Oral liquid for promoting digestion, relieving stasis and supplementing calcium, iron and zinc and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to oral liquid for promoting digestion, relieving indigestion and supplementing calcium, iron and zinc and a preparation method thereof. Comprising the following steps: extracting and purifying rorippa formosana polysaccharide; preparing an auxiliary digestion promoting agent; preparing an aromatic digestion promoting agent; and compounding the oral liquid. The preparation method comprises the following steps: extracting rorippa formosana crude polysaccharide from rorippa formosana through water extraction and alcohol precipitation, then carrying out chromatography on the rorippa formosana crude polysaccharide by using a DEAE cellulose DE-52 column to prepare rorippa formosana polysaccharide, acetylating the rorippa formosana polysaccharide, and compounding with a mixed concentrated solution obtained by water extraction and concentration of hawthorn, coix seed and Chinese yam to obtain the rorippa formosana polysaccharide compound. The prepared auxiliary digestion promoting agent is applied to the oral liquid, so that the effects of promoting digestion and relieving stasis can be enhanced, and the absorption and utilization of the body on effective components of food can be promoted, thereby effectively improving and treating the dyspepsia problem of the human body, improving the appetite of children, and avoiding the phenomena of malnutrition and immunity decline caused by dyspepsia and poor appetite.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to an oral liquid for digestion and accumulation and supplement of calcium, iron and zinc and a preparation method thereof. BACKGROUND

[0002] Children are in the key stage of growth and development, and have vigorous metabolism, but the digestive system function is relatively weak and not yet perfect. In daily life, improper diet, improper food selection or dysfunction of the spleen and stomach can easily cause indigestion, poor appetite and other problems. If these problems cannot be effectively improved for a long period of time, not only will the absorption and utilization rate of the nutrients intake decrease, causing deficiency of essential trace elements such as calcium, iron and zinc and various vitamins, leading to malnutrition and growth retardation, but also the immune function of the body will be weakened.

[0003] The oral liquid becomes an ideal dosage form for children to supplement nutrition and regulate the spleen and stomach because of its accurate dosage, convenient taking and relatively easy-to-accept taste. At present, there are some oral liquid products for digestion and accumulation or supplement of trace elements on the market, but usually the digestion and accumulation function is single or the efficacy is insufficient, which is difficult to effectively improve the indigestion and poor appetite, and difficult to fundamentally solve the problem of nutrient absorption disorder. On the other hand, some products directly add Chinese medicinal ingredients with bad taste or odor residues (such as mineral taste and medicinal taste), which can easily aggravate the resistance of children to the oral liquid, resulting in poor compliance and further affecting the treatment effect. SUMMARY

[0004] In order to solve the above technical defects, the present application researches an oral liquid for digestion and accumulation and supplement of calcium, iron and zinc and a preparation method thereof, which can effectively strengthen the digestion and accumulation function while ensuring the stability of the oral liquid through diet therapy and aromatherapy, so as to improve the indigestion and anorexia of children.

[0005] A preparation method of an oral liquid for digestion and accumulation and supplement of calcium, iron and zinc, comprising the following steps: S1: extraction and purification of wind flower vegetable polysaccharide After the fresh and disease-free wind flower vegetable tender shoots are washed, dried and crushed, water extraction is carried out, the obtained polysaccharide concentrate is deproteinized and alcohol precipitated, the wind flower vegetable crude polysaccharide obtained by centrifugation is chromatographed by DEAE cellulose DE-52 column to obtain wind flower vegetable polysaccharide; S2: preparation of auxiliary digestion agent The wind flower vegetable polysaccharide is dissolved in distilled water, the pH is adjusted to 9, acetic anhydride is added for stirring reaction, then the pH is adjusted to neutral, dialysis is carried out with deionized water, and acetylated wind flower vegetable polysaccharide is obtained by freeze-drying. The acetylated wind flower vegetable polysaccharide is added into the mixed concentrate obtained by water extraction and decoction of hawthorn, coix seed and yam to obtain an auxiliary digestion agent; S3: preparation of aromatic digestion agent The fresh chopped Pu'er tea leaves and fresh Pogostemonis Herba leaves are extracted by steam extraction method to obtain a mixed volatile oil of Pu'er and Pogostemonis Herba, food-grade ammonium bicarbonate and hydroxypropyl-β-cyclodextrin are mixed uniformly, then the mixed volatile oil of Pu'er and Pogostemonis Herba is slowly added under the condition of 55-60℃ and 600-650rpm stirring speed, and after the addition is completed, centrifugation and reduced pressure drying are performed to obtain the aromatic digestion agent; S4: compounding of oral liquid Chitosan is added to the auxiliary digestion agent for flocculation to obtain a clarified auxiliary digestion agent, zinc gluconate, calcium gluconate, ferrous gluconate and honey are dissolved in purified water to obtain a calcium iron zinc supplement sweetener, and the clarified auxiliary digestion agent, the calcium iron zinc supplement sweetener, the aromatic digestion agent and potassium sorbate are mixed uniformly, then the oral liquid of digestion and accumulation calcium iron zinc supplement is obtained after liquid supplementing, filling, sterilization and the like.

[0006] Further, the extraction and purification of the windflower polysaccharide in step S1 specifically include the following steps: S1.1: Fresh and disease-free windflower seedlings are washed and dried at 45-50℃, then ground to 100-110 mesh, and windflower powder is obtained, the windflower powder and distilled water are mixed uniformly at a mass ratio of 1: (30-40), boiled at 75-80℃ for 2.5-3h, then filtered, and the filtrate is concentrated under reduced pressure to 20-25% of the original volume to obtain a polysaccharide concentrate; S1.2: The polysaccharide concentrate is added with a n-butanol-chloroform mixed solvent, shaken thoroughly for 25-30min, then centrifuged at a speed of 3000-4000rpm for 10-15min, the supernatant is taken and added with 3-4 times the volume of anhydrous ethanol, and the mixture is placed at 4℃ overnight, then centrifuged to collect the precipitate, which is dried at 40-45℃ to obtain crude windflower polysaccharide; S1.3: The crude windflower polysaccharide is dissolved in distilled water to prepare a crude polysaccharide solution with a concentration of 5-6mg / mL, then injected into a DEAE cellulose DE-52 column, the column is eluted with distilled water, the filtrate is collected, concentrated to 10-15% of the original volume, and then freeze-dried at -40 to -50℃ to obtain windflower polysaccharide.

[0007] Further, the preparation of the auxiliary digestion agent in step S2 specifically includes the following steps: S2.1: Dissolve the polysaccharide of Zostera marina L. in distilled water at a solid-liquid ratio of 1: (40-45) g / mL, then add NaOH to adjust the pH of the solution to 9, stir for 10-15 min, add 3-5 mL of acetic anhydride drop by drop while maintaining the pH at 9, and stir for 30-35 min after the addition of acetic anhydride is complete. After adjusting the pH to neutral, place the solution in a dialysis bag and dialyze it with deionized water. Then take out the solution in the dialysis bag and freeze-dry it in a freeze-dryer to obtain acetylated Zostera marina L. polysaccharide; S2.2: Place hawthorn, coix seed and yam in a container at a mass ratio of 1: (0.5-1): (0.5-1), add 25-30 times the mass of distilled water, and then cook at 80-85°C for 2-3 h. Then filter the filtrate, concentrate to a relative density of 1.08-1.1, and obtain a mixed concentrate. Add 4-5 wt% of acetylated Zostera marina L. polysaccharide to the mixed concentrate, stir until the acetylated Zostera marina L. polysaccharide is completely dissolved, and obtain an auxiliary food digestant.

[0008] Further, the preparation of the aromatic food digestant in step S3 specifically includes the following steps: S3.1: Take fresh tender Pu'er tea leaves and fresh pachouli leaves at a mass ratio of 1: (1-1.2), wash them with water to remove impurities, then dry them in the shade and cut them into strips with a width of 0.5-1 cm. Then soak the strips in distilled water for 10-20 min to obtain pretreated leaves. Place the pretreated leaves in a volatile oil extraction container and perform dry steaming on the pretreated leaves by introducing steam from the bottom of the extraction container. Control the temperature in the volatile oil extraction container at 95-100°C. Collect the steam passing through the pretreated leaves by a condensation device at 20-25°C to obtain a distillate. Let the distillate stand to separate into layers, collect the upper oily liquid, and obtain a Pu'er-pachouli mixed volatile oil. S3.2: Mix 2-3 parts by weight of food-grade ammonium bicarbonate and 18-20 parts by weight of hydroxypropyl-β-cyclodextrin uniformly, then add 300-350 parts by weight of distilled water at 20-25°C, and stir at a speed of 300-350 rpm until clear to obtain an inclusion solution. Slowly add 2-3 parts by weight of the Pu'er-pachouli mixed volatile oil to the inclusion solution at 55-60°C and a stirring speed of 600-650 rpm, and the addition time is 30-35 min to obtain a suspension. S3.3: Centrifuge the suspension in a centrifuge at 4000-5000 rpm for 15-20 min, collect the precipitate, and dry it at 65-70°C under reduced pressure to obtain an aromatic food digestant.

[0009] Further, the compounding of the oral liquid in step S4 specifically includes the following steps: S4.1: add chitosan in the auxiliary food digestant and stir uniformly, filter with a plate and frame filter 600 mesh filter paper after flocculation, and obtain a clarified auxiliary food digestant; S4.2: dissolve 0.08-0.1 parts by weight of zinc gluconate, 0.08-0.1 parts by weight of calcium gluconate, 0.08-0.1 parts by weight of ferrous gluconate and 1-2 parts by weight of honey in 3-5 parts by weight of purified water, and obtain a calcium iron zinc supplement sweetener; S4.3: mix 30-42 parts by weight of the clarified auxiliary food digestant, 24-30 parts by weight of the calcium iron zinc supplement sweetener, 4-6 parts by weight of the aromatic food digestant and 0.08-0.1 parts by weight of potassium sorbate uniformly, add purified water to supplement liquid to 100 parts by weight, then fill every 10 mL, and place in a 115 DEG C sterilization cabinet for 30 min sterilization, and obtain the food digestant and accumulation supplement oral liquid.

[0010] Further, the n-butanol-chloroform mixed solvent in step S1.2 is prepared by mixing n-butanol and chloroform at a volume ratio of 1:5, and the n-butanol-chloroform mixed solvent accounts for 20-25% of the volume of the polysaccharide concentrated solution.

[0011] Further, the molecular weight cut-off of the dialysis bag in step S2.1 is 8000-10000 Da.

[0012] Further, the dialysis time in step S2.1 is 2-3 days, and the deionized water is replaced every 8-12 hours of dialysis.

[0013] Further, the amount of chitosan added in step S4.1 accounts for 2-3 wt% of the auxiliary food digestant, the flocculation temperature is 30-35 DEG C, and the flocculation time is 4-5 h.

[0014] A food digestant and accumulation supplement oral liquid is prepared by the preparation method of the food digestant and accumulation supplement oral liquid.

[0015] The beneficial effects are: 1. The water extraction and alcohol precipitation are used to extract the zephyranthes grandiflora crude polysaccharide from the zephyranthes grandiflora, then the DEAE cellulose DE-52 column is used for chromatography to prepare the zephyranthes grandiflora polysaccharide, the zephyranthes grandiflora polysaccharide is acetylated to prepare the acetylated zephyranthes grandiflora polysaccharide, which can promote the proliferation activity of beneficial bacteria in the human intestinal tract and inhibit the reproduction of harmful bacteria, and the mixed concentrated solution obtained by water extraction and concentration of hawthorn, coix seed and yam is compounded, the prepared auxiliary food digestant applied in the oral liquid can strengthen the effect of food digestion and accumulation, promote the absorption and utilization of effective components of food by the body, thereby effectively improving the treatment of human dyspepsia, improving the appetite of children, eliminating malnutrition and immune decline caused by dyspepsia and poor appetite.

[0016] 2. This application uses steam extraction to co-extract volatile oil components from fresh tender Pu-erh tea leaves and fresh patchouli leaves to obtain a Pu-erh-patchouli mixed volatile oil. This Pu-erh-patchouli mixed volatile oil is then formulated into an aromatic digestive aid and added to an oral liquid. The fresh woody and ripe fruity aroma of the Pu-erh volatile oil, combined with the woody, herbal, and spicy aroma of the patchouli volatile oil, creates different layers of fragrance. After taking the oral liquid, which aids digestion, relieves stagnation, and supplements calcium, iron, and zinc, the residual aroma effectively invigorates the spleen and improves digestion and appetite in children.

[0017] 3. In this application, ammonium bicarbonate and hydroxypropyl-β-cyclodextrin are mixed and used to encapsulate the volatile oil of Pu-erh tea and patchouli. During the encapsulation process of hydroxypropyl-β-cyclodextrin with the volatile oil of Pu-erh tea and patchouli, ammonium bicarbonate continuously decomposes at a temperature of 55-60℃ to generate microbubbles, creating numerous microchannels on the wall material of hydroxypropyl-β-cyclodextrin. These microchannels allow the gas molecules of the volatile oil of Pu-erh tea and patchouli to dissipate while ensuring that the oil cannot pass through. This prevents the volatile oil from seeping into the oral liquid, causing stratification and a deterioration in taste. At the same time, it allows the special aroma of the volatile oil of Pu-erh tea and patchouli to dissipate, preventing the taste of the oral liquid from affecting the palate and causing further loss of appetite in children. Detailed Implementation

[0018] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Example 1 A method for preparing an oral liquid that aids digestion, relieves indigestion, and supplements calcium, iron, and zinc includes the following steps: S1: Extraction and purification of polysaccharides from cauliflower S1.1: After cleaning fresh, disease-free cauliflower seedlings, dry them at 45℃ until the moisture content is 5%. Then, crush them and sieve them through a 100-mesh screen to obtain cauliflower powder. Mix the cauliflower powder with distilled water at a mass ratio of 1:30. Boil at 75℃ for 2.5 hours and then filter. Keep the filtrate and concentrate it under reduced pressure to 20% of the original volume to obtain polysaccharide concentrate. S1.2: Add n-butanol-chloroform mixed solvent to the polysaccharide concentrate, the n-butanol-chloroform mixed solvent is prepared by mixing n-butanol and chloroform at a volume ratio of 1:5, the added n-butanol-chloroform mixed solvent accounts for 20% of the volume of the polysaccharide concentrate, fully oscillate for 25 min, then centrifuge at 3000 rpm for 10 min, take the supernatant, repeat the operation until there is no protein precipitate, add 3 times the volume of anhydrous ethanol to the finally obtained supernatant, stand at 4°C overnight, centrifuge to collect the precipitate, and dry at 40°C to obtain the coarse polysaccharide of Codium fragile; S1.3: Dissolve the coarse polysaccharide of Codium fragile in distilled water to prepare a coarse polysaccharide solution with a concentration of 5 mg / mL, then inject it into a DEAE cellulose DE-52 column, elute the column with distilled water, collect the filtrate, concentrate to 10% of the original volume, and freeze-dry at -40°C to obtain the Codium fragile polysaccharide.

[0020] S2: Preparation of auxiliary digestant S2.1: Dissolve the Codium fragile polysaccharide in distilled water at a solid-liquid ratio of 1:40 g / mL, then add NaOH to adjust the solution pH to 9, stir for 10 min, add 3 mL of acetic anhydride dropwise at room temperature and maintain the pH at 9, stir for 30 min after the addition of acetic anhydride is completed, adjust the pH to neutral, then add it into a dialysis bag with a molecular weight cut-off of 8000 Da and dialyze with deionized water, the dialysis time is 2 days, and the deionized water is replaced every 8 hours, then take out the solution in the dialysis bag and freeze-dry in a freeze-dryer to obtain acetylated Codium fragile polysaccharide; S2.2: Put hawthorn, coix seed and yam in a container at a mass ratio of 1:0.5:0.5, add 25 times the mass of distilled water, then cook at 80°C for 2 h, filter to retain the filtrate, concentrate to a relative density of 1.08 to obtain a mixed concentrate, add 4 wt% of acetylated Codium fragile polysaccharide to the mixed concentrate, stir until the acetylated Codium fragile polysaccharide is completely dissolved to obtain an auxiliary digestant.

[0021] S3: Preparation of aromatic digestant S3.1: Take fresh tender Pu'er tea leaves and fresh patchouli leaves at a mass ratio of 1:1, wash with water to remove impurities, then dry in the shade and cut into strips with a width of 0.5 cm, then soak in distilled water for 10 min to obtain pretreated leaves, put the pretreated leaves into a volatile oil extraction container, use steam extraction method, introduce steam from the bottom of the extraction container to dry the pretreated leaves, control the temperature in the volatile oil extraction container at 95°C, the steam passing through the pretreated leaves is collected by a 20°C condensation device to obtain a distillate, let the distillate stand to separate into layers, collect the upper oily liquid to obtain a Pu'er-patchouli mixed volatile oil; S3.2: 2 parts by weight of food-grade ammonium bicarbonate and 18 parts by weight of hydroxypropyl-β-cyclodextrin are mixed uniformly, then 300 parts by weight of distilled water at 20℃ is added, and stirring is carried out at a speed of 300 rpm until it is clear, obtaining an inclusion solution, under the condition of 55℃ and stirring speed of 600 rpm, 2 parts by weight of Pu'er-Huoxiang mixed volatile oil is slowly added into the inclusion solution, the adding time is 30 min, obtaining a suspension; S3.3: The suspension is placed in a centrifuge and centrifuged at 4000 rpm for 15 min, the precipitate is collected and dried under reduced pressure at 65℃, obtaining the aromatic digestion agent.

[0022] S4: Preparation of oral liquid S4.1: Chitosan is added to the auxiliary digestion agent and stirred uniformly and flocculated, the addition amount of chitosan is 2wt% of the auxiliary digestion agent, the flocculation temperature is 30℃, the flocculation time is 4h, then filtered with a plate and frame filter 600 mesh filter paper, obtaining a clear auxiliary digestion agent; S4.2: 0.08 parts by weight of zinc gluconate, 0.08 parts by weight of calcium gluconate, 0.08 parts by weight of ferrous gluconate and 1 part by weight of honey are dissolved in 3 parts by weight of purified water, obtaining a calcium, iron and zinc supplement sweetener; S4.3: 30 parts by weight of clear auxiliary digestion agent, 24 parts by weight of calcium, iron and zinc supplement sweetener, 4 parts by weight of aromatic digestion agent and 0.1 part by weight of potassium sorbate are mixed uniformly, add purified water to 100 parts by weight, then fill each 10mL, and place it in a 115℃ sterilization cabinet for 30min sterilization, obtaining the digestion and accumulation of calcium, iron and zinc oral liquid.

[0023] Example 2 A preparation method of a digestion and accumulation of calcium, iron and zinc oral liquid, specifically comprising the following steps: S1: Extraction and purification of Zephyranthes grandiflora polysaccharide S1.1: Fresh Zephyranthes grandiflora seedlings without disease are washed and dried at 48℃, dried to a moisture content of 6%, then pulverized and sieved to 110 mesh, obtaining Zephyranthes grandiflora powder, which is mixed with distilled water at a mass ratio of 1:35, boiled at 78℃ for 2.8h, then filtered, and the filtrate is concentrated under reduced pressure to 23% of the original volume, obtaining a polysaccharide concentrate; S1.2: Add n-butanol-chloroform mixed solvent to the polysaccharide concentrate, the n-butanol-chloroform mixed solvent is prepared by mixing n-butanol and chloroform at a volume ratio of 1:5, the added n-butanol-chloroform mixed solvent accounts for 22% of the volume of the polysaccharide concentrate, fully oscillate for 28 min, then centrifuge at a speed of 3500 rpm for 12 min, take the supernatant, repeat the operation until there is no protein precipitate, add 3.5 times the volume of anhydrous ethanol to the finally obtained supernatant, stand at 4°C overnight, centrifuge to collect the precipitate, and dry at 42°C to obtain the coarse polysaccharide of Zostera marina; S1.3: Dissolve the coarse polysaccharide of Zostera marina in distilled water to prepare a coarse polysaccharide solution with a concentration of 5.5 mg / mL, then inject it into a DEAE cellulose DE-52 column, elute the column with distilled water, collect the filtrate, concentrate to 12% of the original volume, and freeze-dry at -45°C to obtain the polysaccharide of Zostera marina.

[0024] S2: Preparation of auxiliary digestant S2.1: Dissolve the polysaccharide of Zostera marina in distilled water at a solid-liquid ratio of 1:43 g / mL, then add NaOH to adjust the pH of the solution to 9, stir for 12 min, add 4 mL of acetic anhydride dropwise at room temperature and maintain the pH at 9, stir for 33 min after the addition of acetic anhydride is completed, adjust the pH to neutral, then add a dialysis bag with a molecular weight cut-off of 9000 Da and dialyze with deionized water, the dialysis time is 2.5 days, and the deionized water is replaced every 10 hours, then take out the solution in the dialysis bag and freeze-dry in a freeze-dryer to obtain acetylated polysaccharide of Zostera marina; S2.2: Put hawthorn, coix seed and yam in a container at a mass ratio of 1:0.8:0.8, add 27 times the mass of distilled water, then cook at 82°C for 3 h, then filter to retain the filtrate, concentrate to a relative density of 1.09 to obtain a mixed concentrate, add 4.5 wt% of acetylated polysaccharide of Zostera marina to the mixed concentrate, stir until the acetylated polysaccharide of Zostera marina is completely dissolved to obtain an auxiliary digestant.

[0025] S3: Preparation of aromatic digestant S3.1: Take fresh tender Pu'er tea leaves and fresh patchouli leaves at a mass ratio of 1:1.1, wash with water to remove impurities, then dry in the shade and cut into strips with a width of 0.8 cm, then soak in distilled water for 15 min to obtain pretreated leaves, put the pretreated leaves into a volatile oil extraction container, use steam extraction method, introduce steam from the bottom of the extraction container to dry the pretreated leaves, control the temperature in the volatile oil extraction container at 97°C, the steam passing through the pretreated leaves is collected by a 23°C condensation device to obtain a distillate, let the distillate stand to separate into layers, collect the upper oily liquid to obtain a Pu'er-patchouli mixed volatile oil; S3.2: 2.5 parts by weight of food-grade ammonium bicarbonate and 19 parts by weight of hydroxypropyl-beta-cyclodextrin were mixed uniformly, then 325 parts by weight of distilled water at 23℃ was added, and stirred at a speed of 325 rpm until clear, to obtain an inclusion solution, under the condition of 58℃ and 625 rpm stirring speed, 2.5 parts by weight of Pu'er-Huoxiang mixed volatile oil was slowly added into the inclusion solution, the adding time was 33 min, to obtain a suspension; S3.3: The suspension was placed in a centrifuge and centrifuged at 4500 rpm for 17 min, the precipitate was collected and dried under reduced pressure at 68℃ to obtain the aromatic digestion agent.

[0026] S4: Preparation of oral liquid S4.1: Chitosan was added to the auxiliary digestion agent and stirred uniformly and flocculated, the addition amount of chitosan was 2.5wt% of the auxiliary digestion agent, the flocculation temperature was 32℃, the flocculation time was 4.5h, then filtered with a plate and frame filter 600 mesh filter paper to obtain a clear auxiliary digestion agent; S4.2: 0.09 parts by weight of zinc gluconate, 0.09 parts by weight of calcium gluconate, 0.09 parts by weight of ferrous gluconate and 1.5 parts by weight of honey were dissolved in 4 parts by weight of purified water to obtain a calcium, iron and zinc supplement sweetener; S4.3: 36 parts by weight of clear auxiliary digestion agent, 27 parts by weight of calcium, iron and zinc supplement sweetener, 5 parts by weight of aromatic digestion agent and 0.15 parts by weight of potassium sorbate were mixed uniformly, purified water was added to 100 parts by weight, then filled every 10mL, and placed in a 115℃ sterilization cabinet for 30min sterilization to obtain a digestion and accumulation supplementing calcium, iron and zinc oral liquid.

[0027] Example 3 A preparation method of a digestion and accumulation supplementing calcium, iron and zinc oral liquid, specifically comprising the following steps: S1: Extraction and purification of Zephyranthes grandiflora polysaccharide S1.1: Fresh Zephyranthes grandiflora seedlings without disease were washed and dried at 50℃, then pulverized and sieved to 110 mesh to obtain Zephyranthes grandiflora powder, which was mixed with distilled water at a mass ratio of 1:40, boiled at 80℃ for 3h, then filtered, and the filtrate was concentrated under reduced pressure to 25% of the original volume to obtain a polysaccharide concentrate; S1.2: Add n-butanol-chloroform mixed solvent to the polysaccharide concentrate, the n-butanol-chloroform mixed solvent is prepared by mixing n-butanol and chloroform at a volume ratio of 1:5, the added n-butanol-chloroform mixed solvent accounts for 25% of the volume of the polysaccharide concentrate, fully oscillate for 30 min, then centrifuge at 4000 rpm for 15 min, take the supernatant, repeat the operation until there is no protein precipitate, add 4 times the volume of anhydrous ethanol to the finally obtained supernatant, stand at 4°C overnight, centrifuge to collect the precipitate, and dry at 45°C to obtain the coarse polysaccharide of Codium fragile; S1.3: Dissolve the coarse polysaccharide of Codium fragile in distilled water to prepare a coarse polysaccharide solution with a concentration of 6 mg / mL, then inject it into a DEAE cellulose DE-52 column, elute the column with distilled water, collect the filtrate, concentrate to 15% of the original volume, and freeze-dry at -50°C to obtain the Codium fragile polysaccharide.

[0028] S2: Preparation of auxiliary digestant S2.1: Dissolve the Codium fragile polysaccharide in distilled water at a solid-liquid ratio of 1:45 g / mL, then adjust the pH of the solution to 9 by adding NaOH, stir for 15 min, add 5 mL of acetic anhydride dropwise at room temperature and maintain the pH at 9, stir for 35 min after the addition of acetic anhydride is completed, adjust the pH to neutral, then add it into a dialysis bag with a molecular weight cut-off of 10000 Da and dialyze it with deionized water, the dialysis time is 3 days, and the deionized water is replaced every 12 hours, then take out the solution in the dialysis bag and freeze-dry it in a freeze-dryer to obtain acetylated Codium fragile polysaccharide; S2.2: Put hawthorn, coix seed and yam in a container at a mass ratio of 1:1:1, add 30 times the mass of distilled water, then cook at 85°C for 3 h, then filter to retain the filtrate, concentrate to a relative density of 1.1 to obtain a mixed concentrate, add 5 wt% of acetylated Codium fragile polysaccharide to the mixed concentrate, stir until the acetylated Codium fragile polysaccharide is completely dissolved to obtain an auxiliary digestant.

[0029] S3: Preparation of aromatic digestant S3.1: Take fresh tender Pu'er tea leaves and fresh patchouli leaves at a mass ratio of 1:1.2, wash with water to remove impurities, then dry in the shade and cut into strips with a width of 1 cm, then soak in distilled water for 20 min to obtain pretreated leaves, put the pretreated leaves into a volatile oil extraction container, use steam extraction method, introduce steam from the bottom of the extraction container to dry the pretreated leaves, control the temperature in the volatile oil extraction container at 100°C, the steam passing through the pretreated leaves is collected by a 25°C condensation device to obtain a distillate, let the distillate stand to separate into layers, collect the upper oily liquid to obtain a Pu'er-patchouli mixed volatile oil; S3.2: Mix 3 parts by weight of food-grade ammonium bicarbonate and 20 parts by weight of hydroxypropyl-β-cyclodextrin evenly, then add 350 parts by weight of distilled water at 25°C, and stir at 350 rpm until clear to obtain an inclusion solution. Under the conditions of 60°C and 650 rpm stirring speed, slowly add 3 parts by weight of Pu-erh tea-patchouli mixed volatile oil to the inclusion solution at the same time for 35 min to obtain a suspension. S3.3: Place the suspension in a centrifuge and centrifuge at 5000 rpm for 20 min. Collect the precipitate and dry it under reduced pressure at 70℃ to obtain the aromatic digestive agent.

[0030] S4: Compound oral liquid S4.1: Add chitosan to the digestive aid, stir evenly, and allow it to stand and flocculate. The amount of chitosan added is 3wt% of the digestive aid. The flocculation temperature is 35℃ and the flocculation time is 5h. Then filter it with 600-mesh plate and frame filter paper to obtain a clear digestive aid. S4.2: Dissolve 0.1 parts by weight of zinc gluconate, 0.1 parts by weight of calcium gluconate, 0.1 parts by weight of ferrous gluconate and 2 parts by weight of honey in 5 parts by weight of purified water to obtain a calcium, iron and zinc supplement sweetener; S4.3: Mix 42 parts by weight of clarifying digestive aid, 30 parts by weight of calcium, iron and zinc supplement sweetener, 6 parts by weight of aromatic digestive aid and 0.2 parts by weight of potassium sorbate evenly, add purified water to make up to 100 parts by weight, then fill into 10 mL vials and sterilize in a 115℃ sterilizer for 30 min to obtain an oral liquid for digestion, calcium, iron and zinc supplementation.

[0031] Comparative Example 1 Steps S1 and S2.1 are removed. In the preparation of the digestive aid in step S2, the acetylated cauliflower polysaccharide in step S2.2 is replaced with an equal mass of hawthorn polysaccharide. The remaining formula and preparation steps are the same as in Example 1.

[0032] Comparative Example 2 In the preparation of the aromatic digestive agent in step S3, the fresh tender Pu-erh tea leaves in step S3.1 are replaced with an equal mass of fresh patchouli leaves, and the rest of the formula and preparation steps are the same as in Example 1.

[0033] Comparative Example 3 In the preparation of the aromatic digestive agent in step S3, the fresh patchouli leaves in step S3.1 are replaced with an equal mass of fresh tender Pu-erh tea leaves, and the rest of the formula and preparation steps are the same as in Example 1.

[0034] Comparative Example 4 In the preparation of the aromatic food digestant in step S3, the food-grade ammonium bicarbonate in step S3.2 is replaced by an equal amount of hydroxypropyl-β-cyclodextrin, and the rest of the formulation and preparation steps are the same as in Example 1.

[0035] Experiment One: Take the oral solution prepared in Examples 1-3 and Comparative Example 4, 10 pieces per group, and place them in a 40°C, 75% relative humidity environment for 3 months. At the end of the 1st, 2nd, and 3rd months, observe whether the oral solution in each group appears turbid and the oil phase separates, and then select one piece for odor discrimination to determine its fragrance. The results are shown in Table 1.

[0036] Table 1: Turbidity and fragrance of oral solution after 3 months of storage

[0037] As can be seen from the phenomena of Examples 1-3 in Table 1 after 3 months of storage, the oral solution prepared in this application for digesting and accumulating calcium, iron, and zinc has good stability, and has a fresh woody and herbal aroma. Comparative Example 4 did not add food-grade ammonium bicarbonate during the inclusion of the volatile oil, and its fragrance was not obvious, which proves that the aromatic food digestant prepared in this application can prevent volatile oil from penetrating into the oral solution, causing the oral solution to separate and the taste to deteriorate, but at the same time can allow the special fragrance of Pu'er volatile oil and Guanghuoxiang volatile oil to be released, playing the role of aromatic therapy for digestion.

[0038] Experiment Two: Select 30 SD rats and then randomly divide them into 3 groups, 10 rats per group. On the basis of normal feeding of the SD rats, use the oral solution prepared in Example 1 and Comparative Example 1 to respectively perform gavage on one group of SD rats, with a gavage amount of 1 mL / d, and the remaining group of rats is set as a blank group, which is only normally fed every day. After 21 days of feeding, 5 mice are randomly selected from each group and sacrificed, then the feces from the cecum of each group are aseptically collected in 2 mL sterile tubes for high-throughput sequencing of intestinal flora, and the test results are shown in Table 2.

[0039] Table 2: Abundance of each bacterial species in the intestinal flora of mice after 14 days of feeding

[0040] (mean ± standard deviation, different letters in the same row indicate significant differences between groups (p<0.05), and the same letter indicates no significant difference) As can be seen from the data of Table 2, Example 1 and Comparative Example 1, the oral liquid prepared in Example 1 has obvious inhibitory effect on the proliferation of harmful bacteria such as Proteobacteria, Staphylococcus, Enterococcus and Bacteroidetes, and can enhance the proliferation activity of beneficial bacteria such as Firmicutes and Lactobacillus, thereby promoting the digestive and absorptive capacity of the intestinal tract. In Comparative Example 1, acetylated Sargassum muticum polysaccharide is replaced by hawthorn polysaccharide of the same mass, and the oral liquid prepared therefrom has lower inhibitory effect on the proliferation of harmful bacteria and lower effect of enhancing the proliferation activity of beneficial bacteria than Example 1, which can prove that acetylated Sargassum muticum polysaccharide can inhibit the proliferation of harmful bacteria by promoting the proliferation activity of beneficial bacteria.

[0041] Experiment Three: 90 SD male rats weighing between 110-130 g were selected, and after adaptive feeding for 3 days, the 90 rats were randomly divided into 9 groups, 10 rats in each group. The oral liquids prepared in Examples 1-3 and Comparative Examples 1-4 and distilled water were used to gavage each group of rats, one kind of oral liquid corresponding to one group of rats, distilled water corresponding to one group of rats as a blank group, and commercially available Jianwei Xiaoshi oral liquid corresponding to one group of rats as a control group. The gavage dose was 1 mL / d, and the gavage was continuously performed for 28 d. During the experiment, the rats were normally fed to ensure that the living environment of the rats was clean.

[0042] Body weight test: the initial average body weight, the average body weight at the 4th week, and the body weight change amount of each group of rats were calculated and recorded, and the results are shown in Table 3.

[0043] Table 3: Body weight change of rats

[0044] Experiment Four: 90 Kunming mice were selected, 10 mice in each group, and the mice were fasted but not water-deprived. The oral liquids prepared in Examples 1-3 and Comparative Examples 1-4, distilled water, and Jianwei Xiaoshi oral liquid were used to gavage each group of mice. The distilled water group was set as a blank group, and the commercially available Jianwei Xiaoshi oral liquid group was set as a control group. After gavage at a dose of 0.2 mL for 1 h, 0.2 mL of each group of oral liquid containing 10% carbon powder was orally administered, and the mice were sacrificed by cervical dislocation after 20 min. The intestinal canal from the pylorus to the end of the ileum was quickly taken out and straightened, and the length from the pyloric sphincter to the front end of the carbon powder and the length from the pyloric sphincter to the ileocecal junction were measured, respectively.

[0045] The small intestinal propulsion rate was calculated as (length from the pyloric sphincter to the front end of the carbon powder / length from the pyloric sphincter to the ileocecal junction) x 100%, and the small intestinal propulsion rate of each group of mice was averaged, and the results are shown in Table 4.

[0046] Table 4: Small intestinal propulsion rate of mice after administration

[0047] From the data of Table 3 and Table 4 of Examples 1-3, it can be seen that the oral liquid prepared by the application for promoting digestion and treating food accumulation can promote small intestine movement, thereby effectively strengthening the effect of promoting digestion and treating food accumulation, and is stronger than the effect of promoting digestion of the stomachic oral liquid in the market.

[0048] From Comparative Example 1, it can be seen that when the acetylated polysaccharide of windflower is not added, the digestion function is obviously decreased, which can prove that the acetylated polysaccharide of windflower can inhibit the proliferation of harmful bacteria by promoting the proliferation of beneficial bacteria, thereby strengthening the effect of promoting digestion and treating food accumulation, promoting the absorption and utilization of effective components of food by the body, and thereby effectively improving the problem of human dyspepsia.

[0049] From the data of Comparative Example 2 and Comparative Example 3, it can be seen that Pu'er volatile oil and patchouli volatile oil have a synergistic effect, and the two can synergistically perform aroma therapy, thereby promoting digestion and improving the problem of dyspepsia.

[0050] From the data of Comparative Example 4, it can be seen that the application mixes ammonium bicarbonate and hydroxypropyl-β-cyclodextrin and performs inclusion treatment on the mixed volatile oil of Pu'er and patchouli, and the small channels can make the gas molecules of Pu'er volatile oil and patchouli volatile oil dissipate, thereby ensuring the effectiveness of aroma therapy.

[0051] Experiment Five: HepG2 cells and Caco-2 cells were inoculated into 96-well plates, respectively, and the culture solution was DEME culture solution containing 10% fetal bovine serum, 1% non-essential amino acids and 1% L-glutamine, and the cell concentration was adjusted to 1×10 4 / mL, then cultured in a 37℃ incubator with 5% CO2 for 12h, then 2μL of DEME culture solution containing 30% of the oral liquid for promoting digestion and treating food accumulation prepared in Examples 1-3 was added, and negative control wells (culture solution without the oral liquid for promoting digestion and treating food accumulation) and blank zero wells (the final concentration of DMSO in each well was 0.1%) were set, and then cultured for 48h.

[0052] The culture solution in each well was aspirated, 20μL of 5mg / mL MTT solution was added, and then cultured for 4h, after the supernatant was discarded, 150μL of DMSO was used to shake for 10min to dissolve the crystals, and then the optical density (OD) value was measured at 490nm by an enzyme marker, the MTT method was used to judge the effect of the oral liquid for promoting digestion and treating food accumulation on the proliferation of HepG2 cells and Caco-2 cells, and the cell survival rate (%) = (OD value of the drug administration well / OD value of the negative control well) ×100%, and the results are shown in Table 5.

[0053] Table 5: Cell survival rate after treatment with oral liquid

[0054] As can be seen from the data of Examples 1-3 in Table 5, after the culture solution to which the prepared oral liquid of the calcium, iron and zinc supplement for food digestion and accumulation is added is used to culture and treat HepG2 cells and Caco-2 cells, the survival rates of the HepG2 cells and the Caco-2 cells are both higher than 96%, which can prove that the prepared oral liquid of the calcium, iron and zinc supplement for food digestion and accumulation has no cytotoxicity and is suitable for human body to take.

[0055] The above examples only illustrate the principles and effects of the present application, and are not intended to limit the present application. Any modification or change made by any person skilled in the art without departing from the spirit and scope of the present application shall be covered by the claims of the present application.

Claims

1. A method for preparing a calcium, iron and zinc supplement oral liquid for food digestion and accumulation, characterized in that, Comprise the following steps: S1: extraction and purification of polysaccharide from Zostera marina L. Fresh Zostera marina L. seedlings without disease were washed, dried and crushed, then water extraction was carried out, and the obtained polysaccharide concentrate was deproteinized and alcohol precipitated. The obtained Zostera marina L. crude polysaccharide was collected by centrifugation and subjected to DEAE cellulose DE-52 column chromatography to obtain Zostera marina L. polysaccharide; S2: preparation of auxiliary food digestant The Zostera marina L. polysaccharide was dissolved in distilled water, the pH was adjusted to 9, acetic anhydride was added and stirred, then it was adjusted to neutral and dialyzed with deionized water, and acetylated Zostera marina L. polysaccharide was obtained by freeze-drying. The acetylated Zostera marina L. polysaccharide was added to the mixed concentrate obtained by water extraction and boiling of hawthorn, coix seed and yam to obtain an auxiliary food digestant; S3: preparation of aromatic food digestant The fresh chopped Pu'er tea leaves and fresh patchouli leaves were subjected to steam extraction to extract volatile oil to obtain Pu'er-patchouli mixed volatile oil. Food-grade ammonium bicarbonate and hydroxypropyl-β-cyclodextrin were mixed uniformly, then the Pu'er-patchouli mixed volatile oil was slowly added under the conditions of 55-60℃ and 600-650rpm stirring speed. After the addition was completed, centrifugation and reduced pressure drying were carried out to obtain an aromatic food digestant; S4: compounding of oral solution The auxiliary food digestant was flocculated by adding chitosan to obtain a clear auxiliary food digestant. Zinc gluconate, calcium gluconate, ferrous gluconate and honey were dissolved in purified water to obtain a calcium, iron and zinc supplement. The clear auxiliary food digestant, the calcium, iron and zinc supplement, the aromatic food digestant and potassium sorbate were mixed uniformly, then the solution was supplemented, filled, sterilized to obtain a food digestant for treating food accumulation and supplementing calcium, iron and zinc.

2. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 1, characterized in that, Step S1 for extraction and purification of polysaccharide from Zostera marina L., specifically comprising the following steps: S1.1: The fresh Zostera marina L. seedlings without disease were washed and dried at 45-50℃, then crushed to pass through a 100-110 mesh sieve to obtain Zostera marina L. powder. The Zostera marina L. powder was mixed with distilled water at a mass ratio of 1: (30-40), then boiled at 75-80℃ for 2.5-3h, filtered, and the filtrate was concentrated under reduced pressure to 20-25% of the original volume to obtain a polysaccharide concentrate; S1.2: The polysaccharide concentrate was added with a mixture of n-butanol-chloroform, shaken thoroughly for 25-30min, then centrifuged at 3000-4000rpm for 10-15min. The supernatant was collected, and the operation was repeated until no protein precipitate was obtained. The obtained supernatant was added with 3-4 times the volume of anhydrous ethanol, and the mixture was placed at 4℃ overnight. The precipitate was collected by centrifugation and dried at 40-45℃ to obtain Zostera marina L. crude polysaccharide; S1.3: The Zostera marina L. crude polysaccharide was dissolved in distilled water to prepare a crude polysaccharide solution with a concentration of 5-6mg / mL, then injected into a DEAE cellulose DE-52 column. The column was eluted with distilled water, and the filtrate was collected, concentrated to 10-15% of the original volume, and freeze-dried at -40 to -50℃ to obtain Zostera marina L. polysaccharide.

3. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 2, characterized in that, Step S2 for preparation of auxiliary food digestant, specifically comprising the following steps: S2.1: dissolve the polysaccharide of Zostera marina L. in distilled water at a solid-liquid ratio of 1: (40-45) g / mL, then add NaOH to adjust the pH of the solution to 9, stir for 10-15 min, add 3-5 mL of acetic anhydride drop by drop at room temperature and maintain the pH at 9, stir for 30-35 min after the addition of acetic anhydride is completed, adjust the pH to neutral, then put the solution in a dialysis bag and dialyze with deionized water, then take out the solution in the dialysis bag and freeze-dry in a freeze dryer to obtain acetylated Zostera marina L. polysaccharide; S2.2: put hawthorn, coix seed and yam in a container at a mass ratio of 1: (0.5-1): (0.5-1), add 25-30 times the mass of distilled water, then cook at 80-85℃ for 2-3h, then filter to retain the filtrate, concentrate to a relative density of 1.08-1.1 to obtain a mixed concentrate, add 4-5wt% acetylated Zostera marina L. polysaccharide to the mixed concentrate, stir until the acetylated Zostera marina L. polysaccharide is completely dissolved to obtain an auxiliary food digestant.

4. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 3, characterized in that, Step S3 for preparing the aromatic food digestant, specifically comprising the following steps: S3.1: take fresh tender Pu'er tea leaves and fresh plectranthus amboinicus leaves at a mass ratio of 1: (1-1.2), wash with water to remove impurities, then dry in the shade and cut into strips with a width of 0.5-1cm, then soak in distilled water for 10-20min to obtain pretreated leaves, put the pretreated leaves in a volatile oil extraction container, use steam extraction method to dry the pretreated leaves by passing steam from the bottom of the extraction container, control the temperature in the volatile oil extraction container at 95-100℃, and collect the steam passing through the pretreated leaves by a 20-25℃ condensing device to obtain a distillate, let the distillate stand to separate into layers, collect the upper oily liquid to obtain a Pu'er-plectranthus amboinicus mixed volatile oil; S3.2: mix 2-3 parts by weight of food-grade ammonium bicarbonate and 18-20 parts by weight of hydroxypropyl-β-cyclodextrin uniformly, then add 300-350 parts by weight of 20-25℃ distilled water, stir at a speed of 300-350rpm until clear to obtain an inclusion solution, slowly add 2-3 parts by weight of Pu'er-plectranthus amboinicus mixed volatile oil to the inclusion solution at 55-60℃ and a stirring speed of 600-650rpm, and the addition time is 30-35min to obtain a suspension; S3.3: centrifuge the suspension in a centrifuge at 4000-5000rpm for 15-20min, collect the precipitate and dry at 65-70℃ under reduced pressure to obtain an aromatic food digestant.

5. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 4, characterized in that, Step S4 for compounding the oral liquid, specifically comprising the following steps: S4.1: add chitosan to the auxiliary food digestant and stir uniformly, let it stand and flocculate, then filter with a plate and frame filter 600 mesh filter paper to obtain a clear auxiliary food digestant; S4.2: dissolve 0.08-0.1 parts by weight of zinc gluconate, 0.08-0.1 parts by weight of calcium gluconate, 0.08-0.1 parts by weight of ferrous gluconate and 1-2 parts by weight of honey in 3-5 parts by weight of purified water to obtain a calcium, iron and zinc supplement sweetener; S4.3: 30-42 parts by weight of the clarified auxiliary digestion agent, 24-30 parts by weight of the calcium, iron and zinc supplement, 4-6 parts by weight of the aromatic digestion agent and 0.08-0.1 parts by weight of potassium sorbate are mixed uniformly, purified water is added to make up to 100 parts by weight, then each 10 mL is filled, and placed in a 115°C sterilization cabinet for 30 min sterilization to obtain the oral liquid of digestion and accumulation of calcium, iron and zinc supplement.

6. The method for preparing an oral liquid for digestion, relieving indigestion, and supplementing calcium, iron, and zinc according to claim 2, characterized in that, The n-butanol-chloroform mixed solvent in step S1.2 is prepared by mixing n-butanol and chloroform at a volume ratio of 1:5, and the n-butanol-chloroform mixed solvent accounts for 20-25% of the volume of the polysaccharide concentrated solution.

7. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 3, characterized in that, The molecular weight cut-off of the dialysis bag in step S2.1 is 8000-10000 Da.

8. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 3, characterized in that, The dialysis time in step S2.1 is 2-3 days, and the deionized water is replaced every 8-12 hours.

9. The method for preparing an oral liquid for digestion, calcium, iron, and zinc supplementation according to claim 5, characterized in that, The addition amount of chitosan in step S4.1 accounts for 2-3 wt% of the auxiliary digestion agent, the flocculation temperature is 30-35°C, and the flocculation time is 4-5 h.

10. A kind of oral liquid of digestion and accumulation of eliminating food, characterized by, It is prepared by the preparation method of the oral liquid of digestion and accumulation of calcium, iron and zinc supplement of any one of claims 1-9.

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