Chemical apparatus and process disinfecting – deodorizing – preser – Process disinfecting – preserving – deodorizing – or sterilizing
Reexamination Certificate
1998-12-01
2001-06-05
Thornton, Krisanne (Department: 1744)
Chemical apparatus and process disinfecting, deodorizing, preser
Process disinfecting, preserving, deodorizing, or sterilizing
C422S025000, C422S040000, C422S041000, C422S256000, C604S028000, C604S029000, C604S408000, C604S409000, C604S410000
Reexamination Certificate
active
06241943
ABSTRACT:
AREA OF INVENTION
The present invention relates to the use of a solution comprising glucose and intended for peritoneal dialysis and having reduced formation of AGE products.
PRIOR ART
Peritoneal dialysis is a treatment performed when the renal capacity of a patient's kidney is impaired. A peritoneal dialysis solution is installed in the patients abdominal cavity via a catheter and exchange between the blood and the dialysis solution takes place across the peritoneal membrane, whereupon the dialysis solution is drained. In order to obtain fluid removal, the dialysis solution comprises an osmotic agent, usually glucose.
It is known that mixing glucose with amino-containing compounds results in a series of non-enzymatic reactions called Maillard reactions, resulting in advanced glucosylation end products, AGEs. Reference is made to WO 93/13421 and WO 95/30153. It is believed that advanced glucosylation end products are involved in the ageing process of mammals.
Advanced glycosylation end products, AGEs, are known as one candidate to cause diabetic complications. These products are derived from non-enzymatic glycosylation of long-lived proteins that are further modified by the advanced stage of the Maillard reactions, resulting in the formation of glucose-derived cross-links with a brown or fluorescent property. These products increase the vascular permeability by several mechanisms, such as the disturbed integration of basement membrane components due to the cross-linking of proteins, the endothelial cell reaction to the AGE receptor-mediated cytokine release from macrophage, or the occupancy of endothelial cell AGE receptors.
The rise of AGEs is also associated with a variety of tissue disorders including vascular damage, dyslipidaemia and beta-2-microglobuline amyloidosis. Moreover, it has been suggested that elevated AGE levels may mediate the suppression of certain normal host defence mechanisms, such as inhibition of certain bacteriocidal activites.
Advanced glycation has also been implicated in the pathology of Alzheimer's disease.
It has also been suggested that AGE generation is enhanced by an increased oxidative stress associated with uraemia.
Formation of advanced glycosylation end products, AGEs, in connection with peritoneal dialysis has been suggested in an article “In vitro formation of advanced glycation end products in peritoneal dialysis fluid” by Edmund J. Lamb, William R. Cattell and Anne B. St. H. Dawney, published in Kidney International, Vol. 47 (1995) pages 1768-1774 (the expressions “glycosylated” and “glycated” are used interchangeably for the same property). This article investigates peritoneal dialysis solutions of conventional composition in which all components are heat sterilized together as a single solution. The article suggests that such conventional peritoneal dialysis fluid does not contain inhibitors or promoters of the early Maillard reaction other than glucose. The article states that late Maillard reaction products are formed to a higher extent in conventional peritoneal dialysis solutions compared to paired PBS controls. Moreover, the article concludes that such AGE product formation is greater in either fresh dialysis fluid or in dialysate which had been removed from patients immediately after installation, than in dialysates which had remained for longer periods in the peritoneal cavity. The formation of protein-derived fluorescence has been used as a marker of AGE product formation. The article further concludes that results suggest either that conventional peritoneal dialysis fluid contains a factor (or factors) which promotes AGE product formation, and that its concentration diminishes during dialysis, or that the concentration of an inhibitor of the reaction increases in the dialysate during dialysis. In the article it is mentioned that glycation of peritoneal membrane proteins may be involved in the etiology of ultrafiltration failure in CAPD and should the Maillard reaction prove to be relevant to the etiology of ultrafiltration failure, it may be possible to include inhibitors of the reaction in the dialysis fluid, such as aminoguanidine.
WO 93/09820, included herein in its entirety by reference, discloses a peritoneal dialysis solution containing glucose or glucose-like compounds, such as glucose polymers. The disclosed solution is sterilised before use. During sterilisation, the glucose component is sterilized separately from the remaining components at a high concentration of glucose, over 20%, and at a low pH. After sterilisation and preferably shortly before use, the components are mixed to form the final, ready-made peritoneal solution to be installed into the abdomen of the patient. The final solution has a pH of about 6.2-6.5.
Separate sterilization of the concentrated glucose component as described in WO 93/09820 results in a ready-made peritoneal dialysis solution having less break-down products from glucose as compared to a conventional peritoneal dialysis solution.
DISCLOSURE OF THE INVENTION
It could be expected that all peritoneal dialysis solutions comprising glucose should induce AGE formation.
However, it has unexpectedly been discovered that the peritoneal dialysis solution according to WO 93/09820 does not result in formation of AGE products in the same extent as conventional peritoneal dialysis solution. Consequently, a peritoneal dialysis solution according to WO 93/09820 can advantageously be used in patients where formation of AGE products is of importance, such as diabetic patients. Such use will avoid AGE related complications, such as vascular damage, dyslipidaemia and beta-2-microglobuline amyloidosis. Consequently, such use constitutes the second medical use of said peritoneal dialysis solution.
Further features and advantages of the invention will be described in more details below with reference to the appended drawings.
REFERENCES:
patent: 5312547 (1994-05-01), Kruger et al.
patent: 5536469 (1996-07-01), Jonsson et al.
patent: 5643201 (1997-07-01), Peabody et al.
Dawnay Anne
Deppisch Reinhold
Forsbäck Gunita
Henle Thomas
Linden Torbjörn
Gambro AB
Lerner David Littenberg Krumholz & Mentlik LLP
Thornton Krisanne
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