Traditional Chinese medicine composition for treating chronic kidney diseases and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating chronic kidney diseases and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials: fructus rosae laevigatae, semen euryales, radix astragali, radix puerariae, humifuse euphorbia herb and The preparation method comprises the following steps: crushing fructus rosae laevigatae, semen euryales, radix astragali, radix puerariae, humifuse euphorbia herb and serissa serissoide, and performing percolation extraction with ethanol. According to the traditional Chinese medicine composition, monarch drugs including fructus rosae laevigatae and semen euryales have the effects of tonifying kidney, securing essence and relieving enuresis, ministerial drugs including radix astragali and radix puerariae have the effects of tonifying spleen and promoting salivation, and adjuvant drugs including serissa japonica and humifuse euphorbia herb have the effects of clearing heat, promoting diuresis, detoxifying, promoting blood circulation, removing blood stasis and removing food retention, so that the whole prescription can nourish kidney yin, harmonize spleen and stomach and remove turbid evil, and the traditional Chinese medicine prescription which is rigorous in compatibility and synergistic in effect is realized; the effects of improving body weight, kidney function and blood fat level are obvious.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic kidney disease and application thereof. Background Art

[0002] Diabetic nephropathy is one of the chronic kidney diseases and one of the common and serious complications of diabetes. It has become the most common primary disease leading to end-stage renal disease worldwide. Once patients progress to ESRD, they need to receive renal replacement therapy, which seriously affects the patient's quality of life and brings a serious economic burden to the family and society. Therefore, research on the treatment of diabetic nephropathy has become a very serious problem. However, there is currently a lack of effective treatments for diabetic nephropathy. Therefore, it is crucial to seek new treatments to delay the development of diabetic nephropathy.

[0003] Traditional Chinese Medicine (TCM) boasts a rich and rich history. Herbal compound formulations are a hallmark of TCM treatment, often far surpassing the efficacy of individual herbs combined. Traditional Chinese medicine (TCM) prescriptions are the foundation of TCM treatment and its core. Many renowned and ancient formulas, proven through thousands of years of clinical practice, are widely recognized by doctors and patients for their efficacy.

[0004] Chinese invention patent application CN201710167762.4 discloses a traditional Chinese medicine preparation for treating diabetic nephropathy, as well as its preparation and administration methods. The preparation is composed of the following ingredients: astragalus root, pseudoginseng root, dodder seed, yam pulp, atractylodes macrocephala, kudzu root, euryale ferox, rosa laevigata fruit, cicada slough, euphratica root, patchouli root, rhubarb root, scutellaria baicalensis root, raw rehmannia root, Panax notoginseng powder, and salvia miltiorrhiza. The preparation is formulated based on Traditional Chinese Medicine theory, taking into account the characteristics of diabetic nephropathy and the extent of kidney damage, and adopting a syndrome differentiation and treatment approach. Long-term clinical observation has shown improvement in patients' clinical symptoms, with varying degrees of reduction in proteinuria, urea nitrogen, and serum creatinine, delaying the progression of nephropathy and improving renal function, achieving a dual therapeutic effect.

[0005] Chinese invention patent application 201210072427.3 discloses a traditional Chinese medicine for treating nephrotic syndrome, comprising Ganoderma lucidum, Astragalus membranaceus, Cordyceps sinensis powder, Psoralea corylifolia, Centella asiatica, stir-fried Atractylodes macrocephala, Chinese yam, safflower, Leonurus japonica, Panax notoginseng powder, Imperata cylindrica root, Thistle, Caulis cylindricae, Pyrrosia odorata, Rehmannia root, Cornus officinalis, Euryale ferox, Rosa laevigata fruit, Poria cocos, Scrophularia ningpoensis, Platycodon grandiflorum, Forsythia suspensa, and Licorice root. To prepare the decoction: Soak the ingredients in the decoction (except for the Cordyceps sinensis powder and Panax notoginseng powder) in a decoction pot for one hour in an appropriate amount of water, with the water level slightly above the surface of the ingredients. Bring the ingredients to a boil over high heat, then simmer for 25 minutes over low heat. Pour out the decoction. Repeat the decoction a second time and pour out the decoction. Combine the two decoctions for later use. Dosage: Take the decoction in equal doses, once in the morning and once in the evening, warm. Cordyceps sinensis powder and Panax notoginseng powder are divided into two equal parts and taken with the medicine in two doses.

[0006] Existing technologies have explored the treatment of chronic kidney disease and diabetic nephropathy to a certain extent, but firstly, the formulation is complex, and secondly, the therapeutic effect still has room for further improvement. Summary of the Invention

[0007] In view of the deficiencies in the prior art, the present invention provides a Chinese medicine composition for treating chronic kidney disease and its application.

[0008] In order to achieve the purpose of the present invention, the technical solutions adopted are as follows:

[0009] A traditional Chinese medicine composition for treating chronic kidney disease comprises the following ingredients: Rosa laevigata fruit, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Euphorbia milii and Serissa chinensis.

[0010] Preferably, the raw materials include the following components in parts by weight: 15-25 parts of Rosa laevigata fruit, 20-30 parts of Euryale ferox, 20-30 parts of Astragalus membranaceus, 10-15 parts of Pueraria root, 15-20 parts of Euphorbia milii and 15-25 parts of Psoralea corylifolia.

[0011] Preferably, the raw materials include the following components in parts by weight: 18-22 parts of Rosa laevigata fruit, 24-26 parts of Euryale ferox, 24-26 parts of Astragalus membranaceus, 14-15 parts of Pueraria root, 18-20 parts of Euphorbia milii and 16-20 parts of Psoralea corylifolia.

[0012] Preferably, the raw materials include the following components in parts by weight: 20 parts of Rosa laevigata fruit, 20 parts of Euryale ferox, 25 parts of Astragalus membranaceus, 15 parts of Pueraria root, 20 parts of Euphorbia milii and 18 parts of Psoralea corylifolia.

[0013] The second object of the present invention is to provide a method for preparing the Chinese medicine composition, comprising the following steps:

[0014] The product is obtained by grinding the fruit of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria root, Herba Euphorbiae rutaecarpa and Psoralea corylifolia, and extracting with ethanol.

[0015] Preferably, the amount of ethanol added is 8 to 12 times the total weight of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Euphorbia pulex and Psoralea corylifolia, the volume concentration of ethanol is 75-95%, and the extraction is further concentrated to obtain an extract.

[0016] Preferably, the extraction is performed 1 to 3 times, and the time for each extraction is 1 to 3 hours.

[0017] Preferably, the extract is further made into granules, and the particle size of the granules is 80-120 meshes.

[0018] The third object of the present invention is to provide a pharmaceutical preparation, the active ingredients of which include the traditional Chinese medicine composition, or the traditional Chinese medicine composition prepared according to the preparation method.

[0019] The fourth object of the present invention is to provide the use of the traditional Chinese medicine composition, or the traditional Chinese medicine composition prepared according to the preparation method, or the pharmaceutical preparation in the preparation of drugs for treating chronic kidney disease.

[0020] In some embodiments of the present invention, the traditional Chinese medicine composition, pharmaceutical composition or medicine can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, and lozenges. Suitable drug carriers in the art can be selected for different dosage forms.

[0021] The pharmaceutical carrier used can be a solid, liquid or gas. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0022] When preparing oral dosage compositions, any medium consistent with pharmaceutical formulation requirements can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, colorants, and the like can be used to form oral liquid formulations, such as suspensions and solutions; while carriers, such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, and disintegrants can be used to form oral solid formulations, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or nonaqueous techniques.

[0023] Tablets containing the Chinese medicine composition of the present invention can be prepared by tableting or molding, and one or more auxiliary ingredients or adjuvants can be used. The active ingredient can be compressed into a free-flowing form (such as powder or granules) in a suitable machine, and can be prepared by mixing with a binder, lubricant, inert diluent, surfactant or dispersant. Molded tablets can be molded in a suitable machine, i.e., a powdered mixture moistened with an inert liquid diluent, preferably containing about 0.05 mg to about 5 g of active ingredient per tablet, and preferably containing about 0.05 mg to about 5 g of active ingredient per sachet or capsule. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with an appropriate and convenient pharmaceutical carrier, which may account for about 5% to 95% of the total composition. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0024] The compositions of the present invention can be in a suitable form for use in transdermal drug delivery devices. These formulations can be prepared using the Chinese medicine compositions of the present invention by conventional processing methods. For example, a cream or ointment having a desired consistency can be prepared by mixing a hydrophilic material and water, and from about 5 wt % to about 10 wt % of the compound.

[0025] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, colorants and flavoring agents, etc., may be added, and the components containing the Chinese medicine composition of the present invention may also be prepared in the form of powder or concentrate.

[0026] Terms and Claims of the Present Invention:

[0027] The articles "a," "an," and "the" include plural referents unless expressly limited to one or more referents otherwise.

[0028] Unless otherwise expressly indicated, all ranges or ratios disclosed herein are to be understood to include any and all subranges or subratios contained therein. For example, a range or ratio stated as 1 to 30 is to be considered inclusive of any and all subranges or subratios, integers, decimals, or subranges or subratios comprised therein, between a minimum of 1 and a maximum of 30, and including any subranges or subratios, integers, decimals, or subranges or subratios comprised therein.

[0029] The terms "comprises," "includes," "have," "has," "may," "contain" and variations thereof are meant as open-ended conjunctions or terms that do not exclude the possibility of additional compositions or structures.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] This study adhered to the fundamental principles of Traditional Chinese Medicine (TCM) of "holistic thinking and syndrome differentiation and treatment" to tonify the kidney and replenish essence, strengthen the spleen and promote fluid production, clear heat and dampness, and activate blood circulation and resolve blood stasis. The main herbs, Rosa Laevigatae and Euryale ferox, tonify the kidney, consolidate essence, and stop nocturnal emission; the auxiliary herbs, Astragalus membranaceus and Pueraria root, tonify the spleen and promote fluid production; and the adjuvant herbs, Psoralea corylifolia and Herba Lycopodii, synergistically clear heat, dampness, and detoxify, while activating blood circulation, removing blood stasis, and eliminating accumulation. This formula's unique combination tonifies the kidney and replenishes essence while also tonifying the spleen and promoting fluid production, clearing heat and dampness, and activating blood circulation and removing blood stasis. This formula nourishes kidney yin, harmonizes the spleen and stomach, and eliminates turbid pathogens.

[0032] Pharmacological experiments have confirmed that the composition of the present invention can significantly treat chronic kidney disease, improve body weight level, blood creatinine level, urea nitrogen (BUN) level, urine creatinine level, urine protein level, urine protein creatinine ratio level, as well as triglyceride, high-density lipoprotein cholesterol, total cholesterol, alanine aminotransferase (ALT) levels, and can significantly reduce glomerular area. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The data show the changes in body weight and biochemical indicators of mice after 5 weeks of treatment. DKD, L, M, and H are the model group, the low-dose group of Example 1, the medium-dose group of Example 1, and the high-dose group of Example 1, respectively. Compared with the model group, ****P<0.0001, ***P<0.001, **P<0.01, and *P<0.05.

[0034] Figure 2 The changes in biochemical indicators of mice after 5 weeks of treatment, where DKD, L, M, and H are the model group, the low-dose group of Example 1, the medium-dose group of Example 1, and the high-dose group of Example 1, respectively. Compared with the model group, **P<0.01, *P<0.05.

[0035] Figure 3 The PAS staining results of kidney pathological sections after 5 weeks of treatment are shown, wherein DKD, L, M, and H are the model group, the low-dose group of Example 1, the medium-dose group of Example 1, and the high-dose group of Example 1, respectively.

[0036] Figure 4 The glomerular area of mice treated for 5 weeks, where DKD, L, M, and H are the model group, the low-dose group of Example 1, the medium-dose group of Example 1, and the high-dose group of Example 1, respectively. Compared with the model group, **P<0.01, *P<0.05.

[0037] Figure 5 The changes in biochemical indicators of mice treated for 8 weeks, where DKD 8 weeks and M 8 weeks were the model group and the 8-week treatment group were the dose group in Example 1. Compared with the model group, **P<0.01, *P<0.05.

[0038] Figure 6 The graph shows the PAS staining results of kidney pathological sections in 8 treated animals, wherein DKD 8 weeks and M 8 weeks are the model group, and the group treated for 8 weeks is the middle dose group in Example 1.

[0039] Figure 7 The glomerular area of mice treated for 8 weeks, compared with the model group, **P<0.01, *P<0.05. DETAILED DESCRIPTION

[0040] The present invention will be further described below in conjunction with specific embodiments. The following raw materials are all commercially available conventional raw materials.

[0041] Example 1

[0042] The composition provided in this embodiment has the following raw materials in parts by weight:

[0043] 20 parts of Rosa Laevigata Fruit, 25 parts of Euryale ferox, 25 parts of Astragalus

[0044] 15 parts of Pueraria root, 20 parts of Herba Euphorbiae chinensis, 18 parts of Psoralea corylifolia

[0045] The preparation method is as follows:

[0046] (1) Crush the fruit of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria root, Euphorbia milii, and Psoralea corylifolia, and extract with ethanol to obtain the product;

[0047] The amount of ethanol added is 8 times the total weight of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Euphorbia miltiorrhiza and Psoralea corylifolia, and the volume concentration of ethanol is 95% ethanol; the extraction time is 2 hours.

[0048] Example 2

[0049] The composition provided in this embodiment has the following raw materials in parts by weight:

[0050] 15 parts of Rosa Laevigata Fruit, 20 parts of Euryale ferox, 20 parts of Astragalus

[0051] 10 parts of Pueraria root, 15 parts of Herba Euphorbiae chinensis, 15 parts of Psoralea corylifolia

[0052] The preparation method is as follows:

[0053] (1) Crush the fruit of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria root, Euphorbia milii, and Psoralea corylifolia, and extract with ethanol to obtain the product;

[0054] The amount of ethanol added is 8 times the total weight of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Euphorbia miltiorrhiza and Psoralea corylifolia, and the volume concentration of ethanol is 85% ethanol; the extraction time is 3 hours.

[0055] Example 3

[0056] The composition provided in this embodiment has the following raw materials in parts by weight:

[0057] 25 parts of Rosa Laevigata Fruit, 30 parts of Euryale ferox, 30 parts of Astragalus

[0058] 15 parts of Pueraria root, 20 parts of Herba Euphorbiae chinensis, 25 parts of Psoralea corylifolia

[0059] The preparation method is as follows:

[0060] The formula granules of the above medicinal materials are mixed evenly and then taken orally after adding water.

[0061] 1. Pharmacodynamic Experimental Studies

[0062] Experiment 1: Effective drug concentration

[0063] 1.1 Animal modeling: Prepare experimental animals. Purchase 7-week-old C57BLKS / J (BKS) db / db male mice from Changzhou Cavens Animal Experiment Company. Adaptively raise them for 1 week. After observing that the mice are in good condition, the experimental mice are randomly grouped with reference to the random number table. Mice are randomly divided into a model control group (pure water), a low-dose group in Example 1, a medium-dose group in Example 1, and a high-dose group in Example 1, with 5 mice in each group. All are given normal feed and free access to food and water. The low-dose group in Example 1 is given 7.995g / kg / d by gavage, the medium-dose group is given 15.99g / kg / d by gavage, the high-dose group is given 31.98g / kg / d by gavage, and the model control group is given the same volume of pure water by gavage, and each is gavaged once a day for 5 consecutive weeks. At the same time, the blood glucose level of the mice is tested at the end of the second and fifth weeks after gavage, and the blood glucose level is not affected. On the last day of week 5, animals were anesthetized with 10% pentobarbital, and serum samples were collected for testing of relevant biochemical parameters, and feces were collected for fecal microbial 16S analysis. This experiment aimed to minimize the number of animals used and their suffering.

[0064] Detection indicators:

[0065] a. Biochemical test kits were used to detect cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum creatinine, blood urea nitrogen, urine protein, and urine creatinine levels.

[0066] b. PAS staining was used to detect renal pathological changes.

[0067] 1.2 Experimental Results

[0068] The results of biochemical index test, including weight level, blood creatinine level, blood urea nitrogen (BUN) level, urine creatinine level, urine protein level, and urine protein creatinine ratio level, are shown in Figure 1 , triglyceride, high-density lipoprotein cholesterol, alanine aminotransferase (ALT) test results as follows Figure 2 The test results of blood creatinine level, blood urea nitrogen level, urine protein, triglyceride, high-density lipoprotein cholesterol, and alanine aminotransferase (ALT) are shown in Table 1. The results show that after 5 weeks of administration of the composition of the present invention, the body weight level, blood creatinine level, blood urea nitrogen (BUN) level, urine protein level, triglyceride, high-density lipoprotein cholesterol ALT level of mice were significantly reduced to varying degrees.

[0069] Table 1

[0070]

[0071] Note: Compared with the model group, ****P<0.0001, ***P<0.001, **P<0.01, *P<0.05.

[0072] The results of PAS staining of kidney pathological sections after oral gavage treatment are shown in Figure 3 , the glomerular area of mice is shown in Figure 4 , **P<0.01, *P<0.05. Figure 4 It was found that the glomerular area of the mice in the Example 1 group was reduced.

[0073] Experiment 2: Time gradient experiment on the efficacy of the pharmaceutical composition of the present invention (administration for 8 weeks)

[0074] 2.1 Animal Modeling: Experimental animals were prepared by purchasing 7-week-old C57BLKS / J (BKS) db / db male mice from Changzhou Cavens Animal Laboratory Co., Ltd. They were acclimated for 1 week and observed to be in good condition. The mice were then randomly divided into groups according to a random number table. The mice were randomly divided into an 8-week model control group (purified water) and an 8-week dose group described in Example 1, with 5 mice in each group. All mice were fed a normal diet and had free access to food and water. The dose group described in Example 1 was administered 15.99 g / kg daily by gavage, while the model control group was administered the same volume of purified water by gavage once daily for 8 consecutive weeks. Simultaneously, the blood glucose levels of the mice were tested at the end of the 2nd, 4th, 6th, and 8th week after gavage (results showed little effect on blood glucose). On the last day of the 8th week, the mice were anesthetized with 10% pentobarbital, and serum samples from the 8-week-old mice were collected for testing of relevant biochemical indicators. The purpose of this experiment was to minimize the number of animals used and their suffering.

[0075] Test indicators: a. Biochemical kits to detect cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum creatinine, blood urea nitrogen, urine protein, and urine creatinine. b. PAS staining to detect renal pathological changes.

[0076] 2.2 Results of the time gradient experiment of drug efficacy

[0077] The results of biochemical index tests are shown in Table 2. Urine creatinine, urine protein creatinine, etc. Figure 5 The results showed that after 8 weeks of treatment, in addition to the improvement in the index levels in the 5th week of treatment, the levels of urine creatinine, urine protein creatinine ratio, and total cholesterol also improved further, with significant statistical differences compared with the control group.

[0078] Table 2

[0079]

[0080] The PAS results of kidney pathological sections after 8 weeks of JWSLEXDM gavage treatment were as follows: Figure 6-Figure 7Compared with the model group, after 8 weeks of treatment with the medium dose of Example 1, the glomerular area of the mice was significantly reduced, **P<0.01.

[0081] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for treating chronic kidney disease, characterized in that: Its raw materials include the following ingredients: Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Herba Euphorbiae chinensis and Serissa chinensis.

2. The Chinese medicine composition according to claim 1, characterized in that The raw materials include the following components in parts by weight: 15-25 parts of Rosa laevigata, 20-30 parts of Euryale ferox, 20-30 parts of Astragalus, 10-15 parts of Pueraria lobata, 15-20 parts of Herba Euphorbiae ivy and 15-25 parts of Psoralea corylifolia.

3. The Chinese medicine composition according to claim 1, characterized in that The raw materials include the following components in parts by weight: 18-22 parts of Rosa laevigata fruit, 24-26 parts of Euryale ferox, 24-26 parts of Astragalus membranaceus, 14-15 parts of Pueraria root, 18-20 parts of Euphorbia milii and 16-20 parts of Psoralea corylifolia.

4. The Chinese medicine composition according to claim 1, characterized in that The raw materials include the following components in parts by weight: 20 parts of Rosa laevigata fruit, 20 parts of Euryale ferox, 25 parts of Astragalus membranaceus, 15 parts of Pueraria root, 20 parts of Euphorbia milii and 18 parts of Psoralea corylifolia.

5. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The steps include: The product is obtained by crushing the fruits of Rosa laevigata, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Herba Euphorbiae rutaecarpa and Serissa chinensis, and then boiling them with water for extraction or percolating with ethanol for extraction.

6. The preparation method according to claim 5, characterized in that The amount of ethanol in the ethanol percolation extraction is 8 to 12 times the total weight of the Rosa laevigata fruit, Euryale ferox, Astragalus membranaceus, Pueraria lobata, Euphorbia miltiorrhiza and Psoralea corylifolia, and the volume concentration of the ethanol is 75 to 95%. After the extraction, the extract is further concentrated to obtain an extract.

7. The preparation method according to claim 6, characterized in that The extraction is performed 1 to 3 times, and the time for each extraction is 1 to 3 hours.

8. The preparation method according to claim 6, characterized in that The extract is further made into granules with a particle size of 80-120 meshes.

9. A pharmaceutical preparation, characterized in that The effective ingredients thereof include the traditional Chinese medicine composition according to any one of claims 1 to 4, or the traditional Chinese medicine composition prepared according to the preparation method according to any one of claims 5 to 7.

10. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4, or the traditional Chinese medicine composition prepared according to the preparation method according to any one of claims 5 to 7, or the pharmaceutical preparation according to any one of claims 8 to 9 in the preparation of a drug for treating chronic kidney disease or diabetic nephropathy.

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