WO1996026732A1 - Compositions of lactic acid bacteria and saccharomyces lysates and the therapeutical use thereof - Google Patents

Compositions of lactic acid bacteria and saccharomyces lysates and the therapeutical use thereof Download PDF

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Publication number
WO1996026732A1
WO1996026732A1 PCT/EP1996/000558 EP9600558W WO9626732A1 WO 1996026732 A1 WO1996026732 A1 WO 1996026732A1 EP 9600558 W EP9600558 W EP 9600558W WO 9626732 A1 WO9626732 A1 WO 9626732A1
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Prior art keywords
combinations
saccharomyces
lysates
lactobacillus
component
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PCT/EP1996/000558
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French (fr)
Inventor
Celestino Ronchi
Fabio Berlati
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Newpharma S.R.L.
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Publication of WO1996026732A1 publication Critical patent/WO1996026732A1/en

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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
    • A61K35/745—Bifidobacteria
    • 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
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • 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
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast

Definitions

  • the present invention relates to combinations of lactic acid bacteria and Saccharomyces lysates and/or glucans, the use thereof as immunostimulating agents and pharmaceutical compositions containing them.
  • Lactic Acid Bacteria hereinafter referred to as LAB, which comprise, inter alia. Lactobacilli (among which Acidophylus . Bulgaricus . Delbreukii , Fermentum. Casei ) , Streptococci (among them, Thermophylus .. Bifidobacteria (Longum. Biphydus . Pullorum. inter alia) and sporogenous lactobacilli, such as Lactobacillus sporogenes .
  • Lactobacilli among which Acidophylus . Bulgaricus . Delbreukii , Fermentum. Casei
  • Streptococci among them, Thermophylus .. Bifidobacteria (Longum. Biphydus . Pullorum. inter alia)
  • sporogenous lactobacilli such as Lactobacillus sporogenes .
  • LAB besides being a direct source of Vitamins of the groups B, D, K, and the like, act through a mechanism of competitive antagonism against microorganisms, patho ⁇ genic and/or opportunists, which, in particular conditions, have affected the normal intestinal bacterial flora (Bottazzi, Zacconi, Sarra, Probiotica con Batteri Lattici, Centro Sperimentale del Latte, Milan, Italy).
  • Bacteria are known to have (Sharon et Lis, Carbohydrates in Cell recognition - Sci. Am.-Jan. 93) a cell wall characterized by the presence of specific polysaccharides which allow for the bacterium itself to adhere to the intestinal epythelium, the latter being characterized in turn by analogue polysaccharide receptors. The presence of said receptor sites contributes to establish the antagonism among the various bacteria, when the micro-climatic conditions vary (pH, redox potential).
  • polysaccharides present on the cell walls are of different nature, but polysaccharides deriving from mannan, characterized by ⁇ l-6, 1-2 and 1-3 bonds, from glucans ( ⁇ l-3 polyglucose) are always present.
  • annans (Technical Publication n. 113 Alltech Inc. Nicholasville, KY, U.S.A.) can be used to favourably change the intestinal ecosystem by competitively inhibiting the adhesion sites which could be used as adhesion and colonization points by pathogenic microorganisms.
  • Fructans and glucans (polyfructose and polyglucose, respectively) were employed as an alternative to mannans, with the same purposes. Fructans turned out to be easily fermentable by a great number of microorganisms which on the contrary cannot hydrolyse glucans (only some species of microorganisms can hydrolyse and ferment glucans).
  • mannans are known (Technical Publication n. 113 Alltech Inc. Nicholasville, KY, U.S.A.) to have a strong stimulating action in the growth of such LAB as Bifidobacteria, Lactic acid bacteria and Streptococci. Disclosure of the invention
  • a combination comprising: a) lactic acid bacteria; b) Saccharomyces lysates; and optionally c) glucans, being it possible to replace component b) with component c).
  • a further object of the present invention is provided by pharmaceutical compositions containing the combination as the active ingredient.
  • lactic acid bacteria or LAB as herein meant, comprise lactic acid bacteria in a broad sense.
  • LABs are examples of LABs.
  • Saccharomyces lysates can be obtained by methods known to those skilled in the art, see for instance J. A. Reynolds et al., Infection and Immunity, Oct. 1980, vol. 30, n. 1, p. 51-57 and the literature therein cited.
  • Glucans of different purity can be obtained by known methods and are also commercially available.
  • the ratio of component a) to component b), the latter optionally in admixture with component c), or of component a) to component c), ranges from 1:1,000 to 1:0.001.
  • the lysate is obtained from Saccharomyces cerevisiae.
  • the LAB is selected from the group consisting of L. acidophylus. L_. bulgaricus. or a combination thereof, L. ther ophylus.
  • the immunostimulating action of glucan being known (J. A. Reynolds et al. - Glucan-Induced Enhancement of Host Resistance to Selected Infectious Diseases, Infect. et Immun. 30, 1, 51-57 - Oct. 1980) (Kokoshis et al. - Increased Resistance to Staphylococcus aureus Infection and Enhancement in Serum Lysozy e Activity by Glucan - Scie. 199, March 24, 1978), the action on the immune system of the single components of the combination (LAB and Saccharomyces cerevisiae lysates) was evaluated.
  • Saccharomyces lysates (glucans) ⁇ > 15%) and with LAB only (> 70%). The actions exerted by Saccharomyces cerevisiae lysate and that of glucans were not substantially different.
  • compositions containing the combination of the invention in admixture with conventional carriers and excipients.
  • the compositions can be solid, such as tablets (prompt-release or controlled-released ones), coated tablets (film-coated, gastro-resistant, controlled-release, sugar-coated pills), effervescent or fast-dissolution tablets, chewable tablets, soft- and hard-gelatin capsules, sugar-coated pills; or they can be liquid, such as solutions, suspensions, syrups, elixirs, granulates for suspensions or solutions to be reconstituted.
  • compositions according to the invention can be prepared with techniques known to those skilled in the art, for example as described in "Remington's Pharma ⁇ ceutical Sciences Handbook, XVII Ed., Mack Pub., N.Y., U.S.A..
  • the daily dosages will be established by the physician, depending on the disease to treat and the conditions of the patient (age, sex, weight).
  • the doses can range as follows:
  • Saccharomyces lysates 0.1 mg/dose to 1 g/dose; glucans: 0.1 mg/dose to 1 g/dose.
  • the daily dose can vary from 1 dose/day to 5 doses/day.
  • the compositions and the medicaments can be used both in human and veterinary medicines.
  • compositions of the invention for the improvement of the immune responses in man and animals can be used not only for therapeutic, but also for prophylactic purposes.
  • the present invention also comprises dietetic and food compositions containing the combination described above.
  • the following examples further illustrate the invention.
  • One capsule contains: Lactobacilli Acidophylus and Bulgaricus 10 billion Saccharomyces lysates 100 mg Lactose 500 mg
  • One tablet contains:
  • Lactobacilli Acidophylus and Bulgaricus 20 billion Saccharomyces lysates 300 mg
  • One dosage unit contains:

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Combinations of lactic acid bacteria and Saccharomyces lysates are described having immunostimulating activity, the use thereof in human and veterinary medicine and pharmaceutical compositions containing them.

Description

COMPOSITIONS OF LACTIC ACID BACTERIA AND SACCHAROMYCES LYSATES AND THE THERAPEUTICAL USE THEREOF
The present invention relates to combinations of lactic acid bacteria and Saccharomyces lysates and/or glucans, the use thereof as immunostimulating agents and pharmaceutical compositions containing them. Technological background
Lactic Acid Bacteria, hereinafter referred to as LAB, which comprise, inter alia. Lactobacilli (among which Acidophylus . Bulgaricus . Delbreukii , Fermentum. Casei ) , Streptococci (among them, Thermophylus .. Bifidobacteria (Longum. Biphydus . Pullorum. inter alia) and sporogenous lactobacilli, such as Lactobacillus sporogenes . have been used for a long time in pharmaceutical, dietetic or food products and administered to restore bacteria flora in dysmicrobisms of various nature, for example due to antibiotic therapies or to diseases of the gastro-intestinal tract (Bottazzi, Zacconi, Sarra, Probiotica con Batteri Lattici, Centro Sperimentale del Latte, Milan, Italy). LAB, besides being a direct source of Vitamins of the groups B, D, K, and the like, act through a mechanism of competitive antagonism against microorganisms, patho¬ genic and/or opportunists, which, in particular conditions, have affected the normal intestinal bacterial flora (Bottazzi, Zacconi, Sarra, Probiotica con Batteri Lattici, Centro Sperimentale del Latte, Milan, Italy).
Bacteria are known to have (Sharon et Lis, Carbohydrates in Cell recognition - Sci. Am.-Jan. 93) a cell wall characterized by the presence of specific polysaccharides which allow for the bacterium itself to adhere to the intestinal epythelium, the latter being characterized in turn by analogue polysaccharide receptors. The presence of said receptor sites contributes to establish the antagonism among the various bacteria, when the micro-climatic conditions vary (pH, redox potential). The polysaccharides present on the cell walls are of different nature, but polysaccharides deriving from mannan, characterized by αl-6, 1-2 and 1-3 bonds, from glucans (βl-3 polyglucose) are always present.
It is known that annans (Technical Publication n. 113 Alltech Inc. Nicholasville, KY, U.S.A.) can be used to favourably change the intestinal ecosystem by competitively inhibiting the adhesion sites which could be used as adhesion and colonization points by pathogenic microorganisms. Fructans and glucans (polyfructose and polyglucose, respectively) were employed as an alternative to mannans, with the same purposes. Fructans turned out to be easily fermentable by a great number of microorganisms which on the contrary cannot hydrolyse glucans (only some species of microorganisms can hydrolyse and ferment glucans).
Moreover, mannans are known (Technical Publication n. 113 Alltech Inc. Nicholasville, KY, U.S.A.) to have a strong stimulating action in the growth of such LAB as Bifidobacteria, Lactic acid bacteria and Streptococci. Disclosure of the invention
It has surprisingly been found that, upon administration of a combination of LAB and Saccharomyces lysates containing glucans for the treatment of intestinal dysmicrobiosis, a significant increase in all of the blood elements, both formed and non formed, involved in the non-specific immune response
(macrophages, lymphocytes etc.) takes place.
Therefore, it is an object of the present invention a combination comprising: a) lactic acid bacteria; b) Saccharomyces lysates; and optionally c) glucans, being it possible to replace component b) with component c).
It is another object of the present invention the use of the combination as an immunostimulating agent.
It is still another object of the present invention the use of the combination as an active ingredient, optionally in the presence of other pharmacological agents, for the manufacture of a medicament useful to improve immune defences in man and in animals.
A further object of the present invention is provided by pharmaceutical compositions containing the combination as the active ingredient.
Detailed disclosure of the invention According to the present invention, lactic acid bacteria or LAB, as herein meant, comprise lactic acid bacteria in a broad sense. Examples of LABs are
Lactobacillus acidophvlus. L_. bulgaricus . L.. delbreukii.
L.. casei . L.. Fermentum. the Streptococcus genus, for example S_. thermophylus. Bifidobacteria, such as fi. longum. B. biphvdus. £. pullorum. the sporogenous genus, for example Lactobacillus sporogenes.
The Saccharomyces lysates can be obtained by methods known to those skilled in the art, see for instance J. A. Reynolds et al., Infection and Immunity, Oct. 1980, vol. 30, n. 1, p. 51-57 and the literature therein cited.
Glucans of different purity can be obtained by known methods and are also commercially available.
According to the present invention, the ratio of component a) to component b), the latter optionally in admixture with component c), or of component a) to component c), ranges from 1:1,000 to 1:0.001.
According to a first preferred embodiment of the present invention, the lysate is obtained from Saccharomyces cerevisiae.
According to another preferred embodiment of the present invention, the LAB is selected from the group consisting of L. acidophylus. L_. bulgaricus. or a combination thereof, L. ther ophylus. The immunostimulating action of glucan being known (J. A. Reynolds et al. - Glucan-Induced Enhancement of Host Resistance to Selected Infectious Diseases, Infect. et Immun. 30, 1, 51-57 - Oct. 1980) (Kokoshis et al. - Increased Resistance to Staphylococcus aureus Infection and Enhancement in Serum Lysozy e Activity by Glucan - Scie. 199, March 24, 1978), the action on the immune system of the single components of the combination (LAB and Saccharomyces cerevisiae lysates) was evaluated.
Thus, the immunostimulating action induced by the combination of LAB and Saccharomyces cerevisiae lysate and/or glucans was evidenced to be substantially higher than that found in the subjects treated with only
Saccharomyces lysates (glucans) ~> 15%) and with LAB only (> 70%). The actions exerted by Saccharomyces cerevisiae lysate and that of glucans were not substantially different.
Further controls proved that, in the treated subjects, the immune responses from subjects treated with only glucan and/or Saccharomyces lysate are statistically different from those obtained in subjects treated with the combinations of the two products. In fact, an increase in macrophages, as well as the presence of lymphocytes joined to an increase in lysozyme production moreover shown by the increase in the development of the cell endoplasmic reticulum. The oral administration of a combination of Saccharomyces cerevisiae lysates and/or glucans with LAB proved to be a simple, effective means to improve immune defenses in man and animals.
Such an administration can be carried out by use of pharmaceutical compositions containing the combination of the invention in admixture with conventional carriers and excipients. The compositions can be solid, such as tablets (prompt-release or controlled-released ones), coated tablets (film-coated, gastro-resistant, controlled-release, sugar-coated pills), effervescent or fast-dissolution tablets, chewable tablets, soft- and hard-gelatin capsules, sugar-coated pills; or they can be liquid, such as solutions, suspensions, syrups, elixirs, granulates for suspensions or solutions to be reconstituted.
The compositions according to the invention can be prepared with techniques known to those skilled in the art, for example as described in "Remington's Pharma¬ ceutical Sciences Handbook, XVII Ed., Mack Pub., N.Y., U.S.A.. The daily dosages will be established by the physician, depending on the disease to treat and the conditions of the patient (age, sex, weight).
By way of examples, the doses can range as follows:
LAB: 1 million of c.f.u./dose to 100 billion of c.f.u./dose;
Saccharomyces lysates: 0.1 mg/dose to 1 g/dose; glucans: 0.1 mg/dose to 1 g/dose.
The daily dose can vary from 1 dose/day to 5 doses/day. According to the present invention, the compositions and the medicaments can be used both in human and veterinary medicines.
The compositions of the invention for the improvement of the immune responses in man and animals can be used not only for therapeutic, but also for prophylactic purposes. For the latter, besides the above mentioned pharmaceutical compositions, the present invention also comprises dietetic and food compositions containing the combination described above. The following examples further illustrate the invention.
Example I Capsules
One capsule contains: Lactobacilli Acidophylus and Bulgaricus 10 billion Saccharomyces lysates 100 mg Lactose 500 mg
Magnesium Stearate 20 mg
Capsule coating:
Food gelatin Titanium dioxide.
Example 2
Tablets
One tablet contains:
Lactobacilli Acidophylus and Bulgaricus 20 billion Saccharomyces lysates 300 mg
Microcrystalline cellulose 600 mg
Talc 20 mg
Magnesium Stearate 10 mg
Example 3 Granulate sachets
One dosage unit contains:
Lactobacillus Thermophylus 10 billion
Saccharomyces lysates 100 mg
Saccharose 5,000 mg Orange flavour 30 mg
Example 4
Vials with dosage cap
Content of dosage cap:
- Lactobacillus Sporogenes Spores 500 million - Lactobacillus Thermophylus 500 million
Contents of vial:
- Saccharomyces C. lysates 200 mg
- Saccharose 2 g
- Methyl-p-hydroxybenzoate 0.0075 mg - Depurated water q.s. to ml 5.

Claims

1. Combinations comprising: a) lactic acid bacteria b) Saccharomyces lysates, and optionally c) glucans, being it possible to replace component b) with component c).
2. Combinations according to claim 1, wherein the lactic acid bacteria are selected from the group comprising the genera Lactobacillus, Streptococcus, Bifidobacteria and sporogenous lactobacilli.
3. Combinations according to claim 2, wherein the Lactobacillus is selected from the group consisting of Lactobacillus acidophylus , L. bulgaricus . L.. delbreukii. L_- casei, L_. Fermentum. or combinations thereof.
4. Combinations according to claim 2, wherein the Streptococcus is S. thermophylus.
5. Combinations according to claim 2, wherein the Sporogenous is Lactobacillus Sporogenes spores.
6. A combination according to claim 2, wherein the Bifidobacterium is selected from the group consisting of B. longum. B. biphvdus . B. pullorum o combinations thereof.
7. Combinations according to any one of the above claims, wherein the ratio of component a) to component b), the latter optionally in admixture with component c), or of component a) to component c), ranges from 1:1,000 to 1:0.001.
8. Combinations according to any one of the above claims, wherein the lysate is obtained from Saccharomyces cerevisiae.
9. The use of the combinations of claims 1-8 as immunostimulating agents.
10. The use of the combinations of claims 1-8 as active ingredient for the preparation of a medicament useful for the improvement of the immune defenses for the therapeutical or prophylactic purposes in man and animals.
11. Pharmaceutical compositions containing as the active ingredient the combinations of claims 1-8 in admixture with conventional carriers and excipients.
12. Compositions according to claim 11, selected from the group consisting of prompt-release tablets, controlled-release tablets, coated tablets, sugar-coated pills, effervescent or fast-dissolution tablets, chewable tablets, soft- and hard-gelatin capsules.
13. Compositions according to claim 11, selected from the group consisting of solutions, suspensions, syrups, elixirs, granulates for suspensions or solutions to be reconstituted.
14. A pharmaceutical composition in the form of capsules according to the claims 11-12, comprising for each capsule:
Lactobacilli Acidophylus and Bulgaricus 10 billion Saccharomyces lysates 100 mg
Lactose 500 mg
Magnesium Stearate 20 mg
Capsule coating:
Food gelatin Titanium dioxide.
15. A pharmaceutical composition in the form of tablet according to the claims 11-12, comprising for each tablet:
Lactobacilli Acidophylus and Bulgaricus 20 billion
Saccharomyces lysates 300 mg Microcrystalline cellulose 600 mg
Talc 20 mg
Magnesium Stearate 10 mg.
16. A pharmaceutical composition in the form of granulate according to the claims 11-12, comprising for unitary dose:
Lactobacillus Thermophylus 10 billion
Saccharomyces lysates 100 mg
Saccharose 5,000 mg
Orange flavour 30 mg.
17. A pharmaceutical composition in the form of vials with reservoir plug according to the claims 11-12, comprising: Content of dosage cap:
- Lactobacillus Sporogenes Spores 500 million - Lactobacillus Thermophylus 500 million
Contents of vial:
- Saccharomyces C. lysates 200 mg
- Saccharose 2 g
- Methyl-p-hydroxybenzoate 0.0075 mg - Depurated water q.s. to ml 5.
PCT/EP1996/000558 1995-02-28 1996-02-09 Compositions of lactic acid bacteria and saccharomyces lysates and the therapeutical use thereof WO1996026732A1 (en)

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ITMI95A000378 1995-02-28
ITMI950378A IT1274654B (en) 1995-02-28 1995-02-28 ASSOCIATIONS OF LACTIC FERMENTS AND SACCHAROMETIC LYSATES THEIR THERAPEUTIC USE AND COMPOSITIONS CONTAINING THEM

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WO1998026787A1 (en) * 1996-12-19 1998-06-25 The University Of New South Wales Prebiotics and probiotics
US5786343A (en) * 1997-03-05 1998-07-28 Immudyne, Inc. Phagocytosis activator compositions and their use
NL1010770C2 (en) * 1998-12-09 2000-06-13 Nutricia Nv Preparation containing oligosaccharides and probiotics.
WO2003070260A1 (en) * 2002-02-21 2003-08-28 Societe Des Produits Nestle S.A. A photoprotective orally administrable composition for skin
WO2007135278A2 (en) * 2006-05-19 2007-11-29 Lesaffre Et Compagnie Probiotic microorganism compositions, granules containing them, method for the preparation thereof and uses thereof
US8357663B2 (en) 2007-11-30 2013-01-22 The Ramaekers Family Trust Methods for enhancing fertility comprising administration of transfer factor
US20130122075A1 (en) * 2001-04-30 2013-05-16 The Ramaekers Family Trust Encapsulated transfer factor compositions and methods of use
US20130243829A1 (en) * 2010-10-01 2013-09-19 Joseph C. Ramaekers Enhancement of immune response by transfer factor
US20150104425A1 (en) * 2006-07-24 2015-04-16 CortControl, Inc. Medical food for high cortisol breast cancer
US9125874B2 (en) 2007-11-30 2015-09-08 The Ramaekers Family Trust Administration of transfer factor for improving reproductive health
US20150366941A1 (en) * 2014-06-19 2015-12-24 Cortcontrol Human disease treatment with medical food formulation
US10688139B2 (en) 2002-02-21 2020-06-23 Société des Produits Nestlé S.A. Orally administrable composition for the photoprotection of the skin

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998026787A1 (en) * 1996-12-19 1998-06-25 The University Of New South Wales Prebiotics and probiotics
US5786343A (en) * 1997-03-05 1998-07-28 Immudyne, Inc. Phagocytosis activator compositions and their use
NL1010770C2 (en) * 1998-12-09 2000-06-13 Nutricia Nv Preparation containing oligosaccharides and probiotics.
WO2000033854A1 (en) * 1998-12-09 2000-06-15 N.V. Nutricia Preparation that contains oligosaccharides and probiotics
US6783780B1 (en) 1998-12-09 2004-08-31 N.V. Nutricia Preparation that contains oligosaccharides and probiotics
EP1481682A1 (en) * 1998-12-09 2004-12-01 N.V. Nutricia Preparation that contains oligosaccharides and probiotics
US20130122075A1 (en) * 2001-04-30 2013-05-16 The Ramaekers Family Trust Encapsulated transfer factor compositions and methods of use
WO2003070260A1 (en) * 2002-02-21 2003-08-28 Societe Des Produits Nestle S.A. A photoprotective orally administrable composition for skin
US10688139B2 (en) 2002-02-21 2020-06-23 Société des Produits Nestlé S.A. Orally administrable composition for the photoprotection of the skin
WO2007135278A3 (en) * 2006-05-19 2008-05-15 Lesaffre & Cie Probiotic microorganism compositions, granules containing them, method for the preparation thereof and uses thereof
CN101448510A (en) * 2006-05-19 2009-06-03 乐斯福公司 Probiotic microorganism compositions, granules containing them, method for the preparation thereof and uses thereof
WO2007135278A2 (en) * 2006-05-19 2007-11-29 Lesaffre Et Compagnie Probiotic microorganism compositions, granules containing them, method for the preparation thereof and uses thereof
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