JP2000319187A - Carbon dioxide transcutaneous and transmucosal absorption composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition that permits skin and mucosa to continuously absorb carbon dioxide transcutaneously or transmucosally and is useful for beauty and therapy of skin and mucosa by allowing the objective composition to include water, a thickener and foamed carbon dioxide. SOLUTION: This composition comprises (A) water, (B) a thickener and (C) foamed carbon dioxide. In a preferred embodiment, the contents of the component A and the component B are 60-99.9 wt.% and 0.1-40 wt.% based on the total amounts of the components A and B, respectively. The content of the component C is preferably >=0.1 vol.%, more preferably >=1 vol.% and particularly >=2 vol.%. In addition to the above-stated components, (D) a moisturizing agent, (E) a lipophilic substance, and (F) a surfactant may be used preferably in amounts of 0.1-25 wt.%, 0.01-10 wt.% and 0.01-10 wt.%, respectively.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention
Transmucosal absorption composition, kit for producing the composition, itching associated with mucocutaneous disease or mucosal disorder containing the composition, skin ulcer based on peripheral circulatory disorder, cold sensation, numbness;
The present invention relates to a preventive or therapeutic agent and cosmetic for any disease selected from the group consisting of dental disease, skin mucosal damage, purulent skin disease, dyskeratosis, musculoskeletal disease and nervous system disease.

[0002]

2. Description of the Related Art For the treatment of itch, topical antihistamines and antiallergic agents are generally used as topical treatments. They are used when itching occurs and temporarily reduce it to some extent. For non-steroidal anti-inflammatory drugs and steroids, itching is generally used to treat itching caused by eczema. These drugs are intended to prevent inflammation by suppressing inflammation.

[0003] However, topical antihistamines and antiallergic agents have little effect on atopic dermatitis, athlete's foot or insect itch. Topical non-steroidal anti-inflammatory drugs and steroids have a weak effect on itch and do not have immediate effect. Also, steroids are not easy to use because of strong side effects.

[0004] Carbon dioxide is known to improve blood circulation, and a poultice containing carbon dioxide has been proposed (Japanese Patent Application Laid-Open No. 62-286922). However, JP 6
The poultice disclosed in Japanese Patent Application Laid-Open No. 2-286922 dissolves carbon dioxide generated using a carbonate and an organic acid in water and uses the dissolved carbon dioxide as dissolved carbon dioxide. The absolute amount of carbon dioxide dissolved in water is extremely small. Therefore, no substantial effect can be expected.

Japanese Patent Application Laid-Open No. 61-207322 discloses an effervescent solid composition containing ascorbic acid and a carbonate, each of which is coated, wherein the composition contains ascorbic acid and a carbonate by the time of use. It is stabilized so as not to generate carbon dioxide upon reaction. Its use is as described in the upper left column of page 4 of the publication and foods such as effervescent powdered drinks and tablets, and effervescent It is used as a cleaning agent for bath salts, contact lenses, toilets, bathtubs, etc., and there is no technical problem of retaining generated carbon dioxide gas.

JP-A-3-227910 discloses a method for producing a foamy aqueous solution having a softening effect on the cuticle of the nail, and it is described that the foaminess makes the product comfortable and comfortable. Nothing is said about the action of carbon dioxide. Further, as an acid component for generating carbon dioxide, pyrrolidone carboxylic acid whose salt complements the softening action of urea is used, and no other acid is disclosed. Further, none of the solutions obtained in Examples 1 to 5 has sufficient viscosity to retain the generated carbon dioxide gas, and the generated carbon dioxide gas rapidly diffuses into the air.

[0007] Japanese Patent Application Laid-Open No. 4-31521 discloses a mousse-like lubricant for lubricating during intercourse and for preventing vaginal dryness. The lubricant contains polyacrylamide, glycerin, vitamin E and carbon dioxide, which are high molecular coagulants. The mousse-like lubricant uses carbon dioxide to increase the volume when removed from the container. The mousse-like lubricant discharged from the container quickly loses carbon dioxide, and at the time of application to the genitals, the carbon dioxide has almost completely disappeared. In addition, it is necessary to apply a very thin coating for lubricating applications, and cannot retain carbon dioxide gas.

JP-A-5-501421 is a solid pharmaceutical composition containing a water-insoluble or microencapsulated drug together with an acid, a carbonate, a thickening agent or a suspending agent, wherein the composition comprises water. Is to suspend the drug. As described in the lower left column to the lower right column on page 4 of the publication, the addition of an acidic substance and a base to the formulation promotes the hydration of the thickener, but is carried out in such an amount that foaming does not occur, It has to be noted that the thickener-coated granules tend to remain floating due to the bubbling of carbon dioxide, which slows the dissolution of this substance and produces the opposite effect to the desired effect. That is, Japanese Patent Publication No. 5-501421 discloses a solid pharmaceutical composition having an acid and a carbonate,
When the composition is dissolved in water, foaming by carbon dioxide does not substantially occur.

An object of the present invention is to provide athlete's foot, insect bites, atopic dermatitis, monetary eczema, xerosis, seborrheic eczema, urticaria, prurigo, housewife eczema, acne vulgaris, impetigo, Folliculitis,
Accompanied by cutaneous mucosal diseases or mucosal disorders such as carbohydrates, sclerosum, cellulitis, pyoderma, psoriasis, ichthyosis, palmar keratosis, lichen, pityriasis, wounds, burns, cracks, erosions, and frost acne It is to provide a composition effective for itching.

[0010] The present invention also provides a method for treating a mucous membrane injuries such as pressure sores, wounds, burns, stomatitis, stomatitis, skin ulcers, cracks, erosions, erythema and gangrene; Dental diseases such as inflammation, alveolar pyorrhea, denture ulcer, melanized gingiva, stomatitis; skin ulcers due to peripheral circulation disorders such as obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory dysfunction, and varicose veins Or cold, numbness; rheumatoid arthritis,
Musculoskeletal diseases such as neck-shoulder-arm syndrome, muscle pain, arthralgia, lumbago; nervous system diseases such as neuralgia, polyneuritis, and Smon's disease; psoriasis, chicken eyes, octopus, ichthyosis, palmoplantar keratosis, moss Dyskeratosis such as psoriasis and pityriasis; acne vulgaris, impetigo, folliculitis,
Purulent skin diseases such as bunches, cough, cellulitis, pyoderma, purulent eczema; suppression of recurring hair after hair removal (waste hair treatment); freckles, rough skin, dull skin, firmness and luster of skin A composition for carbon dioxide transdermal and transmucosal absorption, which is effective for cosmetic problems such as skin and hair such as loss of luster and loss of gloss of hair, and partial obesity,
An object of the present invention is to provide a kit for producing the composition.

[0011]

Means for Solving the Problems Item 1. A composition containing water, a thickener and foamed carbon dioxide, and capable of continuously absorbing carbon dioxide through the skin and transmucosally. Item 2. Water 60-99. Based on the total amount of water and thickener.
Item 4. The composition according to Item 1, comprising 9% by weight and 0.1 to 40% by weight of a thickener. Item 3. Item 3. The composition according to Item 1 or 2, further comprising a humectant. Item 4. Item 3 wherein the content of the humectant is 0.1 to 25% by weight.
A composition according to claim 1. Item 5. Item 5. The composition according to any one of Items 1 to 4, further comprising a lipophilic substance. Item 6. Item 6. The composition according to Item 5, wherein the content of the lipophilic substance is 0.01 to 10% by weight. Item 7. Item 7. The composition according to any one of Items 1 to 6, further comprising a surfactant. Item 8. Item 8. The composition according to Item 7, wherein the content of the surfactant is 0.01 to 10% by weight. Item 9. 0.1% by volume or more, preferably 1% by volume or more, more preferably 2% by volume or more, still more preferably 3% by volume or more, particularly preferably 4% by volume or more, most preferably 5% by volume or more of cellular carbon dioxide Item 10. The composition according to any one of Items 1 to 8 including: Item 10. 40% by volume or more, preferably 60% by volume or more, more preferably 80% by volume or more of the foamed carbon dioxide held in the composition is foamed for 5 minutes or more, preferably 30 minutes or more, more preferably 1% or more. More than an hour, especially 2
Item 10. The composition according to any one of Items 1 to 9, which can be maintained for not less than an hour. Item 11. On the edge of a glass plate with a smooth surface of 40 cm in length, 1 g of it was applied in the form of a disk with a diameter of 1 cm, and after standing at an angle of 60 degrees with respect to a horizontal plane so that the disk came on, 5 seconds later The moving distance of the disk is within 30 cm, preferably within 25 cm, more preferably within 20 cm, especially 1 cm.
Item 11. The composition according to any one of Items 1 to 10, which is within 5 cm. Item 12. From a basic composition containing water, a thickener and a carbonate, and a carbon dioxide generation auxiliary (I) containing at least 10% or more of an acid with respect to the number of moles of the carbonate contained in the basic composition. In use, the carbon dioxide generated in the composition obtained by mixing these at the time of use is retained, and 40% of the carbon dioxide retained in the composition at the maximum volume after foaming.
Volume% or more, preferably 60 volume% or more, more preferably 80 volume% or more in a bubble form for 5 minutes or more, preferably 3% or more.
A kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide, which can be held for 0 minute or more, more preferably 1 hour or more, especially 2 hours or more. Item 13. The basic composition contains 60 to 99.8% by weight of water and 0.1 to 0.1% by weight of the total amount of water, thickener and carbonate.
Item 1 containing 30% by weight and 0.1 to 10% by weight of carbonate
2. The kit according to 2. Item 14. Basic composition and carbon dioxide generation auxiliary (I)
Is increased by 0.1% by volume or more, preferably 1% by volume or more, more preferably 3% by volume or more, particularly preferably 5% by volume or more of the total volume of the basic composition and the carbon dioxide generation auxiliary. Item 14. The kit according to Item 12 or 13, which is at least 7% by volume, most preferably at least 7% by volume. Item 15. Item 15. The kit according to any one of Items 12 to 14, wherein the basic composition contains 0.1 to 25% by weight of the humectant. Item 16. Item 16. The kit according to any one of Items 12 to 15, wherein the basic composition contains 0.01 to 10% by weight of a surfactant. Item 17. Item 17. The kit according to any one of Items 12 to 16, wherein the basic composition contains 0.01 to 10% by weight of a lipophilic substance. Item 18. On the edge of a glass plate with a smooth surface of 40 cm in length, 1 g of it was applied in the form of a disk with a diameter of 1 cm, and after standing at an angle of 60 degrees with respect to a horizontal plane so that the disk came on, 5 seconds later The moving distance of the disk is within 30 cm, preferably within 25 cm, more preferably within 20 cm, especially 1 cm.
Item 18. A composition produced from the kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide according to any one of Items 12 to 17, which is within 5 cm. Item 19. An acidic composition containing water, a thickener and an acid,
At least 1 based on the number of moles of the acid contained in the acidic composition
Carbon dioxide generation aid containing 0% or more carbonate (I
I), containing carbon dioxide generated in a composition obtained by mixing them at the time of use, and 40% by volume of carbon dioxide held in the composition at the maximum volume after foaming.
Or more, preferably 60% by volume or more, more preferably 80% by volume or more.
A kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide, which can hold a volume% or more in a bubble form for 5 minutes or more, preferably 30 minutes or more, more preferably 1 hour or more, especially 2 hours or more. Item 20. Item wherein the acidic composition contains 60 to 99.8% by weight of water, 0.1 to 30% by weight of a thickener, and 0.1 to 10% by weight of an acid based on the total amount of water, a thickener and an acid. 20. The kit according to 19. Item 21. The volume increase rate when the acidic composition and the carbon dioxide generation auxiliary (II) are mixed is 0.1% by volume or more, preferably 1% by volume of the total volume of the acidic composition and the carbon dioxide generation auxiliary (II). Item 21. The kit according to item 19 or 20, wherein the content is at least 3% by volume, particularly preferably at least 5% by volume, most preferably at least 7% by volume. Item 22. Item 22. The kit according to any one of Items 19 to 21, wherein the acidic composition contains 0.1 to 25% by weight of a humectant. Item 23. Item 23. The kit according to any one of Items 19 to 22, wherein the acidic composition contains 0.01 to 10% by weight of a surfactant. Item 24. Item 24. The kit according to any one of Items 19 to 23, wherein the acidic composition contains 0.01 to 10% by weight of the lipophilic substance. Item 25. On the edge of a glass plate with a smooth surface of 40 cm in length, 1 g of it was applied in the form of a disk with a diameter of 1 cm, and after standing at an angle of 60 degrees with respect to a horizontal plane so that the disk came on, 5 seconds later The composition has a disc moving distance of 30 cm or less, preferably 25 cm or less, more preferably 20 cm or less.
Item 21. A composition produced from a kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide according to any one of Items 19 to 24, which is within 15 cm in particular. Item 26. The composition according to any one of Items 1 to 11, or the composition according to Item 18 or 25, itching associated with mucocutaneous mucosal disease or mucosal disorder; cutaneous ulcer due to peripheral circulatory disturbance, cold sensation, numbness; dental disease A prophylactic or therapeutic agent for any disease selected from the group consisting of: skin mucosal damage; purulent skin disease; dyskeratosis; musculoskeletal disease; and nervous system disease. Item 27. Item 1. The composition according to any one of Items 1 to 11, or Item 1.
8 or 25 compositions that reduce or obscure spots and freckles, whitening action, skin rejuvenation action, skin firming action, face, legs, arms, abdomen, flank, back, neck, chin, etc. A cosmetic having any of an action of improving partial obesity, an action of improving skin quality, and an action of suppressing recurrent hair after hair removal. Item 28. 28. The cosmetic according to claim 27, wherein the cosmetic is a cream, a pack, a gel, a paste, or a mask. Item 29. Carbon dioxide transdermal containing carbonate, acid, thickener, and water in a state that does not substantially generate carbon dioxide, and containing bubble-like carbon dioxide by mixing carbonate, acid, thickener, and water -A kit of any of the following (i) to (iv) from which a composition for transmucosal absorption can be obtained: (i) a basic composition containing water, a thickener and a carbonate, water, and thickening A kit comprising an acidic composition containing an agent and an acid. (ii) A kit comprising a carbonate and a solid acid (granules, granules, powder), and a viscous composition comprising water and a thickener. (iii) A kit comprising a viscous composition comprising water and a thickener, and a composite granule (fine granules, powder) of a carbonate and an acid. (iv) A kit containing a carbonate, an acid, a thickener, and water.

Mucocutaneous diseases or disorders accompanied by itching include athlete's foot, insect bites, atopic dermatitis,
Eczema, xerosis, seborrheic eczema, hives, prurigo, housewife eczema, acne vulgaris, impetigo, folliculitis, bunches, swelling, cellulitis, pyoderma, psoriasis, ichthyosis And palmoplantar keratosis, lichen, pityriasis, wounds, burns, cracks, erosions, and frost acne.

[0013] The skin mucous membrane damage includes pressure sores, wounds, burns, stomatitis, stomatitis, skin ulcers, cracks, erosions, frost acne,
Necrosis and the like.

The purulent skin diseases include acne vulgaris, impetigo, folliculitis, bunches, cough, cellulitis, pyoderma, purulent eczema, and the like.

As dyskeratosis, psoriasis, chicken eyes, octopus,
Ichthyosis, palmoplantar keratosis, lichen, pityriasis and the like.

Examples of the musculoskeletal diseases include rheumatoid arthritis, cervico-shoulder-arm syndrome, muscle pain, joint pain, and low back pain.

The dental diseases include gingivitis, alveolar pyorrhea, denture ulcer, blackened gingiva, stomatitis and the like.

Examples of peripheral circulatory disorders that cause skin ulcers, cold sensation, and numbness include obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory disorder, and varicose veins.

The nervous system diseases include neuralgia, polyneuritis, Smon's disease and the like.

[0020]

DETAILED DESCRIPTION OF THE INVENTION The compositions of the present invention, whether normal or abnormal due to any disease or injury,
It is applied to skin, mucous membrane tissue, subcutaneous tissue, etc. having a vascular system. The skin includes all outer skins including palms, soles, and scalp. Mucosal tissues include nasal mucosa, oral mucosa, periodontal mucosa, lip mucosa, external genital mucosa, perianal mucosa, and the like. Subcutaneous tissue includes fascia, subcutaneous fat, dermis and the like.

Carbon dioxide does not disappear in a short time, for example, within a few seconds to several minutes as in carbonated beverages and effervescent preparations, but is kept in a bubble state in the composition of the present invention and is continuously released. .

In the present invention, "a composition capable of continuously absorbing carbon dioxide transdermally and transmucosally" means, in a preferred embodiment, carbon dioxide of 5 minutes or more, preferably 20 minutes or more, more preferably Means a composition capable of transdermally and transmucosally absorbing carbon dioxide for 30 minutes or more, more preferably 1 hour or more, particularly preferably 1.5 hours or more, and most preferably 2 hours or more.

In the present invention, “bubble carbon dioxide” means, for example, when carbon dioxide is generated by reacting a carbonate with an acid or when carbon dioxide is blown from a carbon dioxide cylinder into the composition. It means carbon dioxide contained as air bubbles, and the air bubbles may be made of only carbon dioxide, or may contain air together with carbon dioxide.
The proportion of carbon dioxide in the "bubble carbon dioxide" is 30% by volume or more, preferably 50% by volume or more, more preferably 70% by volume or more, particularly preferably 90% by volume or more, and most preferably 100% by volume.

In the kit of the present invention, the carbon dioxide generation auxiliary (I) may consist only of an acid, and together with the acid, water, a thickener, a binder, a disintegrant, an excipient, and a surfactant , A humectant, a lipophilic substance, a pH adjuster, and the like. The carbon dioxide generation auxiliary (I) is used in an amount of at least 10 to the number of moles of the carbonate contained in the basic composition.
%, Preferably about 10 to 300%, more preferably 5%
Contains about 0-200% acid.

In the kit of the present invention, the carbon dioxide generation auxiliary (II) may consist only of a carbonate, and together with the carbonate, water, a thickener, a binder, a disintegrant, an excipient,
Surfactants, humectants, lipophilic substances, pH adjusters and the like may be included. The carbon dioxide generation auxiliary (II) contains at least 10%, preferably about 10 to 300%, more preferably about 50 to 200% of a carbonate based on the number of moles of the carbonate contained in the acidic composition. .

Since the composition of the present invention is intended for continuous transdermal and transmucosal absorption of carbon dioxide, when the composition is applied to a target site, the composition contains more foamy carbon dioxide. Preferably, the composition is applied thickly so as to completely cover the target site with the composition. In the case of a composition having low fluidity, the composition may be absorbed by an absorbent material such as gauze or a nonwoven fabric to have a thickness at the time of application of the composition. The thickness to apply depends on the target disease and purpose,
It is at least 0.2 mm, preferably at least 0.5 mm, more preferably at least 1.0 mm, further preferably at least 1.5 mm, most preferably at least 2.0 mm. However, if the thickness is too large, application of the composition becomes difficult. Therefore, the thickness of the composition to be applied or the absorber impregnated with the composition is 5
cm or less, more preferably 4 cm or less, still more preferably 2 cm or less, and most preferably 1 cm or less.

The compositions of the present invention may be applied to a wide range of skin or mucosal tissues, eg, for use in foot care applications including treatment of athlete's foot itch by dipping the entire foot in the compositions of the present invention. Alternatively, if a calf, a lower leg, or the like is immersed in the composition of the present invention, a partial skin effect at a desired site can be obtained, and the skin can be partially thinned.

Further, in the case of a whole-body burn or a partial burn, the burn can be treated by immersing the burn portion entirely in the composition of the present invention. Similarly, by applying the composition of the present invention to the whole body, the whole body can be cared for.

When the composition of the present invention is used for the treatment or prevention of mucocutaneous diseases or mucosal disorders, or for cosmetic purposes on skin or mucous membranes, the composition can be applied directly to the site of use, Alternatively, an absorbent material such as a gauze or a sponge may be impregnated, or these materials may be formed into a bag, the composition may be put into the bag, and attached to a use site. Even higher effects can be expected by using a combination therapy that covers the site where the composition is applied or adhered with a film or a dressing material with poor air permeability. It is also effective to immerse the desired site in a container filled with the composition. In that case, if the composition is supplemented with carbon dioxide using a carbon dioxide cylinder or the like, the effect is maintained more.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention can be used without losing its effectiveness for a long period of time by storing it in a closed container or the like. It is also possible to use it by preparing it before use. In preparation for use, since the composition for transdermal / transmucosal absorption of carbon dioxide becomes cold due to the endothermic reaction accompanying the generation of carbon dioxide, the material for preparation is appropriately warmed to a temperature near body temperature by microwave oven or hot water bath. The composition may be warmed or warmed after preparation.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is preferably used at pH 5 to 8 for damaged tissues and mucous membranes. When the pH of the composition is 5 or less, pain is caused by stimulation of an acid, and when the pH is 8 or more, tissue may be damaged due to protein denaturing action by alkali. The composition of the present invention is preferably used at pH 3 to pH 9 for undamaged skin. If the pH of the composition is less than 3, side effects such as pain and rash may be caused by skin irritation of the acid, and if the pH is more than 9, the tissue may be damaged due to the protein denaturing action of alkali.

The production of the composition of the present invention is preferably carried out in an atmosphere of carbon dioxide under normal pressure or pressure to increase the ratio of carbon dioxide in the foamed carbon dioxide.

A surfactant may be added to the composition of the present invention in order to efficiently contain bubbles of carbon dioxide in the composition. Examples of the surfactant include the following. Nonionic surfactants: diglycerol dioleate, sorbitan fatty acid ester, glycerin monooleate, glyceryl monostearate, propylene glycol monostearate, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene・ Polyoxypropylene block polymer, polyoxyethylene hydrogenated castor oil ester, etc.・ Cationic surfactants: stearyltrimethylammonium chloride, cetylmethylammonium chloride, stearyldimethylbenzylammonium chloride, myristylbenzylammonium chloride, benzalkonium chloride, acylglutamate, DL-2-Pyrroli
done-5-Carboxylic Acid Salt of Ethyl N-Cocoyl-L-Ar
ginate etc. Anionic surfactant: acyl N-methyltaurine salt,
Alkyl ether phosphate, sodium alkyl sulfate, N-acyl amino acid salt, higher fatty acid soap, polyoxyethylene alkyl ether sulfate and the like. -Amphoteric surfactants: alkyl dimethyl amino acetate betaine, alkyl amide dimethyl amino acetate betaine, 2-
Alkyl-N-carboxy-N-hydroxyimidazolinium betaine and the like. -Nonionic surfactants: polyoxyethylene lauryl ether, propylene glycol fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxy Propylene alkyl ether, ethylene oxide / propylene oxide block copolymer, etc. -Natural surfactants: lecithin, lanolin, cholesterol, saponin and the like.

The amount of the surfactant is 0.01 to 1 with respect to the total amount of water, the thickener and the surfactant or the total amount of the composition.
0% by weight, preferably 0.05 to 7% by weight, more preferably 0.01 to 5% by weight, most preferably 0.1 to 2% by weight.

The surfactant is used not only in a composition containing carbon dioxide in a bubble form from the beginning, but also in a basic composition even in the case of a kit for preparing a carbon dioxide transdermal / transmucosal absorption composition prepared at the time of use. Alternatively, if the acidic composition contains a surfactant, the foaming property is improved, and the content of the foamed carbon dioxide is preferably increased.

As the thickener of the composition of the present invention, one or more selected from the group consisting of natural polymers, semi-synthetic polymers, synthetic polymers and inorganic substances can be used. The amount of the thickener used is 0.1 to 40% by weight of the composition of the present invention.
Preferably, the content is 1 to 15% by weight, more preferably 3 to 10% by weight.

The plant-based polymer among the natural polymers used as the thickener in the present invention includes gum arabic, carrageenan, galactan, agar, quince seed, guar gum, tragacanth gum, pectin, mannan, locust bean gum,
Wheat starch, rice starch, corn starch, potato starch and the like.

Microbial polymers among the natural polymers used for the thickener in the present invention include curdlan, xanthan gum and the like.
Succinoglucan, dextran, hyaluronic acid, pullulan and the like.

The protein-based polymer among the natural polymers used for the thickener in the present invention includes albumin, casein, collagen, gelatin, fibroin and the like.

The cellulosic polymer among the semi-synthetic polymers used as the thickener in the present invention includes ethyl cellulose, carboxymethyl cellulose and its salts, carboxymethyl ethyl cellulose and its salts, carboxymethyl starch and its salts, croscarmellose and Its salts, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate,
Powdered cellulose, methylcellulose, methylhydroxypropylcellulose and the like can be mentioned.

The starch-based polymer in the semi-synthetic polymer used as the thickener in the present invention includes pregelatinized starch, partially pregelatinized starch, carboxymethyl starch, dextrin, methyl starch and the like.

Alginate polymers among the semi-synthetic polymers used for the thickener in the present invention include sodium alginate,
Alginic acid propylene glycol ester and the like.

Other polysaccharide polymers among the semi-synthetic polymers used for the thickener in the present invention include sodium chondroitin sulfate and sodium hyaluronate.

The synthetic polymer used as the thickener in the present invention includes carboxyvinyl polymer, sodium polyacrylate, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol, polyvinylpyrrolidone, methacrylic acid-ethyl acrylate copolymer, methacrylic acid- Ethyl methacrylate copolymer, ethyl methacrylate / methacrylic acid trimethylammonium ethyl copolymer, dimethylaminoethyl methacrylate / methyl methacrylate copolymer, and the like.

Inorganic substances used for the thickener in the present invention include hydrous silicon dioxide, light anhydrous silicic acid, colloidal alumina, bentonite, laponite and the like.

Water is contained in the composition of the present invention in an amount of about 60 to 99.9% by weight, preferably about 75 to 99% by weight, more preferably about 85 to 97% by weight.

As a method for containing and retaining cellular carbon dioxide in the composition of the present invention, there is a method in which carbon dioxide is directly blown into a composition containing water and a thickener using a carbon dioxide gas cylinder or the like.

The present invention can be carried out by reacting a substance which generates carbon dioxide by a reaction in a composition containing water and a thickener to generate carbon dioxide, or by mixing the components of the kit of the present invention. Carbon dioxide can be contained and retained in the composition.

The carbonate used in the present invention is not particularly limited as long as it reacts with an acid to generate carbon dioxide, but is preferably ammonium carbonate, ammonium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, or potassium sesquicarbonate. , Sodium carbonate, sodium bicarbonate, sodium sesquicarbonate, lithium carbonate, lithium bicarbonate, lithium sesquicarbonate, cesium carbonate, cesium bicarbonate,
Alkali metal or alkaline earth metal carbonate, hydrogen carbonate, sesquicarbonate, basic carbonate such as cesium carbonate, magnesium carbonate, magnesium hydrogen carbonate, calcium hydrogen carbonate, calcium carbonate, magnesium carbonate hydroxide, barium carbonate And one or two of these
More than one species is used.

The acid used in the present invention may be either an organic acid or an inorganic acid, and one or more of these may be used.

Examples of the organic acid include linear fatty acids such as formic acid, acetic acid, propionic acid, butyric acid and valeric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid,
Fumaric acid, maleic acid, phthalic acid, isophthalic acid, dicarboxylic acids such as terephthalic acid, glutamic acid, acidic amino acids such as aspartic acid, glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, α-oxybutyric acid, Oxy acids such as glyceric acid, tartronic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid, and gluconic acid.

Examples of the inorganic acid include phosphoric acid, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sodium sulfite, potassium sulfite, sodium pyrosulfite, potassium pyrosulfite, sodium acid hexametaphosphate, potassium acid hexametaphosphate, and acid pyrophosphate. Sodium, potassium acid pyrophosphate, sulfamic acid and the like.

The composition of the present invention can be used as
Skin quality improvement, freckle improvement, skin rejuvenation, skin tightening,
It has effects such as partial thinning, suppression of recurring hair after hair removal, and improvement of hair gloss, and can be used in the form of creams, gels, pastes, packs, masks, and the like. In addition, fragrances and coloring materials can be added,
Flavors include natural flavors, synthetic flavors, compounded flavors and the like.

As an additive that can be added to the pack, 0.1 to 20% by weight of ethanol or the like can be added as a volatile alcohol to add a refreshing feeling at the time of the pack. 0.1 to 15% by weight of saccharides such as polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and sorbitol, and mucopolysaccharides such as sodium chondroitin sulfate for moisturizing the skin. As a humectant.
1 to 25% by weight can be blended. For the purpose of softening the skin, fats and oils such as olive oil, macadamia nut oil, jojoba oil, liquid paraffin, squalane, octyldodecyl oleate, etc. can be blended in an amount of 0.01 to 10% by weight. Vitamin C and its derivatives, whitening agents such as arbutin, kojic acid, etc. for the purpose of enhancing whitening, skin whitening, skin rejuvenation, etc.
1 to 15% by weight, and 0.01 to 20% by weight of a cell activator such as pantothenyl ethyl ether and placenta extract. 0.01 to 10% by weight of an anti-inflammatory agent such as allantoin or glycyrrhizin salt, 0.1 to 20% by weight of a bactericide such as chlorhexidine or acrinol, and 0.1 or 0.1% by weight of a preservative such as methylparaben or 1,2-pentanediol. -25% by weight may be added. For the purpose of preventing separation of oils and fats, 0.01 to 10% by weight of a surfactant such as polyxyethylene nonylphenyl ether and sorbitan monostearate can be blended.

As a component that can be blended with the cream, the cream is mainly composed of an oil phase component, an aqueous phase component, and a surfactant.
Hydrocarbons such as petrolatum, liquid paraffin, ceresin, microcrystalline wax, olive oil, macadamia nut oil, almond oil, jojoba oil, avocado oil, hardened palm oil, castor oil, evening primrose oil, oils such as synthetic triglycerides, oleic acid, stearic acid, Fatty acids such as isostearic acid, myristic acid, palmitic acid and behenic acid, waxes such as beeswax, lanolin, carnauba wax, candelilla wax, cetanol, stearyl alcohol, behenyl alcohol, octyldodecyl alcohol, higher alcohols such as cholesterol, glycerin triesters, Pentaerythritol tetraester,
0.0 synthetic ester such as cholesteryl ester
1 to 10% by weight can be blended. Glycerin, propylene glycol, polyethylene glycol,
0.1 to 25% by weight of a humectant such as 1,3-butylene glycol, diglycerin, dipropylene glycol, sorbitol, mannitol, and 0.1 of a mucus such as quince seed, pectin, xanthan gum, sodium alginate, and carboxyvinyl polymer. ~ 40% by weight,
Alcohols such as ethanol and isopropanol are added to 0.
1 to 20% by weight can be blended. Surfactants include nonionic surfactants such as glycerin monostearate, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, and polyoxyethylene alkyl ether, and anionic surfactants such as fatty acid soap and sodium alkyl sulfate. 0.01 to 10% by weight. Flavors and pigments can also be blended without any particular limitations in the amounts that are used in ordinary cosmetics. 0.1 to 10% by weight of antioxidants such as vitamin E and dibutylhydroxytoluene; 0.01 to 15% by weight of whitening agents such as vitamin C and its derivatives, arbutin and kojic acid; pantothenyl ethyl ether and placenta extract 0.01 to 15% by weight of a cell activator, such as 0.01 to 10% by weight of an anti-inflammatory agent such as allantoin or glycyrrhizin salt, 0.1 to 20% by weight of a bactericide such as chlorhexidine or acrinol, methyl paraben or 1%. 0.1 to 25% by weight of a preservative such as 2,2-pentanediol.

In the composition of the present invention, in addition to the components or raw materials described above, a humectant such as ceramide, fermented rice extract, wine or wine extract, marigold extract, etc. is contained in an amount of 0.1 to 25% by weight. 0.1 g of fat metabolism promoter such as caffeine, kola extract, and algo extract
0.1 to 10% by weight, 0.1 to 10% by weight of exfoliating components such as fruit acid, sulfur, salicylic acid and resorcinol, β-
Anti-inflammatory agents such as glycyrrhetinic acid, glycyrrhizic acid derivatives, allantoin, azulene, ε-aminocaproic acid, hinokitiol, hydrocortisone;
0% by weight, 0.1-10% by weight of astringents such as zinc oxide, zinc sulfate, allantoin hydroxyaluminum, aluminum chloride, aluminum sulfate, zinc sulfocarbonate, tannic acid, citric acid and lactic acid, and cooling such as menthol and camphor 0.1 to 10% by weight of vitamin A,
Vitamins such as vitamin B group, vitamin D, vitamin E, calcium pantothenate, ethyl pantothenate, and biotin are used in amounts of 0.01 to 10% by weight, and hormones such as estradiol, estrone, ethinyl estradiol, cortisone, prednisone, and prednisolone. 0.01 to 5% by weight, 0.01 to 10% by weight of an antihistamine such as diphenhydramine hydrochloride, chlorpheniramine maleate, and glycyrrhizic acid derivative, and plant properties such as aloe extract, chamomile extract, licorice extract, oak extract and loquat extract 0.01 to 10% by weight of anti-inflammatory and cell-activating substances, 0.01 to 5% by weight of antipruritic agents such as camphor and menthol, Amyris, Ylang-ylang, Elemi, Kajupte, Guayakwood, Clary Sage, Clove, Co Iba, coriander, Cypress,
Sandalwood, Santoxilam, Cedarwood, Citronella, Cinnamon, Jasmine, Star Anise, Spike Clavender, Spearmint, Sage, Geranium Rose, Tea Tree, Dill, Niauli, Neroli, Pine, Basil, Patchouli, Palmarosa, Fur, Fennel, Petit Glen, Frankincense No herbal essence used for aromatherapy such as, French marigold, peppermint, bergamot, benzoin, marjoram, myrtle, mandarin, myrrh, lime, lavandin, lavender, litzer, lemon, lemongrass, rose, rosewood, eucalyptus, etc. .
It can be added in an amount of from 0.01 to 5% by weight. In addition to the examples shown here,
The components usually blended in cosmetics can be blended in the composition of the present invention without any particular limitation.

The basic composition or the acidic composition of the kit for producing the composition for transdermal and transmucosal absorption of carbon dioxide and the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention contains all the components necessary for production. It can be manufactured by simply mixing and stirring in one container at the same time.However, when the thickener is a solid such as powder, in order to make it easy to use and expand easily, the thickener must be a liquid humectant It is preferable that the other components are dissolved or dispersed gradually, and the mixture is slowly mixed and stirred. The amount of the humectant may be selected so as to have fluidity enough to flow out when the container containing the liquid mixture with the thickener is tilted. Wt%, preferably 80-400 wt%, more preferably 100-300 wt%, even more preferably 120-250 wt%, most preferably 130 wt%.
~ 200% by weight. Glycerin as a humectant,
1,3-butylene glycol, propylene glycol,
Examples include polyethylene glycol, dipropylene glycol, diglycerin and the like.

The amount of the humectant is about 0.1 to 25% by weight, preferably about 1 to 20% by weight, more preferably about 3 to 15% by weight, based on the total amount of the composition.
When the composition of the present invention particularly comprises water, a thickener, a humectant and carbon dioxide, water 60 to 60% by weight of the whole composition.
Preferred are 99.8% by weight, 0.1-20% by weight of thickener and 0.1-20% by weight of humectant.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention can be obtained by simply mixing and stirring the raw materials by replacing the air in the container with carbon dioxide in a closed stirring mixer such as a vacuum emulsifier. However, by adding a surfactant to the raw material, a large amount of cellular carbon dioxide can be contained and held in a short time. The content of the surfactant in the composition is 10% by weight or less, preferably 0.1% by weight or less.
It is from 0.1 to 7% by weight, more preferably from 0.1 to 5% by weight, most preferably from 0.5 to 3% by weight.

The basic or acidic composition of the composition for transdermal and transmucosal absorption of carbon dioxide and the kit for producing the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention can be prepared by adding a lipophilic substance to the skin. The composition can be easily removed from the skin and mucous membranes without impairing the effects such as the effect and the effect of promoting wound healing. As the lipophilic substance, any of natural fats, semi-synthetic fats and synthetic fats can be used without any limitation. The content of the lipophilic substance in the composition is 0.01 to 10% by weight, more preferably 0.3 to 5% by weight, and most preferably 0.5 to 3% by weight.

The lipophilic substances include oils and fats such as avocado oil, almond oil, olive oil, cocoa butter, hardened palm oil, synthetic triglyceride, evening primrose oil, castor oil, sunflower oil, jojoba oil, macadamia nut oil, squalane,
Ceresin, solid paraffin, microcrystalline wax, liquid paraffin, hydrocarbons such as petrolatum, carnauba wax, candelilla wax, wax such as beeswax and lanolin, isostearyl alcohol, 2-octyldodecanol, stearyl alcohol, cetanol, cholesterol, hexadecyl Alcohol, higher alcohols such as behenyl alcohol, fatty acids such as isostearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, myristic acid, isopropyl myristate, 2-
Synthetic esters such as cetyl ethylhexanoate, glycerin triester, cholesteryl ester, pentaerythritol tetraester, and diisostearyl malate;
Examples include silicone oils such as cyclomethicone, dimethylpolysiloxane, methylpolysiloxane, and methylphenylpolysiloxane.

The composition of the present invention can be used in a tube or a wide-mouthed container. The container is preferably of a completely sealed type so that the foamed carbon dioxide contained in the composition of the present invention does not decrease or disappear. The material of the container is plastic such as nylon PA, polyethylene, polypropylene, polystyrene, AS resin, ABS resin, polyethylene terephthalate, polyvinyl chloride, ethylene-vinyl alcohol copolymer resin, polyacetal, aluminum, iron, brass, etc., depending on the shape of the container. Metals such as stainless steel, glass such as soda-lime glass, potassium lead glass, and milky glass can be appropriately selected and used. The basic composition or acidic composition of the kit of the present invention can be used in a tube or a wide-mouthed container, but in the case of a tube, it is put into an empty wide-mouthed container and mixed with a carbon dioxide generation auxiliary. In the case of a wide-mouthed container, a container having a rounded bottom is preferable because it can be easily mixed and stirred with a carbon dioxide generation auxiliary. In the case of a wide-mouthed container, the volume of the composition produced from the kit of the present invention is larger than the sum of the basic composition or the acidic composition and the carbon dioxide generation auxiliary, so that the volume of the composition is 1. A container having a capacity of 5 times or more, preferably 1.6 times or more, more preferably 1.7 times or more, and most preferably 1.8 times or more is used. The material of the container is alkali-resistant in the case of a basic composition, and any acid-resistant material in the case of an acidic composition can be used without any limitation, but nylon PA, polyethylene, polypropylene,
Plastics such as polystyrene, AS resin, ABS resin, polyethylene terephthalate, polyvinyl chloride, ethylene-vinyl alcohol copolymer resin, and polyacetal, and metals such as aluminum, iron, brass, and stainless steel are appropriately used depending on the shape of the container. In the case of an acidic composition, glass such as soda-lime glass, potassium lead glass, and milky glass can be used. The mixing and stirring of the basic composition or the acidic composition and the carbon dioxide generation aid can be performed by hand, but if a butter knife or a spatula is used, the mixing and coating can be performed.

[0063]

EFFECTS OF THE INVENTION The composition of the present invention comprises athlete's foot, insect bites, atopic dermatitis, monetary eczema, xerosis, seborrheic eczema, urticaria, prurigo, housewife eczema, acne vulgaris, pus Crusts, folliculitis,
Accompanied by cutaneous mucosal diseases or mucosal disorders such as carbohydrates, sclerosum, cellulitis, pyoderma, psoriasis, ichthyosis, palmar keratosis, lichen, pityriasis, wounds, burns, cracks, erosions, and frost acne itch;
Pressure sores, wounds, burns, stomatitis, skin ulcers, cracks, erosions,
Cutaneous mucosal damage such as erythema and gangrene; graft engraftment, incomplete engraftment of flaps, etc .; dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, blackening gingiva, stomatitis; obstructive thromboangitis, obstructive Skin ulcers, cold sensation, and numbness due to peripheral circulatory disorders such as arteriosclerosis, diabetic peripheral circulatory disorder, and varicose veins; Diseases; nervous system diseases such as neuralgia, polyneuritis, Smon's disease; dyskeratosis such as psoriasis, chicken eye, octopus, ichthyosis, palmoplantar keratosis, lichen, pityriasis; acne vulgaris; Purulent skin diseases such as impetigo, folliculitis, bunches, cough, cellulitis, pyoderma, purulent eczema; suppression of recurrent hair after hair removal (waste hair treatment); freckles, rough skin, dull skin The beauty of the skin and hair, such as the tension of the skin, the weakening of the gloss of the skin, the weakening of the gloss of the hair, etc. Use the possible treatment and prevention or improvement with little, also it is used in a desired site, provoking lean the site.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention can be used for athlete's foot, insect bites, atopic dermatitis, monetary eczema, xerosis, seborrheic eczema, urticaria, prurigo, housewife eczema, Acne vulgaris, impetigo, folliculitis, bunches, sclerosis, cellulitis, pyoderma, psoriasis, ichthyosis, palmoplantar keratosis, lichen, pityriasis, wounds,
When used for the treatment of skin mucosal diseases such as burns, cracks, erosion, and frost acne or itching associated with skin mucosal disorders, 0.2 mm or more, preferably 0.
5 mm or more, more preferably 1.0 mm or more, still more preferably 1.5 mm or more, and most preferably 2.0 mm or more in thickness, 2 minutes or more, preferably 3 minutes or more, more preferably 5 minutes or more, and still more preferably. Is applied for at least 10 minutes, most preferably at least 15 minutes. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The effect of the composition of the present invention can be obtained with only one application, but once to several times a day, once or more a week, preferably once every three days, more preferably once every two days, most preferably. Is applied daily until the itch disappears. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for treating mucous membrane damage such as pressure sores, wounds, burns, stomatitis, skin ulcers, cracks, erosions, frost acne and gangrene. Has a thickness of 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, still more preferably 2.0 mm or more, and most preferably 3.0 mm or more so as to completely cover the affected area. Minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and most preferably 20 minutes or more.
Apply for at least a minute until the injury has healed. For cases in which the damaged site is depressed from the surrounding skin mucosa, the damaged site is filled with the composition to be at the same height as the surrounding skin mucosal tissue, preferably at least 0.5 mm higher than the surrounding skin mucosal tissue, Preferably higher than the surrounding skin mucosal tissue by 1.0 mm or more,
More preferably 1.5 mm or more higher than the surrounding skin mucosal tissue, most preferably 2.0 mm higher than the surrounding skin mucosal tissue
Raise the composition above the injury site as high as above. If the composition is covered and adhered to the surrounding skin by a film made of a material having high tackiness and poor gas permeability, such as a film dressing material, and if the composition is sealed, the effect is further enhanced, The effect increases even when covered with a gas impermeable material such as a resin wrap film or vinyl. There is no problem even if it is applied continuously for 24 hours. In the case of pressure sores, etc., not only the effect is improved by long-time continuous application, but also nursing can be largely labor-saving. The composition of the present invention may be used once to several times a day once a week.
More than once, preferably once every three days, more preferably once every two days, most preferably daily, until the mucocutaneous damage has healed. After the application, rinse off with physiological saline, etc., or remove partially with clean gauze etc., then rinse with physiological saline, etc., and protect the affected area with a wound dressing, etc. After partially removing the composition, a new composition of the present invention may be additionally administered over the remaining composition.

When the composition for transdermal / transmucosal absorption of carbon dioxide of the present invention is used for promoting engraftment of transplanted skin pieces and flaps in a state of engraftment failure, or for the production of transplanted skin pieces and flaps etc. When used to prevent incomplete wearing, 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, even more preferably 2.0 m to completely cover the affected area
m or more, most preferably 3.0 mm or more, is applied for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and most preferably 20 minutes or more. The composition is covered with a film made of a material having poor gas permeability, such as a film dressing material, which is highly tacky and adheres to the surrounding skin,
The effect is further enhanced if the composition is sealed, but the effect is increased even if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl. There is no problem even if the coating is applied continuously for 24 hours or more, but the effect is enhanced by continuous coating for a long time. The composition of the present invention may be used once to several times a day at least once a week, preferably once every three days, more preferably once every two days.
Apply once, most preferably daily, until engraftment is complete. After application, rinse off with physiological saline, etc., or remove it partially with clean gauze etc., then rinse off with physiological saline, etc., and protect the affected area with a wound dressing, etc.
In the case of continuous administration, after partially removing the composition,
A new composition of the present invention may be additionally administered over the remaining composition.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for the treatment or prevention of dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, melanitis, stomatitis, etc. Or 0.5 mm or more, preferably 1.0 mm to completely cover the site where the disease is expected to occur
Above, more preferably 1.5 mm or more, still more preferably 2.0 mm or more, most preferably 3.0 mm or more in thickness, 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, most preferably Once a day for more than 20 minutes
It is applied several times at least once a week, preferably once every three days, more preferably once every two days, most preferably every day, until healing of the affected part is observed or no signs of disease appear.
After completion of the application, the composition in the mouth may be washed away by gargling or the like. However, the composition remains in the mouth without being completely washed away, and there is no problem in swallowing. In addition, the composition of the present invention has a very high fluidity, for example, a test method of Test Example 35 (an evaluation test of the fluidity of the composition) shows that the moving distance of the composition disk for 5 seconds is 30 cm.
In the case of the composition of the present invention described above, it can be used as a rinsing agent. In that case, the composition of the present invention is at least 5 g, preferably at least 10 g, more preferably at least 15 g, still more preferably at least 20 g, most preferably at least 30 g.
g or more is contained in the mouth so as to cover a desired site for 3 minutes or more, preferably 5 minutes or more, more preferably 10 minutes or more, still more preferably 15 minutes or more, and most preferably 20 minutes or more. After a predetermined period of time, the composition may be spit out and rinsed with water or the like, or may be left as it is without any particular problem.

The composition for transdermal / transmucosal absorption of carbon dioxide of the present invention may be used to treat skin ulcers or colds caused by peripheral circulatory disorders such as occlusive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory dysfunction, and varicose veins. When used for prevention or treatment of sensation and numbness, 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, and further preferably 1. A thickness of 5 mm or more, most preferably 2.0 mm or more, has a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more.
Apply for at least a minute. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is used once a day.
One to several applications are applied at least once a week, preferably once every three days, more preferably once every two days, most preferably every day, until healing of the affected area is observed or there is no sign of disease. After the application is completed, wiping, rinsing with water, or both may be performed.

The composition for transdermal / transmucosal absorption of carbon dioxide of the present invention may be used for musculoskeletal diseases such as rheumatoid arthritis, cervico-brachial syndrome, myalgia, arthralgia, lumbago, or neuralgia, polyneuritis, simon When used for treatment or prevention of nervous system diseases such as diseases, 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more to completely cover the affected area or a site where the disease is expected to occur , More preferably 1.5 mm or more, most preferably 2.0 m
m or more, is applied for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, further preferably 20 minutes or more, and most preferably 30 minutes or more. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced.
The composition of the present invention is used once or several times a day at least once a week, preferably once every three days, more preferably once every two days, and most preferably every day. Is applied until the sign of generation of elimination disappears. Wipe off after application,
Rinsing with water or the like or both may be performed.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for psoriasis, chicken eye, octopus, ichthyosis, palmoplantar keratosis, lichen,
When used in the treatment of dyskeratosis such as pityriasis, 0.2 mm or more, preferably 0.5 mm to completely cover the affected area
mm or more, more preferably 1.0 mm or more, still more preferably 1.5 mm or more, most preferably 2.0 mm or more in thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and still more preferably. Is applied for at least 20 minutes, most preferably at least 30 minutes. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is applied once to several times a day at least once a week, preferably once every three days, more preferably once every two days, most preferably every day until healing is confirmed. After the application is completed, wiping, rinsing with water, or both may be performed.

The composition for transdermal and transmucosal absorption of carbon dioxide of the present invention may be treated with acne vulgaris, impetigo, folliculitis, bunches, cough, cellulitis, pyoderma, purulent eczema, etc. When used for the treatment of skin diseases, 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more to completely cover the affected area.
mm or more, more preferably 2.0 mm or more, most preferably 3.0 mm or more, having a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably Apply for at least 30 minutes.
At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention may be used once to several times a day at least once a week, preferably once every three days, more preferably once every two days.
Apply once, most preferably daily, until healing is confirmed. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for suppressing recurring hair after hair removal (wasted hair treatment), shaving off unwanted hair at a desired site with a razor or the like, or After removing the hair with a hair remover or the like, 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, still more preferably 2.0 mm or more, most preferably so as to completely cover the hair removal site. A thickness of 3.0 mm or more has a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more.
Apply for at least a minute. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is used once a day.
Times to several times at least once a week, preferably once every three days, more preferably once every two days, most preferably every day, the total number of applications is 10 or more, preferably 15 or more, more preferably 20 or more. More than 30 times, most preferably more than 30 times. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for the purpose of reducing freckles or making it less noticeable, the composition may be applied so as to cover only desired portions. Because the effect of improving partial obesity and the like appear simultaneously in the application site, as wide as possible, for example, in the case of a face, 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more,
It is more preferably at least 2.0 mm, most preferably 3.
A thickness of 0 mm or more has a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and still more preferably 20 minutes or more.
Minutes or more, most preferably 30 minutes or more. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention may be used once to several times a day at least once a week, preferably once every three days, more preferably once every two days, most preferably every day, and the total number of applications is preferably ten times or more, preferably Is applied 15 times or more, more preferably 20 times or more, and most preferably 30 times or more. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for the purpose of whitening, tightening the skin and improving skin quality, the composition is preferably 0.2 mm or more, preferably 0.1 mm or more, so as to cover a desired site. 5 mm or more, more preferably 1.0 mm or more,
More preferably 1.5 mm or more, most preferably 2.
A thickness of 0 mm or more has a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and still more preferably 20 minutes or more.
Minutes or more, most preferably 30 minutes or more. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced.
The term "improvement of skin quality" as used in the present invention means that the skin is smooth, fine, transparent, and has good makeup. The whitening effect, the skin tightening effect, and the skin quality improving effect can be obtained only by applying the composition of the present invention once, but once to several times a day at least once a week, preferably once every three days. More preferably, once every two days, most preferably daily, as long as possible. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for the purpose of rejuvenating skin, the composition is preferably 0.2 mm or more, more preferably 0.5 mm or more so as to cover a desired site. A thickness of 1.0 mm or more, more preferably 1.5 mm or more, most preferably 2.0 mm or more, has a thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably Preferably, it is applied for 30 minutes or more. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The skin rejuvenation referred to in the present invention refers to skin with microscopic skin surface, in which the crevices and pits disappear or are indistinct, and the skin in which exfoliation of keratin occurs partially or widely is formed by dermis and pits. To make the skin clear and tidy. The composition of the present invention may be used once to several times a day,
At least once a day, more preferably at least once every two days, most preferably every day, the total number of applications is at least 10 times, preferably 1
The coating is performed 5 times or more, more preferably 20 times or more, and most preferably 30 times or more. After the application is completed, wiping, rinsing with water, or both may be performed.

When the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is used for the purpose of improving partial obesity of the face, legs, arms, abdomen, flanks, back, neck, jaw, etc., a desired site may be used. 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, even more preferably 1.5 mm or more, and most preferably 2.0 mm or more to cover 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, most preferably 30 minutes or more, once to several times a day, at least once every three days, more preferably at least once every two days, Most preferably, the total number of application times is 20 times or more, preferably 25 times or more, most preferably 30 times or more every day. At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. After the application is completed, wiping, rinsing with water, or both may be performed.

The composition of the present invention has an action of removing dullness of the skin, and a whitening effect can be obtained with a single application. These parts can be made healthy. In this case, the composition of the present invention is 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more so as to completely cover the desired site.
mm or more, more preferably 1.5 mm or more, most preferably 2.0 mm or more in thickness of 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably It is applied for at least 30 minutes, once to several times a day, at least once every three days, more preferably at least once every two days, most preferably every day, until the effect appears.
At this time, if the composition is covered with a gas impermeable substance such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. After the application is completed, wiping, rinsing with water, or both may be performed.

As shown in the results of Test Example 42,
Since the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention to which the herb extract has been added has a stronger whitening effect than the composition to which it has not been added, it is considered that the composition has an absorption promoting effect of the herb extract. From this fact, by adding a physiologically active substance to the composition of the present invention, the transdermally absorbable component is further improved in absorption efficiency, the effect is easily obtained, and the physiologically active substance which has conventionally been considered difficult to transdermally absorb. It is expected that transdermal absorption of the substance will be possible. Transdermal absorption in this case also includes transmucosal absorption. Since the dose reduction is expected due to the improvement of the absorption efficiency of the physiologically active substance, the reduction of side effects is also expected. Further, since the composition of the present invention not only promotes absorption of a physiologically active substance without destroying stratum corneum as in the case of conventional percutaneous absorption preparations, but also has a healing promoting action on broken or damaged skin and mucous membranes, Transdermal preparations containing the composition of the present invention containing a physiologically active substance are expected to reduce or avoid side effects such as rash seen in conventional products. Fluocinolone acetonide as a physiologically active substance in a transdermal absorption preparation containing the composition of the present invention, fluocinonide,
Betamethasone valerate, betamethasone dipropionate, betamethasone propionate, hydrocortisone acetate,
Prednisolone, methylprednisolone, methylprednisolone acetate, methylprednisolone acetate, dexamethasone, dexamethasone valerate, dexamethasone propionate, fludoxycortide, flumethasone pivalate,
Beclomethasone propionate, hydrocortisone butyrate, clobetasol propionate, triflucinolone acetonide diflucortron valerate, halcinonide, prednisolone acetate valerate, amcinonide, hydrocortisone propionate butyrate, clobetasone butyrate, diflorazone acetate, diflupredroneclosone, propionate dimethionate Steroids such as deprodone propionate and mometasone furoate 0.01 to 5% by weight, kanamycin sulfate, fradiomycin sulfate, gentamicin sulfate, erythromycin, tetracycline hydrochloride, oxytetracycline hydrochloride, chloramphenicol, bacitracin, ofloxacin, nadifloxacin, etc. 0.1 to 10% by weight of nystatin, tricomycin, Runafutato, nitric isoconazole, Torushikurato, tioconazole, sulconazole nitrate, nitrate oxiconazole, hydrochloric cloconazole,
Bifonazole, ketoconazole, butenafine hydrochloride,
Antifungal drugs such as neticonazole hydrochloride, terbinafine hydrochloride, lanconazole, amorolfine hydrochloride, econazole nitrate, clotrimazole, pimaricin, miconazole nitrate, tolnaftate, and ciclopirox olamine.
0.1 to 5% by weight, 0.1 to 10% by weight of a local anesthetic such as oxybuprocaine hydrochloride, ethyl aminobenzoate, cocaine hydrochloride, lidocaine hydrochloride, dibucaine hydrochloride, and 0.1 to 0.1% by weight of a cell activator such as tocoretinate or bucladesine. ~ 2
0% by weight, 0.1 to 10% by weight of coronary vasodilators such as nitroglycerin and isosorbide dinitrate, calcium antagonists such as nifedipine, epinephrine, ephedrine hydrochloride, methoxyphenamine hydrochloride, isoprenaline sulfate, isoprenaline hydrochloride, orciprenaline sulfate, 0.1 β-stimulants such as chlorprenaline hydrochloride, trimethoquinol hydrochloride, salbutamol sulfate, terbutaline sulfate, procaterol hydrochloride, pyrbuterol hydrochloride, fenoterol hydrobromide, formoterol fumarate, clenbuterol hydrochloride, mabuterol hydrochloride, diprofylline, etc. 10 to 10% by weight, 1 to 15% by weight of an antitussive expectorant such as Shazenso extract, spruce extract, ginger extract, ephedra extract, etc., but transdermal absorption is possible even with physiologically active substances other than those exemplified here. Or transdermal absorption efficient percutaneous absorption is expected by blending the compositions of the present invention as long as the physiologically active substance to be expected.

[0079]

(Evaluation of composition for carbon dioxide transdermal and transmucosal absorption)

<Foamability> 50 g of basic composition and 1 g of acid are 5 cm in diameter,
Place in a 10 cm high cup and measure its volume. This is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

[0080] For the measurement of the volume, the height of the composition for carbon dioxide transdermal / transmucosal absorption at each measurement point is noted in a cup, water is added to the height after removing the composition, and the water The volume is measured with a measuring cylinder. <Persistence of air bubbles> 50 g of the basic composition and 1 g of the acid are mixed with a diameter of 5
into a cup having a height of 10 cm and a height of 10 cm, and stirred and mixed 20 times for 10 seconds to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition was measured.
The volume after time is measured, the rate of decrease in volume is determined in percent, and the continuity of the bubbles is evaluated in accordance with Evaluation Criteria 2.

<Evaluation Criteria 2> Reduction Rate Persistence of air bubbles 20% or less +++ 20% to 40% ++ 40% to 60% + 60% or more Measurement of 0 volumes is performed by transcutaneous carbon dioxide at each measurement time. The height of the composition for transmucosal absorption is noted on a cup, water is added to the height after removing the composition, and the volume of the water is measured with a measuring cylinder.

[0082]

[Table 1]

[0083]

[Table 2]

[0084]

[Table 3]

[0085]

[Table 4]

[0086]

[Table 5]

[0087]

[Table 6]

[0088]

[Table 7]

Examples 85-108 Tables 8 and 9 show compositions for transdermal and transmucosal absorption of carbon dioxide which consist of a combination of an acidic composition and a carbonate. [Production Method] A thickener, purified water, and an acid (organic acid and / or inorganic acid) are combined as shown in Tables 8 and 9 to prepare an acidic composition in advance. The carbonate can be used as it is, or in the case of crystals, pulverized, or dissolved or dispersed in an appropriate solvent. The acidic composition and the carbonate are mixed to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. <Production of acidic composition> In a container such as a beaker, a thickener is dissolved or swelled in purified water to dissolve or disperse an acid. At this time, if necessary, purified water may be heated to promote dissolution and swelling of the thickener, or the thickener may be dissolved or dispersed in an appropriate solvent before use. If necessary, suitable additives and medicinal substances may be added thereto. [Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide] <Effervescent property> 50 g of acidic composition and 1.2 g of carbonate were used to obtain a powder having a diameter of 5
cm, placed in a 10 cm high cup and measure its volume. This is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, and foamability is evaluated according to Evaluation Criteria 1. The volume is measured in accordance with the method described in <Effervescent> in Examples 1 to 84 [Evaluation of the composition for transdermal / transmucosal absorption of carbon dioxide]. <Persistence of air bubbles> 50 g of the acidic composition and 1.2 g of the carbonate are put into a cup having a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times for 10 seconds to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, and two hours after that, the volume is measured to determine the rate of decrease in volume in percent.
The measurement of the volume is carried out according to the method described in <Evaluation of the composition for transdermal / transmucosal absorption of carbon dioxide> in Examples 1 to 84, <Persistence of air bubbles>.

[0090]

[Table 8]

[0091]

[Table 9]

Examples 109 to 144 Tables 10 to 12 show compositions for transdermal and transmucosal absorption of carbon dioxide which consist of a combination of a basic composition and an acid granule. [Production method] A thickener and purified water, a carbonate and an acid (organic acid and / or inorganic acid), a matrix base are combined as shown in Tables 10 to 12, and a basic composition and an acid granule are prepared in advance. Prepare. The granules may be sustained release. The basic composition and the acid granule are mixed to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. The matrix base referred to in the present invention is a compound which is fluidized by dissolution or swelling with a solvent, melted by heating, and contains other compounds, then solidified by removing the solvent or cooling, and forming a granule by pulverization or the like, Alternatively, it refers to any compound that mixes with another compound, compresses, solidifies, and forms granules by pulverization or the like, which dissolves or disintegrates with water. Matrix bases include ethyl cellulose, erythritol, carboxymethyl starch and its salts, carboxymethyl cellulose and its salts, hydrous silicon dioxide, xylitol, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, synthetic hydrotal Site, stearyl alcohol, cetanol, sorbitol, dextrin, starch, lactose, sucrose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, pullulan, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone , Mannose, methylcellulose, etc. Is, these one or more is used. <Production of basic composition> The basic composition is produced according to the method for producing a basic composition described in Examples 1 to 84. <Production of Acid Granule> When a low-melting point compound is used as the matrix base, the acid is added to the low-melting-point matrix base melted by heating in a vessel such as a beaker, and the mixture is sufficiently stirred and mixed. If necessary, suitable additives and medicinal substances may be added thereto. This is further stirred while gradually cooling it at room temperature, and allowed to stand until it hardens. When it has hardened to some extent, it may be cooled rapidly in a refrigerator or the like. When a low-melting point compound is not used as the matrix base, the matrix base is dissolved or dispersed in a suitable solvent such as water or ethanol in a container such as a beaker, and the acid is dissolved or dispersed therein and thoroughly mixed. Thereafter, the mixture is heated in an oven or the like to remove the solvent and dried. When completely hardened, it is ground into granules. At this time, the granules may be sieved to make them uniform in size.

In the present invention, the method for producing the above-mentioned acid granules is not limited to the present Example, but includes dry crushing granulation, wet crushing granulation, fluidized bed granulation, high-speed stirring granulation. It can be manufactured according to a conventional method such as a granulation method and an extrusion granulation method. [Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide] <Effervescent> 50 g of a basic composition and 1 g of an acid equivalent of an acid granule were placed in a cup having a diameter of 5 cm and a height of 10 cm, and the volume was measured. I do. This is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. Stir and mix 1
After minutes, the volume of the composition is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

The volume is measured according to the method described in <Effervescent> in Examples 1 to 84 [Evaluation of the composition for transdermal and transmucosal absorption of carbon dioxide]. <Persistence of air bubbles> 50 g of a basic composition and 1 g of an acid equivalent to an acid granule are placed in a cup having a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times in 10 seconds to absorb carbon dioxide percutaneously and transmucosally. Obtain the composition. One minute after stirring and mixing, the volume of the composition is measured, and two hours after that, the volume is measured to determine the rate of decrease in volume in percent.

The measurement of the volume is carried out according to the method described in <Evaluation of the composition for transdermal and transmucosal absorption of carbon dioxide> of <Examples 1 to 84><Persistence of air bubbles>.

[0096]

[Table 10]

[0097]

[Table 11]

[0098]

[Table 12]

Examples 145 to 179 Tables 13 to 15 show compositions for transdermal and transmucosal absorption of carbon dioxide which consist of a combination of an acidic composition and a granule of carbonate. [Production method] A thickener and purified water, a carbonate and an acid (organic acid and / or inorganic acid), a matrix base are combined as shown in Tables 13 to 15, and an acidic composition and a granule of a carbonate are prepared in advance. Prepare. The granules may be sustained release. The acidic composition and the granules of carbonate are mixed to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. <Production of acidic composition> The acidic composition is produced according to the method for producing an acidic composition described in Examples 85 to 108. <Production of Granules of Carbonate> When a low melting point compound is used as the matrix base, the carbonate is added to the low melting point matrix base which is melted by heating in a vessel such as a beaker, and then sufficiently stirred and mixed. If necessary, an appropriate additive or medicinal substance may be added thereto. This is further stirred while gradually cooling it at room temperature, and allowed to stand until it hardens. When it has hardened to some extent, it may be cooled rapidly in a refrigerator or the like. If a low melting point compound is not used as the matrix base, dissolve or disperse the matrix base in a suitable solvent such as water or ethanol in a container such as a beaker, and dissolve or disperse the carbonate in this, and mix well. After that, the mixture is heated in an oven or the like to remove the solvent and dried. When completely hardened, crush,
Granules. At this time, the granules may be sieved to make them uniform in size.

In the present invention, the method for producing the above-mentioned carbonate granules is not limited to the present Example, but includes dry crushing granulation, wet crushing granulation, fluidized bed granulation, high-speed stirring, and the like. It can be manufactured according to a conventional method such as a granulation method and an extrusion granulation method. [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] <Effervescent> 50 g of acidic composition and 1.2 g of carbonate equivalent of granules of carbonate were put into a cup having a diameter of 5 cm and a height of 10 cm, and Measure the volume. This is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal / transmucosal absorption of carbon dioxide.
One minute after stirring and mixing, the volume of the composition is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

The volume is measured according to the method described in <Effervescence> in Examples 1 to 84 [Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]. <Persistence of air bubbles> 50 g of the acidic composition and 1.2 g of the carbonate equivalent of carbonate granules were placed in a cup having a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times for 10 seconds, followed by transdermal carbon dioxide / transdermal delivery. A composition for mucosal absorption is obtained. One minute after stirring and mixing, the volume of the composition is measured, and two hours after that, the volume is measured to determine the rate of decrease in volume in percent.

The volume is measured according to the method described in <Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide> in <Examples 1 to 84><Persistence of air bubbles>.

[0103]

[Table 13]

[0104]

[Table 14]

[0105]

[Table 15]

Examples 180 to 226 Tables 16 to 19 show compositions for transdermal and transmucosal absorption of carbon dioxide which consist of a combination of an acidic composition and a basic composition. [Production method] A thickener and purified water, a carbonate and an acid (organic acid and / or inorganic acid) are combined as shown in Tables 16 to 19,
An acidic composition and a basic composition are prepared in advance. The acidic composition and the basic composition are mixed to obtain a composition for transdermal / mucosal absorption of carbon dioxide. <Production of acidic composition> The acidic composition is produced according to the method for producing an acidic composition described in Examples 85 to 108. <Production of basic composition> The basic composition is produced according to the method for producing a basic composition described in Examples 1 to 84. [Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide] <Effervescent property> 25 g of an acidic composition and 25 g of a basic composition are put into a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

The volume is measured in accordance with the method described in <Effervescent> in Examples 1 to 84 [Evaluation of the composition for transdermal and transmucosal absorption of carbon dioxide]. <Bubble persistence> 25 g of acidic composition and 25 of basic composition
g into a cup having a diameter of 5 cm and a height of 10 cm.
Stir and mix 20 times per second to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, and two hours after that, the volume is measured to determine the rate of decrease in volume in percent.

The volume is measured according to the method described in <Evaluation of a composition for transdermal and transmucosal absorption of carbon dioxide> of <Examples 1 to 84><Persistence of air bubbles>.

[0109]

[Table 16]

[0110]

[Table 17]

[0111]

[Table 18]

[0112]

[Table 19]

Examples 227 to 249 The compositions for transdermal and transmucosal absorption of carbon dioxide comprising a combination of composite granules of carbonate and acid and a viscous composition containing water are shown in Table 20.
To Table 21. [Production method] A thickener and purified water, a carbonate and an acid (organic acid and / or inorganic acid), a matrix base are combined as shown in Tables 20 to 21, and a composite granule of carbonate and acid and water-containing viscosity The composition is prepared beforehand. The composite granule of carbonate and acid is mixed with the water-containing viscous composition to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. The composite granules of carbonate and acid may have a sustained release of carbonate and acid. <Production of composite granules of carbonate and acid> When a low melting point compound is used as a matrix base, a carbonate and an acid are sufficiently added to a low melting point matrix base that is melted by heating in a container such as a beaker. Stir and mix. If necessary, suitable additives and medicinal substances may be added thereto. This is further stirred while gradually cooling it at room temperature, and allowed to stand until it hardens. When it has hardened to some extent, it may be cooled rapidly in a refrigerator or the like. When a low melting point compound is not used as the matrix base, the matrix base is dissolved or dispersed in a suitable solvent such as anhydrous ethanol in a container such as a beaker, and the carbonate and the acid are dissolved or dispersed, and after sufficient mixing, The solvent is removed by heating in an oven or the like and dried. When completely set, pulverize into granules. At this time, the granules may be sieved to make them uniform in size. <Production of water-containing viscous composition> A thickener is dissolved or swelled in purified water in a container such as a beaker. At this time, if necessary, purified water may be heated to promote the dissolution or swelling of the thickener, or the thickener may be dissolved or dispersed in an appropriate solvent before use. If necessary, suitable additives and medicinal substances may be added thereto.

In the present invention, the method for producing the above composite granules of carbonate and acid is not limited to the present Example, but includes dry crushing granulation, fluidized bed granulation, high-speed stirring granulation, and the like.
It can be manufactured according to a conventional method such as an extrusion granulation method. [Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide] <Effervescent> 50 g of a water-containing viscous composition and 1.2 g of a carbonate and a complex granule of a carbonate and an acid equivalent to 1.2 g of a carbonate had a diameter of 5 cm and a height of 10 cm.
Put into a cm cup and measure its volume. The mixture of the water-containing viscous composition and the composite granules of carbonate and acid is applied for 2 seconds in 10 seconds.
Stir and mix 0 times to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition was measured, the rate of increase from the volume before stirring and mixing was determined in percent, and the rate of increase from the volume before stirring and mixing was determined in percent.
The foamability is evaluated according to the following.

The volume is measured according to the method described in <Effervescent> in [Evaluation of the composition for transdermal / transmucosal absorption of carbon dioxide] in Examples 1 to 84. <Bubble persistence> 50 g of the water-containing viscous composition and carbonate 1.2
g of a complex granule of carbonate and acid is placed in a cup having a diameter of 5 cm and a height of 10 cm, and the mixture is stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. One minute after stirring and mixing, the volume of the composition is measured, and two hours after that, the volume is measured to determine the rate of decrease in volume in percent.

The volume is measured according to the method described in <Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide> in <Examples 1 to 84><Persistence of air bubbles>.

[0117]

[Table 20]

[0118]

[Table 21]

Examples 250 to 272 Tables 22 to 23 show compositions for transdermal and transmucosal absorption of carbon dioxide which consist of a combination of a basic composition and an acid-containing sheet. [Production method] carbonate and acid (organic acid and / or inorganic acid),
A thickener, a matrix base, and purified water are combined as shown in Tables 22 to 23 to prepare a basic composition and an acid-containing sheet in advance. The base composition is brought into contact with the acid-containing sheet to obtain a composition for transdermal and transmucosal absorption of carbon dioxide. <Production of basic composition> The basic composition is produced according to the method for producing a basic composition described in Examples 1 to 84. <Manufacture of acid-containing sheet> In a container such as a beaker, dissolve or disperse the matrix base in a solvent such as water or ethanol, dissolve or disperse the acid therein, and form a uniform thickness on a glass plate as needed. To an appropriate size and dried in an oven or the like to obtain an acid-containing sheet. If necessary, suitable additives and medicinal substances may be added thereto. In addition, a nonwoven fabric, a woven fabric, a polymer film, or the like may be used as the support, and an adhesive may be applied around the support to form a patch. [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] <Foamability> 50 g of a basic composition was placed on a glass plate at a side of 10 g.
A square sheet having a uniform thickness of 10 cm and containing 1 g of acid is placed thereon. After 5 minutes, those having bubbles at the interface between the sheet and the basic composition are evaluated as foaming “○”, and those not observed are evaluated as foaming “X”. <Persistence of Bubble> 50 g of the basic composition is spread on a glass plate into a square having a uniform thickness of 10 cm on a side, and a 10 cm-square acid-containing sheet containing 1 g of acid is placed thereon. After 5 minutes and 2 hours, air bubbles were observed at the interface between the sheet and the basic composition, and the sustainability of the air bubbles was evaluated as “○”. After 5 minutes, air bubbles were observed. Is evaluated as a bubble sustainability “x”.

[0120]

[Table 22]

[0121]

[Table 23]

Examples 273 to 294 Tables 24 to 25 show compositions for transdermal and transmucosal absorption of carbon dioxide, which consist of a combination of an acidic composition and a carbonate-containing sheet. [Production method] carbonate and acid (organic acid and / or inorganic acid),
A thickener, a matrix base, and purified water are combined as shown in Tables 24 to 25 to prepare an acidic composition and a carbonate-containing sheet in advance. The acidic composition is brought into contact with the carbonate-containing sheet to obtain a composition for transdermal / transmucosal absorption of carbon dioxide. <Production of acidic composition> The acidic composition is produced according to the method for producing an acidic composition described in Examples 85 to 108. <Manufacture of carbonate-containing sheet> The matrix base is dissolved or dispersed in a solvent such as water or ethanol in a container such as a beaker, and the carbonate is dissolved or dispersed in the matrix base. And then dried in an oven or the like to obtain a carbonate-containing sheet. If necessary, suitable additives and medicinal substances may be added thereto.
In addition, a nonwoven fabric, a woven fabric, a polymer film, or the like may be used as the support, and an adhesive may be applied around the support to form a patch. [Evaluation of composition for transdermal / transmucosal absorption of carbon dioxide] <Foamability> 50 g of acidic composition was placed on a glass plate at 10 c per side.
m and stretched into a square having a uniform thickness.
A square carbonate-containing sheet of 10 cm on a side containing 2 g is placed. After 5 minutes, those having bubbles at the interface between the sheet and the acidic composition are evaluated as foaming “「 ”, and those not observed are evaluated as foaming“ X ”. <Persistence of air bubbles> 50 g of the acidic composition is spread on a glass plate into a square having a uniform thickness of 10 cm on a side, and a square carbonate-containing sheet having a side of 10 cm and containing 1.2 g of a carbonate is placed thereon. After 5 minutes and 2 hours, air bubbles were observed at the interface between the sheet and the acidic composition. The sustainability of the air bubbles was evaluated as “」 ”. After 5 minutes, air bubbles were observed. Those which were not recognized are evaluated as the bubble persistence “x”.

[0123]

[Table 24]

[0124]

[Table 25]

Example 295 (Composition for transdermal / transmucosal absorption of carbon dioxide for occlusive therapy consisting of a combination of carbonate, acid and water-containing viscous composition) [Production method] 0.24 g of sodium bicarbonate and 0.1% of citric acid. 2 g, and spread evenly inside 2 cm from the end of the adhesive surface of a 6 cm × 7 cm film dressing material (trade name: Tegaderm, 3M), and 5 cm × 6 c from above
m, and adhere the nonwoven fabric to the adhesive surface of the film dressing so that the mixture of sodium bicarbonate and citric acid does not spill. On the nonwoven fabric, <Production of water-containing viscous composition> of Examples 227 to 249
0.3 g of sodium alginate and sodium carboxymethylcellulose 0.
A water-containing viscous composition comprising 2 g and 9.5 g of purified water is applied to a uniform thickness 1 cm inward from the end of the nonwoven fabric to obtain a composition for transdermal / transmucosal absorption of carbon dioxide for occlusive therapy. Example 296 (Composition for Transdermal / Transmucosal Absorption of Carbon Dioxide for Occlusion Therapy Consisting of Combination of Complex Granules of Carbonate and Acid and Hydrous Viscous Composition) [Production Method] 5 g of cetanol was placed in a 100 ml beaker in a warm bath. Melt, add 24g of sodium bicarbonate
And 20 g of citric acid, and stir well. When these are sufficiently mixed, they are further stirred while gradually cooling at room temperature. When they have hardened to some extent, stop stirring and leave them until they are completely hardened. When completely solidified, it is pulverized to obtain a composite granule of carbonate and acid.

0.49 g of the composite granule was weighed 6 cm × 7 cm
Film dressing material (trade name: Tegaderm, 3M Company)
Spread thinly 2cm inside from the edge of the adhesive surface of
Cover with a thin non-woven fabric of 5 cm x 6 cm.
This non-woven fabric is coated with the film dressing so that the agent does not spill.
Adhere to the sticky surface of the shinging material. Example 2 on the nonwoven fabric
27 to 249 <Production of water-containing viscous composition>
0.3 g of sodium alginate prepared according to the method
0.2 g of sodium ruboxylmethylcellulose, purified water
1 c from the end of the non-woven fabric
内側 Apply uniform thickness on the inside and use carbon dioxide
A composition for transdermal / transmucosal absorption is obtained. Example 297 (Combination of basic composition and acid-coated granule)
Composition for carbon dioxide transdermal / transmucosal absorption consisting of blending) [Production method] Mix and stir a basic composition and acid-coated granules
Then, a composition for transdermal and transmucosal absorption of carbon dioxide is obtained. this
These mixing ratios can be arbitrarily set, but 1.2 parts by weight of carbonate
Acid-coated condyles equivalent to 1 part by weight of acid for a considerable basic composition
Grains are used in the test examples. <Production of basic composition> 2 g of methyl paraben, hydrogen carbonate
24g sodium, carboxymethyl starch sodium
40 g, sodium alginate 40 g, carboxyme
40 g of sodium butylcellulose in 2,000 ml of water
Dissolved or dispersed in water and stirred well to obtain a basic composition.
You. Add appropriate additives and medicinal substances to this as necessary.
You may get. <Production of acid-coated granules> Citric acid 1.8 k
g was dissolved in 722 g of a 7% HPC-L ethanol solution.
The solution was purified using a CF granulator to obtain purified sucrose granules (trade name).
Product name Nonpareil 103, Freund Corporation) 9k
g, and after drying, obtain 10.7 kg of acid-coated granules.
Was. Example 298 (Water-containing viscous composition containing carbonate and vegetable essential oil)
And carbon dioxide transdermal consisting of a combination of
Transmucosal composition) [Production method] 1 g of methyl paraben, sodium hydrogen carbonate
12 g, sodium carboxymethyl starch 25 g,
Sodium alginate 20g, carboxymethyl cellulose
Sodium 25g, grapefruit oil 0.5m
1, cajeput oil 0.1 ml, rosewood oil 0.1 m
1, geranium oil 0.1 ml, edible green pigment 0.01
g, 1 ml of alpha tocopherol acetate
Dissolve or disperse in water and mix well. As needed
Then, an appropriate additive, a medicinal substance and the like may be added thereto.
1.2 g of the acid-coated granules of Example 297 were added to the 25 g.
From the composition for carbon dioxide transdermal and transmucosal absorption
To get a cream. Example 299 (a sample composed of a water-containing viscous composition and carbon dioxide)
Composition for transdermal / transmucosal absorption of carbon oxide) [Production method] 12 g of sodium hydrogen carbonate, carboxyme
Chillstarch sodium 20g, sodium alginate
20 g is dissolved in 1,000 ml of water to obtain a water-containing viscous composition.
Get. A small carbon dioxide cylinder (trade name: Tetra C)
O2 cylinder, manufactured by Warner Lambert)
6.0mm diameter, 3.5mm inner diameter, 60cm long vinyl
Insert the tip of the tube and blow in carbon dioxide
Add 20 g of sodium carboxymethylcellulose
By dissolving with stirring, carbon dioxide transdermal
A composition for membrane absorption is obtained. Test Example 1 (Treatment test for itch associated with tinea pedis) A 41-year-old man. For tinea pedis on the right foot with severe itching
Fill the basin with 100 g of the composition of Example 8 and let the feet stand for about 20 minutes
When soaked for a while, itchy after one treatment with this composition
Was taken. Test Example 2 (Treatment test for itch associated with tinea pedis) A 73-year-old woman. Against tinea pedis on both feet with very strong itching
Then, the basin was filled with 300 g of the composition of Example 18 and
Was soaked for about 20 minutes. 2 years of topical antifungal
The treatment was completely ineffective, but once treated with the composition
The itch was removed by treatment. Test Example 3 (Stomatitis treatment test) A 41-year-old man. 1 g of the composition of Example 8 for stomatitis for 10 minutes
When applied, the pain disappears, the wound closes and heals
did. Test Example 4 (Pulmonary wound treatment test) A 78-year-old man. As the lung cancer progresses, she becomes bedridden,
A pressure sore developed from the to the buttocks. The pressure sore depth is about 4c
m to the fascia. 100 g of the composition of Example 1
Fill the pocket of pressure sore, fill 20cm x 30cm
2 with mud dressing material (trade name: Tegaderm, 3M)
Covered for 0 minutes. The composition and film dressing material
Exchanged days. The depth of the pressure sore is 1cm on the 11th day of treatment
Improved. One month after the start of treatment, granulation is almost around
Raised to the same height as normal skin. Test Example 5 (Zuck shoe dermatitis treatment test) An 8-year-old male. Zuk shoe dermatitis causes both soles to bleed and
Topical steroids (brand name Rinderon V ointment, Shionogi & Co., Ltd.)
Was applied for two months, but had no effect. Example 2
30 g of the composition of No. 0 applied to the sole once a day for 10 minutes
The wound was closed on the fourth day and healed completely in one month
Was. Test Example 6 (Test for Gloss of Hair) 41-year-old man. My hair looks dull and looks old
20 g of the composition of Example 18 for 1 day
When applied to hair every day for about 15 minutes once, from day 3
The gloss of my hair has improved. Test Example 7 (Atopic dermatitis treatment test) A 4-year-old woman. Example 2 against atopic dermatitis of both knees
0 g once daily for 5 minutes.
Of course, the darkening of the skin disappears in 2 weeks, and the skin dries in 4 weeks
Has healed. Test Example 8 (partial thinning of face and abdomen) 41-year-old man. Thin your plump cheeks and thick waist
If desired, apply the composition of Example 8 once a day for 15 minutes.
Every day, 30 g was applied to the right cheek and 100 g to the abdomen. Two months later
Right cheek apparently smaller by all five evaluators
It was determined. The waist of the abdomen was reduced by 6 cm. Test Example 9 (Skin quality improvement and face thinning test) 37-year-old woman. Plump cheeks, rough and dull skin
As a result, various cosmetics were tried, but no effect was obtained. Real
Apply 50 g of the composition of Example 20 once a day for 10 minutes every day
When applied to the body, dull skin disappears with the first application
And became white and fine skin. 3 people after 2 weeks
All evaluators judged that the face was smaller. Test Example 10 (cervical-shoulder-arm syndrome treatment test) A 42-year-old man. Neck and shoulder arm disease caused by fatigue of computer operation
Anti-inflammatory agent for external use (Tiger brand name)
Balm, Ryukakusansha) was applied, but no effect was obtained.
won. 40 g of the composition of Example 20 is applied to the shoulder for 20 minutes
The cervical-shoulder-arm syndrome healed. Test Example 11 (Psoriasis vulgaris treatment test) 37-year-old woman. Against psoriasis vulgaris in the knee with very strong itching
And 3 g of the composition of Example 20 once a day for 10 minutes every day.
Applied. The itch disappeared with one application. 2 weeks later
The darkening of some parts improved. Test Example 12 (Fish Eye Treatment Test) 37-year-old female. To the chicken eye formed on the right side of the painful left toe
2 g of the composition of Example 20 was applied once a day for 10 minutes for 5 days.
When the cloth is spread, the positive around the eyes like a salicylic acid preparation
The normal skin healed without damage. Test Example 13 (Partial arm thinning test) 36-year-old woman. Example because I was concerned about the thickness of the upper arm
Apply 30 g of the composition No. 18 to the left upper arm and use it for food packaging
Film (trade name Saran Wrap, manufactured by Asahi Kasei Corporation)
After leaving for 6 hours, the circumference of the upper arm is 2
cm. Test Example 14 (Suppurative Eczema Treatment Test) 29-year-old man. Performed for purulent eczema on the entire buttocks
40 g of the composition of Example 18 was applied once a day for 20 minutes for 7 days
The suppurative eczema was cured. Test Example 15 (Insect biting itch treatment test) 51-year-old woman. Anti-His is stabbed in two places of arm and finger by bee
Tamine (brand name Celestamine Tablets, Schering-Plough)
) And a topical steroid (Teracortril)
Ointment, Pfizer Pharmaceutical Co., Ltd.)
The redness disappeared, but itching gradually appeared, and itching 2 weeks later
I became insomnia because of my eyes. Composition of Example 18
5 g of the product was applied for 15 minutes, the itch disappeared,
Was obtained. Test Example 16 (Treatment test for itch associated with tinea pedis) A 32-year-old woman. Against tinea pedis on both feet with very strong itching
And antifungal agent (Mentax Cream, Kaken Pharmaceutical Co., Ltd.)
Was applied for 2 months, but the itch did not subside at all
Did not. Fill a basin with 100 g of the composition of Example 8
Soaked feet for about 20 minutes
Was taken. Four days later, 100 m of the composition of Example 8 was used again.
1 filled the basin and soaked the feet for about 20 minutes
Of course, the gross findings of the lesions also improved markedly. Test Example 17 (Palm pad pustulosis treatment test) A 22-year-old woman. For palmar pustulosis with both hands with strong itching,
Fill a wash basin with 100 g of the composition of Example 18 and
After immersion for 15 minutes, the itch disappeared immediately. Test Example 18 (Atopic dermatitis treatment test) An 8-year-old male. Very strong pain and itch with some keratinization and cracks
Composition 5 of Example 8 against atopic dermatitis of fingers
Fill the cup with 0g and soak the fingertip for 20 minutes
However, the itch disappeared immediately. The next day, epithelium forms in the crack
And pain was reduced. Test Example 19 (Psoriasis vulgaris treatment test) 37-year-old woman. Against psoriasis vulgaris in the knee with very strong itching
Then, apply 10.49 g of the composition of Example 296 for 30 minutes.
did. Itching disappeared immediately, and keratinization and drying of the affected epithelium were marked.
Clearly improved. Test Example 20 (face abrasion treatment test) 10-year-old male. For a 3cm x 4cm abrasion on the right face,
10.49 g of the composition of Example 296 was stuck. The composition
Items were applied daily and changed once a day. Crust formation on the second day
Epithelialization was observed without causing scarring on day 5.
Healed somehow. Test Example 21 (dry pruritus) 69-year-old man. Example for dry skin pruritus of both lower legs
50 g of the composition of No. 20 is applied and the food packaging
Covered with LUM (trade name Saran Wrap, manufactured by Asahi Kasei Corporation)
Finally, the itch disappeared. Test Example 22 (Pulmonary wound treatment test) A 65-year-old man. Vegetable state after hematoma removal surgery for intracerebral hemorrhage
And reaches the periosteum 15cm x 15cm in the sacrum IV
Depressed wounds occurred. Necrotic tissue adheres to the wound surface, deep poke
A pit was formed and exudate was also observed. In saline
Of the wound surface and povidone-iodine sugar application
Treatment, but had little effect. Real
30 g of the composition of Example 297 is filled in a pocket once a day.
And apply it so that it swells on the wound surface.
0cm x 30cm film dressing material (trade name
(Gadam, 3M). The composition and the film
Dressing was changed daily. On day 5 of administration of the composition
Necrotic tissue and exudate disappear from the wound surface and a rapid healing tendency
Indicated. At the same time, benign granulation increased. In the second month
Is markedly reduced in size and depth of the pressure sore,
Formed and pockets disappeared. Test Example 23 (Alveolar pyorrhea treatment test) 28-year-old female. Gingival swelling and redness are remarkable,
Had reached the top. Perform periodontal pocket scaling
30 g of the composition of Example 297 was applied once every two days
Inject into the ket and further cover the entire gum for 20 minutes
Applied. One month later, the swelling and redness of the gums almost disappeared
Turned off. Test Example 24 (Clip tear treatment test) 7-year-old woman. Lower lip bites with upper anterior teeth, leaving traces of teeth
He received a traumatic laceration. 5 g of the composition of Example 297
When applied for 0 minutes, it recovers to almost no scar
did. Test Example 25 (Dental Ulcer Treatment Test) 67-year-old woman. After denture wearing, denture incompatible with denture base mucosa
An ulcer with pain was caused by the pain. Detach and remove the denture
To cut dentures, fit dentures, and apply to ulcers
5 g of the composition of Example 297 were applied and the denture was refitted. 5
On examination after day, the ulcer had disappeared. Test Example 26 (Test for freckles) 38-year-old woman. Various cosmetics used for many years with freckles
Was not effective, the composition 2 of Example 298 was used.
6.2 g once a day for 20 minutes applied all over the face every day
By the 3rd day, the freckles are so thin that the moles stand out
It's gone. Test Example 27 (Stomatitis treatment test) A 43-year-old man. For painful stomatitis in the right palate
Then, 3 g of the composition of Example 170 was applied for 20 minutes.
Of course, the pain disappeared immediately. Test Example 28 (impetigo treatment test) 4-year-old woman. Composition of Example 297 for impetigo on the right upper arm
10 g once a day for 20 minutes, then fusidic acid
Sodium ointment (trade name: Fucidin Leo Ointment, Sankyo Co., Ltd.)
5 days after daily treatment with the appropriate amount applied
Healed without scars. Test Example 29 (Acne Vulgaris Treatment Test) 28-year-old woman. Various external treatments for acne vulgaris on the entire face
He tried steroidal anti-inflammatory drugs and oral antibiotics,
It was totally invalid. 30 g of the composition of Example 297 for 1 day
When applied once daily for 30 minutes, papules are flat in 2 months
It became tan, leaving only a slight redness. Test Example 30 (Skin Ulcer Treatment Test) 63-year-old woman. 1 cm diameter skin ulcer due to varicose veins
15 g of the composition of Example 297 was applied to the spot-like erosion.
Once applied daily for 20 minutes, erosion once
It disappeared and healed by eye application. Skin ulcer was also noticeable on the 10th day
The administration of the composition was stopped because
Formed a crust and healed. Test Example 31 (Cold sensation, itching, numbness treatment test) 71-year-old man. Cold sensation, pruritus,
Against numbness, apply 30 g of the composition of Example 31 once a week for 2 times.
When applied to the lower limb for 0 minutes, these symptoms were applied 7 times.
The state disappeared. Test Example 32 (Gingivitis treatment test) A 42-year-old man. Severe swelling and redness with severe toothache
For gingivitis, apply 10 g of the composition of Example 297 once for 10 times.
Minutes, three times on the first day and two times on the second day. 1 toothache
It disappears on the second application, and swelling and redness of the gums are markedly improved.
Was. Test Example 33 (Regrowth control test after hair removal) 38-year-old woman. I was shaving my armpit hair with a razor twice a week,
I was worried that I could reduce the number of shave with a razor. Implementation
30 g of the composition of Example 135 under the armpits, 15 g each, for 1 day
Apply once daily for 15 minutes.
Once the hair has been shaved once, the subsequent recurring hair is delayed and
I only needed to shave once with a razor. Example 300 Hydroxypropylcellulose 4 g in 200 ml of water, C
MC-Na (10 g) and sodium hydrogen carbonate (2.4 g) were added.
The solid content is completely dispersed or dissolved with a hand mixer.
And mix until light yellow, very viscous basic composition 2
16.4 g were obtained. Weigh out 25g and add citric acid
Add 0.24 g, mix and stir until completely dissolved.
Cream-colored carbon dioxide transdermal and transmucosal containing air bubbles
25.24 g of a composition for absorption was obtained. Example 301 Hydroxypropyl methylcellulose 4 in 200 ml of water
g, CMC-Na 6 g, sodium bicarbonate 2.4 g,
Carboxymethyl starch sodium 5g, methyl para
0.2 g of ben, 0.5 g of tocopherol acetate, geranium
Extract 0.1 g, rosewood extract 0.1 g, gray
Add 0.1 g of soup fruit extract and use a hand mixer
Stir until the solids are completely dispersed or dissolved, and light brown
218.4 g of a very viscous basic composition of color were obtained. So
Weigh 25g, add citric acid 0.24g and complete
Mix and stir until dissolved in
Composition for transdermal and transmucosal absorption of muted carbon dioxide 25.24
g was obtained. Example 302 Hydroxypropyl methylcellulose 4 in 200 ml of water
g, 8 g of CMC-Na, 2.4 g of sodium hydrogen carbonate,
0.2 g of methyl paraben, 1 g of tocopherol acetate,
Ranium extract 0.1 g, rosewood extract 0.1
g, grapefruit extract 0.1 g, copper chlorophylli
Add a trace amount of sodium and complete the solid content with a hand mixer.
Stir until completely dispersed or dissolved, and turn to a very viscous green
215.9 g of a dense basic composition were obtained. Weigh 25g
Remove and add 1.2 g of citric acid-coated sucrose granules to give granules
Mix and stir until completely dissolved.
26.2 g of green carbon dioxide transdermal / transmucosal composition
I got Example 303 4 g of carboxyvinyl polymer in 200 ml of water, CMC
-Na 10 g, sodium bicarbonate 2.4 g, methylpa
Raven 0.2g, Tocopherol acetate 0.5g, Zelani
Um extract 0.1 g, rosewood extract 0.1 g, g
0.1 g of rape fruit extract, copper chlorophyllin nato
Add a trace amount of Li and completely separate the solids with a hand mixer.
Stir until dispersed or melted, green very viscous salt
217.4 g of a base composition was obtained. Weigh out 25g
Add 0.2 g of lactic acid and mix until crystals are completely dissolved
Stir, light green carbon dioxide transdermal
25.2 g of a composition for transmucosal absorption was obtained. Example 304 4 g of carboxyvinyl polymer in 200 ml of water, CMC
-Na 8 g, sodium bicarbonate 2.4 g, methyl para
0.2 g of Ben, 1 g of tocopherol acetate, sicon extract
0.5 g, rosemary extract 0.1 g, perilla extract
0.1 g, Saw whisker extract 0.1 g, carrot extract
Add 0.1g and stirrer to completely disperse solids.
Or a viscous basic group until it dissolves.
216.5 g of the product were obtained. Weigh out 25g and use lactic acid
Add 0.2 g and stir until crystals are completely dissolved,
Transdermal / viscous thin carbon dioxide containing a lot of air bubbles
25.2 g of a composition for membrane absorption was obtained. Example 305 4 g of carboxyvinyl polymer in 200 ml of water, CMC
-Na 8 g, sodium bicarbonate 2.4 g, methyl para
0.2 g of Ben, 1 g of tocopherol acetate, sicon extract
0.1 g, turmeric extract 0.1 g, rosemary extract
0.1 g, perilla extract 0.1 g, soybean extract 0.
Add 1 g of carrot extract and 0.1 g of carrot extract, and fix with a stirrer.
Stir until the form is completely dispersed or dissolved.
216.5 g of a di-colored, very viscous basic composition were obtained.
25 g of the solution is weighed, and 0.2 g of lactic acid is added to complete the crystal.
Mix and stir until completely dissolved.
Persimmon carbon dioxide transdermal / transmucosal composition 25.2
g was obtained. Example 306 Carboxyvinyl polymer 6 g hydrogen carbonate in 200 ml of water
2.4 g sodium, 0.2 g methyl paraben, evening primrose
0.1 g of oil, 0.1 g of sicon extract, rosemary extract
Liquid 0.1g, perilla extract 0.1g, soybean extract
0.1 g, carrot extract 0.1 g, copper chlorophyllin
Add a small amount of sodium and stirrer to completely separate solids.
Stir until disperse or melt until pale green
In this way, 209.2 g of a viscous basic composition was obtained. 25g
Weigh and add 0.2 g of lactic acid to completely dissolve the crystals
Mix and stir until a metallic glossy paper containing a lot of air bubbles
GREEN CO2 transdermal and transmucosal composition 2
6.2 g were obtained. Example 307 Hydroxypropyl methylcellulose 30 in 10 kg of water
0 g, CMC-Na 500 g, sodium hydrogen carbonate 12
0 g, evening primrose oil 5 g, perilla extract 5 g, radish extract 5
g, carrot extract 5 g, rosemary extract 5 g,
5 g of Sprout extract, 0.5% copper chlorophyllin sodium
Aqueous solution 8g, natural vitamin E oil 10g, phenoxy
Add 100g of ethanol and stirrer to complete solid content
Stir until dissolved or dissolved in dark green
11.063 kg of a very viscous basic composition was obtained. So
Weigh 25 g of citric acid-coated sucrose granules 1.2 g
And mix until the granules are completely dissolved.
Light green carbon dioxide transdermal and transmucosal absorption of foam
26.2 g of an excipient composition were obtained. Example 308 Hydroxypropyl cellulose 300 in 10.5 kg of water
g, CMC-Na 500 g, sodium bicarbonate 120
g, evening primrose oil 5 g, perilla extract 5 g, siconium extract 5
g, carrot extract 5 g, rosemary extract 5 g,
5 g of Sprout extract, 0.5% copper chlorophyllin sodium
Aqueous solution 8g, natural vitamin E oil 10g, phenoxy
Add 100g of ethanol and stirrer to complete solid content
Stir until dissolved or dissolved in dark green
11.563 kg of a very viscous basic composition were obtained. So
Weigh 25 g of citric acid-coated sucrose granules 1.2 g
And mix until the granules are completely dissolved.
Light green carbon dioxide transdermal and transmucosal absorption of foam
26.2 g of an excipient composition were obtained. Example 309 2 g of sodium hydrogen carbonate and alginic acid N in 200 ml of water
a6g, CMC-Na8g, 1,3-butyleneglycol
2 g and a small amount of sodium copper chlorophyllin
Stir until solids are completely dispersed or dissolved
To obtain 218 g of a dark green, very viscous basic composition.
Was. Weigh out 25g and citrate coated sucrose granules
Add 1.2 g, mix and stir until the granules are completely dissolved,
Pale green carbon dioxide transdermal containing many air bubbles
26.2 g of a composition for transmucosal absorption was obtained. Example 310 2 g of sodium hydrogencarbonate in 200 ml of water, carmellose
Sodium 6g, CMC-Na8g, propylene glyco
2 g of dl-α-tocopherol 1 g of copper chlorophyll
Add a small amount of acetic acid sodium and complete the solid content with a stirrer.
Stir until completely dispersed or dissolved, very dark green
219 g of a viscous basic composition were obtained. Weigh 25g
Take and add 1.2 g of citric acid-coated sucrose granules to make the granules
Mix and stir until completely dissolved.
Composition 2 of Legreen for transdermal and transmucosal absorption of carbon dioxide
6.2 g were obtained. Example 311 2 g of sodium bicarbonate in 200 ml of water,
8 g of chill starch sodium, 8 g of CMC-Na, 1,
3-butylene glycol 2 g, phenoxyethanol 2
g, polyoxyethylene alkyl ether sodium sulfate
1 g, dl-α-tocopherol 1 g, copper chlorophyll
Add a trace amount of phosphorus sodium and stirrer to complete solids
Stir until dispersed or dissolved, very viscous green
224 g of a basic composition was obtained. Weigh out 25g
Add 0.2 g of lactic acid and mix until crystals are completely dissolved
Stirring, pale green carbon dioxide with lots of air bubbles
20.2 g of a composition for elemental transdermal / transmucosal absorption was obtained. Example 312 2 g of sodium hydrogencarbonate in 200 ml of water,
Lolidone 6g, CMC-Na8g, phenoxyethanol
2 g and octyldodecyl oleate 4 g were added.
Stir until solids are completely dispersed or dissolved
And 222 g of a creamy, very viscous basic composition.
Obtained. Weigh out 25g and citrate coated sucrose granules
Add 1.2 g, mix and stir until the granules are completely dissolved,
White cream-colored carbon dioxide containing many air bubbles
26.2 g of a composition for transdermal / transmucosal absorption was obtained. Example 313 200 g of water, 2 g of sodium bicarbonate,
6 g of propyl methylcellulose, 8 g of CMC-Na,
Serine 3g, phenoxyethanol 2g, evening primrose oil 0.
1 g, perilla extract 0.1 g, konkon extract 0.1 g, d
0.1 g of carrot extract, 0.1 g of rosemary extract,
0.1 g of Sawberry extract, 0.5 of natural vitamin E oil
g, a trace amount of sodium copper chlorophyllin,
-Stir until the solids are completely dispersed or dissolved,
222.1 g of a green, very viscous basic composition were obtained.
25 g of the solution is weighed, and 0.2 g of lactic acid is added to complete the crystal.
Mix and stir until completely dissolved, pail containing a lot of air bubbles
25. Green carbon dioxide transdermal / transmucosal absorption composition
2 g were obtained. Example 314 Add 10 g of sodium bicarbonate to 399.75 g of water
Polyoxyethylene melted and separately heat-melted at 40 ° C
2.5 g of rennonyl phenyl ether and natural vitamin E
Oil 1.25 g, phenoxyethanol 5 g, evening primrose oil
Add 0.25 g of the mixture and stir with stirring
0.25 g of perilla extract, 0.25 g of corn extract,
0.25 g of carrot extract, 0.2 of rosemary extract
5 g and 0.25 g of Soh arbor extract were added and stirred.
Add 50g of 1,3-butylene glycol in advance
15g of hydroxyethyl cellulose dispersed in
And a mixture of 15 g of CMC-Na was gradually added, and a stirrer was added.
-Stir until the solids are completely dispersed or dissolved,
500 g of a light brown, very viscous basic composition were obtained. So
Weigh 25 g of citric acid-coated sucrose granules 1.2 g
And mix until the granules are completely dissolved.
Slightly yellowish carbon dioxide containing foam Transdermal / transmucosal absorption
26.2 g of an excipient composition were obtained. Example 315 2 g of sodium hydrogencarbonate was added to and dissolved in 78.95 g of water
And polyoxyethylene which has been separately melted at 40 ° C
Nonylphenyl ether 0.5g and natural vitamin E oil
0.25 g, phenoxyethanol 1 g, evening primrose oil 0.
Add 05g of the mixture and stir with stirring
Perilla extract 0.05 g, Sicon extract 0.05 g, Nin
Gin extract 0.05 g, rosemary extract 0.05
g and 0.05 g of Saw squirt extract were added and stirred. This
Beforehand with 10 g of 1,3-butylene glycol
4 g of dispersed polyvinyl alcohol and CMC-
The mixture of Na3g was gradually added, and the solid content was
Stir until completely dispersed or dissolved.
To obtain 100 g of a viscous basic composition. Weigh 25g
Remove and add 1.2 g of citric acid-coated sucrose granules to give granules
Mix and stir until completely dissolved.
And yellowish carbon dioxide transdermal / transmucosal composition 2
6.2 g were obtained. Example 316 27.9 g of sodium hydrogencarbonate was added to 79.95 g of water and dissolved
And polyoxyethylene which has been separately melted at 40 ° C
Nonylphenyl ether 0.5g and natural vitamin E oil
0.25 g, phenoxyethanol 1 g, evening primrose oil 0.
Add 05g of the mixture and stir with stirring
Perilla extract 0.05 g, Sicon extract 0.05 g, Nin
Gin extract 0.05 g, rosemary extract 0.05
g and 0.05 g of Saw squirt extract were added and stirred. This
Beforehand with 10 g of 1,3-butylene glycol
4g of dispersed alginate Na and CMC-Na2
g of the mixture is added gradually, and the solid content is completely
Stir until dispersed or dissolved, light brown, very viscous
100 g of a basic composition was obtained. Weigh out 25g
Then, 1.2 g of citric acid-coated sucrose granules were added to complete the granules.
Mix and stir until completely dissolved, slightly yellow with lots of air bubbles
Composition for transdermal and transmucosal absorption of colored carbon dioxide 26.
2 g were obtained. Example 317 2 g of sodium bicarbonate was added to 79.95 g of water and dissolved
And polyoxyethylene which has been separately melted at 40 ° C
0.5g of polyoxypropylene alkyl ether and natural
0.25 g of vitamin E oil, 1 g of phenoxyethanol,
Add a mixture of 0.05 g of evening primrose oil and stir with a stirrer
Then, 0.05 g of perilla extract and 0.1 g of perilla extract were added.
05g, carrot extract 0.05g, rosemary extract
Solution, and 0.05 g of Soh-makuhi extract,
Stirred. Add 10g of 1,3-butylene in advance
6 g of sodium alginate dispersed by recall gradually
In addition, the solid content is completely dispersed or dissolved with a stirrer.
And mix until light brown, very viscous basic composition 1
00 g were obtained. Weigh out 25g and 0.2g of lactic acid
In addition, mix and stir until the crystals are completely dissolved,
Transdermal and transmucosal absorption of slightly yellowish carbon dioxide containing
25.2 g of the composition for use was obtained. Example 318 2g of sodium bicarbonate was added to 169.9g of water and dissolved.
And polyoxyethylene which has been separately melted at 40 ° C
2g of polyoxypropylene alkyl ether and natural bita
Min E oil 0.5g, phenoxyethanol 1g, evening primrose
Add a mixture of 0.1 g of oil and stir with a stirrer
Furthermore, perilla extract 0.1 g, radish extract 0.1 g, nin
0.1 g of gin extract, 0.1 g of rosemary extract,
0.1 g of a sperm extract was added and stirred. This
Disperse with 14 g of 1,3-butylene glycol
10 g of hydroxypropyl cellulose
In addition, the solid content is completely dispersed or dissolved by the stirrer.
And mix until the light brown very viscous basic composition 20
0 g was obtained. Weigh 25 g and add 0.2 g of lactic acid.
Mix and stir until the crystals are completely dissolved,
Contains slightly yellowish carbon dioxide for transdermal and transmucosal absorption
25.2 g of the composition were obtained. Example 319 Dissolved by adding 2 g of sodium bicarbonate to 171.9 g of water
And polyoxyethylene nonyl phenyl ether
2 g and natural vitamin E oil 0.5 g, phenoxyethanol
And a mixture of 1 g of evening primrose oil and a stirrer.
0.1 g of perilla extract and corn extract
0.1 g, carrot extract 0.1 g, rosemary extract
Add 0.1 g of the liquid and 0.1 g of the Soh Miao extract and stir.
Was. Add 14g of propylene glycol
Disperse 10 g of hydroxyethyl cellulose
Add slowly, and stirrer to completely disperse solids, or
Stir until dissolved, light brown, very viscous basic composition
200 g of the product were obtained. Weigh out 25g and add citric acid
Add 1.2 g of white sugar granules until the granules are completely dissolved
Mix and stir, slightly yellowish diacid containing lots of air bubbles
26.2 g of a composition for carbonized percutaneous / transmucosal absorption was obtained. Example 320 4 g of sodium hydrogen carbonate and 1,2-pentane in 167 g of water
Mixed solution of 6 g of diol and 1 g of phenoxyethanol 7
g was added and dissolved. 0.1 g of perilla extract
Extract 0.1 g, carrot extract 0.1 g, rosemary
-Add 0.1 g of extract and 0.1 g of Sohakuhi extract
Stirred. Add 16g of propylene glyco
4g of carboxyvinyl polymer dispersed
And 25 g of a dispersion liquid of 5 g of CMC-Na were gradually added.
Stir until solids are fully dispersed or dissolved
And add 0.5 g of orange oil and stir further to make it whitish
Obtaining 200 g of a very viscous basic composition of orange color
Was. Weigh out 25g and add 0.2g of lactic acid to crystal
Mix and stir until completely dissolved.
And orange-colored carbon dioxide transdermal / transmucosal absorption set
25.2 g of the product were obtained. Example 321 Dissolve 200 g of sodium bicarbonate in 9165 g of water,
300 g of 1,2-pentanediol prepared separately
And phenoxyethanol 40g, natural vitamin E oil 25
g of the mixed solution was added, followed by stirring and mixing. Prepare it separately
800g of 1,3-butylene glycol and polyvinyl
Dispersion of 200 g of rupyrrolidone and 250 g of CMC-Na
Slowly, and stirrer to fully disperse the solids.
Stir until dissolved, 5 g of perilla extract, radish extract
5 g, Sohakuhi extract 5 g, Rosemary extract 5 g
And mix with stirring.
10 kg of the composition were obtained. Weigh out 25g and asco
Add 0.2 g of rubic acid and mix until crystals are completely dissolved
Stir, whitish carbon dioxide transdermal
25.2 g of a composition for transmucosal absorption was obtained. Example 322 Dissolve 4 g of sodium bicarbonate in 163.6 g of water, and add
Polyoxyethylene lauryl ether
Add a mixture of 6 g and 1 g of phenoxyethanol and stir
Mixed. 0.1 g of perilla extract
0.1 g, Saw balm extract 0.1 g, rosemary extraction
Add 0.1 g of effluent, mix with stirring, and prepare separately.
Glycerin 16g and hydroxyethyl cellulose 4
g, and a dispersion of CMC-Na (5 g) was gradually added.
-Stir until the solids are fully dispersed or dissolved,
0.5 g of orange oil and a trace amount of copper chlorophyllin sodium
, And further agitate to make the pale green very viscous salt.
200 g of the basic composition was obtained. Weigh the 25 g and
Add 0.2 g of scorbic acid until the granules are completely dissolved
Mix and stir, whitish light green diacid containing lots of air bubbles
25.2 g of a composition for carbonized percutaneous / transmucosal absorption was obtained. Example 323 In a 500 ml beaker, 167.6 g of water was stirred in four blades.
About 120 times a minute with a stirrer equipped with a stirring rod
Sorbitan monos prepared separately while rotating
A mixture of 6 g of tearate and 1 g of phenoxyethanol
In addition, the mixture was stirred and mixed. Add 0.1 g of perilla extract to this
Extract 0.1g, Sohakuhi extract 0.1g, rose
0.1 g of Marie extract was added and mixed with stirring. Star
Remove the stir bar from the stirrer, and then push the stir bar into the beaker.
Break and cover with beaker with paraffin film
And poke paraffin film on the two ends of the beaker.
Insert two silicon tubes into one
Connect a small carbon dioxide cylinder to
Carbon was flushed. Five minutes later, the separately prepared propyle
Glycol 16g and hydroxypropylcellulose 4
g, needleless syringe containing a dispersion of 5 g of CMC-Na
Into the beaker-covered paraffin film.
, Gradually adding the dispersion while flowing carbon dioxide,
Until the solid content is sufficiently dispersed or dissolved with a stirrer
Stir, light yellow, very viscous with very many bubbles
200 g of a composition for transdermal and transmucosal absorption of carbon dioxide
Was. Example 324 Dissolved by adding 2 g of sodium bicarbonate to 171.9 g of water
2 g of acyl glutamate and dl-α-acetic acid
0.5 g of coferol, 1 g of phenoxyethanol, month
Add a mixture of 0.1 g of primrose oil and stir with a stirrer.
Furthermore, 0.1 g of turmeric extract, 0.1 g of turmeric extract
g, Cucumber extract 0.1 g, Rosewood extract
0.1 g and 0.1 g of Hamamelis extract were added and stirred.
Was. Add 14g of propylene glycol
10 g of dispersed hydroxypropylcellulose
Gradually, and the solid content is completely dispersed with a stirrer.
Stir until dissolved, light brown, very viscous basic
200 g of the product were obtained. Weigh out 25g and add citric acid
Add 1.2 g of coated sucrose granules until the granules are completely dissolved.
Mix and stir with a slightly yellowish two containing a lot of air bubbles.
26.2 g of a composition for transdermal / mucosal absorption of carbon oxide was obtained. Example 325 2 g of lactic acid was added to and dissolved in 169.9 g of water.
Heat-melted polyoxyethylene polyoxypro
Pyrene alkyl ether 2g and natural vitamin E oil 0.5
g, phenoxyethanol 1g, evening primrose oil 0.1g
Add the mixture and stir with a stirrer to further extract the perilla
0.1 g, sicon extract 0.1 g, carrot extract 0.
1 g, rosemary extract 0.1 g, soybean extract
0.1 g was added and stirred. 14g of this
Hydrogen dispersed in 1,3-butylene glycol
Gradually add 10 g of xypropylcellulose and stirrer
-Stir until the solids are completely dispersed or dissolved,
200 g of a light brown very viscous acidic composition were obtained. That
Weigh 25 g, add 1 g of sodium bicarbonate and powder
Mix and stir until the powder is completely dissolved, containing a large amount of air bubbles
Slightly yellowish carbon dioxide transdermal and transmucosal composition
26 g were obtained. Example 326 2 g of sodium hydrogen carbonate and alginic acid N in 200 ml of water
a6g and CMC-Na8g were added, and the solid content was
Stir until completely dispersed or dissolved, very viscous
214 g of a basic composition were obtained. Weigh out 25g
Then, 1.2 g of citric acid-coated sucrose granules were added to complete the granules.
Mix and stir until completely dissolved, yellowish white with lots of air bubbles
26.2 g of a composition for transdermal / transmucosal absorption of carbon dioxide
Was. Example 327 2 g of lactic acid and 10 g of sodium alginate were added to 200 ml of water.
Eh, the solid content is completely dispersed or dissolved by the stirrer
To give 212 g of a very viscous acidic composition.
Weigh 25 g and add 1 g of sodium bicarbonate
And mix until the granules are completely dissolved.
Light yellow carbon dioxide composition for transdermal and transmucosal absorption 26
g was obtained. <Production of citric acid-coated sucrose granules>
1.8 kg of acid 722 g of 7% HPC-L ethanol solution
Purified white solution using CF granulator
9 kg of sugar granules are sprayed and dried, then citric acid-coated white sugar
10.8 kg of granules were obtained. Test Example 34 (body of composition for carbon dioxide transdermal / transmucosal absorption)
Product increase rate evaluation test) Basic composition in transparent cup 5.5cm in diameter and 7cm in height
25g and citric acid coated sucrose granules 1.2g or acidic
25 g of the composition and 1 g of sodium bicarbonate are added and the volume A
Is measured. Stir 60 times, once a second, and stir
One hour after completion, the volume B is measured. Volume for volume A
The increase rate V of B is expressed in%, and the volume increase of the composition is based on the following criteria.
Evaluate additivity. V> 7 ++ 7>V> 5 ++ 5>V> 3 + 3> V0 The results are shown below.

[0127] Test Example 35 (Evaluation test of fluidity of composition) 1) Fluidity of basic or acidic composition The basic or acidic composition used in the kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide of the present invention is as follows. At the end of a glass plate with a smooth surface and a length of 40 cm, 1 g of
cm, and when the disc is moved at an angle of 60 degrees with respect to a horizontal plane so that the disc is on the top, the moving distance of the disc of the composition within 5 cm after 5 seconds is carbon dioxide. When it is reacted with a development aid to form a carbon dioxide transdermal / transmucosal absorption composition, it can be used as it is applied to the skin and mucous membranes. If the position is 15 cm or more and less than 30 cm, when the composition for transdermal and transmucosal absorption of carbon dioxide is reacted with a carbon dioxide generation aid and applied as it is, it is easy to flow off from the application site as it is. By impregnating the absorbent with a composition or a sponge, and applying the surface of the absorbent wet with the composition to the skin and mucous membranes, the above-mentioned medical effect or cosmetic effect can be obtained. Examples 180 to 266, 300
322 and 324 and Examples 180-2
In this test, all the acidic compositions Nos. 66, 325, and 327 had a moving distance of 15 cm or less in the test, and were reacted with a carbon dioxide generation auxiliary to form a composition for transdermal and transmucosal absorption of carbon dioxide. It could be applied to the skin and mucous membrane as it was. 2) Fluidity of carbon dioxide transdermal / transmucosal absorption composition The carbon dioxide transdermal / transmucosal absorption composition used in the present invention is:
On the edge of a 40 cm long glass plate with a smooth surface,
g is applied in the form of a disk having a diameter of 1 cm, and when the disk is set up at an angle of 60 degrees with respect to the horizontal plane so that the disk is on the top, the moving distance of the disk of the composition within 5 cm after 5 seconds is as follows. It can be applied as it is to the skin and mucous membranes. If the position is 15 cm or more and less than 30 cm, it is easy to flow off from the application site if applied as it is, so impregnate the absorbent such as cloth or sponge, and apply the surface where the absorbent is wet with the composition to the skin and mucous membrane The medical effect or beauty effect already described can be obtained.

Examples 1-249, 297 used in this test
All of the compositions No. to No. 327 had a moving distance of 15 cm or less, and could be used as they were applied to the skin and mucous membranes. Test Example 36 (Skin rejuvenation test) The transdermal carbon dioxide of Example 302 was applied to the right cheek of a 33-year-old woman.
The transmucosal composition 26.2 g was packed once a day for 15 minutes once a day for one month. One month after the start of the test, a 20 × magnifying lens was attached to a videoscope, and enlarged photographs of both cheeks of the woman were taken. 4 as control
A photo of the right cheek of an old girl was also taken. A dermatologist observed these photographs and found that the 33-year-old woman's right cheek photograph showed a skin groove pattern very similar to that of a 4-year-old girl's right cheek, and that the skin was dull and youthful. Assessed that there is. On the other hand, the photograph of the left cheek was judged to show a skin pattern in which a typical female in her thirties lost the freshness, and the composition for carbon dioxide transdermal / transmucosal absorption of the present invention had a skin rejuvenating effect. Was evaluated. Test Example 37 (Partial skin thinning test) The transdermal carbon dioxide of Example 309 was applied to the right cheek of a 29-year-old woman.
26.2 g of the composition for transmucosal absorption was applied once a day for 20 minutes, and this was continued for one month. Take a photo of the woman's face from the front twice on the day before the test and the day after the end of the test, read the image into the computer with a scanner, correct the scale of the photo, and correct the inclination of the face at the time of shooting, and check the change in the width of the face. As a result of the measurement, it became clear that the cheek to which the composition for transdermal / transmucosal absorption of carbon dioxide of the present invention was applied decreased the width of the face by 10.9%. It was also confirmed that the cheeks coated with the composition for transdermal and transmucosal absorption of carbon dioxide of the present invention turned white due to the whitening effect. Although the woman declared that she had gained 1 kg during the test period, the cheek on the side where the composition was not applied increased by 15.2% in proportion to the width of the face. Test Example 38 (Hand Whitening Effect Test) The composition for transdermal and transmucosal absorption of carbon dioxide of Example 307 was applied to the entire back of the right hand of a 33-year-old woman. 5
After a minute, the composition was removed with a tissue paper, rinsed thoroughly with water, wiped with a towel and compared with the left hand. The right hand clearly had a white, transparent skin.
This whitening effect persisted the next morning. Test Example 39 (Skin ulcer treatment test) A composition for transdermal and transmucosal absorption of carbon dioxide in Example 327 for a skin ulcer formed on the outside of the right lower leg of a 53-year-old man with a major axis of 4 cm, a minor axis of 2.5 cm and a depth of 4 mm When 10 g of the product was applied, the formation of granulation was started the next day. The same treatment was performed twice a week. Granulation was completed in 2 weeks, epithelialization was completed in 3 weeks, and the skin ulcer was healed. Test Example 40 (Oxygen Saturation Measurement Test in Tissue) One hour after foaming, insert the right index finger into the composition of the present invention described in Example 1 and soak for 5 minutes. The index finger was inserted to measure the oxygen saturation in the tissue.

A similar experiment was carried out using a carbonated beverage (trade name: Coca-Cola, Coca-Cola Japan) instead of the composition of the present invention of Example 1, but no change was observed in the oxygen saturation in the tissue.

Changes in Tissue Oxygen Saturation Sp02 by Pulse Oximeter 31-year-old man 34-year-old woman 42-year-old man 57-year-old man 29-year-old woman 47-year-old woman 43-year-old man 97 96 96 95 97 96 98 before Example 99 99 99 99 99 99 99 99 Test Example 41 5 Minutes After Inserting the Index Finger into the Composition (Beautiful Skin / Whitening Test on the Back of the Hand) 26.2 g of the composition for transdermal and transmucosal absorption of carbon dioxide of Example 307 over the back of the right hand of a 33-year-old woman Apply 0.1 g of evening primrose oil, 0.1 g of siconium extract to the entire back of the left hand,
A mixture of 0.1 g of a rosemary extract, 0.1 g of a perilla extract, 0.1 g of a soybean extract, and 0.1 g of a carrot extract was applied. Five minutes later, the backs of both hands were washed with water until the application was completely removed, and the hands were wiped with a towel. When comparing the hands, the back of the right hand clearly became white and transparent, while the back of the left hand The skin became slightly smooth, and only a slight whitening effect was felt, and no transparency of the skin was observed. The whitening effect of the right hand back persisted the next morning. From these results, it was suggested that the composition of the present invention had a stronger skin and whitening effect than the application of the herbal extract. Test Example 42 (Beautiful skin / whitening test on the back of the hand) 26.2 g of the composition for transdermal and transmucosal absorption of carbon dioxide of Example 307 over the back of the right hand of a 33-year-old woman, and the composition of Example 326 over the back of the left hand 26.2 g were applied. Five minutes later, the backs of both hands were washed with water until the applied material was completely removed, the hands were wiped off with a towel, and the hands were compared. The backs of both hands became white and transparent compared to before the test. The back of the hand became more white and transparent. The whitening effect of both hands was maintained the next morning. Considering this result and the result of Test Example 41, the composition of the present invention has strong skin and whitening effect, and enhances the transdermal absorption efficiency of herbal extract,
It was suggested that it also has a synergistic effect with herbal extracts. Comparative Example 1 A mousse-like foamable composition containing water and nonionic polymer coagulant polyacrylamide, glycerin, vitamin E, and carbon dioxide (trade name: Skinless Jelly 1500, Okamoto, Okamoto) was prepared in Examples 1 to 84. <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption><Persistence of air bubbles>
The test was performed according to. However, since the mousse-like foamed composition has a very small volume-to-weight ratio, 8 g of the foamed composition was tested.
Was provided. The evaluation of the mousse foam composition according to <Evaluation Criteria 2> was 0. An attempt was made to carry out a tissue oxygen saturation measurement test using a pulse oximeter in accordance with Test Example 40. However, one hour after foaming, the foam of the mousse-like foamed composition almost disappeared, and the test could not be carried out. .

Continued on the front page F term (reference) 4C076 AA06 AA09 AA16 BB31 CC11 CC44 DD26 DD28G DD37 DD38 DD43 DD46 DD67 EE06G EE08G EE09 EE30G EE31G EE32G EE36G EE38G FF63 4C086 AA01 AA02 HA16 MA03 Z05A05 Z22

Claims (29)

[Claims] 1. A composition which comprises water, a thickener and foamed carbon dioxide, and is capable of continuously absorbing carbon dioxide transdermally and transmucosally. 2. 60 to 9 water based on the total amount of water and thickener.
The composition according to claim 1, comprising 9.9% by weight and 0.1 to 40% by weight of a thickener. 3. The composition according to claim 1, further comprising a humectant. 4. The composition according to claim 3, wherein the content of the humectant is 0.1 to 25% by weight. 5. The method according to claim 1, further comprising a lipophilic substance.
The composition according to any one of the above. 6. A lipophilic substance content of 0.01 to 10% by weight.
The composition according to claim 5, which is: 7. The method according to claim 1, further comprising a surfactant.
The composition according to any one of the above. 8. A surfactant content of 0.01 to 10% by weight.
The composition according to claim 7, which is: 9. The method according to claim 9, wherein the content of the foamed carbon dioxide is 0.1% by volume or more, preferably 1% by volume or more, more preferably 2% by volume or more.
9. The composition according to claim 1, further comprising at least 3% by volume, particularly preferably at least 4% by volume, most preferably at least 5% by volume.
The composition according to any one of the above. 10. The foamed carbon dioxide held in the composition in an amount of 40% by volume or more, preferably 60% by volume or more, more preferably 80% by volume or more in a bubble form for 5 minutes or more, preferably 30 minutes or more. The composition according to any one of claims 1 to 9, which can be held for more than 1 hour, more preferably for 2 hours or more. 11. A glass plate having a length of 40 cm having a smooth surface and 1 g of a 1 g diameter disk applied to the end of a glass plate having a smooth surface, and standing at an angle of 60 degrees with respect to a horizontal plane so that the disk comes on top. The composition according to any one of claims 1 to 10, wherein the moving distance of the disk after 5 seconds is within 30 cm, preferably within 25 cm, more preferably within 20 cm, especially within 15 cm. 12. A basic composition containing water, a thickener and a carbonate, and a carbon dioxide generation aid containing at least 10% or more of an acid based on the number of moles of the carbonate contained in the basic composition. Agent (I), which retains carbon dioxide generated in a composition obtained by mixing them at the time of use, and 40% by volume of carbon dioxide held in the composition at the maximum volume after foaming. Or more, preferably 60% by volume or more, more preferably 80% by volume or more in a bubble form for 5 minutes or more, preferably 30 minutes or more, more preferably for 1 hour or more, and particularly for 2 hours or more. -A kit for producing a composition for transmucosal absorption. 13. A basic composition comprising 60 to 99.8% by weight of water and 0.1% of a thickener based on the total amount of water, thickener and carbonate.
The kit according to claim 12, comprising 1 to 30% by weight and 0.1 to 10% by weight of a carbonate. 14. The volume increase rate when the basic composition and the carbon dioxide generation auxiliary agent (I) are mixed is 0.1% by volume or more of the total volume of the basic composition and the carbon dioxide generation auxiliary agent.
The kit according to claim 12 or 13, preferably at least 1% by volume, more preferably at least 3% by volume, particularly preferably at least 5% by volume, most preferably at least 7% by volume. 15. The kit according to claim 12, wherein the basic composition contains 0.1 to 25% by weight of a humectant. 16. The surfactant is added to the basic composition in an amount of 0.01-1.
The kit according to any one of claims 12 to 15, comprising 0% by weight. 17. A lipophilic substance of 0.01 to 1 in a basic composition.
The kit according to any one of claims 12 to 16, comprising 0% by weight. 18. When 1 g of a 1 cm diameter disk is applied to the end of a glass plate having a length of 40 cm and having a smooth surface, and the disk is placed at an angle of 60 degrees with respect to a horizontal plane so that the disk comes up. The composition for transdermal and transmucosal absorption of carbon dioxide according to any one of claims 12 to 17, wherein the moving distance of the disk after 5 seconds is within 30 cm, preferably within 25 cm, more preferably within 20 cm, especially within 15 cm. A composition produced from a product production kit. 19. An acidic composition containing water, a thickener and an acid, and a carbon dioxide generation auxiliary (II) containing at least 10% or more of a carbonate based on the number of moles of the acid contained in the acidic composition. ), Which retains carbon dioxide generated in the composition obtained by mixing them at the time of use, and is preferably 40% by volume or more of carbon dioxide retained in the composition at the maximum volume after foaming, preferably Is at least 60% by volume, more preferably 8%
A kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide which can hold 0% by volume or more in a bubble form for 5 minutes or more, preferably 30 minutes or more, more preferably 1 hour or more, especially 2 hours or more. 20. An acidic composition comprising 60 to 99.8% by weight of water and 0.1 to 3% by weight of a total amount of water, a thickener and an acid.
20% by weight and 0.1 to 10% by weight of an acid.
The kit according to 1. 21. An acidic composition and a carbon dioxide generation auxiliary (I)
The volume increase rate when mixing (I) is 0.1% by volume or more, preferably 1% by volume or more, more preferably 3% by volume of the total volume of the acidic composition and the carbon dioxide generation auxiliary (II).
Or more, particularly preferably 5% by volume or more, and most preferably 7% by volume.
The kit according to claim 19 or 20, which is at least volume%. 22. A humectant of 0.1 to 25% by weight in the acidic composition.
The kit according to any one of claims 19 to 21, comprising: 23. A surfactant of 0.01 to 10 in the acidic composition.
The kit according to any of claims 19 to 22, comprising wt%. 24. A lipophilic substance in an acidic composition of 0.01 to 10%.
The kit according to any one of claims 19 to 23, comprising wt%. 25. A glass plate having a length of 40 cm whose surface is smooth is coated with 1 g of a disk having a diameter of 1 cm in a disk shape, and the disk is placed at an angle of 60 degrees with respect to a horizontal plane so that the disk is on top. The distance of the disk of the composition after 5 seconds is 30 cm
Within, preferably within 25 cm, more preferably 20 c
A composition produced from the kit for producing a composition for transdermal and transmucosal absorption of carbon dioxide according to any one of claims 19 to 24, wherein the composition is within 15 m. 26. Itching associated with mucocutaneous mucosal disease or mucosal disorder, comprising the composition according to any one of claims 1 to 11 or the composition according to claim 18 or 25; Sensation, numbness; dental disease; mucocutaneous skin damage; purulent skin disease; dyskeratosis; musculoskeletal disease;
And a preventive or therapeutic agent for any disease selected from the group consisting of nervous system diseases. 27. The composition of any one of claims 1 to 11 or the composition of claim 18 or 25, which reduces or makes less noticeable spots and freckles, a whitening action,
Skin rejuvenation, skin tightening, partial obesity of face, legs, arms, abdomen, flank, back, neck, chin, etc. Cosmetics having the action of 28. The cosmetic according to claim 27, wherein the cosmetic is a cream, a pack, a gel, a paste or a mask. 29. Carbon dioxide, an acid, a thickener and water are contained in a state in which carbon dioxide is not substantially generated, and a mixture of carbonate, acid, thickener and water contains foamed carbon dioxide. A kit according to any one of the following (i) to (iv) capable of obtaining a composition for transdermal / transmucosal absorption of carbon dioxide: (i) a basic composition containing water, a thickener and a carbonate A kit comprising an acidic composition containing water, a thickener and an acid. (ii) A kit comprising a carbonate and a solid acid (granules, granules, powder), and a viscous composition comprising water and a thickener. (iii) A kit comprising a viscous composition comprising water and a thickener, and a composite granule (fine granules, powder) of a carbonate and an acid. (iv) A kit containing a carbonate, an acid, a thickener, and water.