KR20230119461A - Composition for tissue repair treatment and method for preparing the same - Google Patents

Abstract

The present invention relates to a tissue repair composition and a method for preparing the same, and more particularly, to a tissue repair composition based on the total weight of polyglutamate crosslinked material 1 to 10% by weight, hyaluronic acid 0.5 to 10% by weight and the remainder of the solvent Including, the weight ratio of the polyglutamate crosslinked product and hyaluronic acid is from 1: 1 to 1: 4 relates to a composition for tissue repair.

Description

Composition for tissue repair and method for preparing the same {COMPOSITION FOR TISSUE REPAIR TREATMENT AND METHOD FOR PREPARING THE SAME}

The present invention relates to a composition for tissue repair and a method for preparing the same, and more particularly, to a composition having excellent moisture absorption and moisturizing power, easy control of physical properties, and improved biocompatibility through mixing of cross-linked poly-gamma-glutamic acid and non-cross-linked hyaluronic acid. It relates to a composition for tissue repair and a method for preparing the same.

As the structure of society changes and the population increases, the number of patients with burns, bedsores, trauma, cosmetic surgery, intractable ulcers, and diabetic skin necrosis gradually increases, and treatment methods for damaged skin are also developing accordingly. Tissue repair materials are materials used for replacement, restoration, and reconstruction of human tissues such as blood vessels, heart, diaphragm, fascia, and skin (dermal, cutaneous), and are industrially classified as medical devices. The concept of materials for tissue repair is quite broad, and fillers, which are injections used for cosmetic procedures such as facial and skin wrinkle improvement, as well as materials for medical purposes that replace damaged biological tissues, are included in the category of materials for tissue repair.

Currently, hyaluronic acid fillers, which are most widely used as fillers, have a very low half-life in the body of 1 to 3 days, and have a problem in that reabsorption occurs very quickly in vivo. In order to use water-soluble hyaluronic acid as a filler, it is necessary to form a crosslinked product with appropriate viscoelasticity. However, 1,4-butanediol diglycidyl ether (BDDE), which is used to induce a chemical crosslinking reaction of hyaluronic acid, has toxicity such as carcinogenicity. Therefore, after formation of the crosslinked material, chemicals such as BDDE should be removed by dialysis to a level below the residual tolerance level. Since the dialysis process period is required to meet the corresponding standard, there is a high possibility of loss such as process cost increase and product disposal due to biochemical contamination. Accordingly, as in Korean Patent Publication No. 10-2004-0072008, a product in which hyaluronic acid and a crosslinking material are crosslinked to each other to extend the resorption period is being sold. However, problems due to the toxicity of cross-linked materials have been reported even in such cross-linked products.

The most important quality factor of the filler is the control of the physical properties that determine the viscosity, elasticity and injection force of the filler. The physical properties of the hyaluronic acid filler are mainly determined by the crosslinking reaction conditions such as the concentration of the crosslinking agent including BDDE, and the pulverization method of the crosslinked product. Currently commercially available hyaluronic acid fillers are largely divided into monophasic products mainly composed of crosslinked materials in a gel state and biphasic products in which a crosslinked material in gel and particle form is mixed. The monophasic product controls the physical properties of the product by the cross-linking level of the crosslinked product, and the biphasic product controls the physical properties by the particle size. The physical properties of the filler are represented by viscosity and elasticity. If the viscosity is high, the filler is soft and has high spreadability and adhesiveness, and if the elasticity is high, the shape is maintained for a long time after skin injection. In general, the viscosity and elasticity of a filler are in inverse proportion. That is, when the viscosity is increased, the elasticity is lowered, and when the elasticity is increased, the viscosity is lowered. High-viscosity-low-elasticity fillers are mainly used to remove fine wrinkles on thin skin, such as around the eyes or lips, and low-viscosity-high-elasticity fillers are used in areas where maintaining volume is important, such as the bridge of the nose, forehead, and deep wrinkles.

Hyaluronic acid filler manufacturers are constructing product lineups with different physical properties depending on the treatment site or purpose of treatment through manufacturing technology that can adjust viscosity and elasticity for each manufacturer. However, in order to produce products with different physical properties, crosslinking reaction conditions and grinding methods of crosslinked products must be different for each product, so constant quality control is difficult and process costs increase.

Therefore, it is necessary to develop a technology that can more easily control products with various physical properties suitable for biomaterials for tissue repair without concern for toxicity caused by chemical crosslinking processes and the like without chemical crosslinking reactions.

Accordingly, one aspect of the present invention is to provide a tissue repair composition having excellent moisture absorption and moisturizing power, easy control of physical properties, and improved biocompatibility through mixing of crosslinked poly-gammaglutamic acid and non-crosslinked hyaluronic acid.

According to one aspect of the present invention, the composition for tissue repair comprises 1 to 10% by weight of polyglutamate crosslinked material, 0.5 to 10% by weight of hyaluronic acid and the remainder of the solvent based on the total weight of the tissue repair composition, and the polyglutamate crosslinked material and The weight ratio of hyaluronic acid is 1:1 to 1:4, and a composition for tissue repair is provided.

According to the present invention, it is possible to obtain a composition for tissue repair, which does not require chemical crosslinking, is excellent in safety, and can secure various physical properties and functionality suitable for a biomaterial for tissue repair.

Figure 1 shows a photograph of the composition for tissue repair each prepared by Examples and Comparative Examples.
Figure 2 is a graph showing the results of measuring the hyaluronic acid decomposition inhibitory effect of the composition for tissue repair each prepared by Examples and Comparative Examples.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. However, the embodiments of the present invention may be modified in various forms, and the scope of the present invention is not limited to the embodiments described below.

According to the present invention, it is possible to obtain a composition for tissue repair and a manufacturing method thereof, which are materials that are excellent in safety because no chemical crosslinking is required and secure functionality, physical properties, and safety suitable for biomaterials for tissue repair.

In the present invention, "for tissue repair" includes cosmetic fillers, cosmetic implants, and the like, but is not limited thereto and means that the use is not particularly limited as long as it can be used as a biomaterial.

On the other hand, in the present invention, "tissue repair composition" means a composition containing a polyglutamate crosslinked product and hyaluronic acid as raw materials used in the manufacture of tissue repair materials, "tissue repair material" means tissue It means any material including a composition for repair or may be used interchangeably with a composition for tissue repair.

More specifically, according to the present invention, the composition for tissue repair comprises 1 to 10% by weight of polyglutamate crosslinked material, 0.5 to 10% by weight of hyaluronic acid and the remainder of the solvent based on the total weight of the tissue repair composition, and the polyglutamate crosslinked material And the weight ratio of hyaluronic acid is 1: 1 to 1: 4, a composition for tissue repair is provided. When the content of hyaluronic acid exceeds the above weight ratio, the tanδ value according to the following formula 1 is less than 0.4, and the elastic property is excessively large, so it may be unsuitable for use as a biomaterial for tissue repair.

tanδ = G" (loss modulus)/ G' (storage modulus)...[Equation 1]

At this time, the tanδ means a value obtained by dividing G" (loss modulus) by G' (storage modulus), and the ratio of G"/G' is called the loss ratio (tanδ), and δ means the phase value of strain and stress. . Therefore, a large loss ratio is viscous and a small loss ratio is elastic.

In the present invention, the crosslinked polyglutamate crosslinked product is a tissue repair composition in which polyglutamate having a molecular weight (Mw) of more than 500 kDa and less than 3000 kDa is dissolved in 0.5 to 25% by weight in water, saline, or a combination thereof. to 60 kGy electron beams were irradiated.

The tissue repair composition of the present invention contains 1 to 10% by weight, preferably 1.5 to 5% by weight of poly-gamma-glutamate crosslinked crosslinked by electron beam, and 0.5 to 10% by weight of hyaluronic acid. , Preferably in an amount of 1 to 5% by weight, the balance may be a composition for tissue repair dissolved in a solvent. At this time, when the content of the poly-gamma-glutamate crosslinked product is less than 1% by weight, the concentration is too low to secure the physical properties as a filler, and when it exceeds 10% by weight, a hard crosslinked product with very high G' and G" is formed. On the other hand, when the concentration of hyaluronic acid is less than 0.5% by weight, the effect on physical properties is low, and when the concentration exceeds 10% by weight, the hyaluronic acid solution has a high viscosity. There is a problem that is difficult to manufacture.

At this time, it is preferable to use gamma (γ) polyglutamic acid as the polyglutamic acid of the present invention. On the other hand, hyaluronic acid may be prepared and applied in an aqueous solution, and at this time, the content of the final solvent may be prepared to fall within the scope of the present invention.

The solvent that can be used in the present invention is preferably at least one selected from the group consisting of water and saline, but is not particularly limited thereto, and other solvents that ensure biocompatibility and safety may be used.

Meanwhile, the polyglutamic acid salt is preferably in the form of at least one salt selected from the group consisting of sodium, potassium, calcium, ammonium and zinc salts, and for example, polyglutamic acid sodium salt may be used.

The composition for tissue repair of the present invention can be prepared as a material for tissue repair by homogeneous mixing, wherein the G 'modulus (storage modulus) is the storage modulus and represents elasticity, and the G "modulus (loss modulus) is Viscosity is expressed as a loss modulus, and all units of Pa or dyne/cm ² are used.

The tissue repair composition of the present invention has a storage modulus (G ') of 10 to 1500 Pa and a loss modulus (G ") of a tissue repair composition of 0.4 to 50 Pa, for example, the tissue repair composition of the present invention. Silver has a storage modulus (G') of 5 to 1000 Pa, or 20 to 1000 Pa, for example 100 to 500 Pa, and a loss modulus (G") of 0.5 to 40 Pa. When the storage modulus (G') is less than 10 Pa, G' is very low, so there is no resistance to deformation, so there is a problem of insufficient physical properties to be used as a biomaterial for tissue repair, and when it exceeds 1500 Pa, G' is On the other hand, there is a problem that is not suitable for use as a biomaterial for tissue repair because it becomes stiff due to a lack of G ".

In addition, the tissue repair composition has a tanδ value of 0.4 to 5 according to Formula 1, more preferably 0.5 to 2.

The material for tissue repair of the present invention may be used for cosmetic fillers, cosmetic implants, or a combination thereof, but is not limited thereto, and is not particularly limited as long as it can be applied as a biomaterial.

According to the present invention, it is possible to obtain a composition for tissue repair that has excellent stability because no chemical crosslinking is required, does not require a separate sterilization process, and has functionality, physical properties, and safety suitable for a biomaterial for tissue repair.

On the other hand, according to another aspect of the present invention, a method for preparing the tissue repair composition of the present invention is provided.

The polyglutamate crosslinked product of the present invention may be prepared by irradiating radiation, and the radiation is preferably selected from the group consisting of gamma rays, electron beams, and X-rays. can The irradiating of the radiation is performed at a dose of 1 to 500 kGy, preferably at a dose of 3 to 100 kGy, and more preferably at a dose of 4 to 30 kGy.

When the dose is less than 1 kGy, there is a problem of not forming a cross-linked product due to insufficient cross-linking in polyglutamic acid due to an insufficient amount of free radical generation, and when the dose exceeds 500 kGy, excessive cross-linking is formed, resulting in G' and G" Since this very high rigid cross-linked body is formed, there is a problem in that the physical properties are inappropriate for use as a material for tissue repair. At this time, the G ' modulus (storage modulus) is the storage modulus, which represents elasticity, and the G " modulus (loss modulus) is Viscosity is expressed as a loss modulus, and all units of Pa or dyne/cm ² are used.

More specifically, polyglutamate may be obtained by radiation irradiation at a dose of 1 to 500 kGy to a composition for tissue repair in which 0.5 to 25% by weight is dissolved in a solvent.

When the polyglutamate crosslinked product is obtained by this process, the composition of the present invention can be prepared by mixing it with hyaluronic acid and a solvent in the content ratio of the present invention. At this time, the order and method of mixing the polyglutamate crosslinked product, hyaluronic acid, and the solvent are not particularly limited. For example, at least one of the polyglutamate crosslinked product and hyaluronic acid is first mixed in a solvent, or the polyglutamate crosslinked product and hyaluronic acid may be mixed with the solvent in one step, and may be mixed homogeneously with, for example, stirring.

The composition may be further subjected to a step of standing at room temperature for 1 minute to 24 hours, if necessary. At this time, room temperature may mean a range of 4 to 40 ° C.

Hereinafter, the present invention will be described in more detail through specific examples. The following examples are merely examples to aid understanding of the present invention, and the scope of the present invention is not limited thereto.

Example

1. Preparation of composition for tissue repair

Poly-gamma-glutamic acid sodium salt (Bioleaders) powder having a molecular weight of 2,000 kDa was taken in a beaker, phosphate buffered saline (PBS) was added thereto to a concentration of 4% by weight, and the mixture was dissolved by stirring for about 1 hour at 200 rpm in a stirrer.

As a result, the obtained aqueous solution was irradiated with an absorbed dose of 20 kGy electron beam to obtain a poly-gamma-glutamic acid crosslinked product. At this time, the electron beam irradiation was performed in a 10 Mev LINAC-electron accelerator (Model ELV-4, 1 Mev, Korea Atomic Energy Research Institute, Jeong-Eup, Korea). At this time, the intensity of the beam current was 1 mA, and the energy of the electron beam was 10 Mev. After electron beam irradiation, the total absorbed dose was checked with an alanine dosimeter (Ceric cerous dosimeter, Bruker Instruments, Germany), and the error of the total absorbed dose was within 5%.

Hyaluronic acid sodium salt (BLOOMAGE BIOTECHNOLOGY CORP., LTD) having a dry molecular weight of 1,500 to 2,000 kDa was taken in a beaker, PBS was added thereto to a concentration of 4% by weight, and the result was dissolved by stirring in a stirrer at 200 rpm for about 4 hours.

The cross-linked poly-gamma-glutamic acid and the aqueous solution of sodium salt of hyaluronic acid were mixed homogeneously at 20,000 rpm for 3 times for 10 minutes each in a mixer with a knife while adding PBS. At this time, the final weight % ratio of the poly-gamma-glutamic acid electron beam crosslinked product and hyaluronic acid in each case applied is as shown in Table 1 below, based on the total weight of the composition.

Polygammaglutamic acid (% by weight) Hyaluronic acid (% by weight) weight ratio Comparative Example 1 2.0 0.0 - Example 1 2.0 0.5 4:1 Comparative Example 2 1.5 0.0 - Example 2 1.5 0.5 3:1 Comparative Example 3 1.0 0.0 - Example 3 1.0 0.5 2:1 Example 4 1.0 1.0 1:1

Photos of some of the materials obtained as a result are shown in FIG. 1 . When 0.5 ml of the material prepared according to each Example and Comparative Example was placed on a flat plate and left at room temperature, the material with a high content of electron beam cross-linked poly-gamma-glutamic acid maintained its initial shape, but the content of electron beam-crosslinked poly-gamma-glutamic acid As it lowered, it showed a pattern of spreading laterally over time.

2. Confirmation of the physical properties of the composition for tissue repair

Rheological properties are one of the important factors representing the physical properties of crosslinked hydrogels. The physical properties of each sample obtained in the above Examples and Comparative Examples were measured using a rheometer (MCR-92, Anton Paar Ltd.). A dynamic time sweep test was conducted in the range of 0.01 to 1 Hz using 25 ° C and 25 mm Plate Geometry, and G' (storage modulus, storage modulus), G” (loss modulus, Loss modulus) and tanδ (loss ratio) were confirmed, and the results are shown in Table 2.

At this time, the tanδ was calculated by Equation 1 below.

tanδ = G" (loss modulus)/ G' (storage modulus)...[Equation 1]

G'(Pa)
storage modulus G” (Pa)
loss modulus tanδ
loss ratio Comparative Example 1 574.01 134.33 0.234 Example 1 549.18 281.01 0.512 Comparative Example 2 211.68 47.87 0.226 Example 2 224.95 159.14 0.707 Comparative Example 3 2.75 1.31 0.476 Example 3 20.50 32.49 1.582 Example 4 62.12 79.39 1.278

As can be seen in Table 2 above, as the content of the poly-gamma-glutamic acid crosslinked product increases, the G' value of the crosslinked product increases. In an example containing the same content of poly-gamma-glutamic acid crosslinked product, the G' value and G" value change according to the change in the content of hyaluronic acid, and the pattern of change tends to be different depending on the content of poly-gamma-glutamic acid crosslinked product. That is, when the content of the poly-gamma-glutamic acid crosslinked product is 1.5% by weight or more, when hyaluronic acid is added, the G' value does not change significantly, but the G" value increases. On the other hand, when the content of the poly-gamma-glutamic acid crosslinked product is 1.0% by weight or less, both the G' value and the G" value increase when hyaluronic acid is added. This is because water-soluble hyaluronic acid is incorporated between the poly-gamma-glutamic acid cross-linked material particles during the process of homogeneous mixing of the poly-gamma-glutamic acid cross-linked material and hyaluronic acid, and the physical properties change in proportion to the concentration of hyaluronic acid.

Therefore, according to the present invention, by adjusting the content of the poly-gamma-glutamic acid cross-linked product and the content of hyaluronic acid, it is possible to control G' and G”, and tanδ of the poly-gamma-glutamic acid cross-linked product, and, if necessary, a biomaterial requiring low viscoelasticity to biomaterials requiring high viscoelasticity.

3. Injection power of biomaterials for tissue repair

In order to find out the ease of injection when injecting each sample prepared in the above Examples and Comparative Examples, the injection force was comparatively measured with an extrusion force meter (Multi test 2.5-dV, Mecmesin). After inserting the prefilled syringe containing the sample of Example or Comparative Example to be measured into the jig, the injection force was measured at a rate of 12 mm/min by adjusting the syringe pusher to be located in the center of the fixing plate.

Injection force (N) Comparative Example 1 24.95 Example 1 8.73 Comparative Example 2 6.86 Example 2 4.71 Comparative Example 3 3.81 Example 3 3.28 Example 4 3.13

As can be seen in Table 3, the injection power of the crosslinked product increases as the content of the poly-gammaglutamic acid crosslinked product increases. On the other hand, in the example containing the same amount of poly-gamma-glutamic acid crosslinked product, the higher the content of hyaluronic acid, the lower the injection power. In particular, the injection force of Comparative Example 1 prepared with only 2.0% by weight of the poly-gamma-glutamic acid crosslinked product was 24.95 N, but the injection force of Example 1 prepared by adding 0.5% by weight of hyaluronic acid was rapidly lowered to 8.73. This indicates that when an appropriate amount of hyaluronic acid is added to the highly elastic poly-gamma-glutamic acid crosslinked product, the injection force is lowered while maintaining the elasticity, thereby making the procedure easier.

4. Moisturizing power of biomaterials for tissue repair

The moisturizing power of each material prepared in the Examples and Comparative Examples was measured, and the results are shown in Table 4. At this time, the measurement of the moisturizing power was measured by weighing 10 g of the sample prepared in Example or Comparative Example, putting it in a Petri dish, and leaving it in a dryer at 40 ° C., measuring the weight at intervals of 6 hours to calculate the relative weight ratio.

relative weight (%) 0 hours 6 hours 12 hours 18 hours 24 hours Comparative Example 1 100.0 88.5 51.3 32.4 19.5 Example 1 100.0 91.2 60.2 37.6 25.2 Comparative Example 2 100.0 83.8 42.7 28.2 15.1 Example 2 100.0 85.5 44.1 32.2 18.9 Comparative Example 3 100.0 68.9 34.5 19.7 6.4 Example 3 100.0 71.1 36.5 22.1 7.9 Example 4 100.0 76.0 39.3 22.9 9.3

As can be seen in Table 4, as the content of the poly-gamma-glutamic acid crosslinked product increases, the moisturizing power of the crosslinked product increases. On the other hand, in the example containing the same amount of poly-gamma-glutamic acid crosslinked product, the higher the content of hyaluronic acid, the higher the moisturizing power. That is, when an appropriate amount of hyaluronic acid is added to the poly-gamma-glutamic acid crosslinked product, a material with higher moisturizing power can be produced.

5. Inhibition of hyaluronic acid decomposition of biomaterials for tissue repair

Non-crosslinked hyaluronic acid is easily degraded by hyaluronic acid degrading enzymes present in living organisms. Therefore, there is a problem in that it is difficult to expect efficacy such as tissue repair by injecting uncrosslinked hyaluronic acid into the human body. However, when the hyaluronic acid degrading enzyme is treated with the composition prepared in the present invention, the decomposition of uncrosslinked hyaluronic acid can be inhibited, which inhibits the activity of the polygammaglutamic acid crosslinked hyaluronic acid degrading enzyme. is due to In order to confirm this, among the materials prepared in Examples and Comparative Examples, the degree of decomposition of hyaluronic acid of the mixture of poly-gamma-glutamic acid crosslinked material and hyaluronic acid was measured, and the results are shown in FIG. 2 .

At this time, the hyaluronic acid decomposition test method is as follows.

1) Enzyme reaction

Example 1 and a control sample containing only 0.5% by weight of hyaluronic acid based on the total composition were each weighed 1 g each into a 50 ml tube. Hyaluronic acid degrading enzyme was prepared by dissolving hyaluronidase in a phosphate buffer solution (pH 7.0, 10 mM PBS, NaCl 0.8%, hereinafter referred to as 'PBS') to be 30 units/ml. After adding 6 ml of hyaluronidase solution to each tube containing 1 g of each sample, the mixture was reacted at 37° C. for 24 hours to decompose hyaluronic acid. 18 ml of distilled water was added to each sample and vigorous stirring was performed for 10 seconds to stop the reaction. After centrifugation at 4,000 rpm for 15 minutes, 1 ml of the supernatant was taken and centrifuged at 12,000 rpm for 5 minutes. Take the supernatant into a 10 ml glass vial.

2) Quantification (carbazole assay)

The taken supernatant was reacted with carbazole to determine the glucuronic acid content.

About 0.1 g of D-glucuronic acid is precisely measured and mixed with 100 ml of a saturated benzoic acid solution. 3 ml of this mixed solution is taken and mixed with 97 ml of physiological saline, and this is used as a standard solution of glucuronolactone.

After the hyaluronic acid decomposition reaction, 800 ul of physiological saline was added to 200 ul of the supernatant of the centrifuged solution to make exactly 1 ml, and this was used as the sample solution. In the last glass vial, only water was added to make a blank test solution. Add 5 ml of borax sulfate TS to each glass vial and shake vigorously to mix. After leaving it in a boiling water bath for 10 minutes, it was immediately cooled in ice water. 0.2 ml of 0.125 w/v% carbazole ethanol solution was added to each glass vial, capped, shaken vigorously, left in a water bath for 15 minutes, and cooled to room temperature with ice water. With these solutions, the absorbance was measured at a wavelength of 530 nm using a blank test solution as a control according to the UV-visible absorbance measurement method. Using a calibration curve prepared from the average absorbance of the standard solution (the following formula corresponds to this), the amount and decomposition rate of ttrium hyaluronate in the sample solution were obtained, and the results are shown in FIG. 2 .

* Degradation rate (%)

= Amount of decomposed sodium hyaluronate (mg) / Mass of lyophilized sample (mg) × 100

* Amount of sodium hyaluronate (%)

= Amount of decomposed sodium hyaluronate (mg) × 25

(Here, 25 means the volume of 25 ml of the test solution.)

* Amount of decomposed sodium hyaluronate (mg)

= Amount of glucuronolactone standard (mg) × (Ar-A0/As-A0) × dilution factor × 2.28

(Here, the dilution factor is calculated by the following formula,

Dilution factor=concentration of standard solution/concentration of test solution=(3/10,000)/[volume of test solution/(volume of test solution+0.8))],

At this time, 2.28 is a calculated value of the molecular weight of 1 unit of sodium hyaluronate (401.30)/molecular weight of glucuronolactone (176.17).

_Ar is the absorbance of the test solution, _{As is} the absorbance of the standard solution, and A ₀ is the absorbance of the control solution.)

* Mass of lyophilized sample = HA content of sample (mg/mL) × mass of sample

As a result, as shown in FIG. 2, about 82% of the control sample (Free HA) containing only hyaluronic acid was degraded after 48 hours of hyaluronic acid degrading enzyme reaction, but the poly-gammaglutamic acid crosslinked product contained 0.5% by weight of hyaluronic acid. It was confirmed that only about 33% of the sample (HA + PGA) of Example 1 was degraded after 48 hours of hyaluronic acid degrading enzyme reaction. This indicates that the poly-gamma-glutamic acid crosslinking agent inhibits the activity of hyaluronic acid degrading enzyme.

Therefore, it can be expected that when the composition prepared according to the present invention is injected subcutaneously, the decomposition of uncrosslinked hyaluronic acid is delayed, so that effects such as moisturizing and wrinkle improvement and maintenance period can be improved.

Although the embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and variations are possible without departing from the technical spirit of the present invention described in the claims. It will be obvious to those skilled in the art.

Claims (7)

Based on the total weight of the tissue repair composition, 1 to 10% by weight of the polyglutamate crosslinked product, 0.5 to 10% by weight of hyaluronic acid, and the balance of the solvent, the weight ratio of the polyglutamate crosslinked product to hyaluronic acid is 1:1 to 1:4, tissue repair composition.
According to claim 1, wherein the cross-linked polyglutamate crosslinked body molecular weight (Mw) of more than 500 kDa to less than 3000 kDa polyglutamate in water, saline or a combination thereof is dissolved in 0.5 to 25% by weight tissue repair composition To which the electron beam of 4 to 60kGy is irradiated, tissue repair composition.
According to claim 1, wherein the solvent, water, and at least one selected from the group consisting of saline, tissue repair composition.
According to claim 1, wherein the polyglutamate is sodium, potassium, calcium, at least one salt form selected from the group consisting of ammonium and zinc, tissue repair composition.
According to claim 1, wherein the tissue repair composition has a storage modulus (G ') of 10 to 1500 Pa,
A composition for tissue repair.
According to claim 1, wherein the composition for tissue repair is a tanδ value of 0.4 to 5 according to Formula 1, tissue repair composition.
tanδ = G" (loss modulus)/ G' (storage modulus)...[Equation 1]
According to claim 1, wherein the material for tissue repair, used for the purpose of cosmetic fillers, cosmetic implants, or a combination thereof, tissue repair composition.