WO2025170415A1 - Microneedle drug delivery stent - Google Patents

Abstract

Disclosed is a microneedle drug delivery stent capable of locally delivering a drug into a luminal organ. The microneedle drug delivery stent comprises: a coating stent; and a microneedle formed in the coating stent to carry a drug, wherein the coating stent may have a coating groove in which the microneedle is formed.

Description

Microneedle drug delivery stent

The present invention relates to a microneedle drug delivery stent.

Lesions in various non-vascular organs, such as the biliary tract, esophagus, gastrointestinal tract, trachea, and ureters, can cause narrowing of the ducts of these organs. For organs with such problems, various types of stents are used to widen the ducts.

Stent therapy is a promising treatment option for gastrointestinal cancer-related obstructions, demonstrating efficacy in both malignant and benign gastrointestinal strictures. However, stent restenosis due to granulation tissue overgrowth within the stent, as well as symptom recurrence due to stent migration during digestive peristalsis, remain challenges that must be addressed. Consequently, the need for the development of functional stents for various gastrointestinal strictures is rapidly increasing.

In the case of gastrointestinal stenotic diseases, exposure to various digestive and bodily fluids, unlike the vascular environment, poses challenges in effective drug delivery and a high risk of drug loss. Furthermore, clinical trials of gastrointestinal drug-eluting stents have limitations, failing to demonstrate significant differences. To prevent gastrointestinal stent restenosis and ensure stable stent insertion, local delivery of various drugs to non-vascular intimal lesions early after stent insertion is necessary. These drugs promote non-intimal hyperplasia and suppress tissue overgrowth.

Accordingly, there is a need for a technology that can effectively treat gastrointestinal strictures by applying microneedle technology to deliver an approved anti-proliferative agent into a film-type membrane attached to or covered by a non-vascular stent and delivering it into an organ with malignant stricture (esophagus, duodenum, biliary tract, pancreas, colon, small intestine, etc.) with enhanced fixation and designing a film-type membrane to locally deliver the drug to non-vascular inner wall lesions.

(Prior art literature)

(Patent Document)

(Patent Document 1) U.S. Registration Publication No. US 8740973 (registered on June 3, 2014)

Embodiments of the present invention aim to provide a microneedle drug delivery stent capable of locally delivering a drug to a non-vascular endovascular lesion.

A microneedle drug delivery stent according to an embodiment of the present invention comprises a membrane stent; and microneedles formed in the membrane stent to contain a drug, wherein the membrane stent is provided with membrane grooves in which the microneedles are formed.

In addition, the above-described membrane stent includes a plurality of stent wire portions connected in a mesh form; and a stent membrane portion including a material capable of elastic restoration, wherein the stent wire portions can be arranged such that the membrane grooves are provided in the spaces between the plurality of stent wire portions.

Additionally, the diameter of the stent wire portion may be greater than or equal to the height of the microneedle.

Additionally, the microneedles may be positioned closer to the stent wire portion than to the center of the membrane groove.

In addition, the arrangement shape of the microneedles is similar to the arrangement shape of the plurality of stent wire parts, and the microneedles can be arranged spaced apart from each other on the membrane groove.

In addition, the stent wire portion may be arranged in a diamond cell shape on the stent film portion, and a plurality of the microneedles may be arranged spaced apart on the film groove in a diamond cell shape with a size smaller than the shape of the stent film portion.

Additionally, the above-mentioned membrane stent may include a biodegradable component that melts and biodegrades at the lesion site after a predetermined period of time.

Additionally, the membrane stent can be biodegraded in the patient's body for a longer period of time than the drug release time for the drug to be released from the microneedles.

Embodiments of the present invention have the advantage that microneedles loaded with anti-proliferative drugs are formed in a membrane stent.

In addition, embodiments of the present invention have the advantage of enabling effective tissue hyperproliferation inhibition treatment through an antiproliferative agent loaded in the microneedles that is released after a certain period of time when a microneedle drug delivery stent is inserted into a luminal organ with malignant stenotic disease.

Additionally, embodiments of the present invention have the advantage of reducing frictional interference between microneedles.

Additionally, embodiments of the present invention have the advantage that microneedles can be maintained and preserved on a membrane stent without damage.

Additionally, embodiments of the present invention have the advantage of compressing the membrane stent and loading it into a narrow diameter delivery system.

Additionally, embodiments of the present invention have the advantage of minimizing the diameter of the delivery system.

FIG. 1 is a perspective view illustrating a microneedle drug delivery stent according to one embodiment of the present invention.

Figure 2 is a cross-sectional view taken along the “Ⅰ-Ⅰ” section of Figure 1.

FIG. 3 is a side view illustrating a microneedle drug delivery stent according to one embodiment of the present invention.

Figures 4 and 5 are diagrams showing a compressed state of a microneedle drug delivery stent according to one embodiment of the present invention.

FIGS. 6 and 7 are diagrams illustrating a state in which a microneedle drug delivery stent according to one embodiment of the present invention is compressed and inserted into a non-vascular inner wall of a luminal organ.

FIG. 8 is a diagram illustrating a state in which a microneedle drug delivery stent according to one embodiment of the present invention is restored to its original state and adhered to the inner wall of a non-vascular organ in the lumen.

Hereinafter, the configuration and operation of embodiments of the present invention will be described in detail with reference to the attached drawings. The following description is one of several aspects of the present invention eligible for patent claims, and may constitute a part of the detailed description of the present invention. However, in describing the present invention, specific descriptions of known configurations or functions may be omitted for clarity.

The present invention is susceptible to various modifications and encompasses numerous embodiments. Specific embodiments are illustrated in the drawings and described in detail in the description. However, this is not intended to limit the present invention to specific embodiments, but rather to encompass all modifications, equivalents, and alternatives falling within the spirit and technical scope of the present invention.

While terms including ordinal numbers, such as first, second, etc., may be used to describe various components, the components are not limited by such terms. These terms are used solely to distinguish one component from another. When a component is referred to as being "connected" or "connected" to another component, it should be understood that it may be directly connected or connected to that other component, but there may also be other components in between. The terminology used in this application is used only to describe specific embodiments and is not intended to limit the present invention. The singular expression "a," "an," and "the" include plural expressions unless the context clearly indicates otherwise.

As illustrated in FIGS. 1 to 4 , a microneedle drug delivery stent (10) according to one embodiment of the present invention may contribute to the treatment of lesions when inserted into a lumen of a blood vessel and releases drugs into non-vascular endovascular lesions. This microneedle drug delivery stent (10) may include a membrane stent (100) and microneedles (200).

The film stent (100) can maintain the overall shape of the microneedle drug delivery stent (10). The film stent (100) can be inserted into a lumen having a malignant stenotic disease. When the film stent (100) is inserted into the lumen, the film stent (100) can be inserted in a compressed state for easy insertion into the lumen. When the film stent (100) is positioned on a non-vascular endovascular lesion in the lumen, it can be restored to its original shape and adhere closely to the non-vascular endovascular lesion in the lumen.

The film stent (100) may include a biodegradable component that melts and biodegrades at the lesion site after a predetermined period of time. The film stent (100) may be biodegraded in the patient's body for a longer period of time than the drug release time for the drug to be released from the microneedle (200). For example, the biodegradable component may include Mg alloy, Polycaprolactone; PCL, Polylactide Acid; PLA, Poly-l-Lactic Acid; PLLA, Poly Lactic-co-Glycolic Acid; PLGA, etc. In the present embodiment, the film stent (100) is described as including a biodegradable component, but the film stent (100) may also include a non-degradable component in addition to the biodegradable component. For example, the non-degradable component may include Nitinol, Co-Cr alloy, etc. A membrane stent (100) may include a stent wire portion (110) and a stent membrane portion (120).

The stent wire portion (110) can support the overall shape of the microneedle drug delivery stent (10). The stent wire portion (110) can be arranged on the outer surface of the stent film portion (120). The stent wire portion (110) can include a material capable of elastic restoration. When the stent wire portion (110) is inserted into a luminal organ, it can be compressed in a pressurized state, and when it is positioned on a non-vascular inner wall lesion in the luminal organ and the pressurization is released, the stent wire portion (110) can be restored to its original shape. To maintain the pressurized state of the stent wire portion (110), a separate catheter device can be used.

The stent wire portion (110) may be provided in the form of a plurality of wire stents connected in a mesh form. A membrane groove (101) may be formed in a space between the plurality of stent wire portions (110). The membrane groove (101) may be a groove positioned at a lower height than the stent wire portion (110) on the stent membrane portion (120). A plurality of microneedles (200) may be formed in the membrane groove (101). For example, a plurality of microneedles (200) may be arranged in a form parallel to the stent wire portion (110) at the edge of the membrane groove (101).

The stent wire portion (110) may be formed on the stent film portion (120) with a diameter equal to or greater than the height of the microneedle (200). If the diameter of the stent wire portion (110) is equal to or greater than the height of the microneedle (200), the tip of the microneedle (200) may not normally protrude from the outer surface of the stent wire portion (110), and only when the microneedle drug delivery stent (10) is in close contact with a non-vascular inner wall lesion in a luminal organ may the tip of the microneedle (200) protrude from the outer surface of the stent wire portion (110) and come into contact with the non-vascular inner wall lesion. A cross-section in a direction perpendicular to the extension direction of the stent wire portion (110) may have a semicircular shape. The stent wire portion (110) may include a first wire portion (111) and a second wire portion (112).

The first wire portion (111) may be formed to extend in one direction on the outer surface of the stent film portion (120). For example, the first wire portion (111) may be formed to extend at a predetermined angle of inclination with respect to the axial direction of the stent film portion (120). When the first wire portion (111) intersects the second wire portion (112), the second wire portion (112) may form a film groove (101) in a grid shape (for example, a diamond cell shape).

The second wire portion (112) may be formed to extend in another direction on the outer surface of the stent film portion (120). For example, the second wire portion (112) may be formed to extend at a predetermined angle of inclination so as to intersect with the first wire portion (111) with respect to the axial direction of the stent film portion (120). When the second wire portion (112) intersects with the first wire portion (111), a grid-shaped film groove (101) may be formed in the space between the second wire portion (112) and the first wire portion (111).

The stent film portion (120) can support the stent wire portion (110). The stent film portion (120) can be provided in a cylindrical tube shape. A stent wire portion (110) and a film groove (101) can be formed on the outer surface of the stent film portion (120), that is, on the outer diameter surface of the stent film portion (120). In addition, microneedles (200) can be formed on the outer diameter surface of the stent film portion (120).

The stent membrane portion (120) can be compressed in a pressurized state when inserted into a lumen of an organ, and when positioned on a non-vascular inner wall lesion within the lumen of an organ and the pressurization is released, it can return to its original shape. The stent membrane portion (120) can include a material capable of elastic recovery. A separate catheter device can be used to maintain the pressurized state of the stent membrane.

The microneedle (200) can release a drug when the microneedle drug delivery stent (10) is inserted into a lumen of an organ. For example, when the microneedle drug delivery stent (10) is in close contact with a non-vascular inner wall lesion, the microneedle (200) releases the drug for a certain period of time after a certain period of time has elapsed, thereby enabling drug treatment of the non-vascular inner wall lesion.

The microneedle (200) can be loaded with various types of drugs that promote endothelial proliferation and inhibit tissue overgrowth. In the present embodiment, the drug may be an anti-proliferative drug that inhibits proliferation of non-vascular endothelial lesions. When the microneedle drug delivery stent (10) adheres to the non-vascular endothelial lesion, the microneedle (200) can perform tissue overgrowth inhibition treatment for the non-vascular endothelial lesion.

The microneedle (200) may be arranged in the membrane groove (101) of the membrane stent (100). The extent to which the microneedle (200) protrudes from the membrane groove (101) may be smaller than the extent to which at least one of the first wire portion (111) and the second wire portion (112) protrudes from the membrane groove (101). The microneedle (200) may be provided in multiple pieces. The multiple microneedles (200) may be arranged adjacent to at least one of the first wire portion (111) and the second wire portion (112) and may be arranged along the direction in which at least one of the first wire portion (111) and the second wire portion (112) extends. The multiple microneedles (200) may be arranged spaced apart from each other in the membrane groove (101) in a shape similar to the shape of the arrangement of the multiple stent wire portions (110). For example, a plurality of microneedles (200) may be spaced apart and arranged on the membrane groove (101) in a diamond cell shape smaller than the shape of the stent membrane portion (120). The plurality of microneedles (200) may be arranged closer to the stent wire portion (110) than the center of the membrane groove (101).

Hereinafter, the function of a microneedle drug delivery stent having such a configuration is described as follows.

As illustrated in FIGS. 5 to 8, the microneedle drug delivery stent (10) can be inserted into the lumen (C) by a separate catheter device. When the microneedle drug delivery stent (10) is inserted into the lumen (C), the microneedle drug delivery stent (10) can be compressed in the inner diameter direction. When the microneedle drug delivery stent (10) is compressed in the inner diameter direction, the microneedle drug delivery stent (10) can be easily inserted into the lumen (C).

As illustrated in FIG. 8, when the microneedle drug delivery stent (10) is positioned on a non-vascular inner wall lesion within a luminal organ, the microneedle drug delivery stent (10) can be restored to its original shape. When the microneedle drug delivery stent (10) is restored to its original shape, the microneedle drug delivery stent (10) can adhere to the non-vascular inner wall lesion within the luminal organ (C).

When the microneedle drug delivery stent (10) is adhered to a non-vascular inner wall lesion in a luminal organ (C), the microneedles (200) of the microneedle drug delivery stent (10) release the drug for a predetermined period of time after a certain period of time has elapsed, so that tissue hyperproliferation suppression treatment for the non-vascular inner wall lesion can be performed.

Meanwhile, the manufacturing method of the microneedle drug delivery stent (10) according to the present invention is described as follows.

First, a flexible microneedle mold with a masked stent pattern may be provided. The microneedle mold may be a mold for forming microneedles into the stent membrane. Once the microneedle mold is provided, a pre-solution containing a biodegradable polymer and the drug to be delivered may be prepared, and the prepared pre-solution may be applied to the microneedle mold.

Afterwards, the free solution can be filled into the microneedle mold by removing air bubbles under vacuum within the pressure chamber. Alternatively, the free solution can be filled by applying high pressure to the pressure chamber to force the free solution into the mold. After the residual free solution on the surface of the microneedle mold is removed using a doctor-blading technique, the film can be dried by making seamless contact with the surface of the microneedle mold.

After the free solution within the microneedle mold has sufficiently dried, the film is removed, allowing the microneedles formed within the mold to be transferred to the film, and empty spaces are formed along the stent pattern, making it easier to bond with the stent.

As described above, when a microneedle drug delivery stent (10) is inserted into a luminal organ with malignant stenotic disease, effective tissue hyperproliferation suppression treatment can be achieved through the drug released from the microneedles after a certain period of time. In addition, it has excellent advantages such as the microneedles can be maintained and preserved without damage on the film stent, and the diameter of the delivery system can be minimized according to the characteristics of the stent delivery method that compresses the film stent and loads it into a narrow-diameter delivery system.

The embodiments described above merely illustrate some examples of the technical idea of the present invention, and the scope of the technical idea of the present invention is not limited to the described embodiments. Various changes, modifications, or substitutions may be possible within the scope of the technical idea of the present invention by a person skilled in the art, and all such implementations should be considered to fall within the scope of the technical idea of the present invention.

Claims (8)

membrane stent; and A microneedle formed on the membrane stent to contain a drug, The above membrane stent A membrane groove in which the above microneedles are formed is provided. Microneedle drug delivery stent. In the first paragraph, The above membrane stent A plurality of stent wires connected in a mesh shape; and A stent membrane portion comprising a material capable of elastic restoration, The above stent wire portion is arranged so that the membrane groove is provided in the space between the plurality of the above stent wire portions. Microneedle drug delivery stent. In the second paragraph, The diameter of the above stent wire portion is greater than or equal to the height of the microneedle. Microneedle drug delivery stent. In the second paragraph, The above microneedles Positioned closer to the stent wire portion than the center of the above membrane groove, Microneedle drug delivery stent. In the second paragraph, The arrangement shape of the above microneedles is similar to the arrangement shape of the plurality of stent wire parts, The above microneedles are spaced apart on the film groove, Microneedle drug delivery stent. In paragraph 5, The above stent wire portion It is arranged in a diamond cell shape on the above stent film portion, A plurality of the above microneedles A diamond cell shape smaller than the shape of the stent membrane portion is spaced apart from the membrane groove. Microneedle drug delivery stent. In the first paragraph, The above membrane stent Contains a biodegradable component that dissolves and biodegrades when a certain amount of time has passed at the lesion site. Microneedle drug delivery stent. In paragraph 7, The above membrane stent Biodegradable in the patient's body for a longer period of time than the drug release time during which the drug is released from the microneedles. Microneedle drug delivery stent.