135 results about "Levodopa" patented technology

The invention discloses a tyrosine phenol lyase mutant and application of the tyrosine phenol lyase mutant in synthesis of a tyrosine derivative. The mutant is obtained by performing single mutation or multiple mutation on the 18th site or the 417th site of an amino acid sequence shown in SEQ ID NO.2. Compared with a wild type, the tyrosine phenol lyase mutant provided by the invention has more excellent enzyme activity and more excellent catalytic performance. According to the TPL mutant, the cumulative concentration for synthesizing levodopa is up to 160 g / L or above, the cumulative concentration for synthesizing L-tyrosine is up to 80 g / L or above, the cumulative concentration for synthesizing 3, 4, 5-TOPA is up to 16.4 g / L or above, the cumulative concentration for synthesizing 3-fluoro-L-tyrosine is up to 33.1 g / L or above, the cumulative concentration for synthesizing 2-fluoro-L-tyrosine is up to 20.5 g / L or above, and the optical purity is greater than 99.9%.

The invention discloses a tyrosine phenol lyase mutant and application of the tyrosine phenol lyase mutant in synthesis of levodobar. The tyrosine phenol lyase mutant is obtained by carrying out site-specific mutagenesis on the basis of wild type tyrosine phenol lyase. The mutant obtained through transformation can transform more substrates, the yield is also obviously improved, and the method is suitable for industrial production of levodopa.

The invention provides oral dosing regimens of controlled release levodopa compositions for use in treating patients with Parkinson's disease.

The invention is a method for treating patients with Parkinson's disease, primary parkinsonism / idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication and provides an improvement of a patient's total post-dose “On” time or “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 provides an oral solid formulation comprising (a) a controlled release component comprising a core comprising levodopa, wherein the core is coated with a muco-adhesive coating and the muco-adhesive coating is externally coated with an enteric coating; and (b) an immediate release component comprising levodopa. The invention further provides a method for making and using the oral solid formulation.

The invention is a method for treating patients with Parkinson's disease, primary parkinsonism / idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication and provides an improvement of a patient's total post-dose “On” time or “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.

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 invention discloses a mycobacterium tuberculosis tyrosine phenol lyase mutant and application thereof, and belongs to the field of molecular biology and the technical field of biological catalysis. The mutant is obtained by mutating 384 isoleucine of tyrosine phenol lyase from mycobacterium tuberculosis into valine, and is marked as a mutant I384V. The I384V and wild type tyrosine phenol lyase have similar optimum temperature and optimum pH, but the I384V shows higher specific enzyme activity and catalytic efficiency than the wild type tyrosine phenol lyase. Compared with a wild type, the tyrosine phenol lyase mutant I384V has the advantages that the synthesis efficiency of the tyrosine phenol lyase mutant I384V on the synthesis of levodopa is improved by 38.4%, and the tyrosine phenol lyase mutant I384V has wide prospects in large-scale industrial application.

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 is a method for treating patients with post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” 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 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 discloses a heterozygote of 3-hydroxylase and application of the heterozygote in production of levodopa, caffeic acid or hydroxytyrosol, and relates to the technical field of biology. The heterozygote of the 3-hydroxylase comprises HpaB and HpaC, and the 3-hydroxylase comprises HpaB and HpaC. The limitation of the catalytic efficiency of hydroxylase in the prior art is overcome, the production efficiency of levodopa, caffeic acid or hydroxytyrosol is remarkably improved, and the method has a very good application prospect. The expression levels of HpaB and HpaC are properly regulated and controlled by using connecting element sequences such as a connecting peptide sequence and a 5 '-UTR sequence, so that a better production effect can be obtained.

The invention provides an oral solid formulation comprising (a) a controlled release component comprising a core comprising levodopa, wherein the core is coated with a muco-adhesive coating and the muco-adhesive coating is externally coated with an enteric coating; and (b) an immediate release component comprising levodopa. The invention further provides a method for making and using the oral solid formulation.

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.

The invention provides an application of N-acyl dopamine family lipids in prevention and treatment of drug-induced motor complications of Parkinson's disease, and belongs to the field of biological medicine. The invention provides the application of the NADs compound as the levodopa partner medicine for preventing or treating levodopa-induced dyskinesia for the first time. According to the invention, an LID animal model is subjected to 6-hydroxydopamine midbrain nigra positioning injection and levodopa intraperitoneal injection molding as research objects, and the effect of NADs in improving LID is researched. The result shows that the NADs can significantly improve the drug-induced PD motor complication LID, indicating that the NADs compound can be used as a partner drug to assist levodopa in treating PD.

A levodopa derivative, including a compound or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, where the compound includes substituents comprising in total at least 6 carbon atoms that bind only to other carbon atoms or hydrogen atoms. The levodopa derivatives may be formulated as compositions that include one or more pharmaceutically acceptable carriers or excipients. The levodopa derivative may be part of a pharmaceutical composition, including microparticles or nanoparticles, in which the levodopa derivative is encapsulated in a pharmaceutically acceptable polymer. Levodopa derivatives may be used to treat Parkinson's disease by administering to a mammal an amount sufficient to treat Parkinson's disease.

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 invention discloses a multi-effect compound scar-removing gel for repairing sensitive muscle scars and a preparation method of the multi-effect compound scar-removing gel, and belongs to the technical field of preparation of medical preparations for skin. The multi-effect compound scar-removing gel is prepared from the following raw materials in percentage by weight: 0.05 percent to 0.08 percent of recombinant III type humanized collagen, 0.63 percent to 0.66 percent of carbomer, 0.18 percent to 0.21 percent of sodium phosphosilicate calcium, 0.09 percent to 0.11 percent of gamma-polyglutamic acid, 1.6 percent to 2.2 percent of levodopa-amino silicon oil mixed liquid, 0.8 percent to 1.1 percent of oxidized ganoderma lucidum polysaccharide and the balance of deionized water. The preparation method comprises the following steps: mixing and dispersing recombinant III-type humanized collagen, carbomer, calcium sodium phosphosilicate, polyglutamic acid, a levodopa-amino silicon oil mixed solution, oxidized ganoderan and deionized water to form a dispersion solution; then, the dispersion liquid is adjusted to be in a weakly alkaline environment for cross-linking and then is adjusted to be neutral for standing and gelation, and the obtained multi-effect compound scar-removing gel is effective and good in scar repair and does not have a red and swollen irritation phenomenon.

The present invention provides a levodopa derivative, including a compound or a pharma- ceutically acceptable salt, hydrate, and / or solvate thereof, the compound including, in its entirety, a substituent that contains at least six carbon atoms that are bonded only to either other carbon atoms or to hydrogen atoms. The levodopa derivative may be formulated as a composition including one or more pharma- ceutically acceptable carriers or excipients. The levodopa derivative may be part of a pharmaceutical composition including microparticles or nanoparticles in which the levodopa derivative is encapsulated in a pharma- ceutically acceptable polymer. The levodopa derivative may be used to treat Parkinson's disease by administering to a mammal an amount sufficient to treat Parkinson's disease.

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.