DE3115763A1 - Medical depot probe for the local protracted release of active substance - Google Patents

Abstract

The depot probes according to the invention utilize the action principle of the so-called PMMA chain (polymethyl(meth)acrylate beads supplemented with gentamicin sulphate and firmly threaded onto wire) and are intended, in particular, for the long-term antibiotic treatment of inflammation foci, mainly those which cannot be treated by the chain. A solid or paste-like to liquid filling (9) supplemented with the intended active substance can be introduced into a narrow probe cavity (1) comprising a head and a coupleable (7) terminal section (6) of flexible materials or with rigid head elements (2, 3, 4) and elastic intermediate pieces (5, 7). Passage openings (8) in the probe wall which are optionally backed by a meshwork or a permeable membrane permit transfer of active substance from the filling (9) into the tissue to be supplied. Instead of the filled cavity design, the probe head can be designed as a porous solid body on the pores of which the active substance is deposited. For removal of secreted fluid from the treated area thicker depot probes have a central longitudinal channel and, if appropriate, transverse channels; auxiliary means (e.g. endoscope, puncture probe) can be inserted through the longitudinal channel. Depending on the indication, the depot probes are all flexible or all rigid, have a circular or tape-like cross-section and diameters of about 2 mm to almost the width of a finger. <IMAGE>

Description

Medical depot probe for locally protracted active substance

release.

The invention relates to a medical device loaded with an active substance or loadable probe as an active ingredient depot for the local, protracted release of active ingredients the active ingredient not to be administered orally or parenterally.

For long-term antibiotic treatment post-traumatic or post-operative infected bones and soft tissues at the site of infection have been so-called since about 1976 Gentamycin PMMA balls or ball chains are known; reference is made to e.g. the literature cited below 1) The balls, which have a diameter of 7 mm, consist of the polymer Nethylmethacrylat-Zethylacrylat-Copolymer (PMMA), in which evenly distributes an antibiotic that can be leached by the body fluids (Gentamycin) is embedded. The balls are made individually or as a bed of balls or on a relatively stiff stainless steel 1) special print from euromed, issue 2 (1977), "Osteomyelitis: Treatment with Balls and Chains"; K.-H.Müller, I. Schneider, Therapy Week 27 (1977), 8528 ff., "Infections after osteosynthesis on the hip and pelvis and their therapy; same, ibid., 8544 ff., "Septic complications after osteosynthesis on the thigh "; W. Winterfeld, Medizinisch-Orthopädische Technik 98 (1978), 24 ff "Gent aniycin-l-'MMA-Ke tten: The alternative in the treatment of chronic Osteomyelitis "; G.Asche, K. Klemm, Current Traumatology 8 (1978), 387 ff.," Frahintervention in infected osteosynthesis using gentamycin PMMA ball chains "; J.Poigenfürst, V. Vécsei, Arch.Orthop.Traumat.Surg. 93 (1979), 273 ff., "Das creeping postoperative hip joint empyema; K. Klemm, Surgery of the Present, Volume IVa (1979), Treatment of abscessed bone and soft tissue infectionsU; G. Kollias, Therapy Week 30 (1980), 2456 ff., "Gentamycin PMMA chain ~ for local treatment after urological OperWiqn ".

Strand of polyfilament surgical wire immovable at a distance from one another 30 or 60 pieces lined up to form a chain. For bringing in the Balls or the cord (s), surgical debridement is always required. Apart from the revision of the infected area, which is necessary anyway In any case, the positioning of the chain is a relatively long or wide one Cut, as they are more or less one-way or the other. must be created and at least at the soft tissue treatment not by advancing in its longitudinal direction into the active position can be brought. When inserting the chain, its removal must already be taken into account will. If no later operational measures are planned - in such a case single balls would also be applicable - the chain is stretched in the direction of pull or meandering arranged, with the last ball protruding above the skin level after the primary wound closure. If removed in good time, the chain can attach to this prominent ball in the Usually pulled non-surgically. Is - with a bactericidal effectiveness of up to 80 days - the embedding time (in the bone focus) longer than 10 to 14 Days, the plastic balls are encapsulated by connective tissue. The removal of the Bullets that are encased in this way are difficult and may only be operational possible.

With all the advantages of the localized high concentration of active ingredients the areas of indication for the chain are limited and essentially exhausted on the infections identified in the literature cited.

Not known in the field is the non-surgical or only small surgical one local antibiotic treatment of foci of infection or infected organs inside the body by means of solid-body active ingredient depots that are easy to extract again. For example it is not possible to use a chain to identify hollow organs or cavities, e.g. stomach, forehead and maxillary sinuses, kidney, beber, lung and brain abscess cavities, or waveguides, e.g. treat urinary and fallopian tubes bactericidal or bacteriostatic. The reasons for the cancellation lie on the one hand in the necessary major surgical intervention in the organ, the Vessel or the conductor, on the other hand in the unavoidable interruption of the liquid-carrying Pathways, e.g. urinary and biliary tract, and finally in the considerable form resistance, which the ball chain offers, by about the walls of the treated conductor or Bulge organs into the chain gaps and tear when the chain is extracted, but would at least be injured.

The invention arises from the desire to develop local treatment options to improve inflammation and foci of pus in the organism.

The primary object of the invention is the application or The chain's operating principle - not for the active ingredient or its carrier material Gentamycin or PMElA are absolutely essential - also for the renovation to make use of such foci of inflammation, either with the chain not treated or which are difficult to access from a surgical point of view and with the previous local, parenteral, oral and other treatment options cannot be treated well enough.

Another task is seen in it, instead of the chain, an im With regard to the easy extraction, geometrically more favorable designed carrier for to provide the active ingredient.

The task is solved based on the procedures by means of Probes or catheters, possibly also drains, to penetrate the inside of the body and to supply this. According to the invention, the agent containing the active ingredient can be used for this purpose and releasing carrier material placed in a tubular elastic jacket be that has a good lubricity, and that for the access of body fluids is provided with openings to the carrier material; there is another possibility to classify the active substance in a e.g. rod-shaped solid body, its material can be penetrated by the body fluids. Such tubular or rod-shaped Structures according to the invention are furthermore as a depot probe or as a probe body designated; the Hogliffe do not require the depot probe with the active ingredient is already loaded. Unless otherwise noted, the following apply Explanations first of all, tube-type depot probes.

The depot probe essentially consists of the probe head and the Probe end part. In the simplest case, the head is a tubular hollow body Breakthroughs in the wall. The end part, like the head, can be a hollow body, however be designed without openings in the wall, or as a solid body. For the depot probe a one-piece or multi-piece design is possible. For the sake of both manufacturing the probe uls also the filling of the end head with the one containing the active substance Carrier material, it is cheaper to manufacture the head and end part separately and these to unite with each other only after the head has been filled.

This also has the advantage of reducing the length of the end part by cutting it off to be able to measure individually from a larger storage unit. The head can completely filled or manufactured so that it can only be filled for use. In any case The moldings of the carrier material must be dimensioned in such a way that they do not penetrate the passage openings for the body fluid in the wall of the head emerge can. Since, however, the drug concentration level around the probe used around, among other things, from the total surface of the carrier bodies, i.e. from their Depending on the dimensions, it will occasionally be advantageous instead of larger and e.g. spherical structures for the carrier material to be used as granules. In such cases, granules can escape from larger wall openings. 1 by preventing the granules from being placed in a fine-meshed sack made of synthetic fiber or metal wire mesh is included; A corresponding retention net or meshwork can also be provided or inserted on the inside of the head will.

The conventional ball chain is not along its metal wire axis resilient to pressure or thrust without losing their elongated shape. When advancing through a narrow passage it would snap or bend and its intended Make placement impossible. However, elongated rigid guide devices are to the Pulling the chain, e.g. into a shin sinus, is known. The delivery of the active ingredient however, by pushing their carrier forward without the aid of guide devices, this is part of the task the invention. Accordingly, the material or materials for the depot probe, or, in other words, the probe body, on the one hand, is sufficiently rigid and rigid, but on the other hand be sufficiently pliable and flexible for the probe to be can also be advanced on a curved narrow path. Furthermore, the outside must the probe or probe body should be as smooth and slippery as possible. Among other Materials known in the field of probes, catheters and drains include soft PVC a suitable jacket or wall material for the spot probes according to the invention. To increase the pipe stiffness of the head, the end section or both, the Pipe wall, provided it is made of a comparatively soft material, a stiffening one Insert (support structure), which can also be a spiral, be incorporated. Possibly the head of the probe can also be made of non-flexible material, e.g. metal, hard plastic, Glass, be made to allow a better advance. The same materials are also suitable for the end part of the probe; provided that, due to their design, the provide the necessary flexibility in the case of rigid materials for the probe body the sun head and / or the probe end part divided into several (rigid) segments which are coupled to one another via flexible connectors.

if glass can be used, the head can be made of porous glass produce in the pores of which the active ingredient can be deposited in vitro, to then likewise protractedly released by the body fluids in vivo to become. This compact design of the head is one of the possible realizations of the solid body mentioned above as the probe head; in the application of Rigid foaming is another such option. After covering such porous solid body with a perforated foil is the sliding ability of the probe head significantly increased. Porous glasses or hard or soft foams loaded with active ingredient or the like. can also serve as filling material for depot probes of the tube type.

The sliding ability of the depot probes when inserting them into anatomically pre-formed ones Channels can be particularly promoted by the fact that the probe head, at least its anterior region, with a coat of pasty mass that melts at body temperature and is easily detached, enveloped; suitable sliding materials are e.g. cocoa butter or masses in general, such as those used for suppositories.

As Teflon mentioned, the depot probe can be made up of one or more parts Design are manufactured. If the probe body is made up of several parts, its functional ones Parts,, probe head and probe end part, or e.g. in the case of a multi-part head, its Segments to be connected to one another to form the depot probe or the probe body that these do not separate from one another, especially when the probe is extracted. There are a number of possibilities for connecting the parts. On condition the same cross-sectional shape of the parts to be connected, hose-hose or pipe-pipe or hose-Lohr ends, e.g. by gluing the end faces quickly and securely connect with each other; pulling the ends over a joint Pin or core to a press fit, which can be glued at the same time, fulfills the same Purpose. Rod-hose or rod-tube ends can also, provided the diameter of the rod end is adapted to the inner diameter of the pipe end, in plug-in connection be joined together; the same applies to pipe-hose ends. Rod-rod ends are also advantageously to be connected to one another by gluing. With thermoplastics Instead of gluing, welding is an option. Otherwise, the Connection technology according to the material or the intended use of the depot probe; with appropriately hard materials, screw connections can also be used, for example or bayonet locks and the like. Around rigid parts or segments Nevertheless, to be added to a flexible depot probe, these become elastic Intermediate pieces coupled together.

In a further development of the invention, the depot probe has a central one Longitudinal channel on, possibly also side channels, which from the Periphery the probe open into the central channel. The depot probe then also combines the function an outlet, suction rinsing or pressure relief with a suitable diameter a longitudinal channel at the same time the possibility of auxiliary equipment such as optical fiber optics, Puncture probes to introduce thermocautery to the treatment site in the body. As a continuous drain designed and allowed with liquid-impermeable material of the longitudinal channel the depot probe basically also the treatment of fluid-carrying vessels or Head by placing the probe tightly to deliver its active ingredient directly to the tissue is able to prevent the flow of liquid and the active substance from the flow of liquid is neither diluted nor washed out.

Although the concept for the depot probes according to the invention with regard to the carrier for the active ingredient initially on solid materials of the type des y lA, the depot probe offers due to its comparatively stiff body with passage openings for the transfer of active substances just as well the possibility of the Active ingredient from pastes or liquids through permeable membranes protahed to transfer into the body.

The invention will now be explained in more detail with reference to figures. 1 shows the perspective illustration of an embodiment of the depot probe according to the invention; here with three filled head segments of different shapes the passage openings of the probe wall, FIG. 2 shows the top view of the two front ones Head segments of the probe according to iig. 1 in the unfilled state, FIG. 3 shows the cross section by the unfilled probe according to FIGS. 1 and 2 along line A-A in FIG. 2, FIG. 4 the top view of the central longitudinal section of a depot probe according to lig. 2, however with a central longitudinal channel and with side channels and FIG. 5 shows the cross section through a probe according to FIG. 4 along line B-B in FIG. 4.

In Fig. 1, several design variants for depot probes are according to presented the invention.

The depot probe 1 has a multi-part head, here with three segments 2, 5 and 4, which are connected to one another via elastic intermediate pieces 5. The probe end part 6 adjoins the head. here the connection of the head segment 4 with the 6 an intermediate piece 7 with a bayonet lock is selected here. The segments are hollow bodies with a circular cross-section (see. Fig. 3) and different shaped passage openings 8 for the contact of body fluid with the active ingredient-containing carrier material 9. Segment 4 also has a lattice structure indicated on the probe wall. Depending on the type of material - all are physiologically suitable compatible active ingredient fe - the walls of the segments are rigid or elastic. at rigid wall material, the elastic spacers, if desired 5 for a certain flexibility of the probe head. In the case of elastic wall material, if a flexible probe head is provided, a subdivision of the probe head in segments not required, but can be made up of unit segments as required Put together probe heads of different lengths; this is of course true also for rigid probe heads or probe heads made of rigid material of the segment walls. Inelastic connecting pieces can be used for elastic segment walls come. The end part 6 can be a solid or a hollow body, depending on requirements elastic (as symbolized in FIG. 1) or rigid and optionally extendable is. According to the materials and the overall design of the depot probe are for the connection between a segment or the end part and an intermediate piece adhesive, Screw, plug, bayonet and other unintentionally non-loosening connections possible. The segments can be linked to one another using these connection techniques or the probe head and the probe end part directly with one another without intermediate pieces associate.

The probe head. @ or its segments are with an active ingredient-containing Carrier material 9 charged. Is this in the form of a bed of, for example, spherical or granular particles, the particles are allowed to pass through the openings 8 of the probe wall for the active substance transfer cannot escape. To prevent The size of the particles should be chosen to be larger than the passage openings 8 (or the openings 8 smaller than the particles); finely divided granules can pass through a fine-meshed network into which the granulate is sunk, or which is inserted as a sleeve in the probe head, are retained; As materials all physiologically compatible materials can be used for depot probe bodies, especially soft or llart-P \ tC, plexiglass, glass, metals. Depending on the outside Probe diameter and the type of material and the required flexibility or static The strength of the probe head will be its wall thickness greater or lesser and a corresponding distance between the substrate and that of the applied Probe tissue adjacent to the body that makes contact with the active ingredient-containing carrier material could complicate with the tissue. With passage openings tapering from the inside to the outside however, the distance can be reduced in that the filling material e.g.

can be positioned in front of the openings in the manner of a ball or cone valve.

In Fig. 1, however, a continuously smooth outer wall is shown, corresponding to a gap-free filling of the openings 8 of the probe head with the active ingredient-containing carrier material 9. This can also be achieved. Carrier materials Like PMMA, they are solid polymers made from liquid or plastic mixtures (in which the active ingredient is introduced by adding it to the plastic mixture has been).

One now fills a probe head or the segments of a probe head including the passage openings completely with a @polymerizing plastic mixture and allows this to solidify, arrives; one to a filled one Probe head as shown in FIG. 1.

With this method, elastic probe heads can be used throughout cannot be produced. On the other hand, you can increase the size of the exchange Surface of the carrier material, the openings in the probe wall are much larger designed than with depot probes, which with individual particles of the Carrier material should be filled because of the static strength of the probe body lower than such because of the load-bearing properties of the block of carrier material static requirements are made.

Fig. 2 shows the top view of the front part of the head of the probe 1 according to Fig. 1, with both figures four equidistant for purely graphic reasons have longitudinal rows of passage openings 8; any other statically justifiable Arrangement of any shaped passage openings is possible. The empty probe body can either with a shadow of bodies of the active ingredient-containing carrier material filled or with a polymerizing, hardening, active ingredient-containing mixture be filled in to obtain a ready-to-use depot probe according to the invention. For the use of carrier materials in granulate form, this can be done by a dem Probe body on the inside adjoining network at the exit from the passage openings be prevented; for the application of a plastic or liquid carrier for the active ingredient would be to use a permeable membrane instead of a network.

3 shows a cross section through an unfilled depot probe according to FIGS. 1 and 2, namely according to line A-A in FIG.

The passage openings 8 of the probe wall 10 point on the longitudinal axis of the segment 2 vertical boundary walls -11. Such openings can taper from the inside to the outside due to material-removing machining Openings are widened, e.g. to allow spherical solid support materials, iti to be located in front of the passage openings further towards the periphery of the probe and improve contact with the tissue.

In FIG. 4, the central longitudinal section is through a probe body the invention shown with a central longitudinal channel 12 and transverse channels 13; in the @ rest the probe head corresponds to the probe according to Fig. 1 and 2 respectively.

As a result of the channels 12, 13, the depot probe used fulfills Zu- @ equal to the function of a drain. If the dimensions are sufficient, the longitudinal channel 12 the introduction of an auxiliary device in the area in front of the forehead of the probe head. For structural reasons, the arrangement of side channels in intermediate pieces 5 particularly advantageous; However, there is also the option of side channels E.g. through a passage opening to flow into the longitudinal channel.

FIG. 5 finally shows the probe according to FIG. 4 in cross section according to FIG Line B-B in Fig. 4.

The embodiments described in more detail in FIGS. 1 to 5 of depot probes according to the invention represent only a selection of the invention should explain in more detail. Depending on the indication, the Depot probes have a diameter of about a finger thickness down to 2 mm; both the length of the head and that of the end part of the depot probe are dependent on Needs to be measured.

For special applications, one should think about the supply Meningitis or from cerebral abscess cavities, it may be more advantageous if the depot probes have a flat oval to ribbon-shaped cross-section instead of a circular one. Otherwise, the introductory brief introduction to the medical Possibilities for using the depot probe at this point except for the lfinwcis, that the depot probe at the same time as a rail for the end-to-end cleaning after expired Inflammation of excised stenoses (for example in the fallopian tube) is not applicable be expanded. Finally it should be noted that depot probe bodies are made of non-radiopaque wateril alien with radiopaque elements or compounds can be enriched to the location of the applied depot; -sonde to be able to determine externally.

Because of the smooth outer material of the probe body (e.g. non-porous Plastic) and its uniform cross-section are the depot probes according to Invention encased less quickly and firmly than the conventional chain; the Embedding time can thus be expanded.

In a further development of the invention, there is the probe head the depot probe does not consist of one unit, but of a majority of narrow head parts, which are arranged in tufts as a common base at the end of the probe end part. Each head part with the probe end part can either directly or via each one possibly an elastic hissing piece or a common intermediate piece be connected.

With this configuration, the probe head can be fanned out achieve. This is advantageous for supplying larger spaces, e.g. the abdomen, small pelvis, pleural space or the like.

or large abscess cavities, since on the one hand the active substance-releasing surface enlarged and, on the other hand, above all those caused by the tuft-like broadening Probe head reachable contact area of the area to be supplied enlarged is.

Depot probes with invariably tuft-like probe head must, like also a chain to be inserted; however, the extraction is because of the total more uniform spatial shape of the head is more uncomplicated than with a chain; further A depot probe 1 with a table-like head also provides a guarantee for a longer time possible embedding time than when using a chain.

However, it is then also easily possible to use a depot probe with a tuft-like Head to its place of action by pushing forward, if the head parts first are arranged in the probe end part and then pushed out of this. this can be achieved by arranging the head parts e.g. on a common support plate, which can be moved in a hollow body probe end part by means of a guide rod. Using the guide rod, the head parts can be opened to facilitate the extraction retracted into the probe end part.

L e r s e i t e

Claims (19)

Claims 1 Med zinisch.e device for temporary arrangement within of the body as an active ingredient depot for the local and protracted body fluid effective release of the active ingredient held in or on a carrier material, characterized in that the device comprises a probe with a probe head and a probe end part is and the head is provided for storing the active ingredient. 2) depot probe according to claim 1, characterized in that the probe head is divided into segments. 3) depot probe according to claim 1 or 2, characterized in that the probe head or the segment is a hollow body for receiving the carrier material for the active substance and through openings (wall passages) for the passage of Body fluid or for the active ingredient to @ @ ffiibe. 4) depot probe according to claim 3, characterized in that the passage openings with reference to solid molded bodies contained in it of the carrier material for the active substance are dimensioned so that the shaped bodies do not penetrate the openings can. 5) depot probe according to claim 4, characterized by the outside inwardly widening passage openings. 6) Del) otsonde according to claim 3 or 4, characterized by one of the Inside the wall of the probe head or segment adjacent or insertable mesh or meshwork. 7) depot probe according to claim 3 or 4, characterized in that the passage openings with a plastically introduced and cured carrier material are completely filled out for the active substance. 8) depot probe according to claim 3 or 4, characterized in that in pasty to liquid carrier materials for the active ingredient in the area of the passage openings a permeable membrane seal is provided. 9) depot probe according to claim 1 or 2, characterized in that the probe head or the segment is a hollow or solid body with pores for the active substance is. 10) depot probe according to claim 9, characterized in that the probe head with a film with passages made of a film material that increases the lubricity is covered. 11) depot probe according to one of claims 1 to 10, characterized in that that between adjacent segments of the probe head and / or between the probe head and an intermediate piece is arranged in the probe end part. 12) depot probe according to one of claims 1 to 11, characterized in that that their components can be connected to one another in a tensile manner. 13) Depot probe according to one of claims 1 to 12, characterized in that that all of its components are flexible. 14) Depot probe according to one of claims 1 to 12, characterized in, that some of their components are flexible. 15) Depot probe according to one of claims 1 to 14, characterized in that that it has a continuous longitudinal channel. 16) depot probe according to claim 15, characterized by on the longitudinal channel connected cross channels. 17) Depot probe according to one of claims 1 to 16, characterized by a coating that melts away at body temperature or dissolves in the body. 18) Depot probe according to one of claims 1 to 17, characterized in that that the probe head consists of several head parts arranged like a tabletop on the probe end part is formed. 19) Depot probe according to claim 18, characterized in that the head parts out of the probe end part and each can be moved into it.