JPH11189546A - Percutaneous absorption promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject promoter for promoting the absorption of a pharmacodynamic component, etc., from the skin, improving pharmacodynamic effects, reducing the amount of pharmacodynamic effects formulated, by including a polyhydric fatty acid ester and an alkyl sulfuric acid ester as active ingredients. SOLUTION: This promoter comprises (A) a polyhydric fatty acid ester (e.g. caprylic acid glycerol or the like) and (B) an alkyl sulfuric ester (e.g. sodium lauryl sulfate or the like) in the formulating ratio of 1/30 to 30/1 by weight. Preferably the objective promoter is formulated with a medicine (antipyretic analgesic such as sodium diclofenac or the like or anti angina pectoris drug such as nitroglycerin or the like) to promote absorption in a weight ratio of 1:0.01-100.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a transdermal absorption enhancer capable of promoting the absorption of medicinal components and the like from the skin, improving the medicinal effects, and reducing the amount of medicinal components to be incorporated.

[0002]

2. Description of the Related Art Conventionally, in skin external preparations such as ointments, creams and cataplasms, components exhibiting various medicinal effects by transdermal absorption are blended. However, since the skin originally has the function of preventing the invasion of foreign substances from outside the body, it is not possible to obtain sufficient transdermal absorption simply by blending a medicinal ingredient into a normal external preparation base, In many cases, sufficient medicinal effects cannot be obtained.

[0003] In order to improve percutaneous absorption of a medicinal ingredient, transdermal absorption enhancers such as isopropyl myristate and decylmethyl sulfoxide have been used in recent years. However, the effects of these transdermal absorption enhancers are not sufficiently satisfactory, and the development of a more excellent transdermal absorption enhancer has been desired.

[0004]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a percutaneous absorption enhancer having a superior percutaneous absorption promoting effect of a medicinal ingredient.

[0005]

In order to solve the above-mentioned problems, the present inventors have studied the effect of promoting percutaneous absorption of various components. When used in combination, they find that an excellent transdermal absorption promoting effect is obtained,
The present invention has been completed.

That is, the present invention provides a transdermal absorption enhancer containing polyhydric alcohol fatty acid esters and alkyl sulfates as active ingredients.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As the polyhydric alcohol fatty acid ester used in the transdermal absorption enhancer of the present invention, fatty acid esters of polyhydric alcohol having 6 to 24 carbon atoms are preferable, and polyhydric alcohol having 6 to 24 carbon atoms. Sixteen fatty acid esters are more preferred. Here, examples of the polyhydric alcohol include ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerin, polyglycerin, and sorbitan. Examples of fatty acids that form esters with these polyhydric alcohols include caproic acid, caprylic acid, capric acid, lauric acid, and myristic acid.

Among these polyhydric alcohol fatty acid esters, polyhydric alcohol monofatty acid esters are preferable, glycerin monofatty acid ester is more preferable, and glycerin mono C ₆ -C ₁₄ fatty acid ester is further preferable. As specific examples of glycerin monofatty acid ester,
Examples include glyceryl monocaproate, glyceryl monocaprylate, and glyceryl monocaprate, among which glyceryl monocaprylate is particularly preferred.

Further, as alkyl sulfates,
Alkyl sulfate salts having 6 to 24 carbon atoms are preferred,
Examples thereof include decyl sulfate, lauryl sulfate, and tetradecyl sulfate. Of these, alkali metal lauryl sulfate is more preferred, and sodium lauryl sulfate is particularly preferred.

As a combination of a polyhydric alcohol fatty acid ester and an alkyl sulfate, a combination of glyceryl monocaprylate and sodium lauryl sulfate is particularly preferred.

The blending ratio of the polyhydric alcohol fatty acid ester to the alkyl sulfate is not particularly limited,
The weight ratio is preferably 1/30 to 30/1,
10/1 is particularly preferred.

The percutaneous absorption enhancer of the present invention has a weight ratio of 0.01 to 100 to the drug to be absorbed.
It is preferable that the compounding ratio be 0.1 to 10 times, especially 0.2 to 5 times.

Examples of the drug used in the present invention include, but are not limited to, the following, and two or more of these may be blended and used as a mixture.

Antipyretic and antiphlogistic analgesics such as diclofenac sodium, indomethacin, ketoprofen, ibuprofen, etensamide, aspirin, buprenorphine hydrochloride, butorphanol tartrate, eptazosin hydrobromide, acetaminophen and the like.

Hypnotics and sedatives such as triazolam, midazolam, brotizolam, estazolam, haloxazolam, phenobarbital and the like.

Bromvalerylurea, amobarbital,
Nitrazepam, flurazepam, hydroxyzine, etizolam, clotiazepam, flutazolam, lorazepam, alprazolam, bromazepam, oxazepam, fludiazepam, mexazolam, diazepam, chlordiazepoxide, metazepam, oxazolam, flutoprazepam,
Anxiolytics such as ethyl loflazepate and prazepam.

Antipsychotics such as nortriptyline hydrochloride, amoxapine, maprotiline hydrochloride, imipramine hydrochloride, amitriptyline hydrochloride, trimipramine maleate, levomepromazine maleate, etc., clomipramine hydrochloride, lofepramine hydrochloride, doslepin hydrochloride, trazodone hydrochloride, mianserin hydrochloride, setiptiline maleate hydrochloride, Antidepressants such as safranzine.

An antipruritic such as lithium carbonate.

Dimenhydrinate, meclizine hydrochloride, diphenhydramine hydrochloride, chlorpheniramine maleate (d-form, dl-form), alimemazine tartrate, isotipendyl hydrochloride, promethazine, mequitazine, diphenylpyraline hydrochloride, clemastine fumarate, iproheptin hydrochloride, homoprone hydrochloride Antihistamines such as chlorcyclidine, cyproheptadine hydrochloride, diphenylpyrazine octoate, triprolidine hydrochloride.

Phenytoin, phenobarbital, phenobarbital sodium, metal bital, primidone, hydantol D, E, F, carbamazepine, sodium valproate, etotoin, trimetadione, ethoximide, acetylphenetride, sultiam, clonazepam, zonisamide, acetazolamide, ACTH, anti-epileptic drugs such as vitamin B _6.

Tubocurarine chloride, pancuronium bromide,
Muscle relaxants such as suxamethonium chloride, vecuronium bromide, dantrolene sodium, afrophalone, eperisone hydrochloride, chlorphenesin carbamate, baclofen, tizanidine hydrochloride, pridinol mesylate, tolperisone hydrochloride, fenprobamate, methocarbamol and the like.

Bethanechol hydrochloride, carpronium chloride,
Acetylcholine chloride, neostigmine, pyridostigmine bromide, ambenonium chloride, distigmine bromide, edphoronium chloride, atropine sulfate, scopolamine hydrobromide, butyl scopolamine bromide, N-methylscopolamine methyl sulfate, methyl anisotropine bromide, papaverine hydrochloride, iodine Oxapium bromide, baretamate bromide, piperibate hydrochloride, funnel extract, butropium bromide, trepidone, ethomidoline, metipidium bromide, tiquidium bromide, prifinium bromide, ethyl pipetanate bromide,
Autonomic nervous system drugs such as thiemonium iodide, methylbenactidium bromide, propantheline bromide, dicycloberine hydrochloride, flopropion, glucopyrronium bromide, ergometrine maleate, tofisopam, and antitussives.

Citicoline, disodium adenosine triphosphate, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, γ-oryzanol, calcium hopantenate, idebenone, meclofenoxate hydrochloride, bifemelane hydrochloride, indeloxazine hydrochloride, Lisulide maleate, aniracetam, tiapride hydrochloride, ifenprodil tartrate,
Drugs for improving cerebral circulation and metabolism such as bensicran fumarate, cinepaside maleate, vinpocetine, nicergoline, propentophylline, brovincamine fumarate, pentoxifylline, flunarizine hydrochloride, moxysilite hydrochloride, dihydroergotoxine mesylate, ozagrel sodium, and nisofenone fumarate.

Digoxin, digitoxin, methyldigoxin, deslanoside, dopamine hydrochloride, dobutamine hydrochloride,
Cardiotonic drugs such as docarpamine, denopamine, epinephrine, norepinephrine, isoprenaline hydrochloride, amnoline, carperitide, aminophylline, diprofylline, vesnarinone, pimobendan, crategus extract, trans pioxocamphor, ubitecarenone, and amino acid ethylsulfonic acid.

Nitroglycerin, amyl nitrite, isosorbite nitrate, isosorbite mononitrate, nifedipine, nicardipine hydrochloride, nilvadipine, nisoldipine, nitrendipine, manidipine hydrochloride, benidipine hydrochloride, barnidipine hydrochloride, amlodipine besylate, efonidipine hydrochloride, felodipine hydrochloride, cilanidipine hydrochloride And anti-anginal drugs such as diltiazem hydrochloride, etafenoline hydrochloride, dipyridamole, trapidil, trimetazidine hydrochloride, nicorandil and dilazeb hydrochloride.

Quinidine sulfate, procainamide hydrochloride, dizopyramide, dibenzoline succinate, bepridyl hydrochloride,
Pirmenol hydrochloride, lidocaine hydrochloride, mexiletine hydrochloride, aplindine hydrochloride, flecainide acetate, pilsicainide hydrochloride, propafenone hydrochloride, amiodarone hydrochloride, bretinium, propranol hydrochloride, bufetrol hydrochloride, bupranolol hydrochloride, bucmorol hydrochloride, timolol maleate, nadolol, pindolol, malon Poppindolol acid, oxprenol hydrochloride, alprenolol hydrochloride, indenolol hydrochloride, carteolol hydrochloride, penbutolol sulfate, bunitrolol hydrochloride, metoprolol tartrate, atenolol, bisoprolol fumarate, betaxolol hydrochloride, ceriprolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, hydrochloric acid Amosulalol, carvedilol, nipradilol, tilisolol hydrochloride, bebandrol hydrochloride, etc. Pulse for drugs.

Clonidine hydrochloride, methyldopa, guanabenz acetate, guanfacine hydrochloride, reserpine, resinamine, guanphansin sulfate, reserpine, resinamine,
Guanethidine sulfate, hexamethonium bromide, trimetaphane cansylate, prazosin hydrochloride, bunazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, hydrazine hydrochloride, captopril, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril,
Antihypertensive drugs such as benazepurine hydrochloride, imidapril hydrochloride, and temocapril hydrochloride; antihypertensive drugs such as cyclanderate, inositol hexanicotinate, cinnarizine, hepronicarte, hydralazine hydrochloride, budralazine, totrarazine hydrochloride, cadralazine, trazoline hydrochloride, isoxpurine hydrochloride, and bamethane sulfate.

Vasodilators such as cyclandate, inositol hexanicotinate, cinnarizine, hepronicat, hydralazine hydrochloride, budralazine, todralazine hydrochloride, isoxsuprine hydrochloride, and bamethane sulfate.

Clofibrate, clofibrate aluminum, clinofibrate, simfibrate, bezafibrate, nicomol, niceritol, tocofilol nicotinate, cholestyramine, probucol, pravastatin sodium, simvastatin, unsaponifiable soybean oil, purified soybean lecithin, γ-oryzanol, Drugs for treating hyperlipidemia such as oxymetholone, ethyl linoleate, sodium dextranate, esterase, and melinamide.

Dopamine hydrochloride, dobutamine hydrochloride, docarpamine, denopamine, phenylephrine hydrochloride, epinephrine, norepinephrine, isoprenaline hydrochloride, bucladecine sodium, metalaminol hydrogen tartrate, methoxamine hydrochloride, norphenephrine hydrochloride, etylefrin hydrochloride, mesyl sulfate Vasopressors such as amedinium and midodrine hydrochloride.

Dimorpholamine, dimephrine hydrochloride, doxapram hydrochloride, medroxyprogesterone, levallorphan, naloxone hydrochloride, theophylline, diprofylline,
Isoprenaline hydrochloride, isoproterol sulfate, ephedrine hydrochloride, methylephedrine hydrochloride, dl-methylephedrine saccharinate, methoxyphenamine hydrochloride, orciprenaline sulfate, chlorprenaline hydrochloride, trimethokinol hydrochloride, salbutamol sulfate, terbutaline sulfate, hexoprenaline sulfate, fumarenaline Formoterol acid, tulobuterol hydrochloride, tulobuterol, fenoterol hydrobromide, protecarol hydrochloride, clenbuterol hydrochloride, mabuterol hydrochloride, digoxin, digitoxin, methyl digoxin, lanatoside C, deslanoside,
Respiratory stimulants such as prossiladine.

Isoprenaline hydrochloride, isoproterol sulfate, ephedrine hydrochloride, methylephedrine hydrochloride, dl
-Methylephedrine saccharinate, methoxyphenamine hydrochloride, orciprenaline sulfate, chlorprenaline hydrochloride, trimethoquinol hydrochloride, salbutamol sulfate, terbutaline sulfate, hexoprenaline sulfate, formoterol fumarate, tulobuterol hydrochloride, tulobuterol, fenoterol hydrobromide, Protecalol hydrochloride, Clenbuterol hydrochloride, Mabuterol hydrochloride, Salbutamol,
Terbutaline, tulobuterol, phenothenol, procaterol, clenbuterol, thiophylline, aminophylline, choline thiophylline, diprofylline, sodium chromogrillate, tranilast, peminorast,
Ketotifen fumarate, azelastine, beclomethasone propionate, ipratropium bromide, flutropium bromide, oxitropium bromide, nifedipine, nicardipine hydrochloride, nilvadipine, nisoldipine, nitrendipine, manidipine hydrochloride, benidipine hydrochloride, balunidipine hydrochloride, amlodipine hydrochloride, emlodipine hydrochloride , Felodipine, cilnidipine, verapamil hydrochloride, diltiazem hydrochloride and other bronchodilator / asthma therapeutics.

Codeine phosphate, dihydrocodeine phosphate, noscapine, dimemorphan phosphate, tipepidine hibenzate, oxerazine citrate, guaifenesin,
Dextromethorphan hydrobromide, pentoxiverine citrate, eprazinone hydrochloride, hominoben hydrochloride, cloperastine, clofedanol hydrochloride, cherry bark extract, shazensou, asgen, kyonin water, L-methylcysteine hydrochloride, L-ethylcysteine hydrochloride, N-acetyl-L
-Antitussive expectorants such as cysteine, carbocysteine, bromhexine hydrochloride, ambroxol hydrochloride, semi-alkali proteinase, serrapeptase, bromelain, pronase, lysozyme chloride, Seihaito, ammonia fennel, senega, tyloxapol and the like.

Cimetidine, ranitidine hydrochloride, famotidine, omeprazole, lansoprazole, pirenzepine hydrochloride, proglumide, secretin, urogastone, magnesium oxide, precipitated calcium carbonate, dried aluminum hydroxide gel, magnesium aluminate metasilicate, synthetic aluminum silicate, synthetic hydrotalside, etc. Drugs for peptic ulcer.

Laxatives such as magnesium sulfate, sodium sulfate, magnesium citrate, artificial callus salts, carmellose sodium, castor oil, visacodyl, sodium picosulfate, phenovaline, senna extract, sennoside and the like.

Loperamide hydrochloride, bismuth subnitrate, albumin tannate, berberine chloride, berberine sulfate, berberine tannate, natural aluminum silicate, tyractase, β-galactosidase, mepenzolate bromide,
Antidiarrheal / intestinal medicines such as red wrinkles, salazosulfapyridine, bifidobacteria, casei bacteria, butyric acid bacteria, lactamine, resistant lactic acid bacteria, dried yeast, and dimethicone.

Bile drugs such as himechromone, anetholetrithione and osalmid.

Insulin, tolbutamide, chlorpropamide, acetohexamide, glyclopyramide, tolazamide, glibenclamide, gliclazide, glibazole,
Diabetes drugs such as buformin hydrochloride, metformin hydrochloride, acarbose, voglibose, epalrestat and the like.

Pituitary hormone drugs such as somatropin, mechaserpine, tetracosactide acetate, pituitary gonadotropin, serum gonadotropin, placental gonadotropin, vasopressin, desmopressin acetate, and oxytocin.

Cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, fludrocortisone acetate, prednisolone, prednisolone acetate,
Prednisolone butyl acetate, Prednisolone sodium succinate, Prednisolone sodium phosphate, Halopredone acetate, Methylprednisolone, Methylprednisolone acetate, Methylprednisolone sodium succinate, Triamcinolone, Triamcinolone acetate, Triamcinolone acetamide, Dexamethasone, Sodium dexamethasone, Palmitate, Palmitate A combination drug of betamethasone and betamethasone phosphate, adrenocorticotropic drugs such as betamethasone, betamethasone sodium phosphate, paramethasone acetate, and beclomethasone propionate.

Estradiol, 17β-estradiol, estradiol benzoate, estradiol dipropionate, estriol, estriol benzoate, conjugated estrogens, phosphestrol, progesterone, gestonolone caproate, norethisterone, norethisterone acetate, pregnanediol, cyproterone acetate, Sex hormone drugs or hemostatic agents such as methyltestosterone, fluoxymesterone, testosterone propionate, testosterone enanthate and drostanolone propionate.

Prostaglandin drugs such as alprostadil, beraprost sodium, gemeprost, dinoprostone, dinoprost, and dinoprost tromethamine.

Drugs for treating thyroid dysfunction, such as levothyroxine sodium, liothyronine sodium, dry thyroid, thiamazole, propylthiouracil and the like.

Retinol palmitate, alpha casidol, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, nicotinic acid, cyanocobalamin, folic acid, calcium pantothenate, ascorbic acid, tocopherol acetate,
Vitamin drugs such as bition, phytonadione, and other complex vitamins.

Complex estrogen, urokinase, tisokinase, alteplase, nasalplase, batroxobin, ticlopidine hydrochloride, cilostazol, limaprost alfadex, argatroban, ethyl icosapentate, sarpogrelate hydrochloride, heparin calcium,
Such as heparin sodium, protamine sulfate, dalteparin sodium, warfarin calcium, sodium citrate, dried and concentrated enriched human antitropin III, epoetin alfa, epoetin alfa (genetical recombination), epoetin beta, lenograstim, filgrastim, nartograstim Antithrombotic drugs.

Benzylpenicillin calcium, benzylpenicillin benzalin, pheneticillin potassium, cloxacillin sodium, flucloxacin sodium,
Ampicillin, amoxicillin, tarampicillin hydrochloride,
Ticarcillin sodium, sulbenicillin sodium,
Calinacillin sodium, piperacillin sodium,
Bipumecilin hydrochloride, sultamicillin tosylate, potassium / amoxicillin clavulanate, potassium phenoxymethylpenicillin, phenoxymethylpenicillin, benzathine, ampicillin, dicloxacillin sodium,
Oxacillin, cloxacillin, potassium clavulanate ticarcillin sodium, sulbactam sodium,
Ampicillin sodium, cephalotin sodium, cephalexin, cephamandol sodium, cefuroxy sodium, cefotaxime sodium, ceftizoxime sodium, ceftazidime, cefbuperazone sodium, latamoxef sodium, flomoxe sodium, aztreonam, carmonam sodium , Meropenem, iminepem, cilastatin sodium, panipenem, betanipron, gentamicin sulfate, kanamycin sulfate, tobramycin, fosfomycin, vancomycin hydrochloride, tetracycline hydrochloride, oxytetracycline, chloramphenicol, thianphenicol, erythromycin, kitasamycin, roxithromycin,
Antibiotics such as lincomycin hydrochloride and clindamycin.

Sulfa drugs such as sulfadiazine and silver sulfadiazine.

Antifungal drugs such as pimaricin, acyclovir, idoxuridine and the like.

Antiviral drugs such as acyclovir, amandacin, vidarabine, didanosine, zidovosine, ganciclovir, inosine pranovesque and the like.

Parasite / protozoal drugs such as quinine, sulfadoxine, pyrimethamine, metronidazole and tinidazole.

Immunosuppressants such as cyclosporine, azathioprine, mizoribine, muromonab-CD3, tacrolimus hydrate, and gusperium hydrochloride.

Blood, umbilical cord, skin tissue,
Extracts of brain, spinal cord, thymus, placenta, submandibular gland, etc.

The external preparation composition using the percutaneous absorption enhancer of the present invention preferably contains an excipient to facilitate or facilitate application to the skin. The base, stabilizer,
Preservatives, flavors, water, organic solvents, gelling agents, oils, and the like can be added as appropriate.

The excipient is not particularly limited as long as it is a pharmaceutically acceptable one usually used in pharmaceuticals or cosmetics, and it is not particularly limited, but includes lower alcohols, alcohols, and water-soluble polymers. It is preferred to use one or more of the compounds.

The lower alcohol includes, for example, ethanol, methanol, butanol, isopropyl alcohol, acetylated sucrose-modified alcohol and the like.

As the water-soluble polyhydric alcohol, for example,
Examples thereof include propylene glycol, polyethylene glycol, glycerin, 1,3-butylene glycol, and sorbitol.

Examples of the water-soluble polymer include polyvinyl alcohol, carboxyvinyl polymer, sodium polyacrylate, α · β-unsaturated carboxylic acid copolymer and / or a derivative thereof, and α · β-unsaturated Polycarboxylic acid-based crosslinked copolymer obtained by polymerizing a mixed monomer consisting of an alkali metal salt of a carboxylic acid, gelatin,
Examples include ethylene vinyl acetate copolymer resin, carrageenan, furceleran, locust bean gum, ernest gum, guar gum, gellan gum, psyllium sheet gum, hydroxypropylcellulose, hydroxypropylmethylcellulose and the like.

The form of these external preparation compositions is not particularly limited, and semisolid preparations such as ointments, creams and gels,
Patches such as cataplasms and plasters, liniments,
It may be in the form of an emulsion, a liquid such as a lotion, or an aerosol.

These external preparations for skin can be produced according to the above-mentioned various production methods, and can be used by applying to the skin, massaging as necessary, and applying the drug to the skin. Can be absorbed from the skin.

[0060]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 An experiment was carried out under the following conditions, and the cumulative permeation amount (μg / cm ² ) and permeation rate (μg / cm ² ) of indomethacin from each donor solution containing glycerin monocaprylate, sodium lauryl sulfate or both were measured. μg / cm ² / hr) and the skin permeability was compared.

Skin: Wistar male rat abdominal skin (weight: about 200 g, 8 weeks old) Apparatus: Horizontal cell capacity: 3 mL Effective area: 0.9503 cm ²
(37 ° C) Donor side; each preparation ^{* 3} (~) Receiver side: 0.05 mol / L phosphate buffer (pH
7.0) Preparation of sample solution: Every fixed time (2, 4, 6, 8, 24 hours)
After) 0.5 mL of the receiver solution is sampled. Take exactly 0.5 mL of each sample solution, 0.5 mL of IS solution
Was added accurately to obtain a sample solution, and the amount of indomethacin permeated through the skin was measured using HPLC. (IS solution: methanol solution of p-butyl benzoate in methanol; 6 μg / ml) Preparation of standard solution: Approximately 0.05 g of indomethacin is precisely weighed and dissolved by adding methanol to make exactly 50 mL.
Take exactly 1 mL of this solution and make up exactly 100 mL with phosphate buffer (pH 7.0). Further, take exactly 2 mL of this solution, add exactly 2 mL of IS solution, and use it as a standard solution.

HPLC measurement conditions Detector: UV spectrophotometer (measuring wavelength: 254 nm) Column: L-column (4.6 mm L. D. × 150 mm) Column temperature: constant temperature around 35 ° C. Mobile phase: methanol / diluted phosphorus Acid (1 → 1000) mixed solution (7: 3) Flow rate: Adjust so that the retention time of indomethacin is about 12 minutes. (0.8 ml / min) Injection volume: 10 μL * 3: Formulation A liquid obtained by suspending indomethacin in water containing 5% of glyceryl monocaprylate as an accelerator 10 mmol / l sodium lauryl sulfate as an accelerator
Indomethacin is suspended in water containing 5% glyceryl monocaprylate and 10 mmol / L sodium lauryl sulfate as a promoter. Indomethacin is suspended in water containing no promoter. Liquid (control)

FIG. 1 shows the result of the obtained cumulative transmission amount (24 hours), and FIG. 2 shows the result of the transmission speed. 1 and 2
According to the results, the skin permeability (percutaneous absorption) of indomethacin can be improved by either glycerin monocaprylate or sodium lauryl sulfate alone, but when both are used together, the effect is dramatically improved. I understand.

Example 2 1.5% by weight of a carboxylvinyl polymer and 2.0% by weight of triethanolamine were dissolved in 49% by weight of purified water, and allowed to stand for 12 hours or more to sufficiently swell the base. Separately, 3.0% by weight of ketoprofen, 3.0% by weight of glyceryl monocaprylate and 3.0% by weight of sodium lauryl sulfate are dissolved or dispersed in 40.0% by weight of ethanol, and this solution is swelled in the base. , And stirred for about 8 hours with a magnetic stirrer,
A uniform topical gel formulation was prepared.

Example 3 Except that the amount of glyceryl monocaprylate was 5.0% by weight, the amount of sodium lauryl sulfate was 5.0% by weight, and the amount of purified water was 47.0% by weight. An external gel preparation was obtained in the same manner as in Example 2.

Example 4 An external gel preparation was obtained in the same manner as in Example 2 except that ketoprofen was changed to indomethacin.

Example 5 Purified water 48 was added to a mixer set at a kneading storage temperature of 40 ° C.
% By weight, 0.1% by weight of sodium edetate, 2% by weight of light anhydrous silicic acid, and 0.3% by weight of titanium oxide were added and dissolved and dispersed in a liquid, and 1% by weight of carboxyvinyl polymer was
1.0% by weight of sodium carboxymethylcellulose was gradually added and dissolved by stirring for 10 minutes. Next, a solution in which 3.0% by weight of ketoprofen was previously dissolved or dispersed in 14% by weight of glycerin, 3.0% by weight of glycerin monocaprylate, and 3.0% by weight of sodium lauryl sulfate was added.
The mixture was stirred and dissolved for 0 minutes, and the obtained size liquid was transferred to a kneader heated to 40 ° C. Next, a solution prepared by dissolving 1% by weight of tartaric acid in 2% by weight of purified water was added thereto, and kneaded for 5 minutes. Partially neutralized product 6
The liquid in which the weight% is dispersed is gradually added and kneaded for 40 minutes.
The obtained composition was spread on a support to obtain a poultice.

Example 6 0.124 g of salbutamol sulfate was dispersed in 3.686 g of water, and 0.5 g of sodium lauryl sulfate, 0.5 g of glyceryl monocaprylate, and 0.3 g of polyvinyl pyrrolidone were used.
Add 5 g and mix. This liquid was used to prepare a methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion 1
The resulting adhesive mixture was coated on a polyester film to a thickness of 100 μm and dried to obtain a plaster having a thickness of 55 μm.

Example 7 2% by weight of propylene glycol, NIKKOR BC20T
X: 0.6% by weight; Nichol SO-10: 1.4% by weight; ethanol: 4.5% by weight; sodium lauryl sulfate: 5.0% by weight; glyceryl monocaprylate: 5.0% by weight; water: 75.5% by weight % Of D-limonene, 1.2% by weight of dimethylstearylamine and 1.2% by weight of carpronium chloride in this base.
After weight% of the solution was added with vigorous stirring using a homogenizer, the solution was placed in a plastic container with a sponge for application to obtain an external preparation.

Example 8 5% by weight of polyoxyethylene hydrogenated castor oil 60 and 30% by weight of hydrogenated rapeseed oil were heated and dissolved. After cooling, 54% by weight of isopropyl myristate was gradually added and thoroughly mixed. Then, a solution prepared by dissolving 2% by weight of ethenzamide in 2.0% by weight of sodium lauryl sulfate, 2.0% by weight of glyceryl monocaprylate, and 4.0% by weight of isopropanol is added to the mixture, and the mixture is thoroughly stirred until the whole quality becomes uniform. To obtain an ointment.

Example 9 0.3% by weight of methyl paraben was dissolved by heating in 30.1% by weight of purified water, and 2.0% by weight of betamethasone valerate, 2.0% by weight of sodium lauryl sulfate, and glycerin monocaprylate2. 0% by weight, 12.5% by weight of propylene glycol, then 2% by weight of dimethylacetamide and 1.5% by weight of sodium lauryl sulfate,
Separately, a solution prepared by heating and dissolving 25% by weight of white paraffin and 22.6% by weight of stearyl alcohol was mixed, emulsified, and cooled to obtain a cream.

Example 10 4.15% by weight of oleyl alcohol, 2.85% by weight of dimethylstearylamine, 5% by weight of diclofenac sodium, 0.5% by weight of sodium lauryl sulfate, 0.5% by weight of glycerin monocaprylate, and sorbitan fatty acid The mixture was mixed with 5% by weight of ester and 82% by weight of glycerin fatty acid ester, heated and dissolved at 70 ° C. and stirred, then dispensed into a shell-shaped mold while hot, and cooled from the outside to obtain a suppository. Was.

[0074]

The use of the transdermal absorption enhancer of the present invention can promote the absorption of various medicinal ingredients from the skin and can reduce the amount of medicinal ingredients to be incorporated.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a graph showing the cumulative permeation amount of a preparation.

FIG. 2 is a graph showing the permeation rate of the preparations.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 47/20 A61K 47/20 E

Claims (3)

[Claims] 1. A transdermal absorption enhancer comprising a polyhydric alcohol fatty acid ester and an alkyl sulfate as an active ingredient. 2. The percutaneous absorption enhancer according to claim 1, wherein the polyhydric alcohol fatty acid ester is a polyhydric alcohol monofatty acid ester, and the alkyl sulfate is an alkyl sulfate having 6 to 24 carbon atoms. 3. The percutaneous absorption enhancer according to claim 1, wherein the polyhydric alcohol fatty acid ester is glyceryl monocaprylate and the alkyl sulfate is sodium lauryl sulfate.