EP0651642A1 - Use of 1,3-dicyclopropymethyl-8-amino-xanthine for the treatment and prevention of type ii diabetes mellitus and obesity - Google Patents
Use of 1,3-dicyclopropymethyl-8-amino-xanthine for the treatment and prevention of type ii diabetes mellitus and obesityInfo
- Publication number
- EP0651642A1 EP0651642A1 EP93917883A EP93917883A EP0651642A1 EP 0651642 A1 EP0651642 A1 EP 0651642A1 EP 93917883 A EP93917883 A EP 93917883A EP 93917883 A EP93917883 A EP 93917883A EP 0651642 A1 EP0651642 A1 EP 0651642A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- treatment
- compound
- obesity
- day
- type
- 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.)
- Withdrawn
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 30
- 208000008589 Obesity Diseases 0.000 title claims abstract description 13
- 235000020824 obesity Nutrition 0.000 title claims abstract description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 12
- 229940075420 xanthine Drugs 0.000 title abstract description 3
- 230000002265 prevention Effects 0.000 title description 2
- 229940125904 compound 1 Drugs 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000011321 prophylaxis Methods 0.000 claims abstract description 12
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 3
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 3
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 12
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 5
- 238000007911 parenteral administration Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000003981 vehicle Substances 0.000 description 11
- 235000012631 food intake Nutrition 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000037406 food intake Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 6
- 230000037396 body weight Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000031638 Body Weight Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- -1 colourants Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929215633A GB9215633D0 (en) | 1992-07-23 | 1992-07-23 | Novel treatment |
| GB9215633 | 1992-07-23 | ||
| PCT/GB1993/001539 WO1994002150A1 (en) | 1992-07-23 | 1993-07-21 | Use of 1,3-dicyclopropymethyl-8-amino-xanthine for the treatment and prevention of type ii diabetes mellitus and obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0651642A1 true EP0651642A1 (en) | 1995-05-10 |
Family
ID=10719151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP93917883A Withdrawn EP0651642A1 (en) | 1992-07-23 | 1993-07-21 | Use of 1,3-dicyclopropymethyl-8-amino-xanthine for the treatment and prevention of type ii diabetes mellitus and obesity |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0651642A1 (forum.php) |
| JP (1) | JPH07509456A (forum.php) |
| CN (1) | CN1043610C (forum.php) |
| AU (1) | AU4714393A (forum.php) |
| GB (1) | GB9215633D0 (forum.php) |
| MX (1) | MX9304435A (forum.php) |
| TW (1) | TW258663B (forum.php) |
| WO (1) | WO1994002150A1 (forum.php) |
| ZA (1) | ZA935339B (forum.php) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5783408A (en) * | 1995-06-07 | 1998-07-21 | Hamilton; Bradford S. | Method for screening potential anti-obesity agents |
| EA007485B1 (ru) * | 2001-02-24 | 2006-10-27 | Берингер Ингельхайм Фарма Гмбх Унд Ко. Кг | Производные ксантина, способ их получения, фармацевтическая композиция на их основе и способ ее получения |
| ATE388951T1 (de) * | 2001-07-03 | 2008-03-15 | Novo Nordisk As | Dpp-iv-inhibierende purin-derivative zur behandlung von diabetes |
| US6869947B2 (en) | 2001-07-03 | 2005-03-22 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme DPP-IV |
| EP1463727A2 (en) * | 2001-09-19 | 2004-10-06 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme dpp-iv |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| DE10254304A1 (de) * | 2002-11-21 | 2004-06-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| AU2004269923B2 (en) | 2003-09-05 | 2010-05-13 | Takeda Gmbh | Use of PDE4 inhibitors for the treatment of diabetes mellitus |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| DE102004030502A1 (de) | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| KR101302838B1 (ko) | 2005-03-08 | 2013-09-03 | 다케다 게엠베하 | 진성 당뇨병 치료용 로플루밀라스트 |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| BRPI0711558A2 (pt) | 2006-05-04 | 2011-11-08 | Boeringer Ingelheim Internat Gmbh | polimorfos |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| PE20140960A1 (es) | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| KR20200118243A (ko) | 2008-08-06 | 2020-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
| US8513264B2 (en) | 2008-09-10 | 2013-08-20 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| AU2009331471B2 (en) | 2008-12-23 | 2015-09-03 | Boehringer Ingelheim International Gmbh | Salt forms of organic compound |
| TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
| KR20240090632A (ko) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료 |
| PH12012502162A1 (en) | 2010-05-05 | 2013-02-04 | Boehringer Ingelheim Int | Combination therapy |
| WO2011161161A1 (en) | 2010-06-24 | 2011-12-29 | Boehringer Ingelheim International Gmbh | Diabetes therapy |
| US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
| DK3517539T3 (en) | 2011-07-15 | 2023-01-16 | Boehringer Ingelheim Int | Farmaceutiske sammensætninger til behandling af type i og type ii diabetes |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| EP3685839A1 (en) | 2012-05-14 | 2020-07-29 | Boehringer Ingelheim International GmbH | Linagliptin for use in the treatment of albuminuria and kidney related diseases |
| WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| US9526728B2 (en) | 2014-02-28 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Medical use of a DPP-4 inhibitor |
| EP3468562A1 (en) | 2016-06-10 | 2019-04-17 | Boehringer Ingelheim International GmbH | Combinations of linagliptin and metformin |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8906792D0 (en) * | 1989-03-23 | 1989-05-10 | Beecham Wuelfing Gmbh & Co Kg | Treatment and compounds |
-
1992
- 1992-07-23 GB GB929215633A patent/GB9215633D0/en active Pending
-
1993
- 1993-07-21 AU AU47143/93A patent/AU4714393A/en not_active Abandoned
- 1993-07-21 EP EP93917883A patent/EP0651642A1/en not_active Withdrawn
- 1993-07-21 JP JP6504294A patent/JPH07509456A/ja active Pending
- 1993-07-21 WO PCT/GB1993/001539 patent/WO1994002150A1/en not_active Application Discontinuation
- 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
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9402150A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA935339B (en) | 1995-01-18 |
| GB9215633D0 (en) | 1992-09-09 |
| AU4714393A (en) | 1994-02-14 |
| MX9304435A (es) | 1994-04-29 |
| WO1994002150A1 (en) | 1994-02-03 |
| CN1043610C (zh) | 1999-06-16 |
| TW258663B (forum.php) | 1995-10-01 |
| CN1114880A (zh) | 1996-01-17 |
| JPH07509456A (ja) | 1995-10-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1994002150A1 (en) | Use of 1,3-dicyclopropymethyl-8-amino-xanthine for the treatment and prevention of type ii diabetes mellitus and obesity | |
| KR100298807B1 (ko) | 파킨슨씨병및파킨슨증후군의치료를위한,리루졸을포함하는제약학적조성물 | |
| US5521198A (en) | Methods of inhibiting autoimmune diseases | |
| SK170999A3 (en) | Compositions for treating and preventing arterial thrombosis and use of a factor xa inhibitor on its own and/or combined with a platelet antiaggregating agent | |
| HUT71477A (en) | Pharmaceutical compositions for increasing libido in post-menopausal women containing 2-phenyl-3-aroil-benzothiophene derivatives and process for their preparation | |
| HUT71469A (en) | Pharmaceutical compositions for inhibiting dysfunctional uterine bleeding containing 2-phenyl-3-aroyl-benzothiophene derivatives and process for their preparation | |
| US4657910A (en) | Treatment of cerebrovascular disorders and/or disorders associated with cerebral senility | |
| CA2126354C (en) | Use of 5-ht4 modulators for the manufacture of a medicament for the treatment of the bladder diseases | |
| AU653521B2 (en) | Use of 5-HT4 receptor antagonists in the treatment of arrythmias and stroke | |
| CA1069441A (en) | Pharmaceutical composition containing 2,1,3-benzothiazole | |
| SK15472001A3 (sk) | Použitie saredutantu a jeho farmaceuticky prijateľných solí na prípravu liečiva použiteľného na liečenie alebo prevenciu porúch nálady, porúch adaptácie alebo stavov úzkosti a depresie | |
| AU706594B2 (en) | Treatment of traumatic brain injury | |
| US5049588A (en) | Novel treatment for ischemia using an aminotetralin | |
| US6514980B1 (en) | Nucleoside analogs in combination therapy of herpes simplex infections | |
| US5162375A (en) | Treatment of neuronal degeneration with 5HT1A agonists | |
| DK169305B1 (da) | Anvendelse af propentofyllin og beslægtede forbindelser til fremstilling af et terapeutisk middel til behandling af peptisk ulcus | |
| US3462534A (en) | Production of an antidepressant effect with esters of gallic acid | |
| US6750195B2 (en) | Use of 5-HT4 modulators for the manufacture of a medicament for the treatment of the bladder diseases | |
| US3933999A (en) | Organic compounds | |
| EP0254068B1 (en) | Novel therapeutic agent for gastritis | |
| US4363809A (en) | Organic compounds | |
| US4956362A (en) | Use of carpipramine for the treatment of anxiety and sleep disorders | |
| US4988720A (en) | Novel treatment of hyperglycaemia | |
| HUP0103149A2 (hu) | Gyógyszerkészítmény Alzheimer-kór kezelésére | |
| US5238946A (en) | Therapeutic agent for gastritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19950123 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): BE CH DE FR GB IE IT LI NL |
|
| 17Q | First examination report despatched |
Effective date: 19960115 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19960529 |