68 results about "Treating tuberculosis" patented technology

The invention discloses identification and application of a mycobacterium tuberculosis bacteriophage susceptibility gene, and a gene target which affects mycobacterium bacteriophage infection efficiency is obtained through combined application of a mycobacterium tuberculosis CRISPR-KO library and a CRISPRi library and bacteriophage D29 infection screening. Reagents or drugs targeting phage susceptibility genes or encoded proteins thereof are screened based on the gene targets, and the reagents or drugs can knock out the phage susceptibility genes or inhibit expression of the phage susceptibility genes, or inhibit activity of the encoded proteins of the phage susceptibility genes, serve as phage synergists, or are combined with antibiotics to be used with phages, and can be used for preparing drugs for treating the phage susceptibility genes or the encoded proteins of the phage susceptibility genes. The bacteriophage-antibiotic composition has the advantages that a synergistic sterilization effect is achieved, a new strategy is provided for bacteriophage-antibiotic combined treatment of drug-resistant mycobacterium infection, rapid sterilization is expected to be achieved, the treatment course is shortened, and finally the target of rapid treatment of tuberculosis and other pathogenic mycobacterium infection is achieved.

The invention relates to the technical field of biological medicines, in particular to a tuberculosis vaccine antigen and a vaccine. In particular to application of a mycobacterium tuberculosis Rv1787 gene in preparation of a vaccine for preventing and / or treating tuberculosis, in the application, the sequence of the Rv1787 gene or an encoding product thereof is defined, and the Rv1787 gene and the encoding product thereof serve as antigens, have mycobacterium tuberculosis specificity, and can be used for preparing a vaccine for preventing and / or treating tuberculosis. According to the mycobacterium tuberculosis vaccine, identification and response of an organism immune system to mycobacterium tuberculosis can be accurately stimulated, non-specific immune response to other normal tissues is avoided, a brand new and specific molecular target spot is provided for preventing and treating tuberculosis, and the limitation that a traditional vaccine depends on a single antigen or an attenuated strain is broken through. A specific expression product of the gene can stimulate directional recognition and attack of an organism immune system on mycobacterium tuberculosis, the pertinence and effectiveness of vaccines are remarkably improved, and a new path is provided for solving the problem of tuberculosis prevention and treatment.

The invention relates to a 6, 5, 7, 6-tetracyclic derivative with a structural characteristic shown in a formula (I) as well as a preparation method and application of the 6, 5, 7, 6-tetracyclic derivative, including application of pharmaceutically acceptable salt of the 6, 5, 7, 6-tetracyclic derivative in treatment of tuberculosis. The compound is novel in structure, has good in-vitro and in-vivo anti-tubercle bacillus activity, and is a novel anti-tubercle bacillus compound with a good application prospect in the field of medicines. # imgabs0 #

Disclosed are an mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one early-secreted antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof; PE / PPE family antigen WAG22 of Mycobacterium tuberculosis or an immunologically active fragment thereof; and at least one latent-related antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which may serve as a prophylactic vaccine for preventing latent activation or as a therapeutic drug for treating active tuberculosis, exhibiting a significant inhibitory effect on Mycobacterium tuberculosis.

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; a mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunocompetence fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

Disclosed are compositions and methods for the treatment of tuberculosis and other mycobacterial and gram-positive bacterial infections. These compositions comprise highly potent and selective oxazolidinones encapsulated with high efficiency to maximize the potential for low-toxicity drug delivery and are stable in the presence of plasma. The compositions are long-circulating and retain their encapsulated drug while in circulation following intravenous delivery to allow effective accumulation at the site of bacterial or mycobacterial infection. The high doses achievable and the long-circulating nature of the drug combined with the high stability of the formulation allow for a reduction in the frequency of administration compared to the once-daily or twice-daily administration of other drugs commonly used to treat these infections.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting BCG (bacillus calmette guerin) BCG3965 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 3-5; and the light chain variable region CDR sequences are as shown in SEQ ID NO: 7-9. The monoclonal antibody 5F10 shows efficient antituberculous activity in vivo and in vitro through specific targeting of BCG3965 protein on the surface of mycobacterium tuberculosis, mainly including the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 5F10 is clear in sequence and structure, easy to develop and modify, and capable of being used for preparing antituberculous drugs for treating mycobacterium tuberculosis. The monoclonal antibody 5F10 disclosed by the invention has the advantages that the monoclonal antibody 5F10 is not easy to induce pathogens to generate drug resistance by an immune-mediated treatment mechanism, and the monoclonal antibody 5F10 is applied to prevention and treatment of tuberculosis, not only provides a new choice for treatment of tuberculosis, but also provides an important technical basis for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and is wide in application prospect.

Methods for treating tuberculosis are provided.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting mycobacterium tuberculosis MPT83 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 5-7; cDR sequences of a light chain variable region are as follows: SEQ ID NO: 9-10 and LAS. The monoclonal antibody 9C9 can be specifically combined with MPT83 protein on the surface of Mycobacterium tuberculosis (MTB) and shows efficient antituberculous activity in vivo and in vitro, the activity mainly comprises the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 9C9 is clear in sequence and structure, easy to develop and modify and capable of being used for preparing the anti-tubercle bacillus monoclonal antibody 9C9. The monoclonal antibody 9C9 disclosed by the invention has the advantages that the monoclonal antibody 9C9 can be used for preventing and treating tuberculosis, an immune-mediated treatment mechanism of the monoclonal antibody 9C9 does not easily induce pathogens to generate drug resistance, a new choice is provided for the treatment of tuberculosis when the monoclonal antibody 9C9 is applied to prevention and treatment of tuberculosis, an important technical basis is also provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The invention provides a composition (e.g., pharmaceutical composition) comprising a combination of two or more phages, wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The invention provides a method of treating, reducing, or preventing a disease caused by Mycobacterium tuberculosis in a mammal comprising administering a pharmaceutical composition comprising a combination of two or more phages wherein the phages are two or more of: (a) phage D29; (b) phage AdephagiaΔ41Δ43; (c) phage FionnbharthΔ47; (d) phage Fred313cpm-1; and (e) phage MuddyHRMN0052-1; and a pharmaceutically acceptable carrier. The composition can be administered alone or in combination with one or more antibiotics, wherein the length of treatment is reduced as compared to the length of treatment with one or more antibiotics alone.

The present disclosure provides small molecule anti-tuberculosis agents and pharmaceutical compositions comprising the anti-tuberculosis agents. The disclosure further provides a method of treating tuberculosis, including drug-resistant tuberculosis, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the anti-tuberculosis agent.

The invention concerns a compound of formula (Ia) or (Ib) wherein R1 is hydrogen or a methyl group; R2 is an unsubsti- tuted or substituted alkyl group; R3 is an aryl group or a heteroaryl group, optionally substituted by one or more groups selected from halogen, alkyl or alkoxy; and, in Formula (Ia), X is CH or N and Y is NH, S or O, or, in Formula (Ib), X is NH, S or O and Y is CH or N. The invention further concerns a method of synthesiz- ing the inventive compound, a composition comprising the inven- tive compound or a pharmaceutically acceptable salt thereof and bedaquiline (BDQ), an analogue of bedaquiline (BDQ) or a mix- ture thereof, and the use of said composition or compound for the treatment of tuberculosis.

The present invention relates to a compound having the formula (Ia) or (Ib) wherein R1 is hydrogen or methyl; R2 is unsubstituted or substituted alkyl; R3 is aryl or heteroaryl, which is optionally substituted by one or more groups selected from halogen, alkyl or alkoxy; and, in formula (Ia), X is CH or N and Y is NH, S or O, or in formula (Ib), X is NH, S or O and Y is CH or N. The present invention further relates to a method for synthesizing the compounds of the present invention, a composition comprising a compound of the present invention or a pharmaceutically acceptable salt thereof and bedaquiline (BDQ), an analogue of bedaquiline (BDQ) or a mixture thereof, and the use of said composition or compound for the treatment of tuberculosis.

The invention belongs to the technical field of bioengineering, and particularly provides application of a JNK inhibitor in preparation of drugs for preventing and / or relieving and / or treating pulmonary tuberculosis aiming at the problem that whether the existing JNK inhibitor SP600125 can inhibit BNIP3-mediated mitochondrial autophagy and further exert the ROS bactericidal effect is unknown. And the JNK inhibitor is an SP600125 JNK inhibitor. The JNK inhibitor is used for inhibiting mitochondrial autophagy in the BCG infected macrophages. The JNK inhibitor reduces the up-regulation of BNIP3 and LC3B caused by BCG infection. It is found through the application that when the concentration of the JNK inhibitor reaches 15 umol / L, remarkable cytotoxicity begins to appear, and compared with a control group, the cell survival rate is remarkably decreased. The SP600125 can be used for inhibiting mitochondrial autophagy and down-regulating the expression of BNIP3 and LC3B. Inhibition of JNK expression can inhibit survival of Mtb in RAW264.7 macrophages, and a new thought and direction are provided for treatment of tuberculosis.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting Mycobacterium tuberculosis PspA and a preparation method and application thereof, the protective monoclonal antibody comprises at least one of the following CDR sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 4-6; the light chain variable region CDR sequences are as shown in SEQ ID NO: 8-9 and WAS. The antibody or the antigen binding fragment can specifically bind to PspA protein of mycobacterium tuberculosis (MTB), shows efficient antituberculous activity in vivo and in vitro, specifically, can significantly enhance phagocytosis of macrophages on tubercle bacillus, inhibit tubercle bacillus growth and the like, and is clear in sequence and structure, so that the antibody or the antigen binding fragment is easy to develop and transform, and has broad application prospects. And moreover, an immune-mediated treatment mechanism is not easy to induce pathogens to generate drug resistance, so that when being applied to prevention and treatment of tuberculosis, not only is a new choice provided for treatment of tuberculosis, but also an important basis is provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The invention belongs to the technical field of biological medicines, and particularly discloses an application of L-citrulline (L-citrulline, Cit) in preparation of a medicine for preventing or treating tuberculosis. The invention provides application of L-citrulline in preparation of medicines for preventing or treating tuberculosis. The invention provides a medicine for preventing or treating tuberculosis. The medicine comprises L-citrulline. The invention discloses application of L-citrulline in preparation of drugs for preventing or treating tuberculosis, the L-citrulline can significantly reduce the bacterial load after mycobacterium marinum infection and prolong the survival time of zebra fish, and the L-citrulline has the prospect of being developed into related drugs for preventing and treating tuberculosis.

Provided is use of an endoperoxide in preparing an anti-microbial drug. In an anoxic condition, the endoperoxide can partially and effectively inhibit the survival of Mycobacterium tuberculosis. Provided is use of an endoperoxide in combination with a respiratory chain inhibitor in preparing an anti-microbial drug. The endoperoxide includes artemisinin and derivatives thereof, and other endoperoxides with a two-oxygen bridge structure. The endoperoxide has synergistic effects with a variety of respiratory chain inhibitors, and the combination has a more effective inhibition effect on Mycobacterium tuberculosis.

The application discloses a mycobacterium tuberculosis tandem DNA vaccine W545 and a preparation method and application thereof. The application constructs a novel mycobacterium tuberculosis DNA vaccine W545 with a multi-antigen immune dominant epitope by connecting epitope genes of Ag85A protein and Ag85B protein antigen and Rv1419, Rv3407 and Rv2628c together in series through genetic engineering technology and connecting the epitope genes to a eukaryotic expression vector pVAX1. The prepared mycobacterium tuberculosis tandem DNA vaccine W545 can significantly enhance specific cellular immune function of mice, mainly stimulates Th1 type immune response, and can make the lesion range of organs and tissues of a mouse tuberculosis model significantly reduced and the lesion alleviated in treatment, and can be used in preparation of drugs or vaccines for preventing or treating tuberculosis.

The present invention provides cytochrome bd oxidase inhibitors. The present invention provides the use of the cytochrome bd oxidase inhibitors as a medicament to treat a bacterial infection. The present invention also provides the use of the cytochrome bd oxidase inhibitors as a medicament to treat a bacterial infection with a QcrB inhibitor.

A human antibody comprising an antigen binding domain which binds PstS1 of Mycobacterium tuberculosis (TB) for use in preventing or treating TB infection in a subject in need thereof is provided. Also provided are vaccine compositions and conjugates of such antibodies.

The present disclosure provides agents and methods for preventing or treating tuberculosis using RNA. The RNA encoding variants of antigens of Mycobacterium tuberculosis ox of fragments thereof is formulated and administered in a way that the variants are produced by cells of a subject, in particular after intramuscular or intravenous administration of the RNA.

The invention relates to a compound for preventing or treating tuberculosis (TB) or an acceptable salt of the compound, and the compound is shown as a general formula (I).

The present disclosure provides agents and methods for preventing or treating tuberculosis using RNA. The RNA encoding variants of antigens of Mycobacterium tuberculosis ox of fragments thereof is formulated and administered in a way that the variants are produced by cells of a subject, in particular after intramuscular or intravenous administration of the RNA.

The present invention discloses compounds according to Formula (I) wherein X, L1, R1 and Cy are as defined herein. Herein are disclosed compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and / or treatment of diseases involving tuberculosis (TB) and / or non-tuberculous mycobacteria (NTM).

An mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; Mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

Provided is a compound for preventing or treating tuberculosis (TB) or an acceptable salt thereof, the compound being represented by general formula (I).

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

The present invention relates to compounds of formula (IA): including any stereochemically isomeric form thereof or a pharmaceutically acceptable salt thereof for use in the treatment of tuberculosis.

An mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

A chrysin derivative and a composition for a treatment of tuberculosis containing the same are provided. In detail, a chrysin derivative compound represented by chemical formula 1,or a salt thereof, and a composition for a treatment of tuberculosis and inflammation containing the same as an active ingredient are provided. In chemical formula 1, at least one of R1 and R2 is hydrogen, and the other is a C1-6 hydroxyalkyl group or a C1-10 alkenyl group unsubstituted or substituted with one or more C1-10 alkyl groups