GB2237564A

GB2237564A - Calcium phosphate bone fillers

Info

Publication number: GB2237564A
Application number: GB8924876A
Authority: GB
Inventors: Michael John Atkinson; Peter Hugh Birch; Hideaki Takahiashi; Teruo Haba; Hiroyasu Takeuchi; Masahiro Hirano
Original assignee: Mitsubishi Mining and Cement Co Ltd
Current assignee: Mitsubishi Mining and Cement Co Ltd
Priority date: 1988-07-20
Filing date: 1989-11-03
Publication date: 1991-05-08
Anticipated expiration: 2009-11-03
Also published as: FR2654001A1; DE3937361A1; GB8924876D0; JPH0231749A; FR2654001B1; GB2237564B

Abstract

A filler for filling in defects in bones or regions of osteoporosis contains calcium phosphate with particles of cylindrical or polygonal column shape. A cross-sectional contour is substantially the same along the length of the filler particles and the ratio of length to diameter of the cross-section thereof is in the range from 0.1 to 10. Phosphate is e.g. hydroxyapatite, calcium pyrophosphate, tricalcium phosphate etc.

Description

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TITLE OF THE INVENTION

Filler For Filling In Defect Of Bone And Region Of Osteoporosis BACKGROUND OF THE INVENTION

This invention relates to a filler for filling in a defect of bone and a region of osteoporosis and, more particularly, to such a filler containing a calcium phosphate compound.

Osteoporosis is a syndrome in which the quantity of bone is reduced from various reasons. Human bone completes its growth at the age of about 20, its length and width becoming maximum at this age and its quantity becoming maximum at the age of 20 to 30. However, as the middle to advanced age is approached, the bone becomes thin and the quantity of bone is reduced, even with healthy persons, although the size of bone remains substantially unchanged. Above all, the quantity of bone is reduced rapidly with post-menopausal women and with men and women at the age of 65 or more. In addition, the quantity of bone may be reduced by diseases of internal secretion, stomach. intestines, liver or kidney or as a result of administration of medicines, such as gluco-corticoid, to cause osteoporosis. When one is attacked by osteoporosis, bone fracture may be caused easily due to the lowered mechanical strength of bone. Examples of typical bone fracture caused by osteoporosis include compression fracture of spine, 1 1 femoral neck fracture and radial distal portion fracture.

Up to now, no therapeutic methods have been found for osteoporosis except administration of medicines, such as female sex hormones, active type vitamin D or calcitonin. However, it has not been possible with the therapy by medicines to reposition the centrum of the vertebra which has been compressed or turned into a wedge form under compression fracture or to positively increase the quantity of bone.

On the other hand-, clacium phosphate compounds are known to be capable of forming bone and useful as the filler for filling in defect or hollow portions of bone. However, when the compounds are applied to the therapy of osteoporosis, it is necessary to introduce a predetermined amount of the calcium phosphate compounds into a particular site at which the quantity of bone is decreased. Above all, in case of a deeper operation site, considerable difficulties are experienced in introducing the filler. Although these difficulties may be overcome with the use of a suitable dispenser, the known types of the filler composed of the calcium phosphate compounds suffer from insufficient fluidity and cannot be injected easily through the dispenser. In a case where the filler is applied to the therapy of osteoporosis, it must be expected that the filler need remain affixed for a prolonged time period in the site at which the quantity of bone has been reduced, to thereby 2 1 1 increase the amount of bone.

There has been proposed in, for example, Japanese Laid-open Patent Application No.26856211987, a filler for osteoporosis containing particles of calcium phosphate compounds with each particle having the ratio of maximum axis to minimum axis in the range of from 1:1 to 1:5 and the angle of repose in the range of from 100 to 450. Although the problem of insufficient fluidity of the particles of calcium phosphate compounds may be removed to some extent with this prior-art filler, filling cannot be performed smoothly into a deeper site of lesion. Besides, due to the random particle shape, it may occur that filling cannot be performed when the filler is extruded from the dispenser in one direction. Furthermore, sufficient bone forming capacities may not be achieved when the calcium phosphate compounds are used in combination with other substances, such as bone morphogenetic protein or fibrin. SUMMARY OF THE INVENTION

It is a principal object of the present invention to provide a filler for filling in a defect of bone and a region of osteoporosis which is excellent in fluidity and which can be poured directly or applied by a dispenser easily into the site of lesion.

It is another object of the present invention to provide a filler for filling in a defect ofbone and a region of osteoporosis which can be introduced into deeper 3 sites in the living body with the use of a dispenser.

It is a further object of the present invention to provide a filler for filling in a defect of bone and a region of osteoporosis which is excellent in fluidity and which allows to reduce the area of resection or incision when the filler is filled in with the use of a dispenser.

It is a further object of the present invention to provide a filler for filling in a defect of bone and a region of osteoporosis which, despite its improved fluidity, may remain affixed to the site for a long time period after it is applied thereto to permit the quantity of bone to be increased.

The above and other objects, features and advantages of the present invention will become more apparent from the following description.

According to the present invention, there is provided a filler for filling in a defect of bone and a region of osteoporosis, the filler containing a calcium phosphate compound and having a shape selected from the group consisting of a cylindrical shape and a polygonal column shape, with a cross-sectional shape being substantially the same along the length of the filler and with a ratio of length to diameter of the cross- section thereof being in the range from 0.1 to 10. BRIEF DESCRIPTION OF THE DRAWINGS

Fig.1 is a diagrammatic perspective view showing a 4 cylindrical filler according to the present invention.

Fig.2 is a diagrammatic perspective view showing a polygonal column filler according to the present invention. PREFERRED EMBODIMENTS OF THE INVENTION The present invention will be explained in more detail hereinbelow.

The calcium phosphate compounds employed in the present invention include tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, oxyapatite, calcium pyrophosphate, fluoroapatite and.mixtures thereof. Particularly preferred is one or more calcium phosphate compounds selected from the group consisitng of tricalcium phosphate, hydroxyapatite, fluoroapatite and tetracalcium phosphate which permit a higher rate of formation of new bone. Most preferred is hydroxyapatite, above all, hydroxyapatite sintered at 5000C or higher and more desirably at 7000C or higher, since it provides for the highest rate of formation of new bone and exhibits lower solubility so that it becomes affixed for a prolonged time period to the site of the decreased bone quantity to perform its osteogenetic functions. Although there is no limitation to the upper limit temperature of heat treatment, it should be lower than the decomposition temperature of hydroxyapatite which otherwise starts to be decomposed. The calcium phosphate compounds employed in the present invention may be produced from natural bone or synthesized 1 1 artificially by a wet process, a dry process or a hydrothermal process, in a manner known per se.

The filler employed in the present invention should have the shape of a cylinder 10 as shown in Fig.1 or a polygonal column 20 as shown in Fig.2. The cross-sectional profile of the column need not be coincident with the tubular profile of a dispenser, as long as the dispensing operation is not obstructed although that is preferred. The cylindrical or polygonal column shape of the filler may be selected suitably depending on whether the cross-sectional profile of the holder of the dispenser and the dispensing tube has a cylindrical shape or a polygonal column shape.

The cross-sectional diameter of the filler employed in the present invention is preferably 0.2 to 10 mm and more preferably 0.2 to 5 mm. If the cross-sectional diameter exceeds 10 mm, formation of new bone around the filler is retarded, whereas, if the cross-sectional diameter is less than 0.2 mm, the filler is carried away by the blood and the like, without becoming affixed to the filled portion so that sufficient osteogenetic properties cannot be expected. In view of convenience in the dispensing operation, the cross-sectional shape or profile of the filler of calcium phosphate compounds of the present invention should be substantially the same along the length thereof. In addition, in order for the filler to be introduced into deeper sites of defect of bone or regions of osteoporosis, 6 A a i the ratio of the length to the cross-sectional diameter of the filler should be in the range from 0.1 to 10.

The cylindrical or polygonal column filler of the calcium phosphate compounds employed in the present invention may prefarably be porous or of densely sintered texture. It may also be used in combination with substances capable of further promoting its osteogenetic properties, such as bone morphogenetic protein and/or fibrin.

The filler of the present invention is in the form of particles of calcium phosphate compounds. When the compound of natural origin or the compound produced by the dry process is employed, such particles may be produced by pulverizing the calcium phosphate compounds, adding a solution of a binder, such as polyvinyl alcohol or methyl cellulose, to the thus produced powders of the calcium phosphate compounds, to thereby produce a moderately plasticized mixture, extruding the mixture by an extruder, such as a suitable twin-axis granulator, to form the shape of a desired cylinder or polygonal column, and sintering the thus molded products at a sintering temperature of'700 to 12000C. When the compound produced by the wet process or the hydrothermal process is employed, the particles may be produced by drying a slurry of the calcium phosphate compound in situ and crushing the dried mass. Alternatively, the particles may be obtained by pulverizing the calcium phosphate compounds, adding the aforementioned 7 4 binder solution to the thus produced powders to produce a moderately plasticized mixture, forming the plasticized mixture into the shape of a cylinder or a polygonal column and sintering the thus molded particulate products.

The cylindrical or polygonal column filler of the calcium phosphate compounds employed in the present invention may be contained directly in a suitable dispenser. However, for providing a more facilitated dispensing operation and avoiding the necessity for repeated insertion and removal of the dispenser into or from a defect of bone or a region of osteoporosis, to thereby reduce the time for surgical operation, for example the filler is preliminarily inserted and stored in a suitable holder and the holder is preferably inserted into the dispenser. For safety of operation, such a holder is preferably formed of a sterilizable material, such as polypropylene or polyethylene. EXAMPLES OF THE INVENTION The present invention will be explained with reference to a specific example. It is to be understood that the example is given only for the sake of illustration and not in the limiting sense. Example 1 Dried hydroxyapatite produced by the wet process was pulverized to a mean particle size of 0.5 to 1.0 mm after addition of a polyvinyl alcohol solution thereto.

8 tt il Then, the powders thus produced were molded to particles each in the form of a cylinder with the diameter of the particle surface of 2 mm and the length of 3 mm with the aid of a twin-axis granulator, not shown, and sintered at 9500C to produce a filler of hydroxyapatite particles each in the form of a cylinder having a uniform or similar cross-sectional profile. The filler produced was charged into a filler dispenser and introduced into a defect of bone and a ragion of osteoporosis. The filler could be introduced smoothly into the sites of lesion and the results of therapy were satisfactory. Compartative Example 1 A filler of hydroxyapatite particles was prepared in the same way as in Example 1 except that the cross-sectional profile of the particles in the diametral direction was substantially non-uinform and variable and the long axis diameter was selected to be 20 mm. Although it was attempted to introduce the produced filler into the site of lesion, using a filler dispenser in the same way as in Example 1, it was found impossible to introduce the filler in this manner because of clogging.

The filler calcium phosphate compounds according to the present invention for filling in a defect of bone and a region of osteoporosis, which is in the form of cylindrical or polygonal column, can be introduced easily in a prescribed amount to a desired site of lesion to display an 9 effect in therapy of osteoporosis.which it was thought to be difficult to remedy completely. Also the filler of the present invention may be applied easily to a deeper site in the living body, while the area of incision necessary for operation may be reduced significantly.

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Claims

CLAIMS:

1. A bone filler containing a calcium phosphate compound and being shaped as a cylinder or a polygonal column with a substantially uniform cross-sectional shape and with a ratio of length to maximum cross sectional width being from 0.1 to 10.

2. A bone filler according to claim 1, wherein the calcium phosphate compound is tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, oxyapatite, calcium pyrophosphate, fluoroapatite or a mixture thereof

3. A bone filler according to claim 1 or claim 2, having a maximum crosssectional width of from 0.2 to 10 film.

4. A bone filler according to any preceding claim, further containing an additive comprising bone morphogenetic protein, fibrin or a mixture thereof.

5. A bone filler according substantially as described herein.

to claim 1 ' Published 1991 at The Patent Office. State House. 66/71 High Holborn. London WCIR47P. Further copies maybe obtained from Sales Branch. Unit

6. Nine Mile Point Cwmilclinfach. Cross Keys, Newport. NPI 714Z. Printed by Multiplex techniques lid, St Mary Cray. Kent.