Process for preparing high purity bone mineral

Details Process for preparing high purity bone mineral Process for preparing high purity bone mineral

1990-04-02

1992-12-01

Page, Thurman K.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Implant or insert

424422, 424484, 514774, 530350, 530353, 530840, 623 16, A61K 914, A61K 4742, A61K 3712, A61K 228

Patent

active

051679612

DESCRIPTION:

BRIEF SUMMARY
This invention relates to bone mineral products of large specific surface area.
Bones from slaughtered animals are an inexpensive raw material available in large quantities. They contain 50 to 60% of very fine crystallites of a form of hydroxylapatite bonded by collagenic tissue and containing significant qualities of proteinaceous and other matter as well as associated fat and muscle tissues. Such a hydroxylapatite, if it could be isolated in a pure state without changing its essential crystal structure, would represent a highly biocompatible remodelling bone implant material.
Natural bone mineral comprises hydroxyapatitelike crystallites with a particular degree of crystallinity, habit and size (irregular platelike morphology, 5-10nm in thickness 10-50 nm in length) and surface chemistry resulting from the calcium to phosphate ratio (37.5-38.0% calcium and 15.5-5-19.0% phosphorus). The inorganic phase of bone contains porosity including ultrastructural interstices (10-100 nm) between the crystallites occurring naturally and produced by removal of the organic phase, and microscopic spaces (1-20 microns) including osteocyte lacunae, canaliculi, vascular channels, volkman's canals, and the canals of haversian systems (100-500 nm). The specific surface area, which is a measure of porosity is in the range 50 to 100 m.sup.2 /gm as determined by mercury porosimetry. The crystallinity of bone mineral can be characterized by X-ray diffraction and the porosity and crystallite morphology and size by electron microscopy. We have found that the composition and structure of natural bone mineral cannot be duplicated by calcium phosphate products formed in vitro or by naturally occurring hydroxyapatites prepared previously.
Hitherto two methods for the purification of natural bone mineral have been proposed namely calcination and solvent extraction.
The temperatures needed during calcination for the incineration of the organic constituents of the bones are rather high. This leads to extensive recrystallization of the mineral part with formation of much coarser crystals The so formed material exhibits a small specific surface and is not superior to any chemically precipitated hydroxylapatite.
It should be emphasized that bone mineral which has been subjected to a treatment which results in significant increase in crystal size is much less readily remodelled on implantation since osteoclasts and osteoblasts cannot readily perform on such large crystals the dual function of mineral resorption and generation of new bone. Such implanted inserts may thus remain unchanged indefinitely eventually giving rise to undesirable effects. On the other hand, many synthetic tricalcium phosphate products tend to be resorbed too rapidly for osteoblasts to regenerate new bone.
In the prior extraction process the proteins are extracted from degreased bone with a suitable solvent. The resulting bone mineral is then washed to remove the solvent.
Stegemann and Jung (Hoppe Seyler's Z. physiol. Chem. 320 (196) 272) used formamide for the protein extraction. This method proved to be impractical, the solvent being unstable under the conditions of hot extraction.
The sometimes recommended extraction with hot water instead of water washing after extraction was found to promote undesirable crystal growth (Skinner, Kempur and Pak: Calf. Tiss. Res. 10 (1972) 257).
The generally preferred method according to the prior art consists of the extraction of degreased bone with boiling ethylene diamine followed by washing with water. This method has been introduced by Willia's[and Irvine Jnr. (Science 119 (1954) 771) and later used by Losse and Hurley (Nature 177 (1956) 1032; Military Medicine (1957) 101) and by Kershaw (The Pharmaceutical Journal 190 (1963) 537). A patent for this process has been granted to Armour & Co. (U.S. Pat. No. 2,968,593 (1961)).
It has generally been claimed that extraction with ethylenediamine yields pure bone mineral. However, on repetition of this method we have always found that the products contain between 0.1% and 1% of organic

REFERENCES:
patent: 2968593 (1961-01-01), Rapkin
patent: 4314380 (1982-02-01), Miyata et al.
patent: 4434094 (1984-02-01), Seyedin et al.
patent: 4455256 (1984-06-01), Urist
patent: 4587268 (1986-05-01), Pfirrmann
patent: 4654464 (1987-03-01), Mittelmeier et al.
Stegemann, et al. "Uber die anorganische Knochensubstanz nach Formamidaufschluss", Bd. 320 (1960) 272.
Skinner, et al., Calc. Tiss. Res. 10 (1972) 257.
Williams, et al., Science 119 (1954) 771.
Losse, et al., Nature 177 (1956) 1032.
Hurley, et al., Military Medicine (1957) 101.
Kershaw, The Pharmaceutical Journal 190 (1963) 537.
International Search Report (WO 86/07265).
International Search Report (WO 89/01347).
Partial European Search Report (EPA 147,021).
Solomons, T. W. Graham, Organic Chemistry, 2nd Ed. 1980.

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