Composition helpful for improving postpartum hypogalactia and improving milk secretion volume and quality

Abstract

According to the composition helpful for improving postpartum hypogalactia and improving milk secretion amount and quality, food raw materials including angelica sinensis, malt, dandelion and day lily serve as main components, extraction is conducted through enzymolysis and ultrasonic processes, and the composition helpful for improving postpartum hypogalactia and improving milk secretion amount and quality is obtained by precisely regulating and controlling the proportion of the angelica sinensis extract, the malt extract, the dandelion extract and the day lily extract. The obtained composition has the effects of improving the postpartum hypogalactia symptom and improving the milk secretion amount and quality.

Description

Technical Field

[0001] This invention relates to the field of compositions, and more specifically to a composition that helps improve postpartum hypogalactia and increase the quantity and quality of breast milk. Background Technology

[0002] Clinically, methods commonly used to promote lactation include physical stimulation, psychological intervention, and drug therapy. Among these, drug therapy is an important means of improving insufficient lactation due to its relatively direct effect. Dopamine receptor antagonists, such as domperidone and metoclopramide, are frequently used clinically. They increase prolactin levels in the body by blocking the inhibitory effect of dopamine on prolactin secretion, thereby promoting lactation. However, these drugs have significant side effects; long-term or improper use may cause gastrointestinal discomfort, dizziness, drowsiness, and other symptoms. Traditional Chinese medicine often uses herbs such as Wang Bu Liu Xing and Tong Cao to improve lactation through the mechanism of "unblocking the lactation channels and promoting qi and blood circulation." However, the composition of these herbs is complex, the effective active ingredients are difficult to identify, quality control is challenging, and long-term use may pose safety risks. Summary of the Invention

[0003] To address the aforementioned problems, the present invention aims to provide a composition that helps improve postpartum hypogalactia and increase the quantity and quality of breast milk. The composition uses food ingredients such as angelica, malt, dandelion, and daylily as main components, and is extracted using enzymatic hydrolysis and ultrasonic processes. By precisely controlling the ratio of angelica extract, malt extract, dandelion extract, and daylily extract, the resulting composition can improve postpartum hypogalactia symptoms and increase the quantity and quality of breast milk.

[0004] The technical solution of the present invention includes: A composition that helps improve postpartum hypogalactia and increase the quantity and quality of breast milk includes Angelica sinensis extract, malt extract, dandelion extract and daylily extract, wherein the mass ratio of Angelica sinensis extract, malt extract, dandelion extract and daylily extract is (0.1-0.3):(0.2-0.6):(0.01-0.03):(40-60).

[0005] Angelica sinensis has the effects of nourishing blood, promoting blood circulation, regulating menstruation, relieving pain, and moistening the intestines to relieve constipation. It can improve postpartum blood deficiency and provide a foundation for the production of qi and blood. Sufficient qi and blood is an important prerequisite for milk production. Although malt is often used to suppress lactation and relieve bloating, its effects of promoting qi circulation, aiding digestion, and strengthening the spleen and stomach can improve the problems of postpartum spleen and stomach weakness and food stagnation. By enhancing the digestive function of the spleen and stomach, it can promote the absorption of nutrients and provide sufficient raw materials for milk production. Dandelion can clear heat and detoxify, reduce swelling and dissipate nodules, and promote urination. It can alleviate the possible postpartum mastitis and prevent the blockage of the mammary ducts caused by inflammation from affecting milk discharge. Daylily is cool in nature and sweet and slightly bitter in taste. It has the effects of clearing heat and promoting diuresis, detoxifying and reducing swelling, nourishing blood and calming the liver. The serotonin it contains can relieve postpartum anxiety and indirectly reduce the inhibition of lactation by negative emotions. At the same time, its blood-nourishing effect can help improve the postpartum body condition.

[0006] As a further improvement to the above scheme, the mass ratio of the Angelica sinensis extract, malt extract, dandelion extract and daylily extract is 0.3:0.6:0.02:40.

[0007] As a further improvement to the above scheme, the Angelica sinensis extract, malt extract, dandelion extract and daylily extract are obtained by enzymatic hydrolysis and ultrasonic treatment of Angelica sinensis, malt, dandelion and daylily, respectively.

[0008] As a further improvement to the above scheme, the enzymatic hydrolysis process includes: using a complex enzyme solution composed of cellulase, pectinase and papain to enzymatically hydrolyze the raw materials, with the hydrolysis temperature being 40~50℃ and the hydrolysis pH being 4.5~5.5.

[0009] As a further improvement to the above scheme, the ultrasonic process includes: mixing the raw material with the extraction solvent, ultrasonically extracting at an ultrasonic frequency of 20~30kHz for 20~70 minutes, and controlling the ultrasonic temperature at 30~50℃.

[0010] As a further improvement to the above scheme, the Angelica sinensis extract, malt extract, dandelion extract, and daylily extract are prepared by the following method: S1. After the raw materials of Angelica sinensis, malt, dandelion and daylily are cleaned, dried, crushed and sieved to obtain raw material powder; S2. The raw material powder is mixed with the compound enzyme solution for enzymatic hydrolysis. The mass ratio of cellulase, pectinase and papain in the compound enzyme solution is 1:1:0.5. The enzymatic hydrolysis temperature is 40~50℃, the enzymatic hydrolysis pH is 4.5~5.5, and the enzymatic hydrolysis time is 30~40min to obtain the enzymatically hydrolyzed raw material. S3. The enzymatically hydrolyzed raw material is mixed with the first extraction solvent and subjected to ultrasonic extraction. The ultrasonic frequency is 20~30kHz, the ultrasonic temperature is controlled at 30~50℃, and the ultrasonic time is 30~40 minutes. After ultrasonic extraction, the mixture is filtered to separate the first extract and the raw material residue. S4. Add a second extraction solvent to the raw material residue and mix for ultrasonic extraction. The volume of the second extraction solvent is 50-70% of the volume of the first extraction solvent. The ultrasonic frequency is 20-30kHz, the ultrasonic temperature is controlled at 30-50℃, and the ultrasonic time is 20-30 minutes. After filtration, the second extract is obtained and combined with the first extract to obtain the raw material extract. S5. The raw material extract is concentrated and dried to obtain the Angelica sinensis extract, malt extract, dandelion extract and daylily extract.

[0011] As a further improvement to the above scheme, in step S3, the first extraction solvent is an ethanol solution with a volume fraction of 10% to 30%, and the ratio of the amount of the first extraction solvent to the raw material powder is 1g:(10~30)ml.

[0012] As a further improvement to the above scheme, the second extraction solvent in step S4 is a 10%~30% volume fraction ethanol solution.

[0013] As a further improvement to the above scheme, the composition further includes excipients or additives that can be used in food or pharmaceuticals, wherein the excipients or additives are at least one of coating agents, sweeteners, antioxidants, thickeners, anti-caking agents and emulsifiers.

[0014] As a further improvement to the above scheme, the coating agent is at least one of carnauba wax, polyethylene glycol, polyvinyl alcohol, mono- and diglyceride fatty acid esters, pullulan, and chitosan.

[0015] As a further improvement to the above scheme, the sweetener is at least one of mogroside, sucralose, erythritol, maltitol, xylitol, sorbitol, steviol glycosides, and neotame.

[0016] As a further improvement to the above scheme, the antioxidant is at least one of calcium ascorbate, propyl gallate, tea polyphenols, ascorbate palmitate, theaflavins, and bamboo leaf antioxidants.

[0017] As a further improvement to the above scheme, the thickener is at least one of gum arabic, pectin, gelatin, potassium alginate, sodium carboxymethyl cellulose, and locust bean gum.

[0018] As a further improvement to the above scheme, the anti-caking agent includes at least one of silicon dioxide, calcium silicate, magnesium stearate, and microcrystalline cellulose.

[0019] As a further improvement to the above scheme, the emulsifier includes at least one of acetylated mono- and diglyceride fatty acid esters, phospholipids, Tween derivatives, and Span derivatives.

[0020] An application of any one of the above compositions includes preparing an oral formulation using the composition as a raw material for at least one of improving postpartum hypogalactia, increasing milk production, and improving milk quality.

[0021] As a further improvement to the above scheme, the oral preparation is one of the following: powder, granules, capsules, tablets, oral solution, and emulsion.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows: Angelica sinensis can nourish blood, promote blood circulation, regulate menstruation, and relieve pain, providing a material basis for milk production, helping to unclog milk ducts, prevent milk stasis, and relieve postpartum breast engorgement caused by poor blood circulation; malt can soothe the liver and regulate qi, allowing milk ducts to flow smoothly and helping milk to be discharged; dandelion can clear heat and detoxify, reduce swelling and dissipate nodules, unclog mild milk stasis, and protect the mammary glands; daylily can nourish blood and soothe the liver, promote diuresis and reduce swelling, and clear heat and detoxify. Its active ingredients, such as alkaloids, flavonoids, and polysaccharides, can regulate endocrine function, improve milk secretion problems from the root, and stimulate the expansion of mammary ducts to promote milk discharge. This invention uses angelica, malt, dandelion, and daylily as main raw materials, and obtains raw material extracts through enzymatic hydrolysis and ultrasonic ethanol extraction. The proportions of each extract are then optimized to obtain a galactagogue composition that improves postpartum hypogalactia and increases the quantity and quality of milk secretion. Experiments have shown that the galactagogue composition prepared in this invention can promote the proliferation of mammary gland cells and lipid production, and has a good effect on improving hypogalactia symptoms in lactating mice. It can increase the milk secretion of hypogalactia-suppressed mice, increase the level of lactation-related hormones, and restore lactation function. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0024] Figure 1 The results show the effect of the lactation-inducing composition on cell viability in the embodiments of the present invention; Figure 2 This is the result of the effect of the lactation-inducing composition on the production of triglycerides in cells in the embodiments of the present invention; Figure 3 This document describes the changes in total milk production during lactation in each group of female mice in the embodiments of the present invention. Figure 4 , Figure 5 This document shows the daily changes in milk production during lactation in each group of female mice in this embodiment of the invention. Figure 6 This describes the weight gain of young mice during the experimental period in this embodiment of the invention. Figure 7 This document describes the lactation-related hormone levels in each group of female mice during lactation, as presented in the embodiments of the present invention.

[0025] Figure labels: A - Experimental group A of galactagogue composition; B - Experimental group B of galactagogue composition; C - Experimental group C of galactagogue composition; D - Experimental group D of galactagogue composition; E - Experimental group E of galactagogue composition; F - Experimental group F of galactagogue composition. Detailed Implementation

[0026] To make the technical problem to be solved, the technical solution, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0027] The weights of the relevant components mentioned in the embodiments of this invention can refer not only to the specific content of each component, but also to the proportional relationship between the weights of the components. Therefore, any scaling up or down of the content of the relevant components according to the embodiments of this invention is within the scope disclosed in the embodiments of this invention. Specifically, the mass described in the embodiments of this invention can be a mass unit known in the chemical industry, such as μg, mg, g, or kg.

[0028] To facilitate understanding of the present invention, the present invention will be described more fully and in detail below with reference to the accompanying drawings and preferred embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0029] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0030] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods. Example 1

[0031] The preparation of Angelica sinensis extract, malt extract, dandelion extract, and daylily extract includes the following steps: S1. Crushing and sieving: The raw materials of Angelica sinensis, malt, dandelion and daylily are rinsed twice with clean water to remove surface dust, mud and residues, so as to avoid introducing impurities during subsequent extraction. After the raw materials are washed, they are dried and then crushed and sieved through a 20-mesh sieve to ensure uniform particle size of the powder, so as to obtain raw material powder. S2. Enzymatic hydrolysis: The raw material powder is mixed with the compound enzyme solution for enzymatic hydrolysis. The compound enzyme solution is prepared as follows: cellulase powder with an enzyme activity of 5000 U / g, pectinase powder with an activity of 1000 U / g, and papain powder with an activity of 100 U / mg are weighed in a ratio of 1:1:0.5, and water is added to prepare a compound enzyme solution with a mass fraction of 10%; the compound enzyme solution is added at a ratio of 0.1% of the mass of the raw material powder, the enzymatic hydrolysis temperature is 40℃, the pH is 4.5, and the enzymatic hydrolysis time is 30 minutes. S3. Single-stage ultrasonic extraction: A 10% volume fraction ethanol solution is used as the first extraction solvent, with a material-to-liquid ratio of 1g:10ml, meaning 10ml of the first extraction solvent is added to 1g of raw material powder; the enzymatically hydrolyzed raw material powder is mixed with the first extraction solvent and then added to an ultrasonic extraction vessel, stirred for 5 minutes, and ultrasonically extracted at a frequency of 20kHz for 40 minutes at an extraction temperature of 30℃; after ultrasonic extraction, the mixture is filtered to separate the extract and raw material residue; S4. Secondary ultrasonic extraction: Add a second extraction solvent to the raw material residue and mix. Then perform ultrasonic extraction. The second extraction solvent is a 20% volume fraction ethanol solution. The volume of the second extraction solvent is 50% of the volume of the first extraction solvent. The ultrasonic frequency is 30kHz, the ultrasonic temperature is 35℃, and the extraction time is 20 minutes. After filtration, combine the two extracts to obtain the raw material extract. S5. Concentration and Drying of Extract: The raw material extract is concentrated using vacuum decompression concentration until solids appear; the solids are dried using spray drying, and the dried powder is passed through an 80-mesh sieve to remove agglomerated particles and ensure uniform particle size, yielding Angelica sinensis extract, malt extract, dandelion extract and daylily extract. Example 2

[0032] The preparation of extracts from Angelica sinensis, malt, dandelion, and daylily includes the following steps: S1. Crushing and sieving: The raw materials of Angelica sinensis, malt, dandelion and daylily are rinsed three times with clean water to remove surface dust, mud and residues, so as to avoid introducing impurities during subsequent extraction. After the raw materials are washed, they are dried and then crushed and sieved through a 40-mesh sieve to ensure uniform particle size of the powder, so as to obtain raw material powder. S2. Enzymatic hydrolysis: The raw material powder is mixed with the compound enzyme solution. The compound enzyme solution is prepared as follows: cellulase powder with an enzyme activity of 5000 U / g, pectinase powder with an activity of 1000 U / g, and papain powder with an activity of 100 U / mg are weighed in a ratio of 1:1:0.5 to prepare a compound enzyme solution with a mass fraction of 10%; the compound enzyme solution is added at a ratio of 0.1% of the mass of the raw material powder, and enzymatic hydrolysis is carried out for 30 minutes at a temperature of 50℃ and a pH of 5.5. S3. Single-stage ultrasonic extraction: Use a 30% volume fraction ethanol solution as the first extraction solvent, and set the material-to-liquid ratio to 1g:30ml, that is, add 30ml of the first extraction solvent to 1g of raw material powder; mix the enzymatically hydrolyzed raw material powder with the first extraction solvent and add it to the ultrasonic extraction vessel, stir for 10 minutes; use an ultrasonic frequency of 30kHz for 40 minutes, and the extraction temperature is 50℃. After ultrasonic extraction, filter while hot to separate the extract and raw material residue. S4. Secondary ultrasonic extraction: Add a second extraction solvent to the raw material residue. The second extraction solvent is a 15% volume fraction ethanol solution. The volume of the second extraction solvent is 80% of the volume of the first extraction solvent. Use an ultrasonic frequency of 25kHz, an extraction temperature of 40℃, and an extraction time of 20 minutes. After filtration, combine the two extracts to obtain the raw material extract. S4. Concentration and Drying of Extract: The raw material extract is concentrated using vacuum decompression concentration until solids appear. The solids are then dried using spray drying. The dried powder is passed through a 100-mesh sieve to remove agglomerated particles and ensure uniform particle size. Angelica extract, malt extract, dandelion extract, and daylily extract are obtained. Example 3

[0033] The Angelica sinensis extract, malt extract, dandelion extract and daylily extract obtained in Example 1 were added to pure water to prepare Angelica sinensis extract solution with a concentration of 0.1 mg / mL, malt extract solution with a concentration of 0.1 mg / mL, dandelion extract solution with a concentration of 0.01 mg / mL and daylily extract solution with a concentration of 10 mg / mL, respectively. They were mixed according to the volume ratio shown in Table 1 to obtain galactagogue compositions A to F.

[0034] Table 1

[0035] Experiment Example 1: CCK-8 Experiment 1. Experimental materials MCF-10A cells were provided by the School of Pharmacy, Central South University. CO2 cell incubator, model MCO-170, brand Songyang; Ultra-clean workbench, model SW-CJ-2FD-11, brand: Sujing Antai; Inverted microscope, model M152-N, brand Mingmei; Low-speed centrifuge, model 2-16R, brand Hunan Hengnuo; Micropipette, model Top Pette, brand Dalong; The microplate reader, model Tecan Infinite M200, brand Tecan (Switzerland); 96-well cell culture plate, model 701002, brand NEST; MCF-10A dedicated culture medium, product number SC20201210, brand Fenghui Biotechnology; DMEM / F12 culture medium, catalog number CA1210, brand Solarbio; Fetal bovine serum, product number AUS-01S-02, brand cell-box; Pancreatic enzyme digestion solution, product number T1300, brand Solarbio; PBS buffer, catalog number G4202, brand: Xavier; CCK-8 test kit, catalog number CA1210, brand Solarbio.

[0036] 2. Experimental steps: (1) Experimental groups: control group NC (complete culture medium), blank group, galactagogue composition A experimental group, galactagogue composition B experimental group, galactagogue composition C experimental group, galactagogue composition D experimental group, galactagogue composition E experimental group, and galactagogue composition F experimental group.

[0037] (2) CCK-8 experiment Collect cells from each group separately and adjust the cell suspension concentration; take a 96-well plate, add 100 μL of cell suspension to each well, and seed the plate to make the number of cells to be tested 5 × 10⁶. 3 Cells / wells (edge ​​wells were filled with sterile PBS to eliminate edge effects), 5 replicates per group, were cultured adherently in a 5% CO2 environment at 37°C for 24 h. The blank group consisted of cell-free medium without the lactation-inducing composition, the control group cells were treated with medium without the lactation-inducing composition, and the experimental group cells were exposed to medium containing lactation-inducing compositions A-F prepared in Example 3. After the indicated 24-hour incubation period, 10 µL CCK-8 reagent was added to the corresponding well, and incubation was continued at 37°C for 1 hour. Finally, the absorbance at 450 nm was recorded, calculated using the formula: Cell viability = [(As-Ab) / (Ac-Ab)] × 100%, where As is the absorbance value of the experimental group, Ab is the absorbance value of the blank group, and Ac is the absorbance value of the control group.

[0038] 3. Experimental Results Cell viability test results as follows Figure 1 As shown in the figure. The results showed that all galactagogue compositions A to F promoted cell proliferation, with the highest cell survival rate (128.516%) in the galactagogue composition A group and the lowest (116.171%) in the galactagogue composition F group.

[0039] Experiment Example 2: Triglyceride Detection Experiment MCF-10A cells are a mammary epithelial cell line. Measuring the triglyceride content in the culture medium of MCF-10A cells can be used to study the lipid metabolism process of these cells and to evaluate the effect of the galactagogue composition on lipid synthesis. By detecting the ability of the galactagogue composition prepared in this invention to produce triglycerides in MCF-10A cells, its effect on lipids in breast milk can be indirectly reflected.

[0040] 1. Experimental materials: MCF-10A cells were provided by the School of Pharmacy, Central South University. The CO2 cell incubator, model MCO-170, is from the brand Songyang. The ultra-clean workbench, model SW-CJ-2FD-11, is from the brand Sujing Antai. Inverted microscope, model M152-N, brand Mingmei; Low-speed centrifuge, model 2-16R, brand Hunan Hengnuo; The micropipette is a Top Pette brand product. The microplate reader is a Tecan Infinite M200, a Swiss brand named Tecan. 96-well cell culture plate, model number 701002, brand name NEST; DMEM / F12 culture medium, catalog number CA1210, brand name Solarbio; Fetal bovine serum, catalog number AUS-01S-02, brand name cell-box; Pancreatic enzyme digestion solution, product number T1300, brand name Solarbio; PBS buffer, product number G4202, brand name: Xavier; Triglyceride kit, catalog number CA1210, brand name Beyotime.

[0041] 2. Experimental Grouping The experiment was divided into 8 groups: cell-free control group, blank control group NC (complete culture medium), galactagogue composition A experimental group, galactagogue composition B experimental group, galactagogue composition C experimental group, galactagogue composition D experimental group, galactagogue composition E experimental group, and galactagogue composition F experimental group.

[0042] 3. Experimental Procedure (1) Sample preparation Preparation of MCF-10A cell culture supernatant samples: After cell culture, discard the culture medium. Adherent cells are washed with PBS buffer, digested with trypsin, centrifuged, and then sonicated. The TG content in the culture medium is determined using a triglyceride (TG) kit. Specific steps can be found in the kit instructions.

[0043] (2) Determination of standards and samples Establishment of standard curve: Take 40 μL of triglyceride solution (50 mM), add 160 μL of PBS buffer and mix well to prepare a 10 mM triglyceride solution. Add 0 μL, 2.5 μL, 5 μL, 10 μL, 25 μL and 50 μL of the 10 mM triglyceride solution to the standard wells of a 96-well plate, and bring the volume to 50 μL with PBS buffer to obtain triglyceride standard solutions with concentrations of 0 mM, 0.5 mM, 1 mM, 2 mM, 5 mM and 10 mM, respectively, for establishing the standard curve.

[0044] Sample determination: Add 50 μl of the following solutions to each well of the 96-well plate according to the grouping: (1) PBS buffer was added to the cell-free control group; (2) PBS buffer was added to the blank control group; (3) The experimental groups were respectively given the corresponding galactagogue compositions A~F from Example 3; Then, add 2 μL of lipase to each well, mix well, and incubate at 37°C for 20 minutes. A sample background control well was also set up, using 2 μL of PBS buffer instead of lipase. Afterward, add 50 μL of triglyceride detection working solution to each well, mix well, and incubate at 37°C in the dark for 60 minutes. Measure the absorbance (A570). Establish a standard curve and calculate the triglyceride concentration (C) in the sample. If the signal in the sample background control well is higher, subtract the sample background control value from the sample signal value before calculation. The formula for calculating the triglyceride concentration in the sample is: C(mM) = A × 1, where A is the triglyceride concentration (mM) determined by the standard curve.

[0045] 4. Experimental Results (1) Triglyceride standard curve The absorbance results showed a good linear relationship with triglycerides in the concentration range of 0.2-10 mM, with a correlation coefficient R0. 2 The value is 0.9845, and the equation of the working curve is Y = 0.1742X + 0.1018.

[0046] (2) Effects of different lactation-inducing compositions on intracellular triglycerides in MCF-10A cells The results of triglyceride content detection in the culture medium of different experimental groups are as follows: Figure 2As shown in the figure, the results indicated that different galactagogue compositions had varying effects on triglyceride production in cells. Galactagogue composition C exhibited the strongest promoting effect on cellular lipid production, with the highest triglyceride concentration (1.932 mM). Galactagogue compositions A and B showed similar effects, with triglyceride concentrations of 1.838 mM and 1.8406 mM, respectively. Galactagogue compositions D, E, and F showed the weakest promoting effects, with triglyceride concentrations of 1.578 mM, 1.565 mM, and 1.752 mM, respectively.

[0047] Experiment Example 3: Testing the galactagogue effect of the composition through animal experiments 1. Experimental materials SPF-grade pregnant female Kunming mice, provided by Hunan Slack Jingda Experimental Animal Co., Ltd. -80℃ refrigerator, model 212990002, brand Haier; Low-speed centrifuge, model 5424R, brand eppendorf; Ultra-low temperature freezer (-86℃), model 906-ULTS, brand Thermo Fisher Scientific; Low-temperature high-speed centrifuge, model 5427 R, brand Eppendorf (Germany); Pipettes, models 2μL-1000μL, supplied by Gilson P-type pipette company; Miniature centrifuge, model TG16W, provided by Changsha Xiangzhi Centrifuge Instrument Co., Ltd. Microplate reader, model Infinite F50, brand Teco; Electric thermostatic drying oven, model GNP-9080, provided by Shanghai Jinghong Experimental Equipment Co., Ltd. Plate washer, model AC8, brand Thermo Labsystems; Bromocriptine Mesylate Tablets, brand Parlodel; Mouse prolactin (PRL) ELISA research kit, catalog number AF-3289A, provided by Aifang Biotechnology; Mouse progesterone (PROG) ELISA research kit, catalog number AF-3304A, provided by Aifang Biotechnology; Mouse estradiol (E2) ELISA research kit, catalog number AF-3302A, provided by Aifang Biotechnology.

[0048] 2. Experimental Procedure (1) Modeling and grouping of postpartum lactation-deficient female rats Animal preparation: Thirty-six SPF-grade pregnant female Kunming mice were housed in a suitable environment with free access to food and water. Mice with parturition times within 24 hours of each other were selected for the experiment, and their weight ranged from 32 ± 5.15 g. On the first day postpartum, a model group, a control group, and four experimental groups were designed, with each mother ensuring she fed eight pups.

[0049] Modeling: A postpartum hypogalactia mouse model was established by gavage administration of bromocriptine 1.6 mg / kg.

[0050] Solution preparation: Bromocriptine solution: Dissolve bromocriptine tablets (Parlodel 2.5mg / tablet) in purified water to prepare a 0.32mg / ml bromocriptine solution, and store it in a brown reagent bottle protected from light for later use. Lactation-inducing oral solution: The lactation-inducing composition A and lactation-inducing composition C obtained in Example 3 were fully dissolved in purified water to prepare an oral solution with a concentration of 15 mg / ml. The solution was stored in a brown reagent bottle away from light for later use.

[0051] Experimental Groups: This experiment included a control group, a model group, and four experimental groups. The drug administration regimens for the mother mice in each group are shown in Table 2. The control group was given pure water; the model group was given bromocriptine solution and pure water; and the experimental groups were given oral galactagogue and bromocriptine solution. The drug administration regimens are shown in Table 2.

[0052] Table 2

[0053] (2) Experimental methods 1. Measurement of milk production in female mice: During the experiment, the change in litter weight of the pups at different stages was measured daily to indirectly reflect the change in the mother's milk production. Specifically, the hourly milk production of the mother was calculated by adding the weight difference of all the pups in the litter before and after nursing for one hour to the basal metabolic rate of the entire litter within one hour.

[0054] Every morning at 10:00 AM, the mother mice are removed and gavaged, and the first weight of each litter of pups is recorded as W1, which is the litter weight before isolation. The pups are then separated from their mothers, with the pups kept warm in an incubator while the mothers have free access to food and water. Four hours after separation, at 2:00 PM, the second weight of each litter is recorded as W2, which is the litter weight before nursing. After weighing, each litter of pups is returned to its corresponding mother for one hour of free nursing. At 3:00 PM, the mother and pups are separated again, and the final weight of each litter is recorded as W3, which is the litter weight after nursing. Afterward, the mother is returned to her corresponding litter for free nursing, and the milk production is measured. The calculation formula is: milk production per hour of the mother mouse = W3-W2+(W1-W2) / 4, where W1 is the total weight of each litter of pups before isolation, W2 is the litter weight of the pups before nursing, W3 is the litter weight of the pups after nursing, and (W1-W2) / 4 is the average basal metabolic rate of each litter of pups per hour.

[0055] The pups were nursed continuously for 10 days, and the weighing process of the first day was repeated every day. The experiment ended when the litter weight was measured after the pups were nursed on the 10th day. The relevant data were then processed. Because some pups died during the experiment, abnormal data were removed, and 5 sets of data from each group were retained for processing, and the average value was taken.

[0056] 2. Monitoring of weight changes in young mice litter weight gain of baby mice = W 3x –W 1I W 3x W represents the litter weight of the pups after nursing on day 10 of the experiment. 1I The total weight of each litter of pups before isolation on day 1 of the experiment.

[0057] 3. Detection of lactation-inducing hormone indicators in female mice The levels of estradiol (E2), prolactin (PRL), and progesterone (PROG) in female mice were detected using an ELISA kit to further evaluate the effect of the lactation-inducing composition of this invention on the milk production function of lactating female mice. On day 10 of the experiment, blood was collected from the tail tip of three female mice in each group. Warm water was applied to the tail of the female mice to promote vasodilation. The tail tip was cut off by 1-2 mm, and the blood was collected. The blood was allowed to coagulate naturally at room temperature for 10-20 minutes, then centrifuged at 2000-3000 rpm for about 20 minutes. The supernatant was collected, and the levels of estradiol, prolactin, and progesterone in the female mice were measured according to the ELISA kit instructions. The average value of each group was recorded.

[0058] (III) Experimental Results 1. Changes in total milk production in lactating female mice To explore the effects of different galactagogue compositions on lactation in maternal mice, the total milk production of maternal mice during the experimental period was converted from the weight gain of pups during the specified lactation period. Milk intake was assessed by directly weighing pups to obtain the maternal milk production. The increase in total milk production of maternal mice in each group during the experimental period is shown in the table below. Figure 3 The results showed that the milk production of the mother mice administered drugs under schemes two, three, and four was higher than that of the model group, indicating that the galactagogue compositions A and C prepared in Example 3 could improve the bromocriptine-induced hypogalactia symptoms. In addition, the milk production of the mother mice in schemes three and four was higher than that in schemes one and two, indicating that the galactagogue composition C had a better galactagogue effect on hypogalactia mother mice than that of the galactagogue composition A.

[0059] 2. Effects of duration of galactagogue intake on lactation function in female rats The changes in milk production of the mother mice in each group during the experiment are as follows: Figure 4 , 5 As shown in the figure. The results indicate that the milk production of the model group mothers was consistently lower than that of the control group mothers during the experiment, demonstrating the feasibility of using bromocriptine to construct a maternal hypogalactia model.

[0060] Comparing the lactation status of the experimental group mothers with that of the model group mothers revealed the following: In Group 1, the milk production fluctuated significantly during the experimental period compared to the model group, indicating no significant improvement. In Group 2, the milk production showed some improvement compared to the model group, suggesting that the galactagogue composition A, administered at a high dose of 150 mg / kg, effectively improved the lactation symptoms in the mothers. Furthermore, the milk production in Groups 3 and 4 was significantly better than the model group from day 6 onwards, indicating that the lactation symptoms gradually improved with prolonged administration of the galactagogue composition C.

[0061] 3. Weight changes of mother mice and pups The weight gain of young mice is as follows Figure 6 As shown in the figure. The results showed that the weight gain of the control group mice was the greatest, the weight gain of the model group mice was the least, and the weight gain of the experimental group mice was higher than that of the model group.

[0062] 4. Effects of galactagogue composition intake on lactation-related hormones in female rats Depend on Figure 7 It was found that, compared with the control group, the serum estradiol (E2), prolactin (PRL), and progesterone (PROG) levels in the model group of lactation-deficient mother mice were significantly reduced, indicating that the secretion of lactation-related hormones in mother mice is significantly reduced during lactation deficiency. After administration of lactation-inducing compositions A and C, the serum levels of hormones such as E2, PRL, and PROG in mother mice increased significantly, indicating that the lactation-inducing compositions prepared in this invention have the effect of regulating lactation-related hormones.

[0063] Estradiol (E2) binds to the estrogen receptor (ER), stimulating the pituitary gland to secrete prolactin (PRL). PRL has physiological functions in regulating mammary gland development and lactation. Progesterone (PROG), the main hormone for maintaining pregnancy, can bind to PRL and promote the development of mammary alveoli and ducts. In the experimental groups, the highest E2 concentration in the first group (Scheme 1) reached 60.22 pmol / L, an increase of more than 62% compared to the model group (37.02 pmol / L). The highest PRL and PROG concentrations were observed in the fourth group (Scheme 4), with PRL reaching 69.67 pmol / L, an increase of more than 76% compared to the model group (39.42 pmol / L), PROG reaching 14.48 pmol / L, an increase of 56% compared to the model group (9.26 pmol / L), and E2 reaching 54.59 pmol / L, an increase of more than 47% compared to the model group (37.02 pmol / L). This indicates that the levels of lactation-related hormones in lactation-deficient mice were restored after administration of the lactation-inducing composition of this invention.

[0064] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A composition that helps improve postpartum hypogalactia and increase the quantity and quality of breast milk, characterized in that, It includes Angelica sinensis extract, malt extract, dandelion extract and daylily extract, wherein the mass ratio of Angelica sinensis extract, malt extract, dandelion extract and daylily extract is (0.1-0.3):(0.2-0.6):(0.01-0.03):(40-60).

2. The composition according to claim 1, characterized in that, The mass ratio of the Angelica sinensis extract, malt extract, dandelion extract and daylily extract is 0.3:0.6:0.02:

40.

3. The composition according to any one of claims 1-2, characterized in that, The Angelica sinensis extract, malt extract, dandelion extract, and daylily extract are obtained by enzymatic hydrolysis and ultrasonic treatment of Angelica sinensis, malt, dandelion, and daylily, respectively.

4. The composition according to claim 3, characterized in that, The enzymatic hydrolysis process includes: using a complex enzyme solution composed of cellulase, pectinase and papain to enzymatically hydrolyze the raw materials at a temperature of 40~50℃ and a pH of 4.5~5.

5.

5. The composition according to claim 3, characterized in that, The ultrasonic process includes: mixing the raw material with the extraction solvent, ultrasonically extracting at an ultrasonic frequency of 20-30 kHz for 20-70 minutes, and controlling the ultrasonic temperature at 30-50℃.

6. The composition according to any one of claims 1-2, characterized in that, The Angelica sinensis extract, malt extract, dandelion extract, and daylily extract were prepared by the following method: S1. Angelica sinensis, malt, dandelion, and daylily raw materials are dried and pulverized to obtain raw material powder; S2. The raw material powder is mixed with the compound enzyme solution for enzymatic hydrolysis. The mass ratio of cellulase, pectinase and papain in the compound enzyme solution is 1:1:0.

5. The enzymatic hydrolysis temperature is 40~50℃, the enzymatic hydrolysis pH is 4.5~5.5, and the enzymatic hydrolysis time is 30~40min to obtain the enzymatically hydrolyzed raw material. S3. The enzymatically hydrolyzed raw material is mixed with the first extraction solvent and subjected to ultrasonic extraction. The ultrasonic frequency is 20~30kHz, the ultrasonic temperature is controlled at 30~50℃, and the ultrasonic time is 30~40 minutes. After ultrasonic extraction, the mixture is filtered to separate the first extract and the raw material residue. S4. Add a second extraction solvent to the raw material residue and mix for ultrasonic extraction. The volume of the second extraction solvent is 50-70% of the volume of the first extraction solvent. The ultrasonic frequency is 20-30 kHz, the ultrasonic temperature is controlled at 30-50°C, and the ultrasonic time is 20-30 minutes. After filtration, a second extract is obtained. The second extract is combined with the first extract to obtain the raw material extract. S5. The raw material extract is concentrated and dried to obtain the Angelica sinensis extract, malt extract, dandelion extract and daylily extract.

7. The composition according to claim 6, characterized in that, Both the first and second extraction solvents are ethanol solutions.

8. The composition according to claim 6, characterized in that, The composition further includes excipients or additives that can be used in food or pharmaceuticals, wherein the excipients or additives are at least one of coating agents, sweeteners, antioxidants, thickeners, anti-caking agents and emulsifiers.

9. An application of the composition according to any one of claims 1-8, characterized in that, The invention includes at least one of the following: oral formulations made from the composition for improving postpartum hypogalactia, increasing milk production, and improving milk quality.

10. The application as described in claim 9, characterized in that, The oral preparation is one of the following: powder, granules, capsules, tablets, oral solution, or emulsion.

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