CN105833424A - Silk fibroin micro-needle patch and preparation method thereof - Google Patents
Silk fibroin micro-needle patch and preparation method thereof Download PDFInfo
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- CN105833424A CN105833424A CN201610161394.8A CN201610161394A CN105833424A CN 105833424 A CN105833424 A CN 105833424A CN 201610161394 A CN201610161394 A CN 201610161394A CN 105833424 A CN105833424 A CN 105833424A
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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
- 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
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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
- A61M2037/0046—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
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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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention belongs to the field of medical beauty micro-needles, and in particular relates to a silk fibroin micro-needle patch and a preparation method thereof. The silk fibroin micro-needle patch comprises a backing layer, a micro-needle layer and a pressure-sensitive adhesive coating by which the backing layer and the micro-needle layer are stuck, wherein a plurality of needle-shaped bumps, which are uniformly distributed, are arranged on the micro-needle layer; needle-shaped cavities are formed in the needle-shaped bumps; the volume of the needle-shaped cavities is 40-90% of the volume of the needle-shaped bumps; medicines are kept in the needle-shaped cavities; the micro-needle layer is made from silk fibroin, and the molecular weight of the silk fibroin is lower than 100,000; the silk fibroin micro-needle patch is excellent in mechanical performance under a dry state, the silk fibroin micro-needle patch is sufficient in strength to penetrate into skin, and since the molecular weight of the silk fibroin is lower than 100,000, the micro-needle patch is high in dissolving rate, and as the micro-needle patch penetrates into the skin and gets into contact with body liquid, the micro-needle layer can rapidly dissolve, and subsequently, the medicines can get into contact with the body liquid and can dissolve in and disperse to the inner side of epidermis; therefore, the silk fibroin micro-needle patch is applicable to symptoms which require the rapid release of the medicines and have a relatively high requirement on a blood medicine dose.
Description
Technical field
The invention belongs to medical and beauty treatment micropin field, particularly relate to a kind of fibroin albumen microneedle patch and preparation side thereof
Method.
Background technology
Nowadays people increasingly pay attention to the maintenance of skin, particularly eye part skin, and periocualr skin is slim, hold most
The most aging and come into question.Conventional eye part skin maintenance medicine mostly is macromolecular drug, it is difficult to through eye
Skin enters subcutaneous, relatively low hence with rate.
Micropin is that the micron order of a kind of similar injection needle is hollow or solid needle, is made by fine process
Forming, diameter, in 30~80 μm, is about hundreds of micron.It can not touch the pain sensation through horny layer just
Nerve, does not creates a painful feeling and skin injury while rush oozes effect playing, and is to beat on keratodermatitis
Open passage vertical, visible.He has a very wide range of purposes clinically, it is adaptable to insulin, interferon,
The administration of the medicines such as biologics and vaccine such as antibody.
Preferably thrust to change skin permeation performance though conventional metals, glass, the entity micropin such as siliceous possess
Power, but typically medicine is applied in microneedle surface, and drug loading is little, it is difficult to reach therapeutic effect.Tradition gold
Genus, glass, silicon dioxide, siliceous and polymeric hollow micropin can be improved by the method for additional drug storage warehouse
Entity micropin is low at carrying drug ratio, medicine controlled releasing difference defect, but need complexity plating, photoengraving,
Wet etching, microchannel placingJi Shu and the complicated technology such as insertion mould preparation and use, relatively costly,
Be not suitable for large batch of production.
Because above-mentioned defect, the design people, the most in addition research and innovation, to founding a kind of fibroin egg
White microneedle patch and preparation method thereof so that it is have more the value in industry.
Summary of the invention
For solving above-mentioned technical problem, it is an object of the invention to provide a kind of fibroin albumen microneedle patch and preparation thereof
Method, the microneedle patch drug loading obtained is high, injection speed is fast, with low cost.
A kind of fibroin albumen microneedle patch that the present invention proposes, including backing layer, micropin layer, bond described backing
Layer and the pressure-sensitive adhesive coating of micropin layer, it is protruding that described micropin layer is provided with several evenly distributed needle-likes, described
Being provided with needle-like cavity in needle-like projection, the volume of described needle-like cavity accounts for the 40-90% of described needle-like projection volume,
Being provided with medicine in described needle-like cavity, the material of described micropin layer is fibroin albumen, the molecular weight of fibroin albumen
Less than 100,000.
Further, the wall thickness of described micropin layer is 5-40 μm, and the adjacent spacing of described needle-like projection is
0.1-1mm, height are for 200-400 μm, tip diameter is not more than 10 μm, half high diameter is not more than 50 μ
m。
Further, described medicine includes ibuprofen, aspirin, albumen, polypeptide drug insulin,
Any one in blood digestive enzyme, vaccine, immune protein, growth hormone, hyaluronic acid, creotoxin.
Further, described pressure-sensitive adhesive coating is waterproof pressure sensitive gel coating.
Further, the material of described backing layer is flexible nonwoven cloth or PUR film.
The invention allows for the preparation method of a kind of fibroin albumen microneedle patch, comprise the following steps:
1) preparation of little molecule silk fibroin solution: be the Na of 0.25% as mass fraction by silkworm cocoon2CO3Molten
In liquid, repeat to boil at 98~100 DEG C three times, each 30min, and be washed with deionized water clean, by degumming also
Fibroin after drying is dissolved in 9.3M lithium-bromide solution by the bath raio of 1:10 at 60 DEG C, is concentrated into after dialysis
0.09g/mL;
2) preparation of micropin layer: by little molecule silk fibroin protein solution that concentration is 0.09g/mL by 4.5~10.5mg
Every 15*15 array is cast in polydimethylsiloxane mould, true under the vacuum degree condition more than 0.09MPa
After empty de-bubbled, constant temperature and humidity, temperature: 15~40 DEG C, relative humidity: 25~75%, it is dried more than 36h;
3) loading of medicine: solid drugs is first dissolved in respective volatile good solvent, described good solvent bag
Include in water, ethanol, chloroform any one, wiring solution-forming, be applied in step 2) described in micro-
Needle layer surface, more evacuated, freeze-day with constant temperature etc., make medicine enter needle-like cavity inside and make solvent volatilize;
Suspension, emulsion are filled: utilize the method for ultrasonic disperse to be dispersed in by insoluble solid powder medicaments
In volatile solvent, turbid liquid system more stable in making the short time, it is applied in step 2) described in
Micropin layer surface, more evacuated, freeze-day with constant temperature, make medicine enter needle-like cavity and make solvent volatilize;
4) preparation of pressure-sensitive adhesive coating and backing layer: by pressure-sensitive adhesives in step 3) described in encapsulation
The micropin layer back side of medicine, and backing layer in pressing, then it is taken off from polydimethylsiloxane die surface,
The most plastic through suitable cutting.
Further, described step 3) in, the medicine of loading directly can also be carried out with the state of pressed powder
Fill.
By such scheme, the present invention at least has the advantage that the volume of (1) its needle-like cavity accounts for needle-like
The 40-90% of protruding volume, drug loading is high;(2) material of micropin layer is fibroin albumen, mechanics under dry state
Excellent performance, possesses enough intensity and thrusts skin, and owing to its molecular weight is less than 100,000, its rate of dissolution is high,
After touching body fluid after thrusting skin, micropin layer dissolves rapidly, and then medicine touches body fluid and dissolves and diffuse to table
Intradermal side, is suitable for needing quick release and blood pharmaceutical quantities to require bigger symptom.
Described above is only the general introduction of technical solution of the present invention, in order to better understand the technology of the present invention
Means, and can being practiced according to the content of description, below with presently preferred embodiments of the present invention and coordinate attached
After figure describes in detail such as.
Accompanying drawing explanation
Fig. 1 is the structural representation of fibroin albumen microneedle patch in the present invention;
Fig. 2 is the scanning electron microscope (SEM) photograph of needle-like projection local in embodiment 2;
Fig. 3 is the scanning electron microscope (SEM) photograph at the microneedle patch back side in embodiment 2;
Fig. 4 is the scanning electron microscope (SEM) photograph before fibroin albumen microneedle patch thrusts in embodiment 2;
Scanning electron microscope (SEM) photograph when Fig. 5 is that in embodiment 2, fibroin albumen microneedle patch dissolves.
Detailed description of the invention
Below in conjunction with the accompanying drawings and embodiment, the detailed description of the invention of the present invention is described in further detail.With
Lower embodiment is used for illustrating the present invention, but is not limited to the scope of the present invention.
See Fig. 1, a kind of fibroin albumen microneedle patch that the present invention proposes, including backing layer 1, micropin layer 2,
Bonding backing layer 1 and the pressure-sensitive adhesive coating 3 of micropin layer 2, micropin layer 2 is provided with the needle-like that several are evenly distributed
Protruding 21, it is provided with needle-like cavity in needle-like projection 21, the volume of needle-like cavity accounts for protruding 21 volumes of needle-like
40-90%, is provided with medicine 4 in needle-like cavity, the material of micropin layer 2 is fibroin albumen, the molecule of fibroin albumen
Amount is less than 100,000.The wall thickness of micropin layer 2 is 5-40 μm, the adjacent spacing of needle-like projection 21 be 0.1-1mm,
Highly for 200-400 μm, tip diameter is not more than 10 μm, half high diameter is not more than 50 μm.Needle-like is empty
The medicine 4 of intracavity can be small-molecule drug 4, as having the cure cold ibuprofen of fever effect, aspirin,
Albumen, polypeptide drug 4 insulin, various blood digestive enzyme, vaccine, immune protein, growth hormone etc.,
Or improve looks crease-resistant biomacromolecule hyaluronic acid, creotoxin etc..Pressure-sensitive adhesive coating 3 is waterproof pressure sensitive glue
Coating 3, is additionally operable to during use be adhered fixed in skin surface microneedle patch.The material of backing layer 1 is soft
Property non-woven fabrics or PUR film.During use, microneedle patch being directly pasted on skin surface, needle-like projection thrusts skin
Skin, release is wrapped in interior medicine.
The preparation method of above-mentioned fibroin albumen microneedle patch, is exemplified below:
Embodiment one
(1) preparation of little molecule silk fibroin solution: as 4000mL mass fraction be by the silkworm cocoon of 80g
The Na of 0.25%2CO3In solution, repeat to boil at 98~100 DEG C three times, each 30min, and with deionization
Water is cleaned.Fibroin after degumming drying is dissolved in 9.3M lithium-bromide solution by the bath raio of 1:10 at 60 DEG C,
It is concentrated into 0.09g/mL, as stand-by in 4 DEG C of refrigerators after deionized water dialysis 3~4d.
(2) preparation of micropin layer: by little molecule silk fibroin protein solution that concentration is 0.09g/mL by 4.5mg
Every 15*15 array is cast in PDMS (polydimethylsiloxane) mould, in the vacuum more than 0.09MPa
Under the conditions of degree after vacuum outgas bubble, constant temperature and humidity (temperature: 40 DEG C, relative humidity: 75%) is dried 24h;
(3) loading of ibuprofen: medication ibuprofen of the powder of doses being caught a cold is dissolved in chloroform,
It is cast in the needle-like convex surfaces of the not yet demoulding in step (2), and evacuation, perseverance under the same terms again
Constant temperature and humidity is dried;
(4) pressure-sensitive adhesive coating and the preparation of backing layer: by a certain amount of pressure-sensitive adhesives in step (3)
The encapsulation micropin layer back side of medicine, and pressing last layer flexibility PE film, then by it from PDMS die surface
Take off, through suitable cutting.
Embodiment two
(1) preparation of little molecule silk fibroin solution: as 2000mL mass fraction be by the silkworm cocoon of 40g
The Na of 0.25%2CO3In solution, repeat to boil at 98~100 DEG C three times, each 30min, and with deionization
Water is cleaned.Fibroin after degumming drying is dissolved in 9.3M lithium-bromide solution by the bath raio of 1:10 at 60 DEG C,
It is concentrated into 0.09g/mL, as stand-by in 4 DEG C of refrigerators after deionized water dialysis 3~4d.
(2) preparation of micropin layer: by every by 7mg for little molecule silk fibroin protein solution that concentration is 0.09g/mL
15*15 array is cast in PDMS (polydimethylsiloxane) mould, at the vacuum bar more than 0.09MPa
Under part after vacuum outgas bubble, constant temperature and humidity (temperature: 25 DEG C, relative humidity: 65%) is dried 24h;
(3) loading of insulin: the powder hypoglycemic drug insulin of doses is dissolved in
The HCL-Tris buffer of pH=2.5~3.5, is cast in the needle-like convex surfaces of the not yet demoulding in step (2),
And evacuation, constant temperature and humidity drying under the same terms again;
(4) pressure-sensitive adhesive coating and the preparation of backing layer: by a certain amount of pressure-sensitive adhesives in step (3)
The encapsulation micropin layer back side of medicine, and pressing last layer flexibility PE film, then by it from PDMS die surface
Take off, through suitable cutting.
Embodiment three
(1) preparation of little molecule silk fibroin solution: as 40000mL mass fraction be by the silkworm cocoon of 800g
The Na of 0.25%2CO3In solution, repeat to boil at 98~100 DEG C three times, each 30min, and with deionization
Water is cleaned.Fibroin after degumming drying is dissolved in 9.3M lithium-bromide solution by the bath raio of 1:10 at 60 DEG C,
It is concentrated into 0.09g/mL, as stand-by in 4 DEG C of refrigerators after deionized water dialysis 3~4d.
(2) preparation of micropin layer: by little molecule silk fibroin protein solution that concentration is 0.09g/mL by 10.5mg
Every 15*15 array is cast in PDMS (polydimethylsiloxane) mould, in the vacuum more than 0.09MPa
Under the conditions of degree after vacuum outgas bubble, constant temperature and humidity (temperature: 15 DEG C, relative humidity: 25%) is dried 24h;
(3) loading of hyaluronic acid: the solid powdery beautifying drug hyaluronic acid of doses is dissolved in water, system
Become finite concentration aqueous solution, be cast in the needle-like convex surfaces of the not yet demoulding in step (2), and again in phase
Evacuation, constant temperature and humidity drying under the conditions of Tong;
(4) pressure-sensitive adhesive coating and the preparation of backing layer: by a certain amount of pressure-sensitive adhesives in step (3)
The encapsulation micropin layer back side of medicine, and pressing last layer flexibility PE film, then by it from PDMS die surface
Take off, through suitable cutting.
In sum, the fibroin albumen microneedle patch that the present invention proposes, have the advantage that (1) its needle-like is empty
The volume in chamber accounts for the 40-90% of needle-like projection volume, and drug loading is high;(2) material of micropin layer is fibroin albumen,
Excellent in mechanical performance under dry state, possesses enough intensity and thrusts skin, owing to its molecular weight is less than 100,000,
And pour into a mould in micropin layer under conditions of uniform temperature (15~40 DEG C) and relative humidity (25~75%), its
Rate of dissolution is high, and after touching body fluid after thrusting skin, micropin layer dissolves rapidly, so medicine touch body fluid and
Dissolving diffuses to inside epidermis, is suitable for needing quick release and blood pharmaceutical quantities to require bigger symptom;(3) use
Little molecule silk fibroin water solution cast under gentle processing conditions and drying and moulding, it is to avoid photochemistry etching,
The technological process of the complexity such as plating, microchannel cast and the use of equipment needed thereby thereof, processing conditions is gentle, profit
In keeping biopharmaceutical macromolecular drug activity, hollow-core construction forming method is simple, energy consumption is low, technology requirement is low,
Processing cost is low, more conducively large-scale production;(4) traditional glass, silicon dioxide, siliceous and golden is compared
The entity micropins such as genus, fibroin albumen microneedle patch is lower with zest to skin sensitization;(5) conventional hollow is compared
Micropin often needs the defects such as another band drug storage warehouse, pressure control device, and the present invention is by being directly encapsulated in medicine
The method of needle-like cavity, at the swelling controlled release drug of micropin layer and on the premise of keeping its biological activity, greatly
The empty micropin patch transdermal drug delivery system structure simplified, practicality is more preferable;(6) current medicine and micropin are compared
Layer base material is blended the solubility micropin of aftershaping, this system with needle-like cavity (account for needle-like projection volume 40%~
90%) mode of packaging medicine, it is to avoid blended micropin makes the micropin needle body after molding because drug ratios is excessive
The defect that needle body intensity that fault of construction too much causes is more weak, carrying drug ratio is higher;(7) medicine can be with solid
Or the mode of liquid is loaded in needle-like cavity, medicine carrying mode is more flexible;(8) multi-medicament can be loaded, join
Close the rapidly-soluble characteristic of micropin housing, be particularly suitable for blood drug level dose requirements and relatively greatly and require quickly to see
The drug percutaneous release of effect, such as ibuprofen, insulin, relieve the effect of alcohol enzyme etc., and range is wide.
The above is only the preferred embodiment of the present invention, is not limited to the present invention, it is noted that
For those skilled in the art, on the premise of without departing from the technology of the present invention principle, also
Can make some improvement and modification, these improve and modification also should be regarded as protection scope of the present invention.
Claims (7)
1. a fibroin albumen microneedle patch, it is characterised in that: include backing layer, micropin layer, bond the described back of the body
Lining and the pressure-sensitive adhesive coating of micropin layer, it is protruding that described micropin layer is provided with several evenly distributed needle-likes, institute
Being provided with needle-like cavity in stating needle-like projection, the volume of described needle-like cavity accounts for described needle-like projection volume
40-90%, is provided with medicine in described needle-like cavity, the material of described micropin layer is fibroin albumen, fibroin albumen
Molecular weight less than 100,000.
Fibroin albumen microneedle patch the most according to claim 1, it is characterised in that: the wall of described micropin layer
Thickness is 5-40 μm, and the adjacent spacing of described needle-like projection is 0.1-1mm, height is 200-400 μm, tip
Diameter is not more than 10 μm, half high diameter is not more than 50 μm.
Fibroin albumen microneedle patch the most according to claim 1, it is characterised in that: described medicine includes cloth
Ibuprofen, aspirin, albumen, polypeptide drug insulin, blood digestive enzyme, vaccine, immune protein,
Any one in growth hormone, hyaluronic acid, creotoxin.
Fibroin albumen microneedle patch the most according to claim 1, it is characterised in that: described pressure-sensitive adhesive coating
For waterproof pressure sensitive gel coating.
Fibroin albumen microneedle patch the most according to claim 1, it is characterised in that: the material of described backing layer
Matter is flexible nonwoven cloth or PUR film.
6., according to the preparation method of the fibroin albumen microneedle patch described in claim 1 to 5 any one, it is special
Levy and be: comprise the following steps:
1) preparation of little molecule silk fibroin solution: be the Na of 0.25% as mass fraction by silkworm cocoon2CO3Molten
In liquid, repeat to boil at 98~100 DEG C three times, each 30min, and be washed with deionized water clean, by degumming also
Fibroin after drying is dissolved in 9.3M lithium-bromide solution by the bath raio of 1:10 at 60 DEG C, is concentrated into after dialysis
0.09g/mL;
2) preparation of micropin layer: by little molecule silk fibroin protein solution that concentration is 0.09g/mL by 4.5~10.5mg
Every 15*15 array is cast in polydimethylsiloxane mould, true under the vacuum degree condition more than 0.09MPa
After empty de-bubbled, constant temperature and humidity, temperature: 15~40 DEG C, relative humidity: 25~75%, be dried 36h with
On;
3) loading of medicine: solid drugs is first dissolved in respective volatile good solvent, described good solvent bag
Include in water, ethanol, chloroform any one, wiring solution-forming, be applied in step 2) described in
Micropin layer surface, more evacuated, freeze-day with constant temperature etc., make medicine enter needle-like cavity inside and make solvent wave
Send out;Suspension, emulsion are filled: utilize the method for ultrasonic disperse uniformly to be divided by insoluble solid powder medicaments
Dissipate in volatile solvent, turbid liquid system more stable in making the short time, be applied in step 2)
Described micropin layer surface, more evacuated, freeze-day with constant temperature, make medicine enter needle-like cavity and make solvent wave
Send out;
4) preparation of pressure-sensitive adhesive coating and backing layer: by pressure-sensitive adhesives in step 3) described in encapsulation
The micropin layer back side of medicine, and backing layer in pressing, then it is taken off from polydimethylsiloxane die surface,
The most plastic through suitable cutting.
The preparation method of fibroin albumen microneedle patch the most according to claim 6, it is characterised in that: described
Step 3) in, the medicine of loading directly can also be filled with the state of pressed powder.
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CN106422045A (en) * | 2016-09-05 | 2017-02-22 | 中国科学院理化技术研究所 | Flexible slow-release microneedle patch and preparation method thereof |
CN106730308A (en) * | 2016-12-08 | 2017-05-31 | 卢欣旸 | A kind of fibroin albumen micropin of imitative mosquito mouthpart and preparation method thereof |
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WO2019195350A1 (en) * | 2018-04-03 | 2019-10-10 | Vaxess Technologies, Inc. | Microneedle comprising silk fibroin applied to a dissolvable base |
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CN113440471A (en) * | 2021-05-20 | 2021-09-28 | 康迈丽德(深圳)生物科技有限公司 | Polymer microneedle and preparation method thereof |
WO2023004941A1 (en) * | 2021-07-30 | 2023-02-02 | 苏州大学 | Silk fibroin microneedle transdermal patch for treating insomnia and preparation method therefor |
CN116509768A (en) * | 2023-04-24 | 2023-08-01 | 广东瀚润生物科技有限公司 | Nanometer microneedle cosmetic with antioxidant and anti-wrinkle effects based on pure natural Chinese herbal medicine and silk extraction and preparation process thereof |
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