CN113274344A - Bubble type hollow microneedle and preparation method thereof - Google Patents
Bubble type hollow microneedle and preparation method thereof Download PDFInfo
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- CN113274344A CN113274344A CN202110725257.3A CN202110725257A CN113274344A CN 113274344 A CN113274344 A CN 113274344A CN 202110725257 A CN202110725257 A CN 202110725257A CN 113274344 A CN113274344 A CN 113274344A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
-
- 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
- A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
-
- 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
- A61M2037/0046—Solid microneedles
-
- 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
Abstract
The invention belongs to the technical field of administration micro-processing, and particularly relates to a bubble type hollow microneedle and a preparation method thereof. According to the bubble type hollow microneedle provided by the invention, the needle point and the needle body containing bubbles are integrally formed on the substrate and are easy to be removed from the mould, and meanwhile, the eight-pyramid-shaped bubbles are more adaptive to the microneedle main body with a cone structure than the elliptical-shaped bubbles, so that the eight-pyramid-shaped bubbles have larger volume and can be closer to the needle point, and the drug can be maximally enriched to the needle point. The preparation method of the bubble type hollow microneedle provided by the invention adopts one-step preparation, is prepared by controlling the viscosity, the vacuum degree and the vacuum time of a microneedle solution, is simple to operate and is prepared at normal temperature, the needle point and the needle body containing bubbles are prepared from the same material at one time, the connectivity is good, and the mold stripping is easy.
Description
Technical Field
The invention belongs to the technical field of administration micro-processing, and particularly relates to a bubble type hollow microneedle and a preparation method thereof.
Background
The therapeutic action of the drug depends on the drug itself, and the drug delivery system has very important influence on the exertion of drug effect, and for the biomacromolecule drugs such as polypeptide, protein, DNA, vaccine and the like represented by insulin, the oral administration bioavailability is very low and the curative effect cannot be achieved due to the influence of the degradation of enzymes in the gastrointestinal tract, the first pass effect of the liver and the like. Subcutaneous injection can conveniently and quickly inject large dose of medicine into a human body and can make up for the defects of oral administration, but has the limitations that the administration process has obvious pain, the injection point is damaged, the injection needs special technology and the continuous administration is difficult to realize, and patients, particularly children patients, usually have the fear of needles and are not suitable for long-term administration. Transdermal drug delivery systems, also known as transdermal therapeutic systems, are formulations in which the drug is absorbed at a rate through the skin via the capillaries into the systemic circulation to produce a therapeutic effect. Transdermal administration has many advantages over traditional modes of administration: can generate lasting, constant and controllable blood concentration, obviously improve the activity of the drug with short half-life period due to rapid metabolism in vivo, avoid the interference of the first pass effect of the liver and gastrointestinal tract factors, and reduce the toxic and side effect to the minimum; the medicine has the advantages of painlessness, no wound or minimal invasion, self administration by patients, convenient use, interruption of administration at any time, high patient compliance and the like, thereby becoming one of all new dosage forms with the highest growth speed. The transdermal drug delivery has a wide application range, has huge scale of global business market, has strong potential, and greatly increases the demand in chronic disease management in the global population aging trend.
Although transdermal drug delivery has great promise, there are only about twenty drugs currently on the market, mainly because the barrier effect of the stratum corneum, which is about 30-50 microns thick on the outermost layer of human skin, results in a too low transdermal permeation rate for most drugs to meet the therapeutic needs. The main route of percutaneous penetration and absorption of the medicine is sweat gland, epidermal penetration, hair follicle and its subsidiary sebaceous gland, and the skin subsidiary apparatus comprises hair follicle, sweat gland and sebaceous gland, which occupies about 0.1% of the skin area and has small contribution to percutaneous absorption. Drugs that can be transdermally administered at present are limited in many ways, for example, they have a molecular weight of less than 500D, are highly soluble, have a melting point of less than 150 ℃, and have a therapeutic dose of less than 20 mg/day, and passive transdermal administration of polymeric and polar drugs is difficult to achieve. At present, thousands of biomacromolecule medicines are being researched and developed internationally, and the lack of a proper drug delivery system becomes an important obstacle to the successful clinical entry and the market release of the biomacromolecule medicines due to the optimal curative effect.
The core of research on transdermal patches is how to overcome the stratum corneum barrier of the skin and promote transdermal absorption of drug molecules. In order to increase the permeability of the skin, various methods such as a chemical penetration enhancer, an iontophoresis method, and an electroporation method have been used. These methods all have varying degrees of limitations on the drug delivered, and some may also cause major toxic side effects. In recent years, the microneedle technology can directly break through the barrier of the stratum corneum of the skin to remarkably promote the transdermal absorption of various drug molecules including protein polypeptides, drug-loaded nanoparticles and the like, is a brand-new drug delivery technology integrating the advantages of injection and transdermal patches, and becomes a new transdermal drug delivery technology with the most application prospect. The microneedle transdermal drug delivery technology has the advantages of painlessness, minimally invasive property, safety, high efficiency, convenient carrying, self-use by patients and the like.
The materials of the micro-needle mainly comprise metal, silicon and biodegradable polymer. The administration modes are summarized into four types: firstly, solid or hollow microneedles are used for forming corresponding holes on the skin, then the medicines are pasted on a treatment part, and the microneedles which are administrated by the method are called pasting needles; secondly, the solid micro-needle is coated with the drug and then injected into the body of a patient, and the micro-needle administered in the way is often called as a coated micro-needle; thirdly, wrapping the drug in biodegradable polymer micro-needles, and then pricking the micro-needles into the skin of a patient for drug delivery, wherein the micro-needles applying the drug delivery mode are wrapped drug micro-needles; fourthly, micro-injection is carried out through the hollow micro-needle, and the micro-needle is called as a micro-injection mode drug administration micro-needle.
Bubble type micropins appear in the existing market, and the concentration rate of the medicine at the upper end of the needle body can be improved by forming bubbles on the main body part of the micropins, so that the medicine is not diffused downwards, and the medicine carrying efficiency is improved. The existing bubble type microneedles are prepared by adopting a two-step method, namely, a layer of soluble microneedle solution is poured on a mold to form a needle tip part, the microneedle body and a bubble structure of the microneedle are filled in vacuum, and then are frozen and dried, a non-woven fabric with medical double-sided adhesive on a single surface is adhered to a microneedle substrate, and the microneedles are subjected to demoulding to prepare the bubble type microneedles.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a bubble type hollow microneedle and a preparation method thereof, aiming at solving the technical problems that the existing bubble type microneedle is prepared by adopting a two-step method, the process is complicated, the freeze drying is needed, the needle tip and the needle body with bubbles are made of different materials, and the needle body is difficult to remove from a mold during demoulding.
The invention provides a bubble type hollow microneedle, which has the following specific technical scheme:
hollow micropin of bubble type, distribute including base and a plurality of array microneedle main part on the base, the micropin main part is the toper, the micropin main part includes needle body and needle point, the inside bubble that is formed with of needle body, the bubble is eight pyramid structures, the base the needle body with the needle point all is the integrated into one piece setting.
In certain embodiments, a plurality of the microneedle bodies are arranged in an annular array. Therefore, the finished microneedle patch is circular, the annular array structure is convenient to cut, and the microneedle main body cannot be cut.
In some embodiments, the height of the microneedle body perpendicular to the substrate is 300-.
The invention also provides a preparation method of the bubble type hollow microneedle, which is used for preparing the microneedle and comprises the following steps:
s1, preparing 2-5% microneedle preparation liquid from a microneedle preparation material, wherein the microneedle preparation material is one or more of sodium hyaluronate, polyvinyl alcohol, sodium methylcellulose and trehalose;
s2, coating the microneedle making solution of step S1 on a female mold at atmospheric pressure to obtain a solution-coated mold;
s3, placing the mould which is fully coated with the solution in the step S2 into a vacuum box, vacuumizing to 0.1-0.5P0, and maintaining for 10-30S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air-blowing drying oven for drying for 6 hours at 40 ℃, and removing the bubble type hollow microneedle after drying.
In some embodiments, in step S1, the microneedle preparation solution is stored at room temperature by removing air bubbles from the solution under vacuum.
In certain embodiments, in step S2, the microneedle making fluid has a mass of 10-40 g.
The invention has the following beneficial effects: according to the bubble type hollow microneedle provided by the invention, the needle point and the needle body containing bubbles are integrally formed on the substrate and are easy to be removed from the mould, and meanwhile, the eight-pyramid-shaped bubbles are more adaptive to the microneedle main body with a cone structure than the elliptical-shaped bubbles, so that the eight-pyramid-shaped bubbles have larger volume and can be closer to the needle point, and the drug can be maximally enriched to the needle point. The preparation method of the bubble type hollow microneedle provided by the invention adopts one-step preparation, is prepared by controlling the viscosity, the vacuum degree and the vacuum time of a microneedle solution, is simple to operate and is prepared at normal temperature, the needle point and the needle body containing bubbles are prepared from the same material at one time, the connectivity is good, and the mold stripping is easy.
Drawings
Fig. 1 is a flowchart of a method for preparing a bubble type hollow microneedle of the present invention;
FIG. 2 is a schematic plan view of a bubble type hollow microneedle provided by the present invention;
FIG. 3 is an electron microscope image of a bubble type hollow microneedle according to example 1 of the present invention;
FIG. 4 is a schematic plan view showing the structure of a bubble type hollow microneedle according to example 2 of the present invention;
fig. 5 is a schematic plan view of a bubble type hollow microneedle according to example 3 of the present invention.
Detailed Description
In order that the objects, aspects and advantages of the present invention will become more apparent, the present invention will be further described in detail with reference to the following detailed description of preferred embodiments thereof, with reference to the accompanying drawings of fig. 1-5.
Example 1
The bubble type hollow microneedle provided by the embodiment has the following specific technical scheme:
bubble type hollow micropin, including base and the micropin main part of a plurality of array distribution on the base, the micropin main part is the toper, and the micropin main part includes needle body and needle point, and the needle body is inside to be formed with the bubble, and the bubble is eight pyramid structures, and base, needle body and needle point all are integrated into one piece and set up.
Specifically, the plurality of microneedle bodies are arranged in an annular array. The height of the microneedle body perpendicular to the substrate was 400 μm, the vertical height of the air bubbles was 150 μm, and the distance of the bottom end of the air bubbles from the substrate was 30 μm.
The embodiment provides a preparation method of the bubble type hollow microneedle, and the specific scheme is as follows:
the preparation method of the bubble type hollow microneedle comprises the following steps:
s1, preparing a 3% sodium hyaluronate solution (microneedle preparation solution), removing bubbles in the solution under vacuum, and standing at room temperature;
s2, coating 20g of the microneedle making solution in the step S1 on a female mold with the depth of 400 μm and the period of 800 μm under atmospheric pressure to obtain a mold full of the solution;
s3, placing the mould which is fully coated with the solution in the step S2 in a vacuum box, vacuumizing to 0.1P0, and maintaining for 30S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air drying oven for drying for 6 hours at 40 ℃, and uncovering the bubble type hollow microneedle after drying. I.e. the microneedles described above.
Example 2
The bubble type hollow microneedle provided by the embodiment has the following specific technical scheme:
bubble type hollow micropin, including base and the micropin main part of a plurality of array distribution on the base, the micropin main part is the toper, and the micropin main part includes needle body and needle point, and the needle body is inside to be formed with the bubble, and the bubble is eight pyramid structures, and base, needle body and needle point all are integrated into one piece and set up.
Specifically, the plurality of microneedle bodies are arranged in an annular array. The height of the microneedle body perpendicular to the substrate was 400 μm, the vertical height of the air bubbles was 300 μm, and the distance of the bottom ends of the air bubbles from the substrate was 20 μm.
The embodiment provides a preparation method of the bubble type hollow microneedle, and the specific scheme is as follows:
the preparation method of the bubble type hollow microneedle comprises the following steps:
s1, preparing a 3% sodium hyaluronate solution (microneedle preparation solution), removing bubbles in the solution under vacuum, and standing at room temperature;
s2, coating 20g of the microneedle making solution in the step S1 on a female mold with the depth of 400 μm and the period of 800 μm under atmospheric pressure to obtain a mold full of the solution;
s3, placing the mould which is fully coated with the solution in the step S2 in a vacuum box, vacuumizing to 0.1P0, and maintaining for 10S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air drying oven for drying for 6 hours at 40 ℃, and uncovering the bubble type hollow microneedle after drying. I.e. the microneedles described above.
Example 3
The bubble type hollow microneedle provided by the embodiment has the following specific technical scheme:
bubble type hollow micropin, including base and the micropin main part of a plurality of array distribution on the base, the micropin main part is the toper, and the micropin main part includes needle body and needle point, and the needle body is inside to be formed with the bubble, and the bubble is eight pyramid structures, and base, needle body and needle point all are integrated into one piece and set up.
Specifically, the plurality of microneedle bodies are arranged in an annular array. The height of the microneedle body perpendicular to the substrate was 400 μm, the vertical height of the air bubbles was 200 μm, and the distance of the bottom end of the air bubbles from the substrate was 25 μm.
The embodiment provides a preparation method of the bubble type hollow microneedle, and the specific scheme is as follows:
the preparation method of the bubble type hollow microneedle comprises the following steps:
s1, preparing a 3% sodium hyaluronate solution (microneedle preparation solution), removing bubbles in the solution under vacuum, and standing at room temperature;
s2, coating 20g of the microneedle making solution in the step S1 on a female mold with the depth of 400 μm and the period of 800 μm under atmospheric pressure to obtain a mold full of the solution;
s3, placing the mould which is fully coated with the solution in the step S2 in a vacuum box, vacuumizing to 0.5P0, and maintaining for 30S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air drying oven for drying for 6 hours at 40 ℃, and uncovering the bubble type hollow microneedle after drying. I.e. the microneedles described above.
Example 4
The bubble type hollow microneedle provided by the embodiment has the following specific technical scheme:
bubble type hollow micropin, including base and the micropin main part of a plurality of array distribution on the base, the micropin main part is the toper, and the micropin main part includes needle body and needle point, and the needle body is inside to be formed with the bubble, and the bubble is eight pyramid structures, and base, needle body and needle point all are integrated into one piece and set up.
Specifically, the height of the microneedle body perpendicular to the substrate was 300 μm, the vertical height of the air bubble was 150 μm, and the distance of the bottom end of the air bubble from the substrate was 20 μm.
The embodiment provides a preparation method of the bubble type hollow microneedle, and the specific scheme is as follows:
the preparation method of the bubble type hollow microneedle comprises the following steps:
s1, preparing a 5% polyvinyl alcohol solution (microneedle preparation solution), removing bubbles in the solution under vacuum, and standing at room temperature;
s2, coating 10g of the microneedle making solution in the step S1 on a 800 μm period female die with the depth of 300 μm under atmospheric pressure to obtain a die full of the solution;
s3, placing the mould which is fully coated with the solution in the step S2 in a vacuum box, vacuumizing to 0.25P0, and maintaining for 15S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air drying oven for drying for 6 hours at 40 ℃, and uncovering the bubble type hollow microneedle after drying. I.e. the microneedles described above.
Example 5
The bubble type hollow microneedle provided by the embodiment has the following specific technical scheme:
bubble type hollow micropin, including base and the micropin main part of a plurality of array distribution on the base, the micropin main part is the toper, and the micropin main part includes needle body and needle point, and the needle body is inside to be formed with the bubble, and the bubble is eight pyramid structures, and base, needle body and needle point all are integrated into one piece and set up.
Specifically, the plurality of microneedle bodies are arranged in an annular array. The height of the microneedle body perpendicular to the substrate was 500 μm, the vertical height of the air bubbles was 300 μm, and the distance of the bottom ends of the air bubbles from the substrate was 30 μm.
The embodiment provides a preparation method of the bubble type hollow microneedle, and the specific scheme is as follows:
the preparation method of the bubble type hollow microneedle comprises the following steps:
s1, preparing a 2% trehalose solution (microneedle preparation solution), removing bubbles in the solution under vacuum, and standing at room temperature;
s2, coating 40g of the microneedle making solution in the step S1 on a 500-micron-depth 800-micron-period female die at atmospheric pressure to obtain a die full of the solution;
s3, placing the mould which is fully coated with the solution in the step S2 in a vacuum box, vacuumizing to 0.5P0, and maintaining for 30S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air drying oven for drying for 6 hours at 40 ℃, and uncovering the bubble type hollow microneedle after drying. I.e. the microneedles described above.
The above description is only for the purpose of illustrating preferred embodiments of the present invention and is not to be construed as limiting the invention, and the present invention is not limited to the above examples, and those skilled in the art should also be able to make various changes, modifications, additions or substitutions within the spirit and scope of the present invention.
Claims (6)
1. Bubble type hollow micropin, its characterized in that includes base and a plurality of array distribution microneedle main part on the base, the microneedle main part is the toper, the microneedle main part includes needle body and needle point, the inside bubble that is formed with of needle body, the bubble is eight pyramid structures, the base the needle body with the needle point all is the integrated into one piece setting.
2. The bubble type hollow microneedle according to claim 1, wherein a plurality of the microneedle bodies are arranged in an annular array.
3. A bubble type hollow microneedle according to claim 1, wherein the height of the microneedle body perpendicular to the substrate is 300-500 μm, the bubble vertical height is 150-300 μm, and the distance from the bottom end of the bubble to the substrate is 20-30 μm.
4. A method for producing a bubble type hollow microneedle, which is used for producing the microneedle according to any one of claims 1 to 3, comprising the steps of:
s1, preparing 2-5% microneedle preparation liquid from a microneedle preparation material, wherein the microneedle preparation material is one or more of sodium hyaluronate, polyvinyl alcohol, sodium methylcellulose and trehalose;
s2, coating the microneedle making solution of step S1 on a female mold at atmospheric pressure to obtain a solution-coated mold;
s3, placing the mould which is fully coated with the solution in the step S2 into a vacuum box, vacuumizing to 0.1-0.5P0, and maintaining for 10-30S to obtain a processing mould;
and S4, placing the processing mould in the step S3 in an air-blowing drying oven for drying for 6 hours at 40 ℃, and removing the bubble type hollow microneedle after drying.
5. The method of preparing bubble-type hollow microneedles in claim 4, wherein in step S1, the microneedle preparation solution is degassed under vacuum and stored at room temperature.
6. The method for preparing bubble-type hollow microneedles according to claim 4, wherein the mass of the microneedle preparation liquid in step S2 is 10-40 g.
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| CN106039552A (en) * | 2016-05-30 | 2016-10-26 | 北京化工大学 | Bubble-type microneedle and preparation method therefor |
| CN108939280A (en) * | 2018-04-13 | 2018-12-07 | 杭州电子科技大学 | A kind of preparation method of SU8 microneedle array patch |
| CN110025567A (en) * | 2019-05-21 | 2019-07-19 | 南京医科大学康达学院 | A kind of preparation method of autolyzed hyaluronic acid micropin |
| CN110478612A (en) * | 2019-07-15 | 2019-11-22 | 北京化工大学 | The method that tip dissolution method prepares the hollow administration micropin of bubble type |
-
2021
- 2021-06-29 CN CN202110725257.3A patent/CN113274344A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106039552A (en) * | 2016-05-30 | 2016-10-26 | 北京化工大学 | Bubble-type microneedle and preparation method therefor |
| CN108939280A (en) * | 2018-04-13 | 2018-12-07 | 杭州电子科技大学 | A kind of preparation method of SU8 microneedle array patch |
| CN110025567A (en) * | 2019-05-21 | 2019-07-19 | 南京医科大学康达学院 | A kind of preparation method of autolyzed hyaluronic acid micropin |
| CN110478612A (en) * | 2019-07-15 | 2019-11-22 | 北京化工大学 | The method that tip dissolution method prepares the hollow administration micropin of bubble type |
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