US3625976A - Coumarin ether sun-screening compounds - Google Patents
Coumarin ether sun-screening compounds Download PDFInfo
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- US3625976A US3625976A US883239A US88323969A US3625976A US 3625976 A US3625976 A US 3625976A US 883239 A US883239 A US 883239A US 88323969 A US88323969 A US 88323969A US 3625976 A US3625976 A US 3625976A
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- US
- United States
- Prior art keywords
- compounds
- coumarin
- sun
- carbon atoms
- methyl
- Prior art date
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- Expired - Lifetime
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 52
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title abstract description 24
- 235000001671 coumarin Nutrition 0.000 title abstract description 16
- 229960000956 coumarin Drugs 0.000 title abstract description 15
- 238000012216 screening Methods 0.000 title description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title description 6
- 239000000203 mixture Substances 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims 1
- -1 alkadienyl Chemical group 0.000 abstract description 17
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 239000000516 sunscreening agent Substances 0.000 abstract description 7
- 125000001485 cycloalkadienyl group Chemical group 0.000 abstract description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract description 6
- 231100000344 non-irritating Toxicity 0.000 abstract description 6
- 230000009965 odorless effect Effects 0.000 abstract description 6
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 abstract description 4
- 125000005082 alkoxyalkenyl group Chemical group 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 125000002877 alkyl aryl group Chemical group 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 33
- 230000008859 change Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 150000001649 bromium compounds Chemical class 0.000 description 7
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Inorganic materials [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001805 chlorine compounds Chemical class 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 230000000475 sunscreen effect Effects 0.000 description 5
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Chemical compound CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- VYBREYKSZAROCT-UHFFFAOYSA-N alpha-myrcene Natural products CC(=C)CCCC(=C)C=C VYBREYKSZAROCT-UHFFFAOYSA-N 0.000 description 2
- 238000003287 bathing Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- PSGQCCSGKGJLRL-UHFFFAOYSA-N 4-methyl-2h-chromen-2-one Chemical compound C1=CC=CC2=C1OC(=O)C=C2C PSGQCCSGKGJLRL-UHFFFAOYSA-N 0.000 description 1
- RTORNQDWFDEDPT-UHFFFAOYSA-N 4-methyl-7-phenylmethoxychromen-2-one Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1OCC1=CC=CC=C1 RTORNQDWFDEDPT-UHFFFAOYSA-N 0.000 description 1
- GLCBOQQZRISLFQ-UHFFFAOYSA-N 4-methyl-7-prop-2-enoxychromen-2-one Chemical compound C1=C(OCC=C)C=CC2=C1OC(=O)C=C2C GLCBOQQZRISLFQ-UHFFFAOYSA-N 0.000 description 1
- UDFPKNSWSYBIHO-UHFFFAOYSA-N 7-methoxy-4-methyl-1-benzopyran-2-one Chemical compound CC1=CC(=O)OC2=CC(OC)=CC=C21 UDFPKNSWSYBIHO-UHFFFAOYSA-N 0.000 description 1
- KWNHWLBNDYLDEC-UHFFFAOYSA-N 7-prop-2-enoxychromen-2-one Chemical compound C1=CC(=O)OC2=CC(OCC=C)=CC=C21 KWNHWLBNDYLDEC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PLXMOAALOJOTIY-FPTXNFDTSA-N Aesculin Natural products OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@H]1Oc2cc3C=CC(=O)Oc3cc2O PLXMOAALOJOTIY-FPTXNFDTSA-N 0.000 description 1
- RSDDHGSKLOSQFK-PTNGSMBKSA-N Auraptene Natural products C1=CC(=O)OC2=CC(OC\C=C(C)/CCC=C(C)C)=CC=C21 RSDDHGSKLOSQFK-PTNGSMBKSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- WNBCMONIPIJTSB-BGNCJLHMSA-N Cichoriin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1)c1c(O)cc2c(OC(=O)C=C2)c1 WNBCMONIPIJTSB-BGNCJLHMSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- GNMUGVNEWCZUAA-WOWYBKFKSA-N Umbelliprenin Chemical compound C1=CC(=O)OC2=CC(OC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=CC=C21 GNMUGVNEWCZUAA-WOWYBKFKSA-N 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- RSDDHGSKLOSQFK-RVDMUPIBSA-N auraptene Chemical compound C1=CC(=O)OC2=CC(OC/C=C(C)/CCC=C(C)C)=CC=C21 RSDDHGSKLOSQFK-RVDMUPIBSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- XHCADAYNFIFUHF-TVKJYDDYSA-N esculin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)O)=CC2=C1OC(=O)C=C2 XHCADAYNFIFUHF-TVKJYDDYSA-N 0.000 description 1
- 229940093496 esculin Drugs 0.000 description 1
- AWRMZKLXZLNBBK-UHFFFAOYSA-N esculin Natural products OC1OC(COc2cc3C=CC(=O)Oc3cc2O)C(O)C(O)C1O AWRMZKLXZLNBBK-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940100242 glycol stearate Drugs 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 229910052740 iodine Chemical group 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000037307 sensitive skin Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- VPQAIISANYIHKZ-UHFFFAOYSA-N umbelliprenine Natural products CC(=CCCC=CCCC(=CCOc1ccc2C=CC(=O)Oc2c1)C)C VPQAIISANYIHKZ-UHFFFAOYSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
Definitions
- Brooks & Fitzpatrick ABSTRACT The use as sun-screening agents of essentially colorless, stable, odorless, nonirritating, nonsensitizing, and oil-compatible coumarin ether compounds, such compounds wherein R is alkenyl, cycloalkenyl, alkadienyl, cycloalkadienyl, alkatrienyl, alkoxyalkadienyl, acyloxyalkadienyl, alkoxyalkenyl, cyclialkoxyalkenyl, aryl, alkaryl, or aralkyl and R is hydrogen or lower alkyl and such compounds having ultraviolet absorption maxima within the range of 2,900 A. up to about 3,400 A.
- the compounds wherein R is lower alkyl and R is alkadienyl or where R is cycloalkadienyl or cycloalkenyl are novel compounds.
- the invention relates to composition containing specific sun-screen compounds; to methods for protecting the human skin against the burning, tanning and degradation effects of sunlight, to certain new and useful sun-screen compounds, and in particular to cosmetic compositions incorporating the compounds including the novel compounds of this invention which are outstandingly useful for protecting the skin against sunlight.
- Sun-screening compounds in general have been developed which afford satisfactory protection against the burning rays of the sun but which would permit the tanning rays to be transmitted. In the approximate range of from about 2,900 to 3,100 Angstrom Units are found the most detrimental burning wavelengths in the sun's rays. The effect of these wavelengths on the human skin is to produce a severe burning, reddening, blistering and edema which is characteristic of many burns. Obviously, this is not only not desirable from an esthetic point of view, but is a severe detriment to human health. In order, therefore, to overcome this effect of the burning rays of the sun, chemical compounds have been heretofore employed to screen out these burning rays.
- tanning is a desirable phenomenon and is somewhat related to good health
- the ublic has been educated to accepted the numerous products currently available to screen out the burning rays of the sun but to permit tanning to occur.
- tanning may have some beneficial effects especially in that it protects the skin from further burning where there is continued exposure to the sun, nevertheless, tanning in and of itself is associated with a general deterioration of the skin due to the effect of the actinic radiation thereon.
- the great majority of people are not severely affected by tanning, there are a great number who are so sensitive to even the tanning rays of the sun that exposure to these wavelengths creates serious health hazards.
- tanning is beautifying and would prefer to remain untanned. Consequently for those who must have protection against both burning and tanning rays of the sun, and for those who do not desire to be tanned, there has been a need for broad spectrum sun-screening compositions, which would give adequate protection to the skin, would be sufficiently stable under conditions of use to remain effective for several hours, which could be readily applied to the skin, which would be compatible with the various oily cosmetic compositions currently on the market, which would be aesthetically pleasing (for example, odorless) which would be nonirritating and nonsensitizing to the skin and which would not be readily removed such as by simple water-wash.
- the need for the latter characteristic is evident since it would leave one with a false sense of security if the material were readily removed as, for example, in bathing.
- nonsensitizing is used herein to mean that the compounds of this invention will not induce or enhance or augment photosensitivity of the skin on exposure to ultraviolet light for a wavelength in the range of from about 2900 A. to about 3400 a.
- compositions which has an outstanding filtering action on those rays of the sun from about 2900 A. to about 3400 A.; which range encompasses the burning and tanning wavelengths present in sunlight, and (2) which is odorless, nonirritating and nonsensitizing to the skin.
- compositions having the foregoing properties which is either substantially oil-miscible or capable of forming a nongranular smooth suspension in oils [such as those used in standard cosmetic sun-screen compositions for application to the skin] so as to be compatible with the various cosmetic compositions currently available to the public.
- One of the objects, therefore, of the present invention is to provide outstanding and useful compounds and compositions containing same which have excellent filtering action on the ultraviolet rays of solar light and particularly those wavelengths of from about 2,900 A. to about 3,400 A., as well as the ability to absorb the said rays even if the pH of the environment of the compound varies moderately.
- a class of compounds hereinafter to be described has outstanding screening characteristics for the burning and tanning rays of the sun, and particularly those wavelengths in the ultraviolet region of from about 2,900 A. to about 3,400 A.; (2) that such compounds have unexpected superior light fastness and stability upon exposure to ultraviolet radiation; (3) that such compounds maintain their screening characteristics notwithstanding a change in the pH of the environment of said compounds; 4) that such compounds are compatible (that is, form stable suspensions or are miscible) with oily compositions suitable for application to the human skin; and (5) that such compounds are odorless, nonirritating and nonsensitizing to human skin.
- compositions containing 4-methyl-7- methoxy coumarin or other 4-methyl-7-lower alkoxy coumarin or esculin (6,7dihydroxy coumarin-o-glucoside) have not been found to have all of the advantageous properties of the compounds of this invention; particularly with regard to compatibility with oily compositions, and consistency of sunscreening characteristics (in the event of a change in the pH of the environment of the compound).
- R is alkenyl, cycloalkenyl, alkadienyl, cycloalkadienyl, alkatrienyl, alkoxyalkadienyl, acyloxyalkadienyl, alkoxyalkenyl, cyclialkoxyalkenyl, aryl, alkaryl or aralkyl and R is hydrogen or lower alkyl.
- Suitable R groups are:
- alkoxyalkadienyl of eight to 30 carbon atoms 10. acyloxyalkadienyl of eight to 30 carbon atoms; l l. alkoxyalkenyl of eight to 30 carbon atoms; 12. cyclialkoxyalkenyl of eight to 30 carbon atoms.
- Suitable R groups are:
- R classes (2) and (4) and compounds of class (3) wherein R is lower alkyl are novel compounds.
- the novel methyl-substituted compounds of class (3) are surprisingly oil soluble.
- the general procedure for preparing the compounds found to be useful in this invention involves the reaction of a suitable halide with either 7-hydroxy coumarin (umbelliferone) or 7- hydroxy-4-lower alkyl coumarin.
- Suitable halide reactants are: alkenyl chlorides or bromides having three to 15 carbon atoms;
- alkaryl chlorides and bromides having from seven to 30 carbon atoms
- aryl chlorides, bromides and iodides having from six to 14 carbon atoms;
- alkoxyalkadienyl chlorides of eight to 30 carbon atoms
- alkoxyalkenyl chlorides of eight to 30 carbon atoms
- the condensation is carried out in the presence of a base, such as an alkali metal carbonate or bicarbonate, for example, potassium carbonate or sodium carbonate and in an organic solvent compatible with the reactants preferably an alkyl or alicylic ketone such as acetone or cyclohexanone.
- a base such as an alkali metal carbonate or bicarbonate, for example, potassium carbonate or sodium carbonate
- organic solvent compatible with the reactants preferably an alkyl or alicylic ketone such as acetone or cyclohexanone.
- a catalyst such as potassium or sodium iodide in order to speed the reaction.
- the period of reaction varies from about 10 hours up to about 30 hours depending upon the particular halide used as the reactant and the yield of product desired.
- the reaction product is isolated in the usual manner by means of crystallization or distillation where feasible.
- R classes 8,9,l0,10,l l, and 12 may also be produced using the procedures set forth in Caglioti et al., Helvetica Chim. Acta, Volume XLIl, Fasciculus Vll, 1959, No. 273-4, pages 2557-2564.
- Suitable ethers useful in this invention are:
- Umbelliprenine having the structure:
- oil sun-screening compositions The range of usage of these compounds which are novel which have been herein shown to be useful in oil sun-screening compositions is from about 1 percent up to about 10 percent (based on the weight of the final formula which is ready for use) with the preferred range being from about 1 up to about 6 by weight
- Any oily carrier suitable for application to the human skin may be used, for example, lanolin, cetyl alcohol, wheat germ oil, sesame oil, polyethylene glycol stearate (wherein the polyethylene glycol moiety has a molecular weight of less than 400), other fatty acid esters of polyethylene glycol (wherein the polyethylene glycol moiety has a molecular weight of less than 400) and the like.
- application to the human skin may be made in any convenient and comfortable manner.
- An expedient application quantity is in the range of from 5 up to about 200 milligrams (of active ultraviolet absorption compound (coumarin ether)) per square meter of skin, depending upon the environment of exposure and the nature of the skin being exposed. Thus, for example, exposure to high intensity ultraviolet radiation of highly sensitive skin would necessitate application concentrations at the upper part of the foregoing range.
- the compounds of example [ll-V were each added to a separate sample of the cream set forth in example ll. Substantially identical results were obtained using the compounds of examples lll-V, in place ofthe compound ofexample l, except that the compounds of examples Ill-V apparently formed suspensions rather than miscible systems with the oily sunscreen materials. Nevertheless, the products of examples lll-V were found to be compatible with the oily carrier.
- R is selected from the group consisting of alkenyl of three to carbon atoms, cycloalkenyl of five to eight carbon atoms, alkadienyl of five to carbon atoms, cycloalkadienyl of six to 10 carbon atoms, carbocyclic aryl of six to 14 carbon atoms, alkatrienyl of eight to [5 carbon atoms, alkoxyalkadienyl of eight to 30 carbon atoms, lower alkanoyloxyalkadienyl of eight to 30 carbon atoms, alkoxyalkenyl of eight to 30 carbon atoms and cyclialkoxyalkenyl of eight to 30 carbon'atoms and R, is selected from the group consisting of hydrogen and lower alkyl, comprising the steps of intimately admixing in the presence of potassium or sodium iodide, the 'compouncLR x and a compound having the structure:
- R is hydrogen or lower alkyl, R, is as defined as above, and X is selected from the group consisting of chlorine, bromine and iodine.
Abstract
WHEREIN R1 is alkenyl, cycloalkenyl, alkadienyl, cycloalkadienyl, alkatrienyl, alkoxyalkadienyl, acyloxyalkadienyl, alkoxyalkenyl, cyclialkoxyalkenyl, aryl, alkaryl, or aralkyl and R2 is hydrogen or lower alkyl and such compounds having ultraviolet absorption maxima within the range of 2,900 A. up to about 3,400 A. The compounds wherein R2 is lower alkyl and R1 is alkadienyl or where R1 is cycloalkadienyl or cycloalkenyl are novel compounds.
The use as sun-screening agents of essentially colorless, stable, odorless, nonirritating, nonsensitizing, and oilcompatible coumarin ether compounds, such compounds having the formula:
The use as sun-screening agents of essentially colorless, stable, odorless, nonirritating, nonsensitizing, and oilcompatible coumarin ether compounds, such compounds having the formula:
Description
Unite States Patent [72] Inventor Ernst Theodore Thelmer Rumson, NJ.
[21 Appl. No. 883,239
[22] Filed Dec. 9, 1969 [45] Patented Dec. 7, 1971 [73] Assignee International Flavors & Fragrances, Inc.
New York, N.Y.
[54] COUMARIN ETHER SUN-SCREENING COMPOUNDS 3 Claims, No Drawings [52] U.S. Cl 260/343.2R,
424/59, 252/300 [51] Int. Cl C07d 7/26 [50] Field of Search 260/343.2R
[56] References Cited UNITED STATES PATENTS 3,282,938 l H1966 Ritter et al 260/3432 X 3,35l,482 ll/l967 Raue 260/343.2X
Primary ExaminerJohn M. Ford Attorneys-Arthur L. Liberman and Ward, McElhannon,
Brooks & Fitzpatrick ABSTRACT: The use as sun-screening agents of essentially colorless, stable, odorless, nonirritating, nonsensitizing, and oil-compatible coumarin ether compounds, such compounds wherein R is alkenyl, cycloalkenyl, alkadienyl, cycloalkadienyl, alkatrienyl, alkoxyalkadienyl, acyloxyalkadienyl, alkoxyalkenyl, cyclialkoxyalkenyl, aryl, alkaryl, or aralkyl and R is hydrogen or lower alkyl and such compounds having ultraviolet absorption maxima within the range of 2,900 A. up to about 3,400 A. The compounds wherein R is lower alkyl and R is alkadienyl or where R is cycloalkadienyl or cycloalkenyl are novel compounds.
COUMARIN ETHER SUN-SCREENING COMPOUNDS THE INVENTION The invention relates to composition containing specific sun-screen compounds; to methods for protecting the human skin against the burning, tanning and degradation effects of sunlight, to certain new and useful sun-screen compounds, and in particular to cosmetic compositions incorporating the compounds including the novel compounds of this invention which are outstandingly useful for protecting the skin against sunlight.
No one material possessing all of the desirable characteristics of sun-screening compounds including (l) stability; (2) lack of odor; (3) no causation of irritation to the skin; (4) no causation of sensitization of the human skin on exposure to sunlight; (5) oil compatibility; (6) protection against both the burning rays and the tanning rays of the sun; have heretofore been described.
Sun-screening compounds in general have been developed which afford satisfactory protection against the burning rays of the sun but which would permit the tanning rays to be transmitted. In the approximate range of from about 2,900 to 3,100 Angstrom Units are found the most detrimental burning wavelengths in the sun's rays. The effect of these wavelengths on the human skin is to produce a severe burning, reddening, blistering and edema which is characteristic of many burns. Obviously, this is not only not desirable from an esthetic point of view, but is a severe detriment to human health. In order, therefore, to overcome this effect of the burning rays of the sun, chemical compounds have been heretofore employed to screen out these burning rays. On the assumption and general acceptance by the public that tanning is a desirable phenomenon and is somewhat related to good health," the ublic has been educated to accepted the numerous products currently available to screen out the burning rays of the sun but to permit tanning to occur. Within the recent years it has become generally accepted that while tanning may have some beneficial effects especially in that it protects the skin from further burning where there is continued exposure to the sun, nevertheless, tanning in and of itself is associated with a general deterioration of the skin due to the effect of the actinic radiation thereon. While the great majority of people are not severely affected by tanning, there are a great number who are so sensitive to even the tanning rays of the sun that exposure to these wavelengths creates serious health hazards. Others have not quite accepted the notion that tanning is beautifying and would prefer to remain untanned. Consequently for those who must have protection against both burning and tanning rays of the sun, and for those who do not desire to be tanned, there has been a need for broad spectrum sun-screening compositions, which would give adequate protection to the skin, would be sufficiently stable under conditions of use to remain effective for several hours, which could be readily applied to the skin, which would be compatible with the various oily cosmetic compositions currently on the market, which would be aesthetically pleasing (for example, odorless) which would be nonirritating and nonsensitizing to the skin and which would not be readily removed such as by simple water-wash. The need for the latter characteristic is evident since it would leave one with a false sense of security if the material were readily removed as, for example, in bathing.
The term "nonsensitizing" is used herein to mean that the compounds of this invention will not induce or enhance or augment photosensitivity of the skin on exposure to ultraviolet light for a wavelength in the range of from about 2900 A. to about 3400 a.
In order, therefore, to achieve the ends of the present invention, it is necessary to provide a composition (1 which has an outstanding filtering action on those rays of the sun from about 2900 A. to about 3400 A.; which range encompasses the burning and tanning wavelengths present in sunlight, and (2) which is odorless, nonirritating and nonsensitizing to the skin.
it is further necessary to provide a composition having the foregoing properties which is either substantially oil-miscible or capable of forming a nongranular smooth suspension in oils [such as those used in standard cosmetic sun-screen compositions for application to the skin] so as to be compatible with the various cosmetic compositions currently available to the public.
It is further necessary to provide a composition having the foregoing properties, the ultraviolet radiation absorption properties of which will not be transformed as a result of a change in the pH of the environment of the compound.
One of the objects, therefore, of the present invention is to provide outstanding and useful compounds and compositions containing same which have excellent filtering action on the ultraviolet rays of solar light and particularly those wavelengths of from about 2,900 A. to about 3,400 A., as well as the ability to absorb the said rays even if the pH of the environment of the compound varies moderately.
it is still another object of the present invention to provide oily compositions, and particularly cosmetic compositions,
which may be applied to the human skin to protect it against T1 the burning and tanning rays of the sun and which are odorless, nonirritating and nonsensitizing to the skin;
It is a still further object of the present invention to provide processes for preparing certain of the compounds with which the present invention is concerned and further, to provide processes for protecting the human skin against the burning and tanning rays of the sun.
Other objects will appear hereinafter as the description proceeds.
in accordance with the objects of the present invention, it has now been discovered that (l) a class of compounds hereinafter to be described has outstanding screening characteristics for the burning and tanning rays of the sun, and particularly those wavelengths in the ultraviolet region of from about 2,900 A. to about 3,400 A.; (2) that such compounds have unexpected superior light fastness and stability upon exposure to ultraviolet radiation; (3) that such compounds maintain their screening characteristics notwithstanding a change in the pH of the environment of said compounds; 4) that such compounds are compatible (that is, form stable suspensions or are miscible) with oily compositions suitable for application to the human skin; and (5) that such compounds are odorless, nonirritating and nonsensitizing to human skin.
Known compositions containing 4-methyl-7-hydroxycoumarin [See British Pat. 464,732 and Gregoire et al. Ann. Pharm. Franc, 9, 493-513 (ll] have not been found to have all of the foregoing advantages. Such compounds do not have such stability that their screening characteristics are maintained in the event of a change in the pH of the environment of the compound; nor are they considered to be compatible with oily compositions suitable for application to the human skin, as are the compounds of this invention. By the same token, known compositions containing 4-methyl-7- methoxy coumarin or other 4-methyl-7-lower alkoxy coumarin or esculin (6,7dihydroxy coumarin-o-glucoside) have not been found to have all of the advantageous properties of the compounds of this invention; particularly with regard to compatibility with oily compositions, and consistency of sunscreening characteristics (in the event of a change in the pH of the environment of the compound).
The compounds found to be useful in the present invention and those which are employed in the compositions and processes of this invention have the following general formulas:
wherein R is alkenyl, cycloalkenyl, alkadienyl, cycloalkadienyl, alkatrienyl, alkoxyalkadienyl, acyloxyalkadienyl, alkoxyalkenyl, cyclialkoxyalkenyl, aryl, alkaryl or aralkyl and R is hydrogen or lower alkyl.
Suitable R groups are:
. alkenyl of three to 15 carbon atoms;
. cycloalkenyl of five to eight carbon atoms;
. alkadienyl of five to 20 carbon atoms;
. cycloalkadienyl of six to carbon atoms;
. aralkyl of seven to 30 carbon atoms;
. alkaryl of seven to 30 carbon atoms;
aryl ofsix to 14 carbon atoms;
. alkatrienyl of eight to carbon atoms;
alkoxyalkadienyl of eight to 30 carbon atoms; 10. acyloxyalkadienyl of eight to 30 carbon atoms; l l. alkoxyalkenyl of eight to 30 carbon atoms; 12. cyclialkoxyalkenyl of eight to 30 carbon atoms. Suitable R groups are:
. hydrogen;
methyl;
ethyl;
. n-propyl;
. i-propyl;
n-butyl;
Compounds of R classes (2) and (4) and compounds of class (3) wherein R is lower alkyl are novel compounds. The novel methyl-substituted compounds of class (3) are surprisingly oil soluble.
The general procedure for preparing the compounds found to be useful in this invention involves the reaction of a suitable halide with either 7-hydroxy coumarin (umbelliferone) or 7- hydroxy-4-lower alkyl coumarin. Suitable halide reactants are: alkenyl chlorides or bromides having three to 15 carbon atoms;
2. cycloalkenyl chlorides or bromides having three to 15 carbon atoms;
3. alkadienyl chlorides or bromides having from five to carbon atoms;
4. cycloalkadienyl chlorides or bromides having from six to 10 carbon atoms;
5. aralkyl chlorides or bromides having from seven to carbon atoms;
6. alkaryl chlorides and bromides having from seven to 30 carbon atoms;
7. aryl chlorides, bromides and iodides having from six to 14 carbon atoms;
8. alkatrienyl chlorides of eight to 15 carbon atoms;
9. alkoxyalkadienyl chlorides of eight to 30 carbon atoms;
10. acyloxyalkadienyl chlorides of eight to 30 carbon atoms;
1 l. alkoxyalkenyl chlorides of eight to 30 carbon atoms;
l2. cyclialkoxyalkenyl cuclialkoxyalkenyl chlorides of eight of 30 carbon atoms;
The condensation is carried out in the presence of a base, such as an alkali metal carbonate or bicarbonate, for example, potassium carbonate or sodium carbonate and in an organic solvent compatible with the reactants preferably an alkyl or alicylic ketone such as acetone or cyclohexanone. Most preferably in view of convenience and economy the reaction is carried out at atmospheric pressure and at reflux conditions. Higher temperatures of reaction, and consequently higher pressures, will reduce the time of reaction. It is desirable, to add a catalyst such as potassium or sodium iodide in order to speed the reaction. At higher temperatures, the period of reaction varies from about 10 hours up to about 30 hours depending upon the particular halide used as the reactant and the yield of product desired. At the end of the period of reaction, the reaction product is isolated in the usual manner by means of crystallization or distillation where feasible.
Compounds of R classes 8,9,l0,10,l l, and 12 may also be produced using the procedures set forth in Caglioti et al., Helvetica Chim. Acta, Volume XLIl, Fasciculus Vll, 1959, No. 273-4, pages 2557-2564.
Among suitable ethers useful in this invention are:
7-allyloxy-4-methyl coumarin; 7( 3-methyl-2-butenl -oxy)-4-methyl coumarin; 7-neryloxy-4-t-butyl coumarin; 7-geranyloxy-4-n-propyl coumarin; 7-geranyloxy-4( l-n-butyl) coumarin; 7-benzoxy-4-methyl coumarin; 7-benzoxy-4-ethyl coumarin; 7-allyloxy coumarin; 7-(3-methyl cyclo hex-2-en) oxy-4-methyl coumarin; 7-geranyloxy 4-methyl coumarin; 7-neryloxy-4-methyl coumarin; 7( 3-methyl-2butenl -oxy) coumarin; 7( 3-methyl-2-butenl -oxy )-4-n-propyl coumarin; 7-benzoxy coumarin; 7(6-ethyl-cycloocta-2,4dien) oxy-4-methyl coumarin; A mixture of 7-geranyloxy and 7-neryloxy coumarin; A mixture of 7-geranyloxy and 7-neryloxy-4-methyl coumarins. The compound of the structure:
r, I i
Umbelliprenine having the structure:
The range of usage of these compounds which are novel which have been herein shown to be useful in oil sun-screening compositions is from about 1 percent up to about 10 percent (based on the weight of the final formula which is ready for use) with the preferred range being from about 1 up to about 6 by weight Any oily carrier suitable for application to the human skin may be used, for example, lanolin, cetyl alcohol, wheat germ oil, sesame oil, polyethylene glycol stearate (wherein the polyethylene glycol moiety has a molecular weight of less than 400), other fatty acid esters of polyethylene glycol (wherein the polyethylene glycol moiety has a molecular weight of less than 400) and the like. After producing the formulation, application to the human skin may be made in any convenient and comfortable manner. An expedient application quantity is in the range of from 5 up to about 200 milligrams (of active ultraviolet absorption compound (coumarin ether)) per square meter of skin, depending upon the environment of exposure and the nature of the skin being exposed. Thus, for example, exposure to high intensity ultraviolet radiation of highly sensitive skin would necessitate application concentrations at the upper part of the foregoing range.
The following examples serve only to illustrate the present invention. Percentages by weight are set forth therein unless otherwise indicated.
EXAMPLE I PREPARATION OF A MIXTURE OF 7-GERANYLOXY-4- METHYL COUMARIN AND 7-NERYLOXY-4-METHYL COUMARIN To a flask fitted with a stirrer, a condenser and a thermometer was added 200 g. 1.14 moles) 4-methyl umbelliferone 280 g. 1.2 moles 77 percent) cold myrcene hydrochloride. consisting predominantly of geranyl and neryl chlorides produced by the process of U.S. Pat. No. 2,882,323,680 g. of potassium carbonate, 10 g. of potassium iodide and 3.5 liters of acetone. The mixture was stirred and refluxed for hours. The solution was filtered, and the supernatant liquid was retained for subsequent workup. Solid residue from this filtration was dissolved in a 2N NaOH solution and this solution was then extracted with 3 500 ml. volumes of CHgClz- The organic phases (the aforesaid supernatant liquid and the CH,CI extracts) were combined and washed with 2 equal volumes of 2N sodium hydroxide solution, followed by two equal volumes of 20 water. 310 g. of crude reaction material was thereby produced. This crude product was steam distilled, to give 55 g. of steam volatiles. The residue after steam distillation was taken up in methylene chloride, and separated from the water layer. The organic layer was subjected to crystallization from petroleum ether to give 225 g. of a mixture of cis and trans isomers, 7-geranyloxy-4-methyl coumarin and 7-neryloxyl-4- methyl coumarin. The following structures were confirmed by NMR data:
(7-neryloxy coumarin) (7geranyloxy coumarin) s at 3220 A.=18100 (Extinction Coeflicient) NMR data: p.p.m. 1.58, 1.63 (singlet, 3H each) 1.74 (doublet 3H,
set-@l) (singlet, 3H,
6.08 (singlet, 1H,
6.85 (2H, two aromatic protons), 7.54 (doublet, 1H, a om ti J EXAMPLE ll The product of example I was incorporated into a neutral sun-screen cream as follows:
The unexpected high miscibility of the product of example I made it possible to fon'nulate the above homogeneous cream. This cream was then used separately by five people in a bathing procedure, and thereafter the live persons were exposed to the summer afternoon sun for 2 hours. A similar group of five persons used a similar cream but devoid of the product of example I, and these individuals were exposed similarly to the first group. All of the persons in the second group, after exposure, showed considerable reddening of the skin whereas none of the persons in the first group had any visible evidence of sunburn. This demonstrates the sun- 'screening properties of the compound of example I.
Examples Ill-V in the following examples, example I was carried out except that in place of myrcene hydrochloride, there were used the Examples Vl-Vlll The compounds of example [ll-V were each added to a separate sample of the cream set forth in example ll. Substantially identical results were obtained using the compounds of examples lll-V, in place ofthe compound ofexample l, except that the compounds of examples Ill-V apparently formed suspensions rather than miscible systems with the oily sunscreen materials. Nevertheless, the products of examples lll-V were found to be compatible with the oily carrier.
What is claimed is:
l. A compound ofthe formula:
wherein R is selected from the group consisting of alkenyl of three to carbon atoms, cycloalkenyl of five to eight carbon atoms, alkadienyl of five to carbon atoms, cycloalkadienyl of six to 10 carbon atoms, carbocyclic aryl of six to 14 carbon atoms, alkatrienyl of eight to [5 carbon atoms, alkoxyalkadienyl of eight to 30 carbon atoms, lower alkanoyloxyalkadienyl of eight to 30 carbon atoms, alkoxyalkenyl of eight to 30 carbon atoms and cyclialkoxyalkenyl of eight to 30 carbon'atoms and R, is selected from the group consisting of hydrogen and lower alkyl, comprising the steps of intimately admixing in the presence of potassium or sodium iodide, the 'compouncLR x and a compound having the structure:
wherein R is hydrogen or lower alkyl, R, is as defined as above, and X is selected from the group consisting of chlorine, bromine and iodine.
' I v i Page 2 UNITED STATES PATENT 3 0F vCQRYECTION Patent No. 3,625,97 Dated- December 7, Q1971 lnv ntefle) ERNST THEODORE TEEIMER' It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Col-.1, line 28 underline "not" second occurrence Col. 1, line 35 change "accepted" to --accept -5 Col. 3, line 53 Col. 3, lineBM change "of" to --to-; Col. 3, lines 58/59- change "alicylic" to --alicyclic---;"
Col. 3, line 71 eshould read: --Compounds of R classes 8, 9, 10, 11 and 12, may also be-;
Col. L, line 13 insert -a hyphen-e after "2;
Col. L,line 5O insert or---- before "which" at the beginning of the line;
L, line 50 change "011 to -oily-3 Col. LL, line 53 insert -percent after "1"; 7
L, line 5 L insert -percentafter "6";
Col. L, line 5M insert a -period after "weight";
Col. 5, line 17 change '3 500 ml." to three 500 mi.--; Col. 5, line #5 underline "CH both occurrences;
v Pae Of 2 UNITED STATES PATENT OFFICE x CERTIFICATE OF CORRECTION Patent No. 3,625,976 Dated December 7, 1971 Inventor(s) ERNST THEODORE THEIMER It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Col. 5, line #6 insert a comma-- after "3";
5, line 5 I underline "H Col; 5, line 51 underline H; both occurrences;
Col. 5, line 55 underline "H second occurrence;
Col. 5, line 75 should read:
I CH3 ,--5. L1 (broad, C=CHCH -s I 1/ 2 6, line 1 underline "H second occurrence;
(fol. 6, line 5 underline "H" first occurrence;
CO1, .6, lines 24/25 put in parentheses "A mixture of methyl and n-propyl parahydroxy benzoate-s in a weight ratio ofv 1:5";
Col. 6, Examples III-V, last Column in the Table should read: Ultraviolet Data at 3220A)".
Signed and sealed this J tll day of July 1972.
(SEAL) Attest:
EDWARD MELETGdHR; JE- ROBERT GOTTSGlIAL-ll Attestirig Officer Commissioner of Patents
Claims (2)
- 2. A mixture of 7-geranoxy-4-methyl coumarin and 7-neryloxy-4-methyl coumarin.
- 3. A process for preparing a compound having the formula:
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US883239A US3625976A (en) | 1969-12-09 | 1969-12-09 | Coumarin ether sun-screening compounds |
US00165343A US3712947A (en) | 1969-12-09 | 1971-07-22 | Compositions containing coumarin ether sun-screening compounds |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US883239A US3625976A (en) | 1969-12-09 | 1969-12-09 | Coumarin ether sun-screening compounds |
Publications (1)
Publication Number | Publication Date |
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US3625976A true US3625976A (en) | 1971-12-07 |
Family
ID=25382248
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---|---|---|---|
US883239A Expired - Lifetime US3625976A (en) | 1969-12-09 | 1969-12-09 | Coumarin ether sun-screening compounds |
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US5034213A (en) * | 1986-09-22 | 1991-07-23 | L'oreal | Photostable cosmetic composition containing an ethylrutin derivative as protective agent against sunlight and its use in the protection of the skin and the hair |
US5100914A (en) * | 1988-10-13 | 1992-03-31 | Basf Aktiengesellschaft | Arylalkoxycoumarins |
US6051602A (en) * | 1998-03-16 | 2000-04-18 | The Procter & Gamble Company | Methods for regulating skin appearance |
US6555143B2 (en) | 2001-02-28 | 2003-04-29 | Johnson & Johnson Consumer Products, Inc. | Legume products |
US6750229B2 (en) | 1998-07-06 | 2004-06-15 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin pigmentation |
US7192615B2 (en) | 2001-02-28 | 2007-03-20 | J&J Consumer Companies, Inc. | Compositions containing legume products |
US7309688B2 (en) | 2000-10-27 | 2007-12-18 | Johnson & Johnson Consumer Companies | Topical anti-cancer compositions and methods of use thereof |
US20100227039A1 (en) * | 2009-03-03 | 2010-09-09 | Givaudan S.A. | Off-Taste Masking |
US7985404B1 (en) | 1999-07-27 | 2011-07-26 | Johnson & Johnson Consumer Companies, Inc. | Reducing hair growth, hair follicle and hair shaft size and hair pigmentation |
US8039026B1 (en) | 1997-07-28 | 2011-10-18 | Johnson & Johnson Consumer Companies, Inc | Methods for treating skin pigmentation |
US8093293B2 (en) | 1998-07-06 | 2012-01-10 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin conditions |
US8106094B2 (en) | 1998-07-06 | 2012-01-31 | Johnson & Johnson Consumer Companies, Inc. | Compositions and methods for treating skin conditions |
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FR2395025A1 (en) * | 1977-06-23 | 1979-01-19 | Henkel Kgaa | COSMETIC PRODUCTS INTENDED TO PROTECT AGAINST LIGHT, IN PARTICULAR THE LIGHT OF THE REGION WITH THE ULTRAVIOLET SPECTRUM |
US5034213A (en) * | 1986-09-22 | 1991-07-23 | L'oreal | Photostable cosmetic composition containing an ethylrutin derivative as protective agent against sunlight and its use in the protection of the skin and the hair |
US5100914A (en) * | 1988-10-13 | 1992-03-31 | Basf Aktiengesellschaft | Arylalkoxycoumarins |
US8039026B1 (en) | 1997-07-28 | 2011-10-18 | Johnson & Johnson Consumer Companies, Inc | Methods for treating skin pigmentation |
US6051602A (en) * | 1998-03-16 | 2000-04-18 | The Procter & Gamble Company | Methods for regulating skin appearance |
US6093411A (en) * | 1998-03-16 | 2000-07-25 | The Procter & Gamble Company | Compositions for regulating skin appearance |
US6235773B1 (en) | 1998-03-16 | 2001-05-22 | The Procter & Gamble Company | Compositions for regulating skin appearance |
US8093293B2 (en) | 1998-07-06 | 2012-01-10 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin conditions |
US8106094B2 (en) | 1998-07-06 | 2012-01-31 | Johnson & Johnson Consumer Companies, Inc. | Compositions and methods for treating skin conditions |
US6750229B2 (en) | 1998-07-06 | 2004-06-15 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin pigmentation |
US7985404B1 (en) | 1999-07-27 | 2011-07-26 | Johnson & Johnson Consumer Companies, Inc. | Reducing hair growth, hair follicle and hair shaft size and hair pigmentation |
US7879823B2 (en) | 1999-11-05 | 2011-02-01 | Johnson & Johnson Consumer Companies | Topical anti-cancer compositions and methods of use thereof |
US7309688B2 (en) | 2000-10-27 | 2007-12-18 | Johnson & Johnson Consumer Companies | Topical anti-cancer compositions and methods of use thereof |
US8431550B2 (en) | 2000-10-27 | 2013-04-30 | Johnson & Johnson Consumer Companies, Inc. | Topical anti-cancer compositions and methods of use thereof |
US7897144B2 (en) | 2001-02-28 | 2011-03-01 | Johnson & Johnson Comsumer Companies, Inc. | Compositions containing legume products |
US7192615B2 (en) | 2001-02-28 | 2007-03-20 | J&J Consumer Companies, Inc. | Compositions containing legume products |
US6555143B2 (en) | 2001-02-28 | 2003-04-29 | Johnson & Johnson Consumer Products, Inc. | Legume products |
US20100227039A1 (en) * | 2009-03-03 | 2010-09-09 | Givaudan S.A. | Off-Taste Masking |
CN102413713A (en) * | 2009-03-03 | 2012-04-11 | 奇华顿股份有限公司 | Off-taste masking |
US8329239B2 (en) * | 2009-03-03 | 2012-12-11 | Givandan S.A. | Off-taste masking |
JPWO2011108499A1 (en) * | 2010-03-03 | 2013-06-27 | 株式会社エリナ | Osteoblast differentiation-promoting agent, pharmaceutical composition for promoting bone formation, and functional food for health, containing aurapten-related compounds as active ingredients |
JP2017105798A (en) * | 2010-03-03 | 2017-06-15 | 株式会社エリナ | Osteoblast differentiation promoter comprising aurapten analog as active ingredient, pharmaceutical composition for promoting bone formation and health-promoting food |
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