JPS62223125A - Antidote for oral administration - Google Patents

Abstract

PURPOSE:To provide a peroral antidote containing an NH3-treated spherical activated carbon having specific particle diameter, surface area, pore volume and pH as an active component, free from side effect of constipation and exhibiting excellent antidotal effect. CONSTITUTION:An activated carbon of minute spherical form having a diameter of 0.05-2mm, a surface area of 500-2,000m<2>/g a pore volume of 0.05-1ml/g corresponding to pore radius of 100-75,000Angstrom and pH of 8-10 is produced e.g. by forming small spheres of pitch in molten state, oxidizing and infusibilizing the spherical pitch, carbonizing in an inert atmosphere at 800-1,000 deg.C and activating in steam atmosphere at 900-1,000 deg.C. The produced activated carbon is made to contact with an aqueous solution of NH3 and dried to obtain activated carbon having 6-8pH and the same shape as above. >=85% of the obtained activated carbon has true spherical form wherein the ratio of the maximum diameter and the minimum diameter is 1-1.3. A particular surface can be obtained by the NH3-treatment to acquire excellent adsorptivity compared with a conventional activated carbon.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for removing waste from the system, comprising spherical activated carbon in which at least 85% of the activated carbon is true spheres.
The present invention relates to spherical activated carbon suitable for removing and detoxifying a and its production method.

More precisely (well, the present invention eliminates the fecal secretion side effects that have traditionally been a problem when taking activated charcoal to detoxify harmful substances that exist or are produced within the digestive system such as the stomach and intestines). The present invention relates to a spherical activated carbon suitable for an antidote, in which at least 85% of the activated carbon is true spheres, and a method for producing the same.

Activated charcoal has long been known to be effective in treating intestinal diseases and the like when ingested, and is used to treat many diseases. By taking activated charcoal, you can prevent dysentery, cholera, typhoid fever, bacterial infections such as food poisoning, indigestion, intestinal tension, chronic gastritis, epilepsy,
It has been reported that it has particularly excellent therapeutic effects on dizziness, yellowing disease, charcoal scar disease, etc. Also, drugs,
When ingesting poisonous substances, activated charcoal is taken as an emergency measure to have a detoxifying effect. Furthermore, taking activated charcoal,
It is also effective in removing toxic substances in the digestive system that are produced due to metabolic abnormalities associated with various other diseases.

These effects are due to the fact that toxins, abnormal metabolites, or substances that produce toxins or cause metabolic abnormalities in the digestive system are adsorbed to activated carbon, which has no weight to living organisms, and are released outside the body along with activated carbon. It is believed that.

Conventionally, powdered activated carbon has been used for the purpose of this eff1 effect, and this powdered activated carbon has been taken with water or in the form of a suitable tablet.

Even when taken as a tablet, it is unlocked within the body and turns into powder, which exhibits the same adsorption capacity as when taken with water. However, the use of powdered activated carbon causes constipation as a side effect, which is a major drawback. 1.1 Since activated charcoal is usually taken for various diseases, the physical strength of the patient is often exhausted, and constipation that occurs as a side effect is not only extremely painful for the patient. Conventional activated charcoal has the disadvantage that if the patient does not have enough courage to remove it mechanically, it may become life-threatening. lko.

In view of this situation, in order to solve the above-mentioned drawbacks, the present invention has been developed as a result of intensive research, and has been developed to solve the above-mentioned drawbacks.
A particular spherical activated carbon, preferably 90% true spheres,
(The present invention was achieved by discovering that the detoxifying effect of the detoxifying agent can be reversed and that it does not cause constipation side effects.

The antidote according to the invention is prepared from high molecular weight hydrocarbons, such as pitch, by the following two-step process.

In the first step, the pitch is made into small spherical shapes in a molten state, cooled, oxidized to make it infusible, and then heated to 800~
Carbonized at a temperature of 1000°C, then activated at a temperature of 900-1000°C in an aquatic atmosphere to form a diameter of 0.05-1000°C.
2H, surface area 500-2000m/! 7, pore radius 10 (1-75000 people range teno pore volume 0.05
Produce microspherical activated carbon with ~1.0 ml/g, pH=8-10.

In Dainiku Pd, these spherical activated carbons are contacted with a dilute ammonia aqueous solution containing 1 to 1000 ppm of N+-13, preferably 5 to 100 ppm, and dried to form the same spherical activated carbon as before ammonia treatment. Microspherical activated carbon having a diameter, surface area and pore volume of p 11 = 6 to 8 compared to the spherical activated carbon before annealing is produced.

The product consists of microspherical activated carbon in which at least 85% of the activated carbon is true spheres, the activated carbon has a smooth convex surface with no noticeable edges, a maximum diameter of J5, and a maximum diameter of 7.1. The proportion of small diameter is 1.0-13.

If the particle size (diameter) of the spherical activated carbon is 0.05+m or less, even if it has a detoxifying effect, it is not sufficiently effective in eliminating constipation side effects. Furthermore, if the particle size of the spherical activated carbon exceeds 2 centimeters, it will not only be difficult to take, but also the desired detoxifying effect will not be achieved quickly.

The shape of the activated carbon is one important factor in obtaining the satisfactory pharmaceutical effects of the present invention, and in fact it is necessary that it be spherical. More specifically, it is necessary that at least 85% of the aged coal be true grains.

Similar to the shape, the surface area and pore volume of activated carbon (1-4) are also important factors in achieving sufficient detoxification and eliminating constipation side effects at the same time. In other words, if the surface area and pore volume of activated carbon are too small, the adsorption power will be weak, making it difficult to put into practical use.
A sufficient detoxification effect cannot be achieved, and if the surface area and pore volume are too large, constipation will occur even if the detoxification effect is achieved. Furthermore, when the surface area and pore volume of the activated carbon are larger than the ranges of the present invention, the strength decreases, the shape collapses during or after ingestion, and powdering occurs, which is also considered to be a cause of constipation side effects.

The surface area of the microspherical activated carbon of the present invention is 500 to 200074/3 when measured using a commercially available surface area measuring device.
Preferably it is 700-1500 g. When measured with a commercially available mercury intrusion porosimeter, the pore volume is O, OS ~ 1.0 m in the pore radius range of 100 to 75,000 m.
/41? , preferably 0.1 to 0.8 d/d/d.

As raw materials used for producing activated carbon having such characteristics, any known raw materials such as sawdust, coal, coconut shells, pitches, organic synthetic polymers, etc. may be used, and spherical activated carbon can be produced from these materials 71. I can do it.

For example, the initial method for manufacturing spherical activated carbon was to granulate powdered raw materials into small spherical shapes using a binder such as pitch, then heat and sinter them at 800 to 1000°C in an inert atmosphere to carbonize them, and then carbonize them in a steam atmosphere. Inside 900-・1000
There is a method of activating at °C.

On the other hand, for example, by the method disclosed in Japanese Patent Publication No. 50-18879, pitches are made into small spherical shapes in a molten state, and after being made infusible by oxidation, they are
Carbonized by heating and firing at 00°C and heated to 900°C in a steam atmosphere.
Spherical activated carbon can be produced by a method of activation at ~1000°C.

In particular, the method of the present invention is suitable as the jTXi method for producing activated carbon of the present invention, since it yields spherical activated carbon with high sphericity, high strength, and a smooth surface.

The second step of the method for producing microspherical activated carbon of the present invention is a particularly important process. 1]11 of spherical activated carbon is normally n11=8 to 10, but this is changed to pl+=6 to 8. By performing this second step, the spherical activated carbon has improved properties.

The conditions for treatment with an ammonia aqueous solution vary depending on the state of the steam-treated spherical activated carbon, but usually the NH3 concentration of the ammonia aqueous solution is 1 to 10,001) l)m,
Preferably, it is 5 to 100 ppm, and the proportion of ammonia aqueous solution and spherical activated carbon is 1 to 50 ppm. Preferably go to 2/1
0, the processing temperature is 10-50°C, and the processing time is 0.5
~5 hours. When the concentration of N i-13 in the aqueous ammonia solution increases within the above-mentioned range, the pl+ of the product increases.
As the concentration of N[13 increases, the pH of the product remains in the alkaline region, and as the concentration of N[13 decreases.

Spherical activated carbon that exhibits alkalinity becomes acidic by contacting it with an alkaline reagent, such as an aqueous ammonia solution.
The reason for the change to neutral spherical activated carbon is not clear, and furthermore, such a change in pl+ was completely unexpected.

Next, the spherical activated carbon thus treated with the ammonia aqueous solution is dried at a temperature of usually 100 to 150°C, and sieved into four sizes suitable for administration. Adjusting the product to a uniform size, ie sieving to a range of sizes, is preferred for dosing.

For sieving, the ratio of the diameter of the largest particle to the smallest particle is 1 to 1.
In order to obtain spherical activated carbon as shown in Example 3, it is carried out before the ammonia aqueous solution treatment.

In any case, since the spherical activated carbon is to be taken, it must of course be of sufficient purity for safety.
It must pass the purity test specified in section .

The method for taking the spherical activated carbon according to the present invention may be the same known method as for ordinary activated carbon. The most convenient method is to suspend the microspherical activated carbon according to the present invention in drinking water.
Spherical activated carbon may be taken as a suitably shaped tablet in a conventional manner. However, in this case, of course, the spherical activated carbon of the present invention needs to be unlocked into the original spherical activated carbon particles within the body in order to exhibit its effects.

It may also be taken in a conventional cylindrical capsule in a conventional manner.

The dosage m of spherical activated carbon varies depending on the severity of the disease, the need for emergency detoxification, etc., but is usually once, about 0.5 to 3 times a day. Also, it is preferable to take the drug between meals, but of course this does not apply if there is an emergency.

It was completely unexpected that the spherical activated carbon of the present invention maintains its detoxification effect and shows a remarkable effect on eliminating side effects of inertia, and although the cause is still not clear, the spherical activated carbon of the present invention can be effectively treated with ammonia. Since the surface is in a special state, it has the ability to adsorb exogenous and endogenous harmful substances. That is, the spherical activated carbon of the present invention can be used in the presence of ingested plants, digested plants, and their digested products, as well as conventional powdered activated carbon or! The adsorption capacity of powdered activated carbon is reduced compared to that of spherical or lumped activated carbon. Conventional powdered charcoal or spheroidized or agglomerated powdered charcoal also adsorbs substances that stimulate intestinal motility, weakening intestinal motility, and at the same time mix well with stool, increasing the cohesive force of stool and causing constipation. On the other hand, the spherical activated carbon of the present invention has different surface properties. Because it is a smooth sphere, it does not have the effect of increasing the cohesive force of stool, and at the same time, it does not adsorb substances that stimulate intestinal motility, and the spherical activated carbon provides moderate stimulation to the intestines, which has the combined effect of preventing constipation. It is also estimated that there is no gap.

Hereinafter, the present invention will be explained in detail with reference to examples, but the scope of the present invention is not limited to the equivalent examples.

Example-1 (Production of spherical activated carbon "I" Pitch obtained by 0'f:A decomposition of crude oil (softening point 175°C, nitrobenzene insoluble content 25%, l-1/C ratio 0.133) 750 Stir 1 part and 250 parts of naphthalene in a stainless steel autoclave.
Mix and dissolve at 70°C, and add "GOHSENOL GH-17" to this.
J (polyvinyl alcohol suspending agent manufactured by Nippon Gohsei) 0.
After adding 3,000 parts of a 5% aqueous solution and stirring vigorously at 130° C. for 60 minutes, the mixture was cooled to air temperature while stirring to obtain 19 true spherical particles. After most of the water was removed, the particles were immersed in 518 particles of methanol, shaken to extract and remove Bufculen, and then dried with ventilation.
300 at 25℃/11r while blowing air in the kiln
Warm to 7i+°C to form inaccessible spherical particles at 1 [Also. Then, the air supply was stopped and steam was supplied instead for 90 minutes.
It is carbonized by warming the stomach to 0℃, and further activated by keeping it at this temperature, producing highly spherical activated carbon with a particle size of 0.1 to 15 m (!7 I).

By changing the activation time, two types of spherical activated carbon with different degrees of activation were analyzed.

Comparative sample j ThlNo. 1 has a low activation degree, and comparative sample No. 002 has a high activation degree, and both have spherical beads prepared by sieving.

Next, a portion of each of the spherical activated carbons of Comparative Sample rA No. 1 and Comparative Sample No. 2 was added at a concentration of NH3 of 10 p.
The spherical activated carbon was immersed in an ammonia aqueous solution with a volume/weight ratio of 10 d/1 at room temperature for 3 hours. Next, take out the spherical activated carbon from the solution,
Drying at a temperature of 110° C. for 16 hours produced spherical activated carbon.

The product from activated carbon with a low degree of activation was sample No. 1.
Try products from activated carbon with a high degree of activation.
No, set as 2.

Table 1 shows the properties of these four activated carbons.

In addition, the adsorption ability was measured by an in vitro test for adsorption ability for creatinine and uric acid. 2 mentioned above
These substances are well known as harmful substances that are produced in the body due to metabolic disorders such as kidney disease.

Table 1 Characteristics of spherical activated carbon test v1 (Note) 4 = 1 The pore volume in the range of pore radius ioo to 75,000 pores was measured using a mercury intrusion porosimeter "Porosimetro Model 70" (manufactured by Carlo Erba, Italy).

*2 5 of the substrate at pH 7.4 in phosphate buffer
■/(Measured at a concentration of 1ρ.

*3 The pll of the spherical activated carbon was measured according to the 7J method described in the Japanese Pharmacopoeia Law (9th revision) "Medicinal Charcoal".

Samples V+ and 3 were immersed in 60 d of distilled water, boiled for 5 minutes, and then after cold fJI, 50 ml of distilled water, which had been reduced by evaporation, was added, and the pll of the liquid phase was measured.

The measured pll value is used as the pll value of Trial II.

All samples met the standards for purity test, drying range T, and ignition residue of "medicinal charcoal" under the Japanese Pharmacopoeia Act (9th revision).

(Acute toxicity test) An acute toxicity test was conducted using mice for the samples shown in Table 1.The results are shown below, and the spherical activated carbon of the present invention is extremely safe even when thrown in large quantities. It was confirmed that the value was high.

Commercially available ICR, -JCL female mice (body weight 22±1 g) were used as experimental animals, and the four samples shown in Table 1 were orally administered by force using a gastric probe. Litcl+ricld-14tlcoxo was determined by the determination of life and death after one week.
LDso was determined using the n method. The results are shown in Table 2.
After a week, it was resolved, but the appearance and internal organs were fixed! No noteworthy abnormal findings were found in the IQ test, nor were there any noteworthy symptoms of mediocrity.

Table 2 Acute Toxicity Test (Note) As it was experimentally extremely difficult to administer doses of 9 or more to 15,0OOfn9/, the test was discontinued at the end of this administration. There were no deaths of mice after administration of 1500011 tg/KFI.

Actual flow example-2 (animal experiment) Wistar (body ffl 130-140t)
Bentoparvital-Na was orally administered in the form of an aqueous solution to 2 oIyJ/9 body weight using a series II rat 1-.

Immediately, the samples shown in Table 1 were suspended in water for 20 minutes.
0#l! The animals were orally administered to achieve a body weight of J/kg. At the same time, a comparative test was conducted in which activated charcoal was not administered. Ten specimens were used for each activated carbon sample administration group and non-administration group.

Next, the average maximum moisture content of bendoparbital 1'Ja in the blood was determined, and the ratio to the concentration in the comparison test group was expressed as the removal rate.The results are shown in Table 3.

As is clear from Table 3, detoxification effects were observed in all groups administered with the spherical activated carbon samples. However, Samples No. 1 and No. 2 (treated with ammonia) have particularly high detoxification effects compared to comparative samples Ilo, 1 and No. 2 (not treated with ammonia). Ta.

Then, 90 minutes after administration of activated charcoal, these specimens I!
Anesthetize Y! The enzymatic tube was removed and the degree of intestinal transport of activated charcoal was compared. That is, the ratio of the transfer distance ρR1 from Naruto to the terminal end of the rectum to the activated carbon reach point was determined as the transfer rate. As shown in Table 4, the results show that in sample 8Y using the activated carbon sample of the present invention shown in Table 1, the transfer rate of A was large and the Ina effect was small.

Table 4: Intestinal transport rate of activated carbon sample In order to examine the actual adsorption capacity of the spherical activated carbon of the present invention, the following experiment was conducted in the presence of sodium stearate, which prevents the activated carbon from adsorbing harmful substances in the intestine.

II C3j of sodium stearate in the intestine in phosphate buffer of pl+ 7.4
Creatinine was further dissolved in the above solution to a concentration of 15 ate/dρ. Each sample from Table 1 was then added to the above solution and shaken for 3 hours, after which the mixture was divided into 5 ml portions.

10 of aluminum sulfate to precipitate the stearic acid.
% aqueous solution was added to the 3W4 mixture, and the concentration of creatinine in the surface layer was measured by the colorimetric window 4 method.

All experiments were conducted at a temperature of 37° C. except for the measurement step using the colorimetric interleaving method.

The measurement results are shown in Table 5.

As is clear from Table 5, the spherical activated carbon of the present invention has a similar adsorption capacity compared to the comparative sample (not treated with ammonia). As a result, the spherical activated carbon of the present invention has an absorption capacity of 1.9% for harmful substances such as creatinine in the presence of substances such as sodium stearate that prevent activated carbon from adsorbing harmful substances in the intestine.
It is clear that

Claims (1)

[Claims] (1) At least 85% of the spherical activated carbon is a true sphere,
The ratio of the maximum diameter to the minimum diameter of the particles is 1.0 to 1.3, and the diameter is 0.
05~2.0mm, surface area 500~2000m^2/g
, the pore volume at a pore radius of 100 to 75,000 Å is 0.
05-1.0ml/g, pH=6-8,
Ammoniated oral antidote.