A medicinal and edible composition for improving senile constipation of spleen and lung qi deficiency and a preparation method and application thereof

Abstract

This invention provides a medicinal and edible composition for improving constipation caused by spleen and lung qi deficiency in the elderly, along with its preparation method and application, relating to the field of traditional Chinese medicine composition technology. The composition, by weight, comprises ginseng, astragalus, angelica, hemp seed, apricot kernel, apricot kernel, monk fruit, mulberry, honey, tangerine peel, and poria cocos, obtained through fermentation pretreatment, extraction, concentration, and mixing. This composition significantly improves defecation frequency, stool characteristics, incidence of abdominal distension, intestinal flora, and serum IL-6 levels in subjects, demonstrating great potential in the prevention and treatment of constipation caused by spleen and lung qi deficiency in the elderly.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine composition technology, and relates to improving constipation in the elderly with spleen and lung qi deficiency. Specifically, it relates to a food-medicine homology composition for improving constipation in the elderly with spleen and lung qi deficiency, its preparation method and application. Background Technology

[0002] Functional constipation in the elderly severely impacts their quality of life and can increase the risk of anal fissures, intestinal malignancies, and even trigger cardiovascular and cerebrovascular accidents. In Traditional Chinese Medicine (TCM) theory, functional constipation in the elderly falls under the category of "deficiency constipation," with its core pathogenesis being spleen and lung qi deficiency, resulting in weak propulsion, yin and blood deficiency, and intestinal dryness. This is closely related to the natural decline of organ function in old age. The *Jingyue Quanshu* (Complete Works of Jingyue) states, "Constipation in the elderly…is due to either qi and blood deficiency or depletion of body fluids," clearly indicating that constipation in the elderly is primarily a deficiency syndrome, with spleen and lung qi deficiency being the most common type. Clinical manifestations include difficult and weak defecation, fatigue after defecation, shortness of breath, and poor appetite. Stools are not necessarily hard but difficult to pass, accompanied by pale complexion, fatigue, and lethargy—symptoms of qi deficiency. The course of the disease is protracted, and simple laxatives are insufficient for a complete cure; treatment must address the underlying pathogenesis of spleen and lung qi deficiency.

[0003] Modern medical research indicates that the pathogenesis of constipation in the elderly due to spleen and lung qi deficiency is closely related to abnormal intestinal motility, intestinal flora imbalance, neurotransmitter secretion disorders, and decreased intestinal mucosal barrier function. Spleen qi deficiency can lead to weak intestinal smooth muscle contraction, slowed colonic transit, prolonged fecal retention, and excessive water absorption, resulting in difficulty in defecation. Lung qi deficiency affects the regulatory function of the "lung-large intestine axis," leading to a decrease in the excitatory neurotransmitter substance P and an increase in the inhibitory neurotransmitter nitric oxide, further inhibiting intestinal peristalsis. Simultaneously, spleen and lung qi deficiency can induce intestinal flora imbalance, with a decrease in beneficial bacteria and an increase in harmful bacteria, resulting in damage to the intestinal mucosal barrier and a decline in immune function, forming a vicious cycle of "qi deficiency - intestinal dysfunction - worsened constipation." This aligns with the traditional Chinese medicine theory that "the spleen is the defensive qi; spleen deficiency weakens the defensive qi, leading to intestinal lack of protection and nourishment," further confirming that spleen and lung qi deficiency is the core pathogenesis of functional constipation in the elderly.

[0004] Chinese patent CN104740437A discloses a traditional Chinese medicine composition for treating constipation. The prescription includes Astragalus membranaceus, American ginseng, Rehmannia glutinosa, prepared Rehmannia glutinosa, Atractylodes macrocephala, Cistanche deserticola, Morus alba, stir-fried Citrus aurantium, Magnolia officinalis, Prunus japonica, Cannabis sativa, bitter almond, black sesame, Angelica sinensis, Adenophora stricta, Lycium barbarum, Ophiopogon japonicus, Cinnamomum cassia, Morinda officinalis, Areca catechu, stir-fried chicken gizzard lining, Citrus reticulata peel, stir-fried malt, and charred hawthorn. The preparation method is to pulverize and decoct the herbs to obtain the medicinal liquid.

[0005] Chinese patent CN101480466A discloses a formula and preparation method for a medicine for treating constipation. The formula and preparation method are as follows: 67g of roasted Astragalus membranaceus, 54g of Cistanche deserticola, 45g of Atractylodes macrocephala, 45g of Pseudostellaria heterophylla, 67g of Rehmannia glutinosa, 54g of Scrophularia ningpoensis, 45g of Ophiopogon japonicus, 67g of Angelica sinensis, 45g of processed Polygonatum sibiricum, 45g of Morus alba, 45g of black sesame, 40g of Cannabis sativa seed, 27g of Prunus japonica seed, 36g of Citrus aurantium (stir-fried with wheat bran), and 134g of honey. The above fifteen herbs are prepared by heating the honey to 116-120℃, boiling it, and then filtering it to obtain refined honey. Separately... Codonopsis pilosula is crushed into coarse powder and extracted twice by heating and refluxing with 60% ethanol for one hour each time. The extracts are combined, filtered, and the ethanol is recovered from the filtrate and concentrated to a clear extract with a relative density of 1.02~1.05 (50℃). The residue is decocted twice with the remaining thirteen herbs, including Astragalus membranaceus, for 2 hours the first time and 1.5 hours the second time. The decoctions are combined, filtered, and the filtrate is concentrated to a clear extract with a relative density of 1.10~1.20 (50℃). This extract is then combined with the above clear extract. Refined honey is added, stirred well, and the total volume is adjusted to 1000 ml. The mixture is stirred well, filtered, filled, and sterilized to obtain the final product.

[0006] Current treatments for constipation in the elderly due to spleen and lung qi deficiency have significant limitations, with overall poor efficacy, failing to meet clinical prevention and treatment needs. Western medicine treatments often employ laxatives, prokinetic drugs, and probiotics, which can relieve symptoms in the short term, but long-term use has significant drawbacks: stimulant laxatives easily lead to drug dependence and intestinal motility damage, worsening constipation; bulk-forming laxatives require large amounts of water intake, resulting in poor compliance and ineffectiveness in elderly patients; prokinetic drugs only temporarily improve intestinal peristalsis, failing to replenish spleen and lung qi or nourish intestinal fluids, and have adverse reactions, making them unsuitable for long-term use; probiotics only regulate intestinal flora, lacking specificity for the pathogenesis of spleen and lung qi deficiency, and cannot address both the symptoms and the root cause. Traditional Chinese medicine (TCM) treatment mainly involves herbal decoctions and prepared Chinese medicines. Although it follows the principle of "tonifying qi and strengthening the spleen, moistening the intestines and promoting bowel movements," the decoctions are cumbersome to prepare, have poor taste, and low compliance among elderly patients. Some prepared Chinese medicines have biased formulations that fail to accurately address the core pathogenesis of "spleen and lung qi deficiency and intestinal dryness," resulting in limited efficacy. Furthermore, some Chinese medicines have toxic side effects, and long-term use may increase the burden on liver and kidney function, making them unsuitable for long-term conditioning in elderly patients.

[0007] In summary, constipation due to spleen and lung qi deficiency in the elderly has a high incidence, complex pathogenesis, and prolonged course. Existing treatments have limited efficacy, numerous adverse reactions, and inconvenient administration. There is an urgent need to develop a scientifically formulated, highly targeted, and safe food-medicine homologous composition that combines the effects of invigorating qi and strengthening the spleen, moistening the intestines and relieving constipation, and can be taken for a long time. This would fill the current technological gap and improve the quality of life for elderly patients. Summary of the Invention

[0008] This invention addresses the problems existing in the prior art by providing a medicinal and edible composition for improving constipation in the elderly due to spleen and lung qi deficiency, along with its preparation method and application. The composition, by weight, comprises ginseng, astragalus, angelica, hemp seed, apricot kernel, almond, monk fruit, mulberry, honey, tangerine peel, and poria cocos, obtained through fermentation pretreatment, extraction, concentration, and mixing. This composition can significantly improve defecation frequency, stool characteristics, incidence of abdominal distension, intestinal flora, and serum IL-6 levels in subjects.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows: On the one hand, the present invention provides a composition for improving constipation of the elderly with spleen and lung qi deficiency, the components of which include ginseng, astragalus, angelica, hemp seed, apricot kernel, apricot kernel, monk fruit, mulberry, honey, tangerine peel and poria.

[0010] The above-mentioned composition is both food and medicine, and its formula is explained as follows: Ginseng: Sweet and slightly bitter in taste, slightly warm in nature, it enters the lung, spleen, and heart meridians. It is the chief herb in the formula, and its core function is to greatly replenish vital energy and tonify the spleen and lungs. Targeting the core pathogenesis of constipation in the elderly due to spleen and lung qi deficiency, namely "insufficient qi propulsion," ginseng, being sweet and warm, tonifies qi, strengthens the spleen and stomach, benefits lung qi, and assists in the transmission of qi in the intestines. It fundamentally improves constipation caused by qi deficiency. Its medicinal properties are mild and suitable for the elderly with weak constitutions who cannot tolerate strong tonics.

[0011] Astragalus: Sweet in taste and slightly warm in nature, it enters the lung and spleen meridians and is used as an assistant herb. Its functions include tonifying qi and raising yang, and promoting diuresis and reducing swelling. Its tonifying effect is mild and long-lasting. When combined with ginseng, it enhances the qi-tonifying, spleen-strengthening, and lung-tonifying effects, and strengthens intestinal peristalsis. Its diuretic effect can remove dampness from the spleen and stomach and promote the smooth flow of qi, thus taking into account both tonifying qi and promoting diuresis, avoiding the stagnation caused by simply tonifying qi.

[0012] Angelica sinensis: sweet and pungent in taste, warm in nature, and enters the liver, heart, and spleen meridians. Its functions include nourishing blood, promoting blood circulation, and moistening the intestines to relieve constipation. Targeting the pathogenesis of qi deficiency accompanied by blood deficiency and intestinal dryness in the elderly, Angelica sinensis nourishes blood, promotes blood circulation, and moistens the intestines. When combined with ginseng and astragalus, it achieves the effects of tonifying qi and nourishing blood, moistening the intestines and relieving constipation, thus taking into account both strengthening the body and promoting bowel movement.

[0013] Hemp seeds: sweet in taste, neutral in nature, and enter the spleen, stomach, and large intestine meridians. Their function is to moisten the intestines and relieve constipation. Sweet and neutral in nature, they moisten dryness, lubricate the intestines, and nourish the spleen and stomach. Suitable for long-term use by the elderly, they directly relieve constipation caused by intestinal dryness. They also assist ginseng and astragalus in strengthening the spleen. Fermentation makes them easier to absorb and enhances their laxative effect.

[0014] Prunus japonica seed: It has a pungent, bitter, and sweet taste, and is neutral in nature. It enters the spleen, large intestine, and small intestine meridians. Its functions include moistening the intestines and relieving constipation, and promoting diuresis and reducing swelling. Its laxative effect is stronger than that of hemp seed. It can promote qi circulation, diuresis, and remove dampness from the intestines. When combined with hemp seed, it can synergistically improve constipation in the elderly with qi deficiency accompanied by dampness and qi stagnation.

[0015] Almonds: Sweet and bitter in taste, slightly warm in nature, and enter the lung and large intestine meridians. Their functions include relieving cough and asthma, and moistening the intestines to promote bowel movements. They nourish and clear the lungs, aid in intestinal motility, and moisten the intestines. They also work with hemp seeds and apricot kernels to enhance their laxative effect. Fermentation reduces their cold nature, making them more suitable for the elderly.

[0016] Monk fruit: sweet in taste and cool in nature, it enters the lung and large intestine meridians. Its functions are to clear the lungs and moisten dryness, and to lubricate the intestines and relieve constipation. It is sweet and cool, moistening the intestines and relieving dryness and constipation. At the same time, it harmonizes the properties of the whole formula, neutralizes the warming properties of ginseng and astragalus, and avoids damaging body fluids. It is both a food and a medicine, and has a sweet taste, making it easy for the elderly to take.

[0017] Mulberry: Sweet and sour in taste, cold in nature, enters the heart, liver, and kidney meridians. Its functions include nourishing yin and blood, promoting body fluids and moistening dryness. It nourishes yin and blood, moistens the intestines, relieves constipation caused by qi deficiency accompanied by yin deficiency in the elderly, neutralizes the warming properties of ginseng and astragalus, improves the taste of preparations, and balances tonifying and laxative effects.

[0018] Honey: Sweet in taste, neutral in nature, and enters the lung, spleen, and large intestine meridians. Its functions include tonifying the middle energizer and moistening dryness. It tonifies the middle energizer and strengthens the spleen, moistens dryness and lubricates the intestines to relieve constipation. It also acts as a binder to aid in the shaping of preparations, harmonizes medicinal properties, improves taste, and is suitable for the elderly. Long-term use has no significant side effects.

[0019] Dried tangerine peel: It has a pungent and bitter taste, is warm in nature, and enters the spleen and lung meridians. Its functions include regulating qi and strengthening the spleen, drying dampness and resolving phlegm. It promotes qi circulation and strengthens the spleen, removes dampness from the spleen and stomach, relieves abdominal distension and constipation caused by spleen deficiency and qi stagnation, harmonizes the whole formula, avoids qi stagnation and abdominal distension caused by intestinal lubrication, and achieves the effect of tonifying without stagnation and moistening without greasiness.

[0020] Poria cocos: It has a sweet and bland taste, and is neutral in nature. It enters the heart, lung, spleen, and kidney meridians. Its functions include promoting diuresis and eliminating dampness, and strengthening the spleen. It is sweet and bland, eliminates dampness and strengthens the spleen, removes dampness stagnation in the intestines, and promotes the smooth flow of qi. It assists in strengthening the spleen and replenishing qi. It is neutral in nature, neither drying nor greasy, and does not hinder the moistening of the intestines. It is an important adjuvant medicine for harmonizing the middle jiao in the whole formula.

[0021] Preferably, by weight, the components include 5-10 parts ginseng, 10-30 parts astragalus, 12-18 parts angelica, 10-14 parts hemp seed, 8-12 parts apricot kernel, 6-9 parts almond, 6-9 parts monk fruit, 11-18 parts mulberry, 12-18 parts honey, 4-6 parts dried tangerine peel, and 6-12 parts poria.

[0022] Preferably, the mass ratio of ginseng to astragalus is 1:2-3, and the mass ratio of monk fruit to mulberry is 7:12-14.

[0023] Specifically, by weight, its components include 8 parts ginseng, 16 parts astragalus, 15 parts angelica, 12 parts hemp seed, 10 parts apricot kernel, 8 parts almond, 7 parts monk fruit, 12 parts mulberry, 15 parts honey, 5 parts dried tangerine peel, and 9 parts poria.

[0024] Specifically, by weight, its components include 5 parts ginseng, 15 parts astragalus, 12 parts angelica, 14 parts hemp seed, 8 parts apricot kernel, 9 parts almond, 9 parts monk fruit, 18 parts mulberry, 12 parts honey, 6 parts dried tangerine peel, and 6 parts poria.

[0025] Specifically, by weight, its components include 10 parts ginseng, 20 parts astragalus, 18 parts angelica, 10 parts hemp seed, 12 parts apricot kernel, 6 parts almond, 6 parts monk fruit, 11 parts mulberry, 18 parts honey, 4 parts dried tangerine peel, and 12 parts poria.

[0026] On the other hand, the present invention provides a method for preparing the above composition, comprising the following steps: S1. Fermentation pretreatment: Grind hemp seeds, apricot kernels, and almonds into powder, mix them, add water, inoculate with Lactobacillus plantarum LP45, ferment at 30-37℃ for 24-36 hours, inactivate and dry to obtain three-kernel powder. S2. Extraction Method: Ginseng, Astragalus, Angelica sinensis, tangerine peel, and Poria cocos are crushed, mixed, and 8-10 times their weight of water are added. The mixture is decocted for 2-3 hours, and the volatile oil is collected to obtain the first decoction. The dregs are decocted again for 1-2 hours with 6-8 times their weight of water to obtain the second decoction. The two decoctions are combined to obtain the total decoction. S3. Inclusion of volatile oil: The volatile oil and β-cyclodextrin are mixed at a mass ratio of 1:6-8 and included at 35-40℃ for 2-3 hours to obtain the inclusion complex; S4. Concentration: The total drug solution is concentrated under reduced pressure to a relative density of 1.12-1.18 g / mL to obtain a clear extract; S5. Mixing and granulation: Mix the three-kernel powder, monk fruit powder, mulberry powder with the clear paste and honey, and dry to obtain granules; S6. Total Mixing: Mix the particles with the inclusion complex to obtain the composition.

[0027] Preferably, the preparation method includes the following steps: S1. Fermentation pretreatment: Grind hemp seeds, apricot kernels, and almonds into powder, mix them, add water, inoculate with Lactobacillus plantarum LP45, ferment at 37℃ for 24 hours, inactivate and dry to obtain three-kernel powder. S2. Extraction Method: Ginseng, Astragalus, Angelica, Tangerine Peel, and Poria are crushed, mixed, and 10 times their weight of water are added. The mixture is decocted for 2 hours, and the volatile oil is collected to obtain the first decoction. The dregs are decocted again for 1 hour with 8 times their weight of water to obtain the second decoction. The two decoctions are combined to obtain the total decoction. S3. Inclusion of volatile oil: Volatile oil and β-cyclodextrin were mixed at a mass ratio of 1:8 and included at 40℃ for 2 hours to obtain the inclusion complex; S4. Concentration: The total drug solution is concentrated under reduced pressure to a relative density of 1.12-1.18 g / mL to obtain a clear extract; S5. Mixing and granulation: Mix the three-kernel powder, monk fruit powder, mulberry powder with the clear paste and honey, and dry to obtain granules; S6. Total Mixing: Mix the particles with the inclusion complex to obtain the composition.

[0028] Preferably, the total content of ginsenoside Rg1 and ginsenoside Re in the composition is not less than 0.12 mg / g, the content of astragaloside A is not less than 0.08 mg / g, and the mass fraction of total dietary fiber is not less than 22%.

[0029] Preferably, step S1 includes the following steps: a. Raw material pretreatment: Grind and mix hemp seeds, apricot kernels, and almonds, and pass them through an 80-100 mesh sieve to obtain mixed powder; b. Culture medium preparation: Add purified water to the mixed powder at a material-to-liquid ratio of 1:2-3, stir evenly, autoclave, and cool to room temperature to obtain the culture medium; c. Activation of bacterial strain: Dilute Lactobacillus plantarum LP45 lyophilized powder with sterile water to a concentration of 1×10⁻⁶. 8 -2×10 8 CFU / mL, incubate at 30-37℃ for 30-45 min to obtain activated bacterial solution; d. Inoculation and fermentation: Add 1×10 to the culture medium. 6- 1.5×10 6 Add CFU / mL to the activated bacterial solution, stir well, and let it ferment at 30-37℃ for 24-36 hours. e. Inactivation and drying: After fermentation, inactivate at 70-80℃ for 30-45 minutes, cool and vacuum dry until the moisture content is ≤5-8%, then pulverize and pass through an 80-100 mesh sieve to obtain Sanren powder.

[0030] Preferably, step S1 includes the following steps: a. Raw material pretreatment: Grind and mix hemp seeds, apricot kernels, and almonds, and pass them through an 80-100 mesh sieve to obtain mixed powder; b. Culture medium preparation: Add purified water to the mixed powder at a material-to-liquid ratio of 1:2, stir evenly, autoclave, and cool to room temperature to obtain the culture medium; c. Activation of bacterial strain: Dilute Lactobacillus plantarum LP45 lyophilized powder with sterile water to a concentration of 1×10⁻⁶. 8 CFU / mL, incubate at 37℃ for 30 min to activate the bacterial solution; d. Inoculation and fermentation: Add 1×10 to the culture medium. 6 Add CFU / mL to the activated bacterial solution, stir well, and let ferment at 37℃ for 24 hours. e. Inactivation and drying: After fermentation, inactivate at 80℃ for 30 minutes, cool and vacuum dry until the moisture content is ≤8%, then pulverize and pass through an 80-mesh sieve to obtain Sanren powder.

[0031] Preferably, step S3 includes the following steps: f. Preparation of β-cyclodextrin solution: Weigh β-cyclodextrin according to the mass ratio of volatile oil to β-cyclodextrin = 1:6-8, add 6-8 times the mass of water, heat to 50-60℃ and stir to dissolve to prepare β-cyclodextrin solution; g. Pretreatment of volatile oil: Dilute the volatile oil with anhydrous ethanol at a volume ratio of 1:1-1.5, and add it dropwise to the β-cyclodextrin solution while stirring. h. Constant temperature encapsulation: Maintain 35-40℃ and stir for 2-3 hours for encapsulation; i. Cooling and crystallization: After inclusion, cool to room temperature, then cool to 4-10℃ and let stand for 24-36 hours to precipitate crystals; j. Separation and drying: The crystals are filtered, the filter cake is washed with a small amount of anhydrous ethanol, vacuum dried at 35-40℃ for 6-8 hours, and then pulverized through an 80-100 mesh sieve to obtain the volatile oil inclusion complex.

[0032] Preferably, step S3 includes the following steps: f. Preparation of β-cyclodextrin solution: Weigh β-cyclodextrin according to the mass ratio of volatile oil to β-cyclodextrin = 1:8, add 8 times the mass of water, heat to 60℃ and stir to dissolve, thus preparing β-cyclodextrin solution; g. Pretreatment of volatile oil: Dilute the volatile oil with anhydrous ethanol at a volume ratio of 1:1, and add it dropwise to the β-cyclodextrin solution while stirring. h. Constant temperature encapsulation: Maintain 40℃ and stir for 2 hours for encapsulation; i. Cooling and crystallization: After inclusion, cool to room temperature and let stand at 4°C for 24 hours to precipitate crystals; j. Separation and drying: The crystals are filtered, the filter cake is washed with a small amount of anhydrous ethanol, dried under vacuum at 40°C for 6 hours, and then pulverized through an 80-mesh sieve to obtain the volatile oil inclusion complex.

[0033] On the other hand, the present invention provides the application of the above-described composition or the above-described preparation method in the preparation of products for improving constipation caused by spleen and lung qi deficiency in the elderly.

[0034] Compared with the prior art, the present invention has at least the following beneficial effects: The food-medicine composition provided by this invention can significantly improve the defecation symptoms of constipation in the elderly with spleen and lung qi deficiency, regulate the balance of intestinal flora, reduce the level of chronic intestinal inflammation, and the ginseng and astragalus in the composition have a synergistic effect. Detailed Implementation

[0035] Unless otherwise specified, all raw materials and reagents used in this invention were purchased from commercial suppliers, and experiments were conducted in accordance with the operating instructions. Unless otherwise specified, all instruments, equipment, and apparatus used in this invention are conventional instruments, equipment, and apparatus, and experiments were conducted in accordance with the operating instructions and the accompanying reagents.

[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. Unless otherwise specified in the embodiments, conditions are performed under conventional conditions or conditions recommended by the manufacturer. All reagents or instruments without specified manufacturers are commercially available conventional products. Numerous specific details are provided in the following detailed embodiments to better illustrate the invention. The specific embodiments described herein are for illustrative purposes only and are not intended to constitute any limitation on the invention.

[0037] Data analysis and statistical analysis were performed using professional data processing software. One-way ANOVA was used for significance analysis, and P<0.05 was considered to indicate a significant difference.

[0038] Example 1: Preparation of the composition A medicinal and edible composition for improving constipation in the elderly due to spleen and lung qi deficiency is composed of the following ingredients in parts by weight: ginseng 8 parts, astragalus 16 parts, angelica 15 parts, hemp seed 12 parts, apricot kernel 10 parts, almond 8 parts, monk fruit 7 parts, mulberry 12 parts, honey 15 parts, tangerine peel 5 parts, and poria cocos 9 parts.

[0039] Weigh the raw materials according to the formula and prepare them as follows: 1. Fermentation pretreatment: (1) Raw material pretreatment: Grind hemp seeds, apricot kernels and apricot kernels into powder, pass them through an 80-100 mesh sieve, mix them evenly to obtain a mixed powder; (2) Preparation of culture medium: Add the mixed powder to purified water at a ratio of 1:2 (g / mL), stir evenly, sterilize at 121℃ for 20 min, and cool to room temperature; (3) Activation of bacterial strain: Take Lactobacillus plantarum LP45 lyophilized powder (purchased from Hebei Yiran Biotechnology Co., Ltd.) and dilute it with sterile water to a concentration of 1×10⁻⁶. 8 CFU / mL, activated at 37℃ for 30 min; (4) Inoculation and fermentation: Add 1×10 to the culture medium 6 Add CFU / mL of the activated bacterial solution, stir well, and place in a constant temperature incubator at 37℃ for static fermentation for 24 hours. (5) Inactivation and drying: After fermentation, inactivate in an 80℃ water bath for 30 minutes, cool and then vacuum dry (60℃, -0.08MPa) until the moisture content is ≤8%, then pulverize and pass through an 80-mesh sieve to obtain Sanren powder.

[0040] 2. Double extraction method: Ginseng, Astragalus, Angelica, Tangerine peel and Poria are added to 10 times the weight of water and decocted for 2 hours. The volatile oil is collected and filtered to obtain the first decoction and the residue. The residue is added to 8 times the weight of water and decocted for another hour. The residue is filtered to obtain the second decoction. The two decoctions are combined to obtain the total decoction. 3. Inclusion of volatile oil: The collected volatile oil was included with β-cyclodextrin at a mass ratio of 1:8 at 40℃ for 2 hours to obtain the volatile oil inclusion complex; the specific inclusion method is as follows: (1) Preparation of β-cyclodextrin solution: Weigh β-cyclodextrin according to the mass ratio of volatile oil to β-cyclodextrin = 1:8, add 8 times the mass of purified water, heat to 60℃ and stir to dissolve, and prepare β-cyclodextrin solution; (2) Pretreatment of volatile oil: The collected volatile oil was diluted with anhydrous ethanol at a volume ratio of 1:1 and slowly added dropwise to the β-cyclodextrin solution while stirring. (3) Constant temperature encapsulation: maintain 40℃ and encapsulate with magnetic stirring (300r / min) for 2 hours; (4) Cooling and crystallization: After inclusion, cool naturally to room temperature, refrigerate at 4°C for 24 hours to allow crystals to precipitate; (5) Separation and drying: filter, wash the filter cake three times with a small amount of anhydrous ethanol, dry it under vacuum at 40°C for 6 hours, pulverize it and pass it through an 80-mesh sieve to obtain the volatile oil inclusion complex.

[0041] 4. Concentration: The total liquid obtained in step 2 is concentrated under reduced pressure to a relative density of 1.12-1.18 (at 60℃) to obtain a clear extract; 5. Mixing and granulation: Take the three-kernel powder, monk fruit powder, mulberry coarse powder, clear paste, and honey, mix them and stir evenly. Then, spray dry (inlet air temperature 170-180℃) to granulate and obtain granules. 6. Final mixing: The particles obtained in step 5 are mixed with the volatile oil inclusion complex to obtain the final product.

[0042] Quality control: The finished product contains ginsenoside Rg1+Re≥0.12mg / g, astragaloside A≥0.08mg / g, and total dietary fiber≥22%.

[0043] Example 2: Preparation of the composition A medicinal and edible composition for improving constipation in the elderly due to spleen and lung qi deficiency is composed of the following ingredients in parts by weight: 5 parts ginseng, 15 parts astragalus, 12 parts angelica, 14 parts hemp seed, 8 parts apricot kernel, 9 parts almond, 9 parts monk fruit, 18 parts mulberry, 12 parts honey, 6 parts dried tangerine peel, and 6 parts poria cocos. The preparation method is the same as in Example 1.

[0044] Example 3: Preparation of the composition A medicinal and edible composition for improving constipation in the elderly due to spleen and lung qi deficiency is composed of the following ingredients in parts by weight: 10 parts ginseng, 20 parts astragalus, 18 parts angelica, 10 parts hemp seed, 12 parts apricot kernel, 6 parts almond, 6 parts monk fruit, 11 parts mulberry, 18 parts honey, 4 parts dried tangerine peel, and 12 parts poria cocos. The preparation method is the same as in Example 1.

[0045] Comparative Example 1: Preparation of the Composition Prepared according to the method of Example 1, except that ginseng is replaced with an equal mass of astragalus; that is, the weight of ginseng is 0 parts and the weight of astragalus is 24 parts, otherwise it is the same as Example 1.

[0046] Comparative Example 2: Preparation of the Composition Prepared according to the method of Example 1, except that Astragalus membranaceus is replaced with an equal mass of ginseng; that is, the weight parts of ginseng are 24 parts and the weight parts of Astragalus membranaceus are 0 parts, and everything else is the same as in Example 1.

[0047] Comparative Example 3: Preparation of the Composition Prepared according to the method of Example 1, except that the weight parts of Astragalus and Ginseng are both 0, and the rest is the same as in Example 1.

[0048] Comparative Example 4: Preparation of the Composition Prepared according to the method of Example 1, except that Poria cocos is replaced with an equal mass of Dioscorea opposita, otherwise the same as in Example 1.

[0049] Comparative Example 5: Preparation of the Composition Prepared according to the method of Example 1, except that the weight parts of ginseng are 4 parts and the weight parts of astragalus are 20 parts, otherwise the same as in Example 1.

[0050] Comparative Example 6: Preparation of the Composition Prepared according to the method of Example 1, except that the weight parts of monk fruit are 10 parts and the weight parts of mulberry are 9 parts, otherwise the same as in Example 1.

[0051] Comparative Example 7: Preparation of the Composition The medicine was prepared according to the scheme of Example 1 of Chinese Patent CN104740437A: the raw materials were combined in the following weight proportions: Astragalus membranaceus 30g, American ginseng 6g, Rehmannia glutinosa 30g, prepared Rehmannia glutinosa 30g, Atractylodes macrocephala 20g, Cistanche deserticola 30g, Morus alba 20g, stir-fried Citrus aurantium 12g, Magnolia officinalis 6g, Prunus japonica 30g, Cannabis sativa 20g, Prunus armeniaca 20g, black sesame 45g, Angelica sinensis 30g, Adenophora stricta 20g, Lycium barbarum 20g, Ophiopogon japonicus 20g, Cinnamomum cassia 12g, Morinda officinalis 10g, Areca catechu 30g, stir-fried chicken gizzard lining 9g, Citrus reticulata 20g, stir-fried malt 20g, and charred hawthorn 20g; the medicine was granulated by pulverizing and decocting, followed by spray drying (air inlet temperature 170-180℃).

[0052] Example 1: Safety Study 1.1 90-day oral feeding toxicity test This experiment was conducted in accordance with GB 15193.13-2015 "National Food Safety Standard 90-day Oral Toxicity Test" to verify the long-term toxicity and safety of the food-medicine homology composition of the present invention.

[0053] Specific experimental protocol: 110 SPF-grade SD rats (6-7 weeks old, weighing 180-220g), half male and half female, were selected and randomly divided into 11 groups of 10 rats each (5 males and 5 females) after 7 days of acclimatization. The control group was administered purified water by gavage, while the other groups were administered the corresponding compositions of Examples 1-3 and Comparative Examples 1-7 by gavage. Each group of rats was administered the corresponding dose of the test substance orally by gavage daily at a dose of 5g / kg·d for 90 consecutive days. During this period, the rats had free access to food and water. During the experiment, the rats' general physical signs, behavior, fur condition, diet, and fecal characteristics were observed daily; rat weight and food intake were measured weekly. At the end of the experiment, blood was collected from the abdominal aorta to detect complete blood count and blood biochemical indicators. After 90 days, the rats were dissected, and major organs such as the heart, liver, spleen, lungs, kidneys, and gastrointestinal tract were harvested, weighed, and organ coefficients were calculated. Histopathological examination of each organ was also performed.

[0054] Experimental Results: Compared with the control group, rats in each dosage group were in good general condition, with no abnormal behavior, smooth fur, and normal diet and feces; there were no significant differences in body weight, food intake, blood routine indicators, blood biochemical indicators, and organ coefficients (P>0.05); no obvious pathological damage was found in the histopathological examination of each organ. This indicates that in the 90-day feeding experiment of the food-medicine homology composition of this invention in rats, no adverse effect level (NOAEL) > 5 g / kg·d was observed, and there were no obvious toxic side effects, demonstrating good safety.

[0055] 1.2 Ames test (Salmonella typhimurium reverse mutation test) This experiment was conducted in accordance with GB 15193.4-2015 "National Food Safety Standard Bacterial Reversion Mutation Test" to verify the mutagenicity of the food-medicine homology composition of the present invention.

[0056] Specific experimental protocol: The plate incorporation method was used, employing four standard strains of histidine auxotrophic Salmonella typhimurium: TA97, TA98, TA100, and TA102. Five dose groups of the test substance were set up: 5000, 1000, 200, 40, and 8 μg / plate. Simultaneously, a blank control group, a solvent control group, and a positive mutagen control group were set up (2-aminofluorene was the positive control for TA97 and TA98 strains, sodium azide was the positive control for TA100 strain, and mitomycin C was the positive control for TA102 strain). Each group was tested independently, with and without the addition of the S9 metabolic activation system. Each dose of test substance, strain, culture medium, and S9 metabolic solution (if necessary) were thoroughly mixed, spread onto plates, and incubated at 37°C for 48 hours. The number of revertant colonies per plate was then counted. Experimental judgment criteria: A test substance group was considered positive for mutagenicity if the number of revertant colonies was more than twice that of the control group and a clear dose-response relationship was observed; otherwise, it was considered negative.

[0057] Experimental results: The compositions corresponding to Examples 1-3 and Comparative Examples 1-7, under the conditions of adding and not adding the S9 metabolic activation system, all showed revertant colony counts within the normal range, with no significant difference compared to the blank control group and the solvent control group, and no obvious dose-response relationship, indicating that the Ames test results of the food-medicine homology composition provided by the present invention were negative and had no mutagenicity.

[0058] Example 2: Verification of the efficacy in treating constipation in the elderly with spleen and lung qi deficiency Experimental objective: To verify the therapeutic effect of the food-medicine homology composition of the present invention on constipation of elderly patients with spleen and lung qi deficiency, and to clarify its effects on defecation-related indicators, intestinal flora and serum inflammatory factors.

[0059] Experimental Design: Two hundred subjects aged 60-78 years who met the diagnostic criteria for constipation due to spleen and lung qi deficiency in the elderly were selected. All subjects signed informed consent forms, and those with severe liver and kidney dysfunction, organic gastrointestinal diseases, or allergies to any ingredient in the composition of this invention were excluded. They were randomly divided into 10 groups of 20 subjects each, and were given the compositions corresponding to Examples 1-3 or Comparative Examples 1-7, 10g twice daily, dissolved in warm water, for 4 consecutive weeks. Various indicators were recorded or measured before and after 4 weeks of treatment to evaluate the therapeutic effect. The diagnostic criteria for constipation due to spleen and lung qi deficiency in the elderly are as follows: (1) Age: ≥60 years old; (2) Course of disease: Symptoms have been present for ≥6 months and have persisted for the past 3 months; (3) Core symptoms (meeting ≥2 items): a) ≥25% of people experience difficulty defecating; b. ≥25% of stool is dry / hard stool (Bristol type 1–2); c. ≥25% of people experience a feeling of incomplete bowel movement; d. ≥25% of bowel movements involve a feeling of anal or rectal obstruction / blockage; e. ≥25% of defecation requires manual assistance (finger scraping, pelvic floor support); f. Spontaneous bowel movements less than 3 times per week.

[0060] (4) Exclusion criteria: constipation caused by organic lesions, drugs, or metabolic / endocrine diseases.

[0061] 2.1 Clinical compliance Four weeks after administration, a questionnaire survey was used to evaluate the taste acceptance of the subjects. The taste evaluation was divided into five levels: very good, good, average, poor, and very poor. The good taste rate was calculated (the proportion of subjects with a taste evaluation of very good or good out of the total number of subjects). The results showed that the good taste rate in each group was above 90%. No adverse events such as nausea, diarrhea, or dry mouth occurred during the trial, and no serious adverse events occurred, indicating that the food-medicine homology composition of the present invention has a good taste and good clinical compliance.

[0062] 2.2 Bowel movement frequency Measurement method: One week before the trial, each subject was instructed to accurately record the number of spontaneous bowel movements and the average number of spontaneous bowel movements within one week was calculated. After 4 weeks of treatment, the average number of spontaneous bowel movements within one week was calculated and the changes in bowel movement frequency before and after the intervention were compared. The results are shown in Table 1.

[0063] Table 1. Weekly statistics on the number of times a person defecates independently.

[0064] Note: * indicates that there is no significant difference between the data in this column (P>0.05); for data in the same column, the same letter indicates no significant difference (P>0.05), and different letters indicate significant differences (P<0.05).

[0065] 2.3. Characteristics of feces Measurement Methods: The Bristol Stool Characteristics Scale (BSFS) was used to grade stool characteristics. The specific grading criteria were as follows: Type 1 (hard, nut-like) = 1 point; Type 2 (sausage-like but with lumps) = 2 points; Type 3 (sausage-like with cracks on the surface) = 3 points; Type 4 (smooth sausage or snake-like) = 4 points; Type 5 (soft lumps with clear edges) = 5 points; Type 6 (pasty stool) = 6 points; Type 7 (watery stool) = 7 points. Types 3 and 4 are considered normal stool characteristics, and the goal for constipation improvement was to change stool characteristics to Type 3 or 4. During the trial, the subjects' stool characteristics were recorded daily according to their corresponding grades. The average grade scores were calculated one week before and one week after the intervention. The average grade scores were also statistically analyzed one week before and four weeks after the intervention to compare the improvement in stool characteristics before and after the intervention. The results are shown in Table 2.

[0066] Table 2. Statistical analysis of weekly stool characteristics

[0067] Note: * indicates that there is no significant difference between the data in this column (P>0.05); for data in the same column, the same letter indicates no significant difference (P>0.05), and different letters indicate significant differences (P<0.05).

[0068] 2.4 Incidence of abdominal distension Measurement Method: During the experiment, the occurrence of abdominal distension in the subjects was recorded daily. The grading criteria for abdominal distension were: no abdominal distension, mild abdominal distension (occasional abdominal distension, not affecting normal life), moderate abdominal distension (frequent abdominal distension, affecting appetite), and severe abdominal distension (persistent abdominal distension, accompanied by abdominal pain and nausea). The number of subjects experiencing abdominal distension was counted on the day before and the day after the intervention. The abdominal distension incidence rate was calculated using the formula "Incidence rate of abdominal distension (%) = (Number of subjects experiencing abdominal distension / Total number of subjects) × 100%". The changes in the incidence rate of abdominal distension before and after the intervention were compared. The results are shown in Table 3.

[0069] Table 3. Statistics on the incidence of abdominal distension

[0070] 2.5. Gut microbiota (16S rRNA) Assay method: Before and after the intervention, approximately 2g of fresh fecal samples were collected from each subject and placed in sterile centrifuge tubes, frozen at -80℃ to avoid repeated freeze-thaw cycles. Bacterial genomic DNA was extracted from the fecal samples using a bacterial genomic DNA extraction kit, strictly following the kit instructions. Using the extracted DNA as a template, the bacterial 16S rRNA gene was amplified, sequenced, and classified and annotated. The percentage of Bifidobacterium species was calculated to clarify the regulatory effect of the composition of this invention on the intestinal flora structure. The results are shown in Table 4.

[0071] Table 4. Percentage statistics of Bifidobacteria

[0072] Note: * indicates that there is no significant difference between the data in this column (P>0.05); for data in the same column, the same letter indicates no significant difference (P>0.05), and different letters indicate significant differences (P<0.05).

[0073] 2.6 Serum IL-6 Measurement method: Serum IL-6 levels of subjects were measured using an ELISA kit (Yisheng Biotechnology, catalog number 97068ES96) one day before intervention and one day after intervention 4 weeks later. The changes in serum IL-6 levels before and after intervention were compared. The results are shown in Table 5.

[0074] Table 5. Serum IL-6 Statistics

[0075] Note: * indicates that there is no significant difference between the data in this column (P>0.05); for data in the same column, the same letter indicates no significant difference (P>0.05), and different letters indicate significant differences (P<0.05).

[0076] In summary, after 4 weeks of intervention, compared with comparative groups 1-7, the subjects in Examples 1-3 showed a significant increase in average weekly defecation frequency, a significant increase in fecal characteristics Bristol scores, a significant decrease in the incidence of abdominal distension, a significant increase in the abundance of Bifidobacterium spp. (a probiotic) in the gut microbiota, and a significant decrease in serum IL-6 levels. This indicates that the food-medicine homology composition of the present invention can effectively improve defecation symptoms in elderly patients with spleen and lung qi deficiency type constipation, regulate gut microbiota balance, and reduce the level of chronic intestinal inflammation, demonstrating significant therapeutic effects. Among them, compared with comparative examples 1 and 2, the improvement effect of Example 1 was significantly improved, indicating that ginseng and astragalus have a synergistic effect. Moreover, after replacing the components or changing the proportions between the components, the effect significantly worsened, further demonstrating that the composition of the present invention works as a whole and cannot be obtained through conventional screening.

[0077] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for improving constipation in the elderly due to spleen and lung qi deficiency, characterized in that, Its ingredients include ginseng, astragalus, angelica, hemp seed, apricot kernel, almond, monk fruit, mulberry, honey, dried tangerine peel, and poria.

2. The composition according to claim 1, characterized in that, By weight, its components include 5-10 parts ginseng, 10-30 parts astragalus, 12-18 parts angelica, 10-14 parts hemp seed, 8-12 parts apricot kernel, 6-9 parts apricot kernel, 6-9 parts monk fruit, 11-18 parts mulberry, 12-18 parts honey, 4-6 parts dried tangerine peel, and 6-12 parts poria.

3. The composition according to claim 2, characterized in that, The mass ratio of ginseng to astragalus is 1:2-3, and the mass ratio of monk fruit to mulberry is 7:12-14.

4. The composition according to claim 3, characterized in that, By weight, its components include 8 parts ginseng, 16 parts astragalus, 15 parts angelica, 12 parts hemp seed, 10 parts apricot kernel, 8 parts almond, 7 parts monk fruit, 12 parts mulberry, 15 parts honey, 5 parts dried tangerine peel, and 9 parts poria.

5. The composition according to claim 3, characterized in that, By weight, its components include 5 parts ginseng, 15 parts astragalus, 12 parts angelica, 14 parts hemp seed, 8 parts apricot kernel, 9 parts almond, 9 parts monk fruit, 18 parts mulberry, 12 parts honey, 6 parts dried tangerine peel, and 6 parts poria.

6. The composition according to claim 3, characterized in that, By weight, its components include 10 parts ginseng, 20 parts astragalus, 18 parts angelica, 10 parts hemp seed, 12 parts apricot kernel, 6 parts almond, 6 parts monk fruit, 11 parts mulberry, 18 parts honey, 4 parts dried tangerine peel, and 12 parts poria.

7. A method for preparing the composition according to any one of claims 1-6, characterized in that, Includes the following steps: S1. Fermentation pretreatment: Grind hemp seeds, apricot kernels, and almonds into powder, mix them, add water, inoculate with Lactobacillus plantarum LP45, ferment at 30-37℃ for 24-36 hours, inactivate and dry to obtain three-kernel powder. S2. Extraction Method: Ginseng, Astragalus, Angelica sinensis, tangerine peel, and Poria cocos are crushed, mixed, and 8-10 times their weight of water are added. The mixture is decocted for 2-3 hours, and the volatile oil is collected to obtain the first decoction. The dregs are decocted again for 1-2 hours with 6-8 times their weight of water to obtain the second decoction. The two decoctions are combined to obtain the total decoction. S3. Inclusion of volatile oil: The volatile oil and β-cyclodextrin are mixed at a mass ratio of 1:6-8 and included at 35-40℃ for 2-3 hours to obtain the inclusion complex; S4. Concentration: The total drug solution is concentrated under reduced pressure to a relative density of 1.12-1.18 g / mL to obtain a clear extract; S5. Mixing and granulation: Mix the three-kernel powder, monk fruit powder, mulberry powder with the clear paste and honey, and dry to obtain granules; S6. Total Mixing: Mix the particles with the inclusion complex to obtain the composition.

8. The preparation method according to claim 7, characterized in that, Step S1 includes the following steps: a. Raw material pretreatment: Grind and mix hemp seeds, apricot kernels, and almonds, and pass them through an 80-100 mesh sieve to obtain mixed powder; b. Culture medium preparation: Add purified water to the mixed powder at a material-to-liquid ratio of 1:2-3, stir evenly, autoclave, and cool to room temperature to obtain the culture medium; c. Strain activation: Take Lactobacillus plantarum LP45 freeze-dried powder and dilute with sterile water to 1 x 10 8 -2 x 10 8 CFU / mL, stand at 30-37°C for 30-45 min to obtain activated bacterial solution; d. Inoculation and fermentation: Add 1×10 to the culture medium. 6- 1.5×10 6 Add CFU / mL to the activated bacterial solution, stir well, and let it ferment at 30-37℃ for 24-36 hours. e. Inactivation and drying: After fermentation, inactivate at 70-80℃ for 30-45 minutes, cool and vacuum dry until the moisture content is ≤5-8%, then pulverize and pass through an 80-100 mesh sieve to obtain Sanren powder.

9. The preparation method according to claim 7, characterized in that, Step S3 includes the following steps: f. Preparation of β-cyclodextrin solution: Weigh β-cyclodextrin according to the mass ratio of volatile oil to β-cyclodextrin = 1:6-8, add 6-8 times the mass of water, heat to 50-60℃ and stir to dissolve to prepare β-cyclodextrin solution; g. Pretreatment of volatile oil: Dilute the volatile oil with anhydrous ethanol at a volume ratio of 1:1-1.5, and add it dropwise to the β-cyclodextrin solution while stirring. h. Constant temperature encapsulation: Maintain 35-40℃ and stir for 2-3 hours for encapsulation; i. Cooling and crystallization: After inclusion, cool to room temperature, then cool to 4-10℃ and let stand for 24-36 hours to precipitate crystals; j. Separation and drying: The crystals are filtered, the filter cake is washed with a small amount of anhydrous ethanol, vacuum dried at 35-40℃ for 6-8 hours, and then pulverized through an 80-100 mesh sieve to obtain the volatile oil inclusion complex.

10. The use of the composition according to any one of claims 1-6 or the preparation method according to any one of claims 7-9 in the preparation of a product for improving constipation caused by spleen and lung qi deficiency in the elderly.

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