Stable bicarbonate ion-containing drug solution

Patent metadata

Field	Value
Publication number	US-9795636-B2
Application number	US-201414272026-A
Country	US
Kind code	B2
Filing date	May 7, 2014
Priority date	Oct 5, 2007
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The invention relates to a stable bicarbonate ion-containing drug solution, particularly a bicarbonate-containing drug solution for dialysis in which the stability has been improved by the presence of a phosphate ion. Further, the invention relates to a drug solution for acute blood purification, particularly a dialysate and a substitution liquid for acute blood purification to be mixed before use containing the drug solution. Still further, the invention relates to a dialysate and a substitution liquid for acute blood purification to be mixed before use in which the formation of insoluble fine particles or precipitates is prevented for a long time after mixing and with which hypokalemeia and hypophosphatemia are not caused.

First claim

The invention claimed is:

1. A drug solution for acute blood purification comprising:
sodium ions; potassium ions; chloride ions; bicarbonate ions; calcium ions; magnesium ions; monophosphate ions, and glucose, but comprising no acetate ions and no citrate ions,
wherein the drug solution has
a concentration of the sodium ions in a range from 132 to 143 mEq/L,
a concentration of the potassium ions in a range from 3.5 to 5.0 mEq/L,
a concentration of the chloride ions in a range from 104 to 114.5 mEq/L,
a concentration of the bicarbonate ions in a range from 32 to 35 mEq/L,
a concentration of the calcium ions in a range from 2.5 to 3.5 mEq/L,
a concentration of the magnesium ions in a range from 1 to 1.5 mEq/L, and
a concentration of the monophosphate ions in a range from 2.3 to 4.5 mg/dL,
wherein the concentration of the monophosphate ions is calculated as an inorganic phosphorus concentration.

2. The drug solution according to claim 1 ,
wherein production of insoluble fine particles or precipitates in the drug solution does not occur even after pH of the drug solution rises to 7.5 or more.

3. The drug solution according to claim 1 , which does not cause hypokalemia or hypophosphatemia.

4. The drug solution according to claim 1 , which is tolerated by a patient having acetate intolerance.

5. The drug solution according to claim 1 , which retains a monophosphate ion concentration in plasma without a variation more than 17% over 24 hours from a beginning of an acute blood purification therapy by administering the drug solution to a mammal, which includes a human, as a dialysate or substitution liquid.

6. A method of removing unnecessary or toxic substances from blood in a subject in need of acute blood purification, comprising:
performing the acute blood purification, which continuously purifies the blood of the subject; and
simultaneously administering a drug solution to the blood of the subject continuously,
wherein the drug solution comprises sodium ions, potassium ions, chloride ions, bicarbonate ions, calcium ions, magnesium ions, monophosphate ions, and glucose, but comprising no acetate ions and no citrate ions,
wherein the drug solution has
a concentration of the sodium ions in a range from 132 to 143 mEq/L,
a concentration of the potassium ions in a range from 3.5 to 5.0 mEq/L,
a concentration of the chloride ions in a range from 104 to 114.5 mEq/L,
a concentration of the bicarbonate ions in a range from 32 to 35 mEq/L,
a concentration of the calcium ions in a range from 2.5 to 3.5 mEq/L,
a concentration of the magnesium ions in a range from 1 to 1.5 mEq/L, and
a concentration of the monophosphate ions in a range from 2.3 to 4.5 mg/dL,
wherein the concentration of the monophosphate ions is calculated as an inorganic phosphorus concentration.

7. The drug solution according to claim 1 , wherein the drug solution comprises:
the sodium ions of 138 mEq/L;
the potassium ions of 4 mEq/L;
the chloride ions in a range from 111 to 112.2 mEq/L;
the bicarbonate ions of 32 mEq/L;
the calcium ions of 2.5 mEq/L;
the magnesium ions of 1 mEq/L; and
the monophosphate ions of 4 mg/dL,
wherein the concentration of the monophosphate ions is calculated as an inorganic phosphorus concentration.

8. The method according to claim 6 , wherein the drug solution comprises:
the sodium ions of 138 mEq/L;
the potassium ions of 4 mEq/L;
the chloride ions in a range from 111 to 112.2 mEq/L;
the bicarbonate ions of 32 mEq/L;
the calcium ions of 2.5 mEq/L;
the magnesium ions of 1 mEq/L; and
the monophosphate ions of 4 mg/dL,
wherein the concentration of the monophosphate ions is calculated as an inorganic phosphorus concentration.

Assignees

• Nat Univ Corp Chiba Univ
• Fuso Pharmaceutical Ind

Inventors

• Oda Shigeto
• Sadahiro Tomohito
• Nakamura Masataka
• Tanaka Syuichi
• Tokuoka Shogo
• Otani Hiroya

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K33/10

  Carbonates; Bicarbonates · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K33/06

  Aluminium, calcium or magnesium; Compounds thereof {, e.g. clay} · CPC title