KR810000112B1 - Electric dust collecting device - Google Patents

Abstract

Al7(OH)17(SO4)2.12H2O(I) had a high phosphate-binding capacity and was useful for diminishing phosphate resorption in the digestive tract for treatment of phosphate-contg. urinary calculi without raising the pH of the stomach contents or urine. In subjects receiving 4x2 g I/day orally, the urinary phosphate excretion decreased from 17.68 to 4.34 m mole/hr without significantly altering the urine pH or Ca excretion. Tablets were prepd. from a mixt. of I 400, lactose 100, starch 85, poly(vinylphrrolidine) 10, and Mg stearate 5 kg.

Description

Method for producing a novel aluminum compound

The present invention relates to a method for producing a novel aluminum polyhydroxy sulfate hydrate having the following structural formula.

Al ₇ (OH) ₁₇ (SO ₄ ) ₂ n (H ₂ O) (n = 10-15, suitably 12)

Since urea stones are formed through a very complex process, his treatment is very difficult. In the past, insoluble aluminum compounds, especially aluminum hydroxide gels, have been reported in patients with phosphate stones that have not been shown to have significant results (see below).

1) E. HIENZSCH u. H. J. Schneider, Der Harnstein, Gustav Fischer Verlag Jena, 1973

2) E SHORR u. A. C. Carter, J.A.M.A., 144, 1549-56 (1950)

3) H. KRACHT, A.A. KOLLWITZ, E. LOHE, Der Urologe, S. 16 (1970)

4) TH. FRIIS u. E. WEEKE, Acta Med. Scand., Vol. 187, 41-48 (1970)]

5) H. STUDER, Helv. Chirurgica [Acta, 23, 130 (1956)]

6) E. SHORR, Journ. Urolog., 53, 507- (1945)

7) L. S. GOODMAN u.A. GILMAN, The Pharmacological Basis of Therapeutics (4th Edition)

8) M LOTZ et al, New Engl. J. Med. 409-415 (1968)

9) Dos 1 921 999, 2 152 228, 2 201 752, 2 406 120

The action of these compounds is due to a decrease in phosphate absorption from food. Because, when oral administration of aluminum hydroxide gel or aluminum carbonate gel, phosphate adducts are formed in the intestine and excreted into feces. The disadvantage of these compounds is that the aluminum compounds are unstable and the phosphate-binding capacity of the aluminum compounds is insufficient. For this reason, high doses cause disturbances in the gastrointestinal tract, and in most cases unnecessarily bind acids in the stomach. It is difficult to control these compounds because of their low phosphate-binding capacity, and if administered in large amounts, it may occur that the phosphate is completely removed from the food the patient eats. Small amounts of phosphate are necessary to balance the metabolism in vivo. Agents containing these compounds are mainly used in the form of gels or emulsifiers, which require the patient to carry the medicine and take a significant amount. In the case of a dried product, the patient should take a larger number of stagnation than the patient can tolerate. Moreover, most of the aluminum compounds currently in use undesirably raise the pH of the urine, causing the phosphate to become supersaturated, thereby enhancing the tendency for the substrate in the urine to crystallize.

In view of this fact, it has a phosphate-binding capacity several times higher than conventionally known compounds, is a dried form that is easy to handle and suitable for small dose administration, with little change in pH in the stomach, and There is a need to prepare aluminum compounds that do not significantly increase the pH and that do not change their activity due to aging.

It was found that aluminum polyhydroxy sulfate hydrate, a novel compound of the following structural formula, satisfies the above conditions:

Al ₇ (OH) ₁₇ (SO ₄ ) ₂ nH ₂ O, where n is 10 to 15, more preferably 12

The compound is well suited for treating phosphate stones in the urethra by preventing the growth of stones and indirectly dissolving or removing the stones.

This novel aluminum polyhydroxy sulfate is prepared by the following procedure: aluminum sulfate and sodium bicarbonate in an aqueous solution are stirred at a molar ratio of 1: 5 and a volume ratio of 3: 5 by simultaneous reaction at room temperature (concentration of the solution is hydrogen carbonate). Up to the solubility of sodium) and at the same time the pH in the reaction mixture is kept constant at 5-6. The solution is mixed with water at the same time. (No reaction product is obtained with satisfactory phosphate binding capacity unless proportional to the molar ratio and pH are set)

Aluminum polysulfate precipitates as an amorphous white powder, which is washed with water until the sulfate is freed and then dried at 1-2 mmHg vacuum at 50 ° C. Insoluble aluminum polyhydroxy sulfate is free of carbonate and undergoes weak acid reaction in an aqueous suspension. The phosphate-binding capacity of this compound amounts to 260-300 mg of PO ₄ per gram of dry matter. Even after long-term storage under normal conditions, this value does not change. The novel aluminum polyhydroxy sulfate is a complex of seven atoms and has a phosphate binding capacity ten times stronger than conventional aluminum oxide, aluminum hydroxide and aluminum hydroxide gel, and twice as strong as aluminum carbonate.

An important factor in determining the phosphate-binding capacity of this novel aluminum polyhydroxy sulfate compound is the degree of hydration. The degree of hydration is more than 10 water molecules per molecule and 12 bonds proved to be very advantageous for binding phosphates. If the number of bonds per molecule is less than 10, the phosphate binding capacity decreases.

The compounds of the present invention, which are of the following structural formula, have therapeutically valuable properties.

Al ₇ (OH) ₁₇ (SO ₄ ) ₂ nH ₂ O (n = 10-15, suitably 12)

When administered to a patient with phosphate stones, a surprising protective action and dissolution of the stone appear.

As shown in in vitro and clinical trials of the phosphate-binding ability of the compounds, it has been found that the novel aluminum polyhydroxy sulfate compounds are much superior to conventional aluminum, compounds. The experiments were conducted at room temperature several times under conditions of complete biobalance (standard nutrition, calories needed per day, carbohydrates, proteins and fats as human criteria). After oral administration of 2 g of aluminum polysulfate hydrate four times a day, a urine sample was collected and analyzed 24 hours after a suitable time. Adjust the intake of phosphate and nitrogen.

To the purpose of the treatment is reduced to phosphate ^{uptake, [Ca -] · [PO4} -] , the amount of phosphate required for metabolism is used, whereas increased soluble product. Regardless of the general metabolic needs, a therapeutic effect can be achieved by using 0.8 to 2 g of phosphorus per day, ie, 2.4 to 6.1 g of phosphate.

Since phosphate solubility depends on the pH in the urine, the pH value should not change significantly.

In clinical trials were performed as follows: Aluminum polyhydroxy-sulfate was administered after 7 days. Factors influencing the results, such as the duration of the experiment, experimental data, and experimental materials, were first reviewed by various analytical methods. The results were surprisingly satisfactory.

1.Aluminum polyhydroxy sulfate hydrate does not increase the pH in urine very much, and in contrast to the conventional formulations used as modulators in this clinical study, it exhibits an average increase in pH of 6.28 to 6.39, which has a mean pH increase of 6.28 to 6. It was 6.63. This is important because pH is the decisive factor in dissolving phosphate stones. Calcium phosphate salts are supersaturated twice in urine at pH 6.0, whereas they are 8 times supersaturated at pH 7. This phenomenon is considered to indicate that urine is a special solvent system for supersaturation. Whatever medication you use to treat stones, you should not raise your urine pH. This is because the change in pH in urine has a significant effect on the solubility of phosphate in urine. These conditions are satisfied by the aluminum polyhydroxy sulfate hydrate of the present invention.

2. The urine phosphate component is reduced to an amount of 17.68 to 4.34 mmol / 24 hours. This fact is that the phosphate binding action of the cited therapeutics can achieve the desired metabolic effect in the apparatus.

3. The amount of calcium excreted in urine for 24 hours is approximately the same in both test periods (initial and dosing periods) (average of 4.80 mmoles per day initially and 5.07 mmols per day). This fact is attracting calcium balance.

4. Another advantage over aluminum polyhydroxy sulfate hydrate is that the overall compatibility is good. In this clinical trial, a large dose of 2g, 4 times a day, was acceptable. This fact is advantageous because the new drug can be suspended in solution or taken with liquid growth.

Another evidence of good compatibility is that it does not significantly change acidity, even when excreted.

As shown in the following experiments, excellent compatibility is confirmed through experiments on toxicity.

Wistar rats were starved for 20 hours before administration of the substance. The material suspended in 1% rubbery tragacanth solution was administered via gavage. Four groups of ten (five male and five female) mice, respectively, were administered 100, 1000, 2000 and 4000 mg / kg. Observations were made over 14 days during normal feeding of rats. Health status, weight and body temperature were recorded daily.

We also tested dogs. The present compound suspended in tap water was administered to the stomach using a funnel and gavage. When tested for the first time with tap water, there was no nausea. The amount administered to the first group (12 dogs) was 1 g / kg body weight. After seven days the dogs were fed normal and their general health was recorded. Eight days after the minimum dose of medication, six dogs were divided into two groups. At this time, the weight was administered at 2.5 and 5g / kg and observed continuously for 7 days. Body weight and body temperature were normal in these two experiments, with no toxicity in rats and dogs.

EXAMPLE

[Production of Compound]

A solution of 84 kg of sodium hydrogen carbonate dissolved in 1000 l of water and 133 kg of aluminum sulfate 18H ₂ O in 600 l of water was added to the vessel containing 600 l of water over 60 minutes with vigorous stirring at room temperature. pH was adjusted to 5-6. The reaction solution was stirred for an additional hour and then the pH was 5.4. The precipitated product was separated by centrifugation and then washed with water until the sulfate was liberated and vacuum dried at 50 ° C. for 20 hours.

The structure of this compound was as follows.

Al ₇ (OH) ₁₇ (SO ₄ ) ₁₂ H ₂ O

The phosphate-binding capacity was 260-300 mg / g per g dry matter.

The degree of hydration was adjusted based on the control measurements while the material was drying. The number of bonds per molecule was not reduced to below 10. The number of binding water should not be more than 15 because it is not preferable for the herbal dry preparation, although it does not affect the phosphate-binding capacity of the desiccant.

When the chemical analysis to determine the properties of the compound, an anhydride was obtained as follows.

Al ₇ (OH) ₁₇ (SO ₄ ) ₂

Moisture of the prepared material was measured 12H ₂ O per molecule, that is, the structural formula is as follows.

_{Al 7 (OH) 17 (SO} 4) 2 · 12H 2 O

Example 1 for Preparation

[Powder system]

100 kg of powder was prepared with the following composition:

Example 2 for Preparation

[refine]

600 kg of compression compositions were prepared with the following composition:

Example 3 for Preparation

100 kg of gel was prepared with the following composition:

[Gel]

Claims (1)

In the aqueous solution, aluminum sulfate and sodium hydrogen carbonate were added in a molar ratio of 1: 5 and in a volume ratio of 3: 5 by stirring at room temperature while maintaining the pH at 5-6, and adding water to the resulting solution, followed by precipitation. The product was washed until the sulfate was freed and then dried in a vacuum at 1 to 2 mmHg and at 50 ° C. to give the structural formula [Al ₇ (OH) ₁₇ (SO ₄ ) ₂ nH ₂ O]] (n is from 10 to 15). Im) aluminum polyhydroxysulfate hydrate.