WO2007137731A2 - Utilisation d'un collagène à principes actifs ostéoinducteurs pour le traitement de lésions des ligaments et / ou des tendons - Google Patents

Utilisation d'un collagène à principes actifs ostéoinducteurs pour le traitement de lésions des ligaments et / ou des tendons Download PDF

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Publication number
WO2007137731A2
WO2007137731A2 PCT/EP2007/004513 EP2007004513W WO2007137731A2 WO 2007137731 A2 WO2007137731 A2 WO 2007137731A2 EP 2007004513 W EP2007004513 W EP 2007004513W WO 2007137731 A2 WO2007137731 A2 WO 2007137731A2
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WO
WIPO (PCT)
Prior art keywords
collagen
tendon
use according
ligament
defects
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PCT/EP2007/004513
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German (de)
English (en)
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WO2007137731A3 (fr
Inventor
Arne Briest
Original Assignee
Ossacur Ag
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Publication of WO2007137731A2 publication Critical patent/WO2007137731A2/fr
Publication of WO2007137731A3 publication Critical patent/WO2007137731A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments

Definitions

  • the invention relates to uses of a collagen of animal origin having osteoinductive agents.
  • Tendons and ligaments form the natural transitions between bone and bone and between bone and bone in human and animal bodies. They consist mainly of supporting and connective tissue and are responsible in particular for the flexibility or mobility of body joints or the bone skeleton.
  • tendons and ligaments are subject to constant mechanical stress.
  • the use of tendons and ligaments is under certain circumstances, especially in sports activities, additionally increased. This can lead to accelerated signs of wear and, in particular, to an increased susceptibility to injuries due to tendon or ligament damage.
  • the repair of tendon and ligament function is supplemented by the addition of bone growth factors in the area of the fixation site (Anderson K. et al., Augmentation of tendon healing in an intra-articular bone tunnel using a bone growth factor, Am. Sports, Med. 2001; 29: 689-98], [Rodeo SA et al., Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel, Am. Sports, Medicine 1999; 27: 476-88]. , [Cheng H et al., Osteogenic activity of the fourteen types of human morphogenetic protein (BMPs), J. Bone Surg., Am. 2003, 85: 1544-52]).
  • BMPs human morphogenetic protein
  • a product for fixing connective tissue to bone is known, for example, from WO 01/66130 A1.
  • the invention therefore has the object of providing an improved possibility for the treatment of tendon and / or ligament defects compared to the treatment methods known from the prior art.
  • Claim 20 relates to a suitable kit for the treatment of tendon and / or ligament defects. Preferred embodiments of the kit are the subject matter of claims 21 to 23. The wording of all claims is hereby incorporated by reference into the content of the description. According to the invention, a collagen of animal origin which has osteoinductive (osteogenic) active ingredients is used for the treatment of tendon and / or ligament defects (tendon and / or ligament damage).
  • COLLOSS ® and COLLOSS ® E are in each case to collagen of animal origin, each of which has osteoinductive agents wherein the collagen forms a lyophilized extract together with the osteoinductive agents.
  • osteoinductive agents wherein the collagen forms a lyophilized extract together with the osteoinductive agents.
  • osteoinductive agents are to be understood as meaning agents which induce and / or enhance bone growth (osteogenesis) both inside and outside the human and / or animal body.
  • chondroinductive agents are to be understood as meaning agents which induce and / or enhance cartilage growth (chondrogenesis) both inside and outside the human and / or animal body.
  • Refixation in the sense of the present invention should be understood as the restoration of the attachment of tendons or ligaments to the respective corresponding bone.
  • An implant in the sense of the present invention should generally be understood as meaning a material which is introduced permanently or temporarily into a human and / or animal body.
  • a medical-technical implant is to be understood as meaning an implant which assumes bodily functions after introduction into the human and / or animal body.
  • the bodily functions may, in particular, be functions of the bone tissue, for example as fastening material for tendons and / or ligaments.
  • the region to be treated between a defective tendon or the defect is to be understood as a defect region
  • the invention makes it possible, in particular, to stabilize and in particular to reinforce a refracted chord or a refixed band.
  • This is made possible with particular advantage by the osteoinductive properties of the collagen used according to the invention, which cause new formation of bone tissue in the defect region, preferably in the direction of the defective tendon and / or the defective ligament.
  • the collagen acts in particular as a stabilizing carrier component for the osteoinductive agents.
  • Collagen and the osteoinductive agents form an optimal reflection of the natural conditions in the bone tissue.
  • the osteoinductive properties in the defect region treated according to the invention in particular in the region of the refixation site, can unfold optimally. This allows successful treatment of tendon and / or ligament defects and preferably results in shortened postoperative treatment times.
  • the invention further relates to the use of a collagen of animal origin, which has osteoinductive agents, for the production of a shaped body, in particular in the manner of an implant, for the treatment of tendon and / or ligament defects.
  • the shaped body is implanted in the treatment of tendon and / or ligament defects between bone and tendon or between bone and ligament.
  • the shaped article may optionally contain further components, for example binders and salts.
  • the molding body crosslinked, preferably with chemical crosslinking agents.
  • the shaped body is preferably in the form of bars, rings or cylinders.
  • the shaped bodies it is possible for the shaped bodies to be present as cuboids, slices or the like.
  • the shaped body is present as a disk.
  • the shaped body is preferably convertible into a gel-like material by the addition of liquids, for example water or salt solutions, in particular a physiological saline solution.
  • liquids for example water or salt solutions, in particular a physiological saline solution.
  • the shaped bodies can be converted into a gel-like material by adding blood, in particular patient blood.
  • the reciprocal conversion of the shaped body into a gel-like material and vice versa makes it advantageously possible to adapt the dimensional stability of the shaped body. In this way, a targeted adaptation of the molding to the topology of the defect region to be treated is possible.
  • the invention also relates to a method of treating tendon and / or ligament defects wherein an effective amount of a collagen of animal origin having osteoinductive agents is employed or administered.
  • the treatment is initiated by the location of tendon and / or ligament defects.
  • the defects are localized by a reflection of the affected body regions.
  • tendon and / or ligament defects are located using an arthroscopic surgical technique.
  • the tendon and / or ligament function is performed by a restored arthroscopic surgery.
  • defect localization and restoration of tendon and / or ligament function are performed as part of the same arthroscopic procedure.
  • the tendon and / or ligament function may also be preferable to restore the tendon and / or ligament function as part of an open operation. Most preferably, the tendon and / or ligament functions are restored by refixation.
  • Refixation is preferable for complete tears and / or ligament tears.
  • a refixation can also be carried out in the case of tendon and / or ligament defects, whereby the defects are in particular deep cracks, which preferably make up more than half of the chord or ligament thickness.
  • the tendons and / or ligaments are completely excised and refixed to the bone.
  • the treatment is carried out with the aid of medical implants.
  • the medical implants may be formed from a resorbable or non-resorbable material.
  • the materials may in particular be metals, preferably titanium, tantalum or magnesium, or metal alloys.
  • the materials may be ceramics.
  • sutures are used in the method according to the invention.
  • holes are made in the bone tissue which is in the area of the defect region to be treated.
  • the sutures are attached to the defective tendon and / or on the defective band, in particular knotted. By attaching the sutures to the holes created in the bone, the connection between bone and tendon or restored between bone and ligament.
  • the collagen used according to the invention (collagen, which comprises the osteoinductive agents) is preferably implanted in the region of the applied holes. In this way, the restoration of the preferably original tendon and / or ligament function is supported, in particular accelerated.
  • a so-called bone resection in particular in the form of a groove or a channel, be made.
  • holes are pierced through the bone in the lateral boundaries of an applied bone gland, which are provided for receiving suture materials.
  • the bone channels and channels are preferably provided with the collagen used according to the invention (collagen with the osteoinductive agents).
  • the suture cords are particularly advantageously passed directly through the tendon or ligament and through the holes made in the bone and then contracted. In this way the connection between bone and tendon or between bone and ligament is restored. Due to the osteoinductive properties of the collagen used according to the invention, the tendons and / or ligaments fixed to the respective bone are additionally stabilized, in particular reinforced.
  • the bone is preferably "refreshed" in order to remove in particular soft parts, for example supporting and / or connective tissue, thus enabling a better fixation of the tendons and / or ligaments the tendon and / or ligament margins are refreshed prior to refixation to facilitate, in particular, the uptake of the sutures.
  • the treatment of tendon and / or ligament defects made with the help of suture anchors or screws are preferably implanted in applied bone channels in the area of the defect region to be treated.
  • the suture anchors or screws are provided in particular after their implantation with the collagen used according to the invention.
  • the collagen used according to the invention is implanted in the region of the implanted suture anchors or screws.
  • the fixation of the tendons and / or ligaments to the implanted suture anchor or screws advantageously takes place via sutures.
  • the collagen used according to the invention is particularly preferably located after fixation between bone and tendon or between bone and ligament.
  • the osteoinductive properties of the collagen used according to the invention result, in particular, in the regeneration of bone tissue, preferably in the direction of the attached tendon and / or the attached ligament.
  • the tendon and / or ligament defects are so-called ruptures, i. H. Cracks.
  • ruptures i. H. Cracks.
  • the ruptures depending on the size are divided into small ruptures or so-called mass ruptures.
  • the tendon and / or torn ligaments may in particular be longitudinal, transverse or irregular.
  • the tendon and / or ligament defects are located in the region of body joints, in particular in the area of the knee joint, ankle joint, wrist and / or shoulder joints, preferably in the region of shoulder joints.
  • the shoulder joint is the most flexible joint in humans. It is a ball joint whose articular surfaces are formed by the head of the humerus and the socket of the scapula. An intact shoulder joint is a prerequisite for mobility in several Bending planes and the axis of rotation of the arm. Due to persistent, in particular by heavy physical or sports activities, it comes frequently to wear and tear. The tendons and / or ligaments in the region of the shoulder joint are therefore particularly susceptible to defects, especially ruptures. Therefore, the human and / or animal shoulder joint is a particularly preferred indication, which is treatable with the aid of the invention.
  • the tendon defects are tendon defects of the rotator cuff.
  • the rotator cuff is responsible for the dynamic fixation of the humerus to the shoulder joint socket.
  • the rotator cuff is a muscle sheath made up of four different muscles: the supraspinatus muscle, the subscapularis muscle, the infrasulatus muscle, and the teres minor muscle.
  • the muscles of the rotator cuff have different areas of origin on the shoulder blade and move towards the humeral head. Near the humeral head, the muscles pass into their respective tendons, partially merging into a common tendon plate, which hugs the humeral head.
  • the permanent strain on the human and animal shoulder joint leads to a corresponding load on the rotator cuff.
  • This basically causes an increased potential susceptibility of the tendons and / or ligaments, in particular of the tendons, to the formation of defects, preferably in the form of cracks.
  • the tendon defects are a tendinous defect of the supraspinatus muscle (supraspinatus muscle, upper backbone muscle).
  • the tendon of the muscle supraspinatus is seen from a medical point of view figsten of defects, especially ruptures or cracks affected. This is due in particular to the fact that the tendon extends below the so-called shoulder roof.
  • the shoulder roof thus represents a kind of upper limit for the tendon of the supraspinatus muscle, on which the tendon can rub off during frequent exercise. This leads to an increased susceptibility to damage of the tendon, especially in the form of ruptures.
  • defects of the tendons and / or ligaments, particularly the tendons, of the shoulder joint are treated by a multi-step procedure.
  • the treatment is carried out in two steps.
  • the defects are localized. This is preferably done by a mirroring of the shoulder, which is carried out in particular by means of an arthroscopic technique.
  • the defect localization is carried out as part of a so-called Bursoskopie (reflection of the bursa of the shoulder joint).
  • Bursoskopie reflection of the bursa of the shoulder joint.
  • the bursoscopy allows in a particularly advantageous manner, a reflection or visualization of the shoulder roof bottom (Acromionunter Structure) and in particular the rotator cuff.
  • the localization of tendon and / or ligament defects in the region of the shoulder joint is possible.
  • a so-called subacromial decompression can be carried out.
  • soft tissue in particular parts of the bursa, is ablated on the shoulder-roof underside and preferably bone resections are performed.
  • the soft tissue removal is preferably carried out with the aid of so-called shavers, ie milling. With advantage bleeding, which occurs during the operation can stand, with electric knives deserted.
  • the bone resections are preferably performed to produce bone gullies or bone channels.
  • the restoration of the attachment between bone and tendon or between bone and ligament preferably in the form of a refixation.
  • the restoration of the attachment can be carried out in particular by means of an arthroscopic procedure. Defect localization and restoration of the tendon and / or ligament function are preferably carried out in the context of the same arthroscopic procedure.
  • the restoration of the attachment between the bone and the tendon or between the bone and the ligament takes place by an open surgical technique, preferably by an open fixation.
  • the bands are the ligaments of the knee joint, in particular the so-called cross and / or side bands.
  • the cruciate ligament is preferably the anterior cruciate ligament (ligamentum cruciatum anterius).
  • anterior cruciate ligament ligament cruciatum anterius.
  • front drawer phenomenon ie in a bent knee, the lower leg can be pushed from back to front.
  • the cruciate ligament is the posterior cruciate ligament (ligamentum cruciatum posterius) whose damage, in particular in the form of a tear, causes the so-called posterior drawer phenomenon (in the case of a bent knee, the lower leg can be pushed from the front to the back)
  • the lateral ligaments are preferably the inner ligament (medial collateral ligament) and / or the outer ligament (lateral collateral ligament).
  • the ligaments of the knee joint may be the patellar ligament (ligamentum patellae), which attaches directly to the so-called tibial tubercle directly below the knee joint.
  • the bands are the ligaments of the ankle, in particular the inner ligament (deltoid ligament) and / or the outer ligaments.
  • the outer bands are particularly preferred because they are particularly often affected by Umknickinen, especially in the form of cracks.
  • the outer ligaments are preferably the anterior talofibular ligament, the posterior talofibular ligament and the fibulocalcaneal ligament.
  • the ligaments of the ankle may be the anterior and / or posterior tibial-fibular ligaments (tibiofibular anterior ligament and / or tibiofibular ligament ligament) which hold the so-called ankle joint together.
  • the tendon and / or ligament defects are so-called acute defects.
  • the acute defects are defects which have arisen as a result of a traumatizing event, for example a sports accident.
  • the active ingredients are of native origin. This means that the active ingredients come from natural sources, in particular from tissues, preferably from bone tissue. Preferably, the active ingredients are in their native structure, d. H. in a structure that the active ingredients possess in their natural environment.
  • the collagen has active substances which induce the growth of supporting and / or connective tissue and in particular strengthen it.
  • This is particularly advantageous, since in this way a new formation of supporting and / or connective tissue is effected in this way by the collagen used according to the invention at the treated defect region, in particular at the refixation site, in addition to the new formation of bone tissue.
  • the formed supporting and / or connective tissue contributes with particular advantage to an additional stabilization, in particular reinforcement, of the restored connection between bone and tendon or between bone and ligament.
  • the collagen has chondroinductive agents.
  • the active ingredients are growth factors, preferably recruitment, adhesion, maturation and / or differentiation factors.
  • the recruiting factors are, in particular, chemotactics (chemotaxines), for example leukotrienes. These agents are eminently suitable for attracting cells to the defect region.
  • the recruited cells are, in particular, bone cells, fibroblasts, thrombocytes and / or their progenitor cells. Bone cells and fibroblasts are particularly preferred because they are responsible for the regeneration of bone, supporting and connective tissue in the area of the defect region. recruited progenitor cells mature, in particular under the influence of further growth factors, preferably differentiation factors, into finished cells.
  • the formation of new bone, supporting and connective tissue in the defect region brings about a stabilization of the treated defect region, in particular of the refixed tendons and / or ligaments, in a particularly advantageous manner.
  • the so-called adhesion factors are, in particular, cyctactin, tenascin, laminin and / or fibronectin.
  • the adhesion factors are preferably used to fix the recruited or immigrated cells in the defect region.
  • the active substances are preferably proteins and / or peptides, preferably extracellular proteins and / or peptides.
  • the active ingredients are cytokines, ie sugary (glycosylated) proteins and / or peptides.
  • the active ingredients are at least one substance from the group comprising BMP-1 (bone mineralized protein-1), BMP-2 (bone mineralized protein-2), IGF1 (insulin growth factor 1) , TGF ß1 (transforming growth factor ß1), FGF (fibroblast growth factor), VEGF (vascular endothelial growth factor) and PDGF (platelet derived growth factor).
  • BMP-1 bone mineralized protein-1
  • BMP-2 bone mineralized protein-2
  • IGF1 insulin growth factor 1
  • TGF ß1 transforming growth factor ß1
  • FGF fibroblast growth factor
  • VEGF vascular endothelial growth factor
  • PDGF platelet derived growth factor
  • the active ingredients are in the form of an active substance complex.
  • the active ingredient complex is a mixture of the active ingredients. This is particularly advantageous since the mixture preferably contains all the active ingredients necessary for the regeneration of a bone, cartilage, supporting and / or connective tissue. Furthermore, possibly occurring loss of activity of individual drugs due to at least partially overlapping effect spectra of other active ingredients present in the complex can be taken over.
  • COLLOSS Products ® and COLLOSS ® E have the active ingredients specified in this description, preferably as a complex of active ingredients on.
  • the collagen is type I 1 II, III or IV collagen.
  • the collagen is preferably type I collagen.
  • the collagen is particularly preferably tendon and / or ligament collagen , preferably around tendon collagen.
  • the collagen is at least partially, preferably completely, in its native structure. Native collagen is present in a triple-helical superstructure (triple-helical collagen fibrils), with the superstructure formed from single-helical collagen molecules or fibrils. This is particularly advantageous, since the active ingredients are present in this way in their natural carrier matrix. Thus, the active ingredients can develop their osteoinductive properties particularly well.
  • the collagen is at least partially, preferably completely, in a different structure from its native structure.
  • the majority of the collagen is in a structure different from the native structure and to a lesser extent in the native structure.
  • the proportion of collagen with a structure differing from the native structure is preferably at least 70 to 90%, in particular at least 80 to 90%, preferably at least approximately 90%, based on the total amount of the collagen used according to the invention.
  • the collagen has randomly arranged (random) collagen fibrils, preferably with a single hepatic structure.
  • the collagen fibrils are preferably assembled together to form a superordinate structure.
  • the collagen fibrils are preferably assembled into a net-like superstructure.
  • the collagen is bovine, porcine and / or equine origin.
  • the collagen is of equine origin.
  • the use of collagen from equine sources is due to a lower risk of transmission of pathogens particularly preferred. That available under the name COLLOSS ® product of the applicant has to collagen of bovine origin. That available under the name COLLOSS ® E product of the applicant has to collagen of equine origin.
  • the collagen is obtained by crushing and demineralizing animal bone, in particular bovine, porcine and / or equine bone, preferably equine bone.
  • the bone is preferably degreased after demineralization.
  • the degreasing is advantageously carried out with ketones, in particular acetone, and / or alcohols, in particular ethanol.
  • the collagen and the osteoinductive agents are isolated from the same biological materials.
  • the biological materials are in particular tissue.
  • the collagen and the active ingredients are isolated from the same biological material, in particular from the same bone tissue.
  • the collagen and the active ingredients can be provided simultaneously in a single isolation step.
  • the isolation step may also be repeated.
  • the collagen is present as an extract.
  • the collagen is present together with the active ingredients as a common extract.
  • the extract contains both the collagen and the osteoinductive agents.
  • the collagen and the active ingredients form a functional unit in this way.
  • the extract consists of the collagen and the active ingredients.
  • the extraction of the extract takes place in particular by extraction of the animal bone with a denaturing agent.
  • the extraction is carried out with guanidine and / or a guanidine salt, for example with guanidinium hydrochloride. This is particularly advantageous because in this way the hold active ingredients, in particular drugs with osteoinductive properties, can be extracted together with a part of the bone collagen.
  • the extracted extract preferably contains both the collagen and the active ingredients.
  • the extraction step may optionally be repeated several times. Therefore, enrichment of the active ingredients in the extract is possible with particular advantage.
  • the demineralized bone can be mixed with chelating agents prior to extraction for the complexation of ions, in particular of divalent ions, for example of magnesium and / or calcium ions.
  • the chelating agents are in particular EDTA (ethylene-diamine-tetra-acetate) and / or TRIS.
  • the collagen is renatured.
  • the collagen is renatured after denaturation with guanidine and / or a guanidine salt, for example guanidinium hydrochloride.
  • the osteoinductive agents are already contained in the collagen prior to renaturation.
  • the renaturation takes place in particular by removal of a denaturing agent, preferably in the form of a dialysis.
  • the collagen and, in particular, the active ingredients are each in functional form after renaturation.
  • the collagen preferably has a net-like superstructure.
  • the active ingredients are present in particular in their native structures.
  • the collagen serves as a suitable carrier matrix for the active ingredients, whereby the active ingredients can develop their properties optimally. With regard to further features of the active ingredients, reference is made to the previous description.
  • the collagen is preferably lyophilized together with the osteoinductive active ingredients.
  • lyophilization a shaping of the collagen is achieved with particular advantage.
  • the collagen with the osteoinductive active ingredients is produced or producible by
  • Demineralization with acid preferably hydrochloric acid
  • acid preferably hydrochloric acid
  • chelating agents in particular EDTA and / or TRIS
  • the collagen may have fillers.
  • the fillers are preferably calcium phosphates, in particular tricalcium phosphates and / or hydroxyapatite.
  • the collagen in commercially marketed by applicants under the name OSSAPLAST ® product.
  • OSSAPLAST ® is a granulated ß-tricalcium phosphate.
  • the modification of the collagen with fillers may be particularly preferred for increasing the osteoconductive (load-bearing) properties of the collagen and in particular for increasing the collagen surface.
  • the collagen has other active ingredients in addition to the osteoinductive agents.
  • the other active substances may in particular be antimicrobial substances, preferably antibiotics. In this way, inflammatory reactions in the area of tendon and / or ligament defects, in particular dere in the region of the Refixationsstelle be suppressed. This reduces the risk of developing chronic defects.
  • the other active ingredients may also be cytostatic and / or antibiotics. These agents are particularly preferred from a therapeutic point of view.
  • the collagen is porous.
  • the collagen has interconnecting pores.
  • the collagen preferably has pores with a diameter of at least 100 .mu.m, in particular from 100 to 300 .mu.m, preferably of about 200 .mu.m. This is particularly advantageous for the recruitment and ingrowth of cells and / or their progenitor cells into the bone tissue of the defect region, in particular the refixation site.
  • the collagen is cross-linked, preferably chemically cross-linked.
  • the collagen is in particular cross-linked with a carbodiimide, for example with N- (dimethylaminopropyl) -N-ethylcarbodiimide (EDC) 1 or with glutaraldehyde.
  • the collagen used according to the invention is in a gelatinous state.
  • the provision of the collagen according to the invention in the form of a gel allows, in particular, a simple and convenient application in the region of the defect region.
  • the collagen gel-forming components in particular polysaccharides on.
  • the polysaccharides are, in particular, at least one polysaccharide from the group comprising hyaluronic acid, heparin, cellulose and their derivatives.
  • the cellulose derivatives are preferably at least one derivative from the group comprising carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC) and ethylhydroxyethylcellulose (EHEC).
  • the collagen preferably has a so-called dispersant.
  • the dispersant is in particular aqueous liquids, in particular a physiological saline solution.
  • the dispersant is preferably blood, in particular patient blood, for example fresh blood.
  • the dispersant may be anticoagulated blood or a PRP (Platelet Rieh Plasma) fraction of blood.
  • PRP Platinum Rieh Plasma
  • the constituents and factors present in the blood or in a blood fraction, in particular platelets and preferably their released substances, may themselves have osteoinductive properties and in particular lead to increased formation of bone tissue in the defect region through interaction with the collagen and the osteoinductive agents.
  • the collagen and the osteoinductive agents are sterilized or are in sterilized form.
  • sterilization a variety of conventional sterilization methods come into consideration. Sterilization by radioactive irradiation is preferred, preferably by ⁇ -irradiation.
  • the collagen and the osteoinductive agents are sterilized with ethylene oxide.
  • the collagen and the active ingredients are aseptically treated and / or prepared.
  • the collagen and the osteoinductive agents may be aseptically treated and / or prepared by the use of sterile filtered antibiotic solutions, preferably a sterile filtered gentamycin solution.
  • the collagen used according to the invention is preferably present in packaged form, in particular in sterile packaged form.
  • the collagen can be stored for an extended period of time, in particular over a period of several months, without any impairment of the properties of the collagen.
  • lagens and in particular the osteoinductive agents comes.
  • Plastic materials are particularly suitable as packaging materials.
  • the packaging materials can be designed as syringes, in particular as single-chamber or two-chamber syringes.
  • the invention further relates to a kit, in particular for the treatment of tendon and / or ligament defects, comprising at least a first container and a second container, wherein the first container comprises an osteoinductive agents containing collagen of animal origin and the second container at least one medical implant.
  • the medical implants are suture anchors and / or sutures.
  • the sutures may in particular be resorbable or non-absorbable.
  • the above study involved 13 patients, 2 of whom suffered from a minor rupture, 5 patients from a moderate rupture, 3 patients from a large ruptured rotator cuff, and a further 3 patients from a massive rupture in the rotator cuff.
  • the healing process was reviewed 12 weeks after shoulder arthroscopy using magnetic resonance imaging (MRI). It was found that the treatment was particularly successful in 6 patients. Only 3 patients had to undergo another surgical procedure.
  • MRI magnetic resonance imaging

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Abstract

Utilisation de collagène d'origine animale, qui possède des principes actifs ostéoinducteurs, pour le traitement de lésions des ligaments et / ou des tendons, et kit associé.
PCT/EP2007/004513 2006-06-01 2007-05-22 Utilisation d'un collagène à principes actifs ostéoinducteurs pour le traitement de lésions des ligaments et / ou des tendons WO2007137731A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006026589A DE102006026589A1 (de) 2006-06-01 2006-06-01 Verwendung eines Kollagens mit osteoinduktiven Wirkstoffen zur Behandlung von Sehnen- und/oder Bänderdefekten
DE102006026589.0 2006-06-01

Publications (2)

Publication Number Publication Date
WO2007137731A2 true WO2007137731A2 (fr) 2007-12-06
WO2007137731A3 WO2007137731A3 (fr) 2008-10-16

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PCT/EP2007/004513 WO2007137731A2 (fr) 2006-06-01 2007-05-22 Utilisation d'un collagène à principes actifs ostéoinducteurs pour le traitement de lésions des ligaments et / ou des tendons

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DE (1) DE102006026589A1 (fr)
WO (1) WO2007137731A2 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001066130A1 (fr) * 2000-03-09 2001-09-13 Sulzer Biologics Inc. Produit et procede pour ancrer biologiquement du tissu conjonctif a un os
WO2003011107A2 (fr) * 2001-07-27 2003-02-13 The Brigham And Women's Hospital, Inc. Remplacement biologique d'un caillot de fibrine

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US3168584A (en) * 1963-01-17 1965-02-02 Shell Oil Co Manufacture of aromatic hydrocarbons
US6083522A (en) * 1997-01-09 2000-07-04 Neucoll, Inc. Devices for tissue repair and methods for preparation and use thereof
US6179872B1 (en) * 1998-03-17 2001-01-30 Tissue Engineering Biopolymer matt for use in tissue repair and reconstruction
CA2365376C (fr) * 2000-12-21 2006-03-28 Ethicon, Inc. Utilisation d'implants en mousse renforces ayant une meilleure integrite pour la reparation et la regeneration de tissus mous
WO2004004663A2 (fr) * 2002-07-09 2004-01-15 Stryker Corporation Compositions et methodes de permettant de stimuler la croissance ligamentaire et de reparer les ligaments
BR0317715A (pt) * 2002-12-27 2005-11-22 Angiotech Int Ag Composições e processos de uso de collajolie
CA2543255C (fr) * 2003-10-22 2014-08-12 Encelle, Inc. Methodes et compositions destinees a regenerer le tissu conjonctif
US8133500B2 (en) * 2003-12-04 2012-03-13 Kensey Nash Bvf Technology, Llc Compressed high density fibrous polymers suitable for implant

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001066130A1 (fr) * 2000-03-09 2001-09-13 Sulzer Biologics Inc. Produit et procede pour ancrer biologiquement du tissu conjonctif a un os
WO2003011107A2 (fr) * 2001-07-27 2003-02-13 The Brigham And Women's Hospital, Inc. Remplacement biologique d'un caillot de fibrine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RODEO S A ET AL: "USE OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 TO ENHANCE TENDON HEALING IN A BONE TUNNEL" AMERICAN JOURNAL OF SPORTS MEDICINE, WALTHAM, MA, Bd. 27, Nr. 4, 1. Januar 1999 (1999-01-01), Seiten 476-488, XP002940479 ISSN: 0363-5465 in der Anmeldung erwähnt *

Also Published As

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DE102006026589A1 (de) 2007-12-06
WO2007137731A3 (fr) 2008-10-16

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