Traditional Chinese medicine composition for treating urolithiasis

Abstract

The invention provides a traditional Chinese medicine composition for treating urolithiasis. Specifically, the invention provides a traditional Chinese medicine composition consisting of glechoma longituba, semen plantaginis, pyrrosia lingua, radix achyranthis bidentatae, radix paeoniae alba, radix puerariae and honey-fried licorice root. The traditional Chinese medicine composition is simple in formula and exact in clinical curative effect. The composition is used for treating urolithiasis, can effectively relieve kidney crystallization and renal tubule injury and improve the renal function, and has the application prospect in the field of urolithiasis treatment.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating urolithiasis. Background Art

[0002] Kidney stones are a common urinary tract disease with a global prevalence of approximately 1.7-14.8%. In my country, the prevalence has exceeded 6% and is increasing. Kidney stones are a systemic disease associated with metabolic syndrome and lack effective prevention and treatment options. The formation of kidney stones increases the risk of chronic kidney disease (CKD), with a recurrence rate exceeding 50% within 5 years. Regardless of whether obstruction occurs, the renal interstitial fibrosis and renal dysfunction caused by stones continue to progress, leading to end-stage renal disease (ESRD).

[0003] Calcium oxalate (CaOx) is the most common type of kidney stone, accounting for 80-90% of cases. Modern medicine believes that kidney stones are caused by genetic and environmental factors, with the formation mechanism primarily involving the overgrowth of idiopathic Randall's spots in the kidneys and increased supersaturation of solutes, primarily calcium oxalate, in the urine. The deposition of calcium oxalate crystals in the renal interstitium is one of the key factors causing the progressive inflammation of kidney stone disease. Early in their formation, calcium oxalate crystals interact with renal parenchymal cells, triggering a damage-repair process that leads to a series of pathological processes. Oxalic acid and calcium oxalate crystals within the renal tubular lumen act on renal tubular epithelial cells, stimulating localized damage, primarily to the tubules, the production of ROS, and inflammation, which in turn causes acute and chronic kidney damage, tubulointerstitial inflammation, and interstitial fibrosis, triggering a cascade reaction that ultimately leads to the formation of kidney stones. Current treatment involves drinking plenty of water and taking medications such as citrate and thiazide diuretics, but these cannot prevent crystallization from developing into stones. Patients ultimately require surgical treatments such as extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy. Even after the stones are removed, the existing kidney damage cannot be reversed.

[0004] Currently, the most commonly used medication for urolithiasis is Compound Jinshencao Granules. Composed of Desmodium leucoderma, Plantago asiatica, Pyrrosia dahurica, and Corn Silk, Compound Jinshencao Granules primarily clear heat and dampness, promoting diuresis and stone expulsion. Clinically, it is primarily used for urinary stones and urinary tract infections characterized by damp-heat syndrome, with symptoms including frequent urination, urgency, dysuria, and low back pain, as well as urinary tract infections and urinary stones presenting with these symptoms.

[0005] The main problem with compound Centella asiatica granules is that Centella asiatica is cold in nature, Plantain is slightly cold, Selaginella ternata is bitter and cold in nature, and Corn Silk is cool in nature. Although the combination of the four medicines has a good effect in clearing away heat, it is not suitable for patients with weak spleen and stomach and prone to diarrhea. Long-term use will lead to insufficient kidney qi and is not effective in inhibiting the recurrence of stones.

[0006] Therefore, there is a need in the art to develop a new drug for treating urolithiasis. Summary of the Invention

[0007] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating urolithiasis.

[0008] In a first aspect of the present invention, a traditional Chinese medicine composition is provided, comprising or consisting of the following raw medicinal materials or extracts thereof:

[0009] 10-60 parts by weight of Herba Lycopodii;

[0010] 10-60 parts by weight of Plantago seeds;

[0011] Pyrola 10-60 parts by weight;

[0012] 3-20 parts by weight of Achyranthes bidentata;

[0013] 5-30 parts by weight of white peony root;

[0014] 10-60 parts by weight of Pueraria root;

[0015] 1-10 parts by weight of roasted liquorice root.

[0016] In another preferred embodiment, the raw medicinal materials include fresh medicinal materials, partially dried medicinal materials, dried medicinal materials or a combination thereof.

[0017] In another preferred embodiment, when the composition comprises raw medicinal materials, the weight portion thereof is calculated based on the dry weight of the corresponding raw medicinal materials.

[0018] In another preferred embodiment, when the composition comprises extracts of raw medicinal materials, the amount of the extracts is calculated based on the dry weight of the corresponding raw medicinal materials.

[0019] In another preferred embodiment, the extract includes: a water extract, an alcohol extract, an aqueous solvent extract, or a combination thereof; preferably a water extract or an alcohol extract.

[0020] In another preferred embodiment, the active ingredient includes a single ingredient or a mixed ingredient.

[0021] In another preferred embodiment, the Chinese medicine composition comprises or consists of the following raw medicinal materials or extracts thereof:

[0022] 20-40 parts by weight of Herba Lycopodii, preferably 30 parts by weight;

[0023] 20-40 parts by weight of Plantago seeds, preferably 30 parts by weight;

[0024] Pyrrosia 20-40 parts by weight, preferably 30 parts by weight;

[0025] 8-12 parts by weight of Achyranthes bidentata, preferably 10 parts by weight;

[0026] 10-20 parts by weight of white peony root, preferably 15 parts by weight;

[0027] 20-40 parts by weight of Pueraria root, preferably 30 parts by weight;

[0028] 3-9 parts by weight of roasted licorice root, preferably 6 parts by weight.

[0029] In another preferred example, in the traditional Chinese medicine composition, the weight ratio of Herba Cyperi, Plantago, Pyrifera, Achyranthes, White Peony, Pueraria, and Radix Glycyrrhizae is (1.3-2.4): (1.3-2.4): (1.3-2.4): (0.4-0.8): (0.7-1.2): (1.3-2.4): (0.2-0.5), preferably 2:2:2:0.6:1:2:0.4.

[0030] In another preferred example, the traditional Chinese medicine composition consists of 30g of Herba Cyperi, 30g of Plantago, 30g of Pyrilaria, 10g of Achyranthes, 15g of White Peony Root, 30g of Pueraria, and 6g of Radix Glycyrrhizae Preparata.

[0031] In the second aspect of the present invention, a Chinese medicine composition extractant is provided, which is prepared by extracting the Chinese medicine composition as described in the first aspect of the present invention, wherein the extraction solvent of the extractant is selected from the following group: water, ethanol and chloroform, preferably water.

[0032] In another preferred embodiment, the extractant includes an extractant with unadjusted (or unchanged) concentration, a concentrated extractant, and a diluted extractant.

[0033] In another preferred embodiment, the extractant is a decoction or extract of the traditional Chinese medicine composition.

[0034] In another preferred embodiment, the extractant is a concentrated decoction or extract.

[0035] In a third aspect of the present invention, a method for preparing the extractant of the Chinese medicine composition according to the second aspect of the present invention is provided, comprising the steps of:

[0036] a) mixing the Chinese medicine composition according to the first aspect of the present invention with 1-10 times water or an aqueous extraction solvent, and extracting for 10-60 minutes under heating conditions to obtain an extract;

[0037] b) repeating step a) 1-3 times (preferably 2 times), combining the extracts obtained each time to obtain a mixed solution;

[0038] c) optionally concentrating and / or filtering the mixed solution to obtain the extractant.

[0039] In another preferred embodiment, the decocting temperature is 100±20°C, preferably 100±10°C, and more preferably 100±5°C.

[0040] In another preferred embodiment, the extract in step a) is the supernatant, and preferably the volume ratio of the extract to water or aqueous extraction solvent is 50-150:250; preferably 80-120:250, more preferably 100:250.

[0041] In a fourth aspect of the present invention, a pharmaceutical preparation is provided, comprising:

[0042] i) the Chinese medicine composition according to the first aspect of the present invention or the extractant of the Chinese medicine composition according to the second aspect of the present invention;

[0043] ii) other pharmaceutically acceptable excipients, carriers or vehicles.

[0044] In another preferred embodiment, the pharmaceutical preparation is a traditional Chinese medicine preparation.

[0045] In another preferred embodiment, the preparation is an oral preparation or a non-oral preparation.

[0046] In another preferred embodiment, the preparation includes a liquid preparation, a semisolid preparation, or a solid preparation.

[0047] In another preferred embodiment, the preparation includes: powder, granule, capsule, mixture, powder, injection, tincture, oral solution, tablet, lozenge, or pill.

[0048] In the fifth aspect of the present invention, there is provided the use of the traditional Chinese medicine composition as described in the first aspect of the present invention, the traditional Chinese medicine composition extract as described in the second aspect of the present invention, or the pharmaceutical preparation as described in the fourth aspect of the present invention, for preparing a drug for preventing and / or treating urolithiasis or stranguria in a subject in need.

[0049] In another preferred embodiment, the prevention and / or treatment of urolithiasis includes improvement of one or more indicators selected from the following groups:

[0050] a) decrease in serum creatinine, urea nitrogen, uric acid, or a combination thereof;

[0051] b) Improve renal crystal deposition and renal tubular damage;

[0052] c) Reduce peripheral blood TNF-α and IL-6.

[0053] In another preferred embodiment, the subject is a human or non-human mammal.

[0054] In another preferred embodiment, the subject is a human, a rat or a mouse.

[0055] In another preferred embodiment, the urolithiasis is urolithiasis associated with renal insufficiency.

[0056] In another preferred embodiment, the stranguria caused by stones is of the syndrome type of kidney deficiency and bladder damp-heat.

[0057] In the sixth aspect of the present invention, a method for treating urolithiasis or stranguria is provided, comprising the steps of administering a medically effective amount of the Chinese medicine composition as described in the first aspect of the present invention or the pharmaceutical preparation as described in the fourth aspect of the present invention to a subject in need.

[0058] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] The following drawings are used to illustrate specific embodiments of the present invention and are not used to limit the scope of the present invention defined by the claims.

[0060] Figure 1 Shown are the HE staining results of mouse kidney tissue.

[0061] Figure 2 The levels of TNF-α, IL-6, IL-10, Scr, BUN, and UA in the peripheral blood of mice are shown. *p<0.05, **p<0.01Ctrl vs Caox group; #p<0.05SLF vs Caox group. DETAILED DESCRIPTION

[0062] After extensive and in-depth research, the inventors have developed a traditional Chinese medicine composition for the treatment of urolithiasis. In this formula, Herba Coptis chinensis, Plantago seed, and Selaginella dahurica clear heat and dampness, promote stranguria and expel stones, and relieve inflammation and pain. Achyranthes bidentata promotes blood circulation and menstruation, nourishing the liver and kidneys. Paeonia lactiflora, Glycyrrhiza uralensis, and Pueraria root relieve spasms and promote the passage of stones. The entire formula works together to clear heat and dampness, nourish the kidneys and activate blood circulation, relieve spasms and expel stones. The traditional Chinese medicine composition of the present invention has a streamlined formula and definite clinical efficacy. Animal experiments have demonstrated that the present formula can effectively reduce kidney crystals and tubular damage in mice with urolithiasis, and improve renal function. This is the basis for the completion of the present invention.

[0063] Compared to the existing compound herb granules of Centella asiatica, which can cause kidney deficiency with long-term use, this prescription uses the main herbs of Centella asiatica, Plantago seed, and Selaginella ternata to clear heat and dampness, relieve stranguria and expel stones, and relieve inflammation and pain. The auxiliary herb of Achyranthes bidentata nourishes the kidneys with sweetness, promotes blood circulation and menstruation, and promotes diuresis and stranguria. In addition, the adjuvant herbs of Paeonia lactiflora, Licorice root, and Pueraria root relieve spasms and relieve pain. The whole prescription clears heat, dampness, and expel stones while focusing on tonifying the kidneys and providing anti-inflammatory and antispasmodic effects. It is clinically used for patients with recurrent stones and multiple small stones. A clinical observation of 40 patients with gonorrhea with stones showed that after three months of treatment, the patients' unilateral or bilateral waist and abdominal pain, hematuria, frequent urination, urgency, and dysuria were alleviated. At the same time, symptoms of kidney deficiency such as fatigue, facial puffiness, chest tightness or irritability, dry throat, sore waist and weak knees, and dry stools also improved to varying degrees.

[0064] the term

[0065] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0066] As used herein, the terms "comprise," "include," and "contain" are used interchangeably to include not only closed definitions but also semi-closed and open definitions. In other words, the terms include "consisting of," "consisting essentially of."

[0067] As used herein, the term "pharmaceutically acceptable excipient, carrier or vehicle" refers to a substance that is suitable for use in humans and / or animals without excessive adverse side effects (such as toxicity, irritation and allergic reactions), that is, has a reasonable benefit / risk ratio.

[0068] As used herein, the term "effective amount" refers to an amount that produces a function or activity in humans and / or animals and is acceptable to humans and / or animals. Those skilled in the art will appreciate that the "effective amount" may vary depending on the form of the pharmaceutical composition, the severity of the disease, and the combination with other drugs.

[0069] The "prevention," "treatment," or "improvement" of the present invention includes delaying and stopping the progression of the disease, or eliminating the disease, and does not require 100% inhibition, elimination, or reversal. In some embodiments, the Chinese medicine composition or pharmaceutical preparation of the present invention can prevent the development of chronic glomerulonephritis, or reduce, inhibit, and / or reverse existing chronic glomerulonephritis or the symptoms thereof by, for example, at least about 10%, at least about 30%, at least about 50%, or at least about 80%, compared to the levels observed in the absence of the Chinese medicine composition or pharmaceutical preparation of the present invention.

[0070] As used herein, the terms "parts by weight" and "parts by weight" are used interchangeably. Parts by weight may be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1 mg, 1 g, 2 g, or 1 kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b may be composed of 1 gram of component a + 9 grams of component b, or 10 grams of component a + 90 grams of component b, etc. In such a composition, the percentage content of a component = (parts by weight of the component / sum of the parts by weight of all components) × 100%. Therefore, in a composition consisting of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.

[0071] As used herein, the term "raw medicinal material" refers to the Chinese medicinal material used as the active medicinal material in the compositions of the present invention. Such medicinal materials may be in various forms, including (but not limited to) dried medicinal materials, fresh medicinal materials, raw medicinal materials, cooked medicinal materials, processed medicinal materials, or combinations thereof. Furthermore, when the compositions of the present invention contain an extract of a raw medicinal material, the term also includes the raw medicinal material corresponding to the raw medicinal material extract or the corresponding raw medicinal material used to prepare the extract.

[0072] Urolithiasis

[0073] As used herein, the term "urolithiasis" is a general term for urinary stone disease, which refers to mineral crystal deposits formed in the kidney, ureter, bladder or urethra, of which kidney stones are the most common type. The stone composition is mainly calcium oxalate, followed by magnesium ammonium phosphate, uric acid and cystine. Its formation mechanism involves metabolic abnormalities (such as hypercalciuria, hyperoxaluria), urinary tract obstruction, infection or drug factors. The pathological manifestations are mechanical damage to the urinary tract mucosa by stones, obstructive hydronephrosis and secondary infection. Clinical features include lumbar and abdominal colic, hematuria and abnormal urination.

[0074] The term "urolithiasis" or "kidney stones" used in this article corresponds to the Traditional Chinese Medicine (TCM) name "stone stranguria." The "Chinese Medicine Clinical Diagnosis and Treatment Terminology: Diseases" states: "A disease characterized by low back pain, hematuria, the passage of sand and gravel, or the discovery of stones on examination is called stone stranguria." Stone stranguria is one of the five types of stranguria, and stranguria syndrome is characterized by frequent, short, and astringent urination, stinging and dripping urination, incomplete urination, lower abdominal cramps, or pain radiating to the lower back and abdomen.

[0075] The primary cause of stranguria with stones is the accumulation of damp heat, which simmers urine. Over time, these stones form, obstructing the urinary tract and causing abdominal pain. Once formed, these stones block the urinary tract, stagnating Qi flow and causing pain. Stones can also damage the meridians, leading to hematuria. Kidney deficiency leads to poor Qi transformation and frequent urination, while heat accumulation in the bladder causes difficulty in urinary flow, resulting in a dribbling, uncontrolled flow. This concept of stranguria, with kidney deficiency as the root cause and damp heat as the primary symptom, provides the theoretical foundation for stranguria. The "Zhengzhi Zhunsheng" states: "The bladder is a water organ. Severe heat generates dampness, which causes the water to become turbid and condense, resulting in stranguria... Damp heat accumulates in the lower part of the body, scorching the urine. Over time, this condenses into sand and gravel, causing stranguria with stones." The "Zhongzang Jing" states: "Deficiency damages vital qi, and pathogenic heat gradually deepens. This is like boiling salt in water with too much fire and too little water, which gradually turns the salt into stones." Therefore, later physicians generally believed that the pathogenesis of stranguria with stones is that long-term accumulation of damp heat scorches the water, causing the urine to condense. Over time, this accumulation forms sand and gravel, resulting in stranguria with stones. This is consistent with the mechanism proposed in modern medicine: urine oversaturation and crystal precipitation interact with tubular epithelial cells, forming stones.

[0076] The Chinese medicine composition of the present invention

[0077] As used herein, the terms "Chinese medicine composition of the present invention", "composition of the present invention" and "Ye's Shilin Recipe" have the same meaning, and all refer to the Chinese medicine composition for treating and / or improving urolithiasis provided by the first aspect of the present invention.

[0078] Formula Theory: Traditional Chinese Medicine (TCM) believes that stranguria has three causes: First, emotional stress, which can lead to exogenous heat, or excessive use of diuretics, which damage kidney yin, leading to yin deficiency and hyperactive fire, poor qi transformation, turbid urine, and the accumulation of deficient fire. Second, excessive sexual activity, which damages kidney yang and weakens it, weakens qi transformation, impairs the kidney's ability to open, close, and transform, and disrupts the secretion of turbid semen, preventing urine from flowing downward and depositing as stones. Third, exposure to external dampness or turbid qi, which transfers heat to the lower jiao, or excessive consumption of rich, fatty foods, generates damp heat, which accumulates in the lower jiao. Prolonged accumulation of damp heat, which condenses fluid, causes urine to condense, and eventually forms sand and gravel. According to the "Traditional Chinese Medicine Industry Standards of the People's Republic of China - Diagnosis and Efficacy Standards for TCM Diseases and Syndromes," stranguria is caused by prolonged accumulation of damp heat, which condenses urine into stones and obstructs the kidney system. Stranguria is primarily caused by damp heat, and treatment should focus on clearing heat, promoting the removal of dampness, and relieving stranguria. When using dampness-relieving agents, it's important to distinguish between upper and lower, internal and external, and examine the patient's condition, which can be characterized by cold, heat, deficiency, and excess. If dampness is located in the upper part of the body, it should be dissipated by gentle perspiration. If it is located in the lower part of the body, it should be relieved by promoting the spleen's water circulation. This is also the meaning of the "Suwen - Yin Yang Ying Xiang Da Ji" (Suwen - Yin Yang Ying Xiang Daji): "If it is located in the lower part, it should be drained." Therefore, in clinical Chinese medicine treatment, prescriptions are often formulated with the goal of invigorating Qi and activating blood circulation, clearing heat and detoxifying, softening and dispersing nodules, and promoting dampness and relieving stranguria.

[0079] Formula composition and explanation: The Yeshi Shilin prescription of the present invention contains Herba Cynanchifoliae, Plantago Seed, Selaginella Scrophulariae, Achyranthes Bidentatae, White Peony Root, Puerariae Radix, and Roasted Licorice. Among the six medicinal materials, Herba Cynanchifoliae is sweet and cool in nature, and has the effects of clearing heat and dampness, promoting diuresis and relieving stranguria, and softening and expelling stones. The heavy use of this medicine in the prescription is right on the pathogenesis; Herba Cynanchifoliae clears heat and detoxifies, and is diuretic and relieving stranguria. The "Shennong Bencao Jing" describes it as "promoting urination and removing dampness and numbness"; Selaginella Scrophulariae promotes diuresis and relieves stranguria, clears heat and cools blood; the three herbs are used together to achieve the effects of clearing heat and dampness, relieving stranguria and expelling stones, and relieving inflammation and pain, and are the main herbs. Achyranthes Bidentatae is bitter and purges, its sourness enters the liver, and its sweetness nourishes the kidneys. It is good at descending, and can activate blood circulation and unblock menstruation, nourish the liver and kidneys, promote diuresis and relieve stranguria, and guide blood downward, and is the assistant herb. Peony and Licorice are from the Shaoyao Gancao Decoction in the "Treatise on Febrile Diseases". Doctors of all dynasties have used it to treat acute symptoms of stranguria and colic, and have good efficacy. Peony is slightly acidic and neutral in nature, and is a good medicine for nourishing blood, replenishing yin and relieving spasms; licorice is sweet and slightly warm, replenishes qi and relieves urgency, and the sour and sweet transform yin; the relieving effect of licorice can be on par with peony, and the two medicines are used together and complement each other. In addition, Pueraria lobata can relieve spasms and clear stones, and can serve as an adjuvant.

[0080] Glechoma longituba (Nakai) Kupr. is the dried aerial part of the plant Huoxuedan (Huoxuedan) in the Lamiaceae family. The entire plant is used as medicine. It has a pungent, slightly bitter flavor and a slightly cold nature. It enters the liver, kidney, and bladder meridians. It promotes diuresis, relieves stranguria, clears heat and detoxifies, and disperses blood stasis and reduces swelling.

[0081] Plantago seeds are the dried mature seeds of Plantago asiatica L. or Plantago depressa Willd., both of the Plantaginaceae family. They are sweet in flavor and cold in nature. They enter the liver, kidney, lung, and small intestine meridians. They clear heat, promote diuresis, relieve stranguria, dissipate dampness, stop diarrhea, improve eyesight, and eliminate phlegm.

[0082] Pyrrosia lingua (Thunb.) Farw. is a medium-sized epiphytic fern from the Polypodiaceae family and the genus Pyrrosia. It is sweet, bitter, and slightly cold in nature. It enters the lung and bladder meridians. It promotes diuresis and relieves stranguria, clearing the lungs and relieving heat. It treats painful stranguria, hematuria, urinary tract stones, nephritis, metrorrhagia, dysentery, lung-heat cough, chronic tracheitis, wounds, and carbuncles.

[0083] Achyranthes bidentata (Achyranthes bidentata) is the dried root of Achyranthes bidentata (Achyranthes bidentata). It has a bitter, sweet, and sour flavor and is neutral. It enters the liver and kidney meridians. It removes blood stasis, tonifies the liver and kidneys, strengthens the tendons and bones, promotes urination, and relieves stranguria, promoting blood circulation.

[0084] White peony root: This is the dried root of Paeonia lactiflora Pall. (Ranunculaceae). It has a bitter, sour flavor and a slightly cold nature. It enters the liver and spleen meridians. It nourishes blood and regulates menstruation, astringes yin and stops sweating, softens the liver and relieves pain, and calms liver yang.

[0085] Pueraria root: The dried root of Pueraria montana (Lour.) Merr., a plant of the Leguminosae family. It is sweet, pungent, and cool in nature. It enters the spleen and stomach meridians. It has dispersing and relieving effects, as well as relieving spasms and pain.

[0086] Radix Glycyrrhizae Preparata is licorice root roasted with honey. Licorice root is the dried root and rhizome of the legume plants Glycyrrhiza glabra, Glycyrrhiza inflata, and Glycyrrhiza glabra. It is sweet, neutral, and non-toxic. It enters the heart and spleen meridians, and has the effects of replenishing qi and meridians, tonifying the spleen and stomach, and harmonizing the properties of other herbs.

[0087] The traditional Chinese medicine composition of the present invention focuses on tonifying the kidney and anti-inflammatory and relieving spasm while clearing away heat, promoting dampness and removing stones. Therefore, it is particularly suitable for treating stranguria caused by kidney deficiency and bladder damp-heat syndrome, which is characterized by fatigue, facial puffiness, sore waist and weak knees, and other kidney deficiency symptoms on the basis of stranguria caused by stones.

[0088] Extractant of the present invention and preparation method thereof

[0089] The present invention provides an extractant of a traditional Chinese medicine composition, wherein the extractant is prepared by extracting the traditional Chinese medicine composition of the present invention.

[0090] As used herein, the "extractant of the present invention" refers to an extract in the form of a decoction or an extract obtained by purifying the traditional Chinese medicine composition of the present invention through solvent extraction and filtration.

[0091] The active ingredients of the Chinese medicine composition of the present invention are purified by solvent extraction and filtration. The extraction method adopted can select a suitable extraction solvent and extraction conditions according to the physicochemical properties of the active ingredients in the medicine. Preferably, the extractant of the present invention is prepared by the following method:

[0092] Lianqiancao 30g, Plantago seed 30g, Pyrola 30g, Achyranthes bidentata 10g, White peony root 15g, Pueraria root 30g, Roasted licorice root 6g

[0093] Decoction method: Add 250ml of water to the first decoction, bring to a boil over high heat, then simmer for 30 minutes. Take 100ml of the juice. Add 200ml of water to the second decoction, simmer for 15 minutes, and take 100ml of the juice. Mix the two decoctions and take twice a day, morning and evening. The oral dosage is 1 bag each time, twice a day.

[0094] Preparation and administration

[0095] The present invention provides a preparation comprising Herba Lycopodii, Plantago, Pyrifera, Achyranthes, White Peony Root, Pueraria, Radix Glycyrrhizae Preparata, or extracts thereof. In the preparation, the raw medicinal materials or extracts thereof may be present in an amount of 0.1-99.9 wt%, based on the weight of the preparation. The composition may further comprise a pharmaceutically or health product-acceptable carrier.

[0096] In the present invention, it should be understood that the extract includes not only the concentrated solution (such as an extract) or active ingredient (such as a powder) obtained by extracting the raw medicinal materials, but also the concentrated solution (such as an extract) or active ingredient mixture obtained by extracting a single medicinal material from the raw medicinal materials (including the mixture of concentrated solutions, active ingredients, or concentrated solutions). The active ingredient of the raw medicinal materials includes a single ingredient or a mixture of ingredients.

[0097] There are no particular limitations on the dosage form of the preparation of the present invention, and any dosage form suitable for mammals may be used. Preferably, the dosage form may include tablets, capsules, granules, pills, mixtures, powders, oral liquids, buccal tablets, or aerosols. From the perspective of ease of preparation, administration, or consumption, the preferred composition is a liquid formulation. Oral administration is preferred.

[0098] The preparations of the present invention may be added with various conventional carriers and / or excipients required for preparing different dosage forms. The excipients described herein are pharmaceutically acceptable excipients and include dextrin, lactose, sodium bicarbonate, citric acid, sodium hydroxymethyl starch, micropowdered silica gel, starch, soluble starch, polyethylene glycol, or magnesium stearate. Conventional methods for preparing traditional Chinese medicines may be used to prepare the preparations into any commonly used dosage form, such as tablets, capsules, granules, capsules, pills, and powders.

[0099] Some examples of pharmaceutically acceptable excipients include cellulose and its derivatives (such as methyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerol, mannitol, sorbitol, etc.), emulsifiers (such as Tween), wetting agents (such as sodium lauryl sulfate), buffers, chelating agents, thickeners, pH regulators, transdermal enhancers, colorants, flavorings, stabilizers, antioxidants, preservatives, antibacterial agents, pyrogen-free water, etc.

[0100] The preparation of the present invention can avoid the temporary boiling of Chinese herbal decoctions before taking, which is prone to mildew and deterioration when left for a long time and brings a lot of inconvenience to patients. According to the characteristics of clinical medication, the physical and chemical properties of the main medicinal flavors in the prescription are preserved, and modern preparation technology is combined to prepare solid preparations such as granules, tablets, capsules, powders, etc., which can conveniently and effectively meet the needs of patients.

[0101] The preparation of the present invention can be directly used to prepare a medicament for preventing and / or treating chronic kidney disease. The preparation of the present invention may also contain other optional medicinal materials or extracts thereof, or other drugs effective for treating and / or preventing chronic kidney disease. Preferably, the preparation of the present invention can alleviate symptoms such as proteinuria, hematuria, backache, and nocturia caused by chronic kidney disease.

[0102] Typically, the formulations of the present invention are administered daily at a dose of 0.001-20 g / kg of animal body weight, preferably in 1-4 divided doses per day, or in a sustained-release form. For most mammals, the total daily dose is 0.05-600 g. Of course, the specific dosage will vary depending on the mode of administration, dosage form, and severity of the disease being treated, and the route of administration is within the skill of the skilled physician. Administration can be by conventional routes, including, but not limited to, oral, intramuscular, transdermal, or topical administration. Oral administration is preferred.

[0103] The present invention also provides a method for preventing and / or treating chronic kidney disease, comprising administering the composition or formulation of the present invention to a subject in need thereof. The subject may be a human or a non-human mammal (e.g., a dog, pig, cat, monkey, sheep, horse, cattle, etc.).

[0104] The main advantages of the present invention include:

[0105] 1) The Chinese medicine composition of the present invention has definite efficacy and high safety;

[0106] 2) The preparation method of the Chinese medicine composition of the present invention is simple, low-cost, and the raw materials are readily available;

[0107] 3) The Chinese medicine composition of the present invention can reduce renal crystal deposition, improve renal function, and alleviate inflammatory response in an animal model of calcium oxalate kidney stones, and the effect is better than the commercially available compound Lysimachia granules.

[0108] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989), or according to the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight.

[0109] The quality of the Chinese medicinal materials involved in the present invention all complies with the relevant regulations under the corresponding medicinal materials in Part I of the Chinese Pharmacopoeia 2010 edition.

[0110] Example 1 Clinical Trial

[0111] 1. Formula

[0112] Ye’s prescription for treating stranguria: 30g of Coptis chinensis, 30g of Plantago seed, 30g of Selaginella ovata, 10g of Achyranthes bidentata, 15g of White Peony Root, 30g of Pueraria lobata, and 6g of roasted Licorice root.

[0113] Take one dose daily, decoct in water and take twice. One course of treatment is 4 weeks.

[0114] Formula composition: Coptis chinensis, Plantago seed, and Selaginella ternata in the formula clear heat and dampness, dissipate stranguria and expel stones, and relieve inflammation and pain; Achyranthes bidentata promotes blood circulation and menstruation, nourishing the liver and kidneys; Peony root, Licorice root, and Pueraria root relieve spasms and dissipate stones. The entire formula works together to clear heat and dampness, nourish the kidneys, activate blood circulation, and relieve spasms and expel stones.

[0115] 2. Experimental Methods

[0116] 2.1 Experimental Grouping

[0117] 81 patients with kidney stones were divided into two groups. The Yeshi Shilin Fang group (40 cases) was treated with oral Yeshi Shilin Fang combined with drinking plenty of water (more than 2L per day). The control group (41 cases) was treated with drinking plenty of water (more than 2L per day) for 12 weeks. The clinical efficacy of the patients was observed.

[0118] 2.2 Criteria for determining efficacy:

[0119] It was formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" and the "Clinical Disease Diagnosis Based on Cure and Improvement Standards" issued by the Ministry of Health of the People's Republic of China (Sun Chuanxing. Clinical Disease Diagnosis Based on Cure and Improvement Standards - 2nd Edition. People's Military Medical Publishing House, 1998.).

[0120] ⑴Basis for evaluating the efficacy of TCM syndromes

[0121] ① Clinical cure: Clinically cured, clinical symptoms and signs of TCM disappear or basically disappear, and the syndrome score is reduced by ≥95%.

[0122] ② Markedly effective: Clinical symptoms and signs of TCM were significantly improved, and the syndrome score was reduced by ≥70%.

[0123] ③Effective: TCM clinical symptoms and signs are improved, and the syndrome score is reduced by ≥30%.

[0124] ④ Ineffective: There is no significant improvement in TCM clinical symptoms and signs, or they may even worsen, and the symptom score decreases by less than 30%.

[0125] Note: Calculation formula (nimodipine method) is: [(score before treatment - score after treatment) ÷ score before treatment] × 100%

[0126] ⑵Basis for comprehensive efficacy evaluation

[0127] ① Cured: Clinical symptoms and signs disappear, proving that the stone has been expelled; or, although no stone specimen has been collected, clinical symptoms and signs disappear, and ultrasound examination shows that the stone has disappeared; or hydronephrosis disappears; or urine calcium / creatinine decreases by 10%; or blood creatinine and urea nitrogen remain normal / decrease by more than 20% compared with the original level;

[0128] ② Effective: Clinical symptoms and signs disappear, B-ultrasound examination shows that the stone has shrunk by more than 30%; or it has moved downward by more than 3 cm, and hydronephrosis has disappeared; or there is obvious stone fragmentation and dissolution; or the concurrent urinary tract infection is significantly alleviated or urine calcium / creatinine decreases by 5%; or blood creatinine and urea nitrogen remain normal or decrease by 10-20% compared with the original level;

[0129] ③ Ineffective: No improvement in clinical symptoms and signs, no change in stones on ultrasound examination; or no improvement in hydronephrosis and obstruction; or urine calcium / creatinine decreases by <5%; or blood creatinine and urea nitrogen remain normal / decrease by <10% compared with the original level.

[0130] 3. Experimental Results

[0131] In the Ye Shi Lin Fang group, 40 patients were treated with the formula: 19 were cured, 5 were effective, and 16 were ineffective, for an effective rate of 77.5%. In the control group, 41 patients were treated with the formula: 16 were cured, 4 were effective, and 21 were ineffective, for an effective rate of 56.1%. The difference between the two groups was statistically significant (P < 0.05). This study demonstrates that the Ye Shi Lin Fang formula is highly effective in treating kidney stones.

[0132] Example 2 Animal Test

[0133] 1. Experimental Plan

[0134] (1) Experimental animals and husbandry: 40 SPF male ICR mice, 6-7 weeks old, weighing 25-30 g, were housed in the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine.

[0135] (2) Establishment of a calcium oxalate crystallization mouse model: The normal control group was fed a standard breeding diet (P1101F). The model group mice were fed a high-oxalate diet, prepared by adding sodium oxalate (50 μmol / g) to a nearly calcium-free diet (TD.95027). All mice had free access to water for 14 days.

[0136] (3) Drug Intervention: Calculated according to Xu Shuyun's "Pharmacological Experimental Methodology," a dose of 9 times the adult dose per kg body weight was administered orally. Ye's Shilin Formula (30 ml / kg) was administered orally. Compound Qianshencao Granules (1.35 g / kg body weight) were dissolved in water and administered orally to mice. The remaining mice were given an equal volume of normal saline by gavage once daily for 14 consecutive days.

[0137] (4) Experimental groups: 40 SPF male ICR mice, 6-7 weeks old, weighing 25-30 g, were fed a conventional breeding feed for one week and then randomly divided into the following 4 groups, 6 mice in each group:

[0138]

[0139] 5. Specimen collection: After the experiment, mice were anesthetized with sodium thiopental and 1 mm of renal tissue was collected from the cortical medullary junction. 3 After rinsing with saline, the specimens were fixed in 2.5% glutaraldehyde fixative for electron microscopy. Blood was collected from the orbital cavity and serum was collected for analysis. After cardiac perfusion, the right kidney was immediately removed and stored at -80°C for nucleic acid and protein analysis. The left kidney was fixed in 10% paraformaldehyde for histopathological examination.

[0140] 2. Experimental Results

[0141] The renal tissue pathological changes of mice in each group were observed, and the peripheral blood tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were detected.

[0142] HE staining results showed that there was no obvious pathological change in the tubular interstitium of the blank control group mice, while crystal deposition and tubular damage were found in the model group. The tubular damage and crystal deposition were improved after treatment with Compound Centella asiatica and Ye's Shilin Decoction. The improvement of crystal deposition after treatment with Ye's Shilin Decoction was better than that after treatment with Compound Centella asiatica ( Figure 1 ).

[0143] The peripheral blood TNF-α, IL-6, Scr, BUN and UA of the mice in the model group were significantly higher than those in the blank control group and the Yeshi Shilin prescription group, and the differences were statistically significant ( Figure 2 The serum IL-10 level of mice in the model group was lower than that in the blank control group and the Yeshi Shilin prescription group, and the difference was statistically significant ( Figure 2 ).

[0144] 3. Experimental Conclusion

[0145] The prescription of the present invention can protect the kidney tissue of calcium oxalate kidney stone model mice, reduce renal crystal deposition, improve renal function, and alleviate inflammatory response, and the effect is better than that of compound Lysimachia chinensis granules.

[0146] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A Chinese medicine composition, characterized in that The Chinese medicine composition comprises the following raw medicinal materials or extracts thereof, or is composed of the following: 10-60 parts by weight of Herba Lycopodii; 10-60 parts by weight of Plantago seeds; Pyrola 10-60 parts by weight; 3-20 parts by weight of Achyranthes bidentata; 5-30 parts by weight of white peony root; 10-60 parts by weight of Pueraria root; 1-10 parts by weight of roasted liquorice root.

2. The Chinese medicine composition according to claim 1, wherein The Chinese medicine composition comprises the following raw medicinal materials or extracts thereof, or is composed of the following: 20-40 parts by weight of Herba Lycopodii; 20-40 parts by weight of Plantago seeds; Pyrrosia 20-40 parts by weight; 8-12 parts by weight of Achyranthes bidentata; 10-20 parts by weight of white peony root; 20-40 parts by weight of Pueraria root; 3-9 parts by weight of roasted liquorice root.

3. The Chinese medicine composition according to claim 1, wherein In the traditional Chinese medicine composition, the weight ratio of Herba Lycopodii, Semen Plantaginis, Pyrrosiae Rhizoma, Achyranthes Bidentatae, Paeonia lactiflora, Puerariae Root and Radix Glycyrrhizae is (1.3-2.4): (1.3-2.4): (1.3-2.4): (0.4-0.8): (0.7-1.2): (1.3-2.4): (0.2-0.5).

4. An extractant for a Chinese medicine composition, which is prepared by extracting the Chinese medicine composition according to claim 1, wherein the extraction solvent of the extractant is selected from the group consisting of water, ethanol and chloroform.

5. The Chinese medicine composition extractant according to claim 4, characterized in that The extractant is the decoction or extract of the traditional Chinese medicine composition.

6. A method for preparing the extractant of the Chinese medicine composition according to claim 4, comprising the steps of: a) mixing the Chinese medicine composition according to claim 1 with 1-10 times of water or an aqueous extraction solvent, and extracting for 10-60 minutes under heating conditions to obtain an extract; b) repeating step a) 1-3 times, combining the extracts obtained each time to obtain a mixed solution; c) optionally concentrating and / or filtering the mixed solution to obtain the extractant.

7. A pharmaceutical preparation comprising: i) the Chinese medicine composition according to claim 1 or the extract of the Chinese medicine composition according to claim 4; ii) other pharmaceutically acceptable excipients, carriers or vehicles.

8. Use of the traditional Chinese medicine composition according to claim 1, the traditional Chinese medicine composition extract according to claim 4, or the pharmaceutical preparation according to claim 7 for preparing a medicament for preventing and / or treating urolithiasis or stranguria in a subject in need thereof.

9. The use according to claim 8, characterized in that The prevention and / or treatment of urolithiasis includes improving one or more indicators selected from the following group: a) decrease in serum creatinine, urea nitrogen, uric acid, or a combination thereof; b) Improve renal crystal deposition and renal tubular damage; c) Reduce peripheral blood TNF-α and IL-6.

10. The use according to claim 8, characterized in that The stranguria caused by stranguria is a syndrome of kidney deficiency and bladder damp-heat.

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