Biomaterial composition for tissue repair comprising mixture of DNA fragments and polyol

Abstract

The present disclosure provides a composition for tissue repair, the composition comprising a DNA fragment mixture and a C3 or C4 polyol; a filler composition; methods of repairing tissue using the compositions; and its use in tissue repair.

Description

Technical field

[0001] The present disclosure relates to a composition for tissue repair, comprising a mixture of DNA fragments and a C3 or C4 polyol; a filler composition; a tissue repair method using the composition; and use of the composition in tissue repair. [Background Technology]

[0002] With growing interest in combating aging, an increasing number of procedures are being used to compensate for defects in the body, including those affecting joints, cardiovascular health, and skin. For example, cosmetic surgeries aimed at improving wrinkles or other cosmetic conditions are among these procedures. In recent years, the use of injections of highly biocompatible materials has become increasingly common in this area, replacing damaged tissue and increasing the volume of desired areas.

[0003] For example, there are filler compositions with hyaluronic acid as the main component. However, some hyaluronic acid fillers are difficult to inject into the skin due to their high viscosity and low elasticity. Even after injection, they do not retain their injected form (shape) for long, and their shape retention period is short. To improve this, various compounds are being added (U.S. Patent No. 11,154,481), but it is difficult to minimize side effects while also improving the problem. [Summary of the invention]

[0004]

Technical Issues

[0005] There remains a need to develop improved biomaterials for tissue repair.

[0006]

Technical solution

[0007] The present disclosure provides a composition for tissue repair, comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is 0.5 wt% to 4 wt% relative to the total weight of the composition.

[0008] Another object of the present disclosure is to provide a filler composition comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is in an amount of 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is in an amount of 0.5 wt% to 4 wt% relative to the total weight of the composition.

[0009] Another object of the present disclosure is to provide a method for repairing tissue, comprising the step of administering the tissue repair composition or filler composition to a subject.

[0010] Another object of the present disclosure is to provide a composition for tissue repair, comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is 0.5 wt% to 4 wt% relative to the total weight of the composition.

[0011]

Technical Effect

[0012] The tissue repair biomaterial disclosed herein not only has the ability to repair tissue, but also has a moisturizing effect, thereby having the effect of not giving the tissue a dry feeling.

Brief description of the attached figure

[0014] Figure 1 Results from animal trials verifying the effects of increasing water content are shown;

[0015] Figure 2 shows the normalized results of the injection force test of the prepared comparative examples and examples;

[0016] Figures 3 to 6 The phase angle test results of the prepared comparative examples and embodiments are shown;

[0017] Figure 7 The test results of biodegradability of the prepared comparative examples and examples are shown;

[0018] Figure 8 shows the results of comparing the height and breadth of the injection site after injection of the prepared liquid compositions of Comparative Examples and Examples; and

[0019] Figure 9 Results comparing the properties of each composition when a liquid composition was prepared are shown.

[0020] [Detailed description of preferred embodiments]

[0021] The present disclosure is described in detail below. At the same time, each description and embodiment disclosed in this disclosure may also be applicable to other descriptions and embodiments. In other words, all combinations of the various elements disclosed in this disclosure are within the scope of this disclosure. Furthermore, the scope of this disclosure is not limited by the specific description below. Furthermore, many papers and patent documents are referenced and cited in this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to further clarify the level and scope of the subject matter involved in this disclosure.

[0022] One aspect of the present disclosure provides a composition for tissue repair, comprising a mixture of DNA fragments and an alcohol. Specifically, the alcohol can be a polyol, more specifically, a C3 or C4 polyol.

[0023] In one embodiment, the composition for tissue repair of the present disclosure is characterized by comprising a mixture of DNA fragments and a C3 or C4 polyol as active ingredients.

[0024] As used herein, the term "DNA fragment mixture" includes DNA corresponding to a biopolymer composed of phosphate, four bases, and deoxyribose, and refers to a mixture of nucleic acid fragments having a molecular weight within a predetermined range and existing as nucleotide polymers. The DNA fragment mixture may exist as a mixture of fragments with lower molecular weights, but is not limited thereto, and is used interchangeably with terms such as "DNA fragment," "DNA component," "nucleic acid fragment," and "nucleic acid fragment mixture."

[0025] In one embodiment, the DNA fragment mixture of the present disclosure can be a polynucleotide (PN), a polydeoxyribonucleotide (PDRN), or a mixture thereof.

[0026] As used herein, the term "polynucleotide" is referred to as "PN" and may refer to a DNA or RNA chain, which is a polymer of nucleotides in which nucleotide units (monomers) are linked together in a chain by covalent bonds. In addition, as used herein, the term "polydeoxyribonucleotide" is referred to as "PDRN" and may be a class of low-molecular-weight DNA complexes with a specific molecular weight, but is not limited thereto. For example, compared to polydeoxyribonucleotides, polynucleotides may have a relatively longer nucleic acid length or a larger molecular weight, can be used as a raw material for medical devices, have a physical support effect of cell fixation and lubrication and buffering, and polydeoxyribonucleotides can be used as a pharmaceutical raw material for cell proliferation and tissue regeneration, but is not limited thereto.

[0027] In one embodiment, the liquid composition of the DNA fragment mixture of the present disclosure may include a buffer, and the buffer solution may be any one or more selected from the following: sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dodecahydrate, sodium chloride, magnesium chloride, potassium chloride and phosphate-buffered saline, or N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid (HEPES), but is not limited thereto.

[0028] The DNA fragment mixture according to any of the above embodiments can be obtained by extracting from the testicles or semen of a fish. Specifically, the fish may be salmon. More specifically, it may be salmon or trout, but is not limited thereto.

[0029] The mixture of DNA fragments according to any of the above embodiments may have a molecular weight of about 1 kDa to about 100,000 kDa, about 5 kDa to about 50,000 kDa, about 50 kDa to about 10,000 kDa, or about 50 kDa to about 1,500 kDa.

[0030] In any of the above embodiments, the DNA fragment mixture disclosed herein may be a polynucleotide (PN), but is not limited thereto.

[0031] The content of the DNA fragment mixture according to any of the above embodiments may be 2 wt% to 7 wt% relative to the total weight of the tissue repair composition, particularly, 2 wt% or more and less than 7 wt%, 2 wt% to 6 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 7 wt%, 3 wt% or more and less than 7 wt%, 3 wt% to 6 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, 4 wt% to 7 wt%, 4 wt% or more and less than 7 wt%, 4 wt% to 6 wt%, 4 wt% to 5 wt%, 5 wt% to 7 wt%, 5 wt% or more and less than 7 wt%, 5 wt% to 6 wt%, 6 wt% to 7 wt%, or 6 wt% or more and less than 7 wt%.

[0032] The C3 or C4 polyol of the present disclosure refers to an alcohol having 3 or 4 carbon atoms and having two or more hydroxyl groups (—OH).

[0033] The content of the polyol according to any of the above embodiments may be 0.5 wt % to 8 wt % relative to the total weight of the tissue repair composition, particularly 0.5 wt % or more and less than 8 wt %, 0.5 wt % to 7 wt %, 0.5 wt % to 6 wt %, 0.5 wt % to 5 wt %, 0.5 wt % to 4 wt %, 0.5 wt % to 3 wt %, 0.5 wt % to 2 wt %, 0.5 wt % to 1 wt %, 1 wt % or more and less than 8 wt %, 1 wt % to 7 wt %, 1 wt % to 6 wt %, 1 wt % to 5 wt %, 1 wt % to 4 wt %, 1 wt % to 3 weight %, 1 weight % to 2 weight %, 2 weight % or more and less than 8 weight %, 2 weight % to 7 weight %, 2 weight % to 6 weight %, 2 weight % to 5 weight %, 2 weight % to 4 weight %, 2 weight % to 3 weight %, 3 weight % or more and less than 8 weight %, 3 weight % to 7 weight %, 3 weight % to 6 weight %, 3 weight % to 5 weight %, 3 weight % to 4 weight %, 4 weight % or more and less than 8 weight %, 4 weight % to 7 weight %, 4 weight % to 6 weight %, 4 weight % to 5 weight %, 5 weight % or more and less than 8 weight %, 5 weight % to 7 weight %, or 5 weight % to 6 weight %.

[0034] The polyol according to any one of the above embodiments may be any one or more selected from the group consisting of glycerol, propylene glycol, and butylene glycol, but is not limited thereto.

[0035] In the present disclosure, it has been confirmed that polyol alone cannot be used for tissue repair purposes, while the combination of a DNA fragment mixture and C3 or C4 polyol can reduce viscosity, thereby increasing the ease of injection.

[0036] Furthermore, the combination of a DNA fragment mixture with polyols such as polyethylene glycol (PEG) and triethylene glycol generates a large amount of foam during the preparation of its liquid composition, which increases the possibility of defective products in future product production, or the viscosity approaches zero, making it unusable for tissue repair. In contrast, the combination of the DNA fragment mixture of the present disclosure and C3 or C4 polyols has been shown to have significantly lower likelihood of such problems.

[0037] At the same time, the tissue repair composition of the present disclosure may have the ability to moisturize tissue.

[0038] As used herein, the term "tissue moisturizing ability" refers to increasing the moisture content of a tissue. The tissue moisturizing ability of the present disclosure may mean that, when a composition of the present disclosure is injected into a tissue, the moisture content of the tissue is increased, compared to the moisture content of the tissue when the composition of the present disclosure is not injected into the tissue. This moisturizing ability may aid in tissue repair, with high engraftment rates and moisturizing effects, while increasing the moisture content in the tissue without causing a dry sensation in the surrounding tissue, but rather relieving the dryness.

[0039] The composition for tissue repair according to any one of the above embodiments can increase the moisture content of tissue when injected into the tissue.

[0040] Examples of such tissues may include, but are not limited to, skin.

[0041] In one embodiment of the present disclosure, a tissue repair composition further comprising a C3 or C4 polyol (particularly, at a specific content) was demonstrated to not only exhibit excellent tissue repair effects but also increase moisture content when injected into tissue, compared to a mixture comprising a DNA fragment alone. This demonstrates that, upon injection, the disclosed composition does not excessively absorb moisture from surrounding tissue, but rather provides moisture to surrounding tissue, thereby alleviating dryness and providing tissue repair effects, with a high implantation rate and good moisture content.

[0042] In particular, it was confirmed that when the composition contains a DNA fragment mixture and a C3 or C4 polyol (wherein the content of the DNA fragment mixture is 2% to 5% by weight relative to the total weight of the composition, and the content of the polyol is 0.5% to 4% by weight relative to the total weight of the composition), it has a significant moisturizing effect, and the tissue repair effect is also very good within the same range. This shows that within the above content combination range, the composition does not cause dryness to the surrounding tissue, but instead alleviates dryness, has a tissue repair effect, and has a good moisturizing effect.

[0043] The tissue repair composition according to any one of the above embodiments may include the DNA fragment mixture and the polyol in a weight ratio of 10:1 to 1:2, but is not limited thereto.

[0044] In any of the above embodiments, the tissue repair composition of the present disclosure may comprise the DNA fragment mixture and the polyol in a weight ratio of about 10:1 to about 1:2, about 10:1 to about 1:1, about 8:1 to about 1:2, about 8:1 to about 1:1, about 6:1 to about 1:2, about 6:1 to about 1:1, about 5:1 to about 1:2, about 5:1 to about 1:1, about 4:1 to about 1:2 or about 4:1 to about 1:1, particularly in a weight ratio of about 10:1 to about 1:2, about 10:1 to 1:1 or about 6:1 to 1:2.

[0045] The term "about" may include not only the exact number cited after the term, but also a range that is close to or approximately that number. Whether any number is close to or approximately the specific number presented can be determined by considering the context in which the number is presented. For example, the term "about" may refer to a range of -10% to +10% of a given number. As another example, the term "about" may refer to a range of -5% to +5% of a given number. As another example, the term may refer to a range including, but not limited to, ±0.5, ±0.4, ±0.3, ±0.2, ±0.1, etc.

[0046] In the present disclosure, even if the term "about" is omitted before a numeral, it is obvious that the present disclosure includes a range without the omission of the term.

[0047] Meanwhile, as used herein, the term "for tissue repair" means that it can be used to replace, repair and / or reconstruct human tissues and organs, such as blood vessels, heart, diaphragm, fascia and / or skin, etc.

[0048] The tissue repair composition disclosed herein can be used as a tissue repair biomaterial, and tissue repair biomaterial refers to a biologically derived material used to replace, repair and reconstruct human tissues and organs such as blood vessels, heart, diaphragm, fascia, skin, etc., and is not limited to cosmetic fillers, and may refer to a tissue repair biomaterial specified by the Ministry of Food and Drug Safety.

[0049] The tissue repair composition of the present disclosure may be a liquid composition or an injectable composition, but is not limited thereto.

[0050] As used herein, the term "injectable" refers to a material having the necessary properties for administering the composition to a subject using an injection device having a needle.

[0051] As used herein, the term "administer" refers to introducing the present disclosure into a subject by any appropriate method, and administration can be performed by various routes, such as application, subcutaneous administration, dermal administration, blood vessels, biological membranes, tissue fibers, synovial fluid, etc., as long as it can reach the target tissue. The dosage form can be used for, but is not limited to, topical application, subcutaneous injection, skin injection, intravascular injection, intramuscular injection, intraarticular injection, intratendon injection, and intraligament injection. The ideal dosage of the disclosed composition may vary depending on the subject's condition.

[0052] The tissue repair composition according to the present disclosure may exhibit a viscosity range suitable for injection into the target tissue.

[0053] Furthermore, as used herein, the term "viscosity" refers to a property of a fluid, namely, a flow having viscosity, which is resistance to flow. The viscosity can be expressed as viscosity, particularly complex viscosity (η*, Pa·s).

[0054] In any of the above embodiments, the tissue repair composition of the present disclosure may exhibit a complex viscosity of 1 Pa·s to 2,000 Pa·s, in particular, 5 Pa·s to 2,000 Pa·s, 8 Pa·s to 2,000 Pa·s, 1 Pa·s to 1,500 Pa·s, 5 Pa·s to 1,500 Pa·s, 8 Pa·s to 1,500 Pa·s, 1 Pa·s to 1,300 Pa·s, 5 Pa·s to 1,300 Pa·s, or 8 Pa·s to 1,300 Pa·s.

[0055] The viscosity range of the tissue repair composition used as a general biomaterial for tissue repair is from about 1 Pa·s to about 8,000 Pa·s. When the viscosity is within the above range, the composition can be naturally transplanted into the tissue in the body after application. Generally speaking, when the viscosity range of the tissue repair composition is about 1 Pa·s or less, although it is implanted in the body, its ability to form its own shape is low, and therefore, the composition may not be able to generate volume as a biomaterial for tissue repair, and it may be difficult to control the injection volume, for example, a large amount of injection liquid can be injected even with a small force. In addition, when the viscosity range is higher, for example, about 8,000 Pa·s or more, it is difficult to squeeze out the syringe when injecting the composition into the body through a syringe, and excessive force may be required during the injection process, making it difficult to inject an accurate amount and difficult to accurately control the injection volume, which may cause side effects.

[0056] When applied at a rate of 50 mm / min, the tissue repair composition of the present disclosure can be injected with an injection force of 0 or greater 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. For example, the above injection force can be injected through a 33-gauge needle, but is not limited thereto. Specifically, according to the Approval and Review Guidelines for Plastic Surgery Fillers, it may be appropriate to set the injection force to 40 N or less.

[0057] The tissue repair composition of the present disclosure may further include one or more compounds selected from the group consisting of anesthetics, vitamins, amino acids, metals, antioxidants, and mineral salts, but is not limited thereto.

[0058] The tissue repair composition of the present disclosure may further comprise any suitable excipient commonly used in the art, and such excipient may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer or an isotonic agent, but is not limited thereto.

[0059] Another aspect of the present disclosure provides a biomaterial for tissue repair, wherein the biomaterial comprises the composition for tissue repair of the present disclosure.

[0060] The composition for tissue repair and the biomaterial for tissue repair are as described in other aspects.

[0061] Another aspect of the present disclosure provides a filler composition comprising a DNA fragment mixture and an alcohol. Specifically, the alcohol can be a polyol, more specifically, a C3 or C4 polyol.

[0062] Furthermore, the DNA fragment mixture may be contained in an amount of 2 to 5 wt % relative to the total weight of the composition, and the polyol may be contained in an amount of 0.5 to 4 wt % relative to the total weight of the composition.

[0063] As used herein, the term "filler," which is a material for tissue repair, refers to a medical device that is injected into the skin to restore volume, etc., and has the working principle of maintaining skin volume through physical repair.

[0064] The DNA fragment mixture, the polyol, etc. are as described in other aspects. The filler composition can be a specific embodiment of the tissue repair composition, and the description of the tissue repair composition disclosed in the present invention (DNA fragment mixture, polyol, its content, weight ratio, tissue moisturizing ability, liquid composition, injectable composition, administration method, appropriate range of injection viscosity, etc.) can all be applied to the filler composition.

[0065] The filler composition of the present disclosure may further include one or more compounds selected from the group consisting of anesthetics, vitamins, amino acids, metals, antioxidants, and mineral salts, but is not limited thereto.

[0066] The filling composition of the present disclosure may further comprise any suitable excipient commonly used in the art, and such excipient may be, for example, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer or an isotonic agent, but is not limited thereto.

[0067] Another aspect of the present disclosure provides a method of repairing tissue comprising the step of administering a tissue repair composition or filler composition to a subject.

[0068] Administration, tissue repair, compositions for tissue repair, filler compositions, etc. are as described elsewhere.

[0069] As used herein, the term "subject" refers to all animals including humans that need or may need tissue repair, such as rats, mice, livestock, etc. Specifically, the subject may be a mammal, including humans.

[0070] Another aspect of the present disclosure provides use of a composition in tissue repair, the composition comprising a DNA fragment mixture and a C3 or C4 polyol, wherein the content of the DNA fragment mixture is 2 wt% to 5 wt% relative to the total weight of the composition, and the content of the polyol is 0.5 wt% to 4 wt% relative to the total weight of the composition.

[0071] The DNA fragment mixture, the polyol, and the tissue repair are as described in other aspects.

[0072] [Modes for Carrying Out the Invention]

[0073] The present disclosure will be described in more detail below by way of illustrative embodiments. However, the following illustrative embodiments are merely illustrative of preferred embodiments of the present disclosure and are not intended to limit the scope of the present disclosure. Furthermore, technical matters not described in this specification can be fully understood and easily implemented by those skilled in the art of the present disclosure or similar technical fields.

[0074] [Preparation Example: Preparation of a Tissue Repair Biomaterial Containing a DNA Fragment Mixture and Polyol]

[0075] The DNA fragment mixture is added to a buffer and dissolved in a thermomixer at a high temperature of 60° C. to 80° C. to prepare a DNA fragment mixture solution. A polyol is added to the DNA fragment mixture solution prepared in the thermomixer at 60° C. to 80° C., mixed, and then the temperature of the mixed solution is lowered to room temperature to prepare a liquid composition.

[0076] At this time, polynucleotide (PN; manufacturer: PharmaResearch Co., Ltd.) was used as a representative example of the DNA fragment mixture, and the names and concentrations of the samples are shown in Tables 1 and 2 below.

[0077]

Table 1

[0078]

[0079]

[0080]

Table 2

[0081]

[0082] *Example 10 has the same composition and content as Example 1.

[0083] [Experimental Example 1: Verifying the moisturizing effect through animal testing]

[0084] A skin water loss model was prepared as a representative example using mouse tissue. At this time, the model was prepared with reference to a known 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).

[0085] The liquid composition prepared in the preparation example was injected into the body of the prepared animal model, and then the hydration measurement device ( The moisture content of mouse skin was measured using a CM 825 (Courage+Khazaka electronic GmbH, Germany) at 25±5°C and 50%±5% RH.

[0086] Results, such as Figure 1 As shown, it was confirmed that the examples comprising a mixture of glycerol and DNA fragments in a specific content or ratio imparted higher hydration (moisturizing effect) to the tissue.

[0087] In particular, it was confirmed that a composition containing a DNA fragment mixture in an amount of 2% to 5% by weight relative to the total weight of the composition and a polyol in an amount of 0.5% to 4% by weight relative to the total weight of the composition is of key significance for the moisturizing effect, and as described below, it was also confirmed that the composition has excellent tissue repair effects in terms of viscosity, injection force, injection feeling, biodegradability, etc. within the same content range, indicating that within the above-mentioned content combination range, a tissue repair effect with a higher implantation rate and better moisturizing effect may be obtained.

[0088] [Experimental Example 2: Viscosity Test]

[0089] 48 hours after preparation, the complex viscosity (η*, Pas; hereinafter referred to as viscosity) of the liquid compositions prepared in Comparative Examples 1-6 and Examples 8-33 for the DNA fragment mixture alone, glycerol alone, and the combination of the DNA fragment mixture and glycerol was measured 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, frequency: 0.1 Hz, shear strain: 0.5%, analysis program: rSpace for Kinexus. The results are shown in Table 3 below.

[0090]

Table 3

[0091]

[0092]

[0093] As shown in Table 3, it was confirmed that glycerol alone (Comparative Example 6) had a viscosity similar to that of pure water and was therefore unusable for tissue repair, whereas the viscosity of the combination of the DNA fragment mixture and glycerol (Examples 8 to 33) was lower than that of the DNA fragment mixture alone (Comparative Examples 1 to 5). This suggests that the combination of the DNA fragment mixture and glycerol (Examples 8 to 33) may increase the ease of injection.

[0094] [Experimental Example 3: Injection Force Test]

[0095] The injection force was measured for Comparative Examples 1 to 5 and Examples 8 to 33, except for glycerol alone (Comparative Example 6) which was verified to be unusable for tissue repair in Experimental Example 2.

[0096] The injection force represents the force (N) required to inject the injectable solution and is measured at an injection speed of 50 mm / min. The liquid compositions prepared in all the embodiments and comparative examples for examining the injection force were measured using an injection force tester (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, South Korea) under the following conditions: measurement temperature of 25±2°C, injection needle: JBP Korea (South Korea), 33G nanoneedle, injection speed: 50 mm / min. The results are shown in Tables 4 and 5 below. Figure 2 shown.

[0097]

Table 4

[0098]

[0099]

[0100] The injection force values ​​of the compositions without glycerol (Comparative Examples 1 to 5) were replaced with 100%, and the values ​​of the Examples were normalized to the values ​​of the Comparative Examples based on the same content of the DNA fragment mixture. Figure 2 The values ​​are shown as %.

[0101] The results are shown in Table 4 and Figure 2 As shown, it was confirmed that the injection force was weakened in the case of combining with glycerol compared with the DNA fragment mixture alone, and it was confirmed that even though the comparative example had a higher injection force, the example having the combination of the DNA fragment mixture and glycerol had a higher injection force control effect.

[0102] [Experimental Example 4: Injection Sensation Test]

[0103] Excluding glycerol alone (Comparative Example 6), which was proven to be useless for tissue repair in Experimental Example 2, and excluding Examples 32 and 33, which did not meet the injection force requirement of 40N or less stipulated in the approval guidelines for plastic surgery fillers, the injection feeling was evaluated for representative comparative examples and examples.

[0104] A blind test was conducted on 4 independently recruited subjects, who evaluated the injection sensation by releasing each composition of the comparative example and experimental example into a culture dish using a syringe needle (33-gauge nano needle) used in the actual product. Except for using a device (equipment) for measuring injection force, all other conditions were the same as those in the injection force test. Easier injection (more comfortable) was scored as 1 point, and more difficult injection (more uncomfortable) was scored as 5 points. The results are shown in Tables 5 and 6 below. Table 5 shows the number of people who rated each score.

[0105]

Table 5

[0106]

[0107]

Table 6

[0108]

[0109] As shown in Tables 5 and 6, in the case of combination with glycerol (Example 8, etc.), the actual injection feeling test score was lower, indicating that the injection feeling was superior compared with the DNA fragment mixture alone (Comparative Examples 1, 2, and 4).

[0110] [Experimental Example 5: Phase Angle Test]

[0111] The phase angle (δ, °) of each liquid composition prepared in Examples and Comparative Examples was measured using a rheometer (NETZSCH (Germany), Kinexus Ultra+ rheometer) 48 hours after preparation. Specifically, the phase angle was measured under the following conditions: measurement temperature was 25°C, geometry used was PU20, gap was 1.0 mm, frequency was 0.1 Hz, shear strain was 0.5%, and analysis program was rSpace for Kinexus. The results are shown in FIG. Figures 3 to 6 shown.

[0112] Results, such as Figures 3 to 6 As shown, the phase angle increased in the case of combining with glycerol (Examples 8 to 31) compared with the DNA fragment mixture alone (Comparative Examples 1 and 4), indicating that the ease of injection can be increased by further increasing the fluidity.

[0113] [Experimental Example 6: Comparison of biodegradability of bioremediation materials in the presence and absence of a DNA fragment mixture and polyol]

[0114] Liquid compositions were injected into mice respectively, each of which contained a mixture of DNA fragments and / or polyols (glycerol, propylene glycol, butylene glycol) within the range of Comparative Example 6 and Example 28. The mice used were SKH-1 hairless mice (6 weeks old, female) and were raised under the following conditions: temperature 22±2°C, relative humidity 50±10%, and free access to food and water. The experimental period included a 1-week acclimatization period, followed by sample injection, and euthanasia 60 hours after injection. A volume of 100 μL was injected intradermally into the dorsal area of ​​the mouse. In addition, volume changes at the injection site after sample injection were observed. The results of the examination using 3D photo simulation (Primos, Canfield (USA)) are shown as follows Figure 7 shown.

[0115] Results, such as Figure 7 As shown, it was confirmed that the individual polyols (glycerol, propylene glycol, butylene glycol) completely decomposed immediately after injection and could not be used for tissue repair purposes. However, it was confirmed that the combination of the DNA fragment mixture and the polyols (glycerol, propylene glycol, butylene glycol) was still present even after 60 hours, indicating that they are suitable as biomaterials for repair.

[0116] [Experimental Example 7: Comparison of height and width after injection of liquid composition]

[0117] If a tissue repair biomaterial spreads too widely after injection into the body, the repair effect may be minimal, whereas if the width is narrow and the height is high, it may be too prominent visually and aesthetically, causing problems such as lumps or hives. Therefore, the width and height after injection are evaluated.

[0118] In this experiment, SKH-1 hairless mice (6 weeks old, female) were used. The mice were housed under the following conditions: temperature 22 ± 2°C, relative humidity 50 ± 10%, with food and water available ad libitum. The experimental period consisted of a 1-week acclimation period, followed by sample injection, with measurements taken immediately after injection. The mice were euthanized after 7 days. A volume of 100 μL was injected intradermally into the dorsal region of the mice.

[0119] To this end, each liquid composition of the comparative example and the embodiment prepared in the preparation example was injected into mice, and the height and width of the injected sample were measured using a vernier caliper (MITUTOYO, Japan) and analyzed using ImageJ software. The results are shown in FIG. Figure 8 and as shown in Table 7.

[0120]

Table 7

[0121]

[0122] As shown in Table 7 and Figure 8As shown, compared with a commercial product (Rejuran; RJR; Pharma Research Co., Ltd.), Test Examples 14, 15, 16 and 18 were confirmed to have a repair range level similar to that of the commercial product, indicating that the composition of the present disclosure has an excellent tissue repair effect.

[0123] [Experimental Example 8: Comparison of efficacy with other polyols]

[0124] In order to compare the efficacy of Example 1 prepared using glycerol and Examples 2 to 7 prepared using other polyols instead of glycerol, their properties were compared and Figure 9 Displayed in.

[0125] Results, such as Figure 9 As shown, Examples 4 to 6 using other polyols generated a large amount of foam during the preparation of the liquid composition, which may increase the possibility of defective products in future product production, thereby confirming that they cannot be used as materials for tissue repair.

[0126] Furthermore, the results of evaluating the complex viscosity in the same manner as in Examples 1 to 3, Experimental Example 2 of Example 7, and purified water that does not generate foam are shown in Table 8 below.

[0127]

Table 8

[0128]

[0129] 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 its viscosity was almost as low as that of pure water.

[0130] These results demonstrate that the tissue repair composition comprising a mixture of DNA fragments and a polyol disclosed herein not only exhibits excellent tissue repair effects but also exhibits a moisturizing effect within a specific range of the composition content. These results demonstrate that upon injection, the composition does not excessively absorb moisture from surrounding tissues, but instead provides moisture to surrounding tissues, thereby alleviating dryness rather than causing it to dry out. Furthermore, the composition exhibits a high implantation rate and excellent moisturizing effects.

[0131] Based on the above description, it will be understood by those skilled in the art that the present disclosure can be implemented in different specific forms without changing its technical spirit or basic features. In this regard, it should be understood that the above embodiments are not restrictive, but illustrative in all aspects. The scope of disclosure is defined by the appended claims, rather than by the description preceding them, and therefore, the scope of the claims and all changes and modifications within the scope, or equivalents of such scope, are intended to be included in the claims.

Claims

1. A composition for tissue repair, comprising: DNA fragment mixture; and C3 or C4 polyols, in The content of the DNA fragment mixture is 2% to 5% by weight relative to the total weight of the composition. The content of the polyol is 0.5 wt% to 4 wt% relative to the total weight of the composition, and The polyol is selected from any one or more of the following: glycerol, 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 according to claim 1, wherein The composition, when injected into tissue, increases the moisture content of the tissue.

4. The tissue repair composition according to claim 1, wherein The weight ratio of the DNA fragment mixture to the polyol is 10:1 to 1:

2.

5. The tissue repair composition according to claim 1, wherein The weight ratio of the DNA fragment mixture to the polyol is 6:1 to 1:

1.

6. The tissue repair composition according to claim 1, wherein The DNA fragment mixture is polynucleotide (PN), polydeoxyribonucleotide (PDRN) or a mixture thereof. The composition for tissue repair according to claim 1 , wherein the molecular weight of the DNA fragment mixture is 50 kDa to 10,000 kDa.

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

9. A filling composition comprising: DNA fragment mixture; and C3 or C4 polyols, in The content of the DNA fragment mixture is 2% to 5% by weight relative to the total weight of the composition. The content of the polyol is 0.5 wt% to 4 wt% relative to the total weight of the composition, and The polyol is selected from any one or more of the following: glycerol, propylene glycol and butylene glycol.

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