KR20160048741A - A material for tissue repair and apparatus for tissue repair employing the same - Google Patents

Abstract

Provided are a tissue repair material and a tissue repair device having the same. The tissue repair material includes a dissolved solidified material of polylactic acid, has a pillar shape with an average cross-sectional diameter of 0.08 to 0.5 mm extending in a length direction, and has an in vivo decomposition period of one or more years. The polylactic acid is crystalline poly-L-lactic acid, and the dissolved solidified material of the polylactic acid has a number average molecular weight of 30,000 or more. An in vivo decomposition period is long, so exhibition of effects may be maintained for a long time. Also, in vivo injection may be easily performed.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a tissue repair material,

TECHNICAL FIELD The present invention relates to a material for tissue repair and a device having the same, and more particularly, to a material for tissue recovery that can exhibit an effect for a long period of time due to a long period of decomposition in the body, and a tissue recovery device having the same.

In recent years, there has been a growing interest in restoration or enhancement of tissue for the purpose of healing facial defects, acne, scars of surgical procedures or defects or contours of soft tissues caused by aging.

As a result, a number of materials have been used extensively for the purpose of correcting defects in soft tissue, but for the present, no material is considered to be completely safe and effective.

In the past, a small amount of liquid silicone was used for the purpose of correcting small soft tissue defects with minimal physical stress at the prescription site. However, such liquid silicone migrated to body parts away from these implants, resulting in a variety of physiological and clinical problems. Accordingly, the FDA has prohibited the use of liquid silicon in humans for the above problems and misuse of liquid silicon.

On the other hand, in the 1970s, injectable bovine collagen became available, and it was attempted as an effective treatment for soft tissue defects. However, this collagen was reabsorbed into the body within 2 to 3 months, and the duration of treatment was considerably short. In addition, safety measures must be used to avoid allergic reactions to small proteins in collagen.

Thereafter, as new materials which can be used for restoration or enhancement of soft tissues and which can prevent the problems previously caused by using collagen and liquid silicone to some extent, biocompatible ceramic particles, thermoplastic materials, thermosetting materials Polymer blend and the like.

However, they are safe, injectable, long-lived in the human body, and do not exhibit sufficient properties as tissue restoration and growth materials exhibiting bioabsorbability.

Another object to be solved by the present invention is to provide a substance for tissue repair which is capable of exerting an effect for a long time due to a long period of decomposition in the body and is easily injected into the body.

A problem to be solved by the present invention is to provide a tissue recovery device comprising the tissue repairing material.

To solve these problems, according to one aspect of the present invention,

Characterized in that it comprises a molten solid of polylactic acid and has a columnar shape extending in the longitudinal direction and having an average cross sectional diameter of 0.08 to 0.5 mm,

Wherein the polylactic acid is crystalline poly-L-lactic acid, and the molten solid of the polylactic acid has a number average molecular weight of 30,000 or more.

The molten solidification of the polylactic acid may have a number average molecular weight of from 30,000 to 500,000.

The molten solidified product of the polylactic acid may be formed by heating and melting the polylactic acid at a temperature above melting point of the polylactic acid, and then injecting it into a mold or extruding it through a die.

According to another aspect of the present invention,

(a) an injection needle; And

(b) a tissue-restoring device including the tissue-restoring material inserted in the through-hole of the injection needle.

And a fixture for fixing the tissue repairing material to the outer surface of the injection needle.

The material for tissue repair according to an embodiment of the present invention is crystalline among polylactic acid. After the polylactic acid is melted and solidified to have a cylindrical shape, a molten solid of polylactic acid having a number average molecular weight of 30,000 or more It is easy to perform the procedure because it has a long period of decomposition in the body and can exert its effects for a long time and has a form that is easily injected into the body so that it can be accurately performed at a desired position.

In addition, the tissue repair material according to one embodiment of the present invention includes a molten solid of polylactic acid and has a columnar shape extending in the longitudinal direction and having an average cross-sectional diameter of 0.08 to 0.5 mm, There is no fear of the growth of microorganisms and bacteria after the smooth sterilization process, and there is little formation of internal pores, so that it can be uniformly decomposed for a long time.

The material for tissue repair according to an embodiment of the present invention is not injected into a solution such as water by dissolving it in a solvent such as water but has a columnar shape of the molten solidified polylactic acid, So that a desired amount can be accurately performed.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate preferred embodiments of the invention and, together with the description of the invention given below, serve to further the understanding of the technical idea of the invention, And should not be construed as limiting.
1A is a perspective view of a tissue repair material according to an embodiment of the present invention.
1B is a perspective view of a tissue repair material according to an embodiment of the present invention.
2 is a schematic diagram of a tissue recovery device according to an embodiment of the present invention.
3 is a schematic diagram of a tissue recovery device according to an embodiment of the present invention.
4 is a graph showing decomposition characteristics in the body of the materials for tissue repair according to Examples 1 to 5 and Comparative Example 1. Fig.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. Prior to this, terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms, and the inventor should appropriately interpret the concepts of the terms appropriately It should be construed in accordance with the meaning and concept consistent with the technical idea of the present invention based on the principle that it can be defined.

Therefore, the embodiments described in the present specification and the configurations shown in the drawings are only the most preferred embodiments of the present invention and do not represent all the technical ideas of the present invention. Therefore, It is to be understood that equivalents and modifications are possible.

Hereinafter, the present invention will be described in detail.

The tissue-repairing material according to one aspect of the present invention has a decomposition period of 1 year or more, preferably 1 to 15 years, more preferably 1 to 10 years, even more preferably 2 to 4 years in the body . The polymer constituting the material for tissue repair of the present invention has a duration of more than one year in the body and collagen or hyaluronic acid gel used as an implant which has been implanted subcutaneously or in the skin for conventional cosmetic surgery or restoration operation, Can be resorbed very quickly within one to six months each, thereby solving the problem unsuitable for plastic surgery.

Biocompatible polymers having a biodegradation period of 6 months or less in the body can induce collagen tissue formation in the skin to exert the effect of the filler. However, since the duration of the effect is not long compared with the existing hyaluronic acid formulations, I do not. The short duration can be a fatal drawback, as healthcare professionals with fillers see safety as an important indicator of filler selection as a very important indicator.

The tissue-repairing material according to one aspect of the present invention comprises a molten solid of polylactic acid and has a columnar shape having an average cross-sectional diameter of 0.08 to 0.5 mm extending in the longitudinal direction, Wherein the polylactic acid is crystalline poly-L-lactic acid and has a number average molecular weight of 30,000 or more.

Since collagen synthesis, which plays a role of tissue repair in the body, is known to proceed with the biodegradation reaction of polylactic acid, in order to exhibit the tissue repair effect over a long period of 1 year or more, It is required to provide a material for tissue repair.

The inventors of the present invention have found that the molecular weight and distribution of polylactic acid as a material thereof, crystallinity and crystal structure, shape and porosity of a tissue-recovering material are degraded Which is a key factor in determining

The polylactic acid used as the material for the tissue repair material has excellent thermal processing characteristics in addition to the environmentally friendly, biocompatible, and resource-saving properties commonly possessed by the biodegradable polymer, as compared with other biopolymers. It is an FDA-approved substance that can be used for direct contact with the body's physiological fluids.

Polylactic acid is a polyester synthesized by condensation polymerization of lactides. The lactide, which is a polymerization raw material, is mainly obtained from potato and corn, and contains natural vegetable sugar components such as corn syrup Is used as a raw material. Due to these properties, polylactic acid has been used in biodegradable suture materials and orthopedic implants for more than 30 years and has proven its safety.

Polylactic acid can also be applied to controlled-release medicinal materials or artificial skin. In vivo, polylactic acid is decomposed by hydrolysis, releasing the drug at the same time, and once it is decomposed, it is left as lactic acid, which is metabolized to H ₂ O and CO ₂ , which are completely harmless to human body.

Polylactic acid has L-, D-, and D- and L-type stereoisomers and is commercially available as L-type poly-L-lactic acid (PLLA) , L-lactic acid is produced.

Among them, poly-L-lactic acid (PLLA, Poly-L-lactic acid) is a crystalline resin having a melting point of 180 ° C. On the other hand, it is known that D, L-type poly D, L-lactic acid is considerably amorphous and decomposes rapidly in the body. Polylactic acid present in vivo is an L isomer, and polylactic acid (PLLA) having high crystallinity is used as a skin cosmetic filler material.

Therefore, in the present invention, in order to exhibit the tissue repairing ability as much as possible for maintaining the decomposition period in the body for a long period of more than one year as a tissue repairing material, polylactic acid having excellent biocompatibility and high crystallinity - Use lactic acid (PLLA).

The poly-L-lactic acid used in the tissue repair material of the present invention maintains and maintains its shape without being reabsorbed in the body for more than one year in the subcutaneous tissue or skin to be inserted for the procedure, Fibrosis constituting the fibrous tissue is formed, and a tissue restoration function such as a beauty filler for wrinkle removal can be performed.

At this time, poly-L-lactic acid does not have only 100% L-type but may still have crystallinity even if it contains about 15% of D-type. Therefore, the poly-L-lactic acid as referred to in the present invention means a crystalline polylactic acid of 100% L type or a polylactic acid mixed with L-type and D-type containing up to 15% of D-type.

In addition, the material for tissue repair of the present invention is formed by melting and heating the polylactic acid at a temperature above the melting point, molding the polylactic acid by various methods, cooling it, and solidifying it, that is, using molten solidification.

For example, the molten solidified product of polylactic acid may be formed by melting and melting the polylactic acid at a melting point or higher, then injecting it into a mold having a predetermined shape, or extruding it through a die.

Alternatively, conventionally, a step of dissolving polylactic acid in an organic solvent, followed by spinning in a wet process, and then solidifying the polylactic acid to prepare a polylactic acid in the form of a solid column has been used. However, the solid product of polylactic acid produced by the wet process necessarily undergoes the process of discharging the organic solvent during the solidification process, and a lot of pores are formed in the process of discharging the solvent to the outside, It has no choice but to take shape. As a result, the resulting polylactic acid solids accelerate the decomposition of defects such as pores present on the surface and inside thereof. Furthermore, since the removal of the organic solvent used for processing is not accomplished completely, if the organic solvent is used as a material for tissue repair, the residual organic solvent may cause side effects in the body.

A method of molding the polylactic acid raw material itself into a predetermined shape by a milling machine or the like may also be considered, but there may still be problems such as productivity, uniformity of the obtained shape, and contamination of the manufacturing process .

On the other hand, since the material for tissue repair of the present invention contains molten solidified material of polylactic acid, it does not require a process such as discharge of solvent, and its surface is smooth, and there is no defect that microorganisms and bacteria will grow after sterilization process , There is almost no pore formation in the interior of the pores, and the problem of accelerating the decomposition in the pore portions does not occur, the whole area is uniformly decomposed, and the duration in the body can be remarkably increased.

As described above, since the tissue repair material of the present invention has a smooth surface, fibroblast, which is an important component of the fibrous connective tissue, promotes adherence to the surface of the tissue repair material, There is an advantage of accelerating the synthesis.

On the other hand, when the polylactic acid is heated and melted at a temperature above the melting point and then molded into a column shape using a mold or a die, the polylactic acid is melted by heating the polylactic acid in a molten state under various influences such as temperature, time, It is known that molecular weight reduction due to decomposition may occur.

Accordingly, in order to solve the problem of decreasing the molecular weight during the melting and solidification of polylactic acid, the present invention uses a polylactic acid having a high molecular weight before melting to prepare a material for tissue repair.

That is, the polylactic acid constituting the material for tissue repair may have a number-average molecular weight of 50,000 or more, preferably 50,000 to 700,000, more preferably 100,000 to 500,000, and a number-average molecular weight of 30,000 or more after melt- Should be from 30,000 to 500,000, and more preferably from 50,000 to 300,000.

When the number average molecular weight of the polylactic acid satisfies the above range, even if the decrease in the molecular weight is minimized or the molecular weight of diarrhea is reduced during the process of preparing the columnar shape through the melting and solidifying process, The substance to be dosed can be a relatively high molecular weight substance, and the duration of the tissue-recovering substance in the body may be one year or more.

The tissue repair material according to an embodiment of the present invention has a cross section of a predetermined shape and extends in the longitudinal direction to have a columnar shape. Referring to FIGS. 1A and 1B, And various other forms are possible. Particularly, in the case of the circular column shape, it is the most preferable form for injection into the body through the needle.

As described above, since the tissue-repairing material of the present invention has a columnar shape rather than a microparticle shape, it is easy to inject through a needle or the like, and the injection amount can also be controlled by controlling the length.

The average cross-sectional diameter of the material for tissue repair may be adjusted to such an extent that injection through the injection needle is possible, for example, 0.08 to 0.5 mm, preferably 0.1 to 0.4 mm, more preferably 0.15 to 0.3 mm.

Wherein the tissue supporting material has an average cross-sectional diameter in the above range and a long columnar shape in the longitudinal direction so that the average cross-sectional diameter is smaller than the inner diameter of the needle capable of being injected into the skin, and the long- If the average cross-sectional diameter of the material for tissue repair is less than 0.08 mm, the strength of the tissue repairing material itself can not be maintained, and therefore, the disintegration period of the body is guaranteed for one year or more And when the average cross-sectional diameter exceeds 0.5 mm, scarring and skin irritation caused by the needle at the time of injecting into the skin are increased, which is undesirable.

The length of the tissue repairing material is not particularly limited because various needles can be used to exhibit optimized efficacy according to a body part into which a tissue repairing material is injected. However, it is preferable not to exceed the maximum length of the needle.

In addition, the content of monomer remaining in polylactic acid, which is the material of the tissue repair material, and the moisture content can also be considered as factors related to the decomposition in the body of the tissue repairing material. The remaining monomer and water content are maintained at a constant level during the manufacturing process, and the residual monomer content is within 2 wt% and the water content is within 0.3 wt% .

According to another aspect of the present invention, there is provided a tissue-

(a) an injection needle, and (b) the above-described tissue-restoring material inserted in the through-hole of the injection needle.

2, the tissue recovery device according to the embodiment of the present invention is inserted into a through-hole of the injection needle 2 according to an embodiment of the present invention.

The length of the injection needle can be adjusted in consideration of the length of the material to be loaded and the site to be implanted, for example, the length of the injection needle exposed to the outside is preferably 10 to 300 mm, 200 mm, more preferably 50 to 150 mm.

3, the apparatus for tissue recovery according to an embodiment of the present invention may further include a fixture 14 for fixing the tissue repairing material 11 to the outer surface of the injection needle 12 have.

The fixture can be used to fix tissue repairing materials to the outer surface of the needles and can be used without limitation as long as it is easy to handle, and can be selected from the group consisting of, for example, sponge or cotton.

The tissue restoration method using the above tissue-recovery device is as follows.

First, the tissue repair material of the present invention is inserted into the through-hole of the injection needle, a part of the tissue repair material is exposed to the outside, and the injection needle is inserted so that the tissue repair material can be positioned under the skin or under the skin .

At this time, the area where the injection needle is inserted into the skin part and the like and the length of the tissue repairing material can be adjusted according to the size of the treatment area. In addition, when the treatment site is wide, the material for tissue repair to be inserted may be sufficiently long to be treated at one time, or several tissue repairing materials may be inserted separately for several times.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Example 1

L-lactic acid having a number average molecular weight of 189,000 obtained by polymerization of L-lactide at 230 占 폚 using a Stenus octoate catalyst was dried under reduced pressure at 100 占 폚 for 6 hours and then fed to a twin-screw kneading extruder having a cylinder temperature of 200 占 폚 And melted and kneaded to homogenize, followed by formation of a chipped composition. Using this composition, a material for tissue regeneration was prepared in the shape of a cylinder having a diameter of 0.2 mm and a length of 5 mm and made of poly-L-lactic acid having a number average molecular weight of 121,000 by an injection molding machine having a barrel temperature of 200 캜 and a mold temperature of 20 캜 .

Example 2

L-lactic acid having a number-average molecular weight of 110,372 was used to obtain a cylindrical-shaped tissue-supporting material made of poly-L-lactic acid having a number average molecular weight of 53,900 was obtained in the same manner as in Example 1, ≪ / RTI >

Example 3

L-lactic acid with a number-average molecular weight of 82,300 was used to obtain a cylindrical tissue-restoring material composed of poly-L-lactic acid having a number-average molecular weight of 32,800, ≪ / RTI >

Example 4

L-lactic acid having a number average molecular weight of 110,372 was used to obtain a cylindrical tissue-restoring material made of poly-L-lactic acid having a number average molecular weight of 53,200 and having a diameter of 0.08 mm and a length of 5 mm A tissue-repairing material was prepared in the same manner as in Example 1.

Example 5

L-lactic acid with a number-average molecular weight of 110,372 was used to obtain a cylindrical tissue-restoring material composed of poly-L-lactic acid having a number average molecular weight of 54,600 and a diameter of 0.5 mm and a length of 5 mm A tissue-repairing material was prepared in the same manner as in Example 1.

Comparative Example 1

L-lactic acid having a number-average molecular weight of 18,600 was obtained by using poly-L-lactic acid having a number average molecular weight of 40,100, a structure was obtained in the same manner as in Example 1, except that a cylindrical- ≪ / RTI >

Assessment of in-vivo degradation characteristics

The materials for tissue repair prepared in Examples 1 to 5 and Comparative Example 1 were inserted into the subcutaneous tissues of the rats using a 23G injection needle and collected in tissues at intervals of 1, 3, 6, and 12 months, The molecular weight was measured and observed with naked eyes.

The number average molecular weight (Mn) of the polylactic acid was measured by GPC. The number average molecular weight of the polylactic acid was 300 or less, indicating that the polylactic acid was decomposed to a monomer or oligomer level, When the molecular weight value was lowered to 300 or less, it was confirmed that the morphology could not be discriminated.

The result of evaluating the decomposition characteristics of the body is shown in FIG.

Referring to FIG. 4, all of the materials for the average number of tissues of Examples 1 to 5 having a number average molecular weight of 30,000 or more were completely decomposed in the body at a number-average molecular weight of 300 or more even after 1 year from injection into the body It was found that it remained.

Specifically, in the case of Example 3 having a number average molecular weight of 32,800, the molecular weight at the end of one year was 900, and polylactic acid decomposed to a large extent was visually confirmed. However, . In addition, in the case of materials for tissue repair using polylactic acid having a larger number average molecular weight as in Examples 1, 2, 4, and 5, a considerable number of tissues are present in a state not decomposed at the end of one year after injection .

On the other hand, in the case of Comparative Example 1 using 18,600 poly-L-lactic acid having a number average molecular weight of 30,000 or less, the number average molecular weight value dropped to 300 or less (about 180) after about six months And it was found that it was decomposed by the naked eye. At the end of one year, there was no substance to be taken into the body, and thus the molecular weight could not be measured.

From this, it was confirmed that the number average molecular weight of the polylactic acid as a material thereof is a very important factor for providing a long-lasting tissue recovery material. In the case of a number average molecular weight of 30,000 or more, And was able to demonstrate the function of tissue regeneration. In addition, it was confirmed that the above-described tissue-repairing substance has an advantage over the long-term effect of the hyaluronic acid formulations, which can last for only 6 months.

1, 11: Materials for tissue repair
2, 12: needles
14:

Claims (1)

Characterized in that it comprises a molten solid of polylactic acid and has a columnar shape extending in the longitudinal direction and having an average cross sectional diameter of 0.08 to 0.5 mm,
Wherein the polylactic acid is a crystalline poly-L-lactic acid, the molten solid of the polylactic acid has a number average molecular weight of 30,000 or more,
Wherein the molten solidification product of polylactic acid is formed by heating polylactic acid at 180 DEG C or higher and melting it, and then molding the polylactic acid into a mold or extruding through a die.

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