CN113694175A - Sophora flavescens base ionic liquid conotoxin polypeptide solution, preparation method and application thereof - Google Patents
Sophora flavescens base ionic liquid conotoxin polypeptide solution, preparation method and application thereof Download PDFInfo
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- CN113694175A CN113694175A CN202110921501.3A CN202110921501A CN113694175A CN 113694175 A CN113694175 A CN 113694175A CN 202110921501 A CN202110921501 A CN 202110921501A CN 113694175 A CN113694175 A CN 113694175A
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- preparation
- conotoxin polypeptide
- ionic liquid
- matrine
- solution
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Abstract
The invention discloses a lightyellow sophora root base ionic liquid conotoxin polypeptide solution, a preparation method and application thereof, wherein the preparation method comprises the following steps: providing a conotoxin polypeptide mother liquor; adding matrine and organic acid into water to obtain matrine organic acid ion salt solution; and mixing the matrine organic acid ionic salt solution and the conotoxin polypeptide mother solution to obtain a matrine ionic liquid conotoxin polypeptide solution. The prepared kuh-seng base ionic liquid conotoxin polypeptide solution has good stability and biocompatibility, has the effect of slow release and permeation promotion, can be delivered in a percutaneous way, can avoid the degradation of polypeptide drugs under acidic and enzymatic reaction conditions in a digestive system and the first pass effect of a liver in clinical application, and can reduce the influence of skin barrier effect in external application.
Description
Technical Field
The invention relates to the technical field of microemulsion, in particular to a kuh-seng base ionic liquid conotoxin polypeptide solution, a preparation method and application thereof.
Background
The conotoxin polypeptide is a complex short peptide mixture secreted by a Conus geophagus venom tube and a venom gland on the inner wall of a venom sac, is an anesthetic for Conus preys, has strong muscle penetrating power, and has potential application in the aspects of wrinkle reduction and skin tightening. In addition, conotoxin polypeptides are also antagonists of N and NMDA receptors, and in particular the Con-G protein is specific for the NMDA receptor subtype 2B, and thus conotoxin polypeptides are more selective than morphine in the treatment of a variety of diseases and do not become addictive or have side effects over a therapeutic dose range. In addition, due to its association with NMDA receptors, it has potential in the treatment of Alzheimer's disease and Parkinson's disease as a means of alleviating drug-induced withdrawal symptoms.
The oral route of administration remains the most preferred method of administration due to the familiar methods of use, ease of operation and high compliance. However, the polypeptide-based drug is easily degraded by enzymatic reaction in the gastric acid environment, and there is a first-pass effect of the liver. Enzymatic degradation of peptide formulations and liver metabolism can be effectively avoided by transdermal delivery, but they are also poorly affected by skin barrier effects when used externally.
Accordingly, the prior art is yet to be improved and developed.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a kuh-seng base ionic liquid conotoxin polypeptide solution, a preparation method and application thereof, and aims to solve the problems that the existing polypeptide component medicine is easy to degrade through enzymatic reaction in a gastric acid environment when being taken orally, has a first pass effect of liver, and is affected by a skin barrier effect when being taken externally, so that the effect is poor.
The technical scheme of the invention is as follows:
the invention provides a preparation method of a matrine-based ionic liquid conotoxin polypeptide solution, which comprises the following steps:
providing a conotoxin polypeptide mother liquor;
adding matrine and organic acid into water to obtain matrine organic acid ion salt solution;
and mixing the matrine organic acid ionic salt solution and the conotoxin polypeptide mother solution to obtain a matrine ionic liquid conotoxin polypeptide solution.
Optionally, the preparation method of the conotoxin polypeptide mother liquor comprises the following steps:
adding the conotoxin polypeptide into water to obtain a conotoxin polypeptide mother liquor.
Optionally, the organic acid is selected from one or more of saturated fatty acid with C6-C18, unsaturated fatty acid with the unsaturation degree of 1-3, taurine, malic acid and mandelic acid.
Optionally, the amount ratio of the matrine to the organic acid is 1: 1-1: 4.
The second aspect of the invention provides a preparation method of a matrine-based ionic liquid conotoxin polypeptide preparation, wherein the preparation method comprises the following steps:
mixing an emulsifier with an auxiliary agent to obtain a mixed emulsifier solution;
mixing the kuh-seng base ionic liquid conotoxin polypeptide solution with the mixed emulsifier solution to obtain the kuh-seng base ionic liquid conotoxin polypeptide preparation.
Optionally, the emulsifier is selected from one or more of polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol, polyoxyethylene sorbitan fatty acid ester, and/or the auxiliary agent is selected from one or more of n-butyl alcohol, ethylene glycol, ethanol, propylene glycol, glycerol, polyglycerol fatty acid ester, and sorbitol fatty acid ester.
Optionally, the mass ratio of the emulsifier to the auxiliary agent is 1: 0.1-1: 10.
Optionally, the concentration of the conotoxin polypeptide in the kuh-seng base ionic liquid conotoxin polypeptide preparation is 0.0001-10 mg/mL.
The third aspect of the invention provides a kuh-seng base ionic liquid conotoxin polypeptide preparation, wherein the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation is adopted to prepare the preparation.
In a fourth aspect of the present invention, an application of the sophora flavescens base ionic liquid conotoxin polypeptide solution prepared by the above preparation method of the sophora flavescens base ionic liquid conotoxin polypeptide solution in preparation of a drug or a skin care product is provided, or an application of the sophora flavescens base ionic liquid conotoxin polypeptide preparation prepared by the above preparation method of the sophora flavescens base ionic liquid conotoxin polypeptide preparation in preparation of a drug or a skin care product is provided, or an application of the sophora flavescens base ionic liquid conotoxin polypeptide preparation in preparation of a drug or a skin care product is provided.
Has the advantages that: the kuh-seng base ionic liquid conotoxin polypeptide solution prepared by the preparation method has good stability and biocompatibility and a slow-release permeation promoting effect, and the solubility of the conotoxin polypeptide is high, so that the permeation of the conotoxin polypeptide and the absorption of a human body on the conotoxin polypeptide can be effectively improved, the percutaneous route delivery can be carried out, the easy degradation of a polypeptide drug in a digestive system under the conditions of acidity and enzymatic reaction and the first pass effect of a liver in clinical application can be avoided, the incidence rate of adverse reactions is reduced, and the influence of skin barrier effect in external use can be reduced. The kuh-seng base ionic liquid conotoxin polypeptide solution has a slow release effect, so that the stimulation to the skin during transdermal delivery is reduced, the solution is mild, the transdermal absorption is promoted, and the solution is green and safe. In addition, the kuh-seng base ionic liquid conotoxin polypeptide solution has the effects of tightening, resisting wrinkles and resisting aging, and has wide market prospects in various daily chemical articles and preparation formulas.
Drawings
Fig. 1 is a flow chart of preparation of a kuh-seng base ionic liquid conotoxin polypeptide solution in the embodiment of the present invention.
Fig. 2 is a graph showing the skin permeation effect of the blank control group in example 1 of the present invention.
Fig. 3 is a graph showing the skin permeation effect of the conotoxin polypeptide preparation of comparative example 1 of the present invention.
Fig. 4 is a diagram illustrating the skin permeation effect of the kuh-seng base ionic liquid conotoxin polypeptide preparation in example 1 of the present invention.
Fig. 5 is a graph showing the effect of the eye cream in example 3 of the present invention, wherein (a) is a graph showing the effect of the eye cream before use, and (b) is a graph showing the effect of the eye cream after use.
Detailed Description
The invention provides a kuh-seng base ionic liquid conotoxin polypeptide solution, a preparation method and application thereof, and the invention is further detailed below in order to make the purpose, technical scheme and effect of the invention clearer and more clear. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a preparation method of a kuh-seng base ionic liquid conotoxin polypeptide solution, as shown in figure 1, wherein the preparation method comprises the following steps:
s1, providing a conotoxin polypeptide mother solution;
s2, adding matrine and organic acid into water to obtain matrine organic acid ion salt solution;
s3, mixing the matrine organic acid ionic salt solution and the conotoxin polypeptide mother solution to obtain a matrine ionic liquid conotoxin polypeptide solution.
In the embodiment, matrine is taken as a cation precursor, organic acid is taken as an anion precursor, and the matrine organic acid ion salt is synthesized through an ionization salt-forming reaction, wherein the matrine organic acid ion salt is a room-temperature ionic liquid and is a supermolecular material, and the ionic liquid has small vapor pressure, good stability and special solubility on a plurality of inorganic salts and organic matters, so that the matrine organic acid ion salt solution can well dissolve the conotoxin polypeptide, and meanwhile, the matrine ionic liquid can wrap the conotoxin polypeptide to a certain extent to form a micelle, thereby enhancing the stability and promoting the absorption. Mixing the matrine organic acid ion salt solution and the conotoxin polypeptide mother solution to obtain the matrine ionic liquid conotoxin polypeptide solution. The matrine-based ionic liquid conotoxin polypeptide preparation completely reserves the main molecular skeleton of a matrine monomer, so that the solution has the effects of preventing skin psoriasis, resisting inflammation and allergy, promoting collagen generation and whitening. In addition, the kuh-seng base ionic liquid conotoxin polypeptide solution also retains the efficacy of organic acid, the organic acid has strong compatibility with epidermal tissues, ion channels among the epidermal tissues can be effectively opened, and the solution can increase the fluidity of active ingredients such as the conotoxin polypeptide, the matrine and the like in the epidermal tissues when passing through the skin, so that the permeation effect of active substances is further increased.
The preparation method combines the supermolecule material and the conotoxin polypeptide, the prepared kuh-seng base ionic liquid conotoxin polypeptide solution is good in stability and biocompatibility and has the effect of slow release and permeation promotion, the penetration of the conotoxin polypeptide and the absorption of a human body on the conotoxin polypeptide can be effectively improved by the kuh-seng base ionic liquid conotoxin polypeptide solution, oral administration or transdermal delivery can be carried out, the degradation of the polypeptide drug in a digestive system under the conditions of acidity and enzymatic reaction and the first pass effect of a liver in clinical application can be avoided, the incidence rate of adverse reactions is reduced, and the influence of skin barrier effect in external use can be reduced. The solution has sustained release effect to reduce skin irritation during transdermal delivery, is mild and promotes transdermal absorption, and is green and safe. In addition, the preparation has the effects of tightening, resisting wrinkles and resisting aging, and has wide market prospect in various daily chemical products and preparation formulas.
In step S1, in one embodiment, the preparation of the conotoxin polypeptide mother liquor comprises:
adding the conotoxin polypeptide into water to obtain a conotoxin polypeptide mother liquor.
The conotoxin polypeptide is a complex short peptide mixture secreted by a conus venom tube and a venom gland on the inner wall of a venom sac, is an anesthetic for conus preys on prey, has strong muscle penetrating power, and therefore has potential application in wrinkle reduction and skin tightening, is an antagonist of an N receptor and an NMDA receptor, and particularly has a special shape of a Con-G protein to an NMDA receptor 2B subtype, so that the conotoxin polypeptide is more selective in treatment of various diseases than morphine, and does not have addiction or side effect in a treatment dosage range. In addition, due to its involvement in NMDA receptors, it has potential in the treatment of Alzheimer's disease and Parkinson's disease.
In step S2, matrine is used as a cation precursor, an organic acid is used as an anion precursor, and an organic acid salt of matrine is synthesized by an ionization salt-forming reaction, wherein the matrine organic acid ion salt is a room temperature ionic liquid, and the ionic liquid has low vapor pressure, good stability, and special solubility for many inorganic salts and organic substances, so that the solubility of active ingredients can be effectively increased, and the solubility and stability of proteins (e.g., conotoxin polypeptides) can be increased.
Wherein the matrine is an alkaloid extracted from radix Sophorae Flavescentis, and has effects of preventing skin psoriasis, resisting inflammation and allergy, promoting collagen production, and whitening skin. In addition, matrine has antipyretic, analgesic, anticonvulsant, and nerve stabilizing effects on central nervous system; has obvious negative frequency and positive muscle action on cardiovascular system, and has functions of preventing and treating atherosclerosis and relieving myocardial injury; has effects of resisting liver injury and fibrosis on digestive system, and also has anti-tumor and anti-hepatocarcinoma effects.
In one embodiment, the organic acid is selected from one or more of saturated fatty acid with C6-C18, unsaturated fatty acid with the degree of unsaturation of 1-3, taurine, malic acid and mandelic acid, but is not limited thereto.
When the organic acid is selected from saturated or unsaturated fatty acid, it can improve liposolubility and oil solubility of matrine organic acid ion salt. The compatibility of the matrine-based ionic liquid conotoxin polypeptide solution prepared from the matrine organic acid ion salt with epidermal tissues is further enhanced, ion channels among the epidermal tissues are further effectively opened, the fluidity of active ingredients in the epidermal tissues is increased, and the permeation effect of active substances is further increased.
The Taurine (Taurine) is a sulfur-containing amino acid with simple structure in an animal body, has no odor, slightly acidic taste and stable heat, is combined with cholic acid in human and animal bile and exists in a combined form, but exists in free forms in tissues such as brain, ovary, heart, liver, milk, pineal body, pituitary, retina, adrenal gland and the like, does not participate in the synthesis of protein, is an essential amino acid of the human body, and has important effect on the development of the nervous system of fetus and infants.
The malic acid as the main component of apple is widely existed in nature, and is a component widely distributed in human diet. The natural malic acid has various biological activities, and has the functions of eliminating free radicals, resisting oxidation, resisting tumor and inhibiting bacteria, inhibiting obesity, improving emotion and promoting intestinal health in human body and other animals. When the organic acid is selected from malic acid, the composition can promote the exfoliation of keratinocytes, increase skin collagen, and effectively improve the xerosis cutis.
In addition, the organic acid according to this embodiment may be geranic acid.
In one embodiment, the amount ratio of the matrine to the organic acid is 1:1 to 1: 4. The proportion can better realize the ionization modification of the matrine by the organic acid to generate the matrine organic acid ion salt.
In step S3, the step of mixing the matrine organic acid ion salt solution and the conotoxin polypeptide mother liquor to obtain the matrine ionic liquid conotoxin polypeptide solution specifically includes:
under the condition of stirring, dropwise adding the matrine organic acid ion salt solution into the conotoxin polypeptide mother solution, and mixing to obtain the matrine ionic liquid conotoxin polypeptide solution. The matrine organic acid ion salt is room temperature ionic liquid, and the ionic liquid has small vapor pressure, good stability and special solubility to a plurality of inorganic salts and organic matters, so that the matrine organic acid ion salt solution can well dissolve and wrap the conotoxin polypeptide and increase the stability of the conotoxin polypeptide.
The embodiment of the invention also provides a kuh-seng base ionic liquid conotoxin polypeptide solution, wherein the kuh-seng base ionic liquid conotoxin polypeptide solution is prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide solution. The matrine ionic liquid conotoxin polypeptide solution comprises matrine organic acid ion salts, conotoxin polypeptides and water. The kuh-seng base ionic liquid conotoxin polypeptide solution is in a uniform solution state with stable property, is mild and low in stimulation, has better stability and biocompatibility, has the effect of slow release and permeation promotion, and can effectively improve the permeation of the conotoxin polypeptide through the skin and the absorption of the conotoxin polypeptide by a human body. And the matrine-based ionic liquid conotoxin polypeptide solution keeps the main molecular skeleton of the matrine monomer, so that the matrine-based ionic liquid conotoxin polypeptide solution has the effects of preventing skin psoriasis, resisting inflammation and allergy, promoting collagen generation and whitening. Taking malic acid as an example, the characteristics of malic acid for promoting the exfoliation of keratinocytes, increasing skin collagen and effectively improving the phenomenon of dry skin are also retained, and the biological activity and efficacy of matrine and organic acid are retained in the matrine ionic liquid conotoxin polypeptide solution.
The embodiment of the invention also provides a preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation, wherein the preparation method comprises the following steps:
s4, mixing the emulsifier with the auxiliary agent to obtain a mixed emulsifier solution;
s5, mixing the kuh-seng base ionic liquid conotoxin polypeptide solution and the mixed emulsifier solution to obtain the kuh-seng base ionic liquid conotoxin polypeptide preparation.
In step S4, in one embodiment, the emulsifier is selected from one or more of polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol, polyoxyethylene sorbitan fatty acid ester, but is not limited thereto.
In one embodiment, the adjuvant is selected from one or more of n-butanol, ethylene glycol, ethanol, propylene glycol, glycerin, polyglycerin fatty acid ester, sorbitol fatty acid ester, but is not limited thereto.
In one embodiment, the mass ratio of the emulsifier to the auxiliary agent is 1:0.1 to 1: 10. For example, the mass ratio of the emulsifier to the adjuvant can be 1:0.1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, and the like.
In step S5, it should be noted that the emulsifier can wrap the conotoxin polypeptide to form micro-micelles, which further enhances the stability of the conotoxin polypeptide, so that the conotoxin polypeptide can better permeate into the skin, and thus the addition amounts of the emulsifier and the auxiliary agent can be adjusted according to the final permeability of the kuh-seng base ionic liquid conotoxin polypeptide preparation.
And mixing the kuh-seng base ionic liquid conotoxin polypeptide solution with the mixed emulsifier solution to obtain a kuh-seng base ionic liquid conotoxin polypeptide preparation, wherein the kuh-seng base ionic liquid conotoxin polypeptide preparation is in a uniform emulsion state with stable properties.
In one embodiment, the step of mixing the matrine ionic liquid conotoxin polypeptide solution with the mixed emulsifier solution to obtain the matrine ionic liquid conotoxin polypeptide preparation specifically comprises:
and dropwise adding the kuh-seng base ionic liquid conotoxin polypeptide solution into the mixed emulsifier solution under the stirring condition to obtain the kuh-seng base ionic liquid conotoxin polypeptide preparation.
In one embodiment, the concentration of the conotoxin polypeptide in the kuh-seng base ionic liquid conotoxin polypeptide preparation is 0.0001-10 mg/mL. When the concentration of the conotoxin polypeptide is the concentration, the conotoxin polypeptide has better solubility and stability in a kuh-seng base ionic liquid conotoxin polypeptide preparation, and can realize the penetration and absorption of the conotoxin polypeptide on the surface of skin.
The embodiment of the invention also provides a kuh-seng base ionic liquid conotoxin polypeptide preparation, wherein the preparation method is adopted to prepare the kuh-seng base ionic liquid conotoxin polypeptide preparation. The kurarinone base ionic liquid conotoxin polypeptide preparation comprises a kurarinone base organic acid ion salt, conotoxin polypeptide, an emulsifier, an auxiliary agent and water. The kuh-seng base ionic liquid conotoxin polypeptide preparation is mild and low in stimulation, has better stability and biocompatibility, has the effect of slow release and permeation promotion, and can effectively improve the permeation of conotoxin polypeptides through skin and the absorption of conotoxin polypeptides by human bodies. And the matrine-based ionic liquid conotoxin polypeptide preparation keeps the main molecular skeleton of a matrine monomer, so that the matrine-based ionic liquid conotoxin polypeptide preparation has the effects of preventing skin psoriasis, resisting inflammation and allergy, promoting collagen generation and whitening. Taking malic acid as an example, the preparation also keeps the characteristics of malic acid in promoting the exfoliation of keratinocytes, increasing skin collagen and effectively improving the phenomenon of dry skin, and the matrine-based ionic liquid conotoxin polypeptide preparation also keeps the biological activities and efficacies of matrine and organic acid.
The embodiment of the invention also provides application of the kuh-seng base ionic liquid conotoxin polypeptide solution prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide solution in preparation of medicines or skin care products.
The embodiment of the invention also provides application of the sophocarpidine-based ionic liquid conotoxin polypeptide solution in preparation of medicines or skin care products.
The embodiment of the invention also provides application of the kuh-seng base ionic liquid conotoxin polypeptide preparation prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation in preparation of medicines or skin care products.
The embodiment of the invention also provides application of the kuh-seng base ionic liquid conotoxin polypeptide preparation in preparation of medicines or skin care products.
In a specific embodiment, the kuh-seng base ionic liquid conotoxin polypeptide preparation prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation according to the embodiment of the present invention or the kuh-seng base ionic liquid conotoxin polypeptide preparation according to the embodiment of the present invention is used for preparing eye cream or face cream. In a more specific embodiment, the eye cream comprises a matrine-based ionic liquid conotoxin polypeptide preparation, wheat germ oil, sodium hyaluronate, vitamin B1, vitamin E, a surfactant, a co-surfactant and water. The eye cream containing the kuh-seng base ionic liquid conotoxin polypeptide preparation can effectively promote the penetration of functional components, stimulate the regeneration of fibroblasts and produce collagen, thereby restoring the skin elasticity.
The sophocarpidine-based ionic liquid conotoxin polypeptide solution or preparation disclosed by the embodiment of the invention can be combined with other components to prepare skin care products such as but not limited to essence, eye mask essence, emulsion and the like, so that different effects are realized.
The invention is further illustrated by the following specific examples.
Example 1
Adding 0.01mol of matrine and 0.01mol of octanoic acid into a reaction vessel containing 20mL of water, and stirring for 12 hours to obtain matrine organic acid ion salt solution. At room temperature, 0.001g of conotoxin polypeptide is added into 10mL of water and stirred uniformly to obtain a conotoxin polypeptide mother liquor. Under the condition of stirring, dropwise adding the matrine organic acid ion salt solution into the conotoxin polypeptide mother solution to obtain the matrine ionic liquid conotoxin polypeptide solution. At room temperature, mixing the emulsifier polyvinylpyrrolidone and the auxiliary agent sorbitol fatty acid ester according to the molar ratio of 1:1, and fully and uniformly mixing to obtain a mixed emulsifier solution. And taking 4g of mixed emulsifier solution, dropwise adding the kuh-seng base ionic liquid conotoxin polypeptide solution into the 4g of mixed emulsifier solution under the stirring condition, and observing the phenomenon that the system is from turbid to clear or from clear to turbid to obtain the kuh-seng base ionic liquid conotoxin polypeptide preparation.
Example 2
Adding 0.01mol of matrine and 0.01mol of malic acid into a reaction vessel containing 20mL of water, and stirring for 12 hours to obtain matrine organic acid ion salt solution. At room temperature, 0.100g of conotoxin polypeptide is added into 10mL of water and stirred uniformly to obtain a conotoxin polypeptide mother liquor. Under the condition of stirring, dropwise adding the matrine organic acid ion salt solution into the conotoxin polypeptide mother solution to obtain the matrine ionic liquid conotoxin polypeptide solution. At room temperature, 0.848g of emulsifier polyvinyl alcohol and auxiliary agent sorbitol fatty acid ester are mixed according to the molar ratio of 1:1 and are fully and uniformly mixed to obtain mixed emulsifier solution. Taking 4g of mixed emulsifier solution, dropwise adding the kuh-seng base ionic liquid conotoxin polypeptide solution into 4g of mixed emulsifier solution under the condition of stirring, and observing the phenomenon that the system is from turbid to clear or from clear to turbid to obtain the kuh-seng base ionic liquid conotoxin polypeptide preparation.
Comparative example 1
Preparing a conotoxin polypeptide preparation:
the conotoxin polypeptide preparation does not contain matrine component, and the preparation method is the same as example 1, except that matrine is not added.
The kushene base ionic liquid conotoxin polypeptide preparation in example 1 and the conotoxin polypeptide preparation in comparative example 1 are subjected to a transdermal delivery effect test
The results of the tests are shown in table 1 below and in figures 2-4 after 1 hour of exposure of the samples to the epidermis model.
Table 1: osmotic concentration of different conotoxin polypeptide preparations
From the results in table 1, it can be seen that the mean penetration amount of the conotoxin polypeptide preparation group (comparative example 1) was 0.38 μ g/mL and the mean penetration amount of the kurarinone ionic liquid conotoxin polypeptide preparation group (example 1) was 0.71 μ g/mL after the samples were applied to the epidermal model for 1 hour. The skin model microscope observation shows that the penetration depth of the conotoxin polypeptide in the kuh-seng base ionic liquid conotoxin polypeptide preparation group (example 1) is obviously increased (as shown in figure 4), and the penetration depth is obviously greater than that of the conotoxin polypeptide preparation group (comparative example 1, as shown in figure 3). The results prove that the kuh-seng base ionic liquid conotoxin polypeptide preparation effectively breaks through ion channels between epidermal tissues, increases the fluidity and permeability of the conotoxin polypeptide in the epidermal tissues, and means the increase of the efficacy of the preparation.
Example 3
The preparation of the anti-wrinkle tightening eye cream containing the kuh-seng base ionic liquid conotoxin polypeptide preparation comprises the following steps:
the preparation method comprises the following steps of: 0.1% of the kuh-seng base ionic liquid conotoxin polypeptide preparation in the embodiment 1, 2.5% of wheat germ oil, 0.5% of sodium hyaluronate, 0.01% of vitamin B1, 0.01% of vitamin E, 2.0% of surfactant, 0.5% of cosurfactant and the balance of water, so as to obtain the anti-wrinkle and firming eye cream containing the kuh-seng base ionic liquid conotoxin polypeptide preparation. And the practical use test is carried out on the anti-wrinkle and firming eye cream, the anti-wrinkle and firming eye cream is coated around the eyes of a tester with wrinkles around the eyes, the test results of the anti-wrinkle and firming eye cream are shown in (a) and (b) in fig. 5, and the anti-wrinkle effect is obvious after the eye cream is used for 10 min. The kuh-seng base ionic liquid conotoxin polypeptide preparation can effectively promote the penetration of functional components, stimulate the regeneration of fibroblasts and produce collagen, thereby restoring the elasticity of the skin.
In summary, the invention provides a kuh-seng base ionic liquid conotoxin polypeptide solution, a preparation method and an application thereof, the kuh-seng base ionic liquid conotoxin polypeptide solution and the preparation prepared by the preparation method have good stability and biocompatibility, have a slow-release permeation promoting effect, have high solubility of conotoxin polypeptides, can effectively improve the permeation of the conotoxin polypeptides and the absorption of the conotoxin polypeptides by a human body, can carry out transdermal delivery, can avoid the degradation of polypeptide drugs easily under the acidic and enzymatic reaction conditions in a digestive system and the first pass effect of a liver in clinical application, reduce the incidence of adverse reactions, and can reduce the influence of skin barrier effect in external use. The kuh-seng base ionic liquid conotoxin polypeptide solution and the preparation have a slow release effect, so that the stimulation to the skin during transdermal delivery is reduced, the solution is mild, the transdermal absorption is promoted, and the solution is green and safe. In addition, the kuh-seng base ionic liquid conotoxin polypeptide solution and the preparation have the effects of tightening, resisting wrinkles and resisting aging, and have wide market prospects in various daily chemical articles and preparation formulas.
It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.
Claims (10)
1. A preparation method of a kuh-seng base ionic liquid conotoxin polypeptide solution is characterized by comprising the following steps:
providing a conotoxin polypeptide mother liquor;
adding matrine and organic acid into water to obtain matrine organic acid ion salt solution;
and mixing the matrine organic acid ionic salt solution and the conotoxin polypeptide mother solution to obtain a matrine ionic liquid conotoxin polypeptide solution.
2. The method for preparing the sophocarpidine-based ionic liquid conotoxin polypeptide solution as claimed in claim 1, wherein the preparation of the conotoxin polypeptide mother liquor comprises the steps of:
adding the conotoxin polypeptide into water to obtain a conotoxin polypeptide mother liquor.
3. The method for preparing the sophocarpidine-based ionic liquid conotoxin polypeptide solution according to claim 1, wherein the organic acid is selected from one or more of saturated fatty acids of C6-C18, unsaturated fatty acids with unsaturation degree of 1-3, taurine, malic acid and mandelic acid.
4. The preparation method of the matrine-based ionic liquid conotoxin polypeptide solution as claimed in claim 1, wherein the amount ratio of the matrine to the organic acid is 1: 1-1: 4.
5. A preparation method of a kuh-seng base ionic liquid conotoxin polypeptide preparation is characterized by comprising the following steps:
mixing an emulsifier with an auxiliary agent to obtain a mixed emulsifier solution;
mixing the matrine ionic liquid conotoxin polypeptide solution of claim 1 with the mixed emulsifier solution to obtain the matrine ionic liquid conotoxin polypeptide preparation.
6. The preparation method of the matrine-based ionic liquid conotoxin polypeptide preparation of claim 5, wherein the emulsifier is selected from one or more of polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol, polyoxyethylene sorbitan fatty acid ester, and/or,
the auxiliary agent is one or more selected from n-butanol, ethylene glycol, ethanol, propylene glycol, glycerol, polyglyceryl fatty acid ester and sorbitol fatty acid ester.
7. The preparation method of the matrine-based ionic liquid conotoxin polypeptide preparation as claimed in claim 5, wherein the mass ratio of the emulsifier to the auxiliary agent is 1: 0.1-1: 10.
8. The method for preparing the kuh-seng base ionic liquid conotoxin polypeptide preparation as claimed in claim 5, wherein the concentration of conotoxin polypeptide in the kuh-seng base ionic liquid conotoxin polypeptide preparation is 0.0001-10 mg/mL.
9. A kuh-seng base ionic liquid conotoxin polypeptide preparation, which is characterized by being prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation as claimed in any one of claims 5 to 8.
10. An application of the kuh-seng base ionic liquid conotoxin polypeptide solution prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide solution according to any one of claims 1 to 4 in preparation of a medicament or a skin care product, an application of the kuh-seng base ionic liquid conotoxin polypeptide preparation prepared by the preparation method of the kuh-seng base ionic liquid conotoxin polypeptide preparation according to any one of claims 5 to 8 in preparation of a medicament or a skin care product, or an application of the kuh-seng base ionic liquid conotoxin polypeptide preparation according to claim 9 in preparation of a medicament or a skin care product.
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