What is claimed is:
1. A proanthocyanidin composition substantially purified for one or more proanthocyanidin compounds with a peak located at about 95 ppm on 13C NMR.
2. The proanthocyanidin composition of claim 1 comprising one or more proanthocyanidin compounds having an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units.
3. The proanthocyanidin composition of claim 2, wherein said proanthocyanidin compounds consist of an average of four, five or six epicatechin flavanoid units.
4. A process for preparing a proanthocyanidin extract with a peak located at about 95 ppm on 13C NMR, said process comprising:
(a) homogenizing plant material in an aqueous extraction solvent comprising at least about 10% water but no more than about 30% water, about 10% to about 70% acetone, about 5% to about 60% methanol and about 0.05% to about 0.2% ascorbic acid to prepare a first extract;
(b) clarifying said first extract and obtaining a supernatant fraction therefrom;
(c) removing solvent from said supernatant fraction to obtain a residue and suspending said residue in distilled water to obtain an aqueous residue solution;
(d) subjecting said aqueous residue solution to further purification by either
(i) applying said aqueous residue solution to reverse-phase lipophilic chromatography material equilibrated in distilled water and successively washing said lipophilic chromatography material with a sufficient amount of distilled water to remove sugars, a sufficient amount of about 15% aqueous methanol to remove acids and a sufficient amount of 100% acidified methanol to elute polyphenolic compounds, and then removing solvent from said polyphenolic compounds to obtain a first dried fraction, or
(ii) extracting said aqueous residue solution with a non-polar extraction solvent, recovering the aqueous phase thereof and removing solvent from said aqueous phase to obtain a second dried fraction;
(e) suspending said first or second dried fraction in about 50% aqueous ethanol to obtain an ethanol solution, applying said ethanol solution to mixed hydrophilic-lipophilic chromatography material equilibrated in about 50% aqueous ethanol, and washing said mixed hydrophilic-lipophilic chromatography material with an amount of about 50% aqueous ethanol sufficient to remove non-proanthocyanidin polyphenolic compounds; and
(f) eluting said hydrophilic-lipophilic chromatography material with an amount of about 70% aqueous acetone sufficient to obtain said proanthocyanidin extract.
5. The process of claim 4, wherein said plant material is from a plant in the family Ericaceae or Vitaceae.
6. The process of claim 4, wherein said plant is a Vaccinium or Vitus species.
7. The process of claim 4, wherein said Vaccinium plant material is from Vaccinium macrocarpon.
8. A pharmaceutical composition comprising the proanthocyanidin extract of claim 1 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the proanthocyanidin composition produced by the process of claim 4 together with a pharmaceutically acceptable carrier.
10. A method of preventing or treating a urogenital infection in a mammal which method comprises administering a pharmaceutical composition according to claim 8 to said mammal in an amount and for a time sufficient to prevent, reduce or eliminate symptoms associated with said infection, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or (e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli.
11. The method of claim 10, wherein said mammal is a mink.
12. The method of claim 10, wherein said mammal is a human.
13. The method of claim 10, wherein said urogenital infection is a bladder infection or a kidney infection.
14. The method of claim 13, wherein said kidney infection is pyelonephritis.
15. A food composition comprising a consumable carrier in admixture with a proanthocyanidin composition substantially purified for one or more proanthocyanidin compositions selected from one or more of the following:
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; and
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli.
16. The food composition of claim 15 wherein said consumable carrier is animal feed.
17. A method of preventing or treating a urogenital infection in a livestock animal which method comprises administering the food composition of claim 16 to said animal in an amount and for a time to prevent, reduce or eliminate symptoms associated with said infection.
18. A method of reducing the pathogenicity of P-type E. coli in the digestive tracts of an animal which method comprises:
administering the food composition of claim 16 to the animal for a time and in an amount to reduce the detectable number of P-type E. coli bacterial cells in the feces or urine of said animal.
19. The method of claim 18, wherein said animal is a mammal.
20. A method of reducing P-type E. coli contamination in food which comprises:
(a) obtaining food; and
(b) adding the food composition of claim 15 to said food.
21. The method of claim 20 wherein said composition is added to said food before or during preparation of said food.
22. A method of reducing P-type E. coli contamination in food which comprises:
(a) obtaining an extract of a proanthocyanidin composition with a peak located at about 95 ppm on 13C NMR.
(b) obtaining food; and
(c) adding to said food one or more of the following:
(i) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli;
(ii) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iii) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iv) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(v) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli.
23. The method of claim 22 wherein said composition is added to said food before or during preparation of said food.
24. A method of preventing or treating a urogenital infection in a domesticated animal which comprises administering the food composition of claim 16 to said animal in an amount and for a time to prevent, reduce or eliminate symptoms associated with said infection.
25. The method of claim 24, wherein said animal is a mammal.
26. The food composition of claim 15 wherein said consumable carrier is a consumable food product.
27. The composition of claim 26, wherein said consumable food product is a cranberry-containing food product.
28. The composition of claim 27, wherein said cranberry-containing food product is a dried cranberry, a sweetened and dried cranberry, a flavored fruit piece, a sauce, a jelly, a relish, juice, wine or a cranberry juice-containing product.
29. The composition of claim 27, wherein said consumable food product is a beverage.
30. The composition of claim 29, wherein said beverage comprises cranberry juice, unpasteurized juice or pasteurized juice.
31. A method of preventing or treating a urogenital infection in a human which comprises administering a food composition of claim 26 to said human in an amount and for a time to prevent, reduce or eliminate symptoms associated with said infection.
32. A method of inhibiting adherence of P-type E. coli to a surface which comprises contacting said bacteria with at least one proanthocyanidin extract, compound or polymer, prior to or concurrently with contacting said bacteria with said surface, with the proanthocyanidin extract containing a peak located at about 95 ppm on a 13C NMR, wherein said proanthocyanidin extract, compound or polymer is selected from the group consisting of
(a) a substantially purified plant proanthocyanidin extract capable of inhibiting agglutination of P-type E. coli;
(b) a proanthocyanidin compound capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) a proanthocyanidin compound consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) a proanthocyanidin compound consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(e) a proanthocyanidin polymer capable of inhibiting agglutination of P-type E. coli.
33. The method of claim 32, wherein said surface is a uroepithelial cell surface or biofilm.
34. A method of reducing the incidence of infection after surgery, treating topical wounds or acne, or preventing or eliminating oral infection which comprises administering a pharmaceutical composition to a site of infection or potential infection in a patient, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR; or (e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli.
35. A method of detecting P-type reactive bacteria in a body fluid sample which comprises:
(a) contacting said body fluid sample with a P-type receptor-specific assay reagent and for a time and in an amount to allow binding of any P-type reactive bacteria present in said sample to said reagent, wherein said reagent comprises a solid-phase substrate coated with one or more proanthocyanidin extracts, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR compounds or polymers selected from the group consisting of
(i) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(ii) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(iii) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(iv) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR; or
(v) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR; and
(b) determining whether P-type reactive bacteria are present in said sample by assessing the degree of agglutination is said sample, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR.
36. The method of claim 35, wherein said plant extract is from a Vaccinium species.
37. The extract of claim 36, wherein said Vaccinium species is Vaccinium macrocarpon.
38. A method of detecting P-type reactive bacteria in a body fluid sample which comprises:
(a) testing said body fluid sample with human red blood cells in a agglutination assay;
(b) testing said body fluid sample with guinea pig blood cells in a second agglutination assay; and
(c) determining the results thereof.
39. A method of preventing or treating a urinary tract infection in a mammal which method comprises administering a pharmaceutical composition to said mammal in an amount and for a time sufficient to prevent, reduce or eliminate symptoms associated with said infection, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR; or
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR.
40. A method according to claim 39 wherein said proanthocyanidin extracts comprise of plant material from the family Vitaceae.
41. A method according to claim 40 wherein said Vitaceae plant material comprises of the Vitus species.
42. The proanthocyanidin composition of claim 1 comprising one or more proanthocyanidin compounds having an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units.
43. A method of preventing or treating a urogenital infection in a mammal which method comprises administering a pharmaceutical composition according to claim 8 to said mammal in an amount and for a time sufficient to prevent, reduce or eliminate symptoms associated with said infection, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. Coli;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli.
44. A food composition comprising a consumable carrier in admixture, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR, with one or more of the following:
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; and
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli.
45. A method of reducing P-type E. coli contamination in food, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR, which comprises:
(a) obtaining food; and
(b) adding to said food one or more of the following:
(i) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli;
(ii) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iii) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iv) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(v) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli.
46. A method of inhibiting adherence of P-type E. coli to a surface which comprises contacting said bacteria with at least one proanthocyanidin extract, compound or polymer, prior to or concurrently with contacting said bacteria with said surface, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR, wherein said proanthocyanidin extract, compound or polymer is selected from the group consisting of
(a) a substantially purified plant proanthocyanidin extract capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli;
(b) a proanthocyanidin compound capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) a proanthocyanidin compound consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) a proanthocyanidin compound consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(e) a proanthocyanidin polymer capable of inhibiting agglutination of P-type E. coli but incapable of inhibiting agglutination of type 1 E. coli.
47. A method of reducing the incidence of infection after surgery, treating topical wounds or acne, or preventing or eliminating oral infection which comprises administering a pharmaceutical composition to a site of infection or potential infection in a patient, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR; or
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E coli, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR.
48. A method of detecting P-type reactive bacteria in a body fluid sample which comprises:
(a) contacting said body fluid sample with a P-type receptor-specific assay reagent and for a time and in an amount to allow binding of any P-type reactive bacteria present in said sample to said reagent, wherein said reagent comprises a solid-phase substrate coated with one or more proanthocyanidin extracts, compounds or polymers, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR, selected from the group consisting of
(i) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli;
(ii) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iii) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(iv) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(v) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli; and
(b) determining whether P-type reactive bacteria are present in said sample by assessing the degree of agglutination is said sample, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR.
49. A method of preventing or treating a urinary tract infection in a mammal, wherein the proanthocyanidin extract contains a peak located at about 95 ppm on a 13C NMR, which method comprises administering a pharmaceutical composition to said mammal in an amount and for a time sufficient to prevent, reduce or eliminate symptoms associated with said infection, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier in admixture with one or more
(a) substantially purified plant proanthocyanidin extracts capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli;
(b) proanthocyanidin compounds capable of inhibiting agglutination of P-type E. coli, wherein said polymer comprises two or more flavanoid monomer units wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of any units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(c) proanthocyanidin compounds consisting of an average of from at least four to about seven epicatechin flavanoid units, wherein at least two of said units are linked together by an A-type interflavanoid linkage by bonds between C4 and C8 and between the C2 and the oxygen of C7 of the units and the remainder of the units are linked to each other by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units;
(d) proanthocyanidin compounds consisting of an average of from at least four to about twelve epicatechin flavanoid units, wherein each unit is linked to the next by a B-type interflavanoid bond between C4 and C8 or between C4 and C6 of the units; or
(e) proanthocyanidin polymers capable of inhibiting agglutination of P-type E. coli, but incapable of inhibiting agglutination of type 1 E. coli.
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 fabricating a semiconductor device comprising:
implanting first conduction type impurities into a semiconductor substrate to form a first well having a first conduction type;
implanting second conduction type impurities into the first well to form a second well having said first conduction type;
implanting second conduction type impurities into said second well, to form a second conduction type impurity region;
forming a gate on the semiconductor substrate; and
implanting second conduction type impurities in the second conduction type impurity region on one side of the gate.
2. The method as claimed in claim 1, wherein implanting second conduction type impurities into the first well to form a second well includes:
forming a first photoresist pattern on the semiconductor substrate having the first well therein, and
implanting the second conduction type impurities using the first photoresist pattern as a mask to form the second well.
3. The method as claimed in claim 2, wherein implanting the second conduction type impurities into the second well to form a second conduction type impurity region includes using the first photoresist mask to form the second conduction type impurity region.
4. The method as claimed in claim 1, wherein implanting second conduction type impurities into the first well to form a second well includes tilted injection of the second conduction type impurities using the first photoresist pattern as mask.
5. The method as claimed in claim 1, further comprising forming a source region in the first well on an opposite side of the gate relative to the second well.
6. The method as claimed in claim 1, wherein the drain region is spaced a predetermined distance away from the gate, sufficient to control a breakdown voltage of said semiconductor device.
7. The method as claimed in claim 1, wherein the first well has an impurity concentration higher than an effective impurity concentration of the second well.
8. The method of claim 1, wherein forming the gate on the semiconductor substrate comprises:
forming a gate dielectric layer on said substrate; and
forming a gate electrode thereon.
9. The method of claim 1, wherein said gate overlaps said second well and said second conduction type impurity region.
10. The method of claim 1, wherein said gate at least partially overlaps said second well.
11. The method of claim 1, wherein implanting said second conduction type impurities in said second conduction type impurity region includes:
forming a second photoresist pattern on the semiconductor substrate having the gate thereon, and
implanting the second conduction type impurities using the second photoresist pattern as a mask to form a drain region.
12. A semiconductor device, comprising:
a first well in a semiconductor substrate having a first conduction type and a first impurity concentration;
a second well in the first well having a first conduction type and a second impurity concentration;
a second conduction type impurity region in the second well having a third impurity concentration;
a gate insulating film and a gate electrode on the semiconductor substrate; and
a drain region formed in the second conduction type impurity region having a first conduction type and a fourth impurity concentration.
13. The semiconductor device as claimed in claim 12, wherein an effective impurity concentration of the second well is lower than the first impurity concentration of the first well.
14. The semiconductor device as claimed in claim 12, wherein the drain region is formed spaced a predetermined distance away from the gate electrode.
15. The semiconductor device as claimed in claim 12, further comprising a source region in the first well on an opposite side of the gate electrode relative to the second well.
16. The semiconductor device of claim 12, wherein said gate insulating film and gate electrode overlap said second well and said second conduction type impurity region.
17. The semiconductor device of claim 12, wherein said gate insulating film and gate electrode at least partially overlap said second well.
18. The semiconductor device of claim 12, wherein said first conduction type is p-type and said second conduction type is n-type.
19. The method of claim 1, wherein said first conduction type is p-type and said second conduction type is n-type.