BACTERIAL COMPOSITIONS FOR PROPHYLAXIS AND TREATMENT OF DEGENERATIVE DISEASE

• US 20110217368A1
• Filed: 05/19/2011
• Published: 09/08/2011
• Est. Priority Date: 05/01/2009
• Status: Active Grant

• Current Assignee: CHR Hansen Holding A/S
• Original Assignee: UAS Laboratories LLC (CHR Hansen Holding A/S)
• Inventors: Martoni, Christopher, Prakash, Satya, Jones, Mitchell Lawrence
• Granted Patent: US 10,660,857 B2
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A23C 2220/204 Use of bacteria which are encapsulated, entrapped or immobilised; Fermentation with these bacteria
• CPC Class Codes: A23C 9/1234 characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/224 Encapsulating agent
• CPC Class Codes: A23V 2200/3204 Probiotics, living bacteria to be ingested for action in the digestive tract
• CPC Class Codes: A23V 2200/3262 having an effect on blood cholesterol
• CPC Class Codes: A23V 2400/173 Reuteri
• CPC Class Codes: A61K 35/744 Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12N 1/20 : Bacteria; Culture media therefor
• CPC Class Codes: C12N 1/205 : Bacterial isolates
• CPC Class Codes: C12N 11/10 : the carrier being a carbohydrate
• CPC Class Codes: C12R 2001/225 : Lactobacillus
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The disclosure provides an oral composition for reducing serum cholesterol, serum lipids, body fat, or atherogenic index or for prophylaxis or treatment of atherosclerosis, cardiovascular or cerebrovascular diseases, comprising a highly bsh active bacteria, isolate or supernatant thereof; wherein the highly bsh active bacteria degrades >50 μmol glycodeoxycholic acid (GDCA)/gram/hour and >2 μmol taurodeoxycholic acid (TDCA)/gram/hour when measured over 1 hour and 5 hours, respectively, or degrades >65 μmol GDCA/g/hr and >7 μmol TDCA/g/hr when measured over 30 minutes.

Claims

1. An oral composition comprising a highly bsh active bacteria, isolate or supernatant thereof;

wherein the highly bsh active bacteria degrades >

50 μ

mol GDCA/gram/hour and >

2 μ

mol TDCA/gram/hour when measured over 1 hour and 5 hours, respectively;

or >

65 μ

mol GDCA/g/hr and >

7 μ

mol TDCA/g/hr when measured over 30 minutes.

2. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >

300 μ

mol GDCA/g/hr and >

40 μ

mol TDCA/g/hr when measured over 30 minutes.

3. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >

2000 μ

mol GDCA/g/hr and >

500 μ

mol TDCA/g/hr when measured over 30 minutes.

4. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >

15000 μ

mol GDCA/g/hr and >

2000 μ

mol TDCA/g/hr when measured over 30 minutes.

5. The oral composition of claim 1, wherein the bacteria is Lactobacillus, Bifidobacteria, Pediococcus, Streptococcus, Enterococcus, or Leuconostoc.

6. The oral composition of claim 5, wherein the Lactobacillus reuteri is Lactobacillus reuteri (NCIMB 701359), Lactobacillus reuteri (NCIMB 701089), Lactobacillus reuteri (ATCC 55148), Lactobacillus reuteri (ATCC 23272), Lactobacillus reuteri (NCIMB 702655), Lactobacillus reuteri (LMG 18238), Lactobacillus reuteri (CCUG 32271), Lactobacillus reuteri (CCUG 32305), Lactobacillus reuteri (CCUG 37470), Lactobacillus reuteri (CCUG 44001) or Lactobacillus reuteri (CCUG 44144).

7. The oral composition of claim 1, wherein the concentration of bacteria is 10⁶-10¹² CFU/gram.

8. The oral composition of claim 1, wherein the highly bsh active bacteria are grown under fermentation conditions comprising a carbon source, a nitrogen source, a pH of 4-7 and a harvest time of 6 to 24 hours.

9. The oral composition of claim 8, further comprising a reducing agent.

10. The oral composition of claim 1, wherein the bacteria are immobilized in a polymer or are encapsulated in polymeric semi permeable microcapsules or nanocapsules.

11. The oral composition of claim 1, wherein the composition is lyophilized, heat dried, spray dried, prepared wet, or flash frozen in a cryoprotectant solution.

12. The oral composition of claim 11, wherein the composition is lyophilized with lyoprotectants comprising (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine.

13. The oral composition of claim 11, wherein the composition is stored in liquid, wherein the liquid storage conditions comprise a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution.

14. The oral composition of claim 11, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05% to 10% inulin and 0.01 to 0.1% cysteine.

15. The oral composition of claim 1, wherein the composition further comprises a triglyceride lowering agent, an agent for increasing HDL or limiting HDL decrease, a cholesterol lowering agent, an agent for preserving bsh activity, an agent for modulating adipokines or hormones of obesity, a hypoglycemic agent, a therapeutic for reducing the pro-inflammatory cytokines IL-1α

/β

, IL-2, IL-15, IL-3, IL-6, IL-8, IL-12, IL-17, IFN-gamma, TNF-alpha, or for increasing the level of the anti-inflammatory cytokines IL-1ra, IL-9, IL-10, IL-11, vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin.

16. A method for lowering serum cholesterol of an animal comprising administering the oral composition of claim 1 to the animal in need thereof.

17. The method of claim 16, for reducing atherosclerotic risk factors of the animal, wherein the atherosclerotic risk factors are selected from serum homocystine, fibrinogen, C-reactive protein, lipoprotein(a), uric acid, matrix metallopeptidase 9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1) or its antigen, tissue plasminogen activator (tPA), TNF alpha, IL-6, P-selectin, monocyte chemotactic protein-1 (MCP-1), soluble CD40 ligand (sCD40L), inter-cellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), adiponectin, leptin, lipoprotein-associated phospholipase A, and insulin.

18. A method for reducing the atherogenic index of an animal comprising administering the oral composition of claim 1 to the animal in need thereof, wherein atherogenic index (AI) is calculated by at least one of the following equations:

AI=Log(Triglycerides/HDL-C) or AI=TC-HDL-C/HDL-C.

19. A method for increasing or limiting the reduction of serum high density lipoproteins (HDL-C) of an animal, for decreasing serum triglycerides of the animal, or for producing and delivering vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin to the animal, comprising administering the oral composition of claim 1 to the animal in need thereof.

20. A method for prophylaxis or treatment of atherosclerosis or a degenerative disorder caused by atherosclerosis in an animal, for lowering total body fat or treating obesity or pre-obesity in an animal, for prophylaxis or treatment of metabolic disease or disorder in an animal or for prophylaxis or treatment of a liver disease or disorder associated with high serum or hepatic lipid and triglyceride concentrations, hepatic inflammation, non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, liver steatosis, liver fibrosis, abnormally high serum ALT, AST, GGT, or Alk-P levels, Epstein-Barr virus, hepatitis, autoimmune hepatitis, hepatic granulomatus disease, cholangitis, hepatocellular cancer, cholangiocarcinoma or metabolic liver disease in an animal, comprising administering the oral composition of claim 1 to the animal in need thereof.

21. A process for preparing a highly bsh active bacteria comprising growing bsh-producing bacteria in media comprising a carbon source, a nitrogen source, and a pH of 4 to 7 and harvesting the bacteria after 6 to 24 hours.

22. The process of claim 21, wherein the media further comprises a reducing agent

23. The process of claim 21, further comprising lyophilizing the free or microencapsulated bacteria with lyoprotectants, wherein the lyoprotectants comprise (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine.

24. The process of claim 21, further comprising storing the highly bsh active free or microencapsulated bacteria under liquid storage conditions, wherein the liquid storage conditions comprises a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution.

25. The process of claim 21, further comprising flash freezing the composition in cryoprotectant solution at less than −

80 Degrees Celsius, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05 to 10% inulin and 0.01 to 0.1% cysteine.