WO2011033310A1 - Flore intestinale encapsulée extraite de fèces destinée à être utilisée dans le traitement de troubles gastro-intestinaux - Google Patents

Flore intestinale encapsulée extraite de fèces destinée à être utilisée dans le traitement de troubles gastro-intestinaux Download PDF

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Publication number
WO2011033310A1
WO2011033310A1 PCT/GB2010/051561 GB2010051561W WO2011033310A1 WO 2011033310 A1 WO2011033310 A1 WO 2011033310A1 GB 2010051561 W GB2010051561 W GB 2010051561W WO 2011033310 A1 WO2011033310 A1 WO 2011033310A1
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Prior art keywords
extract
flora
digestive tract
medicaments
treatment
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PCT/GB2010/051561
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English (en)
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William John Martin
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William John Martin
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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37—Digestive system
    • A61K35/38—Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to medicaments for the prevention and/or treatment of nosocomial infections, and methods of manufacturing such medicaments.
  • the invention also relates to methods of preventing and/or treating nosocomial infections.
  • the medicaments and methods are particularly suited to the treatment of nosocomial infections causing diarrhoea and to the rehabilitation of iatrogenic degraded intestinal flora.
  • Iatrogenic diseases and nosocomial infections constitute a significant cause of distress and morbidity amongst patients in hospitals or other care facilities.
  • Clostridium Difficile (C. Difficile) is one of the major infectious organisms associated with the development of nosocomial infections. In recent years, the incidences of such infection have risen by around 850% in England and Wales, and C. Difficile infections are calculated to have cost 26,208 lives in these territories in the period from 1997 to 2007. In a US study the rate of C. difficile acquisition was estimated to be 13% in patients with hospital stays of up to 2 weeks and 50% in those with hospital stays longer than 4 weeks. Patients who share a room with a C. difficile-positive patient acquire the organism after an estimated hospital stay of 3.2 days, as compared with a hospital stay of 18.9 days for other patients. [Reed and Kemmerly (2009) The Ochsner Journal 9:27-31].
  • C. Difficile Normally the proliferation of C. Difficile within the digestive tract is prevented by the presence of other anaerobic bacteria that compete for the same environmental niche. However, in cases where the natural composition of the digestive tract flora is disrupted, for instance by antibiotic treatment, chemotherapy or radiotherapy, then the C. Difficile may be able to proliferate without competition. In such cases infection by C. Difficile may give rise to diseases including colitis, toxic megacolon and diarrhoea. Diarrhoea of this sort can be very severe, and can pose a threat to the life of those suffering from this condition.
  • faecal transplant therapy One method that has been reported to be highly effective in the treatment of nosocomial infections, such C. Difficile infections causing diarrhoea, is faecal transplant therapy.
  • this treatment (which was first reported in 1958) faecal material from a donor is administered to the digestive tract of a patient suffering from a nosocomial infection.
  • the faecal sample includes constituents (such as bacterial constituents) representative of the digestive tract flora in the donor. These constituents are able to replicate within the digestive tract of the recipient, and thus restore the normal flora and eliminate the infection.
  • Treatments have been reported in which faecal samples have been administered by means of enema, colonoscope, catheter or nasoenteral tube (suitable delivery means being selected depending on the site to which the sample is to be administered). Such treatments have been reported to have a success rate of between 90 and 95%.
  • a first aspect of the invention there is provided the use of an extract representative of the flora of the digestive tract in the manufacture of an encapsulated medicament for the prevention and/or treatment of iatrogenic disease of the digestive tract.
  • This first aspect of the invention also provides an extract representative of the flora of the digestive tract for use as an encapsulated medicament for the prevention and/or treatment of iatrogenic disease of the digestive tract.
  • an extract representative of the flora of the digestive tract in the manufacture of an encapsulated medicament for the prevention and/or treatment of nosocomial infections of the digestive tract.
  • This second aspect of the invention also provides an extract representative of the flora of the digestive tract for use as an encapsulated medicament for the prevention and/or treatment of nosocomial infections of the digestive tract.
  • the medicaments manufactured in accordance with these aspects of the invention, or using extracts in the manner described in these aspects, may be referred to as medicaments of the invention.
  • a method of preventing and/or treating iatrogenic diseases of the digestive tract comprising administering to a patient in need of such prevention and/or treatment an encapsulated extract representative of the flora of the digestive tract.
  • a method of preventing and/or treating nosocomial infections of the digestive tract comprising administering to a patient in need of such prevention and/or treatment an encapsulated extract representative of the flora of the digestive tract.
  • Iatrogenic diseases are diseases occurring as a result of medical treatment. Such treatments may include the use of medicinal agents, or surgical techniques. Examples of iatrogenic diseases that may be prevented or treated using the medicaments or methods of the invention are considered in more detail below.
  • Nosocomial infections are infections acquired in a hospital or other healthcare environment, and are secondary to a patient's original condition.
  • An infection may be classified as nosocomial if it first appears 48 hours or more after admission to the hospital or healthcare environment, or within 30 days after discharge of the patient. Examples of nosocomial infections that may be prevented or treated using the medicaments or methods of the invention are considered in more detail below.
  • the present invention is based upon the inventor's finding that extracts that are representative of the flora of the digestive tract, and that contain constituents-able to reproduce within the digestive tract and establish a beneficial flora, can be encapsulated to produce medicaments that are able to prevent or treat both iatrogenic diseases and nosocomial infections.
  • the medicaments of the invention may take the form of prepared medicaments in which a suitable extract is encapsulated.
  • Such encapsulated medicaments may be provided in dosage form. It will be appreciated that one or more of such dosage forms may be used to provide a therapeutically effective amount of the extract (as considered elsewhere in the specification) to a patient.
  • a dosage unit may provide approximately 2-4 grams of dried extract, and preferably approximately 2.5 grams of such an extract.
  • the extract may be prepared from an amount of around 20-200 grams of an initial sample representative of the flora of the digestive tract (such as a stool sample), and more preferably prepared from an amount of around 30-150 grams of such a sample.
  • encapsulated or term "encapsulated medicament” as used in the context of the present invention should be taken to mean that the extract is enclosed within a barrier that may subsequently be degraded to allow release of the extract.
  • encapsulated medicaments in accordance with the invention may be taken as encompassing any medicament in which the extract is provided within a degradable barrier, including (but not limited to) medicaments in which the extract is contained within a gelatine capsule, or medicaments in which the extract is provided within a coated table, or medicaments in which the extract is microencapsulated.
  • encapsulation include single-piece gel encapsulation and two piece gel encapsulation.
  • the medicaments of the invention are for oral administration to a patient, they may preferably be formulated in a manner in which the extract is protected from the conditions found in the upper reaches of the digestive tract, for example the stomach. In these areas of the digestive tract high acidity and the presence of digestive enzymes may otherwise damage the bacteria present in the extract. It is important that these bacteria should be maintained in a viable form, in order that they can exert their beneficial effect. Accordingly, it may be preferred that medicaments of the invention are formulated comprising an enteric coating. Such a coating does not significantly degrade in the upper reaches of the digestive tract and allows the bacteria within the extract to be released in a patient's intestines, and the bacteria are thus able to colonise this compartment of the digestive tract.
  • the enteric coating may be any such coating known to those of ordinary skill in the art.
  • Non-limiting examples of such coatings include Eudragit SIOO (Evonik Rohm GmbH, Darmstadt, Germany), cellulose acetate phthalate (CAP), a methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, polyvinyl acetate phthalate (PVAP), or a methyl methacrylate-methacrylic acid copolymer.
  • the coating includes Eudragit SIOO.
  • the coating may include a mixture of one or more of Eudragit SIOO, cellulose acetate phthalate (CAP), a methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, polyvinyl acetate phthalate (PVAP), and a methyl methacrylate-methacrylic acid copolymer.
  • CAP cellulose acetate phthalate
  • PVAP polyvinyl acetate phthalate
  • enteric coating examples include: cellulose acetate phthalate (CAP), methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP), methyl methacrylate-methacrylic acid copolymers and sodium alginate and stearic acid.
  • CAP cellulose acetate phthalate
  • PVAP polyvinyl acetate phthalate
  • a suitable barrier for use to encapsulate extracts, and thus to manufacture the medicaments of the invention may be one that degrades at a predetermined location in the digestive tract.
  • the medicaments of the invention may be encapsulated using a barrier that will degrade, and thus release the extract, after approximately four hours in the digestive tract (enteric coatings do not dissolve in acid conditions, such as the stomach, but dissolve in the more alkaline conditions of the small and large intestine).
  • the medicaments of the invention may be encapsulated using a barrier that will degrade, and thus release the extract, after passing approximately two metres through the digestive tract
  • One way in which the site at which an encapsulated medicament releases the extract may be determined is by the incorporation or attachment of RFID (radio frequency identification) tags in or to the barrier material.
  • a first signal generated when the tags are close to each other (and so associated with an intact encapsulated medicament) may be distinguished from a second signal generated when the tags are relatively further from one another (indicating that the encapsulated medicament has degraded, allowing the tags to drift apart).
  • the time and location of the degradation of the capsule may be determined by the generation of the second signal.
  • the use of RFID tags of this sort in the manufacture of the medicament of the invention can also provide other advantages, as considered further below.
  • an "extract" should be taken as excluding a sample taken from the digestive tract in its natural form.
  • An extract may be produced by processing such samples, for example to dry and/or enrich the bacteria present in the sample. Examples of suitable processing methods by which extracts may be derived from samples, such as faecal samples, are described elsewhere in the specification.
  • Extracts suitable for use in accordance with the invention will comprise bacteria that are representative of the flora of the digestive tract. Such extracts may optionally further comprise probiotic substances from the digestive tract, such as lactobacilli and bifidobacteria. Extracts representative of the flora of the digestive tract suitable for use in the medicaments or methods of the invention will be capable, on administration to a patient, of generating or maintaining, within the patient, a digestive tract flora that is not associated with iatrogenic disease, nosocomial infection, or diarrhoea. Such extracts may preferably contain elements which are able to counter C. difficile infection, for example, such extracts may optionally further comprise narrow spectrum antimicrobials which target unwanted bacteria such as C.
  • thuricin CD examples include thuricin CD.
  • thuricin CD examples include thuricin CD.
  • the medicaments or methods of the invention will utilise a therapeutically effective amount of such an extract.
  • a therapeutically effective amount of an extract will be an amount sufficient to allow the generation or maintenance of a digestive tract flora that is not associated with nosocomial infection or diarrhoea.
  • Such a suitable therapeutically effective amount may contain a therapeutically effective quantity of elements able to control or counter C. difficile infection.
  • This beneficial digestive tract flora may be established through colonisation of the digestive tract, and in particular the intestines and colon, by bacteria present in the extract.
  • a suitable extract may preferably comprise such bacteria in an amount sufficient to "saturate" the intestines of a patient to whom it is administered (i.e. to provide sufficient of the beneficial bacteria present in the extract that pathogenic bacteria are not able to establish or maintain themselves in sufficient quantities to cause nosocomial infection or diarrhoea).
  • the medicaments or methods of the invention may be used in the prevention and/or treatment of iatrogenic diseases caused by: antibiotic treatment, immunosuppressive therapy, radiotherapy, chemotherapy, or therapy with proton pump inhibitors.
  • iatrogenic diseases of the digestive tract include: iatrogenic C. difficile infections; iatrogenic Candida infections; and iatrogenic diarrhoea. These examples represent diseases that may be prevented or treated in preferred embodiments of the medicaments or methods of the invention. It may be particularly preferred that the medicaments or methods of the invention be used in the prevention or treatment of iatrogenic diarrhoea (for example as a result of antibiotic treatment, immunosuppressive therapy, radiotherapy, chemotherapy, or therapy with proton pump inhibitors).
  • the nosocomial infection that is to be prevented and/or treated by the methods of the invention is an infection causing nosocomial diarrhoea.
  • the medicaments or methods of the invention may also be used in the prevention and/or treatment of other conditions associated with nosocomial infections such as colitis; toxic megacolon; and thrush.
  • the medicaments or methods of the invention may be used in the prevention or treatment of nosocomial infections of the digestive tract including: Clostridium difficile infections; Candida (such as Candida albicans) infections which may result in "thrush".
  • aBMT allogeneic bone marrow transplantation
  • GvHD graft versus host disease
  • the medicaments are for oral administration.
  • Forms of encapsulated medicaments that are suitable for oral administration will be apparent to those skilled in the art, and these may be utilised in the manufacture of medicaments of the invention.
  • enteral administration is preferably by means of oral administration, but should also be taken as encompassing other forms of administration such as by suppository or the like.
  • medicaments of the invention are administered by routes other than orally this may limit the extent to which they can access the various compartments of the digestive tract, and thus limit the medicaments' effectiveness.
  • medicaments of the invention are administered anally (e.g.
  • the presence of the splenic flexure, cecocolic junction or ileocecal valve may prevent provision of the encapsulated extract to compartments "upstream" of these structures (such as the small intestine) which may allow nosocomial infection to become established (or remain established) in these compartments.
  • the extract is representative of the flora of the digestive tract of a patient to whom the medicament is to be administered.
  • Such extracts may be derived from samples, such as faecal samples, collected from such a patient.
  • the sample from which the extract is to be derived should preferably be collected prior to the development of any nosocomial infection, so that it is representative of the healthy digestive tract flora of the patient.
  • Such samples may, for example, be collected on entry of an individual into hospital or prior to their arrival in hospital. In the event that samples are collected prior to arrival at hospital then this may provide an opportunity for preparation of the medicaments, and subsequent use of the medicaments for prevention or treatment of a disease, to commence at the earliest possible opportunity.
  • autologous samples provide a number of advantages.
  • One such advantage is that there is no need to screen the sample for the presence of infective agents (such as viruses or other pathogens). If allogeneic samples are to be used such screens may be preferred in order to avoid the risk of transmission of infections from the donor patient or patients (from whom the extract is derived) to the recipient patient (to whom the extract is provided in a medicament or method of the invention). It will be appreciated that such screening may be time consuming and costly, and thus the use of autologous samples provides advantages in terms of increased safety, decreased time of production, and decreased cost. Furthermore, the use of autologous samples to produce extracts for use in the medicaments or methods of the invention may generally reduce the perceived distastefulness of such medicaments or methods to a prospective patient.
  • Examples of such circumstances include situations in which it is desired to produce large amounts of medicaments of the invention, for example in order to allow treatment of an infection afflicting many individuals.
  • the need to produce large amounts of the medicaments in a relatively short time may override the advantages associated with the use of autologous samples.
  • the donors from whom such allogeneic samples and extracts may be derived should be thoroughly screened in order to avoid the risk of transmission of infectious agents to patients receiving treatment with the medicaments or methods of the invention.
  • the digestive system flora present in such samples may then be expanded in order to allow the production of sufficient extract to provide medicaments for multiple patients.
  • the medicaments or methods of the invention will make use of extracts that are fully or partially dried.
  • the use of dried extracts provides a number of advantages, including reducing the volume of the extract that is to be administered, and improved acceptability to patients.
  • dried extracts will not dissolve the gels which may be employed for encapsulation.
  • the extract to be used in the medicaments or methods of the invention is a freeze dried extract.
  • the invention further comprises dosage forms comprising an extract of the invention.
  • the extract is provided in a substantially dry form, for example a freeze- dried form.
  • the extract is provided in an aqueous solution, for example water, saline or a buffer solution.
  • the dosage form is encapsulated, for example encapsulated with an enteric coating.
  • a pharmaceutical composition comprising an extract of the invention.
  • the medicaments or methods of the invention may be used for the prevention of nosocomial infections. In a particularly preferred embodiment they may be used for the prevention of nosocomial diarrhoea. In such an embodiment the medicaments or methods of the invention may be employed prophylactically to prevent a patient developing nosocomial diarrhoea. When used in accordance with this embodiment, the medicaments or methods of the invention will allow the maintenance or re-establishment in the patient's digestive tract of a flora that does not cause nosocomial diarrhoea.
  • the medicaments or methods of the invention may be used for the treatment of nosocomial infections.
  • these may be infections associated with nosocomial diarrhoea.
  • the medicaments will be administered to a patient whose digestive tract flora has been altered in a manner that causes nosocomial diarrhoea, but the delivery of the extract will cause a beneficial digestive tract flora that is not associated with nosocomial diarrhoea to be established. The establishment of this beneficial digestive tract flora will thus allow the digestive tract to function such that the nosocomial diarrhoea ends.
  • the medicaments or methods of the invention may be of use in the prevention and/or treatment of nosocomial diarrhoea arising as a result of any of a number of different causes. It may be preferred that the nosocomial diarrhoea to be prevented and/or treated is associated with antibiotic treatment, but the medicaments or methods of the invention are also applicable to the prevention or treatment of nosocomial diarrhoea caused by chemotherapy or radiotherapy.
  • the medicaments or methods of the invention are preferably of use in the prevention and/or treatment of nosocomial diarrhoea associated with C. Difficile infection.
  • C. Difficile is the species associated with the most common and most severe forms of nosocomial diarrhoea.
  • the medicaments or methods of the invention will preferably use a sample representative of the flora of a healthy digestive tract.
  • a "healthy" digestive tract is one that is not subject to nosocomial diarrhoea, without reference to other health considerations.
  • a healthy digestive tract may be one where C. difficile is present, but is kept in check by other constituents of the digestive tract flora. Although C difficile carriage is uncommon in healthy adults (1 %-3%) it is more common in debilitated patients and antibiotic-treated hospitalised adults (15%-25%), including those who receive antibiotics before surgery.
  • the patient's digestive tract may be considered “healthy” as long as the patient is not suffering from nosocomial diarrhoea or another nosocomial or iatrogenic disease of the digestive tract, even if the patient has other health concerns (such as those causing the patient to be admitted to hospital).
  • an extract representative of the flora of a patient's healthy digestive tract may be obtained from a sample collected prior to the initiation of any treatment (e.g. antibiotic treatment, radiotherapy or chemotherapy) that may cause nosocomial diarrhoea, or otherwise degrade the gastrointestinal flora and provide conditions in which C. difficile may flourish.
  • the medicaments or methods of the invention may be of particular use in the prevention and/or treatment of nosocomial infections that may otherwise be expected to occur in such individuals.
  • the medicaments or methods of the invention may be particularly suitable for use to prevent and/or treat nosocomial infections of individuals selected from the group consisting of: those undergoing (or about to undergo) antibiotic treatment; those undergoing (or about to undergo) radiotherapy (and in particular radiation of the pelvis); those undergoing (or about to undergo) chemotherapy; those undergoing (or about to undergo) immunosuppressive therapy; those undergoing (or about to undergo) treatment with proton pump inhibitors; those that have been subject to recurrent nosocomial infections; patients suffering from renal dysfunction; and the elderly.
  • Patients entering hospital and who require immediate treatment may provide a faecal smear which can be cultured in the laboratory to provide an enhanced sample for freeze drying that is capable of restoring their intestinal flora after their treatment ceases, in order to prevent the onset of nosocomial infection.
  • the medicaments or methods of the invention be used in the prevention and/or treatment of nosocomial infections of human patients they may also be suitable for use in non-human animals, for example domestic animals such as cats and dogs or farm animals such as cows, sheep and pigs.
  • domestic animals such as cats and dogs
  • farm animals such as cows, sheep and pigs.
  • sources of samples and extracts, and the calculation of therapeutically effective amounts, may be altered as required.
  • Extracts suitable for use in the medicaments or methods of the invention may be prepared from stool samples or from rectal swabs.
  • the stool may be fully or partially dissolved in a solvent such as sterile water or saline.
  • a solvent such as sterile water or saline.
  • the process of dissolution may be aided by homogenisation using techniques such as sonication or shaking.
  • the solvent and any homogenisation technique employed should be selected with a view to maintaining viability of the digestive tract flora within the sample (i.e. to prevent the death of bacteria through toxic effects or bacterial cell lysis). Filtration may then be used to remove solid materials from the solution, thus yielding an extract that is representative of the flora of the digestive tract.
  • flora present on the swab may be expanded by culture in suitable conditions. Suitable media and other culture conditions that may be used in the expansion of digestive tissue flora (typically utilising anaerobic culture conditions) will be well known to those skilled in the art. Different culture conditions may be used to allow the expansion of different components present in an extract for use in the medicaments or methods of the invention. If such an embodiment is to be used then the different cultures produced after such expansion may be combined to provide a therapeutically effective extract.
  • the extract is prepared, it may be preferred that it is dried prior to its encapsulation. This decreases the volume of the extract and increases its stability, allowing storage before use.
  • the dried extract may be stored either prior to encapsulation (e.g. in suitable vials, or the like) or after encapsulation or microencapsulation. It is preferred that dried extracts be produced by freeze drying.
  • an individual from whom an extract will be derived be provided with a standardised diet prior to sample collection. This may assist in removing variations in the consistency and floral content of samples.
  • a method of producing a medicament for the prevention and/or treatment of an iatrogenic disease of the digestive tract comprising: i) treating a faecal sample to produce an extract representative of the digestive flora of the individual from whom the faecal sample was obtained;
  • a method of producing a medicament for the prevention and/or treatment of a nosocomial infection of the digestive tract comprising:
  • the faecal sample may preferably comprise a stool sample or an anal swab.
  • the treatment step may optionally comprise one or more of the following: addition of a diluent (such as sterile water or sterile saline); sonication; shaking, filtration; and expansion of bacterial constituents within the sample.
  • a diluent such as sterile water or sterile saline
  • the drying step may preferably comprise freeze drying of the extract.
  • the invention further comprises a method of drying, for example freeze drying, an extract representative of the digestive flora of an individual.
  • the encapsulation step may preferably comprise packing of the dried extract into an enteric capsule, or formulation of the dried extract into a coated tablet, and should also be taken to encompass microencapsulation.
  • Such a system may comprise a software program which allows recording and tracking of samples and extracts and detection systems, such as the use of RFID tags, to track the samples and extracts.
  • a method of implementing such a system is another embodiment of the invention.
  • Figure 1 a shows a scheme for the collection and storage of stool sample for the preparation of extracts representative of the flora of the digestive tract
  • Figure 1 b shows a scheme for the preparation of extracts representative of the flora of the digestive tract from stored samples.
  • Figure 2 shows a scheme showing allogenic rehabilitation of iatorgenically degraded gastrointestinal flora..
  • This process is also compared to the health status of the patient, as the patient passes from a healthy state, through the development of an iatrogenic disease, and to healthy state in which the medicaments of the invention have rehabilitated the flora of the patient's digestive tract.
  • the patient provides a sample in a secure container with saline solution while their intestinal flora is still healthy.
  • sample and saline solution are homogenised in the sample container on a mechanical shaker.
  • the homogenised sample is attached to the filter unit.
  • the sample is now ready to be filtered.
  • a vacuum or pressure may be applied to the apparatus, for example a vacuum port of a filter unit, in order to carry out the filtration process.
  • the filtrate container is removed from the filter unit.
  • the sample container and filter unit are disposed of.
  • a lyophilisation membrane for example an expanded polytetrafluoroethylene membrane (ePTFE),. is placed on the filtrate container and the filtrate is freeze dried yielding a powdered product.
  • ePTFE expanded polytetrafluoroethylene membrane
  • the powdered product is dispensed into individual capsules using a capsule filling attachment.
  • the capsules are capped off and the filtrate container and capsule filling attachment are disposed of.
  • An RFID tag is attached to the capsule or the capsules are placed in a container with an RFID tag and other identifying data attached.
  • the capsules are enteric coated and ready to be used by the patient.
  • the RFID tag can be removed before consumption, or may be used to monitor degeneration of the capsule within the patient.
  • the patient can be treated with the capsules to rehabilitatise the flora of the patient's digestive tract.
  • Example 1 a An alternative approach to Example 1 a is to take a sample from a patient, tag the sample and store it and then only process the sample if the patient develops an iatrogenic disease. This procedure could be implemented as follows:
  • the patient who wears an RFID wristband, supplies a sample, for example a faecal sample, onto a plastic film in a bedpan [ Figure 1 a - (1 )].
  • the container is capped and placed at a known location in a refrigerator at about 4°C
  • the location of the samples are stored in an electronic location device on the refrigerator exterior.
  • the sample is stored until required. For example, it is used if the patient develops an iatrogenic disease, such as a C. difficile infection.
  • the sample is located using the location device and identified from the RFID tag using an RFID reader.
  • the sample is removed from the refrigerator and a fixed volume of saline or sterile water added [Figure 1 b - (6)].
  • the volume of water/saline will depend on the size of the sample.
  • the second container is sealed with a porous membrane, such as a LyoguardTM membrane (W. L. Gore & Associates, Inc, Newark, USA) and the sample freeze dried.
  • a porous membrane such as a LyoguardTM membrane (W. L. Gore & Associates, Inc, Newark, USA) and the sample freeze dried.
  • the powdered product is encapsulated using one of a range of encapsulation technologies, for example microencapsulation using an electrostatic generator [ Figure 2 -
  • the capsules are enteric coated.
  • a number of normal stool samples were examined to assess the quantitative effects of freeze drying on bacterial numbers. Normal stool samples were examined before and after the freeze drying process to compare bacterial numbers. A stool sample was received from each of five anonymous volunteers. Age and sex were supplied, and none of the volunteers had received antibiotics in the previous 3 months, or undergone any surgical procedures in the previous 12 months. All samples were examined for bacterial pathogens and processed for bacterial counts.
  • XLD xylose lactose deoxycholate citrate
  • Campylobacter medium comprises Columbia/brucella agar base, Horse blood (5%) Antibiotic supplement (cyclohexamide, cephazolin, novobiocin, bacitracin, colistin sulphate).
  • the plates were labeled and inoculated with the faecal sample using a cotton swab which had been dipped into the sample.
  • XLD, DCA and selenite were incubated overnight in air at 35-37°C. Plates were examined at 24 hours and the selenite broth subcultured to XLD which was incubated for 24 hours and examined as previously.
  • Campylobacter medium was incubated for 48hours in a jar with microaerophillic atmosphere.
  • C. difficile agar was incubated for 48hrs anaerobically.
  • MRS medium (De Man, Rogosa, Sharpe agar, a selective medium for lactic acid bacilli.)
  • Table 1 Bacterial count on faecal samples before freeze drying
  • Table 2 Bacterial count on freeze dried samples
  • anaerobic count decreased by 1 -2 logs following freeze drying but this was dependant upon the sample.
  • the aerobic count increased slightly (based on counts on (Blood agar and MacConkey medium). This would indicate that the aerobic bacteria survived freeze drying better than the anaerobic bacteria. Therefore, freeze drying does not markedly alter the pattern or numbers of bacterial flora present in a faecal sample.

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Abstract

La présente invention porte sur des médicaments pour la prévention et/ou le traitement d'infections nosocomiales, et sur des procédés de fabrication de ces médicaments. L'invention porte également sur des procédés de prévention et/ou de traitement de maladies iatrogéniques. Les médicaments et les procédés sont particulièrement appropriés pour le traitement d'infections nosocomiales provoquées par la diarrhée et pour la réhabilitation de l'iatrogène de la flore intestinale dégradée. L'invention porte en outre sur des médicaments comprenant un extrait représentatif de la flore du tube digestif.
PCT/GB2010/051561 2009-09-17 2010-09-17 Flore intestinale encapsulée extraite de fèces destinée à être utilisée dans le traitement de troubles gastro-intestinaux WO2011033310A1 (fr)

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Cited By (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012016287A2 (fr) * 2010-08-04 2012-02-09 Borody Thomas J Compositions pour une transplantation florale de matières fécales et leurs procédés de fabrication et d'utilisation et dispositifs pour leur administration
WO2013053836A1 (fr) 2011-10-11 2013-04-18 Quantum Pharmaceuticals Sa Composition comprenant un microbiote intestinal humain cultivé en conditions anaérobie
WO2013090825A1 (fr) * 2011-12-15 2013-06-20 Pureflora, Inc. Dispositif de collecte, de raffinage et d'administration de microflore gastro-intestinale
WO2013171515A1 (fr) * 2012-05-18 2013-11-21 Genome Research Limited Procédés et groupes
WO2014078911A1 (fr) * 2012-11-26 2014-05-30 Borody Thomas J Compositions pour la restauration d'un microbiote fécal et leurs procédés de fabrication et d'utilisation
WO2014152484A1 (fr) * 2013-03-14 2014-09-25 Regents Of The University Of Minnesota Microbiote fécal lyophilisé à utiliser dans la transplantation microbienne fécale
WO2014190229A1 (fr) * 2013-05-24 2014-11-27 President And Fellows Of Harvard College Procédés d'isolation de microorganismes et leurs utilisations
US8906668B2 (en) 2012-11-23 2014-12-09 Seres Health, Inc. Synergistic bacterial compositions and methods of production and use thereof
WO2014153194A3 (fr) * 2013-03-14 2014-12-11 Seres Health, Inc. Procédés de détection de pathogènes et d'enrichissement à partir de matériaux et de compositions
US9011834B1 (en) 2013-02-04 2015-04-21 Seres Health, Inc. Compositions and methods
US9320763B2 (en) 2000-07-25 2016-04-26 Thomas Julius Borody Probiotic recolonisation therapy
GB2533000A (en) * 2014-12-07 2016-06-08 Margaret Craig Nicola Humanized gastrointestinal microbiota
WO2016133450A1 (fr) 2015-02-19 2016-08-25 Achim Biotherapeutics Ab Composition thérapeutique et prophylactique produite par le microbiote
US9433651B2 (en) 2013-06-05 2016-09-06 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9463208B2 (en) 2010-02-01 2016-10-11 Rebiotix, Inc. Bacteriotherapy for clostridium difficile colitis
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US9649343B2 (en) 2011-03-09 2017-05-16 National Institutes of Health (NIH); U.S. Department of Health and Human Services (DHHS); The United States of America, NIH Division of Extramural Inventions and Tehnology Resources (DEITR) Compositions and methods for transplantation of colon microbiota
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US9956282B2 (en) 2013-12-16 2018-05-01 Seres Therapeutics, Inc. Bacterial compositions and methods of use thereof for treatment of immune system disorders
WO2018140931A1 (fr) * 2017-01-30 2018-08-02 The Board Of Regents Of The University Of Texas System Compositions et procédés de transplantation de microbiote fécal
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US10195235B2 (en) 2016-08-03 2019-02-05 Crestovo Holdings Llc Methods for treating ulcerative colitis
US10226431B2 (en) 2015-06-09 2019-03-12 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10258655B2 (en) 2013-11-25 2019-04-16 Seres Therapeutics, Inc. Synergistic bacterial compositions and methods of production and use thereof
US10383901B2 (en) 2013-06-05 2019-08-20 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
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US10905726B2 (en) 2015-06-09 2021-02-02 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
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US11433102B2 (en) 2017-04-05 2022-09-06 Finch Therapeutics Holdings Llc Compositions and methods for treating Parkinson's disease (PD) and related disorders
US11542560B2 (en) 2012-05-25 2023-01-03 Board of Regents on Behalf of Arizona State University Microbiome markers and therapies for autism spectrum disorders
US11680257B2 (en) 2015-05-11 2023-06-20 Mybiotics Pharma Ltd. Systems and methods for growing a biofilm of probiotic bacteria on solid particles for colonization of bacteria in the gut
US11679136B2 (en) 2016-05-25 2023-06-20 Mybiotics Pharma Ltd. Composition and methods for microbiota therapy
US11701394B2 (en) 2017-08-14 2023-07-18 Seres Therapeutics, Inc. Compositions and methods for treating cholestatic disease
US11819523B2 (en) 2016-07-01 2023-11-21 Regents Of The University Of Minnesota Compositions and methods for C. difficile treatment
US11865145B2 (en) 2017-08-07 2024-01-09 Finch Therapeutics Holdings Llc Compositions and methods for maintaining and restoring a healthy gut barrier
US11911419B2 (en) 2018-09-27 2024-02-27 Finch Therapeutics Holdings Llc Compositions and methods for treating epilepsy and related disorders

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990001335A1 (fr) * 1988-08-02 1990-02-22 Borody Thomas J Traitement de troubles gastro-intestinaux
WO1996038159A1 (fr) * 1995-06-02 1996-12-05 Lafor Laboratories Limited Lactobacilles micro-encapsules a applications medicales
WO1999049875A1 (fr) * 1998-03-27 1999-10-07 Cadila Pharmaceuticals (E.A.) Ltd. Procede de preparation d'une composition pharmaceutique de dose fixe stable, faite d'un ou de plusieurs agents anti-infectieux et de micro-organismes comme principes actifs
WO2002007741A1 (fr) * 2000-07-25 2002-01-31 Borody Thomas J Therapie par recolonisation avec des probiotiques
WO2006127355A2 (fr) * 2005-05-20 2006-11-30 Dow Global Technologies Inc. Controle de l'observance d'un medicament oral a l'aide d'etiquettes d'identification par radiofrequence
WO2008077614A2 (fr) * 2006-12-22 2008-07-03 Roland Saur-Brosch Utilisation d'une composition de substances minérales et éventuellement de bactéries acétogènes et/ou butyrogènes pour empêcher ou diminuer la formation de gaz dans le gros intestin d'un mammifère et les douleurs abdominales qui en résultent
WO2009068656A1 (fr) 2007-11-30 2009-06-04 Teagasc, The Agriculture And Food Development Authority Thuricine cd, un antimicrobien pour cibler spécifiquement clostridium difficile

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990001335A1 (fr) * 1988-08-02 1990-02-22 Borody Thomas J Traitement de troubles gastro-intestinaux
WO1996038159A1 (fr) * 1995-06-02 1996-12-05 Lafor Laboratories Limited Lactobacilles micro-encapsules a applications medicales
WO1999049875A1 (fr) * 1998-03-27 1999-10-07 Cadila Pharmaceuticals (E.A.) Ltd. Procede de preparation d'une composition pharmaceutique de dose fixe stable, faite d'un ou de plusieurs agents anti-infectieux et de micro-organismes comme principes actifs
WO2002007741A1 (fr) * 2000-07-25 2002-01-31 Borody Thomas J Therapie par recolonisation avec des probiotiques
WO2006127355A2 (fr) * 2005-05-20 2006-11-30 Dow Global Technologies Inc. Controle de l'observance d'un medicament oral a l'aide d'etiquettes d'identification par radiofrequence
WO2008077614A2 (fr) * 2006-12-22 2008-07-03 Roland Saur-Brosch Utilisation d'une composition de substances minérales et éventuellement de bactéries acétogènes et/ou butyrogènes pour empêcher ou diminuer la formation de gaz dans le gros intestin d'un mammifère et les douleurs abdominales qui en résultent
WO2009068656A1 (fr) 2007-11-30 2009-06-04 Teagasc, The Agriculture And Food Development Authority Thuricine cd, un antimicrobien pour cibler spécifiquement clostridium difficile

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REED; KEMMERLY, THE OCHSNER JOURNAL, vol. 9, 2009, pages 27 - 31

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US9463208B2 (en) 2010-02-01 2016-10-11 Rebiotix, Inc. Bacteriotherapy for clostridium difficile colitis
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US9176026B2 (en) 2011-12-15 2015-11-03 Pureflora, Inc. Device for the collection, refinement, and administration of gastrointestinal microflora
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WO2013171515A1 (fr) * 2012-05-18 2013-11-21 Genome Research Limited Procédés et groupes
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US11458173B2 (en) 2012-11-23 2022-10-04 Seres Therapeutics, Inc. Synergistic bacterial compositions and methods of production and use thereof
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WO2014078911A1 (fr) * 2012-11-26 2014-05-30 Borody Thomas J Compositions pour la restauration d'un microbiote fécal et leurs procédés de fabrication et d'utilisation
US9585921B2 (en) 2013-02-04 2017-03-07 Seres Therapeutics, Inc. Compositions and methods
US9011834B1 (en) 2013-02-04 2015-04-21 Seres Health, Inc. Compositions and methods
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US9446080B2 (en) 2013-02-04 2016-09-20 Seres Therapeutics, Inc. Compositions and methods
US9180147B2 (en) 2013-02-04 2015-11-10 Seres Therapeutics, Inc. Compositions and methods
US10064901B2 (en) 2013-02-04 2018-09-04 Seres Therapeutics, Inc. Compositions and methods
US10064900B2 (en) 2013-02-04 2018-09-04 Seres Therapeutics, Inc. Methods of populating a gastrointestinal tract
WO2014152484A1 (fr) * 2013-03-14 2014-09-25 Regents Of The University Of Minnesota Microbiote fécal lyophilisé à utiliser dans la transplantation microbienne fécale
WO2014153194A3 (fr) * 2013-03-14 2014-12-11 Seres Health, Inc. Procédés de détection de pathogènes et d'enrichissement à partir de matériaux et de compositions
US11666612B2 (en) 2013-03-15 2023-06-06 Seres Therapeutics, Inc Network-based microbial compositions and methods
US10076546B2 (en) 2013-03-15 2018-09-18 Seres Therapeutics, Inc. Network-based microbial compositions and methods
US10881696B2 (en) 2013-03-15 2021-01-05 Seres Therapeutics, Inc. Network-based microbial compositions and methods
WO2014190229A1 (fr) * 2013-05-24 2014-11-27 President And Fellows Of Harvard College Procédés d'isolation de microorganismes et leurs utilisations
US10471107B2 (en) 2013-06-05 2019-11-12 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9511099B2 (en) 2013-06-05 2016-12-06 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10688137B2 (en) 2013-06-05 2020-06-23 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10434125B2 (en) 2013-06-05 2019-10-08 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9694039B2 (en) 2013-06-05 2017-07-04 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US11554143B2 (en) 2013-06-05 2023-01-17 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10624932B2 (en) 2013-06-05 2020-04-21 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10610547B2 (en) 2013-06-05 2020-04-07 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10603341B2 (en) 2013-06-05 2020-03-31 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10391129B2 (en) 2013-06-05 2019-08-27 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9433651B2 (en) 2013-06-05 2016-09-06 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9782445B2 (en) 2013-06-05 2017-10-10 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10493111B2 (en) 2013-06-05 2019-12-03 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10434124B2 (en) 2013-06-05 2019-10-08 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9511100B2 (en) 2013-06-05 2016-12-06 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10434126B2 (en) 2013-06-05 2019-10-08 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9642880B2 (en) 2013-06-05 2017-05-09 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10383901B2 (en) 2013-06-05 2019-08-20 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US9675648B2 (en) 2013-06-05 2017-06-13 Rebiotix, Inc. Microbiota restoration therapy (MRT), compositions and methods of manufacture
US10258655B2 (en) 2013-11-25 2019-04-16 Seres Therapeutics, Inc. Synergistic bacterial compositions and methods of production and use thereof
US11918612B2 (en) 2013-11-25 2024-03-05 Seres Therapeutics, Inc. Synergistic bacterial compositions and methods of production and use thereof
US11266699B2 (en) 2013-11-25 2022-03-08 Seres Therapeutics, Inc. Synergistic bacterial compositions and methods of production and use thereof
US9956282B2 (en) 2013-12-16 2018-05-01 Seres Therapeutics, Inc. Bacterial compositions and methods of use thereof for treatment of immune system disorders
GB2533000A (en) * 2014-12-07 2016-06-08 Margaret Craig Nicola Humanized gastrointestinal microbiota
WO2016133450A1 (fr) 2015-02-19 2016-08-25 Achim Biotherapeutics Ab Composition thérapeutique et prophylactique produite par le microbiote
US11680257B2 (en) 2015-05-11 2023-06-20 Mybiotics Pharma Ltd. Systems and methods for growing a biofilm of probiotic bacteria on solid particles for colonization of bacteria in the gut
JP2020121996A (ja) * 2015-05-14 2020-08-13 クレストヴォ・ホールディングス・エルエルシー 便フローラを移植するための組成物、並びにそれを調製及び使用する方法、並びにそれを送達するためのデバイス
US11123377B2 (en) 2015-05-14 2021-09-21 Finch Therapeutics Holdings Llc Compositions for fecal floral transplantation and methods for making and using them and device for delivering them
US9901603B2 (en) 2015-05-14 2018-02-27 Crestovo Holdings Llc Compositions for fecal floral transplantation and methods for making and using them and device for delivering them
JP2018515617A (ja) * 2015-05-14 2018-06-14 クレストヴォ・ホールディングス・エルエルシー 便フローラを移植するための組成物、並びにそれを調製及び使用する方法、並びにそれを送達するためのデバイス
JP7301107B2 (ja) 2015-05-14 2023-06-30 フィンチ セラピューティクス ホールディングス エルエルシー 便フローラを移植するための組成物、並びにそれを調製及び使用する方法、並びにそれを送達するためのデバイス
JP2022009354A (ja) * 2015-05-14 2022-01-14 フィンチ セラピューティクス ホールディングス エルエルシー 便フローラを移植するための組成物、並びにそれを調製及び使用する方法、並びにそれを送達するためのデバイス
US10821138B2 (en) 2015-05-14 2020-11-03 Crestovo Holdings Llc Compositions for fecal floral transplantation and methods for making and using them and device for delivering them
US11202808B2 (en) 2015-05-22 2021-12-21 Arizona Board Of Regents On Behalf Of Arizona State University Methods for treating autism spectrum disorder and associated symptoms
US11642381B2 (en) 2015-06-09 2023-05-09 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10828340B2 (en) 2015-06-09 2020-11-10 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10226431B2 (en) 2015-06-09 2019-03-12 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10799539B2 (en) 2015-06-09 2020-10-13 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US11654164B2 (en) 2015-06-09 2023-05-23 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10905726B2 (en) 2015-06-09 2021-02-02 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US10391064B2 (en) 2015-06-09 2019-08-27 Rebiotix, Inc. Microbiota restoration therapy (MRT) compositions and methods of manufacture
US11679136B2 (en) 2016-05-25 2023-06-20 Mybiotics Pharma Ltd. Composition and methods for microbiota therapy
US11357801B2 (en) 2016-06-15 2022-06-14 Arizona Board Of Regents On Behalf Of Arizona State University Methods for treating autism spectrum disorder and associated symptoms
US11819523B2 (en) 2016-07-01 2023-11-21 Regents Of The University Of Minnesota Compositions and methods for C. difficile treatment
US11071759B2 (en) 2016-08-03 2021-07-27 Finch Therapeutics Holdings Llc Methods for treating ulcerative colitis
US10195235B2 (en) 2016-08-03 2019-02-05 Crestovo Holdings Llc Methods for treating ulcerative colitis
US10561690B2 (en) 2016-08-03 2020-02-18 Crestovo Holdings Llc Methods for treating ulcerative colitis
US10092601B2 (en) 2016-10-11 2018-10-09 Crestovo Holdings Llc Compositions and methods for treating multiple sclerosis and related disorders
US11213549B2 (en) 2016-10-11 2022-01-04 Finch Therapeutics Holdings Llc Compositions and method for treating primary sclerosing cholangitis and related disorders
US11026978B2 (en) 2016-10-11 2021-06-08 Finch Therapeutics Holdings Llc Compositions and methods for treating multiple sclerosis and related disorders
WO2018140931A1 (fr) * 2017-01-30 2018-08-02 The Board Of Regents Of The University Of Texas System Compositions et procédés de transplantation de microbiote fécal
US11040073B2 (en) 2017-04-05 2021-06-22 Finch Therapeutics Holdings Llc Compositions and methods for treating diverticulitis and related disorders
US11529375B2 (en) 2017-04-05 2022-12-20 Finch Therapeutics Holdings Llc Compositions and methods for treating diverticulitis and related disorders
US11433102B2 (en) 2017-04-05 2022-09-06 Finch Therapeutics Holdings Llc Compositions and methods for treating Parkinson's disease (PD) and related disorders
US11890306B2 (en) 2017-05-26 2024-02-06 Finch Therapeutics Holdings Llc Lyophilized compositions comprising fecal microbe-based therapeutic agents and methods for making and using same
WO2018218159A1 (fr) 2017-05-26 2018-11-29 Crestovo Holdings Llc Compositions lyophilisées comprenant des agents thérapeutiques à base de microbes fécaux et leurs procédés de fabrication et d'utilisation
US11865145B2 (en) 2017-08-07 2024-01-09 Finch Therapeutics Holdings Llc Compositions and methods for maintaining and restoring a healthy gut barrier
US11701394B2 (en) 2017-08-14 2023-07-18 Seres Therapeutics, Inc. Compositions and methods for treating cholestatic disease
US11166990B2 (en) 2018-07-13 2021-11-09 Finch Therapeutics Holdings Llc Methods and compositions for treating ulcerative colitis
CN112888447A (zh) * 2018-08-17 2021-06-01 韦丹塔生物科学股份有限公司 减少菌群失调和恢复微生物群系的方法
US20220143108A1 (en) * 2018-08-17 2022-05-12 Vedanta Biosciences, Inc. Methods of decreasing dysbiosis and restoring a microbiome
US11911419B2 (en) 2018-09-27 2024-02-27 Finch Therapeutics Holdings Llc Compositions and methods for treating epilepsy and related disorders
WO2021050965A1 (fr) 2019-09-13 2021-03-18 Crestovo Holdings Llc Compositions et méthodes de traitement de trouble du spectre autistique
WO2021077107A1 (fr) 2019-10-18 2021-04-22 Crestovo Holdings Llc Compositions et procédés pour administrer un métabolite bactérien à un sujet
WO2021097288A1 (fr) 2019-11-15 2021-05-20 Finch Therapeutics Holdings Llc Compositions et méthodes de traitement de maladies neurodégénératives
WO2021142353A1 (fr) 2020-01-10 2021-07-15 Finch Therapeutics Holdings Llc Compositions et méthodes pour le traitement de l'hépatite b (vhb) et de l'hépatite d (vhd)
WO2021142358A1 (fr) 2020-01-10 2021-07-15 Finch Therapeutics Holdings Llc Compositions et méthodes pour le traitement de l'encéphalopathie hépatique (eh)
WO2021142347A1 (fr) 2020-01-10 2021-07-15 Finch Therapeutics Holdings Llc Compositions et procédés relatifs à la stéatohépatite non alcoolique (nash)
WO2021202806A1 (fr) 2020-03-31 2021-10-07 Finch Therapeutics Holdings Llc Compositions comprenant un microbiome fécal non viable et leurs méthodes d'utilisation
CN114686556A (zh) * 2020-12-31 2022-07-01 石家庄市疾病预防控制中心（石家庄市卫生检测中心） 一种胃内菌群的检测方法

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