CA1131131A - Preparation for the treatment of nasal hypersecretion - Google Patents
Preparation for the treatment of nasal hypersecretionInfo
- Publication number
- CA1131131A CA1131131A CA321,974A CA321974A CA1131131A CA 1131131 A CA1131131 A CA 1131131A CA 321974 A CA321974 A CA 321974A CA 1131131 A CA1131131 A CA 1131131A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- pharmaceutically acceptable
- carrier
- acceptable diluent
- methobromide
- 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.)
- Expired
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The invention is a pharmaceutical composition for topical applica-tion to the nose to combat nasal hypersecretion, which comprises a quater-nary tropane alkaloid derivative with atropine-like activity, i.e. vagus blocking activity, and a pharmaceutically acceptable carrier or diluent.
The preferred quaternary tropane alkaloid derivative is N-isopropyl nortro-pine tropic acid ester methobromide.
The invention is a pharmaceutical composition for topical applica-tion to the nose to combat nasal hypersecretion, which comprises a quater-nary tropane alkaloid derivative with atropine-like activity, i.e. vagus blocking activity, and a pharmaceutically acceptable carrier or diluent.
The preferred quaternary tropane alkaloid derivative is N-isopropyl nortro-pine tropic acid ester methobromide.
Description
113~3~
The invention relates tonovel compositions for the treatment of nasal hypersecretion ("runny nose").
For the treatment of this disease various groups of active sub-stances are presently used, but none is completely satisfactory. For example, it is known to use vasoconstrictors with aminoethanol or imidazoline structure, but side-effects such as marked dryness-of-the-mouth as well as possibly also sedative effects such as the so-called rebound-phenomenon have to be accepted. Furthermore, disodium cromoglycate (DNCG) or corticosteroids such as beclamethasone dipropionate are in use. However, these active sub-stances mainly relieve the symptoms of the allergenic variants of perennialrhinitis, for instance hay fever; moreover, in connection with the use of corticosteroids (especially in the case of long-term medication) the special risks of this class of substances (occurrence of mycoses, negative effect on the mineral balance and blood sugar level, mucous membrane atrophy) have to be taken into account.
The object of this invention is, therefore, to provide compositions which make possible a practically side-effect-free therapy of all manifest forms of nasal hypersecretion.
The present invention provides a composition for topical applica-tion to the nose for treatment of nasal hypersecretion which contains aquaternary tropane alkaloid derivative with atropine-like activity and a pharmaceutically acceptable diluent or carrier.
Thus, the invention provides a composition for topical administra-tion of those quaternary tropane alkaloid derivatives which exhibit an atropine-like, i.e. vagus-blocking, activity in the area of the nasal mucous membrane. The compositions according to the present invention, therefore, are pharmaceutical preparations of tropane alkaloid derivatives suitable for topical administration to the nasal mucous membrane with a specific vagus-113113i.
blocking effect at the point of application.
Active ingredients suitable for these compositions are, for exam-ple, the following substances:
N-Isopropyl nortropine tropic acid ester methobromide, N-Ethyl-norscopolamine methobromide, N-Methyl-scopolarnmonium bromide, N-Ethyl-scopolammonium bromide, N-Ethyl-o-benzoyl-narscopolamine methobrornide N-Norscopolamine ethobromide.
Formulations of the active substances suitable for topical applica-tion to the nasal mucous membrane are, for example, aqueous solutions (applic-able by way of an eye-dropper) or - preferably - aerosols, where those operated by means of propellant gases or also propellant gas-free aerosols, such as the so-called metering pump aerosols, may be used. The latter are preferred because of their low irritating effect on the nasal mucous mem-brane.
The novel compositions according to the invention provide for the first time the possibility of rapidly and surely bringing, for example, also non-allergenic forms of perennial rhinitis under control without the occur-rence of undesirable side-effects. They further make it possible to combat nasal hypersecretion already in the initial stage. Particularly advantageous for this purpose have proved to be those compositions which contain the active substance N-isopropylnortropine tropic acid ester methobromide (ipratopium bromide). In one aspect of the invention, a suitable daily dose is from 80 to 320 mcg, preferably 120 to 180 mcg. In another aspect, the daily dose amounts to between 150-500 mcg, preferably 200-350 mc. In the case of ametering aerosol which delivers, for example, 20 mcg per actuation, two or possibly also three actuations, single dose 80-120 mcg, are sprayed three to four times daily into each nostril, so that a daily dose between 240 and 480 mcg is achieved.
It is also possible to combine the effective tropane alkaloids according to the invention with other substances which are active in the nose, such as beclamethasone dipropionate or fenoterol. Especially the com-bination with fenoterol exhibits very favorable effects, because it is thereby possible also to include allergenic forms of rhinitis. In this com-bination the daily dose of fenoterol can be 4-5 times higher than the daily dose of ipratropium bromide, which is due to the different activity of the two substances.
The following examples illustrate the invention without limiting it:
a) Metering pump aerosol Ipratropium bromide 3.33 mg Surfactive substance, for instance benzalkonium chloride 5.00 mg lN HCl (for adjustment of the pH to 3.4) 0.018 ml Demineralized water ad 20 ml This solution is filled into a bottle provided with a metering pump aerosol device which is additionally equipped with a nose adapter. The pump of the aerosol is adjusted so that it expels 60 ml per stroke.
In place of 3.33 mg active substance, an amount of 16.67 mg active substance may also be used. In this manner an aerosol liquid with a higher dose is obtained for the purpose of combating stubborn cases.
b) Metered-dose aerosol with propellant gas.
1 dose contains:
~13~13,~1L
Ipratopiurn bromide 0.02 mg Surf'active substance, for instance sorbitan trioleate 0.03-0.3 mg Propellant gas mixture of mono-fluoro-trichloromethane, difluoro-dichloromethane and tetra-fluoro-dichloromethane ad 70 mg The above mixture (in an amount which corresponds to about 200 doses) is filled into pressurized gas containers which are equipped with a conventional metering valve and nose adapter.
c) Nose drops Ipratropium bromide 0.25 mg Fenoterol 1.00 mg Demineralized water ad 10 ml The above-described solution is filled into small brown bottles which are closed with a threaded cap (which comprises a built-in nose drop-per). The doses of the active substances are such that, by means of 2 to 3 drops (0.1 to 0.15 ml), the suitable single dose of the tropane alkaloid (about 20 to 25 mcg for each nostril) can be applied to the nasal mucous membrane.
The invention relates tonovel compositions for the treatment of nasal hypersecretion ("runny nose").
For the treatment of this disease various groups of active sub-stances are presently used, but none is completely satisfactory. For example, it is known to use vasoconstrictors with aminoethanol or imidazoline structure, but side-effects such as marked dryness-of-the-mouth as well as possibly also sedative effects such as the so-called rebound-phenomenon have to be accepted. Furthermore, disodium cromoglycate (DNCG) or corticosteroids such as beclamethasone dipropionate are in use. However, these active sub-stances mainly relieve the symptoms of the allergenic variants of perennialrhinitis, for instance hay fever; moreover, in connection with the use of corticosteroids (especially in the case of long-term medication) the special risks of this class of substances (occurrence of mycoses, negative effect on the mineral balance and blood sugar level, mucous membrane atrophy) have to be taken into account.
The object of this invention is, therefore, to provide compositions which make possible a practically side-effect-free therapy of all manifest forms of nasal hypersecretion.
The present invention provides a composition for topical applica-tion to the nose for treatment of nasal hypersecretion which contains aquaternary tropane alkaloid derivative with atropine-like activity and a pharmaceutically acceptable diluent or carrier.
Thus, the invention provides a composition for topical administra-tion of those quaternary tropane alkaloid derivatives which exhibit an atropine-like, i.e. vagus-blocking, activity in the area of the nasal mucous membrane. The compositions according to the present invention, therefore, are pharmaceutical preparations of tropane alkaloid derivatives suitable for topical administration to the nasal mucous membrane with a specific vagus-113113i.
blocking effect at the point of application.
Active ingredients suitable for these compositions are, for exam-ple, the following substances:
N-Isopropyl nortropine tropic acid ester methobromide, N-Ethyl-norscopolamine methobromide, N-Methyl-scopolarnmonium bromide, N-Ethyl-scopolammonium bromide, N-Ethyl-o-benzoyl-narscopolamine methobrornide N-Norscopolamine ethobromide.
Formulations of the active substances suitable for topical applica-tion to the nasal mucous membrane are, for example, aqueous solutions (applic-able by way of an eye-dropper) or - preferably - aerosols, where those operated by means of propellant gases or also propellant gas-free aerosols, such as the so-called metering pump aerosols, may be used. The latter are preferred because of their low irritating effect on the nasal mucous mem-brane.
The novel compositions according to the invention provide for the first time the possibility of rapidly and surely bringing, for example, also non-allergenic forms of perennial rhinitis under control without the occur-rence of undesirable side-effects. They further make it possible to combat nasal hypersecretion already in the initial stage. Particularly advantageous for this purpose have proved to be those compositions which contain the active substance N-isopropylnortropine tropic acid ester methobromide (ipratopium bromide). In one aspect of the invention, a suitable daily dose is from 80 to 320 mcg, preferably 120 to 180 mcg. In another aspect, the daily dose amounts to between 150-500 mcg, preferably 200-350 mc. In the case of ametering aerosol which delivers, for example, 20 mcg per actuation, two or possibly also three actuations, single dose 80-120 mcg, are sprayed three to four times daily into each nostril, so that a daily dose between 240 and 480 mcg is achieved.
It is also possible to combine the effective tropane alkaloids according to the invention with other substances which are active in the nose, such as beclamethasone dipropionate or fenoterol. Especially the com-bination with fenoterol exhibits very favorable effects, because it is thereby possible also to include allergenic forms of rhinitis. In this com-bination the daily dose of fenoterol can be 4-5 times higher than the daily dose of ipratropium bromide, which is due to the different activity of the two substances.
The following examples illustrate the invention without limiting it:
a) Metering pump aerosol Ipratropium bromide 3.33 mg Surfactive substance, for instance benzalkonium chloride 5.00 mg lN HCl (for adjustment of the pH to 3.4) 0.018 ml Demineralized water ad 20 ml This solution is filled into a bottle provided with a metering pump aerosol device which is additionally equipped with a nose adapter. The pump of the aerosol is adjusted so that it expels 60 ml per stroke.
In place of 3.33 mg active substance, an amount of 16.67 mg active substance may also be used. In this manner an aerosol liquid with a higher dose is obtained for the purpose of combating stubborn cases.
b) Metered-dose aerosol with propellant gas.
1 dose contains:
~13~13,~1L
Ipratopiurn bromide 0.02 mg Surf'active substance, for instance sorbitan trioleate 0.03-0.3 mg Propellant gas mixture of mono-fluoro-trichloromethane, difluoro-dichloromethane and tetra-fluoro-dichloromethane ad 70 mg The above mixture (in an amount which corresponds to about 200 doses) is filled into pressurized gas containers which are equipped with a conventional metering valve and nose adapter.
c) Nose drops Ipratropium bromide 0.25 mg Fenoterol 1.00 mg Demineralized water ad 10 ml The above-described solution is filled into small brown bottles which are closed with a threaded cap (which comprises a built-in nose drop-per). The doses of the active substances are such that, by means of 2 to 3 drops (0.1 to 0.15 ml), the suitable single dose of the tropane alkaloid (about 20 to 25 mcg for each nostril) can be applied to the nasal mucous membrane.
Claims (14)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A composition for topical application to the nose for treatment of nasal hypersecretion which contains a quaternary tropane alkaloid deriv-ative with atropine-like activity and a pharmaceutically acceptable diluent or carrier
2. A composition as claimed in claim 1 wherein the pharmaceutically acceptable diluent or carrier is demineralized water.
3. A composition as claimed in claim 1 wherein the pharmaceutically acceptable diluent or carrier is demineralized water containing a surface active active agent.
4. A composition as claimed in claim 1 wherein the pharmaceutically acceptable diluent or carrier is demineralized water containing a surface active agent which is benzalkonium chloride or sorbitan trioleate.
5. A composition as claimed in claim 2, 3 or 4 which is acidified with hydrochloric acid to a pH of about 3.6.
6. A composition as claimed in claim 2, 3 or 4 which also contains an additional nasally active substance.
7. A composition as claimed in claim 2, 3 or 4 which also contains fenoterol.
8. A composition as claimed in claim 2, 3 or 4 which also contains beclamethasone diproprionate.
9. A composition as claimed in claim 2, 3 or 4 which contains as the active ingredient N-isopropylnortropine tropic acid ester methobromide (ipratropium bromide).
10. A composition as claimed in claim 2, 3 or 4 which is in the form of an aqueous solution contained in a pipette bottle.
11. A composition as claimed in claim 2, 3 or 4 which is in the form of a propellant gas-free preparation suitable for atomizing as an aerosol.
12. A composition as claimed in claim l wherein the active ingre-dient is in the form of a suspension in a liquefied propellant gas mixture under pressure.
13. A composition as claimed in 2, 3 or 4 which contains ipratropium bromide and fenoterol in a pharmaceutical formulation suitable for topical application to the nose.
14. A composition as claimed in claim 2, 3 or 4 wherein the quaternary tropane alkaloid derivative is N-isopropyl nortropine tropic acid ester methobromide, N-ethyl norscopolamine methobromide, N-methyl scopolammonium bromide, N-ethyl scopolammonium bromide, N-ethyl-o-benzoyl-norscopolamine methobromide or N-norscopolamine ethobromide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA321,974A CA1131131A (en) | 1979-02-21 | 1979-02-21 | Preparation for the treatment of nasal hypersecretion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA321,974A CA1131131A (en) | 1979-02-21 | 1979-02-21 | Preparation for the treatment of nasal hypersecretion |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1131131A true CA1131131A (en) | 1982-09-07 |
Family
ID=4113592
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA321,974A Expired CA1131131A (en) | 1979-02-21 | 1979-02-21 | Preparation for the treatment of nasal hypersecretion |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1131131A (en) |
-
1979
- 1979-02-21 CA CA321,974A patent/CA1131131A/en not_active Expired
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |