Author: claimsbot

1. A method of sensitizing tumor cells to radiation, which method comprises
a) administering to said cells a camptothecin-based compound comprising one or more radiosensitizing electron-affinic groups, wherein the electron-affinic groups are selected from the group consisting of (+)-2-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)-propionic acid (TAPA), (\u2212)-2-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)-propionic acid (TAPA) and 2-(2,4,5,7-tetranito-9-flourenylidenaminooxy)-ethanoic acid (TNF-ethanoic acid).
2. A method for treating a cancer disorder in a subject having a tumor which method comprises administering to the subject a compound of the formula (II) or a pharmaceutically acceptable salt thereof,
wherein
X is S, \u2014NR\u2014, or a covalent bond;
Y is \u2550NO\u2014, \u2014N(H)O\u2014, \u2550N\u2014, \u2014NR\u2014, O, S, or a covalent bond;
T is independently CRR\u2032;
each of R and R\u2032 is independently selected from hydrogen, C1-4 alkyl, and substituted C1-4 alkyl;
n is an integer from 0 to 8;
R1 is optionally substituted fluorenyl; wherein the optional substituent(s) are independently selected from the group consisting of halo, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, and lower alkylcarbonylamino; provided that when X is a bond, Y is \u2550NO\u2014, \u2014N(H)O\u2014, \u2550N\u2014 or S;
R2 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, tri lower alkylsilyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, lower alkylcarbonylamino, lower alkylcarbonyloxy methyl, optionally substituted lower alkylcarbonyloxy methyl, substituted vinyl, 1-hydroxy-2-nitroethyl, alkoxycarbonylethyl, aminocarbonyl, alkylcarbonyl, alkylcarbonyloxymethyl, benzoylmethyl, benzylcarbonyloxymethyl, lower alkyliminomethyl or lower alkoxymethyl;
R3 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, CH2NR7 R8 (where each of R7 and R8 is independently H, alkyl of 1-6 carbons, optionally substituted phenyl, hydroxy lower alkyl, amino lower alkyl, or mono- or dialkylamino lower alkyl, or R7 and R8 taken together with \u2014N\u2014represent a cyclic amino-), CH2R9 (where R9 is lower alkoxy, CN, amino lower alkoxy, mono- or di-lower alkylamino lower alkoxy, lower alkylthio, amino lower alkylthio, or mono- or di-lower alkylamino lower alkylthio), NR10R11 (where each of R10 and R11 is independently hydrogen, lower alkyl, phenyl, hydroxy lower alkyl, or amino lower alkyl, or R10 and R11 taken together with \u2014N\u2014represent a cyclic amino), trialkylsilyl, dialkylamino alkyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino or R3 together with R4 is furan, dihydrofuran or 1,4-oxazine-2-one;
R4 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, amino lower alkyl, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino, or R4 together with R3 is furan, dihydrofuran or 1,4-oxazine-2-one, or R4 together with R5 is methylenedioxy;
R5 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino;
R6 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, trialkylsilyl, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino;
L is a bond or linear alkylene (1-8) group, optionally substituted with lower alkyl or substituted lower alkyl, wherein one or two methylene (\u2014CH2\u2014) units of the linear alkylene group is optionally replaced with O, S or NH; and
RQ is optionally substituted carbocyclic, heterocyclic, or fused 2-, 3- or 4-ring heterocyclic.
3. The method of claim 2, further comprising exposing the tumor in the subject to a unit dose of radiation.
4. The method of claim 2, wherein X is a covalent bond and Y is \u2550NO\u2014 or \u2014N(H)O\u2014.
5. The method of claim 4, wherein n is 1 and each of R and R\u2032 is independently methyl or hydrogen.
6. The method of claim 5, wherein R1, is substituted or unsubstituted 9-fluorenyl.
7. The method of claim 6, wherein the 9-fluorenyl is substituted with at least one nitro group.
8. The method of claim 6, wherein R1 is
9. The method of claim 2 wherein the compound is selected from the group consisting of:
10. The method of claim 2, wherein R1Y-(T)n, \u2014X\u2014C(O)O\u2014is
11. The method according to claim 2, wherein
R2 is hydrogen;
R3 is CH2NR7 R8 (where each of R7 and R8 is independently H, alkyl of 1-6 carbons, optionally substituted phenyl, hydroxy lower alkyl, amino lower alkyl, or mono-or dialkylamino lower alkyl, or R7 and R8 taken together with \u2014N\u2014represent a cyclic amino-), NR10R11 (where each of R10 and R11 is independently hydrogen, lower alkyl, phenyl, hydroxy lower alkyl, or amino lower alkyl, or R10 and R11 taken together with \u2014N\u2014 represent a cyclic amino), or dialkylamino alkyl;
R4 is lower alkoxy, hydroxy, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, or R4 together with R5 is methylenedioxy;
R5 is hydrogen or together with R4 is methylenedioxy; and
R6 is hydrogen.
12. The method of claim 11, wherein R3 is CH2NR7 R8 (where each of R7 and R8 is lower alkyl), R4 is hydroxy, alkoxy, lower alkoxycarbonyloxy or alkylcarbonyloxy, and R5 is hydrogen.
13. The method of claim 12, wherein R3 is CH2N(CH3)2.
14. The method of claim 13, wherein R4 is hydroxy.
15. The method of claim 2, wherein
R2 is hydrogen, lower alkyl or halogenated lower alkyl;
R3 is hydrogen or lower alkyl;
R4 is lower alkoxy, hydroxy, halogenated lower alkoxy, hydroxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, or R4 together with R5 is methylenedioxy;
R5 is hydrogen or together with R4 is methylenedioxy; and
R6 is hydrogen.
16. The method of claim 15, wherein R3 is hydrogen, R4 is carbamoyloxy, and R5 is hydrogen.
17. The method of claim 15, wherein R2 is lower alkyl and R4 is 4-(1-piperidino) -1-piperidinocarbonyloxy.
18. The method of claim 17, wherein R2 is ethyl.
19. The method of claim 18, wherein R2 is hydrogen, and R4 is 4-(1-piperidino)-1-piperidinocarbonyloxy.
20. The method of claim 15, wherein R2 is hydrogen, R3 is hydrogen and R4 is tert-butyloxycarbonyloxy.
21. The method of claim 2, wherein
R2 is lower alkyl;
R3 is hydrogen;
R4 is hydroxy, lower alkoxy, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, or lower alkoxycarbonyloxy;
R5 is hydrogen; and
R6 is hydrogen.
22. The method of claim 21, wherein R2 is ethyl and R4 is hydroxy.
23. The method of claim 2, wherein each of R2, R4, R5 and R6 is hydrogen and R3 is amino or nitro.
24. The method of claim 23, wherein R3 is amino.
25. The method of claim 23, wherein R3 is nitro.
26. The method of claim 2, wherein
R2 is tri-lower alkylsilyl;
R3 is hydrogen;
R4 is hydroxy, lower alkoxy, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, or lower alkoxycarbonyloxy;
R5 is hydrogen; and
R6 is hydrogen.
27. The method of claim 26, wherein R2 is t-butyldimethylsilyl and R4 is hydroxy.
28. The method of claim 2 wherein one of the R2, R4, or R5 is selected from the group consisting of (tris(hydroxymethyl)methylamino)methyl, (bis(hydroxymethyl)methylamino)methyl, and (2-hydroxyethylamino)methyl.
29. The method of claim 28 wherein R2 is selected from the group consisting of (tris(hydroxymethyl)methylamino)methyl, (bis(hydroxymethyl)methylamino)methyl, and (2-hydroxyethylamino)methyl.
30. The method of claim 29, wherein
R3 is hydrogen, dimethylamino, amino, or nitro;
R4 is hydrogen, hydroxy, or 4-(1-piperidino)-1-piperidinocarbonyloxy; or
R4 together with R5 is methylenedioxy;
R5 is hydrogen; or
R5 together with R4 is methylenedioxy; and
R6 is hydrogen.
31. The method of claim 30, wherein
R3 is hydrogen; and
R4 together with R5 is methylenedioxy, or
wherein each of R3, R4, and R5 is hydrogen.
32. The method of any one of claims 1, 2, and 28, wherein the compound is administered parenterally.
33. The method of any one of claims 1, 2, and 28, wherein the compound is administered intravenously.
34. The method of any one of claims 1, 2, and 28, wherein the compound is administered intramuscularly.
35. The method of any one of claims 1, 2, and 28, wherein the compound is administered orally.
36. The method of any one of claims 1, 2, and 28, wherein the compound is administered in the form of a liposomal composition.
37. The method of any one of claims 1, 2, and 28, wherein the compound is administered in the form of a micelle.
38. A method of sensitizing tumor cells to radiation, which method comprises
a) administering to said cells a compound of the formula (II) or a pharmaceutically acceptable salt thereof,
wherein
X is S, \u2014NR\u2014, or a covalent bond;
Y is \u2550NO\u2014, \u2014N(H)O\u2014, \u2550N\u2014, \u2014NR\u2014, O, S, or a covalent bond;
T is independently CRR1;
each of R and R\u2032 is independently selected from hydrogen, C1-4 alkyl, and substituted C1-4 alkyl;
n is an integer from 0 to 8;
R1 is optionally substituted fluorenyl; wherein the optional substituent(s) are independently selected from the group consisting of halo, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, and lower alkylcarbonylamino; provided that when X is a bond, Y is \u2550NO\u2014, \u2014N(H)O\u2014, \u2550N\u2014 or S;
R2 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, tri lower alkylsilyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, lower alkylcarbonylamino, lower alkylcarbonyloxy methyl, optionally substituted lower alkylcarbonyloxy methyl, substituted vinyl, 1-hydroxy-2-nitroethyl, alkoxycarbonylethyl, aminocarbonyl, alkylcarbonyl, alkylcarbonyloxymethyl, benzoylmethyl, benzylcarbonyloxymethyl, lower alkyliminomethyl or lower alkoxymethyl;
R3 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, CH2NR7 R8 (where each of R7 and R8 is independently H, alkyl of 1-6 carbons, optionally substituted phenyl, hydroxy lower alkyl, amino lower alkyl, or mono- or dialkylamino lower alkyl, or R7 and R8 taken together with \u2014N\u2014represent a cyclic amino-), CH2R9 (where R9 is lower alkoxy, CN, amino lower alkoxy, mono- or di-lower alkylamino lower alkoxy, lower alkylthio, amino lower alkylthio, or mono- or di-lower alkylamino lower alkylthio), NR10R11 (where each of R10 and R11 is independently hydrogen, lower alkyl, phenyl, hydroxy lower alkyl, or amino lower alkyl, or R10 and R11 taken together with \u2014N\u2014 represent a cyclic amino), trialkylsilyl, dialkylamino alkyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino or R3 together with R4 is furan, dihydrofuran or 1,4-oxazine-2-one;
R4 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, amino lower alkyl, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino, or R4 together with R3 is furan, dihydrofuran or 1,4-oxazine-2-one, or R4 together with R5 is methylenedioxy;
R5 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, 0-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino;
R6 is hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, RQY-L-C(O)O\u2014, cyano, nitro, amino, trialkylsilyl, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, O-quinone, substituted lower alkyl aminomethyl, or lower alkylcarbonylamino;
L is a bond or linear alkylene (1-8) group, optionally substituted with lower alkyl or substituted lower alkyl, wherein one or two methylene (\u2014CH2\u2014) units of the linear alkylene group is optionally replaced with O, S or NH; and
RQ is optionally substituted carbocyclic, heterocyclic, or fused 2-, 3- or 4-ring heterocyclic; and
b) exposing the tumor cells in the subject to a unit dose of radiation.
39. The method of claim 38, wherein X is a covalent bond and Y is \u2550NO\u2014 or \u2014N(H)O\u2014.
40. The method of claim 39, wherein n is 1 and each of R and R\u2032 is independently methyl or hydrogen.
41. The method of claim 40, wherein R1, is substituted or unsubstituted 9-fluorenyl.
42. The method of claim 41, wherein the 9-fluorenyl is substituted with at least one nitro group.
43. The method of claim 41, wherein R1 is
44. The method of claim 38 wherein the compound is selected from the group consisting of:
45. The method of claim 38, wherein R1Y\u2014(T)n\u2014X\u2014C(O)O\u2014is
46. The method according to claim 38, wherein
R2 is hydrogen;
R3 is CH2NR7 R8 (where each of R7 and R8 is independently H, alkyl of 1-6 carbons, optionally substituted phenyl, hydroxy lower alkyl, amino lower alkyl, or mono-or dialkylamino lower alkyl, or R7 and R8 taken together with \u2014N\u2014 represent a cyclic amino-), NR10R11 (where each of R10 and R11 is independently hydrogen, lower alkyl, phenyl, hydroxy lower alkyl, or amino lower alkyl, or R10 and R11 taken together with \u2014N\u2014 represent a cyclic amino), or dialkylamino alkyl;
R4 is lower alkoxy, hydroxy, halogenated lower alkyl, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, or R4 together with R5 is methylenedioxy;
R5 is hydrogen or together with R4 is methylenedioxy; and
R6 is hydrogen.
47. The method of claim 46, wherein R3 is CH2NR7 R8 (where each of R7 and R8 is lower alkyl), R4 is hydroxy, alkoxy, lower alkoxycarbonyloxy or alkylcarbonyloxy, and R5 is hydrogen.
48. The method of claim 47, wherein R3 is CH2N(CH3)2.
49. The method of claim 48, wherein R4 is hydroxy.
50. The method of claim 38, wherein
R2 is hydrogen, lower alkyl or halogenated lower alkyl;
R3 is hydrogen or lower alkyl;
R4 is lower alkoxy, hydroxy, halogenated lower alkoxy, hydroxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, lower alkoxycarbonyloxy, or R4 together with R5 is methylenedioxy;
R5 is hydrogen or together with R4 is methylenedioxy; and
R6 is hydrogen.
51. The method of claim 50, wherein R3 is hydrogen, R4 is carbamoyloxy, and R5 is hydrogen.
52. The method of claim 50, wherein R2 is lower alkyl and R4 is 4-(1-piperidino)-1-piperidinocarbonyloxy.
53. The method of claim 52, wherein R2 is ethyl.
54. The method of claim 53, wherein R2 is hydrogen, and R4 is 4-(1-piperidino)-1-piperidinocarbonyloxy.
55. The method of claim 50, wherein R2 is hydrogen, R3 is hydrogen and R4 is tert-butyloxycarbonyloxy.
56. The method of claim 38, wherein
R2 is lower alkyl;
R3 is hydrogen;
R4 is hydroxy, lower alkoxy, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, lower alkylcarbonyloxy, or lower alkoxycarbonyloxy;
R5 is hydrogen; and
R6 is hydrogen.
57. The method of claim 56, wherein R2 is ethyl and R4 is hydroxy.
58. The method of claim 38, wherein each of R2, R4, R5 and R6 is hydrogen and R3 is amino or nitro.
59. The method of claim 58, wherein R3 is amino.
60. The method of claim 58, wherein R3 is nitro.
61. The method of claim 38, wherein
R2 is tri-lower alkylsilyl;
R3 is hydrogen;
R4 is hydroxy, lower alkoxy, halogenated lower alkoxy, hydroxycarbonyl, formyl, lower alkoxycarbonyl, carbamoyloxy, lower alkylcarbonyloxy, or lower alkoxycarbonyloxy;
R5 is hydrogen; and
R6 is hydrogen.
62. The method of claim 61, wherein R2 is t-butyldimethylsilyl and R4 is hydroxy.
63. The method of claim 38 wherein one of the R2, R4, or R5 is selected from the group consisting of (tris(hydroxymethyl)methylamino)methyl, (bis(hydroxymethyl)methylamino)methyl, and (2-hydroxyethylamino)methyl.
64. The method of claim 63 wherein R2 is selected from the group consisting of (tris(hydroxymethyl)methylamino)methyl, (bis(hydroxymethyl)methylamino)methyl, and (2-hydroxyethylamino)methyl.
65. The method of claim 64, wherein
R3 is hydrogen, dimethylamino, amino, or nitro;
R4 is hydrogen, hydroxy, or 4-(1-piperidino)-1-piperidinocarbonyloxy; or
R4 together with R5 is methylenedioxy;
R5 is hydrogen; or
R5 together with R4 is methylenedioxy; and
R6 is hydrogen.
66. The method of claim 65, wherein
R3 is hydrogen; and
R4 together with R5 is methylenedioxy, or
wherein each of R3, R4, and R5 is hydrogen.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

What we claim is:

1. A confectionery product comprising:
(i) a salivation region comprising a salivation agent in an amount effective to aid in the stimulation of the flow of saliva in an oral cavity and a salivation region confectionery base; and
(ii) an oral comfort region that is separate and distinct from said salivation region, said oral comfort region comprising an oral comfort ingredient in an amount effective to lubricate, coat or moisten said oral cavity and an oral comfort region confectionery base.
2. The confectionery product according to claim 1, wherein said salivation region confectionery base and said oral comfort region confectionery base are sugar bases.
3. The confectionery product according to claim 2, wherein said sugar bases comprises a sugar selected from the group consisting of sucrose, glucose, fructose, maltose, corn syrup and mixtures thereof.
4. The confectionery product according to claim 1, wherein said salivation region confectionery base and said oral comfort region confectionery base are sugarless bases.
5. The confectionery product according to claim 4, wherein said sugarless bases are selected from group consisting of isomalt, erythritol, hydrogenated starch hydrolysates, sorbitol, xylitol, mannitol and mixture thereof.
6. A confectionery product according to claim 1, wherein said salivation agent is selected from the group consisting of acidulents, cooling compounds, salts, salt enhancers, monosodium glutamate, monosodium glutamate enhancers, flavors and mixtures thereof.
7. A confectionery product according to claim 6, wherein said acidulent is selected from the group consisting of citric acid, malic acid, succinic acid, adipic acid and mixtures thereof.
8. The confectionery product according to claim 1, wherein said salivation agent is present in an amount from about 0.01% to about 4% by weight of the confectionery product.
9. The confectionery product according to claim 1, wherein said oral comfort ingredient is selected from the group consisting of lipids, proteins, surfactants and mixtures thereof.
10. The confectionery product according to claim 9, wherein said oral comfort ingredient is a lipid.
11. A confectionery product according to claim 10, wherein said lipid is present in an amount of about 1 to about 20% by weight of the confectionery product.
12. The confectionery product according to claim 10, wherein said lipid is selected from the group consisting of partially hydrogenated palm kernel oil, medium chain triglycerides, coconut oil, anhydrous milk fat, cocoa butter, corn oil, palm oil, soybean oil, sunflower oil, canola oil and mixtures thereof.
13. The confectionery product according to claim 10, wherein said oral comfort region further comprises a surfactant selected from the group consisting of nonionic surfactants, anionic surfactants and amphoteric surfactants.
14. The confectionery product according to claim 13, wherein said surfactant is present in an amount of about 0.5 percent to about 4 percent by weight of said oral comfort region.
15. The confectionery product according to claim 1, wherein said salivation region comprises an acidulent and a cooling compound.
16. The confectionery product according to claim 15, wherein said cooling compound is present in an amount of about 0.01 to 0.2% by weight of the confectionery product.
17. A method of preparing a confectionery product having a salivation region and oral comfort region that is separate and distinct from said salivation region, said method comprising the steps of:
(i) mixing a salivation region with a salivation region confectionery base to form a salivation agent containing confectionery base;
(ii) mixing an oral comfort ingredient with a oral comfort region confectionery base to form a oral comfort ingredient containing confectionery base; and
(iii) forming said confectionery product with said salivation agent containing confectionery base and said oral comfort ingredient containing confectionery base in a manner that maintains said salivation agent containing confectionery base and said oral comfort ingredient containing confectionery base in separate and distinct regions of said confectionery product.
18. The method according to claim 17, wherein said step of forming comprises substantially simultaneously depositing said salivation agent containing confectionery base and said oral comfort ingredient containing confectionery base in separate and distinct regions of a confectionery mold.
19. The method according to claim 18, wherein said confectionery mold has a raised ridge running along its bottom inner surface that defines said separate and distinct regions of said confectionery mold.
20. A method for treating xerostomia, which comprises:
introducing into the oral cavity a confectionery product containing a confectionery base, a salivation agent concentrated in one region of said product, and an oral comfort ingredient concentrated in a separate region of said product.
21. A method according to claim 20, wherein said salivation agent is an acidulent in combination with a cooling compound.

1. A common key generating method for generating a common key for use in an encryption process of encrypting a plaintext into a ciphertext and a decryption process of decrypting the ciphertext into the plaintext in cryptographic communication between entities, comprising the steps of:
dividing identification information of one entity into a plurality of blocks to obtain divided identification information;
generating secret keys of the one entity by using the respective divided identification information;
extracting components corresponding to other entity as a communicating party from the generated secret keys of the one entity; and
generating a common key by performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
2. The common key generating method as set forth in claim 1,
wherein a shift composition is used in performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
3. A common key generating apparatus, provided for an entity in a cryptographic communication system, for generating a common key for use in an encryption process of encrypting a plaintext into a ciphertext and a decryption process of decrypting the ciphertext into the plaintext, comprising
a controller capable of performing the following operations:
(i) extracting, from secret keys of the entity generated using respective divided identification information obtained by dividing identification information of the entity into a plurality of blocks, components corresponding to other entity as a communicating party; and
(ii) generating a common key by performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
4. The common key generating apparatus as set forth in claim 3,
wherein a shift composition is used in performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
5. An encryption method for encrypting into a ciphertext a plaintext to be transmitted from a first entity to a second entity, comprising the steps of:
generating secret keys of the first entity by using respective divided identification information obtained by dividing identification information of the first entity into a plurality of blocks;
generating a common key by extracting components corresponding to the second entity from the generated secret keys and performing composition of the extracted components after converting the extracted components to increase the number of bits thereof; and
encrypting the plaintext into the ciphertext by using the generated common key.
6. A cryptographic communication method for communicating information by a ciphertext between first and second entities, comprising the steps of:
sending secret keys generated using respective divided identification information obtained by dividing identification information of each entity into a plurality of blocks to each of the first and second entities from a plurality of key generating agencies;
at the first entity, generating a first common key by extracting components corresponding to the second entity as a destination of the ciphertext from the respective secret keys of the first entity sent from the respective key generating agencies and performing composition of the extracted components after converting the extracted components to increase the number of bits thereof;
at the first entity, encrypting a plaintext into a ciphertext by using the generated first common key and transmitting the ciphertext to the second entity;
at the second entity, generating a second common key identical with the first common key by extracting components corresponding to the first entity from the respective secret keys of the second entity sent from the respective key generating agencies and performing composition of the extracted components after converting the extracted components to increase the number of bits thereof; and
at the second entity, decrypting the transmitted ciphertext into a plaintext by using the generated second common key.
7. The cryptographic communication method as set forth in claim 6,
wherein a shift composition is used at the first and second entities in performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
8. A cryptographic communication system for performing an encryption process of encrypting a plaintext as information to be transmitted into a ciphertext and a decryption process of decrypting the transmitted ciphertext into a plaintext mutually between a plurality of entities, comprising:
a plurality of key generating agencies, each of which generates a secret key of each entity, by using each of respective divided identification information obtained by dividing identification information of each entity into a plurality of blocks and for transmitting the generated secret key to each entity; and
a plurality of entities, each of which generates a common key for use in the encryption process and decryption process by extracting components corresponding to other entity as a communicating party from its own secret keys sent from the key generating agencies and performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
9. A computer memory product having computer readable program code means for causing a computer to generate a common key for use in an encryption process of encrypting a plaintext into a ciphertext and a decryption process of decrypting the ciphertext into the plaintext in cryptographic communication between entities, said computer readable program code means comprising:
program code means for causing the computer to extract from secret keys of one entity, which were generated using respective divided identification information obtained by dividing identification information of the one entity into a plurality of blocks, components corresponding to other entity as a communicating party; and
program code means for causing the computer to generate a common key by performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.
10. A computer data signal embodied in a carrier wave for transmitting a program, the program being configured to cause a computer to generate a common key for use in an encryption process of encrypting a plaintext into a ciphertext and a decryption process of decrypting the ciphertext into the plaintext in cryptographic communication between entities, comprising:
a code segment for causing the computer to extract from secret keys of one entity, which were generated using respective divided identification information obtained by dividing identification information of the one entity into a plurality of blocks, components corresponding to other entity as a communicating party; and
a code segment for causing the computer to generate a common key by performing composition of the extracted components after converting the extracted components to increase the number of bits thereof.

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 surgical method for recovering or protecting a joint cartilage from a degenerative andor inflammatory pathology, associated with the production of IL-1, selected from osteoarthritis, psoriatic and rheumatoid arthritis, said method comprising the step of implanting into a subject in need thereof a graft consisting essentially of a biological material containing:
a) a three-dimensional matrix based on a hyaluronic acid derivative in the form of a non-woven tissue and selected from the class of hyaluronic acid benzyl esters having a percentage of esterification ranging from 75 to 100%; and optionally
b) chondrocytes andor mesenchymal cells partially or completely differentiated towards chondrocytes.
2. The method according to claim 1, wherein the biological material contains said cells (b), said graft being an in vitro cartilage tissue to be surgically implanted in vivo inside the joint capsule wherein the extracellular cartilage matrix is degraded by said pathology.
3. The method according to claim 2, wherein said graft further consists essentially of the extracellular matrix produced by said b) chondrocytes andor mesenchymal cells partially or completely differentiated towards chondrocytes, said extracellular matrix being both within said graft and inside the joint cartilage after the graft implantation.
4. The method according to claim 1, wherein said graft is surgically implanted at the beginning of the process of degradation of the extracellular matrix of the cartilage.
5. The method according to claim 1, wherein said graft is surgically implanted at later stages of said pathology.
6. The method according to claim 1, wherein the average molecular weight of hyaluronic acid in the hyaluronic acid derivative range between 1\xd7105 Da and 1\xd7106 Da.
7. The method according to claim 6, wherein the average molecular weight of hyaluronic acid range between 200,000 and 750,000 Da.
8. The method according to claim 1, wherein the hvaluronic acid derivative has a percentage of esterification ranging from 75 to 100%, and the remaining percentage of unesterified hyaluronic acid is salified with an organic or inorganic base.
9. The method according to claim 8, wherein said base is sodium hydroxide.