A method of stimulating tear secretion and mucin production in eyes comprising the step of administering to the eyes an effective amount of a preparation which includes a compound selected from a group consisting of uridine 5′-triphosphate and derivatives as depicted in Formula I, dinucleotides as depicted in Formulae II, II(a) and II(b), adenosine 5′-triphosphate derivatives as depicted in Formula III, and cytidine 5′-triphosphate derivatives as depicted in Formula IV, and their pharmaceutically acceptable salts;
- and
- a physiologically compatible vehicle selected from the group consisting of aqueous electrolyte solutions, polyethers, polyvinyls, polymers of acrylic acid, lanolin, and glucosaminoglycans;
- whereby said preparation promotes tear secretion and mucin production in the eyes in a subject in need of such treatment:
- wherein:
- X1, X2 and X3 are each independently either O− or S−;
- R1 is O, imido, methylene or dihalomethylene;
- R2 is H or Br;
- wherein:
- X is oxygen, imido, methylene or difluoromethylene;
- n=0 or 1;
- m=0 or 1;
- n+m=0, 1 or 2;
- and
- B and B′ are each independently a purine residue, as in Formula IIa, or a pyrimidine residue, as in Formula IIb, linked through the 9- or 1-position, respectively:
- wherein:
- R3 is NHR1;
- R1 of the 6- or 8-HNR1 groups is chosen from the group consisting of hydrogen, arylalkyl (C1-6) groups;
- and alkyl groups with functional groups selected from the group consisting of ([6-aminohexyl]carbamoylmethyl)-, ω-acylated-amino(hydroxy, thiol or carboxy)alkyl(C2-10)- and ω-acylated-amino (hydroxy, thiol or carboxy) derivatives where the acyl group is chosen from the group consisting of acetyl, trifluroacetyl, benzoyl, and substituted-benzoyl;
- wherein:
- R4 is hydroxy, mercapto, amino, cyano, aralkoxy, C1-6 alkoxy, C1-6 alkylamino or dialkylamino, with the alkyl groups optionally linked to form a heterocycle;
- R5 is hydrogen, acyl, C1-6 alkyl, aroyl, C1-5 alkanoyl, benzoyl, or sulphonate;
- R6 is hydroxy, mercapto, alkoxy, aralkoxy, C1-6-alkylthio, C1-5 disubstituted amino, triazolyl, alkylamino or dialkylamino, where the alkyl groups are optionally linked to form a heterocycle or linked to N3 to form an optionally substituted ring;
- R7 is hydrogen, hydroxy, cyano, nitro, alkenyl with the alkenyl moiety optionally linked through oxygen to form a ring optionally substituted on the carbon adjacent to the oxygen with alkyl or aryl groups, substituted alkynyl, halogen, alkyl, substituted alkyl, perhalomethyl, C2-6 alkyl, C2-3 alkenyl, or substituted ethenyl, C2-3 alkynyl or substituted alkynyl;
- or together R6-R7 form a 5 or 6-membered saturated or unsaturated ring bonded through N or O at R6, such a ring optionally contains substituents that themselves contain functionalities;
- provided that when R8 is amino or substituted amino, R7 is hydrogen;
- and
- R8 is hydrogen, alkoxy, arylalkoxy, alkylthio, arylalkylthio, carboxamidomethyl, carboxymethyl, methoxy, methylthio, phenoxy or phenylthio;
- wherein:
- R1, X1, X2 and X3 are defined as in Formula I;
- R3 and R4 are H while R2 is nothing and there is a double bond between N-1 and C-6, or
- R3 and R4 are H while R2 is O and there is a double bond between N-1 and C-6, or
- R3, R4 and R2 taken together are —CH═CH—, forming a ring from N-6 to N-1 with a double bond between N-6 and C-6;
- wherein:
- R1, X1, X2 and X3 are defined as in Formula I;
- R5 and R6 are H while R7 is nothing and there is a double bond between N-3 and C-4, or
- R5, R6 and R7 taken together are —CH═CH—, forming a ring from N-3 to N-4 with a double bond between N-4 and C-4 optionally substituted at the 4- or 5-position of the etheno ring.