Multiphase beads encapsulating recombinant collagen, preparation method thereof, and cosmetics

Abstract

The present application relates to the field of cosmetics, and to a multiphase bead that encapsulates recombinant collagen, a preparation method thereof, and cosmetics. The multiphase bead forms a multi-layer encapsulation structure; the multi-layer encapsulation structure includes: an outer layer, an intermediate layer, and an inner layer; the inner layer includes: a water-soluble active substance; the intermediate layer is an oil phase; the outer layer includes: a wall and a water phase, the water phase encapsulates the oil phase, the wall is encapsulated in the outermost layer, and the wall is calcium alginate. Multiphase bead with a water-in-oil-in-water structure is formed, and calcium alginate forms the outer shell of the multiphase bead. The oil phase is the intermediate phase, sandwiched between the water-soluble active substance and the outer wall; the water-soluble active substance is the innermost phase, encapsulated by the outer layer of calcium alginate and the intermediate oil layer; thereby realizing the preservation of water-soluble active substances such as recombinant collagen by encapsulation technology. It can effectively protect water-soluble active substances such as recombinant collagen, reduce the decomposition rate of water-soluble active substances such as recombinant collagen, and improve the activity of cosmetics.

Description

Technical Field

[0001] The present application relates to the field of cosmetics, and more specifically, to a multiphase gel bead encapsulating recombinant collagen, a preparation method thereof, and cosmetics. Background Art

[0002] Collagen has moisturizing and repairing properties, promoting cell metabolism, delaying aging, and maintaining skin's plumpness. It's a common moisturizing and anti-aging ingredient in the cosmetics industry. However, the protein's decomposition rate and activity are easily affected by external factors. Directly applying it to cosmetics can significantly reduce its effectiveness. Summary of the Invention

[0003] The purpose of the embodiments of the present application is to provide a multiphase gel bead encapsulating recombinant collagen, a preparation method thereof, and a cosmetic.

[0004] In a first aspect, the present application provides a multi-phase condensed bead, which forms a multi-layered wrapping structure; the multi-layered wrapping structure includes: an outer layer, an intermediate layer, and an inner layer;

[0005] The inner layer includes: a water-soluble active substance;

[0006] The middle layer is an oil phase;

[0007] The outer layer includes: a wall body and a water phase, the water phase wraps the oil phase, the wall body is wrapped in the outermost layer, and the wall body is calcium alginate.

[0008] In the above technical solution of the present application, a W / O / W structure (water-in-oil-in-water structure) is used to effectively encapsulate water-soluble active substances such as collagen, which can effectively improve the activity of water-soluble active substances such as collagen.

[0009] The multiphase beads mentioned in the present application form a W / O / W structure (water-in-oil-in-water structure) while calcium alginate forms the outer shell of the multiphase beads. The oil phase is the middle phase, sandwiched between the water-soluble active substance (for example, recombinant collagen solution) and the outer wall; the water-soluble active substance (for example, recombinant collagen solution) is the innermost phase, wrapped by the outer layer of calcium alginate and the middle oil layer; thus, the preservation of water-soluble active substances such as recombinant collagen is achieved by using wrapping technology. The application of such multiphase-wrapped beads in cosmetics can effectively protect water-soluble active substances such as recombinant collagen, reduce the decomposition rate of water-soluble active substances such as recombinant collagen, and improve the activity of cosmetics.

[0010] In other embodiments of the present application, the water-soluble active ingredient accounts for less than 1% of the oil phase in terms of mass percentage.

[0011] In the above technical solution, the mass of the water-soluble active substance accounts for less than 1% of the mass of the oil phase layer, and the encapsulation effect is excellent.

[0012] In other embodiments of the present application, the water-soluble active ingredient includes at least one of recombinant collagen, hydrolyzed elastin, acetyl hexapeptide-8, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, glycyrrhiza glabra root extract, arbutin, Rehmannia glutinosa root extract or Camellia japonica extract.

[0013] In other embodiments of the present application, the oil phase includes: an oil phase emollient and an oil phase thickener;

[0014] Optionally, the oil phase emollient includes at least one of caprylic / capric / succinic triglyceride, triethylhexanoin or squalane;

[0015] Optionally, the oil phase thickener includes castor oil / IPDI copolymer.

[0016] The above oil phase can well encapsulate water-soluble active ingredients.

[0017] In other embodiments of the present application, the oil phase further includes: an oil-soluble active ingredient.

[0018] In other embodiments of the present application, the outer layer further comprises an aqueous phase; the aqueous phase comprises an aqueous phase moisturizer, an aqueous phase thickener, and water;

[0019] Optionally, the aqueous phase moisturizer includes at least one of glycerin, dipropylene glycol, or PEG / PPG-14 / 7 dimethyl ether;

[0020] Optionally, the aqueous phase thickener includes at least one of xanthan gum, sodium alginate, gellan gum or agar.

[0021] In other embodiments of the present application, based on the total amount of the multi-phase condensed beads, the following are included in percentage by mass:

[0022] Water-soluble active ingredients 0.6% or less; wall 0.5% or less; the aqueous phase moisturizer 1.0-20.0%, the aqueous phase thickener 0.1-1.5%;

[0023] The oil phase emollient is less than 60%; the oil phase thickener is less than 5%;

[0024] The balance is the water.

[0025] In a second aspect, the present application provides a method for preparing the multiphase condensate beads provided in the first aspect, comprising:

[0026] Mixing an aqueous phase moisturizer, an aqueous phase thickener and water to obtain a homogeneous aqueous phase;

[0027] Mixing the oil phase emollient and the oil phase thickener to obtain a homogeneous oil phase;

[0028] uniformly mixing the water-soluble active ingredient with the oil phase to obtain a mixed solution;

[0029] The aqueous phase and the mixed solution are simultaneously dropped into the soaking solution containing calcium salt.

[0030] In other embodiments of the present application, the aqueous phase and the mixed solution are simultaneously dripped into the soaking solution containing the calcium salt, comprising:

[0031] The aqueous phase and the mixed solution are simultaneously dropped into the soaking solution containing calcium salt using a microfluidic device;

[0032] Optionally, the calcium salt includes calcium chloride or calcium lactate; optionally, the concentration of the soaking solution is 0.3% (w / w) to 2% (w / w).

[0033] In a third aspect, the present application provides a multi-phase gel bead encapsulating recombinant collagen, wherein the multi-phase gel bead forms a multi-layer encapsulation structure; the multi-layer encapsulation structure comprises: an outer layer, an intermediate layer, and an inner layer;

[0034] The inner layer is recombinant collagen; the middle layer is the oil phase; the outer layer includes: a wall and a water phase, the water phase wraps the oil phase, and the wall is wrapped in the outermost layer, and the wall is calcium alginate.

[0035] Calculated by mass percentage, the recombinant collagen accounts for less than 1% of the oil phase content.

[0036] Further optionally, in some embodiments of the present application, the recombinant collagen accounts for 0.25%-1% of the oil phase content by mass. Further optionally, in some embodiments of the present application, the recombinant collagen accounts for 0.5%-1% of the oil phase content by mass.

[0037] In a fourth aspect, the present application provides a cosmetic comprising the multi-phase beads provided in any of the aforementioned aspects. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without creative work.

[0039] Figure 1 This is a microscopic image of the multiphase beads encapsulating recombinant collagen in Example 1 observed under an optical microscope;

[0040] Figure 2 This is a microscopic image of the multiphase beads encapsulating recombinant collagen of Example 3 observed under an optical microscope;

[0041] Figure 3 The microstructure of the dual-phase beads of Comparative Example 1 observed under an optical microscope;

[0042] Figure 4 A microfluidic device is provided in some embodiments of the present application. DETAILED DESCRIPTION

[0043] In order to make the purpose, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments.

[0044] Therefore, the following detailed description of the embodiments of the present application is not intended to limit the scope of the present application for protection, but merely represents selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0045] In the cosmetics industry, microbeads on the market are usually used to encapsulate oil-soluble active ingredients, while encapsulating water-soluble active ingredients is more difficult.

[0046] The encapsulation of proteins is more difficult than that of some water-soluble active substances. The difficulties are: (1) mild reaction conditions are required and proteins are sensitive to external factors such as temperature, pH, ionic strength, and organic solvents, which can easily affect their activity and functionality; (2) proteins are biological macromolecules, and their encapsulation efficiency and stability are easily restricted to varying degrees.

[0047] Currently, liposome encapsulation is a common method for protein encapsulation, but it still has several obvious problems: (1) Liposomes are mostly phospholipid membranes, and the adsorption of polar groups of protein molecules to the polar regions of the phospholipid membrane will affect the encapsulation efficiency and stability. (2) The use of organic solvents, high-speed shearing, pH, heating temperature and other factors in the preparation process of this method can easily affect the activity, encapsulation efficiency and stability of the protein.

[0048] The embodiment of the present application provides a multi-phase condensed bead, which forms a multi-layer wrapped structure; the multi-layer wrapped structure includes: an outer layer, an intermediate layer and an inner layer;

[0049] The inner layer includes: a water-soluble active substance;

[0050] The middle layer is an oil phase;

[0051] The outer layer includes: a wall body and a water phase, the water phase wraps the oil phase, the wall body is wrapped in the outermost layer, and the wall body is calcium alginate.

[0052] In the above technical solution, a multiphase bead with a W / O / W structure (oil-in-water-in-water structure) is formed, and calcium alginate forms the outer shell of the multiphase bead. The oil phase is the middle phase, sandwiched between the water-soluble active substance (e.g., recombinant collagen solution) and the outer wall; the water-soluble active substance (e.g., recombinant collagen solution) is the innermost phase, encapsulated by the outer layer of calcium alginate and the middle oil layer. This achieves the preservation of water-soluble active substances such as recombinant collagen using encapsulation technology. The application of such multiphase encapsulated beads in cosmetics can effectively protect water-soluble active substances such as recombinant collagen, reduce the decomposition rate of water-soluble active substances such as recombinant collagen, and enhance the activity of the cosmetics.

[0053] The present application creatively adopts a W / O / W structure (water-in-oil-in-water structure) to achieve the encapsulation of water-soluble active substances such as proteins. Compared with the liposome encapsulation method in the prior art, it does not require organic solvents and will not produce changes in factors such as high-speed shear, pH, and heating temperature that affect protein activity. Compared with liposome encapsulation, it has a better effect.

[0054] Furthermore, in some embodiments of the present application, the water-soluble active ingredient accounts for less than 1% of the oil phase in terms of mass percentage.

[0055] Further optionally, illustratively, in some embodiments of the present application, the water-soluble active ingredient accounts for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9% or 1% of the oil phase by mass.

[0056] Alternatively, in some embodiments of the present invention, the water-soluble active ingredient accounts for 0.25%-1% of the oil phase content by mass. Alternatively, in some embodiments of the present invention, the water-soluble active ingredient accounts for 0.5%-1% of the oil phase content by mass.

[0057] Furthermore, in some embodiments of the present application, the water-soluble active ingredient includes at least one of: recombinant collagen, hydrolyzed elastin, acetyl hexapeptide-8, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, glycyrrhiza glabra root extract, arbutin, Rehmannia glutinosa root extract or Camellia japonica extract.

[0058] Illustratively, in some embodiments of the present application, the water-soluble active ingredient is selected from: any one of recombinant collagen, hydrolyzed elastin, acetyl hexapeptide-8, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, glycyrrhiza glabra root extract, arbutin, Rehmannia glutinosa root extract or Camellia japonica extract.

[0059] Alternatively, in some embodiments of the present application, the water-soluble active ingredient is selected from: a mixture of recombinant collagen and hydrolyzed elastin; the two can be mixed in any proportion; or in some embodiments of the present application, the water-soluble active ingredient is selected from: a mixture of recombinant collagen and acetyl hexapeptide-8 and palmitoyl tripeptide-8, and the three can be mixed in any proportion; or in some embodiments of the present application, the water-soluble active ingredient is selected from: a mixture of recombinant collagen, palmitoyl pentapeptide-4, glycyrrhiza glabra root extract, arbutin, Rehmannia glutinosa root extract and Camellia japonica extract, and the six can be mixed in any proportion.

[0060] Furthermore, in some embodiments of the present application, the oil phase includes: an oil phase emollient and an oil phase thickener.

[0061] Furthermore, in some embodiments of the present application, the oil-phase emollient includes at least one of caprylic / capric / succinic triglyceride, triethylhexanoin, or squalane.

[0062] For example, in some embodiments of the present application, the oil phase emollient is selected from any one of caprylic / capric / succinic acid triglyceride, triethylhexanoin, or squalane. Alternatively, in some embodiments of the present application, the oil phase emollient is selected from a mixture of caprylic / capric / succinic acid triglyceride, triethylhexanoin, and squalane, and the three can be mixed in any proportion.

[0063] Furthermore, in some embodiments of the present application, the oil phase thickener includes: castor oil / IPDI copolymer.

[0064] Furthermore, in some embodiments of the present application, the oil phase further includes: an oil-soluble active ingredient.

[0065] Further optionally, in some embodiments of the present application, the above-mentioned oil-soluble active ingredients include:

[0066] At least one of ubiquinone, tocopherol or lithospermum officinale extract.

[0067] For example, in some embodiments of the present application, the above-mentioned oil-soluble active ingredient is selected from: any one of ubiquinone, tocopherol or lithospermum officinale extract; or the above-mentioned oil-soluble active ingredient is selected from: a mixture of ubiquinone, tocopherol and lithospermum officinale extract, and the three can be mixed in any proportion.

[0068] Furthermore, in some embodiments of the present application, the outer layer also includes an aqueous phase; the aqueous phase includes an aqueous phase moisturizer, an aqueous phase thickener and water.

[0069] Furthermore, in some embodiments of the present application, the aqueous phase moisturizer includes at least one of glycerin, dipropylene glycol, or PEG / PPG-14 / 7 dimethyl ether.

[0070] Illustratively, in some embodiments of the present application, the above-mentioned aqueous phase moisturizer is selected from: any one of glycerin, dipropylene glycol or PEG / PPG-14 / 7 dimethyl ether; or the above-mentioned aqueous phase moisturizer is selected from: a mixture of glycerin, dipropylene glycol, and PEG / PPG-14 / 7 dimethyl ether, and the three can be mixed in any proportion.

[0071] Furthermore, in some embodiments of the present application, the aqueous phase thickener includes at least one of xanthan gum, sodium alginate, gellan gum or agar.

[0072] For example, in some embodiments of the present application, the aqueous phase thickener is selected from: any one of xanthan gum, sodium alginate, gellan gum or agar; or the aqueous phase thickener is selected from: a mixture of xanthan gum, sodium alginate, gellan gum and agar, and the four can be mixed in any proportion.

[0073] Furthermore, in some embodiments of the present application, based on the total amount of the multiphase condensed beads, the following are included in percentage by mass:

[0074] Water-soluble active ingredients 0.6% or less; wall 0.5% or less; the aqueous phase moisturizer 1.0-20.0%, the aqueous phase thickener 0.1-1.5%;

[0075] The oil phase emollient is less than 60%; the oil phase thickener is less than 5%;

[0076] The balance is the water.

[0077] Further optionally, in some embodiments of the present application, based on the total amount of the multiphase condensed beads, the following are included in percentage by mass:

[0078] Water-soluble active ingredients 0.15-0.6% or less; wall 0.1-0.5%; the aqueous phase moisturizer 1.0-20.0%, the aqueous phase thickener 0.1-1.5%;

[0079] The oil phase emollient is 56.1 to 60% or less; the oil phase thickener is 2.4 to 5% or less;

[0080] The balance is the water.

[0081] For example, in some embodiments of the present application, based on the total of the water phase and the oil phase, the following are included in percentage by mass:

[0082] Water-soluble active ingredients 0.15%, 0.16%, 0.18%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6% or ranges between any two of the foregoing;

[0083] Aqueous phase moisturizer 1.0%, 2.0%, 5.0%, 6.0%, 8.0%, 10.0%, 12.0%, 15.0%, 18.0%, 20.0% or any range between two of the foregoing;

[0084] Aqueous phase thickener 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5% or any range between two of the foregoing;

[0085] Oil phase emollient 60%, 55%, 50%, 45%, 40%, 35%, 30%, 20%, 10% or any range between the foregoing;

[0086] Oil phase thickener 5%, 4%, 3%, 2%, 1% or any range between the foregoing;

[0087] 0.1%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5% of the wall or any range between two of the foregoing;

[0088] The balance is water.

[0089] The present application provides a method for preparing multiphase condensate beads, comprising:

[0090] Mixing an aqueous phase moisturizer, an aqueous phase thickener and water to obtain a homogeneous aqueous phase;

[0091] Mixing the oil phase emollient and the oil phase thickener to obtain a homogeneous oil phase;

[0092] uniformly mixing the water-soluble active ingredient with the oil phase to obtain a mixed solution;

[0093] The aqueous phase and the mixed solution are simultaneously dropped into the soaking solution containing calcium salt.

[0094] The aqueous phase and the mixed liquid are simultaneously dripped into the soaking liquid containing calcium salt to form a multiphase condensed bead with a W / O / W structure (water-in-oil-in-water structure), and sodium alginate reacts with calcium ions to form the shell of the multiphase condensed bead. For example, sodium alginate and calcium chloride react to form calcium alginate, which becomes the outermost wall. The oil phase is the middle phase, sandwiched between the water-soluble active substance (for example, recombinant collagen solution) and the outer wall; the water-soluble active substance (for example, recombinant collagen solution) is the innermost phase, wrapped by the outer layer of calcium alginate and the middle oil layer; thereby realizing the preservation of water-soluble active substances such as recombinant collagen using wrapping technology. The application of such multiphase-wrapped condensed beads in cosmetics can effectively protect water-soluble active substances such as collagen, reduce the decomposition rate of water-soluble active substances such as collagen, and improve the activity of cosmetics.

[0095] The present application creatively adopts a W / O / W structure (water-in-oil-in-water structure) to achieve the encapsulation of water-soluble active substances, solving the technical problem of the difficulty in encapsulating water-soluble active substances in the prior art.

[0096] Furthermore, in some embodiments of the present application, the method for preparing the multiphase condensate beads comprises the following steps:

[0097] Step S1: Preparation: Mix an aqueous phase moisturizer, an aqueous phase thickener, and water to obtain a homogeneous aqueous phase.

[0098] Furthermore, in some embodiments of the present application, the preparation of mixing the aqueous phase moisturizer, the aqueous phase thickener and water to obtain a homogeneous aqueous phase comprises:

[0099] Mix the aqueous phase moisturizer, aqueous phase thickener and water and heat to above 90°C, keep warm for 10min to 30min, 3000rpm to 6000rpm, and homogenize for 1min to 3min.

[0100] Illustratively, in some embodiments of the present application, deionized water, glycerin, dipropylene glycol, xanthan gum, gellan gum, sodium alginate, phenoxyethanol, PEG / PPG-14 / 7 dimethyl ether, and agar are mixed in the aforementioned ratio and heated to above 90° C., kept warm for 10 to 30 minutes, at 3000 to 6000 rpm, and homogenized for 1 to 3 minutes.

[0101] Illustratively, in some embodiments of the present application, the heating temperature is 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C or a range between any two of the foregoing; the insulation time is 10min, 12min, 15min, 16min, 18min, 20min, 22min, 25min, 28min, 30min or a range between any two of the foregoing; 3000rpm, 3500rpm, 4000rpm, 4500rpm, 5000rpm, 5500rpm, 6000rpm or a range between any two of the foregoing; and the homogenization is 1min, 2min, 3min.

[0102] Step S2: mixing the oil phase emollient and the oil phase thickener to obtain a homogeneous oil phase.

[0103] Furthermore, in some embodiments of the present application, the above-mentioned oil phase emollient and oil phase thickener are mixed, heated to 90° C. to 100° C., and dissolved and stirred evenly.

[0104] Further optionally, in some embodiments of the present application, the aforementioned oil-phase emollient and oil-phase thickener are mixed, heated to 90°C to 100°C, and stirred to dissolve and uniformly dissolve. After cooling to below 80°C, the oil-soluble active ingredient is added. For example, ubiquinone is added to dissolve and disperse uniformly when the temperature drops to 70°C to 80°C, and tocopherol and lithospermum extract are added after cooling to below 40°C to 50°C.

[0105] Illustratively, in some embodiments of the present application, the above-mentioned oil phase emollient and oil phase thickener are mixed, heated to 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C or a temperature range between any two of the foregoing, and dissolved and stirred evenly; then when the temperature is reduced to 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C or a temperature range between any two of the foregoing, ubiquinone is added to dissolve and disperse evenly; and when the temperature is cooled to 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, 50°C or a temperature range between any two of the foregoing, tocopherol and lithospermum extract are added.

[0106] Further, illustratively, in some embodiments of the present application, caprylic / capric / succinic triglyceride, glyceryl tri(ethylhexanoate), squalane, and castor oil / IPDI copolymer are mixed in the aforementioned proportions, heated to 95°C and dissolved and stirred evenly, and when the temperature drops to 75°C, ubiquinone is added to dissolve and disperse evenly, and after cooling to below 45°C, tocopherol and lithospermum extract are added.

[0107] Step S3, preparing a soaking solution: preparing calcium chloride or calcium lactate into a soaking solution with a concentration of 0.3% (w / w) to 2% (w / w).

[0108] Illustratively, in some embodiments of the present application, calcium chloride or calcium lactate is configured into a soaking solution of 0.3% (w / w), 0.4% (w / w), 0.5% (w / w), 0.8% (w / w), 0.9% (w / w), 1% (w / w), 1.2% (w / w), 1.5% (w / w) or 2% (w / w).

[0109] Step S4: uniformly mix the water-soluble active ingredient with the oil phase obtained in the above step S2 to obtain a mixed solution.

[0110] Furthermore, in some embodiments of the present application, the water-soluble active ingredients include at least one of recombinant collagen, hydrolyzed elastin, acetyl hexapeptide-8, palmitoyl tripeptide-8, palmitoyl pentapeptide-4, glycyrrhiza glabra root extract, arbutin, Rehmannia root extract or Camellia extract.

[0111] For example, by weight percentage, the recombinant collagen accounting for less than 1% of the oil phase content is mixed evenly with the oil phase prepared in step S2 to obtain a mixed solution. Further alternatively, for example, the recombinant collagen accounting for 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9% or 1% of the oil phase content is mixed evenly with the oil phase prepared in step S2 to obtain a mixed solution.

[0112] Further optionally, in some embodiments of the present application, the water-soluble active ingredient is added to the oil phase prepared in the aforementioned step S2 and stirred at a rotation speed of 100 rpm to 200 rpm for 10 min to 20 min.

[0113] For example, in some embodiments of the present application, the stirring speed is 100 rpm, 110 rpm, 120 rpm, 130 rpm, 140 rpm, 150 rpm, 160 rpm, 170 rpm, 180 rpm, 190 rpm or 200 rpm. The stirring time is 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min or 20 min.

[0114] Step S5: The aqueous phase obtained in the above step S1 and the mixed solution obtained in the above step S4 are simultaneously dripped into the soaking solution containing calcium salt obtained in the above step S3.

[0115] In the above technical solution, the aqueous phase and the mixed liquid are simultaneously dripped into the soaking liquid containing calcium salt to form a multiphase condensed bead with a W / O / W structure (water-in-oil-in-water structure), and at the same time, sodium alginate reacts with calcium ions to form the shell of the multiphase condensed bead. For example, sodium alginate and calcium chloride react to form calcium alginate, which becomes the outermost wall. The oil phase is the middle phase, sandwiched between the water-soluble active substance (for example, recombinant collagen solution) and the outer wall; the water-soluble active substance (for example, recombinant collagen solution) is the innermost phase, which is wrapped by the outer layer of calcium alginate and the middle oil layer; thereby realizing the preservation of water-soluble active substances such as recombinant collagen by wrapping technology. The application of such multiphase wrapped condensed beads in cosmetics can effectively protect water-soluble active substances such as collagen, reduce the decomposition rate of water-soluble active substances such as collagen, and improve the activity of cosmetics.

[0116] Furthermore, in some embodiments of the present application, the aqueous phase and the mixed solution are simultaneously dripped into the soaking solution containing the calcium salt, comprising:

[0117] The aqueous phase and the mixed solution are simultaneously dropped into the soaking solution containing calcium salt using a microfluidic device.

[0118] Further optionally, in some embodiments of the present application, the above-mentioned microfluidic device includes: a microfluidic T-tube.

[0119] Further optionally, in some embodiments of the present application, the aqueous phase and the mixed solution are simultaneously dripped into the soaking solution containing the calcium salt through the above-mentioned microfluidic T-tube by means of pump force.

[0120] For example, referring to Figure 4 In some embodiments of the present application, the above-mentioned microfluidic device includes:

[0121] Pumping device 1, pumping device 2 and microfluidic T-tube; pumping device 1 and pumping device 2 are respectively connected to the microfluidic T-tube; liquid is introduced from pumping device 1 and pumping device 2 respectively, merged into the microfluidic T-tube, and dripped out from the dripping outlet of the microfluidic T-tube. A reaction pool is provided at the dripping outlet of the microfluidic T-tube, and an immersion liquid containing a calcium salt is accommodated in the reaction pool, so that the aqueous phase and the mixed liquid can be dripped into the immersion liquid containing the calcium salt simultaneously through the above-mentioned microfluidic T-tube.

[0122] Further optionally, illustratively, the mixed liquid is introduced from pumping device 1 and the aqueous phase is introduced from pumping device 2; or the aqueous phase is introduced from pumping device 1 and the mixed liquid is introduced from pumping device 2.

[0123] Step S6. Further, in some embodiments of the present application, the reactant obtained in the aforementioned step S5 is filtered to obtain multiphase beads.

[0124] Further optionally, the multiphase condensation beads are cleaned, illustratively using deionized water, to remove the soaking liquid on the surface of the multiphase condensation beads.

[0125] The above-mentioned method of the present application can, on the one hand, effectively expand the possibility of using water-based active substances such as recombinant collagen in the cosmetics industry in related new dosage forms; secondly, there are more water-soluble active substances in the cosmetics industry. However, due to technical limitations, most of the beads on the market are oil-core wrapped beads, and there are fewer packages of water-soluble active substances. The technology involved in this application can wrap water-soluble active substances (such as collagen) that are sensitive to external factors and easily affected by activity; break through technical barriers; thirdly, the solution of this application, because it is a multi-phase beads, can not only wrap water-soluble active substances, but also double-wrap water-soluble and oil-soluble active substances, greatly improving the efficacy of the beads.

[0126] Some embodiments of the present application provide a multiphase gel bead encapsulating recombinant collagen, wherein the multiphase gel bead forms a multilayer encapsulation structure; the multilayer encapsulation structure comprises: an outer layer, a middle layer, and an inner layer;

[0127] The inner layer is recombinant collagen; the middle layer is the oil phase; the outer layer includes: a wall and a water phase, the water phase wraps the oil phase, and the wall is wrapped in the outermost layer, and the wall is calcium alginate.

[0128] Calculated by mass percentage, the recombinant collagen accounts for less than 1% of the oil phase content.

[0129] The recombinant collagen mentioned above in this application can be purchased commercially.

[0130] Some embodiments of the present application provide a cosmetic comprising the multi-phase beads provided by any of the aforementioned embodiments.

[0131] The features and performance of the present invention are further described in detail below with reference to the embodiments:

[0132] Preparation method of multiphase beads

[0133] A multiphase gel bead is provided, which is prepared according to the following steps:

[0134] Step (1), preparing aqueous phase A: recombinant collagen solution;

[0135] Step (2), preparing aqueous phase B: deionized water, glycerol, dipropylene glycol, xanthan gum, gellan gum, sodium alginate, phenoxyethanol, PEG / PPG-14 / 7 dimethyl ether, and agar were mixed according to the proportions in Table 1 and heated to above 90° C., kept warm for 20 min, and homogenized at 8000 rpm for 2 min;

[0136] Step (3), preparing the oil phase: caprylic / capric / succinic triglyceride, triethylhexanoin, squalane, and castor oil / IPDI copolymer are mixed according to the proportions in Table 1, heated to 95°C to dissolve and stir evenly, and when the temperature drops to 75°C, ubiquinone is added to dissolve and disperse evenly, and after cooling to below 45°C, tocopherol and lithospermum extract are added;

[0137] Step (4), preparing a soaking solution: preparing calcium chloride or calcium lactate into a 0.3% (w / w) soaking solution;

[0138] Step (5), add the aqueous phase A into the prepared oil phase (3) according to the component contents in Table 1 and stir evenly at 150 rpm for 15 min to obtain a mixture;

[0139] Step (6), use the instructions attached Figure 4 The microfluidic T-tube device shown uses a pump to simultaneously pump the aqueous phase B produced in step (2) and the mixed material produced in step (5) into the calcium chloride solution produced in step (4), forming multiphase beads with a W / O / W structure (water-in-oil-in-water structure). Sodium alginate and calcium chloride react to form calcium alginate, which forms the outermost wall; the oil phase is the middle phase, sandwiched between the water-soluble active ingredient and the outer wall; and the recombinant collagen solution is the innermost phase, surrounded by the outer calcium alginate layer and the middle oil layer.

[0140] The multiphase condensed beads of each embodiment were prepared according to the above-mentioned multiphase condensed beads preparation method. The specific raw material components and their contents of each embodiment are shown in Table 1. Unit: (g).

[0141] Comparative Example 1

[0142] Provided are gel beads, which are prepared using the aforementioned multi-phase gel bead preparation method, except that: step (1) is omitted; adaptively, in step (5), only the "oil phase" prepared in step (3) is stirred; adaptively, in step (6), the "mixture" is replaced by the uniformly stirred "oil phase" prepared in step (5).

[0143] Comparative Example 2-Comparative Example 3

[0144] Provided is a gel bead, which is prepared using the aforementioned multi-phase gel bead preparation method, except that:

[0145] Step (6) is replaced by:

[0146] The aqueous phase B prepared in step (2) and the mixture prepared in step (5) were mixed and stirred at 150 rpm for 15 min.

[0147] The specific raw material components and their contents of each comparative example are shown in Table 1. Unit: (g).

[0148] Table 1

[0149]

[0150]

[0151]

Performance test

[0152] The performance of the beads of various embodiments or comparative examples was tested.

[0153] 1. Stability test method

[0154] The condensed bead samples of each embodiment and comparative example were treated at high temperature, low temperature and room temperature, and the state of the condensed beads was observed.

[0155] The treatment parameters are as follows: high temperature (45°C, 6 months), low temperature (-18°C, 6 months), and normal temperature (25°C, 6 months).

[0156] The test results are shown in Table 2.

[0157] Table 2

[0158]

[0159] It can be seen from the test results in the above table that the samples of the condensed beads provided in each embodiment have not changed in spherical shape and molding effect after being treated at high temperature (45°C, 6 months), low temperature (-18°C, 6 months) and room temperature (25°C, 6 months), showing excellent stability.

[0160] Comparative Examples 2 and 3 failed to form microbeads of good spherical size initially, and the size of the formed microbeads was uneven. Comparative Examples 2 and 3 failed to successfully produce heterogeneous beads encapsulating recombinant collagen with good feasibility and stability.

[0161] Moreover, after being treated at high temperature (45°C, 6 months), low temperature (-18°C, 6 months), and room temperature (25°C, 6 months), Comparative Examples 2 and 3 exhibited problems such as oil floating and coagulation at room temperature and high temperature; their stability was poor.

[0162] 2. Electron microscope structure observation

[0163] The microstructures of Example 1, Example 3, and Comparative Example 1 were observed using an optical microscope.

[0164] Test results as per instructions Figure 1 and Figure 2 、 Figure 3 shown.

[0165] Figure 1 、 Figure 2 These are the multiphase beads encapsulating recombinant collagen observed in Example 1 and Example 3, Figure 3 This is the oil-core dual-phase condensed bead of Comparative Example 1.

[0166] like Figure 1 As shown, in Example 1, there is a spherical water-soluble active substance recombinant collagen in the center, and an oil phase is between the recombinant collagen and the outer wall, which proves that the method of the present application can achieve the encapsulation of recombinant collagen and the oil-soluble active substance at the same time.

[0167] Furthermore, compared with Example 1 ( Figure 1 ) and Example 3 ( Figure 2 ) microscopic observation diagram, it can be found that as the amount of encapsulated collagen increases, the spherical water-soluble active substances inside become denser, and the mass of the water-soluble active substances accounts for less than 1% of the mass of the oil phase layer, indicating an excellent encapsulation effect.

[0168] Furthermore, if Figure 3 As shown, the comparative example 1 contains only the biphasic gel beads with an oil core, and no spherical water-soluble substance in the center, and the comparative example 1 fails to encapsulate the recombinant collagen.

[0169] 3. Application of multiphase beads in cosmetics

[0170] The multiphase beads prepared in this application were filtered, washed, and dried, and then placed into the following three commonly used formulations for testing, including an aqueous essence matrix, a microemulsion essence matrix, and an essence oil matrix.

[0171] Table 3 Matrix raw material components and their contents (w / w%)

[0172]

[0173]

[0174] Specific preparation method of matrix:

[0175] (1) Preparation method of aqueous essence matrix:

[0176] a. Dilute the aminomethyl propanol in phase A 10-fold and set aside;

[0177] b. Heat the other raw materials in phase A to 80°C, keep warm for 20 minutes, and then homogenize at 8000 rpm for 1 minute; stir to cool, add pre-made aminomethyl propanol, stir and cool to 38°C, then discharge and cool to room temperature.

[0178] (2) Preparation method of microemulsion essence matrix:

[0179] a. Mix 1% glycerol and 5% butylene glycol in phase A with phase B, heat to 65°C, keep warm for 15 minutes, and set aside;

[0180] b. Dilute the aminomethyl propanol in phase A 10-fold and set aside;

[0181] c. Heat the other raw materials in phase A to 80°C, keep warm for 20 minutes, and homogenize at 8000 rpm for 1 minute; stir and cool, then add the pre-prepared aminomethyl propanol;

[0182] d. Add the mixed glycerol, butylene glycol and phase B to the homogenized phase A;

[0183] e. Continue stirring and cool to 38°C, then discharge and cool to room temperature.

[0184] (3) Preparation method of essential oil matrix:

[0185] Stir and heat phase B until mixed and then cool to room temperature.

[0186] [Application of multiphase beads encapsulating recombinant collagen in the matrix of various serum formulations]

[0187] The multiphase beads encapsulating the recombinant collagen in Example 3 of the present application were dispersed in an aqueous essence matrix, a microemulsion essence matrix or an essence oil matrix to prepare cosmetics, and then the performance of the three cosmetics was tested respectively.

[0188] The test results are shown in Table 4.

[0189] Table 4 (w / w%)

[0190]

[0191] As can be seen from the results in the above table, when the multiphase beads encapsulating recombinant collagen in Example 3 of the present application are placed in the aqueous essence matrix and the microemulsion essence matrix, the dispersion state is good, and both the dropper and pump head packaging materials can obtain a good skin feel.

[0192] On the other hand, the multiphase beads encapsulating recombinant collagen in Example 3 also exhibited good dispersion when dispersed in an essential oil matrix with a certain consistency. However, compared to pure aqueous essences and microemulsion essences, the multiphase beads in the essential oil matrix exhibited a noticeable graininess when applied through the dropper packaging, resulting in poor absorption. However, this phenomenon can be resolved by replacing the packaging material. Essential oils using pump-type packaging exhibited faster absorption.

[0193] In summary, the recombinant collagen multiphase beads of this application can be used in a variety of cosmetic matrices, and the above data can be used as a partial reference. Furthermore, the packaging material, matrix consistency, and wall thickness of the multiphase beads may have a certain impact on skin feel and dispersion stability, and therefore can be adjusted appropriately based on actual conditions.

[0194] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A multiphase condensate bead, characterized in that: The multi-phase condensed beads form a multi-layered wrapping structure; The multi-layer packaging structure includes: an outer layer, a middle layer and an inner layer; The inner layer includes: a water-soluble active substance; The middle layer is an oil phase; The outer layer comprises: a wall body and a water phase, wherein the water phase wraps the oil phase, and the wall body is wrapped in the outermost layer, and the wall body is calcium alginate; The water-soluble active ingredient is recombinant collagen; In terms of mass percentage, the water-soluble active ingredient accounts for less than 1% of the oil phase content; The aqueous phase raw materials include deionized water, glycerin, dipropylene glycol, xanthan gum, gellan gum, sodium alginate, phenoxyethanol, PEG / PPG-14 / 7 dimethyl ether, and agar; the aqueous phase moisturizer includes glycerin, dipropylene glycol, PEG / PPG-14 / 7 dimethyl ether; the aqueous phase thickener includes xanthan gum, sodium alginate, gellan gum, and agar; The oil phase raw materials are composed of: caprylic / capric / succinic acid triglyceride, tri(ethylhexanoin), squalane, castor oil / IPDI copolymer, ubiquinone, tocopherol, and lithospermum officinale extract; the oil phase emollients include: caprylic / capric / succinic acid triglyceride, tri(ethylhexanoin), and squalane; the oil phase thickener includes: castor oil / IPDI copolymer; The preparation of the multiphase condensate beads comprises: Step (1), prepare aqueous phase A: recombinant collagen solution; Step (2), preparing aqueous phase B: mixing and heating the aqueous phase raw materials to above 90°C, keeping warm for 20 min, and homogenizing at 8000 rpm for 2 min; Step (3), preparing the oil phase: caprylic / capric / succinic acid triglyceride, triethylhexanoin, squalane, and castor oil / IPDI copolymer are mixed, heated to 95°C and stirred to dissolve evenly, and when the temperature drops to 75°C, ubiquinone is added to dissolve and disperse evenly, and after cooling to below 45°C, tocopherol and lithospermum extract are added; Step (4), preparing a soaking solution: preparing calcium chloride or calcium lactate into a 0.3% (w / w) soaking solution; Step (5), add the aqueous phase A into the prepared oil phase and stir evenly at 150 rpm for 15 min to obtain a mixture; Step (6): using a microfluidic T-tube device, the aqueous phase B prepared in step (2) and the mixed material body prepared in step (5) are simultaneously drained into the calcium chloride solution prepared in step (4) by means of a pump.

2. The multiphase condensate beads according to claim 1, characterized in that Based on the total amount of the multiphase condensed beads, the following are included in percentage by mass: Water-soluble active ingredients 0.6% or less; wall 0.5% or less; the aqueous phase moisturizer 1.0-20.0%, the aqueous phase thickener 0.1-1.5%; the soaking liquid 0.1%-0.5%; The oil phase emollient is less than 60%; the oil phase thickener is less than 5%; The balance is the water.

3. The method for preparing the multiphase condensate beads according to any one of claims 1 to 2, characterized in that: include: Step (1), prepare aqueous phase A: recombinant collagen solution; Step (2), preparing aqueous phase B: mixing and heating the aqueous phase raw materials to above 90°C, keeping warm for 20 min, and homogenizing at 8000 rpm for 2 min; Step (3), preparing the oil phase: caprylic / capric / succinic acid triglyceride, triethylhexanoin, squalane, and castor oil / IPDI copolymer are mixed, heated to 95°C and stirred to dissolve evenly, and when the temperature drops to 75°C, ubiquinone is added to dissolve and disperse evenly, and after cooling to below 45°C, tocopherol and lithospermum extract are added; Step (4), preparing a soaking solution: preparing calcium chloride or calcium lactate into a 0.3% (w / w) soaking solution; Step (5), add the aqueous phase A into the prepared oil phase and stir evenly at 150 rpm for 15 min to obtain a mixture; Step (6): using a microfluidic T-tube device, the aqueous phase B prepared in step (2) and the mixed material body prepared in step (5) are simultaneously drained into the calcium chloride solution prepared in step (4) by means of a pump.

4. The method for preparing multiphase condensed beads according to claim 3, characterized in that: Based on the total amount of the multiphase condensed beads, the following are included in percentage by mass: The water-soluble active ingredient is less than 0.6%; the water-phase moisturizer is 1.0% to 20.0%, the water-phase thickener is 0.1% to 1.5%; the oil-phase emollient is less than 60%; the oil-phase thickener is less than 5%; the soaking liquid is 0.1% to 0.5%; and the balance is water.

5. A cosmetic, characterized in that: The cosmetic comprises the multi-phase beads according to any one of claims 1 to 2.

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