A traditional Chinese medicine composition, preparation, application and preparation method for the combined disease of Shaoyin and Taiyin

Abstract

The present invention relates to the field of traditional Chinese medicine, and specifically provides a traditional Chinese medicine composition, preparation, application and preparation method for the combination of Shaoyin and Taiyin syndromes. The composition consists of the following components: Ephedra, Aconite Root, Poria, Atractylodes Macrocephala, Cassia Twig, Licorice Root, Cuscuta Chinensis, Leech, Earthworm, Mole Cricket, Aspongopus, Mantis Egg-case, Pseudostellaria Heterophylla, and Astragalus Membranaceus. In the present invention, the combination of Mahuang-Fuzi-Gancao Decoction and Linggui Zhugan Decoction warms yang and induces sweating, strengthens the spleen and removes dampness; Astragalus Membranaceus and Pseudostellaria Heterophylla are used in large doses to tonify qi and dredge collaterals; combined with Cuscuta Chinensis and Mantis Egg-case to tonify the kidney and astringe for consolidation; Leech and Earthworm activate blood circulation, eliminate stasis and dredge collaterals; Aspongopus and Mole Cricket regulate qi, dredge collaterals and promote diuresis. The combination of various herbs exerts the effects of supplementing qi, activating blood circulation and promoting diuresis, removing stasis and eliminating masses, dredging collaterals, promoting blood circulation, removing stasis and reuniting collaterals, which can not only enhance the body's immune function, but also solve the hypercoagulable state of the blood in diabetic nephropathy patients, repair and improve the glomerular filtration barrier, so as to achieve the purpose of clearing proteinuria and improving renal function.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition, preparation, application and preparation method for the combined disease of Shaoyin and Taiyin. Background Art

[0002] At present, the prevention and treatment of proteinuria in the medical field are limited. It is mainly hormone combined with immunosuppressants, and has large side effects. Relapse is easy when the dosage is reduced or the drug is stopped. Once a large amount of proteinuria appears, the renal function will deteriorate rapidly, and dialysis or kidney transplantation is required to maintain life, seriously reducing the quality of life of patients and increasing the social and economic burden.

[0003] Diagnostic criteria for nephrotic syndrome: 1. Urinary protein > 3.5 g / d; 2. Plasma albumin < 30 g / L; 3. Edema; elevated blood lipid. Items 1 and 2 are necessary for diagnosis. Membranous nephropathy, diabetic nephropathy, and minimal change nephropathy are common pathological types of nephrotic syndrome. Most cases of minimal change nephropathy are sensitive to hormones and have a good prognosis. 30% of membranous nephropathy will remit spontaneously, and most clinical patients with membranous nephropathy have good efficacy to hormones + immunosuppressants. The prevention and treatment of diabetic nephropathy mainly focus on reducing blood sugar, blood pressure, blood lipid and urinary protein, but there is no safe and effective method to reduce urinary protein in diabetic nephropathy patients. Once the proteinuria in diabetic nephropathy patients is not well controlled, nephrotic syndrome will recur repeatedly, which can cause serious complications such as severe hypoproteinemia, massive edema, heart failure, pleural effusion, thrombosis, and even severe infection. The condition will deteriorate rapidly, and diabetic nephropathy patients will quickly enter the dialysis stage.

[0004] Proteinuria often recurs, or does not disappear for a long time, with a long course of disease, and is difficult to cure. Long-term illness often leads to deficiency, long-term illness often leads to blood stasis, long-term illness enters the collaterals, and long-term illness affects the kidneys. The evil of long-term illness penetrates into the collaterals, blocks qi and blood, and qi and blood are not smooth, kidney collaterals are blocked, and collaterals are stagnant and blocked. It is not possible for general blood-activating drugs to clear them, and inherent collateral evil is easy to enter but difficult to exit. The inventor's team has long-term clinical practice, and insect drugs can often penetrate into the collaterals and unclog the kidney collaterals. Insect drugs are blood and flesh products, sentient beings, and they like to attack and chase, dredge the meridians and collaterals, search and clear, and are everywhere; they are also relatively close to human physique, easy to absorb and use, so most of the drugs are strong and effective, and they play a role in turning the tide, which is incomparable to plants, minerals, etc. Insect drugs, with their peristaltic nature, fly and run, have the power to search and remove blood stasis in the collaterals and to promote the old and bring in the new. In 1997, artificial recombinant hirudin was launched in Germany, but the inhibitory effect of recombinant hirudin on thrombin was 90% lower than that of natural hirudin, and it was easy to cause side effects such as bleeding. Therefore, my country banned the import of recombinant hirudin. Modern medical research results show that hirudin is the strongest, most effective and safest natural thrombin specific inhibitor found in the world so far. The record of earthworms in "Compendium of Materia Medica" is: earthworms are cold and descend, so they can relieve various fevers, and descend so they can promote urination, control foot diseases and open up the meridians. "Huangdi Neijing" records that earthworms "are salty, cold, and cool, and are good at running around." Chinese medicine classics say "earthworms are impenetrable to heaven and earth, and are the best at activating blood circulation." Modern research has found that earthworm protein contains a variety of enzymes, nucleic acids, trace elements and other components, which can improve immunity and dissolve blood clots, and thrombolysis does not affect the body's coagulation mechanism and does not cause bleeding side effects.

[0005] At present, Western medicine has no specific treatment for proteinuria in chronic nephritis and nephrotic syndrome. Research mainly focuses on reducing urine protein and blood pressure control. The measures to control proteinuria are mainly ACEI and ARB drugs, which have problems such as insensitivity in some patients and side effects caused by long-term use. The Chinese patent medicines for reducing proteinuria on the market currently include Bailing Capsules, Zhilingjunsu (the main ingredient is artificially cultivated Cordyceps sinensis), Huangkui Capsules (the main ingredient is Hibiscus hibiscus flower), etc. The components of these Chinese patent medicines are relatively simple and often fail to take into account complex and difficult-to-treat proteinuria. At the same time, it mainly targets the above symptoms from the perspective of tonifying the kidney and dispelling wind.

[0006] The present invention improves symptoms from the perspective of Taiyin and Shaoyin combined diseases based on the principle of monarch, minister, assistant and envoy. Summary of the invention

[0007] The object of the present invention is to provide a traditional Chinese medicine composition for Shaoyin and Taiyin combined diseases, wherein the composition is composed of the following components: ephedra, aconite, poria, atractylodes, cinnamon twig, liquorice, dodder seed, leech, earthworm, mole cricket, nine-scented insect, mulberry silkworm, pseudostellaria, and astragalus.

[0008] As an embodiment of the present invention, calculated by weight parts, the composition is composed of the following components: 3 - 15 parts of Ephedrae Herba, 3 - 15 parts of Aconiti Lateralis Radix Praeparata, 9 - 30 parts of Poria, 9 - 30 parts of Cinnamomi Ramulus, 9 - 30 parts of Atractylodis Macrocephalae Rhizoma, 9 - 30 parts of Glycyrrhizae Radix et Rhizoma, 12 - 30 parts of Cuscuta Chinensis Lam., 3 - 12 parts of Hirudo, 6 - 12 parts of Pheretima, 3 - 9 parts of Gryllotalpa africana Palisot de Beauvois, 3 - 15 parts of Aspongopus chinensis Dallas, 6 - 18 parts of Ootheca Mantidis, 15 - 30 parts of Pseudostellariae Radix, 15 - 45 parts of Astragali Radix.

[0009] As an embodiment of the present invention, calculated by weight parts, the composition is composed of the following components: 6 parts of Ephedrae Herba, 6 parts of Aconiti Lateralis Radix Praeparata, 12 parts of Poria, 6 parts of Atractylodis Macrocephalae Rhizoma, 9 parts of Cinnamomi Ramulus, 6 parts of Glycyrrhizae Radix et Rhizoma, 6 parts of Cuscuta Chinensis Lam., 6 parts of Hirudo, 6 parts of Pheretima, 6 parts of Gryllotalpa africana Palisot de Beauvois, 6 parts of Aspongopus chinensis Dallas, 15 parts of Ootheca Mantidis, 30 parts of Pseudostellariae Radix, 45 parts of Astragali Radix.

[0010] The second aspect of the present invention provides the application of the traditional Chinese medicine composition for treating the combination of Shaoyin and Taiyin syndromes in the preparation of drugs for treating diabetic nephropathy.

[0011] The third aspect of the present invention provides that the traditional Chinese medicine composition for treating the combination of Shaoyin and Taiyin syndromes is used for preventing, alleviating or treating edema.

[0012] The fourth aspect of the present invention provides a pharmaceutical preparation, which includes the above - mentioned traditional Chinese medicine composition and / or pharmaceutically acceptable excipients.

[0013] As an embodiment of the present invention, the dosage form of the pharmaceutical preparation is selected from tablets, granules, capsules, powders or solutions.

[0014] The fifth aspect of the present invention provides a preparation method of the pharmaceutical preparation, and the steps of the preparation method are as follows:

[0015] S01 Classify the components of the traditional Chinese medicine composition;

[0016] S02 Extract the components of the traditional Chinese medicine composition classified in step S01;

[0017] S03 Make the components extracted in step S02 into a pharmaceutical preparation.

[0018] As an embodiment of the present invention, in step S01, the classification is as follows:

[0019] Group A: Ephedrae Herba, Poria, Glycyrrhizae Radix et Rhizoma, Cuscuta Chinensis Lam., Pseudostellariae Radix, Astragali Radix;

[0020] Group B: Atractylodis Macrocephalae Rhizoma, Cinnamomi Ramulus;

[0021] Group C: Hirudo, Pheretima, Gryllotalpa africana Palisot de Beauvois, Aspongopus chinensis Dallas;

[0022] Group D: Ootheca Mantidis, Aconiti Lateralis Radix Praeparata.

[0023] As an implementation manner of the present invention, the specific steps of step S02 are as follows: Groups A to E respectively perform extraction of active ingredients, and then mix them.

[0024] Adopting the above technical solution, the present invention has the following beneficial effects:

[0025] In the present invention, Mahuang Fuzi Gancao Decoction combined with Linggui Zhugan Decoction warm yang and induce sweating, strengthen the spleen and remove dampness; Astragalus membranaceus and Pseudostellaria heterophylla are used in large doses to tonify qi and dredge collaterals; combined with Cuscuta chinensis and Mantis egg-case to tonify the kidney and astringe and consolidate; Hirudo and Pheretima to activate blood circulation, remove stasis and dredge collaterals; Aspongopus and Gryllotalpa africana to regulate qi, dredge collaterals and promote diuresis. The combination of various herbs exerts the effects of supplementing qi, activating blood circulation and promoting diuresis, removing stasis and dredging collaterals, promoting smooth blood circulation, removing stasis and reuniting collaterals, which can not only increase the body's immune function, but also solve the hypercoagulable state of the blood of diabetic nephropathy patients, repair and improve the glomerular filtration barrier, so as to achieve the purpose of clearing proteinuria and improving renal function. Description of the Drawings

[0026] In order to more clearly illustrate the specific implementation manners of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific implementation manners or the prior art. Obviously, the drawings in the following description are some implementation manners of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0027] Figure 1 Effect of HE staining on the renal tissue morphology of normal group rats under light microscopy;

[0028] Figure 2 Effect of HE staining on the renal tissue morphology of model group rats under light microscopy;

[0029] Figure 3 Effect of HE staining on the renal tissue morphology of basic group rats under light microscopy;

[0030] Figure 4 Effect of HE staining on the renal tissue morphology of invention group rats under light microscopy;

[0031] Figure 5 Effect of Masson staining on the renal tissue morphology of normal group rats under light microscopy;

[0032] Figure 6 Effect of Masson staining on the renal tissue morphology of model group rats under light microscopy;

[0033] Figure 7 Effect of Masson staining on the renal tissue morphology of basic group rats under light microscopy;

[0034] Figure 8 Effect of Masson staining on the renal tissue morphology of invention group rats under light microscopy;

[0035] Figure 9 Effect on the ultrastructural changes of the kidneys of rats in the normal group under electron microscopy;

[0036] Figure 10 Effect on the ultrastructural changes of the kidneys of rats in the model group under electron microscopy;

[0037] Figure 11 Effect on the ultrastructural changes of the kidneys of rats in the basic group under electron microscopy;

[0038] Figure 12 Effect on the ultrastructural changes of the kidneys of rats in the invention group under electron microscopy. Detailed implementation manners

[0039] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0040] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating the combination of Shaoyin and Taiyin syndromes. The composition is composed of the following components: Ephedra, Aconite, Poria, Atractylodes Macrocephala, Cinnamon Twig, Licorice, Cuscuta Chinensis, Leech, Earthworm, Mole Cricket, Aspongopus, Mantis Egg-case, Pseudostellaria Heterophylla, Astragalus Membranaceus.

[0041] As an implementation manner of the present invention, by weight, the composition is composed of the following components: Ephedra 3 - 15, Aconite 3 - 15, Poria 9 - 30, Cinnamon Twig 9 - 30, Atractylodes Macrocephala 9 - 30, Licorice 9 - 30, Cuscuta Chinensis 12 - 30, Leech 3 - 12, Earthworm 6 - 12, Mole Cricket 3 - 9 g, Aspongopus 3 - 15, Mantis Egg-case 6 - 18, Pseudostellaria Heterophylla 15 - 30, Astragalus Membranaceus 15 - 45.

[0042] As an implementation manner of the present invention, by weight, the composition is composed of the following components: Ephedra 6, Aconite 6, Poria 12, Atractylodes Macrocephala 6, Cinnamon Twig 9, Licorice 6, Cuscuta Chinensis 6, Leech 6, Earthworm 6, Mole Cricket 6, Aspongopus 6, Mantis Egg-case 15, Pseudostellaria Heterophylla 30, Astragalus Membranaceus 45.

[0043] In the present invention, Ephedra is warm in nature, pungent and slightly bitter in taste, and belongs to the lung and bladder meridians; it induces sweating and relieves exterior syndrome, disperses lung qi and relieves asthma, promotes diuresis and reduces edema, and is used for wind-cold cold, cough and asthma, and wind-water edema.

[0044] Aconite is extremely hot in nature, pungent and sweet in taste, and belongs to the heart, kidney and spleen meridians; it restores yang and rescues from collapse, supplements fire and assists yang, dispels cold and relieves pain, and is used for yang collapse syndrome, yang deficiency syndrome, and cold arthralgia syndrome.

[0045] Poria cocos has a neutral nature; tastes sweet and bland; acts on the heart, spleen, and kidney meridians; promotes diuresis to alleviate edema, percolates dampness, strengthens the spleen, and calms the heart, and is used for edema, phlegm retention, diarrhea due to spleen deficiency, palpitation, and insomnia.

[0046] Cinnamomum cassia has a warm nature; tastes pungent and sweet; acts on the heart, lung, and bladder meridians; induces sweating to relieve the exterior syndrome, warms and unblocks the meridians, promotes yang qi transformation, and is used for wind-cold common cold, various pain syndromes due to cold congealing and blood stasis, phlegm retention, fluid retention syndrome, and palpitation.

[0047] Atractylodes macrocephala has a warm nature; tastes sweet and bitter; acts on the spleen and stomach meridians; strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and prevents miscarriage, and is used for spleen qi deficiency syndrome, spontaneous sweating due to qi deficiency, and restlessness of the fetus due to spleen deficiency.

[0048] Glycyrrhiza uralensis has a neutral nature; tastes sweet; invigorates the spleen and replenishes qi, resolves phlegm and stops coughing, alleviates spasm and pain, clears heat and detoxifies, and harmonizes various medicinal herbs, and is used for insufficiency of heart qi, intermittent pulse, palpitation, spleen qi deficiency syndrome, cough and asthma, spasmodic pain in the abdomen and extremities, pyogenic infections, sore throat, food and drug poisoning, and harmonizing the properties of medicinal herbs.

[0049] Cuscuta chinensis has a neutral nature; tastes pungent and sweet; acts on the kidney, liver, and spleen meridians; tonifies the kidney and replenishes essence, nourishes the liver and improves eyesight, stops diarrhea, and prevents miscarriage, and is used for soreness and weakness of the waist due to kidney deficiency, impotence and spermatorrhea, frequent urination, infertility due to cold in the uterus, deficiency of the liver and kidney, dim eyesight, diarrhea due to deficiency of the spleen and kidney yang, and restlessness of the fetus due to kidney deficiency.

[0050] Whitmania pigra has a neutral nature; tastes salty and bitter; is slightly poisonous; acts on the liver meridian; breaks blood to unblock the meridians, removes stasis and dissipates masses, and is used for amenorrhea due to blood stasis, mass accumulation, traumatic injury, and pain in the chest and abdomen.

[0051] Pheretima aspergillum has a cold nature; tastes salty; acts on the liver, spleen, and bladder meridians; clears heat and extinguishes wind, dredges the meridians, relieves asthma, and promotes diuresis, and is used for high fever with convulsions, mania, qi stagnation and blood stasis, hemiplegia, arthralgia syndrome, asthma due to lung heat, dysuria, and urinary retention.

[0052] Gryllotalpa africana has a cold nature; tastes salty; acts on the bladder, large intestine, and small intestine meridians; promotes diuresis to alleviate edema, and promotes urination, and is used for edema syndrome and stranguria syndrome.

[0053] Coridius chinensis has a warm nature; tastes salty; acts on the liver, spleen, and kidney meridians; regulates qi to relieve pain, warms the kidney and boosts yang, and is used for pain in the chest, hypochondrium, and abdomen, impotence, soreness and cold pain in the waist and knees, and frequent urination.

[0054] Mantidis ootheca has a neutral nature; tastes sweet and salty; acts on the liver and kidney meridians; astringes essence and reduces urination, tonifies the kidney and boosts yang, and is used for spermatorrhea and emission, enuresis and frequent urination, leukorrhagia, and impotence due to kidney deficiency.

[0055] Pseudostellaria heterophylla, with its Latin name Radix Pseudoxtellariae, has a neutral nature; tastes sweet and slightly bitter; acts on the spleen and lung meridians; supplements qi and strengthens the spleen, promotes the production of body fluid and moistens the lungs, and is used for deficiency syndrome of both qi and yin of the spleen and lung.

[0056] Astragalus membranaceus, with its Latin name being Astragali Radix, is slightly warm in nature, sweet in taste, attributing to the spleen and lung meridians, strengthening the spleen and replenishing the middle, lifting yang and raising prolapse, benefiting qi and consolidating the exterior, inducing diuresis, expelling toxins and promoting granulation, treating chronic diarrhea with rectal prolapse, visceral ptosis, qi-deficiency edema, chronic cough due to lung deficiency, shortness of breath and fatigue, spontaneous sweating due to exterior deficiency, qi and blood deficiency, difficult ulceration and necrosis of sores and ulcers, and difficult healing after long-term ulceration, qi-deficiency and blood stasis.

[0057] In this invention, Ephedra, Aconiti Lateralis Radix Praeparata, Astragalus membranaceus, and Pseudostellaria heterophylla are used as the monarch drugs to tonify the kidney, strengthen the spleen and promote diuresis, Poria, Cinnamomi Ramulus, Atractylodis Macrocephalae Rhizoma, Cuscuta chinensis, and Mantis Egg-case are used as the minister drugs, focusing on strengthening the spleen, promoting diuresis and astringing essence; Hirudo, Pheretima, Gryllotalpa africana, Aspongopus chinensis, and Asarum are used as the assistant drugs, functioning in activating blood circulation and promoting diuresis, and Glycyrrhiza uralensis is used as the envoy drug, focusing on regulating and moderating the drastic properties.

[0058] The second aspect of this invention provides the application of the described traditional Chinese medicine composition for treating the combination of Shaoyin and Taiyin syndromes in the preparation of drugs for treating diabetic nephropathy.

[0059] The third aspect of this invention provides the described traditional Chinese medicine composition for treating the combination of Shaoyin and Taiyin syndromes for preventing, alleviating or treating edema.

[0060] The fourth aspect of this invention provides a pharmaceutical preparation, which includes the described traditional Chinese medicine composition and / or pharmaceutically acceptable excipients.

[0061] As an embodiment of this invention, the dosage form of the pharmaceutical preparation is selected from tablets, granules, capsules, powders or solutions.

[0062] The composition described in this invention can be administered through various routes, such as oral tablets, capsules, powders, oral liquids, injections and transdermal preparations. According to conventional pharmaceutical practices, pharmaceutically acceptable carriers include diluents, fillers, disintegrants, wetting agents, lubricants, coloring agents, flavoring agents or other conventional additives. Typical pharmaceutically acceptable carriers include, for example, microcrystalline cellulose, starch, cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, maltitol, citric acid, sodium dodecyl sulfate or magnesium stearate, etc.

[0063] The fifth aspect of this invention provides a preparation method of the pharmaceutical preparation, and the steps of the preparation method are as follows:

[0064] S01 Classify the components of the traditional Chinese medicine composition;

[0065] S02 Extract the components of the traditional Chinese medicine composition classified in step S01;

[0066] S03 Make the components extracted in step S02 into a pharmaceutical preparation.

[0067] As an embodiment of this invention, in step S01, the classification is as follows:

[0068] Group A: Ephedra, Poria, Glycyrrhiza uralensis, Cuscuta chinensis, Pseudostellaria heterophylla, Astragalus membranaceus;

[0069] Group B: Atractylodes macrocephala Koidz. and Cinnamomum cassia Presl

[0070] Group C: Hirudo, Pheretima aspergillum (E. Perrier), Gryllotalpa africana Palisot de Beauvois, and Aspongopus chinensis Dallas

[0071] Group D: Ootheca Mantidis and Aconitum carmichaelii Debx.

[0072] As an embodiment of the present invention, the specific steps of step S02 are as follows: The active ingredients of groups A to E are extracted respectively, and then mixed.

[0073] Preferably, the extraction method of group A is as follows

[0074] Mix Ephedra sinica Stapf, Poria cocos (Schw.) Wolf, Glycyrrhiza uralensis Fisch., Cuscuta chinensis Lam., Pseudostellaria heterophylla (Miq.) Pax ex Pax & Hoffm., and Astragalus membranaceus (Fisch.) Bunge, soak the medicine in water for 50 minutes, decoct with 2 - 4 times the volume of water for 60 minutes each time, for 3 consecutive times, and keep the liquid and remove the residue

[0075] The extraction method of group B is as follows

[0076] Preheat the pot to 280 °C, sprinkle 10 g of honey - fried wheat bran into the pot, add Atractylodes macrocephala Koidz. slices and Cinnamomum cassia Presl when smoking, stir - fry for 12 min until the burnt aroma escapes, take out, sieve out the honey - fried wheat bran, and grind the Atractylodes macrocephala Koidz. slices and cinnamon while they are hot through a 40 - mesh sieve; then carry out extraction under the conditions of extraction temperature 35 °C, extraction time 80 min, CO 2 flow rate 20 kg / h, and extraction pressure 18 MPa to obtain the extract of group B; (Take 100 g of wheat bran, add 30 g of honey and 50 g of clear water, stir - fry at 90 °C for 90 s to obtain honey - fried wheat bran).

[0077] The extraction method of group C is as follows: Mix the components of group C, spray evenly with white liquor (100 parts by mass of liquor∶15 parts by mass of component C), moisten for 1 h. Separately, place the honey - fried wheat bran in the pot and stir - fry until slightly smoking, then put group C into the pot and stir - fry together. Keep stirring for 15 s and then quickly pour it into a container, cover it and let it stand for 5 - 10 min, sieve out the wheat bran, let it cool, grind and crush it, and then carry out cold - soaking extraction with 5 times the volume of 60% ethanol at room temperature for 3 times, 24 hours each time, and combine the extraction liquids

[0078] The extraction method of group D is as follows: Take Ootheca Mantidis, add 50 mL of brine (the ratio of medicinal material to salt is 100:2), stir - fry at 110 °C for 10 min to obtain salt - processed Ootheca Mantidis. Take the dry powder of salt - processed Ootheca Mantidis and the powder of Aconitum carmichaelii Debx., with the solid - liquid ratio of 1:20 g / mL, carry out ultrasonic extraction with 70% ethanol (120 W, frequency 40 kHz) for 1 h, repeat 3 times, and combine the extraction liquids

[0079] The extracts prepared from the above-mentioned groups A, C, and D are mixed, and then concentrated to a clear paste with a relative density of 1.32-1.38, and then the extract of component B is added, stirred and mixed, and then concentrated to a clear paste with a relative density of 1.32-1.38; vacuum drying, crushing, sieving, mixing, preparing into an oral dosage form, and sterilizing with Co60.

[0080] TCM classics have their unique advantages and characteristics in the diagnosis and treatment of CKD, and the effect of using classic prescriptions in clinical practice is particularly prominent. TCM believes that proteinuria belongs to the category of "edema". In recent years, TCM treatment of proteinuria has also been studied in depth. Based on previous research, the inventor team has obtained the following experience in the diagnosis and treatment of edema in TCM. "Jingyue Complete Book" says: "All edema and other symptoms are related diseases of the lungs, spleen, and kidneys. Water is the most yin, and its root is in the kidney; water is transformed into qi, so its symptoms are in the lungs; water is afraid of soil, so its control is in the spleen. Now if the lungs are weak, the qi will not transform into fluid but into water, if the spleen is weak, the soil will not control water but will overcome it, and if the kidneys are weak, the water will have no master and will run wildly." Taking the kidney as the root, the lung as the symptom, and the spleen as the control is the key to the pathogenesis of edema. Edema is mostly yin syndrome, mainly Shaoyin and Taiyin combined disease.

[0081] The best compatibility scheme of ephedra, aconite and liquorice in the present invention has the highest safety and is a warming yang and releasing agent. This prescription is very effective in treating edema caused by acute and chronic nephritis and heart disease. There is an anticoagulant substance in the saliva of leeches, called hirudin, which is a polypeptide of 65 amino acids. Reusing hirudin can reduce the deposition of fibrinogen-related antigens in the glomerulus, reduce the proliferation of glomerular mesangial cells and glomerular sclerosis, reduce proteinuria and hypoproteinemia, and improve renal function. Earthworm can enhance immunity, and earthworm liquid can reduce exudation, shorten the inflammatory cycle, and accelerate wound healing. Mole crickets contain 13 kinds of amino acids, which have the effects of diuresis, detumescence, stone removal, and anti-tumor. Astragalus is one of the commonly used traditional Chinese medicines for reducing proteinuria caused by various kidney diseases. Patients with renal proteinuria often have selenium deficiency, and selenium has the function of protecting the body from immune oxidative damage and can enhance the antioxidant effect of certain free radical scavengers. Therefore, it may protect the charge barrier and mechanical barrier of the glomerular basement membrane through the above-mentioned effects to reduce proteinuria. Astragalus also has a regulatory function on T lymphocytes.

[0082] The present invention combines Mahuangfuzigancao decoction with Lingguishugan decoction to warm yang and release the exterior, invigorate the spleen and remove dampness; heavily uses Astragalus and Radix Pseudostellariae to invigorate qi and dredge collaterals; combines Cuscuta and Silkworm to invigorate the kidney and astringe; Leech and earthworm invigorate blood circulation, eliminate symptoms and dredge collaterals; Nine-scented insect and mole cricket regulate qi, dredge collaterals and promote diuresis. The combination of all the medicines can play the effects of invigorating qi, invigorating blood circulation and promoting diuresis, removing blood stasis, eliminating symptoms and dredge collaterals, promoting blood circulation, removing blood stasis and complexing, which can not only increase the body's immune function, but also solve the hypercoagulable state of blood in patients with diabetic nephropathy, repair and improve the filtration barrier of glomeruli, thereby achieving the purpose of removing proteinuria and improving renal function.

[0083] Meanwhile, according to the characteristics of the components, the present invention has specifically set the preparation method, giving full play to the advantages of each component and avoiding the disadvantages, thus achieving the maximum medicinal effect.

[0084] The following further explains and illustrates the present invention in combination with specific embodiments.

[0085] Example 1

[0086] This example provides a traditional Chinese medicine preparation, which is composed of the following components: Ephedra 6, Aconite 6, Poria 12, Atractylodes Macrocephala 6, Cinnamon Twig 9, Licorice 6, Cuscuta 6, Leech 6, Earthworm 6, Mole Cricket 6, Aspongopus 6, Mantis Egg-case 15, Pseudostellaria Heterophylla 30, Astragalus Membranaceus 45; and the grouping is as follows:

[0087] Group A: Ephedra, Poria, Licorice, Cuscuta, Pseudostellaria Heterophylla, Astragalus Membranaceus;

[0088] Group B: Atractylodes Macrocephala, Cinnamon Twig;

[0089] Group C: Leech, Earthworm, Mole Cricket, Aspongopus;

[0090] Group D: Mantis Egg-case, Aconite.

[0091] The preparation method is as follows:

[0092] (1) The extraction method of Group A is as follows:

[0093] Mix Ephedra, Poria, Licorice, Cuscuta, Pseudostellaria Heterophylla, and Astragalus Membranaceus, soak the medicine in water for 50 minutes, decoct with 2 - 4 times the volume of water for 60 minutes each time, for 3 consecutive times, and keep the liquid and remove the residue.

[0094] The extraction method of Group B is as follows: Preheat the pot to 280 °C, sprinkle 10 g of honey - roasted wheat bran into the pot, when it starts to smoke, add Atractylodes Macrocephala slices and Cinnamon Twig, stir - fry for 12 min until the burnt aroma escapes, take out, sieve off the honey - roasted wheat bran, and grind the Atractylodes Macrocephala slices and Cinnamon Twig while they are still hot through a 40 - mesh sieve; then carry out extraction under the conditions of extraction temperature 35 °C, extraction time 80 min, CO 2 flow rate 20 kg / h, and extraction pressure 18 MPa to obtain the extract of Group B; (Take 100 g of wheat bran, add 30 g of honey and 50 g of clear water, stir - fry at 90 °C for 90 s to obtain honey - roasted wheat bran).

[0095] The extraction method of Group C is as follows: Mix the components of Group C, spray evenly with white liquor (100 parts by mass of liquor ∶ 15 parts by mass of component C), moisten for 1 h. Separately, place the honey - roasted wheat bran in the pot and stir - fry until it starts to smoke slightly, then put in Group C and stir - fry together. Keep stirring for 15 s and then quickly pour it into a container, cover it and let it stand for 5 - 10 min, sieve off the wheat bran, let it cool, grind and crush it, and then carry out cold extraction with 5 times the volume of 60% ethanol at room temperature for 3 times, 24 hours each time, and combine the extraction liquids.

[0096] The extraction method of Group D is as follows: Take sangpiaoxiao, add 50 mL of brine (the ratio of medicinal materials to salt is 100:2), stir-fry at 110 °C for 10 min to obtain salt-processed sangpiaoxiao. Take the dry powder of salt-processed sangpiaoxiao and the powder of aconite root, with the solid-liquid ratio of 1:20 g / mL, extract with 70% ethanol by ultrasonic wave (120 W, frequency 40 kHz) for 1 h, repeat 3 times, and combine the extracts.

[0097] (2) Mix the extracts prepared from the above-mentioned Groups A, C, and D, then concentrate to a clear paste with a relative density of 1.32 - 1.38, add the extract of Component B, stir and mix, and then concentrate to a clear paste with a relative density of 1.32 - 1.38 again; dry under reduced pressure, pulverize, sieve, mix evenly, prepare into an oral dosage form, and sterilize with Co60.

[0098] Example 2

[0099] This example provides a traditional Chinese medicine preparation, which is composed of the following components: 6 parts of ephedra, 6 parts of aconite root, 12 parts of poria, 6 parts of atractylodes macrocephala, 9 parts of cassia twig, 6 parts of licorice, 6 parts of dodder seed, 6 parts of leech, 6 parts of earthworm, 6 parts of mole cricket, 6 parts of stinky bug, 15 parts of sangpiaoxiao, 30 parts of pseudostellaria root, 45 parts of astragalus membranaceus; and the grouping is as follows:

[0100] The preparation method is as follows:

[0101] (1) After weighing and mixing the above components, soak the medicine in water for 50 minutes, decoct with 2 - 4 times the volume of water each time for 60 minutes, continuously for 3 times, keep the liquid and remove the residue; concentrate the extract to a clear paste with a relative density of 1.32 - 1.38; dry under reduced pressure, pulverize, sieve, mix evenly, prepare into an oral dosage form, and sterilize with Co60.

[0102] Example 3

[0103] This example provides a traditional Chinese medicine preparation, which is composed of the following components: 6 parts of ephedra, 6 parts of aconite root, 12 parts of poria, 5 parts of atractylodes macrocephala, 9 parts of cassia twig, 6 parts of licorice, 5 parts of dodder seed, 7 parts of leech, 6 parts of earthworm, 10 parts of mole cricket, 6 parts of stinky bug, 15 parts of sangpiaoxiao, 45 parts of pseudostellaria root, 45 parts of astragalus membranaceus; and the grouping is as follows:

[0104] Group A: ephedra, poria, licorice, dodder seed, pseudostellaria root, astragalus membranaceus;

[0105] Group B: atractylodes macrocephala, cassia twig;

[0106] Group C: leech, earthworm, mole cricket, stinky bug;

[0107] Group D: sangpiaoxiao, aconite root.

[0108] The preparation method is as follows:

[0109] (1) The extraction method of Group A is as follows:

[0110] After mixing Ephedrae Herba, Poria, Glycyrrhizae Radix, Cuscuta Chinensis Lam., Pseudostellariae Radix, and Astragali Radix, soak the medicinal materials in water for 50 minutes, decoct with 2 - 4 times the volume of water for 60 minutes each time, do this continuously for 3 times, keep the liquid and discard the residue.

[0111] The extraction method of Group B is as follows: When preheating the pot to 280 °C, sprinkle 10 g of honey-fried wheat bran into the pot. When it starts to smoke, add Atractylodis Macrocephalae Rhizoma slices and Cinnamomi Ramulus, stir-fry for 12 min until the burnt aroma escapes, take out, sieve off the honey-fried wheat bran, and grind the Atractylodis Macrocephalae Rhizoma slices and Cinnamomi Ramulus while they are hot through a 40-mesh sieve; then carry out extraction under the conditions of an extraction temperature of 35 °C, an extraction time of 80 min, a CO 2 flow rate of 20 kg / h, and an extraction pressure of 18 MPa to obtain the extract of Group B; (Take 100 g of wheat bran, add 30 g of honey and 50 g of clear water, stir-fry at 90 °C for 90 s to obtain honey-fried wheat bran).

[0112] The extraction method of Group C is as follows: Mix the components of Group C, spray evenly with white liquor (100 parts by mass of liquor ∶ 15 parts by mass of Component C), moisten for 1 h. Separately, place the honeyed wheat bran in the pot and stir-fry until slightly smoking, then put in Group C and stir-fry together. After continuously stirring for 15 s, quickly pour it into a container, cover it, and let it stand for 5 - 10 min. Sieve off the wheat bran, let it cool, grind and crush it, and then carry out cold extraction with 5 times the volume of 60% ethanol at room temperature for 3 times, 24 hours each time, and combine the extraction liquids.

[0113] The extraction method of Group D is as follows: Take Ootheca Mantidis, add 50 mL of brine (the ratio of medicinal material to table salt is 100:2), stir-fry at 110 °C for 10 min to obtain salted Ootheca Mantidis. Take the dry powder of salted Ootheca Mantidis and the powder of Aconiti Lateralis Radix Preparata, with a material-liquid ratio of 1:20 g / mL, and carry out ultrasonic extraction with 70% ethanol (120 W, frequency 40 kHz) for 1 h, repeat 3 times, and combine the extraction liquids.

[0114] (2) Mix the extraction liquids prepared from the above-mentioned Groups A, C, and D, then concentrate to a clear paste with a relative density of 1.32 - 1.38, then add the extract of Component B, stir and mix, and then concentrate again to a clear paste with a relative density of 1.32 - 1.38; carry out vacuum drying, pulverize, sieve, mix evenly, prepare an oral dosage form, and sterilize with Co60.

[0115] Example 4

[0116] This example provides a traditional Chinese medicine preparation, which is composed of the following components: 6 parts of Ephedrae Herba, 6 parts of Aconiti Lateralis Radix Preparata, 12 parts of Poria, 6 parts of Atractylodis Macrocephalae Rhizoma, 9 parts of Cinnamomi Ramulus, 6 parts of Glycyrrhizae Radix, 6 parts of Cuscuta Chinensis Lam., 6 parts of Whitmania Pigra Whitman, 6 parts of Pheretima Aspera, 6 parts of Gryllotalpa africana Palisot de Beauvois, 6 parts of Coridius chinensis Dallas, 15 parts of Ootheca Mantidis, 30 parts of Pseudostellariae Radix, 45 parts of Astragali Radix; and the grouping is as follows:

[0117] Group A: Ephedrae Herba, Poria, Glycyrrhizae Radix, Cuscuta Chinensis Lam., Pseudostellariae Radix, Astragali Radix;

[0118] Group B: Atractylodis Macrocephalae Rhizoma, Cinnamomi Ramulus;

[0119] Group C: Hirudo, Pheretima aspergillum, Gryllotalpa africana, Coridius chinensis;

[0120] Group D: Ootheca Mantidis, Aconiti Lateralis Radix Praeparata.

[0121] The preparation method is as follows:

[0122] (1) The extraction method of the said Group A is as follows:

[0123] Mix Ephedrae Herba, Poria, Glycyrrhizae Radix, Cuscuta chinensis, Pseudostellaria heterophylla, and Astragali Radix, soak the drugs in water for 50 minutes, decoct with 2 - 4 times the volume of water for 60 minutes each time, for 3 consecutive times, leave the liquid and remove the residues.

[0124] The extraction method of Group B is as follows: Preheat the pot to 280 °C, sprinkle 10 g of honey - fried wheat bran into the pot, when it starts to smoke, add Atractylodis Macrocephalae Rhizoma Slices and Ramulus Cinnamomi, stir - fry for 12 min until the burnt aroma escapes, take out, sieve out the honey - fried wheat bran, and grind the Atractylodis Macrocephalae Rhizoma Slices and Cinnamomi Cortex while they are hot through a 40 - mesh sieve; then carry out extraction under the conditions of extraction temperature 35 °C, extraction time 80 min, CO 2 flow rate 20 kg / h, and extraction pressure 18 MPa to obtain the extract of Group B; (Take 100 g of wheat bran, add 30 g of honey and 50 g of clear water, stir - fry at 90 °C for 90 s to obtain honey - fried wheat bran).

[0125] The extraction methods of Group C and Group D are as follows: Mix the components of Group C and Group D, spray evenly with white liquor (100 parts by mass of liquor ∶ 15 parts by mass of Component C), moisten for 1 h. Separately, place the honey - fried wheat bran in the pot and stir - fry until it starts to smoke slightly, then put in Group C and Group D and stir - fry together. Keep stirring for 15 s and then quickly pour into a container, cover with a lid and simmer for 5 - 10 min, sieve out the wheat bran, let it cool, grind and crush, then carry out cold - soaking extraction with 5 times the volume of 60% ethanol at room temperature for 3 times, 24 hours each time, and combine the extraction liquids.

[0126] (2) Mix the extraction liquids prepared from the above - mentioned Group A, Group B, Group C, and Group D, then concentrate to a clear paste with a relative density of 1.32 - 1.38, carry out vacuum drying, pulverize, sieve, mix evenly, prepare into an oral dosage form, and sterilize with Co60.

[0127] The effects of the present invention are illustrated by the following animal experiments. In the experiments, the traditional Chinese medicine preparation of the invention group is the traditional Chinese medicine preparation described in Examples 1 - 4, and the control drug is Mahuang - Fuzi - Gancao Decoction combined with Linggui - Zhugan Decoction plus Cuscuta chinensis and Hirudo provided by Jiangyin Tianjiang Pharmaceutical Co., Ltd. (basic group).

[0128] The effects of the present invention are illustrated by animal experiments. Test rats: SD, SPF - grade, male, body weight (130 ± 10) g, provided by Bikai, license number: SCXK (Shanghai) 2013 - 0016, control drug: Mahuang - Fuzi - Gancao Decoction combined with Linggui - Zhugan Decoction plus Cuscuta chinensis and Hirudo provided by Jiangyin Tianjiang Pharmaceutical Co., Ltd.

[0129] Experimental reagents: Streptozotocin (STZ): Manufacturer Sigma, batch number S0130;

[0130] Hematuria biochemical reagents: Shanghai Fosun Changzheng Medical Co., Ltd.;

[0131] WT-1 antibody: Manufacturer Abcam, batch number ab89901;

[0132] Hematoxylin-eosin staining solution: Nanjing Jiancheng;

[0133] Masson staining kit: Beyotime.

[0134] Experimental instruments: Dehydrator: Wuhan Junjie Electronics Co., Ltd., JJ-12J;

[0135] Pathological slicer: Shanghai Leica Instruments Co., Ltd., RM2016;

[0136] Light microscope: Nikon, Japan, NIKON ECLIPSE CI;

[0137] Imaging system: Nikon, Japan, NIKON DS-U3;

[0138] Blood glucose meter: OneTouch Ultra, Johnson & Johnson.

[0139] Experimental methods:

[0140] First step, establishment of diabetic nephropathy animal model: SD rats were adaptively fed for one week. After 8 hours of fasting with free access to water, the rats were anesthetized by intraperitoneal injection of 1.5% sodium pentobarbital at a dose of 30 mg / kg. The rats were fixed on the operating board, and left nephrectomy was performed. After 1 week of adaptive feeding, the rats were fasted for 12 hours with free access to water, and then injected intraperitoneally with 60 mg / kg STZ. Successful diabetes modeling was defined as two random blood glucose levels greater than 16.7 mmol / L within 72 hours after surgery. Four weeks after successful diabetes modeling, the urine of the rats was collected, and the urine protein of the rats was detected. The kidneys of the rats were collected, and the renal tissues were fixed, sectioned, and stained to observe the pathological changes of the rats.

[0141] Second step: Animal grouping and drug administration

[0142] SD rats were selected and divided into normal group, model group, basic group, and invention group. Except for the blank group and the model group which were gavaged with distilled water, the basic group and the invention group were given corresponding drugs once a day for 4 consecutive weeks of gavage. The gavage drug dose was calculated according to the animal and human drug conversion table.

[0143] Third step: Index detection:

[0144] Urinary protein detection: Before and after drug administration and treatment, that is, after the formal establishment of diabetic nephropathy model and after 4 weeks of traditional Chinese medicine treatment, 24-hour urine was collected twice using a rat metabolic cage, and the 24-hour urinary protein quantification was measured using a biochemical analyzer.

[0145] Renal function detection: Before and after drug administration and treatment, that is, after the formal establishment of diabetic nephropathy model and after 4 weeks of traditional Chinese medicine treatment, blood was collected from the medial canthus of the eye, left to stand for 30 minutes, centrifuged at 2500 r / min to obtain the supernatant of rat serum, stored at -20°C for later use, and renal function was measured using a biochemical analyzer: blood urea nitrogen and creatinine.

[0146] Observation of renal pathological histology (optical microscope):

[0147] After 4 weeks of intragastric administration of traditional Chinese medicine for treatment, the rats were sacrificed and part of the renal tissue was retained, fixed with 10% paraformaldehyde solution, dehydrated step by step with gradient alcohol, embedded in paraffin to make 4-μm sections, stained with HE and Masson, and the changes in glomeruli and renal interstitium were observed and photographed.

[0148] Observation of renal ultrastructure (electron microscope)

[0149] Rinse 3 times with 0.1M phosphate rinsing solution, fix with 1% osmium tetroxide fixing solution, and then rinse 3 times with 0.1 phosphate rinsing solution; dehydrate, embed, solidify, section with an ultramicrotome, double stain with 3% uranyl acetate-lead citrate, observe and take pictures with a transmission electron microscope.

[0150] The effects of the preparation of the present invention on urinary protein and renal function in rats with diabetic nephropathy are shown in Table 1. Table 1 Implementation Effect of Examples 1-4 on 24-hour urinary protein quantification and serum BUN and CR in diabetic nephropathy rats (mean ± S)

[0151]

[0152] Compared with the normal group, a P < 0.05, b P < 0.01, c P < 0.001;

[0153] Compared with the model group, d P < 0.05, e P < 0.01, f P < 0.001;

[0154] Compared with the basal group, g P < 0.05.

[0155] Changes in renal pathological histology (optical microscope)

[0156] Figures 1 to 8As shown, the kidneys of each group of rats were fixed, routinely embedded, sectioned, and observed after HE and MASSON staining. The results showed that, except for the normal group, the glomerular basement membranes of the other groups were thickened, the mesangial matrix proliferated, inflammatory cell infiltration occurred, and collagen fiber proliferation was observed, which was most obvious in the model group. The basic group and the invention group had varying degrees of improvement effects compared with the model group.

[0157] Changes in the ultrastructure of the kidney (electron microscope)

[0158] Figures 9 to 12 As shown: Normal group: Under the electron microscope, the foot processes separated from podocytes could be seen. The foot processes were clear without fusion, the basement membrane was intact, clear, uniform in thickness, without thickening, and the structure was clear.

[0159] Model group: Under the electron microscope, the foot processes separated from podocytes were fused into sheets and even shed. The basement membrane was homogeneously thickened and the structure was blurred.

[0160] Basic group and invention group: Under the electron microscope, it could be seen that the fusion of podocyte foot processes was significantly improved, and local foot processes returned to normal or close to normal; the thickening of the basement membrane was alleviated. The basic group had improvement, and the invention group had obvious improvement compared with the model group, and the invention group was close to normal.

[0161] Finally, it should be noted that: The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them; Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: They can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; And these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine composition for treating diabetic nephropathy, characterized in that: In parts by weight, the composition consists of the following components: 6 parts of ephedra, 6 parts of aconite, 12 parts of poria, 6 parts of atractylodes, 9 parts of cinnamon twig, 6 parts of licorice, 6 parts of dodder seed, 6 parts of leech, 6 parts of earthworm, 6 parts of mole cricket, 6 parts of schizonepeta tenuifolia, 15 parts of silkworm cocoon, 30 parts of pseudostellaria, and 45 parts of astragalus.

2. Use of the Chinese medicine composition according to claim 1 in preparing a drug for treating diabetic nephropathy.

3. A pharmaceutical preparation, characterized in that The pharmaceutical preparation is made from the Chinese medicine composition according to claim 1, or is made from the Chinese medicine composition according to claim 1 and pharmaceutically acceptable excipients.

4. The pharmaceutical preparation according to claim 3, characterized in that The dosage form of the pharmaceutical preparation is selected from tablets, granules, capsules, powders or solutions.

5. The method for preparing the pharmaceutical preparation according to claim 3, characterized in that: The preparation method steps are as follows: S01 classifying the components of the traditional Chinese medicine composition; S02 extracting components from the Chinese medicine composition classified in step S01; S03 preparing a pharmaceutical preparation from the components extracted in step S02; Wherein, in step S01, the classification is as follows: Group A: Ephedra, Poria, Licorice, Cuscuta, Pseudostellariae Radix, Astragalus; Group B: Atractylodes macrocephala and cinnamon twig; Group C: leeches, earthworms, mole crickets, and nine-scented insects; Group D: Silkworm cocoon and Aconitum.

6. The method for preparing the pharmaceutical preparation according to claim 5, characterized in that: The specific steps of step S02 are as follows: Groups A to E are respectively subjected to extraction of effective components, and then mixed.

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