Astaxanthin soft capsule composition for assisting in lowering blood pressure and preparation process of astaxanthin soft capsule composition

By modifying the use of zein-modified lactoferrin and ternary complexes, astaxanthin soft capsules were prepared, which solved the problem of excessively rapid astaxanthin release in the prior art, and achieved the long-term sustained release of astaxanthin and the continuous effect of assisting blood pressure lowering.

CN119950455AInactive Publication Date: 2025-05-09SHANDONG DONGKAI PHARMACEUTICAL CO LTD
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Patent Information

Application Number
CN202510193568.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-02-21
Publication Date
2025-05-09
Estimated Expiration
Not applicable · inactive patent

AI Technical Summary

Technical Problem

Existing astaxanthin soft capsules are released too quickly in the gastric environment, and cannot effectively regulate the release time and rate of astaxanthin, resulting in insufficient assistance in reducing blood pressure.

Method used

Complex lactoferrin is prepared by zein modified lactoferrin, and is compounded with high methoxy pectin and p-coumarylquininic acid to form a ternary complex loaded astaxanthin, combined with gelatin and Arabic semi-lactose to make gelatin, and astaxanthin soft capsules are prepared by capsule pressing machine.

Benefits of technology

The use of zein-modified lactoferrin and ternary complexes has been extended, and the release time of astaxanthin is achieved, and the long-term sustained release of astaxanthin on vascular smooth muscle cells is improved, which has improved the duration and accuracy of its auxiliary blood pressure reduction.

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Abstract

The invention relates to the technical field of soft capsule preparations, in particular to an astaxanthin soft capsule composition for assisting in lowering blood pressure and a preparation process thereof. The preparation process comprises the following steps: preparing composite lactoferrin powder; preparing a ternary complex; preparing astaxanthin powder; and preparing the astaxanthin soft capsule composition for assisting in lowering blood pressure. According to the invention, zein is used for modifying lactoferrin to prepare composite lactoferrin powder, zein and lactoferrin are compounded, and zein is modified on lactoferrin through a co-assembly mode of protein / protein under non-covalent action, so that the water solubility of zein is improved, and in addition, the water solubility of zein is improved. Through modification of zein, the astaxanthin can be slowly released by the compound protein, and the action time of the astaxanthin is prolonged, so that the lasting time of the antihypertensive action of the astaxanthin soft capsule composition is prolonged.
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Description

Technical Field

[0001] The invention relates to the technical field of soft capsule preparations, and in particular to an astaxanthin soft capsule composition for assisting in lowering blood pressure and a preparation process thereof. Background Art

[0002] Astaxanthin is a powerful carotenoid antioxidant that is widely found in certain algae, yeast, salmon, shrimp and other organisms. In recent years, more and more studies have shown that astaxanthin not only has significant antioxidant, anti-inflammatory and anti-aging effects, but also can reduce the blood pressure of hypertensive rats by inhibiting the proliferation of vascular smooth muscle cells and restoring mitochondrial function, and alleviate vascular remodeling, which has the function of assisting in lowering blood pressure.

[0003] Astaxanthin is generally encapsulated in soft capsules for oral administration. The capsule shell of the soft capsule is generally made of gelatin. Gelatin has good moldability and elasticity, good biocompatibility, fast decomposition speed in the gastric environment, and can be quickly administered. However, simply using gelatin as the capsule shell cannot regulate the release time and rate of the contents. The auxiliary effect of astaxanthin on lowering blood pressure requires long-term slow release to affect the proliferation of vascular smooth muscle cells. Therefore, directly releasing a large amount of astaxanthin cannot achieve the effect of assisting in lowering blood pressure, but requires long-term slow release of astaxanthin to achieve the effect of assisting in lowering blood pressure. Therefore, the present invention provides an astaxanthin soft capsule composition for assisting in lowering blood pressure and a preparation process thereof to solve the above problems. Summary of the invention

[0004] In view of the deficiencies in the prior art, the object of the present invention is to provide an astaxanthin soft capsule composition for assisting in lowering blood pressure and a preparation process thereof.

[0005] A preparation process of an astaxanthin soft capsule composition for assisting in lowering blood pressure comprises the following steps: S1: Preparation of composite lactoferrin powder The lactoferrin and zein are mixed to prepare a composite protein solution, and the composite protein solution is subjected to ultrasonic treatment, freeze-dried, crushed and sieved to obtain composite lactoferrin powder; S2: Preparation of ternary complexes The composite lactoferrin powder is dissolved in ultrapure water to obtain a composite lactoferrin solution, and then a high methoxy pectin solution is added to obtain a protein-high methoxy pectin complex, and p-coumarylquinic acid is added to the protein-high methoxy pectin complex to obtain a ternary complex; S3: Preparation of astaxanthin powder Adding Haematococcus pluvialis powder to deionized water, heating it, adding hydrochloric acid solution, stirring and filtering to remove the filtrate, adding the filter residue to deionized water of equal volume to the hydrochloric acid solution to obtain a treated liquid, homogenizing the treated liquid, spray drying to obtain treated algae powder, adding the treated algae powder to ethyl acetate for extraction, rotary evaporation, and drying with nitrogen to obtain astaxanthin powder; S4: Preparation of astaxanthin soft capsule composition for assisting in lowering blood pressure Astaxanthin powder is added into anhydrous ethanol to obtain an astaxanthin ethanol solution, and then the astaxanthin ethanol solution is added into the ternary complex, and dried with nitrogen to obtain protein-loaded astaxanthin nanopowder, and arabinolactose is mixed with deionized water to obtain an arabinolactose solution, gelatin is soaked in water, and the arabinolactose solution is added to obtain a rubber material, and the rubber material is added into a capsule machine, and then the protein-loaded astaxanthin nanopowder is added, and the capsule machine is started for pilling to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0006] Furthermore, step S1 prepares the composite lactoferrin powder, comprising the following steps: S1.1: adding 5-6 parts by weight of lactoferrin to 95-100 parts by weight of deionized water, and stirring at a speed of 600-650 r / min for 1-1.5 hours, then adjusting the pH value to 12-12.5 with a NaOH solution, and then adding 2-3 parts by weight of zein, and adjusting the total protein concentration to 10-20 mg / mL, to obtain a composite protein solution; S1.2: The composite protein solution is ultrasonically treated for 5-10 minutes, and then stirred at a speed of 500-550r / min for 1-2 hours, and then the pH value is adjusted to 7-7.5 with HCl solution, and then centrifuged for 10-15 minutes, the supernatant is taken, the supernatant is freeze-dried, and crushed through an 80-mesh sieve to obtain composite lactoferrin powder.

[0007] Furthermore, step S2 prepares the ternary complex, comprising the following steps: S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2-2.5h, adjusting the concentration of the composite lactoferrin powder to 2-3mg / mL to obtain a composite lactoferrin solution, adding 2-3mg / mL of a high methoxy pectin solution, and adjusting the pH value to 7-8 to obtain a protein-high methoxy pectin complex; S2.2: Add p-coumaroylquinic acid to the protein-high methoxy pectin complex, the mass proportion of p-coumaroylquinic acid is 0.02-0.08%, and adjust the pH value to 5-7, then stir at a speed of 200-300 r / min for 2-2.5h to obtain a ternary complex.

[0008] Further, step S3 of preparing astaxanthin powder comprises the following steps: S3.1: Add the Haematococcus pluvialis powder into deionized water, heat to 70-75°C, add 4-5 times the volume of hydrochloric acid solution, stir at 600-800r / min for 2-5min, then filter to remove the filtrate, add deionized water of the same volume as the hydrochloric acid solution to the residue, and obtain a treated solution; S3.2: homogenizing the treated liquid at 60 MPa for 3 times, and then spray drying at high temperature for 20-35 min at a temperature of 185-190° C. to obtain treated algae powder; S3.3: The treated algae powder is added to ethyl acetate for extraction at a solid-liquid ratio of 1 g: (8-12) mL, followed by centrifugation at 2000-2100 r / min for 10-15 min, and then rotary evaporated to one third of the original volume at -0.06 MPa and 45-50°C, and blown dry with nitrogen to obtain astaxanthin powder.

[0009] Furthermore, step S4 prepares an astaxanthin soft capsule composition for assisting in lowering blood pressure, comprising the following steps: S4.1: Add astaxanthin powder to anhydrous ethanol and adjust the astaxanthin content to 1-2 mg / mL to obtain an astaxanthin ethanol solution, then add the astaxanthin ethanol solution to the ternary complex, the volume ratio of the astaxanthin ethanol solution to the ternary complex is 1:(20-25), and adjust the pH value to 6-7, react in the dark for 30-35 minutes, blow dry with nitrogen, and obtain protein-loaded astaxanthin nanopowder; S4.2: Mix arabinol and deionized water at a solid-liquid ratio of 1 g: (12-15) mL to obtain an arabinol solution, soak gelatin in water for 20-25 minutes, adjust the pH to 4-5, then heat to 50-60°C, add the arabinol solution, and control the concentration of arabinol to 0.2-0.8%, stir for 10-15 minutes, and obtain a rubber compound; S4.3: Add the rubber material into the capsule machine, then add the protein-loaded astaxanthin nanopowder, start the capsule machine for pill pressing, set the drug loading of the soft capsule to 0.5-0.6 g / capsule, set at 25-30℃ for 2-2.5h, and dry at 30-40℃ for 24-26h to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0010] Furthermore, the freeze-drying temperature is minus 20-40°C and the time is 24-26 hours.

[0011] Furthermore, the volume ratio of the composite lactoferrin solution to the high methoxyl pectin solution is (2-3):1.

[0012] Furthermore, the extraction temperature is 40-60°C and the extraction time is 90-100 min.

[0013] Furthermore, the liquid ratio of gelatin to water is 1 g: (10-12) mL.

[0014] An astaxanthin soft capsule composition for assisting in lowering blood pressure is prepared by the preparation process of the above-mentioned astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0015] Compared with the prior art, the present invention has at least the following beneficial effects: 1. The present invention prepares composite lactoferrin powder by modifying lactoferrin with zein. Zein is a protein with good biocompatibility and stability and good encapsulation ability. However, zein contains a high proportion of hydrophobic amino acids, so it shows strong hydrophobicity, resulting in poor solubility in water. Therefore, simply using zein to load astaxanthin easily leads to uneven dispersion of the product in the gel emulsion. Therefore, zein is compounded with lactoferrin, and through the co-assembly mode of protein / protein under non-covalent action, zein is modified on lactoferrin, thereby improving the water solubility of zein, and after modification of zein, the composite protein can release astaxanthin slowly, prolong the action time of astaxanthin, thereby prolonging the duration of the blood pressure lowering effect of astaxanthin soft capsule.

[0016] 2. The present invention prepares a ternary complex by compounding composite lactoferrin, high methoxy pectin and p-coumarylquinic acid. The ternary complex is used to load astaxanthin. The three can form a proteoglycan-phenolic acid ternary system to stabilize the colloid. In addition, p-coumarylquinic acid has antioxidant properties. By using p-coumarylquinic acid as the added phenolic acid, p-coumarylquinic acid can be combined with high methoxy pectin, thereby improving the activity of high methoxy pectin, preventing high methoxy pectin from losing oxygen groups over time, thereby causing its activity to weaken, and regulating the release rate of astaxanthin to be smooth and stable, thereby improving the accuracy of astaxanthin's auxiliary hypotensive effect. High methoxy pectin is mainly used as a viscosity material in the ternary complex to polymerize the three together, and has a certain film-forming property. After loading astaxanthin, astaxanthin can be packaged to reduce the release rate of astaxanthin, thereby controlling the release time of astaxanthin to a certain extent and improving the stability of astaxanthin.

[0017] 3. The present invention mixes gelatin and arabinoglycolic acid to form a glue for wrapping protein-loaded astaxanthin nanopowder. The positively charged gelatin and the negatively charged arabinoglycolic acid can form a soluble complex through electrostatic attraction. Compared with a discrete system formed by non-electrostatic attraction, the glue formed by electrostatic attraction has better gel properties and a denser gel structure. The dense gel structure is easier to self-assemble and wrap protein powder. Therefore, gelatin and arabinoglycolic acid can well load protein-loaded astaxanthin nanopowder and are easier to form soft capsules. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings, which are incorporated herein and constitute a part of the specification, illustrate embodiments of the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable those skilled in the relevant art to make and use the present disclosure.

[0019] Figure 1 The present invention is a flow chart of the preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure used in the embodiments of the present invention.

[0020] Figure 2 It is a line graph of the astaxanthin release rate of in vitro simulated digestion of Examples 1-3 of the present invention and Comparative Example 1. DETAILED DESCRIPTION

[0021] The following is a detailed description of an astaxanthin soft capsule composition for assisting in lowering blood pressure and its preparation process provided by the present invention in conjunction with the accompanying drawings and specific embodiments. At the same time, it is explained here that in order to make the embodiments more detailed, the following embodiments are the best and preferred embodiments, and those skilled in the art may also adopt other alternatives to implement some known technologies; and the accompanying drawings are only for a more specific description of the embodiments, and are not intended to specifically limit the present invention.

[0022] Example 1: A preparation process of an astaxanthin soft capsule composition for assisting in lowering blood pressure, such as Figure 1 As shown, the following steps are included: S1: Preparation of composite lactoferrin powder S1.1: 5 parts by mass of lactoferrin was added to 95 parts by mass of deionized water, and stirred at a speed of 600 r / min for 1 hour, and then the pH value was adjusted to 12 with a NaOH solution, and then 2 parts by mass of zein was added, and the total protein concentration was adjusted to 10 mg / mL to obtain a composite protein solution; S1.2: The composite protein solution was ultrasonically treated for 5 minutes, and then stirred at a speed of 500 r / min for 1 hour, and then the pH value was adjusted to 7 with HCl solution, and then centrifuged for 10 minutes, and the supernatant was taken and freeze-dried at a temperature of minus 20°C for 24 hours. The supernatant was crushed through an 80-mesh sieve to obtain composite lactoferrin powder.

[0023] S2: Preparation of ternary complexes S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2 h, adjusting the concentration of the composite lactoferrin powder to 2 mg / mL to obtain a composite lactoferrin solution, adding 2 mg / mL of high methoxy pectin solution, the volume ratio of the composite lactoferrin solution to the high methoxy pectin solution is 2:1, and adjusting the pH value to 7 to obtain a protein-high methoxy pectin complex; S2.2: Add p-coumaroylquinic acid to the protein-high methoxy pectin complex, the mass proportion of p-coumaroylquinic acid is 0.02%, and the pH value is adjusted to 5, followed by stirring at a speed of 200 r / min for 2 hours to obtain a ternary complex.

[0024] S3: Preparation of astaxanthin powder S3.1: Add the Haematococcus pluvialis powder into deionized water, heat to 70°C, add 4 times the volume of hydrochloric acid solution, stir at 600r / min for 2min, then filter to remove the filtrate, add deionized water of the same volume as the hydrochloric acid solution to the residue, and obtain a treated solution; S3.2: homogenizing the treated liquid at 60 MPa for 3 times, and then spray drying at high temperature for 20 min at a temperature of 185°C to obtain treated algae powder; S3.3: The treated algae powder was added to ethyl acetate at a solid-liquid ratio of 1g:8mL for extraction at an extraction temperature of 40°C for 90min, followed by centrifugation at 2000r / min for 10min, and then rotary evaporated at -0.06MPa and 45°C to one third of the original volume, and blown dry with nitrogen to obtain astaxanthin powder.

[0025] S4: Preparation of astaxanthin soft capsule composition for assisting in lowering blood pressure S4.1: Add astaxanthin powder to anhydrous ethanol and adjust the astaxanthin content to 1 mg / mL to obtain an astaxanthin ethanol solution, then add the astaxanthin ethanol solution to the ternary complex, the volume ratio of the astaxanthin ethanol solution to the ternary complex is 1:20, and the pH value is adjusted to 6, react in the dark for 30 minutes, blow dry with nitrogen to obtain protein-loaded astaxanthin nanopowder; S4.2: Arabinol and deionized water are mixed at a solid-liquid ratio of 1 g:12 mL to obtain an arabinol solution, gelatin is soaked in water for 20 minutes, the solid-liquid ratio of gelatin to water is 1 g:10 mL, the pH is adjusted to 4, and then heated to 50°C, the arabinol solution is added, and the concentration of arabinol is controlled to be 0.2%, and stirred for 10 minutes to obtain a rubber compound; S4.3: Add the rubber material into the capsule machine, then add the protein-loaded astaxanthin nanopowder, start the capsule machine for pill pressing, set the drug loading of the soft capsule to 0.5 g / pill, fix at 25°C for 2h, and dry at 30°C for 24h to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0026] Example 2: A preparation process of an astaxanthin soft capsule composition for assisting in lowering blood pressure, such as Figure 1 As shown, the following steps are included: S1: Preparation of composite lactoferrin powder S1.1: 6 parts by mass of lactoferrin were added to 100 parts by mass of deionized water, and stirred at a speed of 600 r / min for 1 hour, and then the pH value was adjusted to 12 with a NaOH solution, and then 3 parts by mass of zein were added, and the total protein concentration was adjusted to 10 mg / mL to obtain a composite protein solution; S1.2: The composite protein solution was ultrasonically treated for 5 minutes, and then stirred at a speed of 500 r / min for 1 hour, and then the pH value was adjusted to 7 with HCl solution, and then centrifuged for 10 minutes, and the supernatant was taken and freeze-dried at a temperature of minus 20°C for 24 hours. The supernatant was crushed through an 80-mesh sieve to obtain composite lactoferrin powder.

[0027] S2: Preparation of ternary complexes S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2 h, adjusting the concentration of the composite lactoferrin powder to 3 mg / mL to obtain a composite lactoferrin solution, adding 3 mg / mL of high methoxy pectin solution, the volume ratio of the composite lactoferrin solution to the high methoxy pectin solution is 3:1, and adjusting the pH value to 7 to obtain a protein-high methoxy pectin complex; S2.2: Add p-coumaroylquinic acid to the protein-high methoxy pectin complex, with the mass proportion of p-coumaroylquinic acid being 0.08%, and adjust the pH value to 5, followed by stirring at a speed of 200 r / min for 2 h to obtain a ternary complex.

[0028] S3: Preparation of astaxanthin powder S3.1: Add the Haematococcus pluvialis powder into deionized water, heat to 70°C, add 4 times the volume of hydrochloric acid solution, stir at 600r / min for 2min, then filter to remove the filtrate, add deionized water of the same volume as the hydrochloric acid solution to the residue, and obtain a treated solution; S3.2: homogenizing the treated liquid at 60 MPa for 3 times, and then spray drying at high temperature for 20 min at a temperature of 185°C to obtain treated algae powder; S3.3: The treated algae powder was added to ethyl acetate at a solid-liquid ratio of 1g:12mL for extraction at 40°C for 90min, followed by centrifugation at 2000r / min for 10min, and then rotary evaporated at -0.06MPa and 45°C to one third of the original volume, and blown dry with nitrogen to obtain astaxanthin powder.

[0029] S4: Preparation of astaxanthin soft capsule composition for assisting in lowering blood pressure S4.1: Add astaxanthin powder to anhydrous ethanol and adjust the astaxanthin content to 1 mg / mL to obtain an astaxanthin ethanol solution, then add the astaxanthin ethanol solution to the ternary complex, the volume ratio of the astaxanthin ethanol solution to the ternary complex is 1:25, and the pH value is adjusted to 6, react in the dark for 30 minutes, blow dry with nitrogen to obtain protein-loaded astaxanthin nanopowder; S4.2: Arabinol and deionized water are mixed at a solid-liquid ratio of 1 g:15 mL to obtain an arabinol solution, gelatin is soaked in water for 20 minutes, the solid-liquid ratio of gelatin to water is 1 g:10 mL, the pH is adjusted to 4, and then heated to 50°C, the arabinol solution is added, and the concentration of arabinol is controlled to be 0.2%, and stirred for 10 minutes to obtain a rubber compound; S4.3: Add the rubber material into the capsule machine, then add the protein-loaded astaxanthin nanopowder, start the capsule machine for pill pressing, set the drug loading of the soft capsule to 0.6 g / pill, fix at 25°C for 2h, and dry at 30°C for 24h to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0030] Example 3: A preparation process of an astaxanthin soft capsule composition for assisting in lowering blood pressure, such as Figure 1 As shown, the following steps are included: S1: Preparation of composite lactoferrin powder S1.1: 5 parts by mass of lactoferrin was added to 95 parts by mass of deionized water, and stirred at a speed of 600 r / min for 1.5 h, and then the pH value was adjusted to 12.5 with a NaOH solution, and then 2 parts by mass of zein was added, and the total protein concentration was adjusted to 10 mg / mL to obtain a composite protein solution; S1.2: The composite protein solution was ultrasonically treated for 10 minutes, and then stirred at a speed of 550r / min for 2 hours, and then the pH value was adjusted to 7.5 with HCl solution, and then centrifuged for 15 minutes, and the supernatant was taken and freeze-dried at a temperature of minus 40°C for 26 hours. The supernatant was crushed through an 80-mesh sieve to obtain composite lactoferrin powder.

[0031] S2: Preparation of ternary complexes S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2.5 h, adjusting the concentration of the composite lactoferrin powder to 2 mg / mL to obtain a composite lactoferrin solution, adding 2 mg / mL of high methoxy pectin solution, the volume ratio of the composite lactoferrin solution to the high methoxy pectin solution is 2:1, and adjusting the pH value to 8 to obtain a protein-high methoxy pectin complex; S2.2: Add p-coumaroylquinic acid to the protein-high methoxy pectin complex, with the mass proportion of p-coumaroylquinic acid being 0.02%, and adjust the pH value to 7, followed by stirring at a speed of 300 r / min for 2.5 h to obtain a ternary complex.

[0032] S3: Preparation of astaxanthin powder S3.1: Add the Haematococcus pluvialis powder into deionized water, heat to 75°C, add 4 times the volume of hydrochloric acid solution, stir at 800r / min for 5min, then filter to remove the filtrate, add deionized water of the same volume as the hydrochloric acid solution to the residue, and obtain a treated solution; S3.2: homogenizing the treated liquid at 60 MPa for 3 times, and then spray drying at high temperature for 35 min at a temperature of 185°C to obtain treated algae powder; S3.3: The treated algae powder was added to ethyl acetate at a solid-liquid ratio of 1g:8mL for extraction at an extraction temperature of 60°C for 100min, followed by centrifugation at 2100r / min for 15min, and then rotary evaporated at -0.06MPa and 50°C to one third of the original volume, and blown dry with nitrogen to obtain astaxanthin powder.

[0033] S4: Preparation of astaxanthin soft capsule composition for assisting in lowering blood pressure S4.1: Add astaxanthin powder to anhydrous ethanol and adjust the astaxanthin content to 1 mg / mL to obtain an astaxanthin ethanol solution, then add the astaxanthin ethanol solution to the ternary complex, the volume ratio of the astaxanthin ethanol solution to the ternary complex is 1:20, and adjust the pH value to 4, react in the dark for 40 minutes, blow dry with nitrogen to obtain protein-loaded astaxanthin nanopowder; S4.2: Arabinol and deionized water are mixed at a solid-liquid ratio of 1 g:12 mL to obtain an arabinol solution, gelatin is soaked in water for 25 minutes, the solid-liquid ratio of gelatin to water is 1 g:10 mL, the pH is adjusted to 5, and then heated to 60°C, the arabinol solution is added, and the concentration of arabinol is controlled to be 0.2%, and stirred for 15 minutes to obtain a rubber compound; S4.3: Add the rubber material into the capsule machine, then add the protein-loaded astaxanthin nanopowder, start the capsule machine for pill pressing, set the drug loading of the soft capsule to 0.5 g / pill, fix at 30°C for 2.5 hours, and dry at 40°C for 26 hours to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

[0034] Comparative Example 1: Comparative Example 1 is an astaxanthin soft capsule composition on the market.

[0035] Comparative Example 2: Compared with Example 1, the difference of Comparative Example 2 is that step S1 is not performed, and the composite lactoferrin powder is replaced with lactoferrin powder in step S2.1, specifically: "S2.1: dissolve the lactoferrin powder in ultrapure water and stir for 2 hours, adjust the concentration of the lactoferrin powder to 2 mg / mL to obtain a lactoferrin solution, and then add 2 mg / mL of high methoxy pectin solution, the volume ratio of the lactoferrin solution to the high methoxy pectin solution is 2:1, and the pH value is adjusted to 7 to obtain a protein-high methoxy pectin complex", and the other steps remain unchanged. The prepared astaxanthin soft capsule composition for assisting in lowering blood pressure is recorded as Comparative Example 2.

[0036] Comparative Example 3: Compared with Example 1, the difference of Comparative Example 3 is that the high methoxy pectin solution is not added in step S2.1, specifically: "S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2h, adjusting the concentration of the composite lactoferrin powder to 2mg / mL, and obtaining a composite lactoferrin solution; S2.2: adding p-coumaroylquinic acid to the composite lactoferrin solution, wherein the mass proportion of p-coumaroylquinic acid is 0.02%, and adjusting the pH value to 5, followed by stirring at a speed of 200 r / min for 2 h to obtain a "binary complex". The binary complex is used to replace the ternary complex in step S4, and the other steps remain unchanged. The prepared astaxanthin soft capsule composition for assisting in lowering blood pressure is recorded as Comparative Example 3.

[0037] Comparative Example 4: Compared with Example 1, the difference of Comparative Example 4 is that p-coumarylquinic acid is not added in step S2.2, specifically: "S2.1: dissolve the composite lactoferrin powder in ultrapure water and stir for 2h, adjust the concentration of the composite lactoferrin powder to 2mg / mL, and obtain a composite lactoferrin solution, and then add 2mg / mL of high methoxy pectin solution, the volume ratio of the composite lactoferrin solution to the high methoxy pectin solution is 2:1, and the pH value is adjusted to 7 to obtain a binary complex", and the binary complex is used instead of the ternary complex in step S4, and the other steps remain unchanged. The prepared astaxanthin soft capsule composition for assisting in lowering blood pressure is recorded as Comparative Example 4.

[0038] Comparative Example 5: Compared with Example 1, the difference of Comparative Example 5 is that p-coumaroylquinic acid is not added in step S2.2, but 5-caffeoylquinic acid is added, specifically: "S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2 hours, adjusting the concentration of the composite lactoferrin powder to 2 mg / mL to obtain a composite lactoferrin solution, and then adding 2 mg / mL of high methoxy pectin solution, the volume ratio of the composite lactoferrin solution to the high methoxy pectin solution is 2:1, and the pH value is adjusted to 7 to obtain a protein-high methoxy pectin complex; S2.2: Add 5-caffeoylquinic acid to the protein-high methoxy pectin complex, the mass proportion of 5-caffeoylquinic acid is 0.02%, and the pH value is adjusted to 5, followed by stirring at a speed of 200 r / min for 2 hours to obtain a ternary complex. The remaining steps remain unchanged, and the prepared astaxanthin soft capsule composition for assisting in lowering blood pressure is recorded as Comparative Example 5.

[0039] Two simulated gastric fluids were prepared. The simulated gastric fluid SGF contained 3.2 mg / mL pepsin and had a pH of 2; the simulated gastric fluid SIF contained 10 mg / mL trypsin and 5 mg / mL sodium deoxycholate and had a pH of 7. Examples 1-3 and Comparative Examples 1-5 were mixed with simulated gastric fluid SGF, respectively, and shaken at 100 r / min for 2 h in a 37°C air bath shaker. The pH of the mixture was then adjusted to 7, and simulated gastric fluid SIF was added. The mixture was allowed to react for 4 h, and samples were taken every 1 h to determine the astaxanthin content of the samples. The results of Examples 1-3 and Comparative Example 1 of the commercially available product are shown in Figure 1. Figure 2 The results of Example 1 and Comparative Examples 2-5 are shown in Table 1.

[0040] Table 1 Release rate 0h 1h 2h 3h 4h 5h 6h 7h Example 1 0 18 22 31 39 48 59 63 Comparative Example 2 0 26 47 61 75 89 98 100 Comparative Example 3 0 24 31 39 46 55 64 74 Comparative Example 4 0 22 33 42 48 56 65 76 Comparative Example 5 0 27 33 36 44 47 54 55 from Figure 2 It can be seen that the astaxanthin release rate of Comparative Example 1 is higher than that of the embodiment at the beginning, the release rate slowly decreases within 7 hours, and is close to the release rate of the embodiment at the 7th hour. It can be seen that compared with commercially available products, the present invention can reduce the release rate of astaxanthin at the 1st hour, and release astaxanthin at a relatively average release rate in the subsequent 7 hours, thereby ensuring that the release amount of astaxanthin in each time period is relatively equal, thereby ensuring that astaxanthin can play an auxiliary blood pressure lowering effect in each time period, while the release rate of Comparative Example 1 is higher at the 1st hour, and the subsequent release rate is not stable, which will result in the uneven release of astaxanthin, and with the passage of time, the release rate of astaxanthin decreases. It can be seen that the release amount of astaxanthin in Comparative Example 1 will decrease with the passage of time, so the auxiliary blood pressure lowering effect will also decrease.

[0041] As can be seen from Table 1, the release rate of Example 1 at 1 hour is 18%, while the release rate of Comparative Example 2 at 1 hour reaches 26%, and then the release rate gradually increases, reaching 98% at 6 hours, and the release rate of Example 1 at 7 hours is only 63%. It can be seen that without adding zein but only using lactoferrin, a single protein will quickly release astaxanthin, so that all astaxanthin is released in about 6 hours, and a better sustained-release effect cannot be achieved.

[0042] The release rates of Comparative Examples 3 and 4 at 1 hour were 24% and 22%, respectively, and the release rates at 7 hours were 74% and 76%, respectively, indicating that the encapsulation effect of the binary complex on astaxanthin is not as good as that of the ternary complex. Therefore, the astaxanthin soft capsule composition prepared by the binary complex has an astaxanthin release of more than 70% at 7 hours, while that of Example 1 is only 63%. The residual astaxanthin amount of Comparative Examples 3-4 at 7 hours is not as good as that of the example, which shows that the overall release time of astaxanthin will also be shorter. It can be inferred that the sustained-release effect of the example on astaxanthin is more obvious.

[0043] The release rate of Comparative Example 5 is 27% at 1 hour, while the release rate is only 55% at 7 hours, and the release rate is 54% at 6 hours. It can be seen that the release rate of Comparative Example 5 is greatly reduced after 6 hours, and almost no astaxanthin is released. This is because there is no combination of p-coumarylquinic acid and high methoxy pectin. High methoxy pectin loses oxygen groups over time and its activity weakens. After the film is formed and wrapped around astaxanthin, it loses its activity and no longer releases astaxanthin. Therefore, the release rate of astaxanthin is difficult to increase after 6 hours, and the remaining astaxanthin in the soft capsule is difficult to release, but will be excreted from the body with the action of the digestive system, and it is difficult to play a role in assisting in lowering blood pressure.

[0044] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A preparation process of an astaxanthin soft capsule composition for assisting in lowering blood pressure, characterized in that: The steps include: S1: Preparation of composite lactoferrin powder The lactoferrin and zein are mixed to prepare a composite protein solution, and the composite protein solution is subjected to ultrasonic treatment, freeze-dried, crushed and sieved to obtain composite lactoferrin powder; S2: Preparation of ternary complexes The composite lactoferrin powder is dissolved in ultrapure water to obtain a composite lactoferrin solution, and then a high methoxy pectin solution is added to obtain a protein-high methoxy pectin complex, and p-coumarylquinic acid is added to the protein-high methoxy pectin complex to obtain a ternary complex; S3: Preparation of astaxanthin powder Adding Haematococcus pluvialis powder to deionized water, heating it, adding hydrochloric acid solution, stirring and filtering to remove the filtrate, adding the filter residue to deionized water of equal volume to the hydrochloric acid solution to obtain a treated liquid, homogenizing the treated liquid, spray drying to obtain treated algae powder, adding the treated algae powder to ethyl acetate for extraction, rotary evaporation, and drying with nitrogen to obtain astaxanthin powder; S4: Preparation of astaxanthin soft capsule composition for assisting in lowering blood pressure Astaxanthin powder is added into anhydrous ethanol to obtain an astaxanthin ethanol solution, and then the astaxanthin ethanol solution is added into the ternary complex, and dried with nitrogen to obtain protein-loaded astaxanthin nanopowder, and arabinolactose is mixed with deionized water to obtain an arabinolactose solution, gelatin is soaked in water, and the arabinolactose solution is added to obtain a rubber material, and the rubber material is added into a capsule machine, and then the protein-loaded astaxanthin nanopowder is added, and the capsule machine is started for pilling to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

2. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 1, characterized in that: Step S1 prepares the composite lactoferrin powder, comprising the following steps: S1.1: adding 5-6 parts by weight of lactoferrin to 95-100 parts by weight of deionized water, and stirring at a speed of 600-650 r / min for 1-1.5 hours, then adjusting the pH value to 12-12.5 with a NaOH solution, and then adding 2-3 parts by weight of zein, and adjusting the total protein concentration to 10-20 mg / mL, to obtain a composite protein solution; S1.2: The composite protein solution is ultrasonically treated for 5-10 minutes, and then stirred at a speed of 500-550r / min for 1-2 hours, and then the pH value is adjusted to 7-7.5 with HCl solution, and then centrifuged for 10-15 minutes, the supernatant is taken, the supernatant is freeze-dried, and crushed through an 80-mesh sieve to obtain composite lactoferrin powder.

3. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 2, characterized in that: Step S2 prepares the ternary complex, comprising the following steps: S2.1: dissolving the composite lactoferrin powder in ultrapure water and stirring for 2-2.5h, adjusting the concentration of the composite lactoferrin powder to 2-3mg / mL to obtain a composite lactoferrin solution, adding 2-3mg / mL of a high methoxy pectin solution, and adjusting the pH value to 7-8 to obtain a protein-high methoxy pectin complex; S2.2: Add p-coumaroylquinic acid to the protein-high methoxy pectin complex, the mass proportion of p-coumaroylquinic acid is 0.02-0.08%, and adjust the pH value to 5-7, then stir at a speed of 200-300 r / min for 2-2.5h to obtain a ternary complex.

4. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 3, characterized in that: Step S3 prepares astaxanthin powder, comprising the following steps: S3.1: Add the Haematococcus pluvialis powder into deionized water, heat to 70-75°C, add 4-5 times the volume of hydrochloric acid solution, stir at 600-800r / min for 2-5min, then filter to remove the filtrate, add deionized water of the same volume as the hydrochloric acid solution to the residue, and obtain a treated solution; S3.2: homogenizing the treated liquid at 60 MPa for 3 times, and then spray drying at high temperature for 20-35 min at a temperature of 185-190° C. to obtain treated algae powder; S3.3: The treated algae powder is added to ethyl acetate for extraction at a solid-liquid ratio of 1 g: (8-12) mL, followed by centrifugation at 2000-2100 r / min for 10-15 min, and then rotary evaporated to one third of the original volume at -0.06 MPa and 45-50°C, and blown dry with nitrogen to obtain astaxanthin powder.

5. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 4, characterized in that: Step S4 is to prepare an astaxanthin soft capsule composition for assisting in lowering blood pressure, comprising the following steps: S4.1: Add astaxanthin powder to anhydrous ethanol and adjust the astaxanthin content to 1-2 mg / mL to obtain an astaxanthin ethanol solution, then add the astaxanthin ethanol solution to the ternary complex, the volume ratio of the astaxanthin ethanol solution to the ternary complex is 1:(20-25), and adjust the pH value to 6-7, react in the dark for 30-35 minutes, blow dry with nitrogen, and obtain protein-loaded astaxanthin nanopowder; S4.2: Mix arabinol and deionized water at a solid-liquid ratio of 1 g: (12-15) mL to obtain an arabinol solution, soak gelatin in water for 20-25 minutes, adjust the pH to 4-5, then heat to 50-60°C, add the arabinol solution, and control the concentration of arabinol to 0.2-0.8%, stir for 10-15 minutes, and obtain a rubber compound; S4.3: Add the rubber material into the capsule machine, then add the protein-loaded astaxanthin nanopowder, start the capsule machine for pill pressing, set the drug loading of the soft capsule to 0.5-0.6 g / capsule, set at 25-30℃ for 2-2.5h, and dry at 30-40℃ for 24-26h to obtain an astaxanthin soft capsule composition for assisting in lowering blood pressure.

6. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 2, characterized in that: The freeze-drying temperature is minus 20-40°C and the time is 24-26 hours.

7. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 3, characterized in that: The volume ratio of the composite lactoferrin solution to the high methoxyl pectin solution is (2-3):

1.

8. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 4, characterized in that: The extraction temperature is 40-60°C and the extraction time is 90-100 minutes.

9. The preparation process of the astaxanthin soft capsule composition for assisting in lowering blood pressure according to claim 5, characterized in that: The liquid ratio of gelatin to water is 1g: (10-12)mL.

10. An astaxanthin soft capsule composition for assisting in lowering blood pressure, characterized in that: The astaxanthin soft capsule composition is prepared by the preparation process of any one of claims 1 to 9 for assisting in lowering blood pressure.

Citation Information

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