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

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• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Epidemiology (AREA)
• Physical Education & Sports Medicine (AREA)
• Rheumatology (AREA)
• General Chemical & Material Sciences (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Inorganic Chemistry (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)

Publications (1)

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• 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 MA MA24086A patent/MA23737A1/fr unknown
  • 1995-12-04 TR TR95/01530A patent/TR199501530A1/xx unknown
  • 1995-12-05 CN CN95196670A patent/CN1168634A/zh active Pending
  • 1995-12-05 WO PCT/FR1995/001596 patent/WO1996017616A1/fr not_active Application Discontinuation
  • 1995-12-05 CA CA002207028A patent/CA2207028A1/en not_active Abandoned
  • 1995-12-05 SK SK685-97A patent/SK68597A3/sk unknown
  • 1995-12-05 CZ CZ971753A patent/CZ175397A3/cs unknown
  • 1995-12-05 PL PL95320564A patent/PL320564A1/xx unknown
  • 1995-12-05 AU AU43073/96A patent/AU4307396A/en not_active Abandoned
  • 1995-12-05 BR BR9509961A patent/BR9509961A/pt not_active Application Discontinuation
  • 1995-12-05 AR ARP950100438A patent/AR002946A1/es unknown
  • 1995-12-05 HU HU9702097A patent/HUT77382A/hu unknown
  • 1995-12-05 JP JP8517359A patent/JPH10509729A/ja not_active Ceased
  • 1995-12-05 KR KR1019970703784A patent/KR980700083A/ko not_active Application Discontinuation
  • 1995-12-05 EP EP95941761A patent/EP0797444A1/de not_active Withdrawn
• 1997
  • 1997-06-05 NO NO972558A patent/NO972558L/no unknown
  • 1997-06-05 FI FI972383A patent/FI972383A/fi not_active Application Discontinuation

Non-Patent Citations (1)

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