WO2007113833A2

WO2007113833A2 - Minimally invasive system for treating hollow organ dilatation

Info

Publication number: WO2007113833A2
Application number: PCT/IL2007/000446
Authority: WO
Inventors: Amos Cahan; Mickey Scheinowitz; Hanna Dodiuk-Kenig
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-04-04
Filing date: 2007-04-10
Publication date: 2007-10-11
Anticipated expiration: 2008-10-04
Also published as: WO2007113833A3

Abstract

The present invention discloses a kit for in vivo treating dilation of target organs. The kit comprises of a biocompatible and bioadsorbable polymerizable liquid; an applicator tool for applying said liquid polymer over said portion; and, curing means adapted to solidify said liquid polymer to a measure it provides a counter mechanical support to said organ. The invention further discloses a method for treating of dilation of organs. This method comprises steps of (a) applying of sufficient amount of at least one biocompatible and bioadsorbable polymerizable liquid over the exterior area of said dilated organ; and curing said liquid polymer in situ by means of radiation to a measure it solidifies and provides a counter mechanical support to said organ.

Description

MINIMALLY INVASIVE SYSTEM FOR TREATING HOLLOW ORGAN DILATATION

FIELD OF THE INVENTION

This invention generally relates to medical procedures and more specifically to a system for treatment of hollow body portion dilatation by a novel approach of placing an adhesive polymer support on the exterior of the dilated area. The invention may also be used as a preventative treatment system for preventative treatment of potential dilatation of a hallow organ.

BACKGROUND OF THE INVENTION

Dilatation of hollow organs is a common feature in several diseases thai involve severe risks, often times life threatening, to the patient. Such diseases include congestive heart failure (CHF), thoracic aortic aneurysm, abdominal aortic aneurysm, and colonic diverticulosis. Degradation of collagen which constructs the external matrix of the vessel is in most cases the factor that initiates the dilatation process. According to La Place's law, the tension on the wall of a vessel is proportional to the vessel's radius and inversely proportional to the wall thickness. Thus, dilatation of a vessel results in increased tension on its wall, along with diminution in its thickness and mechanical strength. The combination of these may form a vicious cycle leading to further dilatation. Dependent on the specific body portion involved, such as an artery, a ventricle of the heart or the colon; this may cause severe disease, and may demand surgery to prevent or to treat.

Currently there are several medical procedures that offer possible clinical treatment for dilatation of hollow organs. Despite their partial success, these treatments are highly risky, complicated, expensive, and require long rehabilitation.

CHF is the end point of several pathologies of the heart, including, among others, ischemic heart disease, valvular heart disease, inflammatory disease, infection and other causes that impair cardiac muscle contraction. Inadequate contraction is followed by compensatory ventricular dilatation, which, to some extent, may augment cardiac output according to the Frank-Sterling diagram. However, continued ventricular dilatation eventually reduces the muscle's ability to contract and decreases cardiac output.

Patients with CHF have impaired quality of life and increased morbidity and mortality. CHF patients that are unresponsive to medical therapy (diuretics, beta-adrenergic blockers, ACE inhibitors, spironolactone) are candidates for surgical intervention. Heart transplantation is the most effective of these, but the complexity and price of the procedure, as well as shortage in heart donors make it irrelevant for many patients. A left-ventricle assist device is implanted surgically and may serve as a bridge to transplantation.

Several techniques are available to improve function of the native failing heart. These techniques, based on La Place's rule, try to reverse the vicious cycle of cardiac dilatation and reduced left ventricular function by reducing cardiac diameter and decreasing the tension over the ventricular wall. The Acorn device uses a knitted polyester sock that is placed over the heart and surrounds it in order to limit left ventricular dilation. Cardiac reconstruction techniques such as the Dor and SAVER procedures aim at improving cardiac contraction by exclusion of akinetic or dyskinetic portions of the ventricular wall, such as a ventricular aneurysm or scar tissue. The Dor procedure is specifically indicated in case of a ventricular aneurysm. Developing in more than 10% of patients with Q wave myocardial infarction, this condition may reduce systolic function and be the source of life-threatening tachyarrhythmia, mural thrombus and embolization. A left ventricular pseudoaneurysm or false aneurysm is the result of contained cardiac rupture by adherent pericardium. This condition is most frequently a complication of myocardial infarction and, when untreated, carries an almost 50% mortality rate. Surgical treatment improves survival but carries a significant mortality risk.

Patients with CHF have greatly increased surgical risk and would benefit from a minimally invasive procedure to improve their heart function. Unfortunately, no such treatment is currently available.

The most frequent cause of death in patients with an untreated large thoracic aneurysm is complications arising from this condition, and estimated survival at five years is 20%. Aneurysm diameter is the best predictor of rupture. Aneurysm diameter grows over time at a variable rate of 0.1 to 1 cm per year. Surgical treatment is indicated for symptomatic aneurysms, rapidly expanding aneurysms, or aneurysms over 5-6 cm in diameter (these carry an annual risk of rupture, dissection or death of 15%). However, the variable natural history of the disease makes it difficult to decide when to operate, especially considering that many patients with aortic aneurysm are at increased surgical risk because of concomitant diseases.

An aneurysm of the ascending aorta is surgically accessed by median sternotomy, whereas descending aneurysms are approached using left thoracotomy. Most commonly, a Dacron graft is used for aneurysm repair, but a xenograft or a cadaver aorta may be used as well.

Surgical thoracic aneurysm repair is a dangerous procedure. Often, cardiopulmonary bypass with a cardioplegia-arrested heart and other measures are required to avoid end organ hypoperfusion, but complications, including paraparsis or paraplegia, are not uncommon.

Catheter-based intra-luminal stent grafting in thoracic aortic disease is a relatively new approach, the role of which in practice remains to be determined. Preliminary data show 9% early mortality risk and frequent complications.

An abdominal aortic aneurysm (AAA) is present if the aortic diameter is greater than 1.5 times the diameter measured at the level of the renal arteries (normal range 1.4-3 cm). About 1 percent of men aged 55-64 have a clinically important aneurysm and prevalence increases by 2-4% per decade thereafter. Aneurysms expand on average about 0.3 to 0.4 cm per year. Abdominal aortic aneurysm is more common in patients with atherosclerosis, when there is family history of AAA. Inflamation or infection may also cause AAA. Abdominal aortic aneurysms can cause embolization or thrombosis. Rupture of an AAA is usually lethal.

Elective resection is indicated for aneurysms 5.5 cm in diameter, for those dilating by more than 0.5 cm within 6 months, or for symptomatic aneurysms. Elective surgery carries a mortality risk of 2.5-6%, and concomitant disease or emergent setting increases this risk substantially.

Endovascular repair is an alternative to surgery. The prior art presents numerous variations of this procedure such as US 5,782,905 granted to Richter, US 5,951,599 to McCrory and US 6,309,367 to Boock to name a few. In this procedure, an artificial tube-shaped graft is inserted into the lumen of the aneurysm through femoral artery catheterization. Tube ends are attached to the aortic wall to allow blood flow only within the graft, minimizing risk of rupture. Each graft is individually tailored to fit a specific patient, based on imaging tests. Following graft insertion, a thrombus is formed around it, leading over time to shrinkage of the aortic sac in some cases. This may compromise graft function. A post-implantation syndrome characterized by fever, leukocytosis, elevation of inflammation markers may develop. Short-term mortality is reduced using endovascular repair, especially in patients with high surgical risk, but there appears to be no benefit using this approach in the long term. The price range of an endovascular device is $10,000 to $15,000, whereas a surgical graft costs less than $1,000. Moreover, overall hospital costs are not reduced using this approach.

Another alternative to surgery is presented in US 5,785,679 granted to Abolfathi et al. in which first a hollow balloon catheter is transluminal^ disposed within the aneurysm so that its proximal and distal ends extend past the aneurysm and then a synthetic molding material or a biological hardening agent is injecting into the aneurysm cavity which solidify it to create a new lining for the organ or vessel and the balloon catheter is deflated and removed thereafter. Although this approach solves the risks of keeping a foreign object such as a stent within the lumen, it still carries risks of injury especially in the process of the balloon inflation and it preserves a permanent contact between the hardened volume and the blood stream.

Another approach is disclosed in US 6,648,911 by Sirhan et al. which use a member that is placed over the exterior of the lumen and another supportive internal member that is placed internally, possibly as acombination with a grafted stent. This technique requires very delicate and timely workup since it involves manual coiling of the external member with applying a precise pressure on the lumen.

Diverticulosis of the colon is a common disorder affecting about a third of the population over the age of 60. Diverticula are formed by herniation of the mucosa and submucosa across the muscular wall of the colon. Diverticula are most common where the bowel wall where blood vessels penetrate. The formation of diverticula may compromise colon motility and cause constipation, which further aggrevate herniation. Complications of diverticular disease in the colon include diverticulitis (inflammation), fistula formation and rectal bleeding. Surgical resection of the affected colon is indicated in complicated diverticulitis, in recurrent episodes of diverticulitis and in case of fistula formation.

The invention disclosed herein utilizes bioabsorbable and biocompatible adhesives as a solution for dilatation of hollow organs. Soft tissue adhesion in vivo is well known in the art. In one of the first examples in the field is US 3,223,083, disclosing a non-toxic adhesive composition made of 2-methyl cyano acrylate and gelatin that can bind wet tissues such as fractured bones or torn tendons in vivo, and is depleted by new cells as the damaged tissue heals. US 3,527,841 presents means for controlling the viscosity by poly(lactic acid) that serves as a thickener to the alpha acrylate monomer, and for adding a radical scavenger.

Polyurethanes serve as good biocompatible polymers since the repetitive carbonate bond does not hydrolyze in vivo, hence lending stability to the polymer. They me be prepared as a copolymer comprising two components, a soft polyol and a hard diisocyanate. The soft component usually comprises an aliphatic chain that confers flexibility, whereas the rigid components such as contain rigid aryl components the more rigid urethane bond. Iscyanates containing an aliphatic chain are semi-rigid. The side chain functional groups also determine the characteristic of the outcome polymer, and the degree of cross-linking.

There are therefore many variables that enable the adjustment and tuning of the polymer to have the desired adhesiveness and elasticity which required for the specific application of the polymer.

One of the most stable bio-durable polymers is a polycarbonate urethane since the carbonate bond is stable toward hydrolysis and oxidation. US 6,177,522 discloses polycarbonate urethane polymers that are prepared by reacting polycarbonate polyols with an isocyanate and a chain extender that exhibit resistance to attack by in vivo agents over extended periods of time.

When using a polymer in vivo, its biocompatibility is also an important factor. Biocompatibility is defined as the degree of compatibility between the foreign element and the surrounding biological environment. A highly biocompatible implant will maintain its performance and functionality for a prolonged time. Some degree of interaction between the implant and its physiological environment improves its biocompatibility. This may be achieved by creating recognition of the foreign implant by the body by means of adsorption of proteins to its surface instead of rejection of the implant without having over adsorption that will lead to clogging of the implant by tissue formation on its surface. One method of finding the right balance is by making an implant with a semi-rough surface. Other important factors that influence the biocompatibility of the implant are the hydrophobic character, charge, polarity, surface energy, wettening abilities, chain mobility, functional groups distribution, and surface morphology. When applying a biocompatible adhesive on a soft tissue as a blood vessel it should have a number of characteristics: a Tg below room temperature which allows sufficient elasticity to bear any movement of the tissue during the adhesion; hydrophilic functional groups that allow a high degree of surface wettening and hydrogen bond formation with the tissue for stronger adhesion; ability to form hydrogen bonds with the tissue; an optimal molecular weight — high enough for formation of adhesion areas but low enough for adequate fluidity; and sufficient surface strain. Additionally the adhesive including the solvents and additives that might migrate from it, or any degradation by products are required to be non-toxic, and the exothermic reaction of the cross linking process should be minimal so not to over heat the tissue. It is also desirable that removal of the adhesive does not cause any damage to the soft tissue.

Usage of UV polymerization in the cross-linking step removes the need to use solvents in the process, and is a very fast process, usually in the order of few minutes, which are a significant advantage. The UV radiation induced polymerization requires a photoinitiator such as a benzoin a benzophenone, which initiates a radical polymerization of unsaturated components in the main polymer chains.

US 5,674,921 presents a radiation-curable prepolymer of a polyurethane endtipped with an hydroxy (acrylate or methacrylate) which can be crosslinked via UV irradiation, show bioabsorbability and biocompatibility with bodily tissue whilst maintaining the mechanical properties of a polyurethane.

Polymers are also used for coating the surface of medical implants for enhanced biocompatibility. Such a coating can further contain a chemically bounded therapeutic agent that is slowly released to the body. For example, Pinchuk in U.S. 5,092,877 describes a stent that is used for internal support of blood vessels, which has a drug releasing coating. US 6,099,562 introduces a modified coated stent in which the coating polymer containing the biologically active agent is partially covered by a topcoat polymer layer, allowing a timely release of the biologically active agent.

Thus, biocompatible and bioadsorbable adhesives provide an available technology to address the need for a cost effective, low risk, and simplified alternative approach for treating dilated hollow organs. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 discloses a flow chart of a method for treating of dilated hollow organs according to one embodiment of the invention; and,

Figure 2 illustrates an abdominal aortic aneurysm before (left) and during (right) application of a supporting polymer according to yet another embodiment of the invention.

SUMMARY OF THE INVENTION

According to one embodiment of the invention a kit for in vivo treating dilation of organs is disclosed. The kit comprises of (a) a biocompatible and bioadsorbable polymerizable liquid; (b) an applicator tool for applying said liquid polymer over said portion; and (c), curing means adapted to solidify said liquid polymer to a measure it provides a counter mechanical support to said organ. This biocompatibility is the ability of a liquid and solid polymer to perform an effective counter mechanical support to said organ in thus to treating dilation of the organ. This curing refers to the toughening or hardening of a polymer material by cross-linking of polymer chains. The term 'solidify said liquid polymer' refers to a polymer characterized by elasticity adapted to effective counter mechanical support. It is in the scope of the invention wherein the aforesaid polymer support is temporarily implanted, and it is at least partially removed after a defined measure of time. It is also in the scope of the invention wherein the polymer is at least partially disintegrated, absorbed or otherwise extracted from the treated organ after a defined measure of time.

Another embodiment of the invention is wherein at least a portion of this polymer is a liquid monomer.

Another embodiment of the invention is wherein at least a portion of this kit additionally comprises of an effective measure of photoinitiator.

Another embodiment of the invention is wherein this curing means is adapted to irradiate said polymer, especially UV radiation, and hence to solidify it.

Another embodiment of the invention is wherein this polymerizable liquid comprising monomers selected from a group consisting of epoxy acrylates, urethane acrylates, polyether acrylates, polyester acrylates, derivatives and mixtures thereof. Another embodiment of the invention is wherein this organ is hollow, and is selected from one or more members of a group consisting of arteries, veins, ventricles of the heart, bones, organs of the upper or lower gastro internal tracks, especially the colon. Another embodiment of the invention is wherein this hollow organ is the aorta.

Another embodiment of the invention is wherein this organ is a tumor.

Another embodiment of the invention is wherein the kit additionally comprises of at least one introducer adapted to introduce said liquid and said curing means to the targeted organ in a minimal invasive technique, especially laparoscopy and cervical mediastinoscopy techniques.

Another embodiment of the invention is wherein the kit additionally comprises of at least one introducer adapted to introduce said liquid and said curing means to the targeted organ in open surgeries.

Another embodiment of the invention is wherein the curing means is adapted to radiate the liquid with an effective measure of radiation being the UV and/or visible-light regions, especially in wavelengths between about 100 to about 380 nanometers. The term UV region is related to ultraviolet light being an electromagnetic radiation with a wavelength shorter than that of visible light, but longer than soft X-rays. The term related also to near UV (400-200 nm wavelength), far or vacuum UV (200-10 nm), and extreme or deep UV (1-31 nm). Visible-light, e.g., in the spectra of about 400 to 750 nm is also applicable. A laser device and fiber optics that can be brought close enough to the adhesive area are possible applicators for this UV and/or visible- light.

Another embodiment of the invention is wherein the curing means is adapted to radiate the said liquid with an effective measure of radiation being within the spectrum of visible light.

Another embodiment of the invention is wherein the curing means is adapted to emit an effective measure of heat so as to solidify the said liquid.

Another embodiment of the invention is wherein the curing means is adapted to deliver redox (reduction oxidation) agents in an effective measure to solidify the said liquid.

Another embodiment of the invention is wherein the curing means is adapted to radiate the said liquid with an effective measure of radiation being within the infra-red spectrum. The term effective measure refers here to a measure useful to solidify the liquid polymerizible matter such that a flexible polymer is obtained and this polymer is suitable to provide a counter support to the treated organ. The term also refers to an adequate intensity and duration for sufficient cross linking of the polymer for the purpose of providing mechanical support to said dilated hollow organ

Another embodiment of the invention is wherein the polymer comprises of at least one therapeutic active agent to be sustained released into the dilated hollow organ. This therapeutic active agent is selected, in a non-limiting manner, from drugs, pharmaceuticals, biocides, medicaments of biological or chemical nature. This therapeutic active agent is possibly adapted from either chronic or acute therapy.

Another embodiment of the invention is wherein the kit comprises of one or more polymerizable liquids, adapted to form a multilayered mechanical support to the organ. The multilayer comprises of at least one inner polymeric layer and at least one external polymeric layer.

Another embodiment of the invention is wherein the kit comprises of photo-initiator, selected from a group consisting of benzoin, benzophenone or any mixtures thereof.

Another embodiment of the invention is wherein the kit comprises of a cationic polymerization agent, radical polymerization agent or a combination thereof.

Another embodiment of the invention is an integrated device as defined in any of the above, wherein the applicator tool is adapted to provide the said curing means.

Another embodiment of the invention is a method for treating of dilation of organs. The method comprises of (α) applying of sufficient amount of at least one biocompatible and bioadsorbable polymerizable liquid over the exterior area of said dilated organ; and (b) curing the liquid polymer in situ by means of radiation to a measure it solidifies and provides a counter mechanical support to said organ.

Another embodiment of the invention is wherein step (a) is applying at least a portion of said polymer is a liquid monomer.

Another embodiment of the invention is wherein step (b) is curing by means of initiating said polymer, especially radiating UV and/or visible-light, and hence solidifying said liquid.

Another embodiment of the invention is wherein step (α) comprising a step or steps of applying polymerizing liquid comprising monomers selected from a group consisting of epoxy acrylates, urethane acrylates, polyether acrylates, polyester acrylates, silicone acrylate, derivatives, mixtures thereof, or any possible formulation that can be cured in-situ by means of light, especially of the UV visible-light spectra.

Another embodiment of the invention is the method as defined above, wherein hollow organs are selected from one or more members of a group consisting of arteries, veins, ventricles of the heart, bones, organs of the upper or lower gastro internal tracks, especially the colon.

Another embodiment of the invention is the method as defined above, especially adapted for treating aorta aneurysm.

Another embodiment of the invention is the method as defined above, especially adapted for treating tumors.

Another embodiment of the invention is the method as defined above, wherein step (a) is applying said liquid and curing means in minimal invasive techniques, especially laparoscopy and cervical mediastinoscopy techniques.

Another embodiment of the invention is the method as defined above, wherein step (a) additionally comprising applying said liquid by a mans of an introducer adjacent to said dilated organ to be treated.

Another embodiment of the invention is the method as defined above, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being the UV and/or visible-light regions, especially in wavelengths between about 100 to about 380 nanometers.

Another embodiment of the invention is the method as defined above, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being within the spectrum of visible light.

Another embodiment of the invention is the method as defined above, wherein step (b) is curing by a means of radiating the said liquid with effective measure of heat so as to solidify the said liquid. Another embodiment of the invention is the method as defined above, wherein step (b) is curing by a means of delivering redox (reduction oxidation) agents in an effective measure to solidify the said liquid.

Another embodiment of the invention is the method as defined above, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being within the infra-red spectrum. The effective measure is related with the intensity and duration required for sufficient cross linking of the polymer for the purpose of providing mechanical support to said dilated hollow organ

Another embodiment of the invention is the method as defined above, comprising step or steps of applying at least one therapeutic active agent, especially by sustained releasing it into the dilated organ.

Another embodiment of the invention is the method as defined above, wherein step (a) is applying one or more polymerizable liquids, adapted to form a multilayered mechanical support to said organ; wherein said multilayer comprises of at least one inner polymeric layer and at least one external polymeric layer.

Another embodiment of the invention is the method as defined above, wherein step (b) is curing by means of at least one photo-initiator selected from a group consisting of benzoin, benzophenone and mixtures thereof.

Another embodiment of the invention is the method as defined above, wherein solidifying is provided by a cationic polymerization, a radical polymerization or a combination thereof.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of said invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, will remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide means and methods for minimally invasive treatment adapted to prevent, to stop or to reverse hollow organ dilatation.

The object of the present invention is to provide a technique to prevent, to stop or to reverse hollow body portion dilatation by applying an adhesive polymer layer over the external tissue of the dilated organ.

Another objective of this invention is to disclose such a technique which is cost effective, eliminates the need for an individually tailored made device that requires a series of imaging scans.

Another objective of this invention is to treat complications arising from such dilatation by applying therapeutic agents directly to the affected area and its immediate surrounding.

It is yet another objective to simplify the medical procedure in treating hollow body dilatation by using minimally invasive techniques, thus shortening the recovery time of the patient and reducing risks to the patient involved in prior art techniques.

It is further an objective of the present invention that if a need to detach the polymer from the body portion it covers arises (e.g. in order to perform a surgical operation on that portion), the polymer may be easily detached using physical or chemical means.

The advantages of the present invention over the prior art are elimination of pre-manufacturing of tailor-made aortic grafts to fit a specific patient based on a series of imaging studies; usage of an inexpensive and readily available polymer; elimination of the need to perform a conventional surgery on patients with aortic aneurysm of with heart failure that are at great surgical risk, which is required in some prior art techniques, thus reducing morbidity and mortality. Moreover, enabling treating patients who are unable to undergo surgery due to their general medical condition; elimination of risks associated with the use of endovascular grafts. As the polymer in the present invention is applied to the external wall of an artery, it is not exposed to the blood stream. Therefore, complications such as infection and thrombosis which are associated with exposure of the blood to foreign bodies are eliminated using the technology described herein. Moreover, blood leakage around endovascular grafts, a common complication associated with their use, is not possible using the technique disclosed in this invention; and, the risk of neurological damage due to the occlusion of a spinal artery by a misplaced graft is eliminated, since the polymer adjusts to the anatomic structures and does not compress or occlude blood vessels. To conclude, the use of a locally applied, self forming polymer is a cheaper, safer and more flexible alternative for treating a wide range of pathologies that involve hollow organ dilatation.

It is in the scope of the invention wherein a strain gauge is incorporated within or adjacent the polymer to monitor the mechanical forces produced over the polymer, the organ or both. This strain signal is possibly transmitted outside the body and read by a remote detector.

The term "about" refers hereinafter to a value being ±25% of the defined measure.

The term "cross linking" refers hereinafter to covalent bond formation between separate polymer chains.

The term "curing" refers hereby to transition from the liquid phase to the solid phase. More particularly, transition of a polymer to the solid hose is done through cross-linking of the main polymer chains.

The term "minimally invasive surgical technique" refers hereinafter to a medical procedure that is performed inside the body and is carried out by entering the body through the skin or an anatomical opening through the smallest damage possible to these openings.

The term "photoinitiator" refers hereinafter to a molecule that interacts with an irradiated photon to yield a reactive product such as a radical through as intramolecular homolitic bond cleavage or by generating an excited species that further reacts with a hydrogen radical donor to yield a radical. The radical product is potent to initiate a radical polymerization process. The term is generally related to any compound that, under absorption of light, undergoes a photoreaction, producing reactive species that capable of initiating the polymerization of the polymerizable constituents within the coating, and especially to radiation curing; radical photoinitiators; cationic photoinitiators; or any combination thereof. Hence for example amd in a non-limiting manner, the photo initiator is selected from a group consisting of l-(4-Fluorphenyl)-2-methyl-2- morpholino-1-propanone; l,7-bis(9-acridinyl)heptane; l-Chloro-4-propoxy thioxanthone; 1- Hydroxy cyclohexyl phenyl ketone; 2,2-Di ethoxy acetophenone; 2,3,4,4-Tetrahydroxy Benzophenone; 2,3,4-Trihydroxybenzophenone; 2,4,6-Trimethyl benzoyl diphenyl phosphine oxide; 2,4,6-Trimethylbenzophenone; 2/4-Diethylthioxanthone; 2/4-Isopropylthio xanthone; 2- Benzyl-2-(dimethylamino)-l-[4-(4-morpholinyl)phenyl]-l-butanone; 2-Chlorothio xanthone; 2- Dimethyl-aminoethylbenzoate; 2-Ethylhexyl-4-dimethylaminobenzoate; 2-Hydroxy-2-methyl- phenyl-propan-1 -one; 2-Hydroxy-4'-hydroxyethoxy-2-methylpropiophenone; 2-

Isopropylthioxanthone; 2-Methyl Benzophenone; 2-Methyl-l-[4-(methylthio)phenyl]-2- morpholinopropanone-1; 4-(4-Methylphenylthiophenyl)-phenylmethanone; 4,4'-Difluro benzo - phenone; 4,4'-Dimethoxy benzophenone; 4-Chloro benzophenone; 4-Hydroxy methyl benzphenone; 4-Methyl acetophenone; 4-Methyl benzophenone; 4-Phenylbenzophenone; Benzil dimethyl ketal ; Benzophenone; Benzophenone hydrazone; Bis (p-tolyl) iodonium hexafluoro- phosphate; Blend of 2-Isopropylthioxanthone and 4-Isopropylthioxanthone; Blend of Benzophenone and 4-Methylbenzophenone and 2-Methylbenzophenone; Dimethyl Sebacate; Diphenyl Iodonium Hexafluorophosphate; Ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate; Ethyl-4- (dimethylamino) benzoate; Methyl o-benzoyl benzoate; Methyl phenyl glyoxylate; N,N,N^?,N'- Tetraethyl-4,4-diaminobenzophenone; Phenyltribromomethylsulphone or any mixture thereof.

Reference is now made to figures 1 and 2. In a preferred embodiment of this invention a dilated hollow organ such as an abdominal aortic aneurysm (10) by the use of a liquid polymer mixed with a photoinitiator (20), which is applied in vivo over the desired area using a designated applicator tool (30). The tool is brought to the target body portion either by catheterization of an artery, a vein or a lymphatic duct, or by endoscopy or by minimally invasive surgical techniques such as laparoscopy or mediastinoscopy. Following its application, the polymer adopts a final three-dimensional structure, which is compatible to the exterior of the dilated hollow organ.

The three dimensional conformation of the polymer is stabilized by cross linking of the polymer which is preferably performed by UV irradiation to provide mechanical support to the wall of that body portion. The UV irradiation prompts radical formation by the photoinitiator, which in turn initiates the cross linking of the polymer through radical polymerization. The preferred cross linking is done through radical polymerization of unsaturated functional groups that are either placed as side chains or incorporated in the backbone of the polymer. The UV emitter tool can be catheterized as one combined tool with the polymer applicator in a preferred embodiment of this invention or consequentially as a separate tool in a second embodiment. The UV irradiation is conducted over short period time which is nonetheless sufficient for full curing of the polymer. The UV source is preferably a medium pressure mercury electrode (MDME).

In a second embodiment of this invention the substrate that is applied over the treated hollow body portion is a mixture of a monomer and a photoinitiator, and the polymerization takes place thereafter, preferably by UV irradiation induced radical polymerization.

In a non-limiting manner, the preferred polymer for this purpose is selected from a list of polymers including epoxy acrylates, polyurethane acrylates, polyether acrylates, polyester acrylates and derivatives and mixtures thereof.

In a non-limiting manner, the preferred photoinitiator is a radical producing substance such as benzoin or its derivatives, azo-bis-isobutyronitrile or its derivatives, benzophenone or its derivatives derivative, that generates a radical upon UV irradiation. The photoinitiators are preferably admixed into the liquid polymer preferably at 0.05% to 5.0% by weight most preferably 1.0% to 2.0% by weight

Polymer characteristics such as mechanical strength, thickness, plasticity and elasticity may be adjusted to optimally meet specific needs in specific body portions by varying the ratio between the soft component and its rigid component, the side chain groups and the density of crosslinking groups and their types.

The polymer may also contain chemicals for immediate or sustained release for therapeutic uses such as recruitment of fibroblasts and connective tissue formation over the polymer, preventing infection or clot formation or induction of angiogenesis to improve blood supply to that body portion.

When a need to detach the polymer from the body portion it covers arises (e.g. in order to perform a surgical operation on that portion), the polymer may be easily detached using physical or chemical means.

The liquid polymer that is used in this invention has the formula: A-B-C-D-E; wherein C is an oligomer or a polymer selected from groups I₅ II, III in which group I has the formula - 0(O)C(R¹ )yC(0)0(R²)_x- wherein x and y are the equal or different integers between 1 and 18 preferably 4 and R¹ and R² are equal or different straight or branched alkylene, oxaalkylene, halogenated alkylene, halogenatedoxaalkyl, or straight or branched alkenylene, oxaalkenylene, halogenated alkenylene, halogenatedoxaalkenylene or straight or branched alkynylene, oxaalkynylene, halogenated alkynylene, halogenatedoxaalkynylene, group II has the formula RO wherein R is a straight or branched alkyl, alkenyl, alkynyl or halogenated thereof

B and D are equal or different and are selected from groups IV, V, VI wherein group IV O(O)CNH(C₆H₅R⁵)NHC(O)O wherein R⁵ is hydrogen or a C₁-C₄ alkyl, alkenyl or alkynyl group and R⁴ is a straight or branched alkylene, oxaalkylene, halogenated alkylene, halogenatedoxaalkyl, or straight or branched alkenylene, oxaalkenylene, halogenated alkenylene, halogenatedoxaalkenylene or straight or branched alkynylene, oxaalkynylene, halogenated alkynylene, halogenatedoxaalkynylene.

A and E are equal or different and selected from groups VII, VIII, wherein group VII has the formula CH₂=CR³C(O)R⁴ wherein R³ is hydrogen or a CpC₄ alkyl, alkenyl or alkynyl group and R⁴ is a straight or branched alkylene, oxaalkylene, halogenated alkylene, halogenatedoxaalkyl, or straight or branched alkenylene, oxaalkenylene, halogenated alkenylene, halogenatedoxaalkenylene or straight or branched alkynylene, oxaalkynylene, halogenated alkynylene, halogenated-oxaalkynylene; group VIII has the formula CF₂CF(C₆H₆)

The general use of the system described in this invention is as follows: the applicator is charged with e.g., about 0.1 or less to about 250 or more grams of the polymerizable liquid. When the applicator is placed above the treatment area, a mechanism in the applicator is activated and the liquid polymer is released from the applicator device in at an adjustable rate as determined by the user through the mechanism. By activating the designated curing device the liquid polymer is then irradiated e.g., by UV irradiation preferably in the range of about 315 or less nm to about 400 or more nm and most preferably at e.g., about 370 nm in an intensity of e.g., 700 mWatts. The designated curing device is most preferably equipped with a medium pressure mercury electrode which irradiates at wavelengths between about 200 or less nm to about 440 or more nm. While the invention will be hereinafter described by a number of Examples, it should be clearly understood that these examples are presented only for a better understanding of the invention, without limiting its scope. A person skilled in the art after reading the present specification will be in a position to insert some modifications without being outside the boundaries of the invention as covered by the appended Claims.

In all the examples given hereby the adhesive tensile strength tests were performed using an Instron 6993 TM instrument.

Example 1

A human abdominal aortic aneurysm is covered by about 1 to about 3 mm thick layer made of a mixture containing polyurethane acrylate and 0.5% w/w benzoin, which is applied by the designated applicator.

The thin layer is thereafter irradiated for 5 sec/cm2 by the designated curing UV radiating device, especially a fiber optic that was brought close enough to mixture, at range from 200 nm to 440 nm and 700 mWatts, yielding a cured cross linked polymer which is characterized by an effective adhesive tensile strength, e.g., strength allowing no more than about 5% radial expansion of this hollow organ.

Example 2

Same as example 1 except that a dilated portion of a colon was treated instead of a blood vessel to yield a polymer which is characterized by an effective adhesive tensile strength.

Example 3

Same as example 1 except that a human abdominal aortic aneurysm is covered by 1 to about 3 mm thick layer made of a mixture containing polyurethane acrylate and 2-hydroxy-2- phenylacetophenone (benzoin) 0.5% (w/w), which is applied by the designated applicator. The thin layer is thereafter irradiated for 5 sec/cm² by the designated curing UV radiating device, especially a laser, at 200 nm to 440 nm and 700 mWatts, yielding a cured cross linked polymer which is characterized by an effective adhesive tensile strength.

Example 4

Dacron sheets are soaked with liquid polyurethane acrylate and then are attached to a 2 cm in diameter glass rod thereafter they are irradiated at the same wavelength and intensity as in example 1 to yield a polymer which is characterized by an effective adhesive tensile strength.

Example 5

Same procedure as example 1 wherein a trifluorovynil cross linking group is used and no photoiniator is admixed to the liquid polymer yielding a polymer which is characterized by an effective adhesive tensile strength.

Claims

1. A kit for in vivo treating dilation of target organs, comprising: a. a biocompatible and bioadsorbable polymerizable liquid; b. an applicator tool for applying said liquid polymer over said portion; and, c. curing means adapted to solidify said liquid polymer to a measure it provides a counter mechanical support to said organ.

2. The kit according to claim 1, wherein at least a portion of said polymer is a liquid monomer.

3. The kit according to claim 1, additionally comprising an effective measure of photoinitiator.

4. The kit according to claim 3, wherein said curing means is adapted to irradiate said polymer, possibly by a laser means or fibers optics, especially UV and/or visible-light radiation, and hence to solidify it.

5. The kit according to claim 1 , wherein said polymerizable liquid comprising monomers selected from a group consisting of epoxy acrylates, urethane acrylates, polyether acrylates, polyester acrylates, silicone acrylate, derivatives, mixtures thereof or any possible formulation that can be cured in-situ by means of light.

6. The kit according to claim 1 , wherein said target organs are selected from (i) hollow organs from one or more members of a group consisting of arteries, veins, ventricles of the heart, bones, organs of the upper or lower gastro internal tracks, especially the colon; or (ii) mumors..

7. The kit according to claim 6, especially adapted to treat dilation is aorta aneurysm.

8. The kit according to claim 1, additionally comprising an introducer adapted to introduce said liquid and said curing means to the targeted organ in a minimal invasive technique, especially laparoscopy and cervical mediastinoscopy techniques.

9. The kit according to claim 1, additionally comprising an introducer adapted to introduce said liquid and said curing means to the targeted organ in open surgeries.

10. The kit according to claim 1, wherein said curing means adapted to radiate the said liquid with an effective measure of radiation being the UV and/or visible-light region, especially in wavelengths between about 100 to about 380 nanometers.

11. The kit according to claim 1, wherein said curing means adapted to radiate the said liquid with an effective measure of radiation being within the spectrum of visible light.

12. The kit according to claim 1, wherein said curing means adapted to emit an effective measure of heat so as to solidify the said liquid.

13. The kit according to claim 1, wherein said curing means adapted to deliver redox (reduction oxidation) agents in an effective measure to solidify the said liquid.

14. The kit according to claim 1, wherein said curing means adapted to radiate the said liquid with an effective measure of radiation being within the infra-red spectrum.

15. The kit according to claim 1, wherein said polymer comprising at least one therapeutic active agent to be sustained released into the dilated hollow organ.

16. The kit according to claim 1 , comprising one or more polymerizable liquids, adapted to form a multilayered mechanical support to said organ; wherein said multilayer comprises of at least one inner polymeric layer and at least one external polymeric layer.

17. The kit according to claim 1, wherein said photo-initiator is selected from a group consisting of benzoin, benzophenone or any mixtures thereof.

18. The kit according to claim 1, wherein said polymerization is a cationic polymerization

19. The kit according to claim 1, wherein said polymerization is a radical polymerization.

20. The kit according to claim 1 , comprising a biocompatible and bioadsorbable polymerizable matter, selected from a gel, rubber-like composition, flowing matter, or any other shapeable pre-shaped matter.

21. An integrated device according to claim 1, wherein said applicator tool is adapted to provide the said curing means.

22. A method for treating of dilation of organs, comprising a. applying of sufficient amount of at least one biocompatible and bioadsorbable polymerizable liquid over the exterior area of said dilated organ; b. curing said liquid polymer in situ by means of radiation to a measure it solidifies and provides a counter mechanical support to said organ.

23. The method according to claim 22, wherein step (α) is applying at least a portion of said polymer is a liquid monomer.

24. The method according to claim 23, provided by one of the following three procedures: (i) directly, especially by open heart surgery; (ii) by minimal invasive means, especially thoracotomy; or (iii) endoscopically, especially by fiber optics means.

25. The method according to claim 22, wherein step (b) is curing by means of irratiating said polymer, possibly by using either laser or fiber optics, especially radiating UV and/or visible-light, and hence solidifying said liquid.

26. The method according to claim 22, wherein step (α) comprising a step or steps of applying polymerizing liquid comprising monomers selected from a group consisting of epoxy acrylates, urethane acrylates, polyether acrylates, polyester acrylates, derivatives and mixtures thereof.

27. The method according to claim 22, wherein said hollow organs are selected from one or more members of a group consisting of arteries, veins, ventricles of the heart, bones, organs of the upper or lower gastro internal tracks, especially the colon.

28. The method according to claim 27, adapted to treating aorta aneurysm.

29. The method according to claim 22, wherein said organs are tumors.

30. The method according to claim 21, wherein step (a) is applying said liquid and curing means in minimal invasive techniques, especially laparoscopy and cervical mediastinoscopy techniques.

31. The method according to claim 22, wherein step (α) additionally comprising applying said liquid by a mans of an introducer adjacent to said dilated organ to be treated.

32. The method according to claim 22, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being the UV and/or visible-light region, especially in wavelengths between about 100 to about 380 nanometers.

33. The method according to claim 22, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being within the spectrum of visible light.

34. The method according to claim 22, wherein step (b) is curing by a means of radiating the said liquid with effective measure of heat so as to solidify the said liquid.

35. The method according to claim 22, wherein step (b) is curing by a means of delivering redox (reduction oxidation) agents in an effective measure to solidify the said liquid.

36. The method according to claim 22, wherein step (b) is curing by a means of radiating the said liquid with an effective measure of radiation being within the infra-red spectrum.

37. The method according to claim 22, additionally comprising applying at least one therapeutic active agent, especially by sustained releasing it into the dilated organ.

38. The method according to claim 22, wherein step (α) is applying one or more polymerizable liquids, adapted to form a multilayered mechanical support to said organ; wherein said multilayer comprises of at least one inner polymeric layer and at least one external polymeric layer.

39. The method according to claim 22, wherein step (b) is curing by means of at least one photo-initiator selected from a group consisting of benzoin, benzophenone and mixtures thereof.

40. The method according to claim 22, wherein solidifying is provided by a cationic polymerization

41. The method according to claim 22, wherein solidifying is provided by a radical polymerization.