Use of morus alba extract in preparation of drug for treating and / or preventing prostate diseases

Abstract

The use of a Morus alba extract in the preparation of a drug for treating and / or preventing prostate diseases. The Morus alba extract contains an alkaloid with a weight content of 3% or more, and / or a polysaccharide with a weight content of no more than 70%, and / or a flavone with a weight content of no more than 10%, and / or an amino acid with a weight content of no more than 50%, and / or other components. The Morus alba extract has a significant therapeutic effect on prostate-related diseases.

Description

Use of mulberry extract in preparing medicine for treating and / or preventing prostate diseases Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to use of a mulberry extract in preparing a medicine for treating and / or preventing prostate diseases. Background Art

[0002] The human prostate is a hormone-dependent organ. Starting at around 40 years old, the transitional zone of the prostate begins to grow slowly at a rate of 1.6% per year, and this rate accelerates with age.

[0003] Benign prostatic hyperplasia (BPH), also known as benign prostatic hyperplasia (BPH), is a urological disease that commonly affects middle-aged and elderly men. Its primary manifestations are histological proliferation of prostatic stromal and glandular components, anatomical prostate enlargement, clinical symptoms primarily characterized by lower urinary tract symptoms, and urodynamic bladder outlet obstruction. Prostate volume enlargement occurs in over 50% of men over 50 years old, and in as many as 90% of men over 80 years old. The incidence of BPH continues to rise with the aging population. Numerous factors contribute to the development of BPH, including age, sex hormones, growth factors, and chronic inflammation. Sex hormone imbalance is the primary cause of BPH. Prostate growth depends on the synergistic effects of estrogen and androgen, and an imbalance in the estrogen-androgen ratio contributes to the development and progression of BPH. Clinically, medications used to treat BPH include α-blockers, 5α-reductase inhibitors, M receptor antagonists, phosphodiesterase 5 inhibitors, and β3-agonists.

[0004] Prostatitis refers to a prostate disease caused by a variety of complex factors, with urethral irritation and chronic pelvic pain as the primary clinical manifestations. Prostatitis is a common disease in urology, ranking first among male urology patients under 50 years old. Its overall prevalence in China is approximately 26.78%. Based on the prostatitis classification system established by the National Institutes of Health (NIH) in 1995, it is categorized into acute bacterial prostatitis (ABP), chronic bacterial prostatitis (CBP), chronic prostatitis (CP) / chronic pelvic pain syndrome (CPPS), and asymptomatic prostatitis. Nonbacterial prostatitis is far more common than bacterial prostatitis. CP / CPPS is the most common type of prostatitis in clinical practice, accounting for over 90% of chronic prostatitis cases. Clinically, it primarily presents with lower abdominal and perineal pain or pelvic discomfort, as well as lower urinary tract symptoms such as frequent urination, urgency, and pain. Some patients also experience psychological disturbances such as anxiety, depression, and fear, as well as sexual dysfunction such as erectile dysfunction and premature ejaculation. These symptoms severely impact patients' physical and mental health and quality of life, while also increasing the socioeconomic burden. Currently, medications used to treat prostatitis include alpha-blockers, antibiotics, and nonsteroidal anti-inflammatory drugs.

[0005] Benign prostatic hyperplasia (BPH) and prostatitis not only seriously endanger patients' physical health but also their mental health. Treatments primarily rely on Western medicine, which primarily aims to alleviate symptoms. These medicines are associated with numerous adverse reactions, lack specificity, and offer suboptimal long-term efficacy. Therefore, it is imperative to identify treatments for prostate disease with minimal side effects and a favorable prognosis. Summary of the Invention

[0006] The present invention provides a method for treating and / or preventing prostate diseases, comprising administering a therapeutically or prophylactically effective amount of the mulberry extract to a patient in need thereof. The mulberry extract has a significant therapeutic effect on prostate-related diseases.

[0007] In the present invention, based on the weight percentage of the sum of the components of the mulberry extract as 100%, the mulberry extract contains 3% or more of alkaloids by weight (optionally containing 3-99% of alkaloids by weight, further optionally containing 15-99% of alkaloids by weight, further optionally containing 30-99% of alkaloids by weight, further optionally containing 40-99% of alkaloids by weight, further optionally containing 50-99% of alkaloids by weight, further optionally containing 60-99% of alkaloids by weight),

[0008] and / or contains no more than 70% polysaccharide by weight (optionally containing 0.2-70% polysaccharide by weight, further optionally containing 0.2-50% polysaccharide by weight, further optionally containing 0.2-35% polysaccharide by weight, further optionally containing 0.2-25% polysaccharide by weight, further optionally containing 0.2-23% polysaccharide by weight, further optionally containing 20-25% polysaccharide by weight),

[0009] and / or contains flavonoids in an amount not higher than 10% by weight (optionally containing flavonoids in an amount of 0.05-5% by weight, further optionally containing flavonoids in an amount of 0-2% by weight, further optionally containing flavonoids in an amount of 0.05-2% by weight, further optionally containing flavonoids in an amount of 0.5-1.5% by weight, further optionally containing flavonoids in an amount of 0-1% by weight, further optionally containing flavonoids in an amount of 0.05-1% by weight),

[0010] and / or contains no more than 50% by weight of amino acids (optionally containing 0-30% by weight of amino acids, further optionally containing 0-25% by weight of amino acids, further optionally containing 0-20% by weight of amino acids, further optionally containing 0-5% by weight of amino acids, further optionally containing 3-25% by weight of amino acids or further optionally containing 5-20% by weight of amino acids),

[0011] and / or other components (the weight content can be optionally 0-25%, further optionally 0-20%, further optionally 0-15%, further optionally 0-11%, further optionally 2-20%, further optionally 4-8%).

[0012] Optionally, the prostate disease includes at least one of prostatitis and prostatic hyperplasia;

[0013] Optionally, the prostatitis includes at least one of acute bacterial prostatitis, chronic bacterial prostatitis, chronic non-bacterial prostatitis, chronic pelvic pain syndrome, and asymptomatic prostatitis;

[0014] Optionally, the symptoms of chronic prostatitis include lower abdominal, perineal pain or pelvic discomfort, which may be accompanied by urinary frequency, urgency, pain, urinary tract obstruction, sexual dysfunction, or depression symptoms;

[0015] Optionally, the treatment and / or prevention of prostatic hyperplasia is manifested by at least one of the following:

[0016] 1) Reduce prostate-specific antigen (PSA) levels;

[0017] 2) Alleviate pathological damage to prostate tissue;

[0018] 3) Inhibit the proliferation of prostate hyperplasia cells;

[0019] Optionally, the treatment and / or prevention of prostatitis is characterized by at least one of the following:

[0020] (1) Alleviate the pathological damage of the patient's prostate tissue;

[0021] (2) Reduce prostate-specific antigen (PSA) levels.

[0022] In one embodiment, the alleviation of prostate tissue pathological damage is manifested as any one of the following: prostate luminal epithelial cells are single-layered and cubical, the glandular cavity is enlarged, the tissue structure is relatively clear, or the infiltration of inflammatory cells in the glandular interstitium is reduced.

[0023] In one embodiment, the prostate disease is caused by a high-fat diet and / or obesity.

[0024] In another aspect, the present invention provides a use of mulberry extract, which is at least one of the following (a1) to (a3):

[0025] (a1) Use in the preparation of a medicament for reducing prostate-specific antigen (PSA) content;

[0026] (a2) Use in the preparation of a medicament for alleviating pathological damage to prostate tissue;

[0027] (a3) Use in the preparation of a medicament for inhibiting the proliferation of prostate hyperplasia cells.

[0028] In another aspect, the present invention provides a use of mulberry extract, which is at least one of the following (b1) to (b3):

[0029] (a1) Use for lowering prostate-specific antigen (PSA);

[0030] (a2) Use in alleviating pathological damage to prostate tissue;

[0031] (a3) Use in inhibiting the proliferation of prostate hyperplasia cells.

[0032] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0033] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0034] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0035] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0036] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0037] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0038] Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are:

[0039] Further optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight contents of the components in the mulberry extract are:

[0040] Further optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight contents of the components in the mulberry extract are:

[0041] Optionally, based on the mulberry extract, the weight content of each component is:

[0042] Optionally, based on the mulberry extract, the weight content of each component is:

[0043] Optionally, based on the mulberry extract, the weight content of each component is:

[0044] Optionally, based on the mulberry extract, the weight content of each component is:

[0045] Optionally, based on the mulberry extract, the weight content of each component is:

[0046] Optionally, based on the mulberry extract, the weight content of each component is:

[0047] Optionally, based on the mulberry extract, the weight content of each component is:

[0048] The weight content of each component in the mulberry extract is:

[0049] More preferably, the alkaloids include 1-deoxynojirimycin (DNJ), N-methyl-1-deoxynojirimycin (N-methly-1-deoxynojirimycin), fagomine (FAG), 3-epi-fagomine, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), calystegin B2, calystegin C1, 2-oxy-(α- One or more of 2-O-(α-D-galactopyranosyl)-1-deoxynojirimycin, 6-O-(β-D-glucopyranosyl)-1-deoxynojirimycin, and 1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol;

[0050] Optionally, the weight percentage of DNJ is not less than 50% (optionally 60-99%) of the total alkaloids.

[0051] Optionally, the heavy metal content of the mulberry extract does not exceed 10 ppm.

[0052] Optionally, the mulberry extract is administered to humans or mammals.

[0053] Optionally, the drug is in an oral dosage form.

[0054] Optionally, the drug is in the form of tablets, capsules, oral solutions, oral emulsions, pills, granules, syrups or powders.

[0055] In the present invention, the mulberry extract can be provided in the form of commercially available Morus alkaline tablets (National Medicine Standard No. Z20200002).

[0056] Alternatively, the mulberry extract can be prepared according to the method described in CN 110393738A. In one embodiment, the preparation of the mulberry extract comprises the following steps: preparing a crude extract of a moraceae plant; optionally, separating the extract with a cationic resin and / or an anionic resin; optionally, subjecting the resin effluent to alcohol precipitation and collecting the supernatant; and optionally, concentrating and / or drying the supernatant.

[0057] Optionally, in the present invention, the preparation of the mulberry extract comprises the following steps: 1) preparing a crude extract of a moraceae plant; 2) separating the crude extract through a cationic resin and / or an optional anionic resin to obtain a resin effluent; and optionally, step 3) subjecting the resin effluent of step 2) to alcohol precipitation and collecting the supernatant; and 4) concentrating and / or drying the supernatant. Optionally, the resin effluent of step 2) may be concentrated and / or dried before being subjected to alcohol precipitation.

[0058] Optionally, the plant of the Moraceae family is Morus multicaulis Perrott., Morus alba L., Morus atropurpurea Roxb., Morus mizuho Hotta, Morus wittiorum Hand Mazz., Morus laevigata Wall, Morus nigra Linn., Morus cathayana Hemsi., Morus serrata Roxb., Morus mongolica Schneid., Morus bombycis Koidz., Morus notabilis Schneid., Morus nigriformis Koidz., Morus yunnanensis Koidz., Morus australis Poir., Morus mongolica (Bur.) Schneid var. diabolica Koidz.), Morus alba Var. Pendula Dippel, Morus alba Var. Pendula Dippel, Morus alba, and mulberry varieties bred from the above mulberry species, or a combination of one or more of the following:

[0059] Optionally, the moraceae plant is one or more selected from the group consisting of Guangdong mulberry, Shandong mulberry, white mulberry, fine-toothed mulberry, mountain mulberry, or hybrid mulberry, and the hybrid mulberry can be Yuesang No. 11, Guisang You No. 62, or Sang Te You No. 2. Any part of the moraceae plant, including leaves, roots, branches, bark, buds, stems, and fruits, can be used, and mulberry branches, mulberry leaves, or white mulberry bark can be used.

[0060] In the present invention, the mulberry extract can be selected from mulberry branch extract, white mulberry bark extract, mulberry leaf extract or a mixed extract thereof.

[0061] In one embodiment, the mulberry extract is prepared according to the following steps: crushing the moraceae plant, heating and refluxing the extract with water and / or alcohol solution or acid water, the amount of solvent is 3-20 times that of the original medicinal material, repeating the extraction 1-3 times, combining the extracts, concentrating, applying a cation exchange resin, eluting with 0.2-3N ammonia water, applying the eluate to an anion exchange resin, collecting the non-adsorbed portion, adding ethanol, precipitating to remove impurities, concentrating and / or drying to obtain the extract.

[0062] In one embodiment, the mulberry extract is prepared according to the following steps: crushing the moraceae plant, heating and refluxing the extract with water and / or alcohol solution or acid water, the amount of solvent is 3-20 times that of the original medicinal material, repeating the extraction 1-3 times, combining the extracts, concentrating, applying a cation exchange resin, eluting with 0.2-3N ammonia water, applying the eluate to an anion exchange resin, collecting the non-adsorbed portion, concentrating and / or drying to obtain the extract.

[0063] In one embodiment, the mulberry extract is prepared according to the following steps: crushing the moraceae plant, heating and refluxing the extract with water and / or alcohol solution or acid water, the amount of solvent is 3-20 times that of the original medicinal material, repeating the extraction 1-3 times, combining the extracts, concentrating, applying a cation exchange resin, eluting with 0.2-3N ammonia water, concentrating and / or drying the eluate to obtain the extract.

[0064] In one embodiment, the mulberry extract is prepared according to the following steps: crushing the moraceae plant, heating and refluxing the extract with water, the amount of solvent is 3-20 times (optionally 4-15 times, further optionally 4-12 times) of the original medicinal material, repeating the extraction 1-3 times (the extraction time can be 0.5-3 hours each time, further optionally 1-2 hours each time), combining the extracts, concentrating, applying a cation exchange resin, eluting with 0.2-3N ammonia water, applying the eluate to an anion exchange resin, collecting the non-adsorbed portion (i.e., the anion resin effluent), adding ethanol, precipitating to remove impurities, concentrating and / or drying to obtain an extract.

[0065] Optionally, the crude extract after the concentration treatment can also be subjected to alcohol precipitation treatment before the resin separation treatment in step 2). During the alcohol precipitation treatment, ethanol is added to the crude extract, stirred and mixed, and the stirring is stopped and allowed to stand for a certain time to precipitate the insoluble matter therein. Optionally, the volume mass ratio of the added ethanol to the plant raw material is 0.2-20 times, optionally 0.4-10 times, in terms of L / kg. Further optionally, an alcohol precipitation tank is used for alcohol precipitation treatment. Optionally, the stirring speed in the alcohol precipitation treatment is 10-600rpm, optionally 40-500rpm, further optionally 80-400rpm or 300rpm.

[0066] Optionally, after the cationic resin is loaded into the column, it is activated in the order of washing with an acidic solution, washing with an alkaline solution, and washing with an acidic solution. Optionally, the alkaline solution is washed until the pH of the eluate is 8.0-9.5, optionally 8.5-9.5; optionally, the alkaline solution is selected from aqueous ammonia solution, sodium hydroxide solution, potassium hydroxide solution, or sodium carbonate solution; optionally, the concentration of the alkaline solution is 0.5-4 mol / L, optionally 1-2 mol / L. Optionally, the acidic solution is washed until the pH of the eluate is 3.0-7.0, optionally 4.5-6.5. Optionally, the acidic solution is selected from hydrochloric acid solution, phosphoric acid solution, or sodium hydrogen phosphate-citrate buffer; optionally, the concentration of the acidic solution is 0.5-4 mol / L, optionally 1.5-2 mol / L. Optionally, after the final acidic solution wash, the cationic resin can be rinsed with 3-5 column volumes of deionized water.

[0067] Optionally, the cationic resin is a combination of one or more of 732 strong acid styrene cation exchange resin, 002SC strong acid styrene cation exchange resin, 734 strong acid styrene cation exchange resin, D001 macroporous strong acid styrene cation exchange resin or D113 macroporous weak acid cation exchange resin and D254 macroporous strong basic quaternary ammonium cation exchange resin.

[0068] Optionally, the weight ratio of the cationic resin to the plant raw material is 1:1-30 (optionally, 1:1-25, 1:2-20, 1:2-15, 1:2-10, 1:2-7, 1:2-3).

[0069] After the crude plant extract is loaded onto the cationic resin, the loaded cationic resin is eluted with an eluent. Optionally, the eluent is a salt solution or alkaline solution containing cations, and can be selected from one or more of sodium chloride, ammonium chloride, ammonium sulfate, ammonium nitrate, ammonia water, potassium chloride, and sodium hydroxide.

[0070] Optionally, the concentration of the eluent is 0.04-5 mol / L (optionally 0.5-2.5 mol / L, 0.2-3 mol / L, further optionally 0.5-2.5 mol / L).

[0071] Optionally, the eluent flow rate is 1-15 BV / h (optionally 5-10 BV / h, further optionally 5-6 BV / h).

[0072] Optionally, the weight of the eluent used for cationic resin separation is 0.1-30 times the weight of the plant raw material, and optionally, the eluent is 0.5-10 times the weight of the plant raw material.

[0073] The collection starting point can be determined according to the pH of the cationic resin effluent. For example, when an alkaline solution such as aqueous ammonia is used for elution, the eluate is collected when the pH of the cationic column effluent is detected to be greater than 7, or the collection starting point of the effluent is determined based on a color development or precipitation reaction. Optionally, when the volume of the collected liquid reaches 0.1-10 times (further optionally, 0.2-5 times) the weight of the plant raw material fed, collection is stopped, and the collected liquid is optionally purified by an anion column.

[0074] When purifying by anion column, optionally, after the anion resin is loaded into the column, activation is performed in the order of washing with alkaline solution, washing with acidic solution, and washing with alkaline solution.

[0075] Optionally, washing with an alkaline solution until the pH of the eluate is 8.0-9.5, optionally 8.5-9.5;

[0076] Optionally, the alkaline solution is selected from ammonia solution, sodium hydroxide solution, potassium hydroxide solution or sodium carbonate solution; optionally, the concentration of the alkaline solution is 0.5-4 mol / L, optionally 1-2 mol / L.

[0077] Optionally, the acidic solution is washed until the pH of the eluate is 3.0-7.0, optionally 4.5-6.5. Optionally, the acidic solution is selected from hydrochloric acid solution, phosphoric acid solution, disodium hydrogen phosphate-citric acid buffer, and optionally, the concentration of the acidic solution is 0.5-4 mol / L, optionally 1-2 mol / L.

[0078] Optionally, the anion resin is a combination of one or more of 711 type strong basic styrene anion resin, 717 type strong basic styrene anion exchange resin, D201 type macroporous strong basic styrene anion exchange resin or D218 type macroporous strong basic acrylic anion exchange resin, D301-G type macroporous weak acid styrene anion exchange resin and D301 type macroporous weak basic styrene anion exchange resin.

[0079] Optionally, the weight ratio of the anion resin to the plant raw material is 1:1-80 (optionally, 1:1-64, 1:1-32, 1:1-24, 1:5-16, 1:3).

[0080] When the liquid flows out of the anion resin, collection begins. Optionally, collection is stopped when the volume of the collected liquid reaches 0.05-10 times (optionally, 0.1-5 times) the weight of the plant raw material input.

[0081] Optionally, the weight ratio of ethanol used in the alcohol precipitation treatment to the plant raw material is 1:4-600 (optionally 1:20-300, further optionally 1:20-50, 1:40, 1:80, 1:22). During the alcohol precipitation treatment, the stirring speed is 10-600 rpm (optionally 40-500 rpm, 80-400 rpm). The alcohol precipitation treatment time is 12-24 hours.

[0082] Furthermore, before the alcohol precipitation treatment, the anion resin effluent is subjected to a step of centrifugal impurity removal or microfiltration membrane filtration, followed by concentration by a reverse ion osmosis membrane. The specific gravity of the concentrated liquid can be 1.0-1.3, optionally 1.1-1.25.

[0083] Optionally, the drug further comprises a pharmaceutically acceptable carrier. The carrier is an inactive ingredient that is non-toxic to the human body and is consistent with the route of administration or mode of administration. The carrier can be a solid or liquid excipient. Solid excipients include, for example, microcrystalline cellulose, mannitol, lactose, pregelatinized starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, aspartame, calcium hydrogen phosphate, sodium lactate, poloxamer, sodium lauryl sulfate, sodium carboxymethyl cellulose, gelatin, xanthan gum, povidone, starch, magnesium stearate, sodium carboxymethyl starch, and talc; liquid excipients include, for example, water, ethanol, syrup, and glycerol.

[0084] In the present invention, the mulberry extract is referred to as SZ-A. Beneficial effects:

[0085] The mulberry extract of the present invention can reduce PSA in obese mice, alleviate prostate tissue pathological damage, improve prostate tissue morphology, and improve inflammation levels. In short, the mulberry extract can improve prostate-related diseases, including prostatic hyperplasia and prostatitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0086] Figure 1 shows the effect of the mulberry extract in Experimental Example 1 on serum PSA in a HFD-induced obese C57BL / 6 mouse model;

[0087] FIG2 shows the effect of the mulberry extract in Experimental Example 1 on prostate tissue pathology in the HFD diet-induced C57BL / 6 obese mouse model.

[0088] FIG3 is a bar graph showing the results of BPH-1 cell activity in experimental groups A1-A4 in Experimental Example 2.

[0089] FIG4 is a bar graph showing the results of BPH-1 cell activity in experimental groups B1-B4 in Experimental Example 2. DETAILED DESCRIPTION

[0090] Preparation Example 1 of Mulberry Extract

[0091] 1000 kg of fresh mulberry branches (fine-toothed mulberry, Yuesang No. 11) were crushed and added to 4000 L of water. The extracts were then heated and refluxed for 2 hours. The combined extracts were filtered to remove insoluble matter to obtain a crude extract. The crude extract was heat-concentrated to a solids content of 4% by weight and then heated to 50°C to serve as the loading solution for a cationic resin column.

[0092] A 150 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide until the eluate pH reached 8.5; and finally with 2 mol / L hydrochloric acid until the eluate pH reached 4.5. The column was then rinsed with 5 column volumes of deionized water to complete activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was >7. When the collected solution reached 900 L, the collection was stopped and the collected solution was directly passed through an anion column for purification.

[0093] Activate the column using 62.5 kg of D218 macroporous, strongly basic acrylic anion resin. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. Elute with 1.5 mol / L hydrochloric acid solution until the eluate has a pH of 3.5. Finally, elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. The collected eluate from the cationic resin is loaded onto the anionic resin, and the effluent is collected until 920 L of effluent is reached.

[0094] The collected liquid was centrifuged to remove impurities and then concentrated using a reverse ion osmosis membrane. The concentrated liquid had a specific gravity of 1.25 and was transferred to an alcohol precipitation tank. 25 L of anhydrous ethanol was added with a stirring paddle at 500 rpm. After the ethanol addition was complete, stirring was stopped and the mixture was allowed to settle for 24 hours. The supernatant was collected and concentrated under reduced pressure to obtain a mulberry branch extract (i.e., mulberry extract SZ-A).

[0095] The mulberry branch extract contains 52% by weight of alkaloids, 22% by weight of polysaccharides, 0.8% by weight of flavonoids, and 20% by weight of amino acids. Among the alkaloids, the content of 1-DNJ is 60%, FAG is 17%, and DAB is 15%.

[0096] Preparation Example 2 of Mulberry Extract

[0097] Take 10kg of fresh mulberry branches (Sang Teyou No. 2), crush them, add 150L of water, add them twice, extract them by decoction for 3h each time, combine the extracts, and filter to remove insoluble matter. The extract is hot concentrated until the solid content reaches 8%, then transferred to an alcohol precipitation tank, and 2367.9g of absolute ethanol (3L) is added under a stirring paddle at 300rpm. After the ethanol addition is complete, stop stirring, precipitate with alcohol for 24h, and take the supernatant as the loading liquid for a cationic resin column. Use 5kg of 002SC type strong acid styrene cationic resin to fill the column, and activate the cationic resin according to the method of Preparation Example 1. Load the extract after concentrated alcohol precipitation, then use 100L of 5mol / L potassium chloride to elute, with an elution rate of 5BV / h, and detect the effluent with 20% silicotungstic acid. Start collecting when a white precipitate is generated. Stop collecting when the collected liquid reaches 25L, and the collected liquid is directly purified by anion column.

[0098] A 10 kg column of 711 strong base styrene anion resin was loaded and activated according to the method of Preparation Example 1. The collected cationic resin eluate was loaded onto the anion resin, and the effluent was collected until the effluent reached 15 L. The collected eluate was reloaded onto the cationic resin and separated twice more using the cationic resin and anion resin, respectively, according to the above method.

[0099] The collected liquid obtained after three column separations was centrifuged for impurity removal and then concentrated using a reverse ion osmosis membrane. The concentrated liquid had a specific gravity of 1.25 and was transferred to an alcohol precipitation tank. 125 g of anhydrous ethanol was added under a stirring paddle at 1000 rpm. After the ethanol addition was complete, stirring was stopped and the mixture was allowed to precipitate with alcohol for 24 hours. The supernatant was then collected and concentrated under reduced pressure to obtain an extract. Separately, fresh Morus alba bark and mulberry leaf (Sang Teyou No. 2) were extracted using the same extraction method and parameters as described above.

[0100] The obtained mulberry branch extract has an alkaloid content of 98%, a polysaccharide content of 0.2%, a flavonoid content of 0.05%, and an amino acid content of 0. Among the alkaloids, the content of 1-DNJ is 99%, FAG is 0.5%, and DAB is 0.4%.

[0101] The obtained Morus alba bark extract contains 95% alkaloids, 2% polysaccharides, 0.1% flavonoids, and 1% amino acids. Among the alkaloids, the content of 1-DNJ is 96%, FAG is 1.5%, and DAB is 1.4%.

[0102] The mulberry leaf extract contains 90% alkaloids, 4% polysaccharides, 0.1% flavonoids, and 3% amino acids. Among the alkaloids, the content of 1-DNJ is 91%, FAG is 3.1%, and DAB is 2.8%.

[0103] Preparation Example 3 of Mulberry Extract

[0104] 1000 kg of fresh mulberry branches (Mulberry twigs) were crushed, added to 11,500 L of water, and heated under reflux for 2 hours. The extracts were combined and filtered to remove insoluble matter to obtain a crude extract. This crude extract was first centrifuged to remove impurities and then concentrated using a counter-ion permeation membrane to a solids content of 1% by weight. This was then used as the loading solution for the cationic resin column.

[0105] A column was loaded with 300 kg of D001 macroporous, strongly acidic styrene-based cationic resin, which was activated according to the method of Preparation Example 1. The concentrated crude extract was loaded and eluted with 5000 L of 0.04 mol / L ammonium nitrate at a rate of 5 BV / h. The effluent was tested with 20% silicotungstic acid. Collection began when a white precipitate formed and stopped when the collected solution reached 1000 L.

[0106] The collected liquid obtained after the cationic column separation is concentrated by nanofiltration membrane and concentrated under reduced pressure to obtain an extract concentrate.

[0107] The obtained mulberry branch extract has an alkaloid content of 15%, a polysaccharide content of 20%, a flavonoid content of 7%, and an amino acid content of 45%. Among the alkaloids, the content of 1-DNJ is 55%, FAG is 23%, and DAB is 10%.

[0108] Preparation Example 4 of Mulberry Extract

[0109] Take 333 kg of dry mulberry branches (Yue Sang No. 11), crush them, add 4000 L of water, and extract them twice by heating reflux method, each time reflux for 1 hour, combine the extracts, filter, and concentrate the extracts to 1 kg of crude drug / L.

[0110] A 150 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide until the eluate pH reached 8.5; and finally with 2 mol / L hydrochloric acid until the eluate pH reached 4.5. The column was then rinsed with 5 column volumes of deionized water to complete activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was >7. When the collected solution reached 900 L, the collection was stopped and the collected solution was directly passed through an anion column for purification.

[0111] Activate the column using 125 kg of D218 macroporous, strongly basic acrylic anion resin. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. Elute with 1.5 mol / L hydrochloric acid solution until the eluate has a pH of 3.5. Finally, elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. The collected cationic resin eluate is loaded onto the anion resin, and the effluent with a pH greater than 8 is collected until the effluent reaches 870 L.

[0112] The collected liquid after anion column separation was filtered through a microfiltration membrane to remove impurities and then concentrated using a counter-ion osmosis membrane. The concentrated liquid had a specific gravity of 1.1 and was transferred to an alcohol precipitation tank. 15 kg of anhydrous ethanol was added with a stirring paddle at 400 rpm. Stirring was stopped after the ethanol addition, and the mixture was allowed to settle for 24 hours. The supernatant was collected and concentrated under reduced pressure to obtain a mulberry branch extract. The sample contained 80% alkaloids by weight, 5% polysaccharides by weight, 0.1% flavonoids by weight, and 4% amino acids by weight. Among the alkaloids, 1-DNJ accounted for 75%, FAG for 12%, and DAB for 10%.

[0113] Preparation Example 5 of Mulberry Extract

[0114] Take 400 kg of dry mulberry branches (Yue Sang No. 11), crush them, add 4000 L of water, and extract them twice by heating reflux method, each time reflux for 1 hour, combine the extracts, filter, and concentrate the extracts to 1 kg of crude drug / L.

[0115] Activate the column using 62.5 kg of D218 macroporous, strongly basic acrylic anion resin. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0; then with 1.5 mol / L hydrochloric acid solution until the eluate has a pH of 3.5; and finally with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. The collected extract concentrate was loaded onto the anion resin, and the effluent was collected.

[0116] The collected solution after anion column separation was filtered through a microfiltration membrane to remove impurities, then concentrated using a counter-ion permeation membrane. Further vacuum concentration and drying yielded a mulberry twig extract. The sample contained 3% by weight of alkaloids, 70% by weight of polysaccharides, 10% by weight of flavonoids, and 10% by weight of amino acids. Among the alkaloids, the content of 1-DNJ was 68%, FAG was 17%, and DAB was 8%.

[0117] Preparation Example 6 of Mulberry Extract

[0118] 1500 kg of fresh mulberry branches (fine-toothed mulberry, Yuesang No. 11) were crushed and added to 6000 L of water. The extracts were heated and refluxed for 2 hours. The combined extracts were filtered to remove insoluble matter to obtain a crude extract. The crude extract was heat-concentrated to a solids content of 4% by weight and then heated to 50°C as the loading solution for a cationic resin column.

[0119] A 100 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide until the eluate pH reached 8.5; and finally with 2 mol / L hydrochloric acid until the eluate pH reached 4.5. The column was then rinsed with 5 column volumes of deionized water to complete activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was >7. When the collected solution reached 900 L, the collection was stopped and the collected solution was directly passed through an anion column for purification.

[0120] A column was loaded with 62.5 kg of D218 macroporous, strongly alkaline acrylic anion resin. The column was washed with a 1.5 mol / L sodium hydroxide solution until the eluate had a pH of 9.0; then washed with a 1.5 mol / L hydrochloric acid solution until the eluate had a pH of 3.5; and finally washed with a 1.5 mol / L sodium hydroxide solution until the eluate had a pH of 9.0. Activation was completed. The collected cationic resin eluate was loaded onto an anionic resin, and the effluent was collected until the effluent reached 870 L. The effluent was concentrated under reduced pressure to obtain a mulberry branch extract concentrate, which contained 30% by weight alkaloids, 35% by weight polysaccharides, 2% by weight flavonoids, and 25% by weight amino acids. Among the alkaloids, the content of 1-DNJ was 62%, FAG was 20%, and DAB was 13%.

[0121] Preparation Example 7 of Mulberry Extract

[0122] 1000 kg of fresh mulberry branches (fine-toothed mulberry, Yuesang No. 11) were crushed and added to 4000 L of water. The extracts were then heated and refluxed for 2 hours. The combined extracts were filtered to remove insoluble matter to obtain a crude extract. The crude extract was heat-concentrated to a solids content of 4% by weight and then heated to 50°C to serve as the loading solution for a cationic resin column.

[0123] A 100 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide until the eluate pH reached 8.5; and finally with 2 mol / L hydrochloric acid until the eluate pH reached 4.5. The column was then rinsed with 5 column volumes of deionized water to complete activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was >7. When the collected solution reached 900 L, the collection was stopped and the collected solution was directly passed through an anion column for purification.

[0124] A 62.5 kg column of D218 macroporous, strongly alkaline acrylic anion resin was loaded and washed with a 1.5 mol / L sodium hydroxide solution until the eluate had a pH of 9.0; then with a 1.5 mol / L hydrochloric acid solution until the eluate had a pH of 3.5; and finally with a 1.5 mol / L sodium hydroxide solution until the eluate had a pH of 9.0. Activation was completed. The collected cationic resin eluate was loaded onto an anionic resin, and the effluent was collected until the effluent reached 870 L. The effluent was concentrated under reduced pressure to obtain a mulberry branch extract concentrate, which contained 40% by weight alkaloids, 25% by weight polysaccharides, 0.5% by weight flavonoids, and 25% by weight amino acids. Among the alkaloids, the content of 1-DNJ was 57%, FAG was 24%, and DAB was 16%.

[0125] Preparation Example 8 of Mulberry Extract

[0126] Take 333 kg of dry mulberry branches (Yue Sang No. 11), crush them, add 4000 L of water, and extract them twice by heating reflux method, each time reflux for 1 hour, combine the extracts, filter, and concentrate the extracts to 1 kg of crude drug / L.

[0127] A 150 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide until the eluate pH reached 8.5; and finally with 2 mol / L hydrochloric acid until the eluate pH reached 4.5. The column was then rinsed with 5 column volumes of deionized water to complete activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was >7. When the collected solution reached 900 L, the collection was stopped and the collected solution was directly passed through an anion column for purification.

[0128] Activate the column using 62.5 kg of D218 macroporous, strongly basic acrylic anion resin. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. Elute with 1.5 mol / L hydrochloric acid solution until the eluate has a pH of 3.5. Finally, elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. The collected cationic resin eluate is loaded onto the anion resin, and the effluent with a pH greater than 8 is collected until the effluent reaches 870 L.

[0129] The collected liquid after anion column separation was filtered through a microfiltration membrane to remove impurities and then concentrated using a counter-ion permeation membrane. The concentrated liquid had a specific gravity of 1.1 and was transferred to an alcohol precipitation tank. 15 kg of anhydrous ethanol was added with a stirring paddle at 400 rpm. Stirring was stopped after the ethanol addition, and the mixture was allowed to settle for 24 hours. The supernatant was collected and concentrated under reduced pressure to obtain a mulberry twig extract. The sample contained 63% alkaloids by weight, 23% polysaccharides by weight, 1% flavonoids by weight, and 5% amino acids by weight. Among the alkaloids, the content of 1-DNJ was 61.9%, FAG was 16.6%, and DAB was 11.1%.

[0130] Preparation Example 9 of Mulberry Extract

[0131] 1000 kg of fresh mulberry branches (Yue Sang No. 11) were crushed and added to 4000 L of water. The extracts were then heated and refluxed for 2 hours. The combined extracts were filtered to remove insoluble matter to obtain a crude extract. The crude extract was then heat-concentrated to a solids content of 4% and maintained at 50°C as the loading solution for a cationic resin column.

[0132] A 120 kg column of D113 macroporous weakly acidic phenyl propylene-based cationic resin was loaded and washed with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; then with 1 mol / L sodium hydroxide solution until the eluate pH reached 8.5; then with 2 mol / L hydrochloric acid until the eluate pH reached 4.5; and finally with 5 column volumes of deionized water to complete the activation. The concentrated extract was loaded and then eluted with 1000 L of 2.5 mol / L ammonia at a rate of 6 BV / h. The eluate from the cation column was collected when the pH was > 7. Collection was stopped when 900 L of the collected solution reached and the collected solution was directly passed through an anion column for purification.

[0133] Activate the column using a 45 kg column of D218 macroporous, strongly basic acrylic anion resin. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. Elute with 1.5 mol / L hydrochloric acid solution until the eluate has a pH of 3.5. Elute with 1.5 mol / L sodium hydroxide solution until the eluate has a pH of 9.0. The collected cation resin eluate is loaded onto the anion resin, and the effluent is collected until 870 L of effluent are reached.

[0134] After anion column separation, the collected liquid was filtered through a microfiltration membrane to remove impurities and then concentrated using a counter-ion permeation membrane. The concentrated liquid had a specific gravity of 1.1 and was transferred to an alcohol precipitation tank. 15 kg of anhydrous ethanol was added with a stirring paddle at 300 rpm. After the ethanol addition was complete, stirring was stopped. The alcohol precipitation was allowed to proceed for 24 hours. The supernatant was collected and concentrated under reduced pressure to obtain an extract. The sample contained 70% alkaloids by weight, 20% polysaccharides by weight, 0.6% flavonoids by weight, and 5% amino acids by weight. Among the alkaloids, the content of 1-DNJ was 70%, FAG was 13%, and DAB was 10%.

[0135] 2. Efficacy test of mulberry extract

[0136] Experimental Example 1: HFD diet-induced obese C57BL / 6 mouse model

[0137] Forty-five healthy male C57BL / 6 mice aged six weeks were randomly divided into a normal group (Chow), a high-fat model group (HFD), and a mulberry extract group (SZ-A), with nine mice in each group (see Table 1 below for specific experimental grouping and dosage). The mulberry extract was the mulberry branch extract prepared in Preparation Example 9. The mice in the normal group were fed with a basal diet, while the model group and the SZ-A group were fed with a high-fat diet (Research Diet, D12492, 60kcal% Fat); after feeding for eight weeks, each experimental group was given a corresponding dose of the test drug for six consecutive weeks. During the treatment period, the high-fat diet was continued, and the body weight and food and water intake of the animals were monitored. The model group was given normal saline. After the experiment, samples were collected for efficacy evaluation.

[0138] Table 1 Experimental groups and drug administration methods

[0139] Detection indicators:

[0140] 1) ELISA kit was used to detect serum prostate-specific antigen (PSA) levels.

[0141] 2) Prostate tissue was obtained for HE staining and the tissue morphology was observed under a microscope.

[0142] Experimental results:

[0143] Figure 1 shows that compared with the normal group, the serum PSA level in the model group mice was significantly increased, indicating prostate tissue lesions. SZ-A significantly reduced the serum PSA level in mice compared with the model group. PSA is a single-chain glycoprotein secreted by prostate epithelial cells and belongs to the kininase family of proteins. It is present in prostate tissue and semen, but its content in normal human serum is extremely low.

[0144] Figure 2 shows that in the blank group, the prostate glandular epithelial cells were single-layered and cuboidal, with finger-like protrusions visible in some areas, distinct glandular spaces, and clear tissue structure, with no abnormalities observed. Regular acini gradually tapered to low-cuboidal cells, arranged in a uniform single layer. In the model group, the glandular epithelial cells within the prostate ducts significantly proliferated, losing polarity and forming a stratified or pseudostratified structure that protruded into the glandular lumen. The epithelial cells were clustered and closely spaced within the glandular lumen, forming a sieve-like structure within the lumen, and the glandular lumen was significantly smaller. The glandular wall was significantly thickened, the density of the acini increased, the spaces between the ducts decreased significantly, and some adjacent glandular ducts were arranged back-to-back. Inflammatory cells were present in the glandular interstitium, and localized fibrous tissue proliferation was observed. Prostate tissue lesions in the SZ-A group all showed significant improvement, as evidenced by the single-layered cuboidal epithelial cells in some prostate ducts, enlarged glandular spaces, relatively clear tissue structure, and significantly reduced inflammatory cell infiltration in the glandular interstitium.

[0145] The above results show that SZ-A significantly reduces serum PSA levels and alleviates prostate tissue lesions, suggesting that SZ-A has a certain improvement effect on both prostatic hyperplasia and prostatitis.

[0146] Experimental Example 2: Effect of SZ-A on Human Prostate Hyperplasia Cell Model

[0147] Human prostate hyperplasia (BPH-1) cells were cultured in BPH-1-specific culture medium (RPMI-1640 + 20% FBS + 20 ng / mL testosterone + 0.5% ITS-G (100×) + 1% P / S). Cells were digested with 0.25% trypsin and harvested. Cells were seeded into 96-well plates at a density of 3 × 10 cells / well, with six replicates per group. After 24 hours of inoculation, adherent growth was observed until confluence reached approximately 50%. Cells were washed twice with PBS and then treated with 100 μL of complete culture medium containing different concentrations of SZ-A. SZ-A was replaced with saline as a control group. After 24 hours of exposure, 10 μL of CCK-8 solution was added in the dark. Two hours later, absorbance was measured using a microplate reader (at a wavelength of 450 nm, after continuous shaking for 15 seconds). Cell viability = (OD value of the treatment group - OD value of the blank control group) / (OD value of the control group - OD value of the blank control group × 100%). Cell viability was assessed using the CCK-8 assay. The results for BPH-1 cell viability in groups A1-A4 are shown in Figure 3 , and those in groups B1-B4 are shown in Figure 4 .

[0148] The groups and dosing were as follows:

[0149] Group A1: control group;

[0150] Group A2: drug administration group, 400 μg / mL SZ-A (calculated as extract, SZ-A is the Morus alba extract in Preparation Example 1);

[0151] Group A3: drug administration group, 400 μg / mL SZ-A (calculated as extract, SZ-A is the Morus alba extract in Preparation Example 2);

[0152] Group A4: drug administration group, 400 μg / mL SZ-A (calculated as extract, SZ-A is the Morus alba extract in Preparation Example 4);

[0153] Group B1: control group;

[0154] Group B2: drug administration group, 200 μg / mL SZ-A (calculated as alkaloids, SZ-A is the mulberry branch extract in Preparation Example 3);

[0155] Group B3: drug administration group, 200 μg / mL SZ-A (calculated as alkaloids, SZ-A is the mulberry branch extract in Preparation Example 7);

[0156] Group B4: drug administration group, 200 μg / mL SZ-A (calculated as alkaloids, SZ-A is the mulberry branch extract in Preparation Example 4);

[0157] The experimental results in Figures 3 and 4 show that SZ-A can inhibit the proliferation of BPH-1 cells.

Claims

1. Use of mulberry extract in preparing a medicament for treating and / or preventing prostate disease, characterized in that: Based on the weight percentage of the sum of the components of the mulberry extract as 100%, the mulberry extract contains 3% or more of alkaloids by weight (optionally containing 3-99% of alkaloids by weight, further optionally containing 15-99% of alkaloids by weight, further optionally containing 30-99% of alkaloids by weight, further optionally containing 40-99% of alkaloids by weight, further optionally containing 50-99% of alkaloids by weight, further optionally containing 60-99% of alkaloids by weight), and / or contains no more than 70% polysaccharide by weight (optionally containing 0.2-70% polysaccharide by weight, further optionally containing 0.2-50% polysaccharide by weight, further optionally containing 0.2-35% polysaccharide by weight, further optionally containing 0.2-25% polysaccharide by weight, further optionally containing 0.2-23% polysaccharide by weight, further optionally containing 20-25% polysaccharide by weight), and / or contains flavonoids in an amount not higher than 10% by weight (optionally containing flavonoids in an amount of 0.05-5% by weight, further optionally containing flavonoids in an amount of 0-2% by weight, further optionally containing flavonoids in an amount of 0.05-2% by weight, further optionally containing flavonoids in an amount of 0.5-1.5% by weight, further optionally containing flavonoids in an amount of 0-1% by weight, further optionally containing flavonoids in an amount of 0.05-1% by weight), and / or contains no more than 50% by weight of amino acids (optionally containing 0-30% by weight of amino acids, further optionally containing 0-25% by weight of amino acids, further optionally containing 0-20% by weight of amino acids, further optionally containing 0-5% by weight of amino acids, further optionally containing 3-25% by weight of amino acids or further optionally containing 5-20% by weight of amino acids), and / or other components (the weight content can be optionally 0-25%, further optionally 0-20%, further optionally 0-15%, further optionally 0-11%, further optionally 2-20%, further optionally 4-8%).

2. The use according to claim 1, characterized in that The prostate disease includes at least one of prostatitis and benign prostatic hyperplasia; Optionally, the prostatitis includes at least one of acute bacterial prostatitis, chronic bacterial prostatitis, chronic non-bacterial prostatitis, chronic pelvic pain syndrome, and asymptomatic prostatitis.

3. The use according to claim 1 or 2, characterized in that Treatment and / or prevention of benign prostatic hyperplasia manifested by at least one of the following: 1) Reduce prostate-specific antigen (PSA) levels; 2) Alleviate pathological damage to prostate tissue; 3) Inhibit the proliferation of prostate hyperplasia cells.

4. The use according to any one of claims 1 to 3, characterized in that Treatment and / or prevention of prostatitis manifested by at least one of the following: (1) Alleviate the pathological damage of the patient's prostate tissue; (2) Reduce prostate-specific antigen (PSA) levels.

5. The use of mulberry extract is at least one of the following (a1) to (a3): (a1) Use in the preparation of a medicament for reducing prostate-specific antigen (PSA) content; (a2) Use in the preparation of a medicament for alleviating pathological damage to prostate tissue; (a3) Use in the preparation of a medicament for inhibiting the proliferation of prostate hyperplasia cells; It is characterized by: Based on the weight percentage of the sum of the components of the mulberry extract as 100%, the mulberry extract contains 3% or more of alkaloids by weight (optionally containing 3-99% of alkaloids by weight, further optionally containing 15-99% of alkaloids by weight, further optionally containing 30-99% of alkaloids by weight, further optionally containing 40-99% of alkaloids by weight, further optionally containing 50-99% of alkaloids by weight, further optionally containing 60-99% of alkaloids by weight), and / or contains no more than 70% polysaccharide by weight (optionally containing 0.2-70% polysaccharide by weight, further optionally containing 0.2-50% polysaccharide by weight, further optionally containing 0.2-35% polysaccharide by weight, further optionally containing 0.2-25% polysaccharide by weight, further optionally containing 0.2-23% polysaccharide by weight, further optionally containing 20-25% polysaccharide by weight), and / or contains flavonoids in an amount not higher than 10% by weight (optionally containing flavonoids in an amount of 0.05-5% by weight, further optionally containing flavonoids in an amount of 0-2% by weight, further optionally containing flavonoids in an amount of 0.05-2% by weight, further optionally containing flavonoids in an amount of 0.5-1.5% by weight, further optionally containing flavonoids in an amount of 0-1% by weight, further optionally containing flavonoids in an amount of 0.05-1% by weight), and / or contains no more than 50% by weight of amino acids (optionally containing 0-30% by weight of amino acids, further optionally containing 0-25% by weight of amino acids, further optionally containing 0-20% by weight of amino acids, further optionally containing 0-5% by weight of amino acids, further optionally containing 3-25% by weight of amino acids or further optionally containing 5-20% by weight of amino acids), and / or other components (the weight content can be optionally 0-25%, further optionally 0-20%, further optionally 0-15%, further optionally 0-11%, further optionally 2-20%, further optionally 4-8%).

6. The use according to any one of claims 1 to 5, characterized in that Taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are as follows: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, based on the mulberry extract, the weight content of each component is: Optionally, based on the mulberry extract, the weight content of each component is: Optionally, based on the mulberry extract, the weight content of each component is: Optionally, based on the mulberry extract, the weight content of each component is: Optionally, based on the mulberry extract, the weight content of each component is: The weight content of each component in the mulberry extract is: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight percentages of the components in the mulberry extract are: Further optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight contents of the components in the mulberry extract are: Further optionally, taking the sum of the weight percentages of the components of the mulberry extract as 100%, the weight contents of the components in the mulberry extract are: More preferably, the alkaloids include 1-deoxynojirimycin (DNJ), N-methyl-1-deoxynojirimycin (N-methly-1-deoxynojirimycin), fagomine (FAG), 3-epi-fagomine, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), calystegin B2, calystegin C1, 2-oxy-(α- One or more of 2-O-(α-D-galactopyranosyl)-1-deoxynojirimycin, 6-O-(β-D-glucopyranosyl)-1-deoxynojirimycin, and 1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol; Optionally, the weight percentage of DNJ is not less than 50% (optionally 60-99%) of the total alkaloids.

7. The use according to any one of claims 1 to 6, characterized in that The preparation method of the mulberry extract comprises the following steps: 1) preparing a crude extract of a Moraceae plant; 2) separating the crude extract through a cationic resin and / or an optional anionic resin to obtain the mulberry extract; Preferably, the method further comprises the following steps: 3) performing alcohol precipitation on the resin effluent from step 2) and collecting the supernatant; 4) concentrating and / or drying the supernatant; Optionally, the method further comprises the following step: concentrating and / or drying the resin effluent from step 2).

8. The use according to any one of claims 1 to 7, characterized in that The mulberry extract acts on humans or mammals.

9. The use according to any one of claims 1 to 8, characterized in that The medicine is in the form of oral administration.

10. The use according to any one of claims 1 to 9, characterized in that The medicine is in the form of tablets, capsules, oral solutions, oral emulsions, pills, granules, syrups or powders.

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