Water-in-oil emulsion composition having water-soluble active ingredients and preparation method therefor

Abstract

Provided is a water-in-oil emulsion composition. The composition comprises water-soluble active ingredients, fats and oils, emulsifiers, and water. Further provided is a preparation method for the composition. The composition has the characteristics of good transparency, high drug loading capacity, and / or a good transdermal effect.

Description

Water-soluble active ingredient-containing water-in-oil emulsion composition and preparation method thereof TECHNICAL FIELD

[0001] The present application belongs to the technical field of cosmetics, and particularly relates to a water-soluble active ingredient-containing water-in-oil emulsion composition. BACKGROUND

[0002] In recent years, the concept of "nourishing skin with oil" has emerged in the field of cosmetics. Pure oil systems have a unique skin feel, good moisturizing properties, and better absorption of active ingredients, and their share in skin care products has been increasing year by year. Currently, the active ingredients added to pure oil systems are mainly oil-soluble essential oils, oil-soluble spilanthes, frankincense resin, ganoderma triterpenes, teprenone, astaxanthin, etc. However, many cosmetic active ingredients are water-soluble, such as bovine growth factors, icodextrin, ergot alkaloids, hyaluronic acid, collagen, and peptides, etc. These water-soluble ingredients are difficult to add to pure oil systems and maintain good physicochemical properties of the system.

[0003] To solve this problem, the cosmetics industry usually puts oil and water into the same bottle, shakes them to form an unstable oil-water mixture before use, and then uses it. This method not only causes inconvenience to consumers, but also the uneven oil-water mixture may have inaccurate dosage of active ingredients. At the same time, the short-term formation of oil-water mixture is not conducive to the penetration of water-soluble active ingredients into the skin, making it difficult to exert the effect of active ingredients.

[0004] Emulsion refers to a non-uniformly dispersed liquid preparation formed by dispersing one phase in the form of small droplets in another phase. Emulsion can be generally divided into oil-in-water and water-in-oil types, and water-in-oil emulsion can encapsulate water-soluble active ingredients in the oil phase.

[0005] Emulsion with particle size in the range of 200-500 nm has a milky white appearance due to the large particle size of the internal phase. When added to oil, it can mask the color of the oil itself, making it difficult to bring joy to consumers, and therefore is not suitable for pure oil systems of water-soluble active ingredients.

[0006] Emulsions with particle sizes in the range of 10 nm to 200 nm are usually transparent or translucent, but this system is more commonly used in oil-in-water emulsions. In the paper "Microemulsions and Nanoemulsions in Skin Drug Delivery" by Sout EB et al., 24 active ingredients were prepared into emulsions for transdermal delivery of drugs, only one active ingredient used water-in-oil emulsion, and the water-in-oil emulsion usually has low drug content. The water-in-oil emulsion of asiaticoside reported in patent document CN113546016A has a content of only 0.2%. Cao YR et al. prepared a water-in-oil emulsion of teriflunomide in "Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide", which has a drug content of only 0.1% (Chem Pharm Bull (Tokyo). 2019; 67(8): 786-794). Liu Fang et al. prepared different specifications of fluorouracil water-in-oil emulsion in "Promoting the transdermal penetration of fluorouracil with water-in-oil microemulsion as carrier", which has a drug content of up to 0.5% (Acta Pharmaceutica Sinica 2009, 44(5): 540-547).

[0007] Therefore, it is technically difficult to develop a transparent or translucent water-in-oil emulsion with high drug loading.

[0008] SUMMARY

[0009] The present application relates to a water-in-oil emulsion composition, which has the characteristics of good transparency, high drug loading and / or good transdermal effect. The present application also provides a preparation method of the water-in-oil emulsion composition.

[0010] The first aspect of the present application relates to a water-in-oil emulsion composition, which comprises a water-soluble efficacy ingredient, an oil, an emulsifier and water;

[0011] The mass percentage of the water-soluble efficacy ingredient is 0.1% to 20%; the mass percentage of the oil is 30% to 90%; the mass percentage of the emulsifier is 1% to 30%; and the mass percentage of water is 1% to 20%;

[0012] The water-soluble efficacy ingredient is selected from one or more of the following: boswellic acid (CAS: 439685-79-7), ikarosine (CAS: 96702-03-3), and ergothioneine (CAS: 497-30-3).

[0013] The oil is selected from one or more of silicone oil, oil of plant origin, synthetic oil, and hydrocarbon-based oil.

[0014] The emulsifier is selected from polyethylene glycol (PEG) fatty acid ester and / or polyglyceryl fatty acid ester; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, polyhydroxystearic acid.

[0015] In some embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 1-20%. More preferably, the water-soluble efficacy ingredient is present in a mass percentage of 2-20%. Even more preferably, the water-soluble efficacy ingredient is present in a mass percentage of 5-20%. In some specific embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 5%, 10%, 15%, or 20%. In some specific embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 5%. In some specific embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 10%. In some specific embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 15%. In some specific embodiments, the water-soluble efficacy ingredient is present in a mass percentage of 20%.

[0016] In some embodiments, the oil is present in a mass percentage of 35-85%. Preferably, the oil is present in a mass percentage of 40-85%. More preferably, the oil is present in a mass percentage of 40-75%. In some specific embodiments, the oil is present in a mass percentage of 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75%. In some specific embodiments, the oil is present in a mass percentage of 40%. In some specific embodiments, the oil is present in a mass percentage of 65%. In some specific embodiments, the oil is present in a mass percentage of 70%. In some specific embodiments, the oil is present in a mass percentage of 75%.

[0017] In some embodiments, the emulsifier is present in a mass percentage of 1-25%. Preferably, the emulsifier is present in a mass percentage of 1-20%. More preferably, the emulsifier is present in a mass percentage of 5-20%. In some specific embodiments, the emulsifier is present in a mass percentage of 5%, 10%, 15%, or 20%. In some specific embodiments, the emulsifier is present in a mass percentage of 5%. In some specific embodiments, the emulsifier is present in a mass percentage of 10%. In some specific embodiments, the emulsifier is present in a mass percentage of 15%. In some specific embodiments, the emulsifier is present in a mass percentage of 20%.

[0018] In some embodiments, the water is present in an amount of 2-20% by mass. Preferably, the water is present in an amount of 3-20% by mass. More preferably, the water is present in an amount of 5-20% by mass. In some specific embodiments, the water is present in an amount of 5%, 10%, 15% or 20% by mass. In some specific embodiments, the water is present in an amount of 5% by mass. In some specific embodiments, the water is present in an amount of 10% by mass. In some specific embodiments, the water is present in an amount of 15% by mass. In some specific embodiments, the water is present in an amount of 20% by mass.

[0019] In some embodiments, the water-soluble efficacy ingredient is present in an amount of 1-20% by mass, the oil is present in an amount of 35-85% by mass, the emulsifier is present in an amount of 1-25% by mass, and the water is present in an amount of 2-20% by mass.

[0020] In some embodiments, the water-soluble efficacy ingredient is present in an amount of 2-20% by mass, the oil is present in an amount of 40-85% by mass, the emulsifier is present in an amount of 1-20% by mass, and the water is present in an amount of 3-20% by mass.

[0021] In some embodiments, the water-soluble efficacy ingredient is present in an amount of 5-20% by mass, the oil is present in an amount of 40-75% by mass, the emulsifier is present in an amount of 5-20% by mass, and the water is present in an amount of 5-20% by mass.

[0022] In some embodiments, the water-soluble efficacy ingredient is present in an amount of 5-20% by mass, the oil is present in an amount of 65-75% by mass, the emulsifier is present in an amount of 10-20% by mass, and the water is present in an amount of 5-20% by mass.

[0023] In some embodiments, the water-soluble efficacy ingredient is a boswellic acid.

[0024] In other embodiments, the water-soluble efficacy ingredient is an ektoxin.

[0025] In other embodiments, the water-soluble efficacy ingredient is an ergothioneine.

[0026] In other embodiments, the water-soluble efficacy ingredient is a mixture of any two or all of a boswellic acid, an ektoxin, and an ergothioneine.

[0027] In some embodiments, the silicone oil is selected from one or more of polydimethylsiloxane, polydimethylsiloxane alcohol, cyclopentasiloxane, cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, cycloheptasiloxane, decamethylcyclopentasiloxane, cyclotetrasiloxane, cyclotrisiloxane, octyl dimethicone, octyl trimethicone, octyl methicone, cetyl methicone, cetyl methicone, hexyl methicone, lauryl methicone, myristyl methicone, phenyl methicone, stearyl methicone, stearyl dimethicone, behenyl dimethicone, trifluoropropyl methicone, cetyl dimethicone, phenyl methicone, dimethyl polysiloxane, methyl phenyl polysiloxane, methyl trimethylsiloxane, diphenylsiloxy, phenyl trimethylsiloxane, phenyl trimethylsiloxane.

[0028] Preferably, the silicone oil is selected from one or more of polydimethylsiloxane, polydimethylsiloxane alcohol, cyclomethicone.

[0029] In some embodiments, the plant-derived oil is selected from one or more of white pool flower seed oil, castor seed oil, olive oil, peanut oil, corn oil, cottonseed oil, coconut oil, palm oil, palm kernel oil, sesame oil, soybean oil, almond oil, sweet apricot kernel oil, wheat germ oil, safflower oil, oat kernel oil, avocado oil, macadamia seed oil, evening primrose oil, rice bran oil, stone oil, oil tea seed oil, camellia seed oil, behenyl oil, rosemary oil, rice bran oil, sea buckthorn oil, water garlic seed oil, linseed oil, borage seed oil, jojoba seed oil, cocoa seed oil.

[0030] Preferably, the plant-derived oil is selected from one or more of soybean oil, camellia seed oil, white pool flower seed oil, jojoba seed oil.

[0031] In some embodiments, the synthetic oil is selected from one or more of caprylic acid triglyceride, capric acid triglyceride, stearic acid triglyceride, oleic acid triglyceride, lauric acid triglyceride, myristic acid triglyceride.

[0032] Preferably, the synthetic oil is selected from one or more of oleic acid triglyceride, caprylic acid triglyceride, capric acid triglyceride.

[0033] In some embodiments, the hydrocarbon oil is selected from one or more of squalane, isooctane, isododecane, isohexadecane, isoeicosane, C 10 ~ C 13 isododecane, C 12 ~ C 14 isododecane.

[0034] Preferably, the hydrocarbon oil is squalane.

[0035] In some embodiments, the polyethylene glycol (PEG) fatty acid ester is a polyethylene glycol (PEG) di-fatty acid ester having a degree of polymerization of 2 to 30; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxystearic acid;

[0036] Preferably, the polyethylene glycol (PEG) fatty acid ester is selected from one or more of PEG-3 distearate, PEG-3 dipalmitate, PEG-4 distearate, PEG-4 dioleate, PEG-6 distearate, PEG-6 diisostearate, PEG-6 dilaureate, PEG-8 distearate, PEG-8 dilaureate, PEG-8 diisostearate, PEG-8 dioleate, PEG-9 distearate, PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, and PEG-30-dipolyhydroxystearate;

[0037] More preferably, the polyethylene glycol (PEG) fatty acid ester is selected from one or more of PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, and PEG-30-dipolyhydroxystearate.

[0038] In some embodiments, the polyglyceryl fatty acid ester is a polyglyceryl di-fatty acid ester having a degree of polymerization of 2 to 10; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxystearic acid;

[0039] Preferably, the polyglyceryl fatty acid ester is a polyglyceryl di-fatty acid ester having a degree of polymerization of 2 to 10; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxystearic acid;

[0040] More preferably, the polyglyceryl fatty acid ester is selected from one or more of polyglyceryl-2 dioleate, polyglyceryl-2 distearate, polyglyceryl-3 distearate, polyglyceryl-3 diisostearate, polyglyceryl-4 dilaureate, polyglyceryl-6 dioleate, polyglyceryl-6 distearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate;

[0041] More preferably, the polyglyceryl fatty acid ester is selected from one or more of polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate.

[0042] In some embodiments, the emulsifier is selected from one or more of PEG-3 distearate, PEG-3 dipalmitate, PEG-4 distearate, PEG-4 dioleate, PEG-6 distearate, PEG-6 diisostearate, PEG-6 dilaurate, PEG-8 distearate, PEG-8 dilaurate, PEG-8 diisostearate, PEG-8 dioleate, PEG-9 distearate, PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaurate, PEG-30-dipolyhydroxystearate, polyglyceryl-2 dioleate, polyglyceryl-2 distearate, polyglyceryl-3 distearate, polyglyceryl-3 diisostearate, polyglyceryl-4 dilaurate, polyglyceryl-6 dioleate, polyglyceryl-6 distearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaurate, and polyglyceryl-10 dioleate.

[0043] Preferably, the emulsifier is selected from one or more of PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaurate, PEG-30-dipolyhydroxystearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaurate, and polyglyceryl-10 dioleate.

[0044] In particular, in some embodiments, the emulsifier is PEG-12 dioleate.

[0045] In particular, in some embodiments, the emulsifier is PEG-30-dipolyhydroxystearate.

[0046] In particular, in some embodiments, the emulsifier is polyglyceryl-10 distearate.

[0047] A second aspect of the present application relates to a method for preparing the aforementioned water-in-oil emulsion composition, the method comprising the steps of:

[0048] (1) dissolving an emulsifier into oil to form an oil phase; dissolving a water-soluble efficacy ingredient into water to form a water phase;

[0049] (2) slowly adding the water phase into the oil phase under stirring, and continuing to stir to obtain a transparent water-in-oil emulsion composition.

[0050] In the composition, the mass percentage of the water-soluble efficacy ingredient is 0.1%-20%; the mass percentage of the oil is 30-90%; the mass percentage of the emulsifier is 1-30%; and the mass percentage of the water is 1%-20%.

[0051] The present application brings one or more of the following technical effects:

[0052] 1. The drug loading of the water-in-oil emulsion reported in the prior art is low, which cannot meet the addition amount requirement of water-soluble functional ingredients in cosmetics. The water-in-oil emulsion composition provided by the present application can improve the drug loading of water-soluble functional ingredients, and the addition amount of water-soluble functional ingredients can reach 20%, which can meet the development requirements of both low drug loading and high drug loading types of cosmetics.

[0053] 2. With the increase of the addition amount of water-soluble functional ingredients, the emulsion system may be unstable, and may easily produce unemulsion, demulsification and crystal precipitation. The present application accidentally obtains some emulsifiers through screening tests, and by adding these emulsifiers, the water-in-oil emulsion composition of the present application can obtain system stability and good transparency even in the case of high drug loading.

[0054] 3. The water-in-oil emulsion composition provided by the present application has a simple preparation process, and is prepared by simple stirring at room temperature, which is easy to industrialize.

[0055] 4. The water-in-oil emulsion composition provided by the present application has excellent transdermal effect.

[0056] The details of the application are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, illustrative methods and materials are described herein, and it is to be understood that like or equivalent methods and materials can be used in accordance with the teachings and practices of the present application, and the purposes and advantages of the present application will be apparent from the specification and claims, according to the specification and claims of the present application. In the specification and the appended claims, the singular form also includes the plural form, unless the context clearly dictates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present application belongs. All patents and publications cited in the specification are incorporated herein by reference in their entirety.

[0057] The contents of all references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated by reference in their entirety. 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.

[0058] Drawings of the specification

[0059] Figure 1 is a particle size spectrum of the water-in-oil emulsion composition measured in Example 2.

[0060] Figure 2 is a schematic diagram of water-in-oil emulsifiers with single-chain and double-chain structures.

[0061] Figure 3 is a photograph showing the complete transparent or substantially transparent effect of the water-in-oil emulsion of the present application. DETAILED DESCRIPTION

[0062] The technical solutions of the present application are further described below in combination with some specific examples, but these examples do not limit the scope of the present application.

[0063] Preparation of a water-in-oil emulsion composition of Example 1

[0064] Preparation of a water-in-oil emulsion composition containing bovine growth factors of Example 1A

[0065] (1) Preparation of the oil phase

[0066] Take a 100ml beaker and add 0.5g of polyglyceryl-3 distearate and 43.5g of caprylic / capric triglyceride, respectively, and stir until dissolved at room temperature to obtain the oil phase;

[0067] (2) Preparation of the water phase

[0068] Take a 10ml centrifuge tube and add 1g of bovine growth factors and 5g of pure water, respectively, and ultrasonically dissolve to obtain the water phase;

[0069] (3) Preparation of the water-in-oil emulsion of the water-soluble active ingredient

[0070] Under magnetic stirring at 100rpm / min, add the water phase to the oil phase, and stir for 10min until the solution is clear and transparent to obtain a 2% bovine growth factor water-in-oil emulsion composition.

[0071] Preparation of a water-in-oil emulsion composition containing icodextrin of Example 1B

[0072] (1) Preparation of the oil phase

[0073] Take a 100ml beaker and add 1g of PEG-12 distearate and 43g of caprylic / capric triglyceride, respectively, and stir until dissolved at room temperature to obtain the oil phase;

[0074] (2) Preparation of the water phase

[0075] Take a 10ml centrifuge tube and add 1g of icodextrin and 5g of pure water, respectively, and ultrasonically dissolve to obtain the water phase;

[0076] (3) Preparation of the water-in-oil emulsion of the water-soluble active ingredient

[0077] Under magnetic stirring at 100rpm / min, add the water phase to the oil phase, and stir for 10min until the solution is clear and transparent to obtain a 2% icodextrin water-in-oil emulsion composition.

[0078] Preparation of a water-in-oil emulsion composition containing ergothioneine of Example 1C

[0079] (1) Preparation of oil phase

[0080] Take 100ml beaker, respectively, add 1.5g PEG-12 laurate, 42.5g caprylic / capric acid triglyceride, stirring at room temperature until dissolved evenly, namely oil phase;

[0081] (2) Preparation of water phase

[0082] Take 10ml centrifuge tube, respectively, add 1g ergothioneine, 5g pure water, ultrasonic dissolution, namely water phase;

[0083] (3) Preparation of water-soluble active ingredient water-in-oil emulsion

[0084] Under the use of 100rpm / min magnetic stirring, add water phase to oil phase, stir for 10min until the solution is clear and transparent, namely 2% ergothioneine water-in-oil emulsion composition.

[0085] Example 2 Particle size determination of water-in-oil emulsion composition

[0086] This example provides a particle size determination method of water-soluble active ingredient water-in-oil emulsion composition. The particle size determination method is shown as follows:

[0087] Take 20μL of 2% ergothioneine water-in-oil emulsion prepared in Example 1A and dissolve it in 1mL of caprylic / capric acid triglyceride. Use Malvern nanoparticle size determination instrument (Zetasizer Pro) to determine the sample. The particle size spectrum is shown in Figure 1. Figure 1 shows that the average particle size of 2% ergothioneine water-in-oil emulsion is 69nm.

[0088] Example 3 Effect of different types of emulsifiers on the stability of water-soluble active ingredient water-in-oil emulsion composition

[0089] When preparing water-soluble active ingredient water-in-oil emulsion, emulsifier is the key factor to form water-in-oil emulsion. Generally speaking, the hydrophilic-lipophilic balance value (HLB) of the emulsifier that can form water-in-oil emulsion is generally 3-8, and these emulsifiers can be divided into different types of emulsifiers based on the nature of the hydrophilic group, such as nonionic emulsifiers, cationic emulsifiers, anionic emulsifiers. The emulsifier used in general cosmetics is mainly nonionic emulsifier, the main reason is that nonionic emulsifier can tolerate a wider pH range and is not affected by electrolytes.

[0090] The purpose of this example is to investigate the effect of different types of nonionic emulsifiers on the stability of water-soluble active ingredient water-in-oil emulsion.

[0091] The preparation method of each formula in this example is referred to Example 1.

[0092] Investigation method: the appearance of each formula was observed and recorded. The results are shown in Table 1.

[0093] Table 1 Influence of different types of non-ionic emulsifiers on the stability of water-soluble functional ingredient-containing water-in-oil emulsion

[0094] As shown in Table 1, Formula 3.4 and Formula 3.5 used emulsifiers with double-chain structure to prepare emulsions; while Formula 3.1-3.3 and 3.6-3.8 used emulsifiers with single-chain structure, and all failed to prepare emulsions. This example tried different types of non-ionic emulsifiers, and unexpectedly found that water-in-oil emulsifiers with straight-chain structure were difficult to form water-in-oil emulsion, while water-in-oil emulsifiers with double-chain structure (Figure 2) could form water-in-oil emulsion. It is speculated that the water-soluble active substances in the water phase may disturb the oil-water interface, resulting in unstable water-in-oil emulsion, while the double-chain structure can more firmly stabilize the oil-water interface.

[0095] Example 4 Influence of different double-chain structure emulsifiers on bovine serum albumin water-in-oil emulsion

[0096] This example further investigates the influence of different types and lengths of hydrophilic-lipophilic double-chain emulsifiers on water-in-oil emulsion. In this example, the preparation method of each formula is referred to Example 1, and the particle size determination method is referred to Example 2.

[0097] Table 2 Influence of different double-chain structure emulsifiers on bovine serum albumin water-in-oil emulsion

[0098] The results in Table 2 show that the longer the hydrophilic end of the emulsifier, the smaller the particle size of the emulsion formed, and the higher the transparency of the emulsion. It is speculated that the longer the hydrophilic end, the thicker the hydration layer formed, which can prevent the active substances in the inner water phase from approaching the oil-water interface, thus reducing the disturbance to the oil-water interface.

[0099] Example 5 Formula screening of bovine serum albumin water-in-oil emulsion with different concentrations

[0100] In order to improve the drug loading capacity of water-in-oil emulsion while ensuring the transparency of the emulsion, this example comprehensively screens the amount of PEG-12 distearate, PEG-30-dipolyhydroxystearate, and polyglyceryl-10 distearate, etc. The specific results are shown in Table 3, Table 4, and Table 5. The preparation method of each formula is referred to Example 1.

[0101] Table 3 Influence of PEG-12 distearate on bovine serum albumin water-in-oil emulsion with different concentrations

[0102] Table 4 Effect of PEG-30-dihydroxystearate on water-in-oil emulsions with different concentrations of bovine collagen

[0103] Table 5 Effect of polyglyceryl-10 distearate on water-in-oil emulsions with different concentrations of bovine collagen

[0104] As can be seen from Tables 3, 4 and 5, when PEG-12 distearate, PEG-30- dihydroxystearate and polyglyceryl-10 distearate are used as emulsifiers, the emulsions with bovine collagen content of 20% or less have good transparency. Among the three emulsifiers, PEG-30-dihydroxystearate has the best emulsifying effect. When the bovine collagen content is in the range of 5%-20%, 5%-30% PEG-30-dihydroxystearate can achieve complete transparency or substantially transparent effect (Figure 3).

[0105] Example 6 Adaptability of PEG-30-dihydroxystearate in different oils

[0106] This example investigates the effect of various different oils on the appearance of emulsions when PEG-30-dihydroxystearate is used as an emulsifier. The preparation method of each formula is as described in Example 1. The specific results are shown in Table 6.

[0107] Table 6 Transparency of PEG-30-dihydroxystearate in different oils

[0108] As can be seen from Table 6, the emulsions prepared from various formulas all have substantially transparent or completely transparent effect, which shows that PEG-30-dihydroxystearate has good adaptability to various typical oils.

[0109] Example 7 Preparation of high-concentration water-in-oil emulsions of ergothioneine and icodextrin

[0110] This example investigates the adaptability of other water-soluble active ingredients (such as ergothioneine and icodextrin) to high-concentration water-in-oil emulsion systems. The preparation method of each formula is as described in Example 1. The specific results are shown in Table 7.

[0111] Table 7 Formulas of high-concentration water-in-oil emulsions of ergothioneine and icodextrin

[0112] As can be seen from Table 7, other water-soluble active ingredients (such as ergothioneine and icodextrin) also have good transparency when the water-in-oil emulsion formula of the present application is used to prepare emulsions. This shows that the water-in-oil emulsion formula of the present application has good adaptability to other water-soluble active ingredients.

[0113] Example 8 Stability investigation of high drug loading water-in-oil emulsion

[0114] This example investigates the stability of water-in-oil emulsions of different proportions of boswelia, ectoin and ergothioneine with PEG-30-dipolyhydroxystearate as emulsifier at 2-8℃, 25±2℃ and 40±2℃. The preparation method of each emulsion is according to Example 1.

[0115] Table 8 Stability investigation of water-in-oil emulsions of boswelia, ectoin and ergothioneine at 2-8℃

[0116] Table 9 Stability investigation of water-in-oil emulsions of boswelia, ectoin and ergothioneine at 25±2℃

[0117] Table 10 Stability investigation of water-in-oil emulsions of boswelia, ectoin and ergothioneine at 40±2℃

[0118] From Table 8, Table 9 and Table 10, it can be seen that the particle size and appearance of each emulsion composition with different proportions did not change significantly after being placed at 2-8℃, 25±2℃ and 40±2℃ for 1 week, and still maintained a transparent or translucent state, with good stability. Among them, at 40±2℃, the particle size of the emulsion composition increased slightly, but its appearance hardly changed, and still maintained a transparent state.

[0119] Example 9 Investigation of transdermal performance of high drug loading water-in-oil emulsion of boswelia

[0120] Boswelia is a polyhydroxy alcohol compound, and its target site is located in the dermis. Boswelia can fill the gap of extracellular matrix (ECM) by stimulating the production of glycosaminoglycans (GAGs) and increasing the water content between the extracellular matrix, so as to reduce wrinkles in the skin. However, the molecular polarity of boswelia is high, which makes it difficult to penetrate the lipophilic stratum corneum. At present, boswelia is widely used in cosmetics such as face cream. Among them, the most famous is the "black tape series" cream of L'Oreal Company. In terms of resident cosmetics containing active ingredients, the transdermal performance of the active ingredients in the product becomes the key to its effect.

[0121] The commercially available "Black Tape Series" cream (containing 10% of bovine collagen) was used as a positive control, and the 2% bovine collagen water-in-oil emulsion (formula 3.1 in Table 1), the 2% bovine collagen water-in-oil emulsion (formula 3.2 in Table 1), the 2% bovine collagen water-in-oil emulsion (formula 3.3 in Table 1), the 2% bovine collagen water-in-oil emulsion (formula 3.4 in Table 1), the 2% bovine collagen water-in-oil emulsion (formula 3.5 in Table 1), the 5% bovine collagen water-in-oil emulsion (formula 6.9 in Table 6), the 10% bovine collagen water-in-oil emulsion (formula 8.3 in Table 8), and the 20% bovine collagen water-in-oil emulsion (formula 8.7 in Table 8) prepared in the foregoing examples were used as test samples, and the penetration of bovine collagen in the test samples and the positive control was studied using a Franz Cell diffusion cell penetration experiment.

[0122] The operation was as follows: The abdomen of a miniature pig was fixed between the supply pool and the receiving pool of a TK-24II transdermal test system, and about 8 ml of physiological saline was added to the receiving pool to exhaust the air, so that the dermal layer of the skin was in close contact with the receiving liquid. Then, 0.2 g of the test sample (the layered emulsion of formula 3.1, 3.2, and 3.3 was used after shaking) was added to the surface of the skin, and a plastic spatula was used to evenly spread the sample from the center of the skin to the edge. There were 6 parallel samples for each sample, and a constant temperature water bath at 32±0.5°C was used for incubation at a speed of 200 rpm / min. After 24 h of incubation, the skin was taken out of the diffusion cell, the preparation was scraped off, and the effective skin area of 3.14 cm 2 The skin was washed with pure water, dried, and the surface residues were removed by adhesive tape. The skin was weighed, cut into small particles, and placed in a 2 mL grinding tube. 1 mL of 80% acetonitrile was added for homogenization extraction, and the mixture was centrifuged at 12000 rpm for 5 min at 4°C. The supernatant was injected into the HPLC for analysis, and the results are shown in the following table.

[0123] Table 11: Results of bovine collagen intradermal retention amount determination (n=6)

[0124] As can be seen from Table 11, after 24 h of in vitro penetration experiment, compared with formula 3.1-3.3, formula 3.4 and formula 3.5 showed higher intradermal bovine collagen retention amount, which indicated that formula 3.4 and formula 3.5 could improve the transdermal absorption performance of active ingredients such as bovine collagen; compared with the positive control, the intradermal bovine collagen retention amount of the bovine collagen water-in-oil emulsion of formula 8.3 was 3.5 times that of the positive control, which was significantly higher than that of the positive control; the intradermal bovine collagen retention amount of the bovine collagen water-in-oil emulsion of formula 6.9 and formula 8.7 was also higher than that of the positive control; therefore, the water-in-oil emulsion of the present application can improve the transdermal absorption performance of active ingredients such as bovine collagen.

[0125] It is to be understood that while the above-identified patent application has been chosen for illustration, that this application can have many modifications and changes of form and further constitutes useful embodiments falling within the scope of the appended claims.

Claims

1. A water-in-oil emulsion composition characterized in that, The composition comprises a water-soluble efficacy ingredient, oil, emulsifier and water; wherein the mass percentage of the water-soluble efficacy ingredient is 0.1%-20%; the mass percentage of the oil is 30-90%; the mass percentage of the emulsifier is 1-30%; the mass percentage of the water is 1%-20%; The water-soluble efficacy ingredient is selected from one or more of the following: boswelia, ikkonia, ergothioneine; The oil is selected from one or more of the following: silicone oil, oil from plant source, synthetic oil and hydrocarbon oil; The emulsifier is selected from polyethylene glycol fatty acid ester and / or polyglycerin fatty acid ester; The fatty acid is selected from one or more of the following: stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, polyhydroxy stearic acid.

2. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 1%-20%; preferably, the mass percentage of the water-soluble efficacy ingredient is 2%-20%; more preferably, the mass percentage of the water-soluble efficacy ingredient is 5%-20%.

3. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 5%, 10%, 15% or 20%.

4. The composition of claim 1, wherein, The mass percentage of the oil is 35-85%; preferably, the mass percentage of the oil is 40-85%; more preferably, the mass percentage of the oil is 40-75%.

5. The composition of claim 1, wherein, The mass percentage of the oil is 40%, 45%, 50%, 55%, 60%, 65%, 70% or 75%.

6. The composition of claim 1, wherein, The mass percentage of the emulsifier is 1-25%; preferably, the mass percentage of the emulsifier is 1-20%; more preferably, the mass percentage of the emulsifier is 5-20%.

7. The composition of claim 1, wherein, The mass percentage of the emulsifier is 5%, 10%, 15% or 20%.

8. The composition of claim 1, wherein, The mass percentage of the water is 2%-20%; preferably, the mass percentage of the water is 3%-20%; more preferably, the mass percentage of the water is 5%-20%.

9. The composition of claim 1, wherein, The mass percentage of the water is 5%, 10%, 15% or 20%.

10. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 1%-20%, the mass percentage of the oil is 35-85%, the mass percentage of the emulsifier is 1-25%, and the mass percentage of the water is 2%-20%.

11. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 2%-20%, the mass percentage of the oil is 40-85%, the mass percentage of the emulsifier is 1-20%, and the mass percentage of the water is 3%-20%.

12. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 5%-20%, the mass percentage of the oil is 40-75%, the mass percentage of the emulsifier is 5-20%, and the mass percentage of the water is 5%-20%.

13. The composition of claim 1, wherein, The mass percentage of the water-soluble efficacy ingredient is 5%-20%, the mass percentage of the oil is 65-75%, the mass percentage of the emulsifier is 10-20%, and the mass percentage of the water is 5%-20%.

14. The composition according to any one of claims 1 to 13, characterized in that, The water-soluble efficacy ingredient is boswelia.

15. The composition according to any one of claims 1 to 13, characterized in that, The water-soluble efficacy ingredient is ikkonia.

16. The composition according to any one of claims 1 to 13, characterized in that, The water-soluble efficacy ingredient is ergothioneine.

17. The composition according to any one of claims 1-13, wherein, The water-soluble efficacy ingredient is a mixture of any two of the following: boswellic acid, ecdysterone, and ergothioneine, or a mixture of all three.

18. The composition according to any one of claims 1-13, wherein, The silicone oil is selected from one or more of the following: dimethicone, dimethiconol, cyclopentasiloxane, cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, cycloheptasiloxane, decamethylcyclopentasiloxane, cyclotetrasiloxane, cyclotrisiloxane, octyl dimethicone, octyl trimethylsiloxysilicate, octyl trimethylsiloxysilicate, cetyl stearyl trimethylsiloxysilicate, cetyl trimethylsiloxysilicate, hexyl trimethylsiloxysilicate, lauryl trimethylsiloxysilicate, myristyl trimethylsiloxysilicate, phenyl trimethylsiloxysilicate, stearyl trimethylsiloxysilicate, stearyl dimethicone, behenyl dimethicone, trifluoropropyl trimethylsiloxysilicate, cetyl dimethicone, phenyl methicone, dimethylpolysiloxane, methylphenylpolysiloxane, methyltrimethylsiloxysilicate, diphenylsilyloxyphenyl trimethylsiloxysilicate, and phenyl trimethylsiloxysilicate. Preferably, the silicone oil is selected from one or more of the following: dimethicone, dimethiconol, and cyclomethicone.

19. The composition according to any one of claims 1-13, wherein, The plant-derived oil is selected from one or more of the following: white pool flower seed oil, castor seed oil, olive oil, peanut oil, corn oil, cottonseed oil, coconut oil, palm oil, palm kernel oil, sesame oil, soybean oil, almond oil, sweet apricot kernel oil, wheat germ oil, safflower oil, oat kernel oil, avocado oil, macadamia seed oil, evening primrose oil, rice bran oil, stone oil, oil tea seed oil, camellia seed oil, behenyl oil, rosemary oil, rice bran oil, sea buckthorn oil, water garlic seed oil, linseed oil, glass seed oil, jojoba seed oil, and cocoa seed oil. Preferably, the plant-derived oil is selected from one or more of the following: soybean oil, camellia seed oil, white pool flower seed oil, and jojoba seed oil.

20. The composition of any one of claims 1-13, wherein, The synthetic oil is selected from one or more of the following: caprylic acid triglyceride, capric acid triglyceride, stearic acid triglyceride, oleic acid triglyceride, lauric acid triglyceride, and myristic acid triglyceride. Preferably, the synthetic oil is selected from one or more of the following: oleic acid triglyceride, caprylic acid triglyceride, and capric acid triglyceride.

21. The composition of any one of claims 1-13, wherein, The hydrocarbon oil is selected from the group consisting of squalane, isooctane, isododecane, isohexadecane, isoeicosane, C 10 ~C 13 isododecane, isohexadecane, isoeicosane, C 12 ~C 14 isododecane, isohexadecane, isoeicosane, C Preferably, the hydrocarbon oil is squalane.

22. The composition of any one of claims 1-13, wherein, The polyethylene glycol fatty acid ester is a polyethylene glycol difatty acid ester with a degree of polymerization of 2 to 30; the fatty acid is selected from one or more of the following: stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxystearic acid. Preferably, the polyethylene glycol fatty acid ester is selected from one or more of the following: PEG-3 distearate, PEG-3 dipalmitate, PEG-4 distearate, PEG-4 dioleate, PEG-6 distearate, PEG-6 diisostearate, PEG-6 dilaureate, PEG-8 distearate, PEG-8 dilaureate, PEG-8 diisostearate, PEG-8 dioleate, PEG-9 distearate, PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, and PEG-30-dipolyhydroxystearate. More preferably, the polyethylene glycol fatty acid ester is selected from one or more of PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, and PEG-30-dipolyhydroxy stearate.

23. The composition of any one of claims 1-13, wherein, The polyglyceryl fatty acid ester is a polyglyceryl di-fatty acid ester having a degree of polymerization of 2 to 10; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxy stearic acid; Preferably, the polyglyceryl fatty acid ester is a polyglyceryl di-fatty acid ester having a degree of polymerization of 2 to 10; the fatty acid is selected from one or more of stearic acid, palmitic acid, oleic acid, isostearic acid, lauric acid, and polyhydroxy stearic acid; More preferably, the polyglyceryl fatty acid ester is selected from one or more of polyglyceryl-2 dioleate, polyglyceryl-2 distearate, polyglyceryl-3 distearate, polyglyceryl-3 diisostearate, polyglyceryl-4 dilaureate, polyglyceryl-6 dioleate, polyglyceryl-6 distearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate. More preferably, the polyglyceryl fatty acid ester is selected from one or more of polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate.

24. The composition of any one of claims 1-13, wherein, The emulsifier is selected from one or more of PEG-3 distearate, PEG-3 dipalmitate, PEG-4 distearate, PEG-4 dioleate, PEG-6 distearate, PEG-6 diisostearate, PEG-6 dilaureate, PEG-8 distearate, PEG-8 dilaureate, PEG-8 diisostearate, PEG-8 dioleate, PEG-9 distearate, PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, PEG-30-dipolyhydroxy stearate, polyglyceryl-2 dioleate, polyglyceryl-2 distearate, polyglyceryl-3 distearate, polyglyceryl-3 diisostearate, polyglyceryl-4 dilaureate, polyglyceryl-6 dioleate, polyglyceryl-6 distearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate. Preferably, the emulsifier is selected from one or more of PEG-12 distearate, PEG-12 dioleate, PEG-12 dilaureate, PEG-30-dipolyhydroxy stearate, polyglyceryl-10 distearate, polyglyceryl-10 dipalmitate, polyglyceryl-10 dimyristate, polyglyceryl-10 dilaureate, and polyglyceryl-10 dioleate.

25. The composition of any one of claims 1-13, wherein, The emulsifier is PEG-12 dioleate.

26. The composition of any one of claims 1-13, wherein, The emulsifier is PEG-30-dipolyhydroxy stearate.

27. The composition of any one of claims 1-13, wherein, The emulsifier is polyglyceryl-10 distearate.

28. A method for preparing the water-in-oil emulsion composition according to any one of claims 1 to 27, comprising the steps of: (1) dissolving an emulsifier in a fat to form an oil phase; dissolving a water-soluble active ingredient in water to form an aqueous phase; (2) slowly adding the aqueous phase to the oil phase under stirring, and continuing to stir to obtain a transparent water-in-oil emulsion composition.

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