A collagen supermolecule, and a preparation method and application thereof

Abstract

The present application relates to the technical field of supramolecular, in particular to a collagen supramolecule, a preparation method and application thereof, the collagen supramolecule is prepared by taking collagen, a stabilizer, an alcohol solvent, glycerol, an ionic liquid and water as raw materials, the preparation method of the collagen supramolecule is simple and easy to operate, and the prepared collagen supramolecule has high stability. Meanwhile, in the collagen supramolecule, the collagen can not only be used as one of active ingredients to improve the skin condition, but also be used as a carrier of active ingredients to improve the solubility and transdermal performance of various active ingredients including the collagen itself, so as to solve the defects in the prior art.

Description

Technical Field

[0001] This invention relates to the field of supramolecular technology, and in particular to a collagen supramolecular body, its preparation method, and its application. Background Technology

[0002] Collagen is a type of protein composed of amino acids. It is crucial for human growth and metabolism, serving as a major component connecting organs and muscles, and a vital part of the intercellular matrix. The main functions of collagen are maintaining the physiological functions and shape of tissues and organs, and repairing damaged tissues. Skin is the largest organ in the human body, and collagen makes up about 70% of it, primarily located in the dermis, forming the fibrous tissue structure beneath the epidermis and the dermal matrix. Collagen can bind large amounts of water, making it essential for maintaining skin tension and resilience, and is the material basis for maintaining plump and full skin. With age and the influence of external factors, human skin gradually ages. When collagen in the dermis is oxidized and broken down, the skin becomes dry, loose, and wrinkles appear. The skin loses its supporting function for the epidermis, resulting in wrinkles.

[0003] Collagen, as a biomaterial, possesses excellent biocompatibility, low immunogenicity, and the ability to promote cell growth and wound repair. Therefore, it is frequently added as an active ingredient in topical skincare products. However, it is well known that collagen has a large molecular weight, making it difficult to directly reach the dermis to improve skin condition. Simultaneously, due to its unique structure and function, collagen also holds significant potential as a carrier for active ingredients. Currently, collagen carriers are mostly prepared in the form of collagen membranes, collagen sponges, and microspheres. These carriers, such as collagen microspheres, often use chemical cross-linking agents to solidify the collagen during preparation. However, cross-linking agents such as glutaraldehyde and formaldehyde have very significant toxic side effects on the human body. Therefore, the safety of collagen as an oral product and its irritation potential as a topical product still need to be verified and addressed. Summary of the Invention

[0004] To address the aforementioned technical problems, the present invention aims to provide a collagen supramolecular body, its preparation method, and its applications. The preparation method of the collagen supramolecular body is simple and easy to implement, and the prepared collagen supramolecular body exhibits high stability. Furthermore, in this collagen supramolecular body, collagen can not only serve as one of the active ingredients to improve skin condition, but also as a carrier for loading active ingredients, thereby enhancing the solubility and transdermal properties of various active ingredients, including collagen itself, to overcome the deficiencies existing in the prior art.

[0005] To achieve the above-mentioned technical effects, the present invention adopts the following technical solution:

[0006] A collagen supramolecular body is prepared from the following raw materials in parts by weight: 0.5-10 parts collagen, 0.1-10 parts stabilizer, 5-25 parts alcohol solvent, 2-10 parts glycerol, 0.1-4 parts ionic liquid, and 7-1000 parts water.

[0007] Preferably, the collagen supramolecular body further includes active ingredients, and the active ingredients are any one or more of skin care active ingredients or pharmaceutical active ingredients.

[0008] More preferably, the skincare active ingredient is selected from any one or more of the following: ascorbyl glucoside, glyceryl glucoside, ascorbic acid, tetrahydrocurcumin, salicylic acid, tocopherol, ferulic acid, resveratrol, panthenol, glutathione, ceramide, arbutin, astaxanthin, niacinamide, 4-butylresorcinol, phloretin, hydroxypropyltetrahydropyranotriol, ergothioneine, ectoine, polyquaternium-51, hydroxypinazone retinate, palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, palmitoyl hexapeptide-12, palmitoyl tripeptide-8, nonapeptide-1, and palmitoyl pentapeptide-4.

[0009] More preferably, the pharmaceutical active ingredient can be an oral active ingredient or a topical active ingredient, and even more preferably a topical active ingredient, and the topical active ingredient is preferably selected from any one or more of retinoic acid, isotretinoin, tazarotene, adapalene, bezarotine, mupirocin, fusidic acid, compound polymyxin B, erythromycin, ofloxacin, clindamycin metronidazole, and benzoyl peroxide.

[0010] More preferably, the amount of the active ingredient added is 0.01 to 100% of the collagen protein content, preferably 0.1 to 30%.

[0011] Preferably, the collagen supramolecular body is prepared from the following raw materials in parts by weight: 0.5-10 parts collagen, 0.1-10 parts stabilizer, 5-25 parts alcohol solvent, 2-10 parts glycerol, 0.1-4 parts ionic liquid, and 7-100 parts water.

[0012] Preferably, the collagen is any one of collagen, collagen extract, hydrolyzed collagen, soluble collagen, deer bone collagen, protoplasmic collagen, and recombinant type III human collagen.

[0013] Preferably, the stabilizer is a cationic stabilizer, and is preferably selected from: myristyltrimethylammonium bromide, stearyltrimethylammonium bromide, lauryltrimethylammonium bromide, dicocarbamate dimethylammonium chloride, PEG-15 cococarbamate methylammonium chloride, PEG-2 cococarbamate methylammonium chloride, PEG-5 stearylammonium chloride, PG-hydroxyethylcellulose cococarbamate dimethylammonium chloride, PG-hydroxyethylcellulose stearyldimethylammonium chloride, PPG-25 diethylmethylammonium chloride, ricinoleic acid ammonium propyltrimethylammonium chloride, locust bean gum hydroxypropyltrimethylammonium chloride, locust bean hydroxypropyltrimethylammonium chloride, soybean oil-based trimethylammonium chloride, soybean oil ammonium propylbenzyldimethylammonium chloride, starch hydroxypropyltrimethylammonium chloride, etc. ammonium chloride, diC12-15 alkyl dimethyl ammonium chloride, dialcyl dimethyl ammonium chloride, diceryl dimethyl ammonium chloride, ditallow dimethyl ammonium chloride, dihydroxypropyl PEG-5 linoleyl ammonium chloride, octadecyl trimethyl ammonium chloride, distearate dimethyl ammonium chloride, distearate ethyl dimethyl ammonium chloride, dipalmitoyl ethyl dimethyl ammonium chloride, panthenol hydroxypropyl stearyl dimethyl ammonium chloride, guar gum hydroxypropyl trimethyl ammonium chloride, cetearyl dimethyl ammonium chloride, cetearyl trimethyl ammonium chloride, polymethacrylamide propyl trimethyl ammonium chloride, cassia gum hydroxypropyl trimethyl ammonium chloride, tallow trimethyl ammonium chloride, dextran hydroxypropyl trimethyl ammonium chloride, hydroxypropyl guar gum hydroxypropyl trimethyl ammonium chloride Methylammonium chloride, hydroxypropyl bis-hydroxyethyl dimethylammonium chloride, hydroxypropyl distearate dimethylammonium chloride, hydroxypropyl oxidized starch PG-trimethylammonium chloride, hydroxycetylhydroxyethyl dimethylammonium chloride, hydroxyethyl betainepropyl dimethylammonium chloride, hydroxyethyl oleyl dimethylammonium chloride, ginseng hydroxypropyl trimethylammonium chloride, cinnamamidopropyl trimethylammonium chloride, lactamidopropyl trimethylammonium chloride, tricerylmethylammonium chloride, behenylbenzyl dimethylammonium chloride, behenyl trimethylammonium chloride, behenamidopropyl PG-dimethylammonium chloride, behenyloxy PG-trimethylammonium chloride, dodecanebenzyl trimethylammonium chloride, dodecanehexadecyl trimethylammonium chloride, bishydroxyethyl bis-hydroxypropyl stearylammonium chloride, Octyl dodecyl trimethylammonium chloride, cocoyl trimethylammonium chloride, cocamidopropyl PG-dimethylammonium chloride, stearyl trimethylammonium chloride, stearamide propyl dimethyl benzyl ammonium chloride, stearoxypropyl trimethylammonium chloride, oleyl benzyl dimethylammonium chloride, oleamide propyl PG-dimethylammonium chloride, lauryl methyl glucetol polyether-10-hydroxypropyl dimethylammonium chloride, lauryl trimethylammonium chloride, lauroyl PG-trimethylammonium chloride, palmitamide propyl trimethylammonium chloride, or any one or more of the following: trimethyl-2,3-diolenooxypropylammonium chloride (DOTMA), trimethyl-2,3-dioleoyloxypropylammonium bromide (DOTAP), dimethyl trifluoroacetate-2...3-Dioleoyloxypropyl-2-(2-Sperminecarbamoylamino)ethylammonium (DOSPA), Trimethyldodecylammonium bromide (DTAB), Trimethyltetradecylammonium bromide (TTAB), Trimethylhexadecylammonium bromide (CTAB), Dimethylbisoctadecylammonium bromide (DDAB), Dimethyl-2-hydroxyethyl-2,3-dioleoyloxypropylammonium bromide (DORI), Dimethyl-2-hydroxyethyl-2,3-dioleoyloxypropylammonium bromide (DORIE), Dimethyl-3-hydroxypropyl-2,3-dioleoyloxypropylammonium bromide (DORIE-HP), Dimethyl-4-hydroxybutyl-2,3-dioleoyloxypropylammonium bromide The following are possible combinations of one or more of the following: dioleoyl-5-hydroxypentyl-2,3-dioleenooxypropylammonium bromide (DORIE-HPc), dimethyl-2-hydroxyethyl-2,3-dihexadecopropylammonium bromide (DPRIE), dimethyl-2-hydroxyethyl-2,3-dioctadecyloxypropylammonium bromide (DSRIE), dimethyl-2-hydroxyethyl-2,3-ditetradecyloxypropylammonium bromide (DMRIE), N-(2-argininoyl)-N',N'-dioctadecylglycineamide (DOGS), and 1,2-dioleoyl-3-succinyl-sn-glycerolcholine ester (DOSC).

[0014] More preferably, the stabilizer is selected from any one or more of myristyltrimethylammonium bromide, stearyltrimethylammonium bromide, lauryltrimethylammonium bromide, discoyldimethylammonium chloride, and distearyldimethylammonium chloride, or any combination of any one or more of trimethylhexadecylammonium bromide (CTAB), dimethyl dioctadecylammonium bromide (DDAB), trimethyl-2,3-diolenopropylammonium chloride (DOTMA), and trimethyl-2,3-dioleoylpropylammonium bromide (DOTAP).

[0015] It should be noted that, when implementing this invention, the type of stabilizer used can be selected according to the intended use of the collagen supramolecular body to ensure compliance with relevant regulatory requirements.

[0016] Preferably, the alcohol solvent is selected from any one or more of ethanol, propylene glycol, butanediol, pentanediol, or hexanediol.

[0017] More preferably, the alcohol solvent is selected from any one or more of ethanol, 1,2-butanediol, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, or 1,6-hexanediol.

[0018] Preferably, the ionic liquid is matrine-coconut oil ionic liquid.

[0019] Secondly, the present invention also provides a method for preparing collagen supramolecular bodies, comprising the following steps:

[0020] S1: Prepare an aqueous phase and an oil phase separately. The oil phase includes alcohol solvents, stabilizers, and ionic liquids, while the aqueous phase includes collagen, glycerol, and water.

[0021] S2: Mix the above aqueous phase and oil phase, and prepare the primary emulsion by high-speed shearing;

[0022] S3: The above colostrum is homogenized under high pressure to prepare a collagen supramolecular solution, wherein the collagen supramolecular solution contains collagen supramolecular bodies.

[0023] Preferably, in the above method for preparing collagen supramolecular bodies, if it is necessary to add active ingredients, the active ingredients can be selectively added to the aqueous phase and / or oil phase in S1.

[0024] Preferably, the preparation temperature of both the aqueous phase and the oil phase is 40–50°C.

[0025] Preferably, the high-speed shearing time in S1 is 1 to 5 minutes, more preferably 1 to 4 minutes; the high-speed shearing speed is 5000 to 12000 rpm.

[0026] Preferably, the high-pressure homogenization conditions in S2 are: homogenization pressure of 300-800 bar and homogenization cycle number of 3-8 times.

[0027] Thirdly, the present invention also provides a collagen supramolecular body provided in the first aspect above, or a collagen supramolecular body prepared by the preparation method of collagen supramolecular body provided in the second aspect, for any aspect of the preparation of food, health products, cosmetics, skin care products, feed or medicines for human or animal use, preferably for any aspect of the preparation of skin care products, cosmetics or topical medicines.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] Firstly, this invention prepares collagen into nanoscale supramolecular bodies, enabling it to serve as a carrier for active ingredients. This improves the absorption and penetration of other active ingredients, while the collagen itself can also function as an active ingredient. This is particularly advantageous for applications in topical pharmaceuticals and skincare products, where this collagen supramolecular body offers significant technological advantages over existing technologies. Specifically, when used in the preparation of topical products, the collagen supramolecular body acts as a carrier to carry at least one or more active ingredients. These active ingredients, along with the collagen, penetrate the epidermis and reach the dermis to exert their effects. Furthermore, the collagen supramolecular body provided by this invention not only promotes collagen penetration into the skin, fulfilling its supporting function and plumping the skin, but also synergistically carries multiple active ingredients, providing anti-wrinkle, antioxidant, and whitening effects—a dual benefit.

[0030] Furthermore, if the aforementioned collagen supramolecular bodies are used orally, they can effectively improve the solubility of active ingredients. Therefore, these collagen supramolecular bodies also have great application value in improving the bioavailability of active ingredients.

[0031] Furthermore, since the collagen supramolecular bodies provided by this invention can effectively enhance the transdermal absorption of various active ingredients, the dosage of these ingredients can be significantly reduced in practical applications, thus minimizing allergic reactions and improving safety. Simultaneously, due to their excellent biocompatibility and high stability, collagen supramolecular bodies can be applied in multiple fields, particularly in cosmetics and skincare, where they can play a significant role in effectively improving the transdermal absorption of various beauty-enhancing active ingredients, demonstrating immense development value.

[0032] Finally, the collagen supramolecular bodies prepared by the method of the present invention have good stability and uniform particle size. The preparation method is simple, feasible, easy to control, and can be mass-produced with high production efficiency. Attached Figure Description

[0033] Figure 1 This is a photograph of the appearance of the blank collagen supramolecular solution prepared in Example 1 of the present invention;

[0034] Figure 2 This is a transmission electron microscope image of the blank collagen supramolecular solution prepared in Example 1 of the present invention;

[0035] Figure 3 The particle size test results are for a blank collagen supramolecular solution prepared in Example 1 of this invention.

[0036] Figure 4 The particle size test results are for a collagen supramolecular product solution loaded with tetrahydrocurcumin prepared in Example 2 of this invention.

[0037] Figure 5 The particle size test results are for a collagen supramolecular product solution loaded with salicylic acid prepared in Example 3 of the present invention.

[0038] Figure 6 The particle size test results are for a collagen supramolecular product solution loaded with ascorbate glucoside prepared in Example 4 of this invention.

[0039] Figure 7 The particle size test results are for a collagen supramolecular product solution loaded with palmitoyl tripeptide-1 prepared in Example 5 of this invention.

[0040] Figure 8 The particle size test results are for a collagen solution prepared in Comparative Example 2 of this invention.

[0041] Figure 9 The particle size test results are for the mixture solution I prepared in Comparative Example 3 of this invention.

[0042] Figure 10 The particle size test results are for the supramolecular solution I prepared in Comparative Example 4 of this invention.

[0043] Figure 11 The appearance stability test results of Examples 1 to 5 provided in Example 6 of the present invention;

[0044] Figure 12 The encapsulation efficiency stability test results of Example 4 provided in Example 6 of the present invention;

[0045] Figure 13 The encapsulation efficiency stability test results of Comparative Example 4 provided in Embodiment 6 of the present invention;

[0046] Figure 14 The particle size stability test results of Example 4 provided in Example 6 of the present invention;

[0047] Figure 15 The particle size stability test results of Comparative Example 4 provided in Example 6 of this invention;

[0048] Figure 16 The results show the comparison of skin retention amount between Example 4 and Comparative Examples 1, 2, and 4 provided in Example 6 of the present invention. Detailed Implementation

[0049] The embodiments of the technical solution of the present invention will be described in detail below with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and are therefore merely examples and should not be used to limit the scope of protection of the present invention. Unless otherwise specified, the test methods used in the following embodiments are conventional methods; materials, reagents, or instruments whose manufacturers are not specified are commercially available reagents and materials, and conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer.

[0050] It should be noted that the matrine coconut oil ionic liquid in the following examples was purchased from Shenzhen Xuanjia Biotechnology Co., Ltd. The matrine coconut oil ionic liquid is an ionic compound that is liquid at room temperature, prepared by using matrine, an extract of the Chinese herbal medicine Sophora flavescens, as a cationic precursor and bio-based coconut oil fatty acid as an anionic precursor.

[0051] Example 1

[0052] This embodiment is the first preparation embodiment of the present invention. This embodiment provides a preparation of a collagen supramolecular solution. The collagen supramolecular solution contains blank collagen supramolecular bodies. The blank collagen supramolecular bodies are not loaded with active ingredients. Such blank collagen supramolecular bodies can be directly used as skin care products, thereby using collagen as the sole active ingredient to improve skin condition. At the same time, such blank collagen supramolecular bodies can also be used as carriers for loading active ingredients.

[0053] The collagen supramolecular solution provided in this embodiment is prepared according to the following steps:

[0054] S1: Prepare the aqueous phase and oil phase separately, specifically as follows:

[0055] The oil phase consists of 5 parts ethanol, 0.1 parts myristyltrimethylammonium bromide, and 0.1 parts matrine coconut oil ionic liquid. The above-mentioned raw materials are heated to a set temperature of 40°C and stirred to dissolve and mix thoroughly to obtain the oil phase.

[0056] The aqueous phase consists of 0.5 parts collagen, 2 parts glycerin, and water (to bring the aqueous phase system to 100 parts). Weigh the above-mentioned parts by weight of the raw materials, mix them, heat to the set temperature of 40°C, and stir to dissolve and mix thoroughly to obtain the aqueous phase.

[0057] S2: The oil phase obtained above is added to the aqueous phase and sheared at high speed for 1 min at a speed of 5000 rpm to obtain collagen supramolecular colostrum;

[0058] S3: The colostrum obtained above is subjected to high-pressure homogenization at 300 bar and cycled 3 times to obtain a blank collagen supramolecular solution containing blank collagen supramolecular bodies.

[0059] Example 2

[0060] This embodiment is the second preparation embodiment of the present invention. This embodiment provides a preparation of a collagen supramolecular solution loaded with tetrahydrocurcumin. The collagen supramolecular solution loaded with tetrahydrocurcumin can be added as a raw material for skin care products or cosmetics.

[0061] Tetrahydrocurcumin, derived from the hydrogenation of curcumin isolated from the rhizome of the ginger plant (Curcuma longa), is a natural functional skin-whitening ingredient.

[0062] The collagen supramolecular product solution loaded with tetrahydrocurcumin provided in this embodiment is prepared according to the following steps:

[0063] S1: Prepare the aqueous phase and oil phase separately, specifically as follows:

[0064] The oil phase includes 25 parts of 1,4-butanediol, 10 parts of tetrahydrocurcumin, 2 parts of stearyltrimethylammonium bromide, and 0.1 parts of matrine coconut oil ionic liquid. The above-mentioned raw materials are heated to a set temperature of 60°C and stirred to dissolve and mix thoroughly to obtain the oil phase.

[0065] The aqueous phase consists of 8 parts hydrolyzed collagen, 8 parts glycerin, and water (to bring the aqueous phase system to 100 parts). Weigh the above-mentioned parts by weight of the raw materials, mix them, heat to the set temperature of 60°C, and stir to dissolve and mix thoroughly to obtain the aqueous phase.

[0066] S2: The oil phase obtained above is added to the aqueous phase and sheared at high speed for 4 minutes at a speed of 6000 rpm to obtain collagen supramolecular colostrum;

[0067] S3: The colostrum obtained above was homogenized under high pressure at 300 bar and cycled 8 times to obtain a collagen supramolecular solution loaded with tetrahydrocurcumin.

[0068] Example 3

[0069] This embodiment is the third preparation embodiment of the present invention. This embodiment provides a preparation of a collagen supramolecular solution loaded with salicylic acid. The collagen supramolecular solution loaded with salicylic acid can be added as a raw material for skin care products or cosmetics.

[0070] Salicylic acid is a β-hydroxy acid, a fat-soluble organic acid that can penetrate deep into the pores along the sebaceous glands, dissolving the buildup that clogs the pores. It has the effect of dissolving blackheads and shrinking pores, and is often added as an ingredient in functional skin care products.

[0071] The collagen supramolecular solution loaded with salicylic acid provided in this embodiment is prepared according to the following steps:

[0072] S1: Prepare the aqueous phase and oil phase separately, specifically as follows:

[0073] The oil phase includes 15 parts of 1,2-pentanediol, 3 parts of salicylic acid, 0.5 parts of lauryltrimethylammonium bromide, and 4 parts of matrine coconut oil ionic liquid. The above-mentioned raw materials are heated to a set temperature of 60°C and stirred to dissolve and mix thoroughly to obtain the oil phase.

[0074] The aqueous phase consists of 6 parts collagen extract, 6 parts glycerin, and water (to bring the aqueous phase system to 100 parts). Weigh the above-mentioned parts by weight of the raw materials, mix them, heat to the set temperature of 60°C, and stir to dissolve and mix thoroughly to obtain the aqueous phase.

[0075] S2: The oil phase obtained above is added to the aqueous phase and sheared at high speed for 2 minutes at a speed of 8000 rpm to obtain collagen supramolecular colostrum;

[0076] S3: The colostrum obtained above is subjected to high-pressure homogenization at 500 bar and cycled 6 times to obtain a collagen supramolecular product solution loaded with salicylic acid.

[0077] Example 4

[0078] This embodiment is the fourth preparation embodiment of the present invention. This embodiment provides a preparation of a collagen supramolecular solution loaded with ascorbate glucoside. This collagen supramolecular solution loaded with ascorbate glucoside can be added as a raw material for skin care products or cosmetics.

[0079] Ascorbyl Glucoside (AA2G), also known as vitamin C glycoside, is a derivative of vitamin C. It mainly inhibits the activity of tyrosinase and also inhibits the production of melanin. It is often used as a whitening active ingredient added to skin care products.

[0080] The collagen supramolecular solution loaded with ascorbate glucoside provided in this embodiment is prepared according to the following steps:

[0081] S1: Prepare the aqueous phase and oil phase separately, specifically as follows:

[0082] The oil phase includes 15 parts of 1,3-propanediol, 1 part of dicocoyldimethylammonium chloride, and 3 parts of matrine coconut oil ionic liquid. The above-mentioned raw materials are heated to a set temperature of 60°C and stirred to dissolve and mix thoroughly to obtain the oil phase.

[0083] The aqueous phase includes 10 parts soluble collagen, 5 parts ascorbate glucoside, 10 parts glycerol, and water (to bring the aqueous phase system to 100 parts). Weigh the above-mentioned parts by weight of raw materials, mix them, heat to the set temperature of 60°C, and stir to dissolve and mix thoroughly to obtain the aqueous phase.

[0084] S2: The oil phase obtained above is added to the aqueous phase and sheared at high speed for 2 minutes at a speed of 12000 rpm to obtain collagen supramolecular colostrum;

[0085] S3: The colostrum obtained above was homogenized under high pressure at 800 bar and cycled 5 times to obtain a collagen supramolecular solution loaded with ascorbate glucoside.

[0086] Example 5

[0087] This embodiment is the fifth preparation embodiment of the present invention. The embodiment provides a preparation of a collagen supramolecular solution loaded with palmitoyl tripeptide-1. This collagen supramolecular solution loaded with palmitoyl tripeptide-1 can be added as a raw material for skin care products or cosmetics.

[0088] Palmitoyl tripeptide-1 is a commonly used cosmetic raw material. Related experimental studies have shown that 5 ppm of palmitoyl tripeptide-1 and 0.05% vitamin A have comparable activity in promoting the synthesis of collagen and glycosaminoglycans, and have good anti-wrinkle and anti-aging effects, so it can be used as a raw material for skin care products.

[0089] The collagen supramolecular solution loaded with palmitoyl tripeptide-1 provided in this embodiment is prepared according to the following steps:

[0090] S1: Prepare the aqueous phase and oil phase separately, specifically as follows:

[0091] The oil phase includes 13 parts of 1,3-butanediol, 0.5 parts of palmitoyl tripeptide-1, 0.5 parts of distearate dimethyl ammonium chloride, and 1 part of matrine coconut oil ionic liquid. The above-mentioned raw materials are heated to a set temperature of 50°C and stirred to dissolve and mix thoroughly to obtain the oil phase.

[0092] The aqueous phase consists of 7 parts soluble collagen, 8 parts glycerin, and water (to bring the aqueous phase system to 100 parts). Weigh the above-mentioned parts by weight of the raw materials, mix them, heat to the set temperature of 50°C, and stir to dissolve and mix thoroughly to obtain the aqueous phase.

[0093] S2: The oil phase obtained above is added to the aqueous phase and sheared at high speed for 1 min at a speed of 12000 rpm to obtain collagen supramolecular colostrum;

[0094] S3: The colostrum obtained above was homogenized under high pressure at 600 bar and cycled 5 times to obtain a collagen supramolecular solution loaded with palmitoyl tripeptide-1.

[0095] Comparative Example 1

[0096] This embodiment is the first comparative example of the present invention. This comparative example provides an ascorbate glucoside solution prepared in a conventional manner, and the specific preparation method is as follows:

[0097] Weigh out ascorbate glucoside and water, and uniformly disperse ascorbate glucoside in water at 60℃ to prepare a 5% ascorbate glucoside solution.

[0098] Comparative Example 2

[0099] This embodiment is the second comparative example of the present invention. This comparative example provides a method for preparing a collagen solution without active ingredients, and the specific preparation method is as follows:

[0100] Weigh out soluble collagen and disperse it evenly in water at 60°C to prepare a collagen solution with a concentration of 10%.

[0101] Comparative Example 3

[0102] This embodiment is the third comparative example of the present invention. This comparative example provides an ascorbate glucoside collagen mixture solution I that was not prepared using the method of the present invention. The ascorbate glucoside collagen mixture solution I is prepared by the following method:

[0103] Weigh 15 parts of 1,3-propanediol and 1 part of dicosyldimethylammonium chloride, mix them and heat to a set temperature of 60°C, stir to dissolve and mix thoroughly to obtain the oil phase.

[0104] Weigh out 10 parts of soluble collagen, 5 parts of ascorbate glucoside, 10 parts of glycerol, 3 parts of matrine coconut oil ionic liquid, and water (to make up to 100 parts of the aqueous phase system). Mix them at the set temperature of 60°C and stir until fully dissolved to obtain the aqueous phase.

[0105] Add the oil phase obtained above to the aqueous phase and stir at 60°C until homogeneous to obtain the mixture solution I.

[0106] Comparative Example 4

[0107] This embodiment is the fourth comparative example of the present invention. This comparative example provides an ascorbate glucoside collagen supramolecular solution I that was not prepared using the method of the present invention. The ascorbate glucoside collagen supramolecular solution I is prepared by the following method:

[0108] Weigh out 15 parts of chloroform and 1 part of dicosyldimethylammonium chloride, mix them and heat to a set temperature of 60°C, stir to dissolve and mix thoroughly to obtain the oil phase.

[0109] Weigh out 10 parts of soluble collagen, 5 parts of ascorbate glucoside, 10 parts of glycerol and water (make up to 100 parts of the aqueous phase system), mix them to the set temperature of 60°C, stir and dissolve thoroughly to obtain the aqueous phase.

[0110] The oil phase obtained above was added to the aqueous phase and sheared at high speed for 2 minutes at 12,000 rpm to obtain the collagen supramolecular carrier promulgation. The promulgation obtained above was subjected to high-pressure homogenization at 800 bar and cyclicated 5 times to obtain supramolecular solution I, which contains collagen supramolecular bodies loaded with ascorbate glucoside.

[0111] Example 6

[0112] This embodiment is a test embodiment of the present invention, including:

[0113] 6.1 Appearance Test

[0114] The blank collagen supramolecular solution prepared in Example 1 was photographed, as shown below. Figure 1 As shown.

[0115] The blank collagen supramolecular solution obtained in Example 1 was diluted with distilled water, and the sample was aspirated by capillary tube and blown onto a support grid. After staining and washing, and after drying, it was observed by transmission electron microscopy, and the results were photographed and recorded. The results are as follows: Figure 2 As shown.

[0116] 6.2 After diluting the product solutions obtained in Examples 1-5 and Comparative Examples 2-4, the particle size was determined using a nanoparticle size zeta potential analyzer (Anton Paar Co., Ltd., Litesizer 500).

[0117] The particle size test results of the collagen supramolecular bodies prepared in Examples 1-5 and Comparative Examples 2-4 are as follows: Figures 3-7 , Figures 8-10 As shown, the test data for Examples 1 to 5 and Comparative Examples 2 to 4 are shown in Table 1:

[0118] Table 1. Particle size determination results of Examples 1-5 and Comparative Examples 2-4

[0119]

[0120] The above experimental results show that the supramolecular carriers prepared using the raw materials and preparation method of this invention in Examples 1 to 5 have uniform particle sizes, all reaching the nanometer scale. Comparative Example 2 exhibits irregular particle sizes, indicating that the collagen raw material itself has an irregular morphology; Comparative Example 3 also exhibits irregular particle sizes, indicating that direct mixing of raw materials and excipients did not form collagen supramolecular bodies; Comparative Example 4 has larger supramolecular body particle sizes than those formed in Examples 1 to 5, indicating that the addition of matrine coconut oil ionic liquid, based on the preparation method of this invention, helps optimize the particle size of collagen supramolecular bodies.

[0121] 6.3 Appearance stability test

[0122] The collagen supramolecular solutions prepared in Examples 1-5 were each aliquoted into four portions and stored at 4°C, room temperature light exposure (RT), 45°C, and -25°C, respectively. Visual changes were photographed and recorded on the day of preparation (0) and 30 days later. The test results are as follows: Figure 11 As shown.

[0123] The results show that the supramolecular carrier of the present invention exhibits good appearance stability after one month of storage at 4°C, room temperature light irradiation (RT), 45°C, and -25°C, remaining clear and transparent before and after storage. In contrast, the collagen supramolecular solution prepared in Comparative Example 4 showed obvious white precipitate after 30 days of storage at room temperature, indicating significantly inferior stability compared to the collagen supramolecular prepared using the raw materials and preparation method of this application. These experimental results further demonstrate that the addition of matrine coconut oil ionic liquid during the preparation process can significantly improve the thermodynamic stability of the collagen supramolecular.

[0124] 6.4 Encapsulation Efficiency Stability Determination

[0125] 6.4.1 HPLC Detection Method

[0126] Testing instrument: Liquid chromatograph: Agilent 1260 Infinity II;

[0127] Chromatographic conditions: Agilent TC-C18 column (4.6 mm × 250 mm, 5 μm); mobile phase: 0.2% acetic acid aqueous solution (pH = 3.1): methanol = 90:10; flow rate: 1 mL / min; detection wavelength: 255 nm; column temperature: 30 °C; injection volume: 20 μL.

[0128] Standard curve establishment: An appropriate amount of ascorbic acid glucoside was weighed into a brown volumetric flask, dissolved in pure water, and diluted to volume to prepare solutions with concentration gradients of 1, 2, 5, 10, 20, 50, 100, 200, and 500 μg / ml. These solutions were then detected by HPLC. The results showed that the linear fitting equation was y = 14.16x + 2.3053(R²). 2 =1), and the linear relationship is good in the range of 1 to 500 μg / mL.

[0129] 6.4.2 Encapsulation efficiency determination

[0130] The Sephadex G50 gel column (1.5cm*30cm) was packed using standard methods. 0.2ml of sample solution was loaded onto the column, eluted with water, and collected in fractions. Free drug was determined using the HPLC detection method described in 6.4.1 above, according to (W... 总 -W 游离 ) / W 总 *100% Encapsulation rate is calculated.

[0131] The sample solutions included the collagen supramolecular solution prepared in Example 4 and supramolecular solution I prepared in Comparative Example 4. Both sample solutions were stored for 30 days at 4°C, room temperature light exposure (RT), 45°C, and -25°C, respectively. Changes in encapsulation efficiency were observed before and after storage. The test results for the sample solution in Example 4 are as follows: Figure 12 As shown, the test results of the sample solution in Comparative Example 4 are as follows: Figure 13 As shown.

[0132] The results above show that on the day of preparation, the encapsulation rate of Example 4 was significantly higher than that of Comparative Example 4, and the encapsulation rate decreased after being placed under high temperature conditions for 30 days. The encapsulation rate of collagen supramolecular bodies in Example 4 decreased slightly under high temperature conditions, especially at 45°C, where the encapsulation rate dropped to 89.2%. However, overall, the encapsulation rate of collagen supramolecular bodies of the present invention remained relatively stable for one month.

[0133] 6.5 Particle size stability test

[0134] The collagen supramolecular solution prepared in Example 4 and the supramolecular solution I prepared in Comparative Example 4 were placed at 4°C, room temperature light irradiation (RT), 45°C, and -25°C, respectively. The particle size changes were measured on the day of preparation (0 represents 0) and 30 days later. The test results of the sample solution in Example 4 are as follows: Figure 14 As shown, the test results of the sample solution in Comparative Example 4 are as follows: Figure 15 As shown in the figure. The experimental results above indicate that the collagen supramolecular particles loaded with active ingredients prepared using the method of this invention exhibit good thermodynamic stability within one month, which is superior to that of Comparative Example 4.

[0135] 6.6 Detection of the Permeation-Enhancing Effect of Collagen Supramolecular Bodies

[0136] 6.6.1 Method for detecting skin retention

[0137] This experiment set up one experimental group and three control groups. The experimental group used the collagen supramolecular solution loaded with ascorbate glucoside prepared in Example 4 as the test sample, while the three control groups used the ascorbate glucoside solution prepared in Comparative Example 1, the mixture solution I prepared in Comparative Example 3, and the supramolecular solution I prepared in Comparative Example 4 as the test samples, respectively. Both the experimental group and the control group were set up with three replicates, and the experimental results were averaged.

[0138] Before the experiment, a pigskin model with a thickness of 300±50 μm was prepared using a skin grafting scalpel. This model was then cut into small circular pieces the size of the receiving pool and placed in physiological saline for later use. Phosphate buffer (pH=7.4) was used as the receiving medium. During the experiment, the pigskin model was fixed between the release pool and the receiving pool, with the stratum corneum side facing the release pool and the dermis side facing the receiving pool, ensuring close contact between the skin and the receiving solution, and preventing air bubbles from forming. A certain amount of test sample was then added to the surface of the pigskin model. During this process, the temperature of the receiving pool was maintained at 37±0.5℃, and a magnetic stir bar was placed inside the receiving pool, rotating at 300 rpm throughout the experiment.

[0139] Eight hours after the in vitro transdermal treatment, the pig skin model was removed, and the residual solution on the surface was cleaned with pure water. Skin from the transdermal site was taken, minced, and homogenized with 1.5 ml of pure water. The homogenate was sonicated for 1 hour to extract ascorbate glucoside from the skin. The homogenate was transferred to a centrifuge tube, vortexed, and centrifuged at 12,000 rpm for 10 minutes. The residue was extracted again with 1 ml of pure water. The two supernatants were combined, mixed, and the supernatant was filtered through a 0.22 μm filter membrane. The ascorbate glucoside content in the supernatant was analyzed according to the HPLC detection method provided in 6.4.1 above, thus obtaining the transdermal retention of collagen ascorbate glucoside supramolecular solution and ascorbate glucoside solution.

[0140] 6.5.2 Results of skin retention measurement

[0141] The experimental results are shown in Figure 16. There was no significant difference in skin retention between Comparative Example 1 and Comparative Example 3. The retention of Comparative Example 4 was 2.6 times that of Comparative Example 1, indicating that in Comparative Example 4, the skin penetration effect was better than that of Comparative Example 1 and Comparative Example 3, which did not form collagen supramolecular bodies, by forming AA2G collagen supramolecular bodies.

[0142] Furthermore, the skin retention of ascorbate glucoside in Example 4 was 4.0 times that of Comparative Example 1 and 1.5 times that of Comparative Example 3, indicating that the collagen supramolecular bodies prepared by adding matrine coconut oil ionic liquid are more effective in promoting the penetration of active ingredients than those prepared without adding matrine coconut oil ionic liquid.

[0143] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention. Technical aspects, shapes, and structures not described in detail in this invention are all well-known technologies.

Claims

1. A collagen supramolecular body, characterized in that, It is prepared from the following raw materials in parts by weight: 0.5-10 parts collagen, 0.1-10 parts stabilizer selected from any one or more of myristyltrimethylammonium bromide, stearyltrimethylammonium bromide, lauryltrimethylammonium bromide, discoyldimethylammonium chloride, and distearyldimethylammonium chloride, 5-25 parts alcohol solvent selected from any one or more of ethanol, propylene glycol, butylene glycol, pentanediol, or hexanediol, 2-10 parts glycerol, 0.1-4 parts ionic liquid of matrine coconut oil ionic liquid, and 7-1000 parts water. The preparation method of collagen supramolecular bodies includes the following steps: S1: Prepare an aqueous phase and an oil phase separately. The oil phase includes an alcohol solvent, a stabilizer, and an ionic liquid. Mix them at 40-60°C. The aqueous phase includes collagen, glycerol, and water. Mix them at 40-60°C. S2: The above aqueous phase and oil phase are mixed and a primary emulsion is prepared by high-speed shearing. The high-speed shearing time is 1 to 5 minutes and the high-speed shearing speed is 5000 to 12000 rpm. S3: The above colostrum is subjected to high-pressure homogenization at 300-800 bar and cycled 3-8 times to prepare a collagen supramolecular solution, wherein the collagen supramolecular solution contains collagen supramolecular bodies.

2. The collagen supramolecular body as described in claim 1, characterized in that: The collagen supramolecular body serves as a carrier for loading active ingredients.

3. The collagen supramolecular body as described in claim 2, characterized in that: The active ingredient is any one or more of skin care active ingredients or pharmaceutical active ingredients.

4. A collagen supramolecular body as described in claim 1, characterized in that: The collagen is any one of collagen extract, hydrolyzed collagen, soluble collagen, deer bone collagen, protoplasmic collagen, and recombinant type III human collagen.

5. The method for preparing a collagen supramolecular body as described in claim 1, characterized in that, Includes the following steps: S1: Prepare an aqueous phase and an oil phase separately. The oil phase includes an alcohol solvent, a stabilizer, and an ionic liquid. Mix them at 40-60°C. The aqueous phase includes collagen, glycerol, and water. Mix them at 40-60°C. S2: The above aqueous phase and oil phase are mixed and a primary emulsion is prepared by high-speed shearing. The high-speed shearing time is 1 to 5 minutes and the high-speed shearing speed is 5000 to 12000 rpm. S3: The above colostrum is subjected to high-pressure homogenization at 300-800 bar and cycled 3-8 times to prepare a collagen supramolecular solution, wherein the collagen supramolecular solution contains collagen supramolecular bodies.

6. The application of a collagen supramolecular body as described in any one of claims 1 to 4 in the preparation of food, cosmetics, or feed.

7. The use of a collagen supramolecular body as described in any one of claims 1 to 4 in the preparation of a pharmaceutical carrier for human or animal use.

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