A preparation containing hydrotalcite and algal polysaccharide and its use

Abstract

The present invention relates to a preparation containing hydrotalcite and seaweed polysaccharide and its use, belonging to the technical field of drugs for digestive system diseases. The preparation containing hydrotalcite and seaweed polysaccharide of the present invention is composed of hydrotalcite, seaweed polysaccharide, amino acid, filler, disintegrant and lubricant. By combining hydrotalcite and seaweed polysaccharide, the present invention can achieve a more significant therapeutic effect, solve the problem of the decrease in acid-neutralizing capacity during the storage of the preparation, maintain the stability of the preparation, keep the drug effect and extend the shelf life.

Description

Technical Field

[0001] The present invention belongs to the technical field of drugs for digestive system diseases, and particularly relates to a preparation containing hydrotalcite and algal polysaccharide and its uses. Background Art

[0002] Disclosing the information of this background art section is only intended to enhance the understanding of the overall background of the present invention, and is not necessarily to be regarded as an admission or any form of implication that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] Digestive tract diseases, such as gastritis, gastric ulcer and colitis, etc., are common health problems worldwide and seriously affect the quality of life of patients. Current treatment methods include drug treatment and lifestyle adjustment. However, traditional drugs often have problems such as short-lasting efficacy and obvious side effects.

[0004] Hydrotalcite, as a commonly used antacid, has a significant effect of neutralizing gastric acid and can relieve gastric discomfort. Its molecular structure is arranged in a layered lattice and has various pharmacological effects: (1) Gastric acid neutralizing effect:; (2) Adsorption and binding effect; (3) Mucosal protection effect; (4) Promote the release of epidermal growth factor in the gastric mucosa, increase the content of phospholipids in the hydrophobic layer of the submucosa, and prevent gastric mucosal damage. Clinically, this product is used for gastric ulcer and duodenal ulcer; acute and chronic gastritis and duodenal ampullitis; reflux esophagitis; and symptomatic treatment of gastric discomfort related to excessive gastric acid, such as gastric burning pain, acid reflux, abdominal distension, nausea and vomiting, etc.

[0005] Algal polysaccharide is a mixture of multiple components, which is composed of different monosaccharide groups linked by glycosidic bonds and is the general term for various high-molecular carbohydrates contained between and within algal cells. Algal polysaccharide is an important polysaccharide substance with a wide variety and rich sources. It can not only improve the immune function of the body, but also has various biological activities such as anti-tumor, anti-virus, anti-radiation, lipid-lowering and anticoagulation.

[0006] Chinese Patent No. CN117919271A discloses a hydrotalcite tablet and its preparation method, which contains granule A and granule B. The granule A contains 50% of hydrotalcite and 4% - 8% of corn starch; the granule B contains 25% - 42% of fucoidan and 3% - 7% of corn starch. The prescription of the present invention contains fucoidan and adopts a dry granulation process. The prepared hydrotalcite tablet has excellent pharmaceutical properties and better clinical use effects.

[0007] The prior art discloses the preparation of a preparation by combining hydrotalcite and seaweed polysaccharides, which can achieve better clinical use effects. However, studies have found that the combination of hydrotalcite and seaweed polysaccharides reduces the stability of hydrotalcite during storage, and its acid-neutralizing capacity also significantly decreases.

[0008] Therefore, it is necessary to develop a pharmaceutical preparation that effectively combines hydrotalcite and seaweed polysaccharides, avoids the interaction between hydrotalcite and seaweed polysaccharides, and provides a new solution for the treatment of digestive tract diseases. Summary of the Invention

[0009] Combining hydrotalcite and seaweed polysaccharides can achieve more significant therapeutic effects. Hydrotalcite can neutralize gastric acid and reduce the damage of gastric acid to the gastric mucosa, while seaweed polysaccharides form an adhesion layer in the stomach, further protecting the gastric mucosa and potentially promoting the healing of the gastric mucosa. This combination drug strategy can not only improve the therapeutic effect but also potentially reduce the side effects of the drug. However, the common use of hydrotalcite and seaweed polysaccharides leads to the problem of decreased acid-neutralizing capacity during storage, affecting the drug efficacy. To overcome the deficiencies of the prior art, the present invention provides a preparation containing hydrotalcite and seaweed polysaccharides with stable acid-neutralizing capacity and qualified quality.

[0010] Specifically, the preparation containing hydrotalcite and seaweed polysaccharides is composed of the following components: 125-250 parts by weight of hydrotalcite, 50-150 parts by weight of seaweed polysaccharides (purchased from Sinuote Biology, with a content of 99%), 10-20 parts by weight of amino acids, 35-300 parts by weight of fillers, 10-30 parts by weight of disintegrants, and 5-15 parts by weight of lubricants; the amino acids are selected from one of lysine, arginine, and glutamic acid.

[0011] Furthermore, the filler is selected from at least one of starch, dextrin, microcrystalline cellulose, sucrose, lactose, mannitol, and pregelatinized starch; the disintegrant is selected from at least one of crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked carboxymethyl cellulose sodium; the lubricant is selected from at least one of colloidal silicon dioxide, magnesium stearate, and talc powder.

[0012] The present invention also provides a preparation method of the preparation containing hydrotalcite and seaweed polysaccharides, including the following steps:

[0013] a. The algal polysaccharide and amino acid are dissolved in 0.3 - 0.8 parts by weight of deionized water, mixed evenly, heated in a water bath at 45°C - 55°C for 20 min - 40 min, then rapidly cooled in a water bath at 5°C - 15°C, filtered by suction, the product is freeze-dried, pre-frozen at -35 ± 5°C for 1 - 3 h, heated to -15 ± 5°C and kept warm for 2 - 3 h, then heated to 10 ± 5°C and kept warm for 3 - 5 h, then cooled to -30 ± 5°C and kept warm for 1 - 3 h, the cold trap vacuum is opened, heated to -10 ± 5°C and kept for 5 - 10 h, then heated to 0 ± 5°C and kept for 3 - 5 h, and then heated to 30 ± 5°C and kept for 3 - 5 h to obtain the algal polysaccharide - amino acid complex;

[0014] b. Grind and sieve hydrotalcite, mix it with 1 / 4 - 1 / 2 of the lubricant, then add the algal polysaccharide - amino acid complex, mix evenly, add the disintegrant, filler, and the remaining lubricant, mix well, and press into tablets to obtain the product.

[0015] The present invention verifies the acid-neutralizing capacity of the above-mentioned preparation containing hydrotalcite and algal polysaccharide according to the measurement method of acid-neutralizing capacity in the Chinese Pharmacopoeia, and provides its use in the preparation of antacids.

[0016] Compared with the prior art, the technical effect of the present invention lies in:

[0017] The present invention cross-links algal polysaccharide with certain amino acids, which has better solubility, helps to improve the bioavailability of the drug in vivo, and enhances the therapeutic effect of the drug; enhances the stability of algal polysaccharide, making it less likely to degrade during storage and use; has better mechanical properties, with a certain elasticity, which can improve the stability and operability of solid drug preparations. After cross-linking and compounding algal polysaccharide and amino acid and then mixing with hydrotalcite to make a preparation, the problem of the decrease in acid-neutralizing capacity during the storage of the preparation is solved, the preparation can be maintained stable, the drug effect can be maintained, and the shelf life can be extended. Description of the Drawings

[0018] Figure 1 : Acid-neutralizing capacity of the tablets of Examples 1 - 3 and Comparative Examples 1 - 6. Detailed Embodiments

[0019] In order to make the objectives and technical solutions of the present invention clearer, the following examples are used to further illustrate the present invention. However, the protection scope of the present invention is not limited to these examples, and the examples are only used to explain the present invention. Those skilled in the art should understand that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0020] Example 1 Tablets Containing Hydrotalcite and Algal Polysaccharide (1000 tablets)

[0021] Formulation:

[0022]

[0023]

[0024] Preparation method:

[0025] a. The seaweed polysaccharide and amino acid are dissolved in 0.5 parts by weight of deionized water, mixed evenly, heated in a water bath at 50 °C for 30 min, then quickly cooled in a water bath at 10 °C, filtered by suction, the product is freeze-dried, pre-frozen at -35 °C for 2 h, heated to -15 °C and kept for 2.5 h, heated to 10 °C and kept for 4 h, then cooled to -30 °C and kept for 2 h, the cold trap is evacuated, heated to -10 °C and kept for 8 h, heated to 0 °C and then kept for 4 h, heated to 30 °C and kept for 4 h to obtain the seaweed polysaccharide-amino acid complex;

[0026] b. Grind and sieve hydrotalcite, mix it with 1 / 3 of the lubricant, then add the seaweed polysaccharide-amino acid complex, mix evenly, add the disintegrant, filler and the remaining lubricant, mix evenly, and press into tablets to obtain.

[0027] Example 2 Tablets Containing Hydrotalcite and Seaweed Polysaccharide (1000 tablets)

[0028] Formulation:

[0029]

[0030] Preparation method:

[0031] a. The seaweed polysaccharide and amino acid are dissolved in 0.8 parts by weight of deionized water, mixed evenly, heated in a water bath at 55 °C for 20 min, then quickly cooled in a water bath at 15 °C, filtered by suction, the product is freeze-dried, pre-frozen at -30 °C for 1 h, heated to -10 °C and kept for 2 h, heated to 5 °C and kept for 3 h, then cooled to -25 °C and kept for 1 h, the cold trap is evacuated, heated to -5 °C and kept for 5 h, heated to -5 °C and then kept for 3 h, heated to 25 °C and kept for 3 h to obtain the seaweed polysaccharide-amino acid complex;

[0032] b. Grind and sieve hydrotalcite, mix it with 1 / 2 of the lubricant, then add the seaweed polysaccharide-amino acid complex, mix evenly, add the disintegrant, filler and the remaining lubricant, mix evenly, and press into tablets to obtain.

[0033] Example 3 Tablets Containing Hydrotalcite and Seaweed Polysaccharide

[0034] Formulation:

[0035]

[0036] Preparation method:

[0037] a. The algal polysaccharide and amino acid are dissolved in 0.3 parts by weight of deionized water, mixed evenly, heated in a water bath at 45 °C for 40 min, then rapidly cooled in a water bath at 5 °C, filtered by suction, the product is freeze-dried, pre-frozen at -40 °C for 3 h, heated to -20 °C and kept for 3 h, then heated to 15 °C and kept for 5 h, and then cooled to -35 °C and kept for 3 h. The cold trap is evacuated, heated to -15 °C and kept for 10 h, then heated to 5 °C and kept for 5 h, and then heated to 35 °C and kept for 5 h to obtain the algal polysaccharide-amino acid complex;

[0038] b. Hydrotalcite is ground and sieved, mixed with 1 / 4 of the lubricant, then the algal polysaccharide-amino acid complex is added, mixed evenly, the disintegrant, filler and the remaining lubricant are added, mixed evenly, and then compressed into tablets to obtain the product.

[0039] Tablets containing hydrotalcite and algal polysaccharide in Examples 4-6

[0040] Formulation:

[0041]

[0042]

[0043] Preparation method: The same as that in Example 1.

[0044] Formulation of tablets containing hydrotalcite and algal polysaccharide in Examples 7-9:

[0045]

[0046] Preparation method: The same as that in Example 1.

[0047] Formulation of tablets containing hydrotalcite and algal polysaccharide in Examples 10-12:

[0048]

[0049]

[0050] Preparation method: The same as that in Example 1.

[0051] Tablets containing hydrotalcite and algal polysaccharide in Comparative Example 1 (1000 tablets)

[0052] Formulation:

[0053]

[0054] Preparation method:

[0055] a. The algal polysaccharide and amino acid are dissolved in 0.5 parts by weight of deionized water, mixed evenly, heated in a water bath at 50 °C for 30 min, then rapidly cooled in a water bath at 10 °C, filtered by suction, the product is freeze-dried, pre-frozen at -35 °C for 2 h, heated to -15 °C and kept for 2.5 h, heated to 10 °C and kept for 4 h, then cooled to -30 °C and kept for 2 h, the cold trap vacuum is opened, heated to -10 °C and kept for 8 h, heated to 0 °C and then kept for 4 h, heated to 30 °C and kept for 4 h, thus obtaining the algal polysaccharide-amino acid complex;

[0056] b. Grind and sieve hydrotalcite, mix it with 1 / 3 of the lubricant, then add the algal polysaccharide-amino acid complex, mix evenly, add the disintegrant, filler, and the remaining lubricant, mix well, and press into tablets to obtain the product.

[0057] Comparative Example 2 Tablets containing hydrotalcite and algal polysaccharide (1000 tablets)

[0058] Formulation:

[0059]

[0060] Preparation method:

[0061] a. The algal polysaccharide and amino acid are dissolved in 0.5 parts by weight of deionized water, mixed evenly, heated in a water bath at 50 °C for 30 min, then rapidly cooled in a water bath at 10 °C, filtered by suction, the product is freeze-dried, pre-frozen at -35 °C for 2 h, heated to -15 °C and kept for 2.5 h, heated to 10 °C and kept for 4 h, then cooled to -30 °C and kept for 2 h, the cold trap vacuum is opened, heated to -10 °C and kept for 8 h, heated to 0 °C and then kept for 4 h, heated to 30 °C and kept for 4 h, thus obtaining the algal polysaccharide-amino acid complex;

[0062] b. Grind and sieve hydrotalcite, mix it with 1 / 3 of the lubricant, then add the algal polysaccharide-amino acid complex, mix evenly, add the disintegrant, filler, and the remaining lubricant, mix well, and press into tablets to obtain the product.

[0063] Comparative Example 3 Tablets containing hydrotalcite and algal polysaccharide (1000 tablets)

[0064] Formulation:

[0065]

[0066]

[0067] Preparation method:

[0068] a. The algal polysaccharide and amino acid are dissolved in 0.5 parts by weight of deionized water, mixed evenly, heated in a water bath at 50 °C for 30 min, then quickly cooled in a water bath at 10 °C, filtered by suction, and dried to obtain the algal polysaccharide-amino acid complex;

[0069] b. Hydrotalcite is ground, sieved, mixed with 1 / 3 of the lubricant, then the algal polysaccharide-amino acid complex is added, mixed evenly, the disintegrant, filler, and the remaining lubricant are added, mixed evenly, and pressed into tablets to obtain the product.

[0070] Control Example 4 Tablets containing hydrotalcite and algal polysaccharide (1000 tablets)

[0071] Formulation:

[0072]

[0073] Preparation method:

[0074] a. The algal polysaccharide and amino acid are dissolved in 0.5 parts by weight of deionized water, mixed evenly, heated in a water bath at 50 °C for 30 min, then quickly cooled in a water bath at 10 °C, filtered by suction, and the product is freeze-dried, pre-frozen at -35 °C, the cold trap is evacuated, the temperature is raised to -10 °C and maintained for 8 h, then the temperature is raised to 0 °C and maintained for 4 h, and then the temperature is raised to 30 °C and maintained for 4 h to obtain the algal polysaccharide-amino acid complex;

[0075] b. Hydrotalcite is ground, sieved, mixed with 1 / 3 of the lubricant, then the algal polysaccharide-amino acid complex is added, mixed evenly, the disintegrant, filler, and the remaining lubricant are added, mixed evenly, and pressed into tablets to obtain the product.

[0076] Control Example 5 Tablets containing hydrotalcite and algal polysaccharide (1000 tablets)

[0077] Formulation:

[0078]

[0079] Preparation method:

[0080] a. The algal polysaccharide is mixed with 1 / 2 of the filler and disintegrant, and dry granulation is carried out to prepare algal polysaccharide granules;

[0081] b. Hydrotalcite is mixed with the remaining filler and disintegrant, and dry granulation is carried out to prepare hydrotalcite granules;

[0082] c. The algal polysaccharide granules and hydrotalcite granules are mixed, the lubricant is added, and pressed into tablets to obtain the product.

[0083] Control Example 6 Hydrotalcite Tablets (National Medicine Approval Number H50021189)

[0084] Examples 1-12 and Comparative Examples 1-6 were packaged according to the commercial packaging and subjected to an accelerated test at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%. Samples were taken on the 1st day, the end of the 2nd month, the end of the 3rd month, and the end of the 6th month for testing.

[0085] Determination of acid-neutralizing capacity

[0086] According to the method specified in the Chinese Pharmacopoeia, the test sample was accurately weighed and placed in a 250 ml beaker. A small amount of water was added to form a homogeneous paste, and then water was slowly added to 100 ml. Exactly 100 ml of hydrochloric acid titrant (0.1 mol / L) was added precisely. It was stirred at a speed of 200 revolutions per minute for 1 hour under the condition of maintaining the temperature at 37°C. After cooling, it was titrated with sodium hydroxide titrant (0.1 mol / L) until the pH value reached 3.5. The amount of hydrochloric acid titrant (0.1 mol / L) consumed by every 1 g of hydrotalcite should not be less than 260 ml.

[0087] Table 1 Rate of decrease in acid-neutralizing capacity

[0088]

[0089]

[0090] Figure 1 Regarding the acid-neutralizing capacity of the preparations of Examples 1-3 and Comparative Examples 1-6, the tablets containing hydrotalcite and seaweed polysaccharide in Examples 1-3 of the present invention have strong acid-neutralizing capacity and more excellent anti-acid effect. The statistics in Table 1 show that after the present invention combines seaweed polysaccharide with certain amino acids to form a complex, the phenomenon that the acid-neutralizing capacity of hydrotalcite decreases due to the reaction between seaweed polysaccharide and hydrotalcite is avoided, and even the stability of hydrotalcite is improved. The rate of decrease in acid-neutralizing capacity of the preparations obtained in Examples 1-3 is less than that of the commercially available preparation in Comparative Example 6, which is beneficial to extending the shelf life of the preparation.

[0091] Table 2 Acid-neutralizing capacity of the tablets containing hydrotalcite and seaweed polysaccharide in Examples 4-12

[0092]

[0093] The acid-neutralizing capacity of the tablets containing hydrotalcite and seaweed polysaccharide in Examples 4-12 shown in Table 2 indicates that after the present invention prepares a complex of seaweed polysaccharide with lysine, arginine, and glutamic acid in a certain proportion, it can improve the acid-neutralizing ability of hydrotalcite and maintain excellent acid-neutralizing capacity during the accelerated test, thereby enhancing its stability.

[0094] Quality inspection of the tablets of Examples 1-12 and Comparative Examples 1-5

[0095] Table 3 Quality evaluation of the tablets of Examples 1-12 and Comparative Examples 1-5

[0096]

[0097]

[0098] Table 3 shows the hardness, friability, disintegration time limit, and dissolution rate of the tablets of Examples 1 to 12 and Comparative Examples 1 to 5 obtained by statistics. The tablets containing hydrotalcite and algal polysaccharides in Examples 1 to 12 of the present invention have appropriate hardness, low friability, appropriate disintegration time, and high dissolution rate, can maintain durability during transportation, and have excellent bioavailability and onset speed.

Claims

1. A preparation containing hydrotalcite and seaweed polysaccharide, characterized in that, The preparation containing hydrotalcite and seaweed polysaccharide consists of the following components: 125 - 250 parts by weight of hydrotalcite, 50 - 150 parts by weight of seaweed polysaccharide, 10 - 20 parts by weight of amino acid, 35 - 300 parts by weight of filler, 10 - 30 parts by weight of disintegrant, 5 - 15 parts by weight of lubricant; the amino acid is selected from one of lysine, arginine, and glutamic acid; The preparation method of the preparation containing hydrotalcite and seaweed polysaccharide comprises the following steps: a. The seaweed polysaccharide and amino acid are dissolved in 0.3 - 0.8 times the weight of deionized water, mixed evenly, heated in a water bath at 45°C - 55°C for 20 min - 40 min, then rapidly cooled in a water bath at 5°C - 15°C, filtered by suction, and the product is freeze-dried to obtain the seaweed polysaccharide-amino acid complex; b. Grind and sieve the hydrotalcite, mix it with 1 / 4 - 1 / 2 of the lubricant, then add the seaweed polysaccharide-amino acid complex, mix evenly, add the disintegrant, filler, and the remaining lubricant, mix evenly, and press into tablets to obtain; The freeze-drying procedure is as follows: Pre-freeze at -35 ± 5°C for 1 - 3 h, warm up to -15 ± 5°C and keep warm for 2 - 3 h, warm up to 10 ± 5°C and keep warm for 3 - 5 h, then cool down to -30 ± 5°C and keep warm for 1 - 3 h, turn on the cold trap vacuum, warm up to -10 ± 5°C and keep for 5 - 10 h, warm up to 0 ± 5°C, then keep for 3 - 5 h, and warm up to 30 ± 5°C and keep for 3 - 5 h.

2. The preparation containing hydrotalcite and algal polysaccharide according to claim 1, characterized in that, The filler is selected from at least one of starch, dextrin, microcrystalline cellulose, sucrose, lactose, mannitol, and pregelatinized starch.

3. The preparation containing hydrotalcite and seaweed polysaccharide according to claim 1, characterized in that, The disintegrant is selected from at least one of crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked carboxymethyl cellulose sodium.

4. The preparation containing hydrotalcite and algal polysaccharide according to claim 1, wherein The lubricant is selected from at least one of colloidal silicon dioxide, magnesium stearate, and talc powder.

5. The preparation containing hydrotalcite and fucoidan according to claim 1 or 2, characterized in that, The filler is starch, dextrin, and lactose.

6. The preparation containing hydrotalcite and seaweed polysaccharide according to claim 1 or 3, characterized in that, The disintegrant is low-substituted hydroxypropyl cellulose.

7. The preparation containing hydrotalcite and algal polysaccharide according to claim 1 or 4, characterized in that, The lubricant is magnesium stearate.

8. Use of the preparation containing hydrotalcite and seaweed polysaccharide according to claim 1 in the preparation of antacids.

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