USRE40457E1 - Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis - Google Patents

Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis Download PDF

Info

Publication number
USRE40457E1
USRE40457E1 US11/484,026 US48402697A USRE40457E US RE40457 E1 USRE40457 E1 US RE40457E1 US 48402697 A US48402697 A US 48402697A US RE40457 E USRE40457 E US RE40457E
Authority
US
United States
Prior art keywords
composition
concentration
enteral
per gram
bifidobacterium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US11/484,026
Other languages
English (en)
Inventor
Renata Maria Anna Cavaliere Ved. Vesely
Claudio De Simone
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
VSL Pharmaceuticals Inc USA
Original Assignee
VSL Pharmaceuticals Inc USA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=11374503&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=USRE40457(E1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by VSL Pharmaceuticals Inc USA filed Critical VSL Pharmaceuticals Inc USA
Application granted granted Critical
Publication of USRE40457E1 publication Critical patent/USRE40457E1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
    • A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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
    • A23V2400/533—Longum
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/975—Kit

Definitions

  • the present invention relates to dietary compositions useful for enteral feeding.
  • the present invention also relates to the use of lactic acid bacteria to prepare enteral dietary compositions adapted to modify the composition of the human intestinal flora, to stimulate the immune system or ameliorate diarrhea or intestinal disturbances.
  • the present invention also relates to the use of a lactic acid bacteria composition as a supplementation to a foodstuff.
  • the present invention further relates to a kit comprising two containers, one containing a foodstuff and the other containing a lactic acid bacteria composition, which shall be supplemented to said foodstuff at the moment of consuming the same.
  • enteral formulations are utilized in patients with a hyper-metabolic state as effected by burns, trauma, surgery and in patients suffering from malnutrition, chronic illness and in patients suffering from disorders resulting from prolonged periods of reduced oral intake resulting from cerebral vascular accidents, gastrointenstinal diseases, or a comatose state.
  • enteral nutrition compositions may be administered orally or by tube feeding.
  • enteral compositions have provided benefits and advantages as compared to total parenteral nutrition (TPN).
  • TPN total parenteral nutrition
  • the recommendation of the use of enteral compositions is based on recent clinical findings that demonstrate that the use of elemental diets results in fewer complications, reduced patient length of stay in the intensive care unit (ICU), and reduced cost, when compared to TPN.
  • Elemental diets are composed of low molecular weight nutrients that require minimal digestive and absorptive capability.
  • the protein source consists of free amino acids and in particular essential and nonessential amino acids.
  • the carbohydrate portion of such compositions is typically composed of glucose and hydrolyzed cornstarch (maltodextrin), while the fat content is usually low and primarily consists of essential fatty acids.
  • These diets are characterized by minimal residue in the intestines, because of the efficient absorption of the nutrients provided in an elemental form.
  • IMPACT comprises arginine and caseinates as the protein source, maltodextrins as the carbohydrate source and menhaden oil and structured lipids as the lipids source. IMPACT therefore has been designed as a formulation specifically aimed to improve the patient's nutritional status and also their immunocompetence.
  • colonic mucosa cannot nourish itself from the blood is of utmost importance and explains why patients undergoing EN or TPN develop colonic mucosa atrophy within few days of the treatment (Roediges, W. E. W., Gut 21:793, 1980). As most often these patients receive antibiotics, also the flora present in the host's colon is modified or reduced. This allows potential pathogenic microorganisms to colonize the digestive system. The colonic mucosal atrophy and the overgrowth of potential pathogenic microorganisms are probably the two most important pathogenicity factors in the above mentioned patients, apart from post-operative and post-traumatic gastrointestinal disturbances, sepsis, and multiple organ failure.
  • IMPACT and other enteral formulations in their present form are not able and neither have they been conceived for replacing or supplementing the host's colon probiotic flora. For these reasons, diarrhea and other intestinal disturbances develop in patients treated with these products.
  • lactobacilli There is a few enteral diets containing lactobacilli. However, a low number of lactobacilli per gram or ml of composition is present. The number of lactobacilli is further reduced when these organisms pass through the gastrointestinal tract. Actually these formulations have a weak capability of promoting colonization of the colon in the treated subject.
  • WO 93/01823 discloses an oatmeal-based oral nutritional supplement fermented by Lactobacillus plantarum strain No. 299 (at a concentration of ⁇ 10 10 CFU per gram of freeze-dried product) and a feeding formulation for enteral nutrition containing the same strain of Lactobacillus plantarum at a concentration of 1.5 ⁇ 10 6 CFU per 100 ml of nutrition solution, along with proteins, carbohydrates, lipids, mineral and vitamins.
  • the disclosed composition is an enteral formulation with specific characteristics in terms of calories, proteins, fats, vitamins and minerals and supplemented with a lactobacillus strain.
  • the disclosed enteral formulation is not appropriate for the needs of all individuals, as evidenced by the fact that different enteral formulations are prescribed according to different needs, as can be deduced from the following well-known classification (McClure, S., Digest. Dis. Sci., 8:1153, 1992):
  • enteral dietary compositions which do not suffer from the drawbacks of conventional compositions. Specifically, there remains a need for enteral dietary compositions which are effective for modifying the composition of the intestinal flora and for immunostimulation and which prevent diarrhea and intestinal disturbances. There also remains a need for enteral dietary compositions which may be used to supplement existing enteral compositions.
  • compositions containing two or more lactic acid bacteria selected from Streptococcus thermophilus and Bifidobacterium longum each strain at a concentration equal to or greater than 1 ⁇ 10 11 CFU per gram of bacteria, do not suffer from the drawbacks of conventional enteral compositions, and may be used to modify the intestinal flora and/or stimulate the immune system of a patient in need thereof, while exhibiting a reduced tendency to cause diarrhea, intestinal or urinary disturbances.
  • the present invention provides enteral dietary compositions and oral nutritional supplements, which contain at least two or more lactic acid bacteria of a genus selected from the group consisting of Streptococcus thermophilus and Bifidobacterium longum .
  • the concentration of each lactic acid bacteria is equal to or greater than 1 ⁇ 10 11 CFU per gram of bacteria, where CFU means colony forming unit.
  • the concentration of each lactic acid bacteria is preferably 1 ⁇ 10 11 to 1 ⁇ 10 14 CFU/gram of bacteria, more preferably 1 ⁇ 10 11 to 1 ⁇ 10 12 CFU/gram of bacteria.
  • compositions comprising two or more lactic acid bacteria selected from: Streptococcus thermophilus and Bifidobacterium longum , each strain at a concentration equal to or greater than 1 ⁇ 10 11 CFU per gram of bacteria.
  • the composition may in addition also include one or more strains from the group consisting of Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus plantarum , and Lactobacillus bulgaricus , each at a concentration equal to or greater than 1 ⁇ 10 10 CFU/gram of bacteria, preferably 1 ⁇ 10 10 to 1 ⁇ 10 13 CFU/gram of bacteria.
  • the enteral dietary composition comprises the combination of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis at a total bacterial concentration of 0.5 to 1.5 ⁇ 10 12 CFU per gram of bacteria.
  • the bacteria can be live, freeze-dried or heat-killed (80° C. per 5 min), according to different embodiments of the invention.
  • live freeze-dried lactic acid bacteria the composition may be employed to modify the ecology of the gut and to stimulate the immune system.
  • the heat-killed lactic acid bacteria may be used to stimulate the immune system alone or even in combination with other immunomodulants or vaccines.
  • the problem of the survival of the live bacteria in the stomach is overcome by the high number of the bacteria, and by possible administration of the composition by naso-enteric tube, by-passing the gastric acidity.
  • the bacteria can also be encapsulated in capsules and the patient can swallow them.
  • compositions are not required to contain any specific strains of the above-mentioned lactic acid bacteria, specific examples of suitable strains are set out in Table I below.
  • composition according to the present invention is preferably in a dry powder form, but it may also be prepared in any form suitable for administration to an individual in need of treatment.
  • the composition may alternatively comprise a liquid composition comprising the lactic acid bacteria in a liquid carrier which is pharmaceutically acceptable and which is non toxic for the bacteria.
  • the liquid carrier may comprise water, and the concentration of the bacteria will be between 1 ⁇ 10 11 and 1 ⁇ 10 13 lactic acid bacteria per ml of liquid.
  • the dry form of the composition preferably comprises between 1 ⁇ 10 11 to 1 ⁇ 10 14 lactic acid bacteria per gram of the total weight of the composition.
  • the composition of the present invention will comprise the bacteria in admixture with a carrier.
  • the composition includes, in addition to the lactic acid bacteria as aforesaid, a carrier comprising the residue of a suitable growth medium for the above mentioned bacteria, which growth medium residue obviously is non-toxic to humans.
  • the dry, powdered composition may further contain an added carrier such as aminoacids, sugars, salts, milk derivatives, inulin, oligosaccharides.
  • the composition may contain 0 to 20 wt.
  • the present composition may be prepared by either suspending the bacteria in a liquid preparation or dry-mixing the bacteria in a powder composition.
  • compositions are advantageous as compared to those of WO 93/01823, since the present compositions contain a higher number of bacterial strains.
  • the present compositions contain the bacteria at a concentration which is at least one order of magnitude greater than those of WO 93/01823.
  • the compositions of the present invention even though they may contain different excipients, are not required to be administered as a fermented nutrient composition (i.e. in the form of oatmeal), and are expressly made to modify the properties of all enteral formulations and/or oral nutritional supplements available now and in the future.
  • compositions of the present invention are also advantageous as compared to the relative feeding formulation for enteral nutrition containing the same strain of Lactobacillus plantarum at a concentration of 1.5 ⁇ 10 6 CFU in 100 ml of nutrition solution along with proteins, carbohydrate, lipids source, minerals and vitamins, since they can be added to all the commercially available formulations—general formulations and speciality formulations—changing and improving their properties.
  • the present compositions contain more strains of bacteria and a concentration of bacteria markedly different.
  • composition can be differently diluted leaving to the physician and/or the patient the liberty to select which bacteria concentration is to be fed per day, depending on the requirements of the individual and/or the disease prevention or treatment.
  • the present invention provides a method of enteral feeding comprising feeding a patient in need thereof with the present enteral dietary composition.
  • the composition be administered in such a regimen so that the patient receives 1 ⁇ 10 11 to 1 ⁇ 10 14 CFU/day, preferably 10 11 to 10 12 CFU/day, of the bacteria contained in the composition for a period of 1 to 365 days, preferably 1 to 90 days.
  • the patient receive 0.5 to 200 g, preferably 1 to 50 g, of the composition per day.
  • composition which contains heat-killed bacteria
  • the composition be administered in such an amount and at such a concentration to result in the immunostimulation of the patient.
  • Heat-killed bacteria too may be quantitated as CFU/g. In our hands, the best procedure was to quantitate the bacteria while alive, bring them to the desired concentration by lyophilization, and then kill them by heating.
  • the term “immunostimulation” means an increase of the peripheral blood lymphocyte count ( ⁇ 20%) with respect to the pre-treatment value and/or an increase of ⁇ 20% of the pre-treatment value of any parameter which is usually employed to assess specific and non-specific immunity ex vivo, i.e., TCD4 counts, immunoglobulin levels but not these parameters alone.
  • the administration of the composition according to the present invention will begin when the patient is unable or unwilling to consume an adequate diet, when the patient is in need of special nutritional needs (i.e., in case of renal, hepatic, cardiac diseases, cancer, etc.), when the patient has a temporary or permanent loss of the absorptive surface area of the intestine, when the patient has lost ⁇ 10% of the usual body weight, and when the patient is immunodepressed (i.e., skin test negative, low peripheral blood lymphocyte count, low TCD4 count and other immunologic tests).
  • the duration of the treatment will be determined by the physician and the amelioration of the clinical conditions will be observed according to the physician's clinical judgment and laboratory tests (i.e., lymphocyte counts, faecal flora examination, etc.).
  • the present enteral dietary composition may be administered orally, in a preferred embodiment the present composition is fed to the patient through a naso-enteric tube.
  • the bacteria in the present composition can more easily by-pass the acidity of the gut and survice to populate the intestines and the colon.
  • Suitable naso-enteric tubes and the use thereof are described in Ziegler, T., Scientific American , November 1995, which is incorporated herein by reference.
  • oral route is not excluded.
  • oral administration may be sufficient to result in immunostimulation.
  • compositions may be as simple as a mixture of the bacteria and an acceptable excipient.
  • an addition nutrition source such as an enteral or parenteral dietary formulation or oral nutritional supplements.
  • enteral and parenteral formulations are well known to those of skill i the art, and suitable examples are described in J. Parenter. Enter. Nutr., 1:14, 1993.
  • the conventional enteral or parenteral formulations need not necessarily be co-administered at exactly the same time as the dietary composition of the present invention. Rather, in a preferred embodiment, the conventional enteral formulation is fed through a naso-enteric tube first, followed by the feeding of the dietary composition of the present invention through the same naso-enteric tube. In this way, the bacteria of the present composition may adhere to the inside of the tube and may prevent or inhibit colonization of the tube by other, possibly pathogenic, bacteria. This same technique may be used to prevent the colonization of a catheter by pathogenic bacteria.
  • composition of the present invention can be added to any liquid, creamy or pasty foodstuff, for the purpose of obtaining foods capable of increasing, supplementing and balancing the intestinal flora.
  • composition of the present invention it is preferable for the composition of the present invention to be added to a liquid, creamy or pasty foodstuff directly by the consumer at the moment of use.
  • the present invention provides the use of a composition comprising two or more lactic acid bacteria selected from the group consisting of Streptococcus thermophilus and Bifidobacterium longum , each at a concentration equal to or greater than 1 ⁇ 10 11 CFU per gram of bacteria, as a supplementation to a liquid, creamy or pasty foodstuff, said supplementation being carried out at the moment of consuming the foodstuff.
  • the present invention provides a kit comprising:
  • the composition of the present invention is used as supplement to a foodstuff
  • many bacteria of the composition would not keep a viable form during the preservation; moreover, during the preservation of the foodstuff, some bacteria could cause fermentations, resulting in formation of or increase in acidity, thus rendering the foodstuff inacceptable from an organoleptic point of view.
  • the present invention is based on the discovery that lactic acid bacteria play several important roles in the gastrointestinal tract, such as:
  • CUC chronic ulcerative colitis
  • the composition was the same (ENSURE) for both groups,—Group A and Group B, except the supplementation of Streptococcus thermophilus, Bifidobacterium longum , and Bifidobacterium infantis (ratio 1:1:1) at a concentration of 1 ⁇ 10 12 CFU per gram of bacteria, to Group B.
  • the bacteria were live, freeze-dried.
  • the dosage was 6 grams of the preparation per day in only one administration. From a practical point of view, the bacteria were re-suspended in 10 ml of water and given by naso-enteric tube to the patient daily at a time included between 8 and 10 a.m., temporarily stopping the ENSURE administration.
  • the day of entrance into the study was defined as day 0.
  • the required feeding interval during which the patients had to receive the formulation was 10 days, beginning with day 0. After this feeding interval, the investigator was free to provide whatever feeding was felt to be appropriate for the remainder of the hospitalization. All patients received 5-ASA (2 grams per day) as standard treatment for CUC. Patients receiving mesalamine enemas before entry in the study continued the therapy. Antibiotic treatment was not initiated during the study unless indicated, for example for pulmonary or urinary tract infections, and antibiotic-treated patients were withdrawn from the trial. Acetaminophen, H2-receptor antagonists or alumin-based antiacids were given as needed.
  • Resolving colitis (B) exhibited reduction in the vascularity and disappearance of the acute inflammation and crypt abscesses with restoration of the goblet cell population within the epithelium and was accompanied by reactive hyperplasia of the epithelium, particularly at the base of the crypts.
  • PBMCs peripheral blood mononuclear cells
  • PBMCs peripheral blood mononuclear cells
  • ENSURE lactic acid bacteria plus ENSURE
  • CD3+/DR+ activated T lymphocytes
  • NK cells CD16+/CD56+
  • Cytotoxic NK-like T lymphocytes were also increased after the treatment as compared to pretreatment values (387 ⁇ 96 and 129 ⁇ 54 cells/ ⁇ l, respectively, P ⁇ 0.05).
  • HIV human immunodeficiency virus
  • All HIV+ subjects had Karnofsky performance scores of >50%.
  • Exclusion criteria for HIV+ subjects included physical or functional obstruction to food intake, opportunistic infection within the preceding 30 days, and other therapies whose objectives included weight gain or increased appetite.
  • the HIV+ subjects ranged in age from 28 to 44 years with a mean age of 35 ⁇ 6 years.
  • Six individuals were either homosexual or bisexual, and the remaining 14 had histories of intravenous drug use. All subjects had maintained standard medication regimens for at least a month prior to admission and continued to do so throughout the study. All subjects were receiving antiviral therapy at the time of admission (AZT, 500 mg/day) and continued with treatment throughout the study.
  • Sixteen patients received prophylaxis against Pneumocystic carinii prior to and during the study.
  • the patients were randomized in two groups and treated with NUTRINAUT, or with NUTRINAUT supplemented by the lactic acid bacteria composition for 3 weeks.
  • the bacterial composition contained Streptococcus thermophilus, Bifidobacterium longum , and Bifidobacterium infantis (ratio 1:1:1) at a concentration of 1 ⁇ 10 12 CFU per gram of bacteria, heat-treated at 80° C. for 5 min.
  • the bacteria were heat-killed and stored as a powder.
  • the dosage was 12 grams of the composition per day in two administrations/day. From a practical point of view, the bacteria were re-suspended in 10 ml of water and given by oral route.
  • the day of entrance into the study was defined as day 0.
  • the required feeding interval during which the patients had to receive the composition they were randomized to was 21 days, beginning with day 0. After this feeding interval, the investigator was free to provide whatever feeding was felt to be appropriate for the remainder of the hospitalization.
  • the immunocompetence of the patients was assessed by measuring the number of T CD4+ cells before and after the treatment, employing a monoclonal antibody against CD4 and a flow cytometer (Becton Dickinson).

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicinal Preparation (AREA)
US11/484,026 1996-06-28 1997-06-03 Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis Expired - Lifetime USRE40457E1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT96MI001329A IT1288119B1 (it) 1996-06-28 1996-06-28 Composizioni dietetiche da utilizzare nell'alimentazione per via enterica
PCT/IT1997/000127 WO1998000035A1 (en) 1996-06-28 1997-06-03 ENTERAL DIETARY COMPOSITIONS COMPRISING STREPTOCOCCUS THERMOPHILUS AND $i(BIFIDOBACTERIUM LONGUM)

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US08/952,820 Reissue US6077504A (en) 1996-06-28 1997-06-03 Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis

Publications (1)

Publication Number Publication Date
USRE40457E1 true USRE40457E1 (en) 2008-08-12

Family

ID=11374503

Family Applications (4)

Application Number Title Priority Date Filing Date
US11/484,026 Expired - Lifetime USRE40457E1 (en) 1996-06-28 1997-06-03 Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis
US08/952,820 Ceased US6077504A (en) 1996-06-28 1997-06-03 Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis
US09/525,940 Ceased US6326000B1 (en) 1996-06-28 2000-03-15 Kit with enteral dietary composition consisting of Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium longum
US11/484,027 Expired - Lifetime USRE39876E1 (en) 1996-06-28 2006-07-11 Kit with enteral dietary composition consisting of Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium longum

Family Applications After (3)

Application Number Title Priority Date Filing Date
US08/952,820 Ceased US6077504A (en) 1996-06-28 1997-06-03 Enteral dietary compositions comprising a mixture of live lactic bacteria consisting of Streptococcus thermophilus, Bifidobacterium longum and Bifidobacterium infantis
US09/525,940 Ceased US6326000B1 (en) 1996-06-28 2000-03-15 Kit with enteral dietary composition consisting of Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium longum
US11/484,027 Expired - Lifetime USRE39876E1 (en) 1996-06-28 2006-07-11 Kit with enteral dietary composition consisting of Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium longum

Country Status (17)

Country Link
US (4) USRE40457E1 (es)
EP (1) EP0847244B1 (es)
KR (1) KR100497770B1 (es)
AT (1) ATE199485T1 (es)
AU (1) AU724852B2 (es)
BR (1) BR9706554A (es)
CA (1) CA2227497C (es)
DE (1) DE69704194T2 (es)
DK (1) DK0847244T3 (es)
ES (1) ES2157074T3 (es)
GR (1) GR3035999T3 (es)
HU (1) HU225485B1 (es)
IT (1) IT1288119B1 (es)
NO (1) NO315542B1 (es)
PL (1) PL188804B1 (es)
PT (1) PT847244E (es)
WO (1) WO1998000035A1 (es)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170020936A1 (en) * 2011-07-21 2017-01-26 Biogaia Ab Production and Use of Bacterial Histamine

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE496989T1 (de) * 1997-02-11 2011-02-15 Entpr Ie Trd As Bioresearch Ie Probiotische stämme des lactobacillus salivarius und daraus hergestellte antimikrobielle mittel
KR20010075495A (ko) 1998-10-01 2001-08-09 추후보정 산화성 스트레스 인자의 감소
ID29150A (id) * 1999-01-15 2001-08-02 Entpr Ireland Cs Penggunaan lactobacillus salivarius
AU4905300A (en) * 1999-05-25 2000-12-12 Andrew W. Bruce Oral administration of lactobacillus for the maintenance of health in women
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
IT1311495B1 (it) * 1999-06-09 2002-03-13 Mendes S U R L Composizione comprendente sfingomielinasi alcalina, utilizzabile qualeprodotto dietetico, integratore alimentare o medicamento.
CN1186440C (zh) * 1999-08-05 2005-01-26 雀巢制品公司 预防病原性细菌引起的腹泻的新双歧杆菌
CA2281463A1 (en) * 1999-08-26 2001-02-26 Stanley H. Zlotkin Composition comprising micronutrients in combination with prebiotics, probiotics, and synbiotics
US7892586B2 (en) 2001-02-22 2011-02-22 Suzanne Jaffe Stillman Water containing soluble fiber
US8178150B2 (en) 2000-02-22 2012-05-15 Suzanne Jaffe Stillman Water containing soluble fiber
US7115297B2 (en) * 2000-02-22 2006-10-03 Suzanne Jaffe Stillman Nutritionally fortified liquid composition with added value delivery systems/elements/additives
JP3363438B2 (ja) 2000-05-02 2003-01-08 ビオフェルミン製薬株式会社 噴霧乾燥による菌体乾燥物
US20020044988A1 (en) * 2000-08-22 2002-04-18 Fuchs Eileen C. Nutritional composition and method for improving protein deposition
KR20020043078A (ko) * 2000-12-01 2002-06-08 한인규 올리고당이 포함된 복합생균제
US7101565B2 (en) 2002-02-05 2006-09-05 Corpak Medsystems, Inc. Probiotic/prebiotic composition and delivery method
EP1374878A1 (en) * 2002-06-20 2004-01-02 N.V. Nutricia Method and composition for preventing or alleviating symptoms of malabsorption from the gastrointestinal tract
WO2004037191A2 (en) * 2002-10-22 2004-05-06 University Of Vermont And State Agriculture College Symbiotic food products comprising oats and methods for manufacturing the same
CA2417943A1 (en) * 2003-01-31 2004-07-31 Tassos P. Anastassiades Weight gain and growth stimulation in mammals by n-acylated glucosamines
SE526711C2 (sv) * 2003-01-31 2005-10-25 Probi Ab Nya stammar av Bifidobacterium med förmåga att överleva i magtarmkanalen och producera glutamin in vivo, samt kompositioner och användningar därav
KR100568036B1 (ko) 2004-08-12 2006-04-07 하남주 장기능 활성화 및 면역기능 강화작용을 하는비피도박테리움 균주 및 이를 함유하는 생균제제
ES2284330B1 (es) * 2005-06-21 2008-07-16 Danone, S.A. Base acuosa no lactea, base acuosa fermentada obtenida a partir de la misma, refresco que contiene alguna de dichas bases y procedimiento para su obtencion.
ATE474585T1 (de) * 2005-10-06 2010-08-15 Nestec Sa Probiotische enterokokken für eine verbesserte immunität
EP1776877A1 (en) 2005-10-21 2007-04-25 N.V. Nutricia Method for stimulating the intestinal flora
JP5487379B2 (ja) * 2008-03-19 2014-05-07 森下仁丹株式会社 血中リン濃度上昇抑制剤
JP2013507394A (ja) * 2009-10-09 2013-03-04 プロセラ インコーポレイテッド 自閉症スペクトル障害と診断されたヒトにおいて自閉症スペクトル障害に関連する少なくとも一つの症状を低減するための、ペディオコッカス属を含む組成物及び方法
US11179426B2 (en) * 2016-12-29 2021-11-23 Kibow Biotech, Inc. Composition and method for maintaining healthy kidney function
FR3084255B1 (fr) * 2018-07-26 2020-07-03 Institut National De La Recherche Agronomique (Inra) Souche de streptococcus thermophilus cnrz160 pour le traitement et la prevention de l'inflammation intestinale et des desordres associes, chez un individu
KR102298782B1 (ko) * 2018-12-07 2021-09-07 대한민국 하수오 발효추출 조성물 및 이의 제조방법
KR102388388B1 (ko) * 2020-07-08 2022-04-21 김혁 탄수화물과 단백질이 함유된 쉐이크 및 이의 제조방법
CN113197312A (zh) * 2020-07-14 2021-08-03 内蒙古蒙牛乳业（集团）股份有限公司 嗜热链球菌mn002在免疫调节产品中的用途及膳食补充剂

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01228456A (ja) * 1988-03-09 1989-09-12 Snow Brand Milk Prod Co Ltd 生菌体カプセルの製造方法
EP0555618A2 (en) * 1992-02-10 1993-08-18 Renata Maria Anna Cavaliere Vesely Dietetic and/or pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use
US5310555A (en) * 1992-07-24 1994-05-10 Midwestern Bio-Ag Products And Services, Inc. Oral nutritional and dietary composition
US5494664A (en) * 1992-07-06 1996-02-27 Nestec S.A. Bifidobacteria
US5716615A (en) * 1992-02-10 1998-02-10 Renata Maria Anna Cavaliere Vesely Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3170215D1 (en) * 1980-12-29 1985-05-30 Monsanto Co Carbonylation process employing a catalyst stabilised in soluble form
JP2890746B2 (ja) * 1989-08-24 1999-05-17 日本油脂株式会社 高安定性腸内有用細菌を含有する食品

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01228456A (ja) * 1988-03-09 1989-09-12 Snow Brand Milk Prod Co Ltd 生菌体カプセルの製造方法
EP0555618A2 (en) * 1992-02-10 1993-08-18 Renata Maria Anna Cavaliere Vesely Dietetic and/or pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use
US5716615A (en) * 1992-02-10 1998-02-10 Renata Maria Anna Cavaliere Vesely Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use
US5494664A (en) * 1992-07-06 1996-02-27 Nestec S.A. Bifidobacteria
US5310555A (en) * 1992-07-24 1994-05-10 Midwestern Bio-Ag Products And Services, Inc. Oral nutritional and dietary composition

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
A. Venteri et al. Alimet. Pharmacol. Ther. 1999. pp. 1103-1108. *
Bazzocchi et al. Gastroenterology International. 1998. vol. 11, Suppl. 1. *
Elmer et al. "Biotherapeutic Agents". JAMA. Mar. 29, 1996, vol. 275, No. 1, pp. 870-876. *
Gionchetti et al. Gastroenterology International. 1998. vol. 11, Suppl. 1, pp. 108-110. *
Massimo Campieri et al. Gastroenterology. May 1999, vol. 116, No. 5, pp. 1246-1249. *
Saavedra et al. The Lancet. Oct. 15, 1994. vol. 344, pp. 1046-1049. *
Sandborn et al. Inflammatory Bowel Disease. Feb. 1999, vol. 5, No. 1, pp. 3-39. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170020936A1 (en) * 2011-07-21 2017-01-26 Biogaia Ab Production and Use of Bacterial Histamine
US10004770B2 (en) * 2011-07-21 2018-06-26 Biogaia Ab Production and use of bacterial histamine
US20180264055A1 (en) * 2011-07-21 2018-09-20 Biogaia Ab Production and Use of Bacterial Histamine
US10898529B2 (en) * 2011-07-21 2021-01-26 Biogaia Ab Production and use of bacterial histamine

Also Published As

Publication number Publication date
ITMI961329A1 (it) 1997-12-28
ES2157074T3 (es) 2001-08-01
DE69704194T2 (de) 2001-06-21
PL324643A1 (en) 1998-06-08
EP0847244A1 (en) 1998-06-17
AU3047697A (en) 1998-01-21
DE69704194D1 (de) 2001-04-12
USRE39876E1 (en) 2007-10-09
MX9801667A (es) 1998-08-30
NO976077D0 (no) 1997-12-23
ATE199485T1 (de) 2001-03-15
HU225485B1 (en) 2006-12-28
HUP9901619A1 (hu) 1999-08-30
DK0847244T3 (da) 2001-04-23
WO1998000035A1 (en) 1998-01-08
PT847244E (pt) 2001-06-29
CA2227497C (en) 2007-10-30
PL188804B1 (pl) 2005-04-29
KR19990035918A (ko) 1999-05-25
US6077504A (en) 2000-06-20
NO976077L (no) 1998-04-28
CA2227497A1 (en) 1998-01-08
IT1288119B1 (it) 1998-09-10
ITMI961329A0 (es) 1996-06-28
NO315542B1 (no) 2003-09-22
HUP9901619A3 (en) 2001-03-28
GR3035999T3 (en) 2001-09-28
US6326000B1 (en) 2001-12-04
AU724852B2 (en) 2000-10-05
EP0847244B1 (en) 2001-03-07
BR9706554A (pt) 1999-07-20
KR100497770B1 (ko) 2005-10-07

Similar Documents

Publication Publication Date Title
USRE39876E1 (en) Kit with enteral dietary composition consisting of Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium longum
US11116806B2 (en) Composite probiotic lactic acid bacteria powder and preparation method and use thereof
US7901925B2 (en) Lactobacillus delbrueckii ssp. bulgaricus strain and compositions
WO2022218336A1 (zh) 罗伊氏乳杆菌在制备预防或治疗发育障碍类疾病产品中的应用
JP4706016B2 (ja) 炎症性疾患治療におけるビフィドバクテリウム（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ）
JP2002534113A5 (es)
CN102118976A (zh) 用于经剖腹产分娩的婴儿的营养组合物
CZ300143B6 (cs) Kmen Lactobacillus, jeho použití a výrobek jej obsahující
TW200902040A (en) Probiotics in a pre-and/or post-surgical environment
WO2015093937A1 (en) Lactobacillus salivarius for the treatment of mastitis
CN111212575A (zh) 肌肉增量用组合物
CN110692885A (zh) 一种用于缓解便秘的益生菌保健饮料
CN108882740A (zh) 含有不可消化寡糖的发酵配方物
WO2006046871A2 (en) Peri-operative composition comprising lactobacillus rhamnosus
WO2008002484A2 (en) Novel lactobacillus bulgaricus strain and compositions
CN115466687B (zh) 一种降低体脂含量和体重的组合物及其应用
US20070298018A1 (en) Novel lactobacillus bulgaricus strain and compositions
MXPA98001667A (es) Composiciones dieteticas enterales que comprenden streptococcus thermophilus y bifidobacterium longum
BG112471A (bg) Имуномодулиращ синбиотичен състав
CN116509903A (zh) 一种增强免疫功能的合生元组合物及其应用
Li et al. Change of Lactobacillus and Bifidobacteria genera from breast milk to elders and their potential for preserving human health
EP2628394B1 (en) Probiotic functional food suitable for immunocompromised individuals undergoing treatment such as chemotherapy and/or radiotherapy
CN117343869A (zh) 一种动物双歧杆菌在制备降低心脏瓣膜手术术后并发症的产品中的应用
JP2021101645A (ja) 免疫バランスの調節のための組成物
Yaacob et al. LACTIC ACID BACTERIA IS BENEFICIAL FOR ORAL APHTHOUS ULCERATIONS-A PRELIMINARY REPORT

Legal Events

Date Code Title Description
CC Certificate of correction
FEPP Fee payment procedure

Free format text: PAT HOLDER CLAIMS SMALL ENTITY STATUS, ENTITY STATUS SET TO SMALL (ORIGINAL EVENT CODE: LTOS); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY

FPAY Fee payment

Year of fee payment: 12