28 results about "TRPM8" patented technology

The invention provides a TRPM8 protein mutant and application thereof, relative to an amino acid sequence of a wild type TRPM8 protein, the TRPM8 protein mutant comprises mutation at one or more positions selected from the 825th site, the 864th site, the 891th site, the 897th site, the 915th site, the 917th site, the 925th site, the 927th site, the 928th site, the 932th site, the 945th site, the 946th site and the 948th site. The invention also provides a separated nucleic acid which is used for coding the TRPM8 protein mutant. The invention also provides a vector containing the isolated nucleic acid and a genetically recombinant porcine fetal fibroblast. According to the invention, a key site which can effectively reduce the cold activation level of the pig TRPM8 without influencing other activation functions is screened, and a new material is provided for animal breeding improvement.

Described herein are modified monoterpene TRPM8 activating compounds. In particular, provided herein are compounds that affect intracellular ion channel function, and are useful as or in conjunction with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and disorders, including inflammatory eye diseases (e.g., uveitis), cardiovascular diseases, inflammatory diseases, and diseases characterized by aberrant hyperplasia (e.g., cancer).

The invention provides application of a TRPM8 inhibitor in improving the production performance of animals under cold conditions and a method. Specifically, the invention provides application of a TRPM8 inhibitor in preparation of a product for reducing adaptive heat production of animals under cold conditions and a method for reducing adaptive heat production of animals under cold conditions, and the method comprises the following steps: adding the TRPM8 inhibitor into animal feed to obtain mixed feed; and feeding the animal with the mixed feed. The TRPM8 inhibitor is used as an animal feed additive, so that adaptive heat production of animals is reduced, and production traits and economic values of the animals are improved.

The present invention pertains to a multiple biomarker for cancer diagnosis and a use thereof and, specifically, to a composition for cancer diagnosis, comprising an agent for measuring the protein or mRNA expression levels of IGFI, KLK2, PKCα, and TRPM8. The present inventors confirmed that rapid and accurate cancer diagnosis can be performed by detecting the unique marker combination of IGFI, KLK2, PKCα, and TRPM8 of the present invention in serum samples from actual cancer patients and one or more cancers can be simultaneously detected. Thus, the combination of IGFI, KLK2, PKCα, and TRPM8 is expected to allow for the rapid and accurate diagnosis of various cancers including prostate cancer.

The application relates to the field of biological medicines, and discloses a method for screening a TRPM8 antagonist, which comprises the following steps: step 1, contacting a candidate substance with a TRPM8 protein or a functional fragment thereof, wherein the TRPM8 protein or the functional fragment thereof at least contains 796D, 861Q and 862R amino acid residues; step 2, detecting whether the candidate substance is specifically combined with at least one residue in the TRPM8 protein or the functional fragment thereof; and step 3, if combined and at the same time can produce an allosteric effect on the protein, it can be preliminarily judged that the candidate substance is a TRPM8 antagonist. The application fills the gap of the existing technology about the TRPM8 binding mode and the screening method by disclosing the key residues and the allosteric binding pocket of the TRPM8 protein combined with the antagonist, and promotes the clinical application transformation of the TRPM8 antagonist in the fields of neuropathic pain, antitumor and bone repair.

The invention provides a Yao medicine characteristic powerful external plaster for treating gout acute joint pain, and relates to the field of plasters, a preparation method comprises the following steps: S100, crushing a matrix until the particle size is less than or equal to 2 mm, adding 200 g of oil into per kilogram of the matrix, the oil being selected from soybean oil, rapeseed oil, sesame oil or blend oil; s200, heating with a soft fire of 50-80 DEG C until the matrix is completely dissolved to form a homogeneous oil phase; and S300, slowly adding 1000g of medicinal powder into the oil phase, and decocting at a stirring speed of 20-30r / min for 40-60 minutes until the color of the mixture becomes dark brown or black. According to the plaster, the borneol and the mentholum have a synergistic effect, so that the plaster can quickly permeate skin, a local ice feeling can be generated within 5 minutes after the plaster is applied, the median onset time is 20-30 minutes, and the plaster is obviously superior to an oral medicine, the tripterygium wilfordii extract inhibits the activity of xanthine oxidase, the scandent schefflera stem and leaf blocks an IL-1beta inflammation pathway, and the borneol is assisted to stimulate a TRPM8 receptor, so that the curative effect of the plaster is improved. And the pain relief rate is increased to 50-70%.

The invention relates to application of anacycline A in preparation of analgesic drugs, in particular to an anacycline A compound separated from anacycline roots. The compound can be applied to analgesic drugs with inhibition effects on transient receptor potential cation channel subfamily M member 8 (TRPM8), a voltage-gated potassium ion channel 1.2 (Kv1.2), a voltage-gated potassium ion channel 1.3 (Kv1.3), transient receptor potential cation channel protein 6 (TRPC6) and a voltage-gated calcium ion channel 2.1 (Cav2.1), in particular to drugs for neuropathic pain, traumatic pain or inflammatory pain. The compound anacycline A can be combined with a plurality of analgesia-related targets, so that a synergistic effect is generated, the treatment effect is enhanced, and meanwhile, side effects and drug resistance are reduced.

The present invention provides a method for effectively reducing corneal fluorescein staining (CFS) or improving corneal health, which includes administering a therapeutically effective amount of a TRPM8 agonist to a subject in need thereof, wherein the TRPM8 agonist comprises a DIPA compound (e.g., DIPA-9). The novel therapeutic use of the TRPM8 formulations according to the present invention may demonstrate improved efficacy through reduced CFS or SANDE.

The present invention provides a method for treating an ocular disorder in a subject in need thereof, comprising topically administering a therapeutically effective amount of a TRPM8 agonist to surfaces of ocular margin of the subject, wherein the ocular margin is the primary target site for delivery of the TRPM8 agonist. The method may use a wiping, brushing, or spraying approach, and is more effective and efficient than the conventional method using eye drops.

Patients suffering from rhinitis and rhinosinusitis often experience symptoms such as nasal discharge, congestion, sniffles, and excess phlegm secretion. These symptoms can cause a feeling of impaired airflow, loss of patency, and uncomfortable breathing. In this context, a treatment method is proposed to alleviate these signs and symptoms. The drug target is the TRPM8 receptor on nerve fibers of the ostiomeatal complex. The active ingredient, a TRPM8 agonist, is delivered using an electronically controlled nebulizer that produces a vigorous air plume of defined particle sizes, which prevents entry into the lungs. The quantity of phlegm expelled from the nasal passage is used as an index of anti-inflammatory effectiveness. The optimized drug candidates for delivery and therapy are from a group of p-menthanecarboxamides. Preferred embodiments of these include the p-menthane amino acid esters: GlyOnPr, GlyOiPr, D-Ala-OnPr, and D-Ala-OiPr, delivered as a liquid suspension or solution at 0.1 to 1% (1 to 10 mg / mL), 0.5 to 0.8 mL per nostril over 3 to 5 seconds, using a nebulizer. This regimen, administered three times per day for three to five days, will help the patient manage and control their nasal congestion and phlegm secretion, and sleep better at night. The preferred embodiments delivered into the nasal cavity create a sense of cool breathing, refreshing coolness, and a feeling of negative heat flux, like an air conditioner in the nose. The secretion of phlegm is clearly decreased, as measured with a top-loading balance. This pharmacological treatment for patients with nasal inflammation has the potential to alter the course of rhino-disorders permanently.

The application belongs to the technical field of genetic engineering, and particularly relates to a method for screening cool substances by using a TRPM8 stable cell strain and construction of a cell model thereof. TRPM8 The cell model comprises a vector, and the vector comprises TRPM8 a gene, and a nucleotide sequence of the gene is shown in SEQ ID No: 1. TRPM8 The application provides an application of the gene in cool substance evaluation. TRPM8 The application adopts the gene to construct a cell model, and then adopts a cool substance to treat the cell model, and finally detects a relative value of fluorescence intensity of the cell model to evaluate the cool substance.

The present invention provides an application of a mouse taste bud tissue biosensor in screening TRPM8 antagonists. The mouse taste bud tissue biosensor is constructed by using a screen-printed electrode as a detection device and a mouse taste bud tissue membrane as an identification element. The tissue biosensor method has high sensitivity, strong specificity, small sample volume, and a detection concentration as low as 10 ‑ 22 mol·L ‑1 The invention also achieved the screening of TRPM8 receptor antagonists from candidate natural compounds in traditional Chinese medicine by analogy with enzymatic reaction kinetics. This invention forms a set of methods for screening TRPM8 receptor antagonists based on mouse taste bud tissue sensors.

The invention provides a risk dynamic assessment method for a cross-climate zone diabetic foot, which comprises the following steps: when a user moves to a target climate zone, collecting environmental data of the target climate zone, functional indexes of a user foot TRPM8 channel and user individual data; calculating a basic stress index according to the environment data, and correcting the basic stress index through the function index and the user individual data to obtain a final stress index; drawing an index change curve of the user based on the final stress index, processing the index change curve, the function index and the user individual data through a double-branch neural network, and outputting double-branch features; fusing the double-branch features through an attention mechanism, and outputting the functional damage level of the TRPM8 channel; performing risk dynamic assessment according to the functional damage level, and outputting intervention measure suggestions; by establishing the dynamic association of the environmental-TRPM8-diabetic foot risk, accurate risk assessment and personalized intervention in a cross-climate-zone scene can be realized.

Provided are the use of specific polypeptides in the preparation of drugs for treating and preventing prostate cancer, and the use of specific polypeptides in the preparation of immunological inducers. The specific polypeptides are derived from TRPM8 protein and have good effects on the treatment and prevention of prostate cancer at various stages, especially androgen-independent prostate cancer.

The invention discloses an application of sotrasturin, or a stereoisomer of sotrasturin, or a raceme of sotrasturin, or a pharmaceutically acceptable salt of sotrasturin, or a solvate of sotrasturin in the development of a medicine for preventing or treating TRPM8 related diseases. Particularly, sotratolin is disclosed as a TRPM8 agonist, and a good prevention or treatment effect can be obtained when sotratolin is used for preventing or treating xerophthalmia; in a mouse xerophthalmia model induced by a benzalkonium chloride solution, sotratoline has a remarkable improvement effect.

The present invention provides an advanced coolant composition comprising a volatile agent and a moisturizing lubricant, where the volatile agent comprises ethanol and water, and a non-volatile solvent comprises a diol, glycerol, hyaluronic acid, menthol, and sterol compounds, and is free of any pharmaceutically active ingredient for treating erectile dysfunction. Hyaluronic acid and a sterol compound are self-assembled to form a nanoscale lamellar liquid crystal structure, so that the skin barrier function is kept complete while the transdermal efficiency is improved, and an instantaneous calcium signal activated by a menthol substance TRPM8 receptor and eNOS continuous activation mediated by hyaluronic acid-CD44 generate a remarkable synergistic effect; the dynamic release gradient constructed by the volatile / non-volatile solvent realizes ideal zero-order release kinetics, has excellent effects in the aspects of treatment effect, duration, safety and the like, and provides a brand new non-drug solution for ED treatment.

The application belongs to the technical field of medicine preparation, and particularly relates to a TRPM8 agonist compound and a preparation method and application thereof. The deuterated TRPM8 agonist compound provided by the application has excellent TRPM8 receptor agonist activity, can effectively improve the symptoms of dry eye, significantly promote tear secretion and repair corneal epithelial damage, and has better curative effect than existing classical TRPM8 agonists, and can be used for preparing a medicine for treating dry eye, thereby providing a new effective selection for clinical treatment of dry eye. The deuterated TRPM8 agonist compound provided by the application is prepared by using a four-step synthesis process, raw materials are easy to obtain, process operation is simple, and the reaction process is stable and controllable, and is suitable for industrialized synthesis.

This application relates to the pharmaceutical field, and specifically to a multi-TRP ion channel modulator, its preparation method, and its application. The multi-TRP ion channel modulator developed in this application can inhibit TRPV1, activate TRPM8, and activate TRPA1, and can be used to treat functional gastrointestinal disorders, intestinal mucosal damage, intestinal inflammation, immune dysregulation, gut microbiota imbalance, gastrointestinal tumors, pain, or peripheral neuritis.

The invention discloses an aromatic essential oil composition with a refreshing function, a fragrance rod and preparation methods of the aromatic essential oil composition and the fragrance rod, and the aromatic essential oil composition comprises the following components in percentage by mass: 99.5-99.7% of compound essential oil and 0.3-0.5% of an antioxidant, wherein the compound essential oil is prepared from spearmint essential oil, grapefruit essential oil and tea tree essential oil, and the mass ratio of the spearmint essential oil to the grapefruit essential oil to the tea tree essential oil is (0.5 to 0.8) to (0.19 to 0.49) to (0.01 to 0.05). According to the embodiment of the invention, the golden proportion of spearmint and grapefruit essential oil is innovatively adopted, so that a dual action mechanism is realized: spearmint essential oil activates a peripheral TRPM8 receptor to generate instant cooling feeling, grapefruit essential oil promotes dopamine release to enhance central awakening, tea tree essential oil can inhibit release of central inhibitory neurotransmitters such as GABA (gamma-aminobutyric acid), and tea tree essential oil can promote the release of the central inhibitory neurotransmitters such as GABA (gamma-aminobutyric acid); meanwhile, the herbal cool smell can instantly stimulate nasal mucosa, trigger olfactory awakening reaction and keep the cerebral cortex in a waking state, and the refreshing effect is remarkably better than that of single essential oil through the synergistic effect of the three components.

The invention relates to the field of medicine, in particular to a multi-TRP ion channel regulator and a preparation method and application thereof. The multi-TRP ion channel regulator researched and developed in the invention can inhibit TRPV1, activate TRPM8 and activate TRPA1, and is used for treating functional gastrointestinal diseases, intestinal mucosa injury, intestinal inflammation, immune disorder, dysbacteriosis, digestive tract tumors, pain or peripheral neuritis.

Contact lenses that release a TRPM8 agonist provide a cooling effect that can enhance contact lens comfort. In addition to the TRPM8 agonist, the contact lens or its packaging solution contains a TRPM8 antagonist that attenuates the action of the TRPM8 agonist when the lens is first worn. The TRPM8 antagonist reduces initial unpleasant sensations that may otherwise be caused by the TRPM8 agonist when the lens is first worn.

The application relates to application of anagirine A in preparation of analgesic drugs, and relates to an anagirine A compound separated from anagallis arvensis, which is an analgesic drug with inhibitory effects on transient receptor potential cation channel subfamily M member 8 (TRPM8), voltage-gated potassium channel 1.2 (Kv1.2), voltage-gated potassium channel 1.3 (Kv1.3), transient receptor potential cation channel protein 6 (TRPC6) and voltage-gated calcium channel 2.1 (Cav2.1), and is specifically a drug for neuropathic pain, traumatic pain or inflammatory pain. The compound anagirine A in the application can be combined with multiple analgesic related target points, so that a synergistic effect is generated, the treatment effect is enhanced, and side effects and drug resistance are reduced.

This specification describes modified monoterpene TRPM8 activating compounds. In particular, the compounds provided herein affect the function of ion channels in cells and are useful as therapeutic agents or in conjunction with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions, including inflammatory eye diseases such as uveitis, cardiovascular diseases, inflammatory diseases, and diseases characterized by abnormal growth such as cancer. This specification describes Ca 2+ This is an N-substituted C6 cyclylcarboxamide compound that affects intracellular ion transport, such as ions, and is useful as a therapeutic agent or in combination with one or more additional therapeutic agents.

The application provides a cannabinoid compound, a preparation method and application thereof. The cannabinoid compound has a structure shown in formula (I). The application obtains the cannabinoid compound with the novel structure through an artificial synthesis method, and finds that the cannabinoid compound has a selective inhibitory effect on a TRPM8 channel, so that a theoretical basis and a material basis are provided for further development of the cannabinoid compound as a potential drug.

Disclosed are TRPM8 modulators as defined by formula (I) for achieving a cooling effect on skin and mucousa. The disclosure relates to a particular class of compounds capable to activate TRPM8 ion channels. It further relates to the use of these compounds for inducing a sensation of coldness, and to consumer products comprising these compounds.

Provided is a tobacco product in which a tobacco material itself produces a cooling sensation. A tobacco material derived from a plant body of the genus Nicotiana according to the present disclosure is derived from a plant body of the genus Nicotiana into which a mutation causing suppression of the function of an endogenous JOX gene has been introduced. This tobacco material has a cold-sensitive receptor TRPM8 activity.

A beverage is a drinkable liquid. Described here is a beverage containing a cooling agent that will exert cooling sensations in the upper center of the chest and make a subject feel comfortable. The cooling agent is an agent that targets TRPM8 receptors on nerve cell membranes. The beverage can be imbibed without unpleasant taste and the goal is to make the whole body feel cooler for about 20 min or more after drinking. By choosing the right molecule and right concentration, cooling intensity, location, and duration in the chest is controlled. Surprisingly, the cooling agent was also effective when consumed with warm or hot beverages. The beverage contains selected 1-diisopropyl-phosphinoyl-alkanes and taste-modulating agents selected from sweeteners, extracts from hops, ginger, or cinchona. Various uses of this cooling beverage are proposed.

The present application provides compositions and methods for treating ocular conditions (e.g., dry eye syndrome, dry eye disease, keratoconjunctivitis sicca, inflammatory dry eye, redness, or meibomian gland dysfunction). The compositions can comprise a transient receptor potential melastatin 8 (TRPM8) agonist (e.g., menthol or AR-15512 ((1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexanecarboxamide)) and a semi-fluorinated alkane compound; or can comprise a TRPM8 agonist (e.g., menthol AR-15512 ((1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexanecarboxamide)), a semi-fluorinated alkane compound. The compositions can confer chemical stability of the TRPM8 agonist.