Lymphatic Conduction System Implant

Abstract

This application relates to a lymphatic conduction system implant (10) comprising a stent graft (12) and a porous membrane (14). The stent graft has a non-porous tubular sidewall (16) with a proximal end (18) and a distal end (20). The non-porous tubular sidewall is arranged to define a lumen having an inflow port (24) at the proximal end (18) and an outflow port (26) at the distal end (20). All exposed surfaces of the stent graft are made of a first biocompatible material. The porous membrane (14) is connected to the proximal end of the non-porous tubular sidewall of the stent graft and is arranged to span the entire transverse area of the inflow port of the lumen of the stent graft. The porous membrane is made of a second biocompatible material. In a preferred embodiment, the porous membrane (14) is provided as a drug-eluting porous membrane carrying a drug.

Description

[0001] Cross - reference to related applications

[0002] None. Technical field

[0003] The present invention relates to a device for a patient's lymphatic system, and more particularly, to a lymphatic conduction system implant and a method of using the same. Background art

[0004] When cancer metastasizes from a primary tumor to surrounding tissues, cancer cells often become trapped within a patient's lymph nodes. Thus, a physician can dissect one or more lymph nodes, thereby having the diagnostic advantage of knowing whether and to what extent the cancer has metastasized from the surrounding tissues. However, there can be adverse effects associated with lymph node dissection, including but not limited to predisposing the patient to infection, lymphedema, edema, or seroma.

[0005] There is a need in the art for a device that helps eliminate the adverse effects after lymph node dissection by assisting in restoring proper conduction of lymphatic fluid at the lymph node dissection site. Summary of the invention

[0006] The present invention provides a device that helps eliminate the adverse effects after lymph node dissection by assisting in restoring proper conduction of lymphatic fluid at the lymph node dissection site.

[0007] In one form, the present invention relates to a lymphatic conduction system implant that includes a stent - graft and a porous membrane. The stent - graft has a non - porous tubular sidewall. The non - porous tubular sidewall has a proximal end and a distal end. The non - porous tubular sidewall is configured to define a lumen that has an inflow port at the proximal end and an outflow port at the distal end. All exposed surfaces of the stent - graft are made of a first biocompatible material. The porous membrane is connected to the proximal end of the non - porous tubular sidewall of the stent - graft. The porous membrane is configured to span the entire transverse area of the inflow port of the lumen of the stent - graft. The porous membrane is made of a second biocompatible material.

[0008] In another form, the present invention relates to a lymphatic conduction system implant that includes a stent - graft, a drug - eluting porous membrane, and a drug. The stent - graft has a non - porous tubular sidewall. The non - porous tubular sidewall has a bottom lymphatic region end and an upper lymphatic region end. The non - porous tubular sidewall is configured to define a lumen that has an inflow port at the bottom lymphatic region end and an outflow port at the upper lymphatic region end. All exposed surfaces of the stent - graft are made of a first biocompatible material. The drug - eluting porous membrane is connected to the bottom lymphatic region end of the non - porous tubular sidewall of the stent - graft. The drug - eluting porous membrane is configured to span the entire transverse area of the inflow port of the lumen of the stent - graft. The drug - eluting porous membrane is made of a second biocompatible material. The drug is carried by the drug - eluting porous membrane.

[0009] One advantage of the present invention is that the lymphatic conduction system implant helps to eliminate the adverse effects after lymph node dissection by assisting in restoring the proper conduction of lymphatic fluid in the lymph node anatomical site.

[0010] Another advantage is that the drug-eluting porous membrane can provide local and / or systemic drug delivery with sustained / extended release. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The above and other features and advantages of the present invention and the manner of achieving them will be made apparent by reference to the following description of embodiments of the invention in conjunction with the accompanying drawings, and the invention will be better understood, in which:

[0012] Figure 1 is a perspective view of a lymphatic conduction system implant according to an aspect of the present invention;

[0013] Figure 2 is Figure 1 of the lymphatic conduction system implant along Figure 1 a cross-sectional view taken along plane 2-2-2-2; and

[0014] Figure 3 is a view of a lymphatic conduction system implant according to an aspect of the present invention positioned in the lymphatic vessels of the lymphatic system Figure 1 and 2 of.

[0015] In all the drawings, corresponding reference numerals represent corresponding parts. The examples set forth herein represent at least one embodiment of the present invention, and these examples should not be construed as limiting the scope of the present invention in any way. DETAILED DESCRIPTION

[0016] Reference is now made to the drawings, and more particularly to Figure 1 and 2 which show a lymphatic conduction system implant 10 according to an aspect of the present invention.

[0017] The lymphatic conduction system implant 10 includes a stent graft 12 and a porous membrane 14. The stent graft 12 has a non-porous tubular sidewall 16. The non-porous tubular sidewall 16 has a proximal end 18 and a distal end 20. Functionally, the proximal end 18 may also be described herein as the bottom lymphatic vessel region end 18 of the lymphatic conduction system implant 10, and the distal end 20 may also be described herein as the upper lymphatic vessel region end 20 of the lymphatic conduction system implant 10.

[0018] The non-porous tubular sidewall 16 can be in the form of a polymeric tubular member that defines a lumen 22 having an inflow port 24 at a proximal end 18 and an outflow port 26 at a distal end 20. The cross-sectional shape of the polymeric tubular member and the lumen 22 can be, for example, circular or elliptical. The diameter of the stent graft 12 can be an approximation of the diameter of the lymphatic vessel into which the lymphatic conduction system implant 10 will be inserted, for example, having a diameter in the range of 0.2 millimeters (mm) to 2 mm, so as to provide a tight fit within the lymphatic vessel.

[0019] All exposed surfaces of the stent graft 12 are made of a first biocompatible material, such as expanded polytetrafluoroethylene (ePTFE). In the present embodiment, the non-porous tubular sidewall 16 comprises ePTFE. For example, the non-porous tubular sidewall 16 of the stent graft 12 comprises an ePTFE coating. For example, the ePTFE coating can be used to achieve the non-porous nature of the non-porous tubular sidewall 16.

[0020] The porous membrane 14 can be connected to the proximal end 18 of the non-porous tubular sidewall 16 of the stent graft 12, for example, by ultrasonic or other welding, heat melt adhesives, or overmolding. Optionally, the porous membrane 14 can be formed by directly electrospinning onto the surface of a polymeric sheet, wherein the polymeric sheet can be attached to the stent graft 12 (e.g., by heat melt adhesives, direct wire attachment, or overmolding) before or after electrospinning the porous membrane 14 onto the surface of the polymeric sheet.

[0021] The porous membrane 14 is sized and shaped to span the entire lateral area of the inflow port 24 of the lumen 22 of the stent graft 12. The porous membrane 14 can have a thickness, for example, in the range of 50 nanometers (nm) to 100 nm. The porous membrane 14 can be made of a second biocompatible material and can also be made of a resorbable material. For example, the second biocompatible material of the porous membrane 14 can wholly or partially comprise polyglycolide or polyglycolic acid (PGA) or poly(lactic-co-glycolic) acid (PLGA). In the present embodiment, the porous membrane 14 is an electrospun fiber mesh that is connected to the proximal end 18 of the non-porous tubular sidewall 16 of the stent graft 12, for example, by one of the above-described connection methods.

[0022] Optionally, the porous membrane 14 can be provided as a drug-eluting porous membrane that bears a drug. The drug can be, for example, an antibacterial drug, a chemotherapeutic drug, and / or an anti-metastatic drug. The drug can be impregnated on and between the electrospun fibers that make up the porous membrane 14. Thus, for the purpose of drug elution selection, the porous membrane 14 can sometimes also be referred to as the drug-eluting porous membrane 14.

[0023] Also refer to Figure 3, the lymphatic conduction system implant 10 is configured to facilitate the conduction of lymphatic fluid 28 (represented as small circles in Figure 3 ) in the lymphatic vessels 30 after lymph node removal or lymph node dissection (due to cancer metastasis or other reasons). The lymphatic conduction system implant 10 can be deployed into the lymphatic system using a standard stent graft balloon system, thereby arranging the lymphatic conduction system implant 10 at the lymph node dissection site 30-1. The method used includes positioning the lymphatic conduction system implant 10 in the lymphatic vessel 30, in the lymphatic duct 32, and between the bottom (inlet) valve 34 in the bottom lymphatic duct region 32-1 (i.e., at its proximal end) and the upper (outlet) valve 36 in the upper lymphatic duct region 32-2 (i.e., at its distal end) of the lymphatic duct 32. In Figure 3 the shown orientation of the lymphatic duct 32, the bottom lymphatic duct region 32-1 can be considered the lower part (e.g., the lower half) of the lymphatic duct 32, and the upper lymphatic duct region 32-2 can be considered the upper part (e.g., the upper half) of the lymphatic duct 32. The bottom (inlet) valve 34 and the upper (outlet) valve 36 are each one-way bicuspid valves that prevent the backward drainage of lymphatic fluid 28.

[0024] The main function of the lymphatic conduction system implant 10 is to restore the conduction of lymphatic fluid 28 in order to help prevent lymphedema, seroma, or edema after lymph node dissection. More particularly, the distal end 20 (e.g., the open end) of the stent graft 12 is positioned near the upper (outlet) valve 36 in the upper lymphatic duct region 32-2, and the proximal end 18 (e.g., the covered end) of the stent graft 12 is positioned such that the porous membrane 14 faces the bottom (inlet) valve 34 in the bottom lymphatic duct region 32-1, so as to create a pressure difference and a concentration gradient when the inflow of lymphatic fluid 28 enters the bottom lymphatic duct region 32-1 at a position proximal to the lymphatic conduction system implant 10 through the junctions 40-1 (represented by curved arrows) between the endothelial cells 40 (the endothelial cells 40 are loosely stratified and form the lymphatic vessels 30), thereby allowing the lymphatic fluid 28 to flow into each lymphatic duct 32.

[0025] In this embodiment, in order to facilitate the conduction of lymphatic fluid 28, the length 42 of the lymphatic conduction system implant 10 does not exceed half of the total length 44 of the lymphatic duct 32. In other words, the length 42 of the lymphatic conduction system implant 10 does not exceed half of the distance (corresponding to the total length 44) between the bottom (inlet) valve 34 in the bottom lymphatic duct region 32-1 and the upper (outlet) valve 36 in the upper lymphatic duct region 32-2. For example, since the average length of the lymphatic duct 32 can be about 2 mm, the average length of the stent graft 12 can be approximately less than or equal to 1 mm.

[0026] Therefore, the length 42 of the lymphatic conduction system implant 10 is selected such that the upper regional wall of the upper lymphatic vessel region 32-2 can be blocked by the non-porous tubular sidewall 16 of the stent graft 12 of the lymphatic conduction system implant 10, while the lower half (the bottom lymphatic vessel region 32-1) will remain uncovered, thereby allowing the lymph fluid 28 to naturally flow into the bottom lymphatic vessel region 32-1 of the lymphatic vessel 32. This natural inflow of the lymph fluid 28 is achieved through the endothelium (a general term for the inner layer of blood vessels), which consists of a lining of single flattened epithelial cells (simple squamous epithelium) (i.e., endothelial cells 40). The endothelium has junctions 40-1 between the endothelial cells 40, which allow the interstitial lymph fluid 28 to flow into the lymphatic vessel 30 when the pressure becomes high enough (e.g., from blood capillary hydrostatic pressure), but generally do not allow the lymph fluid 28 to leak back into the interstitial space. By blocking the upper lymphatic vessel region 32-2 of the lymphatic vessel 32 and leaving the bottom lymphatic vessel region 32-1 of the lymphatic vessel 32 unobstructed, a pressure difference and a concentration gradient will be generated when the inflow of the lymph fluid 28 enters the bottom lymphatic vessel region 32-1 of the lymphatic vessel 32 through the junctions 40-1 between the endothelial cells 40.

[0027] The natural conduction of the lymph fluid 28 through the lymphatic vessel 30 is caused by the opening and closing of the one-way bottom (inlet) valve 34 in the bottom lymphatic vessel region 32-1 and the upper (outlet) valve 36 in the upper lymphatic vessel region 32-2 of the lymphatic vessel 32, where the opening and closing of the valves are mainly caused by smooth muscle contractions and secondary skeletal muscle contractions. This will additionally prevent the backward flow of the lymph fluid 28. Once the bottom (inlet) valve 34 opens, in addition to the lymph fluid 28 entering through the endothelial wall of the lymphatic vessel 30, the lymph fluid 28 will flow into the bottom lymphatic vessel region 32-1. Once the bottom lymphatic vessel region 32-1 is filled with the lymph fluid 28, the bottom (inlet) valve 34 will be forced to close due to the fluid pressure distal to the bottom (inlet) valve 34.

[0028] Because the lymph fluid 28 cannot enter the upper lymphatic region 32-2 through the endothelial wall of the lymphatic vessel 30 due to the blockage of the non-porous tubular sidewall 16 of the stent graft 12 of the lymphatic conduction system implant 10, such a blockage will create a negative pressure and / or concentration gradient between the bottom lymphatic region 32-1 and the upper lymphatic region 32-2 of the lymphatic vessel 32. Due to this difference, the lymph fluid 28 in the bottom lymphatic region 32-1 will flow through the porous membrane 14 by passive diffusion, as indicated by the straight arrow 46, and thus flow into the upper lymphatic region 32-2, creating an equilibrium within the lymphatic vessel 32. Once the lymphatic vessel 32 reaches equilibrium, pressure will begin to accumulate because the lymph fluid 28 can enter the bottom lymphatic region 32-1 (since the junction 40-1 between the endothelial cells 40 is unblocked), allowing the pressure and / or concentration gradient to accumulate and continuously diffuse through the porous membrane 14 until the upper (outlet) valve 36 yields to the pressure and / or opens through smooth muscle contraction. Once the upper (outlet) valve 36 opens, this allows the lymph fluid 28 to be fully directed into the remaining lymphatic system and subsequently the circulatory system.

[0029] The following items are also related to the present invention.

[0030] In one embodiment, the present invention relates to a lymphatic conduction system implant that includes a stent graft and a porous membrane. The stent graft has a non-porous tubular sidewall. The non-porous tubular sidewall has a proximal end and a distal end. The non-porous tubular sidewall can be arranged to define a lumen that has an inflow port at the proximal end and an outflow port at the distal end. All exposed surfaces of the stent graft are made of a first biocompatible material. The porous membrane can be connected to the proximal end of the non-porous tubular sidewall of the stent graft. The porous membrane can be arranged to span the entire transverse area of the inflow port of the lumen of the stent graft. The porous membrane can be made of a second biocompatible material, which can be different from the first biocompatible material.

[0031] In some embodiments, the second biocompatible material of the porous membrane can be a resorbable material.

[0032] In some embodiments, the second biocompatible material of the porous membrane can include PGA or PLGA.

[0033] In some embodiments, the porous membrane can be an electrospun fiber mesh.

[0034] In some embodiments, the non-porous tubular sidewall can include ePTFE.

[0035] In some embodiments, the non-porous tubular sidewall can include an ePTFE coating.

[0036] Optionally, the proximal end can be the end of the bottom lymphatic vessel region. Optionally, the distal end can be the end of the upper lymphatic vessel region. Optionally, the length of the lymphatic conduction system implant does not exceed half of the total length of the lymphatic vessel. Optionally, the length of the lymphatic conduction system implant does not exceed half of the distance between the inlet valve in the bottom lymphatic vessel region and the outlet valve in the upper lymphatic vessel region. Optionally, in some embodiments, the porous membrane can be a drug-eluting porous membrane carrying a drug.

[0037] In embodiments having a drug, the drug can be an antibacterial drug, a chemotherapeutic drug, and / or an anti-metastatic drug.

[0038] A method of using the lymphatic conduction system implant according to any one of the above embodiments of paragraphs 0029 - 0036 can promote lymphatic fluid conduction in the lymphatic vessels after lymph node removal and includes the following steps: positioning the lymphatic conduction system implant in the lymphatic vessels in the lymphatic vessel and between the inlet valve in the bottom lymphatic vessel region of the lymphatic vessel and the outlet valve in the upper lymphatic vessel region of the lymphatic vessel, wherein the distal end of the stent graft can be positioned near the outlet valve in the upper lymphatic vessel region, and the proximal end of the stent graft can be positioned such that the porous membrane faces the inlet valve in the bottom lymphatic vessel region, so as to create a pressure difference and a concentration gradient when the inflowing lymphatic fluid enters the bottom lymphatic vessel region at a position proximal to the lymphatic conduction system implant through the junctions between the endothelial cells of the lymphatic vessel.

[0039] In embodiments utilizing the method of using the lymphatic conduction system implant, the length of the lymphatic conduction system implant can not exceed half of the total length of the lymphatic vessel.

[0040] In embodiments utilizing the method of using the lymphatic conduction system implant, the length of the lymphatic conduction system implant can not exceed half of the distance between the inlet valve in the bottom lymphatic vessel region and the outlet valve in the upper lymphatic vessel region.

[0041] In any embodiment of the method of using the lymphatic conduction system implant, the method can optionally include a further step of refilling the porous membrane with an antibacterial drug, a chemotherapeutic drug, and / or an anti-metastatic drug.

[0042] In another embodiment, the present invention relates to a lymphatic conduction system implant, which has a stent graft, a drug-eluting porous membrane, and a drug. The stent graft has a non-porous tubular sidewall. The non-porous tubular sidewall can have a bottom lymphatic vessel region end and an upper lymphatic vessel region end. The non-porous tubular sidewall can be arranged to define a lumen that has an inlet port at the bottom lymphatic vessel region end and an outlet port at the upper lymphatic vessel region end. All exposed surfaces of the stent graft can be made of a first biocompatible material. The drug-eluting porous membrane can be connected to the bottom lymphatic vessel region end of the non-porous tubular sidewall of the stent graft. The drug-eluting porous membrane can be arranged to span the entire transverse area of the inlet port of the lumen of the stent graft. The drug-eluting porous membrane can be made of a second biocompatible material, which can be different from the first biocompatible material. The drug can be carried by the drug-eluting porous membrane.

[0043] In some embodiments, the second biocompatible material of the porous membrane can be a resorbable material including PGA or PLGA.

[0044] In some embodiments, the porous membrane can be an electrospun fiber mesh.

[0045] In any embodiment having a drug, the drug can be an antibacterial drug, a chemotherapeutic drug, and / or an anti-metastatic drug.

[0046] In some embodiments, the non-porous tubular sidewall can include ePTFE.

[0047] In some embodiments, the non-porous tubular sidewall can include an ePTFE coating.

[0048] A method of using the lymphatic conduction system implant according to any one of the above embodiments of paragraphs 0041 - 0046 can promote lymphatic fluid conduction in the lymphatic vessels after lymph node removal and includes the following steps: positioning the lymphatic conduction system implant in the lymphatic vessels in the lymphatic vessel and between the inlet valve in the bottom lymphatic vessel region of the lymphatic vessel and the outlet valve in the upper lymphatic vessel region of the lymphatic vessel, wherein the upper lymphatic vessel region end of the stent graft can be positioned adjacent to the outlet valve in the upper lymphatic vessel region, and the bottom lymphatic vessel region end of the stent graft can be positioned such that the drug-eluting porous membrane faces the inlet valve in the bottom lymphatic vessel region, so as to create a pressure difference and a concentration gradient when the inflowing lymphatic fluid enters the bottom lymphatic vessel region at a position proximal to the lymphatic conduction system implant through the junctions between the endothelial cells of the lymphatic vessel.

[0049] In the embodiment of paragraph 0047, which utilizes the method of using the lymphatic conduction system implant, the length of the lymphatic conduction system implant can not exceed half of the total length of the lymphatic vessel.

[0050] Although the invention has been described for at least one embodiment, the invention may be further varied within the spirit and scope of the present disclosure. Accordingly, this application will cover any variations, uses, or adaptations of the invention using its general principles. Moreover, this application will cover departures from the present disclosure that come within known or customary practice in the field to which this invention pertains and fall within the limits of the appended claims.

Claims

1. A lymphatic conduction system implant, the lymphatic conduction system implant comprising: A stent graft having a non-porous tubular sidewall with a proximal end and a distal end, the non-porous tubular sidewall defining a lumen having an inflow port at the proximal end and an outflow port at the distal end, wherein all exposed surfaces of the stent graft are made of a first biocompatible material; and A porous membrane connected to the proximal end of the non-porous tubular sidewall of the stent graft, the porous membrane spanning the entire transverse area of the inflow port of the lumen of the stent graft, the porous membrane being made of a second biocompatible material, Characterized in that the position of the porous membrane is arranged to create a pressure difference and / or concentration gradient of lymph fluid; and The diameter of the stent graft is an approximation of the diameter of the lymphatic vessel size.

2. The lymphatic conduction system implant according to claim 1, wherein: The second biocompatible material of the porous membrane is a resorbable material.

3. The lymphatic conduction system implant according to claim 1 or 2, wherein: The second biocompatible material of the porous membrane comprises PGA or PLGA.

4. The lymphatic conduction system implant according to any one of claims 1 to 3, wherein: The porous membrane is an electrospun fiber mesh.

5. The lymphatic conduction system implant according to any one of claims 1 to 4, wherein: The non-porous tubular sidewall comprises ePTFE.

6. The lymphatic conduction system implant according to any one of claims 1 to 5, wherein: The non-porous tubular sidewall comprises an ePTFE coating.

7. The lymphatic conduction system implant according to any one of claims 1 to 6, wherein: The porous membrane is a drug-eluting porous membrane carrying drugs.

8. The lymphatic conduction system implant according to claim 7, wherein: The drugs are antibacterial drugs, chemotherapeutic drugs and / or anti-metastatic drugs.

9. The lymphatic conduction system implant according to any one of claims 1 to 6, wherein: The diameter of the stent graft is in the range of 0.2 mm to 2 mm to provide a tight fit in the lymphatic vessels.

10. A lymphatic conduction system implant, the lymphatic conduction system implant comprising: A stent graft having a non-porous tubular sidewall with a bottom lymphatic vessel region end and an upper lymphatic vessel region end, the non-porous tubular sidewall defining a lumen having an inflow port at the bottom lymphatic vessel region end and an outflow port at the upper lymphatic vessel region end, all exposed surfaces of the stent graft being made of a first biocompatible material; A drug-eluting porous membrane connected to the bottom lymphatic vessel region end of the non-porous tubular sidewall of the stent graft, the drug-eluting porous membrane spanning the entire transverse area of the inflow port of the lumen of the stent graft, the drug-eluting porous membrane being made of a second biocompatible material; and Drugs carried by the drug-eluting porous membrane, Characterized in that the position of the drug-eluting porous membrane is arranged to create a pressure difference and / or concentration gradient of lymph fluid; and The diameter of the stent graft is an approximation of the diameter of the lymphatic vessel size.

11. The lymphatic conduction system implant according to claim 10, wherein: The second biocompatible material of the porous membrane is a resorbable material including PGA or PLGA.

12. The lymphatic conduction system implant according to claim 10 or 11, wherein: The porous membrane is an electrospun fiber mesh.

13. The lymphatic conduction system implant according to any one of claims 10 to 12, wherein: The drugs are antibacterial drugs, chemotherapeutic drugs and / or anti-metastatic drugs.

14. The lymphatic conduction system implant according to any one of claims 10 to 13, wherein: The non-porous tubular sidewall comprises ePTFE.

15. The lymphatic conduction system implant according to any one of claims 10 to 14, wherein: The non-porous tubular sidewall comprises an ePTFE coating.

16. The lymphatic conduction system implant according to any one of claims 10 to 15, wherein: The diameter of the stent graft is in the range of 0.2 mm to 2 mm to provide a tight fit in the lymphatic vessels.

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