JP2012214411A - Oily formulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an odorless oily formulation containing diphenhydramine.SOLUTION: The oily formulation contains an oily base agent, diphenhydramine, and a branched unsaturated fatty acid having at least 8C in a liquid state at ordinary temperature. The amount of the branched unsaturated fatty acid having at least 8C in a liquid state at ordinary temperature contained is preferably at least 50 pts.wt., and more preferably 200 pts.wt. based on 100 pts.wt. of diphenhydramine.

Description

The present invention relates to an oil-based preparation containing diphenhydramine.

Conventionally, oily preparations based on oil components have been used as various body care products (Non-patent Document 1). More specifically, it is used for massage applications due to its smoothness (Patent Document 1), and is used for moisture retention / drying prevention applications due to its keratin occlusion effect (Patent Document 2). In particular, since oil-based preparations have an oil-based base as a main component, they have a very high effect of suppressing the evaporation of moisture from the skin, and should be used in a state called dry skin with reduced skin flexibility and elasticity. There are also many. As an inconvenience associated with dry skin such as dry skin, itching of the skin is known, and among the antihistamines, diphenhydramine is required to be added to an oily preparation.

However, diphenhydramine has a unique amine odor, and there is a problem that the odor is conspicuous if it is simply blended into an oily preparation, and it cannot be widely applied to body care products.

JP 2005-82481 A JP-A-2-15015

FRAGRANCE JOUNAL, 2010-3, 28-32

An object of the present invention is to solve the problem of odor caused by blending diphenhydramine and provide an oily preparation having an antihistamine effect.

The present invention relates to an oily preparation comprising an oily base, diphenhydramine, and a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature.

It is preferable to contain 50 parts by weight or more, more preferably 200 parts by weight or more, of a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature with respect to 100 parts by weight of diphenhydramine.

According to the present invention, since it contains a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature, it is possible to provide an oil-based preparation with less amine odor of diphenhydramine.

The oily preparation of the present invention comprises an oily base, diphenhydramine, and a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature. Here, the oil-based preparation is a substance that does not substantially contain water. “Contains substantially no water” means that the water content in the oil-based preparation is 3 g / 100 mL or less, preferably 1 g / 100 mL or less. If the water content exceeds 3 g / 100 mL, it is not preferable because many additives such as surfactants and preservatives, which may cause irritation and stinging to the skin, need to be added.

The base of the oil-based preparation of the present invention is not particularly limited as long as it is usually used in pharmaceuticals, quasi drugs, cosmetics and the like. Examples include vegetable oils, animal oils, mineral oils, lecithin derivatives, ester oils, silicones, fatty acids, higher alcohols, hormones, essential oils, silicone oils, waxes and the like. Examples of vegetable oils include olive oil, sesame oil, castor oil, wheat germ oil, rice oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, and animal oils include lard, Fish oil, squalane, beeswax and the like can be mentioned, and examples of the mineral oil include normal paraffin, isoparaffin, hydrogenated polyisobutene, liquid paraffin, light liquid paraffin, gelled hydrocarbon, petrolatum and the like. Examples of lecithin derivatives include soybean lecithin, and ester oils include isopropyl myristate, isopropyl palmitate, cetyl palmitate, diethyl sebacate, ethyl oleate, tri (capryl / caprate) glyceryl, 2-ethylhexane. Acid triglyceride (trioctanoin), hexyl laurate, dibutyl adipate, isononyl isononanoate, dicaprylyl carbonate, cetyl ethylhexanoate, ethyl hexyl palmitate, (capryl / caprate) coconut alkyl, ethyl hexyl isostearate, isostearyl palmitate, hard Fats and the like are listed. Examples of silicones include dimethylpolysiloxane and cyclic silicone. Fatty acids include oleic acid, linoleic acid, and 12-hydroxy. Such as Loki system Allyn acid, and the like. The higher alcohol is an aliphatic alcohol having 6 or more carbon atoms, and specifically includes cetanol, behenyl alcohol, myristyl alcohol, cetyl alcohol, oleyl alcohol, stearyl alcohol, lanolin alcohol, isostearyl alcohol, and the like. Examples of hormones include ethinyl estradiol, and examples of essential oils include fennel oil, clove oil, mint oil, eucalyptus oil, lemon oil, orange oil and the like. These oily bases can be used alone or in combination of two or more. Among these, a non-low polar oily base is preferable in terms of a high skin occlusion effect and a less sticky texture, and a low viscosity is preferable in terms of good elongation. Specifically, hydrocarbon-based liquid oils are preferable, such as those composed of one type such as squalane, oils in which a plurality of components such as normal paraffin, isoparaffin, liquid paraffin, and light liquid paraffin are mixed. However, the present invention is not limited to these. Among hydrocarbon liquid oils, liquid paraffin and light liquid paraffin are particularly preferable in terms of good elongation and safety.

The viscosity of the base is not particularly limited, but in the case of liquid paraffin, the SUS viscosity (Saybolt universal viscosity) at 100 ° F. is preferably 50 to 500 seconds, and more preferably 70 to 350 seconds. If it exceeds 500 seconds, the goodness of elongation decreases and the feel becomes heavy, and if it is less than 50 seconds, the keratin occlusion effect tends to decrease. Here, the Saybolt universal viscosity is a type of industrial viscosity indicated by the number of seconds that a 60 mL sample flows out of the Saybolt universal viscometer (the unit is Saybolt universal seconds). The measured temperature of 100 ° F. is converted to about 37.8 ° C.

Diphenhydramine is an antihistamine and an active ingredient that suppresses itching of the skin. Although content of diphenhydramine is not specifically limited, 0.3-3.0 g / 100 mL is preferable in an oil-based formulation, and 0.5-2.0 g / 100 mL is more preferable. If it exceeds 3.0 g / 100 mL, irritation and side effects are concerned, and if it is less than 0.3 g / 100 mL, the effect of suppressing itching tends to be insufficient.

The branched saturated fatty acid having 8 or more carbon atoms, which is liquid at normal temperature, is not particularly limited as long as it is liquid at normal temperature (20 ° C.), but low temperature stability of oil-based preparations (concerns such as precipitation of solid components and solidification of preparations) ), It must be liquid at room temperature. The number of carbon atoms is 8 or more, preferably 12 or more, and the upper limit is not particularly limited, but is preferably 22 or less. In addition, even if the fatty acid has 8 or more carbon atoms, it is necessary to lower the melting point because it becomes liquid at room temperature, and in this respect, it is necessary to have a branched structure. Since the base odor is low, it must be saturated in order to prevent odors. Specific examples include isostearic acid, hexyldecanoic acid, butyloctanoic acid and the like. Isostearic acid is an isomer of stearic acid, which is a saturated linear fatty acid having 18 carbon atoms, and has a branched structure. In external preparations, it is generally used to increase the transdermal absorbability of active ingredients, It is an ingredient used to improve the familiarity and feel to the skin. Similar fatty acids include stearic acid and oleic acid, and examples of acids used in cosmetics include phosphoric acid, lactic acid, and citric acid. However, acids such as phosphoric acid and lactic acid do not dissolve in oily formulations, and oleic acid with the same carbon number has an oxidative base odor and is not suitable for odor control, whereas isostearic acid The effect of suppressing the amine odor of diphenhydramine can be blended stably in oily preparations and is extremely excellent.

The content of the branched saturated fatty acid having 8 or more carbon atoms that is liquid at normal temperature is preferably 0.15 to 30 g / 100 mL, more preferably 0.25 to 12 g / 100 mL, and 0.4 to 8 g / 100 mL in the oily preparation. 100 mL is more preferable, and 0.5 to 6 g / 100 mL is most preferable. If it exceeds 30 g / 100 mL, the feeling when using the oil-based preparation of the present invention tends to be heavy, and if it is less than 0.15 g / 100 mL, the deodorizing effect tends to be insufficient.

The amount of the branched saturated fatty acid having 8 or more carbon atoms, which is liquid at normal temperature, is preferably 50 parts by weight or more and more preferably 100 parts by weight or more with respect to 100 parts by weight of diphenhydramine. Although an upper limit is not specifically limited, 1000 weight part or less is preferable and 600 weight part or less is more preferable. If it is less than 50 parts by weight, the deodorizing effect is not sufficient, and if it exceeds 1000 parts by weight, the feel when using the oil-based preparation of the present invention tends to be heavy.

In the oily preparation of the present invention, other components can be appropriately selected within a range not impairing the effects of the present invention, and one or more can be used in combination. For example, stabilizers, thickeners, preservatives, bactericides, buffers, pH adjusters, antipruritics, local anesthetics, anti-inflammatory agents, antihistamines, blood circulation promoters, fragrances or cooling agents, elongation improvers, vitamins Various additives, such as a kind, can be mentioned. More specifically, the following are mentioned.

Stabilizer: Dibutylhydroxytoluene, sodium edetate, sodium sulfite, dry sodium sulfite and the like.

Thickener: stearoxy hydroxypropyl methylcellulose, hydrogenated (styrene / isoprene) copolymer, hydroxypropylcellulose, xanthan gum, hypromellose (hydroxypropylmethylcellulose), carboxyvinyl polymer, sodium carboxymethylcellulose, sodium carboxymethyl starch, polyvinyl alcohol, methylcellulose, Hydroxyethyl cellulose, polyvinyl pyrrolidone, polyacrylic acid and the like.

Preservatives: butyl paraben, methyl paraben, propyl paraben, ethyl paraben, sodium benzoate, phenoxyethanol, N-coconut oil fatty acid acyl-L-arginine ethyl / DL-pyrrolidone carboxylate, benzyl alcohol and the like.

Bactericides: benzalkonium chloride, decalinium chloride, benzethonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, aqueous ammonia, sulfadiazine, triclosan, triclocarban, phenol and the like.

Buffer: borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like.

pH adjuster: organic bases such as monoethanolamine, triethanolamine, diethanolamine, diisopropanolamine, triisopropanolamine, and the like.

Antipruritics, local anesthetics: lidocaine, dibucaine, procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilucaine or their derivatives, crotamiton, benzoic acid alkyl esters (eg, ethyl aminobenzoate, parabutylaminobenzoic acid hydrochloride) Diethylaminoethyl), Tesitdecitine.

Anti-inflammatory agents, antihistamines: steroidal anti-inflammatory agents such as hydrocortisone, bradnisolone, and derivatives thereof. Non-steroidal anti-inflammatory agents such as glycyrrhetinic acid, stearyl glycyrrhetinate, licorice extract, indomethacin, diclofenac, felbinac, glycol salicylate, piroxicam and methyl salicylate. Antihistamines such as chlorpheniramine maleate, pheniramine maleate and oxatomide;

Blood circulation promoter: Vitamin E such as tocopherol acetate, nonanoic acid vanillylamide, octanoic acid vanillylamide, nicotinic acid benzyl ester, capsicoside, capsaicin, capsaicinoid, dihydroxycapsaicin, norcapsaicin, capsaicin analogs such as homocapsaicin and capsanthin, capsicum extract, Pepper-derived substances such as pepper tincture and pepper powder, hesperidin, etc.

Perfume or refreshing agent: for example, terpenes (specifically, p-menthane such as anethole, eugenol, camphor, geraniol, cineol, borneol, menthol, ryuunou, limonene, terpinolene, menthane and terpinene, and derived therefrom Monocyclic monoterpene hydrocarbon compounds, etc. These may be either d-form, l-form or dl-form), essential oils (specifically, fennel oil, cool mint oil, cinnamon oil, spearmint oil, Peppermint oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil, orange oil, etc.), isopulegol, 3-l-menthoxypropane-1,2-diol, 1- (2-hydroxydiphenyl) -4- (3- Nitrophenyl) -1,2,3,6-tetrahydroxypyrimidin-2-one, ethyl Tan carboxamide, p- menthane-3,8-diol, 3,8-dihydroxy -p- menthane -3-9- diols and trialkyl substituted cyclohexanecarboxylate A menthol-related compound such as amide or the like.

Elongation improver: Diisopropyl adipate.

Vitamins: For example, vitamin E such as vitamin A, vitamin B (other than vitamin B12), vitamin C, vitamin D, and tocopherol acetate.

Others: lactose, D-sorbitol, dibenzylidene sorbitol, polyethylene glycol (Macrogol 400, Macrogol 1500, Macrogol 4000, etc.), propylene glycol, polypropylene glycol, 1,3-butylene glycol, dipropylene glycol, soxylitol, 1 , 2-pentanediol, glycerin, 2-methyl-2,4-pentanediol and hexylene glycol, magnesium stearate, metal soap, N-acyl glutamic acid derivative, POE / POP dimethyl ether, sorbitan fatty acid ester (for example, sorbitan monostea Rate, sorbitan sesquioleate), glycerin fatty acid ester (eg, self-emulsifying glyceryl monostearate, glyceryl isooctanoate, glycerin) Monomyristate), polyglycerin fatty acid esters (eg diglyceryl monooleate, tetraglyceryl monostearate), propylene glycol fatty acid esters (eg propylene glycol monostearate) and polyoxyethylene hydrogenated castor oil (eg poly Surfactants such as oxyethylene (5) hydrogenated castor oil, polyoxyethylene (10) hydrogenated castor oil), talc, kaolin, bentonite, montmorillonite, synthetic smectite, titanium oxide, zinc oxide, anhydrous silicic acid, synthetic aluminum silicate , Nylon, silica, silylated silica, polymethyl methacrylate, polyethylene beads, silicone elastomer particles, cellulose powders and powders such as corn starch, highly polymerized polyether modified silicone Alkyl-modified silicone wax.

When mix | blending an elongation improver, 2-30 g / 100mL is preferable in an oil-based formulation, 3-15g / 100mL is more preferable, and 5-15g / 100mL is still more preferable. If it exceeds 30 g / 100 mL, the keratin occlusion effect is reduced, and if it is less than 2 g / 100 mL, the elongation tends not to be sufficiently improved.

The oily preparation of the present invention can be widely applied as a body care oil. Specifically, it can be applied to applications such as massage, moisturizing / drying prevention, itching suppression with drying, etc., and also to applications where emulsions such as creams and emulsions and ointments have been used in the past It can be suitably applied.

The present invention will be specifically described based on examples, but the present invention is not limited to these examples.

(Examples 1-10 and Comparative Examples 1-15)
According to the formulation described in Tables 1 and 2, the ingredients were mixed and liquid paraffin was added to 100 ml to obtain an oily preparation.

In addition, the following were used as a raw material.
Liquid paraffin (SUS viscosity: 350): Liquid paraffin No. 350 (manufactured by Sanko Chemical Industry Co., Ltd.)
Liquid paraffin (SUS viscosity: 70): Light liquid paraffin No. 70 (manufactured by Sanko Chemical Co., Ltd.)
Trioctanoin: NIKKOL Trifat S-308 (manufactured by Nikko Chemicals)
Diphenhydramine: Diphenhydramine (manufactured by Kongo Chemical Co., Ltd.)
Isostearic acid: Isostearic acid EX (manufactured by Higher Alcohol Industry Co., Ltd.)

The appearance and odor intensity of the obtained oily preparation were evaluated by the following methods.

(appearance)
The oily preparation was placed in a glass bottle and left overnight. The appearance of the next day was visually evaluated according to the following criteria.
◎: Colorless transparent ○: Light colored transparent ▲: Dark colored transparent or translucent ×: White turbidity or white precipitation

(Odor intensity)
Put the oily preparation in a glass bottle and leave it overnight. The odor of the head space of the next day was sensory evaluated according to the following criteria (n = 4).
5: Strong odor 4: Easily detectable odor 3: Weak odor 2: Weak odor understood by searching 1: No odor

The evaluation results are shown in Tables 1 and 2.

From the results of Table 1, when diphenhydramine is blended as in Comparative Examples 1 to 3, the odor (amine odor) becomes strong, but when isostearic acid is blended as in Examples 1 to 9, the odor is strongly suppressed. I understand. From the results of Table 2, when stearic acid, phosphoric acid, acetic acid, and citric acid are used instead of isostearic acid, the oily preparations become cloudy as shown in Comparative Examples 4-7. In oleic acid, as shown in Comparative Example 9, white turbidity was not observed, but since oleic acid itself had a base odor, not only the odor was not improved but also coloring of the preparation was observed. In addition, as for various fatty acid esters, as shown in Comparative Examples 9 to 14, there is a formulation in which almost no improvement in odor is seen, and on the contrary, there is a deterioration.

(Example: Examples 11-16 and Comparative Examples 16-20)
As the elongation improver, diisopropyl adipate was used, the blending components were mixed according to the formulation shown in Table 3, and liquid paraffin was added to 100 ml to obtain an oily preparation. Table 3 shows the results of the above-described evaluation for each preparation.

From the results in Table 3, odor can be suppressed by blending isostearic acid even in an oily preparation using diisopropyl adipate as an elongation improver (Examples 11 to 16). In addition, these oily preparations using diisopropyl adipate had improved preparation elongation compared to those not used (Examples 1 to 10), and the usability was better. On the other hand, in fatty acids and fatty acid esters such as oleic acid, isopropyl myristate, diethyl sebacate, and diisopropyl adipate, as shown in Comparative Examples 17 to 19, almost no improvement in odor was observed, and the preparation was worse There is.

Formulation Examples 1-3
According to the formulation shown in Table 4, each component was weighed, and liquid paraffin was added to 100 ml and stirred to prepare an oily preparation. Although various arbitrary components were blended, the odor was sufficiently suppressed without any clouding of the preparation.

The oily preparation of the present invention has no odor derived from diphenhydramine, which is an antihistamine, and can be suitably used for various body care products.

Claims (5)

An oily preparation comprising an oily base, diphenhydramine, and a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature. The oily preparation according to claim 1, comprising 50 parts by weight or more of a branched saturated fatty acid having 8 or more carbon atoms, which is liquid at room temperature, with respect to 100 parts by weight of diphenhydramine. The oily preparation according to claim 2, comprising 200 parts by weight or more of a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature with respect to 100 parts by weight of diphenhydramine. Furthermore, the oil-based formulation in any one of Claims 1-3 containing diisopropyl adipate. A method for suppressing odor of an oily preparation containing an oily base and diphenhydramine, wherein a branched saturated fatty acid having 8 or more carbon atoms that is liquid at room temperature is used as the odor suppressor.