4358results about "In-vivo testing preparations" patented technology

The present application provides a method for diagnosing and / or evaluating the presence or absence, severity or degree of the improvement of a retinal disease in a subject, which comprises determining and / or evaluating circulatory parameters, retinal function, retina morphology and / or visual relating quality of life (QOL).

This disclosure relates to a method of treating depression and / or reducing risk of suicide, comprising administering a combination of about 90 mg to about 120 mg of bupropion hydrochloride, or a molar equivalent amount of another form of bupropion, and about 40 mg to about 50 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another form of dextromethorphan. The combination may be administered twice a day to a human being suffering from major depressive disorder and having a score of 3 or greater on the Suicidality Item of the Montgomery-Åsberg Depression Rating Scale (MADRS-SI).

The invention is based, at least in part, on the discovery that replacement of a key bond in the near-infrared fluorophore with a carbon-carbon bond conjugation to a targeting ligand results in vastly increased stability as compared to NIR fluorophores without such a bond, while preserving ligand and zwitterionic properties. In at least one aspect, the invention provides an imaging agent dye comprising a charge-balanced imaging agent conjugated to a targeting vector, wherein the targeting vector is a PSMA binding vector, such as dPSMA-617 or KUE, a FAP binding vector, a bombesin receptor binding vector, or a somatostatin receptor binding vector, and the charge-balanced imaging agent is ZW-800-1, ZW-830-1, or ZW-700-1-Forte.

The invention discloses an MOF-CQD enzyme-sensitive FRET hydrogel diagnosis and treatment probe as well as a preparation method and application thereof, and belongs to the technical field of biomedical detection and treatment. The probe takes a carboxyl carbon quantum dot (CQD) as a donor and a metal organic framework (MOF) as an acceptor, and the donor and the acceptor are connected through a replaceable enzyme response polypeptide bridge; when the fluorescence is complete, FRET is generated to quench the CQD fluorescence, the FRET is interrupted after the target enzyme cuts off the peptide bridge, and the blue / red fluorescence ratio is changed to realize nanomole-level quantitative detection and has self-correction capability. The probe is packaged in a four-arm PEG transparent hydrogel which does not need a photoinitiator and can be quickly self-crosslinked, and can be prepared into a film, a tooth socket and the like for POCT (point-of-care testing) of parts such as an oral cavity / skin and the like. After detection, the MOF is activated by illumination of 630-660 nm to generate active singlet oxygen, so that local antibacterial or anti-tumor treatment is realized, and a diagnosis and treatment integrated scheme is constructed.

The invention discloses a fluorescent composite nano material as well as a preparation method and application thereof, and belongs to the technical field of fluorescent materials. The fluorescent composite nano-material provided by the invention comprises carbon quantum dots with carboxyl modified surfaces and fluorescent nano-particles with amino modified surfaces, wherein the mass ratio of the carbon quantum dots to the fluorescent nano-particles is (0.8-3): 1; the carbon quantum dots of which the surfaces are modified with carboxyl groups are connected with the fluorescent nanoparticles of which the surfaces are modified with amino groups through amido bonds formed by dehydration condensation of carboxyl groups and amino groups; the molecular formula of the fluorescent nanoparticles is Cs2NaYCl6: Yb < 3 + > / Eu < 3 + >, the molar concentration of doped Yb < 3 + > is 15-25%, and the molar concentration of doped Eu < 3 + > is 8-12%. The fluorescent composite nanomaterial provided by the invention has the advantages of uniform particle size and high fluorescence emission intensity, has good fluorescence stability, and can be applied to the fields of humidity detection, fluorescence imaging and the like.

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

The invention relates to the field of nano-drug delivery preparations, in particular to a traditional Chinese medicine transdermal drug delivery preparation based on a nano-coating technology and a preparation method thereof, the traditional Chinese medicine transdermal drug delivery preparation comprises a liposome-metal organic framework composite carrier, and the composite carrier comprises traditional Chinese medicine active ingredients; a meridian point targeted transdermal enhancer; an iontophoresis device for dynamically sensing skin impedance; the invention relates to an intelligent administration time sequence control system based on a traditional Chinese medicine midnight-noon ebb-flow theory. The liposome-metal organic framework composite carrier is adopted, the similar structure of liposome and skin and the high specific surface area of MOF are fully utilized, efficient encapsulation and transdermal absorption of active ingredients of traditional Chinese medicine are achieved, and compared with a traditional transdermal patch, the drug transdermal absorption rate is increased by 3-5 times.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

The invention provides an establishment method of a transgenic mouse, and the method comprises the following steps: a transgenic mouse MHC chimeric gene is introduced into an endogenous B2m gene locus of the mouse, the MHC chimeric gene comprises a human B2M gene and a chimeric alpha-chain gene, and the chimeric alpha-chain gene comprises a human alpha1 region, a human alpha2 region and a mouse alpha3 region; the chimeric alpha-chain gene further comprises a mouse transmembrane region and a mouse intracellular region. The transgenic mouse disclosed by the invention can be applied to tumor specific antibody detection, in-vivo evaluation of vaccines, and in-vivo screening of TCR-T and other drugs.

The invention belongs to the technical field of cosmetic efficacy evaluation, and discloses a sunscreen efficacy evaluation method and application thereof, and the method comprises the following steps: building a blank group; establishing a model group; establishing a sample group; performing constant-temperature incubation on the blank group, the model group and the sample group for a first period of time, recording a swimming track, and calculating swimming distance increment and after-sun burning pain relieving efficiency of each group of zebrafish; performing constant-temperature incubation on the blank group, the model group and the sample group for a second duration, recording the tail fin and dorsal fin area of the zebra fish, and calculating the sunburn prevention efficiency; performing constant-temperature incubation on the blank group, the model group and the sample group for a third period of time, recording the head melanin area of the zebra fish, and calculating the anti-sunburn efficiency; and grading the sunscreen effect of the sample. The method disclosed by the invention has the advantages of low cost, short test period, high reproducibility, high visualization degree, intuitive and understandable test result and the like, and can be used for accurately grading the sunscreen effects of chemical sunscreen agents, water-soluble sunscreen cosmetics and raw materials thereof from the whole animal level.

The invention discloses a dual-mechanism antibacterial photosensitizer as well as a preparation method and application thereof, and relates to the technical field of biomedical photoelectric functional materials. The invention relates to a triphenylamine derivative, which can realize fluorescence imaging of bacterial or fungal infection by utilizing fluorescence characteristics, can generate active oxygen under illumination to play a photodynamic therapy role, is suitable for preparing photodynamic therapy preparations and developing antibacterial materials, and can also be applied to the fields of environment and public health and tumor treatment. The problems that an existing photosensitizer is insufficient in broad spectrum, different in fungus drug resistance mechanism, limited in single treatment effect and the like can be effectively solved, and the photosensitizer has wide application prospects.

An x-ray apparatus and method can improve x-ray imaging in a variety of ways. For example, the improve x-ray apparatus can reduce scatter from x-ray images acquired by two-dimensional detectors. An improved 2D x-ray apparatus can provide 3D imaging for medical and / or industrial applications. An improved 2D x-ray apparatus and method can produce separate material imaging, and composition analysis for characterization and correlation of image, densitometry, and composition information of individual component or individual material within a single subject. Non-rotational 3D microscopy, combining 2D or 3D full field x-ray imaging and high resolution 2D or 3D x-ray microscopy or spectral absorptiometry and spectroscopy can achieve a higher resolution and wider field of view in x-ray imaging and quantitative analysis in 3D and real time. The x-ray apparatus can improve tracking and / or surgical guidance in time and / or space.

The invention provides immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions and methods thereof.

The invention provides an ER targeting self-assembly AIE probe with cascade ROS / RNS generation performance, and belongs to the technical field of material chemistry, the probe is composed of four units: 1) an AIE photosensitizer OTBS used for generating ROS; 2) deriving peptide FFVLK from beta amyloid protein, and promoting the self-assembly of the peptide to form a nanofiber with a beta-sheet structure; (3) an oligomerization arginine unit RRRR which is used as an NO donor; and 4) ER targeting signal peptide KDEL to endow ER with targeting ability. Based on ER targeting and a self-assembly process, the self-assembly AIE probe is subjected to ER in-situ self-assembly in cells to form nanofibers, ROS / RNS is generated in a cascading manner under illumination, and strong ICD is induced. In addition, the tumor residence time of the photosensitizer is prolonged due to the formation of the nanofibers, and the treatment effect is further improved. The invention provides a new thought for the design of a novel light-operated II-type ICD inducer.

Disclosed in the present invention are an HLA-A*11-targeted liver cancer mRNA vaccine, and a preparation method therefor and a use thereof. The mRNA vaccine of the present invention is an mRNA vaccine designed on the basis of the HLA-A*11:01 typing of a patient and having high-coverage and high-immunogenic tumor neoantigens, and is formed by transcribing DNA having a nucleotide sequence shown in SEQ ID NO: 32 to form an mRNA, and encapsulating the mRNA in lipid nanoparticles.

The invention belongs to the technical field of biological medicines, and discloses a DSH loaded medicine as well as a preparation method and application thereof. The DSH loading type medicine is DNA (Deoxyribonucleic Acid) supramolecular hydrogel loaded with 2, 2, 6, 6-tetramethylpiperidine-1-oxide, and the DSH loading type medicine is a DNA supramolecular hydrogel loaded with the 2, 2, 6, 6- Wherein the DNA supramolecular hydrogel is formed by assembling a Y type DNA monomer and an L type DNA monomer. The DSH loaded medicine has good anti-inflammatory and peroxy free radical removing effects, and can achieve the purpose of treating knee osteoarthritis. In addition, the DSH loaded medicine can be used for reflecting the content of peroxy free radicals in knee joints by detecting the contrast ratio of knee joint images through magnetic resonance, and early diagnosis of knee osteoarthritis is achieved.

The invention discloses an acid responsive nanoprobe as well as preparation and anti-tumor application thereof. The nanoprobe has a core-shell structure, takes a nanoparticle self-assembled by a polycation aggregation-induced emission (AIE) photosensitizer and functional nucleic acid as a core, and takes a hyaluronic acid modified metal polyphenol network as a shell. The nanoprobe utilizes the acid responsiveness and broad-spectrum absorption performance of the metal polyphenol network and the diagnosis and treatment advantages of the polycation AIE photosensitizer to realize the acid responsiveness'switch 'controllable diagnosis and treatment of the tumor nanoprobe. In a neutral environment, the fluorescence is weak, the generation of ROS is less, and the background noise signal of the nanoprobe and the toxicity of non-targeted tissues are reduced; in an acid environment, fluorescence is enhanced, the ROS yield is improved, and the treatment efficiency and the curative effect monitoring accuracy are improved. The nano diagnosis and treatment probe is ingenious in design and simple to prepare, and can realize PDT and gene therapy synergistic anti-tumor, in-situ real-time report of early tumor treatment effect and assistance in precise cancer treatment.

The invention relates to the technical field of luminescent materials, and discloses an aggregation-induced emission material, nanoparticles as well as a preparation method and application thereof, the structural general formula of the aggregation-induced emission material is as follows: # imgabs0 #, R is selected from one of the following structures: # imgabs1 # aggregation-induced emission material takes a pyridine group as an acceptor unit, and the acceptor unit is selected from one of the following structures: 1 # imgabs2 # aggregation-induced emission material; a carbon-carbon double bond and a thiophene unit are used as pi bridges, and diphenylamine, bis (4-ethylphenyl) amine and bis (4-(tert-butyl) phenyl) amine are used as strong electron donors. The donors not only provide strong electron supply ability, but also become efficient rotors due to highly twisted molecular conformation, and endow the aggregation-induced emission material with long emission wavelength and aggregation-induced emission activity.

The invention provides an electrochemical luminescence MeHA microneedle patch and a preparation method and application thereof.The preparation method comprises the steps that hyaluronic acid is modified into methacrylated hyaluronic acid, MeHA solid powder is obtained after purification, and the MeHA solid powder is mixed with a photoinitiator to form a precursor solution; and pouring into a microneedle mold, centrifuging, drying and carrying out UV crosslinking to obtain the MeHA microneedle patch loaded with ABEI and glucose oxidase. Through the MeHA microneedle patch-SPE electrode integrated design, the integrated operation of skin interstitial fluid in-situ extraction-enzymatic reaction-electrochemical luminescence detection is realized, sample transfer is not needed, the interference of intermediate links is greatly reduced, the detection accuracy and efficiency are remarkably improved, and the device and the method are particularly suitable for clinical real-time monitoring scenes.

The invention discloses a near-infrared two-region activatable probe as well as a preparation method and application thereof. The near-infrared second-region activatable probe comprises a near-infrared second-region fluorescent light-emitting unit and an analyte specific response unit; the near-infrared second-region light-emitting unit comprises a hemicyanine fluorophore structure; when the analyte specific response unit is chemically coupled with the near-infrared second-region light-emitting unit, the intramolecular charge transfer process of the light-emitting unit can be inhibited, and fluorescence quenching is caused; the analyte specific response unit is separated from the light-emitting unit after being subjected to specific reaction with an analyte, so that fluorescence is activated. The near-infrared two-region hemicyanine fluorophore selected by the near-infrared two-region activatable probe has higher fluorescence quantum efficiency, and the near-infrared two-region probe which can be activated by a specific analyte and has a high on-off ratio can be constructed by introducing an analyte specific response unit, so that high-temporal-spatial-resolution fluorescence detection of deep tissues can be realized; the method has a wide application prospect in the field of biomedical detection.

Disclosed are methods of improving perioral and face fat graft retention in a subject by administering a therapeutic MSC secretome product made by a method comprising culturing bone marrow-derived MSCs under conditions that include oxygen tension below 5% and a culture media with a pH below 7.

The invention discloses an aggregation-induced emission near-infrared photothermal molecule as well as a preparation method and application of the aggregation-induced emission near-infrared photothermal molecule, and belongs to the technical field of biomedicine. The invention provides the preparation method of the aggregation-induced emission near-infrared photothermal molecule, the synthesis process is simple and efficient, and the obtained novel near-infrared photothermal molecule has better luminescence performance or photothermal performance of a near-infrared second region. Meanwhile, the near-infrared aggregation-induced emission protein nanoparticles provided by the invention are simple in preparation process and excellent in performance, and can effectively cross nasal mucosa and target an A beta plaque part, so that AD visualization and photo-thermal / hypoxia relief combined treatment are realized.

The invention discloses a specific cell targeted hybrid nano-delivery carrier and a preparation method and application thereof, and aims to solve the problems of insufficient specificity, off-target risk, low delivery efficiency and the like of an existing drug delivery system. And a bionic hybrid nano delivery platform with a natural targeting function and high drug loading capacity is constructed. The vector retains key receptor molecules and signal markers on a source cell membrane, and can actively identify and target corresponding cells; meanwhile, due to the introduction of the lipidosome, the yield and stability of the material are remarkably improved, and the immune clearance rate is reduced. Experimental results show that the nano-carrier shows good targeting and biocompatibility in various disease models, and has wide clinical application prospects in the aspects of tumor treatment, tissue repair, inflammation control, targeted imaging and the like.

The invention discloses a construction method and application of a mouse model for specifically tracing heart valve cells, and belongs to the technical field of animal model construction. The model construction method comprises the following steps: (1) constructing a Wid1-Cre hybrid mouse before inserting a Cre recombinase coding gene into a termination codon of a mouse Wid1 gene; and (2) hybridizing the Wid1-Cre hybrid mouse with the Rosa26-tdTomato homozygous report mouse, so as to obtain the double transgenic mouse which simultaneously carries the Wid1-Cre gene and the Rosa26-tdTomato gene. According to the invention, on the basis of the expression characteristic that Wif1 is only limited to a valve area in the heart, Wif1-Cre is constructed; according to the Rosa26-tdTomato mouse model, specific tracing of heart valve cells is achieved, and an important experimental tool is provided for mechanism research of heart valve diseases and development of therapeutic drugs.

The invention relates to the technical field of pharmaceutical preparations, in particular to a preparation process of carbon dots for killing helicobacter pylori and application of the carbon dots in oral pharmaceutical preparations. The preparation method comprises the following steps: mixing microcrystalline cellulose and glycerol, freezing and crushing at an ultralow temperature, and selectively hydrolyzing by combining citric acid-malic acid mixed acid liquor to efficiently prepare a high-crystallinity cellulose nanocrystal template; the controllable synthesis of the carbon dots is realized by utilizing the hydrogen-bond interaction of hydroxyl / carboxyl on the surface of the cellulose nanocrystal and the nitrogen doping effect in the polymerization and carbonization process of citric acid and urea. Besides, when a sodium alginate-chitosan double-layer structure is constructed, carbon dots are introduced into the inner layer to endow the inner layer with special performance, a protein-polysaccharide network is formed on the outer layer through transglutaminase enzymatic crosslinking, and the oxidation resistance and mechanical strength are enhanced through secondary curing of tea polyphenol. According to the invention, food-grade raw materials are used for realizing high-efficiency antibiosis, the oral preparation safety specification is met, and the clinical transformation potential is realized.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

The invention discloses a Parkinson's disease animal model, a construction method and application, and relates to the field of animal genetic engineering and disease model construction. According to the model, seven mutation sites related to the human familial Parkinson's disease are introduced behind an initiation codon of a fourth exon of an endogenous SNCA gene, and the mutation sites are A18T, A29S, A30P, E46K, H50Q, G51D and A53T and have genotypes related to the human familial Parkinson's disease. The pig model shows nigra dopaminergic neuron reduction and cortical neuron reduction in the newborn period, and the core pathological process of the human Parkinson's disease can be systematically reproduced. The model can be widely applied to Parkinson's disease pathogenesis research, drug screening and cell therapy effect evaluation, and has important scientific research and preclinical application values.

The invention relates to the field of biomedicine, particularly provides a copper-based nano-enzyme as well as a preparation method and application thereof, and aims to solve the problems that in the prior art, clinical treatment on primary sclerosing cholangitis (PSC) is difficult in diagnosis and lacks of effective treatment drugs. The copper-based nano-enzyme comprises a nano-enzyme carrier and a copper-based nano-enzyme, wherein the nano-enzyme carrier is a two-dimensional nanosheet formed by copper ions, gallic acid and ursodesoxycholic acid through coordinate bonds; the probe molecule is a cyanine dye molecule connected to the surface of the nano-enzyme carrier through a covalent bond; wherein the fluorescence intensity of the copper-based nano enzyme is enhanced after the action of the alkaline phosphatase. The three functions of alkaline phosphatase responsive diagnosis, nano-enzyme catalytic treatment and ursodesoxycholic acid hepatic targeting are innovatively and synergistically integrated into one nano platform, the treatment function can be executed while specific imaging diagnosis is performed on diseases, and a new strategy is provided for diagnosis and treatment of diseases such as PSC.

The invention discloses a near-infrared two-region aggregation-induced emission material as well as a preparation method and application thereof, and belongs to the technical field of aggregation-induced emission materials. The invention provides a fluorescent material with aggregation-induced emission (AIE) property, which can have high luminous efficiency in an NIR-II (1000 nm to 1500 nm) region. The invention aims to carry out rational structure design through the multilevel space confinement effect of molecule and aggregate levels. Through modification of a methyl group and a side chain substituent group, free rotation of an aromatic ring is effectively inhibited, and a rigid mortise and tenon interlocking structure is formed in the crystal. The water-soluble nanoparticles prepared from the synthesized aggregation-induced emission material can achieve a fluorescence quantum yield of 28.2%. By utilizing the nanoparticles with high fluorescence efficiency, the application of real-time dynamic monitoring and the like on intestinal vessels of a living body can be realized, and a new method is provided for early diagnosis and surgical intervention of acute intestinal ischemia.

The invention belongs to the technical field of organic dye synthesis and application, and discloses a conjugated compound containing a benzothiophenazine structure as well as a preparation method and application thereof, and the conjugated compound containing the benzothiophenazine structure has excellent photophysical properties, singlet oxygen yield and superoxide anion generation capacity. The novel conjugated compounds ENBO-NI and ENBS-NI containing benzothiophenazine structures are successfully prepared by replacing a benzene ring of Nile blue with a cycloalkane structure and adjusting the electron donating ability of an R1 group. The two compounds have near infrared fluorescence emission, good solubility and relatively high ROS yield. Compared with a classical photosensitizer NB, the singlet oxygen yield of ENBO-NI is increased by about 117.65%, and the singlet oxygen yield of ENBS-NI is as high as 70%. The absorption wavelength of the conjugated compound is in a red light wave band. The preparation process is simple and efficient, large-scale production is easy, and the preparation method has a wide clinical application prospect.