CA2065151A1 - Preparations containing colestyramine for reducing lipid levels - Google Patents
Preparations containing colestyramine for reducing lipid levelsInfo
- Publication number
- CA2065151A1 CA2065151A1 CA002065151A CA2065151A CA2065151A1 CA 2065151 A1 CA2065151 A1 CA 2065151A1 CA 002065151 A CA002065151 A CA 002065151A CA 2065151 A CA2065151 A CA 2065151A CA 2065151 A1 CA2065151 A1 CA 2065151A1
- Authority
- CA
- Canada
- Prior art keywords
- colestyramine
- lipid
- preparations containing
- lipid levels
- lowering agents
- 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.)
- Abandoned
Links
- KNDHRUPPBXRELB-UHFFFAOYSA-M [4-[3-(4-ethylphenyl)butyl]phenyl]-trimethylazanium;chloride Chemical compound [Cl-].C1=CC(CC)=CC=C1C(C)CCC1=CC=C([N+](C)(C)C)C=C1 KNDHRUPPBXRELB-UHFFFAOYSA-M 0.000 title claims abstract description 22
- 229960001678 colestyramine Drugs 0.000 title claims abstract description 22
- 229920001268 Cholestyramine Polymers 0.000 title claims abstract description 20
- 150000002632 lipids Chemical class 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title 1
- 239000003524 antilipemic agent Substances 0.000 claims abstract description 15
- 239000002245 particle Substances 0.000 claims description 8
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 3
- 229960002297 fenofibrate Drugs 0.000 claims description 3
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 3
- 229960003627 gemfibrozil Drugs 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 8
- 229960003732 tyramine Drugs 0.000 description 8
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 7
- 229940125753 fibrate Drugs 0.000 description 7
- DZGWFCGJZKJUFP-UHFFFAOYSA-O tyraminium Chemical compound [NH3+]CCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-O 0.000 description 7
- 239000003814 drug Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 229960000516 bezafibrate Drugs 0.000 description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960001214 clofibrate Drugs 0.000 description 2
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- ZMJBYMUCKBYSCP-UHFFFAOYSA-N Hydroxycitric acid Chemical compound OC(=O)C(O)C(O)(C(O)=O)CC(O)=O ZMJBYMUCKBYSCP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia 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
- 150000001450 anions Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229950009252 beclobrate Drugs 0.000 description 1
- YWQGBCXVCXMSLJ-UHFFFAOYSA-N beclobrate Chemical compound C1=CC(OC(C)(CC)C(=O)OCC)=CC=C1CC1=CC=C(Cl)C=C1 YWQGBCXVCXMSLJ-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960002174 ciprofibrate Drugs 0.000 description 1
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960003501 etofibrate Drugs 0.000 description 1
- XXRVYAFBUDSLJX-UHFFFAOYSA-N etofibrate Chemical compound C=1C=CN=CC=1C(=O)OCCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 XXRVYAFBUDSLJX-UHFFFAOYSA-N 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000008016 pharmaceutical coating Substances 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- -1 pre~ervatives Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- 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
- A61P3/06—Antihyperlipidemics
Abstract
Colestyramine as products containing lipid-lowering agents Abstract of the disclosure Colestyramine as products containing lipid-lowering agents
Description
2 ~
O.Z. 0480/01072 Colestyramine as products containing lipid-lowering agents Description The present invention relates to colestyramine a~
products which contain lipid-lowering agents and are in the form of particles whose longest particle diameter is fxom 1 to 6 mm.
ColestyraminQ is a lipid-lowering agent known in medicine and i8 an anion exchanger resin composed of a copolymer of styrene and divinylbenzene which contain~
quaternary ammonium group~.
To date it has been market~d only as powder ~see Rote Liste 19~0, li~t of finished drug~ of the member~ of the Bundesverband der Pharmazeutischen Industrie e.V.).
One disadvantage of this presentation is that, on intake, cole~tyramine leaves an unpleasant sandy taste in the mouth (see, for example, Rnodel ~t al., Medical Toxi-colo~y 2 (lg87) 10, page 13, first paragraph o~ Section 1.2 in which the di~advantageou~ effects of lipid-lowering agents are dealt with). Since it is now cu~-tomary for colestyrsmine to have to be taXan in single do~es of about 4 g twica to eight.times a day, this frequently results in the patients taking 1 S8 than the prescribed dose or eve~ ~topping the therapy with coles-tyramine ~3ee EP-A 261 6g3, pag 2, line 7 8).
There has been no lack of attempt~ to offer colestyr~mine in a dif~erent presentation. Thu~, VS-A
4,814,354 de~cribe~ colestyramine-containing s~eet~, EP-A 347 014 descxibes a baked product containing c012~-tyramine, and DE-A 38 08 191 describe~ aqueous colestyræmine-containing suspen~ion3. However, it i8 not pos~ible in thi~ way to eliminate the unpleasant sandy taste.
It is furthermore known that cole~tyramine can be administer2d to~ether with other lipid-lowering agent~ in : ~ :: :
0~2. 04B0/01072 - 2 -order to achieve an effect which is better than that of the ~ingle component~. Malmendier et al~ (Clin. ChLm.
Acta 162 tl987~ 221), as well as Carlson et al. (in ~ITreatment of Hyperlipoproteinaemia", XIX + 284P. Raven Press: New York 1984) describe the combined use of colestyramine and fenofibrate in patients with hereditary hypercholesterolemia. The combined use of colestyramine and bezafibrate i~ described, for example, in Br. Med. J.
297 (1988) 6642, the combined u~e of colestyramine and clofibrate for example in J. Lipid Re~. 21 (1980) 65 and the combined u~e of colestyramine and gemfibrozil in US-A 4,814,354.
The object on which the invention was based was to prepare colestyramine as product~ which contain lipid-lowering agents and are in a prs~entation, which do not display the abovementioned disadvantage~.
Accordingly, colestyramine as products which contain lipid-lowering agents have been found in the form of particles whose longest particle diameter i~ from 1 to 6 mm.
Colestyr~mine can be compressed to particle~ with a longe~t pArticle diameter of from 1 to 6 mm. A pre-ferred form is the so-called microtablet which, a~ a rula, i5 cylindrical and has a size of from 1 to 4 mm (~oth height and diameter), in particular of fro~ 2.0 to 3.5 mm. Be~ides this, other forms su~h as bead or irregularly ~haped granule~ are also possi~le in principle.
The forms can be produced in a conven~ional manner, for e~ampl2 that described in EP-A 166 315. It i8 po~sib~e to add the conventional pharmaceutical auxili-arie~ to the formulation,` ~uch a~ binder~, inactive ingredients, pre~ervatives, wetting agents, flow regula-tor~, lubricant~ and/or antioxidants (see, for example, H. ~ucker et al.: Pharma~euti~che ~echnologie", ~hieme ~erlag Stuttgart, (1378)). The form8 can additionally be provided with the conventional pharmaceutical coating~.
.
.:: , ' ' , ' : : ` ~ . ` , ' :, :
, .
2~1 5~
O.Z. 0480~01072 - 3 -The preferred binder used for compression is microcrystalline cellulosP, of which the drug con~ains from 2 to 20, preferably fLom 3 to 8, ~ by weight. It is advantageous to employ in the granulation cellulo~e derivatives such as methylcellulose, hydroxypropylmethyl-cellulose, hydro~yethylcellulosQ and polyvinylpyrrolidone in an amount of from 2 to 10, preferably 3 to 6, % by wei~ht.
The fonmulations obtainable in this way normally contain the active compound in an amount of from 80 to 99% by weight.
~he dosage depends on the age, condition and weight of the patient. As a rule, ths daily dose of active compou~d is between 0.03 and 0.4 g/kg. of body weight.
The cole~tyramine-containing product~ can al80 contain other lipid-lowering agents. Fenofibrate and gemfibrozil are preferred, a~ are ~imilar compound~ of this type ~uch a~ clofibrate, beclobrate, bezafibrate, ciprofibrate and etofibrate (called fibrates herein-after).
The drug on administration can be a combination of the two active compounds in the same formulation or be in the form of a so-called kit o~E parts. A kit of parts is defined a~ a type of pharmaceutical pack in which the indi~idual active componsnt~ are pre~ent wholly or partly in ~eparate dose ~or~ in the ~ame pack.
The form pre~erred for the combination of the active compound~ in the ~ame form is ~he microtablet. In the case of separate admini~tration, the cole~tyramine i8 preferably in the microtablet form~ and the fibrate i~ in a con~entional commerclal form ~uch a~ tablet, film-coated tablet, ~ugar-coa~ed tablet, capsule or else a~
microtablet.
The ~tatements on the formulation of colestyr-amine al30 apply to the combination of cole~tyramine and fibrate.
s ' ~'~ ' '' ' :: ~: '' :, . . : ' '.. ; . :
:. .. :'~ ', :
,, : ~ - ,. ' :~
.. ' ' ,. ~' '; ', .
2 ~
O.Z. 04aO/01072 - 4 -When cole~tyramine and fibrate ~re combined in one form, for example as micro~ablet, the latter can contain the active compounds in the colestyramine fibrate ratio of from 2 : 1 to 99 s 1 by weigh~, depend-S ing on the conventional dose of the fibrate active : co~pound.
Combina~ion of the two active compounds makes it possible to lower the individual doses of these active compounds, the dosage depending specifically on th~ age, condition and weight of the patient. In general~ the daily do~e~ of active compound~ are betw~en 0.03 and 0.4 g of colestyramine per kg of body weight and between 1 and lS mg of fibrate per kg of body weight.
Ex2mples Example 1 13.5 kg of colestyramine (from R~hm & Haas Deut~chland GmbH, cole~tyramine 40 ~) were mixed with 675 g of directly tablettable lactose and 600 g of microcrystalline ~elluIo~e in a ~onventional high-2G performance pharmaceutical mixer. Then 75 g of highlydi~per~e ilica and 150 g of magne~ium stearate were added, and mixing was continued. ~his mixture for comp-ression was then compre~sed to microtablets with a diam~ter of 3.5 mm and the sa~a height, the indiYidual ma~ being 30 mg.
Example 2 13.5 kg o colestyramine (see above) were mixed with a solution o 0.7 kg of polyvinylpyrrolidone (mean molecular mas~ ~S0OOO) in 2.1 kg of iBopropanol in a ; 3~ conventional high-performance pharmaceutical mixer with cutter, and were gr~nlllated. Drying at 50C wa~ followed by ~creening through an oscillating screen with a me~h width of 0.8 mm. The granules were then mixed with 70 g of highly di~per~e Rilica and 70 g of magne~ium ~tearate.
The co~po~ition rea~y for compression wa~ compres~ed to microtablets with a diameter of 3 mm and the ~ame height, the individual mas~ being 17 mg.
- - ........ . .
- . - . .
.: - ~. : . :
, , :.: . ~ :, : . ~ ,, : , . :
. : ,. ~ .
, -: :
~, i ..
~ . : ,.
O.Z. 0480/01072 Colestyramine as products containing lipid-lowering agents Description The present invention relates to colestyramine a~
products which contain lipid-lowering agents and are in the form of particles whose longest particle diameter is fxom 1 to 6 mm.
ColestyraminQ is a lipid-lowering agent known in medicine and i8 an anion exchanger resin composed of a copolymer of styrene and divinylbenzene which contain~
quaternary ammonium group~.
To date it has been market~d only as powder ~see Rote Liste 19~0, li~t of finished drug~ of the member~ of the Bundesverband der Pharmazeutischen Industrie e.V.).
One disadvantage of this presentation is that, on intake, cole~tyramine leaves an unpleasant sandy taste in the mouth (see, for example, Rnodel ~t al., Medical Toxi-colo~y 2 (lg87) 10, page 13, first paragraph o~ Section 1.2 in which the di~advantageou~ effects of lipid-lowering agents are dealt with). Since it is now cu~-tomary for colestyrsmine to have to be taXan in single do~es of about 4 g twica to eight.times a day, this frequently results in the patients taking 1 S8 than the prescribed dose or eve~ ~topping the therapy with coles-tyramine ~3ee EP-A 261 6g3, pag 2, line 7 8).
There has been no lack of attempt~ to offer colestyr~mine in a dif~erent presentation. Thu~, VS-A
4,814,354 de~cribe~ colestyramine-containing s~eet~, EP-A 347 014 descxibes a baked product containing c012~-tyramine, and DE-A 38 08 191 describe~ aqueous colestyræmine-containing suspen~ion3. However, it i8 not pos~ible in thi~ way to eliminate the unpleasant sandy taste.
It is furthermore known that cole~tyramine can be administer2d to~ether with other lipid-lowering agent~ in : ~ :: :
0~2. 04B0/01072 - 2 -order to achieve an effect which is better than that of the ~ingle component~. Malmendier et al~ (Clin. ChLm.
Acta 162 tl987~ 221), as well as Carlson et al. (in ~ITreatment of Hyperlipoproteinaemia", XIX + 284P. Raven Press: New York 1984) describe the combined use of colestyramine and fenofibrate in patients with hereditary hypercholesterolemia. The combined use of colestyramine and bezafibrate i~ described, for example, in Br. Med. J.
297 (1988) 6642, the combined u~e of colestyramine and clofibrate for example in J. Lipid Re~. 21 (1980) 65 and the combined u~e of colestyramine and gemfibrozil in US-A 4,814,354.
The object on which the invention was based was to prepare colestyramine as product~ which contain lipid-lowering agents and are in a prs~entation, which do not display the abovementioned disadvantage~.
Accordingly, colestyramine as products which contain lipid-lowering agents have been found in the form of particles whose longest particle diameter i~ from 1 to 6 mm.
Colestyr~mine can be compressed to particle~ with a longe~t pArticle diameter of from 1 to 6 mm. A pre-ferred form is the so-called microtablet which, a~ a rula, i5 cylindrical and has a size of from 1 to 4 mm (~oth height and diameter), in particular of fro~ 2.0 to 3.5 mm. Be~ides this, other forms su~h as bead or irregularly ~haped granule~ are also possi~le in principle.
The forms can be produced in a conven~ional manner, for e~ampl2 that described in EP-A 166 315. It i8 po~sib~e to add the conventional pharmaceutical auxili-arie~ to the formulation,` ~uch a~ binder~, inactive ingredients, pre~ervatives, wetting agents, flow regula-tor~, lubricant~ and/or antioxidants (see, for example, H. ~ucker et al.: Pharma~euti~che ~echnologie", ~hieme ~erlag Stuttgart, (1378)). The form8 can additionally be provided with the conventional pharmaceutical coating~.
.
.:: , ' ' , ' : : ` ~ . ` , ' :, :
, .
2~1 5~
O.Z. 0480~01072 - 3 -The preferred binder used for compression is microcrystalline cellulosP, of which the drug con~ains from 2 to 20, preferably fLom 3 to 8, ~ by weight. It is advantageous to employ in the granulation cellulo~e derivatives such as methylcellulose, hydroxypropylmethyl-cellulose, hydro~yethylcellulosQ and polyvinylpyrrolidone in an amount of from 2 to 10, preferably 3 to 6, % by wei~ht.
The fonmulations obtainable in this way normally contain the active compound in an amount of from 80 to 99% by weight.
~he dosage depends on the age, condition and weight of the patient. As a rule, ths daily dose of active compou~d is between 0.03 and 0.4 g/kg. of body weight.
The cole~tyramine-containing product~ can al80 contain other lipid-lowering agents. Fenofibrate and gemfibrozil are preferred, a~ are ~imilar compound~ of this type ~uch a~ clofibrate, beclobrate, bezafibrate, ciprofibrate and etofibrate (called fibrates herein-after).
The drug on administration can be a combination of the two active compounds in the same formulation or be in the form of a so-called kit o~E parts. A kit of parts is defined a~ a type of pharmaceutical pack in which the indi~idual active componsnt~ are pre~ent wholly or partly in ~eparate dose ~or~ in the ~ame pack.
The form pre~erred for the combination of the active compound~ in the ~ame form is ~he microtablet. In the case of separate admini~tration, the cole~tyramine i8 preferably in the microtablet form~ and the fibrate i~ in a con~entional commerclal form ~uch a~ tablet, film-coated tablet, ~ugar-coa~ed tablet, capsule or else a~
microtablet.
The ~tatements on the formulation of colestyr-amine al30 apply to the combination of cole~tyramine and fibrate.
s ' ~'~ ' '' ' :: ~: '' :, . . : ' '.. ; . :
:. .. :'~ ', :
,, : ~ - ,. ' :~
.. ' ' ,. ~' '; ', .
2 ~
O.Z. 04aO/01072 - 4 -When cole~tyramine and fibrate ~re combined in one form, for example as micro~ablet, the latter can contain the active compounds in the colestyramine fibrate ratio of from 2 : 1 to 99 s 1 by weigh~, depend-S ing on the conventional dose of the fibrate active : co~pound.
Combina~ion of the two active compounds makes it possible to lower the individual doses of these active compounds, the dosage depending specifically on th~ age, condition and weight of the patient. In general~ the daily do~e~ of active compound~ are betw~en 0.03 and 0.4 g of colestyramine per kg of body weight and between 1 and lS mg of fibrate per kg of body weight.
Ex2mples Example 1 13.5 kg of colestyramine (from R~hm & Haas Deut~chland GmbH, cole~tyramine 40 ~) were mixed with 675 g of directly tablettable lactose and 600 g of microcrystalline ~elluIo~e in a ~onventional high-2G performance pharmaceutical mixer. Then 75 g of highlydi~per~e ilica and 150 g of magne~ium stearate were added, and mixing was continued. ~his mixture for comp-ression was then compre~sed to microtablets with a diam~ter of 3.5 mm and the sa~a height, the indiYidual ma~ being 30 mg.
Example 2 13.5 kg o colestyramine (see above) were mixed with a solution o 0.7 kg of polyvinylpyrrolidone (mean molecular mas~ ~S0OOO) in 2.1 kg of iBopropanol in a ; 3~ conventional high-performance pharmaceutical mixer with cutter, and were gr~nlllated. Drying at 50C wa~ followed by ~creening through an oscillating screen with a me~h width of 0.8 mm. The granules were then mixed with 70 g of highly di~per~e Rilica and 70 g of magne~ium ~tearate.
The co~po~ition rea~y for compression wa~ compres~ed to microtablets with a diameter of 3 mm and the ~ame height, the individual mas~ being 17 mg.
- - ........ . .
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Claims (3)
1. Colestyramine as products which contain lipid-lowering agents and are in the form of particles whose longest particle diameter is from 1 to 6 mm.
2. Colestyramine as products which contain lipid-lowering agents as claimed in claim 1, containing another lipid-lowering agent in addition to the colestyramine.
3. Colestyramine a products which contain lipid-lowering agents as claimed in claim 2, containing feno-fibrate or gemfibrozil as further lipid-lowering agent.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19893930206 DE3930206A1 (en) | 1989-09-09 | 1989-09-09 | Hypolipaemic pharmaceutical prods. - comprising combination of cholestyramine and drug of vibrate type |
| DE3930168A DE3930168A1 (en) | 1989-09-09 | 1989-09-09 | Pharmaceutical compsn. contg. colestyramine to reduce lipid - in micro:tablet form levels without unpleasant taste |
| DEP3930168.0 | 1989-09-09 | ||
| DEP3930206.7 | 1989-09-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2065151A1 true CA2065151A1 (en) | 1991-03-10 |
Family
ID=25884990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002065151A Abandoned CA2065151A1 (en) | 1989-09-09 | 1990-09-07 | Preparations containing colestyramine for reducing lipid levels |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0594570B1 (en) |
| JP (1) | JPH05500213A (en) |
| KR (1) | KR920703071A (en) |
| AT (1) | ATE125448T1 (en) |
| AU (1) | AU638493B2 (en) |
| CA (1) | CA2065151A1 (en) |
| DE (1) | DE59009451D1 (en) |
| DK (1) | DK0594570T3 (en) |
| IL (1) | IL95574A (en) |
| WO (1) | WO1991003249A1 (en) |
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|---|---|---|---|---|
| US20170224720A1 (en) * | 2016-02-09 | 2017-08-10 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10000528B2 (en) | 2010-11-08 | 2018-06-19 | Albireo Ab | IBAT inhibitors for the treatment of liver diseases |
| US10183920B2 (en) | 2014-10-24 | 2019-01-22 | Elobix Ab | Crystal modifications of elobixibat |
| US10441605B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10441604B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
| CN110996915A (en) * | 2017-08-09 | 2020-04-10 | 阿尔比里奥公司 | Colestyramine pellets, oral colestyramine formulations and uses thereof |
| US10709755B2 (en) | 2014-06-25 | 2020-07-14 | Elobix Ab | Solid formulation and method for preventing or reducing coloration thereof |
| US10722457B2 (en) | 2018-08-09 | 2020-07-28 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10793534B2 (en) | 2018-06-05 | 2020-10-06 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US10881685B2 (en) | 2017-08-09 | 2021-01-05 | Albireo Ab | Cholestyramine granules, oral cholestyramine formulations and use thereof |
| US10975046B2 (en) | 2018-06-20 | 2021-04-13 | Albireo Ab | Crystal modifications of odevixibat |
| US11007142B2 (en) | 2018-08-09 | 2021-05-18 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US11549878B2 (en) | 2018-08-09 | 2023-01-10 | Albireo Ab | In vitro method for determining the adsorbing capacity of an insoluble adsorbant |
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| CA3011565C (en) * | 2016-02-09 | 2024-01-02 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| WO2017138876A1 (en) * | 2016-02-09 | 2017-08-17 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
| WO2017138878A1 (en) * | 2016-02-09 | 2017-08-17 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| ES2942443T3 (en) | 2018-06-05 | 2023-06-01 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US11801226B2 (en) | 2018-06-20 | 2023-10-31 | Albireo Ab | Pharmaceutical formulation of odevixibat |
| US10975045B2 (en) | 2019-02-06 | 2021-04-13 | Aibireo AB | Benzothiazepine compounds and their use as bile acid modulators |
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| CN114761018A (en) | 2019-12-04 | 2022-07-15 | 阿尔比里奥公司 | Benzothiadiazepine compounds and their use as bile acid modulators |
| EP4069361B1 (en) | 2019-12-04 | 2024-01-03 | Albireo AB | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US11014898B1 (en) | 2020-12-04 | 2021-05-25 | Albireo Ab | Benzothiazepine compounds and their use as bile acid modulators |
| CA3158276A1 (en) | 2019-12-04 | 2021-06-10 | Per-Goran Gillberg | Benzothia(di)azepine compounds and their use as bile acid modulators |
| CR20220315A (en) | 2019-12-04 | 2022-10-26 | Albireo Ab | BENZOTI(DI)AZEPINE COMPOUNDS AND THEIR USE AS BILE ACID MODULATORS |
| JP2023537285A (en) | 2020-08-03 | 2023-08-31 | アルビレオ・アクチボラグ | Benzothia(di)azepine compounds and their use as bile acid modulators |
| CA3196488A1 (en) | 2020-11-12 | 2022-05-19 | Albireo Ab | Odevixibat for treating progressive familial intrahepatic cholestasis (pfic) |
| KR20230117393A (en) | 2020-12-04 | 2023-08-08 | 알비레오 에이비 | Benzothia(di)azepine compounds and their use as bile acid regulators |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1348642A (en) * | 1970-10-15 | 1974-03-20 | Howard A N | Hypocholesterolaemic compositions |
| GB1566609A (en) | 1977-03-10 | 1980-05-08 | Reckitt & Colmann Prod Ltd | Pharmaceutical compositions containing cholestyramine and alginic acid |
| EP0166315B1 (en) | 1984-06-19 | 1989-08-23 | BASF Aktiengesellschaft | Gastro-resistant cylindrical pancreatine-microtablets |
| US4814354A (en) * | 1986-09-26 | 1989-03-21 | Warner-Lambert Company | Lipid regulating agents |
| ZA876640B (en) | 1986-09-26 | 1988-03-08 | Warner-Lambert Company | Treated lipid regulator |
| CA1313135C (en) * | 1987-02-09 | 1993-01-26 | The Dow Chemical Company | Cholestyramine composition and process for its preparation |
| DE3869590D1 (en) * | 1987-12-29 | 1992-04-30 | Procter & Gamble | MIXTURE FOR TREATING HYPERCHOLESTEROLEMY. |
| DE3808191C2 (en) | 1988-03-11 | 1998-08-06 | Astra Chem Gmbh | Pharmaceutical composition containing colestyramine |
| US4931280A (en) | 1988-06-13 | 1990-06-05 | Basf K & F Corporation | Edible, baked compositions containing cholestyramine |
-
1990
- 1990-09-04 IL IL9557490A patent/IL95574A/en not_active IP Right Cessation
- 1990-09-07 DK DK90913811.7T patent/DK0594570T3/en active
- 1990-09-07 KR KR1019920700526A patent/KR920703071A/en not_active Application Discontinuation
- 1990-09-07 AU AU64057/90A patent/AU638493B2/en not_active Ceased
- 1990-09-07 CA CA002065151A patent/CA2065151A1/en not_active Abandoned
- 1990-09-07 WO PCT/EP1990/001514 patent/WO1991003249A1/en active IP Right Grant
- 1990-09-07 AT AT90913811T patent/ATE125448T1/en not_active IP Right Cessation
- 1990-09-07 JP JP2512849A patent/JPH05500213A/en active Pending
- 1990-09-07 DE DE59009451T patent/DE59009451D1/en not_active Expired - Lifetime
- 1990-09-07 EP EP90913811A patent/EP0594570B1/en not_active Expired - Lifetime
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| US10000528B2 (en) | 2010-11-08 | 2018-06-19 | Albireo Ab | IBAT inhibitors for the treatment of liver diseases |
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| US10793534B2 (en) | 2018-06-05 | 2020-10-06 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US10975046B2 (en) | 2018-06-20 | 2021-04-13 | Albireo Ab | Crystal modifications of odevixibat |
| US11802115B2 (en) | 2018-06-20 | 2023-10-31 | Albireo Ab | Pharmaceutical formulation of odevixibat |
| US11549878B2 (en) | 2018-08-09 | 2023-01-10 | Albireo Ab | In vitro method for determining the adsorbing capacity of an insoluble adsorbant |
| US11007142B2 (en) | 2018-08-09 | 2021-05-18 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10722457B2 (en) | 2018-08-09 | 2020-07-28 | Albireo Ab | Oral cholestyramine formulation and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| AU638493B2 (en) | 1993-07-01 |
| ATE125448T1 (en) | 1995-08-15 |
| WO1991003249A1 (en) | 1991-03-21 |
| IL95574A (en) | 1994-11-11 |
| IL95574A0 (en) | 1991-06-30 |
| KR920703071A (en) | 1992-12-17 |
| JPH05500213A (en) | 1993-01-21 |
| DK0594570T3 (en) | 1995-09-11 |
| AU6405790A (en) | 1991-04-08 |
| EP0594570A1 (en) | 1994-05-04 |
| EP0594570B1 (en) | 1995-07-26 |
| DE59009451D1 (en) | 1995-08-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |