Composition for treating yin deficiency constipation as well as preparation method and application thereof

Abstract

The invention provides a composition for treating yin deficiency constipation and a preparation method and application thereof, and belongs to the technical field of pharmaceutical compositions. The composition for treating yin deficiency constipation is prepared from radix rehmanniae recen, radix ophiopogonis, radix glehniae, fructus cannabis, semen pruni, semen boitae, radix astragali, roasted rhizoma atractylodis macrocephalae and fructus perillae. The three monarch drugs synergistically nourish lung yin, stomach yin and kidney yin, yin fluid is supplemented from the source, and the foundation of'water increasing and boat running 'is built; the three ministerial drugs are complementary and synergistic, and lubricate intestinal tracts; astragalus mongholicus and roasted rhizoma atractylodis macrocephalae are used as adjuvant drugs to tonify qi and spleen, prevent the monarch drugs from being sweet, cold, greasy and obstructing stomach, and tonify qi and promote intestinal The traditional Chinese medicine is scientific in compatibility of the medicines, mild in medicine property, capable of giving consideration to both cold and heat and tonifying and reducing, and suitable for old people, postpartum women, weak people after long illness and patients after radiotherapy and chemotherapy.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical composition technology, and particularly relates to a composition for treating constipation due to yin deficiency, its preparation method and uses. Background Technology

[0002] Constipation is a common digestive system disorder in clinical practice. Yin deficiency constipation, as a common syndrome in Traditional Chinese Medicine (TCM), is often caused by a deficiency of Yin fluids in the body, resulting in insufficient lubrication of the intestines and impaired intestinal motility. TCM believes that the core pathogenesis of Yin deficiency constipation is insufficiency of the Yin of the lungs, stomach, and kidneys, leading to depletion of body fluids and blood, intestinal dryness, and sometimes accompanied by Qi deficiency and weak propulsion. Clinically, it mainly manifests as dry, hard stools resembling sheep pellets, difficulty in defecation, and fatigue after defecation, often accompanied by symptoms of Yin deficiency such as dry mouth and throat, night sweats, red tongue with little coating, and a thready, rapid pulse. This condition is common in the elderly, postpartum women, those with chronic illnesses and weakened constitutions, and patients undergoing radiotherapy and chemotherapy. These individuals are generally weak and intolerant to cold and strong purgatives. Long-term constipation not only affects their quality of life but may also induce complications such as hemorrhoids and anal fissures. Therefore, there is an urgent clinical need for a mild, effective combination of herbs that nourish Yin, moisten the intestines, and replenish Qi to treat Yin deficiency constipation.

[0003] Currently, most clinical and existing formulations for treating constipation due to yin deficiency focus on nourishing yin and moistening the intestines, but they still have significant shortcomings: First, the formulations are not comprehensive enough. Most formulations only focus on nourishing yin or moistening the intestines, failing to address the complex pathogenesis of yin deficiency and fluid depletion combined with qi deficiency and weak bowel movement. Either long-term use can easily obstruct the spleen and stomach's digestive function due to their sweet, cold, and greasy nature, or they lack sufficient propulsive force for defecation. Second, the balance of medicinal properties is poorly controlled. Some formulas are too cold, easily damaging the spleen and stomach's yang qi, while others are too warm, exacerbating yin deficiency and internal heat. Neither is suitable for individuals with weak constitutions and constipation due to yin deficiency. These problems limit the clinical applicability of existing formulations and result in poor overall therapeutic effects, failing to meet actual clinical needs. Therefore, developing a scientifically formulated and highly effective formulation for treating constipation due to yin deficiency has significant clinical importance and application value. Summary of the Invention

[0004] In order to address the problems existing in the prior art, the present invention provides a composition for treating constipation due to yin deficiency, a method for preparing the composition, and its uses.

[0005] To address this, the present invention adopts the following technical solution: This invention relates to a composition for treating constipation due to yin deficiency, comprising the following ingredients: Rehmannia glutinosa, Ophiopogon japonicus, Adenophora stricta, Cannabis sativa seed, Prunus japonica seed, Platycladus orientalis seed, Astragalus membranaceus, Atractylodes macrocephala (fried), and Perilla frutescens seed.

[0006] Principal drug: Rehmannia glutinosa: sweet and cold; enters the heart, liver, and kidney meridians; pharmacopoeia efficacy: nourishes yin and generates fluids, clears heat and cools blood; in the formula: nourishes kidney yin and replenishes true yin, serving as the core medicinal material for nourishing yin and increasing fluids, replenishing the yin fluids needed to moisten the intestines from the root, achieving "increasing water to move the boat", while also clearing heat and generating fluids, improving symptoms of yin deficiency with dry mouth and throat.

[0007] Ophiopogon japonicus: sweet, slightly bitter, slightly cold; enters the heart, lung, and stomach meridians; pharmacopoeia efficacy: nourishes yin and generates fluids, moistens the lungs and clears the heart; in the formula: nourishes the yin of the lungs and stomach, replenishes lung yin to facilitate descending and purifying, replenishes stomach yin to aid digestion, and when combined with Rehmannia glutinosa, it achieves simultaneous replenishment of the yin of the lungs, stomach, and kidneys, enhancing the effect of nourishing yin and increasing fluids.

[0008] North American ginseng: sweet, slightly bitter, slightly cold; enters the lung and stomach meridians; functions: nourishes yin and clears the lungs, benefits the stomach and generates fluids; in the formula: specifically replenishes lung and stomach yin deficiency, nourishing without being greasy, avoiding the principal herb's excessive yin nourishment that obstructs the spleen and stomach, while working with Ophiopogon japonicus to strengthen the replenishment of lung and stomach yin fluids, and when lung yin is sufficient, the large intestine's transmission is strong.

[0009] Minister's Medicine: Hemp seed: sweet, neutral; enters the spleen, stomach, and large intestine meridians; function: moistens the intestines and promotes bowel movement; in the formula: it is moist and oily, and gently lubricates the intestines, making it an essential medicine for moistening the intestines and promoting bowel movement. It is not drastic and does not damage the yin fluid, making it suitable for the mild treatment needs of constipation due to yin deficiency.

[0010] Prunus japonica seed: pungent, bitter, sweet, neutral; enters the spleen, large intestine, and small intestine meridians; functions: moistens the intestines and promotes bowel movement, lowers qi and promotes urination; in the formula: moistens the intestines and promotes bowel movement while lowering qi and relieving stagnation, solves the problem of constipation due to yin deficiency and intestinal qi stagnation and difficulty in defecation, and enhances the effect of moistening the intestines and relieving stagnation when combined with hemp seed.

[0011] Arborvitae seed: sweet, neutral; enters the heart, kidney, and large intestine meridians; functions: nourishes the heart and calms the mind, moistens the intestines and promotes bowel movement; in the formula: nourishes blood and moistens the intestines, while also nourishing the heart, suitable for patients with yin deficiency constipation accompanied by insomnia and palpitations. At the same time, when combined with hemp seed and apricot seed, it achieves the dual effects of nourishing blood and moistening the intestines, avoiding damage to blood due to moistening the intestines.

[0012] Adjuvant: Astragalus: sweet, slightly warm; enters the spleen and lung meridians; classic effects: tonifies qi and raises yang, consolidates the exterior and stops sweating, promotes diuresis and reduces swelling, generates fluids and nourishes blood; function in the formula: tonifies the middle and benefits qi, tonifies the qi of the spleen and stomach to promote intestinal transmission, solves the complex pathogenesis of "qi deficiency and weak propulsion" in yin deficiency constipation, and at the same time tonifies qi and generates fluids, and assists in nourishing yin and increasing fluids.

[0013] Stir-fried Atractylodes macrocephala: sweet, bitter, warm; enters the spleen and stomach meridians; functions: strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating; role in the formula: after stir-frying, the spleen-strengthening and qi-replenishing effects are enhanced, and it dries dampness without depleting yin. When combined with Astragalus membranaceus, it forms a classic combination of qi-replenishing and spleen-strengthening, preventing the sweet, cold, and greasy nature of the principal herb from hindering the spleen and stomach's digestive function. When the spleen and stomach are in harmony, the generation of yin fluids is abundant.

[0014] Used medicine: Perilla seed: pungent, warm; enters the lung and large intestine meridians; functions: lowers qi and resolves phlegm, stops cough and relieves asthma, moistens the intestines and promotes bowel movement; its role in the formula: lowers lung qi and unblocks the large intestine, following the theory of "the lung and large intestine are internally and externally related", guiding the entire formula's medicinal power downwards directly to the large intestine, acting as a guiding herb in the formula to achieve simultaneous treatment of the lung and intestines; it is moist and oily, assisting the assistant herbs hemp seed, apricot seed, and cypress seed to enhance the effect of moistening the intestines and promoting bowel movement, taking into account both lowering qi and promoting bowel movement, suitable for the complex pathogenesis of yin deficiency constipation, intestinal dryness and qi stagnation; its medicinal nature is warm but not dry, echoing the warm nature of the adjuvant herbs astragalus and stir-fried atractylodes, balancing the sweet, cold and greasy nature of the principal herbs, maintaining the balance of cold and heat in the whole formula, making the effect of promoting bowel movement gentle and lasting.

[0015] Further, the raw materials of the composition are formulated in the following weight ratios: 15-25 parts of Rehmannia glutinosa, 10-15 parts of Ophiopogon japonicus, 10-15 parts of Adenophora stricta, 8-12 parts of Cannabis sativa seed, 6-10 parts of Prunus japonica seed, 8-12 parts of Platycladus orientalis seed, 6-12 parts of Astragalus membranaceus, 6-10 parts of Atractylodes macrocephala (fried), and 5-8 parts of Perilla frutescens seed.

[0016] Further, the raw materials of the composition are formulated in the following weight ratios: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0017] In another aspect, the present invention provides a method for preparing a composition for treating constipation due to yin deficiency, comprising the following steps: Weigh the pulverized raw materials, add water, soak them, and then decoct them twice. Combine the filtrates from the second decoction and concentrate them to obtain the composition.

[0018] The preparation method is specifically as follows: Weigh the pulverized raw material, add 10 times the volume of water to the raw material, soak for 1 hour, heat to boiling, continue to simmer for 30 minutes, filter, add 10 times the volume of water to the filtered residue and simmer for 30 minutes, filter, combine the filtrates, concentrate to a crude drug equivalent of 0.2 g / mL, and obtain the extract of the composition.

[0019] Furthermore, the decoction temperature is 90-100℃, and a gentle boil is maintained during the decoction process, with stirring every 10 minutes; the filtration uses a 100-200 mesh filter to remove medicinal residue and impurities.

[0020] The final aspect of this invention provides the use of the composition for treating constipation due to yin deficiency in the preparation of a medicine having a laxative function.

[0021] Furthermore, the dosage form of the medicine is tablets, powders, capsules, decoctions, granules, or pills.

[0022] Furthermore, the drug is used to treat constipation due to yin deficiency and intestinal dryness in the elderly, postpartum constipation due to yin deficiency, or constipation due to yin deficiency after radiotherapy or chemotherapy.

[0023] The beneficial effects of this invention are: This invention discloses a composition for treating constipation due to yin deficiency. It uses Rehmannia glutinosa, Ophiopogon japonicus, and Adenophora stricta as the principal herbs, Cannabis sativa seed, Prunus japonica seed, and Platycladus orientalis seed as the assistant herbs, Astragalus membranaceus and Atractylodes macrocephala (fried) as adjuvant herbs, and Perilla frutescens seed as the guiding herb. Utilizing the synergistic effects of the efficacy and dosage of each herb, it combines nourishing yin and replenishing fluids, lubricating the intestines and promoting bowel movements, and tonifying qi and strengthening the spleen, ultimately achieving a significant and gentle therapeutic effect. The three principal herbs work together to nourish the yin of the lungs, stomach, and kidneys, replenishing yin fluids from the root and strengthening the foundation. The three assistant herbs complement each other, enhancing the effect and lubricating the intestines. The adjuvant herbs Astragalus membranaceus and Atractylodes macrocephala (fried) tonify qi and strengthen the spleen, preventing the sweet, cold, and greasy nature of the principal herbs from hindering stomach function, while simultaneously tonifying qi and promoting intestinal motility. The guiding herb Perilla frutescens lowers lung qi and clears the large intestine, treating both the lungs and intestines to enhance the bowel-regulating effect. The combination of herbs is scientific, the medicinal properties are mild, and it balances cold and heat, tonifying and purging, making it suitable for the elderly, postpartum women, those with chronic illness and weakness, and patients undergoing radiotherapy and chemotherapy. Attached Figure Description

[0024] Figure 1 The results show the time to first black stool in mice of Examples 1-3 and Comparative Examples 1-7; Figure 2 The results show the time to first black stool in mice of control group 8-16. Figure 3 The results of the number of fecal particles in mice of Examples 1-3 and Comparative Examples 1-7 after 6 hours; Figure 4 The results show the number of fecal particles in mice of Comparative Example 8-16 after 6 hours. Figure 5 The results show the fecal water content of mice in Examples 1-3 and Comparative Examples 1-7. Figure 6 The results show the fecal water content of mice in Comparative Examples 8-16. Detailed Implementation

[0025] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, the raw materials, reagents, or apparatus used in the following embodiments are readily available from conventional commercial sources or can be obtained by existing known methods. Experimental methods not specifically described are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, parts and percentages are parts by weight and weight percentages.

[0026] Example 1: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0027] The composition was prepared according to the following method: Weigh the pulverized raw materials, add 10 times their volume of water, soak for 1 hour, then heat to boiling and continue simmering over low heat for 30 minutes, maintaining a gentle boil (simmering temperature 100℃) and stirring every 10 minutes. After simmering, remove the dregs and impurities through a 100-200 mesh filter to obtain the first filtrate and residue. Add 10 times their volume of water to the residue and simmer for a second time for 30 minutes, maintaining a gentle boil and stirring every 10 minutes. After simmering, remove the dregs and impurities through a 100-200 mesh filter to obtain the second filtrate. Combine the first and second filtrates and concentrate to a crude drug equivalent of 0.2 g / mL. Vacuum dry to obtain a dry extract for later use.

[0028] Example 2: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 15 parts Rehmannia glutinosa, 10 parts Ophiopogon japonicus, 10 parts Adenophora stricta, 8 parts Cannabis sativa, 6 parts Prunus japonica, 8 parts Platycladus orientalis, 6 parts Astragalus membranaceus, 6 parts Atractylodes macrocephala (fried), and 5 parts Perilla frutescens.

[0029] The preparation method of the composition is the same as in Example 1.

[0030] Example 3: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 25 parts Rehmannia glutinosa, 15 parts Ophiopogon japonicus, 15 parts Adenophora stricta, 12 parts Cannabis sativa, 10 parts Prunus japonica, 12 parts Platycladus orientalis, 12 parts Astragalus membranaceus, 10 parts Atractylodes macrocephala (fried), and 8 parts Perilla frutescens.

[0031] The preparation method of the composition is the same as in Example 1.

[0032] Comparative Example 1: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 10 parts Cannabis sativa seed, 8 parts Prunus japonica seed, 10 parts Platycladus orientalis seed, 9 parts Astragalus membranaceus, 8 parts stir-fried Atractylodes macrocephala, and 6 parts Perilla frutescens seed.

[0033] Compared with Example 1, this comparative example did not use North American ginseng as a raw material.

[0034] The preparation method of the composition is the same as in Example 1.

[0035] Comparative Example 2: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 12 parts of Ophiopogon japonicus, 13 parts of Adenophora stricta, 10 parts of Cannabis sativa seed, 8 parts of Prunus japonica seed, 10 parts of Platycladus orientalis seed, 9 parts of Astragalus membranaceus, 8 parts of stir-fried Atractylodes macrocephala, and 6 parts of Perilla frutescens seed.

[0036] Compared with Example 1, this comparative example did not use Rehmannia glutinosa as a raw material.

[0037] The preparation method of the composition is the same as in Example 1.

[0038] Comparative Example 3: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 12 parts of Ophiopogon japonicus, 10 parts of hemp seed, 8 parts of Prunus japonica seed, 10 parts of Platycladus orientalis seed, 9 parts of Astragalus membranaceus, 8 parts of stir-fried Atractylodes macrocephala, and 6 parts of Perilla frutescens seed.

[0039] Compared with Example 1, this comparative example does not contain Rehmannia glutinosa or Adenophora stricta.

[0040] The preparation method of the composition is the same as in Example 1.

[0041] Comparative Example 4: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0042] Compared with Example 1, no cypress seed kernels or astragalus were added to the raw materials in this comparative example.

[0043] The preparation method of the composition is the same as in Example 1.

[0044] Comparative Example 5: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa seeds, 10 parts Platycladus orientalis seeds, and 8 parts Atractylodes macrocephala (fried).

[0045] Compared with Example 1, no Prunus japonica seeds, Astragalus membranaceus, or Perilla frutescens seeds were added to the raw materials in this comparative example.

[0046] The preparation method of the composition is the same as in Example 1.

[0047] Comparative Example 6: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Scrophularia ningpoensis, 10 parts Cannabis sativa seed, 8 parts Prunus japonica seed, 10 parts Platycladus orientalis seed, 9 parts Astragalus membranaceus, 8 parts stir-fried Atractylodes macrocephala, and 6 parts Perilla frutescens seed. Compared with Example 1, in this comparative example, Scrophularia ningpoensis is used instead of Adenophora stricta.

[0048] The preparation method of the composition is the same as in Example 1.

[0049] Comparative Example 7: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: Dendrobium 20 parts, Ophiopogon japonicus 12 parts, Scrophularia ningpoensis 13 parts, Cannabis sativa seed 10 parts, Prunus japonica seed 8 parts, Platycladus orientalis seed 10 parts, Astragalus membranaceus 9 parts, Atractylodes macrocephala (fried) 8 parts, Perilla frutescens seed 6 parts. Compared with Example 1, in this comparative example, Dendrobium substituted Rehmannia glutinosa.

[0050] The preparation method of the composition is the same as in Example 1.

[0051] Comparative Example 8: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Polygonatum odoratum, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts stir-fried Atractylodes macrocephala, and 6 parts Perilla frutescens. Compared with Example 1, this comparative example uses Polygonatum odoratum, which has similar efficacy, to replace Adenophora stricta.

[0052] The preparation method of the composition is the same as in Example 1.

[0053] Comparative Example 9: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: The ingredients are: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa seed, 9 parts Prunus japonica seed, 11 parts Trichosanthes kirilowii seed, 7 parts Astragalus membranaceus, 10 parts Atractylodes macrocephala, and 7 parts Perilla frutescens seed. The preparation steps of the composition are the same as in Example 1. Compared with Example 1, in this comparative example, Trichosanthes kirilowii seed (assistant herb) with similar efficacy is used to replace Platycladus orientalis seed, and Atractylodes macrocephala is used to replace Atractylodes macrocephala (adjuvant herb); at the same time, the raw material ratios of the assistant herbs (Prunus japonica seed and Trichosanthes kirilowii seed), adjuvant herbs (Astragalus membranaceus and Atractylodes macrocephala), and guiding herb (Perilla frutescens seed) are adjusted.

[0054] The preparation steps of the composition are the same as in Example 1.

[0055] Comparative Example 10: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 26 parts Rehmannia glutinosa, 17 parts Ophiopogon japonicus, 10 parts Cannabis sativa seed, 8 parts Prunus japonica seed, 10 parts Platycladus orientalis seed, 9 parts Astragalus membranaceus, 8 parts stir-fried Atractylodes macrocephala, and 6 parts Perilla frutescens seed.

[0056] Compared with Example 1, this comparative example did not include North American ginseng as a raw material, and the dosage of the auxiliary herbs Rehmannia glutinosa and Ophiopogon japonicus was increased.

[0057] The preparation method of the composition is the same as in Example 1.

[0058] Comparative Example 11: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 20 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0059] Compared with Example 1, the amount of North American ginseng used in this comparative example is increased.

[0060] The preparation method of the composition is the same as in Example 1.

[0061] Comparative Example 12: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 9 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0062] Compared with Example 1, the amount of North American ginseng used in this comparative example is reduced.

[0063] The preparation method of the composition is the same as in Example 1.

[0064] Comparative Example 13: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 10 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0065] Compared with Example 1, the amount of Rehmannia glutinosa used in this comparative example is reduced.

[0066] The preparation method of the composition is the same as in Example 1.

[0067] Comparative Example 14: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 30 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0068] Compared with Example 1, the amount of Rehmannia glutinosa used in this comparative example is increased.

[0069] The preparation method of the composition is the same as in Example 1.

[0070] Comparative Example 15: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 11 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0071] Compared with Example 1, the amount of Prunus japonica seed used in this comparative example is increased.

[0072] The preparation method of the composition is the same as in Example 1.

[0073] Comparative Example 16: A composition for treating constipation due to yin deficiency, comprising the following parts by weight: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 5 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

[0074] Compared with Example 1, the amount of Prunus japonica seed used in this comparative example is reduced.

[0075] The preparation method of the composition is the same as in Example 1.

[0076] Functional verification of the compositions prepared in Examples 1-3 and Comparative Examples 1-16: This experiment used a classic mouse model of blood and yin deficiency constipation. By detecting defecation function, intestinal motility function, yin deficiency-related oxidative stress, and intestinal aquaporin index, the therapeutic effect of the composition of the present invention on yin deficiency constipation was verified. At the same time, the effects of different missing, replaced, or abnormal dosages of medicinal ingredients on efficacy were compared.

[0077] Test Example 1: Bowel Function Indicator Test 1. Laboratory animals SPF-grade male ICR mice, weighing 25-30g, were purchased from Liaoning Changsheng Biotechnology Co., Ltd., Animal Production License No.: SCXK (Liaoning)-2015-0001.

[0078] The experimental mice were housed in an environment with a temperature of 22±1℃ and a humidity of 55%±10%, using a 12h / 12h light-dark alternation system with ample water and food, and a well-ventilated isolation cage system. Physical appearance, behavior, fecal characteristics, and diet were observed daily. Unfit animals were culled, and the mice were randomly assigned to groups of 10 each.

[0079] 2. Test substance: The dry extracts prepared in Examples 1-3 and Comparative Examples 1-16 were prepared into a suspension of 1 g crude drug / mL with 0.5% sodium carboxymethyl cellulose (CMC-Na) before use (3.0 g dry extract was added to every 100 mL suspension).

[0080] Positive control drug: Runchang Pills (National Drug Approval Number Z20023314), ground into powder before use, and prepared into a suspension of 1g crude drug / mL with 0.5% CMC-Na (100g Runchang Pills powder is added to every 100mL suspension).

[0081] 3. Modeling and testing reagents: Compound Reserpine Tablets (National Drug Approval Number H32026532), L-Thyroxine (National Drug Approval Number H20073700).

[0082] 4. Instruments: electronic balance, constant temperature drying oven, enzyme-linked immunosorbent assay (ELISA) reader, stereo microscope, high-speed centrifuge.

[0083] 5. Establishment of a mouse model of constipation due to yin deficiency Except for the blank control group, mice in the other groups were used to establish a Yin deficiency constipation model by gavage administration of compound reserpine and L-thyroxine: compound reserpine 0.3 mg / kg and L-thyroxine 0.8 mg / kg were administered by gavage once a day for 7 consecutive days. The blank control group was administered an equal volume of 0.5% CMC-Na by gavage daily. After the modeling was completed, the mice in the model groups showed typical symptoms of Yin deficiency constipation, such as dry stools, difficulty in defecation, reduced activity, and dry fur, indicating successful modeling.

[0084] 6. Dosage design and dosage After successful model establishment, drug administration was started and continued for 8 days, once a day, by gavage, with a drug volume of 10 mL / kg.

[0085] Blank control group and model control group: administered an equal volume of 0.5% CMC-Na by gavage; Positive control group: 1 g crude drug / mL of Runchang Pill suspension was administered by gavage, which is equivalent to 10 g / kg of raw medicinal material; Examples 1-3 and Comparative Examples 1-16: Gavage administration of a traditional Chinese medicine composition suspension corresponding to 1 g crude drug / mL, the dosage is equivalent to 10 g / kg of raw medicinal material; During the administration period, the mice were fed and hydrated normally, and their general condition was observed.

[0086] 7. Detection Method The time of first black feces, the number of fecal pellets in 6 hours, and the fecal water content were measured. After the end of day 6 of drug administration, mice were fasted but allowed free access to water for 12 hours. On day 7, 30 minutes after drug administration, mice in each group were administered 0.1 mL / 10 g of 10% charcoal suspension by gavage, while maintaining normal food and water intake. The time of first black feces excretion was recorded. All feces from mice within 6 hours were collected, and the number of fecal pellets was counted. The wet weight of the feces was measured, and the feces were dried in an 80℃ constant temperature drying oven for 12 hours until constant weight was achieved. The dry weight was measured, and the fecal water content was calculated using the formula. Fecal moisture content (%) = [(fecal wet weight - fecal dry weight) / fecal wet weight] × 100%.

[0087] 8. Test Results: Experimental measurement data are expressed as mean ± standard deviation (x̄ ± SD) and were processed using SPSS 26.0 statistical software. One-way ANOVA was used for comparisons of means among multiple groups. When variances were homogeneous, the LSD test was used for multiple comparisons; when variances were unequal, Dunnett's T3 test was used. P < 0.05 was considered statistically significant, and P < 0.01 was considered extremely statistically significant.

[0088] The results are shown in Table 1 and Figure 1-6 As shown.

[0089] Table 1. Results of defecation function indicators in each group of mice (x̄±SD, n=10)

[0090] Note: Compared with the blank control group, #P<0.05, ##P<0.01; compared with the model control group, *P<0.05, **P<0.01; compared with Example 1, △P>0.05, △△P<0.01.

[0091] Table 1 and Figure 1-6The results showed that Examples 1-3 significantly shortened the time to first black stool in mice, increased the number of fecal pellets at 6 hours, and increased fecal water content (P < 0.01), with no significant difference in efficacy among the three groups. Comparative Examples 1-16 showed significantly weaker defecation function improvement than Example 1 (P < 0.05 or P < 0.01). Comparative Example 3, lacking the principal herbs Rehmannia glutinosa and Adenophora stricta, showed the worst effect, only slightly improving fecal water content (P > 0.05), with no significant difference in the time to first black stool and the number of fecal pellets at 6 hours compared to the model group. Comparative Examples 6-9, with herb substitution, showed better efficacy than Comparative Examples 1-2, but significantly weaker than Example 1. Among the abnormal dosage groups (Comparative Examples 10-16), the greater the deviation from the range of this invention, the worse the efficacy. The overdose groups (Comparative Examples 10, 11, 14, and 15) were better than the reduced dosage groups (Comparative Examples 12, 13, and 16). It is evident that the compatibility and dosage ratio of the medicinal ingredients in the composition of this invention are scientific and precise. The synergistic effect among the medicinal ingredients is the key to its efficient improvement of defecation function in mice with yin deficiency and constipation. Any deviation from the compatibility or dosage of this invention will significantly weaken its efficacy.

[0092] Test Example 2: Detection of intestinal function indicators (charcoal propulsion rate, amplitude of contraction of isolated colonic smooth muscle) 1. Experimental animals, test substances, model establishment, and drug administration design: Same as test example 1.

[0093] 2. Test reagents: activated carbon powder (analytical grade), Tyrode's solution, and a mixture of 95% O2 and 5% CO2.

[0094] 3. Instruments: Ex vivo organ perfusion device, tension transducer, biosignal acquisition system, electronic balance, stereomicroscope.

[0095] 4. Detection method: (1) Carbon powder propulsion rate On day 8, 30 minutes after administration, mice in each group were administered 10 mL / kg of 10% charcoal powder suspension by gavage. Blood was collected from the orbital cavity 30 minutes later. Mice were euthanized by cervical dislocation, the mesentery was separated, and the small intestine (from the pylorus to the ileocecal junction) was removed. After being laid straight, the total length of the small intestine and the charcoal powder propulsion distance (distance from the pylorus to the leading edge of the charcoal powder) were measured. The charcoal powder propulsion rate was calculated using the formula: Charcoal powder propulsion rate (%) = [charcoal powder propulsion distance / total length of small intestine] × 100%.

[0096] (2) Amplitude of contraction of isolated colonic smooth muscle After euthanizing the mice, the colonic segment (about 2 cm) was quickly removed, rinsed in pre-cooled Tyrode's solution to remove contents, cut into 1 cm long segments, and suspended in an isolated organ perfusion device. The Tyrode's solution was kept at a constant temperature of 37°C and continuously oxygenated (95% O2 + 5% CO2). After equilibration for 30 min, the basic contraction amplitude of the colonic smooth muscle was recorded using a tension transducer, and the average contraction amplitude (mV) within 10 min was detected and recorded.

[0097] 5. Test results: The results are shown in Table 2.

[0098] Table 2 Results of intestinal function indicators in mice of each group (x̄±SD, n=10)

[0099] Note: Compared with the blank control group, #P<0.05, ##P<0.01; compared with the model control group, *P<0.05, **P<0.01; compared with Example 1, △P>0.05, △△P<0.01.

[0100] As shown in Table 2, Examples 1-3 significantly improved the charcoal propulsion rate and increased the contraction amplitude of isolated colonic smooth muscle in mice (P < 0.01), with better effects than the positive control group. Example 1 showed the best effect. There was no significant difference among Examples 1-3 (P > 0.05). The intestinal motility improvement effects of Comparative Examples 1-16 were significantly weaker than those of Example 1 (P < 0.05 or P < 0.01). The absence of the principal drug, the replacement of the core adjuvant drugs, and excessive or insufficient dosages all disrupted the original formula's drug compatibility balance, preventing the synergistic effect between the drugs and thus significantly reducing the intestinal motility improvement effect. Among them, Comparative Example 3 (lacking Rehmannia glutinosa and Adenophora stricta) showed no significant difference from the model group. (P>0.05) indicates that the core principal drug is the basis for the synergistic effect in the formulation. Without the principal drug, there is no synergistic effect, and the formulation cannot exert its efficacy in improving intestinal motility. The intestinal motility improvement effect of the drug missing group (Comparative Examples 1-5) was significantly worse than that of the drug replacement group (Comparative Examples 6-9) and the dosage abnormal group (Comparative Examples 10-16). This further proves that the yin-nourishing and fluid-increasing effect of the principal drug is the core of the intestinal motility recovery. Moreover, the synergistic effect formed by the principal drug and other drugs is the key to the effective improvement of intestinal function of the composition of the present invention. Even if only some adjuvant drugs are missing, the synergistic effect of the formulation will be greatly weakened, far less than the intestinal motility improvement effect of the original formulation.

[0101] Test Example 3: Detection of Yin Deficiency Related Indicators 1. The experimental animals, test substances, model establishment, and dosing design were the same as in Test Example 1. 2. The motilin (MTL) ELISA kit, vasoactive intestinal peptide (VIP) ELISA kit, superoxide dismutase (SOD) kit, and malondialdehyde (MDA) kit were all purchased from Nanjing Jiancheng Bioengineering Institute.

[0102] 3. Instruments ELISA reader, biological signal acquisition system.

[0103] 4. Detection Method (1) Detection of serum MTL and VIP levels Constipation is closely related to abnormal intestinal motility. Motilin (MTL) and vasoactive intestinal peptide (VIP) are core gastrointestinal hormones that regulate intestinal smooth muscle contraction and promote intestinal transmission (MTL promotes intestinal motility, while VIP inhibits intestinal motility). Therefore, detecting these indicators can reflect the status of intestinal motility. On day 8, 60 minutes after administration, blood was collected from the orbital cavity of mice, allowed to stand at room temperature for 30 minutes, and centrifuged at 3000 r / min for 10 minutes to separate the serum. The absorbance was measured on an enzyme-linked immunosorbent assay (ELISA) reader according to the instructions of the MTL and VIP kits, and the content of each indicator in the serum was calculated.

[0104] (2) Detection of serum SOD and MDA levels The core pathogenesis of constipation due to yin deficiency is the deficiency of yin fluid, and the state of yin deficiency is often accompanied by oxidative stress damage to the body (decreased SOD activity and increased MDA content). Therefore, the detection of SOD and MDA content can directly reflect the degree of repair of yin deficiency in the body. Follow the instructions for the SOD and MDA detection kits, measure the absorbance on an ELISA reader, and calculate the SOD activity (U / mL) and MDA content (nmol / mL) in the serum.

[0105] 5. Test results: The results are shown in Table 3.

[0106] Table 3. Results of serum marker detection in mice of each group (x̄±SD, n=10)

[0107] Note: Compared with the blank control group, #P<0.05, ##P<0.01; compared with the model control group, *P<0.05, **P<0.01; compared with Example 1, △P>0.05, △△P<0.01.

[0108] As shown in Table 3, the model group mice exhibited gastrointestinal hormone disorders (decreased MTL, increased VIP) and oxidative stress damage (decreased SOD, increased MDA). Examples 1-3 significantly upregulated serum MTL levels, significantly downregulated VIP levels (P < 0.01), significantly increased SOD activity, and significantly decreased MDA levels (P < 0.01). All indicators recovered to levels close to the blank control group. Example 1 showed the best effect, and there was no significant difference among the Example 1-3 groups (P > 0.05). The regulatory effects of all comparative examples on the above indicators were significantly weaker than those of Example 1 (P < 0.05 or P < 0.01). Among them, Comparative Example 3 (lacking the principal herbs Rehmannia glutinosa and Adenophora stricta) had almost no regulatory effect on each indicator and was not significantly different from the model group (P > 0.05). Although the herb substitution groups of Comparative Examples 6-9 could regulate each indicator to a certain extent, the effect was far less than that of Examples 1-3, indicating that the medicinal properties and efficacy of the principal herbs Adenophora stricta and Rehmannia glutinosa cannot be replaced by other yin-nourishing herbs. In the abnormal dosage groups (too low or too high) of Comparative Examples 10-16, the greater the deviation of the raw material dosage from the range defined by the present invention, the worse the indicator regulation effect. The improvement effect of the reduced dosage group was significantly weaker than that of the excessive dosage group, further verifying that the weight ratio defined by the present invention is the optimal ratio.

[0109] The above results demonstrate that the composition of this invention can improve constipation due to yin deficiency by addressing intestinal motility and yin deficiency. The composition and dosage of this invention are optimally selected. Furthermore, it indicates that the medicinal ingredients and their proportions in this invention are not conventionally chosen; there is a significant synergistic effect between the various medicinal ingredients, and a remarkable effect is achieved through specific compatibility.

[0110] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A composition for treating yin deficiency constipation, characterized by, The composition consists of the following raw materials: Rehmannia glutinosa, Ophiopogon japonicus, Adenophora stricta, Cannabis sativa seed, Prunus japonica seed, Platycladus orientalis seed, Astragalus membranaceus, Atractylodes macrocephala (fried), and Perilla frutescens seed.

2. The composition for treating yin deficiency constipation according to claim 1, characterized in that, The raw materials of the composition are formulated in the following weight proportions: 15-25 parts of Rehmannia glutinosa, 10-15 parts of Ophiopogon japonicus, 10-15 parts of Adenophora stricta, 8-12 parts of Cannabis sativa seed, 6-10 parts of Prunus japonica seed, 8-12 parts of Platycladus orientalis seed, 6-12 parts of Astragalus membranaceus, 6-10 parts of Atractylodes macrocephala (fried), and 5-8 parts of Perilla frutescens seed.

3. The composition for treating yin deficiency constipation according to claim 2, characterized in that, The raw materials of the composition are formulated in the following weight proportions: 20 parts Rehmannia glutinosa, 12 parts Ophiopogon japonicus, 13 parts Adenophora stricta, 10 parts Cannabis sativa, 8 parts Prunus japonica, 10 parts Platycladus orientalis, 9 parts Astragalus membranaceus, 8 parts Atractylodes macrocephala (fried), and 6 parts Perilla frutescens.

4. The method for preparing the composition for treating constipation due to yin deficiency according to claim 1, characterized in that, Includes the following steps: Weigh the pulverized raw materials, add water, soak them, and then decoct them twice. Combine the filtrates from the second decoction and concentrate them to obtain the composition.

5. The method for preparing the composition for treating constipation due to yin deficiency according to claim 4, characterized in that, The preparation method is specifically as follows: Weigh the pulverized raw material, add 10 times the volume of water to the raw material, soak for 1 hour, heat to boiling, continue to simmer for 30 minutes, filter, add 10 times the volume of water to the filtered residue and simmer for 30 minutes, filter, combine the filtrates, concentrate to a crude drug equivalent of 0.2 g / mL, and obtain the extract of the composition.

6. The method for preparing the composition for treating constipation due to yin deficiency according to claim 5, characterized in that, The decoction temperature is 90-100℃, and a gentle boil is maintained during the decoction process, with stirring every 10 minutes; the filtration uses a 100-200 mesh filter to remove the dregs and impurities.

7. Use of the composition for treating constipation due to yin deficiency according to any one of claims 1-3 in the preparation of a medicine having a laxative function.

8. The use according to claim 7, characterized in that, The dosage form of the medicine is tablets, powders, capsules, decoctions, granules, or pills.

9. The use of the composition for treating constipation due to yin deficiency according to any one of claims 1-3 in the preparation of a medicine for treating constipation due to yin deficiency and intestinal dryness in the elderly, constipation due to yin deficiency after childbirth, or constipation due to yin deficiency after radiotherapy and chemotherapy.

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