16 results about "Clozapine" patented technology

The invention relates to the technical field of medicines, and discloses six adeno-associated virus (AAV) injections carrying novel artificial chemical genetics receptor gene sequences, and a combinatorial chemical genetics scheme formed by the injections and a small molecule agonist quetiapine. Compared with the traditional chemical genetics, the medicine quetiapine with smaller clinical side effect is used as the activating agent for the first time, and a novel chemical genetics system with lower medication risk is developed. The system can effectively reduce the excitatory activity of neurons, avoids the medication risk caused by clozapine or other non-market traditional chemical genetics activators, and improves the feasibility of clinical transformation of the chemical genetics system. In the aspect of application of a novel or traditional chemical genetics system, the combined treatment scheme is applied to intervene in Parkinson's disease (PD) for the first time, abnormal activities of STN and related loops of PD patients can be inhibited, and the dyskinesia symptom can be remarkably improved.

The invention relates to the technical field of medicines, and discloses an adeno-associated virus (AAV) injection carrying an artificial chemical genetics receptor gene sequence, and a combinatorial chemical genetics scheme formed by the adeno-associated virus injection and a small molecule agonist quetiapine. Compared with the traditional chemical genetics, the medicine quetiapine with smaller clinical side effect is used as the activating agent for the first time, and a novel chemical genetics system with lower medication risk is developed. The system can effectively reduce the excitatory activity of neurons, avoids the medication risk caused by clozapine or other non-market traditional chemical genetics activators, and improves the feasibility of clinical transformation of the chemical genetics system. In the aspect of application of a novel or traditional chemical genetics system, the combined treatment scheme is applied to intervene in Parkinson's disease (PD) for the first time, abnormal activities of STN and related loops of PD patients can be inhibited, and the dyskinesia symptom can be remarkably improved.

A method for treating a mental disorder in a subject, comprising the step of normalizing the expression of both DRD1 and DRD5 belonging to the DRD1-like family of the subject to a preset standard level. The DRD1 / 5 level and expression can be increased or decreased bidirectionally by targeting the upstream promoter sequence of DRD1 / 5. The promoter activity of DRD1 / 5 can be attenuated by using antipsychotic drugs that directly target the DRD1 / 5 promoter. The antipsychotic drugs used are typical and / or atypical antipsychotic drugs such as haloperidol, risperidone, clozapine, and cariprazine. This treatment is also useful for subjects in whom the constitutive expression of the DRD1 / 5 gene is impaired. This method can be used to treat schizophrenia, autism, depression, mania, and bipolar disorder by normalizing the DRD1 / 5 expression level. The promoter gene sequencing of DRD1 and / or DRD5 can also be used for quantitative mental health screening by comparing with a standard sequence database.

The group of inventions relates to medicine, pharmacology, namely to psychiatry and can be used for effective and safe treatment of mental disorders associated with dysfunction of dopamine and serotonin (5-hydroxytryptamine) neurotransmitter systems. Pharmaceutical compositions containing halogenated clozapine, in an amount effective as selective antagonists of D4 and 5NT2A receptors, and at least one pharmaceutically acceptable carrier, as well as their use and methods of treatment are offered for this purpose. The inventions make it possible to create a new drug with a well-balanced receptor profile, the intake of which will allow to treat mental disorders in an effective way without causing side effects associated with exposure to receptors that are not involved in the pathology of a mental disorder.

The invention discloses a detection method for determining N-methylpiperazine in clozapine, and belongs to the technical field of drug detection, the detection method comprises solution preparation and detection; in the step of preparing the solution, clozapine is used for preparing a test solution, and N-methyl piperazine is used for preparing a reference solution; the detection comprises the following steps: determining the test solution and the reference solution by adopting a liquid chromatography-mass spectrometry method, recording a chromatogram, and calculating the content of N-methyl piperazine; in the detection, the conditions of liquid chromatography are as follows: a mobile phase is composed of a mobile phase A and a mobile phase B, and the mobile phase A is an aqueous solution of 0.048-0.052% trifluoroacetic acid; the mobile phase B is acetonitrile; according to the method, the genotoxic impurity N-methylpiperazine in the clozapine raw material medicine and the preparation can be quantitatively detected, the content of the impurity in the clozapine production and storage process can be conveniently monitored, the selectivity is high, the sensitivity is good, and the limit of quantitation can be as low as 0.165 ppm.

An object of the present invention to provide a clozapine-induced sialorrhea alleviator. The clozapine-induced sialorrhea alleviator of the present invention contains as an active ingredient dextromethorphan, a compound having an antagonistic action on an NMDA-type glutamate receptor, or a compound having an agonistic action on a sigma-1 receptor.

The application relates to the technical field of medicines, and discloses six adeno-associated virus (AAV) injection solutions carrying novel artificial chemical genetic receptor gene sequences and a combined chemical genetic scheme formed by the AAV injection solutions and a small-molecule agonist quinpirole. Compared with traditional chemical genetics, the application first uses the drug quinpirole with smaller clinical side effects as an activator to develop a novel chemical genetic system with lower drug risk. The system can effectively reduce the excitatory activity of neurons, avoid the drug risk brought by clozapine or other non-marketed traditional chemical genetic activators, and improve the feasibility of clinical transformation of the chemical genetic system. In the application of the novel or traditional chemical genetic system, the application first applies the combined treatment scheme to intervene in Parkinson's disease (PD), can inhibit the abnormal activity of STN and related circuits of PD patients, and significantly improves the symptoms of dyskinesia.

The invention relates to the technical field of medicines, and discloses six adeno-associated virus (AAV) injections carrying novel artificial chemical genetics receptor gene sequences, and a combinatorial chemical genetics scheme formed by the injections and a small molecule agonist quetiapine. Compared with the traditional chemical genetics, the medicine quetiapine with smaller clinical side effect is used as the activating agent for the first time, and a novel chemical genetics system with lower medication risk is developed. The system can effectively reduce the excitatory activity of neurons, avoids the medication risk caused by clozapine or other non-market traditional chemical genetics activators, and improves the feasibility of clinical transformation of the chemical genetics system. In the aspect of application of a novel or traditional chemical genetics system, the combined treatment scheme is applied to intervene in Parkinson's disease (PD) for the first time, abnormal activities of STN and related loops of PD patients can be inhibited, and the dyskinesia symptom can be remarkably improved.

The invention belongs to the crossing field of bioinformatics and precision medical treatment, and particularly relates to a method for screening clozapine markers for treating schizophrenia based on a sequencing technology. The method comprises the following steps: firstly, constructing a schizophrenia animal model, performing drug intervention by using clozapine, obtaining a prefrontal lobe cortex tissue transcriptome map of the animal model before and after drug administration through a high-throughput sequencing technology, and learning a screening strategy by using two machines, secondly, a gene expression model associated with side effects is established by using LASSO regression analysis, five specific side effect marker genes Aff2, Apoo, Auh, Mrp153 and Trim66 are determined, a curative effect evaluation index model is finally constructed, and double indexes of treatment effect prediction and side effect risk are output from a single sample; technical support can be provided for diagnosis and treatment of schizophrenia.

The present invention relates to a clozapine cocrystal having advantages in humidity stability and solubility and a preparation method thereof, and relates to the technical field of drug cocrystals. Specifically, the clozapine cocrystal is formed by combining clozapine with a cocrystal former. The cocrystal former includes any one of maleic acid, oxalic acid, fumaric acid, succinic acid and citric acid. The preferred clozapine cocrystal of the present invention has good humidity stability, which is conducive to the long-term storage of the drug. In addition, compared with the original drug clozapine which is almost insoluble in water, the preferred clozapine cocrystal disclosed in the present invention significantly improves the solubility of clozapine. The clozapine cocrystal having advantages in humidity stability and solubility can better achieve the effectiveness of the production and clinical application of clozapine.

A method of treatment of mental disorder of a subject includes the steps of: normalizing an expression of both DRD1 and DRD5, which belong to DRD1-like family, of the subject to a preset standard level. The DRD1 / 5 level and expression can be increased or decreased bidirectionally by targeting an upstream promoter sequence of DRD1 / 5. The promoter activity of DRD1 / 5 can be attenuated by using an antipsychotic which directly targets the DRD1 / 5 promoter. The antipsychotics being used are typical and / or atypical antipsychotic medications such as Haloperidol,Risperidone, Clozapine and Cariprazine. The treatment is also useful for the subject with an impaired constitutive expression of DRD1 / 5 gene. The method can be used to treat schizophrenia, autism, depression, mania and bipolar disorders by normalizing the DRD1 / 5 expression level. The promoter gene sequencing of DRD1 and / or DRD5 can also be used for quantitative mental health screening through comparing with a standard sequence database.

The present application relates to neuropsychopharmacology technical field, disclose a kind of pharmaceutical composition, comprising 5-HT1D receptor antagonist and clozapine, 5-HT1D receptor antagonist is CNI3176 or its pharmaceutically acceptable salt, clozapine and the 5-HT1D receptor antagonist is arranged sequentially sequential administration, and the clozapine is administered before the 5-HT1D receptor antagonist, after clozapine administration, 5-HT1D receptor antagonist is administered again with 15-60 minutes interval.Therein, the present application first discloses that 5-HT1D receptor antagonist and low-dose clozapine exist significant synergistic effect on antipsychotic effect.Animal experiment shows that, under the subthreshold dose that clozapine is invalid alone, combined with intranasal administration CNI3176 can produce the effect of completely reversing psychotropic behavior, curative effect is equivalent to even superior to high-dose clozapine single-drug treatment.

The purpose of the present invention is to provide an ameliorating agent for clozapine-induced salivation. The clozapine-induced salivation ameliorating agent according to the present invention contains dextromethorphan, a compound having an antagonistic effect on NMDA-type glutamate receptors, or a compound having an agonistic effect on sigma-1 receptors as an active ingredient.

The present invention provides an extended release pharmaceutical composition of Clozapine, wherein the said pharmaceutical composition is a reservoir type dosage form, and when dosed to a patient once daily achieves at steady state, AUC0-24h, Cmax and Cmin in the patient's plasma that are within 80 to 125 % bioequivalence criteria compared to immediate release Clozapine dosed at the same total daily dose divided twice per day. Further, the said pharmaceutical composition of Clozapine according to the present invention provides once daily dosing regimen in order to improve patient compliance and reduces side effects in patients in need thereof. Furthermore, the said pharmaceutical composition of Clozapine lacks a significant food effect on oral administration.

This invention discloses the application of clozapine and its combination with chemotherapeutic drugs in the preparation of drugs for treating triple-negative breast cancer or breast cancer stem cells, belonging to the field of pharmaceutical technology. This invention experimentally verifies that clozapine can effectively inhibit the growth of breast cancer stem cells and has a strong growth-inhibiting effect on triple-negative breast cancer cell lines, but has no growth-inhibiting effect on other types of breast cancer cell lines and normal tissue cells, thus it can be used as a treatment drug for triple-negative breast cancer. Simultaneously, the combination of clozapine and chemotherapeutic drugs can significantly inhibit the growth of triple-negative breast cancer cells, and the inhibitory effect is significantly better than that of chemotherapeutic drugs alone. Clozapine alone and the combination of clozapine and chemotherapeutic drugs significantly inhibited the growth of triple-negative breast cancer tumors in mouse models, successfully solving the problem of drug resistance in triple-negative breast cancer caused by the inability of existing basic treatment drugs (chemotherapeutic drugs) to inhibit breast cancer stem cells.

The application discloses a detection method for N-methyl piperazine in clozapine, and belongs to the technical field of drug detection. The detection method comprises solution preparation and detection. The solution preparation uses clozapine to prepare a test sample solution and uses N-methyl piperazine to prepare a control sample solution. The detection adopts liquid chromatography-mass spectrometry to determine the test sample solution and the control sample solution, records a chromatogram, and calculates the content of N-methyl piperazine. In the detection, the conditions of the liquid chromatography are as follows: a mobile phase is composed of mobile phase A and mobile phase B, the mobile phase A is a 0.048-0.052% trifluoroacetic acid aqueous solution, and the mobile phase B is acetonitrile. The application can quantitatively detect the genotoxic impurity N-methyl piperazine in clozapine bulk drug and preparations, is convenient for monitoring the content of the impurity in the production and storage process of clozapine, and is high in selectivity, good in sensitivity, and low in quantitative limit to 0.165 ppm.