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WO1997020577A1 - Formulation therapeutique amelioree et procede correspondant - Google Patents

Formulation therapeutique amelioree et procede correspondant Download PDF

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Publication number
WO1997020577A1
WO1997020577A1 PCT/AU1996/000786 AU9600786W WO9720577A1 WO 1997020577 A1 WO1997020577 A1 WO 1997020577A1 AU 9600786 W AU9600786 W AU 9600786W WO 9720577 A1 WO9720577 A1 WO 9720577A1
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WO
WIPO (PCT)
Prior art keywords
antibody
probiotic
disease
animal
treatment
Prior art date
Application number
PCT/AU1996/000786
Other languages
English (en)
Inventor
David Spencer Chandler
Benjamin John Reed
Original Assignee
Pharma Pacific Pty. Ltd.
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
Application filed by Pharma Pacific Pty. Ltd. filed Critical Pharma Pacific Pty. Ltd.
Priority to AU76872/96A priority Critical patent/AU7687296A/en
Publication of WO1997020577A1 publication Critical patent/WO1997020577A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/40Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial

Definitions

  • This invention relates to a method and composition for treatment or prevention of disease.
  • Gastrointestinal disease is a significant cause of morbidity and mortality in humans and in domestic animals, particularly in the first few weeks of life.
  • a high proportion of hospital admissions of babies results from gastrointestinal infection, which leads to rapid dehydration, and may prove fatal.
  • gastrointestinal infection spreads extremely rapidly, and results in failure to thrive, often leading to death. The effects of these conditions are particularly devastating in the production of pigs, dairy calves and poultry.
  • ReSus a product designed for small weak piglets named ReSus is manufactured by Nufarm Limited. This product combines hyperimmune colostrum from dairy cows vaccinated against strains of E ⁇ cherichia coli that infect neonatal piglets in a high energy food base. Other products, available overseas, use im unoglobulins obtained from colostrum, milk, whey or plasma.
  • rotavirus diarrhoea it is known that the most important protective factor is the presence of specific antibody in the lumen of the small intestine. Protection against rotavirus diarrhoea can be achieved by oral administration of IgG, whether the IgG is homologous or heterologous (Snodgrass D.R.
  • Hyperimmune colostral antibodies directed against organisms causing gastrointestinal disease have been widely recognised to be effective in disease control (Tackett et al . , New England J. Med. 1988 318 1240-1243; Hilpert et al , J. Infect. Dis., 1987 156-158; Ebina et al, Med. Microbiol . Immunol., 1985 174-177; Davidson et al , Lancet, 1989, 23 September 709-712).
  • Orally-administered protease has also been shown to influence the potential for microbial colonisation of the small intestine by degrading receptors for microbial adhesins and toxins (Mynott et al, Infection and Immunity, 1991 59. 3708-3714, Chandler et al, 1994 Vet. Microbiol. 18:203-215) .
  • protease-cleaved antibody in order to prevent or alleviate gastrointestinal disease
  • International Patent Application No. PCT/AU94/00121 Pharma Pacific Pty.Ltd.
  • Administration of protease-cleaved antibody was considered particularly beneficial in neonates, where gastric and intestinal proteolytic activity is low because of developmental immaturity, (Moughan P.J. et al. In.
  • probiotics The main problem with the therapeutic function of probiotics is the difficulty in establishing these strains in the gastrointestinal tract (Cain, C.,1988. Observations of indigenous and non- indigenous lactic acid bacteria as potential probiotic organisms in pigs. M.Sc. Thesis, School of Agriculture, La Trobe University) .
  • the present invention provides a further and simpler means of improving the colonisation of the intestinal tract by probiotic strains, thereby extending the effectiveness and/or period of disease protection offered by oral administration of antibody. It also allows antibiotic use to be avoided where possible.
  • the present inventors have surprisingly found that administration to young animals of antibody in a substantially whole form, together with a probiotic organism gives high levels of protection against gastrointestinal disease. This is surprising since it was previously thought that it was necessary to subject the antibody to proteolytic digestion in order to obtain efficient prophylaxis or treatment of a disease. In addition, the inventors have also surprisingly found that use of substantially whole antibody and a probiotic organism provides a synergistic effect in the treatment of gastrointestinal disease.
  • the invention provides a method of treatment or prophylaxis of disease in an animal said method comprising administering effective amounts of substantially whole antibody and one or more strains of suitable probiotic organisms to said animal, wherein said animal is not naturally protected by exposure to appropriate or adequate antibody.
  • the method encompasses both treatment and prevention of disease.
  • the diseases which may be treated by the method are diseases of the alimentary tract, reproductive tract and include oral diseases, gastrointestinal diseases, vaginal diseases caused by the presence or colonisation of inappropriate or pathogenic microorganisms such as bacteria, viruses and fungi.
  • animal refers to any animal capable of treatment or prophylaxis by the method of invention such as mammals (Eg. hiI ans, domestic animals such as pigs, cattle, sheep, goats, horses, llamas, alpacas) and other animals such as poultry for example, chickens, geese, ducks and larger birds such as emus and ostriches and the like.
  • mammals Eg. hiI ans, domestic animals such as pigs, cattle, sheep, goats, horses, llamas, alpacas
  • other animals such as poultry for example, chickens, geese, ducks and larger birds such as emus and ostriches and the like.
  • the term "effective amounts” refers to the amounts of the antibody and one or more probiotic organisms required to effectively treat or prevent the disease.
  • substantially whole antibody refers to an antibody which has not been treated proteolytically or is not intentionally treated to degrade the antibody or to modify it to any degree.
  • the antibody suitable for use in the invention does not have to be purified, and may be derived from immune serum or colostrum, from egg yolk of immunised poultry or may be a monoclonal antibody or a bioengineered antibody.
  • the antibody of the invention is preferably an immunoprotective antibody which means that the antibody has specificity against the pathogenic agent of the disease targeted or against a toxin or other molecule produced by the pathogen which alone or in combination with a probiotic agent protects against the pathogenic effects of the causative organism of the disease.
  • Colostrum from immunised dairy animals, such as cows, sheep or goats is especially convenient for use in the invention.
  • the antibody may be IgG, IgA or igM, but is most preferably bovine igG j ⁇ and/or IgA.
  • Antibody from egg yolk (IgY) may also be used. It will be appreciated that one or more antibodies may be used.
  • the substantially whole antibody and one or more suitable probiotic organisms may be administered together, separately or sequentially to the animal. Most preferably the substantially whole antibody and one or more suitable probiotic organisms are administered together.
  • suitable in reference to the one or more strains of probiotic organisms means suitable for prophylaxis or treatment of the disease targeted.
  • the causative organisms and associated toxins of such diseases which may be treated or prevented include, but are not limited to, Escherichia coli, Clostridium difficile, Helicobacter pylori, Cryptosporidiv ⁇ species, Mycobacterium species, Candida species, Microsporidia species such as Af.paratuJber ⁇ ulosis and rotaviruses.
  • probiotic organism refers to any microorganism capable of imparting a beneficial effect on the animal when administered orally or by another route to such animal.
  • the probiotic organism is suitably an organism indigenous to the species of the animal to be treated, although it may be a non-indigenous member of the mucosal flora of healthy individuals of other species.
  • the probiotic organism includes, but is not limited to, a actobacillus, Bacillus, Streptococcus,
  • Probiotic strains may be selected on the basis of their ability to colonise effectively and to flourish on the infected surface, or potentially infected surface, to be treated. They may be strains that possess properties that are antagonistic toward the pathogen being displaced. Alternatively the probiotic organism may permit selective overgrowth in the host thereby precluding or excluding the pathogen.
  • the term "wherein said animal is not naturally protected by exposure to an appropriate or adequate antibody” refers to an animal which is not receiving appropriate antibody or adequate levels of such antibody from drinking mother's milk and other situations where the animal is not ingesting or otherwise producing appropriate or adequate endogenous antibody, such as in the case where the animal's immune system is functioning below its normal abilities or where the onset of the disease is acute and the host's immune system has not recently been exposed to the pathogen, such as traveller's diarrhoea in humans.
  • the method of the invention may be used in conjunction with other treatments, such as antibiotic treatment, or electrolyte therapy. Preferably antibiotic treatment is avoided unless absolutely necessary, in which case a probiotic with appropriate antibiotic resistance should be used.
  • the invention is specifically described with reference to gastrointestinal disease, it will be clearly understood that the invention is applicable to the treatment or prevention of disease at other sites which are subject to changes in flora during disease, such as the oral cavity and the vaginal tract.
  • the mode of administration will be chosen depending on the site of intended treatment. Modes of administration contemplated include lozenges or other tablets, pessaries, creams, lotions, washes and so on.
  • the methods of the invention are suitable for treatment of immunocompromised patients or patients particularly prone to infection, such as HIV-infected patients or patients with symptoms of AIDS-related complex or AIDS, or patients suffering from extensive burns or scalds, or for the treatment of patients suffering from gastrointestinal malabsorption syndromes or inflammatory bowel disease.
  • the methods of the invention are also suitable for treatment of patients receiving H 2 -receptor antagonists such as Zantac or Tagamet, or proton-pump inhibitors such as Losec, which inhibit acid secretion in the stomach, and have diarrhoea as a frequent side-effect.
  • H 2 -receptor antagonists such as Zantac or Tagamet
  • proton-pump inhibitors such as Losec
  • the invention provides a co ⁇ tposition for treatment or prevention of gastrointestinal disease in an animal, comprising a) an effective amount of substantially whole antibody, and b) an effective amount of one or more strains of suitable probiotic organisms, together with a pharmaceutically-acceptable carrier.
  • the formulation provides a multiple format, including antibody, probiotic and electrolytes useful to offset the losses induced by pathogen colonisation.
  • the formulation may comprise a multi-component tablet, optionally enteric coated or in the form of a suspension or granules for reconstitution, in which the probiotic and antibody are combined.
  • Conventional fillers, granulating agents, excipients may be present. Variations will be obvious to the person skilled in the art.
  • the invention also provides formulations for use in the aforesaid method. Individual formulations will depend upon the antibody and probiotic type, and can be devised using known formulation principles and normal trial-and-error experimentation.
  • liquid formulations including drops or sprays, or aerosol formulations may be particularly suitable.
  • Treatment and dosage regimen Treatments consisted of six twenty ml doses given to piglets at approximately 6h intervals. Piglets were taken from the sow at birth (before suckling from the sow) weighed and ear-tagged. Approximately weight-matched groups of piglets were allocated randomly to one of six following treatment groups as shown in Table 1.
  • Piglets in the colostrum replacer-treated groups received a commercial colostrum replacer designated as ReSus (Nufarm Animal Health) .
  • ReSus contains bovine colostrum from cows immunised against the E. coli types which infect piglets, using polyvalent whole cell and pilus-based vaccines.
  • Piglets in the antibody treatment groups received bovine colostral antibody from the same bulk batch of colostrum used in the manufacture of the ReSus batch referred to above, but in this case the antibody had been removed from the base colostrum by fat removal and acid precipitation of the casein. The antibody was then further purified by (NH 4 ) 2 S0 4 precipitation and dialysis against distilled water. (Fang, W.D.
  • Antibody-containing treatments were diluted with milk prior to use, such that they have an equivalent titre of blocking activity in an ELISA blocking assay to that of ReSus.
  • the blocking assay consisted of K88 + E. coli on the solid phase, followed by test antibody, anti-K88 enzyme conjugate and enzyme substrate.
  • Challenge doses consisted of a sheep blood agar lawn culture of haemolytic K88 + E. coli (strain WG, O149;K91;K88ac;H10, Tzipori et al, Aust. Vet. J., 1980 5_6 274) suspended in 2ml of sterile phosphate-buffered saline (PBS, 0.1M, pH 7.2). This dose consisted of approximately 5 x 10 9 cfu/dose.
  • PBS sterile phosphate-buffered saline
  • Probiotic treatments were prepared by suspending from Rogosa Agar a 48h anaerobic lawn culture of Lacto-acillus fermentum (strain 104, kindly supplied by Dr. P. Conway, Biotechnology Department, University of New South Wales) into each 20ml treatment dose of combined probiotic:antibody (ReSus or purified antibody), or milk replacer for piglets in the probiotic only treatment group.
  • Control piglets were given the same volume of commercial milk replacer at the same regimen as piglets given the probiotic and antibody-containing treatments.
  • Treatment doses, milk feeds and bacterial challenge doses were given by oro-gastric tube.
  • Piglets (56) born to six sows were used in the trials. After allocation to treatment groups piglets were transferred to heated cages, usually as pairs. Where bullying was a problem or odd numbers were available in the treatment group, piglets were housed individually. Piglets receiving treatments containing probiotic were housed and treated using facilities located on opposite sides of the cage room. At about two hours after birth the piglets were given their first treatment dose, followed thirty minutes later by a bacterial challenge dose.
  • Faecal scores 0. Normal soft damp to formed faeces or meconium.
  • SI small intestine
  • 1 means region 1
  • 2 means region 2
  • e3 means region 3.
  • LSD means least significant difference.
  • E. coli ilactobacillus ratio over antibody-only treatments at the stomach or mid-SI sites E. coli ilactobacillus ratio over antibody-only treatments at the stomach or mid-SI sites.
  • Table 7 Mean condition scores of piglets recorded immediately prior to post mortem examination (T) and 12h prior to death (T-12h) .
  • Table 8 Mean faecal scores of piglets recorded immediateley prior to post mortem examination (T) and 12h prior to death (T-12h) .
  • This experiment was designed to determine whether the high level of protection against bacterial challenge provided by combined antibody:probiotic treatments in the previous experiment could be extended to improved treatment of pre- existing diarrhoeal disease.
  • Colostrum-deprived piglets were allocated to six treatment groups, as outlined for Example 1.
  • piglets were given their first challenge dose at 2h after birth; however treatments were withheld until diarrhoea, indicated by a faecal score of > 2, had developed. This faecal score was generally observed within 2h of the onset of diarrhoea in untreated animals, and generally occurred between 12h and 18h after challenge.
  • Piglets were given a 20ml milk feed immediately prior to the challenge dose, and similar subsequent feeds were given at approximately 2.5h intervals. Piglets were inspected approximately hourly. Where necessary rectal swabs were taken to facilitate reading faecal scores. Once treatments were commenced they replaced milk feeds.
  • Piglets born to two sows were assessed.
  • Piglet numbers for each treatment were: Control, 5; Ab, 4; Res, 2; prob, 4; ResProb, 2; AbProb, 4.
  • Piglets were housed as described for Example 1. Probiotic- treated animals were again segregated and treated using separate equipment, and appropriate care was used to minimise the likelihood of cross-contamination. Piglets were killed approximately lh after their 6th treatment.
  • Colonisation of the intestines by lactobacilli in piglets infected by E. colx at commencement of treatment was comparable at post mortem examination to that found in piglets where the treatments were used therapeutically. Generally piglets with higher levels of colonisation were healthier, with the exception of piglets treated with probiotic alone.
  • Table 15 Mean faecal scores of piglets at post mortem examination and 8h prior to death (T-8h) .
  • Purified clostral antibody is derived by hyper immunization of dairy cows with a protective immunogen from the target pathogen. Immediately after parturition cows are milked twice daily until about 10-20 1 of colostrum have been collected from each cow. This colostrum is stored frozen until required for processing. Colostral antibody is then prepared by use of a commercial separator or centrifuge to remove the fat component. The skim colostrum is then treated by ammonium sulphate precipitation and dialysis against distilled water to obtain a fraction containing principally IgG (Fang, W. D. and Mukkur, T.K.S. Biochem J., 1976 155 25).
  • affinity chromatography or other purification techniques could be employed to obtain a desired level of antibody purification. If payload (weight of antibody required for a suitable dose volume) or palatability/physical appearance is not a problem (e.g. treating larger animals such as calves), skim colostrum could be used directly. When treating gastrointestinal diseases with colostral antibody it is generally desirable to remove the fat. Additional purification to a predominantly antibody fraction helps remove undesirable smells and blood and cellular contamination that may be associated with peripartum lactation.
  • the antibody is conveniently stored and processed in a dry form, following freeze drying or spray drying at low temperature, for example, in a multi-stage drier.
  • purified colostral antibody at a dose rate shown to be effective in treating the disease syndrome (such as approximately 12.5mg/kg body weight in this case) is admixed with an appropriate probiotic, also at a dose rate shown effective (such as approximately 10 9 cfu lactobacillus fermentum strain 104/ lOOmg tablet) and following addition of appropriate fillers and binding agents, compressed into tablet form.
  • an appropriate probiotic such as approximately 10 9 cfu lactobacillus fermentum strain 104/ lOOmg tablet
  • these tablets are preferably dissolved in warm water or milk, prior to dosing with a feeding bottle or by orogastric tube.
  • a tablet for adult animal or human treatment may optionally include traditional enteric coating technologies or a buffered liquid delivery to improve protein or microbiological persistence, in the gastric environment. Delivery is obviously not limited to combined treatment via tablet, but may be separate tablets or powders separate or combined capsules, granules (macro or micro) or gel formulations.

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  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Mycology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention se rapporte à un procédé de traitement ou de prophylaxie d'une maladie chez un animal, qui consiste à administrer audit animal des quantités efficaces d'anticorps sensiblement 'entier' et au moins une souche d'organismes probiotiques appropriés.
PCT/AU1996/000786 1995-12-06 1996-12-05 Formulation therapeutique amelioree et procede correspondant WO1997020577A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU76872/96A AU7687296A (en) 1995-12-06 1996-12-05 Improved therapeutic formulation and method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPN6984 1995-12-06
AUPN6984A AUPN698495A0 (en) 1995-12-06 1995-12-06 Improved therapeutic formulation and method

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US6080401A (en) * 1998-11-19 2000-06-27 Reddy; Malireddy S. Herbal and pharmaceutical drugs enhanced with probiotics
US6346422B1 (en) * 1998-04-30 2002-02-12 Ceva Sante Animale Method of selecting bacterial strains
WO2002005829A3 (fr) * 2000-07-17 2002-05-02 Hansens Lab Procede permettant de reduire les changements dans la flore gastro-intestinale nuisibles du point de vue ecologique intervenus chez des patients suivant un traitement medicamenteux
EP1100950A4 (fr) * 1998-07-30 2002-10-16 Wisconsin Alumni Res Found Usines d'anticorps bacteriens gastro-intestinaux
JP2004501095A (ja) * 2000-05-11 2004-01-15 アンスティテュ ナショナール ド ラ ルシェルシュ アグロノミク 消化器系障害の予防または治療のための水素依存性酢酸生成株の使用
WO2005005481A3 (fr) * 2003-07-10 2005-04-28 Avitek Pharma Inc Therapie combinatoire pour maladies gastro-enteriques provoquees par des micro-organismes
EP1409010A4 (fr) * 2000-07-03 2005-06-29 Probendo Pty Ltd Traitement de l'endotoxemie et des troubles associes par des probiotiques
US7785635B1 (en) 2003-12-19 2010-08-31 The Procter & Gamble Company Methods of use of probiotic lactobacilli for companion animals
US7906112B2 (en) 2003-12-19 2011-03-15 The Procter & Gamble Company Canine probiotic Lactobacilli
EP2318047A1 (fr) 2008-06-24 2011-05-11 Nestec S.A. Probiotiques, iga sécrétoires et inflammation
EP2318046A1 (fr) 2008-06-24 2011-05-11 Nestec S.A. Probiotiques, iga sécrétoires et inflammation
US7998473B2 (en) 2003-12-19 2011-08-16 The Procter & Gamble Company Methods of treatment or prevention of gastrointestinal disorders using canine probiotic bifidobacterium
US8034601B2 (en) 2005-05-31 2011-10-11 The Procter & Gamble Company Feline probiotic bifidobacteria
US20120177650A1 (en) * 2009-09-23 2012-07-12 Borody Thomas J Therapy for enteric infections
US8563522B2 (en) 1997-07-08 2013-10-22 The Iams Company Method of maintaining and/or attenuating a decline in quality of life
US8809035B2 (en) 2003-12-19 2014-08-19 The Iams Company Canine probiotic Bifidobacterium
US8877178B2 (en) 2003-12-19 2014-11-04 The Iams Company Methods of use of probiotic bifidobacteria for companion animals
US9192177B2 (en) 2005-05-31 2015-11-24 The Iams Company Feline probiotic Lactobacilli
US9415083B2 (en) 2004-05-10 2016-08-16 Mars, Incorporated Method for decreasing inflammation and stress in a mammal
US9771199B2 (en) 2008-07-07 2017-09-26 Mars, Incorporated Probiotic supplement, process for making, and packaging
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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU8240687A (en) * 1986-12-12 1988-06-16 Biorem C.C. Preparation suitable for use in the treatment of enteric disorders
AU3836489A (en) * 1988-06-09 1990-01-05 Whitecliffe Laboratories Limited Treatment of immunodeficiency
AU5157790A (en) * 1989-02-15 1990-09-05 Eva Elisabeth Grahn A pharmaceutical preparation in the treatment of tonsillitis
AU5254790A (en) * 1989-04-06 1990-10-11 Chugai Seiyaku Kabushiki Kaisha Process for preparing a therapeutic agent for rotavirus infection
AU2920592A (en) * 1991-11-15 1993-06-15 Andrew Watt Bruce Lactobacillus and skim milk compositions and methods for preventing microbial urogenital infections
AU4158893A (en) * 1992-07-06 1994-01-13 Societe Des Produits Nestle S.A. Antigastritis agent
AU3736593A (en) * 1992-07-29 1994-03-03 United States Department Of Agriculture Probiotic for control of salmonella
AU7465794A (en) * 1993-09-06 1995-03-27 Zeneca Limited Probiotics
AU2613995A (en) * 1994-05-26 1995-12-21 Dibra S.P.A. Lactobacillus strains of human origin, their compositions and uses thereof

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU8240687A (en) * 1986-12-12 1988-06-16 Biorem C.C. Preparation suitable for use in the treatment of enteric disorders
AU3836489A (en) * 1988-06-09 1990-01-05 Whitecliffe Laboratories Limited Treatment of immunodeficiency
AU5157790A (en) * 1989-02-15 1990-09-05 Eva Elisabeth Grahn A pharmaceutical preparation in the treatment of tonsillitis
AU5254790A (en) * 1989-04-06 1990-10-11 Chugai Seiyaku Kabushiki Kaisha Process for preparing a therapeutic agent for rotavirus infection
AU2920592A (en) * 1991-11-15 1993-06-15 Andrew Watt Bruce Lactobacillus and skim milk compositions and methods for preventing microbial urogenital infections
AU4158893A (en) * 1992-07-06 1994-01-13 Societe Des Produits Nestle S.A. Antigastritis agent
AU3736593A (en) * 1992-07-29 1994-03-03 United States Department Of Agriculture Probiotic for control of salmonella
AU7465794A (en) * 1993-09-06 1995-03-27 Zeneca Limited Probiotics
AU2613995A (en) * 1994-05-26 1995-12-21 Dibra S.P.A. Lactobacillus strains of human origin, their compositions and uses thereof

Cited By (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8563522B2 (en) 1997-07-08 2013-10-22 The Iams Company Method of maintaining and/or attenuating a decline in quality of life
US6346422B1 (en) * 1998-04-30 2002-02-12 Ceva Sante Animale Method of selecting bacterial strains
EP1100950A4 (fr) * 1998-07-30 2002-10-16 Wisconsin Alumni Res Found Usines d'anticorps bacteriens gastro-intestinaux
US6080401A (en) * 1998-11-19 2000-06-27 Reddy; Malireddy S. Herbal and pharmaceutical drugs enhanced with probiotics
JP2004501095A (ja) * 2000-05-11 2004-01-15 アンスティテュ ナショナール ド ラ ルシェルシュ アグロノミク 消化器系障害の予防または治療のための水素依存性酢酸生成株の使用
US7749494B2 (en) 2000-05-11 2010-07-06 Institut National De La Recherche Agronomique Use of hydrogenotrophic acetogenic strains for preventing or treating digestive disorders
EP1409010A4 (fr) * 2000-07-03 2005-06-29 Probendo Pty Ltd Traitement de l'endotoxemie et des troubles associes par des probiotiques
WO2002005829A3 (fr) * 2000-07-17 2002-05-02 Hansens Lab Procede permettant de reduire les changements dans la flore gastro-intestinale nuisibles du point de vue ecologique intervenus chez des patients suivant un traitement medicamenteux
WO2005005481A3 (fr) * 2003-07-10 2005-04-28 Avitek Pharma Inc Therapie combinatoire pour maladies gastro-enteriques provoquees par des micro-organismes
US8900568B2 (en) 2003-12-19 2014-12-02 The Iams Company Method of treating diarrhea in a canine
US8894991B2 (en) 2003-12-19 2014-11-25 The Iams Company Canine probiotic Lactobacilli
US9580680B2 (en) 2003-12-19 2017-02-28 Mars, Incorporated Canine probiotic bifidobacterium pseudolongum
US8809035B2 (en) 2003-12-19 2014-08-19 The Iams Company Canine probiotic Bifidobacterium
US7998473B2 (en) 2003-12-19 2011-08-16 The Procter & Gamble Company Methods of treatment or prevention of gastrointestinal disorders using canine probiotic bifidobacterium
US8802158B2 (en) 2003-12-19 2014-08-12 The Iams Company Methods of use of probiotic Lactobacilli for companion animals
US8877178B2 (en) 2003-12-19 2014-11-04 The Iams Company Methods of use of probiotic bifidobacteria for companion animals
US8840880B2 (en) 2003-12-19 2014-09-23 The Iams Company Canine probiotic bifidobacteria globosum
US7785635B1 (en) 2003-12-19 2010-08-31 The Procter & Gamble Company Methods of use of probiotic lactobacilli for companion animals
US9821015B2 (en) 2003-12-19 2017-11-21 Mars, Incorporated Methods of use of probiotic bifidobacteria for companion animals
US8900569B2 (en) 2003-12-19 2014-12-02 The Iams Company Method of treating diarrhea in a canine
US7906112B2 (en) 2003-12-19 2011-03-15 The Procter & Gamble Company Canine probiotic Lactobacilli
US9415083B2 (en) 2004-05-10 2016-08-16 Mars, Incorporated Method for decreasing inflammation and stress in a mammal
US9192177B2 (en) 2005-05-31 2015-11-24 The Iams Company Feline probiotic Lactobacilli
US8034601B2 (en) 2005-05-31 2011-10-11 The Procter & Gamble Company Feline probiotic bifidobacteria
US9404162B2 (en) 2005-05-31 2016-08-02 Mars, Incorporated Feline probiotic bifidobacteria and methods
US9427000B2 (en) 2005-05-31 2016-08-30 Mars, Incorporated Feline probiotic lactobacilli composition and methods
AU2009264417B2 (en) * 2008-06-24 2015-04-30 Société des Produits Nestlé S.A. Probiotics, secretory IgA and inflammation
CN102076360A (zh) * 2008-06-24 2011-05-25 雀巢产品技术援助有限公司 益生菌、分泌型免疫球蛋白a和炎症
EP2700411A1 (fr) * 2008-06-24 2014-02-26 Nestec S.A. Probiotiques, igA sécrétoire et infection
US9822167B2 (en) 2008-06-24 2017-11-21 Nestec S.A. Probiotics, secretory IgA and inflammation
US10501530B2 (en) 2008-06-24 2019-12-10 Societe Des Produits Nestle S.A. Probiotics, secretory IgA and inflammation
EP2318047A1 (fr) 2008-06-24 2011-05-11 Nestec S.A. Probiotiques, iga sécrétoires et inflammation
US9173937B2 (en) 2008-06-24 2015-11-03 Nestec S.A. Probiotics, secretory IgA and infection
US9629908B2 (en) 2008-06-24 2017-04-25 Nestec S.A. Probiotics, secretory IgA and infection
JP2011525483A (ja) * 2008-06-24 2011-09-22 ネステク ソシエテ アノニム プロバイオティクス、分泌型IgA及び炎症
JP2011525484A (ja) * 2008-06-24 2011-09-22 ネステク ソシエテ アノニム プロバイオティクス、分泌型IgA及び感染症
EP2700412A1 (fr) * 2008-06-24 2014-02-26 Nestec S.A. Probiotiques, igA sécrétoire et inflammation
EP2318046A1 (fr) 2008-06-24 2011-05-11 Nestec S.A. Probiotiques, iga sécrétoires et inflammation
US10709156B2 (en) 2008-07-07 2020-07-14 Mars, Incorporated Pet supplement and methods of making
US9771199B2 (en) 2008-07-07 2017-09-26 Mars, Incorporated Probiotic supplement, process for making, and packaging
US10104903B2 (en) 2009-07-31 2018-10-23 Mars, Incorporated Animal food and its appearance
US20120177650A1 (en) * 2009-09-23 2012-07-12 Borody Thomas J Therapy for enteric infections
CN102711819A (zh) * 2009-09-23 2012-10-03 托马斯·朱利叶斯·波洛迪 肠道感染疗法
EP2480255A4 (fr) * 2009-09-23 2013-03-20 Borody Thomas J Thérapie pour infections entériques
JP2013505289A (ja) * 2009-09-23 2013-02-14 トーマス・ジュリアス・ボロディ 腸管感染症の治療法
US11013773B2 (en) 2011-07-14 2021-05-25 4D Pharma Research Limited Lactic acid bacterial strains
US11266698B2 (en) 2011-10-07 2022-03-08 4D Pharma Research Limited Bacterium for use as a probiotic for nutritional and medical applications
US11414463B2 (en) 2013-04-10 2022-08-16 4D Pharma Research Limited Polypeptide and immune modulation
US10851137B2 (en) 2013-04-10 2020-12-01 4D Pharma Research Limited Polypeptide and immune modulation
US10973872B2 (en) 2014-12-23 2021-04-13 4D Pharma Research Limited Pirin polypeptide and immune modulation
US11723933B2 (en) 2014-12-23 2023-08-15 Cj Bioscience, Inc. Composition of bacteroides thetaiotaomicron for immune modulation
US10456444B2 (en) 2014-12-23 2019-10-29 4D Pharma Research Limited Pirin polypeptide and immune modulation
US10391130B2 (en) 2015-06-15 2019-08-27 4D Pharma Research Limited Compositions comprising bacterial strains
US10780134B2 (en) 2015-06-15 2020-09-22 4D Pharma Research Limited Compositions comprising bacterial strains
US10493112B2 (en) 2015-06-15 2019-12-03 4D Pharma Research Limited Compositions comprising bacterial strains
US10500237B2 (en) 2015-06-15 2019-12-10 4D Pharma Research Limited Compositions comprising bacterial strains
US11433106B2 (en) 2015-06-15 2022-09-06 4D Pharma Research Limited Compositions comprising bacterial strains
US11273185B2 (en) 2015-06-15 2022-03-15 4D Pharma Research Limited Compositions comprising bacterial strains
US10864236B2 (en) 2015-06-15 2020-12-15 4D Pharma Research Limited Compositions comprising bacterial strains
US11389493B2 (en) 2015-06-15 2022-07-19 4D Pharma Research Limited Compositions comprising bacterial strains
US11040075B2 (en) 2015-06-15 2021-06-22 4D Pharma Research Limited Compositions comprising bacterial strains
US11331352B2 (en) 2015-06-15 2022-05-17 4D Pharma Research Limited Compositions comprising bacterial strains
US10322151B2 (en) 2015-06-15 2019-06-18 4D Pharma Research Limited Compositions comprising bacterial strains
US10736926B2 (en) 2015-06-15 2020-08-11 4D Pharma Research Limited Compositions comprising bacterial strains
US10744167B2 (en) 2015-06-15 2020-08-18 4D Pharma Research Limited Compositions comprising bacterial strains
US10610550B2 (en) 2015-11-20 2020-04-07 4D Pharma Research Limited Compositions comprising bacterial strains
US11058732B2 (en) 2015-11-20 2021-07-13 4D Pharma Research Limited Compositions comprising bacterial strains
US10471108B2 (en) 2015-11-20 2019-11-12 4D Pharma Research Limited Compositions comprising bacterial strains
US10744166B2 (en) 2015-11-23 2020-08-18 4D Pharma Research Limited Compositions comprising bacterial strains
US10391128B2 (en) 2015-11-23 2019-08-27 4D Pharma Research Limited Compositions comprising bacterial strains
US10086023B2 (en) 2016-03-04 2018-10-02 4D Pharma Plc Compositions comprising bacterial strains
US10583158B2 (en) 2016-03-04 2020-03-10 4D Pharma Plc Compositions comprising bacterial strains
US10086022B2 (en) 2016-03-04 2018-10-02 4D Pharma Plc Compositions comprising bacterial strains
US10610549B2 (en) 2016-07-13 2020-04-07 4D Pharma Plc Composition comprising bacterial strains
US11224620B2 (en) 2016-07-13 2022-01-18 4D Pharma Plc Compositions comprising bacterial strains
US10080772B2 (en) 2016-07-13 2018-09-25 4D Pharma Plc Compositions comprising bacterial strains
US10967010B2 (en) 2016-07-13 2021-04-06 4D Pharma Plc Compositions comprising bacterial strains
US10610548B2 (en) 2016-07-13 2020-04-07 4D Pharma Plc Compositions comprising bacterial strains
US10960031B2 (en) 2016-07-13 2021-03-30 4D Pharma Plc Compositions comprising bacterial strains
US10086020B2 (en) 2016-07-13 2018-10-02 4D Pharma Plc Compositions comprising bacterial strains
US10086021B2 (en) 2016-12-12 2018-10-02 4D Pharma Plc Compositions comprising bacterial strains
US10543238B2 (en) 2016-12-12 2020-01-28 4D Pharma Plc Compositions comprising bacterial strains
US10485830B2 (en) 2016-12-12 2019-11-26 4D Pharma Plc Compositions comprising bacterial strains
US10898526B2 (en) 2016-12-12 2021-01-26 4D Pharma Plc Compositions comprising bacterial strains
US11376284B2 (en) 2017-05-22 2022-07-05 4D Pharma Research Limited Compositions comprising bacterial strains
US11382936B2 (en) 2017-05-22 2022-07-12 4D Pharma Research Limited Compositions comprising bacterial strains
US11123378B2 (en) 2017-05-22 2021-09-21 4D Pharma Research Limited Compositions comprising bacterial strains
US10987387B2 (en) 2017-05-24 2021-04-27 4D Pharma Research Limited Compositions comprising bacterial strain
US11007233B2 (en) 2017-06-14 2021-05-18 4D Pharma Research Limited Compositions comprising a bacterial strain of the genus Megasphera and uses thereof
US11123379B2 (en) 2017-06-14 2021-09-21 4D Pharma Research Limited Compositions comprising bacterial strains
US11660319B2 (en) 2017-06-14 2023-05-30 4D Pharma Research Limited Compositions comprising bacterial strains
US11779613B2 (en) 2017-06-14 2023-10-10 Cj Bioscience, Inc. Compositions comprising a bacterial strain of the genus Megasphera and uses thereof
US12048720B2 (en) 2017-06-14 2024-07-30 Cj Bioscience, Inc. Compositions comprising bacterial strains

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