WO2000001439A1

WO2000001439A1 - Non-occlusive applicator for coaxially enclosing a vessel

Info

Publication number: WO2000001439A1
Application number: PCT/US1999/014771
Authority: WO
Inventors: Timothy R. Billiar; Masayuki Miyagishima
Original assignee: University Of Pittsburgh Of The Commonwealth System Of Higher Education
Priority date: 1998-07-01
Filing date: 1999-06-29
Publication date: 2000-01-13
Also published as: WO2000001439A8; AU4846799A

Abstract

The present invention provides a non-occlusive applicator. The applicator includes a shell and at least two end caps, all of which define a lumen. When placed around a vessel, the lumen is sealed from space immediately exterior to the applicator. The applicator is able to accommodate a fluid influent means and a fluid effluent means to expose the region of the vessel within the lumen to desired fluids or semifluids.

Description

NON-OCCLUSIVE APPLICATOR FOR COAXIALLY ENCLOSING A VESSEL

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT This invention was made, in part, with Government support under Grant

Number RO1-GM-44100 awarded by the National Institutes of Health. The United States Government may have certain rights in this invention.

TECHNICAL FIELD OF THE INVENTION The present invention relates to a non-occlusive applicator.

BACKGROUND OF THE INVENTION

In many medical procedures, it is desirable to supply medicaments to isolated regions of vessels, especially blood vessels. For example, drugs or genetic vectors can be supplied to isolated vascular regions to treat or prevent various vascular diseases (see, e.g., U.S. Patent 5,658,565). While many such medicaments can be supplied to vessels externally, such protocols are not without risk. For example, medicaments within fluids bathing such vessels diffuse into surrounding tissues, thus reducing the concentration (or titer) of medicament exposed to the vessel. Moreover, because of this diffusion, such protocols cannot be employed to deliver certain medicaments (notably viruses) for which ectopic delivery poses serious health risks.

To combat these concerns, medicaments are typically supplied to vessels internally, and a variety of endo vascular techniques, such as balloon angioplasty, intravascular stents, laser-assisted balloon angioplasty, double balloon catheterization, mechanical endarterectomy and vascular endoscopy, have been developed. For a review of endovascular alternatives, see generally Ahn, "Endovascular Surgery," in Vascular Surgery, A Comprehensive Review, W. S. Moore (ed.), W. B. Saunders & Co., Philadelphia (1993)). In application, an occlusive device, such as a balloon, is deployed at the proximal end of the desired region within the vessel to halt the flow of fluid, and a second occlusive device is also commonly deployed at the distal end of the desired region. Thereafter, fluid containing a desired medicament is introduced into the segregated region of the vessel to contact the vessel wall. Following the procedure, the occlusive devices are withdrawn so that fluid can again flow through the vessel.

While effective in delivering the medicament to the desired vessel region, these techniques present several drawbacks. Notably, some vessels (e.g., those supplying the brain and heart) cannot be occluded for periods of time needed to supply some medicaments (especially genetic vectors) to vascular tissue. Moreover, high velocity fluid flow through some vascular tissue immediately following such procedures renders it difficult to contain the medicament solely within the desired site, and residual ectopic delivery of some medicaments (e.g., viruses) represents a serious threat to the patient's health. In view of the foregoing problems, there exists a need for an applicator device for delivering solutions to vessels without causing occlusion.

BRIEF SUMMARY OF THE INVENTION

The present invention provides an applicator for delivering solutions to vessels without causing occlusion. The applicator includes a shell and at least two end caps, all of which define a lumen. When placed around a vessel, the lumen is sealed from space immediately exterior to the applicator. The applicator is able to accommodate a fluid influent means and a fluid effluent means to expose the region of the vessel within the lumen to desired fluids or semifluids, such as those containing medicaments. Because the applicator is sealed, the desired fluids or semifluids can be contained within the applicator and supplied only to the region of the vessel therein. This permits a high concentration of medicament to be maintained within the region of interest and minimizes contamination of surrounding tissue. Furthermore, because the applicator is non-occlusive, it can be employed to effectively deliver medicaments to vessels sensitive to even temporary occlusion. These and other advantages of the present invention, as well as additional inventive features, will be apparent from the accompanying drawings and in the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of the non-occlusive applicator in the unsealed position.

Figure 2 is a perspective view of the non-occlusive applicator in the sealed position and engaging a vessel.

Figure 3a is a cross-sectional view taken along the line 3-3 in Figure 2 of a portion of the shell of a non-occlusive applicator. Figure 3b is a magnified view of a portion of the shell of a non-occlusive applicator depicting one type of sealing means. Figure 4 is a schematic representation of an arrangement of an end portion of a non-occlusive applicator.

Figures 5a-5c depict components of an applicator through various steps of producing an applicator according to the present invention. Figure 5a depicts the applicator in the first step; Figure 5b depicts the applicator in the second step; and Figure 5c depicts the applicator in the third step. Figures 6a and 6b are perspective views of variant configurations of the non- occlusive applicator. Figure 6a depicts a curved applicator. Figure 6b depicts a bifurcated applicator.

DETAILED DESCRIPTION OF THE INVENTION

With reference to Figures 1 and 2, the applicator 1 is constructed for receiving and enclosing a vessel 14 coaxially. In this context, the term "vessel" represents any generally tubular structure, such as a blood vessel, lymphatic duct, intestine, etc. According to the invention, the applicator 1 comprises a tubular shell 2, at least two end caps 4 and 6, all of which define a lumen 7 for exposing fluid to the vessel 14. The applicator 1 is able to accommodate (and can comprise) a fluid influent means 8 and a fluid effluent means 10 for introduction and evacuation of fluids into and out of the lumen 7, respectively.

The shell 2 can be shaped to receive a variety of vessels. As is depicted in Figure 1 , the shell 2 is shaped as a generally linear tube having opposite proximal and distal ends 3 and 5. As depicted in Figures 6a and 6b, the shell 61 can be curved (Figure 6a) for receiving a curved vessel or forked for receiving a bifurcated vessel (Figure 6b). Of course, when the vessel is forked, it has more than two ends 62a, 62b, and 62c. Again referring to Figure 1, the shell 2 is not continuous in that it has a longitudinal slit 12 for receiving the vessel 14 when the applicator 1 is in the unsealed position. The boundaries of the slit 12 are defined by opposite edges 13a and 13b. As is depicted in Figure 2, when the applicator 1 is in the sealed position about the vessel, the edges 13a and 13b sealably engage each other to form a seam 16.

The seam 16 thus formed should be sufficiently tight to prevent fluid from leaking into or out of the lumen 7, and the seam 16 preferably is a watertight or hermetic seal. To ensure a proper seal, the edges 13a and 13b can have means for sealing the seam 16 when the applicator 1 is in the sealed position. In some embodiments, the means for sealing can be a function of the material from which the shell 2 is constructed, for example, electrostatic or adhesive gripping of one edge 13a by the other edge 13b. In other embodiments, such means comprise surface contour modifications having a gripping structure, for example, as are commonly employed in zip-sealing plastic bags and other containers. Another example of a gripping structure 26 is indicated in Figures 3a and 3b. To enable the applicator 1 to be removed, however, such means should not prevent the seam 16 from being readily unsealed. As is depicted in Figures 1 and 2, the applicator 1 has end caps 4 and 6, respectively disposed at each end 3 and 5. The end caps 4 and 6 are associated with the shell 2 in a manner appropriate to prevent fluid from leaking into or out of the lumen 7. Thus, the end caps 4 and 6 can be chemically bonded or adhered to the shell 2, welded to the shell 2, or the entire structure of the shell 2 and end caps 4 and 6 can be a unibody construction. Of course, where the shell has more than one end (e.g., the forked configuration depicted in Fig. 6b), the applicator can have more then two end caps. For sealably engaging the vessel 14 when the applicator 1 is in the sealed position (Figure 2), each end cap 4 and 6 has a hole 18a and 18b. Each hole 18a and 18b is appropriately sized to engage the vessel 14 with enough compressive force to form a seal sufficiently tight to prevent fluid from leaking between the applicator 1 and the vessel 14 under conditions of use. However, each hole 18a and 18b is sized so as not to apply force to the vessel 14 sufficient to collapse the vessel 14. Each hole 18a and 18b can be located in any desired axial position of the end cap 3 and 6; however, to ensure that the vessel 14 is adequately exposed to the fluid during use, the holes 18a and 18b preferably are in an off-centered axial position.

Each end cap 4 and 6 has a radially-extending passage 20a and 20b for receiving the vessel 14 when the applicator 1 is in the unsealed position. The radial passages 20a and 20b are contiguous with the holes 18a and 18b and the slit 12 so that the entire applicator 1 can be placed around a desired portion of the vessel. As is depicted in Figure 2, the radial passages 20a and 20b form a junction 22a and 22b contiguous with the seam 16 when the applicator 1 is in the sealed position. Each junction 22a and 22b thus formed should be sufficiently tight to prevent fluid from leaking into or out of the lumen 7, and each junction 22a and 22b preferably is a watertight or hermetic seal. To ensure a proper seal, the edges 21a-21d of the radial passages 20a and 20b can have means for sealing the respective junctions 22a and 22b when the applicator 1 is in the sealed position. The end caps 4 and 6 can be of any suitable shape or dimension to sealably engage the vessel 14 when the applicator 1 is in the sealed position. Thus, the end caps 4 and 6 can be flush with the ends 3 and 5 (see, e.g., Figure 1), or shaped (e.g., tapered) to facilitate observation of the vessel 14 within the applicator 1 (see, e.g., Figure 4).

To prevent fluid from leaking into or out of the lumen 7, the shell 2 and the end caps 4 and 6 are constructed from material at least substantially impervious to fluid flow. Furthermore, for use during medical procedures, they should be constructed of non-toxic material. Also, the material from which they are constructed preferably does not react with tissue or body fluids of the patient or fluids placed within the applicator 1 for delivery to the patient. To observe the vessel 14 within the applicator 1 and to monitor the delivery of fluid to the vessel 14, the shell 2 is most preferably transparent, as can be the end caps 4 and 6. While many materials having these desired qualities are known in art, the shell 2 is advantageously constructed from silastic tubing, such as commonly employed in medical devices is a preferred material. For sealably engaging the vessel 14, the end caps 4 and 6 preferably are formed from pliant but resilient material, such as silicone sealant (e.g., CLEAR SILICONE SEALER, manufactured by Loctite Corp.). The applicator 1 can accommodate an influent means 8 and an effluent means 10 for introduction and evacuation of fluids into and out of the lumen 7, respectively. The influent means 8 and effluent means 10, thus, permit fluid communication between the lumen 7 and remote fluid sources (e.g., pumps, syringes, etc.) without compromising the fluid barrier between the lumen 7 and the space immediately outside the applicator 1 formed by the shell 2 and end caps 4 and 6.

The influent means 8 and effluent means 10 are any structures appropriate to deliver fluid into and out of the lumen 7. For example, as depicted in Figure 1, the influent and effluent means 8 and 10 can be narrow tubing (e.g., a needle, a catheter, a cannula, etc.). In some embodiments, the influent and effluent means 8 and 10 are integral with the shell 2 or the end caps 4 and 6. However, the influent and effluent means 8 and 10 need not be integral with the applicator. For example, the influent and effluent means 8 and 10 can be slipped through the seam 16 or a junction 22a or 22b into fluid communication with the lumen 7. Where the influent and effluent means 8 and 10 are a needle, it can puncture the shell 2 or the end caps 4 and 6 without causing fluid to leak from the lumen. While the influent means 8 and effluent means 10 are depicted in Figure 1 as separate structures, the influent means 8 can be or comprise the same structure as the effluent means 10.

The applicator can be constructed by any suitable method. For example, where the shell and end caps are a unibody or integral structure, the applicator can be molded into the desired shape by standard methods. Another method of constructing the applicator is depicted in Figures 5a-5c. According to this method, a strip of suitable material to form the shell 51 is first obtained (e.g., a silastic tube with a longitudinal slit). Secondly, end caps 52a and 52b are formed by depositing a suitable sealant (e.g., clear silicone sealant) at the ends 53a and 53b of the tubing (Figure 5b). A tube 54 approximating the diameter of the vessel is placed within the deposits of sealant 52a and 52b to form holes 55a and 55b for accommodating a vessel. After a period of time, the deposits of sealant 52a and 52b set, forming fluid tight bonds with the shell 51. After the deposits of sealant 52a and 52b set (Figure 5c), the end caps are completed by cutting through deposits of sealant 52a and 52b to form radial passages 56a and 56b for accommodating the vessel, and they are further trimmed to the desired shape.

The operation of the applicator is depicted in Figures 1 and 2. In the unsealed position (Figure 1), the applicator 1 is deployed over the vessel 14 by sliding the vessel 14 through the slit 12 and radial passages 20a and 20b of the end caps 4 and 6. When properly in place, the vessel 14 rests within the holes 18a and 18b of each end cap 4 and 6. At such time, the applicator 1 is moved to the sealed position (Figure 2) by pressing the edges 13a and 13b of the slit 12 together such that they sealably engage each other, forming the seam 16. Pressure can also be applied to the end caps 4 and 6, such that the radial passages 20a and 20b close to form junctions 22a and 22b contiguous with the seam 16. The closure of the applicator 1 constricts the holes 18a and 18b sufficiently to sealably engage the vessel 14.

From the description above, it will be apparent that when the applicator 1 is in the sealed position (Figure 2) around a vessel 14, the lumen 7 is segregated from fluid contact with the space immediately outside the applicator 1 (e.g., the bodily fluids of a patient). At such time, fluids or semifluids (e.g., solutions, gels, magmas, etc.) can be supplied to the region of the vessel 14 within the lumen 7 via the influent means 8. Such fluids or semifluids applied to the desired region of the vessel 14 can contain any desired medicament or substance to supply to the vessel (e.g., antibodies, drugs, viruses, plasmids, etc.). After a desired period of time, the fluids can be evacuated from the lumen 7 through the fluid effluent means 10.

All of the references cited herein, including patents, patent applications, and publications, are hereby incorporated in their entireties by reference.

While this invention has been described with an emphasis upon preferred embodiments, it will be obvious to those of ordinary skill in the art that variations of the preferred embodiments may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the following claims.

Claims

WHAT IS CLAIMED IS:

1. A non-occlusive applicator for coaxially receiving and enclosing a vessel, said applicator comprising a tubular shell with at least two ends, wherein said applicator can be resiliently moved between an unsealed position and a sealed position, said shell has a longitudinal slit for receiving said vessel when said applicator is in said unsealed position, said slit forming a seam when said applicator is in said sealed position, each of said ends includes an end cap having a hole sized to sealably engage said vessel when said applicator is in said sealed position, each of said end caps includes a radial passage for accommodating said vessel when said applicator is in the unsealed position, each of said radial passages being contiguous with said holes and said slit, and each of said radial passages forming a junction contiguous with said seam when said applicator is in said sealed position, and said applicator accommodates a fluid influent means and a fluid effluent means.

2. A non-occlusive applicator for coaxially receiving and enclosing a vessel, said applicator comprising: a generally tubular resilient shell having opposite longitudinal ends and a longitudinal slit therebetween, first and second end caps mounted to said shell at said opposite ends, each of said end caps having a hole for engaging said vessel and a radial passage extending between said hole and said slit.

3. A non-occlusive applicator for coaxially receiving and enclosing a bifurcated vessel, said applicator comprising: a generally tubular resilient bifurcated shell, having at least three ends and a longitudinal slit therebetween, end caps mounted to said shell at each of said ends, each of said end caps having a hole for engaging said vessel and a radial passage extending between said hole and said slit.

4. The applicator of claim 2 or 3, which can be resiliently moved between an unsealed position in which said slit and said radial passages are spread apart to receive said vessel into said holes and a closed position in which said slit closes to form a seam and in which said radial passages close to form a junction contiguous with said seam.

5. The applicator of any of claims 2-4, wherein said holes sealably engage said vessel when said applicator is in said sealed position.

6. The applicator of any of claims 2-5, wherein said shell and said end caps define an internal lumen for accommodating fluid surrounding said vessel. 7. The applicator of any of claims 2-6, which accommodates a fluid influent means.

8. The applicator of any of claims 2-7, which accommodates a fluid effluent means.

9. The applicator of any of claims 1-8, wherein said shell is constructed of silastic tubing.

10. The applicator of any of claims 1-9, wherein said shell is transparent.

11. The applicator of any of claims 1-10, wherein said slit comprises edges having means for securing a seam.

12. The applicator of any of claims 1-11, wherein said end caps comprise pliable silicone material.

13. The applicator of any of claims 1-12, wherein said end caps are transparent.

14. The applicator of any of claims 1-13, wherein said end caps are tapered.

7. The applicator of any of claims 3-6, wherein said shell and said end caps define an internal lumen for accommodating fluid surrounding said vessel.

8. The applicator of any of claims 3-7, which accommodates a fluid influent means.

9. The applicator of any of claims 3-8, which accommodates a fluid effluent means.

10 The applicator of any of claims 1-9, wherein said shell is constructed of silastic tubing.

11. The applicator of any of claims 1-10, wherein said shell is transparent.

12. The applicator of any of claims 1-11, wherein said slit comprises edges having means for securing a seam.

13. The applicator of any of claims 1-12, wherein said end caps comprise pliable silicone material.

14. The applicator of any of claims 1-13, wherein said end caps are transparent.

15. The applicator of any of claims 1-14, wherein said end caps are tapered.