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Title:  Method for treating renal disease, and pharmaceutical composition for treating renal disease

United States Patent:  6,558,667

Issued:  May 6, 2003

Inventors:  Nakanishi; Tsutomu (Kanagawa, JP)

Assignee:  Kureha Chemical Industry Co., Ltd. (Tokyo, JP)

Appl. No.:  840024

Filed:  April 24, 2001

Abstract

A method for treating a patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required, comprising combining a peritoneal dialysis and an administration of a spherical carbon, is disclosed.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The expression "a patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" as used herein means a patient affected with a renal failure at a stage close to criteria for an initiation of a dialysis therapy, or an early stage after reaching criteria for an initiation of a dialysis therapy. Specifically, the "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means a patient under conditions such that a certain level of a urine volume is maintained, a creatinine clearance is decreased to a certain level or more, due to a deterioration of a renal function, clinical symptoms, such as a stagnation of humor or gastrointestinal symptoms, emerge, and troubles are encountered in daily life; a patient who cannot prevent uremic symptoms due to a renal failure from emerging without an introduction of a dialysis therapy, in particular, a patient suffering from a chronic renal failure.

To the best of the inventor's knowledge, it is not known in the prior art to carry out a combined therapy of a peritoneal dialysis and a spherical carbon administration at an early stage after reaching criteria for an initiation of a dialysis therapy wherein a certain level of a urine volume is maintained. Further, it is not known at all in the prior art that a renal function can be recovered, or in some cases, a patient can be taken off a peritoneal dialysis, by carrying out the combined therapy of the peritoneal dialysis and the spherical carbon administration at an early dialyzing stage.

Therefore, the "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means, for example, a patient affected with a renal failure and having a urine volume of, preferably 800 mL/day or more, more preferably 1000 mL/day or more, most preferably 1500 mL/day or more.

The "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means, for example, a patient affected with a renal failure and having a creatinine clearance (Ccr) of, preferably 5 mL/min or more, more preferably 8 mL/min to 30 mL/min, most preferably 10 mL/min to 25 mL/min.

Further, the "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means, for example, a patient affected with a renal failure and having a BUN of, preferably 40 mg/dL to 150 mg/dL, more preferably 40 mg/dL to 100 mg/dL.

Furthermore, the "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means, for example, a patient affected with a renal failure and having a serum creatinine (s-Cr) of, preferably 3 mg/dL to 10 mg/dL, more preferably 4 mg/dL to 8 mg/dL.

Still further, the "patient suffering from a renal failure progressed to a stage at which an initiation of a dialysis therapy is required" means, for example, a patient not having been treated by a dialysis therapy.

In the present invention, any known peritoneal dialysis can be utilized. The peritoneal dialysis which may be used in the present invention is, for example, a continuous ambulatory peritoneal dialysis (CAPD), an intermittent peritoneal dialysis (IPD), or an automated peritoneal dialysis (APD), such as a continuous cyclic peritoneal dialysis CCPD), or a nightly peritoneal dialysis (NPD). In the present invention, the above-mentioned peritoneal dialysis may be used alone or in a combination thereof. In the present invention, it is unnecessary to carry out, but preferable not to carry out, a hemodialysis in addition to the peritoneal dialysis.

A dialysis solution used in the peritoneal dialysis according to the present invention may be a conventional dialysis solution usually used in a conventional peritoneal dialysis.

In the present invention, a spherical carbon is administered in combination with the peritoneal dialysis.

The spherical carbon used in the present invention is not particularly limited as long as the spherical carbon has a spherical shape that can be used for medical treatment. A medical powdery activated carbon conventionally used as an antidote has the side effect of easily causing constipation. Constipation during an illness is particularly dangerous, and thus the above point is a major defect.

The spherical carbon used in the present invention has a particle diameter of 0.05 to 2 mm. When the particle diameter is less than 0.05 mm, the function for eliminating toxic substances becomes insufficient, but a side effect, such as constipation, easily occurs. When the particle diameter is over 2 mm, not only does administration become difficult, but also the desired pharmacological effect is not quickly obtained. The shape of the spherical carbon is one of the important factors for obtaining the effect of the present invention, and it must be substantially spherical.

In the production of the spherical carbon used in the present invention, any raw material from which activated carbon is obtained may be used, for example, sawdust, coal, coconut shells, petroleum pitches, coal pitches, or synthetic organic polymers. It is preferable to use petroleum hydrocarbons. In the present invention, it is preferable to use activated spherical carbon and/or spherical adsorbent (i.e., spherical carbonaceous adsorbent), more preferably the spherical adsorbent, as the spherical carbon.

The activated spherical carbon that may be used in the present invention has a diameter of 0.05 to 2 mm. The basic method for the production of activated spherical carbon comprises carbonizing a starting material and then activating the carbonized material. As the method used for the activation, it is possible to use various known methods for an activation by, for example, steam, chemicals, air, and carbon dioxide. The activated spherical carbon can be prepared, for example, by the following three methods.

A first method comprises the steps of forming fine spherical particles by pelletizing a powdery material with a binder such as pitch; carbonizing the particles by baking in an inert atmosphere at 600 to 1000oC.; and then activating the carbonized particles in a steam atmosphere at 850 to 1000oC.

A second method comprises, as disclosed in, for example, U.S. Pat. No. 3,917,806, corresponding to Japanese Examined Patent Publication (Kokoku) No. 51-76, forming molten pitch into fine spherical particles; rendering the particles infusible by oxygen; and then carbonizing and activating the infusible particles in the same manner as in the first method.

A third method comprises, as disclosed, for example, in U.S. Pat. No. 4,420,443, corresponding to Japanese Examined Patent Publication (Kokoku) No. 59-10930, forming string-like pitch in a molten state; crushing the string-like pitch; introducing the crushed pitch into hot water to form spherical particles; rendering the particles infusible by oxygen; and then carbonizing and activating the infusible particles in the same manner as in the first method.

The spherical carbonaceous adsorbent which may be used in the present invention preferably has the following parameters: a particle diameter of 0.05 to 2 mm, an amount of pores having a radius of not more than 80 Angstroms accounts for 0.2 to 1.0 mL/g, a total amount of acidic groups (A) of 0.30 to 1.20 meq/g, a total amount of basic groups (B) of 0.20 to 0.70 meq/g, and a ratio of the total amount of acidic groups (A) to the total amount of basic groups (B) of 0.40 to 2.5. The spherical carbonaceous adsorbent is disclosed in, for example, U.S. Pat. No. 4,681,764.

It is possible to prepare the spherical carbonaceous adsorbent which may be used in the present invention, by further oxidizing and reducing at an elevated temperature the activated spherical carbon having a particle diameter of 0.05 to 2 mm and a pore amount of 0.2 to 1.0 mL/g for pores having a radius of not more than 80 Angstroms. It is preferable to adjust, by the above oxidizing and reducing treatment at an elevated temperature, the acidic and basic groups of the resulting spherical carbonaceous adsorbent; namely, a total amount of acidic groups (A) to 0.30 to 1.20 meq/g, a total amount of basic groups (B) to 0.20 to 0.70 meq/g, and a ratio of the total amount of acidic groups (A) to the total amount of basic groups (B) to 0.40 to 2.5. The total amount of acidic groups (A) and the total amount of basic groups (B) are physical properties determined by ordinary methods, as follows:

(A) Total Amount of Acidic Groups (A)

The amount of NaOH consumed, which may be determined by adding 1 g of activated spherical carbon or spherical carbonaceous adsorbent, after being crushed into particles having a less than 200 mesh size, to 50 mL of a 0.05N NaOH solution; shaking the mixture for 48 hours; then filtering out the activated spherical carbon or spherical carbonaceous adsorbent; and titrating until neutralization.

(B) Total Amount of Basic Groups (B)

The amount of HCl consumed, which may be determined by adding 1 g of activated spherical carbon or spherical carbonaceous adsorbent after being crushed into particles having a less than 200 mesh size, to 50 mL of a 0.05N HCl solution; shaking the mixture for 24 hours; then filtering out the activated spherical carbon or spherical carbonaceous adsorbent; and titrating until neutralization.

The above oxidizing treatment at an elevated temperature is carried out by a heating treatment at an elevated temperature in an oxidizing atmosphere. As the source of oxygen, pure oxygen, nitrogen oxide, air, or the like may be used. Further, the above reducing treatment at an elevated temperature is carried out by a heating treatment at an elevated temperature in an atmosphere inert to carbon. As the inert atmosphere for the carbon, nitrogen, argon, helium, or mixtures thereof may be used. The conditions of the above heating-oxidation treatment are an atmosphere containing preferably 0.5 to 25% by volume of oxygen, more preferably 3 to 10% by volume of oxygen, and a temperature of preferably 300 to 700oC., more preferably 400 to 600oC. The reduction treatment is preferably carried out in a nitrogen atmosphere at a temperature of 700 to 1100oC., more preferably 800 to 1000oC.

In the present invention, the spherical carbon is administered orally. The dosage thereof depends on the subject (animal or human), age, individual differences, disease conditions, and so on. For example, the oral dosage in the case of a human is usually 0.2 to 20 g of spherical carbon per day. The daily dosage may be taken up at one time or divided into two to four portions. The dosage may appropriately vary with the disease conditions. The spherical carbon formulation may be administered in any form such as granules, tablets, sugar-coated tablets, capsules, sachets, divided packages, suspensions, or the like. In the case of capsules, the usual gelatin capsules, or if necessary, enteric capsules may be used. In the case of granules, tablets, or sugarcoated tablets, these formulations must be broken into the original fine particles inside the body.

The present invention encompasses the case wherein the spherical carbon is administered to a patient affected with a renal failure but not experiencing a dialysis therapy, and after the conditions of the patient progresses to a stage at which an initiation of a dialysis therapy is required, then a peritoneal dialysis is introduced to the patient while continuing the administration of the spherical carbon. Further, the present invention encompasses the case wherein a peritoneal dialysis is introduced and at the same time an administration of the spherical carbon is commenced to a patient affected with a renal failure but not experiencing a dialysis therapy, but not taking the spherical carbon, after the conditions of the patient progresses to a stage at which an initiation of a dialysis therapy is required.

Claim 1 of 8 Claims

What I claim is:

1. A method for treating a patient suffering from renal failure progressed to a stage at which initiation of dialysis therapy is required, comprising combining peritoneal dialysis and administration of spherical carbon at a stage at which sufficient urine volume and residual renal function are maintained, wherein the urine volume of said patient is 800 mL/day or more and said patient has a creatinine clearance of 5 mL/min or more.
 


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