KR20050088816A - Antacid agent containing polysaccharide, crab and lobster shells, cuttlefish, chitin, chitosan and/or salt of chitosan - Google Patents

Abstract

The present invention is prepared using chitin or chitosan extracted from the shell of crab or shrimp, squid bone, or chitin or chitosan obtained by enzymatically decomposing the chitin or chitosan, or an oligosaccharide, and adsorbing hydrochloric acid secreted from the stomach. It is to provide an antacid in the form of liquid, powder, capsule or tablet which is excellent in effect and not temporary neutralization, and can enhance the regeneration, gastric wall protection and immunity of cells as well as treatment of gastrointestinal inflammation.

Description

Antacid agent containing polysaccharide, crab and lobster shells, cuttlefish, chitin, chitosan and / or salt of chitosan}

The present invention relates to an antacid made of polysaccharide, crab or shell of shrimp, squid bone, chitin, chitosan, chitosan. More specifically, the present invention is prepared by using chitin or chitosan extracted from shells of crab or shrimp, squid bones, or chitin and / or chitosan obtained by enzymatically decomposing the chitin or chitosan, or oligosaccharides. The present invention relates to an antacid in the form of liquid, powder, capsule or tablet which is excellent in controlling the hydrochloric acid secreted in the stomach and is not temporary neutralization, which is capable of treating gastric wall inflammation and regenerating cells, protecting the gastric wall and enhancing immunity. .

Due to the complexity of modern society and changes in diet, many people suffer from gastritis and gastrointestinal diseases caused by stress and food. To get rid of these pains, I am taking antacids. Antacids are used for the treatment of gastritis, gastric acidosis, gastric ulcer and duodenal ulcer. Neutralizes hydrochloric acid in gastric juice to reduce stomach acid irritation of the stomach wall, relieves pain, and inactivates pepsin to prevent the development of ulcers. In addition, there is an effect of protecting the inflammatory site by the action of buffering, adsorption, coating degree. Efficacy should be rapid and sustained, and the pH of gastric juice should be maintained in the desired range to be the ideal antacid.

The efficacy is evaluated by the reaction rate, duration, antacid ability, peak pH, etc. after taking antacids. Although the evaluation criteria are not constant, it is ideal to maintain a pH range of 3.0 to 3.5 during oral administration. If the pH is too large to maintain a high pH of 7 or more, acid rebound may occur when the antacid is administered for a long time. In particular, the antacids used to treat gastritis or gastric ulcers are mostly alkaline metal salts, and aluminum hydroxide is used. In addition, the disadvantages of taking a long time may cause side effects such as metabolic alkylosis and acid rebound.

In addition, diseases such as gastritis and gastric ulcers are difficult to cure and the possibility of recurrence is high, so the treatment with only the antacid effect is bound to reach a limit. The role as an antacid is to put together a temporary antacid effect to fundamentally solve the causes of diseases such as gastritis and gastric ulcers.

Accordingly, the present inventors have made intensive studies to solve the conventional problems, and as a result, they have developed a new antacid with polysaccharides chitin and chitosan, and derivatives thereof. The present invention has been reached.

The present invention has a long time period for taking antacids made by chemical synthesis and is made of alkaline metal salts, and is mainly mixed with a large amount of aluminum hydroxide (Al _X (OH) _Y ), and simply has a function of neutralizing hydrochloric acid as gastric acid. It's hard to expect It is also strongly alkaline, causing side effects such as metabolic alkylosis. It aims to manufacture eco-friendly chitin or chitosan antacids, which are not biocompatible and chemically synthetic, that can solve these problems and coat gastric walls or barriers and treat the underlying causes of gastritis and gastric ulcers that can be expected to regenerate inflammatory cells. This is similar to the old days when we used squid bones for wound healing.

The biocompatible antacid of the present invention for achieving the above object is a chitin or chitosan known as a functional new material of food, or chitosan salt, or chitin or chitosan obtained from chitin, or a chemical treatment or enzymatic method, ie Aeromonas genus or Bacillus genus (bacillus genus) SP.) The degree of polymerization degraded using enzymes obtained using microorganisms of origin, chitin and chitosan monosaccharides (glucosamine), chitin and chitosan oligosaccharides or sodium alginate, starch, mannose, water-soluble substances in all pH ranges from 1 to 15. It is characterized in that it is prepared in powder, tablet or liquid containing polysaccharides such as cellulose, hyaluronic acid, agarose, galactomannan, agar, carrageenan.

That is, the present invention prepared chitin and chitosan, water-soluble high molecular chitosan, chitosan salt, chitosan oligosaccharides and compared the antacid ability of the commercially available antacids with the materials prepared according to this method, the antacid ability similar to conventional antacids It was confirmed to have. Chitin and chitosan had the functions of treating inflammatory cells, antimicrobial activity, cholesterol excretion, and fat excretion, but the present invention has been developed by applying this function to develop a highly functional antacid that has high antagonism and biocompatibility and regenerates inflammatory cells. It is done.

On the other hand, chitin is composed of N-acetyl-D-glucosamine and D-glucosamine as shown by the following formulas (I) and (II), and constitutes a cell wall and shell skeleton of shellfish and insects. to be. The safety of chitin and chitosan, together with its water-soluble low molecular weight chitosan salts and oligosaccharides, has already been demonstrated, and it has anti-cancer effects, lowers blood cholesterol levels, suppresses hypertension, improves liver function, immune activity, intestinal function, and excretion of fat. It is already applied to food and pharmaceutical fields.

Chitin

Chitosan

Chitosan oligosaccharides and monosaccharides (glucosamine), which are water-soluble low-molecular substances, are those in which chitin or chitosan is decomposed to have a degree of polymerization of 1 to 15 N-acetyl-D-glucosamine or D-glucosamine by chemical or enzymatic treatment. It means water-soluble substance in neutral water.

In the accompanying drawings, Figure 1 illustrates a process for the separation and purification of chitin, the main raw materials of crab, shrimp, crayfish shells, desalting (immersion for 24 hours in 5% HCl solution), deproteinization (for 5 hours in 5% NaOH solution) Heating and washing) and depigmentation (washing and potassium permanganate or ultraviolet decomposition) to separate and purify chitin and chitosan to prepare chitin and chitosan. In addition, chitosan and oligosaccharides are separated into purified chitin and chitosan by chemical treatment or enzymes, as shown in FIG. 2, to prepare a solvated monosaccharide (glucosamine) and chitosan oligosaccharides.

In the above, the water-soluble monosaccharide (glucosamine) and oligosaccharide prepared by chemical treatment contain a large amount of salt and use it as it is. It may also be used to remove the insoluble matter after neutralization and purification. The preparation method of chitosan oligosaccharide is produced by adding, stirring and dissolving an inorganic acid or an organic acid to chitosan, and decomposing as shown in FIG. 2 using a purified degrading enzyme. The heat treatment is performed at the above temperature, and the insolubles are filtered out.

The acidic solution used in the decomposition may be selectively used one or two or more of hydrochloric acid, acetic acid, citric acid, lactic acid, ascorbic acid, malic acid, formic acid, propionic acid, adipic acid, oxycarboxylic acid.

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

Example 1

Crab, shrimp, and crayfish shells are ground and desalted by soaking in 5% HCl solution for 24 hours, followed by heating and washing for 5 hours in 5% NaOH solution for deproteinization, followed by washing and potassium permanganate or UV degradation. The chitin was separated and purified by decolorizing through. This chitin can be used as an antacid to treat stomach inflammation. The chitin is prepared according to the degree of deacetylation. An amino group exists in this chitosan, and gastric acid is adsorbed by this amino group. Thus, chitosan can be used as an antacid. The antacid test was carried out for this antacid, and the results are shown in Table 1 below.

The antacid test was performed as follows according to the antacid test method of the Korean Pharmacopoeia.

1) Raw materials and solid preparations

   According to the antacid test method of the Korean Pharmacopoeia, after measuring the mass of the product I company N, D company J product of the solid preparation and put into a 200ml flask was added 100ml 0.1M HCl. After closing, the mixture was shaken for 1 hour using a water tank shaker (37 ± 2 ° C.), followed by simple filtration using a filter paper. After the solution was cooled to room temperature, 50 ml of the filtrate was accurately taken, and the excess HCl was titrated with 0.1 M NaOH (end point pH 3.5). The blank test was carried out in the same manner.

2) Liquid formulation

The amount of the G product liquid company G was accurately taken into a 100 ml volumetric flask, and 100 ml was accurately filled with 50 ml of 0.2 M HCl and distilled water. After transferring to a 200ml flask, the residue was washed with 20ml of distilled water, and then the cap was closed and mixed by shaking for 1 hour using a water tank shaker (37 ± 2 ° C). Simple filtering using filter paper. After the solution was cooled to room temperature, 60 ml of the filtrate was accurately taken, and the excess HCl was titrated with 0.1 M NaOH (end point pH 3.5). The blank test was carried out in the same manner. In order to evaluate the antacid ability of commercially available antacids, the antagonist's antacid test method was applied to test the antacid ability. The dividing force can be determined by the following formula.

Antacid power (0.1M HCl consumption / Recovery capacity) (ml) = (b-a) × f × 2 × t ÷ s

a: 0.1 M NaOH solution consumption (ml), b: 0.1 M NaOH solution consumption (ml) in the blank test, f: 0.1M NaOH solution consumption coefficient, t: 1,000 mg raw material, a single dose of the formulation (high Brothers are mg, liquids are ml, s is the amount of sample (mg for raw and solid formulations and ml for liquid formulations). In the experiment, a fixed amount of commercial antacids (500mg) was determined to compare the antacid ability uniformly.

Example 2

The chitosan purified in Example 1 was dissolved by stirring with addition of an inorganic acid or an organic acid, and chitosan was decomposed at 37 to 50 ° C. for more than 24 hours using a purified chitosan degrading enzyme to obtain oligosaccharides, and chitosan, which is insoluble in neutral, was removed after filtration. It was. Herein, enzymes obtained using microorganisms of the genus Aeromonas or Bacillus sp. The oligosaccharide solution was spray dried or freeze dried to prepare a chitosan oligosaccharide antacid. The antacid test was performed about this antacid, and the result is shown in Table 1.

Example 3

The chitosan purified in Example 1 was dissolved by stirring with addition of an inorganic acid or an organic acid. The purified chitosan was digested at 37 to 50 ° C. for about 2 hours using a purified chitosan degrading enzyme, and the insoluble chitosan was removed after filtration. Herein, enzymes obtained using microorganisms of the genus Aeromonas or Bacillus sp. The solution was lyophilized to prepare a chitosan (water soluble chitosan) antacid. The antacid test was carried out for this antacid, and the results are shown in Table 1 below.

Comparative Example 1

After measuring the mass of N product (solid preparation) of I company which is currently commercially available, 500 mg was taken in a 200 ml flask according to the test method of Korean Pharmacopoeia, and 100 ml of 0.1 M HCl was added. After closing the stopper was shaken for 1 hour using a water bath shaker (37 ± 2 ℃), and then filtered using a simple filter paper. After the solution was cooled to room temperature, 50 ml of the filtrate was accurately taken, and an excess of HCl was titrated with 0.1 M NaOH (end point pH 3.5) to prepare a test formulation, followed by an antacid test. The results are shown in Table 1 below.

Comparative Example 2

Except for selecting 500mg of J product (solid formulation) commercially available from D company, 500 mg of the test formulation was prepared in the same manner as in Comparative Example 1, and then an antacid test was performed. The results are shown in Table 1 below.

Comparative Example 3

Accurately take 500mg of G company (liquid formulation) on the market, and place it in a 100ml volumetric flask according to the Korean Pharmacopoeia, and add 50ml of 0.2M HCl and 100ml with distilled water. Filled. After transferring to a 200ml flask, the residue was washed with 20ml of distilled water, and then the cap was closed and shaken for 1 hour using a water bath shaker (37 ± 2 ° C). Simple filtering using filter paper. After the solution was cooled to room temperature, 60 ml of the filtrate was accurately taken, and an excess of HCl was titrated with 0.1 M NaOH (end point pH 3.5) to prepare a test formulation, and an antacid test was performed. The results are shown in Table 1 below.

Antacid PH of the sample pH 3.5 pH 7.0 NaOH addition amount (ml) Antacid (ml) NaOH addition amount (ml) Antacid (ml) Example 1 1.53 36.0 51.7 47.3 9.5 Example 2 1.34 47.1 6.3 54.3 -18.5 Example 3 1.50 39.7 36.4 48.2 6.0 Comparative Example 1 1.63 19.3 183.5 32.9 103.8 Comparative Example 2 2.21 3.3 158.1 20.5 101.0 Comparative Example 3 1.56 46.5 188.5 50.4 -53.5

According to Table 1, the antacid power of N products (Comparative Example 1) of Company I, J products (Comparative Example 2) of Company D, and G products (Comparative Example 3) of Company B showed almost similar antagonistic ability. It can be seen. In the above test, the end point is defined as pH 3.5, but the calculation performance at the end point pH 7.0 was also compared. Solid formulations were similar for both products, but liquid formulations showed some differences and showed negative values. The chitosan formulation of Example 1 was found to be antacid but weak.

Although the degree of reaction varies from person to person, the antacid ability, or alkalinity, of current products on the market is evaluated to be excessive. Therefore, the alkalinity is so high that the side effects of metabolic alkylosis can not be ignored, and acid recoil may occur when taken for a long time. Can be. However, it can be seen that the chitin and chitosan antacids of the present invention have antacid ability, although less than about 30% of the prototypes.

Antacid formulations using chitin and / or chitosan of the present invention can minimize side effects due to taking antacids made by chemical synthesis, adsorption and removal of gastric acid made in the stomach, coating stomach walls or barriers, It acts as an environment- and bio-compatible antacid that can be expected to be treated and regenerated, and can achieve the effects of antacids, gastric wall protection, and immunity enhancement.

1 is a process for separating and purifying chitin in accordance with the present invention.

2 is a manufacturing process diagram of chitosan, chitosan salt (water-soluble chitosan), oligosaccharide, and monosaccharide according to the present invention.

Claims (3)

Made from crab, shrimp skin, squid bone, their extracts, chitin or chitosan, or containing polysaccharides such as sodium alginate, starch, mannose, cellulose, hyaluronic acid, agarose, galactomannan, agar, and carrageenan. Inflammatory, wound and antacids. A chitin or chitosan antacid in powder, tablet or liquid form, which contains chitin and chitosan, which are water-soluble substances prepared by chemical treatment or degrading enzyme, and chitosan, monosaccharide (glucosamine) or chitosan oligosaccharide. The method of claim 1 or 2, wherein the water-soluble substance chitin or chitosan, monosaccharides (glucosamine) or chitin and chitosan oligosaccharides are chitin N-acetyl-D-glucosamine or chitosan oligosaccharides have a glucosamine polymerization degree of 1 to 15 Chitin or chitosan antacid, characterized in that the decomposition as possible.