CN112120964A

CN112120964A - Water-in-water compositions with high levels of active agents

Info

Publication number: CN112120964A
Application number: CN201910556212.0A
Authority: CN
Inventors: 倪向梅; 丛远华; 冯春波; 乔小玲; 曹平
Original assignee: Shanghai Jahwa United Co Ltd
Current assignee: Shanghai Jahwa United Co Ltd
Priority date: 2019-06-25
Filing date: 2019-06-25
Publication date: 2020-12-25
Anticipated expiration: 2039-06-25
Also published as: CN112120964B

Abstract

The invention discloses a water-in-water composition bearing high-content active agents, which comprises the following components in percentage by weight: an internal phase comprising a polyol polymer having a molecular weight in the range of 200 to 600g/mol and an active agent, wherein the weight ratio of the polyol polymer to the active agent is equal to or greater than 9:1 and the polyol polymer in the internal phase is present in an amount of less than 55 weight percent based on the total weight of the compositionAmount%, active agent content up to 5% by weight, an external phase comprising a molecular weight in the range of 2 x 10⁵To 5X 10⁵g/mol of natural high molecular weight polysaccharide polymer, wherein the content of the external phase is 1 to 10 weight percent based on the total weight of the composition.

Description

Water-in-water compositions with high levels of active agents

Technical Field

The invention belongs to the technical field of cosmetics, and particularly relates to a water-in-water composition capable of bearing a high-content active agent and a preparation method thereof.

Background

Salicylic acid (also known as Salicylic acid, SA) is also known as Salicylic acid, a white crystalline powder that is found in natural willow bark, poplar leaves, and sweet birch. The molecular formula is C₇H₆O₃The structural formula is shown in figure 1. Salicylic acid was also known as "salicylic acid" because it was first extracted from willow bark.

Formula 1: structural formula of salicylic acid

Salicylic acid, as a phytohormone, has important physiological effects in the general plant body, such as: promoting plant rooting, inhibiting ethylene biosynthesis, delaying fruit after-ripening and aging, regulating plant photoperiod, inducing flowering, regulating seed germination and pore closure, and improving disease resistance. The salicylic acid is mainly used for clinically treating skin superficial mycosis, seborrheic dermatitis and the like, and the main dosage form in the medicinal field is ointment, and the upper limit of use is 5%.

Salicylic acid has been used relatively late in the cosmetic field, and its skin-care efficacy was mentioned in published papers by Kligman physicians in the american journal of skin surgery in 1997, before really beginning to be used on a large scale in skin care products. Salicylic acid is a fat-soluble organic acid, can go deep into the pore depth through the mode of fusing with sebum, and the keratotic plug, blackhead, the white head arch that block up the pore are loosened and floated out, play the effect of mediation pore, and after the pore was mediation, the sebum of skin secretion can be discharged in vitro on the one hand, and the food of bacterium reduces, and on the other hand makes most anaerobic bacteria that cause the acne disappear by oneself because of the entering of oxygen, reaches the effect of acne removal. In addition, salicylic acid can also dissolve the constitutional substances between cutins to make the cutin layer fall off, thereby removing the cutin layer accumulated too thickly and promoting skin metabolism, and thus it is also often used in whitening products.

However, salicylic acid is relatively irritating, easily irritates skin and mucous membranes, can react with proteins in body tissues, easily causes skin allergy, is not tolerant to relatively dry and sensitive skin, and therefore cannot be used in a high concentration in skin care products. The cosmetic hygiene code (2007 edition) stipulates that the limited amount of salicylic acid in resident products is 2.0%; the limit amount in rinsing and hair products is 3.0%.

Salicylic acid has good lipid solubility, is easily dissolved in organic solvents such as ethanol and the like, but has poor water solubility and is easy to crystallize and precipitate, so that the application of the salicylic acid in aqueous and oil-in-water skin care products is limited to a certain extent. At present, the most common solution in the development of skin care products is to add ethanol as a solvent of salicylic acid, and the dosage of ethanol is often several times of that of the salicylic acid to prevent the salicylic acid from being separated out, so that the addition amount of the salicylic acid in the formula is low (usually 1-2%), and the addition of the ethanol increases the formula irritation to a certain extent.

In order to reduce the problem of skin irritation caused by salicylic acid, many new technical and application studies have been made in recent years. In the literature, "salicylic acid-loaded N-hexadecanoyl-L-histidine hydrogel drug sustained release research", Lianglian et al have studied that a hydrogel system is used as a drug carrier, the characteristics that proteins and cells are not easily adhered to the surface of the hydrogel and the hydrogel has good biocompatibility are utilized to synthesize N-hexadecanoyl-L-histidine, the N-hexadecanoyl-L-histidine and salicylic acid dissolved in a mixed solvent of ethanol and water (volume ratio of 1: 1) in advance are prepared into hydrogel, and the sustained release of the salicylic acid is realized by controlling conditions of pH, temperature and the like. In the literature, "research on solid lipid nanoparticles as salicylic acid transdermal drug delivery carriers", Wang Effer et al research that salicylic acid is prepared into a solid lipid nanoparticle transdermal carrier system, improves the bioavailability of salicylic acid, increases the local reserve of salicylic acid, and obtains a stable blood concentration for a certain time through the slow release characteristic, thereby improving the treatment efficacy and the compliance of patients. However, the salicylic acid bearing system prepared by the above and similar methods has the disadvantages of complicated preparation steps, high process control requirements and high production cost.

The water-in-water technology is a similar emulsification system obtained by mixing two hydrophilic media under a certain condition to realize internal and external phase separation, and is different from the traditional oil-in-water or water-in-oil system, and the dispersed phase and the continuous phase of the water-in-water composition are both hydrophilic media without oil components. The studies in the documents Water-in-Water emulsion crystals stabilized by cellulose nanocrystals and Particles transferred at the drop Interface in Water-in-Water Emulsions, published the use of an average molecular weight of 5X 10⁵Dextran (dextran) in g/mol and an average molecular weight of 2X 10⁵g/mol polyethylene oxide (PEO)]However, the polyethylene oxide used in the above documents is a powdery raw material having a large molecular weight and cannot dissolve salicylic acid as an internal phase, so that the water-in-water composition prepared by this method cannot support salicylic acid according to the present invention, and thus this technique has not been put to practical use.

The present inventors have surprisingly found that water-in-water compositions can be prepared using certain natural polymeric polysaccharide polymers (e.g. dextran) and certain polyol polymers (e.g. polyethylene glycol) and that the water-in-water compositions prepared are suitable for carrying salicylic acid, especially high levels of salicylic acid.

Disclosure of Invention

In one aspect, the present invention provides a water-in-water composition bearing a high level of active agent comprising:

an internal phase comprising a polyol polymer having a molecular weight in the range of 200 to 600g/mol and an active agent, wherein the weight ratio of the polyol polymer to the active agent is equal to or greater than 9:1, the polyol polymer is present in the internal phase in an amount of less than 55 wt%, and the active agent is present in an amount up to 5 wt%, based on the total weight of the composition,

an external phase comprising a molecular weight in the range of 2 x 10⁵To 5X 10⁵g/mol of natural polymersA polysaccharide polymer, wherein the content of the natural high molecular weight polysaccharide polymer is 1 to 10 wt% based on the total weight of the composition.

In a preferred embodiment, the polyol polymer employed in the internal phase is selected from one or more combinations of polyethylene glycol, polypropylene glycol, polybutylene glycol.

In a preferred embodiment, the polyol polymer is present in an amount of 40 to 45 weight percent, based on the total weight of the composition.

In a preferred embodiment, the natural high molecular weight polysaccharide polymer in the external phase is selected from: one or more of alpha-glucan, beta-glucan, agarose, chitin, pullulan, gelatinized starch and xanthan gum.

In a preferred embodiment, the polysaccharide polymer is present in an amount of 2 to 6 wt%, based on the total weight of the composition.

In a preferred embodiment, the active agent carried in the water-in-water composition of the invention is salicylic acid.

In a preferred embodiment, the internal phase further comprises a molecular weight greater than 1 × 10⁵g/mol of polymer.

In a more preferred embodiment, the molecular weight is greater than 1 × 10⁵The g/mol polymer is selected from: one or more combinations of polyoxyethylene, polyoxypropylene, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, polyol polymers, and other polyoxyethylene-polyoxypropylene block-containing polymers.

In another aspect, the present invention is also directed to a method of making a water-in-water composition carrying a high level of active agent, the method comprising the steps of:

a) dispersing natural high molecular polysaccharide polymer into acceptable carrier in cosmetic field to prepare external phase,

b) the active agent and the polyol polymer are mixed to produce an internal phase,

c) adding the inner phase prepared in step a) to the outer phase prepared in step b) under homogenization conditions and mixing to obtain the water-in-water composition.

In a preferred embodiment, the homogenization conditions are 5000 to 15000 rpm.

In a preferred embodiment, the water-in-water composition has an emulsion droplet size of 1 micron to 5 microns.

In yet another aspect, the present invention also relates to the use of the water-in-water composition in cosmetics.

Brief description of the drawings

FIG. 1 shows a photograph of a sample of the water-in-water composition prepared in example 35 stored at 25 ℃ (day 2) showing salicylic acid crystallizing out.

Fig. 2 shows a photograph of a sample of the water-in-water composition prepared in example 40 after being stored at 25 ℃ for 1 month.

FIG. 3 shows photographs of samples of the water-in-water composition prepared in example 31 after storage at 25 ℃ for 1 month.

Figure 4 shows a photomicrograph (initial) of the water-in-water composition prepared in example 35 showing significant crystallization. The microscope used was OLYMPUS BX53 at 40-fold magnification.

Fig. 5 shows a photomicrograph (day 2) of the water-in-water composition prepared in example 26, showing that the particle size of the water-in-water composition is large and sparse. The microscope used was OLYMPUS BX53 at 40-fold magnification.

FIG. 6 shows a photomicrograph (day 2) of the water-in-water composition prepared in example 31 showing the presence of a phase interface and an emulsified particle size of about 1-5 μm. The microscope used was OLYMPUS BX53 at 40-fold magnification.

Detailed Description

Unless defined otherwise, 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 invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described herein. For the purposes of the present invention, the following terms are defined below.

The term "about" as used herein refers to an amount, level, value, dimension, size, or amount that differs by up to 30%, 20%, or 10% as compared to the amount, level, value, dimension, size, or amount of a reference. The percentages used herein are by weight unless otherwise indicated.

Throughout the specification and claims, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The present invention is based on the following unexpected findings: using natural macromolecular polysaccharide polymers (e.g. having an average molecular weight of 2X 10)⁵～5×10⁵g/mol dextran) and polyol polymers (e.g., polyethylene glycol 400 or polypropylene glycol having an average molecular weight of 400 g/mol) can be prepared to provide stable water-in-water compositions. In the water-in-water compositions prepared in accordance with the present invention, the polyol polymer forms the internal phase and is capable of carrying an active agent (e.g., salicylic acid, particularly high levels of salicylic acid); the natural high molecular weight polysaccharide polymer forms an external phase, the presence of which avoids direct contact of the active agent of the internal phase (e.g. salicylic acid) with the skin, thereby avoiding irritation of the active agent (e.g. salicylic acid). Thus, the present inventors have attempted to use such water-in-water compositions to carry high levels of salicylic acid.

The inventors of the present application have also found that the higher the concentration of the natural high-molecular polysaccharide polymer in the water-in-water composition prepared in the present invention, the higher the viscosity of the external phase, and the better the stability of the obtained water-in-water composition. For example, the viscosity of the water-in-water composition can be as high as 2000-4000 mPas when the dextran concentration is 2 wt%. Alternatively, when the dextran concentration is increased to 6 wt%, the viscosity of the water-in-water composition may be further increased up to 6000-10000mPa · s.

The inventors of the present application have also found that it is preferable to control the concentration ratio of the internal phase and the external phase when preparing the water-in-water composition of the present invention. For example, when the concentration of the polyol polymer in the inner phase is low, the polyol polymer may be miscible with the natural high molecular weight polysaccharide polymer in the outer phase, and the water-in-water composition may not be formed. On the other hand, if the concentration of the internal phase polyol polymer is too high (e.g., greater than 55 wt%, or greater than 60 wt%), a stable water-in-water composition cannot be prepared.

The inventors of the present application have also found that increasing the molecular weight of the internal phase polyol polymer helps to further increase the stability of the water-in-water composition. For example, a small amount of a high molecular weight polymer (e.g., molecular weight greater than 1X 10) may be added to the internal phase⁵g/mol polymer) to adjust the molecular weight of the polyol polymer in the final internal phase.

The inventors of the present application have also found that the use of a high speed homogenization process (e.g., 5000 to 10000rpm homogenization) during the preparation of the water-in-water composition of the present invention allows for a reduction in the droplet size of the final water-in-water composition, thereby further improving the stability of the water-in-water composition.

The inventors of the present application have also found that in water-in-water compositions carrying salicylic acid, it is preferable to control the ratio of the inner phase polyol polymer and salicylic acid. For example, the ratio of the polyol polymer and the salicylic acid may be controlled to be 9:1 or more to avoid crystallization out of the salicylic acid.

Internal phase

In the water-in-water compositions of the present invention, the polyol polymer is used to form the internal phase. For example, polyethylene glycol, polypropylene glycol, polybutylene glycol, or combinations thereof may be used to prepare the internal phase of the water-in-water composition. Preferably, the polyol polymer used in the internal phase is a polyol polymer that is liquid at ordinary temperatures (e.g., a temperature of 25 ℃).

In a particular embodiment, polyethylene glycol may be used as the internal phase of the water-in-water compositions of the present invention. Examples of polyethylene glycol include, but are not limited to, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600. Polyethylene glycol 400 has a relatively low molecular weight, is liquid at normal temperature, and is a polyol solvent commonly used in cosmetics. Furthermore, salicylic acid can be dissolved in polyethylene glycol 400 to form the internal phase of the water-in-water composition.

In certain embodiments of the present invention, increasing the molecular weight of the internal phase polyol polymer helps to further increase the stability of the water-in-water composition. For example, small amounts of high molecular weight polymer may be added to the internal phase to adjust the molecular weight of the polyol polymer in the final internal phase. In particular embodiments, the high molecular weight polymer added to the internal phase is selected from: one or more combinations of polyethylene oxide, polypropylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, gelatin, polyol polymers, and other polymers containing polyoxyethylene-polypropylene oxide blocks. In particular embodiments, the high molecular weight polymer added to the internal phase may be polyethylene glycol 14M or a poloxamer.

In certain embodiments of the invention, the high molecular weight polymer added to the internal phase has a molecular weight greater than 1 x 10⁵g/mol, preferably greater than 5X 10⁵g/mol. For example, a molecular weight of about 6X 10 may be added⁵To improve the stability of the water-in-water composition. In certain embodiments of the invention, the high molecular weight polymer is added to the internal phase in an amount of about 1 to about 5 weight percent, preferably about 1 to about 3 weight percent, and more preferably about 2 to about 3 weight percent.

The inner phase constitutes the internal dispersed phase of the composition and comprises the polyol polymer and other optional ingredients that are soluble in the polyol polymer or intimately mixed with the polyol polymer. The dispersed phase inner phase is stabilized within the continuous phase outer phase as discrete domains, with a majority of the discrete domains preferably having a size of from about 0.2 microns to about 10 microns, more preferably from about 0.5 microns to about 5 microns, more preferably from about 0.75 microns to about 5 microns, and most preferably from about 1 micron to about 5 microns.

In certain embodiments of the present invention, the amount of polyol polymer in the water-in-water composition is from about 30% to about 55%, preferably from about 40% to about 50% by weight of the composition. In some embodiments, the amount of polyol polymer in the water-in-water composition is from about 40% to about 45% by weight of the composition. In other embodiments, the amount of polyol polymer in the water-in-water composition is from about 45% to about 50% by weight of the composition.

External phase

In the water-in-water composition of the present invention, a natural high molecular weight polysaccharide polymer is used to form an external phase.

In a specific embodiment, the natural high molecular weight polysaccharide polymer which can be used as the external phase is selected from: one or more of alpha-glucan, beta-glucan, agarose, chitin, pullulan, gelatinized starch and xanthan gum.

The glucan is a homotype polysaccharide which is composed of glucose as monosaccharide, and glucose units are connected by glycosidic bonds. Which can be further classified into α -glucan and β -glucan according to the type of glycosidic bond. Among the α -glucans, dextran, which is a polysaccharide, has been studied and used in many cases. The alpha-glucan is mainly connected by D-glucopyranose with a bond of alpha, 1 → 6, and branched points are connected by 1 → 2, 1 → 3 and 1 → 4. The beta-glucan active structure is a polysaccharide composed of glucose units, most of which are bound via beta-1, 3, which is a mode of glucose chain attachment. It can activate macrophage and neutrophilic leucocyte, so increasing the contents of leukocidin, cytokinin and special antibody and fully stimulating the immune system. The beta-glucan can quickly restore the capability of the injured body lymphocyte to generate the cell factor (IL-1) and effectively regulate the body immune function. A large number of experiments show that the beta-glucan can promote the in vivo IgM antibody to be generated so as to improve the humoral immunity capability. The glucan activated cell can stimulate a host non-specific defense mechanism, so that the glucan activated cell is widely noticed in the aspects of tumor, infectious diseases and wound treatment. Beta-1, 3 glucan extracted by a special step and free from endotoxin is recognized as a safe substance by the FDA in the United states and can be added to general foods, and many reports show that the oral administration of yeast beta-1, 3 glucan to mice can enhance the antibacterial phagocytosis of peritoneal cells.

In certain embodiments of the invention, the dextran powder is dissolved in water to form an external phase. In some specific embodiments, the external phase is formed using beta-glucan (e.g., soluble beta-glucan).

The dextran generally has a relatively high molecular weight, e.g., the dextran employed in the water-in-water composition of the present invention has a molecular weight in the range of 210⁵～5×10⁵g/mol。

In certain embodiments of the invention, the amount of natural high molecular weight polysaccharide polymer in the water-in-water composition is from 1% to about 20%, preferably from about 1% to about 10%, more preferably from about 2% to about 8%, more preferably from about 2% to about 6% by weight of the composition. In some embodiments, the amount of natural high molecular weight polysaccharide polymer in the water-in-water composition is from about 2% to about 5% by weight of the composition. In other embodiments, the amount of natural high molecular weight polysaccharide polymer in the water-in-water composition is from about 2% to about 3% by weight of the composition.

Active agent

The active agent is a commonly used functional raw material in cosmetics, has fat-soluble or alcohol-soluble characteristics, but is insoluble or slightly soluble in water, and can be applied to emulsified products when being added into the cosmetics and needing to be dissolved in a polyalcohol solvent in advance, but the application in water aqua products is greatly limited and still has the risk of precipitation. The water-in-water composition greatly reduces the precipitation risk of the active agent in aqueous products and improves the stability. The active agent of the present invention is preferably salicylic acid.

Salicylic acid

Salicylic acid can dissolve the substance (pigment) between horny layers to cause the horny layer to fall off, so that it can remove the horny layer accumulated too thick and promote metabolism. Salicylic acid can remove redundant horny layer and promote the rapid renewal of epidermal cells; if the epidermal cells are all fresh and full of vital tender cells, the skin can naturally recover smooth and delicate. In addition, the salicylic acid is fat-soluble, can permeate into the deep layer of pores along sebaceous glands secreting fat, is favorable for dissolving old accumulated cuticle in the pores, and improves the situation of pore blockage, so that the formation of acnes can be blocked, and the enlarged pores can be reduced. In the aspect of preventing acne, salicylic acid acts on cells of the hair follicle wall, can help to remove blocked hair follicles and correct abnormal cell shedding, can prevent the blockage of pores for slight acne and is most effective for blackheads. Salicylic acid functions to clean aged keratin, making the skin look fine and less prone to acne. Because salicylic acid has the excellent cosmetic properties, it is highly desirable to make it into a skin cosmetic product that exhibits its effects in lightening pigmented spots, reducing pores, removing acne, removing fine wrinkles, and improving sun exposure.

However, salicylic acid is difficult to be prepared into conventional aqueous cosmetics due to the fat solubility of the salicylic acid, and is difficult to be applied to conventional aqueous cosmetics.

The present invention is based on the following unexpected findings: polyethylene glycol is used as an inner phase and glucan is used as an outer phase, so that phase separation can be realized when certain concentration conditions are met, and finally the water-in-water composition capable of carrying the active agent is formed. In a particular embodiment of the invention, the active agent employed is salicylic acid. The water-in-water composition prepared by the invention realizes the loading of high-content salicylic acid in the water aqua product, namely, the water aqua composition meets the upper limit of 5 percent of medicinal skin external preparations and the upper limit of 2 percent of resident skin cosmetics, and keeps the stability for a long time. The invention prepares the composition capable of bearing high-content salicylic acid for the first time, and simultaneously can avoid the irritation of the salicylic acid.

In certain embodiments of the invention, it is preferred to control the ratio of the internal phase polyethylene glycol and salicylic acid in the water-in-water composition carrying salicylic acid. For example, the ratio of polyethylene glycol to salicylic acid may be controlled to be 9:1 or more to avoid crystallization of salicylic acid.

In certain embodiments of the invention, the salicylic acid may be present in the water-in-water composition in an amount up to about 5% by weight, preferably up to about 3% by weight, more preferably up to about 2% by weight. In some embodiments, the salicylic acid is present in the water-in-water composition in an amount from about 1% to about 5% by weight. In other embodiments, the salicylic acid is present in the water-in-water composition in an amount from about 2% to about 3% by weight.

Preparation method

The present inventors have found that a low irritation product comprising salicylic acid can be formed by first forming a water-in-water composition. The water-in-water composition may be formed using conventional techniques for forming compositions known in the cosmetic formulation art. For example, this may involve mixing a natural high molecular weight polysaccharide polymer with a cosmetically acceptable carrier to form an external phase, mixing salicylic acid with a polyol polymer to form an internal phase, and then adding the internal phase to the external phase under highly homogeneous process conditions to give the desired water-in-water composition. In certain embodiments of the present invention, the cosmetically acceptable carrier is an aqueous carrier (e.g., deionized water).

In certain embodiments of the invention, the inner and outer phases may each be heated to substantially the same temperature, e.g., greater than about 50 deg.C, e.g., about 80 deg.C. The inner phase can then be added to the outer phase and allowed to mix for a period of time sufficient to form a water-in-water composition. For example, the mixing time of the inner phase and the outer phase may be about 1 hour, 30 minutes, 20 minutes, or 10 minutes.

According to certain embodiments of the present invention, the addition of the inner phase to the outer phase is performed under homogenization process conditions. For example, the homogenization process conditions are a homogenization process at about 5000rpm to about 15000 rpm. In certain embodiments of the invention, the homogenization process conditions are a homogenization process of about 5000 to about 10000 rpm. In certain embodiments of the invention, the homogenization process conditions are a homogenization process at about 5000 to about 8000 rpm. Applying a homogenizing intensive blending step can further reduce the particle size of the composition. For example, the composition particle size is preferably from about 0.2 microns to about 10 microns, more preferably from about 0.5 microns to about 5 microns, more preferably from about 0.75 microns to about 5 microns, and most preferably from about 1 micron to about 5 microns.

After the inner phase is added to the outer phase, the composition can be cooled, for example, to less than 30 ℃ (e.g., to ambient conditions) to form a water-in-water composition comprising salicylic acid.

Further, during preparation of the internal phase, mixing may be continued at a speed of less than about 1000rpm (e.g., about 500rpm and 700rpm), for example, using a stirrer. Similarly, during preparation of the outer phase, mixing may be continued at a speed of less than about 1000rpm (e.g., about 500rpm and 700rpm), for example, using a stirrer.

Application method

The water-in-water compositions of the present invention are preferably stored in an environment of 0-25 c, where cold chain transportation is recommended.

The water-in-water compositions of the present invention may be topically applied to mammalian skin. In one embodiment, the skin is subject to acne problems. In another embodiment, the skin requires an exfoliating treatment. The water-in-water composition can be applied to skin in need of treatment according to a suitable treatment regimen, e.g., from up to 2 times per day to as little as 1 time per week (e.g., once per day, once every two days, once per week), and the like.

In certain embodiments, the water-in-water compositions of the present invention may also be used to treat other desired conditions associated with the skin. For example, the water-in-water compositions of the present invention can be used to treat post-inflammatory hyperpigmentation, to reduce pore size, to reduce sebum production, and to reduce scarring.

The technical aspects of the present invention will be described in detail below with reference to preferred embodiments, but the scope of the present invention is not limited to these embodiments, and the technical aspects of the present invention are intended to be described and not limited. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the manufacturer. All percentages and parts are by weight unless otherwise indicated.

The experimental materials used in the examples of the present invention are as follows:

example 1: preparation of water-in-water compositions

Scattering 8.16 parts by mass of glucan into 48.98 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 42.86 parts by mass of PEG400 to 70 ℃ to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 600rpm to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 2: preparation of water-in-water compositions

Scattering 6.12 parts by mass of glucan into 51.02 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 3: preparation of water-in-water compositions

Scattering 4.08 parts by mass of glucan into 53.06 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 4: preparation of water-in-water compositions

Scattering 2.84 parts by mass of glucan into 76.76 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 20.40 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 5: preparation of water-in-water compositions

Scattering 2.77 parts by mass of glucan into 74.78 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 22.45 parts by mass of PEG400 at room temperature to 80 ℃ to be used as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform transparent fluid, stirring, and cooling to room temperature to obtain water-in-water composition.

Example 6: preparation of water-in-water compositions

Scattering 2.65 parts by mass of glucan into 71.84 parts by mass of deionized water at room temperature, rapidly stirring at 550rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 25.51 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 7: preparation of water-in-water compositions

Scattering 2.62 parts by mass of glucan into 70.85 parts by mass of deionized water at room temperature, rapidly stirring at 550rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 26.53 parts by mass of PEG400 at room temperature to 80 ℃ to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 8: preparation of water-in-water compositions

Scattering 2.58 parts by mass of glucan into 69.87 parts by mass of deionized water at room temperature, rapidly stirring at 600rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 27.55 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 9: preparation of water-in-water compositions

Scattering 2.55 parts by mass of glucan into 68.88 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 28.57 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 10: preparation of water-in-water compositions

Scattering 2.2 parts by mass of glucan into 42.2 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 55.6 parts by mass of PEG400 to 80 ℃ to be used as an internal phase for later use; the inner phase was slowly added to the outer phase with rapid stirring at 700rpm to form an opaque flowing liquid, which was cooled to room temperature with continued stirring and a white precipitate was found at the bottom.

Example 11: preparation of water-in-water compositions

Scattering 2.1 parts by mass of glucan into 50.5 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 47.4 parts by mass of PEG400 to 80 ℃ to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 700rpm to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 12: preparation of water-in-water compositions

Scattering 2.1 parts by mass of glucan into 45.3 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 52.6 parts by mass of PEG400 to 80 ℃ to be used as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 700rpm to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 13: preparation of water-in-water compositions

Scattering 2.1 parts by mass of glucan into 40 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 57.9 parts by mass of PEG400 to 80 ℃ to serve as an internal phase for later use; the inner phase was slowly added to the outer phase with rapid stirring at 700rpm to form an opaque flowing liquid, which was cooled to room temperature with continued stirring and a white precipitate was found at the bottom.

Example 14: preparation of water-in-water compositions

Scattering 2.04 parts by mass of glucan into 77.55 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 20.41 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 15: preparation of water-in-water compositions

Scattering 2.04 parts by mass of glucan into 57.14 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 40.82 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 16: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 56 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 42 parts by mass of PEG400 to 70 ℃ to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 600rpm to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 17: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 56 parts by mass of deionized water at room temperature, rapidly stirring at 600rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

uniformly mixing 41 parts by mass of PEG400 and 1 part by mass of PEG14M at room temperature, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 650rpm to form uniform and uniform opaque viscous liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 18: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 56 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

uniformly mixing 40 parts by mass of PEG400 and 2 parts by mass of PEG14M at room temperature, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 700rpm to form uniform and uniform opaque viscous liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 19: preparation of water-in-water compositions

Scattering 1.9 parts by mass of glucan into 40.2 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 20: preparation of water-in-water compositions

Scattering 1.02 parts by mass of glucan into 56.12 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 21: preparation of water-in-water compositions

Scattering 0.51 mass part of glucan into 56.63 mass parts of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 42.86 parts by mass of PEG400 to 70 ℃ to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 600rpm to form uniform and consistent semitransparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 22: preparation of water-in-water compositions

uniformly mixing 45 parts by mass of PEG400 and 2.4 parts by mass of PEG14M at room temperature, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an inner phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 700rpm to form uniform and uniform opaque viscous liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 23: preparation of water-in-water compositions

uniformly mixing 45 parts by mass of PEG400 and 2.4 parts by mass of PEG14M at room temperature, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an inner phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, mixing, homogenizing for 10min to obtain uniform opaque viscous liquid, stirring, and cooling to room temperature to obtain water-in-water composition.

Example 24: preparation of water-in-water compositions

Scattering 2.47 parts by mass of glucan into 66.92 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

heating 30.61 parts by mass of PEG400 to 80 ℃ at room temperature to serve as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 25: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 66.92 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

uniformly mixing 29.08 parts by mass of PEG400 and 1.53 parts by mass of PEG14M at room temperature, rapidly stirring at 650rpm until the mixture is uniformly dispersed, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 7000rpm homogenization, homogenizing for 10min after mixing to form uniform opaque viscous liquid, and stirring and cooling to room temperature to obtain the water-in-water composition.

Example 26: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 54 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 42 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the condition of fast stirring at 700rpm to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 27: preparation of water-in-water compositions

adding 2 parts by mass of salicylic acid into 42 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 28: preparation of water-in-water compositions

Scattering 2.42 parts by mass of glucan into 65.58 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 30 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 29: preparation of water-in-water compositions

uniformly mixing 28.5 parts by mass of PEG400 and 1.5 parts by mass of PEG14M at room temperature, adding 2 parts by mass of salicylic acid into the mixed PEG400 and PEG14M solution at room temperature, rapidly stirring at 650rpm until the mixture is uniformly dispersed, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 7000rpm homogenization, homogenizing for 10min after mixing to form uniform opaque viscous liquid, and stirring and cooling to room temperature to obtain the water-in-water composition.

Example 30: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 45.3 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 5 parts by mass of salicylic acid into 47.7 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform opaque flowing liquid, stirring, and cooling to room temperature to obtain the water-in-water composition.

Example 31: preparation of water-in-water compositions

uniformly mixing 45.5 parts by mass of PEG400 and 2.2 parts by mass of PEG14M at room temperature, adding 5 parts by mass of salicylic acid into the mixed PEG400 and PEG14M solution at room temperature, rapidly stirring at 650rpm until the mixture is uniformly dispersed, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an inner phase for later use; slowly adding the inner phase into the outer phase under 7000rpm homogenization, homogenizing for 10min after mixing to form uniform opaque viscous liquid, and stirring and cooling to room temperature to obtain the water-in-water composition.

Example 32: preparation of water-in-water compositions

Scattering 8 parts by mass of glucan into 45 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 45 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 33: preparation of water-in-water compositions

Scattering 6 parts by mass of glucan into 49 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 43 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 34: preparation of water-in-water compositions

Scattering 4 parts by mass of glucan into 50 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 44 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 35: preparation of water-in-water compositions

Scattering 2.78 parts by mass of glucan into 75.22 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 20 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 36: preparation of water-in-water compositions

Scattering 2.71 parts by mass of glucan into 73.29 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 22 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform transparent fluid, stirring, and cooling to room temperature to obtain water-in-water composition.

Example 37: preparation of water-in-water compositions

Scattering 2.6 parts by mass of glucan into 70.4 parts by mass of deionized water at room temperature, rapidly stirring at 550rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 25 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 38: preparation of water-in-water compositions

Scattering 2.57 parts by mass of glucan into 69.43 parts by mass of deionized water at room temperature, rapidly stirring at 550rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 26 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 39: preparation of water-in-water compositions

Scattering 2.53 parts by mass of glucan into 68.47 parts by mass of deionized water at room temperature, rapidly stirring at 600rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 27 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 40: preparation of water-in-water compositions

Scattering 2.5 parts by mass of glucan into 67.5 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 28 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 41: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 51 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 5 parts by mass of salicylic acid into 42 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 7000rpm homogenization, homogenizing for 10min after mixing to form uniform opaque flowing liquid, and continuously stirring and cooling to room temperature to obtain the water-in-water composition.

Example 42: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 48 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 5 parts by mass of salicylic acid into 45 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform opaque flowing liquid, stirring, and cooling to room temperature to obtain the water-in-water composition.

Example 43: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 76 parts by mass of deionized water at room temperature, rapidly stirring at 500rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 44: preparation of water-in-water compositions

adding 2 parts by mass of salicylic acid into 40 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 45: preparation of water-in-water compositions

Scattering 1 part by mass of glucan into 55 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 42 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 46: preparation of water-in-water compositions

Scattering 0.5 part by mass of glucan into 55.5 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of salicylic acid into 42 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, mixing, homogenizing for 10min to obtain uniform translucent liquid, stirring, and cooling to room temperature to obtain the water-in-water composition.

Example 47: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 47 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 3 parts by mass of salicylic acid into 48 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 48: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 57.5 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling the glucan into a glucan water solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 0.5 part by mass of salicylic acid into 40 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 49: preparation of water-in-water compositions

Scattering 2 parts by mass of glucan into 52 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 1 part by mass of salicylic acid into 45 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 6000rpm homogenization, homogenizing for 10min after mixing to form uniform transparent flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 50: preparation of water-in-water compositions

adding 2 parts by mass of salicylic acid into 42 parts by mass of polypropylene glycol at room temperature, rapidly stirring at 650rpm until the salicylic acid is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under the homogenization state of 5000rpm, homogenizing for 10min after mixing to form uniform and uniform opaque flowing liquid, and continuously stirring and cooling to normal temperature to obtain the water-in-water composition.

Example 51: preparation of water-in-water compositions

uniformly mixing 45.5 parts by mass of polypropylene glycol and 2.2 parts by mass of polyethylene oxide at room temperature, adding 5 parts by mass of salicylic acid into the mixed polypropylene glycol and polyethylene oxide solution at room temperature, rapidly stirring at 650rpm until the mixture is uniformly dispersed, and heating to 80 ℃ to obtain transparent viscous uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase under 7000rpm homogenization, homogenizing for 10min after mixing to form uniform opaque viscous liquid, and stirring and cooling to room temperature to obtain the water-in-water composition.

Example 52: preparation of water-in-water compositions

Spreading 2 parts by mass of pullulan into 54 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the pullulan is uniformly dispersed, finally dispersing and swelling to form a pullulan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 53: preparation of water-in-water compositions

Spreading 2 parts by mass of pullulan into 45.3 parts by mass of deionized water at room temperature, rapidly stirring at 650rpm until the pullulan is uniformly dispersed, finally dispersing and swelling to form a pullulan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

Example 54: preparation of Water-in-Water composition (comparative example 1)

Scattering 2 parts by mass of glucan into 43 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 5 parts by mass of tetrahydrocurcumin into 50 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the tetrahydrocurcumin is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform transparent fluid, stirring, cooling to room temperature to obtain precipitate and obtain water-in-water composition.

Example 55: preparation of Water-in-Water composition (comparative example 2)

Scattering 2 parts by mass of glucan into 46 parts by mass of deionized water at room temperature, quickly stirring at 650rpm until the glucan is uniformly dispersed, finally dispersing and swelling to obtain a glucan aqueous solution, and heating to 80 ℃ to obtain an external phase for later use;

adding 2 parts by mass of tetrahydrocurcumin into 50 parts by mass of PEG400 at room temperature, rapidly stirring at 650rpm until the tetrahydrocurcumin is uniformly dispersed, and heating to 80 ℃ to obtain transparent uniform liquid serving as an internal phase for later use; slowly adding the inner phase into the outer phase at 6000rpm, mixing, homogenizing for 10min to obtain uniform transparent fluid, stirring, cooling to room temperature to obtain precipitate and obtain water-in-water composition.

Example 56 (exfoliating essence application example)

A water-in-water composition containing 2% salicylic acid was prepared according to the method of example 27 as an opaque flowing liquid with a viscosity of about 2000-4000 mPa.s as the textural appearance of the serum and used as an exfoliant for consumer trial experience testing.

Randomly selecting 5 females with the average age of 35 +/-2 years as a tester of the exfoliating essence, using the females after cleaning the skin at night, using the females once a week and continuously using the females for 2 weeks, and feeding back the effect of perceptively softening the cutin without one adverse reaction of the skin.

Example 57 (acne removing essence application example)

A water-in-water composition containing 2% salicylic acid was prepared according to the method of example 27 as an opaque flowing liquid with a viscosity of about 2000-4000 mPa-s as the textural appearance of the serum and used as a de-acne serum for consumer trial experience testing.

Randomly selecting 5 acne skin consumers as testers of the acne removing essence, wherein the average age is 25 +/-2 years, 3 female consumers and 2 male consumers. After the acne-removing cream is used for cleaning skin, the acne-removing cream is used once every two days, can be smeared on the face, can also be locally used for parts with serious acnes, is continuously used for 2 weeks, has obvious effects of reducing pores, removing acnes and diminishing inflammation, and does not have adverse reactions on the skin.

Example 58 (acne removing essence application example)

A water-in-water composition containing 2% salicylic acid was prepared according to the method of the example, and was an opaque liquid in appearance, with a viscosity of about 6000-10000 mPa-s, and was a textural appearance of a more viscous serum, and was used as a topical pox-spotting serum for consumer trial experience testing.

Selecting 5 consumers with skin problems of local pox or pox marks, carefully applying the skin problems to local parts with pox or pox marks by matching with cotton swabs and the like after cleaning the skin, and using the skin problems once a day. Waiting for the coated part to naturally absorb and dry (other things can be processed simultaneously in the waiting process), and carefully removing the coated part after a transparent invisible film is formed on the coated surface. After 2 weeks of continuous use, the acne cream has the appreciable effects of reducing acne and acne marks and has no adverse reaction to skin.

Example 59: temperature stability investigation

The temperature stability evaluation method is as follows: the samples prepared in examples 1-53 were placed in five incubator environments of 48 ℃, 40 ℃, ambient temperature (25 ℃), 4 ℃ and-18 ℃ for three months. And observing whether the sample is crystallized, layered, separated or settled. If the sample is not normally changed before and after a certain temperature condition for three months, the sample is represented as ok, if the upper and lower layering phenomena occur, the sample is represented as layering, if the crystallization phenomenon occurs, the sample is represented as crystallization, if the precipitation phenomenon occurs, the sample is represented as precipitation, if the precipitation phenomenon occurs, the sample is represented as deposition, and if the obvious color change phenomenon occurs, the sample is represented as color change. The results are shown in tables 1 to 2 below.

Table 1: temperature stability test (-18 ℃, 4 ℃, 25 ℃)

Note: w represents week and M represents month.

Table 2: temperature stability examination (40 ℃, 48 ℃)

Note: w represents week and M represents month.

From the temperature stability results of tables 1 and 2, the following points can be summarized:

first, examples 1-21 represent water-in-water compositions without salicylic acid, and examples 22-31 compare the effect of different processes (rapid agitation and high speed homogenization) on the preparation of water-in-water compositions with and without salicylic acid, respectively.

(1) As can be seen from examples 1 to 3, 15 and 20 to 21, the higher the glucan concentration, the higher the outer phase viscosity, and the better the stability of the resulting water-in-water composition, which is manifested by an improvement in stability at high temperatures (40 ℃ and 48 ℃); when the dextran concentration was reduced to around 0.5% (example 21), sedimentation occurred, i.e. the preparation of a water-in-water composition could not be achieved.

(2) Comparing examples 4-9 with examples 10-13, it is found that the concentration ratio of the inner phase and the outer phase needs to be controlled within a certain range, and when the concentration of the inner phase PEG is too low, the inner phase PEG and the outer phase dextran are mutually dissolved to form a transparent uniform liquid, and a water-in-water composition cannot be formed; when the concentration of the internal phase PEG is too high, above 55%, the preparation of the initial sample of the water-in-water composition according to the invention cannot be achieved.

(3) Examples 16 to 18 are the same internal and external phase ratio examples, the stability at RT (25 ℃) and low temperature (4 ℃ and-18 ℃) is better, and the viscosity of the internal phase increases with the increase of the molecular weight of PEG in the internal phase, so that the stability at high temperature (40 ℃ and 48 ℃) is improved; in example 11, compared with examples 16 to 18, the proportion of the inner phase PEG400 is further increased, and precipitation occurs only at room temperature for 1 month, which shows that the stability is reduced to a certain extent due to a higher proportion of the inner phase PEG; the conclusion of examples 16-18 is consistent with the conclusion that example 22 compared to example 11 and example 25 compared to example 24, the stability increased with increasing internal phase viscosity (internal phase PEG molecular weight).

(4) Example 23 the homogenization process resulted in smaller and more uniform emulsified particles than example 22 (compare photomicrograph comparison), and the effect on stability was not significant.

(5) Comparing examples 26 and 27, it was found that salicylic acid affected the formation of the interface between the inner and outer phase of the water-in-water composition, while the homogenization process helped to make the particles of the water-in-water composition system containing salicylic acid finer and more uniform than the stirring process, which is consistent with conclusion (4).

(6) Comparing examples 28 and 29, and 30 and 31, the effect of the concentration of PEG in the internal phase and the homogenization process on stability was found to be substantially consistent with the foregoing.

Examples 32-49 represent the preparation of water-in-water compositions containing salicylic acid.

(7) Examples 32-40 and examples 43-46 are water-in-water compositions containing 2% salicylic acid, and it was found by comparing examples 35-40 that when the concentration of PEG in the inner phase is too low, the inner phase becomes miscible with the outer phase dextran, forming a clear and homogeneous liquid, and a water-in-water composition cannot be formed, consistent with the previous conclusion (2), and that when the PEG concentration is too low, salicylic acid crystallizes out in the PEG phase.

(8) Examples 41 to 42 are water-in-water compositions containing 5% salicylic acid, the ratio of PEG to salicylic acid in the internal phase should preferably be not less than 9:1, otherwise salicylic acid will tend to crystallize out.

(9) Examples 32 to 34 and examples 43 to 46, the higher the dextran concentration, the higher the outer phase viscosity, and the better the stability of the resulting water-in-water composition, as expressed by the improved stability at high temperatures (40 ℃ and 48 ℃); when the dextran concentration was reduced to around 0.5% (example 46), sedimentation occurred, i.e. preparation of a water-in-water composition could not be achieved.

(10) Examples 47 to 49 are water-in-water compositions containing salicylic acid at different concentrations (0.5 to 3.0%), which demonstrate that water-in-water compositions containing salicylic acid at or below 5.0% can be prepared using the methods of the present invention.

(11) Examples 50-53 are water-in-water compositions with an inner phase of polypropylene glycol or polypropylene glycol and polyethylene oxide and an outer phase of dextran or pullulan, showing that the inner phase of the present invention can be of a molecular weight greater than 1X 10⁵One or more of polyethylene oxide, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, polyalcohol polymer and polymer (such as poloxamer) containing polyoxyethylene and polyoxypropylene segments with similar structure to the above substances; the external phase of the invention may be a moleculeThe amount is in the range of 2 × 10⁵To 5X 10⁵g/mol of one or more natural high molecular polysaccharide substances such as alpha-glucan, beta-glucan, agarose, chitin, pullulan, gelatinized starch, xanthan gum and the like.

(12) The stability problems of delamination, precipitation and the like can occur in the storage process of the currently obtained water-in-water composition samples under the high temperature conditions of 40 ℃ and 48 ℃ over time, and the stability of the preferred embodiments at the normal temperature of 25 ℃, 4 ℃ and-18 ℃ is relatively good, so that the water-in-water composition prepared by the invention needs to be stored in the environment of 0-25 ℃, and cold chain transportation is recommended if necessary.

Example 60: investigation of illumination stability

The method for evaluating the illumination stability comprises the following steps: the samples prepared in examples 1-53 were placed in a 25 ℃ thermostatted light incubator using a PERCINAL CU41L5 light box, USA, set at a constant temperature of 25 ℃ and set at a light parameter of 75UML by means of a dimmer, and examined for three months. And (5) observing whether the sample is layered or precipitated. If the sample is not normally changed before and after a certain temperature condition for three months, the sample is represented as ok, if the upper and lower layering phenomena occur, the sample is represented as layering, if the crystallization phenomenon occurs, the sample is represented as crystallization, if the precipitation phenomenon occurs, the sample is represented as precipitation, if the precipitation phenomenon occurs, the sample is represented as deposition, and if the obvious color change phenomenon occurs, the sample is represented as color change. The results are shown in Table 3.

Table 3: investigation of illumination stability

Note: w represents week and M represents month.

From the light stability results in table 3, the light has little influence on the water-in-water composition prepared by the present invention, the appearance has no obvious color change, and the rest stability conclusions are basically consistent with the stability situation at the normal temperature of 25 ℃.

Claims

1. A water-in-water composition carrying a high level of active agent comprising:

an external phase comprising a molecular weight in the range of 2 x 10⁵To 5X 10⁵g/mol of natural high molecular weight polysaccharide polymer, wherein the content of the natural high molecular weight polysaccharide polymer is 1-10 wt% based on the total weight of the composition.

2. The composition of claim 1, wherein the polyol polymer is selected from one or more of polyethylene glycol, polypropylene glycol, and polybutylene glycol.

3. The water-in-water composition of claim 2, wherein the polyol polymer is present in an amount of 40 to 45 wt.%, based on the total weight of the composition.

4. The composition according to claim 1, wherein the natural high molecular weight polysaccharide polymer is selected from the group consisting of: one or more of alpha-glucan, beta-glucan, agarose, chitin, pullulan, gelatinized starch and xanthan gum.

5. The water-in-water composition according to claim 4, wherein the natural high molecular weight polysaccharide polymer is contained in an amount of 2 to 6% by weight based on the total weight of the composition.

6. A composition according to claim 1, wherein the active agent is salicylic acid.

7. The water-in-water composition of claim 6, wherein the internal phase further comprises a molecular weight greater than 1 x 10⁵g/mol of polymer.

8. The water-in-water composition of claim 7, wherein the molecular weight is greater than 1 x 10⁵The g/mol polymer is selected from: one or more combinations of polyethylene oxide, polypropylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, gelatin, polyol polymers, and other polymers containing polyoxyethylene-polypropylene oxide blocks.

9. A method of making the water-in-water composition of claim 1, the method comprising the steps of:

10. The method of claim 9, wherein the homogenization conditions are 5000rpm to 15000 rpm.

11. The method of claim 10, wherein the water-in-water composition has an emulsion droplet size of 1 to 5 microns.

12. Use of the water-in-water composition according to any one of claims 1 to 8 in cosmetics.