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
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom

Definitions

• This invention relates to a new therapeutic method.
• US Patent No 3,686,412 there are described a large number of bis-chromonyl compounds and their use in the treatment of asthma. These compounds are described as being administered preferably by way of inhalation.
• a number of compounds are also known as having anti SRS-A or anti-leukotriene activity, and these compounds have been described as being useful in the treatment of various allergic airways diseases notably asthma.
• a method of treatment of a cardiovascular condition e.g. the cardiovascular sequelae of hypoxia, which method comprises administration of an effective amount of a compound of the formula I,
• X is a polymethylene chain containing 3 to 7 carbon atoms inclusive, which chain may be substituted by an -OH group, or a pharmaceutically acceptable salt, alkyl C 1 to 10 ester, mono-alkyl C 1 to 10 amide, di-alkyl C 1 to 10 amide or unsubstituted amide thereof, or of an anti-leukotriene compound as hereinafter defined (as active ingredient), to a human patient suffering from the cardiovascular condition.
• Suitable pharmaceutically acceptable salts of the compounds of formula I include, for example, ammonium salts, alkali metal salts (e.g. sodium, potassium and lithium), alkaline earth metal salts (e.g. magnesium and calcium), and salts with organic amines (e.g. mono di- or tri-alkyl C 1 to 6 amines, piperidine, and trialkanol C 1 to 6 amine salts).
• alkali metal salts e.g. sodium, potassium and lithium
• alkaline earth metal salts e.g. magnesium and calcium
• organic amines e.g. mono di- or tri-alkyl C 1 to 6 amines, piperidine, and trialkanol C 1 to 6 amine salts.
• Esters which may be mentioned include simple alkyl esters (e.g.
• amides which may be mentioned include simple amides (for example amides with ammonia and lower alkylamines such as methylamine, ethylamine etc).
• Specific examples of the group X are groups of the formula -(CH 2 ) 5 - and -CH 2 CHOHCH 2 -.
• the chain -O-X-O- in formula I may link different or corresponding positions on the chromone nuclei.
• a specific compound of formula I which may be used in this invention is 1,3-bis (2-carboxychromon-5-yloxy)-2- hydroxypropane. This compound may be used in the form of its pharmaceutically acceptable, e.g. its di-sodium, salt which is commonly known as sodium cromoglycate. It may also be used in the form of its di-ethyl ester, or of its simple amide derived from ammonia.
• An anti SRS-A (anti-leukotriene) compound is able to antagonise the actions of SRS-A on an end-organ (e.g. bronchial or intestinal smooth muscle).
• an end-organ e.g. bronchial or intestinal smooth muscle.
• the anti-leukotriene compounds to be used in the present invention are those of British Patent Specifications Nos 1,384,530; 1,583,691 and European Patent Applications Nos 80300565.1; 81201386.0; 82200312.5 and 82201368.6.
• the compound having anti-leukotriene activity may also have cyclo-oxygenase inhibitory activity, i.e. be able to block the production of prostaglandin E 2 from the microsomal fraction of bovine seminal vesicles (Mitchell et al, Biochem. Soc. Transactions 12, 839,1984).
• Compounds which have anti SRS-A (anti-leukotriene) activity while they have been suggested for the same uses as sodium cromoglycate, e.g.
• SRS-A slow-reacting substance of anaphylaxis
• sodium cromoglycate and its biologues exert their activity by preventing the release of SRS-A and other mediators of anaphylaxis from mast cells.
• the administration may be by any convenient route, for example oral inhalation; by infusion, e.g. for use in acute conditions; orally or rectally.
• infusion e.g. for use in acute conditions
• rectally e.g. for use in acute conditions
• the infusion may be continuous over the period of treatment or may be intermittent, e.g. for periods of about two hours.
• the drug may be worked up with inorganic or organic pharmaceutically acceptable adjuvants, carriers or excipients.
• suitable adjuvants are, for inhalation compositions, dry powder diluents, e.g. lactose; water for nebuliser solutions, and aerosol propellents and surfactants for pressurised aerosol compositions.
• Solutions e.g. sterile aqueous solutions, may be used for intravenous administration. The solutions preferably contain less than 10% w/w and more than 1% w/w of the active ingredient.
• the drug may, if desired, be used in a specific form, e.g. having a mass median diameter of less than 10 microns.
• the drug may also be used for inhalation in admixture with a bronchodilator, eg such as described in British Patent Specification Number 2,077,100A.
• the dosage to be administered will of course vary with the compound used, the method of administration, the condition to be treated and with its severity. However, in general, a dosage of from about 1 to 50, and more preferably 5 to 40 mg of the drug administered 1 to 8, and preferably 1 to 4, times a day (i.e. a daily dosage of from 1 to 400, and preferably 5 to 160mg) is satisfactory.
• the method of the invention is applicable to patients who have an allergic component to their condition, but more particularly to those who do not.
• the primary cardiovascular complication in hypoxia is the development of pulmonary artery hypertension, which in turn is the principal cause of right ventricular enlargement and failure (cor pulmonale).
• the pulmonary arterial hypertension may be severe and moreover the right ventricle is often faced with a pulmonary artery pressure which has risen rapidly in the course of an intercurrent acute illness.
• the method of the invention may also be used to treat other cardiovascular conditions which are the sequelae of hypoxia, e.g. persistent neonatal pulmonary hypertension (or persistent foetal circulation), a condition in which the pulmonary arteries fail to dilate soon enough after birth; adult respiratory disease syndrome, a condition which manifests itself as pulmonary oedema with normal filling pressures in the left heart, greatly reduced pulmonary compliance, abnormal vasomotor activity and severe hypoxaemia (this syndrome may result from trauma, shock or endotoxaemia); or cyanotic congenital heart disease, a condition in which hypertension is a frequent complication.
• the method of the invention may also be used in patients who have undergone cardio-pulmonary by-pass surgery in which in some patients (e.g.
• the method of the invention may also be used to treat patients with myocardial infarcts due to hypoxia in which lipoxygenase products of arachidonic acid metabolism such as leukotrienes may be involved.
• the method of the invention is also applicable to patients suffering from acute hypoxic pulmonary oedema (for example mountain sickness); destructive parenchymous lung disease such as tuberculosis, bronchiectasis or fibrosing alveolitis; chest wall deformities such as severe kyphoscolioses; primary alveolar hypoventilation; hypoxia induced cerebral vasoconstriction; and sleep apnoea syndrome.
• acute hypoxic pulmonary oedema for example mountain sickness
• destructive parenchymous lung disease such as tuberculosis, bronchiectasis or fibrosing alveolitis
• chest wall deformities such as severe kyphoscolioses
• primary alveolar hypoventilation a primary alveolar hypoventilation
• hypoxia induced cerebral vasoconstriction and sleep apnoea syndrome.
• the anti-SRS-A compounds are advantageous in that they exert their effect without affecting systemic blood pressure to a corresponding degree.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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Cited By (5)

Families Citing this family (2)

• 1983
  • 1983-12-06 GB GB838332450A patent/GB8332450D0/en active Pending
• 1984
  • 1984-11-19 EP EP19840904149 patent/EP0163683A1/de not_active Withdrawn
  • 1984-11-19 WO PCT/GB1984/000395 patent/WO1985002541A1/en unknown
  • 1984-11-19 AU AU36117/84A patent/AU3611784A/en not_active Abandoned

Non-Patent Citations (1)

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