New application of compound Pladienolide B in resisting abrus precatorius toxin

Abstract

The invention discloses a new application of a compound Pladienolide B. The invention creatively discovers that the Pladienolide B has an effect of resisting the toxicity of the abrus precatorius toxin for the first time and can be used in the development of an abrus precatorius toxin resisting medicine, a theoretical basis is provided for the research and development of the abrus precatorius toxin resisting medicine, the new application of the Pladienolide B is developed, and the application of the Pladienolide B in resisting the abrus precatorius toxin is developed. The invention provides a brand new method for treating or preventing diseases or symptoms related to abrus precatorius toxin poisoning, and has a wide application prospect in the technical field of treatment of diseases or symptoms related to abrus precatorius toxin poisoning.

Description

Technical Field

[0001] The invention belongs to the field of biomedical technology, and in particular relates to a new use of a compound Pladienolide B in resisting abrin toxin. Background Art

[0002] Abrin is a toxic protein found in the seeds of the leguminous plant Abrus precatorius. Its toxicity is far greater than that of ricin, and even a trace amount can cause severe cell damage or even death. The toxin inhibits protein synthesis in cells, destroys cell function, and then causes multiple organ failure. Once substances containing abrin are accidentally ingested, gastrointestinal reactions such as nausea, vomiting, and diarrhea may occur in the early stages. As the toxin spreads in the body, it will quickly erode important organs of the human body, causing irreversible damage to the liver, kidneys, heart, etc., and even cause death in severe cases. Moreover, abrin toxin is stable in nature, and it is difficult to completely inactivate it with conventional treatment methods, which undoubtedly further increases the difficulty of prevention and control. Due to the high toxicity of abrin toxin and the potential threat of bioterrorism, the research on abrin toxin is not only related to the medical field, but also to public safety.

[0003] However, there is still no specific antidote for abrin toxin, which makes the development of new drugs against abrin toxin an urgent and important task. In view of the great harm of abrin toxin, the development of new drugs against abrin toxin is imminent. At present, there are no specific therapeutic drugs and mature treatment plans for abrin toxin poisoning. Most of the existing treatments can only relieve symptoms, but cannot fundamentally eliminate toxins and save patients' lives. The development of new drugs against abrin toxin can not only fill the gap in this direction in the medical field, provide effective treatment for patients with abrin toxin poisoning, and significantly improve the survival rate of patients, but also have great significance for maintaining public health security. Pladienolide B is the main analogue of the macrolide family isolated from Streptomyces. In the field of anti-abrin toxin, there is still a gap in the research of Pladienolide B. Summary of the invention

[0004] The purpose of the present invention is to provide a new use of the compound Pladienolide B in anti-abrindus toxin, to provide a safe and effective drug for the treatment of diseases or symptoms related to abrindus toxin poisoning, so as to overcome the technical problem that there is an urgent need for effective anti-abrindus toxin drugs in the current field.

[0005] The above-mentioned object of the present invention is achieved through the following technical solutions:

[0006] In a first aspect, the present invention provides a use of Pladienolide B or a pharmaceutically acceptable salt thereof in the preparation of an anti-abrinia toxin drug, wherein the structural formula of the Pladienolide B is shown in formula (I):

[0007] Formula (I).

[0008] Furthermore, the Pladienolide B has an anti-abrinia toxin toxicity effect.

[0009] Furthermore, the medicine also contains pharmaceutically acceptable adjuvants and / or excipients.

[0010] Furthermore, the dosage form of the drug is an oral dosage form, a parenteral dosage form or a topical dosage form.

[0011] Furthermore, the dosage form of the drug is solution, powder injection, tablet, capsule, granule, powder, pill, powder aerosol or suspension.

[0012] Furthermore, the administration dosage of Pladienolide B or its pharmaceutically acceptable salt is 10 nM-100 mM.

[0013] Furthermore, the administration dosage of Pladienolide B or its pharmaceutically acceptable salt is 50 nM-100 nM.

[0014] In the present invention, the Pladienolide B is a major analogue of the macrolide family isolated from Streptomyces, and its corresponding Chinese name is pladienolide B. Pladienolide B is a highly effective inhibitor of hypoxia signals and cancer cell proliferation. Currently, there is no research or report on the anti-toxic effect of Pladienolide B on abrin toxin. 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.

[0015] In some embodiments, the hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof corresponding to the Pladienolide B are also within the protection scope of the present invention, that is, the use of the hydrates, enantiomers, diastereomers, solvates, crystalline forms or derivatives thereof corresponding to Pladienolide B in the preparation of anti-abrinia toxin drugs also falls within the protection scope of the present invention.

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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.

[0020] 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.

[0021] In a specific embodiment of the present invention, the present invention proves through cell experiments that Pladienolide B has an anti-abrin toxin toxicity effect, that is, proves the effectiveness of Pladienolide B against abrin toxin, and Pladienolide B or its pharmaceutically acceptable salt can be effectively used in the preparation of anti-abrin toxin drugs.

[0022] In some embodiments, the anti-abrin toxin includes treating, preventing, alleviating and / or improving diseases or symptoms related to abrin poisoning. Among them, treatment refers to the treatment of patients diagnosed with abrin poisoning, prevention refers to prevention for high-risk groups who may be exposed to abrin poisoning environment, and alleviating or improving refers to the alleviating or improving of diseases or symptoms related to abrin poisoning in patients with abrin poisoning.

[0023] In some embodiments, the pharmaceutically acceptable adjuvants and / or excipients include, but are not limited to, stabilizers, preservatives, solubilizers, wetting agents, emulsifiers, buffers, sweeteners, colorants, salts for regulating osmotic pressure, flavoring agents, masking agents, or antioxidants. In addition, by adding a component that can delay the absorption of the active ingredient (i.e., Pladienolide B or its pharmaceutically acceptable salt as described above) to the drug, the absorption of the active ingredient in the drug can be prolonged.

[0024] In a second aspect, the present invention provides a pharmaceutical composition against abrinida toxin, the pharmaceutical composition comprising Pladienolide B or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention.

[0025] In some embodiments, the pharmaceutical composition comprises a therapeutically and / or preventively effective amount of Pladienolide B or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention. In other embodiments, the main active ingredient of the pharmaceutical composition is Pladienolide B or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention, and in addition to the Pladienolide B or a pharmaceutically acceptable salt thereof, the pharmaceutical composition may further comprise other drugs that can be used for the treatment and / or prevention, or for the auxiliary treatment and / or prevention of diseases or symptoms associated with abrin poisoning.

[0026] In some embodiments, the other drugs that can be used to treat and / or prevent, or to assist in the treatment and / or prevention of diseases or symptoms related to abrin poisoning include but are not limited to: adsorbents (e.g., medicinal charcoal, etc.), antiemetics (e.g., metoclopramide, ondansetron, etc.), antidiarrheals (e.g., montmorillonite powder, etc.), liver-protecting drugs (e.g., polyene phosphatidylcholine, reduced glutathione, etc.), kidney-protecting drugs (e.g., Shenkang injection, Bailing capsules, etc.), drugs for regulating electrolytes and acid-base balance (e.g., potassium chloride, sodium chloride, sodium bicarbonate, etc.), and blood products (e.g., plasma, red blood cell suspension, etc.).

[0027] In the present invention, the other drugs that can be used to treat and / or prevent, or to assist in the treatment and / or prevention of diseases or symptoms related to abrin poisoning are not limited to the specific drugs listed above in the present invention, and any drugs that may be used to treat and / or prevent, or to assist in the treatment and / or prevention of diseases or symptoms related to abrin poisoning shall fall within the scope of protection of the present invention.

[0028] It should be noted that, in the case where the present invention has clearly proved through detailed cell experiments that Pladienolide B has an anti-abrin toxin toxicity effect, those skilled in the art, combined with common knowledge, can know that the present invention can be achieved by using the aforementioned Pladienolide B or its pharmaceutically acceptable salt alone. Therefore, the use of the aforementioned Pladienolide B or its pharmaceutically acceptable salt alone or in combination with other drugs will fall within the protection scope of the present invention.

[0029] In a third aspect, the present invention provides a pharmaceutical preparation against abrinus toxin, wherein the pharmaceutical preparation comprises the pharmaceutical composition described in the second aspect of the present invention.

[0030] Furthermore, the dosage form of the pharmaceutical preparation includes, but is not limited to, oral dosage form, parenteral dosage form, and topical dosage form.

[0031] In some embodiments, the oral dosage form refers to a dosage form in which the drug is absorbed into the gastrointestinal tract after oral administration to exert its efficacy. The oral dosage form includes but is not limited to: tablets, capsules, granules, powders, pills, syrups, oral solutions, oral suspensions, and emulsions.

[0032] Specifically, the tablet is a sheet preparation obtained by mixing the drug with the auxiliary materials and then compressing them. It has the advantages of accurate dosage, good stability, high production efficiency, and convenient administration. It can be divided into various types such as ordinary tablets, coated tablets, chewable tablets, and dispersible tablets.

[0033] Specifically, the capsule is divided into hard capsule and soft capsule. Hard capsule is made by filling drug powder or granules into hollow hard capsule; soft capsule is made by dissolving or suspending the drug in a suitable oily or non-oily liquid medium and then using a compression method or a dripping method. Capsules can cover up the bad smell of drugs, improve drug stability, and are easy to take.

[0034] Specifically, the granules are dry granular preparations with a certain particle size made by mixing drugs with suitable excipients. They can be divided into soluble granules, suspension granules, effervescent granules, etc. Granules are easy to dissolve, absorb quickly, and are easy to carry and take.

[0035] Specifically, the powder is a dry powder preparation prepared by crushing and uniformly mixing the drug and suitable auxiliary materials. The powder has a small particle size, a large specific surface area, is easy to disperse, and has a fast onset of action, but has relatively poor stability.

[0036] Specifically, the pills are spherical or quasi-spherical preparations made from fine powder or extracts of the drug and suitable adhesives or other excipients. Depending on the excipients used and the preparation method, they can be divided into honey pills, water pills, water-honey pills, paste pills, wax pills, etc.

[0037] Specifically, the syrup refers to a concentrated sucrose aqueous solution containing a drug. The sucrose in the syrup can mask the bitter taste of the drug and has a certain antiseptic effect. It has a good taste and is particularly suitable for children.

[0038] Specifically, the oral solution is a clear liquid preparation for oral administration prepared by dissolving the drug in a suitable solvent. The drug is evenly dispersed in the solution, is quickly absorbed, and has high bioavailability.

[0039] Specifically, the oral suspension is a non-uniform liquid preparation formed by dispersing a poorly soluble solid drug in a dispersion medium in a microparticle state. In order to ensure the stability and uniformity of the drug, auxiliary materials such as suspending agents and wetting agents are often added.

[0040] Specifically, the emulsion is a heterogeneous liquid preparation formed by emulsifying two immiscible liquids, one of which is dispersed in the other liquid in the form of droplets. Oral emulsions can improve the taste and stability of drugs and increase the bioavailability of drugs.

[0041] In some embodiments, the parenteral dosage form refers to a dosage form that delivers the drug into the body by other routes other than oral administration. The parenteral dosage form includes, but is not limited to, injections, aerosols, sprays, powder sprays, suppositories, patches, and implants.

[0042] Specifically, the injection is the most common parenteral dosage form, including solution injection, suspension injection, emulsion injection and sterile powder for injection, etc. It can be administered by intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, etc. Intravenous injection can make the drug quickly enter the blood circulation and exert a rapid effect, which is suitable for emergency treatment and drugs that need to take effect quickly; the absorption rate of intramuscular injection and subcutaneous injection is relatively slow, but the drug effect lasts longer.

[0043] Specifically, the aerosol is a preparation made by encapsulating the drug and a suitable propellant in a pressure-resistant container with a special valve system. When used, the drug is sprayed out in a mist with the help of the pressure of the propellant, and inhaled through the respiratory tract or directly sprayed to the cavity mucosa, skin and other parts to take effect. The aerosol has a rapid and localized effect, the drug is evenly distributed, the irritation of local administration can be reduced, and it is easy to use.

[0044] Specifically, the spray refers to a drug-containing solution, emulsion or suspension filled in a special device, which releases the contents in the form of mist by means of pressure from a manual pump, high-pressure gas, ultrasonic vibration or other methods. It can be used for pulmonary inhalation, nasal mucosal administration or skin administration, etc.

[0045] Specifically, the powder inhalation is inhalation powder inhalation, non-inhalation powder inhalation and external powder inhalation. Inhalation powder inhalation is a preparation in which the patient actively inhales the atomized drug into the lungs; non-inhalation powder inhalation is a preparation in which the drug powder is sprayed onto the cavity mucosa using a special dry powder delivery device; external powder inhalation is a preparation in which the drug powder is sprayed onto the skin or mucosal surface through a special device. Powder inhalation has the advantages of no propellant, good drug stability, and accurate dosage.

[0046] Specifically, the suppository is a solid preparation with a certain shape made of a drug and a suitable matrix for administration to the human body cavity. Commonly used are rectal suppositories. After the suppository melts or dissolves in the cavity, the drug can be absorbed through the mucosa into the blood circulation, avoiding the first-pass effect of the liver, and is suitable for patients who are not suitable for oral administration.

[0047] Specifically, the patch includes transdermal patch and mucosal patch. Transdermal patch is a patch made by evenly dispersing or dissolving the drug in a sticky matrix and coating it on a backing material, which slowly releases the drug into the blood circulation through the skin to achieve systemic therapeutic effects; mucosal patch is a preparation that is attached to the surface of mucous membranes such as the oral cavity, nasal cavity, and conjunctiva of the eye, and the drug is absorbed through the mucosa to exert local or systemic effects.

[0048] Specifically, the implant is a sterile solid preparation made of drugs and excipients for implantation in the body. Generally, a special syringe is used to implant the implant into the subcutaneous tissue or muscle tissue of the human body. The drug is slowly released, and the effective blood drug concentration can be maintained for a long time, playing a long-term therapeutic role.

[0049] In some embodiments, the topical dosage form refers to a dosage form that allows the drug to act on local tissues to achieve a local therapeutic effect. The topical dosage form includes, but is not limited to: topical solutions, lotions, liniments, ointments, and gels.

[0050] Specifically, the external solution is a clear liquid preparation for external use prepared by dissolving a drug in a suitable solvent.

[0051] Specifically, the lotion is a drug-containing solution, emulsion or suspension, which is a preparation for cleaning or applying to undamaged skin.

[0052] Specifically, the liniment refers to a liquid preparation made of ethanol, oil or a suitable solvent for rubbing on undamaged skin.

[0053] Specifically, the ointment is a uniform semisolid external preparation prepared by mixing a drug with an oily or water-soluble base.

[0054] Specifically, the gel is a uniform, suspension or emulsion-type thick liquid or semisolid preparation made of a drug and an auxiliary material capable of forming a gel. Topical gels are usually applied to the skin or mucous membranes.

[0055] In a fourth aspect, the present invention provides an in vitro method for inducing cells to resist abrin toxin for non-therapeutic purposes, the method comprising: treating a system in need thereof with Pladienolide B or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention.

[0056] 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.

[0057] In some embodiments, the cell system, subcellular system, tissue system or organ system in need is a system in which resistance to abrin toxin is induced.

[0058] In some embodiments, the specific dosage of the Pladienolide B or its pharmaceutically acceptable salt can be routinely selected and adjusted by those skilled in the art according to actual conditions.

[0059] In a fifth aspect, the present invention provides a method for treating, preventing, alleviating and / or improving diseases or symptoms related to abrin poisoning, the method comprising: administering to a subject in need thereof an effective amount of Pladienolide B or a pharmaceutically acceptable salt thereof described in the first aspect of the present invention, the pharmaceutical composition described in the second aspect of the present invention, and / or the pharmaceutical preparation described in the third aspect of the present invention.

[0060] In some embodiments, the diseases or symptoms associated with abrin poisoning include, but are not limited to, digestive system symptoms, liver damage, kidney damage, cardiovascular system symptoms, and nervous system symptoms caused by abrin poisoning.

[0061] In some embodiments, the digestive system symptoms caused by abrin poisoning include but are not limited to: severe vomiting, diarrhea, abdominal pain, gastrointestinal bleeding; the liver damage caused by abrin poisoning includes but is not limited to: jaundice, abnormal liver function; the kidney damage caused by abrin poisoning includes but is not limited to: oliguria or anuria, edema, uremia; the cardiovascular system symptoms caused by abrin poisoning include but are not limited to: arrhythmia, hypotension; the nervous system symptoms caused by abrin poisoning include but are not limited to: headache, dizziness, fatigue, drowsiness, convulsions.

[0062] In some embodiments, the subject comprises one or more animals, including, for example, cattle, horses, sheep, primates, avian and rodent species. The subject can be a mammal, a bird, a fish, a reptile or an amphibian. The mammal includes a human or a non-human mammal. In other embodiments, the subject can be a mouse, a rat, a hamster, a ferret, a gerbil, a rabbit, a monkey, a chimpanzee, a horse, a donkey, a sheep, a pig, a chicken, a goat, a cat or a dog. In a preferred embodiment of the present invention, the subject is a human.

[0063] In some embodiments, the Pladienolide B or its pharmaceutically acceptable salt, pharmaceutical composition or pharmaceutical preparation as described above of the present invention may be administered to the subject by oral administration, injection administration or topical administration. For example, the method may include administering Pladienolide B or its pharmaceutically acceptable salt, pharmaceutical composition or pharmaceutical preparation as described above of the present invention to the subject three times a day, once a day, once every two days, etc. In other embodiments, injection administration may include subcutaneous injection, intramuscular injection, intravenous injection, etc. In other embodiments, injection administration may include directly injecting Pladienolide B or its pharmaceutically acceptable salt, pharmaceutical composition or pharmaceutical preparation as described above of the present invention into the subject. In other embodiments, a combination of different administration modes may also be used. The present invention does not particularly limit the specific administration mode, and those skilled in the art may make a conventional selection according to actual needs.

[0064] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0065] The present invention creatively discovers for the first time that the compound Pladienolide B has an anti-abrinia toxin toxic effect and can be used in the development of anti-abrinia toxin drugs. The present invention provides a theoretical basis for the research and development of anti-abrinia toxin drugs, opens up a new use of Pladienolide B, and provides a new method for treating or preventing diseases or symptoms related to abrinia toxin poisoning. It has broad application prospects in the technical field of treating diseases or symptoms related to abrinia toxin poisoning. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] Figure 1 The effect of different doses of Pladienolide B on the sensitivity of cells to Abrin toxin;

[0067] Figure 2 The figure shows the effect of Pladienolide B pretreatment for different time periods on the sensitivity of cells to abrin toxin, where A: pretreatment time 6 h; B: pretreatment time 12 h; C: pretreatment time 24 h. DETAILED DESCRIPTION

[0068] 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.

[0069] Example 1 Pladienolide B induces cell resistance to abrin toxin in a dose-dependent manner

[0070] 1. Experimental methods

[0071] In this example, Hela cells were pretreated with different concentrations of Pladienolide B (PB or Pladi B) for 24 h, and then treated with different concentrations of Abrin. The IC50 values ​​of the blank control DMSO group and the Pladienolide B pretreatment group were compared to determine the effect of Pladienolide B on the cytotoxic effect induced by Abrin. The specific experimental method is as follows:

[0072] CCK-8 method to detect cell viability: Hela cells were pretreated with 1, 6.25, 12.5, 25, and 50 nM of the compound Pladienolide B for 24 h. The cells were subcultured to 96-well plates, and after the cells adhered to the wall, Abrinus abrinus toxin was added at concentrations of 200, 100, 50, 25, 12.5, 6.25, 3.125, 1.5625, 0.78125, and 0 ng·mL -1 Serum-free DMEM medium was used, and three replicate wells (n=3) were set for each concentration. After 24 h of abrin toxin treatment, 10 μL 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 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.

[0073] 2. Experimental results

[0074] In this example, cells were pretreated with different doses of Pladienolide B for 24 h. After the cells pretreated with compound Pladienolide B were treated with different concentrations of abrin for 24 h, the cell viability levels of each group were detected. Figure 1 As shown, from Figure 1 The results shown show that 25 nM Pladienolide B pretreatment can make the cells have a more obvious tolerance effect to abrin toxin. With the increase of Pladienolide B treatment concentration, the cells' ability to resist abrin toxin, especially to tolerate high concentrations of abrin toxin, gradually increases, indicating that Pladienolide B induces cells to resist abrin toxin in a dose-dependent manner. Among them, when the cells were pretreated with 50 nM Pladienolide B, they showed a completely tolerant phenotype to 200 ng / mL of abrin toxin, while the cell survival rate of the control group was only 1%. The above results show that Pladienolide B can effectively resist the toxicity of abrin toxin and is dose-dependent, that is, this example proves that Pladienolide B has the effect of effectively inhibiting the toxicity of abrin toxin and can be used in the preparation of anti-abrin toxin drugs.

[0075] Example 2 Pladienolide B induces cell resistance to abrin toxin in a time-dependent manner

[0076] 1. Experimental methods

[0077] This example further explored whether different pretreatment times of Pladienolide B affect the cell anti-toxic phenotype induced by it. The pretreatment time of 25 nM Pladienolide B was set to 6, 12, and 24 h, and the specific experimental method was as follows:

[0078] CCK-8 assay for cell viability: Hela cells were pretreated with 25 nM of Pladienolide B for 6 h and 12 h. Cells were subcultured to 96-well plates and after cells adhered to the wall, Abrinus abrinosa toxin was added at concentrations of 200, 100, 50, 25, 12.5, 6.25, 3.125, 1.5625, 0.78125, 0.390625, 0.1953125, and 0 ng·mL -1 Hela cells were pretreated with 25 nM of Pladienolide B for 24 h, and then abrin toxin was added at concentrations of 200, 100, 50, 25, 12.5, 6.25, 3.125, 1.5625, and 0 ng·mL -1 Serum-free DMEM medium was used, and three replicate wells (n=3) were set for each concentration. After 24 h of abrin toxin treatment, 10 μL 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 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.

[0079] 2. Experimental results

[0080] In this example, 25 nM Pladienolide B was used to pretreat cells for 6, 12, and 24 h. When the Pladienolide B pretreatment time was up to 6 h, the sensitivity of the experimental group cells to abrin toxin did not change significantly compared with the DMSO control group cells ( Figure 2 A); When Pladienolide B was pretreated for 12 or 24 h, abrin had almost no killing effect on cells ( Figure 2 B, 2C). The above results indicate that the anti-abrin toxin effect induced by Pladienolide B in cells has a certain time dependence.

[0081] The experimental results of the above Examples 1 and 2 show that Pladienolide B has an effective inhibitory effect on abrin toxin, can effectively induce cells to resist the toxic effects of abrin toxin, and has a certain dose dependence and time dependence.

Claims

1. Use of Pladienolide B or its pharmaceutically acceptable salt in the preparation of an anti-abrinia toxin drug, characterized in that: The structural formula of the 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-abrinia toxin 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 1, characterized in that The dosage form of the drug is an oral dosage form, a parenteral dosage form or a topical dosage form.

5. The use according to claim 1, characterized in that: The dosage form of the drug is solution, powder injection, tablet, capsule, granule, powder, pill, powder spray or suspension.

6. The use according to claim 1, characterized in that: The administration dosage of Pladienolide B or its pharmaceutically acceptable salt is 10 nM-100 mM.

7. The use according to claim 6, characterized in that The administration dosage of Pladienolide B or its pharmaceutically acceptable salt is 50 nM-100 nM.

8. A pharmaceutical composition for resisting Abrus toxin, characterized in that: The pharmaceutical composition comprises the Pladienolide B or a pharmaceutically acceptable salt thereof as claimed in claim 1.

9. A pharmaceutical preparation for resisting Abrus toxin, characterized in that: The pharmaceutical preparation comprises the pharmaceutical composition according to claim 8.

10. A method for inducing cells to resist abrin toxin 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 thereof as described in claim 1.

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