1. A method for protecting a zinc surface of a metal artifact, which comprises:
passivating the surface with an acid passivating solution; or activating the surface with an acid activating solution;
applying to the surface an aqueous priming solution of an alkali metal permanganate in the presence of halide ion, said solution having a pH of about 1 to 8;
and then further applying to the surface a seal coating solution.
2. The method of claim 1 in which said seal coating solution comprises an aqueous mixture of a lithium silicate and another alkali metal silicate in a concentration to provide from 5 to 20 wt. percent of SiO2 to said sealing solution, with each of said lithium silicate and other alkali metal silicate providing at least 10 percent of the SiO2 to the sealing solution.
3. The method of claim 1 in which said acidic passivating solution is used, which solution comprises a solution of nitric acid, oxalic acid, or a combination thereof.
4. The method of claim 1 in which the pH of the priming solution is about 1.5 to 5.
5. The method of claim 1 in which said halide ion is chloride.
6. The method of claim 1 in which said alkali metal permanganate is potassium permanganate.
7. The method of claim 1 in which the passivating or activating solution, the priming solution, and the seal coating solution are all applied to the metal artifact by sequential dipping.
8. The method of claim 1 in which said halide ion is provided to the priming solution in the form of a alkali metal chloride.
9. The method of claim 1 which is performed at a solution temperature of about 50-80\xb0 F.
10. The method of claim 1 in which said priming solution is heated to a temperature of 100\xb0-180\xb0 F.
11. The method of claim 1 in which said priming solution is applied to the metal artifact by dipping the metal artifact into said solution for at least 5 seconds.
12. The method of claim 11 in which said priming solution is applied to the metal artifact by dipping for about 10 to 30 seconds.
13. The method of claim 1 in which said seal coating solution comprises an aqueous solution of lithium polysilicate, potassium silicate, and about 0.2 to 0.5 gram perliter of a molybdic acid promoter.
14. The method of claim 13 in which the metal artifact is dipped in the sealing solution for at least about one minute.
15. The method of claim 1, in which said zinc surface is previously placed on the metal artifact by thermal diffusion.
16. A method for protecting a zinc surface of a metal artifact, which comprises:
passivating the surface with a solution comprising an oxidizing acid, or activating the surface with an acid activating solution;
applying to the surface an aqueous priming solution of an alkali metal permanganate and an alkali metal halide, said solution having a pH of about 1 to 6;
and then further applying to the surface a seal coating solution of a lithium silicate, and a sodium or potassium silicate.
17. The method of claim 16 in which a promoter is also present in said sealing solution.
18. The method of claim 16 in which the alkali metal permanganate is potassium permanganate.
19. The method of claim 16 in which the solutions are all applied to the metal artifact by sequential dipping.
20. The method of claim 16 in which said seal coating solution comprises an aqueous solution of lithium silicate and another alkali metal silicate in a concentration to provide from 5 to 20 wt. percent of SiO2 to said seal coating solution, with each of said lithium silicate and other alkali metal silicate providing at least 10 percent of the SiO2 to the sealing solution, and about 0.2 to 0.5 gram per liter of molybdic acid.
21. The method of claim 16, in which said zinc surface is previously placed on the metal artifact by thermal diffusion.
22. The method of claim 1 in which said acid passivating solution is used.
23. A metal artifact, made by the process of claim 1.
24. The method of claim 1 in which said artifact is thereafter postbaked at 250\xb0 to 400\xb0 F. to achieve a glossy coating.
25. A metal artifact, made by the process of claim 16.
26. The method of claim 16 in which said artifact is thereafter postbaked at 250\xb0 to 400\xb0 F. to achieve a glossy coating.
27. The method of claim 16 in which from 0.2 gm per liter to 120 gm of alkali metal permanganate are present.
28. The method of claim 1 in which from 0.2 gm per liter to 120 gm of alkali metal permanganate are present.
29. A metal artifact having a zinc surface coated with a coating made by the process of claim 21.
30. A metal artifact having a zinc surface coated with a coating made by the process of claim 15.
31. The method of claim 1 which is substantially free from the presence of a rare earth compound.
32. The method of claim 16 which is substantially free from the presence of a rare earth compound.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for reducing pruritus caused by multiple sclerosis, said method comprising the steps of:
identifying a patient having pruritus caused by multiple sclerosis; and
administering an effective amount of a compound represented by Formula (I) to said patient
wherein
represents a double bond or single bond;
R1 represents C1-C5 alkyl, C4-C7 cycloalkylalkyl, C5-C7 cycloalkenylalkyl, C6-C12 aryl, C7-C13 aralkyl, C4-C7 alkenyl, allyl, furan-2-ylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5) or thiophen-2-ylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5);
R2 represents hydrogen, hydroxy, nitro, C1-C5 alkanoyloxy, C1-C5 alkoxy, C1-C5 alkyl or NR9R10 wherein R9 represents hydrogen or C1-C5 alkyl and R10 represents hydrogen or C1-C5 alkyl or \u2014C(\u2550O)R11 wherein R11 represents hydrogen, phenyl or C1-C5 alkyl;
R3 represents hydrogen, hydroxy, C1-C5 alkanoyloxy or C1-C5 alkoxy;
A represents \u2014XC(\u2550Y)\u2014, \u2014XC(\u2550Y)Z\u2014, \u2014X\u2014 or \u2014XSO2\u2014 (wherein X, Y and Z independently represent NR4, S or O wherein R4 represents hydrogen, C1-C5 linear or branched alkyl or C6-C12 aryl, and wherein R4s in the formula may be the same or different);
B represents valence bond, C1-C14 linear or branched alkylene (wherein said alkylene may have at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl and phenoxy, and that 1 to 3 methylene groups therein may be replaced by a carbonyl group(s)), C2-C14 linear or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds andor triple bonds (wherein said acyclic unsaturated hydrocarbon may have at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl and phenoxy, and that 1 to 3 methylene groups therein may be replaced by a carbonyl group(s)), or C1-C14 linear or branched saturated or unsaturated hydrocarbon containing 1 to 5 thioether bonds, ether bonds andor amino bonds (with the proviso that a hetero atom does not directly binds to A, and wherein 1 to 3 methylene groups therein may be replaced by a carbonyl group(s));
R5 represents hydrogen or an organic group having a skeleton selected from those shown below
wherein Q represents NH, O, or S; T represents CH2, NH, S, or O; 1 represents an integer of 0 to 5; and m and n independently represent integers of 0 to 5, the total of m and n being not more than 5; each of said organic groups may have at least one substituent selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy;
R6 represents hydrogen: R7 represents hydrogen, hydroxy, C1-C5 alkoxy or C1-C5 alkanoyloxy; or R6 and R7 together represent \u2014O\u2014, \u2014CH2\u2014 or \u2014S\u2014;
R8 represents hydrogen, C1-C5 alkyl or C1-C5 alkanoyl; and
R12 and R13 both represent hydrogen, or one of them represents hydrogen and the other represents hydroxy, or they together represent oxo; and
the Formula (I) includes (+), (\u2212) and (\xb1) isomers
or a pharmaceutically acceptable acid addition salt thereof.
2. The method according to claim 1, comprising as the effective ingredient a compound represented by the Formula (I) wherein R1 is methyl, ethyl, propyl, butyl, isobutyl, cyclopropylmethyl, allyl, benzyl or phenethyl; R2 and R3 independently are hydrogen, hydroxy, acetoxy or methoxy; A is \u2014XC(\u2550Y)\u2014 (wherein X represents NR4, S or O, Y represents O, wherein R4 represents hydrogen or C1-C5 linear or branched alkyl), \u2014XC(\u2550Y)Z\u2014, \u2014X\u2014 or \u2014XSO2\u2014 (wherein X represents NR4, Y represents O or S, and Z represents NR4 or O, wherein R4 represents hydrogen or C1-C5 linear or branched alkyl); B is C1-C3 linear alkylene; R6 and R7 together form \u2014O\u2014; and R8 is hydrogen; or a pharmaceutically acceptable acid addition salt thereof.
3. The method according to claim 2, comprising as the effective ingredient a compound represented by the Formula (I) wherein A is \u2014XC(\u2550Y)\u2014 or \u2014XC(\u2550Y)Z\u2014 (wherein X represents NR4; Y represents O, and Z represents O, wherein R4 represents C1-C5 linear or branched alkyl); or a pharmaceutically acceptable acid addition salt thereof.
4. The method according to claim 3, comprising as the effective ingredient a compound represented by the Formula (I) wherein R5 is hydrogen or an organic group having a skeleton selected from those shown below
wherein Q represents O or S; each of said organic groups may have at least one substituent selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy; or a pharmaceutically acceptable acid addition salt thereof.
5. The method according to claim 4, comprising as the effective ingredient a compound represented by the Formula (I) wherein A is \u2014XC(\u2550Y)\u2014 or \u2014XC(\u2550Y)Z\u2014 (wherein X represents NR4, Y represents O, and Z represents O, wherein R4 represents C1-C5 linear or branched alkyl); or a pharmaceutically acceptable acid addition salt thereof.
6. The method according to claim 1, comprising as the effective ingredient a compound represented by the Formula (I) wherein R1 is methyl, ethyl, propyl, butyl, isobutyl, cyclopropylmethyl, allyl, benzyl or phenethyl; R2 and R3 independently are hydrogen, hydroxy, acetoxy or methoxy; A is \u2014XC(\u2550Y)\u2014 (wherein X represents NR4, and Y represents O, wherein R4 represents C1-C5 linear or branched alkyl); B is \u2014CH\u2550CH\u2014, \u2014C\u2261C\u2014, \u2014CH2O\u2014 or \u2014CH2S\u2014; R6 and R7 together form \u2014O\u2014; and R8 is hydrogen; or a pharmaceutically acceptable acid addition salt thereof.
7. The method according to claim 6, comprising as the effective ingredient a compound represented by the Formula (I) wherein R5 is hydrogen or an organic group having a skeleton selected from those shown below
wherein Q represents O or S; each of said organic groups may have at least one substituent selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy; or a pharmaceutically acceptable acid addition salt thereof.
8. The method, according to claim 6, comprising as the effective ingredient a compound represented by the Formula (I) wherein B is \u2014CH\u2550CH\u2014 or \u2014C\u2261C\u2014, or a pharmaceutically acceptable acid addition salt thereof.
9. The method according to claim 8, comprising as the effective ingredient a compound represented by the Formula (I) wherein R5 is hydrogen or an organic group having a skeleton selected from those shown below
wherein Q represents O or S; each of said organic groups may have at least one substituent selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy; or a pharmaceutically acceptable acid addition salt thereof.
10. The method according to claim 1, wherein said compound is a compound of the formula
11. A method for reducing pruritus caused by multiple sclerosis, said method comprising the steps of:
identifying a patient having pruritus caused by multiple sclerosis; and
administering to said patient a drug for prophylaxis or therapy of multiple sclerosis in combination with an effective amount of a compound represented by Formula (I):
wherein
represents a double bond or single bond;
R1 represents C1-C5 alkyl, C4-C7 cycloalkylalkyl, C5-C7 cycloalkenylalkyl, C6-C12 aryl, C7-C13 aralkyl, C4-C7 alkenyl, allyl, furan-2-ylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5) or thiophen-2-ylalkyl (wherein the number of carbon atoms in the alkyl moiety is 1 to 5);
R2 represents hydrogen, hydroxy, nitro, C1-C5 alkanoyloxy, C1-C5 alkoxy, C1-C5 alkyl or NR9R10 wherein R9 represents hydrogen or C1-C5 alkyl and R10 represents hydrogen or C1-C5 alkyl or \u2014C(\u2550O)R11 wherein R11 represents hydrogen, phenyl or C1-C5 alkyl;
R3 represents hydrogen, hydroxy, C1-C5 alkanoyloxy or C1-C5 alkoxy;
A represents \u2014XC(\u2550Y)\u2014, \u2014XC(\u2550Y)Z\u2014, \u2014X\u2014 or \u2014XSO2\u2014 (wherein X, Y and Z independently represent NR4, S or O wherein R4 represents hydrogen, C1-C5 linear or branched alkyl or C6-C12 aryl, and wherein R4s in the formula may be the same or different);
B represents valence bond, C1-C14 linear or branched alkylene (wherein said alkylene may have at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl and phenoxy, and that 1 to 3 methylene groups therein may be replaced by a carbonyl group(s)), C2-C14 linear or branched acyclic unsaturated hydrocarbon containing 1 to 3 double bonds andor triple bonds (wherein said acyclic unsaturated hydrocarbon may have at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, trifluoromethyl and phenoxy, and that 1 to 3 methylene groups therein may be replaced by a carbonyl group(s)), or C1-C14 linear or branched saturated or unsaturated hydrocarbon containing 1 to 5 thioether bonds, ether bonds andor amino bonds (with the proviso that a hetero atom does not directly binds to A, and wherein 1 to 3 methylene groups therein may be replaced by a carbonyl group(s));
R5 represents hydrogen or an organic group having a skeleton selected from those shown below
wherein Q represents NH, O, or S; T represents CH2, NH, S, or O; 1 represents an integer of 0 to 5; and m and n independently represent integers of 0 to 5, the total of m and n being not more than 5; each of said organic groups may have at least one substituent selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkanoyloxy, hydroxy, fluorine, chlorine, bromine, iodine, amino, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy;
R6 represents hydrogen: R7 represents hydrogen, hydroxy, C1-C5 alkoxy or C1-C5 alkanoyloxy; or R6 and R7 together represent \u2014O\u2014, \u2014CH2\u2014 or \u2014S\u2014;
R8 represents hydrogen, C1-C5 alkyl or C1-C5 alkanoyl; and
R12 and R13 both represent hydrogen, or one of them represents hydrogen and the other represents hydroxy, or they together represent oxo; and
the Formula (I) includes (+), (\u2212) and (\xb1) isomers
or a pharmaceutically acceptable acid addition salt thereof.