阅读说明：本技术 用于粘膜下组织分离的系统和方法 (Systems and methods for submucosal tissue separation ) 是由 肖恩·赖安 塞缪尔·雷宾 马修·B·霍利尔 于 2018-05-18 设计创作，主要内容包括：本发明总体上涉及医疗装置的领域并且具体地涉及用于在胃肠(GI)道内切除恶性和癌前病变的内窥镜系统和方法。特别地，本发明涉及用于输送在组织层之间(例如，在肌层和粘膜下层之间)的可注射组合物以抬升和稳定病变以便快速及有效切除的系统和方法。(The present invention relates generally to the field of medical devices and in particular to endoscopic systems and methods for removing malignant and pre-cancerous lesions in the Gastrointestinal (GI) tract. In particular, the present invention relates to systems and methods for delivering an injectable composition between tissue layers (e.g., between the muscular layer and submucosa) to elevate and stabilize lesions for rapid and efficient ablation.)

1. A system, comprising:

a delivery device comprising a proximal portion, a distal portion, and a lumen extending therebetween;

a first injectable composition disposed within the distal portion of the delivery device; and

a second injectable composition disposed within the proximal portion of the delivery device;

wherein the viscosity of the first injectable composition is less than the viscosity of the second injectable composition.

2. The system of claim 1, wherein the first and second injectable compositions do not substantially mix within the cavity of the delivery device.

3. The system of any one of claims 1-2, wherein the first and second injectable compositions are separated by a barrier member.

4. The system of claim 3, wherein the blocking member is configured to rupture at a force above a threshold level.

5. The system of any one of claims 3 to 4, wherein the barrier member comprises a biocompatible or biodegradable material.

6. The system of any one of claims 1-5, wherein the viscosity of the second injectable composition is at least ten times greater than the viscosity of the first injectable composition.

7. The system according to any one of claims 1 to 6, wherein the second injectable composition comprises a hydrophilic polymer selected from the group consisting of acrylate-based polymers, polyurethane-based polymers, polynorbornene-based polymers, and polylactide-based polymers.

8. The system of claim 7, wherein the hydrophilic polymer further comprises a polysaccharide.

9. The system of claim 8, wherein the polysaccharide is xanthan gum.

10. The system of any one of claims 1 to 9, wherein the delivery device comprises a sharpened distal end.

11. The system of any one of claims 1-10, wherein the delivery device is configured to be delivered through a working channel of an endoscope.

12. The system of any one of claims 1-11, wherein the volume of the first injectable composition in the delivery device is less than the volume of the second injectable composition in the delivery device.

13. A system, comprising:

a first delivery device comprising a first injectable composition; and

a second delivery device comprising a second injectable composition;

wherein the viscosity of the first injectable composition is less than the viscosity of the second injectable composition.

14. The system of claim 13, wherein the viscosity of the second injectable composition is at least ten times greater than the viscosity of the first injectable composition.

15. The system according to any one of claims 13 to 14, wherein the second injectable composition comprises a hydrophilic polymer selected from the group consisting of acrylate-based polymers, polyurethane-based polymers, polynorbornene-based polymers, and polylactide-based polymers.

Technical Field

The present invention relates generally to the field of medical devices and in particular to endoscopic systems and methods for removing malignant and pre-cancerous lesions in the Gastrointestinal (GI) tract. In particular, the present invention relates to systems and methods for delivering injectable compositions between tissue layers (e.g., between the muscular and submucosal layers) to separate, elevate, and stabilize lesions for rapid and efficient ablation.

Background

Examples of the use of injectable compositions in medical devices to separate one structure from another in order to separate, elevate and/or stabilize a first structure to perform diagnostic or therapeutic steps safely, quickly and efficiently are known. For example, endoscopic procedures, such as Endoscopic Mucosal Resection (EMR), Endoscopic Submucosal Dissection (ESD), colonic polypectomy, and anal endoscopic myotomy (POEM), are commonly performed to detect and remove malignant and precancerous lesions, tumors, and/or other unhealthy tissue within the mucosa and submucosa of the Gastrointestinal (GI) tract. In order to reduce the risk of perforation of the GI tract, it is important to separate the submucosa from the underlying muscularis before performing the resection or dissection procedure. A common method of establishing such separation is to inject a low viscosity fluid between the muscle layer and the submucosal tissue layer. However, these low viscosity fluids tend to dissipate within the surrounding tissue, and thus may not adequately lift/elevate submucosa throughout the procedure. While high viscosity fluids can provide the necessary lifting of submucosa, their inability to flow between layers of tissue requires high injection forces that tend to damage and/or penetrate the layers of tissue.

Various beneficial medical results may be achieved by the systems and/or methods of the present invention, which combine the tissue separation capability of low viscosity fluids with the tissue lifting and stabilizing capability of high viscosity fluids.

Disclosure of Invention

The present invention, in its various aspects, provides systems and methods for delivering an injectable composition between tissue layers (e.g., between the muscular and submucosal layers) to separate, elevate, and stabilize the tissue layers for effective visualization and/or ablation. The injectable compositions disclosed herein can be introduced between any two adjacent tissue or muscle layers that require separation, as well as in regions of the body outside of the GI tract (e.g., uterus, bladder, etc.).

In one aspect, the present invention is directed to a system comprising a delivery device including a proximal portion, a distal portion, and a lumen extending therebetween. The first injectable composition may be disposed within a distal portion of the delivery device and the second injectable composition may be disposed within a proximal portion of the delivery device. The viscosity of the first injectable composition may be less than the viscosity of the second injectable composition. For example, the viscosity of the second injectable composition may be at least ten times the viscosity of the first injectable composition. The first and second injectable compositions may not substantially mix within the lumen of the delivery device. The first and second injectable compositions may be separated by a barrier member. The blocking member may be configured to rupture at a force above a threshold level. The barrier member may comprise a biocompatible or biodegradable material. The second injectable composition may include a hydrophilic polymer including, as non-limiting examples, acrylate-based polymers, polyurethane-based polymers, polynorbornene-based polymers, and polylactide-based polymers. The hydrophilic polymer may include a polysaccharide including, as a non-limiting example, xanthan gum. The delivery device may include a sharpened distal end. The delivery device may be delivered through a scope, sheath, or catheter-based instrument, which includes, by way of non-limiting example, the working channel of an endoscope or colonoscope, among others.

In another aspect, the invention relates to a system comprising a first delivery device loaded with a first injectable composition and a second delivery device loaded with a second injectable composition. The viscosity of the first injectable composition may be less than the viscosity of the second injectable composition. For example, the viscosity of the second injectable composition may be at least ten times the viscosity of the first injectable composition. The second injectable composition may include a hydrophilic polymer including, as non-limiting examples, acrylate-based polymers, polyurethane-based polymers, polynorbornene-based polymers, and polylactide-based polymers. The hydrophilic polymer may include a polysaccharide including, as a non-limiting example, xanthan gum. The first and/or second delivery devices may include a sharpened distal end. The first and/or second delivery devices may be delivered through a scope, which includes, as non-limiting examples, the working channel of an endoscope or colonoscope.

In another aspect, the invention relates to a method for resecting tissue comprising: positioning a portion of a delivery device between adjacent first and second tissue layers, delivering a first injectable composition through a lumen of the delivery device into a region between the adjacent first and second tissue layers such that at least a portion of the first and second tissue layers are separated, delivering a second injectable composition through a lumen of the delivery device into the separation between the first and second tissue layers created by the first injectable composition and ablating at least a portion of the first tissue layer. The delivery device may include a proximal portion, a distal portion, and a lumen extending therebetween. The viscosity of the first injectable composition may be less than the viscosity of the second injectable composition. The second injectable composition may lift or elevate the first tissue layer above the second tissue layer. The first tissue layer may comprise a submucosal tissue layer. The second tissue layer may comprise a muscularis tissue layer. The submucosal tissue layer can include lesions.

Drawings

Non-limiting embodiments of the present invention are described by way of example with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every drawing, nor is every component of each embodiment of the invention shown as necessary to allow those of ordinary skill in the art to understand the invention. In the drawings:

fig. 1 provides a perspective view of an injectable composition filled delivery device according to one embodiment of the present invention.

Figures 2A to 2D show representative steps of a submucosal tissue removal procedure in accordance with one embodiment of the present invention.

It is noted that the drawings are only intended to depict typical or exemplary embodiments of the invention. It is also noted that the drawings may not necessarily be to scale. Accordingly, the drawings should not be considered as limiting the scope of the invention. The invention will now be described in more detail with reference to the accompanying drawings.

Detailed Description

Before the present invention is described in further detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope beyond the appended claims. Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Finally, while embodiments of the present invention have been described with particular reference to the use of an endoscope to deliver injectable compositions between tissue layers of the GI tract (e.g., between the muscular and submucosal layers) to separate and lift the tissue layers for effective visualization and/or ablation, it should be understood that various delivery systems (e.g., guide lumens, catheters, ports, etc.) inserted into various lumens of a patient may also be used to deliver such injectable compositions.

As used herein, the term "injectable composition" includes any sterile, flowable and biologically inert fluid that can be introduced between tissue layers of a patient. In various embodiments, the injectable compositions may comprise a suitable hydrophilic polymer mixed or dissolved in an aqueous solution. For example, the hydrophilic polymer may include a polysaccharide (e.g., xanthan gum, gellan gum, chitosan, cellulose, amylose, pectin, alginate, hyaluronic acid, and salts or derivatives thereof) dissolved in isotonic physiological saline. Polysaccharides for use in connection with the present invention may vary widely in molecular weight ranging, for example, from 5kDa or less to 20,000 or more. The viscosity of these injectable compositions can vary, depending on the particular requirements of the medical procedure, by increasing or decreasing the concentration of the polysaccharide. As discussed in more detail below, the injectable compositions of the present invention may be provided in and delivered from a syringe, needle, or other suitable delivery device.

As used herein, the term "viscosity" relates to the degree to which a fluid resists flow under an applied force. The addition of a given polysaccharide to an aqueous solution results in an increase in the viscosity of the solution. Solution viscosity is a function of polymer concentration and polymer molecular weight. At a given constant weight concentration, the viscosity of the solution is generally exponential to the molecular weight of the polymer used to adjust the viscosity of the solution. Thus, an increase in the molecular weight of a given polymer will allow a lower concentration (by weight) of polymer to be used to achieve a given viscosity, while a decrease in the molecular weight of a given polymer will allow a higher concentration (by weight) of polymer to be used to achieve a given viscosity.

As used herein, the term "distal" refers to the end that is furthest from the medical professional when the device is introduced into a patient, while the term "proximal" refers to the end that is closest to the medical professional when the device is introduced into a patient.

As used herein, the terms "resecting," "dissecting," and grammatical equivalents thereof include removing a tissue lesion and/or tumor from surrounding healthy tissue using various tissue cutting techniques known in the art. By way of non-limiting example, such cutting techniques may include electrocautery-based tissue cutting elements and/or tissue cutting elements that include sharp surfaces (i.e., knives, scalpels, scissors, etc.).

In various embodiments, the present invention is generally directed to systems and methods for separating and lifting submucosal tissue layers from the underlying muscle layers for safe and effective visualization and/or ablation of tissue lesions. In one embodiment, a tissue resection procedure of the present invention may include the steps of: 1) positioning an endoscope within a lumen of a patient adjacent to a known or suspected tissue lesion, 2) advancing a delivery device through a working channel of the endoscope such that a sharpened distal end of the delivery device penetrates a tissue wall of the lumen and is located between a muscular layer and a submucosal layer, 3) delivering a first (e.g., low viscosity) injectable composition between the muscular layer and the submucosal tissue layer to separate tissue layers, 4) delivering a second (e.g., high viscosity) fluid into a space created by the first injectable composition to lift (e.g., lift) the submucosal layer from the underlying muscular layer, and 5) resecting the tissue lesion using a tissue cutting element disposed within the working channel of the endoscope.

Referring to fig. 1, in one embodiment, the injectable composition delivery device 100 of the present invention may include a proximal portion 112, a distal portion 114, and a lumen 116 extending therebetween. The distal portion 114 of the delivery device 100 may be filled with a first (e.g., low viscosity) injectable composition 120 and the proximal portion 112 of the delivery device 100 may be filled with a second (e.g., high viscosity) injectable composition 122. In various embodiments, the first injectable composition can include a viscosity range (e.g., a viscosity of about 0.0 centipoise (cP) to a viscosity of about 10.0cP or greater). Similarly, the second injectable composition may include a viscosity range that is about 10 times (e.g., about 100.0cP) the viscosity of the first injectable composition. The high viscosity second injectable composition 122 may include, as non-limiting examples, gellan gum or other substances that form a pseudo-solid gel at room temperature. In one embodiment, gellan gum may be mixed with an isotonic aqueous solution (e.g., physiological saline, etc.) to a final concentration of about 0.10% at room temperature and dissolved by heating the solution to about 70 ℃. Upon cooling to about 40 ℃, the solution may solidify into a brittle injectable gel that resists mixing with the first (e.g., low viscosity) injectable composition. In one embodiment, the first injectable composition 120 may include a low concentration of gellan gum of the second injectable composition dissolved in the same or a different isotonic aqueous solution. Alternatively, the first injectable composition may not include any amount (e.g., 0.0%) of gellan gum. A plunger 119 may be slidably disposed within the lumen 116 of the delivery device 100 to sequentially deliver the first and second injectable compositions 120, 122 through an opening 115a on the distal end 115 of the delivery device 100 as the plunger 119 is advanced distally. In one embodiment, the semi-solid nature of the second injectable composition 122 may prevent mixing of the first and second injectable compositions when the plunger is advanced distally. Additionally or alternatively, the first and second injectable compositions 120, 122 may be separated by a barrier member 126. In one embodiment, the barrier member can be formed of a breakable membrane configured to break after the first injectable composition 120 has been expelled from the distal portion of the delivery device 100. By way of non-limiting example, the blocking member 126 may be formed from a high concentration of gellan gum or other suitable biocompatible or biodegradable material (as known in the art).

Although fig. 1 depicts a delivery device 100 comprising unequal volumes of the first and second injectable compositions 120, 122, in various embodiments, the relative amounts (e.g., volumes) of the first and second injectable compositions 120, 122 can vary. Additionally or alternatively, the delivery device 100 may include different arrangements of the first and second injectable compositions 120, 122. For example, the delivery device 100 may be loaded with two or more portions of the second injectable composition 122, each of which may be separated by a separate portion of the first injectable composition 120 and/or the barrier member 126. This alternating arrangement of the first and second injectable compositions 120, 122 may allow a medical professional to sequentially resect or exfoliate multiple tissue lesions and/or sequentially resect separate portions of a single large lesion, as discussed below. Additionally or alternatively, the systems and methods of the present invention are not limited to first and second injectable compositions having different viscosities, but may include any number of injectable compositions having different viscosity ranges. In various embodiments, the devices and methods of the present invention are not limited to injectable compositions loaded within a single delivery device, but may include two or more delivery devices (e.g., arranged in series or as separate delivery devices), wherein each delivery device is loaded with a different injectable composition.

Referring to fig. 2A, in use and by way of example, an endoscope 130 may be positioned within a lumen 140 of the GI tract adjacent to a known or suspected tissue lesion 144 within a submucosa 142. Endoscope 130 may include a distal end 132, a proximal end (not shown), and a working channel 134 extending therebetween. The distal end 132 of the endoscope 130 may include a camera 136 to visualize the working area and to assist the medical professional in navigating within the tortuous anatomy of the GI tract. Various extendable/retractable medical instruments, including, for example, delivery device 100 and/or tissue cutting element 138 (e.g., fig. 2D) may extend through working channel 134 to manipulate tissue beyond the distal end of the endoscope. As evidenced by the proximity of the tissue lesion 144 to the muscularis layer 146, resecting the tissue lesion 144 without lifting and separating the submucosa 142 from the underlying muscularis layer 146 would be technically challenging, i.e., very time consuming and very likely to penetrate the muscularis layer.

Referring to fig. 2B, the distal end 115 of the delivery device 100 may include a tip configured to penetrate the submucosa 142 and position the opening 115a of the delivery device 100 between the submucosa 142 and the muscularis tissue layer 146. The first injectable composition 120 can then be advanced through the distal portion 114 of the delivery device 100 to flow between and separate the submucosa 142 and the underlying muscularis layer 146. In various embodiments, the amount (e.g., volume) of the first injectable composition 120 delivered between tissue layers can vary depending on the size, shape, and/or location of the tissue lesion.

Referring to fig. 2C, with the submucosa 142 and muscularis tissue layer 146 sufficiently separated, the second injectable composition 122 can be advanced through the proximal portion 112 and distal portion 114 of the delivery device 100 into the space created by the first injectable composition. Because the submucosa 142 and the muscularis tissue layer 146 have been separated by the first injectable composition, the second injectable composition 122 can be delivered with significantly reduced force between the tissue layers, thereby minimizing the likelihood of causing tissue trauma and/or perforation. In addition, the second injectable composition 122 cannot flow into or between the unseparated portions of the submucosa 142 and muscularis tissue layer 146, and thus can provide an outward radial force that lifts the submucosa 142 (and the tissue lesion 144 therein) from the underlying muscularis layer 146 to form a protrusion or "bleb". As described above, the amount (e.g., volume) and/or viscosity of the second injectable composition 122 can vary depending on the size, shape, and/or location of the tissue lesion.

Referring to fig. 2D, tissue cutting element 138 may then be deployed through the working channel of the endoscope to resect tissue lesion 144 along its edge. In various embodiments, the protuberance or "bleb" may improve the ability of a medical professional to visualize tissue lesion 144 and/or provide a space or cushioning area to minimize the possibility of accidental cuts into muscle layer 146. In addition, the radial force exerted by the second injectable composition may also place the tissue lesion 144 and surrounding healthy tissue under constant and consistent pressure to minimize movement of the tissue lesion 144 (e.g., to immobilize it) and/or to provide a solid surface against which the tissue cutting element 138 may exert a force to effect precise resection along the edge of the tissue lesion. Alternatively, where the tissue lesion can extend into (e.g., invade) the muscle layer 146, the medical professional can see that the tissue layer cannot be separated by the second injectable composition, identifying a lesion that a standard resection cannot treat.

Although embodiments of the present invention are described with reference to endoscopic procedures performed in the GI tract, such as Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD), embodiments of the present invention may also be used in other suitable endoscopic procedures, or in procedures other than endoscopic procedures, such as urological procedures, orthopedic procedures, or open invasive procedures. Furthermore, embodiments of the present invention may be applied to many parts of the body other than the GI tract.

In accordance with the present invention, all of the systems and/or methods disclosed and claimed herein can be made and executed without undue experimentation. While the system and method of the present invention has been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the system and/or method and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.