CN115006709A - A kind of bionic microneedle and its manufacturing method - Google Patents

Abstract

The invention relates to the technical field of medical instruments, in particular to a bionic microneedle and a manufacturing method thereof. Bionic micropin includes the micropin needle body, two at least slots have been seted up to the surface of micropin needle body, constitute the arris ridge between the adjacent slot, the slot is followed the length direction of micropin needle body extends, and this bionic micropin can pierce hyperkeratosis skin under less thrust, effectively reduces or eliminates micropin bending and fracture phenomenon to have that the medicine-carrying capacity is big, used repeatedly and to the little advantage of skin injury. The bionic microneedle is manufactured by a 3D printing technology and has the advantage of quick forming.

Description

A kind of bionic microneedle and its manufacturing method

technical field

The invention relates to the technical field of medical devices, in particular to a bionic microneedle and a manufacturing method thereof.

Background technique

Hyperkeratotic skin diseases such as viral warts, tinea pedis, and psoriasis manifest as skin thickening. The common treatment method is to apply cream to the affected area. However, due to the existence of the stratum corneum, topical cream is applied to the skin surface. 10% to 20% or less of the drug contained in the cream can be absorbed through the skin, and hyperkeratotic skin can further hinder the penetration of the drug and reduce the utilization of the drug.

As a new type of transdermal drug delivery carrier, microneedles can directly deliver drugs to the epidermis or upper dermis with fewer nerves by penetrating the stratum corneum barrier, so that the drugs can reach the treatment site and exert their curative effect, which can effectively improve the efficacy of the drugs. utilization. Microneedles are currently used to treat psoriasis and viral warts, delivering drugs directly to the affected area and enhancing drug penetration. Studies have shown that poking with polymer solid microneedles can enhance methotrexate delivery in pig and human cadaver skin, and bleomycin-coated polylactic acid solid microneedles have been used to treat viral warts, using microneedles The advantages of treating hyperkeratotic skin diseases are that it can improve the drug absorption rate, reduce the toxic and side effects of injection or oral administration, high patient compliance, and convenient use.

However, when the existing microneedle structures such as cylindrical microneedles penetrate into hyperkeratotic skin, due to the hardness of the hyperkeratotic skin, the penetration force of the microneedles will become larger and the penetration of the microneedles will be difficult, and the microneedles are prone to breakage and bending, and at the same time, the The specific surface area of the microneedles is small, and the drug load coated on the surface of the microneedles is small, so effective treatment cannot be performed.

Chinese Patent No. 202010726931.5 discloses a bionic microneedle patch for transdermal drug delivery. The microneedle is designed with a barbed bionic structure. Although the patented technology can prevent the microneedle from breaking, when the barbed bionic structure is pulled out It will hook the skin, the barbs will be destroyed and can only be used once, and when the barbs are pulled out, the skin will be hooked and the skin will cause great pain.

SUMMARY OF THE INVENTION

One of the objectives of the present invention is to avoid the deficiencies in the prior art and provide a bionic microneedle, which can penetrate the hyperkeratotic skin with a relatively small thrust, thereby effectively reducing or eliminating the microneedle Bending and breaking phenomenon; and, the bionic microneedle has the advantages of large drug loading, reusability and less damage to the skin.

The second purpose of the present invention is to provide a method for manufacturing a bionic microneedle.

For achieving one of the above-mentioned purposes, the present invention provides the following technical solutions:

A bionic microneedle is provided, comprising a microneedle needle body, at least two grooves are formed on the outer surface of the microneedle needle body, ridges are formed between adjacent grooves, and the grooves are along the microneedle needle. The length of the body extends.

In some embodiments, the microneedle body is in the shape of a vertebral body, the groove extends along the outer side of the vertebral body, and the width of the groove gradually expands from the top of the vertebral body to the bottom of the vertebral body .

In some embodiments, the height of the vertebral body is 100 μm˜2000 μm, and the bottom diameter of the vertebral body is 100 μm˜1000 μm.

In some embodiments, the groove includes a first end and a second end, the first end extends to the bottom of the vertebral body, the width of the first end is 10 μm˜100 μm, and the second end Extending to the top of the vertebral body, the width of the second end is 1 μm˜10 μm; the depth of the groove is 1 μm˜20 μm.

In some embodiments, there are several microneedle bodies, the several microneedle bodies are arranged on the base in a matrix, one end of the microneedle bodies is fixed on the base, and the other end is a needle tip and faces away from the substrate.

The beneficial effects of a bionic microneedle of the present invention:

(1) In the bionic microneedle of the present invention, a groove is provided on the microneedle needle body, the groove extends along the length direction of the microneedle, and the microneedle needle body forms both grooves and ridges, The grooves play a drag-reducing role, and the grooves are arranged on the microneedle body, so that the microneedles can penetrate the skin with less thrust, reducing or eliminating the bending and breaking of the microneedles. In addition, the ridges of the microneedle body maintain the strength of the microneedle body, and further reduce or eliminate the phenomenon of bending and breaking of the microneedle.

(2) The bionic microneedle of the present invention has a groove on the microneedle body, which increases the surface area of the microneedle, more medicines are coated on the surface of the microneedle, and effectively improves the drug load of the microneedle, Microneedling is used in the treatment of hyperkeratotic skin diseases, which can promote the permeability of drugs in the skin and improve the efficiency of drug transdermal absorption.

(3) In the bionic microneedle of the present invention, the groove extends along the length direction of the microneedle. When the microneedle is pulled out, the groove and the ridge move along the direction of pulling out, and the bionic part of the microneedle body does not move. By hooking the skin, the bionic part of the microneedle body will not be damaged, making the microneedle body reusable, and avoiding the problem of pain caused by the traditional bionic microneedle being hooked on the skin, which is suitable for mass production applications.

In order to achieve the second objective of the present invention, a multi-layer microneedle is provided, which is prepared by the above-mentioned bionic microneedle.

In some embodiments, the multi-layer microneedles are bilayer microneedles.

Description of drawings

Fig. 1 is the structural schematic diagram of the bionic microneedle of the present embodiment 1;

Fig. 2 is the structural schematic diagram of the bionic microneedle patch of the present embodiment 1;

3 is a topography diagram of the bionic microneedle of the present embodiment 1, wherein, figure a is an optical diagram of the bionic microneedle, figure b is a top view of the bionic microneedle helium ion microscope, and figure c is a side view of the bionic microneedle helium ion microscope;

Fig. 4 is the mechanical property curve diagram of the bionic microneedle of the present embodiment 1 piercing the mouse skin;

Figure 5 is a graph showing the mechanical properties of traditional microneedles pierced into mouse skin without biomimetic structures.

reference number

Microneedle body 1; groove 2; ridge 3; base 4.

Detailed ways

Preferred embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While preferred embodiments of the present invention are shown in the drawings, it should be understood that the present invention may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the present invention to those skilled in the art.

The terminology used in the present invention is for the purpose of describing particular embodiments only and is not intended to limit the present invention. As used herein and in the appended claims, the singular forms "a," "the," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It will also be understood that the term "and/or" as used herein refers to and includes any and all possible combinations of one or more of the associated listed items.

It should be understood that although the terms "first", "second", "third", etc. may be used in the present invention to describe various information, such information should not be limited by these terms. These terms are only used to distinguish the same type of information from each other. For example, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information, without departing from the scope of the present invention. Thus, a feature defined as "first" or "second" may expressly or implicitly include one or more of that feature. In the description of the present invention, "plurality" means two or more, unless otherwise expressly and specifically defined.

Example 1

When the existing microneedle structures such as cylindrical microneedles penetrate into hyperkeratotic skin, due to the hardness of the hyperkeratotic skin, the penetration force of the microneedle will become larger and the penetration of the microneedle will be difficult, and the microneedle is prone to breakage and bending. The specific surface area of the needle is small, and the drug load coated on the surface of the microneedle is small, which cannot be effectively treated. Although the prior art discloses a bionic microneedle patch for transdermal drug delivery, the barb bionic structure will hook the skin when it is pulled out, and the barb will be damaged so that it can only be used once, and the barb will hook when pulled out. Sticking to the skin makes the skin more painful.

In order to solve the above problems, this embodiment provides a bionic microneedle, as shown in FIG. 1 , including a microneedle needle body 1, the outer surface of the microneedle needle body 1 is provided with at least two grooves 2, and the adjacent grooves 2 are formed. Ridges 3 are formed between them, and the grooves 2 extend along the length direction of the microneedle body 1 .

In the bionic microneedle of the present invention, a groove 2 is formed on the microneedle needle body 1, the groove 2 extends along the length direction of the microneedle, and the microneedle needle body 1 forms both the groove 2 and the rib. Ridge 3, since the groove 2 plays a role in reducing drag, a groove is arranged on the microneedle needle body, the microneedle can penetrate the skin with less thrust, and the phenomenon of bending and breaking of the microneedle is reduced or eliminated. The ridge 3 of the microneedle needle body 1 maintains the strength of the microneedle needle body 1, and further reduces or eliminates the phenomenon of bending and breaking of the microneedle. Groove 2 increases the surface area of the microneedles, and more drugs are coated on the surface of the microneedles, which effectively increases the drug load of the microneedles. The microneedles are used for the treatment of hyperkeratotic skin diseases and can promote the permeability of drugs in the skin , to improve the efficiency of drug transdermal absorption. When the microneedle is pulled out, the groove 2 and the ridge 3 move along the direction of pulling out, the bionic part of the microneedle body 1 will not hook the skin, and the bionic part of the microneedle body 1 will not be damaged, so that the The microneedle needle body 1 is reusable, and also avoids the problem that the skin of the traditional bionic microneedle is hooked and causes pain, and is suitable for mass production applications.

In this embodiment, the microneedle body 1 is in the shape of a vertebral body, the groove 2 extends along the outer side of the vertebral body, and the width of the groove 2 goes from the top of the vertebral body to the bottom of the vertebral body gradually expand.

The shape of the microneedle needle body 1 is a vertebral body, which is strong and easy to penetrate into the skin. The groove 2 becomes larger as the cross-section of the vertebral body becomes larger, and the groove 2 can be set to the greatest extent. The specific surface area of the microneedle needle body 1, and the penetration force of the microneedle needle body 1 is reduced.

Example 2

For ease of understanding, this embodiment provides another embodiment of the bionic microneedle. In practical applications, the height of the vertebral body is 100 μm to 2000 μm, preferably 800 μm, and the diameter of the bottom of the vertebral body is 100 μm to 1000 μm, preferably 260 μm . The height of the vertebral body and the bottom of the vertebral body can be directly selected according to actual needs, which are not limited here.

The groove 2 includes a first end and a second end, the first end extends to the bottom of the vertebral body, the width of the first end is 10 μm˜100 μm, preferably 40 μm, and the second end extends To the top of the vertebral body, the width of the second end is 1 μm˜10 μm, preferably 2 μm; the depth of the groove 2 is 1 μm˜20 μm, preferably 10 μm. The height of the vertebral body and the diameter of the bottom of the vertebral body can be selected according to actual needs, which are not limited here.

Example 3

For ease of understanding, this embodiment provides another embodiment of the bionic microneedle. In practical application, as shown in FIG. 2 , there are several microneedle needle bodies 1 , and the plurality of microneedle needle bodies 1 are arranged on the base 4 in a matrix. One end of the microneedle needle body 1 is fixed on the base 4 , and the other end is a needle tip and faces away from the base 4 .

A plurality of microneedle needle bodies 1 are arranged on the base 4 to obtain a microneedle patch, which is convenient to apply medicine to a certain area of skin at the same time. Exemplarily, the microneedle array is 4*5, and the microneedle patch is coated with methotrexate, and after drying, it is pierced into the surface of the psoriatic skin, and after being pulled out, the methotrexate continues to be coated on the acting site, The drugs used can be external drugs, such as vitamin D3 analogs, glucocorticoids, anthralin, tretinoin, immunosuppressants and other external drugs, and can also be internal drugs, such as methotrexate and antibiotics.

Example 4

This embodiment discloses a method for manufacturing a bionic microneedle, and the bionic microneedle described in Embodiment 1 is manufactured by 3D printing technology.

The 3D printing technology uses a laser to focus on the printing material, so that the printing material solidifies sequentially from point to line and from line to surface to complete the drawing operation of one level, and then the lifting table moves the height of one layer in the vertical direction, and then solidifies another layer. Layers and layers are superimposed to form a three-dimensional entity.

In this embodiment, the printing raw material includes a photosensitive resin, a reactive diluent and a photoinitiator. Photosensitive resin and reactive diluent are polymerized and cured with the participation of photoinitiator.

In this embodiment, the photoinitiator includes one or a mixture of any two or more of benzoin and its derivatives, acetophenone derivatives or triaryl thiobellate salts.

Effect verification:

1. Figure 3 is a topography diagram of the bionic microneedle of the present embodiment 1, wherein, Figure a is an optical diagram of the bionic microneedle, Figure b is a top view of the bionic microneedle helium ion microscope, and Figure c is the side of the bionic microneedle helium ion microscope. View; as can be seen from the figure, the microneedle is in the shape of a pyramid, and the outer surface of the microneedle needle body 1 is provided with six grooves 2, and ridges 3 are formed between adjacent grooves 2, and the grooves 2 are along the The length direction of the microneedle needle body 1 extends, and the present invention can obtain the microneedle imitating a cactus.

2. Fig. 4 is a graph showing the mechanical properties of the bionic microneedle in Example 1 pierced into the skin of a mouse, and Fig. 5 is a graph of the mechanical properties of a traditional microneedle without a bionic structure pierced into the skin of a mouse. The cone height and base diameter of the needles were the same as those of the microneedles in Figure 5. The first large inflection point in the curves of Figures 4 and 5 is the force with which the skin is pierced. It can be seen from the figure that the penetration force of the bionic microneedle of Example 1 into the skin is 0.013N, and the penetration force of the ordinary microneedle into the skin is 0.094N. It can be seen that the bionic microneedle of the present invention can penetrate the skin with a small penetration force. .

The relative arrangement of the components and steps, the numerical expressions and numerical values set forth in these embodiments do not limit the scope of the present application unless specifically stated otherwise. Meanwhile, it should be understood that, for the convenience of description, the dimensions of various parts shown in the accompanying drawings are not drawn in an actual proportional relationship. Techniques, methods, and devices known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the authorized description. In all examples shown and discussed herein, any specific value should be construed as illustrative only and not as limiting. Accordingly, other examples of exemplary embodiments may have different values. It should be noted that like numerals and letters refer to like items in the following figures, so once an item is defined in one figure, it does not require further discussion in subsequent figures.

In the description of this application, it should be understood that the orientations indicated by the orientation words such as "front, rear, top, bottom, left, right", "horizontal, vertical, vertical, horizontal" and "top, bottom" etc. Or the positional relationship is usually based on the orientation or positional relationship shown in the drawings, which is only for the convenience of describing the present application and simplifying the description, and these orientations do not indicate or imply the indicated device or element unless otherwise stated. It must have a specific orientation or be constructed and operated in a specific orientation, so it cannot be construed as a limitation on the protection scope of the application; the orientation words "inside and outside" refer to the inside and outside relative to the contour of each component itself.

For ease of description, spatially relative terms, such as "on", "over", "on the surface", "above", etc., may be used herein to describe what is shown in the figures. The spatial positional relationship of one device or feature shown to other devices or features. It should be understood that spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as "above" or "over" other devices or features would then be oriented "below" or "over" the other devices or features under other devices or constructions". Thus, the exemplary term "above" can encompass both an orientation of "above" and "below." The device may also be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptions used herein interpreted accordingly.

In addition, it should be noted that the use of words such as "first" and "second" to define components is only for the convenience of distinguishing corresponding components. Unless otherwise stated, the above words have no special meaning and therefore cannot be understood to limit the scope of protection of this application.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims (8)

1. A bionic micro-needle is characterized in that: it comprises a micro-needle needle body, the outer surface of the micro-needle needle body is provided with at least two grooves, and ridges are formed between adjacent grooves, and the grooves are formed along the edges of the grooves. The length direction of the microneedle body extends. 2 . The bionic microneedle according to claim 1 , wherein the microneedle body is in the shape of a vertebral body, the groove extends along the outer side of the vertebral body, and the width of the groove is from The top of the vertebral body gradually widens towards the bottom of the vertebral body. 3 . The bionic microneedle according to claim 2 , wherein the height of the vertebral body is 100 μm to 2000 μm, and the diameter of the bottom of the vertebral body is 100 μm to 1000 μm. 4 . 4 . The bionic microneedle according to claim 1 , wherein the groove comprises a first end and a second end, the first end extends to the bottom of the vertebral body, and the first end has a bottom end. 5 . The width is 10 μm˜100 μm, the second end extends to the top of the vertebral body, the width of the second end is 1 μm˜10 μm, and the depth of the groove is 1 μm˜20 μm. 5 . The bionic microneedle according to claim 1 , wherein there are several microneedle bodies, the plurality of microneedle bodies are arranged on the base in a matrix, and the microneedle bodies are arranged in a matrix. 6 . One end is fixed on the base, and the other end is a needle point and faces away from the base. 6 . A method for manufacturing a bionic microneedle, wherein the bionic microneedle according to any one of claims 1 to 5 is manufactured by 3D printing technology. 7 . 7 . The method for manufacturing biomimetic microneedles according to claim 6 , wherein the 3D printing technology adopts printing raw materials and prints the bionic microneedles, and the printing raw materials include photosensitive resin, reactive diluent and light. 8 . initiator. 8. The manufacture method of biomimetic microneedles according to claim 7, wherein the photoinitiator comprises one or any of benzoin and derivatives thereof, acetophenone derivatives or triaryl thiobellate salts A mixture of two or more.

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