RU2465017C2 - Method for preparing non-toxic porous implant of polylactic acid for building of long bone defects - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly traumatology and orthopedics, and can find application in treating false joints of long bones. What is described is a method for preparing a non-toxic porous implant of polylactic acid with controlled pore size for building of long bone defects involving melting the polylactic acid granules in a melting pot immersed in thermally stable oil with porogen presented by sodium chloride crystals 100-250 nm to be washed out by aqueous solutions of antiseptics. The implant is prepared with no toxic solvents added and has a pre-set pore diameter.

EFFECT: improved efficiency of the method.

Description

The invention relates to medicine and can be used, in particular, in traumatological and orthopedic practice for the repair of complete defects of the tubular bones with diastasis up to 2-2.5 cm, in particular, with the formation of a defect after resection of the false joint of long tubular bones. In the event of traumatic defects or in other situations related to the planned resection of the pathological site of such a bone, one of the promising methods is to replace the bone defect with a biodegradable implant.

Of the proposed methods, the manufacture of an implant from polylactic acid has recently attracted attention. The advantage of this material is the reactivity of living tissues, hypoallergenicity, sufficiently long degradation, the absence of toxic products during enzymatic depolymerization in tissues (lactic acid enters the Krebs cycle).

Implant Requirements:

It must be porous (Pore diameter 100-200 nm (Cima, LG, Vacanti, JP, Vacanti, C., et al. Tissue engineering by cell transplantation using degradable polymer substrates. J. Biomech. Eng. Pp. 113, 143, 1991), the pores must communicate with each other, which contributes to the germination of granulation tissue, migration of fibroblasts with their transformation into osteoblasts on the pore walls of the matrix with its subsequent biodegradation.

The following methods are known for producing porous material from polylactic acid:

- Leaching particles from an evaporated or lyophilized polymer solution (Mikos AG et al. Preparation and characterization of polylactic acid foams. Polymer, No. 35, p. 1035, 1994), in which the polymer is dissolved in an appropriate organic solvent (xylene, chloroform, methylene chloride), then the corresponding porogen particles insoluble in this solvent (water-soluble salts, etc.) are added to the solution, then the organic solvent is removed and the porogen particles are removed by dissolution in a polar solvent (water, etc.). The advantage of the method is that when using from 70% porogen by weight relative to the weight of the polymer, the resulting pores are highly interconnected. The use of toxic organic solvents with the probability of incomplete removal of them from the porous structure of the material is the disadvantage of this method.

- Foaming gas under high or ultrahigh pressure (Novel approach to fabricate porous sponges of poly (-lactic-co-glycolic acid) without the use of organic solvents. David J. Mooney, Daniel F. Baldwin, Nam P. Suh, Joseph P Vacanti and Robert Langer. Biomaterials Volume 17, Issue 14, July 1996, Pages 1417-1422), requires a long time and / or equipment to create a high pressure of neutral gases.

- Phase separation, spinodal decomposition or emulsification followed by lyophilization, involves toxic high molecular weight organic solvents (naphthalene, phenol, 1,4-dioxane) or, using the emulsification technique followed by cryoliphilization, the resulting pore size usually does not exceed 10-30 nm, which negatively affects the dynamics of biodegradation of the polymer matrix in vivo and does not contribute to cell migration into the pores of the matrix.

- Injection molding after introducing the porogen into the melt, where gelatin is used as the porogen - a biologically inert substance of complex protein structure (Cima, LG, Vacanti, JP, Vacanti, C., et al. Tissue engineering by cell transplantation using degradable polymer substrates. J. Biomech. Eng. Pp. 113, 143, 1991. Thomson, Robert C.1; Yaszemski, Michael J.2; Powers, John M.3; Mikos, Antonios G. Journal of Biomaterials Science, Polymer Edition, Volume 7 , Number 1, 1996, pp. 23-38) having antigenic activity.

The objective of the invention is to develop methods for producing a porous implant from polylactic acid without the use of toxic solvents with a given pore diameter, interconnected.

The problem is solved in that in the method for producing a non-toxic porous implant from polylactic acid to replace defects of long tubular bones, including the melting of granules of polylactic acid in a metal crucible with the addition of porogen, sodium chloride crystals with a size of 100-250 nm are used as a porogen, followed by washing them in distilled water with the addition of antiseptics, while the crucible is immersed in heated heat-resistant mineral oil.

The method is as follows.

Take a sample of polylactic acid granules in an amount of 30 g, salt crystals in an amount of 15 g, crystal size 100-250 nm, placed in a stainless steel crucible. The crucible is heated to a temperature of transition of the polymer into a viscous state (185-190 ° C). The heat transfer to the crucible from the heating element of an electric furnace with a thermostat occurs by immersing the crucible in heat-resistant mineral oil. The temperature is controlled by an electronic thermometer sensor immersed in mineral oil. Upon reaching the desired temperature (~ 190 ° C) and viscosity, the contents of the crucible are mechanically mixed to a homogeneous state. The resulting mass is placed in a cylindrical or other configuration in a metal form and cooled in it. Then, after cooling, the salt is removed from the finished implant by rinsing with aqueous solutions of antiseptics.

The proposed method for producing a highly porous implant from polylactic acid makes it possible to obtain a non-toxic implant that is simple to use and does not require complex hardware design.

The method allows melt the polymer granules evenly without combustion and obtain a porous material with a controlled pore size depending on the size of the porogen particles, with a predictable degree of pore interconnection, not contaminated with organic solvents.

Claims (1)

A method of producing a non-toxic porous implant from polylactic acid to replace bone defects of long tubular bones, which involves the melting of polylactic acid granules in a metal crucible immersed in heat-resistant mineral oil with the addition of porogen, characterized in that sodium chloride crystals of size 100 are used as porogen -250 nm, followed by washing them with aqueous solutions of antiseptics.