PDRN non-crosslinked sodium hyaluronate gel composition, preparation method, related product and application

Abstract

The invention provides a PDRN non-crosslinked sodium hyaluronate gel composition, a preparation method, a related product and application, and belongs to the technical field of medicines, medical instruments and cosmetics. The PDRN gel composition disclosed by the invention is prepared from the following components in parts by weight: 5 to 15 parts of sodium hyaluronate 1, 1 to 3 parts of sodium hyaluronate 2, 1 to 2.7 parts of PDRN, 0.05 to 0.15 part of phytic acid, 0.025 to 0.075 part of zinc chloride and 200 to 300 parts of water. Wherein the molecular weight of the sodium hyaluronate 1 is 1,000 kDa to 2,000 kDa; the molecular weight of the sodium hyaluronate 2 is less than 10kDa. The composition provided by the invention can be used for preparing PDRN sodium hyaluronate gel which does not contain a chemical cross-linking agent, and controlled release and better storage stability of PDRN can be realized.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, medical equipment and cosmetics, and relates to a PDRN non-cross-linked sodium hyaluronate gel composition, a preparation method, related products and applications. Background Art

[0002] Sodium hyaluronate is a sodium salt of glucuronic acid, which exists naturally in mammalian connective tissue, skin, eyes and joint fluid, and is an important biopolymer. Its corresponding acid is hyaluronic acid, also known as hyaluronic acid, which is one of the main components of the extracellular matrix. Hyaluronic acid and sodium hyaluronate have good biocompatibility and have been widely used in beauty, cosmetics, daily chemicals and other fields.

[0003] In order to improve the physical and chemical properties of sodium hyaluronate and adapt to the characteristics of products containing sodium hyaluronate in different scenarios, the microstructure of sodium hyaluronate is often modified by chemical cross-linking. Since sodium hyaluronate contains active groups such as carboxyl (sodium salt) and hydroxyl, it is often cross-linked with chemical reagents that can react chemically with them. For example, Mi Pengcheng et al. provided a technique for preparing cross-linked sodium hyaluronate using divinyl sulfone as a cross-linking agent in the article "Preparation and Biocompatibility of Divinyl Sulfone Cross-linked Sodium Hyaluronate Gel" (Chinese Journal of Tissue Engineering Research and Clinical Rehabilitation, 2008, 12 (14): 4). The prepared sodium hyaluronate has good biocompatibility and its stability has been improved to a certain extent. However, the use of chemical cross-linking agents to covalently cross-link sodium hyaluronate introduces small molecules of cross-linking agents that do not exist in biological systems. Although the cross-linked sodium hyaluronate material can be degraded macroscopically (by naked eye), it does not mean that the molecular fragments containing the cross-linking agent after degradation will not produce biocompatibility risks. In addition, the degree of cross-linking reaction is limited, so there may be residual chemical cross-linking agents. All of these affect the biocompatibility of chemically cross-linked sodium hyaluronate materials.

[0004] Phytic acid, also known as inositol hexaphosphate and cyclohexanehexol hexaphosphate, is an organic phosphate compound extracted from plant seeds. Phytic acid is a natural small molecule with multiple phosphate groups in its chemical structure. It can produce intermolecular interactions with a variety of biological molecules such as proteins, polysaccharides, polypeptides, nucleic acids, etc. It is also a moisturizer and antioxidant and is widely used in the cosmetics industry. The interaction between phytic acid and biological macromolecules belongs to intermolecular interaction and does not affect the covalent structure of the biological macromolecules themselves. However, since the binding force of intermolecular interactions is relatively weak compared to covalent bonds, in a complex gel system containing a variety of biological macromolecules, the effect of phytic acid itself on the stability of the gel system is more complex and difficult to predict.

[0005] PDRN (polydeoxyribonucleotide), also known as "polydeoxyribonucleotide", is a class of naturally derived DNA derivatives, consisting of a mixture of DNA fragments with chain lengths of 50-2000 base pairs. At present, PDRN is mainly extracted and purified from salmon sperm cells. PDRN has shown definite effects in anti-inflammation, wound healing, tissue recovery, and anti-ischemia.

[0006] Chinese invention patent CN118873426A provides a PDRN-cross-linked sodium hyaluronate composition and its application, which includes PDRN, oxidized sodium hyaluronate, polyamino acid and deionized water. This technology uses sodium periodate to oxidize sodium hyaluronate, and the oxidized sodium hyaluronate contains aldehyde groups; then PDRN is cross-linked with the sodium hyaluronate containing aldehyde groups to form a PDRN-cross-linked sodium hyaluronate composition. Although this method does not add a chemical cross-linking agent, it changes the chemical structure of sodium hyaluronate, and the cross-linking position of the generated PDRN-cross-linked sodium hyaluronate is uncertain, which has a potential impact on the anti-inflammatory and tissue recovery properties of PDRN itself. Finally, the oxidative modification of the gel itself increases the oxidation value of the gel as a whole, which is not conducive to the manifestation of the anti-inflammatory and antioxidant effects of the gel.

[0007] In summary, the prior art has not yet provided a PDRN-sodium hyaluronate gel system that can exist stably without covalent cross-linking and without changing the covalent structure of each raw material. Summary of the invention

[0008] In view of this, in order to solve the problems existing in the prior art, the object of the present invention is to provide a PDRN non-cross-linked sodium hyaluronate gel composition, related products, preparation methods and applications.

[0009] To achieve the above-mentioned object of the invention, on the one hand, the present invention provides a PDRN non-cross-linked sodium hyaluronate gel composition, which is composed of the following components by weight: 5-15 parts of sodium hyaluronate 1, 1-3 parts of sodium hyaluronate 2, 1-2.7 parts of PDRN, 0.05-0.15 parts of phytic acid, 0.025-0.075 parts of zinc chloride and 200-300 parts of water; Among them, the molecular weight of sodium hyaluronate 1 is 1000kDa-2000kDa; the molecular weight of sodium hyaluronate 2 is less than 10kDa.

[0010] Preferably, the PDRN non-cross-linked sodium hyaluronate gel composition consists of the following components by weight: 8-12 parts of sodium hyaluronate 1, 1.5-2.5 parts of sodium hyaluronate 2, 1.4-2.3 parts of PDRN, 0.08-0.12 parts of phytic acid, 0.04-0.06 parts of zinc chloride and 200-250 parts of water.

[0011] More preferably, the PDRN non-cross-linked sodium hyaluronate gel composition consists of the following components in parts by weight: 10 parts of sodium hyaluronate 1, 2 parts of sodium hyaluronate 2, 1.85 parts of PDRN, 0.1 parts of phytic acid, 0.05 parts of zinc chloride and 236 parts of water.

[0012] Preferably, and as a specific example of the present invention, the molecular weight of the sodium hyaluronate 1 is 1500 kDa±1 kDa.

[0013] On the other hand, the present invention provides a method for preparing a PDRN non-cross-linked sodium hyaluronate gel using the above-mentioned PDRN non-cross-linked sodium hyaluronate gel composition, comprising the following steps: S1. Mix the formulated amount of sodium hyaluronate 2, PDRN, zinc chloride and water, and stir to obtain solution 1; S2, mixing the formulated amount of phytic acid with water to obtain solution 2; S3, adding solution 2 dropwise to the stirring solution 1 to obtain solution 3; S4. Mix the formulated amount of sodium hyaluronate 1 with the remaining amount of water, then add solution 3 and mix well to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0014] Preferably, in step S1, the weight of the water is 16-24 times, more preferably 20 times, the sum of the weights of sodium hyaluronate 2, PDRN and zinc chloride.

[0015] Preferably, in step S2, the weight of the water is 20-40 times, more preferably 30 times, the weight of the phytic acid.

[0016] Preferably, in step S1, the stirring speed is 800-1200 rpm, more preferably 1000 rpm.

[0017] Preferably, in step S1, the stirring time is 8-18 hours, more preferably 9 hours.

[0018] Preferably, in step S3, the dropping speed is 0.01-0.05 mL / min, more preferably 0.03 mL / min.

[0019] Preferably, in step S3, the stirring speed is 800-1200 rpm, more preferably 1000 rpm.

[0020] Preferably, in step S4, the mixing is specifically stirring for 24-48 hours, and more preferably, the stirring speed is 500-800 rpm.

[0021] In the above method, small molecular weight sodium hyaluronate, zinc chloride, PDRN and phytic acid can form submicron / micron-sized small crosslinks, which can stabilize and bind PDRN to a certain extent. On the other hand, after mixing with large molecular weight sodium hyaluronate, the above micron-sized small crosslinks can serve as nodes for large molecular weight sodium hyaluronate to connect through non-covalent interactions, that is, through the intermolecular interaction between the groups on the surface of the small crosslinks and the large molecular weight sodium hyaluronate, the gelling properties of the gel are improved. In this process, the covalent structure of PDRN and sodium hyaluronate does not change.

[0022] On the other hand, the present invention provides a PDRN non-cross-linked sodium hyaluronate gel prepared by the above method.

[0023] On the other hand, the present invention provides the use of the above-mentioned PDRN non-cross-linked sodium hyaluronate gel composition or the PDRN non-cross-linked sodium hyaluronate gel prepared by the above-mentioned method in the preparation of medicines, medical devices or cosmetics.

[0024] On the other hand, the present invention provides a medicine, which contains the above-mentioned PDRN non-cross-linked sodium hyaluronate gel composition or the PDRN non-cross-linked sodium hyaluronate gel prepared by the above-mentioned method.

[0025] On the other hand, the present invention provides a medical device, which contains the above-mentioned PDRN non-cross-linked sodium hyaluronate gel composition or the PDRN non-cross-linked sodium hyaluronate gel prepared by the above-mentioned method.

[0026] In the last aspect, the present invention provides a cosmetic product containing the above-mentioned PDRN non-cross-linked sodium hyaluronate gel composition or the PDRN non-cross-linked sodium hyaluronate gel prepared by the above-mentioned method.

[0027] The medicines, medical devices and cosmetics can be externally applied products acting on the skin, or products suitable for intradermal introduction and implantation, preferably in the form of dressings, emulsions, ointments, sprays, injections and microneedles.

[0028] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention provides a PDRN non-cross-linked sodium hyaluronate gel composition, which can obtain a PDRN non-cross-linked sodium hyaluronate gel having PDRN sustained-release properties, good storage stability and good biosafety by compounding PDRN with sodium hyaluronate of different molecular weights, zinc chloride and phytic acid.

[0029] (2) The present invention provides a method for preparing PDRN non-cross-linked sodium hyaluronate gel, which is simple and easy to implement and is conducive to industrial production. DETAILED DESCRIPTION

[0030] Terms and Claims of the Present Invention: 1. The articles “a”, “an” and “the” include plural referents unless expressly limited to one or more referents otherwise.

[0031] 2. Numerical range: Unless otherwise expressly stated, all ranges or ratios disclosed herein will be understood to include any and all sub-ranges or sub-ratios contained therein. For example, a range or ratio of 1 to 30 stated should be considered to be included between a minimum value of 1 and a maximum value of 30, and any sub-range or sub-ratio, integer, decimal, or sub-range or sub-ratio consisting of integers or decimals including the end points.

[0032] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0033] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0034] In the following examples, some of the reagents are from the following Table 1: Table 1

[0035] In the following examples, the instruments and equipment used are shown in Table 2: Table 2

[0036] Example 1 The preparation steps of PDRN non-cross-linked sodium hyaluronate gel are as follows.

[0037] S1. Add 200 mg of sodium hyaluronate (molecular weight < 10 kDa), 185 mg of PDRN, and 5 mg of zinc chloride in sequence to 8 mL (8 g) of deionized water under stirring at 1000 rpm. Stir for 9 h under closed conditions to fully disperse the mixture to obtain solution 1.

[0038] S2. Take 20 mg of phytic acid aqueous solution (50% by weight, containing 10 mg of phytic acid and 10 mg of water) and mix and dilute it with 290 mg of water to obtain solution 2.

[0039] S3. Aspirate solution 2 into a syringe, and use a microinjection pump to uniformly drop solution 2 in the syringe into solution 1 stirred at 1000 rpm at a speed of 0.03 mL / min to obtain solution 3.

[0040] S4. Mix 1000 mg of sodium hyaluronate (1500 kDa ± 1 kDa) with 15.3 g of water, stir overnight at 1000 rpm to mix evenly, then pour solution 3 into the mixed solution and mix evenly (stir at 600 rpm for 36 hours) to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0041] Example 2 The preparation steps of PDRN non-cross-linked sodium hyaluronate gel are as follows.

[0042] S1. Add 250 mg of sodium hyaluronate (molecular weight < 10 kDa), 230 mg of PDRN, and 4 mg of zinc chloride into 9.68 mL (9.68 g) of deionized water in sequence under stirring at 1000 rpm. Stir for 9 h under closed conditions to fully disperse them to obtain solution 1.

[0043] S2. Take 24 mg of phytic acid aqueous solution (50% by weight, containing 12 mg of phytic acid and 12 mg of water) and mix and dilute it with 348 mg of water to obtain solution 2.

[0044] S3. Aspirate solution 2 into a syringe, and use a microinjection pump to uniformly drop solution 2 in the syringe into solution 1 stirred at 1000 rpm at a speed of 0.03 mL / min to obtain solution 3.

[0045] S4. Mix 800 mg of sodium hyaluronate (1500 kDa ± 1 kDa) with 9.96 g of water, stir overnight at 1000 rpm to mix evenly, then pour solution 3 into the mixed solution and mix evenly (stir at 600 rpm for 36 h) to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0046] Example 3 The preparation steps of PDRN non-cross-linked sodium hyaluronate gel are as follows.

[0047] S1. Add 150 mg of sodium hyaluronate (molecular weight < 10 kDa), 140 mg of PDRN, and 6 mg of zinc chloride into 5.92 mL (5.92 g) of deionized water in sequence under stirring at 1000 rpm. Stir for 9 h under closed conditions to fully disperse them to obtain solution 1.

[0048] S2. Take 16 mg of phytic acid aqueous solution (50% by weight, containing 8 mg of phytic acid and 8 mg of water) and mix and dilute it with 232 mg of water to obtain solution 2.

[0049] S3. Aspirate solution 2 into a syringe, and use a microinjection pump to uniformly drop solution 2 in the syringe into solution 1 stirred at 1000 rpm at a speed of 0.03 mL / min to obtain solution 3.

[0050] S4. Mix 1200 mg of sodium hyaluronate (1500 kDa ± 1 kDa) with 18.84 g of water, stir overnight at 1000 rpm to mix evenly, then pour solution 3 into the mixed solution and mix evenly (stir at 600 rpm for 36 h) to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0051] Example 4 The preparation steps of PDRN non-cross-linked sodium hyaluronate gel are as follows.

[0052] S1. Add 300 mg of sodium hyaluronate (molecular weight < 10 kDa), 270 mg of PDRN, and 2.5 mg of zinc chloride to 9.16 mL (9.16 g) of deionized water in sequence under stirring at 1200 rpm. Stir for 8 h under closed conditions to fully disperse the mixture to obtain solution 1.

[0053] S2. Take 30 mg of phytic acid aqueous solution (50% by weight, containing 15 mg of phytic acid and 15 mg of water) and mix and dilute it with 585 mg of water to obtain solution 2.

[0054] S3. Aspirate solution 2 into a syringe, and use a microinjection pump to uniformly drop solution 2 in the syringe into solution 1 stirred at 800 rpm at a speed of 0.05 mL / min to obtain solution 3.

[0055] S4. Mix 500 mg of sodium hyaluronate (1500 kDa ± 1 kDa) with 10.24 g of water, stir at 800 rpm overnight, mix evenly, then pour solution 3 into the mixed solution, mix evenly (stir at 600 rpm for 36 h) to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0056] Example 5 The preparation steps of PDRN non-cross-linked sodium hyaluronate gel are as follows.

[0057] S1. Add 100 mg of sodium hyaluronate (molecular weight < 10 kDa), 100 mg of PDRN, and 7.5 mg of zinc chloride to 4.98 mL (4.98 g) of deionized water in sequence under stirring at 800 rpm. Stir for 18 h under closed conditions to fully disperse them to obtain solution 1.

[0058] S2. Take 10 mg of phytic acid aqueous solution (50% by weight, containing 5 mg of phytic acid and 5 mg of water) and mix and dilute it with 95 mg of water to obtain solution 2.

[0059] S3. Aspirate solution 2 into a syringe, and use a microinjection pump to uniformly drop solution 2 in the syringe into solution 1 stirred at 1200 rpm at a speed of 0.01 mL / min to obtain solution 3.

[0060] S4. Mix 1500 mg of sodium hyaluronate (1500 kDa ± 1 kDa) with 24.92 g of water, stir overnight at 1200 rpm to mix evenly, then pour solution 3 into the mixed solution and mix evenly (stir at 600 rpm for 36 h) to obtain PDRN non-cross-linked sodium hyaluronate gel.

[0061] The PDRN non-cross-linked sodium hyaluronate gels obtained in Example 1 to Example 5 are respectively recorded as Gel 1 to Gel 5, and the formulas of the PDRN non-cross-linked sodium hyaluronate gel compositions corresponding to Gel 1 to Gel 5 are summarized in Table 3: Table 3

[0062] Comparative Example 1 Compared with Example 1, in step S1, the amount of sodium hyaluronate (molecular weight <10 kDa) is changed to 600 mg; in step S4, the amount of sodium hyaluronate (1500 kDa ± 1 kDa) is changed to 600 mg, and the other conditions are the same.

[0063] Comparative Example 2 Compared with Example 1, in step S1, zinc chloride is replaced by calcium chloride of equal mass, and the rest are the same.

[0064] Comparative Example 3 Compared with Example 1, in step S1, zinc chloride is replaced by magnesium chloride of equal mass, and the rest are the same.

[0065] Comparative Example 4 Compared with Example 1, in step S1, zinc chloride is omitted, the amount of PDRN is changed to 190 mg, and the rest is the same.

[0066] Comparative Example 5 Compared with Example 1, in step S2, solution 2 is 310 mg of deionized water, and the rest is the same.

[0067] Comparative Example 6 Compared with Example 1, in step S3, solution 2 and solution 1 are mixed by direct mixing instead of dripping, and other conditions are the same.

[0068] Comparative Example 7 Compared with Example 1, in step S1, sodium hyaluronate (molecular weight <10 kDa) is replaced by sodium hyaluronate (Mw 100 kDa-200 kDa) of equal weight, and the rest are the same.

[0069] Comparative Example 8 Compared with Example 1, in step S4, sodium hyaluronate (1500 kDa±1 kDa) is replaced with sodium hyaluronate (Mw 100 kDa-200 kDa) of equal weight, and the rest are the same.

[0070] The PDRN non-cross-linked sodium hyaluronate gels obtained in Comparative Examples 1 to 8 were respectively recorded as gel d1 to gel d8.

[0071] Effect evaluation 1. Characterization of small cross-linked structures formed by sodium hyaluronate, zinc chloride, phytic acid and PDRN.

[0072] The solution 3 obtained in step S3 of Example 1 to Example 5 and Comparative Example 1 to Comparative Example 7 was diluted with water under stirring with a glass rod, and gradually diluted to 100 times the original volume. An appropriate amount of the diluted solution was taken and its average particle size was detected using a DLS particle size analyzer. The results are shown in Table 4: Table 4

[0073] It can be seen that in Examples 1 to 5 of the present invention, sodium hyaluronate with a molecular weight of <10kDa can form a submicron particle solution with PDRN, phytic acid, and zinc chloride. In Comparative Example 1, the amount of sodium hyaluronate used is too large, which interferes with the formation of a stable small cross-linked body. In Comparative Example 2 and Comparative Example 3, calcium chloride and magnesium chloride are used to replace an equal amount of zinc chloride, respectively. Although calcium ions and magnesium ions are divalent metal cations like zinc ions, Comparative Examples 2 and Comparative Examples 3 show that the use of calcium chloride and magnesium chloride cannot achieve the formation of a stable submicron particle solution. Comparative Example 4 omits the use of zinc chloride; Comparative Example 5 omits the use of phytic acid. As can be seen from the results, no submicron particle solution is formed in the solution without the use of zinc chloride or phytic acid, which shows that zinc chloride and phytic acid are essential components for the formation of sodium hyaluronate-PDRN small cross-linked bodies. In Comparative Example 6, Solution 2 and Solution 1 are mixed by direct mixing instead of dripping. Due to the uneven mixing process, the generated sodium hyaluronate-PDRN cross-linked body particles are significantly larger. In Comparative Example 7, sodium hyaluronate with a larger weight-average molecular weight is used for cross-linking with PDRN, phytic acid and zinc chloride. Due to the larger molecular weight of sodium hyaluronate, multiple small cross-linking sites may be generated on a single sodium hyaluronate molecule, thereby forming a network-like structure, which further leads to the sedimentation of the cross-linked body.

[0074] 2. Sustained release effect of Gel 1-Gel 5, Gel d1-Gel d8 First, the nucleic acid content in unit concentration gel 1-gel 5 and gel d1-gel d8 was determined by measuring the absorbance at 260nm. Then 1g of gel 1-gel 5 and gel d1-gel d8 were taken and placed in dialysis bags with a molecular weight cutoff of 5000Da, respectively. The dialysis bags were placed in 100mL of PBS aqueous solution with a pH of 7.4 and the stirring speed was 350rpm. 1mL of buffer solution outside the dialysis bag was taken at different times, and the absorbance at 260nm was measured to determine the nucleic acid concentration and total amount of nucleic acid outside the dialysis bag. After each test, the solution was poured back into the buffer beaker. The percentage of nucleic acid release was calculated.

[0075] Nucleic acid concentration (μg / mL) = A ÷ 0.020.

[0076] Wherein, A is the light absorption peak value at 260nm in a 1cm light path cuvette of the solution, and 0.020 is the light absorption concentration coefficient of DNA.

[0077] The nucleic acid release percentages of each group of gels at 24h, 48h, and 72h measured by the above method are shown in Table 5 (“-” indicates nearly complete release and not detected): Table 5

[0078] It can be seen that gel 1 to gel 5 provided by the present invention can achieve a better sustained release effect of nucleic acid, and the nucleic acid release percentage within 24 hours is only 46.90%-58.10%, and the nucleic acid release percentage within 48 hours is only 62.84%-78.81%. However, gel d1 to gel d8 provided in each comparative example do not have the sustained release effect achieved by each embodiment.

[0079] 3. Storage stability evaluation 300 μL of sterile gel was injected into a 1 mL glass transparent vial and stored at 20°C and 40°C for 1 day, 15 days, 30 days and 60 days respectively. The color, transparency and gel state were visually observed. The results of the storage stability test at 20°C are summarized in Table 6: Table 6

[0080] The results of the storage stability test at 40°C are summarized in Table 7: Table 7

[0081] It can be seen that the sodium hyaluronate-PDRN gel provided by Examples 1 to 5 of the present invention has better storage stability at 20°C and 40°C.

[0082] 4. Biosafety Assessment Evaluation of cytotoxicity on human immortalized keratinocytes HaCaT cells.

[0083] Culture medium: DMEM medium + 10% fetal bovine serum (FBS) + 1% penicillin-streptomycin.

[0084] Culture conditions: 37°C, 5% CO2, and 95% humidity.

[0085] Experimental methods: The revived HaCaT cells were subcultured to the logarithmic growth phase, the cells were digested, resuspended in culture medium, and the cells were counted. After adjusting the cell concentration with culture medium, 10,000 cells / well (containing 0.1 mL of culture medium) were inoculated in a 96-well plate. The culture medium was aspirated 24 hours after colonization, and 0.1 mL of a culture medium mixture containing gels of different concentrations was added to each well and cultured for 24 hours. The culture medium was aspirated, and the activity of the HaCaT cells was detected using the MTT cell viability kit. The group with a gel concentration of 0 μg / mL was used as the benchmark for relative viability to calculate the relative viability of HaCaT cells under other concentrations of gel. The experimental results are shown in Table 8 below (average relative viability, dimensionless quantity, with the average relative viability of cells at each gel concentration of 0 μg / mL as 1): Table 8

[0086] It can be seen that the gels provided in the embodiments and comparative examples showed no significant toxicity to HaCaT cells.

[0087] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A PDRN non-cross-linked sodium hyaluronate gel composition, characterized in that: The composition is as follows by weight: 5-15 parts of sodium hyaluronate 1, 1-3 parts of sodium hyaluronate 2, 1-2.7 parts of PDRN, 0.05-0.15 parts of phytic acid, 0.025-0.075 parts of zinc chloride and 200-300 parts of water; Among them, the molecular weight of sodium hyaluronate 1 is 1000kDa-2000kDa; the molecular weight of sodium hyaluronate 2 is less than 10kDa.

2. The PDRN non-crosslinked sodium hyaluronate gel composition according to claim 1, characterized in that The composition is as follows by weight: 8-12 parts of sodium hyaluronate 1, 1.5-2.5 parts of sodium hyaluronate 2, 1.4-2.3 parts of PDRN, 0.08-0.12 parts of phytic acid, 0.04-0.06 parts of zinc chloride and 200-250 parts of water.

3. The PDRN non-crosslinked sodium hyaluronate gel composition according to claim 2, characterized in that The composition is as follows by weight: 10 parts of sodium hyaluronate 1, 2 parts of sodium hyaluronate 2, 1.85 parts of PDRN, 0.1 parts of phytic acid, 0.05 parts of zinc chloride and 236 parts of water.

4. The PDRN non-crosslinked sodium hyaluronate gel composition according to claim 1, characterized in that The molecular weight of the sodium hyaluronate 1 is 1500 kDa±1 kDa.

5. A method for preparing a PDRN non-crosslinked sodium hyaluronate gel using the PDRN non-crosslinked sodium hyaluronate gel composition according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1. Mix the formulated amount of sodium hyaluronate 2, PDRN, zinc chloride and water, and stir to obtain solution 1; S2, mixing the formulated amount of phytic acid with water to obtain solution 2; S3, adding solution 2 dropwise to the stirring solution 1 to obtain solution 3; S4. Mix the formulated amount of sodium hyaluronate 1 with the remaining amount of water, then add solution 3 and mix well to obtain PDRN non-cross-linked sodium hyaluronate gel.

6. The method according to claim 5, characterized in that In step S1, the weight of the water is 16-24 times the sum of the weights of sodium hyaluronate 2, PDRN and zinc chloride; in step S2, the weight of the water is 20-40 times the weight of phytic acid.

7. The method according to claim 5, characterized in that In step S1, the stirring speed is 800-1200rpm, and the stirring time is 8-18h; in step S3, the dropping speed is 0.01-0.05mL / min; the stirring speed is 800-1200rpm; in step S4, the mixing is specifically stirred for 24-48h.

8. A PDRN non-cross-linked sodium hyaluronate gel, characterized in that: Made by the method described in any one of claims 5-7.

9. Use of the PDRN non-crosslinked sodium hyaluronate gel composition described in any one of claims 1-4 or the PDRN non-crosslinked sodium hyaluronate gel prepared by the method described in any one of claims 5-7 in the preparation of medicines, medical devices or cosmetics.

10. A medicine, characterized in that: A PDRN non-cross-linked sodium hyaluronate gel composition containing any one of claims 1 to 4 or a PDRN non-cross-linked sodium hyaluronate gel prepared by the method described in any one of claims 5 to 7.

11. A medical device, characterized in that: A PDRN non-cross-linked sodium hyaluronate gel composition containing any one of claims 1 to 4 or a PDRN non-cross-linked sodium hyaluronate gel prepared by the method described in any one of claims 5 to 7.

12. A cosmetic, characterized in that: A PDRN non-cross-linked sodium hyaluronate gel composition containing any one of claims 1 to 4 or a PDRN non-cross-linked sodium hyaluronate gel prepared by the method described in any one of claims 5 to 7.

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