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WO2006117573A1 - Polytherapie - Google Patents

Polytherapie Download PDF

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Publication number
WO2006117573A1
WO2006117573A1 PCT/GB2006/050090 GB2006050090W WO2006117573A1 WO 2006117573 A1 WO2006117573 A1 WO 2006117573A1 GB 2006050090 W GB2006050090 W GB 2006050090W WO 2006117573 A1 WO2006117573 A1 WO 2006117573A1
Authority
WO
WIPO (PCT)
Prior art keywords
receptor antagonist
opioid receptor
composition
mammal
peptide
Prior art date
Application number
PCT/GB2006/050090
Other languages
English (en)
Inventor
Deirdre Mcintosh
Original Assignee
Aimsco Limited
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 Aimsco Limited filed Critical Aimsco Limited
Publication of WO2006117573A1 publication Critical patent/WO2006117573A1/fr

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Classifications

    • 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
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/095—Oxytocins; Vasopressins; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/2228—Corticotropin releasing factor [CRF] (Urotensin)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Definitions

  • the present invention relates to a combination therapy for treatment of, inter alia, multiple sclerosis.
  • the therapy may also be used to treat other disorders.
  • Naltrexone (17-(cyclopropylmethyl)-4,5 ⁇ -epoxy-3,14- dihydroxymorphinan-6-one) is an opioid receptor antagonist, and was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs.
  • naltrexone By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that the brain and adrenal glands produce: beta-endorphin and met-enkephalin. Many organs in the body have receptors for these endorphins and enkephalins, including virtually every cell of the body's immune system.
  • LDN Low dose naltrexone
  • cancers including cancers, multiple sclerosis, autoimmune diseases, and HIV.
  • LDN has been indicated as a treatment for the following cancers: Breast Cancer; Carcinoid; Colon & Rectal Cancer; Glioblastoma; Liver Cancer; Lung Cancer (Non-Small Cell); Lymphocytic Leukemia; Lymphoma (Hodgkin's and Non-Hodgkin's); Malignant Melanoma; Multiple Myeloma; Neuroblastoma; Ovarian Cancer; Pancreatic Cancer; Prostate Cancer (untreated); Renal Cell Carcinoma; Throat Cancer; Uterine Cancer.
  • LDN may also be used for treatment of other diseases including ALS (Lou Gehrig's Disease); Alzheimer's Disease; Behcet's Disease; Celiac Disease; Chronic Fatigue Syndrome; Crohn's Disease; Emphysema (COPD); Fibromyalgia; HIV/AIDS; Irritable Bowel Syndrome (IBS); Multiple Sclerosis (MS); Parkinson's Disease; Pemphigoid; Primary Lateral Sclerosis (PLS); Psoriasis; Rheumatoid Arthritis; Sarcoidosis; Systemic Lupus (SLE); Ulcerative Colitis; Wegener's Granulomatosis
  • ALS Longou Gehrig's Disease
  • Alzheimer's Disease Alzheimer's Disease
  • Behcet's Disease Celiac Disease
  • Chronic Fatigue Syndrome Crohn's Disease
  • Emphysema COPD
  • HIV/AIDS HIV/AIDS
  • IBS Irritable Bowel Syndrome
  • MS Multiple Sclerosis
  • PLS Primary Lateral
  • the therapeutic dosage range for LDN is from 1.75mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with their effectiveness.
  • MS multiple sclerosis
  • the usual adult dosage is 4.5mg taken orally (in tablet form) once daily, usually at night. People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
  • a goat is immunised with HIV-3B viral lysate raised in H9 cells.
  • the resulting serum is believed to be active against, among other disorders, multiple sclerosis.
  • the reader is further referred in particular to the section on pages 3 and 4 of WO03/004049 headed ⁇ xample of Production of Goat Serum' for further details of the production of serum. This section is incorporated herein by reference.
  • activity of the serum may be enhanced by administration of a suitable adjuvant to the mammal.
  • suitable adjuvants may include Freund's complete or incomplete adjuvant; Montanide's ISA adjuvant; Ribi's adjuvants; aluminium salt adjuvants; and nitrocellulose adsorbed protein.
  • suitable adjuvants which may be used. It is believed that administration of an adjuvant enhances production of immune system components which provide at least some of the activity of the serum.
  • Ungulates include artiodactyls, such as cattle, sheep, goats, pigs, camels and antelopes; and perissodactyls, for example horses.
  • a CRF peptide any peptide having a corresponding sequence, structure, or function to CRF.
  • CRF corticotropin releasing factor
  • POMC proopiomelanocortin
  • a CRF peptide any peptide having a corresponding sequence, structure, or function to CRF.
  • canonical nucleotide and/or amino acid sequences given for human CRF in GENBANK entry BCOl 1031 may be varied to a certain degree without affecting the structure or function of the peptide.
  • allelic variants and functional mutants are included within this definition. Mutants may include conservative amino acid substitutions; and fragments and derivatives of CRF.
  • POMC is a peptide (prohormone) produced in the pituitary gland (as well as a number of other organs, certain tumours such as melanomas, and normal skin cells) which is the precursor of a set of corticotrophic hormones which exert a number of effects on the host.
  • POMC is the precursor to alpha, beta, and gamma melanocyte stimulating hormone (MSH); adrenocorticotrophin (ACTH); beta and gamma lipotropin (LPH); and beta endorphin. All of these hormones are cleaved from a single large precursor, POMC, and are termed herein "POMC products".
  • a pharmaceutical composition comprising an opioid receptor antagonist and a serum composition obtained from an ungulate, preferably a goat, after challenge with an immunogen.
  • a pharmaceutical composition comprising an opioid receptor antagonist and a POMC peptide; the invention also provides a pharmaceutical composition comprising an opioid receptor antagonist and a CRF peptide.
  • aspects of the invention also provide a pharmaceutical composition comprising an opioid receptor antagonist and a serum composition obtained from a na ⁇ ve ungulate, preferably a goat.
  • a na ⁇ ve ungulate or goat is one which has not been pre-immunised with a specific immunogen.
  • the na ⁇ ve goat may be a conventional farm goat, and preferably a farm goat which has not been immunized. It is preferred that the goat has not previously encountered any immunogens.
  • the opioid receptor antagonist is naltrexone, or a pharmaceutically acceptable salt thereof.
  • composition may also comprise one or more peptide regulatory or releasing factors, which may induce a cascade of release of further peptides by a variety of cells in the patient.
  • Suitable factors include ⁇ -HLA, TGF- ⁇ , and IL-IO, among others.
  • the composition may comprise one or more of vasopressin, beta endorphin, and leu or met enkephalin.
  • the composition may comprise CRF binding protein, CRF-BP. This binds CRF and may act as a reservoir for subsequent release of CRF to the patient.
  • compositions of the invention may be accomplished orally or parenterally.
  • Methods of parenteral delivery include topical, intra-arterial, intramuscular, subcutaneous, intramedullary, intrathecal, intraventricular, intravenous, intraperitoneal, or intranasal administration.
  • compositions may comprise suitable pharmaceutically acceptable carriers comprising excipients and other components which facilitate processing of the active compounds into preparations suitable for pharmaceutical administration.
  • compositions for oral administration can be formulated using pharmaceutically acceptable carriers known in the art in dosages suitable for oral administration.
  • Such carriers enable the compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like suitable for ingestion by the subject.
  • compositions for oral use can be obtained through combination of active compounds with a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable additional compounds if desired to obtain tablets or dragee cores.
  • Suitable excipients include carbohydrate or protein fillers such as sugars, including lactose, sucrose, mannitol, sorbitol; starch from corn, wheat, rice, potato, or other plants; cellulose such as methylceiluiose, hydroxypropylmethylcellulose, or sodium carboxymethylceHulose; and gums including arabic and tragacanth; as well as proteins such as gelatin and collagen.
  • disintegrating or solubilising agents may be added, such as cross linked polyvinyl pyrrolidone, agar, alginic acid, or a salt thereof.
  • Dragee cores can be provided with suitable coatings such as concentrated sugar solutions, which may also contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for product identification or to characterise the quantity of active compound.
  • suitable coatings such as concentrated sugar solutions, which may also contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures.
  • Dyestuffs or pigments may be added to the tablets or dragee coatings for product identification or to characterise the quantity of active compound.
  • compositions which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a coating such as glycerol or sorbitol.
  • Push-fit capsules can contain active ingredients mixed with a filler or binders such as lactose or starches, lubricants such as talc or magnesium stearate, and, optionally stabilisers.
  • the active compounds can be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycol with or without stabilisers.
  • Pharmaceutical formulations for parenteral administration include aqueous solutions of active compounds.
  • the pharmaceutical compositions of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiologically buffered saline.
  • Aqueous suspension injections can contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran.
  • suspensions of the active compounds can be prepared as appropriate oily injection suspensions.
  • Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes.
  • the suspension can also contain suitable stabilisers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.
  • penetrants appropriate to the particular barrier to be permeated may be used in the formulation.
  • compositions of the present invention can be manufactured substantially in accordance with standard manufacturing procedures known in the art.
  • the invention also provides an opioid receptor antagonist and a serum composition obtained from an ungulate, preferably a goat after challenge with an immunogen, for use as a medicament. Also provided is an opioid receptor antagonist and a POMC peptide, for use as a medicament; the invention also provides an opioid receptor antagonist and a CRF peptide, for use as a medicament. Aspects of the invention also provide an opioid receptor antagonist and a serum composition obtained from a na ⁇ ve ungulate, preferably a goat, for use as a medicament.
  • a method of treatment of a disorder may comprise administering an opioid receptor antagonist and a serum composition obtained from an ungulate, preferably a goat after challenge with an immunogen; or an opioid receptor antagonist and a POMC peptide; or an opioid receptor antagonist and a CRF peptide; or an opioid receptor antagonist and a serum composition obtained from a naive ungulate, preferably a goat.
  • the two components may be administered sequentially or simultaneously; and may be administered as separate medicaments, or as a combined medicament.
  • the disorder may be selected from an autoimmune disorder, cancers, and HIV.
  • the disorder may be selected from multiple sclerosis; rheumatoid arthritis; optic neuritis; motor neurone disease; autoimmune diseases including lupus, psoriasis, eczema, thyroiditis, and polymyositis; axonal or nerve damage; cancers, in particular myelomas, melanomas, and lymphomas; neural disorders, both demyelinating and non-demyelinating; inflammatory conditions; obesity; nerve conduction disorders; and sexual dysfunction, in particular erectile dysfunction.
  • Other disorders which may be treated include Krabbes disease, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy.
  • the disorder may be selected from any of the conditions recited above for which LDN is noted as being useful.
  • the precise dosage to be administered may be varied depending on such factors as the age, sex and weight of the patient, the method and formulation of administration, as well as the nature and severity of the disorder to be treated. Other factors such as diet, time of administration, condition of the patient, drug combinations, and reaction sensitivity may be taken into account.
  • An effective treatment regimen may be determined by the clinician responsible for the treatment.
  • One or more administrations may be given, and typically the benefits are observed after a series of at least three, five, or more administrations.
  • the dosage may include 1.75 - 4 mg of naltrexone or other opioid antagonist, and i - 50 mg, or 1 - 25 mg, or 1 - 15 mg or 1 - 10 mg or 1 - 5 mg of serum composition, or POMC peptide, or CRF peptide.
  • the treatment may be administered by any effective route, preferably by subcutaneous injection, although alternative routes which may be used include intramuscular or intralesional injection, oral, aerosol, parenteral, or topical.
  • the treatment is preferably administered as a liquid formulation, although other formulations may be used.
  • the treatment may be mixed with suitable pharmaceutically acceptable carriers, and may be formulated as solids (tablets, pills, capsules, granules, etc) in a suitable composition for oral, topical or parenteral administration.
  • Approximately 400 ml of blood is taken from a goat under sterile technique, The animal may typically be re-bled in 10 to 14 days, once the volume of blood is replenished.
  • the blood is then centrifuged to separate the serum, and the serum filtered to remove large clots and particulate matter.
  • the serum is then treated with supersaturated ammonium sulphate (47% solution at room temperature) to precipitate antibodies and other material.
  • the resulting solution is centrifuged at 35000 rpm for 45 minutes at 4°C, after which the supernatant is removed.
  • the precipitated immunoglobulin and other solid material are resuspended in 47% ammonium sulphate/PBS and re-centrifuged as before.
  • PBS buffer phosphate buffered saline
  • the solution is then dialysed at 4°C through a membrane with a molecular weight cut-off of 10,000 Daltons. Dialysis is carried out in PBS buffer, changed every 4 hours over a period of 24 hours, at 4°C. After 12 hours of dialysis, the contents of the dialysis bag are emptied into a sterile container. The solution is adjusted to 5 mg/ml using PBS, and the resulting solution filtered through a 0.2 micron filter into a sterile container. After filtration the solution is divided into aliquots to give single doses of ImI, and stored at -15 - 25 0 C prior to use.
  • PBS buffer phosphate buffered saline
  • This solution comprises POMC peptides and CRF peptides. To this may be added a suitable dose of naltrexone, which may then be administered to a patient as appropriate.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Oncology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Emergency Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Biotechnology (AREA)
  • Developmental Biology & Embryology (AREA)

Abstract

La présente invention concerne une composition pharmaceutique comprenant l'antagoniste du récepteur opioïde naltrexone, et a) une composition sérique obtenue à partir d'un mammifère, de préférence une chèvre, après un test de provocation avec un immunogène; ou b) une composition sérique obtenue à partir d'un mammifère naïf, de préférence une chèvre; ou c) un peptide POMC; ou d) un peptide CRF. La composition est utile pour traiter, entre autres, des maladies telles que le VIH, certains cancers et la sclérose en plaques. Cette invention concerne également des méthodes permettant de traiter les maladies susmentionnées.
PCT/GB2006/050090 2005-05-04 2006-05-03 Polytherapie WO2006117573A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0509052.7A GB0509052D0 (en) 2005-05-04 2005-05-04 Combination therapy
GB0509052.7 2005-05-04

Publications (1)

Publication Number Publication Date
WO2006117573A1 true WO2006117573A1 (fr) 2006-11-09

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GB (1) GB0509052D0 (fr)
WO (1) WO2006117573A1 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007077465A3 (fr) * 2006-01-06 2007-11-08 Aimsco Ltd Traitement du vih
WO2009068668A1 (fr) * 2007-11-30 2009-06-04 Pharnext Nouvelles approches thérapeutiques dans le traitement de la cmt et des troubles associés
WO2010139627A1 (fr) * 2009-06-02 2010-12-09 Pharnext Nouvelles compositions pour le traitement du cmt et de troubles associés
WO2015170122A1 (fr) * 2014-05-08 2015-11-12 Aimsco Limited Formulation et méthode de production de celle-ci
US9393241B2 (en) 2009-06-02 2016-07-19 Pharnext Compositions for treating CMT and related disorders
AU2014202258B2 (en) * 2007-11-30 2016-08-11 Pharnext New therapeutic approaches for treating CMT and related disorders
JP2016524602A (ja) * 2013-05-10 2016-08-18 キャンサー ワクチン インスティテュート ナルトレキソンを用いたがんの処置
US9597297B2 (en) 2008-06-18 2017-03-21 Pharnext Combination of pilocarpin and methimazol for treating Charcot-Marietooth disease and related disorders
US10300015B2 (en) 2013-06-05 2019-05-28 Pharnext Stable oral solutions for combined API
US10383870B2 (en) 2016-06-10 2019-08-20 Pharnext Early treatment of CMT disease

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0373744A2 (fr) * 1988-12-15 1990-06-20 Baker Norton Pharmaceuticals, Inc. Utilisation du nalméfène ou du naltrexone dans le traitement des maladies auto-immunes
WO2003004049A2 (fr) * 2001-07-02 2003-01-16 Aimsco Limited Agent therapeutique
WO2003064472A2 (fr) * 2002-01-28 2003-08-07 Aimsco Limited Traitement
WO2005097183A2 (fr) * 2004-04-05 2005-10-20 Aimsco Limited Traitement de maladies
WO2006021814A2 (fr) * 2004-07-08 2006-03-02 Aimsco Limited Medicament

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0373744A2 (fr) * 1988-12-15 1990-06-20 Baker Norton Pharmaceuticals, Inc. Utilisation du nalméfène ou du naltrexone dans le traitement des maladies auto-immunes
WO2003004049A2 (fr) * 2001-07-02 2003-01-16 Aimsco Limited Agent therapeutique
WO2003064472A2 (fr) * 2002-01-28 2003-08-07 Aimsco Limited Traitement
WO2005097183A2 (fr) * 2004-04-05 2005-10-20 Aimsco Limited Traitement de maladies
WO2006021814A2 (fr) * 2004-07-08 2006-03-02 Aimsco Limited Medicament

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA015924B1 (ru) * 2006-01-06 2011-12-30 Эймско Лимитед Лечение вич
WO2007077465A3 (fr) * 2006-01-06 2007-11-08 Aimsco Ltd Traitement du vih
AU2007203991B2 (en) * 2006-01-06 2013-01-17 Aimsco Limited Treatment of HIV
US10322101B2 (en) 2007-11-30 2019-06-18 Pharnext Therapeutic approaches for treating CMT and related disorders
AU2014202258B2 (en) * 2007-11-30 2016-08-11 Pharnext New therapeutic approaches for treating CMT and related disorders
EA035711B1 (ru) * 2007-11-30 2020-07-29 Фарнекст Применение d-сорбита для лечения смт и связанных с ним расстройств
US10463640B2 (en) 2007-11-30 2019-11-05 Pharnext Therapeutic approaches for treating CMT and related disorders
EP2609916A1 (fr) * 2007-11-30 2013-07-03 Pharnext Nouvelles approches thérapeutiques pour traiter le CMT et troubles associés
EA019402B1 (ru) * 2007-11-30 2014-03-31 Фарнекст Композиции и способ лечения болезни шарко-мари-тусса
CN104257657A (zh) * 2007-11-30 2015-01-07 法奈科斯公司 用于治疗cmt和相关疾病的新治疗方法
US10441558B2 (en) 2007-11-30 2019-10-15 Pharnext Therapeutic approaches for treating CMT and related disorders
WO2009068668A1 (fr) * 2007-11-30 2009-06-04 Pharnext Nouvelles approches thérapeutiques dans le traitement de la cmt et des troubles associés
US8992891B2 (en) 2007-11-30 2015-03-31 Pharnext Therapeutic approaches for treating CMT and related disorders
CN104257657B (zh) * 2007-11-30 2017-07-04 法奈科斯公司 用于治疗cmt和相关疾病的治疗方法
US9597297B2 (en) 2008-06-18 2017-03-21 Pharnext Combination of pilocarpin and methimazol for treating Charcot-Marietooth disease and related disorders
EP2263665A1 (fr) * 2009-06-02 2010-12-22 Pharnext Nouvelles compositions pour traiter le CMT et troubles associés
JP2012528818A (ja) * 2009-06-02 2012-11-15 ファーネクスト Ｃｍｔ及び関連障害を処置するための新たな組成物
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CN102458387A (zh) * 2009-06-02 2012-05-16 法奈科斯公司 用于治疗cmt及相关病症的新组合物
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JP2016524602A (ja) * 2013-05-10 2016-08-18 キャンサー ワクチン インスティテュート ナルトレキソンを用いたがんの処置
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WO2015170122A1 (fr) * 2014-05-08 2015-11-12 Aimsco Limited Formulation et méthode de production de celle-ci
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