JPS617212A - Sunscreening composition and use - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION This application is filed in the inventor's pending U.S. Patent Application No. 6
This is a continuation application of No. 14587 (filed May 29, 1984).

foot support field The present invention relates to sunscreen compositions and methods of using the same.

More particularly, the present invention relates to the preparation of esters of tocopherols and certain acids and their use in sunscreen compositions. By using the esters of the present invention, effective amounts of Provided is a method for reducing the amount of ultraviolet light reaching the skin, which comprises bringing the ester into contact with the skin as an ultraviolet absorber. , surfactant,
It can be used in compositions containing other skin treatment agents, including solvents, water, humectants, stabilizers, counterirritants, anesthetics, preservatives, and the like.

The existence of various tocopherol derivatives is known. For example, K arrer U.S. Pat.
No. 31125 (published February 1, 1941) describes stearic acid and oleic acid esters of l.copherol. Carlel is US Patent No. 22454'8
No. 0 (published on June 1, 1941) describes the introduction of allyl groups into tocopherols.

The preparation of l-copherol succinate by Baxter et al. is described in US Pat. No. 2,358,046 (issued September 12, 1944). The preparation of crystalline former-α-tocopherol p-nitrobenzoate is described in U.S. Patent No. 239313.
' No. 4 [A eschl imann
) published January 15, 1946].

A method for esterifying tocopherol using anruhalide is disclosed in U.S. Pat. No. 248654-] [Backster et al.
Baxter et al.) I 94.9 1
Published on January 1st].

A water-soluble tocopherol derivative produced by esterifying an acid ester of tocopherol with polyethylene glycol is disclosed in US Pat. No. 2,680,749 [Corey et al.
Wley et al.) June 8, 1954]
It is described in. Acid esters of tocopherols suitable for condensation with polyethylene glycol described by Coley include succinates, citraconic esters, methyl citraconic esters, itaconic esters, maleic esters, glutaconic esters and phthalic esters. Included.

Tocopherol ascorbic acid esters are produced by Spaneel (SpanelX U.S. Patent No. 315+127, 1
Published on September 29, 1964). U.S. Patent No. 3,869,477 [Schindo et al.
[Do et al., published March 4, 1975] describes the production of tocopherol p-chlorophenoxyisobutyric acid ester, and that this ester is involved in improving lipid metabolism and has an effect on arteriosclerosis. It has been reported. Vitamin A acid ester of tocopherol is disclosed in US Pat. No. 3,878,202 [Fukawa et al.
et al,)'l Published April 15, 1975]
It is described in. Cholesterol acetylsalicylic acid ester is acetylsalicylic acid ester.
ntigr+4e, Bull, soc, chi
m), 49.1852-1853 (1931)].

US Pat. No. 4,154,823 describes the use of tocopherol compounds with p-aminobenzoic acid used as one component. However, the tocopherol compound is not in the ester form. US Patent No. 414
No. 4325 describes the use of esters such as glycerol-p-aminobenzoic acid ester.

Acetylsalicylic acid ester of tocopherol is disclosed in US Pat. No. 445', a continuation of US Pat.
No. 4112 (Application No. 358557, March 1982)
(filed on May 16th).

SUMMARY OF THE INVENTION The present invention provides certain acid esters of tocopherols and their use in sunscreen compositions in which the esters act to absorb ultraviolet light. Benzoic acid esters, particularly tocopherol p-aminobenzoic acid esters, reduce the amount of UV radiation that reaches the skin when the ester is used in an effective amount, generally on the order of about 1-20% by weight of the composition in which the ester is used. Particularly useful in methods of reducing The composition can also include an inert carrier and other skin conditioning agents.

The detailed description of the invention provides certain acid esters of tocopherols as described above. A preferred tocopherol form is what is commonly referred to as alpha-tocopherol. Alpha-tocopherol may be in either natural or synthetic form. Natural vitamin E is the dextrorotary form of d-α-tocopherol, which is most preferred, while the present form is a mixture containing both the d- and levorotary Q-forms. Other tocopherols can also be used in the present invention, including the β, γ and δ forms.

The acid used to form the tocopherol ester is an acid that has an unsaturated bond conjugated to a carbonyl group. Preferred acids having this structure are aromatic acids such as substituted or unsubstituted benzoic acid.

In such acids, the unsaturated bond conjugated with the carbonyl group is a bond within the ring of the phenyl group. Nucleic acids can also have an alkenyl group between the carbonyl carbon and the phenyl,
The unsaturated bond of this alkenyl group is in a conjugated relationship with the carbonyl group. Aralkenyl groups of this type are therefore suitable for the purposes of the present invention, of which cinnamic acid is an example.

As mentioned above, aryl or phenyl groups may be substituted. Also useful are hydroxy substituents in hydroxobenzoic acid, salicylic acid or hydroxycinnamic acid, which hydroxy groups can be esterified with acetic acids such as acetic acid to form, for example, acedylsalidylic acid. When the substituent is an amino group or a substituted amino group, the nucleic acid is aminobenzoic acid and tocopherol esters of this acid are particularly useful in the present invention. Another example of a suitable acid is retinoic acid, sometimes referred to as vitamin A acid, which has a structure corresponding to vitamin A, except that the alcohol form is the acid form.

Ideally, acids suitable for forming tocopherol esters of the present invention can have the formula: AC-OH. In the formula, A is alkyl, cycloalkyl, alkaryl or aralkyl, and has an unsaturated bond conjugated with a carbonyl group.

A is preferably represented by the formula. In the formula, R has 1 carbon number
-20, preferably I-12 alkenyl, n is an integer of 0 or l, B is a substituent that does not interfere with the esterification of tocopherol, preferably argyl, amino, hydroquine or alkokyne and m is 0.112 or 3
means an integer of Alkyl, which can be denoted as R'', is preferably a short-chain alkyl having 1 to 6 carbon atoms. An amino group preferably has the formula N-R''
2[R'' is H or R'', and when both R'' are alkyl, they may be the same or different. ]. The hydroxomanocoalcogine substituent can ideally be represented by the formula ``OR''[R°'' is the same as above]. Preferred B groups are -N I-17, -N )l
CH3, -N (CH3)2, -Of-1, -〇C
IJ3, -00. It is a group selected from the group consisting of I-T5.

Preferred alkenyls I(R) are -I N -C=C- to form cinnamic acid; -c=c-c=c- to form retinoic acid with a cycloalkene group shown up to c=cc=c HHC113HI-IHC1+31-1.

As mentioned above, tocopherol p-aminobenzoic acid ester is particularly useful and the present invention is characterized by the preparation and formulation of this specific ester. However, other esters can also be prepared using conventional esterification methods, such as using nucleic acids in halide or anhydrous form.

The aminobenzoate portion of the ester can be conveniently prepared by reaction with p-nitrobenzoyl halide, particularly p-nitrobenzoyl chloride, followed by reduction of the nitro group to the amino group.

The preparation is conveniently carried out by reacting equimolar amounts of tocopherol and p-nitrobenzoyl chloride using a solvent such as pyridino. Although the nuclear reactions are conveniently carried out on an equimolar basis, an excess of either component may be used to ensure completion of the reaction. Therefore, it is often preferred to use a slight excess of tocopherol due to the fact that it is a more expensive reactant. After the reaction is complete, the solvent is removed and the product is recovered, which can be purified by crystallization from an alcohol such as isopropanol.

The product obtained is then reduced in a conventional manner using catalytic palladium and hydrogen under pressure. Nipalladium 5% carbon is the preferred catalyst and is used at 1 to 20%, preferably about 10% by weight based on the nitrobenzoate used. The pressure employed is generally greater than 50 psi. After completion of hydrogen uptake, the crude product is collected to remove the catalyst and solvent, and the product is crystallized from a solvent such as acetone to obtain the p-aminobenzoic acid ester of tocopherol.

The general method for producing esters is disclosed in Swiss Patent No. 223431 [F.
Hoffmann-La Roche & Go, )
, September 15, 1942□, Chemical Abstracts,
1949.18]0) in some detail.

As mentioned above, the esters have found use as ultraviolet absorbers, absorbing selected parts of the ultraviolet spectrum that are the primary cause of sunburn. This part of the spectrum is called American Pharmacy C.
Pharamacy), Vol, N521, No.
, May 1981, pp. 294-298], it is also called the UV-B portion. In this utility of the invention, namely UV absorption, it has been found that tocopherol p-aminobenzoic acid ester absorbs UV radiation with a maximum absorption at 298 nm. At half the absorption maximum, the wavelength at which the compound absorbs ultraviolet light is 2
84-314 nm. Therefore, the compositions of the present invention are useful for absorbing intense ultraviolet radiation having specific wavelengths. In other words, ultraviolet absorber (UV absorber)
The purpose of these methods is not to prevent the sun's ultraviolet rays from reaching the skin, but rather to prevent the sun's ultraviolet rays from reaching the skin so that the skin can build up protection through tanning in preparation for exposure to the sun. It should be noted that the purpose is to reduce the intensity.

Furthermore, it has been suggested that ultraviolet light has the ability to induce skin cancer over a substantial portion of the ultraviolet spectrum. Therefore, it is suggested that the use of the ester protects the skin from over-irradiation with ultraviolet radiation within the above-mentioned wavelength range.

It should also be noted that the use of said esters in sun protection also shows the effectiveness of tocopherols in their use as skin consistency sheets.

Thus, by using tocopherols, especially alpha-tocopherol, the skin can maintain a dismal appearance for a long time compared to untreated skin. This is particularly important considering that the tocopherol esters of the invention are used under adverse climatic conditions. That is, the compounds of the present invention provide a skin therapeutic effect due to the tocopherol portion of the molecule when used in sun protection without hindering the UV absorption action. In addition, the tocopherol esters are not easily washed off from the skin, so it is often not necessary to repeatedly apply sunscreen compositions containing tocopherol esters during sunbathing.

As mentioned above, p-aminobenzoic acid or its glycerol ester has previously been used in compositions for use as a UV absorber.

These products have certain drawbacks and adverse reactions that can be avoided by the present invention using the ester form of tocopherol. Therefore, the present invention can offer significant advantages over the use of the acid alone.

The composition of the present invention can be easily spread with a known carrier acceptable as a cosmetic and therapeutic agent, preferably an oil type carrier, having a consistency such as an emulsion, lotion, ura, wax ointment, or ointment. It is applied with sufficient command to obtain a composition that can be applied. Examples of such carriers are liquid carriers such as mineral oil, noricone oil, liquid unsaturated alcohols, liquid wax esters, branched chain fatty alcohols and triglyceride oils and mixtures thereof.

Particularly preferred for the purposes of the present invention are mineral oils or unsaturated vegetable oils which are liquid at room temperature, alone or in any desired mixtures thereof. Such oils, whose fatty acid content is at least about 50% mono- or polyunsaturated fatty acids, are rapidly absorbed into the skin, thereby transporting the essential vitamin components of the compositions of the present invention to cells damaged by sun damage. When used for contact or sun protection purposes, the absorbed or penetrated portion of the composition provides long-term protective activity against removal from the skin surface by ambient and/or mechanical factors. do. Generally, about 25 to 50 parts of such oils or mixtures thereof will provide the desired consistency, with lower viscosity being preferred when a thin, rapidly penetrating composition is desired. Examples of such ura include Almond ura, Gyounin oil, Peanut oil, Gandolnut ura, Himashi ura, L. Umo ``l Koshi ura, Cottonseed oil, Croton ura, Grape seed oil, Hagelnut oil, Hemp seed I11+, Olive oil, Momojin 411
, poppy oil, beanatsuura, bumpkin seed rl+h, safflower oil, sesame oil, soybean oil, Himawariura, walnut oil, etc.

The compositions of the invention may also contain fragrances, thickeners, diluents, preservatives, antioxidants, surfactants, colorants, organic solvents, water, stabilizers, demulcents, humectants, desiccants, irritants. Minor amounts of other known ingredients in skin treatment compositions can be included, such as anti-irritants, anesthetics, preservatives, antibiotics, anti-itch agents, lubricants, coagulants, steroids, UV absorbers, etc. . For example, about 1 to 10 parts by weight of a relatively saturated, high melting point, viscous vegetable oil, such as coconut oil, can be included to thicken and/or increase bulk.

These oils and the unsaturated vegetable oils mentioned above are also often exposed to UV light.
Has absorption properties. Also, examples include lanolin as a penetrant, lubricant and anti-drying agent, lemon ura as a fragrance and neutralizing agent, camphor as a thickening agent and viscous agent for irritation, absorption and removal of toxins from around skin cells. Small amounts of Irish moss as a lubricant, surfactants with solubilizing, emulsifying, stabilizing and/or wetting functions, and organic solvents such as water and ethanol for stabilizing, diluting, etc. can also be included.

Topical preparations usually contain small amounts of long chain alkanols. Useful long chain alkanols have about 12 to 16 carbon atoms (7, optionally with one or more carbon-carbon double bonds and one or more branched chains in the molecule. Examples of such alkanols) is oleyl alcohol, cedyl alcohol, 2
-methylundetsunonol, 2-hexyldecanol,
2-ocdyl F decanol, farnesol and phytol. Such formulations also contain hegylene glycol, diethyl glycol monostearate, glycerin [
It may also contain glycols or derivatives thereof such as 1-l and the like. lotion, emulsion,
Particularly in microemulsions, sterols such as soy sterols and alkoxy forms of the sterols such as ethoxylated phytosterols are used.

The compositions of the present invention can be prepared by any desired method and in any suitable order of addition of the various components. Those skilled in the art will readily understand mixing techniques effective for simple and efficient production of such compositions. When the composition is used, it is simply applied as a thin film or layer to the sunburned skin area or to the skin area that is to be prevented from getting sunburned or reddened, and is applied in a specific manner. The compositions of the present invention may be placed in bulk form in any suitable container and applied from the container, or may be aerated or covered, as expedient, depending on the needs of the situation. - It can also be pressurized into sol form.The preparation can be provided in the form of a solution, solution, suspension, gel, emulsion, ointment, paste or stick.

EXAMPLES The present invention will now be described in more detail with reference to Examples, but the present invention is not limited thereto. Unless otherwise specified in this specification, part or ? means parts by weight or weight 9.

Example 1 Production of p-nitrobenzoic acid ester of d-α-tocopherol A p-nitrobenzoic acid ester of d-α-tocopherol was produced according to the following recipe.

Ingredients Weight (g) d-α-tocopherol (98% purity) 50 p-nitrobenzoyl chloride 23 Pyridine 200 Dissolve α-tocopherol in pyridine and add p-nitrobenzoyl chloride all at once. The product turns reddish in color. The product is stirred for 10 minutes at room temperature, the color of the product changes to pale orange and pyridine hydrochloride is precipitated. The reaction mixture is warmed in a steam bath for 1 hour. 200 g of hexane, Then add 500 g of water. Separate the hexane layer and wash with 5% hydrochloric acid solution to remove pyridine.
% potassium carbonate solution and then water until neutral. The solvent is removed under vacuum to obtain 64.4 g (96% yield) of the crude nitrobenzoate of alpha-tocopherol.

14.5 g of this material is crystallized from olepropyl alcohol to give a lemon yellow material. The substance has a melting point (
mp) has a temperature of 64-65°C.

Example 2 Preparation of p-aminobenzoic acid ester of d-α-tocopherol A p-aminobenzoic acid ester of d-α-tocopherol was prepared according to the recipe given below.

Ingredients Weight (g) p-nitrobenzoic acid ester of d-α-tocopherol (Example 1) 49.95%
Pd on carbon 50% w/w - [Engelhand (
Engelhand)] 5.0 acetic acid
200 Hexane 50 d-α-Tocopherol p-nitrobenzoate was mixed with a mixture of hexane and acetic acid (50 g of hexane: 200 g of acid)
g). This solution and 5.0 g of catalyst are placed in a Parr vessel and reduced with hydrogen at room temperature under a pressure of 60 ps+. After 20 minutes, hydrogen absorption stops. The aminobenzoic acid ester precipitates from solution. Add acetone to dissolve the product. The catalyst is filtered off and the mother liquor is then diluted with water to precipitate the product. The resulting waxy material is suspended in isopropyl alcohol-hexane (1:1) and washed with 5% potassium carbonate and then with water until neutral.

The solvent was removed under vacuum to obtain 35.0 g (74% yield). This crude material (yellowish solid) was crystallized from acetone to yield d-α-tocopherol p-aminobenzoate as a white solid. Melting point: 164°C.

Example 3-23 = Using the product of Example 2, a representative sunscreen lotion was prepared having the following composition.

Ingredients Weight % α-tocopherol p-aminobenzoic acid ester l Oleyl alcohol IO Mineral oil
89 The resulting composition was found to be effective in reducing the amount of UV radiation reaching the skin when applied at a level of approximately 0.25 g/cm2 of skin surface.

The following is a representative starting formulation based on an oil/water sunscreen emulsion.

° Ingredients Weight % Mineral oil 20.0 Cetyl alcohol 4.0 Diethylene glycol monostearate 3.0 Ethoxylated soy sterol 5.0 Tocopherol ester 1.5 Water Add up to 100% All ingredients except water are heated to about 80°C with stirring. It is produced by heating and then adding water at 80°C. After cooling, an alcohol such as ethanol and suitable preservatives and flavors were added to obtain the desired consistency, resulting in a soft liquid creamy consistency. It is very suitable for application in tubes or squeeze containers.

Another ura/water carrier composition for topical application is a microemulsion lotion.

Ingredients Weight % Ethoxylated esterol 8.00 Tocopherol ester 5.00 Mineral oil
15.00 oleyl alcohol

Claims (1)

Claims: 1. A sunscreen composition comprising a carrier and an amount of a tocopherol ester of an acid having an unsaturated bond conjugated to a carbonyl group to reduce the amount of ultraviolet radiation reaching the skin. 2. The sunscreen composition according to claim 1, wherein the tocopherol is α-tocopherol. 3. The sunscreen composition according to claim 1, wherein the tocopherol is d-α-tocopherol. 4. The sunscreen composition according to claim 1, wherein the tocopherol is a mixture of d- and l-α-tocopherol. 5. The sunscreen composition according to claim 1, wherein the tocopherol is a mixture containing α, β, γ and δ-tocopherol as essential components. 6. The acid has the formula: ▲ Numerical formula, chemical formula, table, etc. . ] The sunscreen composition according to claim 1. 7. A is a formula: ▲ Numerical formulas, chemical formulas, tables, etc. The group and m mean an integer of 0, 1, 2 or 3. ] The composition according to claim 6, which is represented by: 8. The composition of claim 7, wherein B is selected from the group consisting of alkyl, amino, hydroxy, or alkoxy. 9, B is -NH_2, -NHCH_3, -N(CH_3
)_2, -OH, -OCH_3 and -OC_2H_5
A composition according to claim 7 selected from the group consisting of. 10. The composition according to claim 1, wherein the acid is a benzoic acid other than acetylsalicylic acid. 11. The tocopherol ester is tocopherol p-
The composition according to claim 1, which is an aminobenzoic acid ester. 12. The sunscreen composition of claim 11, wherein the tocopherol p-aminobenzoate ester is used in an amount of about 1 to 20% by weight in the sunscreen composition. 13. The sunscreen composition according to claim 1, wherein the carrier is used in an amount of 50% by weight or more in the sunscreen composition. 14. The composition of claim 1, wherein the carrier is selected from the group consisting of mineral oil, silicone oil, liquid unsaturated alcohol, liquid wax ester, branched chain aliphatic alcohol, triglyceride oil, and mixtures thereof. . 15. The composition according to claim 14, wherein the carrier is mineral oil. 16. A lotion comprising the sunscreen composition according to claim 1. 17. A microemulsion containing the sunscreen composition according to claim 1. 18. A cosmetic stick containing the sunscreen composition according to claim 1. 19. A method for reducing the amount of ultraviolet radiation reaching the skin, which comprises applying to the skin an effective sunscreen amount of a tocopherol ester of an acid having an unsaturated bond conjugated with a carbonyl group. 20. The method of claim 19, wherein the application of the tocopherol ester is carried out using an inert carrier that is non-toxic and non-irritating to the skin. 21. The method of claim 19, wherein the ester is tocopherol p-aminobenzoate, and the ester is used in the sunscreen composition in an amount of about 1 to 20% by weight. 22, d-α-tocopherol benzoate. 23, d-α-tocopherol p-aminobenzoic acid ester. 24, d-α-tocopherol p-nitrobenzoate.