79 results about "Levodopa" patented technology

The invention discloses a recombinant escherichia coli engineering strain for producing levodopa and application, and belongs to the technical field of genetic engineering and bioengineering. Escherichia coli WSH-Z06 is used as a starting strain, a levodopa synthesis route is constructed, and supply of cofactors is enhanced by introducing glucose dehydrogenase BmgdH; and the catalytic efficiency of the HpaB is greatly improved by modifying the entrance of the HpaB substrate tunnel. In addition, by optimizing the fermentation pH and induction time, the accumulation amount of the levodopa in the fermentation liquor reaches 60.7 g / L, the production intensity reaches 1.26 g / L / h, a foundation is laid for industrial production of the levodopa, and potential value and significance are achieved for development of synthetic biology.

The invention is a method for treating levodopa naïve patients with Parkinson's disease by orally administering a controlled release levodopa formulation twice a day to the levodopa naïve patient and the method provides an improvement of a patient's motor state as determined by patient's Parkinson's disease diary, provides a reduction of from about 10%-40% in the patient's tremor, dyskinesia, and / or mobility and / or provides a reduction in the patient's Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores by at least 3 points.

The present invention generally provides methods and compositions for the treatment of Parkinson's disease and depression and / or anxiety. The invention relates to recombinant microorganisms, particularly gut-colonizing probiotics, modified to produce L-DOPA.

The present disclosure relates to compounds of formula (I) that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.

The invention belongs to the technical field of biological medicines, and particularly relates to nasal temperature-sensitive hydrogel with immunoregulation and anti-inflammatory functions as well as a preparation method and application of the nasal temperature-sensitive hydrogel. The preparation method of the nasal temperature-sensitive hydrogel with the immunoregulation and anti-inflammatory functions comprises the following steps: preparation of hydroxybutyl chitosan (HBC), preparation of levodopa-hydroxybutyl chitosan (LHBC), and preparation of CELHBC composite hydrogel. The novel temperature-sensitive hydrogel composite material of the composite hydrogel loaded with the chlorella / exosome can be used for the focus position of allergic rhinitis, and enrichment and retention of active ingredients are achieved; the chlorella is combined with the exosome, so that the inflammatory response of nasal mucosa can be relieved, the damaged nasal mucosa can be repaired, and the immune imbalance of Th1 / Th2 cells can be reversed, thereby improving the treatment effect of allergic rhinitis.

The invention relates to a polypeptide derivative for pancreas islet surface modification and inhibition of pancreas islet transplantation IBMIR reaction, and belongs to the technical field of biological medicine. The peptide derivative disclosed by the invention is obtained by carrying out an amide reaction on KF7 peptide and levodopa, and the amino acid sequence of the KF7 peptide is shown as SEQ ID NO: 1. The polypeptide derivative has good biocompatibility, the surface modification method is simple, the modification process has no influence on cell life activity, activation, aggregation, expansion and adhesion of platelets can be inhibited, the bleeding risk is reduced, a blood coagulation system is not influenced, pancreas islet intrahepatic colonization and pancreas islet functions after portal transplantation are enhanced, and the application prospect is wide. The composition can protect pancreas islet, prevent infiltration of platelets and CD11b + cells, inhibit pancreas islet transplantation IBMIR reaction, control blood sugar level, and prevent and treat diabetes mellitus.

The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.

The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.

The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.

A Levodopa-selective sensor is provided. A continuous levodopa monitor is also provided. The levodopa sensor includes a sensor area having a working electrode with a levodopa-selective chemistry configured for at least partial implantation in a host. The sensor also includes at least one membrane adjacent the levodopa-selective chemistry. The at least one membrane includes an enzyme domain that at least one enzyme selected from a tyrosinase; a mutated tyrosinase with specificity towards I-3,4-dihydroxyphenylalanine; a dihydroxyphenylalanine 4,5-dioxygenase; a mutated dihydroxyphenylalanine 4,5-dioxygenase with specificity towards I-3,4-dihydroxyphenylalanine; and combinations thereof; a synthase enzyme with specificity towards I-3,4-dihydroxyphenylalanine; a mutated synthase enzyme with specificity towards I-3,4-dihydroxyphenylalanine; a 3,4-dihydroxyphenyl-acetaldehyde synthase; a mutated 3,4- dihydroxyphenyl-acetaldehyde synthase with specificity towards I-3,4-dihydroxyphenylalanine; a dioxygenase enzyme with specificity towards I-3,4-dihydroxyphenylalanine; and a mutated dioxygenase enzyme with specificity towards I-3,4-dihydroxyphenylalanine.

The application relates to the detection field and provides a method for detecting levodopa, which comprises the following steps: contacting a to-be-detected sample with a sensor to generate a detectable signal; the sensor comprises a working electrode, and the surface of the working electrode is loaded with UiO-66 material; a detection result of the to-be-detected sample is obtained based on the detectable signal; the Ui-O66 material is prepared by reacting terephthalic acid or a derivative thereof and a soluble zirconium salt for a predetermined time, and the predetermined time is determined based on known components of the to-be-detected sample. The method selects the reaction time of the UiO-66 material to regulate the proportion of the crystalline state and the amorphous state in the material, so that the detection requirement of the UiO-66 material for levodopa is accurately matched, the detection range covering from ultratrace (10 nM) to high concentration (300 nM), the method has high sensitivity, meanwhile, excellent selectivity and stability are considered, the detection requirement of different scenes is met, and the method is suitable for wide application.

The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.

The invention provides a method for analyzing polypeptide or protein in a to-be-detected sample, which comprises the following steps of: separating by reversed-phase high-performance liquid chromatography, measuring the content of free amino acid before and after hydrolysis of the to-be-detected sample by a detector, determining the amino acid composition of the polypeptide or protein according to the difference value, and indirectly reflecting the content of polypeptide or protein impurities. The analysis method disclosed by the invention has the characteristics of simplicity in operation, strong specificity, high accuracy, good reproducibility and the like, and is successfully applied to analysis research and quality control of residual polypeptide impurities in raw material medicines of levodopa and lacosamide.

The present application relates to a kind of synthetic hydroxytyrosol multi-enzyme catalytic method.The synthetic hydroxytyrosol multi-enzyme catalytic method described in the present application includes first module reaction, second module reaction, third module reaction in turn;The first module reaction is that glycerol is synthesized pyruvic acid by catalysis, wherein the concentration of the glycerol is 1-5mM;The second module reaction is that pyruvic acid is condensed with catechol and ammonium chloride to be L-levodopa by catalysis;Wherein, the concentration of the catechol is 1-5mM, and the concentration of the catechol is greater than the concentration of the glycerol in the first module reaction;The third module reaction is that L-levodopa is synthesized hydroxytyrosol by catalysis.The synthetic hydroxytyrosol multi-enzyme catalytic method described in the present application, reaction 4 hours hydroxytyrosol molar conversion rate can reach 71.5%, compared with one-pot method has obvious advantage, in the same reaction time molar conversion rate is compared with one-pot method and increased nearly 6 times.

This invention discloses a mutant of Mycobacterium tuberculosis tyrosine lyase and its applications, belonging to the fields of molecular biology and biocatalysis. This mutant, denoted as mutant I384V, is obtained by mutating isoleucine at position 384 of the Mycobacterium tuberculosis tyrosine lyase to valine. I384V has similar optimal temperature and pH to the wild-type tyrosine lyase, but exhibits higher specific enzyme activity and catalytic efficiency. Compared to the wild-type, the mutant I384V improves the synthesis efficiency of levodopa by 38.4%, showing broad prospects for large-scale industrial application.

Provided herein are methods of treating a neurodegenerative disorder (e.g., Parkinson's disease) or symptoms thereof in a patient by administering to the patient doxycycline (or a pharmaceutically acceptable salt thereof), either alone or in combination with other therapeutic agents (e.g., levodopa).

The application provides a biomarker dopamine-3-O-sulfate (DA3S) for evaluating the risk of movement complications of Parkinson's disease patients. The application also provides a cerebrospinal fluid kit for evaluating the risk of movement complications of Parkinson's disease patients. The application is based on the concentration of DA3S in cerebrospinal fluid, and combines with clinical variables such as daily dose of levodopa (LEDD), disease duration, etc. to construct a joint prediction model, so as to realize early and quantitative individualized evaluation of the risk of movement complications of Parkinson's disease patients. The application also provides a plasma kit and a urine kit for evaluating the risk of movement complications of Parkinson's disease patients.

The invention relates to application research of Dunaliella sp. Or metabolites thereof in preparation of drugs for prevention or treatment of Parkinson's disease, Dunaliella sp. Can produce L-DOPA and analogues thereof through metabolism, and the Dunaliella sp. Is a promising drug for treatment of Parkinson's disease. In addition, the main metabolite indoleacetic acid (IAA) of the dunaliella can significantly improve the dyskinesia of PD mice, relieve the loss of dopaminergic neurons in the brain and reduce neuroinflammation, thereby delaying the PD process. The intestinal symbiotic bacterium Dunaliella sp. And the metabolite thereof provided by the invention have a good effect of treating or preventing Parkinson's disease, and the Dunaliella sp. Metabolites to generate L-DOPA and analogues thereof, so that the Dunaliella sp. Is a potential PD treatment medicine and is suitable for clinical popularization.

The invention provides adhesive type gastric retention administration hydrogel as well as a preparation method and application thereof, and belongs to the technical field of bioactive materials and drug delivery methods. The drug delivery hydrogel is prepared by taking levodopa modified hyaluronic acid as a skeleton structure, gluconic acid-delta-lactone as an acidity regulator and potassium sorbate as a preservative. The preparation method comprises the following steps: grafting levodopa onto hyaluronic acid, dialyzing, and freeze-drying to obtain levodopa modified hyaluronic acid; gluconic acid-delta-lactone, potassium sorbate and levodopa modified hyaluronic acid are mixed and dissolved in water, and after a reaction, the drug delivery hydrogel is obtained. Anthocyanin is loaded in administration hydrogel to prepare the gastric retention sustained-release medicinal preparation. The prepared drug delivery hydrogel has good oxidation resistance, biocompatibility, adhesion and drug sustained-release capacity, the hydrogel is endowed with sustained-release drug delivery capacity through the wet adhesion effect in the stomach wall environment, and the drug delivery hydrogel is widely applied to the fields of bioactive materials, drug delivery and food.

This invention discloses a tyrosine phenol lyase mutant and its application in synthesizing tyrosine derivatives. The mutant is obtained by single or multiple mutations at position 18 or 417 of the amino acid sequence shown in SEQ ID NO.2. Compared with the wild type, the tyrosine phenol lyase mutant provided by this invention exhibits superior enzyme activity and catalytic performance. The TPL mutant synthesizes levodopa at a cumulative concentration of over 160 g / L, L-tyrosine at a cumulative concentration of over 80 g / L, 3,4,5-TOPA at a cumulative concentration of over 16.4 g / L, 3-fluoro-L-tyrosine at a cumulative concentration of over 33.1 g / L, and 2-fluoro-L-tyrosine at a cumulative concentration of over 20.5 g / L, with an optical purity greater than 99.9%.

The invention belongs to the technical field of probiotics, and particularly relates to lactobacillus reuteri HuYan with an eye protection effect and application of the lactobacillus reuteri HuYan. According to the invention, a novel lactobacillus reuteri HuYan strain is separated from feces of a healthy infant in Guangzhou city, Guangdong province, and the lactobacillus reuteri HuYan strain can significantly reduce vascular hyperplasia and cell apoptosis of eyes, inhibit eye shrinkage, reduce the number of neutrophils in the eyes, reduce the content of levodopa and increase the content of levo5-hydroxytryptamine. Therefore, the strain can be applied to prevention and treatment of eye vascular dysplasia related diseases, protection of intraocular cells to avoid apoptosis, improvement or prevention of eye shrinkage and alleviation of eye inflammation, has positive significance in protection of eye tissues and maintenance of normal physiological status of eyes, is expected to be used in the fields related to prevention and treatment of eye diseases, and has wide application prospects. Wide application prospects are realized in the field of treating and preventing eye diseases.

The application provides application of N-acyl dopamine family lipids in prevention and treatment of drug-induced Parkinson's disease motor complications, and belongs to the field of biological medicine. The application first proposes that the NADs compound can be used as a levodopa companion drug for preventing or treating levodopa-induced dyskinesia. The application takes 6-hydroxydopamine intracerebral injection and intraperitoneal injection of levodopa of an LID animal model as a research object, and studies the effect of NADs on improving LID. The results show that the NADs of the application can significantly improve the drug-induced PD motor complications LID, and it is proved that the NADs compound can be used as a companion drug to assist levodopa in treating PD.

Pharmaceutical composition for use in the prophylactic and / or therapeutic treatment of dyskinesias induced by L-DOPA. The present invention relates to the pharmaceutical field, more particularly to the use of Rho kinase inhibitors for treating or preventing dyskinesias induced by L-DOPA.

This invention relates to the field of biomedical materials technology, and more particularly to a flexible patch for treating nervous system diseases and its preparation method. It comprises: a flexible, breathable substrate composed of silk fibroin nanofibers, and drug-loaded nanoparticles loaded within the substrate; the drug-loaded nanoparticles are encapsulated with chitosan and contain levodopa and copper oxide nanoenzymes; the silk fibroin nanofibers are annealed with ethanol to form a controllable degradation structure, achieving self-adhesion and continuous drug release in a humid environment. This patch can simultaneously achieve stable delivery of dopamine and scavenging of reactive oxygen species, thus addressing the motor complications and neurooxidative damage caused by fluctuations in blood drug concentration in traditional Parkinson's disease treatment, achieving a dual synergistic treatment of symptom relief and neuroprotection.

The application discloses a levodopa plasma exposure reconstruction and pharmacokinetics inference method, system, device and storage medium based on multi-body fluid observation fusion and capillary blood anchor updating, the application breaks through the limitation of single body fluid observation through multi-body fluid observation fusion, can more comprehensively and accurately obtain the relevant information of levodopa in the body, provides more abundant and accurate data support for plasma exposure reconstruction, secondly, the capillary blood anchor updating mechanism can calibrate and update the related data in real time and dynamically, ensure the accuracy and timeliness of plasma exposure reconstruction, the combination of multi-body fluid observation fusion and capillary blood anchor updating mechanism innovation effectively improves the accuracy of levodopa plasma exposure reconstruction and the reliability of pharmacokinetics inference, can better assist medical personnel to understand the metabolism of levodopa in the patient's body, has important clinical application value and broad market prospect.

The present invention relates to a recombinant microbial host cell comprising an operative biosynthetic metabolic pathway capable of producing one or more compounds selected from the group consisting of L-dopa, dopamine, (S)-Norcoclaurine and derivatives thereof; said pathway comprising a heterologous L-tyrosine hydroxylase (TyrH) converting L-Tyrosine into L-dopa capable of increasing the cell production of the Compound compared to a reference L-tyrosine hydroxylase having the sequence set forth in SEQ ID NO: 58.

The invention discloses an application of a metabolite in diagnosis of diabetes mellitus. The metabolite is levodopa. According to the invention, the metabolite as the biomarker shows significant difference between diabetic patients and healthy people for the first time, and has a relatively high AUC value, which prompts that the metabolite marker has a relatively high diagnostic value in diabetes mellitus.

The invention discloses a copper-doped polymeric amino acid modified sensing electrode, a preparation method and an instant electrochemical detection method of levodopa, belongs to the technical field of analysis sensing detection, and relates to a detection method of levodopa. According to the invention, polydopamine, graphene oxide and a copper-doped amino acid modified electrode are adopted to obtain the copper-doped polymeric amino acid modified sensing electrode. According to the method, the binding principle of tyrosinase and levodopa is utilized, specific recognition of levodopa is achieved by simulating a tyrosine recognition mechanism, low-concentration levodopa can still be detected even under the condition that common drugs and other interferents exist in a detection sample, detection can be achieved after multiple times of repetition, and the detection efficiency is greatly improved. And the stability is good. Meanwhile, due to the excellent anti-interference performance and reusability, the detection cost is greatly reduced, and application and popularization in actual clinical work are facilitated.

The invention provides a gene, a biological material and a method for regulating and controlling histidine content in crops, and belongs to the technical field of gene engineering. The invention provides a TaATL15 gene for regulating and controlling the histidine content in crops, and the amino acid sequence of protein coded by the TaATL15 gene is shown as SEQ ID No.3. The TaATL15 gene is transformed into wheat through a genetic transformation method by utilizing the TaATL15 gene, so that a TaATL15 overexpression transgenic plant is obtained, and the histidine content in the crops is regulated and controlled. And the contents of histidine, tyrosine and levodopa in the TaATL15 overexpression transgenic plant are obviously increased.