Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2001-03-20
2004-10-26
Carlson, Karen Cochrane (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
Reexamination Certificate
active
06809076
ABSTRACT:
The present invention relates to the use of anticoagulant agents in the extracorporeal treatment of blood.
Blood in an extracorporeal circulation comes into contact with exogenous surfaces. This activates the blood coagulation system, for example factor XII and blood platelets via the intrinsic pathway of the coagulation cascade. The blood coagulates. The prevention of this is the task of the anticoagulants which are conventionally administered in this situation.
In clinical practice it is virtually always heparin and heparin-like agents which are employed for this purpose, although there are problems with the use thereof. Patients treated with heparin need continuous monitoring in particular because of the generally known risk of HIT, osteoporosis, lipid metabolism disturbances and bleeding complications. It is often necessary to comply with a complicated dosage regimen. Thus, after an initial bolus of 10-20 U/kg, the patients usually receive a further 5-10 U/kg/h in order to maintain a predetermined level in the blood (Mehta R. L., ASAIO Journal, 931-935 (1994)).
In view of these disadvantages there has been a search for favorable alternatives to heparin, and the so-called low molecular weight heparins in particular were found, and these provide not only a prolonged half-life in the blood but also an increased aXa/aIIa ratio. Experiments with other glycosaminoglycans, for example heparan sulfate, dermatan sulfate, chondroitin sulfate and mixtures thereof, were aimed in the same direction. Thus, for example, orgaran has an aXa/aIIa ratio of 22, whereas most low molecular weight heparins are in the range from 1 to 5 (Beijering et al., Seminars in Thrombosis and Hemostasis, Vol. 23, No. 2, 225-233 (1997)).
A corresponding search for a prolonged half-life was successful with hirudins. In contrast to the glycosaminoglycans discussed above, these are peptides, for example natural hirudin obtained from the salivary glands of the medical leech Hirudo medicinalis, or recombinant hirudin. In this connection too, there have been attempts to counteract the relatively short residence time of hirudins in the animal or human body, for example with the aid of derivatized hirudins. In this sense, EP 0 345 616 describes dextran- and Sepharose-derivatized hirudin. The pegylated hirudin muteins described in EP 0 502 962 were also developed with the aim of achieving even longer half-lives, with undiminished activity.
Because of their anticoagulant activity, the substances described above can always be beneficial when anticoagulation is desired. Thus, EP 0 502 962 mentions—in this case for PEG-hirudin—the indications typically listed for anticoagulants, including precisely their use during extracorporeal blood circulation, for example in a hemodialysis or a cardiopulmonary bypass.
Despite the effective protection during the actual dialysis, there is an increasing frequency of reports of a disproportionately high incidence of vascular complications especially in patients with chronic kidney disease. Concerning the occurrence of serious vascular complications, statistical surveys indicate a high risk of 20-30% a year for dialysis patients receiving long-term treatment. About 40-50% of all artifical accesses (shunts) implanted as junction between extracorporeal circulation and vascular system in the USA have to be renewed each year because of a diminution of function (for example through blockage). The mortality rate owing to vascular complications in these hemodialysis patients is about 12% a year. This contributes to the average survival being only 6 years for patients with chronic kidney disease, even with regular hemodialysis. This survival correspond s to that for a metastasizing oncosis.
The object on which the present invention is based, of more comprehensive protection of patients with an extracorporeal circulation and, in particular, dialysis patents receiving long-term treatment, is achieved by the combined therapeutic and prophylactic use of anticoagulant agents.
The present invention therefore relates to the use of anticoagulant agents for the treatment of individuals with an extracorporeal circulation as anticoagulant during the extracorporeal circulation and for prophylaxis of vascular complications after th e extracorporeal circulation.
The treatment period is divided according to the invention into treatment phases in which the blood of the individual to be treated passes through an extracorporeal circulation (extracorporeal treatment phases), and into treatment phases in which the blood is not passed through an extracorporeal circulation (intracorporeal treatment phases).
An extracorporeal circulation means diverting the blood outside a n individual's body. The aim is usually to exclude sections of the body from the bloodstream and/or perform an extracorporeal treatment of the blood. The former use is indicated in particular in operations on the open heart or on major blood vessels, for example for temporary disconnection of the heart by means of a cardiopulmonary bypass (heart-lung machine). The latter use is particularly indicated for extrarenal kidney-function treatment of blood, for example by hemodialysis in cases of renal insufficiency or by hemofiltration in cases of renal insufficiency or other conditions, for example in patients undergoing lipid apheresis.
When blood is in an extracorporeal circulation there is contact between blood or blood constituents and surfaces of the extracorporeal system, which may lead inter alia to an activation of blood coagulation. From the medical viewpoint, this circumstance makes anticoagulant measures necessary, which are aimed in particular at the extracorporeal system during the extracorporeal phase. Anticoagulant agents are used according to the invention as anticoagulant for this purpose. The anticoagulant effect relates in this connection in particular to the prevention of thrombus formation and, where appropriate, diminution of thrombus growth especially in the extracorporeal system.
It is additionally possible to take further expedient anticoagulant measures during the extracorporeal phase on use of a particular anticoagulant agent. The expediency of and necessity for further anticoagulant measures are subject to expert assessment. Thus, further anticoagulants in addition to a particular anticoagulant agent may be used within the framework of further anticoagulant measures. A particular type of further anticoagulant measures may comprise equipping extracorporeal systems or parts thereof with anticoagulants, for example, coating surfaces.
The term “anticoagulant” has the generally accepted meaning for the purpose of the invention. Accordingly, the anticoagulant agents include accepted anticoagulants and agents with a similar effect on blood coagulation of vertebrates, preferably mammals and, in particular, humans.
A particular class of anticoagulant agents comprises the direct thrombin inhibitors, for example hirudins and hirudin, derivatives, especially PEG-hirudin.
In one aspect of the present invention, anticoagulant agents with an extended half-life in the organism to be treated are advantageous for particular treatment regimens according to the invention. Preferred according to the invention for this purpose are anticoagulant agents with a longer half-life than heparins and, in particular, unfractionated heparins and, especially, those with a terminal half-life after intravenous administration of at least about 4 h, even better of at least about 5 h and, in particular, of at least about 6 h. The stated terminal half-lives relate to essentially intact kidney function, that is to say normally a renal elimination efficiency corresponding to a creatinine clearence [sic] CL
CR
of at least about 100 ml/min.
In another aspect of the present invention, anticoagulant agents with an enduring pharmacodynamic activity in the organism to be treated are advantageous for particular treatment regimens according to the invention. Agents with pharmacodynamic activity are those which according to the invention have minimal prophylac
Abel Florian
Bacher Peter
Esslinger Hans-Ulrich
Parow Christopher
Scherhag Rudi
Abbott & GmbH & Co. KG
Carlson Karen Cochrane
Keil & Weinkauf
Snedden Sheridan K
LandOfFree
Use of anticoagulant agents in the extracorporeal treatment... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of anticoagulant agents in the extracorporeal treatment..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of anticoagulant agents in the extracorporeal treatment... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3259873