WO2005077391A1 - New synbiotic use - Google Patents
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- WO2005077391A1 WO2005077391A1 PCT/SE2005/000220 SE2005000220W WO2005077391A1 WO 2005077391 A1 WO2005077391 A1 WO 2005077391A1 SE 2005000220 W SE2005000220 W SE 2005000220W WO 2005077391 A1 WO2005077391 A1 WO 2005077391A1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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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
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Definitions
- the invention relates to the use of at least two lactic acid bacterial strains selected from the group comprising Pediococcus pentosaceus 16:1 (LMG P-20608), Leuconostoc mesenteroides 23-77:1 (LMG P-20607), Lactobacillus paracasei subsp paracasei F-19 (LMG P-17806), and Lactobacillus plantarum 2362 (LMG P-20606) for the manufacturing of a formulation for the prevention or treatment of stress-induced inflammatory disorder.
- Pediococcus pentosaceus 16:1 LMG P-20608
- Leuconostoc mesenteroides 23-77:1 LMG P-20607
- Lactobacillus paracasei subsp paracasei F-19 LMG P-17806
- Lactobacillus plantarum 2362 LMG P-20606
- Such stress will most often result in an increased expression of certain immune system-related components in the body, which induces severe inflammation in various tissues of the body.
- Such an inflammation will significantly reduce the capacity of the im ate (natural) immune system and thereby decrease the individual resistance to disease, which makes the mammal prone to develop subsequent infections, but also, if prolonged stress, chronic diseases of various kinds.
- Some of these diseases are difficult to treat, and impossible to heal, as the existing medical medicaments for treatment of such diseases is much limited. This is especially true for chronic diseases, which constitute an increased burden to the Society. But also the treatment of acute conditions, such as infections is limited.
- Antibiotics for example have increasingly lost their ability to prevent and cure infections and septic manifestations such as systemic inflammatory syndrome (SIRS) and multiple organ failure (MOF), and might in addition lead to progress of antibiotic resistant infections. As far as can be judged, no new and more effective antibiotics are in the pipeline to reach the market. All presently existing applications to US Food and Drug
- Metabolic syndrome Central to the development of chronic diseases, but also influencing acute diseases, is the occurrence of a condition called metabolic syndrome (characterised by obesity, hypertension, insulin resistance, glucose intolerance and fatty infiltration of almost all organs, particularly the liver. Metabolic syndrome is a pre-stage of chronic diseases and a condition which today affects about 25 % of the population in countries like the US and the UK, and another 25 to 50 % are borderline/at risk to develop the condition. There is evidence that this condition is associated with over-consumption of calorie-condensed refined agricultural products and under-consumption of less calorie- condensed fruits, vegetables and live bacteria.
- the present formulation has shown a significant ability to improve the immune system and strengthen the body's resistance to diseases.
- the invention relates to the use of at least two lactic acid bacterial strains selected from the group comprising Pediococcu pentosaceus 16:1 (LMG P-20608), Leuconostoc mesenteroides 23-77:1 (LMG P-20607), Lactobacillus paracasei subsp paracasei F-19 (LMG P-17806), and Lactobacillus plantarum 2362 (LMG P-20606) for the manufacturing of a formulation for the prevention and/or treatment of stress-induced inflammatory disorder.
- the formulation may be a pharmaceutical formulation.
- the invention also relates to, a method of treating a mammal suffering from a stress-induced inflammatory disorder.
- the invention provides a completely new way of preventing and/or treating a mammal suffering from a stress-induced inflammatory disorder which in the case where the disorder is not treated it mostly continue into a chronic disease.
- stress-induced inflammatory disorder is intended to mean a phenomenon, in which a mammal, upon stress, increase the secretion of pro- and anti- inflammatory cytokines and acute phase proteins, increased infiltration of affected tissues with neutrophils, increased myeloperoxidase activity in the tissues affected, and increased oxidation of vital tissues, and increased accumulation in the tissues of oxidation products such as malonedealdehyde.
- APR acute phase reaction
- the term acute phase reaction is intended to mean a series of complex reactions which occur in the body under stress, mental or physical; infection, trauma, surgical operation, advanced medical treatment or delivery - all reactions aimed to provide optimal protection against progress of disease. They involve the whole body, but especially the central nervous system, the hypothalamus and the hypophysis, which via the so called neuro-endocrine axis activates all the organs in the body, particularly the adrenals, the thyroids, the gonads, the liver, the gut, its mucosa and lymphatic system but also to a large extent the intestines, the intestinal mucosa and the intestinal flora.
- APR Central to the APR is an enormously elevated release of various pro- and anti-inflammatory cells, to a large extent from cells which are not regarded as immune cells such as mucosal, endothelial and fat cells/adipocytes, but also by the flora, itself. Important is also the release of fibrinolysis-regulating substances, such as plasminogen activator inhibitor type 1 (PAI-1), which impairs the viscosity of blood, increase the coagulation, reduces the nutritive blood flow to the critical organs, such as the brain, the lungs and the liver, and often leads to formation of clots/thromboses. Characteristic to APR is increase in temperature, chill, somnolence, anorexia and profound changes in blood levels of plasma proteins, lipids, minerals, hormones, cytokines as well as cellular elements.
- PAI-1 plasminogen activator inhibitor type 1
- CPR chronic phase reaction
- APR and CPR hypermetabolism, increased hepatic glycogenesis (production of sugar by the liver), increased glucose turnover in the body, reduced muscle uptake of glucose, hyperlipidemia (too much fat in the circulation) and increased lipolysis of adipose tissues (breakdown of fat tissues and mobilisation to the circulation of), especially visceral fats, increased production of non-esterified fatty acids (NEFAs), increased protein synthesis in the liver and increased protein turnover in the body, increased blood glucose levels, increased insulin secretion and insulin resistance.
- NEFAs non-esterified fatty acids
- fibrinogen and PAI-1 are significantly elevated in CPR, and fibrinolysis (solubilisation disintegration of formed clots) significantly impaired.
- the formulation of the invention has the abilty to modulate/regulate: most often and in most organs inhibit, but occasionally also stimulate a number of different molecules involved in inflammation including phospholipase, lipooxygenase, cyclooxygenase 2 (COX-2), leukotreines, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte vchemoattractant protein- 1 (MCP-1), interferon-inducible protein, tumour necrosis factor (TNF), and interleukins such as interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 12 (IL-12), but also other interleukins.
- phospholipase lipooxygenase
- cyclooxygenase 2 COX-2
- leukotreines thromboxane
- prostaglandins
- NF-KB nuclear factor KB
- iNOS inducible nitric oxide synthase
- COX-2 COX-2 gene expression.
- An important function is also often an increased delivery to and availability in the tissues of pyruvate and of oxygen. Description It is well-known that when a mammal is under stress certain processes are triggered aimed to control the stress. Examples of functions, which are influenced by stress are among many others cytokines, myeloperoxidase activity, malondealdehyde accumulation and increase in accumulation of neutrophils in the affected tissues.
- LAB lactic acid bacterial
- the invention relates to a composition consist of the four above, mentioned LAB, or more.
- the lactic acid bacteria (LAB) to be used are selected after extensive studies of > 350 human fecal bacteria and about 180 bacteria harvested from fresh growing rye. After extensive studies of numerous functions of each lactic acid bacterium were the four most bioactive LAB (with ability to modulate inflammation) chosen for the composition.
- the bacterial strains may be administrated together with a pharmaceutically acceptable liquid component, but also as a powder or built into plasters or wound protecting tissues.
- the bacterial strains may be present in a concentration at least 10 6 CFU/ml, such as at least 10 7 , 10 s , 10 9 , 10 10 or at least 10 11 CFU/ml.
- one or more acceptable liquid component may be needed.
- Such components are well known to those skilled in the art.
- distilled water or buffered aqueous media are used, which contain pharmaceutically acceptable salts and buffers. Suitable salt solutions are PBS, PBSS, GBSS, EBSS, HBSS, and SBF.
- the liquid component can also be of a more hydrophobic nature in dependence of the application.
- the formulation may further comprise one or more therapeutic agents, such as an agent against the stress-induced inflammatory disorder. Accordingly the formulation may comprises the above mentioned four bacterial strains or even more, as long as the above mentioned bacterial strains are present.
- the formulation of the invention being used for to prevent or treat a mammal suffering from a stress-induced inflammatory disorder, such as a human being or an animal.
- the inflammatory disorders prevented or treated by the formulation may be chest/lung inflammation, urinary inflammation, vaginal inflammation, bowel inflammation, lever inflammation, stomach inflammation, muscle inflammation and brain inflammation. However, the inflammation may also be of another origin. Accordingly the formulation may further comprise at least one fibre.
- fibres such as plant fibres
- the combination of utilising fibre, such as plant fibres may release from the fibres numerous nutrients, antioxidants, growth-, coagulation and other factors, which in the body will modulate innate and eventually also adaptive immune defence mechanisms, hereby improving the body's ability to resist disease development.
- Fibres from fruits and vegetables have strong bioactivities by themselves. This is to maintain mucosal growth and functions, to maintain water and electrolyte balance, to provide energy and nutrients for the host, to provide energy and nutrients for the flora and to provide resistance against invading pathogens, which is further enhanced by the addition of the specific LAB as above.
- the fermentation process in the lower gastrointestinal tract releases through action of microbial enzymes numerous nutrients and antioxidants, but also various growths and coagulation-controlling as well as inflammation-controlling molecules.
- Antioxidants, but also other nutrients released in the lower GI tract by flora if existing and the supplied specific LAB, have significant pro-regenerative, antibacterial, antithrombotic, vasodilatory, anti-inflammatory and anti-carcinogenic effects.
- Nitric oxide is also released by fermentation by the LAB described above and is important for several bodily functions such as gastro-intestinal motility, blood flow, ventilation (dilatory effects) but also control of pathogenic microorganisms.
- fibres are beta-glucan, inulin, pectin, resistant starch, cellulose, hemicellulose, arabinoxylans, arabinogalactans, polyfructose, inulin, oligofructans, galacto-oligosacharides, gums, mucilages, pectins, dextrins, maltodextrins, potato dextrins, synthesised carbohydrates, polydextrose, methylcellulose, hydroxypropylmethylcellulose.
- Other examples from plants are fibres is selected from lignin substances from plants selected from the group comprising waxes, cutin, phytate, saponin, suberin and tannins.
- polymeric plant carbohydrates are beta-glucan, inulin, pectin and resistant starch.
- lactic acid bacteria By combining the four above mentioned lactic acid bacteria and the four fibres in the composition a unique and strong bioactivity as well a synergistic functions in the body are obtained.
- the components of this synbiotic composition show strong synergistic/potentiated health benefits both in experimental animals and in humans. A significant increase in these functions was observed when the chosen fibres were included in the composition.
- the formulation of the invention comprises at least one antioxidant, vitamin, mineral, amino acid, peptide or protein. Examples of such substances are antioxidant and vitamins, minerals, such as selenium and zinc, amino acids such as glutamine and arginine, and various peptides.
- vitamin C from various fruits and vegetables
- vitamin E from among others various grains, nutsand vegetarian oils, flavonols such as quercitin (from among others onion, apple, grapes, berries and broccoli), epigallocatechin (from among others tea leaves, especially green tee), epicatechin (from among others black grapes and red wine) flavonoids such as anthocyanidins (from among others various grapes, raspberries, strawberry, aubergine), oenine (from among others black grapes and red wine), hydrocinnamates such as p- coumaric acid from among others white grapes and tomatoes, spinach, asparagus and cabbage), ferulic acid (from among others grains, particularly oat, tomatoes, spinach, asperagus, and cabbage) carotenoids such as lycopene(such as from tomatoes
- the formulation may comprise glutamine or a synthetic version thereof.
- the invented formulation may be in the solid or liquid form such as tablet, gel spray, capsules or granulates. The form of the formulation is dependent on the use.
- the administration route of the formulation may be any route such as orally, ingested such as by tube fed, intraperitoneal, intramuscular or subcutaneous injection, or in case of tumors, intra-tumorally.
- Use of the formulation The invented formulation can be used to treat stress-induced inflammatory disorders, either acute or chronic.
- the stress may be induced by for example physical trauma, physical harm, an accident, burns, childbirth or poisoning or other forms of non-specified stress-induced trauma.
- disorders which can be prevented, include chest infections, such as those caused by the stress of reduced availability of oxygen (hypoxia), too high exposure to oxygen (hyperoxia), too high levels of sugar in blood (hyperglycemia), too low level of sugar in blood (hypoglycemia), irradiation, exposure to toxic chemical including certain pharmaceuticals and especially chemotherapeutic agents, trauma, pancreatitis, cystic fibrosis, viral, microbial, fungal and other infections and other pulmonary diseases and childbirth.
- the formulation may be used in stress-induced inflammatory disorders in the bowel and is also effective against inflammation induced by bacteria such as Helico- bacter, Clostridium difficile, HIV, rotavirus but also other microbial infections.
- the formulation may be used for preventing and treating postoperative morbidity.
- postoperative disorders are for example those caused by postoperative infections, which are triggered by stress-induced inflammation, most often in the lungs, but also in other organ systems, such as the urinary tract.
- immunomodulatory effects have been documented from supplementation of the composition.
- bioactive substances such as immunomodulins and beta-defensins are important properties of the formulation. These substances have the ability to down-regulate the exaggerated pro- inflammatory effect of pro-inflammatory cytokines, such as TNF and IL-6, but also other cytokines and pro-inflammatory substances such as acute phase proteins and oxidation-promoting substances such as homocysteine.
- Examples of groups of acute diseases, spontaneous or induced by advanced medical or surgical treatments, where the use of the formulation is beneficial are bone marrow or other transplantations, extensive medical and surgical treatments, thermic injuries, acute infections and general septic disorders.
- the use of the formulation according to the invention constitutes an inexpensive and powerful tool, which has no side effects, and the formulation can be used for long-term treatment of patients with a chronic disease.
- the formulation may be used for the treatment of a mammals, suffering from a stress-induced inflammatory disorder, such as a human being or animal, such as domestic animals.
- EXAMPLES The following illustrative examples show the unique documented effects obtained by using the medicament according to the invention.
- Example 1 Formulation One formulation was prepared consisting of Pediococcus pentosaceus 16:1 (LMG P-20608), Leuconostoc mesenteroides 23-77: 1 (LMG P-20607), Lactobacillus paracasei subsp paracasei F-19 (LMG P-17806), and Lactobacillus plantarum 2362 (LMG P-20606) at a concentration of 10 10 CFU/ml of each bacteria and 2.5 g of each beta-glucan, inulin, pectin and resistant starch (Ljung et al., 2002, Microb, Ecol, Health Dis, 3 (suppl):4 and Kruszewska et al, 2002, Microecol Ther 29:37.
- the formulation was produced by Medipharm AB, Kager ⁇ d, Sweden using the protocol by Ljung et al., as mentioned above.
- Example 2 Effect in Intensive Therapy (ITU) patients.
- ITU Intensive Therapy
- the IP increased continuously up to day 7 in all groups, except the group supplemented the above synbiotic formulation (group D), in which the L/M index from 0.439 (0.224- 0.626) on day 4 significantly (p ⁇ 0.05) dropped to 0.128 (0.088-0.320) on day 7.
- L/M index increased significantly (p ⁇ 0.02) in group A from 0.061 (0.010-0.379) on day 2 to 0.223 (0.076-0.705) on day 4 and was 0.515 (0.332-1.153) on day 7.
- Thirty four of totally 48 infections observed were chest infections, its incidence being significantly (p ⁇ 0, 03) lower in the group group treated with the synbiotic formulation (group D) than in the other groups.
- the patients supplemented with the symbiotic formulation did better than the others; had lower intestinal permeability, less translocation of pathogenic microorganisms and less chest infections (pneumonia).
- tPA tissue-type plasminogen activator
- PAI-1 plasminogen activator inhibitor type-1
- adipocytes have an increased expression of cytokines, especially of TNF ⁇ .
- the amount of fat in the abdomen can vary from a few milliliters to about six liters, which can explain the increased exposure of pro-inflammatory molecules, such as TNF ⁇ , in adipose individuals.
- pro-inflammatory molecules such as TNF ⁇
- ⁇ -interferon and underexpression of IL-10 sensitises the liver to both endotoxins and to toxic effects, especially of TNF ⁇ , which most likely is a key factor behind the progressive liver damage seen in patients with liver cirrhosis.
- the supply of the four lactic acid bacterial strains (probiotics, as defined in example 1) alone or in combination with the four polymeric carbohydrates (synbiotics, as defined in example 1) have the ability not only to reduce the production and absorption of endotoxin in the intestine, but also to down-regulate the production of pro-inflammatory cytokines, including TNF ⁇ .
- composition induces in patients with liver disease significant improvements in bilirubin and prothrombin activity as well as in albumin level.
- a long-term supply of a composition of four lactic acid bacteria strains and four polymeric carbohydrates reduces both the inflammation of the liver, the fatty infiltration of the liver (steatosis) and retards the progress of liver destruction.
- Example 7 Effect on gut colonisation, liver function and degree of encephalopathy in chronic liver disease.
- the synbiotic composition of four lactic acid bacteria strains and four polymeric carbohydrates was supplied during one month to patients with chronic liver disease and results compared to 15 similar patients, who received a placebo (non- fermentable, non-absorbable fibre) during the same time period.
- the intestinal pH was significantly reduced in the treatment group compared to placebo.
- Significant decreases in the number of Escherichia coli, Staphylococcus and Fusobacterium were observed.
- Significant decreases in ammonia(s), levels of endotoxin(s) and ALT (expression of impaired liver function) were observed in the group receiving the synbiotic composition, but not in the placebo group.
- the improvements in liver function observed in the group supplemented the synbiotic composition (as defined in example 1) were accompanied by significant improvements also in psychometric tests and in degree of encephalopathy.
- ICG R15 Indocyanine clearance test
- a supplementation with the synbiotic composition of four lactic acid bacteria strains (as defined in example 1) and four polymeric carbohydrates (as defined in example 1) resulted in a significant reduction in ICG R15 in the cirrhotic patients, an improvement most likely due to a reduced swelling of endothelial and sinusoidal cells and hereby reduced resistance to flow. Accordingly, a long-term supplementation of the synbiotic composition has the potential to reduce the number and the degree of severity of bleeding episodes in patients with liver cirrhosis.
- Example 9
- Example 11 Effects on chest infections. Several patients with cystic fibrosis have been treated with the composition of four lactic acid bacteria strains and four polymeric carbohydrates. There have all been in a rather late stage of disease, loosing weight, suffering diarrhea, and on almost constant antibiotic treatment. They have all made a dramatic turn around, diarrhea has been controlled, gained weight, and need of antibiotics been eliminated. The state of disease has improved. The synbiotic composition of four lactic acid bacteria strains (as defined in example 1) and four polymeric carbohydrates (as defined in example 1) has also been used in combination with the antioxidant curcumin (turmeric) and total disappearance of disease manifestations observed.
- Example 12 Effects when administered subcutaneously Abdominal infection was induced in experimental animals by a procedure called cecal ligation and puncture (CLP).
- CLP cecal ligation and puncture
- MDA Malondealdehyde
- Example 13 Effects when administered intraperitoneally The same experiments as in example 12 was performed, but the formulation/medicament applied intraperitonelly. Identical changes were observed.
- Example 14 Effects when administered intramuscularly The same experiments as in example 12 was performed, but the formulation/medicament applied intramuscularly. Identical changes were observed.
- Example 15. Effects when administered by inhalation The same experiments as in example 12 was performed, but the formulation/medicament applied by inhalation. Identical changes were observed.
- Example 16 Effects when administered by ingestion/oral supply The same experiments as in example 12 was performed, but the formulation/medicament applied by oral/enteral supply. Identical changes were observed.
- Example 17. Effects irradiation/chemotherapy-induced stress.
- Example 18 Effects of the formulation/medicament in patients with Clostridium difficile, HIV and rotavirus infections. Eighteen patients, children and adults, who suffered from manifest Clostridium difficile infections with chronic diarrhoea were supplemented daily with the medicament for minimum 30 days. All symptoms were relieved and no signs of Clostridium difficile observed on repeated examination of stool. Eight patients with manifest HIV, preferably children and suffering weight loss, severe diarrhoea and repeat infections, received for two weeks to 20 months oral daily intake of the medicament. They report increased well-being, reduced incidence of secondary infections, normalisation of stool frequency and consistency, and increased body weights. Five children suffering rotavirus diarrhoea received, in addition to liberal supply of fluid and salts also an oral supply of the medicament. The symptoms including diarrhoea disappeared within 2 days from institution of treatment.
- Example 19 Effects when applied topically in burns, chronic leg ulcers and bed sores and around skin-penetrating foreign materials. Thirty-five patients with infected burns on skin were treated with a gel of the synbiotic composition of four lactic acid bacteria strains and four polymeric carbo- hydrates. A dramatic reduction of infection and cleaning of the burned surfaces was observed. An improved healing could also be noted. In five patients the composition was used with further addition of curcumin and additional positive effects observed. Five patients with vaginitis were treated with a gel of the composition of four lactic acid bacteria strains and four polymeric carbohydrates. An instant cure was observed.
- IBS irritable bowel syndrome
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Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002555151A CA2555151A1 (en) | 2004-02-17 | 2005-02-17 | New synbiotic use |
AU2005212150A AU2005212150A1 (en) | 2004-02-17 | 2005-02-17 | New synbiotic use |
EP05711080A EP1715876A1 (en) | 2004-02-17 | 2005-02-17 | New synbiotic use |
US10/588,574 US20070286916A1 (en) | 2004-02-17 | 2005-02-17 | Synbiotic Use |
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SE0400355-4 | 2004-02-17 | ||
SE0400355A SE0400355D0 (en) | 2004-02-17 | 2004-02-17 | New synbiotec use |
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WO2005077391A1 true WO2005077391A1 (en) | 2005-08-25 |
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PCT/SE2005/000220 WO2005077391A1 (en) | 2004-02-17 | 2005-02-17 | New synbiotic use |
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US (1) | US20070286916A1 (en) |
EP (1) | EP1715876A1 (en) |
AU (1) | AU2005212150A1 (en) |
CA (1) | CA2555151A1 (en) |
SE (1) | SE0400355D0 (en) |
WO (1) | WO2005077391A1 (en) |
Cited By (14)
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WO2007040444A1 (en) * | 2005-10-06 | 2007-04-12 | Probi Ab | Method, device and computer program product for diagnosing of at least one exhaust emission control unit |
WO2011020853A1 (en) * | 2009-08-18 | 2011-02-24 | Cosucra-Groupe Warcoing Sa | Compositions containing mixtures of fermentable fibers |
WO2011009848A3 (en) * | 2009-07-20 | 2011-06-30 | Bracco Spa | Therapeutic use of probiotics |
AU2006299956B2 (en) * | 2005-10-07 | 2012-03-15 | Chr. Hansen A/S | Probiotics to influence fat metabolism and obesity |
WO2012170915A1 (en) | 2011-06-10 | 2012-12-13 | Prothera Inc. | Pharmaceutical compositions containing pediococcus and methods for reducing the symptoms of gastroenterological syndromes |
US8927252B2 (en) | 2011-02-09 | 2015-01-06 | Lavivo Ab | Synbiotic compositions for restoration and reconstitution of gut microbiota |
WO2015018883A2 (en) * | 2013-08-09 | 2015-02-12 | Ab-Biotics, S.A. | Probiotic for infantile excessive crying |
EP2294932B1 (en) | 2008-05-07 | 2015-10-21 | Vegenat, S.A. | Carbohydrate mixture and the use thereof for preparing a product for oral or enteral nutrition |
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DE19860375A1 (en) * | 1998-12-28 | 2000-07-06 | Aventis Res & Tech Gmbh & Co | Alpha amylase-resistant starch for the production of food and pharmaceuticals |
US7101565B2 (en) * | 2002-02-05 | 2006-09-05 | Corpak Medsystems, Inc. | Probiotic/prebiotic composition and delivery method |
-
2004
- 2004-02-17 SE SE0400355A patent/SE0400355D0/en unknown
-
2005
- 2005-02-17 CA CA002555151A patent/CA2555151A1/en not_active Abandoned
- 2005-02-17 EP EP05711080A patent/EP1715876A1/en not_active Withdrawn
- 2005-02-17 US US10/588,574 patent/US20070286916A1/en not_active Abandoned
- 2005-02-17 AU AU2005212150A patent/AU2005212150A1/en not_active Abandoned
- 2005-02-17 WO PCT/SE2005/000220 patent/WO2005077391A1/en active Application Filing
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WO2004103083A1 (en) * | 2003-05-22 | 2004-12-02 | Synbiotics Ab | A probiotic composition comprising at least two lactic acid bacterial strains which are able to colonise the gastrointestinal tracts in combination with having intestinal survival property, intestinal binding property, an infection protection property and a fiber fermenting property |
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Also Published As
Publication number | Publication date |
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AU2005212150A1 (en) | 2005-08-25 |
SE0400355D0 (en) | 2004-02-17 |
EP1715876A1 (en) | 2006-11-02 |
US20070286916A1 (en) | 2007-12-13 |
CA2555151A1 (en) | 2005-08-25 |
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