A pharmaceutical composition for treating insomnia combined with senile nocturia, its preparation and application

Abstract

The application discloses a kind of drug composition and preparation and application for treating insomnia combined with senile nocturia.The composition is composed of 15-20 parts of hamamelis virginiana, 15-20 parts of officinal cinnamon, 10-15 parts of lily, 15-20 parts of ganoderma lucidum, 8-15 parts of cloud fruit, 7-10 parts of eel, 7-10 parts of mountain gardenia tea, 7-10 parts of water calamus, 3-5 parts of jujube, and the preparation method is as follows: the above-mentioned medicinal materials are mixed, crushed, added with water and cellulase, and then extracted under certain temperature and PH conditions; after heating and boiling, filtration is carried out; the residue after filtration is added with water and heated to decoct, filtration is carried out, and then the water decoction and enzyme-extracted liquid are combined, concentrated to thick paste, and then added with appropriate amount of excipient for batching to prepare corresponding dosage form, thereby obtaining the product.The prepared product has the effects of tonifying kidney and discharging fire, and communicating heart and kidney, and can be used for treating insomnia combined with senile nocturia caused by heart-kidney disharmony, and has remarkable treatment effect, no obvious side effect and no adverse reaction.

Description

Technical Field

[0001] This invention relates to the field of medicine, specifically to a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly, its preparation method, and its application. Background Technology

[0002] Insomnia, also known as sleep continuity disorder, is a common experience of difficulty sleeping. It refers to the inability to obtain satisfactory sleep duration and quality even under suitable sleep conditions, and can even affect daytime social functioning. It is often accompanied by daytime fatigue, headaches and body aches, mood disorders (such as depression and anxiety), and cognitive impairment. The pathological mechanisms of insomnia involve a wide range of brain regions, including the hippocampus, hypothalamus, and prefrontal cortex. These regions, as components of the limbic-cortical system, are closely related to cognitive function. Chronic insomnia can also increase the risk of substance abuse, suicide, traffic accidents, and may even lead to immune dysfunction. Up to one-third of adults worldwide suffer from insomnia, making it a significant factor affecting people's health and quality of life.

[0003] Currently, the clinical treatment of insomnia mainly includes three methods: traditional Chinese medicine (TCM), sedative-hypnotic drugs, and cognitive behavioral therapy (CBT). CBT for insomnia is not widely used in China due to its long treatment cycle, slow onset of action, and high cost. While sedative-hypnotic drugs have a faster onset of action and are convenient to use, they may also cause a series of adverse reactions such as drowsiness, delirium, behavioral disorders, and drug addiction. TCM has a long history and rich practical experience in treating insomnia, dating back to the diagnosis and treatment of "restless sleep" and "inability to close the eyes" in the *Huangdi Neijing* (Yellow Emperor's Inner Classic). Many other TCM classics have also recorded classic prescriptions for treating insomnia. TCM treatment of insomnia is widely used in China due to its unique advantages (such as synergistic effects of multiple components and targets, stable efficacy, few adverse reactions, and low recurrence rate). TCM prescriptions have also been proven by evidence-based medicine to have good sedative and hypnotic effects.

[0004] Clinically, insomnia is classified into four subtypes based on symptoms: difficulty falling asleep, difficulty maintaining sleep, early awakening, or a combination of these three. The psychological factors influencing these subtypes differ. Traditional Chinese medicine (TCM) categorizes insomnia into nine syndrome types based on its pathogenesis: Type 1: Liver Qi Stagnation Transforming into Fire. Impaired liver function leads to Qi stagnation, which in turn transforms into fire. This fire rises upwards, disturbing the heart and causing restlessness and insomnia. Type 2: Yin Deficiency with Hyperactive Fire. Yin deficiency results in insufficient body fluids, leaving Yang Qi unchecked. This leads to excessive Yang generating heat, which transforms into deficiency fire, causing an imbalance of Yang Qi and resulting in heat disturbing the mind and causing insomnia. Type 3: Phlegm-Heat Disturbance. Improper diet leads to food stagnation in the spleen and stomach, causing phlegm-heat to accumulate and obstruct the heart orifices, resulting in insomnia. Type 4: Heart-Kidney Disharmony. The kidneys govern water, and kidney water, propelled by kidney yang, ascends to nourish the heart and interacts with heart fire, forming a harmonious balance of water and fire. If kidney water or kidney yang is insufficient, the heart and kidneys fail to communicate, leading to insomnia. The fifth category is deficiency of both the heart and spleen. The spleen governs transformation and transportation; spleen deficiency weakens its function, resulting in insufficient qi and blood to nourish the heart, causing insomnia. The sixth category is deficiency of heart and gallbladder qi. Deficiency of heart and gallbladder qi easily leads to palpitations, shortness of breath, constant anxiety, frequent awakenings at night, easy startling, timidity, and fear. The seventh category is disharmony of stomach qi. The saying "If the stomach is not in harmony, one cannot sleep peacefully" reflects this. Dietary imbalances lead to liver qi stagnation and stomach qi disharmony, obstructing the ascending and descending of qi, making it difficult to sleep soundly. The eighth category is excessive heart fire. Those with excessive heart fire often experience restlessness, insomnia, five-center heat (heat in the palms, soles, and chest), dizziness, tinnitus, mouth ulcers, dry mouth, lower back pain, nocturnal emission, and spermatorrhea. The ninth category is internal obstruction of blood stasis. If there is blood stasis in the body that obstructs the blood vessels, the qi and blood cannot nourish the mind and spirit. If the mind cannot store the spirit and the blood vessels cannot hold the spirit, then one will not be able to sleep.

[0005] This invention provides a pharmaceutical composition for treating insomnia due to heart-kidney disharmony complicated with nocturia in the elderly. The composition consists of nine herbs: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Eriobotrya scabra, Gardenia jasminoides, Acorus calamus, and Ziziphus jujuba.

[0006] Mahonia bealei (Fort.) Carr. or Mahonia fortuneei (Lindl.) Fedde, both belonging to the Berberidaceae family, are dried stems. They are bitter and cold in nature. They enter the liver, stomach, and large intestine meridians. They have the functions of clearing heat and drying dampness, purging fire and detoxifying. They are used for damp-heat diarrhea, jaundice with red urine, red and swollen eyes, toothache due to stomach fire, and boils and carbuncles.

[0007] Cinnamon bark is the dried bark of *Cinnamomum cassia* Presl., a plant in the Lauraceae family. It has a pungent and sweet taste and is very hot in nature. It enters the kidney, spleen, heart, and liver meridians. It has the functions of tonifying fire and assisting yang, guiding fire back to its source, dispelling cold and relieving pain, and warming and unblocking the meridians. It is used for impotence and cold uterus, cold pain in the lower back and knees, kidney deficiency causing shortness of breath, upward floating of deficient yang, dizziness and red eyes, cold pain in the heart and abdomen, vomiting and diarrhea due to deficiency and cold, abdominal pain due to cold hernia, dysmenorrhea, and amenorrhea.

[0008] Mountain lily refers to the dried, fleshy scales of the plant *Lilium davidii* Duch, belonging to the Liliaceae family. It has a sweet and slightly bitter taste, and is slightly cold in nature. It enters the heart, lung, and intestinal meridians. It has the effects of nourishing yin and moistening the lungs, clearing the heart and calming the mind. It is used for yin deficiency with chronic cough, insomnia, and excessive dreaming.

[0009] Reishi mushroom is the dried fruiting body of the fungus *Ganoderma lucidum* (family Ganodermataceae). It has a bitter taste and neutral properties. It enters the heart, liver, lung, and kidney meridians. It benefits heart qi, invigorates blood circulation, strengthens the heart vessels, and calms the mind; it is used for insomnia, depression, and neurasthenia.

[0010] Caesalpinia decapetala (Roth) Alston, a legume, is a dried flower. It has a sweet taste and neutral properties. It enters the spleen and kidney meridians. It has the effects of tonifying qi and strengthening the spleen, nourishing yin and benefiting the kidneys. It is used for spleen and stomach weakness, fatigue, and insufficient essence and blood.

[0011] Eel refers to the meat or whole body of the yellow eel (Monopterus albus (Zuiew), a species of eel belonging to the Synbranchidae family. It has a sweet taste and warm nature. It enters the liver, spleen, and kidney meridians. It has the effects of nourishing qi and blood, tonifying the liver and kidneys, and strengthening muscles and bones. It is used for general weakness, malnutrition, lower back pain, and impotence.

[0012] Gardenia tea is made from the dried roots and stems of Pittosporum glabratum Lindl., a plant in the Pittosporum family. It has a bitter and astringent taste and is neutral in nature. It possesses the effects of dispelling wind and dampness, calming the mind and soothing the nerves, and promoting blood circulation. It is used for rheumatic pain, insomnia, dreaminess, lower back pain, and leg pain.

[0013] Sweet flag (Acorus calamus L.) is the dried rhizome of the plant, belonging to the Araceae family. It has a pungent and bitter taste, and is slightly warm in nature. It enters the liver, stomach, and heart meridians. It has the effects of resolving phlegm and opening the orifices, resolving dampness and strengthening the stomach. It is used for phlegm-induced coma, palpitations and forgetfulness, tinnitus and deafness, etc.

[0014] Jujube is the dried, ripe fruit of the plant Ziziphus jujuba Mill., belonging to the Rhamnaceae family. It has a sweet taste and warm properties. It enters the spleen, stomach, and heart meridians. It has the effects of tonifying the middle energizer and replenishing qi, nourishing blood and calming the mind. It is used for spleen deficiency with poor appetite, fatigue, loose stools, and hysteria in women.

[0015] In this formula, *Mahonia japonica* (Gong Lao Mu) is cold in nature, clearing heat and drying dampness, purging fire and detoxifying; *Cinnamomum cassia* (Guan Gui) is hot in nature, tonifying fire and assisting yang, guiding fire back to its source. The combination of these two herbs balances their cold and hot properties, promotes ascending and descending functions, harmonizes the heart and kidneys, and achieves a balance of water and fire, thus serving as the principal herbs. *Lilium brownii* (Shan Bai He) calms the mind and soothes the nerves; *Ganoderma lucidum* (Ling Zhi) benefits the heart qi, invigorates the heart blood, and assists the heart and Chong meridians; *Fructus buergerianum* (Yun Shi Hua) tonifies qi and strengthens the spleen, nourishes yin and benefits the kidneys; *Eel* (Shan Yu) benefits qi and blood, tonifies the liver and kidneys, and enhances the calming and kidney-tonifying effects of the principal herbs, thus serving as the assistant herbs. *Gardenia jasminoides* (Shan Zhi Cha) is added to calm the mind and soothe the nerves, invigorate blood and unblock the meridians; *Acorus calamus* (Shui Chang Pu) opens the orifices and resolves phlegm. Finally, jujube (Da Zao) is added to harmonize the other herbs as the guiding herb. The entire formula works to tonify the kidneys, clear heat, and harmonize the heart and kidneys. It is used to treat insomnia complicated by nocturia in the elderly caused by disharmony between the heart and kidneys.

[0016] This composition has been used clinically for a long time, with a total effective rate of over 90% in treating insomnia due to heart-kidney disharmony combined with nocturia in the elderly, demonstrating significant efficacy. Clinically, it is decocted in water, indicating that the water-soluble components are a crucial material basis for the composition's therapeutic effect. However, literature review shows that the alcohol-soluble components in this composition can also play a role in treating insomnia. Therefore, if a preparation method can be found to extract and combine the water-soluble and alcohol-soluble components of this invention's composition, the clinical dosage can be reduced, saving a significant amount of valuable traditional Chinese medicine resources. Summary of the Invention

[0017] The purpose of this invention is to provide a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly.

[0018] Another object of the present invention is to provide a method for preparing a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly.

[0019] Another object of the present invention is to provide a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly, and its use in a pharmaceutical preparation for treating insomnia complicated with nocturia in the elderly caused by heart-kidney disharmony.

[0020] To address the challenge of low extraction rates of alcohol-soluble alkaloids in drug compositions for treating insomnia combined with nocturia in the elderly, this invention first extracts the medicinal materials in the prescription through enzymatic hydrolysis, and then decocts the residue in water to extract the remaining ingredients.

[0021] This invention is achieved through the following technical solution:

[0022] The present invention discloses a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly, which is composed of the following raw materials in parts by weight: 15-20 parts of Mahonia fortunei, 15-20 parts of Cinnamomum cassia, 10-15 parts of Lilium brownii, 15-20 parts of Ganoderma lucidum, 8-15 parts of Eriocaulon buergerianum, 7-10 parts of Eel, 7-10 parts of Gardenia jasminoides, 7-10 parts of Acorus calamus, and 3-5 parts of Ziziphus jujuba.

[0023] Preferably, the pharmaceutical composition of the present invention is composed of the following raw material components in parts by weight: 15-17 parts of Mahonia fortunei, 15-17 parts of Cinnamomum cassia, 10-12 parts of Lilium brownii, 15-17 parts of Ganoderma lucidum, 8-11 parts of Eriocaulon buergerianum, 7-9 parts of Eriocaulon buergerianum, 7-9 parts of Gardenia jasminoides, 7-9 parts of Acorus calamus, and 3-4 parts of Ziziphus jujuba.

[0024] More preferably, the pharmaceutical composition of the present invention is composed of the following raw material components in parts by weight: 15 parts of Mahonia fortunei, 15 parts of Cinnamomum cassia, 10 parts of Lilium brownii, 15 parts of Ganoderma lucidum, 8 parts of Eriocaulon buergerianum, 7 parts of Eriocaulon buergerianum, 7 parts of Gardenia jasminoides tea, 7 parts of Acorus calamus, and 3 parts of Ziziphus jujuba.

[0025] The present invention discloses a method for preparing a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly, comprising the following steps:

[0026] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the formula ratio: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0027] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0028] (3) Enzymatic extraction: Add 6-10 times the amount of water of the medicinal materials, and then add 1.0-3.0% of cellulase. Soak at 50℃ and pH 5.0 for 24-48 hours. After boiling for 10-30 minutes, filter to obtain the enzymatic extract.

[0029] (4) Decoction: Add the remaining dregs after filtration in step (3) to 4-8 times the total amount of the medicinal materials in water, heat and decoct for 15-45 minutes, filter, and obtain the decoction.

[0030] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0031] (6) Prepare the corresponding dosage form by adding pharmaceutically acceptable excipients to the thick paste to prepare the corresponding dosage form.

[0032] Preferably, the enzymatic extraction in step (3) of the present invention is as follows: add 8 times the amount of water of the medicinal materials, add 1.5% cellulase, soak for 36 hours at 50°C and pH 5.0, heat and boil for 30 minutes and then filter to obtain the enzymatic extract.

[0033] Preferably, the decoction in step (4) of the present invention is as follows: add the remaining dregs after filtration in step (3) to 6 times the total amount of water of the medicinal materials, heat and decoct for 30 minutes, filter, and obtain the decoction.

[0034] The application of the pharmaceutical composition for treating insomnia complicated with nocturia in the elderly, or the thick paste prepared by the method for treating insomnia complicated with nocturia in the elderly, in the preparation of pharmaceutical formulations for treating insomnia complicated with nocturia in the elderly caused by heart-kidney disharmony.

[0035] The pharmaceutical preparation of the present invention comprises the pharmaceutical composition for treating insomnia combined with nocturia in the elderly or a thick paste prepared by the method for treating insomnia combined with nocturia in the elderly and pharmaceutically acceptable excipients.

[0036] The pharmaceutical preparations described in this invention are solid or liquid preparations.

[0037] The solid dosage forms of this invention are granules, capsules, tablets, and pills; the liquid dosage forms are oral liquids.

[0038] The weight units mentioned in this invention can be g, kg, or other weight units known in the pharmaceutical field.

[0039] Compared with the prior art, the present invention has the following advantages:

[0040] 1. Significant therapeutic effect. Clinical efficacy trial results show that the preparation made from the pharmaceutical composition of this invention, when used in combination with Western medicine, can improve the therapeutic effect of insomnia combined with nocturia in the elderly, with a total effective rate of 88.0%. This is significantly different from the total effective rate of 66.0% in the control group that used Western medicine alone, indicating that this invention can effectively improve patients' clinical symptoms and enhance their quality of life.

[0041] 2. The preparation method of this invention is stable and feasible. Through extraction method, single-factor experiment investigation and optimal extraction process verification, the results are as follows: (1) The contents of various effective components (total alkaloids, total flavonoids and total polysaccharides) in the enzymatic hydrolysis decoction method are as follows: total alkaloids 19.40 mg / g, total flavonoids 8.22 mg / g and total polysaccharides 53.83 mg / g, which are significantly better than the traditional water extraction method; (2) The optimal extraction process parameters of the enzymatic hydrolysis decoction method are: using 2.0% cellulase, soaking at 50℃ and pH 5.0 for 36 h, boiling for 15 min and then filtering; adding 8 times the amount of water of the medicinal material to the residue, heating and decoct for 15 min and filtering. Under the optimal extraction process conditions, the contents of each effective component are high; (3) The optimal extraction process conditions have been verified. The average content of total alkaloids is 20.05 mg / g, the average content of total flavonoids is 9.49 mg / g and the average content of total polysaccharides is 55.38 mg / g, indicating that the extraction process has good repeatability and is reasonable and feasible.

[0042] 3. The preparation method of this invention improves the extraction rate of the active ingredients in the composition. The original method of using the composition of this invention was the traditional water extraction method, i.e., boiling in water. The dry extract prepared by this method contained 3.24 mg / g of total flavonoids, 8.42 mg / g of total alkaloids, and 22.87 mg / g of total polysaccharides. After improvement by the team of this invention, an enzymatic hydrolysis water decoction method was used to extract the composition. As a result, the dry extract contained 9.49 mg / g of total flavonoids, 20.05 mg / g of total alkaloids, and 55.38 mg / g of total polysaccharides. The contents of the three active ingredients were all doubled, enriching both alcohol-soluble and water-soluble active ingredients.

[0043] 4. Reduced dosage of the drug composition. Clinical efficacy trial results showed that after the original clinical dosage of medicinal materials was prepared by fermentation and decoction, the total effective rate reached 84.0%, which fully demonstrates that the extraction of the composition by fermentation and decoction halved the amount of medicinal materials used, effectively saving Chinese medicinal resources.

[0044] 5. The composition of the present invention is more convenient to use after being formulated into a preparation. When the pharmaceutical composition of the present invention is formulated into a preparation (granules, capsules, etc.), it is more convenient for patients to take, carry, and store compared to decoction.

[0045] 6. The product prepared by this invention is safe, with no obvious side effects or adverse reactions. Detailed Implementation

[0046] The technical solution of the present invention will be further described in detail below through specific embodiments.

[0047] Example 1: A pharmaceutical composition for treating insomnia complicated with nocturia in the elderly.

[0048] Composition: 450g Mahonia japonica, 450g Cinnamomum cassia, 300g Lilium brownii, 450g Ganoderma lucidum, 240g Eriocaulon buergerianum, 210g Eel, 210g Gardenia jasminoides, 210g Acorus calamus, 90g Jujube.

[0049] Example 2: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0050] Ingredients: 400g Mahonia japonica, 500g Cinnamomum cassia, 450g Lilium brownii, 400g Ganoderma lucidum, 300g Eriocaulon buergerianum, 250g Eel, 220g Gardenia jasminoides, 200g Acorus calamus, 100g Jujube.

[0051] Example 3: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0052] Ingredients: 300g Mahonia japonica, 300g Cinnamomum cassia, 250g Lilium brownii, 200g Ganoderma lucidum, 150g Eriocaulon buergerianum, 120g Eel, 120g Gardenia jasminoides, 100g Acorus calamus, 70g Jujube.

[0053] Example 4: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0054] Ingredients: 350g Mahonia japonica, 400g Cinnamomum cassia, 300g Lilium brownii, 250g Ganoderma lucidum, 180g Eel, 100g Gardenia jasminoides, 150g Acorus calamus, 120g Jujube.

[0055] Example 5: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0056] Ingredients: 500g Mahonia japonica, 400g Cinnamomum cassia, 350g Lilium brownii, 400g Ganoderma lucidum, 240g Eel, 210g Gardenia jasminoides, 210g Acorus calamus, 80g Jujube.

[0057] Example 6: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0058] Composition: 400g of Mahonia japonica, 350g of Cinnamomum cassia, 300g of Lilium brownii, 300g of Ganoderma lucidum, 150g of Prunus mume, 100g of eel, 150g of Gardenia jasminoides, 120g of Acorus calamus, and 80g of jujube.

[0059] Example 7: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0060] Ingredients: 300g Mahonia japonica, 300g Cinnamomum cassia, 250g Lilium brownii, 250g Ganoderma lucidum, 150g Eel, 120g Gardenia jasminoides, 100g Acorus calamus, 60g Jujube.

[0061] Example 8: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0062] Ingredients: 400g Mahonia japonica, 400g Cinnamomum cassia, 300g Lilium brownii, 400g Ganoderma lucidum, 240g Eel, 200g Gardenia jasminoides tea, 200g Acorus calamus, 80g Jujube.

[0063] Example 9: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0064] Ingredients: 340g Mahonia japonica, 340g Cinnamomum cassia, 240g Lilium brownii, 340g Ganoderma lucidum, 220g Eel, 180g Gardenia jasminoides, 180g Acorus calamus, 80g Jujube.

[0065] Example 10: Pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0066] Composition: 340g Mahonia japonica, 300g Cinnamomum cassia, 200g Lilium brownii, 300g Ganoderma lucidum, 160g Eriocaulon buergerianum, 180g Eel, 140g Gardenia jasminoides, 140g Acorus calamus, 60g Jujube.

[0067] The composition of the traditional Chinese medicine composition in Examples 1-10 was used in the preparation methods of the following examples.

[0068] Example 11: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0069] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0070] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0071] (3) Enzymatic extraction: Add 8 times the amount of water to the coarsest powder of medicinal materials, and then add 1.5% cellulase. Soak for 36 h at 50℃ and pH 5.0. After boiling for 30 min, filter to obtain the enzymatic extract.

[0072] (4) Decoction: Add the remaining dregs after filtration in step (3) to 6 times the total amount of water of the medicinal materials, heat and decoct for 30 minutes, filter, and obtain the decoction.

[0073] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0074] (6) Prepare the corresponding dosage form by adding 250g of microcrystalline cellulose, 5g of aspartame and an appropriate amount of soluble starch to the thick paste, mix evenly, granulate through an 18-mesh sieve, dry at 70℃, and granulate to make 1000g of granules, which is the granule.

[0075] Example 12: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0076] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0077] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0078] (3) Enzymatic extraction: Add 10 times the amount of water to the coarsest powder of medicinal materials, and then add 1.0% cellulase. Soak for 48 h at 50℃ and pH 5.0. After boiling for 20 min, filter to obtain the enzymatic extract.

[0079] (4) Decoction: Add the remaining dregs after filtration in step (3) to 8 times the total amount of water of the medicinal materials, heat and decoct for 20 minutes, filter, and obtain the decoction.

[0080] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0081] (6) Prepare the corresponding dosage form by adding 400g of microcrystalline cellulose, 10g of aspartame and an appropriate amount of soluble starch to the thick paste, mix evenly, granulate through an 18-mesh sieve, dry at 70℃, and granulate to make 1000g of granules, which is the granule.

[0082] Example 13: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0083] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0084] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0085] (3) Enzymatic extraction: Add 6 times the amount of water to the coarsest powder, then add 2.0% cellulase, and extract for 24 h at 50℃ and pH 5.0. After boiling for 20 min, filter to obtain the enzymatic extract.

[0086] (4) Decoction: Add the remaining dregs after filtration in step (3) to 4 times the total amount of water of the medicinal materials, heat and decoct for 45 minutes, filter, and obtain the decoction.

[0087] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0088] (6) Prepare the corresponding dosage form by adding 200g of soluble starch to the thick paste, mix evenly, dry, pulverize, add 5g of magnesium stearate, mix evenly, fill into capsule shells, and obtain 1000 capsules, which is the capsule preparation.

[0089] Example 14: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0090] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0091] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0092] (3) Enzymatic extraction: Add 8 times the amount of water to the coarsest powder, then add 3.0% cellulase, and extract for 36 h at 50℃ and pH 5.0. After boiling for 30 min, filter to obtain the enzymatic extract.

[0093] (4) Decoction: Add the remaining dregs after filtration in step (3) to 6 times the total amount of water of the medicinal materials, heat and decoct for 15 minutes, filter, and obtain the decoction.

[0094] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0095] (6) Prepare the corresponding dosage form by adding 100g of soluble starch to the thick paste, mix evenly, dry, pulverize into fine powder, add 5g of sodium carboxymethyl starch, and make 1000 pills with 10g of refined honey.

[0096] Example 15: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0097] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0098] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0099] (3) Enzymatic extraction: Add 8 times the amount of water to the coarsest powder of medicinal materials, and then add 1.5% cellulase. Soak for 36 h at 50℃ and pH 5.0. After boiling for 30 min, filter to obtain the enzymatic extract.

[0100] (4) Decoction: Add the remaining dregs after filtration in step (3) to 6 times the total amount of water of the medicinal materials, heat and decoct for 30 minutes, filter, and obtain the decoction.

[0101] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0102] (6) Prepare the ingredients into the corresponding dosage form: Add an appropriate amount of starch and dextrin to the thick paste, compress into tablets, and make 1000g tablets to obtain tablets.

[0103] Example 16: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0104] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0105] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0106] (3) Enzymatic extraction: Add 8 times the amount of water to the coarsest powder, then add 2.0% cellulase, and extract at 50℃ and pH 5.0 for 48 h. After boiling for 30 min, filter to obtain the enzymatic extract.

[0107] (4) Decoction: Add the remaining dregs after filtering in step (3) to 8 times the total amount of water of the medicinal materials, heat and decoct for 30 minutes, filter, and obtain the decoction.

[0108] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0109] (6) Prepare the ingredients into the corresponding dosage form: Add an appropriate amount of starch and dextrin to the thick paste, compress into tablets, and make 1000g tablets to obtain tablets.

[0110] Example 17: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0111] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0112] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0113] (3) Enzymatic extraction: Add 8 times the amount of water to the coarsest powder of medicinal materials, and then add 1.5% cellulase. Soak for 36 h at 50℃ and pH 5.0. After boiling for 30 min, filter to obtain the enzymatic extract.

[0114] (4) Decoction: Add the remaining dregs after filtration in step (3) to 6 times the total amount of water of the medicinal materials, heat and decoct for 30 minutes, filter, and obtain the decoction.

[0115] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0116] (6) Prepare the ingredients into the corresponding dosage form: dilute the thick paste with water, add 20g of sodium benzoate, stir and mix thoroughly, and then adjust the volume to 1000mL to obtain the oral liquid.

[0117] Example 18: Preparation of a pharmaceutical composition for treating insomnia complicated with nocturia in the elderly

[0118] (1) Weigh the medicinal materials: Weigh out the following ingredients according to the prescription: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Jujube;

[0119] (2) Coarse grinding of medicinal materials: Mix all the medicinal materials in step (1) and grind them into the coarsest powder that passes through 10 mesh;

[0120] (3) Enzymatic extraction: Add 10 times the amount of water to the coarsest powder of medicinal materials, then add 2.0% cellulase, and extract at 50℃ and pH 5.0 for 48 h. After heating and boiling for 20 min, filter to obtain the enzymatic extract.

[0121] (4) Decoction: Add the remaining dregs after filtration in step (3) to 8 times the total amount of water of the medicinal materials, heat and decoct for 20 minutes, filter, and obtain the decoction.

[0122] (5) Concentration: Combine the decoction and the enzymatic extract and concentrate them into a thick paste;

[0123] (6) Prepare the ingredients into the corresponding dosage form: dilute the thick paste with water, add 40g of sodium benzoate, stir and mix thoroughly, and then adjust the volume to 1000mL to obtain the oral liquid.

[0124] To further verify the feasibility of the present invention, the inventors conducted a series of experiments, as follows:

[0125] I. Optimization Experiment of Preparation Process

[0126] This invention's prescription consists of nine ingredients: Mahonia japonica, Cinnamomum cassia, Lilium brownii, Ganoderma lucidum, Eriobotrya japonica, Gardenia jasminoides, Acorus calamus, and Ziziphus jujuba. Research indicates that the main active ingredients in Mahonia japonica, Lilium brownii, and Gardenia jasminoides are alkaloids; the main active ingredients in Ganoderma lucidum and Ziziphus jujuba are polysaccharides; and the main active ingredients in Cinnamomum cassia, Eriobotrya japonica, and Acorus calamus are flavonoids. The original method of using this prescription was the traditional water extraction method, which involves decocting the herbs in water. This method is insufficient to extract alcohol-soluble alkaloids and other alkaloid-like active ingredients, hindering the maximization of the medicinal effects and inevitably wasting medicinal resources. To find the optimal extraction method, the invention team used the content of alkaloids, polysaccharides, and flavonoids in the extract as evaluation indicators. Through experiments, they compared five different extraction processes: water extraction, alcohol extraction, alcohol-water dual extraction, enzymatic hydrolysis, and enzymatic hydrolysis-water decoction, ultimately selecting the optimal extraction process.

[0127] 1. Initial selection of extraction methods

[0128] (1) Water extraction method

[0129] The medicinal materials (15g of Mahonia japonica, 15g of Cinnamomum cassia, 10g of Lilium brownii, 15g of Ganoderma lucidum, 8g of Eriobotrya japonica, 7g of Eriobotrya japonica, 7g of Gardenia jasminoides, 7g of Acorus calamus, and 3g of Ziziphus jujuba) were weighed according to the formula ratio. After coarse pulverization, 10 times the amount of water was added, and the mixture was heated and extracted twice, each time for 0.5 hours. The mixture was filtered, the filtrate was concentrated and diluted to an appropriate volume, and the contents of alkaloids, polysaccharides and flavonoids were determined. The results are shown in Table 1.

[0130] (2) Alcohol extraction method

[0131] The medicinal materials were weighed according to the formula ratio, coarsely pulverized, and then 10 times the amount of 60% ethanol was added. The mixture was heated and extracted twice, each time for 0.5 hours. After filtration, the ethanol was recovered from the filtrate, and the solution was concentrated and diluted to an appropriate volume. The contents of alkaloids, polysaccharides and flavonoids were determined. The results are shown in Table 1.

[0132] (3) Alcohol-water dual extraction method

[0133] Weigh the medicinal materials according to the formula ratio, coarsely grind them, add 10 times the amount of 60% ethanol, heat and extract for 0.5 hours, filter, recover the ethanol from the filtrate to obtain the ethanol extract, add 10 times the amount of water to the residue, heat and extract for 0.5 hours, filter, combine the filtrate with the above ethanol extract, concentrate and make up to an appropriate volume, and determine the contents of alkaloids, polysaccharides and flavonoids. The results are shown in Table 1.

[0134] (4) Enzymatic extraction method

[0135] The medicinal materials were weighed according to the formula ratio, coarsely crushed, and then 10 times the amount of water and 2.0% cellulase were added. The mixture was extracted for 24 hours at 50℃ and pH 5.0. After boiling, the mixture was filtered, the filtrate was concentrated and diluted to an appropriate volume, and the contents of alkaloids, polysaccharides and flavonoids were determined. The results are shown in Table 1.

[0136] (5) Enzymatic hydrolysis and decoction method

[0137] The medicinal materials were weighed according to the formulation ratio, coarsely pulverized, and then added with 10 times the amount of water and 2.0% cellulase. The mixture was extracted for 24 hours at 50℃ and pH 5.0. After boiling for 30 minutes, the mixture was filtered to obtain the enzymatic extract. The residue was added with 8 times the amount of water, heated and decocted for 30 minutes, filtered, and the filtrate was combined with the above enzymatic extract. The mixture was then concentrated and adjusted to an appropriate volume. The contents of alkaloids, polysaccharides, and flavonoids were determined. The results are shown in Table 1.

[0138]

[0139] The experimental results show that the content of various active ingredients in the enzymatic hydrolysis decoction method is significantly better than that in the traditional water extraction method. Therefore, the preparation process of this invention adopts the enzymatic hydrolysis decoction method.

[0140] 2. Optimization of process parameters for enzymatic hydrolysis and decoction method

[0141] (1) Investigation on the amount of water added for enzymatic hydrolysis

[0142] Weigh out the medicinal materials according to the formula ratio, a total of 3 portions, coarsely crush (pass through a 10-mesh sieve), and add 6 times, 8 times, and 10 times the amount of water and 2.0% cellulase respectively. Soak for 24 hours at 50℃ and pH 5.0, boil for 15 minutes, filter, concentrate the filtrate and make up to an appropriate volume, and determine the contents of alkaloids, polysaccharides and flavonoids. The results are shown in Table 2.

[0143]

[0144] The experimental results show that the amount of water added has little effect on the enzymatic extraction effect, and the amount of water added can be determined according to the specific circumstances during the enzymatic hydrolysis of medicinal materials.

[0145] (2) Investigation on the dosage of cellulase

[0146] Weigh out the medicinal materials according to the formula ratio, a total of 3 portions, coarsely crush (pass through a 10-mesh sieve), add 10 times the amount of water, and then add 1.0%, 2.0% and 3.0% cellulase respectively. Soak for 24 hours at 50℃ and pH 5.0, boil for 15 minutes and filter, concentrate the filtrate and make up to an appropriate volume, and determine the contents of alkaloids, polysaccharides and flavonoids. The results are shown in Table 3.

[0147]

[0148] The experimental results show that the effective components in the extracts with cellulase dosages of 2.0% and 3.0% are not significantly different, but are significantly higher than those with a cellulase dosage of 1.0%. Therefore, a cellulase dosage of 2.0% can be selected as the optimal process parameter.

[0149] (3) Investigation of extraction time

[0150] Weigh out the medicinal materials according to the formula ratio, a total of 3 portions, coarsely crush (pass through a 10-mesh sieve), add 10 times the amount of water, add 2.0% cellulase, and extract at 50℃ and pH 5.0 for 24 hours, 36 hours and 48 hours respectively. After boiling for 15 minutes, filter, concentrate the filtrate and make up to an appropriate volume, and determine the contents of alkaloids, polysaccharides and flavonoids. The results are shown in Table 4.

[0151]

[0152] The experimental results show that the effective components in the extracts after 36 hours and 48 hours of extraction are not significantly different, but both are higher than those after 24 hours of extraction. Therefore, 36 hours of extraction can be selected as the optimal process parameter.

[0153] (4) Investigation on the amount of water added during decoction

[0154] Three portions of medicinal materials were weighed according to the formulation ratio. After coarsely pulverizing (passing through a 10-mesh sieve), 10 times the amount of water was added, along with 2.0% cellulase. The mixture was extracted for 36 hours at 50℃ and pH 5.0, boiled for 15 minutes, and then filtered to obtain the enzymatic extract. The residue was then added to 4, 6, and 8 times the total amount of water of the medicinal materials, respectively, and decocted for 30 minutes. The decoctions were then filtered to obtain the aqueous extracts. The two extracts were combined, concentrated, and brought to a suitable volume. The contents of alkaloids, polysaccharides, and flavonoids were determined, and the results are shown in Table 5.

[0155]

[0156] The experimental results show that the amount of water added has little effect on the water decoction extraction effect. Therefore, the amount of water added can be determined according to the specific situation during the extraction of medicinal residue.

[0157] (5) Decoction time

[0158] Three portions of medicinal materials were weighed according to the formula proportions. After coarsely pulverizing (passing through a 10-mesh sieve), 10 times the amount of water was added, along with 2.0% cellulase. The mixture was extracted at 50℃ and pH 5.0 for 36 hours, boiled for 15 minutes, and then filtered to obtain the enzymatic extract. The residue was then added to 8 times the amount of water of the medicinal materials and decocted for 15, 30, and 45 minutes respectively, followed by filtration to obtain the aqueous decoction. The two extracts were combined, concentrated, and brought to a suitable volume. The contents of alkaloids, polysaccharides, and flavonoids were determined, and the results are shown in Table 6.

[0159]

[0160] The experimental results show that the decoction time has little effect on the extraction effect. In order to save energy and reduce processing costs, 15 minutes of decoction can be selected as the optimal process parameter.

[0161] (6) Validation of the optimal extraction process

[0162] Based on the aforementioned experimental results, the following parameters were selected as the optimal process: Weigh the medicinal materials according to the formulation ratio, coarsely crush (pass through a 10-mesh sieve), add 8 times the amount of water, add 2.0% cellulase, and extract at 50℃ and pH 5.0 for 36 hours. After boiling for 15 minutes, filter to obtain the enzymatic extract. Add 8 times the amount of water to the residue, heat and decoct for 15 minutes respectively, filter to obtain the aqueous decoction, combine the two extracts, concentrate and adjust the volume to an appropriate amount.

[0163] To verify the above optimal process parameters, a verification experiment was conducted, and the results are shown in Table 7.

[0164]

[0165] The verification results show that the extraction process has good repeatability, is reasonable and feasible, and can be used as the optimal extraction process for this prescription.

[0166] III. Clinical efficacy verification

[0167] As can be seen from the results of the aforementioned "Preparation Process Optimization Experiment", the content of effective components in the extract of the drug combination of the present invention is doubled compared with the original method of use (water decoction) after processing by the "enzymatic hydrolysis and water decoction" process. Theoretically, the dosage can be halved. In order to verify the advancement and rationality of the process, the team of the present invention took half of the original dosage of medicinal materials, extracted them by the "enzymatic hydrolysis and water decoction" process and made them into granules, and further carried out clinical efficacy verification experiments.

[0168] 1. Materials and Methods

[0169] (1) Clinical data

[0170] One hundred elderly patients with insomnia and nocturia admitted to the outpatient department of *** Traditional Chinese Medicine Hospital from February 2021 to January 2023 were selected as the study subjects. A random number table was generated using SAS statistical software, and the 100 patients were randomly divided into a treatment group and a control group at a 1:1 ratio, with 50 patients in each group. There were no statistically significant differences in age, disease duration, or other general characteristics between the two groups, making them comparable.

[0171] (2) Diagnostic criteria

[0172] The diagnosis of insomnia is based on the "Guidelines for the Diagnosis and Treatment of Insomnia in Chinese Adults (2017 Edition)". Insomnia due to heart-kidney disharmony mainly includes the following symptoms: Primary symptom: difficulty falling asleep, or even complete sleeplessness; Secondary symptoms: ① frequent urination at night; ② restlessness, dizziness, and tinnitus; ③ hot flashes and night sweats; ④ forgetfulness; ⑤ constipation. The syndrome is confirmed by the presence of two or more primary and secondary symptoms.

[0173] (3) Treatment methods

[0174] The control group took estazolam tablets orally before bedtime, 1 mg once daily. In addition to the control group's medication, the treatment group received granules of the product prepared according to the method of Example 11 of this invention, three times daily (each dose equivalent to half the original prescription dosage). Both groups received the medication for four weeks, and the treatment outcomes were observed.

[0175] (4) Observation indicators and efficacy assessment

[0176] The Insomnia Severity Index (ISI) was used, with higher scores indicating more severe insomnia. Both groups completed the ISI before and after treatment. The evaluation criteria for syndrome differentiation and efficacy were based on the "Standards for Diagnosis and Efficacy Assessment of Internal Medicine Diseases in Traditional Chinese Medicine." Clinical cure: main symptoms disappeared or largely disappeared; significant effect: main symptoms significantly improved; effective: main symptoms improved; ineffective: main symptoms did not improve. Total effective = clinical cure + significant effect + effective. Both groups of patients completed the ISI before and after treatment, conducting a self-assessment (patient). The total score was 28 points: 0-7 points: no significant insomnia; 8-14 points: sub-insomnia state; 15-21 points: clinical insomnia (mild); 22-28 points: severe insomnia.

[0177] 2. Results

[0178] (1) ISI score

[0179] After treatment, the improvement in ISI scores in the treatment group was significantly lower than that in the control group, and the difference was statistically significant (P < 0.05). See Table 8.

[0180]

[0181] (2) Improvement of clinical symptoms

[0182] After treatment, the treatment group showed greater improvement in symptoms such as insomnia, nocturia, irritability, dizziness, hot flashes, night sweats, and constipation than the control group, with statistically significant differences (P < 0.05). There were no statistically significant differences between the two groups in the improvement of tinnitus and forgetfulness (P > 0.05). See Table 9.

[0183]

[0184] (3) Comparison of clinical efficacy between the two groups of patients

[0185] The total effective rates in the treatment group and the control group were 88.0% and 66.0%, respectively. The total effective rate in the treatment group was significantly higher than that in the control group (P < 0.05). See Table 10.

[0186]

[0187] (4) Comparison of adverse reactions between the two groups of patients

[0188] During the study, two patients in the control group experienced fatigue and one patient experienced dry mouth, but the symptoms were mild. No adverse reactions occurred in the treatment group.

[0189] 3. Conclusion

[0190] As can be seen from the aforementioned clinical efficacy verification results, when the preparation made from medicinal materials using half the original clinical dosage according to the "enzymatic hydrolysis and decoction method" of this invention is used in clinical practice, the efficacy is significant and there are no obvious side effects. This indicates that the "enzymatic hydrolysis and decoction method" process is reasonable and achieves half the amount of medicinal materials used, effectively saving medicinal resources.

[0191] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

[0192] Analysis of typical cases:

[0193] 1. Patient XX, male, 65 years old, first visit on October 24, 2023. Chief complaint: Insomnia for 3 years, worsening for 1+ months. Three years ago, the patient developed symptoms of frequent awakenings at night and difficulty falling back asleep due to work fatigue and irregular sleep patterns. He would wake up around 2 AM and find it difficult to fall back asleep, experiencing fatigue upon waking. He had previously consulted a community clinic and was treated with oral estazolam tablets, but the medication was taken irregularly. One month ago, the patient reported that the above symptoms had worsened, accompanied by irritability upon waking, and thus sought medical attention. Current symptoms: shallow sleep, frequent awakenings, difficulty falling asleep, approximately 4 hours of sleep per night, occasionally sleepless nights, daytime fatigue, lethargy, poor concentration, lower back and knee weakness, accompanied by irritability, poor appetite, nocturia 3-4 times, normal bowel movements, alert and mentally sound, red tongue with yellow coating, and rapid pulse. The Insomnia Severity Index (ISI) score was 21.

[0194] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0195] Western medical diagnosis: Sleep disorder.

[0196] Treatment principle: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0197] Treatment: Prepare the prescription of Example 1 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0198] Follow-up visit: Sleep quality has significantly improved compared to before, with approximately 6 hours of sleep per night. There is no significant fatigue, lethargy, or lack of energy. There is also no difficulty concentrating, lower back and knee pain, occasional irritability, fair appetite, 2 nocturia, normal bowel movements, alertness, and fair mental state. The tongue is red with a thin white coating, and the pulse is rapid. The Insomnia Severity Index (ISI) score is 10.

[0199] 2. Patient XX, female, 62 years old, first visit on February 3, 2023. Chief complaint: Insomnia for 3+ months. Three months prior, the patient developed nighttime sleep disturbances with frequent awakenings and vivid dreams, often waking between 3-4 AM without any obvious cause. She had difficulty falling back asleep, resulting in less than 5 hours of sleep per night. Current symptoms: difficulty falling asleep, frequent awakenings and vivid dreams, accompanied by palpitations, fatigue, memory loss, hot flashes, night sweats, fair appetite, constipation, and frequent urination 3-4 times at night. She is alert and in good spirits, with a pale complexion, pale red tongue with a white coating, and a thready, rapid pulse. Her Insomnia Severity Index (ISI) score is 22.

[0200] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0201] Western medical diagnosis: Sleep disorder.

[0202] Treatment principle: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0203] Treatment: Prepare the prescription of Example 1 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0204] Follow-up visit: The patient falls asleep easily with few dreams, has no significant palpitations or fatigue, and has experienced significant improvement in memory loss, hot flashes, and night sweats. Appetite is fair, bowel movements are normal, and there are 1-2 frequent urinations at night. The patient is alert and in good spirits, with a normal complexion, a pale red tongue with a white coating, and a thready pulse. The Insomnia Severity Index (ISI) score is 12.

[0205] Patient XX, male, 70 years old, first visit on April 6, 2023. Chief complaint: Insomnia for 4+ years, worsening for 1+ months. The patient first experienced insomnia 4+ years ago due to family matters, and it has persisted ever since. He needs to take zopiclone daily to fall asleep, and after falling asleep, he wakes up easily and has many dreams. In the past month, his insomnia has worsened, seriously affecting his physical and mental health and daily life. Current symptoms: Insomnia, irritability, palpitations, and vivid dreams, accompanied by soreness and weakness in the lower back and knees, weakness in the limbs, occasional nocturnal emission, dark red tongue with thin white coating, thready and rapid pulse, normal bowel movements, and frequent urination at night (4-5 times). The Insomnia Severity Index (ISI) score is 23.

[0206] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0207] Western medical diagnosis: Sleep disorder.

[0208] Treatment principle: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0209] Treatment: Prepare the prescription of Example 1 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0210] Follow-up visit: Sleep is fair, mental state is good, no obvious palpitations, few dreams, slight soreness in the lower back and knees, no obvious nocturnal emission, red tongue with thin white coating, thready pulse, normal bowel movements, normal urination. Insomnia Severity Index (ISI) score is 9.

[0211] 4. Patient XX, male, 66 years old, first visit on May 20, 2023, with insomnia for 6+ months. Current symptoms: difficulty falling asleep, frequent awakenings, difficulty falling back asleep after waking, 3-4 hours of sleep per night, palpitations, vivid dreams, frequent colds, irritability, fatigue, night sweats. Pale red tongue with thin yellow coating, thready and rapid pulse, frequent urination at night, 3-4 times / night, normal bowel movements. History of hypertension, treated with medication, blood pressure is basically stable. Insomnia Severity Index (ISI) score: 19.

[0212] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0213] Western medical diagnosis: Sleep disorder.

[0214] Treatment principle: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0215] Treatment: Prepare the prescription of Example 2 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0216] Follow-up visit: Sleeps easily, 6-7 hours per night, few dreams, good mood, fatigue, occasional hot flashes and night sweats. Pale red tongue with thin yellow coating, thready pulse, normal urination and bowel movements. Insomnia Severity Index (ISI) score: 9.

[0217] Patient 5.XX, female, 60 years old, first visit on March 18, 2023. Chief complaint: Insomnia for 3+ years, worsening for 2 weeks. The patient developed insomnia 3+ years ago without obvious cause, characterized by vivid dreams and frequent awakenings, waking 4-5 times per night, mainly nightmares, often accompanied by feelings of fear. She took alprazolam tablets orally every night for symptomatic treatment, but the effect was significantly reduced recently. Two weeks ago, the insomnia worsened, with frequent vivid dreams and frequent awakenings, waking 7-8 times per night, and the frequency of nightmares increased, resulting in 3-5 hours of interrupted sleep each night. Current symptoms: Insomnia with vivid dreams, depressed mood, occasional irritability, usual forgetfulness, dizziness and tinnitus, lower back and knee weakness, aversion to cold, dry mouth and bitter taste, poor appetite, abdominal distension after meals, frequent urination (3-4 times at night), and dry, difficult bowel movements. Tongue: pale red with white coating; pulse: thready and rapid. The Insomnia Severity Index (ISI) score was 24.

[0218] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0219] Western medical diagnosis: Sleep disorder.

[0220] Treatment principles: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0221] Treatment: Prepare the prescription of Example 4 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0222] Follow-up visit: Sleep is fair, with few dreams, but the patient experiences depression, occasional dizziness, tinnitus, and lower back and knee weakness. Appetite is fair, but the patient urinates frequently, twice at night, and has dry, difficult bowel movements. The tongue is pale red with a white coating, and the pulse is thready and rapid. The Insomnia Severity Index (ISI) score is 13.

[0223] Patient 6.XX, female, 68 years old, first visit on November 5, 2023. Chief complaint: Insomnia for 1+ years. The patient usually stays up late and has significant family pressure. For the past year, she has experienced difficulty falling asleep, sometimes even unable to sleep at all. She has difficulty concentrating at work during the day and is pessimistic about life. Currently, she can temporarily fall asleep for 3-4 hours with diazepam tablets, but feels dizzy and weak after waking up. She has tried self-medicating with jujube seed calming capsules, basilicone capsules, and calming and brain-nourishing oral liquid, all with poor results. Current symptoms: difficulty falling asleep, occasional irritability, lethargy, lower back and knee weakness, loose stools, clear and copious urine, frequent urination at night (3-4 times), red tongue with thin white coating, and thready and rapid pulse. Insomnia Severity Index (ISI) score: 24.

[0224] Traditional Chinese Medicine diagnosis: Insomnia (disharmony between the heart and kidneys).

[0225] Western medical diagnosis: Sleep disorder.

[0226] Treatment principle: Tonify the kidneys and clear heat, harmonize the heart and kidneys.

[0227] Treatment: Prepare the prescription of Example 6 into granules according to the preparation method of Example 11, dissolve in water and take orally three times a day for 4 weeks.

[0228] Follow-up visit: Sleep is okay, slight soreness and weakness in the lower back and knees, normal bowel movements, regular urination, nocturia (1-2 times), red tongue with thin white coating, thready and rapid pulse. Insomnia Severity Index (ISI) score: 12.

Claims

1. A pharmaceutical composition for treating insomnia combined with nocturia in the elderly, characterized by comprising, The medicine composition is made from the following raw material components by weight: 450g of Radix Cinnamomi, 450g of Radix Cinnamomi, 300g of Fritillaria, 450g of Ganoderma, 240g of Piptanthus, 210g of Eel, 210g of Radix Rubi, 210g of Acorus calamus, and 90g of Fructus Jujubae; the preparation method of the medicine composition comprises the following steps: (1) weighing the medicinal materials: weighing the Radix Cinnamomi, Radix Cinnamomi, Fritillaria, Ganoderma, Piptanthus, Eel, Radix Rubi, Acorus calamus, and Fructus Jujubae according to the prescription proportion; (2) coarsely crushing the medicinal materials: mixing all the medicinal materials in step (1) and crushing them into the coarsest powder with a mesh size of 10; (3) enzymatic extraction: adding 8 times the total amount of medicinal materials of water, and then adding 1.5% of cellulase, and then soaking and extracting at 50°C and pH 5.0 for 36 hours, and then boiling for 30 minutes, and then filtering to obtain the enzymatic extraction liquid; (4) water decoction: adding 6 times the total amount of medicinal materials of water to the residue after filtering in step (3), and then heating and decocting for 30 minutes, and then filtering to obtain the water decoction liquid; (5) concentration: combining the water decoction liquid and the enzymatic extraction liquid, and then concentrating to a thick paste; (6) preparing the corresponding dosage form: adding 250g of microcrystalline cellulose, 5g of aspartame, and an appropriate amount of soluble starch to the thick paste, and then mixing uniformly, and then granulating with an 18-mesh sieve, and then drying at 70°C, and then integrating the granules, and then preparing 1000g of granules, and then obtaining the granules.

2. The use of the medicine composition in claim 1 in the preparation of a medicine preparation for treating insomnia combined with senile nocturia caused by heart-kidney disharmony.

3. Use according to claim 2, characterized in that, The medicine preparation comprises the medicine composition in claim 1 or the thick paste prepared by the preparation method, and a pharmaceutically acceptable adjuvant.

4. Use according to claim 3, characterized in that, The medicine preparation is a solid preparation or a liquid preparation.

5. Use according to claim 4, characterized in that, The solid preparation is granules, capsules, tablets, or pills; and the liquid preparation is an oral liquid.

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