Pharmaceutical composition for treating chronic kidney disease

Abstract

The invention provides a pharmaceutical composition for treating chronic kidney disease. The invention also provides a preparation method of the pharmaceutical composition. The invention further provides a traditional Chinese medicine preparation. The invention further provides a traditional Chinese medicine pill and a preparation method thereof. The invention further provides application of the pharmaceutical composition, the traditional Chinese medicine preparation or the traditional Chinese medicine pill in preparation of medicines for treating chronic kidney diseases. The pharmaceutical composition for treating chronic kidney disease provided by the invention can reduce proteinuria, improve kidney circulation, regulate blood fat, protect renal functions, improve anemia and malnutrition of patients with CKD, especially DKD, and reduce the incidence rate of end-stage renal failure.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and relates to a pharmaceutical composition for treating chronic kidney disease, and specifically relates to a pharmaceutical composition for treating chronic kidney disease, a traditional Chinese medicine pill, and a preparation method and use thereof. Background Art

[0002] Chronic kidney disease (CKD) and the uremia caused by it are common clinical diseases and one of the most difficult to treat diseases so far. They are the third killer after cardiovascular and cerebrovascular diseases and tumors. Among primary kidney diseases, the most common is chronic glomerulonephritis, followed by tubular and interstitial diseases; among secondary kidney diseases, diabetic nephropathy ranks first, followed by hypertensive renal damage. Among them, diabetic kidney disease (DKD) is a chronic kidney disease caused by diabetes. Due to its severe microvascular complications, it causes glomerular sclerosis and renal interstitial fibrosis, which is an important cause of the development of end-stage renal failure. At present, diabetic nephropathy (DKD) generally takes only 5-10 years to progress to end-stage renal failure (ESRD). Patients need long-term dialysis to maintain their lives, and the mortality rate also increases significantly. Dialysis treatment is used, but the cost of dialysis treatment is a "catastrophic expenditure" for most patient families. Due to the limited protection of the existing medical insurance system, it often causes the phenomenon of "poverty caused by illness" and "poverty caused by illness". Therefore, early prevention and treatment of diabetic nephropathy (DKD) has become a major topic in clinical research, and research on delaying the progression of chronic kidney disease is of great significance. Summary of the invention

[0003] In view of the shortcomings of the prior art described above, the object of the present invention is to provide a pharmaceutical composition for treating chronic kidney disease, which has a rigorous formulation, scientific compatibility, and can maximize the efficacy of the drug. The preparation steps and conditions of the pharmaceutical composition and its Chinese medicine pills are optimized, which can reduce proteinuria, improve renal circulation, regulate blood lipids, protect renal function, improve anemia and malnutrition in CKD, especially DKD patients, and reduce the incidence of end-stage renal failure.

[0004] To achieve the above-mentioned object and other related objects, the first aspect of the present invention provides a pharmaceutical composition for treating chronic kidney disease, comprising the following raw material components by weight:

[0005] 10-50 parts by weight of Astragalus;

[0006] 5-30 parts by weight of Cordyceps sinensis;

[0007] 3-15 parts by weight of Taxus chinensis;

[0008] 3-15 parts by weight of Panax notoginseng;

[0009] 5-30 parts by weight of wolfberry;

[0010] 10-25 parts by weight of cooked polygonatum;

[0011] 5-30 parts by weight of Ganoderma lucidum;

[0012] 10-25 parts by weight of Pueraria root;

[0013] Gynostemma pentaphyllum 10-30 parts by weight;

[0014] Sophora flavescens 10-25 parts by weight;

[0015] Eucommia ulmoides 5-20 parts by weight;

[0016] 3-15 parts by weight of Curcuma zedoaria;

[0017] 10-50 parts by weight of Rhizoma Smilacis Glabrae;

[0018] 5-30 parts by weight of cooked rhubarb;

[0019] 5-30 parts by weight of Serissa rutinae;

[0020] 5-20 parts by weight of Ligusticum chuanxiong.

[0021] The second aspect of the present invention provides a method for preparing a pharmaceutical composition for treating chronic kidney disease, comprising: crushing each raw material component of the pharmaceutical composition described in the first aspect of the present invention into raw material powders respectively, sieving them, and then mixing them according to a ratio to provide the pharmaceutical composition.

[0022] The third aspect of the present invention provides a traditional Chinese medicine preparation, comprising a therapeutically effective amount of the pharmaceutical composition provided by the first aspect of the present invention, and one or more conventional pharmaceutically acceptable excipients.

[0023] The fourth aspect of the present invention provides a traditional Chinese medicine pill, comprising a therapeutically effective amount of the pharmaceutical composition provided by the first aspect of the present invention.

[0024] The fifth aspect of the present invention provides a method for preparing a Chinese medicine pill, comprising: adding the pharmaceutical composition provided in the first aspect of the present invention to auxiliary materials for mixing and pilling, drying, and screening to provide the Chinese medicine pill.

[0025] The sixth aspect of the present invention provides the use of the pharmaceutical composition provided in the first aspect of the present invention, the traditional Chinese medicine preparation provided in the third aspect of the present invention, or the traditional Chinese medicine pill provided in the fourth aspect of the present invention in the preparation of a medicament for treating chronic kidney disease.

[0026] As described above, a pharmaceutical composition for treating chronic kidney disease provided by the present invention can significantly improve the clinical symptoms of patients with DKD kidney deficiency turbidity and stasis syndrome in combination with conventional basic treatment, reduce the DD and FDA levels of patients with DKD kidney deficiency turbidity and stasis syndrome, improve blood circulation, reduce 24hUTP, UACR, Cys-C, BUN, UA, Scr levels, protect the kidneys, improve the levels of TCH, TG, and LDL, regulate blood lipids, improve the patient's Hb, RBC, Alb, improve anemia and malnutrition, and delay the process of DKD development to end-stage renal failure. In the 24-month follow-up, the party can reduce the cumulative risk rate of the composite endpoint of the kidney, significantly reduce UACR, and the effect is continuous. It reduces proteinuria, improves renal circulation, regulates blood lipids, protects renal function, improves anemia and malnutrition in DKD patients, reduces the incidence of end-stage renal failure, protects renal function, and reduces kidney damage, and then plays a role in protecting the kidneys and delaying the process of chronic renal failure, improves the clinical efficacy of conventional basic treatment, and also provides a theoretical basis for further clinical promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Shown is a curve chart comparing the risk rates of the composite renal endpoint between the two groups after 24 months of follow-up.

[0028] Figure 2 Shown is a comparative curve of UACR between the two groups after 24 months of follow-up. DETAILED DESCRIPTION

[0029] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are intended to describe specific embodiments, rather than to limit the scope of protection of the present invention. The test methods in the following examples without specifying specific conditions are generally carried out under conventional conditions or under conditions recommended by the manufacturers.

[0030] The first aspect of the present invention provides a pharmaceutical composition for treating chronic kidney disease, comprising the following raw material components by weight:

[0031] 10-50 parts by weight of Astragalus; specifically 10-20 parts, 20-40 parts, 40-50 parts;

[0032] 5-30 parts by weight of Cordyceps sinensis; specifically 5-10 parts, 10-20 parts, 20-30 parts;

[0033] 3-15 parts by weight of Taxus chinensis; specifically 3-6 parts, 6-12 parts, 12-15 parts;

[0034] 3-15 parts by weight of Panax notoginseng; specifically 3-6 parts, 6-12 parts, 12-15 parts;

[0035] 5-30 parts by weight of wolfberry; specifically 5-10 parts, 10-20 parts, 20-30 parts;

[0036] 10-25 parts by weight of cooked polygonatum; specifically 10-16 parts, 16-20 parts, 20-25 parts;

[0037] 5-30 parts by weight of Ganoderma lucidum; specifically 5-10 parts, 10-20 parts, 20-30 parts;

[0038] 10-25 parts by weight of Pueraria root; specifically 10-16 parts, 16-20 parts, 20-25 parts;

[0039] Gynostemma pentaphyllum 10-30 parts by weight; specifically 10-15 parts, 15-25 parts, 25-30 parts;

[0040] Sophora flavescens 10-25 parts by weight; specifically 10-16 parts, 16-20 parts, 20-25 parts;

[0041] Eucommia ulmoides 5-20 parts by weight; specifically 5-10 parts, 10-14 parts, 14-20 parts;

[0042] 3-15 parts by weight of Curcuma zedoaria; specifically 3-6 parts, 6-12 parts, 12-15 parts;

[0043] 10-50 parts by weight of Smilax glabra; specifically 10-20 parts, 20-40 parts, 40-50 parts;

[0044] 5-30 parts by weight of cooked rhubarb; specifically 5-10 parts, 10-20 parts, 20-30 parts;

[0045] 5-30 parts by weight of Serissa ruthenium; specifically 5-10 parts, 10-20 parts, 20-30 parts;

[0046] 5-20 parts by weight of Ligusticum chuanxiong; specifically 5-10 parts, 10-14 parts, 14-20 parts.

[0047] In the present invention, the astragalus is the dried root of the leguminous plant Astragalus mongolica or Astragalus membranaceus, which has the effects of invigorating qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting body fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and discharging pus, and healing sores and promoting tissue regeneration.

[0048] In the present invention, the Cordyceps sinensis is the spore stalk bundle of the ergot fungus Cordyceps sinensis, or the dried fruiting body of Cordyceps sinensis and the dried parasite body thereof, which has the effects of dispersing wind-heat, calming nerves and relieving spasms.

[0049] In the present invention, the cooked yew is the processed powder of yew. The yew is the root, stem, leaf, fruit and seed of the genus Taxus of the Taxaceae family, and has the effects of diuresis, detumescence, warming the kidney and promoting menstruation.

[0050] In the present invention, the Panax notoginseng is the dried root and rhizome of Panax notoginseng of the Araliaceae family, which has the effects of dispersing blood stasis, stopping bleeding, reducing swelling and relieving pain.

[0051] In the present invention, the wolfberry is the dried mature fruit of the Ningxia wolfberry of the Solanaceae family, which has the effects of nourishing the liver and kidneys and improving vision.

[0052] In the present invention, the cooked polygonatum is the processed powder of polygonatum. The polygonatum is the dried rhizome of Yunnan polygonatum, polygonatum or multiflorum polygonatum of the lily family, which has the effects of replenishing qi and nourishing yin, strengthening spleen, moistening lung and benefiting kidney.

[0053] In the present invention, the ganoderma lucidum is the dried fruiting body of the Ganoderma lucidum or Ganoderma rubrum of the Polyporaceae family, and has the effects of replenishing qi, calming the mind, relieving cough and relieving asthma.

[0054] In the present invention, the kudzu root is the dried root of the leguminous plant kudzu, which has the effects of relieving muscles and reducing fever, promoting body fluid, clearing rashes, and raising yang and stopping diarrhea.

[0055] In the present invention, the Gynostemma pentaphyllum is the whole herb of Gynostemma pentaphyllum, a plant of the genus Gynostemma of the Cucurbitaceae family, and has the effects of invigorating qi and strengthening the spleen, resolving phlegm and relieving cough, and nourishing the heart and calming the mind.

[0056] In the present invention, the sophora flavescens is the dried root of the leguminous plant sophora flavescens, which has the effects of clearing away heat and dampness, killing insects and promoting diuresis.

[0057] In the present invention, the eucommia bark is the dried bark of the eucommia plant of the Eucommia family, which has the effects of nourishing the liver and kidney, strengthening the tendons and bones, and calming the fetus.

[0058] In the present invention, the zedoary turmeric is the dried rhizome of the zingiberaceae plant zedoary turmeric, zedoary turmeric or zedoary turmeric, which has the effects of promoting qi and removing blood, eliminating accumulation and relieving pain.

[0059] In the present invention, the Chinese smilax glabra is the dried rhizome of the lily family plant Smilax glabra, which has the effects of detoxification, dehumidification and joint unblocking.

[0060] In the present invention, the cooked rhubarb is the processed powder of rhubarb. The rhubarb is the dried root and rhizome of Rheum palmatum, Rheum tanguticum or Rheum officinale of the Polygonaceae family, which has the effects of purging and attacking accumulation, clearing away heat and purging fire, cooling blood and detoxifying, removing blood stasis and promoting menstruation, and removing dampness and relieving jaundice.

[0061] In the present invention, the radix seu ruticosae is the dried whole plant of the radix seu ruticosae of the Rubiaceae family, and has the effects of dispelling wind and relieving exterior symptoms, clearing away heat and removing dampness, and relaxing muscles and activating collaterals.

[0062] In the present invention, the chuanxiong is the dried rhizome of the umbelliferae plant chuanxiong, which has the effects of promoting blood circulation, promoting qi, dispelling wind and relieving pain.

[0063] The above-mentioned raw materials (or medicinal materials) used in the present invention can be purchased from ordinary medical stores or Chinese medicinal material sales companies. Their specifications meet national medical standards or meet relevant regulations such as the Chinese Pharmacopoeia, and are all included in the national catalog of medicinal and edible products.

[0064] The pharmaceutical composition for treating chronic kidney disease prepared in the present invention fully follows the principle of syndrome differentiation and treatment in traditional Chinese medicine. Based on the theory of "mediation of the triple energizer to treat the kidney" by Professor Chen Yiping, a famous Chinese medicine doctor in Shanghai, Professor Chen proposed that if the triple energizer is blocked, the qi disease is the first. The kidney stores the original qi, the root of life, and the source of yang qi, all of which use the triple energizer as a channel, connecting the meridians externally and the internal organs internally. If various causes such as congenital or acquired damage the kidney's qi, blood, yin and yang, and the triple energizer qi is blocked, there will be imbalance of the nutrient and defense, disharmony of the internal organs, and blockage of the upper and lower, internal and external, and meridians, so that the qi, blood, and body fluids are lost and stagnant, and dampness, turbidity, and blood stasis appear internally. We found that DKD is mostly caused by congenital deficiency, or long-term illness, which damages the kidney essence. Clinically, it is often seen as premature aging, weakness in the waist and knees, stooped body, unsteady gait, dizziness, blurred vision, forgetfulness or amnesia, or accompanied by hearing loss and deafness. If it is not treated properly, the disease will progress, dampness, turbidity and evil will accumulate, blocking the qi mechanism, causing abnormal rise and fall, and dysfunction of the decision and drainage. Nausea and vomiting, dry mouth and bitter mouth, or sticky mouth, heaviness and drowsiness, abdominal distension, long-term illness and blood stasis, which leads to qi and blood stagnation, heaviness and soreness of limbs, purple lips, or blood stasis and heat, septicemia, blood movement, and mixed syndromes of deficiency and excess such as wind, phlegm, water and dampness. Deficiency of kidney essence is the cause of DKD. Over time, the disease lingers, gradually causing stasis and turbidity due to deficiency; stasis and turbidity are both pathological results and new treatment factors, further aggravating the deficiency of kidney essence. From the complex and diverse syndromes of DKD, we differentiate the core element of kidney deficiency and blood stasis, and adopt the method of tonifying the kidney, removing blood stasis and lowering turbidity for prevention and treatment. We focus on tonifying the kidney and nourishing the essence with the "triple energizer of location", on invigorating qi and activating blood circulation with the "triple energizer of function", and on removing dampness and lowering turbidity with the "triple energizer of channel", achieving very good therapeutic effects.

[0065] Specifically, the formula is explained as follows: The kidney stores essence, controls bones and produces marrow, and is the foundation of the innate constitution; the liver stores blood, controls tendons and is the general's organ. Essence and blood can be transformed into each other, and deficiencies in liver and kidney yin and blood can often affect each other. The brain is the sea of ​​marrow. Insufficient kidney yin cannot produce marrow to fill the brain. Insufficient liver blood cannot nourish the head and eyes, resulting in dizziness, tinnitus, and blurred vision. Water and fire are not in harmony, and the ruler and minister fire is strong, rushing upward along the meridians, causing stagnation of qi and blood, resulting in restlessness and insomnia. Yin cannot support yang, so yang qi floats excessively and body fluids are not distributed, resulting in hot muscles and red face, thirst and thirst. The waist is the home of the kidneys. Fatigue and internal injuries cause kidney yin deficiency, insufficient bone marrow, and poor nourishment to the waist. Insufficient liver blood causes poor moisture in the tendons and veins, resulting in soreness, weakness, and dull pain in the ribs. Insufficient yin and excessive yang cause the kidneys to fail to open and close, and qi transformation is dysfunctional. The essence of water and grain cannot be distributed to the four sides, but is instead transported to the bladder, causing frequent urination and turbid urine. Water and grain are transformed into water but not essence, and fluids flow downward, causing stasis in the meridians, resulting in edema of the lower limbs. The intestines are not moistened, conduction is poor, and the stool is dry and hard. The tongue is red or dark red, with a thin white or scanty coating, and a deep, thready or weak pulse. It is mainly used to treat symptoms of kidney deficiency with a mixture of dampness, turbidity and blood stasis.

[0066] Among them, the principles of monarch, minister, assistant and envoy are as follows:

[0067] Astragalus, Cordyceps sinensis, Red Ganoderma Lucidum, and Polygonatum sibiricum are the main drugs. Astragalus is sweet and warm in nature. It has the effects of replenishing qi and generating blood, making qi prosperous and blood generating, and stopping the deficiency heat by itself. It is a great invigorating qi of the spleen and lungs, and it is used to transform the source and make qi prosperous and blood generating. Cordyceps sinensis is cold in nature and sweet in taste. It has the effects of tonifying the kidney and lungs, and harmonizing the Ying and Wei. It and Astragalus are warm and cool, which can benefit the kidney essence, restrain the lung qi, and harmonize the Ying and Wei. Then the floating yang is restrained, the yang is generated and the yin is long, the qi is prosperous and blood is generated, and the deficiency heat is self-reduced. Red Ganoderma Lucidum is flat in nature and sweet in taste. It belongs to the heart meridian, lung meridian, liver meridian, and kidney meridian. It has the effects of replenishing qi and calming the mind, nourishing the liver and benefiting the essence. It can help Astragalus replenish qi and help Cordyceps sinensis calm the mind and benefit the essence. Cooked Polygonatum sibiricum is flat in nature and sweet in taste. It belongs to the spleen, lung, and kidney meridians. It has the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lungs, and benefiting the kidneys. The four drugs are the main drugs together, which play the effects of replenishing qi and blood of the five internal organs, replenishing deficiency, benefiting essence, and relieving deficiency heat.

[0068] The cooked yew, Gynostemma pentaphyllum, Eucommia ulmoides, and Lycium barbarum are the assistant drugs. The cooked yew is sweet and flat, and it enters the kidney and heart meridians. It has the functions of reducing swelling and dispersing knots, promoting menstruation and promoting diuresis, and can help Astragalus membranaceus to promote qi and promote water and reduce swelling. Gynostemma pentaphyllum is slightly sweet and cool in nature, and it enters the lung, spleen, and kidney meridians; it has the functions of invigorating qi and strengthening spleen, clearing away heat and detoxifying, and is mainly used to treat physical weakness, fatigue, and loss of semen, and can help Ganoderma lucidum to protect the liver and benefit the kidney. Eucommia ulmoides is sweet and warm in nature, and it has the functions of nourishing the liver and kidney, strengthening tendons and bones, and regulating Chong and Ren. Lycium barbarum is sweet and flat in nature, and it enters the liver and kidney meridians. Eucommia ulmoides and Lycium barbarum are both the most commonly used traditional Chinese medicines for tonifying the liver and kidney. The four medicines can help the main medicine to disperse knots and reduce swelling, and nourish the liver and kidney.

[0069] Panax notoginseng, Curcuma zedoaria, Pueraria root, and Chuanxiong are adjuvants. Panax notoginseng is warm in nature, sweet and slightly bitter in taste, and enters the liver and stomach meridians. It has the effects of dispersing blood stasis, stopping bleeding, reducing swelling and relieving pain. Curcuma zedoaria is warm in nature, pungent and bitter in taste, and enters the liver and spleen meridians; it has the functions of promoting qi and relieving depression, removing blood stasis, and relieving pain. Chuanxiong is warm in nature, pungent in taste, and enters the liver, gallbladder, and pericardium meridians. It has the effects of promoting blood circulation and removing blood stasis, promoting qi and relieving depression, and removing wind and relieving pain. The combination of the three medicines enhances the effect of promoting blood circulation and removing blood stasis. Pueraria root is cool in nature, sweet and pungent in taste; it enters the spleen meridian and stomach meridian; it has the functions of relieving muscle and fever, promoting body fluid, and raising yang qi, and can help Astragalus membranaceus to raise yang, relieve muscle heat and red face, and thirst and drink; it helps Panax notoginseng, Curcuma zedoaria, and Chuanxiong to promote blood circulation and remove blood stasis, and the cool nature of Pueraria root can relieve the warm and hot nature of the three medicines. The four medicines are collectively adjuvant medicines, assisting the main medicine in nourishing the liver and kidneys, promoting qi and relieving depression, activating blood circulation and unblocking meridians, and removing stagnation and lowering turbidity.

[0070] Smilax glabra, Sophora flavescens, Psoralea corylifolia, and Rhubarb are the guiding drugs. Smilax glabra is flat in nature, sweet and light in taste, and has the effects of detoxification, dehumidification, and joint unblocking. Sophora flavescens is cold in nature, bitter in taste, and enters the liver, kidney, stomach, and large intestine meridians, and has the effects of clearing heat and dampness, promoting diuresis and dispelling wind. Psoralea corylifolia is cool in nature, light in taste, and slightly pungent, and has the effects of soothing the liver and relieving depression, clearing heat and promoting dampness, and reducing swelling and removing toxins. Rhubarb is bitter in taste, cold in nature, and enters the stomach, spleen, large intestine, liver, and heart meridians; it has the effects of purging heat and relieving constipation, purging fire and detoxifying. The four drugs are guiding drugs, which are good at descending and draining, and can lead the drugs downward. They can treat diabetes, urination difficulties caused by damp heat in the lower part of the body, and red and astringent urine, and can make all drugs normally transport and transform through the spleen, stomach, and intestines to exert their medicinal effects.

[0071] The above sixteen medicines are used together and compatible with each other to play their synergistic therapeutic effects. The whole formula has both tonifying and purging effects, the tonifying does not hurt the yin, the purging does not hurt the body, it strengthens the body and eliminates evil, takes into account both the symptoms and the root cause, and plays the role of tonifying the kidney, strengthening the spleen, lowering turbidity, and removing blood stasis.

[0072] In a preferred embodiment of the present invention, the pharmaceutical composition comprises the following raw material components by weight:

[0073] 20-40 parts of Astragalus, for example 20 parts, 30 parts, 40 parts, preferably 30 parts;

[0074] 10-20 parts of Cordyceps sinensis, for example 10 parts, 15 parts, 20 parts, preferably 15 parts;

[0075] 6-15 parts of Taxus chinensis, for example 6 parts, 9 parts, 12 parts, 15 parts, preferably 9 parts;

[0076] 6-12 parts of Panax notoginseng; for example, 6 parts, 9 parts, 12 parts, preferably 9 parts;

[0077] 10-20 parts of wolfberry, for example 10 parts, 15 parts, 20 parts, preferably 15 parts;

[0078] 16-20 parts of cooked polygonatum, for example 16 parts, 18 parts, 20 parts, preferably 18 parts;

[0079] 10-20 parts of Ganoderma lucidum; for example, 10 parts, 15 parts, 20 parts, preferably 15 parts;

[0080] 16-20 parts of Pueraria root; for example, 16 parts, 18 parts, 20 parts, preferably 18 parts;

[0081] Gynostemma pentaphyllum 15-25 parts; for example 15 parts, 20 parts, 25 parts, preferably 20 parts;

[0082] 16-20 parts of Sophora flavescens, for example 16 parts, 18 parts, 20 parts, preferably 18 parts;

[0083] Eucommia ulmoides 10-14 parts; for example, 10 parts, 12 parts, 14 parts, preferably 12 parts;

[0084] 6-12 parts of Curcuma zedoaria, for example 6 parts, 9 parts, 12 parts, preferably 9 parts;

[0085] 20-40 parts of Smilax glabra, for example 20 parts, 30 parts, 40 parts, preferably 30 parts;

[0086] 10-20 parts of cooked rhubarb; for example, 10 parts, 15 parts, 20 parts, preferably 15 parts;

[0087] 10-20 parts of Serissa officinalis, for example 10 parts, 15 parts, 20 parts, preferably 15 parts;

[0088] 10-14 parts of Chuanxiong; for example, 10 parts, 12 parts, 14 parts, preferably 12 parts.

[0089] The second aspect of the present invention provides a method for preparing a pharmaceutical composition for treating chronic kidney disease, comprising: crushing each raw material component of the pharmaceutical composition described in the first aspect of the present invention into raw material powders respectively, sieving them, and then mixing them according to a ratio to provide the pharmaceutical composition.

[0090] In the above preparation method, the raw material components of the pharmaceutical composition except for the cooked yew, cooked polygonatum and cooked rhubarb are raw powder, and the cooked yew, cooked polygonatum and cooked rhubarb are cooked powder.

[0091] The raw powder is used directly from Chinese medicinal materials, which can retain all the ingredients of the medicinal materials and have comprehensive medicinal effects. The cooked powder is processed to enhance the efficacy and reduce the toxicity and irritation of the medicine.

[0092] In one embodiment, the cooked yew is obtained by removing impurities from the yew, rinsing with clean water, spreading it in a steamer, steaming it, and drying it in the sun.

[0093] In a preferred embodiment, the steaming time is 0.5-2 hours, preferably 1 hour, and the steam temperature is 90-130° C., preferably 100-120° C. The steaming can remove the greenness of the leaves of Taxus chinensis.

[0094] In one embodiment, the cooked polygonatum is obtained by removing impurities from the polygonatum, rinsing with clean water, cooling to half dry, spraying with rice wine, moistening it, spreading it in a steamer, steaming it, and drying it.

[0095] In a preferred embodiment, the clean water rinse is a quick clean water rinse. Avoid long-term soaking.

[0096] In a preferred embodiment, the rice wine is evenly sprayed on the polygonatum.

[0097] In a preferred embodiment, the time of soaking is 3-5 hours, preferably 4 hours, so that the wine is completely absorbed by the polygonatum.

[0098] In a preferred embodiment, the steaming time is 3-7 hours, preferably 4-6 hours, and the steam temperature is 90-110° C., preferably 100° C. The steaming makes the polygonatum odoratum dark brown.

[0099] In a preferred embodiment, the drying temperature is ≤60° C., preferably 60° C., so that the water content in the cooked polygonatum is ≤15%.

[0100] In one embodiment, the cooked rhubarb is obtained by removing impurities from the rhubarb, rinsing with clean water, cooling to half dry, spraying with rice wine and then moistening, spreading in a steamer to steam, and drying.

[0101] In a preferred embodiment, the clean water rinse is a quick clean water rinse. Avoid long-term soaking.

[0102] In a preferred embodiment, the rhubarb is sliced ​​when it is cooled and semi-dried. The rhubarb is sliced ​​into thin slices.

[0103] In a preferred embodiment, the rice wine is evenly sprayed on the rhubarb.

[0104] In a preferred embodiment, the time of soaking is 3-7 hours, preferably 4-6 hours, so that the rhubarb can absorb all the wine.

[0105] In a preferred embodiment, the steaming time is 1-4 hours, preferably 2-3 hours, and the steam temperature is 90-110° C., preferably 100-105° C. The steaming process makes the rhubarb dark brown and transparent without white core.

[0106] In a preferred embodiment, the drying is selected from oven drying or shade drying.

[0107] In a preferred embodiment, the drying temperature is ≤60° C., preferably 60° C., so that the water content in the cooked rhubarb is ≤12%.

[0108] In the above preparation method, the mesh size of the sieve is ≥80 mesh, preferably 80 mesh.

[0109] The third aspect of the present invention provides a traditional Chinese medicine preparation, comprising a therapeutically effective amount of the pharmaceutical composition provided by the first aspect of the present invention, and one or more conventional pharmaceutically acceptable excipients.

[0110] Pharmaceutically acceptable excipients include, but are not limited to, pharmaceutically acceptable carriers, diluents, fillers, binders, disintegrants, lubricants, suspending agents, adhesives, sweeteners, flavoring agents, preservatives and other excipients. Therapeutic inert inorganic or organic carriers known to those skilled in the art include, but are not limited to, lactose, corn starch or its derivatives, talc, vegetable oils, waxes, fats, polyol compounds such as polyethylene glycol, water, sucrose, ethanol, glycerol, and the like, various preservatives, lubricants, dispersants, flavoring agents, humectants, antioxidants, sweeteners, colorants, stabilizers, salts, buffers and the like may also be added thereto, and these substances are used to help the stability of the formulation or to help improve the activity or its biological effectiveness as required.

[0111] In the above-mentioned traditional Chinese medicine preparations, the dosage form of the traditional Chinese medicine preparations includes but is not limited to tablets, capsules, pills, syrups, granules, powders, pastes, pellets, suspensions or emulsions.

[0112] The fourth aspect of the present invention provides a traditional Chinese medicine pill, comprising a therapeutically effective amount of the pharmaceutical composition provided by the first aspect of the present invention.

[0113] The therapeutically effective amount in the present invention is calculated based on the total weight of the raw medicinal materials. The specific dosage should also take into account factors such as the route of administration and the patient's health status, which are all within the skills of skilled physicians.

[0114] The fifth aspect of the present invention provides a method for preparing a Chinese medicine pill, comprising: adding the pharmaceutical composition provided in the first aspect of the present invention to auxiliary materials for mixing and pilling, drying, and screening to provide the Chinese medicine pill.

[0115] In the above preparation method, the mass ratio of the pharmaceutical composition to the added excipients is 9-11:1, preferably 10:1.

[0116] In the above preparation method, the auxiliary material is at least one of starch or water.

[0117] In one embodiment, the auxiliary material comprises the following components by mass percentage: 10%-30% starch; 70-90% water.

[0118] In the above preparation method, during the pill making process, the pharmaceutical composition is added with auxiliary materials and mixed and kneaded into a soft material that "can be formed into a ball when held and will fall apart when lightly pressed".

[0119] In the above preparation method, the drying is selected from one of oven drying or shade drying.

[0120] In one embodiment, the drying temperature is ≤ 60° C., preferably 60° C. to avoid the components from being destroyed.

[0121] In the above preparation method, during the screening, the mass of the pills is 7-9 pills / g, preferably 8 pills / g; the diameter of the pills is 4-6 mm / pill, preferably 5 mm / pill.

[0122] In the above preparation method, packaging is performed after screening, and the packaging specifications are 10-50 packages per bag, preferably 30 packages per bag; each package is 1-20g, preferably 10g per package.

[0123] The sixth aspect of the present invention provides the use of the pharmaceutical composition provided in the first aspect of the present invention, the traditional Chinese medicine preparation provided in the third aspect of the present invention, or the traditional Chinese medicine pill provided in the fourth aspect of the present invention in the preparation of a medicament for treating chronic kidney disease.

[0124] In the above use, the chronic kidney disease is chronic kidney disease (CKD).

[0125] In one embodiment, the chronic kidney disease is diabetic kidney disease (DKD) (CKD stage 1-3), chronic renal failure (CKD stage 2-4) or metabolism-related kidney disease.

[0126] Chronic Kidney Disease (CKD) is mainly divided into two categories according to the cause of the disease: primary and secondary. Primary kidney disease is common in IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, etc.; secondary kidney disease is common in diabetic nephropathy, hypertensive nephropathy, obesity-related nephropathy, lupus nephritis, etc. The diagnosis and staging standards of CKD refer to the standards published by KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, including any of the following indicators for more than 3 months to be diagnosed. 1. Meet one or more of the following renal damage: ① albuminuria (AER ≥ 30mg / 24h); ACR ≥ 30mg / g (≥ 3mg / mmol); ② abnormal urine sediment; ③ electrolyte abnormalities and other abnormal tissue pathological abnormalities caused by renal tubular dysfunction; ④ abnormal kidney structure suggested by imaging examination; ⑤ kidney transplant experience. 2. Decreased GFR, GFR < 60 ml / min / 1.73 m 2 .

[0127] CKD can be divided into 5 stages, according to the following criteria:

[0128] CKD stage 1: GFR ≥ 90 mL / min / 1.73 m 2Kidney function is basically normal, but kidney damage has occurred.

[0129] CKD stage 2: GFR 60-89mL / min / 1.73m 2 , mild renal decline, usually without obvious symptoms.

[0130] CKD stage 3: GFR 30-59mL / min / 1.73m 2 , moderate renal function decline, may cause anemia, hypertension and other symptoms.

[0131] CKD stage 4: GFR 15-29mL / min / 1.73m 2 , severe renal function decline, renal replacement therapy needs to be considered according to the condition.

[0132] CKD stage 5 (end-stage renal disease): GFR < 15 mL / min / 1.73 m 2 , requiring dialysis or a kidney transplant to stay alive.

[0133] Treatment and management strategies vary for each of these stages.

[0134] The diabetic kidney disease (DKD) is a chronic kidney disease (CKD) caused by DM, with a complex pathogenesis and clinical features of persistent increased excretion of albuminuria and (or) progressive decrease in glomerular filtration rate (GFR), which eventually develops into end-stage renal disease (ESRD). DKD is the main cause of ESRD. About 30% to 50% of ESRD worldwide is caused by DKD. DKD has become the primary cause of ESRD in middle-aged and elderly people in my country.

[0135] The present invention is mainly suitable for patients with DKD (CKD stage 1-3), chronic renal failure (CKD stage 2-4) or metabolism-related kidney disease.

[0136] The present invention is further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of protection of the present invention.

[0137] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0138] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those generally understood by those skilled in the art.

[0139] The production processes, experimental methods or detection methods involved in the embodiments and comparative examples of the present invention are all conventional methods in the prior art unless otherwise specified, and their names and / or abbreviations are all conventional names in the field and are very clear and unambiguous in the relevant application fields. Those skilled in the art can understand the conventional process steps based on the names and apply the corresponding equipment to implement them according to conventional conditions or the conditions recommended by the manufacturer.

[0140] The various instruments, equipment, raw materials or reagents used in the embodiments of the present invention are not particularly limited in terms of their sources, and are all conventional products that can be purchased through regular commercial channels, or can be prepared according to conventional methods well known to those skilled in the art. Unless otherwise specified, the sources of cells, animals, and drugs involved in the embodiments of the present invention are all commercially available.

[0141] Example 1

[0142] The raw material components of the pharmaceutical composition for treating chronic kidney disease are taken by weight, namely: 30 parts by weight of Astragalus, 15 parts by weight of Cordyceps sinensis, 9 parts by weight of Taxus chinensis, 9 parts by weight of Panax notoginseng, 15 parts by weight of Lycium barbarum, 18 parts by weight of Polygonatum sibiricum, 15 parts by weight of Ganoderma lucidum, 18 parts by weight of Pueraria lobata, 20 parts by weight of Gynostemma pentaphyllum, 18 parts by weight of Sophora flavescens, 12 parts by weight of Eucommia ulmoides, 9 parts by weight of Curcuma zedoaria, 30 parts by weight of Smilax glabra, 15 parts by weight of Rhubarb, 15 parts by weight of Psoralea corylifolia, and 12 parts by weight of Ligusticum chuanxiong, to obtain pharmaceutical composition sample 1#.

[0143] Example 2

[0144] The raw material components of the pharmaceutical composition for treating chronic kidney disease are taken by weight, namely: 20 parts by weight of Astragalus, 20 parts by weight of Cordyceps sinensis, 12 parts by weight of Taxus chinensis, 12 parts by weight of Panax notoginseng, 10 parts by weight of Lycium barbarum, 16 parts by weight of Polygonatum sibiricum, 20 parts by weight of Ganoderma lucidum, 16 parts by weight of Pueraria lobata, 15 parts by weight of Gynostemma pentaphyllum, 20 parts by weight of Sophora flavescens, 10 parts by weight of Eucommia ulmoides, 6 parts by weight of Curcuma zedoaria, 40 parts by weight of Smilax glabra, 10 parts by weight of Rhubarb, 10 parts by weight of Psoralea corylifolia, and 14 parts by weight of Ligusticum chuanxiong, to obtain pharmaceutical composition sample 2#.

[0145] Example 3

[0146] The raw material components of the pharmaceutical composition for treating chronic kidney disease are taken by weight, namely: 40 parts by weight of Astragalus, 10 parts by weight of Cordyceps sinensis, 6 parts by weight of Taxus chinensis, 6 parts by weight of Panax notoginseng, 20 parts by weight of Lycium barbarum, 20 parts by weight of Polygonatum sibiricum, 10 parts by weight of Ganoderma lucidum, 20 parts by weight of Pueraria lobata, 25 parts by weight of Gynostemma pentaphyllum, 16 parts by weight of Sophora flavescens, 14 parts by weight of Eucommia ulmoides, 12 parts by weight of Curcuma zedoaria, 20 parts by weight of Smilax glabra, 20 parts by weight of Rhubarb, 20 parts by weight of Psoralea corylifolia, and 10 parts by weight of Ligusticum chuanxiong, to obtain pharmaceutical composition sample 3#.

[0147] Example 4

[0148] The above-mentioned drug composition sample 1# is added to the auxiliary materials and mixed to make pills, and the mass ratio of the drug composition to the auxiliary materials is 10:1. The auxiliary materials include the following components by mass percentage: 20% starch; 80% water. Then it is dried at 60℃, and the mass of the pills obtained by screening is 8 pills / gram; the diameter of the pills is 5mm / pill. After screening, it needs to be packaged, and the packaging specifications are 30 packages in each bag; each package is 10g. The traditional Chinese medicine pill sample 1* is obtained.

[0149] Example 5

[0150] The above-mentioned drug composition sample 2# is added to the auxiliary materials and mixed to make pills, and the mass ratio of the drug composition to the auxiliary materials is 11:1. The auxiliary materials include the following components by mass percentage: 30% starch; 70% water. Then it is dried in the shade at room temperature, and the mass of the pills obtained by screening is 7 pills / gram; the diameter of the pills is 6mm / pill. After screening, it needs to be packaged, and the packaging specifications are 40 packages in each bag; each package is 5g. The traditional Chinese medicine pill sample 2* is obtained.

[0151] Example 6

[0152] The above-mentioned drug composition sample 3# was added to the auxiliary materials and mixed to make pills, and the mass ratio of the drug composition to the auxiliary materials was 9:1. The auxiliary materials, by mass percentage, included the following components: 10% starch; 90% water. Then, the pills were dried at 50°C and screened to obtain a mass of 9 pills / gram; the diameter of the pills was 4 mm / pill. After screening, the pills were packaged, and the packaging specifications were 20 packages per bag; each package was 15g. The Chinese medicine pill sample 3* was obtained.

[0153] Test Example 1

[0154] 1. Case selection

[0155] 1.1 Diagnostic criteria

[0156] (1) Western medicine diagnostic criteria: The diagnostic criteria for diabetic kidney disease refer to the "Chinese Guidelines for Clinical Diagnosis and Treatment of Diabetic Kidney Disease" issued by the Expert Group of the Nephrology Branch of the Chinese Medical Association in 2021. The patient has a clear history of diabetes and a certain causal relationship with changes in urine protein and renal function, and kidney disease caused by other reasons has been excluded, and meets one of the following conditions:

[0157] ① Random urine albumin-to-creatinine ratio (UACR) ≥ 30 mg / g or urine albumin excretion rate (UAER) ≥ 30 mg / 24 h, and UACR or UAER is repeated within 3 to 6 months, and 2 out of 3 times reaches or exceeds the critical value; other interfering factors such as infection, tumor, autoimmune disease, etc. are excluded.

[0158] ②Estimated glomerular filtration rate (eGFR) <60 ml / min / 1.73 m 2 More than 3 months.

[0159] ③ Renal biopsy is consistent with DKD pathological changes. The Western medical diagnostic criteria for chronic kidney disease refer to the standards published by KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.

[0160] (2) TCM syndrome differentiation standards: The syndrome differentiation of kidney deficiency, turbidity and blood stasis refers to the relevant standards in the "TCM Clinical Diagnosis and Treatment Terminology Part 2: Syndromes" (revised version) issued by the State Administration of Traditional Chinese Medicine and the National Health Commission in November 2020 and the "Diagnosis, Syndrome Differentiation and Efficacy Evaluation of Chronic Renal Failure (Trial Program)" formulated by the Nephrology Branch of the Chinese Association of Traditional Chinese Medicine in 2006.

[0161] 1.2 Inclusion criteria

[0162] The patient meets the above-mentioned Western medical diagnostic criteria and TCM syndrome differentiation criteria; hypertension, severe infection, water electrolyte and acid-base imbalance are effectively controlled, and blood K+ is within the normal range; the lead-in period is 2 weeks, and the patient must test GFR at the beginning and end of the lead-in period, and the results of both tests meet the standard (GFR ≥ 30 mL / min / 1.73 m 2 ). Aged 18-70 years old, regardless of gender; signed informed consent.

[0163] 1.3 Exclusion criteria

[0164] Patients with serious primary diseases of the heart, brain, liver and hematopoietic system; those who have undergone kidney transplantation; mental patients; patients with acute renal failure; pregnant or lactating women; those who are known to be allergic to the drugs used; those who are participating in clinical trials of other drugs or have participated in other clinical trials within 3 months.

[0165] 1.4 Elimination criteria

[0166] Those who have poor compliance, cannot cooperate with dietary control, or do not take medication as prescribed, which affects the judgment of efficacy.

[0167] 2. General Information

[0168] The included cases were from the Department of Traditional Chinese Medicine of Shanghai Pudong New Area People's Hospital (60 cases), Chuansha Community Health Service Center (30 cases) and Tangzhen Community Health Service Center (30 cases), all of which met the diagnosis of DKD (CKD stage 1-3) and were clearly diagnosed as kidney deficiency, turbidity and blood stasis by more than two attending physicians of traditional Chinese medicine. According to the clinical visit order of the patients, the statisticians generated a stratified random number table using SAS software and randomly divided the patients into a treatment group and a control group, with 60 cases in each group.

[0169] 3. Treatment methods

[0170] 3.1 Control group

[0171] The treatment of the control group mainly includes diet and nutrition, control of blood pressure, blood lipids, etc. ① Diet and nutrition: refer to the "Expert Consensus on Protein Nutrition Treatment of Chronic Kidney Disease", protein intake is 0.8-1.0g·kg -1 ·d -1 , of which high biological value protein> 50%. While on a low-protein diet, calorie intake should be maintained at 30-35 kcal kg -1 ·d -1. A special nutritionist was hired to provide individualized guidance and make reference meals according to the specific weight, height and renal function of each enrolled patient. ② Control blood pressure: For patients with elevated blood pressure, refer to the JNCVII and K / DOQI recommended standards, and according to the urine protein quantification, reduce blood pressure to below 130 / 80mmHg and 125 / 75mmHg respectively. CCB preparations are the first choice for antihypertensive drugs. If blood pressure cannot be controlled at the target, antihypertensive drugs such as central or receptor antagonists can be added. ACEI and ARB antihypertensive drugs other than those specified in this plan cannot be used. ③ Control blood lipids: For patients with elevated blood lipids, refer to the 1997 recommendations for blood lipid prevention and treatment in my country and the "National Cholesterol Education Program Third Report (NCEPATPIII)" standards published in May 2001 in the United States, so that TCH <5.72mmol / L, LDL <3.64mmol / L, TG <2.26mmol / L. Lipid-regulating drugs can be selected from atorvastatin 20mg / d, and the course of treatment is 3 months.

[0172] 3.2 Treatment groups

[0173] On the basis of the treatment of the control group, the Chinese medicine pill sample 1* prepared in Example 4 was added. Dosage: Swallow with warm water, 3 times a day, 1 pack each time, 3 months as a course of treatment.

[0174] 4. Observation items and methods

[0175] 4.1 Clinical efficacy

[0176] Refer to the relevant standards in the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" and "Diagnosis, Syndrome Differentiation and Efficacy Evaluation of Chronic Renal Failure" to judge the clinical efficacy. ① Significant effect: clinical symptom score reduction ≥ 60%, endogenous creatinine clearance or glomerular filtration rate increase ≥ 30%, blood creatinine decrease ≥ 30%; ② Effective: clinical symptom score reduction ≥ 30%, endogenous creatinine clearance or glomerular filtration rate increase ≥ 15%, blood creatinine decrease ≥ 15%; ③ Stable: clinical symptoms improved, symptom score reduction < 30%, endogenous creatinine clearance or glomerular filtration rate did not decrease or increase < 15%, blood creatinine did not increase or decreased < 15%; ④ Ineffective: clinical symptoms did not improve or worsened, endogenous creatinine clearance or glomerular filtration rate decreased, blood creatinine increased. All of the above are required for the first item, and one of the second and third items can be determined.

[0177] 4.2 TCM Syndrome Score

[0178] The integration method was used to observe the improvement of TCM symptoms before and after treatment, and each symptom was scored as 0, 2, 4, and 6 points according to none, mild, moderate, and severe, respectively.

[0179] 4.3 Laboratory indicators

[0180] Before and after treatment, all patients were tested for 24h urine protein quantification (24h UTP), 24h urine protein excretion rate (24hUAER), urine microalbumin / urine creatinine (UACR), and urine-β 2 -Microglobulin (U-β 2 -MG), hemoglobin (Hb), red blood cell (RBC), serum albumin (Alb), D-dimer (DD), fibrin degradation product (FDP), serum cystatin (Cys-C), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), total cholesterol (TCH), triglyceride (TG), fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG) levels, and the estimated glomerular filtration rate (eGFR) was compared between the two groups.

[0181] 4.4 Follow-up

[0182] During the 3-month treatment, the incidence of ESRD and CKD grade of the two groups were recorded. After the 3-month treatment, the two groups were followed up for 24 months to compare the incidence of renal composite risk and UACR changes. Renal composite risk refers to the observation of ESKD, renal failure risk equation (KFRT) or eGFR <15mL / min / 1.73m 2 The following events were classified as renal death: ① the patient died; ② renal replacement therapy was not started despite clinical indications; ③ there were no other possible causes of death.

[0183] 5. Statistical methods

[0184] The experimental data were statistically analyzed using SPSS15.0 software package. The measurement data were expressed as xˉ±s. The paired t test was used for intra-group comparison before and after treatment, and the independent sample t test was used for comparison between the two groups after treatment. The Ridit analysis was used for rank counting data, and the chi-square test was used for non-rank counting data. P<0.05 was considered statistically significant.

[0185] 6. Results

[0186] 6.1 Baseline information

[0187] There was no significant difference in gender composition, age, disease course, Scr, eGFR, 24h UTP levels between the two groups (P>0.05), and the two groups were comparable. See Table 1.

[0188] Table 1 Comparison of baseline data between the two groups of patients

[0189]

[0190] 6.2 Clinical efficacy

[0191] The total clinical effective rates of the treatment group and the control group were 91.67% and 78.33%, respectively. The clinical efficacy of the two groups was compared by Ridit analysis, and the difference was statistically significant (P<0.01). The efficacy of the treatment group was better than that of the control group. See Table 2 for details.

[0192] Table 2 Comparison of clinical efficacy between the two groups of patients [cases (%)]

[0193]

[0194] Note: Compared with the control group, **P<0.01.

[0195] 6.3 TCM Syndrome Score

[0196] Before treatment, there was no significant difference in the TCM syndrome scores between the two groups (P>0.05). After treatment, the TCM syndrome scores of the treatment group were reduced (P<0.05, P<0.01), and the scores of dry stool and throat, fatigue, nausea and vomiting, greasy tongue coating, cyanosis of lips and nails, and dark purple tongue in the treatment group were lower than those in the control group (P<0.05, P<0.01). See Table 3 for details.

[0197] Table 3 Comparison of TCM syndrome scores between the two groups of patients ( point)

[0198]

[0199] Note: Compared with the group before treatment, *P<0.05, **P<0.01; compared with the control group after treatment, #P<0.05, ##P<0.01.

[0200] 6.4 Residual renal function

[0201] Before treatment, there was no significant difference in the levels of various renal function indicators between the two groups (P>0.05). After treatment, the levels of Scr, BUN, UA, Cys-C, and eGFR in the two groups were improved compared with those before treatment (P<0.05, P<0.01), and the improvement of Scr, BUN, UA, Cys-C, and eGFR in the treatment group was better than that in the control group (P<0.05, P<0.01). See Table 4 for details.

[0202] Table 4 Comparison of renal function index levels between the two groups of patients

[0203]

[0204] Note: Compared with the group before treatment, *P<0.05, **P<0.01; compared with the control group after treatment, #P<0.05.

[0205] 6.5 Monitoring of FPG and 2hPG during 12 weeks of treatment

[0206] After the fourth week of treatment, the FPG and 2hPG levels in the treatment group gradually stabilized and gradually decreased with the extension of treatment time, with statistically significant differences compared with the control group (P<0.05, P<0.01). See Table 5 for details.

[0207] Table 5 Comparison of FPG and 2hPG monitoring between the two groups of patients at 12 weeks

[0208]

[0209] Note: Compared with the control group, #P<0.05, ##P<0.01.

[0210] 6.6TCH, TG levels

[0211] Before treatment, there was no significant difference in TCH and TG levels between the two groups (P>0.05). After treatment, the TCH and TG levels of the two groups decreased compared with those before treatment (P<0.05, P<0.01), and the TCH and TG levels of the treatment group were lower than those of the control group (P<0.05, P<0.01). See Table 6 for details.

[0212] Table 6 Comparison of TCH and TG levels between the two groups of patients

[0213]

[0214] Note: Compared with the group before treatment, *P<0.05, **P<0.01; compared with the control group after treatment, #P<0.05, ##P<0.01.

[0215] 6.7UACR, 24h UTP and U-β2-MG levels

[0216] After treatment, UACR, 24h UTP and U-β 2 -MG level was significantly lower than that before treatment (P<0.01), and 24h UTP level of the control group was also lower than that before treatment (P<0.05). 2 The difference of -MG level between the control group and the control group was statistically significant (P<0.05, P<0.01).

[0217] Table 7 UACR, 24h UTP and U-β in the two groups of patients 2 -MG level comparison

[0218]

[0219] Note: Compared with the group before treatment, *P<0.05, **P<0.01; compared with the control group after treatment, #P<0.05, ##P<0.01.

[0220] Comparison of 6.8Hb, RBC and Alb levels

[0221] After treatment, Hb, RBC, and Alb in the treatment group were significantly higher than those before treatment, with statistically significant differences (P<0.05, P<0.01), while there was no significant difference in the control group compared with before treatment; and after treatment, Hb, RBC, and Alb in the treatment group were statistically significant or significantly different from those in the control group (P<0.05, P<0.01). See Table 8 for details.

[0222] Table 8 Comparison of Hb, RBC and Alb levels between the two groups of patients

[0223]

[0224] Note: Compared with the group before treatment, *P<0.05, **P<0.01; compared with the control group after treatment, #P<0.05, ##P<0.01.

[0225] 6.9 Comparison of DD and FDP levels

[0226] After treatment, the DD and FDP levels of the two groups of patients decreased compared with those before treatment (P<0.01), and the DD and FDP levels of the treatment group were lower than those of the control group (P<0.05). See Table 9 for details.

[0227] Table 9 Comparison of DD and FDP levels between the two groups of patients

[0228]

[0229] 6.10 Follow-up

[0230] 6.10.1 During treatment

[0231] 120 patients were followed up once a month for a total of 3 months. During the follow-up, 2 patients in the control group were lost to follow-up (for unknown reasons), and all patients in the treatment group completed follow-up. In the control group, 5 patients progressed to CKD stage 4, and 3 patients entered CKD stage 5; in the treatment group, 3 patients progressed to CKD stage 4, and 0 patients entered CKD stage 5. All 3 ESRD patients in the control group were transferred to blood purification or peritoneal dialysis treatment, and the ESRD incidence was 5.17%. The comparison of the ESRD incidence between the two groups showed statistically significant difference (P<0.01). See Table 10 for details.

[0232] Table 10 Comparison of CKD progression and ESRD incidence between the two groups during the 3-month follow-up

[0233]

[0234] Note: Compared with the control group, *P<0.05, **P<0.01.

[0235] 6.10.2 Risk of renal composite endpoints after 24-month follow-up

[0236] The incidence of renal composite endpoints in the treatment group was 3.33% at 9 months of follow-up, while that in the control group was 7.14%; at 12 months of follow-up, the cumulative incidence of renal composite endpoints in the treatment group was 3.39%, while that in the control group was 7.41%; at 24 months of follow-up, the cumulative incidence of renal composite endpoints in the treatment group was 6.9%, while that in the control group was 9.62%. The relative risk reduction rate (RRR) of the treatment group was 39.42%, with a 95% CI confidence interval of (0.78-0.93), P<0.01. See Table 11 for details. Figure 1 .

[0237] Table 11 Comparison of the risk rate of renal composite endpoints between the two groups of patients after 24 months of follow-up (%)

[0238]

[0239] Note: Compared with the control group, ##P<0.01.

[0240] 6.10.3 UACR at 24-month follow-up

[0241] During the 24-month follow-up, the UACR in the treatment group was significantly reduced by 17.21% compared with the control group, and the effect was sustained, with significant differences after statistical analysis (P<0.01). See Table 12, Figure 2 .

[0242] Table 12 Comparison of UACR (mg / g) between the two groups of patients at 24 months of follow-up

[0243]

[0244] Note: Compared with the control group, ##P<0.01.

[0245] 7. Conclusion

[0246] The experimental results of the test examples show that taking the Chinese medicine pills in the present invention combined with conventional treatment has a significant improvement effect on the clinical syndrome of DKD patients with kidney deficiency, turbidity and stasis syndrome. The prescription can reduce the patient's 24hUAER, UACR, urine-β 2-microglobulin, improves the patient's plasma albumin and hemoglobin levels, relieves the patient's edema, anemia and malnutrition, improves the triglycerides of CKD patients and reduces serum cholesterol levels. In terms of protecting the patient's residual renal function, the patients taking this prescription had significantly improved levels of blood creatinine, urea nitrogen, and blood uric acid, and increased eGFR, with an overall effective rate of 91.67%. In the subsequent 24-month follow-up, this prescription was able to reduce the cumulative rate of renal composite risk by 39.42%, significantly reduce UACR, and the effect was sustained, which was significantly better than the control group. Studies have shown that urine beta 2 Microglobulin and serum cystatin levels have high sensitivity and specificity for diagnosing early renal damage in patients, and have important guiding significance for the early diagnosis, early treatment and control of DKD (stages 1-3) patients. The Chinese medicine pills of the present invention can reduce serum cystatin levels and urine β 2 Microglobulin, indicating that this prescription plays a certain role in protecting renal function and alleviating kidney damage. Studies have shown that the DD and FDP levels of DKD patients are significantly increased. If not treated in time, the occurrence of end-stage renal failure will be accelerated, and serious complications such as thrombosis and thromboembolism are also likely to endanger life. Therefore, early diagnosis and treatment of DKD coagulation and fibrinolytic system imbalance will significantly improve the patient's survival time and quality of life. Traditional Chinese medicine believes that the imbalance of the coagulation and fibrinolytic system is a state of blood stasis. DKD has many syndromes, which is related to the patient's continuous state of blood stasis. The Chinese medicine pills in the present invention can significantly reduce the levels of DD and FDP, improve renal circulation, and then play a role in protecting the kidneys and delaying the progress of chronic renal failure.

[0247] The above is only a preferred embodiment of the present invention, and is not any formal or substantial limitation of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any technician familiar with this profession, without departing from the spirit and scope of the present invention, can make some changes, modifications and evolutions of the technical content disclosed above, which are equivalent embodiments of the present invention; at the same time, any changes, modifications and evolutions of any equivalent changes made to the above embodiments based on the essential technology of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition, comprising the following raw material components by weight: 10-50 parts by weight of Astragalus; 5-30 parts by weight of Cordyceps sinensis; 3-15 parts by weight of Taxus chinensis; 3-15 parts by weight of Panax notoginseng; 5-30 parts by weight of wolfberry; 10-25 parts by weight of cooked polygonatum; 5-30 parts by weight of Ganoderma lucidum; 10-25 parts by weight of Pueraria root; Gynostemma pentaphyllum 10-30 parts by weight; Sophora flavescens 10-25 parts by weight; Eucommia ulmoides 5-20 parts by weight; 3-15 parts by weight of Curcuma zedoaria; 10-50 parts by weight of Rhizoma Smilacis Glabrae; 5-30 parts by weight of cooked rhubarb; 5-30 parts by weight of Serissa rutinae; 5-20 parts by weight of Ligusticum chuanxiong.

2. A method for preparing a pharmaceutical composition, comprising: The raw material components of the pharmaceutical composition according to claim 1 are crushed into raw material powders respectively, sieved, and then mixed according to a proportion to provide the pharmaceutical composition.

3. The method for preparing the pharmaceutical composition according to claim 2, characterized in that: The mesh number of the sieve is ≥80 meshes.

4. A Chinese medicine preparation comprising a therapeutically effective amount of the pharmaceutical composition according to claim 1, and one or more conventional pharmaceutically acceptable excipients.

5. A Chinese medicine pill comprising a therapeutically effective amount of the pharmaceutical composition according to claim 1.

6. A method for preparing a Chinese medicine pill, comprising: The pharmaceutical composition according to claim 1 is added with auxiliary materials to mix and make pills, dried and screened to provide the traditional Chinese medicine pills.

7. The method for preparing the Chinese medicine pill according to claim 6, characterized in that: Includes any one or more of the following conditions: 1) The mass ratio of the pharmaceutical composition to the excipients added is 9-11:1; 2) The auxiliary material is at least one of starch or water; 3) The drying is selected from one of oven drying or shade drying; 4) In the screening, the mass of the pills is 7-9 pills / g; the diameter of the pills is 4-6 mm / pill; 5) After the screening, the product is packaged, with the packaging specifications being 10-50 packages per bag and 1-20g per package.

8. The method for preparing the Chinese medicine pill according to claim 7, characterized in that: Also includes any one or more of the following conditions: 21) In item 2), the auxiliary materials include the following components by mass percentage: starch 10%-30%; water 70-90%. 31) In item 3), the drying temperature is ≤ 60°C.

9. Use of the pharmaceutical composition according to claim 1, the traditional Chinese medicine preparation according to claim 4, or the traditional Chinese medicine pill according to claim 5 in the preparation of a medicament for treating chronic kidney disease.

10. The use according to claim 9, characterized in that The chronic kidney disease is chronic kidney disease; preferably, the chronic kidney disease is diabetic kidney disease in CKD stage 1-3, chronic renal failure in CKD stage 2-4, or metabolism-related kidney disease.

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