阅读说明：本技术 一种用于血管病变的治疗系统及其应用 (Treatment system for vascular lesions and application thereof ) 是由 马晓辉 赫明 念国栋 夏崟 魏继昌 龚霄雁 于 2019-11-12 设计创作，主要内容包括：本发明涉及一种用于血管病变的治疗系统及其应用,所述治疗系统包括辅助成型单元、输送单元和混匀器；所述输送单元用于输送水凝胶。该治疗系统可以应用于各种类型血管病变的治疗并且具有很高的疗效,尤其是对动脉瘤、血管畸形或静脉曲张的治疗效果显著。(The invention relates to a treatment system for vascular lesions and application thereof, wherein the treatment system comprises an auxiliary forming unit, a conveying unit and a blending machine; the delivery unit is used for delivering hydrogel. The treatment system can be applied to the treatment of various vascular diseases and has high curative effect, particularly has obvious treatment effect on aneurysm, vascular malformation or varicose vein.)

1. A treatment system for vasculopathy is characterized by comprising an auxiliary forming unit, a conveying unit and a blending machine; the delivery unit is used for delivering hydrogel.

2. The treatment system of claim 1, wherein the vascular disorder comprises an aneurysm, a vascular malformation, or a varicose vein;

preferably, the aneurysm comprises an aortic aneurysm or an arterial dissection;

preferably, the vascular malformation comprises an arteriovenous fistula.

3. Therapeutic system according to claim 1 or 2, characterized in that the auxiliary shaping unit comprises any one of a balloon, a stent or a membrane material or a combination of at least two thereof, preferably a balloon and a stent combination.

4. The treatment system of claim 3, wherein the stent comprises a bare stent or a covered stent;

preferably, the scaffold has a mesh structure or a helical structure;

preferably, the stent is a biodegradable stent, a bioabsorbable stent, or a recyclable stent;

preferably, the membrane material comprises dacron, PTFE, silica gel, or polylactic acid.

5. The treatment system of any one of claims 1-4, wherein the delivery unit comprises a catheter;

preferably, the number of cavities of the catheter is 1-5.

6. The therapeutic system of any one of claims 1-5, wherein the hydrogel is prepared from raw materials comprising a monomer, a crosslinker, an initiator, and a solvent;

preferably, the hydrogel comprises a normal hydrogel, an adhesive hydrogel, a biodegradable hydrogel or a bioabsorbable hydrogel.

7. The therapeutic system of claim 6 wherein the monomer comprises any one or a combination of at least two of a diacrylate, acrylamide, acrylic acid, hyaluronic acid, lactic acid, glycolic acid, hydroxyethyl methacrylate, N-isopropylacrylamide, ethyleneimine, sodium alginate, carboxybetaine methacrylate, N' -methylenebisacrylamide, 2-hydroxyethyl methacrylate, or carboxybetaine acrylamide; preferably a combination of acrylamide and sodium alginate;

preferably, the cross-linking agent comprises any one or a combination of at least two of calcium sulfate, N' -methylenebisacrylamide, 3-mercaptopropyltrimethoxysilane, 3- (trimethoxysilyl) propyl methacrylate, 1-carboxy-N, N-dimethyl-N- (3-acrylamidopropyl) ethylamine inner salt or 1-carboxy-N-methyl-N, N-bis (2-methacryloyloxy-ethyl) methylamine inner salt; calcium sulfate and 3- (trimethoxysilyl) propyl methacrylate are preferred.

8. The therapeutic system of claim 6 or 7 wherein the initiator comprises any one or a combination of at least two of ammonium persulfate, benzoyl peroxide, benzophenone, α -ketoglutaric acid, or 2-hydroxy-4 '- (2-hydroxyethoxy) -2-methylpropiophenone, preferably 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone;

preferably, the solvent comprises any one of water, glycerol, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, tripropylene glycol or ethanol or a combination of at least two thereof; water is preferred.

9. The therapeutic system of any one of claims 6 to 8, wherein the hydrogel is prepared from raw materials further comprising adjuvants and/or adjuvants;

preferably, the auxiliary agent comprises any one or a combination of at least two of a contrast agent, a developing agent, a stabilizing agent or a medicament;

preferably, the auxiliary material comprises any one or a combination of at least two of fiber, microsphere or developing material;

preferably, the hydrogel has a gel time of 0.1 to 30 min.

10. Use of a therapeutic system according to any one of claims 1 to 9 for the manufacture of a device for the treatment of vascular pathologies.

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a treatment system for vascular lesions and application thereof.

Background

Aneurysms include aortic aneurysms, visceral aneurysms, and aneurysms located in the limbs, which refer to pathological dilatation of the aorta, exceeding 50% of normal vessel diameter; true aneurysms are 3-layer structures involving the wall of a blood vessel for vessel widening, and pseudoaneurysms are localized ruptures of an artery, formed by a blood clot or seal of adjacent tissue. Aortic aneurysms (including true aneurysms, pseudoaneurysms) have long been the most challenging procedure for aortic surgery due to their high mortality and high incidence of complications, major postoperative complications including: multiple organ failure, paraplegia, myocardial infarction, etc. With the maturity of surgical operation technology and the development of perioperative nursing and monitoring, especially the improvement of minimally invasive stent technology, the success rate of aortic aneurysm operation is greatly increased, and the incidence rate and mortality rate of postoperative complications are obviously reduced compared with the prior art.

Aortic dissection, arteriovenous fistula and vascular malformations and varicose veins are also highly dangerous refractory diseases, the arteriovenous fistula refers to abnormal passages between arteries and veins, and the blood of the arteries flows into the accompanying veins through abnormal passages, so that local vascular lesions of the fistula and hemodynamic changes of local, peripheral circulation and whole body systems of the fistula can be caused, and the fistula can be congenital or acquired due to trauma. Vascular malformations are abnormal expansions and channelling of capillaries, veins and arteries or lymphatic vessels with the histological and biological properties of normal endothelial cells. The aortic dissection refers to a state that blood in an aortic cavity enters an aortic media from an aortic intimal tear part to separate the media, and expands along the major axis direction of the aorta to form true and false separation of two aortic walls. Varicose veins refers to a superficial vasodilatory disease caused by reflux of the greater saphenous vein of the lower limb.

With the development of medical technology and medical instruments in recent years, the interventional intraluminal treatment of aortic aneurysms is becoming the main treatment mode for such diseases because of its minimal invasiveness and safety. The main method of interventional intracavity therapy is to isolate the aneurysm cavity through the covered stent so as to restore normal blood flow again, and the isolated aneurysm can be gradually thrombosed to finally achieve reconstruction of the aortic lumen structure. However, due to the influence of the vascular structures of different parts, I-shaped internal leakage is easily formed if the implantation of the covered stent with a complex vascular structure cannot be completely attached to the inner wall of a blood vessel; the branch artery is easy to cover the branch artery to cause ischemia when being implanted close to the aneurysm covered stent; the branch artery is connected with the aneurysm, supplies blood through the aneurysm, and blocks the blood flow of the branch artery to easily cause ischemia of corresponding organs or tissues when the stent covered with the film isolates the aneurysm; the branch arteries are connected to the aneurysm and the arteries can be covered with other arteries, but the implantation of the stent graft only isolates the aorta from the aneurysm cavity, the aneurysm blood is not completely blocked, and the aneurysm continues to enlarge by a backflow of branch arterial blood (type II endoleaks) over the aneurysm body. The existing treatment mode of the aortic dissection is to cover the proximal laceration of the aortic dissection to expand the true aortic cavity, but the existing treatment generally only covers the proximal laceration after the stent is implanted, the distal end, particularly the laceration close to the branch part of the visceral artery, cannot be blocked by a covered stent, so that the false aortic dissection cavity is continuously filled with blood, the diameter of the aortic dissection of most patients is gradually increased to form the aortic dissection, and the tumor body expands to a certain degree and is ruptured to bleed, so that the patients die. The existing treatment scheme of arteriovenous fistula mainly comprises the step of embolizing an arterial end leak by using a spring ring, but because no effective material is used for plugging a vein end of a treatment leak, wide and tiny arteriovenous communication vessels still exist between arteriovenous vessels, so that treatment failure is caused. At present, materials such as spring rings, hardening agents, sewage, alcohol and the like are mainly adopted for embolizing malformed vascular masses, but the embolization range is limited by embolization materials, and the whole malformed vascular masses cannot be completely filled and blocked, so that only a very limited treatment effect is achieved.

Therefore, it is very significant to develop a therapeutic system that can be applied to the above-mentioned typical vascular disorders, and that is easy to manufacture, excellent in therapeutic effect, and less in side effects and complications.

Disclosure of Invention

In view of the shortcomings of the prior art, the present invention aims to provide a therapeutic system for vascular lesions and application thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

in one aspect, the invention provides a treatment system for vascular lesions, comprising an auxiliary forming unit, a delivery unit and a blender; the delivery unit is used for delivering hydrogel.

All parts of the treatment system related to the invention are mutually matched, wherein the auxiliary forming unit establishes a passage for the blood vessel and assists the formation of hydrogel; a mixer uniformly mixes the single-component or multi-component hydrogel prepolymer; the delivery unit delivers the hydrogel to the target vessel lumen for filling. Compared with the mode of conveying the prepolymer of the hydrogel to a target position and then gelling, the uniformly-mixing device is selected to fully and uniformly mix different components of the prepolymer of the hydrogel so as to achieve a better gelling effect, and meanwhile, the phenomena that the prepolymer is not completely gelled and the mobile prepolymer diffuses due to nonuniform mixing of the different components are avoided.

The treatment system adopts hydrogel with good biocompatibility to fill the abnormal part of the blood vessel, so that the abnormal part of the blood vessel can be well adhered with the vascular tissue, further expansion of aneurysm and reverse tearing of a sandwich layer can be prevented, and the artery with possible blood backflow can be blocked; in addition, the hydrogel can be completely filled and fixedly formed according to tumor bodies with different shapes, so that residual tumor cavities caused by other filling modes are avoided, and meanwhile, the shaping and the branch artery reconstruction can be carried out according to the blood vessel shapes; meanwhile, the treatment system can be used for preparing hydrogel with similar elastic modulus according to the specific condition of a treatment part for filling, so that the recurrence rate of a diseased part is reduced, and the foreign body sensation is reduced.

Preferably, the vascular disorder comprises an aneurysm, a vascular malformation, or a varicose vein;

preferably, the aneurysm comprises an aortic aneurysm or an arterial dissection;

preferably, the vascular malformation comprises an arteriovenous fistula.

The treatment system related by the invention has wide application, can be applied to the treatment of various types of vascular lesions and has high curative effect, and can be easily adapted to aortic aneurysms, arterial dissections, vascular malformations and varicose veins with different tumor cavity shapes, which are difficult to solve by other treatment modes.

Preferably, the auxiliary forming unit comprises any one of a balloon, a stent or a membrane material or a combination of at least two of the balloon, the stent or the membrane material, such as a combination of the balloon and the stent, a combination of the stent and the membrane material, a combination of the balloon and the membrane material, and the like, preferably a combination of the balloon and the stent.

The auxiliary forming unit adopts a combination mode of a balloon and a stent, namely, the use of the stent is added on the basis of the balloon, which is a good strategy, particularly, for true aneurysm, the stent can well fix hydrogel to prevent displacement, and in addition, the use of the stent can also enable a filling part to have a better lumen shape, thereby being beneficial to blood circulation; for aortic dissection, the artificial cavity extrusion easily causes the channel of the true cavity to be too small, the hydrogel only fills the dissection, so that the further development of the artificial cavity is inhibited, but the effect of restoring the blood flow of the true cavity is not obvious, and the implantation of the stent in the true cavity can well restore the shape and blood supply of the true cavity in such cases. Thus, in the case of larger aneurysms, the use of a stent in combination with a hydrogel has a better therapeutic effect.

The stent is only used for forming a blood vessel cavity, and can reduce side effects and complications, wherein the side effects comprise inflammation, immune response, blood vessel secondary damage and the like, and the side effects are different from the conventional isolation mode of the covered stent to a tumor cavity or aortic dissection.

Preferably, the stent comprises a bare stent or a stent graft.

Preferably, the scaffold has a mesh structure or a helical structure. The scaffold with the net-shaped structure is prepared by weaving laser cutting or 3D printing.

Preferably, the stent is a biodegradable stent, a bioabsorbable stent, or a recyclable stent.

Preferably, the membrane material comprises dacron, PTFE, silica gel, or polylactic acid.

Preferably, the delivery unit comprises a catheter.

Preferably, the number of cavities of the catheter is 1-5.

Preferably, the hydrogel comprises a normal hydrogel, an adhesive hydrogel, a biodegradable hydrogel or a bioabsorbable hydrogel.

Preferably, the hydrogel is a single component or at least two components, and the hydrogels of the at least two components can be introduced after being uniformly mixed in vitro, mixed during the introduction of the hydrogel or introduced to the filling site and then mixed.

In the invention, the raw materials for preparing the hydrogel comprise a monomer, a cross-linking agent, an initiator and a solvent.

Preferably, the monomer comprises any one or a combination of at least two of diacrylate, acrylamide, acrylic acid, hyaluronic acid, lactic acid, glycolic acid, hydroxyethyl methacrylate, N-isopropylacrylamide, ethylene imine, sodium alginate, carboxybetaine methacrylate, N' -methylenebisacrylamide, 2-hydroxyethyl methacrylate or carboxybetaine acrylamide; combinations of the at least two are, for example: the combination of acrylamide and hydroxyethyl methacrylate, the combination of sodium alginate and carboxybetaine methacrylate, and the like, and any other combination and collocation modes are not described in detail herein.

A combination of polyacrylamide and sodium alginate is preferred.

Preferably, the cross-linking agent comprises any one of calcium sulfate, N' -methylenebisacrylamide, 3-mercaptopropyltrimethoxysilane, propyl 3- (trimethoxysilyl) methacrylate, 1-carboxy-N, N-dimethyl-N- (3-acrylamidopropyl) ethylamine inner salt or 1-carboxy-N-methyl-N, N-bis (2-methacryloyloxy-ethyl) methylamine inner salt, or a combination of at least two thereof; such as the combination of N, N '-methylenebisacrylamide and 1-carboxy-N, N-dimethyl-N- (3-acrylamidopropyl) ethylamine inner salt, the combination of N, N' -methylenebisacrylamide and 1-carboxy-N-methyl-N, N-bis (2-methacryloyloxy-ethyl) methylamine inner salt, and the like, and any other combination and arrangement thereof will not be described herein. Calcium sulfate and 3- (trimethoxysilyl) propyl methacrylate are preferred.

Preferably, the initiator comprises any one or combination of at least two of ammonium persulfate, benzoyl peroxide, benzophenone, α -ketoglutaric acid or 2-hydroxy-4 '- (2-hydroxyethoxy) -2-methyl phenylpropanone, such as the combination of ammonium persulfate and benzoyl peroxide, the combination of benzophenone and α -ketoglutaric acid, the combination of benzoyl peroxide and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl phenylpropanone and the like, and any other combination collocation manner is not repeated here.

Preferably, the solvent comprises any one of water, glycerol, ethylene glycol, propylene glycol, butylene glycol, dipropylene glycol, diethylene glycol, tripropylene glycol or ethanol or a combination of at least two thereof; the combination of at least two of the above-mentioned components, such as the combination of water and glycerin, the combination of glycerin and ethylene glycol, the combination of propylene glycol and butylene glycol, etc., and any other combination and collocation manners are not repeated herein. Water is preferred.

Preferably, the raw materials for preparing the hydrogel further comprise an auxiliary agent and/or an auxiliary material.

Preferably, the auxiliary agent includes any one or a combination of at least two of a contrast agent, a stabilizer or a drug, where the combination of at least two of the contrast agent, the stabilizer or the drug, the contrast agent and the drug, and the like, and any other combination and collocation manner is not repeated here.

Preferably, the auxiliary material includes any one or a combination of at least two of the fiber, the microsphere, or the developing material, and the combination of at least two of the fiber and the microsphere, the microsphere and the developing material, the fiber and the developing material, and the like, and any other combination and collocation manner is not repeated herein.

Preferably, the hydrogel has a gel time of 0.1-30min, such as 0.1min, 0.5min, 1min, 5min, 10min, 15min, 20min, 25min or 30min, etc.

In another aspect, the present invention provides the use of a treatment system as described above in the manufacture of a device for the treatment of vascular pathologies.

In still another aspect, the present invention further provides a method for using the treatment system, which specifically comprises:

(1) the auxiliary forming unit (such as a bracket, a balloon and the like) is used for being placed in a blood vessel to restore normal blood flow or provide necessary assistance for hydrogel forming;

(2) selecting hydrogel with proper and different characteristics (such as injectable, degradable or self-adhesive hydrogel and the like) for different lesions, mixing the hydrogel by a mixer, conveying the hydrogel to a lesion site (a site to be filled) by a conveying unit, and initiating the hydrogel by necessary conditions (temperature, light, an initiator or mixing of different components);

(3) and after the hydrogel is gelled, removing the redundant auxiliary forming units, and reserving part of auxiliary forming units in special cases.

Compared with the prior art, the invention has the following beneficial effects:

the treatment system related by the invention has wide application, can be applied to the treatment of various types of vascular lesions and has high curative effect, and can be easily adapted to aneurysms, vascular malformations and varicose veins with different tumor cavity shapes. The treatment system adopts hydrogel with good biocompatibility to fill the abnormal part of the blood vessel, so that the abnormal part of the blood vessel can be well adhered with the vascular tissue, further expansion of aneurysm and reverse tearing of an interlayer can be prevented, and the artery with possible blood backflow can be blocked; the blood vessel can be completely filled, fixed and molded according to tumor bodies with different shapes, so that residual tumor cavities caused by other filling modes are avoided, and meanwhile, the blood vessel can be molded and the branch artery can be reconstructed according to the blood vessel shape; in addition, the treatment system can be filled with hydrogel with similar elastic modulus according to the specific conditions of the treatment part, so that the recurrence rate of the lesion part is reduced, and the foreign body sensation is reduced.

Drawings

FIG. 1 is a schematic view of a procedure for treating an abdominal aortic aneurysm using the treatment system of the present invention;

FIG. 2 is a schematic view of a procedure for treating an abdominal aortic aneurysm using the treatment system of the present invention;

FIG. 3 is a schematic illustration of a procedure for treatment of aortic dissection with the treatment system of the present invention;

FIG. 4 is a schematic illustration of a procedure for treating an aneurysm having a branch vessel with the treatment system of the present invention;

FIG. 5 is a schematic view of a procedure for treating an arteriovenous fistula utilizing the treatment system of the present invention;

fig. 6 is a schematic view of a procedure for treating varicose veins using the treatment system of the present invention.

Detailed Description

The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.