Low-temperature transparent milky-white collagen implant and preparation method thereof

Abstract

The invention discloses a low-temperature transparent milky-white collagen implant and a preparation method thereof. The collagen implant is prepared by compounding a component A and a component B, the component A is a collagen solution; the component B is prepared from the following components: disodium ethylene diamine tetraacetate, trihydroxymethyl aminomethane, mannitol, glucose and water for injection. The preparation method comprises the following steps: S1, preparing a component A: putting collagen and water for injection into a homogenizer, and uniformly mixing and stirring under a vacuum condition to obtain the component A, namely a collagen solution; s2, preparing a component B: uniformly mixing disodium ethylene diamine tetraacetate, trihydroxymethyl aminomethane, mannitol, glucose and water for injection to obtain the component B; s3, mixing: adding the component B into the component A, then putting the mixture into a homogenizer, uniformly mixing and stirring under a vacuum condition, and filtering and canning to obtain the low-temperature transparent milky white collagen implant.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to a collagen implant which is transparent at low temperature and milky white at body temperature and a preparation method thereof. Background Art

[0002] Collagen is the main structural protein of human tissues and organs. It has stable physical and chemical properties and good biological activity. It has the characteristics of promoting cell proliferation and coordinating with new cells and tissues to repair wounds. It has been widely used in wound dressings, hemostatic materials, cosmetic fillings and water-light materials. In the medical beauty scene, injecting collagen products into sunken skin tissue can nourish, hydrate, resist aging, whiten and tighten the skin.

[0003] At present, animal-derived collagen products on the market are all suspensions (such as "Fu Rou Mei" and "Fu Man", etc.), that is, collagen fibers are dispersed in saline or phosphate-buffered saline, and are used for facial dermal tissue filling to correct dynamic wrinkles on the forehead (such as frown lines, forehead lines and crow's feet, etc.). However, in practice, it is found that after long storage time or temperature changes, its uniformity is difficult to guarantee, and the pushing is unstable during injection, and the support effect after filling is insufficient. Summary of the invention

[0004] The purpose of the present invention is to provide a collagen implant that is transparent at low temperature and milky white at body temperature in response to the above-mentioned problems of existing collagen products. When stored at low temperature, the collagen implant is transparent in appearance, has a uniform gel, good stability, and is smoothly injected and pushed. It has a better supporting effect in clinical applications, and its appearance turns into milky white at body temperature, which has the effect of whitening and covering spots.

[0005] To achieve the above object, the present invention is implemented by the following technical solutions:

[0006] The present invention provides a collagen implant which is transparent at low temperature and milky white at body temperature. The collagen implant is compounded by component A and component B;

[0007] Wherein, the component A is a collagen solution;

[0008] The component B comprises the following components: disodium edetate, tris(hydroxymethyl)aminomethane, mannitol, glucose and water for injection.

[0009] Furthermore, a collagen implant which is transparent at low temperature and milky white at body temperature has a pH value of 6.0 to 8.0.

[0010] Furthermore, a collagen implant which is transparent at low temperature and milky white at body temperature: the weight ratio of component A to component B is 1:(0.3-0.9).

[0011] Furthermore, a collagen implant which is transparent at low temperature and milky white at body temperature: the component A is a collagen solution with a pH value of 2.0 to 3.0.

[0012] Furthermore, a collagen implant which is transparent at low temperature and milky white at body temperature: the content of collagen in the collagen solution is 2.0 to 9.0 wt%.

[0013] Furthermore, a collagen implant which is transparent at low temperature and milky white at body temperature is provided: the component B comprises the following components in mass fractions: 0.1-0.7wt% of disodium ethylenediaminetetraacetate, 0.2-1.0wt% of tris(hydroxymethyl)aminomethane, 2.0-5.0wt% of mannitol, 1.0-2.0wt% of glucose and the balance of water for injection.

[0014] The present invention also provides a method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature, the method comprising the following steps:

[0015] S1. preparing component A: placing collagen and water for injection in a homogenizer and mixing them evenly under vacuum conditions to obtain component A, i.e., collagen solution;

[0016] S2. preparing component B: uniformly mixing disodium edetate, tris(hydroxymethylaminomethane), mannitol, glucose and water for injection to obtain component B;

[0017] S3, mixing: adding the component B to the component A, and then placing in a homogenizer and mixing and stirring evenly under vacuum conditions, filtering, and canning to obtain a collagen implant that is transparent at low temperature and milky white at body temperature.

[0018] Furthermore, a method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature is provided: in step S1, the revolution speed of the homogenizer is 100 to 800 rpm, the rotation speed is 100 to 800 rpm, the vacuum degree is -100 to -80 KPa, and the stirring time is 5 to 15 minutes.

[0019] Furthermore, a method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature: the revolution speed of the homogenizer in step S3 is 300-700 rpm, the rotation speed is 200-600 rpm, the vacuum degree is -100--80 KPa, and the stirring time is 3-20 minutes.

[0020] Furthermore, a method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature: the pore size of the filter element used for filtration in step S3 is 40 to 120 μm.

[0021] Beneficial effects of the present invention:

[0022] (1) The collagen implant provided by the present invention can be transparent when stored at low temperature, and can turn into milky white at body temperature, which has the effect of whitening and concealing spots. Specifically, the existing collagen products will precipitate white fibers under neutral conditions, while the present invention can inhibit the formation of collagen fibers under room temperature / low temperature conditions by optimizing the ingredients and utilizing the combined effects of added components such as disodium ethylenediaminetetraacetic acid, tris(hydroxymethyl)aminomethane, mannitol, and glucose, so that the collagen implant of the present invention will not precipitate collagen even under neutral conditions and will be transparent. When the temperature is raised to body temperature of 37°C, the collagen can self-assemble to form milky white fibers.

[0023] (2) The biggest difference between the collagen implant provided by the present invention and the products on the market is that it is not a suspension, but a uniform gel, which has good stability, smooth injection and pushing, and better support effect in clinical application. The collagen implant of the present invention can inhibit the formation of collagen fibers by adding the composition, improve the performance of collagen gel by adding mannitol as a water-excipient, and provide nutrients for cells after tissue filling by adding glucose.

[0024] (3) The high-speed vacuum homogenization technology is used in the preparation process of the collagen implant of the present invention, which ensures the uniformity and stability of the high-concentration collagen gel mixing. At the same time, the filtration step is combined in the process, so that the obtained collagen implant can be pushed and stabilized during injection. The preparation process of the present invention is simple in preparation process, short in cycle, and has broad market prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 This is a product state diagram of the collagen implant prepared in Example 1 of the present invention under low temperature (2-8°C) and body temperature (37°C);

[0027] Figure 2 This is a product state diagram of the collagen implant prepared in Example 2 of the present invention under low temperature (2-8°C) and body temperature (37°C);

[0028] Figure 3 This is a product state diagram of the collagen implant prepared in Example 3 of the present invention under low temperature (2-8°C) and body temperature (37°C) conditions. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example 1

[0031] This embodiment 1 provides a collagen implant that is transparent at low temperature and milky white at body temperature, wherein the collagen implant is compounded by component A and component B in a weight ratio of 1:0.43;

[0032] Wherein, the component A adopts a collagen solution with a pH value of 2.5, and the collagen solution contains 5.0wt% collagen and 95.0wt% water for injection;

[0033] Wherein, the component B comprises the following components: 0.6wt% of disodium ethylenediaminetetraacetate, 0.84wt% of tris(hydroxymethyl)aminomethane, 5.0wt% of mannitol, 1.4wt% of glucose and the remainder of water for injection.

[0034] The method for preparing the collagen implant which is transparent at low temperature and milky white at body temperature of the above-mentioned embodiment 1 comprises the following specific steps:

[0035] S1. Prepare component A: place 5.0wt% collagen and 95.0wt% water for injection in a homogenizer and mix and stir evenly under vacuum conditions to obtain component A, i.e., a collagen solution; in step S1, the revolution speed of the homogenizer is 500rpm, the rotation speed is 500rpm, the vacuum degree is -90KPa, and the homogenization stirring time is 13 minutes;

[0036] S2. preparing component B: uniformly mixing 0.6 wt % of disodium ethylenediaminetetraacetate, 0.84 wt % of tris(hydroxymethyl)aminomethane, 5.0 wt % of mannitol, 1.4 wt % of glucose and the remainder of water for injection to obtain component B;

[0037] S3, mixing: adding the above-mentioned component B to component A (collagen solution) at a weight ratio of 0.43:1, and then placing in a homogenizer and mixing and stirring evenly under vacuum conditions, filtering, and canning to obtain a collagen implant that is transparent at low temperature and milky white at body temperature;

[0038] In step S3, the revolution speed of the homogenizer is 500 rpm, the rotation speed is 400 rpm, the vacuum degree is -90 KPa, the stirring time is 10 minutes, and the pore size of the filter element used for filtration is 50 μm.

[0039] Example 2

[0040] This embodiment 2 provides a collagen implant that is transparent at low temperature and milky white at body temperature, wherein the collagen implant is compounded by component A and component B in a weight ratio of 1:0.78;

[0041] Wherein, the component A adopts a collagen solution with a pH value of 2.2, and the collagen solution contains 8.0wt% collagen and 92.0wt% water for injection;

[0042] Wherein, the component B comprises the following components: 0.19wt% of disodium ethylenediaminetetraacetate, 0.27wt% of tris(hydroxymethyl)aminomethane, 3.5wt% of mannitol, 1.8wt% of glucose and the remainder of water for injection.

[0043] The method for preparing the collagen implant which is transparent at low temperature and milky white at body temperature of the above-mentioned embodiment 2 comprises the following specific steps:

[0044] S1. Prepare component A: put 8.0wt% collagen and 92.0wt% water for injection in a homogenizer and mix and stir them evenly under vacuum to obtain component A, i.e., collagen solution; in step S1, the revolution speed of the homogenizer is 750rpm, the rotation speed is 750rpm, the vacuum degree is -95KPa, and the homogenization stirring time is 8 minutes;

[0045] S2. preparing component B: uniformly mixing 0.19 wt % of disodium ethylenediaminetetraacetate, 0.27 wt % of tris(hydroxymethyl)aminomethane, 3.5 wt % of mannitol, 1.8 wt % of glucose and the remainder of water for injection to obtain component B;

[0046] S3, mixing: adding the above-mentioned component B to component A (collagen solution) at a weight ratio of 0.78:1, and then placing in a homogenizer and mixing and stirring evenly under vacuum conditions, filtering, and canning to obtain a collagen implant that is transparent at low temperature and milky white at body temperature;

[0047] In step S3, the revolution speed of the homogenizer is 650 rpm, the rotation speed is 550 rpm, the vacuum degree is -95 KPa, the stirring time is 18 minutes, and the pore size of the filter element used for filtration is 70 μm.

[0048] Example 3

[0049] This embodiment 3 provides a collagen implant that is transparent at low temperature and milky white at body temperature, wherein the collagen implant is compounded by component A and component B in a weight ratio of 1:0.6;

[0050] Wherein, the component A adopts a collagen solution with a pH value of 2.8, and the collagen solution contains 4.0wt% collagen and 96.0wt% water for injection;

[0051] Wherein, the component B comprises the following components: 0.7wt% of disodium ethylenediaminetetraacetate, 1.0wt% of tris(hydroxymethyl)aminomethane, 2.1wt% of mannitol, 1.6wt% of glucose and the remainder of water for injection.

[0052] The method for preparing the collagen implant which is transparent at low temperature and milky white at body temperature of the above-mentioned embodiment 3 comprises the following specific steps:

[0053] S1. Prepare component A: put 4.0wt% collagen and 96.0wt% water for injection in a homogenizer and mix and stir them evenly under vacuum to obtain component A, i.e., collagen solution; in step S1, the revolution speed of the homogenizer is 250rpm, the rotation speed is 350rpm, the vacuum degree is -85KPa, and the homogenization stirring time is 15 minutes;

[0054] S2. preparing component B: uniformly mixing 0.7 wt % of disodium ethylenediaminetetraacetate, 1.0 wt % of tris(hydroxymethyl)aminomethane, 2.1 wt % of mannitol, 1.6 wt % of glucose and the remainder of water for injection to obtain component B;

[0055] S3, mixing: adding the above-mentioned component B to component A (collagen solution) at a weight ratio of 0.6:1, and then placing in a homogenizer and mixing and stirring evenly under vacuum conditions, filtering, and canning to obtain a collagen implant that is transparent at low temperature and milky white at body temperature;

[0056] In step S3, the revolution speed of the homogenizer is 350 rpm, the rotation speed is 300 rpm, the vacuum degree is -85 KPa, the stirring time is 8 minutes, and the pore size of the filter element used for filtration is 100 μm.

[0057] The appearance of the collagen implants prepared in Examples 1 to 3 at low temperature (2 to 8°C) and body temperature (37°C) are as follows: Figures 1 to 3 shown by Figures 1 to 3 It can be seen that the collagen implants prepared in Examples 1 to 3 are transparent at low temperatures of 2 to 8°C and are milky white at 37°C.

[0058] In summary, the collagen implant provided by the present invention, which is transparent at low temperature and milky white at body temperature, is transparent in appearance, has uniform gel, good stability, smooth injection and pushing, and strong support when stored at low temperature; its appearance turns into milky white at body temperature, and can have the effect of whitening and covering spots; the method for preparing the collagen implant of the present invention has a simple preparation process and a short cycle.

[0059] The above are preferred embodiments of the present invention and are only used to explain the present invention, not to limit the present invention. Any obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A collagen implant which is transparent at low temperature and milky white at body temperature, characterized in that: The collagen implant is compounded by component A and component B; Wherein, the component A is a collagen solution; The component B comprises the following components: disodium edetate, tris(hydroxymethyl)aminomethane, mannitol, glucose and water for injection.

2. The collagen implant that is transparent at low temperature and milky white at body temperature according to claim 1, characterized in that: The pH value of the collagen implant is 6.0-8.

0.

3. A collagen implant that is transparent at low temperature and milky white at body temperature according to claim 1 or 2, characterized in that: The weight ratio of component A to component B is 1:(0.3-0.9).

4. The collagen implant that is transparent at low temperature and milky white at body temperature according to claim 1 or 2, characterized in that: The component A is a collagen solution with a pH value of 2.0 to 3.

0.

5. A collagen implant that is transparent at low temperature and milky white at body temperature according to any one of claims 1 to 4, characterized in that: The content of collagen in the collagen solution is 2.0-9.0 wt %.

6. The collagen implant that is transparent at low temperature and milky white at body temperature according to claim 1 or 2, characterized in that: The component B comprises the following components in mass fractions: 0.1-0.7 wt% of disodium ethylenediaminetetraacetate, 0.2-1.0 wt% of tris(hydroxymethyl)aminomethane, 2.0-5.0 wt% of mannitol, 1.0-2.0 wt% of glucose and the remainder of water for injection.

7. A method for preparing a collagen implant that is transparent at low temperature and milky at body temperature according to any one of claims 1 to 6, characterized in that: The method comprises the following steps: S1. preparing component A: placing collagen and water for injection in a homogenizer and mixing them evenly under vacuum conditions to obtain component A, i.e., collagen solution; S2. preparing component B: uniformly mixing disodium edetate, tris(hydroxymethyl)aminomethane, mannitol, glucose and water for injection to obtain component B; S3, mixing: adding the component B to the component A, and then placing in a homogenizer and mixing and stirring evenly under vacuum conditions, filtering, and canning to obtain a collagen implant that is transparent at low temperature and milky white at body temperature.

8. The method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature according to claim 7, characterized in that: In step S1, the revolution speed of the homogenizer is 100 to 800 rpm, the rotation speed is 100 to 800 rpm, the vacuum degree is -100 to -80 KPa, and the stirring time is 5 to 15 minutes.

9. The method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature according to claim 7, characterized in that: In step S3, the revolution speed of the homogenizer is 300 to 700 rpm, the rotation speed is 200 to 600 rpm, the vacuum degree is -100 to -80 KPa, and the stirring time is 3 to 20 minutes.

10. The method for preparing a collagen implant that is transparent at low temperature and milky white at body temperature according to claim 7, characterized in that: The pore size of the filter element used for filtration in step S3 is 40 to 120 μm.

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