EP0797444A1 - Trousse pour cycle de traitement de l'osteoporose - Google Patents
Trousse pour cycle de traitement de l'osteoporoseInfo
- Publication number
- EP0797444A1 EP0797444A1 EP95941761A EP95941761A EP0797444A1 EP 0797444 A1 EP0797444 A1 EP 0797444A1 EP 95941761 A EP95941761 A EP 95941761A EP 95941761 A EP95941761 A EP 95941761A EP 0797444 A1 EP0797444 A1 EP 0797444A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- tiludronic acid
- calcium
- pharmaceutically acceptable
- kit
- acceptable salts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 18
- 238000011282 treatment Methods 0.000 title claims abstract description 17
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims abstract description 42
- 229960005324 tiludronic acid Drugs 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 239000011575 calcium Substances 0.000 claims abstract description 26
- 239000012453 solvate Substances 0.000 claims abstract description 23
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 17
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 235000015872 dietary supplement Nutrition 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 14
- SKUHWSDHMJMHIW-UHFFFAOYSA-L disodium;[(4-chlorophenyl)sulfanyl-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate Chemical compound [Na+].[Na+].OP([O-])(=O)C(P(O)([O-])=O)SC1=CC=C(Cl)C=C1 SKUHWSDHMJMHIW-UHFFFAOYSA-L 0.000 claims description 9
- 239000013589 supplement Substances 0.000 claims description 8
- 230000000050 nutritive effect Effects 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 5
- -1 disodium tiludronate monohydrate Chemical class 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 235000005911 diet Nutrition 0.000 claims description 3
- 230000037213 diet Effects 0.000 claims description 3
- BWAUQTFFVCLSOS-UHFFFAOYSA-N sodiosodium hydrate Chemical compound O.[Na].[Na] BWAUQTFFVCLSOS-UHFFFAOYSA-N 0.000 claims description 2
- 150000004682 monohydrates Chemical class 0.000 claims 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 1
- 235000008935 nutritious Nutrition 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 8
- 239000003826 tablet Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229940122361 Bisphosphonate Drugs 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 150000004663 bisphosphonates Chemical class 0.000 description 5
- 159000000007 calcium salts Chemical class 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 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 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229960000913 crospovidone Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 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 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- PWKNEBQRTUXXLT-ZBHRUSISSA-L calcium lactate gluconate Chemical compound [Ca+2].CC(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O PWKNEBQRTUXXLT-ZBHRUSISSA-L 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068911 chloride hexahydrate Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- VOAPTKOANCCNFV-UHFFFAOYSA-N hexahydrate;hydrochloride Chemical compound O.O.O.O.O.O.Cl VOAPTKOANCCNFV-UHFFFAOYSA-N 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- CLJTZNIHUYFUMR-UHFFFAOYSA-M sodium;hydrogen carbonate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CLJTZNIHUYFUMR-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940019375 tiludronate Drugs 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 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
- A61K31/66—Phosphorus compounds
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a kit for use in a therapeutic cycle for the treatment and / or prevention of osteoporosis. More particularly, the invention relates to a kit for use in the therapy of osteoporosis where a bisphosphonate and a nutritional supplement (or a placebo) are administered sequentially.
- EP-A-0100718 describes new compounds having a structure
- bisphosphonate including (4-chlorophenyl) - tiomethylenediphosphonic acid, the corresponding INN of which is tiludronic acid. This compound has shown very interesting properties in the treatment of osteoporosis (J.Y. Reginster et al., The Lancet, Dec. 23/30, 1989).
- EP-A-0162510, BE 902308 and AU 8541619 describe sequential treatments for osteoporosis with kits containing a bone cell activator compound, a phosphonate and a nutritional supplement (or a placebo), to be administered in sequence, for periods defined times.
- EP-A-210728 describes a kit for use in the treatment of osteoporosis containing a bisphosphonate - to be administered for 1-90 days - and a nutritional supplement (or a placebo) - to be administered for the following 50-120 days.
- WO 94/00129 describes a method of treating osteoporosis comprising the administration of a "high potency" phosphonate in a treatment cycle of 1 to 30 days, optionally followed by a rest period of at least one day .
- the above international application lists "high potency” phosphonates which can be used according to the invention; in this patent application, tiludronate is indicated as one of the "low power” phosphonates, which are not suitable for carrying out the invention.
- the present invention therefore relates to a kit intended for the treatment and / or prevention of osteoporosis comprising the sequential administration of tiludronic acid or one of its salts and / or solvates and a nutritive supplement, said kit being characterized in that it contains:
- compositions of tiludronic acid include salts with physiologically compatible inorganic and organic bases; pharmaceutically acceptable salts of tiludronic acid are disodium tiludronate, disodium tiludronate hydrated and disodium tiludronate monohydrate (EP-582515), the latter two being preferred.
- the term "nutritional supplement in the present description indicates one or more substances which normally should be introduced into the organism by the regular food, like for example calcium and vitamin D; when these substances are not taken in sufficient quantity the normal diet runs the risk of jeopardizing the success of therapy with tiludronic acid or one of its salts and / or solvates, which is why therapy with tiludronic acid or one of its salts and / or solvates is associated with the administration of said nutritional supplement, a particularly advantageous nutritional supplement being calcium.
- the calcium is in salified form with pharmaceutically acceptable inorganic or organic acids.
- Such calcium salts include carbonate, chloride, chloride hexahydrate, citrate, formate, glucoheptonate, gluconate, gluconolactate, glutamate, glycerophosphate, hydrogenophosphate, lactate, lactobionate, lactophosphate, l ⁇ vulinate, oleate, monobasic or tribasic phosphate, pidolate, sulfate; gluconolactate, carbonate and gluconate are the particularly preferred calcium salts. Therefore, when talking about calcium, we are referring to a calcium salt in an amount corresponding to the desired dose of Ca ++ .
- the above calcium salts can be administered alone or in combination.
- the kit according to the invention allows the patient suffering from osteoporosis to carry out therapeutic cycles, based on the sequential administration of tiludronic acid or one of its salts and / or solvates and a nutritive supplement, convenient and safe way.
- the doses of tiludronic acid or one of its salts and / or solvates and nutritional supplement will be in the form of compositions intended for oral administration.
- said oral pharmaceutical compositions are solid forms, such as for example tablets, optionally scored, chewable or effervescent, capsules or granules.
- the main active ingredient tiludronic acid or one of its pharmaceutically acceptable salts and / or solvates
- a pharmaceutical vehicle such as gelatin, starch , lactose, magnesium stearate, talc, gum arabic, sodium lauryl sulfate, crospovidone, cellulose derivatives or the like.
- the tablets can be coated with sucrose or other suitable materials, for example for coloring, or they can be treated so that they have a prolonged or delayed activity and that they release continuously a predetermined amount of active ingredient.
- compositions of this type contain from 1.5% to 6% by weight of sodium lauryl sulfate relative to tiludronic acid (EP-A-336851).
- a preparation in capsules is obtained by mixing the active ingredient with a diluent and by pouring the mixture obtained into soft or hard capsules.
- Water dispersible powders or granules may contain the active ingredient in admixture with dispersing agents or wetting agents, or suspending agents, such as polyvinylpyrrolidone, as well as with sweeteners or correctors taste.
- the active principle can also be formulated in the form of microcapsules, optionally with one or more carriers or additives.
- compositions based on calcium salts are prepared according to pharmaceutical techniques well known to those skilled in the art; preferably these compositions will be optionally scored tablets or effervescent tablets or chewable tablets.
- tiludronic acid or one of its salts and / or solvates and the nutritive supplement necessary for a therapy cycle of 28 to 31 days as described above will be contained in the same packaging; the pharmaceutical compositions respectively containing tiludronic acid or one of its salts and / or solvates and the nutritive supplement could possibly be formulated in different colors or numbered, to facilitate the administration of this type of medicament in a long-term therapy.
- the daily dose of tiludronic acid or one of its salts and / or solvates to be administered varies according to the characteristics of the subject to be treated such as age, weight and severity of the conditions; in general the daily dose is between 10 and 400 g of tiludronic acid, advantageously between 30 and 300 mg, preferably 50, 75, 100, 125, 150, 175 or 200 mg, for example 50 or 200 mg per day.
- tiludronic acid is advantageously administered in the form of its disodium salt monohydrate or hemihydrate.
- tiludronic acid refers to tiludronic acid.
- the amount administered will be that corresponding to the dose of tiludronic acid desired.
- the daily dose of nutritional supplement depends on the type of substance administered and the patient's diet.
- the nutritional supplement is calcium
- the amount can vary between 200 and 2000 mg per day, advantageously 500 or 1000 mg per day, expressed in mg of Ca ++ .
- the therapy cycle described above must be repeated several times, as part of a long-term treatment, which can range from 6 months to several years.
- the treatment cycle should be repeated until the desired increase in bone mass is achieved.
- the present invention relates to a method of treatment and / or prevention of osteoporosis, which comprises the administration of tiludronic acid or one of its salts and / or solvates during a period of 7 days, followed by a rest period of 21-24 days during which a nutritional supplement, including calcium, can be administered.
- the present invention also relates to a method for the treatment and / or prevention of osteoporosis in mammals, which comprises administering to said mammals an effective amount of tiludronic acid or a salt thereof and / or pharmaceutically acceptable solvates and a nutritional supplement according to the following scheme:
- EXAMPLE 1 A Tablets are prepared having the following composition disodium tiludronate hemihydrate 58.6 mg (corresponding to 50 mg of tiludronic aci) lactose 10.06 mg sodium lauryl sulfate 1.125 mg crospovidone 3.75 mg methyl hydroxypropyl cellulose 1.3 125 mg 0.15 mg magnesium stearate
- the granulation is carried out using purified water which is eliminated in the following preparation steps.
- Tablets having the following composition are prepared: disodium tiludronate hemihydrate 234.5 mg (corresponding to 200 mg of tiludronic acid) lactose 40.15 mg sodium lauryl sulfate 4.5 mg crospovidone 15 mg methyl hydroxypropyl cellulose 5.25 mg magnesium stearate 0.6 mg
- the granulation is carried out using purified water which is eliminated in the following preparation steps.
- B. Tablets are prepared having the following composition (total Ca ++ 500 mg): calcium carbonate 1.25 g sucrose 0.85 g sodium chloride 0.02 g sodium saccharin 0.02 g polyethylene glycol 0.2 g bicarbonate sodium 1 g citric acid 1.65 g orange essence 0.02 g
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9414630A FR2727629A1 (fr) | 1994-12-06 | 1994-12-06 | Trousse pour cycle de traitement de l'osteoporose |
| FR9414630 | 1994-12-06 | ||
| PCT/FR1995/001596 WO1996017616A1 (fr) | 1994-12-06 | 1995-12-05 | Trousse pour cycle de traitement de l'osteoporose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0797444A1 true EP0797444A1 (fr) | 1997-10-01 |
Family
ID=9469504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP95941761A Withdrawn EP0797444A1 (fr) | 1994-12-06 | 1995-12-05 | Trousse pour cycle de traitement de l'osteoporose |
Country Status (20)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6432932B1 (en) | 1997-07-22 | 2002-08-13 | Merck & Co., Inc. | Method for inhibiting bone resorption |
| US5994329A (en) | 1997-07-22 | 1999-11-30 | Merck & Co., Inc. | Method for inhibiting bone resorption |
| SI1506041T1 (sl) | 2002-05-10 | 2008-02-29 | Hoffmann La Roche | Ibandronska kislina za zdravljenje in preprecevanje osteoporoze |
| CA2484494C (en) * | 2002-12-20 | 2009-05-12 | F. Hoffmann-La Roche Ag | High dose ibandronate formulation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE66608T1 (de) * | 1984-04-30 | 1991-09-15 | Procter & Gamble | Ausruestung fuer die behandlung der osteoporose. |
| US4761406A (en) * | 1985-06-06 | 1988-08-02 | The Procter & Gamble Company | Regimen for treating osteoporosis |
| JP4481368B2 (ja) * | 1992-06-30 | 2010-06-16 | 味の素株式会社 | 骨粗鬆症の治療用のためのホスホネート類の用途 |
| FR2694558B1 (fr) * | 1992-08-05 | 1994-10-28 | Sanofi Elf | Monohydrate du sel disodique de l'acide 4-chlorophénylthiométhylène bisphosphonique, sa préparation, les compositions pharmaceutiques en contenant. |
-
1994
- 1994-12-06 FR FR9414630A patent/FR2727629A1/fr active Granted
-
1995
- 1995-11-28 IL IL11616895A patent/IL116168A0/xx unknown
- 1995-11-30 ZA ZA9510184A patent/ZA9510184B/xx unknown
- 1995-12-04 TR TR95/01530A patent/TR199501530A1/xx unknown
- 1995-12-04 MA MA24086A patent/MA23737A1/fr unknown
- 1995-12-05 CN CN95196670A patent/CN1168634A/zh active Pending
- 1995-12-05 EP EP95941761A patent/EP0797444A1/fr not_active Withdrawn
- 1995-12-05 WO PCT/FR1995/001596 patent/WO1996017616A1/fr not_active Application Discontinuation
- 1995-12-05 JP JP8517359A patent/JPH10509729A/ja not_active Ceased
- 1995-12-05 CZ CZ971753A patent/CZ175397A3/cs unknown
- 1995-12-05 BR BR9509961A patent/BR9509961A/pt not_active Application Discontinuation
- 1995-12-05 AU AU43073/96A patent/AU4307396A/en not_active Abandoned
- 1995-12-05 KR KR1019970703784A patent/KR980700083A/ko not_active Withdrawn
- 1995-12-05 AR ARP950100438A patent/AR002946A1/es unknown
- 1995-12-05 CA CA002207028A patent/CA2207028A1/en not_active Abandoned
- 1995-12-05 FI FI972383A patent/FI972383A0/fi not_active Application Discontinuation
- 1995-12-05 SK SK685-97A patent/SK68597A3/sk unknown
- 1995-12-05 PL PL95320564A patent/PL320564A1/xx unknown
- 1995-12-05 HU HU9702097A patent/HUT77382A/hu unknown
-
1997
- 1997-06-05 NO NO972558A patent/NO972558L/no unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9617616A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9509961A (pt) | 1997-11-25 |
| AR002946A1 (es) | 1998-05-27 |
| WO1996017616A1 (fr) | 1996-06-13 |
| FR2727629A1 (fr) | 1996-06-07 |
| CA2207028A1 (en) | 1996-06-13 |
| ZA9510184B (en) | 1996-06-11 |
| TR199501530A1 (tr) | 1996-10-21 |
| PL320564A1 (en) | 1997-10-13 |
| MA23737A1 (fr) | 1996-07-01 |
| FI972383L (fi) | 1997-06-05 |
| FR2727629B1 (enrdf_load_stackoverflow) | 1997-02-28 |
| FI972383A7 (fi) | 1997-06-05 |
| SK68597A3 (en) | 1997-11-05 |
| MX9704105A (es) | 1997-09-30 |
| IL116168A0 (en) | 1996-01-31 |
| HUT77382A (hu) | 1998-04-28 |
| KR980700083A (ko) | 1998-03-30 |
| FI972383A0 (fi) | 1997-06-05 |
| NO972558D0 (no) | 1997-06-05 |
| NO972558L (no) | 1997-08-05 |
| CZ175397A3 (en) | 1997-10-15 |
| CN1168634A (zh) | 1997-12-24 |
| AU4307396A (en) | 1996-06-26 |
| JPH10509729A (ja) | 1998-09-22 |
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