EP2575796A1 - Formulations comprenant du calcium, de la vitamine d et de la vitamine k pour traiter l'ostéoporose - Google Patents

Formulations comprenant du calcium, de la vitamine d et de la vitamine k pour traiter l'ostéoporose

Info

Publication number
EP2575796A1
EP2575796A1 EP11749578.8A EP11749578A EP2575796A1 EP 2575796 A1 EP2575796 A1 EP 2575796A1 EP 11749578 A EP11749578 A EP 11749578A EP 2575796 A1 EP2575796 A1 EP 2575796A1
Authority
EP
European Patent Office
Prior art keywords
effervescent
formulation
formulation according
vitamin
formulation comprises
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Withdrawn
Application number
EP11749578.8A
Other languages
German (de)
English (en)
Inventor
Mahmut Bilgic
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP2575796A1 publication Critical patent/EP2575796A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • 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
    • A61K33/10—Carbonates; Bicarbonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent

Definitions

  • the present invention relates to formulations comprising calcium, vitamin D and vitamin K; and use of said formulations in prophylaxis and treatment of osteoporosis and related diseases.
  • Bone loss or in other terms “osteoporosis” is defined as a disease characterized by liability to bone fracture and increased risk of bone fracture as a consequence of low bone mass and deterioration of bone micro architecture. The disease does not generally result in death; however, it is a major health problem affecting life quality. Although osteoporosis is mostly seen in spine, hip and wrist; all the bones in the body are affected by the disease. 80% of the patients are female though the disease is encountered in both genders. Postmenopausal women lose 0,7-2% of total bone mass annually while this ratio is 0,5-0,7% for men. In parallel with this, total bone mass loss in men and women between 45-70 years of age is 15-30%. Some studies conducted nowadays indicate that insufficient calcium intake in childhood may increase the risk of osteoporosis later in life.
  • calcium taken by diet plays a significant role in prophylaxis of osteoporosis.
  • calcium absorption is reduced in postmenopausal term due to physical features of calcium and other factors.
  • One of the most important problems encountered in calcium intake is that calcium salts in all calcium sources do not dissolve at an equal rate or present desired bioavailability. Calcium salts have low water solubility. They are dissolved relatively better in gastric acid; however, carbon dioxide produced causes gas and pain in the stomach. Furthermore, gastric acid is reduced due to gastric acid inhibitors used in later ages and therefore calcium leaves the stomach without being dissolved.
  • Vitamin D is a fat-soluble hormone precursor and the studies conducted have indicated that efficient amounts of vitamin D increases calcium absorption.
  • Bone is a living tissue which is continuously being created and destroyed. This creation and destruction process is balanced in young, healthy individuals. An increase in the activity of osteoclasts that are responsible for destruction unbalances this process. Vitamin K plays a key role in reducing this increased activity of osteoclasts and therefore preventing bone degradation.
  • Cells that are responsible for bone formation are osteoblasts. Osteoblasts produce a protein named osteocalcin and calcium is stored in bones when this protein is activated.
  • vitamin K is required for osteocalcin to bind calcium and vitamin D is required for osteocalcin production.
  • the tablet formulations comprising vitamin calcium, vitamin D 3 and vitamin K that exist on the market now are formulations developed in line with this purpose.
  • effervescent formulations comprising calcium, vitamin D and vitamin K are user-friendly, have fewer side effects and present higher bioavailability compared with the existing tablet formulations; therefore, they display higher efficiency in the prophylaxis and treatment of osteoporosis and related diseases.
  • the present invention relates to effervescent formulations comprising calcium, vitamin D and vitamin K.
  • Effervescent formulation of the present invention can be in powder, granule, pellet, micro tablet or tablet form. Effervescent formulation of the present invention is preferably in tablet form.
  • Calcium used in the formulation of the present invention is preferably in salt form.
  • Calcium comprised in the formulation of the present invention can be selected from calcium, carbonate, chloride, phosphate, citrate, lactate, glubionate, gluceptate, gluconate salts though it is preferably carbonate salt.
  • Formulation of the present invention comprises 5-60% calcium or calcium salt by weight.
  • Formulation of the present invention comprises 200-2000 mg calcium or calcium salt in an equal amount to this.
  • Vitamin D comprised in the formulation of the present invention can be vitamin D 2 (ergocalciferol) or vitamin D 3 (cholecalciferol) though it is preferably vitamin D 3 (cholecalciferol).
  • Formulation of the present invention comprises 0,01-15% vitamin D by weight.
  • Formulation of the present invention comprises 200-1000 IU vitamin D.
  • Vitamin K comprised in the formulation of the present invention is vitamin K ⁇ , K 2 or a combination thereof.
  • Formulation of the present invention comprises 0,001 -5% vitamin K by weight.
  • Formulation of the present invention comprises 5-200 ⁇ g vitamin K.
  • the inventors added malic acid (powder) into the effervescent formulation comprising calcium, vitamin D and vitamin K in order to provide sufficient clarity of the solution after the formulation is dissolved.
  • the present invention relates to effervescent formulations comprising calcium, vitamin D and vitamin K and malic acid (powder).
  • Amount of the malic acid comprised in the formulation of the present invention is in the range of 3-20% by weight.
  • the formulation of the present invention comprises calcium, vitamin D and vitamin K as the active agents, and an effervescent couple to provide water solubility characteristic.
  • effervescent couple refers to use of an acidic agent and a basic agent together.
  • the pharmaceutically acceptable acidic agent of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, phosphoric acid, propionic acid, malic acid, tartaric acid or combinations thereof.
  • the pharmaceutically acceptable acidic agent of the present invention is preferably citric acid, malic acid or a combination thereof.
  • the pharmaceutically acceptable basic agent of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate or combinations thereof.
  • the pharmaceutically acceptable basic agent of the present invention is preferably sodium carbonate or sodium hydrogen carbonate.
  • the formulation of the present invention in effervescent form can comprise pharmaceutically acceptable excipients in addition to calcium, vitamin D and vitamin K.
  • the effervescent formulation of the present invention can optionally comprise one or more of the excipients including binder, glidant, lubricant, diluent, disintegrant, flavoring agent, sweetener, coloring agent, anti-foam agent, stabilizing agent.
  • the said binder can be selected from a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatin; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone), polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol, and water or a combination thereof.
  • the binder used in the formulation of the present invention is preferably lactose, povidone, polyethylene glycol or a combination thereof.
  • the said glidant can be selected from a group comprising sodium benzoate, sodium chloride, sodium acetate, sodium fumarate, carbowax 4000, L-leucine(17), polyethylene glycol or a combination thereof though it is preferably polyethylene glycol.
  • PEG that the formulation of the present invention comprises is PEG 4000, PEG 6000 or a combination thereof.
  • Polyethylene glycol that the formulation of the present invention comprises is more than 2% by weight.
  • the said lubricant can be selected from a group comprising talc, magnesium stearate, stearic acid, sodium stearil fumarate, polyoxyethylene glycol, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof.
  • the said diluent can be selected from a group comprising lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch or a combination thereof.
  • the said disintegrant can be selected from a group comprising starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose sodium or microcrystalline cellulose; polyvinylpyrrolidone; crospovidone; alginic acid and its salts; clays such as xanthan gum or Veegum; ion exchange resins or a combination thereof.
  • the said flavoring agent can be selected from a group comprising natural aroma oils (peppermint oil, wintergreen oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, menthane, anethole, methyl salicylate, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, alpha irisone, marjoram, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, thymol, linalol, cinnamaldehyde glycerol acetal, N-substituted p- menthane-3-carboxamide, 3,1-methoxy propane 1,2-diol or a combination thereof though it is preferably lemon, orange, blackberry flavor or a combination thereof.
  • natural aroma oils peppermint oil, wintergreen oil, clove bud oil, parsley oil,
  • the said sweetener can be selected from a group comprising sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulfame potassium, aspartame, D-tryptophane, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof though it is preferably sucralose, lactose, glucose, mannitol, sorbitol or a combination thereof.
  • the said coloring agent can be selected from a group comprising carotenoids and chlorophyl or a combination thereof.
  • the said antifoam agent can be selected from a group comprising simethicone emulsion and dimethyl siloxane, silicon oil or a combination thereof.
  • the said stabilizing agent and/or agents can be selected from a group comprising antioxidants, chelating agents, alkalinizing agents and photoprotective agents.
  • the antioxidants can be selected from substances including butylated hydroxyanisole (BHA), sodium ascorbate, butylhydroxytoluene (BHT), sodium sulphite, gallates (such as propyl gallate), tocoferole, citric acid, malic acid, ascorbic acid, acetylcysteine, fumaric acid, lecithin, ascorbyl palmitate, ethylenediamine tetraacetate or a combination thereof.
  • BHA butylated hydroxyanisole
  • BHT butylhydroxytoluene
  • gallates such as propyl gallate
  • tocoferole citric acid, malic acid, ascorbic acid, acetylcysteine, fumaric acid, lecithin, ascorbyl palmitate, ethylenediamine tetraacetate or a combination thereof.
  • the chelating agents can be selected from a group comprising disodium EDTA, edetic acid, citric acid, sodium citrate, potassium citrate or a combination thereof.
  • the alkalinizing agents can be selected from alkali metal salts such as sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium aluminate; alkaline earth metal salts such as calcium carbonate, calcium hydroxide, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium acetate, calcium gluconate, calcium glycerophospate, magnesium carbonate, magnesium hydroxide, magnesium sulphate, magnesium acetate, magnesium silicate, magnesium aluminate; and primary, secondary and tertiary amines, cyclic amines; ⁇ , ⁇ '- dibenzyl ethylenediamine, dietanolamine, ethylenediamine, meglumine, monosodium glutamate, pola
  • the photoprotective agents can be selected from metal oxides such as titanium oxide, iron oxide and zinc oxide or a combination thereof.
  • the effervescent formulation comprises;
  • Vitamin D in the range of 0,01 - 10% by weight
  • Vitamin K in the range of 0,001 -5% by weight
  • Polyethylene glycol in the range of 2- 10% by weight
  • Sweetener in the range of 0-5% by weight
  • osteoporosis and related diseases comprises diseases such as osteoporosis; bone fracture including vertebral column and hip bones in postmenopausal women; bone fracture in men; idiopathic osteoporosis; osteoporosis resulting from various diseases; steroid and glucocorticoid-induced osteoporosis; osteopenia; osteomalacia; osteogenesis imperfecta; osteochondrodisplasia; sudeck atrophy; rheumatoid arthritis; atherosclerosis; Paget' s disease; metastasis of malignant tumors to bones; hypercalcemia; or hyperthyroidism.
  • prophylaxis of the disease refers to prevention of abovementioned diseases by administering said formulations to healthy people. This term also comprises use of said formulation in people who are in the first stage of the disease.
  • treatment of the disease refers to use of the formulation of the present invention for treatment purposes in people diagnosed with osteoporosis or osteoporosis-related diseases. All the components used in scope of the present invention are pharmaceutically acceptable.
  • pharmaceutically acceptable refers to the component's suitability for use in people; its having few or no side effects (toxicity, irritation, allergic response) and its providing the user an evident benefit.
  • the effervescent formulation of the present invention can be produced by direct compression, wet granulation and/or dry granulation methods applied conventionally.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des formulations comprenant du calcium, de la vitamine D et de la vitamine K; et l'utilisation de ces formulations pour prévenir et traiter l'ostéoporose et les maladies associées.
EP11749578.8A 2010-06-03 2011-06-02 Formulations comprenant du calcium, de la vitamine d et de la vitamine k pour traiter l'ostéoporose Withdrawn EP2575796A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201004465 2010-06-03
PCT/TR2011/000151 WO2011152810A1 (fr) 2010-06-03 2011-06-02 Formulations comprenant du calcium, de la vitamine d et de la vitamine k pour traiter l'ostéoporose

Publications (1)

Publication Number Publication Date
EP2575796A1 true EP2575796A1 (fr) 2013-04-10

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP11749578.8A Withdrawn EP2575796A1 (fr) 2010-06-03 2011-06-02 Formulations comprenant du calcium, de la vitamine d et de la vitamine k pour traiter l'ostéoporose

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Country Link
EP (1) EP2575796A1 (fr)
WO (1) WO2011152810A1 (fr)

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Publication number Priority date Publication date Assignee Title
GB201203705D0 (en) 2012-03-02 2012-04-18 Kappa Bioscience As Prodrugs
GB201314245D0 (en) * 2013-08-08 2013-09-25 Kappa Bioscience As Provitamins
US9439913B1 (en) * 2013-11-15 2016-09-13 MVW Nutritionals, Inc. Fat-soluble vitamin formulations
EP3139904B1 (fr) 2014-05-05 2021-03-03 Basf Se Formulation de vitamine liposoluble
FR3025104B1 (fr) * 2014-08-29 2017-11-24 Hy-Nutrition Bolus a liberation immediate
KR101683635B1 (ko) 2014-12-29 2016-12-09 가천대학교 산학협력단 락테이트 금속염을 포함하는 암 치료용 약학 조성물
US20180015122A1 (en) * 2016-07-14 2018-01-18 Companion Supplements, LLC Pharmaceutical composition effective in preventing adverse effects associated with the use of glucocorticoids
EP3737363A4 (fr) 2018-01-12 2021-10-20 Metimedi Pharmaceuticals Co., Ltd Méthodes de traitement de maladies inflammatoires chroniques
CN112741841A (zh) * 2019-10-29 2021-05-04 湖北真奥医药研究院有限公司 三维钙自乳化泡腾剂组合物及其制剂的制备方法
CN110892991A (zh) * 2019-12-27 2020-03-20 北京康比特体育科技股份有限公司 一种增加骨密度的组合物及其制备方法和用途
CN112353813A (zh) * 2020-12-10 2021-02-12 浙江艾兰得生物科技有限公司 一种补钙效果好的维生素d和维生素k软胶囊

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BG695Y1 (bg) * 2000-01-21 2004-10-29 "Кенди" Оод Препарат за профилактика и лечение на костни патологии
DE20306555U1 (de) * 2003-04-26 2003-10-09 Bartz, Volker, 35440 Linden Calcium, Vitamin D und Vitamin K Mischung zur Prävention und Behandlung der Osteoporose
JPWO2005046702A1 (ja) * 2003-09-19 2007-05-24 サンスター株式会社 歯槽骨の吸収及び歯根膜喪失を抑制する方法及びそれに用いる内服組成物
DE202004005428U1 (de) * 2004-04-06 2004-06-17 Weber & Weber Gmbh & Co. Kg Mikronährstoffkombinationsprodukt, geeignet für die nutritive Ergänzung bei einem erhöhten Bedarf an Mikronährstoffen insbesondere bei Personen mit Osteoporose
ES2395862T3 (es) * 2006-09-28 2013-02-15 Bayer Consumer Care Ag Mezcla de sales de hierro y de cobre para enmascarar el sabor metálico

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Also Published As

Publication number Publication date
WO2011152810A1 (fr) 2011-12-08

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