10 was used.

[0034]

[Table 10]

Comparative Example 1 A patch was prepared in the same manner as in Example 1 except that the composition shown in Table 11 was used. This patch corresponds to a conventional product using an adhesive gel base.

[0036]

[Table 11]

[Comparative Example 2] Application was carried out in the same manner as in Example 1 except that a drug-retaining layer was formed on a support using a blend containing a rubber adhesive having the composition shown in Table 12 as a base. An agent was prepared.

[0038]

[Table 12]

Comparative Example 3 The procedure of Example 1 was repeated, except that an ethyl acetate solution of the acrylic adhesive-based blend having the composition shown in Table 13 was coated on a support and dried. To prepare a patch.

[0040]

[Table 13]

[Comparative Example 4] A patch was prepared in the same manner as in Example 1 except that a composition having a small mixing ratio of the local anesthetic shown in Table 14 was used.

[0042]

[Table 14]

Skin Permeation Test by Hairless Rats The amount of lidocaine that permeates rat abdominal excised skin was quantified by HPLC using a Franz diffusion cell. The skin extracted from the abdomen of the hairless rat, the stratum corneum side is the donor phase,
The patches of Examples 1, 4, 5 and Comparative Examples 1, 2 and 3 which were adhered to a Franz diffusion cell and punched into a circle having a diameter of 1.5 cm so that the dermis side would be the receptor phase were applied to the stratum corneum side. . Purified water was added to the receptor phase, the receptor liquid was collected with time, and the drug permeation amount was quantified by HPLC.
The results are shown in FIG. From the results of FIG. 1, it is understood that the patch for local anesthesia of the present invention penetrates the skin in a short time. The results similar to those in Examples 1, 4 and 5 were obtained in the other Examples. The patch of Comparative Example 4 had the same result as that of Comparative Example 1. In addition, the patch of each example is
All had little skin irritation during use.

[0044]

The patch for local anesthesia of the present invention contains a local anesthetic in an aqueous adhesive gel base containing a water-soluble polymer, water and a moisturizer, and the skin permeability of the drug is improved. It is a preparation containing a percutaneous absorption enhancer that is effectively enhanced. Since the drug is absorbed from the skin immediately after application, an anesthetic effect can be obtained in a short time. Therefore, the patch for local anesthesia of the present invention can be used as a preparation for local anesthesia in the areas of dermatology, dentistry, and surgery. Moreover, since the patch of the present invention uses an aqueous gel as a base, it causes very little skin irritation at the patch site.

[Brief description of drawings]

FIG. 1 is a graph showing the results of a skin permeation test of a patch for local anesthesia using hairless rats.

Claims (3)

[Claims] 1. A patch for local anesthesia in which a drug-retaining layer formed by blending a local anesthetic with an adhesive gel base containing a water-soluble polymer, water, and a humectant as essential components is formed on a support. 2. A patch for local anesthesia, which comprises blending at least one compound selected from the group consisting of polyoxyethylene lauryl ether and 1,3-butylene glycol as a transdermal absorption enhancer. 2. The patch for local anesthesia according to claim 1, wherein the local anesthetic is at least one selected from the group consisting of lidocaine, procaine and bupivacaine. 3. The patch for local anesthesia according to claim 1, wherein the blending ratio of the local anesthetic is 15 to 35% by weight based on the total amount of the blended components.