31 results about "Indirubin" patented technology

The invention discloses a method for directionally preparing indigo blue or indirubin by biocatalytically converting indoleglycoside fermentation liquor, which is characterized in that beta-glucosidase Asbg1 and flavin-dependent monooxygenase MaFMO are combined, and the indoleglycoside fermentation liquor is used as a substrate to directionally prepare the indigo blue or indirubin. A glucose dehydrogenase (GDH)-mediated NADPH circulating system is introduced as a process supply cofactor, and then process conditions are optimized and regulated, so that a process for directionally preparing the indigo blue or indirubin by taking the indole glycoside fermentation liquor as a substrate is established, and the directional preparation of the indigo blue or indirubin is realized. The process provides a method for realizing green and efficient directional preparation of indigo blue or indirubin.

The invention discloses a method for synchronously, efficiently and directionally preparing indirubin and tryptanthrin by using a blue grass raw material, which comprises the following steps: pretreating blue grass to obtain blue grass powder or slurry; adding water into the blue grass powder or slurry, then adding a precursor substance, and carrying out ultrasonic or microwave treatment; according to different target products, static conversion or dynamic conversion can be carried out, or static conversion or dynamic conversion is carried out after microorganisms producing cellulase and oxygenase are inoculated, and the products are subjected to post-treatment such as drying and grinding. The method is simple to operate, high in processing efficiency, flexible in product scheme, low in production cost and suitable for large-scale production. The content of the indole alkaloid in the obtained material rich in the indole alkaloid is 1%-10%; the yield of indirubin reaches 5.64 mg / g, which is 21.7 times that of the traditional process; and the tryptanthrin yield reaches 7.68 mg / g, which is 10.8 times that of the traditional process.

To provide a method for treating a disease. [Solution] The present invention relates to compounds, compositions and methods for modulating skin pigmentation in a subject, and for treating or preventing UV-induced skin damage, erythema, skin aging, sunburn and hyperpigmentation. The compounds, compositions and methods of the present invention generally include compounds derived from Malassezia, including malassezin and indirubin, and / or their chemical analogues. Other uses of the compounds and compositions disclosed herein include, but are not limited to, improvement of hyperpigmentation caused by hyperpigmentation disorders, including melanocyte apoptosis, and modulation of aromatic hydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogeneration, melanosome transport, melanocyte activity and melanin concentration.

In the process of producing indigo naturalis by taking strobilanthes cusia as a raw material, a very unpleasant smell is generated, a large amount of alkaline wastewater is discharged, and serious environmental pollution is caused. Therefore, development of a more environment-friendly production process and a higher value-added strobilanthes cusia extract is extremely urgent. The invention innovatively provides a green and efficient production process, namely integrally producing the indigo strobilanthes extract and the phenolic acid extract with higher additional values through endogenous enzymatic conversion coupled membrane separation and freeze drying technologies. Through an endogenous enzyme conversion process, the indigo extract with indigo content 20 times and indirubin content 1.8 times higher than that of traditional indigo can be prepared within one day. The phenolic acid extract is recovered from the indigo extract production wastewater by adopting membrane separation and freeze drying processes, and meanwhile, zero discharge of the wastewater can be realized. The prepared indigo extract shows a more excellent dyeing effect on pure cotton poplin than an Indian natural indigo extract. In addition, the prepared phenolic acid extract shows excellent inhibitory activity (IC50 = 32 [mu] g / mL) on staphylococcus aureus, and the wound healing rate of mice exceeds 98%. The method lays a foundation for high-valued and comprehensive utilization of strobilanthes cusia resources, and is of great significance to extension and sustainable and healthy development of a strobilanthes cusia industrial chain.

The invention discloses a platelet increasing capsule characteristic chromatogram and a construction method and application thereof, and belongs to the technical field of quality control of traditional Chinese medicine compound preparations. According to the method, 13 control components including gallic acid, catechin, paeoniflorin, forsythiaside B, benzoic acid, astragalus smicus glycoside, forsythin, arctiin, liquiritigenin, benzoyl paeoniflorin, paeonol, arctigenin and indirubin are selected, a high performance liquid chromatography-mass spectrometry technology is applied, multiple batches of preparation samples are analyzed, and the content of the components in the preparation samples is determined. And establishing a characteristic spectrum of the chemical components. Compared with a traditional method, the technology has good precision and reproducibility, the data result is accurate and reliable, meanwhile, the technology can identify the 13 components at the same time under the same chromatographic condition, the analysis efficiency is remarkably improved, synchronous monitoring of multiple effective components is achieved, and the consistency and stability of the preparation quality can be guaranteed.

The present invention relates to compounds, compositions, and methods for modulating skin pigmentation and treating or preventing UV-induced skin damage, erythema, aging of the skin, sunburn, and hyperpigmentation in a subject. The compounds, compositions, and methods of the present invention generally involve Malassezia-derived compounds, including malassezin and indirubin, and / or chemical analogs thereof. Other applications of the compounds and compositions disclosed herein include, but are not limited to, improving hyperpigmentation caused by a hyperpigmentation disorder, inducing melanocyte apoptosis, and modulating arylhydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogenesis, melanosome transfer, melanocyte activity, and melanin concentration.

This invention provides a controlled-release pharmaceutical composition containing indigo naturalis or its main active ingredient, a method for its preparation, and its application. The controlled-release pharmaceutical composition comprises microspheres, each microsphere containing the active ingredient and one or more pharmaceutically acceptable excipients. The active ingredient includes indigo naturalis, indigo, indirubin, or any combination thereof; the microspheres are coated with an enteric outer layer. The controlled-release pharmaceutical composition provided by this invention can alleviate the symptoms of inflammatory bowel diseases, especially ulcerative colitis, and can reduce or avoid the endocytosis of the active ingredient by intestinal macrophages, thereby reducing the impact on the patient's liver. It exhibits good stability, and the controlled-release pharmaceutical composition of this invention reduces side effects while maintaining therapeutic efficacy.

The invention discloses indigowoad root indigo antibacterial solid soap and a preparation method thereof. The indigowoad root indigo antibacterial solid soap is prepared from the following components in parts by mass: 5-30 parts of indigowoad root powder, 1000-1100 parts of soap base and 36-40 parts of coconut oil. The invention relates to the technical field of daily chemicals. According to the indigo indigo antibacterial solid soap and the preparation method thereof, high-purity indigo indigo powder is specially extracted, and a low-temperature cold soap making method is adopted, so that decomposition of indigo indigo and indirubin under high temperature and strong alkali is greatly avoided, and high efficiency of antibacterial and anti-inflammatory biological activity is ensured; impurities in crude indigo naturalis are removed, the risk of skin allergy and friction is reduced, the compounded soap base also makes the soap foam fine and smooth, and the skin is moist and not tight after the soap is used.

The application provides a radix isatidis granule and a preparation method thereof, which is prepared from the following components in parts by weight: radix isatidis 700 parts, sucrose 170-190 parts and dextrin 50-70 parts. The content of active ingredient (R,S)-deoxyschizandrin, the total content of uridine, guanosine and adenosine, and the content of indirubin in the prepared radix isatidis granule are significantly improved, and the quality is stable after being accelerated for 6 months.

The present invention relates to indirubin derivatives with novel heterobicyclic residues and their use as inhibitors of FLT3 (fms-like tyrosine kinase 3; FMS-like tyrosine kinase 3) and rearranged during transfection (RET) kinases. The compounds of the present invention are capable of effectively inhibiting the activity of FLT3 and RET kinases and are useful in the prevention or treatment of mutant FLT3 and mutant RET-associated diseases, in particular acute myeloid leukemia.

The invention discloses an amino acid mutant of flavin-dependent monooxygenase and an application of the amino acid mutant. The amino acid mutant is obtained by modifying an amino acid sequence of the flavin-dependent monooxygenase MeFMO from Methylophaga sp.strain SK1. The amino acid mutant has the advantages that the flavin-dependent monooxygenase MeFMO can be used for preparing the flavin-dependent monooxygenase MeFMO; according to the present invention, the flavin-dependent monooxygenase is subjected to directional modification through the gene engineering technology so as to obtain the mutant strain with the improved indole catalytic activity, the mutant strain is further combined with beta-glucosidase Asbg1 to construct the one-pot reaction system for preparing the indirubin, and the directional preparation of the indirubin is achieved through the optimization of the process reaction conditions.

This invention relates to a method for producing indirubin using a co-culture system of *E. coli*, comprising the following steps: Step 1, culturing a first engineered bacterium to the late logarithmic growth stage to obtain a fermentation broth of the first engineered bacterium; Step 2, activating and culturing a second engineered bacterium to the early logarithmic growth stage, collecting and resuspending the bacterial cells to obtain a bacterial suspension of the second engineered bacterium; Step 3, inoculating the bacterial suspension of the second engineered bacterium into the fermentation broth of the first engineered bacterium, adding cysteine ​​to begin co-culture, and adding an inducer to induce expression; when co-culturing for 16-30 hours, adding indigo and / or 2-hydroxyindole; continuing co-culturing for 40-60 hours to obtain a fermentation broth containing indirubin. This invention, through a staged culture-mixed co-culture strategy, effectively solves key technical bottlenecks such as heavy metabolic burden of single strains, high toxicity of the intermediate product indole, and high production of the byproduct indigo, achieving a shake-flask level yield of 163.34 mg / L of indirubin, demonstrating good prospects for industrial application.

The present invention provides a controlled-release pharmaceutical composition containing Indigo Naturalis or its main active ingredient, and a preparation method and use thereof. The controlled-release pharmaceutical composition includes micropellets. The micropellets include an active ingredient and one or more pharmaceutically acceptable excipients, the active ingredient includes Indigo Naturalis, indigo, indirubin, or any combination thereof; wherein the micropellets have an enteric outer layer. The controlled-release pharmaceutical composition provided by the present invention can alleviate the disease condition of inflammatory bowel disease, especially ulcerative colitis, and can reduce or avoid the phagocytosis of the active ingredient by intestinal macrophages, thereby reducing the effect on the patient's liver. The composition exhibits good stability and reduces side effects while maintaining therapeutic efficacy.

The invention belongs to the technical field of biological medicines, and discloses application of isatin in preparation of a medicine for treating polycystic ovarian syndrome. The medicine for treating the polycystic ovarian syndrome contains isatin or a derivative thereof. The medicine for treating the polycystic ovarian syndrome can be an oral preparation, an injection, a granule, a pill, a capsule, powder, a slow-release or controlled-release preparation, a targeted preparation and other preparations. The preparation method of the medicine for treating the polycystic ovarian syndrome comprises the following steps: S1, purifying isatin, and preparing isatin crystals with the purity greater than 99%; and S2, adding 100 mg of isatin into 10 ml of the 1% sodium carboxymethyl cellulose solution by taking the 1% sodium carboxymethyl cellulose solution as a solvent, and carrying out ultrasonic uniform mixing at 50 DEG C to prepare a 10 mg / ml isatin solution, namely the medicine for treating the polycystic ovarian syndrome. The medicine for treating the polycystic ovarian syndrome is prepared from isatin or the derivative thereof, and reference value is provided for preparing the medicine which is good in effect, small in toxicity and low in side effect.

The invention belongs to the technical field of purification, and particularly provides a biological indigo purification method which comprises the following steps: culturing a biological indigo fermentation product based on an engineering strain for producing indigo modified by synthetic biology; hydrolyzing the biological indigo fermented product with a hydrolysis reagent to obtain a biological indigo precipitate; purifying the biological indigo precipitate in a solvent pulping manner to obtain a biological indigo refined substance; and drying the purified biological indigo refined substance to obtain a high-purity biological indigo and / or indirubin mixture. Based on the purification method provided by the invention, the content of the biological indigo can reach 95.1%, the purity of the indigo is greatly improved, and the method is more suitable for the biological indigo in the fields of foods, cosmetics, medicines and the like.

The invention belongs to the technical field of biological medicines, and particularly relates to application of indirubin in preparation of a medicine for treating polycystic ovarian syndrome. The indirubin disclosed by the invention is a natural product or an artificially synthesized product, is high in safety and small in toxic and side effects, and has a good effect of treating the polycystic ovarian syndrome.

A biosynthetic method and composition for producing indigo dyes comprising indigotin and isatin. A tryptophanase (TRP) and a flavin monooxygenase (FMO) can be produced through a transgenic organism having carrier encoded tryptophanase and flavin monooxygenase. The produced tryptophanase and flavin monooxygenase convert L-tryptophan into indigo dyes in the presence of one or more bioactive additives selected from cysteine, 2-hydroxyindole, or 2-indoxyl, and the weight ratio of indigotin to isatin in the dyes is between 1:0.1 to 1:4. The dyes have a hue of X: 0.1920 to 0.2481, Y: 0.2537 to 0.2019, Z: 0.5543 to 0.5501 in the CIE XYZ color space definition. Selectable and repeatable dyeing hues are provided.

This invention relates to a method for preparing indirubin, comprising the following steps: S1, pretreating indigo leaves containing indoside to prepare an indoside solution; S2, removing carbonyl compounds from the indoside solution obtained in step S1 to obtain indoside; S3, decomposing the indoside obtained in step S2 to obtain a solid mixture of indirubin and indigo; S4, separating the solid mixture of indirubin and indigo obtained in step S3 to obtain indigo and indirubin. Compared with the prior art, this invention improves the conversion rate of indirubin and reduces the conversion rate of indigo by removing carbonyl compounds to change the oxidation properties in the reaction system, thereby increasing the formation of the intermediate product indirubin and achieving a high-yield preparation of plant indirubin. It has the advantages of simple process, low cost, and high directional conversion efficiency of indirubin.

The invention discloses a quality detection method of a strobilanthes cusia medicine. The detection method comprises the following steps: determining the content of water, total ash content, acid-insoluble ash content and extract in the strobilanthes cusia medicinal material; and performing thin-layer identification on stems and leaves of the strobilanthes cusia medicinal material. The thin-layer chromatography identification method established by the invention can simultaneously identify the thin-layer chromatography of indirubin, indigo blue and indoleglycoside, has clear and visible spots and no obvious tailing phenomenon, can better reflect the medicinal material components of the strobilanthes cusia, and can qualitatively identify the strobilanthes cusia medicinal material. And a research basis is provided for quality standard research of the strobilanthes cusia medicinal material and development of preparation products.

The present application relates to a method for preparing indirubin, comprising the steps of: forming a primary culture medium by primarily culturing an enzyme and Escherichia coli so that the enzyme is expressed in the Escherichia coli; adding isatin to the primary culture medium so as to form a secondary culture medium; secondarily culturing the secondary culture medium so as to form a tertiary culture medium; and mixing the tertiary culture medium and a solvent and performing separation so as to extract indirubin, wherein the isatin is converted into indirubin by using the Escherichia coli and the enzyme.

The invention discloses a traditional Chinese medicine compound multi-layer coated microsphere preparation for treating pancreatic cancer and a preparation method thereof. The preparation is prepared from the following active components in parts by weight: 10-35 parts of astragalus extract, 8-25 parts of ganoderma lucidum spore powder, 5-18 parts of sculellaria barbata general flavone and the like. The preparation method comprises the following steps: a) directionally extracting active ingredients; b) removing toxic substances from the dried toad skin through molecular imprinting; c) constructing three layers of coated microspheres, wherein a core layer is a nanocrystal (indirubin / chelidonine / toad peptide), a middle layer is a phospholipid complex (flavone / polysaccharide), and an outer layer is a pH response polysaccharide microsphere; and d) pressing to obtain the three-layer sustained-release tablet. The preparation realizes colon-targeted drug release, the bioavailability is obviously improved, the tumor inhibition rate of animal experiments is improved, and the chemotherapy drug resistance can be reversed.

The invention discloses a composition, a pharmaceutical preparation and application thereof. Based on a stress-induced alopecia resting model, it is proved for the first time that the main component trans-stilbene glucoside (TSG) of polygonum multiflorum and the main components indirubin and indigo blue of indigo naturalis have a remarkable drug effect on stress-induced alopecia resting model mice, and the components are easy to extract and have high safety. A stable and reliable animal model and an evaluation method are provided for treatment strategies and new drug research and development of stress-induced alopecia in the resting period.

Compositions comprising an AhR agonist compound, such as indigo and / or an indigo derivative, such as indirubin and isatin, are described. Methods of treatment, including the treatment of ulcerative colitis, by administering the compositions are described. In an embodiment, compositions in the form of a solid amorphous dispersion of the AhR agonist are described.

The invention belongs to the technical field of biological medicines, and discloses application of isatin in preparation of a medicine for treating hyperandrogenemia. The medicine for treating the hyperandrogenemia contains isatin or a derivative thereof. The medicine for treating the hyperandrogenemia has the following preparation forms: an oral preparation, an injection, a granule, a pill, a capsule, powder, a slow-release or controlled-release preparation, a targeted preparation and preparations of other administration routes. The preparation method of the medicine for treating hyperandrogenemia comprises the following steps: S1, purifying isatin to obtain isatin crystals with the purity of more than 99%; s2, taking 0.5% tragacanth solution as a solvent, adding 100mg of isatin into 10ml of 0.5% tragacanth solvent, and magnetically stirring at 37 DEG C to prepare 1mg / ml of isatin solution. According to the invention, the isatin or the derivative thereof is used for preparing the medicine for treating hyperandrogenemia, so that reference value is provided for preparing the medicine with good effect, low toxicity and low side effect.

The present invention relates to the field of pharmaceutical technology, and specifically discloses a drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and resolving macules, and a preparation method thereof. The drug is composed of indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and licorice; the preparation method includes mixing agrimonia pilosa and cortex moutan and extracting with alcohol to obtain extract 1; soaking forsythia suspensa in water, extracting volatile oil by steam distillation method, storing the volatile oil, and collecting the medicinal residues and decoction 1 of forsythia suspensa; mixing the medicinal residues of forsythia suspensa and licorice and decocting with water to obtain a decoction, mixing with decoction 1, and concentrating to obtain extract 2; combining extract 1 and extract 2, drying, pulverizing, adding fine powder of indigo naturalis and dextrin, granulating, sizing, and then adding the volatile oil of forsythia suspensa and mixing evenly to obtain the product. The drug of the present invention can reduce the flying dust in production during preparation, is friendly to the production environment; the drug can improve the content uniformity of indirubin in indigo naturalis, meets the production standards of the pharmacopoeia, meets the production requirements of the industry, and is suitable for large-scale production.

The invention relates to the technical field of biological medicines, in particular to application of indirubin in preparation of a medicine for treating oligoasthenospermia. The indirubin disclosed by the invention is a natural product or an artificially synthesized product, is high in safety and small in toxic and side effects, and has a good effect of treating oligoasthenospermia.

There is provided pharmaceutical compositions comprising disulfiram (DSF) or copper di-ethyldithiocarbamate (CuET), an indirubin compound such as 6-bromo-indirubin-3'-oxime (BIO), and a stabilizer, wherein the disulfiram or CuET, the indirubin compound, and the stabilizer are associated with a lipid nanoparticle. The pharmaceutical compositions are particularly suitable for treating a cancer overexpressing p97 and NPLOC4.

A biosynthetic method and composition for producing an Indigo dyestuff including Indigotin and Indirubin. Tryptophanase (TRP) and flavin-containing monooxygenase (FMO) are generated from a genetically-modified organism having a vector coding for tryptophanase and flavin-containing monooxygenase. The conversion of L-tryptophan to Indigo dyestuff is converted by the generated TRP and FMO in the presence of one or more bioactive additives selected from the cysteine, 2-oxindole, or 2-indoxyl to form a dyestuff having a ratio of Indigotin to Indirubin by weight between 1:0.1 to 1:4. The dyestuff has a color hue defined by CIE XYZ color space with X: 0.1920 to 0.2481, Y: 0.2537 to 0.2019, Z: 0.5543 to 0.5501. Selectable and reproduceable color hues are provided.

The present invention relates to compounds, compositions, and methods for modulating skin pigmentation and treating or preventing UV-induced skin damage, erythema, aging of the skin, sunburn, and hyperpigmentation in a subject. The compounds, compositions, and methods of the present invention generally involve Malassezia-derived compounds, including malassezin and indirubin, and / or chemical analogs thereof. Other applications of the compounds and compositions disclosed herein include, but are not limited to, improving hyperpigmentation caused by a hyperpigmentation disorder, inducing melanocyte apoptosis, and modulating arylhydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogenesis, melanosome transfer, melanocyte activity, and melanin concentration.

The invention provides an enema nano suspension system for treating ulcerative colitis, which is prepared by taking indigo blue and indirubin as active components, adding a space stabilizer and a potential stabilizer and adopting a wet medium grinding method. The invention also provides an enema nano-foam system for treating ulcerative colitis. The enema nano-foam system comprises the drug-containing foam base liquid and the propellant. Aiming at the problems of poor solubility and permeability of indigo blue and indirubin, auxiliary materials are combined with a ball milling technology, and indigo blue and indirubin are subjected to surface modification and nanocrystallization, so that the solubility and permeability of indigo blue and indirubin are improved, the absorption of inflammatory cells to drugs is enhanced, and the bioavailability of indigo blue and indirubin is improved. The problems that conventional dosage forms such as traditional Chinese medicine rectal administration enema liquid and suppositories are prone to leakage, strong in foreign body sensation, limited in medicine distribution area and difficult to reach deeper ulcer lesions in intestines are solved, and the vacancy that at present, no convenient and effective enema treatment is available for ulcerative colitis is made up.