Patent Publication Number: US-2019192836-A1

Title: Device and method for the lavage-type introduction of a fecal transplant or of a therapeutically effective substance into the colon of a patient

Description:
REFERENCE TO PENDING PRIOR PATENT APPLICATIONS 
     This patent application: 
     (i) is a continuation-in-part of International (PCT) Patent Application No. PCT/IB2017/001458, filed 27 Nov. 2017 by Advanced Medical Balloons GmbH for DEVICE FOR THE REPETITIVE SUPPLY AND DRAINING OF SUBSTANCES FOR MEDICAL THERAPY, AND SYSTEM AND METHOD FOR PRODUCING FECAL CONTINENCE BY INTERMITTENT COLON LAVAGE BY MEANS OF A PERMANENTLY PLACED TRANS-ANAL OCCLUDING OR ACCESS CATHETER, which claims benefit of German Patent Application No. DE 10 2016 014 053.4, filed 25 Nov. 2016; and 
     (ii) claims benefit of German Patent Application No. DE 10 2017 010 234.1, filed 4 Nov. 2017. 
     The three (3) above-identified patent applications are hereby incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     Medically indicated transfers of stool from a donor to a receiving patient are perfomed with increasing frequency. Especially in the treatment of chronical inflammatory deseases of the colon, good therapeutic results are achieved with so-called stool transplantations. 
     BACKGROUND OF THE INVENTION 
     For a most efficient transfer of the stool, the colon of the patient is normally defecated prior to the transplantation procedure, and is purged from the residual rests of stool. Subsequently, the stool to be transplanted is introduced either anterograde, from the oral side, endoscopically into the upper part of the small intestine, or retrograde, from the anus, via an ano-rectal enema into the colon of the patient. In both cases, the stool transplant is in a suspended state, normally in a highly fluid state. 
     Besides the efficiency of the preparative removal of the patient&#39;s microbiome, the success of the transfer depends particularly on the size of the achieved contact surface between the introduced stool and the receiving colon, as well as on the duration of the exposure with the stool transplant. 
     Nowadays, conventional enema systems generally used for the retrograde, ano-rectal transfer of stool comprise a shaft, which is to be introduced into the anus and which is provided with a retention balloon positioned in the rectal ampulla. The stream efficient diameter of such systems is small and does not allow neither an efficient rinsing (lavage) of the colon, nor an efficient large-area wetting of the colon surface with the stool suspension. The shaft bodies of conventional enema systems are normally made of relatively rigid materials, which do not exclude an accidential perforation of the colon wall by the shaft. For this reason, the recommended trans-anal utilisation period of a conventional enema system is limited to a few minutes. Principally, the application generally requires a continuous control by the applicant. Furthermore, commercially available enema systems are incapable of sealing against intestinal contents trickeling or leaking out of the anus during the procedure. Certainly, by a contraction of the sphincter, the patient can transiently suppress the running out of intestinal contents, but after a few minutes of contraction the sphincter muscle gets tired and the intestinal contents or the rinsing solution leak out passing around the catheter shaft. 
     Many patients usually perceive the firmly widened elastic retention balloon in the rectum as a foreign object. Some patients respond to the stimulus, which is initiated by the firm retention balloon in the rectum, with a reflective contraction of the rectum and with an opening of the anus. 
     SUMMARY OF THE INVENTION 
     The present invention overcomes these disadvantages by optimizing of the sealing performance in the anus, by minimizing the irritations typically resulting from a foreign body, by facilitating the entry of the substances to be instilled in the colon into the upper portions of the colon, by rendering the contact time between the substances deposited in the colon and the intestinal surface extendable to an arbitrarily long period of time, as well as by allowing the entry of thick, viscous transplants or substances into the colon. Together with the described deviece, the receiving or, respectively, treated patient may, in case of need, change from the lying position into a sitting position or even a standing position, without any anal leakage. 
     A further, decisive advantage of the invention is the option according to the present invention of a preceding, cleaning lavation and preparation of the colon, which is subsequently followed by the instillation of the transplant or of the respective agent. Thereby, the patient-sided portion of the device, especially the trans-anally placed head unit, may remain in the rectum, while the vessel, which is terminally connected to the patient-sided catheter, can be exchanged through a respective connecting function, dependending on the phase of the procedure, that is either lavage or instillation. 
     The device described in the following and the method enabled by the device, for a combined flushing-type cleaning lavage and a flushing-type therapeutical instillation especially facilitates repeated cycles of inflow into the colon and outflow from the colon, whereby in the inflow phase, the bag with the applied medium (rinsing solution for cleaning, stool transplant, pharmacological agent) is raised above the patient, and in the outflow phase, the bag is lowered below the level of the patient, so in summary a so-called “pivoting” enema is executed. 
     In case of the initial pivoting lavage with a cleaning liquid, the cycle of raising and lowering is repeated until the intestinal contents drained from the colon are free from shaped rests of the stool. If required, the bag which is used for the lavage, can be exchanged several times and filled with fresh cleaning liquid. The lavage bag, which was used for cleaning the colon, may subsequently be rotated by 180° and be fixed upside down at the lower bed frame, now having a collecting function and receiving, during an arbitrary period of time, the outgoing stool mobilized by the lavage, without contamination of the patient and the surroundings. 
     During the subsequent introducing of the transplant or of the active agent, the passing into the colon and out of the colon proceeds in a similar way through the repetitive “pivoting”. Thereto, the transplant or the active agent is inserted into an instillation bag similar to the lavage bag, and said bag is then connected the patient-sided portion of the device, which remains in the rectum of the patient during the whole procedure. Through the multiple cycles of flushing-type washing of a large volume of liquid into the colon and outflow of the bag&#39;s content from the colon, it is ensured that the mucous membrane of the upper portions of the colon, especially of the transverse colon and of the rightside ascending colon, too, is reached or, respectively, wetted by the transplant or by the agent. 
     Due to the particular trans-anal sealing mechanics of the device, which follows the anal sphincter muscle dynamically, the patient can retain the transplant or the substance inside the colon arbitrarily long and in almost every body position, with relaxed sphincter muscle, without the risk of a leakage of the intestinal contents out of the anus. Thus, for the respective application, an optimum exposure time of the medium instilled in the colon can be achieved. 
     After the end of the phase of the “pivoting” instillation, the respective bag may again be turned upside down and placed below the patient. Thereby, it is given a draining and collecting function, whereby the rest of the implant or of the agent contained in the colon can drain during an arbitrary period of time into the bag. During this phase, the patient may again adopt a comfortably relaxing posture. 
     With the device described in the context of the invention, also locally or topically active substances may be introduced into the large intestine, especially into its upper portions close to the small intestine. Such an option is of particular importance in the case of chronically inflammatory processes in the area of the junction between ileum and cecum. The introduced topically active substances may, for example, be of antibiotic nature or of non-antibiotic, anti-inflammatory nature, too. 
     The operating principle of the device is substantially based on a particularly flow-efficient large-lumen in- and outflow of the medium, whereby the inflow and outflow volume stream to and from the patient is adjusted in such a way that, during “pivoting”, a volume of 1000 mL is introduced in less than 30 seconds, preferably in less than 15 seconds, and, preferably, may also be drained. At such flow values, the substance which is to be introduced for the lavage or for the instillation, is washed as a flush into the colon. Furthermore, the device comprises a throttling function which limits the inflow. In case of an overlarge volume flow to the patient, irritating right up to painful sensations of the colon are possible. 
     In the context of the invention, for achieving a lavage-type introduction of a cleaning or an instillating liquid, volumes from 1000 to 2000 mL, preferably from 1200 to 1500 mL, are used and are filled into the respective vessels or bags in such an amount. 
     The inner diameters of all segments of the device are designed in such a way that the flow volumes as described above can be achieved. They are measured from 12 to 22 mm, preferably from 15 to 20 mm. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The structural and functional features of the device according to the invention are depicted in the following figures. 
         FIG. 1  shows a device for the lavage-type repetitive pivoting introduction of a cleaning liquid into the colon, said device comprising the patient&#39;s sided portion as well as the bag&#39;s sided portion, in a schematic overview. 
         FIG. 2  shows an embodiment of a combined lavage and collection bag for an optional lavage-type cleaning of the colon preceding the instillation of the substance. 
         FIG. 3  depicts a special flow limiting or, respectively, throttling function inside of the in- and outflow tube system, on the basis of the torsion of a tube. 
         FIG. 3 a    depicts a preferred arrangement of the throttling function at the proximal end of the patient&#39;s sided catheter unit. 
         FIG. 4  shows a preferred embodiment of a head unit with a shortened balloon body, remaining inside the patient during the procedure. 
         FIG. 5  shows a head unit with a mushroom-shaped distal insertion element. 
         FIG. 6  shows a further vessel implemented as a bag, which is optimized for the large-volume lavage-type instillation of a therapeutical substance into the patient&#39;s colon. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       FIG. 1  shows a device according to the invention, for the lavage-type “washing in” of a substance into the colon of a patient, comprising an anorectal placed head portion  2  remaining in the patient&#39;s anus over the whole duration of the procedure and comprising a dumbbell-shaped or a mushroom-shaped balloon element  3 , which combines the functions of a rectal retension and a trans-anal sealing and is mounted on a shaft element  4  which becomes elastically radially deformed or, respectively, folded when a force is applied on the wall of the shaft, and when the force in the anal channel is decreasing, spontaneously said shaft element  4  straightens up elastically. Upon an axial deflexion of the shaft&#39;s tube, said shaft element transforms from its trans-anal rest position into a single or multiple axial buckling, whereby any likelihood of potential perforations of the colon wall due to a shifting of the head portion of the drainage device into the upper intestines is almost excluded. Herein, the shaft element optionally has a corrugated, wavy profile, whereby, upon use of elastic materials such as for example polyurethane, good self-erecting properties can be achieved even at relatively small wall thicknesses of the shaft element on the one hand, and on the other hand, after overcoming of a special initial force for the transition of the shaft into the folded or compressed state, the radial folding and the axial compression of the shaft wall can proceed with a lower necessary force in the course of the further deformation of the shaft profile, or, respectively, the radial and axial deformation is relieved in comparison to the initial deformation. 
     A tube part  5  adjoins to the shaft tube proximally, which transitions at the free end into a catheter-sided connector element  6 . The connector enables a reversibly detachable connection to a preferably bag-shaped vessel  7 , which can be filled through a closable opening  8 . The vessel  7  comprises a tube element  10 , which changes over into a connector element  11 , which is compatible with the connector  6 . In the transition area to the tube  10 , the vessel  7  integrates a flow restricting function  9 , which either presets the outflow from the vessel fixedly through the number and size of openings, or is variably adjustable. Additionally to a bag-sided integrated throttling or, respectively, closing element, a separately implemented, simple, clamp-type or slidable closing element  12  can be inserted into the tube element optionally, preferably close to the connector. 
       FIG. 2  shows a vessel  7  according to the invention, which is implemented as a foil bag and primarily performs the function of a lavage-type cleaning colon rinsing, which preceds the “washing in” of the substance to be instilled in the application procedure. The bag comprises a handle  13  at the upper end. Preferably, the bag comprises only a single chamber, in which, during the pivoting procedure, the fresh flushing medium mixes with the content drained from the colon. The chamber is filled through an opening  8  at the upper end of the bag and is closed in a leakproof manner. At the bottom, the bag comprises an outlet portion  14 , where a tube connector  10   a  is welded. Outwardly, the combined inlet and outlet tube  10  adjoins to said tube connector. Inwardly, said tube connector lines up with a thin-walled tube portion  10   b , which has a valve-like function within the bag. The portion of said tube connector  10   a , which protrudes inside the bag, is perforated. On the one hand, this special type of construction of said tube connector allows to separate formed stool, which is already in the bag, and to feed back only fluid content of the bag to the patient for the further irrigation. On the other hand, the volume stream can be throttled or, respectively, restricted through the perforations  15  of said tube connector in a fixed, that means not adjustable manner. The tube  10  outgoing from said tube connector should have a length from approx. 1.0 to 1.7 m, preferably from 1.3 to 1.5 m. 
     By means of the handle  13 , the bag can be pivoted comfortably during the cleaning procedure. After the completion of the raising and lowering cycles, the bag is turned upside down and fastened at a level below the patient in a thenceforth collecting function. On its bottom edge, the bag comprises respective openings  16  for an upside down hanging position. Furthermore, it comprises a scale  17   a  for the detection of the inlet volume used for the cleaning (in-scale) and an out-scale  17   b  for the detection of the volume entirely received from the colon of the patient. Therefore, a balance can be made for the cleaning procedure, and the rest volume remaining inside the colon can be determined. 
       FIG. 3  shows a possible embodiment of the functional element  19 , which combines the throttling, that means flow restricting function and the closing function. The mechanism comprises two sleeves  19   a  and  19   b  coaxially to each other, which can rotate against each other around their common axis or, respectively, be twistable relative to each other to a certain angle value, whereby a foil tube element  20   a  is arranged inside the sleeves  19   a ,  19   b  preferably coaxially to the common axis of the both sleeves  19   a ,  19   b  in such a way that one of its ends is connected to the inner wall of one sleeve part  19   a  and the other of the both ends is connected to the inner wall of the other sleeve part  19   b , which is positioned in an axial alignment. If the sleeves  19   a ,  19   b  are twisted relatively to each other around their common axis, for example for an amount from 90° to 270°, or even beyond that, said tube element  20  gradually transitions from its axial aligned, open lumen rest position into a twisted position with closed lumen, whereby the free lumen L of the tube increasingly narrows with increased rotation and finally closes completely. The functional element  19  can be integrated both in the catheter-sided tube segment of the device and also in the bag-sided tube segment, whereby it is preferably arranged as close as possible to the connector. 
     As an example,  FIG. 3 a    shows the positioning of the flow controlling functional element  19  in the terminal connector  6  at the tube  5  of the head unit  2 . Here, the element  19  serves for sealing the tube during the phase of exchanging the bags, so that the fluid remaining in the intestinals can be kept safe inside the colon, and a leakage through the temporarily opened connector into the surroundings can be avoided. A transparent sleeve element  23  can adjoin immediately distally to the throttle, that means towards the patient, which renders the in- and outflowing fluid or, respectively, its particular quality and the actual volume flow visible. Optionally, a sleeve element or both sleeve elements  19   a ,  19   b  can be made out of transparent material. 
       FIG. 4  shows an exemplary head unit  2  in detail, whereby it comprises a balloon component  3 , which is not dumbbell-shaped, but in a shortened form mushroom-shaped. The proximal portion  3   b  of the balloon body extends through the anal channel, the distal portion  3   a  is placed inside the rectum. The trans-anal portion  3   b  can optionally terminate in line with the outer opening of the anus, the anal ring, or may also extend beyond the plane of the anus as a connector. As a less preferred embodiment, lengths of the portion  3   b  can be chosen, which would only reach into the anal channel, but do not extend up to its outer opening. The shaft element  4  comprises an olive-shaped or a ring-type extension  21 , which facilitates the insertion into the anus. Preferably, the shaft element is made of polyurethane and comprises within its area supporting the balloon a wavy profile  22  aiding the elastic self-erection of the shaft. 
       FIG. 5  shows a further embodiment of the head unit  2 , whereby this comprises shaft element  4   a  supporting the balloon body  3 , which has a special mushroom-shaped, conical/tapered tip  4   b . Contrary to the aforementioned embodiments like e.g. in  FIG. 4 , the balloon body is shortened in its distal intra-rectal portion  3   a , but alltogether yet of a dumbbell shape. Its middle portion  3   c  is tapered and provides, upon a respective positioning of the balloon tapering, a dynamically adaptive, trans-anally effective seal performance adjusting to the respective rectal pressure, as described in context with the invention. The whole shaft body, that is the tip  4   b , the proximally adjoining shaft portion  4   b  as well as the pre-anal adjoining portion  4   c , can be cast or injection molded from a soft, foam-like or jelly-like material. 
     The implementations depicted in  FIGS. 4 and 5  of the balloon body comprising an intra-rectal balloon segment with a large diameter and a trans-anal segment extending through the anus or even only into the anus, enable a special sealing dynamics, whereby the respective rectal effecting force is absorbed by the segment  3   a , and provides a continuous sealing in the anal channel in the segment  3   b  in a temporarily synchronous and corresponding manner. All segments of the balloon body are preformed during their manufacturing to their entire working dimensions or alternatively even beyond, that is residually dimensioned. Preferably, the fully shaped balloon is in situ filled incompletely, that is slackly, so the perception of the device as a foreign body is largely avoided. In its slacky filled shape, the balloon adapts in an optimum manner to the respective anal-rectal anatomy an to the respective prevailing rectal force. 
       FIG. 6  shows a bag-type vessel, which is optimized for the lavage-type washing in or, respectively, instillation of a substance into the colon of a patient. A sleeve-like handpiece  24  designed for gripping with a hand adjoins to the connector  11 , wherein a clamping-type or tongs-like closing element  25  is embedded, which in case of single-handed operation is opened by the thumb of the operator, and in its open state releases the entire lumen of the clamped tube section. For example, the element builds up a curved tension in its closed state, which relaxes through releasing of a latch  25   a  and leads to a rapid opening of the closure  25 . Again, a transparent element  23  can adjoin to the handpiece. The portion of the tube, which is installed in the lower end of the bag, comprises two or several lateral openings  26  of large lumen, so that the bag content is received in a most efficient way from the bag and a potential shift of a single terminal lumen of the connector is avoided. The tube portion  9  extends in its open form into the bag and comprises neither a one-way function nor a stool separation function. 
     Preferably, the balloon as well as the shaft tube of the head unit are made of an elastically deforming material with a preferentially low volume extensibility. For the balloon, especially thin-walled preformed balloon foils of polyurethane (PUR) are preferred, which provide the required combination of a geometrical stability during load and a low membrane-type wall thickness. An elastic expansion of the balloon envelope is not required and in the context of the invention conceptually rather undesirable. The balloon body is preferably filled with air, whereby it adopts in situ a slacky incompletely filled state, which ensures that the filled body in the rectum will, after a phase of adaption, attain a filling pressure, which in a good approximation corresponds to the respective intra-rectal pressure, and therefore allows a nearly pressure-neutral placement, which is comfortable for the patient. The balloon body is preferably formed as a dumbbell, whereby the middle tapered section of the balloon is placed in the anal channel. The balloon body is preferably extruded from a pre-extruded tube material, and in a subsequent step of blow molding shaped to the balloon. In a respective manner, the shaft element supporting the balloon body can be shaped from a pre-extruded foil tube to the required dimensions. Especially, the blow molding enables the shaping of a wavy, corrugated profile. 
     For both components, PUR types of hardnesses Shore 80A to 95A and 55D to 60D are deployed particularly advantageously, for example the type Pellethane 2363 of the company Lubrizol. 
     Furthermore, the invention describes a method for the washing of liquid substances or, respectively, of substances solved in a liquid into the colon of a patient, starting with the insertion of the patient&#39;s sided head unit  2  of the device into the anus, whereby the segment  3   b ,  3   c , which is tapered in its diameter, is placed in the region of the sphincter. Then, the entirely formed balloon  3  is filled with an amount of air, which is smaller than the freely unfolded, fully shaped volume of the balloon component. The balloon filled in this manner and clinging slacky to the rectum and anus absorbs the respective force in the rectum and uses it synchronously for the sealing in the anal channel, whereby the trans-anal segment of the balloon envelope follows the respective opening and closing state of the anus. The shaft element  4  supporting the balloon comprises the ability of a radial and axial, elastic folding and straightening. Then, the patient&#39;s sided portion of the device is closed by a closing function  19 . Subsequently, the connecting of the lavage-type bag for the preparatory cleaning or, respectively, lavage of the colon takes place. The bag comprises a throttling function as well as a stool separating function. Before the connecting, the lavage bag is closed by the closing function  19  and subsequently is filled up with the lavage fluid. After the opening of the closures on both sides, a lavage-type large fluid volume is instillated into the colon of the patient through a cycling procedure comprising a respective cyclic raising of the bag above and lowering it below the patient&#39;s level, which volume entirely comprises 1000 to 1200 mL of fluid, so that it reaches the transversal and potentially even the upper portion of the colon. Therefor, at least 1000 mL of fluid are displaced from the lavage bag into the colon in less than 30 seconds, preferably in less than 15 seconds. After repeting the cycle of inlet and outlet several times, the lavage bag is placed upside down and used as a collecting bag, which, during extended periods of time up to several hours, receives the parts of stool mobilized and drained belatedly after the lavage, without the fear of a perforating injury of the intestines through the head portion remaining in the rectum during the subsequent drainage. After the collection of the mobilized intestinal contents, the lavage bag is disconnected from the head unit, which remains inside the patient&#39;s rectum, and is disposed. The lavage-type cleaning of the colon can be repeated several times, whereby the lavage bag is exchanged each time or, respectively, is replaced by a fresh bag with fresh fluid. Thereby, the patient&#39;s sided part of the device remains inside the patient. 
     After completion of the preparative lavage of the colon, the bag for the lavage-type instillation of a therapeutical substance or of a transplant is prepared. It is terminally closed by means of the optional closing function  19 , then it is filled with the preparation and finally connected to the head portion of the device, which is inside the patient. Through the repetitive lavage-type introduction of the substance from the bag into the colon, analogously to the lavage, again the upper colon parts can be reached. The required flow rates are in the range of 1000 MI in 30 to 15 seconds. In difference to the lavage bag, the bag used for the introduction of the substance or of the transplant comprises a fixed or variably adjustable throttling function, but no stool separating function. After a completed repetitive cycle of inflow and outflow of the substance to be introduced, the preparation can remain inside the patient for a duration several hours, variably adjustable by the applicant, without any leakage of the preparation out from the anus. Thereby, the patient can adopt a comfortable, semisitting or sitting posture. For the final outflow of the preparation from the colon, the bag is lowered below the level of the patient and rests there until the substance is completely secreted.