CN1541724A

CN1541724A - Fine stitch array for medicine controlled releasing

Info

Publication number: CN1541724A
Application number: CNA2003101084650A
Authority: CN
Inventors: 新傅; 傅新; 谢海波; 焦峰
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2003-11-04
Filing date: 2003-11-04
Publication date: 2004-11-03

Abstract

The mini needle array for controlling release of medicine includes one base board with slot in the bottom and one array of homogeneously distributed conic hollow mini needles, each of which is provided with eccentric hole in the tip and communicated with the slot in the base board. The mini needle array is manufactured via DIRE technological process to etch silicon. It is used for injection and has great hole depth/width ratio, sharp needle tip, moderate length, less destruction to skin, high medicine conveying efficiency, no pain produced and low infection probability.

Description

A kind of microneedle array that is used for medicine controlled releasing

Affiliated technical field

The present invention relates to controlled drug delivery devices, specially refer to a kind of microneedle array that is used for medicine controlled releasing.

Background technology

The major obstacle that drug transdermal absorbs is from the horny layer of human skin, and about 10～15 μ m are thick.Traditional drug administration by injection, syringe needle want transdermal to enter into deep tissues could effectively carry medicine, but causes infection and pain easily, especially some are avoided oral, dosage is little, needs the medicine of frequent injection, and traditional drug administration by injection more and more demonstrates its limitation.How could be high efficiency, accurately, in the body that conducts drugs to the people of no pain, become the focus of domestic and international research in recent years.Micropin is one of focus of wherein studying.The processing of micropin is to be support with the MEMS micro fabrication, adopts crystalline silicon, polymer, metal etc. as stock.Syringe needle can sting horny layer and enter the epidermal area depths and touch nerve less than the skin corium tissue, make the imperceptible pain of patient, and pin hole is little, and is little to the destructiveness of skin, reduced infected probability.

Selecting the material and the processing technique of micropin is the key of making microneedle array.At present, the various materials that are used for the micropin making mainly comprise silicon, metal and PMMA polymer, corresponding array process technology mainly comprises DRIE (Deep Reactive Ion Etching), LIGA (abbreviation of German Lithographic GalvanoformingAbforming, the meaning are photoetching, electroforming, mould casting), DEM (the little New Machining Technology of non-silicon 3 D, wherein the deep layer etching represented respectively in D, E, three letters of M, little electroforming, little english abbreviation that duplicates) etc. technology.Silicon then is the main material of making microneedle array at present.But, improve the performance of the easy brittle failure of silicon because the easy brittle failure of silicon can add some materials in addition and make synthetic " silicon ".The other metal, because its ductility is better with than being easier in micro structure trussell or plating, as palladium, nickel etc. also are used to make the material of micropin.

Summary of the invention

Purpose of the present invention provides a kind of microneedle array that is used for medicine controlled releasing, satisfies the actual needs of micropin administration, for the patient brings convenience and reduces misery.

In order to achieve the above object, the technical solution used in the present invention is as follows: open the microneedle array of being made up of one group of conical hollow micropin that is equally spaced on the slotted substrate in the bottom surface, in a side of syringe needle, the micropin pin hole is connected with the groove of substrate bottom surface the micropin pin hole partially.

The length of said conical hollow micropin is 100～150 μ m, and awl end external diameter is 50～80 μ m, and micropin pin hole internal diameter is 10～40 μ m, and micropin pin hole pin hole length is 80～100 μ m, and the micropin pin spacing is 100～120 μ m.

The material of substrate is silicon or metal or PMMA polymer.

The present invention compares with background technology, and the useful effect that has is:

1, syringe needle is sharp, can pierce through horny layer, and micropin is in thorn during transdermal, and the side has pressure, makes micropin disturb song and may be fractureed, so material has enough intensity to bear these pressure;

2, have higher depth-to-width ratio and array structure, because skin properties have an individual variation, and the distribution of blood capillary is at random, therefore needs certain transmission area to guarantee the effectiveness of medicine controlled releasing, adopts array structure can guarantee the transfer efficiency of medicine simultaneously;

3, the area of each punctures skin is little, to reduce the destructiveness to skin, reduces infected probability.Utilize present micro fabrication, the syringe needle diameter can be accomplished tens microns.

Description of drawings

Fig. 1 is a structural representation of the present invention;

Fig. 2 is the profile that amplify in Figure 1A zone;

Fig. 3 is the sketch map that microneedle array thrusts skin.

The specific embodiment

As shown in Figure 1 and Figure 2, the present invention it comprise:

Have the microneedle array of being made up of one group of conical hollow micropin 1 that is equally spaced on the substrate 2 of groove 4 in the bottom surface, in a side of syringe needle, the micropin pin hole is connected with the groove 4 of substrate bottom surface the micropin pin hole partially.

The length L of said conical hollow micropin 1 is 100～150 μ m, and awl end outer diameter D is 50～80 μ m, and micropin pin hole inner diameter d is 10～40 μ m, and micropin pin hole pin hole length 1 is 80～100 μ m, and micropin 1 pin spacing S is 100～120 μ m.

The present invention is used for the processing method of a kind of microneedle array of medicine controlled releasing:

1) silicon chip is carried out oxidation processes, generate the layer of silicon dioxide oxide-film, then to silicon chip cleaning, drying;

2) on the silicon chip one side, get rid of the last layer photoresist, aim at the mask plate that is furnished with the pinhole array pattern then, fix, under UV light, expose;

3) silicon chip of the light that exposed to the sun is put in the developer solution soaks, will dissolve because of the photoresist that qualitative change takes place in exposure, reuse acetone washes the photoresist that remains on the silicon chip;

4) remove the silicon dioxide oxide-film of exposure with fluohydric acid gas, it is clean to be put in DI (didymium) water rinsing;

5) silicon crystal that comes etching to expose with DRIE (Deep Reactive Ion Etching) etching technics is accurately controlled DRIE speed of etching and degree, can obtain the higher pinhole arrangement of depth-to-width ratio;

6) another side at silicon chip gets rid of the last layer photoresist again, aims at the mask plate that the cutting stylus head is used then, is put into exposure under the UV light, repeats the operating procedure of front, just can carve the needle array of marshalling.

This microneedle array is not a complete device, and an element of controlled drug delivery devices just, the function that play and puncture horny layer, is beneficial to drug conveying, and transfer efficiency height not only, and analgesia is arranged, few advantage that infects.During concrete the application, can carve a groove, be convenient to the storage of medicine,, also be convenient to encapsulation perhaps as the interface that is connected with miscellaneous part at the back side of substrate.

As shown in Figure 3, the invention provides a kind of typical microneedle array that meets the demands, a kind of conical hollow pinhead, material selection silicon, syringe needle is tapered, pin hole off-centre, keeping syringe needle can make pin sharper, easier thorn transdermal, and can when thrusting skin, can reduce obstruction to pin hole, make drug flow logical more smooth.Human anatomy shows that horny layer 5 thickness of skin are greatly about 15～20 μ m, and the thickness of horny layer 5 following table cortexes 6 does not still wherein contain blood vessel and nerve at 50～100 μ m.Pin about length 150 μ m just can penetrate horny layer 5, reaches epidermis inside, and stimulates the nerve less than skin corium 7, and making whole injection process is all to be painless.

Claims

1, a kind of microneedle array that is used for medicine controlled releasing, it is characterized in that it comprises: the substrate (2) that has groove (4) in the bottom surface is gone up the microneedle array of being made up of one group of conical hollow micropin (1) that is equally spaced, in a side of syringe needle, the micropin pin hole is connected with the groove (4) of substrate bottom surface the micropin pin hole partially.

2, a kind of microneedle array that is used for medicine controlled releasing according to claim 1, it is characterized in that: the length (L) of said conical hollow micropin (1) is 100～150 μ m, awl end external diameter (D) is 50～80 μ m, micropin pin hole internal diameter (d) is 10～40 μ m, micropin pin hole pin hole length (1) is 80～100 μ m, and micropin (1) pin spacing (S) is 100～120 μ m.

3, according to claim 1 or described a kind of microneedle array that is used for medicine controlled releasing, it is characterized in that: the material of substrate (2) is silicon or metal or PMMA polymer.