CN110664646A - Composition with whitening effect, high-drug-loading-rate whitening soluble microneedle patch and preparation method thereof - Google Patents
Composition with whitening effect, high-drug-loading-rate whitening soluble microneedle patch and preparation method thereof Download PDFInfo
- Publication number
- CN110664646A CN110664646A CN201911115373.2A CN201911115373A CN110664646A CN 110664646 A CN110664646 A CN 110664646A CN 201911115373 A CN201911115373 A CN 201911115373A CN 110664646 A CN110664646 A CN 110664646A
- Authority
- CN
- China
- Prior art keywords
- parts
- whitening
- microneedle
- soluble
- hyaluronic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0061—Methods for using microneedles
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Abstract
The invention relates to a composition with a whitening effect, a high-drug-loading-rate whitening soluble microneedle patch and a preparation method thereof. The composition with the whitening effect comprises the following components in parts by weight: 10-20 parts of arbutin, 10-20 parts of magnesium ascorbyl phosphate, 5-10 parts of adenosine and 0.1-0.5 part of sturgeon caviar extract. The whitening soluble microneedle patch consists of a needle point and a substrate, wherein the needle point is prepared from the composition with the whitening effect, hyaluronic acid or sodium salt thereof and microneedle accessories; the composition with the whitening effect, the hyaluronic acid or sodium salt thereof and the microneedle auxiliary material are in a mass ratio of 1:0.1-5: 0.2-1; the microneedle auxiliary material consists of polyvinylpyrrolidone, glycerol and hydroxypropyl cellulose. The whitening soluble microneedle patch has high drug loading capacity, excellent mechanical performance and high whitening, spot-lightening and moisturizing effects.
Description
Technical Field
The invention belongs to the field of microneedles, and particularly relates to a composition with a whitening effect, a high-drug-loading-rate whitening soluble microneedle patch and a preparation method thereof.
Background
The color spot is a general name of all dark spots formed on the skin by stimulation of various adverse factors of the internal and external world, and is mostly a pigmentation spot which is formed by increasing or eliminating the synthesis of melanin on the surface layer of the skin slowly to become brown or black. The color spots are more frequent on the cheeks and forehead, which seriously affects the beauty of the face. The whitening and spot-lightening products sold in the market nowadays usually achieve the whitening and spot-lightening effect by adding skin whitening agents into the products, and the action mechanism of the skin whitening agents is that tyrosinase is taken as a target point, and tyrosinase activity, synthesis and migration are inhibited, or melanocyte is cytotoxic so as to inhibit melanosis. However, the skin is a complex tissue structure, and the stratum corneum is the main barrier for the penetration of active ingredients, so that most ingredients, particularly water-soluble ingredients, cannot well penetrate into subcutaneous tissues to play a role. Common effective skin whitening agents such as kojic acid, arbutin, ascorbic acid, ferulic acid and the like have the problems of poor skin permeability and poor stability in water or air, cannot exert the maximum efficacy when added into the traditional cosmetic formulations such as cream, water, milk and the like, and have unobvious whitening and spot-lightening effects.
Microneedle cosmetic therapy is a modern cosmetic method, and microneedles can be divided into solid microneedles, hollow microneedles, coated microneedles and soluble microneedles. Compared to soluble microneedles, coated, hollow, and solid microneedles are relatively simple to fabricate, but have respective drawbacks, such as: the coating micro-needle has small drug loading, and the coating metering is difficult to accurately control; the micro-channel is easy to close quickly after the solid micro-needle is pretreated, the effect is poor, and the micro-channel has the risk of residual harmful substances after the needle head is broken like the hollow micro-needle. Although a large amount of solid microneedles and hollow microneedles are put into use at present, more and more researches are carried out on soluble microneedles, the soluble microneedle technology is a novel microneedle technology for directly dissolving effective components into skin, and the problem of poor skin permeability and stability of the active components can be solved by applying the soluble microneedle technology to a whitening and spot-fading product. The soluble micro-needle can form a self-repairing micro-channel after penetrating into the skin, and the skin is not hardened to cause skin contraction by utilizing the natural healing capacity of the wound; a large number of nano-scale channels are generated in the skin, so that the effective components can be quickly dissolved and permeated in the body, and the transdermal transfer efficiency of macromolecules and water-soluble medicines is greatly improved; the effect exceeds that of the traditional whitening spot-lightening product, and the whitening spot-lightening product is safe, has small irritation, strong and lasting effect and unlimited market potential.
However, in general, a high amount of an active ingredient added directly affects the mechanical properties of soluble microneedles, resulting in low strength and poor toughness of the microneedles, and the microneedles cannot penetrate the skin and thus cannot exert their effects, so that many of the conventional soluble microneedles have a problem of low drug loading.
Disclosure of Invention
Based on the above, the present invention aims to provide a high drug-loading whitening soluble microneedle patch to solve the above problems.
In order to achieve the purpose, the invention firstly provides a composition with whitening effect, the composition has good whitening, spot-lightening or spot-removing effects, and the composition can be combined with specific microneedle auxiliary materials to prepare a high-drug-loading-rate whitening soluble microneedle patch which has good effects of whitening skin and removing spots.
The specific technical scheme is as follows:
the composition with the whitening effect comprises the following components in parts by weight:
10-20 parts of arbutin, 10-20 parts of magnesium ascorbyl phosphate, 5-10 parts of adenosine and 0.1-0.5 part of sturgeon caviar extract.
In some embodiments, the composition with whitening effect comprises the following components in parts by weight:
11-15 parts of arbutin, 13-17 parts of magnesium ascorbyl phosphate, 6-8 parts of adenosine and 0.1-0.5 part of sturgeon caviar extract.
The composition with whitening effect of the invention comprises the following components: arbutin, a natural active substance derived from green plants, can rapidly permeate into skin, can effectively inhibit the activity of tyrosinase in the skin and block the formation of melanin while not influencing the cell proliferation concentration, accelerates the decomposition and excretion of the melanin by directly combining with the tyrosinase, thereby reducing the skin pigmentation, removing color spots and freckles, does not generate toxic, irritant, sensitizing and other side effects on the melanocyte, and has the functions of sterilization and inflammation diminishing. The magnesium ascorbyl phosphate can effectively resist ultraviolet invasion, capture oxygen free radicals, promote collagen generation, prevent pigmentation, fade various skin stains, and enable skin to be moist, white, tender and smooth. Adenosine can supplement skin energy, remarkably improve skin elasticity, promote skin cell metabolism, prevent skin tissue relaxation, reorganize skin structure, and restore skin elasticity by tightening and shrinking pores. The sturgeon caviar extract contains polypeptide as active ingredient, and has effects of nourishing inner skin, improving dark yellow, sensitive and red blood streak symptoms of skin, and removing pigmentation and senile plaque; meanwhile, the skin is compact and contains moisture-retaining components, so that moisture is retained for a long time, and the skin is tender and smooth; but also can enhance the skin immunity, improve the ability of the skin to resist external stimulation, improve the health condition of the skin and lead the skin to be white, red and transparent. The components are used together, so that the synergistic effect is achieved, and the obtained composition has excellent effects of whitening skin and removing color spots.
The invention also provides application of the composition with the whitening effect.
The specific technical scheme is as follows:
the composition is applied to preparing whitening skin care products or whitening cosmetics.
The invention also provides a whitening soluble microneedle patch with high drug loading capacity.
The technical scheme is as follows:
a high drug-loading whitening soluble microneedle patch consists of a needle point and a substrate, wherein the needle point is prepared from an active ingredient, hyaluronic acid or sodium salt thereof and microneedle accessories;
the mass ratio of the active ingredient, hyaluronic acid or sodium salt thereof and the microneedle auxiliary material is 1:0.1-5: 0.2-1;
the active ingredient is the composition with the whitening effect;
the microneedle auxiliary material consists of polyvinylpyrrolidone, glycerol and hydroxypropyl cellulose.
In some embodiments, the mass ratio of the active ingredient to the hyaluronic acid or sodium salt thereof to the microneedle adjuvant is 1:0.2-3: 0.5-0.8.
In some embodiments, the mass ratio of the active ingredient to the hyaluronic acid or sodium salt thereof to the microneedle adjuvant is 1:0.3-2: 0.5-0.8.
In some embodiments, the mass ratio of the active ingredient to the hyaluronic acid or sodium salt thereof to the microneedle adjuvant is 1:0.4-0.8: 0.6-0.7.
In some implementations, the microneedle adjuvant consists of the following components in parts by weight:
5-15 parts of polyvinylpyrrolidone, 10-20 parts of glycerol and 5-10 parts of hydroxypropyl cellulose.
In some implementations, the microneedle adjuvant consists of the following components in parts by weight:
5-7 parts of polyvinylpyrrolidone, 10-14 parts of glycerol and 5-7 parts of hydroxypropyl cellulose.
In some of these implementations, the hyaluronic acid or sodium salt thereof has a molecular weight of 50kDa to 350 kDa.
In some of these implementations, the hyaluronic acid or sodium salt thereof has a molecular weight of 260kDa to 300 kDa.
In some of these implementations, the substrate is prepared from hyaluronic acid or a sodium salt thereof, glycerol, and hydroxypropyl cellulose.
In some of these implementations, the substrate is prepared from 0.8-1.5 parts hyaluronic acid or its sodium salt, 0.05-0.15 parts glycerol, and 0.05-0.15 parts hydroxypropyl cellulose.
In some of these implementations, the needle tip is conical or cone-like.
The invention also provides a preparation method of the high drug-loading whitening soluble microneedle patch.
The specific technical scheme is as follows:
a preparation method of a high drug-loading whitening soluble microneedle patch comprises the following steps:
(1) preparing a needle tip: uniformly mixing the active ingredients, hyaluronic acid or sodium salt thereof and microneedle accessories, adding water, stirring and dissolving to obtain a needle point solution; pouring the needle point solution into a microneedle mould, and pressurizing to enable the needle point solution to fill the needle hole of the microneedle mould;
(2) preparing a substrate: dissolving a material for preparing a substrate by using water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step (1), drying, and demoulding to obtain the high drug-loading whitening soluble microneedle patch.
In some of these embodiments, the pressurization pressure is 0.02 to 0.06 MPa.
In some of these embodiments, the drying conditions comprise: the temperature is 25 +/-3 ℃, the humidity is 10% +/-5%, and the time is 15 +/-3 h.
The high drug-loading whitening soluble microneedle patch has the advantages that:
according to the invention, arbutin, magnesium ascorbyl phosphate, adenosine and sturgeon caviar extracts are selected to be compounded in a certain proportion as active ingredients, and hyaluronic acid or sodium salt thereof with a certain molecular weight and a certain amount of polyvinylpyrrolidone, glycerol and hydroxypropyl cellulose are used as microneedle accessories, so that the content of the active ingredients in a soluble microneedle product can be greatly increased, and the mechanical properties of the soluble microneedle can be improved, and the prepared whitening soluble microneedle has higher drug loading capacity and excellent mechanical properties. Therefore, the skin whitening and spot-lightening active ingredients (arbutin, magnesium ascorbyl phosphate, adenosine and sturgeon caviar extract) with the needle points of the micro needles are quickly dissolved in the skin and absorbed by the dermis, the activity of tyrosinase in the skin is effectively inhibited, the formation of melanin is blocked, the decomposition and excretion of the melanin are accelerated, the skin pigmentation is reduced, and the effects of whitening the skin and removing spots are achieved.
According to the active ingredients of the soluble microneedle, hyaluronic acid or sodium salt thereof with a certain molecular weight is added into the microneedle auxiliary material, so that the mechanical property and drug-loading capacity of the soluble microneedle can be greatly improved. Meanwhile, hyaluronic acid or sodium salt thereof is an inherent component in a human body, is a glucan aldehyde acid, has no species specificity, the moisture level of the skin is closely related to the content of hyaluronic acid, and the content of hyaluronic acid in the skin is reduced along with the increase of age, so that the water retention function of the skin is weakened, and wrinkles are generated. Hyaluronic acid or sodium salt thereof is used as a microneedle auxiliary material and can play a role of an active ingredient at the same time, other active ingredients are matched and are penetrated into the skin in a microneedle mode, and the small molecular hyaluronic acid can permeate into the dermis layer to promote blood microcirculation, is beneficial to the absorption of nutrients by the skin, further improves the effects of whitening and spot lightening, and can promote the supply of skin nutrition and the excretion of waste so as to prevent skin aging.
The prepared whitening soluble microneedle can quickly transfer active ingredients into the skin in a solid state form, and quickly plays the functions of removing freckles and beautifying. The active ingredients in the microneedle exist in a solid state, so that the stability of the microneedle is greatly improved, and the addition of antiseptic and fungus-inhibiting raw materials is avoided. In addition, the transdermal mode of the soluble micro-needle greatly improves the transdermal absorption rate of the whitening and freckle-removing active substance, does not need to add any bacteriostatic component, and can improve the safety of the product. In addition, the soluble microneedle can realize directional delivery in the skin, so that the use amount of active ingredients is small, the effect is good, the treatment cost is reduced, the market prospect is good, and the expected economic benefit is high.
Drawings
Fig. 1 is a schematic view of a high drug-loading whitening soluble microneedle patch of the present invention, wherein B is a partially enlarged view of a.
Detailed Description
In order that the invention may be more readily understood, reference will now be made to the following more particular description of the invention, examples of which are set forth below. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. These embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The present invention will be described in further detail with reference to specific examples.
The raw materials used in the embodiment of the invention are as follows:
arbutin, west ampere chun biotechnology limited;
magnesium ascorbyl phosphate, showa electric corporation;
adenosine, Wuhan Yuancheng science and technology development Co., Ltd;
sturgeon caviar extract, guangzhou hua Yang biotechnology limited;
sodium hyaluronate with molecular weight of 280kDa, SiAnmeichuan biotechnology Limited;
sodium hyaluronate, molecular weight 400kDa, huaxi biotechnology limited;
polyvinylpyrrolidone, molecular weight 1300kDa, manufactured by shanghai ltd, chemical trade of asian blue;
glycerol, PTNUBIKAJAYA;
hydroxypropyl cellulose, ashland chemical trade Shanghai Co., Ltd.
Example 1
The high drug-loading whitening soluble microneedle patch provided by the embodiment comprises a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 106.2 parts of sodium hyaluronate (molecular weight of 280kDa), 6 parts of polyvinylpyrrolidone (molecular weight of 1300kDa), 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280Kda), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Example 2
The high drug-loading whitening soluble microneedle patch provided by the embodiment comprises a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 70.8 parts of hyaluronic acid (molecular weight of 280kDa), 6 parts of polyvinylpyrrolidone (molecular weight of 1300kDa), 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Example 3
The high drug-loading whitening soluble microneedle patch provided by the embodiment comprises a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 35.4 parts of hyaluronic acid (molecular weight of 280kDa), 6 parts of polyvinylpyrrolidone (molecular weight of 1300kDa), 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Example 4
The high drug-loading whitening soluble microneedle patch provided by the embodiment comprises a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 17.7 parts of hyaluronic acid (molecular weight of 280kDa), 6 parts of polyvinylpyrrolidone (molecular weight of 1300kDa), 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Example 5
The high drug-loading whitening soluble microneedle patch provided by the embodiment comprises a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 11.8 parts of hyaluronic acid (molecular weight of 280kDa), 6 parts of polyvinylpyrrolidone (molecular weight of 1300kDa), 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Comparative example 1
The high drug-loading whitening soluble microneedle patch consists of a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 35.7 parts of beta-cyclodextrin and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Comparative example 2
The high drug-loading whitening soluble microneedle patch consists of a needle tip and a substrate; the needle tip comprises the following raw materials (in parts by weight): 13 parts of arbutin, 15 parts of magnesium ascorbyl phosphate, 7 parts of adenosine, 0.4 part of sturgeon caviar extract, 17.7 parts of hyaluronic acid (molecular weight of 400kDa), 6 parts of polyvinylpyrrolidone, 12 parts of glycerol and 6 parts of hydroxypropyl cellulose; the raw material composition of the substrate is as follows: 1.1 parts of sodium hyaluronate (molecular weight of 280kDa), 0.1 part of glycerol and 0.1 part of hydroxypropyl cellulose.
The preparation method of the high drug-loading whitening soluble microneedle patch provided by the embodiment is as follows:
s1: preparing a needle tip: uniformly mixing the raw materials for preparing the needle tip, adding 591.4 parts of distilled water, stirring and dissolving to obtain a needle tip solution; pouring the prepared needle point solution into a microneedle mould, and pressurizing to 0.04Mpa to enable the needle point solution to fill the needle hole of the microneedle mould;
s2: manufacturing a microneedle substrate: and (3) stirring and dissolving the material for preparing the substrate by using 20 parts of distilled water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step S1, drying at the temperature of 25 +/-3 ℃ and the relative humidity of 10 +/-5% for 15 +/-3 hours, and demoulding to obtain the whitening soluble microneedle patch with high drug loading capacity.
Example 6
The whitening soluble microneedle patches prepared in examples 1 to 5 and comparative examples 1 to 2 were tested for mechanical properties.
In conjunction with the actual use of the microneedles, the microneedles need to be sufficiently stiff to penetrate the skin, while at the same time they need to be sufficiently malleable to ensure that they do not break during penetration through the skin. Therefore, the mechanical property test of the microneedle mainly comprises the hardness and the ductility test of the microneedle by using a texture analyzer.
The test method comprises the following steps: the microneedle patch was placed with its tip facing up on a horizontal test platform, and an axial vertical force was applied through a P/6 type flat-headed stainless steel cylindrical probe at a steady speed of 0.1mm/sec with an excitation force of 0.05N, and the measurement parameters were set as in table 1. The analyzer records the mechanical change during the time the probe contacts the needle tip until a preset height (microneedle height 400 μm) is reached.
TABLE 1 Equipment parameters
The test results are shown in table 2. The results showed that the dissolvable microneedle patches prepared in examples 1-5 all had better hardness than those of comparative examples 1-2. Compared with example 4, the drug loading rate of the comparative example 1 is the same, but the types of the auxiliary materials are different, the hardness of the auxiliary materials is far smaller than that of the example 4, which shows that the types of the micro-needle auxiliary materials have great influence on the drug loading rate and the mechanical property of the micro-needle, and the drug loading rate can be improved without influencing the mechanical property only by selecting proper micro-needle auxiliary materials to be matched with the active component of the invention, and even the mechanical property can be improved within a certain range. Compared with example 4, the drug loading of comparative example 2 is the same, but the molecular weight of hyaluronic acid is different, and the hardness of hyaluronic acid is much lower than that of example 4, which shows that the molecular weight of hyaluronic acid can influence the mechanical performance and the drug loading of the microneedle, and the molecular weight of the invention is selected, so that the drug loading can be improved while the mechanical performance of the microneedle is improved. It can be seen from the data of examples 1-5 that the microneedles prepared by using arbutin, magnesium ascorbyl phosphate, adenosine and sturgeon caviar extract in a specific ratio as active ingredients, hyaluronic acid, polyvinylpyrrolidone, glycerol and hydroxypropyl cellulose in a specific ratio as microneedle adjuvants and matching with a proper molecular weight of hyaluronic acid can obtain good mechanical properties, have good hardness and ductility within the drug-loading range of examples 1-5, and can meet the use requirements of soluble microneedles. In the drug loading range of examples 1 to 5, the hardness of the microneedle is increased and then decreased with the increase of the drug loading, the ductility of the microneedle is slightly decreased with the increase of the drug loading, but the difference is not large, and the whitening soluble microneedle patch prepared in example 4 has the best mechanical property through comparison.
TABLE 2 mechanical Property test results
Example 7 human test
1. Instrument for test
Skin melanin and heme tester for testing melanin content of skin. The instrument mainly determines the content of melanin in the skin by measuring the content of reflected light with specific wavelength irradiated on the skin of a human body. The emitter of the instrument probe emits light with three wavelengths to the skin surface, and the receiver detects the light reflected by the skin. Since the amount of emitted light is constant, the amount of light absorbed by the skin can be measured. The measurement results are expressed as Melanin Index (MI) values and the measurement results are expressed by the L a b system of the international commission on illumination. Higher measured values indicate higher melanin content in the skin.
2. Test volunteer
The method comprises the steps of selecting females with age range of 21-40 years and female volunteers with color spots for 200 persons, dividing test subjects into 2 groups according to test requirements, respectively using 2 different whitening and freckle removing products, dividing each group into 5 groups, and dividing each group into 20 persons. And dividing a test area for a subject, and testing after uniformly and gently cleaning a test part.
3. Testing the environmental requirements of the test
Constant temperature and humidity environment, temperature: 22 ± 1 ℃, humidity: 50 +/-5%. The subject waits for 20-30min in this environment before testing.
4. Test method
Whitening soluble microneedle patches were prepared according to the method of example 4, and shanno arbutin whitening and moisturizing essence milk purchased on the market as test sample 1 and test sample 2, respectively. The test subjects used the whitening dissolvable microneedle patch 3 times a week for a period of 8 weeks. Correspondingly, the test subjects used the shanno arbutin whitening and moisturizing essence milk, which was applied 3 times per week for 8 weeks. During the test period, the tester did not change the daily cleaning habits, but the test site could not use any other cosmetic.
5. Detection method
The test is carried out for five times in total, and divided into using microneedle patches and coating the shanno arbutin whitening and moisturizing essence milk, and the previous 0 week, 1 week, 2 week, 4 week and 8 week are carried out with return visit at the same time every week. Before the test, the testers clean the tested part, sit still for 10-20min, and the experimenters use the test instrument to acquire data of the tested part.
6. Detecting data
(1) Skin melanin content MI value: the MI value represents a melanin index, and the principle thereof is to irradiate human skin with light of a specific wavelength, collect the amount of reflected light, and determine the melanin content in the skin, wherein the larger the MI value is, the higher the melanin content in the skin is. The results are shown in Table 3.
(2) Skin brightness L value: l is white balance, the larger the value, the whiter the skin color, whereas the skin is biased towards black. The results are shown in Table 4.
(3) ITA ° values: the ITA ° values are skin individual type angles and are values that characterize skin brightness associated with L and b (b is blue yellow, + b is yellow, -b is blue). The larger the ITA value is, the brighter the skin is, and conversely, the more the skin is dull. The calculation formula for the ITA ° value is as follows:
the results are shown in Table 5.
TABLE 3 Effect of microneedle patch on skin melanin content MI values
Table 4 effect of microneedle patch on skin brightness L value
Table 5 effect of microneedle patch on ITA ° values
The above test results show that: in the experimental period from 0 to 8 weeks, after the whitening soluble microneedle patch disclosed by the invention is used, the skin brightness L value and the ITA value tend to rise, the rising speed is higher than that of the commercially available Muno-arbutin whitening and moisturizing essence milk, the MI value tends to decrease, the decreasing speed is higher than that of the commercially available Muno-arbutin whitening and moisturizing essence milk, the skin color is biased to white, and the melanin content tends to decrease.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. The composition with the whitening effect is characterized by comprising the following components in parts by weight:
10-20 parts of arbutin, 10-20 parts of magnesium ascorbyl phosphate, 5-10 parts of adenosine and 0.1-0.5 part of sturgeon caviar extract.
2. The composition with whitening effect according to claim 1, characterized by comprising the following components in parts by weight:
11-15 parts of arbutin, 13-17 parts of magnesium ascorbyl phosphate, 6-8 parts of adenosine and 0.1-0.5 part of sturgeon caviar extract.
3. The high drug-loading whitening soluble microneedle patch is characterized by consisting of a needle point and a substrate, wherein the needle point is prepared from an active ingredient, hyaluronic acid or sodium salt thereof and microneedle accessories;
the mass ratio of the active ingredient, hyaluronic acid or sodium salt thereof and the microneedle auxiliary material is 1:0.1-5: 0.2-1;
the active ingredient is the composition with whitening effect according to claim 1 or 2;
the microneedle auxiliary material consists of polyvinylpyrrolidone, glycerol and hydroxypropyl cellulose.
4. The high drug loading whitening soluble microneedle patch as claimed in claim 3, wherein the mass ratio of the active ingredient, hyaluronic acid or sodium salt thereof and microneedle adjuvants is 1:0.2-3: 0.5-0.8.
5. The high drug loading whitening soluble microneedle patch as claimed in claim 4, wherein the mass ratio of the active ingredient, hyaluronic acid or sodium salt thereof and microneedle adjuvants is 1:0.4-0.8: 0.6-0.7.
6. The high drug loading whitening soluble microneedle patch as claimed in any one of claims 3 to 5, wherein the microneedle adjuvant consists of the following components in parts by weight:
5-15 parts of polyvinylpyrrolidone, 10-20 parts of glycerol and 5-10 parts of hydroxypropyl cellulose.
7. The high drug loading whitening soluble microneedle patch as claimed in claim 6, wherein the microneedle adjuvants comprise the following components in parts by weight:
5-7 parts of polyvinylpyrrolidone, 10-14 parts of glycerol and 5-7 parts of hydroxypropyl cellulose.
8. The high drug loading whitening soluble microneedle patch according to any one of claims 3 to 5, wherein the hyaluronic acid or a sodium salt thereof has a molecular weight of 50kDa to 350 kDa.
9. The high drug loading whitening soluble microneedle patch according to claim 8, wherein the molecular weight of hyaluronic acid or its sodium salt is 260kDa-300 kDa.
10. A method for preparing a high drug loading whitening soluble microneedle patch according to any one of claims 3 to 9, comprising the steps of:
(1) preparing a needle tip: uniformly mixing the active ingredients, hyaluronic acid or sodium salt thereof and microneedle accessories, adding water, stirring and dissolving to obtain a needle point solution; pouring the needle point solution into a microneedle mould, and pressurizing to enable the needle point solution to fill the needle hole of the microneedle mould;
(2) preparing a substrate: dissolving a material for preparing a substrate by using water to obtain a substrate solution, uniformly coating the substrate solution in the microneedle mould treated in the step (1), pressurizing, drying and demoulding to obtain the high drug-loading whitening soluble microneedle patch.
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Effective date of registration: 20231126 Address after: 510006 Room 501, floor 2, building 1, No. 1078, Xingye Avenue East, Hualong Town, Panyu District, Guangzhou, Guangdong Province Patentee after: NEWORLD PHARMACEUTICAL Co.,Ltd. Address before: 510663 Room 411, building G2, 31 Kefeng Road, Huangpu District, Guangzhou City, Guangdong Province Patentee before: GUANGZHOU XINJI WEINA BIOTECHNOLOGY CO.,LTD. |