Preparation containing hydrotalcite and algal polysaccharides and application thereof

Abstract

The invention relates to a preparation containing hydrotalcite and algal polysaccharides and application of the preparation, and belongs to the technical field of medicines for treating digestive system diseases. The preparation containing hydrotalcite and algal polysaccharides is composed of hydrotalcite, algal polysaccharides, amino acids, a filler, a disintegrating agent and a lubricant. According to the invention, hydrotalcite and algal polysaccharides are combined for use, so that a more remarkable treatment effect can be realized, the problem that the acid-making capacity of the preparation is reduced in the storage process is solved, the stability of the preparation can be maintained, the drug effect is kept, and the shelf life is prolonged.

Description

Technical Field

[0001] The invention belongs to the technical field of drugs for digestive system diseases, and specifically relates to a preparation containing hydrotalcite and seaweed polysaccharide and a use thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Digestive tract diseases, such as gastritis, gastric ulcers and colitis, are common health problems worldwide, seriously affecting the quality of life of patients. Current treatments include medication and lifestyle adjustments, however, traditional drugs often have problems such as short-term efficacy and significant side effects.

[0004] As a commonly used antacid, aluminum carbonate has a significant effect in neutralizing gastric acid and relieving stomach discomfort. Its molecular structure is arranged in a layered lattice and has multiple pharmacological effects: (1) gastric acid neutralization; (2) adsorption and binding effects; (3) mucosal protection; (4) promoting the release of epidermal growth factor in the gastric mucosa, increasing the content of phospholipids in the hydrophobic layer under the mucus, and preventing gastric mucosal damage. Clinically, this product is used for gastric ulcers and duodenal ulcers; acute and chronic gastritis and duodenal ampulla inflammation; reflux esophagitis; and for symptomatic treatment of stomach discomfort related to excessive gastric acid, such as heartburn, acid reflux, abdominal distension, nausea and vomiting.

[0005] Algae polysaccharides are a type of multi-component mixture composed of different monosaccharides connected by glycosidic bonds. It is a general term for various high-molecular carbohydrates contained between and within algae cells. Algae polysaccharides are important polysaccharide substances with a wide variety and abundant sources. They can not only enhance the body's immune function, but also have multiple biological activities such as anti-tumor, anti-viral, anti-radiation, lipid-lowering and anti-coagulation.

[0006] The Chinese patent with publication number CN117919271A discloses a hydrotalcite tablet and a preparation method thereof, comprising particles A and particles B, wherein the particles A contain 50% hydrotalcite and 4% to 8% corn starch; and the particles B contain 25% to 42% fucoidan and 3% to 7% corn starch. The prescription of the present invention contains fucoidan and adopts a dry granulation process, so that the hydrotalcite tablet has excellent pharmaceutical properties and better clinical use effect.

[0007] The prior art discloses that the combined use of aluminum carbonate and seaweed polysaccharides to prepare a preparation can achieve better clinical results. However, studies have found that the combined use of aluminum carbonate and seaweed polysaccharides reduces the stability of aluminum carbonate during storage, and its acid-reducing ability also decreases significantly.

[0008] Therefore, it is necessary to develop a pharmaceutical preparation that effectively combines aluminum carbonate with seaweed polysaccharides to avoid the interaction between aluminum carbonate and seaweed polysaccharides and provide a new solution for the treatment of gastrointestinal diseases. Summary of the invention

[0009] The combined use of aluminum carbonate and seaweed polysaccharide can achieve a more significant therapeutic effect. Aluminum carbonate can neutralize gastric acid and reduce the damage of gastric acid to the gastric mucosa, while seaweed polysaccharide forms an adhesion layer in the stomach, further protecting the gastric mucosa and possibly promoting the healing of the gastric mucosa. This combination drug strategy can not only improve the therapeutic effect, but also reduce the side effects of the drug. However, the use of aluminum carbonate and seaweed polysaccharide together will lead to the problem of decreased antacidity during storage, affecting the efficacy of the drug. To overcome the shortcomings of the prior art, the present invention provides a preparation containing aluminum carbonate and seaweed polysaccharide with stable antacidity and qualified quality.

[0010] Specifically, the preparation containing aluminum carbonate and seaweed polysaccharide is composed of the following components: 125-250 parts by weight of aluminum carbonate, 50-150 parts by weight of seaweed polysaccharide (purchased from Snort Biotechnology, content 99%), 10-20 parts by weight of amino acid, 35-300 parts by weight of filler, 10-30 parts by weight of disintegrant, and 5-15 parts by weight of lubricant; the amino acid is 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 cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose; and the lubricant is selected from at least one of micro-powdered silica gel, magnesium stearate, and talc.

[0012] The present invention also provides a method for preparing a preparation containing hydrotalcite and seaweed polysaccharide, comprising the following steps:

[0013] a. Dissolve seaweed polysaccharides and amino acids in 0.3 to 0.8 times the weight of deionized water, mix well, heat in a water bath at 45°C to 55°C for 20min to 40min, and then quickly cool in a water bath at 5°C to 15°C, filter, freeze-dry the product, pre-freeze at -35±5°C, keep for 1 to 3h, heat to -15±5°C, keep warm for 2 to 3h, heat to 10±5°C, keep warm for 3 to 5h, cool to -30±5°C and keep warm for 1 to 3h, open the cold trap vacuum, heat to -10±5°C, keep for 5 to 10h, heat to 0±5°C, then keep for 3 to 5h, heat to 30±5°C, keep for 3 to 5h, and obtain seaweed polysaccharide-amino acid complex;

[0014] b. Grind and sieve aluminum carbonate, mix with 1 / 4 to 1 / 2 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0015] The present invention verifies the antacidity of the preparation containing aluminum magnesium carbonate and seaweed polysaccharide according to the antacidity measurement method in the Chinese Pharmacopoeia, and provides its use in the preparation of antacids.

[0016] Compared with the prior art, the technical effects of the present invention are:

[0017] The present invention cross-links seaweed polysaccharides with certain amino acids, which has better solubility, helps to improve the bioavailability of drugs in the body, and enhances the therapeutic effect of drugs; enhances the stability of seaweed polysaccharides, making them less prone to degradation during storage and use; has better mechanical properties, has a certain elasticity, and can improve the stability and operability of solid drug preparations. The seaweed polysaccharide-amino acid cross-linked composite is then mixed with aluminum magnesium carbonate to prepare a preparation, which solves the problem of decreased acid resistance during storage of the preparation, can maintain the stability of the preparation, maintain the efficacy, and extend the shelf life. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 : The antacidity of the tablets of Examples 1 to 3 and Comparative Examples 1 to 6. DETAILED DESCRIPTION

[0019] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art 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 seaweed polysaccharide (1000 tablets)

[0021] formula:

[0022]

[0023]

[0024] Preparation method:

[0025] a. Dissolve seaweed polysaccharides and amino acids in 0.5 times the weight of deionized water, mix well, heat in a 50°C water bath for 30 minutes, then quickly cool in a 10°C water bath, filter, freeze-dry the product, pre-freeze at -35°C, keep for 2 hours, heat to -15°C, keep for 2.5 hours, heat to 10°C, keep for 4 hours, cool to -30°C and keep for 2 hours, open the cold trap vacuum, heat to -10°C, keep for 8 hours, heat to 0°C, then keep for 4 hours, heat to 30°C, keep for 4 hours, and obtain seaweed polysaccharide-amino acid complex;

[0026] b. Grind and sieve aluminum carbonate, mix with 1 / 3 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0027] Example 2 Tablets containing hydrotalcite and seaweed polysaccharide (1000 tablets)

[0028] formula:

[0029]

[0030] Preparation method:

[0031] a. Dissolve seaweed polysaccharides and amino acids in 0.8 times the weight of deionized water, mix well, heat in a 55°C water bath for 20 min, then quickly cool in a 15°C water bath, filter, freeze-dry the product, pre-freeze at -30°C, keep for 1 h, warm to -10°C, keep for 2 h, warm to 5°C, keep for 3 h, cool to -25°C and keep for 1 h, open the cold trap vacuum, warm to -5°C, keep for 5 h, warm to -5°C, then keep for 3 h, warm to 25°C, keep for 3 h, and obtain seaweed polysaccharide-amino acid complex;

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

[0033] Example 3 Tablets containing hydrotalcite and seaweed polysaccharide

[0034] formula:

[0035]

[0036] Preparation method:

[0037] a. Dissolve seaweed polysaccharides and amino acids in 0.3 parts by weight of deionized water, mix well, heat in a 45°C water bath for 40 min, then quickly cool in a 5°C water bath, filter, freeze-dry the product, pre-freeze at -40°C, keep for 3 h, heat to -20°C, keep for 3 h, heat to 15°C, keep for 5 h, cool to -35°C and keep for 3 h, open the cold trap vacuum, heat to -15°C, keep for 10 h, heat to 5°C, then keep for 5 h, heat to 35°C, keep for 5 h, and obtain seaweed polysaccharide-amino acid complex;

[0038] b. Grind and sieve aluminum carbonate, mix with 1 / 4 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0039] Examples 4 to 6 Tablets containing hydrotalcite and seaweed polysaccharide

[0040] formula:

[0041]

[0042]

[0043] Preparation method: Same as Example 1.

[0044] Examples 7 to 9: Tablet formulations containing hydrotalcite and seaweed polysaccharide:

[0045]

[0046] Preparation method: Same as Example 1.

[0047] Embodiments 10-12 Formulation of tablets containing hydrotalcite and seaweed polysaccharide:

[0048]

[0049]

[0050] Preparation method: Same as Example 1.

[0051] Comparative Example 1 Tablets containing aluminum carbonate magnesium and seaweed polysaccharide (1000 tablets)

[0052] formula:

[0053]

[0054] Preparation method:

[0055] a. Dissolve seaweed polysaccharides and amino acids in 0.5 times the weight of deionized water, mix well, heat in a 50°C water bath for 30 minutes, then quickly cool in a 10°C water bath, filter, freeze-dry the product, pre-freeze at -35°C, keep for 2 hours, heat to -15°C, keep for 2.5 hours, heat to 10°C, keep for 4 hours, cool to -30°C and keep for 2 hours, open the cold trap vacuum, heat to -10°C, keep for 8 hours, heat to 0°C, then keep for 4 hours, heat to 30°C, keep for 4 hours, and obtain seaweed polysaccharide-amino acid complex;

[0056] b. Grind and sieve aluminum carbonate, mix with 1 / 3 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0057] Comparative Example 2 Tablets containing aluminum carbonate magnesium and seaweed polysaccharide (1000 tablets)

[0058] formula:

[0059]

[0060] Preparation method:

[0061] a. Dissolve seaweed polysaccharides and amino acids in 0.5 times the weight of deionized water, mix well, heat in a 50°C water bath for 30 minutes, then quickly cool in a 10°C water bath, filter, freeze-dry the product, pre-freeze at -35°C, keep for 2 hours, heat to -15°C, keep for 2.5 hours, heat to 10°C, keep for 4 hours, cool to -30°C and keep for 2 hours, open the cold trap vacuum, heat to -10°C, keep for 8 hours, heat to 0°C, then keep for 4 hours, heat to 30°C, keep for 4 hours, and obtain seaweed polysaccharide-amino acid complex;

[0062] b. Grind and sieve aluminum carbonate, mix with 1 / 3 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0063] Comparative Example 3 Tablets containing aluminum carbonate magnesium and seaweed polysaccharide (1000 tablets)

[0064] formula:

[0065]

[0066]

[0067] Preparation method:

[0068] a. Dissolve seaweed polysaccharides and amino acids in 0.5 parts by weight of deionized water, mix well, heat in a 50°C water bath for 30 minutes, and then quickly cool in a 10°C water bath, filter, and dry to obtain a seaweed polysaccharide-amino acid complex;

[0069] b. Grind and sieve aluminum carbonate, mix with 1 / 3 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0070] Comparative Example 4 Tablets containing aluminum carbonate magnesium and seaweed polysaccharide (1000 tablets)

[0071] formula:

[0072]

[0073] Preparation method:

[0074] a. Dissolve seaweed polysaccharides and amino acids in 0.5 parts by weight of deionized water, mix well, heat in a 50°C water bath for 30 min, and then quickly cool in a 10°C water bath, filter, freeze-dry the product, pre-freeze at -35°C, open the cold trap vacuum, heat to -10°C, keep for 8h, heat to 0°C, then keep for 4h, heat to 30°C, keep for 4h, and obtain seaweed polysaccharide-amino acid complex;

[0075] b. Grind and sieve aluminum carbonate, mix with 1 / 3 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

[0076] Comparative Example 5 Tablets containing aluminum carbonate magnesium and seaweed polysaccharide (1000 tablets)

[0077] formula:

[0078]

[0079] Preparation method:

[0080] a. Mix seaweed polysaccharide with 1 / 2 filler and disintegrant, and dry granulate to make seaweed polysaccharide granules;

[0081] b. Hydrotalcite is mixed with the remaining filler and disintegrant, and dry granulated to form hydrotalcite particles;

[0082] c. Mix the seaweed polysaccharide particles with aluminum magnesium carbonate particles, add a lubricant, and press into tablets to obtain the product.

[0083] Comparative Example 6 Aluminum carbonate tablets (National Medicine Standard H50021189)

[0084] Examples 1 to 12 and Comparative Examples 1 to 6 were packaged as sold commercially and subjected to accelerated testing at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%. Samples were taken at the first day, the end of the second month, the end of the third month, and the end of the sixth month for testing.

[0085] Determination of acidity

[0086] According to the method specified in the "Chinese Pharmacopoeia", take the test sample and weigh it accurately, put it in a 250ml beaker, add a small amount of water to make a uniform paste, slowly add water to 100ml, accurately add 100ml of hydrochloric acid titration solution (0.1mol / L), stir at 200 revolutions per minute at 37℃ for 1 hour, cool, and titrate with sodium hydroxide titration solution (0.1mol / L) to pH 3.5. For every 1g of aluminum carbonate magnesium, the consumption of hydrochloric acid titration solution (0.1mol / L) shall not be less than 260ml.

[0087] Table 1 Decrease rate of acid-reducing capacity

[0088]

[0089]

[0090] Figure 1 The antacidity of the preparations of Examples 1 to 3 and Comparative Examples 1 to 6 is shown in Table 1. The tablets containing hydrotalcite and seaweed polysaccharide of Examples 1 to 3 of the present invention have strong antacidity and better anti-acid effect. Table 1 shows that after the present invention combines seaweed polysaccharide with certain amino acids to form a complex, the phenomenon of the decrease in the antacidity of hydrotalcite caused by the reaction of seaweed polysaccharide with hydrotalcite is avoided, and the stability of hydrotalcite is even improved. The antacidity decrease rate of the preparations prepared in Examples 1 to 3 is less than that of the commercial preparation of Comparative Example 6, which is beneficial to extend the shelf life of the preparations.

[0091] Table 2: Acid resistance of tablets containing hydrotalcite and seaweed polysaccharide in Examples 4 to 12

[0092]

[0093] The antacidity of the tablets containing aluminum carbonate and seaweed polysaccharide in Table 2 Examples 4 to 12 shows that after the present invention prepares seaweed polysaccharide into a complex with lysine, arginine and glutamic acid in a certain proportion, the acid-reducing ability of aluminum carbonate can be improved, and the excellent acid-reducing ability can be maintained in the accelerated test, thereby improving its stability.

[0094] Quality test of tablets of Examples 1 to 12 and Comparative Examples 1 to 5

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

[0096]

[0097]

[0098] Table 3 statistically obtains the hardness, friability, disintegration time and solubility of the tablets of Examples 1 to 12 and Comparative Examples 1 to 5. The tablets containing aluminum magnesium carbonate and seaweed polysaccharide of Examples 1 to 12 of the present invention have appropriate hardness, low friability, appropriate disintegration time, high solubility, 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 is composed 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, and 5-15 parts by weight of lubricant; the amino acid is selected from one of lysine, arginine, and glutamic acid.

2. The preparation containing hydrotalcite and seaweed 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 cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked sodium carboxymethyl cellulose.

4. The preparation containing hydrotalcite and seaweed polysaccharide according to claim 1, characterized in that: The lubricant is selected from at least one of micro powder silica gel, magnesium stearate and talc.

5. The preparation containing hydrotalcite and seaweed polysaccharide according to claim 1 or 2, characterized in that: The filler is starch, dextrin or 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 seaweed polysaccharide according to claim 1 or 4, characterized in that: The lubricant is magnesium stearate.

8. A method for preparing the preparation containing hydrotalcite and seaweed polysaccharide according to claim 1, characterized in that: The preparation method comprises the following steps: a. Dissolve seaweed polysaccharides and amino acids in 0.3 to 0.8 times the weight of deionized water, mix well, heat in a water bath at 45°C to 55°C for 20min to 40min, and then quickly cool in a water bath at 5°C to 15°C, filter, and freeze-dry the product to obtain a seaweed polysaccharide-amino acid complex; b. Grind and sieve aluminum carbonate, mix with 1 / 4 to 1 / 2 of lubricant, add seaweed polysaccharide-amino acid complex, mix evenly, add disintegrant, filler, remaining lubricant, mix evenly, and tablet.

9. The preparation method according to claim 8, characterized in that: The freeze drying procedure is: Pre-freeze at -35±5℃, keep for 1~3h, heat up to -15±5℃, keep warm for 2~3h, heat up to 10±5℃, keep warm for 3~5h, cool down to -30±5℃ and keep warm for 1~3h, open the cold trap vacuum, heat up to -10±5℃, keep for 5~10h, heat up to 0±5℃, then keep for 3~5h, heat up to 30±5℃, keep for 3~5h.

10. Use of the preparation containing aluminum carbonate magnesium and seaweed polysaccharide according to claim 1 in the preparation of antacids.

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