JPH07238019A - Water-soluble taurine zinc compound - Google Patents

Abstract

PURPOSE:To obtain an antihepatitis agent, hepatic function improving agent and antiulcer agent having excellent antihepatitis action, hepatic function improving action and antiulcer action and low toxicity by using a water-soluble taurine zinc compound as an active component. CONSTITUTION:This antihepatitis agent, hepatic function improving agent and antiulcer agent contains a water-soluble taurine zinc compound of formula I (A is an organic acid) (e.g. taurine zinc malonate) as an active component. The compound of formula I can be produced by reacting the compound of formula II with an organic acid such as acetic acid, glycolic acid and lactic acid. Since the compound of formula I is soluble in water and has excellent stability, it can be used in wide field in the form of injection and liquid as well as tablet, granule, etc.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an anti-hepatitis agent, a liver function improving agent and an anti-ulcer agent containing a water-soluble taurine zinc compound as an active ingredient.

[0002]

[Prior Art] Expression

[Chemical 2] It has already been reported by the present inventors that taurine zinc represented by the following formulas has superior anti-hepatitis action, liver function improving action and anti-ulcer action as compared to taurine, glutathione and glycyrrhizin (Japanese Patent Application No. -186090). However, since this zinc taurine is insoluble in water, it is impossible to produce a water-soluble preparation such as an injection.

[0003]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention The present inventors have conducted various studies on water-solubilization of taurine-zinc in order to further increase the efficacy of taurine-zinc and to develop water-soluble preparations such as injections and solutions. It was found that this organic acid salt is soluble in water and excellent in stability, and further studies were conducted to complete the present invention.

[0004]

The present invention has the general formula (I)

[Chemical 3] (In the formula, A represents an organic acid) The present invention relates to an anti-hepatitis agent, a liver function improving agent, and an anti-ulcer agent containing a water-soluble taurine zinc compound represented by the formula.

The compound of the general formula (I) has the formula (II)

[Chemical 4] It is produced by reacting the compound of (1) with an organic acid. Examples of organic acids include acetic acid, glycolic acid, lactic acid, malonic acid, succinic acid, glutaric acid, malic acid, tartaric acid, maleic acid, fumaric acid and other aliphatic carboxylic acids, benzoic acid, salicylic acid, acetylsalicylic acid, phthalic acid and the like. Amino acids such as aromatic carboxylic acids, aspartic acid, glutamic acid, N-acetylglutamic acid, N-acetylcysteine and the like and derivatives thereof can be mentioned. The reaction is preferably carried out in an anhydrous solvent. Usually, the compound of formula (II) is added to an organic acid dissolved in a suitable solvent such as methanol or ethanol, and the mixture is stirred at room temperature or under heating for several minutes to several hours. To do.

The compound of the present invention has excellent anti-hepatitis action, liver function improving action and anti-ulcer action and has low toxicity. The compound of the present invention may be mixed with an appropriate excipient, carrier, or diluent which is itself or pharmacologically acceptable, to give tablets, capsules,
It can be used orally or parenterally in various forms such as granules, powders, troches, suppositories, and ointments. Further, since it is soluble in water, it can be used in a wide variety of applications such as injections, infusions, syrups, eye drops, coatings, nasal drops, gargles, and inhalation agents. The dose varies depending on the patient's symptoms, age, body weight, administration route, etc., but is usually 100 to 1000 mg per adult for oral administration.
~ 4 divided doses can be administered.

Hereinafter, the present invention will be described in more detail with reference to Examples and Examples of the present invention.

Reference Example An example of the synthesis of the compound of formula (II) is shown below.

100 ml of dry methanol was added to and dissolved in 11.3 g (0.05 mol) of zinc bromide, and 12.5 g (0.1 mol) of taurine and 19.3 ml of a 28% sodium methylate methanol solution (0. A solution prepared by dissolving 1 mol) in 220 ml of dry methanol was added dropwise with stirring at 60 to 70 ° C., and the mixture was stirred at the same temperature for 2 hours. After cooling, the deposited precipitate was collected by filtration and washed with dry methanol to obtain 22.6 g of colorless powder of taurine zinc. Melting point 330 ° C (decomposition)

[0010]

【Example】

Example 1 2.0 g (20 mmol) of malonic acid was added to anhydrous methanol 8
Dissolve in 0 ml and add taurine zinc 6.27 g to this solution.
(20 mmol) was added and the mixture was stirred at room temperature for 4 hours, and then methanol was distilled off under reduced pressure to obtain 8.06 g of a colorless powder of taurine zinc malonate. Melting point 250 ° C or higher. 1 g of this compound
Dissolves in 4.0 ml of water.

Elemental analysis value (%): C ₇ H ₁₆ N ₂ O ₁₀ S ₂ Zn calculated value C: 20.32, H: 2.92, N: 6.7
7, Zn = 15.80 Found C: 20.08, H: 3.21, N: 6.6
3, Zn = 15.41 IR (KBr, cm ⁻¹ ): 3210, 3048, 2
970, 1617, 1576, 1508, 1458, 1
388, 1305, 1213, 1180, 1114, 1
102,1038

Example 2 3.60 g (20 mmol) of acetylsalicylic acid was dissolved in 60 ml of anhydrous methanol, 3.14 g (10 mmol) of zinc taurine was added to this solution, and the mixture was stirred at room temperature for 7 hours, and then methanol was distilled off under reduced pressure. As a result, 6.52 g of colorless powder of taurine zinc diacetylsalicylate was obtained. Melting point 12
5 ° C (decomposition). 1 g of this compound is dissolved in 12.0 ml of water.

Elemental analysis value (%): C ₂₂ H ₂₈ N ₂ O ₁₄ S ₂ Zn calculated value C: 39.21, H: 4.19, N: 4.1
6, Zn: 9.70 actual value C: 38.95, H: 4.40, N: 4.2
0, Zn: 9.45 IR (KBr, cm ⁻¹ ): 3219, 3149, 30
84, 3047, 2968, 1749, 1616, 15
12, 1486, 1458, 1397, 1345, 13
05,1218,1111,1037

Example 3 1.89 g (10 mmol) of N-acetyl-L-glutamic acid was dissolved in 100 ml of anhydrous methanol, 3.14 g (10 mmol) of zinc taurine was added to this solution, and the mixture was stirred at room temperature for 5 hours and then methanol. Was distilled off under reduced pressure to obtain 4.97 g of colorless powder of taurine zinc N-acetyl-L-glutamic acid salt. Melting point 224 [deg.] C (decomposition). This compound 1
g is dissolved in 5.6 ml of water.

Elemental analysis value (%): C ₁₁ H ₂₃ N ₃ O ₁₁ S ₂ Zn calculated value C: 26.28, H: 4.61, N: 8.3
6, Zn: 13.00 Found C: 25.98, H: 4.97, N: 8.0
9, Zn: 13.11 IR (KBr, cm ^-1 ): 3298, 3215, 30
53, 2970, 1718, 1618, 1512, 14
58, 1409, 1344, 1305, 1223, 11
81, 1112, 1039

Examples 4 to 8 According to Examples 1 to 3, water-soluble taurine zinc compounds included in the general formula were obtained. The appearance, melting point, elemental analysis value, and solubility of the product are shown in Table 1.

[0017]

[Table 1]

Example 9 Tablets The following ingredients were used to prepare the twelfth revised Japanese Pharmacopoeia formulation general rule 15:
Tablets were produced according to the section. Adults can take 2 to 3 tablets 3 times a day.

Example 10 Lozenge Agent The following ingredients are used to prepare the twelfth revised Japanese Pharmacopoeia General Regulations 21
A lozenge was prepared in accordance with the section. Take one adult once in the mouth several times a day and slowly dissolve without chewing.

Example 11 Ointment Taking the following ingredients, the 12th revised Japanese Pharmacopoeia Preparation General Rule 22
An ointment was produced according to the section. Use it by rubbing or applying an appropriate amount on the affected area several times a day.

Example 12 Suppository Taking the following ingredients, the 12th revised Japanese Pharmacopoeia General rule 12
The suppository was manufactured according to the section. It is administered once in the anus once or twice a day.

Example 13 Inhalant An inhalant was prepared according to a conventional method by using the following ingredients. Use by inhaling 50 to 100 ml once several times a day.

Example 14 Coating Agent A coating agent was prepared according to a conventional method by using the following components. Use by applying an appropriate amount several times a day.

[0024]

EFFECTS OF THE INVENTION Taurine zinc has an obviously superior anti-hepatitis action, liver function improving action and anti-ulcer action as compared to taurine, glutathione and glycyrrhizin, but since it is insoluble in water, a water-soluble preparation can be produced. could not. On the other hand, since the compound of the present invention is soluble in water and excellent in stability, it can be used in a wide variety of applications such as tablets, granules, injections, liquids and the like.

Claims (1)

[Claims] 1. A general formula: An anti-hepatitis agent, a liver function improving agent, and an anti-ulcer agent containing a water-soluble taurine zinc compound represented by the formula (wherein A represents an organic acid) as an active ingredient.