Collagen implant containing polynucleotide as well as preparation method and application of collagen implant
By mixing polynucleotide gel with collagen gel to form a gel-like implant with a specific concentration and ratio, the problem of poor effect of simple collagen filler on deep wrinkles is solved, achieving a high viscosity and good stability anti-wrinkle effect, suitable for facial and neck filling.
Patent Information
- Application Number
- CN202511307588.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-14
- Publication Date
- 2025-12-19
AI Technical Summary
Existing fillers containing pure collagen are not effective in reducing wrinkles in areas with deep wrinkles, and they are also unstable and prone to separation and stratification.
By mixing polynucleotide gel with collagen gel, a collagen implant containing polynucleotides of a specific concentration and ratio is formed. The gel is formed by heating and cooling steps to ensure the stability and viscosity of the implant.
The resulting implant has high viscosity, which can effectively fill facial and neck wrinkles, has a good anti-wrinkle effect, and is not prone to separation and stratification, thus improving biocompatibility and safety of use.
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Figure CN121154928A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of implant agents, in particular to a collagen implant agent containing polynucleotides and a preparation method and application thereof. BACKGROUND
[0002] Collagen is the main component of animal connective tissue, mainly existing in tissues such as skin, bones, muscles, tendons, ligaments and blood vessels of the human body. Collagen has various functions and effects, and can maintain skin elasticity and moisture, promote wound healing, enhance bone and joint health, etc.
[0003] Therefore, in the prior art, the elasticity of the skin is maintained and the anti-wrinkle effect is achieved by injecting a collagen filler into the skin. However, the filler containing only collagen has poor support, and cannot achieve good anti-wrinkle effect for some deep wrinkles. SUMMARY
[0004] The present application provides a collagen implant agent containing polynucleotides and a preparation method and application thereof. The implant agent is in the form of a gel. The implant agent formed by the appropriate ratio of collagen and polynucleotides has high viscosity and can achieve good anti-wrinkle effect. The implant agent has good stability and is not prone to water separation and layering.
[0005] The present application is implemented as follows:
[0006] In a first aspect, the present application provides a collagen implant agent containing polynucleotides. The implant agent is in the form of a gel, which is formed by mixing a polynucleotide gel and a collagen gel. The content of collagen in the implant agent is 25-40 mg / mL, and the content of polynucleotides is 5-20 mg / mL.
[0007] In a second aspect, the present application provides a preparation method of the collagen implant agent containing polynucleotides according to the first aspect, comprising the following steps:
[0008] Mixing polynucleotides and a phosphate buffer and heating to form a polynucleotide solution; cooling the polynucleotide solution to room temperature to form a polynucleotide gel;
[0009] Mixing the collagen gel and the polynucleotide gel to obtain the collagen implant agent containing polynucleotides.
[0010] In a third aspect, the present application provides an application of the collagen implant agent containing polynucleotides according to the first aspect in preparing facial filling materials and neck filling materials.
[0011] The present application has at least the following beneficial effects:
[0012] The present application describes a collagen implant containing polynucleotides and its preparation method. The implant is formed by mixing a polynucleotide gel and a collagen gel. The collagen content in the implant is 25–40 mg / mL, and the polynucleotide content is 5–20 mg / mL. This ratio and concentration of collagen gel and polynucleotide gel results in an implant with high viscosity, making it a non-flowing but injectable gel, thus providing excellent filling and anti-wrinkle effects. It can be used for facial filling, neck filling, or periocular filling. Furthermore, the implant of this application exhibits good stability and is not prone to water separation or delamination. Attached Figure Description
[0013] Figure 1 Photographs of the collagen implants containing polynucleotides in Examples 1, 2, 1, and 2 of this application;
[0014] Figure 2 A photograph of the polynucleotide gel of Comparative Example 3 of this application;
[0015] Figure 3 This is the state of the collagen implant containing polynucleotides from Example 2 and Comparative Example 1 after being placed for 5 days and then extruded. Detailed Implementation
[0016] The embodiments of this application will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.
[0017] The following provides a detailed description of the collagen implant containing polynucleotides, its preparation method, and its application, based on embodiments of this application:
[0018] In a first aspect, embodiments of this application provide a collagen implant containing polynucleotides. The implant is in the form of a gel, which is formed by mixing polynucleotide gel and collagen gel. The collagen content in the implant is 25-40 mg / mL, and the polynucleotide content is 5-20 mg / mL.
[0019] The collagen implant containing polynucleotide of the embodiments of the present application is formed by mixing the polynucleotide gel and the collagen gel, wherein the content of the collagen in the implant is 25-40 mg / mL, and the content of the polynucleotide (PN for short) is 5-20 mg / mL. The implant formed by the collagen gel and the polynucleotide gel with the above-mentioned ratio and concentration has a high viscosity, so that the implant is in a gel state which is not very flowable but can be injected, thereby being able to play a good filling role and having a good anti-wrinkle effect. It should be noted that in some embodiments, in addition to the polynucleotide gel and the collagen gel, other substances such as sodium hyaluronate can also be added to the collagen implant containing polynucleotide.
[0020] Exemplarily, the pushing force of the implant is 7-18 N, for example, any one of 7 N, 8 N, 9 N, 10 N, 11 N, 12 N, 13 N, 14 N, 15 N, 16 N, 17 N and 18 N or a value between any two of them. The collagen implant containing polynucleotide of the present application can be easily pushed out with a 26G needle, and the whole injection process is not jammed.
[0021] Exemplarily, the molecular weight of the polynucleotide is 2000-10000 KDa. The present inventors have found in research that the polynucleotide gel with a concentration of 10 mg / mL formed by the polynucleotide with the above-mentioned molecular weight has good flowability and can flow by itself after being pushed out of the needle on a flat plate. For example, the molecular weight of the polynucleotide is any one of 2000 KDa, 3000 KDa, 4000 KDa, 5000 KDa, 6000 KDa, 7000 KDa, 8000 KDa, 9000 KDa and 10000 KDa or a value between any two of them.
[0022] Exemplarily, the content of the collagen in the implant is any one of 25 mg / mL, 28 mg / mL, 30 mg / mL, 32 mg / mL, 34 mg / mL, 35 mg / mL, 36 mg / mL, 38 mg / mL and 40 mg / mL or a value between any two of them.
[0023] Exemplarily, the content of the polynucleotide in the implant is any one of 5 mg / mL, 6 mg / mL, 8 mg / mL, 10 mg / mL, 12 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 18 mg / mL and 20 mg / mL or a value between any two of them. The present inventors have found in research that if the content of the polynucleotide in the implant is too low, the implant is prone to water separation. However, in the embodiments of the present application, the content of the polynucleotide in the implant does not cause the implant to separate water.
[0024] In one possible implementation, the collagen content in the implant is 30-40 mg / mL, and the polynucleotide content is 10-20 mg / mL.
[0025] Illustratively, the dynamic viscosity of the implant is 100000-500000 cp, for example, any one of 100000 cp, 200000 cp, 300000 cp, 400000 cp, and 500000 cp or a value between any two of them.
[0026] In the research, the inventors of the present application found that when a polynucleotide gel is mixed with a collagen solution, for example, a polynucleotide solution with a concentration of 20 mg / mL is mixed with a collagen solution with a concentration of 7 mg / mL at a volume ratio of 1:1 to obtain an implant, the collagen content in the implant is 3.5 mg / mL, and the polynucleotide content in the implant is 10 mg / mL. The implant is a transparent gel with low viscosity and cannot play a good filling and supporting role.
[0027] In addition, the molecular weight of the polynucleotide is 2000-10000 KDa. In the research, the inventors of the present application found that the polynucleotide with a molecular weight of 10 mg / mL has good flowability, and can flow by itself after being pushed out of the needle and placed on a flat plate. For example, the molecular weight of the polynucleotide is any one of 2000 KDa, 3000 KDa, 4000 KDa, 5000 KDa, 6000 KDa, 7000 KDa, 8000 KDa, 9000 KDa, and 10000 KDa or a value between any two of them.
[0028] Further, the polynucleotide gel and the collagen gel both contain a phosphate buffer. In the research, the inventors of the present application found that the collagen gel containing the phosphate buffer is white or milky white, and the implant obtained by compounding the polynucleotide gel with the collagen gel is also white or milky white. The white or milky white implant implanted into facial wrinkles, neck wrinkles, or around the eyes can not only play a good filling and supporting role, but also play a role in brightening skin color and covering dark circles.
[0029] In a second aspect, the present application provides a preparation method of the above-mentioned collagen implant containing polynucleotides, which comprises the following steps:
[0030] (1) mixing the polynucleotide with the phosphate buffer and heating to form a polynucleotide solution; cooling the polynucleotide solution to room temperature to form a polynucleotide gel.
[0031] The polynucleotide cannot be dissolved by directly mixing with the phosphate buffer solution, and the two are directly mixed without heating to form a layered structure. When heated, a solution is formed. After the polynucleotide solution is cooled to room temperature, a polynucleotide gel is formed. Illustratively, the heating temperature is 60-90°C, for example, any one of 60°C, 70°C, 80°C and 90°C or a value between any two of them.
[0032] (2) The collagen gel is mixed with the polynucleotide gel to obtain a collagen implant containing polynucleotides.
[0033] The collagen gel is formed by self-assembly of collagen, without adding any chemical or physical cross-linking agent, thereby improving the biocompatibility of the implant. Illustratively, the collagen is animal-derived collagen.
[0034] In a third aspect, the present application provides a use of the above-mentioned collagen implant containing polynucleotides in the preparation of a facial filling material or a neck filling material.
[0035] The collagen implant containing polynucleotides of the present application has high viscosity and can play a good filling role, has good anti-wrinkle effect, and can be used for facial filling and neck filling.
[0036] The collagen implant containing polynucleotides of the present application, the preparation method and the use thereof are further described in detail below in combination with examples.
[0037] Example 1
[0038] The present example provides a collagen implant containing polynucleotides, which is formed by mixing a polynucleotide gel and a collagen gel. The collagen content in the implant is 34 mg / mL, and the polynucleotide content is 10 mg / mL. The molecular weight of the polynucleotide is ≥2000 KDa.
[0039] The preparation steps of the collagen implant containing polynucleotides of the present example include:
[0040] The polynucleotide is mixed with the phosphate buffer solution and heated at a temperature of 70°C to form a polynucleotide solution; the polynucleotide solution is cooled to room temperature to form a polynucleotide gel;
[0041] The collagen gel containing the phosphate buffer solution is mixed with the polynucleotide gel, homogenized and defoamed to obtain a collagen implant containing polynucleotides.
[0042] Example 2
[0043] This embodiment provides a collagen implant containing polynucleotides, which differs from Embodiment 1 only in that the polynucleotide content in the implant is 20 mg / mL.
[0044] Example 3
[0045] This embodiment provides a collagen implant containing polynucleotides, which differs from Embodiment 1 only in that the polynucleotide content in the implant is 5 mg / mL.
[0046] Example 4
[0047] This embodiment provides a collagen implant containing polynucleotides, which differs from Embodiment 1 only in that the collagen content in the implant is 30 mg / mL.
[0048] Comparative Example 1
[0049] Comparative Example 1 provides a collagen implant containing polynucleotides, which differs from Example 1 only in that the polynucleotide content in the implant is 1 mg / mL.
[0050] Comparative Example 2
[0051] Comparative Example 2 provides a collagen implant containing polynucleotides, which differs from Example 1 only in that the collagen implant containing polynucleotides in this example is composed of a mixture of polynucleotide gel and collagen solution, and the collagen content in the implant is 3.5 mg / mL.
[0052] Comparative Example 3
[0053] Comparative Example 3 provides a polynucleotide gel, the preparation steps of which include: mixing polynucleotides with phosphate buffer and heating at 70°C to form a polynucleotide solution; cooling the polynucleotide solution to room temperature to form a polynucleotide gel. The polynucleotide raw materials in Comparative Example 3 are the same as those in Example 1.
[0054] Comparative Example 4
[0055] Comparative Example 4 provides a collagen gel that is identical to the collagen gel in Example 1.
[0056] Experimental Example 1
[0057] The collagen implants containing polynucleotides from Examples 1, 2, Comparative Examples 1 and 2, and the polynucleotide gel from Comparative Example 3 were filled into syringes, and 26G needles were attached. After removing a small amount of air from the tip of the needle, the samples were extruded. Figure 1 , Figure 2 As shown.
[0058] As shown in Figure 1 Figure 1 The photos of the polynucleotide-containing collagen implant of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 are shown. Among them, the polynucleotide-containing collagen implant of Example 1, Example 2, and Comparative Example 1 is a milky white gel, and the polynucleotide-containing collagen implant of Comparative Example 1 has slight water separation after being pushed out. The polynucleotide-containing collagen implant of Comparative Example 2 is transparent and does not flow by itself after being pushed on the plate. Figure 2 The polynucleotide gel of Comparative Example 3 is transparent and has a certain flowability, and slowly flows by itself after being pushed on the plate.
[0059] Test Example 2
[0060] The polynucleotide-containing collagen implants of Example 1, Example 2, Comparative Example 1, and Comparative Example 2 filled in the syringe were placed for 5 days, and then they were pushed out for observation. Among them, the polynucleotide-containing collagen implants of Example 1 and Example 2 are relatively uniform samples after being pushed out; and the polynucleotide-containing collagen implants of Comparative Example 1 and Comparative Example 2 both have obvious water separation and stratification, and the water is obviously pushed out first at the beginning, and the implant sample is pushed out after a period of time. Figure 3 The state of the polynucleotide-containing collagen implants of Example 2 and Comparative Example 1 after being placed and then pushed out is shown.
[0061] It is illustrated that the polynucleotide-containing collagen implant of the embodiment of the present application has better stability, is not easy to separate water and stratify after being placed for a period of time, and is safer to use.
[0062] Test Example 3
[0063] The polynucleotide-containing collagen implants of Examples 1-4 and Comparative Examples 1-2, and the polynucleotide gel of Comparative Example 3, the collagen gel of Comparative Example 4 were tested for pushing force and dynamic viscosity.
[0064] Pushing force test procedure: the sample was filled in the syringe, a 26G needle was installed, a small amount of air at the front end of the injection needle was excluded, and then it was installed on the universal material testing machine for testing, and the testing speed was 50 mm / min. Among them, the average pushing force of each sample is recorded in Table 1.
[0065] Dynamic viscosity test: the dynamic viscosity of the sample was detected according to the rotary viscometer method in the viscosity determination method in the “People's Republic of China Pharmacopoeia” (2020 edition, volume 4) 0633, and the results are recorded in Table 1.
[0066] Table 1. Pushing force and dynamic viscosity test results
[0067] Average push force / N Kinematic viscosity / cp Example 1 8.06 108268 Example 2 16.01 479205 Example 3 7.24 76461 Example 4 7.91 93632 Comparative Example 1 6.55 54821 Comparative Example 2 3.69 15857 Comparative Example 3 2.72 16957 Comparative Example 4 3.81 ——
[0068] The collagen implant containing polynucleotide of Examples 1 to 4 and Comparative Examples 1 to 2 and the polynucleotide gel of Comparative Example 3, the collagen gel of Comparative Example 4 can be easily pushed out through a 26G needle. In addition, the viscosity of the collagen implant containing polynucleotide of the present application is larger, and the filling support effect is better, which greatly reduces the risk of displacement of the product after implanting into the tissue, and is suitable for filling and repairing moderate to severe gravitational wrinkles, and can be used for facial filling and neck filling.
[0069] The above only describes specific embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.
Claims
1. A collagen implant containing polynucleotides, characterized in that, The implant is in the form of a gel, which is formed by mixing a polynucleotide gel and a collagen gel; the collagen content in the implant is 25-40 mg / mL, and the polynucleotide content is 5-20 mg / mL.
2. The collagen implant containing polynucleotides according to claim 1, characterized in that, The pushing force of the implant is 7-18 N.
3. The collagen implant containing polynucleotides according to claim 1, characterized in that, The molecular weight of the polynucleotide is 2000-10000 kDa.
4. The collagen implant containing polynucleotides according to claim 1, characterized in that, The dynamic viscosity of the implant is 100,000 to 500,000 cp.
5. The collagen implant containing polynucleotides according to claim 1, characterized in that, Both the polynucleotide gel and the collagen gel contain phosphate buffer.
6. The collagen implant containing polynucleotides according to any one of claims 1 to 5, characterized in that, The collagen content in the implant is 30-40 mg / mL, and the content of the polynucleotide is 10-20 mg / mL.
7. A method for preparing a collagen implant containing polynucleotides as described in any one of claims 1 to 6, characterized in that, Includes the following steps: The polynucleotide is mixed with phosphate buffer and then heated to form a polynucleotide solution; The polynucleotide solution is cooled to room temperature to form the polynucleotide gel; The collagen gel and the polynucleotide gel are mixed and homogenized to obtain the collagen implant containing polynucleotides.
8. The method for preparing the collagen implant containing polynucleotides according to claim 7, characterized in that, The heating temperature is 60–90°C.
9. The method for preparing the collagen implant containing polynucleotides according to claim 7, characterized in that, The collagen gel is formed by the self-assembly of collagen; optionally, the collagen is animal-derived collagen.
10. The use of a collagen implant containing polynucleotides as described in any one of claims 1 to 6 in the preparation of facial filler materials, neck filler materials, and periocular filler materials.