CS197409B1 - Hydrophilous pipe preparation determined for introducing in the body cavities and method of making the same - Google Patents

Description

The invention relates to hydrophilic tubular formulations, i.e. instruments intended for introduction into body cavities, i.e., hydrophilic catheters, oculars, tracheal, gastric, vascular or the like, intended for intubility to provide patency or examination, taking body secretion samples, optionally to perform medical interventions.

For brevity, these preparations as instruments will hereinafter be referred to as catheters according to their most common use.

As the state of the art is to mention MS. No. 163539, which discloses one possible method of manufacturing elastic hydrogel tubes, which may be a starting material for the manufacture of the preparations or tools of the invention. The method consists in extruding a solution of the hydrophilic copolymers in a suitable solvent, e.g., concentrated nitric acid, into the water through a circular nozzle with a central water supply. Another method of production of hydrogel tubes - by hot swelling of the swollen hydrogel by a screw press is described in Czech. No. 175082. The urological gut and its method of production from the thus obtained hydrogel tubes are then the subject of MS. Certificate No 173836,

The hydrophilic catheters prepared according to the above-mentioned authors certificates are progressive against hydrophobic catheters because of their overall smoothness and thus compatibility with living tissue or mucous membranes and the possibility of incorporation of biologically active substances such as antibiotics, anesthetics and the like. On the other hand, they have a number of problems with sterilization, storage and the like, since they have to protect themselves from drying out. Also, sterilization causes some difficulty since it swells strongly, resizes, and the like, and during chemical sterilization, the sterilizing agent penetrates into the gel structure from where it is difficult to remove and can complicate application.

The part of the catheter, probe, etc. that is inserted into the body cavity (ureter, trachea, bile duct, esophagus, gastrointestinal tract, respiratory tract, etc.) usually does not dry out and does not cure when applied. On the other hand, those parts that protrude from the body cavities are swollen in the air

197 409

197 409 lose their flexibility and reduce their dimensions, so they must be protected from dehumidification.

This can be done either by using a hydrophobic tube (eg plasticized polyvinyl chloride, natural or silicone rubber) as a catheter, and forming a hydrophilic polymer (eg partially hydrolyzed polyacrylonitrile, sparsely cross-linked polyglycol methacrylate, polyvinylpyrrolidone, polyvinyl acrylamide, etc.) .) a coating from the catheter to the height that is intended to be inserted into the body cavity. Alternatively, a catheter end may be formed from the same hydrophilic polymer. Thus, the second cone protruding from the cavity is made only of a hydrophobic polymer. Another way is to coat the outer cone of the catheter (i.e., one that will protrude from the body cavity) with a layer of hydrophobic polymer that protects the hydrogel from the outside of the catheter from drying out. Both of these solutions have the disadvantage that the length of the part of the catheter which is intended to be inserted into the body cavity, e.g. the urethra, is fixed in advance, and the catheter generally cannot be inserted because the hydrophilic and hydrophobic polymer interface painfully hurts the mucosa. and if the catheter were less inserted, its unprotected part would dry out and harden, so in addition to the diameter, it would be necessary to specify another parameter in these catheters - the length of the part to be inserted into the body cavity. available, and the insertion depth can not be changed according to immediate needs except for the corner. Apart from these disadvantages, however, the problems of storage, transport and packaging of hydrophilic catheters remain unresolved.

These defects are eliminated by the hydrophilic formulation as a tool for insertion into the body cavities, hereinafter referred to briefly as the catheter, according to the invention, characterized in that the catheter is formed of or provided with a hydrogel on its surface which comes into contact with the surface the body cavity and in the swollen and sterile state is enclosed in a removable flexible package. Optionally, between the catheter and the sheath is a cavity filled with a sterile physiological solution that also fills the interior of the catheter. This cavity separates from the catheter that portion of the flexible container to be removed before use. The wrapper is preferably weakened at the point where it is to be torn, for example by a notch or glued fiber whose cone protrudes onto the surface of the hydrophilic composition.

The resilient wrapper in the form of an elastomeric tubing whose inner diameter is less than the outer diameter of the catheter in the unrotated state, is preferably stretched onto the water-swollen catheter so that it swells in advance in a volatile solvent or shoe, thereby increasing its diameter 1. After stretching, the solvent or shoe is evaporated or scrubbed until the hydrophobic resilient sheath contracts to its original diameter.

Outer tube of elastic material, such as plasticized polyvinyl alcohol, polyvinyl acetate, polybutadiene, polyisoprene, polyohloroprene, styrene-butadiene or acrylonitrile-butadiene-styrene rubber, silicone rubber, halosulfonated polyethylene, poly (ethylene-copolymer), poly (ethylene copolymer), ethylene copolymer, ethylene copolymer, ethylene copolymer. several funkoit

During storage and transport, they serve as a perfect protection for the hydrogel part of the catheter from drying out and its contamination by bacteria or fungi, so that the inner part of the catheter, intended to be inserted into the body cavities, can be kept sterile and ready for use. Can the catheter hydrogel part be sterilized _? before dragging the outer impermeable tube over the hydrogel, for example with ethylene oxide, Rivanol solution or the like, or preferably by sterilizing the hydrogel at both ends with an oxidizing agent such as hydrogen peroxide or alkaline hypochlorite prior to sealing the outer protective tubing a reducing agent (e.g., ascorbic acid) in excess to convert the oxidizing agent into harmless products (in the examples, water or alkaline chloride, respectively). In such a case, the hydrogel inner tubing is filled with water, or preferably an isotonic saline solution such as NaCl.

Alkaline hypochlorite can be used for chemical sterilization just in such a quantity that the chloride resulting from it just replenishes the concentration of salts in the isotonlocal solution to the required value (eg 0.9% by weight of NaCl). The oxidizing sterilizing agent and the reducing component may be introduced into the catheter prior to closing the outer tubing and at the same time if they dissolve sequentially, eg in the form of a tablet whose inner part contains ascorbic acid and the outer which dissolves in advance contains alkaline flame. Dissolution of both

The 197,409 components can be further separated in time by, for example, providing the inner part of the tablet containing the reducing agent with a coating of a water-soluble or strongly swellable polymer which retards the dissolution of the reducing agent.

However, in addition to these two-component sterilizing agents, sufficiently effective yet harmless agents such as Rivanol, antibiotics and the like can also be used. Finally, the catheter can be sterilized after closure as a whole by radiation or by heating to + 100 to 125 ° C.

Prior to insertion of the hydrogel portion of the catheter, the required insertion depth is measured and at this point the outer protective tube is cut with a sharp tool (eg, knife, scalpel or shaving blade) and the outer tube is removed from the hydrogel inner tube to expose the atraumatic and sterile surface. Estimation and measurement of the cutting position can be facilitated by a marked degree on the outer surface of the outer protective tube. The contraction of a portion of the protective outer tube may advantageously be facilitated by its longitudinal incision. The longitudinally slit portion of the outer protective tube further serves to temporarily prevent either part of the catheter from drying out (when insertion depth needs to be reduced during application) or the entire catheter after removal, if desired to be reused after thorough sterilization.

The second, i.e., the outer end of the catheter is opened in a similar manner prior to use, the obtained portion of the closed outer tube preferably serving as a sterile catheter plug. Therefore, the closure is preferably performed such that the non-swellable polymer plug partially extends into the inner hydrogel tube, and the outer tube is cut off just beyond the outer end of the hydrogel tube. Where the catheter opens only temporarily and for a short time, as is the case with urethral catheters, cuts can be made where the hydrogel is already underneath the outer tube and the catheter can be closed by re-inserting the outer blind tube onto the short-term exposed hydrogel end of the catheter. .

Cutting the outer tube and removing it from the hydrogel generally does not cause any problems, but can be facilitated by cutting and sealing the outer tube at the predicted cuts, inserting a fiber, string, etc. into the bonded or possibly welded joint, and at least one free end projecting above the surface. Then, instead of cutting, the required part can be separated by pulling the glued or welded filament, or strings, etc., that cut the joint. The same fiber can also advantageously be used to secure a separate portion of the outer tube, which remains loosely connected to the catheter and is readily accessible for reuse as plugs or desiccant protection. Joints with glued fiber may be at multiple locations of the predicted cuts, of course not all of them must be used.

The removal of part of the outer catheter tubioe is easiest for catheters whose outer hydrogel surface is strongly hydrophilic (so-called superhydrophilized, eg according to the author's certificate No. 163539 by the action of glycerol and concentrated sulfuric acid), which are at the same time most advantageous for their high atraumaticity. The polymer in such a superhydrophilic surface layer comprises more than 90, or even more than 95% by weight. water. Under this surface, of course, there must be a layer of less hydrophilic polymer containing, for example, 20 to 80% by weight. water which imparts to the catheter a degree of stiffness necessary for insertion of the catheter and in order not to close the cross-section of the catheter during use. The rigidity of the catheter may also be provided by a tube of elastic hydrophobic polymer (butadiene or silicone rubber, softened polyvinyl chloride, etc.), which is further drawn by a hydrophilic tube (optionally hydrophilized on the coating) and finally externally by an elastic protective thimble. The inner hydrophobic tube is particularly advantageous where the permeation of some low molecular weight substances through the catheter wall would be impeded (e.g., it is desirable for a feeding probe to allow the drugs and possibly anesthetics incorporated in the gel layer to penetrate the tear fluid in contact with probe, but not food supplied).

If the outer layer of the hydrophilic portion of the catheter is highly hydrophilic (superhydrophilized), the outer protective layer slides very easily over it so that it can be easily pulled off without longitudinal slit, and that portion of the outer protective layer that protects the protruding portion of the catheter from drying move the gel tube quite freely. This is advantageous where we need to readily change the insertion depth during application, but on the other hand, this mobility of the outer layer makes it difficult to fix the catheter. Therefore, it is preferred that the hydrogel inner tube have a highly hydrophilic slippery surface only at a length that is the maximum expected catheter insertion depth, whereas that part of the hydrogel tube that will certainly be outside the body is less hydrophilic or, ultimately, hydrophobic. This ensures that the remainder of the protective outer tubioe does not move when applied even at higher loads, the portion of the outer tube remaining after removal of the other tubioe parts at both ends of the catheter serves both to protect the hydrogel from drying out and to fix the catheter during application. This part of the catheter can be conveniently adhered, for example, with adhesive tape that does not adhere to the hydrophilic surface of the catheter. In addition, this part of the protective outer tube is also suitable for marking catheter properties (eg diameter, stiffness, type, etc.) since marking directly on the hydrogel is difficult.

The advantages of the catheter of the invention over previously known types of hydrophilic surface catheters are evident from the following description. The catheter of the invention is stored and transported as easily as a conventional catheter of hydrophobic resilient materials, facilitated in sterilization, ready to use at any time, and can be inserted at any depth between the maximum and minimum values given by the basic dimensions of the catheter, the protruding portion is securely protected from ejection. Another advantage is that the catheter cap is readily available at its outer end and the wrapping is provided to protect it from extending its inner end after temporary removal from the body cavity. In addition, the hydrogel portion can be swollen with isotonic or drug solutions during storage without the need for expensive and heavy watertight containers. Thus, the catheter of the present invention combines the advantages of the prior art hydrophilic and hydrophobic catheters.

The manufacture of the catheters according to the invention is only slightly more complex and expensive than the production of the prior art hydrophilic catheters of the corresponding design, since the following additional operations are necessary:

1. For pre-fabricated hydrogel tubing, optionally partially or zoologically further hydrophilic, and optionally provided with a suitable rounded end, side outlets and the like, and optionally strung or directly made on the inner tubing of elastic hydrophobic polymer, select tubing of hydrophobic elastic polymer, which has na5

197,409 of the same diameter as the hydrogel tube, but preferably 5 to 50% smaller and at least as long as the hydrogel tube;

2. swell the selected hydrophobic tube in a suitable solvent or temporarily deform it at elevated temperature so that its diameter is temporarily larger than the diameter of the hydrogel tube · Some tubes are available from the factory in such a deformed form, eg · plasticized polyvinyl chloride;

3 · Thread the hydrophobic tube of temporarily enlarged diameter over the hydrogel tube so that the outer tube protrudes through the hydrogel part at both ends;

By removing at least a part of the solvent or plasticizer by evaporation or washing with the solvent or by briefly heating to at least the temperature of the previous deformation, the diameter of the outer tube is reduced, thereby firmly adhering to the hydrogel surface;

5) seal the outer protective tube at both ends, for example by sealing or sealing the ends, soaking the ends in a solution or melt of a hydrophobic and preferably elastic polymer, or by gluing or fusing plugs of such a material. Chemical sterilization may be performed before closure at both ends as described above. A somewhat less preferred alternative to this procedure is to reduce the diameter of the hydrogel tube by partially drying or swelling in a worse boot than water, then drag the outer tube and rewind the hydrogel in water dimension · The end result is the same for both procedures; however, the second alternative is somewhat more laborious.

After closing both ends of the outer tube, the catheter can be treated as a common hydrophobic type, ie * can be printed, surface sterilized with ethylene oxide, packed and stored as a conventional rubber catheter · Printing, temporary incision of the outer tube at predicted incisions and fiber sticking usually at any stage of the production process ·

Some types of catheters and methods for their manufacture are described in the following examples, supplemented by corresponding drawings.

1 shows a schematic representation of a hydrogel catheter even in longitudinal section through which a silicone rubber tubing having a wall of about 0.2 mm thick is passed as a resilient casing 2. Between them, the space 2 is filled with sterile saline. The container 2 closed removable plug £, £ even before the conclusion of a physiological saline was injected into the package P 2 ° ^d slight overpressure in order to create space between the catheter 2 and the portion of the flexible sheath 2 »which is removed before use.

Giant. 2 shows a cross-section through a catheter 1 with two parallel passages 24a of unequal cross-section usable as a urethral occluder or a tracheal intubation probe. The outer hydrogel tube J is provided with a slipper, a highly hydrophilized layer over which the outer flexible hydrophobic removable sleeve 8 is threaded.

Giant. 3 is a longitudinal sectional view of the catheter of FIG. 2 with a fixation balloon. This type of catheter is described in detail in Example 3.

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Example 1 wt. parts of acrylonitrile was dissolved in 85 parts of 65% dicalic acid and polymerized by addition of 0.01% ammonium persulfate at 20 ° C. After 70 hours, when the polymerization conversion reached 92%, 79% sulfuric acid (96 µl) was added, calculated per oil mixture. The solution was then left at + 15 ° C for an additional 30 hours. The viscous solution was extruded through a circular nozzle with central water supply to the aqueous coagulation bath to form 4 mm diameter hydrogel tubes, 1.5 mm wall thickness, containing 62% water at equilibrium swelling. The tube was cut into pieces 20 cm long which were cut at a 45 ° angle and loaded for 40 hours in glycerin containing 10% water.

Then, the tubes 1 were immersed for 11 minutes in 96% sulfuric acid + 55 ° C warm enough to form a layer of highly swollen polymer over a length of 15 µm. After washing and neutralization with dilute sodium bicarbonate solution, tube X was placed in physiological saline containing 0.5% sodium hypochlorite. After removal from the physiological solution, a tube 2 of silicone rubber, a wall thickness of 0.2 mm and an initial diameter of 6 mm was pulled over the X tube so that it was first swollen in ethyl acetate to a diameter of 10 mm so that it can be easily threaded onto the X hydrogel tube. after evaporation of the ethyl acetate at 40 ° C, the silicone tube 2 shrank to their original diameter and adhered strongly to the surface of the hydrogel · Then, the silicone tube ²¹¹⁶ one meter terminal position sealed with a silicone auto-cured composition, hydrogel tube X silicone coating charged with 2-HIM aqueous sterile solution of ascorbic acid The second cone of the outer tubing 2 was then sealed in the same manner. Tube X was suitable as a tracheal probe, prepared after removal of the necessary portion of the outer silicone tube 2 under aseptic ocular conditions for immediate use (a schematic cross-section through the steel kit is shown in Figure 1).

Example2

A natural rubber urological catheter, provided with a conical side opening closer to the conical cone, was swelled in a 5x solution of glycidyl methacrylate in toluene until the volume was increased by 50%. It was then soaked in a solution having a viscosity of 11.5 Pas of this composition: 80% methanol,% uncrosslinked hydroxyethyl methacrylate polymer, 7% hydroxyethyl methacrylate monomer containing 1% ethylene glycol dimethacrylate, 2.9% diaoetine and 0.1% cumene hydroperoxide. The excess solution dripped off and after evaporation of the methanol in air an approximately 0.5 mm thick coating of the uncrosslinked hydroxyethyl methacrylate polymer softened with monomer and diaoetin to the viscoelastic state was formed on the ocular surface. Thereafter, the temperature was raised to + 100 ° C under vacuum to polymerize the added monomer, the catheter was washed in water and swollen in an aqueous solution of chloramphenicol. Then, a rubber tube swollen in n-hexane was passed through an oil catheter, and the two tubes were glued together with a solution of rubber in toluene. Then the tubing was cut across the entire circumference and a polyamide horsehair was inserted into each section so that its ends protrude from the section, and the horsehair sections were again sealed with a solution of rubber in toluene. After the glue had dried, the collar and the outer packaging were sealed in polyethylene foil packaging and the whole set was sterilized by gamma-radiation, which caused

197,409 and other crosslinking of the hydrogel layer and its direct connection with the inner rubber tube of the catheter.

Prior to use, the outer rubber wrapper could be opened at any point by pulling on the protruding cone of the polyamide horsehair and the urological catheter used for further sterilization or other treatments.

Example 3

From the solution of partially hydrolyzed polyacrylonitrile according to Example 1, tube X with two parallel passages was extruded (shown in cross-section in Fig. 2). On the same device but with a single circular central water inlet, it was then from above hydrolyzed polyacrylonitrile with equilibrium swelling. % of the water extruded a tube of 8.5 mm in diameter and a wall thickness of 0.4 mm. This thin-walled tube was swelled in a 15% aqueous dimethylsulfoxide solution up to 12 mm in diameter, and then passed through the two-pass tube mentioned above. By washing dymethylsulfoxide in water, the outer hydrogel tube collapsed to its original diameter. Previously, however, the two-channel tube was modified so that both holes were sealed at one cone by gluing blocks of the same material soaked in dimethylsulfoxide and allowed to air dry partially. Then a hole of 1.5 mm diameter was drilled 20 mm from the blinded hole into the hole of smaller diameter and the two-channel tube was coated with silicone grease at a distance of 10 mm from both sides of the hole. The remainder of the tube was then coated with a 10% solution of partially hydrolyzed polyacrylonitrile with a swelling capacity of 70% water in dimethylformamide with the addition of 1% formaldehyde.

After transferring the thin-walled swollen tube and swelling it off as described above, the double-shell tube thus obtained was stored for 2 hours in 0.5% sulfuric acid, and then washed and dried to an almost hard state at + 50 ° C. As a result, the sheath is bonded firmly to the surface of the two-channel tube, except for places that have been primed with silicone grease. The blinded cone was then ground to a round, smooth end and two opposite holes were drilled into the larger diameter channel 5 mm from the end and their edges rounded.

The two openings were then temporarily plugged with rubber plugs and the catheter was immersed for 6 minutes in a mixture of 4 parts of concentrated sulfuric acid and 1 part of glycerin heated to 50 ° C. It was then rinsed in water, neutralized with aqueous sodium bicarbonate solution and washed again. At the opposite end, a 2.3 mm diameter hole was drilled into the narrow channel and a tube of partially hydrolyzed polyacrylonitrile of the type described in Example 1 was swollen with a solution of the same hydrogel in dimethylsulfoxide, swelling capacity of 50% water, 1.5 mm, wall thickness 0 4 mm and 50 mm length. This tube was then passed through a 2 mm and 100 mm long silicone rubber tube up to the point of insertion into the catheter.

In another operaol, a 8 mm thick silicone rubber tube, a wall thickness of 0.8 mm and a length of 300 mm was spirally cut along the entire length and then wound onto a hydrogel swollen catheter, a polyamide horsehair inserted into a spiral section and sealed with a two-component self-curing silicone rubber compound. Ethylene oxide was then blown through the interior of the catheter for 1 hour, after which the protruding outer tube of silicone rubber was sealed with a self-solidifying silicone rubber sealant, filled with a 0.01% aqueous Rivanol solution (i.e. acridine dye and antiseptic properties).

197 409 second cone of the outer tube, with one cone of polyamide horsehair enclosing the spiral cut glued into the plug thus formed · This created a removable catheter plug ·

The whole is shown in Fig. 3, where δ is the main passage (6), je 6 is the secondary channel leading to the balloon g. The base hydrogel tube z of the hydrogel with equilibrium swelling in water is 62%; , coated with a slippery, highly hydrophilized gel layer. The silicone rubber tubes 8 cover both the main tube 8 and the outer balloon inlet 11, made of a hydrogel of the same kind, but with a water swellability of 50%. The openings are covered with silicone sealant plugs. The tip of the coil £ 2 is rounded. A spiral notch 11 is formed in the tubing 11 with the interposed polyamide fiber 14 or horsehair, glued with silicone sealant, with the free end of the polyamide fiber, horsehair or string at the front. A second koneo 15 of this horsehair is glued into the rear plug 4 *. At 16, the polyamide horsehair is fastened by a piece of silicone sealant to the outer tube.

In the tubing, there are channels 17, 17 'connecting the passage g with the exterior, i.e. when used with the bladder cavity.

Prior to use, by pulling on the loose koneo fiber or horsehair 14, the outer tube 6 is removed from the silicone rubber of the required length, leaving the air exposed portions of the catheter to dry out at the other end and at the balloon lead 11. The exposed portion of the catheter is swollen, sterile, and ready to use, and insertion into the urethra is very easy and painless due to the highly hydrophilized topsheet having a low coefficient of friction in the swollen state.

Of course, the catheter may be filled with a solution of any suitable water-soluble drug prior to closing the outer tube. During storage, the drug diffuses into the hydrogel, from which it can then gradually diffuse during administration.

Parts and percentages in the examples are by weight unless otherwise indicated.

By rubber is meant a hydrophobic natural or synthetic elastomer, preferably cross-linked.

Claims (3)

SUBJECT OF THE INVENTION Hydrophilic tubular device for insertion into body cavities, formed from a hydrophilic gel or provided with a hydrophilic gel on its surface, which upon application comes into contact with the wall of the body cavity, characterized in that the tubular device is closed in a removable and sterile state in a removable a hydrophobic flexible package (3). Hydrophilic tubular device according to claim 1, characterized in that the hydrophobic resilient sheath (3) is made of rubber and provided with means for facilitating removal of the sheath at a selected location, for example by helical notches (13) or glued fiber (14). 3. A process for the production of a hydrophilic tubular composition as claimed in claim 1 or 2, characterized in that: 197 409 a hydrophobic flexible sleeve in the form of a rubber tube (3), the inner diameter of which is in the swollen state less than the outer diameter of the tubular product (1) swollen with water or saline, is swollen on the product with volatile or washable or wash until the hydrophobic resilient sheath collapses to its original diameter.