CTP transdermal repair peptide fusion process

Abstract

The invention discloses a CTP transdermal repair peptide fusion process, and particularly relates to the technical field of biological medicine, and the CTP transdermal repair peptide fusion process comprises the following steps: S1, targeted compound preparation, S2, nano fusion, and S3, transdermal enhancement. By combining the CTP transdermal repair peptide with a nanotechnology, the transdermal absorption efficiency and targeting property of drug molecules are remarkably improved, and repair and regeneration of skin cells are effectively promoted, so that faster, safer and more efficient skin treatment and nursing effects are realized.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and more specifically to a CTP transdermal repair peptide fusion process. Background Art

[0002] In the field of skin repair and care, traditional drugs and skin care products often face problems such as low transdermal absorption efficiency, poor targeting, and low bioavailability, resulting in poor treatment effects and easy side effects. At present, with the advancement of science and technology, especially the rapid development of nanotechnology and biotechnology, new solutions have been provided for skin repair and care.

[0003] In recent years, transdermal drug delivery systems have attracted much attention due to their unique advantages. Transdermal drug delivery systems can directly deliver drugs or active ingredients into the body through the skin, avoiding the inconvenience and side effects of oral or injection administration. However, due to the existence of the skin barrier, many large molecule drugs and active ingredients are difficult to effectively penetrate the skin, limiting the application of transdermal drug delivery systems.

[0004] In order to overcome this problem, researchers began to explore the use of nanotechnology to optimize the transmission and release of drug molecules. Nanotechnology can significantly improve the solubility and stability of drugs, enhance the transdermal absorption of drugs, and achieve targeted drug delivery by preparing nanoparticles, nanofibers and other nanomaterials. At the same time, collagen tripeptide (CTP), as a small molecule peptide, has shown great potential in the field of skin repair and care due to its excellent biological activity and absorbability. CTP can activate the human body to produce new collagen and hyaluronic acid, promote the proliferation and differentiation of skin cells, and thus improve skin quality.

[0005] Based on the above situation, the present invention proposes a CTP transdermal repair peptide fusion process, which aims to achieve more efficient and safer skin repair and care by combining the repair function of CTP and the transdermal advantages of nanotechnology. Summary of the invention

[0006] In order to overcome the above defects of the prior art, the present invention provides a CTP transdermal repair peptide fusion process to solve the problems raised in the above background technology.

[0007] To achieve the above object, the present invention provides the following technical solution: CTP transdermal repair peptide fusion process, comprising the following steps:

[0008] S1. Preparation of targeted complexes: using bioinformatics technology, design and synthesize molecular recognition elements that can bind to specific skin cell surface receptors, and connect the molecular recognition elements to CTP transdermal repair peptides through degradable linkers to form intelligent targeted complexes;

[0009] S2, nanofusion, select nanomaterials with good biocompatibility as carriers, encapsulate the smart targeting complex inside the nanocarrier, and modify the surface of the nanocarrier to enhance its stability and targeting;

[0010] S3. Transdermal enhancement: Transdermal peptides are combined with nanocarriers to utilize their unique penetrating ability to help nanocarriers cross the skin barrier and achieve efficient transdermal penetration. At the same time, combined with microneedle-assisted technology, tiny channels are formed on the skin surface to further promote the transdermal absorption of nanocarriers.

[0011] Preferably, in step S1, the molecular recognition element is a peptide, antibody fragment or derivative thereof screened and designed by bioinformatics, which can specifically recognize and bind to receptors on the surface of target skin cells;

[0012] Among them, the peptide segments include Arg-Gly-Asp and Arginine-Glycine-Aspartic Acid;

[0013] Antibody fragments include Fab fragments and F(ab')2 fragments;

[0014] The derivative is a polyethylene glycol molecule connected to a peptide segment, which can increase the hydrophilicity and stability of the peptide segment, reduce its immunogenicity, and prolong its circulation time in the body. Preferably, a peptide segment is used.

[0015] Preferably, in step S1, the degradable linker is a chemical bond or connection structure that can be broken under specific conditions, and is used to control the release of the drug at the target location, wherein the specific conditions are temperature, pH value changes and light;

[0016] The degradable linker is specifically a glycine-serine peptide bond, which can be broken by the action of proteases in vivo, and the breaking conditions are a temperature of 35° C.-39° C. and a pH value between 5.0-7.4.

[0017] Preferably, in step S1, the purity of the smart targeting complex is not less than 95%, and is prepared by solid phase peptide synthesis.

[0018] Preferably, in step S2, the nanomaterial includes but is not limited to liposomes, polymer nanoparticles, inorganic nanoparticles or a combination of any two thereof, which encapsulate the smart targeting complex by self-assembly or layer-by-layer assembly technology, preferably, liposomes are used;

[0019] Among them, the particle size of liposomes is 50nm-200nm;

[0020] The particle size of polymer nanoparticles is 100nm-300nm;

[0021] The particle size of inorganic nanoparticles is 10nm-200nm.

[0022] Preferably, in step S2, the surface modification of the nanocarrier includes PEGylation and targeting ligand coupling to reduce nonspecific adsorption, prolong in vivo circulation time and enhance targeting, wherein the molecular weight of PEGylated PEG is 2000Da, and the coupling ratio of PEG to the nanocarrier is 1:10 molar ratio. Preferably, PEGylation is used.

[0023] Preferably, in step S3, the transdermal peptide is a short peptide with the ability to efficiently penetrate the skin barrier, which can significantly improve the transdermal efficiency of the drug after combining with the nanocarrier, and its sequence is acssspskhcg.

[0024] Preferably, in step S3, the microneedle-assisted technology includes using a microneedle array made of degradable biomaterial to form tiny channels on the skin surface to promote the transdermal absorption of nanocarriers, the needle tip length of the microneedle array is 500μm-1000μm, the needle tip spacing is 200μm-500μm, and the pressure during use is 0.1MPa-0.5MPa.

[0025] Technical effects and advantages of the present invention:

[0026] 1. The CTP transdermal repair peptide nanocomplex of the present invention optimizes the molecular structure through nanotechnology, so that it can better penetrate the skin barrier and significantly improve the transdermal absorption efficiency, which means that the active ingredients of the drug can reach the target skin layer faster, thereby accelerating the manifestation of the therapeutic effect. Compared with traditional transdermal preparations, the complex of the present invention can play a role more efficiently, reduce drug waste, and improve the therapeutic effect;

[0027] 2. The complex of the present invention can specifically target damaged or repaired skin cells and reduce nonspecific binding on non-target cells. This enhanced targeting not only improves the bioavailability of the drug, but also reduces potential side effects on surrounding healthy tissues, ensuring that patients can obtain better treatment effects in a shorter time while reducing the risk of adverse reactions;

[0028] 3. The CTP transdermal repair peptide nanocomplex of the present invention is rich in highly active repair peptides, which can penetrate deep into the skin to promote cell proliferation, differentiation and migration, thereby accelerating the repair process of skin damage. In addition, the complex can also regulate the skin immune microenvironment, reduce inflammatory response, and create a more favorable environment for skin repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 It is a flow chart of the present invention. DETAILED DESCRIPTION

[0030] Example 1: Targeted repair of specific skin inflammation

[0031] S1. Use bioinformatics technology to screen out peptides (such as Arg-Gly-Asp) that can specifically recognize the target skin cell surface receptors, and connect them with CTP transdermal repair peptides through glycine-serine peptide bonds (breakable at 35℃-39℃, pH5.0-7.4) to form an intelligent targeting complex;

[0032] The purpose of this step is to prepare an intelligent targeting complex that can specifically recognize and bind to the target skin cell surface receptors. The Arg-Gly-Asp (RGD) peptide segment is a common cell adhesion peptide that can specifically recognize and bind to integrin receptors on the surface of various cells, while the glycine-serine peptide bond (Gly-Ser) can be broken under specific conditions (such as body temperature and a specific pH range) to release the CTP transdermal repair peptide.

[0033] S2, liposomes were selected as nanocarriers, the smart targeting complex was encapsulated inside by self-assembly technology, and the surface of liposomes was PEGylated (PEG molecular weight was 2000Da, and the coupling ratio of PEG to liposomes was 1:10 molar ratio) to enhance its stability and targeting;

[0034] The purpose of this step is to encapsulate the smart targeting complex inside the nanocarrier to enhance its stability and targeting. Liposomes, a nanoparticle composed of a phospholipid bilayer membrane, can encapsulate and protect the drug molecules inside. Polyethylene glycol (PEG) molecules are used to modify the liposome surface to reduce nonspecific adsorption and prolong the circulation time in the body.

[0035] S3, combining a transdermal peptide (sequence: acssspskhcg) with the ability to efficiently penetrate the skin barrier with liposomes, and combining it with microneedle-assisted technology (microneedle array tip length: 800 μm, tip spacing: 300 μm, use pressure: 0.3 MPa) to form tiny channels on the skin surface of the inflamed area to promote the transdermal absorption of liposomes;

[0036] This step uses transdermal peptides and microneedle-assisted technology to improve the transdermal efficiency of nanocarriers. Transdermal peptides are short peptides with the ability to efficiently penetrate the skin barrier. Their sequence is acssspskhcg, which can destroy the lipid bilayer structure of the skin barrier and promote the penetration of nanocarriers. The microneedle array made of degradable biomaterials forms tiny channels on the skin surface, further promoting the transdermal absorption of nanocarriers.

[0037] In summary, this embodiment achieves efficient repair of specific skin inflammation areas through specific recognition and targeted release, reduces the distribution of drugs in non-target areas, and improves the treatment effect.

[0038] Example 2: Transdermal repair for anti-aging

[0039] S1. Using bioinformatics technology, design and synthesize an antibody fragment (such as Fab fragment) that can widely bind to skin cell surface receptors, and connect it to the CTP transdermal repair peptide through a degradable linker (such as a temperature-sensitive linker that breaks near body temperature) to form an intelligent targeting complex;

[0040] This step uses antibody fragments (such as Fab fragments) that widely bind to skin cell surface receptors as molecular recognition elements to achieve a repair effect on a variety of skin cells.

[0041] S2, polymer nanoparticles are selected as nanocarriers, the smart targeting complex is encapsulated by layer-by-layer assembly technology, and the surface of the nanoparticles is modified by PEGylation and targeting ligand coupling to enhance its stability and targeting;

[0042] In this step, polymer nanoparticles are used as carriers, which may have better drug encapsulation efficiency and sustained release effect.

[0043] S3, combining transdermal peptides (sequence: acssspskhcg) with polymer nanoparticles, and combining with microneedle-assisted technology (microneedle array tip length: 500 μm, tip spacing: 200 μm, use pressure: 0.2 MPa), to form tiny channels in the facial skin to promote transdermal absorption of nanoparticles;

[0044] This step utilizes transdermal peptides and microneedle-assisted technology to improve transdermal efficiency.

[0045] In summary, this embodiment achieves comprehensive repair and anti-aging effects on skin cells through extensive cell binding ability and efficient transdermal efficiency, and improves the firmness and glossiness of facial skin.

[0046] Example 3: Personalized transdermal repair solution

[0047] S1. According to the patient's skin type and pathological condition, bioinformatics technology is used to screen and design suitable molecular recognition elements (such as peptides, antibody fragments or their derivatives), and they are connected to CTP transdermal repair peptides through degradable linkers to form personalized intelligent targeting complexes;

[0048] This step screens and designs appropriate molecular recognition elements and CTP transdermal repair peptides according to the patient's skin type and pathological condition.

[0049] S2. According to the specific needs of patients, appropriate nanomaterials (such as liposomes, polymer nanoparticles or inorganic nanoparticles) are selected as carriers, and the smart targeting complex is encapsulated by appropriate assembly technology, and surface modification is performed to enhance its stability and targeting;

[0050] In this step, the most suitable nanomaterial for the patient is selected as the carrier and the corresponding surface modification is performed.

[0051] S3. According to the patient's skin barrier characteristics and treatment needs, select appropriate transdermal peptides and microneedle-assisted technical parameters (such as transdermal peptide sequence, needle tip length and spacing of the microneedle array, application pressure, etc.) to achieve the best transdermal absorption effect;

[0052] This step selects appropriate transdermal peptide and microneedle-assisted technology parameters based on the patient's skin barrier properties and treatment needs.

[0053] In summary, this embodiment meets the treatment needs of different patients through a personalized customized process solution, and improves the pertinence and effectiveness of the treatment.

[0054] The fusion process of the present invention is subjected to data testing, and the test results are shown in the following table:

[0055] Test method:

[0056] 1. Transdermal absorption efficiency test: a certain number of healthy volunteers were selected and randomly divided into two groups. The complex of the present invention and the existing product were used respectively. Within a specified time (such as 24 hours), the residual amount of CTP transdermal repair peptide labeled with isotope or fluorescence was measured in each layer of the skin (such as epidermis and dermis) through skin absorption experiment, and the transdermal absorption rate was calculated, that is, the percentage of the residual amount of CTP transdermal repair peptide in each layer of the skin to the total amount used;

[0057] 2. Targeting test: use the complex of the present invention labeled with fluorescent dye to incubate on the target skin cells cultured in vitro, observe and count the number of fluorescently labeled cells under a fluorescence microscope, and calculate the targeting efficiency. At the same time, set up a control group and use unlabeled complexes or existing products to perform the same experiment to eliminate the influence of nonspecific binding;

[0058] 3. Evaluation of the repair effect: establish an animal model of skin inflammation or damage (such as a mouse model), and randomly divide the model into three groups: a treatment group (using the complex of the present invention), a positive control group (using a known effective repair product), and a negative control group (not using any treatment). During the prescribed treatment cycle (such as 7 days, 14 days), regularly observe and record the improvement of skin inflammation or damage, and use methods such as histological scoring and inflammatory factor level detection to quantify the repair effect.

[0059] Data table:

[0060]

[0061] The data collected by the above test method show that the complex of the present invention is significantly superior to existing products in terms of transdermal absorption efficiency, targeting and repair effect. These results prove that the present invention has good effects compared with the existing technology and has potential clinical application value and market prospects.

[0062] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. CTP transdermal repair peptide fusion process, characterized by: The following steps are involved: S1. Preparation of targeted complexes: using bioinformatics technology, design and synthesize molecular recognition elements that can bind to specific skin cell surface receptors, and connect the molecular recognition elements to CTP transdermal repair peptides through degradable linkers to form intelligent targeted complexes; S2, nanofusion, select nanomaterials with good biocompatibility as carriers, encapsulate the smart targeting complex inside the nanocarrier, and modify the surface of the nanocarrier to enhance its stability and targeting; S3. Transdermal enhancement: Transdermal peptides are combined with nanocarriers to utilize their unique penetrating ability to help nanocarriers cross the skin barrier and achieve efficient transdermal penetration. At the same time, combined with microneedle-assisted technology, tiny channels are formed on the skin surface to further promote the transdermal absorption of nanocarriers.

2. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S1, the molecular recognition element is a peptide, antibody fragment or its derivatives screened and designed by bioinformatics, which can specifically recognize and bind to receptors on the surface of target skin cells; Among them, the peptide segments include Arg-Gly-Asp and Arginine-Glycine-Aspartic Acid; Antibody fragments include Fab fragments and F(ab')2 fragments; Derivatives are polyethylene glycol molecules connected to peptides, which can increase the hydrophilicity and stability of the peptides, reduce their immunogenicity, and prolong their circulation time in the body.

3. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S1, the degradable linker is a chemical bond or connection structure that can be broken under specific conditions, and is used to control the release of the drug at the target location, wherein the specific conditions are temperature, pH value changes and light; The degradable linker is specifically a glycine-serine peptide bond, which can be broken by the action of proteases in vivo, and the breaking conditions are a temperature of 35° C.-39° C. and a pH value between 5.0-7.

4.

4. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S1, the purity of the smart targeting complex is not less than 95%, and is prepared by solid phase peptide synthesis.

5. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S2, the nanomaterials include but are not limited to liposomes, polymer nanoparticles, inorganic nanoparticles or a combination of any two thereof, which encapsulate the smart targeting complex by self-assembly or layer-by-layer assembly technology; Among them, the particle size of liposomes is 50nm-200nm; The particle size of polymer nanoparticles is 100nm-300nm; The particle size of inorganic nanoparticles is 10nm-200nm.

6. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S2, the surface modification of the nanocarrier includes PEGylation and targeting ligand coupling to reduce nonspecific adsorption, prolong the in vivo circulation time and enhance targeting, wherein the molecular weight of PEGylated PEG is 2000Da, and the coupling ratio of PEG to the nanocarrier is 1:10 molar ratio.

7. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S3, the transdermal peptide is a short peptide with the ability to efficiently penetrate the skin barrier. After combining with the nanocarrier, it can significantly improve the transdermal efficiency of the drug. Its sequence is acssspskhcg.

8. The CTP transdermal repair peptide fusion process according to claim 1, characterized in that: In step S3, the microneedle-assisted technology includes using a microneedle array made of degradable biomaterial to form tiny channels on the skin surface to promote the transdermal absorption of nanocarriers. The needle tip length of the microneedle array is 500μm-1000μm, the needle tip spacing is 200μm-500μm, and the pressure during use is 0.1MPa-0.5MPa.

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