NO323814B1 - Therapeutic combination in galenic unit tablet form. - Google Patents
Therapeutic combination in galenic unit tablet form. Download PDFInfo
- Publication number
- NO323814B1 NO323814B1 NO19971356A NO971356A NO323814B1 NO 323814 B1 NO323814 B1 NO 323814B1 NO 19971356 A NO19971356 A NO 19971356A NO 971356 A NO971356 A NO 971356A NO 323814 B1 NO323814 B1 NO 323814B1
- Authority
- NO
- Norway
- Prior art keywords
- calcium
- vitamin
- combination
- stated
- binder
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 8
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims abstract description 49
- 239000011575 calcium Substances 0.000 claims abstract description 41
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 39
- 235000019166 vitamin D Nutrition 0.000 claims abstract description 34
- 239000011710 vitamin D Substances 0.000 claims abstract description 34
- 229930003316 Vitamin D Natural products 0.000 claims abstract description 33
- 229940046008 vitamin d Drugs 0.000 claims abstract description 33
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 32
- 239000011230 binding agent Substances 0.000 claims abstract description 16
- 239000003085 diluting agent Substances 0.000 claims abstract description 10
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 7
- 239000000314 lubricant Substances 0.000 claims abstract description 7
- 239000003765 sweetening agent Substances 0.000 claims abstract description 7
- 229960005069 calcium Drugs 0.000 claims description 35
- 229910052791 calcium Inorganic materials 0.000 claims description 35
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 30
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 16
- 235000005282 vitamin D3 Nutrition 0.000 claims description 16
- 239000011647 vitamin D3 Substances 0.000 claims description 16
- 229940021056 vitamin d3 Drugs 0.000 claims description 16
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 15
- 229960003563 calcium carbonate Drugs 0.000 claims description 15
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical group OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 13
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 12
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 12
- 239000000811 xylitol Substances 0.000 claims description 12
- 235000010447 xylitol Nutrition 0.000 claims description 12
- 229960002675 xylitol Drugs 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 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 claims description 9
- 239000000600 sorbitol Substances 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 159000000007 calcium salts Chemical class 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 229960002061 ergocalciferol Drugs 0.000 claims description 4
- 235000001892 vitamin D2 Nutrition 0.000 claims description 4
- 239000011653 vitamin D2 Substances 0.000 claims description 4
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 claims description 4
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 239000001736 Calcium glycerylphosphate Substances 0.000 claims description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 239000002535 acidifier Substances 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 229960002713 calcium chloride Drugs 0.000 claims description 2
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 claims description 2
- 239000001354 calcium citrate Substances 0.000 claims description 2
- 229960004256 calcium citrate Drugs 0.000 claims description 2
- 229960002562 calcium glucoheptonate Drugs 0.000 claims description 2
- 239000004227 calcium gluconate Substances 0.000 claims description 2
- 229960004494 calcium gluconate Drugs 0.000 claims description 2
- 235000013927 calcium gluconate Nutrition 0.000 claims description 2
- 229940095618 calcium glycerophosphate Drugs 0.000 claims description 2
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 claims description 2
- 235000019299 calcium glycerylphosphate Nutrition 0.000 claims description 2
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 2
- 239000001527 calcium lactate Substances 0.000 claims description 2
- 229960002401 calcium lactate Drugs 0.000 claims description 2
- 235000011086 calcium lactate Nutrition 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 229960001714 calcium phosphate Drugs 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 229940088006 calcium pidolate Drugs 0.000 claims description 2
- FATUQANACHZLRT-XBQZYUPDSA-L calcium;(2r,3r,4s,5r,6r)-2,3,4,5,6,7-hexahydroxyheptanoate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C([O-])=O FATUQANACHZLRT-XBQZYUPDSA-L 0.000 claims description 2
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims description 2
- YQFZERWESBDNRJ-UHFFFAOYSA-L calcium;5-oxopyrrolidine-2-carboxylate Chemical compound [Ca+2].[O-]C(=O)C1CCC(=O)N1.[O-]C(=O)C1CCC(=O)N1 YQFZERWESBDNRJ-UHFFFAOYSA-L 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 239000010514 hydrogenated cottonseed oil Substances 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 2
- 229960001462 sodium cyclamate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- 235000013337 tricalcium citrate Nutrition 0.000 claims description 2
- 230000002195 synergetic effect Effects 0.000 abstract description 2
- 239000000843 powder Substances 0.000 description 11
- 229940088594 vitamin Drugs 0.000 description 11
- 229930003231 vitamin Natural products 0.000 description 11
- 235000013343 vitamin Nutrition 0.000 description 11
- 239000011782 vitamin Substances 0.000 description 11
- 150000003722 vitamin derivatives Chemical class 0.000 description 10
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical group OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 9
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000005979 Citrus limon Nutrition 0.000 description 3
- 244000131522 Citrus pyriformis Species 0.000 description 3
- 206010020100 Hip fracture Diseases 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 2
- 229910000394 calcium triphosphate Inorganic materials 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 231100000357 carcinogen Toxicity 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- -1 cholecalciferol-D3 vitamin Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000009481 moist granulation Methods 0.000 description 2
- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 1
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 244000024675 Eruca sativa Species 0.000 description 1
- 235000014755 Eruca sativa Nutrition 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 244000145845 chattering Species 0.000 description 1
- 229940090568 combinations of vitamin Drugs 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002706 dry binder Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
Foreliggende oppfinnelse vedrører en ny terapeutisk kombinasjon av vitamin og The present invention relates to a new therapeutic combination of vitamin and
kalsium. calcium.
Tallrike kombinasjoner av vitamin og kalsium er kjent for behandling av diverse Numerous combinations of vitamin and calcium are known for the treatment of various
sykdommer. diseases.
De terapeutiske effekter som er assosiert med samtidig administrering av kalsium og av vitamin D er velkjente, som f .eks. beskrevet i artikler av Marie C. Chapuy et al. "Ef-fekt av kalsium og cholecalciferol-behandling i tre år på hoftefrakturer hos eldre kvinner", British Medical Journal, 308, s. 1081-1082 (23. april 1994); Marie C. Chapuy et al. The therapeutic effects associated with the simultaneous administration of calcium and vitamin D are well known, as e.g. described in articles by Marie C. Chapuy et al. "Effect of Calcium and Cholecalciferol Treatment for Three Years on Hip Fractures in Elderly Women", British Medical Journal, 308, pp. 1081-1082 (April 23, 1994); Marie C. Chapuy et al.
"Vitamin D3 og kalsium for å forhindre hoftebrudd hos eldre kvinner", New England Journal of Medicine, 337, s. 1637-1642 (3. desember 1992); og i artikkelen med tittelen "Supplering med vitamin D3 og kalsium forhindrer hoftebrudd hos eldre kvinner", Nut-rition Reviews, vol. 51, 6, s. 183-185. "Vitamin D3 and Calcium to Prevent Hip Fractures in Older Women", New England Journal of Medicine, 337, pp. 1637-1642 (December 3, 1992); and in the article entitled "Vitamin D3 and Calcium Supplementation Prevents Hip Fractures in Older Women", Nut-rition Reviews, vol. 51, 6, pp. 183-185.
Disse artikler viser også variabiliteten av de terapeutiske effekter ved kombinasjonen som en funksjon av kalsiumdosering og av vitamin D-dosering, med en These articles also show the variability of the therapeutic effects of the combination as a function of calcium dosage and of vitamin D dosage, with a
optimal daglig dose som ligger rundt 1000 mg til 1200 mg av elementært kalsium og 800 IU av vitamin D3 for formålet med å forhindre og behandle osteoporose. optimal daily dose which is around 1000 mg to 1200 mg of elemental calcium and 800 IU of vitamin D3 for the purpose of preventing and treating osteoporosis.
Kalsium og vitamin D blir generelt administrert samtidig til pasienten, men i Calcium and vitamin D are generally administered at the same time to the patient, but i
separate former, f.eks. tabletter av et kalsiumsalt og dråper av vitamin D. separate forms, e.g. tablets of a calcium salt and drops of vitamin D.
Både vitamin D og saltene av kalsium som er akseptable ut fra det farmakologiske synspunkt oppviser karakteristikker som er sterkt spesifikke fra det galeniske synspunkt (se spesielt EP-A-O- 413 828 som vedrører et stabilisert preparat av vitamin D3 for potensialisering av stabiliteten av den aktive ingrediens), som fører til at de blir pakket i separate former. Both vitamin D and the salts of calcium which are acceptable from the pharmacological point of view exhibit characteristics that are highly specific from the galenic point of view (see in particular EP-A-O-413 828 which relates to a stabilized preparation of vitamin D3 for potentiating the stability of the active ingredient ), which causes them to be packaged in separate forms.
Imidlertid gjør det det vanskelig å sikre at absolutte og relative doseringer av kalsium og av vitamin D oppfylles, og således at behandlingen utføres korrekt, spesielt hvis den finner sted over et langt tidsrom. However, it makes it difficult to ensure that absolute and relative dosages of calcium and of vitamin D are met, and thus that the treatment is carried out correctly, especially if it takes place over a long period of time.
Det er allerede blitt fremsatt forslag for å assosiere kalsium og vitamin D i samme form, f.eks. i WO-A-94 06435 (en gynekologisk behandlingsmetode som spesielt anvender en kombinasjon av vitamin D og kalsium), i WO-A-92 19251 (en kombinasjon av vitamin D med kalsium for behandling av osteoporose, spesielt i form av en drikk), i EP-A-O-197 514 (et farmasøytisk preparat som omfatter et parathyroidhormon eller et fysiologisk aktivt fragment derav i kombinasjon med hydroksylert vitamin D eller et ikke-toksisk kalsrumsalt for økning av ben masse), eller faktisk i DE-A-42 12 122 (et lavkalori-element basert på proteiner, et kalsiumsalt og vitamin D). Proposals have already been made to associate calcium and vitamin D in the same form, e.g. in WO-A-94 06435 (a gynecological treatment method using in particular a combination of vitamin D and calcium), in WO-A-92 19251 (a combination of vitamin D with calcium for the treatment of osteoporosis, in particular in the form of a drink) , in EP-A-O-197 514 (a pharmaceutical preparation comprising a parathyroid hormone or a physiologically active fragment thereof in combination with hydroxylated vitamin D or a non-toxic calcium salt for increasing bone mass), or indeed in DE-A-42 12 122 (a low-calorie element based on proteins, a calcium salt and vitamin D).
Imidlertid er andelene av kalsium og av vitamin D i disse kjente former vanligvis langt fra de ønskelige optimale andeler som er antydet spesielt i den ovenfor spesifiserte litteratur. However, the proportions of calcium and of vitamin D in these known forms are usually far from the desirable optimum proportions which are indicated especially in the literature specified above.
Disse kjente former tilsvarer også ofte mer vitamin og kalsiumsupplement {matvaresupplement eller "OTC"-spesialiteter som selges uten resept) enn reelle farmasøytiske spesialiteter for terapeutiske formål ment for å forhindre eller behandle slike sykdommer som osteoporose med nøyaktig dosering. Also, these known forms often correspond more to vitamin and calcium supplements (dietary supplements or "OTC" specialties sold without a prescription) than real pharmaceutical specialties for therapeutic purposes intended to prevent or treat such diseases as osteoporosis with precise dosage.
For tiden eksisterer det et behov for å være i stand til å råde over en kombinasjon av vitamin og av kalsium inklusive i en eneste form en optimal relativ dose av kalsium og av vitamin D, mest spesielt for å forhindre og behandle osteoporose. Currently, there exists a need to be able to provide a combination of vitamin and calcium including in a single form an optimal relative dose of calcium and vitamin D, most especially for preventing and treating osteoporosis.
Imidlertid, på grunn av naturen av de tilgjengelige kalsiumsalter som er akseptable ut fra et farmasøytisk synspunkt, er det relativt vanskelig å assosiere kalsium i elementær form med vitamin D i visse spesifikke doseringer. Dette er spesielt tilfelle hvis det ønskes å oppnå tabletter ved en direkte kompresjonsproduksjonsmetode. De restriksjoner som ligger på de aktive ingredienser, spesielt kalsiumet i elementær form og formen av vitamin D, forhindrer da direkte å ta dette i bruk. However, due to the nature of the available calcium salts which are acceptable from a pharmaceutical point of view, it is relatively difficult to associate calcium in elemental form with vitamin D in certain specific dosages. This is particularly the case if it is desired to obtain tablets by a direct compression production method. The restrictions on the active ingredients, especially calcium in elemental form and the form of vitamin D, then directly prevent this from being used.
Foreliggende oppfinnelse løser de ovennevnte problemer ved å foreslå en terapeutisk kombinasjon i galenisk enhetstablettform for biting, som omfatter som assosierte aktive ingredienser: The present invention solves the above-mentioned problems by proposing a therapeutic combination in galenic unit tablet form for biting, which comprises as associated active ingredients:
- kalsium - calcium
- minst ett vitamin D, - at least one vitamin D,
idet forholdet mellom kalsium og vitamin D, uttrykt i mg av elementært Ca pr. since the ratio between calcium and vitamin D, expressed in mg of elemental Ca per
IU av vitamin D, ligger i området 1 til 1,5, og ytterligere inkluderer: IU of vitamin D, ranges from 1 to 1.5, and further includes:
-minst ett første tørt og fuktig bindemiddel kombinert med -at least one first dry and moist binder combined with
- minst ett fortynningsmiddel, - at least one diluent,
- minst ett andre bindemiddel og - at least one other binder and
- minst ett smøremiddel, - at least one lubricant,
idet minst ett av nevnte fortynningsmiddel og bindemiddel er et søtningsmiddel av polyol type, idet nevnte fortynningsmiddel er xylitol. wherein at least one of said diluent and binder is a polyol-type sweetener, wherein said diluent is xylitol.
Oppfinnelsen vedrører også de følgende karakteristikker: The invention also relates to the following characteristics:
- forholdet mellom kalsium i elementær form og vitamin D, uttrykt i mg av elementært Ca pr. IU av vitamin D, ligger i området 1 til 1,5, fortrinnsvis i området 1,2 til 1,3; - kalsiumet i elementær form kommer fra et kalsiumsalt valgt blant kalsiumkarbonat, kalsiumpidolat, kalsiumlaktat, kalsiumcitrat, kalsiumglukonat, kalsiumklorid, kalsiumgluko-heptonat, kalsiumglycerofosfat og kalsiumfosfat; - vitamin D er valgt fra vitamin D2 eller ergocalciferol, vitamin D3 eller cholecalciferol, eller en blanding derav; • det andre søtende bindemiddel er sorbitol; - det tørre og fuktige bindemiddel er valgt blant cellulose, maltodekstrin og polyvinylpy rrolidon; - smøremidlet er valgt blant magnesiumstearat, stearinsyre, hydrogenen ricinusolje, hydrogenen bomullsolje og glycerol-behenat; kombinasjonen inkluderer også et aromamiddel og/eller et surgjørende middel og/eller et ytterligere søtningsmiddel valgt blant natriumsakkarinat, natriumcyklamat og aspartam; og • kombinasjonen av vitamin og kalsium tilsvarer følgende generelle resept: - the ratio between calcium in elemental form and vitamin D, expressed in mg of elemental Ca per IU of vitamin D is in the range 1 to 1.5, preferably in the range 1.2 to 1.3; - the calcium in elemental form comes from a calcium salt selected from calcium carbonate, calcium pidolate, calcium lactate, calcium citrate, calcium gluconate, calcium chloride, calcium glucoheptonate, calcium glycerophosphate and calcium phosphate; - vitamin D is selected from vitamin D2 or ergocalciferol, vitamin D3 or cholecalciferol, or a mixture thereof; • the second sweetening binder is sorbitol; - the dry and moist binder is selected from cellulose, maltodextrin and polyvinylpyrrolidone; - the lubricant is selected from magnesium stearate, stearic acid, hydrogenated castor oil, hydrogenated cottonseed oil and glycerol behenate; the combination also includes a flavoring agent and/or an acidifying agent and/or an additional sweetener selected from sodium saccharinate, sodium cyclamate and aspartame; and • the combination of vitamin and calcium corresponds to the following general prescription:
Diverse karakteristikker og fordeler ved foreliggende oppfinnelse fremgår av et eksempel nedenunder. Various characteristics and advantages of the present invention can be seen from an example below.
I dette eksempel er kombinasjonen i henhold til oppfinnelsen i form av en tablett som kan bites, som har følgende sammensetning (for en endelig tablett som veier 2500 mg): In this example, the combination according to the invention is in the form of a tablet that can be bitten, which has the following composition (for a final tablet weighing 2500 mg):
Kalsiumkarbonatet er av typen SCORALITE 1B<®> fra SCORA; det er i form av et hvitt pulver med svært fine kom, med en middeldiameter på ca. 12 pm og med høy densitet (d = 1,3 g/cm<3> omtrent) som strømmer dårlig og som er relativt uegnet for komprimering. The calcium carbonate is of the type SCORALITE 1B<®> from SCORA; it is in the form of a white powder with very fine grains, with a mean diameter of approx. 12 pm and with a high density (d = 1.3 g/cm<3> approximately) which flows poorly and which is relatively unsuitable for compaction.
Vitamin D er cholecalciferol (type 100 CWS®, fra ROCHE); det er i form av et granulert pulver med en middeldiameter på ca. 200 pm, det er gulaktig av farve og doseres med 100.000 IU pr. gram. Vitamin D is cholecalciferol (type 100 CWS®, from ROCHE); it is in the form of a granulated powder with a mean diameter of approx. 200 pm, it is yellowish in color and is dosed with 100,000 IU per gram.
Nærvær av DL-a-tokoferol (ca. 0,2 vekt% av vitamin E) gir en høy grad av stabilitet og forhindrer produktet fra å oksidere. The presence of DL-α-tocopherol (approx. 0.2% by weight of vitamin E) provides a high degree of stability and prevents the product from oxidizing.
Søtnings- og fortynningsmidlet som anvendes i forbindelse med oppfinnelsen, er fortrinnsvis xylitol av typen XYLITAB 300® fra FINNSUGAR. Slik xylitol er en polyol som smaker søtt (ekvivalent med sukrose som gir en behagelig følelse av friskhet i munnen, den er ikke et karsinogen og medfører svært få kalorier (2,4 Kcal/g sammenlignet med 4 Kcal/g for sukrose). Den behagelige følelse sikrer at behandlingen er bedre for pasienten. Den anvendte xylitol har komprimerbarhetsegenskaper som er bedre enn hva standard-xylitol har. The sweetener and diluent used in connection with the invention is preferably xylitol of the type XYLITAB 300® from FINNSUGAR. Such xylitol is a sweet-tasting polyol (equivalent to sucrose that gives a pleasant sensation of freshness in the mouth, it is not a carcinogen and carries very few calories (2.4 Kcal/g compared to 4 Kcal/g for sucrose). pleasant feeling ensures that the treatment is better for the patient.The xylitol used has compressibility properties that are better than what standard xylitol has.
Tabletten er i form av et hvitt krystallinsk granulert pulver med en middeldiameter på 250 pm. The tablet is in the form of a white crystalline granular powder with a mean diameter of 250 µm.
Søtningsmidlet og bindemidlet som anvendes i forbindelse med oppfinnelsen er spesielt sorbitol (av typen NEOSORB P 60 W®, fra ROQUETTE). Denne polyol er i form av et hvitt granulert pulver som har en middeldiameter på 200 um og har utmerkede binde-og kompresjonsegenskaper. Sorbitol har søt smak (70% av hva sukrose har), den er ikke et karsinogen og medfører få kalorier (2,4 Kcal/g). The sweetener and binder used in connection with the invention is in particular sorbitol (of the type NEOSORB P 60 W®, from ROQUETTE). This polyol is in the form of a white granular powder having an average diameter of 200 µm and has excellent binding and compression properties. Sorbitol has a sweet taste (70% of what sucrose has), it is not a carcinogen and contains few calories (2.4 Kcal/g).
Bindemidlet i henhold til oppfinnelsen er fortrinnsvis polyvinylpyrrolidon (av typen KOLLI DON K 30®, fra BASF); det er i form av et granulert, hvitaktig pulver og har svært store bindingsegenskaper i fuktige korn. Verdien av konstanten K karakteriserer løselige polyvinylpyrrolidoner og er avhengig av deres relative løselighet. The binder according to the invention is preferably polyvinylpyrrolidone (of the KOLLI DON K 30® type, from BASF); it is in the form of a granular, whitish powder and has very high binding properties in moist grains. The value of the constant K characterizes soluble polyvinylpyrrolidones and is dependent on their relative solubility.
Smaksmidlet er spesielt sitronsmak (SBI); det er i form av en fint, gulaktig pulver laget av essensielle oljer atomisert på martodekstrin. Tallrike tester som er utført med hensyn til å iverksette foreliggende oppfinnelse og å sammenligne forskjellige aromaer har vist at sitronaroma er helt ut egnet for å maskere den kalkaktige smak av kalsiumkarbonat og at den assosierer behagelig med følelsen av friskhet som xylitolen medfører. The flavoring agent is specifically lemon flavor (SBI); it is in the form of a fine, yellowish powder made from essential oils atomized on martodextrin. Numerous tests carried out with regard to implementing the present invention and comparing different aromas have shown that lemon aroma is perfectly suitable for masking the chalky taste of calcium carbonate and that it associates pleasantly with the feeling of freshness that xylitol brings.
Smøremidlet er generelt et magnesiumstearat i form av et hvitaktig, fint pulver som tjener til å unngå fenomenet hvorved matrisene til tablettfremstillingspressene klabber når vitamin/ kalsium-kombinasjonen i henhold til oppfinnelsen tilveiebringes i The lubricant is generally a magnesium stearate in the form of a whitish, fine powder which serves to avoid the phenomenon whereby the matrices of the tablet-making presses clatter when the vitamin/calcium combination according to the invention is provided in
tablettform. tablet form.
Mengden av elementært kalsium pr. dose er fortrinnsvis 500 mg, hvilket tilsvarer The amount of elemental calcium per dose is preferably 500 mg, which corresponds to
1250 mg kalsiumkarbonat. 1250 mg calcium carbonate.
Mengden av cholicalciferol pr. dose er 4 mg, hvilket tilsvarer 400 IU av vitamin D3 med 100.0001U/g. I praksis avhenger mengden av cholecalciferol, pr. tablett av doseringen av det anvendte råmateriale. The amount of cholicalciferol per dose is 4 mg, which corresponds to 400 IU of vitamin D3 with 100.0001U/g. In practice, the amount of cholecalciferol depends, per tablet of the dosage of the raw material used.
Disse doser tilsvarer spesielt optimal dosering som gitt i de ovennevnte publikasjoner, både med hensyn til absolutt verdi (daglige doser av henholdsvis kalsium og av vitamin D3) og relative doser (forhold mellom kalsium og vitamin på ca. 1,25 mg av elementært Ca pr. IU av vitamin D). These doses correspond in particular to optimal dosage as given in the above-mentioned publications, both with regard to absolute value (daily doses of calcium and vitamin D3 respectively) and relative doses (ratio between calcium and vitamin of approx. 1.25 mg of elemental Ca per .IU of vitamin D).
Tallrike tester angående blandinger i henhold til dette eksempel har muliggjort Numerous tests regarding mixtures according to this example have made possible
optimalisering av mengdene av de forskjellige eksipienter. optimization of the amounts of the different excipients.
For å oppnå en tablett som kan bites, som har den mest mulig behagelige smak, må bidraget av tørt bindemiddel og av fuktig miljø kombinert i synergistisk mengde med minst det søtende fortynningsmiddel, minst det søtende bindemiddel og minst smøremidlet, være betydelig. For en tablett betyr dette at dens vekt generelt vil være 2500 mg. In order to obtain a bitetable tablet having the most pleasant taste possible, the contribution of dry binder and of moist environment combined in a synergistic amount with at least the sweetening diluent, at least the sweetening binder and at least the lubricant must be significant. For a tablet, this means that its weight will generally be 2500 mg.
I visse utføre Ise sf orme r av foreliggende oppfinnelse er mengden av xylitol som anvendes ca. 661 mg, som tilsvarer den mengde som trenges å bli inkorporert for oppnåelse av den beste maskering av kalsiumkarbonatsmaken uten samtidig å redusere komprimerbarheten av blandingen, forutsatt at kompresjonsegenskapene til xylitol er gjennomsnittlige. In certain embodiments of the present invention, the amount of xylitol used is approx. 661 mg, which corresponds to the amount that needs to be incorporated to achieve the best masking of the calcium carbonate taste without at the same time reducing the compressibility of the mixture, provided that the compression properties of xylitol are average.
Sorbitolen anvendes med ca. 500 mg, siden det er den mengde som trenges å bli inkorporert for at man skal oppnå god reproduserbarhet av brekkestyrkeområdet, en parameter som er kritisk for tabletter som skal bites. En høyere mengde, på bekostning av xylitol, ville redusere smakskvaliteten til tabletten. The sorbitol is used with approx. 500 mg, since that is the amount that needs to be incorporated in order to achieve good reproducibility of the breaking strength range, a parameter that is critical for tablets to be bitten. A higher amount, at the expense of xylitol, would reduce the taste quality of the tablet.
Polyvinylpyrrolidonet anvendes i en rate på ca. 45 mg under fuktig granulering av kalsiumkarbonatet, idet en porsjon (20 mg) blir blandet tørt med kalsiumkarbonatet mens resten (25 mg) anvendes i en løsning med 10% i kaldt demineralisert vann. Ét polyvinyl-pyrrolidoninnhold på mindre enn 40 mg fører til at kornene av kalsiumkarbonat blir svært sprø. En større mengde gir ikke noen virkelig nytte. The polyvinylpyrrolidone is used at a rate of approx. 45 mg during moist granulation of the calcium carbonate, with a portion (20 mg) being mixed dry with the calcium carbonate while the rest (25 mg) is used in a solution with 10% in cold demineralized water. A polyvinyl pyrrolidone content of less than 40 mg causes the grains of calcium carbonate to become very brittle. A larger amount does not provide any real benefit.
Mengden av sitronaroma er ca. 20 mg, og dette er den mengde som kreves for å gi tilfredsstillende aroma til tabletten. Små variasjoner i denne mengde (±3 mg) foranlediger praktisk talt ingen endring i den endelige smak. The amount of lemon flavor is approx. 20 mg, and this is the amount required to give a satisfactory aroma to the tablet. Small variations in this amount (±3 mg) cause practically no change in the final taste.
Mengden av magnesiumstearat er ca. 20 mg. Dette er den mengde som kreves for å oppnå tilfredsstillende smøring under komprimering. En mindre mengde, ca. 15 mg, ville foranledige et klabbefenomen, mens en større mengde, 25 mg, ville ha tendens til å redusere hardheten til tabletten og løpe risikoen for å endre dens smak. The amount of magnesium stearate is approx. 20 mg. This is the amount required to achieve satisfactory lubrication during compression. A smaller amount, approx. 15 mg, would cause a chattering phenomenon, while a larger amount, 25 mg, would tend to reduce the hardness of the tablet and run the risk of changing its taste.
De fysiske karakteristikker hos elementene som til sammen utgjør kombinasjonen The physical characteristics of the elements that together make up the combination
av vitamin og kalsium i henhold til foreliggende oppfinnelse er beskrevet nedenunder. of vitamin and calcium according to the present invention is described below.
Kalsiumkarbonat har null flyt, og dets tilsynelatende densitet (g/cm3) er ca. 1,28-1,35 for et restfuktighetsinnhold på 0,1%. Cholecalciferol-D3-vitaminet i form av et konsentrat i pulverform har en flyt på 6 sek. for 100 g pulver, en tilsynelatende densitet på 0,73 g/cm<3>, et restfuktighetsinnhold på 6,4% og en dosering i IU/g på 100.000. Calcium carbonate has zero flow, and its apparent density (g/cm3) is approx. 1.28-1.35 for a residual moisture content of 0.1%. The cholecalciferol-D3 vitamin in the form of a concentrate in powder form has a flow of 6 seconds. for 100 g of powder, an apparent density of 0.73 g/cm<3>, a residual moisture content of 6.4% and a dosage in IU/g of 100,000.
Xylitolen har null flyt og tilsynelatende densitet på ca. 0,68 g/cm<3> 0,69 g/cm<3>, og resterende fuktighetsinnhold på Xylitol has zero flow and an apparent density of approx. 0.68 g/cm<3> 0.69 g/cm<3>, and residual moisture content of
0,2-0,3%. 0.2-0.3%.
Sorbitol har flytverdier i området 4-5 sek. for 100 g pulver, en tilsynelatende densitet på 0,71 g/cm<3> - 0,73 g/cm3 og et resterende fuktighetsinnhold på 0,5%-0,8%. Sorbitol has flow values in the range of 4-5 sec. for 100 g of powder, an apparent density of 0.71 g/cm<3> - 0.73 g/cm3 and a residual moisture content of 0.5%-0.8%.
De foretrukne trinn ved utførelse av fremgangsmåten med å oppnå kombinasjonen av vitamin og kalsium i henhold til foreliggende oppfinnelse er beskrevet nedenunder. The preferred steps in carrying out the method of obtaining the combination of vitamin and calcium according to the present invention are described below.
Innledningsvis utføres fuktig granulering av kalsiumkarbonatet. Initially, moist granulation of the calcium carbonate is carried out.
I denne utførelsesform blir kalsiumkarbonatet og polyvinylpyrrolidonet siktet gjennom en vibrerende sikt forsynt med en duk som har en riktig maskestørrelse; disse pulvere blir brakt inn i en mikser, og de mikses sammen i et kort tidsrom ved en passende hastighet. Polyvinylpyrrolidonløsning blir tilsatt i suksessive trinn. Granulering blir utført inntil en fuktig masse blir oppnådd, hvilket gjør det mulig å foreta et følgende prekalibreringstrinn. In this embodiment, the calcium carbonate and polyvinylpyrrolidone are sieved through a vibrating sieve provided with a cloth having a proper mesh size; these powders are brought into a mixer and they are mixed together for a short period of time at an appropriate speed. Polyvinylpyrrolidone solution is added in successive steps. Granulation is carried out until a moist mass is obtained, which makes it possible to carry out a following precalibration step.
Prekalibrering blir utført på en granulator forsynt med en duk som har en passende maskestørrelse. Precalibration is carried out on a granulator equipped with a screen that has an appropriate mesh size.
Det resulterende produkt blir tørket på et fluidisert luftsjikt og får avkjøle seg. The resulting product is dried on a fluidized air bed and allowed to cool.
Vekttapet ved tørking blir bestemt, og kalibrering på en duk med passende maskestørrelse blir utført. The weight loss on drying is determined, and calibration on a cloth with the appropriate mesh size is performed.
Parallelt premikses vitamin D3, og etter sikting blir det mikset med sorbitol i en mikser i et passende langt tidsrom ved en passende rotasjonshastighet. Deretter mikses de andre ingredienser inn, xylitolen siktes, sorbitolen og aromastoffet siktes over en vibrerende sikt tilpasset med en duk som har en passende maskestørrelse. Disse tre ingredienser blir mikset med forhåndsblandingen av vitamin D3 og sorbitol i en mikser ved en passende hastighet. Deretter blir det granulerte kalsiumkarbonat innført, og miksingen fortsetter i det nødvendige tidsrom ved den aktuelle hastighet. In parallel, vitamin D3 is premixed, and after sieving it is mixed with sorbitol in a mixer for a suitable length of time at a suitable rotational speed. The other ingredients are then mixed in, the xylitol is sieved, the sorbitol and the flavoring substance is sieved over a vibrating sieve fitted with a cloth that has a suitable mesh size. These three ingredients are mixed with the premix of vitamin D3 and sorbitol in a mixer at an appropriate speed. Then the granulated calcium carbonate is introduced, and mixing continues for the required time at the appropriate speed.
Magnesiumstearatet blir siktet på en vibrerende sikt forsynt med en duk som har en passende maskestørrelse, og deretter blir hele blandingen mikset i en mikser. The magnesium stearate is sieved on a vibrating sieve fitted with a cloth having a suitable mesh size, and then the whole mixture is mixed in a mixer.
Den ovenfor beskrevne blanding blir så komprimert i en presse under régelmessig overvåkning av vektens jevnhet og bruddstyrke. De tider som kreves for miksing, rotasjonshastighetene og maskestørrelsene til siktene er konvensjonelle og velkjente for fagmannen på området. The mixture described above is then compressed in a press under regular monitoring of the evenness of the weight and breaking strength. The times required for mixing, the rotational speeds and the mesh sizes of the sieves are conventional and well known to those skilled in the art.
Foreliggende oppfinnelse gjør det derfor mulig å oppnå en kombinasjon av vitamin og kalsium som inneholder 500 mg elementært kalsium og 4 mg vitamin D3 pr. dose, og denne kombinasjon er spesifikt i form av en tablett for biting som har behagelig smak og har en hardhet som er tilpasset pasientene. The present invention therefore makes it possible to obtain a combination of vitamin and calcium containing 500 mg of elemental calcium and 4 mg of vitamin D3 per dose, and this combination is specifically in the form of a tablet for biting which has a pleasant taste and has a hardness adapted to the patients.
Mer spesielt, ved hjelp av et ikke-begrensende eksempel, vil doser generelt bli anvendt i de følgende områder: kalsium i elementær form ca. 500 mg til ca. 1500 mg; vitamin D eller en blanding av vitaminer D, ca. 3,5 mg til ca. 12 mg. En slik kombinasjon av vitamin og kalsium, spesielt i tablettform, inneholder verken sukker eller natrium. More specifically, by way of non-limiting example, doses will generally be used in the following ranges: calcium in elemental form approx. 500 mg to approx. 1500 mg; vitamin D or a mixture of vitamins D, approx. 3.5 mg to approx. 12 mg. Such a combination of vitamin and calcium, especially in tablet form, contains neither sugar nor sodium.
Imidlertid er det mulig med andre galeniske former. However, other galenic forms are possible.
Det er således mulig å tilveiebringe en splittbar tablett (for svelging) som har It is thus possible to provide a splittable tablet (for swallowing) which has
følgende sammensetning for en 1,60 g tablett: the following composition for a 1.60 g tablet:
Generelt anvendes kalsiumkarbonat for å tilveiebringe tabletter av en type som kan tygges. Andre salter, f.eks. kalsiumtrifosfat, kunne anvendes, men de absorberes mindre godt av legemet, hvilket betyr at mengdene ville måtte tilpasses forholdsmessig (for et gitt kvantum av absorbert elementært kalsium er det nødvendig å anvende ca. 1,2 g kalsiumtrifosfat for 1 g kalsiumkarbonat). Generally, calcium carbonate is used to provide tablets of a chewable type. Other salts, e.g. calcium triphosphate, could be used, but they are absorbed less well by the body, which means that the quantities would have to be adapted proportionately (for a given quantity of absorbed elemental calcium, it is necessary to use approx. 1.2 g of calcium triphosphate for 1 g of calcium carbonate).
Claims (11)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9411381A FR2724844B1 (en) | 1994-09-23 | 1994-09-23 | VITAMIN-CALCIUM THERAPEUTIC COMBINATION, PROCESS FOR OBTAINING SAME AND USE THEREOF |
| PCT/FR1995/001053 WO1996009036A1 (en) | 1994-09-23 | 1995-08-04 | Therapeutic vitamin-calcium combination in unitary galenic tablet form, method for preparing same and use thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO971356D0 NO971356D0 (en) | 1997-03-21 |
| NO971356L NO971356L (en) | 1997-03-21 |
| NO323814B1 true NO323814B1 (en) | 2007-07-09 |
Family
ID=9467219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19971356A NO323814B1 (en) | 1994-09-23 | 1997-03-21 | Therapeutic combination in galenic unit tablet form. |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0785769B1 (en) |
| JP (1) | JPH10505850A (en) |
| KR (1) | KR100373393B1 (en) |
| AT (1) | ATE177319T1 (en) |
| AU (1) | AU3168395A (en) |
| CA (1) | CA2200568C (en) |
| DE (1) | DE69508263T2 (en) |
| DK (1) | DK0785769T3 (en) |
| ES (1) | ES2131845T3 (en) |
| FI (1) | FI971188A (en) |
| FR (1) | FR2724844B1 (en) |
| GR (1) | GR3030266T3 (en) |
| HU (1) | HU219597B (en) |
| NO (1) | NO323814B1 (en) |
| OA (1) | OA10336A (en) |
| PL (1) | PL181340B1 (en) |
| RU (1) | RU2154466C2 (en) |
| WO (1) | WO1996009036A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO331462B1 (en) * | 1998-11-13 | 2012-01-09 | Nycomed Pharma As | Process for the preparation of an orally administrable calcium composition in tablet form |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6716454B2 (en) | 1994-09-23 | 2004-04-06 | Laboratorie Innothera, Société Anonyme | Therapeutic combination of vitamin and calcium in unitary galenic tablet form, a method of obtaining it, and the use thereof |
| DE19639343C2 (en) | 1996-09-25 | 1998-10-08 | Suedzucker Ag | Comprimate containing a sweetener mixture |
| DE19710054A1 (en) * | 1997-03-12 | 1998-09-17 | Merck Patent Gmbh | Pharmaceutical preparation |
| FR2760639B1 (en) * | 1997-03-14 | 2000-09-22 | Innothera Lab Sa | MINERALO-VITAMIN THERAPEUTIC ASSOCIATION IN THE FORM OF A UNITABLE ORAL LIQUID PREPARATION |
| FR2762217B1 (en) * | 1997-04-16 | 2000-09-29 | Besins Iscovesco Lab | SOLID VITAMINO-CALCIUM PREPARATION, PROCESS FOR OBTAINING SAME AND USE THEREOF |
| FR2765804B1 (en) * | 1997-07-09 | 2003-10-10 | Inst Pharma De Rech Applic Et | CALCIUM-PROVIDING PHARMACEUTICAL COMPOSITION AND ORAL GALENIC FORMS COMPRISING SUCH A COMPOSITION |
| ITFI970184A1 (en) * | 1997-07-30 | 1999-01-30 | Menarini Farma Ind | PHARMACEUTICAL COMPOSITIONS CONTAINING VITAMIN D AND CALCIUM, THEIR PREPARATION AND THERAPEUTIC USE |
| CN1067250C (en) * | 1997-08-21 | 2001-06-20 | 中国人民解放军总装备部后勤部军事医学研究所 | Series product of high-effective neutral calcium-supplementary preparation |
| FR2780861B1 (en) * | 1998-07-08 | 2000-09-08 | Remy Laurenceau | COMPOSITION FOR LAYING POULTRY CONTAINING CALCIUM L-PIDOLATE |
| RU2195269C2 (en) * | 2001-02-14 | 2002-12-27 | Общество с ограниченной ответственностью "МДТ" | Vitamin-mineral complex |
| DE10317922B4 (en) * | 2003-04-17 | 2009-11-26 | Presearch Gmbh | Use of a combination preparation of oral contraceptive and calcium / vitamin D. |
| KR100898970B1 (en) | 2004-05-24 | 2009-05-25 | 니코메드 파마 에이에스 | Particulate comprising a calcium-containing compound and a sugar alcohol |
| CN1997362B (en) * | 2004-06-01 | 2010-09-08 | 奈科明制药有限公司 | Chewable, suckable and swallowable tablet containing a caicium-containing compound as an active substance |
| WO2006046111A1 (en) * | 2004-10-26 | 2006-05-04 | Nycomed Pharma As | Use of xylitol as an anti-chalk acting agent in compositions for oral use containing a calcium-containing compound as an active substance |
| CN103479582A (en) | 2005-02-03 | 2014-01-01 | 武田奈科明有限公司 | Fast wet-massing method for the preparation of calcium-containing compositions |
| EP1845949B1 (en) | 2005-02-03 | 2008-05-21 | Nycomed Pharma AS | Melt granulation of a composition containing a calcium-containing compound |
| PL1861073T5 (en) * | 2005-03-04 | 2012-09-28 | Takeda As | Process for the production of calcium compositions in a continuous fluid bed |
| UA95093C2 (en) | 2005-12-07 | 2011-07-11 | Нікомед Фарма Ас | Method for the preparation of calcium-containing compound |
| CN101365426B (en) | 2005-12-07 | 2012-08-08 | 奈科明制药有限公司 | Pre-compacted calcium-containing compositions |
| KR100825572B1 (en) | 2006-08-30 | 2008-04-25 | 일양약품주식회사 | Liquid Formulation Containing Calcium, Magnesium and Vitamin, and Preparing Method Thereof |
| GB0818473D0 (en) | 2008-10-08 | 2008-11-12 | Probio Nutraceuticals As | Composition |
| MX2011004744A (en) | 2008-11-17 | 2011-05-30 | Nycomed Pharma As | Improved dissolution stability of calcium carbonate tablets. |
| CN107281216B (en) * | 2017-06-16 | 2020-05-05 | 北京济美堂医药研究有限公司 | Pharmaceutical preparation containing calcium compound |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2525478B2 (en) * | 1989-03-01 | 1996-08-21 | 帝人株式会社 | Active Vitamin D with improved stability (3) Lower solid preparation |
-
1994
- 1994-09-23 FR FR9411381A patent/FR2724844B1/en not_active Expired - Fee Related
-
1995
- 1995-08-04 WO PCT/FR1995/001053 patent/WO1996009036A1/en not_active Application Discontinuation
- 1995-08-04 KR KR1019970701730A patent/KR100373393B1/en not_active IP Right Cessation
- 1995-08-04 AU AU31683/95A patent/AU3168395A/en not_active Abandoned
- 1995-08-04 CA CA002200568A patent/CA2200568C/en not_active Expired - Fee Related
- 1995-08-04 RU RU97106555/14A patent/RU2154466C2/en not_active IP Right Cessation
- 1995-08-04 HU HU9702099A patent/HU219597B/en not_active IP Right Cessation
- 1995-08-04 JP JP8510639A patent/JPH10505850A/en active Pending
- 1995-08-04 ES ES95927758T patent/ES2131845T3/en not_active Expired - Lifetime
- 1995-08-04 DK DK95927758T patent/DK0785769T3/en active
- 1995-08-04 EP EP95927758A patent/EP0785769B1/en not_active Revoked
- 1995-08-04 PL PL95319585A patent/PL181340B1/en not_active IP Right Cessation
- 1995-08-04 DE DE69508263T patent/DE69508263T2/en not_active Revoked
- 1995-08-04 AT AT95927758T patent/ATE177319T1/en not_active IP Right Cessation
-
1996
- 1996-11-01 OA OA60916A patent/OA10336A/en unknown
-
1997
- 1997-03-21 FI FI971188A patent/FI971188A/en not_active Application Discontinuation
- 1997-03-21 NO NO19971356A patent/NO323814B1/en not_active IP Right Cessation
-
1999
- 1999-05-19 GR GR990401359T patent/GR3030266T3/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO331462B1 (en) * | 1998-11-13 | 2012-01-09 | Nycomed Pharma As | Process for the preparation of an orally administrable calcium composition in tablet form |
Also Published As
| Publication number | Publication date |
|---|---|
| HU219597B (en) | 2001-05-28 |
| FR2724844A1 (en) | 1996-03-29 |
| RU2154466C2 (en) | 2000-08-20 |
| EP0785769A1 (en) | 1997-07-30 |
| NO971356D0 (en) | 1997-03-21 |
| WO1996009036A1 (en) | 1996-03-28 |
| KR100373393B1 (en) | 2003-05-16 |
| HUT77702A (en) | 1998-07-28 |
| DE69508263T2 (en) | 1999-11-04 |
| PL319585A1 (en) | 1997-08-18 |
| DE69508263D1 (en) | 1999-04-15 |
| FI971188A0 (en) | 1997-03-21 |
| AU3168395A (en) | 1996-04-09 |
| CA2200568C (en) | 2008-10-28 |
| ATE177319T1 (en) | 1999-03-15 |
| KR970705975A (en) | 1997-11-03 |
| PL181340B1 (en) | 2001-07-31 |
| GR3030266T3 (en) | 1999-08-31 |
| OA10336A (en) | 1997-10-07 |
| DK0785769T3 (en) | 1999-09-27 |
| NO971356L (en) | 1997-03-21 |
| EP0785769B1 (en) | 1999-03-10 |
| FI971188A (en) | 1997-05-20 |
| FR2724844B1 (en) | 1997-01-24 |
| ES2131845T3 (en) | 1999-08-01 |
| JPH10505850A (en) | 1998-06-09 |
| CA2200568A1 (en) | 1996-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO323814B1 (en) | Therapeutic combination in galenic unit tablet form. | |
| US6716454B2 (en) | Therapeutic combination of vitamin and calcium in unitary galenic tablet form, a method of obtaining it, and the use thereof | |
| EP1128815B1 (en) | Process for preparing oral calcium compositions | |
| KR100258223B1 (en) | Fast dissolving tablet and its production | |
| EP1837019B1 (en) | Orally-dispersible pharmaceutical compositions | |
| US5322694A (en) | Pharmaceutical lozenges | |
| CZ287378B6 (en) | Pharmaceutical preparation containing fluoxetine and process for preparing thereof | |
| KR20070116291A (en) | Rapidly disintegrating methylcellulose tablets | |
| KR101203186B1 (en) | Taste-masked pharmaceutical composition for oral administration and a process for the preparation thereof | |
| RU2174837C2 (en) | Rapidly decomposing ready preparative form of tramadol or tramadol salt | |
| RU2161033C2 (en) | Combined osmotic and volume-forming purgative agents | |
| EA015035B1 (en) | Pre-compacted calcium-containing compositions | |
| KR101175120B1 (en) | Nateglinide-containing preparation | |
| CN113365612A (en) | Method for producing easy-to-take tablet containing ginkgo leaf dry extract | |
| WO2010067151A1 (en) | Quick disintegrating taste masked composition | |
| RU2796676C1 (en) | Water-soluble tablets of colecalciferol and method for their production | |
| PL196058B1 (en) | Calcium lactate effervescent tablet and method for manufacture of calcium lactate effervescent tablets | |
| DE29521515U1 (en) | A therapeutic combination of vitamin and calcium in a uniform galenic tablet form | |
| CN104136033A (en) | Antacid tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |