NO871058L - PROCEDURE AND PREPARATION FOR TREATMENT OF BRONCHOSPASTIC RESPIRATORY DISEASES. - Google Patents
PROCEDURE AND PREPARATION FOR TREATMENT OF BRONCHOSPASTIC RESPIRATORY DISEASES. Download PDFInfo
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- NO871058L NO871058L NO871058A NO871058A NO871058L NO 871058 L NO871058 L NO 871058L NO 871058 A NO871058 A NO 871058A NO 871058 A NO871058 A NO 871058A NO 871058 L NO871058 L NO 871058L
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- Prior art keywords
- gallopamil
- preparation
- administered
- treatment
- bronchospastic
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 14
- 238000000034 method Methods 0.000 title claims description 9
- 239000004044 bronchoconstricting agent Substances 0.000 title claims description 8
- 230000002741 bronchospastic effect Effects 0.000 title claims description 8
- 201000010099 disease Diseases 0.000 title claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 5
- 230000000241 respiratory effect Effects 0.000 title description 2
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 claims description 28
- 229960000457 gallopamil Drugs 0.000 claims description 28
- 230000036428 airway hyperreactivity Effects 0.000 claims description 14
- 239000000443 aerosol Substances 0.000 claims description 7
- 229940071648 metered dose inhaler Drugs 0.000 claims description 4
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 229940127291 Calcium channel antagonist Drugs 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000000480 calcium channel blocker Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
- 208000009079 Bronchial Spasm Diseases 0.000 description 3
- 208000014181 Bronchial disease Diseases 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 229960001722 verapamil Drugs 0.000 description 3
- 239000013566 allergen Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960001597 nifedipine Drugs 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 206010003557 Asthma exercise induced Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- -1 exercise Substances 0.000 description 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000029219 regulation of pH Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
Description
Fremgangsmåte og preparat for behandling av bronkospastiske luftveisykdommer Method and preparation for the treatment of bronchospastic respiratory diseases
BAKGRUNN FOR OPPFINNELSENBACKGROUND OF THE INVENTION
1. OppfinneIsesområde1. Invent Ice area
Foreliggende oppfinnelse er rettet mot behandlingenThe present invention is directed towards the treatment
av bronkospastiske luftveisykdommer, særlig reversibel luftveihyperreaktivitet, med en kalsiumsporblokker. Nærmere bestemt vedrører oppfinnelsen slik behandling ved anvendelse av kalsiumsporblokkeren Gallopamil. of bronchospastic airway diseases, particularly reversible airway hyperreactivity, with a calcium channel blocker. More specifically, the invention relates to such treatment using the calcium channel blocker Gallopamil.
2. Beskrivelse av teknikkens stand2. Description of the state of the art
Forbindelsen Gallopamil er en kjent kalsiumsporblokker. The compound Gallopamil is a known calcium channel blocker.
På samme måte som andre kalsiumsporblokkere, slik som Nifedipine, Diltiazim og Verapamil, brukes Gallopamil i kardiovaskulær terapi. Verapamil, Diltiazim og Nifedipine er blitt testet med hensyn på mulig bruk som aktive terapeutiske midler i behandling av reversibel luftveihyperreaktivitet. De doseringer som har vært nødvendige for å oppnå den ønskede reduksjon av luftveihyperreaktivitet, har imidlertid resultert i uønskede bivirkninger, slik som bronkospasme. Dessuten har doseringene vært like høye som eller høyere enn doseringene brukt i kardiovaskulær terapi. In the same way as other calcium channel blockers, such as Nifedipine, Diltiazim and Verapamil, Gallopamil is used in cardiovascular therapy. Verapamil, Diltiazim and Nifedipine have been tested for possible use as active therapeutic agents in the treatment of reversible airway hyperreactivity. However, the dosages that have been necessary to achieve the desired reduction of airway hyperreactivity have resulted in unwanted side effects, such as bronchospasm. Moreover, the dosages have been as high as or higher than the dosages used in cardiovascular therapy.
OPPSUMMERING AV OPPFINNELSENSUMMARY OF THE INVENTION
I et første aspekt er foreliggende oppfinnelse rettet mot en fremgangsmåte for behandling av bronkospastisk sykdom kjennetegnet ved luftveihyperreaktivitet som omfatter administrering til et individ av en Gallopamilmengde som er til-strekkelig til å redusere luftveihyperreaktivitet, særlig via en pulmonar vei. In a first aspect, the present invention is directed to a method for treating bronchospastic disease characterized by airway hyperreactivity which comprises administering to an individual an amount of Gallopamil which is sufficient to reduce airway hyperreactivity, particularly via a pulmonary route.
Et annet aspekt ved oppfinnelsen omfatter et preparat for behandling av en bronkospastisk sykdom kjennetegnet ved luftveihyperreaktivitet, som omfatter en Gallopamilmengde som effektivt virker til å redusere luftveihyperreaktivitet, og en farmasøytisk akseptabel bærer, hjelpestoff eller tilset-ningsstoff, særlig i en form som er egnet for aerosoladministrering. Another aspect of the invention comprises a preparation for the treatment of a bronchospastic disease characterized by airway hyperreactivity, which comprises an amount of Gallopamil which effectively acts to reduce airway hyperreactivity, and a pharmaceutically acceptable carrier, excipient or additive, particularly in a form suitable for aerosol administration.
NÆRMERE BESKRIVELSE AV OPPFINNELSENDETAILED DESCRIPTION OF THE INVENTION
Foreliggende oppfinnelse vedrører behandling av bronkospastiske luftveisykdommer, særlig reversibel luftveihyper reaktivitet, ved administrering av kalsiumsporblokkeren Gallopamil (5-[[2-(3,4-dimethoxyfenyl)ethyl]methylamino]-2-isopropy1-2-[3,4,5-trimethoxyfenyl]pentanonitril-hydroklorid). Uttrykket "Gallopamil" er ment å dekke anvendbare derivater, slik som andre farmasøytiske akseptable salter, ikke-salt-former, etc. Uttrykket "reversibel luftveihyperreaktivitet" henviser til slike tilstander som allergen- og mosjonsindusert astma etc, som resulterer i reversibel blokkering av luft-passasjene. Såkalte irreversible luftveitilstander, slik som emfysem, omfatter også reversible aspekter. Det er forventet at foreliggende oppfinnelse vil være mest anvendbar i behandling av kroniske tilstander. The present invention relates to the treatment of bronchospastic airway diseases, in particular reversible airway hyper reactivity, by administering the calcium channel blocker Gallopamil (5-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]-2-isopropyl1-2-[3,4,5- trimethoxyphenyl]pentanonitrile hydrochloride). The term "Gallopamil" is intended to cover applicable derivatives, such as other pharmaceutically acceptable salts, non-salt forms, etc. The term "reversible airway hyperreactivity" refers to such conditions as allergen and exercise-induced asthma etc, which result in reversible blockage of air - the passages. So-called irreversible respiratory conditions, such as emphysema, also include reversible aspects. It is expected that the present invention will be most applicable in the treatment of chronic conditions.
Det er foretrukket at Gallopamil administreres på en pulmonar måte, dvs. direkte til lungene i form av en aerosol. Slik aerosoladministrering kan være i form av en forstøvet saltoppløsning. Generelt kan oppløsningen omfatte ca. en halv - 1 vekt% Gallopamil i 0,4% saltoppløsning. Oppløselighet av Gallopamil i oppløsningen forbedres ved tilsetning av opp-løseliggjørere, slik som ethanol og propylenglycol, begge i mengder på f.eks. 4 vekt%. Regulering av pH bør utføres med natriumbicarbonat. Alternativt kan Gallopamil dispergeres i freon og administreres gjennom en inhalator med utmålt dose. Det er særlig ønskelig å bruke en inhalator med utmålt dose It is preferred that Gallopamil is administered in a pulmonary way, i.e. directly to the lungs in the form of an aerosol. Such aerosol administration may be in the form of a nebulized saline solution. In general, the solution can include approx. half - 1% by weight Gallopamil in 0.4% saline solution. Solubility of Gallopamil in the solution is improved by the addition of solubilizers, such as ethanol and propylene glycol, both in amounts of e.g. 4% by weight. Regulation of pH should be carried out with sodium bicarbonate. Alternatively, Gallopamil can be dispersed in freon and administered through a metered-dose inhaler. It is particularly desirable to use an inhaler with a measured dose
og med en slik innåndingsanordning som den som er beskrevet i US patentskrift nr. 4 484 577. and with such an inhalation device as that described in US Patent No. 4,484,577.
Oral administrering i form av tabletter eller kapsler er mulig, men kan være ufordelaktig ettersom det er påkrevet med høyere doseringer, noe som muligens fører til uønskede kardiovaskulære virkninger. Parenteral og topisk administrering er også mulig, selv om de ikke er foretrukket på grunn av ubekvemhet og større påkrevet dosering. Parenteral administrering ville likeledes være mest anvendbar i nødssituasjoner, men det menes at foreliggende oppfinnelse vil være mest anvendbar på en preventiv måte eller for lindring via selv-administrering. Oral administration in the form of tablets or capsules is possible, but may be disadvantageous as higher dosages are required, possibly leading to adverse cardiovascular effects. Parenteral and topical administration are also possible, although they are not preferred due to inconvenience and larger dosage required. Parenteral administration would likewise be most applicable in emergency situations, but it is believed that the present invention will be most applicable in a preventive manner or for relief via self-administration.
Når Gallopamil avleveres via en forstøvet saltoppløs-ning, bør det brukes nok oppløsning til å gi en Gallopamildose på ca. 1-20 mg, fortrinnsvis 1-10 mg. Denne dosering kan gjentas opp til tre eller fire ganger pr. dag. Når en inhalator med utmålt dose brukes i stedet for forstøvningen, kan Gallopamildosen reduseres til ca. en tiendedel av den for-støvede dose, fortrinnsvis ca. 0,1 - 1 mg Gallopamil. When Gallopamil is delivered via a nebulized saline solution, enough solution should be used to give a Gallopamil dose of approx. 1-20 mg, preferably 1-10 mg. This dosage can be repeated up to three or four times per day. When a metered-dose inhaler is used instead of nebulisation, the Gallopamil dose can be reduced to approx. one tenth of the dusted dose, preferably approx. 0.1 - 1 mg Gallopamil.
Som angitt ovenfor, kan et forstøvet aerosolpreparat lages ved å bruke 0,4% saltoppløsning som bærer for Gallopamil som skal avleveres på en forstøvet måte. Egnede oppløse-liggjørere og andre for tiden kjente bestanddeler for aerosol-preparater kan brukes dersom det er nødvendig eller ønsket. Bærergasser som for tiden er blitt kjente for bruk i inhala-torer med utmålt dose, slik som freon, er egnet for administrering av Gallopamil fra en inhalator med utmålt dose. As indicated above, a nebulized aerosol preparation can be made using 0.4% saline as a carrier for Gallopamil to be delivered in a nebulized manner. Suitable solubilizers and other currently known ingredients for aerosol preparations can be used if necessary or desired. Carrier gases currently known for use in metered dose inhalers, such as freon, are suitable for administration of Gallopamil from a metered dose inhaler.
EksempelExample
Individer som var påvist å være mottagelige for periodisk tilbakevendende astmaangrep på grunn av slike år-saker som allergener, mosjon, røyk etc, ble valgt ut. Dosen (PD2q) av methacholin (et induksjonsmiddel for astma) som er nødvendig for å gi en 20% reduksjon i "forced expired volume" i løpet av et sekund (FEV^), ble bestemt for hvert individ, Individuals who had been shown to be susceptible to periodically recurring asthma attacks due to such year-things as allergens, exercise, smoke, etc., were selected. The dose (PD2q) of methacholine (an asthma inducer) required to produce a 20% reduction in forced expired volume in one second (FEV^) was determined for each subject,
og hvert individ hadde en PD20SOm var m:"-nc^re enn ^ mg/ml. Administrering av forstøvet Gallopamil (3 ml av en oppløsning som inneholdt Gallopamilmengder varierende fra 1 til 20 mg, and each subject had a PD20SOm greater than 1 mg/ml. Administration of nebulized Gallopamil (3 ml of a solution containing Gallopamil amounts varying from 1 to 20 mg,
4% ethanol og 4% propylenglycol i steril saltoppløsning, pH regulert til 6 med natriumbicarbonat) økte PD2o^or metnacnol;'-n med 2 -3 ganger, og ga følgelig betydelig reduksjon i luftveihyperreaktivitet. Det var ingen kardiovaskulær aktivitet av betydning og uønskede bivirkninger, slik som bronkospasmer, var ikke tilstede. Omtrent 10 ganger så mye Verapamil ga ikke en så stor PD2Q-økning, og større doseringer resulterte i bronkospasme. 4% ethanol and 4% propylene glycol in sterile saline, pH adjusted to 6 with sodium bicarbonate) increased the PD2o^or metnacnol;'-n by 2-3 times, and consequently produced a significant reduction in airway hyperreactivity. There was no significant cardiovascular activity and unwanted side effects, such as bronchospasm, were not present. Approximately 10 times as much Verapamil did not produce as large a PD2Q increase, and larger doses resulted in bronchospasm.
Claims (12)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75469485A | 1985-07-15 | 1985-07-15 | |
| US06/790,408 US4689213A (en) | 1985-07-15 | 1985-10-23 | Method and composition for treating bronchospastic airway diseases |
| PCT/US1986/001443 WO1987000431A1 (en) | 1985-07-15 | 1986-07-14 | Use of gallopamil for treating bronchospastic airway diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO871058D0 NO871058D0 (en) | 1987-03-13 |
| NO871058L true NO871058L (en) | 1987-03-13 |
Family
ID=27375246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO871058A NO871058L (en) | 1985-07-15 | 1987-03-13 | PROCEDURE AND PREPARATION FOR TREATMENT OF BRONCHOSPASTIC RESPIRATORY DISEASES. |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO871058L (en) |
-
1987
- 1987-03-13 NO NO871058A patent/NO871058L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO871058D0 (en) | 1987-03-13 |
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