KR20210001474A - Membrane for guided bone regeneration and method of manufacturing thereof - Google Patents

Abstract

An embodiment of the present invention provides a method for preparing a membrane for periodontal regeneration, comprising the steps of: (A) preparing a first polymer film, of which the pore shape is controlled, by processing a synthetic polymer resin; and (B) laminating and adhering one or more of the first polymer film and one or more second polymer films comprising a natural polymer resin.

Description

Membrane for periodontal regeneration and its manufacturing method {MEMBRANE FOR GUIDED BONE REGENERATION AND METHOD OF MANUFACTURING THEREOF}

The present invention relates to a membrane for periodontal regeneration and a method for manufacturing the same, and more particularly, periodontal used in bone-guided regeneration to provide a bone formation space by preventing the penetration of soft tissue cells into the bone graft material while the lost alveolar bone is restored. It relates to a membrane for regeneration.

There are increasing cases in which the function of teeth is lost due to the aging of the population, or periodontals are lost due to long-term neglect of tooth defects or fail to function properly. If only the tooth function is lost, the function can be restored by placing an artificial tooth through an implant procedure, but if the periodontal is lost, a guided bone regeneration (GBR) procedure that forms a new periodontal through bone graft is performed. After that, artificial teeth should be placed.

In general, bone-guided regeneration is performed using absorbable periodontal regeneration membranes and various bone materials. Among them, the periodontal regeneration membrane is also called a shielding membrane. It prevents the rapid regeneration of the gingival epithelium from penetrating into the damaged area first, and provides adequate space maintenance. It has a role to help in the differentiation of connective tissue and bone regeneration.

Collagen membranes used in many conventional techniques generally use animal-derived collagen as an absorbent membrane, so the success rate of bone regeneration is high, and removal surgery is unnecessary, but the rigidity of the membrane itself is low, so that the bone graft material is applied to the graft section. It is not easy to fix, and the retention after molding may be poor due to elasticity, and it is difficult to fix it in an accurate position due to being torn or pushed, so that the bone graft material may fall out or move through these gaps. In addition, the absorbent membrane may be absorbed at an early stage, so that the bone tissue regeneration effect may be lowered.

In the case of an absorbent membrane made of a synthetic polymer, the space retention function can be adjusted according to the material or ratio of the polymer, but there is a problem in that it is difficult to mold or cut to apply the membrane to the affected area. In addition, polyester-based synthetic polymers have a disadvantage in that biocompatibility is lower than that of collagen materials because they lower the acidity of surrounding tissues when decomposed due to the nature of the material.

It is known that the non-absorbent shielding film composed of titanium has excellent space retention power by retaining the inherent rigidity of the metal, and as a result, a large amount of bone grafting is possible. However, the titanium shielding film requires additional shaping according to the individual periodontal shape of the patient, and it is inconvenient to be removed through a separate secondary surgery after alveolar bone regeneration. In particular, due to the phenomenon that the bent portion locally protrudes excessively during the molding process, the protrusion may penetrate the gingiva during the bone regeneration induction period and cause infection from the outside.

For this reason, it is necessary to develop a product that solves the disadvantages of the conventional shielding film.

On the other hand, Korean Patent Registration No. 10-1649125 provides a method of manufacturing a membrane for periodontal regeneration in which a biomaterial is laminated on a biodegradable polymer, and through this, a high spatial maintenance capability has been implemented. However, since the membrane for periodontal regeneration is provided in a thermoformed state in a bending structure, it is difficult for the operator to form the shielding film according to the oral structure and shape of the patient, so there is a limitation in terms of convenience of the procedure. In addition, since the biodegradable polymer also releases acid upon decomposition, it is necessary to minimize the use of these polymers.

Korean Patent Registration No. 10-1649125 (2016.08.11.)

The present invention is to solve the problems of the prior art, and an object of the present invention is to provide a membrane for periodontal regeneration and a method of manufacturing the same, which has excellent space retention and moldability while using a minimum of synthetic polymer resin.

One aspect of the present invention, (A) processing a synthetic polymer resin to prepare a first polymer film whose pore shape is controlled; And (B) laminating and bonding at least one of the first polymer film and the second polymer film including a natural polymer resin, respectively; comprising, a method for producing a membrane for periodontal regeneration.

In one embodiment, in step (A), the processing may be performed by additive manufacturing.

In one embodiment, the synthetic polymer resin is PLA (polylactic acid), PGA (polyglycolic acid), PLGA (poly lactic-co-glycolic acid), PLLA (poly (L-lactic acid)), PCL (polycaprolactone), It may be one selected from the group consisting of poly lactide-co-caprolactone (PLCL), polyhydroxybutyrate (PHB), polyhydroxyvalerate (PHV), polydioxanone (PDO), polytrimethylenecarbonate (PTMC), and combinations of two or more of them.

In one embodiment, the content of the synthetic polymer resin included in the first polymer film may be 150 to 750 mg/cm ³ .

In one embodiment, step (A) may include the following steps. (a1) dissolving the synthetic polymer resin; (a2) outputting the product of step (a1); And (a3) cooling the product of step (a2).

In one embodiment, in the step (a1), the dissolution may be performed at 150 to 250° C. for 0.5 to 4 hours.

In one embodiment, in step (a2), the output may be performed by one method selected from the group consisting of casting, melt compression, injection, 3D printing, and a combination of two or more of them.

In an embodiment, in step (a2), the output may be performed to have one pore shape selected from the group consisting of a square, a hexagon, an octagon, and a combination of two or more of them.

In an embodiment, in step (a2), the output may be performed to satisfy at least one of the following conditions. (i) 0.1 to 1 mm thick; (ii) 0.1~0.5mm of pore wall width; (iii) Average pore size 0.1~5mm.

In an embodiment, in the step (a3), the cooling may be performed for 1 to 30 minutes at a temperature below room temperature (25°C).

In one embodiment, the natural polymer resin may be one selected from the group consisting of collagen, chitosan, hyaluronic acid, carboxymethylcellulose, heparan sulfate, dextran, alginate, and combinations of two or more of them.

In one embodiment, step (B) may include the following steps. (b1) laminating a second polymer film including the first polymer film and a natural polymer resin; (b2) heating the product of step (b1) to 30 to 80°C; (b3) bonding the product of step (b2) at a pressure of 3 to 30 mPa; And (b4) cooling the product of step (b3) for 1 minute to 3 hours.

In an embodiment, in the step (b1), the lamination may be performed by intersecting at least one of the first polymer film and the at least one second polymer film to form two or more layers.

In one embodiment, after the step (b4), (b5) cutting the product of step (b4) into a predetermined shape; And (b6) packaging the product of step (b5) after sterilization.

According to an aspect of the present invention, it is possible to maintain space retention and moldability while minimizing the content of the synthetic polymer resin.

The effects of the present invention are not limited to the above effects, and should be understood to include all effects that can be deduced from the configuration of the invention described in the detailed description or claims of the present invention.

1 is a schematic diagram of a method of manufacturing a first polymer film according to an embodiment of the present invention,
2 is a schematic diagram of a method of manufacturing a membrane for periodontal regeneration according to an embodiment of the present invention,
3 shows the shape of the synthetic polymer film according to an embodiment of the present invention,
4 is a photograph of an apparatus for measuring space maintenance (bending strength) of a membrane for periodontal regeneration according to an embodiment of the present invention,
5 is a measurement result of spatial maintenance (bending strength) of a membrane for periodontal regeneration according to Examples and Comparative Examples of the present invention.

Hereinafter, the present invention will be described with reference to the accompanying drawings. However, the present invention may be implemented in various different forms, and therefore is not limited to the embodiments described herein. In the drawings, parts irrelevant to the description are omitted in order to clearly describe the present invention, and similar reference numerals are assigned to similar parts throughout the specification.

Throughout the specification, when a part is said to be "connected" to another part, this includes not only "directly connected" but also "indirectly connected" with another member interposed therebetween. . In addition, when a part "includes" a certain component, it means that other components may be further provided, rather than excluding other components unless specifically stated to the contrary.

When a range of numerical values is described herein, the value has the precision of significant figures provided according to the standard rules in chemistry for significant figures, unless a specific range thereof is stated otherwise. For example, 10 includes a range of 5.0 to 14.9, and the number 10.0 includes a range of 9.50 to 10.49.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

A method of manufacturing a membrane for periodontal regeneration according to an aspect of the present invention includes the steps of: (A) manufacturing a first polymer film having a controlled pore shape by processing a synthetic polymer resin; And (B) laminating and bonding at least one of the first polymer film and the second polymer film including a natural polymer resin, respectively.

In the step (A), the processing is one selected from the group consisting of casting, melt compression, extrusion, injection, additive manufacturing, and a combination of two or more of them, preferably additive manufacturing, that is, 3D printing method. Can be done with For example, the 3D printing is a FDM (Fused Deposition Modeling) method, SLA (Stereo Lithography Appratus) method, DLP (Digital Light Processing) method, SLS (Selective Laser Sintering) method, CJP (Color Jetting Printing) method according to the type of material. ) Method, MJP (Multi Jet Printing) method, LOM (Laminated Object Manufacturing) method, PLT (Paper Lamination Technology) method, or a polyjet method 3D printer, but is not limited thereto. The processing may be performed by freely employing the first polymer film according to the material and use as long as it can be controlled to have a predetermined pore shape.

The first and the number of the synthetic polymer resin content is 150mg / cm ³ or higher, 200mg / cm ³ or higher, 250mg / cm ³ or more, ³ or more or 350mg / cm ³ 300mg / cm of more than included in the first polymer film, 750mg / cm ³ Or less, 700mg/cm ³ Or less, 650mg/cm ³ Or less, 600mg/cm ³ Less than 550mg/cm ³ Or less, 500mg/cm ³ Or less, 450mg/cm ³ Or less or 400mg/cm ³ It can be below.

The synthetic polymer resin is PLA (polylactic acid), PGA (polyglycolic acid), PLGA (poly lactic-co-glycolic acid), PLLA (poly (L-lactic acid)), PCL (polycaprolactone), PLCL (poly lactide-co). -caprolactone), PHB (polyhydroxybutyrate), PHV (polyhydroxyvalerate), PDO (polydioxanone), PTMC (Polytrimethylenecarbonate), and may be one selected from the group consisting of two or more combinations thereof.

The synthetic polymer resin can improve the physical properties required for the periodontal regeneration membrane, such as space maintenance/formability, but has a disadvantage of lack of biocompatibility due to the problem of releasing acid upon decomposition. The present invention can minimize the content of synthetic polymer resin per unit volume by introducing a polymer film of a specific shape, and at the same time realize the performance required for a membrane for periodontal regeneration.

1 is a schematic diagram of a method of manufacturing a first polymer film, that is, a film including a synthetic polymer resin according to an embodiment of the present invention. Referring to FIG. 1, step (A) may include the following steps. (a1) dissolving the synthetic polymer resin; (a2) outputting the product of step (a1); And (a3) cooling the product of step (a2).

In the step (a1), the dissolution is 50°C or more, 75°C or more, 100°C or more, 125°C or more, 150°C or more, or 175°C or more, 300°C or less, 275°C or less, 250°C or less, 225°C or less, or It may be performed at 200° C. for 0.5 hours or more, 1 hour or more, 1.5 hours or more or 2 hours or more, 4 hours or less, 3.5 hours or less, 3 hours or less, or 2.5 hours or less. The melting temperature and time may be selected within a range suitable for output according to the type of the synthetic polymer resin, but is not limited thereto.

In the step (a2), the output may be performed by one method selected from the group consisting of casting, melt compression, injection, 3D printing, and a combination of two or more of them. That is, the output is to inject the product of step (a1) into a mold or mold, and then cool and/or dry it to produce a film whose pore shape is controlled, or to output a film having a specific pore shape using a 3D printer. It can be performed without being bound by a method such as

In the step (a2), the output may be performed to have one pore shape selected from the group consisting of a square, a hexagon, an octagon, and a combination of two or more of them.

3 shows the shape of the polymer film in which the pore shape is controlled. Referring to FIG. 3, a polymer film in which the pore shape is controlled to be a square, a hexagon, or to include an octagon and a square at the same time can be confirmed.

In step (a2), the output may be performed to satisfy at least one of the following conditions. (i) 0.1 to 1 mm thick; (ii) 0.1~0.5mm of pore wall width; (iii) Average pore size 0.1~5mm. The thickness refers to the thickness in the direction in which the first polymer film is stacked, the pore wall width refers to the wall surface width of the pores formed in the first polymer film, and the average pore size is, for example, each pore It may be an average of the pore size, which is an average value of the maximum and minimum values of the diameter passing through the midpoint of.

In the step (a3), the cooling may be performed for 1 to 30 minutes at a temperature of room temperature (25° C.) or less.

The first polymer film prepared in step (A) contains a minimum amount of synthetic polymer resin by adjusting the thickness, pore size, pore wall width, and shape as necessary, and at the same time, it is possible to implement the necessary level of physical properties for a membrane for periodontal regeneration. have.

The natural polymer resin may be one selected from the group consisting of collagen, chitosan, hyaluronic acid, carboxymethylcellulose, heparan sulfate, dextran, alginate, and combinations of two or more of them. The collagen may be extracted from, for example, skin, pericardium, and tendon of porcine or bovine.

2 is a schematic diagram of an example of step (B) according to an embodiment of the present invention. Referring to FIG. 2, the step (B) may include the following steps. (b1) laminating a second polymer film including the first polymer film and a natural polymer resin; (b2) heating the product of step (b1) to 30 to 80°C; (b3) bonding the product of step (b2) at a pressure of 3 to 30 mPa; And (b4) cooling the product of step (b3) for 1 minute to 3 hours. Each of these steps may be performed using a thermocompressor or the like.

In the step (b1), the lamination may be performed by intersecting at least one of the first polymer film and the at least one second polymer film to form two or more layers. For example, a first polymer film / two layers of a second polymer film, a first polymer film / a second polymer film / a first polymer film or a second polymer film / a first polymer film / three layers of a second polymer film, etc. It can be laminated in various forms as needed, such as 4 layers, 5 layers, 6 layers, 7 layers, 8 layers, 9 layers, or 10 layers.

In step (b2), the product of step (b1) is heated to a temperature _equal to or higher than the glass transition temperature (T _g ) of the synthetic polymer resin to melt a part of the film, and in step (b3), the heated (b2) After bonding the film of each layer by pressing the product of step), in the step (b4), the product of step (b3) is cooled to form a membrane for periodontal regeneration in which a natural polymer film and a synthetic polymer film are combined. Can be manufactured.

After step (b4), (b5) cutting the product of step (b4) into a predetermined shape; And (b6) packaging the product of step (b5) after sterilization.

Hereinafter, embodiments of the present invention will be described in more detail. However, the following experimental results are only representative of the above examples, and cannot be interpreted as the scope and content of the present invention are reduced or limited by examples. Effects of each of the various embodiments of the present invention not explicitly presented below will be specifically described in the corresponding section.

Example

Preparation of natural polymer layer

20 g of collagen was dissolved in 1 L of phosphoric acid aqueous solution, and treated with PBS (phosphate buffered saline) solution at 25° C. for 20 hours to fiberize the collagen, and then freeze-dried for 40 hours to prepare a sheet, and glutaraldehyde as a crosslinking agent. The sheet was chemically crosslinked using. After crosslinking, the sheet was washed to remove the crosslinking agent remaining on the sheet, and dried with warm air at 25° C. for 12 hours using wind. The dried sheet was pressed at 50° C. for 2 hours to obtain a natural polymer layer having a thickness of 0.2 mm.

Preparation of synthetic polymer layer

Polycaprolactone (PCL) was supplied to a 3D printer nozzle having a diameter of 0.2 mm, the nozzle was heated to 130° C. to melt polycaprolactone, and then injected at a pressure of 300 kPa to prepare a base film. The injected base film was cooled at 25° C. for 5 minutes to obtain a synthetic polymer layer that satisfies the conditions of Table 1 below.

division Pore wall width (mm) Pore shape Average pore size (mm) Synthetic polymer content
(mg/cm ³ ) Example 1 0.2 square 2 410 Example 2 0.2 square 4 310 Example 3 0.4 square 2 630 Example 4 0.4 square 4 390 Example 5 0.2 Hexagon 2 320 Example 6 0.2 Hexagon 4 270 Example 7 0.4 Hexagon 2 500 Example 8 0.4 Hexagon 4 360 Example 9 0.2 Octagonal 2 390 Example 10 0.4 Octagonal 4 380

An example of the synthetic polymer layer having different pore wall widths, pore shapes, and average pore sizes is illustrated in FIG. 3.

Preparation of membrane for periodontal regeneration

After laminating the natural polymer layer on both sides of the synthetic polymer layer, it was thermoformed for 5 minutes under conditions of 80°C and 20 mPa with a plate-shaped thermocompressor (Cumesis, QM900M) to form a membrane for periodontal regeneration with a thickness of 0.4 mm. Was prepared.

After cooling the shielding film, the protruding portion of the natural or synthetic polymer layer was cut. After gamma sterilization by irradiating 25kGy gamma rays onto the shielding film under vacuum, the sealed packaging was performed.

Comparative Example 1

A membrane for periodontal regeneration (Bio-Gide ^TM , Geistlich company, 0.5 mm thickness) of a collagen material that has been commercially available was prepared.

Comparative Example 2

A membrane for periodontal regeneration (OssGuide ^TM , SK Bioland, 0.5 mm thick) of a collagen material that has been commercially available was prepared.

Experimental Example 1: Space maintenance evaluation

The space retention capacity of the membranes for periodontal regeneration according to Examples and Comparative Examples was compared and evaluated. In order to evaluate the space maintenance, the bending strength was measured using the push-pull gauge (HG-500) of FIG. 4, and the results are shown in FIG.

Referring to FIG. 6, Comparative Examples 1 and 2, which are membranes for periodontal regeneration of the existing collagen material, both exhibited a low bending strength of less than 1N, but the bending strength of the shielding film according to Examples 1-10 was 3-12N or more. Compared to Comparative Examples 1 and 2, remarkably excellent fixing power was implemented. In addition, physical properties of the shielding film may be controlled by adjusting the wall width, shape, and size of the pores of the intermediate layer.

The above description of the present invention is for illustrative purposes only, and those of ordinary skill in the art to which the present invention pertains will be able to understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative and non-limiting in all respects. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as being distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the claims to be described later, and all changes or modified forms derived from the meaning and scope of the claims and the concept of equivalents thereof should be construed as being included in the scope of the present invention.

Claims (15)

(A) manufacturing a first polymer film having a controlled pore shape by processing a synthetic polymer resin; And
(B) laminating and bonding at least one of the first polymer film and the second polymer film including a natural polymer resin, respectively; comprising, a method for producing a membrane for periodontal regeneration. The method of claim 1,
In the step (A), the processing is performed by additive manufacturing, a method of manufacturing a membrane for periodontal regeneration. The method of claim 1,
The synthetic polymer resin is PLA (polylactic acid), PGA (polyglycolic acid), PLGA (poly lactic-co-glycolic acid), PLLA (poly (L-lactic acid)), PCL (polycaprolactone), PLCL (poly lactide-co). -caprolactone), PHB (polyhydroxybutyrate), PHV (polyhydroxyvalerate), PDO (polydioxanone), PTMC (Polytrimethylenecarbonate), and one selected from the group consisting of a combination of two or more of them, a method for producing a membrane for periodontal regeneration. The method of claim 1,
The content of the synthetic polymer resin contained in the first polymer film is 150 ~ 750mg / cm ³ , a method of manufacturing a membrane for periodontal regeneration. The method of claim 1,
The step (A) comprises the following steps, a method for producing a membrane for periodontal regeneration:
(a1) dissolving the synthetic polymer resin;
(a2) outputting the product of step (a1); And
(a3) cooling the product of step (a2). The method of claim 5,
In the step (a1), the dissolution is performed at 50 to 300° C. for 0.5 to 4 hours, a method of manufacturing a membrane for periodontal regeneration. The method of claim 5,
In the step (a2), the output is performed by one method selected from the group consisting of casting, melt compression, injection, 3D printing, and a combination of two or more of them. The method of claim 5,
In the step (a2), the output is performed to have one pore shape selected from the group consisting of a square, a hexagon, an octagon, and a combination of two or more of them. The method of claim 5,
In the step (a2), the output is performed to satisfy at least one of the following conditions, a method of manufacturing a membrane for periodontal regeneration:
(i) 0.1 to 1 mm thick;
(ii) 0.1~0.5mm of pore wall width;
(iii) Average pore size 0.1~5mm. The method of claim 5,
In the step (a3), the cooling is performed for 1 to 30 minutes at a temperature of room temperature (25° C.) or less, a method of manufacturing a membrane for periodontal regeneration. The method of claim 1,
The natural polymer resin is one selected from the group consisting of collagen, chitosan, hyaluronic acid, carboxymethylcellulose, heparan sulfate, dextran, alginate, and a combination of two or more of them, a method for producing a membrane for periodontal regeneration. The method of claim 1,
The (B) step comprises the following steps, a method for producing a membrane for periodontal regeneration:
(b1) laminating a second polymer film including the first polymer film and a natural polymer resin;
(b2) heating the product of step (b1) to 30 to 80°C;
(b3) bonding the product of step (b2) at a pressure of 3 to 30 mPa; And
(b4) cooling the product of step (b3) for 1 minute to 3 hours. The method of claim 12,
In the step (b1), the lamination is a method of manufacturing a membrane for periodontal regeneration, in which at least one first polymer film and at least one second polymer film are intersected to each other to be stacked in two or more layers. The method of claim 12,
After step (b4),
(b5) cutting the product of step (b4) into a predetermined shape; And
(b6) packing the product of step (b5) after sterilization; further comprising, a method for producing a membrane for periodontal regeneration. A membrane for periodontal regeneration prepared by the method of any one of claims 1 to 14.

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