A skin repair, waterproof, transparent hyaluronic acid-based Janus film and a preparation method thereof

Abstract

The application provides a skin care Janus film. Specifically, the application provides a skin care waterproof hyaluronic acid-based Janus film, which has a hydrophilic layer and a hydrophobic layer arranged in an up-down mode, and the hydrophilic layer is in contact with the skin, wherein the hydrophilic layer is a hyaluronic acid film, and the hydrophobic layer is a polysiloxane film. The Janus biological film has good skin adhesion, air permeability, waterproofness, moisturizing and other integrated functions.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of dermatological applications, in particular to a waterproof hyaluronic acid-based Janus film for skin repair, and a preparation method and application thereof. BACKGROUND

[0002] Skin is the largest organ of the human body, a biologically active window for interaction between the inside and outside of the body, and maintaining the integrity of the skin structure and the skin barrier is the key to maintaining human homeostasis. Skin barrier damage, such as atopic dermatitis, psoriasis, wound healing, etc. is a common skin damage in human history, and has become a major public health problem worldwide. At present, researchers have developed many advanced biomedical materials and technologies to repair and promote skin health.

[0003] Hyaluronic acid (HA) is the extracellular matrix of the skin, which is involved in the processes of inflammation, cell migration, proliferation, differentiation, etc. Developing skin repair materials based on hyaluronic acid (HA) has excellent application prospects. Dai et al. developed a hyaluronic acid phosphate coordination Ag + hydrogel, which inhibits the growth of bacteria on the wound surface and accelerates wound healing. Wu et al. prepared a nanogel based on hyaluronic acid and polyvinyl alcohol for efficient antibacterial properties and wound healing.

[0004] Most of the current hyaluronic acid-containing care materials are complex to prepare, involve multiple reactions, and do not have film-forming properties. Film-forming care materials (facial masks) themselves have no care efficacy and mainly rely on the adsorption capacity to load efficacy-type essences for action on the site. At the same time, the best care film material for damaged skin needs to meet three properties: ① waterproof performance to protect the damaged skin layer; ② adhesion performance to protect the damaged site for a long time; and ③ repair function to have a certain care efficacy for the damaged layer. Currently, the main repair materials for damaged skin on the market are water-soluble film-forming gels, and there is no care film material that combines waterproof and adhesive properties.

[0005] Therefore, it is still a challenge in the current research field to design a skin care material that has waterproof, adhesive, and skin repair functions. SUMMARY

[0006] The purpose of the present application is to provide a functional integrated skin repair biomaterial with waterproof, skin adhesive, and skin repair functions.

[0007] In a first aspect of the present application, a skin repair Janus film is provided, which has a hydrophilic layer and a hydrophobic layer, the hydrophilic layer and the hydrophobic layer being arranged in an up-down manner,

[0008] wherein the hydrophilic layer is a hyaluronic acid film, and the hydrophobic layer is a polysiloxane film;

[0009] The skin care Janus film is obtained by a method comprising the following steps:

[0010] The water phase, oil phase, emulsifier, catalyst and dispersant are mixed, left to stand, and then solidified to obtain the skin care Janus film.

[0011] The oil phase comprises end-vinyl silicone oil and low-viscosity silicone oil, and the water phase comprises water and hyaluronic acid or a salt thereof.

[0012] In another preferred embodiment, the hydrophilic layer is in contact with the skin.

[0013] In another preferred embodiment, the hyaluronic acid or a salt thereof is selected from the group consisting of hyaluronic acid, sodium hyaluronate, potassium hyaluronate, or a combination thereof.

[0014] In another preferred embodiment, the hydrophilic layer further comprises other water-soluble active ingredients, preferably niacinamide, vitamin C, ascorbic acid, arbutin, Chinese herbal extract.

[0015] In another preferred embodiment, the molecular weight of the hyaluronic acid or a salt thereof is 5.0 x 10 5 ~ 2.0 x 10 6 kDa.

[0016] In another preferred embodiment, the end-vinyl silicone oil is selected from the group consisting of end-vinyl dimethicone, end-vinyl polymethylvinylsiloxane, monovinyl terminated dimethyl (siloxane and polysiloxane), vinyl trimethoxysilane and ethylene polymer, or a combination thereof.

[0017] In another preferred embodiment, the end-vinyl silicone oil comprises end-vinyl dimethicone, vinyl trimethoxysilane and ethylene polymer, and end-vinyl polymethylvinylsiloxane.

[0018] In another preferred embodiment, the low-viscosity silicone oil is selected from the group consisting of dimethicone, alkyl dimethicone, dimethicone copolyol, dimethicone alcohol ester, hemi dimethicone, amino dimethicone, or a combination thereof.

[0019] In another preferred embodiment, the low-viscosity silicone oil comprises dimethicone and alkyl dimethicone.

[0020] In another preferred embodiment, the mass ratio of the end-vinyl silicone oil to the low-viscosity silicone oil is 1:10-10:1, preferably 1:4-8:1, more preferably 1:5-5:1, for example 1:2~2:1, 1:1.5~1.5:1, 1:1.

[0021] In another preferred embodiment, the ratio of the thickness of the hydrophilic layer to the thickness of the hydrophobic layer is 5~1:1.

[0022] In another preferred embodiment, the hydrophilic layer has a thickness of 50-500 μm, preferably 100-500 μm, for example 200 μm, 250 μm, 300 μm, 350 μm, 400 μm.

[0023] In another preferred embodiment, the hydrophobic layer has a thickness of 10-200 μm, preferably 20-150 μm, for example 50 μm, 80 μm, 100 μm, 150 μm.

[0024] In another preferred embodiment, the skin care Janus film has one or more features selected from the group consisting of:

[0025] (1) has skin self-adaptability, can still closely adhere to the skin at the bending site;

[0026] (2) the moisture content of the skin is increased by more than 30% within 2h, preferably more than 50%.

[0027] In another preferred embodiment, the method comprises the following steps:

[0028] (a) preparing component A: mixing the water phase, the oil phase and the emulsifier to obtain an emulsion;

[0029] (b) preparing component B: mixing the catalyst and the dispersing agent to obtain component B;

[0030] (c) mixing component A obtained in step (a) and component B obtained in step (b), standing, and then solidifying to obtain the skin care Janus film.

[0031] In another preferred embodiment, the oil phase is a liquid silicone oil.

[0032] In another preferred embodiment, the oil phase comprises the following ingredients based on the total weight of the oil phase:

[0033] vinyl-terminated silicone oil 10-60 wt%, preferably 20-60 wt%, for example 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%;

[0034] low-viscosity silicone oil 10-60 wt%, preferably 20-60 wt%, for example 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%.

[0035] In another preferred embodiment, the oil phase comprises the following ingredients based on the total weight of the oil phase:

[0036] vinyl-terminated polydimethylsiloxane 10-50 wt%, for example 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%;

[0037] vinyl terminated polydimethylvinylsiloxane 10-50 wt%, for example 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%;

[0038] vinyl trimethoxysilane with ethylene 10-50 wt%, for example 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%;

[0039] polydimethylsiloxane 10-50 wt%, for example 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 50 wt%;

[0040] alkyl dimethicone 1-30 wt%, for example 2 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%.

[0041] In another preferred embodiment, the aqueous phase comprises the following ingredients, calculated on the total weight of the aqueous phase:

[0042] hyaluronic acid or a salt thereof 0.05-5 wt%, preferably 0.08-4 wt%, more preferably 0.1-3 wt%, for example 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%; and

[0043] water 60-99.99 wt%, preferably 70-99.9 wt%, more preferably 75-99.9 wt%, for example 80 wt%, 90 wt%, 95 wt%, 98 wt%, 99 wt%, 99.5 wt%, 99.7 wt%, 99.8 wt%.

[0044] In another preferred embodiment, the mass ratio of the hyaluronic acid or a salt thereof and water is 1 : 10-200, preferably 1 : 25-1 : 100, more preferably 1 : 30-1 : 70, for example 1 : 40, 1 : 50, 1 : 60.

[0045] In another preferred embodiment, the emulsifier is selected from the group consisting of polyglyceryl-3 distearoxydimethicone, PEG-9 dimethicone crosspolymer, PEG-3 dimethicone, lauryl PEG-9 dimethicone crosspolymer, bis-PEG / PPG-20 / 5 dimethicone (and) methoxy PEG / PPG-25 / 4 dimethicone (and) caprylic / capric triglyceride, cetyl PEG / PPG-10 / 1 dimethicone, cyclopentasiloxane (and) PEG / PPG-18 / 18 dimethicone, or a combination thereof.

[0046] In another preferred embodiment, the emulsifier comprises polyglyceryl-3 distearoxy dimethicone and lauryl PEG-9 polydimethylsiloxyethyl dimethicone.

[0047] In another preferred embodiment, the mass ratio of polyglyceryl-3 distearoxy dimethicone and lauryl PEG-9 polydimethylsiloxyethyl dimethicone in the emulsifier is 5:1 to 1:5, preferably 2:1 to 1:2, more preferably 1:1.5 to 1.5:1, for example 1:1.

[0048] In another preferred embodiment, the mass ratio of the oil phase to the B component is 1:5 to 100, preferably 1:10 to 100, more preferably 1:10 to 1:50, for example 1:20, 1:30, 1:40.

[0049] In another preferred embodiment, the catalyst is selected from the group consisting of platinum catalyst, Speier catalyst, Karstedt catalyst, or a combination thereof.

[0050] In another preferred embodiment, the dispersant is selected from the group consisting of tetramethyltetavinylcyclotetrasiloxane, dimethylmethylhydro(siloxane and polysiloxane), or a combination thereof.

[0051] In another preferred embodiment, the mass ratio of the catalyst to the dispersant is 1:1 x 10 -7 -1:1 x 10 -5 , preferably 1:5 x 10 -7 -1:1 x 10 -5 , for example 1:8 x 10 -7 wt%, 1:1 x 10 -6 wt%, 1:2 x 10 -6 wt%, 1:5 x 10 - 6 wt%, 1:8 x 10 -6 wt%.

[0052] In another preferred embodiment, the reaction raw materials of the method comprise the following components, calculated based on the total weight of the reaction raw materials:

[0053] 15-55 wt% of the oil phase, preferably 20-55 wt%, more preferably 35-55 wt%, for example 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%;

[0054] 1-5 wt% of the emulsifier, preferably 1-4 wt%, for example 1.2 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%;

[0055] 45-85wt% of aqueous phase, preferably 45-70wt%, more preferably 45-65wt%, for example 45wt%, 50wt%, 55wt%, 60wt%, 65wt%;

[0056] Catalyst 1×10 -6 -5×10 -4 wt%, preferably 1×10 -6 -5×10 -5 wt%, preferably 1×10 -6 -10×10 - 6 wt%, for example 2×10 -6 wt%, 5×10 -6 wt%, 8×10 -6 wt%;

[0057] Dispersant 1-5wt%, preferably 1-4wt%, for example 1.2wt%, 1.5wt%, 2wt%, 2.2wt%, 2.5wt%, 3wt%, 3.5wt%.

[0058] In another preferred embodiment, the step (a) comprises the following steps:

[0059] (1) mixing the oil phase with the emulsifier to obtain an oil phase system;

[0060] (2) mixing water and hyaluronic acid or a salt thereof to obtain an aqueous phase;

[0061] (3) The oil phase system is mixed with the water phase to obtain a metastable emulsion of component A.

[0062] In another preferred embodiment, the mixing temperature in step (1) is 10-40°C.

[0063] In another preferred embodiment, the mixing in step (1) is performed at 500 to 1500 rpm / min for 10 to 30 minutes.

[0064] In another preferred embodiment, the mixing temperature in step (2) is 10-40°C.

[0065] In another preferred embodiment, the mixing in step (2) is performed at 1000-1500 rpm / min for 60-120 min.

[0066] In another preferred embodiment, the mixing temperature in step (3) is 10-40°C.

[0067] In another preferred embodiment, the step (3) comprises: adding the aqueous phase to the stirred oil phase system (preferably at a rotation speed of 200 to 500 rpm / min), and mixing until a uniform emulsion is formed, namely component A.

[0068] In another preferred embodiment, the temperature of the mixing in step (b) is 10-40 °C.

[0069] In another preferred embodiment, the mixing in step (b) is 200-500 rpm / min stirring for 10-30 min.

[0070] In another preferred embodiment, in step (c), the mixing is carried out at 10-40 °C.

[0071] In another preferred embodiment, in step (c), the solidification is carried out at 35-95 °C, preferably 45 °C.

[0072] In another preferred embodiment, in step (c), the solidification is carried out for 2-24 h, preferably 2-5 h, for example 3 h.

[0073] In another preferred embodiment, in step (c), the standing is carried out at 10-40 °C.

[0074] In another preferred embodiment, in step (c), the standing is carried out for 12-36 h.

[0075] In a second aspect of the present application, there is provided a method for preparing a skin repair Janus film as described in the first aspect of the present application, by mixing an aqueous phase, an oil phase, an emulsifier, a catalyst and a dispersant, standing, and then solidifying to obtain the skin repair Janus film.

[0076] In another preferred embodiment, the method comprises the following steps:

[0077] (a) preparing component A: mixing an aqueous phase, an oil phase and an emulsifier to obtain an emulsion;

[0078] (b) preparing component B: mixing a catalyst and a dispersant to obtain component B;

[0079] (c) mixing component A obtained in step (a) and component B obtained in step (b), standing, and then solidifying to obtain the skin repair Janus film.

[0080] In another preferred embodiment, the method is as described in the method of the first aspect of the present application.

[0081] In a third aspect of the present application, there is provided the use of a skin repair Janus film as described in the first aspect of the present application for preparing a material for skin repair and / or promoting skin wound healing.

[0082] In another preferred embodiment, the material for skin repair and / or promoting skin wound healing is a film material.

[0083] In a fourth aspect of the present application, there is provided a cosmetic composition comprising the skin repair Janus film according to the first aspect of the present application, and a cosmetically acceptable carrier.

[0084] In another preferred embodiment, the cosmetic composition is a film material.

[0085] In another preferred embodiment, the cosmetic composition is selected from the group consisting of a facial mask, an eye mask, a lip mask, or a combination thereof.

[0086] In a fifth aspect of the present application, there is provided a medical material comprising the skin repair Janus film according to the first aspect of the present application.

[0087] In another preferred embodiment, the medical material is a skin wound dressing.

[0088] In a sixth aspect of the present application, there is provided a method of skin repair and / or promoting skin wound healing, applying the skin repair Janus film according to the first aspect of the present application, or the cosmetic composition according to the fourth aspect of the present application, or the medical material according to the fifth aspect of the present application, to a subject in need thereof.

[0089] In another preferred embodiment, the subject comprises a human, or a non-human mammal.

[0090] In a seventh aspect of the present application, there is provided a metastable emulsion comprising an oil phase, an aqueous phase, and an emulsifier;

[0091] wherein the oil phase comprises a vinyl-terminated silicone oil and a low viscosity silicone oil; the aqueous phase comprises hyaluronic acid or a salt thereof and water.

[0092] In another preferred embodiment, the oil phase, the aqueous phase, and the emulsifier are each independently as described in the first aspect of the present application.

[0093] In another preferred embodiment, the metastable emulsion is prepared by a method comprising the following steps:

[0094] (1) mixing the oil phase with the emulsifier to obtain an oil phase system;

[0095] (2) mixing water and hyaluronic acid or a salt thereof to obtain an aqueous phase;

[0096] (3) mixing the oil phase system with the aqueous phase to obtain the metastable emulsion.

[0097] In another preferred embodiment, the method is as described in step (a) of the second aspect of the present application.

[0098] It should be understood that, within the scope of the present application, each of the technical features of the present application described above and each of the technical features specifically described hereinafter (such as the examples) can be combined with each other to constitute a new or preferred technical solution. Due to the limited space, they will not be listed one by one here. BRIEF DESCRIPTION OF DRAWINGS

[0099] Figure 1 The schematic diagram of the steps for preparing the hyaluronic acid-based Janus film of the present application is shown.

[0100] Figure 2A The contact angle diagram of the hydrophobic surface of the hyaluronic acid-based Janus film is shown.

[0101] Figure 2B The contact angle diagram of the hydrophilic surface of the hyaluronic acid-based Janus film is shown.

[0102] Figure 3 The staining microscope diagram of the hyaluronic acid-based Janus film is shown.

[0103] Figure 4 The SEM diagram of the hyaluronic acid-based Janus film is shown.

[0104] Figure 5 The back of hand application picture of the hyaluronic acid-based Janus film is shown: (a) natural state of the back of hand; (b) stretched state of the back of hand.

[0105] Figure 6 The change of the skin moisture content before and after using the test product is shown. DETAILED DESCRIPTION

[0106] The present inventors have made extensive and in-depth research and for the first time discovered a hyaluronic acid-based skin repair Janus film with waterproofness, adhesion and skin repair functions.

[0107] The present application takes hyaluronic acid, which is widely distributed in mammalian tissues and extracellular matrix and has excellent biocompatibility, as the starting point, uses a simple emulsification technology to combine the silicon phase with the hyaluronic acid part to form a metastable system under certain conditions. Then the catalyst and the vinyl silicone oil in the system are subjected to interfacial crosslinking and solidification to form a film. Due to the destabilization of the system during solidification and crosslinking, the high molecular weight sodium hyaluronate is precipitated, and at the same time it is integrated with the silicon network structure. Thus, a skin repair Janus film with certain functions such as adhesion, occlusion, good skin adhesion, air permeability, waterproofness, moisturizing, etc. is formed, which has an upper layer of polysiloxane film and a lower layer of hyaluronic acid film. On this basis, the present application is completed.

[0108] TERMS

[0109] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0110] As used herein, the terms "comprising," "including," "containing," and variations thereof, are intended to be equivalent to the term "consisting of" and are inclusive of the elements listed thereafter. In other words, the terms "comprising," "including," and "containing" encompass the terms "consisting of" and "consisting essentially of."

[0111] As used herein, the term "about" when used in the context of a recited numerical value means that the value can vary from the recited value by not more than 1%. For example, as used herein, the expression "about 100" includes all values between 99 and 101 (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

[0112] Janus membrane

[0113] A Janus structure is a non-symmetrical structure with different chemical compositions or properties, and a Janus membrane is a membrane with anisotropy in the morphological structure or chemical properties of the two sides thereof, and has potential application value in the biomedical field such as drug delivery.

[0114] Skin care Janus membrane of the present application

[0115] As used herein, "skin care Janus membrane", "hyaluronic acid-based Janus membrane", and "Janus membrane of the present application" are used interchangeably to refer to a membrane that is formed spontaneously by cross-linking a polymer under the trigger of a curing agent, with sodium hyaluronate as the basic component and emulsified low-viscosity vinyl silicone oil forming a homogeneous system, and has the property of being double-sided.

[0116] The upper layer of the Janus membrane of the present application is a hydrophobic layer, i.e., a polysiloxane membrane, and the lower layer is a hydrophilic layer, i.e., a hyaluronic acid membrane. The hyaluronic acid in the lower layer has a certain adhesion to skin cells under the trigger of water, and thus has certain skin adhesion and care efficacy; the polysiloxane membrane in the upper layer has water resistance and certain skin self-adaptability.

[0117] After the Janus membrane of the present application is cured and formed at a certain temperature, it needs to be placed at room temperature for several hours to allow the water in the wet hydrophilic layer to evaporate in the air, so that the hydrophilic layer forms a sponge-like foamed cross-linked sodium hyaluronate network. At this time, the hydrophilic layer contains only a small amount of water.

[0118] The Janus membrane has anisotropy in the morphological structure and chemical properties of the two sides thereof, and has great application prospects in the fields of cosmetics, biological materials, and dermatological applications.

[0119] Medical material and / or cosmetic composition

[0120] The present application provides a medical material and / or cosmetic composition containing a safe and effective amount or a cosmetically effective amount of the Janus membrane of the present application.

[0121] In the present application, "safe and effective amount" means an amount of active ingredient sufficient to significantly improve the condition or symptom without causing serious side effects.

[0122] In the present application, the term "cosmetically effective amount" means an amount sufficient to substantially achieve the intended effect of the materials of the present application.

[0123] Pharmaceutically or cosmetically acceptable carriers are those conventionally utilized in the preparation or composition of formulations, including lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto.

[0124] As the carrier of the medical material and / or cosmetic composition of the present application, any conventional carrier can be used, and examples thereof include pure water, mineral water, ethanol, glycerin, squalene, 1,3-propanediol, 1,3-butanediol, castor oil, camellia oil, and liquid petrolatum.

[0125] The medical material and / or cosmetic composition of the present application can be formulated using pharmaceutically or cosmetically acceptable carriers and / or excipients according to a method easily performed by one of ordinary skill in the art to which the present application pertains, thereby prepared in a unit capacity form, or filled into a large capacity container. Specifically, the dosage form can be a film.

[0126] In the case of the film as the dosage form of the present application, as the carrier component, conventional adjuvants such as a thickening agent, a flavoring agent, a preservative, a humectant, an emulsifying agent, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, a surfactant, a suspending agent, an antioxidant, a preservative, a stabilizer, a solubilizing agent, a vitamin, and a perfume can be included.

[0127] The thickening agent can be divided into water-soluble natural organic thickening agent including hyaluronic acid, xanthan gum, starch; water-soluble organic semi-synthetic thickening agent including carboxymethyl cellulose, ethyl cellulose; water-soluble organic synthetic thickening agent including carbomer, polyvinyl alcohol, polyethylene glycol; inorganic micro-powder thickening agent including magnesium aluminum silicate, silicon dioxide, bentonite; modified inorganic micro-powder thickening agent including modified silicon dioxide, nepheline; organic micro-powder thickening agent including microcrystalline cellulose.

[0128] The humectant can include small molecule polyols such as glycerol, propylene glycol, or high molecular weight humectants such as hyaluronic acid and non-polyol humectants.

[0129] The preservative can include nipagin esters, including methyl ester, ethyl ester, propyl ester, butyl ester and the like; chlorphenesin, quaternary ammonium salt-15, sodium dehydroacetate and the like.

[0130] Preparation method

[0131] The present application adopts simple emulsification technology to combine the silicon phase and hyaluronic acid to form a metastable system under certain conditions. Then the catalyst and the vinyl silicone oil in the system are interfacially cross-linked and solidified into a film. Because the system is unstable during solidification and cross-linking, the high molecular weight sodium hyaluronate is precipitated, and at the same time is integrated with the silicon network structure. Due to the metastable state of the emulsion interface during the solidification process, the hydrophilic segment of the sodium hyaluronate molecule is expelled and repelled by the hydrophobic effect, thereby forming a hydrophilic layer and a silicone oil layer. The upper layer is a polysiloxane film, and the lower layer is a hyaluronic acid film. Finally, the system forms a hyaluronic acid-based Janus film which has certain flexibility, good skin adhesion, air permeability, waterproofness, moisturizing and other care functions.

[0132] The preparation method of the present application mainly includes two aspects:

[0133] (1) First, prepare a metastable state emulsion. The present application first selects an emulsifier with moderate interfacial tension for the water phase of sodium hyaluronate and the low viscosity silicone oil phase of the system, to prepare an emulsion based on the selected emulsifier, so that the two phases are in a metastable state under a certain shear rate.

[0134] (2) Prepare a Janus film with two-phase dissimilarity and mechanical properties. The metastable emulsion-curing agent mixed system is interfacially polymerized by chain initiation cross-linking under certain conditions; at the same time, the metastable emulsion loses the metastable condition (a certain shear rate), and the system is unstable under the gravitational potential, and interfacial precipitation occurs. Thus, a Janus film with two-phase dissimilarity and mechanical properties is formed.

[0135] The specific steps for preparing the Janus film of the present application include:

[0136] (1) Prepare the oil phase system: mix the oil phase and the emulsifier at room temperature to obtain a uniformly dispersed oil phase component;

[0137] (2) Preparation of aqueous phase system: the aqueous phase is mixed at room temperature to obtain uniformly dispersed aqueous phase components;

[0138] (3) Preparation of A component: the oil phase obtained in step (1) is stirred, and the aqueous phase system obtained in step (2) is added, and stirring is continued until a uniform emulsion is obtained, i.e. A component;

[0139] (4) Preparation of B component: the catalyst and dispersant are mixed at room temperature to obtain uniformly dispersed B component;

[0140] (5) Facilitating interfacial polymerization: the A component obtained in step (3) is stirred, and the B component obtained in step (4) is added, and stirring is continued until the system is uniform, then the system is left to stand in a 30*30mm mold for 12h, and then cured at 45℃ for 3h to form a skin repair and waterproof hyaluronic acid-based Janus film.

[0141] The main advantages of the present application include:

[0142] (1) The present application forms a double-layer film with Janus structural characteristics in the microstructure, and has excellent performance of hydrophilic on one side and water-resistant on the other side.

[0143] (2) The hyaluronic acid-based Janus film has certain skin adhesion, care efficacy, waterproofness, and certain skin self-adaptability.

[0144] (3) The hydrophilic layer of the present application has skin-friendly, skin repair functions, and can load functional active ingredients; the hydrophobic layer of the present application has softness and waterproofness.

[0145] (4) The present application has film-forming property, and is simple, practical and convenient to prepare.

[0146] The present application will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and not to limit the scope of the present application. The experimental methods in the following examples are not specified, and are usually carried out under conventional conditions or under conditions recommended by the manufacturer. Unless otherwise specified, percentages and parts are weight percentages and weight parts.

[0147] Example 1: Preparation method of hyaluronic acid-based Janus film

[0148] The preparation method of the hyaluronic acid-based Janus film is as shown in Figure 1 and specifically includes the following steps:

[0149] (1) Preparation of oil phase system: the mixed oil phase (1 g end-vinyl polydimethylsiloxane, 1 g end-vinyl polymethylvinylsiloxane, 1 g vinyltrimethoxysilane polymer of ethylene, 1.5 g polydimethylsiloxane, 0.5 g alkyl polydimethylsiloxane) and 0.2 g emulsifier (0.1 g polyglyceryl-3 disiloxane dimethyl polysiloxane, 0.1 g lauryl PEG-9 polydimethylsiloxane ethyl dimethyl polysiloxane) are mixed at room temperature for 10-30 min (500-1500 rpm / min) to obtain a uniformly dispersed oil phase component;

[0150] (2) Preparation of water phase system: the water phase (0.1 g sodium hyaluronate, 5 g water) is stirred at room temperature for 60-120 min (1000-1500 rpm / min) to obtain a uniformly dispersed water phase component;

[0151] (3) Preparation of component A: the oil phase component obtained in step (1) is stirred at a speed of 200-500 rpm / min, and the water phase component obtained in step (2) is added, and stirred for 10-30 min to obtain a uniform emulsion, thereby obtaining component A;

[0152] (4) Preparation of component B: 0.2 g of Karstedt catalyst and dimethyl methyl hydrogen (siloxane and polysiloxane) mixture (dispersant: catalyst = 1:1 x 10 -6 w / w) are stirred at room temperature for 10-30 min (200-500 rpm / min) to obtain a uniformly dispersed component B;

[0153] (5) Facilitating interfacial polymerization: the component A obtained in step (3) is stirred at a speed of 200-500 rpm / min, and the component B obtained in step (4) is added, and stirred for 10-30 min until the system is uniform, then 1 g of pre-cured sample is placed in a 30*30 mm mold for 12 h, and then cured at 45°C for 3 h to form a skin care and waterproof hyaluronic acid-based Janus film. The thickness of the hydrophobic layer is about 80 μm, and the thickness of the hydrophilic layer is about 220 μm.

[0154] Example 2: Hydrophobicity and hydrophilicity of the hyaluronic acid-based Janus film

[0155] The contact angle results of the upper and lower layers of the hyaluronic acid-based Janus film are shown in Figure 2A 、 Figure 2B .

[0156] It can be seen that the polysiloxane film layer of the upper layer is a hydrophobic layer, and the hyaluronic acid layer of the lower layer is a hydrophilic layer, which further proves that the anisotropic Janus structure of the upper and lower layers is successfully prepared.

[0157] The hyaluronic acid-based Janus film is dyed to more clearly illustrate the hydrophilic and hydrophobic properties of the film.

[0158] Dyeing step: ① Put the film section into water and soak for 1 h (allow the film system to fully absorb moisture, reduce the dyeing error of oil / water-soluble dye); ② immerse the section in a methylene blue aqueous solution for 30 min, remove the section and wipe off the excess dyeing solution with filter paper, and wash off the floating color with deionized water; ③ immerse the section again in a Sudan III ethanol solution for 30 min, remove the section and wipe off the excess dyeing solution with filter paper, and wash off the floating color with 50% ethanol to obtain the hyaluronic acid-based Janus film dyed on both sides. Then, microscopic observation is performed.

[0159] The dyeing microscopic image is shown in Figure 3 It can be seen that the upper polysiloxane film is dyed red due to the oil-soluble dye, and the lower hyaluronic acid film is dyed blue due to the water-soluble dye.

[0160] Example 3. Morphological characteristics of the hyaluronic acid-based Janus film

[0161] The scanning electron microscope image of the hyaluronic acid-based Janus film is shown in Figure 4

[0162] It can be clearly seen that the upper smooth hydrophobic polysiloxane film structure and the lower porous hyaluronic acid film.

[0163] Example 4. Skin self-adaptability and fit effect diagram of the hyaluronic acid-based Janus film

[0164] The photograph of the hyaluronic acid-based Janus film hydrophilic layer after being applied to the back of the hand after absorbing an appropriate amount of moisture is shown in Figure 5

[0165] It can be clearly seen that the hydrophilic layer of the film still closely adheres to the back of the hand at the curved part.

[0166] Example 5. Moisturizing performance diagram of the hyaluronic acid-based Janus film

[0167] Test conditions: test environment temperature: 20-22℃, relative humidity: 40-60%. The test site is located on the inner side of the left forearm of the subject, and a 2x2 cm area is marked near the palm in the middle of the forearm, selecting an area with no or few body hairs. 2 As a blank test area, another 2x2 cm area is marked in the direction of the elbow at a distance of ≥1 cm from the area. 2 As a sample test area. The subject exposes the test site, and the laboratory technician marks the area according to the test site during the subject's sitting in the laboratory at a temperature of 21±1℃ and a relative humidity of 50±5%.

[0168] ​​Test method: 1. Blank test: according to the test requirements, a certain size of cling film (the film is dipped in water and then attached) is attached to the test area of the subject; 2. Sample test: according to the test requirements, a certain size of hyaluronic acid-based Janus film is attached to the test area of the subject.

[0169] The test results, as shown in Figure 6 , it can be clearly seen that the hyaluronic acid-based Janus film has excellent skin moisturizing performance compared with the cling film control. The skin moisture content of the blank control group only fluctuates slightly within 2h, while the skin moisture content of the subject after attaching the Janus film of the present application for 2h increases from about 32.5% to about 52.5%, which is more than 60%, so the moisturizing performance of the Janus film is very excellent.

[0170] All the documents mentioned in the present application are incorporated by reference in the present application, as if each document is incorporated by reference individually. In addition, it should be understood that, after reading the above teaching of the present application, those skilled in the art can make various modifications or changes to the present application, and these equivalent forms also fall within the scope defined by the claims attached to the present application.

Claims

1. A skin-repairing Janus film, characterized in that, The skin care Janus film has a hydrophilic layer and a hydrophobic layer arranged in an up-down manner, wherein the hydrophilic layer is a hyaluronic acid film and the hydrophobic layer is a polysiloxane film. The skin care Janus film is obtained by a method comprising the following steps: mixing the water phase, the oil phase, the emulsifier, the catalyst and the dispersant, standing, and then curing to obtain the skin care Janus film; wherein the oil phase comprises end-vinyl silicone oil and low-viscosity silicone oil, and the water phase comprises water and hyaluronic acid or a salt thereof.

2. The skin treatment Janus film of claim 1, wherein, The hydrophilic layer is in contact with the skin.

3. The skin treatment Janus film of claim 1, wherein, The skin care Janus film comprises one or more features selected from the group consisting of: (a) the hyaluronic acid or a salt thereof is selected from the group consisting of hyaluronic acid, sodium hyaluronate, potassium hyaluronate, or a combination thereof; (b) the hyaluronic acid or salt thereof has a molecular weight of 5.0 x 10 5 ~ 2.0 x 10 6 kDa; (c) the end-vinyl silicone oil is selected from the group consisting of end-vinyl dimethicone, end-vinyl polymethylvinylsiloxane, monovinyl terminated dimethyl (siloxane and polysiloxane), vinyl trimethoxysilane and ethylene polymer, or a combination thereof; (d) the low-viscosity silicone oil is selected from the group consisting of dimethicone, alkyl dimethicone, dimethicone copolyol, dimethicone alcohol ester, hemi dimethicone, amino dimethicone, or a combination thereof.

4. The skin treatment Janus film of claim 1, wherein, The end-vinyl silicone oil comprises end-vinyl dimethicone, vinyl trimethoxysilane and ethylene polymer, and end-vinyl polymethylvinylsiloxane; and / or The low-viscosity silicone oil comprises dimethicone and alkyl dimethicone.

5. The skin treatment Janus film of claim 1, wherein, The ratio of the thickness of the hydrophilic layer to the thickness of the hydrophobic layer is 5-1:

1.

6. The skin treatment Janus film of claim 1, wherein, The thickness of the hydrophilic layer is 50-500 μm; The thickness of the hydrophobic layer is 10-200 μm.

7. The skin treatment Janus film of claim 6, wherein, The thickness of the hydrophilic layer is 100-500 μm; The thickness of the hydrophobic layer is 20-150 μm.

8. The skin treatment Janus film of claim 1, wherein, The skin care Janus film comprises one or more features selected from the group consisting of: (1) the oil phase comprises the following ingredients based on the total weight of the oil phase: end-vinyl silicone oil 10-60 wt%; low-viscosity silicone oil 10-60 wt%; (2) the water phase comprises the following ingredients based on the total weight of the water phase: hyaluronic acid or a salt thereof 0.05-5 wt%; and water 60-99.99 wt%; (3) the emulsifier is selected from the group consisting of polyglyceryl-3 disiloxane dimethicone, PEG-9 dimethicone ethyl dimethicone, PEG-3 dimethicone, lauryl PEG-9 dimethicone ethyl dimethicone, bis-PEG / PPG-20 / 5 PEG / PPG-20 / 5 dimethicone, and methoxy PEG / PPG-25 / 4 dimethicone and caprylic / capric triglyceride, cetyl polyglycol / polypropylene glycol-10 / 1 dimethyl silicone alcohol, cyclopentadimethicone, and PEG / PPG-18 / 18 dimethicone, or a combination thereof; (4) the catalyst is selected from the group consisting of platinum catalyst, Speier catalyst, Karstedt catalyst, or a combination thereof; (5) the dispersant is selected from the group consisting of tetramethyltetavinylcyclotetrasiloxane, dimethylmethylhydro(siloxane and polysiloxane), or a combination thereof.

9. The skin treatment Janus film of claim 1, wherein, The oil phase comprises the following ingredients based on the total weight of the oil phase:

10. The skin treatment Janus film of claim 1, wherein, The content of the raw materials of the method is calculated based on the total weight of the reaction raw materials:

11. The skin treatment Janus film of claim 1, wherein, The skin repair Janus film has one or more features selected from the group consisting of: (1) has skin self-adaptability, can still closely adhere to the skin at the bending part; (2) the moisture content of the skin is increased by more than 30% within 2h.

12. The skin treatment Janus film of claim 1, wherein, The method comprises the following steps: (a) preparing component A: mixing the water phase, the oil phase and the emulsifier to obtain an emulsion; (b) preparing component B: mixing the catalyst and the dispersant to obtain component B; (c) mixing component A obtained in step (a) and component B obtained in step (b), standing, and then solidifying to obtain the skin repair Janus film.

13. The skin treatment Janus film of claim 12, wherein, The method comprises one or more features selected from the group consisting of: (1) the mass ratio of the end-vinyl silicone oil to the low-viscosity silicone oil is 1:10-10:1; (2) the mass ratio of the hyaluronic acid or its salt to water is 1:10-200; (3) the mass ratio of the oil phase to component B is 20-200:1; (4) the mass ratio of the catalyst to the dispersant is 1 : 1 x 10 -7 -1:1 x 10 -5 ; (5) in step (c), the solidification is carried out at 35-95℃, and the solidification time is 2-24h; (6) in step (c), the standing is carried out at 10-40℃, and the standing time is 12-36h.

14. The skin treatment Janus film of claim 13, wherein, The method comprises one or more features selected from the group consisting of: (1) the mass ratio of the end-vinyl silicone oil to the low-viscosity silicone oil is 1:4-8:1; (2) the mass ratio of the hyaluronic acid or its salt to water is 1:25-1:100; (3) the mass ratio of the oil phase to component B is 25-100:1; (4) the mass ratio of the catalyst to the dispersant is 1 : 5 x 10 -7 -1 : 1 x 10 -5 .

15. The method for preparing the skin repairing Janus membrane according to claim 12, wherein: The step (a) comprises the following steps: (1) mixing the oil phase and the emulsifier to obtain an oil phase system; (2) mixing the water and the hyaluronic acid or its salt to obtain a water phase; (3) mixing the oil phase system and the water phase to obtain a metastable emulsion of component A.

16. A method of preparing a skin repair Janus film according to any one of claims 1-15, characterized in that, Mixing the water phase, the oil phase, the emulsifier, the catalyst and the dispersant, standing, and then solidifying to obtain the skin repair Janus film.

17. Use of a skin treatment Janus film according to any one of claims 1-15, characterized in that, A material for skin repair and / or promoting skin wound healing.

18. The use according to claim 17, characterized in that, The material for skin repair and / or promoting skin wound healing is a film material.

19. A cosmetic composition comprising the skin repair Janus film of any one of claims 1-15, and a cosmetically acceptable carrier.

20. The cosmetic composition of claim 19, wherein The cosmetic composition is selected from the group consisting of a facial mask, an eye mask, a lip mask, or a combination thereof.

21. A medical material comprising the skin repair Janus film of any one of claims 1-15.

22. The medical material according to claim 21, wherein The medical material is a skin wound dressing.

23. A metastable emulsion characterized in that, The metastable emulsion comprises an oil phase, a water phase and an emulsifier; The oil phase comprises an end-vinyl silicone oil and a low-viscosity silicone oil; the water phase comprises hyaluronic acid or its salt and water.

24. The metastable emulsion of claim 23, wherein, The metastable emulsion is prepared by a method comprising the following steps: The metastable emulsion is prepared by a method comprising the following steps: (1) mixing the oil phase with the emulsifier to obtain an oil phase system; (2) mixing water and hyaluronic acid or a salt thereof to obtain an aqueous phase; (3) mixing the oil phase system with the aqueous phase to obtain the meta-stable emulsion.

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