Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Solid support and method of culturing cells on said solid...
Reexamination Certificate
1999-05-04
2001-06-26
Lankford, Jr., Leon B. (Department: 1651)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Solid support and method of culturing cells on said solid...
C435S403000, C424S093700
Reexamination Certificate
active
06251673
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to a method for manufacturing an implant consisting of a preferably adsorbable carrier material containing medically active agents such as pharmaceutical agents, antibiotics, cytostatics, hormones or the like.
In orthopedic operations, infections of the bone tissue (osteomyelitis) are common, which must be treated with antibiotics. Frequently, antibiotics administered intravenously or orally are without lasting therapeutic effect, even if the pathogen is susceptible. The reason is that the infected sectors are difficult to reach when the blood circulation is poor, when there is scar formation or sclerosis, and when there are membrane-like structures around the bacterial colonies which the antibiotics have difficulty penetrating. For that reason, it is inevitable that to control infections by means of intravenous or oral antibiotics, high doses must be administered on a long-term basis. However, there are limits to large doses due to the systemic side effects that may occur.
When infections occur in the bone tissue, a supplementary surgical intervention is therefore often necessary, in which all infected tissue sections are removed. Surgical debridement inevitably results in bone defects. To compensate for those, bone transplants are used, and this can cause numerous problems. Thus, bone transplants are primarily avital and therefore an ideal breeding ground for renewed bacterial invasion. As a rule, these bone transplants are therefore introduced only in a subsequent step, after the infection has been controlled. Otherwise there is a danger of sequestering the infection and making it persist.
It has therefore already been suggested to apply antibiotics locally in the infected area, but this has resulted in only partial success.
Local instillations are either too short in their effect or they require the application of time-consuming supply systems. At present, practically the only clinical method used consists of antibiotics carriers in the form of polymethylmetacrylate which are incubated with gentamycin. Other antibiotics can hardly be combined with such a carrier, which is reason enough for their limited use. The tissue levels reached are higher than with an intravenous or oral administration of antibiotics, but they are usually still insufficient for eliminating resistant germs. A substantial disadvantage of such antibiotics carriers is that they must be removed again after the patient has been at rest for a few days. To eliminate this disadvantage, some adsorbable implants have been developed very recently which consist of collagen sponges of animal origin, soaked in gentamycin. So far, this method cannot be used with other antibiotics, and such implants are also effective for a few days only.
In other forms of treatment, it is necessary that the implants deliver no or not only locally applied antibiotics, but also other medically active agents. Thus, transplants used to fill bone defects usually possess no osteoinductive potency, i.e. there is no stimulation for bone formation. For that reason, the defects cannot be induced to regenerate themselves. These transplants act only as spacers along which new endogenous tissue is supposed to form. It therefore seems useful to add factors which will stimulate bone regeneration. Some of these have already been identified, and some can even be produced by means of gene technology. However, problems persist in clinical applications, since such substances cannot be applied in a high-enough concentration and not long enough in the required place of activity.
In surgery involving malignant tumours, a high local concentration of cytostatics is desirable in certain cases. In such cases, it is particularly necessary to avoid systemic effects, since the resulting damage to organs can sometimes become life-threatening.
In the case of other active agents, too (hormones, pharmaceutical agents), it is sometimes desirable to produce either a locally limited or a long-term and continuous effect. These goals can be achieved through the implantation of suitable carriers with the desired active agent.
SUMMARY OF THE INVENTION
From U.S. Pat. No. 4,882,149 A, a carrier material is known which is air-dried at 100° C. 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° and 60° C., 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 solutio
Lankford , Jr. Leon B.
Mediphore-Biotechnologie AG
Townsend and Townsend / and Crew LLP
LandOfFree
Method for manufacturing an implant consisting of a carrier... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for manufacturing an implant consisting of a carrier..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for manufacturing an implant consisting of a carrier... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2483726