Control of acidic gut syndrome

• US 6,468,964 B1
• Filed: 07/25/2001
• Issued: 10/22/2002
• Est. Priority Date: 06/27/1997
• Status: Expired due to Fees

• Current Assignee: James Baber, Prof Rowe
• Original Assignee: University of New England of Armidale
• Inventors: Rowe, James Baber
• Primary Examiner(s): Weddington, Kevin E.
• Application Number:
  US09/912,886
• Time in Patent Office: 454 Days
• Field of Search: 514/6, 514/8, 514/9, 514/31, 514/37, 514/54, 514/152, 514/200, 514/311, 514/770, 514/926
• US Class Current: 424/94.61
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

According to the present invention there is provided a method for the treatment or prophylaxis of acidic gut syndrome resulting from the accumulation of acid and production of endotoxin in the gastrointestinal tract of a human or an animal, said accumulation resulting from the fermentation of carbohydrate in the gastrointestinal tract of said human or animal, wherein said method comprises administering to said human or animal an effective amount of an active agent capable of preventing or controlling acid and endotoxin accumulation in the gastrointestinal tract.

Claims

1. A method for the treatment or prophylaxis of acidic gut syndrome resulting from the accumulation of acid and production of endotoxin in the gastrointestinal tract of a human or an animal, said accumulation resulting from the fermentation of carbohydrate in the gastrointestinal tract of said human or animal, wherein said method comprises administering to said human or animal an effective amount of an active agent capable of preventing or controlling acid and endotoxin accumulation in the gastrointestinal tract.

2. The method of claim 1, wherein said active agent is selected from the group consisting of:

antibiotics, enzyme preparations, clay preparations, compounds which slow the rate at which gut contents passes through the digestive tract, and probiotic preparations.

3. The method of claim 1, wherein said active agent is an antibiotic active against lactic acid producing gram-positive bacteria.

4. The method of claim 1, wherein said antibiotic is selected from the group consisting of a glycopeptide antibiotic, a glycolipid antibiotic, a staphylamycin antibiotic, a polypeptide antibiotic, a macrolide antibiotic, a sulphur-containing peptide antibiotic, a lincosamide antibiotic, tiamulin, a nitrofuran antibiotic, a tetracycline antibiotic, a penicillin antibiotic, a polythiazole antibiotic, an ionophore antibiotic, a cephalosporin antibiotic, a sulphonamide antibiotic, an aminoglycoside antibiotic, a quinalone antibiotic, streptogramin antibiotic, and any other antibiotic active against gram-positive bacteria responsible for the production of acid in the gastrointestinal tract.

5. The method of claim 4, wherein said antibiotic is selected from the group consisiting of:

glycopeptide antibiotics, glycolipid antibiotics, staphylomycin antibiotics, polypeptide antibiotics, macrolide antibiotics, sulfur-containing peptide antibiotics, lincosamide antibiotics, nitrofuran antibiotics, tetracycline antibiotics, penicillin antibiotics, polythiazole antibiotics, ionophore antibiotics, streptogramin antibiotics, streptogramin combinations, everninomycin derivatives, oxazolidinones, fluoroquinolone antibiotics, beta-lactam antibiotics, margainin antibiotics, chloramphenicols and related compounds, and any combination thereof.

6. The method of claim 1, wherein said active agent is an exogenous enzyme preparation designed to reduce the passage of fermentable carbohydrate to the hind gut.

7. The method of claim 6, wherein said exogenous enzyme preparation comprises one or more of:

glyconases, glucanases, enzymes which break down galactosides of the raffinose series and other galactosides, enzymes which break down the proteins forming part of the matrix surrounding starches, sugars and non-starch carbohydrates in plant material, natural and synthetic proteolytic enzymes of chemical or microbial origin, enzymes which depolymerise non-starch polysaccharides, enzymes active in the break down of cellulose, enzymes active in the break down of colloidal polysaccharides, pectic substances, neutral polysaccharides, and other non-starch polysaccharides.

8. The method of claim 1, wherein said active agent is a clay preparation which reduces the rate of fermentation and binds specific ions in a way which reduces the adverse effects of rapid fermentation of starch and other soluble carbohydrates in the gastrointestinal tract.

9. The method of claim 8, wherein said clay preparation comprises:

kaolinite, bentonite, montmorrilonite, illite, clinoliptolite, heulandite, palygorsite, saponite, smectite, chrysotile, lizardite, talc, pyrophyllite, vermiculite, beidellite, halloysite and zeolite types of clay, or a mixture of two or more thereof.

10. The method of claim 1, wherein said active agent is a compound which reduces the rate at which material moves through the digestive tract, thereby increasing intestinal digestion and absorption and reducing the amount of fermentable substrate passing to the hind gut.

11. The method of claim 10, wherein said compound which reduces the rate at which material moves through the digestive tract is selected from the group consisting of:

biologically active peptides (BAP), opioid peptides, β

-casomorphins, cholecystokinin (CCK), the M1 fraction of virginiamycin and the analogue of virginiamycin fraction M1, compound L-156.

12. The method of claim 1, wherein said active agent is a probiotic preparation which reduces lactic acid accumulation by formation of alternative end products of fermentation;

production of volatile fatty acids rather than lactic acid during carbohydrate fermentation, through increased utilization of lactic acid, or through the conversion of lactic acid to volatile fatty acids which can be absorbed from the gut, thereby reducing acidity in the gut.

13. The method of claim 12, wherein said probiotic preparation comprises bacteria.

14. The method of claim 13, wherein said bacteria is selected from the group consisting of:

Succinomonas, Butyrivibrio, Bacteroides, Succinivibrio, Megasphera, Veillenolla, Selenomonas, Propionibacterium, Anaerovibrio and Peptococcus.

15. The method of claim 12, wherein said probiotic preparation comprises yeast and/or mycelial preparations capable of utilizing lactic acid.

16. The method of claim 1, wherein said active agent is administered to said human or animal subjects via targeted delivery to the hind gut of said human or animal subjects, using enteric coated delivery systems to ensure specific activity of said active agent in the terminal ileum, colon and/or caecum of said human or animal subjects.

17. The method of claim 6, wherein said exogenous enzyme preparation is selected from the group consisting of:

amylase, maltase, invertase, α

-glucosidases, emulsin, amyloglucosidase, β

-glucanase, xylanase, α

-galactosidase, pepsin, trypsin, trypsinogen, chymotrypsin, and cellulase.

18. The method of claim 4, wherein said antibiotic is selected from the group consisiting of:

avoparcin, teicoplanin, vancomycin, flavomycin (bambermycin), virginiamycin, bacitracin zinc, bacitracin methylene disalicylate, virginiamycin S, polymixins (B &

E), tylosin, spiramycin, virginiamycin M, josamycin, spectinomycin, erthromycin, thiopeptone, thiopeptin, sulfomycin, thiostrepton, sporangiomycin, siomycin, taitomycin, lincomycin, clindamycin, tiamulin, nitrofurantoin, nitrofurazone, furazolidone, chlortetracycline, oxytetracycline, oxacillin, methicillin, penicillin V, ampicillin, nosiheptide, lasalocid, tetronasin, naracin, solinomycin, ardacin, novobiocin sodium, bottromycin tartrate, quinupristin/dalfoprisitin, streptogramin combinations, everninomycin derivatives, oxazolidinones, ciprofloxacin, ofloxacin, clinafloxacin, DU 6859a, grepafloxacin, levofloxacin, sparfloxacin, trovafloxacin, nitrovin (payzone), enramycin, mupiricin, chloramphenicol, florphenicol, and any combination thereof.