Composite water-light for injection and preparation method thereof

Abstract

The embodiment of the invention discloses a composite water-light for injection and a preparation method thereof. The composite water-light for injection is prepared from the following raw materials in parts by weight: 30-60 parts of nano poly-L-lactic acid particles and 10-30 parts of sodium hyaluronate. By screening the components, the provided composite hyaluronic acid hydrogel has the advantages of long duration of water and light, uniform particles, good dispersibility, stronger dispersibility in tissues and good needle passing performance, solves the problems of short effect maintenance period, unobvious improvement effect and the like of the traditional hyaluronic acid hydrogel product, and provides a new choice for the field of medical cosmetology.

Description

Technical Field

[0001] The embodiments of the present invention relate to the field of medical cosmetology technology, and specifically to a composite water light for injection and a preparation method thereof. Background Art

[0002] Aging is a long process. The initial appearance of aging is the growth of wrinkles on our skin, larger pores, and sagging skin. These changes begin at about the age of 25, and superficial aging begins to manifest. As age increases, skin problems will evolve from the initial wrinkles and increased pores to more serious dullness, sagging, poor complexion, and yellow skin color. Water-light needles, as the most advanced skin improvement program, originated from mesotherapy, which was first proposed by French doctor Michael Piester in 1952. The mesoderm is located between the epidermis and the dermis. It is the key part for the skin to absorb the effective ingredients of topical beauty products. It is also the layer with the most fibroblasts. 90% of the fibroblasts in our body are concentrated between the epidermis and dermis and in the dermis. The epidermis is the iron wall of human skin. Most topical beauty cosmetics are difficult to penetrate the epidermis into the deep skin due to molecular structure problems, so the effect is not significant.

[0003] Mesotherapy uses ultra-micro-penetration technology to locate, determine the layers, and quantitatively deliver high-concentration skin nutrients containing a variety of nutrients directly through the epidermis to the deep subcutaneous tissue, which is equivalent to directly providing "nutrients" to the deep skin. The deep skin full of nutrients instantly presents unprecedented luster, clarity, and whitening. This new technology, which is equivalent to "drug administration from the root", can fundamentally solve skin problems such as pigmentation, dull skin tone, acne, yellowing, dullness, fine lines, loose skin, sagging skin, etc.

[0004] Hyaluronic acid injection is a non-surgical cosmetic method that achieves cosmetic effects by injecting skin care ingredients such as hyaluronic acid. The method of hyaluronic acid injection is essentially similar to hyaluronic acid injection, but the location and method of injection are different. It can improve the skin quality and whitening effect of the face at the same time. Compared with other non-surgical cosmetic methods, hyaluronic acid injection has a more significant effect, and the subsequent maintenance is relatively simple. At the same time, there are also obvious disadvantages: after too many hyaluronic acid injections, "tear grooves" and "bird's nest" phenomena will occur, resulting in an uneven or even bumpy surface. In addition, the effect of hyaluronic acid injection beauty usually requires several injections, which means it takes a long time to achieve the best effect. Summary of the invention

[0005] To this end, an embodiment of the present invention provides an injectable composite hyaluronic acid hyaluronic acid injection and a preparation method thereof to solve the defects of the existing hyaluronic acid hyaluronic acid injection, such as short duration and unclear effect.

[0006] In order to achieve the above purpose, the embodiment of the present invention provides the following technical solutions:

[0007] According to a first aspect of an embodiment of the present invention, the present invention provides a composite hyaluronic acid for injection, which is made of the following raw materials in parts by weight: 30-60 parts of nano poly-L-lactic acid microparticles and 10-30 parts of sodium hyaluronate.

[0008] Furthermore, it is made of the following raw materials by weight: 50 parts of nano-poly-L-lactic acid and 10-20 parts of sodium hyaluronate.

[0009] Furthermore, the particle size of the nano poly-L-lactic acid microparticles is 100nm-600nm, preferably 200nm-400nm.

[0010] Furthermore, the molecular weight of the sodium hyaluronate is 200KDa-1800KDa.

[0011] Furthermore, the preparation method of the nano poly-L-lactic acid microparticles is as follows:

[0012] Dissolve poly-L-lactic acid in dichloromethane and stir until completely dissolved; add DDH2O and disperse evenly by ultrasonication; add 5% polyvinyl alcohol aqueous solution and disperse evenly by ultrasonication; add 2% isopropanol and stir at room temperature until dichloromethane is completely volatilized; freeze-dry to obtain the nano poly-L-lactic acid particles, wherein the mass volume ratio of polymerized poly-L-lactic acid, dichloromethane, DDH2O, 5% polyvinyl alcohol aqueous solution and 2% isopropanol is 10:2:0.2:2:4.

[0013] Traditional poly-L-lactic acid raw material particles are relatively large, and when injected into the dermis with a larger dosage, hardening is easily formed, and reducing the dosage has the defect of poor effect. For this reason, the present invention makes poly-L-lactic acid into nano poly-L-lactic acid microparticles according to the above method, which can not only solve the hardening problem of large particles, but also the quantity of single milliliter of poly-L-lactic acid can be improved, and in the dermis tissue, poly-L-lactic acid has better dispersibility, is not easy to form precipitation, and is not easy to accumulate, so that hardening will not be formed in the tissue, and when the dosage is enough, the new collagen and collagen fibers produced are more, so as to improve the early aging skin problems such as enlarged skin pores, more superficial fine lines, and dull skin.

[0014] Furthermore, the molecular weight of the poly-L-lactic acid is 8KDa-12KDa, preferably 10KDa-12KDa.

[0015] According to a second aspect of an embodiment of the present invention, the present invention provides a method for preparing the composite water-light for injection as described in any one of the above items, comprising the following steps:

[0016] (1) dissolving sodium hyaluronate in the first injection water, stirring thoroughly to dissolve, and obtaining a sodium hyaluronate gel solution;

[0017] (2) dissolving the nano-PLA microparticles in the second water for injection, stirring and dissolving the nano-PLA microparticles, and passing the nano-PLA through a 400-mesh sieve to obtain a PLA aqueous solution;

[0018] (3) Mixing the sodium hyaluronate gel solution of step (1) and the poly-L-lactic acid aqueous solution of step (2), stirring evenly, to obtain the composite aqueous solution for injection.

[0019] Furthermore, the amount of the first water for injection is 50-100 times the mass of sodium hyaluronate.

[0020] Furthermore, the dosage of the second water for injection is 5-15 times the mass of the nano-PLA microparticles.

[0021] The embodiments of the present invention have the following advantages:

[0022] Through the screening of components, the composite hyaluronic acid hyaluronic acid hyaluronic acid products provided by the present invention has a long duration, uniform particles, good dispersibility, stronger dispersibility in tissues, and good needle permeability, thus solving the problems of short effect maintenance period and unclear improvement effect of traditional hyaluronic acid hyaluronic acid hyaluronic acid products, and providing a new choice for the field of medical cosmetology. DETAILED DESCRIPTION

[0023] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. 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.

[0024] Example 1

[0025] Screening of compound water light prescription for injection

[0026] 1. Test sample: Prepare the composite water-light for injection according to the following method.

[0027] Preparation method:

[0028] ① Dissolve sodium hyaluronate (molecular weight 1500kda-1800kda) in 1000ml of water for injection, stir thoroughly to dissolve, and set aside;

[0029] ② Dissolve the nano poly-L-lactic acid microspheres in 500 ml of water for injection. After fully dissolved, pass through a 400-mesh sieve;

[0030] ③ Add the solution obtained in step ② to ①, stir evenly with a machine, and then fill it into a vial to obtain the compound aqueous solution for injection, and then divide it into 500 bottles.

[0031] The preparation method of nano poly-L-lactic acid microspheres is as follows:

[0032] 1. Take 10 grams of poly-L-lactic acid and dissolve it in 2L of dichloromethane, stirring continuously until it is completely dissolved, then add 200mL of DDH2O, then ultrasonicate at 47%, ultrasonicate for 5 seconds, air for 5 seconds, and cycle for a total of 2 minutes.

[0033] 2. Add 2L of 5% polyvinyl alcohol aqueous solution (molecular weight 65000-75000), then ultrasonicate 47%, ultrasonicate for 5 seconds, empty for 5 seconds, and cycle for a total of 2 minutes.

[0034] 3. Add 4 L of 2% isopropanol and stir at room temperature for 24 hours until the dichloromethane is completely evaporated.

[0035] 4. Freeze-drying to obtain nano-poly L-lactic acid microparticles.

[0036] The material properties and dosage relationships of each prescription are shown in Table 1.

[0037] Table 1

[0038]

[0039]

[0040] 2. Experimental methods

[0041] The duration, needle permeability and particle size of the compound water for injection of prescriptions 1-18 were tested.

[0042] Duration: Inject the test sample into the body of experimental mice with a syringe. After one week, dissect the experimental mice and use an electron microscope to observe the collagen growth of the tissue section at the injection site to determine the duration.

[0043] Needle passability: Take 3 bottles of homemade test samples, use a syringe with a 34G needle to extract the test samples, and then squeeze them out. Whether the process is smooth or not can be divided into 3 levels. Level 1: Smooth, no blockage; Level 2: Can pass through the 34G needle, and there is resistance when pushing the syringe; Level 3: Completely blocked, the syringe cannot be pushed.

[0044] Particle size in composite gel: tested and observed using an optical microscope.

[0045] The test results are shown in Table 2.

[0046] Table 2

[0047]

[0048]

[0049] Experimental data show that the duration, needle permeability and particle size of prescriptions 6, 8, 11 and 12 are more conducive to clinical use.

[0050] Example 2

[0051] Stability verification of the injection nano-poly-L-lactic acid and sodium hyaluronate composite water light formula

[0052] 1. Test samples: Three batches of prescriptions 6, 8, 11, and 12 in Table 2 were used for prescription stability verification.

[0053] 2. Experimental method: Same as Example 1.

[0054] 3. The experimental results are shown in Table 3. The injectable nano-poly-L-lactic acid and sodium hyaluronate composite water-light prepared from different batches can achieve the effect of long duration and good needle permeability, and the difference between different batches is not large, and the stability is good.

[0055] Table 3

[0056]

[0057]

[0058] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A composite water light for injection, characterized in that: The invention is prepared from the following raw materials in parts by weight: 30-60 parts of nano poly-L-lactic acid microparticles and 10-30 parts of sodium hyaluronate.

2. The composite water light for injection according to claim 1, characterized in that: The invention is made of the following raw materials by weight: 50 parts of nano-poly-L-lactic acid and 10-20 parts of sodium hyaluronate.

3. The composite water light for injection according to claim 1, characterized in that: The particle size of the nano poly-L-lactic acid particles is 100nm-600nm.

4. The composite water light for injection according to claim 1, characterized in that: The molecular weight of the sodium hyaluronate is 200KDa-1800KDa.

5. The composite water light for injection according to claim 1, characterized in that: The preparation method of the nano poly-L-lactic acid microparticles is as follows: Dissolve poly-L-lactic acid in dichloromethane and stir until completely dissolved; add DDH2O and disperse evenly by ultrasonication; add 5% polyvinyl alcohol aqueous solution and disperse evenly by ultrasonication; add 2% isopropanol and stir at room temperature until dichloromethane is completely volatilized; freeze-dry to obtain the nano poly-L-lactic acid particles, wherein the mass volume ratio of polymerized poly-L-lactic acid, dichloromethane, DDH2O, 5% polyvinyl alcohol aqueous solution and 2% isopropanol is 10:2:0.2:2:

4.

6. The composite water light for injection according to claim 5, characterized in that: The molecular weight of the poly-L-lactic acid is 8KDa-12KDa.

7. A method for preparing the composite water-light for injection according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) dissolving sodium hyaluronate in the first injection water, stirring thoroughly to dissolve, and obtaining a sodium hyaluronate gel solution; (2) dissolving the nano-PLA microparticles in the second water for injection, stirring and dissolving the nano-PLA microparticles, and passing the nano-PLA through a 400-mesh sieve to obtain a PLA aqueous solution; (3) Mixing the sodium hyaluronate gel solution of step (1) and the poly-L-lactic acid aqueous solution of step (2), stirring evenly, to obtain the composite aqueous solution for injection.

8. The method for preparing the composite water-light for injection according to claim 7, characterized in that: The dosage of the first water for injection is 50-100 times the mass of sodium hyaluronate.

9. The method for preparing the composite water-light for injection according to claim 7, characterized in that: The dosage of the second water for injection is 5-15 times the mass of the nano-poly-L-lactic acid microparticles.

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