CN104667420B - Transdermal drug delivery device - Google Patents

Abstract

A kind of transdermal drug delivery device, which is included in default pattern, to be pierced through patient skin (4) to form the pin (46 in hole (44), 62), and the carrier (40,82) of the medicine (42) for loading conveying in same pattern.There is provided and work as pin (46,62) carrier (40,82) is loaded into the component in hole (44) medicine (42) is transported to the position below skin (4) surface by hole (44) when resting on skin (4).

Description

Transdermal drug delivery device

Technical field

The present invention relates to the field that transdermal delivery medicine enters patient body, more particularly to by being manufactured in advance on skin Hole convey medicine field.

For the sake of brief introduction, the term " medicine " used in this specification may need to be introduced in patient suitable for any Body is to provide treatment, beauty or the biological active agents of nutritive validity.The patient can be the mankind's either non-human Animal.It is " transdermal " be applied to by the conveying of the skin of patient or by other enterable surface texture such as corneas or The conveying of cavity interior.

Background technology

By using gradually move micropin contact skin device come strengthen skin penetration of drugs effect method by Description, such as by directly in roller bearing formation microneedle array, or as described in international patent application WO2008/125798, By forming microneedle array being fixed on the cover plate of the band run on one group of roller bearing.This method has been proved to than simply Plane microneedle array is pressed onto skin first-class.This is due to need smaller insertion force and due to consideration that pin array is a line one Insert capablely, the repeatability of pharmaceutical quantities independently increases with operator.

Major obstacle by dermal delivery of drugs is cuticula, and the cuticula is tough and tensile dead skin cells outer layer.This is micro- Pin can be hollow, and liquid medicine is conveyed to provide passage by the cuticula, or they can be solid and letter Singly scribble the medicine to be conveyed.Alternatively, a device for including solid micropin can be used for destruction cuticula and/or for making The hole through the cuticula is made, to improve it to medicine that skin surface is then for example applied in the form of gel or patch The permeability of thing.However, because pin only penetrates the sub-fraction of treated skin surface area, most of medicine being then applied in Composition formula does not enter into inside hole and is retained in the surface of skin.This application corresponding with most drug legislation responsible institutions is most The requirement of few medication amount on the contrary, and minimum surplus must be introduced after application.It is also simultaneously to potential expensive product Waste.

The content of the invention

The present invention provides a kind of transdermal drug delivery device as defined in claim 1, preferably but it is non-essential Feature is defined in dependent claims.

By only conveying medicine to the position in the hole being previously formed, the quantity of controlled pharmaceutical formulation can be exactly by The hole for penetrating the cuticula is transported to place that it can pass through and can be absorbed by the body.Stay in skin surface and body can not be reached The drug loss of body is by minimum.The medicine can be transported to the aperture, particularly if the medicine is when being in liquid condition.It is excellent Selection of land, the medicine is directly positioned into the hole by the carrier.As other transdermal delivery therapies, the medicine can be from the cuticula Spread, and scattered by body below.It is applied to the pharmaceutical formulation of various states, including solid-state (powder or particulate) medicine Thing.

Simplest component for forming multiple holes on skin includes multiple pins.Shared mechanical device can be then For pilot pin and pharmaceutical carrier to ensure the consistent arrangement between them.But other machinery or non-mechanical component such as Laser ablation component can be used on position predetermined on skin forming hole.

Brief description of the drawings

Fig. 1 a and 1b convey two steps of the medicine to the method for patient for first embodiment of the invention with device；

Fig. 2 a and 2b convey two steps of the medicine to the method for patient for second embodiment of the invention with device；

Fig. 3 a and 3d convey four steps of the medicine to the method for patient for third embodiment of the invention with device；

Fig. 4 a and 4c convey three steps of the medicine to the method for patient for fourth embodiment of the invention with device.

Embodiment

Fig. 1 a and 1b are the schematic diagram of the transdermal drug delivery device with framework 2.The framework 2 is maintained at a patient The fixed position of skin treatment area.Axle 6 extends between the opposite side of framework 2 in the direction for being substantially parallel to skin surface.Should Axle transports the block 8 for the array that there is one side the array and reverse side of micropin 10 to have micro-structural 12.Two arrays 10,12 have phase Same layout.In a side elevational view in fig. 1, only the single file of micropin 10 and the single file of micro-structural 12 are visible, but actually Each array extends on the two dimensional surface of block 8.

Any suitable method such as shaping or micro Process can be used to be formed for the micropin 10.They can have one from tens Micron is usually several times of length to the diameter more than one millimeter of scope and more than their width.The length is preferably worn enough The cuticula of transdermal but being not more than can allow the pin to reach the length of nerve endings more deeper than skin.

The micro-structural 12 is preferably long part such as bar or post.Different from traditional micropin, the micropin is formed with blunt tip. The tip is preferably flat, that is to say, that be generally plane and perpendicular to the major axis of the micro-structural 12.The micro-structural 12 with The micropin is similar, can by any suitable type plastics, ceramics or metal manufacture, and need to have allow insertion medicine it is direct Into the size and dimension in the hole created by micropin.In order to realize that this target micro-assembly robot may remain in more than cuticula, Purely play a part of to force the drug through the hole, or it may be configured such that it can penetrate the hole manufactured by the micropin Directly to convey the medicine deeper region into the skin.The micro-structural is therefore small than the hole that is created by micropin to allow it Skin is inserted to make it force the drug through skin；Or it can be inclined or be chamfered so that although the micro-structural Bigger than the hole of establishment or bigger than the pin for being used to create hole, it is still that can penetrate the hole and medicine is forced into skin more Depths.

The medicine of any Suitable formulations can be on the tip of the micro-structural 12., should if the formula is solid form One or more particle 14 of formula can be attached on the tip by using the adhesive that can not dissolve the particle.It is optional The ground particle 14 can be avoided by electrostatic adherence using any degeneration that may cause particle in storing process or weakening Adhesive.The tip that electrostatic charge will be concentrated to the tip of the carrier and the particle 14 can be promoted to be attached to the carrier.Utilize magnetic The particle of gravitation Metal Substrate can be installed in the tip of the micro-structural.

The often end of the axle of delivery device is installed in mechanism 16, and the mechanism allows skin of the axle towards patient 4 movements or the remote skin.As shown in the double-head arrow 18 in Fig. 1 a and Fig. 1 b, the motion towards the skin can be by manually pressing Power is completed.The motion can be guided by groove (not shown), and can provide back-moving spring (not shown) to retract Axle 6 returns to its initial position away from skin 4.It is purely schematical to be appreciated that accompanying drawing.In practice, it is necessary to which top is provided Lid towards micropin 10 or micro-structural 12 prevents the unexpected contact of user.One, which can be provided, ensures the machine of the holding level of axle 6 Structure.Axle 6 automatically rather than can be manually completed toward and away from the motion of the skin, and can be provided adjustment and impacted skin The component of the power of skin 4.

This " punching press " action is performed with the micropin 10 in face of skin 4 first, as shown in Figure 1a, to pierce through cuticula, and is created Build hole array 20 as shown in Figure 1 b.Then block 2 rotates 180 degree around axle 6, as shown in curved arrow 22, therefore micro-structural 12 Skin 4 is faced now, and it is perfectly aligned with preformed hole 20.Then same punching press is repeated to act so that micro-structural 12 is entered Enter respective hole 20 and each micro-structural places the medicine 14 of its load to the desired depth in hole 20.

Block 8 is not limited to single microneedle array 10 and the single micro-structural for being separated by 180 degree with microneedle array.It is probably many The individual angled array being distributed in as the face of the surface of cylinder or prism.Then indexing unit can be provided by block 8 Manually or automatically by an appropriate angle, to ensure block 8 with required array type being accurately positioned towards skin 4. By this way, the medicine of more than one type can be fed sequentially into single group hole 20.

Assuming that they are fully accurately positioned, microneedle array 10 and micro structure array 12 can be formed with single patch To be attached on the surface of block 8.Alternatively, microneedle array 10 and micro structure array 12 can be along the belts for being wrapped in cylinder block 8 The surface of (not shown) is arranged alternately, and belt is promoted with the component of the cylinder is rotated by a predetermined distance and is incited somebody to action One array takes correct position to.

Fig. 2 a and 2b are the schematic diagrames of another transdermal drug delivery device, in the apparatus, for exchanging microneedle array 10 and the component of micro structure array 12 be related to rotation around the axle 30 for being essentially perpendicular to skin 4, as shown in curved arrow 32.There is provided Component (not shown in detail) is to allow left array (as shown in the drawing) to touch skin 4 and be then withdrawn, with above institute Punching press action is stated similar, as shown in double-head arrow 34.First, microneedle array 10 is pushed into skin 4 and retracts to form hole 36.So Afterwards, the equipment rotates around its axle 30 and takes the micro structure array 12 for carrying drug particles 14 to overlapped with hole 36 local and again Multiple punching press acts to convey medicine access aperture 36.

Axle 30 can also be configured to flexible extruding to drive left array to be contacted with skin, (not shown with return spring Go out) array is gone back to return to its initial position.If skin is flat, such setting often allows right array simultaneously Another different zones of skin are contacted, this has to be avoided.Can provide shield the skin area component or the equipment can To be arranged to right array higher than left array, the angle for for example adjusting axle 30 makes it be slightly away from vertically, while by the work on the left side Dynamic array remains parallel to the surface of skin.Not exclusively the position of exchanging array is capable of in rotary motion.The device of the present invention can Microneedle array 10 is skidded off position and micro structure array 12 is slipped into position, it is preferable that both are in same motion.

Fig. 3 a to Fig. 3 d show the delivery device of different embodiments of the invention, in the delivery device, when The micropin 46 in hole 44 is formed still on skin, medicine 42 is incorporated into hole 44 by the microstructure.These figures show single pin, this It is other parts that are typical but being not precluded from the array with same needle.Fig. 3 a show the micropin on patient skin 46.Pharmaceutical formulation particle 42 is attached to its flat tip 48 by micro-structural 40.(medicine is that graininess or even solid-state right and wrong must Want.) micro-structural 40 be in retracted position thus micropin 46 can penetrate the surface of skin 4 and medicine 42 is not contacted with skin, such as Shown in Fig. 3 b.The hole 44 that the formation of micropin 46 passes through the outer layer of skin 4.

Next, the retracted position of micro-structural 40 as shown in Figure 3 b is proceeded in deployed position as shown in Figure 3 c, along pin 46 surface is walked and entered the hole 44 formed by pin.The medicine can be placed to this from the flat tip of micro-structural A suitable depth is can be absorbed by the patient in hole 44.As shown in Figure 3 d, micropin 46 and micro-structural 40 then can be simultaneously Recalled from skin, close hole rapidly like that and leave embedded medicine 42.

In Fig. 3 a to 3d embodiment, micropin needs not be cylinder or cone, but can have one it is flat Cross section or approximate wedge shape are to be presented one or more flat sides.This provide the microstructure 40 can bear compared with Large surface.The side of micropin can also be provided with least one cannelure, and the cannelure provides space to accommodate medicine in hole 44 Thing and excite medicine to flow down the groove to enter skin deeper inside.Fig. 4 a to 4c illustrate the handheld apparatus of yet another embodiment of the invention Schematic cross-sectional.The device includes a shell 50, and it is formed by two parts, i.e. top 51 and bottom 52.Top 51 is with Portion 52 is engaged with each other, so as to sliding relative movement (as shown in the figure) in vertical direction.As will be discussed below, the fortune Move by compression spring control.The lower surface 54 of the general planar of bottom 52 is used to lean against patient's skin during the equipment is used On skin.The upper surface 56 on top 51 is used to be pressed by the hand of user, and can be generally flat or bending, extra to provide It is comfortable or control.The cavity 57 that the top 51 and bottom 52 of shell are formed between them.Cam face 58 is from top 51 Inwall is projected into cavity 57.

Central opening is formed in the lower surface 54 of shell, so that the central opening can receive disposable blade 60. Component such as hook or clip (not shown), insert is fixed, then can release manually in a device in use Put to allow insert 60 to carry out demolition and replacement.When fixing in a device, except single file pin 62 be installed in insert and The tip of pin is protruded from so that they can penetrate the outer layer of the skin of patient immediately below lower surface 54, and insert 60 is fully located at outer In shell border.(hand-manipulating of needle 62 extends perpendicularly into Fig. 4 a-4c plane, so only one of which is visible.If defeated The medicine sent is highly effective, can only need to single pin, rather than row's pin).

Two parts are formed insert 60 again, i.e. top 64 and bottom 66.Upper and lower part 64,66 is engaged with each other, so as to energy Enough sliding relative movement (as shown in the figure) in vertical direction.Bolt 68 positioned at the upper surface of insert bottom 66 is inserted with being located at The recess 70 of the lower surface on part top 64 aligns.Bolt 68 and recess 70 provide position to the first compression spring 72.(it may be appreciated It is that the position of bolt 68 and recess 70 can be exchanged, or the component of springs 72 can be laid using other.)

One group of inclined passage 74 is formed with insert 60.One passage 74 corresponds to a pin 62.Each passage 74 Including be formed at insert top 64 upper channel 76 and be formed at the lower channel 78 of insert bottom 66.Each lower channel 78 with The lower surface 80 of insert 60 intersects at the local close point occurred with corresponding pin 62.Long pharmaceutical carrier 82 is located at every In individual upper channel 76.The tip 84 of carrier substantially takes up the whole cross section of passage 76.The upper end 86 of carrier is from insert 60 It is projected into the cavity 57 of upper shell 51.As illustrated, upper end 86 can be wider than tip so that provide can easily applying power Surface.Under the influence of the power, carrier 82 can be slided along upper channel 76.

Bolt 88 positioned at the upper surface on the top 64 of insert gives the second compression spring 90 offer position, the second compression bullet Spring 90 is acted between the inwall on the top 51 of insert 60 and shell body 50.Second spring 90 can be arranged at lid center dant (not shown), and it is understandable that the position of bolt 88 and optional recess can exchange or can use other Lay the component of spring 90.

Fig. 4 a show the original state of the device, when first and second compression spring 72,90 is prolonged to greatest extent It is long.The top 51 of shell body 50 is separated with bottom 52.The top 64 of insert 60 is separated with bottom 66, final each passage Do not alignd with lower part 78 on 74 top 76.Carrier 82 is recalled from the part of upper channel 76, therefore sky is stretched into the upper end 86 of carrier Chamber 57 is simultaneously approached or engaged with cam face 58.One medicine (not shown) is loaded into each upper channel 76 and is contained in medicine The tip 84 of the front end of carrier 82 wall 92 relative with the bottom 66 of insert, therefore in transport and storage process, medicine without Method is spilt from insert 60.

Will the equipment convey medicine to patient, manual pressure is applied to the face 56 at the top of shell body 50.Pin 62 can be made Penetrate the outer surface of patient skin and form the hole of medicine entrance.First compression spring 72 is to be weaker than the second compression spring 90, institute With as shown in Fig. 4 b, as long as what Manual pressure continued to be compressed first is the first compression spring 72.This allows insert 60 Top 64 and bottom 66 contact, and the top 76 and bottom 78 of ramp way 74 is in alignment with each other, release has accommodated upper channel 76 medicine is flowed into lower passage 78.

Because extra pressure is applied in the face 56 at the top of shell body 50, the top 64 of insert 60 and bottom 66 connect Closing prevents 2 further compressions of the first compression spring 7, so the second compression spring 90 then starts compression.This allows shell body 50 top 51 is towards mobile bottom 52.In doing so, cam face 58 starts to resist the upper end 86 of pharmaceutical carrier 82, and forces Each carrier 82 is slided along upper channel 74, and in piston mode therefrom into the discharge medicine of lower channel 78.Under lower channel 78 End is existing to be alignd with the hole formed by pin 62, therefore medicine is directly conveyed the hole, the skin that medicine passes through the patient in the Kong Zhongneng Skin.

Construction shown in Fig. 4 c, when second spring 90 is compressed to greatest extent, pharmaceutical carrier 82 has been driven fully into logical The top 51 of road 74 and shell body 50 with lower bond.Hook (not shown) can be provided to be made with retainer member With rear in the construction compressed completely, so the device is using being it will be apparent that being replaced by new one in insert 60 Before agent medicine, it will not make and reuse its trial.

It is worth noting that, in this embodiment of the invention, because the position of medicine is controlled by passage 74, medicine does not have There is the tip 84 that is adhered to carrier.Therefore, the medicine is optionally fluid form.In addition, the tip 84 of carrier is not Being must be in the extreme close to the hole of the association in skin, as long as it fully shifts the medicine before it onto hole.

Although pin 62 is shown as fixed on insert 60, and is for good and all extended from its bottom surface 80, it can carry For the sophisticated of the pin 62 for shielding or for pin being shunk in always inside insert 60 until device is already prepared to use Component.Then when pressure is applied in the face 56 at the top of shell body 50, the pin of the retraction can be manually or automatically Extension.For example, pin may be mounted at the top 64 of insert 60, and through the guide rail of bottom 66.Then, upper and lower part 64,66 move together, change to Fig. 4 b constructions from Fig. 4 a construction, syringe needle will move along guide rail, until their tip is the bottom of from Protrude in face 80.

Claims (8)

1. a kind of transdermal drug delivery device, including：

It is used to pierce through the pin (46,62) of the skin (4) of patient to form the structure of multiple holes (44) on the skin (4) including multiple Part；

Multiple carriers (40,82), each carrier is the long part with the tip (84) for loading the medicine to be conveyed (42)； And

It is exercisable when the pin (46,62) rests on skin (4), for by each carrier (40,82) be loaded into hole (44) with Medicine (42) is transported to the component in the hole (44)；

It is characterized in that：Each carrier (40) is positioned so that the carrier (40) is introduced in beside corresponding pin (46) Hole (44).

2. a kind of transdermal drug delivery device as claimed in claim 1, it is characterised in that also including be loaded into carrier (40, 82) medicine (42) at tip (84).

3. a kind of transdermal drug delivery device as claimed in claim 2, it is characterised in that the medicine (42) adheres to the carrier (40,82) tip (84).

4. a kind of transdermal drug delivery device as claimed in claim 1, it is characterised in that each of carrier (40,82) can Slided relative to a corresponding pin in multiple pins (46,62).

5. a kind of transdermal drug delivery device as claimed in claim 4, it is characterised in that also including related to each carrier Passage, the carrier can be slided along the passage.

6. a kind of transdermal drug delivery device as claimed in claim 5, it is characterised in that the passage is located at the corresponding pin (46) it is inner.

7. a kind of transdermal drug delivery device as described in any one of claim 1-6, it is characterised in that each carrier (40,82) tip is blunt.

8. a kind of transdermal drug delivery device as described in any one of claim 1-6, it is characterised in that each carrier (40,82) it is bar, mark post or piston.