JP2006008674A - Drug and plaster for suppressing allergic reaction - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a drug for suppressing allergic symptoms occurring in the eyes or nose. <P>SOLUTION: The drug containing a compound A1 or a precursor A0 and for suppressing an allergic reaction occurring in the eyes or nose down to 0-95% of the case without contact with the drug, by making the A1 or an A2 containing the precursor A0 of the compound A1 for suppressing the allergic reaction endermically permeate into the cells from the surface of the skin, by bringing them into contact with the outer surface of the eyelids when the allergic reaction occurs inside the lids of the eyes of a mammal, and by bringing the compound A1 or the medicine A2 containing the precursor A0 of the compound A1 for suppressing the allergic reaction into contact with the outer surface of the nose when the allergic reaction occurs inside the nose. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a drug for external use in medicine, and relates to a drug for suppressing specific allergic symptoms.

Pollen is a phenomenon in which pollen scatters and enters the body of animals and humans and develops allergic symptoms. Especially when the conjunctiva of the eye becomes itchy, it is very hard. The more you rub your eyelids, the more it becomes itchy. As a treatment for this, a method of taking a medicine containing an antiallergic agent and a method of putting an eyedrop containing an antiallergic agent into the eyes are performed. However, there are the following disadvantages. 1) Since eye drops are immediately washed away by tears, the effect does not last. 2) Pointing to eye drops many times a day is bad for the eyes. For example, it tends to cause cataracts and glaucoma. No blood vessels pass through the cornea or lens of the eye, and nutrients are supplied from tears. If foreign substances are injected there, it is not good for the eyes. 3) If you take the medicine, it will be effective for the whole body, so the movement of the body becomes dull and sleepy. In addition, many people get stomach upset with internal use. 4) Many people dislike injection because there is a shock to the body due to the whole amount of medicine entering the body in an instant. Accordingly, in order to prevent itching or itching from the eyes, there is a need for preferred drugs that are more durable and less harmful.
In addition, allergic symptoms may occur in the nasal cavity, and a lot of sneezing and runny nose may occur. Even if an antiallergic agent or vasoconstrictor is sprayed on the nasal cavity, it is often washed away by the runny nose and becomes ineffective. There is a need for a drug that effectively suppresses allergic symptoms that cause nosebleeds when sprayed too many times.
Antiallergic agents are toxic for side effects, so it is desirable to use them as little as possible. To do so, administer only the necessary amount to the necessary part. Development of a drug that meets this demand is desired.
A bansoko with a metal spring is stretched on the outer surface of the nose, and the surface is pulled outward to enlarge the nostril (nasal enlarged bansoko). However, this is only for the physical effect without a drug, and has no antiallergic effect.
Some cosmetics sometimes contain anti-allergic agents to prevent skin allergic reactions caused by cosmetics. Because cosmetics are mainly applied to the face, they are also applied to the eyelids. However, this is intended to suppress the skin allergic reaction caused by cosmetics, not to suppress the allergic reaction inside the eyelid caused by pollen, especially cedar pollen.
Pollen often occurs when pollen adheres to the mucous membrane in the eyes or nasal cavity and releases the antigen. For this reason, the symptom is likely to appear inside the eyes and nasal cavity.

  Provided is a drug that effectively suppresses itching of the eyes caused by pollen, preferably pollen allergic reaction, without causing eye damage. The present invention also provides a drug for continuously and effectively suppressing symptoms such as sneezing due to the allergic reaction in the nose, nasal mucus not stopping, and clogging of the nose.

(I) The present invention has been achieved by the following items.
(1) When an allergic reaction occurs inside the eyelid of a mammal, by contacting the outer surface of the eyelid with a drug A2 containing the compound A1 that suppresses the allergic reaction or its precursor A0, Alternatively, when an allergic reaction occurs inside the nose, by contacting the outer surface of the nose with a drug A2 containing the compound A1 that suppresses the allergic reaction or its precursor A0, A1 or A0 is removed from the surface. is transdermal penetration into the cell, the allergic reactions of the internal, 0-95 in the absence of said contacting, preferably 10 ^-4 to 70, more preferably 10 ^-3 to 30, more preferably 10 ^-3 to Drug that suppresses to 10%.
(2) The inside of the eyelid represents the shaded area of FIG. 1, and the outer surface of the eyelid is the shaded area of FIG. 2 (below the eyebrow line, 20 above the lower end of the eye, preferably above the line 15 mm below, 5 to 100, preferably 20 to 100, more preferably 50 to 100, and even more preferably 80 to 100% of the region 20 mm from both ends of the line (preferably inside the line 15 mm away) (1 ) Drug described.
(3) The inside of the nose refers to a portion between the inner surface of the nasal cavity and the outer surface of the nose, and the outer surface is a shaded portion in FIG. 3 (below the eyebrow line, 22 from the raised end of the nose) 5), preferably 20 to 100, more preferably 50 to 100, and still more preferably 80 to 100%.
(4) The nasal cavity refers to a cavity existing between the nostril entrance and the nasopharynx (or nasopharyngeal head), or a cavity through which air entered from the nostril entrance passes to reach the nasopharynx The medicine according to (3), characterized in that the nasal cavity also contains a paranasal sinus.

(5) The A1 or A0 is at least one of an antiallergic agent, a steroid agent, and an anti-inflammatory agent, and the A2 is an A1 of 10 ^{−3 to} 99, preferably 10 ^{−2 to} 90, more preferably 0. The drug according to (1), wherein the drug is contained in an amount of 1 to 50% by mass, and preferably A1 or A0 is at least one of an antiallergic agent and a steroid agent.
(6) The drug according to (1), wherein the A2 contains 0.1 to 99.999, preferably 1 to 99.9, more preferably 5 to 99% by mass of the dispersion medium A3.
(7) The medicine according to (1), wherein the mammal is a monkey, a dog, a cat, or a human, preferably a human.
(8) The contact of the drug A2 is further 0.1 to 100, preferably 1 of the total area of the nostril entrance area (refers to the nostril entrance and the intranasal area between 30 and preferably 20 mm from the nostril entrance). The agent according to (4), which is formed by adding to an area of ˜99, more preferably 10 to 90, still more preferably 30 to 80%.
(9) The A2 promotes the absorption rate of the A1 to the skin by 1.1 to 10 ⁵ , preferably 1.5 to 10 ⁴ , more preferably 2 to 10 ³ times. The drug according to (1), which is contained.
(10) The drug according to (1), wherein the allergic reaction is a reaction that causes allergic symptoms in a living body.
(11) The drug according to (1), wherein the allergic symptom is urticaria.
(12) The drug according to (11), wherein the urticaria is an itching reaction.
(13) The reaction is a reaction in which the tissue cells of the part are expanded 1.02 to 100, preferably 1.1 to 50, more preferably 1.3 to 20, and further preferably 1.6 to 10 times. The drug according to (1), characterized in that it has a certain feature.
(14) The cross-sectional area of the narrowest portion in the ventilation hole from the nostril entrance to the nasopharynx is the original 0 to 98, preferably 0 to 80, more preferably 0 to 20, still more preferably 0 to The medicine according to (13), characterized in that it indicates an aspect reduced to 5%.
(15) The itch is reduced to 0 to 95, preferably 0 to 70, more preferably 0 to 20, and further preferably 0 to 5% before contact due to the contact (12). ) Drug described.

(16) The cross-sectional area reduction amount is reduced to 0 to 95, preferably 0 to 70, more preferably 0 to 20, still more preferably 0 to 5% before contact due to the contact. And (14) the drug.
(17) Before the contact, 0.1 to 100, preferably 1 to 100, more preferably 10 to 100, and still more preferably 40 to 100% of the hair at the planned contact location is removed. The drug according to (1), which is characterized.
(18) 5 to 100, preferably 20 to 100, more preferably 50 to 100% of the total amount of percutaneous penetration of A1 or A0 does not pass through the stratum corneum of skin, and pores, sweat glands, sebaceous glands (B3) The drug according to (1), which has penetrated through.
(19) Prior to the contact, 5.0 to 100, preferably 30 to 100, more preferably 70 to 100% of deposits such as red, fat, and dust on the skin surface at the planned contact location are removed in advance. The drug according to (1), which is characterized by
(20) The drug according to (1), wherein the inside of the eyelid is a region including a conjunctival portion of the eye.
(21) The temperature of the outer surface of the eyelid or the outer surface of the nose and / or the drug A2 to be contacted is 0.5 to 50, preferably 1 to 40, more preferably 3 than the temperature when nothing is done. The drug according to (1), wherein the drug is increased by -30 ° C.
(22) The drug according to (21), wherein the temperature rise is performed by bringing a heated object into contact with the outer surface and / or drug A2, or by irradiating with a heat ray.
(23) First, raise the temperature of the outer surface by 0.5 to 50, preferably 1 to 40, more preferably 3 to 30 ° C., and then bring A2 into contact with the surface. Next, the drug according to (1), wherein the temperature of the skin surface is lowered by 0.5 to 50, preferably 1 to 40, more preferably 2 to 30 ° C.
(24) It is characterized in that 0.1 to 100, preferably 1 to 100, more preferably 10 to 100% of fat in B3 [sebaceous gland, sweat gland or pores] is released outside the body by the temperature rise of the outer surface. The drug according to (21) or (23).

(25) After the temperature rise, 1 to 100, preferably 10 to 100, more preferably 40 to 100% of sebum on the skin surface is removed, and then A2 is contacted (24). The drug described.
(26) The contacted drug A2 is sucked into the hole by the contraction action of B3 due to the temperature drop, and the suction depth is 10 ^{−3 to} 5, preferably 10 ^{−2 to 3} mm. (23) The drug according to (23).
(27) The drug according to (23), wherein the operation of temperature increase and subsequent temperature decrease is repeated 1 to 100, preferably 2 to 50 times.
(28) 0.01 to 4.99% of the total amount of percutaneous penetration of A1 or A0 permeates through B3 without passing through the stratum corneum of the skin (1) Drugs.
(29) The agent according to (1), wherein the hair loss rate at the planned contact place is 0 to 0.099 before the contact.
(30) The drug according to (1), wherein the pH of the A2 is 2 to 10, preferably 3 to 9.
(31) The contact is made in the order of (skin / layer for controlling diffusion amount of drug / layer of drug A2), the control layer is 1.1 to 10 ⁵ between both surfaces of the control layer, Preferably, the drug according to (1), which produces a concentration difference of A1 or A0 that is 1.5 to 10 ⁴ , more preferably 3 to 10 ³ times.
(32) The control layer is a porous film having 1 to ¹⁰ 10 pores per cm ² , preferably 3 to 10 ⁸ , more preferably 10 to 10 ⁶ pores through which A1 molecules can pass ( 31) The drug described.
(33) Described in (1) or (13), wherein the reaction inhibition refers to inhibiting expansion of the cells to 0 to 90, preferably 0 to 30, more preferably 0 to 5%. Drug.
(34) The contact of A2 is within the nasal cavity, and the ratio of (oral surface area / outer surface area) ratio is 1.1 to ∞, preferably 2 to ∞, more preferably 10 to ∞, The drug according to (8) or (106), which is preferably performed at 30 to ∞.
(35) The contact of A2 is also added to the surface of 1 to 100, preferably 10 to 90, more preferably 30 to 80% of the palatal surface (upper jaw inner surface, oral cavity ceiling surface) in the oral cavity. (4) The drug according to (4),
(36) The palate surface indicates a surface having an area of 50% on the face side of the inner surface of the upper jaw, and preferably indicates the inner surface existing in the fluoroscopic region of the face central region (2-2) in FIG. (35) The medicine according to (35).
(37) The contact is made with the drug described in any of (53) to (101), preferably the support is hydrophobic as described in (98) (8), ( 34) The drug according to any one of (35) and (36).

(51) The drug according to (1), wherein the A2 is a fluid non-solid drug, preferably an ointment, cream, lotion, liniment or spray.
(52) The drug according to (51), wherein the contact is made by applying the A2 on the outer surface.
(53) After the application, a cover (cover) covering 5 to 100, preferably 20 to 100, more preferably 60 to 100% of the application part is covered, and the surface on the side where the cover comes into contact with the skin is A6 (52) The chemical | medical agent characterized by the above-mentioned.
(54) The cover has a drying rate of 0 to 70, preferably 0 to 5, more preferably 10 ^{−10 to} 0.1% of one or all of the components of moisture or A2 as compared to the case without the cover. The drug according to (53), which is a mode of suppression.
(55) The drug according to (53), wherein the cover is a bendable substance, preferably a flexible sheet.
(56) The drug according to (53), wherein the cover is an inflexible substance.
(57) The cover is a sheet-like material composed of one or more of a woven fabric, a nonwoven fabric, a brushed fabric, a porous membrane, paper, a sheet, a film, and a metal foil, and preferably a film-like sheet material. The drug according to (55), which is characterized by
(58) The adhesive layer is present on an area of 0 to 100, preferably 1 to 100, more preferably 10 to 100, still more preferably 30 to 100% of the total area of the A6 ( 53) The drug described.
(59) The area of 0 to 100, preferably 1 to 100, more preferably 10 to 100, and still more preferably 30 to 100% of the total area of A6 is a surface that can be adhered to the outer surface. The medicine according to (53), characterized in that it is characterized.

(60) The drug according to (58) or (84), wherein the adhesive layer is a pressure-sensitive adhesive layer.
(61) The peripheral portion of at least 1 to 100, preferably 10 to 100, more preferably 30 to 100% of the total circumference of the A6 is a cover that can be bonded (53) or ( 59) The drug described.
(62) The ratio of (major axis length / minor axis length) of A6 of the sheet-like cover is 1 to 10 ⁴ , preferably 1.1 to 10 ³ , more preferably 1.3 to 100. The drug according to any one of (81) and (86) to (90), wherein at least peripheral portions on both sides in the major axis direction are surfaces that can be bonded.
(63) Description of (61) or (62), wherein the area ratio of the A6 surface that can be adhered is 1 to 90, preferably 2 to 50, more preferably 5 to 30% of the total area of A6. Drugs.
(64) The pad is present on a surface having an area of 0 to 100, more preferably 1 to 100, more preferably 5 to 97, and still more preferably 20 to 90% of the total area of A6 of the cover, However, it has open-type voids that can contain water or A2 or A3, such as woven fabrics, nonwoven fabrics, and sponges, and the volume ratio of the voids is 1 to 99.9, preferably 5 to 99, more preferably (20), wherein the drug is a material of 20 to 98, more preferably 40 to 95.
(65) The drug according to (64), wherein the pad has a thickness of 10 ⁻⁵ to 10, preferably 10 ^{−4 to} 5, more preferably 10 ^{−3 to 3} mm.
(66) The drug according to (64), wherein the pad is composed of one or more materials of woven fabric, non-woven fabric, carpet type (brush type), porous membrane, and sponge.
(67) In the aspect of the area of 0 to 100, preferably 1 to 100, more preferably 10 to 100, still more preferably 30 to 100% of the total area of the place other than the place where the bonding is possible, in A6. The drug according to (61) or (64), wherein a pad is present.
(68) The drug according to (64), wherein the pad is in an embodiment in which the pad is bonded and fixed onto an adhesive layer on a support.

(69) The cover or the pad portion contains 1 to 4 kinds of humectants, A1, A0, A2 and A3, and the total content is 10 ⁻¹⁰ to 10 per cm ² , preferably 10 ^{−8 to} 3 More preferably, it is 10 < ^-6 > -2g, The chemical | medical agent as described in (53) or (64) characterized by the above-mentioned.
(70) In the area of 0 to 100, preferably 1 to 100, more preferably 10 to 100, and still more preferably 50 to 100% of the total area of the place other than the place where the bonding is possible in A6, 1 to 4 kinds of A1, A0, A2 and A3 are contained, and the total content is 10 ⁻¹⁰ to 10, preferably 10 ^{−8 to} 3, more preferably 10 ^{−6 to 2} g per 1 cm ^2. The agent according to (59) or (61), characterized in that it is characterized.
(71) The cover or the pad part substantially does not contain 1 to 4 kinds of moisturizers, A1, A0, A2 and A3. Specifically, the total content is 0 to 10 ⁻⁶ per 1 cm ^2. The medicine according to (53) or (64), characterized by pointing to less than g.
(72) Including 1 to 4 kinds of humectants, A1, A0, A2 and A3 in the adhesive layer, the total content is 10 ^{−10 to} 90, preferably 10 ^{−8 to} 60, more preferably The drug according to (58), which is 10 ⁻⁶ to 40% by mass.
(73) The cover or the adhesive is in a mode that cannot be continuously adhered and fixed on the outer surface by itself. The drug according to (53) or (81), wherein the drug is fixed to the drug.
(74) The color of the outer surface (the surface opposite to the skin) of the cover is skin color, and when this is pasted on the outer surface, the contrast with the skin is preferably 0 to 3, more preferably 0 to 1. More preferably, it is 0-0.3, The chemical | medical agent of (53) description characterized by the above-mentioned.
(75) The outer surface of the cover (the non-adhering surface) is in a mode in which a treatment for reducing the regular reflectance to the original 10 ⁻³ to 70, preferably 0.01 to 20% is performed. The drug according to (53), which is characterized by
(76) The water content of the substance present on the cover or the support of the adhesive is from 0 to 99, preferably from 1 to 98, more preferably from 10 to 95, still more preferably from 25 to 90% by mass. The agent according to (53) or (81), which is characterized.

(81) The contact is made by bringing a surface having the A2 layer (A2 surface) into contact with the outer surface of the agglutinant having the A2 coating layer (A2 layer) on the support. The drug according to (1), which is characterized.
(82) The aspect of the support of the aforesaid adhesive satisfies one or more of the requirements of (54) to (57), (72), (73), (74) (81) The drug described.
(83) The area ratio of the A2 layer of the adhesive is 1 to 100, preferably 5 to 100, more preferably 30 to 100, still more preferably 60 to 100% of the total area of the (A2 surface). (81) The drug according to (81)
(84) The drug according to (83), wherein an undercoat layer is present between the support and the A2 layer in order to improve the adhesion.
(85) The drug according to (83), wherein the A2 layer is present in a state of being in direct contact with the support or in a state of being in contact with the undercoat layer.
(86) There is an adhesive layer on the (A2 surface) side on the support, and the area ratio thereof is 0 to 100, preferably 1 to 100, more preferably 10 of the total area of the (A2 surface). The drug according to (81), characterized in that it is -100, more preferably 50-100%.
(87) The agent according to (86), wherein the adhesive layer is placed after the A2 layer is placed on a support.
(88) The drug according to (86), wherein the adhesive layer is present in a state of being in direct contact with the support or in a state of being in contact with the undercoat layer.
(89) The medicine according to (86), wherein the A2 layer is placed after the adhesive layer is placed on a support.
(90) A peripheral portion of at least 1 to 100, preferably 10 to 100, more preferably 30 to 100% of the total circumference of the (A2 surface) is the surface that can be bonded (81) , (86) to (89)
(91) The ratio of (major axis length / minor axis length) of (A2 surface) is 1 to 10 ⁴ , preferably 1.1 to 10 ³ , more preferably 1.3 to 100, (81) The agent according to any one of (86) to (90), wherein the peripheral portions on both sides in the major axis direction are surfaces that can be bonded.

(92) The A2 layer is present on a surface having an area of 1 to 100, preferably 10 to 100, more preferably 40 to 100% of the total area of the (A2 surface) other than the place where adhesion is possible. (90) or (91) described above,
(93) On the surface having an area of 0 to 100, preferably 1 to 100, more preferably 10 to 100, and further preferably 30 to 100% of the total area other than the place where the (A2 surface) can be bonded, (64) to (66), the drug according to any one of (90) or (91), wherein the pad according to any one of (68) and (68) is present, and the pad portion contains A2.
(94) The amount of A1 or A0 present in the A2 layer or in the pad portion is 10 ^{−6 to} 90, preferably 10 ⁻⁴ to 30, and more preferably 10 ^{−3 to} 20 mass%. The drug according to any one of (81), (83), (92), and (93), which is characterized.
(95) The adhesive layer contains A1 or A0, and the content is 10 ^{−6 to} 90, preferably 10 ⁻⁴ to 30, and more preferably 10 ^{−3 to} 20% by mass. The drug according to any one of (86) to (91).
(96) The adhesive layer is present in 90 to 100, preferably 95 to 100% of the (A2 surface), and the surface of the layer is an adhesive surface (86) or ( 95) The drug described.
(97) The ratio of the pad parts in the order of (support | adhesive layer | pad part) is 1 to 100, preferably 10 to 100, more preferably 50 to 100% of all pad parts. (93) The drug according to (93).
(98) The outer surface of the cover or the outer surface of the abrading agent is hydrophobic, preferably the support itself is also hydrophobic, and the contact angle with respect to water droplets is 30 to 180, preferably 40. The agent according to (53) or (81), characterized in that it is ˜160, more preferably 50 to 130 degrees.
(99) 10 ^{−10 to} 0.9, preferably 10 ⁻ when the abrading agent or the cover has no diffusion rate of A1 or A0 to the skin surface between the A2 containing layer and the skin surface. ^The drug according to any one of (53), (81), and (93), which has a drug release control layer that is suppressed to ^{8 to} 0.2, more preferably 10 ^{−6 to} 0.05 times.
(100) The area of the surface that can be bonded to the peripheral portion is 1 to 90, preferably 2 to 50, more preferably 5 to 30% of the total area of the A6 or (A2 surface). The drug according to (90) or (91).
(101) The coating layer of A2 exists in the order of (support | adhesive layer | A2 coating layer), and the area ratio of the A2 coating layer is 1 to 100, preferably 10 to 99, of the total area of (A2 surface). More preferably, it is 30-95%, The chemical | medical agent as described in (86) or (88) characterized by the above-mentioned.
(102) A drug characterized in that the drug A2 of any one of (1) to (101) is a coated product obtained by applying the drug A2 on a support.
(103) The drug A2 contains one or more terpene compounds, preferably terpene compounds having 20 or less carbon atoms, in a total amount, preferably 0.0001 to 20, more preferably 0.01 to 10, More preferably, it contains 0.3-10 mass%, The chemical | medical agent as described in (1) characterized by the above-mentioned.
(104) The drug according to (1), wherein the terpene compound is preferably a monocyclic monoterpene or a bicyclic monoterpene, more preferably menthol, camphor, or borneol.
(105) The drug A2 is a monocyclic monoterpene and a bicyclic monoterpene in a total amount of 0.0001 to 20, more preferably 0.01 to 10, and still more preferably 0.3 to 5. The drug according to (1), which is contained by mass%.
(106) The A2 is a patch having the support according to any one of (58) to (101), and the outer surface of the nose has an intranasal entrance region (40 from the nasal entrance and the nasal entrance). , Preferably 0.1 to 100, preferably 1 to 99, more preferably 10 to 97, still more preferably 30 to 90% of the total area of the inner surface up to 30 mm (1) ) Drug described.
(107) The support has the spring elasticity, and by attaching the patch, the cross-sectional area of the nasal cavity is 1.05 to 10, preferably 1.1 to 5, more preferably 1.2 to 2. The agent according to (106), characterized in that it is used in a mode that doubles.
(108) The adhesive is applied to 5-100, preferably 20-100, more preferably 50-100% of the outer surface (the non-adhering surface). And the drug according to (106).
(109) The A1 or A0 is at least one of 1) an antihistamine, 2) a compound that suppresses the release of histamine, and 3) a compound having both effects, preferably 1) one of 2) It is the above, The chemical | medical agent of (1) description characterized by the above-mentioned.
(110) The antihistamine is preferably a compound of an alkylamine (preferably chlorpheniramine), an ethanolamine (preferably diphenhydramine), an ethylenediamine, a piperazine, a phenothiazine, or a pemilast. The drug according to (1), which is a compound of chlorphenamine maleates and diphenhydramine hydrochloride.
(111) The medicine according to (1), wherein the inside of the eyelid indicates a region where the hatched portion in FIG. 1 and the hatched portion in FIG. 2 overlap.
(112) (1) description, wherein the inside of the eyelid refers to the region of 5-1 in FIG. 6 (the half region on the eyeball side of the eyelid) and the region where the hatched portion in FIG. 2 overlaps Drugs.
(113) The drug according to (1), wherein the outer surface of the eyelid points to a region 5-2 in FIG.
(114) The allergic reaction is a reaction that occurs when histamine is released by an antigen-antibody reaction, preferably a reaction that occurs when the released histamine is received by an H ₁ receptor. The drug according to (1).
(115) After contacting the A2, an ointment base and / or a polymer having a molecular weight of 500 or more, preferably 1,000 to 1,000,000, more preferably 5,000 to 500,000 is added to the upper surface of the contacted A2. -99, Preferably it is 1-90, More preferably, the liquid substance containing 3-70 mass% is apply | coated, The chemical | medical agent of (1) description characterized by the above-mentioned.
(116) The viscosity (10 ⁻³ Pa · s) of the ointment base and the liquid is 1 or more, preferably 3 to 10 ⁴ , more preferably 10 to 3000, and the liquid contains a solvent. The agent according to (115), wherein the solvent is evaporated after the application, and the applied product is an application-type accompanying plaster that becomes a solid film.
(117) The polymer is an organic polymer and / or an inorganic polymer, and preferably comprises at least one of a synthetic polymer, a natural polymer, and a modified polymer (a product obtained by artificially processing a natural polymer). Is a natural polymer or a modified polymer, The agent according to (115).

Itching of the eyes due to hay fever was eliminated by bringing the drug A2 containing A1 into contact with the eyelids and absorbing it through the skin. The runny nose, sneezing and nasal congestion caused by hay fever disappeared when the drug A2 containing A1 was brought into contact with the outer surface of the nose and percutaneously absorbed. According to the present invention, the drug is delivered to the required location at the required time and in the required amount. Therefore, there is no general dullness and drowsiness as when taking medicines or injections. Also, once applied, it works for a long time. If it is no longer needed, it can be removed. I don't take medicine, so I won't make my stomach and stomach worse. When an injection is made, the entire amount of the drug is injected into the body in an instant, which gives a shock to the body, but since this drug enters the body with the wrinkle, there is no shock. Unlike eye drops, the drug supply is limited to the eyelids and does not go to the cornea or eyeball, so there is no damage to them. When the nostrils are completely closed due to nasal congestion, it is difficult to apply nasal drops because the drugs do not enter. It works with the drug of the present invention.
(1) Effect on eyes. Since the eyelid is thin, the allergic reaction inside the eyelid can be suppressed by bringing A2 into contact with the outer surface of the eyelid and allowing A1 or A0 to enter the skin. Many blood vessels (including capillaries) run in the eyelid, and this may have an effect of promoting the movement of A2 to the inside. By using this effect, the same effect as instilling eye drops into the eye can be obtained.
(2) The method of applying the coated material according to any one of (53) to (67) suppresses drying of the solution components in the drug and enhances the penetration. Moreover, since peeling off is prevented and a long-term effect is maintained, it is particularly preferable.
(3) When the applied material is pasted in the nasal cavity, even if a runny nose appears, A2 does not flow out because it is protected by the support. For this reason, it continues to exert its effect for a long time. A1 or A0 that has entered from the skin or mucous membrane moves to the peripheral part by blood vessels (including capillaries) and can suppress the allergic reaction. In the pasted place, adhesion of pollen to the mucous membrane is prevented and the reaction is suppressed. In an embodiment in which a pressure-sensitive adhesive is applied to the outer surface of the coated material, pollen adheres to the pressure-sensitive adhesive surface, and entry of pollen into the nasal cavity is suppressed, which is preferable.

Next, the present invention will be described in detail.
(II) Detailed explanation.
(II-1) A mammal.
The mammal is preferably a monkey, dog, cat, or human, more preferably a human.
(II-2) Eyelids and nose of eyes.
Eyelids are also called Ken Ken. Skin folds that open and close over the surface of the sleeper. The inside of the eyelid represents the hatched portion in FIGS. 1 and 2, which includes the conjunctival portion of the eye.
The nasal cavity refers to a cavity through which air entered from the nostril entrance passes before reaching the upper pharynx (or nasopharynx). The sinuses are also included. The inner surface of the nasal cavity refers to the surface in contact with the cavity. The outer surface of the nose refers to a portion surrounded by line 2-1 in FIG. 3, and is defined by (3).
2-2 in FIG. 4 indicates the center area of the face described in (36). The area inside the line connecting the edge of the lips and the center of the eye and below the eyebrows. It refers to the palatal surface existing in this fluoroscopic region.
The palatal surface in the oral cavity refers to the region from the tip of the gum (or gingiva) to the throat, preferably up to 50% of the region.
The surface on the oral cavity side in (34) refers to a region schematically indicated by a dotted line 3-2 in FIG. 5 and refers to a lower half region of the nostril.

(II-3) Allergic reaction.
Allergic reaction refers to an immune reaction that presents symptoms that are harmful to the body. The mechanism is considered as follows. When the antigen enters the body and is recognized, an antibody against the antigen is produced in vivo. By reacting the antigen and the antibody (referred to as immunoglobulin Ig), allergic substances are released from the cells, and allergic reaction (one or more reactions of hyperemia, itching, urticaria, tissue swelling, inflammation) Produce. In particular, the E type, IgE, is the main cause of the hypersensitivity reaction.
A compound that suppresses the reaction is called an antiallergic agent. There are the following mechanisms. 1) a compound that inhibits the process by which an antigen is recognized by the living body, 2) a compound that suppresses the production process of the antibody, 3) a compound that inhibits the reaction between the antigen and the antibody, and 4) suppresses the release of the onset substance. Compound, 5) a compound that invalidates the pathogenic substance, and 6) a compound that quenches the reaction. 1) to 5) remove the cause of the reaction, and 6) refers to a compound that quenches the reaction that has occurred. An antiallergic agent refers to a compound that inhibits one to all of this mechanism.

(II-4) Antigen.
In general, the antigen includes the following. 1) Plant pollen. Specific examples are pollen of large plants such as cedar, pine, cypress and birch, and herbaceous plants such as ragweed, nettle and rice. 2) House dust, 3) Food. Specific examples include mackerel, eggs, and buckwheat. 3) Pharmaceutical products. A specific example is penicillin. It is a compound that easily binds or adsorbs to body proteins and cells. Preferred are cedar, pine, cypress, ragweed and rice, more preferred are cedar, cypress and pine, and still more preferred are cedar and cypress pollen.
(II-5) Allergic substance.
As such substances, active amine compounds (specific examples are histamine, serotonin), protease, heparin, leukotrienes, prostaglandins, thromboxanes, Th2 type cytokines (IL-4, 5, 6, 13), platelet activation There are factors.

(II-6) Description of antiallergic agents.
1) A compound effective in the process of 5) of (II-3). Histamine released from mast cells and basophils is accepted by the H ₁ receptor and causes allergies. This is called the H ₁ action. A compound that blocks the reception of histamine and suppresses the onset by binding of the A1 to the receptor is referred to as a histamine H ₁ -antagonist (H ₁ -Blocker) or an antihistamine. As specific examples, a1) ethanolamines (amino ether type) (eg, diphenhydramine, carbinoxamine), a2) alkylamines (preferably propylamine type) “Example, chlorpheniramine, triprolidine, dimethindene maleate“ MJM ” A3) ethylenediamines (eg, hydroxyzine, meclizine, emedastine, tripelenamine), a4) piperazines (eg, meclizine), a5) phenothiazines (eg, promethazine, mequitazine), a6) others (mephydrin). Preferably, a1) and a2), more preferably chlorpheniramine maleate (MCF) and its d form, diphenhydramine hydrochloride (EJH).
The antihistamine is preferably a non-protein.
2) There are compounds that suppress the onset by suppressing the process of releasing histamine from mast cells and basophils. Specific examples include Na cromoglycate, tranilast, amlexanox, repirinast, tazanolast, traxanox, pemirolast.
3) A drug having the effects of both 1) and 2). Specific examples include ketotifen, azelastine, oxatomide, and terfenadine.
4) Leukotriene receptor antagonist. By binding to the receptor, it inhibits leukotriene reception and suppresses onset. Specific examples include 5-lipoxygenase inhibitors and leukotriene antagonists. There are pranlukast and ibudilast.
5) Platelet activating factor antagonist. A specific example is ibudilast. Ibudilast has antagonism against leukotrienes and platelet activating factors.
6) thromboxane A2 inhibitor,
7) Cytokine inhibitors.
8) Steroid agent. A compound having a steroid skeleton [chemical structure 1] is referred to as a steroid. Particularly, a corticosteroid released from the adrenal cortex is preferable, among which a glucocorticoid is preferable, and a compound having a hydrocortisone skeleton is more preferable. Among these compounds, in particular, a ketone group at the C ₃ position, a ketone group at the C ₂₀ position, a double bond between the C ₄ and C ₅ , a β-OH at the C ₁₁ position, and a ₂ between C ₁ and C 2 double bond, one-all of it has a fluorine group, the C ₉ position, preferably a compound having two-all is more preferable. Compound Example prednisolone such that the double bond has been introduced [acetic acid - succinic acid - methyl - prednisolone etc.], Petametazon compound having a skeleton obtained by introducing a fluorine group into the C ₉ position [phosphate -, butyrate propionate -Petamethasone etc.], dexamethasone [acetic acid-, phosphoric acid-, propionic acid-dexamethasone etc.], and triamcinolone [fluo-, hull-, am-sinonide etc.] are preferred.
Non-steroidal type is preferable, 1) to 3) are more preferable, and 1) is more preferable.

(II-7) A) The efficacy of steroids.
Has the following effects. 1) anti-inflammatory action, 2) immune response inhibitory action, 3) contract blood vessels. 4) Suppress most allergic symptoms. The action mechanism is as follows: 1) inhibition of arachidonic acid metabolism and inhibition of production of leukotrienes and prostaglandins, and 2) inhibition of migration and activation of inflammatory cells. 3) Suppresses the production of cytokines. 4) Promotion of β2 action, etc. It can be said that even when a biological tissue is subjected to immunological stimulation, it does not show a strong response to it. However, the whole picture is still unclear. When used in large amounts over a long period of time, there are dangerous side effects.
B) All precursor A0. A precursor refers to a compound that undergoes a chemical change to yield A1 after it has been absorbed transdermally. For example, it refers to a compound that produces A1 after a glycoside is hydrolyzed by an enzyme. When present on the skin surface, it does not act on the surface cells. Therefore, there is an advantage that even if the surface cells are in contact with the dense concentration, they are not damaged.

(II-8) Promotion of absorption.
In order to increase the absorption rate of the compound from the skin by 1.01 to 10 ⁵ , preferably 1.1 to 10 ⁴ , more preferably 2 to 10 ³ times, it is preferable to take the following method.
It is preferable that the coating composition contains an absorption accelerator in an amount of 0.001 to 95, preferably 0.01 to 90, more preferably 0.1 to 50% by mass. In the outermost layer of the skin, there is a barrier layer (a stratum corneum) in order to prevent foreign substances from entering. Mainly the layer prevents the percutaneous penetration of the drug. However, in order for the drug to enter the target location, it is preferable that the penetration rate of the drug is accelerated in all phases (denoted as B1) including the stratum corneum to the required location. As a method for the promotion, there is the following method in terms of mechanism.
According to Fick's diffusion formula, (diffusion substance amount / second) is the diffusion coefficient D1 and the concentration difference C1 / cm, increasing the affinity of the drug to B1, increasing the partition coefficient, and increasing the diffusion rate in B1. Since it is proportional to the area S1, it is sufficient to take measures to increase these. On the other hand, since the amount is inversely proportional to the thickness B2 of the diffusion layer, it is only necessary to make B2 as thin as possible.
There are two drug skin permeation pathways: 1) a pathway that penetrates the stratum corneum, and 2) a pathway that passes through pores, capillaries, sebaceous glands, and sweat glands (denoted as B3). It is preferred that permeation through at least one, and preferably both, is promoted.
In general, the stratum corneum has a natural moisturizing substance. Therefore, when water is replenished, the stratum corneum swells and absorbs water, loosens the structure of cell filling, and facilitates drug permeation. In general, since the stratum corneum is rich in lipids, it is difficult for a drug having a high ionic polarity to penetrate. A fat-soluble compound having a large (oil / water) distribution coefficient is likely to permeate. However, if it is too high, it is trapped in the stratum corneum or fat layer, and further diffusion into the inside is suppressed. Therefore, a compound having moderate fat solubility is preferred. The chelating agent is thought to expand the cell gap and promote the permeation by binding to Ca ²⁺ ions at the junction between cells. Unsaturated fatty acids such as oleic acid act on the lipid bilayer and promote it by increasing its fluidity.

Specific examples are as follows.
1) A group having affinity for B1 is bound to the compound. For example, a group having an optimally designed (hydrophilic / hydrophobic) ratio is introduced. That is, a method for modifying the molecular structure of a drug.
2) A method in which the higher-order structure of the stratum corneum is loosened to facilitate the passage of the drug. For example, water is applied to B1, and the layer is swollen and softened. A method for increasing the moisture content to the original 1.01 to 100, preferably 1.1 to 50, more preferably 1.3 to 20 times. a) A method in which moisture is applied to the skin in advance, the content is increased, and then contacted with the drug. b) A method for realizing the embodiment by incorporating a compound for increasing the content into the drug. The compound is called a humectant.
Specific examples of the humectant include glycerin, sorbitol, propylene glycol, hyaluronic acid, pyrrolidones, urea derivatives, and gum arabic. c) The moisture content of the skin can be further increased by applying a moisturizing cover after the chemical is applied. As the cover, a film-like cover having a low moisture permeability is preferable, and a support and an adhesive tape described later can be used. The tape is more preferably a tape containing one or more of a humectant, A1, A0, A2, A3, and a pad, and there are embodiments (53) to (67). d) A method of applying a patch described later. Two or more of these can be combined.
3) A method of softening and loosening the structure of the fat layer of the stratum corneum with an organic solvent other than moisture. Specific examples include DMF, DMSO, DMAC, fatty acids, and (lower to higher) alcohols.
4) a) A method in which a compound is present that increases the dissolution concentration of the drug in B1 (ie increases the partition coefficient). Examples of compounds are (lower to higher) alcohols, polyhydric alcohols, preferably ethanol, propanol and glycerin. b) The presence of compounds that increase the partition coefficient and / or increase the diffusion coefficient due to various combined effects. Examples of compounds include: Azone (1-dodecylazocycloheptane-2-one), a compound having a structure in which a fatty acid having an appropriate length is linked to a highly polar part, decylmethyl sulfoxide, a surfactant, (lower to higher grade) ) Fatty acids and their esters, medium chain glycerides, lecithins, monoterpenes, fatty acids, bile acids, chelating agents, salicylic acids.

5) A compound that increases the dissolution concentration of the drug in the coating agent by 1.01 to ∞, preferably 1.1 to ∞, more preferably 2 to ∞, and C1 is increased. That is, a solvent that dissolves A1 or A0 is present. You may make it exist in a chemical | medical agent previously, and may exist just before putting on skin.
6) Iontophoresis. A method in which a charged drug is forcibly fed into the skin by continuously applying an electric current to the skin from the outside, preferably in a pulsed manner. 7) Encapsulation of the drug. A method in which a drug is wrapped in an oblate such as an inclusion compound, a liposome, or an emulsion droplet, and easily passed through the stratum corneum. The oblate is preferably a compound that is decomposed in the body. Other capsules include spherical carbon molecules such as fullerene, and molecules with 1 to 10 substituents. The carbon number is 30 to 200.
8) Coolant. When the refreshing agent is present at the concentration, the skin and B1 and B3 are moderately stimulated and activated, and the penetration of the antiallergic agent into the skin is promoted.
9) It is more preferable that the accelerator does not enter the skin. Therefore, the size of the molecule can be increased. 5-1000 are preferable, as for the number of atoms which comprise a molecule | numerator, 10-1000 are more preferable, and 17-1000 are still more preferable. Regarding the details, reference can be made to the description in Reference 13.
10) Preferred method. It is most preferable to obtain the desired effect without leaving any scar on the skin tissue. For that purpose, it is preferable that the penetration amount of the drug through a) B3 is the mode of (18). This is because the drug can be delivered directly to the dermis and subcutaneous tissue without passing through the stratum corneum. At this time, it is preferable that the hair of the corresponding part is removed in the form of (17) because the penetration is further promoted. However, it can also be used without depilation. b) Softening of the stratum corneum with moisture is preferable because it is repaired without leaving any scratches.
11) If red, dirt, fat or the like adheres on the skin surface, the penetration rate is suppressed by them. In this case, it is preferable to previously remove the deposit in the form of (19) using one or more of paper, cloth, cotton, detergent, water, alcohol, etc. as the planned contact location. This has the effect of thinning B2. However, an aspect in which the removal rate is 0 to 4.99 can also be used.
12) It is preferable to increase the diffusion coefficient by intensifying the temperature effect and the molecular motion of the drug molecule, and to cause convective stirring with the skin surface and oils and fats in the surface. For this purpose, it is preferable to raise the temperature of at least one of the skin and the drug, preferably both in the manner described in the above (22) and (23). In the above description, an aspect in which the magnification is 1.0 to 1.01 times can also be used.

(II-9) Anti-inflammatory analgesic, vasoconstrictor.
An anti-inflammatory analgesic can be added to A2. Specific examples of the compound include the refreshing agent, and other salicylic acid esters and salts thereof (for example, methyl salicylate and sodium salicylate), borneols, glycyrrhizic acid, mecuenamic acid, indomethacin, and an anti-inflammatory enzyme (trypsin and the like).
Anti-inflammatory agents suppress inflammation, blood vessels contract, blood vessel wall permeability decreases, blood component leaching is suppressed, and swelling of living tissue is suppressed. Examples of the vasoconstrictor include phenylephrine salts, ethifermine hydrochloride, epinephrine, octopamine hydrochloride, naphazolines, and ephedrines.
(II-10) Coolant and fragrance.
In addition, it is preferable to contain a terpene refreshing agent or a fragrance that gives the medicine a refreshing feeling.
The terpenes are classified into hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, tetraterpenes, and polyterpenes according to the number of carbon atoms.
Preferred are terpenes having 20 or less carbon atoms, more preferred are monoterpenes, and more preferred are menthol, which is a monocyclic monoterpene, and camphor, borneol, which are bicyclic monoterpenes. When the drug contains a terpene compound in the embodiment described in any one of (103) to (105), the penetration rate is increased and the effect is increased, which is preferable. A1 or A0 and the terpene compound will have a special interaction.
(II-11) A warming agent.
A warming agent can be added to the drug. This is used in such a manner that the surface temperature of the skin is raised by 0.1 to 10, preferably 0.3 to 6 ° C. Specific examples of compounds are mustard oils and saicins, which are pungent components of pepper and mustard. It exists naturally in mustard glycosides, and when this is hydrolyzed, allyl isothiocyanate, a pungent component, is produced. Mustard oil is a general term for isothiocyanates.

(II-12) Dispersion medium A3.
A2 is preferably used in a form in which A1 or A0 is dissolved and / or suspended in a dispersion medium A3. A3 has a role of a dispersion medium for dispersing A1 or A0 and a role of adjusting the concentration of A1 or A0 to a suitable concentration. Since the permeation rate of A1 or A0 through the skin varies depending on the type of A3, A3 is also a regulator of the rate. A1 or A0 is preferably in the state of being dissolved in a molecular form because the speed of penetration into the skin is faster. Even in the suspended state, it is preferable to dissolve and penetrate. A3 promotes the dissolution.
The drug A2 may be in the form of 1) a solid, a plaster, or a powder, but 2) a semi-solid (such as an ointment, gel, cream, liniment, patch, patch), , Lotion, etc.). This is because 2) and 3) have better adhesion between the skin and A2, and better penetration of the drug into the skin. In any of 1) to 3), it is more preferable to use A3. In A), A3 may be in a solid or powder state, but in 2) and 3), A3 is semi-solid and liquid. A3 is classified into oily, aqueous, emulsion, and gel dispersion media. The details are as follows.
a) Oily dispersion medium. This refers to a lipophilic compound having a solubility in 1 L of water at 25 ° C. of 0 to 1 g, preferably 0 to 0.3 g, and a dissolution amount in 1 L of diethyl ether of 1 to ∞, preferably 10 to ∞ g.
“The oil-based dispersion medium liquid is a liquid having a flat contact surface at 25 ° C. and 1 atm., And a contact angle when a water droplet is placed on the liquid surface is 40 to 180, preferably 50 to 150. More preferably, the dispersion medium is 60 to 130 degrees, and the aqueous dispersion medium liquid is a liquid having a contact angle of 0 to 39.9, preferably 0 to 20 degrees, more preferably 0 to 10 degrees. Can also be defined. For the flat surfaces, materials that can be flatly developed can be selected. The molecular weight is preferably 20 to 10 ⁷ , more preferably ⁶⁰ to 10 ⁶ , and more preferably 100 to 10 ⁵ . A compound having 2 to 300 carbon atoms, preferably 4 to 200 carbon atoms, more preferably 8 to 100 carbon atoms is preferable.
Specific examples thereof include saturated hydrocarbons (straight chain, those having side chains, cyclic, polycyclic compounds), hydrocarbons having an unsaturated group, and aromatic hydrocarbons. There are compounds in which 1 to 10 ³ functional groups or different atoms are bonded, or compounds in which 0 to 50, preferably 0 to 10%, of the total number of carbon atoms are bonded. Examples of functional groups include alcohol groups, carboxyl groups, aldehyde groups, ether groups, ketone groups, amino groups, amide groups, halogen groups, thiol groups, thioether groups, and heterocyclic groups. Heterogeneous atoms include atoms (excluding C) with atomic numbers 3 to 92 in the periodic table. Regarding these details, the description in Reference 23 can be referred to.
Examples of the compound are as follows. Synthetic systems include ester oils and polyether oils. Minerals include solid paraffin, petrolatum, liquid paraffin, and silicone oil. In animal and plant systems, there are fats and oils (main components are glycerin esters, saturated and unsaturated fatty acids, long chain alcohols, hydrocarbons, and ketones). Since unsaturated fatty acids are prone to degradation, hydrogen can be added to saturate unsaturated groups. This increases the viscosity. There are single or a mixture of all two of these. Specific examples include various oils such as olive oil, oleic acid, lanolin, petrolatum, paraffin, wax, cetyl alcohol, stearic acid, and plastic base. Natural oils widely present in the animal and plant kingdoms are fatty acid esters, and a triester form with glycerin is the main component. The number of carbon atoms of the fatty acid is 2 to 30, preferably 4 to 25, and the number of unsaturated groups per molecule is preferably 0 to 10, and more preferably 0 to 5. In addition, there are the diesters and monoesters as accessory components. These are called simple lipids. In addition, there are also complex lipids containing one or more of phosphoric acid, sulfuric acid, sugar and amino groups, and derived lipids that are hydrolysates of lipids.
In general, the alcohol group is a lower to higher monohydric to polyhydric alcohol. There are 1 to 500, preferably 1 to 100, preferably 1 to 20 valent alcohols having 1 to 500 carbon atoms. Those that are not natural can be obtained by artificial synthesis. An example of a natural product is wax. These are esters of higher monohydric fatty acids and higher monohydric alcohols, which are liquid to solid at 25 ° C.
In addition, there are salts of the fatty acid and a basic compound. For example, there are salts with hydroxides such as NaOH, Ca (O) ₂ , NH ₄ OH, amines, and metal soaps.
Saturated alkanes. As the chain type, there are a linear type and a side chain type having a branching group. The cyclo form in which a ring is formed includes a monocyclic form having one ring and two or more polycyclic forms. Mixtures of these 2 to 300 species can also be used.

b) Aqueous dispersion medium. This refers to a hydrophilic compound having a solubility in 1 L of water at 25 ° C. of 2 to ∞, preferably 10 to ∞ g, and at least water. Specific examples include the following water-soluble polymers. In animal and plant systems, there are quinseed gum, xanthan gum, gum arabic, sodium alginate, pectin, starch, gelatin, casein, hyaluronic acid, and sugars (number of monosaccharides to ∞ sugars). Cellulose derivatives include methyl-, carboxymethyl-, and hydroxyethyl-cellulose. In the synthetic system, there are polyvinyl alcohol, pyrrolidone, and sodium polyacrylate. Inorganic systems include bee gum and bentonite. In addition, there is the humectant. These can also be used as humectants, aqueous thickeners, aqueous gelling agents, and aqueous suspending agents. These alone or a mixture of 2 to all kinds are used by mixing with at least water.
c) Emulsion dispersion medium. This is an emulsified liquid, and there are an oil-in-water type (written as O / W) and a water-in-oil type (written as W / O). There are ointments, creams and emulsions, and lotions. When an oil phase is added to an aqueous phase in which an emulsifier is dissolved while stirring, an O / W type is generated. When an aqueous phase is added to an oil phase in which an emulsifier is dissolved, a W / O type is generated. Water, alcohols, and aqueous A3 are used for the aqueous phase, and the oily A3 is used for the oil phase. The thickener is added to adjust the viscosity of the emulsion. As the emulsifier, a surfactant (anion-, cation-, amphoteric-, nonionic surfactant) is used, and a nonionic type and an anionic type are more preferable. A1 can be contained in any proportion in one or both of the continuous media in the emulsion droplets.
d) Gel dispersion medium. In a gel state, d1) an aqueous gel (gelled by containing at least water and a gelling agent) and d2) an oily gel (gelled by adding an oily gelling agent to liquid oil) is there. d1) absorbs moisture well and can be easily washed with water. Since it is easy to dry, the moisturizing agent is often added. Specific examples of the aqueous gelling agent include organic gelatin, gum arabic, alginate, carboxyvinyl polymer, methylcellulose, polyacrylic acid Na, polyvinyl alcohol, polyvinyl pyrrolidone, inorganic bentonite, and bee gum. The transdermal absorbability of the drug is good and preferable.
A specific example of the oily gelling agent is propylene glycol. In the case of an emulsion, A1 or A0 may be present in a continuous medium, may be present in fine droplets, or may be present in both. More preferably in fine droplets.
The thickener refers to a compound that, when added, increases the viscosity of the solution by a factor of 1.01 to ∞, preferably 1.2 to ∞, more preferably 2 to ∞. Call. There is a case where the compound itself thickens and a case where the compound thickens as an action of an intermolecular crosslinking agent between other compounds. Crosslinks such as electrostatic interaction, hydrogen bond, coordination bond, chemical bond.
Although 1-12 can be used for pH of a dispersion medium solution, 2-10 are preferable, 3-9 are more preferable, and 4-7 are still more preferable.

(II-13) Preservatives and bactericides (A4).
It is preferable to contain a preservative so that various germs do not propagate in the drug. The preservative has a bactericidal action and a growth-preventing effect against bacteria, but is preferably harmless or less harmful to the skin. However, since there are few innocuous ones, it is preferable to reduce the addition amount as much as possible and to select A3 which may be small.
Specific examples of preservatives. Benzoic acids [for example, p-hydroxybenzoic acid esters (parabens, etc.), salicylic acid and its esters and salts (salicylic acid, phenyl salicylate, etc.)], phenoxyethanol, phenols [thymol, 2-phenylphenols, isopropylmethylphenol Etc.), pyrithiones (such as pyrithione Na and zinc pyrithione), downsil 200, alcohols (such as ethanol and propanol), esters, acids (such as organic acids), aldehydes, terpenes, and perfume oils.
(II-14) Other additives.
In order to improve the liquid properties such as coating properties of A2, surfactants (positive, negative, amphoteric, non-ionic surfactants), and to adjust the viscosity of A2, the thickener, A2 and Moisturizing agent to keep skin's humidity moderate, cosmetic agent (whitening agent, coloring pigment, white pigment, whitening agent, coloring agent) to make A2 cosmetic, UV absorption to protect skin from ultraviolet rays Antiperspirants that suppress the release of sweat from the skin, nutrients for the skin (vitamins, amino acids), hormones, deodorants (deodorants), sebum inhibitors that suppress the release of sebum, and drugs One to all kinds of antioxidants and fragrances that prevent oxidation can be contained in A2 at suitable concentrations. The viscosity of the drug can be adjusted by adding the thickener.
The mode in which the drug is applied to the skin surface is similar to the mode in which the cosmetic is applied. Therefore, a material used in cosmetics and a combination of materials can be used. Dispersion medium used in cosmetics, the surfactant, moisturizing agent, thickening agent, film forming agent, ultraviolet absorber, antioxidant, stabilizer, preservative, sequestering agent, whitening agent, vasodilator, hormone One to all kinds of agents, astringents, colorants, fragrances, cosmetics and nutrients can be used in suitable amounts.
It is preferable that 20 to 100, preferably 50 to 100, more preferably 80 to 10% of the main component types of A3 are the same as the main component types of commercial cosmetics, and the mass% of each component type corresponds to the cosmetics. It is preferable that it is 0.1-10 of the mass% of a component seed, Preferably it is 0.3-3, More preferably, it is 0.6-2 times. Here, the main component species represents a compound species of 1 to 8, preferably 1 to 4 positions in order of content. Therefore, 1) the role of makeup, 2) the skin moisture content is increased 1.01 to 10 ³ , preferably 1.05 to 100, more preferably 1.2 to 30 times, 1) One or more of the role of supplementing nutrients (vitamins, fats, amino acids) to the skin tissue and increasing its content by 1.01 to 100, preferably 1.1 to 30 times The role of can be given.
The content of the compounds described in (II-9) to (II-11), (II-13) and (II-14) with respect to the total drug amount is 10 ⁻⁵ to 50, preferably 10 ⁻⁴ to 30. Preferably it is 10 < ^-3 > -15 mass%.

(II-15) Drug form.
The drug is mainly used in the semi-solid form or liquid form. This will be described in order. Description will be made in the order of the hardness of the medicine. 1) A plaster. A salve that does not melt at room temperature but develops stickiness when in contact with body temperature. 2) Ointment. A mixture of plastic or fluid dispersion medium (oil, fat, petroleum jelly, glycerin, gel substance, etc.) and A1. In order of increasing viscosity, they are called ointments, creams, emulsions, emulsions, and lotions. It is 0.601 to 1000, 0.101 to 0.6, 0.0101 to 0.1, and 0.001 to 0.01 in order in terms of viscosity (Pa · sec). 3) Liniment. This refers to an external preparation (corresponding to the cream, emulsion and emulsion) having an intermediate viscosity between ointment and lotion, and is classified into the following four types. a1) Ethanolic solution type. Oil is often added based on ethanol. Good skin permeability. a2) Oily solution type. Oils with various drugs dissolved. a3) Emulsion type. O / W type emulsion using soap as an emulsifier. a4) Suspension dosage form. An insoluble drug is refined and mixed with a viscous liquid of a suspending agent (representing the thickener such as gum arabic). 4) Lotion agent. Liquid external preparations produced by dissolving or finely dispersing a drug in the aqueous dispersion medium, and are classified into a) suspension, b) emulsion, and c) solution. Components a) and b) may be separated during storage, but may be used by shaking before use. 5) Aerosol. This refers to an embodiment in which a solution, suspension, or the like is ejected in the form of a mist by the pressure of a liquefied gas or a compressed gas filled in the same container or another container.

(II-16) Drug release control layer.
A mode in which the control layer is provided between the drug part and the skin. It prevents the high concentration drug part from coming into direct contact with the skin. Further, since the drug is continuously diffused and supplied through the layer, the drug is supplied to the skin surface at a suitable concentration for a long period of time. The control layer refers to a layer that creates a difference in density of A1 or A0 in the form (31) between both surfaces.
In the embodiment having the pads of (93) and (94), it is preferable that the control layer is provided by adding a large amount of A2 to the pad in the embodiment of (99), because it is effective for a long period of time.

The basic configuration in this case is the order of (drug part / control layer / skin). Specific examples of the material of the control layer include the oil-based dispersion medium and the hydrophilic dispersion medium film (sol film or gel film thereof), the porous film of the support described later, woven fabric, non-woven fabric, and pad. It may be used in combination with a drug part before use, or after the layer is placed on the skin, the drug part may be placed thereon. A mode in which the applied part is applied to the skin and a control film is provided, and then the drug part is placed thereon; after the application liquid is applied on the drug part of the patch and the control film is provided, it is applied to the skin. There is a mode of attaching. The drug part may be applied and installed, or may be installed in a mode in which a patch is applied. There is a mode (36) as the porous membrane. The thickness is 10 ^{−6 to} 6, preferably 10 ^{−4 to 3} mm. However, there is also an aspect in which the thickness is 0 to 10 ⁻⁶ mm.
Specific examples include the control layer mode used in nitroglycerin patches, such as polyvinyl alcohol and silicon films.
However, an embodiment in which the difference in density is 0 to 1.099 can also be used. In the case where A1 is an oily substance, the control layer is more preferably in an aqueous form. In the case where A1 is an aqueous substance, the control layer is more preferably an oily aspect. That is, the control layer is a layer that controls the passage speed of A1 to 10 ^{−10 to} 0.9 when there is nothing, preferably 10 ^{−8 to} 0.2, more preferably 10 ^{−6 to} 0.05. Some are preferred (similar to A0). Since this can be realized in the pressure-sensitive adhesive layer, a pressure-sensitive adhesive layer having an optimum thickness can be used as the control film.

(II-17) Drug encapsulation.
A mode in which the drug comes out of the capsule when the drug is contained in a minute capsule and a trigger is applied may be used. Examples of the trigger include mechanical destruction such as rubbing by hand, and chemical destruction caused by supplying water or saliva. When an allergic symptom appears, the drug is released and effective just by rubbing the applied or pasted drug by hand or applying saliva.
Regarding the method for microencapsulating the drug, the description in Reference 24 below can be referred to. A specific example is a method in which the drug is first microparticulated and dispersed in a suitable dispersion medium, and then a film is formed on the surface and coated. Specific examples of the film forming method include the following three methods. 1) Chemical method (interfacial polymerization method, insolubilization reaction method), 2) Physicochemical method (phase separation method, interfacial precipitation method), 3) Physical method, mechanical method (spray drying method, air suspension coating method) )

(II-18) A patch.
The aspect which the part which has a chemical | medical agent also has adhesiveness like the salon pass of Hisamitsu Pharmaceutical Co., Inc. This embodiment is also called a plaster or a plaster. This is an embodiment in which a drug is contained in an adhesive and this is coated on a support. In order to improve the adhesiveness between the two, it is preferable to provide an undercoat layer between them.
The pressure-sensitive adhesive has at least 1) a rubber elastic body and 2) a tackifier that is compatible with the rubber elastic body and increases the adhesion to the skin. 3) Softener (having the effect of reducing the viscosity of the adhesive and improving the adhesiveness) 4) Filler (for the purpose of improving adhesiveness and cohesiveness and coloring) is added according to the purpose. To do. Furthermore, a colorant and an antioxidant are added depending on the purpose. The pressure-sensitive adhesive is selected from those having good solubility and dispersibility with respect to A1 or A0, and further having good diffusibility of A1 in the pressure-sensitive adhesive. Or a thing with good suspendability is selected. Furthermore, the thing with little harm to skin and excellent adhesiveness is selected. An adhesive refers to a substance that adheres to the skin when pressed against the skin.
Specific examples of the rubber elastic body include natural rubber and synthetic rubber (silicon rubber, acrylic rubber, styrene-butadiene rubber, isoprene, polyacrylic ester). Specific examples of 2) include rosin and its derivatives, terbene resins, aliphatic hydrocarbon resins, and aromatic petroleum resins. Specific examples of 3) include lanolin, polybutene, liquid polyisobutylene, animal and vegetable oils, and liquid paraffin. Specific examples of 4) include zinc oxide, titanium dioxide, calcium carbonate, silica, kaolin, and pentonite. In order to prevent the adhesive from remaining on the skin surface when the patch is peeled off, it is preferable to give the adhesive an appropriate cohesive strength. 4) increases the cohesive strength.
5) Back treatment agent. When the roll-shaped adhesive is rewound, a back treatment agent is applied to the back surface of the support so that the adhesive does not migrate to the back of the support. 6) Liner. In the case of a sheet like an emergency bond, a protective film for protecting the adhesive part is pasted on the adhesive part. Crepe-like film, cellophane, polyester, polyolefin film, release paper, etc. are stretched. Remove it before use. 7) Undercoat layer. It is used for the purpose of improving the strength and water resistance of the support to enhance the adhesion between the support and the adhesive. As a specific example, a substance (the rubber or synthetic resin) having affinity for both is applied. In addition, a method of increasing the adhesion by corona discharge treatment of the support, or a method using both of them is used. 8) There are an aspect in which the patch has a spring and an aspect in which it does not have a spring. Having a spring is preferable because it can be applied to the outer nose in the form of a nasal enlarged bansoko to enlarge the nostril. A mode in which the cross-sectional area of the nostril is enlarged to 1.05 to 10, preferably 1.1 to 5 times is preferable. A spring refers to a material having elasticity against bending deformation. It is preferable that the shear modulus is 0.01 to 300, preferably 0.05 to 200, more preferably 0.1 to 100 Pascal Pa.
There are metal springs, inorganic or organic polymer material springs, and organic polymer materials are more preferred. Regarding the details, the description of the mechanical property terms of the materials of References 4, 22, and 23 can be referred to, and regarding the patch, the descriptions of References 5 and 14 to 16 can be referred to.
The adhesive having the most preferable adhesive strength is preferably used for the adhesive strength. An embodiment in which drugs having various adhesive forces can be prepared and a user can select a preferable one is preferable.

(II-19) An embodiment of a poultice.
A mode in which the cataplasm contains A1 or A0. A poultice is made in a mud or coated on a cloth and is also called a poultice. The surface is covered with a liner. An essential oil component or drug mixed with a base material mainly composed of a water-soluble polymer. A specific example is a mixture of glycerin, water or other liquid substance (for example, propylene glycol), and further added a drug and an essential oil component. A patch containing A2 is applied to the surface of the skin and applied with an adhesive tape from above. Alternatively, after applying A2 to the skin, the poultice is applied, and an adhesive tape is applied from above.
The content of A1 or A0 in the adhesive layer of the patch and the content of A1 or A0 in the mud-like coating layer of the cataplasm is 0.0011 to 99, preferably 0.01 to 90, more preferably. Is 0.1-50 mass%.

(II-20) The contact method of the drug A2.
A) A method of applying A2 described in (II-5) on the outer surface.
The finger of a hand may be used, or it may be applied directly from a medicine container. An application part may be provided in a container and it may apply with it. For example, a method of pressing a container and extruding A2 through the porous membrane and applying it to the skin. When not in use, the porous membrane is sealed with a lid. Aerosol may be sprayed with eyes closed or with protectors on.
B) A method of applying a cover on A2 after coating.
The purpose of covering is 1) to prevent the evaporation of the components of A2 and moisture of the skin, and 2) to protect the applied A2. For example, A2 is prevented from adhering to a hand or another object when it comes into contact. 3) Prevents rubber and dust from adhering to the applied A2, and 4) Prevents the applied A2 from being oxidized and altered by air. 5) When the cover contains a moisturizing agent or a dispersion medium A3 having a high water content, the skin humidity is kept moderate, and the effect described in 2) of (II-8) is obtained. 6) When the cover contains A1, since A1 or A0 is continuously supplied from the cover, it becomes effective for a longer time. Since this embodiment is to paste the embodiment of C) described later, it can be referred to. 7) When the cover is waterproof as in (98), it prevents rain and water from splashing and being washed away.
The cover includes a bendable material and a non-flexible material. The former is preferred. A material that can cover and cover the uneven surface is preferable, and flexible bendable tapes and sheets are preferable. Forms include woven fabric, non-woven fabric, paper, sheet material, tapes, film, porous membrane, and foil, preferably a film-like sheet material.
The cover may or may not have an adhesive ability. In the former case, an adhesive tape is further applied and fixed from above.
The cover may or may not have a pad. The role of the pad is as follows. 1) Where the pad portion is present, the adhesive layer is prevented from coming into contact with the skin for adhesion, and the adhesive layer is prevented from adversely affecting the skin. 2) If the applied medicine melts with body temperature or sweat and falls down, the pad part absorbs it and prevents it. 3) When 1 to 4 kinds of moisturizing agents, A1, A0, A2 and A3 are contained, a pad portion is provided, and if this is contained, a larger amount of the substance can be retained, which is longer. It is preferable that the drug can be continuously released over time. Therefore, a pad having a suitable area and thickness can be provided according to the purpose.
Here, the pad is more generally defined by (64). Specific examples include woven fabrics, nonwoven fabrics, porous membranes, brushed fabrics, sea line-like materials, and cushion materials. The water in the pad can go outside. 1) What stuck this pad on the adhesive bond layer on a support body, 2) Furthermore, you may contain 1-4 types of moisturizer, A1, A0, A2, A3, and the pad containing them is included. You can paste it.
In the case of the patch of (II-18), A1 or A0 of the inner phase passes through the high-viscosity adhesive layer and reaches the skin surface, so the diffusion rate is slow. On the other hand, this embodiment is more preferable because it can be selected with a large diffusion rate of A1 or A0 to the skin surface because it does not exist. Further, since there is no obligation to dissolve A1, the adhesive can be selected in a wider range.
There are natural polymer, semi-natural polymer, synthetic polymer and metal for the material of the cover and the pad, and the description in (II-22) can be referred to.
Examples of the adhesive tape for the cover include the following. 1) A mode in which almost the entire adhesive surface can be bonded to the skin, 2) A type in which only the peripheral part of the tape can be bonded, and a type in which only the peripheral part on the short side of the rectangular tape can be bonded. 3) A mode in which there is nothing in the non-adhesive part, 4) A mode in which the above-mentioned 1 to 4 types of substances are present, 5) A mode in which the pad containing nothing is present, and 6) The pad contains the above 1 to 4 types There is a mode to do. A specific example of 1) is to create a bond, and a specific example of 5) is an emergency attendant. 7) A mode in which there is an adhesive layer on almost the entire surface of the support, and 1 to 4 types are present on an area of 1 to 99, preferably 10 to 98, more preferably 40 to 90% thereon. There is.
C) A patch containing A2 is pasted.
Since the two steps B) are performed in one step, labor can be saved. As the mode, there are the following modes.
1) A mode in which A2 is installed on a support. The description of (54)-(57), (74), (75), (II-22) can be referred to as the support. In order to improve the adhesiveness between the support and A2, an undercoat layer can be provided between them. This is stuck on the outer surface and further fixed with an adhesive tape. 2) A patch containing an adhesive layer and A2 is stuck on the support. As an aspect in which the adhesive layer is present on the support, there are the aspects (86) to (97). Aspect (96) is the aspect described in (II-18). Advantages of this embodiment are as follows: a1) Almost the entire surface can be adhered, and the adhesive fixing property to the skin is excellent. a2) Cut with scissors etc., you can choose the size and shape freely. a3) The drug is present in the entire applied area and works. a4) The manufacturing method is simple and the cost is low.
When the pad of (93) is provided, there is the advantage described in the above item B), and when the embodiment of (99) is used, there is an advantage described in (II-16). In addition, the aspect which contains A1 or A2 by (53)-(100) and the said B) term can be referred.

(II-21) Adhesive tape.
Most of the adhesive tapes are adhesive tapes in which an adhesive is applied on a support. The support described later can be used as the support. It is preferable to provide the undercoat layer between the two.
The pressure-sensitive adhesive contains at least 1) a rubber elastic body and 2) a tackifier. Depending on the purpose, 3) softener and 4) filler are added. Furthermore, a colorant, an antioxidant and a preservative are added depending on the purpose. Regarding these, the above description can be referred to.
Production methods of the tape include 1) a hot-pressure spreading method (applying heat to soften the adhesive) and 2) a solvent spreading method (softening by adding a solvent). .
The adhesive tape is preferably one having less damage to the skin, and more preferably a medical adhesive. Those that do not invalidate A1 and A2 are selected. As the tape, any known adhesive wound can be used. This is a mixture of rubber, resins, zinc oxide and other substances to form a sticky substance, which is applied onto a support such as cloth or paper. Zinc oxide has convergence, filler and antiseptic effects. Less irritating to the skin and strong stickiness.
Regarding the adhesive, the material of the adhesive tape, the production method, the adhesion mechanism, and the characteristics, the description in Document 26 can be referred to.

(II-22) Support.
Paper, woven fabric, nonwoven fabric, film, and metal foil are used, and a sheet shape having a thickness of 0.001 to 5, preferably 0.01 to 2 mm is preferable. It is preferable that it is flexible and flexible in order to be able to be applied to the uneven portion. Materials include natural polymer materials (eg, cellulose, protein, cotton, wool, hemp), synthetic polymer materials (eg, polyvinyls, polyethylene terephthalate, nylon, polyvinyl chloride, etc.), processed semi-natural polymer materials (Eg, cellulose acetate, human silk, etc.), metal materials (gold, silver, aluminum, alloy foil, etc.) alone, or two or more composite materials. Although hue, saturation, and lightness can be in any form, skin color is preferable because it does not stand out.
Those that do not allow the drug component to permeate are preferred. The support preferably has a moisture evaporation rate of 0 to 90, preferably 0 to 20, more preferably 0 to 2, and still more preferably 0 to 0.1% as compared to the case without the support.
Furthermore, there is an aspect in which the length can be extended to 1.05 to 10 times, preferably 1.2 to 5 times, and an aspect in which the length is not extended. Further, there are modes having the rubber elasticity and modes having no rubber elasticity. You can choose according to your purpose. A surface coat layer can be attached to the outer surface side of the support according to the purpose. For decoration purposes, support modification and protection, and reflectance adjustment. In order to adjust the glossiness, the outer surface is embossed, surface-coated, etc., and the reflection intensity according to Snell's law is 0.01 to 99, preferably 0.03 to 70, more preferably 0.1 to 20%. It is preferable to reduce it.
It is preferable that at least the outer surface of the support is waterproof. Even if it is raining or watering, there is little effect. The support itself is preferably waterproof. The contact angle of water droplets at 25 ° C. on the plane is 30 to 180, preferably 40 to 160, more preferably 50 to 130 degrees. However, the one of 0 to 29.9 degrees can be used according to the purpose.
The support is porous and can appropriately pass moisture. The number of holes is 1 to 10 ¹⁰ per cm ² , preferably 3 to 10 ⁶ .
The contrast in (74) refers to | IA-IB | / (2IC) where the optical intensity of the outer surface of the support and the skin is IA and IB, and the average intensity is IC. The image intensity refers to the lightness, saturation, and hue values of the Munsell color system. Regarding the color of the outer surface of the support, it is preferable that the requirement of (74) is satisfied in the 1-3 kinds of contrasts. Regarding the details, reference can be made to the description in Reference 25 below.
With respect to the support, any known support and material can be used as a support for general and medical pressure-sensitive adhesive tapes and as a photographic support. For details, refer to Chapters 11 and 12 of Reference 4 below. , 5-9, 14-16, 22, 23 can be referred to.

(II-23) Others.
As materials used for the manufacture of medicines, all sterilized materials are used. The alteration of pharmaceuticals is often caused by oxygen oxidation. Therefore, an embodiment in which the oxygen content in the product is reduced is preferable. It is preferable to reduce the oxygen content to 0 to 50, preferably 0 to 10, more preferably 0 to 1% of the oxygen content when prepared without taking special measures. It may be replaced with an inert gas (specific examples include nitrogen gas, carbon dioxide gas, He, Ar gas).
The saturated alkanes have low reactivity with other substances and have almost no adverse effect on the skin. Because it is tasteless, it is difficult for bacteria to propagate. Therefore, the amount of A4 added may be small. Since it has good adhesion to the skin, it can be preferably used as A3. Alkanes having 4 to 300 carbon atoms, preferably 6 to 200 carbon atoms, more preferably 10 to 100 carbon atoms are preferable. It is preferable to use the single or 2-100 types of mixture.
Human skin is covered with natural oils A5 released from sebaceous glands and sweat glands. Applying a drug of the same quality will have good affinity with the skin. Accordingly, 20 to 100, preferably 50 to 100, more preferably 80 to 100% of the main component species of A3 are preferably the same as the main component species of A5, and the mass% of each component species is A5. It is preferable that it is 0.1 to 10, preferably 0.3 to 3, more preferably 0.6 to 2 times the mass% of the corresponding component species. Here, the main component refers to a compound type of 1 to 8 positions, preferably 1 to 4 positions in order of content.
The aspect of (23) can be used preferably. That is, fat in the skin is released outside the body due to an increase in the surface temperature of the skin. Next, when A2 is applied and the temperature is lowered, A2 is sucked into the hole of B3. When this is performed 1 to 100, preferably 2 to 100, more preferably 4 to 100 times, the percutaneous absorption rate of the drug is further increased.
When the aspect of (8) is used in combination with the present invention, the effect is further enhanced, which is preferable.
The present invention can be used in combination with the conventional method for suppressing allergic reaction. However, the dose is preferably 0 to 90, preferably 0 to 50, more preferably 0 to 20% of the conventional dose.
For details and specific examples of the immune reaction and the antiallergic agent, the absorption promotion and promotion described in References 1 to 3 and References 10, Chapters 10 and 13, References 14 and 15, Reference 22 For the agent, the descriptions in Documents 6, 13, and 16 are described. For the preservative and the disinfectant, the descriptions in Documents 10 to 12 are described in surfactants, emulsified dispersions, (II-8) to (II-20) ( Regarding the details of other additives) and aspects, the description in Chapter 10 of Document 4, Documents 6, 9, 14 to 21, and Chapter 19 of Document 22 can be referred to, including cosmetic aspects.
Regarding the details of A3, in addition to the dispersion medium for external medicine, the description of the dispersion medium for cosmetics and the dispersion medium for AgX photographic emulsion can be referred to. Reference can be made to the descriptions in Chapters 10 to 14, References 5, 6, 9, and 16-22.
Regarding the details of the drug release control layer, plasters, ointments, creams, emulsions, emulsions, lotions, liniments and cataplasms, the descriptions in References 6 and 14 to 18 are given as adhesive tapes, adhesive tapes, undercoat layers, With regard to the patch, the description in Chapter 10 of Document 4 and Documents 5, 6, 16, and 23 can be referred to.
As the ointment base and polymer described in (115), dispersion media and compounds described in (II-12) to (II-15) can be used. In addition, there are proteins, gelatin, cellulose, and modified products thereof. Collodion and its addition of castor oil are used for medical purposes as a protective film for skin and wounds. This is a nitrocellulose called piroxylin. This can also be preferably used. The nitrogen content (%) is 5 to 20, preferably 10 to 15, and the coating amount is a monomolecular layer or more, 2 mm thickness or less, preferably 1 mm or less. The polymer is preferably soluble in water or alcohols, preferably water or ethanol. With respect to these, the descriptions in Documents 4, 5, 6, 9, 16 to 22 can be further referred to.

(Reference)
1. Medical terminology library, edited by Rachien et al., Allergies, Yodosha (1996).
2. Jiro Koyama et al., Fundamentals of Immunology, Tokyo Chemical Doujin (1989). Jiro Koyama, Immune Mechanism, Chemistry Doujin (1996). Edited by Yuichi Yamamura et al., Modern Immunology, Medical School (1992).
3. Translated by Teruyuki Yanagisawa, Katsung, Pharmacology, 8th edition, Maruzen (2002). Edited by Shuji Takafold, Pharmacology, Hirokawa Shoten (1996).
4). The Chemical Society of Japan, Chemical Handbook, Applied Chemistry, 5th edition, Maruzen (1995).
5. Encyclopedia of adhesion and adhesion, Asakura Shoten (1986).
6). Edited by Kamigama Kane et al., Latest pharmaceutical sciences, Hirokawa Shoten (2000).
7). Edited by Keizo Miyasaka, Plastic Encyclopedia, Asakura Shoten (1992).
8). Edited by Ihouchi et al., Polymer film and functional membrane, Gihodo (1991).
9.1) Research Disclosure, 1996, September issue, item 38957, Kenneth Mason, UK, 2) Encyclopedia of cellulose, November 2000, 1st edition, Asakura Shoten, 3) Polymer Dictionary, 1994 Maruzen, 4) Water-soluble polymer development technology, CMC (1999), 5) New polymer material One Point 4, superabsorbent polymer, Kyoritsu Shuppan (1987).
10. Bacteria prevention handbook, Gihodo (1986).
11. Translated by Koichi Yoshimura et al., Antiseptic / Fungicide Science, Fragrance Journal, Tokyo (1990).
12 Supervised by Tamio Nishimura, basic knowledge of antibacterial, Techno System (1998).
13. Hashida Mitsuru et al., In vivo drug delivery science, industrial books (1994), chemistry and education, 46, 7, 418-419 (1998).
14 Edited by Toshio Miyazaki, Encyclopedia of Medicine, Asakura Shoten (2001).
15. Pharmaceutical Science Dictionary, Hirokawa Shoten (1990).
16. Edited by Akinobu Otsuka et al., Pharmaceutical Sciences, revised 3rd edition, Nanedo (1997).
17. Edited by Takeo Mitsui, New Cosmetic Science, Nanzan-do (1993).
18. Latest Cosmetic Science, Yakuji Nipposha (1992), Takeo Tamura et al., Cosmetic Science, Flegrance Journal (2001).
19. Edited by Organic Synthetic Chemistry Association, Solvent Pocket Book, Ohmsha (1994). The same edition, Dictionary of organic compounds, Kodansha (1985).
20. Horiguchi Hiroshi, New Surfactant, Sankyo Publishing (1975).
21. Oil and fat chemical manual, Maruzen (1990), revised 3rd edition.
22. Chemical Handbook, Applied Chemistry, 6th edition, Maruzen (2003).
23. Chemical Handbook, Basics, 5th edition, Maruzen (2004).
24. Kondo, et al., Microcapsule, Sankyo Publishing (1987).
Kondo Asashi, Microcapsule, Nikkan Kogyo Shimbun (1970), supervised by Kondo Yasushi, Microcapsulation Technology, General Technology Center (1987).
25. Written by Nagatoshi Ariga, Encyclopedia of Photography, Chapter 5, Asakura Shoten (1983).
26-1) Translated by Hiroshi Mizumachi, Encyclopedia of Adhesion, Asakura Shoten (1993).
-2) Adhesion Science Committee, Adhesion, Theory and Application, Maruzen (1965).
-3) Toshinao Okitsu, actual knowledge of adhesives, Toyo Keizai Inc. (1980).
-4) Kitazaki, N., Adhesives learned from the beginning, Industrial Research Committee (2001).
-5) The latest application technology for adhesive products, DISC Corporation (1989).
-6) Market of '95 functional adhesives and adhesives, launched by DISC Corporation (1995).

[Example]
EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited to this.

Example 1A
To 100 g of purified water, 6 g of glycerin, 0.5 g of hyaluronic acid as a humectant, and 0.2 g of isopropylmethylphenol as an antiseptic / bactericidal agent were added and heated to 75 ° C. and mixed. 90g of stearyl alcohol as an oil dispersion medium is heated and dissolved at 70 ° C, then 0.1g of paraben as an antiseptic / bactericidal agent, 2g of diphenhydramine as an antiallergic agent, 4g of l-menthol as an aroma / coolant, 1.2g of dl-camphor Then, 0.7 g of glycyrrhetinic acid as an anti-inflammatory agent, 0.2 g of tocopherol acetate as an antioxidant, and 4 g of glyceryl monostearate as a surfactant were added and mixed. This oil was added to the aqueous phase, and (O / W) type emulsification dispersion was performed with a homogenizer. After deaeration, the temperature is lowered to 60 ° C., 0.2 g of glycine is added as a pH adjuster, 25 g of carboxyvinyl polymer (20% by mass aqueous solution) is added as a thickener and a film forming agent, and NaOH is used as a thickener. (1N water) was added to adjust the pH to 6.5. The temperature was lowered to 20 ° C. to obtain drug N1.
About 0.15 g was applied on 80-100% of the eyelid (shaded area in FIG. 2) of the eye which had become extremely itchy due to cedar pollinosis. After about 5 minutes, almost no itching disappeared, and there was no recurrence of itching for about 6 hours. No drowsiness occurred.
(Example 1B)
The same was applied until N1 was applied in Example 1A. After application, 1 minute later, with a cotton pad, a skin-colored adhesive band B4 (made of polyvinyl chloride and with an acrylic acid-based adhesive) was pasted on the coated surface. Covered 80-100% of all coated surfaces. One piece of cloth made up 75% of the bond, and was glued around it. In this case, the itch disappeared in about 5 minutes after the application, and thereafter no itch was produced for about half a day. The bond creation suppressed the water evaporation rate to 0.01% or less.
(Example 1C)
About 0.18 g of N1 was previously applied to B4, and this was pasted on the eyelid in the manner of Example 1B. After about 5 minutes, the itch disappeared, and then itching did not occur for 16 hours.
(Example 1D)
The same drug N2 was prepared except that the amount of diphenhydramine added in Example 1A was tripled. First, 0.15 g of glycerin was applied to the eyelid with a finger to provide the control layer. Next, 0.18 g of N2 was applied to the bond creation and pasted thereon. It took about 10 minutes until the itch disappeared, but after that, itching did not occur for about 1 day. This confirmed the effect of the control layer.
(Example 1E)
First, a bond was created on the eyelid, and then about 20% of the existing hair was removed by peeling it off. Next, 0.15 g of N1 was applied over 100% of the eyelid. After about 4 minutes, almost no itching disappeared, and there was no recurrence of itching for about 6 hours. There was no drowsiness. Similarly, in the embodiments of Examples 1B to 1D, there was an effect of the hair removal for shortening the time until the effect appeared.
(Example 1F)
First, the eyelid was heated by heating to about 47 ° C. on the eyelid and pressing a squeezed wet towel. The towel was removed and a bandage heated to 47 ° C. in the same manner as used in Example 1C was applied to the eyelid within 15 seconds. Itching disappeared after about 4 minutes, and no itching occurred for about 16 hours thereafter.
(Example 1G)
Except for the peripheral portion of the accompanying wound, 0.18 g of N2 was applied, and a 0.12 mm thick porous film was layered thereon as a control layer. This was put on the eyelid. Thereby, the same effect as Example 1D was acquired, without soiling a finger.
Example 1H
After applying the drug in Example 1A, the collodion solution was applied to the eyelid 70-95% of the eyelid 20 minutes later using a brush. This did not cause itching for about half a day.
The collodion solution is prepared by dissolving 10 g of pyroxylin in a mixed solution of 75 mL of ether and 25 mL of 95% alcohol, and adding 0.5 g of benzyl alcohol thereto.
(Comparative Example 1A)
About 0.2 ml of an aqueous solution of an antiallergic agent, diphenhydramine chloride 0.02% by mass, potassium glycyrrhetinate 0.25%, NaCl 0.1% was put into both sleeps. Itching disappeared after about 1 minute, but it became itchy again after 1 hour. The drug shed in tears and the effect did not last.
(Comparative Example 1B)
Two sugar-coated tablets containing 10 mg of diphenhydramine hydrochloride were taken. The itch disappeared after about 1 hour. However, strong sleepiness occurred. The itch recurred after about 7 hours.

(Example 2A)
A drug N3 was prepared in the same manner as in Example 1 except that 0.3 g of naphazoline hydrochloride as a vasoconstrictor and 1 g of lidocaine hydrochloride for local anesthesia were added to the purified water side when N1 was prepared. . When about 0.18 g was applied over 80-100% of the hatched portion of the nose in FIG. 3, allergic symptoms (sneezing, runny nose, nasal congestion) disappeared after about 6 minutes. Thereafter, the symptoms did not occur for about 6 hours.
(Example 2B)
After coating in Example 2A, B4 was pasted on all coated surfaces. After about 6 minutes, the symptoms disappeared. Thereafter, the symptoms did not occur for about half a day.
(Example 2C)
About 0.23 g of N3 was previously applied to B4, and this was affixed to 100% on the shaded area. After about 6 minutes, the symptom disappeared, and then the symptom did not occur for about 16 hours.
(Example 2D)
In Example 2A, the same drug N4 was prepared except that the addition amount of diphenhydramine and naphazoline hydrochloride was tripled. First, 0.18 g of glycerin was applied with a finger on the entire surface of the nose to provide the control layer. Next, 0.23 g of N4 was applied to the bond creation, and this was stuck on (100%). It took about 15 minutes for the symptoms to disappear, but the symptoms did not occur for about 1 day thereafter.
(Example 2E)
First, a bandage was put on the nose, and then it was peeled off to remove about 20% of the existing hair. Next, 0.18 g of N1 was applied over 100% of the nose. After about 4 minutes, the symptom disappeared, and then the symptom did not occur for about 6 hours.
Similarly, also in the embodiments of Examples 2B to 2D, there was an effect of the hair removal for shortening the time until the effect appeared.
(Example 2F)
First, it heated to about 50 degreeC on this nose part, the wet towel which squeezed was pressed, and the nose part was warmed. The towel was removed and a bandage heated to 47 ° C. in the same manner as that used in Example 2C was applied onto the nose. After about 4 minutes, the symptom disappeared, and then the symptom did not occur for about 16 hours.
(Example 2G)
After the treatment of Example 2A, the following treatment was further performed. About 0.1 g of N3 was applied with a finger of a hand to a region within 20 mm from the nostril entrance and a region corresponding to the dotted line in FIG. After about 5 minutes and 30 seconds, the allergic symptoms disappeared, and then the symptoms did not occur for about 6 hours.
(Example 2H)
After the treatment of Example 2G, about 0.2 g of N3 was applied to a commercially available waterproofing adhesive band excluding its peripheral part. After the palate surface was wiped with a handkerchief, it was affixed to about 70% of the first half of the palate surface. After about 5 minutes and 30 seconds, the allergic symptoms disappeared, and after about 6 hours, the symptoms did not occur, which was more comfortable than Example 2G.
Example 2I
Except for the peripheral part of the accompanying wound, 0.24 g of N4 was applied, and a 0.12 mm thick porous film was layered thereon as a control layer. This was put on the nose. Thereby, the same effect as Example 2D was acquired, without soiling a finger.
(Example 2J)
After applying the drug in Example 2A, 20 minutes later, the collodion solution was applied to 70-95% of the shaded portion of the nose using a brush. This did not occur for about half a day.
(Comparative Example 2A)
Two sugar-coated tablets containing 10 mg of diphenhydramine hydrochloride were drunk. After about 1 hour, the symptom disappeared, but strong sleepiness occurred. The symptoms recurred after about 7 hours.
(Comparative Example 2B)
Nose drops (3.3 mg of diphenhydramine hydrochloride, 0.4 mg of naphazoline hydrochloride, 3.2 mg of lidocaine hydrochloride as anhydrous, and 0.25 mg of benzethonium chloride as a bactericidal agent in 1 mL) were put in about 0 .15 mL aerosol was injected. Since the medicine is absorbed by the runny nose in the nostril and the runny nose comes out of the nose, a sufficient effect cannot be obtained. Symptoms improved after about 2 minutes when a large amount was sprayed through the nose (about 0.3 g). However, since it was washed out with a runny nose, the effect disappeared in about 3 hours.

The same thing as what was done in Examples 1 and 2 was made the same except that only the antiallergic agent was changed to equimolar amount addition of the next drug. 1) Antihistamines MCF, MJM, 2) Histamine release inhibitor pemilast, 3) Steroids betamethasone propionate, methylprednisolone.
In any of the compound experiments of 1) to 3), the effects of the present invention shown in Examples 1 and 2 were confirmed.

(Example 4A)
Except for the peripheral part of the accompanying wound, 0.16 g of N3 was applied and applied to about 80% of the inner surface within 25 mm from the entrance of the nasal cavity. After about 4 minutes, the symptoms alleviated, and for 6 hours, the symptoms did not occur.
(Example 4B)
A 0.16 g portion of N4 was applied to the accompanying wound except for its peripheral portion, and a 0.1 mm thick porous film (number of pores 300 / cm ² ) was layered thereon. This was applied to about 80% of the inner surface within 25 mm from the entrance of the nasal cavity. After about 6 minutes, the symptoms alleviated and did not occur for 1 day thereafter.
(Example 4C)
The experiment was the same as Example 4B, except that a bandage having an adhesive on both sides was used. Even better results than Example 4B were obtained. This is because the adhesive portion suppresses the passage of pollen to the back.
(Example 4D)
Experiments were performed in the same manner as in Examples 4A, 4B, and 4C, except that the spring elastic support (0.2 mm thick) was used. In each case, the effect of the example and the effect of expanding the nasal cavity cross-sectional area by 1.1 times were added, and the result was better than that of the example.
(Example 4E)
The same experiment as in Examples 4A to 4D was carried out except that EJH was replaced with the same molar amount of MCF, MJM, pemilast, and the steroid agent, and the same effect was confirmed for each compound.
(Comparative Example 4A) is the same as (Comparative Example 2B).

Represents a cross-sectional view of the human eye. Represents a human face. Represents a human face. Represents a human face. Represents human nostrils and lips. Represents a cross-sectional view of the human eye.

Explanation of symbols

1-1 represents a cross-sectional view of the eyelid.
1-2 represents a cross-sectional view of the conjunctiva of the eye.
1-3 Represents the outer surface area (shaded area) of the eyelid.
2-1 Represents the outer surface area (shaded area) of the nose.
3-1 Represents the entrance of the nostril.
3-2 A schematic view of a preferable region in which the drug A2 is brought into contact is shown.
3-3 Represents lips.
5-1 (half area on the eyeball side of the eyelid).
5-2 Represents the area of the outer surface of the eyelid.

Claims (7)

  When an allergic reaction occurs inside the eyelid of a mammal, by contacting the outer surface of the eyelid with a drug A2 containing the compound A1 that suppresses the allergic reaction or its precursor A0, When an allergic reaction occurs inside, by contacting the outer surface of the nose with a drug A2 containing the compound A1 that suppresses the allergic reaction or its precursor A0, A1 or A0 is brought into the cell from the surface. A drug containing A1 or A0 that permeates into the skin and suppresses the internal allergic reaction to 0 to 95% when there is no contact.   The inside of the eyelid represents the hatched portion in FIG. 1, and the outer surface of the eyelid is the hatched portion in FIG. 2 (below the eyebrow line, above the line 20 mm below the lower end of the eye and 20 mm away from both ends of the eye) The drug according to claim 1, which represents 5 to 100% of the area inside the line.   The inside of the nose refers to a portion between the inner surface of the nasal cavity and the outer surface of the nose, and the outer surface is a shaded portion in FIG. 3 (a portion within 22 mm from the raised end of the nose below the eyebrow line) The drug according to claim 1, which refers to an area of 5 to 100%.   The medicine according to claim 3, wherein the nasal cavity refers to a cavity existing between the nostril entrance and the upper pharynx.   4. The medicine according to claim 3, wherein the nasal cavity refers to a cavity through which air entered from a nostril entrance passes before reaching the nasopharynx.   The drug A2 according to any one of claims 1 to 5, wherein the drug A2 is a coated product obtained by applying the drug A2 on a support.   A coated product obtained by applying the drug A2 of any one of claims 1 to 5 on a support.

Images