Патент USA US3030285код для вставки
United States Patent O?ice 3,030,275 Patented Apr. 17, 1962 2 1 radiation by ultraviolet irradiation, and which do not stain either the person or the clothing of the user, hav 3,030,275 ing the following structural formulae: METHOD @F PRQTEQTENG THE SKEJ FRGM ULTRAVIOLET RADIATIGN Saui hKreps, Cedar Grove, Ernst Ohisson, Summit, and Daniel Epstein, Union, Ni, assiguors to Van Dyk & Company, Inc, Believiiie, Ni, a corporation of New Jersey wherein Z is a member of a group consisting of 0X and NY2, and when Z is OX, X represents hydrogen, alkali metal, alkaline earth metal, and NH,, and when 10 Z is NY2 Y represents hydrogen, alkyl groups having 1 The present invention is directed to compositions for to 8 carbon atoms, and hydroxyl alkyl groups wherein topical application, .and more particularly to those ap the alkyl groups have 2 to 3 carbon atoms. plicable as sun-screening agents against ultra-violet rays. Among the esters which are eifective are those in which The use of sun-screening compounds in sun protective the 1,2 ~diphenylethylene- l -carboxylic acid has been preparations is well understood. The function of the esteri?ed by ethyl alcohol, isopropyl alcohol, isobutyl a1 sun screen is to absorb practically all of the erythemato cohol, methyl alcohol, glycols' or glycerol. The amides genie radiation found in sunlight before it strikes the which are effective include the simple amide, and nitro No Drawing. Filed Mar. '50, 1959, Ser. No. 302,663 2 Ciaims. (Cl. 167—%) skin of the user. This erythematogenic radiation is a gen-substituted amides. The free acid itself is also an portion of the electromagnetic radiation of the sun, and effective and stable sun-screen. extends, in the ultraviolet range from wave lengths of 20 For example, the spectrophotometric measurement of approximately 290 millimicrons to a wavelength of ap the extinction coefficient of ethyl-1,2-diphenylethylene-1 proximately 320 millimicrons. Ultraviolet radiation of carboxylate indicates that a 3 percent concentration of Wavelenght shorter than 290 millimicrons is absorbed by this material in a solution or a lotion would be ade the earth’s atmosphere and does not reach the surface quate to provide protection against painful erythema. of the earth in sui‘?cient quantity to have an erythemato 25 This is substantiated by skin tests, for when a 3 percent genie effect. Wavelengths above 320 millimicrons do (by weight) solution of the ethyl-1,2-diphenylethylene not have an appreciable erythematogenic effect, and l-carboxylate is applied to normal human skin and the hence need not be screened from the human skin in skin is exposed to the ultraviolet radiation of mid-day, order to prevent painful sunburn. On the contrary these mid-summer sunlight for four hours, no painful sun higher wavelengths result in melanin formation leading 30 burn, and no perceptible erythema results. The same to a desirably tanned skin. diphenylethylene) is a very effective sun-screening com efficient protection is afforded by solutions of, for in stance, the isobutyl ester, the methyl ester, the simple amide, the ammonium salt, the sodium salt and the po pound in the desired erythematogenic range. It has been tassium salt, as Well as by a solution of the free acid It has long been known that trans-stilbene (trans-1,2 found, however, that trans-stilbcne is readily and rapidly 35 converted by ultraviolet irradiation to the cis-stilbene isomer, which is not a good absorber of the erythemato genie radiation. This ready interconversion of the trans~ stilbene to the cis-stilbene renders the former material itself. ' It is to be understood that the concentrations of choice of the sunscreens herein described are not limited to 3% solutions or lotions. Depending upon the normal re sponse range of human skin to sunlight, and depending unsuitable for use in cosmetic sun screen preparations. 40 upon the amount of protection desired, the effective con According to spectrophotometric measurement of the ex centrations of the sunscreens may be varied over a rela tinction coe?icient of trans-stilbene, 2 percent of this r-won tively wide range. Thus, where less protection and more rapid tanning is desired, concentrations below 3% concentration to afford protection to the average human would be preferred, say .5% to 1.5%. ‘Conversely, skin against the development of a painful erythema. 45 where tanning is not desired, or for use by humans However, this observation is not substantiated by actual extraordinarily sensitive to sunlight, concentrations above material in a solution or lotion should be a sufficient use tests. Thus, when a lotion containing 2 percent 3% would be preferred, even up ‘to 6%—8%. by weight of trans-stilbcne is placed on the skin, and The 1,2-diphenylethylene-l-carboxylic acid may be the skin is exposed to the ultraviolet radiation of mid made in a variety of ways known to the art. For ex day, midsummer sunlight for four hours, a painful sun 50 ample, in a 200 cc. round bottomed ?ask, 17.4 g. (0.10 burn results. mole) of dry potassium phenylacetate, 5 g. of dry p04 The present invention is intended and adapted to over tassium carbonate (0.035 mole), 0.5 cc. pyridine, 10.6 come the de?ciencies of prior preparations of the type g. (0.10 mole) freshly distilled benzaldehyde, and 15.3 described, it being among the objects thereof to pro g. (0.15 mole) freshly distilled acetic anhydride are duce a series of eitective sun-screening compounds which 55 mixed thoroughly under nitrogen. An air-cooled re?ux are derivatives of trans-stilhene. condenser is attached and the ?ask is carefully inserted It is also among the objects of the invention to so in an oil bath at 180° C. A vigorous bubbling takes design the structure of the compounds that the effective place for a few minutes, after which the reaction pro trans-isomers of the stilbene derivatives shall be stable ceeds quietly. Heating is continued at 180-190° C. for to ultraviolet irradiation and shall not be converted to 60 two hours. The mixture is allowed to cool, and 300~400 the ineffective cis con?gurations. cc. water is added with gentle heating to break up lumps. it is a further object of the invention to prepare such Potassium hydroxide solution (6 N) is added until the ' derivatives which will not, on exposure to light and air, discolor or form other products which will discolor the person or the clothing of-the users. In practicing the present invention it has been found that salts, esters and amides of 1,2-diphenylethylene-1 carboxylic acid are ef?cient absorbers'ot erythematogenic ultraviolet radiation, which are themselves stable to it' solution is basic (about 30 cc. is required), but care should be taken not to add a large excess of base as the 65 potassium salt of the acid is easily salted out of solution. The mixture is heated until all soluble material has dis solved; sorne oily material Will remain undissolved. The ?ask is cooled under the water tap and the solution ex 3,030,275 3 A; tracted with 300-400 cc. of ether to remove unchanged benzaldehyde and a little stilbene (ca. 1 g.). The water EAMPLE 2 Hydro-Alcoholic Suntan Lotion Parts by weight solution is acidi?ed with 6 N hydrochloric acid (15-20 cc. is required), the precipitated acid ?ltered off, and the ?ltrate tested with more acid for completeness of precip Ethyl alcohol SDA No. 40 ____________________ __ 47 itation. The precipitate is conveniently dried on a porous plate in a vacuum desiccator. The crude acid melts at Propylene glycol _____________________________ __ 3 1,2-diphenylethylene carboxylic acid ____________ __ about 160° C. It is recrystallized by dissolving in 50% Color and perfume (sufficient to suit). ethanol at boiling temperature and adding Water until the solution is just cloudy. The solution is cooled very 10 3 Distilled water_ __ ___ 47 slowly, ‘and long needles form gradually. The puri?ed EXAMPLE 3 acid melts at 168—l70° C. (uncor.). The acid obtained A composition according to Example 2 in which the sun~screcning agent is partly in the form of its sodium or potassium salt, or partly in the form of its glyceryl ester. in this way is the trans-form. The simple esters of the acid are prepared by direct esteri?cation of the free acid by the appropriate alcohol 15 Any one or any combination thereof may be substituted, in the presence of an acid catalyst, such as a minor amount of sulfuric or p-toluene sulfonic acid. These es in whole or in part for the free trans-stilbene carboxylic acid. ters may then be puri?ed by distillation under high EXAMPLE 4 vacuum. The salts are made simply by dissolving the Emulsi?ed Suntan Lotion acid in a stoichiometric quantity of the desired basic 20 hydroxide or carbonate dissolved in a suitable quantity The following compositions are provided: of water or other solvent. Upon evaporation of the sol vent and concentration of the solution, the salt may be (A) obtained in essentially pure form by crystallization. The Parts by weight amides may be prepared by heating the salt of the acid 25 Mineral oil, light ___________________________ -_ 5.3 and the appropriate amine until one molecular equiv Stearic acid _______________________________ __ 6.1 alent amount of water is removed from the compound. Lanolin, anhydrous _ 2.1 The amide which is so formed may be puri?ed by crys tallization from an appropriate solvent. Another method (B) is the treatment of the acid chloride with the desired 30 Ethyl ester of 1,2-diphenylethylene-l-carhoxylic acid 3.0 amine to form the amide. Carbitol __________________________________ _ _ 4.8 Those esters of mono-, di-, and tri-hydroxy alcohols having 1 to 4 carbon atoms are particularly satisfactory (C) as Well as hydroxy alcohols, such as hydroxy ethyl and dihydroxy propyl obtained from ethylene glycol, glycerol 35 and propylene glycol. For the amines used in making amides, the aliphatic amines, primary and secondary are preferable, the alkyl groups being preferably methyl, ethyl and normal and isopropyl ‘and butyl. For alkanol amines, the mono- and di-ethanol amines and mono-iso propanol amines are preferred. Glycerine _________________________________ _ _ 2. 8 Triethanolarnine 2.0 ___________________________ _ .. Water ____________________________________ __ 73.2 Sodium alginate ____________________________ __ 0.2 The lotion is compounded according to the following procedure: Suitable formulations of ‘carriers and sunscreen agents for the application of these sun-screens to the human skin can be prepared in a variety of Ways, depending upon Heat the water and the sodium alginate to 70° C. Add the glycerine and the triethanolamine. Heat parts (A) and (C) separately to 70° C. While stirring (A), the solubility characteristics of the particular derivative of 45 slowly add (C) and continue stirring until cooled to 50° the 1,2-diphenyl-1-carhoxylic acid which is employed. C. Heat part (B) to 60° C. and add it slowly to the mix Thus, the ethyl and isobutyl esters may be dissolved in ture of (A) and (C). Continue stirring until the lotion mineral oil and be applied to the skin in this clear, oily is cooled to 40° (3., add perfume and/or color as de vehicle. The esters are also soluble in vegetable oils. sired, and package. The amides and the glycerol esters are not oil soluble, but 50 The invention is not limited to those derivatives of the are soluble in alcohol and hydro-alcoholic solution. The acid that are described herein, nor to the manner in alcohols which may be used include the ethyl and iso which the acid or its derivatives are made, or to the man propyl alcohols which are suitable for application to the ner in which the derivatives are formulated or dispensed. skin. The salts of the acids are water soluble, alcohol The‘ essence thereof is the use of such substances in sun soluble and hydro-alcohol soluble, and may be incorpo 55 tan lotions to provide long lasting protection afforded by the stability of said substances as set forth in the ap tives, and the free acid may be dissolved in appropriate pended claims. rated in clear lotions of these media. All of these deriva solvents and these solutions may be emulsi?ed to form What is claimed is: opaque emulsi?ed lotions of the water-in-oil, or the oil 1. A method of protecting the human skin from the in-water type. The emulsi?ed lotions may either be of 60 effects of exposure to ultraviolet radiation which com liquid consistency, or of the consistency of heavy pastes prises providing a cosmetic carrier, incorporating in said 0r creams. The lotions may be designed to be dispensed carrier a sunscreen agent having the formula from glass bottles, plastic squeeze bottles, or from aerosol packages, using any convenient propellant. Similarly, the clear lotions may also be packaged in a variety of ways. 65 The following are speci?c examples of sun-screening compositions containing the present compounds: wherein Z is a member of a group consisting of OX and EXAMPLE 1 Oily Suntan Lotion NY2, and when Z is OX, X represents hydrogen, alkali 70 metal, alkaline earth metal, and NH4, and when Z is Parts by weight NY2, Y represents hydrogen, alkyl groups having 1 to 8 carbon atoms, and hydroxy alkyl groups wherein the alkyl groups have 2 to v3 carbon atoms, and applying the Medicinal mineral oil _________________________ __ 97 Ethylcor isobutyl esters of 1,2-diphenylethylene car boxylic acid _______________________________ __ Color and perfume (sufficient to suit). above composition to the skin. 3 75 _ 2. A method according to claim 1 characterized in that e» e 3,080,275 6 the amount of said agent in said composition is about .5 % to 8%. References Cited in the ?le of this patent UNITED STATES PATENTS 2,104,492 pm.4: Merkel ______________ __ Jan. 4, 1938 FOREIGN PATENTS 435,811 Great Britain _________ __ Sept. 30, 1935 OTHER REFERENCES 6 Codington: J. Org. Chem, vol. 17, 1952, pp. 1027 1042. Chem. Abs., vol. 48, 1954, page 11307.