Transdermal tripeptide and application thereof
By designing and synthesizing transdermal tripeptides with the amino acid sequence Ser-Cys-Arg, the problem of insufficient existing permeability technology is solved, good transdermal effect and biocompatibility are achieved, and it is suitable for the preparation of a variety of transdermal products.
Patent Information
- Application Number
- CN202311070922.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-08-23
- Publication Date
- 2025-02-25
AI Technical Summary
Existing penetration-promoting technologies include the difficulty in synthesis of drug-vector prodrugs, limited effect of ion pairing, cumbersome process of vesicle method, microneedle method will leave injuries, chemical penetration promoters destroy skin structure, and physical penetration-promoting methods require special instruments, etc., which are difficult to effectively promote macromolecular transdermality.
A new transdermal tripeptide is designed and synthesized, with an amino acid sequence of Ser-Cys-Arg, which has good permeability and biocompatibility, and is used to prepare transdermal products such as beauty preparations, hairdressing preparations and pharmaceutical compositions.
This transdermal tripeptide has obvious transdermal ability. Although its permeability effect is lower than acetyl hexapeptide-1, it is better than menthol. It has a simple structure, small molecular weight, high biocompatibility, and has no toxic effect on cells. It is suitable for the preparation of permeability products.
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Figure CN119504927A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a transdermal tripeptide and application thereof, belonging to the technical field of active polypeptides. Background Art
[0002] The skin is the largest organ. Whether it is transdermal drug delivery for the treatment of skin diseases or for the purpose of beauty and skin care, how to promote the transdermal absorption of active ingredients is the focus of research by scientific researchers.
[0003] Existing penetration-enhancing technologies include drug-media interactive drug delivery, ion pairing, vesicle method, microneedle, chemical penetration enhancer, physical method (laser introduction, ultrasound introduction, electroporation), etc., but these technologies have many shortcomings, such as drug-media prodrugs are difficult to synthesize, ion pairing method only works on a part of ionized drugs, the synthesis process of vesicle method is cumbersome, microneedle method will leave certain wounds, chemical penetration enhancer will destroy the normal structure of the skin, physical penetration method process is cumbersome and must rely on special instruments, etc. Biological penetration-enhancing technology uses a class of polypeptide molecules with skin penetration ability, about 10 to 30 amino acids, which can effectively promote the permeation of macromolecules. Transdermal peptides are non-irritating, will not cause skin allergies and damage, have good compatibility between drugs and materials, have stable physical and chemical properties, fast onset time, and long action time.
[0004] Transdermal peptides are polypeptides with enhanced transdermal function, which can enhance and / or facilitate the penetration of active molecules through the skin, thereby increasing the dose of active molecules entering the systemic circulation or increasing the dose of active molecules reaching target organs, tissues and cells, and can be used for transdermal administration of large molecular weight drugs such as polypeptides, proteins and nucleic acid molecules.
[0005] Acetyl hexapeptide-1 (Ac-Nle-Ala-His-D-Phe-Arg-Trp-NH2) can induce the release of interleukins, and the release of interleukins increases the permeability of capillaries. Therefore, acetyl hexapeptide-1 has a certain permeability-promoting effect.
[0006] Menthol, as a widely recognized percutaneous penetration enhancer, can destroy the lamellar structure of the stratum corneum and induce lipid cells to form a single-layer vacuolar structure, but it can cause functional damage to the stratum corneum and cause toxicity to the skin. Wan et al. used osthole as a target drug to conduct an in vitro percutaneous penetration experiment. When the dosage of menthol was as high as 0.5%, the permeation enhancement ratio was only 5.19.
[0007] Chinese patent document CN106084006A provides a polypeptide with transdermal function or transdermal enhancement function and a nucleic acid sequence encoding the polypeptide. The amino acid sequence of the polypeptide is ACSSTKKHCG, which can promote and / or enhance the transdermal penetration of other substances, including small molecule active substances, large molecule active substances such as proteins, nucleic acids, etc.
[0008] It can be seen that the prior art has proposed a technical solution that a polypeptide composed of about 10-30 amino acids can enhance the transdermal effect, and the chain length of the short transdermal peptide is relatively short, generally within 30 amino acids, and the synthesis process is relatively simpler. In addition, the short transdermal peptide can assist macromolecular substances to pass through the cell membrane without any receptors and will not damage the biological membrane. However, through the prior art and the inventor's previous research, it was found that when the amino acid sequence changes, including the number and order of amino acids, its transdermal effect will also change significantly, lacking predictability. In order to enrich the product variety, different transdermal peptides can be further explored. Summary of the invention
[0009] In view of the shortcomings of the prior art, the present invention provides a transdermal tripeptide and its application. The present invention designs and synthesizes a new transdermal tripeptide, which has good penetration-promoting effect and biocompatibility.
[0010] The technical solution of the present invention is as follows:
[0011] A transdermal tripeptide, the amino acid sequence of which is: Ser-Cys-Arg, or Ser-Met-Arg, or Ser-Cys-Lys, in order from C-terminus to N-terminus.
[0012] Preferably according to the present invention, the amino acid sequence of the transdermal tripeptide is: Ser-Cys-Arg.
[0013] Application of the above transdermal tripeptide in the preparation of transdermal products.
[0014] Preferably according to the present invention, the transdermal products include cosmetic preparations, hair preparations, medicines, and foods; further preferably, the cosmetic preparations include skin care products and cosmetics.
[0015] A cosmetic preparation comprising the above transdermal tripeptide and at least one active ingredient for skin care, skin function improvement or skin color regulation.
[0016] A hairdressing preparation comprises the above transdermal tripeptide and at least one hairdressing active ingredient, wherein the hairdressing active ingredient comprises an ingredient having the effects of promoting hair growth, preventing hair loss, and changing hair structure, composition or color.
[0017] A pharmaceutical composition comprises the transdermal tripeptide and at least one active pharmaceutical ingredient in an effective dose for treating a disease.
[0018] A method for assisting the transdermal penetration of active substances is to mix the above transdermal tripeptide with an effective dose of active substances and apply the mixture to the skin surface.
[0019] Beneficial effects:
[0020] The present invention designs and synthesizes a new transdermal tripeptide Ser-Cys-Arg, which has obvious transdermal ability. Although its penetration-promoting effect is lower than that of acetyl hexapeptide-1, it is still better than menthol. It has a simple structure, a small molecular weight, high biocompatibility, and no toxicity to cells. It can be used for the preparation of penetration-promoting products and has broad development prospects and application potential. At the same time, the present invention also synthesizes transdermal tripeptides Ser-Met-Arg and Ser-Cys-Lys, whose transdermal delivery effect is slightly lower than that of Ser-Cys-Arg, but still has obvious penetration-promoting effect. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 Schematic diagram of the synthetic route of the transdermal tripeptide Ser-Cys-Arg; in the figure, Aa represents amino acid.
[0022] Figure 2 This is the infrared spectrum of the transdermal tripeptide Ser-Cys-Arg.
[0023] Figure 3 This is the mass spectrum of the transdermal tripeptide Ser-Cys-Arg.
[0024] Figure 4 Schematic diagram of the Franz diffusion cell.
[0025] Figure 5 This is the cumulative permeation curve of diclofenac sodium per unit area in different treatment groups.
[0026] Figure 6 It is a bar graph of the cell viability of human skin fibroblasts under different concentrations of transdermal tripeptides.
[0027] Figure 7 This is the cumulative permeation curve of diclofenac sodium per unit area in different transdermal tripeptide treatment groups. DETAILED DESCRIPTION
[0028] The technical scheme of the present invention is further described below in conjunction with the examples, but the protection scope of the present invention is not limited thereto. The drugs and reagents involved in the examples, unless otherwise specified, are all common commercially available products; the experimental steps involved in the examples, unless otherwise specified, are all conventional technical operations in the art.
[0029] Example 1: Preparation of transdermal tripeptides
[0030] The synthetic route of the transdermal tripeptide Ser-Cys-Arg is as follows Figure 1 As shown, the specific steps are as follows:
[0031] (1) Weigh 3 g of RINK resin (substitution degree 0.3 mmol / g) into a 150 mL reactor and soak it with 50 mL of dichloromethane (DCM) (the C-terminus is the carboxyl end);
[0032] (2) After 2 hours, wash the resin with 3 times the volume of N,N-dimethylformamide (DMF) and then drain it. Repeat this process four times and drain the resin for later use.
[0033] (3) Add 8 mL of 20% piperidine (piperidine / DMF = 1:4, volume ratio) to the reactor and shake on a decolorizing shaker for 20 min to remove the Fmoc protecting group on the resin. After removing the protecting group, wash four times with DMF 3 times the volume of the resin and then drain;
[0034] (4) Take a small amount of resin and test it using the ninhydrin (hydrated ninhydrin) method. If the resin has color, it means that the deprotection is successful.
[0035] (5) Weigh 1.5 g of amino acid Ser into a 50 mL centrifuge tube, add 5 mL of DMF to dissolve it, and then add it to the above reactor;
[0036] (6) Take 5 mL of 1-hydroxy-benzotriazole (HOBT, condensing agent) in a 50 mL centrifuge tube, add 20 mL of DMF to dissolve it, then add 3 mL of N,N-diisopropylcarbodiimide (DIC, polypeptide condensing agent), shake well for 1 min, add the solution to the above reactor after it becomes clear, and then place the reactor in a shaker at 30 °C for reaction;
[0037] (7) After 2 hours, the mixture was capped with 10 mL of acetic anhydride (acetic anhydride: DIEA (condensing agent): DCM = 1:1:2, volume ratio) for half an hour, then washed four times with 3 times the volume of the resin in DMF, and dried for later use;
[0038] (8) Add 8 mL of 20% piperidine (piperidine / DMF = 1:4, volume ratio) to the reactor and shake on a decolorizing shaker for 20 min to remove the Fmoc protecting group on the resin. After the protecting group is removed, wash four times with DMF 3 times the volume of the resin and then drain;
[0039] (9) Take a small amount of resin and test it using the ninhydrin (hydrated ninhydrin) method. If the resin has color, it means that the deprotection is successful;
[0040] (10) Weigh 1.5 g of amino acid Cys into a 50 mL centrifuge tube, add 5 mL of DMF to dissolve it, and then add it to the above reactor;
[0041] (11) Take 5 mL of 1-hydroxy-benzotriazole (HOBT, condensing agent) in a 50 mL centrifuge tube, add 20 mL of DMF to dissolve it, then add 3 mL of N,N-diisopropylcarbodiimide (DIC, polypeptide condensing agent), shake well for 1 min, add the solution to the above reactor after it becomes clear, and then place the reactor in a shaker at 30 °C for reaction;
[0042] (12) After 2 hours, the mixture was capped with 10 mL of acetic anhydride (acetic anhydride: DIEA (condensing agent): DCM = 1:1:2, volume ratio) for half an hour, then washed four times with 3 times the volume of the resin in DMF, and dried for later use;
[0043] (13) 8 mL of 20% piperidine (piperidine / DMF = 1:4, volume ratio) was added to the reactor and the resin was shaken on a decolorization shaker for 20 min to remove the Fmoc protecting group on the resin. After the protecting group was removed, the resin was washed four times with DMF 3 times the volume of the resin and then dried;
[0044] (14) Take a small amount of resin and test it using the ninhydrin (hydrated ninhydrin) method. If the resin has color, it means that the deprotection is successful.
[0045] (15) Weigh 1.5 g of amino acid Arg into a 50 mL centrifuge tube, add 5 mL of DMF to dissolve it, and then add it to the above reactor;
[0046] (16) Take 5 mL of 1-hydroxy-benzotriazole (HOBT, condensing agent) in a 50 mL centrifuge tube, add 20 mL of DMF to dissolve it, then add 3 mL of N,N-diisopropylcarbodiimide (DIC, polypeptide condensing agent), shake well for 1 min, add the clarified solution to the above reactor, and then place the reactor in a shaker at 30 °C for reaction;
[0047] (17) After 2 hours, the mixture was capped with 10 mL of acetic anhydride (acetic anhydride: DIEA (condensing agent): DCM = 1:1:2, volume ratio) for half an hour, then washed four times with 3 times the volume of the resin in DMF and dried for later use;
[0048] (18) 8 mL of 20% piperidine (piperidine / DMF = 1:4, volume ratio) was added to the reactor and the resin was shaken on a decolorization shaker for 20 min to remove the Fmoc protecting group on the resin. After the protecting group was removed, the resin was washed four times with DMF 3 times the volume of the resin and then dried;
[0049] (19) Take a small amount of resin and test it using the ninhydrin (hydrated ninhydrin) method. If the resin has color, it means that the deprotection is successful.
[0050] (20) The peptide was cleaved from the resin using 95% cleavage solution (trifluoroacetic acid: 1,2-ethanedithiol: triisopropylsilane: water = 95:2:2:1, volume ratio) (10 mL of cleavage solution per gram of resin) and centrifuged four times with icy ether (cleavage solution: ether = 1:9, volume ratio); finally, it was separated and purified by HPLC and then freeze-dried to obtain the transdermal tripeptide Ser-Cys-Arg.
[0051] The infrared spectrum of the above-obtained transdermal tripeptide Ser-Cys-Arg is as follows: Figure 2 As shown in the figure, the characteristic absorption peak of the transdermal tripeptide Ser-Cys-Arg appears at 3351cm -1 、3075cm -1 、1670cm -1 、1541cm -1 、1431cm -1 、1202cm -1 、1136cm -1 、1202cm -1 、1136cm -1 、980cm -1 At , they belong to the stretching vibration of NH bond in -CO=NH- and NH in NH2, the stretching vibration of associating -NH- bond, the amide I band of -CO=NH-, the stretching vibration of -C=N, the deformation vibration absorption peak of -CH3-, the deformation vibration absorption peak of -CH2-, the stretching vibration of -CO-, the stretching vibration of -CN- bond, the stretching vibration of -CS- bond and the bending vibration of -OH in -COOH.
[0052] The mass spectrometry results of the transdermal tripeptide Ser-Cys-Arg obtained above are as follows Figure 3 As shown in the figure, the simulated mass-to-charge ratio of the transdermal tripeptide Ser-Cys-Arg is 364.15, and the measured mass-to-charge ratio of the mass spectrum is 364.36.
[0053] The above results proved that the transdermal tripeptide Ser-Cys-Arg had been successfully synthesized.
[0054] Example 2: Transdermal delivery study of the transdermal tripeptide Ser-Cys-Arg
[0055] The diffusion cell experiment was conducted using mouse skin as the substrate. The specific steps are as follows:
[0056] 1. Preparation of ex vivo mouse skin
[0057] Take healthy mice, anesthetize them with 10% urethane solution (dosage: 8 mL / kg), first shave the coarse hair on the back of the mice, then patiently cut the hair so as not to affect the contact between the drug and the skin, then inject an overdose of urethane solution to kill the mice, cut the back skin, and finally carefully remove the subcutaneous fat and mucous tissue, clean the mouse skin with PBS buffer, spread it flat on aluminum foil, and store it in a -20℃ refrigerator for later use.
[0058] 2. Construction of in vitro percutaneous absorption experimental device
[0059] The Franz diffusion cell used in the experiment is as follows Figure 4 As shown in the figure, the speed of the star-shaped stirrer in the experiment is 500 r / min, the volume of the receiving chamber is 6.5 mL, and the effective diffusion area is 0.785 cm 2 In the experiment, PBS buffer (pH 7.4) was used as the receiving medium and the experiment was carried out in a constant temperature water bath at (32±0.5)℃.
[0060] Before the experiment, first heat the PBS buffer to be used to (32±0.5)℃, and turn on the constant temperature water bath system. Take out the prepared mouse skin, rinse it carefully with PBS buffer, wipe the liquid on the surface of the skin dry and place it on the diffusion cell, with the mouse skin stratum corneum facing up, and discard the receiving solution after balancing for 30 minutes. Add fresh PBS buffer to the receiving chamber again, place the mouse skin on the diffusion cell, drain the bubbles under the skin, and add PBS buffer dissolved with diclofenac sodium to the supply chamber. Take samples of 200μL at the 2nd, 4th, 6th, and 8th hours, and add fresh receiving solution of the same volume and temperature. After filtering the sample through a 0.45μm microporous filter membrane, dilute it to a certain multiple, and determine its concentration using a liquid chromatograph.
[0061] 3. HPLC column preparation
[0062] Chromatographic column: Amethyst C18-H (250mm×4.6mm, 5μm), mobile phase: methanol-0.4% glacial acetic acid solution (80:20), detection wavelength is 254nm, flow rate is 1.0mL / min, column temperature: 30℃, injection volume is 10μL.
[0063] 4. Drug concentration screening
[0064] Take appropriate amount of diclofenac sodium in PBS buffer to prepare 0.1, 0.2, 0.3, 0.4, 0.5, 0.6% (g / mL) diclofenac sodium test solution, and measure its 8h permeability. The results show that when the drug concentration is greater than 0.2%, its 8h permeability stops rising, so the drug concentration of diclofenac sodium solution is specified to be 0.1%.
[0065] 5. In vitro percutaneous penetration test
[0066] This experiment was divided into four groups, namely, transdermal tripeptide group, acetyl hexapeptide-1 group, menthol group, and blank control group. The above-mentioned permeation enhancers were dissolved in PBS buffer containing 0.1% diclofenac sodium, wherein the concentration of transdermal tripeptide was 0.08%, and the concentrations of menthol and acetyl hexapeptide-1 were 0.5%, respectively. First, the PBS buffer to be used was heated to (32±0.5)℃, and the constant temperature water bath system was turned on. Take out the prepared mouse skin, rinse it carefully with PBS buffer, wipe the liquid on the surface of the skin dry and place it on the diffusion cell, with the mouse skin stratum corneum facing up, and discard the receiving solution after balancing for 30 minutes. Add fresh PBS buffer to the receiving chamber again, place the mouse skin on the diffusion cell, drain the bubbles under the skin, and add PBS buffer dissolved with the permeation enhancer to the supply chamber. Take samples of 200μL at 2, 4, 6, and 8h, and supplement with fresh receiving solution of the same volume and temperature. The sample was filtered through a 0.45 μm microporous filter membrane and then diluted to a certain multiple, and the concentration of diclofenac sodium was determined by liquid chromatography.
[0067] Among them, the cumulative permeation amount of diclofenac sodium per unit area (Q n ) is calculated by formula (1):
[0068]
[0069] In formula (1), Q n is the cumulative permeation per unit area at the nth time point (μg / cm 2 ), C n is the drug concentration measured at the nth time point (μg / mL), V is the volume of the receptor chamber (mL), C i is the drug concentration measured at each sampling (μg / mL), V i is the volume of each sampling (mL), A is the effective diffusion area (cm 2 ).
[0070] Steady state flux J s , Permeability coefficient K p , permeability enhancement ratio ER, and permeability are calculated by formulas (2), (3), (4), and (5), respectively:
[0071]
[0072]
[0073]
[0074] Permeability (%) = Q n / Initial drug loading in the supply chamber × 100% (5)
[0075] In the formula, Q p is the total amount of permeated drug (μg), A is the effective diffusion area (cm 2 ), t is the corresponding diffusion time (h), C d is the initial drug loading concentration in the supply chamber (μg / cm 3 ), K Pi is the permeability coefficient of the sample (cm / h), K P0 is the permeability coefficient of the blank control group (cm / h), Q n is the cumulative permeation per unit area at the nth time point (μg / cm 2 ).
[0076] The cumulative permeation amount of diclofenac sodium per unit area in different treatment groups is as follows Figure 5 As shown by Figure 5 It can be seen that after adding various penetration enhancers for 8 hours, the order of the cumulative permeation amount of diclofenac sodium per unit area is: Q 乙酰基六肽-1 >Q 透皮三肽 >Q 薄荷醇 >Q 空白对照组 Although the cumulative permeation amount of diclofenac sodium per unit area of the transdermal tripeptide is lower than that of acetyl hexapeptide-1, it is still significantly higher than menthol, and has a significant transdermal effect.
[0077] The main transdermal permeation parameters of drugs in different treatment groups are shown in Table 1. The data in Table 1 show that the drug permeability of the transdermal tripeptide is second only to acetyl hexapeptide-1.
[0078] Table 1. Main percutaneous permeation parameters of drugs in different treatment groups
[0079] Permeation enhancers <![CDATA[J s (μg / h cm 2 )]]> <![CDATA[K p ×10 -2 (cm / h)]]> ER Permeability Transdermal Tripeptide 28.86 2.89 2.08 9.6% Acetyl Hexapeptide-1 48.93 4.89 3.5 15.3% Menthol 20.59 2.05 1.47 6.4% Blank control group 13.90 1.39 1 4.3%
[0080] According to the research results, the transdermal heptapeptide has a good transdermal delivery rate. Compared with the existing permeation enhancers (acetyl hexapeptide-1, menthol), its transdermal delivery rate is lower than that of acetyl hexapeptide-1, but still higher than that of menthol.
[0081] Example 4: Biocompatibility test
[0082] Cytotoxicity experiments are conducted in vitro to simulate the growth environment of organisms. They can screen out the cytotoxicity of batches of samples in a short period of time and are an important basis for other cell experiments. This experiment uses human skin fibroblasts as a cell model, and the concentrations of the samples to be tested are set at 60μg / mL, 80μg / mL, 100μg / mL, 120μg / mL, and 140μg / mL, and the CCK-8 method is used for determination. The specific steps are as follows:
[0083] (1) Cell Counting Kit-8 (CCK-8) reagent can be used to quickly and conveniently identify the toxicity of analytical substances. The working principle is as follows: it contains WTS-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid benzene)-2H-tetrazolyl monosodium salt], whose molecular structure contains multiple nitro (-NO2) and aromatic sulfonic acid (-SO3H) groups. These groups have strong light absorption and undergo photolysis to produce active substances such as free radicals or ions. These active substances further undergo redox reactions. Under the action of 1-Methoxy PMS, they are easily reduced to yellow formazan substances by dehydrogenases in cells. The amount of the product is proportional to the cell survival rate. The yellow formazan product is characterized by high water solubility and special absorption at 450nm. The cytotoxicity of the sample to be tested can be determined by detecting its absorbance.
[0084] Human skin fibroblasts were cultured to an appropriate density, digested with trypsin, and then prepared into a cell suspension, which was inoculated in a 96-well plate. 100 μL of the cell suspension was inoculated in each well, and the number of cells in each well was 6-8×10 3 The cells were incubated at 37°C, 5% CO2 for 24 h.
[0085] (2) This experiment set up a blank control group and an experimental group. The concentration of the test sample (i.e., transdermal tripeptide) in the experimental group was set at 5 concentration gradients, and at least three replicates were set for each concentration. No reagent was added to the blank control group. After the cells were firmly attached to the wall overnight, the culture medium was discarded, and fresh culture medium containing different amounts of the test sample was added. After the operation was completed, the cells were incubated at 37°C and 5% CO2 for 24 hours.
[0086] (3) Take the 96-well plate out of the incubator, add CCK-8 detection solution at a volume of 10 μL per well, and incubate in an incubator at 37°C and 5% CO2 for 3 h.
[0087] (4) After incubation, take out the sample and measure the absorbance at 450 nm.
[0088] (5) Result analysis: Using the measured absorbance value, the cell viability was calculated according to the following formula:
[0089]
[0090] In the formula, A x represents the absorbance of the experimental group at 450 nm, and A0 represents the absorbance of the blank control group at 450 nm.
[0091] The results are as follows Figure 6 As shown, analysis shows that the cell survival rate of human skin fibroblasts of the transdermal tripeptide exceeds 85%, and it has basically no toxic effect on the cells.
[0092] Embodiment 4:
[0093] In addition to the above-mentioned transdermal tripeptide Ser-Cys-Arg, two other transdermal tripeptides were designed: Ser-Met-Arg and Ser-Cys-Lys.
[0094] The transdermal tripeptides Ser-Met-Arg and Ser-Cys-Lys were synthesized according to the method of Example 1, and their transdermal effects were studied according to the experimental method of Example 2.
[0095] The cumulative permeation amount of diclofenac sodium per unit area in different transdermal tripeptide treatment groups is as follows Figure 7 As shown by Figure 7 It can be seen that after adding different transdermal tripeptides for 8 hours, the order of the cumulative permeation amount of diclofenac sodium per unit area is: Ser-Cys-Arg group > Ser-Met-Arg group > Ser-Cys-Lys. The results show that although the transdermal delivery effect of the transdermal tripeptides Ser-Met-Arg and Ser-Cys-Lys is slightly lower than that of Ser-Cys-Arg, they still have a significant permeation-enhancing effect.
[0096] It is speculated that the reason why the above three transdermal tripeptides have a permeation-promoting effect is that, since all three tripeptides contain quinolineethyl, thiol, and aminoimino groups, it may be that when the tripeptide peptide chain contains a combination of quinolineethyl, thiol, and aminoimino, the tripeptide has a certain permeation-promoting effect.
[0097] According to the method of Example 3, it was verified that the above two transdermal tripeptides Ser-Met-Arg and Ser-Cys-Lys also have basically no toxic effect on cells.
Claims
1. A transdermal tripeptide, characterized in that: Its amino acid sequence is: Ser-Cys-Arg, or Ser-Met-Arg, or Ser-Cys-Lys, in order from C-terminus to N-terminus.
2. The transdermal tripeptide according to claim 1, characterized in that Its amino acid sequence is: Ser-Cys-Arg.
3. Use of the transdermal tripeptide according to claim 1 or 2 in the preparation of transdermal products.
4. The use according to claim 3, characterized in that The transdermal products include cosmetic preparations, hairdressing preparations, medicines, and foods.
5. The use according to claim 4, characterized in that The cosmetic preparations include skin care products and cosmetics.
6. A cosmetic preparation, characterized in that The invention comprises the transdermal tripeptide according to claim 1 or 2, and at least one active ingredient for skin care, skin function improvement or skin color regulation.
7. A hairdressing preparation, characterized in that: The invention comprises the transdermal tripeptide according to claim 1 or 2, and at least one hair-beautifying active ingredient, wherein the hair-beautifying active ingredient comprises an ingredient having the effects of promoting hair growth, preventing hair loss, and changing hair structure, composition or color.
8. A pharmaceutical composition, characterized in that The invention comprises the transdermal tripeptide according to claim 1 or 2, and at least one active pharmaceutical ingredient in an effective dose for treating a disease.
9. A method for assisting the transdermal delivery of an active substance, characterized in that: The transdermal tripeptide according to claim 1 or 2 is mixed with an effective dose of active substance and applied to the skin surface.
Citation Information
Patent Citations
Transdermal peptide and application thereof
CN106084006A
Cited By
Oligopeptide dimer and nanocomposite thereof
CN122103248A
A short peptide dimer and its nanocomplex
CN122103248B