55 results about "Clostridium difficile infections" patented technology

The invention discloses a probiotic-polyphenol nanoparticle colon-targeted co-delivery system as well as a preparation method and application thereof, and belongs to the field of biological medicines. The FCPs and hyaluronic acid (HA) are combined through non-covalent interaction, so that the hydrogel has colon targeting property and mucosal adhesion at the same time, and delivery of probiotics is facilitated. The hydrogel (HF) based on polysaccharide has good biocompatibility, and can be used for effectively encapsulating the probiotics and the natural products. Then, the PDA-TH NPs and BA are incorporated into the polysaccharide chain network of HF, and finally the BA-HF-PDAT targeted co-delivery system is constructed. The BA (at) HF-PDAT targeted co-delivery system can protect BA from serious gastrointestinal stress, and is jointly assembled with PDT-TH NPs to realize dual slow release of thymol (Thy), so that the treatment effect of BA and Thy is improved, and the BA (at) HF-PDAT targeted co-delivery system contributes to treatment of clostridium difficile infection (CDI).

Provided are methods and compositions for treating and / or preventing C. difficile infections, particularly recurring C. difficile infections. The compositions for use in treating and / or preventing C. difficile infections include in some embodiments at least one agent that inhibits an alpha 2 adrenergic receptor, and the presently disclosed methods include administering at least one such composition to a subject in need thereof, optionally in combination with other therapeutically active agents including but not limited to an enhancer of an IL-13 biological activity, optionally an IL-13 peptide or a fragment or homolog thereof; an interleukin-13 receptor subunit alpha-2 (IL-13Ra2) inhibitor; an enhancer of an Interleukin-33 (IL-33) biological activity, optionally an IL-33 polypeptide or a biologically active fragment or homolog thereof; or any combination thereof.

The invention provides a clostridium difficile infection and recurrent infection prediction model construction system, a storage medium and a kit, and the method comprises the steps: collecting an excrement sample of a Crohn disease subject through a collection module, and obtaining the genus-level relative abundance information of a flora genus level; the feature selection module adopts an LEfSe and Lasso feature screening algorithm to screen out a feature bacterial genus set; the training module is used for training prediction models by using an ElasticNet method based on genus-level relative abundance information of the characteristic bacterial genus set; the identification module obtains genus-level relative abundance information of a characteristic bacterium genus set of an individual to be tested and inputs the genus-level relative abundance information into the trained prediction model to obtain a risk score, and the prediction ability shows excellent sensitivity, specificity and accuracy in a training set and an independent test set.

Disclosed herein are methods for administering a dose of a microbiota recovery therapy composition by colonoscopy. The methods disclosed herein are useful for the treatment of diseases and / or conditions of the digestive tract, such as Clostridium difficile infection (GDI), including recurrent GDI, and other gastrointestinal disorders. The method can result in improved quality of life. These methods are capable of altering the gut microbiota composition and / or the gut metabolome composition. The microbiota recovery therapy composition comprises a fecal microbiota suspension comprising: a fecal microorganism derived from a human fecal sample, and a solution of polyethylene glycol and brine.

The present invention relates to methods and compositions for reducing the risk and severity of C. difficile infection. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacterium Clostridium scindens, contributes substantially to resistance against C. difficile infection. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids.

Provided herein are methods for treating or preventing recurrent Clostridioides difficile infection, comprising bacterial strains belonging to species Clostridium bolteae, Anaerotruncus colihominis, and / or Flavonifractor plautii. Also provided are compositions comprising bacterial mixtures of strains including Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiostim, Blautia producta, Dorea longicatena, Clostridium innocuum, Flavonifractor plautii, Lachnospiraceae bacterium, and / or Bifidobacterium longum. Also provided are methods of using compositions comprising such bacterial mixtures (e.g., for treating or preventing Clostridium difficile infection).

Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventing Clostridium difficile infections using the engineered strains of yeast. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and / or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.

The present application provides the use of a nanocomposite with a core-shell structure. Specifically, the present application provides the use of a nanocomposite with a core-shell structure in the preparation of a drug for preventing and / or treating Clostridium difficile infection and recurrent diseases caused thereby, wherein the nanocomposite comprises: ZnO nanoparticles as a core; mesoporous silica as a shell coated on the surface of the ZnO nanoparticles; an antibiotic loaded in the pore channel of the mesoporous silica; hyperbranched polylysine modified on the surface of the mesoporous silica; and a pH-responsive coating material as the outermost layer. The nanocomposite provided by the present application can achieve precise targeted release of the drug in the colon, and through the sequential and synergistic mechanism of "membrane breaking-sterilization-spore inhibition-repair", it can simultaneously solve multiple factors leading to CDI recurrence such as biofilm protection, spore storage, bacterial population destruction, mucosal damage, etc., and improve the treatment effect.

The invention relates to the field of bacteriostasis of clostridium difficile, in particular to bacillus coagulans, clostridium butyricum, a combination of the bacillus coagulans and the clostridium butyricum and application of the bacillus coagulans and the clostridium butyricum in relieving clostridium difficile infection. The bacillus coagulans is bacillus coagulans BC99 of which the preservation number is CGMCC (China General Microbiological Culture Collection Center) NO. 21801, and the bacillus coagulans BC99 is a bacillus coagulans BC99 of which the preservation number is CGMCC NO. The clostridium butyricum is a clostridium butyricum CB39 with the preservation number of CGMCC (China General Microbiological Culture Collection Center) NO. 33734, and the clostridium butyricum is a clostridium butyricum CB39 with the preservation number of CGMCC NO. The invention discloses inhibition effects of the bacillus coagulans, the clostridium butyricum and the combination thereof on clostridium difficile, and regulation and improvement of intestinal infection caused by the clostridium difficile.

The present invention provides a circular DNA template precursor for detecting Clostridium difficile, a preparation method thereof and an application thereof. The circular DNA template precursor includes a three-dimensional self-assembly reaction using a reaction system composed of H1 and H2 hairpin probes and a trigger strand Trigger. The three-dimensional self-assembly reaction includes Trigger triggering the H1 hairpin structure to form a T / H1 intermediate, the H1 hairpin structure being unfolded and binding to H2 to produce an H1 / H2 structure, and the DNA template of H2 being cyclized to obtain the circular DNA template precursor. When Clostridium difficile toxin is present, the trigger strand Trigger can be released again, and can continuously catalyze the hairpin structure of the H1 DNA hairpin probe without being consumed. By adopting the technical scheme of the present invention, signal cascade three-stage amplification is realized through three-dimensional self-assembly-amplification reaction and silver-enhanced gold nanoparticles, so as to realize highly sensitive and highly specific detection of Clostridium difficile infection.

The invention belongs to the technical field of chemical drugs, and particularly relates to application of a traditional Chinese medicine composition in preparation of drugs for treating recurrent clostridium difficile infection.The traditional Chinese medicine composition is prepared from 10-50 g of fresh ginger, 3-20 g of honey-fried licorice roots, 5-30 g of ginseng, 3-20 g of dried ginger, 3-30 g of scutellaria baicalensis, 3-30 g of pinellia ternate, 3-15 g of coptis chinensis and 10-30 g of Chinese dates. The traditional Chinese medicine composition is excellent in clinical effect, and in sample research on high-risk crowds such as old people and immunosuppression CDI relapse patients, the treatment scheme of the vancomycin combined with the ginger heart-fire purging decoction is remarkably superior to vancomycin single-drug treatment in the aspect of continuous clinical response rate at the main curative effect end point. This benefit is achieved mainly by reducing the recurrence rate of CDI by more than 60%. The combined scheme shows a robust curative effect in key subgroups such as the elderly and immunosuppressive subgroups, is good in safety, does not increase extra adverse event risks, and particularly does not observe renal function impairment.

A piezoelectric plate sensor comprising a piezoelectric layer; two electrodes; and an insulation layer. The insulation layer is produced by soaking the piezoelectric layer and two electrodes in a mercaptopropyltrimethoxysilane solution with an amount of water from 0.1 v / v. % to about 1 v / v % and at pH from about 8 to about 150 for a period from about 8 to about 15 hours, and the mercaptopropyltrimethoxysilane solution has a concentration of mercaptopropyltrimethoxysilane from about 0.01 v / v % to about 0.5 v / v %. A method of detecting a biomolecule in a sample using the piezoelectric plate sensor in particular, that of detecting a genetic marker with PCR sensitivity and specificity without the need of DNA isolation or amplification is also provided. The piezoelectric plate sensor may be used to diagnose various diseases including breast cancer, myocardial infarction, diarrhea, Clostridium difficile infection, and hepatitis B infection.

The present invention relates to immunogenic compositions that comprise a Clostridioides difficile toxoid A and / or a C. difficile toxoid B, and an adjuvant, and methods of use thereof. The present invention further relates to methods for eliciting an enhanced immune response in a human against a C. difficile infection. The methods include administering to the human an effective dose of an immunogenic composition, which includes a C. difficile toxoid and an adjuvant, wherein the composition is administered two or three times.

The present invention relates to methods and compositions for reducing the risk and severity of C. difficile infection. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacterium Clostridium scindens, contributes substantially to resistance against C. difficile infection. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids.

In an embodiment, the present disclosure pertains to a method of treating or preventing C. difficile infections. In some embodiments, the method includes administering an anti-toxin to a subject in need thereof. In some embodiments, the anti-toxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an anti-toxin for treating or preventing C. difficile infections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization of Clostridium difficile toxin B (TcdB).

To provide new and / or alternative therapeutic solutions which may alleviate the symptoms associated with Clostridium difficile infection, preferably intestinal infections, and / or cure the physiopathological conditions related to / associated therewith.SOLUTION: The present invention relates to the use of specific strains of Lactobacillus paracasei or of a composition comprising the strains for the prevention and / or treatment of a physiopathological condition related to / associated with Clostridium difficile infection, preferably intestinal infections, or so-called CD-associated disease (CDAD) or CD infection (CDI).SELECTED DRAWING: None

The invention discloses a microbial marker for treating recurrent clostridium difficile infection based on coprophilous fungus transplantation and a screening method of the microbial marker. The microbial marker comprises the following components: Dorea longigena, Alistipes putredinis, Citrobacter farmeri, Coprococcos, Eubacter coprostanoliganes, Agatrobacter rectas, Dorea foetida, Blauria obbe, Klebsiella foetida, Blauria foetida, Blauria ovaticus and Gemmigerformation. The microbial marker comprises the following components: Dorea longigena, Alistipes putredinis, Citrobacter farmeri, Citrobacter coprostanoliganes, Citrobacter rectas, according to the invention, through metagenome sequencing and a machine learning algorithm, key microbial markers significantly related to recurrent clostridium difficile symptom improvement in the coprophilous fungus transplantation treatment process are screened out, and a scientific basis and a standardized scheme are provided for coprophilous fungus transplantation treatment of recurrent clostridium difficile infection.

The present invention belongs to the field of feed technology, and discloses a high-iron feed for preventing and treating Clostridium difficile infection in mice and its application. The raw material composition of the high-iron feed is as follows in g / kg: casein 200, L-cystine 3, corn starch 397.5, maltodextrin 132, sucrose 100, cellulose 50, soybean oil 70, mixed vitamins 10, mixed minerals 35, and ferrous sulfate 0.4. The high-iron feed can be used as a dietary intervention for intestinal inflammation caused by Clostridium difficile infection in mice. Through animal experiments, it was found that the high-iron feed can effectively inhibit the colonization and germination of Clostridium difficile spores in mice, alleviate clinical symptoms such as weight loss, diarrhea, and hunchback caused by Clostridium difficile infection, increase the secretion of beneficial compounds such as tauroursodeoxycholic acid and trillium glycosides, reduce the production of inflammatory cells and inflammatory factors, and thus alleviate Clostridium difficile infectious enteritis. It provides important experimental data for the development of non-antibiotic therapy for Clostridium difficile, and has good application prospects and huge potential value.

An insoluble cell fraction obtained from plant cells cultured in a suspension composed entirely of natural molecules for the treatment of primary and recurrent Clostridium difficile infections is provided. A process for the preparation of the insoluble cell fraction is also provided.

The present invention relates to a recombinant endolysin for controlling Clostridioides difficile infectious disease, and a use thereof, and, more specifically, to endolysin PHICD111_20024_EAD having excellent salt stability, and a use thereof. The endolysin PHICD111_20024_EAD, newly isolated in the present invention, exhibits specific activity against Clostridioides difficile, which is one of the causative bacteria of intestinal inflammation, and strains belonging to the genus Bacillus and Listeria monocytogenes, which are known as causative bacteria of food poisoning. The endolysin PHICD111_20024_EAD of the present invention does not affect humans and animals, and thus is safe and applicable to the pharmaceutical industry, food industry, biotechnology and the like, and also can effectively kill bacteria at a target site or target substance without problems related to antibacterial resistance.

The invention discloses a traditional Chinese medicine plaster for adjuvant therapy of clostridium difficile infection and reconstruction of intestinal flora balance and a preparation method thereof, and relates to the technical field of traditional Chinese medicine plasters, the traditional Chinese medicine plaster comprises a base material layer, an ointment and a protective layer, the ointment is prepared from effective components, a penetrant, an excipient, an adsorbent and deionized water; the effective components are prepared from rhizoma atractylodis macrocephalae volatile oil, cortex magnoliae officinalis volatile oil, folium artemisiae argyi volatile oil, a rhizoma coptidis extract, a herba taraxaci extract, a radix paeoniae alba extract and a poria cocos extract; according to the present invention, the accurate intervention of the intestinal microenvironment is achieved through the umbilical region targeting drug delivery and the combination of the dual mechanisms of the transdermal absorption and the acupoint stimulation, the drug action time is prolonged through the adsorbent porous slow-release structure, the flora balance is synchronously adjusted, the pathogenic bacterium proliferation is inhibited, and the limitation of the traditional oral administration or injection therapy is broken through; an efficient and convenient traditional Chinese medicine external treatment solution is provided for the drug-resistant clostridium difficile infection.

Aspects herein concern cdtR mutations that can lead to reduced or absent virulence in C. difficile bacteria. Disclosed are compositions and methods using the cdtR mutants to treat or prevent C. difficile infections or diseases caused by C. difficile. Also disclosed are methods for detecting or determining C. difficile virulence based on mutation status of the cdtR gene in C. difficile.

The construction method comprises the following steps: amplifying a Cwp8 protein gene on a clostridium difficile genome, constructing the Cwp8 protein gene on a pLEB124 plasmid to obtain a recombinant plasmid pLEB124-Cwp8, and transferring the recombinant plasmid pLEB124-Cwp8 into lactococcus lactis F44 to obtain the clostridium difficile resistant lactococcus lactis, which is named as Lla-Cwp8, and the clostridium difficile resistant lactococcus lactis is named as Lla-Cwp8, and the clostridium difficile resistant lactococcus lactis is named as Lla-Cwp8. The surface of the Lla-Cwp8 disclosed by the invention can express the adhesion protein and realize high yield of Nisin. Experiments prove that Lla-Cwp8 has strong competition, rejection and translocation capabilities on clostridium difficile in vitro, can effectively reduce the survival rate of clostridium difficile and reduce colon shortening in vivo, can significantly reduce the expression of virulence proteins TcdA and TcdB and the expression of immune factors TNF-alpha and IL-6, and has a treatment effect on clostridium difficile infection.

The invention discloses a lactobacillus rhamnosus A21174 for inhibiting infection of multiple drug-resistant strains and clostridium difficile and application of the lactobacillus rhamnosus A21174. The lactobacillus rhamnosus A21174 has an obvious inhibiting effect on drug-resistant staphylococcus aureus, pseudomonas aeruginosa, drug-resistant escherichia coli, drug-resistant acinetobacter baumannii and clostridium difficile type strains. Compared with a commercial strain # imgabs0 # lactobacillus rhamnosus, the lactobacillus rhamnosus A21173 disclosed by the invention has a better antibacterial effect on clostridium difficile. The lactobacillus rhamnosus A21174 also shows good effects in in-vivo and in-vitro experiments such as artificial gastrointestinal fluid resistance, cholate resistance, aging resistance, life prolonging, oxidation resistance, cognition improvement and the like, so that the strain can be used as a probiotic agent for preparing a product for regulating intestinal flora, and has a good application prospect. The invention has important significance for preventing and / or treating diseases caused by multidrug-resistant bacterium infection, clostridium difficile and pseudomonas aeruginosa infection.

The invention relates to the technical field of biosensing and medical instruments, in particular to an organic electrochemical transistor sensor and a preparation method and application thereof. According to the specific technical scheme, the surface of a grid electrode is sequentially modified with a mercaptoacetic acid self-assembly layer, an anti-clostridium difficile toxin B (TcdB) antibody (such as E3), ethanolamine and bovine serum albumin (BSA), and a biological function interface with high specific recognition and strong non-specific adsorption resistance is constructed. The preparation method is simple and stable. The obtained sensor has extremely high detection sensitivity (fg / mL level), good selectivity and a wide linear range on TcdB, can complete detection within a few minutes, is particularly suitable for rapid and accurate detection of TcdB in a complex biological sample, and has a wide application prospect in the field of bedside diagnosis of clostridium difficile infection.

The present invention provides a prediction model construction system, storage medium and kit for the occurrence of Clostridium difficile infection and recurrent infection. The collection module collects fecal samples from Crohn's disease subjects to obtain genus-level relative abundance information at the genus level of the bacterial flora; the feature selection module uses LEfSe and Lasso feature screening algorithms to screen out characteristic bacterial genus sets; the training module uses the ElasticNet method to train the prediction models based on the genus-level relative abundance information of the characteristic bacterial genus sets; the recognition module obtains the genus-level relative abundance information of the characteristic bacterial genus sets of the individual to be tested, and inputs the trained prediction model to obtain a risk score. The prediction ability shows excellent sensitivity, specificity and accuracy in both the training set and the independent test set.

The invention discloses an intestinal flora preparation based on polylactic acid microspheres and a preparation method of the intestinal flora preparation, and belongs to the technical field of biological medicines.The preparation comprises functional active flora and the polylactic acid microspheres loaded with the flora, the screened and extracted functional intestinal flora is combined with the biodegradable polylactic acid microspheres, and the functional active flora and the polylactic acid microspheres are combined to prepare the intestinal flora preparation based on the polylactic acid microspheres. The sustained release characteristic, adhesion and protection effect of the polylactic acid microspheres are utilized, the colonization rate, survival rate and durability of transplanted flora in the intestinal tract of a host are remarkably improved, and the preparation can be used for preparing drugs for treating related diseases caused by alteration of intestinal flora, such as clostridium difficile infection, inflammatory bowel disease, metabolic syndrome, autism and the like, and can be used for preparing medicines for treating related diseases caused by alteration of intestinal flora. The composition has the advantages of remarkable curative effect, good stability, convenience in use and the like.