JP7220852B2 - Membrane for GBR - Google Patents

Description

TECHNICAL FIELD The present invention relates to a membrane suitable for use in guided bone regeneration (GBR) in dental treatment.

In implant medicine, a special hole is made in the alveolar bone at the position where the artificial tooth is to be attached, and the implant body is embedded in it, in order to replace the tooth that the patient has lost with an artificial tooth. There are cases in which the bone tissue of the alveolar bone is deficient due to periodontal disease or a long period of time since tooth loss.

When the bone tissue of the alveolar bone is thus deficient, a guided bone regeneration method (GBR method), for example, is used as a medical technique to promote regeneration of the bone tissue and obtain a sufficient bone volume for embedding the implant body. ing. This is a technique of covering alveolar bone with deficient bone tissue with a dedicated membrane to secure a space necessary for regeneration of new bone so that tissue cells such as gingiva do not enter the deficient portion.

Here, as the membrane used in the GBR method, a nonwoven fabric made of a material that can be decomposed and absorbed in vivo is also used so that a secondary surgical removal operation is not required. It is For example, Patent Document 1 proposes a membrane for GBR comprising a bioabsorbable film comprising an L-lactide/glycolide/ε-caprolactone terpolymer. This GBR membrane is composed of a single-layer film on the entire surface, and has average flexibility and strength on the entire surface.

JP 2012-024384 A

In addition to the above-mentioned biodegradability, the present invention has a strength that allows the site covering the new bone formation part to have sufficient space maintenance properties, and at the same time, when covering the alveolar bone, it is in contact with the surroundings of the new bone formation part. It is an object of the present invention to provide a GBR membrane having sufficient flexibility in the membrane periphery.

The present invention provides a first nonwoven fabric portion made of a biodegradable polymer that may contain 50 wt% or less of calcium phosphate, and at least one 50 wt. and a second nonwoven fabric portion made of a biodegradable polymer that may contain calcium phosphate of up to is.

The membrane for GBR of the present invention, with the above configuration, satisfies all of the requirements of biodegradability, space maintenance of the covered portion of the new bone formation part, and flexibility of the peripheral portion of the membrane in contact with the new bone formation part. is.

(b) is a perspective view showing an example of the membrane 1 for GBR of the present invention, and (a) is an assumed state in which the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are separated for explanation. It is a perspective view. FIG. 4 is a cross-sectional view showing a state in which an alveolar bone 51 and gingiva 53 at a treatment target position are incised. FIG. 4 is a cross-sectional view showing a state in which the membrane for GBR of the present invention is applied to the alveolar bone 51 at the treatment target position. FIG. 4 is a cross-sectional view showing how new bone is regenerated. 4 is a cross-sectional view showing a state in which an implant body 55 is embedded and an artificial tooth 61 is attached. FIG. 1 is a graph showing the results of an evaluation test of space retention properties of GBR membrane 1 of Example 1 and the membrane of Comparative Example 1. FIG. 2 is a graph showing blood permeability evaluation test results of GBR membranes 1 and 2 of Examples 1 and 2. FIG. 1 is a graph showing the results of an evaluation test of the tissue cell barrier performance of GBR membranes 1 to 3 of Examples 1 to 3 and the membrane of Comparative Example 1. FIG. 2 is a graph showing the results of an evaluation test of the BSA permeability of GBR membranes 2 and 3 of Examples 2 and 3. FIG. FIG. 2 is a diagram showing the relationship between membrane thickness and basis weight of membranes obtained in Examples and Comparative Examples.

The present invention provides a first nonwoven fabric portion made of a biodegradable polymer that may contain 50 wt% or less of calcium phosphate, and at least one 50 wt. and a second nonwoven fabric part made of a biodegradable polymer that may contain calcium phosphate of up to membrane.

The GBR membrane of the present invention having such a structure decomposes in the oral cavity over time.

The second nonwoven fabric part is in a state of being laminated on the substantially central part of the first nonwoven fabric part, but since the second nonwoven fabric part has a smaller area than the first nonwoven fabric part, the membrane for GBR of the present invention has an outer peripheral portion consisting only of the first nonwoven fabric portion and a central portion in which the first nonwoven fabric portion and the second nonwoven fabric portion are laminated when viewed from the normal direction to the surface. . For this reason, since the peripheral portion has flexibility, it has high adhesion to the alveolar bone, and since the central portion has high strength, it is excellent in space maintenance of the new bone formation portion.

In the GBR membrane of the present invention, the average pore size of the entire membrane, that is, the first nonwoven fabric portion and the second nonwoven fabric portion in a laminated state, is preferably 20 μm or less, and preferably 0.01 to 20 μm. more preferably 0.1 to 15 μm. The membrane for GBR of the present invention has tissue cell impermeability so as not to inhibit new bone regeneration, and the average pore size of the first nonwoven fabric portion and the second nonwoven fabric portion in the laminated state is adjusted as described above. This characteristic can be ensured more reliably by setting it to a range.

On the other hand, since the membrane for GBR of the present invention is entirely composed of non-woven fabric, the permeability of nutrient components for bone cell growth is ensured.

In the GBR membrane of the present invention having such a configuration, the outer peripheral portion consisting of only the first nonwoven fabric portion is arranged around the alveolar bone, which requires flexibility, and the first nonwoven fabric portion and the second nonwoven fabric portion are arranged. The central part, which has a laminated structure, is placed in the new bone formation part that requires space maintenance. should be optimized for For example, the area ratio of the second nonwoven fabric portion to the first nonwoven fabric portion is preferably 10 to 90%, more preferably 20 to 75%.

The basis weight of the portion of the membrane for GBR of the present invention in which the first nonwoven fabric portion and the second nonwoven fabric portion are integrated is preferably 150 to 650 g/m ² , more preferably 150 to 450 g/m ² . is more preferable. Here, the basis weights of the first nonwoven fabric part and the second nonwoven fabric part may be different as long as the above conditions are satisfied. can be higher.

This basis weight is a value in a state where the first nonwoven fabric portion and the second nonwoven fabric portion are integrated, and the membrane for GBR of the present invention is obtained by laminating the first nonwoven fabric portion and the second nonwoven fabric portion. When manufactured through a process of integration, the basis weight of the first nonwoven fabric portion and the second nonwoven fabric portion before lamination may be lower than this value.

The film thickness of the GBR membrane of the present invention is preferably 250 to 650 μm, more preferably 300 to 600 μm. This film thickness is the value at the portion where the first nonwoven fabric portion and the second nonwoven fabric portion are integrated, and the membrane for GBR of the present invention is the first nonwoven fabric portion and the second nonwoven fabric portion. is manufactured through a process of laminating and integrating, the film thickness of the laminated body before the integration may be larger than this value. Here, the film thicknesses of the first nonwoven fabric portion and the second nonwoven fabric portion may be different.

In addition, since the membrane for GBR of the present invention is in a state in which the second nonwoven fabric portion is laminated approximately in the central portion of the first nonwoven fabric portion, the second nonwoven fabric portion is laminated on the first nonwoven fabric portion. Depending on the manufacturing method of the membrane for GBR of the present invention, the thickness of these regions may be the same or one of them may be larger than the other.

For example, the thickness of the portion of the first nonwoven fabric part where the second nonwoven fabric part is to be laminated is adjusted to be smaller than the thickness of the other parts, and then the second nonwoven fabric part is provided. The film thickness of the regions with and without the second nonwoven fabric portion may be the same.

The first nonwoven fabric portion and/or the second nonwoven fabric portion in the membrane for GBR of the present invention preferably contains 50 wt% or less of calcium phosphate, and both the first nonwoven fabric portion and the second nonwoven fabric portion contain 50 wt%. It is more preferable to contain the following calcium phosphate. Such calcium phosphate is preferably, for example, β-phase calcium phosphate (β-TCP) or non-calcined hydroxyapatite (HA).

By containing 50% by weight or less of calcium phosphate in the first nonwoven fabric part and/or the second nonwoven fabric part, the first nonwoven fabric part and/or the second nonwoven fabric part are made hydrophilic. There is an advantage that the average pore size can be easily reduced.

Such calcium phosphate may be added to the biodegradable polymer in advance and then spun to be contained inside the polymer of the biodegradable polymer fiber, or may be attached to the fiber surface after the biodegradable polymer fiber is prepared. good too.

The fiber diameters of the fibers constituting the first nonwoven fabric portion and the second nonwoven fabric portion in the membrane for GBR of the present invention are preferably 0.1 to 100 μm. By using a nonwoven fabric having such a fiber diameter, sufficient permeability of nutrients for osteocyte growth in the blood is ensured. For example, as an example of nutrient permeability, the portion where the first nonwoven fabric part and the second nonwoven fabric part are integrated has the permeability of bovine serum-derived albumin (BSA), which is a kind of protein. indicates

In addition, setting the fiber diameter of the nonwoven fabric used in the present invention within this range is advantageous in terms of the productivity of the nonwoven fabric.

The portion of the membrane for GBR of the present invention in which the first nonwoven fabric portion and the second nonwoven fabric portion are integrated preferably has a bending strength of 1N or more. When such a membrane for GBR is used, the space maintainability of the newly formed bone formation part is sufficiently ensured.

The GBR membrane of the present invention is preferably produced by separately preparing the first nonwoven fabric portion and the second nonwoven fabric portion, laminating them, and integrating them by hot pressing.

In the GBR membrane of the present invention thus obtained, both the first nonwoven fabric portion and the second nonwoven fabric portion are laminated and compressed by hot pressing. As a result, the average pore size of the nonwoven fabric is reduced to 20 μm or less to prevent tissue cells such as soft tissue from invading the new bone formation part while maintaining the permeation performance of nutrients for bone cell growth. Easy to do.

That is, for example, in a non-woven fabric that has been melt-blown or dry-spun, the fibers are piled up and there is a distance between the fibers in the thickness direction. requires. On the other hand, as the thickness of the nonwoven fabric increases, the softness decreases. On the other hand, when the laminate is integrated by heat pressing, the fibers constituting the nonwoven fabric are deformed in the direction of flattening, and the distance between the fibers in the thickness direction is shortened, and the average pore size can be reduced. can. When the first nonwoven fabric and/or the second nonwoven fabric are hydrophilized using calcium phosphate as described above, the average pore size of the nonwoven fabric can be further reduced. Such hydrophilization methods include, for example, alternate immersion and hydrophilization by excimer treatment.

The membrane for GBR of the present invention comprises a first nonwoven portion made of a biodegradable polymer and a second nonwoven portion made of a biodegradable polymer.

Various biodegradable polymers can be used in the GBR membrane of the present invention as long as they do not impair the effects of the present invention. Selected as appropriate. Such biodegradable polymers are preferably aliphatic polyesters, and more preferably polylactic acid, polyglycolic acid, polyε-caprolactone, or copolymers thereof. Among them, a copolymer (PLGA) having a composition ratio of lactic acid and glycolic acid of 80:20 to 95:5 is preferable.

The membrane for GBR of the present invention has a non-woven fabric part "composed of a biodegradable polymer", but this term means that it is substantially composed of a degradable polymer and does not contain trace components such as physiologically active substances. not excluded.

Hereinafter, representative embodiments of the membrane for GBR of the present invention will be described in detail with reference to the drawings. However, each drawing is for conceptually explaining the present invention, and the present invention is not limited to what is illustrated.

1. Overview of the GBR membrane 1 of the present invention The GBR membrane 1 of the present embodiment is a medical device used for dental treatment, and is used for, for example, the alveolar bone 51 in which bone tissue defects have occurred by guided bone regeneration ( When implant treatment or the like is performed using Guided Bone Regeneration (GBR method), by covering the bone tissue defect portion of the alveolar bone 51 (herein also referred to as “new bone formation portion”), tissue such as gingiva It prevents cells from invading bone tissue defects and assists in the guided regeneration of new bone.

As shown in FIGS. 1(a) and 1(b), the GBR membrane 1 of this embodiment is composed of a first nonwoven fabric portion 3 and one second nonwoven fabric portion 5. It has a structure in which the nonwoven fabric part of is integrated. In this embodiment, the shapes of the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are substantially rectangular, but the shapes are not limited to this, and the shapes are optimized according to the therapeutic requirements. is desirable.

2. Details of first non-woven fabric part 3 and second non-woven fabric part 5 The first non-woven fabric part 3 and the second non-woven fabric part 5 are formed in a substantially rectangular shape using a biodegradable polymer that degrades in the oral cavity over time. It is The first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 have substantially similar shapes with different areas, and the second nonwoven fabric portion 5 has a smaller area than the first nonwoven fabric portion 3. there is

As the biodegradable polymer used for forming the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5, for example, a copolymer of lactic acid and glycolic acid is used. The biodegradable polymer is spun, for example, by meltblowing (MB) or dry spinning (DSP) to form a nonwoven fabric. Here, the dry spinning method is, for example, as described in Japanese Patent Application Publication No. 2013-534978, dissolving a polymer in a volatile solvent and injecting it into a high-speed gas stream such as compressed air to form a polymer strand. , and a method of stretching this with a high-speed gas flow.

Further, it may be hydrophilized by alternate immersion or excimer treatment. Alternatively, the first nonwoven portion 3 and the second nonwoven portion 5 may be doped with calcium phosphate, such as beta-phase calcium phosphate (β-TCP) or uncalcined hydroxyapatite (HA).

The fiber diameter is preferably in the range of approximately 0.1 to 100 μm by spinning using the melt blowing method or the dry spinning method.
Furthermore, it is preferable that the average pore diameter of the entire membrane in the laminated state is 20 μm or less.

The basis weight of the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 is preferably in the range of 10 to 450 g/m ² , more preferably 150 to 350 g/m ² in both, and 250 in both. Most preferred is ˜350 g/m ² .

In Embodiment 1, the first nonwoven fabric portion 3 is 80 g/m ² and the second nonwoven fabric portion 5 is 80 g/m ² (the basis weight of the laminated/integrated portion is higher than these values). ). Thus, by making the first nonwoven fabric portion 3 have a low basis weight, the flexibility of the first nonwoven fabric portion 3 can be enhanced.

^The membrane for GBR of the present invention preferably has a film thickness in the range of 250 to 650 μm as described above. However, it is even more preferable to satisfy the following formulas (1) and (2).
1.6X-200 ≤ Y ≤ 1.6X + 100 (1)
150≤X≤450 (2)

Moreover, the area of the second nonwoven fabric portion 5 with respect to the first nonwoven fabric portion 3 is preferably in the range of approximately 20 to 75%.

As a result, the GBR membrane 1 of this embodiment, which is formed using the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5, is resistant to the alveolar bone 51 due to the flexibility of the outer peripheral portion composed only of the first nonwoven fabric portion 3. Adhesion is high, and at the same time, the strength of the central portion where the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are laminated and integrated makes it possible to maintain the space of the new bone formation portion that regenerates the new bone. Good. In addition, it is desirable that the bending strength of the central portion is 1 N or more.

In addition, due to the flexibility of the peripheral part due to the above configuration, when using the GBR membrane 1 in this embodiment, the first nonwoven fabric part 3 located in the outer peripheral part can be trimmed according to the shape of the alveolar bone 51 and the treatment space. It becomes easier and the workability is improved.

3. Lamination of first nonwoven fabric portion 3 and second nonwoven fabric portion 5 In the GBR membrane 1 of the present invention, when viewed from the normal direction (the direction of the arrow in FIG. 1(a)) to the surface thereof, The first non-woven fabric part 3 and the second non-woven fabric part 5 are substantially centered, and the second non-woven fabric part 5 is formed in the central part so that the outer peripheral part where only the first non-woven fabric part 3 is present is secured. Although the two nonwoven fabric portions 5 are laminated, in the present embodiment, the separately prepared first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are heat-pressed under predetermined conditions. Manufactured by solid integration.

The conditions used for the hot press may be appropriately adjusted within a range that does not impair the effects of the present invention, and are preferably such that the degree of crystallinity of the fiber does not change before and after the hot press. For example, it is preferable to set a load of 70 to 350 g/cm ² , a press holding time of 10 to 60 seconds, and a temperature of 60 to 120°C.

In addition, the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 do not necessarily have to be one each. The second nonwoven fabric portion 5 may be laminated. By using a membrane for GBR having a plurality of second non-woven fabric parts, space maintenance is adjusted by increasing the bending strength of the central part according to the condition of the new bone formation part and the surrounding gingiva 53. You may

In this embodiment, the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are laminated and hot-pressed for integration, whereby the nonwoven fabrics are compressed to have an average pore size of approximately 20 μm or less. there is As a result, it is possible to suitably prevent tissue cells such as soft tissue from invading the space of the new bone formation part while maintaining the blood permeability and the permeability of nutrients for bone cell growth.

The configuration of the membrane for GBR of the present invention has a structure in which the first nonwoven fabric portion 3 and the second nonwoven fabric portion 5 are integrated. It does not exclude the lamination of a third layer as appropriate, such as when reinforcing strength.

4. Method of Using the GBR Membrane 1 of the Present Embodiment Next, a method of implant treatment using the GBR membrane 1 of the present embodiment will be described in detail with reference to FIGS. 2 to 5. FIG. 2 to 5 are diagrams showing the treatment flow of implant treatment using the present membrane 1 for GBR.

Specifically, FIG. 2 is a cross-sectional view showing a state in which the alveolar bone 51 and the gingiva 53 at the treatment target position are incised, and FIG. 3 is a state in which the present GBR membrane 1 is applied to the alveolar bone 51 at the treatment target position. FIG. 4 is a cross-sectional view showing a state in which new bone is regenerated in a new bone-forming part, and FIG. 5 is a cross-sectional view showing a state in which an implant body 55 is embedded and an artificial tooth 61 is attached. is.

<Step of incising gingiva 53>
When performing implant treatment, if the alveolar bone 51 to which the implant body 55 is to be embedded has lost bone tissue due to bone resorption or the like caused by the release of calcium, it is necessary to regenerate new bone at the missing position of the alveolar bone 51. There is

Therefore, as shown in FIG. 2, first, the gingiva 53 covering the alveolar bone 51 in which the implant body 55 is to be embedded is incised using a medical instrument such as a scalpel, and a treatment space for applying the GBR membrane 1 to the alveolar bone 51 is secured. . It may not be necessary to perform the incision step depending on the time elapsed after the patient's original tooth has fallen out, the situation in which the new bone is to be regenerated, such as when the implant body 55 has already been implanted.

<Application process of membrane 1 for GBR>
Next, the GBR membrane 1 of this embodiment is applied to the alveolar bone 51 . After preparing the bone filling material 63 by collecting autogenous bone from the chin, mandibular limb, tibia, hipbone, etc. in advance, the blood adhering to the new bone formation part, the alveolar bone 51, the gingiva 53, etc. is removed. After washing, a bone grafting material 63 is filled into the new bone-forming part.

Subsequently, as shown in FIG. 3 , the GBR membrane 1 of the present embodiment is covered and fixed to the alveolar bone 51 while conforming to the surface shape of the alveolar bone 51 . Although it depends on the shape of the alveolar bone 51 and the position of the treatment, if there is a concern that the GBR membrane 1 may be misaligned after the treatment, a separately prepared fixing pin 65 is used to assist and fix the membrane 1 more firmly. It is desirable to The fixing pin 65 is driven into the alveolar bone 51 while avoiding the newly formed bone formation portion.

<Standby process associated with new bone regeneration>
After confirming the fixation of the membrane 1 for GBR of the present embodiment, as shown in FIG. Wait until the new bone is regenerated in the created area.

Although the rate of new bone regeneration differs from patient to patient, it generally takes about 4 to 6 months. At this time, it is necessary to be careful not to apply excessive stimulation or the like to the surgical site.

<Process of Embedding Implant 55 and Attaching Artificial Tooth 61>
After waiting until the new bone is regenerated, the implant body 55 is embedded in the alveolar bone 51.例文帳に追加More specifically, first, the gingiva 53 is incised again, a hole is made in the alveolar bone 51 after regeneration of new bone using a medical drill (not shown), and the implant body 55 is embedded in the hole. A temporary cover is attached to the implant body 55, and the gingiva 53 is closed and sutured.

In addition, since the GBR membrane 1 of the present embodiment is completely decomposed after a predetermined time has passed, there is no need to take out the present GBR membrane 1 again.
After the above steps, wait about three to four months, and after the implant body 55 and the alveolar bone 51 are bonded together, the preformed artificial tooth 61 is attached to the implant body 55 .
This completes the implant medical treatment using the GBR membrane 1 according to the present embodiment.
Although the embodiments of the present invention have been described above with reference to the drawings, the present invention is not limited to these embodiments.

In this embodiment, a first nonwoven fabric and a second nonwoven fabric are separately prepared, laminated, and then hot-pressed to integrate them into a first nonwoven fabric portion and a second nonwoven fabric portion. was prepared, the first nonwoven portion and the second nonwoven portion can also be prepared by a series of nonwoven manufacturing steps. For example, after a first nonwoven portion is prepared by electrospinning or melt spinning, a second nonwoven portion is prepared thereupon by electrospinning or melt spinning continuously to a narrower extent. It is a way to

<<Example 1>>
A GBR membrane 1 having the structure shown in FIG. 1 was produced.
First, using PLGA with a composition ratio of lactic acid (LA) and glycolic acid (GA) of 88 (LA):12 (GA), a nonwoven fabric (fiber diameter: about 10 μm) was produced by the melt blow method, and this was first Nonwoven fabric and second nonwoven fabric. All of them have a basis weight of 80 g/m ² .

The first nonwoven fabric and the second nonwoven fabric obtained as described above are laminated and pressed under the conditions of 85° C., 30 seconds and 300 g/cm ² to integrate them to form the membrane 1 for GBR of the present invention. Obtained.

In the GBR membrane 1 thus obtained, the first nonwoven fabric corresponds to the first nonwoven fabric part of the present invention, and the second nonwoven fabric corresponds to the second nonwoven fabric part of the present invention. Such a correspondence relationship also applies to the following examples.

In this example, nonwoven fabrics having the same basis weight but different sizes were laminated, but the first and second nonwoven fabrics may differ in one or more of the polymer component, fiber diameter, and basis weight.

<<Example 2>>
The GBR membrane 1 obtained in Example 1 was immersed in a CaCl ₂ /Tris-HCl (200 mM) aqueous solution and then rinsed with pure water, further immersed in a Na ₂ HPO ₄ aqueous solution (120 mM) and then rinsed with pure water. This process was defined as one cycle, and this cycle was repeated 10 times to obtain the membrane 2 for GBR of the present invention, which was hydrophilized by depositing hydroxyapatite on the surface of the fiber.

<<Example 3>>
A GBR membrane having the structure shown in FIG. 1 was produced.
First, PLGA and non-calcined hydroxyapatite (HA) having a composition ratio of lactic acid (LA) and glycolic acid (GA) of 82 (LA): 18 (GA) were used, and a nonwoven fabric (fiber diameter: about 1 μm) was formed by a dry spinning method. ), which was used as the first nonwoven fabric and the second nonwoven fabric. All of them had a basis weight of about 150 g/m ² and a weight ratio of PLGA and HA of 85:15.

The first nonwoven fabric and the second nonwoven fabric obtained as described above are laminated and pressed at 85° C. for 30 seconds at 300 g/cm ² using a spacer of 300 μm to integrate the thickness. A GBR membrane 3 of the present invention having a thickness of about 300 μm was obtained.

<<Example 4>>
A GBR membrane 4 was produced in the same manner as in Example 3, except that the thickness of the spacer used in the hot press of Example 3 was changed to 400 μm. The thickness of the resulting GBR membrane 4 was about 400 μm.

<<Example 5>>
A GBR membrane 5 was produced in the same manner as in Example 3, except that the thickness of the spacer used in the hot press of Example 3 was changed to 500 μm. The thickness of the resulting GBR membrane 5 was about 500 μm.

<<Example 6>>
A GBR membrane 6 was prepared in the same manner as in Example 3, except that each of the first nonwoven fabric and the second nonwoven fabric in Example 3 had a basis weight of about 100 g/m ² . The thickness of the obtained GBR membrane 6 was about 300 μm.

<<Example 7>>
The GBR membrane 7 was prepared in the same manner as in Example 3 except that the basis weight of the first nonwoven fabric and the second nonwoven fabric of Example 3 was changed to about 200 g/m ² and the thickness of the spacer used in the hot press was changed to 600 µm. Created. The thickness of the obtained GBR membrane 7 was about 600 μm.

<<Example 8>>
A GBR membrane 8 was prepared in the same manner as in Example 3, except that the weight ratio of PLGA and HA in Example 3 was changed to 100:0. The thickness of the resulting GBR membrane 8 was about 300 μm.

<<Example 9>>
A GBR membrane 9 was prepared in the same manner as in Example 3, except that the weight ratio of PLGA and HA was changed to 70:30. The thickness of the resulting GBR membrane 9 was about 300 μm.

<<Example 10>>
A GBR membrane 10 was produced in the same manner as in Example 3, except that HA in Example 3 was changed to β-TCP. The thickness of the resulting GBR membrane 10 was about 300 μm.

<<Example 11>>
The GBR membrane 11 was prepared in the same manner as in Example 3 except that the PLGA of Example 3 was changed to PLGA having a composition ratio of lactic acid (LA) and glycolic acid (GA) of 88 (LA): 12 (GA). Created. The thickness of the resulting GBR membrane 11 was about 300 μm.

<<Example 12>>
The GBR membrane 12 was prepared in the same manner as in Example 3 except that the PLGA of Example 3 was changed to PLGA having a composition ratio of lactic acid (LA) and glycolic acid (GA) of 85 (LA): 15 (GA). Created. The thickness of the resulting GBR membrane 12 was about 300 μm.

<<Comparative Example 1>>
"Gore-Tex TR Membrane" (Gore-Tex) manufactured by Japan Gore-Tex Co., Ltd. was used as a comparative membrane. This is a non-absorbent membrane in which a sheet-like skeleton material of titanium is arranged on an expanded polytetrafluoroethylene film. , the difference in strength depending on the part is provided.

<<Comparative Example 2>>
A non-woven fabric (fiber diameter: about 1 μm) was formed by dry spinning using PLGA with a composition ratio of lactic acid (LA) and glycolic acid (GA) of 82 (LA):18 (GA) and non-calcined hydroxyapatite (HA). was produced, and this was used as the first nonwoven fabric and the second nonwoven fabric. All of them had a basis weight of about 150 g/m ² and a weight ratio of PLGA and HA of 85:15.

The first nonwoven fabric and the second nonwoven fabric thus obtained are laminated and integrated by hot pressing using a spacer of 200 μm under the conditions of 85° C., 30 seconds and 300 g/cm ² to obtain a thickness. A membrane of approximately 200 μm was obtained. The resulting membrane was melted and did not retain its fibrous structure. This is considered to be due to the effect of high pressure due to compression to a thinner film thickness than in each example.

<<Comparative Example 3>>
A membrane was produced in the same manner as in Comparative Example 2, except that the thickness of the spacer used in the hot press of Comparative Example 2 was changed to 600 μm. The thickness of the obtained membrane was about 600 μm.

<<Comparative Example 4>>
A membrane was prepared in the same manner as in Comparative Example 2, except that each of the first and second nonwoven fabrics of Comparative Example 2 had a basis weight of about 50 g/m ² . The thickness of the obtained membrane was about 300 μm.

<<Comparative Example 5>>
A membrane was prepared in the same manner as in Comparative Example 2, except that each of the first nonwoven fabric and the second nonwoven fabric in Comparative Example 2 had a basis weight of about 250 g/m ² and the thickness of the spacer used in the hot press was changed to 500 μm. The thickness of the obtained membrane was about 500 μm. The resulting membrane was melted and did not retain its fibrous structure.

[Evaluation test]
(1) Evaluation of space retention For the GBR membranes of Examples 1 to 12 and the comparative membranes of Comparative Examples 1 to 4, the test specimen was bent upward on a flat plate and fixed at two points on the left and right. The load cell for load detection was lowered from the bottom at a constant speed, and the load detected when the strain was 10% was read. The sample was fixed with a membrane having a width of 22 mm with a distance between fixings of 15 mm so that the central portion was curved upward by 3 to 4 mm from the base. The load cell was lowered at 2 mm/min. The results are shown in FIG. 6 and Table 1.
From FIG. 6 and Table 1, it can be seen that the membrane for GBR of the present invention (for example, the pressed product in FIG. 6) is excellent in space retention.

(2) Evaluation of Blood Permeability The GBR membrane 1 of Example 1 and the GBR membrane 2 of Example 2 were subjected to a pressure test according to ASTM F2392-04. There was an opening with a diameter of 25 mm at the tip of the pipe line to be pressurized, and the test piece was set so as to cover the opening in a plane. Pig blood was pumped through the line, the pressure was increased, and the pressure was read from the pressure gauge when the blood permeated the membrane and the white membrane began to turn red with blood. Blood permeation pressure (mmHg) was measured under the conditions and method described above. The results are shown in FIG.
From FIG. 7, it can be seen that both the GBR membrane 1 and the GBR membrane 2 of the present invention are excellent in blood permeability, but the GBR membrane 2 subjected to hydrophilization treatment is particularly excellent in blood permeability. . This is suitable for more reliable distribution of serum proteins and minerals. On the other hand, the sample of Comparative Example 1 has no blood permeability.

(3) Evaluation of tissue cell barrier performance The average pore diameter of the GBR membranes 1 to 3 of Examples 1 to 3 and the comparative membrane of Comparative Example 1 was evaluated by the bubble point method (ASTM F316-86). . After allowing the sample to absorb a fluorinated solvent (trade name: Fluorinert FC-40) as a wetting liquid, the size of the test piece was pressurized to a circle with a diameter of 25 mm using Porometer 3G manufactured by Bell Japan Co., Ltd. Air pressure was applied from one surface side of the membrane to the other surface side, and the minimum pressure (bubble point) at which bubbles could be observed on the other surface side of the membrane was measured. The average pore size (μm) was calculated from a graph showing the pore size distribution of the nonwoven fabric based on the bubble point measurement results. The results are shown in FIG.
From FIG. 8, all of GBR membrane 1 (pressed product), GBR membrane 2 (press + alternate infiltration), and GBR membrane 3 (HA added before spinning) of the present invention have a small average pore size, and tissue cells It turns out that it is excellent in barrier performance.

(4) Evaluation of bovine serum-derived albumin (BSA) permeability The GBR membranes 2 and 3 of Examples 2 and 3 were evaluated for bovine serum-derived albumin (BSA) permeability. After cutting the wet membrane into a circle with a diameter of 25 mm, it was set in a Franz cell, a BSA/PBS solution was used on the donor side, and a PBS solution was used on the receptor side. Absorbance was measured using a visible spectrophotometer. The obtained absorbance was converted to the BSA concentration based on the calibration curve, and the transmittance (%) was calculated from the value. The results are shown in FIG. A permeability of 5% or more was determined to have permeability to bovine serum-derived albumin (BSA).
From FIG. 9, it was found that membranes 2 and 3 for GBR of the present invention have a BSA permeability of 5% or more, and are excellent in permeability of nutrients such as serum proteins and minerals for the growth of bone cells.

INDUSTRIAL APPLICABILITY The GBR membrane of the present invention is a medical device that has high workability and space maintenance properties and can be suitably used in guided bone regeneration in dentistry.

1 GBR membrane 3 First nonwoven fabric part 5 Second nonwoven fabric part 51 Alveolar bone 53 Gingiva 55 Implant body 61 Artificial tooth 63 Bone filler 65 Fixing pin

Claims (7)

a first nonwoven portion comprising a biodegradable polymer optionally containing up to 30 wt% calcium phosphate;
At least one biodegradable polymer that may contain calcium phosphate in an amount of 30 wt% or less, which has a smaller area than the first nonwoven fabric portion and is laminated in a substantially central portion of the first nonwoven fabric portion. a second nonwoven portion;
The biodegradable polymer constituting the first nonwoven fabric portion and the biodegradable polymer constituting the second nonwoven fabric portion both have a composition ratio of lactic acid and glycolic acid of 80:20 to 95:5. is a copolymer with
The fiber diameter of the fibers constituting the first nonwoven fabric portion and the fiber diameter of the fibers constituting the second nonwoven fabric portion are both 0.1 to 10 μm,
It has a structure in which the first nonwoven fabric part and the second nonwoven fabric part are integrated,
The basis weight (X) [g/m ² ] and the film thickness (Y) [μm] of the portion where the first nonwoven fabric part and the second nonwoven fabric part are integrated are given by the following formula (1), Both (2) and (3) are satisfied,
150≤X≤450 (1)
250≤Y≤650 (2)
1.6X-200≤Y≤1.6X+100 (3)
Membrane for GBR. The membrane for GBR according to claim 1, wherein the area ratio of the second nonwoven fabric portion to the first nonwoven fabric portion is 10 to 90%. 3. The membrane for GBR according to claim 1, having an average pore size of 20 [mu]m or less. 4. The membrane for GBR according to any one of claims 1 to 3 , wherein the first nonwoven part and/or the second nonwoven part contains 30 wt% or less of calcium phosphate. 5. The membrane for GBR according to any one of claims 1 to 4, wherein the part in which the first nonwoven fabric part and the second nonwoven fabric part are integrated has a bending strength of 1N or more. 6. The membrane for GBR according to any one of claims 1 to 5 , wherein the part having the structure in which the first nonwoven fabric part and the second nonwoven fabric part are integrated is permeable to bovine serum-derived albumin. 7. The membrane for GBR according to any one of claims 1 to 6, which is produced by laminating the first nonwoven fabric and the second nonwoven fabric and integrating them by hot pressing.

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