Compound with effect of drastically draining water as well as preparation method and application of compound

Abstract

The invention discloses a compound with an effect of drastically draining water. The compound has a chemical structural formula as shown in a formula (I). The compound belongs to a novel tetracyclic triterpenoid natural product, has good fat solubility and chemical stability, and can be conveniently extracted from the rhizome of a herbal medicine Polygala fallax Hemsl. And prepared into an oral or injection form. The invention also provides a preparation method and application of the compound. The compound provided by the invention can obviously inhibit the increase of abdominal volume and ascites weight of mice, is in a dose-dependent relationship, and is a novel drainage medicine with great potential.

Description

Technical Field

[0001] The present invention belongs to the field of medicine and relates to a new medicinal tetracyclic triterpenoid natural product, and more specifically to the structure of salvia miltiorrhiza and its extraction method and application. Background Art

[0002] Ascites is the abnormal accumulation of fluid in the abdominal cavity due to various reasons. Its formation is a complex process involving multiple organs and systems. The main reasons are: cirrhosis leads to portal hypertension and hypoproteinemia, which is the most common cause of ascites; congestive heart failure, pericarditis, etc. lead to venous return obstruction, causing ascites; nephrotic syndrome leads to obstruction of water and excretion in the body, forming ascites; tumors such as ovarian cancer and colon cancer compress the lymphatic vessels, resulting in obstruction of lymphatic return and the formation of ascites; tuberculous peritonitis, inflammatory bowel disease, etc. lead to increased peritoneal vascular permeability, forming ascites; malnutrition, especially hypoproteinemia, leads to fluid leakage into the abdominal cavity, forming ascites; others include trauma, acute pancreatitis, connective tissue diseases, etc.

[0003] Ascites poses significant risks to patients in the following ways: 1. Direct physical effects: Ascites can cause abdominal distension and pain, and in severe cases, even dyspnea, impacting mobility and daily life. 2. Increased burden on the circulatory system: When ascites forms, the large amount of fluid that seeps into the peritoneal cavity causes hemoconcentration, a decrease in effective circulating blood volume, increased blood viscosity, and slowed blood flow, potentially leading to hypotension or shock. 3. Kidney damage: Ascites contains a large amount of nutrients and albumin. Excessive protein loss can exacerbate hypoproteinemia and further alter blood volume distribution in the circulatory system, damaging the kidneys. 4. Increased risk of infection: The presence of ascites can predispose to bacterial infection of the abdominal cavity, particularly during paracentesis or paracentesis, leading to secondary infection and peritonitis. 5. Additional burden on the liver: Ascites exacerbates liver ischemia and hypoxia, exacerbating hepatocyte necrosis. Particularly in patients with cirrhosis, the presence of ascites often indicates liver decompensation. 6. Other complications: Such complications as hepatic encephalopathy and bleeding from esophageal and gastric variceal veins can be life-threatening.

[0004] Prompt symptomatic treatment of ascites promotes drainage of accumulated fluid from the peritoneal cavity, alleviating patient pain and preventing complications, benefiting patient health. Currently, common treatments for ascites include salt restriction, sodium excretion, and diuresis. For refractory and tense ascites, drainage, albumin infusion, transjugular intrahepatic portosystemic shunts, and liver transplantation can be used; however, these approaches are not ideal. Traditional Chinese Medicine (TCM) emphasizes the principle of "drastic purgation to expel fluid." Classical herbs include Ginseng, Euphorbia, and Croton, which can rapidly expel accumulated fluid from the intestines, demonstrating significant clinical efficacy and distinctive TCM characteristics. However, the toxicity of these Euphorbiaceae herbs remains relatively high, and the active ingredients and mechanisms of their purgative properties remain unclear, worthy of further exploration.

[0005] Begonia limprichtii Irmscher is a perennial herb from the Begoniaceae family, a folk herbal medicine grown in southwestern my country. It is used to treat traumatic injuries, rheumatic pain, and sore throat with good safety. However, the chemical composition and drainage effects of this herb have not been reported. Summary of the Invention

[0006] One object of the present invention is to provide a small molecule compound with a novel structure and a strong purgative and water-removing effect as a new choice for ascites treatment in order to solve the above technical problems.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] In a first aspect, the present invention provides a compound having a purgative and water-expelling effect, which has a chemical structure as shown in formula (I):

[0009]

[0010] The compound, named cucurbitacin, contains 30 carbon atoms in its parent nucleus and is a typical tetracyclic triterpene compound. Its structural characteristic is that the anterior methyl group (19-CH3) is attached to C-9, rather than C-10, as is common in triterpenes. It also belongs to the cucurbitacin class. However, it lacks the hydroxyl group at C-16, as is common in cucurbitacins, making it a rare 16-dehydroxycucurbitacin with a novel structure that has not been reported before. The cucurbitacin monomer is a white powder that is poorly soluble in water but readily soluble in organic solvents such as methanol, ethanol, ethyl acetate, and chloroform. It has a bitter taste. Stability studies have shown that the product maintains its content and properties unchanged after 12 months at room temperature. Furthermore, under accelerated test conditions of 40°C and 75% relative humidity for 6 months, the product's physical and chemical properties show no significant changes. This indicates that its chemical properties are very stable, providing convenient conditions for the production, transportation, and storage of the preparation.

[0011] In a second aspect, the present invention provides a pharmaceutical composition comprising the compound of the present invention.

[0012] Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient.

[0013] In a third aspect, the present invention provides a method for preparing the compound of the present invention, comprising the following steps:

[0014] a. Take the dried rhizome of water lotus, crush it, extract it with an organic solvent, filter it, and concentrate it to obtain a fluid extract;

[0015] b. Add the fluid extract to water, stir, filter, wash with water, and dry to obtain a precipitate;

[0016] c. The precipitate was separated by silica gel column chromatography and eluted with a petroleum ether - ethyl acetate gradient;

[0017] d. Detect column chromatography fractions, combine, and concentrate to obtain the compound.

[0018] Preferably, the organic solvent in step a can be any one of organic solvents such as methanol, ethanol, ethyl acetate, acetone, chloroform, petroleum ether, or a mixed solvent thereof, such as a mixed solvent of petroleum ether and ethyl acetate (volume ratio 2:1), preferably methanol or ethanol of lower alcohols, more preferably medicinal alcohol, i.e., aqueous ethanol (such as aqueous ethanol with a volume fraction of 75%-85%), to comply with relevant regulations on pharmaceutical production, cost, safety, and environmental protection requirements. The extraction method can be percolation, reflux, maceration, microwave or supercritical extraction, preferably reflux.

[0019] The weight-to-volume ratio of water lily to the organic solvent is 1 g:3-5 mL, preferably 1 g:4 mL.

[0020] Preferably, step b is a water precipitation process, and the amount of water added is 5 to 15 times the weight of the extract, preferably 10 times, and stirred at room temperature or under heating to fully dissolve and suspend the paste, then cooled, allowed to stand, filtered, and the precipitate washed with clean water in small amounts multiple times.

[0021] Preferably, the column chromatography in step c can be repeated until the target product with the desired purity is obtained.

[0022] Preferably, in the step d, the column chromatography fraction is detected by thin layer chromatography or liquid chromatography.

[0023] More preferably, the thin layer chromatography is conventional silica gel thin layer, the developing solvent is petroleum ether-ethyl acetate (3:1) or chloroform-methanol (98:2); and the color development method is iodine fumigation.

[0024] More preferably, the liquid chromatography method uses a conventional C18 reverse phase silica gel chromatography column; the mobile phase is methanol-0.1% formic acid (50:50 to 100:0) gradient elution; and the detection wavelength is 237 nm.

[0025] The preparation method of the present invention has a short extraction route, simple operation, regenerable column chromatography filler, low cost, and feasibility of scaled-up production.

[0026] In a fourth aspect, the present invention provides use of the compound or pharmaceutical composition of the present invention in the preparation of a drug for draining ascites.

[0027] The results of the evaluation of the ascites-relieving effect of schizonepeta tenuifolia showed that the abdomen of mice inoculated with H22 mouse liver cancer cells was significantly enlarged, while the abdominal area of ​​mice inoculated with schizonepeta tenuifolia ... -1 ·d -1 ) can significantly inhibit the increase in abdominal volume and ascites weight of mice in a dose-dependent manner; at the same time, it was observed that the frequency of fecal discharge increased in the drug group mice, the stool was loose, and obvious diarrhea occurred, similar to "strong purgation to expel water".

[0028] Preferably, the compound is prepared into a pharmaceutically acceptable dosage form in the form of a monomer or a plant extract containing the compound.

[0029] Preferably, the dosage form comprises a pharmaceutically acceptable carrier and / or excipient.

[0030] The monomer of salvia miltiorrhiza or the plant extract containing salvia miltiorrhiza is made into a variety of pharmaceutically permitted dosage forms to meet the diverse needs of clinical medication. These dosage forms include tablets, hard capsules, soft capsules, granules, pills, ointments and injections. The pharmaceutically acceptable carriers, excipients or additives required for the preparations, specifically, diluents and absorbents commonly used in pharmacy, such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate, calcium hydrogen phosphate, light magnesium oxide, etc.; wetting agents and adhesives commonly used in pharmacy, such as water, glycerol, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, shellac, methylcellulose, potassium phosphate, polyvinyl pyrrolidone, etc.; disintegrants commonly used in pharmacy, such as dry starch, alginate, agar powder, brown algae starch, carbon Sodium bicarbonate, citric acid, calcium carbonate, polyoxyethylene, sorbitan fatty acid esters, sodium lauryl sulfate, methylcellulose, ethylcellulose, etc.; disintegration inhibitors, such as sucrose, tristearin, cocoa butter, hydrogenated oil, etc.; lubricants, such as talc, silicon dioxide, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, etc.; pharmaceutically commonly used cosolvents, such as ethanol, propylene glycol, polyethylene glycol, polysorbate 80, lecithin, urea, sodium benzoate, sodium salicylate, niacinamide, cyclodextrin, soybean oil, etc.; pharmaceutically acceptable carriers or excipients are not listed one by one, and those skilled in the art can make specific selections based on the common knowledge they possess.

[0031] Compared with existing ascites-relieving drugs, the scutellariae quinata of the present invention has the following benefits:

[0032] (1) Polypogonin is a new small molecule with a completely different structural type from existing drainage drugs, and may contain different targets and mechanisms of action;

[0033] (2) The effect of diaphoretic acid on ascites is similar to the traditional Chinese medicine method of "drafting to expel water", which promotes the rapid discharge of accumulated fluid from the intestines and has a significant therapeutic effect;

[0034] (3) The original plant has a long history of use as a folk herbal medicine and has no obvious toxic side effects, indicating that euphorbia pulex has good clinical safety;

[0035] (4) The original plant is a herbaceous plant of the genus Begonia (Begonia Linn.), which is similar to common begonia flower varieties in horticulture and can be artificially propagated and planted on a large scale to meet the demand for raw materials for large-scale production;

[0036] (5) The preparation process of scutellaria baicalensis is simple, and high-purity monomers can be obtained at low cost;

[0037] (6) Polypodium vulgare is highly lipophilic, well soluble, and easily absorbed orally;

[0038] (7) The physical and chemical properties of scutellaria baicalensis are stable and it has a long shelf life.

[0039] In conclusion, the scutellariae glutinosin of the present invention has a novel structure, outstanding advantages such as high efficiency, novel mechanism, stability, etc., and the raw materials are easily available and the cost is low. It is a new drug for expelling ascites with great development potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 This is the mass spectrum of euphorbia pulegone.

[0041] Figure 2 This is the H NMR spectrum of euphorbia cerifera.

[0042] Figure 3 This is the carbon NMR spectrum of euphorbia pulegone.

[0043] Figure 4 This is the liquid chromatogram of euphorbia pulegone.

[0044] Figure 5 This is the ultraviolet spectrum of euphorbia pulegone.

[0045] Figure 6 This is a diagram showing the efficacy of scutellaria baicalensis in treating ascites in mice, where A is a comparison of the appearance of mice; B is a comparison of the weight of mice; and C is a comparison of the abdominal circumference of mice. DETAILED DESCRIPTION

[0046] The technical solution of the present invention will be further described below in conjunction with the accompanying drawings and specific examples. Unless otherwise specified, the instruments or reagents used in the examples are conventional instruments or reagents in the art and are conventional products available on the market. Unless otherwise specified, the specific experimental procedures involved in the text are understood or known to those of ordinary skill in the art based on their common knowledge or conventional technical means, and will not be described in detail here.

[0047] Example 1: Extraction, separation and structure determination of euphorbia pulegone

[0048] 1. Example 1 of extraction and separation of euphorbia pulegonemin:

[0049] (1) 300 g of dried rhizomes of Begonia limprichtii Irmscher (purchased from the herbal medicine market in Leshan, Sichuan Province) were ground into coarse powder and placed in a round-bottom flask. 1.2 L of methanol was added and refluxed for 1 hour. The mixture was cooled and filtered. The residue was extracted twice more using the same method. The three extracts were combined and concentrated under reduced pressure to obtain 65 g of extract.

[0050] (2) Pour the extract into 650 mL of water, heat in a water bath at 80°C, and stir rapidly to fully dissolve, disperse, and suspend the paste. Then cool it, let it stand for 1 hour, filter it, wash the filter cake with a small amount of water several times, and dry it to obtain 33 g of precipitated powder.

[0051] (3) Take 20 g of the precipitated powder, dissolve it in 60 mL of methanol, mix it with silica gel, dry it, and load it into a silica gel column (silica gel specification 200-300 mesh). Use petroleum ether-ethyl acetate (10:0-0:10) gradient elution to receive 80 fractions (Fr1-80). Use silica gel thin layer to examine each fraction, develop it with petroleum ether-ethyl acetate (volume ratio 3:1), and color it with iodine fumigation. The results show that Fr15-Fr18 contain the same single main spot. Combine and concentrate to obtain 1.8 g of white powder (PSY-2).

[0052] The purity was determined by liquid chromatography. The chromatographic conditions were: ODS column (150×4.6, 5 μm), gradient elution of methanol-0.1% formic acid (50:50-100:0), detection wavelength of 237 nm, and flow rate of 1 mL / min.

[0053] The results are as follows Figure 4 As shown, the chromatogram showed a single major peak with a purity of >98%.

[0054] 2. Structure determination:

[0055] PSY-2 is a white powder. UVλmax:237、266(sh)nm( Figure 5 );ESI-TOF-MSm / z:541.3140[M+H] + ,558.3440[M+NH4] + ,563.3001[M+Na] + (Calculated value C 32 H 44 O7,540.308704)( Figure 1)。

[0056] 1 H-NMR(400MHz,CDCl3)δppm:1.03(3H,s,H-18),1.09(3H,s,H-19),1.15(3H,s,H-29),1.25(3H,s,H-28),1.36(3H,s,H-30),1.44(3H,s,H-21),1.54(3H,s,H-26),1.58(3H,s,H-27),2.03(3H,s,Ac),5.76(1H,m,H-6),5.94(1H,d,J=2.4Hz,H-1),6.41(1H,d,J=15.6Hz,H-23),7.12(1H,d,J=15.6Hz,H-24),3.49(1H,br s,H-10),3.13(1H,d,J=14.4Hz,H12b),2.74(1H,d,J=14.4Hz,H12a),2.33(1H,m,H-7a),2.03(1H,m,H-7b),2.04(1H,m,H-8),0.9~1.7(5H,m,H-15,16,17)( Figure 2 )。

[0057] 13 C-NMR(100MHz,CDCl3)δppm:114.98(C-1),144.49(C-2),198.76(C-3),47.50(C-4),136.65(C-5),120.94(C-6),23.54(C-7),41.56(C-8),48.85(C-9),34.77(C-10),213.54(C-11),48.63(C-12),50.32(C-13),48.30(C-14),34.08(C-15),20.92(C-16),49.04(C-17),18.98(C-18),19.94(C-19),78.81(C-20),23.97(C-21),201.58(C-22),118.90(C-23),153.33(C-24),79.07(C-25),26.73(C-26),25.94(C-27),27.98(C-28),20.19(C-29),17.58(C-30),21.89(Ac),169.78(Ac)( Figure 3 )。

[0058] With the help of HSQC, HMBC and other two-dimensional spectral analysis and reference to relevant literature (Magnetic Resonance In Chemistry 2005; 43: 489-491), the above spectral data were completely assigned, and PSY-2 was identified as a new cucurbitacin, named cucurbitacin.

[0059] The molecular formula of syringaphyllin (codename PSY-2) is C 32 H 44 O7 has a molecular weight of 540 and a molecular structure as shown in the following formula (I).

[0060]

[0061] The systematic name of the lycopodiol is (6R,E)-6-hydroxy-6-((9R,10R,13R,14S,17S)-2-hydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-4,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-methyl-5-oxohept-3-en-2-yl acetate ((6R,E)-6-hydroxy-6-( (9R,10R,13R,14S,17S)-2-hydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-4,7,8,9,10,11,12,13, 14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-methyl-5-oxohept-3-en-2-yl acetate).

[0062] 3. Example 2 of extraction and separation of euphorbia pulegonemin:

[0063] (1) Take 100 g of dried water lotus, grind it into coarse powder, put it into a round-bottom flask, add 500 mL of 80% v / v ethanol, reflux and extract for 1 hour, let it cool, and filter; extract the residue twice more in the same way; combine the three extracts and concentrate under reduced pressure to obtain 22 g of extract.

[0064] (2) Pour the extract into 330 mL of water, heat in a water bath at 80°C, and stir rapidly to fully dissolve, disperse, and suspend the paste. Then cool it, let it stand for 1 hour, filter it, wash the filter cake with a small amount of water several times, and dry it to obtain 13 g of precipitated powder.

[0065] (3) Take 10 g of the precipitated powder, dissolve it in 30 mL of methanol, mix it with silica gel, dry it, and load it into a silica gel column (silica gel specification 200-300 mesh), and use petroleum ether-ethyl acetate (10:0-0:10) gradient elution; examine each fraction with silica gel thin layer, develop it with petroleum ether-ethyl acetate (3:1), color it with iodine fumigation, guide it to be combined, and concentrate it to obtain 1.2 g of light yellow powder.

[0066] (4) The powder was dissolved in 5 ml of methanol, mixed with silica gel, dried, and loaded into a silica gel column (silica gel specification 200-300 mesh), and eluted with a gradient of petroleum ether-ethyl acetate (10:0-0:10); combined with silica gel thin layer guidance, concentrated to obtain 0.7 g of white powder.

[0067] 4. Example 3 of extraction and separation of euphorbia pulegonemin:

[0068] (1) Take 100 g of dried water lotus, grind it into coarse powder, put it into a round-bottom flask, add 300 mL of ethyl acetate, reflux and extract for 1 hour, let it cool, and filter; extract the residue twice in the same way; combine the three extracts and concentrate under reduced pressure to obtain 13 g of extract.

[0069] (2) Pour the extract into 65 mL of water, heat in a water bath at 80°C, and stir rapidly to fully dissolve, disperse, and suspend the paste. Then cool it, let it stand for 1 hour, filter it, wash the filter cake with a small amount of water several times, and dry it to obtain 11 g of precipitated powder.

[0070] (3) Take 10 g of the precipitated powder, dissolve it in 30 mL of methanol, mix it with silica gel, dry it, and load it into a silica gel column (silica gel specification 200-300 mesh), and use petroleum ether-ethyl acetate (10:0-0:10) gradient elution; examine each fraction with silica gel thin layer, develop it with petroleum ether-ethyl acetate (volume ratio 3:1), color it with iodine fumigation, combine it, and concentrate it to obtain 0.9 g of white powder.

[0071] 5. Example 4 of extraction and separation of euphorbia pulegonemin:

[0072] (1) Take 100 g of dried water lotus, grind it into coarse powder, put it into a round-bottom flask, add 350 mL of petroleum ether-ethyl acetate (volume ratio 2:1), reflux and extract for 1 hour, let it cool, and filter; extract the residue twice in the same way; combine the three extracts and concentrate under reduced pressure to obtain 12 g of extract.

[0073] (2) Pour the extract into 90 mL of water, heat in a water bath at 80°C, and stir rapidly to fully dissolve, disperse, and suspend the paste. Then cool it, let it stand for 1 hour, filter it, wash the filter cake with a small amount of water several times, and dry it to obtain 11 g of precipitated powder.

[0074] (3) Take 10 g of the precipitated powder, dissolve it in 30 mL of methanol, mix it with silica gel, dry it, and load it into a silica gel column (silica gel specification 200-300 mesh), and use petroleum ether-ethyl acetate (10:0-0:10) gradient elution; examine each fraction with silica gel thin layer, develop it with petroleum ether-ethyl acetate (volume ratio 3:1), color it with iodine fumigation, combine it, and concentrate it to obtain 1.0 g of white powder.

[0075] Chemical structure identification showed that the product obtained by the above extraction and separation examples 2-4 was identical to syringin (PSY-2).

[0076] Example 2: Pharmacological Effects of Polypogonin

[0077] 1. Experimental methods:

[0078] BALB / c mice were intraperitoneally injected with H22 mouse liver cancer cells (2×10 6 After 7 days, the ascites cells were collected and resuspended in PBS to a concentration of 2.67×10 7 Afterwards, each mouse was intraperitoneally injected with H22 cells (2×10 6 The mice inoculated with cells were gavaged with drugs (once a day) and the changes in the ascites volume of the mice were observed.

[0079] BALB / c mice were randomly divided into 5 groups:

[0080] (1) Normal group;

[0081] (2) Model group: H22;

[0082] (3) PSY-2 low-dose group: H22+PSY-2 (10 mg kg -1 ·d -1 );

[0083] (4) PSY-2 medium dose group: H22+PSY-2 (20 mg kg -1 ·d -1 );

[0084] (5) PSY-2 high-dose group: H22+PSY-2 (40 mg kg -1 ·d -1 ).

[0085] 2. Observation indicators:

[0086] Within 12 days, the body weight of the mice was measured and recorded, and the changes in the abdominal circumference of the mice were measured.

[0087] 3. Experimental results:

[0088] The abdomen of mice inoculated with H22 cells was significantly enlarged, while the enlargement of the abdomen of mice gavaged with PSY-2 was significantly suppressed ( Figure 6 , A), and showed a dose-dependent relationship.

[0089] At the same time, the changes in weight and abdominal circumference of mice measured also showed the same trend. The weight and abdominal circumference of mice inoculated with H22 cells increased significantly within 12 days, while the increase in weight and abdominal circumference of mice treated with PSY-2 drug was significantly inhibited ( Figure 6 , B, C).

[0090] At the same time, it was observed that the mice in the drug-treated group had obvious diarrhea, increased frequency of bowel movements, and loose stools, suggesting that ascites was mainly discharged through the intestines, which has the characteristics of "strong purgation to expel water" in traditional Chinese medicine.

[0091] Example 3: Preparation of scutellariae tablets

[0092] Take 50g of euphorbia pulex and a mixture of 1900g of lactose and starch (the weight ratio of lactose and starch is 3:2, filler) and place them in a mixing granulator. First, mix them at a low speed (about 100-200r / min) for 5-10 minutes to evenly disperse the active ingredient in the filler. Then, add 50mL of 5% mass concentration of hydroxypropyl methylcellulose (binder) aqueous solution, continue mixing at a medium speed (about 300-400r / min) for 10-15 minutes to make a soft material, granulate through an 80-mesh screen, dry to control the moisture content to 2%-5%, pass through a 100-mesh screen to granulate, and then fully mix with 40g of sodium carboxymethyl starch (disintegrant) and 10g of magnesium stearate (lubricant). Place the mixture in the hopper of a tablet press and press into 10,000 tablets, each containing 5mg of euphorbia pulex.

[0093] Example 4: Preparation of scutellaria baicalensis capsules

[0094] 50g of schisandrae alkaloids was placed in a mixer with 1800g of a mixture of microcrystalline cellulose and lactose (microcrystalline cellulose and lactose, weight ratio 2:1, filler) and mixed at 25 rpm for 10 minutes. 50mL of a 5% aqueous solution of hydroxypropyl methylcellulose (binder) was added and mixed for 15 minutes to form a soft material. The material was granulated through an 80-mesh sieve, dried to control the moisture content to 2%-5%, and granulated through a 100-mesh sieve. The material was then mixed with 50g of crospovidone (disintegrant) and 10g of magnesium stearate (lubricant) in a mixer and mixed at 20 rpm for 20 minutes. The mixture was then filled into capsules using a capsule filling machine to produce 10,000 capsules, each containing 5mg of schisandrae alkaloids.

[0095] Example 5: Preparation of scutellaria baicalensis injection

[0096] Place 50 g of nephrodiol in a clean container, add 5 L of PEG-400, stir to fully dissolve, dilute to 50 L with water for injection, filter through a 0.22 μm microporous membrane, and aseptically dispense the filtrate into 10,000 5 mL ampoules. Sterilize the sealed ampoules using moist heat sterilization at 121°C for 20 minutes. Each 5 mL ampoules contains 5 mg of nephrodiol.

[0097] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Therefore, any simple modifications, equivalent changes, and modifications to the above embodiments made in accordance with the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A compound having a strong diuretic effect, characterized in that: It has the chemical structure shown in formula (I):

2. A pharmaceutical composition, characterized in that The invention comprises the compound according to claim 1.

3. The pharmaceutical composition according to claim 2, characterized in that The pharmaceutical composition further includes a pharmaceutically acceptable carrier and / or excipient.

4. A method for preparing the compound according to claim 1, characterized in that: The following steps are involved: a. Take the dried rhizome of water lotus, crush it, extract it with an organic solvent, filter it, and concentrate it to obtain a fluid extract; b. Add the fluid extract to water, stir, filter, wash with water, and dry to obtain a precipitate; c. The precipitate was separated by silica gel column chromatography and eluted with a gradient of petroleum ether-ethyl acetate 10:0 to 0:10; d. Detect column chromatography fractions, combine, and concentrate to obtain the compound.

5. The method according to claim 4, characterized in that The organic solvent is any one or more of methanol, ethanol, ethyl acetate, acetone, chloroform, and petroleum ether.

6. The method according to claim 4, characterized in that The ratio of water lily to organic solvent is 1g:3-5mL.

7. The method according to claim 4, characterized in that In the step d, the column chromatography fraction is detected by thin layer chromatography or liquid chromatography.

8. Use of the compound according to claim 1 or the pharmaceutical composition according to claim 2 in the preparation of a drug for expelling ascites.

9. The use according to claim 8, characterized in that The compound is prepared into a pharmaceutically acceptable dosage form in the form of a monomer or a plant extract containing the compound.

10. The use according to claim 9, characterized in that The dosage form comprises a pharmaceutically acceptable carrier and / or excipient.

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