Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Phosphorus or phosphorus compound
Patent
1995-04-05
2000-02-15
Pak, John
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Phosphorus or phosphorus compound
424601, 424603, 424604, 424605, 424606, 424678, 424681, 424682, 424683, 424686, 424692, 424697, 424 57, 514 77, 514 81, 623 11, 623 16, 106 35, A61K 3306, A61K 6033, C01B 2532, A61L 2700
Patent
active
060249854
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to materials useful in producing bone mineral or similar material; to their preparation; and to their use.
Bone has organic and inorganic constituents. Most of the strength is due to the inorganic material, of which the major part is crystalline calcium phosphate, particularly hydroxyapatite, Ca.sub.5 (OH) (PO.sub.4).sub.3. This crystalline material is strong, stable and essentially insoluble.
SUMMARY OF THE INVENTION
We have now found certain substantially amorphous materials that can be transformed under controlled conditions into crystalline bone material which may be of natural type or similar strong, stable material. Thus in one aspect the invention concerns use of certain precursor materials in the manufacture of a composition for use in a therapeutic technique in which bone is built up in vivo by transformation of the composition to produce bone material.
The precursor materials contain, as principal inorganic constituents, amorphous non-stoichiometric compounds containing calcium and phosphate ions. The phosphate ions may be mainly or wholly derived from phosphoric acid (H.sub.3 PO.sub.4); they may include a proportion of ions derived from pyrophosphoric acid (H.sub.4 P.sub.2 O.sub.7). Generally the compounds contain magnesium ions.
The precursor materials may be essentially inorganic, particularly when made synthetically. Alternatively they may include organic components. These can be deliberately included in synthetic materials, or be naturally present in naturally-derived materials.
Generally, the number of moles of magnesium Der mole of calcium is in the range 0.001 to 1; for example 0.01 to 0.40 and preferably 0.1 to 0.16
Material may be synthesised by bringing together calcium ions, magnesium ions, and phosphate ions in a buffer solution under conditions-such that a material of desired composition is precipitated. Other components can be included in the reaction solution if desired.
Naturally-derived materials can be prepared from naturally-occurring deposits of amorphous calcium/magnesium/phosphate minerals. Suitable deposits occur in the soft tissue of many invertebrates (see. e.g. G. L. Becker et al., J. Cell Biology, (1974), 61, 316-326 at page 322 and references cited therein), notably the intracellular granules from the digestive glands of various invertebrates, particularly crabs and snails e.c. as described in K. Simkiss et al, j.Inora.Biochem, (1990), 39, 17-23, and G. L. Becker et al, op cit. Thus as described by Simkiss et al, granules can be extracted from C.maenas by homogenisation of the digestive gland and centrifugation in water to afford a clean white product. This product consists largely of inorganic phosphate, with the metal ions being mainly calcium but with some magnesium (the molar ratio being about 9: 1). The phosphate includes ions derived from phosphoric and pyrophosphoric acids, primarily from phosphoric acid. There are also organic components, mainly adenosine phosphates. (In general, such granule-derived material may contain significant amounts of nucleosides and glycoproteins.)
Materials may be prepared or selected which contain different proportions of one or more crystallisation inhibitor components such as magnesium and/or pyrophosphate and/or organic components, in order to control the rate of conversion to bone material under predetermined (generally physiological) conditions. At its simplest, a precursor material is an amorphous composition which contains calcium and phosphate ions as primary constituents together with inhibitor components (notably magnesium and/or pyrochosphate ions) which inhibit its transformation to a crystalline form (generally based on hydroxyapatite). In use the precursor material gradually loses inhibitor components (in particularly, magnesium ions) by leaching action to ambient body fluids, and undergoes transformation into crystalline hydroxyapatite. Where pyrophosphate ions are used as crystallisation inhibitor the molar ratio of P.sub.2 O.sub.7 to PO.sub.4 is in the r
REFERENCES:
patent: Re33211 (1990-05-01), Brown et al.
patent: 2041473 (1936-05-01), Janota, Jr.
patent: 4113500 (1978-09-01), Ebihara et al.
patent: 4684673 (1987-08-01), Adachi
patent: 4917702 (1990-04-01), Scheicher
patent: 5037639 (1991-08-01), Tung
patent: 5522893 (1996-06-01), Chow et al.
patent: 5650176 (1997-07-01), Lee et al.
Chemical Abstracts 110:87229r, Mar. 1989.
Eidelman, N. et al., "The effect of pyrophosphate concentrations on calcium phosphate growth on well-crystallized octacalcium phosphate and hydroxyapatite seed crystals," J. Cryst. Growth, vol. 108(1-2), pp. 385-393, 1991.
Chemical Abstracts 114:154095, 1991.
Eidelman, N. et al., "Selective inhibition of crystal growth on octacalcium phosphate and nonstoichiometric hydroxyapatite by pyrophosphate at physiological concentration," J. Cryst. Growth, vol. 113(3-4), pp. 643-652, 1991.
Chemical Abstracts 115:252917, 1991.
Thomas, S.A., "Effects of some ions on the conversion of amorphous calcium phosphate to calcium hydroxyapatite in aqueous medium," Bull. Chem. Soc. Ethiop., vol. 5(1), pp. 11-20, 1991.
Chemical Abstracts 116:224953, 1992.
Nancollas, G.H. et al., "The precipitation of calcium phosphate in the presence in the presence of magnesium," Croat. Chem. Acta, vol. 48(4), pp. 431-438, 1976.
Chemical Abstracts 86:81796, 1977.
Simkiss Kenneth
Taylor Marina Gloria
Pak John
University of Reading
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