117 results about "Cinobufagin" patented technology

The invention discloses a total bufogenin extract with antitumor function and also discloses a preparation method of the extract and application thereof in the preparation of antitumor medicines. The total bufogenin extract of the invention is prepared by organic solvent extraction, column chromatography separation and purification of dried toadskin; the content of total bufogenin is over 80 percent, wherein the content of resibufogenin is over 12 percent, the content of cinobufagin is over 4 percent, and the content of bufotalin is over 10 percent. Compared with the prior art, the invention eliminates bufotenine alkaloid which has irritation, is easy to cause hypersensitivity but has no antitumor activity, efficiently collects the effective part of total bufogenin which has significant antitumor activity, therefore pharmacological action is stronger, the clinical curative effect is higher and the toxic and side effect is lower. The total bufogenin extract can be prepared into various pharmaceutical preparations for clinical application, therefore the invention has the functions of killing tumor cells, inducing differentiation and apoptosis of tumor cells, inhibiting the neovascularization of tumor cells and lowering the neoplasm metastasis rate, etc.

The invention provides a bufadienolides extraction extracted from the toad skin or the toad venom; wherein, the weight percentage of the bufadienolides (accounted by the cinobufagin) can reach above 55%. The invention adopts the extraction method that: the toad venom, the toad skin or the bufo siccus is extracted by the ethanol; after the recovery of the ethanol, the macroporous resin column on the concentration liquid is eluted by the water and the low concentration alcohol, and is eluted by the high concentration alcohol, then the final product is gained through collecting the eluent and reducing the pressure of the recovery solvent to pass drying or extraction. The invention has an advantage that: the invention also provides the drug composition using the extraction as the active component, the suppressing the tumour cells active function of the extraction and the application in the preparation of the anti-tumor drug.

The invention discloses an extraction method of a land slug and an anti-lung cancer application of the land slug. The extraction method comprises the following steps: (1) carrying out vacuum freeze-drying on the land slug, adding purified water and then carrying out water bath agitation, adding a high-concentration ethanol solution, evenly agitating until the ethanol concentration is 60-70%, standing and then carrying out solid-liquid separation; (2) clarifying and intercepting the liquid obtained in the step (1) by adopting an inorganic ceramic membrane system, so as to obtain total clear liquid of the land slug; (3) concentrating the total clear liquid of the land slug obtained in the step (2) by a reverse osmosis membrane; and (4) concentrating and drying ultra-filtrate obtained in the step (3), so as to obtain water-soluble land slug powder. The molecular weight of the land slug powder obtained by the method is concentrated between 20,000 and 30,000, and has a significant antitumor effect; the tumor control rate is higher than that of cinobufagin and close to that of cyclophosphamide. The water-soluble land slug powder disclosed by the invention is used for treating a lung cancer, and is efficient and low-toxicity.

The invention provides a medicinal composition of Cinobufacini, which is prepared into the forms of drop pill, or dispersible tablet, or soft capsule, or effervescent tablet, or orally disintegrating tablet, or mini-pill, or suppository. The invention also discloses their preparing process. The composition comprises dried toad skin extract and Job's-tears seed oily extract by the weight ratio of 1:0.05-30.

The invention discloses a process for preparing Cinobufacini freeze dried injection, which is prepared from indole alkaloid significant part extracted from dried toad peels and medicinal adjuvant through freeze drying, the Cinobufacini significant part is prepared through warm water extraction, centrifuging, and ultrafiltration purification.

The invention discloses a heart-protecting musk oral preparation and a preparation method thereof. The invention is characterized in that musk, artificial cow-bezoar, Chinese cinnamon, storax and toad venom are extracted to obtain an extract, the extract is mixed with a ginseng extract and borneol, and medical auxiliary materials are added to be prepared into an oral preparation; the toad venom is controlled at 2-4 mu g / bottle according to the total amount of the bufogenin and the cinobufagin; and the pharmacological tests show that each group of the preparations has good action of curing the heart disease and especially has the action of promoting the angiogenesis of the heart.

The present invention provides preparation process of toad skin total alkaloid. The toad skin total alkaloid contains indole total alkaloid 50-95 wt%, cinobufagin and lipo bufogenin 0.02-0.08 wt%, and toad thetine 20-50 wt%. The present invention provides also the method of measuring toad thetine content, and the injection, powder for injection, dripping pill, capsule, oral liquid, etc with the oad skin total alkaloid as effective component and their preparation process.

A freeze-dried powder injection of cinobufotoxin is prepared from the aquatic extract of dried toad skin and the pharmacologically acceptable carrier. Its preparing process and its quality control method are also disclosed. Its advantages are high curative effect and low poison.

The invention relates to a traditional Chinese medicine venenum bufonis extract. A method for extracting the extract includes steps of extracting traditional Chinese venenum bufonis medical materials at the temperature ranging from 60 DEG C to 90 DEG C by ethanol water with volume percent of 60-95% in a backflow manner, separating extract liquid via silicagel columns after the extract liquid is concentrated, adopting petroleum ether and acetone with volume ratio of 1-8:1 as eluant to realize gradient elution, collecting parts of eluent, and filtering, concentrating and drying the eluent in a pressure reduction manner to obtain the traditional Chinese medicine vanenum bufonis extract containing mixture of three types of bufotalin including resibufogenin, cinobufagin and bufalin, wherein the sum of the weight percentages (calculated when three types of the bufotalin are dried) of the three types of the bufotalin is higher than or equal to 95%. The invention further provides the preparation method for the traditional Chinese medicine venenum bufonis extract. The sum of the weight percentages of the three types of the bufotalin in the traditional Chinese medicine venenum bufonis extract is higher than 95%, extraction transfer rate is high, the quantity of used solvent is lower, residual solvent is little, pollution degree is lower, operation is simple and convenient, and industrial production is realized easily.

The invention provides a method for measuring the contents of indole alkaloids in cinobufagin alcohol precipitation liquid. The alcohol precipitation method is a key unit operation in the production process of cinobufagin injection and a quick and effective content analysis method aiming at the alcohol precipitation process is especially important. The method comprises the following steps of: collecting a representative alcohol precipitation liquid sample as a correction set; measuring the contents of the indole alkaloids by adopting ultraviolet visible spectrophotometry and scanning a near-infrared original spectrum chart of the bisindole alkaloids at the same time; selecting a proper spectrum preprocessing method, a modeling spectrum section and a main factor number; and constructing a near-infrared quantitative correction model of the indole alkaloid of the alcohol precipitation liquid sample and quickly measuring the content of the cinobufagin alcohol precipitation liquid sample with the unknown content by using a chemometric method. The invention has the advantages of quickness, no damage and accuracy, can effectively solve the problems of lacking of quality monitoring and batch difference in the alcohol precipitation process and provides a new idea and means for quality control of the traditional Chinese medicine process.

The invention discloses a Chinese toad bufotoxin extract and a preparation method thereof. The extract contains the main effective components of cinobufagin with the content more than 0.15 percent and resibufogenin with the content more than 0.10 percent. The extract is made from dry toad skin and is prepared by the technologies of poaching, column chromatographic separation, eluting, condensing, drying, etc. The invention effectively removes useless substances (impurity) in the extract, is enriched in effective component and achieves the goals of improving the curative effect and reducing the toxic and side effects.

The invention provides application of gamabufotalin and a salt compound thereof in preparation of a medicine for treating gynecological tumor. By comparing in vitro anti-cancer experiments of a bufadienolide extract and monomeric compounds, namely the gamabufotalin, cinobufagin, bufalin and bufotalin as well as hydrochlorides or sulfates of the four compounds to four gynecological tumors, namely human ovarian cancer cells A2780, human ovarian cancer cells SK-OV-3, human cervical carcinoma cells and human endometrial cancer cells, an experimental result shows that the gamabufotalin has stronger activity against gynecological tumor cells than the bufadienolide extract and the monomeric compounds, namely the cinobufagin, the bufalin and the bufotalin, and the hydrochloride or the sulfate of the gamabufotalin has stronger activity against gynecological tumor cells than the hydrochlorides or the sulfates of three compounds, namely the cinobufagin, the bufalin and the bufotalin. The gamabufotalin and the salt compound thereof provided by the invention have the advantages of clear components, controllable quality, strong anti-cancer activity, and small adverse reaction, and are expect to be developed into a novel anti-cancer drug.

The invention relates to a traditional Chinese medicine toad venom dissimlar extract and a preparation method thereof, and belongs to the technical field of drugs. The preparation method of the extract comprises the steps of crushing toad venom medicinal materials into middle power, and adding 4 to 10 times of water for grinding and dispersing; adding ethyl alcohol to carry out alcohol precipitation, and storing at a low temperature; adding sodium chloride into supernatant liquor for salting out at a low temperature; carrying out concentration under reduced pressure until block-shaped toad venom dissimlar extract is separated out, carrying out drying or concentration under reduced pressure until nearly dry, carrying out vacuum drying, and adding ethanol recrystallization, so as to obtain the toad venom dissimlar extract containing resibufogenin, cinobufagin venom toad and bufalin; the transfer rate of the mixture of three bufogenins is about 80%, and the sum of weight percentages of the three bufogenins is equal to or greater than 35%. The toad venom extracted by adopting the method has the advantages of high transfer rate and active ingredient content, no residual organic solvent, simple and convenient operation, low energy consumption, and easiness in controlling of product quality, and is suitable for industrializing production.

The present invention relates to medicine technology, and is nanometer granular cinobufagin-albumin preparation as one new preparation form of cinobufagin and its preparation process. Cinobufagin has high antitumor effect but high toxicity and short intracorporeal half life. The nanometer granular cinobufagin-albumin preparation of the present invention has round shape of nanometer grains, narrow grain size distribution in the range of 50-250 nm, average grain size of 125.9 nm, liver targeting and delayed releasing, so that it has raised curative effect and lowered toxicity and may be used in preparing medicine for treating liver cancer.

The invention relates to a cinobufagin dry power inhaler, in particular to a dry power inhaler made of cinobufagin, a preparation method of the dry power inhaler and application of the dry power inhaler in preparation of drugs for treating tumors of lung. The cinobufagin dry power inhaler is characterized by consisting of the cinobufagin and medically acceptable auxiliary materials, and the mass ratio of the cinobufagin to the medically acceptable auxiliary materials is 1: 0.03 - 1:110. The cinobufagin is prepared to be the dry powder inhaler, therefore, the cinobufagin can be directly acted on pulmonary lesions, the happening of adverse actions is reduced, the bioavailability of the drug is enhanced, the defects of oral formulation including slow effect, liver first-pass effect to liver,low bioavailability and the like are overcome, and synchronously the problems of injection including inconvenience for use, bad compliance of patients and the like are also solved.

The present invention discloses the application of toad venom extract containing more than 90% of bufolin, cinobufagin and cinobufagin in the preparation of medicines for treating human glioma. The content ratio of tobafagenin is 2:3:5, and the extract of toad venom is prepared into a nano-preparation. The bufagenin nano-preparation of the invention can increase the distribution of bufagenin in the brain and avoid being taken up by the heart, thereby improving the brain-targeting property of the drug and reducing cardiotoxicity. Compared with the common extract solution of bufogenin, the nano-preparation of bufogenin has a stronger therapeutic effect on glioma brain and less side effects, thus enhancing the use value of bufogenin and providing a new method for the treatment of glioma. new drug.

The invention relates to the technical field of Chinese traditional medicine preparation, in particular to cinobufagin injection effective component and new use of the effective component in preparation of antineoplastic drug. The invention uses macroporous absorbent resin to separate effective components from cinobufagin injection; water and 50% ethanol are then respectively to use for eluting components of various polarities separated by HP-20 macroporous absorbent resin; the components are then analyzed and distinguished by thin layer chromatography and high performance liquid chromatography to prepare non-polarity components of cinobufagin injection with lipophilic phrynin lactone substances and polarity components of water-soluble alkaloid substances. In vivo and in vitro anti-tumor tests of the cinobufagin injection effective component has proven that the cinobufagin injection effective component can inhibit SW1990 auxesis; the cinobufagin injection effective component has obvious inhibiting effect to tumor growth of nude mice loaded with human pancreatic cancer which can be used for further preparation of anti-human pancreatic cancer drug, in particular for preparation of anti-human pancreatic cancer drug which comprises non-polarity components of cinobufagin injection.

The invention relates to the technical field of traditional Chinese medicines and in particular discloses venenum bufonis extract with anti-infection action and a preparation method thereof. The venenum bufonis extract contains a phrynin effective component which contains the following components in parts by weight: 30-60 parts of arenobufagin, 35-60 parts of cinobufagin, 10-25 parts of telocinobufagin, 20-45 parts of bufotaline, 20-50 parts of cinobufotalin, 25-45 parts of bufalin, 15-40 parts of resibufogenin and 5-15 parts of hellebrigenin. The venenum bufonis extract provided by the invention is remarkable in anti-infection effect. In addition, the types and content of effective components of the extract are clear, the cytotoxicity is small, and quality control and medicinal safety of the extract are facilitated.

The invention relates to a bufogenin compound and an application thereof in preparing anti-tumor medicaments. The bufogenin compound comprises cinobufagin and derivatives thereof, contains pharmaceutically acceptable salts thereof, has a chemical structural formula which is shown in the specification, wherein groups R1, R2, R3 and R4 are respectively selected from hydrogen, halogens, C1-C6straight chain or branch chain saturated or unsaturated alkyls, C3-C7 ring alkyls, benzyls, aromatic groups or 5-7-tuple heterocyclic groups. Proved by in-vitro cellular experiments, the compound can remarkably inhibit the proliferation of liver cancer and lung cancer cells and accordingly can be used for preparing medicaments for inhibiting tumor growth.

The invention provides application of a bufadienolide compound and a bufadienolide salt compound in preparing a medicine for treating gynecological tumor. Anti-cancer experiments of four gynecological tumor, namely human ovarian cancer cells (A2780), human ovarian cancer cells (SK-OV-3), human cervical carcinoma cells (SiHa) and human endometrial cancer cells (shikawa) are carried out in vitro through a bufadienolide extract and monomeric compounds, namely cinobufagin, bufalin, bufotalin and gamabufotalin as well as hydrochlorides or sulfates of the four monomeric compounds, and an experimental result shows that the bufadienolide extract, the monomeric compounds, namely the cinobufagin, the bufalin, the bufotalin and the gamabufotalin, and the hydrochlorides or the sulfates of the four monomeric compounds have strong inhibition effect on four gynecological tumor cells. The anti-cancer activity of the bufadienolide compound and the bufadienolide salt compound is stronger than that of a positive drug paclitaxel, and the bufadienolide compound and a bufadienolide salt compound have small adverse reaction and expect to be developed into a novel anti-cancer drug.

The invention discloses a method for detecting compounds in a toad venom. The method for detecting the compounds in the toad venom comprises the steps of the preparation of a reference solution, the preparation of a test solution, determination of chromatographic conditions, determination of relative correction factor, determination of component content of the test solution, and the like. Cinobufagin is selected as an internal standard substance. The method for detecting the compounds in the toad venom not only solves a problem that a reference product is expensive and rare, but also complieswith a principle of environmentally friendly and green Chinese medicine, and the cinobufagin with high content, stable peak shape and low price is selected as the internal standard substance. At the same time, the content of six compounds in the toad venom is measured, the detection efficiency is greatly improved and the quality of the toad venom is comprehensively controlled. According to a detection object to determine a reasonable mobile phase, a chromatographic column, an elution procedure, a detection wavelength, a column temperature and other chromatographic conditions, under the selected chromatographic conditions, the content of the compounds in the toad venom can be quickly determined, precision is high, reproducibility is good, stability is good, recovery rate is high and measurement results are accurate .

The invention provides medicine containing toad venom lipid-soluble substances and a preparation method thereof. According to the toad venom lipid-soluble substances, the weight sum of bufalin, cinobufagin and resibufogenin is larger than 50% of the total weight of the toad venom lipid-soluble substances. The preparation method of the toad venom lipid-soluble substances includes the steps that toad venom herbs are smashed, then absolute ethyl alcohol is added, the amount of the absolute ethyl alcohol is 5-50 times that of the herbs, heating reflux is performed on the mixture for 1 h in a water bath of 60 DEG C, then the mixture is cooled to indoor temperature, suction filtration is performed, dry extract is obtained after filtrate is evaporated to dryness, purified water is added into the extract for ultrasonic suspending, the amount of the purified water is 5-30 times that of the extract, and extracting is performed through chloroform, wherein the amount of chloroform is 5-50 times that of the mixture. The invention further provides a medicine composite and a preparation method thereof. The medicine composite is a toad venom extract lipid microsphere oral solution and is used for treating gastrointestinal tumors.

The invention discloses a use of a bufadienolide compound in preparing medicines for treating oral mucosal malignant tumors. Anti-cancer experiments of human tongue squamous cancer cells are carried out in vitro through a bufadienolide extract and monomeric compounds, namely gamabufalin, arenobufagin, telocinobufagin, bufotaline, cinobufagin, desacetylcinobufotalin, heloniogenin, resibufogenin, and cinobufotalin, and experimental results show that the bufadienolide compound has strong inhibition effect on tongue squamous cancer cells and compared with the bufadienolide extract and eight monomeric compounds, namely gamabufalin, arenobufagin, telocinobufagin, bufotaline, desacetylcinobufotalin, heloniogenin, resibufogenin, and cinobufotalin, cinobufagin has a stronger anti-tumor cell activity. The bufadienolide compound provided by the invention has clear components, controllable quality, strong anti-tumor activity and little adverse reaction and is expected to be developed into a novel anti oral mucosal malignant tumor medicine.

The invention discloses a plaster paster for treating femoral head necrosis and pains in the neck, shoulder, lumbar and legs. The plaster paster is prepared from ginseng, cornua cervi pantotrichum, herbal ephedrae, fossilized, bombyx batryticatus, cinobufagin venom toad, rhizoma seu radix notopterygii, dienagkistrodon acutus, rhizoma dioscoreae nipponicae, syngnathussp, cinnamon, nux vomica, arisaema heterophyllum blume, olibanum, myrrh, leech, buthus martensi kirsch, radix aconiti carmichaeli, radix aconiti, radix aconiti agrestis, dragon's blood, manis pentadactyla, asarum sieboldi mig., radix notoginseng, momordica cochinchinensis, ferula asafetida, angelica sinensis, radix achyranthis bidentatae, the rhizome of davallia, radix polygoni multiflori, corydalis amabilis, radix paeoniae alba, notopterygium incisum, carthamus tinctorius L., ramulus cinnamomi, curcuma zedoary, lumbricus, rehmannia glutinosa, radix angelicae pubescentis, herba epimedii, berba aristolochiae mollissimae, eucommia ulmoides, centipede, radix saposhnikoviae, radix clematidis, Chinese polyphaga, fructus psoraleae, rhizoma dioscoreae nipponicae, Chinese blister beetle, camphor, borneol, and rhizoma corydalis. The formula is rigid, the plaster paster is manufactured through a traditional method for preparing plaster pasters, the effective components of all medicines are reserved to the greatest extent, and the diseases of femoral head necrosis and the pains in the neck, shoulder, lumbar and legs can be effectively cured once and for all.

The invention discloses single-dosage package arenobufagin. The single-dosage package arenobufagin is characterized in that white slurry of ear-side glands and dermal gland of bufo bufo gargarigans or bufo melanostictus is taken to be screened to remove impurities and to be dried at low temperature, and smashing is conducted to obtain arenobufagin powder. Single-dosage package is conducted according to the adult single dosage of the total amount, being 0.08-10 mg, of cinobufagin and resibufogenin, and the package difference limit is smaller than or equal to + / -15% according to the net weight, being 1-100 mg, of arenobufagin in the single-dosage package. The small-package arenobufagin is suitable for traditional Chinese medicine decoctions, pills and powder and suitable for external application. By means of the low-temperature drying, particularly freezing drying technology, active components of arenobufagin are kept to the maximum extent; by strictly controlling the total amount of cinobufagin and resibufogenin in the single-dosage package, the use safety problem of arenobufagin is effectively solved, and the last barrier is broken for clinical application of arenobufagin.

The invention discloses a high purity bufonis veneum direct oral decoction piece and a preparation method thereof. The bufonis veneum direct oral decoction piece is in single dose package with a specification of 1-60mg, and the bufonis veneum powder particle size is smaller than or equal to 50 meshes. Calculated on a dry product, the total amount of bufalin, cinobufagin and resibufogenin contained in the direct oral decoction piece is not less than 6.5% (g / g), the total ash is not more than 5.0%, and the acid-insoluble ash does not exceed 2.0%. Salmonella (10g) is not detected in the product, and bile salt resistant gram-negative bacteria is less than 10000cfu (1g). The bufonis veneum direct oral decoction piece is produced in workshops conforming to the "good manufacture practice of drugs". The preparation method includes: (1) raw material inspection; (2) primary crushing; (3) processing with wine; (4) filtering; (5) drying; (6) second crushing; (7) inner packing; (8) outer packaging; and (9) finished product inspection. Specifically, the steps (2)-(7) are carried out in a D grade clean production area, and the step (8) is conducted in a general production area. The bufonis veneum direct oral decoction piece is in single dose package, has the advantages of accurate dosage, controllable production process, good safety, and qualified microbial limit, the product is in accordance with the quality standards of direct oral drugs, and is suitable for direct oral taking.

The invention relates to a novel use of cinobufagin and resibufogenin and concretely relates to a use of cinobufagin and resibufogenin in preparation of drugs for preventing and treating the hand-foot-and-mouth disease and especially in preparation of drugs for resisting enterovirus type 71.

The invention relates to application of a medicine composition in preparation of medicine for preventing and treating unstable angina. The composition is prepared from the following ingredients including radix ginseng, radix aconiti lateralis praeparata, glossy ganoderma, flos carthami, musk, bear gall, pearl, cinobufagin venom toad, borneol and bezoar. The composition can obviously improve the rabbit blood fat level of an unstable angina model; the inflammatory factor release is reduced; the myocardial damage can be reduced; a good curative effect can also be realized on patients with the unstable angina.

The invention provides novel application of cinobufagin in preparation of medicine for treating pulmonary fibrosis. According to the application, the cinobufagin has an excellent effect on pulmonary fibrosis without adverse response, can be used for retarding pulmonary fibrosis of a mouse induced by bleomycin, and provides an excellent application prospect for treating, relieving or improving pulmonary fibrosis diseases.

Through a method of MTT, the individual effects of cinobufagin and the influence of combined effects of the cinobufagin and canavaline A or lipopolysaccharide on the reproduction or conversion of splenic lymphocytes of a normal mouse are detected; through the method of MTT and neutral red phagocytosis experiment, the influence of CBG on the energy metabolism level and the phagocytosis function of macrophages in the abdominal cavity is detected; through flow cytometry, the influence of the CBG on the splenic lymphocytes period of the normal mouse and the expression of the surface antigens CD4 and CD8 of the T lymphocyte in the spleen is detected. The invention validates that the cinobufagin has the effect of enhancing the immunity.