CN109529186B - Drug-coated amorphous alloy microneedle and manufacturing method thereof - Google Patents
Drug-coated amorphous alloy microneedle and manufacturing method thereof Download PDFInfo
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- CN109529186B CN109529186B CN201811544812.7A CN201811544812A CN109529186B CN 109529186 B CN109529186 B CN 109529186B CN 201811544812 A CN201811544812 A CN 201811544812A CN 109529186 B CN109529186 B CN 109529186B
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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
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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
- A61K47/02—Inorganic compounds
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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
- 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 utility model provides a drug coating metallic glass micropin, relates to medical instrument precision finishing and laser surface modification field, and its structure includes micropin array and basement, and the basement top is equipped with the micropin array, and the micropin array comprises a plurality of needle bodies, and the needle body is connected with the basement for the bottom surface of cone and needle body, every the side of needle body all is equipped with a plurality of micro-nano structure with the top surface of basement. The preparation method of the drug-coated amorphous alloy microneedle comprises the following steps: firstly, die-casting amorphous microneedles; then cleaning the surface of the microneedle; then, manufacturing a micro-nano structure on the bottom surface of the amorphous microneedle by using laser; then cleaning the processed microneedle; finally, the drug solution is adsorbed before injection. Based on the excellent characteristics of the micro-needle and the amorphous alloy, the invention can be used for manufacturing the amorphous micro-needle with high strength and low needle breakage probability by depending on medical amorphous alloy materials and laser micro-nano processing technology, can quickly adsorb medicinal solution, can accurately control dosage in medicament use, and is suitable for medicament injection such as insulin and the like.
Description
Technical Field
The invention relates to the field of precision machining and laser surface modification of medical instruments, in particular to a drug coating amorphous alloy microneedle and a manufacturing method thereof.
Background
In most studies, skin has shown promise for delivering Active Pharmaceutical Ingredients (APIs). Transdermal delivery has mainly the following advantages: efficient and precise controlled delivery, sustained release of the drug, avoidance of first liver metabolism and patient friendliness. Most APIs are fairly hydrophilic, charged or of large molecular size, making them far from ideal skin penetrants. Recent advances in transdermal drug delivery have therefore increased the need for strategies to overcome the Stratum Corneum (SC) barrier function of the skin in order to facilitate rapid, efficient penetration of a wider range of molecules, including macromolecular therapeutic agents and genetic material.
Microneedle arrays (MN) are minimally invasive devices that act on the Stratum Corneum (SC) to deliver drugs into the skin microcirculation and achieve systemic delivery via the transdermal route. The microneedles pierce the epidermis painlessly, creating microscopic pores of moisture through which the drug penetrates into the dermal microcirculation. Studies have shown that MN can be inserted into the skin without the need for an additional applicator device. The solid MN either punctured the skin prior to application of the drug loaded patch or was pre-coated with the drug prior to insertion.
The amorphous alloy has the characteristics of high corrosion resistance, good biocompatibility, good mechanical property and the like, and is suitable for manufacturing metal medical instruments. However, the conventional processing method may destroy the amorphous state of the amorphous alloy, resulting in the destruction of its excellent mechanical properties and corrosion resistance.
Microneedles that are currently widely used have the following problems: delivery of the active agent to the skin typically requires separate delivery to the dermal and epidermal layers, and prior art sequential procedures, i.e., epidermal and dermal layers, are time consuming. Meanwhile, for the micro-needle coated with the medicament before insertion, the surface affinity of the micro-needle to the water/oil-based medicament influences the adsorption amount of the medicament, so that the injection effect is also influenced to a certain extent. In addition, for the metal micro-needle, the needle breakage rate, the biocompatibility of the material and the like also have certain influence on the rejection reaction of the human body during injection.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide the drug coating amorphous alloy microneedle, which has the advantages of high microneedle strength, low needle breakage probability, better drug adsorption and drug delivery of a dermis layer and an epidermis layer. The second purpose of the invention is to provide a method for manufacturing the drug coating amorphous alloy microneedle, and the method can be used for preparing the microneedle with a micro-nano structure.
One of the purposes of the invention is realized by the following technical scheme:
the utility model provides a drug coating metallic glass micropin, including micropin array and basement, the basement top is equipped with the micropin array, and the micropin array comprises a plurality of needle bodies, and the needle body is connected with the basement for the bottom surface of cone and needle body, every the side of needle body all is equipped with a plurality of micro-nano structure with the top surface of basement.
The micro-nano structure is a super-hydrophilic micro-nano structure or an oleophylic micro-nano structure. The micro-nano structure with different hydrophilicity/lipophilicity can be prepared aiming at different medicines.
The processing depth of the super-hydrophilic micro-nano structure is 5-20 mu m, the structure period induced in the micro structure is 200-800nm, the induced structure depth is 0.1-0.3 mu m, and the contact angle of the surface is less than 1 degree.
The second purpose of the invention is realized by the following technical scheme:
the method for manufacturing the drug-coated amorphous alloy microneedle comprises the following steps:
s1, die casting the amorphous micro-needle,
s2, washing the surface of the microneedle,
s3, processing the micro-nano structure by laser,
s4, washing the micro-needle,
s5, adsorbing the drug solution before injection.
In the step of S1 die casting the amorphous microneedle, the rectangular drug coating amorphous alloy microneedle is manufactured by a die casting method, the raw material is repeatedly smelted for more than four times to ensure the uniformity of elements in the molten alloy, the temperature of the molten alloy is kept to be higher than 600K before die casting, and then the molten alloy enters a die casting die through a die casting runner in a vacuum environment of 10mbar for die casting.
The formula elements in the raw materials are metal elements with good biocompatibility and antibacterial activity, such as alloys containing Zr, Cu, Al, Ni, Ti, Ag and other elements. The hardness of the formed alloy is about 520 HV and 550HV, the bending strength reaches more than 1500MPa, and the elastic strain reaches more than 1.5 percent.
The die-casting mould material of the rectangular drug coating amorphous alloy microneedle adopts a rigid material with the thermal conductivity higher than 300W/Mk, the die-casting speed is higher than 3m/s, the cooling speed in the forming process is ensured to be higher than 300W/Mk, and the crystallization phenomenon is avoided.
In the step of cleaning the surface of the microneedle by the cleaning method of S2, in the step of S2, absolute ethyl alcohol is firstly used for cleaning for 15-30 minutes to remove the release agent, and then deionized water is used for cleaning for 5-10 minutes to remove the adhesive residue on the surface and drying.
In the step of processing the micro-nano structure by the S3 laser, the amorphous alloy micro-needle with the surface cleaned is processed by the ultra-fast laser to form the micro-nano structure.
The ultrafast laser is linearly polarized light, the laser pulse width is 100fs-20ps, the frequency is 50-200KHz, the laser single pulse energy range is 10-73 muJ, the spot diameter is 10-50 mu m, and the laser scanning speed is 50-500 mm/s.
In the step of cleaning the micro-needle S4, the drug-coated amorphous alloy micro-needle with the laser-processed hydrophilic micro-nano structure is ultrasonically cleaned in an ethanol solution for 5-20 minutes and is ultrasonically cleaned in deionized water for 5-10 minutes to remove material dust deposited on the surface after laser processing.
In the step of adsorbing the drug solution before the injection of S5, the surface of the drug coating amorphous alloy microneedle which is cleaned by ultrasonic is dropped into the injection drug solution, and the microneedle is injected after adsorbing the solution, wherein the concentration of the drug solution is 1000-40000U/ml.
The invention has the beneficial effects that: the substrate and the needle body surface of the drug-coated amorphous alloy microneedle are provided with the micro-nano structures, the micro-nano structures can store a certain amount of drug solution, the microneedle can pierce the epidermis painlessly to generate microscopic water pores, the drug permeates into dermal microcirculation through the micro-nano structures, meanwhile, the drug hidden in the micro-nano structures on the surface of the substrate can cover the surface of the skin, and the drug delivery of the dermal layer and the epidermal layer is carried out, the microneedle can accurately control the dosage in drug use and is suitable for the injection of the drugs such as insulin and the like, and the drug-coated amorphous alloy microneedle also has the following advantages,
1. the ultrafast laser surface processing technology can induce a functional microstructure on the surface of the material, so that the superhydrophilicity of the material is realized, and the amorphous state of the material can be still maintained when the functional microstructure is manufactured on the amorphous surface, so that the mechanical property and the corrosion resistance of the material are ensured;
2. the surface nano hydrophilic/lipophilic structure can improve the drug loading capacity of the microneedle surface;
3. the laser-induced micro-nano structure on the surface of the amorphous material has certain antibacterial activity.
Further, the manufacturing method of the drug coating amorphous alloy microneedle provided by the invention is based on the excellent characteristics of the microneedle and the amorphous alloy, and depends on the medical amorphous alloy material and the laser micro-nano processing technology, and the method can manufacture the metal microneedle which is high in strength, small in needle breakage probability and better in drug adsorption.
Drawings
The invention is further illustrated by means of the attached drawings, but the embodiments in the drawings do not constitute any limitation to the invention, and for a person skilled in the art, other drawings can be derived on the basis of the following drawings without inventive effort.
Fig. 1 is a schematic structural view of a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 2 is a flowchart illustrating a method for fabricating a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 3 is a schematic view illustrating step S1 of a method for fabricating a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 4 is a schematic view illustrating step S2 of a method for fabricating a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 5 is a schematic view illustrating step S3 of a method for fabricating a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 6 is a schematic view illustrating step S4 of a method for fabricating a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 7 is a schematic view illustrating the coating of the drug in step S5 of the method for manufacturing a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 8 is a schematic view illustrating injection in step S5 of the method for manufacturing a drug-coated amorphous alloy microneedle according to the present invention.
Fig. 9 shows a topography of a scanning electron microscope for laser processing a hydrophilic micro-nano structure in step S3 in four embodiments of the method for manufacturing a drug-coated amorphous alloy microneedle according to the present invention.
Which comprises the following steps:
0, die-casting the flow passage,
01 the needle body is fixed on the needle body,
021 an upper die is arranged on the upper die,
022 the lower die is arranged on the lower die,
a substrate 03 having a plurality of conductive layers thereon,
04 (a) an array of microneedles,
1, cleaning a solution by using absolute ethyl alcohol,
11 of the residual amount of the mold release agent,
12 of deionized water, and a reaction solution,
13 of the residues of the washing of the water,
2 a dynamic focusing field lens, and a focusing lens,
21 pulses of the laser light are emitted,
22 a micro-nano structure is adopted,
3 depositing the material after the processing of the alloy,
31 the residue left after the cleaning is carried out,
4, the medicine solution is added into the solution,
41 the skin of a subject to be treated,
42 the drug particles diffuse.
Detailed Description
The invention is further described with reference to the following examples.
The drug coating amorphous alloy microneedle of this embodiment, referring to fig. 1, including microneedle array 04 and base 03, base 03 top is equipped with microneedle array 04, and microneedle array comprises a plurality of needle bodies 01, and the needle body 01 is connected with base 03 for the bottom surface of cone and needle body 01, every the side of needle body 01 all is equipped with a plurality of micro-nano structure 22 with the top surface of base.
The micro-nano structure 22 is specifically a super-hydrophilic micro-nano structure or an oleophylic micro-nano structure.
The processing depth of the super-hydrophilic micro-nano structure is 5-20 mu m, the induced structure in the micro structure is of a sine curve structure, the period of the induced structure is 200-800nm, the induced structure depth is 0.1-0.3 mu m, and the contact angle of the surface is less than 1 degree.
The ultrafast laser surface processing technology can induce a functional microstructure on the surface of a material, so that the superhydrophilic property of the material is realized, and the amorphous state of the material can be still maintained when the functional microstructure is manufactured on the amorphous surface, so that the mechanical property and the corrosion resistance of the material are ensured, the surface nano hydrophilic/oleophilic structure can improve the drug loading capacity of the microneedle surface, and the laser-induced micro-nano structure on the surface of the amorphous material has certain antibacterial activity.
Example 1.
Referring to fig. 2 to 9, the method for manufacturing the amorphous alloy microneedle with the drug coating in this embodiment selects Zr, Cu, and Al as raw materials to manufacture the amorphous alloy microneedle with the drug coating, and the amorphous alloy microneedle with the drug coating has good strength and toughness, low cost, and is quite economical, and the manufacturing method thereof is as follows:
step S1 is performed first. Zr, Cu and Al are used as raw material formula elements, and the smelting is repeated for 5 times to fully mix all the elements in the raw materials. Copper is selected as an upper die 021 and a lower die 022, the thermal conductivity of the dies is about 500W/Mk, the dies are die-cast through a die-casting flow channel 0 in a vacuum environment of 10mbar, the die-casting speed is 5m/s, the temperature before the material is die-cast reaches 730K, the die-cast microneedle array 04 and a substrate 03 are formed in one step, the length of a needle body 01 is 900 micrometers, the diameter of the bottom of the needle body 01 is 300 micrometers, the distance between the centers of the needlepoints of the needle body 01 is 500 micrometers, and the thickness of the substrate 03 is 1.5. The surface roughness Ra of the tip cone after die casting is 0.1 mu m.
Then, step S2 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. The mold release agent 11 remaining was removed by washing with absolute ethanol wash 1 for 20 minutes. Then, rinsing with deionized water 12 for 10 minutes to remove the rinsing residue 13.
Then, step S3 is executed. And (3) performing microstructure processing on the conical surface of the needle body and the substrate by using an ultrafast laser system of the dynamic focusing field lens 2. The laser pulse 21 is linearly polarized light, the wavelength is 1030nm, the pulse width is 200fs, the frequency is 100KHz, the scanning linear velocity is 170mm/s, the single pulse energy is 5.2 muJ, and the processed hole wall of the micro-nano structure 22 has no crystallization phenomenon.
Then, step S4 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. And (3) cleaning the workpiece for 10 minutes by using an absolute ethyl alcohol cleaning solution 1 to remove the processed deposition material 3. The post-rinse residue 31 is then removed by rinsing in deionized water 12 for 10 minutes.
Then, step S5 is executed. The drug solution 4 having a concentration of 10000U/ml was infiltrated before injection, and then injection was performed on the skin 41 to allow the drug particles 42 to permeate the skin.
Example 2.
Referring to fig. 2 to 9, compared with example 1, in the method for manufacturing a drug-coated amorphous alloy microneedle of this embodiment, nickel is doped in an amorphous alloy raw material to prepare the drug-coated amorphous alloy microneedle, the drug-coated amorphous alloy microneedle has higher toughness, and is not prone to needle breakage, and the manufacturing method thereof is as follows:
step S1 is performed first. Selecting Zr, Cu, Al and Ni as raw material formula elements, and repeatedly smelting for 5 times to fully mix all the elements in the raw materials. Copper is selected as an upper die 021 and a lower die 022, the thermal conductivity of the dies is about 450W/Mk, the dies are die-cast through a die-casting flow channel 0 in a vacuum environment of 10mbar, the die-casting speed is 4.3m/s, the temperature of the materials before die-casting reaches 700K, the die-cast microneedle array 04 and a substrate 03 are formed in one step, the length of a needle body 01 is 600 micrometers, the diameter of the bottom of the needle body 01 is 200 micrometers, the distance between the centers of the needle bodies 01 is 500 micrometers, and the thickness of the substrate 03 is 1 mm. The surface roughness Ra of the tip cone after die casting is 0.1 mu m.
Then, step S2 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. The mold release agent 11 remaining was removed by washing with absolute ethanol wash 1 for 20 minutes. Then, rinsing with deionized water 12 for 10 minutes to remove the rinsing residue 13.
Then, step S3 is executed. And (3) performing microstructure processing on the conical surface of the needle body and the substrate by using an ultrafast laser system of the dynamic focusing field lens 2. The laser pulse 21 is linearly polarized light, the wavelength is 1030nm, the pulse width is 200fs, the frequency is 100KHz, the scanning linear velocity is 200mm/s, the single pulse energy is 2.5 muJ, and the micro-nano structure 22 has no crystallization phenomenon on the processed hole wall.
Then, step S4 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. And (3) cleaning the workpiece for 10 minutes by using an absolute ethyl alcohol cleaning solution 1 to remove the processed deposition material 3. The post-rinse residue 31 is then removed by rinsing in deionized water 12 for 10 minutes.
Then, step S5 is executed. The drug solution 4 having a concentration of 10000U/ml was infiltrated before injection, and then injection was performed on the skin 41 to allow the drug particles 42 to permeate the skin.
Example 3.
Referring to fig. 2 to 9, compared with example 2, in the method for manufacturing a drug-coated amorphous alloy microneedle of this embodiment, titanium is doped in an amorphous alloy raw material, so that the drug-coated amorphous alloy microneedle has good biocompatibility, and the titanium alloy has high strength, good toughness and excellent plasticity, is an ideal medical material, is also widely applied to the fields of artificial bones and the like, and is specifically manufactured as follows:
step S1 is performed first. Using Zr, Cu, Al, Ni and Ti as raw material formula elements, and repeatedly smelting for 5 times to fully mix all the elements in the raw materials. Copper is selected as an upper die 021 and a lower die 022, the thermal conductivity of the dies is about 450W/Mk, the dies are die-cast through a die-casting flow channel 0 in a vacuum environment of 10mbar, the die-casting speed is 4.5m/s, the temperature of the materials before die-casting reaches 700K, the die-cast microneedle array 04 and a substrate 03 are formed in one step, the length of the needle point of a needle body 01 is 500 mu m, the diameter of the bottom of the needle point of the needle body 01 is 250 mu m, the distance between the centers of the needle points of the needle body 01 is 400 mu m, and the. The surface roughness Ra of the tip cone after die casting is 0.1 mu m.
Then, step S2 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. The mold release agent 11 remaining was removed by washing with an absolute ethanol washing solution 1 for 20 minutes. Then, washing with deionized water 12 was performed for 10 minutes to remove the washed residue 13.
Then, step S3 is executed. And (3) performing microstructure processing on the conical surface of the needle body and the substrate by using an ultrafast laser system of the dynamic focusing field lens 2. The laser pulse 21 is linearly polarized light, the wavelength is 1030nm, the pulse width is 200fs, the frequency is 100KHz, the scanning linear velocity is 120mm/s, the single pulse energy is 3.8 muJ, and the micro-nano structure 22 has no crystallization phenomenon on the processed hole wall.
Then, step S4 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. And (3) cleaning the workpiece for 10 minutes by using an absolute ethyl alcohol cleaning solution 1 to remove the processed deposition material 3. The post-rinse residue 31 is then removed by rinsing in deionized water 12 for 10 minutes.
Then, step S5 is executed. The drug solution 4 having a concentration of 10000U/ml was infiltrated before injection, and then injection was performed on the skin 41 to allow the drug particles 42 to permeate the skin.
Example 4.
Referring to fig. 2 to 9, compared with example 2, in the method for manufacturing a drug-coated amorphous alloy microneedle of this embodiment, silver is doped in an amorphous alloy raw material, so that the drug-coated amorphous alloy microneedle has a bacteriostatic function, and the specific manufacturing method is as follows:
step S1 is performed first. Zr, Cu, Al, Ni and Ag are used as raw material formula elements, and the smelting is repeated for 5 times to fully mix all the elements in the raw materials. Die casting is carried out in a vacuum environment of 10mbar through a die casting flow channel 0, the die casting speed is 5m/s, and the temperature of the material reaches 730K before die casting. Copper is selected as an upper die 021 and a lower die 022, the thermal conductivity of the dies is about 370W/Mk, the die-cast microneedle array 04 and the substrate 03 are molded at one time, the length of the needlepoint of the needle body 01 is 700 mu m, the diameter of the bottom of the needlepoint of the needle body 01 is 300 mu m, the distance between the centers of the needlepoints of the needle body 01 is 500 mu m, and the thickness of the substrate 03 is 2 mm. The surface roughness Ra of the tip cone after die casting is 0.1 mu m.
Then, step S2 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. The mold release agent 11 remaining was removed by washing with absolute ethanol wash 1 for 20 minutes. Then, rinsing with deionized water 12 for 10 minutes to remove the rinsing residue 13.
Then, step S3 is executed. And (3) performing microstructure processing on the conical surface of the needle body and the substrate by using an ultrafast laser system of the dynamic focusing field lens 2. The laser pulse 21 is linearly polarized light, the wavelength is 1030nm, the pulse width is 200fs, the frequency is 100KHz, the scanning linear velocity is 230mm/s, the single pulse energy is 4.5 muJ, and the micro-nano structure 22 has no crystallization phenomenon on the processed hole wall.
Then, step S4 is executed. The cleaning process is carried out in an ultrasonic cleaning machine. And (3) cleaning the workpiece for 10 minutes by using an absolute ethyl alcohol cleaning solution 1 to remove the processed deposition material 3. The post-rinse residue 31 is then removed by rinsing in deionized water 12 for 10 minutes.
Then, step S5 is executed. The drug solution 4 having a concentration of 10000U/ml was infiltrated before injection, and then injection was performed on the skin 41 to allow the drug particles 42 to permeate the skin.
The manufacturing method of the drug coating amorphous alloy microneedle of the embodiment of the invention is based on the excellent characteristics of the microneedle and the amorphous alloy, and can manufacture the metal microneedle which is high in strength, small in needle breakage probability and better in drug adsorption by depending on the medical amorphous alloy material and the laser micro-nano processing technology.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (1)
1. A drug coating amorphous alloy microneedle is characterized by comprising a microneedle array and a substrate, wherein the microneedle array is arranged on the top of the substrate and consists of a plurality of needle bodies, the needle bodies are conical, the bottom surfaces of the needle bodies are connected with the substrate, and a plurality of micro-nano structures are arranged on the side surface of each needle body and the top surface of the substrate;
the micro-nano structure is a super-hydrophilic micro-nano structure or an oleophylic micro-nano structure;
the processing depth of the super-hydrophilic micro-nano structure is 5-20 mu m, the induced structure in the micro structure is of a sine curve structure, the period of the induced structure is 200-800nm, the induced structure depth is 0.1-0.3 mu m, and the contact angle of the surface is less than 1 degree;
the manufacturing method of the drug coating amorphous alloy microneedle comprises the following manufacturing steps:
s1, die-casting the amorphous alloy microneedle, manufacturing the amorphous alloy microneedle with the rectangular drug coating by a die-casting method, repeatedly smelting the microneedle raw material for more than four times to ensure the uniformity of elements in the raw material melt, pumping the inner cavity of the microneedle mould to a high vacuum of 10mbar, injecting the microneedle raw material into the microneedle mould from the die-casting runner for vacuum die-casting, and keeping the temperature of the alloy melt before die-casting higher than 600K; the formula elements of the amorphous alloy microneedle raw material are metal elements with good biocompatibility and antibacterial activity, the hardness of the formed alloy microneedle is 520-550HV, the bending strength reaches more than 1500MPa, and the elastic strain reaches more than 1.5%; the die-casting mould material of the rectangular drug coating amorphous alloy microneedle is a rigid material with the thermal conductivity higher than 300W/Mk, and the die-casting speed is higher than 3 m/s;
s2, cleaning the surface of the microneedle, ultrasonically cleaning the die-cast amorphous microneedle in an ethanol solution for 10-20 minutes, ultrasonically cleaning in deionized water for 5-15 minutes, and removing a release agent;
s3, processing a micro-nano structure by laser, and processing the micro-nano structure of the amorphous alloy micro-needle with the surface cleaned by ultrafast laser, wherein the ultrafast laser is linearly polarized light, the laser pulse width is 100fs-20ps, the frequency is 50-200KHz, the laser single pulse energy range is 10-73 muJ, the light spot diameter is 10-50 mu m, and the laser scanning speed is 50-500 mm/S;
s4, cleaning the micro-needle, ultrasonically cleaning the drug coating amorphous alloy micro-needle of the laser processing hydrophilic micro-nano structure in an ethanol solution for 5-20 minutes, ultrasonically cleaning in deionized water for 5-10 minutes, and removing material dust deposited on the surface after laser processing;
s5, adsorbing a drug solution before injection, immersing the surface of the amorphous alloy microneedle subjected to ultrasonic cleaning into the drug solution, and allowing the microneedle to adsorb the solution to form a drug coating.
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| CN111632195A (en) * | 2020-05-25 | 2020-09-08 | 北京航空航天大学 | Medical implant for improving cell osteogenesis performance and preparation method thereof |
| CN113101515B (en) * | 2021-04-06 | 2022-11-18 | 广州联合丽拓生物科技有限公司 | Method for processing beauty needle |
| CN113070576B (en) * | 2021-05-08 | 2022-01-28 | 吉林大学 | Method for preparing micro-nano periodic structure on surface of amorphous alloy by nanosecond laser irradiation |
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