Application of traditional Chinese medicine composition in preparation of medicine for treating CKD

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating CKD, and relates to the technical field of CKD treatment. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-7 parts of leech, 5-7 parts of stiff silkworm and 8.5-11.5 parts of rheum officinale. 45-55 parts of radix astragali seu hedysari; according to the traditional Chinese medicine composition, for patients in the CKD3 stage and the CKD4 stage, the Scr and UA levels of the patients are remarkably reduced, GRF decline is delayed, and abnormal bone metabolism is corrected. The traditional Chinese medicine preparation is simpler in process and simple to operate. The renal failure pill can be clinically used for 10 years in Wuhan United Hospital, has small toxic and side effects and definite curative effect, and is widely accepted by patients. Clinical research shows that the renal failure pill can obviously reduce serum creatinine and urea nitrogen levels of CKD and delay the progress of CKD.

Description

Technical Field

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

[0002] Chronic kidney disease (CKD) is a disease of chronic kidney structure and function disorders (history of kidney damage for more than 3 months) caused by various reasons, and the terminal stage is uremia. CKD has a high incidence, a long course of disease, a complex pathogenesis, a poor prognosis, and there is currently no specific treatment. Traditional nutritional therapy is mainly used in the clinic to treat complications and comorbidities. The terminal stage is blood purification therapy and kidney transplantation. However, nutritional therapy has a long cycle, slow treatment effect, and can only delay the progression of CKD within a limited range; alternative therapies such as hemodialysis and peritoneal dialysis have large side effects and high costs; kidney transplantation has problems such as a shortage of kidney sources and high surgical costs, rejection reactions after surgery, and the use of a large number of immunosuppressants that make patients immune to low problems, which brings serious economic and social burdens to patients' families and society.

[0003] According to the theory of traditional Chinese medicine, CKD is a syndrome of deficiency of the body and excess of pathogens. Deficiency of the body is mainly caused by the deficiency of qi, blood, yin and yang, and the deficiency of spleen and kidney. Excess pathogens include dampness, blood stasis, water vapor, and external pathogens, which are important factors in the occurrence and development of CKD. Therefore, accurately grasping the main causes of CKD and using a combination of treatment methods of strengthening the body and eliminating pathogens is the key to treating the disease. Strengthening the body means adjusting the balance of qi, blood, yin and yang in the body, restoring the functions of the internal organs, protecting kidney tissue, and improving the body's disease resistance. Strengthening the body and curing the root cause is mainly based on strengthening the kidney, and is often combined with methods such as strengthening the spleen and nourishing the liver. Specifically, there are methods such as strengthening the spleen and nourishing the kidney, nourishing the kidney and nourishing the liver, nourishing qi and nourishing yin (blood), and replenishing yin and yang. In terms of medication, the principles of replenishing without stagnation, warming without dryness, and nourishing without greasy should be mastered. Expelling pathogens means eliminating external pathogens and water vapor, blood stasis, and turbidity in the body. Commonly used methods of eliminating pathogens include promoting water and removing dampness, clearing heat and detoxifying, clearing the bowels and relieving turbidity, and promoting blood circulation and removing blood stasis. However, current traditional Chinese medicines have little effect in treating CKD.

[0004] Therefore, actively searching for traditional Chinese medicine that can effectively alleviate and delay CKD is of great significance for prolonging non-dialysis time, reducing mortality, and improving patients' quality of life. Summary of the invention

[0005] The invention discloses an application of a traditional Chinese medicine composition in preparing a drug for treating CKD. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-7 parts of leech, 5-7 parts of silkworm, 8.5-11.5 parts of rhubarb, and 45-55 parts of astragalus. The traditional Chinese medicine composition can significantly reduce the Scr and UA levels of patients in CKD stage 3 and CKD stage 4, delay the decline of GRF, and correct the abnormal bone metabolism.

[0006] Preferably, the Chinese medicine composition comprises the following raw materials in optimal weight proportions: 50 parts of astragalus, 10 parts of rhubarb, 6 parts of leech and 6 parts of bombyx batryticatus.

[0007] A traditional Chinese medicine preparation for treating CKD, comprising the traditional Chinese medicine composition.

[0008] The preparation method of the above-mentioned Chinese medicine preparation is as follows:

[0009] 1) Grind 45-55 parts of Astragalus and 2.5-3.5 parts of Rhubarb through an 80-mesh sieve and set aside;

[0010] 2) Add 200 mL of water to 5-7 parts of leeches and 5-7 parts of silkworms and boil for 45-60 minutes, filter and take the supernatant; add the remaining 6-8 parts of rhubarb to the residue and add 200 mL of water and boil for 45-60 minutes, filter and take the supernatant, combine the filtrates and concentrate to a density of 1.12-1.15;

[0011] 3) Add astragalus powder and rhubarb powder, pass through a 10-mesh sieve, and granulate. Then, the pellets are molded, formed, covered, dried, selected, quality inspected, and packaged.

[0012] The prescription composition of the above-mentioned Chinese medicine combination and Chinese medicine preparation is based on summarizing the advantages of traditional Chinese medicine in treating CKD, combining the many years of clinical treatment experience and practice of professors of Chinese medicine and nephrology, starting from the early, middle and late stage symptoms of CKD, and adopting the method of strengthening the body and eliminating evil, to derive the Chinese medicine compound preparation for treating CKD. The pills made are called Shenshuai Pills.

[0013] The present invention has only four Chinese medicinal materials in the prescription composition, namely, astragalus, rhubarb, silkworm and leech. Among them, astragalus is the main drug, and astragalus belongs to the lung and spleen meridians. It is a Chinese medicine with the function of invigorating qi and protecting the kidney, and has the functions of invigorating qi and strengthening the exterior, promoting diuresis and detoxification, expelling pus, and astringing sores and promoting tissue regeneration. Rhubarb has always been known for attacking stagnation, clearing damp heat, purging fire, cooling blood, removing blood stasis and detoxifying. These two flavors, one rising and one falling, are closely linked to the pathogenesis of many edema diseases, such as the ghost gate (sweat pore) not opening and the clean house not being clean due to the failure of clear yang to rise and turbid yin to fall.

[0014] However, in addition to these two methods, the treatment of edema should also "remove the old and the stagnant", that is, to remove blood stasis and phlegm, so the adjuvant leech is selected to promote blood circulation and remove blood stasis. Leech is a blood-activating and blood-stasis-removing drug. Modern research shows that hirudin has anti-coagulation and anti-thrombosis, increases the blood flow of the kidneys, and improves renal function. The main function of leech is to break blood circulation and activate blood stasis, and disperse nodules. At the same time, rhubarb can also promote blood circulation and remove blood stasis, and the adjuvant silkworm can remove phlegm, search for wind and dredge the meridians. Leech and silkworm are both insect drugs, and they have strong attack and expel evil. Take silkworm and rhubarb to take the prescription of Shengjiang San in "Cold and Warm Treatise" to take the effect of raising the clear and lowering the turbid. The four medicines are used together to benefit the qi and strengthen the body, raise the clear and lower the turbid, promote blood circulation and remove phlegm, and promote diuresis, which is beneficial to the symptoms of qi deficiency, blood stasis, phlegm and water retention seen in many kidney diseases. In Shenshuai Pills, astragalus is used to strengthen the body, while rhubarb, leech and silkworm are used to eliminate pathogenic factors. The combination of strengthening the body and eliminating pathogenic factors is used to improve kidney function.

[0015] Compared with the traditional prescription for treating kidney disease, which consists of more than a dozen herbs, the prescription of Shenshuai Pills produced by Wuhan Union Hospital mainly includes four Chinese herbs: rhubarb, astragalus, leech and silkworm. Currently, there is no production and supply of this variety in the domestic market, and the preparation process is simpler and the operation is simpler. Shenshuai Pills have been used clinically in Wuhan Union Hospital for 10 years. They have little toxicity and side effects, definite efficacy, and are more easily accepted by patients. Clinical studies have shown that Shenshuai Pills can significantly reduce the levels of blood creatinine and urea nitrogen in CKD patients and delay the progression of CKD. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings in the following description are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative efforts.

[0017] Figure 1 The figure is a flow chart of a preparation method of Shenshuai Pills. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] 1. Prescription composition and source:

[0020] Prescription composition 1: Astragalus 50g, Rhubarb 10g (7g extracted + 3g powdered), Leech 6g, Bombyx batryticatus 6g;

[0021] Prescription composition 2: Astragalus 45g, Rhubarb 8.5g (6g extract + 2.5g), Leech 5g, Bombyx batryticatus 5g;

[0022] Prescription composition 3: Astragalus 55g, Rhubarb 11.5g (8g extract + 3.5g), Leech 7g, Bombyx batryticatus 7g.

[0023] Source of prescription: The prescription of Shenshuai Wan was developed by experts from the Department of Traditional Chinese Medicine and Nephrology of Wuhan Union Hospital after long-term clinical practice. It was continuously optimized in the process of clinical use, and the composition and preparation method of the prescription were determined by combining the principles of syndrome differentiation and disease differentiation. The prescription of Shenshuai Wan consists of four Chinese medicines, namely, Astragalus, Rhubarb, Leech and Bombyx Batryticatus. Among them, the monarch medicine Astragalus can invigorate qi and promote diuresis, and its nature is mainly ascending, which can open the ghost gate; the minister medicine Rhubarb can clear diarrhea and turbidity, and its nature is mainly descending, which can clean the palace. These two flavors, one ascending and one descending, are closely linked to the pathogenesis of many edema diseases caused by the failure of clear yang to rise and turbid yin to fall, and the ghost gate (sweat pores) not opening and the clean palace not being clean. However, in addition to these two methods, the treatment of edema should also "remove the old and the stagnant", that is, to remove blood stasis and phlegm, so the adjuvant leech is selected to promote blood circulation and remove blood stasis. At the same time, Rhubarb can promote blood circulation and remove blood stasis, and the adjuvant Bombyx Batryticatus can remove phlegm, search for wind and dredge the meridians. Leeches and silkworms are both insect medicines with strong attack and expelling power. The four medicines are used together to benefit qi and strengthen the body, raise the clear and lower the turbid, promote blood circulation, resolve phlegm and promote diuresis, which is beneficial to the symptoms of qi deficiency, blood stasis, phlegm and water retention seen in various kidney diseases.

[0024] Shenshuai Pills can replenish Qi and strengthen the body, raise the clear and lower the turbid, activate blood circulation, resolve phlegm and promote diuresis. It is used for edema caused by Qi deficiency, blood stasis and phlegm stagnation, with symptoms of edema, fatigue, soreness of waist and knees, dark complexion, dark tongue, greasy coating and deep and sluggish pulse. It can be used for various nephritis, proteinuria and renal insufficiency with the above symptoms. It has significant clinical effects.

[0025] 2. Preparation of Shenshuai Pills

[0026] like Figure 1 As shown in the flow chart: Astragalus and rhubarb for powder making are crushed and passed through an 80-mesh sieve for use. Leech and silkworm are boiled with 200 mL of water for 45-60 minutes, filtered, and the supernatant is taken; rhubarb for extraction is added to the filter residue and then boiled with 200 mL of water for 45-60 minutes, filtered, the supernatant is taken, the filtrate is combined, and concentrated to a certain volume (detection density 1.12-1.15). Then astragalus powder and rhubarb powder are added, passed through a 10-mesh sieve, and granulated. After demoulding, forming, covering, drying, pill selection, quality inspection, and packaging, a bottle of 50g of finished product is obtained.

[0027] 3. Clinical trials

[0028] This trial was a retrospective study, and patients who visited the Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2015 were selected. According to the screening criteria, 370 patients were actually enrolled, and the median observation time was 6 months.

[0029] Case enrollment

[0030] Patients who visited the Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2015 were selected and screened strictly according to the diagnostic criteria, inclusion criteria, and exclusion criteria to ensure that there was no significant difference in the amount of data between the groups, and there was no difference in baseline age, gender, disease course, hemoglobin (Hb), serum creatinine (Scr), serum uric acid (UA), estimated glomerular filtration rate (eGFR), urine protein, urine occult blood, and calcium-phosphorus product ([Ca]*[P]) between the groups. The difference between the two groups was statistically significant (all P>0.05), so the baseline data of patients in the same disease stage (CKD3 or CKD4) before medication were comparable. Finally, 370 eligible cases were collected, sorted and retrospectively analyzed. There were 183 patients in CKD3 and 187 patients in CKD4. According to the different medications, they were divided into the following groups (Table 1): the control group (N) who did not take Shenshuai Pills or aldehyde-encapsulated starch, the Shenshuai Pills group (S) and the aldehyde-encapsulated starch group (B).

[0031] Table 1 Experimental grouping

[0032]

[0033] Note: N refers to the control group patients who did not take Shenshuai Pills or aldehyde-encapsulated starch, S refers to the patients who took Shenshuai Pills, and B refers to the patients who took aldehyde-encapsulated starch.

[0034] Effectiveness Analysis

[0035] The changes of UA, Scr, eGFR, [Ca]*[P] and other indicators in patients with CKD stage 3 and CKD stage 4 in the S group (S3, S4) were observed before and after taking Shenshuai Pills for 6 months. The results showed (see Table 2): the UA levels of patients in the S3 and S4 groups were significantly lower than those before taking the medicine for 6 months, and the difference was statistically significant (all P<0.05); the Scr, eGFR and [Ca]×[P] of patients in the S3 group did not change significantly after taking the medicine for 6 months compared with those before 6 months, and the difference was not statistically significant (P>0.05), indicating that Shenshuai Pills can effectively delay the progression of CKD; the Scr, eGFR and [Ca]×[P] of patients in the S4 group increased after taking the medicine for 6 months compared with those before 6 months, and the difference was statistically significant (P<0.05).

[0036]

[0037] Table 2 Comparison of various indicators between CKD stage 3 and CKD stage 4 patients before and after using Shenshuai Pills

[0038] Note: S(a) is the data of CKD patients after using Shenshuai Pills, and S(b) is the data of CKD patients before using Shenshuai Pills. *P<0.05

[0039] To observe the changes of various indicators in patients with CKD stage 3 and CKD stage 4 after using Shenshuai Pills or aldehyde-encapsulated starch for 6 months.

[0040] Table 3 Comparison of various indicators between CKD stage 3 and CKD stage 4 patients after medication

[0041]

[0042] Note: N is the control group of patients who did not take Shenshuai Pills or Baodeoxy starch, S is the patients who took Shenshuai Pills, and B is the patients who took Baodeoxy starch. Compared with Group S or Group B, *P<0.05; compared with Group B, #P<0.05.

[0043] The results show:

[0044] 1) In patients with CKD stage 3 and CKD stage 4, the UA level in group S was significantly lower than that in group N, with a significant statistical difference (P<0.05), while the UA level in group B was not different from that in group N, indicating that Shenshuai Pills has a significant effect in reducing uric acid;

[0045] 2) The Scr levels in groups S and B were significantly lower than those in group N, with significant statistical differences (P<0.05), but there was no significant difference in the Scr levels between groups S and B, indicating that both Shenshuai Pills and aldehyde-encapsulated starch have significant effects in reducing Scr, and the effect of Shenshuai Pills in reducing Scr is not inferior to aldehyde-encapsulated starch;

[0046] 3) The eGFR values ​​of group S and group B were significantly higher than those of group N, with significant statistical difference (P<0.05), but there was no significant difference in eGFR values ​​between group S and group B, indicating that both Shenshuai Pills and aldehyde-encapsulated starch can significantly delay the decline of eGFR, and the effect of Shenshuai Pills in delaying the decline of eGFR is not inferior to that of aldehyde-encapsulated starch;

[0047] 4) In patients with CKD stage 3, there was no significant difference in the [Ca]×[P] value among the groups; in patients with CKD stage 4, the [Ca]×[P] value of group S was significantly lower than that of group N, with a significant statistical difference (P<0.05), while the [Ca]×[P] value of group B was no different from that of group N, indicating that Shenshuai Pills has a significant effect in reducing the [Ca]×[P] value.

[0048] Security Analysis

[0049] Table 4 Adverse event records

[0050]

[0051] Note: S3 refers to patients in CKD stage 3 taking Shenshuai Pills, B3 refers to patients in CKD stage 3 taking Baodeoxy starch capsules, S4 refers to patients in CKD stage 3 taking Shenshuai Pills, and B4 refers to patients in CKD stage 4 taking Baodeoxy starch capsules.

[0052] The results showed that no serious adverse reactions occurred in any group during the entire clinical trial. There were 8 cases of adverse drug reactions in the S3 group, 6 cases of adverse reactions in the B3 group, 10 cases of adverse drug reactions in the S4 group, and 9 cases of adverse reactions in the B4 group, mainly nausea, vomiting, abdominal pain, diarrhea, cough, body aches, and increased blood pressure. All patients completed the trial and no special corrective treatment was used. There was no significant difference in the incidence of adverse events among the groups (P>0.05).

[0053] Clinical trial conclusion

[0054] The experiment proved that Shenshuai Pills, at the current dosage, can significantly reduce the Scr and UA levels of patients in CKD stage 3 and CKD stage 4, delay the decline of GRF, and correct the abnormality of bone metabolism, thereby protecting the remaining renal function, reducing complications, and delaying the progression of CKD, thereby prolonging the time for patients to enter end-stage renal disease and require replacement therapy, and relatively prolonging the long-term survival time of patients. In addition, compared with the drugs currently used for detoxification on the market, such as aldehyde-encapsulated starch, the clinical research results of this experiment suggest that the clinical treatment effects of the two drugs are similar, and the therapeutic effect of Shenshuai Pills is not inferior to that of aldehyde-encapsulated starch. In short, Shenshuai Pills have significant therapeutic effects on the treatment of CKD patients, and their price is favorable. Therefore, Shenshuai Pills are expected to become another type of drug that reduces Scr and delays the deterioration of renal function in addition to toxin adsorption drugs, providing more drug options for patients with various chronic nephritis and chronic renal failure. In addition, the research results also show that Shenshuai Pills have no obvious side effects and are highly safe. Therefore, Shenshuai Pills are suitable for patients with CKD caused by various reasons, and it is recommended to use them as early as possible to delay the progression of CKD.

[0055] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0056] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating CKD, characterized in that: The Chinese medicine composition comprises the following raw materials in parts by weight: 5-7 parts of leech, 5-7 parts of silkworm, 8.5-11.5 parts of rhubarb, and 45-55 parts of astragalus. The Chinese medicine composition can significantly reduce the Scr and UA levels of patients in CKD stage 3 and CKD stage 4, delay the decline of GRF, and correct the abnormal bone metabolism.

2. The use according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following raw materials in optimal weight proportions: 50 parts of astragalus, 10 parts of rhubarb, 6 parts of leech and 6 parts of bombyx batryticatus.

3. A Chinese medicine preparation for treating CKD, characterized in that: Including the Chinese medicine composition according to claim 1.

4. The method for preparing the Chinese medicine preparation according to claim 3, characterized in that: The process includes: 1) Grind 45-55 parts of Astragalus and 2.5-3.5 parts of Rhubarb through an 80-mesh sieve and set aside; 2) Add 200 mL of water to 5-7 parts of leeches and 5-7 parts of silkworms and boil for 45-60 minutes, filter and take the supernatant; add the remaining 6-8 parts of rhubarb to the residue and add 200 mL of water and boil for 45-60 minutes, filter and take the supernatant, combine the filtrates and concentrate to a density of 1.12-1.15; 3) Add astragalus powder and rhubarb powder, pass through a 10-mesh sieve, and granulate. Then, the pellets are molded, formed, covered, dried, selected, quality inspected, and packaged.

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