USRE40023E1 - Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use - Google Patents

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

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USRE40023E1
USRE40023E1 US11/375,704 US37570406A USRE40023E US RE40023 E1 USRE40023 E1 US RE40023E1 US 37570406 A US37570406 A US 37570406A US RE40023 E USRE40023 E US RE40023E
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lyophilized
lactobacillus
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Claudio DeSimone
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/065—Microorganisms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/169—Plantarum
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/21—Streptococcus, lactococcus
    • A23V2400/249—Thermophilus
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium

Definitions

  • the present invention relates to dietary and pharmaceutical compositions useful for dietary or certain pharmaceutical indications, said composition containing lyophilized, lactic bacteria. Said compositions, being useful for prophylaxis or treatment of gastrointestinal disorders, or for treatment of hypocholesterolemia.
  • Takano et al. U.S. Pat. No. 4,913,913, describes a method for preparing a bifidobacteria-containing fermented milk, in which Lactobacilius casei and Bifidobacterium longum are cultivated in admixture or are mixed after being separately cultivated, and thus a bifidobacteria-containing lactic acid bacteria-fermented milk with an elevated survival rate of Bifidobacterium longum is obtained.
  • composition comprising at least two lactic acid bacteria strains allows improved therapeutical results to be achieved of a kind never previously attained by prior art compositions, provided that the concentration of each of two lactic bacteria strains exceeds 10 11 viable lactic bacteria/gram of composition.
  • composition of the present invention can be used in combination with any of a variety of compatible drugs.
  • the present composition can be used to antagonize the onset of diarrhea, constipation, hypercholesteremia, endotoxin absorption or production of endogenous toxic substances.
  • compositions of the present invention comprise as essential active ingredients: (a) from 10 to 95% by weight of total composition of lyophilized lactic bacterium Streptococcus thermophilus, and (b) from 90 to 5% by weight of total composition of at least one further lyophilized lactic bacterium selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei.
  • An excipient in an amount of from 1 to 10% by weight of total components can be added, said amounts being all based on the total weight of the composition.
  • the composition can be used in combination with a compatible pharmaceutical in an amount of from 1 to 20% by weight based on the total weight of the composition.
  • the viable bacteria concentration be at least 1 ⁇ 10 11 for (a) and 1 ⁇ 10 11 for (b) per gram of the composition.
  • the viable bacteria concentration of both (a) and (b) should be used between 1 ⁇ 10 11 and 1 ⁇ 10 13 per gram of the composition.
  • compositions of the invention can be prepared with methods well-known to those skilled in dairy technology, enabling the presence of viable bacteria at concentrations ranging between 1 ⁇ 10 11 and 1 ⁇ 10 13 bacteria per gram of the composition.
  • the composition should also contain from 85 to 5% by weight of one or more lyophilized lactic bacteria selected from bifidobacteria (preferably a mixture of lyophilized Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium infantis, ratio of 1:1:1 by weight) at a concentration ranging between 1 ⁇ 10 9 and 1 ⁇ 10 12 viable bacteria per gram of the composition, lyophilized Lactobacillus acidophilus at a concentration of from 1 ⁇ 10 9 to 1 ⁇ 10 12 viable bacteria per gram of the composition, lyophilized lactobacillus delbruekii sub-species bulgaricus at a concentration of from 1 ⁇ 10 9 to 1 ⁇ 10 12 viable bacteria per gram of the composition, and lyophilized Streptococcus faecium at a concentration of from 1 ⁇ 10 9 to 1 ⁇ 10 12 bacteria per gram of the composition, optionally with 1 to 10% of an excipient and 1 to
  • a particularly preferred composition according to the present invention contains: a) 31% by weight of lyophilized Streptococcus thermophilus, 7 ⁇ 10 11 ; b) 7% by weight of lyophilized Lactobacillus casei, 1 ⁇ 10 11 ; c) 8% by weight of lyophilized Lactobacillus plantarum, 1 ⁇ 10 11 ; d) 7% by weight of lyophilized Lactobacillus acidophilus, 2 ⁇ 10 10 ; e) 8% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus, 3 ⁇ 10 9 ; f) 27% by weight of lyophilized bifidobacteria, 38 ⁇ 10 10 ; and g) 12% by weight of an excipient, wherein all the amounts are based on the total weight of the composition and Bifidobacterium Bifidum, Bifidobacterium longum and Bifidobacterium infantis.
  • compositions of the invention may contain usual excipients as are conventionally used for preparing pharmaceutical compositions in which normally the ratio of the active ingredient to the excipient will range between 1:10 and 99:90.
  • compositions of the invention can be made in conventional pharmaceutical forms, such as for example tablets, coated tablets, capsules, packets, solutions, sachets, suspensions, emulsions, suppositories, pellets, syrups, vaginal suppositories, and are prepared in the usual m manner by mixing active ingredients in the mentioned amounts, eventually adding excipients and/or carriers, adjuvants and/or dispersing agents.
  • Water may be used as the diluent.
  • Organic solvents can be used in the form of adjuvants.
  • Adjuvants can be for example, non-toxic organic solvents such as paraffines, vegetable oils (peanut oil or sesame oil), glycerine, glycols (propylene glycol, polyethylene glycol), solid carriers such as for example natural mineral flours (kaolin, talc), synthetic mineral flours (silicates for example), sugar (cane sugar for example), emulsifiers (alkylsulfonates or arylsulfonates and the like), dispersants (lignin, methylcellulose, starch and polyvinylpyrrolidone, for example) and lubricants (magnesium stearate, talc, stearic acid, sodium laurylsolfonate, for example).
  • Preferred excipients for the composition of the invention are maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose and dextrose.
  • the administration takes place in the usual manner, preferably by oral route.
  • pharmaceutical forms adapted to this end can obtain, in addition to usual excipients, also additives such as sodium citrate, calcium carbonate, calcium dihydrogen phosphate, together with several additional substances such as starch, gelatin and the like.
  • additional substances such as starch, gelatin and the like.
  • compatible colouring agents of flavoring substances may be added.
  • the compositions may contain such compatible pharmaceuticals as anticholinergies, antihistamines, analgesics, adrenergics, antiinflammatories, antiseptics, hepatoprotective agents, or antilipemic drugs, in amounts of from 1 to 20% by weight, based on the total weight of the composition.
  • compatible pharmaceuticals as anticholinergies, antihistamines, analgesics, adrenergics, antiinflammatories, antiseptics, hepatoprotective agents, or antilipemic drugs.
  • the formulation of the preparation was in form of sachets, each containing 3 g of the composition. All the following studies were carried out in human health volunteers and in patients enrolled after informed consent according to the Helsinki declaration. Medical and laboratory controls were done by physicians aware of the good usual clinical practice (GPC) as stated by the European Economic Community (EEC). Statistical analysis was carried out by a statistician, not directly involved in the study. T0, T1, T2, and T3 refer respectively to pre-treatment, after one, two and three weeks of treatment.
  • the individual strains maintained in a lyophilized and frozen form have been grown in synthetic media specific for each species.
  • the fundamental component of the culture medium is permeate obtained by ultrafiltration of serum or milk, to which minimal amounts of biological activators are added depending on the species. After sterilization, the culture medium is inoculated with a strain per species or 1 to 3 strains belonging to the same genotype. Cultures have been incubated upon determination of optimal parameters for each strain: temperature, time, pH values and stirring.
  • the mother has been prepared by inoculating the strain in a medium consisting of 5% of permeate +1% of yeast extract and incubated at 44° C. over 3 hours.
  • the mother has been prepared by inoculating the strains in a medium consisting of 10% of powdered skimmed milk +0.5% of glucose +1% of yeast extract and incubated at 38° C. over 15 hours.
  • Lyophilization Lyophilizer Edwards MINI - FAST 3400 Lyophilization protector a solution of powdered skimmed milk+yeast extract+lactose+sodium maleate has been prepared.
  • Lyophilization Lyophilizer Edwards MINI - FAST 3400 Lyophilization protector a solution of lactose and anhydrous mixture consisting of powdered skimmed milk+yeast extract+lactose+sodium maleate+Tween (Registered Trademark) 80. Results: the number of microorganisms during the different process steps is reproduced in the following Table:
  • Lactobacillus delbrueckii sub-species bulgaricus (ATCC 7994)
  • Lyophilization Lyophilizer Edwards MINI - FAST 3400 Lyophilization protector a solution of lactose and anhydrous mixture consisting of powdered skimmed milk+yeast extract+lactose+sodium glutamate+Tween (Registered Trademark) 80. Results: the number of micoorganisms during the different process steps is reproduced in the following Table:

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  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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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 hypercholestermia. Also a method for modulating a host's immune response is disclosed.

Description

This application is a reissue of application Ser. No. 08/448,787, filed May 24, 1995, now U.S. Pat. No. 5,716,615, which is a continuation of application Ser. No. 08/117,751, filed on Sep. 8, 1993, now abandoned, which is a continuation-in-part of application Ser. No. 07/983,839, filed Dec. 1, 1992, now abandoned.
FIELD OF THE INVENTION
The present invention relates to dietary and pharmaceutical compositions useful for dietary or certain pharmaceutical indications, said composition containing lyophilized, lactic bacteria. Said compositions, being useful for prophylaxis or treatment of gastrointestinal disorders, or for treatment of hypocholesterolemia.
BACKGROUND OF THE INVENTION
In Bifidobacteria Microflora, Vol. 3(1), 29-33, 1984, the beneficial effect of administering Bifidobacterium to patients suffering from leukemia is described. In FEMS Microbiology Reviews 46 (1987), 343-356, the therapeutical function of lactobacilli is disclosed, while Nobuo Suegara et al., Microecology and Therapy, Vol. 15, 271-280 (1985) state that oral administration of S. faecalis KAWAI greatly improves the lipid metabolism in human beings and animals. From Microecology and Therapy, Vol. 14, 109-126 (1984) the effect of streptococcus cell extracts on hyperlipemia in rats, rabbits and human beings is known. Other references describing the beneficial action of lactobacilli or other strains of activated lactobacilli are for example Bifidobacteria Microflora 1, 3-24, 1982 Recent Trends in Research on Intestinal Flora, Microecology and Therapy 14, 267, 1984 (Intestinal Flora Associated Endotoxin), Microecology Therapy 16, 271-272, 1986 (Bifidobacterium bifidum administration in Humans: a Controlled Clinical Study in Liver Cirrhosis), etc.
In Italian Patent No. 1,022,625 food and pharmaceutical compositions which stimulates the production of gamma-interferon and contain lactobacilli Streptococcus thermophilus and Lactobacillus bulgaricus are described.
In U.S. Pat. No. 4,806,368, Reddy envisaged the possibility of preparing dietary fiber based tablets with Lactobacillus acidophilus and/or Bifidobacterium bifidus, Leuconostoc citrovorum and Propionibacterium shermanii. To enhance the viability of L. acidophilus in the tablets, a combination of aminoacids, vitamins, calcium, magnesium salts, lactose and dietary fiber were included. The optimal concentration of lactobacilli in each 750 mg tablet was not higher than 1×107. High concentrations were avoided.
Fernandes et al. in their comprehensive review “Therapeutic role of dietary lactobacilli and lactobacillic fermented diary products,” published in FEMS Microbiology Reviews 46:343-356, 1987, indicate moreover the beneficial effects of lactobacilli, especially of L. acidophilus.
Takano et al., U.S. Pat. No. 4,913,913, describes a method for preparing a bifidobacteria-containing fermented milk, in which Lactobacilius casei and Bifidobacterium longum are cultivated in admixture or are mixed after being separately cultivated, and thus a bifidobacteria-containing lactic acid bacteria-fermented milk with an elevated survival rate of Bifidobacterium longum is obtained.
No suggestion is found in the literature to prepare a composition which combines several different lactic bacteria. In addition, there is no indication in the prior art to suggest administering to humans a concentration of lactobacilli exceeding 109 per gram.
SUMMARY OF THE INVENTION
It has now been found that a composition comprising at least two lactic acid bacteria strains allows improved therapeutical results to be achieved of a kind never previously attained by prior art compositions, provided that the concentration of each of two lactic bacteria strains exceeds 1011 viable lactic bacteria/gram of composition.
It is therefore an object of the present invention to provide an appropriate dietary and pharmaceutical composition comprising lyophilized lactic bacteria at high concentration per gram of product (>1011 bacteria/gram), qualitatively and quantitatively coordinated so as to be used for treatment or for prevention of certain gastrointestinal disorders, or for treatment or prevention of hypocholesterolemia or to potentiate the host's immune system. The composition of the present invention can be used in combination with any of a variety of compatible drugs.
The present composition can be used to antagonize the onset of diarrhea, constipation, hypercholesteremia, endotoxin absorption or production of endogenous toxic substances.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The compositions of the present invention comprise as essential active ingredients: (a) from 10 to 95% by weight of total composition of lyophilized lactic bacterium Streptococcus thermophilus, and (b) from 90 to 5% by weight of total composition of at least one further lyophilized lactic bacterium selected from the group consisting of Lactobacillus plantarum and Lactobacillus casei. An excipient in an amount of from 1 to 10% by weight of total components can be added, said amounts being all based on the total weight of the composition. The composition can be used in combination with a compatible pharmaceutical in an amount of from 1 to 20% by weight based on the total weight of the composition. It is essential that the viable bacteria concentration be at least 1×1011 for (a) and 1×1011 for (b) per gram of the composition. Preferably, the viable bacteria concentration of both (a) and (b) should be used between 1×1011 and 1×1013 per gram of the composition.
The compositions of the invention can be prepared with methods well-known to those skilled in dairy technology, enabling the presence of viable bacteria at concentrations ranging between 1×1011 and 1×1013 bacteria per gram of the composition.
According to a preferred embodiment, the composition should also contain from 85 to 5% by weight of one or more lyophilized lactic bacteria selected from bifidobacteria (preferably a mixture of lyophilized Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium infantis, ratio of 1:1:1 by weight) at a concentration ranging between 1×109 and 1×1012 viable bacteria per gram of the composition, lyophilized Lactobacillus acidophilus at a concentration of from 1×109 to 1×1012 viable bacteria per gram of the composition, lyophilized lactobacillus delbruekii sub-species bulgaricus at a concentration of from 1×109 to 1×1012 viable bacteria per gram of the composition, and lyophilized Streptococcus faecium at a concentration of from 1×109 to 1×1012 bacteria per gram of the composition, optionally with 1 to 10% of an excipient and 1 to 20% of a compatible pharmaceutical.
A particularly preferred composition according to the present invention contains: a) 31% by weight of lyophilized Streptococcus thermophilus, 7×1011; b) 7% by weight of lyophilized Lactobacillus casei, 1×1011; c) 8% by weight of lyophilized Lactobacillus plantarum, 1×1011; d) 7% by weight of lyophilized Lactobacillus acidophilus, 2×1010; e) 8% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus, 3×109; f) 27% by weight of lyophilized bifidobacteria, 38×1010; and g) 12% by weight of an excipient, wherein all the amounts are based on the total weight of the composition and Bifidobacterium Bifidum, Bifidobacterium longum and Bifidobacterium infantis.
As mentioned above, as further optional components the compositions of the invention may contain usual excipients as are conventionally used for preparing pharmaceutical compositions in which normally the ratio of the active ingredient to the excipient will range between 1:10 and 99:90.
The compositions of the invention can be made in conventional pharmaceutical forms, such as for example tablets, coated tablets, capsules, packets, solutions, sachets, suspensions, emulsions, suppositories, pellets, syrups, vaginal suppositories, and are prepared in the usual m manner by mixing active ingredients in the mentioned amounts, eventually adding excipients and/or carriers, adjuvants and/or dispersing agents. Water may be used as the diluent. Organic solvents can be used in the form of adjuvants. Adjuvants can be for example, non-toxic organic solvents such as paraffines, vegetable oils (peanut oil or sesame oil), glycerine, glycols (propylene glycol, polyethylene glycol), solid carriers such as for example natural mineral flours (kaolin, talc), synthetic mineral flours (silicates for example), sugar (cane sugar for example), emulsifiers (alkylsulfonates or arylsulfonates and the like), dispersants (lignin, methylcellulose, starch and polyvinylpyrrolidone, for example) and lubricants (magnesium stearate, talc, stearic acid, sodium laurylsolfonate, for example). Preferred excipients for the composition of the invention are maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose and dextrose.
The administration takes place in the usual manner, preferably by oral route. In this case pharmaceutical forms adapted to this end can obtain, in addition to usual excipients, also additives such as sodium citrate, calcium carbonate, calcium dihydrogen phosphate, together with several additional substances such as starch, gelatin and the like. In case of liquid compositions compatible colouring agents of flavoring substances may be added.
As an optional component, the compositions may contain such compatible pharmaceuticals as anticholinergies, antihistamines, analgesics, adrenergics, antiinflammatories, antiseptics, hepatoprotective agents, or antilipemic drugs, in amounts of from 1 to 20% by weight, based on the total weight of the composition. As mentioned above, for preparing the compositions, the individual microorganisms in the dehydrated form are mixed in appropriate proportions and the mixture is then admixed with the excipients or optionally with other pharmaceuticals.
PHARMACOLOGICAL STUDIES
The following studies were carried out using a composition of lyophilized viable Streptococcus thermophilus and Lactobacillus plantarum, at concentrations respectively of 6×1011 and 4×1011 per gram of the composition.
The formulation of the preparation was in form of sachets, each containing 3 g of the composition. All the following studies were carried out in human health volunteers and in patients enrolled after informed consent according to the Helsinki declaration. Medical and laboratory controls were done by physicians aware of the good usual clinical practice (GPC) as stated by the European Economic Community (EEC). Statistical analysis was carried out by a statistician, not directly involved in the study. T0, T1, T2, and T3 refer respectively to pre-treatment, after one, two and three weeks of treatment.
EXAMPLE 1
In 33 patients affected by chronic hepatitis following C virus infection (anti-HCV+) the administration of one sachet per day (3 g of the composition containing 60% by weight of Streptococcus thermophilus and 40% by weight of Lactobacillus plantarum) induced a reduction of the aspartate aminostransferase (AST) from 52±32 IU at TO to 45±27 IOU at T2, of the alanine aminotransferase (ALT) from 68±39 IU at TO to 58±31 IU at T2 and of gamma-glutamyltranspeptidase (gGT) from 52±49 IU at TO to 40±25 IU at T2. In the above patients the following symptoms improved during and/or the treatment: anorexia, itching, nausea, diarrhea, constipation and insomnia. No undesired reactions or side-effects were noted. In 21 of the above patients, AST, ALT, and/or gGT resulted normalized at T3. As control group, 26 patients were treated with 15 capsules per day of Infloran Berna (trade mark), a marketed preparation of Bifidobacerium bifidum (1×109 bacterial per capsule) and Lactobacillus acidophilus (1×109 bacteria per capsule). The usual recommended daily dose of Infloran is 3 capsules per day; therefore the experiments were carried out administering a five fold increased dosage of Infloran. Apart from the poor compliance on the treated patients, no subject evidenced any significant variation in the AST, ALT and gGT levels at T3 (AST from 54±30 in AT to TO 55±31 IU; ALT from 65±34 IU at TO to 64±31 IU at T2 and gGT from 51±37 IU at TO to 55±41 IU at T2. The difference among the two groups was always statistically significant with p values <0.05.
EXAMPLE 2
In 24 subjects with serum cholesterol levels at TO of 268±126 mg/dl two sachets (6 gr per day of the composition comprising 68% by weight of Streptococcus thermophilus, 28% by weight of Lactobacillus casei and 4% by weight of maltodextrin) were administered, and at T3 the levels were reduced to 219±175 mg/dl (p<0.5). In the control group treated with 15 capsules of Infloran per day, the serum cholesterol levels did not change (from 254±156 mg/dl at TO to 250±168 mg/dl at T3)_.
EXAMPLE 3
Fifteen patients with irritable bowel syndrome were treated for 2 weeks with a sachet (3 g of the composition of Example 1) per day. Before and after the treatment colonscopy was performed and multiple endoscopic biopsies, at least 2 samples in each site, were taken in the descending and sigmoid colon. On biopsy specimens histological studies have shown a reduced number of infiltrating inflammatory cells. In the faeces of the same patients the measurement of tumor necrosis factor alpha has shown that the levels of this cytokine are reduced following the treatment with the preparation, from 45±12 pg/ml to faecal supernatant to 12±5 pg/ml (p<0.01).
EXAMPLE 4
In 18 healthy volunteers, the following parameters were evaluated before, during and at the end of the administration of one sachet (3 g) per day. In this study, the composition per gram was:
    • 31% by weight of lyophilized Streptococcus thermophilus, 7×1011
    • 7% by weight of lyophilized Lactobacillus casei, 1×1011
    • 8% by weight of lyophilized Lactobacillus plantarum, 1×1011
    • 7% by weight of lyophilized Lactobacillus acidophilus, 2×1010
    • 8% by weight of lyophilized Lactobacillus delbrueckii sub-species bulgaricus, 3×109,
    • 27% by weight of a mixture of lyophilized Bifidobacteria, 38×1010,
    • 12% by weight of microcrystalline cellulose.
T0 T1 T2 T3
CHOLESTEROL (mg/dl)
average 190.6 179.0 174.4 184.2
Maximum 285.3 264.8 247.5 267.4
Minimum 108.3 118.1 108.6 113.6
SD 59.9 44.7 44.0 54.3
AST (IU/ml)
average 29.8 25.8 26.0 23.3
Maximum 97.3 88.1 81.5 59.1
Minimum 13.2 6.8 10.8 10.8
SD 23.1 22.0 19.1 13.7
ALT (IU/ml)
average 31.9 31.2 26.6 24.5
Maximum 131.6 132.6 99.1 91.0
Minimum 10.1 7.1 7.5 6.7
SD 34.5 35.4 26.3 24.1
gG T (IU/ml)
average 41.2 40.3 37.5 38.5
Maximum 127.0 137.8 129.1 125.6
Minimum 12.3 12.5 9.2 9.7
SD 34.3 37.1 35.4 34.3
NK Activity (12.5:1)
average 44.0 67.5 49.9 41.0
Maximum 62.0 97.0 62.0 56.0
Minimum 24.0 47.0 25.0 14.0
SD 12.2 16.9 11.4 14.1
NK Activity (25:1)
average 56.4 80.5 54.6 48.1
Maximum 66.0 100.0 69.0 63.0
Minimum 42.0 51.0 37.0 23.0
SD 9.8 13.3 9.5 12.0
NK Activity (50:1)
average 60.8 87.8 59.1 51.8
Maximum 74.0 100.0 65.0 63.0
Minimum 48.0 69.0 42.0 30.0
SD 7.5 10.5 6.9 11.1
CD4 TO CD8 CELL RATIO
average 1.45 1.75 1.64 1.27
Maximum 2.71 4.10 4.32 2.76
Minimum 0.96 1.05 0.97 0.58
SD 0.57 0.87 0.95 0.60

In the above subjects, fecal examination showed a mean increase of lactobacillus species from <1×106 colony forming units (CFU) per gram of fecal material to 64×106 CFU and of bifidobacteria species from <1×106 CFU to 68×106.
Preparations of the Strains
Strains used in the following formulation, given by way of example only, are as follows:
    • thermophile Streptococci (ATCC 19987) consists of a mixture of two strains from a yogurt culture and a starter used for preparation of cheeses;
    • Lactobacillus delbrueckii sub-species bulgaricus (ATCC 7994) is represented by a strain isolated from a yogurt culture;
    • Lactobacillus acidophilus (ATCC 43121) is present in a mixture consisting of two strains of human origin isolated from a special yogurt;
    • Bifidobacteria (Bifidobacterium infantis (ATCC 15697). Bifidobacterium longum (ATCC 15707), Bifidobacterium bifidum (ATCC 35914)) come from the intestinal flora of newborn babies;
    • Lactobacillus casei (ATCC 334) has been isolated from a culture employed in the production of cheeses, and
    • Lactobacillus plantarum (ATCC 8289) has been isolated from vegetables in progress of fermentation.
In order to obviate problems due to possible phage attacks, these strains can obviously be replaced by other cultures having the same features and origins, but provided with a different phage sensitiveness.
Culture Preparation
The individual strains maintained in a lyophilized and frozen form have been grown in synthetic media specific for each species. The fundamental component of the culture medium is permeate obtained by ultrafiltration of serum or milk, to which minimal amounts of biological activators are added depending on the species. After sterilization, the culture medium is inoculated with a strain per species or 1 to 3 strains belonging to the same genotype. Cultures have been incubated upon determination of optimal parameters for each strain: temperature, time, pH values and stirring.
Industrial cultures have been concentrated by centrifugation and lyophilization has been then carried out according to standard methodologies.
After lyophilization the cell mass has been pulverized under sterile conditions. The individual cultures submitted to chemical and microbiological tests have been maintained at 5° C. in hermetic vessels.
Preparation of the Individual Species
1) Streptococcus thermophilus (ATCC 19987)
Mother
The mother has been prepared by inoculating the strain in a medium consisting of 5% of permeate +1% of yeast extract and incubated at 44° C. over 3 hours.
Medium
Permeate 5%
Yeast extract 1%
Fermentation parameters
Fermenter: 72% 1 Applikon
Percent of inoculation: 1%
Incubation temperature 44° C.
Stirring speed 160 rpm
Neutralization set point pH = 6.00
Neutralizing substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 3 h 30 m
Final cooling: 24° C.
Concentration parameters
Centrifuge type: Westfalia SA1
Centrifugation temperature: 24° C.
flow rate: 24 l/h
(The concentrate was then centrifuged again using a
laboratory centrifuge at 6000 rpm over 20 minutes).
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400
Lyophilization protector: a solution of
lactose

Results: the number of microorganisms during the different steps of the process are reproduced in the following Table:
Steps U.F.C./g
End of fermentation 2.4E9
Concentrate 1.6E11
Lyophilized 7.4E11
U.F.C. = Colony-forming units
E9 = one thousand millions
E11 = one hundred thousand millions
No particular problems have been found in the preparation of this microorganisms. Therefore the cell loss during the different steps of the process could be greatly limited and a high bacterial charge could be achieved in the lyophilized product.
2) Lactobacillus plantarum (ATCC 8289)
Mother
Prepared in MRS culture medium and incubated at 33° C. over 5 hours.
Medium
Permeate 5%
Yeast extract 1%
Glucose 2.5%
Fermentation parameters
Fermenter: Applikon
Percent of inoculation: 1%
Incubation temperature 33° C.
Stirring speed 110 rpm
Neutralization set point pH = 6.00
Neutralizing substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 15 h

Cell inactivation after fermentation by pasteurization at 80° C. over 15 minutes.
Concentration parameters
Centrifuge type: Westfalia SA1
Centrifugation temperature: 60° C.
Flow rate: 40 l/h
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400
Lyophilization protector: a solution of
lactose

The number of microorganisms during the different process steps is reproduced in the following Table:
Steps U.F.C.G Count/g in
Thoma
End of fermentation 9.2E8 —
Lyophilized — 1.0E11
U.F.C. = colony-forming units
E8 = one hundred millions
E11 = one hundred thousand millions.
3) Lactobacillus casei (ATCC 334)
Mother
Prepared in MRS culture medium and incubated at 37° C. over 8 hours and 30 minutes
Medium
Permeate 5%
Yeast extract 1%
Glucose 1%
Fermentation parameters
Fermenter: Applikon
Inoculation percent: 1%
Incubation temperature 37° C.
Stirring speed 110 rpm
Neutralization set point pH = 5.40
Neutralizing substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 15 h
Concentration parameters
Centrifuge type: Westfalia SA1
Centrifugation temperature: 60° C.
Flow rate: 46 l/h
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400
Lyophilization protector: a lactose solution

Results: the number of microorganisms during the different process steps is reproduced in the following Table:
Steps U.F.C.G Count/g in
Thoma
End of fermentation 1.0E9 —
Lyophilized — 1.0E11
U.F.C. = Colony-forming units
E8 = one hundred millions
E11 = one hundred thousand millions.
4) Mixture of bifidobacteria (Bifodobacterium infantis (ATCC 15697)—Bifidobacterium longum (ATCC 15707)—Bifodobacterium bifidum (ATCC 35914), ratio 1:1:1 by weight)
Mother
The mother has been prepared by inoculating the strains in a medium consisting of 10% of powdered skimmed milk +0.5% of glucose +1% of yeast extract and incubated at 38° C. over 15 hours.
Medium
Permeate 4%
Yeast extract 1%
Bacto Soytone 0.25%
Glucose 0.5%
Fermentation parameters
Fermenter: Applikon
Inoculation percent: 2%
Incubation temperature 38° C.
Stirring speed 110 rpm
Neutralization set point pH = 6.00
Neutralizing substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 15 h
Cooling at the end of fermentation: 24° C.
Concentration parameters
Centrifuge type: Westfalia SA1
Centrifugation temperature: 24° C.
Flow rate: 42 l/h
(The obtained concentrate has been then centrifuged again
with a laboratory centrifuge at 6000 rpm over 20 minutes)
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400

Lyophilization protector: a solution of powdered skimmed milk+yeast extract+lactose+sodium maleate has been prepared.
Results: the number of microorganisms during the different process steps is reproduced in the following Table:
Steps U.F.C.G
End of fermentation 1.7E9
Concentrate 7.0E10
Lyophilized 3.8E11
U.F.C. = Colony-forming units
E9 = one thousand millions
E10 = ten thousand millions
E11 = one hundred thousand millions.
In this case too, in which bacteria are considered of “hard” growing, no particular problems have been found during the different preparation steps and the number of microorganisms is high both in the fermentation and on the lyophilized.
5) Lactobacillus acidophilus (ATCC 43121)
Mother
Prepared in a medium consisting of 5% of permeate+1% of yeast extract+1% of glucose+1% of Tween (Registered Trademark) 80 and incubated at 37° C. over 15 hours.
Medium
Permeate 5%
Yeast extract 1%
Glucose 1%
Tween (Registered Trademark) 80 0.1%
Fermentation parameters
Fermenter: Applikon
Inoculation percent: 1%
Incubation temperature 37° C.
Stirring speed 110 rpm
Neutralization set point pH = 6.00
Neutralizing substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 15 h
Cooling at the end of fermentation: 24° C.
Concentration parameters
Centrifuge type: Westfalia SA1
Centrifugation temperature: 24° C.
Flow rate: 42 l/h
(The obtained concentrate has been then centrifuged again
with a laboratory centrifuge at 6000 rpm over 20 minutes)
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400

Lyophilization protector: a solution of lactose and anhydrous mixture consisting of powdered skimmed milk+yeast extract+lactose+sodium maleate+Tween (Registered Trademark) 80. Results: the number of microorganisms during the different process steps is reproduced in the following Table:
Steps U.F.C./g
End of fermentation 2.9E8
Concentrate 2.3E10
Lyophilized 2.0E10
U.F.C. = Colony-forming units
E8 = one hundred millions
E10 = ten thousand millions
6) Lactobacillus delbrueckii sub-species bulgaricus (ATCC 7994)
Mother
Prepared in a medium consisting of 5% of permeate+1% of yeast extract+1% of beef extract+1% of glucose+0.1% of Tween (Registered Trademark) 80 and incubated at 44° C. over 4 hours and 30 minutes.
Medium
Permeate 5%
Yeast extract 1%
Beef extract 1%
Glucose 1%
Tween (Registered Trademark) 80 0.1%
Fermentation parameters
Fermenter: Applikon
Inoculation percent: 1%
Incubation temperature 44° C.
Stirring speed 110 rpm
Neutralization set point pH = 5.60
Neutralization substance type: ammonium hydrate
(sol to 10%)
Fermentation time: 7 h
Cooling at the end of fermentation: 24° C.
Concentration parameters
Installation: pilot unit for Hydro Air Research
microfiltration with two serial ceramic diaphragms each
having a 0.2 m2 filtrating surface.
Microfiltration temperature 30° C.
Operating conditions recirculation
flow rate 4000 l/h
input pressure
2.7 bar
output pressure
1.2 bar
average flow of
the permeate 30 l/h × m2
(The obtained concentration has been then centrifuged again
with a laboratory centrifuge at 6000 rpm over 20 minutes).
Lyophilization
Lyophilizer Edwards MINI -
FAST 3400

Lyophilization protector: a solution of lactose and anhydrous mixture consisting of powdered skimmed milk+yeast extract+lactose+sodium glutamate+Tween (Registered Trademark) 80. Results: the number of micoorganisms during the different process steps is reproduced in the following Table:
Steps U.F.C./g
End of fermentation 2.9E9
Concentrate 2.4E10
Lyophilized 3.5E9
U.F.C. = Colony-forming units
E9 = one thousand millions
E10 = ten thousand millions

Claims (33)

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 aid 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.
US11/375,704 1992-02-10 2006-03-15 Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use Expired - Lifetime USRE40023E1 (en)

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US98383992A 1992-12-01 1992-12-01
US11775193A 1993-09-08 1993-09-08
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE41276E1 (en) * 1996-03-11 2010-04-27 Vsl Pharmaceuticals, Inc. Strains of bacteria and pharmaceutical composition containing one or more of such strains and use of same for preventing and treating diseases associated with or caused by altered metabolism of bile acids
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Families Citing this family (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ369297A3 (en) * 1995-05-23 1998-05-13 Smithkline Beecham Plc Process for preparing liquid aromatized pharmaceutical preparation
US6899872B1 (en) * 1995-11-27 2005-05-31 Standa Lab Sa Absorbable dietary composition for improving the biological balance of intestinal tract flora
IT1288119B1 (en) 1996-06-28 1998-09-10 Renata Maria Anna Ve Cavaliere DIETARY COMPOSITIONS TO BE USED IN FEEDING VIA ENTERICA
US8828432B2 (en) * 1996-10-28 2014-09-09 General Mills, Inc. Embedding and encapsulation of sensitive components into a matrix to obtain discrete controlled release particles
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ES2283027T3 (en) * 1996-11-29 2007-10-16 Bio K + International Inc. LACTIC FERMENT THAT INCLUDES A PARTICULAR CEPA OF LACTOBACILUS ACIDOFILUS AND USE OF THE SAME.
EP0856259B1 (en) * 1996-12-23 1998-08-12 SITIA-YOMO S.p.A. Composition for feed use comprising lyophilized live lactic bacteria
US6098795A (en) * 1997-10-14 2000-08-08 Mollstam; Bo Device for adding a component to a package
SE510813C2 (en) * 1997-12-08 1999-06-28 Arla Ekonomisk Foerening Bacterial strain of the species Lactobacillus Paracasei subsp. paracasei, its composition for use in food, and product containing the strain
DE69941212D1 (en) * 1998-03-23 2009-09-17 Gen Mills Inc PLASTERING COMPONENTS IN EDIBLE PRODUCTS
US7201923B1 (en) * 1998-03-23 2007-04-10 General Mills, Inc. Encapsulation of sensitive liquid components into a matrix to obtain discrete shelf-stable particles
US6368591B2 (en) * 1998-05-15 2002-04-09 Shanghai Sine Pharmaceutical Corporation Ltd. Beneficial microbe composition, new protective materials for the microbes, method to prepare the same and uses thereof
US7029702B2 (en) * 1998-07-07 2006-04-18 Ritter Natural Sciences Llc Method for increasing lactose tolerance in mammals exhibiting lactose intolerance
FR2785809B1 (en) 1998-11-18 2001-01-12 Gervais Danone Sa SELECTION AND USES OF STRAINS OF LACTIC BACTERIA MODULATING NON-SPECIFIC IMMUNITY
IT1304170B1 (en) 1998-12-15 2001-03-08 Novartis Nutrition Ag ORGANIC COMPOUNDS
US20040161422A1 (en) * 1999-04-30 2004-08-19 Natarajan Ranganathan Nutritional compositions comprising probiotics
US20040105848A1 (en) * 1999-04-30 2004-06-03 Natarajan Ranganathan Enteric dialysis compositions and methods
US7998470B2 (en) * 1999-04-30 2011-08-16 Kibow Biotech, Inc. Compositions and methods improving renal function
IT1311495B1 (en) * 1999-06-09 2002-03-13 Mendes S U R L COMPOSITION INCLUDING ALKALINE SPHYNOMYELINASE, USABLE AS A DIETARY PRODUCT, FOOD SUPPLEMENT OR MEDICATION.
US8697051B2 (en) 1999-06-09 2014-04-15 Vsl Pharmaceuticals Inc. Composition comprising alkaline sphingomyelinase for use as a dietetic preparation, food supplement or pharmaceutical product
US20040166101A1 (en) * 1999-09-22 2004-08-26 Bojrab Gregory G. Enchanced composition for treatment of gastrointestinal disorders and hyperlipidemia
US6641808B1 (en) * 1999-09-22 2003-11-04 Lacpro Industries, Llc Composition for treatment of obesity
US6696057B1 (en) 1999-09-22 2004-02-24 Lacpro Industries, Inc. Composition and method for treatment of gastrointestinal disorders and hyperlipidemia
US6444203B2 (en) 1999-12-20 2002-09-03 Compagnie Gervais Danone Administering bacteria to improve sleep
US20030130217A1 (en) * 2000-02-23 2003-07-10 Eyal Raz Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation
IL151345A0 (en) * 2000-02-23 2003-04-10 Univ California Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation
MXPA02009342A (en) * 2000-03-24 2003-09-22 Nestle Sa Use of lactic acid bacterium for the treatment of peritonitis.
KR20020043078A (en) * 2000-12-01 2002-06-08 한인규 Oligosaccharide and Probiotics Complex
WO2003013558A1 (en) * 2001-07-30 2003-02-20 Claudio De Simone Treatment of radiation-induced diarrhea with probiotics
US20030091971A1 (en) * 2001-09-14 2003-05-15 Invitrogen Corporation Composition for stabilizing biological materials
FR2831395B1 (en) * 2001-10-25 2004-06-11 Triballat Laiteries PROCESS FOR THE PRODUCTION OF FERMENTED SOYBEAN PRODUCTS, FERMENTED PRODUCTS OBTAINED THEREBY AND CORRESPONDING FERMENTS
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US11103542B2 (en) * 2002-03-13 2021-08-31 Kibow Biotech, Inc. Composition and method for maintaining healthy kidney function
DE10223856A1 (en) * 2002-05-28 2003-12-18 Nutrinova Gmbh Anti-inflammatory and chemopreventive
US7431986B2 (en) * 2002-07-24 2008-10-07 General Mills, Inc. Encapsulation of sensitive components using pre-emulsification
AU2003282494A1 (en) * 2002-10-11 2004-05-04 Wyeth Nutritional formulations containing synbiotic substances
ITMI20022343A1 (en) * 2002-11-05 2004-05-06 Biofarm Srl FAST DISSOLUTION FILM IN WATER, CONTAINING COSMETIC, AROMATIC, PHARMACEUTICAL OR FOOD SYSTEMS.
ATE354964T1 (en) * 2003-05-22 2006-03-15 Synbiotics Ab PROBIOTIC COMPOSITION CONTAINING AT LEAST TWO STRAINS OF LACTIC ACID BACTERIA THAT ARE CAPABLE OF COLONIZING THE GASTROINTESTINAL TRACT AND, IN COMBINATION, HAVE THE PROPERTIES OF SURVIVE IN THE INTESTINAL, BINDING TO THE INTESTINAL, PROTECTING AGAINST INFECTION AND FERMENTING FIBER
WO2005076824A2 (en) * 2004-02-03 2005-08-25 The Regents Of The University Of California Methods of treating irritable bowel syndrome
WO2006012536A2 (en) * 2004-07-22 2006-02-02 Ritter Andrew J Methods and compositions for treating lactose intolerance
US7803413B2 (en) 2005-10-31 2010-09-28 General Mills Ip Holdings Ii, Llc. Encapsulation of readily oxidizable components
DE102005062731A1 (en) * 2005-12-22 2007-06-28 Organobalance Gmbh New Lactobacillus strains and their use
FR2895877B1 (en) * 2006-01-06 2012-06-22 Gervais Danone Sa FERMENTED MILK POWDER OR YOGURT WITH HIGH DENSITY IN LACTIC FERMENTS
US20070255598A1 (en) * 2006-03-29 2007-11-01 Mccarthy Nancy J Compliance aid, kits comprising the compliance aid, and methods of use
US20110165127A1 (en) * 2006-06-09 2011-07-07 Fabiola Masri Dairy-derived probiotic compositions and uses thereof
US8304226B2 (en) 2006-08-22 2012-11-06 Carl Miller Quality of life of hepatitis C patients with a formulation for administration to the oral mucosa including freeze dried lysate of selected Lactobacillus or Bifidobacterium species and N-acetyl D-glucosamine
US8007783B2 (en) * 2006-08-22 2011-08-30 Carl Miller Quality of life for hepatitis C patients with a formulation for administration to the oral mucosa including Lactobacillus delbrueckii subsp. bulgaricus and N-acetyl D-glucosamine
WO2008036719A2 (en) * 2006-09-19 2008-03-27 Powlen Owen J Animal feed supplements and uses thereof
US20110223248A1 (en) * 2007-12-12 2011-09-15 Ritter Pharmaceuticals, Inc. Methods and compositions for treating lactose intolerance
US20110189148A1 (en) * 2008-06-25 2011-08-04 Ritter Pharmaceuticals, Inc. Lactose compositions with decreased lactose content
WO2010098822A1 (en) 2009-02-24 2010-09-02 Ritter Pharmaceuticals, Inc. Prebiotic formulations and methods of use
DK2228436T3 (en) 2009-03-06 2016-04-11 Dupont Nutrition Biosci Aps The centrifugation and filtration methods for concentrating micro-organisms
EP2437616A4 (en) * 2009-06-05 2013-08-21 Gen Mills Inc Encapsulated omega-3 fatty acids for baked goods production
WO2011044516A2 (en) * 2009-10-09 2011-04-14 Prothera, Inc. Compositions and methods comprising pediococcus for reducing at least one symptom associated with autism spectrum disease in a person diagnosed with an autism spectrum disease
EP2533803B1 (en) 2010-02-11 2016-01-20 Technische Universität München Lactocepins for use in the treatment of ip-10-mediated inflammatory diseases
WO2011137249A1 (en) 2010-04-28 2011-11-03 Ritter Pharmaceuticals, Inc. Prebiotic formulations and methods of use
EP2532354A1 (en) 2011-06-08 2012-12-12 OrganoBalance GmbH Spray-dried lactobacillus strains/cells and the use of same against helicobacter pylori
MX354047B (en) * 2011-06-08 2018-02-09 Novozymes As SPRAY-DRIED <i>LACTOBACILLUS</i> STEMS / CELLS AND THE USE OF SAME AGAINST <i>HELICOBACTER PYLORI.
EP2804613A4 (en) * 2012-01-16 2015-12-09 Elizabeth Mckenna Compositions and methods for the treatment of hepatic diseases and disorders
US20140086849A1 (en) 2012-09-21 2014-03-27 Elizabeth McKenna Naturally-Occurring CpG Oligonucleotide Compositions and Therapeutic Applications Thereof
MX370537B (en) 2013-02-07 2019-12-17 Novozymes As Composition comprising lactobacillus and a carrier.
ITMI20131467A1 (en) 2013-09-06 2015-03-07 Sofar Spa USE OF A COMPOSITION INCLUDING MICRO-ORGANISMS TO INCREASE THE INTESTINAL PRODUCTION OF BUTIRRIC ACID, FOLIC ACID OR NIACINE ACID AND / OR TO REDUCE THE INTESTINAL PRODUCTION OF SUCCINIC ACID
AU2015258769A1 (en) * 2014-05-12 2016-12-01 Medlab Ip Pty Ltd Probiotic compositions and uses thereof for treatment of obesity-related disorders
DK3209308T3 (en) 2014-10-24 2022-10-03 Evolve Biosystems Inc ACTIVATED BIFIDOBACTERIA AND METHODS OF USING THEREOF
CN116270760A (en) * 2015-03-13 2023-06-23 英凡特健康有限公司 Composition for metabolizing or sequestering free sugar monomers and use thereof
MA45288A (en) 2016-06-08 2019-04-17 Sofar Spa New medical use of probiotics
IT201600127498A1 (en) 2016-12-16 2018-06-16 Sofar Spa PROBIOTICS FOR USE IN DIVERTICULOSIS AND DIVERTICULAR DISEASE
US11179426B2 (en) 2016-12-29 2021-11-23 Kibow Biotech, Inc. Composition and method for maintaining healthy kidney function
WO2020018482A1 (en) * 2018-07-16 2020-01-23 Stc.Unm Treatment methods and compositions
US20220160794A1 (en) * 2019-05-14 2022-05-26 Ormendes Sa Use of bacillus amyloliquefaciens and/or bacillus subtilis for the enhancement of active probiotic compositions or for the activation of inactive probiotic compositions, compositions thus obtained, and related method
US20230148645A1 (en) 2020-04-09 2023-05-18 Prabhakaran PANDURANGAN Therapeutic composition

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4115199A (en) * 1977-05-04 1978-09-19 Chr. Hansen's Laboratory, Inc. Preparation of culture concentrates for direct vat set cheese production
US4205132A (en) * 1978-07-17 1980-05-27 Microlife Technics, Inc. Lyophilization of bacteria
US4226940A (en) * 1979-06-21 1980-10-07 Great Lakes Biochemical Co., Inc. Non-frozen concentrated bacterial cultures
US4588595A (en) * 1982-11-09 1986-05-13 Morinaga Milk Industry Co., Ltd. Culture containing a viable cell mass of Bifidobacteria and lactic acid bacteria
EP0228881A2 (en) * 1985-12-20 1987-07-15 Roger A. Draft Tank overfill valve
FR2609044A1 (en) * 1986-12-30 1988-07-01 Sperimentaledel Latte Centro LACTIC FERMENTS IN SYMBIOTIC ASSOCIATION AND THEIR USE IN THE PREPARATION OF DAIRY, CHEESE AND FOOD PRODUCTS IN GENERAL
EP0291578A1 (en) * 1987-05-20 1988-11-23 Kopalnia Soli "Wieliczka" Table salt enriched in bioelements
IT1200625B (en) * 1985-05-30 1989-01-27 Sitia Yomo Spa Immuno-stimulating compsn.
US4806368A (en) * 1987-09-16 1989-02-21 Reddy Malireddy S Shelf life and subsequent growth of lactobacillus acidophilus, propionibacterium shermanii and leuconostoc citrovorum in dietary fiber based supplement preparation
US4913913A (en) * 1987-02-25 1990-04-03 The Calpis Food Industry Co., Ltd. Method of preparation of bifidobacteria-containing fermented milk
US5108766A (en) * 1990-10-22 1992-04-28 Pierre Gelinas Flavorants for enhancing the taste and flavor of bakery products and process of making
US5128260A (en) * 1989-01-12 1992-07-07 Sanofi Bio Ingredients, Inc. Process for preparing culture concentrates for direct vat set dairy products production
US5143845A (en) * 1986-09-03 1992-09-01 Toa Pharmaceutical Co., Ltd. Mixture of saccarifying lactic acid producing and butyric acid producing bacteria
US5219597A (en) * 1991-02-20 1993-06-15 Korea Food Research Institute Method for producing highly concentrated, lactic-acid fermented product utilizing unground grainy rice and improving qualities thereof by the secondary, enzymatic treatment at fermentation
US5474932A (en) * 1991-07-25 1995-12-12 Probi Ab Intestine colonizing strains of lactobacilli

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0696538B2 (en) * 1985-12-19 1994-11-30 株式会社アドバンス Anti-carcinogen

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4115199A (en) * 1977-05-04 1978-09-19 Chr. Hansen's Laboratory, Inc. Preparation of culture concentrates for direct vat set cheese production
US4205132A (en) * 1978-07-17 1980-05-27 Microlife Technics, Inc. Lyophilization of bacteria
US4226940A (en) * 1979-06-21 1980-10-07 Great Lakes Biochemical Co., Inc. Non-frozen concentrated bacterial cultures
US4588595A (en) * 1982-11-09 1986-05-13 Morinaga Milk Industry Co., Ltd. Culture containing a viable cell mass of Bifidobacteria and lactic acid bacteria
IT1200625B (en) * 1985-05-30 1989-01-27 Sitia Yomo Spa Immuno-stimulating compsn.
EP0228881A2 (en) * 1985-12-20 1987-07-15 Roger A. Draft Tank overfill valve
US5143845A (en) * 1986-09-03 1992-09-01 Toa Pharmaceutical Co., Ltd. Mixture of saccarifying lactic acid producing and butyric acid producing bacteria
FR2609044A1 (en) * 1986-12-30 1988-07-01 Sperimentaledel Latte Centro LACTIC FERMENTS IN SYMBIOTIC ASSOCIATION AND THEIR USE IN THE PREPARATION OF DAIRY, CHEESE AND FOOD PRODUCTS IN GENERAL
US4913913A (en) * 1987-02-25 1990-04-03 The Calpis Food Industry Co., Ltd. Method of preparation of bifidobacteria-containing fermented milk
EP0291578A1 (en) * 1987-05-20 1988-11-23 Kopalnia Soli "Wieliczka" Table salt enriched in bioelements
US4806368A (en) * 1987-09-16 1989-02-21 Reddy Malireddy S Shelf life and subsequent growth of lactobacillus acidophilus, propionibacterium shermanii and leuconostoc citrovorum in dietary fiber based supplement preparation
US5128260A (en) * 1989-01-12 1992-07-07 Sanofi Bio Ingredients, Inc. Process for preparing culture concentrates for direct vat set dairy products production
US5108766A (en) * 1990-10-22 1992-04-28 Pierre Gelinas Flavorants for enhancing the taste and flavor of bakery products and process of making
US5219597A (en) * 1991-02-20 1993-06-15 Korea Food Research Institute Method for producing highly concentrated, lactic-acid fermented product utilizing unground grainy rice and improving qualities thereof by the secondary, enzymatic treatment at fermentation
US5474932A (en) * 1991-07-25 1995-12-12 Probi Ab Intestine colonizing strains of lactobacilli

Non-Patent Citations (20)

* Cited by examiner, † Cited by third party
Title
A. Onderdonk et al, Obstetrics and Gynecology, "Quantitative and Qualitative Effects of Douche Preparation on Vaginal Microflora", 80, (1992), pp. 333-338. *
Bifidobacteria microflora, vol. 1, No. 1, pp. 3-24, 1982, F. Mitsuoka, "Recent Trends in Research on Intestinal Flora". *
Bifidobacteria Microflora, vol. 3, No. 1, pp. 29-33, 1984, T. *
D. Triger, Journal of Hepatology, "Endotoxemia in Liver Disease-Time for Re-Appraisal?" 12, (1991), pp. 136-138. *
Database WPI, Derwent Publications, AN-89-119459, Sep. 4, 1987, JP-A-1 066 124, Mar. 13, 1989. *
Fernandes et al, FEMS Microbiology Reviews, "Therapeutic Role Dietary Lactobacilli and Lactobacillic Fermented Dairy Products" 46, (1987), pp. 343-356. *
G. Kaklij et al, L Cancer Letters, "Antitumor Activity of Streptococcus thermophilus against Fibrosacoma: Role of T-cells", 56, (1991), pp. 37-43. *
G. Molin et al, Antonie Van Leeuwenhoek, "Effect of Fermented Oatmeal Soup on the Cholesterol Level and the Lactobacillus Collonization of Rat Intestinal Mucosa", 61, (1992), pp. 167-173. *
G.W. Elmer et al, JAMA, Vo. 275, pp. 870-876 (1996). *
H. Goris et al, Microecology and Therapy, "Intestinal Flora Associated Endotoxin", 14, (1984), p. 267 (Abstract Only). *
H. Kitazawa et al, Microbiol. Immunol., "Interferon Induction in Murine Peritoneal Macrophage by Stimulation with Lactobacillus acidophilus", 36, (1992), pp. 311-315. *
H. Sawada et al, Agric. Biol. Chem., "Purification and Characterization of an Antihypertensive Compound from Lactobacillus casei", 54, pp. 3211-3219. *
Kageyama, et al, The Effect of Bifidobacterium Administration in Patients with Leukemia. *
M. Hall et al, Archives of Disease in Childhood, "Factors Influencing the Presence of Faecal bactobacilli in Early Infancy" 65, (1990), pp. 185-188. *
Microecology and Therapy, vol. 14, pp. 109-126, 1984, Y. Kawai, "Effect of Cellular Extracts of Streptococci on Hyper-lipidemia in Rats, Rabbits, and Humans". *
Microecology and Therapy, vol. 16, pp. 271-271, 1986, D. Muting, et al, "Bifidobacterium Bifidus Adminsitration in Humans: A Controlled Clinical Study in Liver cirrhosis". *
N. Suegara, et al, "Hypolipidermic Effect of Streptococcus faecalis Kawai in Humans and Mechanisms of Serum Lipid Reduction", Microecology and therapy, vol. 15, pp. 271-280, 1985. *
Patent Abstracts of Japan, vol. 9, No. 309 (C-318), Dec. 5, 1985, JP-A-60 149 527, Aug. 7, 1985. *
S. Klebanoff et al, J. Exp. Med. "Viricidal Effect of Lactobacillus acidophilus on Human Immunodeficiency Virus Type 1: Possible Role in Heterosexual Transmission", 174, (1991), pp. 289-292. *
S. Klebanoff et al, The Journal of Infectious Diseases, "Control of the Microbial Flora of the Vagina by Hydrogen Peroxide-Genrating Lactobacilli", 184, (1991), pp. 94-100. *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE41276E1 (en) * 1996-03-11 2010-04-27 Vsl Pharmaceuticals, Inc. Strains of bacteria and pharmaceutical composition containing one or more of such strains and use of same for preventing and treating diseases associated with or caused by altered metabolism of bile acids
US20110217368A1 (en) * 2009-05-01 2011-09-08 Satya Prakash Bacterial compositions for prophylaxis and treatment of degenerative disease
US10660857B2 (en) * 2009-05-01 2020-05-26 Uas Laboratories Llc Bacterial compositions for prophylaxis and treatment of degenerative disease

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