CN116421590A - Application of chlorhexidine diacetate in preparing medicine for preventing or/and treating liver cancer - Google Patents

Application of chlorhexidine diacetate in preparing medicine for preventing or/and treating liver cancer Download PDF

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CN116421590A
CN116421590A CN202310701096.3A CN202310701096A CN116421590A CN 116421590 A CN116421590 A CN 116421590A CN 202310701096 A CN202310701096 A CN 202310701096A CN 116421590 A CN116421590 A CN 116421590A
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liver cancer
chlorhexidine diacetate
medicament
preventing
application
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CN116421590B (en
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周洪钟
徐勇
顾大勇
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Shenzhen Second Peoples Hospital
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
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    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

The application relates to a new application of chlorhexidine diacetate, in particular to an application of chlorhexidine diacetate in preparing medicines for preventing or/and treating liver cancer. Further, the liver cancer cell is SNU449. Compared with the traditional technology, the application has the following beneficial effects: the chlorhexidine diacetate is applied to the preparation of the medicine for preventing or/and treating liver cancer for the first time. The inventor discovers that the chlorhexidine diacetate can specifically inhibit the proliferation of liver cancer cells, and is hopeful to be a novel drug for overcoming liver cancer by inhibiting the RNA helicase DDX 17.

Description

Application of chlorhexidine diacetate in preparing medicine for preventing or/and treating liver cancer
Technical Field
The application relates to the technical field of medicines, in particular to application of chlorhexidine diacetate in preparing medicines for preventing or/and treating liver cancer.
Background
Hepatocellular carcinoma (Hepatocellular carcinoma, HCC) is abbreviated as liver cancer, which refers to malignant tumor occurring in liver, including primary liver cancer and metastatic liver cancer, and liver cancer is often referred to as primary liver cancer. Primary liver cancer is one of the most common malignant tumors in clinic, and according to the latest statistics, new liver cancer patients worldwide occupy about sixty thousand every year, and the death rate is the second highest among all tumors. Primary liver cancer can be classified into hepatocellular liver cancer, cholangiocellular liver cancer and mixed liver cancer according to cell types. The tumor forms can be classified into nodular, giant block and diffuse forms.
The treatment means of liver cancer is various, and surgery and targeted treatment exist, but the surgical treatment represented by hepatectomy is still the first choice treatment method of liver cancer at present. Currently, therapeutic drugs for liver cancer include sorafenib, lenvatinib, dorafinib, bevacizumab in combination with atilizumab, regorafenib, apatinib, cabotinib, and the like. The treatment of conventional chemotherapeutics (such as doxorubicin, fluorouracil, cisplatin, alpha-interferon and the like) has serious toxic and side effects, and can not obviously relieve diseases or prolong lives in general, and the curative effect of most other medicines is difficult to achieve. In molecular targeted therapy of liver cancer, sorafenib is the standard therapeutic means of advanced hepatocellular carcinoma at present, and a tyrosine kinase inhibitor sorafenib of a drug which can prolong the survival time of a liver cancer patient is proved to have obvious side effects. While other new targeted drug studies emerge following sorafenib, none of its overall survival rates for patients with primary treatment endpoints is better than sorafenib. The reason is that the hepatocellular carcinoma is not like the lung cancer, and has definite driving genes or biomarkers, so that the development of new medicine research and development targets for liver cancer is very difficult. In addition to immune checkpoint inhibitors, various inhibitors against various cancer targets such as various growth factor receptors, C-MET and the like are in progress, but the effective targets and inhibitors still lack in the field of liver cancer treatment as a whole, and the development of more effective anticancer drugs is urgently needed in clinic.
Chlorhexidine diacetate (Chlorhexidine diacetate) belongs to the family of biguanides and has the molecular formula C 26 H 38 Cl 2 N 10 O 4 Molecular weight 625.55, often used as a broad-spectrum antibacterial and disinfectant, and the corresponding mechanism of action involves disrupting the cell membrane of the bacteria. Has strong bactericidal effect on gram positive bacteria, gram negative bacteria and fungi, and on Pseudomonas aeruginosa, and is often used for skinSkin disinfection and wound irrigation, and can also be used for disinfecting surgical instruments. Currently, there is no study of chlorhexidine diacetate for use on hepatoma cells.
Disclosure of Invention
Based on the above, the application provides a new application of the chlorhexidine diacetate, in particular to an application of the chlorhexidine diacetate in preparing a medicament for preventing or/and treating liver cancer, and the chlorhexidine diacetate can effectively inhibit liver cancer cells and has obvious efficacy of treating the liver cancer.
The technical scheme of the application comprises the following steps:
the application of chlorhexidine diacetate in preparing medicines for preventing or/and treating liver cancer is provided.
In one embodiment, treating liver cancer comprises: inhibit proliferation of liver cancer cells.
In one embodiment, inhibiting liver cancer cell proliferation comprises inhibiting expression of DDX17 protein.
In one embodiment, the liver cancer cell is the liver cancer cell line SNU449.
In one embodiment, the medicament comprises chlorhexidine diacetate and pharmaceutically acceptable excipients.
In one embodiment, the pharmaceutical dosage form is a tablet.
In one embodiment, the pharmaceutical dosage form is a capsule.
In one embodiment, the dosage form of the medicament is an oral liquid, an oral granule or an oral powder.
In one embodiment, the pharmaceutical dosage form is an injection.
In one embodiment, the injection is a freeze-dried powder injection or an emulsion for injection.
Compared with the traditional technology, the application of the chlorhexidine diacetate in the preparation of the medicine for preventing or/and treating the liver cancer has the following beneficial effects:
the study shows that the chlorhexidine diacetate can be used as a chemotherapeutic drug for the first time, and can obviously inhibit malignant growth, panel clonality and DNA synthesis capacity of liver cancer cells (such as SNU 449). And the chlorhexidine diacetate can obviously inhibit the expression of DDX17 protein along with the increase of the concentration of the drug, and is expected to become a new generation drug for targeting DDX17 to inhibit malignant proliferation of liver cancer cells.
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In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic illustration of the structural formula of chlorhexidine diacetate of an embodiment;
FIG. 2 is a graph showing the results of an MTS assay for detecting the survival rate of chlorhexidine diacetate against SNU 449;
FIG. 3 is a graph showing experimental results of chlorhexidine diacetate on clone formation of SNU449, a hepatoma cell, in a plate clone formation experiment according to an embodiment;
FIG. 4 is a graph showing the experimental results of EDU experiments to detect the DNA synthesis ability of chlorhexidine diacetate on SNU449 of hepatoma cells in one embodiment;
FIG. 5 is a graph showing experimental results of determining the interaction affinity of chlorhexidine diacetate with DDX17 protein using surface plasmon resonance technique in one example;
FIG. 6 is a western blot plot comparing expression levels of DDX17 after treatment with chlorhexidine diacetate at different concentrations and a control group treated with DMSO in an example.
Detailed Description
In order to facilitate an understanding of the present application, a more complete description of the present application will now be provided with reference to the relevant figures. Preferred embodiments of the present application are shown in the accompanying drawings. This application may, however, be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" is at least two, such as two, three, etc., unless explicitly defined otherwise. In the description of the present application, the meaning of "several" means at least one, such as one, two, etc., unless explicitly defined otherwise.
When a range of values is disclosed herein, the range is considered to be continuous and includes both the minimum and maximum values for the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range description features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to include any and all subranges subsumed therein.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the description of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
By "pharmaceutically acceptable" is meant those ligands, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for administration to patients and commensurate with a reasonable benefit/risk ratio.
"pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. As used herein, the language "pharmaceutically acceptable carrier" includes buffers compatible with pharmaceutical administration, sterile water for injection, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. Each carrier must be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the patient. Suitable examples include, but are not limited to: (1) sugars such as lactose, glucose and sucrose; (2) Starches, such as corn starch, potato starch, and substituted or unsubstituted beta-cyclodextrin; (3) Cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) Oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) Polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) ringer's solution; (19) ethanol; (20) phosphate buffer; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.
Mode of administration
The dosage form and mode of administration of the compounds of the present application or pharmaceutical compositions thereof are not particularly limited.
Representative modes of administration include, but are not limited to: oral, intratumoral, rectal, parenteral (intravenous, intramuscular or subcutaneous) injection, and topical administration.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is admixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following ingredients: (a) Fillers or compatibilizers, for example, starch, lactose, sucrose, glucose, mannitol and silicic acid; (b) Binders, for example, hydroxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and acacia; (c) humectants, e.g., glycerin; (d) Disintegrants, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) a slow solvent, such as paraffin; (f) an absorption accelerator, e.g., a quaternary amine compound; (g) Wetting agents, such as cetyl alcohol and glycerol monostearate; (h) an adsorbent, for example, kaolin; and (i) a lubricant, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate, or mixtures thereof.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or tinctures. In addition to the active compound, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, propylene glycol, 1, 3-butylene glycol, dimethylformamide and oils, in particular, cottonseed, groundnut, corn germ, olive, castor and sesame oils or mixtures of these substances. In addition to these inert diluents, the compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Such as suspensions, may contain suspending agents as, for example, particularly ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar or mixtures of these substances.
Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous or nonaqueous carriers, diluents, solvents or excipients include water, ethanol, polyols and suitable mixtures thereof.
Dosage forms for topical administration include ointments, powders, patches, sprays and inhalants. Is prepared by mixing the active ingredient under aseptic condition with pharmaceutically acceptable carrier and any preservative, buffer or propellant as required.
The application provides an application of chlorhexidine diacetate in preparing a medicament for preventing or/and treating liver cancer.
Optionally, treating liver cancer comprises: inhibit proliferation of liver cancer cells.
Further alternatively, inhibiting proliferation of a hepatoma cell comprises inhibiting expression of DDX17 protein.
Optionally, the liver cancer cell is a liver cancer cell line SNU449.
Optionally, the medicament comprises chlorhexidine diacetate and pharmaceutically acceptable excipients.
It will be appreciated that the type of adjuvant selected, the amount of adjuvant used, etc. will vary depending on the dosage form of the drug. Chlorhexidine diacetate can be combined with proper auxiliary materials to prepare medicaments (such as liquid, semisolid and solid) with different forms, and correspondingly different dosage forms are formed.
Optionally, the dosage form of the medicament is a tablet.
It is understood that in the present application, the tablet is a tablet or a special-shaped tablet solid preparation obtained by uniformly mixing and pressing a drug and an auxiliary material, and mainly comprises an oral common tablet, and also comprises a buccal tablet, a sublingual tablet, an oral patch and the like. The tablets may be coated for stability, to mask unpleasant odors of the drug, to improve the appearance of the tablet, etc.
In one embodiment, the tablet is a coated tablet.
Optionally, the dosage form of the medicine is a capsule.
It is understood that in the present application, the capsule refers to a solid preparation prepared by filling a medicine or a proper auxiliary material into a hollow hard capsule or sealing a soft capsule material, and can be divided into a hard capsule and a soft capsule (capsule pill), which are mainly used for oral administration, and are also a solid preparation with wide clinical application.
Optionally, the dosage form of the medicine is oral liquid, oral granule or oral powder.
In one embodiment, the pharmaceutical dosage form is an oral granule.
It is understood that in the present application, the oral granule refers to a dry granular preparation with a certain granularity prepared by mixing a raw material medicine and a proper auxiliary material, and is a commonly used oral solid dosage form. The sum of the coarse particles larger than the first sieve and the fine particles smaller than the fifth sieve in the granules is not more than 15% unless otherwise specified. The granule can be directly swallowed, or can be infused into water for drinking.
Optionally, the medicament is in the form of injection.
It is understood that in this application, injectable formulations are intended to mean sterile solutions (including emulsions and suspensions) for injection into the body, as well as sterile powders or solutions in concentration for constitution as a solution or suspension immediately prior to use.
In one embodiment, the injection is a freeze-dried powder injection.
In one embodiment, the injection is an emulsion for injection.
In the above, the embodiments of the present application are merely illustrative of the types of "dosage forms", and it is to be understood that these are not specific limitations of "dosage forms", and chlorhexidine diacetate may be prepared into other suitable pharmaceutically acceptable dosage forms in addition to the several dosage forms of "tablet", "capsule", "oral liquid" and "injection" illustrated in the present application.
The following examples are further offered to illustrate, but not to limit, the materials used in the examples are commercially available, and chlorhexidine diacetate as described in the examples herein are commercially available, and the processes used are commercially available, and are routine to those skilled in the art.
The following are specific examples.
Example 1
(1) Preparation of cells
Human hepatoma cell SNU449 was purchased from Jiniou Biocompany, guangzhou;
the method for culturing the human liver cancer cell SNU449 comprises the following steps: preparing mixed culture medium comprising DMEM culture medium+10% Fetal Bovine Serum (FBS) +1% penicillin/streptomycin double antibody (P/S), adding the cells into the prepared mixed culture medium, and placing at 37deg.C and 5% CO 2 Culturing in a cell culture box, observing cell fullness of the culture dish after 48-72h, and waiting for finenessSubculturing is performed when the cells grow to 90% -100%.
(2) Effect of chlorhexidine diacetate (Chlorhexidine diacetate) on proliferation of hepatoma cell SNU449
The liver cancer cells SNU449 were treated with chlorhexidine diacetate (15. Mu.M), and then examined for growth at four time points of 0h, 24h, 48h, and 72h, respectively, using MTS assay.
The results in conjunction with fig. 2 show that chlorhexidine diacetate significantly reduced the growth of liver cancer cells SNU449 (P < 0.05) after 72h incubation with 15 μm chlorhexidine diacetate relative to the Dimethylsulfoxide (DMSO) -treated control.
(3) Effect of chlorhexidine diacetate on the clonality of liver cancer cell SNU449
The liver cancer cells SNU449 are inoculated into six holes, the cell number is 0.1-0.3 k cells/hole, the liver cancer cells are cultured for 10 days according to the conventional method for culturing the liver cancer cells, then 15 mu M chlorhexidine diacetate is used for 2-3 days, after the culture medium is removed, the liver cancer cells are washed by 1 XPBS, 1ml of methanol is added for 30min, 0.1% crystal violet is used for dyeing, after 60min, the crystal violet is removed, the liver cancer cells are washed by 1 XPBS, the liver cancer cells are photographed and counted after airing, and the control group is treated as above, but the chlorhexidine diacetate is not added.
In conjunction with the results of fig. 3, it was shown that the panel clonality of liver cancer cells SNU449 (P < 0.05) was significantly reduced after treatment with chlorhexidine diacetate relative to DMSO-treated control.
(4) Effect of chlorhexidine diacetate on the DNA synthesis ability of liver cancer cell SNU449
Liver cancer cells SNU449 were inoculated into six wells containing slides, and chlorhexidine diacetate (15. Mu.M) was added the next day for 2-3 days and treated with EDU kit (Biyun, C0085S) and the effect of chlorhexidine diacetate on the DNA synthesis capacity of liver cancer cells SNU449 was observed under a fluorescence microscope.
The results in connection with fig. 4 show that DNA synthesis capacity of liver cancer cell SNU449 (P < 0.05) can be significantly reduced after treatment with chlorhexidine diacetate compared to the control group without chlorhexidine diacetate.
(5) Chlorhexidine diacetate has interaction affinity with DDX17 protein
RNA helicase DDX17 is DEAD-box17 (DDX 17) which is one of the important members of the DDX family of RNA helicases, the core region of which comprises 9 conserved motifs (Q, I, ia, ib, II-VI). DDX17 is characterized by a conserved motif Asp-Glu-Ala-Asp (DEAD) a DEAD box protein that involves many cellular processes of RNA secondary structure alterations such as translation initiation, nuclear and mitochondrial splicing, ribosomal and splice assembly. The gene encodes a DEAD box protein, which is an ATPase activated by multiple RNAs, but not dsDNA, and can be involved in almost all processes related to RNA metabolism, such as transcription to translation. Play an important role in the growth of cancer. The research shows that the expression of DDX17 is obviously increased in various tumors, including liver cancer, lung cancer, breast cancer, prostate cancer and the like. In addition, several studies have shown that DDX17 can promote malignant proliferation and migration invasion of liver cancer.
A DDX17 protein-FDA marketed compound interaction determination model is established by utilizing a Surface Plasmon Resonance (SPR) technology, 1729 compounds in the FDA marketed drug library are divided into 36 groups of mixtures according to about 50 compounds/component, SPR single concentration point (10 mu M) screening is carried out, and 4 groups of compounds are selected according to the descending order of RU values. The 4 groups of compounds were then subjected to single concentration (10. Mu.M) SPR sequencing 200 in total, ordered according to decreasing RU values. Finally, the top-ranked compounds are set to multiple concentrations for SPR test to obtain affinity data KD and kinetic numbers Kd and ka. Compounds with higher binding affinity to DDX17 were screened based on binding pattern analysis. A DDX17 protein-compound interaction assay model was established using Surface Plasmon Resonance (SPR).
The results in FIG. 5 show that chlorhexidine diacetate has a higher interaction affinity with DDX17 protein.
(6) Chlorhexidine diacetate inhibiting RNA helicase DDX17 expression level
The method is characterized in that chlorhexidine diacetate is used for treating liver cancer cells SNU449, and the influence of the chlorhexidine diacetate under the action of different concentrations on the expression level of DDX17 protein is detected by utilizing a WB experiment, wherein the specific operation process is as follows:
the liver cancer cell SNU449 is inoculated in six holes, the next day is treated by 3.75 mu M, 7.5 mu M and 15 mu M chlorhexidine diacetate respectively for 2-3 days, then DDX17 protein is cracked, concentration is measured, SDS polyacrylamide gel (SDS-PAGE) is configured, electrophoresis, membrane transfer, sealing, primary anti-incubation, secondary anti-incubation and development are carried out.
The results of fig. 6 show that 15 μm chlorhexidine diacetate inhibited DDX17 most strongly as the drug concentration of chlorhexidine diacetate increased compared to DMSO-treated control. From the analysis of the results, chlorhexidine diacetate can be used as a small molecular compound inhibitor of DDX17 protein and can inhibit malignant proliferation of liver cancer cells.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples merely represent a few embodiments of the present application, which are described in more detail and are not to be construed as limiting the scope of the invention. It should be noted that it would be apparent to those skilled in the art that various modifications and improvements could be made without departing from the spirit of the present application, which would be within the scope of the present application. Accordingly, the scope of protection of the present application is to be determined by the claims appended hereto.

Claims (10)

1. The application of chlorhexidine diacetate in preparing medicines for preventing or/and treating liver cancer is provided.
2. Use of chlorhexidine diacetate according to claim 1 for the manufacture of a medicament for the prevention or/and treatment of liver cancer, wherein treating liver cancer comprises: inhibit proliferation of liver cancer cells.
3. Use of chlorhexidine diacetate according to claim 2 for the manufacture of a medicament for the prevention or/and treatment of liver cancer, wherein inhibiting proliferation of liver cancer cells comprises inhibiting expression of DDX17 protein.
4. The use of chlorhexidine diacetate according to claim 3 for the preparation of a medicament for preventing or/and treating liver cancer, wherein the liver cancer cell is the liver cancer cell line SNU449.
5. Use of chlorhexidine diacetate according to any of claims 1 to 4 for the manufacture of a medicament for the prevention or/and treatment of liver cancer, characterized in that the medicament comprises chlorhexidine diacetate and pharmaceutically acceptable excipients.
6. The use of chlorhexidine diacetate according to claim 5 for the manufacture of a medicament for the prevention or/and treatment of liver cancer, wherein the dosage form of the medicament is a tablet.
7. The use of chlorhexidine diacetate in the preparation of a medicament for preventing or/and treating liver cancer according to claim 5, wherein the dosage form of the medicament is a capsule.
8. The use of chlorhexidine diacetate in the preparation of a medicament for preventing or/and treating liver cancer according to claim 5, wherein the dosage form of the medicament is oral liquid, oral granule or oral powder.
9. The use of chlorhexidine diacetate in the preparation of a medicament for preventing or/and treating liver cancer according to claim 5, wherein the dosage form of the medicament is an injection.
10. The use of chlorhexidine diacetate in the preparation of a medicament for preventing or/and treating liver cancer according to claim 9, which is characterized in that the injection is a freeze-dried powder injection or an emulsion for injection.
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