EP1509238A1 - Composition contenant du calcium tiree de tissus osseux - Google Patents

Composition contenant du calcium tiree de tissus osseux

Info

Publication number
EP1509238A1
EP1509238A1 EP03741622A EP03741622A EP1509238A1 EP 1509238 A1 EP1509238 A1 EP 1509238A1 EP 03741622 A EP03741622 A EP 03741622A EP 03741622 A EP03741622 A EP 03741622A EP 1509238 A1 EP1509238 A1 EP 1509238A1
Authority
EP
European Patent Office
Prior art keywords
calcium
bone tissue
containing composition
bones
process according
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Withdrawn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
EP03741622A
Other languages
German (de)
English (en)
Inventor
Dick Teune
Johannes Adrianus Hage
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.)
Gelatine Smits Beheer BV
Original Assignee
Gelatine Smits Beheer BV
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 Gelatine Smits Beheer BV filed Critical Gelatine Smits Beheer BV
Publication of EP1509238A1 publication Critical patent/EP1509238A1/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Withdrawn legal-status Critical Current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
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
    • 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

Definitions

  • the present invention relates to a calcium-containing composition obtained from animal bone tissue for treating disorders connected with the growth or healing of bones or bone tissue-
  • a composition is known from EP 0 255 565.
  • the known composition has a total protein content of at least 30.6 wt. %, the collagen content being at least 23.4 wt. %.
  • the known composition has a calcium content of maximally 23.4 wt. %, and the particle size of the composition can be 300 ⁇ m.
  • the calcium-containing compositions known from WO 94/26283 are based on organic or inorganic calcium salts, for example in the form of aragonite or calcite, possibly obtained from external skeletons of corals and crustaceans.
  • disorders connected with the growth or healing of bones or bone tissue is understood to mean not only disorders relating to an insufficient mineralisation or a decreasing mineralisation (decalcification), such as a dysplasia, an osteodystrophy, a paradontal disease or osteoporosis, but also the local healing of bone fractures.
  • a calcium-containing composition having a matrix structure of natural bone tissue and a very high biological availability for a better and more efficient treatment of such disorders.
  • Known calcium-containing composition based on calcium salts such as calcium chloride and calcium carbonate lack the phosphate ion that is essential for the building up of bone tissue.
  • calcium-containing compositions obtained from the exoskeleton of lower animals does not have the suitable matrix structure and the required high biological availability. According to the present invention, this need is met by a calcium-containing composition, which is characterised in that the composition is a calcium phosphate complex having a protein content of less than 25 wt. % and that the composition has a matrix of natural bone tissue.
  • composition according to the present invention is the fact that there is no risk of contaminations with, for example, BSE causing agents, in particular because of the low protein content (obtained by using the extraction method to be described hereinafter).
  • the protein content amounts to less than 10 wt. %.
  • the calcium content amounts to more than 30%.
  • the bone tissue may be obtained from various animal species, for example cattle, poultry or pigs.
  • the calcium phosphate complex is obtained from natural porcine bone tissue. Not only is the matrix structure of porcine bone tissue more similar to the matrix structure of human bone tissue, but in addition there is no danger of contamination with BSE causing agents when porcine bone tissue is used. Research has shown that the biological availability is higher if the calcium phosphate complex has been sufficiently reduced in size, and preferably the particle size of the obtained calcium complex is maximally 75 ⁇ m.
  • the present invention also relates to a process for preparing a calcium-containing composition starting from natural bone tissue, comprising the defatting and grinding of bones. Such a method is generally known.
  • the process according to the invention is characterized in that the bones, which may be crushed to form small pieces, are defatted at a temperature of less than 90 "C, after which proteins are extracted by first treating the bones with a liquid having an acidic pH value and subsequently treating the bones with steam, after which the bones are grinded.
  • the bones are dried with heated air following the defatting step and prior to the extracting step.
  • a very good extraction is obtained if the liquid used in the extracting step has a pH value of 2-5.
  • a process step which leads to good extraction results and which is nevertheless sufficiently mild to maintain a natural matrix structure of bone tissue comprises treating with steam under pressure of at least 3 bar for a period of at least 20 minutes.
  • the bones are washed with water having a temperature of maximally 80 °C following the treatment with steam and before the grinding step.
  • the present invention also relates to a pharmaceutical preparation on the basis of a calcium-containing composition for treating disorders connected with the growth or healing of bones or bone tissue, which preparation comprises at least one active ingredient and one auxiliary substance, wherein the preparation contains a calcium- containing composition according to the present invention as the active ingredient.
  • the present invention relates to a pharmaceutical preparation on the basi's of a calcium-containing composition for treating osteoporosis, which comprises at least one active ingredient and one auxiliary substance, wherein the preparation contains a calcium- containing composition according to the present invention as the active ingredient.
  • An auxiliary substance may be added for the purpose of improving the running properties; in this connection, good results have been obtained with carboxylmethyl cellulose as the auxiliary substance.
  • the calcium-containing composition incorporated in a pharmaceutical preparation can be administered, for example orally, to a human or animal patient, in amounts and at a frequency to be determined by the physician in attendance, inter alia depending on the gravity of the disorder in question or the extent of the required healing, the age and the body weight of the patient.
  • a soft capsule containing an amount of a calcium-containing composition corresponding to 100 mg of calcium ions may be orally administered to the patient, four times a day.
  • Alternative dosage forms are hard capsules, each containing 125 mg of calcium ions or granulates containing 30 wt.% of calcium ions.
  • Administration in liquid form for example in the form of a suspension in a buffered citrate solution, is also suitable.
  • porcine bones An amount of 100 g of porcine bones was crushed into pieces of maximally 2 cm.
  • the porcine bones were defatted with water at 80 ° C, followed by the removal of the soft material and the finest bone particles. Finally, the defatted bone material was dried with heated air.
  • the defatted and dried bone material was introduced into an autoclave for carrying out the extraction process and was treated with a solution of 0.1 M sulphuric acid, for a period of 1 hour. The thus obained maceration liquid was removed. Subsequently, the bone material was saturated with steam, after which the pressure was increased to 3 bar, which pressure was maintained for 20 minutes. After expansion, the treated bone material was washed with water having a temperature of 60 "C. This extraction procedure was repeated seven times.
  • the defatted and extracted bone material was dried with heated air (60 °C) and finally ground in a ball mill to a particle size of maximally 75 ⁇ m.
  • the fat content was 1%.
  • the calcium content was 32%.
  • the calcium composition that was eventually obtained was subjected to a test regarding the biological availability thereof.
  • the calcium composition was stirred in a slightly acidic cyclic acid solution at 65 ° C for one hour, and was subsequently subjected to filtration.
  • the calcium content of the filtrate was determined.
  • the determination of the biological availability or the capacity of biological incorporation was carried out substantially as described in Dellaert B.N. et al , Netherlands Journal of Agricultural Science, 38, pp. 555-566 (1990). The biological availability was shown out to be 97.2%.
  • Example 2 The determination of the biological availability or the capacity of biological incorporation was carried out substantially as described in Dellaert B.N. et al , Netherlands Journal of Agricultural Science, 38, pp. 555-566
  • Example 2 Using the calcium-containing composition based on a calcium phosphate complex obtained from porcine bone tissue, obtained as described in Example 1, a pharmaceutical preparation suitable for treating disorders connected with the growth or healing of bones or bone tissue was prepared. An amount of 99 g of the calcium-containing composition obtained by using the method described in Example 1 was mixed with an amount of 1 gram of carboxylmethylcellulose.
  • the pharmaceutical preparation was administered orally in the form of hard capsules (each containing an amount of calcium- containing composition corresponding to 125 mg of calcium ions) to 50 adult female volunteers, using a dosing scheme of four times one capsule, distributed over the day. Two other groups of 50 volunteers each were given a known calcium composition and a placebo, respectively. The test was carried out as a double-blind test. The test results showed an increased biological availability and an excellent incorporation of calcium obtained by using the calcium composition according to the invention.
  • the pharmaceutical preparation as prepared was shown to be suitable for helping to treat disorders connected with the growth of bones or bone tissue, such as, by way of example, osteoporosis.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Cette invention se rapporte à une composition contenant du calcium obtenue à partir de tissus osseux d'animaux et servant à traiter les troubles liés à la croissance ou à la cicatrisation des os ou des tissus osseux. Cette composition est constituée par un complexe phosphate et calcium avec une teneur en protéines inférieure à 25 % en poids et elle possède une matrice de tissus osseux naturels. Cette invention se rapporte en outre à un procédé servant à préparer une telle composition contenant du calcium faite de tissus osseux naturels ainsi qu'à une préparation pharmaceutique à base de cette composition
EP03741622A 2002-05-31 2003-05-28 Composition contenant du calcium tiree de tissus osseux Withdrawn EP1509238A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
NL1020729 2002-05-31
NL1020729A NL1020729C2 (nl) 2002-05-31 2002-05-31 Calciumbevattende samenstelling, werkwijze voor het bereiden daarvan, en farmaceutisch preparaat op basis van de samenstelling.
PCT/NL2003/000400 WO2003101471A1 (fr) 2002-05-31 2003-05-28 Composition contenant du calcium tiree de tissus osseux

Publications (1)

Publication Number Publication Date
EP1509238A1 true EP1509238A1 (fr) 2005-03-02

Family

ID=29707800

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03741622A Withdrawn EP1509238A1 (fr) 2002-05-31 2003-05-28 Composition contenant du calcium tiree de tissus osseux

Country Status (4)

Country Link
EP (1) EP1509238A1 (fr)
AU (1) AU2003273569A1 (fr)
NL (1) NL1020729C2 (fr)
WO (1) WO2003101471A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL3634433T3 (pl) 2017-06-01 2024-03-04 Fundació Institut De Bioenginyeria De Catalunya (Ibec) Cząstki wapnia o kontrolowanym uwalnianiu jonów, sposób ich wytwarzania i zastosowanie

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3626414C2 (de) * 1986-08-05 1994-11-10 Robapharm Ag Präparat zur Stimulierung von Chondrocyten und Osteoblasten (Ossein-Hydroxyapatit-Komplex), Verfahren zu seiner Herstellung und dieses enthaltende Arzneimittel

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03101471A1 *

Also Published As

Publication number Publication date
AU2003273569A1 (en) 2003-12-19
WO2003101471A1 (fr) 2003-12-11
NL1020729C2 (nl) 2003-12-02

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