Compositions comprising cabazitaxel and lipids for oral administration

Abstract

The invention relates to a cabazitaxel composition and application of the cabazitaxel composition. Embodiments provide a composition comprising cabazitaxel and at least one lipid and / or cougsterol, and / or a cougsterol derivative, and / or sodium cholesterol sulfate, in the form of a tablet or capsule, and administering the composition to a subject.

Description

Invention Field

[0001] This invention relates to compositions comprising cabazitaxel and lipids. The invention also relates to compositions comprising cabazitaxel, guggulsterol, and / or guggulsterol derivatives and / or sodium cholesterol sulfate. In some embodiments, the invention relates to compositions comprising cabazitaxel and lipids (including phosphatidylcholine and phosphatidylglycerol). In preferred embodiments, the invention relates to compositions comprising cabazitaxel, phosphatidylcholine, and guggulsterol or guggulsterol derivatives or sodium cholesterol sulfate. In some embodiments, the invention also relates to tablet or capsule compositions comprising cabazitaxel and excipients. The invention also relates to administering the compositions to mammalian subjects for the treatment or prevention of disease. The compositions of the invention are suitable for industrial-scale practice and can be carried out, for example, in a continuous process. Background of the Invention

[0002] Taxanes have become an important class of chemotherapy drugs, widely used as monotherapy and in combination with other drugs to treat various solid malignancies. Cabazitaxel is a novel second-generation semi-synthetic natural taxane derivative. Cabazitaxel's mechanism of action is similar to that of paclitaxel and docetaxel. It binds to the N-terminal amino acid of the P-tubule subunit, promoting microtubule polymerization and inhibiting microtubule cell division, thereby arresting the tumor cell cycle and tumor proliferation. Cabazitaxel is superior to paclitaxel and docetaxel because it has an additional methyl group, resulting in a lower affinity for P-glycoproteins. This makes it effective in treating docetaxel-resistant tumors.

[0003] Kabatasai with Jevtana ® It is marketed under the brand name and approved for the treatment of hormone-refractory metastatic prostate cancer patients who have previously received docetaxel-containing regimens. Individual doses of cabazitaxel are calculated based on body surface area (BSA) and are given at 25 mg / m². 2 Administer a one-hour intravenous infusion every three weeks, along with oral prednisone at a dose of 10 mg.

[0004] Jevtana ® This is a sterile, non-water-soluble concentrate for infusion. Each 1.5 ml of polysorbate 80 contains 60 mg of cabazitaxel, packaged in a glass vial, and includes a solvent for diluting the concentrate. This solvent is a 13% w / w sterile, pyrogen-free aqueous solution of ethanol. This concentrate and solvent are used to prepare a 10 mg / ml premixed cabazitaxel solution, which is then diluted in an infusion bag with 0.9% saline or 5% glucose solution.

[0005] Taxanes, including cabazitaxel, are highly lipophilic and practically insoluble in water. Due to their insolubility, various solubilizers, such as polysorbate 80, Cremophore EL, and ethanol, have been successfully formulated for intravenous administration of taxanes. However, the use of polysorbate 80, Cremophore EL, and ethanol can cause hypersensitivity reactions and infusion-related toxicities. To reduce the risk of these side effects, patients typically receive pre-treatment with corticosteroids before receiving taxane therapy.

[0006] Furthermore, all taxanes are inherently cytotoxic. The main dose-limiting toxicity of cabazitaxel is fatal febrile neutropenia; therefore, complete blood counts should be monitored weekly and before each treatment cycle, and G-CSF supplementation should be administered as needed. Other toxicities include nausea and vomiting.

[0007] To avoid the toxic effects of cabazitaxel and the excipients in currently commercially available intravenous products, it is necessary to develop novel cabazitaxel compositions for oral administration. Summary of the Invention

[0008] This invention provides compositions containing cabazitaxel. In some embodiments, the composition comprises phosphatidylcholine. In some embodiments, the composition further comprises one or more of gulosterol, gulosterol derivatives, and / or sodium cholesterol sulfate. In some preferred embodiments, the composition further comprises other excipients. Some embodiments involve administering a composition containing cabazitaxel to a subject. In some embodiments, the subject is a mammal. In a preferred embodiment, the subject is a human.

[0009] In some embodiments, the present invention provides a composition comprising cabazitaxel and phosphatidylcholine for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, the composition for oral delivery is in tablet or capsule form. In a preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0010] In some embodiments, the compositions of the present invention comprise cabazitaxel and phosphatidylglycerol for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, the compositions for oral delivery are in tablet or capsule form. In a preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0011] In some embodiments, this document provides compositions comprising cabazitaxel and gugursterol for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, the composition for oral delivery is in tablet or capsule form. In a preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0012] In some embodiments, the present invention provides compositions comprising cabazitaxel and gugursterol derivatives for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, oral delivery is in the form of tablets or capsules. In a more preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0013] In some embodiments, the present invention provides a composition comprising cabazitaxel and sodium cholesterol sulfate for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, oral delivery is in the form of tablets or capsules. In a more preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0014] In some embodiments, the present invention provides a composition comprising cabazitaxel, phosphatidylcholine, and sodium cholesterol sulfate for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, oral delivery is in the form of tablets or capsules. In a more preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0015] In some embodiments, the present invention provides a composition comprising cabazitaxel, phosphatidylcholine, and gugursterol for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, oral delivery is in the form of tablets or capsules. In a more preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0016] In some embodiments, the present invention provides a composition comprising cabazitaxel, phosphatidylcholine, and a gulosterol derivative for oral delivery to a subject. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human. In some embodiments, oral delivery is in the form of tablets or capsules. In a more preferred embodiment, the tablets and / or capsules comprise an enteric coating.

[0017] In some embodiments, the cabazitaxel composition of the present invention is administered in combination with other drugs. Drugs that can be administered in combination with the cabazitaxel composition include, but are not limited to, anticancer drugs such as doxorubicin, epirubicin, methotrexate, mitoxantrone, capecitabine, carboplatin, cisplatin, etoposide, 5-fluorouracil, cyclophosphamide, bendamustine, daunorubicin, bleomycin, gemcitabine, irinotecan, SN-38, mitoxantrone, cytarabine, erlotinib, imatinib, ibrutinib, palbociclib, bortezomib, abiraterone, bicalutamide, flutamide, temozolomide, etc. Antihypertensive drugs, such as dihydropyridines, antidepressants, and antihistamines; corticosteroids, such as prednisone, methylprednisolone, dexamethasone, budesonide, and hydrocortisone; antihistamines, such as diphenhydramine, chlorpheniramine, dextrochlorpheniramine, cetirizine, levocetirizine, loratadine, and desloratadine; and drugs for treating acid reflux, such as cimetidine, ranitidine, famotidine, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole.

[0018] The amount of cabazitaxel contained in the cabazitaxel composition according to the invention is not limited to any specific amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of cabazitaxel is from about 1% to about 90% of the total weight, preferably from about 2% to about 75% of the total weight, and more preferably from about 5% to about 50% of the total weight.

[0019] The content of phosphatidylcholine or phosphatidylglycerol in the cabazitaxel composition according to the invention is not limited to any specific amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of phosphatidylcholine is from about 1% to about 90% of the total weight, preferably from about 2% to about 80% of the total weight, and more preferably from about 3% to about 50% of the total weight.

[0020] The content of gulostrol, gulostrol derivatives, or sodium cholesterol sulfate in the cabazitaxel composition according to the invention is not limited to any specific amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of gulostrol, gulostrol derivatives, or sodium cholesterol sulfate is from about 0.1% to about 90% of the total weight, preferably from about 0.1% to about 50% of the total weight, and more preferably from about 0.1% to about 25% of the total weight.

[0021] definition To facilitate understanding of this invention, some terms and phrases are defined below: As used herein, the terms “composition,” “formulation,” or “dosage form” refer to a combination of an active pharmaceutical agent (e.g., an active pharmaceutical compound) with a carrier (inert or active) and excipients, making the composition particularly suitable for in vitro, in vivo, or ex vivo diagnostic or therapeutic use. When used herein to refer to a pharmaceutical agent, composition, or compound, the term “active pharmaceutical agent” means an agent that, upon administration or application, produces a beneficial, desired, or anticipated result. Administration can be a single or multiple doses, application, or ordination, and is not limited to a specific dosage form or route of administration. This term is not limited to any particular level of activity. For example, the level of activity of one active pharmaceutical agent dosage form need not be the same as that of another active pharmaceutical agent dosage form, as long as the active pharmaceutical agent in the dosage form is sufficiently active to provide an effective amount of the active pharmaceutical agent by application of the dosage form.

[0022] The terms “pharmaceutical” and “compound” are used interchangeably herein to refer to any mixture of atoms, molecules, or more complex compositions having specific properties. For example, an “active pharmaceutical” or “active compound” refers to any mixture of atoms, molecules, formulations, etc., that, upon administration or application, produces a beneficial, desired, or anticipated result.

[0023] As used herein, the terms “administration” or “application” refer to the act of supplying a drug, active pharmaceutical agent, or therapeutic treatment (such as the compositions of the present invention) to a physiological system (e.g., a subject or cells, tissues, and organs in vivo, in vitro, or ex vivo). Exemplary routes of administration to a subject (e.g., a mammal) may be oral, transdermal, ocular, nasal, etc. Administration may be performed once or multiple times, by application or oral administration, and is not limited to specific routes of administration.

[0024] As used herein, the term "combined administration" refers to the administration of at least two agents (e.g., two separate compositions containing different active agents) or therapies to a subject. In some embodiments, the combined administration of two or more agents or therapies is performed simultaneously. In other embodiments, the first agent / therapy is administered before the second agent / therapy. Those skilled in the art will understand that the dosage forms and / or routes of administration of the various agents or therapies used may differ. Those skilled in the art can readily determine the appropriate dosage for combined administration.

[0025] As used herein, the term "excipient" refers to an inactive ingredient (i.e., without pharmacological activity) added to an active ingredient formulation. Disintegrants, anti-adhesion agents, binders, plasticizers, fillers, coating agents, lubricants, preservatives, flow aids, fragrances, colorants, adsorbents, sweeteners, antioxidants, penetration enhancers, humectants, emulsifiers, ointment bases, acidifiers and / or alkalizers and / or buffers, gelling agents, and protectants are collectively referred to as "excipients".

[0026] As used in this article, the term "disease" refers to a state, sign, and / or symptom associated with any impairment of the normal state of a living animal or any of its organs or tissues that interrupts or alters normal function and may be a response to environmental factors.

[0027] As used herein, the term "treatment" or its grammatical equivalents encompass the improvement and / or reversal of symptoms of a disease (e.g., cancer) or a reduction in the risk of developing the disease. When used in the screening methods of this invention, a compound may be identified as a therapeutic compound if it improves any parameter associated with a disease. The term "treatment" refers to therapeutic treatment. For example, the population that may benefit from treatment with the compositions of this invention includes those who already have a disease and / or condition (e.g., cancer, or symptoms or pathology consistent with cancer).

[0028] As used in this article, the term "mammal" refers to a group of vertebrates that produce or secrete milk through mammary glands to nourish their offspring. Examples of mammals in this article include humans, dogs, felines, equines, cetaceans, and dolphins.

[0029] In the context of describing the invention (especially in the following claims), the terms “a,” “the,” and “the,” and similar designations, should be interpreted to cover both the singular and the plural, unless otherwise stated herein or the context clearly contradicts it. The terms “comprising,” “including,” “having,” and “containing” should be interpreted as open-ended terms (i.e., meaning “including but not limited to”), unless otherwise indicated. The use of any and all examples or exemplary expressions (e.g., “such as”) provided herein is intended only to better illustrate the invention and does not limit its scope, unless otherwise stated. No expression in the specification should be construed as indicating that any unclaimed element is essential for the implementation of the invention. Attached Figure Description

[0030] Figure 1 To show the blood concentration curve of cabazitaxel in mice over a period of time (Example 8).

[0031] Figure 2 To illustrate the blood concentration curve of cabazitaxel over a period of time after oral or intravenous administration to patients (Example 11). Detailed Implementation

[0032] This invention relates to a composition comprising a cabazitaxel formulation. In some embodiments, the invention includes administering the cabazitaxel composition to a subject, for example, for treating a disease. In some embodiments, the cabazitaxel-containing composition comprises a lipid, such as phosphatidylcholine or phosphatidylglycerol. In some embodiments, the cabazitaxel-containing composition comprises gulostrol or a gulostrol derivative or sodium cholesterol sulfate. In other embodiments, the composition comprises phosphatidylcholine or phosphatidylglycerol and / or gulostrol, a gulostrol derivative, or sodium cholesterol sulfate. In a preferred embodiment, the subject is a mammal; in a more preferred embodiment, the subject is a human.

[0033] Embodiments of the present invention have been described in the Summary of the Invention and in this Specific Description. Although the present invention has been described in conjunction with specific embodiments, the claimed invention should not be unduly limited to these specific embodiments.

[0034] Examples of phosphatidylcholine suitable for the compositions of the present invention include soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), dimyristoyl phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), and distearyl phosphatidylcholine (DSPC). Examples of phosphatidylglycerols include dimyristoyl phosphatidylglycerol (DMPG), distearyl phosphatidylglycerol (DSPG), and dipalmitoyl phosphatidylglycerol (DMPG).

[0035] Examples of gugursterol derivatives suitable for the compositions of the present invention include gugursterol laurate, gugursterol myristate, gugursterol palmitate, gugursterol stearate, gugursterol oleate, gugursterol linoleate, and gugursterol linoleate.

[0036] In some embodiments, the compositions of the present invention comprise antioxidants and / or stabilizers. Examples of antioxidants suitable for the compositions of the present invention include: α-tocopherol (vitamin E), α-tocopherol polyethylene glycol succinate (TPGS), ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium metabisulfite (SMB), propyl gallate, cysteine, and citric acid.

[0037] This invention provides a composition comprising cabazitaxel and delivers the composition to a subject, such as a human subject. Any suitable amount of cabazitaxel sufficient to produce the desired effect (e.g., therapeutic effect) can be used. In a preferred embodiment, a suitable amount of cabazitaxel refers to an amount that can be suitably incorporated into the tablets or capsules of this invention.

[0038] In a preferred embodiment, the tablet or capsule containing cabazitaxel and excipients contains cabazitaxel in a concentration between 10 mg and 2000 mg, for example, between 10 mg and 1000 mg or between 10 mg and 700 mg. In a preferred embodiment, the tablet or capsule containing cabazitaxel and excipients contains cabazitaxel in a concentration between 10 mg and 500 mg.

[0039] In some embodiments, the tablets or capsules containing cabazitaxel, lipids, and excipients contain lipids in the range of 10 mg to 5000 mg, for example, between 10 mg and 3000 mg, or between 10 mg and 2000 mg, and between 10 mg and 1000 mg. In a preferred embodiment, the tablets or capsules containing cabazitaxel and excipients contain lipids in the range of 10 mg to 500 mg.

[0040] In some embodiments, the tablets or capsules containing cabazitaxel, gulosterol, gulosterol derivatives, or sodium cholesterol sulfate and excipients contain gulosterol, gulosterol derivatives, or sodium cholesterol sulfate in a content of 1 mg to 500 mg, for example, 1 mg to 300 mg, 1 mg to 200 mg, and 1 mg to 100 mg. In a preferred embodiment, the tablets or capsules containing cabazitaxel and excipients contain gulosterol, gulosterol derivatives, or sodium cholesterol sulfate in a content of 1 mg to 500 mg.

[0041] The gulosterol or gulosterol derivatives used in this invention are Z-isomers, E-isomers, or mixtures of Z- and E-isomers. In a more preferred embodiment, the gulosterol or gulosterol derivatives are Z-isomers.

[0042] In some embodiments, the cabazitaxel composition contains a disintegrant. The disintegrant swells and dissolves upon contact with water, causing the tablet to disintegrate in the digestive tract and release the active ingredient for absorption. Disintegrants used in this invention include, but are not limited to, cross-linked polymers, such as croscarmellose sodium (also known as croscarmellose or croscarmellose), croscarmellose polyvinylpyrrolidone (also known as croscarmellose or croscarmellose); starch, clay, cellulose, and sodium glycolate starch.

[0043] In some embodiments, the cabazitaxel composition contains a binder. The binder binds the ingredients in the tablet together and improves free flowability by formulating the granules to the desired hardness and size. Examples of binders that can be used in this invention include, but are not limited to, cellulose, microcrystalline cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose, polyvinylpyrrolidone, polypropylene-polyethylene copolymer, magnesium aluminum silicate (Neuselin US2), sodium lauryl sulfate, glucose, sucrose, lactose, povidone, starch, gelatin, and sugar alcohols (e.g., xylitol, sorbitol, maltitol).

[0044] In some embodiments, the cabazitaxel composition contains a lubricant. The lubricant prevents the ingredients from clumping and adhering to the tableting or capsule filling machine. Examples of lubricants that can be used in this invention include, but are not limited to, stearic acid, magnesium stearate, calcium stearate, surfactants, polyethylene glycol, and vegetable oils.

[0045] In some embodiments, the cabazitaxel composition contains an absorption enhancer. The enhancer increases absorption by promoting the diffusion of the active ingredient or the solubility of the drug. Examples of absorption enhancers that can be used in this invention include, but are not limited to, vitamin E-PEG1000 succinate (TPGS), silicified microcrystalline cellulose (SMCC HD90), polyethylene glycol-polypropylene glycol-polyethylene glycol polymer (poloxam), stearic acid, oleic acid, magnesium stearate, calcium stearate, surfactants, propylene glycol, polyethylene glycol, and vegetable oils.

[0046] In some embodiments, the cabazitaxel composition contains a flow aid. Flow aids are commonly used to improve the flow properties of powder mixtures by reducing interparticle friction. Flow aids available in this invention include, but are not limited to, colloidal silica (e.g., fumed silica, Aerosil...). ® ), corn starch and magnesium carbonate.

[0047] In some embodiments, the cabazitaxel composition contains a diluent or filler. A diluent or filler is typically used to make up the volume when the drug itself is insufficient to produce a solid unit dosage form. Examples of diluents or fillers usable in this invention include, but are not limited to, glucose, lactose, starch, sorbitol, mannitol, microcrystalline cellulose, calcium hydrogen phosphate, calcium carbonate, and magnesium stearate.

[0048] In some embodiments, the cabazitaxel composition contains a plasticizer. Plasticizers are used to impart elasticity and flexibility to coating materials in tablets, and to determine the hardness and impart softness to the capsule shell in soft capsules. Plasticizers available in this invention include, but are not limited to, diacetylated monoglycerides, castor oil, polyethylene glycol, polypropylene glycol, triethyl citrate, and triacetin.

[0049] In some embodiments, the cabazitaxel composition comprises a coating material. The coating of the tablet or capsule protects the ingredients from deterioration caused by moisture in the air. Examples of coating materials used in this invention include, but are not limited to, hydroxypropyl methylcellulose (HMPC), synthetic polymers, polysaccharides, povidone, ethylcellulose, gelatin, and shellac.

[0050] In some embodiments, the cabazitaxel composition further comprises an enteric coating material. The enteric coating controls the drug release rate and determines the release site of the drug in the digestive tract. Examples of enteric coating materials that can be used in this invention include, but are not limited to, hydroxypropyl methylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), polymethyl methacrylate-co-methyl methacrylate, cellulose trimellitate acetate (CAT), polyvinyl acetate phthalate (PVAP), shellac, ethyl cellulose, and opadri. ® Enteric coating, methyl methacrylate copolymer or Eudragit ® and Acryl-EZE ® .

[0051] In some embodiments, the cabazitaxel composition contains a colorant. The colorant is added to improve the appearance and recognizability of the product. Examples of colorants available in this invention include, but are not limited to, FD, C, D, and C dyes and lakes.

[0052] Pharmaceutical formulations to which the compositions of the present invention are applicable include, but are not limited to, tablets, capsules, pills, and suspensions. For oral administration, preferred dosage forms include tablets, capsules, lozenges, and powders.

[0053] If necessary, compositions containing cabazitaxel, or cabazitaxel, phosphatidylcholine and / or gulostel, gulostel derivatives, or sodium cholesterol sulfate preparations can be encapsulated in enteric-coated tablets or enteric-coated capsules to prevent their degradation by gastric acid in the stomach. The term "enteric" refers to the small intestine, and enteric coating prevents the release of the drug before it reaches the small intestine. Most enteric coatings work by forming a surface that is stable at acidic pH but decomposes rapidly at higher pH.

[0054] In some embodiments, cabazitaxel, gulosterol, gulosterol derivatives, or sodium cholesterol sulfate are mixed with one or more excipients (e.g., croscarmellose sodium, polyvinylpyrrolidone, microcrystalline cellulose, and fumed silica (Aerosil)) and sieved to form granules. In some embodiments, the granules may also contain phosphatidylcholine. In some embodiments, these granules are mixed with a lubricant (e.g., stearic acid) and compressed into tablets. In a preferred embodiment, the tablets are sealed-coated with a polymer such as hydroxypropyl methylcellulose. In a particularly preferred embodiment, the sealed-coated tablets are further coated with a polymer such as methacrylic acid copolymer (Acryl-EZE). ® ) or hydroxypropyl methylcellulose polymer (Opadry ® Enteric coating is performed on the enteric-coated type.

[0055] In some embodiments, cabazitaxel, gulostelol, gulostelol derivatives, or sodium cholesterol sulfate are mixed with one or more excipients (e.g., microcrystalline cellulose) and an aerosol, and then sieved to form granules. In some embodiments, the granules also contain phosphatidylcholine. In some embodiments, these granules are mixed with microcrystalline cellulose, croscarmellose sodium, lactose, and poloxamer 188, and then compressed into tablets. In a preferred embodiment, the tablets are coated with a polymer (e.g., hydroxypropyl methylcellulose (HPMC), ethyl cellulose, or opadry). ® In a particularly preferred embodiment, the sealed-coated tablets are further coated with a polymer (e.g., methacrylic acid copolymer, Acryl-EZE). ® ), functional polymers (e.g., methacrylate-methyl methacrylate copolymer, Eudragit) ® Enteric coating is performed.

[0056] In some embodiments, the compositions of the present invention comprise antioxidants. Examples of antioxidants include, but are not limited to, α-tocopherol (vitamin E), α-tocopherol polyethylene glycol succinate (TPGS), ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium metabisulfite (SMB), propyl gallate, cysteine, citric acid, etc.

[0057] In some embodiments, the composition of the present invention contains about 0.1% to about 90% by weight, preferably about 0.5% to about 75% by weight, and more preferably about 1% to about 50% by weight of cabazitaxel.

[0058] In some embodiments, the amount of cabazitaxel in a single tablet or capsule is from 10 mg to 2000 mg, preferably from 10 mg to 1000 mg, and more preferably from 10 mg to 500 mg.

[0059] In some embodiments, the compositions of the present invention contain lipids comprising about 1% to about 90% of the total weight, preferably about 2% to about 80% of the total weight, and more preferably about 3% to about 50% of the total weight.

[0060] In some embodiments, the compositions of the present invention comprise from about 0.1% to about 90% by weight, preferably from about 0.1% to about 75% by weight, and more preferably from about 0.1% to about 50% by weight.

[0061] In some embodiments, the compositions of the present invention comprise from about 0.1% to about 90% by weight, preferably from about 0.1% to about 75% by weight, and more preferably from about 0.1% to about 50% by weight of a gugur sterol derivative.

[0062] In some embodiments, the compositions of the present invention comprise from about 0.1% to about 90% by weight, preferably from about 0.1% to about 75% by weight, and more preferably from about 0.1% to about 50% by weight. The compositions of the present invention can be administered in any dosage form and any system for delivering the active compound cabazitaxel in vivo. In some embodiments, the compositions of the present invention are delivered in a dosage form selected from tablets, chewable tablets, capsules, and soft gelatin capsules. In some embodiments, the compositions are formulated into the desired dosage form to achieve an immediate, sustained, or delayed release profile in vivo after administration.

[0063] Experimental Example Example 1 TPGS 1000 (5.0 g) and hydrogenated soybean phosphatidylcholine (HSPC) (15.0 g) were dissolved in ethanol (230 mL). Cabazitaxel (25.0 g) was then mixed and heated to 30–35 °C. Separately, Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using the cabazitaxel-HSPC solution via top spraying at an inlet temperature of 50–60 °C and a bed temperature of up to 27–35 °C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine Neusilin US2 (6.0 g) passed through a 330-mesh sieve, croscarmellose sodium (12.5 g), sodium dodecyl sulfate (2.5 g), poloxamer 188 (12.5 g), and hydrophilic fumed silica (Aerosil) (1.2 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then compressed into tablets.

[0064] HPMC 3 CPS (12.0 g) was dispersed in isopropanol (140 mL), and dichloromethane (90 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0065] Disperse Acryl EZE white (23.0 g) in purified water and stir for 30 minutes. Perform enteric coating using this mixture in an automated coating machine at an inlet temperature of 45-55°C and a bed temperature of 35-40°C. Dry the tablets at a bed temperature of 35-40°C for 20 minutes.

[0066] Example 2 TPGS 1000 (5.0 g) and gulostrol (15.0 g) were dissolved in ethanol (230 mL). Cabazitaxel (25.0 g) was then mixed and heated to 30–35 °C. Separately, Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using the cabazitaxel-gulostrol solution via top spraying at an inlet temperature of 50–60 °C and a bed temperature of up to 27–35 °C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine Neusilin US2 (6.0 g) passed through a 330-mesh sieve, croscarmellose sodium (12.5 g), sodium dodecyl sulfate (2.5 g), poloxamer 188 (12.5 g), and hydrophilic fumed silica (Aerosil) (1.2 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then compressed into tablets.

[0067] HPMC 3 CPS (12.0 g) was dispersed in isopropanol (140 mL), and dichloromethane (90 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0068] Disperse Acryl EZE white (23.0 g) in purified water and stir for 30 minutes. Perform enteric coating using an automated coating machine at an inlet temperature of 45-55 °C and a bed temperature of 35-40 °C. Dry the tablets at a bed temperature of 35-40 °C for 20 minutes.

[0069] Example 3 TPGS 1000 (5.0 g) and gugulasterol laurate (15.0 g) were dissolved in ethanol (230 mL). Cabazitaxel (25.0 g) was then mixed and heated to 30–35 °C. Separately, Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. Granulation was performed using the cabazitaxel-gugulasterol laurate solution via top spraying at an inlet temperature of 50–60 °C and a bed temperature of up to 27–35 °C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine granules of Neusilin US2 (6.0 g) passed through a 330-mesh sieve, croscarmellose sodium (12.5 g), sodium dodecyl sulfate (2.5 g), poloxamer 188 (12.5 g), and hydrophilic fumed silica (Aerosil) (1.2 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then compressed into tablets.

[0070] HPMC 3 CPS (12.0 g) was dispersed in isopropanol (140 mL), and dichloromethane (90 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0071] Disperse Acryl EZE white (23.0 g) in purified water and stir for 30 minutes. Perform enteric coating using an automated coating machine at an inlet temperature of 45-55 °C and a bed temperature of 35-40 °C. Dry the tablets at a bed temperature of 35-40 °C for 20 minutes.

[0072] Example 4 TPGS 1000 (10.0 g) and sodium cholesterol sulfate (5.0 g) were dissolved in ethanol (470 mL). Hydrogenated soybean phosphatidylcholine (HSPC) (25.0 g) was added until completely dissolved. Cabazitaxel (50.0 g) was then mixed and heated to 30-35°C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using cabazitaxel-HSPC-sod. The sodium cholesterol sulfate solution was processed using a top spray process at an inlet temperature of 50-60°C and a bed temperature of up to 27-35°C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine granules of Neusilin US2 (13.0 g) passed through a 330-mesh sieve, croscarmellose sodium (25.0 g), sodium dodecyl sulfate (5.0 g), poloxamer 188 (25.0 g), and hydrophilic fumed silica (Aerosil) (2.5 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then compressed into tablets.

[0073] HPMC 3 CPS (25.0 g) was dispersed in isopropanol (280 mL), and dichloromethane (190 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0074] Disperse 45.0 g of Acryl EZE white in purified water and stir for 30 minutes. Perform enteric coating with this mixture in an automated coating machine at an inlet temperature of 45-55°C and a bed temperature of 35-40°C. Dry the tablets at a bed temperature of 35-40°C for 20 minutes.

[0075] Example 5 TPGS 1000 (10.0 g) and gulostrol (5.0 g) were dissolved in ethanol (470 mL). Hydrogenated soybean phosphatidylcholine (HSPC) (25.0 g) was added until completely dissolved. Cabazitaxel (50.0 g) was then mixed and heated to 30-35 °C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using a top spray process with the cabazitaxel-HSPC-gulostrol solution at an inlet temperature of 50-60 °C and a bed temperature up to 27-35 °C. After spraying, the granules are dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine Neusilin US2 (13.0 g) passed through a 330-mesh sieve, croscarmellose sodium (25.0 g), sodium dodecyl sulfate (5.0 g), poloxamer 188 (25.0 g), and hydrophilic fumed silica (Aerosil) (2.5 g). The mixture is then lubricated with magnesium stearate for 5 minutes, and finally compressed into tablets.

[0076] HPMC 3 CPS (25.0 g) was dispersed in isopropanol (280 mL), and dichloromethane (190 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0077] Disperse 45.0 g of Acryl EZE (white) in purified water and stir for 30 minutes. Perform enteric coating with this mixture in an automated coating machine at a feed temperature of 45-55 °C and a bed temperature of 35-40 °C. Dry the tablets at a bed temperature of 35-40 °C for 20 minutes.

[0078] Example 6 TPGS 1000 (10.0 g) and gugursterol laurate (5.0 g) were dissolved in ethanol (470 mL). Hydrogenated soybean phosphatidylcholine (HSPC) (25.0 g) was added until completely dissolved. Cabazitaxel (50.0 g) was then mixed and heated to 30–35 °C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using a top spray process with the cabazitaxel-HSPC-gugursterol laurate solution at an inlet temperature of 50–60 °C and a bed temperature of up to 27–35 °C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine Neusilin US2 (13.5 g) passed through a 330-mesh sieve, croscarmellose sodium (25.0 g), sodium dodecyl sulfate (5.0 g), poloxamer 188 (25.0 g), and hydrophilic fumed silica (Aerosil) (2.5 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then the lubricated mixture was compressed into tablets.

[0079] HPMC 3 CPS (12.50 g) was dispersed in isopropanol (280 mL), and dichloromethane (190 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were then dried at a bed temperature of 35-40 °C for 30 minutes.

[0080] Acryl EZE white (22.50 g) was dispersed in purified water and stirred for 30 minutes. Enteric coating was then performed using an automated coating machine at an inlet temperature of 45-55°C and a bed temperature of 35-40°C. Each tablet containing 50 mg of cabazitaxel was dried at a bed temperature of 35-40°C for 20 minutes.

[0081] Example 7 TPGS 1000 (40.0 g) and gugursterol laurate (20.0 g) were dissolved in ethanol (1.9 L). Hydrogenated soybean phosphatidylcholine (HSPC) (100.0 g) was added until completely dissolved. Cabazitaxel (200.0 g) was then mixed and heated to 30-35 °C. Separately, Prosolve SMCC HD90 (240.0 g) and Neusilin US2 (80.0 g) were mixed and loaded into the hopper of the top spray assembly of the fluidized bed processor. The mixture was granulated using a top spray process with the cabazitaxel-HSPC-gugursterol laurate solution at an inlet temperature of 50-60 °C and a bed temperature of up to 27-35 °C. After spraying, the granules were dried, passed through a 30-mesh sieve, and then mixed in a mixer for 5 minutes with ultrafine granules of Neusilin US2 (54.0 g) passed through a 330-mesh sieve, croscarmellose sodium (100.0 g), sodium dodecyl sulfate (20.0 g), poloxamer 188 (100.0 g), and hydrophilic fumed silica (Aerosil) (10.0 g). The mixture was lubricated with magnesium stearate for 5 minutes, and then the lubricated mixture was compressed into tablets.

[0082] HPMC 3 CPS (100.0 g) was dispersed in isopropanol (1.14 L), and dichloromethane (760 mL) was added. The mixture was stirred for 25 minutes. The tablets were then sealed and coated in an automated coating machine at an inlet temperature of 40-45 °C and a bed temperature of 30-35 °C. The tablets were dried at a bed temperature of 35-40 °C for 30 minutes.

[0083] Disperse 180.0 g of Acryl EZE white in purified water and stir for 30 minutes. Use this mixture for enteric coating in an automated coating machine at an inlet temperature of 45-55°C and a bed temperature of 35-40°C. Dry each tablet containing 50 mg of cabazitaxel at a bed temperature of 35-40°C for 20 minutes.

[0084] All publications and patents mentioned in the foregoing specification are incorporated herein by reference. Various modifications and variations to the compositions described herein will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in conjunction with specific preferred embodiments, it should not be unduly limited to these specific embodiments. In fact, various modifications to the manner in which the invention is practiced will be apparent to those skilled in the art, and these modifications should be included within the scope of the following claims.

[0085] Example 8 Pharmacokinetics of Carbazate Tablets after Oral Administration in ICR (CD-1) Mice Five- to six-week-old ICR (CD-I) mice were fed a 19% protein rodent diet with free access to water. Mice were housed in the facility for at least 7 days prior to administration. Four mice were collected at each time point after administration, and two mice were collected before administration. A total of five time points were collected before and after administration (0.0, 0.5, 1.0, 2.0, 4.0, and 6.0 hours).

[0086] Weigh the cabazitaxel tablet (50 mg), crush it, and grind it into a powder using a glass mortar and pestle until free of lumps. Suspend the powder in purified water to a concentration of 2 mg cabazitaxel / mL. Sonicate the suspension for 2–3 minutes to ensure a homogeneous formulation before administration. The dosage is calculated based on the animal's body weight and is 20 mL / kg.

[0087] Using a 22-gauge stainless steel gavage needle, each animal was administered a single oral dose of 40 mg cabazitaxel / kg body weight. Following administration, blood samples were collected retro-orbital (under carbon dioxide anesthesia) and deposited into pre-labeled micro-blood collection tubes containing potassium EDTA (K2EDTA). Blood was collected once per mouse. Immediately after collection, the blood samples were gently inverted several times to ensure complete mixing with the anticoagulant, and then stored at 2–8 °C. Plasma was separated by centrifugation (10 minutes at 2000x g) and stored in frozen vials (-20 °C or lower) for subsequent analysis.

[0088] The concentration of cabazitaxel in plasma was quantitatively analyzed using C18 reversed-phase HPLC with a UV detector. Figure 1 ).

[0089] Example 9 Subacute toxicity of oral carbazide tablets in ICR (CD-I) mice ICR (CD-I) mice (5-6 weeks old) were fed a 19% protein rodent diet with free access to water. Mice were housed in the facility for at least 7 days prior to treatment. A total of 48 animals (24 males and 24 females) were randomly assigned to four groups (Table 1): A (control group), B (low-dose group), C (medium-dose group), and D (high-dose group). Control group mice were given water. Treatment group mice were given cabazitaxel daily for 5 consecutive days. All mice were sacrificed on day 29 for organ weighing and gross pathological examination.

[0090] Table 1. Dosage Groups

[0091] Cabazitaxel tablets were weighed and ground into powder before the start of the study and stored at 2–8°C. One portion of powder was weighed each day of administration and suspended in water at a concentration of 3 mg cabazitaxel / mL as the dosing formulation for the high-dose group mice. For the medium- and low-dose groups, the suspension was diluted to 2 mg / mL and 1 mg / mL, respectively. Cabazitaxel was administered orally via gavage using a 22 g stainless steel gavage needle. Mortality, clinical signs, body / organ weight, gross pathology, hematology, and blood chemistry were assessed.

[0092] Mortality: No deaths occurred in the control and low-dose groups throughout the study period. Three male mice died or were near death on day 8. Two male mice died in the high-dose group and one male mouse died in the medium-dose group. Three female mice also died in the high-dose group between days 8 and 11.

[0093] Clinical symptoms: Male mice in the medium-dose and high-dose groups developed clinical symptoms such as rough fur, dehydration, and arched back starting from day 5. By day 10, all surviving mice showed no clinical symptoms. Male mice in the low-dose and control groups showed no clinical symptoms. Female mice in the high-dose group developed clinical symptoms such as rough fur, dehydration, and arched back starting from day 5. By day 10, all surviving mice showed no clinical symptoms. Female mice in the low-dose, medium-dose, and control groups showed no clinical symptoms.

[0094] Body weight: In female mice, the high-dose group showed the greatest decrease in body weight on day 8 (an average decrease of 20% from day 1). The medium-dose group also showed a smaller decrease in body weight on day 5 (a decrease of 7.1% from day 1). In male mice, the maximum decrease in body weight was 14.8% in the high-dose group and 11.5% in the medium-dose group. At the end of the study, the remaining mice treated with cabazitaxel had body weights comparable to the control group.

[0095] Organ weight: The weight of animal organs (including liver, kidneys, heart, lungs, and spleen) was recorded at necropsy on day 29 and normalized to 20 grams of mouse body weight. All organ weights were comparable to those of the control group.

[0096] Gross pathology: No lesions or abnormalities were found in any major organs.

[0097] Hematology and blood chemistry: No abnormal changes were found in hematology and blood chemistry in any group.

[0098] Example 10 Effects of oral carbamate tablets on the survival of mice carrying P388 leukemia The CD2F1 mouse leukemia model carrying P388 has been widely used in preclinical evaluation to test the antileukemic activity of compounds (Dykes, DJ et al., 2008). In this model, untreated control mice survive for only about 9-11 days. Depending on the treatment effect, treated mice survive longer than control mice. Prolonged survival can serve as an endpoint for efficacy testing.

[0099] On the first day of the study, 4-6 week old CD2F1 mice were fed a 19% protein rodent diet and provided with free access to water. The mice were housed in the experimental facility for at least 7 days prior to use.

[0100] The mouse leukemia cell line P388 (logarithmic growth phase) was transferred from the culture flask to a sterile test tube and centrifuged at 200 times gravity acceleration (approximately 1000 rpm) and 2-8 °C for 5 minutes. The cells were washed twice with 10 mL of cold PBS and then resuspended in 5 mL of cold PBS. After staining with trypan blue, the cells were counted using a hemocytometer. 5 × 10⁶ cells were then... 6 / mL of cells were suspended in PBS. On day 0, 1×10⁶ cells were injected intraperitoneally at a dose of 0.2 mL. 6 Cells / mouse.

[0101] Crush and grind the cabazitaxel tablets (50 mg) into a powder free of lumps using a glass mortar and pestle. Suspend the powder in purified water at a concentration of 2 mg cabazitaxel / mL. Sonicate the suspension for 2–3 minutes to ensure a homogeneous suspension before administration at a dose level of 40 mg / kg / day. Dilute with purified water to a concentration of 1 mg cabazitaxel / mL at a dose level of 20 mg / kg / day. The dosage volume is calculated based on the individual animal's body weight, at a dose of 20 mL / kg.

[0102] Results: Compared with the untreated control group, treatment with a cumulative dose of 120 mg / kg of oral cabazitaxel significantly improved the survival rate of leukemia mice carrying P388 (Table 2).

[0103] Table 2. Summary of Dosage Levels, Dosing Schedule, and Median Survival

[0104] Example 11 Maximum tolerated dose (MTD) and pharmacokinetics of oral cabazitaxel tablets in patients with advanced solid tumors who have failed conventional therapy An open-label, non-randomized, multicenter, dose-escalation, single-dose study was conducted in patients with advanced solid tumors who had failed conventional therapy. Patients received a single oral dose of cabazitaxel lipid tablets (50, 100, 200, and 300 mg, corresponding to 1, 2, 4, and 6 tablets, respectively). The tablets were prepared according to Examples 6 and 7. Patients were initially enrolled in the lowest dose group, followed by higher dose groups. Blood, urine, and stool samples were collected at different time points for pharmacokinetic analysis.

[0105] Diagnostic and primary inclusion criteria: This study included patients with histopathologically / cytologically confirmed primary advanced solid tumors (e.g., breast cancer, head and neck cancer, lung cancer, melanoma, gastric cancer, colon cancer, or prostate cancer) for whom cabazitaxel monotherapy was feasible, or patients with advanced solid malignancies that were unresponsive to conventional treatment and had an ECOG performance status score of 0-2 with normal bone marrow, liver, and kidney function. A total of 15 patients were enrolled (3 patients each in the 50 mg, 100 mg, and 200 mg dose groups, and 6 patients in the 300 mg dose group).

[0106] To perform pharmacokinetic assessments, we collected a total of 20 blood samples (0.5 mL each) and 0.7 urine samples from each patient in each dose group at the time points specified in the protocol. Stool samples were collected prior to administration and for all patients in each dose group up to 24 hours later. Phoenix was used. ® WinNonlin ® The non-compartmental model of version 8.3 (Certara LP) was used to calculate the pharmacokinetic parameters of cabazitaxel.

[0107] Plasma: Cmax, AUCO-t, AUCO-∞, Tmax, AUC_%Extrap_obs, λz, Vd, Cl, and tl / 2 Urine: Ae0-72h, Rmax, Tmax, R Feces: Ae0-24h The plasma concentration-time curve of cabazitaxel is as follows: Figure 2 As shown in the table below, the pharmacokinetic parameters of cabazitaxel are summarized in the table below.

[0108] Table 3. Descriptive statistics of cabazitaxel (plasma) pharmacokinetics

[0109] Table 4. Descriptive statistics of cabazitaxel (urine) pharmacokinetics

[0110] Table 5. Descriptive statistics of carbatataxel (fecal) pharmacokinetics

[0111] The plasma pharmacokinetic characteristics of cabazitaxel were well characterized at all dose levels. Nonlinear behavior was observed at higher dose levels following a single 200 mg dose. The median time to reach peak plasma concentration after a single dose was 3 to 7 hours, and the mean terminal half-life was approximately 79 to 203 hours. A very small amount (i.e., <0.1%) of the drug was excreted in the urine within 72 hours after a single dose. Approximately 4% to 22% of the drug was excreted in the feces.

[0112] Most importantly, a single oral dose of cabazitaxel lipid tablets at dose levels of 100, 200, or 300 mg yielded mean AUCs of 889, 1187, or 1110 ng·h / mL, respectively. Intravenous cabazitaxel, at the recommended dose of 25 mg / mL... 2 (Jevtana) ® (Prescription information) When administered, the average AUC can reach 991 ng·h / mL.

[0113] Safety variables included adverse events (AEs), clinical laboratory parameters, vital signs, and physical examinations. All AEs reported during the study were included in the safety analysis. AEs were categorized by organ system according to the preferred terminology in MedDRA version 24.0. The maximum tolerated dose (MTD) of cabazitaxel lipid tablets was determined to be 300 mg.

[0114] References 1. Nightingale, G. and Ryu, J. Drug Forecast (2012), Vol. 37; 8:440-448.

[0115] 2. Paller, CJ and Antonarakis, ES. Drug Design, Development and Therapy (Drug Des.Devel. Ther.) (2011), 5;117-124.

[0116] 3. Palepu, N. US 2012 / 0065255 A1.

[0117] 4. Jevtana® (cabatasox) intravenous injection - Prescription information.

[0118] 5. Mita, AC, Figlin, R., Mita, MM (2012), Clin. Cancer Res. 18(24): 6574-6579.

[0119] 6. Abidi, AJ Pharmacology and Pharmcotherapeutics, (2013), 4:230-237.

[0120] 7. Calcagno, F., Nguyen, T., Dobi, E., Villanueva, C., Curtit, E., Kim, S., Montcuquet, P., Kleinclauss, F., Pivot, X., Thiery-Vuillemin, A., Clinical Medicine Insights: Oncology (2013), 7:1-12.

[0121] 8. Schwartzberg, LS, Navari, RM Adv. Ther. (2018). 35:754-767.

[0122] 9. Dykes, DJ and Waud, WR, L1210 and P388 leukemia in mice, Tumor Models in Cancer Research (2008), edited by BA Teicher © HumanaPress Inc., Totowa, NJ.

Claims

1. A composition, characterized in that, Containing cabazitaxel, and at least one lipid and / or gulosterol or gulosterol derivative or sodium cholesterol sulfate, in a sealed-coated and / or enteric-coated tablet or capsule.

2. The composition according to claim 1, characterized in that, The at least one lipid is selected from soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), dipalmitoyl phosphatidylcholine (DPPC), distearyl phosphatidylglycerol (DSPG), dipalmitoyl phosphatidylglycerol (DMPG), cholesterol (Choi), cholesterol sulfate and its salts.

3. The composition according to claim 1, characterized in that, The gugursterol derivatives are selected from gugursterol laurate, gugursterol myristate, gugursterol palmitate, gugursterol stearate, gugursterol oleate, gugursterol linoleate, and gugursterol linoleate.

4. The composition according to claim 1, characterized in that, The composition further contains one or more excipients selected from magnesium aluminosilicate, tocopherol polyethylene glycol succinate, silicified microcrystalline cellulose, magnesium stearate, croscarmellose sodium cellulose, sodium dodecyl sulfate, polyethylene glycol-polypropylene glycol-polyethylene glycol polymer, poloxamer 188, hydrophilic fumed silica, aerosols, and citric acid.

5. The composition according to claim 1, characterized in that, The sealing coating includes one or more polymers selected from hydroxymethylpropyl cellulose, methyl hydroxyethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone, sodium carboxymethyl cellulose, acrylate polymers, and polyethylene glycol.

6. The composition according to claim 1, characterized in that, The enteric coating comprises one or more polymers selected from hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, acrylate polymers, polyvinyl acetate phthalate, and methyl methacrylate copolymer.

7. The composition according to claim 1, characterized in that, The content of cabazitaxel in a single tablet or capsule is in the range of at least 20 mg to 1000 mg.

8. The composition according to claim 1, characterized in that, The lipid content in a single tablet or capsule is at least in the range of 10 mg to 1000 mg.

9. The composition according to claim 1, characterized in that, The content of the described guggul sterol or guggul derivative in a single tablet or capsule is at least 2 mg to 500 mg.

10. The composition according to claim 1, characterized in that, The content of sodium cholesterol sulfate in a single tablet or capsule is at least 2 mg to 500 mg.

11. The composition according to claim 1, characterized in that, The composition is a tablet or capsule, and the administration includes oral administration.

12. The composition according to claim 1, characterized in that, The composition includes oral administration to a subject.

13. The composition according to claim 12, characterized in that, The subjects were mammals.

14. The composition according to claims 12 and 13, characterized in that, The subjects were humans.

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