Title of Invention

A METHOD AND APPARATUS FOR PREPARING A BONE REPLACEMENT MATERIAL

Abstract

1. A method for preparing a bone replacement material, that comprises osteoinductive and/or osteogenic substances with the aid of a syringe wherein A) a biocompatible body (3) with fully interconnecting pores is exposed to a vacuum; and B) that by means of the vacuum created in the pores of the body (3) the osteoinductive and/or osteogenic substances present in a free-flowing form are sucked into these pores. C) the method is carried out with the aid of a syringe including a hollow cylinder (1) and a piston (2), whereby the osteoinductive and/or osteogenic substances present in free-flowing form being absorbed by the syringe and being sucked through the pores of the body (3) accommodated within the hollow cylinder (1) of the syringe.

Full Text

FORM 2 THE PATENTS ACT 1970 [39 OF 1970] & The Patents Rule, 2003 COMPLETE SPECIFICATION [See Section 10 and Rule 13] "A METHOD AND APPARATUS FOR PREPARING A BONE REPLACEMENT MATERIAL" SYNTHES GMBH, of Eimattstrasse 3, CH-4436 Oberdorf, Switzerland, The following specification particularly describes the nature of the invention and the manner in which it is to be performed:- GRANTED 13-10-2006 ORIGINAL 197/MUMNP/2003 FORM 2 THE PATENTS ACT 1970 [39 OF 1970] 8B The Patents Rule, 2003 COMPLETE SPECIFICATION [See Section 10 and Rule 13] "A METHOD AND APPARATUS FOR PREPARING A BONE REPLACEMENT MATERIAL" The following specification particularly describes the nature of the invention and the manner in which it is to be performed:- 1 4 FEB 2006 The invention relates to a method for preparing a bone replacement material, an apparatus for carrying out the method, and to a bone replacement material. A porous hydroxyapatite body which may contain water, aqueous sodium chloride solution, blood, and synthetic blood plasma is known from the Japanese Patent Application No 60 142857 by SUMITOMO CEMENT CO. It is not specified in this document whether the body described is a body with fully interconnecting pores. EP-AO 361 896 shows a prosthesis which functionally replaces the bone. The prosthesis is posed on a frit in an open atmosphere in order to suck a suspension through the pores of the prosthesis by means of its evacuation. This open process is naturally not very efficient. From US 5,876,452 it is known to homogeneously distribute a bioactive agent e.g. cells in the polymer by means of adding them to a polymer solution and subsequent stripping of the polymer-solvent without the formation of pores. From EP-A 0470 303 a granulated material is known which consist of a plurality of individual grains that themselves are not porous. Through application of a vacuum the clearance between the individual grains of granulated material may be filled with blood, but without having coincidentally present pores in the grains of the granulated material are filled with blood due to the lack of vacuum there. Bone replacement materials which are biocompatible and have osteoinductive properties are known from PCT/EP99/00684. The term 'osteoconduction' refers to the growth of osteblasts and to bone regeneration without formation of an intermediate layer taking place on the surface of endogenous material or of implanted exogenous materials, which are not subject to alteration as a consequence of the bone growth. A disadvantage of these known materials consists in their lacking osteoinductive properties. The term 'osteoinductive refers to a basically unphysiological intervention in the tissue distribution of the body. Osteoinduction is to be understood as the process of introducing and stimulating bone formation in a tissue area which does not contain any osseous tissue, i.e. in the present case the interconnecting pore structure of a -biomaterial. The invention is intended to provide a remedy for this. It is accordingly an object of the invention to create a simple and reliable method for preparing a bone replacement material, in particular a material with improved osteoinductive properties. A further object is the creation of an improved bone replacement material. The advantage thus achieved resides in the fact that the somatic cells present in the pores of the biocompatible body (e.g. blood or rather the fibrin' contained therein) form a reticulated structure inducing the ingrowth of new somatic cells into the porous body. The use of blood has the additional advantage that the ingrowth of bone cells into the porous body is encouraged by the growth factors contained in the blood platelets. The method according to the- invention has the advantage that the porous body is not simply immersed in a suspension of somatic cells (e.g. blood) for the pore system to be impregnated therewith as a result of the capillary action but that the interconnecting pores are exposed to a vacuum by which the somatic cells present in a free-flowing form (e.g. in the form of blood or in the form of an. aqueous suspension) are actively sucked into the porous body where they can spread homogeneously, reaching even the innermost portions thereof. The advantages achieved by the present invention consist basically in the fact that the bone replacement material prepared according to the invention has an interconnecting pore structure which when implanted in a defect site is already filled with appropriate somatic cells such as blood, blood constituents, bone marrow, or bone cells (all of which in a fluid form, as appropriate for this purpose) and possesses osteoinductive properties. Similar to the process observed in fracture healing, the blood clot inside the structure will better organise in a granular connective tissue rich in cells and vessels and having a low fibre content, generally referred to as granulation tissue. Various cells enter this tissue and start creating a cartilaginous matrix. This process continues until the totality of the granulation tissue is replaced by cartilage, which will later on calcify. Without the advantages achieved by the invention, the pores would partly be filled only with air, so that the biological process described would be generally slowed down or even made impossible. Instead of using blood or blood composites, which are by definition free-flowing, somatic cells may also be suspended in a biocompatible fluid, preferably an aqueous solution, in order to be apt to be absorbed by the interconnecting pores of the body. According to a preferred method, the somatic cells are selected from the following groups: autologous bone marrow, separated concentrated cells taken from autologous bone marrow, cultured autologous stem cells, differentiated autologous stem cells, or mesenchymal cells. The precursor cells of the peripheral blood cells are continuously formed by immature haematopoietic cells generally referred to as stem cells. Preferably, the somatic cells are of autologous nature, i.e. the donor and the recipient of the somatic cells are identical. In a preferred embodiment of the invention, the somatic cells present in a free-flowing form are mixed with a number of agents inducing bone formation, such as: a) synthetic growth factors; b) recombinant growth factors, preferably growth factor p (TGF-P) or FGF-2 (fibroblast growth factor); c) natural or synthetic peptides; d) platelet derived growth factor (PDGF); e) insulin-like growth factor (IGF) ; f) fibrin as the end product of blood coagulation; or g) synthetic fibrin. Preferably, the body with interconnecting pores used for the method according to the invention consists of a bioresorbable material, preferably hydroxyapatite, tribasic calcium phosphate, or polylactid, or any other bioresorbable polymer or copolymer. The porosity of this body is suitably at least 25 %, preferably at least 35 %. More than 50 % of the pores should suitably have a diameter of between 200 and 500 microns. The connections between the individual pores should suitably have a diameter ranging between 10 and 300 microns, preferably between 200 and 400 microns. In the following, the invention and further developments of the invention will be illustrated in greater detail with reference to one embodiment. In the drawing: Fig. 1 shows a sectional view of a syringe suitable for preparing the bone replacement material according to the invention. The syringe shown in Fig. 1 serves for preparing the bone replacement material according to the invention. It consist of a hollow cylinder 1, a piston 2 movably arranged within the hollow cylinder, and a head portion 4 provided with a screw thread so as to be removable from the front end portion of the hollow cylinder 1. This head portion 4 is equipped with a membrane 5 which, for the purpose of taking the donor's blood, is pierced by an adaptor 6 equipped with a needle 7 passing through said membrane. The use of the adaptor 6 on the head portion 4 permits the adaptation of any standard cannula system (e.g. Luer-system hypodermic needle, catheter, butterfly, etc.) on the syringe. In the hollow cylinder 1, a biocompatible body 3 with interconnecting pores is accommodated which sealingly fits into the front part of the syringe, so that the patient's blood or blood constituents are forced to flow through the body 3. The body 3 consists of a bioresorbable material, preferably of hydroxyapatite, tribasic calcium phosphate, or polylactid. After the blood has been taken from the donor, the adaptor 6 is removed so that the membrane 5 of the head portion 4 will recover its impermeability and the contents of the hollow cylinder 1 of the syringe is again sealed airtight. As the piston 2 is further pulled back within the hollow cylinder 1 of the syringe, a vacuum is created which causes the blood to totally permeate the body 3, penetrating even its innermost portions and displacing the air contained therein. After the body 3 has been impregnated with blood or blood constituents (or with other somatic cells present in a free-flowing form), the head portion 4 is screwed off from the syringe so that the impregnated body 3 may be pushed out of the hollow cylinder 1 by means of the piston 2. The body 3 - after having been shaped, if necessary, into a specific form - may then be inserted into a bore prepared in, or a defect site of, a bone of the patient from whom the blood or other somatic cells required for impregnation have been taken. Due to the interconnecting pore structure of the body 3 and the autologous blood (or blood constituents or other somatic cells) contained in the pore system, the ingrowth of somatic cells into the body 3 is substantially facilitated. WE CLAIM: 1. A method for preparing a bone replacement material, that comprises osteoinductive and/or osteogenic substances with the aid of a syringe wherein A) a biocompatible body (3) with fully interconnecting pores is exposed to a vacuum; and B) that by means of the vacuum created in the pores of the body (3) the osteoinductive and/or osteogenic substances present in a free-flowing form are sucked into these pores. C) the method is carried out with the aid of a syringe including a hollow cylinder (1) and a piston (2), whereby the osteoinductive and/or osteogenic substances present in free-flowing form being absorbed by the syringe and being sucked through the pores of the body (3) accommodated within the hollow cylinder (1) of the syringe. 2. A method as claimed in claim 1, wherein the osteogenic substances are present in form of somatic cells in free-flowing form, whereby the somatic cells are selected from the following groups: a) autologous bone marrow, b) separated concentrated cells taken from autologous bone marrow, c) cultured autologous stem cells, d) differentiated autologous stem cells, or e) mesenchymal cells. 3. A method as claimed in claim 1, wherein the osteoinductive substances are contained in a biocompatible fluid, preferably in an aqueous solution. 4. A method as claimed in claim 1, wherein the osteoinductive substances are suspended in a biocompatible fluid, preferably in an aqueous solution. 5. A method as claimed in claim 4, wherein the somatic cells in free-flowing form are selected from the following groups: A) blood, B) blood constituents, C) bone marrow or D) bone cells in free-flowing form. 6. A method as claimed in any of the claims 1 to 5, wherein the somatic cells are of autologous nature. 7. A method as claimed in any of the claims 1 to 6, wherein the osteoinductive substances are selected from the following groups: a) synthetic growth factors; b) recombinant growth factors, preferably growth factor p (TGF-J3) or FGF-2 (fibroblast growth factor); c) natural or synthetic peptides; d) platelet derived growth factor (PDGF); e) insulin-like growth factor (IGF); f) fibrin as the end product of blood coagulation; or g) synthetic fibrin. 8. A method as claimed in claim 1, that comprises osteoinductive and/or osteogenic substances wherein A) a biocompatible body (3) with fully interconnecting pores is exposed to a vacuum; and B) that by means of the vacuum created in the pores of the body (3) the osteoinductive and/or osteogenic substances present in a free-flowing form are sucked into these pores; whereby C) the method is carried out with the aid of a syringe including a hollow cylinder (1) and a piston (2), whereby the osteoinductive and/or osteogenic substances present in free-flowing form being absorbed by the syringe and being sucked through the pores of the body (3) accommodated within the hollow cylinder (1) of the syringe. 9 A method as claimed in claim 1, wherein the body (3) consists at least in part of a bioresorbable material, preferably of hydroxyapatite or tribasic calcium phosphate. 10. A method as claimed in claim 1, wherein the porosity of the body (3) is at least 25%, preferably at least 35%. 11. A method as claimed in any of the claims 9 and 10, wherein more that 50% of the pores have a diameter ranging between 200 and 500 microns. 12. A method as claimed in any of the claims 9 to 11, wherein the connections between the individual pores have a diameter ranging between 10 and 300 microns, preferably between 200 and 400 microns. 13. An apparatus for carrying out the method as claimed in any of the preceding claims, wherein it consists of a syringe including a hollow cylinder (1) and a piston (2), a biocompatible body (3) with fully interconnecting pores being placed in such a way within the hollow cylinder (1) that it seals the hollow cylinder (1) at least over part of its length, so that the osteoinductive and/or osteogenic substances present in free-flowing form which are absorbed by the syringe are forced to flow through the pores of the body (3). 14. An apparatus as claimed in claim 13, wherein the syringe comprises a head portion (4) equipped with a membrane (5) at the front end of the hollow cylinder (1), such that osteoinductive and/or osteogenic substances present in free-flowing form are forced by means of vacuum to flow through the pores of the body (3) after sealing the membrane (5) and pulling back the piston (2). Dated this 7th day of February, 2003. [DIPAK MUNDRA] OF REMFRY & SAGAR ATTORNEY FOR THE APPICANTS

Documents:

197-mumnp-2003-cancelled pages(13-10-2006).pdf

197-mumnp-2003-claims(granted)-(13-10-2006).doc

197-mumnp-2003-claims(granted)-(13-10-2006).pdf

197-mumnp-2003-correspondence(14-11-2006).pdf

197-mumnp-2003-correspondence-(ipo)-(06-10-2006).pdf

197-mumnp-2003-drawing(14-02-2006).pdf

197-mumnp-2003-form 18(04-08-2005).pdf

197-mumnp-2003-form 1a(06-02-2003).pdf

197-mumnp-2003-form 1a(14-02-2006).pdf

197-mumnp-2003-form 2(granted)-(13-10-2006).doc

197-mumnp-2003-form 2(granted)-(13-10-2006).pdf

197-mumnp-2003-form 3(06-02-2003).pdf

197-mumnp-2003-form 3(14-02-2006).pdf

197-mumnp-2003-form 4(07-02-2006).pdf

197-mumnp-2003-form 5(06-02-2003).pdf

197-mumnp-2003-form 6(14-11-2006).pdf

197-mumnp-2003-form-pct-ipea-409(07-02-2003).pdf

197-mumnp-2003-form-pct-isa-210(07-02-2003).pdf

197-mumnp-2003-petition under rule 137(14-02-2006).pdf

197-mumnp-2003-petition under rule 138(14-02-2006).pdf

197-mumnp-2003-power of authority(14-02-2006).pdf

197-mumnp-2003-power of authority(14-11-2006).pdf

197-mumnp-2003-power of authority(19-12-2002).pdf

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