JPS62228009A - Member for external use - Google Patents

Abstract

PURPOSE:A member for external use, obtained by specifying the melting temperature of a thermoplastic base in a given shape containing a drug as an essential ingredient, having shape retaining property in application to the integument and capable of administering in a constant amount, melting and fluidizing by body temperature after application thereto and closely adhering to the integument on the other hand. CONSTITUTION:A member for external use containing (A) a percutaneously absorbable drug or cosmetic in an amount of 0.05-30wt% based on the total thermoplastic base as an essential ingredient and further (B) a percutaneous absorption accelerator in an amount of preferably 0.1-30wt% based on the above-mentioned base containing the drug and (C) a stabilizer in am amount of preferably 0.05-5wt% based on the above-mentioned base containing the drug and formed into a given shape. In the above-mentioned base, the melting temperature thereof is set at 25-45 deg.C. Thereby, since the given shape is retained in application to the integument, the drug and cosmetic can be administered in a constant amount, melted and fluidized by body temperature after application thereto to closely adhere to the application part on the other hand to afford the aimed member for external use having improved adsorbability of the drug in the living body without feeling pain in application.

Description

Detailed Description of the Invention (a) Industrial Application Field The present invention relates to an external member that is fixed to the surface of a living body and melts at the surface temperature and exhibits fluidity. Moreover, the present invention relates to an external member for medical or cosmetic use that has shape retention properties when applied to the surface of a living body or an affected area, and exhibits fluidity at body temperature after being applied to a living body.

(b) Conventional technology External medicines and cosmetics can be classified according to their properties: (1) atomized materials such as sprays, (2) powders, (3) granules, and (4)
) liquid, (5) cream-like material, (6) sheet-like material, etc.

(c) Problems to be solved by the invention These are formed into such properties by taking into account their use and efficacy, as well as convenience and drug stability. There is an incompatibility between α, which is the administration of drugs or cosmetics to living organisms, and (b) suppression of physical irritation at the application site when administering drugs or cosmetics.

In other words, α, which is the administration of a fixed amount of a drug or cosmetic to the surface of a living body, requires a certain shape, and in this sense, if the above properties are not sheet-shaped, the dose will be constant. It is difficult to maintain a constant dosage for creams, powders, liquids, etc.

On the other hand, from the perspective of physical stimulation, administering drugs or cosmetics to affected areas such as wounds or burns often causes severe pain even with the slightest physical action, and depending on the condition of the wound or burn, it may be difficult to administer drugs or cosmetics to affected areas such as wounds or burns. Even administering liquid to the affected area is difficult11
It may become.

As described above, there are no external pharmaceutical preparations or cosmetics that solve the two problems of administering a fixed amount of drugs or cosmetics to the affected area and suppressing physical irritation.

(d) Means for Solving the Problems The inventors of the present invention have conducted intensive studies on an external member that solves the two problems all at once. The present invention has been completed by discovering an external member that achieves the purpose of quantitatively administering drugs and cosmetics, and which melts and fluidizes due to body temperature after being applied to the outer skin and adheres closely to the application site.

In other words, the basic idea for solving the two problems described in Section 2 is to form the external use member into a predetermined shape, thereby making sure that the dose is always constant, and furthermore, placing the external use member gently on the application site such as the affected area. By melting, fluidizing, and spreading at body temperature, drugs and cosmetics previously contained in the external member are administered into the body from the application site.

That is, the present invention provides a thermoplastic group in a predetermined shape containing a drug or a cosmetic as an essential ingredient, wherein the thermoplastic group is characterized in that its melting temperature is set at 25 to 45°C. It is something to do.

The present invention will be explained in detail below.

The drug used in the present invention is not particularly limited as long as it is absorbed transdermally into the body when applied to the skin or affected area.

One specific example is as follows.

b) Corticosteroids: For example, hydrocortiscin, prednisolone, beclomethasone probionate, flumethacin, triamcimerone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide,
fluocinolone ace]nidoacetate, clobetasol propionate, etc.; oral) analgesic anti-inflammatory agents: e.g. acerami77en, mefenamic acid, flufenamic acid, indomethacin, diclo7enac, diclo7enatrinum, alcro7
Enatsuku, Oxy-7 Embutazone, Phenylbutacin,
Ibuprofen, flurbipro-7ene, salicylic acid, methyl salicylate, p-menthol, can-7ar, Slingunk, tolmetin sodium, naproxen, 7-enbu7en, etc. c) Minor sedatives: For example, fumebarbital, amobarbital, cyfrobarbital, triazolam, nitrazepam, lorazebam, peridol, etc.; 2) tranquilizers: such as flu7enanone, theoritazine, diazepam, fludiazepam, fludiazepam, haloperidol, chlorpromanone; and 2) antihypertensive agents: For example, clonidine, clonidine hydrochloride,
Pindolol, Propranolol, Proplav Hydrochloride 0-
Antihypertensive diuretics: For example, hydrothiazide, bendroflunathiazide, cyclobenziazide, etc. ) Antibiotics: e.g. penicillin, tetracycline,
Oxytetra → neuculin, 7-lanomycin sulfate, erythromycin, chloramphenicol, etc.; 1) Anesthetics: e.g. lidocaine, nobucoin hydrochloride, pensicaine, ethyl 7-benzoate, etc.; 1) Antibacterial substances: For example, benzalkonium hydrochloride, nitro7razone, nyscutin, acetosulfamine, clotrimazole, etc. Antifungal substances: for example, pentamycin, amphotericin B, virolnidoline, clotrimazole, etc. Vitamins: for example, vitamin A1 ergocalcin ferol, cholecalciferol, off) f-acin, riboflavin butyrate, etc., p) anti-epileptic drugs: e.g. nitrazepam, mebrobamate, clonazepam, etc., w) coronary vasodilators: e.g. nitroglycerin, nitroglycol, insorbido Nitrate, erythritol tetranitrate 1, pentaerythritol tetranitrate 1, propyl nitrate, etc.) Antihistamines: For example, Noahenhydramine hydrochloride,
chlorpheniramine, nophenylimiguzole, etc.; iv) Antitussives: such as dextromethorphan hydrobromide, terbutasone sulfate, ephedrine, ephedrine hydrochloride, salbutamol sulfate, isoprotenol hydrochloride, isobrotyl sulfate, etc. Hormones: e.g. propsterone, estradiol, etc.) Antigraphs: e.g. doxebin) Cerebral circulation improving agents: e.g. videlgin, nilgott alkaloids, iaenprodil, etc.) Antiemetics, antiulcer agents: e.g. metoclopramide, clevopride, Tonperiton, Scopolamine, Scopolamine Hydrobromide, 5-
fluorouracil, mercaptopurine, etc.) Biomedicine: For example, polypeptides (TRH, l-1
4RH derivatives), prostaglandins, etc.; n) Others: Examples include 7-entanyl, digoxin, desmobrecin, dihydroergotamine methanesulfonic acid, nohydroergotamine tartrate, etc. Two or more of these drugs may be used as necessary. 1 can be used together.

Furthermore, the cosmetics used in the present invention are those applied to the body for the purpose of cosmetics, that is, to cleanse, beautify, increase charm, change appearance, or keep the skin or hair healthy. It is not particularly limited as long as it is.

Specific examples of cosmetics described in item 1 include the following.

(b) Water products, such as lotions, colognes, perfumes, etc., (b) Emulsions, such as creams, milky lotions, etc., (c) Mixtures, such as lotions containing powder components, water white powder, etc., (d) Jelly-like substances. Cosmetics such as creams, packs, etc. (e) Paste-like cosmetics such as foundation, etc. (f) Stick-like cosmetics such as stain-like makeup products, 1) Red, etc. (g) Cake-like cosmetics such as solid white powder, pressed (1) Pencil-type cosmetics, such as eyebrow ink, eyeliner, etc., (1) Aerosol-type cosmetics, such as cologne, perfume, etc., (3) Soap, such as cosmetic bar soap, cream soap, etc. It will be done.

Furthermore, the thermoplastic base material used in the present invention contains the above-mentioned drug or cosmetic as an essential component, and contains 0.05 to 30% by weight of the drug or cosmetic based on the entire base material. be.

The most significant feature of the present invention is that the above-mentioned thermoplastic base material, that is, the mixed composition of the drug or cosmetic described below with the thermoplastic material described below, and further a transdermal absorption promoting agent and a stabilizer added as desired. The point is set so that the melting point of the substance is in the range of 25 to 45°C.

” - As a thermoplastic cable, its melting point is 25 to 45°
It is not necessary that it be in the range C, but the melting point will be in the range of 25 to 45 ° C by mixing with the drugs or cosmetics listed in "-", transdermal absorption promoting aids, stabilizers, etc. described below, and There is no particular limitation as long as it is safe even when applied to the human body.

Specific representative examples of such thermoplastic materials include gelatin, aliphatic higher alcohols with carbon numbers of 14 or more, higher fatty acids, beeswax, carnauba wax, kinderilla wax, spermaceti wax, cetanol, and solids with carbon numbers of 18 or more. type paraffin, ceresin, cerasox, hard lanolin, lanolin alcohol, reduced lanolin, polyoxyethylene lanolin,
Polyoxyethylene sorbicun fatty acid ester, sorbitan monolaurate, polyoxyethylene glycol fatty acid ester, polyoxyethylene alkyl ethyl,
Polyoxyethylene non-glycerin fatty acid ester, sugar ester, etc. are pre-prepared.

Also, -J-, drugs or cosmetics (hereinafter referred to as drugs)
Transdermal absorption promoting aids can be simply defined as those that promote the release of drugs to the body surface, but this also includes the solubility and diffusivity of drugs within the thermoplastic material. Transdermal absorbability, such as those that have the function of improving keratin water retention, keratin softening, keratin permeability (loosening), acting as a penetration aid or pore opening agent, and changing the skin interface condition. Examples include those that have a function of improving the quality of the product, and those that also have the above-mentioned functions.

Examples of aids for promoting transdermal absorption of these drugs include glycols (mainly drug solubility) such as noethylene glycol, propylene glycol, polyethylene glycol, and polypropylene glycol, oils and fats such as olive oil, squalene, and phosphorus. (mainly improving drug diffusivity),
Urea, urea derivatives such as allantoin (mainly water retention properties of the stratum corneum -1-), trimethyldecyl phosphooxide, methyloctyl sulfoxide, dimethyl sulfoxide, trimethylborumamide', trimethylacetamide, trimethyllaurylamide, dodecylpyrrolidone , polar solvents such as isosorbitol (mainly to improve stratum corneum permeability), salicylic acid (
Mainly for keratin softening properties), amino acids (mainly for keratin softening properties), amino acids (mainly for keratin softening properties),
31 ftg Mukai J-,), nicotinic acid benzyl ester (mainly a hand opening agent), sodium lauryl sulfate (
(Mainly changes the interface state of the skin).

In addition, water, plasticizers such as diisopropyl adibate, 7-talic acid ester, diethyl sebacate, hydrocarbons such as liquid paraffin, various emulsifiers, 1-xylated stearyl alcohol, N-methylpyrrolidone, glycerin ester, 1- dodecyl-azacyclohebutan-2-one,
Examples include isopropyl myristate and ethyl laurate. There is one type of these depending on the need, −
It can be added to the amount.

The amount added is 0 to the thermoplastic base material containing drugs.
．． A range of 1 to 30% by weight is desirable.

In addition, -1- stabilizers include benzoic acid and its salts, salicylic acid and its salts, 7-ethyl, sorbic acid and its salts, isopropylmethyl 7-ethyl, and resorcinol, and the amount added It is desirable that the amount of the compound added to the thermoplastic base material containing the drug is in the range of 0.05 to 5% per month.

The drug-containing thermoplastic substrate is formed into a predetermined shape, such as a rectangular plate, a square plate, a triangular plate, a polygonal plate, a disk, etc., in order to always maintain a constant dose of drugs. .

That is, when the external member of the present invention is applied, it is gently placed on the skin or the affected area, and after application, it melts and melts due to body temperature.
It becomes fluidized and spreads over the application surface, and then the drugs are absorbed into the body from the application site.

In this case, this external member may be applied to the skin or affected area and fixed from the outside with an adhesive tape or the like, if desired.

Next, an example of manufacturing the external member of the present invention will be described.

■First, a transdermal absorption promoting agent is added to the thermoplastic material and mixed, which causes the melting point of the mixture of 5= to be approximately 25 to 45 degrees.
J: Set the sea urchin to be C, then add drugs to this mixture and dissolve or disperse it, heat it, melt it, pour it into a mold of a predetermined shape, cool and solidify it, and form it into this predetermined shape. The externally used parts are taken out and packaged. in this case,
It is necessary to set the room temperature lower than the melting point of the obtained external use member so that the shape retention of the external use member is not impaired.

■First, drugs are dissolved or dispersed in a transdermal absorption promoting agent, and a thermoplastic material is gradually added to this mixture until the melting point is -
1-. A thermoplastic base material containing drugs is obtained by adjusting the temperature within the range described in (1).

The thus obtained thermoplastic base material is processed in the same manner as in (2) to obtain the external member of the present invention.

■After filling a predetermined amount of the thermoplastic base material obtained in step (1) or (2) into a bag having a relatively hydrophobic surface made of, for example, a polyethylene sheet, a fluorine sheet, etc., the filling in the bag is performed. Seal the opening.

Next, the bag filled with this thermoplastic base material is heated to the melting point of the thermoplastic base material, and in this state it is compressed between two flat plates through a spacer of an appropriate thickness. After forming into a predetermined shape, it is cooled and solidified.

Thereafter, the flat plate is removed and the case is opened to obtain the external shrine of the present invention formed into a predetermined shape.

When the thus obtained external use member is gently placed on the surface of the skin or the affected area, the external use member melts and becomes fluid due to body temperature and spreads on the surface of the skin or affected area, promoting the absorption of drugs into the body. . In this case, the external member may be fixed with adhesive tape or the like, if desired.

In addition, by placing a single dose of drugs in a flexible film or sheet bag and heating it in a general household, the thermoplastic base material described in 2. After being melted and fluidized, it may be compressed between two flat plates in the same manner as in Section 1.2, placed in a refrigerator to cool and solidify, and then taken out and opened for use. It is.

(c) Effect The external member of the present invention requires a predetermined shape and has a constant size, so it is easy to administer drugs. j is always constant, and since this external member is made of a thermoplastic base material containing a drug that melts and fluidizes with body temperature, when the external member is applied to the skin surface or the affected area, it melts and fluidizes with body temperature. Expanding,
This has the effect of further promoting the absorption of drugs into the living body.

In addition, since the above-mentioned external member melts and becomes fluidized by body temperature, when it is gently applied to a wound or burn, the external member melts, becomes fluidized, and spreads naturally. It has the effect of suppressing pain when applied.

Furthermore, since the Externally Used Shrine described in Section 2 is melted and fluidized by body temperature, it can penetrate into areas where it is applied, even if it has complex irregularities. Moreover, it has the effect of uniformly administering drugs into the body from such a site.

(r) Examples Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

In addition, in the examples, all parts or % mean parts by weight or % by weight.

Example 1 A thermoplastic base material containing a drug (penzalkonium chloride: antibacterial substance) consisting of the following formulation was obtained.

Gelatin 3.0% Glycerin 69.95% Water
27.0% benzalkonium chloride 3 parts of 0.05% gelatin was added to 27 parts of water, the mixture was heated to 60°C and dissolved, and 0.05 part of benzalkonium chloride, an antibacterial substance, was added. , and further mixed with 69.95 parts of glycerin to obtain a liquid thermoplastic base material.

The thermoplastic base material described above becomes a shape-retaining gel, or solidifies, when left at a temperature of 5°C for about 2 hours, but when raised to a temperature of around 30°C, it melts and fluidizes in about 10 minutes, forming a gel-like state. It became.

=16- Example 2 A thermoplastic substrate containing a drug (silver sulfadiazine: antibacterial substance) consisting of the following formulation was obtained in the same manner as in Example 1.

Gelatin 3.0% glycerin
69.5% Water 27.0%
Sur7 Asianon Silver 0.5% Example 3 A thermoplastic substrate containing a drug (neomycin sulfate: antibacterial substance) consisting of the following formulation was obtained in the same manner as in Example 1.

Gelatin 3.0% Glycerin 69.95% Water
27.0% neomycin sulfate 0.05% Example 4 A vitamin-containing thermoplastic base material (facial cosmetic) consisting of the following formulation was obtained.

Gelatin 3.0% Glycerin 69.0% Water 27,0
%L-asfulvic acid magnesium phosphate 1.0% Next, an example of the process using the thermoplastic base material of each of the above examples (1 to manufacture the external member of the present invention) will be explained in detail with reference to FIG. 1. .

The thermoplastic base material (1) of each of the above examples was heated to a temperature of 60°C.
Maintain it in a liquid state near the
1.88 filled in +n square polyethylene bag body (2),
Seal (Step A, Step B).

This thermoplastic base material 0) filled bag body (2) is 280μ thick.
[Two stainless steel plates (size: 15cm) heated to around 60°C through a spacer of
m square) (4) (4) (Step C) and pressurized into a flat shape (Step F)). Next, in this pinched state, the temperature was increased to 5°C.
When it is cooled and solidified until it becomes , the external member (1) of the present invention is obtained inside the bag body (2) (Step IE).

An example of how to use the external member (1) obtained in this way will be explained with reference to FIGS. 2 and 3. - Take out the external member (1) from the bag (2) and apply it to the skin (5). It melts and becomes fluid due to body temperature, and eventually, as shown in Figure @3,
The external member (1) spreads and comes into close contact with the body, thereby allowing the drugs to be absorbed into the body.

(g) Effects of the Invention As a result of the external member of the present invention having the structural acid shown in -, the dosage of drugs can always be kept constant, and the external member can be applied to the skin surface or affected area. It melts and becomes fluidized by body temperature, spreads and adheres closely to the surface to which it is applied, and therefore has the effect of increasing the rate of absorption of drugs into the body.

In addition, when the external member of the present invention is gently applied to an affected area such as a wound or burn, the external member 44 melts, becomes fluid, and naturally spreads, so you do not feel pain when applying it (during administration). It has an effect that can be easily applied to any person.

Furthermore, since the external member of the present invention melts and becomes fluidized by body temperature, it has extremely excellent effects, such as being able to be applied to complex areas.

[Brief explanation of drawings]

Fig. 1 is a process diagram showing an example of manufacturing the external member of the present invention, Fig. 2 is a cross-sectional view of a main part showing an example of application of the external member of the present invention to the skin surface, and Fig. 3 is a process diagram showing the melting and flow of the external member of the present invention. FIG. (1)...Thermoplastic base material, (2)...Bag body, (3)
... Spacer, (4) ... Stainless steel plate, (5).
··Skin. =20-

Claims (1)

[Claims] (1) A thermoplastic base material of a predetermined shape containing a drug or cosmetic as an essential ingredient, the thermoplastic base material having a melting temperature of 2.
An external member characterized in that the temperature is set at 5 to 45°C.