Targeted transdermal anti-aging preparation based on CRTF kinetic element

Abstract

The invention provides a targeted transdermal anti-aging preparation based on CRTF kinetic energy elements. The preparation comprises the following active components: 1-50 parts by mass of a CRTF kinetic energy element complex; 100 to 300 parts by mass of PLGA microspheres; the bionic penetration enhancer is prepared from ceramide, cholesterol and linoleic acid according to the mass ratio of 1 to (0.6 to 0.8) to (0.2 to 0.4); and 50-150 parts by mass of a humectant. Through the collaborative design of the CRTF kinetic energy complex and the PLGA microspheres and in combination with the precise proportion of the bionic penetration enhancer, the efficient transdermal delivery, long-acting slow release and targeting effects of anti-aging components are achieved, and the bioavailability of active components and the skin anti-aging effect are remarkably improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine and medical aesthetic materials, and specifically relates to a targeted transdermal anti-aging preparation based on CRTF kinetic energy. Background Art

[0002] Skin aging is the most visible manifestation of aging in the human body, primarily manifested by wrinkle growth, decreased elasticity, and hyperpigmentation. Its core mechanisms involve dermal collagen loss, increased oxidative stress, and extracellular matrix degradation. Current anti-aging agents fall into three main categories: topical skincare products, injectable fillers, and phototherapy devices, but all have significant limitations.

[0003] Topical skincare products typically rely on active ingredients like retinol, peptides, or hyaluronic acid. However, substances with a molecular weight exceeding 500 Da have difficulty penetrating the stratum corneum, and their bioavailability is generally less than 10%. Existing technologies attempt to enhance permeability through liposome encapsulation or nanoemulsification, such as the use of hyaluronic acid-modified liposome drug delivery systems. However, these carriers suffer from poor stability at room temperature, are prone to drug leakage, and have drug loading limited to 5-6%. Furthermore, traditional formulations lack targeting, acting only on the epidermis and failing to precisely deliver to dermal fibroblasts.

[0004] While injectable fillers like collagen or hyaluronic acid can directly replenish the dermal matrix, they are invasive treatments, carry risks of redness, swelling, and infection, and their effects only last for 3-6 months. The recent emergence of microneedle transdermal technology promotes drug penetration through physical puncture, but it can disrupt the skin's barrier function, leading to redness or scaling in people with sensitive skin.

[0005] Photoelectric devices such as radiofrequency or lasers promote collagen regeneration through thermal stimulation, but their energy penetration depth is limited. Traditional radiofrequency can only reach the mid-to-superior dermis, resulting in a thermal efficiency loss of over 30%. Emerging transdermal collagen light technology utilizes 760-1940nm composite infrared light waves, which can penetrate 4.5mm below the skin. However, the equipment requires professional operation, and in home use, insufficient power can lead to slow results.

[0006] In terms of active ingredient compounding, existing technologies mostly use single ingredients or simple combinations, such as combining vitamin C with palmitoyl tripeptide. However, differences in pH can lead to component leaching. Some studies have attempted to enhance the efficacy of antioxidants, such as combining GPX4 agonists with 15-LOX inhibitors. However, gingerols are easily metabolized by the sebaceous glands during transdermal delivery, and the actual concentration reaching the dermis is less than 1%. The design of transdermal carrier systems also faces challenges. While PLGA microspheres can achieve sustained release, the drug release rate drops sharply by 50% when the porosity falls below 30%. While liposomes have good skin compatibility, traditional preparation methods only achieve an encapsulation efficiency of 50-60%, and the stability of the biomimetic lipid membrane is significantly reduced when the cholesterol:ceramide mass ratio deviates from 1:0.7. Existing penetration enhancers such as azone can cause irritation, and the extraction process for natural ceramides is complex, with the yield of rice bran oil-derived phytosphingosine ceramide less than 20%.

[0007] Considering the shortcomings of existing technologies, an ideal anti-aging preparation must simultaneously meet the following conditions: first, achieve small molecule size, ensuring that the molecular weight of the active ingredient is less than 500Da to penetrate the stratum corneum; second, construct a temperature-responsive delivery system that triggers release at a skin surface temperature of 32°C; third, have a precise compounding ratio, such as a 1:0.7:0.3 ratio of ceramide-cholesterol-linoleic acid to simulate the natural lipid structure; and fourth, combine phototherapy with chemical penetration enhancement, such as using near-infrared long waves to enhance microcirculation while using liposomes to open intercellular channels. These requirements are precisely the core issues that this patented technical solution aims to address. Therefore, it is necessary to design a targeted transdermal anti-aging preparation based on CRTF kinetic energy. Summary of the Invention

[0008] In order to overcome the defects in the prior art, a targeted transdermal anti-aging preparation based on CRTF kinetic energy is provided.

[0009] In order to achieve the above object, the present invention provides the following technical solutions: A targeted transdermal anti-aging preparation based on CRTF kinetic energy, which contains the following active ingredients: 1-50 parts by weight of CRTF kinetic energy complex; 100-300 parts by mass of PLGA microspheres; 30-80 parts by weight of a biomimetic penetration enhancer, wherein the biomimetic penetration enhancer is composed of ceramide, cholesterol, and linoleic acid in a mass ratio of 1:0.6-0.8:0.2-0.4; 50-150 parts by mass of moisturizing agent.

[0010] The method for preparing the CRTF kinetic energy complex comprises the following steps: a raw material processing: Take 100 parts by mass of deep-sea fish cartilage, crushed and mixed with 200 parts by mass of 0.1M sodium citrate buffer, stirred at 3-5 ℃ for 12-24 hours to obtain a cartilage suspension; b. Enzymatic reaction: Add 2-3 parts by mass of trypsin and 5-7 parts by mass of collagenase to the cartilage suspension obtained in the previous step, incubate at 36-38°C for 4-8 hours, and centrifuge to obtain the supernatant; c. Ultrafiltration purification: Using a 10kDa ultrafiltration membrane to retain collagen fragments with a molecular weight cutoff of less than 1kDa, the collagen fragment powder was obtained after lyophilization; d. Amide bond coupling: Collagen fragments and phytosphingosine were mixed at a mass ratio of 2:3, and EDC / NHS catalyst was added. The mixture was reacted at 20-30°C for 12-36 hours. After dialysis, the mixture was lyophilized to obtain the CRTF kinesin complex.

[0011] The encapsulation efficiency of the PLGA microspheres is 90-95%, and the drug loading is 8-12 parts by mass per 100 parts by mass of the microspheres. The in vitro release curve of the PLGA microspheres satisfies the following requirements: a burst release rate of less than 15% within 6 hours and a cumulative release rate of greater than 80% within 72 hours.

[0012] The preparation method of the PLGA microspheres comprises the following steps: a colostrum preparation: 100 parts by mass of PLGA was dissolved in 200-300 parts by mass of dichloromethane, 50-70 parts by mass of an aqueous solution of the CRTF complex was added, and the mixture was homogenized to form a W / O emulsion at a homogenization speed of 8000-10000 rpm for 3-5 minutes; b emulsion curing: The W / O emulsion obtained in the previous step was added dropwise to 500-600 parts by mass of a 0.5% aqueous solution of polyvinyl alcohol, stirred at a speed of 800-1000 rpm, the curing time was 4-6 hours, and the microspheres were collected by centrifugation; c. Drying and Sieving: The microspheres obtained in the previous step are vacuum dried and sieved to obtain microspheres with a particle size of 50-100 μm, thereby obtaining 120-150 parts by weight of PLGA microspheres.

[0013] The liposome particle size in the liposome suspension is 100-200 nm, and the zeta potential is -20 to -30 mV.

[0014] The preparation method of the biomimetic penetration enhancer comprises the following steps: a melt mixing: 10 parts by mass of ceramide and 6-8 parts by mass of cholesterol were melted at 65 ° C, 2-4 parts by mass of linoleic acid were added and stirred until uniform to obtain a liquid lipid mixture; b. Liposome formation: Cool to 40°C, inject 50 parts by weight of phosphate buffer with a pH of 6.0, and sonicate at a power of 100 W for 10 minutes to obtain 60-70 parts by weight of a liposome suspension.

[0015] The moisturizing agent includes glycerin and sodium hyaluronate, and the mass ratio of the glycerin to the sodium hyaluronate is 2-4:1.

[0016] The preparation further comprises 2-10 parts by mass of a buffer; the buffer is a citric acid-disodium hydrogen phosphate buffer with a pH value of 5.5-6.5.

[0017] The preparation also contains rejuvenation kinetic energy, which includes 1-3 parts by mass of sodium hyaluronate, 0.5-1 parts by mass of ascorbyl glucoside, 0.5-1 parts by mass of folic acid, 0.05-0.4 parts by mass of vitamin B12, 0.2-0.4 parts by mass of calcium chloride, 0.2-0.4 parts by mass of potassium chloride, 0.1-0.3 parts by mass of adenosine, 0.1-0.3 parts by mass of adenosine triphosphate, 0.1-0.3 parts by mass of aminobutyric acid, 0.1-0.3 parts by mass of alanine, 0.1-0.3 parts by mass of flavin adenine dinucleotide disodium, 0.1-0.3 parts by mass of nicotinamide adenine dinucleotide, 0.1-0.3 parts by mass of glutathione, and 0.2-0.6 parts by mass of glucose.

[0018] The preparation further comprises 0.05-0.1 parts by mass of an antioxidant, wherein the antioxidant is one of tocopherol acetate, astaxanthin, and coenzyme Q10.

[0019] Compared with the prior art, the advantages and beneficial effects of the present invention are: 1. The formulation of this application significantly enhances the transdermal efficiency and targeting of anti-aging ingredients through the synergistic effect of the CRTF kinetic energy complex and PLGA microspheres. Collagen fragments produced by enzymatic hydrolysis of deep-sea fish cartilage are coupled to phytosphingosine via amide bonds to form an amphiphilic small molecule complex. This structure can mimic skin extracellular matrix signals and activate the collagen synthesis pathway in fibroblasts. Furthermore, the molecular weight of the collagen fragments in the complex is controlled within the range of 1-10 kDa, ensuring that they can penetrate the stratum corneum without being degraded.

[0020] 2. PLGA microspheres are prepared using a W / O / W emulsion method. By adjusting the polyvinyl alcohol concentration and curing time, a porous structure is formed on the microsphere surface. This design intelligently controls the drug release rate upon contact with skin temperature. The three-dimensional network structure within the microspheres encapsulates the CRTF complex within the pores, preventing the active ingredient from being damaged by pepsin while achieving a sustained-release efficiency of over 80% within 72 hours. In vitro permeation experiments showed that the cumulative permeation of this drug delivery system in an isolated porcine skin model reached 3.2 times that of a conventional emulsion.

[0021] 3. The biomimetic penetration enhancer precisely blends ceramide, cholesterol, and linoleic acid in proportions that mimic the lipid composition of the human stratum corneum. These biomimetic liposomes, when ultrasonically treated at 40°C, form uniformly sized nanovesicles, whose bilayer structure is highly compatible with skin cell membranes. The biomimetic penetration enhancer can penetrate into the interstitial spaces between keratinocytes, temporarily widening the intercellular channels to 15-20 nm and creating favorable conditions for the transdermal penetration of the CRTF complex. Furthermore, linoleic acid, an essential fatty acid, repairs a damaged skin barrier and reduces transepidermal water loss by over 40%.

[0022] 4. The moisturizing system utilizes a complex formula of glycerin and sodium hyaluronate. Through the small molecule hygroscopicity of glycerin and the three-dimensional water-locking network of sodium hyaluronate, it creates a gradient moisturizing effect across the epidermis. After 28 days of use, this combination can increase stratum corneum water content by 35% without the stickiness associated with traditional hyaluronic acid formulations. A citric acid-phosphate buffer system maintains a slightly acidic pH of 5.5-6.5, further enhancing the skin's microecological balance.

[0023] 5. The antioxidant module utilizes a synergistic combination of tocopheryl acetate and coenzyme Q10. The former targets the lipid layer of cell membranes to block free radical chain reactions, while the latter promotes ATP synthesis within mitochondria. This dual protective mechanism increases the DPPH free radical scavenging rate to 92%, far exceeding the effectiveness of either component alone. This system effectively inhibits UV-induced collagen cross-linking.

[0024] 6. This application also integrates the combined action mechanism of physical and chemical penetration enhancement. PLGA microspheres achieve long-term release through passive diffusion, while biomimetic liposomes actively pry open the stratum corneum channels. The combination of the two significantly increases the transdermal rate of active ingredients without causing skin irritation. This targeted delivery feature enables the CRTF complex to precisely act on dermal fibroblasts, significantly improving the efficiency of collagen regeneration.

[0025] 7. This preparation achieves anti-aging effects by combining multiple kinetic ingredients, synergistically working from multiple dimensions, including cellular energy metabolism, antioxidant repair, and barrier strengthening. Sodium hyaluronate serves as the core carrier, and its three-dimensional network structure can lock in moisture and form a transdermal delivery channel. The ionic balance created with calcium chloride and potassium chloride maintains cell membrane stability while promoting the penetration of active ingredients. Ascorbyl glucoside is hydrolyzed by α-glucosidase in the skin's surface layer to release prototype vitamin C. This whitens skin by reducing the melanin intermediate dopaquinone, stimulates the expression of collagen synthase, and works with folic acid to regulate the epidermal cell differentiation cycle, reducing wrinkle formation.

[0026] 8. The adenosine and adenosine triphosphate added in this application constitute an energy transfer system, directly replenishing the ATP required for cell metabolism and activating the proliferation capacity of skin fibroblasts. It can increase collagen secretion and alleviate the decrease in mitochondrial membrane potential caused by ultraviolet rays. Nicotinamide adenine dinucleotide, as a precursor of coenzyme I, participates in redox reactions and forms an antioxidant cascade reaction with glutathione, neutralizing free radicals while regenerating vitamin E, thereby blocking the photoaging chain. Flavin adenine dinucleotide disodium regulates NADPH oxidase activity, reduces the release of the inflammatory factor IL-6, and improves skin redness and sensitivity.

[0027] 9. The aminobutyric acid and alanine in this application act as neurotransmitter modulators, inhibiting muscle contraction caused by excessive release of acetylcholine and dynamically soothing expression lines. Glucose provides a glycolytic substrate, supporting the rapid renewal of keratinocytes. Its synergistic moisturizing effect with sodium hyaluronate has been tested to maintain skin hydration for more than 48 hours. This formula gradually releases the active ingredients on the weakly acidic skin surface through a microenvironment pH-responsive release mechanism, avoiding irritation caused by sudden release and significantly improving elastic fiber density. DETAILED DESCRIPTION

[0028] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0029] In this application, the models of various raw materials are briefly described as follows: A targeted transdermal anti-aging preparation based on CRTF kinetic energy, which contains the following active ingredients: 1-50 parts by weight of CRTF kinetic energy complex; 100-300 parts by mass of PLGA microspheres; 30-80 parts by weight of a biomimetic penetration enhancer, wherein the biomimetic penetration enhancer is composed of ceramide, cholesterol, and linoleic acid in a mass ratio of 1:0.6-0.8:0.2-0.4; 50-150 parts by mass of moisturizing agent.

[0030] The method for preparing the CRTF kinetic energy complex comprises the following steps: a raw material processing: Take 100 parts by mass of deep-sea fish cartilage, crushed and mixed with 200 parts by mass of 0.1M sodium citrate buffer, stirred at 3-5 ℃ for 12-24 hours to obtain a cartilage suspension; b. Enzymatic reaction: Add 2-3 parts by mass of trypsin and 5-7 parts by mass of collagenase to the cartilage suspension obtained in the previous step, incubate at 36-38°C for 4-8 hours, and centrifuge to obtain the supernatant; c. Ultrafiltration purification: Using a 10kDa ultrafiltration membrane to retain collagen fragments with a molecular weight cutoff of less than 1kDa, the collagen fragment powder was obtained after lyophilization; d. Amide bond coupling: Collagen fragments and phytosphingosine were mixed at a mass ratio of 2:3, and EDC / NHS catalyst was added. The mixture was reacted at 20-30°C for 12-36 hours. After dialysis, the mixture was lyophilized to obtain the CRTF kinesin complex.

[0031] The encapsulation efficiency of the PLGA microspheres is 90-95%, and the drug loading is 8-12 parts by mass per 100 parts by mass of the microspheres. The in vitro release curve of the PLGA microspheres satisfies the following requirements: a burst release rate of less than 15% within 6 hours and a cumulative release rate of greater than 80% within 72 hours.

[0032] The preparation method of the PLGA microspheres comprises the following steps: a colostrum preparation: 100 parts by mass of PLGA was dissolved in 200-300 parts by mass of dichloromethane, 50-70 parts by mass of an aqueous solution of the CRTF complex was added, and the mixture was homogenized to form a W / O emulsion at a homogenization speed of 8000-10000 rpm for 3-5 minutes; b emulsion curing: The W / O emulsion obtained in the previous step was added dropwise to 500-600 parts by mass of a 0.5% aqueous solution of polyvinyl alcohol, stirred at a speed of 800-1000 rpm, the curing time was 4-6 hours, and the microspheres were collected by centrifugation; c. Drying and Sieving: The microspheres obtained in the previous step are vacuum dried and sieved to obtain microspheres with a particle size of 50-100 μm, thereby obtaining 120-150 parts by weight of PLGA microspheres.

[0033] The liposome particle size in the liposome suspension is 100-200 nm, and the zeta potential is -20 to -30 mV.

[0034] The preparation method of the biomimetic penetration enhancer comprises the following steps: a melt mixing: 10 parts by mass of ceramide and 6-8 parts by mass of cholesterol were melted at 65 ° C, 2-4 parts by mass of linoleic acid were added and stirred until uniform to obtain a liquid lipid mixture; b. Liposome formation: Cool to 40°C, inject 50 parts by weight of phosphate buffer with a pH of 6.0, and sonicate at a power of 100 W for 10 minutes to obtain 60-70 parts by weight of a liposome suspension.

[0035] The moisturizing agent includes glycerin and sodium hyaluronate, and the mass ratio of the glycerin to the sodium hyaluronate is 2-4:1.

[0036] The preparation further comprises 2-10 parts by mass of a buffer solution, which is a citric acid-disodium hydrogen phosphate buffer solution with a pH value of 5.5-6.5.

[0037] The preparation also contains rejuvenation kinetic energy, which includes 1-3 parts by mass of sodium hyaluronate, 0.5-1 parts by mass of ascorbyl glucoside, 0.5-1 parts by mass of folic acid, 0.05-0.4 parts by mass of vitamin B12, 0.2-0.4 parts by mass of calcium chloride, 0.2-0.4 parts by mass of potassium chloride, 0.1-0.3 parts by mass of adenosine, 0.1-0.3 parts by mass of adenosine triphosphate, 0.1-0.3 parts by mass of aminobutyric acid, 0.1-0.3 parts by mass of alanine, 0.1-0.3 parts by mass of flavin adenine dinucleotide disodium, 0.1-0.3 parts by mass of nicotinamide adenine dinucleotide, 0.1-0.3 parts by mass of glutathione, and 0.2-0.6 parts by mass of glucose.

[0038] The preparation further comprises 0.05-0.1 parts by mass of an antioxidant, wherein the antioxidant is one of tocopherol acetate, astaxanthin, and coenzyme Q10.

[0039] The technical solution of the present invention is further illustrated by the following examples and comparative examples, but the protection scope of the present invention is not limited thereto.

[0040] Example 1 The targeted transdermal anti-aging preparation prepared in this example comprises the following components: 4 parts by mass of CRTF kinetic energy complex, 300 parts by mass of PLGA microspheres, 30 parts by mass of a biomimetic penetration enhancer (ceramide: cholesterol: linoleic acid = 1:0.7:0.3), and 100 parts by mass of a moisturizer (glycerol: sodium hyaluronate = 3:1).

[0041] Preparation of the CRTF kinetic energy complex: 100 parts by mass of deep-sea fish cartilage was ground and mixed with 200 parts by mass of 0.1M sodium citrate buffer. The mixture was stirred at 4°C for 18 hours. A mixture of 2.5 parts by mass of trypsin and 6 parts by mass of collagenase was added and reacted at 37°C for 6 hours. After ultrafiltration and lyophilization, the collagen fragments were coupled with phytosphingosine at a mass ratio of 2:3 and reacted at 25°C for 24 hours.

[0042] Preparation of PLGA microspheres: PLGA was dissolved in 250 parts by mass of dichloromethane, added with 60 parts by mass of CRTF aqueous solution, homogenized and emulsified (9000 rpm, 4 minutes), and added dropwise to 550 parts by mass of 0.5% polyvinyl alcohol aqueous solution for curing for 5 hours. After drying, 50-100 μm microspheres were sieved.

[0043] Preparation of biomimetic penetration enhancer: 10 parts by mass of ceramide and 7 parts by mass of cholesterol were melted at 65°C, 3 parts by mass of linoleic acid were added and stirred until homogeneous, and then cooled to 40°C and injected with 50 parts by mass of pH 6.0 phosphate buffer, and sonicated (100W, 10 minutes) to form a liposome suspension.

[0044] The preparation also contains rejuvenation kinetic energy, which includes 3 parts by mass of sodium hyaluronate, 0.5 parts by mass of ascorbyl glucoside, 0.5 parts by mass of folic acid, 0.05 parts by mass of vitamin B12, 0.2 parts by mass of calcium chloride, 0.4 parts by mass of potassium chloride, 0.3 parts by mass of adenosine, 0.3 parts by mass of adenosine triphosphate, 0.3 parts by mass of aminobutyric acid, 0.3 parts by mass of alanine, 0.3 parts by mass of flavin adenine dinucleotide disodium, 0.3 parts by mass of nicotinamide adenine dinucleotide, 0.3 parts by mass of glutathione, and 0.2 parts by mass of glucose.

[0045] Example 2 The same points as in Example 1 are not described in detail here, and the differences are as follows: The components of this embodiment are adjusted as follows: 25 parts by mass of CRTF kinetic energy complex, 200 parts by mass of PLGA microspheres, 55 parts by mass of biomimetic penetration enhancer (ceramide: cholesterol: linoleic acid = 1:0.6:0.2), and 50 parts by mass of moisturizer (glycerol: sodium hyaluronate = 4:1).

[0046] Preparation of CRTF complex: Stir at 5°C for 12 hours, add 3 parts by mass of trypsin and 7 parts by mass of collagenase, react at 38°C for 8 hours, and perform coupling reaction at 20°C for 12 hours.

[0047] Preparation of PLGA microspheres: PLGA was dissolved in 300 parts by weight of dichloromethane, and 70 parts by weight of CRTF aqueous solution was added, homogenized (8000 rpm, 5 minutes), and cured for 4 hours.

[0048] Preparation of biomimetic penetration enhancer: 10 parts by mass of ceramide and 6 parts by mass of cholesterol were melted, 2 parts by mass of linoleic acid were added, and pH 6.0 buffer was injected and ultrasonic treatment was performed to form liposomes.

[0049] The preparation also contains rejuvenation kinetic energy, which includes 2 parts by mass of sodium hyaluronate, 1 part by mass of ascorbyl glucoside, 1 part by mass of folic acid, 0.3 parts by mass of vitamin B12, 0.4 parts by mass of calcium chloride, 0.2 parts by mass of potassium chloride, 0.1 parts by mass of adenosine, 0.1 parts by mass of adenosine triphosphate, 0.1 parts by mass of aminobutyric acid, 0.1 parts by mass of alanine, 0.1 parts by mass of flavin adenine dinucleotide disodium, 0.1 parts by mass of nicotinamide adenine dinucleotide, 0.1 parts by mass of glutathione, and 0.4 parts by mass of glucose.

[0050] Example 3 The same points as in Example 1 are not described in detail here, and the differences are as follows: This example uses intermediate parameters: 50 parts by mass of CRTF kinetic energy complex, 100 parts by mass of PLGA microspheres, 80 parts by mass of biomimetic penetration enhancer (ceramide: cholesterol: linoleic acid = 1:0.8:0.4), and 150 parts by mass of moisturizer (glycerol: sodium hyaluronate = 2:1).

[0051] Preparation of CRTF complex: Stir at 3°C ​​for 24 hours, react with 2 parts by mass of trypsin and 5 parts by mass of collagenase at 36°C for 4 hours, and perform coupling reaction at 30°C for 36 hours.

[0052] Preparation of PLGA microspheres: PLGA was dissolved in 200 parts by mass of dichloromethane, and 50 parts by mass of CRTF aqueous solution was added, homogenized (10,000 rpm, 3 minutes), and cured for 6 hours.

[0053] Preparation of biomimetic penetration enhancer: 10 parts by mass of ceramide and 8 parts by mass of cholesterol were melted, 4 parts by mass of linoleic acid were added, and pH 6.0 buffer was injected and then ultrasonicated to form liposomes.

[0054] The preparation also contains rejuvenation kinetic energy, which includes 1 mass part of sodium hyaluronate, 0.8 mass part of ascorbyl glucoside, 0.7 mass part of folic acid, 0.4 mass part of vitamin B12, 0.3 mass part of calcium chloride, 0.3 mass part of potassium chloride, 0.2 mass part of adenosine, 0.2 mass part of adenosine triphosphate, 0.2 mass part of aminobutyric acid, 0.2 mass part of alanine, 0.2 mass part of flavin adenine dinucleotide disodium, 0.2 mass part of nicotinamide adenine dinucleotide, 0.2 mass part of glutathione, and 0.6 mass part of glucose.

[0055] Comparative Example 1

[0056] The same points as in Example 1 are not described in detail here, and the differences are as follows: PLGA microspheres were not used and ordinary liposomes were used instead.

[0057] Comparative Example 2

[0058] The same points as in Example 2 are not described in detail here, and the differences are as follows: The ratio of biomimetic penetration enhancer was changed to 1:1:1.

[0059] Comparative Example 3

[0060] The same points as in Example 3 are not described in detail here, and the differences are as follows: The CRTF complex is not coupled to phytosphingosine.

[0061] Comparative Example 4

[0062] The same points as in Example 1 are not described in detail here, and the differences are as follows: The only moisturizer used is glycerin.

[0063] Comparative Example 5

[0064] The same points as in Example 1 are not described in detail here, and the differences are as follows: Ordinary PLGA microspheres are used, with a porosity of less than 30%.

[0065] Test results and analysis

[0066] The preparations of each embodiment and comparative example were analyzed and tested according to relevant standards. By comparing the data of the embodiments and comparative examples, it can be seen that the technical solution of the present invention has significant advantages in many aspects. The specific results are shown in Table 1.

[0067] Table 1 Test results

[0068] The high release rates of Examples 1-3 are compared with Comparative Examples 1 and 5, confirming the contribution of porous PLGA microspheres to sustained release. When the porosity is greater than 30%, the drug release kinetics conform to the zero-order equation. Comparative Example 2 shows that deviation from the 1:0.7:0.3 ratio will lead to a decrease in lipid membrane stability. The absolute value of the Zeta potential of Example 3 drops from -25mV to -15mV, and the transdermal efficiency decreases sharply. Comparative Example 3 verifies the necessity of phytosphingosine coupling - its hydrophobic chain can anchor collagen fragments to the fibroblast membrane, thereby upregulating the collagen synthesis signaling pathway by 2.1 times. Comparative Example 4 shows that the three-dimensional network structure of sodium hyaluronate can prolong the moisturizing time of glycerol, and the transepidermal water loss rate (TEWL) is 42% lower than that of single glycerol.

[0069] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A targeted transdermal anti-aging preparation based on CRTF kinetic energy, characterized in that: This preparation contains the following active ingredients: 1-50 parts by weight of CRTF kinetic energy complex; 100-300 parts by mass of PLGA microspheres; 30-80 parts by weight of a biomimetic penetration enhancer, wherein the biomimetic penetration enhancer is composed of ceramide, cholesterol, and linoleic acid in a mass ratio of 1:0.6-0.8:0.2-0.4; 50-150 parts by mass of moisturizing agent.

2. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The method for preparing the CRTF kinetic energy complex comprises the following steps: a raw material processing: Take 100 parts by mass of deep-sea fish cartilage, crushed and mixed with 200 parts by mass of 0.1M sodium citrate buffer, stirred at 3-5 ℃ for 12-24 hours to obtain a cartilage suspension; b. Enzymatic reaction: Add 2-3 parts by mass of trypsin and 5-7 parts by mass of collagenase to the cartilage suspension obtained in the previous step, incubate at 36-38°C for 4-8 hours, and centrifuge to obtain the supernatant; c. Ultrafiltration purification: Using a 10kDa ultrafiltration membrane to retain collagen fragments with a molecular weight cutoff of less than 1kDa, the collagen fragment powder was obtained after lyophilization; d. Amide bond coupling: Collagen fragments and phytosphingosine were mixed at a mass ratio of 2:3, and EDC / NHS catalyst was added. The mixture was reacted at 20-30°C for 12-36 hours. After dialysis, the mixture was lyophilized to obtain the CRTF kinesin complex.

3. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The encapsulation efficiency of the PLGA microspheres is 90-95%, and the drug loading is 8-12 parts by mass per 100 parts by mass of the microspheres. The in vitro release curve of the PLGA microspheres satisfies the following requirements: a burst release rate of less than 15% within 6 hours and a cumulative release rate of greater than 80% within 72 hours.

4. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 3, characterized in that: The preparation method of the PLGA microspheres comprises the following steps: a colostrum preparation: 100 parts by mass of PLGA was dissolved in 200-300 parts by mass of dichloromethane, 50-70 parts by mass of an aqueous solution of the CRTF complex was added, and the mixture was homogenized to form a W / O emulsion at a homogenization speed of 8000-10000 rpm for 3-5 minutes; b emulsion curing: The W / O emulsion obtained in the previous step was added dropwise to 500-600 parts by mass of a 0.5% aqueous solution of polyvinyl alcohol, stirred at a speed of 800-1000 rpm, the curing time was 4-6 hours, and the microspheres were collected by centrifugation; c. Drying and Sieving: The microspheres obtained in the previous step are vacuum dried and sieved to obtain microspheres with a particle size of 50-100 μm, thereby obtaining 120-150 parts by weight of PLGA microspheres.

5. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The liposome particle size in the liposome suspension is 100-200 nm, and the zeta potential is -20 to -30 mV.

6. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 5, characterized in that: The preparation method of the biomimetic penetration enhancer comprises the following steps: a melt mixing: 10 parts by mass of ceramide and 6-8 parts by mass of cholesterol were melted at 65 ° C, 2-4 parts by mass of linoleic acid were added and stirred until uniform to obtain a liquid lipid mixture; b. Liposome formation: Cool to 40°C, inject 50 parts by weight of phosphate buffer with a pH of 6.0, and sonicate at a power of 100 W for 10 minutes to obtain 60-70 parts by weight of a liposome suspension.

7. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that : The moisturizing agent includes glycerin and sodium hyaluronate, and the mass ratio of the glycerin to the sodium hyaluronate is 2-4:

1.

8. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The preparation further comprises 2-10 parts by mass of a buffer; the buffer is a citric acid-disodium hydrogen phosphate buffer with a pH value of 5.5-6.

5.

9. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The preparation also contains rejuvenation kinetic energy, which includes 1-3 parts by mass of sodium hyaluronate, 0.5-1 parts by mass of ascorbyl glucoside, 0.5-1 parts by mass of folic acid, 0.05-0.4 parts by mass of vitamin B12, 0.2-0.4 parts by mass of calcium chloride, 0.2-0.4 parts by mass of potassium chloride, 0.1-0.3 parts by mass of adenosine, 0.1-0.3 parts by mass of adenosine triphosphate, 0.1-0.3 parts by mass of aminobutyric acid, 0.1-0.3 parts by mass of alanine, 0.1-0.3 parts by mass of flavin adenine dinucleotide disodium, 0.1-0.3 parts by mass of nicotinamide adenine dinucleotide, 0.1-0.3 parts by mass of glutathione, and 0.2-0.6 parts by mass of glucose.

10. The targeted transdermal anti-aging preparation based on CRTF kinetic energy according to claim 1, characterized in that: The preparation further comprises 0.05-0.1 parts by mass of an antioxidant, wherein the antioxidant is one of tocopherol acetate, astaxanthin, and coenzyme Q10.

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