Title:  Method for manufacturing an implant consisting of a carrier material containing medically active agents

United States Patent:  6,251,673

Assignee:  Mediphore-Biotechnologie AG (Vienna, AT)

Filed:  May 4, 1999

PCT NO:  PCT/AT97/00198

102(e) Date:  May 4, 1999

PCT PUB. Date:  March 19, 1998

Foreign Application Priority Data:  Sep 10, 1996[AU] (1606/96)

The invention concerns an implant consisting of a carrier material containing medical substances such as pharmaceuticals, antibiotics, cytotstatic agents, hormones or the like made out of organic matter, preferably of a biological tissue of human, animal or plant origin, which before being incubated preferably in vacuum with one or the substances, is broken up, cleaned and freeze-dried.

SUMMARY OF THE INVENTION

From U.S. Pat. No. 4,882,149 A, a carrier material is known which is air-dried at 100^oC. after washing. Such a high temperature damages the molecular structures of the carrier material and causes it to wrinkle, by which the cavities of the carrier material, which are the determining factor for the effectiveness of the active agent to be absorbed/adsorbed, are so much reduced in size that only a small quantity of this active agent can be stored in the carrier material. If bone material is used as carrier material, such treatment results in glue, which cannot be absorbed/adsorbed at all by the active agents.

From EP 419 275 A1, a demineralized bone power is known with a medication as another component.

WO 86/07265 discloses an implant that consists of natural bone materials and adsorbed physiological substances such as an antibiotic.

It is an object of the present invention to suggest a method for manufacturing an implant which consists of a carrier material which is preferably adsorbable and with which a local application of medically active agents of many different kinds is made possible in variable doses over variable periods of time. To achieve this objective, it is suggested that an organic material forming the carrier material, in particular a biological tissue of human, animal or plant origin such as bone, sinew, muscle or the like, is comminuted, cleaned and freeze-dried, after which this carrier material is incubated with a solution containing the active agents. By means of such freeze-drying prior to incubation, the organic material forming the carrier material is prepared in such a way that on the one it is as dry as possible and therefore able to absorb/adsorb a very large amount of the active agent, and that on the other hand it is not damaged and completely retains its structures in the molecular as well as in the microscopic and macroscopic range. Such an implant manufactured in accordance with the method according to the invention therefore has the advantage that when the solution containing the effective agent is incubated, a very good enrichment according to its concentration gradient is ensured, whereby the complete rehydration of the freeze-dried material is achieved, and the effective agent is deposited in the organic material in an appropriately high dose, adsorbed and molecularly incorporated if necessary. By choosing the carrier material, the particle size, the concentration of the solution containing the active agent, and the incubation period, the effective intensity and the period of effectiveness of the active agent can be controlled and thus adapted to the requirements at hand.

It is already known that an implant can be freeze-dried after incubation. In this case, freeze-drying serves the purpose of making the implant imperishable, and since incubation of the carrier material occurs prior to freeze-drying, the latter has no effect of the behavior of the carrier material during incubation.

It stands to reason that after comminution, unwanted portions of the carrier material, such as tissue parts between the actual carrier structures (bone trabecula), should be removed, so that the enlarged contact areas result in better perfusion and increased adsorption of the solution containing the active agents.

The necessary cleaning of the organic material is done in a preferred step by means of a washing liquid that is preferably heated to a temperature between 40^o and 60^oC., which can be moved, for example by means of ultrasound and/or by shaking the vessel in which it is to be placed.

It is practical to subject the organic material, prior to freeze-drying, to fat removal by treating it with a fat-dissolving substance, such as ether. On the one hand, this increases the wettability of the surface of the organic material through the solution containing the active agent, and on the other hand, the ability of the organic material to absorb fatty or oily solutions is increased, which means that such fatty and oily solutions can also be stored in the carrier material to a large degree. Subsequently, the organic material can be treated with alcohol and then washed in sterilized water.

Finally, the organic material, after freeze-drying, can be subjected to ionizing radiation, which causes molecular changes in the organic material, resulting in better bonding with the active agent.

The freeze-dried material will be even better able to store the active agents if the freeze-dried material is incubated in a vacuum with a solution containing the active agent, since this means that the solution together with the dissolved active agents can penetrate the deepest structures of the carrier material without hindrance.

It has been shown that favorable results are obtained when the organic material is freeze-dried up to a residual moisture content below 10%, preferably below 5%.

A particularly gentle method of treating the carrier material is to freeze-dry it at a temperature between -20^o and -40^oC., preferably at -30^oC.

Claim 1 of 20 Claims

What is claimed is:

1. A method for manufacturing a medically active implant including a medically active agent comprising the steps of providing an organic material as a carrier material, comminuting the carrier material, cleaning the carrier material, freeze-drying the carrier material, thereafter combining the carrier material with the active agent, and incubating the carrier material and active agent.

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