Biomaterial composition for tissue repair comprising a mixture of DNA fragments and a polyhydric alcohol

Abstract

The present invention relates to a tissue repair composition comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol; a filler composition; a tissue repair method using the same; and tissue repair applications.

Description

[Technical Field]

[0001] The present invention relates to a tissue repair composition comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol; a filler composition; a tissue repair method using the same; and tissue repair applications. [Background technology]

[0002] As interest in anti-aging grows, there has been an increase in procedures aimed at improving deficiencies in the body, such as joints, cardiovascular system, and skin. For example, cosmetic procedures aimed at improving wrinkles and other cosmetic conditions fall into this category. In recent years, there has been a rise in the use of biocompatible materials to replace damaged tissue and increase volume in desired body parts.

[0003] For example, there are filler compositions that use hyaluronic acid as the main ingredient, but some hyaluronic acid fillers have high viscosity and low elasticity, making them difficult to inject into the skin, and even after injection, they do not maintain the injected shape for long, resulting in a short shape retention period.To address this issue, various compounds have been added (U.S. Patent No. 11,154,481), but it is still somewhat difficult to address the issues while minimizing side effects. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent No. 11,154,481 [Non-patent literature]

[0005] [Non-Patent Document 1] Park, No-June, et al. “Compound K improves skin barrier function by increasing SPINK5 expression.” Journal of Ginseng Research 44.6 (2020): 799-807 Summary of the Invention [Problem to be solved by the invention]

[0006] There remains a need for the development of improved biomaterials for tissue repair. [Means for solving the problem]

[0007] One object of the present invention is to provide a composition for tissue repair comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol, wherein the DNA fragment mixture is contained in an amount of 2 to 5% by weight of the total composition, and the polyhydric alcohol is contained in an amount of 0.5 to 4% by weight of the total composition.

[0008] Another object of the present invention is to provide a filler composition comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol, wherein the DNA fragment mixture is contained in an amount of 2 to 5 wt % of the total composition, and the polyhydric alcohol is contained in an amount of 0.5 to 4 wt % of the total composition.

[0009] Another object of the present invention is to provide a method for tissue repair, which comprises administering the tissue repair composition or filler composition to an individual.

[0010] Another object of the present invention is to provide a composition for tissue repair, comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol, wherein the DNA fragment mixture is contained in an amount of 2 to 5% by weight of the total composition, and the polyhydric alcohol is contained in an amount of 0.5 to 4% by weight of the total composition. [Effects of the Invention]

[0011] The biomaterial for tissue repair of the present invention has not only tissue repair ability but also a moisturizing effect, and has the excellent effect of not causing a dry feeling in the tissue. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 shows the results of confirming the effect of increasing water content through animal experiments. [Figure 2] FIG. 10 is a diagram showing standardized evaluation results of injection force for manufactured comparative examples and examples. [Figure 3] FIG. 10 is a diagram showing the phase angle evaluation results for the manufactured comparative example and example. [Figure 4] FIG. 10 is a diagram showing the phase angle evaluation results for the manufactured comparative example and example. [Figure 5] FIG. 10 is a diagram showing the phase angle evaluation results for the manufactured comparative example and example. [Figure 6] FIG. 10 is a diagram showing the phase angle evaluation results for the manufactured comparative example and example. [Figure 7] FIG. 10 is a diagram showing the evaluation results of biodegradability for the produced comparative examples and examples. [Figure 8] FIG. 1 is a graph showing the results of comparing the height and width of the injection site after injection of the liquid compositions prepared in Comparative Examples and Examples. [Figure 9] FIG. 1 shows the results of comparing the properties of each liquid composition during production. DETAILED DESCRIPTION OF THE INVENTION

[0013] This will be explained in more detail as follows: Each description and embodiment disclosed in the present invention also applies to each other description and embodiment. In other words, any combination of various elements disclosed in the present invention falls within the scope of the present invention. Furthermore, the following specific description is not considered to limit the category of the present invention. Furthermore, throughout this specification, numerous papers and patent documents are referenced and citations thereof are displayed. The disclosure contents of the cited papers and patent documents are incorporated herein by reference in their entirety to more clearly explain the state of the art to which the present invention pertains and the content of the present invention.

[0014] One aspect of the present invention provides a composition for tissue repair, comprising a DNA fragment mixture and an alcohol, wherein the alcohol may be a polyhydric alcohol, more specifically a C3 or C4 polyhydric alcohol.

[0015] In one embodiment, the tissue repair composition of the present invention is characterized by a composition for tissue repair comprising an active ingredient consisting of a mixture of DNA fragments; and a C3 or C4 polyhydric alcohol. In the present invention, the term "DNA fragment mixture" refers to a mixture of nucleic acid fragments having a certain range of molecular weights, which includes DNA, a biopolymer consisting of phosphate, four bases, and deoxyribose, and which exists as a nucleotide polymer. The DNA fragment mixture may be present in the form of fragments with reduced molecular weights, but is not limited thereto, and may be used interchangeably as "DNA fragments," "DNA fractions," "nucleic acid fragments," and "nucleic acid fragment mixtures."

[0016] In one embodiment, the DNA fragment mixture of the present invention may be a polynucleotide (PN), a polydeoxyribonucleotide (PDRN), or a mixture thereof.

[0017] In the present invention, the term "polynucleotide" is also referred to as "PN" and refers to a DNA or RNA chain, which is a polymer of nucleotides in which nucleotide units are linked in a chain by covalent bonds. In addition, in the present invention, the term "polydeoxyribonucleotide" is also referred to as "PDRN" and may refer to, but is not limited to, a type of low molecular weight DNA complex having a specific molecular weight. For example, the polynucleotide may have a relatively long nucleic acid length or a large molecular weight compared to polydeoxyribonucleotides. It may be used as a raw material for medical devices due to its role as a physical support, providing cell adhesion, lubrication, and buffering effects. Polydeoxyribonucleotides may be used as a raw material for pharmaceuticals for cell proliferation and tissue regeneration, but are not limited to these.

[0018] In one embodiment, the liquid formulation of the DNA fragment mixture of the present invention may contain a buffer solution, which may be at least one selected from the group consisting of sodium phosphate monobasic dihydrate, sodium phosphate dibasic dodecahydrate, sodium chloride, magnesium chloride, potassium chloride, phosphate buffer saline, or HEPES (N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid), but is not limited thereto.

[0019] The DNA fragment mixture according to any of the above-mentioned embodiments may be obtained by extraction from fish testes or semen. Specifically, the fish may be a salmonid fish. More specifically, the fish may be a salmon or a trout, but is not limited thereto.

[0020] The DNA fragment mixture according to any of the above-mentioned embodiments may have a molecular weight of about 1 to 100,000 kDa, 5 to 50,000 kDa, 50 to 10,000 kDa, or 50 to 1,500 kDa.

[0021] In one embodiment according to any of the above-mentioned embodiments, the DNA fragment mixture of the present invention may be, but is not limited to, PN (polynucleotide).

[0022] The DNA fragment mixture according to any of the above-mentioned specific examples may be contained at 2 to 7% by weight relative to the total tissue repair composition, specifically, 2 to 6% by weight, 2 to 5% by weight, 2 to 4% by weight, 2 to 3% by weight, 3 to 7% by weight, 3 to 6% by weight, 3 to 5% by weight, 3 to 4% by weight, 4 to 7% by weight, 4 to 6% by weight, 4 to 5% by weight, 5 to 7% by weight, 5 to 6% by weight, 6 to 7% by weight, or 6 to 7% by weight.

[0023] The C3 or C4 polyhydric alcohol of the present invention refers to an alcohol having 3 or 4 carbon atoms and two or more hydroxyl groups (-OH).

[0024] The polyhydric alcohol according to any of the above-mentioned specific examples may be contained in an amount of 0.5 to 8% by weight relative to the total composition, and more specifically, it may be contained in an amount of 0.5 to 8% by weight, 0.5 to 7% by weight, 0.5 to 6% by weight, 0.5 to 5% by weight, 0.5 to 4% by weight, or 0.5 to 3% by weight. It may be contained at 0.5 to 2% by weight, 0.5 to 1% by weight, 1 or more and less than 8% by weight, 1 to 7% by weight, 1 to 6% by weight, 1 to 5% by weight, 1 to 4% by weight, 1 to 3% by weight, 1 to 2% by weight, 2 or more and less than 8% by weight, 2 to 7% by weight, 2 to 6% by weight, 2 to 5% by weight, 2 to 4% by weight, 2 to 3% by weight, 3 or more and less than 8% by weight, 3 to 7% by weight, 3 to 6% by weight, 3 to 5% by weight, 3 to 4% by weight, 4 or more and less than 8% by weight, 4 to 7% by weight, 4 to 6% by weight, 4 to 5% by weight, 5 or more and less than 8% by weight, 5 to 7% by weight, or 5 to 6% by weight.

[0025] The polyhydric alcohol in any of the above-mentioned specific examples may be any one or more selected from the group consisting of glycerin, propylene glycol, and butylene glycol, but is not limited thereto.

[0026] In the present invention, it was confirmed that polyhydric alcohols alone cannot be used for tissue repair, but that the combination of a DNA fragment mixture and a C3 or C4 polyhydric alcohol can reduce viscosity and increase ease of injection.

[0027] Furthermore, when a DNA fragment mixture is combined with the polyhydric alcohols polyethylene glycol (PEG) and triethylene glycol, a large amount of bubbles are generated during the production of the liquid composition, which increases the probability of defective products during subsequent product production, and the viscosity approaches 0, making it impossible to use for tissue repair. However, it has been confirmed that the possibility of this occurring is significantly lower when the DNA fragment mixture of the present invention is combined with a C3 or C4 polyhydric alcohol.

[0028] On the other hand, the tissue repair composition of the present invention may have tissue moisturizing ability.

[0029] In the present invention, the term "tissue moisturizing ability" means increasing the water content of tissue. The tissue moisturizing ability of the present invention may be an increase in the water content of tissue upon injection of the composition of the present invention compared to when the composition is not injected into the tissue. Such moisturizing ability may be an increase in the water content within the tissue, or may contribute to tissue repair with a high engraftment rate and increased moisture without causing a dry feeling in the surrounding tissue, but rather alleviating the dry feeling.

[0030] In another embodiment, the tissue repair composition may increase the water content of tissue upon injection into the tissue.

[0031] An example of such tissue may include, but is not limited to, skin.

[0032] In one embodiment of the present invention, it was confirmed that a tissue repair composition further containing a C3 or C4 polyhydric alcohol (especially at a specific content) not only has an excellent tissue repair effect when injected into tissue compared to a DNA fragment mixture alone, but also increases the moisture content. This suggests that when the composition of the present invention is injected, it does not excessively absorb moisture from adjacent tissues, but provides moisture to the adjacent tissues, and does not cause a dry feeling in the surrounding tissues, but rather alleviates the dry feeling, resulting in a high engraftment rate and a tissue repair effect with good moisture.

[0033] In particular, in a composition containing a DNA fragment mixture and a C3 or C4 polyhydric alcohol, when the DNA fragment mixture is contained in an amount of 2 to 5 wt% of the total composition and the polyhydric alcohol is contained in an amount of 0.5 to 4 wt% of the total composition, it was confirmed that there is a critical meaning for the moisturizing effect, and that excellent tissue repair effects are achieved within the same range.This suggests that within the above-mentioned content combination range, the dryness feeling is not imparted to the surrounding tissue, but rather the dryness feeling is alleviated, and there is a tissue repair effect with good moisturizing feeling.

[0034] In any of the above-described specific examples of the composition for tissue repair, the DNA fragment mixture and the polyhydric alcohol may be contained in a weight ratio of 10:1 to 1:2, but is not limited thereto.

[0035] In one embodiment of any of the above-mentioned specific examples, in the composition for tissue repair of the present invention, the DNA fragment mixture and the polyhydric alcohol may be contained in a weight ratio of about 10:1 to 1:2, 10:1 to 1:1, 8:1 to 1:2, 8:1 to 1:1, 6:1 to 1:2, 6:1 to 1:1, 5:1 to 1:2, 5:1 to 1:1, 4:1 to 1:2, or 4:1 to 1:1, specifically, about 10:1 to 1:2, 10:1 to 1:1, or 6:1 to 1:2.

[0036] The term "about" includes not only the exact number listed after the term, but also nearly that number or a range close to that number. Whether a number is close to or approximately that specific number can be determined by considering the context in which the number is presented. For example, the term "about" can refer to a range of -10% to +10% of a given number. For another example, the term "about" can refer to a range of -5% to +5% of a given number. For other examples, the range may include, but is not limited to, ±0.5, ±0.4, ±0.3, ±0.2, ±0.1, etc.

[0037] In the present invention, even if the word "about" is omitted before a numerical value, it is obvious that the present invention includes the range in which the word "about" is not omitted.

[0038] Meanwhile, the term "for tissue repair" in the present invention means that it is used to replace, repair, and / or reconstruct human tissues and organs such as blood vessels, heart, diaphragm, fascia, and / or skin.

[0039] The composition for tissue repair of the present invention is used as a biomaterial for tissue repair, and the biomaterial for tissue repair refers to a bio-derived material used for replacing, repairing, or reconstructing human tissues and organs such as blood vessels, heart, diaphragm, fascia, and skin, and is not limited to cosmetic fillers but refers to a biomaterial for tissue repair specified by the Ministry of Food and Drug Safety.

[0040] The tissue repair composition of the present invention may be a liquid composition or an injectable composition, but is not limited thereto.

[0041] In the present invention, the term "injectable" refers to a material having the properties required for administering the composition to an individual using an injection device with a needle.

[0042] In the present invention, the term "administration" refers to introducing the composition of the present invention into an individual by any suitable method, and the administration route can be various routes such as topical application, subcutaneous administration, dermal administration, intravascular administration, biological membrane administration, tissue fiber administration, and synovial administration, as long as the target tissue can be reached. The dosage form may be, but is not limited to, topical administration, subcutaneous injection, dermal injection, intravascular injection, intramuscular injection, joint cavity injection, tendon injection, and ligament injection. The preferred dosage of the composition of the present invention may vary depending on the condition of the individual.

[0043] The tissue repair composition according to the present invention may have a viscosity in an appropriate range that allows it to be injected into the target tissue.

[0044] The term "viscosity" used in this invention means the property of a fluid, i.e., the appearance of a flow with viscosity, which is resistance to flow. Such viscosity can be expressed by viscosity, particularly complex viscosity (η*, Pa s).

[0045] In other specific examples, the tissue repair composition exhibits a complex viscosity of 1 to 2,000 Pa·s, specifically 5 to 2,000 Pa·s, 8 to 2,000 Pa·s, 1 to 1,500 Pa·s, 5 to 1,500 Pa·s, 8 to 1,500 Pa·s, 1 to 1,300 Pa·s, 5 to 1,300 Pa·s, or 8 to 1,300 Pa·s.

[0046] The viscosity range of tissue repair compositions typically used as tissue repair biomaterials is between about 1 Pa·s and about 8,000 Pa·s. Within this viscosity range, tissue repair compositions can naturally settle into tissues in vivo after administration. Generally, tissue repair compositions with a viscosity range of about 1 Pa·s or less can settle into the body, but their ability to self-form is reduced, preventing them from functioning as a tissue repair biomaterial for creating volume. Furthermore, even with a small amount of force, a large amount of injection solution can be injected, making it difficult to control the injection volume. Furthermore, viscosity ranges of about 8,000 Pa·s or more can make it difficult to push the syringe out during injection into the body, making it difficult to inject an accurate amount due to the application of excessive force during injection, and can result in side effects due to the difficulty in precisely controlling the injection volume.

[0047] The tissue repair composition of the present invention can be injected with an injection force of 0 or more when administered at a rate of 50 mm / min, and an extrusion force of about 60 N, about 55 N, about 50 N, about 45 N, about 40 N, about 35 N, about 30 N, or about 25 N or less. By way of example, the injection force may be that obtained by injection through a 33-gauge needle, but is not limited thereto. Specifically, in accordance with the moldable filler approval review guideline standards, it is appropriate for the injection force to be set at 40 N or less.

[0048] The tissue repair composition of the present invention may further comprise one or more compounds selected from the group consisting of anesthetics, vitamins, amino acids, metals, antioxidants, and mineral salts, but is not limited thereto.

[0049] The tissue repair composition of the present invention may further contain any suitable excipient commonly used in the art, and such excipients may be, for example, but are not limited to, preservatives, wetting agents, dispersing agents, suspending agents, buffers, stabilizers, or isotonicity agents.

[0050] Another aspect of the present invention provides a biomaterial for tissue repair comprising the tissue repair composition of the present invention.

[0051] The tissue repair composition and tissue repair biomaterial are as described in other aspects.

[0052] Another aspect of the present invention provides a filler composition comprising a DNA fragment mixture and an alcohol, wherein the alcohol may be a polyhydric alcohol, more specifically a C3 or C4 polyhydric alcohol.

[0053] The DNA fragment mixture may be contained in an amount of 2 to 5% by weight relative to the total composition, and the polyhydric alcohol may be contained in an amount of 0.5 to 4% by weight relative to the total composition.

[0054] In the present invention, the term "filler" refers to a medical device that is injected into the skin as a tissue repair material for volume restoration, etc., and has the principle of action of maintaining the volume of the skin through physical repair.

[0055] The DNA fragment mixture, polyhydric alcohol, etc. are as described in other embodiments, and the filler composition may be one specific example of a tissue repair composition. All of the above-mentioned details regarding the tissue repair composition of the present invention (DNA fragment mixture, polyhydric alcohol, their contents, weight ratios, tissue moisturizing ability, liquid composition, injectable composition, administration, viscosity in an appropriate range for injection, etc.) can also be applied to the filler composition.

[0056] The filler composition of the present invention may further comprise one or more compounds selected from the group consisting of, but not limited to, anesthetics, vitamins, amino acids, metals, antioxidants, and mineral salts.

[0057] The filler composition of the present invention may further comprise any suitable excipient commonly used in the art, such as, but not limited to, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer, or an isotonicity agent.

[0058] Another aspect of the present invention is to provide a method of tissue repair comprising administering to an individual a tissue repair or filler composition of the present invention.

[0059] The administration, tissue repair, tissue repair composition, filler composition, etc. are as described in other aspects.

[0060] In the present invention, the term "individual" refers to any animal, including humans, such as mice, rats, livestock, etc., that is in need or may be in need of tissue repair. Specifically, it may be a mammal, including humans.

[0061] Another object of the present invention is to provide a use of a composition comprising a DNA fragment mixture and a C3 or C4 polyhydric alcohol for tissue repair, wherein the DNA fragment mixture is contained in an amount of 2 to 5% by weight of the total composition, and the polyhydric alcohol is contained in an amount of 0.5 to 4% by weight of the total composition.

[0062] The DNA fragment mixture, polyhydric alcohol, tissue repair, etc. are as described in other embodiments. [Example]

[0063] The present invention will be described in more detail below through experimental examples. However, the following examples are merely preferred embodiments for illustrating the present invention, and are not intended to limit the scope of the present invention. Meanwhile, technical matters not described in this specification can be fully understood and easily performed by those skilled in the technical field of the present invention or a similar technical field.

[0064] Manufacturing example: Manufacturing of biomaterials for tissue repair containing a mixture of DNA fragments and polyhydric alcohols The DNA fragment mixture was added to a buffer solution and dissolved at a high temperature of 60-80°C using a thermostirrer to prepare a DNA fragment mixture solution. After adding and mixing a polyhydric alcohol to the DNA fragment mixture solution prepared using a thermostirrer at 60-80°C, the temperature of the mixed solution was lowered to room temperature to prepare a liquid formulation.

[0065] At that time, PN (polynucleotide; manufacturer: Pharma Research) was used as a representative example of a DNA fragment mixture, and the sample names and concentrations were prepared as shown in Tables 1 and 2 below.

[0066] [Table 1]

[0067] [Table 2] JPEG2026500984000004.jpg134170

[0068] Experimental example 1: Confirmation of moisturizing effect through animal experiments A skin water loss model was created using mice as a representative example of tissue, following a previously published method (Park, No-June, et al. "Compound K improves skin barrier function by increasing SPINK5 expression." Journal of Ginseng Research 44.6 (2020):799-807).

[0069] The liquid composition prepared in Preparation Example was injected into the living body of the prepared animal model, and the moisture content of the mouse skin was measured under conditions of 25±5°C and 50%±5% RH using a moisture measuring device (Corneometer® CM 825 (Courage + Khazaka electronic GmbH, Germany)).

[0070] As a result, as shown in FIG. 1, it was confirmed that in the case of the examples containing a specific DNA fragment mixture ratio and glycerin content and ratio, a higher water content (moisturizing effect) was imparted to the tissue.

[0071] In particular, it was confirmed that a composition containing 2-5 wt% of the DNA fragment mixture and 0.5-4 wt% of the polyhydric alcohol in the total composition is critical for moisturizing effect. As described below, it was confirmed that the same content range provides excellent tissue repair effects in terms of viscosity, injection force, injection feel, and biodegradability. This suggests that the aforementioned content combination range provides a tissue repair effect with a higher engraftment rate and a more moisturizing feel.

[0072] Experimental Example 2: Viscosity Evaluation The complex viscosity (η*, Pa·s; hereinafter, viscosity) of the liquid compositions prepared in Comparative Examples 1 to 6 and Examples 8 to 33, which involved the DNA fragment mixture alone, glycerin alone, and a combination of the DNA fragment mixture and glycerin, was measured 48 hours after preparation using a rheometer (NETZSCH (Germany), Kinexus Ultra+ Rheometer). Specifically, the viscosity was measured under the following conditions: measurement temperature: 25°C, geometry used: PU20, gap: 1.0 mm, measurement frequency: 0.1 Hz, shear strain: 0.5%, analysis program: rSpace for Kinexus. The results are shown in Table 3 below.

[0073] [Table 3] JPEG2026500984000006.jpg179170

[0074] As a result, as shown in Table 3, it was confirmed that glycerin alone (Comparative Example 6) had a viscosity similar to that of purified water and therefore could not be used for tissue repair, while the combinations of DNA fragment mixtures and glycerin (Examples 8 to 33) showed a decreased viscosity compared to the DNA fragment mixtures alone (Comparative Examples 1 to 5). This suggests that the combinations of DNA fragment mixtures and glycerin (Examples 8 to 33) may be more easily injected.

[0075] Experimental Example 3: Evaluation of injection force The injection force was measured for Comparative Examples 1 to 5 and Examples 8 to 33, except for glycerin alone (Comparative Example 6), which was confirmed in Experimental Example 2 to be unsuitable for tissue repair.

[0076] The injection force indicates the force (N) required to inject the injection solution, and was measured at an injection rate of 50 mm / min. All liquid compositions prepared in Examples and Comparative Examples for which the injection force was confirmed were measured using an injection force measuring device (tensile and compression tester) 48 hours after preparation. Specifically, the injection force was measured using a tensile and compression tester (Universal Testing Machine (UTM), Dahua Testing Machine (Republic of Korea)) under the following conditions: measurement temperature: 25±2°C, injection needle: JBP Korea (Republic of Korea), 33G nano needle, injection rate: 50 mm / min. The results are shown in Table 4 below and Figure 2.

[0077] [Table 4] JPEG2026500984000008.jpg125170

[0078] The injection force values ​​of the glycerin-free compositions (Comparative Examples 1 to 5) were replaced with 100%, and the values ​​of the Examples based on the DNA fragment mixture of the same content were normalized with the values ​​of the Comparative Examples. The results are shown in percentage in Figure 2.

[0079] As a result, as shown in Table 4 and Figure 2, it was confirmed that the injection force was weakened when combined with glycerin compared to the DNA fragment mixture alone, and that even though the injection force of the comparative example was high, the injection force adjustment effect of the example in which the DNA fragment mixture and glycerin were combined was great.

[0080] Experimental Example 4: Evaluation of injection sensation With the exception of glycerin alone (Comparative Example 6), which was confirmed to be unusable for tissue repair in Experimental Example 2, the injection feel of the representative comparative examples and examples was evaluated, taking into consideration that the injection force must be set to 40 N or less according to the moldable filler approval examination guidelines, excluding Examples 32 and 33, which did not meet this requirement.

[0081] A blind test was conducted among independently recruited experimenters (4 people). The experimenters evaluated the injection feel by using a syringe needle (33 gauge nano needle) used in the actual product to inject the compositions of each comparative example and experimental example into a petri dish. The relevant conditions were all the same as those for the injection force test, except that no equipment was used. The easier the injection, the higher the score, and the more difficult the injection, the higher the score. The results are shown in Tables 5 and 6 below. Table 5 shows the number of people who received each score.

[0082] [Table 5]

[0083] [Table 6]

[0084] As shown in Tables 5 and 6, the evaluation score for the actual pouring sensation was lower when the DNA fragment mixture was combined with glycerin (Example 8, etc.) than when it was used alone (Comparative Examples 1, 2, and 4), demonstrating that the pouring sensation was superior.

[0085] Experimental Example 5: Evaluation of Phase Angle The phase angle (δ, °) of the liquid compositions prepared in each Example and Comparative Example was measured 48 hours after preparation using a rheometer (NETZSCH (Germany), Kinexus Ultra+ Rheometer). Specifically, the phase angle was measured under the following conditions: measurement temperature: 25°C, geometry used: PU20, gap: 1.0 mm, measured Hz: 0.1 Hz, shear strain: 0.5%, analysis program: rSpace for Kinexus. The results are shown in Figures 3 to 6.

[0086] As a result, as shown in Figures 3 to 6, when the DNA fragment mixture was combined with glycerin (Examples 8 to 31) compared to the DNA fragment mixture alone (Comparative Examples 1 to 4), the phase angle increased, further increasing fluidity, suggesting that injection ease may be improved.

[0087] Experimental Example 6: Comparison of biodegradability of biorepair materials with and without DNA fragment mixtures and polyhydric alcohols Liquid compositions containing DNA fragment mixtures and / or polyhydric alcohols (glycerin, propylene glycol, butylene glycol) in the ranges described in Comparative Example 6 and Example 28 were injected into mice. The mice were SKH-1 hairless mice, 6 weeks old, female, and housed in a temperature of 22±2°C and a relative humidity of 50±10%, with food and water available ad libitum. The test period consisted of one week of acclimation before the samples were injected, and the mice were sacrificed 60 hours later. 100 μL of the sample was injected intradermally into the back of the mice, and measurements were taken. After sample injection, the volume change at the injection site was observed, and the results were confirmed using 3D photo simulation (Primos, Canfield, USA), and are shown in Figure 7.

[0088] As a result, as shown in Figure 7, when polyhydric alcohols (glycerin, propylene glycol, butylene glycol) were used alone, they were completely decomposed immediately after injection, confirming that they could not be used for tissue repair purposes. However, when the DNA fragment mixture was combined with polyhydric alcohols (glycerin, propylene glycol, butylene glycol), they were still present after 60 hours, confirming their suitability as biorepair materials.

[0089] Experimental Example 7: Comparison of height and width after injection of liquid composition If the tissue repair biomaterial spreads too much after being injected into the body, the repair effect may be minimal. If the area is narrow but the height is high, it may be too noticeable to the naked eye and aesthetically, which may cause problems such as protrusions or hives. Therefore, the area and height after injection were evaluated.

[0090] The mice used in this study were SKH-1 hairless mice, 6 weeks old, female. They were kept in a temperature of 22±2°C and a relative humidity of 50±10%, with food and water available ad libitum. After a one-week acclimation period, the samples were injected, and measurements were taken immediately after injection. The mice were then sacrificed seven days later. 100 μL was injected intradermally on the back of the mice, and measurements were taken. To this end, the liquid compositions of the Comparative Examples and Examples prepared in the above Preparation Examples were injected into the body of a mouse, and the height and width of the injected sample were measured using a vernier caliper (MITUTOYO (Japan)) and analyzed using Image software. The results are shown in Figure 8 and Table 7.

[0091] [Table 7]

[0092] As shown in Table 7 and FIG. 8, when compared with a commercial product (Rejuran; RJR; Pharma Research Co., Ltd.), it was confirmed that the evaluated Examples 14, 15, 16, and 18 had similar levels of repair coverage to the commercial product, indicating that the compositions of the present invention have excellent tissue repair effects.

[0093] Experimental Example 8: Comparison of efficacy with other polyhydric alcohols In order to compare the efficacy of Example 1, which was produced using glycerin, with Examples 2 to 7, which were produced using other polyhydric alcohols instead of glycerin, the properties of these were compared and shown in FIG.

[0094] As a result, as shown in Figure 9, in the case of Examples 4 to 6 in which other polyhydric alcohols were used, a large amount of bubbles were generated during the production of the liquid composition, which may increase the probability of defective products being produced during subsequent product production, and it was confirmed that this cannot be used as a tissue repair material.

[0095] Furthermore, the complex viscosity of Examples 1 to 3 and Example 7, in which no bubbles were generated, and purified water was evaluated in the same manner as in Experimental Example 2. The results are shown in Table 8 below.

[0096] [Table 8]

[0097] As a result, as shown in Table 8, it was confirmed that Example 7 could not be used as a biomaterial for tissue repair because the viscosity was so low that it was close to the level of purified water.

[0098] The above results confirm that the tissue repair composition containing the DNA fragment mixture and polyhydric alcohol of the present invention not only has excellent tissue repair effects, but also has moisturizing effects, especially when combined in a specific content range. These results suggest that the composition provides moisture to adjacent tissues without excessively adsorbing moisture from the tissues upon injection, and does not cause dryness in the surrounding tissues but rather alleviates the dryness, resulting in a high engraftment rate and a good moisturizing effect.

[0099] From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are merely illustrative and not limiting. The scope of the present invention should be interpreted as including within the meaning and scope of the claims below, and all modifications and variations derived from the equivalent concepts thereof, rather than the above detailed description.

Claims

1. A tissue repair composition comprising a DNA fragment mixture; and a C3 or C4 polyhydric alcohol, The DNA fragment mixture is contained in an amount of 2 to 5% by weight of the total composition; The polyhydric alcohol is contained in an amount of 0.5 to 4% by weight of the total composition, The composition for tissue repair, wherein the polyhydric alcohol is at least one selected from the group consisting of glycerin, propylene glycol, and butylene glycol.

2. The tissue repair composition according to claim 1 , wherein the composition has tissue moisturizing ability.

3. The tissue repair composition of claim 1 , wherein the composition increases the water content of tissue upon injection into the tissue.

4. The tissue repair composition according to claim 1, wherein the DNA fragment mixture and the polyhydric alcohol are contained in a weight ratio of 10:1 to 1:

2.

5. The tissue repair composition according to claim 1, wherein the DNA fragment mixture and the polyhydric alcohol are contained in a weight ratio of 6:1 to 1:

1.

6. The tissue repair composition of claim 1 , wherein the DNA fragment mixture is a polynucleotide (PN), a polydeoxyribonucleotide (PDRN), or a mixture thereof.

7. 2. The tissue repair composition of claim 1, wherein the DNA fragment mixture has a molecular weight of 50 to 10,000 kDa.

8. A biomaterial for tissue repair comprising the composition of any one of claims 1 to 7.

9. A filler composition comprising: a DNA fragment mixture; and a C3 or C4 polyhydric alcohol, The DNA fragment mixture is contained in an amount of 2 to 5% by weight of the total composition; The polyhydric alcohol is contained in an amount of 0.5 to 4% by weight of the total composition, The filler composition, wherein the polyhydric alcohol is at least one selected from the group consisting of glycerin, propylene glycol, and butylene glycol.

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