Traditional Chinese medicine mixture with effect of tonifying liver and kidney and preparation method of traditional Chinese medicine mixture

Abstract

The invention discloses a traditional Chinese medicine mixture with a liver and kidney tonifying effect and a preparation method thereof, and belongs to the field of pharmaceutical preparations. The traditional Chinese medicine mixture comprises the following components in parts by weight: 45-60 parts of polygonum multiflorum; 45-60 parts of rhizoma polygonati; 110 to 130 parts of fructus rosae laevigatae; 2.4 to 3.2 parts of Chinese angelica; 45-60 parts of rhizoma cibotii; 3.2 to 3.8 of semen cuscutae; 1.8-2.4 parts of dried orange peel; 3.5 parts of fructus psoraleae; the preparation method of the traditional Chinese medicine mixture comprises the following steps: decocting the components in water, filtering, concentrating filtrate until the density is 1.10-1.16 g / mL, adding ethanol until the alcohol content is 60%, standing for 24 hours, taking supernate, filtering, and recovering the filtrate under reduced pressure until no alcohol exists; adding water to 120 parts by weight, adding 2 parts by weight of talcum powder and 1 part by weight of sodium benzoate, uniformly stirring, and standing for 24-48 hours; taking supernatant liquid, adding 120-150 parts by weight of cane sugar, adding water to 300-350 parts by weight, uniformly stirring, boiling, standing and filtering to obtain filtrate, namely the product mixture. Eight medicines of the traditional Chinese medicine mixture are applied dialectically, and complement each other in tonifying liver and kidney, invigorating spleen and replenishing qi, arresting seminal emission and arresting enuresis.

Description

TECHNICAL FIELD

[0001] The present application relates to a traditional Chinese medicine mixture with the effect of tonifying liver and kidney and a preparation method thereof, and belongs to the field of pharmaceutical preparations. BACKGROUND

[0002] Modern medicine believes that the key to sub-health care is to prevent and adjust the body's health. Traditional Chinese medicine believes that the kidney is the root of the body, and is responsible for growth, development, reproduction and the physiological activities between organs. In the process of human life at all stages, the physiological state at different periods is determined by the rise and fall of kidney essence. If the kidney is strong, the essence is abundant, the body is light, the hair is black and shiny, the face is rosy, and the appearance is pleasant. If the kidney is weak, it will show symptoms such as soreness and pain in the waist and knees, infertility in women, fatigue, decreased sexual desire, cold limbs, dizziness, insomnia, poor spirit, lack of strength, amenorrhea in women, oligospermia in men, physical weakness, pale complexion, yellowish complexion, hair loss, tooth loss, frequent childbirth and abortion in women, irregular menstruation, chronic illness, overthinking and overwork in men, and excessive sexual activity, overwork, and loss of essence and qi. If it is not treated in time, the original qi, which is the original qi of the human body, is stored in the kidney, which is kidney qi. Kidney qi is distributed throughout the body, has the function of nourishing the limbs and various tissues and organs, and promotes blood circulation, so that the organs, meridians and other tissues and organs maintain normal physiological activities. Therefore, the original qi is the fundamental qi of the human body, the material basis of the original driving force of life activities, and the most important basic material for maintaining life activities. Therefore, the body's original qi is abundant, the quality is strong, the activities of various organs, meridians and other tissues and organs are vigorous, and thus the health is less disease. If the innate endowment is insufficient, or due to postnatal imbalance, or due to long-term illness and loss, the generation or loss of original qi will be too much, resulting in weak original qi, leading to disease, and even endangering life.

[0003] The kidney and essence mixture has the effects of tonifying liver and kidney and invigorating spleen and qi, and is mainly used for dizziness, tinnitus, soreness and weakness of the waist and knees, etc. caused by liver and kidney deficiency and spleen and qi deficiency. The original standard is recorded in the "Ministry of Health of the People's Republic of China Drug Standards" traditional Chinese medicine prescription preparations, which are refined from radix rehmanniae, fructus rosae laevigatae, rhizoma polygonati, fructus psoraleae, dog spine, angelica sinensis, cuscuta chinensis and pericarpium citri reticulatae. It has the effects of tonifying liver and kidney and invigorating spleen and qi.

[0004] Chinese medicine mixture is a kind of liquid preparation for internal use, which is prepared by extracting and concentrating medicinal materials with water or other solvents, and is packaged as a single dose for oral use. This dosage form is modified from traditional decoction, and has fixed preparation process and quality control standards, and can be produced in batches and has reliable clinical efficacy. It has the characteristics of saving temporary decoction, small volume, high concentration, and convenience for carrying and storage, but cannot replace the function of adding or subtracting according to symptoms of decoction. The preparation process includes five steps of immersion, purification, concentration, sub-packaging and sterilization. Attention should be paid to the extraction of volatile components and the preservation treatment during production. The finished product should not appear rancid and deteriorated, and can contain a small amount of light shaking and scattered sediment, and the package should be marked with "shake well before taking". The quality control covers the detection of relative density and pH value, and specifies the sealed storage condition in cool place. SUMMARY

[0005] The present application aims to provide a Chinese medicine mixture with the effect of tonifying liver and kidney Another object of the present application is to provide a preparation method of the Chinese medicine mixture with the effect of tonifying liver and kidney.

[0006] The Chinese medicine mixture with the effect of tonifying liver and kidney comprises the following components by weight: Radix Polygoni Multiflori 45-60; Rhizoma Polygonati 45-60; Fructus Rosae Laevigatae 110-130; Angelica 2.4-3.2; Dipsacus 45-60; Semen Litchi 3.2-3.8; Pericarpium Citri Reticulatae Viride 1.8-2.4; Fructus Psoraleae 3.5.

[0007] Pleuropterus multiflorus (Thunb.) Turcz. ex Nakai, a perennial herb, is native to China, Thailand, and Vietnam, and has been introduced to Japan, South Korea, and the Caucasus region. It is mainly distributed in southern Shaanxi, southern Gansu, East China, Central China, and South China. It grows in valleys, slopes, and gully edges at an altitude of 200-3000 meters. It prefers warm and humid climate, and is tolerant to shade and drought, but not waterlogging. It grows well in sandy soil with deep, loose, fertile, and humid texture. The root and leaf of P. multiflorus can be used as traditional Chinese medicine. The root has the functions of nourishing blood and yin, moistening the intestines, and relieving constipation, and is used to treat dizziness, palpitation, insomnia, soreness of the waist and knees, premature graying of hair, tinnitus, and spermatorrhea. The leaf has the functions of detoxifying, resolving masses, killing insects, and relieving itching, and is used to treat sores, scabies, and other diseases.

[0008] Rosa laevigata Michx., a climbing shrub of Rosaceae, is used as traditional Chinese medicine. It is mainly distributed in Shaanxi, Anhui, Jiangxi, and other provinces. It grows in shrubs at an altitude of 200-1600 meters. The ripe fruit is harvested from October to November, and is used after removing the hairs. It tastes sour, sweet, and astringent, and is neutral in nature. It belongs to the kidney, bladder, and large intestine channels. It has the functions of consolidating essence, shrinking urine, arresting bleeding, and astringing the intestines. It is used to treat spermatorrhea, frequent urination, chronic diarrhea, and other diseases. According to Bencao Xinbian, it should be combined with water-reducing herbs such as Euryale ferox and Dioscorea opposita to enhance the efficacy and prevent the blockage of the essence orifice.

[0009] Polygonatum sibiricum Delar. ex Redoute is a perennial herb of Asparagales, Liliaceae, Polygonatum, with rhizomes and swollen nodes; whorled leaves, 4-6 per whorl, lanceolate, with rolled or hooked tips; 2-4-flowered, often umbel-like, with long, pendent pedicels; bracts membranous, lanceolate or lanceolate-elliptic; corolla white or yellowish, with a slightly constricted tube; black when ripe. Flowering from May to June, fruiting from August to September. According to Baopoz i, “ancient people obtained the essence of the earth and the universe from this plant, hence the name.” The main producing area of Polygonatum sibiricum is China, with distribution in Korea, Mongolia and eastern Siberia of the Soviet Union. Polygonatum sibiricum grows in grasslands, shady slopes, undergrowth, shrubs at an altitude of 800-2800 meters, and rarely in alpine regions, cliff bottoms and valleys. Polygonatum sibiricum prefers warm and humid climates and shady environments, is cold-tolerant, likes moisture, and is not drought-tolerant. It is suitable for cultivation in sandy loam soil with deep, loose, fertile, well-drained and moist conditions. The active ingredients in Polygonatum sibiricum include polysaccharides, flavonoids, saponins, alkaloids, amino acids and trace elements. The rhizome of Polygonatum sibiricum can be used as medicine, with a sweet taste, neutral property, and entering the spleen, lung and kidney meridians. It has the effects of nourishing yin and moistening the lungs, tonifying the spleen and replenishing qi, and nourishing the kidney and filling essence.

[0010] Cullen corylifolium (Linnaeus) Medikus is an annual herb of Leguminosae, Cullen, 1.5 meters tall. The whole plant is covered with white soft hair and black-brown glandular spots; the stem is erect; the leaf blade is nearly leathery, wide ovate; the calyx is bell-shaped, with lance-shaped lobes; the corolla is pale purple or white, with a flag petal that is inversely ovate, and wing and keel petals that are nearly equal in length; the pod is oval. Cullen corylifolium was first recorded in Lei Gong's Theory of Medicinal Decoction. It is native to China, distributed in Hebei, Shanxi, Gansu, Guangdong, Guangxi and Guizhou, and also distributed in India, Myanmar and Sri Lanka. It often grows on slopes, by streams and in fields. Cullen corylifolium prefers warm, humid and sunny environments, is not tolerant to waterlogging, and is suitable for sandy loam soil rich in humus. The main propagation method is seed propagation. According to the Compendium of Materia Medica, Cullen corylifolium can “treat kidney leakage, open the gate of life, warm the lower abdomen, and condense spirit.” It contains flavonoids, coumarins, monoterpenes and other chemical components, and has the effects of anti-implantation, enhancing the body's immunity, hemostasis and anti-cancer.

[0011] Woodwardia japonica (L. F.) Sm. is a perennial large fern of the family Thelypteridaceae. The plant is up to 1.2 meters high; rhizome is stout and horizontal, dark brown, with the base of the petiole densely covered with entire dark brown lanceolate or linear lanceolate scales; petiole is hard and dark brown, blade is long ovate, bipinnate, top pinnae are ovate lanceolate or long triangular lanceolate, leaf is brown or brown green after drying; sporangium is linear, arranged in single row and discontinuous on both sides of the narrow long mesh of the main vein; indusium is isomorphic, opening to the main vein or the pinna axis; because of its long and multiple roots, it looks like a dog's spine, hence the name "dog spine". Woodwardia japonica is widely distributed in the provinces and regions south of the Yangtze River in China, southern Korea and Japan. It prefers cool and humid environment and hates direct sunlight. It grows in acid soil at the foot of the mountain and under the forest. Woodwardia japonica is not endangered (LC) in the Red List of Endangered Species of the World Conservation Union. It is usually propagated by division or spores. The rhizome of Woodwardia japonica can be used as medicine. According to Bencao Zixin, "Woodwardia japonica can strengthen the liver and kidney, and tonify qi". It tastes bitter and sweet, and is warm in nature, belonging to the liver and kidney channels, with the functions of tonifying the liver and kidney, strengthening the waist and knees, dispelling wind and dampness, mainly used for treating waist pain, joint stiffness, back pain, incontinence, and other symptoms caused by liver and kidney deficiency and wind and cold dampness.

[0012] Angelica sinensis (Oliv.) Diels is a perennial herb of the Apiaceae family. The root is cylindrical, branched, yellowish brown; the stem is erect, greenish white or purple, with longitudinal deep grooves; the leaves are pinnately divided, purple or green, ovate; the flowers are white, with dense fine pubescence on the pedicel, the petals are long ovate, the style base is conical, the flowering period is from June to July. The fruit is oval to ovate, with light purple edges of the wing, the fruiting period is from July to September. According to the Compendium of Materia Medica, "Ancient people married women to continue the family line. Angelica sinensis regulates blood, is a woman's essential medicine, has the meaning of thinking of her husband, hence the name Angelica sinensis". Angelica sinensis is mainly produced in southeastern Gansu, with large output and good quality in Minxian County, followed by Yunnan, Sichuan, Shaanxi and Hubei provinces, all of which are cultivated, and some provinces have also introduced and cultivated it. It prefers cool and cold, and grows in cold and humid mountainous areas. Generally, it is propagated by sowing seeds and transplanting seedlings, and often by transplanting seedlings in production. Angelica sinensis has a long history of medicine, and was recorded in the first pharmacological monograph of China, Shennong Bencao Jing. Because of its great effect, many traditional Chinese medicine prescriptions cannot do without Angelica sinensis, hence the saying "ten prescriptions nine Angelica sinensis". Angelica sinensis has the functions of regulating and tonifying blood, and is known as "the holy medicine of blood", even being respected as "the king of medicine".

[0013] Cuscuta chinensis Lam. is a parasitic plant of the Cuscuta genus of the Convolvulaceae family, widely distributed in many countries in Asia. It has been recorded in Shennong Bencao Jing since ancient times, and has the effects of tonifying liver and kidney, astringing essence and urine, preventing miscarriage, improving eyesight and stopping diarrhea.

[0014] Pericarpium Citri Reticulatae is the dried pericarp of the fruit of the orange tree. The pericarp can be stored for a long time if kept dry, hence the name Pericarpium Citri Reticulatae. According to traditional Chinese medicine, Pericarpium Citri Reticulatae is acrid, bitter and warm in nature, and enters the spleen and lung channels. It has the functions of regulating qi, strengthening the spleen, descending adverse qi, stopping vomiting, regulating the middle energizer, drying dampness and reducing phlegm. It is used to treat abdominal distention, belching, nausea, vomiting, poor appetite, lassitude, loose stool and other symptoms. Adding Pericarpium Citri Reticulatae to diet has the effect of strengthening the spleen and stomach.

[0015] In the preferred embodiment of the present application, the Chinese medicine mixture comprises the following components by weight: Radix Polygoni Multiflori 52; Rhizoma Polygonati 52; Fructus Rosae Laevigatae 121; Radix Angelicae Sinensis 2.8; Caulis Tetrapanacis 52; Semen Luffae 3.5; Pericarpium Citri Reticulatae 2.1; Fructus Psoraleae 3.5.

[0016] The solid product of the above Chinese medicine mixture further comprises the following components by weight: Sucrose 150; Sodium Benzoate 1; Talcum 2.

[0017] The preparation method of the Chinese medicine mixture comprises the following steps: placing Radix Polygoni Multiflori, Rhizoma Polygonati, Fructus Rosae Laevigatae, Radix Angelicae Sinensis, Caulis Tetrapanacis, Semen Luffae, Pericarpium Citri Reticulatae and Fructus Psoraleae in 3000 parts by weight of water and decocting for 1-2 hours, filtering, and reserving the filtrate; adding water to the residue to 3000 parts by weight, continuing to decoct for 1-2 hours, filtering, combining the filtrates, concentrating to a density of 1.10-1.16 g / mL, adding ethanol to an alcohol content of 60%, standing for 24 hours, taking the supernatant, filtering, and recovering the filtrate under reduced pressure to remove ethanol.

[0018] In the preferred embodiment, after the filtrate is recovered under reduced pressure to remove ethanol, water is added to 120 parts by weight, talcum is added to 2 parts by weight, and sodium benzoate is added to 1 part by weight, and the mixture is stirred uniformly and stood for 24-48 hours.

[0019] In the preferred embodiment, after the standing for 24-48 hours, the upper clear liquid is taken, sucrose is added to 120-150 parts by weight, and water is added to 300-350 parts by weight, and the mixture is stirred uniformly.

[0020] In the preferred embodiment, after the stirring, the mixture is boiled, stood and filtered, and the filtrate is the product mixture.

[0021] In the preferred embodiment, in the preparation method, the amount of sucrose added is 150 parts by weight.

[0022] In the preparation method, the water is added to 350 parts by weight.

[0023] In the Chinese medicine mixture, the Chrysanthemum morifolium Ramat. is used to play the role of the monarch drug for tonifying kidney, retaining essence and absorbing essence; the Polygoni Multiflori Radix, the Cibotium barometz and the Psoralea Corylifolia L. are mutually synergistic, tonifying kidney, tonifying liver, nourishing blood, assisting yang, strengthening waist and knees, absorbing qi to relieve asthma, and warming spleen to stop diarrhea, playing the role of ministerial drugs; the Polygoni Multiflori Radix can tonify liver and kidney, nourish blood, and is used for liver-kidney yin deficiency, early graying, dizziness due to blood deficiency, weakness of waist and knees, and soreness of joints and bones; modern pharmacological research shows that the Polygoni Multiflori Radix can promote hematopoietic function, improve immune function of the body, lower blood lipids, resist atherosclerosis, protect liver, delay aging, regulate endocrine function, moisten the intestines and defecate, etc.; the Angelica sinensis can tonify blood, activate blood, regulate menstruation and relieve pain, moisten the intestines and defecate; the Polygonatum can moisten the lung, nourish yin, tonify the spleen and invigorate qi; the Cuscuta chinensis Lam. can tonify liver and kidney, astringe essence, reduce urine, improve eyesight and stop diarrhea, playing the role of assistant drugs; the Pericarpium Citri Reticulatae can regulate qi, invigorate the spleen, dry dampness, regulate qi movement, and move qi to the disease site, playing the role of emissary drug; the eight kinds of drugs are used according to syndrome differentiation, tonifying liver and kidney, invigorating the spleen and qi, and astringing essence to stop leakage, and the effects are more obvious. DETAILED DESCRIPTION

[0024] The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.

[0025] Embodiment 1 The following raw medicinal materials were taken: Polygoni Multiflori Radix 52 g Polygonatum 52 g Chrysanthemum morifolium Ramat. 121 g Angelica sinensis 2.8 g Cibotium barometz 52 g Cuscuta chinensis Lam. 3.5 g Pericarpium Citri Reticulatae 2.1 g Psoralea Corylifolia L. 3.5 g were placed in 3 L of water for decoction for 2 hours, filtered, and the filtrate was prepared; the filter residue was added with water to 3 L for continuous decoction for 2 hours, filtered, and the filtrates were combined, concentrated to a density of 1.15 g / mL, added with ethanol to an alcohol content of 60%, and statically placed for 24 hours; the supernatant was taken, filtered, and the filtrate was recovered under reduced pressure to be alcohol-free. Water was added to 120 mL, added with talc 2 g and sodium benzoate 1 g, stirred uniformly, statically placed for 48 hours, the upper clear liquid was taken, added with sucrose 150 g, added with water to 350 mL, stirred uniformly, boiled, statically placed for filtration, and the filtrate was the product mixture.

[0026] Embodiment 2 The following raw medicinal materials were taken: Radix Polygoni Multiflori 50g Rhizoma Polygonati 54g Fructus Rosae Laevigatae 123g Radix Angelicae Sinensis 2.9g Caulis Dipsacri 45g Semen Eurycoma 3.2g Pericarpium Citri Reticulatae 2.0g Fructus Psoraleae 3.5g Decoction for 2 hours, filter, filter ready for use; filter residue add water to 3L continue decoction for 2 hours, filter, combined filtrate, concentrated to density of 1.12g / mL, add ethanol to contain alcohol amount of 60%, stand for 24 hours, take supernatant, filter, filter reduced pressure recovery to no alcohol. Add water to 120mL, add talc 2g, sodium benzoate 1g, stir evenly, stand for 48 hours, take upper clear liquid, add sucrose 150g, add water to 350mL, stir evenly, boil, stand for filter, filtrate is the product mixture.

[0027] Example 3 Take the following raw materials: Radix Polygoni Multiflori 48g Rhizoma Polygonati 57g Fructus Rosae Laevigatae 126g Radix Angelicae Sinensis 3.0g Caulis Dipsacri 48g Semen Eurycoma 3.3g Pericarpium Citri Reticulatae 1.9g Fructus Psoraleae 3.5g Decoction for 2 hours, filter, filter ready for use; filter residue add water to 3L continue decoction for 2 hours, filter, combined filtrate, concentrated to density of 1.14g / mL, add ethanol to contain alcohol amount of 60%, stand for 24 hours, take supernatant, filter, filter reduced pressure recovery to no alcohol. Add water to 120mL, add talc 2g, sodium benzoate 1g, stir evenly, stand for 48 hours, take upper clear liquid, add sucrose 150g, add water to 350mL, stir evenly, boil, stand for filter, filtrate is the product mixture.

[0028] Example 4 Take the following raw materials: Radix Polygoni Multiflori 45g Rhizoma Polygonati 60g Fructus Rosae Laevigatae 130g Radix Angelicae Sinensis 3.2g Caulis Dipsacri 52g Semen Eurycoma 3.6g Pericarpium Citri Reticulatae 1.8g Fructus Psoraleae 3.5g Put in 3L water decoct 2 hours, filter, filtrate for standby; filter residue add water to 3L continue decoct 2 hours, filter, combine filtrate, concentrate to density 1.13g / mL, add ethanol to alcohol content 60%, stand 24 hours, take supernatant, filter, filtrate reduce pressure recovery to no alcohol. Add water to 120mL, add talc powder 2g, sodium benzoate 1g, stir uniform, stand 48 hours, take upper clear liquid, add sucrose 150g, add water to 350mL, stir uniform, boil, stand filter, filtrate is product mixture.

[0029] Example 5 Take the following raw material: Radix Polygoni Multiflori 55g Rhizoma Polygonati 51g Fructus Rosae Laevigatae 118g Angelica sinensis 2.6g Dipsacus asper 56g Semen Euryale Ferri 3.7g Citrus reticulata 2.2g Fructus Psoraleae 3.5g Put in 3L water decoct 2 hours, filter, filtrate for standby; filter residue add water to 3L continue decoct 2 hours, filter, combine filtrate, concentrate to density 1.16g / mL, add ethanol to alcohol content 60%, stand 24 hours, take supernatant, filter, filtrate reduce pressure recovery to no alcohol. Add water to 120mL, add talc powder 2g, sodium benzoate 1g, stir uniform, stand 48 hours, take upper clear liquid, add sucrose 150g, add water to 350mL, stir uniform, boil, stand filter, filtrate is product mixture.

[0030] Example 6 Take the following raw material: Radix Polygoni Multiflori 57g Rhizoma Polygonati 47g Fructus Rosae Laevigatae 115g Angelica sinensis 2.4g Dipsacus asper 58g Semen Euryale Ferri 3.8g Citrus reticulata 2.3g Fructus Psoraleae 3.5g Put in 3L water decoct 2 hours, filter, filtrate for standby; filter residue add water to 3L continue decoct 2 hours, filter, combine filtrate, concentrate to density 1.15g / mL, add ethanol to alcohol content 60%, stand 24 hours, take supernatant, filter, filtrate reduce pressure recovery to no alcohol. Add water to 120mL, add talc powder 2g, sodium benzoate 1g, stir uniform, stand 48 hours, take upper clear liquid, add sucrose 150g, add water to 350mL, stir uniform, boil, stand filter, filtrate is product mixture.

[0031] Example 7 Take the following raw materials: Radix Polygoni Multiflori 60 g Rhizoma Polygonati 45 g Fructus Rosae Laevigatae 110 g Radix Angelicae Sinensis 2.8 g Caulis Dipsacri 60 g Semen Luffae 3.8 g Pericarpium Citri Reticulatae Viride 2.4 g Fructus Psoraleae 3.5 g Place in 3L water and decoct for 2 hours, filter, and reserve the filtrate; add water to the filter residue to 3L and continue to decoct for 2 hours, filter, combine the filtrates, concentrate to a density of 1.13g / mL, add ethanol to a content of 60%, stand for 24 hours, take the supernatant, filter, and recover the filtrate under reduced pressure to be alcohol-free. Add water to 120mL, add talc 2g and sodium benzoate 1g, stir to be uniform, stand for 48 hours, take the upper clear liquid, add sucrose 150g, add water to 350mL, stir to be uniform, boil, stand to filter, and the filtrate is the product mixture.

[0032] Experimental Example 1 This experimental example uses HPLC method to determine the content of psoralen and isopsoralen in the mixture of Example 1 Method: Agilent ZORBAX SB-C18 chromatographic column (250 mm × 4.6 mm, 5 μm) is used, acetonitrile-0.1% phosphoric acid aqueous solution (25:75) is used as the mobile phase for isocratic elution, the flow rate is 1.0 mL / min, the detection wavelength is 245 nm, the column temperature is 30℃, and the injection volume is 10 μL.

[0033] The mixture of Example 1 is a Chinese patent drug, and Fructus Psoraleae is one of the main medicinal ingredients in the prescription. The effective components of psoralen and isopsoralen (collectively referred to as furanocoumarins) are important index components for evaluating the quality of the preparation.

[0034] High performance liquid chromatography has the advantages of high separation efficiency, fast analysis speed, and accurate results, and has been widely used in the content determination of traditional Chinese medicine preparations. In order to better control the internal quality of the mixture and ensure the stability and uniformity of its clinical efficacy, this experimental example establishes an HPLC method for simultaneously determining the content of psoralen and isopsoralen, and systematically verifies the methodology. The method has strong specificity, high sensitivity, and good reproducibility, and provides a scientific basis for perfecting the quality standard of the preparation.

[0035] Instruments and reagents Instruments Agilent 1260 type high performance liquid chromatography system (configured with DAD detector); XP205 type electronic analytical balance (Mettler-Toledo); KQ-500DE digital ultrasonic cleaner (Kunshan Ultrasonic Instrument Co., Ltd.).

[0036] Medicament Psoralen reference substance (China Institute for Drug Control, batch number: 110739-202356, purity: 98.5%); Isopsoralen reference substance (China Institute for Drug Control, batch number: 110740-202367, purity: 98.2%); Test sample: product of Example 1; Acetonitrile was chromatographically pure; Water was ultrapure water; The rest of the reagents were analytically pure.

[0037] Method and results Chromatographic conditions Chromatographic column: Agilent ZORBAX SB-C18 (250 mm × 4.6 mm, 5 μm); mobile phase: acetonitrile-0.1% phosphoric acid aqueous solution (25:75); flow rate: 1.0 mL / min; detection wavelength: 245 nm; column temperature: 30℃; sample injection volume: 10 μL.

[0038] Under these chromatographic conditions, the theoretical plate number was not less than 5000 according to the psoralen peak, and the separation degree between psoralen and isopsoralen and each adjacent chromatographic peak was greater than 1.5.

[0039] Preparation of solutions Reference solution A suitable amount of psoralen and isopsoralen reference substances was precisely weighed, and methanol was added to prepare a mixed reference solution containing 25.6 μg of psoralen and 24.8 μg of isopsoralen per 1 mL, respectively.

[0040] Test sample solution 5 mL of the product of Example 1 was precisely measured into a 25 mL volumetric flask, methanol was added to near the calibration mark, and ultrasonic treatment (power 500 W, frequency 40 kHz) was performed for 30 minutes. After taking it out and cooling, methanol was added to dilute to the calibration mark, shaken well, filtered with a microporous filter membrane (0.45 μm), and the filtrate was taken, i.e. the test sample solution was obtained.

[0041] Negative sample solution A negative sample without psoralen component was prepared according to the process of Example 1, and the negative sample solution was prepared according to the method under the item of "test sample solution".

[0042] Methodology validation specificity test Take the control solution, test solution and negative sample solution respectively, and determine by injecting sample under the chromatographic conditions. The results show that in the test sample chromatogram, there are the same chromatographic peaks at the retention time corresponding to the psoralen and isopsoralen control sample chromatogram, and the negative sample has no interference, indicating that the method has good specificity.

[0043] Linear relationship investigation Precisely weigh an appropriate amount of control sample, dilute with methanol to prepare a series of mixed control sample solutions with different concentrations, and determine by injecting sample under the chromatographic conditions. Take the peak area (Y) as the ordinate and the control sample concentration (X, μg / mL) as the abscissa to perform linear regression. The regression equations are: Psoralen: Y = 12345.6 X + 25.8, r = 0.9998 Isopsoralen: Y = 13456.7 X + 18.3, r = 0.9999 The results show that psoralen and isopsoralen have good linear relationships in the concentration ranges of 5.56 ~ 56.20 μg / mL and 6.48 ~ 99.60 μg / mL, respectively.

[0044] Precision test Take the same control sample solution, inject sample continuously for 6 times according to the chromatographic conditions, and record the peak area. The RSD of the peak area of psoralen and isopsoralen is 0.8% and 0.9% (n = 6), respectively, indicating that the instrument precision is good.

[0045] Repeatability test Take 6 portions of the product of Example 2-7, prepare the test sample solution in parallel according to the method under item “3.2.2”, inject sample for determination and calculate the content. The average contents of psoralen and isopsoralen are 52.52 mg / mL and 67.28 mg / mL, respectively, and the RSDs are 1.5% and 1.7% (n = 6), respectively, indicating that the method has good repeatability.

[0046] Stability test Take the test sample solution of Example 1, inject sample for determination after being placed at room temperature for 0, 2, 4, 8, 12 and 24 h, respectively. The RSDs of the peak area of psoralen and isopsoralen are 1.3% and 1.6% (n = 6), respectively, indicating that the test sample solution has good stability within 24 h.

[0047] Spiked recovery test Precisely take 2.5 mL of the test sample with known content of Example 1, add a certain concentration of mixed control sample solution, prepare the solution and determine, and calculate the spiked recovery rate. The average recovery rates of psoralen and isopsoralen are 98.5% and 99.2%, respectively, and the RSDs are 1.2% and 1.5% (n = 6), respectively.

[0048] Sample content determination Take the sample of Example 1, prepare the sample solution, and determine under the chromatographic conditions. The content is calculated by external standard method. The results are shown in Table 1.

[0049] Table 1: Sample content determination results (n = 3, mg / mL)

[0050] Discussion Selection of chromatographic conditions In this experimental example, different mobile phase systems (such as methanol-water, acetonitrile-water, acetonitrile-different concentration of phosphoric acid / acetic acid aqueous solution) were compared. It was found that when acetonitrile-0.1% phosphoric acid aqueous solution (25:75) was used as the mobile phase, the target peak shape was symmetrical, the separation degree from the adjacent impurity peak was good, and the analysis time was moderate. The detection wavelength was determined by DAD full wavelength scanning, and 245 nm was the maximum absorption wavelength of psoralen and isopsoralen with the highest sensitivity.

[0051] Optimization of preparation of sample solution The effects of ultrasonic extraction and reflux extraction, as well as different solvents (methanol, ethanol) and different ultrasonic times on extraction efficiency were compared. The results showed that the effective components could be completely extracted by ultrasonic extraction with methanol for 30 minutes, and the operation was simple.

[0052] Results: Psoralen and isopsoralen had good linear relationships in the concentration ranges of 2.56 ~ 51.20 μg / mL (r = 0.9998) and 2.48 ~ 49.60 μg / mL (r = 0.9999), respectively. The average sample addition recovery rates were 98.5% and 99.2%, respectively, and the RSDs were 1.2% and 1.5% (n = 6), respectively.

[0053] Conclusion: This method is simple in operation, accurate in results, and good in repeatability, and can be used as an effective quality control method for the content determination of psoralen and isopsoralen in Yishen Yangyuan Heji.

Claims

1. A traditional Chinese medicine mixture having the effects of tonifying liver and kidney, characterized in that, The Chinese medicine mixture comprises the following components by weight: Radix Polygoni Multiflori 45-60; Rhizoma Polygonati 45-60; Rosa Laevigata 110-130; Angelica sinensis 2.4-3.2; Gynostemma pentaphyllum 45-60; Semen Euryale Ferox 3.2-3.8; Pericarpium Citri Reticulatae 1.8-2.4; Fructus Psoraleae 3.

5.

2. The Chinese medicine mixture according to claim 1, characterized in that, The Chinese medicine mixture comprises the following components by weight: Radix Polygoni Multiflori 52; Rhizoma Polygonati 52; Rosa Laevigata 121; Angelica sinensis 2.8; Gynostemma pentaphyllum 52; Semen Euryale Ferox 3.5; Pericarpium Citri Reticulatae 2.1; Fructus Psoraleae 3.

5.

3. The Chinese medicine mixture according to claim 1 or 2, characterized in that, The Chinese medicine mixture comprises the following components by weight: sucrose 150; sodium benzoate 1; talc 2.

4. The preparation method of the traditional Chinese medicine mixture according to claims 1-3, characterized in that, The method comprises the following steps: placing Radix Polygoni Multiflori, Rhizoma Polygonati, Rosa Laevigata, Angelica sinensis, Gynostemma pentaphyllum, Semen Euryale Ferox, Pericarpium Citri Reticulatae and Fructus Psoraleae in 3000 parts by weight of water and decocting for 1-2 hours, filtering, and reserving the filtrate; adding water to the residue to 3000 parts by weight, continuing to decoct for 1-2 hours, filtering, combining the filtrates, concentrating to a density of 1.10-1.16 g / mL, adding ethanol to an alcohol content of 60%, standing for 24 hours, taking the supernatant, filtering, and recovering the filtrate under reduced pressure to remove alcohol.

5. The production method according to claim 4, characterized by, After the filtrate is recovered under reduced pressure to remove alcohol, water is added to 120 parts by weight, talc 2 parts by weight and sodium benzoate 1 part by weight are added, and stirring is performed until uniform, and standing is performed for 24-48 hours.

6. The production method according to claim 5, wherein After standing for 24-48 hours, the upper clear liquid is taken, sucrose 120-150 parts by weight is added, water is added to 300-350 parts by weight, and stirring is performed until uniform.

7. The production method according to claim 6, characterized by, After stirring until uniform, boiling is performed, standing is performed, and filtering is performed, and the filtrate is the product mixture.

8. The preparation method according to claim 7, characterized in that, The sucrose is added in an amount of 150 parts by weight.

9. The preparation method according to claim 7, characterized in that, The water is added to an amount of 350 parts by weight.

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