Corn for preventing or improving climacteric comprehensive symptoms and planting method and application thereof

By mixing pregnant horse urine with macroporous resin and adsorbing estrogen, and using fermented pregnant horse urine and horse manure compound fertilizer to plant corn, the poor efficacy and environmental pollution of the treatment of menopause syndrome in the existing technology have been solved, and the improvement of sex hormone levels and the relief of menopause symptoms have been achieved. At the same time, it has efficient comprehensive resource utilization and green environmental protection advantages.

CN119817740APending Publication Date: 2025-04-15TEFENG PHARM CO LTD +2
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Patent Information

Application Number
CN202411553344.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2024-09-05
Filing Date
2024-11-01
Publication Date
2025-04-15

AI Technical Summary

Technical Problem

The prior art has problems such as poor efficacy, obvious side effects and environmental pollution in preventing or improving menopause syndrome. Especially in the treatment of pregnant horse urine and horse manure, there are complex extraction, separation and purification processes and three waste treatments.

Method used

By mixing pregnant horse urine with macroporous resin and adsorbing estrogen, combined with fermented pregnant horse urine and horse manure compound fertilizers for planting corn, the bioconversion function of corn is used to realize the efficient recycling and utilization of the adsorption effluent of pregnant horse urine resin and the sex hormones and nutrients contained in horse manure, corn of casserosterol, stigmasterol and β-sitosterol were prepared.

Benefits of technology

Significantly improve sex hormone levels, thicken vaginal mucosa, reduce pathological scores, relieve menopause anxiety and depression, improve osteoporosis, and the yield of corn and corn stalks grown is high, tastes good, easy to use, high bioavailability, safe and effective, high comprehensive resource utilization rate, and green and environmentally friendly.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

The invention relates to corn for preventing or improving climacteric comprehensive symptoms, which is characterized in that efficient comprehensive utilization of sex hormones and nutritional ingredients contained in pregnant mare urine resin adsorption effluent and horse manure is realized by utilizing biotransformation of the corn, efficient recycling of three wastes is promoted, and the treatment cost of the three wastes is remarkably reduced; environmental pollution is remarkably reduced, the comprehensive utilization rate of pregnant horse farm or pregnant horse base resources and three wastes is remarkably increased, and the method has the advantages of being easy and convenient to operate, high in resource comprehensive utilization rate, environmentally friendly, higher in cost, suitable for industrial production and the like.
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Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to corn for preventing or improving menopausal syndrome, a planting method thereof and an application thereof. Background Art

[0002] Typical symptoms of menopausal syndrome (also known as perimenopausal syndrome) include menstrual changes (including shortened, irregular, and sudden cessation of periods), vasomotor symptoms (including hot flashes, which may be accompanied by sweating, headaches, palpitations, etc.), and neuropsychiatric symptoms (including mood swings, inattention, memory loss, and sleep disorders). Accompanying symptoms of menopausal syndrome include atrophic changes in the urogenital system, decreased bone mass and osteoporosis, decreased sex hormone levels and decreased sexual function, and muscle aches. Menopausal syndrome seriously affects the health and quality of life of patients. Effective measures need to be taken to prevent or improve menopausal syndrome symptoms and delay the onset of menopause in order to significantly improve the health and quality of life of patients.

[0003] Menopausal syndrome is prone to abnormal emotions due to changes in hormone levels and the resulting changes in body functions. In severe cases, people may even experience anxiety and depression, accompanied by insomnia, palpitations, backaches and other discomforts. Sex hormone drugs can be supplemented under the guidance of a doctor to relieve and improve the uncomfortable symptoms of menopause. The treatment drugs for menopausal syndrome include Fenmaten, Anjinyi, Tibolone, Climen, Progynova, Dydrogesterone Tablets, Asterol Gel, Gengbaofen, Ovitin, Kuntai Capsules, Lifumin, Jinfeng Pills, etc., and sour jujube seeds, lilies, lotus seeds, evening primrose oil soft capsules, etc. are used to regulate endocrine. However, there are defects such as poor efficacy, nausea, headaches, irregular vaginal bleeding, and breast pain.

[0004] Symptoms of menopausal osteoporosis include pain and bone pain, fatigue and deformity caused by decreased bone density (including spinal compression and deformation, forward leaning and back curvature, resulting in vertebral deformation and shortened height, stooping, hunchback, etc.). After suffering from slight external injuries, patients are prone to pathological fractures in the lumbar spine, wrist joints and other parts, and have discomfort symptoms such as decreased respiratory function. Osteoporosis treatment drugs include calcium gluconate oral solution, vitamin D3 capsules, calcium carbonate D3 granules, sodium alendronate enteric-coated tablets, sodium risedronate tablets, glucosamine sulfate capsules, glucosamine hydrochloride tablets, calcium magnesium zinc copper vitamin D tablets, etc. However, there are defects such as poor absorption and gastrointestinal discomfort.

[0005] Treatments for depression and anxiety include lifestyle adjustments, exercise therapy, a healthy diet, social support, psychotherapy, and medication. Drugs for depression and anxiety include lorazepam, estazolam, alprazolam, paroxetine, sertraline, venlafaxine, duloxetine, escitalopram, diazepam tablets, fluoxetine, and others.

[0006] Conjugated Equine Estrogens (CEE) is a natural mixed estrogen extracted from pregnant mare urine. It has the effects of preventing and treating estrogen deficiency caused by physiological and pathological reasons, activating body functions, and delaying aging. It is clinically used for ovarian insufficiency, uterine hypoplasia, functional uterine bleeding, menopausal syndrome, senile vaginitis, prostate cancer, as well as for nosebleeds, gynecological bleeding, and bleeding during surgery.

[0007] CN103720720A discloses a method for extracting, separating and purifying conjugated estrogen from pregnant mare urine. The method collects pregnant mare urine and applies macroporous resin to absorb and extract about 80% of the conjugated estrogen in pregnant mare urine. The pregnant mare urine effluent after resin adsorption needs to be recycled or treated as three wastes. In order to prevent environmental pollution, if the pregnant mare urine effluent after resin adsorption and the conjugated estrogen contained therein need to be recycled, a complex extraction, separation and purification process is required, and the three wastes generated thereby need to be discharged after being treated according to the three wastes treatment requirements, and there are problems such as a long treatment cycle of the pregnant mare urine effluent, a large amount of three wastes, and high cost.

[0008] Lan Tian et al. (Study on the preservation time of steroid hormone levels in Przewalski's horse feces, Section 4 of Beijing Forestry University Master's Thesis) found that pregnant horse feces contain testosterone (about 80ng / ml), progesterone (about 2380ng / ml), estradiol (about 4480pg / ml) and other sex hormones. If the sex hormones contained in pregnant horse feces need to be recycled, complex extraction, separation and purification processes are also required, and the three wastes generated need to be treated in accordance with the three wastes treatment requirements before being discharged. There are also problems such as long pregnant horse feces treatment cycle, large amount of three wastes, and high cost.

[0009] Corn is rich in nutrients such as carbohydrates, proteins, dietary fiber, vitamins (such as B vitamins, vitamin E, vitamin A, etc.) and minerals (such as calcium, potassium, zinc, manganese, etc.), and there are a variety of corn products (such as fresh corn, corn kernels, corn grits, corn flour, cornmeal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husk residue, corn syrup, corn flakes, corn wine, corn popcorn, corn feed, etc.) to meet the public's consumption and / or use needs, and are used to supplement the nutrients, energy and protein required by the body, improve gastrointestinal motility, protect skin cells and delay skin aging, promote blood circulation, relieve stress and anxiety, etc. For this reason, how to efficiently utilize the sex hormones and nutritional components contained in pregnant mare urine and horse manure, and the biotransformation function of corn have become research hotspots in this field. Summary of the invention

[0010] The object of the present invention is to provide a corn for preventing or improving menopausal syndrome, wherein the mass ratio of campesterol:stigmasterol:β-sitosterol in the corn is 1:0.5-5:1-5.

[0011] In the preferred technical solution of the present invention, the campesterol in the corn: stigmasterol:

[0012] The mass ratio of β-sitosterol is 1:0.6-2:1-4.

[0013] In the preferred technical solution of the present invention, the campesterol in the corn: stigmasterol:

[0014] The mass ratio of β-sitosterol is selected from any one of 20.3:23.0:55.7, 30.5:31.7:51.4, and 28.3:21.2:110.6.

[0015] In the preferred technical solution of the present invention, the corn planting method comprises the following steps:

[0016] (1) Collect urine and feces from pregnant horses separately;

[0017] (2) uniformly mixing the collected pregnant mare urine with a macroporous resin and applying the mixture to a column, using the macroporous resin to adsorb the conjugated estrogen in the pregnant mare urine, and then mixing the collected pregnant mare urine resin adsorption effluent with horse manure in a mass ratio of 1:5-1:15, and fermenting the mixture for 2-4 months to obtain a pregnant mare urine and horse manure composite fertilizer;

[0018] (3) After fertilizing the soil to be sown with 2-3 tons of pregnant horse urine and horse manure compound fertilizer per mu of land, the soil is plowed, corn is sown, and the mature corn is harvested.

[0019] In the preferred technical solution of the present invention, the pregnant mare urine and the macroporous resin are mixed in a volume ratio of 4:1-1:1, preferably 2:1-3:1.

[0020] In a preferred technical solution of the present invention, the macroporous resin is a styrene-divinylbenzene medium-polar macroporous resin having an ester structure.

[0021] In the preferred technical solution of the present invention, the flow rate of the pregnant mare urine macroporous resin mixed solution on the column is 1-4 volumes of horse urine / h, preferably 2-3 volumes of horse urine / h.

[0022] In a preferred technical solution of the present invention, the fermentation is anaerobic fermentation.

[0023] In the preferred technical scheme of the present invention, the mass ratio of the pregnant mare urine resin adsorption effluent to the horse manure in the preparation of the pregnant mare urine and horse manure composite fertilizer is 1:6-1:12, preferably 1:8-1:10.

[0024] In the preferred technical solution of the present invention, the plant spacing of corn is 18-20 cm, and the row spacing is 45-50 cm.

[0025] In the preferred technical solution of the present invention, no fertilizer is applied during corn planting.

[0026] Another object of the present invention is to provide a method for planting corn for preventing or improving menopausal syndrome, wherein the mass ratio of campesterol:stigmasterol:β-sitosterol in the corn is 1:0.5-5:1-5, and the method comprises the following steps:

[0027] (1) Collect urine and feces from pregnant horses separately;

[0028] (2) uniformly mixing the collected pregnant mare urine with a macroporous resin and applying the mixture to a column, using the macroporous resin to adsorb the conjugated estrogen in the pregnant mare urine, and then mixing the collected pregnant mare urine resin adsorption effluent with horse manure in a mass ratio of 1:5-1:15, and fermenting the mixture for 2-4 months to obtain a pregnant mare urine and horse manure composite fertilizer;

[0029] (3) After fertilizing the soil to be sown with 2-3 tons of pregnant horse urine and horse manure compound fertilizer per mu of land, the soil is plowed, corn is sown, and the mature corn is harvested.

[0030] In the preferred technical solution of the present invention, the pregnant mare urine and the macroporous resin are mixed in a volume ratio of 4:1-1:1, preferably 2:1-3:1.

[0031] In a preferred technical solution of the present invention, the macroporous resin is a styrene-divinylbenzene medium-polar macroporous resin having an ester structure.

[0032] In the preferred technical solution of the present invention, the flow rate of the pregnant mare urine macroporous resin mixed solution on the column is 1-4 volumes of horse urine / h, preferably 2-3 volumes of horse urine / h.

[0033] In a preferred technical solution of the present invention, the fermentation is anaerobic fermentation.

[0034] In the preferred technical solution of the present invention, the mass ratio of horse urine to horse manure in preparing the composite fertilizer of pregnant horse urine and horse manure is 1:6-1:12, preferably 1:8-1:10.

[0035] In the preferred technical solution of the present invention, the plant spacing of corn is 18-20 cm, and the row spacing is 45-50 cm.

[0036] In the preferred technical solution of the present invention, no fertilizer is applied during corn planting.

[0037] In the preferred technical solution of the present invention, the campesterol in the corn: stigmasterol:

[0038] The mass ratio of β-sitosterol is 1:0.6-2:1-4.

[0039] In the preferred technical solution of the present invention, the campesterol in the corn: stigmasterol:

[0040] The mass ratio of β-sitosterol is selected from any one of 20.3:23.0:55.7, 30.5:31.7:51.4, and 28.3:21.2:110.6.

[0041] Another object of the present invention is to provide a corn product for preventing or improving menopausal symptoms made from the corn of the present invention, wherein the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husks, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

[0042] Another object of the present invention is to provide the use of the corn of the present invention in preparing products for preventing and / or improving menopausal syndrome in patients.

[0043] In the preferred technical scheme of the present invention, the menopausal symptoms are selected from any one or a combination of menopausal weight loss, menopausal obesity, ovarian dysfunction, sex hormone imbalance, thinning of vaginal mucosa, decreased endometrial thickness, abnormal non-menstrual bleeding, hot flashes, hyperhidrosis, insomnia, mood swings, vaginal dryness, osteoporosis, anxiety, and depression.

[0044] In the preferred technical scheme of the present invention, the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husk residue, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

[0045] Another object of the present invention is to provide a pharmaceutical composition for preventing or improving menopausal syndrome, wherein the composition is composed of a drug for preventing and / or treating menopausal syndrome and the corn of the present invention.

[0046] In the preferred technical scheme of the present invention, the drug for preventing and / or treating menopausal syndrome is selected from any one or a combination of Fenmaten, Anjinyi, Tibolone, Climen, Progynova, Dydrogesterone Tablets, Asterol Gel, Gengbaofen, Oveting, Kuntai Capsules, Lifumin, Jinfeng Pills, Ziziphus jujuba seeds, lily, lotus seeds, and evening primrose oil soft capsules.

[0047] Another object of the present invention is to provide a use of the corn of the present invention in preparing a product for improving sex hormone levels.

[0048] In the preferred technical solution of the present invention, the improved sex hormone level is selected from the group consisting of improving estradiol level, testosterone level, progesterone level, β-endorphin level, follicle stimulating hormone level,

[0049] (FSH) level, luteinizing hormone level, or any one or a combination thereof.

[0050] In the preferred technical scheme of the present invention, the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husk residue, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

[0051] Another object of the present invention is to provide a pharmaceutical composition, which is composed of a drug for preventing and / or treating menopausal syndrome and the corn of the present invention.

[0052] In the preferred technical scheme of the present invention, the drug for preventing and / or treating menopausal syndrome is selected from any one or a combination of Fenmaten, Anjinyi, Tibolone, Climen, Progynova, Dydrogesterone Tablets, Asterol Gel, Gengbaofen, Oveting, Kuntai Capsules, Lifumin, Jinfeng Pills, Ziziphus jujuba seeds, lily, lotus seeds, and evening primrose oil soft capsules.

[0053] Another object of the present invention is to provide an application of the corn of the present invention in preparing a product for bidirectionally regulating anxiety and depression symptoms.

[0054] In the preferred technical scheme of the present invention, the anxiety and depression symptoms are selected from any one of anxiety, sadness, helplessness, fear, reduced self-worth and happiness, tension, depression, upset, unhappiness, distraction, unclear thinking, insomnia, loss of appetite, fatigue, gastrointestinal dysfunction, pain, and menopausal anxiety and depression.

[0055] In the preferred technical scheme of the present invention, the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husk residue, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

[0056] Another object of the present invention is to provide a pharmaceutical composition for bidirectionally regulating anxiety and depression symptoms, wherein the composition is composed of an anti-anxiety and depression drug and the corn of the present invention.

[0057] In the preferred technical scheme of the present invention, the antianxiety and depression drug is selected from any one of lorazepam, estazolam, alprazolam, paroxetine, sertraline, venlafaxine, duloxetine, escitalopram, diazepam tablets, fluoxetine or a combination thereof.

[0058] Another object of the present invention is to provide an application of the corn of the present invention in preparing a product for preventing or improving osteoporosis symptoms.

[0059] In a preferred technical solution of the present invention, the osteoporosis is selected from any one of menopausal osteoporosis and rickets, or a combination thereof.

[0060] In the preferred technical scheme of the present invention, the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husk residue, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

[0061] Another object of the present invention is to provide a pharmaceutical composition having the efficacy of preventing or improving the symptoms of osteoporosis, wherein the composition is composed of a drug for treating osteoporosis and the corn of the present invention.

[0062] In the preferred technical scheme of the present invention, the drug for treating osteoporosis is selected from any one of calcium gluconate oral solution, vitamin D3 capsules, calcium carbonate D3 granules, alendronate sodium enteric-coated tablets, risedronate sodium tablets, glucosamine sulfate capsules, glucosamine hydrochloride tablets, and calcium magnesium zinc copper vitamin D tablets or a combination thereof.

[0063] The present invention adopts the following high performance liquid chromatography method to detect the content of campesterol, stigmasterol and β-sitosterol contained in corn:

[0064]

[0065]

[0066] Unless otherwise specified, the present invention uses the following high performance liquid chromatography method to detect the content of campesterol, stigmasterol and β-sitosterol contained in corn:

[0067] (1) Accurately weigh 30 mg of stigmasterol, 30 mg of β-sitosterol and 15 mg of campesterol standard respectively, place them in a 10 mL volumetric flask, add methanol to dissolve and dilute to volume to prepare a mixed standard stock solution. Accurately pipette 133 μL of the mixed standard stock solution, blow the methanol dry with a nitrogen blower, dissolve it in acetonitrile, transfer it to a 10.0 mL volumetric flask, dilute to the scale with acetonitrile, and prepare a mixed standard solution of 40 μg / mL stigmasterol, 40 μg / mL β-sitosterol and 20 μg / mL campesterol. Store it in a brown volumetric flask at 4°C for future use.

[0068] (2) Use a wall crusher to squeeze the corn to be tested into a paste. Accurately weigh 30 g of corn paste, place it in a conical flask, add 300 ml of anhydrous ethanol, stir evenly, and place it under 35°C for ultrasonic extraction for 50 minutes; collect the supernatant, filter it with a 0.22 μm membrane, and prepare the test solution.

[0069] (3) Take 1 ml of the test solution, place it at 40°C and blow it dry with nitrogen, then add 0.5 ml of the mixed standard solution and 0.5 ml of methanol, and dissolve it by ultrasonication to prepare the spiked test solution.

[0070] (4) Take the test sample solution and the spiked test sample solution, and test them according to the HPLC detection conditions described in Table 1, and calculate the peak area and content of campesterol, stigmasterol and β-sitosterol in corn.

[0071] Table 1

[0072]

[0073] Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentage is volume / volume percentage; when the present invention relates to the percentage between liquids and solids, the percentage is volume / weight percentage; when the present invention relates to the percentage between solids and liquids, the percentage is weight / volume percentage; the rest are weight / weight percentages.

[0074] Compared with the prior art, the present invention has the following beneficial technical effects:

[0075] 1. The present invention utilizes macroporous resin to adsorb conjugated estrogens in pregnant mare urine, and then mixes the collected pregnant mare urine resin adsorption effluent and horse manure in a mass ratio of 1:5-1:15. The pregnant mare urine and horse manure composite fertilizer obtained by fermentation is used for planting corn, and the biotransformation of corn is utilized to realize efficient recovery and utilization of sex hormones and nutrients contained in the pregnant mare urine resin adsorption effluent and horse manure. The mass ratio of campesterol:stigmasterol:β-sitosterol in the obtained planted corn is 1:0.5-5:1-5.

[0076] 2. The present invention comprehensively utilizes pregnant horse urine, pregnant horse urine resin adsorption effluent and horse manure produced by pregnant horse farms or pregnant horse bases, and ferments the pregnant horse urine and horse manure compound fertilizers to plant corn. Preliminary animal experiments have shown that the planting corn of the present invention can significantly improve sex hormone levels, thicken vaginal mucosa, significantly reduce pathological scores, effectively relieve menopausal anxiety and depression in patients, improve menopausal osteoporosis, can be used to prevent or improve menopausal syndrome, and has the advantages of high yield of planting corn and corn stalks, good taste, easy use, high bioavailability, safety and effectiveness, high comprehensive resource utilization rate, and green environmental protection.

[0077] 3. The present invention utilizes the biotransformation of corn to achieve efficient and comprehensive utilization of the sex hormones and nutrients contained in the pregnant mare urine resin adsorption effluent and horse manure, and promotes the efficient recycling of the three wastes, significantly reduces the cost of the three wastes treatment, significantly reduces environmental pollution, and significantly improves the comprehensive utilization rate of the resources and three wastes of the pregnant mare farm or pregnant mare base. It has the advantages of simple operation, high comprehensive utilization of resources, green environmental protection, better cost, and suitability for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Figure 1 Effect of planting corn on body weight of menopausal model rats;

[0079] Figure 2 The effect of planting corn on the sex hormone level of menopausal model rats;

[0080] Figure 3 Effect of corn planting on uterine pathology in menopausal model rats (HEX100)

[0081] Figure 4 Effect of corn planting on vaginal pathology in menopausal rat model (HEX100)

[0082] Figure 5 Research on the effect of planting corn on improving anxiety symptoms in menopausal model rats;

[0083] Figure 6 Study on the effect of planting corn in the present invention on improving depression symptoms in menopausal model rats;

[0084] Figure 7 The present invention studies the effect of planting corn on femoral bone density in menopausal model rats. DETAILED DESCRIPTION

[0085] The above contents of the present invention are further described in detail below through specific implementation methods, but this should not be understood as any limitation to the subject matter of the present invention. All technical solutions implemented based on the above contents of the present invention belong to the scope of the present invention.

[0086] In a specific embodiment, GB / T 6432-2018 7.1 is used to detect crude protein in horse manure, GB / T 6433-2006A is used to detect crude fat in horse manure, and GB / T

[0087] 6434-2022 6》Detection of crude fiber in horse manure, 《GB / T 6436-2018 4》Detection of calcium in horse manure, 《NY / T1459-2022》Detection of acid detergent fiber in horse manure,

[0088] "GB / T 20806-2022 4" detects neutral detergent fiber (NDF) in horse manure, and "GB5009.3-2016 Method 1" detects moisture in horse manure.

[0090] In a specific embodiment, the test results of horse manure are: crude protein 30.93%, crude fat 18%, neutral detergent fiber 17.1%, acid detergent fiber 9.3%, crude fiber 8.9%.

[0091] and calcium 0.097%.

[0092] In a specific embodiment, the waxy corn is Sukenuo 1801 (approval number: Guoshenyu 20210132), and the field corn is Shangyu 288. Animal feed was purchased from Tianjin Keao Xieli Feed Co., Ltd.

[0093] Example 1 Planting of corn of the present invention

[0094] The corn planting method of the present invention comprises the following steps:

[0095] (1) Selecting Kazakh native pregnant horses and collecting horse urine and horse feces from them;

[0096] (2) mixing the collected pregnant mare urine with a styrene-divinylbenzene medium polar macroporous resin having an ester structure in a volume ratio of 2:1, applying the mixture to a column at a flow rate of 2 volumes of mare urine / h, and collecting the mare urine resin adsorption effluent;

[0097] (3) mixing the collected pregnant mare urine resin adsorption effluent and horse manure in a mass ratio of 1:8, and fermenting for 2.5 months to obtain a pregnant mare urine and horse manure composite fertilizer;

[0098] (4) After applying the prepared compound fertilizer of pregnant horse urine and horse manure to the soil to be sown at a rate of 2-3 tons / mu, the soil is ploughed and Sukenuo 1801 glutinous corn is sown with a plant spacing of 18 cm and a row spacing of 45 cm. The corn is harvested after maturity.

[0099] According to the method of the present invention, the mass ratio of campesterol:stigmasterol:β-sitosterol in the planted corn is 20.3:23.0:55.7.

[0100] Example 2 Planting of corn of the present invention

[0101] The corn planting method of the present invention comprises the following steps:

[0102] (1) Selecting Kazakh native pregnant horses and collecting horse urine and horse feces from them;

[0103] (2) mixing the collected pregnant mare urine with a styrene-divinylbenzene medium polar macroporous resin having an ester structure in a volume ratio of 2:1, applying the mixture to a column at a flow rate of 2 volumes of mare urine / h, and collecting the mare urine resin adsorption effluent;

[0104] (3) uniformly mixing the collected pregnant mare urine resin adsorption effluent and horse manure in a mass ratio of 1:6, and fermenting for 3 months to obtain a pregnant mare urine and horse manure composite fertilizer;

[0105] (4) After applying the prepared compound fertilizer of pregnant horse urine and horse manure to the soil to be sown at a rate of 2-3 tons / mu, the soil is ploughed and Sukenuo 1801 glutinous corn is sown with a plant spacing of 18 cm and a row spacing of 45 cm. The corn is harvested after maturity.

[0106] According to the method of the present invention, the mass ratio of campesterol:stigmasterol:β-sitosterol in the planted corn is 30.5:31.7:51.4.

[0107] Example 3 Planting of corn of the present invention

[0108] The corn planting method of the present invention comprises the following steps:

[0109] (1) Selecting Kazakh native pregnant horses and collecting horse urine and horse feces from them;

[0110] (2) mixing the collected pregnant mare urine with a styrene-divinylbenzene medium polar macroporous resin having an ester structure in a volume ratio of 2:1, applying the mixture to a column at a flow rate of 2 volumes of horse urine / h, and collecting the pregnant mare urine resin adsorption effluent;

[0111] (3) mixing the collected pregnant mare urine resin adsorption effluent and horse manure in a mass ratio of 1:10, and fermenting for 2 months to obtain a pregnant mare urine and horse manure composite fertilizer;

[0112] (4) Apply the prepared compound fertilizer of pregnant horse urine and horse manure to the soil to be sown at a rate of 2-3 tons per mu, plow the soil, sow field corn (Shangyu 288) with a plant spacing of 18 cm and a row spacing of 45 cm, and harvest the mature corn.

[0113] According to the method of the present invention, the mass ratio of campesterol:stigmasterol:β-sitosterol in the planted corn is 28.3:21.2:110.6.

[0114] Test Example 1 Study on the effect of corn of the present invention on the body weight of menopausal model rats

[0115] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were anesthetized with isoflurane and bilateral ovariectomy was performed, and the sham operation group only removed the fat near the ovaries, and the ovaries were not removed. The experimental grouping, feeding feed, dosage, frequency of administration and administration method are shown in Table 2.

[0116] Table 2

[0117]

[0118]

[0119] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks, and the weight of the experimental rats was measured every week. After bilateral ovarian castration, the experimental rats had estrogen disorders and endocrine disorders, and their overall weight increased significantly. The experimental results are shown in Figure 1 .

[0120] The experimental data were statistically analyzed using SPSS23.0, and the normality and homogeneity of variance were tested using Leven's test.

[0121] After 8 weeks of feeding, the body weight of rats in the model group increased significantly compared with that in the sham operation group ( + P≤0.05). Compared with the model group, there was no significant difference in body weight between the positive control group and experimental groups 1 to 3.

[0122] Test Example 2 Study on the effect of corn of the present invention on improving the sex hormone level of menopausal model rats

[0123] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were subjected to bilateral ovariectomy after isoflurane anesthesia, and the sham operation group was subjected to isoflurane anesthesia after only the fat near the ovary was removed, and the ovaries were not removed. The experimental grouping, feeding feed, dosage, frequency of administration and administration method were the same as Table 2 of Test Example 1.

[0124] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks. 24 hours after the last medication or feeding, blood was collected from the abdominal aorta of the experimental rats after anesthesia, and the Elisa kit was used to detect the levels of estradiol (E2), β-endorphin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum of the experimental rats.

[0125] The experimental data were statistically analyzed using SPSS23.0, and Leven's test was used to test normality and homogeneity of variance. After feeding for 8 weeks, the effects of corn cultivation on the serum sex hormone E2 level, FSH level, LH level and β-endorphin level of the experimental rats were shown in Figure 2 A-2D.

[0126] After 8 weeks of feeding, the estradiol (E2) level in the model group was significantly higher than that in the sham operation group.

[0127] There were significant differences in the levels of β-endorphin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the sham operation group (compared with the sham operation group, ++ P≤0.01). Compared with the model group, the levels of estradiol and β-endorphin in groups 1 to 3 were significantly increased and comparable to those in the positive control group. The levels of FSH and LH in groups 1 to 3 were comparable to or better than those in the positive control group (compared with the model group, * P≤0.05, ** P≤0.01; compared with the positive control group, ## P≤0.01).

[0128] Test Example 3 Study on the effect of corn of the present invention on improving uterine and vaginal tissue pathology in menopausal model rats

[0129] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were subjected to bilateral ovariectomy after isoflurane anesthesia, and the sham operation group was subjected to isoflurane anesthesia after only the fat near the ovary was removed, and the ovaries were not removed. The experimental grouping, feeding feed, dosage, frequency of administration and administration method were the same as Table 2 of Test Example 1.

[0130] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks. 24 hours after the last medication or feeding, the experimental rats were anesthetized and their uterus and vagina were removed for histopathological examination. Figure 3-4 .

[0131] There were no abnormalities in the vaginal mucosa and endometrium of the rats in the sham operation group. Compared with the sham operation group, the vaginal mucosa of the rats in the model group became thinner and the thickness of the endometrium decreased. Compared with the model group, the effects of improving the thickness of the vaginal mucosa and endometrium in groups 1 to 3 and the positive control group were basically the same.

[0132] Test Example 4 Study on the effect of planting corn in the present invention on improving anxiety symptoms in menopausal model rats

[0133] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were subjected to bilateral ovariectomy after isoflurane anesthesia, and the sham operation group was subjected to isoflurane anesthesia after only the fat near the ovary was removed, and the ovaries were not removed. The experimental grouping, feeding feed, dosage, frequency of administration and administration method were the same as Table 2 of Test Example 1.

[0134] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks. 24 hours after the last medication or feeding, the experimental rats were subjected to the open field test. The experimental rats were placed in the activity box and adapted to the environment for 3 minutes. The JL Behv animal behavior video analysis system was used to record the autonomous activities of the experimental rats within 10 minutes. After each test, the animal activity box was cleaned and the next batch of animals were tested.

[0135] The experimental data were statistically analyzed using SPSS23.0, and Leven's test was used to test normality and homogeneity of variance. After 8 weeks of feeding, the results of the improvement effect of corn planted in the present invention on anxiety and depression symptoms in menopausal model rats are shown in Figure 5 A-5D.

[0136] Compared with the sham operation group, the total distance, average speed, and central area activity time of the rats in the model group were significantly reduced, and the number of activities was significantly increased (compared with the sham operation group, ++ P≤0.01), the experimental animals showed anxiety.

[0137] Compared with the model group, the total distance, average speed, and central area activity time of rats in groups 1 to 3 were significantly increased, and the number of activities was significantly reduced, which was comparable to that of the positive control group (compared with the model group, * P≤0.05, ** P≤0.01; compared with the positive control group,

[0138] ## P≤0.01; compared with test 1 group, △P≤0.05).

[0139] Test Example 5 Study on the effect of planting corn in the present invention on improving depression symptoms in menopausal model rats

[0140] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were subjected to bilateral ovariectomy after isoflurane anesthesia, and the sham operation group was subjected to isoflurane anesthesia after only the fat near the ovary was removed, and the ovaries were not removed. The experimental grouping, feeding feed, dosage, frequency of administration and administration method were the same as Table 2 of Test Example 1.

[0141] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks. 24 hours after the last medication or feeding, the experimental rats were anesthetized and their brain tissues were taken to detect their 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels.

[0142] The experimental data were statistically analyzed using SPSS23.0, and Leven's test was used to test normality and variance homogeneity. After feeding for 8 weeks, the effects of corn cultivation on the 5-HT level and NE level in the brain tissue of menopausal model rats were shown in Figure 6 .

[0143] Compared with the sham operation group, the 5-HT in the brain tissue of the rats in the model group was significantly increased, and the NE was significantly decreased (compared with the sham operation group, * P≤0.05, ** P≤0.01). Compared with the model group, 5-HT in test groups 1-3 and the positive control group was significantly decreased, and NE was significantly increased (compared with the model group, * P≤0.05,* * P≤0.01), bidirectionally regulating anxiety and depression in menopausal rats.

[0144] Test Example 6 Study on the effect of corn of the present invention on femoral bone density in menopausal model rats

[0145] 36 female SD rats of SPF grade and body weight of 255.0-380.3g were selected and randomly divided into six groups according to body weight: sham operation group, model group, positive control group (vaginal administration of estradiol gel, Jiangxi Renhu Biotechnology Co., Ltd.), test group 1 to test group 3 (planted corn of Example 1-3), 6 rats in each group, wherein the model group, positive control group, test group 1 to group 3 were anesthetized with isoflurane and bilateral ovariectomy was performed, and the sham operation group only removed the fat near the ovaries, and did not remove the ovaries. The experimental grouping, feeding feed, dosage, frequency of administration and administration method were the same as Table 2 of Experimental Example 1.

[0146] Four weeks after surgery, the experimental animals were continuously medicated and fed for 8 weeks. 24 hours after the last medication or feeding, the femur of the experimental rats was taken after anesthesia to test the bone density. The experimental data were statistically analyzed using SPSS 23.0, and the Leven's test method was used to test normality and homogeneity of variance. After 8 weeks of feeding, the effect of planting corn on the femoral bone density of menopausal model rats is shown in Figure 7 .

[0147] Compared with the sham operation group, the femoral bone density of rats in the model group was significantly decreased (compared with the sham operation group, ++ P≤0.01). Compared with the model group, experimental groups 1 to 3 and the positive control group could significantly increase the femoral bone density of rats (compared with the model group, * P≤0.05, ** P≤0.01; compared with the positive control group, ## P≤0.01).

[0148] The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art may make various changes or modifications based on the present invention. As long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims

1. A corn for preventing or improving menopausal syndrome, wherein the mass ratio of campesterol:stigmasterol:β-sitosterol in the corn is 1:0.5-5:1-5.

2. The corn according to claim 1, wherein the mass ratio of campesterol:stigmasterol:β-sitosterol in the corn is 1:0.6-2:1-4.

3. The method for planting corn for preventing or improving menopausal syndrome according to any one of claims 1 to 2, wherein the mass ratio of campesterol:stigmasterol:β-sitosterol in the corn is 1:0.5-5:1-5, comprising the following steps: (1) Collect urine and feces from pregnant horses separately; (2) uniformly mixing the collected pregnant mare urine with a macroporous resin and applying the mixture to a column, using the macroporous resin to adsorb the conjugated estrogen in the pregnant mare urine, and then mixing the collected pregnant mare urine resin adsorption effluent with horse manure in a mass ratio of 1:5-1:15, and fermenting the mixture for 2-4 months to obtain a pregnant mare urine and horse manure composite fertilizer; (3) After fertilizing the soil to be sown with 2-3 tons of pregnant horse urine and horse manure compound fertilizer per mu of land, the soil is plowed, corn is sown, and the mature corn is harvested.

4. The planting method as claimed in claim 3, wherein the pregnant mare urine and the macroporous resin are mixed in a volume ratio of 4:1-1:1, preferably 2:1-3:

1.

5. The planting method according to any one of claims 3 to 4, wherein the macroporous resin is a styrene-divinylbenzene medium-polar macroporous resin having an ester structure.

6. The planting method according to any one of claims 3 to 5, wherein the flow rate of the pregnant mare's urine macroporous resin mixed solution on the column is 1 to 4 volumes of horse urine / h, preferably 2 to 3 volumes of horse urine / h.

7. The planting method according to any one of claims 3 to 6, wherein the corn is planted at a spacing of 18 to 20 cm and a row spacing of 45 to 50 cm.

8. The corn product for preventing or improving menopausal symptoms as described in any one of claims 1-2, wherein the product is selected from any one of fresh corn, corn feed, corn kernels, corn grits, corn flour, corn meal, corn tortillas, corn grits, corn germ, corn starch, corn gluten powder, corn steep liquor, corn germ oil, corn cake meal, corn husks, corn syrup, corn flakes, corn wine, and corn popcorn, or a combination thereof.

9. Use of the corn for preventing or improving menopausal symptoms as claimed in any one of claims 1 to 2 in preparing a product for preventing and / or improving menopausal symptoms in patients.

10. A pharmaceutical composition for preventing or improving menopausal syndrome, the composition comprising a drug for preventing and / or treating menopausal syndrome and the corn for preventing or improving menopausal syndrome according to any one of claims 1 to 2.

Citation Information

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