JPH0497747A - Artificial bone for transplanting application - Google Patents

Abstract

PURPOSE: To provide an artificial bone implant having a bone growth induction coating or layer by setting a fixing part, of the artificial bone tool to a bone formation composition which is biocompatible and reabsorptive and composed of demineralized bone powder dispersed in a binder. CONSTITUTION: To apply a bone formation coating 30 to a fixing part, of endoprosthesis 10, after binder, for example, is prepared for fine powder having the almost same mean grain size as that of demineralized bone powder and the bone powder is formed into easy-flowable powder mixture by being uniformly mixed with the binder powder and dried, it is put in a space 21 of a mold 20 excessively. Secondly, after the powder mixture is heated, for example, to a temperature sufficient for the binder particles being welded so as to be integrated together, it is cooled to an air temperature so as to provide an artificial organ with coating. At first, after binder solvent solution is applied to a stem part and a part of the solvent is vaporized so that the bone formation coating 30 becomes a sticky membrane, the demineralized bone powder is made to contact with the binder and applied to the surface of the stem part 13 by just coating thereon. Several-time repetition of this method can provide the membrane of a prescribed length. The solvent is completely vaporized so as to complete the bone formation film.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to implantable artificial bone devices, particularly prostheses manufactured as composites containing bone growth-inducing layers or coatings.

[Prior art and issues to be solved]

Many bone prosthetic devices, such as those used in hip joint reconstruction, are mechanically attached to the device by fitting a fixation portion into a medullary tube or into a bone cement such as polymethyl methacrylate. It is joined to the skeleton by fixing it to. However, these methods are not fully satisfactory because the instruments tend to loosen due to impact or as a result of long-term use. In an attempt to secure the prosthetic bone device in place, ingrowth of tissue may occur.
h) is used.

The prosthesis of this method is provided with a porous surface to aid in ingrowth of bone and to serve as an attachment site for new bone tissue. The method of tissue ingrowth to secure a prosthesis has been applied to a variety of endoprostheses.

US Patent No. 3.98 & 212 describes porous polymeric coatings for bone fixation by tissue ingrowth.

Convenient porous polymeric materials are those having interconnected pores of a specified density and a specified average diameter.

Among the polymeric materials that have been published are high density polyethylene and polypropylene or mixtures thereof with certain criticality millimeters. It has also been shown that the coating may be mechanically fixed or chemically bonded to the device.

Similarly, the prosthetic bone device of U.S. Pat.
) is coated with a porous thermoplastic material that has special properties that are said to be inductive.

The fixation part of the endoprosthesis device described in US Pat. No. 4,202,055 has a non-porous polymeric membrane doped with ceramic particles. Resorption of the ceramic particles creates a polymeric structure with continuous pores infiltrated by the newly formed bone.

According to U.S. Pat. No. 4,713.076, the anchoring portion of the prosthetic bone device is coated with a fully resorbable coating that is said to allow rapid and deep ingrowth of new bone tissue and to secure implants within the bone. have. The coating composition is made of calcium compounds, such as tricalcium phosphate or apatite (hydroxylapatite), made into highly porous spherical particles, which include polyamino tufts, polylactates, polyglycolates,
Cocondensates of these materials are embedded in resorbable and biologically compatible binders such as gelatin or collagen.

Other types of coated prosthetic bone devices are disclosed in U.S. Pat.
No. 26, 4 No. 35.069, No. 4365.356, 4
, 491,987, 4652459, 4,702,
No. 930, and No. 4705°694.

The use of comminuted exogenous bone growth material, eg found from demineralized homogeneous or xenogeneic bone, is also known.

No. 4,485,097 and 4,678.
．． 470 and 4743.259; “Use of demineralized bone matrix in the treatment of partial lesions” by Bolander et al. “The Journal of Bon@
and Jolnt Surgery, Volume 68-A, Volume 8.1264-1273: Glowacki et al. 2
33-241 (1985); Gepstein et al. “Bridging large bone defects with powdered demineralized bone matrix” Th@ Jotlrnal of Bone
and Bone Surgery.

Vol. 69-A, B. 7.984-991 (1987); "Demineralized Freeze-dried Bone Allograft as Implant Material for Human Periodontal Ligament Defects" by Melonitz The In
international.

Journal of Psriodonties
and Rs+5tsrativeDenti@
Try, 41-55, "Treatment of Jaw Defects by Demineralized Bone Inclusion I" by George (June 1984) and Kaban et al., Journal of Oral An.
d Maxills Facial Surgery. However, conventional descriptions do not give any suggestions regarding the combination of these artificial bone components and bone growth-inducing components based on powdered bone substances.

[Solving issues]

The object of the present invention is to
The present invention provides an artificial bone implant having a bone growth inducing coating or layer thereon.

The object of the present invention is to provide the fixation part with an osteogenic coating or layer of demineralized bone powder dispersed in a pyococcinoplete and in a resorbable binder. The object of the present invention is to provide a coated endoprosthesis, for example a hip joint replacement.

For these and other purposes of the invention, an artificial bone implant having an anchoring portion in contact with bone tissue is provided with a biocontact tiple applied to the surface of at least a portion of the anchoring portion; A coating or layer that induces bone attachment consisting of demineralized bone powder dispersed in a resorbable binder is provided.

As the binder is gradually resorbed, the void thus created will be occupied by new bone growth, which will connect the prosthesis to the pre-existing bone tissue. To cause a strong bond between the two.

Known prosthetic coatings, such as U.S. Pat.
In contrast to the osteogenic particles contained in those described in US Pat. giving an effect.

The present invention will be further explained based on specific embodiments thereof.

The demineralized powdered or ground bone added to the osteogenic layer or coating is of a known type and produced by known methods.

In a preferred method for demineralizing bone, the bone is first ground to the desired average particle size, then degreased/disinfected and demineralized with acid. Preferred degreasing and disinfecting solutions are ethanol and aqueous solutions. Ethanol is a good solvent for lipids and water is a good hydrophilic carrier that allows solutions to penetrate deeper into bone. Aqueous ethanol solutions kill vegetative microorganisms and viruses and also disinfect bones. Approximately 10-40% water (i.e. approximately 60-90% degreasing agent such as alcohol) is present in the degreasing and disinfecting solution for optimal lipid removal and disinfection in the shortest time possible. There is a need to. The preferred concentration of the degreasing solution is approximately 60% alcohol.
854 to 854, preferably 70%. After degreasing, bones are 0
．． 6 Soak in a moromi with a pH level of 4, such as N Danpu, for about 3 hours to demineralize it. Other enzymes that can be used at the same or different concentrations include inorganic acids and synthetic ferments such as peracetic acid. The powder after acid treatment is 0.
The pH is finally adjusted by washing with water for injection buffered with a buffer such as 1M sodium phosphate solution, followed by a final wash with water for injection to remove residual hydrochloric acid and sodium phosphate. This mineralized bone powder can be used immediately to manufacture the coated prosthetic bone devices of the present invention, or it can be stored in aseptic conditions, preferably in frozen conditions, prior to use.

The size of the skeleton particles can vary over a wide range.

The average particle size can vary within a range of about 100 microns to about 20 millimeters, preferably about 200 microns to about 15 millimeters (suitable for boat fishing in most cases). The amount of bone powder that can be added to the binder to provide the osteogenic layer or coating of the invention can also vary within a wide range;
About 5 to about 80% by weight, preferably about 20 to about 60% by weight
The bone powder can be modified in one or more ways if necessary, in varying amounts (suitable in most cases).

For example, the porosity of bone powder can increase it. In addition, bone powder may be added with a denaturing agent having a Vi2 or more, such as US Pat. No. 46'
It can be treated with glutaraldehyde as described in 1470. #'i US Pat. No. 4,743. among other optional treatments.
There is a method for increasing the protein content of powdered bone using the 259 method. It is also possible to introduce various substances into the bone particles by soaking the bone powder in a solution of the desired substance before adding it to the binder and drying the bone particles. Substances that can be easily added to the bone particles by these methods include antiviral drugs, such as those suitable for preventing acquired immunodeficiency syndrome (AIDS) transmission; erythromycin, pandrazine, neomycin, penicillin, polymyxin B; Antibacterial agents and/or antibiotics such as , tetracyclines, viomycin, chloromycetin, and streftomycin, cefazolin, ampicillin, tobramycin, clindamycin, and gentamicin; amino acids, diptide, vitamins, inorganic elements, NAD and ( or) other nutrients; hormones; endocrine gland tissue or tissues, fragments; synthesizers: enzymes such as collagenases, butidases, oxidermos, etc.; polymeric cell skeletons with dormant cells; angiogenic agents; Polymeric carriers carrying these drugs; collagen lattes; biocompatible surfactants; antigenicity-forming agents; cytoskeletal agents; bone morphogenetic proteins (BM
Pa), transforming growth factor (TCP-β)
, biologically active ingredients such as insulin-like growth factor (IGD-1); mesophyll elements; osteolytic agents; anti-tumor agents; thin-chest attractants and adhesives; immunosuppressive agents; and nucleic acids.

In addition to or as an alternative to adding such materials to the demineralized bone powder, these and other materials may be incorporated into the binder of the osteogenic coating or layer. Can also be added.

The amounts of optionally added substances can vary widely, and optimum amounts can be readily determined for a particular case, usually by experimentation.

In the present invention, as a binder for the osteogenic layer or osteogenic coating, a resorbable and resorbable substance, i.e., bioerodable (biod@gr.
available ) or bioero double (bioe
(rodable) materials are available. Such materials which may be advantageously used include polyglycolic acid, polydemulcent, glycolide-lactide copolymers, such as 1-caprolactone or 1-caprolactone.
Other copolymers of the above may be modified with chamozuma, polyethylene oxide-polyethylene terephthalate copolymers, U.S. Pat. No. 4,826.94.
Polyester-amides disclosed in No. 5, Rosan
et al., Biomaterials, 4,131 (1
983) and Leong et al., J., Biomsd., M.
ater, Res, L 9(8), 941 (1985
), the polybrush anhydride disclosed in U.S. Pat. No. 4,826.
Polyether glycol-based multiblock copolymers disclosed in US Pat. Examples include collagen or cross-linked collagen and chitin.

Reference is made to U.S. Pat. No. 4,485,097, the contents of which are incorporated herein by reference, to describe collagen containing demineralized bone powder that can be applied to implantable bone prostheses in accordance with the present invention. Additions may be added - if desired, the binder can include reinforcing agents, such as fibrous or particulate reinforcing agents, to increase the stiffness of the osteogenic coating.

Although the invention will now be specifically described with respect to a hip endoprosthesis, it can be implemented in any type of bone implant or substitute, such as those used in dental or maxillofacial reconstruction.

As shown in Figures 1 to 5, components 1 of the femoral bone of the known type of hip prosthesis are made of various materials such as metals, ceramics, polymers and composites thereof. Manufactured from bioengineered materials.The prosthesis includes a headpiece 11 and a neck part 1.
2 and a stem portion 13 which serves to secure the implant within the medullary tube of the femur 50.

When applying the osteogenic layer 30 described in FIGS. 1 to 3,
The femoral frame member 10 is placed within the hole portion of the mold 20 (as shown in other mating molds).
, and there is a space or gap 21 defined by the surface of the stem 13 and the wall of the mold hole, which corresponds to the shape and thickness of the osteogenic layer applied to the stem.

In one convenient method of applying an osteogenic coating, a plasticized body of binder is first combined with a demineralized mass that is substantially uniformly incorporated therein. Manufactured by Thus, for example, if the binder is a glycolide-lactide copolymer, a resin may be plasticized in one stroke using a suitable solvent such as benzene, toluene, xylene, etc., and then bone powder may be uniformly added thereto. be done. The flowable material is applied in excess to the surface of the stem portion 13, and when the prosthesis is placed in the mold and the mold is closed, the excess material is forced out of the mold. Alternatively, the uncovered prosthesis is placed in the mold piece 20, the rest of the mold is tamed and secured, and the plastic osteogenic invasive material is injected into the space 21 until there is an excess. After the formation of the osteogenic layer 30 around the system part 13 as shown in FIG. 2, the prosthesis is removed from the mold and the plasticizing solvent is evaporated, resulting in a coated prosthesis as shown in FIG. 3, which is disinfected. and stored aseptically.

In another method of applying the osteogenic coating 30 to the fixation portion of the endoprosthesis 10, the bonding agent is one, e.g.
Prepared as a fine powder with an average particle size approximately the same as the demineralized powder particle size, the bone powder is uniformly mixed with the binder powder to form a dry, free-flowing powder mixture, and then molded into the mold 20.
is placed in excess in the space 21 of. The powder mixture is then heated to a temperature that will form a self-supporting adhesive coating, such as sufficiently warm to cause the binder particles to weld together, and cooled to ambient temperature to form a coated artificial coating of the present invention. Organs can be changed.

The osteogenic coating 30 is prepared by first applying a solvent solution of a binder to the stem portion, evaporating a portion of the solvent to form a sticky film, and then contacting demineralized bone powder with the binder. By attaching it thereto, it can be applied to the surface of the stem portion 13.

By repeating this method several times, a film of desired thickness can be produced. The osteogenic membrane is completed by complete evaporation of the solvent.

Another method, particularly suitable for imparting an osteogenic layer on its base using soluble collagen as a binder, is to place the prosthesis in an aqueous gel of collagen in which demineralized bone powder is suspended. After soaking, the gel is then dried and the collagen binder is cross-linked to the desired degree, if necessary, using a cross-linking agent such as formaldehyde according to known methods.

The thickness of the osteogenic membrane or layer is not particularly critical. An average thickness of about 1 to about 50 mils, preferably about 10 to about 40 mils, will generally result in the collapse of the surface of the stem portion 13 to which a prosthesis, such as an osteogenic coating or layer, is to be applied if necessary. may be pretreated one or more times to ensure good adhesion of the coating or layer thereto. For example, the prosthesis surface can be provided with an adhesion-promoting pattern as described in US Pat. No. 4,778,469 or a rough surface morphology to promote adhesion as described in US Pat.

The following examples are intended to specifically illustrate the implantable artificial bone and osteogenic coating compositions of the present invention.

EXAMPLE Preparation of Demineralized Cortical Bone Powder A fixed amount of ground and sieved cortical bone having an average diameter of about 100 to about 300 microns was placed in a reactor and capped. 30 per gram of bone
-, then stirred for 1 hour (Bolander et al., Journal of B
one and joint surgery, 68-
Volume A, A8 (October 1986)), the bone powder was degreased and sterilized. 50 per gram of post-exhaust ethanol
- into the reactor (Bolander et al.,
above), the reaction was carried out for 3 hours. (Browacki, AATB
Work II hop, 11th annual meeting (1987)),
Drain the salt brew and add water for injection (WFI) to 5 WFI.
Drain the WFI and immerse the bone in a 1M sodium phosphate solution until the pH of the solution is a.
It was repeated until the value was 8 to 7.4. The WFI washing procedure was repeated to obtain a demineralized pre-cortical powder that could be used in subsequent applications.

B. Applying a binder solution, which is a xylene solution of demineralized glycolide-lactide copolymer to the stem of a hip endoprosthesis, and adding 20% by weight of a powder of glycolide-lactide copolymer (approximately 20 moles of glycolide) to 80% by weight.
was prepared by dissolving it in xylene. The stem of the hip prosthesis was immersed in a binder solution, the solution was allowed to dry to a sticky consistency, and a bed of bone powder was sprinkled onto the binder surface to adhere.

This process was repeated several times to form an osteogenic layer with an average thickness of about 2-3 inches containing about 40 to about 50% by weight of demineralized cortical bone powder on the surface of the artificial bone stem. After complete evaporation of the solvent in a drying chamber, the coated prosthesis was sterilized and packaged in a known and conventional manner.

[Brief explanation of the drawing]

In the accompanying drawings, each number indicates the same part. 1 to 3 sequentially show side views at various stages of an example in which a coating that induces bone growth is applied to a fixing member on the femoral side of a hip joint endoprosthesis. Figure 4Fi shows an enlarged cross-section of a bone growth-inducing coating as applied to the hip endoprosthesis of Figure 3; FIG. 5 shows the insertion of a covered hip endoprosthesis viewed within the medullary canal of a femur.

Claims (13)

[Claims] 1. that the fixation portion of the prosthetic bone device has an adhesive coating of an osteogenic composition consisting of demineralized bone powder dispersed in a biocompatible and resorbable binder; Characteristic artificial bone devices. 2. The average particle size of demineralized bone powder is approximately 100
The prosthetic bone device of claim 1, which is between microns and about 200 millimeters. 3. The average particle size of demineralized bone powder is approximately 200
The prosthetic bone device of claim 1, which is between microns and about 15 millimeters. 4. The prosthetic bone device of claim 1, wherein the osteogenic coating comprises from about 5 to about 80% by weight demineralized bone powder. 5. The osteogenic coating is about 20 to about 60% by weight.
2. The prosthetic bone device of claim 1, comprising demineralized bone powder. 6. The artificial bone device according to claim 1, wherein the demineralized bone powder is derived from cortical bone (bone cortex). 7. The binder is polygolic acid, polylactic acid, glycolide-lactide copolymer, glycolide-lactide copolymer modified with one or more monomers copolymerizable therewith, polyethylene oxide-
Polyethylene terephthalate copolymers, polyesteramides, polyanhydrides, polyether glycol-based multiblock copolymers, bioerodible cyanoacrylates, orthoester polymers, orthocarbonate polymers, crosslinked and non-crosslinked collagen and chitin. The artificial bone device according to claim 1, which is selected from the group consisting of. 8. The prosthetic bone device of claim 1, wherein the osteogenic layer or coating contains at least one additional component selected from the group consisting of reinforcing fibers and reinforcing particles. 9. The osteogenic layer or coating contains polymeric cells with antiviral agents, antibacterial agents, antibiotics, amino acids, peptides, vitamins, inorganic elements, NAD, hormones, endocrine tissue, synthesizers, enzymes, parenchymal cells. Skeleton forming agents, angiogenic agents, polymerizable drug carriers, collagen lattes, antigenicity forming agents, cytoskeleton agents, biologically active ingredients, mesenchymal agents, osteolytic agents, antitumor agents, cell attractants, cell adhesives The artificial bone device of claim 1, further comprising at least one additional component selected from the group consisting of , an immunosuppressant, and a nucleic acid in addition to the bone particles or the binding agent or both. . 10. The prosthetic bone device of claim 1, wherein the osteogenic layer has a thickness of about 1 to about 50 mils. 11. The prosthetic bone device of claim 1, wherein the osteogenic layer has a thickness of about 10 to about 40 mils. 12. The artificial bone device according to claim 1, wherein the fixation portion is provided with an adhesion promoting surface before application of the osteogenic composition. 13. The prosthetic bone device of claim 1, wherein the device is an orthopedic, dental, or maxillofacial prosthesis.