Traditional Chinese medicine composition for treating diabetic nephropathy as well as preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating diabetic nephropathy as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 250 to 400 parts of radix astragali seu hedysari, 350 to 500 parts of radix rehmanniae recen, 200 to 350 parts of rhizoma atractylodis macrocephalae stir-fried with bran, 50 to 200 parts of radix et rhizoma rhei, 200 to 350 parts of herba leonuri, 200 to 350 parts of radix angelicae sinensis, 200 to 350 parts of cortex phellodendri and 30 to 120 parts of scalded leech. Compared with radix astragali and rhizoma atractylodis macrocephalae capsules, the traditional Chinese medicine composition disclosed by the invention can more effectively reduce fasting blood glucose, blood urea nitrogen and serum creatinine of rats with diabetic nephropathy.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating diabetic nephropathy, a preparation method thereof, and an application thereof. Background Art

[0002] Diabetic kidney disease (DKD) is the most common and intractable microvascular complication of diabetes and one of the main causes of death in diabetic patients. Once it develops into end-stage renal disease, the prognosis is extremely poor. A traditional Chinese medicine compound is formulated under the guidance of traditional Chinese medical thinking methods. Through the four diagnostic methods (inspection, auscultation and olfaction, interrogation, and palpation), the syndrome is identified, the medicinal flavors are selected, and the compound is composed according to the compatibility principles of monarch, minister, assistant, and guide, so as to regulate the balance of the human body and the homeostasis of the internal environment as a whole.

[0003] The literature "Li Zini, Li Tingting, Zhao Yirui. Discussion on the regulatory effect of Qizhu Capsule on the tricarboxylic acid cycle in rats with diabetic nephropathy [J]. Chinese Journal of Integrated Traditional and Western Nephrology, 2022(4). DOI: 10.3969 / j.issn.1009-587X.2022.04.019." discloses that Qizhu Capsule (Traditional Chinese Medicine Preparation Approval Number in Shanxi Province: AZ20080200, composed of Astragalus membranaceus, Angelica sinensis, Atractylodes lancea, Phellodendron amurense, Hirudo, Pheretima, and Rheum palmatum) is a pharmaceutical preparation that has been continuously refined and screened on the basis of being clinically effective for more than a decade according to the method of strengthening the spleen and promoting blood circulation, clearing heat and drying dampness, and is applicable to patients with early and middle-stage diabetic nephropathy. However, in terms of reducing fasting blood glucose, blood urea nitrogen, and serum creatinine, the therapeutic effect of Qizhu Capsule is inferior to the traditional Chinese medicine composition disclosed in the present invention.

[0004] Chinese Patent CN108853433A discloses a traditional Chinese medicine for treating diabetic nephropathy and a preparation method thereof. The traditional Chinese medicine for treating diabetic nephropathy is prepared by mixing the following raw materials in certain parts by weight: Astragalus membranaceus, Angelica sinensis, Dioscorea opposita, Salvia miltiorrhiza, Codonopsis pilosula, Paeonia lactiflora, Leonurus japonicus, Rosa laevigata, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Carthamus tinctorius, Ligusticum wallichii, Cuscuta chinensis, Achyranthes bidentata, Hirudo, Pheretima, Panax notoginseng, Rheum palmatum, Poria cocos, Alisma orientale, Erigeron breviscapus, Gynostemma pentaphyllum, Tripterygium wilfordii, Corn silk, Euphorbia humifusa, Curcuma longa, and Rhodiola rosea. However, this patent does not study the effect of this traditional Chinese medicine composition on reducing blood urea nitrogen and serum creatinine.

[0005] Chinese Patent CN112336819A discloses a traditional Chinese medicine for treating diabetes and its complications. The traditional Chinese medicine comprises the following components: astragalus membranaceus, trichosanthes kirilowii maxim, asparagus cochinchinensis, ophipogon japonicus, atractylodes lancea, rhizoma dioscoreae, rehmannia glutinosa, salvia miltiorrhiza, pueraria lobata, radix paeoniae rubra, pure honey, schizandra chinensis, glycyrrhiza uralensis, rehmannia glutinosa, wolfberry fruit, stir-fried plastron carapacis, taxillus chinensis, stir-fried eucommia ulmoides, dipsacus asperoides, cyathula officinalis, cibotium barometz, angelica sinensis, radix paeoniae alba, ligusticum wallichii, myrrh, pilose antler, psoralea corylifolia, drynaria fortunei, safflower, vitex trifolia, gleditsia sinensis, luffa cylindrica, roasted astragalus membranaceus, perilla frutescens, stir-fried atractylodes macrocephala, cyperus rotundus, lindera aggregata, rhizoma corydalis, bupleurum chinense, leonurus japonicus, smilax glabra, caulis sargentodoxae, coix lacryma-jobi, indigo naturalis, magnolia liliflora, isatis indigotica, honeysuckle, prunella vulgaris, phellodendron amurense, coptis chinensis, rheum officinale, gentiana scabra, wild chrysanthemum, plantago asiatica, balsam pear root, gallnut, cortex pseudolaricis, polygonum multiflorum and glochidion puberum. However, the patent does not study the effects of this traditional Chinese medicine composition on reducing fasting blood glucose, blood urea nitrogen and serum creatinine.

[0006] Chinese Patent CN106975030A discloses a fermented traditional Chinese medicine preparation, its preparation method and application. The fermented traditional Chinese medicine preparation is obtained by fermenting pleurotus ostreatus in traditional Chinese medicine raw materials. The traditional Chinese medicine raw materials are as follows in parts by weight: 10-100 parts of cinnamon, 10-100 parts of dendrobium officinale, 10-100 parts of trichosanthes kirilowii maxim, 10-100 parts of alisma orientale, 10-100 parts of pueraria lobata, 10-100 parts of polyporus umbellatus, 10-100 parts of poria cocos, 10-100 parts of balsam pear, 10-100 parts of rhizoma dioscoreae, 10-100 parts of astragalus membranaceus, 6-60 parts of anemarrhena asphodeloides, 6-60 parts of polygonatum sibiricum, 6-60 parts of oyster, 6-60 parts of coix lacryma-jobi, 6-60 parts of peach kernel, 6-60 parts of scutellaria baicalensis, 6-60 parts of pheretima aspergillum, 6-60 parts of endoconcha seu endospermum amygdalae, 6-60 parts of angelica sinensis, 6-60 parts of licorice, 4-40 parts of bombyx batryticatus, 4-40 parts of atractylodes macrocephala, 4-40 parts of gardenia jasminoides, 4-40 parts of leonurus japonicus, 4-40 parts of rehmannia glutinosa, 4-40 parts of cortex lycii radicis, 4-40 parts of epimedium brevicornu, 4-40 parts of cicada flower, 2-20 parts of rheum officinale, 2-20 parts of phellodendron amurense, 2-20 parts of atractylodes lancea, 2-20 parts of cuscutae semen, 2-20 parts of semen astragali complanati, 2-20 parts of codonopsis pilosula, 2-20 parts of eupatorium japonicum, 2-20 parts of arctium lappa, 2-20 parts of schizandra chinensis, 2-20 parts of jujube, 2-20 parts of coptis chinensis, 1-10 parts of whitmania pigra, 1-10 parts of ophipogon japonicus, 1-10 parts of scrophularia ningpoensis, 1-10 parts of radix paeoniae rubra, 1-10 parts of pseudostellaria heterophylla, 1-10 parts of cyathula officinalis, 1-10 parts of asparagus cochinchinensis, 1-10 parts of fructus mume; pleurotus ostreatus accounts for 5%-10% of the mass of the traditional Chinese medicine raw materials. The fermented traditional Chinese medicine preparation provided by the invention has good effects in treating and curing diabetes. However, the key innovation point of the fermented traditional Chinese medicine preparation is the fermentation step, and the traditional Chinese medicine composition is not optimized.

[0007] In view of this, to solve the deficiencies of the prior art, the present invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, its preparation method and application. Summary of the Invention

[0008] In view of this, the object of the present invention is to provide a traditional Chinese medicine composition for treating diabetic nephropathy, its preparation method and application, and this traditional Chinese medicine composition can significantly reduce the fasting blood glucose, blood urea nitrogen and serum creatinine of rats with diabetic nephropathy.

[0009] To achieve the above object of the invention, the technical solution of the present invention is as follows:

[0010] On the one hand, the present invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, and the traditional Chinese medicine composition comprises the following components in parts by weight: 250 - 400 parts of Astragalus membranaceus, 350 - 500 parts of Rehmannia glutinosa, 200 - 350 parts of stir-fried Atractylodes macrocephala with bran, 50 - 200 parts of Rheum palmatum, 200 - 350 parts of Leonurus japonicus, 200 - 350 parts of Angelica sinensis, 200 - 350 parts of Phellodendron amurense, 30 - 120 parts of leech.

[0011] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 300 - 350 parts of Astragalus membranaceus, 400 - 450 parts of Rehmannia glutinosa, 250 - 300 parts of stir-fried Atractylodes macrocephala with bran, 100 - 150 parts of Rheum palmatum, 250 - 300 parts of Leonurus japonicus, 250 - 300 parts of Angelica sinensis, 250 - 300 parts of Phellodendron amurense, 50 - 100 parts of leech.

[0012] More preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 326 parts of Astragalus membranaceus, 435 parts of Rehmannia glutinosa, 261 parts of stir-fried Atractylodes macrocephala with bran, 130 parts of Rheum palmatum, 261 parts of Leonurus japonicus, 261 parts of Angelica sinensis, 261 parts of Phellodendron amurense, 65 parts of leech.

[0013] On the other hand, the present invention provides a preparation method of the above traditional Chinese medicine composition, comprising the following steps:

[0014] (1) Extract the medicinal materials in a formula amount with water to obtain an extract;

[0015] (2) Concentrate the extract under reduced pressure into a clear paste, and dry it to obtain the traditional Chinese medicine composition.

[0016] Preferably, the preparation method comprises the following steps:

[0017] (1) Heat and reflux extract the medicinal materials in a formula amount with water for 1 - 3 times, add 8 - 17 times the weight of water to the medicinal materials each time, and extract for 0.5 - 1.5 hours each time to obtain an extract;

[0018] (2) Concentrate the extract under reduced pressure to a clear paste with a relative density of 1.05 - 1.10 (60 °C), and dry it to obtain the traditional Chinese medicine composition.

[0019] More preferably, the preparation method comprises the following steps:

[0020] (1) Add the medicinal materials in the formula amount and extract them by heating under reflux with water twice. For the first time, add 14 times the weight of water to the medicinal materials and extract for 1.5 hours; for the second time, add 11 times the weight of water to the medicinal materials and extract for 1.5 hours to obtain the extraction solution.

[0021] (2) Concentrate the extraction solution under reduced pressure to obtain a clear paste with a relative density of 1.05 - 1.10 (60 °C), and spray dry it to obtain the traditional Chinese medicine composition.

[0022] On the other hand, the present invention provides a drug, and the drug comprises the above-mentioned traditional Chinese medicine composition.

[0023] The drug can be prepared into dosage forms for administration such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, troches, etc., and suitable pharmaceutical carriers in the art can be selected according to different dosage forms.

[0024] The pharmaceutical carriers used can be 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 gas carriers include carbon dioxide and nitrogen.

[0025] When preparing the composition in an oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agent, preservative, coloring agent, etc. can be used to form oral liquid preparations such as suspensions and solutions; while carriers such as starch, sugar, microcrystalline cellulose, diluent, granulating agent, emulsifier, lubricant, binder, disintegrant can be used to form oral solid preparations such as powders, capsules and tablets. Due to their easy administration, tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers. Standard aqueous or non-aqueous techniques can be selected for coating the tablets.

[0026] Tablets containing the traditional Chinese medicine composition of the present invention can be prepared by tabletting or molding, and one or more auxiliary components or adjuvants can be optionally used. The active ingredient can be tabletted in a free-flowing form (such as powder or granules) in a suitable machine, optionally mixed with binders, lubricants, inert diluents, surface active substances or dispersants to prepare the tablets. Molded tablets can be molded in a suitable machine, namely a mixture of powdered compounds moistened with an inert liquid diluent. Each tablet preferably contains about 0.05 mg to about 5 g of the active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of the active ingredient. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of the active drug, mixed with a suitable and convenient carrier material, which may account for about 5% to 95% of the total composition. The unit dosage form usually contains about 1 mg to about 2 g of the active ingredient, usually 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0027] The pharmaceutical composition suitable for parenteral administration in the present invention can be prepared as an aqueous solution or suspension of the active compound. Appropriate surfactants can be included, such as hydroxypropyl cellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and their oil mixtures. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0028] The drugs of the present invention can be in a form suitable for topical use, such as aerosols, creams, ointments, lotions, powders or the like. In addition, the composition can be in a suitable form for a transdermal delivery device. The traditional Chinese medicine composition of the present invention can be used to prepare these prescriptions by conventional processing methods. For example, creams or ointments with the desired consistency are prepared by mixing hydrophilic materials and water, and about 5 wt% to about 10 wt% of the compound.

[0029] The drugs of the present invention can be in a form suitable for rectal administration, where the carrier is solid. It is preferably to make the mixture into unit-dose suppositories. Suitable carriers include cocoa butter and other commonly used materials in the art. The suppositories can be prepared by first forming a composition containing a softened or melted carrier, and then cooling and shaping in a mold.

[0030] In addition to the above carrier components, the above pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surface active substances, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients can be added, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc., coloring agents and flavoring agents, etc. To make the preparation isotonic with the blood of the intended recipient. The components containing the traditional Chinese medicine composition of the present invention can also be prepared in the form of powders or concentrates.

[0031] Preferably, the drug is an oral pharmaceutical preparation.

[0032] More preferably, the oral pharmaceutical preparation is any one of decoctions, pills, tablets, capsules, powders, granules, oral liquids.

[0033] Even more preferably, the oral pharmaceutical preparation is granules.

[0034] Preferably, the oral pharmaceutical preparation further contains excipients.

[0035] More preferably, the type of excipients contained in the oral pharmaceutical preparation is dextrin, and the content is 6-14%.

[0036] Finally, the present invention provides the use of the above traditional Chinese medicine composition in the preparation of a drug for treating diabetic nephropathy.

[0037] The beneficial effects of the present invention are as follows:

[0038] (1) Compared with Qizhu capsules, the traditional Chinese medicine composition disclosed by the present invention can more effectively reduce the fasting blood glucose, blood urea nitrogen and serum creatinine of rats with diabetic nephropathy.

[0039] (2) The present invention defines that the weight ratio of astragalus membranaceus, rehmannia glutinosa, stir-fried atractylodes macrocephala, rhubarb, leonurus japonicus, angelica sinensis, phellodendron amurense, and leech is 250-400:350-500:200-350:50-200:200-350:200-350:200-350:30-120, so as to effectively reduce the fasting blood glucose, blood urea nitrogen and serum creatinine of rats with diabetic nephropathy. Detailed implementation mode

[0040] The following non-limiting examples can enable those of ordinary skill in the art to more comprehensively understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the invention of the present invention according to the disclosed content, and it should also fall within the scope claimed by the present invention.

[0041] The present invention will be further described below by way of specific examples. All kinds of chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all mass contents. Unless otherwise specified, it is understood that the operations are carried out at room temperature.

[0042] Compatibility relationship: In the formula, Astragalus membranaceus is sweet in flavor and warm in nature, replenishing qi, strengthening the spleen and benefiting the lungs. Rehmannia glutinosa clears heat and cools the blood, nourishes yin and promotes blood circulation. The two are used together as the monarch drugs. Atractylodes macrocephala replenishes qi, strengthens the spleen and dries dampness. Rheum palmatum purges downward, disperses stasis and reduces turbidity. The two assist the monarch drugs and act as the minister drugs. Leonurus japonicus promotes blood circulation to remove stasis, promotes diuresis and reduces swelling. Angelica sinensis nourishes blood and promotes blood circulation. Phellodendron amurense clears heat and dries dampness. Hirudo breaks blood stasis and dredges menstruation. The four together act as the assistant drugs. All the drugs are used together to achieve the effects of replenishing qi and strengthening the spleen, promoting blood circulation and promoting diuresis.

[0043] Astragalus membranaceus is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the Leguminosae family. It is dug in spring and autumn, the fibrous roots and root tips are removed, and then it is dried in the sun. It has the effects of replenishing qi and ascending yang, securing the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting the production of body fluid and nourishing blood, promoting qi movement and dredging collaterals, expelling pus and toxin through supplementation, and astringing sores and promoting granulation. It is used for qi deficiency with weakness, poor appetite and loose stools, middle qi sinking, chronic diarrhea and rectal prolapse, hematochezia and metrorrhagia, spontaneous sweating due to exterior deficiency, qi deficiency edema, internal heat with polydipsia, blood deficiency with sallow complexion, hemiplegia, numbness and pain in the bi syndrome, carbuncles and sores that are difficult to ulcerate, and chronic ulcers that do not heal.

[0044] Rehmannia glutinosa is the dried tuberous root of Rehmannia glutinosa Libosch. of the Scrophulariaceae family. It is dug in autumn, the rhizome tip, fibrous roots and sediment are removed, and then it is slowly baked until it is about 80% dry. It has the effects of clearing heat and cooling the blood, nourishing yin and promoting the production of body fluid. It is used for heat entering nutrient-blood aspect, epidemic febrile disease with toxin-induced maculae, hematemesis and epistaxis, febrile disease injuring yin, crimson tongue with restlessness and thirst, body fluid injury with constipation, yin deficiency fever, steaming bone fever, and internal heat with polydipsia.

[0045] Atractylodes macrocephala stir-fried with bran: The honey-roasted bran is scattered into a hot wok. When it smokes, add Atractylodes macrocephala slices and stir-fry until they turn yellowish brown and emit a burnt aroma, then take them out and sift out the honey-roasted bran. For every 100 kg of Atractylodes macrocephala slices, 10 kg of honey-roasted bran is used. It has the effects of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and preventing miscarriage. It is used for poor appetite due to spleen deficiency, abdominal distension and diarrhea, dizziness and palpitation due to phlegm-fluid retention, edema, spontaneous sweating, and restlessness during pregnancy.

[0046] Rheum palmatum is the dried root and rhizome of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. of the Polygonaceae family. It is dug in late autumn when the stems and leaves wither or before germination in the next spring. The fine roots are removed, the outer bark is scraped off, cut into slices or segments, strung together with ropes and dried or directly dried. It has the effects of purging downward to relieve accumulation, clearing heat and purging fire, cooling blood and detoxifying, removing stasis and dredging menstruation, promoting diuresis and reducing jaundice. It is used for constipation due to accumulation of heat in excess, hematemesis and epistaxis due to blood heat, red eyes and swollen throat, carbuncles and sores, appendicitis with abdominal pain, amenorrhea due to blood stasis, postpartum stasis obstruction, traumatic injury, damp-heat dysentery, jaundice with reddish urine, stranguria syndrome, and edema.

[0047] Motherwort is the fresh or dried aerial part of Leonurus japonicus Houtt., a plant of the Labiatae family. Fresh products are harvested from the seedling stage in spring to the pre-flowering stage in early summer; dried products are harvested in summer when the stems and leaves are lush and the flowers have not yet bloomed or have just bloomed, and then sun-dried or cut into sections and sun-dried. It has the effects of promoting blood circulation and regulating menstruation, promoting diuresis and reducing swelling, and clearing away heat and detoxifying. It is used for irregular menstruation, dysmenorrhea, amenorrhea, lochia retention, edema, oliguria, and sores and swelling.

[0048] Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels, a plant of the Umbelliferae family. It is dug up in late autumn, the fibrous roots and mud are removed, and after the water evaporates slightly, it is tied into small bundles, put on a shed, and slowly smoked dry with fireworks. It has the effects of nourishing blood and activating blood circulation, regulating menstruation and relieving pain, and moistening the intestines and relieving constipation. It is used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, injuries from falls, carbuncles and ulcers, and constipation due to dry intestines.

[0049] Phellodendron chinense Schneid. is a dried bark of the Rutaceae plant. It is commonly known as "Sichuan Phellodendron". After peeling the bark, remove the rough skin and dry it in the sun. It has the effects of clearing away heat and dampness, purging fire and removing steam, detoxifying and curing sores. It is used for damp-heat diarrhea, jaundice and red urine, vaginal itching due to vaginal discharge, painful stranguria due to heat, beriberi and paralysis, bone steaming and fatigue fever, night sweats, spermatorrhea, sores and swelling, eczema and wet sores.

[0050] Scald leeches, take clean leech segments, and scald them with talcum powder until they swell slightly according to the stir-fry method (General Chapter 0213 of the 2020 edition of the Chinese Pharmacopoeia). It has the effects of breaking blood and promoting menstruation, removing blood stasis and eliminating symptoms. It is used for blood stasis, amenorrhea, lumps and masses, hemiplegia caused by stroke, and injuries caused by falls.

[0051] Poria cocos is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf. It is usually dug from July to September, after which the sand is removed, piled up to "sweate", spread out to air dry on the surface, and then "sweated" again, repeatedly several times until wrinkles appear and most of the internal moisture is lost, and then dried in the shade, which is called "Poria cocos pieces"; or fresh Poria cocos is cut into different parts and dried in the shade, which are called "Poria cocos blocks" and "Poria cocos slices" respectively.

[0052] Earthworms are the dried bodies of Pheretima aspergillum (E.Perrier), Pheretima vulgaris Chen, Pheretima guillelmi (Michaelsen) or Pheretima pectinifera Michaelsen. The former is commonly known as Guangdilong, and the latter three are commonly known as Shanghaidilong. Guangdilong is caught from spring to autumn, and Shanghaidilong is caught in summer. The abdomen is opened in time, the internal organs and mud and sand are removed, washed, and dried in the sun or at low temperature.

[0053] Atractylodes rhizome is the rhizome of Atractylodes lancea (Thunb.) DC. var. lancea or Atractylodes chinensis (DC.) Koidz. etc. of the Compositae family. It can be dug in spring or autumn, preferably in autumn. After digging out the rhizome, remove the residual stems, fibrous roots and soil, and dry in the sun.

[0054] Codonopsis pilosula is the dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen or Codonopsis tangshen Oliv. of the Campanulaceae family. It is dug in autumn, washed and dried in the sun.

[0055] Example 1

[0056] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum palmatum, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot water is 326:435:261:130:261:261:261:65.

[0057] Preparation method:

[0058] Mix all the raw materials, add water with a weight 14 times that of all the raw materials and decoct for 1.5 hours, filter the decoction, then add water with a weight 11 times that of all the raw materials and decoct for 1.5 hours, filter the decoction, combine the filtrates of the two decoctions, concentrate under reduced pressure to a clear paste with a relative density of 1.05 - 1.10 (60 °C), add dextrin, with the addition amount being 3% of the total weight of the raw materials, mix evenly, spray-dry, then add dextrin with an amount of 7% of the total weight of the raw materials, mix evenly, make into granules, and you will get the product.

[0059] Example 2

[0060] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum palmatum, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot water is 300:400:250:150:300:300:250:50.

[0061] The preparation method is the same as that of Example 1.

[0062] Example 3

[0063] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum palmatum, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot water is 350:450:300:100:250:250:300:100.

[0064] The preparation method is the same as that of Example 1.

[0065] Example 4

[0066] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 250:350:200:200:350:350:350:30.

[0067] The preparation method is the same as that of Example 1.

[0068] Example 5

[0069] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 400:500:350:50:200:200:200:120.

[0070] The preparation method is the same as that of Example 1.

[0071] Comparative Example 1

[0072] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 326:435:400:50:400:200:261:65.

[0073] The preparation method is the same as that of Example 1.

[0074] Comparative Example 2

[0075] The weight ratio of Astragalus membranaceus, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 761:261:130:261:261:261:65.

[0076] The preparation method is the same as that of Example 1.

[0077] Comparative Example 3

[0078] The weight ratio of Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 761:261:130:261:261:261:65.

[0079] The preparation method is the same as that of Example 1.

[0080] Comparative Example 4

[0081] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes macrocephala Koidz. stir-fried with bran, Rheum officinale, Leonurus japonicus, Angelica sinensis, and Hirudo nipponia Whitman stir-fried with hot sand is 326:435:261:130:377:377:94.

[0082] The preparation method is the same as that of Example 1.

[0083] Comparative Example 5

[0084] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, Atractylodes lancea, Rheum officinale, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, and Hirudo nipponia Whitman stir-fried with hot sand is 326:435:261:130:261:261:261:65.

[0085] The preparation method is the same as that of Example 1.

[0086] Comparative Example 6

[0087] The weight ratio of Astragalus membranaceus, Atractylodes lancea, Angelica sinensis, Hirudo, Rheum palmatum, Phellodendron amurense, and Pheretima aspergillum is 326:261:261:65:130:261:300.

[0088] The preparation method is the same as that of Example 1.

[0089] Comparative Example 7

[0090] The weight ratio of Astragalus membranaceus, Rehmannia glutinosa, stir-fried Atractylodes macrocephala with bran, Rheum palmatum, Leonurus japonicus, Angelica sinensis, Phellodendron amurense, leech parched with vinegar, Poria cocos, Pheretima aspergillum, Atractylodes lancea, and Codonopsis pilosula is 326:435:261:130:261:261:261:65:500:300:100:100.

[0091] The preparation method is the same as that of Example 1.

[0092] 1. Extraction experiment

[0093] Taking the extract yield and content as the evaluation indexes of the experiment, the water addition amount (A), decoction time (B), and decoction times (C) are the three main factors affecting extraction, and the extract yield and content of the test samples are measured.

[0094] The factor level table of the experiment is shown in Table 1.

[0095] Table 1

[0096]

[0097] Experiment 1: Weigh a total of 46.80 g of raw materials according to the weight ratio in Example 1, add 11 times the weight of water of the raw materials and decoct for 0.5 hour, filter the decoction, record the volume, measure the solid content, and calculate the extract yield. Extract yield % = solid content (g / mL) × filtrate volume (mL) / raw material weight (g) × 100%. At the same time, according to the content determination method of Astragalus membranaceus in Part I of the Chinese Pharmacopoeia 2020 Edition, detect the content of calycosin-7-O-β-D-glucoside in the solid content.

[0098] Experiment 2: Weigh a total of 46.31 g of raw materials according to the weight ratio in Example 1, add 11 times the weight of water of the raw materials and decoct for 1 hour, filter the decoction, then add 8 times the weight of water of the raw materials and decoct for 1 hour, filter the decoction, combine the filtrates of the two decoctions, record the volume, measure the solid content, and calculate the extract yield. Extract yield % = solid content (g / mL) × filtrate volume (mL) / raw material weight (g) × 100%. At the same time, according to the content determination method of Astragalus membranaceus in Part I of the Chinese Pharmacopoeia 2020 Edition, detect the content of calycosin-7-O-β-D-glucoside in the solid content.

[0099] Experiment 3: Weigh a total of 46.66 g of raw materials according to the weight ratio in Example 1, add water 11 times the weight of the raw materials, decoct for 1.5 hours, filter the decoction liquid, then add water 8 times the weight of the raw materials and decoct for 1.5 hours, filter the decoction liquid, and then add water 8 times the weight of the raw materials and decoct for 1.5 hours, filter the decoction liquid. Combine the three decoction filtrates, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragali Radix in Part I of the Chinese Pharmacopoeia 2020 edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0100] Experiment 4: Weigh a total of 46.37 g of raw materials according to the weight ratio in Example 1, add water 14 times the weight of the raw materials and decoct for 0.5 hours, filter the decoction liquid, then add water 11 times the weight of the raw materials and decoct for 0.5 hours, filter the decoction liquid. Combine the two decoction filtrates, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragali Radix in Part I of the Chinese Pharmacopoeia 2020 edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0101] Experiment 5: Weigh a total of 46.73 g of raw materials according to the weight ratio in Example 1, add water 14 times the weight of the raw materials and decoct for 1 hour, filter the decoction liquid, then add water 11 times the weight of the raw materials and decoct for 1 hour, filter the decoction liquid, and then add water 11 times the weight of the raw materials and decoct for 1 hour, filter the decoction liquid. Combine the three decoction filtrates, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragali Radix in Part I of the Chinese Pharmacopoeia 2020 edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0102] Experiment 6: Weigh a total of 46.32 g of raw materials according to the weight ratio in Example 1, add water 14 times the weight of the raw materials and decoct for 1.5 hours, filter the decoction liquid, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragali Radix in Part I of the Chinese Pharmacopoeia 2020 edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0103] Experiment 7: Weigh a total of 46.31 g of raw materials according to the weight ratio in Example 1, add water 17 times the weight of the raw materials and decoct for 0.5 hour. Filter the decoction, then add water 14 times the weight of the raw materials and decoct for 0.5 hour. Filter the decoction, then add water 14 times the weight of the raw materials and decoct for 0.5 hour. Filter the decoction. Combine the filtrates of the three decoctions, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragalus membranaceus in Part I of the Chinese Pharmacopoeia 2020 Edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0104] Experiment 8: Weigh a total of 46.28 g of raw materials according to the weight ratio in Example 1, add water 17 times the weight of the raw materials and decoct for 1 hour. Filter the decoction, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragalus membranaceus in Part I of the Chinese Pharmacopoeia 2020 Edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0105] Experiment 9: Weigh a total of 46.28 g of raw materials according to the weight ratio in Example 1, add water 17 times the weight of the raw materials and decoct for 1.5 hours. Filter the decoction, then add water 14 times the weight of the raw materials and decoct for 1.5 hours. Filter the decoction. Combine the filtrates of the two decoctions, record the volume, measure the solids, and calculate the paste yield. Paste yield % = Solids (g / mL) × Filtrate volume (mL) / Raw material weight (g) × 100%. At the same time, according to the content determination method of Astragalus membranaceus in Part I of the Chinese Pharmacopoeia 2020 Edition, detect the content of calycosin-7-O-β-D-glucoside in the solids.

[0106] The experimental results are shown in Table 2.

[0107] Table 2

[0108]

[0109] The comprehensive score of each factor level is shown in Table 3.

[0110] Table 3

[0111] Water addition amount A Decoction time B Decoction times C Sum of level 1 209.08 195.21 165.75 Sum of level 2 219.69 196.86 224.55 Sum of level 3 222.44 258.24 260.91

[0112] For the comprehensive score of each level of water addition amount, level 1 < level 2 < level 3, and the gap between level 2 and level 3 is relatively small, while the gap with level 1 is relatively large;

[0113] For the comprehensive score of each level of decocting time, level 1 < level 2 < level 3, and the gap between level 3 and level 1, level 2 is relatively large;

[0114] The comprehensive scores of each level of decoction times were such that level 1 < level 2 < level 3, and the gap between level 2 and level 3 was relatively small.

[0115] Considering reducing energy consumption, reducing costs, and simplifying the process, the optimal extraction process combination was A2B3C2, that is, the water addition was 11 times, decocted 2 times, each decoction for 1.5 hours, and 3 times the amount of water was added in the first decoction.

[0116] 2. Animal experiments

[0117] SD rats, weighing 180 - 220 g, were divided into a normal group and a model group after adaptive feeding. The rats in the model group were fed a high-fat diet (including 71.5% basal diet, 10% lard, 10% egg yolk, 5% glucose, 2.5% milk powder, 1% cholesterol) for 4 weeks. During the same period, the rats in the normal group were fed a normal diet. Then, the rats in the model group were intraperitoneally injected with a 1% concentration of STZ solution at 65 mg / kg (streptozotocin, dissolved in 0.1 mol / L sodium citrate buffer under low temperature and light - avoiding environment, pH 4.5), and the rats in the normal group were injected with an equal volume of sodium citrate buffer. Three days later, blood was taken from the tail vein of the rats in the model group, and the fasting blood glucose of the rats was measured ≥16.7 mmol / L, indicating successful establishment of the rat diabetes model. The rats in the model group continued to be fed the high - fat diet for 2 weeks, and the total urinary protein of the rats was detected ≥30 mg / 24 h, indicating successful preparation of the rat diabetic nephropathy model.

[0118] The established model rats were randomly divided into a model group, a positive control group, Example 1 - 5 groups, and Comparative Example 1 - 7 groups, with 6 rats in each group. The positive control group was intragastrically administered metformin hydrochloride tablets at 250 mg / kg, and the Example and Comparative Example groups were intragastrically administered the corresponding compositions at 8 g (calculated by crude drug amount) / kg, dissolved in distilled water, with a dosing volume of 20 mL / kg. The normal group and the model group were both intragastrically administered an equal volume of distilled water once a day for 6 consecutive weeks.

[0119] After the last administration, the rats in each group were fasted but allowed to drink water for 12 h, anesthetized by intraperitoneal injection of 2% concentration of sodium pentobarbital at 2 mL / kg, blood was collected from the abdominal aorta, and the upper - layer serum was taken after centrifugation. Fasting blood glucose (FBG), blood urea nitrogen (BUN), and serum creatinine (Scr) were detected by enzyme - linked immunosorbent assay.

[0120] The detection results are shown in Table 4.

[0121] Table 4

[0122] Group FBG (mmol / L) BUN (mmol / L) Scr (μmol / L) Normal group 5.14±0.72 6.23±0.64 58.54±3.96 Model group <![CDATA[22.26±1.49 ** > <![CDATA[19.37±2.17 ** > <![CDATA[137.80±9.68 ** > Positive control group <![CDATA[12.75±0.93 ## > <![CDATA[12.85±1.25 ## > <![CDATA[84.72±4.25 ## > Example 1 group <![CDATA[13.54±1.01 ## > <![CDATA[11.88±1.60 ## > <![CDATA[83.25±3.45 ## > Example 2 group <![CDATA[14.30±0.87 ## > <![CDATA[12.44±1.33 ## > <![CDATA[84.07±3.77 ## > Example 3 group <![CDATA[14.46±1.18 ## > <![CDATA[12.69±1.52 ## > <![CDATA[84.19±4.94 ## > Example 4 group <![CDATA[15.11±1.17 ## > <![CDATA[13.27±1.36 ## > <![CDATA[85.56±4.10 ## > Example 5 group <![CDATA[15.18±1.25 ## > <![CDATA[13.32±1.56 ## > <![CDATA[85.83±4.39 ## > Comparative example 1 group <![CDATA[17.29±1.14 #△ > <![CDATA[14.39±1.80 #△ > <![CDATA[109.12±5.33 #△ > Comparative example 2 group <![CDATA[19.21±2.22 #△△ > <![CDATA[16.12±1.55 #△ > <![CDATA[118.48±7.58 #△ > Comparative example 3 group <![CDATA[20.08±2.16 #△△ > <![CDATA[16.61±1.98 #△ > <![CDATA[120.06±6.81 #△ > Comparative example 4 group <![CDATA[18.39±1.53 #△ > <![CDATA[15.59±1.74 #△ > <![CDATA[114.73±6.14 #△ > Comparative example 5 group <![CDATA[17.84±1.23 #△ > <![CDATA[14.76±1.42 #△ > <![CDATA[111.34±5.52 #△ > Comparative example 6 group <![CDATA[18.98±1.75 #△△ > <![CDATA[15.84±1.49 #△ > <![CDATA[116.65±7.06 #△ > Comparative example 7 group <![CDATA[17.55±1.20 #△ > <![CDATA[14.47±1.61 #△ > <![CDATA[110.18±5.37 #△ >

[0123] Note: Compared with the normal group, ** P < 0.01; compared with the model group, # P < 0.05, ## P < 0.01; compared with Example 1 group, △P < 0.05, △△ P < 0.01.

[0124] Results:

[0125] As can be seen from Table 4, after streptozotocin-induced diabetes in rats, the FBG, BUN and Scr of the rats were significantly increased, indicating successful modeling. Compared with the model group, the positive control group, the groups of Examples 1-5 and the groups of Comparative Examples 1-7 could all reduce the FBG, BUN and Scr of the rats to varying degrees. However, compared with the groups of Comparative Examples 1-7, the groups of Examples 1-5 had a better effect on reducing the FBG, BUN and Scr of the rats, and the effect of Example 1 group was the best. The above results show that the products of the embodiments of the present invention can significantly improve diabetic nephropathy in rats.

[0126] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating diabetic nephropathy, characterized in that: The traditional Chinese medicine composition comprises the following components by weight: 250-400 parts of astragalus, 350-500 parts of raw rehmannia, 200-350 parts of bran-fried atractylodes, 50-200 parts of rhubarb, 200-350 parts of motherwort, 200-350 parts of angelica, 200-350 parts of phellodendron, and 30-120 parts of scalded leeches.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition comprises the following components by weight: 300-350 parts of astragalus, 400-450 parts of raw rehmannia, 250-300 parts of bran-fried atractylodes, 100-150 parts of rhubarb, 250-300 parts of motherwort, 250-300 parts of angelica, 250-300 parts of phellodendron, and 50-100 parts of scalded leeches.

3. The Chinese medicine composition according to claim 2, characterized in that: The traditional Chinese medicine composition comprises the following components by weight: 326 parts of astragalus, 435 parts of raw rehmannia, 261 parts of bran-fried atractylodes, 130 parts of rhubarb, 261 parts of motherwort, 261 parts of angelica, 261 parts of phellodendron, and 65 parts of scalded leeches.

4. The method for preparing the Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) extracting the medicinal materials in a prescribed amount with water to obtain an extract; (2) The extract is concentrated under reduced pressure to form a clear paste, and then dried to obtain a Chinese medicine composition.

5. The preparation method according to claim 4, characterized in that: The preparation method comprises the following steps: (1) adding water to the formulated amount of medicinal materials, heating and refluxing for extraction 1-3 times, adding 8-17 times the weight of the medicinal materials of water each time, and extracting for 0.5-1.5 hours each time to obtain an extract; (2) The extract is concentrated under reduced pressure to a clear paste with a relative density of 1.05-1.10, and dried to obtain a Chinese medicine composition.

6. The preparation method according to claim 5, characterized in that: The preparation method comprises the following steps: (1) Add water to the medicinal material in the formula amount, heat and reflux to extract twice, add 14 times the weight of water to the medicinal material for the first time, and extract for 1.5 hours; add 11 times the weight of water to the medicinal material for the second time, and extract for 1.5 hours to obtain an extract; (2) The extract is concentrated under reduced pressure to a clear paste with a relative density of 1.05-1.10, and spray-dried to obtain a Chinese medicine composition.

7. A drug, characterized in that The medicine comprises the Chinese medicine composition according to any one of claims 1 to 3.

8. The drug according to claim 7, characterized in that The medicine is an oral pharmaceutical preparation.

9. The drug according to claim 8, characterized in that The oral pharmaceutical preparation is any one of a decoction, a pill, a tablet, a capsule, a powder, a granule, and an oral liquid.

10. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating diabetic nephropathy.

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