CA1139673A - Spherical particles of activated carbon suitable for use as an antidotal pharmaceutical composition - Google Patents
Spherical particles of activated carbon suitable for use as an antidotal pharmaceutical compositionInfo
- Publication number
- CA1139673A CA1139673A CA000354378A CA354378A CA1139673A CA 1139673 A CA1139673 A CA 1139673A CA 000354378 A CA000354378 A CA 000354378A CA 354378 A CA354378 A CA 354378A CA 1139673 A CA1139673 A CA 1139673A
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- Prior art keywords
- activated carbon
- spherical particles
- particles
- pore
- pharmaceutical composition
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/44—Elemental carbon, e.g. charcoal, carbon black
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/30—Active carbon
- C01B32/312—Preparation
- C01B32/318—Preparation characterised by the starting materials
- C01B32/33—Preparation characterised by the starting materials from distillation residues of coal or petroleum; from petroleum acid sludge
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/30—Active carbon
- C01B32/354—After-treatment
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/30—Active carbon
- C01B32/354—After-treatment
- C01B32/384—Granulation
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- Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- External Artificial Organs (AREA)
- Carbon And Carbon Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Discrete spherical particles of activated carbon treated with ammonia exhibit high adsorption of noxious substances in the alimentary tract while not causing constipation which is usually associated with a significant intake of conventional activated carbon.
Discrete spherical particles of activated carbon treated with ammonia exhibit high adsorption of noxious substances in the alimentary tract while not causing constipation which is usually associated with a significant intake of conventional activated carbon.
Description
113~?~i73 BACKGROUND OF THE INVENTION:
It has been known for long that the ingestion of acti-vated carbon is effective as a treatment of the diseases of the intestines, and activated carbon has been utili~ed for treating several intestinal diseases. It has been reported that the internal administration of activated carbon exhibits particularly excellent remediàl effects on various bacterial infectious diseases such as dysentery, cholera, typhoid and alimentary intoxications and on digestive disorder, abdominal dropsy, chronic gastritis, épilepsy, dizziness, chlorosis and anthrax. Also a detoxifying effect has been obtained by the emergent internal administration of activated carbon in-the case of ingesting poison or overdose of medicine. Furthermore, the internal administration of activated car~on is effective for absorbing endogenous noxious substances in digestive organs, which are formed according to metabolic abnormality accompanying various other diseases.
The above-mentioned effectiveness of activated carbon is attributed to the adsorption of toxins in the digestive system, of abnormal metabolites or of substances which produce toxin(s) or cause the metabolic abnormality onto the particles of activated carbon which is itself quite non-toxic to living bodies and to the excretion of activated carbon together with the adsorbed toxins and above-mentioned substances to outside of living bodies.
Hitherto, activated carbon for use with the intention of utilizing its detoxicative function has taken a form of fine ,~
11391~'7:3 powder material, and lt was orally administered with water or was taken after formulating to tablets. The activated carbon ingested as tablets is disintegrated to a fine powdery state in the digestive tracts and then exhibits its adsorbency as in the case of ingesting powdery activated carbon with water. However, the ingestion of powdery activated carbon or its tablets causes constipation as a side effect resulting to be a large demerit on the use of activated carbon as an antidote. Particularly, since activated carbon is administered in the cases of various diseases, the patient's physical strength has been consumed in most cases and accordingly, the constipation occurring as the side effect of administration of activated carbon not only gives a conspicuous pain to the patient but also may cause a fatal situation unless the constipation is resolved by mechanical means when the patient has no sufficient power of excretion. Accordingly, the pxovision of activated carbon which exhibits high detoxicating ability .without causing constipation after its ingestion has been strongly desired.
In consideration of the above-mentioned situation, the inventor of the present invention has found that the -specified spherical particles of activated carbon at least ~5% by weight of which consists of truly spherical particles are suitable.for use as an antidote or antidotal composition, which does not cause constipation after being orally admin-istered. The above-mentioned spherical particles of acti-vated carbon have a ratio of the largest span to the smallest 1139~73 span of each particle of 1.0 to 1.3, a mean diameter of 0.05 to
It has been known for long that the ingestion of acti-vated carbon is effective as a treatment of the diseases of the intestines, and activated carbon has been utili~ed for treating several intestinal diseases. It has been reported that the internal administration of activated carbon exhibits particularly excellent remediàl effects on various bacterial infectious diseases such as dysentery, cholera, typhoid and alimentary intoxications and on digestive disorder, abdominal dropsy, chronic gastritis, épilepsy, dizziness, chlorosis and anthrax. Also a detoxifying effect has been obtained by the emergent internal administration of activated carbon in-the case of ingesting poison or overdose of medicine. Furthermore, the internal administration of activated car~on is effective for absorbing endogenous noxious substances in digestive organs, which are formed according to metabolic abnormality accompanying various other diseases.
The above-mentioned effectiveness of activated carbon is attributed to the adsorption of toxins in the digestive system, of abnormal metabolites or of substances which produce toxin(s) or cause the metabolic abnormality onto the particles of activated carbon which is itself quite non-toxic to living bodies and to the excretion of activated carbon together with the adsorbed toxins and above-mentioned substances to outside of living bodies.
Hitherto, activated carbon for use with the intention of utilizing its detoxicative function has taken a form of fine ,~
11391~'7:3 powder material, and lt was orally administered with water or was taken after formulating to tablets. The activated carbon ingested as tablets is disintegrated to a fine powdery state in the digestive tracts and then exhibits its adsorbency as in the case of ingesting powdery activated carbon with water. However, the ingestion of powdery activated carbon or its tablets causes constipation as a side effect resulting to be a large demerit on the use of activated carbon as an antidote. Particularly, since activated carbon is administered in the cases of various diseases, the patient's physical strength has been consumed in most cases and accordingly, the constipation occurring as the side effect of administration of activated carbon not only gives a conspicuous pain to the patient but also may cause a fatal situation unless the constipation is resolved by mechanical means when the patient has no sufficient power of excretion. Accordingly, the pxovision of activated carbon which exhibits high detoxicating ability .without causing constipation after its ingestion has been strongly desired.
In consideration of the above-mentioned situation, the inventor of the present invention has found that the -specified spherical particles of activated carbon at least ~5% by weight of which consists of truly spherical particles are suitable.for use as an antidote or antidotal composition, which does not cause constipation after being orally admin-istered. The above-mentioned spherical particles of acti-vated carbon have a ratio of the largest span to the smallest 1139~73 span of each particle of 1.0 to 1.3, a mean diameter of 0.05 to
2.0 mm, a specific surface area of 500 to 2,000 m2/g and a pore-volume of 0.05 to 1.0 ml/g of pores having a pore-radius of 100 to 75,000 A, and at least 85% by weight of the particles are truly spherical.
Although the spherical particles of activated carbon characterized by the above-mentioned specific properties are suitable as an antidote without accompanying constipation, the inventor's study for further improvement was still continued.
During the course of such a study, the inventor of the present invention has found that the treatment of said particles of activated carbon with ammonia surprisingly resulted in the reduction of the pH of said particles of activated carbon accompanied by the further improvement of the properties of said particles of activated carbon including their selective adsorbency.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention concerns the spherical particles of activated carbon excellent in selective adsorbency to exo-genous and endogenous noxious substances within the living body without causing constipation after be.ing orally administered, thus extremely suitable for use as an antidote or an-tidotal 1139~o'73 composition which removes the above-mentioned noxious sub--` stances from the digestive system to detoxify such substances, and a method for preparing the above-mentioned spherical particles of activated carbon. - `
The followings are the more detailed explanation of the present invention: The spherical particles of activated carbon suitable for the antidote or antidotal composition accord-ing to the present invention are characterized by the following specified properties:
(1) comprising spherical particles and at least 85%
by weight of the particles are truly spherical, (2) the ratio of the largest span of each particle to the smallest span of the particle is in a range of 1.0 to 1.3;
the diameter is in the range of 0.05 to 2.0 mm; the specific surface area is in a range of 500 to 2,000 m2/g and the pore-volume of pores of 100 to 75,000 A in pore-radius is in the range of 0.05 to 1.0 ml/g, and (3~ the pH of the particles of activated carbon is in the range of 6 to 8 attributable to the ammonia treatment.
As is stated above, the ratio of the largest span to the smallest span of each particle of the spherical particles of activated carbon according to the present invention is in a range of 1.0 to 1.3 and the particles are substantially truly spherical with its diameter of 0.05 to 2.0 mm without an~ conspicuous sharp unevenness and with smooth convex sur~ace. In the case where the particle diameter is less than 0.05 mm, its side effect of causing il39~3 constipation is inevitable in spite of its adsorbency, and on the other hand, in the case where its diameter is larger than 2.0 mm, it is not only difficult to be administered orally ~ut also its antidotal efficacy is not exhibited rapidly after ingestion.
That is, the morphological specificity of particles of activated carbon is one of the important factors of antidotal function within the living body. In addition to the morphological specificity, the specific surface area and the pore-volume of particles of activated carbon affect the antidotal activity of the particles of activated carbon and the occurrence of consti-pation. In other words, in the case where the specific surface area and the pore-volume are too small, the adsorbency of the activated carbon is so small that the sufficient antidotal efficacy could not be obtained, and on the other hand, in the case where the above-mentioned two factors are too large, a phenomenon of constipation accompanies the oral administration in spite of not reducing the adsorbency of the activated carbon.
The phenomenon is attributed to the collapse and disintegration of the particles of activated carbon into powders after ingestion due to the reduction of mechanical strength resulting from the too large specific surface area and the too large pore-volume.
The range of the specific surface area and the pore-volume of the particles of activated carbon according to the present invention have been decided from the consideration of the above-mentioned function of the particles of activated carbon within the living body, and the more preferable range of the ~ 1139~i~d specific surface area is 700 to 1,500 m /g and the more preferable range of the pore-volume is 0 1 to 0.8 ml/g in the region of pore-radius of~100 to 75,000 A.
The above-mentioned specific surface area and the pore-volume have been determined, respectively by an usual apparatus for determination of surface area and a mercury porosimeter.
Still more, the pH of the spherical particle of acti-vated carbon according to the present invention is 6 to 8, said range of pH being attained by bringing ammonia into contact with the spherical particles of activated carbon of pH of higher than 8, and the pH value of 6 to 8 attributed to the ammonia treatment may be said specific.
The spherical particles of activated carbon of the present invention of pH of 6 to 8 show a selective adsorbing function on éxogeneous and endogenous noxious substances.
In other words, the spherical particles of activated carbon of pH of 6 to 8 according to the present invention exhibit within the living body an improved adsorbency on the above-mentioned noxious substances as compared with conventional powdery acti-vated carbon or merely spherically formulated or grariulated activated carbon from powdery activated carbon.
It could not have been presumed that the spherical particles of activated carbon showing alkalinity are converted into those showing neutrality by brinying the former into contact with an alkaline reagent, i.e., an aqueous ammonia solution, and shows the above-mentioned change of their pH. Therefore, the 1139~'73 surface state of the spherical particles of activated carbon treated with ammonia should be quite different from that of activated carbon of pH of 8 to 10. Hitherto, the adjustment of pH of activated carbon has been done by the usual means of neutralization by action of acids such as hydrochloric acid, .sulfuric acid in ¢ase of basic activated carbons or by action of alkalies such as sodium hydroxide, potassium hydroxide in case of acidic activated carbons. However, it is usually very difficult to adjust pH of activated carbon by the conventional method, in addition, undesirable contamination due to acidic or alkaline . moiety such as chlorine, sulfuric, sodium and potassium ions occurs in the resultant activated carbon in the conventional method.
Accordingly, the above-mentioned selective adsorbency of the spherical particles of activated carbon of the present invention may be considered to be attributed to the specific state of the surface of said spherical particles of pH of 6 to 8 obtained by the ammonia treatment.
The followings are the explanation of the method for producing the spherical particles of activated carbon according to the present invention:
The method of producing the spherical particIes of activated carbon according to the present.invention comprises the two steps in one of which the starting material.is-formulated into minute spherical particles and the thus formulated minute particles are activated to be minute spherical particles of activated carbon and in the other of which the minute spherical 1139~i7;~
particles of activated carbon is treated with ammonia to adjust the pH of the particle to be 6 to 8.
As the above-mentioned starting material, a publicly known raw material for producing activated carbon such as saw-dust, coal, coconut-shell, pitches and synthetic organic high polymeric substances may be used.
In the first step of production, in cases where saw-dust, coal and coconut-shell, etc. are used as the raw material, the pulverized material is formulated into minute spherical particles by the use of a binder, for instance, pitch, and then the particles are subjected to the carbonization and the carbonized particles are activated by heatir,g at a temperature of 900 to 1,000C in an atmosphere of water vapour, or in cases of using a pitch as the raw material, the pitch is formulated into minute spherical particles in a melt state according to the method disclosed in Japanese Patent Publication No. 50-18879 and the minute spherical particles are carbonized by the above-mentioned procedures after infusibilizèd by oxidation, and then activated to be minute spherical particles of activated carbon of a diameter of 0.05 to 2.0 mm, a pore-volume.of 0.05 to 1.0 ml/g of pores having a pore-radius of 100 to 75,000 A and a pH of 8 to 10.
In the second step of production, the thus obtained spherical particles of activated carbon were brought into contact with an aqueous ammonia solution containing 1 to 1,000, prefer-1139~73 ably 5 to 100 ppm of NH3 and then dried to be minute spherical particles of activated carbon of the same diameter, specific surface area, pore-volume as those of the particles of activated carbon before the ammonia-treatment, however, of pH of 6 to 8.
By using a pitch as the raw material, the ratio of truly spherical particles in the thus obtained minute spherical particles of activated carbon is raised, and the surface of the particles become much more smooth with an improved mechanical strength. Accordingly, as the met-hod for producing the activated carbon for use in the antidote or antidotal composition of the present invention, it is particularly preferable to adopt the latter method of production.
The above-mentioned second step of production is particularly important process of the production of the spherical particles of activated carbon of the present invention.
Although the pH of conventional spherical particles of activated carbon is generally 8 to 10, the value of pH is converted to 6 to 8 in the second step and by such a process, the thus treated particles of activated carbon become to have an excellent property.
The condition of treatment with an aqueous ammonia solution in the above-mentioned second step depends on the state of spherical particles of activated carbon which have been subjected to activation by water vapour, however, usually the concentration of N~3 in the aqueous solution of ammonia is 1 to 1139~73 1,000, preferably 5 to 100 ppm; the volume ratio of the aqueous ammonia solution to the spherical particles of activated carbon is 1 to 50, preferably 2 to 10 at a temperature of treatment of 10 to 50C for a time period of treatment of 0.5 to 5 hours.
In cases where the concentration of NH3 in the aqueous ammonia solution is higher than the above-mentioned range, the pH of the product becomes alkaline and in cases where the con-centration of NH3 is lower than the above-mentioned range, the pH of the product remains still alkaline.
In the production, the thus treated spherical particles of activated carbon by the aqueous ammonia solution is usually dried at a temperature of 100 to 150C and then sifted to be a size suitable for internal administration. Since the sifting is carried out in order that the size of spherical particles of acti-vated carbon is suitable for internal administration, that is, the uniformity of the size of each particle is improved and the ratio of the diameter of the largest particle to that of the smallest particle is made in the range of 1.0 to 3.0, the sifting may be carried out before the treatment with the aqueous ammonia solution.
The thus obtained spherical particles of activated carbon have the above-mentioned specific properties (1) to (3).
In the case where the spherical particles of activated carbon according to the present invention are applied as an anti-dote or antidotal composition, it is preferable to adopt the same method of ingestion as that for ingesting "charcoal for medical use". Although it is most convenient to ingest the .
~1~9~i73 above-mentioned spherical particles of activated carbon after dispersing into drinking water.
A pharmaceutical composition comprising the spherical particles of activated carbon and of a pharmaceutical carrier such as water-soluble or swellable high polymeric substances which dissolve or swell in water or aluminum hydroxide gel which releases the combined particles of activated carbon into free original spherical particulate state after ingestion and showing , a form of, for instance, tablets, granules and capsules is possibly administered internally.
As for said high polymeric substances which dissolve or swell in water, soluble starch, dextrin, gelatin, gluten, gum arabic, methylcellulose, ethylcellulose, carboxy-methylcellulose or its salt, hydroxyethylcellulose, hydroxy-propylmethylcellulose, crystalline cellulose, ~-cellulose, amylose polyvinyl alcohol, polyvinyl acetate, polyethylene glycol, etc.
is possibly used.
The weight ratio of the activated carbon to the above-mentioned pharmaceutical carrier in the above-mentioned com-position is in a range of 100 ; 0 to S0 :50.
The dose level of the spherical particles of activated carbon depends on the degree of disease, the necessity of urgent detoxication, etc., however, usually 0.5 to 10 g/60 kg of body weight at a time, and three times per day. Although it is preferable to ingest between meals, the ingestior. be excepted from the rule in urgent cases.
It has never been expected that the essentially spherical particles of activated carbon specified as above do 11396'73 not cause any constipation when administered while still exhibiting the antidotal efficacy. Although its reason has not been elucidated, this is presumably because the spherical particles of activated carbon of the present invention, retain their adsorbency of exogenous and endogenous toxins even in the presence of substances such as ingested foods, digested foods, feces and bile acids better as compared with conventional powdery activated carbon or simply formulated particles or granules from powdery activated carbon.
Still presumably because the conventional powdery activated carbon or formulated particles or granules of activated carbon which collapse into original powdery carbon in the juices of the alimentary canal tends to adsorb the stimulants for the intestines to weaken the entero-cinesia and at the same time is well mixed with feces, resulting in an increase of cohesion of the feces to cause constipation, on the other hand, the spherical particles of activated carbon according to the present invention does not serve to increase the cohesion and adsorbs the stimulants for the intestines in less amount, coupled with an advantage that the spherical particles of the present invention give a proper stimulation to the intestines, thus not causing constipation.
The above-rnentioned merits of the spherical particles of activated carbon of the present invention are due to smoothness and physico-chemical state of the surface of said spherical particles.
The present invention is explained more in detail while referring to Examples as follows, however, it should be ` - ~
1~;~9~73 understood that the scope of the present invention is not restricted to these Examples.
Example 1: (Production of the spherical particles of activated carbon):
In a stainless-steel autoclave provided with a stirrer, 750 parts by weight of a pitch (with a softening point of 175C
and an atomic ratio of ~/C of 0.63) obtained by high-temperature cracking of crude petroleum oil and 250 parts by weight of naphthalene were introduced and after mixing and dissolving the pitch into naphthalene by heating to a temperature of 170C,
Although the spherical particles of activated carbon characterized by the above-mentioned specific properties are suitable as an antidote without accompanying constipation, the inventor's study for further improvement was still continued.
During the course of such a study, the inventor of the present invention has found that the treatment of said particles of activated carbon with ammonia surprisingly resulted in the reduction of the pH of said particles of activated carbon accompanied by the further improvement of the properties of said particles of activated carbon including their selective adsorbency.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention concerns the spherical particles of activated carbon excellent in selective adsorbency to exo-genous and endogenous noxious substances within the living body without causing constipation after be.ing orally administered, thus extremely suitable for use as an antidote or an-tidotal 1139~o'73 composition which removes the above-mentioned noxious sub--` stances from the digestive system to detoxify such substances, and a method for preparing the above-mentioned spherical particles of activated carbon. - `
The followings are the more detailed explanation of the present invention: The spherical particles of activated carbon suitable for the antidote or antidotal composition accord-ing to the present invention are characterized by the following specified properties:
(1) comprising spherical particles and at least 85%
by weight of the particles are truly spherical, (2) the ratio of the largest span of each particle to the smallest span of the particle is in a range of 1.0 to 1.3;
the diameter is in the range of 0.05 to 2.0 mm; the specific surface area is in a range of 500 to 2,000 m2/g and the pore-volume of pores of 100 to 75,000 A in pore-radius is in the range of 0.05 to 1.0 ml/g, and (3~ the pH of the particles of activated carbon is in the range of 6 to 8 attributable to the ammonia treatment.
As is stated above, the ratio of the largest span to the smallest span of each particle of the spherical particles of activated carbon according to the present invention is in a range of 1.0 to 1.3 and the particles are substantially truly spherical with its diameter of 0.05 to 2.0 mm without an~ conspicuous sharp unevenness and with smooth convex sur~ace. In the case where the particle diameter is less than 0.05 mm, its side effect of causing il39~3 constipation is inevitable in spite of its adsorbency, and on the other hand, in the case where its diameter is larger than 2.0 mm, it is not only difficult to be administered orally ~ut also its antidotal efficacy is not exhibited rapidly after ingestion.
That is, the morphological specificity of particles of activated carbon is one of the important factors of antidotal function within the living body. In addition to the morphological specificity, the specific surface area and the pore-volume of particles of activated carbon affect the antidotal activity of the particles of activated carbon and the occurrence of consti-pation. In other words, in the case where the specific surface area and the pore-volume are too small, the adsorbency of the activated carbon is so small that the sufficient antidotal efficacy could not be obtained, and on the other hand, in the case where the above-mentioned two factors are too large, a phenomenon of constipation accompanies the oral administration in spite of not reducing the adsorbency of the activated carbon.
The phenomenon is attributed to the collapse and disintegration of the particles of activated carbon into powders after ingestion due to the reduction of mechanical strength resulting from the too large specific surface area and the too large pore-volume.
The range of the specific surface area and the pore-volume of the particles of activated carbon according to the present invention have been decided from the consideration of the above-mentioned function of the particles of activated carbon within the living body, and the more preferable range of the ~ 1139~i~d specific surface area is 700 to 1,500 m /g and the more preferable range of the pore-volume is 0 1 to 0.8 ml/g in the region of pore-radius of~100 to 75,000 A.
The above-mentioned specific surface area and the pore-volume have been determined, respectively by an usual apparatus for determination of surface area and a mercury porosimeter.
Still more, the pH of the spherical particle of acti-vated carbon according to the present invention is 6 to 8, said range of pH being attained by bringing ammonia into contact with the spherical particles of activated carbon of pH of higher than 8, and the pH value of 6 to 8 attributed to the ammonia treatment may be said specific.
The spherical particles of activated carbon of the present invention of pH of 6 to 8 show a selective adsorbing function on éxogeneous and endogenous noxious substances.
In other words, the spherical particles of activated carbon of pH of 6 to 8 according to the present invention exhibit within the living body an improved adsorbency on the above-mentioned noxious substances as compared with conventional powdery acti-vated carbon or merely spherically formulated or grariulated activated carbon from powdery activated carbon.
It could not have been presumed that the spherical particles of activated carbon showing alkalinity are converted into those showing neutrality by brinying the former into contact with an alkaline reagent, i.e., an aqueous ammonia solution, and shows the above-mentioned change of their pH. Therefore, the 1139~'73 surface state of the spherical particles of activated carbon treated with ammonia should be quite different from that of activated carbon of pH of 8 to 10. Hitherto, the adjustment of pH of activated carbon has been done by the usual means of neutralization by action of acids such as hydrochloric acid, .sulfuric acid in ¢ase of basic activated carbons or by action of alkalies such as sodium hydroxide, potassium hydroxide in case of acidic activated carbons. However, it is usually very difficult to adjust pH of activated carbon by the conventional method, in addition, undesirable contamination due to acidic or alkaline . moiety such as chlorine, sulfuric, sodium and potassium ions occurs in the resultant activated carbon in the conventional method.
Accordingly, the above-mentioned selective adsorbency of the spherical particles of activated carbon of the present invention may be considered to be attributed to the specific state of the surface of said spherical particles of pH of 6 to 8 obtained by the ammonia treatment.
The followings are the explanation of the method for producing the spherical particles of activated carbon according to the present invention:
The method of producing the spherical particIes of activated carbon according to the present.invention comprises the two steps in one of which the starting material.is-formulated into minute spherical particles and the thus formulated minute particles are activated to be minute spherical particles of activated carbon and in the other of which the minute spherical 1139~i7;~
particles of activated carbon is treated with ammonia to adjust the pH of the particle to be 6 to 8.
As the above-mentioned starting material, a publicly known raw material for producing activated carbon such as saw-dust, coal, coconut-shell, pitches and synthetic organic high polymeric substances may be used.
In the first step of production, in cases where saw-dust, coal and coconut-shell, etc. are used as the raw material, the pulverized material is formulated into minute spherical particles by the use of a binder, for instance, pitch, and then the particles are subjected to the carbonization and the carbonized particles are activated by heatir,g at a temperature of 900 to 1,000C in an atmosphere of water vapour, or in cases of using a pitch as the raw material, the pitch is formulated into minute spherical particles in a melt state according to the method disclosed in Japanese Patent Publication No. 50-18879 and the minute spherical particles are carbonized by the above-mentioned procedures after infusibilizèd by oxidation, and then activated to be minute spherical particles of activated carbon of a diameter of 0.05 to 2.0 mm, a pore-volume.of 0.05 to 1.0 ml/g of pores having a pore-radius of 100 to 75,000 A and a pH of 8 to 10.
In the second step of production, the thus obtained spherical particles of activated carbon were brought into contact with an aqueous ammonia solution containing 1 to 1,000, prefer-1139~73 ably 5 to 100 ppm of NH3 and then dried to be minute spherical particles of activated carbon of the same diameter, specific surface area, pore-volume as those of the particles of activated carbon before the ammonia-treatment, however, of pH of 6 to 8.
By using a pitch as the raw material, the ratio of truly spherical particles in the thus obtained minute spherical particles of activated carbon is raised, and the surface of the particles become much more smooth with an improved mechanical strength. Accordingly, as the met-hod for producing the activated carbon for use in the antidote or antidotal composition of the present invention, it is particularly preferable to adopt the latter method of production.
The above-mentioned second step of production is particularly important process of the production of the spherical particles of activated carbon of the present invention.
Although the pH of conventional spherical particles of activated carbon is generally 8 to 10, the value of pH is converted to 6 to 8 in the second step and by such a process, the thus treated particles of activated carbon become to have an excellent property.
The condition of treatment with an aqueous ammonia solution in the above-mentioned second step depends on the state of spherical particles of activated carbon which have been subjected to activation by water vapour, however, usually the concentration of N~3 in the aqueous solution of ammonia is 1 to 1139~73 1,000, preferably 5 to 100 ppm; the volume ratio of the aqueous ammonia solution to the spherical particles of activated carbon is 1 to 50, preferably 2 to 10 at a temperature of treatment of 10 to 50C for a time period of treatment of 0.5 to 5 hours.
In cases where the concentration of NH3 in the aqueous ammonia solution is higher than the above-mentioned range, the pH of the product becomes alkaline and in cases where the con-centration of NH3 is lower than the above-mentioned range, the pH of the product remains still alkaline.
In the production, the thus treated spherical particles of activated carbon by the aqueous ammonia solution is usually dried at a temperature of 100 to 150C and then sifted to be a size suitable for internal administration. Since the sifting is carried out in order that the size of spherical particles of acti-vated carbon is suitable for internal administration, that is, the uniformity of the size of each particle is improved and the ratio of the diameter of the largest particle to that of the smallest particle is made in the range of 1.0 to 3.0, the sifting may be carried out before the treatment with the aqueous ammonia solution.
The thus obtained spherical particles of activated carbon have the above-mentioned specific properties (1) to (3).
In the case where the spherical particles of activated carbon according to the present invention are applied as an anti-dote or antidotal composition, it is preferable to adopt the same method of ingestion as that for ingesting "charcoal for medical use". Although it is most convenient to ingest the .
~1~9~i73 above-mentioned spherical particles of activated carbon after dispersing into drinking water.
A pharmaceutical composition comprising the spherical particles of activated carbon and of a pharmaceutical carrier such as water-soluble or swellable high polymeric substances which dissolve or swell in water or aluminum hydroxide gel which releases the combined particles of activated carbon into free original spherical particulate state after ingestion and showing , a form of, for instance, tablets, granules and capsules is possibly administered internally.
As for said high polymeric substances which dissolve or swell in water, soluble starch, dextrin, gelatin, gluten, gum arabic, methylcellulose, ethylcellulose, carboxy-methylcellulose or its salt, hydroxyethylcellulose, hydroxy-propylmethylcellulose, crystalline cellulose, ~-cellulose, amylose polyvinyl alcohol, polyvinyl acetate, polyethylene glycol, etc.
is possibly used.
The weight ratio of the activated carbon to the above-mentioned pharmaceutical carrier in the above-mentioned com-position is in a range of 100 ; 0 to S0 :50.
The dose level of the spherical particles of activated carbon depends on the degree of disease, the necessity of urgent detoxication, etc., however, usually 0.5 to 10 g/60 kg of body weight at a time, and three times per day. Although it is preferable to ingest between meals, the ingestior. be excepted from the rule in urgent cases.
It has never been expected that the essentially spherical particles of activated carbon specified as above do 11396'73 not cause any constipation when administered while still exhibiting the antidotal efficacy. Although its reason has not been elucidated, this is presumably because the spherical particles of activated carbon of the present invention, retain their adsorbency of exogenous and endogenous toxins even in the presence of substances such as ingested foods, digested foods, feces and bile acids better as compared with conventional powdery activated carbon or simply formulated particles or granules from powdery activated carbon.
Still presumably because the conventional powdery activated carbon or formulated particles or granules of activated carbon which collapse into original powdery carbon in the juices of the alimentary canal tends to adsorb the stimulants for the intestines to weaken the entero-cinesia and at the same time is well mixed with feces, resulting in an increase of cohesion of the feces to cause constipation, on the other hand, the spherical particles of activated carbon according to the present invention does not serve to increase the cohesion and adsorbs the stimulants for the intestines in less amount, coupled with an advantage that the spherical particles of the present invention give a proper stimulation to the intestines, thus not causing constipation.
The above-rnentioned merits of the spherical particles of activated carbon of the present invention are due to smoothness and physico-chemical state of the surface of said spherical particles.
The present invention is explained more in detail while referring to Examples as follows, however, it should be ` - ~
1~;~9~73 understood that the scope of the present invention is not restricted to these Examples.
Example 1: (Production of the spherical particles of activated carbon):
In a stainless-steel autoclave provided with a stirrer, 750 parts by weight of a pitch (with a softening point of 175C
and an atomic ratio of ~/C of 0.63) obtained by high-temperature cracking of crude petroleum oil and 250 parts by weight of naphthalene were introduced and after mixing and dissolving the pitch into naphthalene by heating to a temperature of 170C,
3,000 parts by weight of an aqueous 0.5% by weight solution of "GOSENOL GH-170" (a polyvinyl alcohol-derived suspension agent, manufactured by Nippon Gosei Company, Japan) were admixed with the solution under agitation. After continued and vigorous agitation for 60 minutes at a temperature of 130C, the content of the autoclave was cooled to room temperature to form spherical particles rich in truly spherical particles. After removing the larger part of water, the remaining particles were immersed into 5 times by weight of methanol and the mixture was shaken to extract naphthalene into methanol. After removing naphthalene, the particles were dried by air flow and then they were heated in a small rotary kiln to a temperature of 300C at a rate of 25C/hour while blowing air into the kiln to obtain infusibilized particles. I'hen, the introduction of air into the kiln was stopped and while introducing water vapour into the kiln the tr~de t~a~l~
91~3 particles were carbonized by raising the temperature of the kiln to 900C and successively activated by maintaining the tempera-ture at 900C to obtain the spherical particles of activated carbon of 0.1 to 1.5 mm in diameter containing truly spherical particles in a high extent. Then, the ratio of the diameter of the largest particle to that of the smallest particle was ad-justed to 1 to 3 by sifting.
A part of the thus adjusted particles of activated carbon was immersed into an aqueous ammonia solution containing 10 ppm of NH3 at the ratio of volume of the aqueous ammonia solution to weight of the particles of activated carbon of 10 ml/g for 3 hours at room temperature. Then, the particles of activated carbon were separated from the aqueous solution and dried for 16 hours at a temperature of 110C to obtain the spherical particles of activated carbon.
The characteristic properties of the thus obtained spherical particles of activated carbon are shown in Table 1, those of the particles of activated carbon not yet treated with ammonia and`powdery charcoal are also shown in Table 1 for comparison as Comparative specimens. In Table 1, the adsorbencies of both spherical particles of activated carbon to creatinine, respectively are illustrated, said creatinine being known as a noxious substance accumulatively ~ormed ln the living body in metabolic abnormality caused by renal diseases.
11~9~i73 Table 1: Specific Properties of Spherical Particles of Activated Carbon Characteristic Specimen 1 of Comparative Comparative .
propertiesthe present specimen 2 specimen 3 invention (4) . (5) Diameter (mm) 0.26 to 0.6 0.25 to 0.6 <0.06 Specific surface area 1,500 1,500 ¦ 950 tm Ig) Pore-volume (ml/g)(l) 0.35 0.35 1.8 10 l Ratio of number of substantially truly98 98 <5 spherical particles (%) Adsorbency (mg/g)(2) 63 52 45 to creatinine .
pH 7.2 . ` 8.9 5.8 .
Notes: (1) Pore-volume of pores having radius of 100 to 75,000 A, determined by "Porosimetro Model 70" made by Carlo Erba.
(2) Adsorbency was determined in an phosphate buffer solution containing each substrate at a concentration of 5 mg/dl at pH of 7.4.
(3) pH of the specimen was determined by the method described in Pharmacopoeia Japonica IX Ed. for "charcoal for pharmacological use", that is:
After immersing 3 g of the specimen in 60 ml of 11396~J
distilled water and keeping for 5 minutes in boiling, an amount of distilled water was added to compensate the loss due to evaporation, and the pH of the liquid phase was determined after filtration. The value of the thus determined pH of the liquid phase was taken as the pH of the specimen to be shown in Table 1.
91~3 particles were carbonized by raising the temperature of the kiln to 900C and successively activated by maintaining the tempera-ture at 900C to obtain the spherical particles of activated carbon of 0.1 to 1.5 mm in diameter containing truly spherical particles in a high extent. Then, the ratio of the diameter of the largest particle to that of the smallest particle was ad-justed to 1 to 3 by sifting.
A part of the thus adjusted particles of activated carbon was immersed into an aqueous ammonia solution containing 10 ppm of NH3 at the ratio of volume of the aqueous ammonia solution to weight of the particles of activated carbon of 10 ml/g for 3 hours at room temperature. Then, the particles of activated carbon were separated from the aqueous solution and dried for 16 hours at a temperature of 110C to obtain the spherical particles of activated carbon.
The characteristic properties of the thus obtained spherical particles of activated carbon are shown in Table 1, those of the particles of activated carbon not yet treated with ammonia and`powdery charcoal are also shown in Table 1 for comparison as Comparative specimens. In Table 1, the adsorbencies of both spherical particles of activated carbon to creatinine, respectively are illustrated, said creatinine being known as a noxious substance accumulatively ~ormed ln the living body in metabolic abnormality caused by renal diseases.
11~9~i73 Table 1: Specific Properties of Spherical Particles of Activated Carbon Characteristic Specimen 1 of Comparative Comparative .
propertiesthe present specimen 2 specimen 3 invention (4) . (5) Diameter (mm) 0.26 to 0.6 0.25 to 0.6 <0.06 Specific surface area 1,500 1,500 ¦ 950 tm Ig) Pore-volume (ml/g)(l) 0.35 0.35 1.8 10 l Ratio of number of substantially truly98 98 <5 spherical particles (%) Adsorbency (mg/g)(2) 63 52 45 to creatinine .
pH 7.2 . ` 8.9 5.8 .
Notes: (1) Pore-volume of pores having radius of 100 to 75,000 A, determined by "Porosimetro Model 70" made by Carlo Erba.
(2) Adsorbency was determined in an phosphate buffer solution containing each substrate at a concentration of 5 mg/dl at pH of 7.4.
(3) pH of the specimen was determined by the method described in Pharmacopoeia Japonica IX Ed. for "charcoal for pharmacological use", that is:
After immersing 3 g of the specimen in 60 ml of 11396~J
distilled water and keeping for 5 minutes in boiling, an amount of distilled water was added to compensate the loss due to evaporation, and the pH of the liquid phase was determined after filtration. The value of the thus determined pH of the liquid phase was taken as the pH of the specimen to be shown in Table 1.
(4) Spherical particles of activated carbon not treated with ammonia.
. (5) Powdery charcoal.
The results of determination of the adsorbencies of the above-mentioned specimens of two kinds of spherical particles of activated carbon and of powdery charcoal to various digestive en-zymes ln vitro are shown in Table 2 for reference. In addition, the adsorbency of a commercial powdery charcoal to the same diges- .
tive enzymes are also shown in Table 2. The values in Table 2 are the determined values expressed by mg/g obtained by determination on each enzyme as a substrate at a concentration of 1 mg/dl in a phosphate buffer solution at pH of 7.4.
1139ti73 ¦ Table 2: Adsorbencies t~ Digestive Enzymes Enz me ¦ Specimen 1 according ¦ Comparative Comparative Y to present invention I specimen 2 specimen 3 Pepsin 8 12 85 Chymotrypsin 8 11 65 Amylase smaller than 1 smaller than 1 5 Lipase 5 7 ¦ 35 l -I .
It is seen from Table 2 that the adsorbency of the spherical particles of activated carbon (pH 7.2) according to the present invention is generally lower than those of spherical particles of activated carbon (pH 8.9) not yet treated with ammonia and of a commercial powdery charcoal to the digestive enzymes.
Acute toxicity of various activated carbons Acute toxicity tests were carried out on mice using the specimens l-and 2 shown in Table 1, and the results are shown in Table 3. As is seen in Table 3, .it was recognized that the spherical particles of activated carbon according to the present invention were extremely safe even when administered in a large amount.
In these tests, each of the specimens of Table 1 was forcibly administered per os to groups of commercial ICR-JCL
female mice of individual body weignt of 22+ 1 g using a stomach ~ 11396'73 tube, and after one week of the administration the mortality of the group of mice was observed. Although all the mice were autopsied after one week, no noticeable abnormal findings were observed on the external appearance or on internal organs without finding any noticeable symptoms of intoxication.
Table 3: Results of Acute Toxicity Tests Route of Nu~oer of LD50 Specimen administra- mice in a tion test group (g/kg) .
Specimen 1 according to the per os 10 larger than 15 present invention _ _ . .
Comparative per os 10 larger than 15 speclmen 2 _ . - .
Note: Since the administration of more than 15 g/kg was extremely difficult, the test was discontinued at 15 g/kg. There were no case of death.
Example 2: (Function of the spherical particles of activated carbon within the living body):
An aqueous solution of pentobarbital sodium was orally administered to groups of female Wistar rats o individual body weight of 130 to 140 g at a dose rate of 20 mg of the medicine per kg body weight, and immediately after, an aqueous suspension of each specimen shown in Table 1 was orally administered at a 1~ 1139~i7:~ ~
dose rate of 200 mg/kg body weight. A group of the rats was kept as the control by administering only pentobarbital sodium. The number of rats in a group was 10. After pre-determined time periods, blood specimens were collected and the concentrations of pentobarbital sodium in the blood specimen were determined to find the mean value of the maximum concentration of the medicine in the blood. The percentage of the mean of maximum concen-trations of the treated group to the mean of maximum concen-trations of the control group is shown in Table 4 as the rate of removal of pentobarbital sodium from the rats.
As is seen in Table 4, the effect of removal of the medicine (referred to the effect of detoxication) was observed on every specimen of the spherical particles of activated carbon, however, the specimen 1 according to the present invention (treated by ammonia) showed a particularly remarkable detoxifying effect as compared to Comparative specimen 2 which has not been treated by ammonia.
Table 4: Rate of Removal of Pentobarbital Sodium by Specimens , .Specimen 1 according to Comparative Comparative Specimenthe present inventionspecimen 2 specimen 3 _ Rate of removal 98.5 95.0 89.9 , In the next place, after 90 minutes of the administra-tion of each specimen of the spherical particles of activated carbon, all the animals were sacrificed by anesthesia and their digestive tracts were removed to observe the intestinal transfer of the administered particles of activated carbon. The ratio (percentage) of the distance from the cardia to the point at which the particles of activated carbon have arrived to the total length of the tract, from the cardia to the rectal end was recorded as the transfer rate, and the results of observation are shown in Table 5. As is seen in Table 5, in the group of rats to which the spherical particles of activated carbon accord-ing to the present invention were administered, the transfer rate is fairly larger than in the Comparative group, showing the less effect of causing constipation.
Table 5: Intratestinal Transfer Rate of Specimen . Specimen 1 according to ¦ Comparative Comparative .
. Specimen the present invention ¦ specimen 2 specimen 3 Transfer rate 75.5 ¦ 72.0 52.1 Example 3: (Adsorbency of the spherical particles of activated carbon):
In order to observe the adsorbency of the spherical particles of activated carbon according to the present invention, the following experiments were carried out in the presence of sodium stearate which is known to inhibit the adsorption of noxious substances by activated carbon in the intestines.
Into a phosphoric acid-buffer solution at pH of 7.4, sodium stearate was dispersed at a concentration of 2% by weight corresponding to the roughly estimated intestinal concentration of sodium stearate, and further, creatinine was dissolved into the solution at a concentration of 15 mg/dl.
Each of the specimen shown in Table 1 was added to the thus prepared solution and after 3 hour-shaking, the mixture was divided into portions of 5 ml.
After adding 3 drops of an aqueous 10% by weight aluminum sulfate solution to each aliquot of 5 ml to precipitate stearic acid, the concentration of creatinine in the supernatant layer of the aliquot was determined colorimetrically. The above-mentioned procedures were carried out at a temperature of 37C
except for the colorimetrical determination. From the values, the minimum concentration of creatinine on each series was obtained to culculate the adsorbed amount of creatinine onto the specimen. The results are shown in Table 6.
As is clearly seen in Table 6, the spherical particles of activatèd carbon according to the present invention is superior to Comparative specimen 2 (not treated with ammonia) and specimen 3 in adsorbency to creatinine. From the result, it is recognizable that the spherical particles of activated carbon according to the present invention, even in the presence of a substance such as sodium stearate which inhibits the ad-sorption of noxious substances such as creatinine by the activated carbon within the intestinal tracts, exhibits an excellent 11;~9~7:~
adsorbency to the noxious substances such as creatinine.
Table 6: Adsorbency to Creatinine in the presence of sodium stearate SpecimenSpecimen l according to Comparative Comparative the present invention specimen 2specimen 3 Amount of adsorbed 18.0 7.8 5.6 creatinine (1) _ _ Note: (1) adsorbed amount of creatinine (mg) onto unit amount (g) of specimen of the particles of activated carbon, and of specimen of the powdery charcoal.
. (5) Powdery charcoal.
The results of determination of the adsorbencies of the above-mentioned specimens of two kinds of spherical particles of activated carbon and of powdery charcoal to various digestive en-zymes ln vitro are shown in Table 2 for reference. In addition, the adsorbency of a commercial powdery charcoal to the same diges- .
tive enzymes are also shown in Table 2. The values in Table 2 are the determined values expressed by mg/g obtained by determination on each enzyme as a substrate at a concentration of 1 mg/dl in a phosphate buffer solution at pH of 7.4.
1139ti73 ¦ Table 2: Adsorbencies t~ Digestive Enzymes Enz me ¦ Specimen 1 according ¦ Comparative Comparative Y to present invention I specimen 2 specimen 3 Pepsin 8 12 85 Chymotrypsin 8 11 65 Amylase smaller than 1 smaller than 1 5 Lipase 5 7 ¦ 35 l -I .
It is seen from Table 2 that the adsorbency of the spherical particles of activated carbon (pH 7.2) according to the present invention is generally lower than those of spherical particles of activated carbon (pH 8.9) not yet treated with ammonia and of a commercial powdery charcoal to the digestive enzymes.
Acute toxicity of various activated carbons Acute toxicity tests were carried out on mice using the specimens l-and 2 shown in Table 1, and the results are shown in Table 3. As is seen in Table 3, .it was recognized that the spherical particles of activated carbon according to the present invention were extremely safe even when administered in a large amount.
In these tests, each of the specimens of Table 1 was forcibly administered per os to groups of commercial ICR-JCL
female mice of individual body weignt of 22+ 1 g using a stomach ~ 11396'73 tube, and after one week of the administration the mortality of the group of mice was observed. Although all the mice were autopsied after one week, no noticeable abnormal findings were observed on the external appearance or on internal organs without finding any noticeable symptoms of intoxication.
Table 3: Results of Acute Toxicity Tests Route of Nu~oer of LD50 Specimen administra- mice in a tion test group (g/kg) .
Specimen 1 according to the per os 10 larger than 15 present invention _ _ . .
Comparative per os 10 larger than 15 speclmen 2 _ . - .
Note: Since the administration of more than 15 g/kg was extremely difficult, the test was discontinued at 15 g/kg. There were no case of death.
Example 2: (Function of the spherical particles of activated carbon within the living body):
An aqueous solution of pentobarbital sodium was orally administered to groups of female Wistar rats o individual body weight of 130 to 140 g at a dose rate of 20 mg of the medicine per kg body weight, and immediately after, an aqueous suspension of each specimen shown in Table 1 was orally administered at a 1~ 1139~i7:~ ~
dose rate of 200 mg/kg body weight. A group of the rats was kept as the control by administering only pentobarbital sodium. The number of rats in a group was 10. After pre-determined time periods, blood specimens were collected and the concentrations of pentobarbital sodium in the blood specimen were determined to find the mean value of the maximum concentration of the medicine in the blood. The percentage of the mean of maximum concen-trations of the treated group to the mean of maximum concen-trations of the control group is shown in Table 4 as the rate of removal of pentobarbital sodium from the rats.
As is seen in Table 4, the effect of removal of the medicine (referred to the effect of detoxication) was observed on every specimen of the spherical particles of activated carbon, however, the specimen 1 according to the present invention (treated by ammonia) showed a particularly remarkable detoxifying effect as compared to Comparative specimen 2 which has not been treated by ammonia.
Table 4: Rate of Removal of Pentobarbital Sodium by Specimens , .Specimen 1 according to Comparative Comparative Specimenthe present inventionspecimen 2 specimen 3 _ Rate of removal 98.5 95.0 89.9 , In the next place, after 90 minutes of the administra-tion of each specimen of the spherical particles of activated carbon, all the animals were sacrificed by anesthesia and their digestive tracts were removed to observe the intestinal transfer of the administered particles of activated carbon. The ratio (percentage) of the distance from the cardia to the point at which the particles of activated carbon have arrived to the total length of the tract, from the cardia to the rectal end was recorded as the transfer rate, and the results of observation are shown in Table 5. As is seen in Table 5, in the group of rats to which the spherical particles of activated carbon accord-ing to the present invention were administered, the transfer rate is fairly larger than in the Comparative group, showing the less effect of causing constipation.
Table 5: Intratestinal Transfer Rate of Specimen . Specimen 1 according to ¦ Comparative Comparative .
. Specimen the present invention ¦ specimen 2 specimen 3 Transfer rate 75.5 ¦ 72.0 52.1 Example 3: (Adsorbency of the spherical particles of activated carbon):
In order to observe the adsorbency of the spherical particles of activated carbon according to the present invention, the following experiments were carried out in the presence of sodium stearate which is known to inhibit the adsorption of noxious substances by activated carbon in the intestines.
Into a phosphoric acid-buffer solution at pH of 7.4, sodium stearate was dispersed at a concentration of 2% by weight corresponding to the roughly estimated intestinal concentration of sodium stearate, and further, creatinine was dissolved into the solution at a concentration of 15 mg/dl.
Each of the specimen shown in Table 1 was added to the thus prepared solution and after 3 hour-shaking, the mixture was divided into portions of 5 ml.
After adding 3 drops of an aqueous 10% by weight aluminum sulfate solution to each aliquot of 5 ml to precipitate stearic acid, the concentration of creatinine in the supernatant layer of the aliquot was determined colorimetrically. The above-mentioned procedures were carried out at a temperature of 37C
except for the colorimetrical determination. From the values, the minimum concentration of creatinine on each series was obtained to culculate the adsorbed amount of creatinine onto the specimen. The results are shown in Table 6.
As is clearly seen in Table 6, the spherical particles of activatèd carbon according to the present invention is superior to Comparative specimen 2 (not treated with ammonia) and specimen 3 in adsorbency to creatinine. From the result, it is recognizable that the spherical particles of activated carbon according to the present invention, even in the presence of a substance such as sodium stearate which inhibits the ad-sorption of noxious substances such as creatinine by the activated carbon within the intestinal tracts, exhibits an excellent 11;~9~7:~
adsorbency to the noxious substances such as creatinine.
Table 6: Adsorbency to Creatinine in the presence of sodium stearate SpecimenSpecimen l according to Comparative Comparative the present invention specimen 2specimen 3 Amount of adsorbed 18.0 7.8 5.6 creatinine (1) _ _ Note: (1) adsorbed amount of creatinine (mg) onto unit amount (g) of specimen of the particles of activated carbon, and of specimen of the powdery charcoal.
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An activated carbon useful as an antidote, comprising spherical particles of activated carbon at least 85% by weight of which consists of substantially truly spherical particles of activated carbon, having smooth and convex-curved surface without conspicuous edges, a ratio of the largest span to the smallest span of each of said particles in the range of 1.0 to 1.3, said spherical particles of activated carbon being of 0.05 to 2 mm in diameter, of 500 to 2,000 m2/g in specific surface area, of 0.05 to 1.0 ml/g in pore-volume of pores having pore-radius of 100 to 75,000 .ANG. and showing pH of 6 to 8 by the treatment with ammonia.
2. A pharmaceutical composition having an antidotal activity without causing constipation in dosage unit form, comprising, as an active ingredient, spherical particles of activated carbon including at least 85% in number of substantially truly spherical particles of activated carbon which has smooth and convex-curved surface without conspicuous edges and a ratio of the largest span to the smallest span of each of said particles in the range of 1.0 to 1.3, a diameter of 0.05 to 2 mm, a specific surface area of 500 to 2,000 m2/g, and a pore-volume of 0 05 to 1.0 ml/g of pores having pore-radius of 100 to 75,000 .ANG. and which show pH of 6 to 8 by the treatment with ammonia.
3. The pharmaceutical composition according to claim 2, wherein said spherical particles of activated carbon includes at least 90% in number of said substantially truly spherical particles of activated carbon.
4. The pharmaceutical composition according to claim 2 or 3, wherein said spherical particles of activated carbon and said microscopically spherical particles of activated carbon have a particle size in diameter of 0.1 to 1.0 mm.
5. The pharmaceutical composition according to claim 2 or 3, wherein said spherical particles of activated carbon and said substantially truly spherical particles of activated carbon have a surface area of 700 to 1,500 m2/g.
6. The pharmaceutical composition according to claim 2 or 3, wherein said spherical particles of activated carbon and said substantially truly spherical particles of activated carbon have a pore-volume of 0.1 to 0.8 ml/g of pores having pore-radius of 100 to 75,000 .ANG..
7. The pharmaceutical composition according to claim 2 or 3, wherein said composition is in dosage unit form suitable for oral administration to adsorb exogenous and/or endogenous toxins in the digestive tracts and remove said toxins therefrom without causing constipation.
8. A method for preparing the spherical particles of pH in the range of 6 to 8, characterized in that spherical particles of activated carbon of pH of higher than 8 are brought into con-tact with an aqueous ammonia solution to adjust the pH of the particle to be 6 to 8.
9. The method according to claim 8, wherein the concentration of ammonia in said aqueous ammonia solution is 1 to 1,000 ppm.
10. The activated carbon according to claim 1, wherein said particles of activated carbon are prepared by using a pitch as the starting material.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8053779A JPS565313A (en) | 1979-06-26 | 1979-06-26 | Detoxificating spherical active carbon and preparing the same |
| JP80537/79 | 1979-06-26 |
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| Publication Number | Publication Date |
|---|---|
| CA1139673A true CA1139673A (en) | 1983-01-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000354378A Expired CA1139673A (en) | 1979-06-26 | 1980-06-19 | Spherical particles of activated carbon suitable for use as an antidotal pharmaceutical composition |
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| Country | Link |
|---|---|
| JP (1) | JPS565313A (en) |
| CA (1) | CA1139673A (en) |
| DE (1) | DE3023848C2 (en) |
| FR (1) | FR2459660A1 (en) |
| GB (1) | GB2053176B (en) |
| IT (1) | IT1131386B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5018879A (en) * | 1973-06-20 | 1975-02-27 | ||
| US3917821A (en) * | 1973-10-23 | 1975-11-04 | Milton Manes | Palatable activated carbon |
| JPS53113193A (en) * | 1977-03-14 | 1978-10-03 | Asahi Chemical Ind | Activated charcoal for artificial viscera |
| JPS5489010A (en) * | 1977-12-27 | 1979-07-14 | Kureha Chem Ind Co Ltd | Spherical activated charcoal antidote |
-
1979
- 1979-06-26 JP JP8053779A patent/JPS565313A/en active Granted
-
1980
- 1980-06-19 CA CA000354378A patent/CA1139673A/en not_active Expired
- 1980-06-25 GB GB8020864A patent/GB2053176B/en not_active Expired
- 1980-06-25 DE DE3023848A patent/DE3023848C2/en not_active Expired
- 1980-06-25 FR FR8014129A patent/FR2459660A1/en active Granted
- 1980-06-26 IT IT23051/80A patent/IT1131386B/en active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8357366B2 (en) | 2004-04-02 | 2013-01-22 | Kureha Corporation | Adsorbent for an oral administration, and agent for treating or preventing renal or liver disease |
| US8440228B2 (en) | 2004-04-02 | 2013-05-14 | Kureha Corporation | Adsorbent for an oral administration, and agent for treating or preventing renal or liver disease |
| US8518447B2 (en) | 2004-04-02 | 2013-08-27 | Kureha Corporation | Method for treating or preventing renal or liver disease |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2459660A1 (en) | 1981-01-16 |
| FR2459660B1 (en) | 1983-11-25 |
| DE3023848C2 (en) | 1985-10-24 |
| JPS565313A (en) | 1981-01-20 |
| JPS6229368B2 (en) | 1987-06-25 |
| GB2053176B (en) | 1983-03-09 |
| IT1131386B (en) | 1986-06-18 |
| DE3023848A1 (en) | 1981-01-08 |
| IT8023051A0 (en) | 1980-06-26 |
| GB2053176A (en) | 1981-02-04 |
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