DE102009050252A1 - Medical biological implant of animal origin - Google Patents

Abstract

The present invention relates to a medical implant (10) comprising skin of a swimming or crawling locust paw or a portion of this skin containing subepithelial collagen.

Description

Field of the invention

The The invention relates to a medical biological implant animal Origin, determined in particular for the valve replacement is.

Technical background

It currently come in the context of the therapeutic replacement of defective tissue An individual has several strategies to apply. schematically It is possible, on the one hand, to use non-biological Implants and on the other hand the use of biological implants to distinguish which may be homologous if they from an individual of the same species as the one to be treated Individual origin, or heterologous, if the donor individual and are the recipient individual of different species. At present, however, none of these solutions is completely satisfactory.

in the special context of the replacement of defective heart valves in humans encounters the use of non-biological implants Often on thrombotic problems resulting from a reaction of the organism result in the implant, which is generally a long-term Anticoagulation of the recipient individual is required. Advantageously, biological implants generally show no thrombogenic effects. What the homologous valve implants in humans As far as their life is concerned, they are satisfactory sometimes subject to rejection reactions. The low Number of organ donors, however, limits their availability. This problem of availability arises naturally not with the heterologous implants. So only two form Materials the essential part of the heterologous valve implants, the pericardial bovine tissue on the one hand and the pig tissue, Aortic valve, on the other hand. These implants are generally non-thrombogenic, However, they have a shorter lifespan than the homologous biological Implants on, in particular due to a medium or long term progressive calcification of the implant.

In an attempt to solve the problem posed by the relatively short life of the heterologous implants, the patent proposes US Pat. No. 6,165,216 the use of semilunar valves (aortic or pulmonary valves) derived from other animal species, marine mammals. However, the relatively large thickness of these flaps, which would allow for greater resistance, also limits their flexibility. Furthermore, the efficacy of such implants has not yet been clinically tested, so the question of whether materials other than bovine or porcine could serve as useful replacement materials remains in abeyance.

Summary of the invention

So Now, the present inventors have unexpectedly demonstrated that the eel skin for the production of medical implants, like valves, vascular patches or ligaments is particularly suitable. Advantageously, implants combine on the basis of eel skin a longer life and a high flexibility.

Without To be bound by a particular theory are the inventors consider that the peculiarities of the eel skin that they are for make the production of medical implants suitable, in particular derive from the structure of the subepidermal collagen layer, which allows the skin of these animals, like an external tendon to act. This property is in particular - in different Degrees - to be found in pangolins, especially those who are swimming or crawling.

So the present invention relates to a medical implant, the skin of a panguin moving in a floating or crawling manner or part of this skin containing subepithelial collagen, includes, in particular for its or its use in the Replacement of defective tissue.

• – das Implantat ist für den Ersatz von Geweben bestimmt, die wiederholten mechanischen Belastungen ausgesetzt sind,
• – es ist aus der Gruppe bestehend aus einer Herzklappe, einem Gefäßpatch und einem Band ausgewählt,
• – es bildet eine Herzklappe, die einen Klappenhalter, welcher dazu bestimmt ist, an einer Wand eines Blutzirkulationskanals befestigt zu werden, sowie ein von dem Halter getragenes Verschlussorgan umfasst, wobei das Verschlussorgan auf der Basis der genannten Haut ausgebildet ist,
• – der Klappenhalter umfasst eine röhrenförmige Endoprothese,
• – das Tier ist aus der Gruppe bestehend aus Reptilien und Fischen ausgewählt,
• – das Tier ist ein Aal,
• – das Implantat wurde einer Behandlung mit einem vernetzenden Fixiermittel unterzogen,
• – das vernetzende Fixiermittel ist aus der Gruppe bestehend aus Glutaraldehyd, einem Agens auf Epoxidbasis, Formaldehyd, oder deren Mischungen ausgewählt, und
• – die Fettschicht sowie die tiefe Kollagenschicht sind bei dem Hautteil nicht vorhanden.

The implant according to the invention may have one or more of the following features, taken alone or in any (any) technically possible combination (s):

• - the implant is intended for replacement of tissues subject to repeated mechanical stress,
• It is selected from the group consisting of a heart valve, a vascular patch and a ligament,
• It forms a heart valve which comprises a flap holder which is intended to be attached to a wall of a blood circulation channel and a closure member carried by the holder, the closure element being formed on the base of said skin,
• The flap holder comprises a tubular endoprosthesis,
• - the animal is selected from the group consisting of reptiles and fish,
• - the animal is an eel
• The implant has been treated with a crosslinking fixative,
• - The crosslinking fixing agent is selected from the group consisting of glutaraldehyde, an epoxy-based agent, formaldehyde, or their Mischun selected, and
• - The fat layer and the deep collagen layer are not present in the skin part.

The The present invention also relates to the use of skin of one swimming or crawling locusting or crawling animal a subepithelial collagen-containing part of this skin for the production of a medical implant, in particular for the replacement of defective tissue in an individual is determined.

The The present invention also relates to a method of treatment of an individual having a defective tissue by replacement the defective tissue by an inventive medical Implant.

Description of the figures

1 is a photomicrograph of a cross-section of an eel skin. From the outside to the inside of the animal, one can see the epithelium in which scales are embedded, a subepithelial collagen layer, a fatty layer, and then a deep collagen layer.

2 Figure 3 is a perspective view of a three-quarter face of a first example of an implant according to the invention forming a replacement heart valve;

3 shows a plan view of the flap of 2 .

4 shows a view of a second example of an implant according to the invention, which forms an Endoklappe, and

5 is a plan view of a third implant according to the invention, which forms a vessel patch.

Detailed description the invention

As understood here, the term "pangolins" refers to the Animals whose skin dandruff, that is from the dermis protruding has rigid platelets With the expression "floating or crawling "is said to mean any kind of locomotion where some of the energy that is needed to do that Moving animals, from the muscles to the locomotives or limb, not just over the skeleton, but also about the skin, the - related on the inner vision, which connect the muscles with the skeleton - like an external tendon acts. This expression concludes An ongoing locomotion is not enough, either with the swim or creep, or in activity phases of the animal, which may differ from the swimming or crawling phases as in the case of amphibians.

Preferably are the invention floating or crawling locusts pangolins reptiles, fish. Prefers are eels, in particular eels of the genus Anguilla, like anguilla anguilla, anguilla rostrata.

As understood herein, the skin of the flapping or crawling locomotives, from the outside to the inside of the animal, has at least: (i) an epithelial layer 2 , (ii) a first collagen layer 3 , so-called subepithelial collagen layer, (iii) a fat layer 4 and (iv) a second collagen layer 5 , called deep collagen layer. The structure of the eel skin is exemplary in 1 shown, which is a five-fold magnification and the color has been performed with Sirius red.

The Preparing the skin for the preparation of a implant according to the invention can be carried out as follows become.

After this the eel was killed, his head is fixed on a hook. With the help of a scalpel becomes in the area of the neck of the eel one completed a circular skin incision.

Subsequently the skin is eviscerated and to the tail of the animal exposed. The on a support with a suitable diameter attached skin may then be incorporated into a fixative-containing bath be immersed.

in the Generally, the subepithelial collagen layer of the invention at least, floating or creeping moving pangolins a layer of substantially parallel collagen fibers. The subepithelial collagen layer may in particular at least 10, more particularly at least 20 one above the other lying layers consist of substantially parallel collagen fibers. The collagen fibers in the layers may have an orientation assume that an angle in particular between 30 and 60 °, continues in particular between 40 and 50 ° relative to the Has longitudinal axis of the animal. In particular, you can two successive layers with two different angles opposite relative values and similar absolute values exhibit.

The subepithelial collagen layer is largely responsible for the life and flexibility characteristics of the inventive medical implant; even if the medical implant according to the invention comprises only a part of the skin, this part contains the complete subepithelial collagen layer or a part thereof.

at a preferred embodiment of the invention medical implant, this has no fat layer and no deep collagen layer on.

The Epithelium is generally preserved. If necessary it can be removed by mechanical removal. The fat layer is significantly reduced by a silylation treatment simultaneously has a lipid extraction action by tetrahydrofuran. The removal the inner layers (deep collagen layer and fat layer) can also by mechanical removal, after the silylation treatment, or by slicing.

at a further preferred embodiment of the invention is the medical implant with a cross-linking fixative, such as glutaraldehyde or an epoxide-based agent such as formaldehyde or triglycidylamine, or another agent.

Of the Use of the crosslinking fixative is, in particular, that the implants before the rejection or the Calcification be protected.

Preferably the skin is in glutaraldehyde for at least 2 months with a concentration of 0.1 to 1 mass%, in particular fixed at 0.625 mass%, the fixing solution during the first 10 days every other day and over 2 Renewed once a week. After two months fixation the eel skin is treated by silylation.

In In one variant, no treatment against calcification is carried out.

Sterilization may consist in the immersion and storage of the eel lining in a glutaraldehyde solution. This treatment is for example in the French Application No. 07 55890 the applicant or in the European Application No. 08 104 444 described.

Preferably is the medical implant according to the invention intended for the replacement of tissues, the repeated mechanical Strains are exposed, such as the heart valves, the walls of blood vessels or the ligaments.

Out This reason is the medical invention Implant in particular a heart valve. The surgical procedure for implanting the invention medical device have no special changes the method of the prior art and can consequently easily performed by the skilled person.

The 2 and 3 show by way of example a first implant according to the invention 10 , which is intended to form a replacement heart valve. This implant 10 includes a flap holder 12 which is intended to be fixed in a blood circulation channel of a human, and a closure member 14 which is formed on the basis of the skin of a floating or crawling locomotive animal as described above.

In a known manner, the holder comprises 12 a flexible ring 16 with the axis A-A ', which is intended to be fixed in a wall of a blood circulation channel, for example, to the seat of a native heart valve, and three longitudinal ribs 18 on the circumference of the ring 16 are distributed angularly. Ribs 18 project substantially parallel to the axis AA '.

The ring 16 and the ribs 18 in limit a passage 19 for the blood circulation, in which the closing organ 14 is arranged.

The closing organ 14 is on the basis of a skin film, as defined above, formed. It has a substantially tubular overall shape with the axis AA '. It includes a cylindrical base 20 passing along an inner circumference of the ring 16 is tightly fastened, as well as sails 21 on the ribs 18 are attached longitudinally.

Every sail 21 is on two adjacent ribs 18 attached laterally. Every sail 21 thus has an upper free edge 22 on, which is radially movable relative to the axis AA.

That's how the sails are 21 under the action of the blood flow between an embodiment for closing the middle blood circulation passage 19 in which the free edges 22 have approached each other in the direction of the axis AA '(in 3 shown in solid lines), and an execution for the release of the blood circulation passage 19 in which the free edges 22 have moved radially away from the axis AA 'and the passage 19 release, mutually movable.

In an implant variant according to the invention 28 , what a 3 is shown, is the flap holder 12 a tubular endoprosthesis, referred to by the English term "stent", on which the closure member 14 from a skin, as defined above, is attached.

This tubular endoprosthesis 30 is of a broken tubular frame 32 formed having a grid of wires with spring properties. The scaffolding 32 is obtained by braiding at least one stainless steel wire, a shape memory alloy, or a polymer. In one variant, the framework becomes 32 by cutting a tube by laser, water jet or other technique.

This framework 32 is between a contracted state in which it - in view of its introduction into the blood circulation channel - has a small diameter, and a dilated state, which represents its rest state in which it has a large diameter, unfoldable.

Advantageously, the framework is 32 between his contracted state and his dilated state spontaneously unfoldable.

The closing organ 14 is also analogous to that in 2 presented by passing it through a scaffold 32 defined inner surface is fixed.

A third example of an implant according to the invention 50 is in 5 shown. This implant 50 is a vessel patch that is based on a foil 52 from the skin of a floating or crawling locust, as defined above. The foil 52 has a thickness that is far smaller than its other dimensions, for example at least five times less than its other dimensions, such as its length or width.

This implant 50 is intended to be sewn to the wall of a blood vessel, in particular to reinforce this wall or to close a cavity formed in this wall.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• US 6165216 [0004]
• FR 0755890 [0030]
• - EP 08104444 [0030]

Claims (9)

Medical implant ( 10 ; 28 ; 50 ) comprising skin of a swimming or crawling animal, wherein the medical implant is selected from the group consisting of a heart valve, a vascular patch, and a ligament. Medical implant ( 10 ; 28 . 50 ) according to claim 1, intended for the replacement of tissues exposed to repeated mechanical stresses. Medical implant ( 10 ; 28 ) according to claim 2, characterized in that it forms a heart valve comprising a flap holder ( 12 ) which is intended to be fixed to a wall of a blood circulation channel, and one of the holder ( 12 ) worn closure member ( 14 ), wherein the closure member ( 14 ) is formed on the basis of said skin, Medical implant ( 28 ) according to claim 3, characterized in that the flap holder ( 12 ) a tubular endoprosthesis ( 30 ). Medical implant ( 10 ; 28 . 50 ) according to any one of the preceding claims, wherein the animal is selected from the group consisting of reptiles and fish. Medical implant ( 10 ; 28 . 50 ) according to any one of the preceding claims, wherein the animal is an eel Medical implant ( 10 ; 28 . 50 ) according to any one of the preceding claims, which has been subjected to a treatment with a crosslinking fixative. Medical implant ( 10 ; 28 . 50 ) according to claim 7, wherein the crosslinking fixing agent is selected from the group consisting of glutaraldehyde, an epoxide-based agent, formaldehyde, or mixtures thereof. Medical implant ( 10 ; 28 . 50 ) according to one of the preceding claims, wherein the fat layer and the deep collagen layer are not present in the skin part.