CN114748779B - Microneedle and manufacturing process thereof - Google Patents
Microneedle and manufacturing process thereof Download PDFInfo
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- CN114748779B CN114748779B CN202210348221.2A CN202210348221A CN114748779B CN 114748779 B CN114748779 B CN 114748779B CN 202210348221 A CN202210348221 A CN 202210348221A CN 114748779 B CN114748779 B CN 114748779B
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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
-
- 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
- A61M2037/0023—Drug applicators 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
- A61M2037/0053—Methods for producing microneedles
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Micromachines (AREA)
Abstract
The invention discloses a microneedle and a manufacturing process thereof, wherein the manufacturing process of the microneedle comprises the following steps: a) Opening: etching a plurality of concave parts on the top surface of the substrate; b) Film forming: generating a needle body film layer on the top surface of the substrate, and simultaneously enabling part of the needle body film layer to sink into each concave part and respectively forming a hollow sinking structure or a solid sinking structure; c) And (3) hole opening: when the hollow sinking structures are formed, polishing the bottom surface of the substrate until the bottom of each hollow sinking structure is worn upwards and a hollow channel is formed; when the solid sinking structures are formed, etching is respectively carried out on the top surfaces of the solid sinking structures until the top surfaces penetrate through the bottom surface of the substrate and hollow channels are formed; d) De-lining: the substrate is removed. The invention can prepare a single microneedle or a microneedle array with a mechanical channel with a micron-sized size, and has simple, mature and stable overall preparation process and low preparation cost.
Description
[ Field of technology ]
The invention relates to the technical field of medical equipment, in particular to a microneedle and a manufacturing process thereof.
[ Background Art ]
The microneedle (Microneedles, MN) is a novel physical penetration-promoting technology, is formed by connecting a plurality of micron-sized tiny needlepoints on a base in an array manner, can directionally penetrate through a stratum corneum, generates a micron-sized mechanical channel, directly places a medicament on epidermis or an upper dermis layer, can participate in microcirculation without passing through the stratum corneum, exerts pharmacological reaction, is different from the traditional needle administration, does not generate pain, is convenient to administer, and can effectively improve the compliance of a patient.
According to the characteristics of the microneedles, the microneedles can be specifically classified into solid microneedles, hollow microneedles, coated microneedles, soluble microneedles, and hydrogel microneedles. Among them, hollow microneedles (Hollow microneedles), i.e., hollow microneedles, are essentially micro-scale micro-syringes. The medicine can be preloaded in the needle cavity of the hollow micro needle, and then automatically enters the body under the pressure drive of the tissue fluid concentration gradient after the needle tip of the hollow micro needle pierces the skin, so as to realize the delivery.
The hollow microneedle has the advantage of large drug loading capacity due to the hollow structure, however, the hollow microneedle is usually processed and prepared by adopting a digital control micro-electromechanical system, the whole preparation process is precise and complex, the preparation cost is high, the time consumption is long, and the large-scale popularization and the use are difficult, so that the problem is to be solved.
[ Invention ]
The invention aims to solve the problems in the prior art, and provides a microneedle and a manufacturing process thereof, which can prepare a single microneedle or a microneedle array with a mechanical channel with a micron-sized size, and the whole preparation process is simple, mature and stable, and has low preparation cost.
In order to achieve the above object, the present invention provides a manufacturing process of a microneedle, comprising the following steps:
a) Opening: etching a plurality of concave parts on the top surface of the substrate, wherein the concave parts can penetrate through the bottom surface or not penetrate through the bottom surface;
b) Film forming: generating a needle body film layer on the top surface of the substrate, and simultaneously enabling part of the needle body film layer to sink into each concave part and respectively forming a hollow sinking structure or a solid sinking structure;
c) And (3) hole opening: when the hollow sinking structures are formed, polishing the bottom surface of the substrate until the bottom of each hollow sinking structure is worn upwards and a hollow channel is formed; when the solid sinking structures are formed, etching is respectively carried out on the top surfaces of the solid sinking structures until the top surfaces penetrate through the bottom surface of the substrate and hollow channels are formed;
d) De-lining: the substrate is removed.
Preferably, in step a), the substrate is a glass substrate.
Preferably, in step a), each concave portion has an inverted cone shape, and each concave portion is etched by using a photoresist etching technique or a maskless etching technique.
Preferably, in the step b), the needle body film layer is formed by plating a pure metal film or an alloy film.
Preferably, the needle film layer is a pure metal film formed by chemical vapor deposition, such as a tungsten film or a titanium film.
Preferably, in step c), when forming the solid submerged structure, each of the hollow channels is etched by using photoresist etching technology or maskless etching technology.
Preferably, in step c), each hollow passage has a length of 100 to 1500 μm and a diameter of 1 to 200 μm.
Preferably, in step d), the substrate is washed away by chemical etching.
Preferably, the method further comprises the step of e) post-treatment: the nanoscale gold film coating is generated outside the hollow sinking structure or the solid sinking structure through physical sputtering or electroplating.
A microneedle manufactured by the foregoing manufacturing process.
The invention has the beneficial effects that:
1. According to the invention, a plurality of concave parts are etched on the top surface of the substrate, a needle membrane layer is generated on the top surface of the substrate, part of the needle membrane layer is sunk into each concave part and forms a hollow sunk structure or a solid sunk structure respectively, a hollow channel is formed in the hollow sunk structure or the solid sunk structure in a polishing or etching mode, finally, after the substrate is removed, a single microneedle or microneedle array with a mechanical channel with a micron-sized size is obtained, and can effectively penetrate through a stratum corneum when in use, the medicine is directly placed in epidermis or upper dermis, and the medicine is slowly released into the body by utilizing the driving force formed by the concentration gradient between the medicine and subcutaneous tissue liquid, so that pharmacological reaction is exerted, and the whole preparation process is simple, mature and stable, and the preparation cost is low;
2. the concave part is designed to be in an inverted cone shape, so that the conical hollow microneedle can be formed conveniently and finally, the effective penetrating power is ensured, the volume can be increased, the drug loading capacity is improved, and the release speed is regulated to realize accurate drug delivery;
3. Etching a plurality of concave parts which do not penetrate through the bottom surface on the top surface of the substrate by adopting an optical cement etching technology or a maskless etching technology, and adjusting the etching area, the etching duration and the etching quantity according to the treatment requirement so as to realize personalized accurate control on the length and the shape of a single microneedle and the quantity of the microneedles in a unit area in a microneedle array;
4. The needle body film layer is formed by plating a pure metal film or an alloy film, so that the biocompatibility and mechanical property of the metal material can be utilized, and the long-time stable percutaneous administration can be realized;
5. by adopting a plating mode to generate a needle film layer on the top surface of the substrate, the thickness of the needle film layer can be controlled according to actual requirements;
6. The length of the microneedle is controlled to be 100-1500 mu m, and the diameter of the microneedle is controlled to be 1-200 mu m, so that the needle body can be ensured to be smoothly pricked into the skin, and the pain is avoided;
7. the nanoscale gold film coating is generated outside the hollow sinking structure or the solid sinking structure by utilizing a physical sputtering or electroplating mode, so that the conductivity and the chemical and biological stability can be effectively increased.
The features and advantages of the present invention will be described in detail by way of example with reference to the accompanying drawings.
[ Description of the drawings ]
FIG. 1 is a flow chart of a first embodiment;
FIG. 2 is a flow chart of a second embodiment;
FIG. 3 is a flow chart of a third embodiment;
fig. 4 is a flowchart of the fourth embodiment.
In the figure: 1-substrate, 11-concave part, 2-needle membrane layer, 21-hollow sinking structure, 22-solid sinking structure, 23-hollow channel, 3-photoresist layer and 31-through hole.
[ Detailed description ] of the invention
Embodiment one:
referring to fig. 1, a manufacturing process of a microneedle according to the present invention includes the steps of:
a) Opening: selecting a substrate 1 with proper thickness according to the requirement, and etching a plurality of concave parts 11 which do not penetrate through the bottom surface on the top surface of the substrate 1, wherein the substrate 1 is a glass substrate, each concave part 11 is in an inverted cone shape, and each concave part 11 is etched by adopting a maskless etching technology;
the maskless etching technology can be a laser etching technology, and can utilize high-energy-density laser to irradiate the top surface of the substrate 1, so that the surface material of the irradiated area is subjected to a series of complex physical and even chemical processes such as heating, melting, vaporizing, forming plasma, volatilizing, sputtering and the like, and finally the concave part 11 is formed;
b) Film forming: a needle film layer 2 is formed on the top surface of the substrate 1, and part of the needle film layer 2 is sunk into each concave part 11 to form a hollow sunk structure 21, and the needle film layer 2 is formed by plating a tungsten film.
C) And (3) hole opening: polishing the bottom surface of the substrate 1 until the bottom of each hollow sinking structure 21 is ground upwards to form hollow channels 23, wherein the length of each hollow channel 23 is 100-1500 mu m, and the diameter of each hollow channel 23 is 1-200 mu m;
d) De-lining: washing off the substrate 1 by chemical etching;
e) Post-treatment: a nano-scale gold thin film coating is produced outside the hollow sinker structure 21 by physical sputtering or electroplating.
A microneedle manufactured by the foregoing manufacturing process.
Embodiment two:
referring to fig. 2, a manufacturing process of the microneedle of the present invention comprises the following steps:
a) Opening: selecting a substrate 1 with proper thickness according to the requirement, and etching a plurality of concave parts 11 which do not penetrate through the bottom surface on the top surface of the substrate 1, wherein the substrate 1 is a glass substrate, each concave part 11 is in an inverted cone shape, and each concave part 11 is etched by adopting an photoresist etching technology;
The photoresist etching technology specifically comprises the steps of firstly coating photoresist on the top surface of a substrate 1 and forming a photoresist layer 3, after drying, shielding by using a mask, so that light irradiates a partial region of the photoresist layer 3, dissolving the exposed or unexposed region of the photoresist layer 3 by using a developing solution and forming a through hole 31, and finally, using plasma generated under the action of an electric field to pass through the through hole 31 and bombard the top surface of the substrate 1 until a concave part 11 is generated;
b) Film forming: generating a needle film layer 2 on the top surface of the substrate 1, and simultaneously enabling part of the needle film layer 2 to sink into each concave part 11 and respectively forming a hollow sinking structure 21, wherein the needle film layer 2 is formed by plating a tungsten film;
c) And (3) hole opening: polishing the bottom surface of the substrate 1 until the bottom of each hollow sinking structure 21 is ground upwards to form hollow channels 23, wherein the length of each hollow channel 23 is 100-1500 mu m, and the diameter of each hollow channel 23 is 1-200 mu m;
d) De-lining: washing off the substrate 1 by chemical etching;
e) Post-treatment: a nano-scale gold thin film coating is produced outside the hollow sinker structure 21 by physical sputtering or electroplating.
A microneedle manufactured by the foregoing manufacturing process.
Embodiment III:
Referring to fig. 3, a manufacturing process of the microneedle of the present invention comprises the following steps:
a) Opening: selecting a substrate 1 with proper thickness according to the requirement, and etching a plurality of concave parts 11 which do not penetrate through the bottom surface on the top surface of the substrate 1, wherein the substrate 1 is a glass substrate, each concave part 11 is in an inverted cone shape, and each concave part 11 is etched by adopting a maskless etching technology;
the maskless etching technology can be a laser etching technology, and can utilize high-energy-density laser to irradiate the top surface of the substrate 1, so that the surface material of the irradiated area is subjected to a series of complex physical and even chemical processes such as heating, melting, vaporizing, forming plasma, volatilizing, sputtering and the like, and finally the concave part 11 is formed;
b) Film forming: generating a needle film layer 2 on the top surface of the substrate 1, and simultaneously enabling part of the needle film layer 2 to sink into each concave part 11 and respectively form a solid sinking structure 22, wherein the needle film layer 2 is formed by plating a tungsten film;
c) And (3) hole opening: etching the top surface of each solid sinking structure 22 until penetrating the bottom surface of the substrate 1 and forming hollow channels 23, wherein each hollow channel 23 is etched by a maskless etching technology (laser etching technology, the same as above), and the length of each hollow channel 23 is 100-1500 mu m, and the diameter is 1-200 mu m;
d) De-lining: washing off the substrate 1 by chemical etching;
e) Post-treatment: a nano-scale gold thin film coating is produced by physical sputtering or electroplating outside the solid sinker structure 22.
A microneedle manufactured by the foregoing manufacturing process.
Embodiment four:
Referring to fig. 4, a manufacturing process of the microneedle of the present invention comprises the following steps:
a) Opening: selecting a substrate 1 with proper thickness according to the requirement, and etching a plurality of concave parts 11 penetrating through the bottom surface on the top surface of the substrate 1, wherein the substrate 1 is a glass substrate, each concave part 11 is in an inverted cone shape, and each concave part 11 is etched by adopting a maskless etching technology;
the maskless etching technology can be a laser etching technology, and can utilize high-energy-density laser to irradiate the top surface of the substrate 1, so that the surface material of the irradiated area is subjected to a series of complex physical and even chemical processes such as heating, melting, vaporizing, forming plasma, volatilizing, sputtering and the like, and finally the concave part 11 is formed;
b) Film forming: generating a needle film layer 2 on the top surface of the substrate 1, and simultaneously enabling part of the needle film layer 2 to sink into each concave part 11 and respectively form a solid sinking structure 22, wherein the needle film layer 2 is formed by plating a tungsten film;
c) And (3) hole opening: etching the top surface of each solid sinking structure 22 until penetrating the bottom surface of the substrate 1 and forming hollow channels 23, wherein each hollow channel 23 is etched by a maskless etching technology (laser etching technology, the same as above), and the length of each hollow channel 23 is 100-1500 mu m, and the diameter is 1-200 mu m;
d) De-lining: washing off the substrate 1 by chemical etching;
e) Post-treatment: a nano-scale gold thin film coating is produced by physical sputtering or electroplating outside the solid sinker structure 22.
A microneedle manufactured by the foregoing manufacturing process.
The above embodiments are illustrative of the present invention, and not limiting, and any simple modifications of the present invention fall within the scope of the present invention.
Claims (6)
1. A process for manufacturing a microneedle, comprising the steps of:
a) Opening: etching a plurality of concave parts (11) on the top surface of the substrate (1); the substrate (1) is a glass substrate;
b) Film forming: generating a needle film layer (2) on the top surface of the substrate (1), and simultaneously, sinking part of the needle film layer (2) into each concave part (11) and forming a hollow sinking structure (21) or a solid sinking structure (22) respectively; the needle body film layer (2) is formed by plating a pure metal film or an alloy film; the pure metal film is a tungsten film or a titanium film deposited by chemical vapor deposition;
c) And (3) hole opening: when the hollow sinking structures (21) are formed, polishing the bottom surface of the substrate (1) until the bottom of each hollow sinking structure (21) is ground upwards and hollow channels (23) are formed; when the solid sinking structures (22) are formed, etching is respectively carried out on the top surfaces of the solid sinking structures (22) until the top surfaces penetrate through the bottom surface of the substrate (1) and hollow channels (23) are formed;
d) De-lining: removing the substrate (1);
e) Post-treatment: the nanoscale gold film coating is generated outside the hollow sinking structure (21) or the solid sinking structure (22) through physical sputtering or electroplating.
2. A process for manufacturing a microneedle according to claim 1, wherein: in the step a), each concave part (11) is in an inverted cone shape, and each concave part (11) is etched by adopting a photoresist etching technology or a maskless etching technology.
3. A process for manufacturing a microneedle according to claim 1, wherein: in step c), when forming the solid submerged structure (22), each hollow channel (23) is etched by photoresist etching or maskless etching.
4. A process for manufacturing a microneedle according to claim 1, wherein: in step c), each hollow channel (23) has a length of 100 to 1500 μm and a diameter of 1 to 200 μm.
5. A process for manufacturing a microneedle according to claim 1, wherein: in step d), the substrate (1) is washed away by chemical etching.
6. A microneedle, characterized in that: manufactured by the manufacturing process according to any one of claims 1 to 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210348221.2A CN114748779B (en) | 2022-04-01 | 2022-04-01 | Microneedle and manufacturing process thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210348221.2A CN114748779B (en) | 2022-04-01 | 2022-04-01 | Microneedle and manufacturing process thereof |
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| Publication Number | Publication Date |
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| CN114748779A CN114748779A (en) | 2022-07-15 |
| CN114748779B true CN114748779B (en) | 2024-09-03 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115227957A (en) * | 2022-07-26 | 2022-10-25 | 空芯微医疗科技(上海)有限责任公司 | Preparation method and product of hollow microneedle |
| CN115227956A (en) * | 2022-07-26 | 2022-10-25 | 空芯微医疗科技(上海)有限责任公司 | Preparation method of hollow microneedle |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6551849B1 (en) * | 1999-11-02 | 2003-04-22 | Christopher J. Kenney | Method for fabricating arrays of micro-needles |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6663820B2 (en) * | 2001-03-14 | 2003-12-16 | The Procter & Gamble Company | Method of manufacturing microneedle structures using soft lithography and photolithography |
| US20050011858A1 (en) * | 2003-07-16 | 2005-01-20 | Industrial Technology Research Institute | Method for fabricating a hollow micro-needle array |
| CN101342404B (en) * | 2008-08-28 | 2010-04-14 | 上海交通大学 | Fabrication method of heteroplanar metal hollow microneedles for transdermal drug delivery |
| KR101251927B1 (en) * | 2010-01-22 | 2013-04-08 | 오형훈 | Fabrication Method of Microneedle |
| CN108096699B (en) * | 2017-12-28 | 2020-12-01 | 浙江大学台州研究院 | Hollow microneedle array for drug delivery and body fluid collection and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6551849B1 (en) * | 1999-11-02 | 2003-04-22 | Christopher J. Kenney | Method for fabricating arrays of micro-needles |
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