AU616273B2 - Ultraviolet radiation absorbing cyclohexenylidene compositions - Google Patents

Description

II

AUSTRALIA

Patents Act COMPLETE SPECIFICATION

(ORIGINAL)

Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: 616273 Int. Class 1 Applicant(s): ICI Americas Inc New Murphy Road and Concord Pike, Wilmington, Delaware, UNITED STATES OF AMERICA Address for Service is: PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Complete Specification for the invention entitled: ULTRAVIOLET RADIATION ABSORBING CYCLOHEXENYLIDENE COMPOSITIONS Our Ref 136199 POF Code: 1453/24860 The follov-ng statement is a full description of this invention, including the best method of performing it known to applicant(s): 4n i s- 1 6006 la ULTRAVIOLET RADIATION ABSORBING CYCLOHEXENYLIDENE COMPOSITIONS The present invention is directed to ultraviolet absorbing compositions comprising substituted cyclohexenylidenes and blends thereof which are useful as protective coatings and to a method for protecting substrates against the harmful effects of actinic radiation. It is further directed to a process for making ultraviolet absorbing coating compositions.

Ultraviolet radiation absorbing coatings are useful in protecting substrates such as plastic resins ,.against accelerated deterioration and the skin of warm blooded animals against severe erythema, edema and blistering. The compositions of the invention are 4 generally referred to as sunscreen compounds and 'blends thereof can be incorporated with waxes, oils, lacquers, soft resins in the preparation of furniture and auto polishes, cosmetics, suntan oils and lotions, _20 lipsticks, hair treatments, skin formulations, contact o lenses and the like.

In particular the invention relates to sunscreen compositions comprising a carrier having incorporated therein an effective amount of a filtering agent for ultraviolet radiation selected from a 9compound of Formula I: ICI Americas Inc..

Docket No. 1717-1/2 Ai ,1

A

fel he pesen inentin isdirctedto ut44

A

-2- 2 YC/R H H-C- C -R 3 2

I

R

wherein: X and Y are independently selected from the 6 6 6 6 6 group -CN, -COOR 6

-CONHR

6

-CON(R

6 -PhCOOR 6

-COR

-C

6

H

5 -PhCOR 6 -PhN(R 6 and wherein only one X or Y e o may be substituted with and o1 2 3 4 5 S" R R R R and R are selected from the group of -OH, -COOR 6 alky, alkoxy or hydroxy- 6 alkyl groups having 1-5 carbon atoms and R is selec- 20 ted from H, alkyl, alkylaryl or arylalkyl groups of 1-22 carbon atoms.

Preferred compounds are those wherein X and

COOR

6 n

COR

6 6 i i are selected from -CN, -COOR or -COR Most preferred compounds are those wherein ".25 at least one of the X and Y groups is -CN and the other is -COOR 6 Of particular interest are compositions containing compounds of Formula I having substituent groups which provide selected absorption of actinic radiation in the 290-320nm range as well as the 320-400nm range of wavelength. The compounds may be present in the coating compositions as a finely divided solid or as a solute dispersed in an acceptable carrier when applied to a surface such that the: selection of said carrier in the coating composition permits absorbancy in the 290-400nm range.

The compositions of the invention comprise UV absorbing compounds of Formula I and others in amounts needed to provide protection against the 1-

A

V

rr i j A^ vs I e or C 0 6: *C o 6D

C

C C harmful effects of ultraviolet radiation. The amount of concentration of these compounds in the composition is such that when the composition is topically applied, the desired protection is provided. The amount needed to provide the desired protection can vary with the characteristics of the compound i.e. its extinction coefficient or substantivity, the nature of the carrier, the source and intensity of the radiation and other well recognized variables. Suitable amounts can be readily determined by standard methods of testing.

The UV filter compounds are incorporated in the carrier in an amount ranging from about 0.1% to about 50% by weight and usually in amounts of 0.5-30% by weight and preferably 1.0-15% by weight.

15 Carriers include any vehicle or medium capable of incorporating the UV filter compound in a manner permitting uniform topical application. For application on human skin, the carrier must be pharJaceutically acceptable. The term "pharmaceutically acceptable" is intended as a qualifier when the carrier is dermatologically innocuous to warm blooded animals and cosmetically acceptable, however all carriers are not useful on animal skin. The carrier may comprise a wax, oil or cream base material in which the agent can be held in a clear solution or a uniform dispersion, for example, as submicron size particles. Preferably the carrier comprises a suitable solvent or a mixture of solvents capable of dissolving the UV filter compounds to provide a concentration that is effective as a sunscreen agent when incorporated in the sunscreen formulation.

Solvents which may be useful include alcohols, ketones, esters, polyolesters such as oils, hydrocarbons, chlorinated hydrocarbons, ethers, polyethers, polyetherpolyols and other special solvents such as dimethylsulfoxide, dimethylformamide, cit Vi nr-~i-r r 1~i ~xs .Ij Iii L P 0. ,i i- 17 1 ii

A:

,1 -4dimethylisosorbide, and the like. Such solvents are considered useful only if they do not permanently interact with the active filtering agents of the invention to shift the total effective absorption outside of the 290-400nm range. Some of the above named ingredients are not pharmaceutically acceptable, but are useful in other applications.

The sunscreeening compositions may be applied as a clear liquid or as a lotion comprising a water-in-oil, an oil-in-water or a multiple emulsion.

Either the oil or water base or both may be used as a carrier for the sunscreening compositions of the S, invention. The oil base material and the water and oil base compositions will form a continuous film of 15 the UV filtering compound. Such films also provide o* protection against sun induced erythema. Sunscreening formulations are generally used in hot weather and at s beaches where people enjoy bathing activities. It is therefore desirable that the protective coating applied to the skin is not appreciably affected by 9o water or perspiration. The compositions herein disclosed are included in a thin layer protective coating on a skin of warm blooded animals and provide long lasting protection against erythema and do not appreciably decompose over practical periods of exposure to sunlight.

The cyclohexenylidenes are conveniently made by condensing acetate or malonate derivatives with an appropriate ketone in the presence of catalyst. The cyclohexenyl ketones can be synthesized by condensing 3-oxoesters with aqueous formaldehyde/dialkylamines in presence of acid catalyst. Procedures are available in the literature such as Org. Mag. Res., 15 339 (1981) and J. Chem. Soc. 1570 (1926). Representative compounds useful in the practice of the invention are i-1_ P. p listed in Table 1 which are made according to the following procedures: I) Representative Procedure for Cyanoacetate/Ketone Condensation: [Preparations 1,2,3,7,10,11,12,13,17,18,20,21 and 22] A mixture of isophorone (2,484g, 18 mol), methyl cyanoacetate (1,782g, 18 mol), acetic acid (1,080ml, 18 mol) and ammonium acetate (280g, 3.6 mol) in cyclohexane (1,500 ml) was heated at reflux for 3 hrs. with continuous removal of water through a Dean Stark trap. The reaction was cooled to room tempera- SO. ture and washed with water (1x500 ml), sat. NaHCO S. 15 (1x500 ml) and brine (1x500 ml). The organic layer was separated, dried over anhydrous Na 2

SO

4 filtered 0. 0. 2 and concentrated. Distillation of the crude reaction mixture at reduced pressure yields methyl-2-(3,5,5-trimethyl-2-cyclohexenylidene) cyanoacetate Ref: Org. Mag. Res., 1981, 15, 339 and references therein.

0 II) Representative Procedure for Amides and Amide SS. 0Dimers: [Preparation 23] A mixture of methyl 2(3,5,5-trimethyl-2cyclohexenylidene) cyanoacetate (0.2 mol), aniline (0.2 mol), sodium methoxide powder (0.22 mol) and dry t benzene (200 mls) was refluxed for 7 hours, cooled, and poured carefully into 10% HC1 (200 mls). This mixture was cooled and stirred in an ice bath while hexane (200 mls) was added. The resulting slurry was filtered, washed with water (100 mis) and hexane mis), and air dried yielding N-phenyl 2(3,5,5-tri- j methyl-2-cyclohexenylidene) cyanoacetamide.

-19- I -19- 1 1 -6- Ref: J. Org. Chem., 1963, 28, 2915 and references therein.

III) Representative Procedure for Esters and Ester Dimers: [Preparations 4-6] A mixture of methyl 2(3,5,5-trimethyl-2cyclohexenylidene) cyanoacetate (4.54 mmol), isopropanol (45.6 mmol) and LiNH 2 (0.2 g) was heated under a strong nitrogen flow in a distillation apparatus.

After 3 hrs the reaction was cooled to room temperature and neutralized with acetic acid. Ethyl acetate 0.0 (50 mls) was added and the organic phase separated, 0o washed with water (2x20 ml), sat. NaHCO 3 (1x20 ml) and 15 brine (1x10 ml), dried over MgSO 4 filtered and concentrated. Isopropyl 2(3,5,5-trimethyl-2-cyclohexenylidene) cyanjacetate was isolated by flash distillation.

Ref: U.S. pat. 3,511,812.

°00o L IV) Representative Procedure for Hydroxyesters or Hydroxyamides: [Preparation 81 Sr a •A mixture of methyl 2(3,5,5-trimethyl-2cyclohexenylidene) cyanoacetate (0.4 mol), 2,2-dimethyl-1,3-propanediol (1.8 mol), LiNH2 (0.5 g) and cyclohexane (400 mls) was refluxed under a Dean-Stark trap for 20 min. The reaction was cooled to room temperature and neutralized with acetic acid. Ethyl acetate was added, the organic phase washed with water, sat. NaHCO 3 and brine, dried over MgSO 4 filtered and 2,2-dimethyl-3-hydroxypropyl 2(3,5,5trimethyl-2-cyclohexenylidene) cyanoacetate isolated.

Ref: U.S. pat. 4,263,222.

K

/I:

I-J

V) Representative Procedure for Amides, Esters, Amide Dimers, Ester Dimers, and Mixed Amide-Ester Dimers: [Preparations 1-6, 8 and 91 2(3,5,5-trimethyl-2-cyclohexenylidene) cyanoacetic acid (0.2 mol) and thionyl chloride mis) were refluxed together for 1 hr. The acid chloride was then added dropwise with stirring to n-butylamine (0.4 mol) in petroleum ether (340 mis).

The flask may have to be cooled with an ice bath.

After addition, IN HC1 (150' ms) was added and the mixture stirred. The mixture was allowed to separate and the upper layer was washed until acid free. It was then treated with 1.4 g activated carbon, then n-butyl (3,5,5-trimethyl-2-cyclohexenylidene) cyanoacetamide was isolated.

Ref: J. Am. Chem. Soc., 1949, 71, 2215.

be C e Co

CO

0

C,.

*0 *4 *48 Ce,..

VI) Representative Procedure for Synthesis of 3- Methyl-4,6-dicarboalkoxy-2-cyclohexen-l-one: 20 Piperidine (20 ml) was added to a mixture of ethylacetoacetate (520g, 4 mol) and paraformaldehyde 2 mol). The mixture soon became very hot and it was necessary to plunge the flash into an ice-bath occasionally in order to control the reaction. After the vigorous reaction subsided the mixture was heated on the steam bath for 40 min. The yellow viscous oil (3-methyl-4,6-dicarboethoxy-2-cyclohexen-l-one) was separated from the supernatent water and dried over Na 2 SO4.

Ref: J. Am. Chem. Soc., 1943, 65, 631.

This compound condenses with ethyl cyanoacetate as in example 14 (proces- related to procedure I) to provide preparation i 1 1 h N bt;:: -I 1 1 I- 1 w" ~L -8- VII) Representative Procedure for 4- Substituted Cyclohexenones: To a mixture of methylmagnesium bromide in ether (400 ml, 0.8 mol) and FeC1 3 a solution of isophorone (83g, 0.6 mol) in ether (100 ml) was added dropwise at -20°C, and the mixture stirred for hr. TMSC1 (87g, 0.8 mol), triethylamine (60 ml), and HMPT (60 ml) were successively added at 0 C and the mixture stirred at room temperature for 24 hrs.

The mixture was poured into cold water and extracted with hexane. The extract was washed with sat'd KHSO 4 sat'd NaHCO 3 and brine, then dried over MgSO 4 The solvent was stripped and the residue distilled.

To a -60°C solution of the above silyl 15 enol-ether (20 mmol) and crotonaldehyde (24 mmol) in So CH 2 C1 2 (20 ml) was added a solution of TiC14 (20 mmol) t in CH 2 C1 2 (5 ml). After stirring for 2 hrs., the mixture was quenched with water. The CH 2 C1 2 layer was 2* stirred further with a 10% solution of adipic acid for 24 hrs. at room temperature and washed with sat'd o* NaHCO 3 and brine, then dried over MgSO 4 The solvent 1 was stripped and the residue chromatographed to yield 3,5,5-trimethyl-4-hydroxybutenyl-2-cyclohexen-l-one.

Ref: Bull. Chem. Soc. Jpn., 1982, 55, 1907.

This condenses with ethyl cyanoacetate under the 0.0 conditions of procedure I to provide compound 24.

VIII) Representative Procedure for Malonate/Ketone Condensation: [Preparation 19] A mixturj of TiC14 (5 ml) in CCl (5 ml) was added dropwise to THF (20 ml) at 0°C and under N.

Isophorone (2.9g, 21 mmol) and dimethyl malonate (3.2g, 24 rmmol) in THF (5 ml) was added dropwise, then pyridine (7.5 ml) in THF (4 ml) was added dropwise.

i I ii' a') -9- The mixture was stirred at 0°C for 30 min., then at RT for 1 hr.

The reaction was quenched with water, diluted with ether, the organic phase washed with sat'd NaHCO 3 dried, and the volatiles stripped under vacuum, then distilled to yield the diester.

The following examples serve as nonlimiting illustrations of the types of compounds included in the invention and all parts of percentages are expressed on a weight basis unless otherwise specified.

0 0 .1 t a o a 0 0 .O00.

a• e o a a 0 C0 o a a aao 00 *t o e 1 oo, e e io o• It.

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i J TABLE 1 PreD. No. R1 R2 R3 R' R' X Y X MAX tn t ft a, a a.

o a 0 Stt SQT *a ft ao a1 a a CH CH R 3 3 H H H CH H H 35 CH 3 CHi H CH3 CH3 H CHJ CH 3 B CH CHi H 3 3 CH Cli H 3 3 CH Ci H 3 3 25 CH CHi H 3 3 CH H H 3 CH 3 H H CH 3 CH 3 H CH H H CH3 CH3 1 H1 H H CH3 CH3 H H 3 CH 3 H H H Hoc CH CH H 3 3 CH3 CH H CH CH C H 3 3 47 Ci H CH3 H H Ci 3 CH 3 CH 3 CH H 3 CB H 3 CH H 3 CH H 3 CH H 3 CH H 3 CH BA Cli3 H 3 CH H 3 CH H 3 Cli 3 CH H *H H 3 Cli H 3 CHi H 3 CHi H 3 CHi H 3 CHi H 3 CN COOCH3 305 113 CN COOCH3 305 120 CN COOCH3 294 74 CN COOC5H 304 86 5 11 CN COOC H 304 94 49 CM' COOC H 304 96 37 CN C H 259,317 55.65 65 CN COOC H 0 ca.304 ca.77 5 11 CN COOC H ca.304 ca.62 10 21 CN COOC H 300 101 25 CM COOH 302.5 105 CM' COOi ca.304 Ca.118 CN COOC H ca.304 ca.103 25 CN COOC H ca.304 ca.97 25 CM COOCH 3 2 8 25 CN COC 302 129 CN CN 30 12 CN COONH ca.304 ca.127 CN COOC H ca.304 ca.110 25 COOCH3 COOCH3 284 81 CM CM 302 129 CM CN 300 122 H COO)H 274 125 CM COMPh ca.304 CM COOC H ca.304 ca.77 25 a ar aft a a ftf a a a a SQU a f'f @OQOf a a

P

i i fC.

i'F? Ref.: Ukr. Khim. Zh. (Russ. 1975, 41, 284 *(3-ethyl-2(3H)-benzothiazolylidene)methyl i; 1 iL

I

I I -11- 00 0p 00 00 frO 0U 0 *0 S 0 00 0 4 0000 I fr It has been established that the actinic radiation between 290nm and 320nm produces a substantial portion of the burning or erythema and tanning energy while the radiation between 320nm and 400nm is less erythemogenic but more tanning. The cosmetic industry has divided these spectra into the burning range UV-B (290-320nm) and the tanning range UV-A (320-400nm). Since approximately 76% of the physiological tanning potential of sunlight is found in the UV-B range and the balance is found in the UV-A range, it is desirable to have a substantial amount of the radiation in those ranges filtered out before it produces a harmful effect on the surface of human skin. While sunscreen lotions have been formulated to be most effective in the UV-B range more recent studies have indicated that it is desirable to have collective adsorption in the UV-A range as well. It has been difficult to find a practical compound which ran g e s effectively adsorbs in both4egagn. Therefore, 20 formulators must resort to the combination of two or more compounds which are each effective either in the UV-B or UV-A range to provide maximum skin protection.

Usually no one compound falling within the definition of Formula I is effective over the entire 290-400nm range and therefore either two or more compounds of Formula I can be selected and blended within the formulation of varying concentrations until the desired balance between burning and tanning is accomodated. Compounds of Formula I can be blended with sunscreening compounds from other chemical families to obtain the desired balance of protection between 290-400nm region of the UV spectrum. Such a combination is shown in Example 21. It is preferred to have a formulation having at least one compound which absorbs in the 320-400nm range. At least one can be selected from Formula I.

:i~1 £l-P~ .14 *u i; -12o 4n 4) 44 00 4 6 4 O e 44 4 4r 4 4+04 ft 0 O 04 O e0 0r w The use of the UV filters of the invention can be demonstrated 5- lotion formulations which are topically applied to the surface of the skin. The effectiveness of the UV light absorbers are tested on human subjects by treating a 1 cm square section of a subjects' back with predetermined amounts of sunscreen lotion, exposing the treated areas to UV light for a set period of time and thereafter making a visual comparison with untreated and fully masked skin areas.

The SPF (skin protection factor) is calculated by comparing the effects of radiation on protected skin with the unprotected skin.

Besides the SPF determinations on humans, many in vitro methods and in vivo tests on animal models are also widely used. Some of these methods yield results which correlate well with SPF determined on humans and are useful tools for evaluating new compounds.

The following lotions and creams will serve to illustrate but not limit those which can be used in the practice of t'e invention.

In general, typical formulating techniques are well known to skilled formulators and usually require that the filtering agent be first added to the 25 oil phase which is thereafter emulsified. With regards to examples 1-10 and controls all ingredients can be mixed together and stirred in conventional apparatus. Since in many cases a single compound used at a reasonable concentration does not effectively protect throughout the whole region of the earth reaching solar UV radiation, blends of two or more UV absorbers can be used in a formulation to afford greater protection. To illustrate the effectiveness of the compounds of the invention in sunscreen formulations, compounds of Preparations 1 and 2 were l Jj^ r -13form-u'lated into creawis and lotions for testing. The formulations of Examples 1-10 are shown in Table 2.

Examples 1-10 Blending Procedure for Examples 1, 2, 5-8: Heat mixed ingredients of to 70°C. Heat mixture B to 75 0 C then add to Add Examples 3, 4, 9 and 10 are clear solutions of Table 2 Sunscreen Formulations .1 Ingredient Examples by Weight) 1 2 3 4 5 6 7 8 9 Preparation No. 1 Preparation No. 2 Mineral Oil Stearyl Alcohol 21 Dendro Steorylether S (Brij 721 ICI Americas) 21 Dendro Steorylether (Brij 721 ICI Americas) Silicone Oil SF96 Cetyl Alcohol

(B)

Water Carbopol 934 2% sln.

(C)

o Sodium Hydroxide (10% aqueous)

(D)

(Glyco)

(E)

Dimethylisosorbide (Atlas G100) Physical Form Emulsion Solution 8 3 8 5 5 .5 .5 2.5 2.5 8 3 0 0- .5 .5 .5 1.5 1.5 2.6 1.5 1.5 2 2.5 2.5 1.4 .5 .5 .5 .5 .5 .5 70.95 75.95 71.45 70.95 75.95 71.45 10 10 10 10 10 10 .2 2 .2 .2 .2 .2 .35 .35 .35 .35 .35 .35 92 97 92 97 x x x x x x X X X X The formulation of Examples 3 and 9 were each applied to 8 specimens of excised hairless mouse 2 epidermis at a level of 1 mg/cm The epidermis was exposed to UV radiation in t' z UV-B and UV-A range and 1 6006 i~ i'~S 741 -14compared with unprotected skin similarly exposed.

Average Test results for SPF are listed in Table 3.

Table 3 Peak Mol Extinct Example Absorption Coefficient (nm) Mol. Wt.

Standard SPF Deviation UV-BTUV-A UV-B UV-A 7.32 1.32 2.89 0.145 14.0 1.73 2.2 0.164 a- I aa C C 9Se 4t 305 304 102.. 6 119 Control 100% (E) 01.0 01.0 0 Table 4 Sunscreen Formula 25 Ingredient Examples by Weight) 11 12 Control D Preparation No. 2 2 Petrolatum (Snow White USP) 35 Polyoxyethylene (21)stearyl ether 1.16 Polyoxyethylene (2)stearyl ether 3.86 Silicone Oil 3 Water (deionized) 54.08 Carbopol® 934 0.4 Sodium Hydroxide 0.4 Dowicil® 200 0.1 Physical Form cream 8 35 1.16 3.86 3 48.08 0.4 0.4 0.1 cream 0 1.16 3.86 3 56.08 0.4 0.4 0.1 cream ii 1~.

4 Additional tests on female subjects ranging from ages 27-50 having skin type I (always burns easily, never tans), type II (always burns easily, tans minimally) and type III (burns moderately, tans gradually) were performed and each subject was exposed to UV radiation on 3 separate days at 27, 28 and 29 (mW/cm 2 respectively. Templates are applied to individual skin sites on designated areas of the back.

r Application of the test material are made by uniformly spreading the lotion or cream over a 50 cm area cm by 14.3 cm) at a dose of 2mg/cm with a finger cot.

Approximately 15 minutes after application the sites were irradiated. Test sites are scored approximately 24 hours after exposure.

In addition to their use in coating skin to prevent sunburn the compositions of the invention can r also be employed in various formulations such as waxes, oils, lacquers and soft resins in the preparation of furniture and auto polishes, cosmetics, 20 lipstick, hair treatments, skin formulations and contact lenses. The compounds of the invention act as filtering agents and may be used singly or in combination to provide a wider range of protection. The following formulations are given to demonstrate a few of the many applications.

4 19 'VS -16- Example Filtering Carrier Composition No. Agent Ingredients by Wt) 13 Aerosol Hairdressing Prep 2 Decaglycerol monolaurate Polypropylene (200) monooleate Ethoxylated lanolin alcohols ,Propyleneglycol 15 Ethyl alcohol, anhydrous 39.5 EProtein polypeptide (20% alcoholic) 1.2 g Isopropyl myristate 1.3 Propellant 11 15.0 S 1 Propellant 12 30.0 Water q.s.

Procedure for Formula: Dissolve all ingredients in S 25 slightly warmed ethylalcohol, avoiding loss of the 0 alcohol, add the water, and agitate well to disperse Sany haze. Filter the concentrate and fill into aercsol containers. Add propellants.

30 14 Formula for Creamy Type Lipstick Base Prep 1 Carnauba wax 3 Candelilla wax 7 3: 5 Ozokerite@ 3 4 Beeswax 7 Lanolin Castor oil Isopropyl myristate Perfume q.s.

.w -17- Example Filtering Carrier No. Agent Ingredients Composition by Wt) Water-In-Oil Detergent Resistant, Liquid Auto Polish Part A Part B 2.00% Durmont® 500 Montan Wax (Dura Commodities) C 00 O r( r C t iCC Ct Ci CC C C o C C St C. 0 0.75% DC 530 Silicone Fluid (Dow Corning) 4.25% DC 531 Silicone Fluid 1.50% SPAN® 10.00% Kerosene 16.50% Stoddard Solvent 5.0% Preparation 1 Part C Part D 10.00% Kaopolite® SFO (Kaopolite) 50.00% Water Method of Preparation: 1. Melt wax in Part A (85-90°C) 2. Add Part B ingredients to melted wax and stir to blend well. Return temperature to 85-90°C.

3. Add Part C to Part A/Part B blend and mix until uniform with medium agitation. Keep temperature in the 85-90'C range.

4. Heat Part D to 95°C and slowly add to the blend with high speed stirring until emulsion is obtained.

Cool to 40-45°C with continuous stirring.

6. Homogenize.

r -18- Example Filtering Carrier Composition No. Agent Ingredients by Wt) 16 Neutral Base Lacquer Materials Pounds Urethane 60% N.V. 32 Long oil alkyd 60% N.V. 352 Triton X-45 Nuxtra@ Calcium 6% 12 Bentone Jell 8% 28 c Disperse the bentone jell under high speed cowles and add: Preparation 1 16 Low odor mineral sririts Cyclodex@ cobalt 6% 3 JK 270-70% 76 Water 205 .r 20 Anti skin 2 Viscosity: 80-85 KU W/G: 7.84 600 Gloss: S 25 SAG: 6 ml C It 17 O/W Paraffin Wax Emulsion 30 Part A 50% Paraffin Wax SPAN® 60/TWEEN® 60 (50/50) Preparation 2 o00* Part B 40% Water Method of Preparation: 1. Melt Part A ingredients together and heat to 80 0

C.

2. Heat Part B to 85 0

C.

3. Add Part B to Part A slowly with moderate agitation until inversion occurs. Add remaining water rapidly.

4. Cool in cold water bath with slow agitation to approximately 35 0

C.

i- If -4 -19fI Example Filtering Carrier Composition No. Agent Ingredients by Wt) 18 O/W Soft Microcrystalline Wax Emulsion Part A 30% Microcrystalline wax (Ultraflex Amber Wax-Petrolite Corp.) SPAN 60/TWEEN 60 (78/22) 5% Preparation 1 Part B 62% Water SMethod of Preparation: M t 1. Melt together Part A ingredients and S* heat to 80-90 0

C.

2. Heat Part B to boiling.

3. Add Part B to Part A slowly with 20 moderate agitation until inversion occurs. Add remaining water rapidly.

4. Remove from heat and cool to room temperature without stirring.

19 O/W Carnauba Wax Emulsion Part A 10% Carnauba wax i. 3% TWEEN 80 (ICI Americas) 30 5% Preparation 2 Part B 82% Water ea* Method of Preparation: S° 1. Melt Part A ingredients together and heat to 95 0 C and hold.

2. Heat Part B to boiling.

3. Add Part B to Part A slowly with moderately fast stirring until inversion occurs. Add remaining water rapidly.

4. Remove emulsion from heat and cool rapidly with stirring.

f® 1 I*p: 'i :jI: YlM -4 I v-f ij SUNSCREEN LOTION Example PHASE INGREDIENTS (SUPPLIERS) PERCENT BY WEIGHT t f f

C

t v

S

*6 cc e Petrolatum, Snow White USP (Ruger) Brij® 721 (ICI Americas) Brij® 72 (ICI Americas) Silicone Oil, 350cs (Ruger) Preparation 2 Uvinul M-40 (BASF) Water Carbopol® 934 F. Goodrich) Sodium Hydroxide (10% Aqueous Solution) Dowicil® 200 (DOW Chemical) 35.00 1.16 3.86 3.00 5.00 3.00 48.08 0.40 0.40 0.10 eec.

C 4 cc 4 4.

.4 4 4 44

S.

S 4 'Ce,

C

20 D (ens 'ccc Preparation: Heat to 60'C. Heat to 65 0 C. Add to slowly with moderate agitation.

Add Cool to 50 0 C. Add Cool, while stirring to

U

1 0 r.z~m~r.c~-ntr t. Wr-'

J-

-21- SUNSCREEN LOTION Example 21 PHASE INGREDIENTS (SUPPLIERS) PERCENT BY WEIGHT cc r (I 4 4 4* 9t C C

CC

0t

B

Arlamol® E (ICI Americas) Stearyl Alcohol Silicone Oil, 350 cs (Ruger) Arlasolve® 200 (ICI Americas) Brij® 72 (ICI Americas) Preparation 2 (UVB absorber) Dimethyl Ester Nophtholenzlidene Malonate (UVA absorber) Water Carbopol 934 F. Goodrich) Sodium Hydroxide (10% Aqueous Solution) Dowicil 200 (DOW) 7.00 2.50 5.00 2.10 4.90 5.00 3.00 70.00 0.20 0.20 0.10 0*#0 0 8 Preparation: Heat to 65°C. Heat to 70 0 C. Add to slowly with moderate agitation.

Add Cool to 50°C. Add Cool, while stirring to 35 0

C.

iU f 4 i -4 WdS added dropwise to THF (20 ml) at 0 0 C and under N 2 Isophorone 2 .9g, 21 mmol) and dimethyl malonate (3.2g, 24 mmol) in THF (5 ml) was added dropwise, then pyridine (7.5 ml) in THF (4 ml) was added dropwise.

;i i -22- SUNSCREEN LOTION Example 22 PHASE INGREDIENTS (SUPPLIERS) PERCENT BY WEIGHT ii (4 4 *t 0 C C4 SC i C CC I, Er 44 4 4..

4444 440 0O l Arlamol E (ICI) Stearyl Alcohol Silicone Oil, 350cs (Rugher) Arlasolve 200 (ICI) Brij 72 (ICI) Preparation 2 Water Carbopol 934 F. Goodrich) Sodium Hydroxide (10% Aqueous Solution) Dowicil 200 (DOW) 7.00 2.50 5.00 2.10 4.90 8.00 70.00 0.20

C

20 D 0.20 0.10 Preparation: Heat to 600C. Heat to 650C. Add to slowly with moderate agitation.

Add Cool to 50°C. Add 8fi~ r~~ i ji j I- I 3s- -1 .a -23- SUNSCREEN LOTION Example 23 PHASE INGREDIENTS (SUPPLIERS) PERCENT BY WEIGHT *r C Ca I

SI

I.

4o Petrolatum, Snow White USP (Ruger) Brij 721 (ICI) Brij 72 (ICI) Preparation 1 Silicone Oil, 350cs (Ruger) Water Carbopol 934 F. Goodrich) Sodium Hydroxide (10% Aqueous Solution) Dowicil 200 (DOW) 35.00 1.16 3.86 8.00 3.00 49.08 0.40 0.40 0.10 Preparation: Heat to 60 0 C. Heat to 65 0 C. Add to slowly with moderate agitation.

Add Cool to 50 0 C. Add Cool, while stirring to 350C.

r 11

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I

J

I If -24- SUNSCREEN LOTION Example 24 PHASE INGREDIENTS (SUPPLIERS) PERCENT BY WEIGHT t r 4 (4 r* Sr I I o 40 0 0 0000 0 00 0 0 0 0 0 00.4 a 4T 4 i t i (l I t 0000 0001 0 4 *00 4 ILgll 1 10

B

C

20 D Arlamol E (ICI) Stearyl Alcohol Silicone Oil, 350 cs (Ruger) Arlasolve 200 (ICI) Brij 72 (ICI) Preparation 2 Water Carbopol 934 F. Goodrich) Sodium Hydroxide (10% Aqueous Solution) Dowicil 200 (DOW) 7.00 2.50 5.00 2.10 4.90 5.50 72.50 0.20 0.20 0.10 Preparation: Heat to 65°C. Heat to 70 0 C. Add to slowly with moderate agitation.

Add Cool to 50 0 C. Add Cool, while stirring to 35 0

C.

ji: I -P Ir,

Claims (9)

1. A method for protecting a substrate against the effects of ultraviolet radiation by topically applying a composition comprising a carrier having incorporated therein an effective amount of a compound having formula I 1 2a' R R T C R Y/ RZ 515 Y 4 99 15 Y" I .20 wherein: SX and Y are independently selected from the group consisting of -CN, -COOR CONHR 6 CON(R 2 6 6 6 6 -COR 6 H 5 PhCooR PhCo, -PhN(R 2 and R 2 R3 4 R R and R are selected from the group consisting of OH, -COR 6 alkyl, alkoxy or hydroxyalkyl groups having 1-5 carbon atoms and R is selected frcm the group consisting of H, alkyl, alkylalylor arylalkyl groups of 1-22 carbon atoms, with the proviso that only one of X and Y may contain hydrogen in the R 6 position.

2. A method of Claim 1 wherein said compound are those wherein X and Y are selected from -CN, -COOR 6 or -COR 6 and incorporated in said com- Sposition in an amount ranging from about 0.1 to about 50% by weight.

3. A method of Claim 2 wherein said K compound are those wherein at least one of the X and Y groups is -CN and the other is -COOR 6 incorporated in A4/. ine rormulation or Examples 3 and 9 were each applied to 8 specimens of excised hairless mouse 2 epidermis at a level of 1 mg/cm 2 The epidermis was exposed to UV radiation in t UV-B and UV-A range and VC I i~ i -26- said composition in an amount ranging from about 15% by weight. about 1 to

4. A method of Claim 1 wherein said compound is dissolved in said carrier. A method of Claim 1 wherein said carrier is an aqueous emulsion.

6. A method of Claim 1 wherein said substrate is the skin of a warm blooded animal. g t 'I 7. A sunscreen composition comprising pharmaceutically acceptable carrier and 0.5-30% by weight of a compound selected from formula I st 2 S wherein: H-C- C R 3 2 -R 4 z y/ wherein: j_ i i: i 1 rr X and Y are independently selected from -CN, -COOR 6 -COHR 6 a -CON(R 6 ,o -CORl -C H -PC2O 6 6 6 S-PhCOR -PhN(R and 1 2 3 4 6 -OH, -COOR alkyl, alkoxy or hydroxyalkyl groups having 1-5 carbon atoms and R is selected from H, alkyl, alkylaryl or aryla'.kyl groups of 1-22 carbon atoms, with the proviso that only one of X and Y may contain hydrogen in the R 6 position. 1 2

8. A composition of Claim 7 wherein R R is CH 3 and X and Y are each -C=N and -C H 5

9. A composition of Claim 7 having at least one compound selected from Formula I and at least one other S compound which absorbs radiation in the 290-400nm range. <t t A composition of Claim 7 wherein R is selected Sfrom methyl, and -H.

11. A method of Claim 1 substantially as hereinbefore described with reference to any one of the examples.

12. A composition of Claim 7 substantially as hereinbefore described with reference to any one of the examples. t t DATED: 12 July 1991 PHILLIPS ORMONDE FITZPATRICK Attorneys for: ICI AMERICAS INC. 'De L-27- 0699L k 4 1 i