Application of a small molecule inhibitor, Geraniin, in the preparation of drugs for treating echinococcosis.

Abstract

This invention belongs to the field of biomedical technology, specifically relating to the application of the small molecule inhibitor Geraniin in the preparation of drugs for treating echinococcosis. Addressing the clinical challenges of limited efficacy and easy development of drug resistance in existing treatments for echinococcosis, this invention targets the EmAGO2 protein, which is specifically highly expressed in the germinal layer cells of echinococcosis, and screens for a high-affinity small molecule inhibitor, Geraniin. The binding affinity constant (KD) of Geraniin to EmAGO2 is 90.8 nM, and the equilibrium dissociation constant (KD) is 14.00 nM. In vitro experiments show its IC50 against protocercariae. 50 At a concentration of 10.27 μM, it can significantly inhibit vesicle growth; in vivo experiments showed that oral treatment with 40 mg / kg and 80 mg / kg Geraniin had the same efficacy as the first-line clinical drug albendazole, and good safety.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of a small molecule inhibitor, Geraniin, in the preparation of drugs for treating echinococcosis. Background Technology

[0002] Alveolar echinococcosis (AE), also known as alveolar echinococcosis, is a serious zoonotic parasitic disease caused by infection with the larvae of the tapeworm *Echinococcus multilocularis*. This disease is characterized by its prolonged course and far-reaching impact; its lesions exhibit invasive growth characteristics similar to malignant tumors and have the ability to metastasize to distant sites, hence it is clinically referred to as "parasitic cancer." The overall clinical prognosis for patients is extremely poor. Clinical statistics show that the mortality rate of AE patients who do not receive standardized or adequate treatment is as high as 90% within 10-15 years. This not only places a heavy physical, psychological, and economic burden on patients and their families but also puts enormous pressure on the public health system.

[0003] Currently, the standard clinical treatment for echinococcosis (AE) primarily involves surgical resection, supplemented by adjuvant drug therapy. However, this treatment system faces numerous insurmountable bottlenecks in practical application. On the one hand, most AE patients exhibit multifocal lesions, often showing diffuse infiltrative growth within the liver tissue, resulting in only about 30% of patients being candidates for surgical resection. On the other hand, even when patients undergo surgery, the recurrence rate remains high, making it difficult to achieve the expected overall treatment outcome. Regarding drug therapy, the only clinically approved drug for AE is albendazole. This class of drugs has inherent drawbacks, including limited efficacy and the potential for long-term use to induce drug resistance in the parasite, further exacerbating the clinical treatment challenges of AE. Therefore, developing novel, highly effective, and low-toxicity drugs for AE has become a critical medical challenge that urgently needs to be overcome in this field.

[0004] Echinococcus multilocularis larvae can achieve tumor-like unlimited proliferation in the human body. The core pathological mechanism lies in the continuous proliferation and differentiation of the parasite's germinal layer cells, which constantly form new vesicles and produce a large number of protoscolex, thereby promoting the invasive growth of lesions. In recent years, research on the maintenance mechanism of parasite stem cells has provided new research directions for the discovery of anti-AE drug targets. However, most reported anti-AE candidate targets, such as tubulin, EGFR signaling pathway-related molecules, and various metabolic enzymes, have high sequence homology with their host counterparts, posing a potential risk of off-target toxicity to drugs developed based on these targets. Furthermore, most existing anti-AE drugs primarily target the adult parasite or protoscolex, with very limited inhibitory effects on the germinal layer stem cells driving the unlimited proliferation of lesions. Therefore, developing a novel drug target that can efficiently inhibit Echinococcus multilocularis larvae proliferation while possessing high host specificity and low systemic toxicity remains a core technical problem that urgently needs to be solved in the treatment of Echinococcus multilocularis disease.

[0005] Based on genome-wide alignment and single-cell transcriptome sequencing analysis, it was discovered that *Echinococcus multilocularis* has lost the Piwi gene family, which is essential for maintaining traditional stem cell pluripotency, during its evolution. However, it has simultaneously evolved a new group of tapeworm-specific Argonaute proteins, named EmAGOs, which includes three members: EmAGO2, EmAGO3, and EmAGO4. EmAGO2 exhibits highly specific expression in the germinal layer cells of *Echinococcus multilocularis* larvae. This expression pattern suggests that EmAGO2 may play a crucial regulatory role in the lineage maintenance and proliferation of *Echinococcus multilocularis* stem cells, possessing the potential to become a target for anti-AE drugs. Further amino acid sequence alignment analysis showed that EmAGO2 has low homology with human and mouse AGO2 proteins, and their key functional domains differ significantly. Therefore, drugs targeting EmAGO2 are less likely to interfere with the normal physiological function of the host's own AGO2 protein, theoretically possessing lower systemic toxicity and a wider therapeutic window.

[0006] To date, there are no reports in existing technologies regarding the screening of small molecule inhibitors using the EmAGO2 protein, a specific protein of Echinococcus multilocularis, as a direct drug target, and the use of the screened inhibitors for the treatment of Echinococcus multilocularis larvae. Summary of the Invention

[0007] The purpose of this invention is to provide the application of the small molecule inhibitor Geraniin in the preparation of drugs for treating echinococcosis, clarifying the molecular mechanism by which Geraniin exerts its anti-echinococcosis effect, and providing a solid theoretical basis for its subsequent drug development and clinical translation.

[0008] The objective of this invention is achieved through the following technical solution: This invention provides the use of Geraniin in the preparation of drugs for treating echinococcosis, the structural formula of which is shown below: .

[0009] Furthermore, the Geraniin targets and binds to the EmAGO2 protein of Echinococcus multilocularis, and the two bind with a significantly high affinity.

[0010] Furthermore, the binding affinity constant KD of Geraniin to EmAGO2 protein is 90.8 nM, and the equilibrium dissociation constant KD is 14.00 nM.

[0011] Furthermore, the aforementioned echinococcosis is caused by infection with Echinococcus multilocularis, and its characteristic pathological change is that the protoscolex continuously produces new vesicles in the host through exophytic budding reproduction, forming vesicle clusters or masses.

[0012] Furthermore, the drug is in the form of an oral dosage form.

[0013] Furthermore, when administering Geraniin, it is first dissolved in DMSO, then diluted with physiological saline before administration, and the dosage of Geraniin in the drug is not less than 40 mg / kg.

[0014] Furthermore, when Geraniin is administered orally at a dose of 40 mg / kg or 80 mg / kg, its therapeutic effect on echinococcosis is comparable to that of albendazole at a dose of 40 mg / kg, and the therapeutic effects of Geraniin at doses of 40 mg / kg and 80 mg / kg are equivalent.

[0015] The present invention also provides a pharmaceutical composition for treating echinococcosis, comprising an active ingredient and pharmaceutically acceptable excipients, said active ingredient being Geraniin or a pharmaceutically acceptable salt or hydrate of the salt thereof.

[0016] Furthermore, the dosage form of the pharmaceutical composition is an oral dosage form.

[0017] Furthermore, the oral dosage form is a tablet, granule, powder, capsule, oral liquid, or lozenge.

[0018] The beneficial effects of this invention are as follows: The EmAGO2 protein targeted by this invention differs significantly from human AGO proteins in amino acid sequence and structural function, particularly in the substrate binding domain and cofactor interaction region. Drugs developed based on this target are less likely to interfere with the normal physiological function of the host's own AGO proteins. This reduces the risk of off-target toxicity from the target design perspective, and theoretically has lower systemic toxicity and a wider therapeutic window, thus ensuring the safety of clinical use.

[0019] This invention clarifies for the first time the application value of Geraniin, a small molecule inhibitor targeting the EmAGO2 protein of Echinococcus multilocularis, in the treatment of Echinococcus multilocularis cysts. It fills the gap in the existing technology for developing anti-Echinococcus multilocularis cyst drugs with EmAGO2 as a direct drug target, and provides a brand-new technical path for the treatment of this disease. It breaks through the technical bottlenecks of existing treatments, such as high target homology, high off-target risk, and limited effect on germinal layer stem cells that drive the unlimited proliferation of lesions.

[0020] This invention screened Germanin using computer-aided drug design technology and independently verified it using micro-thermophoresis and surface plasmon resonance techniques. The results confirmed that Germanin binds to EmAGO2 protein with a significant high affinity, with a binding affinity constant KD of 90.8 nM and an equilibrium dissociation constant KD of 14.00 nM. This clarified the molecular mechanism by which Germanin exerts its anti-hydatid effect, providing a solid theoretical basis for its subsequent drug development and clinical translation.

[0021] In vitro experimental results showed that Geraniin has a strong inhibitory activity against the protocercariae of Echinococcus multilocularis. The survival rate of the protocercariae decreased significantly in a dose-dependent manner with increasing Geraniin concentration. Its half-maximal inhibitory concentration (IC50) against the protocercariae was [value missing]. 50 The concentration was 10.27 μM. Meanwhile, Geraniin significantly inhibited the growth and development of new vesicles formed by the differentiation of protocercariae. The treated vesicles showed obvious shrinkage phenotype, and the degree of shrinkage increased significantly with increasing drug concentration, thus achieving effective inhibition of different developmental stages of Echinococcus multilocularis.

[0022] In vivo animal experiments showed that oral administration of 40 mg / kg and 80 mg / kg Germanin every 3 days for one month significantly reduced the lesion area and the number and weight of echinococcosis cysts in mice infected with Echinococcus multilocularis. The therapeutic effect was comparable to that of albendazole, a first-line clinical drug. Furthermore, the therapeutic effects of 40 mg / kg and 80 mg / kg Germanin were comparable, suggesting that lower doses can achieve ideal therapeutic effects, which is beneficial for reducing clinical drug costs and potential adverse reaction risks. There was no significant difference in body weight among the groups during treatment, further confirming the good in vivo safety of Germanin at effective therapeutic doses.

[0023] The application scheme of Geraniin in the preparation of drugs for treating echinococcosis provided by this invention provides reliable technical support for the efficient prevention and treatment of echinococcosis, lays a solid experimental foundation for the clinical application of Geraniin in the treatment of echinococcosis, and is expected to improve the current clinical dilemma of limited drugs for the treatment of echinococcosis, poor efficacy, and easy development of drug resistance with long-term use. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 Image showing the expression and localization results of EmAGO2 protein in multilocular Echinococcus larvae tissue detected by immunofluorescence staining; Figure 2 The image shows the results of micro-thermophoresis (MST) to detect the binding affinity of the small molecule inhibitor Geraniin to the EmAGO2 protein. Figure 3 The graph shows the results of surface plasmon resonance (SPR) technology to verify the specific binding of the compound to EmAGO2 protein. In the graph, A is the binding curve of DMSO solvent control with different concentrations of EmAGO2 protein, and B is the specific binding curve of Geraniin with different concentrations of EmAGO2 protein. Figure 4 The figure shows the survival rate of protoscars of multilocular Echinococcus larvae after in vitro treatment with different concentrations of Geraniin for 48 hours. Figure 5 The figure shows the morphological changes and statistical results of vesicle activity of protoscolex of multilocular Echinococcus protoscolex after 48 h of in vitro treatment with different concentrations of Geraniin. Figure 6 Figure showing the changes in body weight in mice infected with Echinococcus multilocularis during 30 days of continuous treatment with the Geraniin small molecule inhibitor; Figure 7 The images show the liver morphology and cyst weight statistics of mice infected with Echinococcus multilocularis after 30 days of treatment with the Geraniin small molecule inhibitor. The images include gross liver morphology, liver weight statistics, and Echinococcus cyst weight statistics for each group of mice. Detailed Implementation

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0028] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0029] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0030] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0031] Example 1: Validation of Geraniin's activity in targeting EmAGO2 for the treatment of multilocular echinococcosis 1. Geraniin binds to EmAGO2 with significant high affinity. 1.1 Method 1.1.1 Virtual screening of small molecule compounds targeting EmAGO2 protein The amino acid sequence of the EmAGO2 protein was retrieved and downloaded from the UniProt database, formatted into standard FASTA format, and imported into the AlphaFold official workflow. Combining homology sequence retrieval and template modeling results, a three-dimensional structural model of the EmAGO2 protein was generated. Five independent random seeds were used to construct the model, and the optimal conformation was selected based on pLDDT confidence. Energy minimization was performed using OpenMM, and stereochemical rationality was verified using MolProbity. Finally, high-confidence EmAGO2 three-dimensional structural coordinates were output.

[0032] Simultaneously, to conduct subsequent virtual screening experiments, 2D format compounds from the Bioactive CompoundLibrary Plus (HY-L001P) and Fragment Compound Library (HY-L032) were preprocessed using the LigPrep module of Schrödinger software. This preprocessing included hydrogenation, energy optimization, format conversion, desalting, and charge correction, ultimately outputting the 3D structures of the compounds. Virtual screening was then performed using the Virtual Screening Workflow module of Schrödinger software. The preprocessed compounds were imported, and molecular docking experiments were conducted using the Glide module. Precise docking was achieved through geometric and energy matching between the EmAGO2 protein and the compounds. After docking, key indicators such as the binding strength between the target and the compound, and the structural stability of the compounds were manually verified to screen candidate compounds with strong binding affinity to the EmAGO2 protein.

[0033] 1.1.2 Micro-thermophoresis (MST) technique for detecting binding affinity The specific method is as follows: Take 10 μL of each 50 nM EmAGO2 protein sample and mix thoroughly with an equal volume of serially diluted Geraniin solution (starting at 5 μM, with a total of 10 concentration gradients). Incubate at 4℃ for 30 min to allow the protein and compound to fully bind and reach equilibrium. Add all incubated samples sequentially to MST-specific capillary tubes and detect using a Monolith NT.115 instrument. Detection parameters are set as follows: temperature 25℃, excitation power 40%, automatic fluorescence intensity gain adjustment, and a standard capillary tube.

[0034] 1.1.3 Surface Plasmon Resonance (SPR) technique to verify specific binding The Germanin compound was diluted to a preset printing concentration (10 μM) and printed onto the surface of a 3D photocrosslinked chip using a Biodot™ AD1520 chip array printer. Four replicates were set for each sample to ensure experimental reliability. Four positive control points (rapamycin) were printed at the four corners of the chip as experimental references. After printing, the chip was dried in a vacuum environment and then placed in the photocrosslinking instrument for photocrosslinking reaction. After the reaction, the chip was washed sequentially with DMF (N,N-dimethylformamide), anhydrous ethanol (C2H5OH), and ultrapure water (H2O) for 15 minutes each to remove unbound impurities and residual reagents. After drying with nitrogen, the chip was assembled with a Flowcell Cover, sealed, and stored for subsequent interaction detection experiments.

[0035] EmAGO2 protein samples were diluted to five concentration gradients: 10 nM, 40 nM, 160 nM, 640 nM, and 2560 nM. PBST (pH 7.4, containing 0.1% Tween 20) was used as the flow carrier throughout the experiment, with all samples being flowed sequentially for testing. Analytes were administered in 0.5 μL increments. s -1 The flow rate is 2 μL over the chip surface; in the surface regeneration stage, Glycine-HCl solution (pH=2.0) is used as the regeneration solution, and the flow rate is set to 2 μL. s -1 The experiment involved loading compound samples with different concentration gradients in order of increasing concentration, while maintaining a flow rate of 0.5 μL. s -1 The reaction temperature was controlled at 4℃, the binding time was 600s, and the dissociation time was 360s.

[0036] 1.2 Results like Figure 1 As shown, immunofluorescence staining results confirmed that EmAGO2 was significantly highly expressed in the germinal layer cells of Echinococcus multilocularis, indicating that it may play a key role in the maintenance and proliferation of Echinococcus multilocularis stem cell lineages.

[0037] Based on the three-dimensional structure of EmAGO2 predicted by AlphaFold, this study used the Virtual ScreeningWorkflow module to perform virtual screening of a small molecule compound library. After high-throughput screening, the Glide module was used for precise molecular docking, ultimately yielding Geraniin (Catalog_NO: HY-N0472, docking score: -13.061), a small molecule compound that can form a significantly high affinity binding with EmAGO2. Its structural formula is shown below: .

[0038] like Figure 2 As shown, micro-thermophoresis (MST) was used to preliminarily verify that the binding affinity constant (KD) between Geraniin and EmAGO2 protein was 90.8 nM.

[0039] like Figure 3 As shown, further verification using surface plasmon resonance (SPR) technology confirmed that Geraniin can specifically and strongly bind to the EmAGO2 protein, with an equilibrium dissociation constant (KD) of 1.40 × 10⁻⁶. -8 M (14.00nM).

[0040] 2. Geraniin inhibits the bioactivity of protocercariae in vitro. 2.1 Method Protostomies of *Echinococcus multilocularis* larvae with isolated and purified activity ≥95% were collected and their concentration adjusted to 1.2 × 10⁻⁶ using high-glucose DMEM medium containing 10% fetal bovine serum. 4 Geraniin inhibitor concentrations were measured at 0, 1, 2, 5, 10, and 20 μM, with three replicates per well. An equal volume of DMSO was added to the solvent control group to maintain consistent concentrations across all groups. After incubation at 37°C with 5% CO2 for 48 hours, the 96-well plates were observed using PI staining combined with fluorescence microscopy to count and calculate the protocercariae survival rate. Finally, a dose-response curve was fitted using GraphPad Prism software, and the half-maximal inhibitory concentration (IC50) was calculated. 50 This was used to evaluate the activity of the Geraniin inhibitor.

[0041] 2.2 Results like Figure 4 As shown, the survival rate of protocercariae decreased significantly in a dose-dependent manner with increasing Geraniin concentration (0-20 μM), indicating that this compound possesses potent anti-protocercariae activity in vitro. The half-maximal inhibitory concentration (IC50) of Geraniin against the protocercariae of *Echinococcus multilocularis* was calculated. 50 The value was 10.27 μM.

[0042] 3. Geraniin significantly inhibited the growth and development of new vesicles formed from the differentiation of protocercariae in vitro. 3.1 Method 2000 protostomes of *Echinococcus multilocularis* with viability ≥95% were inoculated into cell culture flasks, and 10 mL of high-glucose DMEM medium (containing 10% fetal bovine serum and 1% penicillin-streptomycin) was added. The flasks were then incubated at 37°C in a 5% CO2 incubator. The medium was replaced with fresh medium every 7 days during the culture period, and the culture was continued for 3 months until the vesicles grew to a diameter of approximately 5 mm.

[0043] The cultured vesicles were collected, counted, and then seeded into groups: 50 vesicles per well were seeded into 6-well plates, and Geraniin small molecule inhibitors were added at final concentrations of 0 μM (blank control group), 5 μM, 10 μM, and 20 μM, respectively. After treatment for 48 h, the morphological changes of the vesicles in each group were observed and recorded using an inverted microscope.

[0044] 3.2 Results like Figure 5 As shown, after treatment with Geraniin, the vesicles formed by the differentiation of Echinococcus multilocularis protoscars exhibited a distinct shrunken phenotype, and the degree of shrunkenness significantly increased with increasing inhibitor concentration. These results indicate that the small-molecule inhibitor Geraniin can significantly inhibit the growth and development of Echinococcus multilocularis protoscar vesicles.

[0045] 4. In vivo validation of the efficacy of targeted EmAGO2 therapy for multilocular echinococcosis. 4.1 Establishment of a mouse model of multilocular echinococcosis via portal vein infection To further validate the efficacy of EmAGO2-targeted therapy for echinococcosis in vivo, this study used C57 / 6J mice as experimental subjects and established an echinococcosis infection model by injecting protoscolex via the portal vein. Gerbils infected with echinococcosis were euthanized by cervical dislocation and disinfected by immersion in 75% alcohol. Under aseptic conditions, protoscolex were isolated, and echinococcosis cysts were detached from the gerbil tissue. Residual tissue was removed, and the cysts were placed in pre-cooled PBS buffer containing 100 U / mL penicillin and 100 U / mL streptomycin, and washed three times. The cyst tissue was then minced with ophthalmic scissors, and the mixture was passed through an 80-mesh copper screen. After the worms settled naturally, the supernatant was discarded. This process was repeated three times until the solution was clear, and then diluted to a protoscolex suspension of 5000 worms / mL. Twelve 8-week-old C57BL / 6 mice were selected and a multilocular echinococcosis infection model was established by intravenous injection of 100 μL of suspension (containing 500 protocercariae) into the portal vein.

[0046] 4.2 Experimental Grouping and Drug Treatment 4.2.1 Experimental Grouping After successful modeling, mice infected with Echinococcus multilocularis were randomly divided into four groups: 40 mg / kg Geraniin intervention group, 80 mg / kg Geraniin intervention group, solvent treatment negative control group, and 40 mg / kg albendazole treatment positive control group.

[0047] 4.2.2 Drug Preparation First, the small molecule inhibitor Geraniin was dissolved in DMSO to prepare a stock solution with a concentration of 20 mg / mL, which was then diluted with physiological saline to a working concentration of 1 mg / mL. Albendazole and solvent control solutions were prepared using the same method.

[0048] 4.2.3 Administration method and cycle Oral administration was performed via gavage, with dosages set at 40 mg / kg albendazole, 40 mg / kg and 80 mg / kg geraniin; the solvent control group mice were administered an equal dose of physiological saline solution containing DMSO via gavage. Administered once every 3 days for 30 consecutive days.

[0049] 4.3 Data Statistics and Results Analysis After treatment, the mice were euthanized and dissected, and their body weight, liver weight, and the weight of the cysts after liver removal were recorded.

[0050] like Figure 6 As shown, there was no significant difference in body weight among the groups of mice during the treatment period, indicating that Geraniin has good in vivo safety at doses of 40 mg / kg and 80 mg / kg.

[0051] like Figure 7 As shown, compared with the solvent control group, mice treated with the small molecule inhibitor Geraniin (40 mg / kg and 80 mg / kg) exhibited significantly smaller lesion areas and a significant decrease in the number and weight of Echinococcus cysts, indicating that this small molecule inhibitor has good anti-Echinococcus multilocularis tapeworm activity. The therapeutic effects of 40 mg / kg and 80 mg / kg Geraniin were comparable, and both were on par with the efficacy of the first-line clinical drug albendazole.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. The use of Geraniin in the preparation of drugs for treating echinococcosis, characterized in that, The structural formula of Geraniin is shown below: 。 2. The application according to claim 1, characterized in that, The Geraniin targets and binds to the EmAGO2 protein of Echinococcus multilocularis, and the two bind with a significantly high affinity.

3. The application according to claim 2, characterized in that, The binding affinity constant KD of Geraniin to EmAGO2 protein is 90.8 nM, and the equilibrium dissociation constant KD is 14.00 nM.

4. The application according to claim 1, characterized in that, The aforementioned echinococcosis is caused by infection with Echinococcus multilocularis. Its characteristic pathological change is that the protoscolex continuously produces new vesicles in the host through exophytic budding reproduction, forming vesicle clusters or masses.

5. The application according to claim 1, characterized in that, The drug is in oral dosage form.

6. The application according to claim 1, characterized in that, When administering Geraniin, it should first be dissolved in DMSO, then diluted with physiological saline before administration. The dosage of Geraniin in the drug should not be less than 40 mg / kg.

7. The application according to claim 1, characterized in that, When Geraniin is administered orally at doses of 40 mg / kg or 80 mg / kg, its therapeutic effect on echinococcosis is comparable to that of albendazole at doses of 40 mg / kg, and the therapeutic effects of Geraniin at doses of 40 mg / kg and 80 mg / kg are equivalent.

8. A pharmaceutical composition for treating echinococcosis, characterized in that, It includes an active ingredient and pharmaceutically acceptable excipients, wherein the active ingredient is Geraniin or a pharmaceutically acceptable salt or hydrate of the salt thereof.

9. The pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical composition is in the form of an oral dosage form.

10. The pharmaceutical composition according to claim 9, characterized in that, The oral dosage form is tablet, granule, powder, capsule, oral liquid or lozenge.

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