Valerian and application of valerian preparation in preparation of medicine for treating chronic cholecystitis

Abstract

The invention provides valerian and application of a valerian preparation in preparation of a medicine for treating chronic cholecystitis. The valerian is an oral preparation prepared from a valerian medicinal material or a valerian extract as an active ingredient according to a conventional preparation method. The oral preparation is an electuary, a granule, a micro-capsule, a soft capsule, a tablet or an oral liquid. The valerian has the effects of soothing liver-qi stagnation, promoting blood circulation to remove blood stasis, promoting qi circulation to relieve pain and removing toxicity for detumescence, pharmacological experiments show that the valerian and the preparation thereof have the effects of improving immunity and resisting infection of pathogenic microorganisms and can accelerate excretion of gall bladder bile of mice, and the effects may be the pharmacological basis of the effects of soothing liver-qi stagnation, regulating qi and relieving pain; the effective rates of the traditional Chinese medicine for treating qi stagnation and blood stasis type chronic cholecystitis and liver and gall qi stagnation type chronic cholecystitis are 96.0% and 92.8% respectively, the curative effect is remarkable, and the cure rate is high. The traditional Chinese medicine composition is good in clinical curative effect, high in safety and few in adverse reaction, and a new method is provided for clinical treatment of chronic cholecystitis.

Description

Technical Field

[0001] This invention belongs to the field of natural medicine, specifically relating to the application of valerian and its preparations in the preparation of drugs for treating chronic cholecystitis. Background Technology

[0002] Cholecystitis is an inflammatory condition of the gallbladder caused by bacterial infection or chemical irritation (alteration of bile composition), and is a common disease of the gallbladder. Depending on the stage and severity of the inflammation, cholecystitis can be divided into acute cholecystitis and chronic cholecystitis. Cholecystitis commonly occurs between the ages of 20 and 50. The incidence of gallstones is higher in women than in men, and the incidence increases with age. If left untreated, it can lead to acute suppurative cholangitis, biliary pancreatitis, etc. Chronic cholecystitis is a common biliary tract disease in clinical practice, often a sequela of acute cholecystitis. In elderly patients, it is often a complication of cholelithiasis. Its main clinical manifestations are right upper quadrant pain and indigestion, which are often misdiagnosed as stomach problems. Symptoms worsen or trigger acute attacks during emotional distress or dietary indiscretions.

[0003] Cholecystitis is an inflammatory dysfunction of the gallbladder and bile ducts caused by factors such as cholestasis (gallstones, gallbladder emptying disorders after vagotomy), infectious factors (E. coli, Klebsiella, anaerobic bacteria infections, etc.), metabolic factors (pancreatic juice reflux, altered bile acid ratios), and vascular factors (gallbladder wall vascular lesions, impaired gallbladder concentration). Cholecystitis is a common acute abdominal condition in surgery, second only to appendicitis in incidence among inflammatory acute abdomens. Currently, Western medicine lacks a superior treatment for cholecystitis, generally using antibiotics and anti-inflammatory analgesics for symptomatic relief, but the efficacy is unsatisfactory, the recurrence rate is high, and the cost is high. Although laparoscopic cholecystectomy has become the main treatment for cholecystitis, postoperative recurrence or postoperative indigestion may occur, leading many patients to fear surgery and choose conservative treatment. Compared with Western medicine, Traditional Chinese Medicine (TCM), guided by its unique syndrome differentiation and treatment principles and the integration of disease and syndrome, takes a holistic approach, addressing both the root cause and symptoms, effectively alleviating patient suffering and improving their quality of life.

[0004] Based on clinical manifestations, cholecystitis falls under the categories of gallbladder distension, hypochondriac pain, and abdominal pain in Traditional Chinese Medicine (TCM). Records of "hypochondriac pain" and "gallbladder distension" can be found as early as the *Huangdi Neijing* (Yellow Emperor's Inner Classic). The *Suwen* (Plain Questions) section on "Miao Ci Lun" (Discourse on Acupuncture and Moxibustion) states: "Evil invading the Shaoyang meridian of the foot causes hypochondriac pain and difficulty breathing." This indicates that external pathogens invading the Shaoyang meridian lead to impaired circulation, resulting in pain due to obstruction. Yan Yonghe, in *Jisheng Fang* (Formulas for Saving Lives) on "Treatment of Hypochondriac Pain," points out that "hypochondriac pain...is mostly caused by extreme fatigue, anger, sorrow, worry, and anxiety, which damages the liver. Once the liver is damaged, accumulated qi attacks and flows; if it attacks the left, there is pain in the left hypochondriac region; if it attacks the right, there is pain in the right hypochondriac region; if it shifts between the two hypochondriac regions, both hypochondriac regions are painful." This indicates that the disease is caused by stagnation of liver and gallbladder qi. TCM treatment for this disease primarily focuses on clearing and draining the liver and gallbladder, soothing the liver and regulating qi, and regulating the flow of qi.

[0005] Valerian is the dried rhizome and root of *Valeriana pseudofcinalis* CYCheng et HHChen, a plant in the Valerianaceae family. It is pungent, sweet, and warm in nature. It enters the heart and liver meridians. Its functions and indications include calming the mind, regulating qi, and relieving pain. It is used for restlessness, palpitations, insomnia, depression, epilepsy, abdominal distension and pain, lumbago, and traumatic injuries. Valerian is sweet and primarily enters the heart and liver meridians, possessing calming, qi-regulating, and depression-relieving effects. It is used to treat restlessness, palpitations, depression, and epilepsy. Modern pharmacological experiments have shown that it has sedative, antidepressant, anti-anxiety, anti-epileptic, anticonvulsant, memory-improving, and anti-cerebral ischemia-related central nervous system effects. It also has antiarrhythmic, lipid-lowering, and kidney-protective pharmacological effects. Valerian has the effects of soothing the liver, regulating qi, relieving depression, promoting blood circulation, removing blood stasis, and relieving pain, and has potential therapeutic effects on chronic cholecystitis. However, there are no clinical reports in the existing literature regarding the use of valerian for the prevention and improvement of chronic cholecystitis. Summary of the Invention

[0006] In view of the above-mentioned prior art, the present invention provides an application of valerian and its preparations in the preparation of drugs for treating chronic cholecystitis.

[0007] This invention is achieved through the following technical solution: This invention provides the use of valerian and its preparations in the preparation of a medicament for treating chronic cholecystitis.

[0008] As a further explanation of the present invention, the valerian and its preparations are oral preparations made by using valerian herbal material or valerian extract as active ingredients and following conventional preparation methods; the oral preparations are powders, granules, microcapsules, soft capsules, tablets or oral liquids.

[0009] Preferably, the formulation uses valerian extract as the active component, and adds conventional pharmaceutical excipients and / or carriers required for the preparation of different dosage forms, in the following weight ratio: 2-10% valerian extract, 98%-90% pharmaceutical excipients and / or carriers, to prepare an oral formulation.

[0010] Preferably, the method for preparing the valerian extract involves extracting the effective components of valerian using supercritical carbon dioxide extraction at an extraction temperature below 40°C. Specifically, the method includes the following steps: taking coarse valerian powder, employing supercritical carbon dioxide extraction technology at an extraction temperature of 30–40°C, an extraction pressure of 20–30 MPa, and using an entrainer at a volume of 2–4 times the weight of the herb. The entrainer is measured in ml, and the herb weight is measured in g. The entrainer is selected from methanol, anhydrous ethanol, or 95% ethanol. The desorption temperature is 30–40°C, the desorption pressure is 3–6 MPa, the CO2 flow rate is 10–20 L / h, and the extraction time is 1–2 h.

[0011] As a further explanation of the present invention, the preparation is made by mixing and grinding valerian volatile oil inclusions and extract powder. Preferably, the valerian preparation is made by mixing and grinding valerian volatile oil inclusions and extract powder. Furthermore, the preparation method of the valerian preparation includes the following steps: 1) Fresh valerian rhizomes and roots are used. After washing away the dirt and draining, they are chopped into 1-5cm long pieces and then distilled using a water-double-barrel pressurized direct steam distillation method. The initial steam pressure is 0.08-0.12mPa / cm². 2 During the distillation process, the steam pressure was 0.02-0.06 mPa / cm. 2 The steam pressure in the later stage of distillation is 0.08-0.10 mPa / cm. 2 The process lasts for 1.5-2.5 hours, during which volatile oil and medicinal residue are separated. 2) Pre-drying of the dregs: Sun-dry, oven-dry, or vacuum-dry, place in a percolation tank and tamp down, soak in 70-95% v / v ethanol (1.5 times the amount of fresh medicinal material) for 8-12 hours and then begin percolation. After filtering the percolate and recovering the ethanol, concentrate and dry to obtain valerian dry extract, grind and sieve to obtain valerian extract powder. 3) Take 2-5 times the weight of β-cyclodextrin of volatile oil, add 1-2 times the amount of distilled water and grind evenly. Then add valerian volatile oil and grind thoroughly for 20-40 minutes to form a volatile oil mixture. Filter to remove water, wash away the un-encapsulated volatile oil with petroleum ether at a boiling range of 30-60℃, and dry at room temperature, air dry, or vacuum dry. Grind and sieve to obtain valerian volatile oil β-cyclodextrin inclusion powder. 4) The β-cyclodextrin inclusion complex powder of valerian volatile oil is mixed with valerian extract powder, and starch is added to the fill weight. After mixing evenly, the mixture is passed through a 38-45 mesh sieve and then encapsulated to form capsules. The valerian preparation is made from the following raw materials in parts by weight: raw material weight Valerian volatile oil 65-68mg β-Cyclodextrin 195-264mg Valerian extract powder 24-30mg Medicinal starch 18-24mg 70% ethanol 28-32mg magnesium stearate 0.6-0.7mg talcum powder 0.3-0.4mg .

[0012] More preferably, the valerian preparation is made from the following raw materials in parts by weight: raw material weight Valerian volatile oil 66-68mg β-Cyclodextrin 198-206mg Valerian extract powder 26-28mg Medicinal starch 20-22mg 70% ethanol 29-30mg magnesium stearate 0.6-0.65mg talcum powder 0.3-0.35mg The valerian volatile oil is a pale yellow clear liquid with a fragrant aroma and a slightly pungent taste. It has a relative density of 0.94-0.96, a refractive index of 1.48-1.49, a heavy metal content of no more than 10 parts per million, and a bornyl acetate content of ≥ 27%. The valerian extract powder is a brownish-brown powder with a moisture content of <5%, a valerian terpene lactone A content of ≥1.3%, and a total terpene lactone content of ≥8.0%. Each capsule contains 0.29g and contains ≥40mg of valerian volatile oil, 25±3mg of valerian extract, >12mg of bornyl acetate, >0.38mg of valerian lactone A, and >5.5mg of total terpene lactones.

[0013] Furthermore, the valerian preparation is Rick® Valerian Extract Capsules produced by Wuhan United Pharmaceutical Co., Ltd.

[0014] The non-pharmaceutical active ingredients such as carriers, excipients, and diluents that may be included in this invention are well known in the art, and those skilled in the art can determine that they meet clinical standards.

[0015] According to the literature: Expert Consensus on the Diagnosis and Treatment of (Acute and Chronic) Cholecystitis and Cholelithiasis in Traditional Chinese Medicine (2023), acute cholecystitis is mainly characterized by "heat and toxicity," and the main treatments are clearing heat and dampness, promoting qi circulation and gallbladder function, and purging fire from the bowels. In the acute phase, it is differentiated into two syndromes: gallbladder and visceral heat stagnation syndrome and heat-toxin excess syndrome. In the remission phase, it is differentiated into two syndromes: liver yin deficiency syndrome and blood stasis syndrome. Chronic cholecystitis is mainly characterized by "dampness, stagnation, and blood stasis," and may also present with "spleen deficiency and yin deficiency" syndromes. It can be divided into 7 syndrome types: liver and gallbladder qi stagnation syndrome, liver and gallbladder damp-heat syndrome, gallbladder heat and spleen cold syndrome, qi stagnation and blood stasis syndrome, liver stagnation and spleen deficiency syndrome, liver yin deficiency syndrome, and spleen and stomach qi deficiency syndrome.

[0016] Many patients with chronic cholecystitis continue to use the same treatments used during the acute phase, such as clearing liver fire and purging heat and dampness. As a result, their condition worsens with each treatment. This is because using only bitter and cold herbs to clear heat and purge fire can only clear the heat that is scattered and spread throughout the three jiaos. It does not have the effect of relieving stagnation and opening up the stagnation. The internal heat has no way to be released, so the heat becomes even more intense due to the stagnation.

[0017] Chronic cholecystitis falls under the categories of "hypochondriac pain" and "stomach pain" in Traditional Chinese Medicine (TCM). TCM believes that emotional distress, exposure to cold or heat, improper diet, excessive consumption of oily foods, or intestinal parasites can all lead to stagnation of liver and gallbladder qi, impaired spleen function, and accumulation of damp-heat, affecting the liver's function of dispersing and draining qi and the gallbladder's function of descending qi, thus causing this disease. Bile originates from the liver, and its secretion and excretion are achieved through liver function. Bile is formed by "the excess qi of the liver overflowing into the gallbladder and accumulating." Liver stagnation leads to disharmony of liver qi, resulting in qi stagnation. Qi stagnation causes abnormal liver function of dispersing and draining qi, which in turn leads to abnormal bile secretion and excretion. Prolonged stagnation of gallbladder qi leads to poor blood circulation and blood stasis, phlegm and heat accumulation, obstruction of the middle jiao (middle burner), and impaired function of the pivot, resulting in "blood stasis in the gallbladder vessels" and causing cholecystitis.

[0018] Among the seven syndrome types of chronic cholecystitis, hypochondriac pain is one of the main and persistent symptoms, often due to qi stagnation in the chronic phase. The applicant believes that the pathogenesis of chronic cholecystitis is mainly related to liver and gallbladder dysfunction, qi stagnation, and spleen and stomach imbalance, with liver qi stagnation being the primary cause. For patients with chronic cholecystitis, long-term illness and the pressures of life and society often lead to drastic emotional fluctuations and a tendency towards anxiety, which can trigger or relapse of the disease. The liver governs the free flow of qi; emotional distress can lead to liver qi stagnation, which in turn affects bile secretion and excretion, causing bile stasis in the gallbladder and resulting in cholecystitis. Liver qi stagnation: Emotional distress and liver qi stagnation lead to impaired qi flow in the gallbladder, obstructing bile excretion and causing distending pain in the right hypochondrium, with the pain often increasing or decreasing with emotional changes. Qi stagnation and blood stasis: Prolonged liver qi stagnation leads to poor blood circulation, internal blood stasis, and obstruction of the liver and gallbladder meridians, resulting in stabbing pain in the right hypochondrium, with a fixed location of pain and possibly a palpable mass under the ribs.

[0019] Chronic cholecystitis is often caused by emotional distress and stagnation of liver and gallbladder qi. Therefore, psychological treatment should be emphasized simultaneously during drug therapy. Emotional depression leads to liver qi stagnation, impaired liver function, disharmony between the liver and stomach, and obstructed blood and qi circulation. Prolonged stagnation can generate heat, hence the saying "excess qi becomes fire." Following the principles of traditional Chinese medicine, the treatment should focus on "relieving stagnant fire," meaning soothing the liver, relieving stagnation, and regulating qi to allow the stagnant fire in the liver and gallbladder to dissipate. The heart and gallbladder are interconnected: they are linked in terms of meridians and mental state. Emotional problems (such as anxiety and depression) can affect gallbladder function through this physiological connection, leading to or exacerbating cholecystitis. Based on the understanding of the pathogenesis and syndrome differentiation of this disease, the treatment of chronic cholecystitis should focus on soothing the liver, relieving stagnation, regulating qi, and relieving pain. Valerian has calming, liver-soothing, blood-activating, qi-regulating, pain-relieving, detoxifying, and swelling-reducing effects, making it a suitable treatment for chronic cholecystitis caused by liver and gallbladder qi stagnation and blood stasis.

[0020] The beneficial effects of this invention are: In this invention, valerian possesses the effects of soothing the liver and relieving depression, promoting blood circulation and removing blood stasis, regulating qi and relieving pain, and detoxifying and reducing swelling. Pharmacological experiments show that the valerian and its preparations in this invention can enhance immunity and resist infection by pathogenic microorganisms, and can accelerate the excretion of bile from the gallbladder of mice. This effect may be the pharmacological basis for its effects of soothing the liver and relieving depression, regulating qi and relieving pain. This application shows an effective rate of 96.0% and 92.8% in treating patients with chronic cholecystitis of the qi stagnation and blood stasis type and the liver and gallbladder qi stagnation type, respectively, demonstrating significant efficacy and a high cure rate. It has good clinical efficacy, high safety, and few adverse reactions, providing a new method for the clinical treatment of chronic cholecystitis. Detailed Embodiments The present invention will be further illustrated with specific examples. These examples are for illustrative purposes only and do not limit the scope of the invention. Unless otherwise specified, experimental conditions not explicitly stated in the examples are generally performed under conventional conditions or as recommended by the reagent company. The reagents and consumables used in the following examples are commercially available unless otherwise specified. The following examples further illustrate the invention but do not constitute a limitation thereof. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0021] Example 1. Preparation of a valerian preparation The valerian preparation is made from the following raw materials in parts by weight: raw material weight Valerian volatile oil 66-68mg β-Cyclodextrin 198-206mg Valerian extract powder 26-28mg Medicinal starch 20-22mg 70% ethanol 29-30mg magnesium stearate 0.6-0.65mg talcum powder 0.3-0.35mg The method for preparing the valerian preparation comprises the following steps: 1) Fresh valerian rhizomes and roots are used. After washing away the dirt and draining, they are chopped into 1-5cm long pieces and then distilled using a water-double-barrel pressurized direct steam distillation method. The initial steam pressure is 0.08-0.12mPa / cm². 2 During the distillation process, the steam pressure was 0.02-0.06 mPa / cm. 2 The steam pressure in the later stage of distillation is 0.08-0.10 mPa / cm. 2 The process lasts for 1.5-2.5 hours, during which volatile oil and medicinal residue are separated. 2) Pre-drying of the dregs: Sun-dry, oven-dry, or vacuum-dry, place in a percolation tank and tamp down, soak in 70-95% v / v ethanol (1.5 times the amount of fresh medicinal material) for 8-12 hours and then begin percolation. After filtering the percolate and recovering the ethanol, concentrate and dry to obtain valerian dry extract, grind and sieve to obtain valerian extract powder. 3) Take 2-5 times the weight of β-cyclodextrin of volatile oil, add 1-2 times the amount of distilled water and grind evenly. Then add valerian volatile oil and grind thoroughly for 20-40 minutes to form a volatile oil mixture. Filter to remove water, wash away the un-encapsulated volatile oil with petroleum ether at a boiling range of 30-60℃, and dry at room temperature, air dry, or vacuum dry. Grind and sieve to obtain valerian volatile oil β-cyclodextrin inclusion powder. 4) The β-cyclodextrin inclusion complex powder of valerian volatile oil is mixed with valerian extract powder and starch is added to the fill weight. After mixing evenly, the mixture is passed through a 38-45 mesh sieve and then filled into capsules to make capsules. The valerian volatile oil is a pale yellow clear liquid with a fragrant aroma and a slightly pungent taste. It has a relative density of 0.94-0.96, a refractive index of 1.48-1.49, a heavy metal content of no more than 10 parts per million, and a bornyl acetate content of ≥ 27%. The valerian extract powder is a brownish-brown powder with a moisture content of <5%, a valerian terpene lactone A content of ≥1.3%, and a total terpene lactone content of ≥8.0%. Each capsule contains 0.29g and contains ≥40mg of valerian volatile oil, 25±3mg of valerian extract, >12mg of bornyl acetate, >0.38mg of valerian lactone A, and >5.5mg of total terpene lactones.

[0022] Existing medicinal valerian preparations mainly include valerian powder, valerian extract, valerian tincture, and compound preparations. All are made from dried valerian as raw material, directly powdered or powdered and then extracted with low-to-medium concentration ethanol (60% or less). Preparations produced using existing techniques have extremely low valerian volatile oil content and low terpene lactone content. According to literature reports, the volatile oil content of valerian can decrease by 50% after six months of storage. Our observations show that the volatile oil content of fresh valerian from a certain region was 1.8%, but after two years of storage in a cool, shady indoor environment at high altitudes, the volatile oil content plummeted to 0.5%. Powdering the herb further significantly reduces the oil content. Secondly, valerian volatile oil is insoluble in low-to-medium concentration ethanol, and valerian terpene lactones are also poorly soluble in low-to-medium concentration ethanol. Therefore, valerian preparations made from dried valerian using low-to-medium concentration ethanol (60% or less) have extremely low valerian volatile oil and very low terpene lactone content. This invention utilizes the roots and rhizomes of fresh valerian. After rinsing to remove dirt and sand, draining, and slightly chopping (into 1-5cm pieces), the volatile oil is prepared using a water-double-barrel pressurized steam direct distillation method. During distillation, water is discarded from the distillation tank approximately every 1 / 2 hour, saving time and labor while achieving a high oil yield. The volatile oil extracted from fresh valerian is then encapsulated with β-cyclodextrin. This encapsulation process ensures stability, high encapsulation rate, significantly improving the stability of the formulation, accelerating absorption, and enhancing patient tolerance. Experiments show that the valerian volatile oil β-cyclodextrin-encapsulated compound, when placed in an open environment at 40℃ and 70% relative humidity for 90 days, exhibits a volatile oil loss rate of <5%. This minimizes the loss of volatile oil components, ensuring the stability and efficacy of the formulation.

[0023] Example 2. Preparation of a valerian preparation Preparation method of valerian extract: The effective components of valerian are extracted by supercritical carbon dioxide extraction at an extraction temperature below 40℃. The specific steps include: taking crude valerian powder, using supercritical carbon dioxide extraction technology, extraction temperature 30-40℃, extraction pressure 20-30MPa, the amount of entrainer is 2-4 times the weight of the herb, where the unit of entrainer amount is ml, the unit of herb weight is g, the entrainer is selected from methanol, anhydrous ethanol or 95% ethanol, desorption temperature 30-40℃, desorption pressure 3-6MPa, CO2 flow rate 10-20L / h, and extraction time 1-2h.

[0024] The valerian preparation is an oral formulation prepared using valerian herbal material or valerian extract as the active ingredient, according to conventional formulation methods; the oral formulation is a powder, granule, microcapsule, soft capsule, tablet or oral liquid.

[0025] Example 3. Preparation of a Valerian Preparation The valerian extract prepared by supercritical extraction in Example 2 was used as the active component. Conventional pharmaceutical excipients and / or carriers required for the preparation of different dosage forms were added to prepare a formulation for the treatment of chronic cholecystitis according to the following weight ratio: 2-10% valerian extract and 98%-90% pharmaceutical excipients and / or carriers.

[0026] Example 4. Preparation of a Valerian Preparation The valerian volatile oil β-cyclodextrin inclusion complex powder prepared in Example 1 was mixed with valerian extract powder as the active component. Conventional pharmaceutical excipients and / or carriers required for the preparation of different dosage forms were added to prepare a formulation for the treatment of chronic cholecystitis according to the following weight ratio: 2-10% valerian extract, 98%-90% pharmaceutical excipients and / or carriers.

[0027] Example 5. Study on the efficacy of the valerian extract of the present invention in animals. 1. Materials 1.1 Animals: British Shorthaired Class 1 guinea pigs, weighing 280–320g. Kunming Class 1 mice, half male and half female, weighing 22–25g, provided by the Experimental Animal Center of Hubei University of Traditional Chinese Medicine.

[0028] 1.2 Drugs Commercially available valerian extract capsules: manufactured by Wuhan United Pharmaceutical Co., Ltd.

[0029] 2. Methods 2.1 Replication of the cholecystitis model Fifty guinea pigs weighing 300–320g, half male and half female, were randomly divided into 5 groups. They were fed normally for 7 days. Starting on day 8, they were injected subcutaneously into the groin with lincomycin hydrochloride at a dose of 50 mg / (kg·d) for 7 consecutive days. During the modeling period, their food and water intake were unrestricted. The control group was fed normal feed and simultaneously injected subcutaneously with physiological saline at 0.2 mL / pig for 7 consecutive days.

[0030] Administration: After model establishment, guinea pigs were administered the drug via gavage. The small, medium, and large doses of valerian extract capsules were 0.5, 1.5, and 3.0 g / (kg·d), respectively, for 10 consecutive days. The normal group and the model group were given an equal volume of physiological saline via gavage (1 mL / guinea pig). On the second day after the last administration, the guinea pigs were fasted.

[0031] Blood was collected from the retroorbital venous plexus of guinea pigs for white blood cell count. The results are shown in Table 1.

[0032] Table 1. Effects of autocyte count in the blood of guinea pigs with cholecystitis model. Group <![CDATA[WBC(×10 3 / μL)]]> normal control group 7.12±1.88 Model control group 4.65±2.15 High-dose group of valerian extract 8.53±2.86* Valerian extract medium dose group 8.49±1.62* Low-dose group of valerian extract 7.62±2.37 Note: Compared with the control group, P < 0.05 (the same applies below). Leukocytes exhibit strong phagocytic function during the acute phase of infection. Severe trauma, infection, and other factors trigger a stress response in the body, affecting the neuroendocrine-immune network and leading to a decrease in leukocyte count. Bacterial toxins can also destroy leukocytes, reducing their count. Experiments have shown that high and medium doses of valerian extract can significantly counteract the decrease in leukocyte count in guinea pigs during the early stage of gallbladder infection, thus benefiting the body's fight against pathogenic microorganisms.

[0033] The animal was euthanized, and its bile was extracted. The bile was then diluted sequentially to 10... -3 10 -4 10 -5 10 -6 Take 0.1 mL of each dilution and drop it onto a nutrient agar plate. Make 3 plates for each dilution and incubate for 24 h. Count the aerobic bacteria on plates with 30-300 colonies. The results are shown in Table 2.

[0034] Table 2. Effects on bile aerobic bacteria (CFU) in a cholecystitis model guinea pig Group <![CDATA[CFU(×10 6 / mL)]]> normal control group 0.0009±0.0008 Model control group 34.65±30.18 High-dose group of valerian extract 10.53±5.86* Valerian extract medium dose group 8.49±6.62* Low-dose group of valerian extract 27.62±12.37 The results of this preparation on bile bacteria in a cholecystitis model guinea pig showed that the medium-dose group of valerian extract had the best inhibitory effect on aerobic bacteria in bile.

[0035] 2.3 Effects on bile excretion in mouse gallbladder Sixty mice were randomly divided into four groups and administered the drug twice daily for three days. Two hours after the last administration, the animals were sacrificed, their gallbladders were removed, and they were weighed. The results are shown in Table 3.

[0036] Table 3 Effects on bile excretion in mouse gallbladder Group Gallbladder weight (mg) saline group 14.55±5.68 Low-dose group of valerian extract 9.53±6.06* Valerian extract medium dose group 10.89±5.62 High-dose group of valerian extract 10.32±5.37 Liver qi stagnation encompasses a pathological process involving impaired liver and gallbladder excretion and disordered smooth muscle contraction in the bile ducts and intestines. This preparation can accelerate the excretion of bile from the gallbladder in mice, which may be the pharmacological basis for its effects of soothing the liver, relieving stagnation, regulating qi, and alleviating pain. In addition, the bile excretion effect also benefits the excretion of bile bacteria and toxins, reducing the incidence of bacteremia and toxemia.

[0037] Example 6. Study on the therapeutic effect of the present invention on chronic cholecystitis 1. Experimental Objective This study investigated the therapeutic effects of valerian extract capsules on chronic cholecystitis of the qi stagnation and blood stasis type and the liver and gallbladder qi stagnation type.

[0038] 2 Experimental Methods 2.1 General Information From December 2023 to May 2025, Hubei Provincial Hospital of Traditional Chinese Medicine admitted 53 patients with chronic cholecystitis, all of whom were diagnosed with chronic cholecystitis and classified according to TCM syndrome differentiation as either Qi stagnation and blood stasis type or liver and gallbladder Qi stagnation type. All patients met the Western medicine diagnostic criteria for chronic cholecystitis and the TCM diagnostic criteria for Qi stagnation and blood stasis syndrome and liver and gallbladder Qi stagnation type. The patients were divided into two groups based on their Qi stagnation and blood stasis type and liver and gallbladder Qi stagnation type: Control Group 1 (25 cases of liver and gallbladder Qi stagnation type) and Control Group 2 (28 cases of Qi stagnation and blood stasis type). Their ages ranged from 29 to 66 years, with a mean age of 43.5 years. There were no significant differences between the two groups in terms of age, gender, disease duration, and pain intensity.

[0039] 2.2 Diagnostic Criteria Based on the People's Republic of China Traditional Chinese Medicine Industry Standard "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" and the Expert Consensus Opinion on the Diagnosis and Treatment of (Acute and Chronic) Cholecystitis and Cholelithiasis in Traditional Chinese Medicine (2023), the patient was diagnosed with chronic cholecystitis.

[0040] Liver and gallbladder qi stagnation type: Main symptoms: ① Distending pain in the right hypochondrium; ② Irritability and anger.

[0041] Secondary symptoms: ① aversion to greasy food; ② occasional nausea; ③ vomiting after meals; ④ fullness and discomfort in the epigastrium and abdomen; ⑤ belching.

[0042] Tongue and pulse: ① The tongue is pale red with a thin white or greasy coating; ② The pulse is wiry.

[0043] Qi stagnation and blood stasis type: Main symptoms: ① distending or stabbing pain in the right hypochondrium; ② fullness and tightness in the chest; ③ frequent sighing.

[0044] Secondary symptoms: ① Bitter taste in the mouth upon waking; ② Dry throat; ③ Pain in the right hypochondrium that worsens at night; ④ Incomplete bowel movements or constipation.

[0045] Tongue and pulse: ① Dark purple tongue with thick, greasy coating; ② Wiry or wiry and hesitant pulse.

[0046] Syndrome diagnosis: A diagnosis can be made if the patient presents with the primary symptom ① plus another primary symptom and two secondary symptoms, and by referring to the tongue and pulse.

[0047] 2.3 Treatment methods Control group 1 (liver and gallbladder qi stagnation type) and control group 2 (qi stagnation and blood stasis type): Valerian extract capsules were administered orally, 2 capsules each time, 3 times a day. Both groups underwent a 4-week course of treatment, with one course constituting the clinical observation period. During treatment, all patients in both groups discontinued other Chinese and Western medications for chronic cholecystitis, avoided spicy, cold, high-fat, and difficult-to-digest foods, abstained from smoking and alcohol, and maintained emotional well-being.

[0048] 2.4 Criteria for Evaluating Therapeutic Effect Clinical symptoms were observed and recorded weekly before and after medication, with detailed records of changes in syndrome scores. Changes in abdominal signs and objective Western medical examinations performed before and after the course of treatment were also noted. The efficacy evaluation criteria were formulated in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines".

[0049] Clinical efficacy evaluation criteria: Cure: Clinical symptoms and signs completely disappear, and the score decreases by ≥95%; Significant effect: Clinical symptoms and signs are significantly improved, and the score is reduced by ≥70%; Effective: Clinical symptoms and signs improved, and the score decreased by ≥30%; Ineffective: Clinical symptoms and signs show no significant relief, and the score decreases by <30%.

[0050] The overall effective rate of clinical treatment = (cured + significantly effective + effective) / total number of cases × 100%.

[0051] Symptom scoring criteria: The main symptoms are scored as follows: none, mild, moderate, and severe, respectively, with scores of 0, 2, 4, and 6. Details are as follows: Right upper quadrant pain or discomfort 0 points: None 2 points: Mild pain or discomfort that does not affect work or rest.

[0052] 4 points: Moderate pain, with paroxysmal exacerbations, affecting work and rest.

[0053] 6 points: Severe pain, colic, requires antispasmodic and analgesic drugs.

[0054] The heating is disgusting 0 points: None 2 points: Occasionally there is heating, and I still feel nauseous after a fatty meal, but the degree is mild.

[0055] 4 points: Heating, occasional nausea, but no major impact on eating.

[0056] 6 points: Frequent use of heating causes nausea to occur frequently, resulting in severe pain and affecting eating.

[0057] Abdominal bloating worsens after eating greasy food 0 points: None 2 points: Abdominal distension and mild aversion to oily food, but still able to eat fatty meals.

[0058] 4 points: Abdominal distension, aversion to oily foods, and nausea after fatty meals.

[0059] 6 points: Persistent abdominal distension or tenderness upon palpation, extreme aversion to oily foods, nausea and vomiting after fatty meals.

[0060] tenderness or percussion pain in the gallbladder area 0 points 2 points: Mild tenderness or percussion pain in the gallbladder area.

[0061] 4 points: Moderate tenderness or percussion pain in the gallbladder area.

[0062] 6 points: Severe tenderness or percussion pain in the gallbladder area.

[0063] Ultrasound efficacy evaluation criteria Recovery: The thickness, roughness, and sound transmission of the gallbladder or bile duct wall return to normal.

[0064] Significant effect: Improvement in 2 or more of the above items.

[0065] Effective: Improvement in one or more of the above items.

[0066] Ineffective: None of the above three items showed improvement.

[0067] 2.5 Statistical Analysis Data were statistically processed using SPSS 3.0 software. Data for each experimental group were expressed as mean ± standard deviation, and significance was tested using the T-test.

[0068] 3. Results and Conclusions Table 4 Comparison of treatment effects and pain levels before and after treatment between the two groups of patients. Group Number of examples get well Effective efficient Overall effectiveness / % Control group 1 (liver and gallbladder qi stagnation type) 25 9（36.0） 11（44.0） 4（16.0） 96.0 Control group 2 (Qi stagnation and blood stasis type) 28 10（35.7） 12（42.9） 4（14.3） 92.8 The clinical efficacy of the two groups of patients was compared. The results showed that the effective rate of this application in treating patients with chronic cholecystitis of the qi stagnation and blood stasis type and the liver and gallbladder qi stagnation type was 96.0% and 92.8%, respectively. Valerian extract capsules have significant efficacy in treating chronic cholecystitis of the qi stagnation and blood stasis type and the liver and gallbladder qi stagnation type, with a high cure rate and positive clinical significance.

[0069] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of them. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention. Although the specific embodiments of the present invention have been described above in conjunction with the solutions, this is not a limitation on the protection scope of the present invention. Those skilled in the art should understand that various modifications or variations that can be made by those skilled in the art without creative effort based on the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. The use of valeriana officinalis and its preparations in the preparation of a drug for treating chronic cholecystitis.

2. Use according to claim 1, characterized in that, The valeriana officinalis is prepared into oral preparations by using valeriana officinalis medicinal materials or valeriana officinalis extract as active ingredients and following conventional preparation methods; the oral preparations are bolus, granules, microcapsules, soft capsules, tablets or oral liquids.

3. Use according to claim 2, characterized in that, The preparation uses valeriana officinalis extract as active components, adds conventional pharmaceutical adjuvants or / and carriers required for preparing different dosage forms, and follows the weight ratio of 2-10% valeriana officinalis extract, 98%-90% pharmaceutical adjuvants or / and carriers to prepare oral preparations.

4. Use according to claim 3, characterized in that, The preparation method of the valeriana officinalis extract is to extract effective components of valeriana officinalis by using carbon dioxide supercritical extraction method under the extraction temperature condition of less than 40℃, which specifically includes the following steps: taking valeriana officinalis medicinal material coarse powder, using carbon dioxide supercritical extraction technology, extraction temperature 30-40℃, extraction pressure 20-30MPa, the amount of entrainer is 2-4 times the weight of medicinal materials, wherein the unit of the amount of entrainer is ml and the unit of the weight of medicinal materials is g, the entrainer is selected from methanol, anhydrous ethanol or 95% ethanol, resolution temperature 30-40℃, resolution pressure 3-6MPa, CO2 flow rate 10-20L / h, extraction time 1-2h.

5. Use according to claim 3, characterized in that, The valeriana officinalis preparation is prepared by mixing and grinding valeriana officinalis volatile oil inclusion and extract powder, and its specific steps are as follows: 1) Fresh valerian rhizome and root are washed, drained and cut into 1-5 cm pieces, and then subjected to direct steam distillation under water separation and pressure, with the initial steam pressure being 0.08-0.12 mPa / cm 2 , the mid-steam pressure being 0.02-0.06 mPa / cm 2 , and the late-steam pressure being 0.08-0.10 mPa / cm 2 , for 1.5-2.5 hours, to separate volatile oil and residue; 1) Fresh valerian rhizome and root are washed, drained and cut into 1-5 cm pieces, and then subjected to direct steam distillation under water separation and pressure, with the initial steam pressure being 0.08-0.12 mPa / cm 2 , the mid-steam pressure being 0.02-0.06 mPa / cm 2 , and the late-steam pressure being 0.08-0.10 mPa / cm 2 , for 1.5-2.5 hours, to separate volatile oil and residue; 1) Fresh valerian rhizome and root are washed, drained and cut into 1-5 cm pieces, and then subjected to direct steam distillation under water separation and pressure, with the initial steam pressure being 0.08-0.12 mPa / cm 2 , the mid-steam pressure being 2) The medicinal residue is dried in advance by sun drying, oven drying or vacuum drying, is put into a percolation tank and is tamped, is soaked in 1.5 times the amount of fresh medicinal materials of 70-95% v / v ethanol for 8-12 hours, and then percolation is started, the percolation liquid is filtered and ethanol is recovered, and then is concentrated and dried to obtain valeriana officinalis dry extract, which is ground and sieved to obtain valeriana officinalis extract powder; 3) 2-5 times the weight of volatile oil of β-cyclodextrin is taken, 1-2 times the amount of distilled water is added and is ground, then valeriana officinalis volatile oil is added and is ground to fully mix and encapsulate for 20-40 minutes, water is filtered off, unencapsulated volatile oil is washed off with petroleum ether with a boiling range of 30-60℃, and then is dried, air dried or vacuum dried at room temperature, is ground and sieved to obtain valeriana officinalis volatile oil β-cyclodextrin inclusion powder; 4) The valeriana officinalis volatile oil β-cyclodextrin inclusion powder and the valeriana officinalis extract powder are mixed, starch is added to the loading amount, and then is mixed uniformly, is sieved through a 38-45 mesh sieve, and then is filled into capsules to prepare capsule preparations; the valeriana officinalis preparation is prepared from the following weight parts of raw materials: 。 6. Use according to claim 5, characterized in that, The valeriana officinalis preparation is prepared from the following weight parts of raw materials: The valeriana officinalis volatile oil is a pale yellow clear liquid with a sweet and slightly bitter taste, a relative density of 0.94-0.96, a refractive index of 1.48-1.49, and a heavy metal content of not more than 10 parts per million, and a borneol acetate content of ≥27%; The valeriana officinalis extract powder is a brownish powder with a water content of <5%, a valeriana officinalis terpene lactone A content of ≥1.3%, and a total terpene lactone content of ≥8.0%; Each capsule contains 0.29g, contains ≥40mg of valeriana officinalis volatile oil, 25±3mg of valeriana officinalis extract, >12mg of borneol acetate, >0.38mg of valeriana officinalis terpene lactone A, and >5.5mg of total terpene lactone.

7. Use according to claim 5, characterized in that, The valeriana officinalis preparation is the valeriana officinalis extract capsule of Rike® produced by Wuhan Joint Pharmaceutical Co., Ltd.