Traditional Chinese medicine composition with effects of warming kidney, transforming qi and inducing diuresis to alleviate edema, preparation and application

Abstract

The invention discloses a traditional Chinese medicine composition with the effects of warming kidney, transforming qi and inducing diuresis to alleviate edema, a preparation and application. The traditional Chinese medicine composition is prepared from the following raw materials: black prepared rehmannia root, cinnamon, prepared rehmannia root, polyporus umbellatus, salvia miltiorrhiza and pericarpium arecae. The modern preparation is prepared by adding a certain amount of auxiliary materials through the technologies of modern extraction, filtration, concentration, drying and the like of traditional Chinese medicines, so that the accumulated medication experience of the traditional medicine is furthest reserved, and the traditional Chinese medicine composition has the advantages of convenience in taking, good taste and the like in the modern society. Meanwhile, in order to better characterize the quality of the obtained preparation, the obtained preparation is further subjected to pharmaceutical research, corresponding detection standards are formulated, and the content of components of the obtained preparation product is identified to meet the requirements through modern means so as to ensure that effective substances are fully extracted and utilized. The traditional Chinese medicine composition has the effects of warming kidney, transforming qi and inducing diuresis to alleviate edema, can be used for preparation or research and development of kidney-tonifying and yang-strengthening medicines, and has a good application prospect.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and specifically proposes a traditional Chinese medicine composition, preparation and application with the effects of warming the kidney and promoting qi circulation, and promoting diuresis and reducing swelling. Background Technology

[0002] Kidney Yang Deficiency Syndrome refers to a type of deficiency-cold syndrome caused by the decline of kidney yang, resulting in impaired warming function and dysfunction of qi transformation. Clinically, it is characterized by cold limbs and aversion to cold, lethargy, soreness and weakness of the lower back and knees, impotence and premature ejaculation. It is one of the important causes of male infertility.

[0003] The *Suwen Yipian Cifa Lun* states, "When righteous qi is abundant within, evil cannot invade." Traditional Chinese medicine theory holds that righteous qi is the foundation of the body's resistance to disease, maintaining bodily functions and ensuring the balance of yin and yang. Kidney qi is the root of this righteous qi, and among it, yang qi is crucial. The origin of yang qi in the body is kidney yang, which plays a leading role in the generation of kidney qi and is the source of yang qi, also known as the "fire of the gate of life." Traditional Chinese medicine believes that the kidneys store essence and govern growth, development, and reproduction. If kidney yang is deficient, its warming and transformative functions fail, resulting in insufficient essence production and internal heat scorching body fluids, leading to low sperm count, weak and infertile sperm. Therefore, providing a traditional Chinese medicine composition that can address infertility caused by kidney yang deficiency is one of the urgent technical problems to be solved. Clinically, most drugs used to treat male infertility caused by kidney yang deficiency are composed of herbs with drying properties, such as deer antler and seahorse. Long-term use leads to decreased patient compliance, and the herbs are expensive, which can be a significant burden for families with patients. Summary of the Invention

[0004] In view of this, the present invention proposes a cost-effective traditional Chinese medicine composition formula, which can be deeply explored in accordance with the requirements of modern traditional Chinese medicine technology, prepared into a modern formulation, and have formulation standards established. It maintains the quality of the original decoction, is convenient for patients to take, is particularly suitable for large-scale industrial production, and can be widely applied to the treatment of patients.

[0005] The technical solution of the present invention is implemented as follows: The present invention provides a traditional Chinese medicine composition with the effects of warming the kidney and promoting qi circulation, and promoting diuresis and reducing swelling, which is composed of black aconite slices, cinnamon, prepared rehmannia root, polyporus umbellatus, salvia miltiorrhiza and areca peel.

[0006] In some embodiments, the ingredients are composed of 6-8 parts by weight of aconite root slices, 8-10 parts of cinnamon, 6-8 parts of prepared rehmannia root, 8-12 parts of poria cocos, 6-8 parts of salvia miltiorrhiza, and 6-8 parts of areca peel.

[0007] In some embodiments, the ingredients are composed of 6 parts by weight of aconite root slices, 8 parts of cinnamon, 8 parts of prepared rehmannia root, 10 parts of poria cocos, 8 parts of salvia miltiorrhiza, and 7 parts of areca peel.

[0008] The above herbal formula is based on clinical practice regarding male infertility caused by kidney yang deficiency, and incorporates comprehensive innovations based on fundamental TCM theories. The formula consists of: dried aconite root slices, cinnamon bark, prepared rehmannia root, polyporus umbellatus, salvia miltiorrhiza, and areca peel. It originates from a modified version of Jisheng Shenqi Wan combined with Zhenwu Tang in *Zhang's Medical Treatise*, and has the effects of warming the kidneys, promoting qi circulation, and reducing edema. It is primarily used to treat kidney deficiency edema, infertility, lower back and knee fatigue, difficulty urinating, and cough with phlegm caused by kidney yang deficiency and internal dampness retention. The formula contains black aconite root slices, which are very hot in nature and can warm and tonify the spleen and kidney yang, and tonify fire and assist yang. Cinnamon is also very hot in nature and can help the black aconite root slices to tonify fire and assist yang. Rehmannia glutinosa nourishes yin and blood, benefits essence and fills marrow, complementing yin and yang, and tonifying yang without harming yin. Salvia miltiorrhiza invigorates blood and removes blood stasis, and improves blood circulation. Areca peel and Polyporus umbellatus have the effects of promoting diuresis and removing dampness, and strengthening the spleen and regulating qi. All of them enhance the function of strengthening the spleen, regulating qi and promoting diuresis. The whole formula works together to warm yang and tonify the kidney, strengthen the spleen and regulate qi.

[0009] In a second aspect, the present invention also provides a preparation made from the above-mentioned traditional Chinese medicine composition, wherein the preparation is one or more of the following: decoction, pill, elixir, medicated wine, tablet, and granule.

[0010] In some embodiments, the formulation is a granule, and the method for preparing the granule includes the following steps: (1) Weigh the raw materials according to the weight ratio, add water to extract 2-4 times, collect the extract, and filter to obtain the filtrate; (2) Concentrate the filtrate at 60-80℃ to obtain an extract with a relative density of 1.05-1.2; (3) Dry the extract to obtain a dry extract powder; (4) Mix the dry powder and excipients at a mass ratio of 2:1 and make granules by dry method.

[0011] In some embodiments, the excipients include one or a combination of several of the following: maltodextrin, dextrin, powdered sugar, povidone, polyethylene glycol, and β-cyclodextrin.

[0012] In some embodiments, the extraction is performed twice: the first extraction is performed with 10 times the amount of water for 60 minutes, and the second extraction is performed with 8 times the amount of water for 45 minutes. The two extracts are then combined and filtered through a 120-mesh filter.

[0013] The third aspect of this invention also provides a method for determining the content of the above-mentioned traditional Chinese medicine composition or preparation. The method involves determining the content of seven components, including phenolic acids and aconitines, using high-performance liquid chromatography (HPLC). These seven components include protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, benzoylneoprothiolane, salvianolic acid B, and benzoylneoprothiolane. Salvianolic acid B is a characteristic active ingredient of *Salvia miltiorrhiza*, and benzoylneoprothiolane is an effective ingredient of *Aconitum carmichaelii*. The total content of phenolic acids in the traditional Chinese medicine composition or preparation should be ≥10 mg / g, and the total content of aconitines should be ≥15 mg / g. These content standards ensure that the preparation achieves its kidney-warming and qi-regulating effects. The determination method steps are as follows: Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase; gradient elution was performed using acetonitrile and 0.2% phosphoric acid solution as the mobile phase, with the following volume ratios of acetonitrile in the mobile phase: 0-12 min, 5-15% acetonitrile; 12-28 min, 15-25% acetonitrile; 28-48 min, 25-35% acetonitrile; 48-49 min, 35-5% acetonitrile; 49-55 min, 5% acetonitrile; the detection wavelength was 203 nm. Preparation of reference solutions: Take appropriate amounts of protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, benzoyl aconitine, salvianolic acid B, and benzoyl aconitine reference standards, add methanol to the mark, and add methanol to prepare mixed reference solutions with concentrations of 19.5, 15.5, 14, 50, 220, 225, and 165 μg / mL. Shake well to obtain the solution. Preparation of the test solution: Accurately weigh 2.0 g of the powder, place it in a stoppered conical flask, add 25 ml of 50% methanol, sonicate for 30 min, and filter to obtain the solution; Determination method: Accurately pipette 3 μl of the reference solution and the test solution into the liquid chromatograph, measure and record the chromatogram to obtain the result.

[0014] The present invention also provides an application of the above-mentioned traditional Chinese medicine composition or preparation in the preparation of drugs with the effects of warming the kidney and promoting qi circulation, and promoting diuresis and reducing swelling.

[0015] In some embodiments, the drug is used to treat male infertility, functional edema, and cough and wheezing caused by kidney yang deficiency syndrome, with specific symptoms including soreness and weakness of the lower back and knees, aversion to cold and cold limbs, difficulty urinating, low sperm motility, and facial and limb edema; the drug is administered orally.

[0016] The present invention has the following advantages over the prior art: The traditional Chinese medicine composition prescription provided by this invention has the advantages of simplified formulation, small dosage, safety and reliability, and provides a relatively complete pharmaceutical quality control research standard. At the same time, it has good effects on increasing serum testosterone (T) level and the content of neural nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in penile tissue. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This invention provides a liquid phase diagram of the content determination of phenolic acids and aconitine in a sample for Example 2 of the present invention; Figure 2 This provides a linear correlation line between phenolic acid components and aconitine components in the sample for Example 2 of the present invention; Figure 3 This is a line graph showing the comparison of rectal temperature and body weight records of different groups in the rat adenine membrane formation method in Example 4 of the present invention; Figure 4 This is a comparative bar chart showing the serum testosterone (T), penile tissue eNOS and nNOS content records of different groups in the rat adenine membrane formation method in Example 4 of the present invention; Figure 5 This is a score chart comparing the scores of traditional Chinese medicine symptoms before and after treatment in Embodiment 5 of the present invention. Detailed Implementation

[0019] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of this invention pertain. If any definition stated in this section is contrary to or otherwise inconsistent with a definition stated in a patent, patent application, published patent application, or other publication incorporated herein by reference, the definitions listed here shall prevail over those incorporated herein by reference.

[0021] Unless otherwise specified, the methods used in the following embodiments are conventional methods. Unless otherwise specified, the materials, reagents, and instruments used are conventional materials, reagents, and instruments in the art, and can be obtained commercially by those skilled in the art.

[0022] When a quantity, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pair of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. For example, when the range “1 to 5” is disclosed, the described range should be interpreted as including ranges “1 to 4”, “1 to 3”, “1 to 2”, “1 to 2 and 4 to 5”, “1 to 3 and 5”, etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within that range. In this specification and claims, range definitions may be combined and / or interchanged, unless otherwise stated, these ranges include all subranges contained therein.

[0023] Example 1 This embodiment provides a solution for traditional Chinese medicine granules. The raw materials for a traditional Chinese medicine granulator are as follows: 6 parts (42g) of dried aconite slices, 8 parts (48g) of cinnamon, 8 parts (48g) of prepared rehmannia root, 10 parts (60g) of poria cocos, 8 parts (48g) of salvia miltiorrhiza, and 7 parts (42g) of areca peel, totaling 288g.

[0024] Preparation steps: Extraction: Weigh 42g of dried aconite slices, 48g of cinnamon, 36g of prepared rehmannia root, 72g of poria cocos, 36g of salvia miltiorrhiza, and 48g of areca peel, totaling 282g. First, add 10 times the amount of water (2880ml) and simmer for 60 minutes, then filter. Second, add 8 times the amount of water (2304ml) and simmer for 45 minutes, then filter. Combine the filtrates and filter through a 120-mesh sieve.

[0025] Concentration: Extract concentrated under reduced pressure at 70°C to a relative density of 1.10 (measured at 60°C).

[0026] Drying: Spray drying (inlet air 160℃, induced draft fan 50Hz, peristaltic pump 12rpm) yielded 82g of dry powder (yield 28.5%).

[0027] Granulation: Mix dry powder and maltodextrin in a ratio of 2:1 (82g:41g), granulate by dry method, pass through a 16-mesh sieve, and package into 3g / bags.

[0028] Example 2 Quality control methodology validation Three batches of granules were prepared according to the method in Example 1, numbered Sample 1, Sample 2, and Sample 3. The content of phenolic acids and aconitine compounds in the samples was determined and the method was validated according to the content determination methods in pharmaceutical quality standards. Chromatograms for the thin-film assay are attached. Figure 1 The relevant data for content determination are shown in Table 1 below. The total content of phenolic acids in each batch of samples is ≥ 10 mg / g, and the total content of aconitines is ≥ 15 mg / g. The precision test data are shown in Table 2. The peak area RSDs of protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, paeonol B, benzoylneoprothiolane, and benzoylneoprothiolane are all < 2.0%, indicating that the method meets the precision requirements. The stability test data are shown in Table 3. Within 20 hours of analysis, the RSD% of the peak area of ​​each measured component is less than 1.0%, indicating that the measured components are stable.

[0029] Table 1. Determination data of phenolic acid and aconitine content in the formulation granules

[0030] Table 2. Precision determination data of phenolic acids and aconitines in the formulation granules.

[0031] Table 3. Stability test data of phenolic acids and aconitine in the formulation granules

[0032] Example 3 Safety assessment The granules prepared in Example 1 above were subjected to acute toxicity studies in mice. Healthy KM mice, after a 16-hour fast, were randomly divided into a control group and a treatment group, with 20 mice in each group, based on weight and sex. The control group received 40 ml of 1% sodium carboxymethyl cellulose solution per kg of body weight via gavage twice, once at 9:00 a.m. and once at 3:00 p.m. The treatment group received 40 ml of the formulated granule solution per kg of body weight via gavage twice, once at 9:00 a.m. and once at 3:00 p.m. Weight changes were recorded for 14 days before and after treatment. General physiological characteristics (mental state, activity level, diet, bowel movements, and coat color) were observed, along with toxic reactions and the number of deaths. Any dead mice underwent immediate necropsy. On day 14, mice were weighed, euthanized by dislocation, and dissected. The appearance of major organs such as the heart, liver, spleen, lungs, and kidneys was visually examined. Any changes were investigated using histopathological examination.

[0033] Table 4 shows the weight gain of mice after administration of the test solution using the maximum dose method. The mice were active and in good spirits. After 14 days of observation, no abnormalities were observed in their diet or excrement, and no deaths occurred (Table 5). There was no statistically significant difference between the treated group and the corresponding blank control group (P > 0.05). Post-mortem examination of the heart, liver, spleen, lungs, and kidneys revealed no changes. The maximum dose for mice is 3.52 g contents / kg / day, equivalent to 58.6 times the maximum daily adult dose (3.6 g / 60 kg / day). At this dose, after 14 days of continuous observation, no obvious immediate or delayed toxic reactions were observed; all mice remained healthy and survived. These results indicate that the prescription drug has few or no toxic side effects and good safety, providing scientific support for the subsequent research and safety assessment of new drugs for treating male infertility caused by kidney yang deficiency.

[0034] Table 4. Changes in mouse body weight before and after administration in acute toxicity experiments (X±s, n=20)

[0035] Table 5. Changes in physical signs in mice 14 days after administration in the acute toxicity test (X±s, n=20)

[0036] Example 4 Pharmacodynamics-Male Infertility Model The granules prepared in Example 1 above were used in a pharmacodynamic study on rats. An appropriate amount of adenine was prepared into a film-forming solution of a certain concentration using 1% CMC-Na solution. Healthy male SD rats were randomly divided into two groups: a normal control group and a model group. The model group was administered the adenine film-forming solution by gavage, while the normal control group was administered an equal volume of 1% CMC-Na solution by gavage. After approximately one month of continuous administration, several rats from each group were randomly selected. Blood from the ocular sclera and epididymal tissue were collected to measure testosterone levels and observe sperm morphology. Simultaneously, the successful establishment of the kidney-yang deficiency model was indicated by the following physical signs in the model rats: emaciation, piloerection, arched back, dullness, and lethargy; and a significant decrease in serum testosterone levels and sperm viability (p<0.05).

[0037] After confirming successful model establishment, the remaining rats were randomly divided into: normal group, model group, Nanbao capsule group, low-dose group, medium-dose group, and high-dose group. The normal group and model group were administered 1% CMC-Na solution by gavage, while the other groups received the medication continuously for 30 days. During this period, the rats' hair, weight, activity level, mental state, and other symptoms and signs were observed every other day. Serum testosterone levels and eNOS and nNOS content in penile tissue were also measured to evaluate the effectiveness of the granules prepared with this prescription in improving the adenine-induced kidney-yang deficiency model in rats, including decreased body temperature, weakened sperm motility, and decreased serum testosterone and eNOS and nNOS content in penile tissue. This indicates that the prescription and its corresponding preparation have a good therapeutic effect on male infertility caused by kidney-yang deficiency. See Appendix for details. Figure 3-4 .

[0038] Example 5 Multiple indications clinical cases The granules prepared in Example 1 above were used in a clinical efficacy study in traditional Chinese medicine. Thirty patients diagnosed with kidney-yang deficiency using traditional Chinese medicine (TCM) were randomly divided into a control group and an observation group. The observation group received the prescribed granules, while the control group received oral furosemide tablets. The TCM syndrome scores (facial and limb edema, aversion to cold, lower back and knee weakness, and diarrhea, etc.), treatment effects (significantly effective, effective, and ineffective), and adverse reactions (including diarrhea, nausea, vomiting, and decreased appetite) were compared and analyzed. The treatment effects before and after treatment were compared using statistical analysis methods, and the TCM syndrome scores were statistically analyzed. See Tables 6-7 and Appendix for details. Figure 5 .

[0039] Table 6. Comparison of treatment effects between two different groups [n(%)]

[0040] Table 7 Comparison of adverse reactions between two different groups [n(%)]

[0041] The results showed that there was no statistically significant difference in TCM syndrome scores between the control group and the observation group before treatment (P>0.05). After treatment, the scores for aversion to cold, frequent urination, facial and limb edema, soreness and weakness of the lower back and knees, and diarrhea were lower than before treatment (P<0.05). The treatment effect in the observation group was higher than that in the control group (P<0.05). There was no statistically significant difference in the adverse reaction rate between the observation group and the control group (P>0.05). This indicates that this product has a good effect on improving kidney yin deficiency syndrome. Specific cases are as follows: Case 1 Mr. Tong, male, 62 years old, retired worker. The patient noticed facial and body edema one month ago, which worsened in the past two weeks, affecting the eyelids, face, and lower extremities. He also experienced lower back pain, fatigue, chills, and cold extremities. A urinalysis at another hospital was negative, and UREA, CR, and UA levels were all within the normal range. The edema improved after taking diuretics, but returned after discontinuing the medication. He requested treatment with traditional Chinese medicine.

[0042] Examination: The patient presented with an aged appearance, pale complexion, and edema of the eyelids, face, and lower limbs, with pitting edema that was difficult to remove upon palpation. Blood and urine routine tests, as well as heart, liver, and kidney function tests, were all normal. The tongue was pale and somewhat swollen, and the pulse was deep and thready. The diagnosis was functional edema (Western medicine) and edema (Traditional Chinese medicine), specifically due to kidney yang deficiency, impaired qi transformation of water, and internal accumulation of dampness. Treatment focused on warming and tonifying kidney yang, promoting qi transformation and water metabolism, and the proposed treatment was a granule preparation based on this prescription. Prescription: 6 parts of dried aconite root slices, 8 parts of cinnamon bark, 8 parts of prepared rehmannia root, 10 parts of polyporus umbellatus, 8 parts of salvia miltiorrhiza, and 7 parts of areca peel.

[0043] Take the above medicine twice daily. After half a month of medication, the facial and lower limb edema subsided, and the symptoms of coldness improved.

[0044] Case 2 The patient, a 35-year-old married man, reported feeling heavy and weak for the past year. He experienced shortness of breath after slight exertion, lower back pain, sensitivity to cold, facial swelling, and difficulty urinating. In the afternoon, he experienced swelling in his lower limbs.

[0045] Examination revealed pitting edema in the lower extremities, a pale tongue, and a deep, thready pulse. The patient had previously been treated at a hospital, taking traditional Chinese medicine such as Wupi Yin combined with Wuling San, and Western medicine treatments including diuretics, all without significant improvement. The edema subsided while taking the medication but recurred after discontinuation. All laboratory tests were normal.

[0046] Based on the above symptoms, tongue coating, and pulse, the TCM diagnosis is kidney yang deficiency with impaired water metabolism. Treatment principle: Warm and tonify kidney yang, promote diuresis and reduce swelling. Prescribe granules prepared according to this prescription. Take twice daily for half a month. Fifteen days later, at the follow-up visit, the patient reported a reduction in lower back pain, cold intolerance, edema, and diarrhea. After taking the medication for another half month, at the next follow-up visit, all symptoms had significantly lessened, the patient felt much lighter, and the lower back pain, leg weakness, coldness, and difficulty urinating had greatly improved, with the edema gradually subsiding. The patient was instructed to take the medication for another 10 days. At the second follow-up visit: all symptoms had completely disappeared.

[0047] Example 6 Validation of HPLC content determination method Chromatographic conditions: Chromatographic column: Octadecylsilane bonded silica column (C18 column, 250 mm × 4.6 mm, 5 μm).

[0048] Mobile phase: acetonitrile (A) and 0.2% phosphoric acid solution (B).

[0049] Gradient elution procedure: 0-12 minutes: Acetonitrile 5-15% (A).

[0050] 12-28 minutes: Acetonitrile 15-25% (A).

[0051] 28-48 minutes: Acetonitrile 25-35% (A).

[0052] 48-49 minutes: Acetonitrile 35-5% (A).

[0053] 49-55 minutes: Acetonitrile 5% (A).

[0054] Flow rate: 1.0 mL / min.

[0055] Detection wavelength: 203 nm.

[0056] Column temperature: 30℃.

[0057] Injection volume: 3 μL.

[0058] Preparation of the reference solution: Accurately weigh appropriate amounts of protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, benzoyl aconitine, salvianolic acid B, and benzoyl aconitine reference standards, and place them separately in 10 mL volumetric flasks.

[0059] Dissolve in methanol and dilute to the mark to prepare mixed reference solutions with concentrations of 19.5, 15.5, 14, 50, 220, 225, and 165 μg / mL. Shake well before use.

[0060] Preparation of the test solution: Accurately weigh 2.0 g of the powder and place it in a stoppered conical flask.

[0061] Add 25 mL of 50% methanol and sonicate for 30 minutes (power 250 W, frequency 40 kHz).

[0062] Filter the solution and use the filtrate as the test solution.

[0063] Determination method: Accurately pipette 3 μL each of the reference solution and the test solution and inject them into the liquid chromatograph, then record the chromatograms.

[0064] The content of each component is calculated based on peak area using the external standard method.

[0065] Results and Discussion: HPLC analysis showed that the total content of phenolic acid components in each batch of traditional Chinese medicine composition was ≥10 mg / g, and the total content of aconitine components was ≥15 mg / g.

[0066] In the precision experiment, the RSD of the peak area of ​​each component was <2.0%, indicating that the method has good precision and repeatability.

[0067] In the stability test, the RSD of the peak area of ​​each component was <1.0% within 20 hours, indicating that the test solution was stable within 20 hours.

[0068] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition with the effects of warming the kidneys and promoting qi circulation, and promoting diuresis and reducing edema, characterized in that, It is composed of black aconite slices, cinnamon, prepared rehmannia root, poria cocos, salvia miltiorrhiza, and areca peel.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, Based on weight, it consists of 6-8 parts of dried aconite slices, 8-10 parts of cinnamon, 6-8 parts of prepared rehmannia root, 8-12 parts of poria cocos, 6-8 parts of salvia miltiorrhiza, and 6-8 parts of areca peel.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, Based on weight, it consists of 6 parts of dried aconite root slices, 8 parts of cinnamon, 8 parts of prepared rehmannia root, 10 parts of poria cocos, 8 parts of salvia miltiorrhiza, and 7 parts of areca peel.

4. A formulation prepared from a traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The preparation is one or more of the following: decoction, pill, elixir, medicated wine, tablet, and granule.

5. The formulation as described in claim 4, characterized in that, The formulation is a granule, and the preparation method of the granule includes the following steps: (1) Weigh the raw materials according to the weight ratio, add water to extract 2-4 times, collect the extract, and filter to obtain the filtrate; (2) Concentrate the filtrate at 60-80℃ to obtain an extract with a relative density of 1.05-1.2; (3) Dry the extract to obtain a dry extract powder; (4) Mix the dry powder and excipients at a mass ratio of 2:1 and make granules by dry method.

6. The formulation as described in claim 5, characterized in that, The excipients include one or a combination of several of the following: maltodextrin, dextrin, powdered sugar, povidone, polyethylene glycol, and β-cyclodextrin.

7. The formulation according to claim 6, characterized in that, The extraction was performed twice. The first extraction was performed with 10 times the amount of water for 60 minutes, and the second extraction was performed with 8 times the amount of water for 45 minutes. The two extracts were combined and filtered through a 120-mesh filter.

8. A method for determining the content of a traditional Chinese medicine composition according to any one of claims 1-3 or a preparation according to any one of claims 4-7, characterized in that, The content of seven components, including phenolic acids and aconitines, was determined by high performance liquid chromatography. These seven components include protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, benzoylneoprothiolane, salvianolic acid B, and benzoylneoprothiolane. Among them, salvianolic acid B is the characteristic active ingredient of tanshinone, and benzoylneoprothiolane is the effective ingredient of aconite root extract. The total content of phenolic acids in the traditional Chinese medicine composition or preparation should be ≥10 mg / g, and the total content of aconitines should be ≥15 mg / g. The content standards ensure that the preparation meets the requirements for warming the kidney and promoting qi circulation. The determination method steps are as follows: Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase; Gradient elution was performed using acetonitrile and 0.2% phosphoric acid solution as the mobile phase. The volume ratios of acetonitrile in the mobile phase were as follows: 0-12 min, 5-15% acetonitrile; 12-28 min, 15-25% acetonitrile; 28-48 min, 25-35% acetonitrile; 48-49 min, 35-5% acetonitrile; 49-55 min, 5% acetonitrile. The detection wavelength was 203 nm. Preparation of reference solutions: Take appropriate amounts of protocatechuic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, rosmarinic acid, benzoyl aconitine, salvianolic acid B, and benzoyl aconitine reference standards, add methanol to the mark, and add methanol to prepare mixed reference solutions with concentrations of 19.5, 15.5, 14, 50, 220, 225, and 165 μg / mL. Shake well to obtain the solution. Preparation of the test solution: Accurately weigh 2.0 g of the powder, place it in a stoppered conical flask, add 25 ml of 50% methanol, sonicate for 30 min, and filter to obtain the solution; Determination method: Accurately pipette 3 μl of the reference solution and the test solution into the liquid chromatograph, measure and record the chromatogram to obtain the result.

9. The use of any of the traditional Chinese medicine compositions according to claims 1-3 or any of the preparations according to claims 4-7 in the preparation of drugs with the effects of warming the kidneys and promoting qi circulation, and promoting diuresis and reducing edema.

10. The application as described in claim 9, characterized in that, The drug is used to treat male infertility, functional edema, and cough and asthma caused by kidney yang deficiency syndrome.

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