39 results about "Homoharringtonine" patented technology

An application of the cephalotaxine ester, especially the harringtonine and homoharringtonine, in preventing and treating the roundworm diseases of plant is disclosed.

The present invention relates to a new technique formed from polysaccharides of kelp (PK), which has function of anticancer and increasing immunity, and new nanoparticles (NP) and special liposome (SSL), which contained natural anticancer drug their preparation. Also, the present invention is aimed at the overall improvement of therapeutic efficacy of anticancer drugs, including Homoharringtonine (HHT), Curcumol (CUR), Eelemene (ELE) and Camptothecin (CPT) by NP and SSL. NP improves the anticancer therapeutic efficacy of HHT, CUR, ELE and CPT by using PK as polymer. PK can improve the anticancer therapeutic index and decrease side effect of free anticancer drugs. Also, PK has the function of increasing immunity. The present invention disclosed a process for making a polysaccharide of kelp (PK), PK-Drug-NP and special PK-anticancer drug-containing sterically stabilized liposomes (PK-Drug-SSL).

A process for extracting the harringtonine and homoharringtonine from the small twigs and leaves of fortune plumyew through pulverizing, alkalizing with diluted ammonia water, supercritical Co2 fluid extracting, separating common cephalotaxus alkaloid, chromatography, recovering the harringtonine mixture, and respectively recrystallizing.

The present invention provides a new method for extracting Homoharringtonine (HHT) by culture cells or culture plant tissues. Also, disclosed are methods of obtaining HHT from semi-synthesis and biosynthesis. The present invention disclosed that HHT combined with some botanical drugs could induce cancer cells to resemble normal cells. To add some botanical drugs combined with HHT can significantly increase anticancer effects of HHT. These drugs include Matrine (MAT), Guanzhongsu (GU), Maidongsu (MU), and Indirubin (IND). The experimental data showed that above drugs have strong synergisms effects for treating leukemia and other cancer cells and more safe.

An orally-applied dropping pill of anticancer alkaloid contains camptothecine or taxol or harringtonine or homoharringtonine and matrix of dropping pill. Its preparing process includes proportioning,thermal fusion, stirring, and dropping it at 60-150 deg.c in condensing agent at speed of 20-100 drops per min, and removing condensing agent.

The present invention is directed to compositions and methods for the treatment of patients with cephalotaxines, for example, homoharringtonine. The invention is also directed to improvements in the purity, manufacturing process, formulation and administration of homoharringtonine for the treatment of cancer and other aberrant cellular diseases. The invention also provides methods and compositions for antiparasitic, antifungal, antiviral and antibacterial treatments.

Provided herein is a combination product comprising a Bcl-2 / Bcl-xL inhibitor and a chemotherapeutic agent, in particular a Bcl-2 / Bcl-xL inhibitor of formula (I-A) and homoharringtonine or an active derivative thereof, in free or pharmaceutically acceptable salt or solvate form. Provided herein is also the use of the aforementioned combination for the preparation of a medicament for the prevention and / or treatment of cancer, in particular of hematological malignancies, and to a method for the prevention and / or treatment of cancer, in particular of hematological malignancies, using the aforementioned combination.

The invention provides an extraction method of Homoharringtonine through microbial fermentation and application of Homoharringtonine. The extraction method of Homoharringtonine comprises the following steps: (1) separating a microbial fermentation product to obtain thalluses and fermentation broth of which thallus is removed and carrying out organic solvent extraction and redissolution on the fermentation broth of which thallus is removed or thalluses to obtain crude extract liquid; (2) adsorbing the crude extract liquid with macroporous resin or activated carbon and carrying out desorption to obtain an alkaloid crude extract; and (3) performing high performance liquid purification on the obtained alkaloid crude extract to obtain Homoharringtonine; or firstly performing column chromatography on silica gel for purifying the obtained alkaloid crude extract to obtain crude Homoharringtonine and then performing high performance liquid phase purification on the obtained crude Homoharringtonine to obtain Homoharringtonine. According to the extraction method, since a microbial fermentation product is used as raw material, the cost is low; the process is simple and microbial thalluses or fermentation broth can be purified to obtain Homoharringtonine with high efficiency and high yield.

The invention discloses a medicine composition for therapy of allergic rhinitis, which includes Helikaurolide A and homoharringtonine as active components, wherein the Helikaurolide A and the homoharringtonine have excellent effects on therapy of the allergic rhinitis.

The invention relates to application of homoharringtonine in preparing medicine for preventing foot-and-mouth disease virus infection, and belongs to the technical field of veterinary medicine. By means of the application, highly effective, safe and quality-controllable anti-foot-and-mouth disease virus medicine can be provided for further controlling spread of a foot-and-mouth disease.

The present invention relates to a combined product. The combined product contains a Bcl-2 / Bcl-xL inhibitor and a chemotherapeutic drug, in particular the Bcl-2 / Bcl-xL inhibitor which has a formula I-A and is in the form of free or pharmaceutically acceptable salt or solvate, and homoharringtonine or active derivatives thereof. The invention also relates to application of the combined product in the preparation of a drug for preventing and / or treating cancer, in particular hematological malignancies, and a method for preventing and / or treating the cancer, in particular the hematological malignancies by using the combined product.

The application discloses application of homoharringtonine in the treatment of colorectal tumors. Homoharringtonine can inhibit the growth of colorectal tumor cells. It is verified herein that homoharringtonine can inhibit the growth of colorectal tumor cells. Homoharringtonine can inhibit evidently the proliferative abilities of two colorectal tumor cells HT29 and SW620; after homoharringtonine act, the expression of cyclins CDK2, CDK4, CDK6, CyclinD1 and CyclinE is reduced; when acting, homoharringtonine can inhibit the expression of apoptosis inhibitory protein Bcl-2 and promote the expression of apoptosis inhibitory proteins Bax and Cleaved-PARP. It is discovered herein that homoharringtonine can inhibit biological functionality of colorectal tumor cell lines SW620 and HT29; and homoharringtonine can treat colorectal tumors.

The invention discloses a method for extracting homoharringtonine. The method includes the steps that a dried and pulverized cephalotaxus sinensis raw material is extracted with methanol-chloroform mixed liquor, filtration is performed, filter liquor is concentrated to obtain extract, chloroform precipitation is performed, filtration is performed, filter liquor is concentrated at 65-70 DEG C to obtain crude homoharringtonine, and the crude homoharringtonine is subjected to reversed-phase column chromatography, concentration, extraction, recrystallization, separation and purification to obtainfinished homoharringtonine, wherein the homoharringtonine content is larger than 98%. The method is simple and easy to operate, short in production cycle, low in cost, high in yield, and suitable forindustrial application and market promotion.

The present invention belongs to the field of natural medicine and pharmaceutical chemistry and specifically relates to novel aminated homoharringtonine derivatives of formula (I) and a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments.

The invention belongs to the technical field of biological medicines, and relates to a pharmaceutical composition containing homoharringtonine (HHT) and an application of the pharmaceutical composition, in particular to the pharmaceutical composition containing the homoharringtonine and an application of the pharmaceutical composition to preparation of a medicine for treating leukemia. The invention particularly relates to an application of a pharmaceutical composition of HHT and a Bcl-2 inhibitor Venetoclax to treatment of AML or an application of the pharmaceutical composition of HHT and an FLT3 inhibitor (midostaurin, sorafenib, gilteritinib, crenolanib or quizartinib) to preparation of a medicine for treating AML of FLT3-ITD mutation. The molar ratio of the homoharringtonine to the venetoclax serving as the Bcl-2 inhibitor ranges from (1: 5) to (4: 1), and the molar ratio of the homoharringtonine to the FLT3-ITD ranges from (1: 5) to (5: 1). The components of the composition can be used at the same time or in any sequence.

The invention discloses an oral solid pharmaceutical composition in a micronized form by using a solid preparation with a micronized homoharringtonine derivative as an active component. The composition comprises a pharmacological active agent with an effective dosage, crospovidone or polyvinylpyrrolidone, and an oral solid pharmaceutical composition used for a pharmacological active agent. The oral solid pharmaceutical composition has an excellent in-vitro dissolution rate, and has good dissolution rates in a variety of pH conditions, so that good absorption of medicines in different populations can be effectively ensured, and the problems that an existing homoharringtonine derivative drug is not easily dissolved out in an in-vivo gastrointestinal environment and then in-vivo bioavailability of drugs is reduced and efficacy is influenced can be solved.

The present invention relates to a pharmaceutical composition for treating acute myelogenous leukemia. The pharmaceutical composition comprises active ingredients of homoharringtonine and a Wee1 kinase inhibitor, wherein a weight ratio of the homoharringtonine to the Wee1 kinase inhibitor is 1:10 to 10:1. The pharmaceutical composition is significantly effective for treating leukemia, particularlyfor chronic myelogenous leukemia or acute myelogenous leukemia, and provides a whole novel approach to a co-administration regimen for development and treatment of the leukemia.

The present invention discloses a dual-drug co-delivery system, a preparation method therefor and use thereof, the dual-drug co-delivery system being prepared from raw materials comprising a block copolymer, Homoharringtonine and Doxorubicin hydrochloride. The dual-drug co-delivery system provided by the present invention has a stronger killing effect on various hematologic tumors and solid tumor cells, can provide a feasible drug delivery system for inhibiting tumor growth and leukemia treatment, and has broad prospects.

A method of treatment of a host with a cellular proliferative disease, comprising contacting the host with a cephalotaxine and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, is described. In some embodiments, the cephalotaxine comprises homoharringtonine (cephalotaxine, 4-methyl-2-hydroxy-2-(4-hydroxy-4-methyl pentyl)butanediocate ester). Antiproliferative agents of the invention comprise alkylating agents, intercalating agents, metal coordination complexes, pyrimidine nucleosides, purine nucleosides, inhibitors of nucleic acid associated enzymes and proteins, and agents affecting structural proteins and cytoplasmic enzymes.

The invention provides an extraction method of Homoharringtonine through microbial fermentation and application of Homoharringtonine. The extraction method of Homoharringtonine comprises the following steps: (1) separating a microbial fermentation product to obtain thalluses and fermentation broth of which thallus is removed and carrying out organic solvent extraction and redissolution on the fermentation broth of which thallus is removed or thalluses to obtain crude extract liquid; (2) adsorbing the crude extract liquid with macroporous resin or activated carbon and carrying out desorption to obtain an alkaloid crude extract; and (3) performing high performance liquid purification on the obtained alkaloid crude extract to obtain Homoharringtonine; or firstly performing column chromatography on silica gel for purifying the obtained alkaloid crude extract to obtain crude Homoharringtonine and then performing high performance liquid phase purification on the obtained crude Homoharringtonine to obtain Homoharringtonine. According to the extraction method, since a microbial fermentation product is used as raw material, the cost is low; the process is simple and microbial thalluses or fermentation broth can be purified to obtain Homoharringtonine with high efficiency and high yield.

The invention discloses a detection apparatus and method for cancer treatment effect of harringtonine. According to the invention, the peak value of the signal-to-noise ratio of harringtonine with unknown drug effect is compared with the peak value of the signal-to-noise ratio of a frequently used cancer treatment drug, i.e., cisplatin, and the drug effect and dosage of harringtonine are obtained in comparison with the known drug effect and dosage of cisplatin. The detection apparatus and method provided by the invention have the characteristics of high detection efficiency, good accuracy and capacity of providing reliable bases for safe usage of harringtonine so as to ensure safety of patients.

The present invention is directed to compositions and methods for the treatment of patients with cephalotaxines, for example, homoharringtonine. The invention is also directed to improvements in the purity, manufacturing process, formulation and administration of homoharringtonine for the treatment of cancer and other aberrant cellular diseases. The invention also provides methods and compositions for antiparasitic, antifungal, antiviral and antibacterial treatments.

The present invention relates to the fields of natural medicine and medicinal chemistry, and relates to, as represented by formula (I) and formula (II), a novel acylated derivative of homoharringtonine or a pharmaceutically acceptable salt thereof, a method for preparing the compounds, a pharmaceutical composition comprising the compound, and an application thereof in preparing an antitumor medicament.

The invention relates to a plant source preparation for antiviral infection for livestock and poultry, in particular to the application of HHT as a broad-spectrum antiviral preparation. The present invention finds for the first time that homoharringtonine (HHT) has broad-spectrum and high-efficiency antiviral activity, and can efficiently inhibit 9 kinds of viruses (VSV, NDV, PEDV, TGEV, AIV, HSV‑1, PRV, PRRSV, FMDV) ) to infect host cells and animals (chicken, chicken embryos, pigs, etc.), significantly reduce the amount of virus in the animal body, and alleviate the symptoms of infection, providing safe and reliable new biological agents for the breeding industry. The invention provides the basis and possibility for developing broad-spectrum and high-efficiency antiviral new drugs, and provides a new safe and reliable technical means for ensuring the sustainable development of agriculture and animal husbandry and human health. It has far-reaching practical significance for developing traditional medical resources and promoting the cause of traditional Chinese medicine in our country.

The present invention discloses the new use of homoharringtonine and harringtonine in inhibiting vasculariztion. Research probes the vasculariztion inhibiting effect of homoharringtonine and harringtonine. The technological scheme is that homoharringtonine and harringtonine are used in preparing medicine for prevention and / or treatment of inhibiting vasculariztion with the dosage being 0.03-0.1 mg / kg body weight / day and 0.05-0.1 mg / kg body weight / day separately. The present invention uses the vasculariztion as the target of treating diseases and has the advantages of treatment specificity of pointing newly formed vessel; small dosage, high treating effect and less side effect owing to the direct action of medicine to vascular endothelial cell; and less medicine resistance owing to relatively stable endothelial cell gene expression.

A method of treatment of a host with a cellular proliferative disease, comprising contacting the host with a cephalotaxine and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, is described. In some embodiments, the cephalotaxine comprises homoharringtonine (cephalotaxine, 4-methyl-2-hydroxy-2-(4-hydroxy-4-methyl pentyl)butanediocate ester). Antiproliferative agents of the invention comprise alkylating agents, intercalating agents, metal coordination complexes, pyrimidine nucleosides, purine nucleosides, inhibitors of nucleic acid associated enzymes and proteins, and agents affecting structural proteins and cytoplasmic enzymes.

The present invention provides a new method for extracting Homoharringtonine (HHT) by culture cells or culture plant tissues. Also, disclosed are methods of obtaining HHT from semi-synthesis and biosynthesis. The present invention disclosed that HHT combined with some botanical drugs could induce cancer cells to resemble normal cells. To add some botanical drugs combined with HHT can significantly increase anticancer effects of HHT. These drugs include Matrine (MAT), Guanzhongsu (GU), Maidongsu (MU), and Indirubin (IND). The experimental data showed that above drugs have strong synergisms effects for treating leukemia and other cancer cells and more safe.

The invention relates to the field of pharmaceutical chemistry and in particular discloses a method for purifying homoharringtonine. The method for purifying homoharringtonine comprises the following steps: dissolving crude homoharringtonine by a mobile phase, taking silica gel as a stationary phase and taking a mixed solution of ethyl acetate, normal hexane and DIEA (Diisopropylethylamine) as the mobile phase to carry out column chromatography, collecting a chromatographic solution containing homoharringtonine, and concentrating the chromatographic solution into solid; dissolving the solid by using ethyl acetate, then adding normal hexane or n-heptane, uniformly mixing, standing and crystallizing, carrying out suction filtration, drying filter cake to obtain homoharringtonine solid. According to the method for purifying homoharringtonine, the common silica gel is used for replacing aluminum oxide in reversed phase chromatography and is taken as the stationary phase; the proper mobile phase is selected by taking the stationary phase as a basis and cooperates with subsequent optimally-matched organic solvents for re-crystallizing; the purity of the purified homoharringtonine is greater than 99.5%; the re-crystallizing yield is increased to 90-95%; the operation is simplified; the cost is lowered; the industrial production is facilitated.