Graded preparation of high-purity GG sodium alginate plant-based enteric capsule and method
Through grading treatment, high-purity GG chain segment sodium alginate was extracted, and combined with calcium water spraying and film forming technology, high-purity GG plant-based enteric-coated capsules with dense structure, good acid resistance, high mechanical strength and excellent sustained release effect were prepared, solving the problems of poor mechanical strength, poor stability and poor disintegration effect in the prior art.
Patent Information
- Application Number
- CN202510333733.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-20
- Publication Date
- 2025-05-13
Smart Images
Figure BDA0005321112370000091
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biology and new medicine technology, and specifically relates to a method and application of a graded preparation method of high-purity GG sodium alginate plant-based enteric capsule. Background Art
[0002] With the development of society and the advancement of pharmaceutical technology, the development of pharmaceutical carrier capsules has attracted more and more attention. Traditional pharmaceutical carrier capsules are generally gelatin capsules, but they have problems such as temperature and humidity sensitivity and animal origin, which affect their further use. Therefore, researchers have strengthened the exploration of new capsule materials. Enteric-coated capsules are a special type of capsule among pharmaceutical carrier capsules. They are insoluble in the stomach and released in the intestines. The traditional enteric-coated capsule process is complicated and costly, and other unnecessary chemicals are introduced. Therefore, sodium alginate plant-based enteric-coated capsules came into being.
[0003] Alginate and alginates are mainly polysaccharides extracted from brown algae, such as giant kelp, kelp, and kombu. They are composed of guluronic acid (G) and mannuronic acid (M). Sodium alginate can also form thermally irreversible gels with divalent or higher metal ions. Therefore, it has many advantages in biocompatibility and non-toxicity, and has unique applications in food, chemical industry, and medicine.
[0004] The specifications of medicinal alginate are strictly required, but the existing plant-based enteric-coated sodium alginate capsules have poor mechanical strength, poor stability, and poor disintegration effect, which affects their widespread use. Among them, the main reason affecting its performance is the low content of guluronic acid (G) in sodium alginate. The higher the content of the GG segment of sodium alginate, the stronger the mechanical strength, better the stability, and better the disintegration effect of the prepared capsules. Therefore, the extraction of high-purity GG sodium alginate becomes the key. Summary of the invention
[0005] In view of the shortcomings and deficiencies in the prior art, the present invention provides a method and method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded preparation, which have compact structure, good acid resistance stability, high mechanical strength and excellent sustained-release effect.
[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions:
[0007] The present invention provides a method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method, which is characterized by comprising the following steps: adding sodium alginate granules to a potassium salt and magnesium salt mixed solution for dissolution, and extracting high-purity GG chain segment sodium alginate by graded treatment; and then using the high-purity GG chain segment sodium alginate to prepare high-purity GG plant-based enteric capsules;
[0008] The concentration of the potassium salt and magnesium salt mixed solution is 3%-30%, and the ratio of potassium salt to magnesium salt is 9:1-5:5. The weight ratio of the sodium alginate granules to the potassium salt and magnesium salt mixed solution is 1%-15%.
[0009] Preferably, the steps include:
[0010] S1, adding sodium alginate to a mixed solution of potassium salt and magnesium salt to dissolve, extracting high-purity GG segments by graded treatment, taking the supernatant by centrifugation, and then drying by alcohol precipitation to obtain high-purity GG sodium alginate;
[0011] S2, adding the high-purity GG sodium alginate prepared in step S1 into deionized water, and adding calcium salt and glycerol, and mixing under vacuum to form a sol, and then performing a rubber refining process, and vacuum degassing;
[0012] S3, adding lactone to adjust the pH and form microgel particles;
[0013] S4, subjecting the microgel particles formed in step S3 to a film forming process;
[0014] S5. Finally, the mold is sprayed with calcium water and dried to obtain high-purity GG plant-based enteric capsules.
[0015] Preferably, in step S1, the sodium alginate is derived from one or more of kelp, giant kelp, ascophyllum, sargassum, and bark algae;
[0016] Sodium alginate is a medical grade sodium alginate finished granular gel, the viscosity of sodium alginate is less than or equal to 80mpas, and the solubility concentration is 1%-15%.
[0017] Preferably, in step S1, in the potassium salt and magnesium salt mixed solution, the potassium salt is one or both of potassium citrate and potassium chloride; the magnesium salt is one or both of magnesium chloride and magnesium citrate.
[0018] Preferably, in step S2, the weight ratio of the added amount of deionized water and high-purity GG sodium alginate in the sol is: deionized water: high-purity GG sodium alginate = 5-10:1;
[0019] The calcium salt is calcium carbonate, and its dosage is 0.1%-0.3% of the weight of the sol; the dosage of glycerol is 1%-3% of the weight of the sol.
[0020] Preferably, in step S2, the specific conditions for the rubber mixing treatment are: a temperature of 40°C-80°C, a heat preservation reaction time of 30min-60min, and a subsequent vacuum degassing.
[0021] Preferably, in step S3, the lactone is glucuronic acid lactone, the pH is adjusted to 4-6, and the amount thereof is 0.1%-0.5% of the weight of the sol.
[0022] Preferably, in step S4, before the film forming, a layer of glycerin needs to be coated in the corresponding film forming mold; in step S5, the concentration of calcium water used in the calcium water spraying operation is 0.1%-1%.
[0023] The method for preparing high-purity GG sodium alginate by fractionation comprises the following steps: adding sodium alginate granule gel to a potassium salt and magnesium salt mixed solution to dissolve, and extracting high-purity GG chain segment sodium alginate by fractionation treatment;
[0024] The concentration of the potassium salt and magnesium salt mixed solution is 3%-30%, and the ratio of potassium salt to magnesium salt is 9:1-5:5.
[0025] The high-purity GG sodium alginate plant-based enteric capsules are prepared by fractionation, and are prepared according to the above-mentioned method for preparing high-purity GG sodium alginate plant-based enteric capsules by fractionation.
[0026] The present invention provides a graded preparation method of high-purity GG sodium alginate plant-based enteric capsules, which has the following beneficial effects:
[0027] (1) The present invention provides a method and method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded treatment, wherein pharmaceutical-grade sodium alginate is graded through a potassium salt and magnesium salt mixed solution to obtain high-purity GG segment sodium alginate, wherein a special concentration ratio of potassium salt and magnesium salt is used for synergistic effect, wherein potassium salt dissolves the GG segment and precipitates other segments, while magnesium salt precipitates the GG segment and dissolves other segments, so high-purity GG segment sodium alginate is obtained by controlling the proportion of potassium salt and magnesium salt in the potassium salt and magnesium salt mixed solution.
[0028] At the same time, the high-purity GG sodium alginate plant-based enteric capsules prepared by the present invention are based on high-purity GG segment sodium alginate. The prepared sodium alginate plant-based enteric capsules have dense structure, good acid resistance and stability, high mechanical strength, and excellent sustained-release effect, and can be widely used in the fields of biology and new medical technology.
[0029] Moreover, the remaining MM and GM segments after sodium alginate classification can be applied in other related technical fields, effectively improving product production utilization and complying with the concept of green environmental protection.
[0030] (2) In the method of the present invention, calcium carbonate and glucuronide are added during the sol formation to form microgel particles by in-situ gelation, thereby significantly improving the capsule strength.
[0031] Glucuronolactone is added to adjust the pH value of the glue. While releasing calcium ions, it makes the fluidity of sodium alginate worse in a low pH environment, increases the viscosity, makes it more suitable for compression molding process, and facilitates better calcification molding in the later stage.
[0032] In the later stage, calcium water is sprayed to form an osmotic gel, and combined with the in-situ gel of the previous process, the mechanical strength, toughness and disintegration stability of the capsule shell are significantly enhanced by using a double-layer gel method. DETAILED DESCRIPTION
[0033] The terms used in the present invention, unless otherwise specified, generally have the meanings commonly understood by those of ordinary skill in the art. The present invention will be further described in detail below in conjunction with specific examples and with reference to data. The following examples are intended to illustrate the present invention and are not intended to limit the scope of the present invention in any way.
[0034] Example 1
[0035] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method of the present invention comprises the following steps:
[0036] S1 adds medical grade sodium alginate granules extracted from giant kelp LN with a viscosity of 50 mpas to a mixture of potassium chloride and magnesium chloride with a concentration of 15% for dissolution and classification, wherein the weight ratio of potassium salt to magnesium salt is 9:1, and the sodium alginate granules account for 7% of the mixed solution. After graded precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain high-purity GG segment sodium alginate, with the GG segment content accounting for 65%.
[0037] S2: dissolving the high-purity GG sodium alginate prepared in step S1 in deionized water to prepare a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to prepare a sol solution; wherein the weight ratio of deionized water and high-purity GG sodium alginate added to the sol is deionized water: high-purity GG sodium alginate = 7:1.
[0038] S3 refines the sol solution prepared in S2 at 50° C. for 40 minutes and then performs vacuum degassing.
[0039] S4: adding glucurone to the S3 glue solution, the amount of which is 0.2% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0040] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.3%, and then dried to obtain high-purity GG sodium alginate plant-based enteric capsules.
[0041] Example 2
[0042] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method of the present invention comprises the following steps:
[0043] S1 adds medical grade sodium alginate granules extracted from giant kelp LN with a viscosity of 20 mpas into a mixture of potassium chloride and magnesium chloride with a concentration of 8% for dissolution and classification, wherein the weight ratio of potassium salt to magnesium salt is 8.5:1.5, and the sodium alginate granules account for 12% of the mixed solution. After graded precipitation, the supernatant is taken by centrifugation, and then ethanol is used for precipitation to obtain high-purity GG segment sodium alginate, and the GG segment content accounts for 61%.
[0044] S2: dissolving the high-purity GG sodium alginate prepared in step S1 in deionized water to prepare a sol, and adding calcium carbonate in an amount of 0.2% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to prepare a sol solution; wherein the weight ratio of deionized water to high-purity GG sodium alginate added in the sol is deionized water: high-purity GG sodium alginate = 6:1.
[0045] S3 refines the sol solution prepared in S2 at 65° C. for 45 minutes and then performs vacuum degassing.
[0046] S4: adding glucurone to the S3 glue solution, the amount of which is 0.3% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0047] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.4%. Then, high-purity GG sodium alginate plant-based enteric capsules are obtained after drying.
[0048] Example 3
[0049] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method of the present invention comprises the following steps:
[0050] S1 adds medical grade sodium alginate granules extracted from giant kelp LF with a viscosity of 10 mpas to a mixture of potassium chloride and magnesium chloride at a concentration of 15% for dissolution and classification, wherein the weight ratio of potassium salt to magnesium salt is 9:1, and the sodium alginate granules account for 10% of the mixed solution. After graded precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain high-purity GG segment sodium alginate, with the GG segment content accounting for 85%.
[0051] S2: dissolving the high-purity GG sodium alginate prepared in step S1 in deionized water to prepare a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to prepare a sol solution; wherein the weight ratio of deionized water to high-purity GG sodium alginate added in the sol is deionized water: high-purity GG sodium alginate = 7:1.
[0052] S3 refines the sol solution prepared in S2 at 50° C. for 40 minutes and then performs vacuum degassing.
[0053] S4: adding glucurone to the S3 glue solution, the amount of which is 0.2% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0054] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.3%, and then dried to obtain high-purity GG sodium alginate plant-based enteric capsules.
[0055] Example 4
[0056] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method of the present invention comprises the following steps:
[0057] S1 adds medical grade sodium alginate granules extracted from kelp with a viscosity of 70 mpas to a 20% potassium chloride and magnesium chloride mixture for dissolution and grading, wherein the weight ratio of potassium salt to magnesium salt is 9:1, and the sodium alginate granules account for 6% of the mixed solution. After graded precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain high-purity GG segment sodium alginate, with the GG segment content accounting for 50%.
[0058] S2: dissolving the high-purity GG sodium alginate prepared in step S1 in deionized water to prepare a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to prepare a sol solution; wherein the weight ratio of deionized water to high-purity GG sodium alginate added in the sol is deionized water: high-purity GG sodium alginate = 8:1.
[0059] S3 refines the sol solution prepared in S2 at 55° C. for 30 minutes and then performs vacuum degassing.
[0060] S4: adding glucurone to the S3 glue solution, the amount of which is 0.3% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0061] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.3%, and then dried to obtain high-purity GG sodium alginate plant-based enteric capsules.
[0062] Example 5
[0063] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method of the present invention comprises the following steps:
[0064] S1 adds medical grade sodium alginate granules extracted from giant kelp LF with a viscosity of 70 mpas to a mixture of potassium chloride and magnesium chloride with a concentration of 30% for dissolution and classification, wherein the weight ratio of potassium salt to magnesium salt is 1:1, and the sodium alginate granules account for 6% of the mixed solution. After graded precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain high-purity GG segment sodium alginate, with the GG segment content accounting for 75%.
[0065] S2: dissolving the high-purity GG sodium alginate prepared in step S1 in deionized water to prepare a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to prepare a sol solution; wherein the weight ratio of deionized water to high-purity GG sodium alginate added in the sol is deionized water: high-purity GG sodium alginate = 10:1.
[0066] S3 refines the sol solution prepared in S2 at 40° C. for 50 minutes and then performs vacuum degassing.
[0067] S4: adding glucurone to the S3 glue solution, the amount of which is 0.3% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0068] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.1%, and then dried to obtain high-purity GG sodium alginate plant-based enteric capsules.
[0069] Comparative Example 1
[0070] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method comprises the following steps:
[0071] S1 adds medical grade sodium alginate granules extracted from giant kelp LN, with a viscosity of 50mpas and a solubility of 7%, to potassium chloride at a concentration of 15% for dissolution and classification. After classification and precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain sodium alginate, with a GG segment content of 89%.
[0072] S2: dissolving the sodium alginate obtained in step S1 in deionized water to obtain a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to obtain a sol solution; wherein the weight ratio of deionized water and sodium alginate added in the sol is deionized water: sodium alginate = 7:1.
[0073] S3 refines the sol solution prepared in S2 at 50° C. for 40 minutes and then performs vacuum degassing.
[0074] S4: adding glucurone to the S3 glue solution, the amount of which is 0.2% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0075] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.3%, and then dried to obtain the sodium alginate plant-based enteric capsules.
[0076] Comparative Example 2
[0077] The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method comprises the following steps:
[0078] S1 adds pharmaceutical grade sodium alginate granules extracted from giant kelp LN, with a viscosity of 50mpas and a solubility of 7%, to magnesium chloride at a concentration of 15% for dissolution and classification. After classification and precipitation, the supernatant is taken by centrifugation and then precipitated with ethanol to obtain sodium alginate, with a GG segment content of 9%.
[0079] S2: dissolving the GG segment sodium alginate obtained in step S1 in deionized water to obtain a sol, and adding calcium carbonate in an amount of 0.1% by weight of the sol; adding glycerol in an amount of 1% by weight of the sol; performing vacuum chopping and sol treatment to obtain a sol solution; wherein the weight ratio of deionized water to GG sodium alginate added in the sol is deionized water:GG sodium alginate=7:1.
[0080] S3 refines the sol solution prepared in S2 at 50° C. for 40 minutes and then performs vacuum degassing.
[0081] S4: adding glucurone to the S3 glue solution, the amount of which is 0.2% of the weight of the sol; applying a layer of glycerol inside the mold, and then performing a film pressing process.
[0082] After S5 film pressing, calcium water is sprayed in the film pressing mold, and the concentration of calcium water is 0.3%, and then dried to obtain the sodium alginate plant-based enteric capsules.
[0083] The performance test results of the sodium alginate plant-based enteric gel prepared above are as follows:
[0084]
[0085] The high-purity GG sodium alginate plant-based enteric capsules prepared by graded preparation in Example 1 to Example 5 of the preparation method of the present invention have a dense structure, good acid resistance and stability, and high mechanical strength, and therefore have an excellent sustained-release effect.
[0086] The basic reaction parameters of Comparative Example 1 and Comparative Example 2 are the same as those of Example 1, except that, in the process of graded precipitation, Comparative Example 1 only adopts dissolution and graded treatment in potassium chloride with a concentration of 15%, and in the process of graded precipitation, Comparative Example 2 only adopts dissolution and graded treatment in magnesium chloride with a concentration of 15%. Although Comparative Example 1 has good strength and acid stability, the sustained release time is too long; and the performance of the capsule finally obtained in Comparative Example 2 is poor in acid resistance stability, low in mechanical strength, and poor in sustained release effect compared with the performance of the sodium alginate plant-based enteric capsule obtained in Example 1. It can be clearly seen from the above table that the potassium salt and magnesium salt with a special concentration ratio are synergistically enhanced, the potassium salt dissolves the GG segment, and other segments are precipitated, while the magnesium salt precipitates the GG segment and other segments are dissolved, so by controlling the proportion of potassium salt and magnesium salt in the potassium salt and magnesium salt mixed solution, a high-purity GG segment sodium alginate is obtained. At the same time, the high-purity GG sodium alginate plant-based enteric capsules prepared by the present invention are based on high-purity GG segment sodium alginate and utilize a method of synergistically enhancing mechanical strength with microgels. The prepared sodium alginate plant-based enteric capsules have a dense structure, good acid resistance and stability, high mechanical strength, and excellent sustained-release effect, and can be widely used in the fields of biology and new medical technology.
[0087] The above are only embodiments of the present invention. For example, when the viscosity of sodium alginate is less than or equal to 80 mpas and the dissolution concentration is 1%-15%, the graded preparation of high-purity GG sodium alginate plant-based enteric capsules and methods of the present invention can be achieved.
[0088] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
Claims
1. A method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method, characterized in that: The method comprises the following steps: adding sodium alginate granules to a potassium salt and magnesium salt mixed solution to dissolve, extracting high-purity GG chain segment sodium alginate by graded precipitation treatment; and preparing high-purity GG plant-based enteric capsules by using the high-purity GG chain segment sodium alginate; The concentration of the potassium salt and magnesium salt mixed solution is 3%-30%, and the ratio of potassium salt to magnesium salt is 9:1-5:5; the weight ratio of the sodium alginate granular gel to the potassium salt and magnesium salt mixed solution is 1%-15%.
2. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 1, characterized in that: The steps include: S1, adding sodium alginate to a mixed solution of potassium salt and magnesium salt to dissolve, extracting high-purity GG segment sodium alginate by graded treatment, taking the supernatant by centrifugation, and then drying by alcohol precipitation to obtain high-purity GG sodium alginate; S2, adding the high-purity GG sodium alginate prepared in step S1 into deionized water, and adding calcium salt and glycerol, and mixing under vacuum to form a sol, and then performing a rubber refining process, and vacuum degassing; S3, adding lactone to adjust the pH and form microgel particles; S4, subjecting the microgel particles formed in step S3 to a film forming process; S5. Finally, the mold is sprayed with calcium water and dried to obtain high-purity GG plant-based enteric capsules.
3. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 2, characterized in that: In step S1, the sodium alginate is derived from one or more of kelp, giant kelp, ascophyllum, sargassum, and bark algae; The sodium alginate is a medical grade sodium alginate finished product granular glue, the viscosity of the sodium alginate is less than or equal to 80 mpas, and the dissolution concentration is 1%-15%.
4. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 2, characterized in that: Step S1, in the potassium salt and magnesium salt mixed solution, the potassium salt is one or both of potassium citrate and potassium chloride; the magnesium salt is one or both of magnesium chloride and magnesium citrate.
5. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 1, characterized in that: Step S2, the weight ratio of deionized water and high-purity GG sodium alginate added to the sol is: deionized water: high-purity GG sodium alginate = 5-10:1; The calcium salt is calcium carbonate, and its dosage is 0.1%-0.3% of the weight of the sol; the glycerol dosage is 1%-3% of the weight of the sol.
6. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 1, characterized in that: In step S2, the specific conditions of the rubber mixing treatment are: a temperature of 40°C-80°C, a heat preservation reaction time of 30min-60min, and a vacuum degassing.
7. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 1, characterized in that: In step S3, the lactone is glucuronic acid lactone, the pH is adjusted to 4-6, and the amount thereof is 0.1%-0.5% of the weight of the sol.
8. The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to claim 2, characterized in that: In step S4, before the film forming, a layer of glycerin needs to be coated in the corresponding film forming mold; in step S5, the concentration of calcium water used in the calcium water spraying operation is 0.1%-1%.
9. A method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded preparation, characterized in that: The method for preparing high-purity GG sodium alginate plant-based enteric capsules by graded method according to any one of claims 1 to 8.