Medical use of compound Pladienolide B as a ricin toxin protectant

Abstract

The present invention discloses the medical use of the compound Pladienolide B as a ricin toxin protection agent. For the first time, the present invention creatively discovers and experimentally proves that the compound Pladienolide B has the effect of effectively inhibiting the toxicity of ricin toxin. The present invention provides a new idea and strategy for the research and development of ricin toxin-related drugs, and has good clinical application prospects and important translational significance.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the medical use of the compound Pladienolide B as a ricin toxin protectant. Background Art

[0002] Ricin is a plant glycoprotein extracted from castor beans and is a deadly and highly toxic biological toxin. Ricin consists of two polypeptide chains, A and B, which are connected by a disulfide bond. The toxin B chain contains two galactose or galactose residue binding sites, which can bind to the galactose residue-containing receptors on the cell surface and enter the cytoplasm through endocytosis to exert its toxic effect. Although the current research on the ricin vaccines Rivax® and RVEcTM is progressing well and monoclonal antibodies show obvious effects in neutralizing ricin, so far, no vaccine or monoclonal antibody has been clinically approved and used. Currently, the clinical treatment for ricin poisoning can only rely on symptomatic treatment, and in severe cases, plasma exchange is even required to remove ricin from the body. In addition, the production process of vaccines and antibody drugs is relatively cumbersome, the cost is high, and there are certain requirements for storage methods, which also limits the popularization and application of macromolecular ricin drugs to a certain extent.

[0003] Small molecule inhibitor drugs have good cell membrane permeability and can exert their pharmacological effects both inside and outside cells. In the treatment of ricin poisoning, small molecule ricin inhibitors have relatively broad application prospects. However, although the structure of ricin has been relatively clearly analyzed and there are many clear studies on its druggable targets, the small molecule inhibitors developed for the functional domains of ricin have not yet achieved anti-toxic activities comparable to those of monoclonal neutralizing antibodies. In addition, the poor solubility and large side effects of some small molecule compounds also limit their further research as therapeutic drugs. Although the currently developed small molecule inhibitors have limited pharmacological effects, small molecule drugs are easier to develop as drugs compared to macromolecular vaccines and antibodies. In addition, with the progress and maturity of technologies such as artificial intelligence-assisted drug design and pharmacological effect evaluation, technology empowerment has greatly improved the research and development efficiency of small molecule drugs, and developing more efficient small molecule ricin inhibitors has once again become a hot research direction for combating ricin.

[0004] Currently, although there are some research directions for ricin poisoning, there is still a lack of effective treatment drugs. The existing treatment methods mainly focus on symptomatic supportive treatment, such as maintaining water and electrolyte balance and anti-shock treatment. However, these methods have limited effects on reducing the core toxicity of ricin. Therefore, developing a drug that can effectively combat the toxicity of ricin has important practical significance and clinical needs. Summary of the Invention

[0005] In view of this, in order to overcome the above-mentioned technical problems existing in the current field, the purpose of the present invention is to provide the medical use of compound Pladienolide B as an anti-ricin toxin protectant. The present invention has creatively discovered and experimentally confirmed for the first time that compound Pladienolide B has the effect of effectively inhibiting the toxicity of ricin toxin, providing a new idea and strategy for the research and development of anti-ricin toxin related drugs, and having good clinical application prospects.

[0006] The present invention adopts the following technical solutions to achieve the above-mentioned invention purpose:

[0007] The first aspect of the present invention provides the use of Pladienolide B or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereoisomers, solvates, crystal forms or derivatives thereof in the preparation of anti-ricin toxin drugs, and the structural formula of the said Pladienolide B is shown in formula (I):

[0008]

[0009] Formula (I).

[0010] Furthermore, the said Pladienolide B has an anti-ricin toxin toxicity effect.

[0011] Furthermore, the said drug also contains pharmaceutically acceptable excipients and / or adjuvants.

[0012] Furthermore, the said pharmaceutically acceptable excipients and / or adjuvants are diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers and / or disintegrants.

[0013] Furthermore, the dosage form of the said drug is solution, sustained-release agent, suspension, granule, tablet, capsule, powder, emulsion, syrup or drop.

[0014] In the present invention, the said Pladienolide B is the main analogue of the macrolide family isolated from Streptomyces, and its corresponding Chinese name is pladienolide B. Pladienolide B is a highly efficient inhibitor of hypoxia signaling and cancer cell proliferation. Currently, there is no research or report on the anti-ricin toxin toxicity effect of Pladienolide B. Its corresponding CAS number is 445493-23-2, the molecular formula is C 30 H 48 O8, the molecular weight is 536.70, and the structural formula is shown in the above formula (I). The present invention has no special limitation on the specific source of the said Pladienolide B, and those skilled in the art can obtain it through conventional channels.

[0015] In some embodiments, the pharmaceutically acceptable salt refers to the pharmaceutically acceptable salt of Pladienolide B. Specifically, the pharmaceutically acceptable salt of Pladienolide B refers to the salt form obtained by salifying Pladienolide B and suitable for use in pharmaceutical formulations and clinical applications. The salts used in the salification process include, but are not limited to: inorganic acid salts (e.g., hydrochloride, sulfate, phosphate), organic acid salts (e.g., citrate, maleate, tartrate), and these salts are suitable for contact with patients within the scope of sound medical judgment and will not produce undue toxicity, irritation, allergic reactions, etc.

[0016] In some embodiments, examples of the pharmaceutically acceptable salts of Pladienolide B include, but are not limited to: salts having (as counterions) alkali metal ions such as Na + , Li + or K + , or salts having alkaline earth metal ions such as Ca 2+ or Mg 2+ , or salts having any other pharmaceutically acceptable metal ions such as Zn 2+ or Al 3+ ; or pharmaceutically acceptable salts formed with organic bases such as diethanolamine, ethanolamine, N-methylglucosamine, triethanolamine or tromethamine.

[0017] In some embodiments, pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali metals and alkaline earth metal hydroxides or organic amines. Examples of metals used as cations are magnesium, potassium, sodium, calcium, etc. Examples of suitable amines are N,N'-dibenzylethylenediamine, diethanolamine, chloroprocaine, choline, ethylenediamine, N-methylglucosamine or procaine.

[0018] In some embodiments, the base addition salts of acidic compounds can be prepared by the following method: contacting the free acid form with a sufficient amount of the required base in a conventional manner to form the salt. The free acid can be regenerated by contacting the salt form with an acid and then separating the free acid in a conventional manner.

[0019] In some embodiments, pharmaceutically acceptable salts may include cations based on alkali metals and alkaline earth metals, such as sodium, potassium, calcium, lithium, magnesium, etc., as well as non-toxic ammonium, quaternary ammonium and amine cations, including but not limited to: ammonium, tetramethylammonium, methylamine, dimethylamine, tetraethylammonium, trimethylamine, triethylamine, ethylamine, etc. Also included are salts of amino acids, such as gluconate, arginine salt, galacturonate, etc.

[0020] In some embodiments, the hydrate refers to a compound obtained by combining the compound of the present invention (Pladienolide B) with water. Generally, the number of water molecules contained in the hydrate of the compound is determined by the ratio to the number of molecules of the compound in the hydrate. Therefore, the hydrate of the compound can be represented by, for example, the general formula R·xH2O, where R is the compound (Pladienolide B) and x is a number greater than 0.

[0021] In some embodiments, the solvate refers to a solvate addition form of a compound containing a stoichiometric or non-stoichiometric amount of a solvent, including any solvated form of the compound of the present invention (Pladienolide B). Conventional solvents include, but are not limited to: water, ethanol, acetic acid, methanol, DMSO, THF, diethyl ether, etc. The compounds described herein can be prepared, for example, in crystalline form and can be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include stoichiometric solvates and non-stoichiometric solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0022] In some embodiments, the crystalline form refers to the crystalline form of Pladienolide B. Specifically, the crystalline form of Pladienolide B refers to the specific lattice structure and arrangement formed when Pladienolide B transforms from a solution or molten state into a crystal. In the crystal, Pladienolide B molecules are arranged in a specific pattern in three-dimensional space through intermolecular forces (such as hydrogen bonds, van der Waals forces, etc.) to form a lattice. Different crystallization conditions (such as solvents, temperature, crystallization rate, etc.) will result in differences in the molecular arrangement, thus producing different lattice structures. For example, in certain solvents, the molecules may be arranged in a closely packed manner to form a compact lattice; while under other conditions, there may be larger voids between molecules, forming a loose lattice.

[0023] In some embodiments, the derivative refers to a Pladienolide B derivative. Any modified Pladienolide B obtained by modifying Pladienolide B falls within the protection scope of the present invention. Exemplarily, the Pladienolide B derivatives include, but are not limited to: nanoparticles-modified Pladienolide B, liposome-modified Pladienolide B, exosomes encapsulating Pladienolide B, micelles encapsulating Pladienolide B, protein microspheres encapsulating Pladienolide B, or Pladienolide B modified in other forms.

[0024] In some embodiments, the anti-ricin drug refers to a drug for treating, preventing, alleviating, and / or improving diseases or symptoms related to ricin poisoning.

[0025] The second aspect of the present invention provides a pharmaceutical composition.

[0026] Furthermore, the pharmaceutical composition comprises an effective amount of Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form, or derivative thereof as described in the first aspect of the present invention.

[0027] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient and / or vehicle.

[0028] In the present invention, the pharmaceutically acceptable excipients and / or vehicles are described in detail in Remington's Pharmaceutical Sciences (19th ed, 1995). These substances are used as needed to assist in the stability of the drug or to enhance the activity of the active ingredient (i.e., Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form, or derivative thereof as described above in the present invention). Such substances include, but are not limited to: diluents, surfactants, humectants, binders, fillers, disintegrants, adsorption carriers, lubricants, stabilizers, bactericides, buffers, isotonic agents, chelating agents, pH control agents. The pharmaceutical composition thus formulated can be administered by any suitable route of administration known to those skilled in the art as needed.

[0029] In some embodiments, the pharmaceutically acceptable excipient and / or vehicle may additionally contain liquids such as water, physiological saline, glycerol, and ethanol.

[0030] In some embodiments, the pharmaceutical composition may further comprise other anti-ricin drugs. In the present invention, there are no particular limitations on the other anti-ricin drugs, and those skilled in the art can make routine selections according to actual needs. Exemplarily, the other anti-ricin drugs include, but are not limited to: monoclonal antibody drugs against ricin, vaccine drugs against ricin, other small molecule inhibitors against ricin, traditional Chinese medicine extracts against ricin, etc.

[0031] The third aspect of the present invention provides a pharmaceutical preparation.

[0032] Furthermore, the pharmaceutical preparation comprises the pharmaceutical composition described in the second aspect of the present invention.

[0033] Furthermore, the dosage form of the pharmaceutical preparation is an enteral dosage form or a parenteral dosage form.

[0034] Furthermore, the enteral dosage form is a solution, granule, tablet, capsule, suspension, powder, sustained-release preparation, effervescent agent, emulsion, syrup or drop;

[0035] The parenteral dosage form is an injection dosage form, a respiratory tract dosage form, a cavity dosage form, a mucosal dosage form or a skin dosage form.

[0036] In some embodiments, the dosage form of the pharmaceutical preparation is any one of an oral preparation, an injection preparation and an inhalation preparation. Among them, the oral preparation includes tablets, capsules and granules; the injection preparation includes solution-type injections and suspension-type injections; the inhalation preparation includes aerosols and powder aerosols.

[0037] In some embodiments, when the pharmaceutical preparation is an oral preparation, it contains Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof, and pharmaceutically acceptable excipients, and the excipients include but are not limited to: fillers, disintegrants, lubricants, binders. Among them, the filler is selected from one or more of starch, lactose and microcrystalline cellulose; the disintegrant is selected from one or more of sodium carboxymethylcellulose cross-linked, hypromellose phthalate and polyvinylpyrrolidone cross-linked; the lubricant is selected from one or more of magnesium stearate, talc and colloidal silicon dioxide; the binder is selected from one or more of hypromellose, polyvinylpyrrolidone and starch paste.

[0038] In some embodiments, when the pharmaceutical preparation is an injection preparation, its solvent is one or more of water for injection, normal saline and 5% glucose injection, and excipients such as pH regulators, osmotic pressure regulators and antioxidants can be added as needed. Among them, the pH regulator is selected from one or more of hydrochloric acid, sodium hydroxide and citric acid-sodium citrate buffer; the osmotic pressure regulator is selected from one or more of sodium chloride, glucose and mannitol; the antioxidant is selected from one or more of sodium sulfite, sodium metabisulfite and sodium thiosulfate.

[0039] In some embodiments, when the pharmaceutical preparation is an inhalation preparation, it contains Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof, and suitable excipients such as propellants, cosolvents and stabilizers. The propellant is selected from one or more of tetrafluoroethane, heptafluoropropane and carbon dioxide; the cosolvent is selected from one or more of ethanol and propylene glycol; the stabilizer is selected from one or more of oleic acid and lecithin.

[0040] In some embodiments, suitable modes of administration of the pharmaceutical composition or pharmaceutical preparation of the present invention include any of the various methods and delivery systems known to those skilled in the art for physically introducing the pharmaceutical composition or pharmaceutical preparation of the present invention into a subject, including but not limited to: oral administration, topical administration, parenteral administration, administration by inhalation spray, rectal administration, nasal administration, buccal administration, or administration through an implanted reservoir device, etc.

[0041] In some embodiments, when actually using the pharmaceutical composition or pharmaceutical preparation provided by the present invention, its dosing regimen and dosage regimen can be selected according to various factors, including the type, species, age, weight, gender of the subject and the type of disease being treated; the severity of the disease being treated; the route of administration; the renal and liver functions of the patient; and the specific compound used or other forms of the compound. One dosing and / or dosage regimen can be used, such as preventing a disease, inhibiting (fully or partially) a disease, or arresting the development of the disease. In a specific embodiment of the present invention, the disease refers to a disease related to ricin toxin poisoning.

[0042] Those skilled in the art can understand that although the pharmaceutical composition or pharmaceutical preparation mentioned above in the present invention may further contain pharmaceutically acceptable excipients and / or adjuvants, when the Pladienolide B or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof are used as drugs for humans or animals, they can also be administered in their own form, that is, the present invention can be achieved without adding any of the above-mentioned pharmaceutically acceptable excipients and / or adjuvants.

[0043] The fourth aspect of the present invention provides a method for in vitro non-therapeutically inducing cells to resist ricin toxin.

[0044] Furthermore, the method includes: treating a system in need thereof with the Pladienolide B or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof described in the first aspect of the present invention.

[0045] In some embodiments, the present invention places no particular limitation on the system in need thereof. Exemplarily, the system includes a cell system, subcellular system, tissue system or organ system in need thereof.

[0046] In addition, the present invention also provides a method for treating, preventing, alleviating, and / or improving diseases or symptoms associated with ricin toxin poisoning, said method comprising: administering to a subject in need thereof an effective amount of Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form, or derivative thereof, pharmaceutical composition, or pharmaceutical formulation as described above.

[0047] In some embodiments, the diseases or symptoms associated with ricin toxin poisoning include the following aspects: (1) Digestive system: Ricin toxin stimulates the gastrointestinal mucosa, causing severe nausea and vomiting. Excessive vomiting can lead to dehydration and electrolyte disorders. At the same time, patients will experience severe abdominal pain and diarrhea symptoms. In severe cases, it can cause damage and bleeding of the intestinal mucosa, leading to diseases such as enteritis. (2) Cardiovascular system: The toxin damages vascular endothelial cells, increasing vascular permeability. The fluid components in the blood leak into the tissue space, causing edema. For example, pulmonary edema can lead to dyspnea; vascular damage may also cause hypotension, which can develop into shock in severe cases, endangering life. In addition, heart function may also be affected, resulting in diseases such as arrhythmia and heart failure. (3) Nervous system: Poisoned patients will experience headache and dizziness symptoms. In severe cases, it can lead to convulsions, abnormal discharge of brain neurons, and then coma. (4) Urinary system: The kidneys, as important excretory organs, are also attacked by ricin toxin. The toxin damages the filtration and excretory functions of the kidneys, resulting in renal insufficiency, hematuria, proteinuria, and the body's metabolic wastes cannot be excreted normally. (5) Respiratory system: If it is inhalation ricin toxin poisoning, it will directly stimulate the respiratory tract, causing cough and chest pain. Airway inflammation and edema will lead to dyspnea, which can develop into respiratory failure in severe cases, making the body unable to obtain sufficient oxygen supply.

[0048] In the present invention, the effective amount refers to an amount having a prophylactic or therapeutic effect or an amount required to produce a prophylactic or therapeutic effect in a subject. For example, a pharmaceutically prophylactically or therapeutically effective amount refers to the amount of a drug required to produce the desired prophylactic or therapeutic effect, and the prophylactic or therapeutic effect can be reflected by the results of clinical trials, model animal studies, and / or in vitro studies. The pharmaceutically effective amount depends on several factors, including but not limited to: characteristic factors of the treatment subject (such as height, weight, gender, age, and medication history), type of the disease suffered, and severity of the disease suffered.

[0049] In the present invention, the treatment and / or prevention refers to the medical management of a patient for the purpose of preventing, curing, ameliorating or stabilizing a disease, pathological condition or disorder. This term includes active therapies, i.e., therapies specifically aimed at ameliorating a disease, pathological condition or disorder, and also includes etiological therapies, i.e., therapies aimed at removing the cause of the relevant disease, pathological condition or disorder. In addition, the treatment and / or prevention also includes palliative therapies, i.e., therapies designed to relieve symptoms rather than cure a disease, pathological condition or disorder; this term also includes prophylactic therapies, i.e., therapies aimed at minimizing or partially or completely suppressing the development of the relevant disease, pathological condition or disorder; and supportive therapies, i.e., therapies used to supplement another specific therapy aimed at ameliorating the relevant disease, pathological condition or disorder.

[0050] In the present invention, the subjects include, but are not limited to: humans (i.e., males or females of any age group, such as: pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults or elderly adults)) and / or non-human animals, such as: mammals, such as: primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats and / or dogs. In some embodiments, the subject is a non-human animal. In some embodiments, the subject is a human.

[0051] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0052] The present invention discloses for the first time a new use of Pladienolide B in anti-ricin, and through experiments, it is confirmed that the compound Pladienolide B has the effect of effectively inhibiting the toxicity of ricin. The present invention provides a new idea and strategy for the research and development of anti-ricin related drugs, and has good clinical application prospects and important translational significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 Effects of cells treated with different doses of Pladienolide B on the sensitivity to ricin;

[0054] Figure 2Effect of Pladienolide B on the sensitivity of cells to ricin at different times. Among them, Figure A: Survival curves of cells treated with different concentrations of ricin for 48 h in DMSO / untreated cells with Pladienolide B; Figure B: Survival curves of cells in each group treated with different concentrations of ricin for 48 h after pretreatment with DMSO / Pladienolide B for 6 h; Figure C: Survival curves of cells in each group treated with different concentrations of ricin for 48 h after pretreatment with DMSO / Pladienolide B for 12 h; Figure D: Survival curves of cells in each group treated with different concentrations of ricin for 48 h after pretreatment with DMSO / Pladienolide B for 24 h. Detailed implementation mode

[0055] The present invention will be further described below in conjunction with specific embodiments. The following specific embodiments are only used to explain the present invention and should not be construed as a limitation of the present invention. Those of ordinary skill in the art can understand that: various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and purposes of the present invention. The scope of the present invention is defined by the claims and their equivalents. The experimental consumables, reagents, and raw materials used in the present invention are easily obtained by those of ordinary skill in the art. Unless otherwise specified, they can all be obtained from commercial sources. The experimental methods without specific conditions described in the present invention are usually carried out under conventional conditions or according to the conditions recommended by the manufacturers. In particular, the following embodiments are only used to illustrate the present invention and should not limit the scope of the present invention in any way. It should be noted that the experimental conditions and results described in the following embodiments are only used to illustrate the present invention and should not and will not limit the present invention described in detail in the claims.

[0056] Example 1 Pladienolide B induces cells to be dose-dependent against ricin

[0057] 1. Experimental method

[0058] CCK-8 method was used to detect cell viability: Hela cells were pretreated with different doses of Pladienolide B for 24 h. Passage to 96-well plates. After the cells adhered, ricin with concentrations of 25, 12.5, 6.25, 3.12, 1.56, 0.78, 0.39, 0.195, 0.048, 0.024, 0.012, 0.006, 0.003, 0.0015, 0 ng·mL -1DMEM medium without serum, with 3 replicate wells set for each concentration (n = 3). After treating with ricin for 48 h, 10 μL of CCK-8 reagent was added to each well, and the reaction was carried out at 37 °C for 2 h. The absorbance was measured using an enzyme-linked immunosorbent assay (ELISA) reader at a wavelength of 450 nm. According to the formula: cell survival rate = [1 - (experimental well - control well) / (control well - blank well)] × 100%, the cell survival rate of each concentration experimental well was calculated, and the survival curve was fitted and plotted.

[0059] 2. Experimental results

[0060] In this example, the anti-toxic efficacy of Pladienolide B was evaluated. Specifically, cells were pretreated with different doses of Pladienolide B for 24 h, and then treated with different concentrations of ricin for 48 h, and the cell viability levels of each group were detected. As can be seen from Figure 1 the results shown, pretreatment with 1 nM Pladienolide B could make cells have a relatively obvious ricin tolerance effect. With the increase in the treatment concentration of Pladienolide B, the ability of cells to resist ricin, especially to tolerate high concentrations of ricin, gradually increased, suggesting that the effect of Pladienolide B in inducing cells to resist ricin was dose-dependent. Among them, when cells were pretreated with 100 nM Pladienolide B, they showed a completely tolerant phenotype to 100 ng / mL ricin, while the cell survival rate of the control group was only 7%. The above results indicate that Pladienolide B can effectively induce cells to resist ricin and has a dose-dependent relationship.

[0061] Example 2 Pladienolide B induces time-dependent resistance of cells to ricin

[0062] 1. Experimental method

[0063] In this example, it was further explored whether different pretreatment times of Pladienolide B affected the anti-toxic phenotype of cells induced by it. The pretreatment time of 100 nM Pladienolide B on cells was set to 0, 6, 12, 24 h, and the specific method for detecting cell viability was as described in the experimental method of Example 1 above.

[0064] 2. Experimental results

[0065] Figure 2 A shows the sensitivity of normal cells to different concentrations of ricin (cells not treated with Pladienolide B); when the pretreatment time of Pladienolide B was 6 h, the cell survival curve began to show a certain rightward shift trend, and its IC 50Increased from 0.19 ng / mL to 0.40 ng / mL, showing an approximately 2-fold increase ( Figure 2 B); when the pretreatment time of Pladienolide B was extended to 12 h, the sensitivity of cells to ricin was significantly reduced, and approximately 50% of the cells still survived under the treatment condition of high-concentration (100 ng / mL) ricin ( Figure 2 C); consistent with the previous results, when the pretreatment time of Pladienolide B was as long as 24 h, ricin had almost no killing effect on the cells ( Figure 2 D). The above results suggest that the anti-toxic effect of Pladienolide B induced in cells has a certain time-dependence.

[0066] The experimental results of the above examples show that Pladienolide B has an effect of effectively inhibiting the toxicity of ricin, can effectively induce cells to resist the toxic effect of ricin, and has a certain dose-dependence and time-dependence.

Claims

1. Use of pladienolide B or a pharmaceutically acceptable salt thereof in the preparation of an anti-ricin drug, wherein the structural formula of pladienolide B is shown as formula (I): Formula (I).

2. The application according to claim 1, characterized in that Pladienolide B has an anti-ricin toxic effect.

3. The application according to claim 1, characterized in that, The drug further comprises a pharmaceutically acceptable excipient.

4. The application according to claim 3, characterized in that The pharmaceutically acceptable excipient is a diluent, a binder, a surfactant, a humectant, an adsorption carrier, a lubricant and / or a disintegrant.

5. The application according to claim 1, wherein The dosage form of the drug is a solution, a sustained-release agent, a suspension, a granule, a tablet, a capsule, a powder, an emulsion, a syrup or a drop.

6. A method for non-therapeutically inducing cells to counteract ricin in vitro, characterized in that, The method comprises: treating a system in need with pladienolide B or a pharmaceutically acceptable salt thereof as described in claim 1.

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