WO2019157489A1

WO2019157489A1 - Durable echogenic coatings for improving ultrasound visibility of medical devices

Info

Publication number: WO2019157489A1
Application number: PCT/US2019/017610
Authority: WO
Inventors: Xiaoxi Kevin CHEN; Khristine CARROLL
Original assignee: AdvanSource Biomaterials Corp
Current assignee: Ekimas Corp
Priority date: 2018-02-12
Filing date: 2019-02-12
Publication date: 2019-08-15
Anticipated expiration: 2020-08-12

Abstract

The present invention discloses methods for producing durable echogenic coatings for improving ultrasound visibility of medical devices. The coating comprises a polymer matrix dispersed with hollow microspheres.

Description

DURABLE ECHOGENIC COATINGS FOR IMPROVING ULTRASOUND

VISIBILITY OF MEDICAL DEVICES

by

Cross-Reference to Related Application

[0001] This application claims priority of U.S. Provisional Patent Application No.

62/629,144, filed February 12, 2018, the entire contents of which are incorporated by reference herein.

Field of the Invention

[0002] The present invention discloses methods for producing durable echogenic coatings for improving ultrasound visibility of medical devices.

Background of the Invention

[0003] Ultrasound has been widely used to guide needle, catheter and guidewire placement and for vascular access, nerve blockade, drainage of pleural or ascitic fluid collections and percutaneous tracheostomy. Ultrasound allows identification of the target and collateral structures and real-time guidance to precisely place needles and other inserted devices.

[0004] The visibility of a needle or other inserted devices in ultrasound guided procedures is extremely important. Without accurate identification of the position of the needle it is possible that damage to collateral structures may occur. However, most medical devices have an acoustic impedance similar to that of the tissue into which the device is inserted. Consequently, visibility of the device can be poor and accurate placement can become extremely difficult. [0005] Gases have much lower acoustic impedance than liquids and solids due to their high compressibility. Accordingly, gas bubbles have a high degree of ultrasonic visibility compared to organ tissues because of their large impedance difference. Some prior arts have used in situ bubble formation methods. For example, in US 7,235,052, the echogenic coating is composed of multiple layers of coatings, in which two bubble generating elements (such as an acid and a carbonated base) are dispersed separately in two different layers of coatings; when the coatings are in contact with a fluid, these two bubble generating elements mix by diffusion and react with each other to form bubbles. Another example is US 2011/0104068 Al, in which the two bubble generating elements are mixed together in one single layer of coating; they do not react with each other in anhydrous environment and they will react and generate bubbles when the coatings are in contact with an aqueous solution.

[0006] The in situ bubble formation methods have some disadvantages: the echogenic effect is relatively short lived due to the escape of bubbles from the coatings to the environment; and the echogenic coatings are not durable due to the physical changes of the coatings caused by bubble formations, which can weaken the adherence of the coatings on the substrate surface.

Summary of the Invention

[0007] In light of the foregoing, the present invention provides echogenic coatings that are stable and robust, that do not undergo physical changes during the usage of the coated needles and other devices. More specifically, the coating composition of the present invention comprises a matrix formed by polymer and/or other materials dispersed with hollow microspheres. The polymers used in the coating composition preferably adhere strongly to the substrate surfaces and allow a homogeneous dispersion of the hollow microspheres.

Brief Description of the Figures

[0008] FIG. 1 is a drawing representing a substrate coated using subject invention durable echogenic coating comprising a polymer matrix and a dispersion of hollow microspheres. [0009] FIG. 2 shows the comparison of 2 ultrasonograms. The one on the left corresponds to the ultrasonogram of an uncoated stainless-steel needle immersed in water. The one on the right corresponds to the ultrasonogram of a coated stainless-steel needle immersed in water. The coated stainless-steel needle was prepared using the durable echogenic coating of the subject invention, as described in Example D.

[0010] FIG. 3 shows the comparison of 2 ultrasonograms. The one on the left corresponds to the ultrasonogram of an uncoated stainless-steel needle inserted in a piece of pork. The one on the right corresponds to the ultrasonogram of a coated stainless-steel needle inserted in the same position of the same piece of pork. The coated stainless-steel needle was prepared using the durable echogenic coating of the subject invention, as described in Example D.

Detailed Description of the Invention

[0011] With reference to FIG. 1, the substrate, which is the outer surface of a needle or other medical apparatus and/or devices, is coated with a matrix formed by polymer and/or other materials dispersed with hollow microspheres.

[0016] The polymers used to form the polymer matrix preferably are biocompatible and have good tensile strength and adhesion to a wide array of metallic and polymeric substrates. Suitable polymers include those that have been used as polymeric coatings for medical devices such as polyurethane (PU), polymethylmethacrylate (PMMA), poly vinylalcohol (PVA), poly-N-vinylpyrrolidone (PVP), polyethylene oxide (PEO), and copolymers thereof. Mixtures and blends of these polymers also can be used. Other matrix based coatings or jackets can also be used.

[0017] Hollow microspheres used to be dispersed in the polymer matrix preferably are biocompatible and have good tensile strength. Suitable hollow microspheres include hollow glass microsphere with diameter from 1 to 100 micrometers.

[0018] The hollow microspheres and the polymers can be mixed together in one or more organic solvents to provide a coating composition. Suitable solvents that can be used include, but not limited to, tetrahydrofuran, acetone, methylethylketone, dimethylformamide, dimethyacetamide, ethylene carbonate, propylene carbonate, diglyme, N-methylpyrrolidone, ethyl acetate, ethylene and propylene glycol diacetates, alkyl ethers of ethylene and propylene glycol monoacetates, toluene, xylene and sterically hindered alcohols such as t-butanol and diacetone alcohol. In preferred embodiments, the organic solvent or solvent mixture is evaporative. For example, tetrahydrofuran can be used. The total solid loading can be between about 5 wt.% and about 30 wt.%, where the loading of the hollow microspheres is between about 1 wt.% and about 50 wt.% of that of the polymer.

[0019] To improve the echogenicity of a medical device, at least a portion of the surface of the medical device can be coated with the present coating composition. Various coating techniques such as spin coating, drop-casting, zone casting, dip coating, blade coating, and spraying can be used, depending on the shape of the medical device. For example, the medical device can be an elongated member such as a catheter, a guidewire, or a needle, or a planar or spherical member such as an implant or a balloon. The thickness of the coating should be sufficient to entrap hollow microspheres having a diameter between about 1 pm and about 100 pm. Accordingly, typical thickness of the coating can range from about 0.01 mm to about 0.2 mm. The thickness achieved by one application of the coating composition will depend on the viscosity of the coating composition, the coating method, as well as the speed and the temperature at which the coating is applied. In some embodiments, multiple applications of the coating may be needed to build up the required thickness. The coating is then allowed to dry.

EXAMPLES

Example A

[0020] Stainless-steel needles were coated with the subject invention method. A coating solution was prepared by first dissolving 5% (w/v) ChronoFlex AL in tetrahydrofuron, followed by mixing 2% (w/v) hollow glass microspheres (11 pm diameter) in the ChronoFlex solution until a homogeneous solution is obtained. Stainless-steel needles were then dipped into the coating solution and lifted up slowly. The stainless-steel needles were then dried at room temperature for 30 minutes. Example B

[0021] Stainless-steel needles were coated with the subject invention method. A coating solution was prepared by first dissolving 5% (w/v) ChronoFlex AL in tetrahydrofuron, followed by mixing 2% (w/v) hollow glass microspheres (18 pm diameter) in the ChronoFlex solution until a homogeneous solution is obtained. Stainless-steel needles were then dipped into the coating solution and lifted up slowly. The stainless-steel needles were then dried at room temperature for 30 minutes.

Example C

[0022] Stainless-steel needles were coated with the subject invention method. A coating solution was prepared by first dissolving 5% (w/v) ChronoFlex AL in tetrahydrofuron, followed by mixing 2% (w/v) hollow glass microspheres (30 pm diameter) in the ChronoFlex solution until a homogeneous solution is obtained. Stainless-steel needles were then dipped into the coating solution and lifted up slowly. The stainless-steel needles were then dried at room temperature for 30 minutes.

Example D

[0023] Stainless-steel needles were coated with the subject invention method. A coating solution was prepared by first dissolving 5% (w/v) ChronoFlex AL in tetrahydrofuron, followed by mixing 2% (w/v) hollow glass microspheres (50 pm diameter) in the ChronoFlex solution until a homogeneous solution is obtained. Stainless-steel needles were then dipped into the coating solution and lifted up slowly. The stainless-steel needles were then dried at room temperature for 30 minutes.

Example E

[0024] Stainless-steel needles prepared using the durable echogenic coating of the subject invention as described in Example D were compared with uncoated stainless-steel needles for ultrasound visibility in water. FIG. 2 shows the comparison of 2 ultrasonograms. The one on the left corresponds to the ultrasonogram of an uncoated stainless-steel needle immersed in water. The one on the right corresponds to the ultrasonogram of a coated stainless-steel needle immersed in water. The coated needle has significantly improved ultrasound visibility compared to the uncoated needle.

Example F

[0025] Stainless-steel needles prepared using the durable echogenic coating of the subject invention as described in Example A were compared with uncoated stainless-steel needles for ultrasound visibility when they were inserted in a piece of pork. FIG. 2 shows the comparison of 2 ultrasonograms. The one on the left corresponds to the ultrasonogram of an uncoated stainless-steel needle inserted in a piece of pork. The one on the right corresponds to the ultrasonogram of a coated stainless-steel needle inserted in the same position of the same piece of pork. The coated needle has significantly improved ultrasound visibility compared to the uncoated needle.

Example G

[0026] Stainless-steel needles prepared using the durable echogenic coating of the subject invention as described in Example A were tested for durability. The coated needles were soaked in water, 0.1 M hydrochloric acid solution (pH ~ 1), and 0.1 M sodium carbonate solution (pH ~ 8.5) for 1 hour respectively. The coatings remain intact after soaking.

[0027] The present teachings can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the present teachings described herein. The scope of the present teachings is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

What is Claimed is:

1. A medical device comprising a coating for improving ultrasound visibility, wherein the coating comprises hollow microspheres dispersed within a polymer matrix.

2. A medical device of Claim 1, wherein the polymer matrix includes polyurethanes.

3. A medical device of Claim 1, wherein the polymer matrix includes polycarbonate- based urethanes.

4. A medical device of Claim 1, wherein the polymer includes silicones.

5. A medical device of Claim 1, wherein the hollow microspheres include glass microspheres.

6. A medical device of Claim 1, wherein the hollow microspheres have a diameter between 1 to 100 micrometers.

7. A medical device of Claim 1, wherein the weight-to-weight ratio of hollow microspheres to matrix is between 0.1 to 10.

8. A medical device of Claim 1, wherein the coating is prepared by dipping the substrate in the coating solution containing the matrix and the hollow microspheres.

9. A medical device of Claim 8, wherein the coating solution contains 0.1 - 20% (weight to volume) of the combined matrix and hollow microspheres.

10. A medical device of Claim 8, wherein the solvent is either tetrahydrofuran, dimethylacetamide, or a mixture of both. 11 A medical device of Claim 8, wherein a multiple dipping process is used to obtain the coating.