233 results about "In vivo tests" patented technology

The present invention provides articles of manufacture comprising biocompatible nanostructures comprising significantly increased surface area for, e.g., organ, tissue and / or cell growth, e.g., for bone, tooth, kidney or liver growth, and uses thereof, e.g., for in vitro testing of drugs, chemicals or toxins, or as in vivo implants, including their use in making and using artificial tissues and organs, and related, diagnostic, screening, research and development and therapeutic uses, e.g., as drug delivery devices. The present invention provides biocompatible nanostructures with significantly increased surface area, such as with nanotube and nanopore array on the surface of metallic, ceramic, or polymer materials for enhanced cell and bone growth, for in vitro and in vivo testing, cleansing reaction, implants and therapeutics. The present invention provides optically transparent or translucent cell-culturing substrates. The present invention provides biocompatible and cell-growth-enhancing culture substrates comprising elastically compliant protruding nanostructure substrates coated with Ti, TiO2 or related metal and metal oxide films.

High purity water, particularly that intended for the pharmaceutical or electronics industry, is analyzed for the presence of pyrogen or other impurities by causing the water to come into contact with a direct affinity sensor, which may be a surface plasmon resonance (SPR) device or other sensor relying on an evanescent wave phenomenon. A property of the surface-refractive index in the case of SPR-changes on the binding of impurity, thereby enabling impurity to be detected. The invention overcomes the cumbersome nature and batch-to-batch variability of the conventional in vivo tests as well as the in vitro Limulus Amoebocyte Lysate (LAL) assay and for the first time allows the continuous or real time monitoring of high purity water for pyrogen.

In alternative embodiments, the invention provides articles of manufacture comprising biocompatible nanostructures comprising PolyEther EtherKetone (PEEK) surface-modified (surface-nanopatterned) to exhibit nanostructured surfaces that promote osseointegration and bone-bonding for, e.g., joint (e.g., knee, hip and shoulder) replacements, bone or tooth reconstruction and / or implants, including their use in making and using artificial tissues and organs, and related, diagnostic, screening, research and development and therapeutic uses, e.g., as primary or ancillary drug delivery devices. In alternative embodiments, the invention provides biocompatible nanostructures that promote osseointegration and bone-bonding for enhanced cell and bone growth and e.g., for in vitro and in vivo testing, restorative and reconstruction procedures, implants and therapeutics.

A Lactobacillus plantarum BB9 capable of adhering to gastrointestinal tract and cholesterol removal is isolated from fruits and exhibits high BSH activity. In-vitro tests demonstrate that Lactobacillus plantarum BB9 has good acid and bile tolerance, and strong ability to adhere to intestinal cells. In-vivo tests show that hamsters fed high cholesterol diets added with BB9 strain have cholesterol and triglycerides in blood and liver effectively reduced, and their HDL-c / LDL-c ratios in blood are significantly higher than those of hamsters fed Lactobacillus acidophilus ATCC 43121 strain. It is hoped that the excellent acid and bile tolerance and intestinal adherence of the lactobacillus strain provided herein could produce cholesterol-lowering effect in humans.

Methods, sensors, and systems for determining a concentration of glucose in a medium of a living animal are disclosed. Determining the glucose concentration may involve emitting excitation light from a light source to indicator molecules, generating a raw signal indicative of the amount of light received by a photodetector, purifying and normalizing the raw signal, and converting the normalized signal to a glucose concentration. The purification may involve removing noise (e.g., offset and / or distortion) from the raw signal. The purification and normalization may involve tracking the cumulative emission time that the light source has emitted the excitation light and tracking the implant time that has elapsed since the optical sensor was implanted. The purification and normalization may involve measuring the temperature of the sensor. The purification, normalization, and conversion may involve using parameters determined during manufacturing, in vitro testing, and / or in vivo testing.

Disclosed are systems biology-based methods for repositioning known pharmaceutical compounds to new indications, through the identification of network-based signatures. In particular, the invention provides new and useful methods for selecting drugs or combinations of drugs (and preferably previously-approved drugs) for use in new therapeutic indications. Also disclosed are methods for identifying anti-breast tumor initiating cell (TIC)-based therapeutics from within populations of target compounds. In illustrative embodiments, the invention provides methods and computer programs for the repositioning of FDA-approved pharmaceutical compounds to new indications using network-based signature analysis coupled with conventional in vitro and in vivo testing of identified drug candidates. The invention also allows identification of drugs or drug combinations for treating unmet medical needs including, for example, “orphan” diseases.

This patent describes a novel in vitro cell-based method for biological validation and pharmacological screening of drugs, new chemical entities (NCEs) and biologics, which is predictive of in vivo testing for efficacy and adverse events in patients, as occurs in clinical trials. The same method can be used to create an in vitro cell-based assay to identify the ‘right marketed medication for the right patient’ (personalized medicine), and to identify responders / non-responders in ongoing clinical trials with NCEs. In addition this approach can be used to identify new indications for existing medicines and new indications for NCEs that were unsuccessful in their intended uses.

The invention discloses application of A-nor-5 alpha-androstane compounds in preparation of malignant tumor resistant medicaments. The compounds have the following general formula I, and comprise Ia, Ib, Ic, Id, Ie and If. The growth inhibition rate of the A-nor-5 alpha-androstane compounds for in-vitro human liver cancer cell Hep 3B, human breast cancer MDA-MB-231, human lung adenocarcinoma A549 and mouse melanoma B16 is higher than 85% on average, and even up to 99.98% to the maximum. The in-vivo test proves that the inhibition rate of the A-nor-5 alpha-androstane compounds for mouse tumors, such as intestinal cancer C26, liver cancer H22, Lewis lung cancer, breast cancer, B16 melanoma and the like, is higher than 50% on average, and even up to 63.19% to the maximum. The result proves that the compounds disclosed by the invention have an obvious malignant tumor resistant action. The A-nor-5 alpha-androstane compounds disclosed by the invention have an obvious and broad-spectrum action on inhibiting growth of malignant tumor cells, and are novel targeted malignant tumor resistant medicaments with low drug toxicity and favorable treatment effect; and the A-nor-5 alpha-androstane compounds just specifically act on tumor cells, but not influence normal cells, thereby having a high clinical application value.

This invention is related to adenoviral (Ad) vectors and their applications in the field of genetic medicine, including gene transfer, gene therapy, and gene vaccination. More specifically, this invention is related to the Ad vectors that carry the minimal cis-element of the Ad genome (mini-Ad vector) and are capable of delivering transgenes and / or heterologous DNA up to 36 kb. The generation and propagation of the mini-Ad vectors require trans-complementation of a packaging-attenuated and replication-defective helper Ad (helper) in an Ad helper cell line. This invention further comprises a methodology for generating a mini-adenoviral (mini-Ad) vector for use in gene therapy of hemophilia and animal test systems for in vivo evaluation of the Ad vectors. More specifically, this invention describes factor VIII (FVIII) Ad vectors that only contain minimal cis-elements of the Ad genome (so called mini-Ad) and comprise a human FVIII cDNA with other supporting DNA elements up to 36 kb. The FVIII mini-Ad can be generated and preferentially amplified through the assistance of a packaging-attenuated helper Ad and a helper cell line. This invention also reports designs and methods for producing transgenic mouse models that can be used for in vivo testing the mini-Ad.

The present invention relates to probiotic microorganisms producing chimeric human growth hormone for oral use and methods for preparing them. The invention provides probiotic Lactobacillus or yeast transformant expressing chimeric protein which is human growth hormone fused with Fc fragment of human IgG, in which the transformants are safely delivered into intestine though oral route. Also, the invention provides a chimeric protein-expressing vector which can induce transcytosis in intestine epithelial cells. Accordingly, the invention demonstrates that the chimeric protein for oral delivery system can be absorbed in intestine, and delivery of the chimeric protein by oral route using Lactobacillus has very excellent efficiency in vivo test in rats. Accordingly, the Lactobacillus of the present invention is an excellent deliverer of protein drugs.

In vivo testing for analytes in a life-form is an attractive concept because a biological sample does not have to be removed from the life-form. However, in vivo testing alone is unable to provide information that is accurate, complete and / or reliable enough to safely replace in vitro testing. In contrast to performing either in vivo or in vitro testing independently and alone, some embodiments of the present invention provide a joint-diagnostic apparatus for combined in vivo and in vitro testing. In some specific embodiments results from an in vitro measurement module are used in combination with subsequent in vivo measurements / observations obtained at a later time, and / or vice versa. Accordingly, in some embodiments in vitro measurements are used to compliment and / or partially compensate for some of the limitations of in vivo testing, and at the same time enabling some of the benefits of in vivo testing by reducing the number of biological samples taken.

The present invention provides a method for identifying a compound or a combination of compounds having a pharmacological behavior that qualifies it as a candidate for clinical development of a drug for treatment of a psychiatric disease or disorder, preferably schizophrenia. According to this method, a candidate drug is assessed for its ability to produce a biochemical profile, in either or both in vitro and in vivo test systems, which is similar to a unique reference biochemical profile obtained following treatments with drugs or drug combinations effective against both positive and negative symptoms of psychiatric diseases or disorders.

Methods of pre-clinical animal testing to monitor physiological parameters of test animals following exposure of molecules sealed in reservoirs on implanted devices. The test molecules are exposed to physiological fluid of the animal. The molecules can be configured as a sensor chemistry that reacts with the physiological fluid. The molecules can be a drug or drug candidate that is released into the animal. The test animals are non-human mammals.

Formulations and methods for preventing, inhibiting or controlling metabolic disorder, age-related disease and acute inflammations have been developed. The compositions comprise of bilirubins, bilirubin derivatives, their tetrapyrrolic analogues, tripyrroles, and dipyrroles. The compositions can be administered as a dosage form for oral ingestion, injection, suppository, or topical application. The effective amount of the compound is typically from 0.001-100 mg / kg body weight, preferably in the range from 0.01-50 mg / kg body weight, and most preferably from 0.05-10 mg / kg body weight. Examples demonstrate the efficacy of the compounds in both in vitro and in vivo tests.

The invention belongs to the technical field of biological products and discloses a medicinal composition and application thereof. The composition takes recombinant human endostatin and hexadecadrol as effective constituents, wherein the mole ratio of the recombinant human endostatin to the hexadecadrol is 10-100:1. The recombinant human endostatin in the combination can co-act with the hexadecadrol to restrain the multiplication, invasion, migration and angiogenesis of endothelial cells. An in-vivo test result proves that the recombinant human endostatin and the hexadecadrol co-act with each other to restrain the growth of the mice H22 transplanted liver tumor and human Bel7402 transplanted liver tumor. Therefore, the composition can be widely applied to medicaments for treating liver cancer.

The invention discloses a nucleotide sequence and an amino acid sequence of a human derived membrane-stabilization mutant gene CD40L-M, and a plasmid carrier pdsAAV-CB-CD40L-M. The invention further discloses a recombinant adeno-associated virus scAAV2 / 5-Y719F-CD40L-M using CD40L-M as a target gene and highly-efficiently transducing lung cancer cells, a preparation method thereof, and an application thereof in preparing anti-cancer drugs. In vitro and in vivo tests of transduction of the CD40L-M gene into the lung cancer cells show that generation of the sCD40L is substantially reduced, a traditional AAV transduction efficiency is improved by using the recombinant adeno-associated virus scAAV2 / 5-Y719F-CD40L-M, the lung cancer cells can be highly-efficiently transduced, and the CD40L-M gene induces retardance of cell cycles, promotes cell apoptosis, induces immunization activation, inhibits growth of lung cancer in the body and reduces side effects such as liver and kidney damage.

The invention relates to a bispecific oligopeptide-lidamycin energized fusion protein Ec-LDP-Hr-AE. The fusion protein comprises two oligopeptides of targeted epidermal growth factor receptors EGFR and HER2, a lidamycin apoprotein and a lidamycin activity chromophore, and researches show that the fusion protein in vitro can be combined with the epidermal growth factor receptors EGFR and HER2 for expressing the specificities of the tumor cells, has strong damaging effect for the tumor cells and remarkable therapeutic effect for the transplanted tumor of nude mice for the ovarian cancer SK-OV-3 after the in vivo test, displays the characteristics of miniaturization and high efficiency of targeting drugs and has good application prospect.

The invention provides a lactobacillus-ginseng polysaccharide composition and its preparation method and use, and belongs to the technical field of lactobacillus compositions. The lactobacillus-ginseng polysaccharide composition comprises 4-6 parts of a lactobacillus plantarum C88 starter, 9-11 parts of ginseng extract, 28-32 parts of dried skim milk, 18-22 parts of cane sugar, 30-32 parts of dextrin, 1.6-2.4 parts of mannitol, 0.8-1.2 parts of magnesium stearate and 0.8-1.2 parts of citric acid. The lactobacillus-ginseng polysaccharide composition has good antioxidation performances which comprise removing DPPH free radical and ABTS free radical in vitro, improving vitality of antioxidant enzyme in naturally aging mouse serum and liver in an in-vivo test and reducing MDA content of naturally aging mouse serum and liver.

This invention relates to compounds with 6-aryl-3-cycloaminomethyl pyrone structure, their preparation method and their application. Pharmacological activity experiments show that the compounds have a high activity in selectively inhibiting AChE while no obvious activity in inhibiting BuChE. The activity of the compounds in inhibiting AChE is higher than huperzine A. Mouse in vivo tests show that the compounds do not have acute toxicity or abnormal reaction phenomenon, and the compounds can be used as a kind of new drugs for treating Alzheimer's disease.

The genome of the non-human mutant mammal, deficient in an endogenous Sigma receptor, contains a mutation that comprises a disruption in an endogenous Sigma rteceptor gene, wherein said gene disruption gives rise to a mutant lacking detectable levels of endogenous Sigma receptor. The mutant may be used as a control animal for in vivo tests, as well as a source of cells that can be used in in vitro tests, Mutants deficient in the Sigma-1 receptor can be used as models for in vivo study of disorders of the central nervous system, memory alterations, stress conditions and drug addictions, analgesia processes and neuroprotection. Mutants deficient in the Sigma-2 receptor can be used to study diagnostic or therapeutic tools to fight cance and / or degenerative processes and / or to design compounds capable of preventing, reducing or alleviating the secondary pathology associated with administration of neuroleptic agents.

The invention relates to the field of medicaments, in particular to a polypeptide which has the effects of inhibiting substrate metal prolease-9 and tumor necrosis factor liberase and relieving the damage of an acute inflammatory reaction on an organism. The sequence of the polypeptide is Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu which is a brand new sequence (D-Pyr is D-type pyridine alanine, D-Cys isD-type cysteine, and Bip is diphenyl alanine). The polypeptide can be used for inhibiting the activities of the substrate metal prolease-9 and the tumor necrosis factor liberase on 1 micromole level in vitro and increasing the survival rate of an endotoxic shock mouse in an in-vivo test, and has a potential new medicament development value.

The invention discloses Lactobacillus fermentum zhao capable of regulating intestinal movement and preventing constipation and application thereof, wherein the preservation number of the Lactobacillus fermentum zhao is CCTCCM2013513. The strain has higher acid resistance, has a survival rate reaching 85.12% plus / minus 5.18% after staying in pH3.0 artificial gastric juice for 3 h, can grow slowly in cholate with the concentration of 1.0% and has a growth efficiency reaching 18.33% plus / minus 0.52% of that of cholate-free culture. The hydrophobicity of Lactobacillus fermentum zhao cells is up to 70.80% plus / minus 0.61%. The Lactobacillus fermentum zhao can grow normally in human intestinal tracts. In-vivo tests using mice show that the Lactobacillus fermentum zhao can reduce the weight reduction tendency of the mice, shorten the time of defecation of dark stool, improve the peristalsis of small intestines, increase MTL, Gas, ET, AchE, SP and VIP factors to different extents, reduce SS factors, increase food consumption and water consumption, reduce the tendency that stool amount, stool pieces and stool water content decline, play an effect similar to that of a constipation medicine and show a certain constipation prevention effect.

The invention relates to a fluorescent probe capable of reversibly detecting a hypoxic environment and used in a living body environment. The fluorescent probe adopts a quinone functional group capable of performing reversible oxidation-reduction reaction in the vivo biological environment as a receptor, and uses a fluorophore of which the wave length is in a near infrared band as a signal source, and the receptor and the signal source are connected through an applicable connecting arm. In-vitro and in-vivo tests show that the probe can realize free conversion under aerobic and hypoxic conditions, and can be used in tracking of a hypoxic zone in vivo; under the hypoxic condition, fluorescent emitted by the fluorescent probe excited by laser with the wave length of 680 nm can be obviously found at a point of which the wave length is 790 nm; while under the aerobic microenvironment, the fluorescent completely disappears, so that transfer of the hypoxic zone in a body of a tumor patient can be tracked, thereby providing a judgment basis for clinical individualized administration.

A composition contains an extract of pine leaf extract or a compound isolated therefrom. It showed potent inhibitory effect on human papillomavirus (HPV) as well as anti-cancer effect on various cancer diseases through various in vitro test and in vivo tests, and therefore, it can be used as the effective and safe therapeutics or health food for treating and preventing cancer disease.

The present invention provides a method for screening for progesterone receptor isoform specific ligands as well as a first method for screening for tissue-selective progesterone receptor ligands, both methods comprising selecting progesterone receptor isoform A or progesterone receptor isoform B selective ligands by means of an assay involving cells stably transfected with plasmids expressing the progesterone receptor isoform A or B. Furthermore, the present invention provides a second method for screening for tissue-selective progesterone receptor ligands, comprising in vivo tests in desired target tissues. The present invention further relates to cell lines suitable for this transactivation assay, a respective assay kit and medical uses of the isoform-specific and / or tissue-selective progesterone receptor ligands according to the present invention.

The invention relates to application of natural compound ursolic acid on antibiosis, in particular to application of the combination of the natural compound ursolic acid and penicillin on resisting drug resistant staphylococcus aureus. The compound ursolic acid is widely distributed in nature, so that the material source is wide. Aiming at the serious problem of the drug resistance of the staphylococcus aureus at present, the in vitro and in vivo antibiotic tests are carried out for the ursolic acid. Particularly the in vitro synergic test proves that the ursolic acid has better antibacterial activity on the drug resistant staphylococcus aureus under the combination action of the ursolic acid and the penicillin, and the lowest bacteriostatic concentration is 1.13 mu g / disc; moreover, the in vivo test also shows that the ursolic acid has better activity under the synergic action.

The invention discloses HLA-A2 restrictive epitope polypeptide of an LMP2A protein source, which is polypeptide LMP2A264 and comprises 9 amino acids in the positions of 264 to 272; the sequence is QLSPLLGAV. Mycobacteria heat shock protein 70 (HSP70) is expressed, identified and purified; a transgene animal model for evaluating EBV relevant polypeptide vaccine in vivo tests is established; the immune research on inducing EBV specific CTL inside and outside healthy volunteers and transgene rats for the new EBV epitope polypeptide LMP2A264 is systemically researched and the tumor prevention andthe tumor treating test of the polypeptide LMP2A264 on LMP2A positive solid tumors are evaluated, thereby proving that the polypeptide LMP2A264 can induce LMP2A specific cell toxic T lymphocyte reaction. Therefore, the polypeptide LMP2A264 can be applied to prepare medicaments for treating or preventing LMP2A positive solid tumors.

The invention discloses a series of urea transporter inhibitors of which the structural formula is disclosed in the specification. An erythrocyte model is used for screening to obtain compounds for inhibiting urea transporters. The experimental result indicates that the compounds (such as Youti) can inhibit the permeation of urea transporter UT-B mediated erythrocyte membranes for urea, and the action forms a dosage dependency relationship; Youti within effective dose range has no cytotoxic action on the MDCK (Madin-Darby Canine Kidney) cells, which indicates that the action of Youti for inhibiting cell permeable urea is irrelevant to cytotoxicity; the inhibiting action of Youti on the urea transporter UT-B gradually increases; the inhibiting action of Youti on the urea transporter UT-B is reversible; and the in-vivo test result proves that Youti can obviously increase the uresis amount of a rat, lower the concentration of urea in the urine of the rat, and lower the osmotic pressure, which indicates that Youti has selective diuresis action on urea in vivo.

The invention relates to the field of drugs and in particular relates to polypeptides capable of inhibiting matrix metalloproteinase-2 and tumor necrosis factor liberase and also capable of relieving damage of acute inflammatory reaction to an organism. The sequence of the polypeptides is Trp-Ser-Asn-Val-Gly-Gly-Gly-Gly-Glu-Lys-Met, which is a brand new sequence; the polypeptides are capable of inhibiting the activities of matrix metalloproteinase-2 and the tumor necrosis factor liberase in vitro on the level of 1 micromole, and also capable of increasing the survival rate of endotoxic shock mice in in vivo tests; the polypeptides have potential new drug development value.