Compositions: coating or plastic – Coating or plastic compositions – Inorganic settable ingredient containing
Reexamination Certificate
2002-03-04
2004-02-17
Wood, Elizabeth D. (Department: 1755)
Compositions: coating or plastic
Coating or plastic compositions
Inorganic settable ingredient containing
C106S696000, C106S691000, C106S035000, C106S690000
Reexamination Certificate
active
06692563
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to a magnesium ammonium phosphate cement preparation, a process for its production and an associated use.
BACKGROUND OF THE INVENTION
This invention relates in particular to a biologically degradable cement, which consists in its main phase of magnesium ammonium phosphates and nanoapatites after hardening and thus at the same time has a high strength.
The material may be used as bone replacement, for bone augmentation and for bone regeneration.
It may serve as excipient for pharmaceutical or biological active ingredients.
The most important mineral constituents in human bone and tooth enamel are calcium and phosphate. However, considerable quantities of sodium, magnesium and carbonate are also present.
It is known from precipitation studies of synthetic systems that sodium ions and carbonate ions may be incorporated very easily into calcium phosphate precipitates resulting in a molecular structure similar to apatite.
However, magnesium has a strong tendency to precipitate in a different structure not similar to apatite.
Calcium phosphate precipitated physiologically as bone and dentine is nanocrystalline. It cannot be seen from an X-ray diffractogram, due to line broadening, whether it is apatite or other structures.
Some scientists are of the opinion that so much magnesium occurs in bone and dentine that this cannot all be taken up in the apatite structure. Therefore, a mixed form of the mineral of nanoapatite and nanodolomite or nanostruvite is assumed here.
Calcium phosphates are not only biocompatible but are recognised by the living cell as belonging-to-the-body. Therefore, there are many biomaterials and medical products which consist partly of calcium phosphate.
Calcium phosphate ceramics have been on the market since about 1970, partly in the form of prefabricated blocks or as granules.
Implantations of these materials in bone structures are predominantly successful. The biggest disadvantage of these systems is that the blocks have to be prefabricated and the granules drift away (flood out) from the side of the implantation. This often leads to failure of such implantations.
Calcium phosphate ceramics are most successful when they consist of hydroxyl-apatite (HA) or of beta-tertiary calcium phosphate (&bgr;-TCP, a whitlockite-like structure) or when the calcium phosphate ceramics consist of both, HA and &bgr;-TCP in variable ratios. HA is virtually non-resorbable from bone implantations, whereas &bgr;-TCP is slowly resorbed and replaced by new bone.
It is therefore possible to influence the degree of resorption of calcium phosphate ceramic by changing the &bgr;-TCP/HA ratio.
It is likewise possible to admix other resorbable materials, such as: monetite CaHPO
4
, brushite CaHPO
4
-2H
2
O, calcite CaCO
3
and dolomite CaMg(CO
3
)
2
.
Since 1985 attempts have been made to develop calcium phosphate cements in order to avoid the disadvantages of prefabricated or granular-like calcium phosphate ceramics (W. E. Brown and L. C. Chow, “A new calcium phosphate, water-setting cement”, Cem. Res. Prog. 1986 352-379 (1987)).
This includes a brushite cement not yet commercially available having a Ca/P molar ratio of the precipitated phase of 1.00. This phase is not nanocrystalline but microcrystalline. All the other calcium phosphate cements developed hitherto have a nanocrystalline precipitation structure and a Ca/P molar ratio of >=1.5, which may be further increased by addition of carbonate. These materials are known under U.S. Pat. No. 5,605,713; European application 0 835 668; World 96/14265, and some of these materials are already on the market.
There are contradictory reports regarding the resorbability of these materials after implantations in bone and soft tissue.
In each case, calcium phosphate cements based on hydroxylapatite (HA) which are not resorbable (HA ceramics see above) and calcium phosphate cements based on deficient calcium hydroxylapatites (CDHA, calcium deficient hydroxylapatites) which are good osteotransductively, are differentiated.
This means for the last-mentioned case, that they may be resorbed by osteoclasts and may be replaced by new bone tissue from osteoblasts.
Resorption of these cements depends crucially on the local bone transformation mechanisms.
Today, most surgeons require a calcium phosphate cement, in which initially a mechanically supporting mode of action is brought to bear, but the final resorption lags behind independently of the local transformation mechanisms of the bone, that is that the material is completely degraded. In addition, it is known in orthopaedics that vital bone only remains where it is required from the biomechanical point of view. This is known as the so-called Wolff's Law. Consequently, if a calcium phosphate cement introduced into a bone defect has a higher compressive strength than the bone surrounding it and this high compressive strength remains unchanged, this leads to degradation of bone tissue lying around the implant (here calcium phosphate cement).
In order to fulfil this requirement, even if only partly, some manufacturers have admixed substances into their CDHA cements which are similar to nanoapatite, which are passively resorbed by the bodily fluids due to the concentration gradients, such as for example monetite (CaHPO
4
) or calcite (CaCO
3
) as known from European 0 543 765.
However, this only partly solves the problem. A cement is also required which can be resorbed completely passively and in which the resorption front and the deposition front are in direct contact.
Gypsum for example does not fulfil this requirement. Gypsum is resorbed so rapidly that there is always a gaping hole between the resorption front and the deposition front and these materials do not have adequate supporting function due to their low resistance to pressure. Such materials are disclosed, for example under U.S. Pat. No. 5,281,265.
For these reasons, it is desirable to provide a bone replacement material, which initially takes over the lost supporting function of the bone with high resistance to pressure, but then successively decreases in resistance to pressure, as a result of which the endogenous bone transformation processes (remodelling) are stimulated and hence more rapid osteoneogenesis and hence also active resorption of the bone replacement material is introduced. This may also be achieved by incorporating a slightly soluble substance, for example into a hardening cement paste. Because bone grows well into macroporous structures, it is advantageous to admix granular or pellet-like, solubilising substances consisting of, for example sugars, salts (for example NaCl) or gypsum (CaSO
4
) into the cement paste. They are then leached out very rapidly in the body from the hardened cement structure and a porous sponge-like structure remains. Production of a porous (finished) cement outside the body is also conceivable.
In order to be able to use a cement for dental applications, such as for example filling and sealing of small dentine channels, filling of tooth cavities after vital extirpation, utilising such a cement as sub-filling material in endodontology, such a material may not shrink to prevent passage of bacteria. Even a material having low-grade expandable properties would be desirable.
It is the object of the invention to provide a cement preparation, with which the disadvantages of the state of the art are avoided.
SUMMARY OF THE INVENTION
The present invention provides a magnesium ammonium phosphate cement preparation, comprising: a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<Ca/P<1.50 and 0<Mg/P<0.50; an ammonium salt; and water and/or an aqueous solution.
In one embodiment, the present invention provides a magnesium ammonium phosphate cement preparation, comprising: a powder mixture, consisting of (&agr;-TCP, &bgr;-TCP, MgHPO
4
×3H
2
O, KH
2
PO
4
and Na
2
HPO
4
; an ammonium salt; and water and/or an aqueous solution.
In another embodimen
Kyphon Inc.
Townsend and Townsend / and Crew LLP
Wood Elizabeth D.
LandOfFree
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