CN107375008B - Soluble microneedle patch for whitening and preparation method thereof - Google Patents

Soluble microneedle patch for whitening and preparation method thereof Download PDF

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CN107375008B
CN107375008B CN201710591732.6A CN201710591732A CN107375008B CN 107375008 B CN107375008 B CN 107375008B CN 201710591732 A CN201710591732 A CN 201710591732A CN 107375008 B CN107375008 B CN 107375008B
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hyaluronic acid
microneedle patch
arbutin
whitening
salt
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CN107375008A (en
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陈航平
李革
郑腾羿
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Guangzhou Xinji Weina Biotechnology Co ltd
Neworld Pharmaceutical Co ltd
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Guangzhou Xinji Weina Biotechnology Co ltd
Neworld Pharmaceutical Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • A61K8/602Glycosides, e.g. rutin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/731Cellulose; Quaternized cellulose derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/735Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/78Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782Enzyme inhibitors; Enzyme antagonists
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91Injection

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  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Dermatology (AREA)
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Abstract

The invention relates to a soluble microneedle patch for whitening and a preparation method thereof. The soluble microneedle patch comprises a needle tip and a substrate, wherein the needle tip is prepared from the following raw materials in parts by weight: 1 part of arbutin, 15-30 parts of hyaluronic acid or salt thereof and 5-25 parts of excipient; the hyaluronic acid or the salt thereof is hyaluronic acid or sodium hyaluronate; the excipient material is at least one of fructose, mannose, sodium carboxymethyl cellulose and hydroxypropyl methylcellulose. The soluble microneedle patch has good mechanical strength, hardness and solubility, avoids the defect that the advantages of arbutin cannot be exerted in the traditional skin care mode, and has remarkable effects of fading color spots and whitening skin.

Description

Soluble microneedle patch for whitening and preparation method thereof
Technical Field
The invention relates to the field of skin care products, in particular to a soluble microneedle patch for whitening and a preparation method thereof.
Background
The microneedle transdermal drug delivery technology is a novel drug delivery mode developed under the condition that the micro-electro-mechanical system processing technology and the transdermal penetration technology are increasingly mature. The micro-needle array has the advantages of small size, high strength, capability of accurately controlling the puncturing position and depth, painless puncture and the like, can be used for transdermal drug delivery of chemical drugs, proteins, vaccines and the like, and has great development prospect. Microneedle technology has been widely used not only in the biomedical field but also in the cosmetic field, and has been widely used in europe, the united states of america, japan, korea, and the like. The micro-needle has wide application in the field of beauty, can be used for body shaping and skin beautifying, and has good effects of treating alopecia, repairing bubble marks and the like; in general, the application of microneedles in the aspect of beauty and body can be summarized as the following aspects: resisting skin aging, preventing and treating alopecia, reducing body weight, treating acne, removing dead skin tissue, reducing local accumulation of fat, and relieving dry skin.
However, most of the cosmetic microneedles popular in recent years are non-biodegradable solid microneedles, such as microneedle rollers, microneedle cosmetic materials, nano microneedles, etc., which all bring some disadvantages to consumers, such as: first, high cost and price. Second, security. At present, metal microneedles or monocrystalline silicon microneedles appear in the market, but due to the characteristic of small microneedles, the microneedles are reduced in strength and easy to break in the skin, so that the lower layer of the skin is inflamed and damaged, and the metal materials cause obvious pain, or some microneedles are made of other materials and cause damage to the human body, so that pores are enlarged and pigmentation are caused by frequent use; if the microneedle roller is used in the medical institution, the tool has the chance of remaining blood of other people, which is easy to cause the spread of AIDS, hepatitis and the like. Third, practicality. At present, most of cosmetic microneedle products can only be used under the guidance of professionals or professionals in a cosmetic institution or a hospital, or the use safety cannot be guaranteed due to technical reasons, so that the microneedles are difficult to operate and low in convenience.
The appearance of the soluble micro-needle just makes up the defects of the prior micro-needle in beautifying, and the hyaluronic acid micro-needle is one of the micro-needles. The microneedle takes the hyaluronic acid as the substrate to prepare the microneedle, and after the microneedle penetrates into the skin of a human body, the hyaluronic acid is dissolved and retained in the skin under the action of body fluid, so that the microneedle not only has a beautifying effect, but also does not cause inflammatory reaction because the hyaluronic acid is an endogenous substance of the human body. However, some soluble microneedles prepared from cosmetic active ingredients and hyaluronic acid have poor mechanical strength and are not enough to effectively puncture the stratum corneum to generate drug transport micro-channels, so that the improvement of the mechanical strength of the soluble microneedles is still a big problem in the process of developing microneedle preparations at present.
Disclosure of Invention
Based on the structure, the invention provides the soluble microneedle patch for whitening, and the soluble microneedle patch has good hardness and mechanical strength, can effectively puncture the stratum corneum to generate drug transport micro-channels, and transmits whitening active ingredients to the subcutaneous part, so that the soluble microneedle patch has a remarkable whitening effect.
The specific technical scheme is as follows:
the soluble microneedle patch for whitening comprises a needle tip and a substrate, wherein the needle tip is prepared from the following raw materials in parts by weight:
1 part of arbutin
15-30 parts of hyaluronic acid or salt thereof
5-25 parts of a shaping material;
the hyaluronic acid or the salt thereof is hyaluronic acid or sodium hyaluronate;
the excipient material is at least one of fructose, mannose, sodium carboxymethylcellulose and hypromellose; the substrate is prepared from a water-soluble high polymer material.
In some embodiments, the needle tip is prepared from the following raw materials in parts by weight:
1 part of arbutin
Hyaluronic acid or its salt 20-24 parts
8-22 parts of shaping material.
In some embodiments, the needle tip is prepared from the following raw materials in parts by weight:
1 part of arbutin
Hyaluronic acid or its salt 21-23 parts
14-19 parts of a shaping material.
In some embodiments, the needle tip is prepared from the following raw materials in parts by weight:
1 part of arbutin
Hyaluronic acid or its salt 21-23 parts
17.5 to 18.5 portions of shaping material.
In some of these embodiments, the excipient material is selected from at least two of fructose, mannose, sodium carboxymethyl cellulose, and hypromellose.
In some embodiments, the excipient material is composed of component a and component B, wherein component a is fructose and/or mannose, and component B is sodium carboxymethylcellulose and/or hypromellose.
In some of these embodiments, the mass ratio of component a to component B is 3-9: 1.
In some of these embodiments, the excipient material consists of fructose and sodium carboxymethyl cellulose in a mass ratio of 4-9: 1.
In some of these embodiments, the excipient material consists of fructose and sodium carboxymethyl cellulose in a mass ratio of 6-9: 1.
In some of these embodiments, the excipient material consists of fructose and sodium carboxymethyl cellulose in a mass ratio of 7.5-8.5: 1.
In some of these embodiments, the hyaluronic acid or salt thereof has a molecular weight of 1500kDa to 2500 kDa.
In some of the embodiments, the water-soluble polymer material is selected from at least one of polyvinyl alcohol and derivatives thereof, polyvinylpyrrolidone and derivatives thereof, hyaluronic acid or salts thereof, lactose, sorbitol, dextran, trehalose, and sucrose.
In some of these embodiments, the water-soluble polymeric material is hyaluronic acid or a salt thereof.
The invention also provides a preparation method of the soluble microneedle patch for whitening.
The specific technical scheme is as follows:
the preparation method of the soluble microneedle patch for whitening comprises the following steps:
dissolving the excipient material in water, adding the hyaluronic acid or the salt thereof, uniformly stirring, adding the arbutin, uniformly stirring, and removing bubbles to obtain a needle tip liquid; dissolving the water-soluble polymer material in water to obtain a base solution; injecting the needle point liquid into a microneedle mould, centrifuging, flatly paving the substrate liquid on the needle point liquid, centrifuging, drying and dewatering to obtain the needle.
In some embodiments, the total concentration of the raw materials in the needle tip liquid is 24-35wt%, and the raw materials refer to arbutin, excipient material and hyaluronic acid or salt thereof.
In some embodiments, the concentration of the water-soluble polymer material in the base solution is 2-4 wt%.
In some embodiments, the rotation speed of the centrifugation is 2000-3000rpm, the temperature is 0-8 ℃, and the centrifugation time is 1-3 min.
Arbutin is a natural active substance derived from green plants, and can effectively inhibit the activity of tyrosinase in skin melanocytes and block the formation of melanin, thereby reducing skin pigmentation, removing stains and freckles, and having low toxicity to melanocytes. However, the inventors of the present invention found through intensive studies that the skin permeability of arbutin is low due to strong hydrophilicity, skin stratum corneum obstruction, and the like, arbutin active ingredients cannot be effectively delivered to the subcutaneous skin, the due whitening effect of arbutin cannot be fully exerted, and the whitening effect is not significant. The invention further screens and obtains the specific type of excipient material from a large amount of high molecular materials through further research, and mixes arbutin, hyaluronic acid and the specific type and dosage of excipient material to prepare the soluble microneedle patch with good mechanical strength, so that the advantages of small size, high strength, accurate control of penetration position and depth, painless puncture and the like of the soluble microneedle can be effectively utilized, the barrier effect of skin cuticle can be broken, the skin permeation quantity of arbutin can be obviously improved, the whitening active factor arbutin is directly transmitted to the subcutaneous part, the defect that the traditional mode cannot exert the advantages of arbutin is avoided, and the whitening effect of arbutin is exerted to the maximum extent.
The soluble microneedle patch for whitening and the preparation method thereof have the following advantages and beneficial effects:
the soluble microneedle patch for whitening, which is prepared by mixing arbutin, hyaluronic acid or salt thereof and specific types and dosage of excipient materials, has good mechanical strength and enough hardness, is beneficial to piercing the skin, is not easy to break, can effectively pierce the stratum corneum of the skin to generate a drug transport micro-channel, and transmits whitening active factor arbutin to the subcutaneous part; meanwhile, the micro needle body has good solubility, can be quickly dissolved in the skin and quickly absorbed by the human body, and has the advantages of good biocompatibility and safety. The soluble microneedle patch for whitening avoids the defect that the advantages of arbutin cannot be exerted in the traditional skin care mode, and has remarkable effects of fading color spots and whitening skin.
The soluble microneedle patch for whitening prepared by the formula has proper viscosity in the preparation process, and is beneficial to microneedle forming.
Detailed Description
The dissolvable microneedle patch for whitening and the method for manufacturing the same according to the present invention will be described in further detail with reference to specific examples.
Example 1
The soluble microneedle patches for whitening prepared by different formulas are shown in table 1:
table 1 raw material formulation of soluble microneedle patch
Figure BDA0001354905620000051
Note: HA refers to hyaluronic acid, which HAs a molecular weight of 2000 kDa.
The preparation method comprises the following steps:
weighing appropriate amount of the raw materials shown in Table 1 and their mixture ratio, placing in 10ml centrifuge tube, taking purified water 2.5 times of the total mass of the raw materials as solvent, vortex, mixing uniformly, dissolving, and preparing 8 kinds of needle tip solutions according to the prescription in Table 1. Sucking the needle point liquid by a syringe, injecting 500 mu l of the needle point liquid into a microneedle mould, paving, centrifuging at 3000rpm in a refrigerated centrifuge (the temperature is 4 ℃) for 2min, sucking the redundant needle point liquid, sucking 1000 mu l of a base liquid (sodium hyaluronate (molecular weight 200kDa): water 1:30 (mass ratio)) by the syringe, flatly paving on the needle point liquid, centrifuging at 2000rpm in the refrigerated centrifuge (the temperature is 4 ℃) for 2min, taking out, drying in a normal-temperature drying device for 24 hours, taking out, stripping the mould, and obtaining 8 soluble microneedle patches for whitening prepared by the 8 prescription raw materials.
Example 2
The 8 kinds of dissolvable microneedle patches for whitening prepared in example 1 were tested for hardness and extensibility.
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 2. 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 2 test parameters
Figure BDA0001354905620000061
After the test is finished, the tested microneedle sample on the carrying platform is taken out, and the local morphological change of the microneedle is observed by using a microscope after the acting force of the probe of the texture analyzer is observed.
The results of testing the hardness and ductility of microneedles prepared according to different formulations using a texture analyzer are shown in table 3.
TABLE 3 hardness and ductility of microneedles of different formulations
Figure BDA0001354905620000062
Figure BDA0001354905620000071
The capability of the needle point of the soluble microneedle that the needle point bears acting force without breaking in the process of being pressed down by the texture analyzer probe can be used as the strength of the microneedle, the higher the strength is, the larger the pressure borne by the microneedle is, and the pressure is used as a parameter for representing the hardness of the microneedle. When the micro-needle is pressed down, the micro-needle body generates elastic deformation and plastic deformation under the action of external force, the deformation of the micro-needle body and the deformation of the micro-needle body can represent the characteristic that the micro-needle can deform without breaking under the action of the external force, and the ductility of the micro-needle is measured through a texture instrument, which represents the plastic deformation capacity of the micro-needle body before the micro-needle body breaks under the action of the force. Therefore, in the practical application process, the mechanical properties of the microneedles represented by the strength and the extensibility of the microneedles are characterized in that the stronger the microneedle is, the larger the force for breaking is, the better the extensibility is, the microneedle is not easy to break, and the mechanical properties are higher.
The experimental results show that the hardness is in order: f7> F1> F4> F2> F3> F8> F6> F5, the ductility being in the order: f5> F2> F1> F3> F7> F6> F8> F4.
Comparing F1-F3, only changing the content of fructose, and in terms of hardness effect, along with the decrease of the content of fructose, the hardness of the prepared microneedle sample is also decreased, which shows that the addition of the fructose is beneficial to improving the hardness of the microneedle sample; for ductility, when prescribed HA: fructose: sodium carboxymethylcellulose: when the ratio of arbutin to arbutin is 22:12:2:1, the prepared microneedle sample has optimal ductility and higher hardness, namely, the optimal synergistic effect and optimal strength are achieved in the ratio.
In comparison among F1, F4 and F5, the difference among the three is that whether the polymer auxiliary material sodium carboxymethyl cellulose is added or not, the hardness and ductility results can be obtained, and the ductility of the prepared microneedle sample tends to increase along with the increase of the proportion of the sodium carboxymethyl cellulose in the prescription in the ductility, which indicates that the addition of the sodium carboxymethyl cellulose is beneficial to the improvement of the ductility of the microneedle sample; in contrast, when the prescription HAs HA: fructose: sodium carboxymethylcellulose: when the ratio of arbutin to arbutin is 22:16:2:1, the prepared microneedle sample has the optimal hardness and the good ductility, namely, the optimal synergistic effect is achieved under the ratio.
In comparison between F1 and F6, the difference between the fructose and mannose is found in hardness and ductility, and F1 containing fructose is superior to F6 containing mannose in molecular structure and property.
In comparison of F1 with F7, F7 containing hypromellose is comparable in hardness to F1 containing sodium carboxymethylcellulose, but inferior in ductility to F1.
No excipient is added in the prescription F8, so that the prepared microneedle sample is far inferior to other prescriptions in hardness and ductility, and cannot meet the requirement of effectively penetrating the skin.
In conclusion, the hardness and ductility of the soluble microneedles prepared from F1 and F2 are better than those of the soluble microneedles prepared from other formulas.
Example 3 solubility assay of soluble microneedle patches
Accurately weighing gelatin, purified water and sucrose with different masses according to the proportion shown in Table 4, placing in a 50ml centrifuge tube, dissolving overnight in a water bath kettle at 90 ℃, centrifuging, degassing, quickly transferring to a transparent culture dish, cooling, and solidifying to obtain gelatin and sucrose gel with different water contents.
TABLE 4 composition of gelatin gel composition
Figure BDA0001354905620000081
The 8 soluble microneedle patches prepared in example 1 are inserted into the surface of a gel body along the edge of a culture dish, observed from the side by an electron microscope at different time points, the dissolution conditions of the soluble microneedles at different time points are recorded, no obvious visible microneedle body is observed as a dissolution end point, the microneedles are taken out and further observed under the microscope to confirm the dissolution time points, the solubility of the soluble microneedles in gelatin with different water contents is shown in table 5, and due to the physiological structure of the skin, the layering level of the skin takes the stratum corneum as the outermost layer, the water content is about 20% at the lowest, a transparent layer, a granular layer, a spinous cell layer and a basal layer are sequentially arranged inwards, the proportion of each layer in the surface layer of the skin is different, and the higher the water content of the inner part is about 70% of human tissue, so that the proportion of the different layers is listed as the stratum corneum: transparent layer: granular layer: basal layer: 2:1.5:2.5:3:1, and the sum of the different dissolution times of the percentages of different layers is stated as total dissolution time + 30 × t30 × + 3632%, and the total dissolution time in vivo is evaluated as 30 × t + 3615% + 3632%.
TABLE 5 solubility of soluble microneedles of different formulations inserted into gelatin
Figure BDA0001354905620000091
F8, F2, F3, F7, F4, F6, F1 and F5, and the in vitro comprehensive dissolution time of the formulas F1, F4-F6 and F7 is controlled to be about 40min through comparison, and the dissolution is relatively quick compared with other formulas. The composition of the prescription shows that the comprehensive in-vitro dissolution time varies between F1 and F3 along with the change of the proportion of fructose in the prescription, wherein the in-vitro dissolution time of F2 is closer to that of F3, and the in-vitro dissolution time of F1 is better than that of the former two. This is due to the large difference in the ability to absorb water within the gelatin as different proportions of fructose and other materials interact with each other upon dissolution. In addition, in comparison of F1, F4 and F5, it was found that as the proportion of sodium carboxymethylcellulose in the formulation increased, the in vitro dissolution time of the microneedles decreased gradually, which was associated with the strong water absorption capacity of sodium carboxymethylcellulose in gelatin, more sodium carboxymethylcellulose accounted for faster water absorption capacity of the formulation in gelatin leading to faster in vitro dissolution times, but overall, the differences were not great. In comparison among F1, F6 and F7, the use of mannose and hypromellose for F6 and F7, respectively, resulted in a slight increase in the in vitro dissolution time of F6 and F7 compared to F1, which is mainly due to the difference in water absorption capacity of different substances in gelatin. And F8 is the microneedle sample without the addition of the shaping material, and the result shows that the comprehensive dissolution time is obviously prolonged compared with other parts, so that the addition of the shaping material has obvious influence on the in-vitro dissolution time of the microneedle sample, and the addition of the shaping material can obviously improve the solubility of the microneedle.
Combining the hardness and ductility results of example 2, the F1 microneedles had good hardness and mechanical strength and solubility, and were best used as whitening dissolvable microneedles.
Example 4 soluble microneedle patch whitening effect investigation
The soluble microneedle patch for whitening prepared in formulation 1 of example 1 was tested for whitening skin care effects.
The test method comprises the following steps: subjects were 48, 25-45 years old, with color spots on their faces. The microneedle patch was pressed into the pigmented spot on the face of the subject, removed after 4 hours, and used twice a week.
And (3) testing results: 48 people have obvious whitening and freckle removing effects after the use for one week, the facial freckles of 48 people are obviously improved and lightened after the use for 4 weeks, and the facial freckles of 43 people basically disappear after the use for 8 weeks.
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 soluble microneedle patch for whitening is characterized by comprising a needle point and a substrate, wherein the needle point is prepared from the following raw materials in parts by weight:
1 part of arbutin
15-30 parts of hyaluronic acid or salt thereof
5-25 parts of a shaping material;
the hyaluronic acid or the salt thereof is hyaluronic acid or sodium hyaluronate, and the molecular weight is 1500kDa-2500 kDa;
the excipient material consists of fructose and sodium carboxymethyl cellulose in a mass ratio of 6-9:1, or consists of fructose and hydroxypropyl methylcellulose in a mass ratio of 8: 1; the substrate is prepared from a water-soluble high polymer material.
2. The dissolvable microneedle patch for whitening according to claim 1, wherein the needle tip is prepared from the following raw materials in parts by weight:
1 part of arbutin
Hyaluronic acid or its salt 20-24 parts
8-22 parts of shaping material.
3. The dissolvable microneedle patch for whitening according to claim 1, wherein said excipient material consists of fructose and sodium carboxymethyl cellulose in a mass ratio of 8: 1.
4. The dissolvable microneedle patch for whitening according to claim 3, wherein said needle tip is composed of hyaluronic acid or sodium hyaluronate, fructose, sodium carboxymethylcellulose, and arbutin in a weight ratio of 22:16:2: 1.
5. The soluble microneedle patch for whitening according to claim 1, wherein the needle tip is composed of hyaluronic acid or sodium hyaluronate, fructose, hypromellose and arbutin in a weight ratio of 22:16:2: 1.
6. The dissolvable microneedle patch for whitening according to any one of claims 1-5, wherein the molecular weight of said hyaluronic acid or its salt is 2000 kDa.
7. The dissolvable microneedle patch for whitening according to any one of claims 1 to 5, wherein said water-soluble high molecular material is selected from at least one of polyvinyl alcohol and its derivatives, polyvinylpyrrolidone and its derivatives, hyaluronic acid or its salts, lactose, sorbitol, dextran, trehalose, and sucrose.
8. The dissolvable microneedle patch for whitening according to claim 7, wherein said water-soluble high molecular material is hyaluronic acid or a salt thereof.
9. A method of manufacturing the dissolvable microneedle patch for whitening according to any one of claims 1 to 8, comprising the steps of: dissolving the excipient material in water, adding the hyaluronic acid or the salt thereof, uniformly stirring, adding the arbutin, uniformly stirring, and removing bubbles to obtain a needle tip liquid; dissolving the water-soluble polymer material in water to obtain a base solution; injecting the needle point liquid into a microneedle mould, centrifuging, flatly paving the substrate liquid on the needle point liquid, centrifuging, drying and dewatering to obtain the needle.
10. The method of preparing the dissolvable microneedle patch for whitening according to claim 9, wherein the total concentration of the raw materials in the needle point liquid is 24-35wt%, the raw materials refer to the arbutin, excipient material and hyaluronic acid or salt thereof; and/or the concentration of the water-soluble polymer material in the base solution is 2-4 wt%.
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