JPH0648950A - Antiulcer agent - Google Patents

Abstract

PURPOSE:To obtain an antiulcer agent, especially a medicine for treating and preventing ulcer caused in digestive organs such as gastric ulcer or duodenal ulcer. CONSTITUTION:The antiulcer agent is characterized by including at least one of zinc salt of an acidic polysaccharide selected from agaropectin, carrageenan, alginic acid, etc., of agar derived from seaweeds, hyaluronic acid which is a mucopolysaccharide, a compound prepared by applying an acidic group to a neutral polysaccharide and pectic acid, etc., contained in plants as an active ingredient.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anti-ulcer agent, and more particularly to an effective therapeutic and prophylactic drug for ulcers occurring in the digestive organs such as gastric ulcer and duodenal ulcer.

[0002]

2. Description of the Related Art In recent years, digestive system diseases as well as cardiovascular system diseases are extremely common diseases. Among them, peptic ulcer occurring in the stomach and duodenum is an adult disease with a high morbidity, and is said to be caused by alcohol drinking, stress and the like. Such an ulcer is not only accompanied by pain, but also becomes difficult to be completely cured due to becoming chronic, and sometimes serious problems such as bleeding, peritonitis, and canceration are caused. So, as a remedy for peptic ulcer,
Many drugs have been studied, and among them, drugs derived from sugar have been reported. For example, "oral therapeutic agent for digestive tract ulcer" for carrageenan (JP-A-57-38722), Murakami et al., Anti-ulcer property of agaropectin partial hydrolyzate (CA 77 .; 52).
304), and Asahi Misaki and others report on the anti-pepsin action of carrageenan (Takeda Research Institute Annual Report No. 24, 1965).
However, its efficacy was insufficient to be used as a therapeutic drug. Sucralfate, which is an aluminum salt prepared by introducing a sulfate group into sucrose, is a widely used antiulcer drug.

[0003]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide an anti-peptic ulcer therapeutic agent which is highly effective by using acidic polysaccharide as a raw material.

[0004]

[MEANS FOR SOLVING THE PROBLEMS] The present invention is noted for its action on the immune system and acidic polysaccharides which have an antiulcer effect but cannot be said to have a sufficient effect as a therapeutic drug. It was made based on the finding that an excellent anti-ulcer drug can be obtained by binding zinc that is present. That is, the present invention provides an anti-ulcer agent characterized by containing at least one zinc salt of an acidic polysaccharide as an active ingredient. The acidic polysaccharide as a raw material of the anti-ulcer agent of the present invention is agar pectin, carrageenan, alginic acid of agar derived from seaweed,
Funolan and the like, mucopolysaccharides such as hyaluronic acid, heparin and chondroitin sulphate, dextran sulphate, laminaran sulphate, carboxymethyl cellulose, compounds in which an acidic group is added to a neutral polysaccharide such as carboxymethyl starch, and pectin contained in plants. Examples include acids. However, as a raw material of the drug of the present invention, it is inexpensive and easily available to use an acidic polysaccharide derived from seaweed, and,
High content of acidic groups is desirable. Examples of the seaweed as a raw material include the red-weed plant's weedy eyes, sea urchin eyes, weeping eyes, crebu and nemia eyes, sugiuri eyes, dull eyes, and iris eyes. , Shiomidoro eyes, whip eyes,
Single or multiple polysaccharides containing a sulfate group, pyruvate group, or carboxyl group extracted from seaweeds of Amamigusa, Nagamatsumochi, Urushigusa, Hadamodoki, Konbume, and Hibameme are used. It is possible. It is preferable to use protozoa having a high content of polysaccharides containing a large amount of acidic groups such as alginic acid and λ-carrageenan. Extraction of these polysaccharides may be performed with cold water or warm water, or may be performed after an alkali treatment or an acid treatment that is performed when producing agar or carrageenan. Further, a method of performing extraction after treatment with a hydrolase such as cellulase can also be selected. It is preferable to avoid excessive alkali treatment in order to leave many acidic groups. The acidic polysaccharides extracted from seaweed are
It is possible not only to use it as a raw material as it is, but also to add an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid or the like, and an organic acid such as citric acid, malic acid, tartaric acid, etc. to hydrolyze it to lower its molecular weight and use it. . It is also possible to lower the molecular weight of the extracted acidic polysaccharide with a hydrolase such as agarase, cellulase, or alginate lyase, but the means for lowering the molecular weight is not limited to these.

The acidic polysaccharide used in the present invention has a molecular weight of several thousand or more, preferably tens of thousands or more. Moreover, examples of the acidic group contained in the acidic polysaccharide include a sulfuric acid group, a carboxyl group, a pyruvic acid, and a sulfite group. The content of the acidic group contained in the acidic polysaccharide is preferably 2 to 25% by weight, and more preferably 5% by weight or more, if the polysaccharide has a sulfate group. It is also preferable that at least one acidic group such as uronic acid and pyruvic acid is contained in 9 molecules of the constituent sugar, and preferably at least one is contained in 4 molecules of the constituent sugar. In the acidic polysaccharide and its low molecular weight product, or a mixture thereof, at least a part of the acidic groups contained in the acidic polysaccharide forms a salt with zinc. For example, to allow acidic polysaccharides to coexist with water-soluble inorganic zinc compounds such as zinc sulfate, zinc chloride, zinc bromide, zinc fluoride and zinc iodide and zinc salts of organic acids such as zinc acetate, zinc carbonate and zinc lactate. Thus, the zinc salt of these acidic polysaccharides can be easily obtained. More preferably, a cation exchange resin such as Amberlite I
It may be allowed to pass through R-120B, Diaion SK-1B, or the like to remove the cations that bind to the acidic groups of the acidic polysaccharide, and then coexist with the zinc compound. Furthermore, under acidic condition with metallic zinc,
It can also be obtained by coexisting with these acidic polysaccharides. However, the method for preparing the zinc salt of the acidic polysaccharide is not limited to these.

The zinc salt of the acidic polysaccharide according to the present invention has a zinc content of 30% by weight or less, preferably 5 to 20% by weight. In other words, when all the cations that bind to the acidic groups of the polysaccharide are replaced with zinc, the maximum content is reached and the amount of zinc added to the acidic polysaccharide is reduced, and the amount of zinc that is not a zinc salt is also increased, or other sugars and proteins The zinc content can be adjusted by adding. Excessive zinc ions that are not bound to the acidic groups of the acidic polysaccharide are subjected to ultrafiltration with a cut-off molecular weight of about 10,000 daltons, and hydrophilic organic solvents such as acetone, ethyl alcohol and methyl alcohol are added at 30 to 80% V / V can be added to precipitate and separate the acidic polysaccharide and its zinc-bound product. Further, by combining or repeating these methods, it is possible to remove free salts, zinc ions, and low molecular weight organic substances for purification. When these treatments are performed, there is no particular limitation except that the treatment is performed at a pH at which zinc does not become insoluble as hydroxide. The zinc salt derived from the acidic polysaccharide according to the present invention has a stomach or duodenal ulcer by itself or by mixing with an inert carrier and / or a diluent or the like, as a powder, a tablet, or by mixing with other foods or the like. It is advisable to orally administer 20 to 500 mg of zinc per day to the patient. Further, the zinc salt can be administered as a powder, tablets, or mixed with foods even if it is not dissolved in water.

[0007]

INDUSTRIAL APPLICABILITY According to the present invention, zinc salts of acidic polysaccharides have significantly higher anti-ulcer properties than the use of each acidic polysaccharide or zinc agent alone, and the protective effect of protecting the digestive mucosa. Not only can it be used as a therapeutic or prophylactic agent that also has an aggressive effect of suppressing the secretion of digestive juices. Next, the present invention will be described with reference to examples.

[0008]

【Example】

Example 1 λ-carrageenan (product code: M) of Taito Seaweed Co., Ltd.
To 80 g of (L-300), 800 ml of 0.04N HCl was added, and the mixture was heated to 70 ° C. while stirring well. Hydrolysis was continued while measuring the viscosity with a B-type viscometer, and 100 g of each was extracted three times over time and neutralized with an aqueous NaOH solution. To each of the collected λ-carrageenan, 1 liter of pure water and 5 g of zinc chloride were added, and a test ultrafiltration device (pump LP-3000, membrane module UF-L) manufactured by Tosoh Corporation was added.
Two pieces (total 400 cm ² ) of ultrafiltration membrane UF-2CS-10PS (molecular weight cutoff of 10,000 dalton) were attached to MS II) and ultrafiltration was continued while supplementing pure water. Even if the filtrate was made alkaline, if it did not become cloudy, it was concentrated and freeze-dried. The yields of these samples were 7.9 g, 7.8 g and 6.6 g, respectively. The zinc salt prepared from 100 g of the sol before hydrolysis had a yield of 8.2 g. The analytical values of the zinc salt of λ-carrageenan thus prepared are shown in Table 1.

[0009]

[Table 1] Table 1 Analysis value of each sample using λ-carrageenan as a raw material Sample MW ^* Ash content ^** Na K Ca Mg Fe Zn Remark ppm ppm ppm ppm ppm ppm λ-1> 85 × 10 ⁴ 18.8% 4020 2370 157 1660 107 107000 Unhydrolyzed λ-2 10.3 × 10 ⁴ 21.9% 6610 2780 180 1670 133 119000 λ-3 7.4 × 10 ⁴ 21.8% 5320 2580 120 1490 278 106000 λ-4 1.4 × 10 ⁴ 20.0% 6080 3330 190 1900 135 91900 * Calculated from calibration curve of pullulan molecular weight standard *** Sulfated ash In addition, the antiulcer effect of these samples was evaluated by gastric ulcer model system using rats.
Shown in the table. As an evaluation method, a predetermined dose of λ-carrageenan zinc salt in an aqueous solution was orally administered to a rat, and 1 hour later, 1.5 ml of 60% ethanol containing 150 mM HCl was orally administered. One hour after that, the rat was sacrificed, the length of the ulcer generated in the stomach was measured, and the total value of all ulcers was taken as the total ulcer value. In addition, commercially available cetraxate was used as a control drug. From the results shown in Tables 2 and 3, it is clear that the drug according to the present invention has an extremely high anti-ulcer effect based on the protective effect on the gastric mucosa. The effect of the marketed drug cetraxate was exceeded in all samples.

[0010]

[Table 2] Table 2 Evaluation of anti-ulcer property on rats treated with HCl-ethanol (I) Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-6 110.1 ± 10.8 **-λ-1 200 5 0.0 ± 0.0 ** 100.0 λ-2 200 6 3.2 ± 2.3 ** 97.1 λ-3 200 6 0.9 ± 0.5 ** 99.2 λ-4 200 6 0.0 ± 0.0 ** 100.0 Cetraxate 300 6 4.0 ± 2.6 ** 96.4 ** p <0.01 Control only purified water

[0011]

[Table 3] Table 3 Evaluation of anti-ulcer property on rats treated with HCl-ethanol (II) Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-7 108.0 ± 8.5 − λ-1 100 6 1.7 ± 1.1 ** 98.4 50 6 15.3 ± 4.8 ** 85.8 λ-2 100 5 0.4 ± 0.2 ** 99.6 50 5 15.2 ± 6.0 ** 85.9 λ-3 100 5 0.3 ± 0.3 ** 99.7 50 5 12.6 ± 3.6 ** 88.3 λ-4 100 6 1.8 ± 1.4 ** 98.3 50 6 21.3 ± 7.0 ** 80.3 Cetraxate 300 5 16.7 ± 6.6 ** 84.5 ** p <0.01 Control only purified water .

Example 2 Using the same zinc salt of acidic polysaccharide as the sample used in Example 1, the inhibitory effect on the secretion of digestive juice, that is, the inhibitory effect on the attack factor of the drug according to the present invention was investigated. The test method was as follows: the rat was laparotomized, the stomach contents were removed, the pylorus was ligated, and the aqueous solution of the sample was administered inside the duodenum. Four hours after the pylorus ligature was sacrificed, the gastric juice volume, gastric juice pH, and gastric juice acidity were measured. The marketed drug cimetidine was used as a control. The test results are shown in Table 4, but it is clear that the secretion of gastric juice and the acidity of gastric juice are suppressed.

[Table 4] Table 4 Effect on gastric juice Sample dose N Volume pH Acidity Acid output (mg / kg) (ml) (m Eq / 1) (μEq / 4hr.) Control ─ ─ 5 5.1 ± 1.1 1.4 ± 0.0 86.0 ± 8.2 467.6 ± 139.0 λ-1 100 5 1.8 ± 0.2 * 1.7 ± 0.1 * 82.0 ± 8.6 147.3 ± 31.4 50 5 3.1 ± 0.7 1.4 ± 0.0 100.4 ± 4.4 319.4 ± 84.8 λ-2 100 4 2.2 ± 0.4 2.0 ± 0.1 * * 116.5 ± 13.0 252.6 ± 66.2 50 4 4.7 ± 1.3 1.8 ± 0.1 ** 105.0 ± 10.0 507.8 ± 161.7 λ-3 100 5 2.0 ± 0.5 * 2.1 ± 0.1 ** 95.2 ± 15.4 207.5 ± 77.2 50 5 3.6 ± 0.5 1.8 ± 0.1 * 114.4 ± 3.7 * 406.6 ± 50.7 λ-4 100 5 3.2 ± 0.8 2.0 ± 0.1 ** 115.2 ± 7.4 * 373.8 ± 106.7 50 5 4.8 ± 1.6 1.8 ± 0.1 ** 109.6 ± 10.0 593.3 ± 225.0 Cimetidine 150 5 2.1 ± 0.5 * 2.4 ± 0.0 ** 46.8 ± 5.3 ** 106.7 ± 32.6 * p <0.05 * * p <0.01 Control only purified water

Example 3 The antiulcer properties of zinc salts of alginic acid, agar, ι-carrageenan and κ-carrageenan were examined. Alginic acid was added to Kibun Food Chemifa Co., Ltd.
Suspended in 00 ml water, added 5 g zinc chloride, then NaOH
The solution was adjusted to about pH 5 with an aqueous solution, filtered, and the filter cake was thoroughly washed with pure water and dried to obtain about 4.6 g of zinc alginate.
For agar, 100 g of dried Chilean gonorrhoeae algae was soaked overnight, then boiled and extracted with 4 liters of water, and the agar solution obtained by filtering diatomaceous earth was recovered by precipitation by adding acetone, and dried to about 8 g. Got the agar. 5.8g of this agar is added to hot water 100
Swell with ml and add HCl to pH 2 at 65 ° C, 40
Hydrolyzed for a minute. Add 2.5 g of zinc chloride to this and add NaOH
The pH was adjusted to 4.8 with an aqueous solution, and the ultrafiltration device used in Example 1 was used to perform filtration while adding pure water to desalt and purify. The yield was 4.2 g. ι-carrageenan, and κ
-Carrageenan (Tight-Seaweed Co., Ltd. product code: ML-
320, CHP) is 100 g of hot water for each 10 g.
Add 70 ml to swell and adjust to pH 1.8 with HCl, then 70 ℃, 2
It was hydrolyzed by stirring for a time. To each of this low molecular weight carrageenan, add 5 g of zinc chloride, and add pH 4.5 with NaOH aqueous solution.
And purified by adding ultrapure water using the ultrafiltration device used in Example 1 for desalting and purification. The analytical values of the prepared samples are shown in Table 5, and the results of the antiulcer test by the method shown in Example 1 are shown in Table 6. Except for agar, which had a low zinc content, high antiulcer activity was observed. In particular, alginic acid, like λ-carrageenan, has a very high antiulcer property in its zinc salt. That is, the higher the amount of zinc bound to the acidic groups of the acidic polysaccharide, the higher the antiulcer property was obtained. The zinc salt of alginic acid is 1 / th of the marketed drug cetraxate
The same effect was obtained with three doses.

[Table 5] Table 5 Analytical values of samples prepared from seaweed polysaccharides Sample M. W. * Na ppm K ppm Zn ppm Alginic acid 3.1 × 10 ⁴ 4000 85 144000 Agar 14.0 × 10 ⁴ 463 66 27000 κ-Carrageenan 6.4 × 10 ⁴ 4230 6340 55100 ι-Carrageenan 14.0 × 10 ⁴ 2740 2620 72500 * Calculated from the calibration curve of pullulan molecular weight standard

[0014]

[Table 6] Table 6 Evaluation of anti-ulcer property on rats treated with HCl-ethanol (III) Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-6 69.6 ± 7.7-Alginic acid 100 6 2.3 ± 2.0 ** 96.7 200 6 0.2 ± 0.2 ** 99.7 Agar 200 6 41.4 ± 14.9 40.5 κ-carrageenan 100 6 15.3 ± 8.6 ** 78.0 200 6 11.8 ± 5.9 ** 83.0 ι-carrageenan 100 5 27.4 ± 8.2 ** 60.6 200 5 1.0 ± 0.5 ** 98.6 Cetraxate 300 6 1.8 ± 0.8 ** 97.4 ** p <0.01 The control is pure water only.

Example 4 3 g of 5 g of dextran sulfate sodium (for biochemistry, 500,000 daltons) and 5 g of zinc chloride manufactured by Wako Pure Chemical Industries, Ltd.
It was dissolved in 00 ml of pure water and centrifuged at 10,000 rpm for 10 minutes to remove insoluble matter. Then add about 150 ml
After concentration under reduced pressure, 350 ml of ethanol was added to precipitate the polysaccharide, which was filtered, washed with 50% ethanol and dried to obtain 4.43 g of a dextran sulfate zinc salt. The zinc content of this sample was 4.58% by weight, and the molecular weight measured with pullulan as the standard molecular weight was 17.0 × 10 ⁴ dalton. According to Example 1, the anti-ulcer effect was evaluated by a model system of gastric ulcer by HCl-ethanol using rats. The evaluation results are shown in Table 7, but the effect is clear.

[Table 7] Table 7 Anti-ulcer evaluation of dextran sulfate zinc salt on HCl-ethanol-treated rats (IV) Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-6 73.1 ± 16.3-Dextran sulfate 100 6 21.3 ± 5.0 * 70.9 Cetraxate 300 6 9.3 ± 3.9 * 87.2 * p <0.05

Example 5 2 g of sodium chondroitin sulfate C and 5 g of zinc chloride from Nacalai Textile Co., Ltd. were dissolved in 100 ml of pure water to prepare 1
Insoluble matter was removed by centrifugation at 5,000 rpm for 15 minutes. Next, Tosoh Corporation's test ultrafiltration device (pump L
P-3000, Membrane Module UF-LMS) was equipped with an ultrafiltration membrane UF-10PS (molecular weight cutoff of 10,000 dalton), and ultrafiltration was continued while supplementing pure water. When the filtrate did not become cloudy even after being made alkaline, it was concentrated under reduced pressure and lyophilized. The yield was 1.84g. The zinc salt has a sodium content of 2700 ppm and a zinc salt content of 11.2.
The weight percentage and the sulfate group content were 17.8 wt%. According to Example 1, the anti-ulcer effect was evaluated by a model system of gastric ulcer by HCl-ethanol using rats. The evaluation results are shown in Table 8, and the extremely high effect was obtained even by the administration of 50 mg / kg.

[Table 8] Table 8 Antiulcer evaluation of zinc chondroitin sulfate on rats treated with HCl-ethanol (V) Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-5 86.2 ± 15.6- Chondrontin 50 6 5.8 ± 1.4 ** 93.3 Zinc sulfate 100 6 2.6 ± 1.7 ** 97.0 200 6 0.7 ± .4 ** 99.2 Cetraxate 300 6 13.4 ± 4.9 ** 84.5 ** p <0 .01

Comparative Example 1 The effects of various polysaccharides on ulcer caused by administration of HCl-ethanol were examined. As the polysaccharides, all commercially available food products were used, and the evaluation method was carried out by the method shown in Example 1. The evaluation results are shown in Table 9, but there is no effective anti-ulcer property other than carrageenan, and especially the inorganic salt zinc chloride has no ulcer-suppressing effect. However, this carrageenan is also less effective than the effect of the zinc salt shown in Table 3 of Example 1.

[Table 9] Table 9 Anti-ulcer effect of polysaccharides and zinc chloride on rats treated with HCl-ethanol Sample dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-6 98.8 ± 15.7-Xanthan gum 100 6 118.8 ± 14.1 -20.2 Guar gum 100 6 82.2 ± 11.8 16.8 Pectin 100 6 92.1 ± 15.8 6.8 Curdlan 100 6 111.6 ± 21.7 -13.0 Agar 100 6 78.1 ± 17.9 21.0 Agar 250 5 86.0 ± 11.0 13.0 Carrageenan 250 5 12.5 ± 3.8 ** 87.3 Cetraxate 300 5 5.1 ± 1.2 ** 95.7 Zinc chloride 300 6 113.5 ± 18.2 -14.9 ** p <0.01 The control is pure water only.

Comparative Example 2 From Comparative Example 1, carrageenan itself has antiulcer properties, but commercially available carrageenan forms salts with various metal ions such as sodium, potassium and calcium. Therefore, in order to confirm the effectiveness of the zinc salt, magnesium salt and aluminum salt were prepared and the effect on HCl-ethanol ulcer was investigated using rats.
The sample is Carrageenan ML-30 from Taito Seaweed Co., Ltd.
After acid hydrolysis using 0 as a raw material, a magnesium salt was obtained. In other words, carrageenan ML-300 100 g 0.0
Add 1 liter of 4N HCl water and stir about 65
The sample was heated to 0 ° C. and 3 samples of 100 g were collected over time. To this, 10 g of magnesium sulfate heptahydrate was added, adjusted to pH 4.5 with an aqueous solution of NaOH, stirred well, and then poured into 500 ml of acetone. The formed precipitates were collected by filtration, washed with 100 ml of acetone, then added with about 100 ml of pure water and concentrated under reduced pressure.
Acetone was removed. Further, this solution was added to 1 liter of pure water, filtered with water using the ultrafiltration device used in Example 1 while being sufficiently desalted, and then freeze-dried to obtain about 8 g each. Aluminum salt is the lowest molecular weight sol 1 of this acid hydrolyzate of carrageenan ML-300.
To 00 g, 10 g of aluminum sulfate hexahydrate was added to adjust the pH to 4.5, and then the same treatment as the magnesium salt was carried out to prepare. The yield was about 7 g. The analytical values of the obtained samples are shown in Table 8 and the test results of the antiulcer effect are shown in Table 10. From the results of this test, magnesium salt rather promotes ulcer, and aluminum salt also has insufficient antiulcer effect as a therapeutic agent. In short, the acid ulcer derived from seaweed exerts the maximum antiulcer effect by using zinc salt.

[Table 10] Table 10 Analysis table for Mg and Al salts of λ-carrageenan Sample MW ^* Ash content ^** Na K Ca Mg Fe Remark ppm ppm ppm ppm ppm 1> 85 × 10 ⁴ 19.3% 5270 2980 794 89000 77 Mg Salt 2 24 × 10 ⁴ 17.5% 9580 6960 2520 28800 167 〃 3 12 × 10 ⁴ 19.8% 3150 1820 822 30500 80 〃 4 3.2 × 10 ⁴ 19.8% 3480 1610 756 28700 143 〃 λ-Al 2.7 × 10 ⁴ 18.7% 5320 3500 1020 25400 95 Al salt ML-300 ＞ 85 × 10 ⁴ 26.6% 74700 24400 1630 5350 249 Raw material * Calculated from the calibration curve of pullulan molecular weight standard ** Sulfate ash

[0019]

[Table 11] Table 11 Antiulcer Evaluation of Mg and Al Salts on HCl-Ethanol-administered Rats Sample Dose N Total ulcer value (mm) Suppression rate (mg / kg) (Mean ± SE) (%) Control-5 75.2 ± 13.0 -1 200 5 90.0 ± 15.0 -19.7 2 200 5 88.1 ± 13.4 -17.2 3 200 5 89.8 ± 16.9 -19.4 4 200 5 78.3 ± 17.5-4.1 λ-Al 100 6 51.7 ± 5.6 * 31.3 200 6 56.7 ± 14.2 24.6 Cetraxate 300 4 1.1 ± 0.7 ** 98.5 * p <0.1 ** p <0.01 The control was administered with purified water only. The present inventors are keen to develop a superior anti-digestive ulcer drug. As a result of repeated research, an extremely high anti-ulcer drug was invented by a simple production method using a natural acidic polysaccharide as a raw material.

Claims (2)

[Claims] 1. An anti-ulcer agent comprising at least one zinc salt of an acidic polysaccharide as an active ingredient. 2. An anti-ulcer agent comprising at least one zinc salt of a low molecular weight compound of acidic polysaccharide as an active ingredient.