Abstract:
A device for temporarily preventing flow of urine out of the urethra in a person suffering from urine incontinence comprises a first composition ( 11 ) enclosed in a first container ( 10 ) capable of being fed into the urethra ( 17 ) which is thereby blocked. The first container ( 10 ) comprises a mouthpiece ( 12 ) for insertion into the urethra ( 17 ) and for transport of the first composition ( 11 ) from the container ( 10 ) into the urethra ( 17 ). The first composition ( 11 ) comprises or is capable of forming a gel for blocking of the urethra by a gelatinous plug. The plug may be mechanically removed if the person wishes to urinate; alternatively the device may comprise a second composition in a second container for removal of the gel plug. In the latter alternative injection of the second composition in the urethra ( 17 ) adjacent to the gel plug causes the breakdown of the plug. Also disclosed is a corresponding method and the use of the first and second compositions in urine incontinence.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates to devices for use in urine incontinence, including a device for insertion into the urethra and the blocking thereof to prevent urine from passing the device. Devices of this kind are used to prevent urine leakage and unintended urination in men. The invention also relates to a packaged set of such devices, to a corresponding method for preventing urination, to a method for the manufacture of a composition for use in such devices, and to the use of such a composition.  
         BACKGROUND OF THE INVENTION  
         [0002]    There exist a great number of devices of various kind and design for coping with urine incontinence. Several of these devices are designed to be put on the penis; thereby urine is collected or urination is prevented. Such a kind of device is designed to clamp the urethra to thereby prevent leakage of urine.  
           [0003]    There is also a number of devices for coping with urine incontinence of which at least a portion are designed for insertion into the urethra. An device of this sort is shown and described in WO 97/13480. The device described in WO 97/13480 comprises a cover to be threaded on the glans penis. The cover is provided with a protruding portion for insertion into the urethra. When the user applies the cover onto the penis the protruding portion is inserted into the urethra and blocks it. The portion designed for insertion into the urethra thus is intended to prevent urine leakage by blocking the urethra in a way to prevent urine from passing.  
           [0004]    U.S. Pat. No. 5,671,755 A discloses an assembly for prevention of urinary incontinence in humans comprising an applicator and an expandable body comprising an appendage. The applicator is adapted to position the body in the urethra of a person. When the person wishes to urinate the body can be withdrawn by the appendage. Such withdrawal may however cause irritation in the terminal portion of the urethra since the body is removed in an expanded condition. The need for an appendage which extends from the mouth of the urethra is also problematic for hygienic and safety reasons.  
           [0005]    Except for the device disclosed in U.S. Pat. No. 5,671,755. A drawback with such devices for mounting on or insertion into the penis is that they may cause discomfort to the bearer since they are comparatively clumsy and affect the mobility of the bearer. A further drawback is that these devices are not so easy to use, in particular for elderly persons in whom incontinence is prevalent. In addition known devices for coping with urine incontinence may unintentionally glide off the penis, thus giving rise to urine leakage. Still another drawback are skin irritations which can arise due to portions abutting the penis. Also, there is a comparatively high risk of infection since the majority of known device are intended for repeated use. This problem is particularly evident with device intended for insertion into the urethra. A further drawback with these devices is that the blood flow in the penis and to the penis may be hindered which necessitates the removal of the device in regular intervals to restore normal blood flow to the penis.  
           [0006]    Another major problem with the majority of device for coping with urine incontinence known in the art is that they do not take into consideration differences between individuals. Such differences may, for instance, exist in regard of dimensions, thereby varying the fit of device intended for mounting on the penis or for insertion into the penis. This may result in reduced safety in regard of protection against incontinence or in other discomfort to the user. Consequently certain of these devices have to be adapted individually which is thought to result in high costs.  
           [0007]    A general problem with these devices is that they can only be used for coping with male incontinence for anatomic reasons.  
         OBJECTS OF THE INVENTION  
         [0008]    It is an object of the present invention to provide a device of the aforementioned kind, which is safe, easy to use, does not cause discomfort to the patient, and is cheap to produce, in particular if made disposable.  
           [0009]    It is another object of the invention to provide a device, which does not need to be adapted individually due to anatomical differences between the sexes and individual persons.  
           [0010]    It is an additional object of the invention to provide a corresponding method for coping with urine incontinence.  
           [0011]    Further objects of the invention will be evident from the following short description of the invention, a number of figures illustrating preferred embodiments thereof, which are described in more detail, and the appended claims.  
         SUMMARY OF THE INVENTION  
         [0012]    According to the present invention is disclosed an device comprising a device in form of a first composition comprising a gel enclosed in a first container. The container is provided with a mouthpiece and an outfeed means by which the first composition can be expelled from the container and fed into a urethra.  
           [0013]    It should be kept in mind that the container, the mouthpiece and the outfeed means can be designed in various ways and are not limited to the embodiments described herein. For instance, the container may be somewhat oblong and designed in a manner so as to be generally circular in cross section. The container may also be somewhat conical in form at the portion connecting it with the mouthpiece. Thus the container tapers off in the direction of the mouthpiece to facilitate pressing the composition out from the container and into the mouthpiece by means of the outfeed means.  
           [0014]    The mouthpiece is connected to the remainder of the container in a manner so as to enable the first composition to be fed out from the container through the mouthpiece by the outfeed means. The mouthpiece is suitably formed as an oblong tube generally circular in cross section and protruding from the container in a longitudinal direction thereof. Suitably the mouthpiece is designed in a somewhat conical manner so as to make the portion connecting the mouthpiece and the container having a somewhat larger diameter than the free end of the mouthpiece. The mouthpiece thus is designed for insertion into a urethra and for transport of the first composition from the container into the urethra.  
           [0015]    Suitably the outfeed means is disposed at aside of the container facing away from the mouthpiece. The outfeed means can take the form of an device for spraying out or pumping out the first composition in a conventional manner, whereby the composition can be fed out continuously or in given doses. The outfeed means can also be designed with a means for dosage control, whereby the doses can be adapted individually.  
           [0016]    The first composition is designed for transport from a first container to a portion in the urethra suitable for blocking. For instance, the first composition can be inserted about 10 cm into the urethra. The first composition comprises a gel or is capable of forming a gel when leaving the container or when abutting the urethra. Upon abutting the urethra the first composition exerts a pressure against the inner face of the urethra while a plug in form of a sphere or similar form for blocking of the urethra is being formed. The first composition preferably consists of tissue compatible components. The gel may be made expandable by, for instance, incorporation of a low boiling solvent, such as pentane or cyclopentane, or a suitable gas, such as butane or carbon dioxide, or a composition capable of forming such gas.  
           [0017]    The invention may also comprise a second composition enclosed in a second container. The second container may be designed in a manner corresponding to the first container. The second composition is designed for removal of the urethra blockage caused by the first composition. Thus the second composition is designed for being fed into the urethra and for dissolving the first composition upon coming in contact with the latter to allow the user to urinate without constraint. Residues of the first and second compositions, if present, are washed out when urinating, the urethra thereby being restored to its natural state.  
           [0018]    In case of, incontinence, in particular of male incontinence, the first composition may also be designed in a manner to allow removal of the urethra blockage by physical working thereof. By such physical working, for instance by working the outside of the penis, the blockage in form of the first composition is deformed and eventually pressed out of the urethra, whereby the blockage of the urethra is removed. Portions of the first composition possibly left in the urethra are washed out at urination.  
           [0019]    The first composition may comprise a composition of a chemical or biochemical nature, such as polysaccharide gels based on, for instance, agarose, dextrin, starch, cellulose and cellulose derivatives, such as hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl-methyl cellulose, hydroxyethyl-ethyl cellulose, hydroxypropyl-methyl cellulose, chitosan, xantan, alginate and derivatives thereof. Alternatively the first composition may comprise acrylate gels based on, for instance, acrylamide and its derivatives. The first composition may also be yielding, ductile, and biocompatible, may comprise bacteriostatic or bacteriocidal means, and may, by itself, constitute a barrier to bacteria. Furthermore the first composition may comprise properties promoting mucosal growth and thus may be designed in the form of a wound gel.  
           [0020]    The second composition may comprise a chemical mixture or solution comprising, for instance, a salt or a combination of salts, which counteracts the expanding (swelling) properties of the first composition and/or dissolves or degrades physically and/or chemically the first composition to remove the blockage formed by the first composition.  
           [0021]    In addition the second composition may have pH which, in contact with the first composition, counteracts the expanding (swelling) properties of the first composition. The second composition may also consist of various liquids the properties of which, such as surface tension, hydrophilicity, and viscosity can counteract the expanding properties of the first composition. It is also within the reach of the present invention to combine agents having the aforementioned properties for removal of the plug formed by the first composition.  
           [0022]    According to a first preferred aspect of the present invention is disclosed a set of devices for temporarily blocking an urethra comprising a first device containing a first urethral plug forming composition of the aforementioned kind and a second device containing second urethral plug removing composition, said devices being of the aforementioned kind. Suitably the devices of one set are enclosed in a sterile package. It is preferred for the mouthpiece openings of the devices to be sealed by a removable seal, in particular a seal that cannot applied again; thereby the devices are made obligatorily disposable and cannot cause infection of the urethra.  
           [0023]    According to a second preferred aspect of the invention the gel of the invention may be formed in situ by the reaction of two first composition components which are simultaneously and/or consecutively injected into the urethra, in particular by a device similar to that described above but having two chambers instead of one, each chamber holding one first composition component. The chambers are sealed prior to use to prevent the first composition components from mixing. After removal of the seal the first composition components are injected into the urethra in which they mix to form a first composition, which quickly turns to an expanding polymer plug; mixing may also occur in the distal portion of the device during or immediately prior to first composition component expulsion. For instance, one first composition component may contain the solution of a monomer, oligomer or pre-polymer whereas the other may contain a polymerization catalyst in solution. Alternatively one of the first composition components may be a polymer whereas the other first composition component may be a compound capable of reversibly reacting with said one of the first composition components, such as a monomer, oligomer or polymer possessing suitable reactive groups. Certain useful components may, for instance, be sensitive to heat and polymerize or condense at body temperature; in such case they have to be injected in at a temperature substantially below the body temperature. Temperature sensitive polymers for use in the invention are poly(N-vinyl amides), poly(N-alkyl acrylamides), poly(alkylene oxides) as well their random, block and graft copolymers with other monomers. Other useful components include pH-sensitive polymers which are soluble in a highly charged state but form gels if the pH is adjusted. Examples for this group are co-polymers of acrylic acid, metacrylic acid, hyaluronic acid and chitosan. Useful systems incorporating two components comprise poly(vinylalcohol) and borate/boronate containing compounds, polymers capable having a ligand capable of interaction with a polymer of a different kind. An example for such systems is one comprising a polymer having chelating groups complexed by two- or multivalent metal ions and a histidine rich polymer or the couple polymer carbohydrate/lectin or a polymer with antigen moieties linked thereto capable of binding to antibodies linked to another polymer or to free antibodies. Combinations of these systems are also within the scope of the present invention such as, for instance, a precipitation induced by a change in temperature followed by reaction of the precipitated polymer with another polymer.  
           [0024]    According to a third preferred aspect of the invention are disclosed corresponding suitable first and second compositions. 
       
    
    
     SHORT DESCRIPTION OF THE DRAWINGS  
       [0025]    The invention will now be explained in more detail by reference to drawings, in which  
         [0026]    [0026]FIG. 1 is a general view, in a longitudinal section, of a first composition enclosed in a first container, illustrating a first embodiment of the container;  
         [0027]    [0027]FIG. 2 is a general view, in a longitudinal section, of a first composition enclosed in a first container, illustrating a second embodiment of the invention;  
         [0028]    [0028]FIG. 3 is a partial view, in a longitudinal section, of the insertion of the device of FIG. 2 into an urethra of a male person, after expulsion of the first composition and formation of a plug, the device not being shown in section;  
         [0029]    [0029]FIG. 4 is a partial view, in a longitudinal section, of the insertion of a device corresponding to the device of FIG. 2 but filled with a second composition, after expulsion of the second composition and its action on the urethral plug formed by the first composition, the device not being shown in section;  
         [0030]    [0030]FIG. 5 is a general view of a third embodiment of the invention with two chambers filled with a first and a second fluid capable of forming a first composition on mixing, in a longitudinal section. 
     
    
     DESCRIPTION OF PREFERRED EMBODIMENTS  
     EXAMPLE 1  
     Devices  
       [0031]    By reference to the Figures, in particular FIG. 1 and FIG. 2, is illustrated a first embodiment of the device according to the invention comprising a first container  10  comprising a mouthpiece  12  and holding a first plug forming composition  11 .  
         [0032]    It should be noted that thickness dimensions of materials, distances between various components, and other geometric relationships are not to scale in the Figures. Furthermore the container  10 , in particular, may be designed in various ways and is in no way limited by the embodiments described herein. Preferably the container  10  is made of a flexible polymer material, such as polyethylene or polypropylene.  
         [0033]    The container  10  of FIG. 1 is oblong and has a generally circular cross section; it is closed at its one (proximal) end and open at its other (distal) end. Its rear portion forms a first opening  14  at which it merges with the wall of the mouthpiece portion  12 . By its viscosity the first composition  11  is essentially kept in the rear portion of the first container  10 . The rear portion of the container  10  is designed biconically to facilitate the transfer of the first composition  11  to the mouthpiece  12 . Thus the rear portion of the container  10  tapers off towards the first opening  14 . The mouthpiece  12  protrudes distally from the rear portion in the longitudinal direction of container  10 , forming a narrowed extension of a generally circular cross section. At its free (distal) end the mouthpiece  12  comprises a second opening  15 , through which the first composition  11  can be expelled from the container  10 .  
         [0034]    The mouthpiece  12  tapers off in the direction of the second opening  15 . The mouthpiece  12  is designed for partial insertion into the urethra; see, FIGS. 3 and 4. The second opening of the mouthpiece  12  is preferably provided with a seal  21  to keep the first composition  11  sterile and to prevent the first composition from leaving the container  10  prior to use. The seal  21  is arranged in a manner so at to make the seal  21  removable prior to the application of the first composition  11 . The seal  21  can be designed in any conventional manner. It is intended to be removed before applying the first composition. For instance, the seal  21  is integrated with the mouthpiece  12  and is removed by tearing it off. The seal  21  may also take the form of a distal end portion integral with the mouth piece  12  and joined to the latter at a circular kerf; in such case the opening  15  is formed by breaking off said distal end portion.  
         [0035]    The first composition  11  in the container  10  shown in FIG. 1 can be expelled by compressing the container  10 . The container  10  holds an amount of the first composition  11  suitable for at minimum a single administration. The container  10  may be designed as a disposable package.  
         [0036]    The second embodiment of the container  10  shown in FIG. 2 in which the same reference figures are used for elements corresponding to those of the embodiment of FIG. 1 comprises an outfeed means  13  in form of a piston. The outfeed means  13  is disposed in the cylindrical rear (proximal) portion of the container  10 ′ in a manner corresponding to that of a piston in a syringe for injection. By pushing the pusher of the piston  13  in a distal direction the first composition  11 ′ is expelled from the container  10 ′. It may be fed out continuously or in selected doses, which can be determined by a means of a marking  22  applied on the piston  13  or on the container wall which, in such case, has to be transparent. The dosing can be adapted individually according to the desire of the user.  
         [0037]    Now referring also to FIG. 3, the mouthpiece  12 ′ of the first container  10 ′ is disposed in the end portion of a urethra  17  in a penis  16 . The disposition of the mouthpiece is that required for feeding the first composition  11 ″ to a correct position in the urethra  17 . The mouthpiece  12  is inserted into the urethra  17  via the mouth of the urethra at the glans  18  penis  16 . Usually insertion to a depth of about 10 mm will suffice. In FIG. 3 is shown a state in which a portion of the first composition  11 ′ has been expelled from the container  10 ′ and a plug  20  has been formed. Upon feeding the first composition  11 ′ into the urethra the mouthpiece  12 ′ is removed from the urethra  17  (not shown).  
         [0038]    The first composition  11 ′ is placed in the urethra at a certain depth for blocking the urethra. Thus the first composition  11 ′ abuts the inner face of the urethra  17 . By gel formation and, possibly, expansion of the first composition  11 ′, the first composition  11  presses against the inner face of the urethra  17 , whereby the first composition  11 ′ can assume a generally spherical form. The abutment of the first composition  11 ′ against the inner face of the urethra  17  and the expanding properties of the first composition  11 ′ result in the blocking of the urethra  17  which prevents urine from passing the first composition  11 .  
         [0039]    The first composition may comprise chemical compositions such as polysaccharide gels based on, for instance, agarose, dextrin, starch, cellulose, alginate, xanthan or chitosan and derivatives thereof. Alternatively the first composition  11  may comprise acrylate gels based on, for instance, acrylamide or derivatives thereof. In a preferred embodiment the first composition is an alginate gel. Suitably the first composition is yielding, ductile, and biocompatible, and may comprise bacteriostatic agents, which can form a barrier against bacteria. Furthermore the first composition may comprise properties that promote growth of the urethral mucosa.  
         [0040]    A further embodiment of the present invention is shown in FIG. 4. A second container  19  containing a second composition  20  is arranged for feeding the second composition  20  into the urethra  17 . The second container  19  can be designed similar to the first container  10 , and thus comprises a mouthpiece  12 ″ and an outfeed means such as described above in connection with the first container  10 .  
         [0041]    The second composition  20  is designed for being fed into the urethra  17 . Thus the second composition is fed into the urethra at or near the blockage to bring it in contact with the latter, whereby the blockage is removed by dissolution of the plug formed by the first composition  11 ′. Alternatively the second composition  20  may comprise properties, such as shrinkage inducing properties, which oppose the expanding or gel stabilizing properties of the first composition  11 ′, whereby the blockage can be removed after shrinking of the plug. The second composition may comprise a chemical composition of a combination of various salts. Furthermore the second composition  20  may have a pH-value which, in contact with the first composition  11 ′, counteracts the plug retaining properties of the first composition  11 ′. The second composition  20  may also consist of various solvents of which properties like surface tension, hydrophilicity, and viscosity can counteract the expanding or gel stabilizing properties of the first composition  11 ′.  
         [0042]    Thus the second composition  20  is designed for being fed into the urethra  17  and to contact the first composition. These results in the first composition  11 ′ being dissolved or degraded or diminished in size by shrinkage, which allows the user to urinate if so desired. On urinating rests of the first and second compositions  11 ′, if any, 20 are removed, whereby the urethra is reconstituted.  
         [0043]    In an embodiment of the present invention the first composition  11 , 11 ′ can also be designed in a manner to let the blockage of the urethra  17  caused by the first composition  11 , 11 ′ be removed by certain physical working. By this physical working, in particular of the outside of the penis  16 , the blockage in form of the first composition  11 , 11 ′ is pressed out, whereby it changes its form so that the blockage of the urethra is removed. When urinating the first composition  11 , 11 ′ is then driven out from the urethra  17  by the urine.  
         [0044]    The embodiment shown in FIG. 5 is a device  30  according to the invention provided with first and a second chambers containing a first fluid  37  and a second fluid  38 . The fluids  37 , 38  contain components which are capable of forming a first gelatinous composition on mixing. The first and second chambers are enclosed by a common rotationally symmetric wall  31  extending from a circular rear wall  34  in a distal direction in which the outer diameter gradually diminishes over an intermediate wall section  32  which to which a mouthpiece section  33  ending in a mouthpiece  39  is joined. The rear wall  34  is provided with a peripheral circular flange  35  and is integral with wall sections  31 ,  32 ,  33  and a flat inner wall  36  disposed between the first and second chambers. The inner wall  36  does not extend to the mouthpiece  39  but ends a little proximally of it. The distal end of the inner wall  36  is capable of being received in a proximal slit of a sealing stopper  45 , which seals the first and second chambers from each other as well as the mouthpiece  39  and is removed prior to use. The first and second fluids  37 , 38  are expelled from the device  30  at the same rate by first  44 , 41  and second  43 , 42  plungers, respectively, the rods  41 , 42  of which are sealingly (not shown) guided in openings of the rear wall  34  and are joined by a transverse pusher  40  at their proximal end. This provides for their concerted displacement when pushed in a distal direction to expulse the first and second fluids  37 , 38  from the respective chambers. As explained for the other embodiments the mouthpiece  39  can be inserted into an urethra after removal of the stopper  45  into which the first and second fluids can be injected simultaneously. By making the inner wall  36  end at a distance proximal of the mouthpiece opening a terminal space is formed in the mouthpiece  39  adjacent to said opening in which the first and second fluids partially or fully mix before leaving the mouthpiece. Mixing can be improved by, for instance, arranging mechanical means, which make the flow to become turbulent, in the terminal space, such as ribs disposed on the inner wall of the space (not shown). As is evident from the foregoing the first and second chambers and the plunger heads  44 , 43  are semicircular in a transverse section.  
       EXAMPLE 2  
     Compositions  
       [0045]    A preferred embodiment of the first composition is based on the complex formation between boronate groups and polyol compounds. Poly(vinyl alcohol) (PVA) has been used as a polyol, and copolymers of and N-acryloyl-p-aminophenylboronic acid as a source of boronate groups, the following called boronate polymer. The complex formation between two polymers of this kind results in gel formation. A preferred embodiment of the second composition comprises glucose. Glucose competes with PVA for boronate groups. This results in the boronate-PVA bonds responsible for the attraction between two polymers being broken, and in the dissolution of the free polymers thus formed.  
         [0046]    The model polymer system of the first composition forms is capable of quickly forming a gel which is sufficiently dense to stay in the urethra for extended periods of time, such as one hour or more, thereby occluding the urethra and preventing leakage of urine. On the other hand the gel plug formed by the first composition is relatively fast dissolved on addition of glucose or another suitable low-molecular-weight saccharide. The gel formation of poly(vinyl alcohol) (PVA) with borate polymer proceeds at a high rate at alkaline conditions (pH&gt;9.5), whereas the dissolution of the gel proceeds at a high rate in a solution containing 1% by weight of glucose at pH 3. The PVA-gel of the invention was formed within seconds after mixing an aqueous PVA solution with an aqueous borate polymer solution, and was dense enough to prevent water flow through a tube at a pressure of about 50 cm of water column. The gel dissolved within 10-15 min when immersed in 1% glucose solution, pH 3.  
         [0047]    Instead of gel formation with boronate polymer the effect of 0.1M Na 2 B 4 O 7  (pH 9.8) on aqueous PVA solutions of varying content was studied. A PVA concentration of 3% w/v was sufficient for gel formation, while the lower concentrations (≦2%) did not give a gel or a visually noticeable increase in solution viscosity. Decimolar sodium tetraborate (pH 9.8) or its mixtures with 0.4 M boric acid (pH varying from 7.1 to 8.5, 0.5 ml) were added to a 5% w/v aqueous solution of PVA (0.5 ml) in a vial immediately followed by shaking to mix the solutions. Gelation was visually estimated by turning the vials upside down 1 min, 3 h, and 24 h after mixing. Efficiency of gelation was designated as follows: − (no gelation), −/+ (incomplete gel formation; separation of the mixture into phases with lower and higher viscosity) +/− (quick gel formation followed by gradual collapse of the gel and appearance of a liquid phase in a few hours), + (stable gel after 24 h). The results are summarized in Table 1.  
                                     TABLE 1                           Gelation of boronate buffer       solutions with PVA as a       function of pH                pH 7.1   pH 7.8   pH 8.5   pH 9.8                       −   −/+   +   +                      
 
         [0048]    As follows from Table 1 efficient gelation of boronate buffers with PVA is possible in basic media, where a certain share of boronate ions is present in charged tetrahedral forms. Lowering of boron concentration from 0.4 to 0.2 moles/l led to a weaker gel-formation (−/+ type) at pH 8.5.  
         [0049]    Copolymer of N,N-dimethylacrylamide (DMAA) and N-acryloyl-3-aminophenylboronic Acid (AAPBA)  
                         
 
         [0050]    Synthesis of AAPBA. 3-aminophenylboronic acid hydrochloride (3-APBA) (1.72 g, 10 mmol) was dissolved in 20 ml 2M NaOH (40 mmol). The solution was filtered and cooled to 3° C. in an ice bath. Acryloylchloride (1.6 ml, 20 mmol) was added drop-wise to the solution of 3-APBA while intensively stirring for 5-6 min. HCl (2 M) was added drop-wise to the reaction mixture to adjust its pH to about 1. The precipitate was separated by filtration on a sintered glass filter (Schott, Duran, No.3) and washed with distilled water (50 ml). The washed precipitate was dissolved in 40 ml distilled water at 60° C. from which it crystallized overnight at 8° C. as light-violet needles. The crystals were filtered off, washed with cold distilled water and dried under vacuum in a desiccator over CaCl 2 . The yield of AAPBA was 0.76 g (40%).  1 H NMR (CD 3 SOCD 3 ): δ=5.73 (1H, a), 6.25 (1H, b), 6.45 (1H, c), 7.2-7.9 (4H, d), 8.0 (2H, e), 10.05 (1H, f).  
         [0051]    Boronate-containing polymers. Two samples termed pac-B1 and pac-B2 were prepared by free-radical copolymerization of DMAA and AAPBA. Commercial DMAA was separated from hydroquinone monomethyl ether (polymerization inhibitor) by flash chromatography on a 0.9×2.5 cm column packed with dry activated aluminum oxide; 3 ml of the starting material gave 1.9 ml of pure DMAA.  
         [0052]    Pac-B1. DMAA (0.93 ml, 9 mmol) was dissolved in 5 ml of dioxane. AAPBA (190 mg, 1 mmol) was dissolved in 4 ml of dioxane by heating to 70° C. The monomer solutions were combined in a beaker and mixed, followed by dissolving 20 mg of 2,2′-azobis(2-methylpropionitrile) (AIBN) in the mixture. Free radical polymerization was started by heating the mixture under N 2  to 70° C. for 30 min. The gelatinous copolymer formed was dissolved in 8 ml of ethanol, and the solution was added drop-wise to 100 ml of diethyl ether to precipitate the copolymer. The precipitate was collected by filtration, washed with diethyl ether and dried under vacuum; yield 0.40 g (37%).  
         [0053]    Pac-B2. DMAA (0.93 ml, 9 mmol), AAPBA (190 mg, 1 mmol) and AIBN (10 mg) were dissolved in 10 ml of ethanol. Free radical polymerization was started by heating the reaction mixture under N 2  to 70° C. and keeping it at that temperature for 6 h. The thus obtained solution of copolymer was added drop-wise to 100 ml diethyl ether to precipitate the copolymer. The precipitate was collected by filtration, washed with diethyl ether and dried under vacuum; yield 0.87 g (77%).  
         [0054]    The pac-B1 and -B2 polymers were characterized by  1 H NMR, and the molar fractions of AAPBA-units, m/(m+n), were quantified as 12 mol % and 8 mol %, respectively. The calculation was performed according to formula: m/(m+n)=(d+e)/(c+d+e) or m/(m+n)=(d+e)/6: [(d+e)/6+a/2] which gave similar results.  
         [0055]    Although the copolymers were closely related in regard of their chemical composition, their solubility in water was found to be substantially different: pac-B2 easily dissolved in distilled water at any pH, while pac-B1 was only soluble under basic conditions. Presumably, the higher content of AAPBA units makes the PAC-B1 copolymer more hydrophobic so that it could only be dissolved if its boronate functions became partially charged at higher pH.  
         [0056]    Gelation of PVA with pac-B1 or pac-B2. Equal volumes of the solutions were mixed at various pH. Results are summarized in Table 2.  
                                         TABLE 2                           Gelation of the boronate-containing copolymers with       PVA as a function of pH                Sample   PH 5.7   PH 7.0   PH 8.1   PH 8.5                       Pac-B1   Not   Not   2%: −/+   1%: +               soluble   soluble       2%: + or                           +/−           Pac-B2   1%: −   1%: −   1%: −   1%: −               2%: +/−   2%: +/−   2%: +/−   2%: + or                           +/−                      
 
         [0057]    As follows from Tables 1 and 2, pac-B2 is capable of gelation with PVA over a much wider range of pH compared to the low molecular weight boronates. The underlying reason is probably a multipoint binding of the copolymers to PVA. If at least two charged boronate functions belong to a single polymeric chain, it may react as a macromolecular crosslinker of PVA.  
         [0058]    It is worth to note that gelation of PVA with the boronate-containing copolymer proceeds at a much lower boron concentration in the solution compared to low molecular weight boronates: 0.015 g-atom/l (2% w/v pac-B2) against 0.4 g-atom/l (0.1M Na 2 B 4 O 7 +0.4M H 3 BO 3 , 1:1, pH 8.5). This is another evidence for the efficient macromolecular crosslinking of PVA by the boronate-containing copolymers. The gels formed were easily dissolved in 1% glucose solution, pH 3.