Composition containing lactic acid, injection containing composition as well as preparation method and application of injection

Abstract

The invention discloses a composition containing lactic acid, an injection containing the composition as well as a preparation method and application of the composition, the composition provided by the invention comprises an amphiphilic polymer and lactic acid, the elasticity and compactness of skin can be remarkably improved, the effect of the composition is better than that of the amphiphilic polymer or lactic acid which is independently used, and a certain synergistic effect is achieved. The composition not only solves the limitation of existing materials, has excellent biocompatibility, injection performance and other multifunctionality so as to meet the diversified requirements of modern skin care, but also can directly reach the deep layer of skin due to the excellent moisturizing performance and collagen regeneration promoting capacity, so that the skin care effect is good, and the skin care effect is good. And a long-term and lasting effect is provided for improving the skin appearance and maintaining the health state of the skin.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer materials and medical cosmetology, and more specifically to a composition containing lactic acid, an injection containing the composition, and a preparation method and application thereof. Background Art

[0002] As the global population structure changes, skin health issues are increasingly receiving widespread attention. Skin conditions are not only related to personal image, but may also affect overall health; for example, dry skin, lack of elasticity, increased fine lines and other problems. Therefore, it is particularly important to develop high-performance medical beauty products, especially those that can deeply moisturize, promote collagen production and enhance skin elasticity. These products can not only improve the appearance of the skin, but also maintain the health of the skin, meeting the modern people's pursuit of a better life.

[0003] In the existing technology, hyaluronic acid, as a well-known moisturizing ingredient, is widely used in cosmetics and beauty projects such as hyaluronic acid injections. However, its ability to repair deep skin tissue and promote collagen regeneration is limited and it can only last for a short time in the body, which limits its comprehensive application in the field of medical beauty.

[0004] In addition, with the advancement of science and technology, the requirements for biomedical materials are no longer limited to a single function, but are developing in the direction of multi-function and intelligent response. For example, an ideal water light needle material preparation should be able to maintain a good moisturizing effect while having multiple functions such as promoting skin cell metabolism, enhancing skin elasticity, and resisting external environmental damage. However, most products on the market currently find it difficult to meet these requirements at the same time.

[0005] In view of the above background, it is necessary not only to overcome the limitations of existing materials, but also to adapt to the diversified needs of modern skin care. How to develop a product with excellent biocompatibility, injection performance and functions has become an urgent problem to be solved by technical personnel in this field. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a lactic acid-containing composition, an injection containing the composition, and a preparation method and application thereof, which not only solve the limitations of existing materials and have excellent biocompatibility, injection performance and other multifunctionality to adapt to the diversified needs of modern skin care, but also the composition designed by the present invention has excellent moisturizing properties and collagen regeneration promoting ability to reach deep into the skin, providing a long-lasting effect in improving skin appearance and maintaining skin health.

[0007] In order to achieve the above-mentioned object, one of the objects of the present invention is to provide a composition containing lactic acid; comprising: an amphiphilic polymer and lactic acid;

[0008] Wherein, the mass ratio of the amphiphilic polymer to the lactic acid is (2-40) g:(0.01-2) g.

[0009] It can be seen from the above technical solution that compared with the prior art, the present invention discovers for the first time that the combination of amphiphilic polymers and lactic acid can significantly improve skin elasticity and firmness, and the effect is better than the use of amphiphilic polymers or lactic acid alone, and has a certain synergistic effect. Therefore, amphiphilic polymers and lactic acid have significant advantages, especially in promoting skin collagen regeneration.

[0010] Preferably, the amphiphilic polymer is a polyether A-polyester B block copolymer, including an ABA or B AB type triblock copolymer, an AB type diblock copolymer, an AgB or BgA type graft copolymer.

[0011] Preferably, the polyether A block is polyethylene glycol with a molecular weight of 200-5000, and the polyester B block is an aliphatic polyester with a molecular weight of 200-5000.

[0012] Preferably, the polyester B block comprises at least one of the following lactide copolymers: poly D,L-lactide, poly D-lactide or poly L-lactide; and further comprises: one or more of polyglycolide, poly ε-caprolactone, poly δ-valerolactone, polycarbonate, polyamide or polyether ester.

[0013] Preferably, the lactic acid comprises one or a mixture of D-lactic acid, L-lactic acid, D,L-lactic acid.

[0014] The second purpose of the present invention is to use the above composition in skin care products and medical beauty products; the product is preferably an injection solution for improving skin elasticity and firmness, and more preferably an injection solution for promoting skin collagen regeneration.

[0015] The third object of the present invention is to provide an injection solution, characterized in that it comprises the above-mentioned lactic acid-containing composition.

[0016] Preferably, the injection solution is in liquid state under low temperature conditions and can quickly turn into a gel state when the temperature rises to the normal temperature of the human body.

[0017] Furthermore, the injection has a thermo-induced gelling property, presenting an injectable solution state at low temperature, transforming into a physical gel at high temperature, and precipitating at excessively high temperature; that is, the solution-gel phase transition temperature of the injection is 4-50°C, and the gel-precipitation phase transition temperature is 30-80°C.

[0018] As can be seen from the above, the present invention combines amphiphilic polymers and lactic acid in a certain ratio as an injection solution to better achieve tissue collagen regeneration. At the same time, the present invention finds that the combination of amphiphilic polymers and lactic acid can better release lactic acid throughout the whole cycle to stimulate tissue collagen regeneration. The lactic acid released in the early stage mainly comes from the lactic acid wrapped by the amphiphilic polymer, and in the later stage it mainly comes from the lactic acid slowly released during the degradation process of the polymer itself, and the wrapped lactic acid will be mostly released in the early stage of polymer degradation. The present invention utilizes the temperature-sensitive properties of the polymer and organically combines with lactic acid to achieve the above-mentioned unexpected technical effects.

[0019] Preferably, the mass fraction of the amphiphilic polymer in the injection is 2wt%-40wt%; the mass fraction of the lactic acid in the injection is 0.01wt% to 2wt%.

[0020] Preferably, the injection solution further comprises: a combination of one or more of an isotonic agent, a pH regulator, an analgesic, a whitening factor, a moisturizing factor, an anti-wrinkle factor, and an antioxidant factor;

[0021] The isotonic agent includes one or more of sodium chloride, glycerol, glucose, and phosphate;

[0022] The pH regulator includes one or more of calcium carbonate, sodium carbonate, and sodium bicarbonate;

[0023] The analgesic comprises one or more of diclofenac sodium, lidocaine, flurbiprofen axetil, parecoxib sodium, ketorolac tromethamine, and celecoxib;

[0024] The whitening factor includes one or more of salicylic acid, vitamin C, glycoside, asiatica glycoside, arbutin, kojic acid, and niacinamide;

[0025] The moisturizing factor includes one or more of glycerin, urea, and hyaluronic acid;

[0026] The anti-wrinkle factor comprises gelatin and / or collagen;

[0027] The antioxidant factors include vitamin E and / or tea polyphenols.

[0028] A fourth object of the present invention is to provide a method for preparing an injection, which specifically comprises using the above-mentioned lactic acid-containing composition as an effective ingredient or the above-mentioned injection to prepare it.

[0029] Preferably, the amphiphilic polymer is first dissolved in a suitable amount of solvent to form a polymer solution, and then lactic acid is dissolved in the obtained polymer solution to form an injection solution.

[0030] Furthermore, the biodegradation period of the injection is 1-8 weeks, including the release of lactic acid in the initial stage of degradation and the release of lactic acid and its derivatives produced by the degradation of the amphiphilic polymer in the middle and late stages of degradation.

[0031] Specifically, the injection can be biodegraded in the body after injection. In the early stage of degradation, the main component released comes from the lactic acid pre-contained in the injection; in the middle and late stages of degradation, the main source is converted to lactic acid and its derivatives produced by the gradual degradation of amphiphilic polymers. The lactic acid and its derivatives can effectively stimulate the production of collagen in skin tissue, thereby significantly improving the elasticity and firmness of the skin.

[0032] Furthermore, the injection is used to improve skin elasticity and firmness and promote skin collagen production.

[0033] Furthermore, the lactic acid and its derivatives include lactic acid small molecules, oligomers containing lactic acid units, and high molecular polymers containing lactic acid units.

[0034] In summary, the technical effects that can be achieved by the present invention include at least:

[0035] 1) The lactic acid-containing composition of the present invention adopts a temperature-sensitive biological material preparation, which is a flowable liquid under low temperature conditions. When entering the body, it spontaneously forms a physical gel at body temperature and can be effectively sustained-released in the body;

[0036] 2) The lactic acid-containing composition and the injection containing the composition disclosed in the present invention have excellent biocompatibility and safety, low immunogenicity, and will not induce excessive immune response, such as redness and swelling;

[0037] 3) The product designed by the present invention has the characteristic of high water content, which can achieve the effect of daily skin moisturizing;

[0038] 4) The product of the present invention is liquid at room temperature and forms a gel system in the body. During the entire degradation cycle in the body, it can slowly release lactic acid that stimulates the regeneration of collagen in skin tissue, and can effectively enhance the elasticity and firmness of the skin;

[0039] At the same time, the product designed by the present invention has a long sustained release period and a long-term retention of 1-8 weeks, which can achieve long-term improvement of skin quality and solve the problem that traditional medical beauty treatments require frequent operations;

[0040] 5) The products mentioned in the present invention have excellent compatibility with most auxiliary ingredients, and the functional design of the preparation can be achieved by adding auxiliary ingredients;

[0041] 6) The present invention not only surpasses the prior art in terms of enhancing the skin quality, but also brings more possibilities and flexibility to the field of skin care. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0043] Figure 1 The accompanying drawings are photographs showing the phenomenon of thermally induced gelation transformation of the injection solution P1 in Example 1 as the temperature changes;

[0044] Figure 2 The accompanying figure shows the rheological test results of the injection solution P1 in Example 16;

[0045] Figure 3 The accompanying drawings show the test results of the in vitro lactic acid release behavior of the D,L-lactic acid solution and the injection P1 in Example 17;

[0046] Figure 4 The accompanying drawing shows the test of the intradermal retention time of the injection in Example 18;

[0047] Figure 5 The attached figure shows the evaluation results of the effects of the amphiphilic polymer, lactic acid and injection solution P1 in Example 21 on stimulating intradermal collagen regeneration.

[0048] Figure 6 The attached figure shows the evaluation results of the effect of injection solution P1 in Example 22 on stimulating intradermal collagen regeneration. DETAILED DESCRIPTION

[0049] 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, 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.

[0050] Example 1

[0051] This embodiment provides an injection solution P1, comprising:

[0052] The molecular weights of the polyether-polyester block copolymer PLGA-PEG-PLGA triblock copolymer are 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4. The mass fraction of D,L-lactic acid in the system is 0.2wt%.

[0053] According to the above configuration, the injection solution P1 is specifically:

[0054] Step (1): 7.5 g PLGA 1150 -PEG 1500 -PLGA 1150 and 7.5 g PLGA 1450 -PEG 1000 -PLGA 1450 Place in deionized water and stir under magnetic force at 4°C to completely dissolve the polymer to form a polymer aqueous solution with a polymer concentration of 25 wt%;

[0055] Step (2): add 0.2 g of D,L-lactic acid to the polymer solution obtained in step (1), dilute with deionized water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P1.

[0056] The injection solution P1 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0057] The obtained injection solution P1 was placed at 4°C to observe the solution state, placed at 37°C to observe the gel state, and placed at 50°C to observe the precipitation state. The results are as follows: Figure 1 shown.

[0058] Example 2

[0059] This embodiment provides an injection solution P2, comprising:

[0060] The polyether-polyester block copolymer is an mPEG-PLGA diblock copolymer with a molecular weight of 750-1850, wherein the content ratio of glycolic acid to lactic acid units is 1:4, and the mass fraction of L-lactic acid in the system is 0.2wt%.

[0061] According to the above configuration of injection solution P2, specifically,

[0062] Step (1): 15 g mPEG 750 -PLGA 1850 The mixture was placed in deionized water and stirred at 4° C. to fully dissolve the polymer, thereby forming a polymer solution with a polymer concentration of 20 wt %.

[0063] Step (2): add 0.2 g of D,L-lactic acid to the polymer solution obtained in step (1), dilute with water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P2.

[0064] The injection solution P2 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0065] Example 3

[0066] This embodiment provides an injection solution P3, comprising:

[0067] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer with a molecular weight of 1850-1500-1850, wherein the content ratio of glycolic acid to lactic acid units is 1:4, and the mass fraction of D,L-lactic acid in the system is 0.2wt%.

[0068] According to the above configuration of injection solution P3, specifically,

[0069] Step (1): 15 g PLGA 1850 -PEG 1500 -PLGA 1850 The mixture was placed in deionized water and stirred with magnetic force at 4° C. to fully dissolve the polymer, thereby forming a polymer solution with a polymer concentration of 25 wt %.

[0070] Step (2): add 0.2 g of D,L-lactic acid to the polymer solution obtained in step (1), dilute with water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P3.

[0071] The injection solution P3 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0072] Example 4

[0073] This embodiment provides an injection solution P4, comprising:

[0074] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer with a molecular weight of 1200-1000-1200, wherein the content ratio of glycolic acid to lactic acid units is 1:4, and the mass fraction of D-lactic acid in the system is 0.2wt%.

[0075] According to the above configuration of injection solution P4, specifically,

[0076] Step (1): 15 g PLGA 1200 -PEG 1000 -PLGA 1200 The polymer was completely dissolved in deionized water under magnetic stirring at 4° C. to form a polymer solution with a polymer concentration of 25 wt %.

[0077] Step (2): add 0.2 g of D-lactic acid to the polymer solution obtained in step (1), dilute with deionized water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P4.

[0078] The injection solution P4 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0079] Example 5

[0080] This embodiment provides an injection solution P5, comprising:

[0081] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0082] According to the above configuration of injection solution P5, specifically,

[0083] Step (1): 7.5 g PLGA 1150 -PEG 1500 -PLGA 1150 and 7.5 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4°C to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 25 wt%.

[0084] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 15 wt %, and stir at 4° C. to form injection solution P5.

[0085] The injection solution P5 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0086] Example 6

[0087] This embodiment provides an injection solution P6, comprising:

[0088] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, and the molecular weights are 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4, and the mass fraction of D,L-lactic acid in the system is 2wt%.

[0089] According to the above configuration, the injection solution P6 is specifically,

[0090] Step (1): 7.5 g PLGA 1150 -PEG 1500 -PLGA 1150 and 7.5 g PLGA 1450-PEG 1000 -PLGA 1450 The mixture was placed in deionized water and stirred with magnetic force at 4° C. to fully dissolve the polymer, thereby forming a polymer solution with a polymer concentration of 25 wt %.

[0091] Step (2): Add 2 g of D,L-lactic acid and 0.2 g of calcium carbonate to the polymer solution obtained in step (1), dilute with deionized water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P6.

[0092] The injection solution P6 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0093] Example 7

[0094] This embodiment provides an injection solution P7, comprising:

[0095] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4. The mass fraction of D,L-lactic acid in the system is 2wt%.

[0096] According to the above configuration injection solution P7, specifically,

[0097] Step (1): 7.5 g PLGA 1150 -PEG 1500 -PLGA 1150 and 7.5 g PLGA 1450 -PEG 1000 -PLGA 1450 Place in deionized water and stir magnetically at 4°C to completely dissolve the polymer to form a polymer solution with a polymer concentration of 25 wt%.

[0098] Step (2): add 2 g D, L-lactic acid, 0.02 g lidocaine, 0.2 g calcium carbonate and 0.05 g vitamin C to the polymer solution obtained in step (1), dilute with deionized water to a polymer concentration of 15 wt %, and stir at 4° C. to form injection solution P7.

[0099] The injection solution P7 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0100] Example 8

[0101] This embodiment provides an injection solution P8, comprising:

[0102] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1: 1. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0103] According to the above configuration of injection solution P8, specifically,

[0104] Step (1): 10 g PLGA 1150 -PEG 1500 -PLGA 1150 and 5 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4°C to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 25 wt%.

[0105] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 15 wt %, and stir at 4° C. to form injection solution P5.

[0106] The injection solution P8 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0107] Example 9

[0108] This embodiment provides an injection solution P9, comprising:

[0109] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:8. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0110] According to the above configuration of injection solution P9, specifically,

[0111] Step (1): 10 g PLGA 1150 -PEG 1500 -PLGA 1150 and 5 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4°C to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 25 wt%.

[0112] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 15 wt %, and stir at 4° C. to form injection solution P5.

[0113] The injection solution P9 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0114] Example 10

[0115] This embodiment provides an injection solution P10, comprising:

[0116] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1: 1. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0117] According to the above configuration of the injection solution P10, specifically,

[0118] Step (1): 5 g PLGA 1150 -PEG 1500 -PLGA 1150 and 10 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4°C to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 25 wt%.

[0119] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 15 wt %, and stir at 4° C. to form injection solution P5.

[0120] The injection solution P10 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0121] Embodiment 11

[0122] This embodiment provides an injection solution P11, comprising:

[0123] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0124] According to the above configuration of the injection solution P11, specifically,

[0125] Step (1): 6 g PLGA 1150 -PEG 1500 -PLGA 1150 and 6 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4°C to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 25 wt%.

[0126] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 12 wt %, and stir at 4° C. to form injection solution P5.

[0127] The injection solution P11 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0128] Example 12

[0129] This embodiment provides an injection solution P12, comprising:

[0130] The polyether-polyester block copolymer is a PLGA-PEG-PLGA triblock copolymer, with molecular weights of 1150-1500-1150 and 1450-1000-1450, respectively, wherein the content ratio of glycolic acid to lactic acid units is 1:4. The mass fraction of D,L-lactic acid in the system is 0.01wt%.

[0131] According to the above configuration of injection solution P12, specifically,

[0132] Step (1): 15 g PLGA 1150 -PEG 1500 -PLGA 1150 and 15 g PLGA 1450 -PEG 1000 -PLGA 1450 The polymer was placed in deionized water and stirred with magnetic force at 4° C. to completely dissolve the polymer, thereby preparing a polymer solution with a polymer concentration of 35 wt %.

[0133] Step (2): Add 0.01 g of D,L-lactic acid to the polymer solution prepared in step (1), add deionized water to dilute to a polymer concentration of 30 wt %, and stir at 4° C. to form injection solution P5.

[0134] The injection solution P12 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0135] Example 13

[0136] This embodiment provides an injection solution P13, comprising:

[0137] The polyether-polyester block copolymer is a PDLLA-PEG-PDLLA triblock copolymer with a molecular weight of 1850-1500-1850, and the mass fraction of D,L-lactic acid in the system is 0.2wt%.

[0138] According to the above configuration of injection solution P13, specifically,

[0139] Step (1): 15 g PDLLA 1850 -PEG 1500 -PDLLA 1850 The mixture was placed in deionized water and stirred with magnetic force at 4° C. to fully dissolve the polymer, thereby forming a polymer solution with a polymer concentration of 25 wt %.

[0140] Step (2): add 0.2 g of D,L-lactic acid to the polymer solution obtained in step (1), dilute with water to a polymer concentration of 15 wt %, and stir at 4° C. to form an injection solution P3.

[0141] The injection solution P13 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0142] Embodiment 14

[0143] This embodiment provides an injection solution P14, comprising:

[0144] The polyether-polyester block copolymer is a PLLA-PEG-PLLA triblock copolymer with a molecular weight of 1850-1500-1850. The mass fraction of L-lactic acid in the system is 0.2 wt%.

[0145] According to the above configuration of injection solution P14, specifically,

[0146] Step (1): 15 g PLLA 1850 -PEG 1500 -PLLA 1850 The mixture was placed in deionized water and stirred with magnetic force at 4° C. to fully dissolve the polymer, thereby forming a polymer solution with a polymer concentration of 25 wt %.

[0147] Step (2): 0.2 g of L-lactic acid was added to the polymer solution obtained in step (1), and water was added to dilute the solution to a polymer concentration of 15 wt %, and the mixture was stirred at 4° C. to form an injection solution P3.

[0148] The injection solution P14 can be injected into the skin or subcutaneous area through a skin injection pump to form a physical gel in situ.

[0149] Example 15

[0150] This example provides an injection P15, including:

[0151] The polyether-polyester block copolymer is a PDLA-PEG-PDLA triblock copolymer with a molecular weight of 1850-1500-1850, and the mass fraction of D-lactic acid in the system is 0.2 wt%.

[0152] Configure the injection P15 according to the above, specifically

[0153] Step (1): Place 15 g of PDLA 1850 -PEG 1500 -PDLA 1850 in deionized water, and magnetically stir at 4 °C to fully dissolve the polymer to form a polymer solution with a polymer concentration of 25 wt%.

[0154] Step (2): Add 0.2 g of D-lactic acid to the polymer solution obtained in step (1), and add water to dilute to a polymer concentration of 15 wt%, and stir and mix evenly at 4 °C to form injection P3.

[0155] This injection P15 can be injected into the intradermal or subcutaneous site through a skin injection pump to form a physical gel in situ.

[0156] Example 16

[0157] Rheological property test:

[0158] Use a rotational dynamic rheometer to measure the storage modulus (G') and loss modulus (G") of the injection in Example 1 at different temperatures to determine the thermosensitivity of the preparation. As Figure 2 shown, injection P1 shows a low-viscosity liquid at room temperature, and as the temperature rises to the human body temperature, its viscosity increases rapidly to form a stable physical gel.

[0159] Example 17

[0160] Evaluation of the in vitro lactic acid release behavior of the preparation:

[0161] The specific experimental method is: 1 mL of D,L-lactic acid solution (0.2% mass fraction) and 1 mL of injection solution P1 in Example 1 are pre-filled in the release tube, respectively. After equilibration at 37 degrees Celsius for 10 minutes, 10 mL of PBS buffer is added respectively, and the tube is placed in a water bath shaker to start timing. 2 mL of the upper release liquid is removed on the 1st day, 3rd day, 7th day, 14th day, 28th day, and 35th day, and 2 mL of fresh PBS buffer is added. An appropriate amount of sodium hydroxide solution is added to the obtained release liquid and boiled to convert the lactic acid and its derivatives therein into sodium lactate. The lactic acid unit content in the release liquid is analyzed by high performance liquid chromatography. The results are as follows: Figure 3 The results showed that compared with the free lactic acid solution, the injection solution could slowly release lactic acid and its derivatives containing lactic acid units during the entire degradation cycle.

[0162] Embodiment 18

[0163] In vivo maintenance time test:

[0164] The specific experimental method is as follows: first, a polymer with a fluorescent group is prepared, and then a polyether-polyester block copolymer PLGA is prepared. 1850 -PEG 1500 -PLGA 1850 Rhodamine B was grafted at both ends. A trace amount of the obtained fluorescent modified polymer was added to the injection solution obtained in Example 3 to form a fluorescent labeled injection solution. 90 microliters of the above injection solution was injected into the skin of SD rats in 9 arrays in equal amounts using a skin injection pump. The fluorescence signal intensity at the injection site at different time points was analyzed by in vivo fluorescence imaging technology to characterize the retention time of the injection solution in the skin. The results showed that the injection solution remained in the skin for 3-4 weeks ( Figure 4 ).

[0165] Embodiment 19

[0166] Evaluation of the compatibility of injections with skin:

[0167] The specific experimental method is as follows: female SD rats raised for 8 weeks were divided into 3 groups, each with 15 rats, namely PBS group, hyaluronic acid group and injection group. The back hair of all rats was removed, and then the experimental samples were injected into the skin of the back of the rats using a skin injection pump. The PBS group was injected with PBS solution, the hyaluronic acid group was injected with 1wt% hyaluronic acid solution, and the injection group was injected with injection solution P1 prepared in Example 1. The injection dose was a single injection of 9 points, and the cumulative injection volume was 90 microliters.

[0168] The skin appearance of the implanted area was observed every day for 4 weeks after implantation to see if there was redness, swelling or bulge, and the local tissue of the injected area was touched to see if there was nodule or granulation tissue proliferation. The experimental results are shown in the following table (Table 1):

[0169] Table 1 Skin appearance reaction at the implantation site

[0170]

[0171] Embodiment 20

[0172] Evaluation of the skin sensitization of the injection:

[0173] The evaluation method is the "maximum dose method" in the guinea pig sensitization experiment. The entire experimental process refers to the guinea pig sensitization experiment process specified in GB / T16886.10-2017. The brief process is as follows: First, the adult albino guinea pigs were divided into 3 groups, including 5 guinea pigs in the negative control group (normal saline), 5 guinea pigs in the positive control group (2,4-dinitrochlorobenzene), and 10 guinea pigs in the experimental group (injection). The concentration of 2,4-dinitrochlorobenzene used was 0.5wt%, and the injection was the injection P1 of Example 1. During the intradermal induction period, each group of experimental samples was injected intradermally into the guinea pig. After one week, the local induction period began, and the test sample was applied to the skin of the injection point on the back of the guinea pig, and then covered with a sealing patch for 48 hours. After two weeks of continued feeding, the excitation period began, and the test sample was applied to the skin of the injection point on the back of the guinea pig again, and then covered with a sealing patch for 24 hours. The skin reactions of the guinea pigs were examined 24 hours and 48 hours after the treatment, and the skin sensitization reactions were scored using the Magnusson and Kligman grading system (Table 2).

[0174] Table 2Magnusson and Kligman classification

[0175]

[0176] The following are the scoring results of the guinea pig sensitization experiment (Table 3):

[0177] Table 3 Scoring results of guinea pig sensitization experiment

[0178]

[0179] The data show that the polyether-polyester block copolymer is non-sensitizing to the skin, has good biocompatibility, and is suitable for skin injection.

[0180] Embodiment 21

[0181] Comparison of the effects of D,L-lactic acid, amphiphilic polymers and a combination of the two (D,L-lactic acid + amphiphilic polymers) on promoting collagen production in skin fibroblasts:

[0182] 10 5Mouse skin fibroblast L929 cells were seeded in 6-well plates and cultured in serum-free medium for 12 h after the cells adhered to the plate. Subsequently, D,L-lactic acid (0.2 wt%), amphiphilic polymer (0.5 wt%, polymer is PLGA) were used to culture the cells. 1150 -PEG 1500 -PLGA 1150 PLGA 1450 -PEG 1000 -PLGA 1450 The cells were cultured with 2 mL of culture medium of Example 1P1 injection (0.5 wt%) and a 1:1 blend, wherein the ratio of glycolic acid to lactic acid units was 1:4. The supernatant was collected after 1 day, and the amount of collagen type I and type III in the supernatant was detected using an ELISA kit. Figure 5 The test analysis diagram of the D,L-lactic acid group, the amphiphilic polymer group and the combination group (the statistical significance between the two groups was evaluated by variance analysis. "**" means p<0.01; "***" means p<0.001; "ns" means "not significant", i.e., it did not reach statistical significance). The experimental results show that the combination treatment is better than the single polymer treatment in promoting the secretion of collagen in skin fibroblasts.

[0183] Embodiment 22

[0184] Evaluation of the effect of injection on skin collagen regeneration:

[0185] The specific experimental method is as follows: female SD rats raised for 8 weeks were divided into 3 groups, each with 15 rats, namely PBS group, hyaluronic acid group (HA group) and injection group. The back hair of all rats was removed, and then the experimental samples were injected into the skin of the back of the rats using a skin injection pump. The PBS group was injected with PBS solution; the HA group was injected with 1wt% hyaluronic acid with a molecular weight of 200-400kDa; the injection group was injected with injection solution P1 prepared in Example 1. The injection dose was a single injection of 9 points, and the cumulative injection volume was 90 microliters.

[0186] The experimental animals were killed on the 7th, 14th and 28th day after the injection, and skin samples were collected. The collagen of the skin tissue samples was stained using the histological Masson staining technique to evaluate the effect of skin collagen regeneration. Figure 6 The following is a quantitative analysis of the staining of skin samples from the PBS group, HA group, and injection group (the statistical significance between the two groups was evaluated using analysis of variance. "*" indicates p<0.05, and "**" indicates p<0.01). The experimental results show that the injection can significantly promote the synthesis of skin collagen, reflecting its value in improving skin quality.

[0187] The PBS buffer or PBS solution used in the above examples is 1xPBS buffer.

[0188] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0189] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the concept or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A composition containing lactic acid, characterized in that include: Amphiphilic polymer and lactic acid; Wherein, the mass ratio of the amphiphilic polymer to the lactic acid is (2-40) g:(0.01-2) g.

2. A lactic acid-containing composition according to claim 1, characterized in that: The amphiphilic polymer is a polyether A-polyester B block copolymer, including an ABA or BAB type triblock copolymer, an AB type diblock copolymer, and an AgB or BgA type graft copolymer.

3. A lactic acid-containing composition according to claim 2, characterized in that: The polyether A block is polyethylene glycol with a molecular weight of 200-5000, and the polyester B block is an aliphatic polyester with a molecular weight of 200-5000.

4. A lactic acid-containing composition according to claim 2, characterized in that: The polyester B block comprises at least one of the following lactide copolymers: poly D,L-lactide, poly D-lactide or poly L-lactide; and further comprises: one or more of polyglycolide, poly ε-caprolactone, poly δ-valerolactone, polycarbonate, polyamide or polyether ester.

5. A lactic acid-containing composition according to claim 1, characterized in that: The lactic acid includes one or a mixture of D-lactic acid, L-lactic acid, D, L-lactic acid.

6. Use of a lactic acid-containing composition according to any one of claims 1 to 5 in skin care products and medical cosmetic products, wherein the product is preferably an injection for improving skin elasticity and firmness, and more preferably an injection for promoting skin collagen regeneration.

7. An injection, characterized in that: A composition comprising lactic acid as described in any one of claims 1 to 5.

8. An injection according to claim 7, characterized in that: The mass fraction of the amphiphilic polymer is 2wt%-40wt%; The mass fraction of the lactic acid is 0.01 wt % to 2 wt %.

9. An injection according to claim 7, characterized in that: Also includes: A combination of one or more of isotonic agents, pH regulators, analgesics, whitening factors, moisturizing factors, anti-wrinkle factors, and antioxidant factors; The isotonic agent includes one or more of sodium chloride, glycerol, glucose, and phosphate; The pH regulator includes one or more of calcium carbonate, sodium carbonate, and sodium bicarbonate; The analgesic comprises one or more of diclofenac sodium, lidocaine, flurbiprofen axetil, parecoxib sodium, ketorolac tromethamine, and celecoxib; The whitening factor includes one or more of salicylic acid, vitamin C, glycoside, asiatica glycoside, arbutin, kojic acid, and niacinamide; The moisturizing factor includes one or more of glycerin, urea, and hyaluronic acid; The anti-wrinkle factor comprises gelatin and / or collagen; The antioxidant factors include vitamin E and / or tea polyphenols.

10. A method for preparing an injection, characterized in that: Specifically include: The composition according to any one of claims 1 to 5 is used as an effective ingredient or is prepared according to any one of claims 7 to 9 as an injection.

11. The method for preparing the injection according to claim 10, characterized in that: Firstly, the amphiphilic polymer is dissolved in a proper amount of solvent to form a polymer solution, and then lactic acid is dissolved in the obtained polymer solution to form an injection solution.

12. The injection according to any one of claims 7 to 9 or the injection obtained by the preparation method of claim 10 or 11, characterized in that: The solution-gel phase transition temperature of the injection is 4-50°C, and the gel-precipitation phase transition temperature is 30-80°C.

13. An injection according to any one of claims 7 to 9 or an injection obtained by the preparation method of claim 10 or 11, characterized in that: The biodegradation period of the injection is 1-8 weeks, including the release of lactic acid in the initial stage of degradation and the release of lactic acid and its derivatives produced by the degradation of the amphiphilic polymer in the middle and late stages of degradation.

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