Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/44—Elemental carbon, e.g. charcoal, carbon black
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/12—Drugs for disorders of the urinary system of the kidneys
• • 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
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• • 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
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
  • A61P25/16—Anti-Parkinson drugs
• • 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
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

• the present invention relates to the use of carbon monoxide (CO) as a biomarker and therapeutic agent of heart, lung, liver, spleen, brain, skin and kidney diseases and other conditions and disease states including, for example, asthma, emphysema, bronchitis, adult respiratory distress syndrome, sepsis, cystic fibrosis, pneumonia, interstitial lung diseases, idiopathic pulmonary diseases, other lung diseases including primary pulmonary hypertension, secondary pulmonary hypertension, cancers, including lung, larynx and throat cancer, arthritis, wound healing, Parkinson's disease, Alzheimer's disease, peripheral vascular disease and pulmonary vascular thrombotic diseases such as pulmonary embolism.
• CO carbon monoxide
• a therapeutic gas comprising low concentrations (i.e., concentrations ranging from about 1 ppb (part per billion) to about 3,000 ppm (preferably above about 0.1 ppm within this range) of the gas, preferably about 1 ppm to about 2,800 ppm, more preferably about 25 ppm to about 750 ppm, even more preferably about 50 ppm to about 500 ppm, e.g., about 250 ppm) of carbon monoxide is an extremely effective method for delaying the onset of, inhibiting or reversing the effects of oxidative stress in a patient. This is an unexpected result. It is noted here that in the method of the present invention, an amount of carbon monoxide in the therapeutic gaseous composition which is in excess of 0.3% may sometimes be used, depending upon the condition or disease state to be treated.
• a carbon monoxide composition may be a gaseous carbon monoxide composition.
• compressed or pressurized gas useful in the methods of the invention can be obtained from any commercial source, and in any type of vessel appropriate for storing compressed gas.
• compressed or pressurized gases can be obtained from any source that supplies compressed gases, such as oxygen, for medical use.
• the pressurized gas including carbon monoxide used in the methods of the present invention can be provided such that all gases of the desired final composition (e.g., CO, CO 2 , O 2 , N 2 ) are mixed in the same vessel.
• the methods of the present invention can be performed using multiple vessels containing individual gases.
• a single vessel can be provided that contains carbon monoxide, with or without other gases, the contents of which can be optionally mixed with room air or with the contents of other vessels, e.g., vessels containing oxygen, nitrogen, carbon dioxide, helium, compressed air, or any other suitable gas or mixtures thereof.
• the amount of nitrogen in the gaseous composition is about 79% by weight
• the amount of oxygen is about 21% by weight
• the amount of carbon monoxide is about 0.0001% to about 0.25% by weight, preferably at least about 0.001%, e.g., at least about 0.005%, 0.010%, 0.02%, 0.025%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08%, 0.10%, 0.15%, 0.20%, 0.22%, or 0.24% by weight of carbon monoxide.
• a carbon monoxide composition may also be a liquid carbon monoxide composition.
• a liquid can be made into a carbon monoxide composition by any method known in the art for causing gases to become dissolved in liquids.
• the liquid can be placed in a so-called "CO 2 incubator" and exposed to a continuous flow of carbon monoxide, preferably balanced with carbon dioxide, until a desired concentration of carbon monoxide is reached in the liquid.
• carbon monoxide gas can be "bubbled” directly into the liquid until the desired concentration of carbon monoxide in the liquid is reached. The amount of carbon monoxide that can be dissolved in a given aqueous solution increases with decreasing temperature.
• an appropriate liquid may be passed through tubing that allows gas diffusion, where the tubing runs through an atmosphere comprising carbon monoxide (e.g., utilizing a device such as an extracorporeal membrane oxygenator).
• the carbon monoxide diffuses into the liquid to create a liquid carbon monoxide composition.
• the liquid can be any liquid known to those of skill in the art to be suitable administration to a patient (see, for example, Oxford Textbook of Surgery, Morris and Malt, Eds., Oxford University Press (1994)).
• the liquid will be an aqueous solution.
• a patient can be treated with a carbon monoxide composition by any method known in the art of administering gases and/or liquids to patient.
• Carbon monoxide compositions can be administered to a patient diagnosed with, or determined to be at risk, for example, for emphysema, bronchitis, arthritis, cystic fibrosis, pneumonia, interstitial lung disease, Parkinson's disease, Alzheimer's disease, or inflammation of the kidneys, spleen, or skin; or to promote wound healing, e.g., healing of skin wounds not associated with surgery.
• a carbon monoxide-containing gas mixture is prepared as above to allow passive inhalation by the patient using a facemask or tent.
• the concentration inhaled can be changed and can be washed out by simply switching over to 100% O 2 .
• Monitoring of carbon monoxide levels would occur at or near the mask or tent with a fail-safe mechanism that would prevent too high of a concentration of carbon monoxide from being inhaled.
• the skin and underlying joints can be treated topically with a gaseous composition by, for example, exposing the affected skin to the gaseous composition in a normobarometric chamber (described above), and/or by blowing the carbon monoxide composition directly onto the skin.
• Liquid carbon monoxide compositions can also be administered topically to a patient's organs.
• Liquid forms of the compositions can be administered by any method known in the art for administering liquids to patients.
• liquid compositions can be applied directly to the interior and/or exterior of the body to treat a patient's organs.
• inflammation is used to describe the fundamental pathological process consisting of a dynamic complex of cytologic and histologic reactions that occur in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical or biologic agent, including the local reactions and resulting morphologic changes, the destruction or removal of the injurious material, and the responses that lead to repair and healing.
• the term includes various types of inflammation such as acute, allergic, alterative (degenerative), atrophic, catarrhal (most frequently in the respiratory tract), croupous, fibrinopurulent, fibrinous, immune, hypcrplastic or proliferative, subacute, serous and seiofibrinous.
• Parkinson's disease refers to "an idiopathic, slowly progressive, degenerative CNS disorder characterized by slow and decreased movement, muscular rigidity, resting tremor, and postural instability.” (The Merck Manual of Diagnosis and Therapy, 17 th Edition, Section 14, Chapter 179).
• the term “Alzheimer's disease” refers to a disease characterized by "a progressive, inexorable loss of cognitive function associated with an excessive number of senile plaques in the cerebral cortex and subcortical gray matter, which also contains b-amyloid and neurofibrillary tangles consisting of tau protein," (The Merck Manual of Diagnosis and Therapy, 17 l Edition, Section 14, Chapter 171).
• the present invention also relates to the use of CO as a preservative for storing organs or tissues to be used in transplants. It is an unexpected result that the inclusion of low dosage CO in the mediumin which organs to be transplanted are stored will substantially reduce the likelihood of oxidative damage to the organs during storage and substantially enhance the storage time that organs to be transplanted may be safely stored without suffering irreversible oxidative damage.
• an effective amount of CO is bubbled into storage medium cither before or preferably when an organ is first placed in the media or shortly thereafter.
• CO may also be used to enhance the storage stability of organs which have been stored for some time in media, but in those instances, oxidative damage may have become irreversible, thus limiting the intended effect.

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• Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Neurosurgery (AREA)
• Neurology (AREA)
• Biomedical Technology (AREA)
• Epidemiology (AREA)
• Inorganic Chemistry (AREA)
• Rheumatology (AREA)
• Immunology (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Urology & Nephrology (AREA)
• Pulmonology (AREA)
• Hospice & Palliative Care (AREA)
• Psychology (AREA)
• Physical Education & Sports Medicine (AREA)
• Pain & Pain Management (AREA)
• Psychiatry (AREA)
• Dermatology (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Investigating Or Analysing Biological Materials (AREA)

Applications Claiming Priority (1)

Publications (2)

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• 2002
  • 2002-05-09 JP JP2004503016A patent/JP2005532314A/ja active Pending
  • 2002-05-09 CN CNA028292995A patent/CN1638781A/zh active Pending
  • 2002-05-09 RS YUP-969/04A patent/RS96904A/sr unknown
  • 2002-05-09 WO PCT/US2002/014836 patent/WO2003094932A1/en not_active Ceased
  • 2002-05-09 KR KR10-2004-7018082A patent/KR20040106515A/ko not_active Ceased
  • 2002-05-09 EP EP02807413A patent/EP1501523A4/de not_active Withdrawn
  • 2002-05-09 MX MXPA04011113A patent/MXPA04011113A/es active IP Right Grant
  • 2002-05-09 BR BR0215717-9A patent/BR0215717A/pt not_active Application Discontinuation
  • 2002-05-09 UA UA20041210106A patent/UA84402C2/ru unknown
  • 2002-05-09 AU AU2002308676A patent/AU2002308676B2/en not_active Ceased
  • 2002-05-09 CA CA002484770A patent/CA2484770A1/en not_active Abandoned
  • 2002-05-09 EA EA200401478A patent/EA200401478A1/ru unknown
• 2004
  • 2004-11-09 NO NO20044865A patent/NO20044865L/no not_active Application Discontinuation

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