RU2021101682A - COMPOSITIONS AND METHODS FOR EYE TREATMENT - Google Patents

Claims (94)

1. A method for the production/release/delivery/release of mucin from the cornea and/or into the cornea, comprising the step of administering a composition containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; optionally, one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; optionally a methyl (-CH ₃ ) or methylene (=CH ₂ ) group; a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; optionally from 1 to 10 carbon atoms; optionally 6 carbon atoms; optionally an aromatic functional group, optionally a phenyl functional group; optionally 2-methyl-prop-1,3-diene; and ii) optionally, an ophthalmologically acceptable carrier. 2. The method according to claim 1, wherein the compound and/or extract having retinol-like properties and/or beneficial effects is a plant extract or source of extracts from plants of the genus Acronychia and/or Licaria. 3. The method according to claim 2, wherein the compound and/or extract having retinol-like properties and/or beneficial effects is a plant extract or source of extracts from plants of the genus Acronychia. 4. The method of claim 3, wherein the plant extract or source of extracts from plants of the genus Acronychia is selected from the group consisting of Acronychia aberrans, Acronychia acidula, Acronychia acronychioides, Acronychia acuminate, Acronychia baeuerlenii, Acronychia chooreechillum, Acronychia crassipetala, Acronychia eungellensis, Acronychia imperforate , Acronychia laevis, Acronychia laurifolia, Acronychia littoralis, Acronychia oblongifolia, Acronychia octandra, Acronychia parviflora, Acronychia pauciflora, Acronychia pedunculata, Acronychia pubescens, Acronychia spp. . 5. The method of claim 4 wherein the plant extract or source of extracts from plants of the genus Acronychia is Acronychia acidula. 6. The method of claim. 2, in which the plant extract of Acronychia and/or Licaria contains from about 1% to about 20% of the compound of formula II by weight of the extract

(II). wherein: R ₁ is selected from the group consisting of C ₁ - C ₂₀ alkyl, C ₂ - C ₂₀ alkenyl, C ₂ - C ₂₀ alkynyl and C ₃ - C ₈ cycloalkyl or aryl; R ₂ is selected from the group consisting of hydrogen, hydroxyl, C ₁ - C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ - C ₆ alkynyl, C ₃ - C ₈ cycloalkyl or aryl, - OC ₁ - C ₆ alkyl, - OC ₂ - C ₆ alkenyl, - OC ₂ - C ₆ alkynyl, - OC ₃ - C ₈ cycloalkyl or aryl, thiol, - SC ₁ - C ₆ alkyl, - SC ₂ - C ₆ alkenyl, - SC ₂ - C ₆ alkynyl, - SC ₃ - C ₈ cycloalkyl or aryl, - NR ₄ C ₁ - C ₆ alkyl, - NR ₄ C ₂ - C ₆ alkenyl, - NR ₄ C ₂ - C ₆ alkynyl and - NR ₄ C ₃ - C ₈ cycloalkyl or aryl; R ₃ is selected from - CO ₂ H, - CO ₂ R ₄ or isosteric equivalent of a carboxyl group, where R ₄ represents C ₁ - C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₃ - C ₈ cycloalkyl or aryl; and Y represents -(CH ₂ -CH ₂ )-, -(CH ═ H) - or -(C ═ C)-. 7. The method according to claim 6, wherein the plant extract of Acronychia and/or Licaria contains from about 1% to about 20% of the compound of formula II by weight of the extract

(II). wherein: R ₁ is selected from the group consisting of C ₅ - C ₁₆ alkyl, C ₅ - C ₁₆ alkenyl and C ₅ - C ₁₆ alkynyl, more preferably C ₅ - C ₁₆ alkenyl, including, for example, farnesyl; R ₂ is selected from the group consisting of hydrogen, hydroxyl, - OC ₁ - C ₆ alkyl, - OC ₂ - C ₆ alkenyl, - OC ₂ - C ₆ alkynyl, - OC ₃ - C ₈ cycloalkyl, more preferably hydrogen, hydroxyl , - OC ₁ - C ₆ alkyl, even more preferably hydrogen or - OC ₁ - C ₃ alkyl; R ₃ is selected from - CO ₂ H, - CO ₂ R ₄ where R ₄ represents C ₁ - C ₆ alkyl or the isosteric equivalent of a carboxyl group; and Y represents -(CH ₂ -CH ₂ )- or -(CH═CH)-. 8. The method of claim 7 wherein the compound of formula (II) is in the form of an acid or an alkyl ester selected from the group consisting of 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4-farnesyloxy-3-hydroxyphenyl) -propionic acid, 3-(4-farnesyloxy-3-methoxyphenyl)-propionic acid, their alkyl esters and combinations of two or more of them. 9. The method according to claim 8, wherein the compound of formula II used in the present invention is 3-(4-farnesyloxyphenyl)-propionic acid and/or its ethyl ester. 10. The method of claim 2, wherein the compound and/or extract having retinol-like properties and/or beneficial effects is a plant extract or source of extracts from plants of the genus Licaria. 11. The method of claim 10 wherein the plant extract or source of extracts from plants of the genus Licaria is selected from the group consisting of Licaria vernicosa, Licaria brittoniana, Licaria canella, Licaria cubensis, Licaria velutina and Licaria triandra and combinations of two or more of them. 12. The method of claim 11, wherein the plant extract or source of extracts from plants of the genus Licaria is Licaria vernicosa. 13. The method according to claim 1, wherein the compound and/or extract having retinol-like properties and/or beneficial effects is an extract of bacteria or a source of extracts of the genus Actinomyces. 14. The method of claim 13 wherein the compound and/or extract having retinol-like properties and/or beneficial effects is a bacterial extract or a source of Actinomyces A5640 species extracts. 15. The method according to p. 1, in which the compound and/or extract having retinol-like properties and/or beneficial effects contains a compound of formula (I):

(I) where - dotted lines show a single or double bond; optionally, one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; 16. The method of claim 15 wherein the compound of formula I is selected from (2E,4E,6E)-7-(1,1,2,2,3,3-hexamethyl-2,3-dihydro-1H-inden- 5-yl)-3-methylocta-2,4,6-trienoic acid and 4-(1-(1,1,2,2,3,3-hexamethyl-2,3-dihydro-1H-inden-5- yl)vinyl)benzoic acid and their derivatives exhibiting retinoid-like activity, and mixtures thereof. 17. A method of maintaining the concentration of MU5AC in the lacrimal fluid in the range of 8 nanograms to 15 nanograms per milligram of protein or higher, comprising the step of administering a composition containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably a methyl (-CH ₃ ) or methylene (=CH ₂ ) functional group; A represents a carbon chain, linear, circular or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; and ii) optionally, an ophthalmologically acceptable carrier. 18. A method of treating a patient with reduced or low production/release/delivery/release of mucin from the cornea and/or into the cornea, comprising the step of locally administering to the patient's eye a composition containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; preferably one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably a methyl (-CH ₃ ) or methylene (=CH ₂ ) functional group; A represents a carbon chain, linear, circular or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably 1 to 10 carbon atoms; more preferably 6 carbon atoms; preferably an aromatic functional group, preferably a phenyl functional group; preferably 2-methyl-prop-1,3-diene, ii) optionally, an ophthalmologically acceptable carrier. 19. A method for preventing or treating symptoms of dry eye syndrome, comprising the step of locally administering to a patient a composition containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; preferably one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably methyl (-CH ₃ ) or methylene (=CH ₂ ) functional group; A represents a carbon chain, linear, circular or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably 1 to 10 carbon atoms; more preferably 6 carbon atoms; preferably an aromatic functional group, preferably a phenyl functional group; preferably 2-methyl-prop-1,3-diene; ii) one or more emollients or sedatives; and iii) optionally, an ophthalmologically acceptable carrier. 20. A method for promoting healing or increasing the rate of wound healing in and/or on the surface of a patient's eye, comprising the step of administering compositions containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; preferably one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably a methyl (-CH ₃ ) or methylene (=CH ₂ ) functional group; A represents a carbon chain, linear, circular or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably 1 to 10 carbon atoms; more preferably 6 carbon atoms; preferably an aromatic functional group, preferably a phenyl functional group; preferably 2-methyl-prop-1,3-diene. ii) optionally, an ophthalmologically acceptable carrier. 21. A method for improving the antimicrobial properties of the lacrimal fluid of a patient, including the step of administering compositions containing: i) a safe and effective amount of a compound and/or extract having retinol-like properties and/or beneficial effects for use in the treatment of dry eye syndrome, selected from one or more plant extracts or sources of extracts from plants of the genera Acronychia, Licaria, Calendula and/or Trigonella ; bacterial extracts or sources of extracts of bacteria of the genus Actinomyces; and compounds of formula (I):

(I) where - dotted lines show a single or double bond; preferably one of the dotted lines represents a double bond; R ₁ represents H, a carbon chain, linear, cyclic or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; R ₂ represents a carbon chain, linear, cyclic ring or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably a methyl (-CH ₃ ) or methylene (=CH ₂ ) functional group; A represents a carbon chain, linear, circular or branched, saturated or unsaturated, containing from 1 to 20 carbon atoms; preferably 1 to 10 carbon atoms; more preferably 6 carbon atoms; preferably an aromatic functional group, preferably a phenyl functional group; preferably 2-methyl-prop-1,3-diene. ii) optionally, an ophthalmologically acceptable carrier.