GB1582362A - Cromoglycic acid salts and compositions - Google Patents
Cromoglycic acid salts and compositions Download PDFInfo
- Publication number
- GB1582362A GB1582362A GB11390/77A GB1139077A GB1582362A GB 1582362 A GB1582362 A GB 1582362A GB 11390/77 A GB11390/77 A GB 11390/77A GB 1139077 A GB1139077 A GB 1139077A GB 1582362 A GB1582362 A GB 1582362A
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- GB
- United Kingdom
- Prior art keywords
- salt
- bis
- yloxy
- propan
- carboxychromon
- 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.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
Abstract
The medicament comprises either a salt of 1,3-bis(2-carboxychromon-5-yloxy)-2-propanol with a basic compound containing a six-membered nitrogenous heterocycle and manifesting H1 receptor-antagonist antihistaminic properties, or a mixture comprising (a) one or more compounds chosen from 1,3-bis(2-carboxychromon-5-yloxy)-2-propanol and its pharmaceutically acceptable salts and (b) one or more antihistaminics containing a six-membered nitrogenous heterocycle and manifesting H1 receptor-antagonist properties.
Description
(54) CROMOGLYCIC ACID SALTS AND COMPOSITIONS
(71) We, FISONS LIMITED, a British Company, of Fison House, 9 Grosvenor Street,
London WIX OAH do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:
This invention relates to new compounds, mixtures and methods for their preparation.
A variety of anti-histamines have been known for many years for use in the palliative treatment of allergic conditions. However the anti-histamines have, in the vast majority of cases been administered systemically, e.g. as elixirs, tablets, capsules etc. Furthermore most of the anti-histamines have unwanted side effects, e.g. have a sedative action, which causes their use in high dosage not to be recommended when activities, such as driving a motor car, are to be undertaken.
Disodium cromoglycate has also been recommended for use in the treatment of allergic conditions and in particular of asthma and allergic rhinitis. By way of contrast to the anti-histamines disodium cromoglycate has been used prophylactically and has not in general been recommended for use in a curative sense, i.e. during an attack of the allergy.
We have now found that mixtures of disodium cromoglycate with certain anti-histamines, and salts of 1*3-bis(2-carboxychromon-5-yl-oxy)propan-2-ol with those antihistamines, possess the advantage that they are both palliative and prophylactic, are more effective, produce less side effects, can be used at lower doses, can be administered directly to the site of the allergy. are longer acting. are more stable, or possess other desirable properties as compared to antihistamines when used on their own, disodium cromoglycate when used on its own, or certain other mixtures when tested in certain pharmacological models relevant to the nasal or ocular manifestations of allergy.
According to the invention we provide a salt of 1,2-bis(2-carboxychromon-5yloxy)propan-2-ol with a basic compound which has anti-histamine H, receptor antagonist properties, and which contains a 6 membered nitrogen heterocyclic ring.
The basic compound which has anti-histamine H1 receptor antagonist properties may be, for example, trimeprazine, cyproheptadine, pheniramine, mepyramine, chlorpheniramine, brompheniramine, dimethindene, carbinoxamine, tripelennamine or preferably triprolidine. We prefer the salt to be at least 1%, and preferably at least 4%, w/v soluble in water.
The salt may be made by a metathetical process, e.g. by reacting a suitable salt, such as the sodium salt, of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol with an appropriate salt, e.g. the hydrochloride, of the antihistamine. However the salt is preferably produced by reacting the free acid, 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol with the free antihistamine base, as such a process does not produce a bi-product inorganic salt. The reaction may be carried out in a solvent which is inert under the reaction conditions. The solvent is preferably one in which desired salt is soluble, e.g. water or an alkanol such as ethanol. The desired salt may be isolated and purified, for example by crystallisation or by freeze drying.
According to the invention we therefore provide the salt when not in solution, e.g. the salt when in a substantially dry form, or when in admixture with insufficient liquid, e.g.
water, to dissolve it all.
The salt may, if desired, be used in conjunction with one or more other salts of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol, notably the disodium salt thereof.
According to our invention therefore we also provide a pharmaceutical mixture comprising (a) one or more of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-9l, or a pharmaceutically acceptable salt thereof, (herein referred to collectively as 'active ingredient') in combination with (b) one or more anti-histamines having H1 receptor antagonist properties and which contains a 6 membered nitrogen heterocyclic ring.
We prefer to use the di-sodium salt of 1,3-bis(2-carboxy-chromon-5-yloxy)propan-2-ol, which is commonly known as disodium cromoglycate, or a salt with a basic compound which has antihistamine H1 receptor antagonist properties and which contains a 6 membered nitrogen heterocyclic ring, as active ingredient.
The anti-histamine may be any of those described above or a pharmaceutically acceptable salt thereof, e.g. the hydrochloride, tartrate or maleate thereof.
The ratio of active ingredient and antihistamine in the composition will vary with the particular active ingredient and antihistamine used and the specific purpose for which the composition is intended. When the active ingredient is itself a salt of 1,2-bis(2carboxychromon-5-yloxy)propan-2-ol with an antihistamine it may be necessary to use, none, or only a very small proportion of 'free' anithistamine (i.e. of the basic antihistamine itself or of a salt of the antihistamine other than with 1,3-bis(2-carboxychromon-5yloxy)propan-2-ol).
We prefer the composition to contain only one active ingredient and only one antihistamine.
A suitable daily dose of active ingredient for most purposes is in the range 1 to 100 mg and preferably 1 to 20 mg, (measured as disodium cromoglycate).
A suitable daily dosage of antihistamine will vary with the antihistamine and is in the following ranges:
Cyproheptadine (as the hydrochloride) 0.1-40 mg
Trimeprazine (as the tartrate) 0.1-40 mg
Pheniramine (as the maleate) 0.1-50 mg
Mepyramine (as the maleate) 0.1-100 mg
Chlorpheniramine (as the maleate) 0.1-20 mg
Brompheniramine (as the maleate) 0.1-8 mg
Dimethindine (as the maleate) 0.1-6 mg
Carbinoxamine (as the maleate) 0.1-8 mg
Tripelennamine (as the hydrochloride) 0.1-100 mg
Triprolidine (as the hydrochloride) 0.1-7.5 mg
A preferred daily dosage of the antihistamine is from 0.1 to 5 mg, and more preferably from 0.5 to 2 mg.
The composition may be administered as divided doses from 1 to 6, and preferably from 2 to 4, times per day. Each dose may comprise one or more unit doses.
The specific ratios of particular active ingredients and particular antihistamines in any composition according to the invention can be calculated from the above daily dosages. We prefer a composition containing from 1,000 to 0.2 parts by weight, and more preferably from 40 to 0.5 parts by weight of active ingredient (measured as disodium cromoglycate) for each part by weight of anithistamine. We particularly prefer a composition containing disodium cromoglycate and triprolidine in a weight ratio of about 20:1.
The salts and/or mixtures of the invention may be used for the treatment of a condition of the eye, nose or skin which condition has an allergic component, e.g. allergic rhinitis, by administration of a salt and/or mixture to an individual mammal, e.g. human, suffering from such a condition. The administration is preferably to the nose.
Conditions of the outer eye which may be mentioned include vernal catarrh (vernal kerato-conjunctivitis) and marginal corneal ulceration or infiltration. Other conditions which may be treated include the ocular effects of hay fever, 'allergic eyes' where the allergen is known or unknown and spring/summr conjunctivitis. This latter term is used to mean allergic disorders of the eyes occurring in the spring and summer where an external allergen plays a part in the disorder. Further conditions of the eye which may be mentioned are irritable eye' or 'non-specific conjunctivitis', herpex simpler keratitis and conjunctivitis, herpes zoster keratitis and conjunctivitis, adenovirus infections, phlyctenular conjunctivitis, corneal homograft rejection,. trachoma, anterior uvetis and drug sensitivity.
Conditions of the nose which may be mentioned include seasonal rhinitis, e.g. hay fever; perennial rhinitis, nasal polyps and allergic manifestations of the nasopharynx.
Dermatoses which may be treated include those involving skin mast cells and/or antibody/antigen reactions and include eczemas and especially atopic eczema, drug eruptions, psoriasis, dermatitis herpetiformis, pemphigus and chronic skin ulcers, notably those affecting man in tropical climates.
When sequential or simultaneous administration of active ingredient and antihistamine is used the ratios and dosages of the active ingredient and antihistamine are as described above with respect to the mixtures. We prefer the administration of the active ingredient and the antihistamine to be within about 10 minutes of one another.
The invention therefore also provides a pharmaceutical package comprising at least one dose of active ingredient and at least one dose of the antihistamine. The doses are unit doses and are arranged in the package in a particular order together with written or printed indications or directions, the indications or directions and the manner of packing being such as to provide guidance in relation to and to facilitate the taking of a dose of active ingredient and a dose of the antihistamine in a particular order, e.g. a dose of the former before a dose of the latter. The package is preferably a sealed package and may comprise a tube, box or chart in or on which the doses are packed. The doses are preferably suitable for nasal administration, e.g. spray formulations for spraying into the nose, and preferably contain the doses of active ingredient and the antihistamine in the ratios set out above for the compositions.
In order to produce suitable compositions the salt, the active ingredient and the antihistamine, either separately or as a mixture thereof, are worked up with an organic or inorganic pharmaceutically acceptable adjuvant or excipient.
We prefer compositions which are designed to be administered to the eye or nose, e.g.
aqueous solutions containing, for example up to 10% by weight of the salt or mixure according to the invention. The compositions may also contain one or more preservatives, e.g. benzylkonium chloride and/or phenylethyl alcohol. The preservatives may be present in up to about 2.0% w/v and may, for example, comprise from about 0.002% w/v to 0.05% w/v of benzylkonium chloride and/or from about 0.1% to 1.0% w/v of phenylethyl alcohol, or from about 0.0005% to 0.005% of phenyl mercuric nitrate, or from about 0.005 to 0.05% of thiomersal. or from about 0.2 to 1.0% of chlorbutol. The composition may also contain a sequestering agent, e.g. disodium edetate. The sequestering agent may be present in from about 0.005% to 0.2% w/v. The pH of the composition may be controlled by inclusion of one or more buffers, e.g. monosodium phosphate or di-sodium phosphate. The pH of the composition may be adjusted to be compatible with physiological solutions and/or to improve the solubility of the ingredients or the stability of the composition. The composition may also include an agent which increases its viscosity, e.g. certain cellulose derivatives or a polyvinyl alcohol.
Compositions to be administered to the eye or nose are preferably isotonic.
Alternatively we provide powder compositions for administration to the nose and preferably comprising fine particles of the antihistamine and/or of the salt of 1,3-bis(2carboxychromon-5-yloxy)propan-2-ol.
The active ingredient and the antihistamine may, if desired, be used in a specific form, e.g. having a mass median diameter of less than 10 microns.
The invention is illustrated. but in no way limited by the following Examples.
EXAMPLE 1
Chlorpheniramine salt of 1 ,3-his(2-carboxydironion-5-yloxy) -propan-2-ol 1-(p-Chlorophenyl)-1-(2-pyridyl)-3-N,N-dimethylpropylamine maleate (3.7 parts) was dissolved in water, basified using 10% NaOH, extracted into ether and dried (Na2SO4).
The drying agent and ether were removed, water was added followed by 1,3-bis(2carboxychromon-5-yloxy)propan-2-ol (2.3 parts). This mixture was stirred for 2 hours, washed with ether, and traces of ether were removed before the product was isolated from the aqueous solution by freeze drying.
Analysis:
Found: C, 60.0 H, 5.9 N, 4.9
Calc for C23H16O11.C16H19ClN2).8H20: C, 60.5 H, 6.5 N, 5.1%
EXAMPLE 2
Triprolidine salt of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol 1.2g of trans-2-[3-(1-pyrrolidinyl)-1-p-tolypropenyl]-pyridine hydrochloride were dissolved in 50 ml of water and basified with 10% NaOH. The free base was extracted into ether and dried over magnesium sulphate. Filtration and evaporation of the ether left the residual free base. To this was added a slight excess of 1,3-bis(2-carboxychromon-5yloxy)propan-2-ol (0.9g) and water (20 ml). After stirring for 2 hour insolubles were removed by filtration and the salt was isolated from the filtrate by freeze drying. The salt crystallised from acetone; m.p. indefinite - darkening and decomposing above 200"C.
Analysis:
Found C, 69.1; H, 6.2; N, 5.3; Caic for C23H16O11.(C9H22N2)2.1-21H2O C, 69.1; H, 6.1; N, 5.3;
EXAMPLE 3
Triprolidine Hydrochloride BP 1.0 g
Disodium Cromoglycate BP 20.0 g
Benzalkonium Chloride Solution USP (50% w/v) 0.31 ml
Disodium edetate 0.2 g
Distilled water to 1000 ml 1g of triprolidine hydrochloride was dissolved in 500 ml of an aqueous solution containing 20g of disodium cromoglycate and 0.2g of disodium edetate. The benzalkonium chloride was dissolved in a further 300 ml of water and this solution was added to the disodium cromoglycate solution. The bulk solution was made up to 1,000 ml with further water and sterile filtered. The composition was filled into 15 ml coloured bottles fitted with a device to administer metered doses of the liquid in spray form.
EXAMPLE 4
The composition of Example 3 was compared in blind crossover trials with a 2% aqueous solution of disodium cromoglycate and a placebo in 16 humans suffering from allergic rhinitis. The patients kept diary cards on which they expressed preferences for the compositions used. Analysis of the preferences showed a higher preference for the composition of Example 3 as compared to the 2% aqueous solution of disodium cromoglycate, and a highly significant preference for the composition of Example 3 as compared to placebo.
EXAMPLE 5
Triprolidine Hydrochloride B.P. 1.0g
Disodium Cromoglycate B.P. 20 0g Disodium Edetate B.P. 0.2 g
Benzoalkonium Chloride Solution USP, 50% w/r 0.4 ml
Phenylethyl Alcohol BPC (1963) 4.2 g
Distilled Water to 1000.0 ml
The Benzoalkonium Chloride Solution was dissolved with stirring in 300 ml of distilled water, and the Phenylethyl Alcohol was then added and dissolved with stirring. The
Disodium Edetate and Troprolidine Hydrochloride were dissolved in a further 500 ml of distilled water, and then the Disodium Cromoglycate added and dissolved. The two solutions were mixed together and made up to volume with distilled water. This final solution was sterile filtered and aseptically filled into 10 ml sterile polythene dropper bottles.
WHAT WE CLAIM IS:
1. A salt of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol with a basic compound
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (21)
1. A salt of 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol with a basic compound
which has an anti-histamine H1 receptor antagonist properties, and which contains a 6 membered nitrogen heterocyclic ring.
2. A salt according to Claim 1, wherein the anti-histamine is trimeprazine, cyproheptadine, pheniramine, mepyramine, chlorpheniramine, brompheniramine, dimethindene, carbinoxamine, tripelennamine or triprolidine.
3. A salt according to Claim 1 or Claim 2, which is at least 1% w/v soluble in water.
4. A salt according to Claim 3, which is at least 4% w/v soluble in water.
5. A process for the production of a salt according to Claim 1, which comprises reacting a suitable salt of 1,3-bis(2-carboxy-chromon-5-yloxy)propan-2-ol with an appropriate salt of the antihistamine, or by reacting l,3-bis(2-carboxychromon-5-yloxy)propan-2-ol with the free antihistamine base.
6. A pharmaceutical mixture comprising (a) one or more of l,3-bis(2-carboxychromon-5-yloxy)propan-2-ol, or a pharmaceutically acceptable salt thereof, as active ingredient in combination with (b) one or more anti-histamines having H1 receptor antagonist properties and which contains a 6 membered nitrogen heterocyclic ring.
7. A mixture according to Claim 6, which comprises disodium cromoglycate.
8. A mixture according to Claim 6 or 7, wherein the anti-histamine is trimeprazine, cyproheptadine, pheniramine, mepyramine, chlorpheniramine, brompheniramine, dimethindene, carbinoxamine, tripelennamine, triprolidine or a pharmaceutically acceptable salt thereof.
9. A mixture according to any one of Claims 6 to 8 containing only one active ingredient and only one antihistamine.
10. A mixture according to any one of Claims 6 to 9 containing from 1,000 to 0.2 parts by weight of active ingredient (measured as disodium cromoglycate) for each part by weight of anti-histamine.
11. A mixture according to Claim 10 containing from 40 to 0.5 parts by weight of active ingredient.
12. A mixture according to Claim 11 containing disodium cromoglycate and triprolidine in a weight ratio of 20:1.
13. A composition comprising a salt according to any one of Claims 1 to 4 or a mixture according to any one of Claims 6 to 12 in combination with an organic or inorganic pharmaceutically acceptable adjuvant or excipient.
14. A composition according to Claim 13 comprising an aqueous solution containing up to 10% by weight of the salt or mixture.
15. A composition according to Claim 13 or 14 containing a preservative, a sequestering agent or a buffer.
16. A composition according to Claim 15, wherein the preservative comprises benzalkonium chloride or phenyl ethyl alcohol.
17. A composition according to Claim 13 in powder form and comprising fine particles of the anithistamine and/or of the salt of 1,3-bis(2-carboxychromon-5-yloxy)-propam-2-ol.
18. Chlorpheniramine salt of 1 ,3-bis(2-carboxychromon-5-yloxy)-propan-2-ol.
19. Triprolidine salt of 1 ,3-bis(2-carboxychromon-5-yloxy)propan-2-ol.
20. A mixture according to Claim 6 and substantially as hereinbefore described in
Example 3.
21. A pharmaceutical package comprising at least one dose of 1,3-bis(2carboxychromon-5-yloxy)propan-2-ol, or a pharmaceutically acceptable salt thereof, and at least one dose of an antihistamine having H, receptor antagonist properties and which contains a 6 membered nitrogen heterocyclic ring, and wherein the doses are unit doses and are arranged in the package in a particular order together with written or printed indications or directions, the indications or directions and the manner of packing being such as to provide guidance in relation to, and to facilitate the taking of, a dose of active ingredient and a dose of the antihistamine in a particular order.
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB11390/77A GB1582362A (en) | 1977-03-17 | 1977-03-17 | Cromoglycic acid salts and compositions |
IL54264A IL54264A (en) | 1977-03-17 | 1978-03-13 | Pharmaceutical compositions comprising 1,3-bis(2-carboxychromon-5-yloxy)propan-2-ol and h1 anti-histamines |
BE185891A BE864837A (en) | 1977-03-17 | 1978-03-13 | ANTIALLERGIC COMPOSITION |
FI780782A FI780782A (en) | 1977-03-17 | 1978-03-13 | Komposition |
DK113378A DK113378A (en) | 1977-03-17 | 1978-03-14 | PROCEDURE FOR PREPARING SALTS OF 1,3-BIS (2-CARXYCHROMON-5-YLOXY) PROPAN-2-OL. |
DE19782810974 DE2810974A1 (en) | 1977-03-17 | 1978-03-14 | A SALT OF 1,3-BIS- (2-CARBOXYCHROMON-5-YLOXY) -PROPAN-2-OL AND ITS USE |
IE530/78A IE46581B1 (en) | 1977-03-17 | 1978-03-15 | Cromoglycic acid salts and compositions |
ZA00781520A ZA781520B (en) | 1977-03-17 | 1978-03-15 | Anti-histamine salts and mixtures |
NZ186712A NZ186712A (en) | 1977-03-17 | 1978-03-16 | Salts of 1,3-bis-(2-carboxychromon-5-yloxyd-propan-2-ol with basic antihistamine compounds mixtures of salts of 1,3-(2-carboxychromon-5-yloxy)propan-2-ol and basic antihistamine compounds |
CA299,237A CA1113862A (en) | 1977-03-17 | 1978-03-16 | Mixtures of 1,3-bis(2-carboxy-chromon-5-yloxy) propan- 2-ol or a salt thereof with an antihistamine having h.sub.1 receptor antagonist properties |
NO780935A NO152297C (en) | 1977-03-17 | 1978-03-16 | ANALOGY PROCEDURE FOR PREPARING A THERAPEUTIC ACTIVE SALT OF 1,3-BIS (2-CARBOXYCHROMON-5-YLOXY) -PROPAN-2-OL WITH AN ANTIHISTAMINE |
SE7803069A SE444939B (en) | 1977-03-17 | 1978-03-16 | PROCEDURE FOR PREPARING AN ANTIALLERGIC EFFECTIVE MIXTURE OF 1,3-BIS (2-CARBOXICROMON-5-YLOXY) PROPAN-2-OL AND ANTIHISTAMINE |
IT2128378A IT1158667B (en) | 1977-03-17 | 1978-03-16 | Bis-carboxy:chromonyl:oxy propanol salts with heterocyclic bases - used for treating and preventing eye, nose and skin allergies |
FR7807669A FR2383937A1 (en) | 1977-03-17 | 1978-03-16 | ANTIALLERGIC COMPOSITION CONTAINING AT LEAST ONE SALT OF 1,3-BIS (2-CARBOXYCHROMONE-5-YLOXY) PROPANE-2-OL |
CH289578A CH628517A5 (en) | 1977-03-17 | 1978-03-16 | Anti-allergic medicament |
NL7802869A NL7802869A (en) | 1977-03-17 | 1978-03-16 | ANTI-HISTAMINE SUBSTANCES AND PREPARATIONS INCLUDING THEM. |
LU79253A LU79253A1 (en) | 1977-03-17 | 1978-03-16 | ANTIALLERGIC COMPOSITION AND METHOD OF PREPARATION |
JP3002278A JPS53115823A (en) | 1977-03-17 | 1978-03-17 | Salt of chromon derivative and antiihistamine agent and mixture |
AU34272/78A AU516337B2 (en) | 1977-03-17 | 1978-03-17 | Salts of 1, 3-bis(2-carboxychromon-5-yloxy)propan-2-ol |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB11390/77A GB1582362A (en) | 1977-03-17 | 1977-03-17 | Cromoglycic acid salts and compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1582362A true GB1582362A (en) | 1981-01-07 |
Family
ID=9985349
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB11390/77A Expired GB1582362A (en) | 1977-03-17 | 1977-03-17 | Cromoglycic acid salts and compositions |
Country Status (18)
Country | Link |
---|---|
JP (1) | JPS53115823A (en) |
AU (1) | AU516337B2 (en) |
BE (1) | BE864837A (en) |
CA (1) | CA1113862A (en) |
CH (1) | CH628517A5 (en) |
DE (1) | DE2810974A1 (en) |
DK (1) | DK113378A (en) |
FI (1) | FI780782A (en) |
FR (1) | FR2383937A1 (en) |
GB (1) | GB1582362A (en) |
IE (1) | IE46581B1 (en) |
IL (1) | IL54264A (en) |
LU (1) | LU79253A1 (en) |
NL (1) | NL7802869A (en) |
NO (1) | NO152297C (en) |
NZ (1) | NZ186712A (en) |
SE (1) | SE444939B (en) |
ZA (1) | ZA781520B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0040489A1 (en) * | 1980-05-17 | 1981-11-25 | FISONS plc | Mixtures, salts, packages and pharmaceutical compositions containing 5-(2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid or a derivative thereof and an H2 receptor antagonist antihistamine |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA812811B (en) * | 1980-04-30 | 1982-06-30 | Fisons Ltd | Mixtures and salts of beta-2 selective bronchodilators with cromoglycic acid and salts thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL44022A0 (en) * | 1973-01-23 | 1974-05-16 | Fisons Ltd | Novel salts of anti-inflammatory quinoline derivatives,their preparation and pharmaceutical compositions containing them |
FR2217004A1 (en) * | 1973-02-15 | 1974-09-06 | Aries Robert | Sedatives and bronchodilatories - i.e. salts of 1,3-bis(2-carboxychromon-5-yloxy)propanes with 3-hydroxy-2-hydroxymethyl pyridines |
FR2230358A2 (en) * | 1973-05-25 | 1974-12-20 | Fisons Ltd | Cromoglycate contg. solns. - contg. a second therapeutically active cpd. e.g. an antihistamine |
DE2535258C2 (en) * | 1974-08-10 | 1993-06-03 | Fisons Plc, Ipswich, Suffolk | Inhalable drug in pellet form |
-
1977
- 1977-03-17 GB GB11390/77A patent/GB1582362A/en not_active Expired
-
1978
- 1978-03-13 FI FI780782A patent/FI780782A/en not_active Application Discontinuation
- 1978-03-13 BE BE185891A patent/BE864837A/en not_active IP Right Cessation
- 1978-03-13 IL IL54264A patent/IL54264A/en unknown
- 1978-03-14 DE DE19782810974 patent/DE2810974A1/en active Granted
- 1978-03-14 DK DK113378A patent/DK113378A/en not_active Application Discontinuation
- 1978-03-15 IE IE530/78A patent/IE46581B1/en not_active IP Right Cessation
- 1978-03-15 ZA ZA00781520A patent/ZA781520B/en unknown
- 1978-03-16 CH CH289578A patent/CH628517A5/en not_active IP Right Cessation
- 1978-03-16 NL NL7802869A patent/NL7802869A/en not_active Application Discontinuation
- 1978-03-16 NZ NZ186712A patent/NZ186712A/en unknown
- 1978-03-16 FR FR7807669A patent/FR2383937A1/en active Granted
- 1978-03-16 NO NO780935A patent/NO152297C/en unknown
- 1978-03-16 CA CA299,237A patent/CA1113862A/en not_active Expired
- 1978-03-16 LU LU79253A patent/LU79253A1/en unknown
- 1978-03-16 SE SE7803069A patent/SE444939B/en not_active IP Right Cessation
- 1978-03-17 JP JP3002278A patent/JPS53115823A/en active Pending
- 1978-03-17 AU AU34272/78A patent/AU516337B2/en not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0040489A1 (en) * | 1980-05-17 | 1981-11-25 | FISONS plc | Mixtures, salts, packages and pharmaceutical compositions containing 5-(2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid or a derivative thereof and an H2 receptor antagonist antihistamine |
Also Published As
Publication number | Publication date |
---|---|
BE864837A (en) | 1978-09-13 |
FR2383937A1 (en) | 1978-10-13 |
ZA781520B (en) | 1979-04-25 |
IE780530L (en) | 1978-09-17 |
FI780782A (en) | 1978-09-18 |
AU516337B2 (en) | 1981-05-28 |
IL54264A0 (en) | 1978-06-15 |
AU3427278A (en) | 1979-09-20 |
IE46581B1 (en) | 1983-07-27 |
DK113378A (en) | 1978-09-18 |
SE444939B (en) | 1986-05-20 |
CA1113862A (en) | 1981-12-08 |
FR2383937B1 (en) | 1982-07-23 |
NZ186712A (en) | 1979-12-11 |
LU79253A1 (en) | 1978-10-17 |
IL54264A (en) | 1984-01-31 |
CH628517A5 (en) | 1982-03-15 |
NO152297B (en) | 1985-05-28 |
NL7802869A (en) | 1978-09-19 |
SE7803069L (en) | 1978-09-18 |
NO780935L (en) | 1978-09-19 |
DE2810974C2 (en) | 1988-07-21 |
JPS53115823A (en) | 1978-10-09 |
DE2810974A1 (en) | 1978-09-21 |
NO152297C (en) | 1985-09-04 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed [section 19, patents act 1949] | ||
704A | Declaration that licence is not available as of right for an excepted use (par. 4a/1977) | ||
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19970303 |