EP2519227A2 - Gestion de la myoclonie par le glutathion réduit liposomal oral - Google Patents

Gestion de la myoclonie par le glutathion réduit liposomal oral

Info

Publication number
EP2519227A2
EP2519227A2 EP10841709A EP10841709A EP2519227A2 EP 2519227 A2 EP2519227 A2 EP 2519227A2 EP 10841709 A EP10841709 A EP 10841709A EP 10841709 A EP10841709 A EP 10841709A EP 2519227 A2 EP2519227 A2 EP 2519227A2
Authority
EP
European Patent Office
Prior art keywords
administration
reduced glutathione
myoclonus
glutathione
treatment
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP10841709A
Other languages
German (de)
English (en)
Other versions
EP2519227A4 (fr
Inventor
F. Timothy Guilford
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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
Priority claimed from US12/649,698 external-priority patent/US20100166846A1/en
Application filed by Individual filed Critical Individual
Publication of EP2519227A2 publication Critical patent/EP2519227A2/fr
Publication of EP2519227A4 publication Critical patent/EP2519227A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K38/06—Tripeptides
    • A61K38/063—Glutathione
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • 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
    • A61K9/4858—Organic compounds
    • 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
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Definitions

  • This invention relates to a method of treatment of myoclonus and other illnesses related to mold toxin exposure after testing with a liposomal preparation of reduced glutathione and with a combination of a liposomal preparation of reduced glutathione and an anti- fungal agent.
  • the invention relates to a composition and method for the management of myoclonus and myoclonus and other illnesses related to mold toxin exposure.
  • the invention proposes the use of reduced glutathione encapsulated in a liposome (liposomal reduced glutathione) for the oral administration of a therapeutically effective amount to facilitate treatment of myoclonus.
  • the oral liposomal reduced glutathione is also proposed for the removal of mold toxin and to improve symptoms in disease states related to exposure to mold toxins.
  • the invention proposes a method of treatment combining an orally administrable preparation of liposomal glutathione with an anti- fungal agent.
  • the invention relates to the management of myoclonus and myoclonus related to mold toxin exposure with the delivery of reduced glutathione accomplished with the use of an oral liposomal preparation of reduced glutathione, uniquely designed to be absorbed a) across the mucosa of the nose, mouth, gastrointestinal tract, b) after topical application for transdermal, or c) by intravenous infusion of with or without liposome encapsulation.
  • BACKGROUND OF INVENTION The role of mold toxin in health has been difficult to assess as the relationship between mycotoxin and illness is often not appreciated unless the mold or yeast vector has been cultured from the blood of an infected individual.
  • Toxins from molds or yeast are generally referred to as mycotoxins. Illness related to the accumulation of toxins from mold or yeast is generally reported after the finding of toxin contamination in food for humans and more commonly in animal feed (1).
  • Indoor exposure to toxigenic mold has been proposed, but the ability to establish the presence of mold using reproducible clinical laboratory techniques has been lacking, so the concept remains largely conjectural and very controversial. Exposure to toxigenic mold has been conjectured to cause asthma, airway irritation and bleeding, dizziness, and impaired memory and concentration problems (2).
  • the inventor has conceived that surprising benefit of oral liposomal glutathione might be useful to be administered to an animal incapacitated by myoclonus and to the moderately affected human companion of the animal. Upon administration, the inventor has discovered significant lessening of the individual's symptoms as reviewed in Case Examples 1 and 2.
  • Myoclonus is a hyperkinetic movement disorder characterized by quick, involuntary jerks or movements. These movements can be localized to certain muscle groups or may be generalized to an area such as extremity. Myoclonus encompasses a vast range of etiologies and widespread anatomic locations. Treatment of myoclonus has been complicated by the fact that there is no known specific etiology. The majority of the literature is comprised of case reports (3). The inventor theorizes the myoclonus symptoms were related to mold toxins. Glutathione is known for its role in biochemical detoxification (4).
  • glutathione has not been commercially available in a form usable for ordinary patient treatment outside of a clinical setting despite having been reported from cell culture studies as far back as 1979 to neutralize the aflatoxin Bl (5).
  • glutathione has not been commercially available in a form usable for ordinary patient treatment outside of a clinical setting despite having been reported from cell culture studies as far back as 1979 to neutralize the aflatoxin Bl (5).
  • Myoclonus currently has no specific medication for treatment and, given the uncertain pathology and etiology, a treatment modality or paradigm, has not been developed.
  • a primary object of the invention is a composition and method of treating myoclonus by a liposomal reduced glutathione capable of effective oral administration while achieving the desired intracellular results specifically meaning capable of being absorbed a) across the mucosa of the nose, mouth, gastrointestinal tract, b) after topical application for transdermal, or c) by intravenous infusion of with or without liposome encapsulation.
  • a corollary and critical characteristic to liposomal reduced glutathione being
  • Liposomal reduced glutathione may also be considered in combination with antifungal medications for the management of fungal related illnesses and exposures, particularly if mycotoxins are found to be present in one or more body fluids or tissues of an individual.
  • Glutathione Or Precursor Such As NAC As An Adjunct In The Treatment Of Bacillus Anthracis Exposure Or Infection, of provisional application 60/371,590 filed on April 11, 2002 entitled Use Of Glutathione Precursor In The Treatment Of Smallpox And The Use Of Glutathione Precursor In The Treatment Of Radiation Exposure, The Use Of The Combination Of Glutathione Precursor And DHEA For The Treatment Of Smallpox And Other Viruses, all of which are incorporated by reference herein, and Liposomal
  • Statins have also been shown to have antifungal qualities, possibly due to the ability of statins to inhibit production of isoprenylated proteins that are essential to fungi (6).
  • Statins include: Simvastatin, fluvastatin, lovastatin, atorvastatin, rosuvastatin, pravastatin. Imidazoles are taken orally:
  • mice Miconazole - (Miconazole nitrate), Ketoconazole, Clotrimazole - marketed as Lotrimin or Lotrimin AF (and Canesten in the UK).
  • Sulconazole, Tioconazole Triazoles are taken orally:
  • Allylamines inhibit the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis:
  • Echinocandins inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3- ⁇ glucan synthase:
  • Ciclopirox - (ciclopirox olamine), Tolnaftate - fungicidal, marketed as Tinactin, Desenex, Aftate, as well as other names.
  • Flucytosine or 5-fluorocytosine, is an antimetabolite.
  • Griseofulvin - binds to polymerized microtubules and inhibits fungal mitosis.
  • the preferred combination is 200 mg of itraconazole orally per day for 2 to 16 weeks in combination with oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • the preferred combination is 200 mg of voriconazole orally per day for 2 to 16 weeks in combination with oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • Intranasal antifungal therapy in the form of irrigation or topical intranasal spray may also be used in combination with oral liposomal reduced glutathione. The objective of this therapy is to reduce the presence and growth of fungal material in the nose and adjacent sinuses.
  • oral liposomal reduced glutathione is oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • the preferred therapeutic for intranasal therapy is the preferred therapeutic for intranasal therapy.
  • Another preferred method for the nasal spray is to use 100 mg of fluconazole in 500 ml of normal saline solution administered as 5 sprays (0.5 cc/spray) in each nostril twice daily.
  • nasal spray is to use Itraconazole 0.1% Nasal Spray 5 sprays each nostril twice a day.
  • Plain glutathione used orally is not an option for this therapy as plain glutathione is not absorbed after oral ingestion in humans (7).
  • the tissue from the control animals (water) served as the 100% of the toxin remaining in the tissue.
  • Oral liposomal reduced glutathione that is uniquely designed to be absorbed a) across the mucosa of the nose, mouth, gastrointestinal tract, b) after topical application for transdermal, or c) by intravenous infusion of with or without liposome encapsulation is prepared under the method and according to the composition described as follows: DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS EXAMPLE 1 Oral liposomal reduced glutathione Drink or Spray 2500 mg Per Ounce
  • a lipid mixture having components lecithin and glycerin were commingled in a large volume flask and set aside for compounding
  • water, glycerin, and reduced glutathione were mixed and heated to 50 degrees C.
  • the water mixture was added to the lipid mixture while vigorously mixing with a high speed, high shear homogenizing mixer at 750-1500 rpm for 30 minutes.
  • the homogenizer was stopped and the solution was placed on a magnetic stirring plate, covered with parafilm and mixed with a magnetic stir bar until cooled to room temperature. Normally a spoilage retardant such as potassium sorbate or BHT would be added.
  • the solution would be placed in appropriate dispenser for ingestion as a liquid or administration as a spray.
  • the preferred embodiment includes the variations of the amount of glutathione to create less concentrated amounts of glutathione.
  • the methods of manufacture described in Keller et al, U.S. Pat. No. 5,891,465 are incorporated into this description.
  • the inventor, for all the examples, prefers to purchase the liposomal embodiment and application with reduced glutathione from Biozone, Inc., 580 Garcia Ave, Pittsburg, CA (USA) 94565.
  • EXAMPLE 1 A Liposomal reduced glutathione Drink or Spray 2500 mg Per Ounce or Form Suitable for Encapsulation or Gel
  • a lipid mixture having components lecithin, ethyl alcohol and glycerin were commingled in a large volume flask and set aside for compounding.
  • the lecithin is normally derived from soybeans.
  • a water mixture having water, glycerin, glutathione were mixed and heated to 50.degree. C.
  • the water mixture was added to the lipid mixture while vigorously mixing with a high speed, high shear homogenizing mixer at 750-1500 rpm for 30 minutes.
  • the homogenizer was stopped and the solution was placed on a magnetic stirring plate, covered with parafilm and mixed with a magnetic stir bar until cooled to room
  • Liposomal reduced glutathione Embodiment two of the invention includes the incorporation of the fluid liposome (such as that prepared in Example 1A) into a gelatin based capsule to improve the stability, provide a convenient dosage form, and assist in sustained release characteristics of the liposome.
  • the present embodiment relates to the use of glutathione in the reduced state encapsulated into liposomes or formulated as a preliposome formulation and then put into a capsule.
  • the capsule can be a soft gel capsule capable of tolerating a certain amount of water, a two-piece capsule capable of tolerating a certain amount of water or a two-piece capsule where the liposomes are preformed then dehydrated.
  • the liposome-capsule unit containing biologically encapsulated material can be taken in addition to orally, used for topical unit-of-use application, or other routes of application such as intra-ocular, intranasal, rectal, or vaginal.
  • the composition of examples 1 and 2 may be utilized in the encapsulated embodiment of this invention.
  • Gelatin capsules have a lower tolerance to water on their interior and exterior.
  • the usual water tolerance for a soft gel capsule is 10% on the interior.
  • the concentration of water in a liposome formulation can range from 60-90% water.
  • An essential component of the present invention is the formulation of a liposome with a relatively small amount of water, in the range of 5-10%.
  • the liposome By making the liposome in a low aqueous system, the liposome is able to encapsulate the biologically active material and the exposure of water to the inside lining of the capsule is limited. The concentration of water should not exceed that of the tolerance of the capsule for which it is intended.
  • the preferred capsule for this invention is one that can tolerate water in the 15-20% range.
  • the methods described by Keller et al, U.S. Pat. No. 6,726,924 are incorporated in this description. Components are commingled and liposomes are made using the injection method (Lasic, D., Liposomes, Elsevier, 88-90, 1993).
  • Liposomes Components are commingled and liposomes are made using the injection method (Lasic, D., Liposomes, Elsevier, 88-90, 1993).
  • liposome mixture cooled down 0.7 ml was drawn into a 1 ml insulin syringe and injected into the open-end of a soft gelatin capsule then sealed with tweezers.
  • the resulting one gram capsule contains 898 IU of Vitamin E500 mg.
  • Large scale manufacturing methods for filling gel caps, such as the rotary die process, are the preferred method for commercial applications.
  • Embodiment number three of the present invention includes the creation of liposome suspension using a self-forming, thermodynamically stable liposomes formed upon the adding of a diacylglycerol-PEG lipid to an aqueous solution when the lipid has appropriate packing parameters and the adding occurs above the melting temperature of the lipid.
  • the method described by Keller et al, U.S. Pat. No. 6,610,322 is incorporated into this description.
  • the result is a product having lecithin derived from soybeans that is hydroxylated.
  • the product is capable of very long term (14 months and greater) storage without refrigeration while remaining stable which is another unique
  • known liposome suspensions are not thermodynamic ally stable. Instead, the liposomes in known suspensions are kinetically trapped into higher energy states by the energy used in their formation. Energy may be provided as heat, sonication, extrusion, or homogenization. Since every high-energy state tries to lower its free energy, known liposome formulations experience problems with aggregation, fusion,
  • the present embodiment prefers liposome suspensions which are thermodynamically stable at the temperature of formation.
  • the formulation of such suspensions is achieved by employing a composition of lipids having several fundamental properties.
  • the lipid composition must have packing parameters which allow the formation of liposomes.
  • the lipid should include polyethyleneglycol (PEG) or any polymer of similar properties which sterically stabilizes the liposomes in suspension.
  • PEG polyethyleneglycol
  • the lipid must have a melting temperature which allows it to be in liquid form when mixed with an aqueous solution.
  • the invention includes a method of preparing liposomes. The method comprises providing an aqueous solution; providing a lipid solution, where the solution has a packing parameter measurement of P. sub. a (P. sub.
  • a references the surface packing parameter) between about 0.84 and 0.88
  • a P.sub.v references the volume packing parameter) between about 0.88 and 0.93, (See, D. D. Lasic, Liposomes, From Physics to Applications, Elsevier, p. 51 1993)
  • at least one lipid in the solution includes a polyethyleneglycol (PEG) chain; and combining the lipid solution and the aqueous solution.
  • PEG chain preferably has a molecular weight between about 300 Daltons and 5000 Daltons.
  • Kinetic energy such as shaking or vortexing, may be provided to the lipid solution and the aqueous solution.
  • the lipid solution may comprise a single lipid.
  • the lipid may comprise dioleolylglycerol-PEG-12, either alone or as one of the lipids in a mixture.
  • the method may further comprise providing an active compound, in this case glutathione (reduced); and combining the active compound with the lipid solution and the aqueous solution.
  • Intravenous doses should correspond to the amount of liposomal reduced glutathione in the earlier examples put into a suitable pharmaceutical carrier.
  • Oral and intravenous doses can be as much as 4 teaspoons a day in multiple sessions or administrations, but as previously referenced are preferably approximately 1 teaspoon twice a day.
  • the invention is applicable to neurodegenerative diseases that are related to mycotoxin-related nerve damage, which include Amyotrophic Lateral Sclerosis (ALS).
  • ALS Amyotrophic Lateral Sclerosis
  • the preferred embodiment would be to administer the combination of 200 mg of voriconazole orally per day for 2 tol6 weeks in combination with oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • neurodegenerative diseases that are related to mycotoxin-related nerve damage is to administer 200 mg of itraconazole orally per day for 2 to 16 weeks in combination with oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • the preferred combination is 200 mg of voriconazole orally per day for 2 to 16 weeks in combination with oral liposomal reduced glutathione 422 mg (1 teaspoon) twice a day.
  • doses for the pharmaceutical substances referenced on pages 5-6 above including anti-fungal medications, statins, imidazoles, triazoles, allylamines

Abstract
EP10841709.8A 2009-12-30 2010-12-30 Gestion de la myoclonie par le glutathion réduit liposomal oral Withdrawn EP2519227A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US29090309P 2009-12-30 2009-12-30
US12/649,698 US20100166846A1 (en) 2008-12-31 2009-12-30 Management of myoclonus with oral liposomal reduced glutathione
PCT/US2010/062468 WO2011082283A2 (fr) 2009-12-30 2010-12-30 Gestion de la myoclonie par le glutathion réduit liposomal oral

Publications (2)

Publication Number Publication Date
EP2519227A2 true EP2519227A2 (fr) 2012-11-07
EP2519227A4 EP2519227A4 (fr) 2014-08-06

Family

ID=44227152

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10841709.8A Withdrawn EP2519227A4 (fr) 2009-12-30 2010-12-30 Gestion de la myoclonie par le glutathion réduit liposomal oral

Country Status (2)

Country Link
EP (1) EP2519227A4 (fr)
WO (1) WO2011082283A2 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006060120A2 (fr) * 2004-11-07 2006-06-08 Guilford F Timothy Formulation liposomale pour administration par voie orale de glutathione (reduit)
WO2006105155A2 (fr) * 2005-03-29 2006-10-05 Guilford Timothy F Administration de glutathion (reduit) par intraveineuse ou encapsule dans des liposomes pour le traitement des effets du tnf-$g(a) et des symptomes viraux pseudogrippaux
WO2007030492A2 (fr) * 2005-09-06 2007-03-15 Guilford F Timothy Methode de traitement d'une infection par le virus hhv-6 et d'attenuation des symptomes lies au virus, par encapsulation liposomiale et administration de glutathion reduit

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006060120A2 (fr) * 2004-11-07 2006-06-08 Guilford F Timothy Formulation liposomale pour administration par voie orale de glutathione (reduit)
WO2006105155A2 (fr) * 2005-03-29 2006-10-05 Guilford Timothy F Administration de glutathion (reduit) par intraveineuse ou encapsule dans des liposomes pour le traitement des effets du tnf-$g(a) et des symptomes viraux pseudogrippaux
WO2007030492A2 (fr) * 2005-09-06 2007-03-15 Guilford F Timothy Methode de traitement d'une infection par le virus hhv-6 et d'attenuation des symptomes lies au virus, par encapsulation liposomiale et administration de glutathion reduit

Also Published As

Publication number Publication date
WO2011082283A2 (fr) 2011-07-07
WO2011082283A9 (fr) 2011-11-10
EP2519227A4 (fr) 2014-08-06

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