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WO1993009778A2 - Utilisation de brl 38227 pour le traitement et la prophylaxie de l'hyperlipidemie - Google Patents

Utilisation de brl 38227 pour le traitement et la prophylaxie de l'hyperlipidemie Download PDF

Info

Publication number
WO1993009778A2
WO1993009778A2 PCT/GB1992/002141 GB9202141W WO9309778A2 WO 1993009778 A2 WO1993009778 A2 WO 1993009778A2 GB 9202141 W GB9202141 W GB 9202141W WO 9309778 A2 WO9309778 A2 WO 9309778A2
Authority
WO
WIPO (PCT)
Prior art keywords
hyperlipidemia
treatment
prophylaxis
brl
pharmaceutically acceptable
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.)
Ceased
Application number
PCT/GB1992/002141
Other languages
English (en)
Other versions
WO1993009778A3 (fr
Inventor
Thomas Conway Hamilton
Timothy Charles Gadsden Tasker
David Robert Howlett
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of WO1993009778A2 publication Critical patent/WO1993009778A2/fr
Publication of WO1993009778A3 publication Critical patent/WO1993009778A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil

Definitions

  • the present invention relates to a method for the treatment and/or prophylaxis of hyperlipidemia.
  • EP-A-120428 (Beecham Group p.l.c.) describes the potassium channel activator, BRL 38227 and its use as an antihypertensive agent.
  • BRL 38227 lowers the level of plasma lipids such as triglycerides and cholesterol. As such, this compound is of value in the treatment of hyperlipidemia, and is especially useful in the lowering of lipid levels in hypertensive patients. It is also known that certain classes of compound tend to be associated with increasing lipid levels in patients, such as ⁇ -blockers or diuretics, thus, BRL 38227 in combination with ⁇ -blockers and/or diuretics has the potential of counteracting the lipid raising effects of these agents.
  • the present invention provides a method for the treatment and/or prophylaxis of hyperlipidemia especially that associated with ⁇ - blockers or diuretic therapy in mammals, such as humans, especially those also suffering from hypertension (which is concomitantly treated), which method comprises administering to the mammal in need of such treatment and/or prophylaxis an effective and/or prophylactic amount of BRL 38227, or a pharmaceutically acceptable salt thereof.
  • BRL 38227 is suitable for specifically reducing the percentage of low density lipoproteins (LDL) in patients as well as the percentage of triglycerides and cholesterol which are the lipids associated with artery hardening. The reduction of such lipids is believed to be of benefit to the patient.
  • LDL low density lipoproteins
  • HDL high density lipoproteins
  • BRL 38227 is the (-)-enantiomer of the compound of Example 1 of EP-A- 76075 and United States Patent No. 4446113, ( ⁇ )-6-cyano-3,4-dihydro-2,2- dimethyl-trans-4-(2-oxo- 1- pyrrolidinyl)-2H-benzo[b]pyran-3-ol.
  • Examples of pharmaceutically acceptable salts are as described in the aforementioned European Patent references, the subject matter of which are incorporated herein by reference.
  • references to BRL 38227 include solvates such as hydrates.
  • BRL 38227 may be prepared as described in the aforementioned Patent Publications/References, or as described in EP-A-385584 (Beecham Group p.l. ⁇ ).
  • BRL 38227 is in substantially pure pharmaceutically acceptable form.
  • the administration of the compound may be by way of oral, sublingual, transdermal or parenteral administration.
  • a unit dose will normally contain 0.1 to 50 mgfor example 0.5 to 10 mg, of BRL 38227.
  • Unit doses will normally be administered once or more than once a day, for example 2, 3, or 4 times a day, more usually 1 to 3 times a day, such that the total daily dose is normally in the range, for a 70 kg adult of 0.1 to 50 mg, for example 0.5 to 10 mg, that is in the range of approximately 0.001 to 1 mg/kg/day, more usually 0.005 to 0.2 mg/kg/day.
  • BRL 38227 is administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
  • compositions are prepared by admixture and are suitably adapted for oral or parenteral aoministration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories.
  • Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
  • Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, d luents, tabletting agents, lubricants, disintegrants, colourants, 5 flavourings, and wetting agents.
  • the tablets may be coated according to well known methods in the art.
  • Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
  • Suitable disintegrants include starch, 10 polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate.
  • Suitable lubricants include, for example, magnesium stearate.
  • Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
  • compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional
  • additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated
  • coconut oil oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
  • fluid unit dose forms are prepared containing the potassium channel activator and a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform, distribution of the compound.
  • formulations suitable for topical use may be employed, optionally containing penetration enhancers.
  • compositions will usually be accompanied by written or printed directions for use in the treatment concerned.
  • the present invention also provides the use of BRL 38227, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment and/or prophylaxis of hyperlipidemia especially that associated with ⁇ -blockers or diuretic therapy .
  • Such treatment and/or prophylaxis may be carried out as hereinbefore described.
  • the above use of BRL 38227 is especially beneficial to patients also suffering from hypertension, (which is concomitantly treated).
  • the present invention further provides a pharmaceutical composition for use in the treatment and/or prophylaxis of hyperlipidemia especially that associated with ⁇ -blockers or diuretic therapy which comprises BRL 38227 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition for use in the treatment and/or prophylaxis of hyperlipidemia especially that associated with ⁇ -blockers or diuretic therapy which comprises BRL 38227 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
  • the above pharmaceutical composition is especially beneficial to patients also suffering from hypertension, (which is concomitantly treated).
  • compositions may be prepared in the manner as hereinbefore described.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Procédé de traitement et/ou de prophylaxie de l'hyperlipidémie chez les mammifières, dans lequel on administre au mammifère nécessitant ce type de traitement et/ou de prophylaxie, une quantité efficace et/ou prophylactique de BRL 38227.
PCT/GB1992/002141 1991-11-21 1992-11-19 Utilisation de brl 38227 pour le traitement et la prophylaxie de l'hyperlipidemie Ceased WO1993009778A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9124754.4 1991-11-21
GB919124754A GB9124754D0 (en) 1991-11-21 1991-11-21 Pharmaceuticals

Publications (2)

Publication Number Publication Date
WO1993009778A2 true WO1993009778A2 (fr) 1993-05-27
WO1993009778A3 WO1993009778A3 (fr) 1993-07-22

Family

ID=10705002

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1992/002141 Ceased WO1993009778A2 (fr) 1991-11-21 1992-11-19 Utilisation de brl 38227 pour le traitement et la prophylaxie de l'hyperlipidemie

Country Status (3)

Country Link
AU (1) AU2949592A (fr)
GB (1) GB9124754D0 (fr)
WO (1) WO1993009778A2 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8800199D0 (en) * 1988-01-06 1988-02-10 Beecham Group Plc Pharmaceutical preparation
GB8927980D0 (en) * 1989-12-11 1990-02-14 Beecham Group Plc Pharmaceuticals

Also Published As

Publication number Publication date
GB9124754D0 (en) 1992-01-15
WO1993009778A3 (fr) 1993-07-22
AU2949592A (en) 1993-06-15

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