Balloon catheter for drug delivery

Abstract

The present invention provides a balloon catheter for drug delivery, comprising: a shaft; a balloon mounted on the shaft and arranged so as to be inflated toward the inner wall of a blood vessel; and a drug delivery coating layer coated on the balloon and configured to deliver a drug to a lesion of the blood vessel when the balloon is inflated, wherein the drug delivery coating layer has a semicrystalline surface structure.

Description

Balloon catheter for drug delivery

[0001] The present invention relates to a balloon catheter used to dilate a lesion site of a blood vessel and also to deliver a drug to the lesion site.

[0002]

[0003] In general, a catheter is a general term for a thin tube inserted into the body. In medical settings, catheters are used for a variety of purposes, including intravascular injections, coronary artery dilation, urethral insertion, tracheal insertion, and laparoscopic surgery.

[0004] For example, a balloon catheter for coronary artery dilation has an inflation balloon attached to the tip of the shaft inserted into the blood vessel. The balloon may be coated with a drug. As the balloon expands and contacts the blood vessel wall, the blood vessel dilates and the drug is delivered into the blood vessel. The delivered drug then acts on the blood vessel and its surrounding tissues.

[0005] As the balloon catheter advances through the blood vessel to the lesion, the drug is lost to the blood flow and other factors. If the drug coating layer is uneven and easily peels off, the degree of loss is significantly increased. Ultimately, even if the drug remains in the balloon and acts on the lesion, sustained drug delivery is difficult if the duration of its residence in the blood vessel is short.

[0006] The background technology described above is technical information that the inventor possessed for the purpose of deriving embodiments of the present invention or acquired during the derivation process, and cannot necessarily be said to be publicly known technology disclosed to the general public prior to the present application.

[0007]

[0008] One object of the present invention is to provide a balloon catheter for drug delivery, which reduces the loss of drug occurring during movement of the catheter within a blood vessel and ultimately increases the delivery rate of the drug remaining in the balloon to the blood vessel.

[0009]

[0010] According to one aspect of the present invention for achieving the above-described task, a drug delivery balloon catheter comprises: a shaft; a balloon mounted on the shaft and positioned to expand toward the inner wall of a blood vessel; and a drug delivery coating layer coated on the balloon and configured to deliver a drug to a lesion of the blood vessel when the balloon expands, wherein the drug delivery coating layer may have a semi-crystalline surface structure.

[0011] Here, the drug delivery coating layer may have a crystallinity of 40 to 60%.

[0012] Here, the drug delivery coating layer is formed by applying a composition solution in which the drug composition is dissolved in a solvent to the balloon, and the solvent may be a mixture of ethanol and water.

[0013] Here, the content of water in the solvent may be lower than that of ethanol.

[0014] Here, the solvent may contain 4 to 6 volume % of the water.

[0015] Here, a hydrophilic coating layer formed between the balloon and the drug delivery coating layer may be further included.

[0016] Here, the hydrophilic coating layer may include hyaluronic acid.

[0017] According to another aspect of the present invention, a drug delivery balloon catheter comprises: a shaft; a balloon mounted on the shaft; and a drug delivery coating layer having a semi-crystalline surface structure and formed to deliver a drug to a lesion of a blood vessel, wherein the drug delivery coating layer is formed by applying a composition solution in which a drug composition is dissolved in a solvent to the balloon, and the solvent may be a mixture of a first solvent and a second solvent having different vaporization rates.

[0018] Here, the drug delivery coating layer may have a crystallinity of 40 to 60%.

[0019] Here, the first solvent may have a first vaporization rate that causes the surface of the material produced as the composition solution dries to become amorphous, and the second solvent may have a second vaporization rate that causes the surface of the material produced as the composition solution dries to become crystalline.

[0020] Here, the first solvent is ethanol and the second solvent is water, and the solvent may contain water at a lower content than the ethanol.

[0021] Here, a hydrophilic coating layer formed between the balloon and the drug delivery coating layer may be further included.

[0022]

[0023] According to the drug delivery balloon catheter of the present invention configured as described above, since the drug delivery coating layer coated on the balloon mounted on the shaft has a semi-crystalline surface structure, the loss of drug occurring during movement of the catheter within the blood vessel is reduced, and the final delivery rate of the remaining drug to the blood vessel can be increased.

[0024] This could reduce the likelihood of repeating vasodilator and drug delivery procedures for patients. This could lower the risk of sudden death and reduce the physical and financial burden on patients.

[0025]

[0026] FIG. 1 is a perspective view showing a balloon catheter (100) for drug delivery according to one embodiment of the present invention.

[0027] Fig. 2 is a cross-sectional view showing the drug delivery balloon catheter (100) of Fig. 1 advanced within a blood vessel.

[0028] Fig. 3 is a cross-sectional view showing a state in which the drug delivery balloon catheter (100) of Fig. 1 delivers a drug to a blood vessel.

[0029] Figure 4 is an image diagram showing the experimental results showing the surface structure of a drug delivery coating layer according to the composition of the solvent.

[0030] Figure 5 is a graph showing the experimental results showing the drug loss rate and delivery rate of the drug delivery coating layer according to the composition of the solvent.

[0031]

[0032] Hereinafter, a preferred embodiment of the present invention will be described in detail with reference to the attached drawings.

[0033] The present invention is not limited to the embodiments disclosed below, but can be implemented in various forms and with various modifications. However, these embodiments are provided to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention. Therefore, the present invention is not limited to the embodiments disclosed below, but should be understood to include all modifications, equivalents, and substitutes included within the technical spirit and scope of the present invention, as well as substitutions or additions of the components of one embodiment with those of another embodiment.

[0034] The attached drawings are merely intended to facilitate understanding of the embodiments disclosed in this specification, and should not be construed as limiting the technical ideas disclosed in this specification, but should be understood to encompass all modifications, equivalents, and substitutes included within the spirit and technical scope of the present invention. In the drawings, the components may be expressed in exaggerated sizes or thicknesses for ease of understanding, but the scope of protection of the present invention should not be construed as being limited thereby.

[0035] The terminology used in this specification is only used to describe specific implementations or examples and is not intended to limit the present invention. In addition, the singular expression includes the plural expression unless the context clearly indicates otherwise. In the specification, terms such as "comprises" and "consists of" are intended to indicate the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification. In other words, it should be understood that terms such as "comprises" and "consists of" do not exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0036] Terms that include ordinal numbers, such as first, second, etc., may be used to describe various components, but the components are not limited by these terms. These terms are used solely to distinguish one component from another.

[0037] When a component is referred to as being "connected / connected" or "connected" to another component, it should be understood that it may be directly connected / connected to that other component, or that there may be other components in between. Conversely, when a component is referred to as being "directly connected / connected" or "directly connected" to another component, it should be understood that there are no other components in between.

[0038] When a component is referred to as being "above" or "below" another component, it should be understood that it is not only positioned directly above that other component, but that there may also be other components present in between.

[0039] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0040] FIG. 1 is a perspective view showing a balloon catheter (100) for drug delivery according to one embodiment of the present invention.

[0041] Referring to this drawing, a balloon catheter (100) for drug delivery may be composed of a hub (110), a shaft (120), a soft tip (130), a balloon (140), and a drug delivery coating layer (150).

[0042] The hub (110) has a shape suitable for the operator to hold in his hand and apply force. The hub (110) may also be provided with a hollow passage.

[0043] The shaft (120) is a long member connected to the hub (110). The distal end of the shaft (120) can be connected to a soft tip (130) to be described later. The shaft (120) functions to transmit the force to the soft tip (130) when the operator holds the hub (110) and inserts the balloon (140) into a blood vessel.

[0044] The soft tip (130) is a member attached to the distal end of the shaft (120). The soft tip (130) often collides with the inner wall of the blood vessel as it enters the blood vessel from the tip of the catheter (100). To prevent damage to the blood vessel due to the collision, the soft tip (130) may be formed of a material with superior ductility than the shaft (120). Depending on a method such as combining the materials of the shaft (120), the soft tip (130) (and hub (110)) may not be provided separately but may be formed integrally with the shaft (120).

[0045] The balloon (140) is installed to surround the distal end of the shaft (120). The balloon (140) can be inflated by the pressure of a fluid, such as a contrast agent, supplied through the hub (110) and the shaft (120). The balloon (140) dilates a blood vessel at a location desired by the practitioner, thereby improving vascular occlusion. The practitioner can also identify the location of the balloon (140) through the contrast agent injected into the balloon (140).

[0046] The drug delivery coating layer (150) is formed by applying a composition solution to the surface of the balloon (140). The composition solution is formed by dissolving the drug composition in a solvent. The drug composition includes a drug for absorption into a lesion site of a blood vessel, and the drug is delivered toward the lesion site from the drug delivery coating layer (150). In order to reduce the loss rate, which is the rate at which the drug is lost during movement, and increase the delivery rate, which is the rate at which the drug is delivered to the blood vessel, the drug delivery coating layer (150) may have a semi-crystalline surface structure.

[0047] The semi-crystalline surface structure is a hybrid of a crystalline surface structure and an amorphous surface structure. The amorphous surface structure reduces the degree of peeling of the drug delivery coating layer (150) while the balloon catheter (100) advances within a blood vessel. As a result, the amorphous surface structure reduces the loss rate. The crystalline surface structure ensures that the drug is continuously delivered to the inner wall of the blood vessel. As a result, the crystalline surface structure increases the delivery rate. Consequently, the semi-crystalline surface structure increases the final delivery amount of the drug to the blood vessel.

[0048] Fig. 2 is a cross-sectional view showing the drug delivery balloon catheter (100) of Fig. 1 advanced within a blood vessel.

[0049] Referring to this drawing, the blood vessels shown are the aorta (A) and the coronary artery (C), a microvessel connected to it. The guiding catheter (GC) can be inserted with sufficient space into the aorta (A), but not into the coronary artery (C). The guiding catheter (GC) can only be inserted as far as the beginning of the coronary artery (C).

[0050] While the balloon catheter (110) moves within the guiding catheter (GC), the drug is protected by the guiding catheter (GC). After the drug delivery coating layer (150) exits the guiding catheter (GC), the drug is no longer protected by the guiding catheter (GC). Specifically, the drug delivery coating layer (150) is directly exposed to blood flow, etc., in the section (DL) from the beginning of the coronary artery (C) to the lesion (L). Such an environment can cause significant loss of the drug.

[0051] However, a significant portion of the drug is prevented from leaving the balloon (140) due to the surface structure of the drug delivery coating layer (150). This is because, among the semi-crystalline surface structures, the portion having the amorphous surface structure prevents the drug delivery coating layer (150) from being peeled off. As a result, the drug delivery coating layer (150) can be positioned corresponding to the lesion (L) while retaining the maximum amount of drug.

[0052] Fig. 3 is a cross-sectional view showing a state in which the drug delivery balloon catheter (100) of Fig. 1 delivers a drug to a blood vessel.

[0053] Referring to this drawing, the drug composition of the drug delivery coating layer (150) may include a drug, an adhesive fixative, and a dissolution inhibitor.

[0054] The drug may include at least one selected from the group consisting of cytostatics, restenosis inhibitors, reepithelialization promoters, and anti-inflammatory agents. Accordingly, the drug may be selected from the group consisting of everolimus, sirolimus, paclitaxel, heparin, amoxicillin, spaclitaxel, doxorubicin, ganciclovir, verapramil, clonidine, simvastatin, and combinations thereof. For example, everolimus is a cytostatic agent that inhibits cell division and angiogenesis, and is a type of mTOR inhibitor.

[0055] The above-mentioned anti-dissolution agent is an element that prevents the dissolution of the drug, for example, everolimus, in the blood. Specifically, while the balloon (140) is contracted on the shaft (120, see FIG. 1) and moves along the blood vessel (C), the anti-dissolution agent can prevent the everolimus from being dissolved by the blood or the like within the blood vessel (C). The anti-dissolution agent may include a natural resin such as shellac.

[0056] The above adhesive fixative is a component that adheres and fixes the drug to the balloon (140). Mussel adhesive protein (MAP), a natural substance, can be used as the adhesive fixative. The mussel adhesive protein is an adhesive made of proteins produced by mussels to survive by adhering to underwater surfaces such as rocks. Therefore, the mussel adhesive protein exhibits adhesive properties even in blood, enhancing drug delivery performance to blood vessels and preventing drug loss in the bloodstream.

[0057] A hydrophilic coating layer (160) may be additionally provided between the drug delivery coating layer (150) and the balloon (140). The hydrophilic coating layer (160) may be applied to the surface of the balloon (140) to strengthen the bonding force between the balloon (140) and the drug delivery coating layer (150). The hydrophilic coating layer (160) may include hyaluronic acid (HA). The hyaluronic acid is a linear polysaccharide that has an anionic charge and is composed of a glycoaminoglycan structure. The hyaluronic acid is found throughout the body, from the eye vitreous to the extracellular matrix (ECM) of cartilage tissue. The hyaluronic acid has excellent viscoelasticity, high moisturizing capacity, high biocompatibility, and hygroscopicity.

[0058] Figure 4 is an image diagram showing the experimental results showing the surface structure of a drug delivery coating layer according to the composition of the solvent.

[0059] Referring to this drawing, different solvents may be used in the composition solution for forming the drug delivery coating layer (150, see FIG. 1). Specifically, a first solvent and a second solvent having different vaporization rates may be mixed to form the solvent. When the composition solution is made using only the first solvent, the vaporization rate of the first solvent (the first vaporization rate) may cause the surface of the material produced as the composition solution dries to have amorphous properties. In contrast, when the composition solution is made using only the second solvent, the vaporization rate of the second solvent (the second vaporization rate) may cause the surface of the material produced as the composition solution dries to have complete crystallinity. The first vaporization rate may be greater than the second vaporization rate.

[0060] In this embodiment, ethanol is used as the first solvent, and water is used as the second solvent. If the water content in the solvent is higher than that in the ethanol, the drug delivery coating layer (150) can approach complete crystallinity. Therefore, the water content in the solvent may be lower than that in the ethanol.

[0061] The water content can be determined by considering the experimental results. According to the experimental results, when the water is contained in the solvent at 0 volume %, the surface of the drug delivery coating layer (150) becomes amorphous. When the water is contained at 10 volume % or more, the surface approaches a completely crystalline structure. When the water is contained at 1 to 3 volume %, the crystallinity of the drug delivery coating layer (150) becomes 20 to 40%. When the water is contained at 4 to 6 volume %, the crystallinity becomes 40 to 60%. It can be confirmed that the crystallinity increases as the water content increases.

[0062] Figure 5 is a graph showing the experimental results showing the drug loss rate and delivery rate of the drug delivery coating layer according to the composition of the solvent.

[0063] Referring to this drawing (and FIG. 4), the loss rate and the transfer rate according to the content of water in the solvent are relative values ​​when the water content is 10% by volume or more and is set to 100%.

[0064] It can be seen that as the water content in the solvent increases, the loss rate gradually increases. The degree of change in the loss rate as the water content increases is similar.

[0065] The above-mentioned transmission rate also increases as the water content increases. However, the pattern of increase is not gradual like that of the loss rate. Specifically, when the water content is 4 to 6 volume%, the transmission rate increases in a stepwise manner compared to other sections. While the transmission rate is approximately 88% when the water content is 1 to 3 volume%, the transmission rate reaches 98% when the water content is 4 to 6 volume%. When the water content is 7 to 9 volume%, the transmission rate is approximately 99%, and the degree of change is gradual.

[0066] Considering the above experimental results, when the water content is 7% by volume or more (7 to 9% by volume and 10% by volume or more), the transfer rate and the loss rate are high. Although the high transfer rate is positive, the high loss rate does not result in the highest final transfer amount. When the water content is 3% by volume or less (0% by volume and 1 to 3% by volume), the low loss rate is positive, but the transfer rate is also low. Accordingly, the final transfer amount is also not the highest. On the other hand, when the water content is 4 to 6% by volume, the loss rate is somewhat higher than when the water content is 3% by volume or less, but the transfer rate increases dramatically, achieving the highest final transfer amount. Accordingly, it is preferable that the water content be 4 to 6% by volume in the solution. In that case, the crystallinity becomes 40 to 60% (see Fig. 4).

[0067]

[0068] The present invention has industrial applicability in the field of manufacturing balloon catheters for drug delivery.

Claims

1. Shaft; a balloon mounted on the shaft and positioned to inflate toward the inner wall of the blood vessel; and A drug delivery coating layer coated on the above balloon and configured to deliver a drug to a lesion of a blood vessel when the balloon is inflated, The above drug delivery coating layer is, A balloon catheter for drug delivery having a semi-crystalline surface structure.

2. In paragraph 1, The above drug delivery coating layer is, A balloon catheter for drug delivery having a crystallinity of 40 to 60%.

3. In paragraph 1, The above drug delivery coating layer is, A drug composition is formed by applying a solution of the composition dissolved in a solvent to the balloon, The above solvent is, A balloon catheter for drug delivery, which is a mixture of ethanol and water.

4. In paragraph 3, The content of water in the above solvent is, A balloon catheter for drug delivery, lower than the above ethanol.

5. In paragraph 3, The above solvent is, A balloon catheter for drug delivery containing 4 to 6 volume % of the above water.

6. In paragraph 1, A drug delivery balloon catheter further comprising a hydrophilic coating layer formed between the balloon and the drug delivery coating layer.

7. In paragraph 6, The above hydrophilic coating layer, A balloon catheter for drug delivery comprising hyaluronic acid.

8. Shaft; a balloon mounted on the above shaft; and It comprises a drug delivery coating layer having a semi-crystalline surface structure and formed to deliver a drug to a lesion of a blood vessel, The above drug delivery coating layer is, A drug composition is formed by applying a solution of the composition dissolved in a solvent to the balloon, The above solvent is, A balloon catheter for drug delivery, comprising a mixture of a first solvent and a second solvent having different vaporization rates.

9. In paragraph 8, The above drug delivery coating layer is, A balloon catheter for drug delivery having a crystallinity of 40 to 60%.

10. In paragraph 8, The above first solvent is, The composition solution has a first vaporization rate that makes the surface of the material produced as it dries amorphous, The second solvent is, A drug delivery balloon catheter having a second vaporization rate that causes the surface of the material produced as the above composition solution dries to become crystalline.

11. In paragraph 10, The first solvent is ethanol and the second solvent is water, The above solvent is, A balloon catheter for drug delivery, wherein the water content is lower than the ethanol content.

12. In paragraph 8, A drug delivery balloon catheter further comprising a hydrophilic coating layer formed between the balloon and the drug delivery coating layer.

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