Medical application of compound Pladienolide B as anti-ricin protective agent

Abstract

The invention discloses a medical application of a compound Pladienolide B as an anti-ricin protective agent, creatively discovers and verifies that the compound Pladienolide B has an effect of effectively inhibiting the toxicity of ricin for the first time through experiments, and provides a brand new thought and strategy for research and development of anti-ricin related drugs. Good clinical application prospects and important transformation significance are realized.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to the medical use of a compound Pladienolide B as an anti-ricin toxin protective agent. Background Art

[0002] Ricin is a plant glycoprotein extracted from castor beans. It is a deadly and highly toxic biological toxin. Ricin consists of two polypeptide chains, A and B, connected by a disulfide bond. The toxin B chain contains two galactose or galactose residue binding sites, which can bind to receptors containing galactose residues on the cell surface, enter the cytoplasm through invagination, and exert toxic effects. Although the research on ricin vaccines Rivax® and RVEcTM is progressing well, and monoclonal antibodies have shown significant effects in neutralizing ricin, so far, no vaccine or monoclonal antibody has been clinically approved and used. At present, the treatment of ricin poisoning can only rely on symptomatic treatment in clinical practice, and severe cases even need to be excreted from the body through plasma exchange. In addition, the production process of vaccines and antibody drugs is relatively cumbersome, costly, and has certain requirements for storage methods, which to a certain extent also limits the promotion and application of large-molecule ricin drugs.

[0003] Small molecule inhibitor drugs can exert their efficacy both inside and outside cells because of their good cell membrane permeability. In terms of treatment after ricin poisoning, small molecule ricin inhibitors have relatively broad application prospects. However, although the structural analysis of ricin has been relatively clear and there are many clear studies on its druggable targets, the small molecule inhibitors currently developed for the functional domain of ricin have not yet achieved anti-toxic activity comparable to that of monoclonal neutralizing antibodies. In addition, the poor solubility of some small molecule compounds and their large toxic side effects also limit their further research as therapeutic drugs. Although the efficacy of the small molecule inhibitors currently developed is limited, small molecule drugs are easier to develop as drugs than large molecule vaccines and antibodies. In addition, with the advancement and maturity of technologies such as artificial intelligence-assisted drug design and efficacy evaluation, scientific and technological empowerment has greatly improved the efficiency of small molecule drug research and development, and the development of more efficient ricin small molecule inhibitors has once again become a hot research direction against ricin.

[0004] At present, although there are some research directions for ricin poisoning, there is still a lack of effective therapeutic drugs. Existing treatment methods mainly focus on symptomatic supportive treatment, such as maintaining water and electrolyte balance, anti-shock treatment, etc. However, these methods have limited effects on reducing the core toxicity of ricin. Therefore, the development of a drug that can effectively counteract 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 technical problems existing in the art, the purpose of the present invention is to provide a medical use of the compound Pladienolide B as an anti-ricin toxin protective agent. The present invention creatively discovered for the first time and confirmed through experiments that the 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 has good clinical application prospects.

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

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

[0008] Formula (I).

[0009] Furthermore, the Pladienolide B has an anti-ricin toxicity effect.

[0010] Furthermore, the medicine also contains pharmaceutically acceptable adjuvants and / or excipients.

[0011] Furthermore, the pharmaceutically acceptable auxiliary materials and / or excipients are diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers and / or disintegrants.

[0012] Furthermore, 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 drops.

[0013] In the present invention, the Pladienolide B is a major analog of the macrolide family isolated from Streptomyces, and its Chinese name is pladienolide B. Pladienolide B is a highly effective inhibitor of hypoxia signaling and cancer cell proliferation. Currently, there is no research or report on the anti-toxic effect of Pladienolide B on ricin. Its corresponding CAS number is 445493-23-2, and its molecular formula is C 30 H 48 O8, molecular weight 536.70, structural formula is shown in the above formula (I). The present invention has no particular limitation on the specific source of the Pladienolide B, and those skilled in the art can purchase it through conventional channels.

[0014] In some embodiments, the pharmaceutically acceptable salt refers to a pharmaceutically acceptable salt of Pladienolide B. Specifically, the pharmaceutically acceptable salt of Pladienolide B refers to a salt form suitable for pharmaceutical preparations and clinical applications obtained by salt modification of Pladienolide B. The salts used in the salt modification process include, but are not limited to, inorganic acid salts (e.g., hydrochlorides, sulfates, phosphates), organic acid salts (e.g., citrates, maleates, tartrates), which are suitable for contact with patients within the scope of reliable medical judgment and will not produce inappropriate toxicity, irritation, allergic reactions, etc.

[0015] In some embodiments, examples of pharmaceutically acceptable salts of Pladienolide B include, but are not limited to, those having (as counter ions) alkali metal ions such as Na + , Li + or K + or salts with alkaline earth metal ions such as Ca 2+ or Mg 2+ or any other pharmaceutically acceptable metal ion such as Zn 2+ or Al 3+ or a pharmaceutically acceptable salt formed with an organic base such as diethanolamine, ethanolamine, N-methylglucamine, triethanolamine or tromethamine.

[0016] 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-methylglucamine or procaine.

[0017] In some embodiments, base addition salts of acidic compounds can be prepared by contacting the free acid form with a sufficient amount of the desired base in a conventional manner to form the salt. The free acid can be regenerated by contacting the salt form with an acid in a conventional manner and isolating the free acid.

[0018] In some embodiments, pharmaceutically acceptable salts may include alkali and alkaline earth metal based cations, such as sodium, potassium, calcium, lithium, magnesium, etc., and non-toxic ammonium, quaternary ammonium and amine cations, including but not limited to ammonium, tetramethylammonium, methylamine, dimethylamine, tetraethylammonium, trimethylamine, triethylamine, ethylamine, etc. Also contemplated are salts of amino acids, such as gluconate, arginate, galacturonate, etc.

[0019] In some embodiments, the hydrate refers to a compound obtained by combining the compound (Pladienolide B) of the present invention with water. Generally, the ratio of the number of water molecules contained in the hydrate of the compound to the number of molecules of the compound in the hydrate is determined. Therefore, the hydrate of the compound can be represented by the general formula R·xH2O, for example, wherein R is the compound (Pladienolide B) and x is a number greater than 0.

[0020] In some embodiments, the solvate refers to a solvent addition form of a compound containing a stoichiometric or non-stoichiometric solvent, including any solvated form of the compound (Pladienolide B) described herein. Conventional solvents include, but are not limited to, water, ethanol, acetic acid, methanol, DMSO, THF, ether, and the like. 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.

[0021] 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 three-dimensional space according to specific rules 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 lead to differences in the arrangement of molecules, resulting in different lattice structures. For example, in some solvents, molecules may be arranged in a tightly packed manner to form a compact lattice; under other conditions, there may be large gaps between molecules to form a loose lattice.

[0022] In some embodiments, the derivative refers to a Pladienolide B derivative. Any modified Pladienolide B obtained after modification of Pladienolide B falls within the protection scope of the present invention. Exemplarily, the Pladienolide B derivative includes but is not limited to: nanoparticle-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.

[0023] In some embodiments, the anti-ricin drug refers to a drug for treating, preventing, alleviating and / or improving diseases or symptoms associated with ricin poisoning.

[0024] A second aspect of the present invention provides a pharmaceutical composition.

[0025] Furthermore, the pharmaceutical composition comprises an effective amount of Pladienolide B or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof as described in the first aspect of the present invention.

[0026] In some embodiments, the pharmaceutical composition further comprises pharmaceutically acceptable adjuvants and / or excipients.

[0027] In the present invention, the pharmaceutically acceptable adjuvants and / or excipients are described in detail in Remington's Pharmaceutical Sciences (19th ed, 1995). These substances are used to help the stability of the drug or to help improve the activity of the active ingredient (i.e., Pladienolide B or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof as described above in the present invention), and the substances include but are not limited to: diluents, surfactants, wetting agents, adhesives, fillers, disintegrants, adsorption carriers, lubricants, stabilizers, bactericides, buffers, isotonic agents, chelating agents, pH control agents. The pharmaceutical composition thus prepared can be administered by any appropriate administration method known to those skilled in the art as needed.

[0028] In some embodiments, the pharmaceutically acceptable adjuvants and / or excipients may additionally contain liquids such as water, saline, glycerol, and ethanol.

[0029] In some embodiments, the pharmaceutical composition may further include other anti-ricin drugs. In the present invention, there is no particular limitation on the other anti-ricin drugs, and those skilled in the art may make conventional selections according to actual needs. For example, 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, Chinese herbal extracts against ricin, etc.

[0030] A third aspect of the present invention provides a pharmaceutical preparation.

[0031] Furthermore, the pharmaceutical preparation comprises the pharmaceutical composition described in the second aspect of the present invention.

[0032] Furthermore, the dosage form of the pharmaceutical preparation is a dosage form for enteral administration or a dosage form for parenteral administration.

[0033] Furthermore, the dosage form for administration through the gastrointestinal tract is a solution, granules, tablets, capsules, suspensions, powders, sustained-release preparations, effervescent preparations, emulsions, syrups or drops;

[0034] The non-intestinal administration dosage form is an injection dosage form, a respiratory tract administration dosage form, a cavity administration dosage form, a mucosal administration dosage form or a skin administration dosage form.

[0035] 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, oral preparations include tablets, capsules, and granules; injection preparations include solution injections and suspension injections; inhalation preparations include aerosols and powder sprays.

[0036] In some embodiments, when the pharmaceutical preparation is an oral preparation, it comprises Pladienolide B or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof, and pharmaceutically acceptable excipients, the excipients including but not limited to: fillers, disintegrants, lubricants, binders, wherein the fillers are selected from one or more of starch, lactose, and microcrystalline cellulose; the disintegrants are selected from one or more of cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, and cross-linked polyvinyl pyrrolidone; the lubricants are selected from one or more of magnesium stearate, talc, and micropowdered silica gel; the binders are selected from one or more of hydroxypropyl methylcellulose, povidone, and starch slurry.

[0037] In some embodiments, when the pharmaceutical preparation is an injection preparation, the solvent is one or more of water for injection, physiological saline, and 5% glucose injection, and excipients such as pH adjusters, osmotic pressure adjusters, and antioxidants can be added as needed. Among them, the pH adjuster is selected from one or more of hydrochloric acid, sodium hydroxide, and citric acid-sodium citrate buffer; the osmotic pressure adjuster is selected from one or more of sodium chloride, glucose, and mannitol; the antioxidant is selected from one or more of sodium sulfite, sodium pyrosulfite, and sodium thiosulfate.

[0038] In some embodiments, when the pharmaceutical preparation is an inhalation preparation, it comprises Pladienolide B or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof, and suitable excipients such as propellants, cosolvents, stabilizers, etc. 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.

[0039] In some embodiments, suitable administration methods for the pharmaceutical compositions or pharmaceutical preparations described in the present invention include any of the various methods and delivery systems known to those skilled in the art to physically introduce the pharmaceutical compositions or pharmaceutical preparations described in the present invention into the subject, and the administration methods include but are not limited to: oral administration, topical administration, parenteral administration, administration by inhalation spray, rectal administration, nasal administration, buccal administration, or administration by implanted drug storage devices, etc.

[0040] In some embodiments, when the pharmaceutical composition or pharmaceutical preparation provided by the present invention is actually used, its administration regimen and dosage regimen can be selected according to a variety of factors, including the type, species, age, weight, sex and type of disease to be treated of the subject; the severity of the disease to be treated; the route of administration; the patient's renal and liver function; and the specific compound used or other forms of the compound. A dosing and / or dosage regimen can be used, for example, to prevent a disease, inhibit (completely or partially inhibit) a disease, or stop the development of the disease. In a specific embodiment of the present invention, the disease refers to a disease associated with ricin poisoning.

[0041] Those skilled in the art will appreciate that, although the pharmaceutical composition or pharmaceutical preparation mentioned above in the present invention may further comprise pharmaceutically acceptable adjuvants and / or excipients, 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 may also be administered in their own form, i.e., the present invention may be achieved without adding any of the above-mentioned pharmaceutically acceptable adjuvants and / or excipients.

[0042] A fourth aspect of the present invention provides an in vitro method for inducing cell resistance to ricin for non-therapeutic purposes.

[0043] Furthermore, the method comprises: treating a system in need thereof with Pladienolide B or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof as described in the first aspect of the present invention.

[0044] In some embodiments, the present invention has no particular limitation on the system in need thereof. Exemplarily, the system includes a cell system, a subcellular system, a tissue system or an organ system in need thereof.

[0045] In addition, the present invention also provides a method for treating, preventing, alleviating and / or improving diseases or symptoms related to ricin poisoning, the method comprising: administering an effective amount of Pladienolide B as described above or its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof, pharmaceutical compositions or pharmaceutical preparations to a subject in need.

[0046] In some embodiments, the diseases or symptoms associated with ricin poisoning include the following aspects: (1) Digestive system: Ricin can irritate the gastrointestinal mucosa, causing severe nausea and vomiting. Excessive vomiting can lead to dehydration and electrolyte imbalance. At the same time, the patient will feel severe abdominal pain and diarrhea. In severe cases, it can cause damage to the intestinal mucosa, bleeding, and enteritis. (2) Cardiovascular system: The toxin can damage vascular endothelial cells, increase vascular permeability, and cause the liquid components in the blood to seep into the interstitial space, causing edema. For example, pulmonary edema can cause difficulty breathing; blood vessel damage can also cause hypotension, which can develop into shock in severe cases and endanger life. In addition, heart function may also be affected, resulting in arrhythmia, heart failure and other diseases. (3) Nervous system: The poisoned person will experience headaches and dizziness. In severe cases, it can cause convulsions, abnormal discharge of brain neurons, and then coma. (4) Urinary system: The kidneys, as important excretory organs, can also be attacked by ricin. The toxin can damage the filtering and excretion functions of the kidneys, leading to renal insufficiency, hematuria, proteinuria, and inability to excrete metabolic wastes normally. (5) Respiratory system: If ricin poisoning is caused by inhalation, it will directly irritate the respiratory tract, causing coughing and chest pain. Airway inflammation and edema can lead to difficulty breathing, and in severe cases, it can develop into respiratory failure, making it impossible for the body to obtain sufficient oxygen supply.

[0047] In the present invention, the effective amount refers to an amount having a preventive or therapeutic effect or an amount required to produce a preventive or therapeutic effect in a subject. For example, a pharmaceutically effective amount for prevention or treatment refers to the amount of a drug required to produce the desired preventive or therapeutic effect, and the preventive 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 subject (such as height, weight, sex, age and medication history), the type of disease, and the severity of the disease.

[0048] In the present invention, the treatment and / or prevention refers to the medical management of patients for the purpose of preventing, curing, improving or stabilizing a disease, pathological state or condition. The term includes active therapy, i.e., treatment specifically for the purpose of improving a disease, pathological state or condition, and also includes etiological treatment, i.e., treatment for the purpose of removing the cause of the relevant disease, pathological state or condition. In addition, the treatment and / or prevention also includes palliative treatment, i.e., treatment designed to relieve symptoms rather than cure a disease, pathological state or condition; the term also includes preventive treatment, i.e., treatment for the purpose of minimizing or partially or completely inhibiting the development of the relevant disease, pathological state or condition; and supportive treatment, i.e., treatment used to supplement another specific therapy for the purpose of improving the relevant disease, pathological state or condition.

[0049] In the present invention, the subject includes, but is 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 older 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.

[0050] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0051] The present invention discloses for the first time the novel application of Pladienolide B in anti-ricin toxin, and confirms through experiments 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 anti-ricin toxin related drugs, and has good clinical application prospects and important transformation significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 The effect of different doses of Pladienolide B on the sensitivity of cells to ricin;

[0053] Figure 2Figure 3 shows the effect of Pladienolide B treatment on ricin sensitivity of cells at different time periods, where A shows the cell survival curves of cells treated with DMSO / Pladienolide B for 48 h after different concentrations of ricin treatment; B shows the cell survival curves of cells treated with DMSO / Pladienolide B for 6 h and different concentrations of ricin treatment for 48 h; C shows the cell survival curves of cells treated with DMSO / Pladienolide B for 12 h and different concentrations of ricin treatment for 48 h; D shows the cell survival curves of cells treated with DMSO / Pladienolide B for 24 h and different concentrations of ricin treatment for 48 h. DETAILED DESCRIPTION

[0054] The present invention is further described below in conjunction with specific embodiments. The following specific embodiments are only used to explain the present invention and cannot be construed as limiting the present invention. It can be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and purposes of the present invention, and 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 available to those of ordinary skill in the art. If not otherwise specified, they can all be obtained from commercial sources. The experimental methods for which specific conditions are not specified in the present invention are usually implemented according to conventional conditions or according to the conditions recommended by the manufacturer. In particular, the following examples 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 examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0055] Example 1 Pladienolide B induces cell resistance to ricin in a dose-dependent manner

[0056] 1. Experimental methods

[0057] CCK-8 assay for cell viability: Hela cells were pretreated with different doses of Pladienolide B for 24 h. The cells were subcultured to 96-well plates and ricin was added at 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, and 0 ng·mL after the cells adhered to the wall. -1Serum-free DMEM medium was used, and three replicate wells (n=3) were set for each concentration. After 48 h of ricin treatment, 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 ELISA reader at a wavelength of 450 nm. The cell survival rate of each concentration experimental well was calculated according to the formula: cell survival rate = [1-(experimental well-control well) / (control well-blank well)]×100%, and the survival curve was fitted and drawn.

[0058] 2. Experimental results

[0059] In this example, the antitoxic 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. Figure 1 The results shown in the figure show that 1 nM Pladienolide B pretreatment can make cells have a more obvious ricin tolerance effect. With the increase of Pladienolide B treatment concentration, the ability of cells to resist ricin, especially to tolerate high concentrations of ricin, gradually increases, indicating that Pladienolide B induces cells to resist ricin in a dose-dependent manner. Among them, when the 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 show that Pladienolide B can effectively induce cells to resist ricin in a dose-dependent manner.

[0060] Example 2 Pladienolide B induces cell resistance to ricin in a time-dependent manner

[0061] 1. Experimental methods

[0062] This example further explored whether different pretreatment times of Pladienolide B affect the cell anti-toxic phenotype induced by it. The pretreatment time of cells with 100 nM Pladienolide B was set to 0, 6, 12, and 24 h, and the specific cell viability detection method was as described in the experimental method of Example 1 above.

[0063] 2. Experimental results

[0064] Figure 2 A shows the sensitivity of normal cells to different concentrations of ricin (cells were not treated with Pladienolide B). When the pretreatment time of Pladienolide B was 6 h, the cell survival curve began to shift to the right, and its IC 50From 0.19 ng / mL to 0.40 ng / mL, there is a 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 about 50% of the cells still survived under the condition of high concentration (100 ng / mL) of ricin ( Figure 2 C); Consistent with previous results, when Pladienolide B was pretreated for up to 24 h, ricin had almost no killing effect on cells ( Figure 2 D). The above results suggest that the anti-toxic effect of Pladienolide B on cells is time-dependent.

[0065] The experimental results of the above examples show that Pladienolide B has an effective effect of 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 its pharmaceutically acceptable salts, hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof in the preparation of anti-ricin drugs, wherein the structural formula of Pladienolide B is shown in formula (I): Formula (I).

2. The use according to claim 1, characterized in that: The Pladienolide B has an anti-ricin toxicity effect.

3. The use according to claim 1, characterized in that: The medicament further comprises pharmaceutically acceptable adjuvants and / or excipients.

4. The use according to claim 3, characterized in that: The pharmaceutically acceptable auxiliary materials and / or excipients are diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers and / or disintegrants.

5. The use according to claim 1, characterized in that: The dosage form of the drug is solution, sustained-release agent, suspension, granule, tablet, capsule, powder, emulsion, syrup or drops.

6. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises an effective amount of the Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof as claimed in claim 1.

7. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the pharmaceutical composition according to claim 6.

8. The pharmaceutical preparation according to claim 7, characterized in that The dosage form of the pharmaceutical preparation is a dosage form for enteral administration or a dosage form for parenteral administration.

9. The pharmaceutical preparation according to claim 8, characterized in that The dosage form for administration through the gastrointestinal tract is solution, granules, tablets, capsules, suspensions, powders, sustained-release preparations, effervescent preparations, emulsions, syrups or drops; The non-intestinal administration dosage form is an injection dosage form, a respiratory tract administration dosage form, a cavity administration dosage form, a mucosal administration dosage form or a skin administration dosage form.

10. A method for inducing cells to resist ricin in vitro for non-therapeutic purposes, characterized in that: The method comprises: treating a system in need thereof with the Pladienolide B or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate, crystalline form or derivative thereof as described in claim 1.

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