KR102230164B1 - A Composition for Coating Suture Comprising Hyaluronic Acid and a Method for Producing Hyaluronic Acid Coated Suture Using the Same - Google Patents

Abstract

The present invention relates to a composition for suture coating comprising hyaluronic acid and a binder, and a method of manufacturing a suture coated with hyaluronic acid using the same, and more particularly, to a suture coating comprising hyaluronic acid and a binder Dissolving a solvent composition, hyaluronic acid, and a binder in purified water to prepare a hyaluronic acid solution; And a method of manufacturing a hyaluronic acid-coated suture comprising the step of coating and then drying the suture with the hyaluronic acid solution, a hyaluronic acid-coated suture prepared by the above manufacturing method, and the hyaluronic acid-coated suture. It relates to a thread for lifting. The suture coating composition according to the present invention and a method of manufacturing a suture coated with hyaluronic acid using the same can be used to produce a suture coated with a high content of hyaluronic acid with high efficiency. The suture coated with a high content of hyaluronic acid of the present invention not only has excellent stability and biocompatibility, but also promotes collagen synthesis, so it can be used as a preparation for various types of tissue repair, and is useful in cosmetic related fields such as lifting threads. Can be used.

Description

A Composition for Coating Suture Comprising Hyaluronic Acid and a Method for Producing Hyaluronic Acid Coated Suture Using the Same}

The present invention relates to a composition for suture coating comprising hyaluronic acid and a binder, and a method of manufacturing a suture coated with hyaluronic acid using the same, and more particularly, to a suture coating comprising hyaluronic acid and a binder Dissolving a solvent composition, hyaluronic acid, and a binder in purified water to prepare a hyaluronic acid solution; And a method of manufacturing a hyaluronic acid-coated suture comprising the step of coating and then drying the suture with the hyaluronic acid solution, a hyaluronic acid-coated suture prepared by the above manufacturing method, and the hyaluronic acid-coated suture. It relates to a thread for lifting.

Suture (縫合絲) means a thread to sew parts of the body damaged by surgery or trauma. In general, sutures are divided into synthetic sutures and natural sutures depending on the raw material, and the absorbent sutures that are naturally degraded and disappear after a certain period of time after being sutured to the wound site depending on whether or not they are absorbed in the body are sutured. It can be classified as a non-absorbable suture that does not decompose afterwards, so that the suture must be removed through reoperation.

Absorbable suture is a degradable polymer material such as cat gut, PGA (polyglycolide), PGLA (polyglycolide-co-lactide), PDO (polydioxanone, polydioxanone), etc., and is mainly used for internal surgery, and non-absorbable suture is silk. As a non-degradable polymer material such as nylon, polypropylene, etc., it is mainly used for surgical operation. Recently, the use of degradable sutures that do not need to be removed after surgery has been increasing. Jangsa, a collagen material, has a short strength retention period due to its high initial swelling and has a slight tissue reaction, but aliphatic polyester-based synthetic polymers such as PGA and PDO are widely used because their strength is maintained longer and less tissue reaction. Among them, the PGA-based suture is used in the form of a multifilament of several strands, and the softer PDO is used in the form of a monofilament.

In recent years, the use of absorbent sutures as a material for tissue repair such as tissue bonding, not as a material for tissue repair, but as a cosmetic-related, and as a lifting thread for wrinkle improvement, has been greatly increased. Lifting thread is a thread that is inserted under the skin to lift aged skin and keep it taut.In particular, wrinkles, which are signs of skin aging, are hidden, skin sagging is prevented, and fibrosis in the dermis proceeds to increase the elasticity of the skin. There is an effect.

Currently, PDO, PLA (polylactide), PCL (polycaprolactone), and PLCL (polylactide-co-caprolactone), which degrade more slowly than PGA, PGLA, and PGCL (polyglycolide-co-caprolactone), which have a short decomposition period, are currently preferred. Among them, PLA and PCL are too slow to decompose, PLA has too hard physical properties, and PCL has too soft properties. On the other hand, PDO is most often used because its strength and flexibility are adequate and its mass decomposition period is as long as 6 months. Lifting threads are inserted under the skin to conceal wrinkles and show elasticity, but more fundamentally, a physiological function of activating fibroblasts and increasing collagen synthesis to enhance the subcutaneous tissue is hoped for. Currently, several studies are being conducted to implement such a tissue-promoting material, and a method of using various proteins and polysaccharides suitable for the human body and excellent in cell affinity is also being studied.

Hyaluronic acid (HA) is a type of glycosaminoglycan (GAG) as an extracellular matrix through which cells can attach and grow.It is widely present in the skin, muscles, cartilage, and blood vessels in the human body. It is a biopolymer material. Hyaluronic acid is an important component that regulates the proliferation and activation of various cells in the human body, and is particularly known as a key element related to anti-aging that accelerates aging by decreasing in the body with aging. Recently, the effect as a skin moisturizing, regeneration, and dermal filler to hide wrinkles has been confirmed, and is widely used in cosmetics, food, and pharmaceutical products. Therefore, by adding hyaluronic acid to the lifting thread, the effect of activating fibroblasts at the inserted site can be expected to promote the production of collagen tissue.

The method of adding hyaluronic acid to the suture can be considered a method of first adding hyaluronic acid to the suture material and melt spinning, but it is almost impossible because hyaluronic acid is not heated and melted. Therefore, it is applied by coating hyaluronic acid on the suture surface. Natural hyaluronic acid has no suitable solvent other than water, and its molecular weight is 1 million to 3 million Da, so its solubility in water is less than 3%. In addition, PDO, PLA, and PCL, which are materials for lifting threads, have strong hydrophobic properties, so that the hydrophilic hyaluronic acid aqueous solution cannot be coated smoothly and evenly on the thread surface, and the amount of coating is less than 104 μg/m per thread length (based on suture USP 2-0). There are only shortcomings.

On the other hand, Korean Patent No. 1784863 proposes a method of manufacturing a suture coated with hyaluronic acid salt, which relates to a method of dissolving a low molecular weight hyaluronic acid salt in a mixed solvent of water and ethanol to coat. However, as described above, the technology using low molecular weight hyaluronic acid has the inconvenience of having to separately modify it to a low molecular weight, and low molecular weight hyaluronic acid may have its physiological function deteriorated, and in particular, there is a disadvantage that it is decomposed earlier in the body. have. In addition, there is a limitation in that the water-ethanol solvent system cannot coat more than 66 μg/m per thread length (based on suture USP 2-0).

In addition, Japanese Laid-Open Patent No. 2011-31034 discloses a coated suture containing a blend of a polymer derived from hyaluronic acid and a vinyl lactam polymer and a polymer derived from a lactone polymer. As for the composition, it is completely different from the purpose of this patent.

Accordingly, as a result of the present inventors making diligent efforts to solve the above problem, a hyaluronic acid solution by dissolving a binder such as PVP (Polyvinylpyrrolidone) or polyacrylic acid together with unmodified high molecular weight natural hyaluronic acid in purified water In the case of manufacturing and coating the suture with the hyaluronic acid solution, it was confirmed that the amount of hyaluronic acid coating was increased and thus a suture having excellent collagen synthesis and moisturizing effect could be prepared, and the present invention was completed.

The information described in the background section is only for improving an understanding of the background of the present invention, and thus does not include information forming the prior art known to those of ordinary skill in the art to which the present invention pertains. May not.

An object of the present invention is to provide a composition for coating sutures comprising hyaluronic acid and a binder.

Another object of the present invention is to provide a method of manufacturing a suture coated with hyaluronic acid using the composition.

Another object of the present invention is to provide a lifting thread comprising a hyaluronic acid-coated suture manufactured by the above manufacturing method and the hyaluronic acid-coated suture.

In order to achieve the above object, the present invention provides a composition for coating sutures comprising hyaluronic acid and a binder.

The present invention also includes the steps of: (a) dissolving hyaluronic acid and a binder in purified water to prepare a hyaluronic acid solution; And (b) coating the suture with the hyaluronic acid solution and then drying the suture.

The present invention also provides a suture in which hyaluronic acid prepared by the above manufacturing method is coated in an amount of 60 μg/m to 6000 μg/m per thread length, and a lifting thread including the hyaluronic acid-coated suture.

The suture coating composition according to the present invention and a method of manufacturing a suture coated with hyaluronic acid using the same can be used to produce a suture coated with a high content of hyaluronic acid with high efficiency. The suture coated with a high content of hyaluronic acid of the present invention not only has excellent stability and biocompatibility, but also promotes collagen synthesis, so it can be used as a preparation for various types of tissue repair, and is useful in cosmetic related fields such as lifting threads. Can be used.

1 to 5 are cross-sectional observation results of a suture coated with hyaluronic acid.
6 is a graph showing the cytotoxicity of the suture coated with hyaluronic acid.
7 is a graph showing the effect of increasing collagen synthesis of a suture coated with hyaluronic acid.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by an expert skilled in the art to which the present invention belongs. In general, the nomenclature used in this specification is well known and commonly used in the art.

Hyaluronic acid is one of the important extracellular matrix in the body and provides an environment in which cells grow, so it has high cell affinity. A method of adding or coating hyaluronic acid is being studied in order to give a function to promote tissue formation in the area by adding a lifting thread to the skin to hide wrinkles and give elasticity, but hyaluronic acid is heated. Since it does not melt, it is almost impossible to add it to the degradable polymer raw material and spun it with suture. Therefore, studies to use hyaluronic acid coated on the surface of the manufactured suture are being conducted. However, natural hyaluronic acid is hydrophilic, but its molecular weight is very high, ranging from 1 million to 3 million Da, so it is not soluble in organic solvents other than water, and it is very difficult to dissolve more than 3% in water. In addition, PDO, PLA, and PCL, which are materials for lifting, have strong hydrophobic properties, so the hydrophilic hyaluronic acid aqueous solution cannot be coated smoothly and evenly on the thread surface, and the coating amount is only 104μg/m or less per thread length (based on suture USP 2-0). There is this.

If hyaluronic acid is denatured with a low molecular weight, the solubility in water or organic solvents may increase, but it is also only soluble in a solvent in which water and a small amount of alcohol are mixed, and it is difficult to coat a large amount evenly on the surface of the hydrophobic suture. There is a disadvantage of only 66 μg/m or less per length of transfer thread (based on suture USP 2-0). In addition, hyaluronic acid modified with a low molecular weight has a disadvantage of shortening the residence period in the body due to poor cell affinity and rapid decomposition.

However, according to the present invention, when the suture is coated by adding a binder in a specific concentration range to the natural aqueous hyaluronic acid solution, the amount of hyaluronic acid to be coated can be increased, and at the same time, the hyaluronic acid is evenly and lubricated. In addition, since hyaluronic acid is not modified to a low molecular weight, the original cell affinity is not reduced and the residence time in the body is not shortened. The coated natural hyaluronic acid increased collagen synthesis by enhancing the cell affinity of the inserted lifting thread, thus reducing wrinkles and increasing the elasticity of the skin.

Therefore, in one aspect, the present invention relates to a composition for coating sutures comprising hyaluronic acid and a binder.

In the present invention, the term “binder” refers to an additive material that has a property that adheres well to substrates to be coated, so that a coating material can be coated well and a lot of coating can be applied.

In the present invention, the binder is PVP (polyvinylpyrrolidone, polyvinylpyrrolidone), which is a water-soluble polymer that is safe for the human body, polyacrylic acid (PAA), polyacryl amide (PAAm), polyhydroxyethyl methacrylate (PHEMA), It may be characterized in that it is selected from the group consisting of polyvinyl alcohol (PVA) and copolymers thereof, but is not limited thereto.

In the present invention, the molecular weight of the hyaluronic acid may be characterized in that 1 million to 3 million Da, it may be characterized in that the natural state hyaluronic acid, but is not limited thereto.

In the existing hyaluronic acid coating method, when the suture is coated by immersion or spray spraying because the aqueous solution exhibits viscosity due to high molecular weight, there is a problem in that it is difficult to dissolve in an organic solvent aqueous solution as well as difficulty in adjusting the coating thickness. , The hyaluronic acid coating method using a binder according to the present invention does not use an organic solvent, and has a feature of coating natural high molecular weight hyaluronic acid with a uniform thickness.

In the present invention, the hyaluronic acid may be in the form of hyaluronic acid, and the hyaluronic acid is a salt in which a salt is bound to hyaluronic acid, and sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, etc. may be exemplified, but limited thereto. It does not become.

In the present invention, the concentration of hyaluronic acid may be 0.5 to 2.5% (w/v), and the concentration of the binder may be 0.1 to 3% (w/v), but is not limited thereto. Preferably, the concentration of hyaluronic acid is 0.7 to 1.5% (w/v), and the concentration of the binder is 0.2 to 1.4% (w/v).

In one embodiment of the present invention, when the concentration of hyaluronic acid is 0.5% (w/v) or less, the amount of hyaluronic acid coating on the suture is small, and thus there is no effect, and when the concentration of hyaluronic acid is 1.5% (w/v) or more, hyaluronic acid is added to purified water. There was a problem that it did not melt well. In addition, PVP was used as a binder in an embodiment of the present invention, and if there is no PVP, it is difficult to coat hyaluronic acid on the suture, and when it is 1% (w/v) or more, there is a problem that the coating amount of PVP is increased than that of hyaluronic acid.

In the present invention, the suture is PGA (polyglycolide), PGLA (polyglycolide-co-lactide), PGCL (polyglycolide-co-caprolactone) PLA (polylactide), PDO (polydioxanone), PCL (polycaprolactone), and PLCL (polylactide-co). -caprolactone) It may be characterized in that it is selected from the group consisting of sutures, but is not limited thereto.

In another aspect of the present invention, (a) preparing a hyaluronic acid solution by dissolving hyaluronic acid and a binder in purified water; And (b) coating the suture with the hyaluronic acid solution and then drying the suture.

In the present invention, the binder is selected from the group consisting of polyvinylpyrrolidone (PVP), polyacrylic acid (PAA), polyacryl amide (PAAm), polyhydroxyethyl methacrylate (PHEMA), polyvinyl alcohol (PVA), and copolymers thereof. It can be, but is not limited thereto.

In the present invention, the molecular weight of the hyaluronic acid may be characterized in that 1 million to 3 million Da, it may be characterized in that the natural state hyaluronic acid, but is not limited thereto.

In the present invention, the concentration of hyaluronic acid may be 0.5 to 2.5% (w/v), and the concentration of the binder may be 0.1 to 3% (w/v), but is not limited thereto. Preferably, the concentration of hyaluronic acid is 0.7 to 1.5% (w/v), and the concentration of the binder is 0.2 to 1.4% (w/v).

In the present invention, the suture is PGA (polyglycolide), PGLA (polyglycolide-co-lactide), PGCL (polyglycolide-co-caprolactone) PLA (polylactide), PDO (polydioxanone), PCL (polycaprolactone), and PLCL (polylactide-co). -caprolactone) It may be characterized in that it is selected from the group consisting of sutures, but is not limited thereto.

In the present invention, the hyaluronic acid solution in steps (a) and (b) may be stored at 0 to 40°C, but is not limited thereto.

In an embodiment of the present invention, it was confirmed that when the storage temperature of the hyaluronic acid solution was 0° C. or less, the purified water was frozen and coating was difficult, and when the hyaluronic acid solution was 40° C. or more, decomposition of hyaluronic acid occurred.

In the present invention, the coating speed in step (b) may be characterized in that 1 to 5 cm/min, and the drying temperature in step (b) may be characterized in that it is 40 to 100°C, but limited thereto. It does not become.

In one embodiment of the present invention, when the coating speed is 1 cm/min or less, the productivity is lowered, and when the coating speed is 5 cm/min or more, the hyaluronic acid coating liquid is not well dried, so that the amount of hyaluronic acid coating decreases. When the drying temperature is 40°C or less, it takes a long time to dry, and when the drying temperature is 100°C or more, hyaluronic acid is decomposed.

In the present invention, the suture of step (b) may be characterized in that hyaluronic acid is coated in an amount of 60 μg/m to 6000 μg/m per thread length. Preferably, it may be characterized in that the content is 80 μg/m to 5000 μg/m per thread length, but is not limited thereto.

Unlike prior arts that could not manufacture sutures having a hyaluronic acid content of 60 μg/m or more, in the present invention, a suture having a high content of hyaluronic acid was prepared. In one embodiment of the present invention, the amount of hyaluronic acid coating of the prepared suture was 60 μg/m to 5000 μg/m.

In another aspect, the present invention relates to a suture in which hyaluronic acid prepared by the above method is coated in an amount of 60 μg/m to 6000 μg/m per thread length.

In another aspect, the present invention relates to a lifting thread including the hyaluronic acid-coated suture.

Modern people have a special interest in the beauty of the face or body part exposed to the outside, and accordingly, thread lifting procedures have recently been increasing. This thread lifting procedure is an intermediate procedure between laser and surgery, and is gaining great popularity because it can obtain an effect comparable to that of surgery without much burden on daily life.

The thread lifting procedure is a method of lifting the skin in a desired direction after inserting the lifting thread into the subcutaneous layer of sagging and sagging skin. In the area where the lifting thread is inserted, wrinkles are hidden, skin sagging is prevented, and fibrosis in the dermis proceeds, thereby increasing elasticity of the skin.

Hereinafter, the present invention will be described in more detail through examples. These examples are for illustrative purposes only, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not construed as being limited by these examples.

Example 1: hyaluronic acid and PVP ( Poly Vinyl Pyrrolidone ) Preparation of hyaluronic acid solution containing

Molecular weight of 1.5 million Da hyaluronic acid (BLOOMAGE FREDA BIOPHARM CO., LTD, Sodium Hyaluronate, HA-EP-N 2.5 / molecular weight: 1.3 million-1.5 million Da) was dissolved in purified water, and PVP (Ashland, POVIDONE K) as a binder -90, / molecular weight: 1.3 million g/mol) was dissolved. It was dissolved by stirring for 2 hours at room temperature (RT).

The prepared hyaluronic acid solution was stored at 0 to 40°C, and after 24 hours after preparation, hyaluronic acid was decomposed and denatured by the microbial hyaluronidase, so it was used for suture coating within 24 hours.

Example 2: Preparation of hyaluronic acid-coated suture

PDO (polydioxanone) suture (METABIOMED CO., LTD, MEPFIL-D, suture size: USP 2-0 (diameter: 0.353 ~ 0.378mm or USP 3&4 (diameter: 0.636 ~ 0.661mm)) in the hyaluronic acid solution prepared in Example 1 )) was dipped at a rate of 1 to 5 cm/min, followed by drying at a facility setting temperature (40° C.) and a hot air blower (6 to 80° C.) by a heat drying method to prepare a hyaluronic acid-coated suture.

Example 3: Hyaluronic acid of hyaluronic acid-coated suture Coating amount Confirm

Example 3-1: hyaluronic acid coated PDO Suture Amount of hyaluronic acid Experimental method for quantification

The hyaluronic acid-coated PDO suture was extracted in distilled water at 37° C. for 30 minutes, and 5 ml of disodium tetraborate (dissolved in JUNSEI, sodium tetraborate anhydrous) in Reagent A (sulfuric acid (JUNSEI, sulfuric acid)) was added and reacted for 15 minutes. After adding 0.2 ml of Reagent B (dissolving carbazole (DAEJUNG, Carbazole) in ethanol (SAMCHON, Ethyl alcohol, anhydrous 99.9%)) and reacting for 15 minutes, use a UV/VIS Spectrometer (PerkinELMER, UV/VIS Spectrometer, Lambda 25). Absorbance was measured at 530 nm by using (EUROPEAN PHARMACOPOEIA 8.0, 01/2005:1472). ^{NH of carbazole, an indicator, and COO-} of Glucoronic acid of hyaluronic acid (Glucoronic acid + N-Acetyl glusocamine), are combined to develop a red color. The chemical reaction formula is shown in the following formula (1).

[Formula 1]

Example 3-2: PVP ( polyvinyl pyrrolidone ) Binder and hyaluronic acid coated suture ( USP 2- Of 0) Hyaluronic acid Coating amount Confirm

When PVP is used as a binder, the quantitative results of hyaluronic acid coating of the suture (suture size: USP 2-0) are shown in Table 1 below.

Sample Absorbance μg/m D.W 0.0025 - PDO USP 2-0 0.0072 - 2% PVP + 1% HA 0.094 60 1% PVP + 1% HA 0.236 333 0.5% PVP + 1% HA 0.2675 394

The coating rate of 2% PVP + 1% HA was 60 μg/m, the coating rate of 1% PVP + 1% HA was 333 μg/m, and the coating rate of 0.5% PVP + 1% HA was 394 μg/m.

Example 3-3: PVP ( polyvinyl pirrolidone ) Binder and hyaluronic acid coated suture ( USP 3& 4) of Hyaluronic acid Coating amount Confirm

When PVP is used as a binder, the quantitative results of hyaluronic acid coating of the suture (suture size: USP 3 & 4) are shown in Table 2 below.

Sample Absorbance
(2 Bae Hee-Seok) μg/m D.W 0.0025 - PDO USP 3&4 0.0072 - 2% PVP + 1% HA 0.944 3387 1% PVP + 1% HA 1.211 4418 0.5% PVP + 1% HA 1.347 4941

The coating rate of 2% PVP + 1% HA was 3387 μg/m, the coating rate of 1% PVP + 1% HA was 4418 μg/m, and the coating rate of 0.5% PVP + 1% HA was 4941 μg/m.

Example 3-4: When a binder is not used, a hyaluronic acid-coated suture ( USP 2- Of 0) Hyaluronic acid Coating amount Confirm

When the binder is not included, the quantitative results of the hyaluronic acid coating of the suture (suture size: USP 2-0) are shown in Table 3 below. The 1% HA coating rate was 105 μg/m.

Sample Absorbance μg/m D.W 0.0005 - PDO USP 2-0 0.0001 - 1% HA 0.1171 105

Example 3-5: When a binder is not used, a hyaluronic acid-coated suture ( USP Hyaluronic acid of 3&4) Coating amount Confirm

When the binder is not included, the quantitative results of the hyaluronic acid coating of the suture (suture size: USP 3 & 4) are shown in Table 4 below. The 1% HA coating rate was 530 μg/m.

Sample Absorbance μg/m D.W 0.0023 - PDO USP 3&4 0.0081 - 1% HA 0.338 530

Example 3-6: PVA ( polyvinyl alcohol ) Binder and hyaluronic acid coated suture (USP 2- Of 0) Hyaluronic acid Coating amount Confirm

When PVA (SIGMA-ALDRICH, Polyvinyl alcohol / molecular weight: 30,000-70,000g/mol) is used as a binder, the quantitative results of hyaluronic acid coating of the suture are shown in Table 5 below.

Sample Absorbance μg/m D.W 0.0011 - PDO USP 2-0 0.0064 - 2% PVA + 1% HA 0.1562 180 1% PVA + 1% HA 0.1275 125 0.5% PVA + 1% HA 0.1926 250

The coating rate of 2% PVA + 1% HA was 180 μg/m, the coating rate of 1% PVA + 1% HA was 125 μg/m, and the coating rate of 0.5% PVA + 1% HA was 250 μg/m.

Example 3-7: PAA ( polyacrylic acid ) Binder and hyaluronic acid coated suture ( USP 2- Of 0) Confirmation of hyaluronic acid coating amount

When PAA (SIGMA-ALDRICH, Polyacrylic acid / molecular weight: 1.25 million g/mol) is used as a binder, the quantitative results of hyaluronic acid coating of the suture are shown in Table 6 below.

Sample Absorbance μg/m D.W 0.0154 - PDO USP 2-0 0.0005 - 2% PAA + 1% HA 0.0948 62 1% PAA + 1% HA 0.1061 84 0.5% PAA + 1% HA 0.1378 145

The coating rate of 2% PAA + 1% HA was 62 μg/m, the coating rate of 1% PAA + 1% HA was 84 μg/m, and the coating rate of 0.5% PAA + 1% HA was 145 μg/m.

As a result, it was confirmed that the coating amount was very small when hyaluronic acid was coated alone, and the hyaluronic acid coating amount increased when a hydrophilic binder (PVP, PVA, PAA, etc.) was used. In addition, in the case of PVP, even if only 0.5% is used, the same effects as 2% PVP and 1% PVP appear, so it is more efficient.

Example 4: Check the cross section of the suture coated with hyaluronic acid

In order to measure the uniformity and coating thickness of the hyaluronic acid coating, the cross section of the suture coated with hyaluronic acid was examined with an optical microscope (SOME TECH, SV-55, PLUS CAMSCOPE, the cross section of the sample cut to about 1 mm was observed at a magnification of 600 times). Observed.

As a result, as shown in Figs. 1 to 5, there was a difference in the coating amount of hyaluronic acid depending on the concentration of the binder and hyaluronic acid, but the coating thickness of each suture was uniform at about 4 to 5 μm (Table 7).

Average thread diameter (μm) Average coating area (μm) PDO USP 2-0 423 - 1% HA 420 4.7 2% PVP + 1% HA 466 4.6 1% PVP + 1% HA 457 4.2 0.5% PVP + 1% HA 478 5.6

Example 5: Confirmation of cytotoxicity of hyaluronic acid-coated suture

To confirm the safety of the hyaluronic acid-coated suture, the presence or absence of cytotoxicity was examined.

When WST-1 reacts with the mitochondrial hydrogenase of the mitochondrial organelle, it develops orange color, and absorbance was measured at 450 nm using a Microplate reader (Thermo SCIENTIFIC, MULTISKAN FC).

As a result, the cell viability of the PDO suture not coated with hyaluronic acid was 98.7%, and the cell viability of the suture containing 1% HA was 97.0% (FIG. 6). Therefore, the hyaluronic acid-coated PDO suture has no cytotoxicity, so safety can be secured.

Example 6: Confirmation of collagen synthesis effect of hyaluronic acid-coated suture

In order to confirm the effect of hyaluronic acid-coated suture on skin regeneration and elasticity maintenance, the expression of collagen synthesis gene was observed.

Mouse fibroblast L929 cells were cultured by injecting suture extract coated with hyaluronic acid, and RNA was extracted to synthesize cDNA. A qPCR (quantitative polymerase chain reaction) experiment was conducted to measure the expression level of COL1A1, a collagen synthesis gene (FIG. 7).

As shown in FIG. 7, the expression of COL1A1 was increased in the comparative medium containing 2.5 to 10 μg of HA than that of the general culture medium (control) without HA. The expression of was increased by 1.416 times. This means that the hyaluronic acid-coated suture extract increases the expression level of the collagen synthesis gene, and that hyaluronic acid may have an effect on the increase of collagen synthesis.

Example 7: Small molecule Hyaluronic acid coated suture and Coating amount compare

Table 8 shows the quantitative results of low molecular weight hyaluronic acid (BLOOMAGE FREDA BIOPHARM CO., LTD, Sodium Hyaluronate, HA-EP1) having a molecular weight of 290,000 Da. The low molecular weight 1% HA coating rate was 69 μg/m, and the low molecular weight 1% HA + 70% ethanol coating rate was 66 μg/m.

Sample Absorbance μg/m D.W 0.0011 - PDO USP 2-0 0.0001 - Low molecular weight 1% HA 0.0983 69 Small Molecular 1% HA + 70% Ethanol 0.0971 66

As described above, specific parts of the present invention have been described in detail, and it will be apparent to those of ordinary skill in the art that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereby. will be. Accordingly, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (14)

A composition for suture coating comprising hyaluronic acid and a binder, wherein the binder is polyvinylpyrrolidone (PVP), polyacrylic acid (PAA), polyacryl amide (PAAm), polyhydroxyethyl methacrylate (PHEMA), polyvinyl alcohol (PVA). ) And suture coating composition, characterized in that selected from the group consisting of these copolymers.
delete The composition of claim 1, wherein the hyaluronic acid has a molecular weight of 1 million to 3 million Da.
The composition of claim 1, wherein the concentration of hyaluronic acid is 0.5 to 2.5% (w/v), and the concentration of the binder is 0.1 to 3% (w/v).
The method of claim 1, wherein the suture is PGA (polyglycolide), PGLA (polyglycolide-co-lactide), PGCL (polyglycolide-co-caprolactone) PLA (polylactide), PDO (polydioxanone), PCL (polycaprolactone), and PLCL (polylactide- Co-caprolactone) suture coating composition, characterized in that selected from the group consisting of sutures.
A method of manufacturing a hyaluronic acid-coated suture comprising the following:
(a) preparing a hyaluronic acid solution by dissolving hyaluronic acid and a binder in purified water; And
(b) drying the suture after coating the suture with the hyaluronic acid solution;
Here, the binder is selected from the group consisting of polyvinylpyrrolidone (PVP), polyacrylic acid (PAA), polyacryl amide (PAAm), polyhydroxyethyl methacrylate (PHEMA), polyvinyl alcohol (PVA), and copolymers thereof.
delete The method of claim 6, wherein the hyaluronic acid in the step (a) has a molecular weight of 1 million to 3 million Da.
The hyaluronic acid according to claim 6, wherein the concentration of hyaluronic acid in step (a) is 0.5 to 2.5% (w/v), and the concentration of the binder is 0.1 to 3% (w/v). A method of manufacturing a coated suture.
The method of claim 6, wherein the coating speed in step (b) is 1 to 5 cm/min.
The method of claim 6, wherein the drying temperature in step (b) is 40 to 100°C.
The method of claim 6, wherein the suture of step (b) is coated with hyaluronic acid in an amount of 60 μg/m to 6000 μg/m per thread length.
A suture in which hyaluronic acid prepared by the method according to claim 6 is coated in an amount of 60 μg/m to 6000 μg/m per thread length.
A lifting thread comprising a suture coated with hyaluronic acid of claim 13.

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