Transdermal absorption carrier, preparation method and application

Abstract

The invention discloses a transdermal absorption carrier as well as a preparation method and application thereof, and belongs to the technical field of cosmetic production. The invention solves the problem of how to develop an efficient and safe transdermal carrier. The composition is composed of the following components in percentage by mass: 2-5% of lucid ganoderma extract; 0.1 to 1 percent of glycine; 0.1 to 1% of cysteine; 0.1 to 1 percent of phenylalanine; 10 to 40 percent of polyhydric alcohol; and the balance of deionized water. According to the transdermal absorption carrier, the transdermal absorption efficiency of active ingredients of cosmetics is remarkably improved through the transmembrane effect of ganoderma lucidum polypeptide in the ganoderma lucidum extract and the synergistic effect of amino acid, and meanwhile, the transdermal absorption carrier has excellent biocompatibility and stability. The composition is suitable for essence, face cream and other dosage forms, and can carry vitamin C, nicotinamide, vitriol, collagen and other functional components.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetic production, and in particular relates to a transdermal absorption carrier, a preparation method and an application thereof. Background Art

[0002] Cosmetic penetration enhancement technology refers to a method of enhancing the transdermal absorption of active ingredients through physical, chemical or pharmaceutical means. Its core goal is to overcome the barrier effect of the skin's stratum corneum and ensure that the active ingredients reach an effective concentration in the target area and maintain a sufficient duration of action.

[0003] However, existing penetration enhancement technologies, such as liposomes, have a permeation rate of only 15-30% and may cause skin irritation. Chemical penetration enhancers, such as azone, damage the skin barrier. Therefore, the development of efficient and safe transdermal carriers is urgently needed. Summary of the Invention

[0004] In response to the problem of how to develop an efficient and safe transdermal carrier in the prior art, the present invention provides a transdermal absorption carrier, a preparation method and an application.

[0005] The technical solution adopted in the present invention is as follows: A transdermal absorption carrier, composed of the following components in percentage by mass: Ganoderma lucidum extract: 2-5%; Glycine: 0.1-1%; Cysteine: 0.1-1%; Phenylalanine: 0.1-1%; Polyols: 10-40%; The balance was deionized water.

[0006] After adopting this technical solution, Ganoderma lucidum extract is rich in Ganoderma lucidum peptides, which have multiple biological activities such as antioxidant, immunomodulatory, and anti-inflammatory properties. They can also penetrate the cell membrane barrier by interacting with the cell membrane and carry other active ingredients into the cell. Amino acids, as an important component of the skin's stratum corneum, have functions such as moisturizing and repairing the skin barrier. Combining Ganoderma lucidum peptides with specific amino acids mainly plays the following roles: 1. Promoting the binding of the carrier to the skin: Ganoderma lucidum peptides and amino acids themselves have good hydrophilicity and a certain degree of lipophilicity, which can better interact with lipids and water on the skin surface, improve the skin's barrier function, make the carrier fit more tightly to the skin, and facilitate more efficient delivery of the carried substances into the skin. 2. Increase skin permeability: Ganoderma lucidum peptides and amino acids can interact with proteins in the skin's stratum corneum, change the lipid structure between stratum corneum cells, increase the intercellular space, and make it easier for drugs or nutrients to pass through the stratum corneum, the main barrier of the skin, and enter the deeper layers of the skin. 3. Form temporary channels: They may form some temporary microscopic channels on the surface of the skin. These channels provide a more direct penetration path for the active ingredients carried, reducing the diffusion resistance of the active ingredients in the skin and thus promoting their transdermal absorption.

[0007] Specifically, the unique roles played by the three amino acids in this application are: Glycine: Molecular Structure: Glycine is the simplest amino acid, with a single hydrogen atom in its side chain. This makes the glycine molecule relatively small and highly polar. Because the amino (-NH2) and carboxyl (-COOH) groups are directly attached to the α-carbon atom, the overall molecule exhibits strong hydrophilicity.

[0008] Impact on permeability: Smaller molecular size makes it easier for them to penetrate tiny gaps in biological membranes, thus enhancing their permeability. Furthermore, their strong hydrophilicity allows them to form hydrogen bonds with water molecules, facilitating their diffusion in aqueous environments and potentially helping other substances to be transported more efficiently in aqueous environments.

[0009] Cysteine Molecular structure characteristics: Cysteine contains a unique group (-SH). In addition to amino and carboxyl groups, the sulfhydryl group gives cysteine some special chemical properties. The sulfhydryl group has high reactivity, and the molecular size of cysteine is moderate.

[0010] Impact on permeability: Sulfhydryl groups can interact with certain components of biological membranes (such as disulfide bonds in proteins) by forming new chemical bonds or altering the conformation of membrane proteins, potentially increasing membrane permeability and thus enhancing permeability. Furthermore, the moderate molecular size of cysteine allows it to maintain a certain degree of hydrophilicity while also possessing a certain degree of lipophilicity, potentially enabling it to better adapt to diverse biological membrane environments and providing advantages when crossing biological membranes.

[0011] Phenylalanine Molecular Structure: Phenylalanine contains a benzene ring side chain and belongs to the aromatic amino acid family. In addition to the amino (-NH2) and carboxyl (-COOH) groups common to all amino acids, attached to the α-carbon atom, the benzene ring imparts its unique physical and chemical properties. The benzene ring has a large conjugated structure, is relatively hydrophobic, and is bulky. This hydrophobicity stems from the relatively uniform distribution of the electron cloud formed by the covalent bonds between the carbon and hydrogen atoms in the benzene ring, lacking distinct polarity.

[0012] Impact on penetration-enhancing effect: The main component of biological membranes is the phospholipid bilayer, which has a lipophilic core. The benzene ring structure of phenylalanine gives it a certain lipophilicity, and has a good affinity with lipid membranes, allowing it to dissolve and diffuse through lipid membranes more easily. For example, during skin penetration, the lipid structure of the skin's stratum corneum has a certain permeability to lipophilic substances. Due to its benzene ring structure, phenylalanine is more likely to pass through the lipid region of the stratum corneum than some more hydrophilic amino acids (such as arginine and lysine), helping to carry other substances bound to it into the deep layers of the skin, showing good penetration-enhancing potential in this regard.

[0013] Preferably, the Ganoderma lucidum extract is derived from Ganoderma lucidum.

[0014] Preferably, the content of Ganoderma lucidum polypeptides with a molecular weight of 500-800 Da in the Ganoderma lucidum extract is 0.4%-1.5%.

[0015] A method for preparing a transdermal absorption carrier comprises the following steps: S1: Prepare raw materials according to the ratio; S2: Add the polyol to the solvent and stir until completely dissolved; S3: Add glycine, cysteine, and phenylalanine to the solution obtained in S2 in sequence, and stir until the amino acids are completely dissolved; S4: Add the Ganoderma lucidum extract to the solution obtained in S3, and stir until the mixture is uniform to obtain a transdermal absorption carrier.

[0016] Preferably, after stirring evenly, S4 further comprises adjusting the pH value to 4-7.

[0017] After adopting this technical solution, the pH value can be adjusted to 4-7 to stabilize the active ingredients.

[0018] Preferably, the preparation method of the Ganoderma lucidum extract comprises the following steps: S101: crushing the Ganoderma lucidum to obtain Ganoderma lucidum powder; S102: mixing the Ganoderma lucidum powder with a solvent to obtain a Ganoderma lucidum powder liquid; S103: raising the temperature of the Ganoderma lucidum powder liquid to 40° C. to 60° C. for extraction; S104: filtering and concentrating the extracted liquid; S105: aging the obtained concentrated solution at a temperature of 4° C.; S106: removing impurities from the aged concentrated solution, adding polyol, and mixing to obtain the Ganoderma lucidum extract.

[0019] The invention discloses an application of a transdermal absorption carrier as a raw material for cosmetic production.

[0020] Preferably, the cosmetics include essences, lotions, creams, masks and gels.

[0021] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are: The present invention combines Ganoderma lucidum polypeptide with specific amino acids, which can adjust the charge, stability and biocompatibility of the carrier, thereby enhancing the transdermal absorption effect. It is suitable for dosage forms such as essences and creams, and can carry effective ingredients such as vitamin C, niacinamide, proline, collagen, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Cumulative permeation curve. DETAILED DESCRIPTION

[0023] 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 in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative efforts shall fall within the scope of protection of this application.

[0024] Example 1 A transdermal absorption carrier, composed of the following components in percentage by mass: Ganoderma lucidum extract: 5%; Glycine: 0.3%; Cysteine: 0.4%; Phenylalanine: 0.8%; Butanediol: 30%; The balance was deionized water.

[0025] The preparation method is as follows: comprising the following steps: S1: Prepare a certain amount of raw materials according to the above formula, wherein the preparation method of Ganoderma lucidum extract is as follows: S101: Select high-quality Ganoderma lucidum fruiting bodies (Ganoderma lucidum), remove impurities, dry and crush them into appropriate particle sizes, generally preferably passing through a 40-100 mesh sieve. This can increase the contact area between the Ganoderma lucidum and water and improve the extraction efficiency. In this embodiment, the Ganoderma lucidum is crushed to a size that can pass through a 40-mesh sieve; S102: Adding Ganoderma lucidum powder into an extraction container, and adding deionized water at a mass ratio of Ganoderma lucidum powder to solvent of 1:10-15, stirring evenly to obtain Ganoderma lucidum powder liquid; S103: Heat the extraction container to raise the temperature of the Ganoderma lucidum powder solution to 40°C to 60°C for extraction. Maintain this temperature for 1 to 3 hours to prevent high temperatures from causing peptide denaturation and inactivation. Stir occasionally (at 50-100 rpm) to promote mass transfer and enhance extraction efficiency. Collect the liquid. Repeat this extraction process twice, and collect the liquid. S104: The combined feed solutions are filtered through a 1000-mesh nylon cloth for the first time. Citric acid or phosphate buffer may be added as appropriate to adjust the pH of the extract to within the range of 5.0-7.0. The extract is then concentrated by vacuum distillation at a relatively low temperature of 50°C to 60°C. The volume is fixed to a crude drug concentration of 0.1 g / mL to 0.3 g / mL, yielding a concentrate having a relative density of 1.05-1.15 (measured at 50°C to 60°C). S105: placing the concentrated solution after volume adjustment in a 4°C refrigerator for 5-7 days for aging; S106: The aged extract is centrifuged at 2200-2500 g (centrifuge model MK-20RB) to remove impurities. The collected filtrate is then passed through a 0.22 μm ultrafiltration membrane to remove suspended matter and macromolecular impurities. Butanediol is added to adjust the butanediol content to 25-40% (30% in this embodiment). The mixture is stirred and uniformly observed to be a transparent, uniform liquid. This yields a Ganoderma lucidum extract. HPLC confirms that the Ganoderma lucidum extract contains 0.4-1.5% Ganoderma lucidum polypeptides with a molecular weight of 500-800 Da.

[0026] S2: Add butanediol to deionized water and stir for 3-5 minutes under stirring (20-30 rpm) to form a homogeneous solution; S3: Add glycine, cysteine, and phenylalanine to the solution obtained in S2 in sequence, increase the stirring speed to (30-50 rpm), and continue for 15-20 minutes until completely dissolved; S4: Slowly add the Ganoderma lucidum extract to the solution obtained in S3. Reduce the stirring speed to 20-30 rpm and continue stirring for 30-40 minutes to ensure complete dissolution. Adjust the pH to 5.8 ± 0.2 with citric acid solution and measure the relative density of the solution (1.02 ± 0.01 g / mL).

[0027] In order to verify the effect of the transdermal absorption carrier provided by the present invention, the present invention conducted the following experiments (Note: The polypeptide content mentioned below refers to the content of Ganoderma lucidum polypeptide with a molecular weight of 500-800 Da): 1. Comparative experiment on transdermal efficiency Experimental design (1) Sample grouping: Experimental group: 5% of the transdermal absorption carrier obtained by the above method (the polypeptide content of the transdermal absorption carrier is 0.075%, and the total active ingredient content is 0.325%) is loaded with a 10% aqueous solution of bosine (the two can be mixed in proportion); Control group: 1% azone carrier (1% pure azone content) carrying 10% bosine aqueous solution; Blank group: 10% bosphorin aqueous solution.

[0028] (2) Transdermal model: A Franz diffusion cell (diffusion area 3.14 cm², pH 7.4 phosphate buffer as the receiving solution) was used, and excised pig ear skin (thickness 400 ± 20 μm) was used.

[0029] (3) Experimental conditions: The temperature was 37°C and the relative humidity was 65%. The receiving cell was stirred magnetically at 300 rpm and samples were taken at regular intervals (1, 2, 4, 6, and 8 h).

[0030] (4) Experimental results: The results are as follows Figure 1 As shown, from Figure 1 It can be seen that the cumulative permeation volume of the experimental group at 8 h was increased by 162.3% compared with the control group (p<0.01, two-tailed t-test) and by 633.1% compared with the blank group (p<0.001).

[0031] Stability testing (1) High temperature stability (40°C) Experimental method: A transdermal absorption carrier with a polypeptide content of 1.5% and a pH value of 5.84 was placed in an experimental environment at a temperature of 40°C for 30 days, and its polypeptide content, pH value and appearance were tested on different days.

[0032] Detection indicators: active ingredient (peptide content) retention rate (HPLC), pH value, appearance.

[0033] The results are shown in Table 1: Table 1

[0034] (2) Low temperature stability (-20°C) Experimental method: A transdermal absorption carrier with a polypeptide content of 1.5% and a pH value of 5.84 was placed in an experimental environment at a temperature of -20°C for 30 days.

[0035] Detection indicators: After thawing after 30 days of storage, there is no crystal precipitation of the carrier and the polypeptide content changes by ≤5%.

[0036] The results are shown in Table 2: Table 2

[0037] From the data in Tables 1 and 2, it can be seen that the transdermal absorption carrier provided by the present invention has an active ingredient retention rate of >90% under low and high temperature conditions for 30 days, has good high and low temperature resistance, and thus has good stability.

[0038] 3. Safety Assessment Human patch test Sample size: 30 healthy volunteers (half male and half female, aged 18-45 years).

[0039] Methods: The vehicle was applied to the inner forearm and occluded for 48 h before assessing skin reactions (according to ISO 10993-10).

[0040] The results are shown in Table 3: Table 3

[0041] Currently, the most common amino acids are lysine (isoelectric point 9.74), arginine (isoelectric point 10.76), histidine (isoelectric point 7.59), alanine (isoelectric point 6.00), proline (isoelectric point 6.30), glycine (isoelectric point 5.97), cysteine (isoelectric point 5.05), and phenylalanine (isoelectric point 5.48). However, skin care cosmetics are generally slightly acidic (pH 4-6.5). Amino acids with an isoelectric point higher than 7 are prone to protonation of the amino group (-NH2) of the amino acid side chain (forming -NH3 +), which imparts a positive charge and can over-bind with negatively charged components on the skin surface (such as phospholipids and proteins), disrupting the skin barrier. Furthermore, positively charged amino acids can form precipitation with anionic surfactants, negatively charged functional ingredients (such as dipotassium glycyrrhizate and certain plant extracts), and acidic preservatives (such as sodium benzoate) in the formulation, thereby depleting their penetration-enhancing properties and reducing product effectiveness. Therefore, when designing the transdermal absorption carrier composition, the present invention first excluded lysine, arginine, and histidine, which have isoelectric points above 7. From the remaining amino acids, two hydrophilic amino acids and one lipophilic amino acid with isoelectric points below 7 were selected. As shown in Table 3, the results of the human patch test showed that no adverse skin reactions occurred in 30 subjects. Therefore, this transdermal absorption carrier has a good safety profile and does not adversely affect the skin.

[0042] In order to demonstrate the coordination effect of the components in the formula of the present invention, the present invention has made relevant examples and comparative examples, as shown in Table 4 (the parts that are the same as Example 1 are not filled in): Table 4

[0043] The results of the comparative experiment on transdermal efficiency are shown in Table 4. As can be seen from Table 4, the experiment shows that the Ganoderma lucidum extract rich in Ganoderma lucidum peptides, when combined with glycine, cysteine and phenylalanine to form a permeation carrier, has a better effect than the combination with other amino acids. This is because: 1. Molecular size and structure complementarity Glycine: Ganoderma lucidum peptides have the simplest structure, with a single hydrogen atom in the side chain, resulting in a compact molecule. Ganoderma lucidum peptides typically have a specific spatial structure and size. Glycine, with its small size, can fill the gaps in the structure of Ganoderma lucidum peptides, making the entire penetration-enhancing carrier structure more compact and stable. Furthermore, the small size of glycine allows it to easily penetrate the tiny gaps in biological membranes, helping to carry Ganoderma lucidum peptides and other active ingredients across the membrane and promote penetration.

[0044] Cysteine: It contains a unique sulfhydryl group (-SH) and a moderate molecular size. Sulfhydryl groups are highly reactive and can interact with certain groups within Ganoderma lucidum polypeptide molecules (such as disulfide bonds and hydroxyl groups), stabilizing the polypeptide's structure through the formation of new chemical bonds (such as disulfide exchange reactions) or intermolecular forces. Furthermore, the moderate molecular size of cysteine maintains a certain degree of hydrophilicity while also possessing a certain degree of lipophilicity, allowing it to adapt to diverse biomembrane environments. When crossing biomembranes, it synergizes with Ganoderma lucidum polypeptides to enhance their penetration-enhancing effect.

[0045] Phenylalanine: Phenylalanine has a relatively hydrophobic benzene ring side chain and is relatively large. The hydrophobicity of the benzene ring may interact with certain regions of the Ganoderma lucidum polypeptide, helping to adjust the spatial conformation of the Ganoderma lucidum polypeptide, making it more conducive to interaction with biological membranes. Furthermore, the larger benzene ring structure of phenylalanine increases the contact area between the entire permeation-enhancing carrier and the biological membrane. Due to its lipophilicity, it can more easily dissolve and diffuse through the lipid regions of the biological membrane, creating permeation channels for other components.

[0046] 2. Synergistic physical and chemical properties Balance of hydrophilicity and lipophilicity: Glycine and cysteine possess a certain degree of hydrophilicity, while phenylalanine is lipophilic. This combination gives the penetration-enhancing carrier both hydrophilic and lipophilic properties, enabling it to better adapt to the bilayer lipid structure of biological membranes. In aqueous environments, the hydrophilic portion facilitates the dispersion and dissolution of the carrier, facilitating contact with the cell surface. When crossing the biological membrane, the lipophilic phenylalanine portion interacts with the lipid membrane, promoting the entry of the carrier and its active ingredient into the cell, achieving efficient penetration.

[0047] 3. Characteristics of interaction with biofilms Specific binding site: The sulfhydryl group of cysteine can interact with certain components of biological membranes (such as disulfide bonds in proteins), altering the conformation of membrane proteins and increasing membrane permeability. The benzene ring of phenylalanine can bind to certain hydrophobic regions of the membrane through hydrophobic interactions, further stabilizing the binding of the carrier to the membrane. After binding to these two amino acids, Ganoderma lucidum peptides leverage their specific interactions with biological membranes to more effectively guide the carrier and its cargo into cells. In contrast, other amino acids may lack this specific binding ability to biological membranes, resulting in less effective penetration enhancement.

[0048] Regulating membrane fluidity: Phenylalanine, with its large benzene ring structure, can modulate membrane fluidity to a certain extent when inserted into the lipid bilayer of biological membranes. Moderately increasing membrane fluidity facilitates the diffusion of permeation-enhancing agents and their components within the membrane. Cysteine, through its interaction with membrane proteins, may also indirectly influence membrane fluidity and permeability. Combining Ganoderma lucidum peptides with these can better leverage this regulatory effect on membrane fluidity and permeability, achieving enhanced permeation-enhancing effects. Other amino acid combinations may be less effective in modulating membrane properties.

[0049] The above-described embodiments merely represent specific implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of protection of the present application. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the technical concept of the present application, and all such variations and improvements fall within the scope of protection of the present application.

Claims

1. A transdermal absorption carrier, characterized in that: In terms of mass percentage, it is composed of the following components: Ganoderma lucidum extract: 2-5%; Glycine: 0.1-1%; Cysteine: 0.1-1%; Phenylalanine: 0.1-1%; Polyols: 10-40%; The balance was deionized water.

2. A transdermal absorption carrier according to claim 1, characterized in that: The Ganoderma lucidum extract is derived from Ganoderma lucidum.

3. A transdermal absorption carrier according to claim 2, characterized in that: The content of Ganoderma lucidum polypeptide with a molecular weight of 500-800Da in Ganoderma lucidum extract is 0.4%-1.5%.

4. A method for preparing a transdermal absorption carrier, characterized in that: The following steps are involved: S1: Prepare the raw materials according to any one of claims 1 to 3 according to the ratio; S2: Add the polyol to the solvent and stir until completely dissolved; S3: Add glycine, cysteine, and phenylalanine to the solution obtained in S2 in sequence, and stir until the amino acids are completely dissolved; S4: Add the Ganoderma lucidum extract to the solution obtained in S3, and stir until the mixture is uniform to obtain a transdermal absorption carrier.

5. The method for preparing a transdermal absorption carrier according to claim 4, wherein: In S4, the pH value is adjusted to 4-7 after stirring evenly.

6. The method for preparing a transdermal absorption carrier according to claim 4, wherein: The preparation method of Ganoderma lucidum extract comprises the following steps: S101: Grinding the Ganoderma lucidum to obtain Ganoderma lucidum powder; S102: mixing the Ganoderma lucidum powder with a solvent to obtain a Ganoderma lucidum powder liquid; S103: raising the temperature of the Ganoderma lucidum powder liquid to 40° C. to 60° C. for extraction; S104: filtering and concentrating the extracted liquid; S105: aging the obtained concentrated solution at a temperature of 4° C.; S106: removing impurities from the aged concentrated solution, adding polyol, and mixing to obtain the Ganoderma lucidum extract.

7. Use of the transdermal absorption carrier according to any one of claims 1 to 3 as a raw material for cosmetic production.

8. Use of the transdermal absorption carrier according to claim 7 as a raw material for cosmetic production, characterized in that: Cosmetics include serums, lotions, creams, masks, and gels.

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