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
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
  • A61K31/52—Purines, e.g. adenine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
  • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

• the present invention relates to a method for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes and a compound for use in such method.
• R* and R ⁇ each independendy represent alkyl or a moiety of formula (a):
• A represents a substituted or unsubstituted cyclic hydrocarbon radical, providing that when R- represents methyl then R is not methyl;
• R3a represents a halogen atom, a nitro group, or a group -NR4R5 wherein R4 and R ⁇ each independently represent hydrogen, alkyl or alkylcarbonyl or R ⁇ and R5 together with the nitrogen to which they are attached form an optionally substituted heterocyclic group.
• Example 9 of EP 903030930.0 is 1,3-di-cyclopropymethyl- 8-amino xanthine (hereinafter preferred to as Compound 1).
• the compounds in European application No. 90303093.0 are described inter alia as having activity in the treatment of cerebral vascular and neuronal degenerative disease and to act as phosphodiesterase inhibitors elevating cyclic AMP levels.
• Compound 1 increases energy expenditure and also decreases food intake and is therefore of potential use in the treatment of obesity in mammals, including humans.
• Compound I is also indicated to be effective in improving insulin sensitivity and hence to be effective in the treatment of Type II diabetes.
• the present invention provides a method for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes in mammals, such as humans, which comprises administering to the mammal in need of such treatment and/or prophylaxis an effective and/or prophylactic, non-toxic amount of Compound 1.
• the present invention also provides Compound 1 for use in the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes.
• a pharmaceutical composition for use in the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes which comprises Compound 1 and a pharmaceutically acceptable carrier.
• the present invention provides the use of Compound 1 for the manufacture of a medicament for the treatment and/or prophylaxis of obesity or for the treatment of Type II diabetes.
• the administration to the mammal may be by way of oral administration or parenteral administration.
• a unit dose will normally contain 0.1 to 200 mg for example 5 to 50 mg or 1 to 20 mg, of Compound 1.
• Unit doses will normally be administered once or more than once a day, for example 1, 2, 3, 4, 5 or 6 times a day, more usually 1 to 4 times a day, such that the total daily dose is normally in the range, for a 70 kg adult of 0.5 to 500 mg, for example 50 to 250 mg or 10 to 150 mg, that is in the range of approximately 0.001 to 10 mg kg day, more usually 1 to 3 mg/kg day or 0.2 to 2.5 mg/kg/day, for example 0.7 to 2 mg/kg/day.
• Compound 1 is administered in the form of a unit-dose composition, such as a unit dose oral or parenteral composition.
• a unit dose composition such as a unit dose oral or parenteral composition.
• Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, 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.
• 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, diluents, tabletting agents, lubricants, disintegrants, colourants, 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, 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.
• solid oral compositions may be prepared by conventional methods of blending, filling, tabletting or the like. 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 j>-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
• 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 monoole
• Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
• fluid unit dose forms are prepared containing Compound 1 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.
• test animals were 12 male and 12 female, Sprague-Dawley rats (body weights 200-270g, approximately 8-10 weeks of age).
• the rats were fed on SQC rat and mouse maintenance diet No. 1; diet and drinking water were freely available.
• test compound was administered orally to the treatment group by oesophageal gavage as a suspension in 1% aqueous methylcellulose at a dose level of 1 mg/kg/day. Animals were dosed at a constant dose volume of lml/lOOg of bodyweight.
• mice Female CFLP mice (29-37g) were fed ad libitium on a pelleted diet and housed in pairs on a light cycle in which lights were off from 6pm to 6am. Compound 1 or vehicle was given at 2pm and food intake and body weight changes were measured over the following 20 hours. Results are means ⁇ SEM of 5 (food intake) or 10 (body weight) values.

Landscapes

• Health & Medical Sciences (AREA)
• Diabetes (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Bioinformatics & Cheminformatics (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Obesity (AREA)
• Hematology (AREA)
• Engineering & Computer Science (AREA)
• Endocrinology (AREA)
• Emergency Medicine (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (3)

Applications Claiming Priority (2)

Publications (1)

Family

ID=10719151

Family Applications (1)

Country Status (9)

Cited By (32)

Families Citing this family (1)

Citations (1)

• 1992
  • 1992-07-23 GB GB929215633A patent/GB9215633D0/en active Pending
• 1993
  • 1993-07-21 WO PCT/GB1993/001539 patent/WO1994002150A1/en not_active Application Discontinuation
  • 1993-07-21 JP JP6504294A patent/JPH07509456A/ja active Pending
  • 1993-07-21 EP EP93917883A patent/EP0651642A1/en not_active Withdrawn
  • 1993-07-21 AU AU47143/93A patent/AU4714393A/en not_active Abandoned
  • 1993-07-22 CN CN93116874A patent/CN1043610C/zh not_active Expired - Lifetime
  • 1993-07-22 MX MX9304435A patent/MX9304435A/es unknown
  • 1993-07-23 ZA ZA935339A patent/ZA935339B/xx unknown
  • 1993-07-27 TW TW082105967A patent/TW258663B/zh not_active IP Right Cessation

Patent Citations (1)

Non-Patent Citations (2)

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