Materials and Methods for Improving Gastrointestinal Function

• US 20120077748A1
• Filed: 09/26/2011
• Published: 03/29/2012
• Est. Priority Date: 09/24/2010
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: Zhang, Lurong, VIDYASAGAR, Sadasivan, Okunieff, Paul
• Granted Patent: US 8,993,522 B2
• Time in Patent Office: Days
• US Class Current: 514/13.2
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/32 having an effect on the health of the digestive tract
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 1/12 Antidiarrhoeals

Abstract

The subject invention provides therapeutic compositions, and uses thereof for the treatment or amelioration of injury to small intestine mucosa. In preferred embodiments, the composition comprises one or more nutrients and/or electrolytes that acquire or retain considerable absorptive capacity.

Claims

1. A sterile therapeutic composition for improving small intestine health, in particular in the case of villous atrophy, wherein the composition is formulated for enteral administration and comprises lysine, glycine, threonine, valine, and tyrosine, as free amino acids;

and water; and

wherein the composition has a total osmolarity from 230 mosm to 280 mosm.

2. The therapeutic composition according to claim 1, wherein the composition does not comprise one or more ingredients selected from glucose, glutamine, and methionine, or, if these ingredients are present, glucose is present at a concentration of less than 1 g/l, glutamine is present at a concentration of less than 300 mg/l, and methionine is present at a concentration of less than 300 mg/l.

3. The therapeutic composition according to claim 2, further comprising aspartic acid, isoleucine, tryptophan, asparagine, and/or serine.

4. The therapeutic composition according to claim 1, wherein the composition does not comprise glucose, glutamine, or methionine.

5. The composition, according to claim 1, wherein the composition further comprises electrolytes, vitamins, minerals, and/or flavoring agents.

6. A method for treating a subject having villous atrophy, wherein the method comprises administering to the subject, via enteral administration, a composition of claim 1.

7. The method according to claim 6, wherein the subject is a human.

8. The method according to claim 6, wherein the subject has at least a 10% reduction in total number of small intestinal epithelial cells in the villous region, when compared to normal.

9. The method according to claim 6, wherein the subject has at least a 10% loss in villous height in the small intestine, when compared to normal.

10. The method according to claim 6, wherein the composition does not comprise one or more ingredients selected from glucose, glutamine, and methionine, or, if one or more of these ingredients is present, glucose is present at a concentration of less than 1 g/l, glutamine is present at a concentration of less than 300 mg/l, and methionine is present at a concentration of less than 300 mg/l.

11. The method according to claim 6, wherein the composition further comprises aspartic acid, isoleucine, tryptophan, asparagine, and/or serine.

12. The method according to claim 6, wherein the composition does not comprise one or more ingredients selected from glucose, glutamine, or methionine.

13. The method according to claim 5, wherein the villous atrophy is caused by disease, radiation, chemotherapy, proton therapy, abdominal surgery, and/or a cytotoxic agent.

14. The method according to claim 13, wherein the composition is administered for a period of 1 to 14 days after the subject receives radiation, chemotherapy, proton therapy, or a cytotoxic agent.

15. The method according to claim 13, used to treat radiation enteritis.

16. The method according to claim 13, used to treat small intestine injury caused by chemotherapy or cytotoxic agents selected from cisplatin, 5-fluorouracil (5-FU), hydroxyurea, etoposide, arabinoside, 6-mercaptopurine, 6-thioguanine, fludarabine, methothexate, steroids, or a combination thereof.

17. The method according to claim 13, used to treat inflammatory bowel disease (IBD), ulcerative colitis, duodenal ulcers, or Crohn'"'"'s diseases.

22. A package containing the composition of claim 1, or powder which, when combined with water, makes a composition of claim 1, wherein said package further comprises instructions for administering the composition to a patient who has, or who is expected to develop, villous atrophy.

18. A method for preparing a sterile therapeutic composition for promoting intestinal health of a subject having villous atrophy, wherein said method comprises combining one or more ingredients selected from free amino acids, dipeptides, monosaccharides, disaccharides, or a combination thereof,

wherein each ingredient has been determined to retain at least 50% absorptive capacity in the small intestine of a subject with villous atrophy, when compared to normal, and

wherein the composition does not comprise glucose at a concentration of higher than 1 g/l or glutamine at a concentration of higher than 300 mg/l.

19. A composition produced by the method of claim 18.

20. The composition, according to claim 19, comprising water and having an osmolarity between 230 mosm and 280 mosm.

21. The composition, according to claim 19, in powder form.