195 results about "Indirubin" patented technology

The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo.

The invention relates to pharmaceutical compositions and methods of treating inflammatory-related diseases associated with pro-inflammatory cytokine expression and / or reduced expression of anti-inflammatory cytokines. The method typically comprises administration of one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, such as, Meisoindigo and NATURA. Preferably the pharmaceutical composition comprises one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, an anti-inflammatory agent, and a pharmaceutically acceptable carrier.

The invention relates to pharmaceutical compositions and methods of treating inflammatory-related diseases associated with pro-inflammatory cytokine expression and / or reduced expression of anti-inflammatory cytokines. The method typically comprises administration of one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, such as, Meisoindigo and NATURA. Preferably the pharmaceutical composition comprises one or more compounds selected from isoindigo, indigo, indirubin, or derivatives thereof, an anti-inflammatory agent, and a pharmaceutically acceptable carrier.

A method for designing and synthesizing 7-azaindirubin and 7-azaisoindigo derivative and its medicinal use are disclosed. It changes indirubin and isoindigo nuclear-parent molecule atomic composition to form into compound. It also changes original molecule electric property. The process is carried out by coupling at different position by 7-azaindole and indole bi-molecule, inhibiting CDKs and CDKIs growth and breed and inducing CDKIs biological function. It can be used to treat malignant tumor, HIV and nervous system diseases.

The invention provides a method for preparing indigo naturalis, comprising the following steps of: a, placing leaves or stem leaves of strobilanthus (acanthaceae), indigo (polygonaceae) or woad (crucifer) into water with the pH value of 3.5-7 at the temperature of 25-60 DEG C, the mass ratio of water to the fresh leaves is 8-15, soaking for 24-48 hours, and filtering and removing leaf slag to obtain filtrate; b, introducing air into the filtrate for 0-30min, adding alkaline to regulate the pH value to be 9-10.5, introducing the air for 30-240min, adding lime milk, stirring to be uniform and standing, filtering to obtain precipitate, drying to obtain crude indigo, and refining the crude indigo to finally obtain the indigo naturalis. In the crude indigo prepared by adopting the method provided by the invention, contents of indigo blue and indirubin are higher, and product quality is good.

Compounds and compositions including 6-bromo-indirubin, 5-amino-indirubin and N-methyl-indirubins and related indirubin derivatives are provided that are useful as selective modulators of glycogen synthase kinase-3, cyclin-dependent protein kinases or aryl hydrocarbon receptors. Methods of inhibiting or modulating cell growth or cell cycling are provided using the compounds of the invention. In other aspects, compounds and methods for the treatment of protozoan-mediated diseases, Alzheimer's disease and diabetes are provided.

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). Indirubin derivatives (IRDs) potently reduce the viabilities of various cancer cells and affect kinase activities. IRDs disclosed herein provide new therapeutics for cancer and conditions regulated by the kinase activities.

A compound called NATURA, which is a derivative of Isoindigo is useful in aiding the general health of a patient and specifically is beneficial in preventing or treating cancer. This compound and other related Isoindigo, Indigo and Indirubin derivatives are designed such that the bioactivity or bioavailability of the compound is increased. Methods of synthesizing these derivatives is also taught. In addition, pharmaceutical compositions that include a therapeutically effective amount of at least one of these derivatives and a pharmaceutically acceptable carrier. A method for the use of these pharmaceutical compositions and compounds is taught, wherein a therapeutically effective amount is administered to an animal having solid tumor cancer. The pharmaceutical composition or compound can be re-administered to the animal until a desired treatment or result is accomplished.

The present invention relates to an application of indirubin derivative (IO) in the preparation of medicine for curing neural retrograde disease, specially, it relates to an application of indirubin derivative in the preparation of medicine for curing Parkinson's disease. Said invention uses the indirubin derivative as inhibitor and utilizes three kinds of mediated and died kinases of JNK / CDK5 / GSK3 beta which are inhibited by said indirubin derivative as clear target to develop the invented new medicine.

The present invention is preparation process and antitumor effect of N(1)-alkyl-3'-oximino indirubin derivative (I, JN-2528). The new synthesis process uses indirubin as initial material, and under the action of alkaline compound as promoter, indirubin is reacted directly with halohydrocarbon or other halide to obtain N(1)-alkyl indirubin derivative, which is then reacted with hydroxylamine to obtain N(1)-alkyl-3'-oximino indirubin derivative. The MTT and SRB process and transplanting C57 mouse Lewis lung cancer mold test proves the antitumor activity of N(1)-alkyl-3'-oximino indirubin. The compound shows extracorporeal and intracorporeal cancer inhibiting effect.

The invention discloses a supersaturated self-microemulsion, comprising Indirubin, an oil phase, a surfactant, a cosurfactant and a supersaturation accelerant. The invention further discloses a preparation method for the supersaturated self-microemulsion and an application of the supersaturated self-microemulsion in the preparation for a medicine treating tumour. The supersaturated self-microemulsion of the invention remarkably increases the bioavailability of Indirubin and has an important significance to enhance the anti-tumour effect of Indirubin.

The invention relates to the technical field of the traditional Chinese medicine and in particular to the quality standard of a pharynx-clearing dropping pill which is made from the raw materials of a natural indigo, liquorice, myrobalam, menthol, borneol, artificial cow-bezoar, polyglycol 6000. The item of physicochemical identification in the former quality standard is deleted; the thin layer identification of the borneol and the menthol, the thin layer identification of indigotin or indirubin and cholic acid or deoxycholic acid and the item of mensuration of bilirubin content are revised; the thin layer identification of the myrobalam, the layer identification of the liquorice and the item of the mensuration and detection of glycyrrhizic acid content are added, and the quantitative index of the liquorice content in each pill can not be less than 32 microgrammes, which is calculated according to the glycyrrhizic acid (C42H62O16). The invention improves the controllability of the quality standard of the pharynx-clearing dropping pill and further ensures the internal quality of the product, and the invention has great meaning for promoting the product sale and guaranteeing the medication safeness for the patient.

The invention provides an indigo prepared by adopting the froth-flotation method, which comprises the components by weight percentages as follows: 2.63%-5.51% of indigo blue and 0.13%-0.61% of indigo red. The invention also provides a preparation method and a device for the indigo. The preparation method for the indigo of the invention has the advantages that the operation and the management are convenient, the separation is not limited by environment or climate, and the running is stable and reliable. The preparation method is a novel technique for indigo separation; by adopting the novel technology for machining, the large scale production can be realized on the basis of ensuring the drug quality, in addition, the indigo product quality is increased; the preparation method has simple and convenient operation and low technical difficulty. The quality of the indigo which is prepared by the preparation method is higher than the pharmacopoeia standards obviously.

The present invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor with anti-cancer activity. More particularly, this invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor having excellent anti-cancer activity against human lung cancer cell, human fibro sarcoma cell, human colon cancer cell, human leukemia cell, human stomach cancer cell, human nasopharyngeal cancer cell and / or human breast cancer cell.

Methods and pharmaceutical compostions for treating or suppressing symptoms of neuroendocrine (NE) tumors comprising inhibiting the activities of GSK-3β of the cancer cells. Also disclosed are pharmaceutical compositions for the methods. Preferably, the pharmaceutical composition comprises Li+, SB216763, SB415286, indirubins, Paullones, Hymenialdisine, Azakenpaullone, Thienyl and phenyl α-halomethyl ketones, CHR 99021, AR-A014418, Bis-7-azaindolylmaleimides, CHR 98023, CHR-98014, and ZM336372, or a pharmaceutically acceptable salt or derivative thereof.

The present invention relates to an indirubin derivative having anticancer property by inhibiting cell proliferation as to human cancer cell line. More particularly, this invention provides the synthesis of indirubin derivative known as CDK(Cyclin-dependent kinase) inhibitor. Further, inhibition activity of proliferation as to human cancer cell line and apoptosis against induced-differentiation of said indirubin derivative are researched to develop a novel indirubin derivative having efficacious anticancer properties as to various human cell lines.

The invention relates to a method for preparing indirubin with simple and convenient operation, small pollution and little equipment investment. The method comprises the following technological steps:adding methanol with the quantity of 5-10 times of raw materials into the raw materials, extracting by ultrasonic for 1-3 times, extracting for 0.2-1 hour each time, merging extracting liquid, recovering the methanol by depressurization, concentrating, filtering liquor by a macroporous resin column, eluting with water firstly, removing impurities, then eluting with ethyl acetate, concentrating eluent, adopting chromatographic separation by an alumina column, eluting with chloroform-ethyl acetate, concentrating eluent, recrystallizing with methanol-acetone, washing, drying to obtain the indirubin. By adopting the invention to prepare the indirubin, the product purity is high and industrialization amplification is easy to realize.

The invention provides a method for controlling the quality of a Chinese traditional throat medicine. The method comprises the steps: (1) discriminating ginseng, radix trichosanthis and liquorice contained in the Chinese traditional throat medicine by the microscope discrimination method; (2) detecting vitriol in natrii sulfas exsiccatus by the barium chloride reagent precipitation method; (3) detecting natural indigo in the Chinese traditional throat medicine by the thin-layer chromatography, and comparing the natural indigo with indigotin and indirubin; (4) detecting borneol and menthol by the thin-layer chromatography; (5) detecting ginseng contained in the Chinese traditional throat medicine by the thin-layer chromatography, and comparing the Chinese traditional throat medicine with ginseng, ginseng saponin Rb1, ginsenoside Re and ginsenoside Rg1; (6) detecting liquorice contained in the Chinese traditional throat medicine by the thin-layer chromatography; and (7) detecting the content of andrographolide and dehydrolyzed andrographolide contained in the Chinese traditional throat medicine. The method used for controlling the quality of the Chinese traditional medicine overcomes the defects of the prior discrimination method that the specificity is not enough; the thin-layer chromatography is used for detecting natural indigo, borneol and menthol simultaneously, the sampling amount is difficult to grasp, and excellent separating effect is difficult to reach, the thin-layer chromatography can just detect limited ingredients, i.e. natural indigo, borneol and menthol, thus failing to effectively discriminate the Chinese traditional throat medicine; the prior discrimination method fails to measure the content of effective ingredients, and can not effectively control the defects of product quality. The method improves the specialty and the quality stability, and ensures security and effective use of the medicine by users.

The invention belongs to the field of natural product chemistry, and relates to extraction, separation and purification of natural products, in particular to a technical method for extracting high-purity total alkaloids from dyers woad leaf. The method for preparing indigo and indirubin from dyers woad leaf is mainly characterized by comprising the following steps of: drying, pulverizing and sieving dyers woad leaves; heating and extracting by reflux by an ethanol solution containing sodium hydroxide; recovering ethanol from filtrate; concentrating the filtrate, regulating the pH to be neutral by a hydrochloric acid solution, centrifuging; dissolving the precipitate by the hydrochloric acid solution, and centrifuging to obtain supernatant for later use; performing microfiltration on the supernatant in membrane separation equipment; loading the stock solution after microfiltration on a resin column for absorption, then eluting with water to remove water soluble impurities, discarding the water eluent; eluting with aqueous ethanol, collecting the eluent; and recovering ethanol from the eluent, concentrating and drying to obtain a dark red product. The method has the advantages of low production cost of the products, simple process route, smaller toxicity of the extraction solvent and short extraction cycle, and is suitable for application in industrial production. Based on the advantages, the method can further promote industrialized development of the dyers woad leaf extract as a multifunctional product such as a medicine, a health product and the like.

The invention discloses a method for detecting contents of baicalin, forsythin, indirubin and glycyrrhizic acid in Qingreling granules. The method comprises the following steps: pretreating the Qingreling granules to prepare a sample to be detected, and injecting the sample to be detected to a high performance liquid chromatograph for detecting to obtain a high performance liquid chromatogram of the sample to be detected; and calculating the contents of the baicalin, the forsythin, the indirubin and the glycyrrhizic acid in the sample to be detected according to the peak areas of corresponding absorption peaks in the high performance liquid chromatogram of the sample to be detected and a standard curve of each standard sample. The method disclosed by the invention can be used for measuring the components of the baicalin under the content determination items of the Qingreling granules in the first part of Pharmacopoeia of the People's Republic of China published in 2010, and also can be used for additionally measuring the content of the forsythin in fructus forsythiae, the content of the indirubin in folium isatidis and the content of the glycyrrhizic acid in liquorice and greatly improving the quality control standard of the Qingreling granules. Proved through content measurement methodology, the method completely conforms to the specification and is an advanced quality control method. The method can be used for shortening the detection time and reducing the detection cost.

The invention discloses a cytochrome P450 BM-3 D168R mutant enzyme as well as a method applying the enzyme to prepare indirubin. The enzyme adopts the directed evolution technique, and takes P450 BM-3 (F87V / A74G / L188Q / E435T) as a male parent, and is obtained by implementing the fixed-point saturation and mutation at the codon for the aspartic acid residue in position 168 of the sequence in the male parent gene through screening. The base sequence is shown as SEQ ID NO.1 in the sequence table, the codon at the original point is mutated to CGG from GAT, and the corresponding amino acid residue is mutated to arginine from aspartic acid. The P450 BM-3 D168R mutant enzyme of the invention takes indirubin as main acquired product when catalyzing indole, and the product shows obvious red color.

The invention provides a radix isatidis particle quality control method and aims to measure arginine content and indirubin content at the same time by an HPLC (high-performance liquid chromatography). The radix isatidis particle quality control method comprises the following steps of respectively preparing an arginine standard sample, an indirubin standard sample and a radix isatidis particle test sample; performing comparison calculation to obtain the arginine content and the indirubin content of the radix isatidis particle test sample by the HPLC. The control method for the radix isatidis particle content is easy to operate; a quantification control requirement on effective components in a traditional Chinese medicinal product in which the type of the effective component is complicated is met, so that the quality level of the product is improved; the practice shows that the arginine content of radix isatidis particles is limited to be more than or equal to 12.5 mg / g in each gram of particles and the indirubin content of the radix isatidis particles is limited to be 0.12 mg / g, and the arginine content and the indirubin content which are limited can be used as quality control standards on the radix isatidis particles.

The invention relates to a Chinese medicinal compound preparation arsenic tetrasulfide-tanshinone-indirubin and a preparation method thereof and application thereof in preparing antineoplastic agents. The Chinese medicinal compound preparation comprises the active ingredients of arsenic tetrasulfide, indirubin and tanshinone IIA in a weight ratio of 1-10:1:1. The Chinese medicinal compound preparation arsenic tetrasulfide-tanshinone-indirubin can be applied to the preparation of the antineoplastic agents. Pharmacological experiment results show that the Chinese medicinal compound preparation arsenic tetrasulfide-tanshinone-indirubin can treat various neoplastic diseases.

The invention discloses a method for preparing indigo naturalis. The method comprises the following steps: selecting leaves or stem leaves of jacobinia suberecta baphicacanthus cusia, polygonaceae plant indigo or crucifer isatis tinctorial, extracting in hot water, and filtering to remove leave residues to obtain filtrate; adding an acid solution into the filtrate, and performing hydrolysis; adding an alkali solution to adjust the pH value of the solution to be 6-8 after hydrolysis is completed, standing, removing supernate to obtain precipitate, washing to be neutral, and drying to obtain theindigo naturalis. According to the preparation method, a new way for preparing indigo naturalis is provided, the influence of CaCO3 can be avoided, the labor intensity for preparing indigo naturaliscan be greatly reduced, and the production cycle can be shortened. By utilizing the preparation method, the content of indigo is 30.51-54.84 percent, the content of indirubin is 5.41-13.52 percent, the content of indigo is increased by 10-20 times that by a traditional processing method, and the content of indirubin is increased by 20-30 times that by the traditional processing method, and the quality of indigo naturalis products realizes qualitative leap.

The indirubin dripping pill containing indirubin 1-12 mg and proper amount of dripping pill medium in each pill. The dripping pill medium is one or two of polyglycol-6000, polyglycol-4000, polyoxyethylene monostearate, sodium stearate, glycerin, gelatin, poloxamer, stearic acid, glycerin monostearate and insect wax. The preparation process of the indirubin dripping pill includes melting and mixing indirubin and dripping pill medium, dropping at 60-120 deg.c into condensating agent, and eliminating condensating agent. The condensating agent is one or two of dimethyl silicon oil, liquid paraffin, tea seed oil and rape seed oil. The indirubin dripping pill is dark red. The indirubin dripping pill is used in treating chronic granulocyte leukaemia, and has the features of less side effect, low dosage, high medicinal effect, no obvious inhibition on marrow of patient, etc.

Disclosed is an indirubin phosphatide compound and process for preparation, wherein the compound consists of indirubin and phosphatide by the mol ratio of 1 : 1-15, the indirubin phosphatide compound has good stability, stronger lipophilicity and superior property in medicament absorption degree, speed of action, and effect duration, it can be prepared into various oral dosages.

The present invention discloses a kind of freeze dried isatis root powder for injection and its preparation process and the freeze dried isatis root powder for injection is prepared with HP-beta-CD inclusion of extracted capillary artemisia oil in 0.5-2 weight portions, purified extract of isatis root, capillary artemisia and licorice in 30-50 weight portions, and medicinal supplementary material. The present invention features that the extract contains indirubin more than 40 ppm and indigo more than 42 ppm. Pharmaceutical experiment results show that the freeze dried isatis root powder for injection of the present invention has even high pharmaceutical effect.

The invention discloses a 1'-thio-aza indirubin compound, application and a preparation method thereof, belonging to the field of medical technology. The preparation method of the compound comprises the steps of: respectively condensing 5-substituted, 6-substituted, 7-substituted isatin derivatives or 1-alkyl-7-azaindole-2,3-dione with thieno-(2,3-b)-pyridine-3-ketone or benzo-3(2H)-ketone to obtain a 1'-thio-aza indirubin compound in which R=O, wherein sodium carbonate is used as a catalyst; and reacting the 1'-thio-aza indirubin compound in which R=O with hydroxylamine to obtain a 1'-thio-aza indirubin compound in which R=NOH. The invention also relates to the application of the compound in the preparation of antineoplastic agents, acceptable salts in pharmacy synthesized by the compound with inorganic acid, organic acid or amino acid. The compound of the invention can suppress or kill tumor cells, have the character of anti-tumor activity and can be used for preparing medicines for treating tumors.