WO1985002541A1 - Chromone-2-carboxilic acid derivatives as cardiovascular agents - Google Patents
Chromone-2-carboxilic acid derivatives as cardiovascular agents Download PDFInfo
- Publication number
- WO1985002541A1 WO1985002541A1 PCT/GB1984/000395 GB8400395W WO8502541A1 WO 1985002541 A1 WO1985002541 A1 WO 1985002541A1 GB 8400395 W GB8400395 W GB 8400395W WO 8502541 A1 WO8502541 A1 WO 8502541A1
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- WO
- WIPO (PCT)
- Prior art keywords
- active ingredient
- alkyl
- amide
- cardiovascular condition
- pulmonary
- Prior art date
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- 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.
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- 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)
Abstract
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 formula (I), wherein 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 unsubsituted amide hereof, or of an anti-leukotrine compound as herein defined (as active ingredient), to a human patient suffering from the cardiovascular condition.
Description
CHROMONE-2-CARBOXILIC ACID DERIVATES AS CARDIOVASCULAR AGENTS
This invention relates to a new therapeutic method. In 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.
Surprisingly we have now found that a selected group of the compounds of US Patent 3,686,412 and some anti-leukotriene compounds are useful in the treatment of a variety of cardiovascular conditions, e.g. the cardiovascular sequelae of hypoxia.
At present the main effective treatment for the cardiovascular sequelae of hypoxia is to administer oxygen for 15 or more hours per day. However, the administration of oxygen for such protracted periods is very inconvenient for the patient, and is expensive.
According to the invention there is provided 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,
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). Esters which may be mentioned include simple alkyl esters (e.g. methyl, ethyl, propyl, isopropyl, butyl and tertiary butyl esters) and 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 -(CH2)5- and -CH2CHOHCH2-.
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). This can be established by use of the isolated guinea-pig ileum preparation (Augstein et al. Nature, New Biology, 1973, 245, 215) in which contractions induced by SRS-A (i.e. leukotrienes C4, D4 and E4) will be expected to be antagonised by the compound at concentrations of less than 1 μg/ml.
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. We prefer the compounds of
British Patent Specifications Nos 1,384,530; 1,583,691 and especially those of European Patent Applications Nos 80300565.1 and 82.201368.6. Specifically we prefer 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid, and 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-propanoic acid, and the pharmaceutically acceptable salts, e.g. the sodium or lysine salts, of either thereof. The compound having anti-leukotriene activity may also have lipoxygenase inhibitory activity, i.e. be able to block the production of lipoxygenase products from rat basophilic leukaemia cells (Casey et al, Prostaglandins 25,1,1983). The compound having anti-leukotriene activity may also have cyclo-oxygenase inhibitory activity, i.e. be able to block the production of prostaglandin E2 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. the treatment of asthma, exert their activity in an entirely different manner to sodium cromoglycate. Thus anti SRS-A compounds antagonise the effects of slow-reacting substance of
anaphylaxis (SRS-A) (leukotrienes) once it has been released from whatever source, whereas 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. When the drug is given by infusion the infusion may be continuous over the period of treatment or may be intermittent, e.g. for periods of about two hours.
In order to produce suitable compositions the drug may be worked up with inorganic or organic pharmaceutically acceptable adjuvants, carriers or excipients. The type of formulation will vary with the mode of administration to be used. Examples of 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. those who had raised pulmonary artery pressures before the operation, particularly in mitral valve replacement subjects) there is a reduced cardiac performance with high pulmonary vascular resistance for some hours after the operation. During the operation the lungs are not normally ventilated or perfused and may have become hypoxic.
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.
We believe that the drugs are effective in that they have a direct action on the pulmonary arterial response to hypoxia.
The anti-SRS-A compounds, and particularly the preferred compounds, are advantageous in that they exert their effect without affecting systemic blood pressure to a corresponding degree.
Claims
1. A method for the treatment of a cardiovascular condition which method comprises administration of an effective amount of a compound of the formula I,
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 hereinbefore defined (as active ingredient), to a human patient suffering from the cardiovascular condition.
2. A method according to Claim 1, wherein the active ingredient also has lipoxygenase inhibitory activity.
3. A method according to Claim 1 or 2, wherein the active ingredient also has cyclo-oxygenase inhibitory activity.
4. A method according to Claim 1, wherein the active ingredient is sodium cromoglycate.
5. A method according to Claim 1, wherein the active ingredient is 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
6. A method according to Claim 1, wherein the active ingredient is 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-propanoic acid or a pharmaceutically acceptable salt thereof.
7. A method according to any one of the preceding claims, wherein a daily dosage of from 1 to 400mg of active ingredient is administered.
8. A method according to any one of the preceding claims, wherein the active ingredient is administered by infusion, by inhalation or orally.
9. A method according to any one of the preceding claims, wherein the cardiovascular condition involves pulmonary artery hypertension.
10. A method according to any one of the preceding claims, wherein the cardiovascular condition is cor pulmonale, persistent neonatal pulmonary hypertension, adult respiratory disease syndrome, cyanotic congentinal heart disease, myocardial infarct, hypoxic pulmonary oedema, destructive parenchymous lung disease, primary alveolar hypoventilation, hypoxia induced cerebral vasoconstriction, sleep apnoea syndrome or is in a patient suffering from chest wall deformity or who has undergone cardio-pulmonary by-pass surgery.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8423907A IT8423907A0 (en) | 1983-12-06 | 1984-12-05 | TREATMENT METHOD. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB838332450A GB8332450D0 (en) | 1983-12-06 | 1983-12-06 | Method of treatment |
| GB8332450 | 1983-12-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1985002541A1 true WO1985002541A1 (en) | 1985-06-20 |
Family
ID=10552857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1984/000395 WO1985002541A1 (en) | 1983-12-06 | 1984-11-19 | Chromone-2-carboxilic acid derivatives as cardiovascular agents |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0163683A1 (en) |
| AU (1) | AU3611784A (en) |
| GB (1) | GB8332450D0 (en) |
| WO (1) | WO1985002541A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9265749B2 (en) | 2014-02-10 | 2016-02-23 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| WO2017027402A1 (en) | 2015-08-07 | 2017-02-16 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
| US10265267B2 (en) | 2016-08-31 | 2019-04-23 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
| US10561635B2 (en) | 2016-10-07 | 2020-02-18 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
| EP3725311A1 (en) | 2014-02-10 | 2020-10-21 | Respivant Sciences GmbH | Methods for the treatment of lung diseases with mast cell stabilizers |
| WO2021094296A1 (en) | 2019-11-12 | 2021-05-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of mast cell stabilizer for the treatment of heart failure with preserved ejection fraction |
-
1983
- 1983-12-06 GB GB838332450A patent/GB8332450D0/en active Pending
-
1984
- 1984-11-19 EP EP19840904149 patent/EP0163683A1/en 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 (6)
| Title |
|---|
| CHEMICAL ABSTRACTS, Vol. 85, 1976 (Columbus, Ohio, US) J. ROSS et al.: "Increased Vascular Permeability During Passive Peritoneal Anaphylaxis in the Rat. The Effects of Disodium-Cromoglycate and a Nitroindanedione", see page 491, Abstract No. 18836s, & Int. Arch. Allergy Appl. Immunol. 1975, 51(2), 226 * |
| CHEMICAL ABSTRACTS, Vol. 92, 1980 (Columbus, Ohio, US) F. RENGO et al.: "Effects of Disodium Chromoglycate on Hypoxic Pulmonary Hypertension in dogs", see page 82, Abstract No. 15759c, & J. Pharmacol. Exp. Ther. 1979, 211(3), 686-9 * |
| CHEMICAL ABSTRACTS, Vol. 92, 1980 (Columbus, Ohio, US) F. RENGO et al.: "Effects of Disodium Chromoglycate on Hypoxic Pulmonary Hypertension in dogs: Possible Mechanisms of Action", see page 39, Abstract No. 5186w, & Riv. Pharmacol. Ter. 1979, 10(2), 155-61 * |
| CHEMICAL ABSTRACTS, Vol. 92, 1980 (Columbus, Ohio, US) M. DIXON et al.: "The Effects of Sodium Cromoglycate on Lung Irritant Receptors and left Ventricular Cardiac Receptors in the Anesthetized Dog", see page 30, Abstract No. 140539g; & Br. J. Pharmacol. 1979, 67(4), 569-74 * |
| Journal of Medicinal Chemistry, Vol. 17, No. 5, 1974 (Washington, US) M. MARDLE et al.: "Bronchodilators Giving Reduced Cardiovascular Effects. Relative Biological Activities of the four Isomers of 1-(3-4-Dihydroxyphenyl)-2-Isopropylaminobutanol", pages 513-516, see page 515, table II * |
| Research Disclosure, No. 208, August 1981 (Havant Hampshire, GB) page 304, Abstract No. 20801, "A Method for the Prevention of Inhibition of Platelet Aggregation" * |
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| US10398673B2 (en) | 2014-02-10 | 2019-09-03 | Respivant Services GmbH | Mast cell stabilizers treatment for systemic disorders |
| US10835512B2 (en) | 2014-02-10 | 2020-11-17 | Respivant Sciences Gmbh | Methods of treating respiratory syncytial virus infections |
| US9707206B2 (en) | 2014-02-10 | 2017-07-18 | Patara Pharma, LLC | Mast cell stabilizers treatment for systemic disorders |
| US9962363B2 (en) | 2014-02-10 | 2018-05-08 | Patara Pharma, LLC | Mast cell stabilizers treatment for systemic disorders |
| US9968586B2 (en) | 2014-02-10 | 2018-05-15 | Patara Pharma, LLC | Mast cell stabilizers treatment for systemic disorders |
| US10238628B2 (en) | 2014-02-10 | 2019-03-26 | Respivant Sciences Gmbh | Mast cell stabilizers treatment for systemic disorders |
| EP3725311A1 (en) | 2014-02-10 | 2020-10-21 | Respivant Sciences GmbH | Methods for the treatment of lung diseases with mast cell stabilizers |
| EP3653207A1 (en) | 2014-02-10 | 2020-05-20 | Respivant Sciences GmbH | Mast cell stabilizers treatment for systemic disorders |
| US9265749B2 (en) | 2014-02-10 | 2016-02-23 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10265296B2 (en) | 2015-08-07 | 2019-04-23 | Respivant Sciences Gmbh | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10391078B2 (en) | 2015-08-07 | 2019-08-27 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
| US10596146B2 (en) | 2015-08-07 | 2020-03-24 | Respivant Sciences Gmbh | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
| WO2017027402A1 (en) | 2015-08-07 | 2017-02-16 | Patara Pharma, LLC | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
| US10463613B2 (en) | 2016-08-31 | 2019-11-05 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
| US10265267B2 (en) | 2016-08-31 | 2019-04-23 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
| US10561635B2 (en) | 2016-10-07 | 2020-02-18 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
| US10583113B2 (en) | 2016-10-07 | 2020-03-10 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
| WO2021094296A1 (en) | 2019-11-12 | 2021-05-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of mast cell stabilizer for the treatment of heart failure with preserved ejection fraction |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0163683A1 (en) | 1985-12-11 |
| GB8332450D0 (en) | 1984-01-11 |
| AU3611784A (en) | 1985-06-26 |
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