1. A stick or soft solid suspension product comprising:
(a) 0.01-20 weight % of a polyacrylate superabsorbent polymer (sodium salt), with a salt or ionic strength tolerance under a Baseline Absorption Test sufficient to give at least 25 weight % water absorption;
(b) 10-88 weight % of a volatile silicone having a flash point of 100 degrees C. or less; and
(c) a gelling agent selected from the group consisting of 5-30 weight % stearyl alcohol; 0.1-20 weight % waxes; 0.1-10 weight % (on an actives basis) silicone elastomer; 0.1-3 weight % siliconized polyamides; 0.1-20 weight % low molecular weight polyethylene having a molecular weight in the range of 400-1000 and combinations of the foregoing.
2. A product according to claim 1 further comprising one or more ingredients selected from the group consisting of:
(d) 0-5 weight % of a surfactant with a hydrophiliclipophilic balance in the range of 3-13;
(e) 0-25 weight % of an antiperspirant active or. an effective amount of a deodorizing agent which is not an antiperspirant active;
(f) 0-20 weight % of a nonvolatile silicone having a flash point greater than 100 degrees C.; and
(g) 0-20 weight % of an emollient;
provided that the water content is \u22662 weight % and the ratio of superabsorber to active salt is in the range of 0.13-4:1.
3. A product according to claim 1 comprising 0.1-10% of the superabsorbent polymer.
4. A product according to claim 1 comprising 0.5-5% of the superabsorbent polymer.
5. A product according to claim 1 wherein the volatile silicone is a D4-D6 cyclomethicone.
6. A product according to claim 1 comprising one or both of D5 and D6 cyclomethicones as the volatile silicone.
7. A product according to claim 1 wherein the wax is Japan wax or a hydrogenated castor oil.
8. A product according to claim 1 wherein the surfactant comprises about from 0.05-50 weight % of a silicone copolyol at a concentration of 10% in cyclomethicone, or an equivalent amount of silicone copolyol using a different dilution factor.
9. A product according to any one of claims 1-8 further comprising 5-10% of an antiperspirant active.
10. A product according to claim 1 comprising 5-10% of the nonvolatile silicone.
11. A product according to claim 1 comprising 2-12% of the emollient.
12. A product according to claim 1 wherein the emollient is selected from the group consisting of C12-15 alkyl benzoate, PPG-3-myristyl ether, and polyisobutene 250 and comprises 2-12 weight % of the product.
13. A cosmetic product according to claim 1 further comprising an effective amount of a deodorizing agent which is not an antiperspirant active.
14. A cosmetic product according to claim 1 comprising 5-30 weight % stearyl alcohol as the gelling agent.
15. A cosmetic product according to claim 1 comprising 0.1-20 weight % waxes selected from the group consisting of Japan wax, hydrogenated castor oil with a melting point in the range of 50-90 degrees C. and mixtures thereof.
16. A cosmetic product according to claim 1 comprising a silicone elastomer as the gelling agent.
17. A product according to claim 1 comprising a low molecular weight polyethylene having a molecular weight in the range of 400-1000 as the gelling agent.
18. A product according to claim 1 comprising as the gelling agent a siliconized polyamide of Formula IIIA:
where:
(1) DP is a number in the range of 10-40;
(2) n is a number selected from the group consisting of 1-500;
(3) X is a linear or branched chain alkylene having 1-30 carbons;
(4) Y is selected from the group consisting of linear and branched chain alkylenes having 1-40 carbons, wherein:
(A) the alkylene group may optionally and additionally contain in the alkylene portion at least one of the members of a group consisting of (i) 1-3 amide linkages; (ii) C5 or C6 cycloalkane (as a cycloalkylene linkage); and (iii) phenylene optionally substituted by 1-3 members selected independently from the group consisting of C1-C3 alkyls; and
(B) the alkylene group itself may optionally be substituted by at least one member selected from the group consisting of (i) hydroxy; (ii) C3-C8 cycloalkane; (iii) 1-3 members selected independently from the group consisting of C1-C3 alkyls; phenyl optionally substituted by 1-3 members selected independently from the group consisting of C1-C3 alkyls; (iv) C1-C3 alkyl hydroxy; and (v) C1-C6 alkyl amine; or y=Z2 where
wherein each of R 20, R21 and R22 are independently selected from the group consisting of linear and branched C1-C10 alkylenes; and T is selected from the group consisting of (i) a trivalent atom selected from N, P and Al; and (ii) \u2014CR, where R is selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, a siloxane chain, and phenyl, wherein the phenyl may optionally be substituted by 1-3 members from the group consisting of methyl and ethyl; and
(5) each of R1-R4 is independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, a siloxane chain, and phenyl, wherein the phenyl may optionally be substituted by 1-3 members from the group consisting of methyl and ethyl; wherein the polyamide of Formula IIIA has:
(i) a silicone portion in the acid side of the polyamide;
(ii) a degree of polymerization in the range of 10-40;
(iii) an average molecular weight of at least 50,000 daltons with at least 95% of the polyamide having a molecular weight greater than 10,000 daltons; and
(iv) a polydispersity of less than 20.
19. A product according to any one of claims 1-8 and 10-18 wherein the ratio of superabsorbent polymer to active salt is in the range of 0.18-4:1.
20. A product according to any one of claims 1-8 and 10-18 wherein the superabsorbent polymer has a particle size not exceeding 100 microns.
21. A product according to any one of claims 1-8 and 10-18 wherein the superabsorbent polymer has a particle size \u226675 microns.
22. A product according to any one of claims 1-8 and 10-18 wherein the superabsorbent polymer has a particle size in the range of 6-65 microns with no more than 10% of the particles having a size less than 6 microns.
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 compound having the chemical formula:
87
wherein R1 is selected from the group consisting of: heteroaryl and heterocycloalk;
R2 is selected from the group consisting of: lower alk, cycloalk, alkoxy, H, OH, O. C(O)OH, C(O)O-lower alk, C(O)NH-lower alk, C(O)N(lower alk)2, SH, S-lower alk, NH2, NH-lower alk, and N(lower alk)2,
R3 and R4 is each independently lower alk or together cyclopropyl;
R5 is either an optionally substituted naphthyl having one to four substituents independently selected from the group consisting of methyl, ethyl, isopropyl, methoxy, Cl, F, Br, and lower haloalkoxy, or a substituted phenyl having one to four substituents with at least one substituent in a meta or para position selected from the group consisting of: lower alkyl, methoxy, Cl, F, Br, and lower haloalkoxy, provided that said substituted phenyl may also have 2 to 3 additional substituents;
R6 if present is either hydrogen, lower alkyl or lower alkenyl, wherein R6 is not present if R2 is O;
Y1 is either covalent bond, alkylene, or alkenylene;
Y2 is alkylene;
Y3 is alkylene;
Z is selected from the group consisting of: covalent bond, O, S, NH, N-lower alk, alkylene, alkenylene, and alkynylene, provided that if Z is either O, S, NH, or N-lower alk, then Y1 is not a covalent bond; further provided that Y1 and Z may together be a covalent bond;
further provided that if R5 is 3,4 dimethoxy-phenyl, then R1 is not CH3(CH2)5O-phenyl; 2-cyclopentyl, phenyl; 2-Cl-phenyl; 2-CN-phenyl; 2-(3-furanyl)phenyl; or 4-benzo(d)isothiazole;
further provided that if R5 is 4-methoxy-phenyl, then R1 is not 2-cyclopentyl-phenyl; 2-CH3-phenyl; 2-benzyl-phenyl; 3-CH3-phenyl, 4-CH3SO2-phenyl, 4-benzo(d)isothiazole;
further provided that if R5 is 4-Cl-phenyl, then R1 is not 2-CH3-phenyl, 5-iso-propyl-phenyl; 4-CH3-phenyl; phenyl; 2-Cl-phenyl; 4-Cl-phenyl; 2-methoxy, 4-CH3CHCH-phenyl; 3,4 CH3-phenyl, 2,4 CH3-phenyl; 2,3 CH3-phenyl; 2-iso-propyl, 5-CH3-phenyl; pyridyl; 1-imidazole; or 4-benzo(d)isothiazole; and
further provided that if R5 is 3,5 dimethyl, 4-methoxy-phenyl, then R1 is not 4-CH3, 6-CN-2-pyridyl; or thiophenecarboxamide; and
pharmaceutically acceptable salts and complexes thereof;
wherein said compound has an IC5010 M using the Calcium Receptor Inhibitor Assay.
2. The compound of claim 1, wherein
Y1 is methylene;
Y2 is methylene; and
Y3 is methylene.
3. The compound of any of claims 1-2, wherein
R2 is OH or methoxy,
R6 is hydrogen,
R3 or R4 is independently methyl or ethyl; and
Z is O, S, or unsubstituted alkylene.
4. The compound of claim 3, wherein R2 is OH, and Z is O.
5. The compound of claims 1-2, wherein
R2 is hydrogen,
R6 is hydrogen,
R3 and R4 is independently methyl or ethyl; and
Z is O or methylene.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claims 1-3.
7. A method of treating a patient comprising the step of administering to said patient a therapeutically effective amount of a compound having the formula:
88
wherein R1 is selected from the group consisting of: heteroaryl and heterocycloalk;
R2 is selected from the group consisting of: lower alk, cycloalk, alkoxy, H, OH, O, C(O)OH, C(O)O-lower alk, C(O)NH-lower alk, C(O)N(lower alk)2, SH, S-lower alk, NH2, NH-lower alk, and N(lower alk)2;
R3 and R4 is each independently lower alk or together cyclopropyl;
R5 is aryl;
R6 if present is either hydrogen, lower alkyl or lower alkenyl, wherein R6 is not present if R2 is O;
Y1 is either covalent bond, alkylene, or alkenylene;
Y2 is alkylene;
Y3 is alkylene;
Z is selected from the group consisting of: covalent bond, O, S, NH, N-lower alk, alkylene, alkenylene, and alkynylene, provided that if Z is either O, Z, NH, or N-lower alk, then Y1 is not a covalent bond; further provided that Y1 and Z may together be a covalent bond; and
pharmaceutically acceptable salts and complexes thereof;
wherein said patient has a disease or disorder characterized by one or more of the following: (1) an abnormal bone or mineral homeostasis; (2) an abnormal amount of an extracellular or intracellular messenger which is ameliorated by a compound able to effect one or more calcium receptor activities; or (3) an abnormal effect of an intracellular or extracellular messenger which is ameliorated by a compound able to affect one or more calcium receptor activities.
8. The method of claim 7, wherein said disease or disorder is characterized by said abnormal bone or mineral homeostasis.
9. The method of claim 7, wherein said disease or disorder is selected from the group consisting of: osteosarcoma, periodontal disease, fracture healing, osteoarthritis, rheumatoid arthritis, Paget’s disease, humoral hypercalcemia malignancy, and osteoporosis.
10. The method of claim 9, wherein disease or disorder is osteoporosis.
11. A method of treating a patient comprising the step of administering to said patient an amount of a compound sufficient to increase serum PTH level, said compound having the formula:
89
wherein R1 is selected from the group consisting of: heteroaryl and heterocycloalk;
R2 is selected from the group consisting of: lower alk, cycloalk, alkoxy, H, OH, O, C(O)OH, C(O)O-lower alk, C(O)NH-lower alk, C(O)N(lower alk)2, SH, S-lower alk, NH2, NH-lower alk, and N(lower alk)2;
R3 and R4 is each independently lower alk or together cyclopropyl;
R5 is aryl;
R6 if present is either hydrogen, lower alkyl or lower alkenyl, wherein R6 is not present if R2 is O;
Y1 is either covalent bond, alkylene, or alkenylene;
Y2 is alkylene;
Y3 is alkylene
Z is selected from the group consisting of: covalent bond, O, S, NH, N-lower alk, alkylene, alkenylene, and alkynylene, provided that if Z is either O, S, NH, or N-lower alk, then Y, is not a covalent bond; further provided that Y1 and Z may together be a covalent bond; and
pharmaceutically acceptable salts and complexes thereof.
12. The method of claim 11, wherein said compound is administered to said patient causes an increase in serum PTH having a duration of one to twelve hours.
13. The method of claim 11, wherein said method is carried out by administering an amount of said compound effective causes an increase in either duration, quantity, or both duration and quantity, of serum PTH level sufficient to have a therapeutic effect.
14. The method of claim 13, wherein said compound is administered to said patient causes an increase in serum PTH having a duration of one to twelve hours.
15. The method of claim 14, wherein said duration is about two to about four hours.
16. The method of claim 13, wherein said compound is administered to said patient causes an increase in serum PTH up to 0.5 fold greater than peak serum PTH in said patient.
17. The method of claim 13, wherein said compound is administered to said patient causes an increase in serum PTH 0.5 fold to 5 fold greater than peak serum PTH in said patient.
18. The method of claim 13, wherein said compound is administered to said patient causes an increase in serum PTH 5 fold to 10 fold greater than peak serum PTH in said patient.
19. The method of claim 13, wherein said compound is administered to said patient causes an increase in serum PTH at least 10 fold greater than peak serum PTH in said patient.
20. The method of any of claims 7-19, wherein R5 is a substituted phenyl having one to four substituents each independently selected from the group consisting of: methoxy, lower alkyl, OCF3, CFH2, CHF2, CF3, OHC2CF3, F, Cl, Br, I, OH, SH, CN, NO2, NH2, methylene dioxy, NH-lower alkyl, N(lower alkyl)2, C(O)lower alkyl, SC(O)lower alkyl, S(O)2 lower alkyl, OC(O)lower alkyl, SC(O)lower alkyl, OC(S)lower alkyl, NHC(O)lower alkyl, N(lower alkyl)C(O)lower alkyl, NHC(S) lower alkyl, N(lower alkyl)C(S)lower alkyl, NHS(O)lower alkyl, N(lower alkyl)S(O)lower alkyl, C(O)OH, C(O)O-lower alkyl, C(O)NH2, C(O)NH-lower alkyl, C(O)N(lower alkyl)2, S(O)2NH2, S(O)2NH-lower alkyl, and S(O)2N(lower alkyl)2.
21. The method of claim 20, wherein each R5 substituent is independently selected from the group consisting of: alkoxy, lower-haloalkyl, S-unsubstituted alkyl, lower-haloalkoxy, unsubstituted alkyl, unsubstituted alkenyl, halogen, SH, CN, NO2, NH2 and OH.
22. The method of claim 21, wherein R5 is a substituted phenyl with at least one substituent in a meta or para position selected from the group consisting of: lower alkyl, methoxy, Cl, F, Br, and lower haloalkoxy, provided that said R5 substituted phenyl may also have 2 to 3 additional substituents.
23. The method of claim 9 or 13, wherein R5 is an optionally substituted naphthyl.
24. The method of claim 23, wherein R5 is a substituted naphthyl having one to four substituents each independently selected from the group consisting of: alkoxy, lower-haloalkyl, S-unsubstituted alkyl, lower-haloalkoxy, unsubstituted alkyl, unsubstituted alkenyl, halogen, SH, CN, NO2, NH2 and OH.
25. The method of claim 24, wherein R5 is naphthyl.
26. The method of claim 22, wherein
R2 is OH or alkoxy,
R6 is hydrogen,
R3 and R4 is each independently a lower alkyl; and
Z is either O, S, or unsubstituted alkylene.
27. The method of claim 26, wherein
R2 is OH or methoxy;
Y1 is methylene;
Y2 is methylene; and
Y3 is methylene.
28. The method of claim 27, wherein R3 is methyl or ethyl; and R4 is methyl or ethyl.
29. The method of claim 28, wherein Z is O or methylene and R2 is OH.
30. A method of screening for a calcilytic compound comprising the step of measuring the ability of a compound to inhibit one or more calcium receptor activities, said compound having the formula:
90
wherein R1 is selected from the group consisting of: heteroaryl and heterocycloalk;
R2 is selected from the group consisting of: lower alk, cycloalk, alkoxy, H, OH, O, C(O)O-lower alk, C(O)NH-lower alk, C(O)N(lower alk)2, SH, S-lower alk, NH2, NH-lower alk, and N(lower alk)2;
R3 and R4 is each independently lower alk or together cyclopropyl;
R5 is aryl;
R6 if present is either hydrogen, lower alkyl or lower alkenyl, wherein R6 is not present if R2 is O;
Y1 is either covalent bond, alkylene, or alkenylene;
Y2 is alkylene;
Y3 is alkylene;
Z is selected from the group consisting of: covalent bond, O, S, NH, N-lower alk, alkylene, alkenylene, and alkynylene, provided that if Z is either O, S, NH, or N-lower alk, then Y1 is not a covalent bond; further provided that Y1 and Z may together be a covalent bond; and
pharmaceutically acceptable salts and complexes thereof.
31. The method of claim 30, wherein said method is carried out under conditions wherein influx of extracellular Ca2 is inhibited.