Bacterial compositions for prophylaxis and treatment of degenerative disease

• US 10,660,857 B2
• Filed: 05/19/2011
• Issued: 05/26/2020
• 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: Prakash, Satya, Jones, Mitchell Lawrence, Martoni, Christopher
• Primary Examiner(s): Afremova, Vera
• Application Number:
  US13/111,105
• Publication Number:
  US 20110217368A1
• Time in Patent Office: 3,295 Days
• Field of Search: None
• 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. A bile salt hydrolase (BSH) active bacteria, comprising a first BSH activity that results from growth in an optimized plurality of growth medium components, wherein said first BSH activity is between 6.1 and 113.6 fold higher than a second BSH activity that results from the growth of said BSH active bacteria in de Man, Rogosa, Sharpe (MRS) medium.

2. The BSH active bacteria of claim 1, wherein said first BSH activity is between 8.9 and 113.6 fold higher than said second BSH activity.

3. The BSH active bacteria of claim 2, wherein said first BSH activity is between 39.7 and 113.6 fold higher than said second BSH activity.

4. The highly BSH active bacteria of claim 3, wherein said first BSH activity is between 84.8 and 113.6 fold higher than said second BSH activity.

5. An oral composition, comprising the BSH active bacteria of claim 2;

wherein said first BSH activity degrades >

2253 μ

mol glycodeoxycholic acid (GDCA)/gram wet bacterial pellet/hr when measured over 30 minutes, wherein said high BSH activity is stable so that at least about 69.2% of said BSH activity is retained when said highly BSH active bacteria are stored for a time period of at least 3 weeks.

6. The oral composition of claim 5, wherein said first BSH activity degrades >

15000 μ

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

7. The BSH active bacteria of claim 1, wherein the BSH active bacteria is Lactobacillus, Bifidobacteria, Pediococcus, Streptococcus, Enterococcus, or Leuconostoc.

8. The BSH active bacteria of claim 7, wherein the bacteria is Lactobacillus.

9. The BSH active bacteria of claim 8, wherein the Lactobacillus is Lactobacillus reuteri.

10. The BSH active bacteria of claim 9, 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).

11. The BSH active bacteria of claim 10, wherein the Lactobacillus reuteri is Lactobacillus reuteri (NCIMB 701359).

12. The oral composition of claim 6, wherein the bacteria is Lactobacillus.

13. The oral composition of claim 12, wherein the Lactobacillus is Lactobacillus reuteri.

14. The oral composition of claim 13, wherein the Lactobacillus reuteri is Lactobacillus reuteri (NCIMB 701359).

15. The BSH active bacteria of claim 1, wherein said optimized plurality of growth medium components comprises:

a. a carbon source comprising maltose or a combination of inulin and glucose; and

b. a nitrogen source comprising yeast extract, malt extract, and peptone No. 3;

wherein said growth medium components are in a growth medium having a pH of 5-7.

16. The BSH active bacteria of claim 15, wherein the optimized plurality of growth medium components further comprises a reducing agent.

17. The oral composition of claim 16, wherein the reducing agent is cysteine.

18. The BSH active bacteria of claim 1, wherein the bacteria are immobilized in a polymer or are encapsulated in polymeric semi permeable microcapsules or nanocapsules.

19. The oral composition of claim 3, wherein said first BSH activity has been stabilized by lyophilizing, heat drying, spray drying, or flash freezing said BSH active bacteria following said growth in said plurality of growth medium components.

20. The oral composition of claim 19, wherein said BSH active bacteria are 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) 1M Trehalose, or (e) 1M trehalose and 0.33% yeast extract.

21. The oral composition of claim 3, wherein said first BSH activity has been stabilized by flash freezing said BSH active bacteria in a cryoprotectant solution comprising a final concentration of (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose, (e) 0.5M lactose, (f) 0.5M maltose, or (g) 50-99.99% spent media.

22. The oral composition of claim 5, wherein the oral 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-la/B, 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.