65 results about "Imiquimod" patented technology

The invention relates to application of cembratrienol in preparation of a medicine for preventing and / or treating psoriasis, and belongs to the technical field of biological medicine. The invention provides an application of cembratrienol in preparation of a medicine for preventing / or treating psoriasis. Researches find that cembratrienol can significantly inhibit secretion of inflammatory factors in a psoriasis-like cell model induced by M5; moreover, research finds that cembratrienol can significantly improve the skin lesion condition of an imiquimod-induced psoriasis mouse model, improve the weight loss degree of the psoriasis mouse model, relieve the pruritus condition of the psoriasis mouse model, improve the skin inflammation of the psoriasis mouse model, repair the skin barrier of the psoriasis mouse model, and improve the curative effect of the psoriasis mouse model. The body immune response of the psoriasis mouse model is reduced. Therefore, cembratrienol has a great application prospect in preparation of the medicine for preventing / treating psoriasis.

The invention discloses an application of core proteoglycan or a coding gene thereof as a target spot in preparation of psoriasis treatment drugs, and a series of experiments prove that DCN can effectively protect mouse psoriasis-like dermatitis induced by imiquimod, improve skin scale, erythema, thickening and epidermal abnormal differentiation, enhance the barrier function of skin, improve the curative effect of psoriasis, and improve the curative effect of psoriasis. A large amount of infiltration of inflammatory cells is reduced, and a certain anti-inflammatory effect is achieved. Experimental research shows that the DCN has an obvious drug effect on a psoriasis model, is safe and efficient, has no side effect, is simple in production process and has the potential of realizing medical transformation. And the potential application value of the DCN on other various skin inflammatory diseases can be expanded.

The invention discloses an application of a polypeptide Apelin-13 in a medicine for treating psoriasis, in particular to psoriasis-like skin lesion. In an imiquimod (IMQ) cream induced mouse psoriasis model, intraperitoneal injection of Apelin-13 can significantly reduce scale, erythema and skin thickness, and can inhibit proliferation of epithelial spine cells. HE staining and immunohistochemical staining are carried out on the skin tissue of an experimental mouse, and the result shows that Apelin-13 can reduce the expression of the psoriasis marker protein K17, the thickness of the surface layer of the back side skin of the experimental mouse and the downward extension of a spinous layer. Experimental mouse serum ELISA (enzyme-linked immunosorbent assay) detection results show that the Apelin-13 can be used for down-regulating IL-17A (interleukin-17A) which is highly expressed in psoriasis. The polypeptide Apelin-13 can be used as a medicine for treating psoriasis, especially a medicine for treating psoriasis-like skin lesion.

The present invention belongs to the field of traditional Chinese medicines, and particularly relates to Leixihaokang, a preparation method therefor, and use thereof. The Leixihaokang of the present invention is prepared from the following active pharmaceutical ingredients in parts by weight: 10 parts of Tripterygium glycosides and 0.1-1.3 parts of Artemisia annua extract. According to the present invention, animal experiments prove that the Leixihaokang can ameliorate renal damage in nephrotic syndrome caused by adriamycin, reduce the occurrence of proteinuria, and reduce the apoptosis of renal tissue cells. Meanwhile, the Leixihaokang of the present invention has a good inhibitory effect on renal, hepatic, splenic, and cardiac toxicity in the treatment process of nephrotic syndrome. According to the present invention, animal experiments also prove that the Leixihaokang can ameliorate skin injury in imiquimod-induced psoriasis, reduce inflammatory infiltration and alleviate skin damage. Meanwhile, the Leixihaokang has a certain degree of inhibitory effect on the hepatic and reproductive system toxicity in the treatment process of psoriasis.

The present invention discloses an application of LCE5A as a target in the preparation of a drug for treating inflammatory skin diseases including psoriasis, wherein the LCE5A is mainly expressed on the epidermis; the present invention confirms through a series of experiments that LCE5A can effectively alleviate imiquimod-induced psoriasis-like skin inflammation in mice. The protein can significantly improve the barrier function of mouse skin, inhibit the release of proinflammatory factors and reduce the infiltration of inflammatory cells by regulating the proliferation and differentiation of keratinocytes. This provides important experimental support for the use of LCE5A in the preparation of drugs for skin diseases caused by skin barrier damage, as well as the development of functional skin care products. The experimental results clearly show that LCE5A exhibits significant therapeutic effects in a mouse psoriasis-like inflammation model, and its effect is safe and stable. The protein has a simple extraction and purification process, has good industrial production potential, and lays a solid foundation for clinical application.

The invention provides an application of Cath-HG in preparation of a medicine for preventing and / or treating psoriasis. Experiments prove that Cath-HG has a good curative effect on an imiquimod-induced mouse psoriasis model, can improve skin injury, reduce PASI score, reduce inflammatory cytokine mRNA level, reduce spleen coefficient, recover the number of platelets and neutrophils, inhibit platelet activation and platelet-neutrophil compound formation, reduce neutrophil infiltration and activation, and can be used for treating psoriasis. The release of extracellular traps of neutrophils is inhibited.

The invention belongs to the technical field of biological medicines, and relates to an application of beta-guanidinopropionic acid (3-Guanidinopropionic acid, beta-GPA) in preparation of a medicine for treating chronic inflammatory dermatosis. The invention discovers that the creatine transporter SLC6A8 is remarkably and highly expressed in skin lesion tissues of psoriasis for the first time, and the protein is strongly associated with occurrence and development of chronic inflammatory skin diseases such as psoriasis. The SLC6A8 transporter inhibitor beta-guanidino propionic acid can obviously inhibit the expression level of keratinocyte inflammatory factors, and meanwhile, the imiquimod-induced psoriasis model mouse skin lesion symptom is reversed, so that the beta-guanidino propionic acid has the effect of resisting psoriasis. The invention can provide new therapeutic targets and new drug choices for psoriasis and other chronic inflammatory skin diseases.

The invention discloses an indoline derivative and application thereof. According to the invention, the regulation effect of the derivative on the chemotaxis and secretion functions of ILC3 is evaluated; it is found that the derivative has a promoting effect on chemotaxis of ILC3 to an inflammatory site and up-regulation of IL-22 expression, has very remarkable effects on mouse ulcerative colitis (UC) induced by DSS, mouse Crohn disease (CD) induced by TNBS, acute lung injury induced by lipopolysaccharide (LPS), mouse psoriasis induced by imiquimod and other diseases in vivo, and is superior to existing clinical treatment drugs. Good development and application prospects are realized.

The invention discloses an application of sarcandra glabra polysaccharide in preparation of a medicine for preventing and / or treating psoriasis and delaying relapse of psoriasis. The glabrous sarcandra herb polysaccharide can relieve inflammation caused by psoriasis, reduce expression of memory T cells at skin lesions of a psoriasis recurrence model mouse and relieve psoriasis symptoms of the recurrence model mouse. The invention finds that the glabrous sarcandra herb polysaccharide can obviously improve the skin injury degree of an imiquimod (imiquimod, IMQ) interval induced psoriasis recurrence model mouse, reduce the skin erythema, thickening and scale of the IMQ interval induced psoriasis recurrence model mouse, and reduce the expression of memory T cells at the skin injury part of the psoriasis recurrence model mouse, so that the glabrous sarcandra herb polysaccharide can be used for treating the psoriasis. The glabrous sarcandra herb polysaccharide has great application prospects in preparation of the medicine for preventing / treating the psoriasis, and especially can relieve recurrence symptoms of the psoriasis.

Some aspects of the present disclosure are generally related to injectable compositions, for example, for intratumoral drug delivery. In some embodiments, the injectable composition comprises a polymer configured to undergo a solution-gel transition when heated from room temperature to at or around body temperature, allowing for the injection of the injectable composition as a liquid with subsequent gelation to retain the composition at the injection location. In some embodiments, the injectable compositions may be capable of encapsulating radio-opaque label and / or a hydrophobic immunoadjuvant (e.g., imiquimod) at a concentration of greater than or equal to 0.5 mg / mL. Accordingly, some aspects of the present disclosure are related to the radio-opaque label facilitating visualization of the injectable composition during injection and / or the retention of the injectable composition at the injection location, allowing for localized and extended-release of the immunoadjuvant. Still other aspects are generally directed to related methods, kits, or the like.

The invention belongs to the technical field of biology, and relates to application of isovaleric acid in treatment of psoriasis. In order to solve the problems that existing psoriasis treatment drugs (such as biological agents) have side effects, the curative effect is reduced, and relapse occurs after drug withdrawal, the invention provides a psoriasis treatment scheme taking isovaleric acid as an active component, and the imiquimod-induced psoriasis-like skin lesion can be remarkably relieved by locally smearing the isovaleric acid with the concentration of 2mM; the epidermis excessive proliferation and the expression of inflammatory factors such as IL-17A, IL-17F and CXCL1 are reduced. The isovaleric acid disclosed by the invention is a small molecule compound, is simple to prepare, convenient to administrate and high in safety, fills the application blank of the isovaleric acid in the field of psoriasis treatment, and provides a new effective way for psoriasis treatment.

The present invention provides a method for detecting bacterial endotoxins in drugs containing a quinoline ring structure, and relates to the technical field of bacterial endotoxin detection. Specifically comprising the following steps: first dissolving a drug containing a quinoline ring structure with a solvent to obtain a test sample stock solution to release bacterial endotoxins in the drug; then diluting the stock solution to reduce the interference of the drug's own properties on bacterial endotoxins; and finally detecting bacterial endotoxins by dynamic colorimetry. Wherein, the solvent is N, N-dimethylformamide with a volume fraction of 60-70%; the drug containing a quinoline ring structure includes imiquimod; the test sample stock solution concentration is 0.1-10 mg / ml, and the stock solution dilution multiple is 10-1000 times. The technical solution provided by the present invention solves the problem that drugs containing a quinoline ring structure in the prior art are insoluble in water, and effectively improves the accuracy of detecting the bacterial endotoxin content of drugs containing a quinoline ring structure. Moreover, the conventionally adopted gel method is avoided, thereby solving the problem of false negative results of taking the supernatant and detecting it by gel method.

The invention discloses an application of a piperazine amide derivative in preparation of a medicine for treating psoriasis, and belongs to the field of biological medicine, the piperazine amide derivative has the following structure: # imgabs0 # in a mouse psoriasis model induced by imiquimod cream, the scale, erythema and skin thickness can be obviously reduced by oral administration and local application of ID230301A-1, and the application of the ID230301A-1 in the mouse psoriasis model induced by imiquimod cream can be promoted. The hyperplasia of epithelial spine cells can be inhibited. Immunoblotting analysis is carried out on the skin tissue of an experimental mouse, and the result shows that the ID230301A-1 can regulate and control the expression of STAT3 signal related protein. Therefore, the medicine can be used as an active ingredient for regulating metabolism to prepare a medicine for treating psoriasis.

The invention discloses a double-target inhibitor with anti-psoriasis activity, and the structural general formula of the double-target inhibitor is shown in the specification. The double-target inhibitor with anti-psoriasis activity provided by the invention has good efficacy on in-vitro anti-psoriasis related tests and in-vivo imiquimod induced mouse models; the compound B5e shows better anti-psoriasis activity than their parent drugs and combined administration of the parent drugs.

The invention belongs to the field of medicines, and particularly relates to a quinonoid diterpenoid compound, a preparation method thereof and application of the quinonoid diterpenoid compound in treating psoriasis. The synthetic raw materials are easy to obtain, the steps are simple, the reaction is easy to control, and the method has important reference and practical values for preparing quinonoid diterpenoid compounds on a large scale. The prepared compound 5 (LZY-15) has remarkable AhR agonist activity. The drug effect of the compound 5 (LZY-15) on skin inflammation psoriasis is explored through animal experiments, and the compound 5 (LZY-15) can obviously relieve squamation and skin thickening of psoriasis-like skin lesion local parts induced by imiquimod and improve the pathological score of psoriasis; the contents of leucocytes, monocytes and neutrophils in peripheral blood of mice can be obviously reduced, and the inflammation level of the mice is reduced; in addition, the traditional Chinese medicine composition can also obviously improve cuticle pathological changes such as hyperkeratinization and incomplete keratinization, epidermal pathological changes such as spinous skin thickening and granular layer disappearance, and changes such as corium papillary extension caused by imiquimod induction.

The invention relates to the technical field of animal model construction, in particular to a psoriasis cardiovascular co-disease mouse model and a construction method thereof. The invention provides a construction method of a psoriasis cardiovascular disease mouse model, which comprises the following steps: feeding a mouse with high fat diet for 5-7 weeks, and injecting a streptozotocin solution for 2-4 days; after the mouse is fed with high-fat diet for 14-16 weeks, imiquimod is smeared on the mouse for 6-8 days, and the psoriasis cardiovascular disease mouse model is obtained. According to the invention, a novel metabolic disorder aggravated psoriasis cardiovascular co-disease mouse model is successfully constructed, and a solid foundation is laid for mechanism exploration of later psoriasis cardiovascular co-disease.

The invention discloses an application of a CD177 targeted membrane modified liposome in preparation of a medicine for preventing and / or treating systemic lupus erythematosus. The structure of the CD177 targeting membrane modified lipidosome is divided into three layers, and comprises a lipidosome loaded with a PADI4 inhibitor, a targeting recognition layer formed by coupling CD177 targeting peptide on the surface of the lipidosome, and a bionic functional layer formed by coating a natural neutrophile granulocyte membrane on the outermost layer. In an imiquimod (IMQ)-induced lupus model, the medicine treatment shows strong disease remission capability: 1) improving the whole body phenotype: obviously reducing the swollen spleen and lymph node of lupus mice; 2) repairing kidney functions: significantly relieving glomerulonephritis, and reducing inflammatory cell infiltration and IgG and complement C3 deposition in glomerulus, and 3) significantly reducing the level of proinflammatory cytokines in serum and the titer of a lupus marker anti-dsDNA antibody.

The application belongs to the technical field of animal model construction, and particularly relates to a construction method of a stress-aggravated psoriasis mouse model and application. The construction method comprises the following steps: (1) shaving the back of the mouse, placing the mouse in a 50-milliliter breathable centrifuge tube, and limiting the activity for four hours; (2) taking out the mouse, and waiting for the back skin to dry; (3) uniformly applying imiquimod cream to the back of the mouse, and placing the mouse back into the cage; and (4) repeating the above steps every day until the stress-aggravated psoriasis mouse model is successfully constructed. The construction method can quickly and simply construct the stress-aggravated psoriasis mouse model for subsequent research.

The invention discloses a stilbene derivative, a preparation method thereof and application of the stilbene derivative in preparation of drugs for treating psoriasis or ulcerative colitis, and belongs to the technical field of biological medicines. The compounds II-2 and II-23 provided by the invention are used for targeted excitation of AHR related pathways, promotion of AHR nucleation, reduction of secretion of related cytokines at a cellular level, and substantial improvement of mouse skin symptoms and PASI scores of an imiquimod-induced mouse psoriasis model, compared with a lead compound benvimod, the compounds II-2 and II-23 have better psoriasis resistance activity and lower toxicity, and can be used for preparation of drugs for treating psoriasis. Meanwhile, the compound II-23 is found to be capable of effectively treating mouse ulcerative colitis, reducing inflammatory response and improving colitis symptoms. The compound can be used for preparing medicines for treating psoriasis and ulcerative colitis.

The application discloses a Bifidobacterium breve capable of relieving psoriasis and an application thereof, and belongs to the technical field of microorganisms. The application screens a Bifidobacterium breve CCFM683, and the Bifidobacterium breve CCFM683 has the effect of relieving psoriasis caused by imiquimod, which is specifically embodied in the following aspects: (1) significantly reducing the weight loss of psoriasis mice; (2) significantly improving the pathological characteristics such as scales, thickening and redness of the skin of psoriasis-like mice; (3) regulating the level of skin immune factors of psoriasis-like mice; and (4) significantly inhibiting the proliferation of keratinocytes of the skin of psoriasis mice. The Bifidobacterium breve CCFM683 has great application prospect in the preparation of food or medicine for preventing and / or treating psoriasis.

The invention discloses a piperine-based pseudo-natural dimer amide alkaloid compound 1 and a piperine-based pseudo-natural dimer amide alkaloid compound 2 as well as a preparation method and medical application thereof. Dimerization of piperine is realized through a visible light catalytic reaction system Ir (ppy) 3 / 465nm LED, and optically pure enantiomers 1a / 1b and 2a / 2b are obtained through acetonitrile-water system preparative HPLC separation and purification in combination with a chiral chromatographic resolution technology. HRESIMS, multi-dimensional NMR and X-single crystal diffraction confirm that the structure of the compound has a unique cyclohexene skeleton and a bis-piperidyl structure. A biological activity research shows that the target compound has a remarkable inhibition effect on LPS-induced RAW264.7 macrophage NO release, the compound 1 shows an excellent curative effect in an imiquimod-induced psoriasis mouse model, and the effect of the compound 1 is superior to that of a positive drug benvitimod. The invention provides a green and efficient photocatalytic synthesis method, and the obtained compound provides candidate molecules for developing multi-target anti-psoriasis drugs.

The invention discloses an application of a novel peptide UPCP in preparation of a medicine for treating and / or preventing psoriasis. Belongs to the technical field of biological medicine. The application discloses the treatment effect of the novel peptide UPCP on psoriasis for the first time, and researches find that the novel peptide UPCP can effectively relieve symptoms of a psoriasis model induced by LSP, TNF alpha and M2 in an in-vitro cell experiment, significantly down-regulate the expression level of psoriasis cell markers, significantly reduce the transcriptional level of psoriasis-related inflammatory factors, and improve the psoriasis treatment effect. The condition of excessive proliferation of HaCaT cells is effectively reduced. In in-vivo experiments, psoriasis symptoms such as skin desquamation, hyperplasia, erythema, thickening and splenomegaly of an imiquimod-induced psoriasis mouse model can be effectively relieved, the effect of treating psoriasis is achieved, and a new theoretical basis and intervention means are provided for clinical treatment of psoriasis.

The present invention discloses a method for constructing an animal inflammatory model of psoriasis with different severities of skin lesions, comprising the following steps: raising 30 Balb / C mice according to a standard feeding method; weighing and calculating the body surface area of ​​each mouse at baseline D0, and removing the hair of the mice; randomly dividing the 30 Balb / C mice into three groups according to the lesion area, namely a mild group, a moderate group and a severe group; using 5 mg / cm 2 Imiquimod was evenly applied to the lesion area of ​​each mouse; the mice were killed after 7 days of intervention, and the skin tissue and spleen of the mice were taken for subsequent examination. The changes in the skin lesions of the mice were recorded by taking photos with a camera. After 7 days of treatment with imiquimod cream, typical psoriasis-like lesions appeared. The constructed psoriasis animal model has very similar clinical symptoms to psoriasis patients, can show psoriasis-related histological changes and immune system changes, and can be used to screen psoriasis treatment drugs.

The application discloses a method for establishing a psoriasis animal model. The method for establishing the psoriasis animal model is realized by injecting cytokines and applying imiquimod cream externally. The model is characterized by the severity of skin lesions, histopathological changes of skin lesions, expression of CD4 + and CD8 + T cells in immunohistochemistry of skin lesions, and the level of serum inflammatory factors, and conforms to the characteristics of psoriasis. Compared with the model induced by imiquimod cream alone, the model has the advantages of faster occurrence and development of psoriasis, more obvious characteristics of the model, higher stability of the model, longer maintenance time of the model, more diversified mechanisms of the model, and reduced systemic immune response. The model established by the application is simple and easy to operate, and can be widely popularized and applied, and provides an experimental tool for the research and development of the pathogenesis and drugs of psoriasis.

The invention discloses a composite hydrogel with a redox bidirectional regulation function and a preparation method and application thereof, and belongs to the field of biomedical materials.According to the composite hydrogel, polyvinyl alcohol and carboxymethyl chitosan serve as gel matrixes, crosslinking of the two matrixes is achieved through genipin by means of the action of hydrogen bonds and amido bonds, and the composite hydrogel with the redox bidirectional regulation function is obtained. The hydrogel network is loaded with chlorella capable of removing active oxygen components and Ag (at) ZnO capable of generating the active oxygen components. According to the hydrogel, the ROS level can be indirectly regulated and controlled by regulating and controlling the illumination condition, so that potential balance between oxidative stress resistance and ROS accumulation is realized. The hydrogel is locally fed to an imiquimod-induced psoriasis mouse model, a good anti-psoriasis treatment effect is obtained, and it is proved that the hydrogel can effectively resist local skin lesion of psoriasis in a multifunctional, non-irritant and non-invasive mode.

The invention discloses application of an FBXO45 inhibitor in preparation of a medicine for treating psoriasis, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the specific high expression of the FBXO45 in skin lesion tissues of psoriasis patients and imiquimod-induced mouse model skin lesion is found for the first time, and the phenotypes (such as epidermal thickening, inflammatory factor expression and immune cell infiltration) of the psoriasis can be obviously relieved by specifically knocking out the FBXO45 from the skin, so that the FBXO45 is proved to be a potential therapeutic target of the psoriasis. Through virtual screening and molecular docking based on an FBXO45 protein structure, it is found that CD437 can be specifically combined with FBXO45, and the substrate recognition function of the FBXO45 is inhibited. In-vitro experiments show that the CD437 can inhibit the expression level of FBXO45 protein in HaCaT cells, reduce the expression of inflammatory factors such as TNF-alpha and the like, and induce cell apoptosis; in an imiquimod-induced mouse model, the skin lesion symptom (such as reduction of PASI score and reduction of epidermal thickness) is remarkably relieved through local external application of CD437. Therefore, the invention provides a novel FBXO45-targeted small molecule treatment strategy for the psoriasis.

The invention discloses a compound with anti-psoriasis activity and double-target inhibition, and the structural general formula of the compound is shown in the specification. The compound with anti-psoriasis activity and double-target inhibition provided by the invention has good efficacy on in-vitro anti-psoriasis related tests and in-vivo imiquimod induced mouse models; the compound H7e shows better anti-psoriasis activity than their parent drugs and combined administration of the parent drugs.

The invention discloses an application of total glucosides of paeony in treatment of psoriasis in combination with Jikukiespecially and calcipotriol, and relates to the technical field of medical treatment, a psoriasis-like mouse model induced by imiquimod is established, and the synergistic treatment effect of a triple therapy of total glucosides of paeony, Jikukiespecially and calcipotriol is verified; the application comprises the step of jointly applying the three medicines according to a specific dosage. The triple therapy can improve erythema, scale and infiltration symptoms of psoriasis-like skin lesion, effectively reduce the area and severity index score of psoriasis, and inhibit the protein and mRNA expression level of key proinflammatory cytokines in skin lesion tissues; compared with a single drug or a combination of two drugs, the triple therapy provided by the invention shows a better treatment effect, and a new and effective drug combination scheme is provided for clinical treatment of psoriasis.

The invention discloses application of a silicon dioxide nanosphere drug delivery system in drug preparation. The silicon dioxide nanosphere drug delivery system is constructed by silicon dioxide nanoparticles with surface spines, and the silicon dioxide nanoparticles are nanospheres which take silicon dioxide as a matrix, have solid cores of 80-120 nanometers and are coated with hard spines of 40-60 nanometers and are used for delivering RNA to a target part through skin or mucous membranes. Imiquimod is used for inducing a psoriasis mouse model, it is proved that a silicon dioxide nanosphere drug delivery system can deliver small nucleic acid RNA to epidermis and dermal cells, the pharmacological action is achieved, then the silicon dioxide nanosphere drug delivery system is used for treating diseases such as psoriasis, skin cancer, HPV virus infection or androgenetic alopecia, and the wide market application prospect is achieved.

The invention relates to a method for constructing a heterozygote mouse model with IL-1f9K124A point mutation. The method comprises the following steps: step 1, acquiring Cas9mRNA (messenger ribonucleic acid), gRNA (guide ribonucleic acid) and oligo donor DNA (deoxyribonucleic acid); step 2, carrying out micro-injection on the Cas9mRNA, the gRNA and the oligo donor DNA obtained in the step 1 into a fertilized egg male pronucleus of a C57BL / 6J mouse, transplanting the fertilized egg after injection into the uterus of a pseudopregnant female mouse, and inoculating the born mouse in such a way as an F0-generation mouse; 3, performing genotype identification on the F0-generation mice through PCR amplification and sequencing, mating the identified F0-generation positive mice with C57BL / 6J mice, and breeding to obtain F1-generation mice; 4, performing genotype identification on the F1-generation mice through PCR amplification and sequencing to obtain F1-generation positive mice which are IL-1f9K124A point mutation heterozygote mice which can be stably inherited; and 5, carrying out imiquimod induction on the heterozygote mouse with IL-1f9K124A point mutation obtained in the step 4 to obtain the psoriasis mouse model. Compared with the prior art, the invention has obvious progress.