Bilobalide composition and application thereof in preparation of medicine for preventing and / or treating hemolytic jaundice

Abstract

The invention provides a bilobalide composition and application of the bilobalide composition in preparation of a medicine for preventing and / or treating hemolytic jaundice. The bilobalide composition disclosed by the invention is mainly prepared from bilobalide A, bilobalide B, bilobalide C, bilobalide J and bilobalide. Experiments show that the bilobalide composition provided by the invention obviously reduces the serum TBIL, DBIL, IBIL and TBA levels of hemolytic jaundice model mice, improves the symptoms of hemolytic jaundice, and provides a new medication choice for preventing and treating hemolytic jaundice.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, and particularly relates to a ginkgolide composition and its application in the preparation of drugs for preventing and / or treating hemolytic jaundice. Background Art

[0002] Hemolytic jaundice is caused by various factors leading to hemolysis, excessive destruction of red blood cells, formation of a large amount of unconjugated bilirubin, which exceeds the uptake, conjugation, and excretion capacity of hepatocytes; on the other hand, due to anemia, hypoxia, and the toxic effects of red blood cell breakdown products caused by hemolysis, the metabolic function of hepatocytes for bilirubin is weakened, resulting in the retention of unconjugated bilirubin in the blood, exceeding the normal level and presenting jaundice.

[0003] Ginkgo biloba contains chemical components such as flavonoids, terpene lactones, phenolic acids, polyprenols, etc. Ginkgo biloba extract (GBE) is an extract isolated and purified from Ginkgo biloba leaves, mainly containing flavonoid and terpene lactone compounds, which are the main active components of Ginkgo biloba leaves and have strong pharmacological activities. Ginkgo biloba extract is prepared from Ginkgo biloba leaves by ethanol reflux extraction. The extraction solutions are combined and concentrated to an appropriate amount, and then eluted successively with water and ethanol of different concentrations on a macroporous adsorption resin column. The eluates are collected, ethanol is recovered, and the dried extract with enriched active ingredients is obtained, which is a light yellow-brown, flowable powder with a bitter taste. The Chinese Pharmacopoeia (2020 Edition) stipulates that, calculated on the dried product, the content of total ginkgo flavonoids (including quercetin, kaempferol, isorhamnetin) is ≥ 24.0%, the content of terpene lactones (including bilobalide, ginkgolide A, ginkgolide B, ginkgolide C) is ≥ 6.0%, and the total ginkgolic acid content shall not exceed five parts per million.

[0004] Ginkgolide is a terpene compound, also known as ginkgo terpene lactone, which is composed of sesquiterpene lactones and diterpene lactones and is an active ingredient of Ginkgo biloba leaves. The diterpene lactones among them include ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M, ginkgolide K, and ginkgolide L, while the sesquiterpene lactone is bilobalide. As a main active ingredient in GBE, ginkgolide has obvious effects on diseases such as stroke and Alzheimer's disease. Ginkgolide is a strong platelet-activating factor antagonist, which has a protective effect on ischemic injuries of the central nervous system and immune system, and also has anti-allergic and anti-shock effects.

[0005] There are many methods for the extraction and purification of ginkgolides, but none of them can effectively isolate ginkgolides with high content. Moreover, the components of the terpene lactones obtained by different separation processes are different, which leads to different drug effects of the ginkgolides prepared by different extraction and purification methods. The present invention provides a ginkgolide composition with a fixed component ratio and a clear and definite product structure, and creatively uses it in the preparation of drugs for preventing and treating hemolytic jaundice. So far, there has been no relevant report. Summary of the Invention

[0006] The object of the present invention is achieved by the following solutions.

[0007] The present invention provides a ginkgolide composition, which is mainly composed of ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), ginkgolide J (GJ) and bilobalide (BB).

[0008] Furthermore, the contents of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J and bilobalide in the ginkgolide composition are not less than 40%.

[0009] Furthermore, by weight ratio, in the ginkgolide composition, ginkgolide J:ginkgolide C:bilobalide:ginkgolide A:ginkgolide B = 1:(2.5 - 3.5):(15 - 25):(4 - 6):(3 - 5).

[0010] Even further, by weight ratio, in the ginkgolide composition, ginkgolide J:ginkgolide C:bilobalide:ginkgolide A:ginkgolide B = 1:3:19:5:4.

[0011] The structural formulas of each component of ginkgolide are as follows:

[0012]

[0013] When R1 = OH, R2 = H, R3 = H, the above formula is the structural formula of ginkgolide A;

[0014] When R1 = OH, R2 = OH, R3 = H, the above formula is the structural formula of ginkgolide B;

[0015] When R1 = OH, R2 = OH, R3 = OH, the above formula is the structural formula of ginkgolide C;

[0016] When R1 = H, R2 = H, R3 = OH, the above formula is the structural formula of ginkgolide J.

[0017] The structural formula of bilobalide is as follows:

[0018]

[0019] The preparation method of the ginkgolide composition of the present invention comprises the following steps:

[0020] Step (a): Take the crude ginkgolide, add ethyl acetate, and the mass-volume ratio (g:mL) of the crude ginkgolide to ethyl acetate is 1:10 - 1:30. Stir and extract at room temperature once for 1 h to obtain an extract. After concentration and drying, a first refined ginkgolide product is obtained.

[0021] In one embodiment of the present invention, the mass-volume ratio (g:mL) of the crude ginkgolide to ethyl acetate in step (a) is 1:20.

[0022] Furthermore, the preparation method of the ginkgolide composition of the present invention further comprises the following steps:

[0023] Step (b): Take the above refined product, add absolute ethanol, and the mass-volume ratio (g:mL) of the first refined ginkgolide product to absolute ethanol is 1:2 - 1:6. Heat under reflux for dissolution and then filter. Dropwise add distilled water, control the dropping rate to 1 drop per second. The volume of water added is equal to the volume of the dissolution solution. After the addition is completed, stir and crystallize for 2 - 4 h, filter, and dry to obtain a second refined ginkgolide product.

[0024] In one embodiment of the present invention, the mass-volume ratio (g:mL) of the first refined ginkgolide product to absolute ethanol in step (b) is 1:4, and in step (b), the stirring and crystallization is carried out for 3 h.

[0025] The present invention also provides a method for detecting the ginkgolide composition by high performance liquid chromatography. The specific detection method is as follows:

[0026] A reversed-phase high performance liquid chromatography system equipped with an autosampler (Ultimate3000, Thermo Fisher Scientific, USA), an ultraviolet absorption detector (UV) for perfluorooctanesulfonic acid, and an evaporative light scattering detector (CAD). Use a reversed-phase column (250×4.6 mm, 5 μm; Welch Ultimate LP-C18). The injection volume is 5 μL. The flow rate is 1.0 mL / min. The column temperature is 30°C. The detection wavelength is 360 nm, and the mobile phase is 0.4% (v / v) phosphoric acid water and methanol (50:50).

[0027] The data acquisition frequency of the CAD detector is 10 Hz, the filter is 5.0, and the evaporation tube temperature is set low. The mobile phase is tetrahydrofuran - methanol - water (10∶25∶65).

[0028] Another object of the present invention is to provide an application of a ginkgolide composition in a drug for preventing and / or treating hemolytic jaundice.

[0029] Furthermore, the hemolytic jaundice is congenital hemolytic jaundice or acquired hemolytic jaundice.

[0030] Still further, the congenital hemolytic jaundice is jaundice caused by thalassemia or hereditary spherocytosis.

[0031] Still further, the acquired hemolytic jaundice is jaundice caused by immune hemolysis, mechanical hemolysis, hemolysis caused by drugs and chemical poisons, hemolysis caused by physical factors, hemolysis caused by biological factors, or hemolysis caused by diseases.

[0032] Still further, the immune hemolysis is selected from autoimmune hemolysis, post-transfusion hemolysis due to blood group incompatibility, and hemolysis of the newborn; the mechanical hemolysis is red blood cell damage caused by an artificial heart valve; the hemolysis caused by drugs and chemical poisons is selected from hemolysis caused by sulfonamides or benzene; the hemolysis caused by physical factors is hemolysis caused by extensive burns or radiation; the hemolysis caused by biological factors is hemolysis caused by malaria, hemolytic streptococcus infection, or snake venom; the hemolysis caused by diseases is hemolysis caused by hypersplenism or paroxysmal nocturnal hemoglobinuria.

[0033] Furthermore, the drug for preventing and / or treating hemolytic jaundice further comprises a pharmaceutically acceptable excipient.

[0034] Specifically, the drug for preventing and / or treating hemolytic jaundice is prepared as an oral dosage form or an injection dosage form.

[0035] Furthermore, the drug for preventing and / or treating hemolytic jaundice is prepared as a capsule, tablet, powder for injection, granule, pill, injection, decoction extract, suspension, dispersant, syrup, suppository, gel, or oral liquid.

[0036] As used herein, the term "treatment" and other similar synonyms include alleviating, reducing, or improving the symptoms of a disease or disorder, inhibiting a disease or disorder, such as preventing the development of a disease or disorder, alleviating a disease or disorder, improving a disease or disorder, alleviating the symptoms caused by a disease or disorder, or terminating the symptoms of a disease or disorder, preventing other symptoms, improving or preventing the underlying metabolic causes of the symptoms, and further, the term encompasses the purpose of prevention. The term also includes obtaining a therapeutic effect and / or a preventive effect. The therapeutic effect refers to curing or improving the underlying disease being treated. In addition, the cure or improvement of one or more physiological symptoms associated with the underlying disease is also a therapeutic effect, for example, although the patient may still be affected by the underlying disease, an improvement in the patient's condition is observed. In terms of the preventive effect, the composition may be administered to a patient at risk of developing a specific disease, or even if a disease diagnosis has not been made, the composition may be administered to a patient presenting one or more physiological symptoms of the disease.

[0037] As used herein, the term "pharmaceutically acceptable" refers to a substance (such as a carrier or diluent) that does not affect the biological activity or properties of the ginkgolide composition of the present invention and is relatively non-toxic, that is, the substance can be administered to an individual without causing adverse biological reactions or interacting with any components contained in the composition in an adverse manner.

[0038] As used herein, the terms "patient" and "individual" refer to mammals. Mammals can be humans, non-human primates, mice, rats, dogs, cats, horses or cows, but are not limited to these examples.

[0039] Compared with the prior art, the present invention has achieved the following beneficial technical effects:

[0040] After the ginkgolide composition of the present invention intervenes in the hemolytic jaundice animal model, the ginkgolide composition can significantly improve the related symptoms of hemolytic jaundice. By examining the changes in blood indexes, the results show that the ginkgolide composition of the present invention can reduce the levels of serum TBIL, DBIL, IBIL, and TBA in the hemolytic jaundice model mice. In addition, after administration of the ginkgolide composition of the present invention, the state of the hemolytic jaundice model mice is significantly improved, indicating that the ginkgolide composition of the present invention has a definite preventive and therapeutic effect on hemolytic jaundice. Description of the Drawings

[0041] Figure 1 Chromatogram of the reference substance.

[0042] Figure 2 Liquid chromatogram of crude ginkgolide.

[0043] Figure 3 Liquid chromatogram of the first refined ginkgolide.

[0044] Figure 4 Liquid chromatogram of the second refined ginkgolide.

[0045] Figure 5 Levels of serum TBIL, DBIL, IBIL, and TBA in each group of mice.

[0046] Note: Compared with the normal control group, *P < 0.05, **P < 0.01, ***P < 0.001; compared with the model control group, #P < 0.05, ##P < 0.01, P < 0.001. Detailed Description of the Invention

[0047] The present invention will be further described below through specific embodiments so as to better understand the solution and advantages of the present invention. However, the specific content described below is only for illustration and not a limitation of the invention. Substitutions and / or combinations of the technical features of the present invention are obvious to those skilled in the art within the content, spirit and / or scope of the present invention and are included in the present invention.

[0048] Preparation Example 1

[0049] Weigh 8 kg of ginkgo leaves, perform alcohol extraction with a 20% ethanol solution at a material-liquid ratio of 1:15, reflux and extract twice, combine the extraction solutions and concentrate to a density of 1.1 - 1.2. Load the concentrated solution onto macroporous resin (D101), with a column volume of 1 L / kg of crude drug. First, elute with water for 6 times the volume, then elute with 60% ethanol for 8 times the volume and collect the ethanol eluate. Concentrate the eluate until alcohol-free, perform extraction with ethyl acetate at a ratio of 1:1, and extract three times in the same way. Combine the ester phases to obtain the aqueous phase and the ethyl acetate phase respectively. Concentrate and dry the ethyl acetate phase, dissolve it with 50% ethanol, with a volume of 0.05 L / kg of crude drug, and add activated carbon with an addition amount of 0.1% of the crude drug, and stir at 80 °C for 1 h for deacidification. Perform secondary deacidification under the same conditions, and dry the concentrated filtrate to obtain the crude ginkgolide.

[0050] The content of terpenoid lactones in the crude ginkgolide was detected by high performance liquid chromatography. The specific determination method is as follows:

[0051] A reversed-phase high performance liquid chromatography system equipped with an autosampler (Ultimate 3000, Thermo Fisher Scientific, USA), an ultraviolet absorption detector (UV) for perfluorooctanesulfonic acid, and a charged aerosol detector (CAD). Use a reversed-phase column (250×4.6 mm, 5 μm; Welch Ultimate LP-C18). The injection volume is 5 μL. The flow rate is 1.0 mL / min. The column temperature is 30 °C. The detection wavelength is 360 nm, and the mobile phase is 0.4% (v / v) phosphoric acid water and methanol (50:50).

[0052] The data acquisition frequency of the CAD detector is 10 Hz, the filter is 5.0, and the evaporation tube temperature is set low. The mobile phase is tetrahydrofuran - methanol - water (10∶25∶65).

[0053] The content of terpenoid lactones in the crude ginkgolide measured by the above method was 45.47%. The chromatogram of the reference substance is as Figure 1 shown, and the liquid chromatogram of the crude ginkgolide is as Figure 2 shown. The contents of each component are shown in Table 1.

[0054] Table 1 Content of terpenoid lactones in the crude ginkgolide

[0055] GJ / % GC / % BB / % GA / % GB / % Total / % TTLs 1.58 5.38 26.31 6.87 5.33 45.47

[0056] Preparation Example 2

[0057] Take the crude ginkgolide obtained in Preparation Example 1 above, add ethyl acetate, and the mass-to-volume ratio (g:mL) of the crude ginkgolide to ethyl acetate is 1:20. Stir and extract at room temperature once for 1 h to obtain an extract. Concentrate and dry it to obtain the first refined product of ginkgolide.

[0058] Using the detection method in Preparation Example 1, the content of terpenoid lactones in the first refined product of ginkgolide was measured to be 67.90%. The liquid chromatogram of the first refined product of ginkgolide is as Figure 3 shown, and the content of each component is shown in Table 2.

[0059] Table 2 Content of Terpenoid Lactones in the First Refined Product of Ginkgolide

[0060] GJ / % GC / % BB / % GA / % GB / % Total / % TTLs 2.13 6.86 42.09 9.47 7.35 67.90

[0061] Preparation Example 3

[0062] Take the crude ginkgolide obtained in Preparation Example 1 above, add ethyl acetate, and the mass-to-volume ratio (g:mL) of the crude ginkgolide to ethyl acetate is 1:20. Stir and extract at room temperature once for 1 h to obtain an extract. Concentrate and dry it to obtain the first refined product of ginkgolide.

[0063] Take the above first refined product of ginkgolide, add absolute ethanol, and the mass-to-volume ratio (g:mL) of the first refined product of ginkgolide to absolute ethanol is 1:4. Heat under reflux to dissolve and then filter. Dropwise add distilled water, control the dropping rate at 1 drop / 1 s. The volume of water added is equal to the volume of the dissolution solution. After dropping, stir and crystallize for 3 h, filter, and dry to obtain the second refined product of ginkgolide.

[0064] Using the detection method in Preparation Example 1, the content of terpenoid lactones in the second refined product of ginkgolide was measured to be 91.87%. The liquid chromatogram of the second refined product of ginkgolide is as Figure 4 shown, and the content of each component is shown in Table 3.

[0065] Table 3 Content of Terpenoid Lactones in the Second Refined Product of Ginkgolide

[0066] GJ / % GC / % BB / % GA / % GB / % Total / % TTLs 2.80 8.18 58.18 12.61 10.10 91.87

[0067] Pharmacodynamic Example Study on the Effect of Ginkgolide Composition on Hemolytic Jaundice Mice

[0068] 1. Experimental Materials

[0069] 1.1 Drugs

[0070] Ginkgolide composition, provided by Shandong Xinsdai Pharmaceutical Co., Ltd., prepared according to the method of Preparation Example 1 above;

[0071] Acetylphenylhydrazine, sourced from Aladdin, batch number L2106080.

[0072] 1.2 Experimental animals

[0073] 50 male ICR mice, 6 - 7 weeks old, weighing 30g - 34g. Experimental animal license number: SYXK(Shandong)20180008, adaptively raised in the experimental center of Lunan Pharmaceutical Group, maintaining the indoor relative temperature at 19 - 21°C, relative humidity at 50% - 70%, day / night time at 12h / 12h, fed with standard feed and drinking water.

[0074] 2. Experimental methods

[0075] 2.1 Model establishment and administration

[0076] The 50 mice were randomly divided into a normal control group, a model control group, a YXNZ - L group, a YXNZ - M group, and a YXNZ - H group according to body weight, with 10 mice in each group. Except for the normal control group, mice in other groups were intraperitoneally injected with 60mg / kg acetylphenylhydrazine (APH) on the first day, and 30mg / kg acetylphenylhydrazine (APH) was intraperitoneally injected every day after 48h to maintain the model. The normal control group was injected with an equal volume of normal saline, and the model establishment period was 19 days. At the same time as the start of model establishment, each administration group of the ginkgolide composition was given the ginkgolide composition by gavage every day for 21 consecutive days. The model control group and the normal control group were given an equal volume of solvent. Compared with the normal control group, the mice in the model control group were irritable, their fur lost luster, the skin of their ears and other parts turned yellow, and their urine and feces were yellow, indicating successful model establishment.

[0077] The animal grouping and administration doses are shown in the following table.

[0078]

[0079] Note: C represents the normal control group; V represents the model control group.

[0080] The YXNZ - L group was given the ginkgolide composition obtained in Preparation Example 1 by gavage at a dose of 5.4mg / kg; the YXNZ - M group was given the ginkgolide composition obtained in Preparation Example 1 by gavage at a dose of 16.2mg / kg; the YXNZ - H group was given the ginkgolide composition obtained in Preparation Example 1 by gavage at a dose of 48.6mg / kg.

[0081] 2.2 Test observation

[0082] 2.2.1 General condition observation

[0083] Before modeling, after modeling, and after treatment with the ginkgolide composition, the general conditions of the mice such as body weight were observed.

[0084] 2.2.2 Blood biochemical indices

[0085] 48 hours after the end of modeling, anesthesia was performed 2 hours after the last administration to collect blood, and the serum was detected for the indices of total bilirubin (TBIL), indirect bilirubin (IBIL), direct bilirubin (DBIL), and total bile acid (TBA).

[0086] 3. Data analysis

[0087] The SPSS 26.0 software system was used for statistical analysis of the data. Measurement data were expressed as mean ± standard deviation. The independent samples t-test or one-way ANOVA was used for comparison between groups, and the homogeneity of variance test was used for comparability between groups. A significant difference was considered when P < 0.05.

[0088] 4. Experimental results

[0089] 4.1 General conditions of the mice

[0090] Before modeling, the mice in each group were active and flexible, foraged actively, struggled strongly when grabbed, had moist fur, rosy claws and ears, and normal urination and defecation. There was no significant difference in body weight between the groups of mice (P > 0.05). Compared with the normal control group of mice, 48 hours after injection of acetylphenylhydrazine, the mice in the low, medium, and high-dose groups of the ginkgolide composition and the model control group showed slow reaction, basically no eating and activity, and individual mice showed prostration, twitching, irritability, and clustering. The fur of the mice lost luster, the ear skin was sallow, the urine was yellow, the feces were yellow, and they struggled weakly when grabbed. After modeling, the body weight gain of the mice was affected. Compared with the normal control group of mice, the body weight of the mice in the model control group was lighter (P < 0.05), indicating poor body weight gain after modeling.

[0091] Before treatment, there were no significant differences in the body weights of mice in the low, medium, and high-dose groups of the ginkgolide composition and the model control group. After intragastric administration of the ginkgolide composition for 1 week, the mice in the low-dose group were still sluggish, with basically no obvious eating or activity, pale yellow ears, soy sauce-colored urine, red and slightly loose stools, still lying prone, twitching, irritable, and huddled together, and there was no obvious escape or struggle when grabbed. In the medium- and high-dose groups of mice, the sluggishness improved slightly compared with before, and they began to eat and move occasionally, with pale yellow ears, soy sauce-colored urine, red and loose stools, and there were still cases of lying prone, twitching, irritability, and huddling together, and slight escape and struggle phenomena began to appear when grabbed. After continuing to administer the drug for 21 days, the mice in the low-dose group of the ginkgolide composition showed a slight improvement in sluggishness compared with before, ate and moved occasionally, had light yellow ears, soy sauce-colored urine, red and slightly loose stools, and there were still cases of lying prone, twitching, irritability, and huddling together, and slight escape and struggle phenomena began to appear when grabbed. In the medium- and high-dose groups of the ginkgolide composition, the reaction of the mice improved compared with before, they could respond to stimuli, the amount of eating and activity increased, the fur began to show slight moistening, the ear skin began to turn red and was light pink, the urine was lighter yellow than before, the stools were slightly formed, the color began to darken, and the cases of lying prone, twitching, irritability, and huddling together improved significantly. Compared with the model control group, there were no significant differences in the body weights of mice in the low, medium, and high-dose groups of the ginkgolide composition after treatment (P>0.05).

[0092] 4.2 Results of blood biochemical indexes

[0093] The results were as Figure 5 shown. Compared with the normal control group, the contents of serum TBIL, DBIL, IBIL, and TBA in the model control group of mice were all significantly increased (P<0.001). Compared with the model control group, the contents of serum TBIL, DBIL, and IBIL in the medium-dose group of the ginkgolide composition were all significantly decreased (P<0.01), and the contents of serum TBIL, DBIL, and IBIL in the high-dose group of the ginkgolide composition were all significantly decreased (P<0.001), and the content of serum TBA in the mice was significantly decreased (P<0.05). Compared with the normal control group, there were no significant differences in the contents of TBIL, DBIL, IBIL, and TBA in the high-dose group of the ginkgolide composition (P>0.05).

[0094] The applicant conducted a hemolytic jaundice experiment on the ginkgolide compositions obtained in Preparation Examples 2 and 3 according to the above-mentioned pharmacodynamic experiment method. The results showed that the ginkgolide compositions obtained in Preparation Examples 2 and 3 (ginkgolide compositions with the contents of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide above 40%) had a significant therapeutic effect on hemolytic jaundice and significantly improved indexes such as TBIL, DBIL, IBIL, and TBA.

[0095] The above embodiments are not any formal limitations on the present invention. For those skilled in the art, any modifications, substitutions, etc. made within the scope of the technical solution of the present invention based on the technical essence of the present invention still fall within the protection scope of the technical solution of the present invention.

Claims

1. A ginkgolide composition, characterized in that: The ginkgolide composition mainly consists of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J and bilobalide.

2. The ginkgolide composition according to claim 1, characterized in that: The contents of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J and bilobalide in the ginkgolide composition are not less than 40%.

3. The ginkgolide composition according to claim 1, characterized in that: In terms of weight ratio, the ginkgolide composition comprises ginkgolide J: ginkgolide C: bilobalide: ginkgolide A: ginkgolide B=1:(2.5-3.5):(15-25): (4-6)：(3-5)。 4. The ginkgolide composition according to claim 3, characterized in that: In terms of weight ratio, in the ginkgolide composition, ginkgolide J: ginkgolide C: bilobalide: ginkgolide A: ginkgolide B=1:3:19:5:

4.

5. Use of the ginkgolide composition according to any one of claims 1 to 4 in the preparation of a medicament for preventing and / or treating hemolytic jaundice.

6. The use according to claim 5, characterized in that The hemolytic jaundice is congenital hemolytic jaundice or acquired hemolytic jaundice.

7. The use according to claim 6, characterized in that The congenital hemolytic jaundice is jaundice caused by thalassemia or hereditary spherocytosis.

8. The use according to claim 6, characterized in that The acquired hemolytic jaundice is one or more of jaundice caused by immune hemolysis, mechanical hemolysis, hemolysis caused by drugs and chemical poisons, hemolysis caused by physical factors, hemolysis caused by biological factors or hemolysis caused by disease.

9. The use according to any one of claims 6 to 8, characterized in that: The drug for preventing and / or treating hemolytic jaundice also includes pharmaceutically acceptable excipients.

10. The use according to claim 9, characterized in that The drug for preventing and / or treating hemolytic jaundice is prepared as an oral preparation or an injectable preparation.

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