Methods for Carbonate Surface Coating and Related Bone Void Filler Compositions

Abstract

Bone void filler compositions and methods for preparation to provide substrates with carbonate surface coatings to promote bone growth.

Claims

1. A method of using comparative calcium salt solubilities to prepare a bone void filler substrate comprising calcium particles thereon, said method comprising: providing a carbonatable calcium salt precursor component having a water solubility; applying said precursor component to a bone void filler substrate; and treating said applied precursor component with a transformation component selected from alkali metal hydroxide and alkali metal carbonate components to provide on said substrate a calcium component having a water solubility less than said precursor component water solubility, said calcium component selected from calcium hydroxide and calcium carbonate particles.

2. The method of claim 1 wherein said calcium salt precursor component is selected from calcium chloride, calcium oxide and calcium acetate.

3. The method of claim 1 wherein said transformation component is selected from sodium hydroxide and sodium carbonate.

4. The method of claim 1 wherein said calcium component is calcium hydroxide, and said transformation component is sodium hydroxide, said calcium component having a water solubility less than said transformation component water solubility.

5. The method of claim 4 comprising contacting said substrate with a carbon dioxide source to provide calcium carbonate particles thereon.

6. The method of claim 5 wherein said carbon dioxide source, optionally in the presence of water, is selected from gaseous carbon dioxide, liquid supercritical carbon dioxide and sodium carbonate.

7. The method of claim 6 wherein the presence of water is selected from atmospheric water vapor about said substrate and water applied to said substrate.

8. The method of claim 1 wherein said bone void filler substrate comprises a material selected from calcium salts, collagen, natural mammalian bone, polymers, metals and combinations thereof

9. The method of claim 1 wherein said carbonatable calcium precursor component is provided as an aqueous solution thereof, and application of said carbonatable calcium precursor component is selected from dipping, soaking and spraying said substrate therewith.

10. The method of claim 1 wherein said substrate is applied to a mammalian bone void.

11. A method of using comparative calcium salt solubilities to prepare a bone void filler substrate comprising calcium particles thereon, said method comprising: providing a carbonatable calcium salt precursor component having a water solubility; applying said precursor component to a bone void filler substrate comprising a material selected from calcium salts, collagen, natural mammalian bone, polymers, metals and combinations thereof; and treating said applied precursor component with a transformation component selected from alkali metal hydroxide and alkali metal carbonate components to provide on said substrate a calcium component having a water solubility less than said precursor component water solubility, said calcium component selected from calcium hydroxide and calcium carbonate particles.

12. The method of claim 11 wherein said calcium salt precursor component is selected from calcium chloride, calcium oxide and calcium acetate.

13. The method of claim 11 wherein said transformation component is selected from sodium hydroxide and sodium carbonate.

14. The method of claim 11 wherein said calcium component is calcium hydroxide, and said transformation component is sodium hydroxide, said calcium component having a water solubility less than said transformation component water solubility.

15. The method of claim 14 comprising contacting said substrate with a carbon dioxide source, optionally in the presence of water, said carbon dioxide source selected from gaseous carbon dioxide, liquid supercritical carbon dioxide and sodium carbonate, to provide calcium carbonate particles thereon.

16. The method of claim 15 wherein the presence of water is selected from atmospheric water vapor about said substrate and water applied to said substrate.

17. The method of claim 11 wherein said carbonatable calcium precursor component is provided as an aqueous solution thereof, and application of said carbonatable calcium precursor component is selected from dipping, soaking and spraying said substrate therewith.

18. The method of claim 11 wherein said substrate is applied to a mammalian bone void.

19. A method of using comparative calcium salt solubilities to prepare a bone void filler substrate comprising calcium particles thereon, said method comprising: providing a carbonatable calcium salt precursor component having a water solubility; applying said precursor component to a bone void filler substrate; treating said applied precursor component with a transformation component selected from alkali metal hydroxide components to provide on said substrate a calcium hydroxide component having a water solubility less than said precursor component water solubility; and contacting said substrate with a carbon dioxide source, optionally in the presence of water, to convert at least a portion of said applied carbonatable calcium precursor component to calcium carbonate and provide a coating of discrete, dispersed calcium carbonate particles on said substrate.

20. The method of claim 19 wherein said calcium salt precursor component is selected from calcium chloride, calcium oxide and calcium acetate.

21. The method of claim 19 wherein said transformation component is sodium hydroxide.

22. The method of claim 19 wherein the presence of water is selected from atmospheric water vapor about said substrate and water applied to said substrate.

23. The method of claim 19 wherein said carbonatable calcium precursor component is provided as an aqueous solution thereof, and application of said carbonatable calcium precursor component is selected from dipping, soaking and spraying said substrate therewith.

24. The method of claim 19 wherein said bone void filler substrate comprises a material selected from calcium salts, collagen, natural mammalian bone, polymers, metals and combinations thereof

25. The method of claim 19 wherein said substrate is applied to a mammalian bone void.

Description

EXAMPLES OF THE INVENTION

[0023] The following non-limiting examples and data illustrate various aspects and features relating to the methods/compositions and/or devices of the present invention, including the preparation of various substrates comprising calcium carbonate coatings. In comparison with the prior art, the present methods, compositions and/or devices provide results and data which are surprising, unexpected and contrary thereto. While the utility of this invention is illustrated through the use of several carbonatable calcium precursor components, BVF substrates and reagents which can be used therewith, it will be understood by those skilled in the art that comparable results are obtainable with various other precursor components, BVF substrates and reagents, as are commensurate with the scope of this invention.

Example 1a

[0024] With reference to the equations, below, one approach involves soaking, spraying, or dipping a bone void filler material/substrate in a calcium chloride solution; and soaking dipping, or spraying the calcium chloride wetted substrate with a sodium hydroxide solution to transform the calcium chloride to relatively insoluble calcium hydroxide (and soluble sodium chloride, NaCl). The treated substrate can then be dried (optional) and rinsed with water to remove the NaCl. The final step is to expose the sodium hydroxide treated substrate to a carbon dioxide (CO.sub.2) source to transform the hydroxide into carbonate. Alternatively, such a washing step to remove NaCl can be carried out after carbonate transformation. An advantage is that the carbonate is less soluble than the hydroxide, and such an alternative can provide more carbonate on the bone void filler substrate.

[0025] Calcium hydroxide has a higher solubility than calcium carbonate, but it is still very low (about 1.8 g/1000 ml water). Calcium chloride has a solubility of about 740 g/1000 ml water which is over 400 times greater than that of calcium hydroxide and so provides a better route than direct treatment with calcium hydroxide to cover the substrate surface with a calcium salt. Sodium hydroxide has a very high water solubility (about 1100 g/1000 cc water), and can be used very sparingly to transform a calcium chloride coated substrate to a calcium hydroxide precipitate coating without washing away much of the calcium chloride. The transformation to carbonate is preferably done by exposure to gaseous CO.sub.2, although liquid supercritical CO.sub.2 can be used. The surface of the substrate to be treated is preferably damp, or water vapor can be introduced with the CO.sub.2 to provide a humid conversion atmosphere.

[0026] The end result is a dispersion of nano-sized calcium carbonate crystals over the BVF substrate surface. The surface architecture is unique and cannot be duplicated by depositing a pre-formed calcium carbonate material on the device surface.

Calcium chloride+sodium hydroxide.fwdarw.calcium hydroxide+salt

CaCl.sub.2(aq)+NaOH(aq).fwdarw.Ca(OH).sub.2(s)+2NaCl(aq)

Calcium hydroxide+carbon dioxide.fwdarw.calcium carbonate+water

Ca(OH).sub.2(s)+CO.sub.2(g).fwdarw.CaCO.sub.3(s)+H.sub.2O(aq)

Example 1b

[0027] With reference to the preceding, an alternative route uses an organic calcium salt such as calcium acetate (solubility is about 340 g/1000 ml water), followed by treatment with sodium hydroxide to obtain calcium hydroxide and sodium acetate. Carbonation, as described above, provides the desired calcium carbonate particles/crystals.

Example 2

[0028] Another approach is to cover a BVF substrate surface with calcium acetate (by soaking, dipping, or spraying a calcium acetate solution), then treating the substrate with a sodium carbonate solution (solubility about 340 g/1000 cc water) to transform the calcium acetate to calcium carbonate and soluble sodium acetate that can be rinsed away.

calcium acetate+sodium carbonate.fwdarw.calcium carbonate+sodium acetate

Ca(C.sub.2H.sub.3O.sub.2).sub.2(aq)+Na.sub.2CO.sub.3(aq).fwdarw.CaCO.sub.3(s)+2NaC.sub.2H.sub.3O.sub.2(aq)

Example 3

[0029] Another approach is to cover a BVF substrate surface with calcium chloride (by soaking, dipping, or spraying a calcium chloride solution), then treating the substrate with a sodium carbonate solution to transform the calcium chloride to calcium carbonate along with the formation of soluble sodium chloride that can be rinsed away.

Calcium chloride+sodium carbonate.fwdarw.calcium carbonate+sodium chloride

CaCl.sub.2(aq)+Na.sub.2CO.sub.3(aq).fwdarw.CaCO.sub.3(s)+2NaCl(aq)

Example 4

[0030] Another approach is to transform calcium oxide or another such carbonatable precursor component present in/on a corresponding BVF substrate to calcium carbonate by an aqueous reaction with sodium carbonate. Such a transformation may be a two-step reaction where the calcium oxide is first transformed to calcium hydroxide which then reacts with the sodium carbonate to produce calcium carbonate and sodium hydroxide. The sodium hydroxide is very water soluble and can be rinsed away.

Calcium oxide in water.fwdarw.calcium hydroxide

CaO(s)+H.sub.2O.fwdarw.Ca(OH).sub.2(s)

Calcium hydroxide+sodium carbonate.fwdarw.calcium carbonate+sodium hydroxide

Ca(OH).sub.2(s)+Na.sub.2CO.sub.3(aq).fwdarw.CaCO.sub.3(s)+2NaOH(aq)

Overall Reaction

[0031]
Calcium oxide+sodium carbonate.fwdarw.calcium carbonate+sodium chloride

CaO(aq)+H.sub.2O+Na.sub.2CO.sub.3(aq).fwdarw.CaCO.sub.3(s)+2NaOH(aq)

[0032] While the principles of this invention have been described in conjunction with certain embodiments, it should be understood clearly that these descriptions are provided only by way of example and are not intended to limit, in any way, the scope of this invention. For instance, in conjunction with comparative carbonate salt solubilities, a transformation component such as an alkali metal hydroxide or carbonate can have a solubility greater than that of a carbonatable calcium precursor component. Likewise, methods and resulting compositions of the present invention can be considered in conjunction with various bone implant materials known to those skilled in the art, including but not limited to a mammalian biocompatible anorganic bone mineral matrix produced by removal of organic components. Alternatively, such substrates can be autologous bone from an implant recipient or allograft bone, such as that obtained from a bone bank. Other advantages and features will become apparent from the claims hereinafter, with the scope of such claims determined by reasonable equivalents as would be understood by those skilled in the art and made aware of this invention.