JPH0455165B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a topical drug composition that provides sustained release properties by increasing the adsorption of medicinal ingredients to the skin, mucous membranes, etc. and improving retention, thereby sustaining medicinal efficacy over a long period of time. It is related to. More specifically, the present invention involves blending a specific vesicle with a cationic surfactant into an aqueous medium containing a medicinal ingredient,
The present invention relates to a long-lasting topical composition with increased adsorption to mucous membranes and the like. It has been known that amphipathic substances form vesicles, that is, endoplasmic reticulum in water, and for example, vesicles such as liposomes made of phospholipids and ufasomes made of unsaturated fatty acids also exist in natural products. Since this type of vesicle is a stable dispersion, it is being applied to cosmetics, pharmaceuticals, etc. However, the naturally occurring vesicles described above are expensive, even if they have no safety issues. Therefore, it was unsuitable for mass consumption. However, recently, vesicles or niosomes using nonionic surfactants have been discovered, and the formation of vesicle dispersions using readily available raw materials, such as those with the general formula R(-OCH ₂ CHOHCH ₂ )- _o OH or (R in the formula is an aliphatic hydrocarbon group having 12 to 30 carbon atoms,
Formation of vesicles with nonionic surfactants (where n is an integer of 1 to 6) (Japanese Unexamined Patent Publication No. 1983-6375), ethylene oxide adducts of glycerin dialkyl ether and ethylene oxide adducts of myristic acid stearylamide Formation of vesicles by J.Colloid Interface
Sci., Vol. 82, No. 2, pp. 401-417). On the other hand, it is known that polyoxyethylene hydrogenated castor oil ether and polyoxyethylene sorbitol tetraoleate form concentric lamellar liquid crystals (Japanese Kagaku Zasshi, 1981, Vol.
11, pp. 1691-1696). By the way, vesicles can be said to be a special form of concentric lamellar liquid crystals, and the difference is that the surfactant forms a bimolecular membrane or multilayer membrane, and a substantial hydrophilic cavity is formed inside the vesicle.
The point is that it contains water or an aqueous solution. Therefore,
In order to form these vesicles, it is necessary that the surfactant molecules be oriented to form a lamellar bilayer film having a curvature that facilitates the formation of vesicles. However, although the polyoxyethylene hydrogenated castor oil ether forms a concentric lamellar liquid crystal, as is well known, it is a mixture of multiple compounds with different numbers of added moles of ethylene oxide; The state of the liquid crystal is not uniform, and no sharp vesicle structure is observed. The present inventors conducted various studies in order to develop a vesicle dispersion using a surfactant that is approved for use in food products, cosmetics, etc. by public institutions, and is easily available. Nonionic polyoxyethylene castor oil ether or polyoxyethylene hydrogenated castor oil ether is used as a surfactant, and by adding sorbitan polyester, a long-chain fatty acid, at a predetermined ratio, the surfactant can suppress vesicles. We found that vesicles are easily formed when oriented with a curvature that facilitates formation, and as a result of continuing research to put this vesicle into practical use, we found that this vesicle can be easily formed in the coexistence of a cationic surfactant. It has been discovered that adsorption to the skin and mucous membranes increases, and therefore, if it is incorporated into a topical preparation, it can have sustained release properties with high retention.Based on this knowledge, the present invention was made. Ivy. That is, the present invention provides (a) a cationic surfactant;
0.005 to 0.5% by weight, (b) an effective amount of medicinal ingredients, (c) (A) at least one ethoxylate selected from polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether, and ( B) Provides a long-lasting topical composition comprising 3 to 30 parts by weight of long chain fatty acid, sorbitan polyester, and vesicle dispersion per 100 parts by weight of this ethoxylate. The ethoxylate used as component (A) of the composition of the present invention is polyoxyethylene castor oil ether or polyoxyethylene hydrogenated castor oil ether, which has the general formula It has the structure shown below. These ethoxylates may be used alone or in combination of two or more, and the average number of added moles of ethylene oxide (l + m + n + x + y + z in the above formula) is 7 to 20, especially 8 to 15. range is preferred. Regarding the long-chain fatty acid sorbitan polyester used as component (B) in the vesicle dispersion of the present invention, it is preferable that the long-chain fatty acid residue has 14 to 18 carbon atoms, particularly 16 to 18 carbon atoms. Further, the degree of esterification is preferably in the range of 2.5 to 3.5, particularly preferably in the range of 2.8 to 3.2. Examples of such substances include sorbitan tripalmitate, sorbitan triolate, sorbitan tallow fatty acid triester, and the like. The ratio of component (A) and component (B) in the composition of the present invention needs to be in the range of 3 to 30 parts by weight of component (B) per 100 parts by weight of component (A), preferably 100 parts by weight.
It ranges from 5 to 100:25. When component (A) is used alone, concentric lamellar liquid crystals are formed, but no vesicle formation is observed by electron microscopy. However, when a small amount of component (B) is added, the surfactant is oriented with a curvature that facilitates the formation of vesicles, and vesicles are formed. When the ratio of component (A) to component (B) is within the above range, almost all of the aggregates formed by the surfactant used will form vesicles. Further, a preferable range is selected in consideration of the stability of the vesicle and the ability to retain various medicinal ingredients supported thereon. Further, the content of component (A) and component (B) is preferably in the range of 0.1 to 50% by weight, more preferably in the range of 1 to 35% by weight, based on the total amount of the composition. Next, in the composition of the present invention, the cationic surfactants coexisting with these vesicles include:
For example, alkylpyridium salts such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium ammonium chloride; long-chain alkylamines with 14 to 22 carbon atoms such as palmitylamine, stearylamine, and hardened tallow alkylamine; 14 carbon atoms such as palmitylamine, distearylamine, di-hardened tallow alkylamine, etc.
~22 di-long-chain alkyl amines and their salts, mono-long-chain alkyl tri-short-chain alkyl-type quaternary ammoniums, such as palmityltrimethylammonium salt, stearyltrimethylammonium salt, oleyltrimethylammonium salt, hardened beef tallow alkyltrimethylammonium salt dialkyl-type quaternary ammonium salts having two alkyl groups having 14 to 22 carbon atoms, such as distearyldimethylammonium salts, dicured beef tallow alkyldimethylammonium salts, bishydroxyethylstearylamine,
Bishydroxyethylene hardened tallow alkylamine, alkylene oxide adducts of long-chain alkylamines with 14 to 22 carbon atoms such as polyoxyethylene stearylamine, and salts thereof, quaternary products of dehydration and cyclization of stearic acid and hydroxyethylethylenediamine Examples include 2-alkyl-substituted imidazolinium salts having an alkyl group having 14 to 22 carbon atoms such as compounds. Moreover, the medicinal ingredient that can be included in the composition of the present invention is not particularly limited, and may be any medicinal ingredient that is commonly used as a medicinal ingredient in ordinary topical preparations. As such medicinal ingredients, for example, those shown below are used. (1) Disinfectants Benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine, chlorhexidine gluconate, palmityltrimethylammonium chloride, thymol,
Decanium chloride, thimerosal, markyurochrome, protein silver, chloramine, sodium hypochlorite, potassium chlorate, iodine, sodium iodide, iodine tincture, povidone-iodine,
Iodoform, oxidole, potassium permanganate, sodium perborate, ethanol, isopropanol, phenol, cresol, bithionol, acrinol, methylrosaniline chloride, nitrofurazone, resorcinol, domifuene bromide, Tego 51, biosol, chlorobutanol, salicylic acid, hexachlorophene, Benzyl alcohol, benzoic acid, creosote, acriflavine, phenyl salicylate, sodium N-lauroylsarcosine, berberine chloride, berberine sulfate. (2) Sulfur drugs homosulfamine, sulfamine, sulfisoxazole, sodium sulfisoxazole, sulfamethoxazole, sulfisomidine, sulfadiazine, sodium sulfisomidine, sodium sulfamethoxazole. (3) Local anesthetics Dibucaine hydrochloride, procaine hydrochloride, hexothiocaine hydrochloride, benzyl alcohol, ethyl aminobenzoate, benzocaine, tetracaine hydrochloride, tecaine hydrochloride, lidocaine, lidocaine hydrochloride, mepivacaine hydrochloride, pupilcaine hydrochloride,
Cocaine hydrochloride, katacaine hydrochloride, propitocaine hydrochloride, butanicaine hydrochloride, oxybutanicaine hydrochloride, meprilbutacaine hydrochloride, piperocaine hydrochloride, chlorobutanol, meprilcaine hydrochloride, epilocaine hydrochloride, thecaine. (4) Hemostatic agents, vasoconstrictors Nahuazoline nitrate, phenylecrine hydrochloride, naphazoline hydrochloride, tetrahydrozoline hydrochloride,
Oxymetazoline hydrochloride, tramazoline hydrochloride, epinephrine, thrombin, calcium gluconate, calcium chloride, calcium aspartate, cyclonamine, ferric chloride, ε-aminocaproic acid, tranexamic acid, carbazocchrome, sodium carbazocchrome sulfonate, adrenochrome mono Aminoguanidine sodium methanesulfonate, rutin, hesperidin, methylefedrin, methylefedrin hydrochloride,
hinokitiol, epidihydrocholesterin. (5) Antihistamines, antiallergic agents Crotamiton, tonzylamine hydrochloride, diphenhydramine hydrochloride, methdilazine hydrochloride, promethazine hydrochloride, diphenhydramine salicylate,
Diphenhydramine tannate, chlorpheniramine, chlorpheniramine maleate, tesitudecitin, isothipendyl hydrochloride, diphenhydramine, iproheptine hydrochloride, diphenylimidazole. (6) Antitussive and phlegm preparations, anti-asthma drugs Methyl efuedrine hydrochloride, efuedrine hydrochloride, noscapine, codeine phosphate, dextromethorphan, oxolamine, tipepidine, methyl efuedrin, isoproterenol, chlorprenaline, salbutamol, trimethoxane Nord, papaverine, aminophylline, benproperine, apomorphine, emetine, pilocarpine, thysteine, turpentine oil, eucalyptus oil, guaiacol. (7) Vitamins Lecithin, nicotinamide, ergocalciferol, calciferol, tocopherol, tocopherol acetate, ictamol, retinol acetate, retinol palmitate, pantothenyl ethyl ether, riboflavin butyrate, thiamin oil, pyridoxine dicaprylate, ascorbine acid, pyridoxine hydrochloride, riboflavin,
Calcium pantothenate, cyanocobalamin,
Vitamin A, panthenol, water-soluble vitamin A, dexpanthenol, flavin adenine dinucleotide. (8) Hormone agents Estradiol benzoate, hexestrol, methyltestosterone, testosterone propionate. (9) Cell activator Azulene, water-soluble azulene, chlorophyllin, sodium chondroitin sulfate, urea, aminoethylsulfonic acid, allantoin, potassium L-aspartate, potassium magnesium L-aspartate, chlorophyll, sodium copper chlorophyne, guarenate sodium,
Potassium guaiacol sulfonate. (10) Antibiotics Chloramphenicol, demethylchlortetracycline hydrochloride, fradiomycin sulfate, trichomycin, clotrimazole, bacitracin, colistin sulfate, colistin sodium methanesulfonate, lactobioerythromycin. (11) Non-steroidal anti-inflammatory agents glycyrrhetinic acid, flufenamic acid, mefenamic acid, indomethacin, methyl salicylate,
Glycol salicylate, dipotassium glycyrrhizinate, Glyter, phenylbutazone. (12) Steroids hydrocortisone, dexamethasone, petamethasone, prednisolone, methylprednisolone, hydrocortisone acetate, dexamethasone acetate, petamethasone walerate, triamcinolone acetonide, fluoromethasone, petamethasone. (13) Herbal medicines, Chinese herbal medicines Rosemary extract, Corydalis extract, Botanicals extract, Shinjiyu extract, Licorice extract, Amber extract, Cypress extract, Carrot extract, Chrysanthemum extract, Chamomile tincture, Ephedra extract, Ipecac extract, Chrysanthemum extract, Chrysanthemum root extract, Safflower extract, Aloe extract, Rattania tincture, myrrh extract, chinensis oil, cinnamon oil, burax extract, chinensis extract, canker extract, cypress extract,
Capsicum extract, Capsicum tincture, Arnica extract, Belladonna extract, Kouka extract,
Roto extract, sargassum tincture, hinokitiol, sansin infusion, sourdough tincture, cypress extract, eucalyptus oil, santhuron powder extract, daylily extract, rhubarb extract, the above extracts, and plant oleoresins used in tinctures. (14) Parasitic skin disease treatment agents dimazole hydrochloride, thianthol, nystatin, haloprozin, undecylenic acid, phenyl iodo undecinoate, bisdepotassium acetate, tolnaftate, griseofulvin, pyronitrin, cytucanin. (15) Enzyme preparations dextranase, lysozyme chloride, amylase, lipase, protease. (16) Local irritants camphor, d-borneol, caffein,
Menthol, tannic acid, ictamol, nonylic acid vanillylamide. (17) Agents for treating peptic ulcers: Methylmethionine sulfonium chloride, pipetanate hydrochloride, L-glutamine, isopropamide iodide, histidine hydrochloride, oxasein, sulpiride, urogastrone, suralfate, aldioxa, gelphanate, glycyrrhizin, sodium guarenate, chloride hydrochloride Benzoxamine, penthienate bromide, glycopyrronium bromide. (18) Parasympathomimetic agent neostigmine methyl sulfate. (19) Hair tonic capronium chloride. These medicinal ingredients may be used alone or
In addition, two or more types may be used in combination if necessary. In addition, as the above-mentioned cationic surfactant,
When using substances that can themselves be medicinal ingredients, such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride, a desired coating composition can be prepared without adding any other medicinal ingredients. The amount of these medicinal ingredients varies depending on the area and symptoms, but is usually based on the total amount of the composition.
It is selected within the range of 0.001 to 60% by weight. There are no particular limitations on the method for preparing the composition of the present invention, and for example, a mixture of component (A), component (B), component (a), that is, a cationic surfactant, and component (b), that is, a medicinal ingredient. Method of adding water and mixing. A method in which a mixture of the above components (A), (B), (a), and (b) is added to water and mixed. A method in which an aqueous solution in which component (B) is dissolved in advance is added to a mixture of components (A), (B), and (A) and mixed. Or in advance
In a mixture of components (A) and (B), component (A) and
This can be carried out by adding and mixing an aqueous solution containing component (b). Moreover, it can also be prepared according to an addition order other than these. The vesicle dispersion thus obtained can be diluted to any concentration as desired and used. In the composition of the present invention, substantially all of the aggregates formed by the surfactant used form vesicles, have long-term stability, are inexpensive and safe, Moreover, since it uses a surface-active substance that is easily available, it has the advantage of being extremely practical. Further, the composition of the present invention has the following characteristics, so it can be used as an open sea sterilizing disinfectant, a purulent disease treatment agent, an external analgesic, an antipruritic agent, an astringent, an antiinflammatory agent,
It is suitable as a therapeutic agent for skin diseases, an emollient, a hair agent, a dental or oral treatment agent, a nasopharyngeal liniment, an eye drop, a treatment agent for the gastrointestinal system, and the like. (1) The medicinal ingredient is retained and stabilized inside the vesicle (aqueous phase) or membrane, or both. (2) Because the membranes that make up vesicles have a structure similar to cell membranes, they have strong interaction with biological membranes and have excellent adsorption to biological tissue, and can remain on the biological surface for a relatively long time, The active ingredients incorporated into the membrane are also well absorbed into the body. (3) Because the vesicles are cationized, they have high adsorption and retention properties even in areas that are wet with blood, body fluids, water, etc., or areas where these fluids are flowing, and they can also be easily washed with water. Never leave. (4) Vesicles are more stable than emulsions (including microemulsions and multiphase emulsions), and exist stably even in dilute solutions. Vesicles are basically confirmed by observation using an electron microscope (visual judgment, photography, etc.), but they can be identified by the presence or absence of crossed Nicols under a polarizing microscope.
We can make some guesses. Next, the present invention will be explained in more detail with reference to Examples. Example 1 9 g of polyoxyethylene hydrogenated castor oil (average number of added moles of ethylene oxide: 10), 1 g of sorbitan trioleate, and 0.2 g of benzethonium chloride were mixed, and napazoline hydrochloride was added as a medicinal ingredient.
An external application composition was prepared by adding 0.1 g of dibucaine hydrochloride, 0.1 g of chlorpheniramine maleate, and 0.1 g of allantoin, and adding 10 g of ethanol and water to make a total volume of 100 ml. The composition thus obtained was diluted 50 times with water, 8.0 ml of it was taken into a test tube, 0.1 g of keratin powder was added thereto, and the mixture was shaken for 2 minutes.
The mixture was centrifuged at 3000 rpm for 5 minutes, and the content of medicinal ingredients in the supernatant was measured. Next, apply 8ml of tap water to the remaining keratin powder layer.
was added, stirred for 2 minutes, centrifuged again, and the content of medicinal ingredients in the resulting supernatant was measured. After repeating water washing and centrifugation three times in this manner, the adsorption retention amount for the keratin powder was calculated from the amount of each medicinal ingredient in each supernatant each time. On the other hand, as a control, 0.2 g of benzethonium chloride,
Nahuazoline hydrochloride 0.1g, difucaine hydrochloride 0.1g,
Prepare a solution by mixing 0.2 g of chlorpheniramine maleate, 0.1 g of allantoin, and 10 g of ethanol and diluting this with water to 100 ml. Calculate the adsorption retention amount of each medicinal ingredient on the keratin powder in the same manner as above. did. Table 1 shows the results of comparing the amount of adsorption and retention of each medicinal ingredient in the sample obtained in this way with the amount of adsorption and retention in the control.

[Table] As is clear from this table, the composition of the present invention has high adsorption and retention properties on the skin. Example 2 9 g of polyoxyethylene hydrogenated castor oil (average number of added moles of ethylene oxide: 10), 1 g of sorbitan triolate, and 0.2 g of cetylpyridium chloride were mixed, and the medicinal ingredients were 0.5 g of diphenhydramine hydrochloride and 0.1 lidocaine hydrochloride. An external application composition was prepared by adding 1.0 g of aloe vera extract and 1.0 g of aloe extract, and diluting with water until the total volume became 100 ml. A 4 cm long incision was made on the dorsal skin of 10 male Wistar rats weighing approximately 150 g, and the wound was closed using Miyutschel forceps, and approximately 2 cm of the above liniment composition was applied to the dorsal skin.
ml twice a day for 7 consecutive days to test its therapeutic effect. On the 8th day, the back skin was peeled off and the tensile strength of the cut area was measured using an Instron tensile tester. In addition, for comparison, a case without any treatment (control) and 0.2 g of cetylpyridinium chloride,
Diphenhydramine hydrochloride 0.5g, lidocaine hydrochloride
A similar test was also conducted when an aqueous solution containing only 0.1 g and 1.0 g of aloe extract was applied (comparative example). The results obtained are shown in Table 2.

[Table] As is clear from this table, healing is promoted by the application of medicinal ingredients. Next, the tensile strength of the cut portion was measured in the same manner as described above, except that each sample was washed with water 1 minute after application. The results are shown in Table 3.

[Table] As is clear from this table, the composition of the present invention has
Since it shows high retention on the skin even after washing with water, the therapeutic effect is superior to that of the comparative example. Example 3 A small amount of fragrance and saccharin were added to 9 g of polyoxyethylene hydrogenated castor oil (average number of added moles of ethylene oxide: 10), 1 g of sorbitan trioleate, 0.2 g of benzethonium chloride, and 1.0 g of rosemary extract, and then 10 g of ethanol and water were added. In addition, a mouthwash was prepared by making the total volume 100ml. After diluting the mouthwash thus obtained 40 times with 0.1M phosphate buffer (PH9), a deodorization experiment was conducted with four people who had a high amount of methyl mercaptan selected as a panel. In other words, the process of soaking 40 ml of the above diluted liquid in the subject's mouth for 15 seconds and spitting it out was 2.
After repeating this several times, the subjects were made to gargle with tap water, and three evaluators conducted a sensory evaluation of the intensity of bad breath before and after rinsing the mouth. The rating at this time was expressed as a relative intensity to the bad breath before mouthwash based on the following criteria. +2 The bad breath is much stronger than before washing the mouth. +1 〃 Strong +0.5 〃 Somewhat strong 0 〃 Normal -0.5 〃 Somewhat weak -1 〃 Weak -2 〃 Very weak The results obtained in this way are expressed as the relative strength of bad breath. It is shown in the accompanying drawing as a solid line graph showing the change over time. For comparison, a mouthwash containing neither polyoxyethylene hydrogenated castor oil nor sorbitan trioleate was prepared, and the results of a deodorization experiment conducted using this in the same manner as described above are also shown as a broken line graph. As is clear from this graph, the composition of the present invention has a high deodorizing effect and a long-lasting effect. Example 4 The amounts of each component shown in Table 4 were weighed into a 100 ml beaker and mixed well. Next, an amount of water as shown in Table 4 was added to this mixture, and the mixture was thoroughly mixed using a magnetic stirrer so as to be uniform. From Samples 1 and 2, fluid, slightly transparent, opalescent vesicle dispersions were obtained. The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle sizes were all in the range of 0.1 to 5 microns.

【table】

[Table] The dispersion thus obtained was diluted with 20 times the volume of physiological saline and used as the test solution. On the other hand, as a model of biological surface area, 4 cm ² (surface area) of the mucous membrane at the site of the golden hamster Unak pouch was peeled off. The section was washed with physiological saline, and the cheek pouch mucosa was washed with 8 ml of the test solution (the amount of flufenamic acid in the test solution was A).
mg. ) and shake for 5 minutes at 40℃. Measure the amount of flufenamic acid in the supernatant after shaking. (Defined as Bmg.) Add 4 ml of physiological saline to the cheek pouch mucosa at 40°C.
Repeat the shaking operation for 5 minutes at
mg) and the adsorption and retention amount of flufenamic acid on the cheek pouch mucosa was calculated using the following formula. Adsorption retention amount on cheek pouch mucosa = A-B-C
Table 5 shows the results of comparing the amount of flufenamic acid adsorbed and retained in the sample thus obtained with the amount of adsorption and retention in the control (Sample 3) each time.

[Table] As is clear from this table, the vesicle dispersion of sample 2 has higher adsorption to mucous membranes than sample 3 (control), and the medicinal ingredient (flufenamic acid) is released by washing, but the vesicle dispersion of sample 1 ( The present invention) has a high initial adsorption amount to mucous membranes and maintains high adsorption (retention ability) even after washing operations. Next, a formulation example of the composition of the present invention will be shown. Prescription example 1 Purulent skin disease treatment ingredient content (g) Benzethonium chloride 0.2 Sulfamethoxazole 4 Monoethanolamine 0.99 Polyoxyethylene hydrogenated castor oil (=10) 9 Sorbitan trioleate 1 Fradiomycin sulfate 1 Ethanol 10 Water Prescription example until the total amount is 100ml 2 External anti-inflammatory analgesic ingredient content (g) L-menthol 2 dl-camphor 2 Thymol 0.5 Trophiechol acetate 0.2 Methyl salicylate 3 Glycol salicylate 1 Benzalkonium chloride 0.1 Capsicum extract 0.25 Polyoxy Ethylene hydrogenated castor oil (=10) 9 Sorbitan trioleate 1 Ethanol 30 Water Prescription example until total volume is 100ml 3 Parasitic skin disease treatment ingredient content (g) Clotrimazole 1 Benzalkonium chloride 0.2 Polyoxyethylene hardening Castor oil (=10) 9 Sorbitan trioleate 1 Ethanol 10 Water Prescription example until total volume is 100ml 4 Hair agent ingredient content (g) Estradiol benzoate 0.001 Hydrocortisone 0.0016 Capronium chloride 0.5 Polyoxyethylene hydrogenated castor oil (=10 ) 9 Sorbitan trioleate 1 Benzalkonium chloride 0.02 Ethanol 10 Water Prescription example until total volume is 100ml 5 Disinfectant ingredient content (g) Benzethonium chloride 0.2 Lysozyme chloride 0.5 Polyoxyethylene hydrogenated castor oil (=10) 9 Sorbitan Trioleate 1 Ethanol 10 Water Prescription example until the total amount is 100ml 6 Mouthwash ingredient content (g) Benzethonium chloride 0.2 Sodium guarenate 0.3 L-menthol 0.6 Thymol 0.1 d-borneol 0.1 Ascorbic acid 0.2 Chlorpheniramine maleate 0.2 Methylphedrin hydrochloride 0.2 Polyoxyethylene hydrogenated castor oil (=10) 9 Sorbitan trioleate 1 Ethanol 10 Water Dilute this 20 times with water until the total volume is 100 ml. Prescription example 7 Nasopharyngeal liniment ingredient content (g) Naphazoline hydrochloride 0.05g Dipotassium glycyrrhizylate 0.3 Lysozyme chloride 0.5 Procaine hydrochloride 0.1 Benzalkonium chloride 0.02 Polyoxyethylene hydrogenated castor oil (=10) 9 Sorbitan trioleate 1 Ethanol 10 Water Prescription example until total volume is 100ml 8 Eye drops A ingredient content (g) Benzalkonium chloride 0.01 Flavin adenine dinucleotide 0.02 Sulfamethoxazole 4 Monoethanolamine 0.99 Neostigmine methyl sulfate 0.002 Polyoxyethylene hydrogenated castor oil ( =10) 3 Sorbitan trioleate 0.3 Water Prescription example until the total amount is 100ml 9 Eye drops B component content (g) Benzalkonium chloride 0.01 Fluorometholone 0.1 Polyoxyethylene hydrogenated castor oil (=10) 3 Sorbitan trioleate 0.3 Boric acid 1.5 Water Prescription example until total volume is 100ml 10 Eye drops C component content (g) Benzalkonium chloride 0.01 Erythromycin lactobionate 0.5 Colistin sodium methanesulfonate 0.5 Polyoxyethylene hydrogenated castor oil (=10) 3 Sorbitan triole ate 0.3 Water Prescription example until total volume is 100ml 11 Gastrointestinal drug ingredient content (g) Benzalkonium chloride 0.05 Methylmethionine sulfonium chloride 0.5 Glycyrrhizin 0.7 Sodium copper chlorophine 0.1 Polyoxyethylene hydrogenated castor oil (=10) 9 Sorbitan triole Et 1 Water Until the total volume reached 100 ml No separation of the vesiculating agent was observed in any of the formulation examples described above, indicating good stability.

[Brief explanation of the drawing]

The drawing is a graph showing the deodorizing effects of the mouthwash according to the present invention and a conventional mouthwash.

Claims (1)

[Claims] 1 (a) 0.005 to 0.5% by weight of a cationic surfactant;
(b) an effective amount of a medicinal ingredient; and (c) at least one selected from (A) polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether.
ethoxylate of the species and (B) this ethoxylate.
3 to 30 parts by weight per 100 parts of a vesicle dispersion of sorbitan polyester of long-chain fatty acids. 2 Component (A) has an average number of added moles of ethylene oxide of 7
Claim 1 which is an ethoxylate of ~20
The long-acting topical composition described in Section 1. 3. The long-acting topical composition according to claim 1, wherein component (B) is a sorbitan polyester of a long chain fatty acid having 16 to 18 carbon atoms.