CN108969880B - Soluble microneedle film and preparation method thereof - Google Patents
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- 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
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- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
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- 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
- A61M2037/0023—Drug applicators using microneedles
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- 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
- A61M2037/0046—Solid 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
- A61M2037/0053—Methods for producing microneedles
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Abstract
The invention discloses a soluble microneedle film and a preparation method thereof, wherein the preparation method comprises the following operation steps: A1) preparing a microneedle mould; A2) preparing a premixed solution; A3) forming a microneedle film; A4) demolding, packaging and sterilizing. The soluble microneedle film is prepared by mixing sodium hyaluronate, water-soluble chitosan and other functional components in proportion according to the method provided by the invention. The invention adopts the groove structure die processed by laser micromachining for production, has simple and convenient production process and is suitable for large-scale production; the soluble microneedle film provided by the invention has the film strength capable of meeting the use requirement and has the functions of moisturizing, promoting repair, resisting bacteria, whitening and resisting aging.
Description
Technical Field
The invention relates to the field of beauty treatment and skin drug delivery, in particular to a soluble microneedle film and a preparation method thereof.
Background
Microneedle technology is currently widely used in the cosmetic and dermal drug delivery fields. The micro-needle is a micron-scale array structure which is made of metal, silicon, polymer and other materials, has the length of 25-2000 mu m and has a needle point in a symmetrical conical shape or an asymmetrical inclined plane shape. The soluble microneedle is generally prepared from a high molecular material which can be dissolved or degraded biologically, and the bioactive substances coated in the soluble microneedle are gradually released along with the dissolution of the soluble material in the skin to play a role. Soluble microneedles have better biocompatibility and larger drug loading than insoluble microneedles, and are receiving more and more attention and research. The soluble microneedle film has been widely used in europe, the united states, the japanese and the korean, and the like, and has significant effects in the aspects of resisting skin aging, fading wrinkles, repairing fiber elasticity, treating acne, removing dead skin, and the like.
The ideal soluble cosmetic microneedle film should have the following characteristics: 1) safety, no infection; 2) the effects of resisting aging, whitening and the like can be achieved; 3) practicability, the material strength meets the requirements; 4) cost performance, simple and convenient production process of the microneedle film and suitability for large-scale production.
At present, materials for preparing the soluble microneedle membrane mainly come from sodium hyaluronate, and other components are added according to needs to enhance the beautifying effect, for example, components such as collagen, polysaccharide substances and glycerin are added to enhance the strength, the moisture retention property, the repair promotion property, the whitening property and the like of the microneedle membrane.
Sodium hyaluronate, also called hyaluronic acid, is a polysaccharide substance widely present in connective tissues, mucus tissues, crystalline lens of eyeball and some bacterial tunica, plays an important role in human dermal layer of skin, and plays an important role in maintaining skin elasticity. With the age, the loss speed of the sodium hyaluronate in the skin is higher than the growth speed, so that the skin gradually loses luster and elasticity, and the aging phenomena such as wrinkles and the like occur. Research shows that the exogenously supplemented sodium hyaluronate also has the function of keeping the skin elasticity of the original sodium hyaluronate of the body and has the function of slowing down the aging. And is an effective mode for exogenously supplementing sodium hyaluronate by the microneedle technology.
When the microneedle which is prepared by taking the sodium hyaluronate as the main matrix material is penetrated into the skin of a human body, the sodium hyaluronate is dissolved and retained in the skin under the action of liquid, so that the beautifying effect is achieved. The high molecular sodium hyaluronate has strong hydrophilicity, can absorb 1000 times of water by volume, can quickly fill and level fine wrinkles of skin after water absorption and expansion, but the solution viscosity is sharply increased along with the increase of concentration, which is not beneficial to the production of a microneedle injection molding method; the low-molecular sodium hyaluronate can stimulate the production of collagen in the skin and increase the elasticity and plumpness of the skin, but the mechanical strength of the needle body is not enough to penetrate the skin. It can be seen that the production and performance requirements of microneedles can not be met simultaneously with only a single molecular weight of sodium hyaluronate.
The preparation process of the soluble microneedle is mainly obtained by injecting functional liquid into a microneedle mould, and then drying, stripping and cutting. The microneedle mould is a key factor of microneedle production cost and production operation simplicity. At present, a domestic microneedle mould is generally obtained by firstly preparing solid male mould microneedles by micro-electro-mechanical processing or chemical etching, then obtaining a female mould through PDMS (polydimethylsiloxane) composite mould, filling a premixed solution into the female mould, and drying. In the process, the process of the female mold is complicated through the male mold replication, inconvenience is brought to the subsequent production and processing of the prepared microneedle, the preparation methods are complicated and expensive, the cost of the microneedle product is increased, and the selling price of a consumer is always high and cannot be reduced.
In recent years, intensive research on the preparation of microneedle products has been conducted in China: the Chinese patent with publication number CN103893018A relates to sodium hyaluronate microneedle, because of adding hyperbranched polysulfone amine or polyester, the mechanical property is reduced, and the microneedle is not easy to demould in the preparation process and has poor microneedle forming. The Chinese patent with the publication number of CN102178616B, discloses a hyaluronic acid micro-needle adhesive film and a preparation method thereof, wherein the hyaluronic acid micro-needle adhesive film is composed of hyaluronic acid, collagen, polyhydric alcohol, functional active ingredients and the like, but the patent does not relate to the molecular weight of hyaluronic acid, so that the injection molding is difficult in the production process. The Chinese patent CN101687090B mentions hyaluronic acid micro-needles, but the micro-needles prepared by the patent contain 50 to 70 percent of collagen besides hyaluronic acid. It is reported in the literature that a microneedle patch containing collagen causes an inflammatory reaction after penetrating into the skin, and sodium hyaluronate with a molecular weight of 40 ten thousand or more is preferred in the patent, and is not favorable for casting into a film or injecting into the micropores of a microneedle mold. The Chinese patent CN 104027324A mentions that the microneedle is prepared from chitosan, collagen and sodium hyaluronate, but the preparation method provided by the patent is complex in process and is not suitable for industrial production. Chitosan and sodium hyaluronate are added into the composition of the microneedle film described in chinese patents CN105078880A and CN201610913515, but there is no clear limitation on what specification of sodium hyaluronate is, and the function of hyaluronic acid cannot be described. Chinese patent CN107184417A also mentions that two kinds of sodium hyaluronate with molecular weight are shared, but antibacterial property is not considered, and in addition, the patent needs to prepare and pour a needle point liquid and a base liquid respectively, so that the process is complicated, and the industrial production is not facilitated.
In summary, no process capable of completely considering safety, practicability, whitening anti-aging effect and optimizing a production route exists in the preparation process of the water-soluble microneedle at present.
Disclosure of Invention
The invention aims to provide a preparation method of a soluble microneedle membrane, which uses a groove structure die for laser micromachining to carry out production, has simple and convenient operation in the production process and is suitable for large-scale production; the mould can be used repeatedly, and is favorable for reducing the cost. The strength of the material of the soluble microneedle film prepared by the method can meet the use requirement.
The invention also provides a soluble microneedle membrane, in particular to a soluble microneedle membrane which is prepared by forming a novel formula by modern recognized sodium hyaluronate with moisturizing and repairing promoting functions and water-soluble chitosan with moisturizing, repairing promoting and antibacterial functions, and adding other functional components such as one or more of glycerol, pentanediol, hexanediol, water-soluble collagen, epidermal growth factor, vitamin C, rice bran stock solution or arbutin and the like.
The invention provides a preparation method of a soluble microneedle film, which comprises the following operation steps:
A1) preparing a microneedle mould, namely performing laser micromachining on a special groove structure mould by adopting a laser micromachining system to obtain the microneedle mould, wherein the mould can be repeatedly used;
A2) preparation of the premix solution: mixing one or more of large molecular weight sodium hyaluronate, small molecular weight sodium hyaluronate and water soluble chitosan with purified water, stirring and dissolving; adding other functional substances such as one or more of glycerol, pentanediol, hexanediol, water-soluble collagen, epidermal growth factor, vitamin C, rice bran stock solution or arbutin into the system after completely dissolving, mixing uniformly, and vacuumizing to remove bubbles to obtain a premixed solution;
A3) casting and molding of the microneedle film: the premixed solution is poured into a special microneedle mould at one time, vacuumized and dried in an oven;
A4) demolding, packaging and sterilizing: stripping and demolding to obtain the soluble microneedle film, cutting, packaging, and finally performing irradiation sterilization.
The invention also optimizes the mould for preparing the soluble microneedle film further: the mold adopts a laser micromachining system of purple light with the wavelength of 355nm to carry out laser micromachining on a molded groove structure mold under certain parameters, and the length of a microneedle, the conicity and the smoothness of the internal form are adjusted by adjusting the laser power and the machining speed, so that the mold for preparing the soluble microneedle film is obtained, and the soluble microneedle film mold is further optimized.
Preferably, the formed groove structure mold comprises a crescent shape, a rectangle shape, a square shape, a diamond shape, a circular shape or an oval shape, the height of the groove is 5-50 mm, and the horizontal deviation of the inner surface of the groove is 1-100 mu m;
preferably, the distance between the side plate (1) of the microneedle mould and the microneedle array (2) is 5-50 mm, the height of the microneedle mould is 10-100 mm, and the width of the microneedle mould is 50-1000 mm;
preferably, the microneedle mould is made of stainless steel, polytetrafluoroethylene, silica gel and PDMS.
The invention also provides a soluble microneedle film which mainly comprises sodium hyaluronate, water-soluble chitosan and other functional components;
the sodium hyaluronate is one or two of sodium hyaluronate with a large molecular weight of 500-2000 kDa and a small molecular weight of 10-100 kDa;
the water-soluble chitosan is one or more of carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate, chitosan sulfate, chitosan oligosaccharide and hyaluronic acid-like chitosan;
the other functional components are one or more of glycerol, pentanediol, hexanediol, water-soluble collagen, epidermal growth factor, vitamin C, rice bran stock solution or arbutin.
The weight contents of the large molecular weight sodium hyaluronate, the small molecular weight sodium hyaluronate, the water-soluble chitosan and other functional components of the soluble microneedle film are respectively 0-3%: 0-15%: 0-3%: 0-2%, the rest is the content of purified water.
The microneedle component is prepared into the soluble microneedle membrane according to the preparation method of the soluble microneedle membrane, and the soluble microneedle membrane has the following characteristics:
preferably, the microneedles are conical, triangular pyramidal, quadrangular pyramidal, hexagonal pyramidal, crescent-shaped;
preferably, the length of the microneedle is 10 to 3000 μm;
preferably, the diameter of the bottom of the microneedle is 50-1000 μm;
preferably, the distance between the micro-needles is 50 to 3000 mu m.
Under the specification condition defined by the invention, the obtained soluble microneedle film can timely, quickly and effectively input the functional components into the target action part, has the functions of moisturizing, promoting repair, resisting bacteria, whitening and resisting aging, and has higher safety and no infection.
In conclusion, the invention has the beneficial effects that:
1. the preparation method of the soluble microneedle membrane provided by the invention is characterized in that a solution containing different components with beauty treatment effects is poured on a mould with a groove structure obtained by laser micromachining, and the microneedle membrane is prepared by pouring, molding, demolding, packaging and sterilizing, and the method is simple and convenient to operate and is suitable for large-scale production; the die with the groove structure obtained by laser micromachining can be repeatedly used, so that the production cost is favorably reduced; the strength of the material of the soluble microneedle film prepared by the method can meet the use requirement.
2. The mold for preparing the soluble microneedle membrane can be prepared by a laser micromachining system, and the length of the microneedle and the taper and smoothness of the internal form are adjusted by adjusting the laser power and the machining speed, so that the process steps can be greatly simplified, the cost is further reduced, the industrial production is facilitated, and the mold has strong practicability.
3. The height of the groove of the microneedle mould is 5-50 mm, and the microneedle mould can be used for loading a solution for preparing a microneedle film and is beneficial to primary perfusion; the horizontal deviation of the inner surface of the groove is 1-100 mu m, which is beneficial to the flatness and the uniform thickness of the prepared microneedle film; the distance between the side plate (1) of the microneedle mould and the microneedle array (2) is 5-50 mm, so that the microneedle film can be peeled off conveniently after being dried. The microneedle film prepared by using the microneedle mould is simple and convenient to operate and suitable for large-scale production.
4. According to the invention, the defect of insufficient mechanical strength of the micro-needle film obtained by the sodium hyaluronate with small molecular weight is overcome by changing the concentration and components of the micro-needle premixed solution; the sodium hyaluronate with high molecular weight has the problem that a microneedle film with a uniform structure cannot be obtained due to high viscosity and poor flowability, so that the soluble microneedle film with high strength and toughness can be prepared.
5. The sodium hyaluronate with small molecular weight used in the invention has the functions of moisturizing, repair promotion, anti-inflammation and bacteriostasis, and the water-soluble chitosan also has the functions of moisturizing, repair promotion and antibiosis, and the two have synergistic effect, so that the beautifying effect is better.
6. The glycerin, the pentanediol and the hexanediol which are other functional components in the microneedle film have a better moisturizing effect; the water-soluble collagen and the epidermal growth factor have good anti-aging effect, and simultaneously have good whitening effect in vitamin C, rice bran stock solution and arbutin.
7. The needle body of the microneedle membrane has enough mechanical strength, can successfully penetrate into the stratum corneum of the skin, can effectively input functional components of the microneedle membrane into a target action part, has quick response, and can play obvious effects of moisturizing, promoting repair, resisting bacteria, whitening and resisting aging.
Drawings
Fig. 1 is a view showing a structure of a microneedle mold.
Fig. 2 a microneedle film sample prepared.
Figure 3 microneedle micrographic image.
Detailed Description
The present invention is further illustrated by the following examples, which are set forth merely for the purpose of illustration and are not to be construed as limiting the scope of the invention.
Example 1:
the soluble microneedle film disclosed by the embodiment has the main functions of moisturizing, repairing promotion and antibiosis, and is prepared by the following specific steps:
1. preparing a microneedle mould, namely performing laser micromachining on a specially-made stainless steel mould containing a groove structure by adopting a laser micromachining system of purple light with the wavelength of 355nm, wherein the obtained microneedle point of the microneedle mould is in a conical shape, the length of the needlepoint is 100 mu m, the bottom diameter of the needlepoint is 600 mu m, the distance between the needlepoints is 300 mu m, and the average number of the microneedle points per square centimeter is about 300;
2. preparation of the premix solution: mixing 1g of large molecular weight sodium hyaluronate, 8g of small molecular weight sodium hyaluronate, 1g of carboxymethyl chitosan and 89g of purified water, and stirring for dissolving; after complete dissolution, adding 1g of glycerol into the system, uniformly mixing, vacuumizing and removing bubbles to obtain a premixed solution;
3. casting and molding of the microneedle film: filling the premixed solution into a special microneedle mould at one time, vacuumizing, drying and drying;
4. demolding, packaging and sterilizing: stripping and demolding to obtain the soluble microneedle film, cutting, packaging, and finally performing irradiation sterilization.
Example 2:
the soluble microneedle film disclosed by the embodiment has the main functions of resisting aging, moisturizing, promoting repair and resisting bacteria, and is prepared by the following specific steps:
1. preparing a microneedle mould, namely performing laser micromachining on a special polytetrafluoroethylene mould containing a groove structure by adopting a laser micromachining system of ultraviolet light with the wavelength of 355nm, wherein the obtained microneedle point of the microneedle mould is in a conical shape, the length of the needlepoint is 150 mu m, the bottom diameter of the needlepoint is 500 mu m, the distance between the needlepoints is 600 mu m, and the average number of the microneedle points per square centimeter is about 144;
2. preparation of the premix solution: mixing 2g of large molecular weight sodium hyaluronate, 10g of small molecular weight sodium hyaluronate, 1g of chitosan hydrochloride and 86.4g of purified water, and stirring for dissolving; after the dissolution is completed, 0.6g of water-soluble collagen is added into the system, and the mixture is uniformly mixed and vacuumized to remove air bubbles, so that a premixed solution is obtained;
3. casting and molding of the microneedle film: filling the premixed solution into a special microneedle mould at one time, vacuumizing, drying and drying;
4. demolding, packaging and sterilizing: stripping and demolding to obtain the soluble microneedle film, cutting, packaging, and finally performing irradiation sterilization.
Example 3:
the soluble microneedle film disclosed by the embodiment has the main functions of whitening, moisturizing, repairing promotion and antibiosis, and is prepared by the following specific steps:
1. preparing a microneedle mould, namely performing laser micromachining on a specially-made PDMS mould containing a groove structure by adopting a laser micromachining system of purple light with the wavelength of 355nm, wherein the obtained microneedle point of the microneedle mould is in a conical shape, the length of the needlepoint is 200 mu m, the bottom diameter of the needlepoint is 600 mu m, the distance between the needlepoints is 700 mu m, and the number of the average microneedle points per square centimeter is about 100;
2. preparation of the premix solution: mixing 1g of large molecular weight sodium hyaluronate, 10g of small molecular weight sodium hyaluronate, 3g of chitosan hydrochloride and 85.0g of purified water, and stirring for dissolving; after the rice bran stock solution is completely dissolved, 0.8g of rice bran stock solution and 0.2g of arbutin are added into the system, mixed evenly and vacuumized to remove air bubbles, thus obtaining a premixed solution;
3. casting and molding of the microneedle film: filling the premixed solution into a special microneedle mould at one time, vacuumizing, drying and drying;
4. demolding, packaging and sterilizing: stripping and demolding to obtain the soluble microneedle film, cutting, packaging, and finally performing irradiation sterilization.
Example 4:
4.1 morphology Observation and hardness detection of the film
The prepared microneedle film is placed under a 40-time optical microscope, and the shape of the microneedle is observed, which is shown in table 1; and the intensity of the microneedles in different embodiments is detected by a texture analyzer, and the results are shown in table 1.
Cytotoxicity assays
Cytotoxicity test was carried out according to the method prescribed in GB/T16886.5-2003 (direct contact method), and is shown in Table 1.
TABLE 1 EXAMPLES 1-3 morphology and Performance test
4.3 bacteriostatic test
Firstly, preparing a mixed bacteria culture medium plate, and respectively picking a small amount of cultured staphylococcus aureus, pseudomonas aeruginosa and escherichia coli slant culture medium substances in 5ml of sterile normal saline by using an inoculating loop to prepare bacterial suspension. Adding 1.0ml of the bacterial suspension into a sterilized and dried culture dish, adding a common nutrient broth agar culture medium cooled to about 50 ℃, shaking up, and fully condensing for later use. And then carrying out an antibacterial test, cutting the sample membrane into a round piece of 1.0cm, pasting the round piece on a mixed bacteria culture medium plate, carrying out inverted culture at the temperature of 35-37 ℃ for 20-24 hours, and observing the growth condition of bacteria, wherein the growth condition is shown in table 2.
Table 2 examples 1-3 results of bacteriostatic experiments
4.4 anti-aging Effect of the microneedle film
The clinical protocol of the treatment group, which is a treatment group treated by the microneedle film of example 2 on one side of 10 volunteer subjects aged 45-60 years and having significant crow's feet (wrinkles cannot cross each other and major wrinkles are at least 2cm long), and the control group treated by the microneedle film on the other side of the volunteer subjects not treated, was not treated, and the crow's feet of the treatment group and the control group were measured two weeks later, and statistical analysis shows that the crow's feet of the treatment group are significantly shortened relative to the control group, the average length of the crow's feet of the control group is 2.6, the average length of the crow's feet of the control group is not increased, and the average length of the crow's feet of the treatment group is 1.7. The soluble microneedle disclosed by the invention has an anti-aging function of removing wrinkles of skin.
Micro needle film whitening effect
Skin color (skin grade classification: five grades of I, II, III, IV and V are divided according to skin from light to dark) of 36 volunteer skin is measured according to Lab chromaticity space specified by International society for illumination, the micro needle film is pressed on the face of the volunteer after the test is graded according to skin color, the micro needle film is removed after 4 hours, the micro needle film is used once a day, and the whitening effect is observed after two weeks: the skin of 36 subjects was found to have a certain whitening effect, and the specific results are shown in table 3.
Table 3 examples 1 to 3 whitening effect
It should be noted that: the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (1)
1. The preparation method of the soluble microneedle film is characterized by comprising the following operation steps:
A1) preparing a microneedle mould, namely performing laser micromachining on a prepared special mould without a microneedle array by adopting a laser micromachining system with 355nm violet light;
the distance between the side plate (1) of the microneedle mould and the microneedle array (2) is 5-50 mm, the height of the microneedle mould is 10-100 mm, and the width of the microneedle mould is 50-1000 mm;
the groove structure of the microneedle mould comprises a crescent shape, a square shape, a diamond shape, a round shape and an oval shape, the height of the groove is 5-50 mm, and the horizontal deviation of the inner surface of the groove is 1-100 mu m;
the microneedle mould is made of stainless steel materials, silica gel and PDMS;
A2) preparation of the premix solution: mixing sodium hyaluronate, water-soluble chitosan and water, stirring and dissolving; adding other functional components into the system after complete dissolution, uniformly mixing, vacuumizing and removing bubbles to obtain a premixed solution;
the sodium hyaluronate consists of water-soluble sodium hyaluronate with the large molecular weight of 500-2000 kDa and the small molecular weight of 10-100 kDa;
the water-soluble chitosan is one or more of carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate, chitosan sulfate, chitosan oligosaccharide and hyaluronic acid-like chitosan;
the other functional components are one or more of glycerol, water-soluble collagen, epidermal growth factor, vitamin C, rice bran stock solution and arbutin;
the weight contents of the high molecular weight water-soluble sodium hyaluronate, the low molecular weight water-soluble sodium hyaluronate, the water-soluble chitosan and other functional components are respectively 0-3%: 0-15%: 0-3%: 0.6-3%, the rest is water content;
A3) forming the microneedle film: pouring a mold, coating the premixed solution in a specially-made microneedle mold at one time, vacuumizing, and then continuously keeping the vacuum environment for drying;
A4) demolding, packaging and sterilizing: stripping and demolding to obtain the soluble microneedle film, cutting, packaging, and finally performing irradiation sterilization;
the needle point of the micro-needle film is one of a cone, a triangular cone, a quadrangular pyramid and a crescent;
the length of the needle tip of the microneedle is 10-3000 mu m;
the diameter of the bottom of the microneedle tip is 50-1000 mu m;
the distance between the needle points of the micro-needles is 50 to 3000 mu m.
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| TWI692499B (en) * | 2019-07-19 | 2020-05-01 | 怡定興科技股份有限公司 | Needle base composition for microneedle patch and microneedle patch containing same |
| CN110664646B (en) * | 2019-11-14 | 2022-04-29 | 广州新济薇娜生物科技有限公司 | Composition with whitening effect, high-drug-loading-rate whitening soluble microneedle patch and preparation method thereof |
| CN110917489A (en) * | 2019-12-27 | 2020-03-27 | 广东工业大学 | Antibacterial chitosan microneedle and application thereof |
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| CN111450405A (en) * | 2020-05-08 | 2020-07-28 | 无锡元旭生物技术有限公司 | Rapid preparation method of soluble microneedle patch stock solution |
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| CN114228054B (en) * | 2021-12-14 | 2022-08-16 | 优微（珠海）生物科技有限公司 | Microneedle mould and preparation method of microneedle patch |
| CN115400341B (en) * | 2022-08-30 | 2024-02-02 | 华中科技大学 | Soluble polymer microneedle and preparation method thereof |
| CN116548205B (en) * | 2023-04-24 | 2024-02-13 | 南京师范大学 | Microneedle preparation, microneedle patch, and preparation methods and applications thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7591806B2 (en) * | 2004-05-18 | 2009-09-22 | Bai Xu | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances |
| CN102917751A (en) * | 2010-05-28 | 2013-02-06 | 久光制药株式会社 | Device having array provided with fine protrusions |
| CN103893018A (en) * | 2014-04-16 | 2014-07-02 | 华熙福瑞达生物医药有限公司 | Soluble hyaluronic acid micro-needle patch |
| CN105078880A (en) * | 2015-09-12 | 2015-11-25 | 北京化工大学 | Macromolecular soluble microneedle used for cutaneous penetration of polypeptide and protein medicines and preparation method of macromolecular soluble microneedle |
| CN107158368A (en) * | 2017-05-11 | 2017-09-15 | 广州新济药业科技有限公司 | Epidemic meningitis polysaccharide conjugate vaccine solubility microneedle patch and preparation method thereof |
| CN107456649A (en) * | 2016-06-03 | 2017-12-12 | 赛诺凡生物科技有限公司 | The microneedle patch containing hyaluronic acid for beautifying use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120027837A1 (en) * | 2010-07-27 | 2012-02-02 | Massachusetts Institute Of Technology | Multilayer coating compositions, coated substrates and methods thereof |
| CN105434332A (en) * | 2015-12-02 | 2016-03-30 | 江汉大学 | Preparation method for water-soluble biological macromolecular microneedle membrane |
-
2018
- 2018-06-12 CN CN201810598273.9A patent/CN108969880B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7591806B2 (en) * | 2004-05-18 | 2009-09-22 | Bai Xu | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances |
| CN102917751A (en) * | 2010-05-28 | 2013-02-06 | 久光制药株式会社 | Device having array provided with fine protrusions |
| CN103893018A (en) * | 2014-04-16 | 2014-07-02 | 华熙福瑞达生物医药有限公司 | Soluble hyaluronic acid micro-needle patch |
| CN105078880A (en) * | 2015-09-12 | 2015-11-25 | 北京化工大学 | Macromolecular soluble microneedle used for cutaneous penetration of polypeptide and protein medicines and preparation method of macromolecular soluble microneedle |
| CN107456649A (en) * | 2016-06-03 | 2017-12-12 | 赛诺凡生物科技有限公司 | The microneedle patch containing hyaluronic acid for beautifying use |
| CN107158368A (en) * | 2017-05-11 | 2017-09-15 | 广州新济药业科技有限公司 | Epidemic meningitis polysaccharide conjugate vaccine solubility microneedle patch and preparation method thereof |
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