CA1112172A - Antidote consisting of particles of activated carbon - Google Patents
Antidote consisting of particles of activated carbonInfo
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- CA1112172A CA1112172A CA318,549A CA318549A CA1112172A CA 1112172 A CA1112172 A CA 1112172A CA 318549 A CA318549 A CA 318549A CA 1112172 A CA1112172 A CA 1112172A
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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
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- 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
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Abstract
AN ANTIDOTE CONSISTING OF PARTICLES OF ACTIVATED CARBON
Abstract of the Disclosure The specification discloses an antidote consisting of essentially spherical activated carbon comprising at least 85% in number of microscopically spherical particles of activated carbon which have smooth and convex-curved surfaces without conspicuous edges and a ratio of the maximum diameter to the minimum diameter of 1.0-1.3, both said essentially spherical and said microscopically spherical particles of activated carbon being 0.05-2 mm in diameter, 500 - 2000 m2/g in surface area and 0.05 - 1.0cc/g in volume of pore cavity determined in the range of pore radius of 100 - 75000.ANG.. The carbon is an effective antidote but does not produce the usual undesirable side effect of constipation when used internally.
Abstract of the Disclosure The specification discloses an antidote consisting of essentially spherical activated carbon comprising at least 85% in number of microscopically spherical particles of activated carbon which have smooth and convex-curved surfaces without conspicuous edges and a ratio of the maximum diameter to the minimum diameter of 1.0-1.3, both said essentially spherical and said microscopically spherical particles of activated carbon being 0.05-2 mm in diameter, 500 - 2000 m2/g in surface area and 0.05 - 1.0cc/g in volume of pore cavity determined in the range of pore radius of 100 - 75000.ANG.. The carbon is an effective antidote but does not produce the usual undesirable side effect of constipation when used internally.
Description
7~
The present invention relates to an antidote which consists of essentially spherical particles of activated carbon. The carbon is useful in removing poisonous or harmful substances from the gastrointestina] tracts, such as the stomach and intestines.
It has been known for a long time that activated carbon is effective as a remedy for intestinal troubles when used internally and is utilized for many thera-peutical purposes. It has been reported that, when internally administered, the activated carbon shows an excellent therapeutical efficacy particularly on bacterial-infectious diseases such as dysentery, cholera, typhoid abdominalis, alimentary intoxication, indigestion, flatus in intestines, chronic gastritis, epilepsy, dizziness, chlorosis, anthrax and the like. In cases of undesirable intake of drugs and poison, the first-aid oral administration of activated carbon produces an antidotal effect. Furthermore, the internal use of activated carbon is effective for removing from the gastrointestinal trActs noxious substances which are ormed due to abnormalities of metabolism caused by various diseases. These effects are considered to be due to the fact that toxines, abnormal metabolites or substances which induce the formation of such toxines and/or abnormal metabolites in the gastrointestinal tracts are adsorbed on the activated carbon, which is completely harmless to living bodies, and the activated carbon orally administered to living hody is discharged outside of the body bearing thereon the above-mentioned noxious substances.
For antidotal purposes, it has hitherto been general to use powdery activated carbon. In its application, the .
: .
powdery activated carbon is mixed with water to facilitate its oral administration. Alternatively, the powdery activated carbon may be shaped into tablets which are readily broken to powdery pieces in the gastrointestinal tracts when swallowed and can develop their inherent ability of adsorption. However, the use of powdery activated carbon involves a side effect of causing constipation, thus presenting a serious disadvantage.
Since the activated carbon is generally internally applied to patients who suffer from various diseases and are thus, more or less, in a decline, the patients suffer great pain due to the constipation involved, and in some cases there may be a danger to life due to the lack of the excreting ability of the patients unless the feces are mechanically removed.
It has now been found that essentially spherical particles of activated carbon comprising at least 85 %, preferably 90 %, in number of microscopically spherical particles of activated carbon hereinafter specified does not exhibit the secondary effect of causing constipation but shows an excellent antidotal effect.
Thus, according to the invention there is provided an antidote, which consists essentially of discreté spherical activated carbon comprising at least 85% in number of microscopically spherical particles of activated carbon which have smooth and convex-curved surfaces without conspicuous edges and a ratio of the maximum diameter to the minimum diameter of 1.0-1.3, both said essentially spherical and said microscopically spherical particles of activated carbon being 0.05 - 2mm in diameter. They are preferably 500 - 2,000 m2/g in surface area and 0.05 - 1.0 cc/g in volume of ' pore cavity determined in the range o~ pore-radius of 100 - 75,000 A.
The essentially spherical particles and the microscop-ically spherical particles are preferably 0.1 to 1.0 mm in diameter and preferably have a pore cavity volume of 0.1 to 0.8 cc/g.
The spherical particles of activated carbon with a size (diameter) smaller than 0.05 mm are not satisfactory in respect to the secondary e~fect of causing constipation although they do show an antidotal effect. When the size is larger than 2 mm, the spheres are hard to administer orally and the intended level of antidotal efficacy can not be developed quickly.
The shape of the particles of activated carbon is one ~; of the important factors for attaining the satisfactory medical efficacy of the present invention. It is necessary that the particles be essentially spherical, and moreover, it is necessary that the essentially spherical particles of activated carbon comprise at least 85 % in number of microscopically spherical particles of activated carbon, both particles oE act~vated carbon having the above-mentioned parameters. That is, the surface area and ; the volume of pore cavity are the important factors in the simultaneous development of a satisfactory antidotal efficacy and the suppression of the secondary effect of causing constipation. If the surface area and the volume of pore cavity are too small, the adsorbing power becomes so small that the practically satisfactory level of antidotal efficacy can not be obtained.
On the contrary, when the surface area and the volume of pore cavity are larger than those defined hereinabove, ,i72 constipation is undesirably caused although the antidotal effect is still present. In addition, it is considered that microscopically spherical activated carbon of such a larger surface area and volume of pore cavity is reduced in physical strength, so that it will readily be broken to pieces during or after internal administration, causing the side effect of constipation.
According to the practice of the present invention, the surface area of both the essentially spherical particles and the microscopically spherical particles of activated carbon is in the range of 500 - 2000 m2/g, preferably 700 - 1,500 m2/g, as determined by a com-mercially available surface area-determining instrument.
The volume of pore cavity is determined by a commerically available mercury porosimeter and is generaly in the range of 0.05 - 1.0 cc/g, preferably 0.1 - 0.8 cc/g with pore-radius of 100 - 75,000 A.
The starting materials for producing the above-mentioned particles of activated carbon having the above-mentioned characteristic properties can be any o ~heknown starting materials ~or activated carbon including sawdust, coal, coconut shell, pitch, organic synthetic polymers and the like.
These materials can be converted into spherical particles of activated carbon. For example, spherical particles of activated carbon can be obtained by a process which comprises the steps of shaping an above-mentioned powdery material into small-sized spheres by the use of a binder such as pitch, heating and baking the spheres for carbonization thereof in an inert atmosphere at a temperature of 800 - 1000C, and activating them in an , . : ~ . :
atmosphere of steam at a temperature of 900 - 1000C.
Alternatively, a process as described in, for example, Japanese Patent Puhlication No. 50-18879, may be employed which comprises shaping pitch in a molten state into small-sized spheres, oxidizing the spheres to render them infusible, heating and baking the spheres for carbonizat;on in an inert atmosphere at a temperature of 800 - 1000C, and activating the carbon in an inert atmosphere at a temperature of 900 - 1000C. The latter process is especially suitable for the production of the spherical particles of activated carbon according to the present invention since it can yield spherical particles of activated carbon having higher sphericity described above, higher physical strength and smoother surfaces.
As a matter of course, since the spherical particles of activated carbon are used internally, they must thus have such a high purity as to be satisfactory from a viewpoint of safety. For instance, the spherical par-ticles of activated carbon should pass a purity test as prescribed in the standard for "Medicinal Carbon" o the ninth revision of the Parmacopoeia of Japan.
The essentially spherical particles of activated carbon according to the present invention may be used internally by any manner ordinarily applied for conventional activated carbon. Most simply, the essentially spherical particles of activated carbon are suspended in drinking water and orally administered.
Alternatively, the essentially spherical particles of activated carbon may be formulated as tablets of a suitable Eorm by known techniques. In this case, it is necessary that the tablets be so Eormulated that they are Z
readily broken to pieces of the original spherical form in the body so as to ensure the desired therapeutical effect. Still atlernatively, the above-mentioned particles of activated carbon may be encapsulated in - cylindrical capsules in the usual manner.
The dose of the essentially spherical particles of activated carbon is dependent on the stage of disease, the necessity of emergaency counteraction, etc., and the particles are generally taken in an amount of 0.5 - 10 g at a time and three times a day. Administration after or between meals is preferred but the particles are, of course, usable at any time in an urgent case.
The fact that the essentially spherical particles of activated carbon specified as above do not cause constipation when administered while still exhibiting the desired antidotal efficacy is totally unexpected.
Although the reason for the effect has not been elucidated, this is presumably because known powdery active carbon tends to absorb the stimulants for the intestines and thus weakens the entero-cinesia and at the same time is thoroughly 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 invention do not serve to increase the cohesion due to the smoothness of the essentially spherical surfaces and adsorb the stimulants for the intestines in a lesser amount, coupled with the advantage that the spheres give a proper stimulation to the intestines, th llS not causing constipation.
The present invention will be described by way of the following Examples, which should not be construed as limitation of the invention.
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~21~:
EXAMPLE l: (preparation of particles_of activated carbon) .
Seven hundred and fifty parts by weight of a pitch (with a softening point of 190C., a content of nitrobenzene-insoluble matter of 30 % by weight, and an H/C atomic ratio of 0.6) obtained by the thermal cracking of a crude oil, and 250 parts by weight of naphthalene were placed in a stainless steel-autoclave equipped with an agitator, and they were mixed and dissolved at 170C.
To the thus formed solution were added 3,000 parts by weight of an 0.5 % aqueous solution of "Gosenol GH- 17"
(polyvinyl alcohol-based suspending agent, product of Nippon Synthetic Chemical Industry Co. Ltd.), followed by violent agitation at 140C. for 3 minutes and then cooling to room temperature still under agitation to obtain par-ticles of pitch. After removing most of the water of the solution by filtration, the particles were immersed in methanol in an amount of 5 times by weight as much as that of the particles, and the thus formed slurry was shaken to remove naphthalene by dissolution in methanol. After air-drying, the particles were heated in a small-slzed rotary kiln up to 300C. at a heating rate of 25C./hr while passing air therein thereby obtaining infusible, spherical particles. Then the passage of air was stopped and the temperature of the kiln was raised to 900C for carbonization while feeding steam to the particles in the kiln. The kiln temperature was maintained at 900C. so as to activate the particles. As a result, spherical par-ticles of activated carbon of high sphericity mentioned above were obtained having a diameter of 0.07 - l.~ mm.
The three specimens of spherical particles of activated carbon indicated in Table 1 were those obtained by sifting the products of the above-mentioned process.
Table 1 Characteristic Properties of Spherical Particles_of Activated Carbon _ -. . ~
Characteristic Properties Specimen 1 Specimen 2 Specimen 3 particle size (mm) 0.07 - 0.250.25 - 0.6 0.6 - 1.2 surface area (m2/g) 750 1600 1300 volume of pore cavity 0.12 0.38 0.27 (cc/g)*l adsorption power (mg/g)*2 indole 340 570 455 octopamine 120 210 150 phen~lethanolamine 1~5 380 290 phenylalanine 150 250 195 tryptophane 200 340 250 ratio of number of micro-scopically spherical par- 95 99 97 ticles to total number of particles (%) *3 . _ _ . .
Note: *l Determined by a mercury porosimeter (Porosimetro Model 70, product Oe Carlo Erba Co., Ltd., Italy) *2 Amount of adsorption determined by the use of an aqueous solution having a concentration of 20 mg/dl and adjusted to pH 7.4 by means of a sodium potassium phosphate buffer solution.
*3 Microscopically spherical particles of activated carbon means that the particles have smooth and convex curved surface without edges and ratio of the maximum diameter to the minimum diameter of 1.0 - 1.3.
The adsorptive ability of the specimens was determined with regard to amines such as indole and octopamine and abnormally accumulating amino acids in the gastrointestinal tracts which are presumed to be generated in the body due to the abnormal metabolism induced by hepatic diseases. It ' ' ~ : ' ' : .'' ' ' will be appreciated that all of the specimens passed the standard tests such as the identification test, purity test, weight loss on drying, and residue on ignition of "Medicinal Carbon" precribed in the Parmacopoeia of Japan (the ninth revision).
ACUTE TOXICITY TEST
A test was conducted on mice using the specimens indicated in Table 1. The test results are shown below, from which it was confirmed that the spherical particles of activated carbon according to the present invention were very high in safety even when administered in large doses.
For the test, commercially available mice of the ICR-JCL strain (weighing 22 + 1 g) were used and the particles of activated carbon of Specimens 1 and 3 of Table 1 were used as they were, except that Specimen 2 was finely ground. These specimens were, respectively and forcibly p.o. administered by a stomach tube. One week after the administration, the mortality of the mice was observed and LD50 was determined by the Litch~leld-Wilcoxon's method. The results are shown in Table 2.
One week after the administrat;on, the mice were killed and autopsied but no specific abnormal findings were obtained in appearance and internal organs with no toxic symptoms involved.
, SpecimenRoute Number of Mice LDso(mg/kg) Specimen l Oral administration 10 ~15,000*
Specimen 2 " 10 >15,000*
Specimen 3 " 10 ~15,000*
. ~
* The dosage of more than 15,000 mg/kg was found to be experimentally very difficult and so the administration test was s-topped at the maximum dosage of 15,000 mg/kg.
No case of death was observed at the highest dosage of 15,000 mg/kg.
EXAMPLE 2 (A~TIDOTAL TEST) Groups of rats of the Wistar strain, weighing 130 - 140g, were used and orally administered with 20 mg/kg of pentobarbital sodium as an aqueous so].ution.
Immediately after the administration, the specimens of Table 1 and medicinal powdery carbon were respectively : suspended in water, each of which was orally administered at the dosage of 200mg/kg to each of the 10 animals of the test group. For reference, a comparative test was simultaneously carried out without the administration of any activated carbon. Then, the ratio of the average value of the maximum concentration of pentobarbital sodium in the blood of the rats in each group to that of animals in the comparative test group was calculated as a removal rate, with the results shown in Table 3. From the results, it will be appreciated that all of the tested specimens of the activated carbon showed a remarkable antidotal effect.
.
.
-7~:
- -- -- _ Activated Medicinal Carbon Specimen 1 Specimen 2 Specimen 3 Powdery Sample Carbon .
Removal 88.5 96.3 93.1 92.2 Rate t~) Ninety minutes after the administration of the activated carbon, the test rats were each anaesthetically killed and the digestive tract of each rat was removed to observe the degree of intra-intestinal transfer of the carbon. That is, the ratio of the transferred distance of the activated carbon to the over-all length from the cardia to the end of the rectum was determined as a transfer rate. As will be apparent from the results shown in Table 4, the specimens of activated carbon of the invention indicated in Table 1 are significantly greater in the transfer rate, thus being less likely to cause constipation as experienced with the known powdery carbon.
SPECIMENS OF ACTIVATED CARBON
._ . . _ _ .".~ .
Activated Medicinal Carbon Specimen 1 Specimen 2 Specimen 3 Powdery Sample Carbon - -Trans~er Rate (~) 69.6 71.4 72,5 55 5 EXAMPLE 3 (clinical cases) Two women, 24 years old and 36 years old respectively, who had suffered from habitual constipation and pimples on their faces were given between meals 3g of the medicinal powdery carbon at a time, three times a day. From the 1~1;217Z
third day after the beginning of the treatment, the number of the pimples was found to be slighly reduced but the patients were constipated more heavily, complaining of an increased pain upon evacuation.
Then, the administration of the medicinal powdery carbon was stopped, and specimen 1 and specimen 3 of the spherical particles of activated carbon in Table of Example 1 were respectively administered to the 24 year-old and the 36 year-old women each at 3g each time, 3 times a day between meals.
In both cases, the number of the pimples was gradually reduced from the fourth day and the pimples disappeared substantially one week after the beginning of the admin-istration. Further, it was reported that symptoms of constipation were also mitigated with the disappearance of the pain on evacuation.
EXAMPLE 4 (clinical case) A man, 42 years old, who had suffered from repeated constipation and diarrhea about every week was admin-istered between meals with 5g of medicinal powdery carbonat a time, three- times a day. As a result, he complained of an increased pain upon evacuation during the period of the constipation. The use of the powdery carbon was stopped and 5g of the spherical particles of activated carbon of specimen 2 indicated in Table 1 of Example 1 was then administered at a time, three times a day between meals. One week after the beginning of administration, he had a regular evacuation with no pain and the symptom of diarrhea substantially disappeared.
EXAMPLE 5 (clinical case) A male 59 year old showed acute hepatitic symptoms and ;172 the impediment of consciousness with a result of a normo test of less than 10% and at stage IV of coma. A compo-sition consisting of 100 g of the spherical particles of activated carbon of specimen 2 in Table 1 of Example 1 30 g of magnesium hydroxide and 60 ml of syrup of lactu-lose was divided into 6 portions and the injection of the portions was begun by a naso-oral tube. No aggravation of the patient's conditions was observed in the course of injection.
Next day, a blood exchange transfusion of 4,000ml was carried out and the administration of a recipe consisting of the spherical particles of activated carbon/magnesium hydroxide/syrup of lactulose was continued with the result that the improvement in EEG was recognized after three days of illness. Thereafter a daily dose of 50 g of the spherical particles of activated carbon 30 g of magnesium hydroxide and 30 ml of syrup of lactulose divided into 6 portions was administered. After five days of illness, the patient was found to be clearly improved in conscious-ness, being able to talk. The normo test was improved remarkably to a level of 32% after seven days of illness no symptom of constipation due to the administration of the particles of activated carbon according to the present invention was observed.
The present invention relates to an antidote which consists of essentially spherical particles of activated carbon. The carbon is useful in removing poisonous or harmful substances from the gastrointestina] tracts, such as the stomach and intestines.
It has been known for a long time that activated carbon is effective as a remedy for intestinal troubles when used internally and is utilized for many thera-peutical purposes. It has been reported that, when internally administered, the activated carbon shows an excellent therapeutical efficacy particularly on bacterial-infectious diseases such as dysentery, cholera, typhoid abdominalis, alimentary intoxication, indigestion, flatus in intestines, chronic gastritis, epilepsy, dizziness, chlorosis, anthrax and the like. In cases of undesirable intake of drugs and poison, the first-aid oral administration of activated carbon produces an antidotal effect. Furthermore, the internal use of activated carbon is effective for removing from the gastrointestinal trActs noxious substances which are ormed due to abnormalities of metabolism caused by various diseases. These effects are considered to be due to the fact that toxines, abnormal metabolites or substances which induce the formation of such toxines and/or abnormal metabolites in the gastrointestinal tracts are adsorbed on the activated carbon, which is completely harmless to living bodies, and the activated carbon orally administered to living hody is discharged outside of the body bearing thereon the above-mentioned noxious substances.
For antidotal purposes, it has hitherto been general to use powdery activated carbon. In its application, the .
: .
powdery activated carbon is mixed with water to facilitate its oral administration. Alternatively, the powdery activated carbon may be shaped into tablets which are readily broken to powdery pieces in the gastrointestinal tracts when swallowed and can develop their inherent ability of adsorption. However, the use of powdery activated carbon involves a side effect of causing constipation, thus presenting a serious disadvantage.
Since the activated carbon is generally internally applied to patients who suffer from various diseases and are thus, more or less, in a decline, the patients suffer great pain due to the constipation involved, and in some cases there may be a danger to life due to the lack of the excreting ability of the patients unless the feces are mechanically removed.
It has now been found that essentially spherical particles of activated carbon comprising at least 85 %, preferably 90 %, in number of microscopically spherical particles of activated carbon hereinafter specified does not exhibit the secondary effect of causing constipation but shows an excellent antidotal effect.
Thus, according to the invention there is provided an antidote, which consists essentially of discreté spherical activated carbon comprising at least 85% in number of microscopically spherical particles of activated carbon which have smooth and convex-curved surfaces without conspicuous edges and a ratio of the maximum diameter to the minimum diameter of 1.0-1.3, both said essentially spherical and said microscopically spherical particles of activated carbon being 0.05 - 2mm in diameter. They are preferably 500 - 2,000 m2/g in surface area and 0.05 - 1.0 cc/g in volume of ' pore cavity determined in the range o~ pore-radius of 100 - 75,000 A.
The essentially spherical particles and the microscop-ically spherical particles are preferably 0.1 to 1.0 mm in diameter and preferably have a pore cavity volume of 0.1 to 0.8 cc/g.
The spherical particles of activated carbon with a size (diameter) smaller than 0.05 mm are not satisfactory in respect to the secondary e~fect of causing constipation although they do show an antidotal effect. When the size is larger than 2 mm, the spheres are hard to administer orally and the intended level of antidotal efficacy can not be developed quickly.
The shape of the particles of activated carbon is one ~; of the important factors for attaining the satisfactory medical efficacy of the present invention. It is necessary that the particles be essentially spherical, and moreover, it is necessary that the essentially spherical particles of activated carbon comprise at least 85 % in number of microscopically spherical particles of activated carbon, both particles oE act~vated carbon having the above-mentioned parameters. That is, the surface area and ; the volume of pore cavity are the important factors in the simultaneous development of a satisfactory antidotal efficacy and the suppression of the secondary effect of causing constipation. If the surface area and the volume of pore cavity are too small, the adsorbing power becomes so small that the practically satisfactory level of antidotal efficacy can not be obtained.
On the contrary, when the surface area and the volume of pore cavity are larger than those defined hereinabove, ,i72 constipation is undesirably caused although the antidotal effect is still present. In addition, it is considered that microscopically spherical activated carbon of such a larger surface area and volume of pore cavity is reduced in physical strength, so that it will readily be broken to pieces during or after internal administration, causing the side effect of constipation.
According to the practice of the present invention, the surface area of both the essentially spherical particles and the microscopically spherical particles of activated carbon is in the range of 500 - 2000 m2/g, preferably 700 - 1,500 m2/g, as determined by a com-mercially available surface area-determining instrument.
The volume of pore cavity is determined by a commerically available mercury porosimeter and is generaly in the range of 0.05 - 1.0 cc/g, preferably 0.1 - 0.8 cc/g with pore-radius of 100 - 75,000 A.
The starting materials for producing the above-mentioned particles of activated carbon having the above-mentioned characteristic properties can be any o ~heknown starting materials ~or activated carbon including sawdust, coal, coconut shell, pitch, organic synthetic polymers and the like.
These materials can be converted into spherical particles of activated carbon. For example, spherical particles of activated carbon can be obtained by a process which comprises the steps of shaping an above-mentioned powdery material into small-sized spheres by the use of a binder such as pitch, heating and baking the spheres for carbonization thereof in an inert atmosphere at a temperature of 800 - 1000C, and activating them in an , . : ~ . :
atmosphere of steam at a temperature of 900 - 1000C.
Alternatively, a process as described in, for example, Japanese Patent Puhlication No. 50-18879, may be employed which comprises shaping pitch in a molten state into small-sized spheres, oxidizing the spheres to render them infusible, heating and baking the spheres for carbonizat;on in an inert atmosphere at a temperature of 800 - 1000C, and activating the carbon in an inert atmosphere at a temperature of 900 - 1000C. The latter process is especially suitable for the production of the spherical particles of activated carbon according to the present invention since it can yield spherical particles of activated carbon having higher sphericity described above, higher physical strength and smoother surfaces.
As a matter of course, since the spherical particles of activated carbon are used internally, they must thus have such a high purity as to be satisfactory from a viewpoint of safety. For instance, the spherical par-ticles of activated carbon should pass a purity test as prescribed in the standard for "Medicinal Carbon" o the ninth revision of the Parmacopoeia of Japan.
The essentially spherical particles of activated carbon according to the present invention may be used internally by any manner ordinarily applied for conventional activated carbon. Most simply, the essentially spherical particles of activated carbon are suspended in drinking water and orally administered.
Alternatively, the essentially spherical particles of activated carbon may be formulated as tablets of a suitable Eorm by known techniques. In this case, it is necessary that the tablets be so Eormulated that they are Z
readily broken to pieces of the original spherical form in the body so as to ensure the desired therapeutical effect. Still atlernatively, the above-mentioned particles of activated carbon may be encapsulated in - cylindrical capsules in the usual manner.
The dose of the essentially spherical particles of activated carbon is dependent on the stage of disease, the necessity of emergaency counteraction, etc., and the particles are generally taken in an amount of 0.5 - 10 g at a time and three times a day. Administration after or between meals is preferred but the particles are, of course, usable at any time in an urgent case.
The fact that the essentially spherical particles of activated carbon specified as above do not cause constipation when administered while still exhibiting the desired antidotal efficacy is totally unexpected.
Although the reason for the effect has not been elucidated, this is presumably because known powdery active carbon tends to absorb the stimulants for the intestines and thus weakens the entero-cinesia and at the same time is thoroughly 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 invention do not serve to increase the cohesion due to the smoothness of the essentially spherical surfaces and adsorb the stimulants for the intestines in a lesser amount, coupled with the advantage that the spheres give a proper stimulation to the intestines, th llS not causing constipation.
The present invention will be described by way of the following Examples, which should not be construed as limitation of the invention.
- ~
~21~:
EXAMPLE l: (preparation of particles_of activated carbon) .
Seven hundred and fifty parts by weight of a pitch (with a softening point of 190C., a content of nitrobenzene-insoluble matter of 30 % by weight, and an H/C atomic ratio of 0.6) obtained by the thermal cracking of a crude oil, and 250 parts by weight of naphthalene were placed in a stainless steel-autoclave equipped with an agitator, and they were mixed and dissolved at 170C.
To the thus formed solution were added 3,000 parts by weight of an 0.5 % aqueous solution of "Gosenol GH- 17"
(polyvinyl alcohol-based suspending agent, product of Nippon Synthetic Chemical Industry Co. Ltd.), followed by violent agitation at 140C. for 3 minutes and then cooling to room temperature still under agitation to obtain par-ticles of pitch. After removing most of the water of the solution by filtration, the particles were immersed in methanol in an amount of 5 times by weight as much as that of the particles, and the thus formed slurry was shaken to remove naphthalene by dissolution in methanol. After air-drying, the particles were heated in a small-slzed rotary kiln up to 300C. at a heating rate of 25C./hr while passing air therein thereby obtaining infusible, spherical particles. Then the passage of air was stopped and the temperature of the kiln was raised to 900C for carbonization while feeding steam to the particles in the kiln. The kiln temperature was maintained at 900C. so as to activate the particles. As a result, spherical par-ticles of activated carbon of high sphericity mentioned above were obtained having a diameter of 0.07 - l.~ mm.
The three specimens of spherical particles of activated carbon indicated in Table 1 were those obtained by sifting the products of the above-mentioned process.
Table 1 Characteristic Properties of Spherical Particles_of Activated Carbon _ -. . ~
Characteristic Properties Specimen 1 Specimen 2 Specimen 3 particle size (mm) 0.07 - 0.250.25 - 0.6 0.6 - 1.2 surface area (m2/g) 750 1600 1300 volume of pore cavity 0.12 0.38 0.27 (cc/g)*l adsorption power (mg/g)*2 indole 340 570 455 octopamine 120 210 150 phen~lethanolamine 1~5 380 290 phenylalanine 150 250 195 tryptophane 200 340 250 ratio of number of micro-scopically spherical par- 95 99 97 ticles to total number of particles (%) *3 . _ _ . .
Note: *l Determined by a mercury porosimeter (Porosimetro Model 70, product Oe Carlo Erba Co., Ltd., Italy) *2 Amount of adsorption determined by the use of an aqueous solution having a concentration of 20 mg/dl and adjusted to pH 7.4 by means of a sodium potassium phosphate buffer solution.
*3 Microscopically spherical particles of activated carbon means that the particles have smooth and convex curved surface without edges and ratio of the maximum diameter to the minimum diameter of 1.0 - 1.3.
The adsorptive ability of the specimens was determined with regard to amines such as indole and octopamine and abnormally accumulating amino acids in the gastrointestinal tracts which are presumed to be generated in the body due to the abnormal metabolism induced by hepatic diseases. It ' ' ~ : ' ' : .'' ' ' will be appreciated that all of the specimens passed the standard tests such as the identification test, purity test, weight loss on drying, and residue on ignition of "Medicinal Carbon" precribed in the Parmacopoeia of Japan (the ninth revision).
ACUTE TOXICITY TEST
A test was conducted on mice using the specimens indicated in Table 1. The test results are shown below, from which it was confirmed that the spherical particles of activated carbon according to the present invention were very high in safety even when administered in large doses.
For the test, commercially available mice of the ICR-JCL strain (weighing 22 + 1 g) were used and the particles of activated carbon of Specimens 1 and 3 of Table 1 were used as they were, except that Specimen 2 was finely ground. These specimens were, respectively and forcibly p.o. administered by a stomach tube. One week after the administration, the mortality of the mice was observed and LD50 was determined by the Litch~leld-Wilcoxon's method. The results are shown in Table 2.
One week after the administrat;on, the mice were killed and autopsied but no specific abnormal findings were obtained in appearance and internal organs with no toxic symptoms involved.
, SpecimenRoute Number of Mice LDso(mg/kg) Specimen l Oral administration 10 ~15,000*
Specimen 2 " 10 >15,000*
Specimen 3 " 10 ~15,000*
. ~
* The dosage of more than 15,000 mg/kg was found to be experimentally very difficult and so the administration test was s-topped at the maximum dosage of 15,000 mg/kg.
No case of death was observed at the highest dosage of 15,000 mg/kg.
EXAMPLE 2 (A~TIDOTAL TEST) Groups of rats of the Wistar strain, weighing 130 - 140g, were used and orally administered with 20 mg/kg of pentobarbital sodium as an aqueous so].ution.
Immediately after the administration, the specimens of Table 1 and medicinal powdery carbon were respectively : suspended in water, each of which was orally administered at the dosage of 200mg/kg to each of the 10 animals of the test group. For reference, a comparative test was simultaneously carried out without the administration of any activated carbon. Then, the ratio of the average value of the maximum concentration of pentobarbital sodium in the blood of the rats in each group to that of animals in the comparative test group was calculated as a removal rate, with the results shown in Table 3. From the results, it will be appreciated that all of the tested specimens of the activated carbon showed a remarkable antidotal effect.
.
.
-7~:
- -- -- _ Activated Medicinal Carbon Specimen 1 Specimen 2 Specimen 3 Powdery Sample Carbon .
Removal 88.5 96.3 93.1 92.2 Rate t~) Ninety minutes after the administration of the activated carbon, the test rats were each anaesthetically killed and the digestive tract of each rat was removed to observe the degree of intra-intestinal transfer of the carbon. That is, the ratio of the transferred distance of the activated carbon to the over-all length from the cardia to the end of the rectum was determined as a transfer rate. As will be apparent from the results shown in Table 4, the specimens of activated carbon of the invention indicated in Table 1 are significantly greater in the transfer rate, thus being less likely to cause constipation as experienced with the known powdery carbon.
SPECIMENS OF ACTIVATED CARBON
._ . . _ _ .".~ .
Activated Medicinal Carbon Specimen 1 Specimen 2 Specimen 3 Powdery Sample Carbon - -Trans~er Rate (~) 69.6 71.4 72,5 55 5 EXAMPLE 3 (clinical cases) Two women, 24 years old and 36 years old respectively, who had suffered from habitual constipation and pimples on their faces were given between meals 3g of the medicinal powdery carbon at a time, three times a day. From the 1~1;217Z
third day after the beginning of the treatment, the number of the pimples was found to be slighly reduced but the patients were constipated more heavily, complaining of an increased pain upon evacuation.
Then, the administration of the medicinal powdery carbon was stopped, and specimen 1 and specimen 3 of the spherical particles of activated carbon in Table of Example 1 were respectively administered to the 24 year-old and the 36 year-old women each at 3g each time, 3 times a day between meals.
In both cases, the number of the pimples was gradually reduced from the fourth day and the pimples disappeared substantially one week after the beginning of the admin-istration. Further, it was reported that symptoms of constipation were also mitigated with the disappearance of the pain on evacuation.
EXAMPLE 4 (clinical case) A man, 42 years old, who had suffered from repeated constipation and diarrhea about every week was admin-istered between meals with 5g of medicinal powdery carbonat a time, three- times a day. As a result, he complained of an increased pain upon evacuation during the period of the constipation. The use of the powdery carbon was stopped and 5g of the spherical particles of activated carbon of specimen 2 indicated in Table 1 of Example 1 was then administered at a time, three times a day between meals. One week after the beginning of administration, he had a regular evacuation with no pain and the symptom of diarrhea substantially disappeared.
EXAMPLE 5 (clinical case) A male 59 year old showed acute hepatitic symptoms and ;172 the impediment of consciousness with a result of a normo test of less than 10% and at stage IV of coma. A compo-sition consisting of 100 g of the spherical particles of activated carbon of specimen 2 in Table 1 of Example 1 30 g of magnesium hydroxide and 60 ml of syrup of lactu-lose was divided into 6 portions and the injection of the portions was begun by a naso-oral tube. No aggravation of the patient's conditions was observed in the course of injection.
Next day, a blood exchange transfusion of 4,000ml was carried out and the administration of a recipe consisting of the spherical particles of activated carbon/magnesium hydroxide/syrup of lactulose was continued with the result that the improvement in EEG was recognized after three days of illness. Thereafter a daily dose of 50 g of the spherical particles of activated carbon 30 g of magnesium hydroxide and 30 ml of syrup of lactulose divided into 6 portions was administered. After five days of illness, the patient was found to be clearly improved in conscious-ness, being able to talk. The normo test was improved remarkably to a level of 32% after seven days of illness no symptom of constipation due to the administration of the particles of activated carbon according to the present invention was observed.
Claims (6)
1. An antidote for oral administration to adsorb exogenous or endogenous toxins in the alimentary canal of a patient without disintegration of said antidote and without causing the patient to become constipated, said antidote consisting essentially of discrete spherical particles of activated carbon, at least 85% of said particles having smooth and convex-curved surfaces without sharp edges, having a ratio of the maximum diameter to the minimum diameter of 1.0 to 1.3, and being of 0.05 to 2.0 mm in diameter.
2. An antidote of claim 1, wherein said particles have a ratio of the maximum diameter to the minimum diameter of 1.0 to 1.3, being of 0.05 to 2.0 mm in diameter, 500 to 2,000 m2/g in specific surface area, 0.05 to 1.0 cc/g in volume of pore cavity determined in the range of pore-radius of 100 to 75,000 .ANG..
3. An antidote of claim 1, wherein said essentially spherical particles of activated carbon comprise at least 90% said spherical particles.
4. An antidote of claim 2, wherein said essentially spherical particles of activated carbon have a particle size in diameter of 0.1-1.0 mm.
5. An antidote of claim 2, wherein said essentially spherical particles of activated carbon have a surface area of 700-1,500 m2/g.
6. An antidote of claim 2, wherein said essentially spherical particles of activated carbon have a volume of pore cavity of 0.1-0.8 cc/g as determined in the range of pore-radius of 100-75,000 .ANG..
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15654677A JPS5489010A (en) | 1977-12-27 | 1977-12-27 | Spherical activated charcoal antidote |
| JP156546/1977 | 1977-12-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1112172A true CA1112172A (en) | 1981-11-10 |
Family
ID=15630152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA318,549A Expired CA1112172A (en) | 1977-12-27 | 1978-12-22 | Antidote consisting of particles of activated carbon |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS5489010A (en) |
| CA (1) | CA1112172A (en) |
| DE (1) | DE2855825C2 (en) |
| ES (1) | ES476321A1 (en) |
| FR (1) | FR2413092A1 (en) |
| GB (1) | GB2012257B (en) |
| NL (1) | NL7812550A (en) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4761284A (en) * | 1977-12-27 | 1988-08-02 | Kureha Kagaku Kogy Kabushiki Kaisha | Antidote including activated carbon particles |
| JPS565313A (en) * | 1979-06-26 | 1981-01-20 | Kureha Chem Ind Co Ltd | Detoxificating spherical active carbon and preparing the same |
| JPS5673542A (en) * | 1979-11-22 | 1981-06-18 | Kureha Chem Ind Co Ltd | Adsorbent |
| JPS5731864A (en) * | 1980-08-04 | 1982-02-20 | Teijin Ltd | Oral activated carbon microcapsule |
| DE3819000A1 (en) * | 1988-06-03 | 1989-12-14 | Hasso Von Bluecher | Bag of a teabag type for eliminating pollutants |
| IT1273678B (en) * | 1993-08-12 | 1997-07-09 | Bluecher Hasso Von | ACTIVATED CARBON PRODUCTION PROCESS |
| NL1000078C2 (en) * | 1994-04-19 | 1996-04-22 | Bluecher Hasso Von | Odor filter for vacuum cleaners. |
| SE515506C2 (en) * | 1994-06-17 | 2001-08-20 | Mhb Filtration Gmbh & Co Kg | Odor filter for ventilation outlet hoods |
| SE509743C2 (en) * | 1994-06-17 | 1999-03-01 | Bluecher Hasso Von | Adsorptionsfilterskikt |
| FR2745981B1 (en) * | 1996-03-15 | 1998-06-05 | ADSORBENT AGENT REDUCING OR ELIMINATING SIDE EFFECTS LINKED TO THE ABSORPTION OF SWEETENERS | |
| JPH1129485A (en) * | 1997-07-10 | 1999-02-02 | Kureha Chem Ind Co Ltd | Antiobestic medicine |
| JP3522708B2 (en) * | 2001-04-11 | 2004-04-26 | 呉羽化学工業株式会社 | Adsorbent for oral administration |
| AU2003280689A1 (en) * | 2002-11-01 | 2004-05-25 | Kureha Chemical Industry Co., Ltd. | Adsorbents for oral administration |
| US7651974B2 (en) | 2002-11-01 | 2010-01-26 | Kureha Chemical Industry Co., Ltd. | Adsorbent for oral administration |
| KR101135260B1 (en) * | 2003-10-22 | 2012-04-12 | 가부시키가이샤 쿠레하 | Adsorbent for oral administration, and agent for treating or preventing renal or liver disease |
| TWI370013B (en) | 2004-04-02 | 2012-08-11 | Kureha Corp | Adsorbent for oral administration, and agent for treating or preventing renal or liver disease |
| TWI370012B (en) | 2004-04-02 | 2012-08-11 | Kureha Corp | Adsorbent for oral administration, and agent for treating or preventing renal or liver disease |
| EP1757362A4 (en) * | 2004-05-31 | 2007-08-22 | Teikoku Medix Co Ltd | Adsorbent and process for producing the same |
| JPWO2005117920A1 (en) * | 2004-06-02 | 2008-04-03 | 株式会社クレハ | Cardiovascular dysfunction factor remover |
| US8247072B2 (en) | 2006-02-14 | 2012-08-21 | Eastman Chemical Company | Resol beads, methods of making them and methods of using them |
| EP2120861A2 (en) * | 2006-11-27 | 2009-11-25 | De Novo Inc. | Decontaminant edible product, methods of production and uses thereof |
| JP5984352B2 (en) * | 2010-10-12 | 2016-09-06 | フタムラ化学株式会社 | Method for producing pharmaceutical adsorbent for oral administration |
| JP5985027B2 (en) * | 2010-10-12 | 2016-09-06 | フタムラ化学株式会社 | Method for producing pharmaceutical adsorbent for oral administration |
| CN104797243A (en) | 2012-09-21 | 2015-07-22 | 辉凌公司 | Pharmaceutical composition |
| EP2978413A1 (en) | 2013-03-25 | 2016-02-03 | Ferring BV | Composition for the treatment of disease |
| KR101924201B1 (en) * | 2014-02-07 | 2018-12-03 | 대원제약주식회사 | Medicinal adsorbent for oral administration with increased strength |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5018879B2 (en) * | 1971-08-27 | 1975-07-02 | ||
| JPS4983690A (en) * | 1972-12-20 | 1974-08-12 | ||
| JPS49126591A (en) * | 1973-04-10 | 1974-12-04 | ||
| JPS5018879A (en) * | 1973-06-20 | 1975-02-27 | ||
| JPS5051996A (en) * | 1973-09-11 | 1975-05-09 | ||
| DE2410372C2 (en) * | 1974-03-05 | 1982-03-04 | Kureha Kagaku Kogyo K.K., Tokyo | Process for reactivating spent practically spherical activated carbon of small size |
| JPS51148291A (en) * | 1975-06-13 | 1976-12-20 | Teijin Ltd | Artificial organ |
| JPS51151693A (en) * | 1975-06-23 | 1976-12-27 | Eisai Co Ltd | Coated bead-like activated carbon for blood purification |
-
1977
- 1977-12-27 JP JP15654677A patent/JPS5489010A/en active Granted
-
1978
- 1978-12-22 DE DE2855825A patent/DE2855825C2/en not_active Expired
- 1978-12-22 CA CA318,549A patent/CA1112172A/en not_active Expired
- 1978-12-22 GB GB7849806A patent/GB2012257B/en not_active Expired
- 1978-12-26 ES ES476321A patent/ES476321A1/en not_active Expired
- 1978-12-26 FR FR7836293A patent/FR2413092A1/en active Granted
- 1978-12-27 NL NL7812550A patent/NL7812550A/en active Search and Examination
Also Published As
| Publication number | Publication date |
|---|---|
| GB2012257A (en) | 1979-07-25 |
| ES476321A1 (en) | 1979-06-16 |
| DE2855825A1 (en) | 1979-06-28 |
| FR2413092A1 (en) | 1979-07-27 |
| GB2012257B (en) | 1983-03-30 |
| FR2413092B1 (en) | 1982-11-19 |
| DE2855825C2 (en) | 1984-03-01 |
| JPS5489010A (en) | 1979-07-14 |
| JPS627169B2 (en) | 1987-02-16 |
| NL7812550A (en) | 1979-06-29 |
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