513 results about "Paclitaxel" patented technology

The invention relates to the field of natural products, in particular to a dimer compound of guaiane type sesquiterpenes and uric acid as well as an extraction and separation method and application of the dimer compound. According to the invention, a new dimer compound of guaiane type sesquiterpene and uric acid is extracted and separated from carpesium abrotanoides in Guizhou, and it is found that the dimer compound has relatively strong anti-tumor activity. The compound has strong inhibitory activity on breast cancer, prostate cancer, nasopharynx cancer, liver cancer, lung cancer, leukemia, pancreatic cancer, glioma, osteosarcoma, skin cancer, cervical cancer, ovarian cancer, kidney cancer and esophageal cancer, and provides an optional scheme for broad-spectrum anti-cancer drugs. Moreover, in human prostate cancer cells PC3, human cervical cancer cells Hela, human liver cancer cells HepG2 and human glioma cells U87 which are resistant to paclitaxel, the compound also shows strong anti-cancer activity, which indicates that the compound has the potential of treating patients resistant to paclitaxel.

Methods of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject, methods of treating chronic rhinosinusitis (CRS) or chronic rhinosinusitis with nasal polyps (CRSwNP) in a human subject, methods of treating a eustachian tube disorder in a human subject, and devices and systems for performing the methods. A method of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject includes inserting a drug-coated balloon catheter into a target site in a trachea, mainstem bronchus, bronchus intermedius, lobar bronchus, segmental bronchus, or sub-segmental bronchus, wherein the balloon is coated with a coating layer including the therapeutic agent and one or more additives. The therapeutic agent includes paclitaxel, sirolimus, or a derivative thereof. The method includes inflating the balloon to dilate the airway and deliver a therapeutic agent to the airway wall. The method includes deflating the balloon. The method also includes withdrawing the balloon catheter from the target site.

The invention relates to the technical field of biological medicine, and discloses a pharmaceutical composition of paclitaxel dimer prodrug nanoparticles and a traditional Chinese medicine compound and application of the pharmaceutical composition, and the pharmaceutical composition is composed of Qiyuansanlong prescription freeze-dried powder and paclitaxel dimer prodrug nanoparticles; wherein the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) or GSH (glutathione) response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs), and the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) and GSH response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs). According to the pharmaceutical composition disclosed by the invention, a traditional Chinese and western medicine synergistic treatment system is innovatively constructed, and the advantage of multi-dimensional synergistic interaction is shown. Firstly, an NQO1 / GSH double-response type intelligent release system is adopted, and a biomarker highly expressed by tumor tissue can be specifically responded to realize precise drug release, so that the PTX concentration in tumors is improved compared with that of a traditional dosage form, and meanwhile, the drug circulation time is prolonged. Secondly, the active ingredients in the Qiyuansanlong prescription freeze-dried powder can significantly down-regulate the PD-L1 expression level, synergistically enhance CD4 + T and CD8 + T cell infiltration, and form chemical-immune dual killing effects.

The invention relates to paclitaxel ganoderma lucidum spore oil self-nanoemulsion composite particles with ganoderma lucidum spores as a carrier and a preparation method of the paclitaxel ganoderma lucidum spore oil self-nanoemulsion composite particles, and belongs to the technical field of medicines. Pretreated Ganoderma lucidum spores (GLS) are obtained through process screening and serve as a drug carrier, and paclitaxel-loaded Ganoderma lucidum spore oil self-nanoemulsion (PGS) is loaded into the Ganoderma lucidum spores (GLS) to obtain paclitaxel-loaded composite particles (PGS (at) GLS). An in-vitro release curve shows that the PGS-atGLS has the characteristic of slow release after reaching the intestinal tract; in-vivo pharmacodynamic experiments show that PGS-atGLS can significantly inhibit development and metastasis of mouse colorectal cancer; tumor tissue slice immunofluorescence analysis shows that PGS-atGLS can effectively play a role in treating colon cancer. The paclitaxel self-nanoemulsion-loaded ganoderma lucidum spore composite particles synergistically promote cancer immune circulation by inducing immunogen cell death and immunoregulation, significantly improve the treatment effect of colon cancer, and have good biological safety.

The invention discloses an OTX-015 (Ox-015) loaded cascaded responsive nano particle and a preparation method thereof. The nanoparticle has a three-layer core-shell structure, wherein the innermost layer is a cross-linked nanoparticle of chitosan and paclitaxel; the middle layer is a polydopamine layer loaded with a bromodomain inhibitor OTX-015; the outermost layer is a gelatin layer grafted with babali; wherein the cross-linked substance of the chitosan and the paclitaxel is a cross-linked substance containing a disulfide bond. The invention also provides a preparation method of the cascade responsive nano-particle and application of the cascade responsive nano-particle in preparation of an antitumor drug targeted delivery system. The nanoparticle provided by the invention improves the tumor microenvironment while activating in-vivo autoimmunity, and kills tumor cells by using photothermal therapy assisted chemotherapy drugs, so that the synergistic effect of chemotherapy / photothermal therapy / immunotherapy is realized, and a new idea is provided for clinical tumor treatment.

The present invention provides an enhanced NK cell, its preparation method and application, belonging to the field of biomedical technology. The present invention uses a compound of quercetin, paclitaxel and resveratrol as a culture medium induction additive to pre-treat NK cells, successfully enhancing the killing toxicity of NK cells against human lung cancer cells and effectively inhibiting tumor growth, opening up a new way for the treatment of lung cancer and having important research value and potential clinical application prospects in the field of tumor immunotherapy.

The invention discloses an SERS (Surface Enhanced Raman Scattering) detection method for paclitaxel drug concentration in blood of a breast cancer patient, and belongs to the technical field of detection. The method comprises the following steps: performing acetonitrile two-step precipitation centrifugal treatment on a blood sample to obtain a detection sample; the method comprises the following steps: constructing a high-sensitivity SERS substrate (the volume ratio of gold nanoparticles to ethanol is 1: (90-100), and a film is formed on a water-cyclohexane interface) through self-assembly of gold nanoparticles on a liquid-liquid interface; the method comprises the following steps: dropwise adding a sample into a substrate, and detecting characteristic peaks of 1024cm <-1 > and 1053cm <-1 > by using a portable Raman spectrometer (785nm, 30mW, 0.5 s); and calculating the paclitaxel concentration in combination with a pre-established quantitative curve. The method is easy and convenient to operate and suitable for clinical bedside rapid monitoring.

The invention discloses a compound liposome, a freeze-dried powder injection as well as a preparation method and application of the freeze-dried powder injection. The compound lipidosome comprises a lipidosome membrane and an inner water phase encapsulated in the lipidosome membrane, the paclitaxel palmitate is encapsulated in a lipid bilayer of the liposome membrane; the gemcitabine or the salt thereof is encapsulated in the inner water phase; the compound liposome comprises the following raw materials: paclitaxel palmitate, lecithin, a polyethylene glycol derivative, gemcitabine or a salt thereof, an organic solvent and a buffer solution A; the molar ratio of the lecithin to the polyethylene glycol derivative is 1: (0.01-0.15). The compound liposome disclosed by the invention is relatively high in encapsulation efficiency (especially the encapsulation efficiency of PTX-PA is relatively good) and relatively high in safety, the preparation method is simple and easy to operate, the industrialization degree is high, and the prepared compound liposome has a relatively good long-circulation effect, a relatively good anti-tumor effect and good in-vivo tolerance.

The invention discloses a method, a system and equipment for evaluating the treatment effect of PTT on pancreatic cancer. According to the application disclosed by the invention, PTT is found to treat pancreatic cancer by regulating a caspase-1 / GSDMD pathway for the first time, and the expression level of GSDMD is found to be in positive correlation with the drug resistance of pancreatic cancer cells to 5-fluorouracil, irinotecan, paclitaxel and cis-platinum, which prompts that people can adopt a local treatment method of photothermal therapy instead of traditional chemotherapy for patients with high expression of GSDMD. Besides, the invention provides a method, a system and equipment for evaluating the treatment effect of PTT on pancreatic cancer and a method, a system and equipment for predicting the sensitivity of pancreatic cancer patients to chemotherapeutics, thereby assisting doctors in evaluating the treatment effect of pancreatic cancer patients and guiding clinicians to formulate individualized treatment schemes for patients.

Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein.Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant.Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone. Relacorilant and such reduced doses of paclitaxel may be co-administered to treat cancer, e.g., ovarian or pancreatic cancer.

The invention discloses a culture medium composition for culturing GDT cells and a culture method, and belongs to the field of biological medicine. Aiming at the problems of low in-vitro amplification efficiency and poor function of the existing GDT cells, the invention provides the culture medium composition for culturing the GDT cells, the culture medium composition comprises an induction culture medium and a proliferation culture medium, the induction culture medium comprises a basic culture medium and an activating agent, and the activating agent comprises IL-7 and paclitaxel; the proliferation culture medium comprises a basic culture medium, IL-18 and a metabolism regulator. An STAT5 pathway is activated through IL-7, and amplification of the Vdelta2 subgroup is specifically promoted; on the other hand, through the cooperation of the IL-7 and the IL-18, the IL-18 activates the expression of the NKG2D, and the IL-18 and the IL-7 jointly enhance the cytotoxicity; efficient amplification and function enhancement of the GDT cells are achieved; the killing rate of PD-L1 + tumor cells is larger than 80%, the motility rate after cryopreservation recovery is larger than 90%, the function maintenance rate is larger than 85%, and the cell line is suitable for tumor immunotherapy, infectious disease treatment and cell drug development.

The utility model provides a paclitaxel albumin nanoparticle preparation continuous ultrafiltration system which comprises a first SPTFF ultrafiltration module, a constant-flow water replenishing device and a static mixer, and a three-way valve is arranged on a connecting pipeline of an inlet of the static mixer. The three-way valve is respectively connected with an inlet of the static mixer, an outlet of the first SPTFF ultrafiltration module and an outlet of the constant-flow water replenishing device; and an inlet of the second SPTFF ultrafiltration module is connected with an outlet of the static mixer. According to the continuous ultrafiltration system for the paclitaxel albumin nanoparticle preparation, provided by the utility model, the front-end feeding amount can be adjusted according to the production batch, and the original fixed process can be adjusted into a linear process within a registration range, so that the flexibility of the production process is improved; when the system is used for production, liquid medicine emulsified and homogenized at the front end can be subjected to ultrafiltration concentration and elution in real time to a subsequent process, and extra waiting is not needed; and moreover, the frequency of manually switching on and off the ultrafiltration system is reduced, and the risk of misoperation of personnel is reduced.

The invention belongs to the technical field of health-care products, and provides nano donkey-hide gelatin oral liquid and a preparation method thereof. The preparation method comprises the following steps: S1, crushing colla corii asini, mixing the crushed colla corii asini with a surfactant solution, and performing ultrasonic treatment to obtain coated colla corii asini particles; s2, mixing jujubes, Chinese wolfberry fruits and haws, crushing to obtain a mixture, mixing the mixture, the coated donkey-hide gelatin particles and water, and extracting to obtain an extracting solution; s3, concentrating the extracting solution to obtain a concentrated solution; s4, mixing the concentrated solution, psicose and astaxanthin, and performing nanoscale homogenization treatment to obtain the nano donkey-hide gelatin oral liquid. A layer of protective film is formed on the surface of the donkey-hide gelatin fine powder through a surface modification technology, so that the agglomeration phenomenon of the donkey-hide gelatin in the extraction process is effectively prevented. The donkey-hide gelatin particles are further refined through high-pressure homogenization treatment, so that the donkey-hide gelatin particles reach the nanoscale, and the solubility and bioavailability of the donkey-hide gelatin are remarkably improved.

The invention provides a dihydroisoflavone compound, a preparation method and application thereof, a derivative of the dihydroisoflavone compound, application of the derivative and a pharmaceutical composition, and relates to the technical field of medicines. The dihydroisoflavone compound and the derivative thereof provided by the invention have a remarkable inhibition effect on triple-negative breast cancer cells, and the half inhibition concentration value of the dihydroisoflavone compound on the triple-negative breast cancer cells is 0.86 mu M and is equivalent to that of a positive drug paclitaxel; a new choice, a new thought and a technical support are provided for developing the medicine for treating the triple negative breast cancer, and the medicine has important clinical application value.

The invention discloses a novel application of beautiful millettia root polysaccharide as a synergist of an anti-tumor drug, and particularly relates to a combination of the beautiful millettia root polysaccharide and the anti-tumor drug paclitaxel, so that the anti-tumor effect of the paclitaxel can be improved. The invention further discloses a preparation method of the beautiful millettia root polysaccharide, and a detection method of the antitumor effect of the beautiful millettia root polysaccharide. The preparation method comprises the following steps: boiling a beautiful millettia root medicinal material, filtering, concentrating and centrifuging to obtain a first supernatant and a first precipitate; adding a proper amount of water into the first precipitate for dissolving, adjusting the pH to 2-4 by using hydrochloric acid, and centrifuging again to obtain a second supernatant; combining the first supernatant and the second supernatant, adding NaOH to adjust the pH value to 6-7, performing vacuum concentration, adding anhydrous 90% ethanol for precipitation, and performing suction filtration to obtain a second precipitate; washing the second precipitate with a solvent to obtain crude extract beautiful millettia root polysaccharide; finally, step-by-step elution is conducted through an ion exchange column, and purified beautiful millettia root polysaccharide is obtained after vacuum drying.

The invention belongs to the technical field of medicines, and discloses preparation and application of a paclitaxel-loaded liposome nano targeting preparation. The paclitaxel-entrapped nano-particles are prepared by adopting a film dispersion method, and micromolecular hyaluronic acid is entrapped on the surfaces of the lipid nano-particles by utilizing the charge effect. The bionic nano-drug provided by the invention is helpful for solving the problems of poor solubility, low bioavailability, high toxicity and the like of the anticancer drug paclitaxel. The hyaluronic acid has affinity with a glycoprotein CD44 receptor on the surface of a tumor cell, so that the nanoparticles are targeted and concentrated at a tumor part, the anti-tumor effect is improved, and the systemic toxicity of paclitaxel is reduced. The preparation process is simple, the cost is low, the stability is good, the repeatability is high, and the preparation method also has a better development prospect in the aspect of clinical application transformation.

The invention relates to the technical field of medicines, and particularly provides an active oxygen responsive paclitaxel prodrug which has a structure as shown in a formula I or a formula II. Aiming at the problem of hydrophobic aggregation of paclitaxel, the paclitaxel drug is modified, the water solubility of the modified paclitaxel drug is greatly enhanced, the self-assembly performance is obtained, the modified paclitaxel drug can be self-assembled in an aqueous solution to obtain the nano particles, and the nano particles have ultrahigh drug loading capacity and drug loading efficiency. The paclitaxel nano-preparation prepared by the method can be used for preparing the paclitaxel nano-preparation, can specifically respond to high-concentration active oxygen in a tumor microenvironment, not only can improve the insufficiency of drug loading capacity of a traditional paclitaxel nano-preparation, but also can respond to release paclitaxel at a tumor position, is beneficial to reduction of drug dosage and reduction of toxic and side effects, and has important significance on improvement of patient prognosis and prolonging of patient lifetime.

The invention discloses a paclitaxel drug process parameter optimization method, device and system and a storage medium. The paclitaxel drug process parameter optimization method comprises the steps of obtaining a basic data set of paclitaxel drug production; performing data enhancement on the basic data set to generate a virtual sample expansion data set; optimizing the initial weight and bias of the BP neural network through a genetic algorithm; training the optimized BP neural network by adopting the virtual sample expansion data set; and reversely searching an optimal parameter combination in a prediction result of the optimized BP neural network by using a genetic algorithm. By adopting the technical scheme provided by the invention, the technological parameters of the production of the paclitaxel medicine for injection are optimized, and a parameter group which meets the particle size and particle size distribution and is high in binding rate is found. And through AI energizing enterprise production, the medicine production efficiency is improved, and the enterprise production cost is reduced.

The invention relates to the technical field of medical instruments, in particular to a paclitaxel drug coating balloon dilatation catheter and a preparation method and application thereof.The paclitaxel drug coating comprises a substrate layer, a middle layer and an outer layer; the substrate layer comprises paclitaxel and a hydrophilic excipient; the middle layer comprises a lipophilic excipient and a temperature response type polymer; and the outer layer comprises a pH sensitive polymer. The substrate layer is combined with the surface of the balloon, so that excellent conveying stability is provided, the medicine is effectively prevented from falling off prematurely in the conveying process of the catheter, and the firmness of the coating is improved; a micropore network structure is formed in the middle layer, the network structure is expanded under the body temperature condition, the porosity is increased, slow release of the medicine is achieved, the absorption amount of the medicine on the blood vessel wall is effectively increased, and the medicine effect time is prolonged; the solubility of the outer layer is improved in a slightly acidic blood vessel wall environment, so that the release of the medicine is further promoted, and the effective release of the medicine on the blood vessel wall is ensured.

The invention belongs to the technical field of pharmaceutical preparations. The invention discloses a multifunctional bionic nano preparation, a preparation method and application. According to the multifunctional bionic nano preparation, the ginsenoside Rg3 has the dual functions of a medicine and a membrane stabilizer, the platelet membrane has the natural targeting capability on circulating tumor cells and metastases, and meanwhile, the cationic liposome is used for adsorbing negatively-charged NETs nucleic acid protein compounds, so that potential reversal and active targeting are achieved, and the multifunctional bionic nano preparation has a good application prospect. And by co-carrying paclitaxel (PTX) and a photothermal agent (PCP) and integrating photothermal-chemotherapy-immunogenic death (ICD) induction functions, the tumor-related fibroblast activation can be effectively inhibited, circulating tumor cells can be efficiently captured, a tumor immune microenvironment can be remodeled, the tumor cells can be effectively killed, and tumor distal metastasis can be inhibited.

The invention discloses a tumor treatment molecule with a curative effect self-amplification function. Belongs to the technical field of biotechnology and new medicine, and comprises a peptide sequence Ac-Asp-Glu-Val-Asp-Cys (StBu)-Lys combined to a CBT part and a paclitaxel chemotherapy molecule connected to a lysine side chain. After the probe enters a tumor cell, the probe is specifically recognized by reducing glutathione highly expressed in the tumor cell, and an Ac-DEVDCK (PTX)-CBT structure is generated; then, a weak cell apoptosis phenomenon is initiated through a molecular grafted paclitaxel structure; the Ac-DEVD fragment is used as a high-specificity polypeptide substrate of cysteine-aspartic acid specific protease 3 which is necessary in a cell apoptosis pathway, and can be specifically cut by the cysteine-aspartic acid specific protease 3, so that the Ac-DEVDCK (PTX)-CBT is converted into CK (PTX)-CBT; then, CK (PTX)-CBT molecules are subjected to a CBT-Cys click reaction to form a cyclic dimer, and the cyclic dimer is self-assembled to form particles. According to the method, the affinity of the paclitaxel to the tubulin in the cytoskeleton is utilized, so that the tubulin in the cell is aggregated, the self-amplification effect of the curative effect of the cell is realized, and the cell is triggered to generate a pan-apoptosis effect.

The invention discloses an RGD modified crocetin-paclitaxel co-drug-loaded compound liposome and a preparation method and application thereof, and belongs to the technical field of biological medicines.The RGD modified crocetin-paclitaxel co-drug-loaded compound liposome comprises the following components: an RGD modified liposome, paclitaxel and crocetin, wherein the RGD modified lipidosome is used as a drug carrier, paclitaxel and crocetin are delivered to prostate tumor cells in a targeted manner, and the RGD modified lipidosome is prepared through a film dispersion method or a reverse evaporation method. The prostate cancer targeted compound liposome prepared by the invention can increase the uptake of prostate cancer cells, improve the in-vitro cytotoxicity of the prostate cancer cells to the prostate cancer cell line RM-1, inhibit the growth of RM-1 ectopic solid tumors in mice, and do not cause obvious damage to other tissues.

The invention provides albumin-paclitaxel twin drug nanoparticles based on peptide linkers and application of the albumin-paclitaxel twin drug nanoparticles, the linker between paclitaxel and drug molecules is a dipeptide linker, the stability of the linker is higher, and the breakage speed in tumor microenvironment response is higher. The twin drug nanoparticles synthesized by different connexons between paclitaxel and drug molecules are compared and analyzed, and dipeptide connexons capable of effectively improving the anti-tumor effect of the albumin-paclitaxel twin drug nanoparticles are screened, so that efficient co-loading of multiple drugs is realized, accumulation of the drugs is increased, and indiscriminate killing of the drugs on normal cells is reduced; the target of treating and fading tumors is achieved, and the current curative effect bottleneck of malignant tumors is expected to be broken through.

The invention discloses a sorafenib-paclitaxel combined prodrug as well as a preparation method and application thereof, and relates to the field of chemical pharmacy, a prodrug strategy is utilized, sorafenib and paclitaxel are covalently linked through a disulfide bond, and an S-PTX drug is successfully prepared. The drug can be self-assembled to form stable nanoparticles in an aqueous solution system containing 1% of absolute ethyl alcohol and 1% of polyoxyethylated castor oil by means of hydrophobic interaction, Van der Waals force and the special chemical properties of disulfide bonds. According to the invention, the drug delivery is carried out without any additional carrier, so that the problem of carrier toxicity when the carrier is introduced into the traditional nano delivery system is avoided, the safety of the drug in in-vivo application is greatly improved, and a solid and reliable foundation is provided for subsequent clinical treatment. The sorafenib-paclitaxel combined prodrug S-PTX prepared by the invention effectively solves the problem of drug resistance caused by medication of a single drug.

The invention belongs to the technical field of medicinal chemistry, and particularly discloses a novel tubulin and metalloproteinase double-target inhibitor as well as a preparation method and application of the novel tubulin and metalloproteinase double-target inhibitor. A novel tubulin and metalloproteinase double-target inhibitor is obtained as a compound with a targeting function. A verification result shows that the synthesized target compound shows good anti-proliferative activity on tested cancer cells, 15j has the optimal anti-tumor activity, the IC50 value range of the target compound is 0.154-0.296 mu M, and the tumor inhibition rate of the target compound on human lung cancer transplantation tumors is 74.7% (20 mg / kg). Besides, the anti-proliferative activity of the 15j to cis-platinum drug-resistant cells A549 / CDDP is 136.70 times that of the cis-platinum, the anti-proliferative activity of the 15j to adriamycin drug-resistant cells MCF-7 / DOX is 71.14 times that of the adriamycin, and the toxicity of the 15j to human normal cells (LO2 and MCF-10A) is lower than that of positive drugs such as the cis-platinum, the adriamycin and the paclitaxel. Therefore, the compound has the potential purpose of targeted treatment of lung cancer.

One embodiment of the present invention provides a psicose epimerase expression cassette comprising a polynucleotide encoding a psicose epimerase and a promoter operably linked thereto and modulating the expression of the psicose epimerase in a Corynebacterium strain. The promoter consists of a base sequence as shown in a sequence 1, a base sequence as shown in a sequence 9, a base sequence as shown in a sequence 10 or a base sequence as shown in a sequence 11. The psicose epimerase expression cassette disclosed by the embodiment of the invention is almost not started in a normal environment for culturing a recombinant corynebacterium strain, and does not induce growth inhibition of the recombinant corynebacterium strain. Therefore, the recombinant corynebacterium strain transformed by the psicose epimerase expression cassette of one embodiment of the present invention can normally grow and proliferate to the logarithmic phase, and stably and highly express psicose epimerase after the logarithmic phase.

The invention discloses a small molecular twin drug compound with a synergistic analgesic effect and a pharmaceutical composition, a preparation method and application thereof. The twin drug molecule is formed by connecting a drug A and a drug B through a covalent bond, the drug A is nefopam, and the drug B is gamma-aminobutyric acid (GABA) and analogues thereof and comprises gabapentin, pregabalin, GABA, melogabalin and crigabalin. The analgesic effect of the composition is superior to that of combined administration and single administration, and the composition can obviously improve various acute and chronic inflammation pains and can relieve paclitaxel-induced peripheral neuralgia; the anti-inflammatory activity is higher than that of combined use and single drug, so that the compound has the potential of treating pain, inflammation and inflammatory pain related diseases; the interaction among the medicines can be effectively reduced, and the medication compliance of a patient is improved.

A Bacillus amyloliquefaciens strain MHDS-1 and use thereof in processing of Taxus media are provided, belonging to the technical field of microorganisms. The Bacillus amyloliquefaciens strain MHDS-1 herein is deposited in the China Center for Type Culture Collection (CCTCC) with a deposit number of CCTCC NO: M20231262. The strain is used to process the Taxus media, and can effectively increase a paclitaxel content of the Taxus media, which is not less than 20% higher than that of unprocessed Taxus media.

The invention discloses an NK cell membrane coated prodrug self-assembly nanoparticle as well as a preparation method and application thereof. The prodrug self-assembled nanoparticles are formed by self-assembling a bufalin carbonate prodrug and a paclitaxel carbonate prodrug independently or jointly through a nanoprecipitation method. The preparation method comprises the following steps: preparing bufalin carbonate prodrug, paclitaxel carbonate prodrug or double-prodrug self-assembled nanoparticles wrapped by an NK cell membrane, and further performing ultrasonic extrusion on the NK cell membrane, so that the nanoparticles are simple in preparation process and high in drug loading capacity. In-vitro cell experiments prove that the NK cell membrane can obviously improve the tumor cell uptake efficiency of the prodrug nanoparticles, enhance the anti-tumor effect of the prodrug nanoparticles, reduce acute toxicity and improve the administration safety, and can be further applied to clinical research in the future.

The present invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), in particular two classes allosteric inhibitors of ALC1 (CHD1L), of Formula (I) and Formula (II), that show a potentiating, preferably additive effect in the treatment of proliferative disease when combined with several classes of cancer drugs, namely inhibitors of Topoisomerase I, Topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with mitomycin C, paclitaxel, with ionizing radiation, or with an antibody drug conjugate with a tumor specific antibody conjugated to a TOP1 inhibitor. Furthermore, the present invention relates to said inhibitors of ALC1 of Formula (II) that show a synergistic effect in the treatment of pancreatic cancer or fallopian tube cancer when combined with a PARP inhibitor (Poly(ADP-ribose)-Polymerase inhibitor (PARPi)). By being synergistic with the function of said cancer drugs, said ALC1 inhibitors, in particular those of Formula (I) and Formula (II), potentiate the cancer cell killing properties of the aforementioned cancer drugs, in particular enabling therapeutic approaches where any of the aforementioned inhibitors is already used as part of the standard of care.