CN-121985951-A - Dialysate composition comprising specific compounds

Abstract

The invention relates to a dialysate composition having a composition allowing for equilibration with blood, the composition comprising a mineral salt and a pH buffer, and comprising at least one iron oxide nanoparticle (Fe 2+ and/or Fe 3+ ) coated with at least one polymeric compound.

Inventors

• Sylvie Beijin Colin
• Philip Kuquet
• Alion, Ribera del Duero. Zaloshik
• Theo L v Kante
• Ma Nong Kretz
• Maria virtue. Ross Anjiles Ramirez
• Paula Du Enaz Ramirez
• Michele. Feuerbach
• Annie Carlton

Assignees

• 国家科学研究中心
• 斯特拉斯堡大学
• 斯特拉斯堡大学医院
• 国立健康与医学研究所

Dates

Publication Date

20260505

Application Date

20240730

Priority Date

20230801

Claims (13)

1. 1. A dialysate composition for allowing equilibration with blood, said composition comprising at least one mineral salt and at least one pH buffer and comprising at least one iron oxide nanoparticle (Fe 2+ and/or Fe 3 + ) coated with at least one polymeric compound, Wherein the at least one pH buffer is selected from the group consisting of acetate buffers, bicarbonate buffers, citrate buffers, lactate buffers, and mixtures thereof.
2. 2. The dialysate composition of claim 1 further comprising at least one osmotic compound.
3. 3. The dialysate composition of claim 1 or 2, wherein the iron oxide nanoparticles are coated with a polymeric compound or mixture of polymeric compounds.
4. 4. A dialysate composition according to claims 1 to 3 wherein the iron oxide nanoparticles are coated with a polymeric compound selected from tannic acid, polyacrylic acid, carboxymethyl dextran, PDADMAC, PEI, glucuronic acid, gluconic acid and mixtures thereof.
5. 5. The dialysate composition of any one of claims 1 to 4, wherein the iron oxide nanoparticles have a polymer to iron (i.e. polymer to Fe) molar ratio in the range of 0.001 to 5, preferably 0.01 to 2.
6. 6. The dialysate composition of any one of claims 1 to 5, wherein the iron nanoparticles have an average hydrodynamic diameter ranging from 10nm to 300nm, preferably from 20nm to 200nm, and more preferably from 30nm to 150 nm.
7. 7. The dialysate composition of any one of claims 1 to 6, wherein the pH is 4 to 8, preferably 6 to 8, and more preferably 6.5 to 7.
8. 8. The dialysate composition of any one of claims 1 to 7, wherein the concentration of the iron oxide nanoparticles in the dialysate composition is 0.04mmol.l -1 to 4mol.l -1 , preferably 0.04mmol.l -1 to 0.4mol.l -1 , and even more preferably 0.04mmol.l -1 to 20mmol.l -1 .
9. 9. The dialysate composition of any one of claims 1 to 8 for use in hemodialysis or peritoneal dialysis.
10. 10. The dialysate composition of any one of claims 1 to 9, further comprising another nanoparticle selected from the group consisting of inorganic nanoparticles, polymeric capsules, organic-inorganic hybrid nanoparticles, and organic-inorganic hybrid capsules.
11. 11. The dialysate composition according to any one of claims 1 to 10 for use as a medicament.
12. 12. The dialysate composition for the use according to claim 11, wherein the medicament is for delivery via the peritoneal membrane.
13. 13. The dialysate composition according to any one of claims 1 to 10 for use as a dialysate for blood purification or biological fluid purification.

Description

Dialysate composition comprising specific compounds Technical Field The present invention relates to a dialysate composition having a composition allowing for equilibration with blood, said composition comprising a mineral salt, a pH buffer and optionally at least one permeable compound, and comprising at least one iron oxide nanoparticle (Fe 2+/Fe3+) coated with at least one polymeric compound. Typically, the polymeric compound acts as a surfactant. Background Chronic Kidney Disease (CKD) is characterized by a gradual loss of kidney function over time, a major health problem worldwide, with 7500 tens of thousands of people suffering from CKD in europe. This syndrome causes uremic toxins and phosphates, which are normally cleared regularly by healthy kidneys, to accumulate in the blood, leading to the occurrence of toxic symptoms, persistent inflammation, oxidative stress and endothelial dysfunction, ultimately leading to serious clinical complications, including cardiovascular disease and death. Thus, patients with end-stage renal failure are not viable without renal replacement therapy (i.e., transplantation or dialysis). Transplantation is the best choice for the patient, but the waiting list may be long and most patients require some form of dialysis while waiting for transplantation. Dialysis can be performed in two ways, hemodialysis (HD) and Peritoneal Dialysis (PD). Hemodialysis involves purifying blood by extracorporeal circulation, in which a machine is used to filter the blood. In peritoneal dialysis, the process is different in that dialysate is introduced into the patient's peritoneal cavity and exchanged across the peritoneal membrane. Through diffusion and osmosis/convection mechanisms, toxins and excess water enter the dialysate primarily through capillaries. The composition of the dialysate equilibrates with the composition of the blood over a period of hours. While dialysis remains an effective means of treating chronic kidney disease, current methods do not remove sufficiently large amounts of phosphate and toxins. This imbalance of phosphate in the blood can lead to very high cardiovascular mortality and bone disease in the patient. In order to control phosphazenia, patients suffering from CKD must follow a restricted diet, which may lead to malnutrition and greatly reduce their quality of life, or take phosphate binders, but these drugs are not always well-tolerated or effective. Thus, there is an urgent need to improve the treatment of chronic kidney disease to control phosphate accumulation in the blood and to prevent hyperphosphatemia. In addition, there is a particular need to find better dialysate compositions to more effectively capture phosphate from blood and, if possible, also improve the removal of other toxins. The present invention meets these needs. Indeed, as shown in the examples, the inventors have found that the removal of phosphates and potential toxins in blood and biological fluids is improved by the addition of nanomaterials based on iron oxide nanoparticles to formulate new dialysis solutions. Disclosure of Invention A first object of the present invention is to provide a dialysate that allows for equilibration with blood, the composition comprising a mineral salt and a pH buffer, and comprising at least one iron oxide nanoparticle (Fe 2+ and/or Fe 3+) coated with at least one polymeric compound. Preferably, the dialysate composition further comprises at least one osmotic compound. Another object of the invention is a composition for use as a medicament, more preferably as a dialysis fluid for blood purification. Dialysate composition A first object of the present invention is a dialysate composition allowing for equilibration with blood, comprising mineral salts, pH buffers and optionally at least one permeable compound, and comprising at least one iron oxide nanoparticle (Fe 2+ and/or Fe 3+) coated with at least one polymeric compound. By "dialysate composition" is meant an aqueous composition comprising at least one mineral salt (also referred to as an "electrolyte"), a pH buffer, and optionally at least one permeable compound. The purpose of the dialysate composition is to carry toxins and phosphate from the blood into the dialysate. The dialysate composition of the present invention is a composition useful for peritoneal dialysis and/or hemodialysis. Preferably, the dialysate composition according to the invention has a composition similar to blood. By "a composition similar to that of blood" is meant that the composition comprises at least one inorganic salt and a pH buffer in a concentration similar to that of blood. Optionally, the composition further comprises at least one osmotic compound, in particular in a concentration allowing it to equilibrate with blood and allowing exchange between dialysate and blood by diffusion and convection/osmosis. In particular, the dialysate composition is prepared in a manner that facilitates exchange between blood and dia