Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use

• US 5,716,615 A
• Filed: 05/24/1995
• Issued: 02/10/1998
• Est. Priority Date: 02/10/1992
• Status: Expired

• Current Assignee: Claudio D.E. Simone, Renata Maria Anna Cavaliere Vesely
• Original Assignee: Claudio D.E. Simone, Renata Maria Anna Cavaliere Vesely
• Inventors: De Simone, Claudio, Cavaliere Vesely, Renata Maria Anna
• Primary Examiner(s): Naff, David M.
• Assistant Examiner(s): Ware, Deborah K.
• Application Number:
  US08/448,787
• Time in Patent Office: 993 Days
• Field of Search: 424/93.44, 424/93.45, 424/93.4, 426/61, 435/252.4, 435/260, 435/856, 435/885, 435/252.9, 435/253.4
• US Class Current: 424/93.4
• CPC Class Codes: A23L 29/065 Microorganisms addition of bacteria for nutritional purposes A23L33/135
• CPC Class Codes: A23V 2400/169 Plantarum
• CPC Class Codes: A23V 2400/249 Thermophilus
• CPC Class Codes: A23V 2400/51 Bifidobacterium
• 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 35/744 Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• CPC Class Codes: A61K 35/745 Bifidobacteria
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A pharmaceutical composition containing several different bacteria including Streptococcus thermophilus, Lactobacilli and Bifidobacteria is disclosed. The bacteria are present in the composition at a total concentration of 1×10¹¹ to 1×10¹³ per gram. Further, methods of using the pharmaceutical are disclosed which include treatment of a gastrointestinal disorder and hypercholesteremia. Also a method for modulating a host'"'"'s immune response is disclosed.

Claims

1. A pharmaceutical composition comprising:

a) from 10% to 95% by weight of total composition of lyophilized Streptococcus thermophilus, and

b) from 5% to 90% by weight of total composition of at least one lyophilized bacterium selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei, and

c) from 0% to 10% by weight of total composition a pharmaceutically acceptable excipient,

wherein said Streptococcus thermophilus and the bacterium b) are present in a concentration of 1×

10¹¹ -1×

10¹³ total bacteria per gram of the composition.

2. The pharmaceutical composition of claim 1 which further contains an excipient in an amount of 1 to 10% by weight based on total composition.

3. The pharmaceutical composition of claim 2, wherein said excipient is selected from the group consisting of maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose and dextrose.

4. The pharmaceutical composition of claim 1 which further contains from 85% to 5% by weight of one or more lyophilized bacteria selected from the group consisting of bifidobacteria, Lactobacillus acidophilus, Lactobacillus delbrueckii sub-species bulgaricus and Streptococcus faecium, wherein the concentration of this bacterium is from 1×

10⁹ to 1×

10¹² bacteria per gram of the composition.

5. The pharmaceutical composition of claim 4, wherein said bifidobacteria is a mixture of Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium infantis is approximately in equal weight distribution.

6. The pharmaceutical composition of claim 1, which further comprises from 1 to 20% by weight of total composition of a drug which is compatible with the bacteria in said composition.

7. The pharmaceutical composition of claim 6, wherein said drug is selected from the group consisting of anticholinergics, antihistamines, analgesics, adrenergics, antiinflammatories, antiseptics, hepatoprotective agents and antilipemics.

8. The pharmaceutical composition according to claim 1, which contains 1 to 10% by weight of total composition of said pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising:

(a) from 30-35% by weight of lyophilized Streptococcus thermophilus;

(b) from 7-10% by weight of lyophilized Lactobacillus casei;

(c) from 8-10% by weight of lyophilized Lactobacillus plantarum;

(d) from 7-10% by weight of lyophilized Lactobacillus acidophilus;

(e) from 8-10% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus;

(f) from 27-30% by weight of a mixture of lyophilized bifidobacteria; and

(g) from 8-10% by weight of a pharmaceutically acceptable excipient,

wherein all amounts are based on the total weight of the composition and said bifidobacteria is a mixture of Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium bifidum;

wherein said excipient is selected from the group consisting of maltodextrin, levulose, microcrystalline cellulose, maize starch, lactose, and dextrose; and

wherein said Streptococcus thermophilus, said Lactobacillus casei, and said Lactobacillus plantarum are present in said pharmaceutical composition in a total concentration of 1×

10¹¹ to 1×

10¹³ bacteria per gram.

10. The pharmaceutical composition of claim 9, wherein said bifidiobacteria is a mixture 1:

1;

1 by weight.

11. A method for treating hypercholesteremia, comprising administering to a patient in need thereof an effective amount of a composition, said composition comprising:

(a) from 10 to 95% by weight of total composition of lyophilized Streptococcus thermophilus;

(b) from 5 to 90% by weight of total composition of at least one lyophilized bacteria selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei; and

(c) from 0 to 10% by weight of total composition of a pharmaceutically acceptable excipient;

wherein said Streptococcus thermophilus, Lactobacillus plantarum, and Lactobacillus casei are present in such amounts that the total bacteria concentration in said composition is 1×

10¹¹ to 1×

10¹³ total bacteria per gram of composition.

12. The method of claim 11, wherein said composition comprises 1 to 10% by weight of said excipient.

13. The method of claim 12, wherein said excipient is selected from the group consisting of maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose, and dextrose.

14. The method of claim 11, wherein said composition further comprises from 85% to 5% by weight of one or more lyophilized bacteria selected from the group consisting of bifidobacteria, Lactobacillus acidophilus, Lactobacillus delbrueckii sub-species bulgaricus and Streptococcus faecium, in a concentration of from 1×

10⁹ to 1×

10¹² bacteria per gram of said composition.

15. The method of claim 14, wherein said bifidobacteria is a mixture of Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium infantis in approximately an equal weight distribution.

16. The method of claim 11, wherein said composition comprises:

(a) from 30-35% by weight of lyophilized Streptococcus thermophilus;

(b) from 7-10% by weight of lyophilized Lactobacillus casei;

(c) from 8-10% by weight of lyophilized Lactobacillus plantarum;

(d) from 7-10% by weight of lyophilized Lactobacillus acidophilus;

(e) from 8-10% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus;

(f) from 27-30% by weight of lyophilized bifidobacteria; and

(g) from 8-10% by weight of an excipient, wherein all amounts are based on the total weight of said composition and said bifidobacteria is a mixture 1;

1;

1 by weight of Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium bifidum, and said excipient is selected from the group consisting of maltodextrin, levulose, microcrystalline cellulose, maize starch, lactose, and dextrose.

17. The method of claim 11, wherein said administering is oral administration.

18. A method for treating a gastrointestinal disorder, comprising administering to a patient in need thereof an effective amount of a composition, said composition comprising:

(a) from 10 to 95% by weight of total composition of lyophilized Streptococcus thermophilus;

(b) from 5 to 90% by weight of total composition of at least one lyophilized bacteria selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei; and

(c) from 0 to 10% by weight of total composition of a pharmaceutically acceptable excipient;

wherein said Streptococcus thermophilus, Lactobacillus plantarum, and Lactobacillus casei are present in such amounts that the total bacteria concentration in said composition is 1×

10¹¹ to 1×

10¹³ total bacteria per gram of composition.

19. The method of claim 18, wherein said composition comprises 1 to 10% by weight of said excipient.

20. The method of claim 19, wherein said excipient is selected from the group consisting of maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose, and dextrose.

21. The method of claim 18, wherein said composition further comprises from 85% to 5% by weight of one or more lyophilized bacteria selected from the group consisting of bifidobacteria, Lactobacillus acidophilus, Lactobacillus delbrueckii sub-species bulgaricus, and Streptococcus faecium, in a concentration of from 1×

10⁹ to 1×

10¹² bacteria per gram of said composition.

22. The method of claim 21, wherein said bifidobacteria is a mixture of Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium infantis in approximately an equal weight distribution.

23. The method of claim 18, wherein said composition comprises:

(a) from 30-35% by weight of lyophilized Streptococcus thermophilus;

(b) from 7-10% by weight of lyophilized Lactobacillus casei;

(c) from 8-10% by weight of lyophilized Lactobacillus plantarum;

(d) from 7-10% by weight of lyophilized Lactobacillus acidophilus;

(e) from 8-10% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus;

(f) from 27-30% by weight of lyophilized bifidobacteria; and

(g) from 8-10% by weight of an excipient, wherein all amounts are based on the total weight of said composition and said bifidobacteria is a mixture 1;

1;

1 by weight of Bifidobacterium longum, Bifidobacterium infantis and Bifidobacterium bifidum, and said excipient is selected from the group consisting of maltodextrin, levulose, microcrystalline cellulose, maize starch, lactose, and dextrose.

24. The method of claim 18, wherein said administering is oral administration.

25. The method of claim 18, wherein said gastrointestinal disorder is diarrhea.

26. The method of claim 18, wherein said gastrointestinal disorder is irritable bowel syndrome.

27. A method for modulating a host'"'"'s immune response, comprising administering to a patient in need thereof an effective amount of a composition, said composition comprising:

(a) from 10 to 95% by weight of total composition of lyophilized Streptococcus thermophilus;

(b) from 5 to 90% by weight of total composition of at least one lyophilized bacteria selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei; and

(c) from 0 to 10% by weight of total composition of a pharmaceutically acceptable excipient;

wherein said Streptococcus thermophilus, Lactobacillus plantarum, and Lactobacillus casei are present in such amounts that the total bacteria concentration in said composition is 1×

10¹¹ to 1×

10¹³ total bacteria per gram of composition.

28. The method of claim 27, wherein said composition comprises 1 to 10% by weight of said excipient.

29. The method of claim 28, wherein said excipient is selected from the group consisting of maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose, and dextrose.

30. The method of claim 27, wherein said composition further comprises from 85% to 5% by weight of one or more lyophilized bacteria selected from the group consisting of bifidobacteria, Lactobacillus acidophilus, Lactobacillus delbrueckii sub-species bulgaricus, and Streptococcus faecium, in a concentration of from 1×

10⁹ to 1×

10¹² bacteria per gram of said composition.

31. The method of claim 30, wherein said bifidobacteria is a mixture of Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium infantis in approximately an equal weight distribution.

32. The method of claim 27, wherein said composition comprises:

(a) from 30-35% by weight of lyophilized Streptococcus thermophilus;

(b) from 7-10% by weight of lyophilized Lactobacillus casei;

(c) from 8-10% by weight of lyophilized Lactobacillus plantarum;

(d) from 7-10% by weight of lyophilized Lactobacillus acidophilus;

(e) from 8-10% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus;

(f) from 27-30% by weight of lyophilized bifidobacteria; and

(g) from 8-10% by weight of an excipient, wherein all amounts are based on the total weight of said composition and said bifidobacteria is a mixture 1;

1;

1 by weight of Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium bifidum, and said excipient is selected from the group consisting of maltodextrin, levulose, microcrystalline cellulose, maize starch, lactose, and dextrose.

33. The method of claim 27, wherein said administering is oral administration.