JPS6010039B2 - Method for producing new pharmaceutical compounds - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a novel compound containing an organic anion for use as a central nervous system drug, and more particularly, the present invention relates to a method for producing a novel compound containing an organic anion for use as a central nervous system drug, and more particularly, the present invention relates to a method for producing a novel compound containing an organic anion for central nervous system medicine.
s), anti-rheumatic agents (AMrhe tics), and anti-inflammatory agents (AMrhe tics),
The present invention relates to a method for producing a novel rust compound useful as a rust compound.

According to the present invention, the following general formula MgXAly(OH)2. 13y-Z(A)2・aRO
H・・・・・・・・・[In formula 11, A is (i)
In the formula, R is an anion of a compound that is a hydroxyl group, an acyloxy group, a 3-trifluoromethyl phenylamino group, or a 2,3-dimethylphenylamino group, (o- In the formula, R2 is a hydrogen atom or The anion of a compound that is a methyl group, the anion of p-(di-n-propylsulfanyl) monobenzoic acid, the anion of 91-(p-chlorobenzoyl)-5-methoxy-2-methyllindole-3-monoacetic acid anion, (ii) an anion of 2-phenyl-4-carboxyquinoline, or an anion of N sulpyrine;
A combination with a carbonate ion or a sulfate ion, R is a hydrogen atom or an ethyl group, and x, y, z and a are represented by formula 1
/4 Mi x/y Mi 8 1/2 blowing Mi 1 〇. 2 is a positive number that satisfies
6～21.02 1003.93～
9.40 402.61~ 6.41
202.34
212.00 22
1.76 41.66
4 1.53 9 1.50 Same as 11 x-
A compound having a line diffraction pattern is provided.

Conventionally, many organic compounds having a carboxyl group, phenolic hydroxyl group, or sulfonic acid group as a functional group are already known as central nervous system medicines, particularly as antipyretic, analgesic, antirheumatic, and antiinflammatory agents.

These pharmaceuticals are often administered orally to patients. Among these drugs, the drug name, chemical formula or chemical name, dosage,
Indications, side effects, and contraindications are shown in Table 1 below. The present inventors succeeded in synthesizing a novel rust compound containing as an active ingredient an anion of a central nervous system drug as shown in Table 1 above.

The novel anchor compound of the present invention is a compound having a composition represented by the above general formula {11 and a layered crystal structure shown in the above-mentioned X-ray diffraction image.

In the present invention, the basic Suzu compound has the general formula Mg6
Mountain 2 (OH), 6・An・a′ROH….・・・．・．． {
2-wherein A and R have the meanings given above, n is 2 when A is a monovalent anion, 1 when A is a divalent anion, and a' is 2.5 It is a number from 6 to 6.

Conventionally, as a compound having a similar composition and similar crystal structure to the compound represented by the above-mentioned formula {2-, the formula Mg6
Mountain 2 (OH), 6・C03・4L0・・・・・・・・・
[3: Hyde represented by .

Talcite is known, and the novel complex compound of the present invention is
It can be considered that the carbonate ion of hydrotalcite is a compound substituted with a specific organic anion. However, it must be noted that the novel tsuba compound of the present invention cannot be synthesized by a method of ion-exchanging the carbonate ion of hydrotalcite with an organic anion. In the novel tsuba compound of the present invention, all of the monovalent or divalent anions A are preferably anions of the above-mentioned active ingredients {i} to N, but up to 50 mol% of the anion A within the range of halogen ion, e.g. CI
-, Br-, 1-, nitrate ion, carbonate ion, or sulfate ion.

In the general formula {1, when y is 2, x is 3 to 1
0, and z is 1.5 when A is a monovalent anion.
When A is a divalent anion, it is preferably a number from 0.75 to 1.25, and a is preferably a number from 2.5 to 6. The novel compound of the present invention has the following characteristics.

In the tsuba compound of the present invention, hawk crystals of Mg and N are formed within a certain range of Mg and AI, that is, within a range of 1/4 × x/y × 8.

This can be seen by synthesizing the compounds of the present invention with various ratios of Mg and AI and analyzing the obtained products by powder X-ray diffraction method. There is a proportional relationship between the molar ratio and Vegard's law.
It is understood by following.

Vegard separation means that when A and B form a mixed crystal, d=k
, d, and 10 k2 also mean that the following relationship holds true: d: lattice constant k, , k2: constant d, , also: lattice constant specific to A and B).

The compound of the present invention is a crystalline substance with a layered structure, and the refractive index of the compound is in the range of 1.4 to 1.7 regardless of the composition.

In addition, it is insoluble in water and organic solvents, usually begins to dissolve at the 4th position in acids, and is in principle immovable in alkalis, but begins to dissolve when the pH becomes 13 or higher. This property of being insoluble in alkaline water is one of the remarkable features of the compound of the present invention, as well as the fact that the resulting compound contains a small amount of alkali (0.01 to 0.001%). The crystal size of the compound of the present invention is usually 60 to 2
The crystal size is distributed between 00A and 00A, but the size of this crystal can be freely increased by hydrothermal treatment.

The crystal structure is Mg(OH)2 or Mg(OH)2 and A
It consists of a layer consisting of all bonds of I(OH)3 and an intermediate layer consisting of coordinating anions and water or ethanol molecules, and both Mg(OH)2 and mountain (OH)3 are 6
It forms an octahedral layer of coordination, forming a lotus shape. A coordinating anion A exists almost perpendicularly to this octahedral layer, and connects the two octahedral layers.

Therefore, the size of the interlayer changes corresponding to the size of the ligand, and the amount of interlayer crystallization water also changes. In principle, whenever the size of the intermediate layer formed by the coordinating anions increases by n times of about 3.2 A, the interlayer water of crystallization also increases by n times. The compound of the present invention forms a layered crystal structure, resulting in Mg(OH
)2, AI(OH)3 and A are about 100° C. more stable to heat than either of them alone.

The compound of the present invention can be easily distinguished from other compounds and identified by powder X-ray diffraction.

Powder X-ray diffraction images of the compounds of the present invention are shown in Table 1. Table 1 X-ray diffraction measurement conditions for compounds of the present invention: ○U-Ko ray, Ni filter --Note: dA0
......Face spacing 1/lo...hk
l... Miller index... Relative strength Z As shown in Table 1, the lattice constant in the C-axis direction expands and contracts depending on the size of the coordinating anion A, but in other directions The lattice constant is negligible compared to that in the C-axis direction.

The novel tsuba compound of the present invention is produced by the following method.

That is, according to the present invention, the following general formula MgXA1y(OH)2X+3y-Z・AZ・aH20
In the method for producing a compound in which x, y, z, A and a have the above-mentioned meanings, or a compound (ii) which is a monovalent inorganic anion such as a nitrate radical; or a compound (ii) of the formula NY3...'7} in which Y is a halogen atom, a monovalent anion such as a nitrate radical, or a lower alkoxy group; Aluminate alkali metal salt and {iii) Formula: In the formula, M is a hydrogen atom or an alkali metal, and A is a compound having the above-mentioned meaning. A method is provided which consists of reacting under water or in a lower alcohol.

As the compound of formula '6}, magnesium chloride, magnesium bromide, magnesium iodide, and magnesium nitrate can be used.

Further, as the compound of formula '7', aluminum chloride, aluminum bromide, aluminum nitrate, aluminum ethoxide, and aluminum isopropoxide can be used. Further, as the aluminum raw material, alkali metal aluminates such as potassium aluminate and sodium aluminate may be used. At this time, the above formula {
In the compound No. 11, when carbonate ion or sulfate ion is introduced in an amount of 50 mol% or less of anion A,
Magnesium salts such as magnesium nitrate, basic magnesium carbonate, or aluminum sulfate, such as AI(O
H) 3.N may also be used in combination with an alkali carbonate such as C03 and an aluminum hydroxide complex with the above-mentioned magnesium raw material or aluminum raw material.

In the present invention, as the compound of the formula (1), for example, the compounds shown in Table 1 above can be used as is) or in the form of an alkali metal salt.

Of course, instead of separately using the magnesium compound of the formula [6} and the organic compound of the formula {81], the magnesium salt of the organic anion A can be used as a raw material, but in this case, the magnesium salt of the organic anion A can be used as a raw material. It is necessary that the magnesium salt be sufficiently dissolved in the reaction medium. It is important that the reaction in the present invention is carried out in water or a lower alcohol such as ethanol, and at a pH of 8 or higher, preferably 9 or higher.

These solvents are selected in consideration of the solubility of the raw materials in them. That is, it is preferable to select a solvent in which the raw material has a high solubility.

In order to bring the pH to the above conditions, an alkali metal hydroxide or ammonia (or ammonium hydroxide) is added to the reaction system as an OH source. When carrying out the method of the present invention, it is important to carry out the reaction under conditions where carbonate ions are not substantially present in the reaction system.

This is because, when carbonate ions are present in the reaction system, carbonate ions are preferentially incorporated into the crystal structure compared to organic anions. For this reason, when carrying out the method of the present invention, it is necessary to take precautions such as using decarbonated water and purging the inside of the reaction vessel with nitrogen. For similar reasons, it is necessary to avoid contamination of other divalent inorganic ions, such as sulfate ions, into the reaction system. However, in the case of introducing carbonate ions or sulfate ions in an amount of 50 mol% or less of the anion A in the compound of formula [1'], carbonate ions or sulfate ions in the above range are present in the reaction system. Of course this is acceptable. There are no particular restrictions on the proportion of raw materials used, but
It is preferable to use the magnesium raw material and the aluminum raw material at a ratio such that 300 y moles of AI per 200 mol Mg are used. The organic anion A is preferably present in a proportion of at least z moles per 30 y moles of needles. Other reaction conditions are not particularly limited, and the reaction can be carried out, for example, at room temperature to 100°C and under pressure from normal pressure to about 10 atmospheres.

In the present invention, in the case of an organic compound having both a carboxyl group and a phenolic hydroxyl group, such as salicylic acid, a pH lower than pH 13.7, for example, pH 1
O acts as a monovalent anion, while at a pH of 13.7 or higher, it acts as a divalent anion.

Thus, according to the invention, salicylic acid can be incorporated into the crystal structure as a monovalent anion or as a divalent anion.

According to the present invention, the compound of formula '11 is produced as a precipitate by carrying out the reaction under such conditions.

Therefore, the target compound can be obtained by recovering the obtained compound by any solid-liquid separation operation, and optionally washing with water and drying. The novel Suzu compound obtained by the method of the present invention can be subjected to various post-treatments if necessary.

For example, in order to further improve the crystallinity of the obtained compound,
This compound can be hydrothermally treated in water at a temperature of 10 to 150°C, if necessary under pressure. Further, when the obtained compound contains a monovalent inorganic anion, such as a halogen ion or a nitrate ion, the resulting compound is brought into contact with an aqueous solution of the compound of the formula [8}, An inorganic monovalent anion can be ion-exchanged with an organic anion.

This ion exchange process involves packing the product compounds into a column and
This can be carried out by introducing the aqueous solution into this column or by suspending the product compound in the aqueous solution. The novel key compounds of the present invention are useful as central nervous system medicines, particularly as antipyretic, analgesic, antirheumatic, and antiinflammatory agents, and are administered orally to patients.

The dosage of the above compound may be such that the active ingredient, ie the organic anion, in the compound is in a conventionally used dosage, for example the dosage shown in Table 1. For example, some examples of dosages of the novel compounds of the present invention are shown in Table 2 below. Table 2 In the new parent complex compound of the present invention, the organic anion, which is an active ingredient as a medicine, is incorporated into the layered crystal structure and is stable.

That is, in the new parent complex compound of the present invention, although the active ingredient is reacted with the magnesium component and the aluminum component, the active ingredient is incorporated into the crystal structure in the form of an anion as is. ing. This fact, for example, as shown in FIG.
I2(OH),. 3 (indometacin-1),. 5 (N
03-)o,.・2. This can be easily understood from the fact that the infrared absorption spectrum of the organic matter obtained by decomposing the compound (20) with dilute hydrochloric acid (IN) and then extracting with chloroform almost completely matches the infrared absorption spectrum of indomethacin. It is possible. Furthermore, the novel compound of the present invention has a stable layered crystal structure and is therefore thermally and chemically stable.

For example, the novel complex compound of the present invention decomposes at 42,000°C, and compared to the decomposition humidity of salicylic acid of 200°C.
Decomposition temperature is extremely high.

Furthermore, the novel tsuba compounds of the present invention are extremely stable against ultraviolet light. In addition, the novel rust compound of the present invention
It is generally white and odorless, making it eminently suitable for oral administration.

For example, it is understood that the compound of Example 3 is tasteless and odorless, making it more suitable for oral administration, whereas the corresponding ibufenac has a pungent odor. The novel rust compound of the present invention has the remarkable property of having both the above-described action as an analgesic/antipyretic agent or anti-inflammatory agent and as an antacid.

For example, Tsuba compound 3 of Example 4. The Fuchs curve when [Group 20] is added to the artificial gastric juice is as shown in Figure 4, and according to this, the novel tsuba compound of the present invention has a fast-acting, maximum (m
It will be understood that it has performance as an antacid with excellent pH and durability.

Furthermore, the new parent complex compound of the present invention itself has excellent tableting properties, and this fact will be easily understood by referring to Table 3 below. The invention is illustrated in the following examples.

Example 1 Magnesium nitrate 0.8M/Aluminum nitrate 0
．． 2M/mixed aqueous solution thereof, 0.0 of salicylsalicylic acid
9 M/alcohol solution and sodium hydroxide 0.5
M/Make a 50% alcohol solution.

These three liquids were placed in a reaction tank with an overflow device with a capacity of 0.6 m, and a mixed solution of magnesium nitrate and aluminum nitrate was added at 3.2 m/m.
In, the salicylsalicylic acid alcohol solution is added at a rate of 19.4 min/min, and the sodium hydroxide 50% alcohol solution is regulated at a flow rate of about 12 min. In addition, the reaction tank was filled with 20 volumes of 50% alcohol solution in advance, and the pH of the reaction solution was adjusted to 10 while stirring.
．． Sodium hydroxide 5 to maintain between 0 and 10.5
Adjust the flow rate of 0% alcohol solution.

Discard the overflow during one hour after the start of the reaction, and collect the reaction suspension thereafter.

The reaction is carried out in a nitrogen gas stream. Dehydrate the reaction suspension;
After washing, the product is dried at 70°C.

Chemical composition X-ray diffraction dA=8.23 4.12 2.70 Example 2 Using decarboxylated water, 2 molar NaOH aqueous solution and NC13/Fine 204. Total, M and 1218LO12. An aqueous solution dissolved in water with 200 skin after, and quinophene (
chi dish phen skin m)7. acid to 100 [0. Mark N
Make an aqueous solution dissolved in aOH aqueous solution.

Put chinophene (chinophemmm) NaOH aqueous solution into a Type 4 round bottom flask and adjust the pH.
Dip the electrode into this and connect the electrode to a pH meter.

The CO in the air enters the flask through the decarboxylated air.
2 While preventing the mixture of gases, the liquid temperature is 260 while lighting the lamp.
While maintaining the pH of the reaction solution, both of the solutions are added dropwise from a burette, and the amounts of both solutions are adjusted so that the pH of the reaction solution is maintained at 10.0 to 10.5. After the addition was completed and the reaction suspension was allowed to simmer for about 1 minute, the reaction suspension was taken out, dehydrated under reduced pressure, washed with 200ml of ion-exchanged water, and dried in a ventilation dryer at 75°C for 1 hour. After drying, use it as a product.

Chemical composition X-ray diffraction dA 8.31 4.17 2.67 Example 3
Using decarboxylated water, 2 mol of NaOH/aqueous solution, and NC13/porridge 204. Total, M&121 spots 3012. An aqueous solution prepared by dissolving foundation in 200 ml of water, and ibufenac (
p-isobutyl phenylacetic acid)5. Ethyl with 100 foundations.

Make an aqueous solution in alcohol. A lbMenac alcohol solution is placed in a round-bottomed flask, and the electrode is immersed in it, and the electrode is connected to a pH meter.

The CO in the air enters the flask through the decarboxylated air.
2 While preventing the mixture of gases, lower the liquid temperature to 25o
While maintaining the pH of the reaction solution at 10.0 to 10.5, both of the solutions are added dropwise from a burette, and the amounts of the two solutions added are adjusted so that the pH of the reaction solution is maintained at 10.0 to 10.5.

After the dropwise addition was completed and the mixture was stirred for about 1 minute, the reaction suspension was taken out, dehydrated under reduced pressure, the reactant was washed with 200ml of ion-exchanged water, and dried in a ventilation dryer for 750 minutes for 1 hour. After that, it is made into a product.

Chemical composition X-ray diffraction 8.18 4.08 2.70 Example 4 Using decarboxylated water, NaOH 2 mol/aqueous solution and MCI3 fine 204. Chicks, M&1218LO12. An aqueous solution of Shigeru dissolved in 200 ships of water, and sodium salicylate2. Make an aqueous solution by dissolving 100% of tether in water.

A sodium salicylate aqueous solution is placed in a Class 4 round-bottomed flask, and a pH electrode is immersed in the solution, and the electrode is connected to a pH meter. While pouring decarbonated air into the flask to prevent CO2 gas from entering the flask, the liquid temperature was increased to 2.
While maintaining a pH of 5.0 to 0.0, both of the above solutions were added dropwise from a burette, and the amounts of both solutions added were adjusted so that the pH of the reaction solution was maintained at 13 or higher.

After the addition was completed and the mixture was allowed to stand for about 10 minutes, the reaction suspension was taken out, dehydrated under reduced pressure, and diluted with a 3% aqueous solution of sodium salicylate.
After pouring 100ml of ion-exchanged water, the reaction product was purified with 100ml of ion-exchanged water and dried in a ventilation dryer at 15°C for 1 hour to obtain a product.

X-ray diffraction 7.96 3.93 2.61 The x-line diffraction diagram of this compound is shown in Figure 1, and its differential thermal analysis curve (solid line, integral curve; dotted line, differential curve) is shown in Figure 2.
Further, their infrared absorption spectra are shown in FIG. 3, respectively.

Furthermore, the antacid properties of this compound were evaluated by Fuches
) is shown in Figure 4 as a curve.

Incidentally, this measurement was carried out according to the Fuchs modified method described below. The following artificial gastric fluid will be used in the test.

Common salt (high purity) 2.0g Rare Hydrochloric acid 24.0Kite - Distilled water Total remaining amount 1000 (0.068N) Magnetic stirrer, 37. In a 500' beaker with a thermostat maintained at 150
After filling with artificial gastric juice and inserting the boat meter's electrodes and thermometer, the contents are stirred using a magnetic stirrer.

When the temperature reaches 37.5° C., add 1 gram of sample and simultaneously record the change in pH on the chart. After 1 minute has passed, activate the regular pump to remove gastric juice for 2 minutes.
Add at a rate of 1 minute.

The following antacid properties can be obtained from the chart in FIG.

Rise time (time required for gastric juice to reach pH 31...
・−． ...1-・---------------
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐”‐‐‐‐17 Maximum pH・・・・・・・・・・・・・・・・・・・・・・・・・・・
……． ... Duration (time until the pH of gastric juice drops below 3). ...1...・．．・■■．・・・．・・■．・
・・・・・・■．・．．・■．・・■・■■Acid reaction rate・・・・
・・・・・・・・・・・・・…．・．． ．．・．． ．．・．． ．．・・・・・・・
……． ．． - From the above results, it is understood that the compound according to this example has rapid and long-lasting effects, and has excellent antacid properties.

Example 5 Using decarboxylated water, NaOH 2 mol/aqueous solution and AIC13/mother L0 4. Hina, MgC12・8LO1
2. 4. An aqueous solution of the latter dissolved in 200 g of water, and sodium salicylate. Make an aqueous solution by dissolving the chicks in 10o water.

A sodium salicylate aqueous solution is placed in a four-frame round-bottomed flask, and a wind electrode is immersed in the solution, and the electrode is connected to a pH meter.

The CO in the air enters the flask through the decarboxylated air.
2 While preventing the mixture of gases, reduce the liquid temperature to 25q while lighting the lamp.
While maintaining the pH of the reaction solution, both of the solutions are added dropwise from a burette, and the amounts of both solutions added are adjusted so that the pH of the reaction solution is maintained at 10.0 to 10.5.

After the dropwise addition was completed and the mixture was allowed to stand for about 10 minutes, the reaction suspension was taken out, dehydrated under reduced pressure, the reactant was thoroughly washed with 70ml of ion-exchanged water, and 200ml of 3% sodium salicylate aqueous solution was added. After washing with water and drying in a ventilation dryer for 75 qo and 1 hour, the product is prepared.

Chemical composition X-ray diffraction 154 7.19 5.30 3.97 Examples
Using 675% ethanol and isopropanol,
Prepare 0.8 M/Z of magnesium nitrate, 200 ml of a 0.2 M/mixed solution of aluminum isopropoxide, and 400 ml of a 0.2 M/Z solution of indomethacin.

1. Pour an ethanol solution of indomethacin into a four-necked flask, dip a pH electrode into it, and stir using a magnetic stirrer.

The mixed solution and ammonia gas are added and adjusted to maintain pH 8.0±0.5 under normal temperature and pressure. After the reaction is completed, the resulting reaction suspension is filtered under reduced pressure, washed with ethanol, then washed with ion-exchanged water, and dried at 700 ml to give a product. This product suppresses gastric disorder, which is a side effect of indomethacin (an anti-inflammatory drug), and
It has excellent anti-inflammatory effects that are effective in small amounts. Incidentally, the reaction and other steps were performed in an N2 gas atmosphere. Chemical composition X-ray diffraction dA = 8.66 4.32 2.88 Figure 5 shows the infrared absorption spectrum A of the extract obtained by decomposing the compound of this example with IN dilute hydrochloric acid and then extracting with chloroform. and shows infrared absorption spectrum B of indomethacin.

Example 7 Magnesium nitrate 0.8 M/so, aluminum nitrate 0.1 M/mixed aqueous solution thereof, flufenamic acid 0.1 M
/Aqueous solution (flufenamic acid is dissolved in water by adding a dilute aqueous solution of sodium hydroxide.

) and sodium hydroxide in water.
These three liquids were transferred to a reaction tank with a capacity of 0.6〆 and equipped with an overflow device.
Use a metering pump to regulate the flow rate of the spirit and mountain salt mixture at 3.2 min/mjn, the flufenamic acid aqueous solution at 9.7 min/min, and the sodium hydroxide* aqueous solution at 10.3 min/min. Add. In addition, the reaction tank was filled with 200 [mu] of water in advance, and was flown to the ocean at 36 p.m. using a constant-speed taka-azusa machine to adjust the pH.
Keep the electrode immersed in the reaction solution at a constant temperature of 10.0 to 10.
．． Adjust the flow rate of the aqueous sodium hydroxide solution to maintain 5. The reaction was carried out for 4 hours, and the liquid that overflowed within 1 hour from the start of the reaction was discarded.The reaction suspension was then stabilized and the reaction suspension sampled in a container was dehydrated under reduced pressure. After washing with water, the product is dried at 70°C. This product suppresses gastric disorders that are a side effect of flufenamic acid (an anti-inflammatory drug), and has excellent anti-inflammatory effects that are effective in reducing symptoms. The reaction was carried out in a decarboxylation atmosphere.Chemical composition
Linear diffraction dA=7.62 4.07 2.59 The X-ray diffraction image of the compound of this example is shown in Figure 6, its infrared absorption spectrum is shown in Figure 7, and its differential thermal analysis curve is shown in Figure 8. They are shown in the figure (the solid line is an integral curve and the dotted line is a differential curve).

Example 8 0.8M of magnesium chloride using deionized water
200 0.2M/mixed aqueous solution of sodium aluminate and ibuprofen (p-lso-bum)
hydratropic acid) 0.4M/50
125% ethyl alcohol solution and 2M/sodium hydroxide aqueous solution were mixed with a magnetic stirrer and placed in a beaker with a pH electrode immersed in it.
Add it dropwise from a book buret and adjust the pH to 10.0-10.5.
react while maintaining the

The reaction is carried out in a nitrogen gas stream. After the reaction, the resulting precipitate was passed through a furnace under reduced pressure, washed with ion-exchanged water, and heated to 80 oo
Dry with. Chemical composition X-ray diffraction 8.12 4.06 2.69 The properties of the compounds obtained in each of the above examples as excipients are compared with those of conventional excipients as shown in Table 3 below.

The properties as an excipient were determined by measuring the compressive strength (Kg/kg) of tablets compressed at various compression pressures using a Strong Cobb hardness tester. According to the results, it is clear that the product of the present invention provides tablets with sufficient compressive strength even at low compression pressures.

[Brief explanation of the drawing]

Figure 1 is an x-ray diffraction diagram of the compound of Example 4, Figure 2 is a differential thermal analysis curve of the compound of Example 4, and Figure 3 is a differential thermal analysis curve of the compound of Example 4.
The figure shows an infrared absorption spectrum of the compound of Example 4,
Figure 4 is the Fuchs curve of the compound of Example 4, and Figure 5 is the Fuchs curve of the compound of Example 4.
The figure is an infrared absorption spectrum of the organic anion component extract of the compound of Example 6 and indomethacin, FIG. 6 is an X-ray diffraction diagram of the compound of Example 7, and FIG. This is the infrared absorption spectrum of the compound of
The figure is a differential thermal analysis curve of the compound of Example 7. O diagram O Z diagram - 319 O 4-l2 O 5 diagram O t box O diagram 7 diagram O 8 diagram

Claims (1)

[Claims] 1 The following general formula MgxAly(OH)_2_x_+_3_y_-_z(
A)_z・aROH In the formula, A is (i) (a) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the formula, R_1 is a hydroxyl group, acyloxy group, 3-trifluoromethyl phenylamino group, or 2,3 - Anion of a compound that is a dimethylphenylamino group, (b) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the formula, R_2 is a hydrogen atom or an anion of a compound that is a methyl group, (c) P-( anion of di-n-propylsulfanyl)-benzoic acid, (d) anion of 1-(P-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid, (v) 2-phenyl-4 - an anion of carboxy-quinoline, or (f) an anion of sulpirine, or (ii) an anion of (a) to (f) above and a halogen ion, nitrate ion, carbonate ion, or sulfuric acid ion in an amount of 50 mol% or less based on the total anions. ion, R is a hydrogen atom or an ethyl group, x, y, z and a are
is a positive number satisfying the formula 1/4≦x/y≦8 1/(20)<x/(x+y)≦1 0.25a/(x+y)≦1, and has a composition represented by Substantially the following X-ray diffraction image, dÅ Relative intensity 15.23-44.14 6 7.96-21.02 100 3.93-9.40 40 2.61-6.41 20 2.34 21 2 .00 22 1.76 4 1.66 4 1.53 9 1.50 11 A method for producing a compound having the same X-ray diffraction pattern as (a) formula MgX_2 where X is a monovalent inorganic anion (b) a compound of the formula AlY_3 in which Y is a monovalent inorganic anion or a lower alkoxy group or an alkali metal aluminate; and (c)
Formula AM In the formula, M is a hydrogen atom or an alkali metal, and A has the above-mentioned meaning because the raw material mainly consisting of the compound is reacted under conditions of pH 8.0 or higher and in water or lower alcohol. A method for producing the compound comprising: 2 General formula MgxAly(OH)_2_x_+_3_y_-_z(
A)_z・aROH In the formula, A is (i) (a) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the formula, R_1 is a hydroxyl group, acyloxy group, 3-trifluoromethyl phenylamino group, or 2,3 - Anion of a compound that is a dimethylphenylamino group, (b) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the formula, R_2 is a hydrogen atom or an anion of a compound that is a methyl group, (c) P-( anion of di-n-propylsulfanyl)-benzoic acid, (d) anion of 1-(P-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid, (v) 2-phenyl-4 - an anion of carboxy-quinoline, or (f) an anion of sulpirine, or (ii) an anion of (a) to (f) above and a halogen ion, nitrate ion, carbonate ion, or sulfuric acid ion in an amount of 50 mol% or less based on the total anions. ion, R is a hydrogen atom or an ethyl group, x, y, z and a are
is a positive number satisfying the formula 1/4≦x/y≦8 1/(20)<z/(x+y)≦1 0.25z/(x+y)≦1, and has a composition represented by Substantially the following X-ray diffraction image, dÅ Relative intensity 15.23-44.14 6 7.96-21.02 100 3.93-9.40 40 2.61-6.41 20 2.34 21 2 .00 22 1.76 4 1.66 4 1.53 9 1.50 11 A method for producing a compound having the same X-ray diffraction pattern as (a) formula MgX_2 where X is a monovalent inorganic anion (b) a compound of the formula AlY_3 in which Y is a monovalent inorganic anion or a lower alkoxy group or an alkali metal aluminate; and (c)
Formula AM In the formula, M is a hydrogen atom or an alkali metal, and A has the above-mentioned meaning. A raw material mainly consisting of a compound is reacted in water or a lower alcohol under conditions of pH 8.0 or higher, and then A process for producing said compound, which comprises contacting the resulting precipitate with an aqueous solution of a compound of the formula AM, in which A and M have the meanings given above.