WO1993007912A1

WO1993007912A1 - Bioimplant elements

Info

Publication number: WO1993007912A1
Application number: PCT/US1992/008641
Authority: WO
Inventors: Masaki Ogawa
Original assignee: Sherwood Medical Company
Priority date: 1991-10-15
Filing date: 1992-10-15
Publication date: 1993-04-29
Also published as: AU2779792A; JPH05103826A

Abstract

A bioimplant element made of an organic polymer base material is coated with hydroxyapatite similar to bone in structure and composition. The organic polymer base material contains a sulfonic group and/or a carboxyl group, which is coated with a durable layer of hydroxyapatite about 3-100 νm, or preferably about 10-60 νm, thick using a process for depositing the hydroxyapatite that preferably includes a first water solution of hydroxyapatite containing glass powder covering the portion of the bioimplant element to be implanted, and a second water solution of hydroxyapatite having no glass powder.

Description

Bioimplant Elements

Technical Field

The present invention concerns bioimplant elements to be used for life support or treatment in case of illness or 5 accidents. That is, it is related to an element which is located at the connection between inside and outside a body to externally provide liquid medicine through a catheter, etc. , a bioimplant element which is totally implanted in vivo to provide an injection port for injecting medicine 10 deep inside the body, or a bioimplant element which is to replace or supplement damaged parts of hard structures such as bones.

Background Art

Recent progress of research on implant materials has

15 been remarkable. New materials have been developed not only for artificial organs but also for plastic surgery and artificial teeth, etc. Among these materials, hydroxyapatite which is known for its high biological activity and its unique property to integrate with bones has

20 attracted attention. Consequently, various inventions concerning implant materials which are based on this material have been published. In Tokkai Hei 3 (1991) - 186272, an element to be used in a bone was disclosed, which is obtained by coating ceramics such as alumina and

25 zirconia, or pure titanium or titanium alloys with a calcium phosphate material such as hydroxyapatite.

In Tokko Hei 2 (1990) - 13580, a technique was disclosed, in which bioterminals made of sintered hydroxyapatite are used at the connection between inside and rfi

30 outside of a body for externally picking up information in vivo. In addition, in Jikko Hei 3 (1991) - 19884, a technique concerning bioterminals of hydroxyapatite made from animal bones was also published. In Tokkai Hei 3 (1991) - 32676, a technique concerning compounds of zirconia or alumina and hydroxyapatite was published. It is to increase the strength of hydroxyapatite which had prevented its practical use. Various methods for obtaining hydroxyapatite were also published. Among them are: the sintering process in Tokko Hei 2 (1990) - 13580; the plasma spray process for metallic implant materials in Tokko Sho 58 (1983) - 50737; the plasma jet process for ceramic core materials in Tokko Sho 59 (1984) 46911, Tokkai Sho 62 (1987) - 34539, Tokkai Sho 62

(1987) - 57548, Tokkai Sho 63 (1988) - 46165 and others; the sputtering process in Tokkai Sho 58 (1983) - 109049; the flame jet process in the Proceedings of the Japan Ceramics Society 1988 1st Fall Symposium, Preprint, pp. 401-402; and the glass frit baking process in the Proceedings of the 9th Conference of Biomaterials Society (Preprint, 1987, p.6). In addition, the electrophoresis process was published in the Japan Ceramics Society, 1988, pp. 417-418.

The processes to precipitate hydroxyapatite from an artificial body fluid composed of the same ion type and concentration as human blood plasma were published in Tokko Sho 61 (1986) - 10939, Tokko Hei 1 (1989) - 54290 and Tokkai Hei 2 (1990) - 255515.

As described above, various bioimplant elements and their preparation processes have been published.

Nevertheless, there remain many problems to be resolved. Among them are as follows.

(A) The plasma jet process requires sophisticated and expensive equipment, does not readily produce fine coating and forms coating of apatite which is different from the apatite in the biological body because the source material, -hydroxyapatite, is once melted at high temperatures.

(B) The sputtering process requires sophisticated and expensive equipment and forms coating of apatite which is different from the apatite in vivo because the source material, hydroxyapatite, is once melted at high temperatures.

(C) The sintering and glass frit processes require heat treatments at temperatures 850°C or above and therefore can be applied only to base materials with high heat resistance and form coating of apatite which is different from the apatite in vivo because the source material, hydroxyapatite, once receives treatment at high temperatures. Also, terminals made from the sintered material are subjected to severe restrictions on the structure and shape because of the low strength of hydroxyapatite.

(D) The electrophoresis process can be applied only to metallic base materials with good electrical conductivity because it uses the base material itself as electrodes and also forms coating of apatite which is different from the apatite in vivo because it uses crystal apatite as the source material.

(E) The precipitation process from an artificial body fluid has a weakness that no base materials other than CaO/Si0₂ base glass, which provide a good bonding with hydroxy apatite generated, have been found.

(F) As a method to resolve some of the problems described above, it has been known that epoch-making implant elements can be obtained by coating organic polymers with hydroxyapatite having similar composition to that in living body. However, because the difficulties to obtain sufficient bonding strength between hydroxyapatite and organic polymers have not been resolved, the method could not be implemented in practice.

Disclosure of Invention.

The present invention is the result of the concentrated efforts by its inventor to resolve the various problems described above, more specifically, the problem in (F) . It is intended to provide bioimplant elements of organic polymer base which have excellent biological compatibility, sufficient strength and design flexibility.

A bioimplant element pertaining to the present invention consists of the base material which is made of a organic polymer containing sulfonic group or/and carboxyl group and the bone-like coating of hydroxyapatite which is formed on the surface of the said base material and CaO/Si0₂ base glass powder in the practically saturated or supersaturated water solution of hydroxyapatite. The preferred thickness of such hydroxyapatite coating is in the range of 3-100μm and the organic polymer containing sulfonic group is polyethersulfon, polysulfon or polyallylsulfon, or/and is a compound containing organic polymers selected from among them.

The preferred organic polymer containing carboxyl group is a polymer which is obtained through copolymerization of ole in and carboxylic acid containing vinyl group and then is bridged with metallic ions, or/and is a compound containing this organic polymer in which the preferred olefin is ethylene and the preferred carboxylic acid containing vinyl group is methacrylic acid.

For the surface of the base material, nonspecular surface with low glossiness is preferred. A part of phosphate group or hydroxyl group in hydroxyapatite may be substituted by carbonic group. It is desirable that more than 80% of the Ca0/Siθ₂ base glass powder has grain diameters in the range of 100 - 600μm. The method of the present invention described above stems from the discovery by the inventor that bioimplant elements with excellent biological compatibility, sufficient strength and design flexibility can be obtained by using an organic polymer containing sulfonic group or/and carboxyl group as the base material along with the process to generate hydroxyapatite from a practically saturated or supersaturated water solution of hydroxyapatite, preferably from an artificial body fluid with the same ion composition and concentration as the human blood plasma. That is, the gist of the present is the discovery that the organic polymers containing sulfonic group or/and carboxyl group are among the desired organic polymers which bond strongly with hydroxyapatite. Therefore, implant elements obtained by coating hydroxyapatite over the layer of an organic polymer containing sulfonic group or/and carboxyl group which is formed on the surface of other base material fall within the claim of the present invention.

Brief Description of Drawings.

Figure 1 shows a top view of a bioimplant element on which hydroxyapatite may be coated according to the present invention.

Figure 2 shows a sectional side view of the bioimplant element shown in Figure 1.

Figure 3 shows a right side view of the bioimplant element shown in Figure 2. Figure 4 shows a schematic representation of one step in the preferred process for hydroxyapatite coating according to the present invention.

Figure 5 shows a schematic representation of another step in the preferred process for hydroxyapatite coating according to the present invention.

Figure 6 shows an implant device assembled using the bioimplant element shown in Figures 1-3 according to the present invention.

Figure 7 is an illustration of the bioimplant device shown in Figure 6 implanted in a living body.

Best Modes for Carrying Out the Invention.

In the present invention, an organic polymer containing sulfonic group or/and carboxyl group is required for the base material of bioimplant elements in order that it provide sufficient bonding strength with hydroxyapatite for practical use. However, since the function of the organic polymer is to improve the bonding with hydroxyapatite, it is only necessary for such polymer to have sulfonic or carboxyl group on its surface. For example, when polypropylene selected as an organic polymer receives plasma treatment for 3 minutes at 0.1 Torr, 8 cc/minute and 150 Ma using carbon monoxide as reagent, carboxyl group is introduced into about 7% of carbon atoms on the surface and yields sufficient bonding strength with hydroxyapatite.

Polyestersulfon, polysulfon, ionomer, carboxylic acid modified polyolefin (e.g., brand name: Mitsui Lonply*) and others are among organic polymers containing sulfonic group or carboxyl group. However, other polymers may be used as long as sulfonic group or carboxyl group is present on the surface in contact with hydroxyapatite.

The desirable thickness of hydroxyapatite coating is in the range of 3 - 100 μm. When the thickness of coating is below 3μm it may possibly be eroded and eliminated while implanted in a living body. When it exceeds 100 μm, strains caused by the differences in expansion coef icients between the base material and hydroxyapatite against temperature and humidity changes tend to be excessive and as a consequence the hydroxyapatite coating becomes more susceptible to cracking and subsequent separation which develops from such cracks. In addition, for example, the increased time to formation of such thick coating of hydroxyapatite inflates the manufacturing costs, making the thicker coating impracticable. The preferred base material with the highest bonding strength with hydroxyapatite is the ionomer which is obtained by bridging ethylene-methacrylic acid copolymer with metallic ions (e.g., brand name: Hy iIan*/Mitsui DuPont Polychemical Co.). The preferable hydroxyapatite is that with a part of its phosphate or hydroxyl group substituted by carbonic group, because in such form it is closer to hydroxyapatite in a living body and has better biological compatibility.

The CaO/Si0₂ base glass powder refers to the glass powder which contains CaO and Si0₂ in the following ranges: CaO ...... 20 - 60 mol%

Si0₂ 40 - 80 mol% and more than 70 mol% CaO and Si0₂ combined and more than 80% of powder having grain diameters in the range of 100- 600μm. The composition of CaO/ Si0₂ base glass is published in Tokkai Hei 2 (1990) - 25515.

The preferred grain diameter of the glass powder is in the range of 100-600μm. If it is below 100 μm, it is too small for sufficient amount of saturated or supersaturated water solution of hydroxyapatite to be supplied between glass grains and the base material and the growth of the hydroxyapatite coating does not occur or is too slow to be practicable. If, on the other hand, it exceeds 600μm, sufficient nuclei for growth are not formed on the surface of the base material and therefore the growth is too slow or the surface becomes nonuniform, making it unpracticable.

It is desirable for more than 80% of the glass powder to have grain diameters in the range of 100 - 600μm. If it is below 80%, the increase in grains with diameters not in the range of 100 - 600μm retards the growth of hydroxyapatite or totally prevents its growth.

The CaO/Si0₂ base glass used in the present invention was prepared from the compound of glass materials shown in the left column below. The composition of the glass obtained is shown in the right column. <Compound of Glass Materials> <Composition of Glass> mol%

CaO 49.87

Si0₂ 35.46

P₂0_s 7.153 MgO 7.111

CaF- 0.399 The uniformly mixed fine powder obtained from the compound of glass materials shown above using a mortar was melted for 2 hours at 145°C in a platinum crucible. It was rapidly quenched on a steel plate and then milled in a ballmill. This was then sifted to prepare several glass powders classified in Table I.

Table I

The practically saturated or supersaturated water solutions of hydroxyapatite. Solution(1) and Solution(2) , with the compositions shown below were prepared and their pH at 36.5°C were adjusted to be 7.4 by controlling the content of hydrochloric acid. Tri(hydroxylmethyl)aminomethane in the compound was used as the pH buffer.

Compositions in lϋ Water Solutions

Solution(1) Solution(2)

NaCl 7.996 g 11.994 g

NaHC0₃ 0.350 g 0.535 g C1 0.224 g 0.336 g

MgCl₂-6H₂0 0.305 g 0.458 g

CaCl₂ 0.278 g 0.417 g

Na₂S0₄ 0.071 g 0.107 8

1NHC1 approx. 45 ml approx. 68 ml

Tri(hydroxylmethyl) aminomethane 6.057 g 8.086 g

The bioimplant elements in the present invention is explained using Figure l, which shows the configuration of the implant element called a skin button, and Figures 2 and 3, which are schematics of the process of hydroxyapatite coating on the surface of the implant element. In Figure 1, 11 is the implant element made of polyethersulfon (ICI Co. brand name: PES4100G) , 1 is the top adapter, 2 is the bottom adapter which is connected .to the flange 3 of the top adapter 1 and connects the vents 8 and 8a via the vent 8b. In Figures 2 and 3, 4 and 4a is the vessel, 5 is the glass powder described above, 6 is Solution(1) , and 7 is Solution(2) .

Implant a part of the implant element 11 shown in Figure 1 in the glass powder 5 of Glass D and immersed it in Solution(1) 6. After leaving it in a thermostatic chamber at 36.5°C for 1 week, take out the implant element 11 and immerse it in Solution(2) 7. After leaving it in the thermostatic chamber at 36.5°C for 1 week, take out the implant element 11 and clean it with distilled water and dry it at 60°C. Through this procedure, hydroxyapatite coating (not shown in the figure) of the present invention similar to bones is formed on the surface of the implant element 11 which is in contact with the glass powder 5, as shown in Figure 1.

A total of 22 samples consisting of 9 embodiments and 13 references were prepared through the procedure described above. Two elements were prepared for each sample condition: one was used for breaking test and the other was implanted in a grown dog to evaluate biological compatibility. The following three characteristics, A - C, were evaluated.

A. Measurements of Hydroxyapatite Coating

A pat of the flange of the said implant element was cut off and a slit was made on undamaged part of the coating with a knife. Then the thickness of hydroxyapatite at the cut by a scanning electron microscope tilting the sample by 50° to the direction of electron beam. The results obtained after calibrating for this angle are presented in the following tables.

B. Bonding Strength between Base material and Hydroxyapatite Coating A part of the flange of the said implant element was cut off and a cellophane tape (adhesive tape) was put on undamaged part of coating. The bonding strength was evaluated by observing whether separation of the hydroxyapatite coating occurs when the tape was peeled off. C. Biological Compatibility

The implant device shown in Figure 4 was assembled using the said implant element which was not used in the breaking test. The device sterilized with ethylene oxide gas was implanted in the breast of a grown dog, as shown in Figure 5. The biological compatibility was evaluated observing the conditions after 1 day, 3 days, 1 week, 2 weeks, 3 weeks and 1 month. To facilitate the sensitive evaluation of the biological compatibility, the implant device was partially implanted in the body. The evaluation was made by observing the conditions at the interface between the skin surface and the implant device. In Figures 4 and 5, the upper tube 12 is connected to the vent 8 of the implant element 11 and the lower tube 13 is connected to the vent 8a by the tightening thread 14. At the end of the upper tube 12, a Luer adapter 17 and an intermittent infusion plug 18 are attached and fixed with a clamp 19. The bottom adapter 2 including the flange 3 of the implant element 11 is implanted under the skin, namely inside the body and the end of the lower tube 13 is connected to the inserted catheter 16 via the connector 15 and extended to the prescribed organ (not shown in the figure) in the body.

In the following, the results of the evaluation are explained for the selected embodiments: Embodiments 1 and 2, Embodiment 3, Embodiments 4 - 9, and Embodiment 10, in comparison with the reference samples. Embodiments 1 & 2:

In Embodiments 1 & 2, it is demonstrated that the implant elements based on the present invention can be bonded to hydroxyapatite coating with more than adequate strength for practical use and have excellent biological compatibility. In References 1 - 10, the base materials used are, respectively, polycarbonate, polymethyl methacrylate, polyethylene, polystyrene, polypropylene. Teflon, ABS resin, polyvinyl chloride resin, polyurethane resin and nylon. The results are presented in Table 2 and continued to Table 3.

Polymethyl methacrylate in Reference 2 was prepared in the same conditions as those in Table 7 of Embodiments 2 in Tokkai Hei 2 (1990) - 25515, and polyethylene in Reference 3 was prepared in the same conditions as those in Table 7 of Embodiments 2 in Tokkai Hei 2 (1990) - 25515.

The surface of all base materials were made rough using #150 sand paper.

Table II

Brand names and manufacturers of the base materials in Tables 2 & 3 are listed below.

Brand Name Manufacturer PES4100G ICI Japan Himillan 1706 Mitsui Polychemical Novalex 7022A Mitsubishi Kasei Delpet 6ON Asahi Kasei Brand Name (cont) Manufacturer (cont) Neozex 45150 Mitsui Sekiyu Kagaku Dialex HF-77 Mitsubishi Monsanto Noblen EBG Mitsui Tohatsu Teflon PTFE

(polytetrafluoroethylene)

Styrac 101 Asahi Xasei SR-1158 Riken Vinyl Kogyo (medical grade)

EG65D Ther edics Co. Diamid 1901 Huhls Co.

The downgrowth describing the biological compatibility in Tables 2 & 3 refers to the phenomenon that the skin sinks near the interface with the implant element. The biological compatibility is judged to be better when there is less downgrowth.

When the biological compatibility is good, the resistance of the organism against external infectants does not decrease and therefore the infection does not develop readily. It is regarded as an epoch-making result that no infection occurred for the implant elements in these embodiments of the present invention even after disinfection was discontinued.

Embodiment 3:

In this embodiment, it is demonstrated that it is desirable for more than 80% of the glass powder to have grain diameters in the range of 100-600μm. Embodiment 3 and References 12 and 13 were compared. The results are presented in Table 4.

Polyethersulfon was used for the base material and, except for changing the glass powder, the conditions were the same as those in Embodiment 1. Table IV

The result in Table 4 demonstrates that the coating of hydroxyapatite is hardly formed when the volumetric proportion of glass powder having grain diameters in the range of 100-600μm is less than 75% and that the proportion therefore is necessarily more than 80%.

Embodiments 4 - 9:

Embodiments 4 - 9 were prepared by changing the duration of immersion of the implant elements in Solution(2) to obtain different thicknesses of hydroxyapatite coating. Other conditions were the same as those in Embodiment 1. The results of evaluation are presented in Table 5.

The results for these embodiments presented in Table 5 indicate that the preferred thickness of hydroxyapatite coating in the present invention is in the range of 3-100 μm, more preferably, 10-60μm.

Table V

After 3 weeks, it was observed that hydroxyapatite coating had disappeared from the sample of embodiment 4.

After 1 month, it was observed that hydroxyapatite coating had partially disappeared from the sample of Embodiment 9.

Embodiment 10 :

In Embodiment 10 , the implant base material made of polysulfon (AMOCO Japan: Udel P1700) in the form of a circular cylinder with a radius 8 mm and a height 15 mm was coated with 14μm thick hydroxyapatite in a manner similar to that in Embodiment 1.

This element was implanted in a thighbone of a rabbit. It was removed after 10 weeks and the bonding conditions between the implant element and the bone were examined. It was observed that the living tissue was totally united with the implant element. This material, with its bonding strength exceeding 1100 kg/cm² and elongation to rupture about 90%, is far superior to other implant materials such as bioglass and sintered hydroxyapatite, and can provide light weight implant elements with excellent biological compatibility.

The implant elements of the present invention were described above using various embodiments. It has been well known that hydroxyapatite exhibits excellent biological compatibility. Nevertheless, because of its low strength, its use for implant elements in the form of the sintered hydroxyapatite has been limited to the parts not subjected to large loads. While metallic base materials or processes of coating ceramics have been developed to overcome this difficulty, they have not been used for general purpose implant elements because the materials are expensive or have poor moldability. Naturally it is ideal to coat organic polymers, which have much better moldability and are less expensive than other materials, with hydroxyapatite. However, this has not been practicable because the bonding strength with hydroxyapatite has not been sufficient. In the embodiments, it was demonstrated that implant elements made of organic polymer materials coated with hydroxyapatite having sufficient bonding strength for practical use and excellent performance were successfully obtained.

As described above, the present invention creates bioimplant elements with bone-like hydroxyapatite coating on the surface of organic polymer base materials containing sulfonic group or/and carboxyl group using practically saturated or supersaturated water solution of hydroxyapatite. The bioimplant elements thus obtained have excellent biological compatibility, sufficient strength and design flexibility, and its significant contributions to medical field are expected.

Claims

Claims.

1. Bioimplant elements characterized in that said elements include a base material having a coating of hydroxyapatite formed on the surface thereof.

2. The bioimplant elements of claim 1 further characterized in that said base material is made of an organic polymer containing at least one of a sulfonic group or a carboxyl group contained in at least the surface of said base material.

3. The bioimplant elements described in Claim 2 further characterized in that said organic polymer includes a sulfonic group chosen from a group consisting of polyethersulfon, polysulfon or polyallylsulfon.

A . The bioimplant elements described in Claim 2 further characterized in that said polymer is a compound containing a combination of organic polymers selected from a group consisting of polyethersulfon, polysulfon or polyallylsulfon.

5. The bioimplant elements described in Claim 2 characterized in that said organic polymer containing a carboxyl group is a polymer obtained through copolymerization of olefin and carboxyl acid containing vinyl group and is then bridged with metallic ions.

6. The bioimplant elements described in Claim 2 characterized in that said organic polymer containing a carboxyl group is a compound including a polymer obtained through copolymerization of olefin and carboxyl acid containing vinyl group and is then bridged with metallic ions.

7. The bioimplant elements described in Claims 5 or 6 characterized in that the olefin is thylene.

8. The bioimplant elements described in Claims 5 or 6 characterized in that the carboxylic acid containing vinyl group is methacrylic acid.

9. The bioimplant elements described in Claim 2 further characterized in that the thickness of said hydroxyapatite coating is in the range of about 3-100 μm.

10. The bioimplant elements of claim 1 further characterized in that said coating of hydroxyapatite is formed on the surface of the said base material through contact between said base material and CaO/Si0₂ base glass powder in a practically saturated or supersaturated water solution of hydroxyapatite.

11. The bioimplant elements described in Claim 10 further characterized in that the thickness of said hydroxyapatite coating is in the range of about 3-100 μm.

12. The bioimplant elements described in Claim 10 characterized in that more than 80% of said CaO/Si0₂ base glass powder has grain diameters in the range of about 100- 600 μm.

13. The bioimplant elements of claim 1 further characterized in that said coating of hydroxyapatite is a bone-like coating.

14. The bioimplant elements described in Claim 1 further characterized in that the thickness of said hydroxyapatite coating is in the range of about 3-100 μ .

15. The bioimplant elements described in claim 1 characterized in that the surface of said base material is nonspecular.

16. The bioimplant elements described in Claim 1 characterized in that a part of a phosphate group or hydroxyl group of hydroxyapatite is replaced by a carbonic group.

17. The bioimplant elements described in Claim 1 further characterized in that the thickness of said hydroxyapatite coating is in the range of about 10-60 μm.

18. A method for coating a surface of a bioimplant element with hydroxyapatite characterized by forming the bioimplant element of a base material having at least a surface thereof that includes an organic polymer containing at least one of a sulfonic group or a carboxyl group, and immersing at least a portion of the bioimplant element in a practically saturated or supersaturated water solution of hydroxyapatite.

19. The method for coating of claim 18 further characterized by placing glass powder in the practically saturated or supersaturated water solution of hydroxyapatite so that the glass powder will be in contact with the surface of the bioimplant element to be coated with hydroxyapatite.

20. The method for coating of claim 18 further characterized in that the glass powder includes at least one of CaO or Si0₂.

21. The method for coating of claim 18 further characterized in that more than about 80% of the grains forming the glass powder have grain diameters within a range of about 100 - 600 μm.

22. The method for coating of claim 18 further characterized in that after the bioimplant element is immersed for a desired time in a first practically saturated or supersaturated water solution of hydroxyapatite having the glass powder therein, the bioimplant element is thereafter immersed for a desired time in a second practically saturated or supersaturated water solution of hydroxyapatite having at most substantially less glass powder therein.

23. The method for coating of claim 22 further characterized in that more than about 80% of the grains forming the glass powder in the first solution have grain diameters within a range of about 100 - 600 μ .

24. A method for coating a surface of a bioimplant element with hydroxyapatite characterized by contacting a surface of the bioimplant element with CaO/Si0₂ base glass powder in a practically saturated or supersaturated water solution of hydroxyapatite.

25. The method for coating of claim 24 further characterized in that more than about 80% of the grains forming said glass powder have grain diameters within a range of about 100 - 600 μm.

26. The method for coating of claim 24 further characterized in that the bioimplant element includes a base material having at least a surface thereof that includes an organic polymer containing at least one of a sulfonic group or a carboxyl group.

27. The method for coating of claim 24 further characterized in that after the bioimplant element is immersed for a desired time in a first practically saturated or supersaturated water solution of hydroxyapatite having the glass powder therein, the bioimplant element is thereafter immersed for a desired time in a second practically saturated or supersaturated water solution of hydroxyapatite having at most substantially less glass powder therein.