63 results about "Retinoic acid" patented technology

The invention discloses a mannose modified liposome gel microsphere oral delivery system based on cations and application of the mannose modified liposome gel microsphere oral delivery system. The oral delivery system comprises a core layer and a wrapping layer, the core layer is mannose modified cationic liposome loaded with a mucous membrane adjuvant retinoic acid and an antigen, and the wrapping layer is sodium alginate gel vulcanized and modified by cysteine. The mannose modified cationic liposome is prepared by coupling mannose on the surface of the cationic liposome, and the cysteine modified sodium alginate gel is used for protecting antigens in the core layer from being eroded by gastric juice, enhancing the adhesiveness of a delivery system in the intestinal tract and prolonging the retention time of the delivery system in the intestinal tract; in addition, the R-MLip can be expanded and released under the environment that the pH of the intestinal tract is increased. The inside of the gel microsphere of the oral delivery system shows a regular net-shaped structure and has abundant holes and channels, and the oral delivery system shows a good prospect in the aspect of enhancing mucous membrane and systemic immunity and possibly becomes a potential substitute of a traditional attenuated live vaccine in the future.

The invention relates to the technical field of biomedicine, in particular to a novel target spot for resisting chikungunya virus infection and application. According to the invention, human colon cancer cells (HCT116) are taken as target cells, and retinoic acid-induced protein expression of the target cells is reduced by adopting a gene knockout technology, so that host factors capable of effectively inhibiting CHIKV infection of the human colon cancer cells are found, and the purpose of blocking CHIKV infection from the source is achieved. It is found that retinoic acid induced protein 16 (RAI16) plays an important role in CHIKV infected HCT116 cells, and CHIKV infection can be obviously promoted by down-regulating expression of RAI16. The invention provides an application of RAI16 in preparation of a medicine for preventing or treating chikungunya virus infection, and provides a new target spot and a treatment scheme for clinically preventing and treating fever, arthralgia, arthrocele, muscular pain, headache, nausea, fatigue, rash and other diseases caused by CHIKV infection.

The present application relates to the technical field of cosmetic raw materials, and provides tocopheryl retinoate and application thereof in cosmetics and / or skin care products. The tocopheryl retinoate introduces a tocopherol group with antioxidant activity into the molecular structure of retinoic acid, significantly improves the light stability and thermal stability of the compound while maintaining the biological activity of vitamin A ingredients, and effectively reduces the irritation to the skin. The tocopheryl retinoate is suitable for the cosmetic and / or skin care product system used in the daytime, can improve the skin condition, repair the skin barrier and protect the skin, and has good safety and wide application prospect.

The present invention provides a retinoic acid derivative that has high stability and water solubility. The present invention relates to a carboxylic acid ester compound of trehalose or a derivative thereof and retinoic acid.

The present invention relates to a conjugate compound comprising 13-cis-retinoic acid and vitamin C, and its pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier. The present compound has a much better water solubility than that of retinoic acid, and thus reduces an effective dosage of retinoic acid and minimizes side effect. The present compound increases the efficiency and concentration of 13-cis-retinoic acid to across the cell membrane into the cell. The present compound is useful in treating cancer such as pancreatic cancer.

The invention provides a special culture medium for prostate cancer organoid and a culture method thereof, and belongs to the technical field of biological medicines. The special culture medium for the prostatic cancer organoid is composed of a basic culture medium and a culture additive, and the basic culture medium does not contain exogenously added Noggin recombinant protein and R-spondin recombinant protein. The culture additive is prepared from a basic fibroblast growth factor, a keratinocyte growth factor, a fibroblast growth factor 10, insulin, a p38MAPK signal channel inhibitor, an insulin-like growth factor 1, B27, nicotinamide, N-acetylcysteine, hydrocortisone, a ROCK kinase inhibitor, retinoic acid, interleukin 6, prostaglandin E2, a eriocin and androgen. According to the special culture medium for the prostatic cancer organoid, the culture success rate is increased while the cost is reduced.

The invention provides a drug-loaded gelatin nanogel, a bionic nanogel, a preparation method of the drug-loaded gelatin nanogel, a preparation method of the bionic nanogel, a combined drug and application of the bionic nanogel, and belongs to the technical field of biological medicine. According to the invention, all-transretinoic acid, pirfenidone and gelatin react to form drug-loaded gelatin nanogel, and the drug-loaded gelatin nanogel can synergistically inhibit the activation of pancreatic stellate cells and block a fibrosis-promoting signal channel, so that the reversion of a pancreatic cancer fibrosis microenvironment is realized; meanwhile, the activated pancreatic stellate cell membrane is coated with the drug-loaded gelatin nanogel to construct the bionic nanogel, so that the bionic nanogel has active targeting property, and the delivery efficiency and the treatment effect of the drug are remarkably improved; and the drug-loaded gelatin nanogel, the bionic nanogel and the chemotherapeutic drug are combined for treating pancreatic cancer, so that a remarkable anti-tumor effect is achieved, and the combined treatment of the bionic nanogel and gemcitabine has a synergistic anti-tumor effect. The gel provided by the invention realizes effective regulation and control of a pancreatic cancer dense fibrosis microenvironment, and provides a feasible new strategy for treatment of pancreatic cancer.

The invention discloses an application of an activator combined by one or more genes / proteins in preparation of drugs for treating hypertrophic scars, and belongs to the technical field of biological medicines. In order to solve the problem that when retinoic acid cream is used for preparing hypertrophic scars, a specific mode and an action target of a retinoic acid signal channel for regulating and controlling fibroblasts are not disclosed yet, the action target and a regulation and control mechanism of ATRA for regulating and controlling fibroblast activation and glucose metabolism remodeling are explored through in-vivo and in-vitro experiments; and on the basis of a Cre-loxP system, the function of the target gene is verified. Researches in the invention show that ATRA promotes transcription of HIC1 and inhibits transcription and expression of TGF-beta1 by activating RAR alpha on one hand, and ATRA promotes transcription of HIC1 and inhibits transcription and expression of TGF-beta1 on the other hand; on the other hand, the transcription of PCK1 and PCK2 is promoted, so that the proliferation and abnormal activation of HSFs are reduced, and the occurrence and development processes of hypertrophic scars are finally inhibited. The conclusion provides a sufficient theoretical basis for inhibiting hypertrophic scar formation by ATRA.

The present application relates to a culture medium for the culture of intestinal organoids characterized in that it comprises neuregulin 1 (NRG1) and all-trans retinoic acid (atRA). It also relates to a method using this medium to culture intestinal organoids.

Provided herein are novel reprogrammed smooth muscle cells (rSMCs) and methods of making and using the cells for the treatment of ischemia. The rSMCs are produced by culturing a fibroblast with an all-trans-retinoic acid (ATRA) under conditions that produce the rSMC from the fibroblast, wherein the fibroblasts are genetically modified to overexpress myocardin. The rSMCs offer advantages over currently available regenerative vascular therapies by promoting vascular perfusion in a recipient subject. In particular, the rSMCs can increase neovascularization of both small and large vessels.

This invention discloses a solvate of rememega-2 and its preparation method. The rememega-2 solvate (compound II) provided by this invention has a purity of up to 99.15% compared with the existing rememega-2 methyl tert-butyl ether solvate. The preparation method includes the following steps: adding crude rememega-2 to a binary solvent, heating to 45℃~75℃, adding an antisolvent, stirring, crystallizing, cooling and filtering, and drying under reduced pressure to obtain rememega-2 solvate (compound II). Then, placing rememega-2 solvate (compound II) in ethanol and stirring to obtain rememega-2 (compound I). This route is simple to operate, the process is stable, and it is easy to scale up. Moreover, the rememega-2 (compound I) prepared by this solvate (compound II) has a purity of up to 99.66%, which is higher than that of rememega-2 (compound I) prepared by the existing rememega-2 methyl tert-butyl ether solvate. It also has better fluidity, does not caking, is easy to transfer, and is convenient for later production.

This invention discloses a method for synthesizing an intermediate of retinoic acid, relating to the field of pharmaceutical organic synthesis technology, comprising the following steps: S1, in the presence of a base, 2-amino-3-chloropyridine and 4-bromopiperidine undergo a nucleophilic substitution reaction in solvent A to prepare compound III; S2, in the presence of a catalyst and ammonia solution, compound III undergoes an amination reaction in solvent B to prepare compound II; S3, compound II is dissolved in solvent C, and sequentially undergoes CDI cyclization and hydrogen chloride solution salt formation to prepare compound I, namely 1-(piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one. This invention is low-cost, uses mild reaction conditions, has a simple synthesis process, high yield, and eliminates the need for expensive and potentially unsafe excipients, effectively improving reaction safety, being environmentally friendly, and suitable for industrial production.

This invention, entitled "A Method and Product for Pretreatment of Mesenchymal Stem Cells and Its Application in Stroke Drugs," belongs to the field of biotechnology. The technical problem to be solved is to improve the function and therapeutic effect of mesenchymal stem cells. The key technical solution is a method for pretreatment of mesenchymal stem cells, including: culturing cells using an activation medium, culturing cells using a directional medium, and culturing cells under hypoxic conditions using an adaptation medium; the activation medium contains complete medium, IFN-γ, TNF-α, and IL-1β; the directional medium contains complete medium, sodium valproate, 5-azacytidine, and all-trans retinoic acid; the adaptation medium is a complete medium containing basal medium and free of animal serum. The pretreatment method of this invention enhances the anti-inflammatory, neuroprotective, and angiogenic capabilities of mesenchymal stem cells, showing significant therapeutic effects on stroke, and since it does not use animal serum, it meets clinical requirements.

Disclosed are methods of accelerating development of new hair follicles in pluripotent stem cell-derived skin organoids. In particular, disclosed are methods of accelerating development of new hair follicles in skin organoids by adding one or more growth factors, such as FGF10, FGF20, BIO, ruxolitinib, tofacitinib, LDN193189, vitamin E, GDNF, retinoic acid, or IGF2. The growth factors are added to a culture of skin organoid at critical windows of time of the skin organoid development, such as after (or upon) the formation of epidermis and dermis in the skin organoid.

The present invention relates to a composition for preventing or treating autoimmune diseases. In particular the present invention relates to a composition that prevents or treats the disease by specifically targeting the immune cells responsible for the autoimmune reaction. Thus one aspect relates to a composition comprising DDA and TDB or MMG, retinoic acid or analogues thereof, and at least one autoimmune antigen for use in prevention or treatment of autoimmune diseases.

The invention relates to the technical field of animal growth regulation, in particular to application of all-trans retinoic acid in regulation of oxidation resistance and digestion and metabolism capacity of Ningxiang pigs. According to the application, all-trans-retinoic acid is added into the Ningxiang pig feed, and the research on the antioxidant capacity of intestinal microorganisms and serum of the Ningxiang pig feed shows that all-trans-retinoic acid can improve the antioxidant capacity of the Ningxiang pig by enhancing the total antioxidant capacity of the Ningxiang pig, changing the diversity of intestinal flora of the Ningxiang pig and changing microbial metabolites and metabolic pathways of the intestinal flora; the biosynthesis and metabolism of amino acids are promoted, so that the oxidation resistance and digestion and metabolism capabilities of the Ningxiang pigs are enhanced.

The application discloses a kind of serum-free epidermal melanocyte culture medium and its application, method includes by dissolving adenine, hepatocyte growth factor (HGF), glutamine, retinoic acid, vitamin E, nicotinic acid, sodium selenite, sodium hyaluronate and recombination human type XVII collagen are configured into initial culture medium;Preparation of melanocyte stimulating hormone, endothelin-3, transferrin, triiodothyronine, cholesterol, neuroregulin 1 (NRG1), 3-isobutyl-1-methyl purine (IBMX), dibutyryl cyclic adenosine monophosphate (db-cAMP), cholera toxin, hydrocortisone and recombination human insulin mother liquor;Step three: according to culture and concentration, a certain amount of mother liquor of step two is added to initial culture medium.The culture medium can effectively promote human epidermal melanocyte proliferation, melanin accumulation and help to promote human umbilical cord mesenchymal stem cells into human epidermal melanocyte, provide key advantage for obtaining functional melanocyte with high activity and therapeutic potential.

The invention belongs to the technical field of biological medicines, and particularly relates to all-trans retinoic acid phospholipid complex nanoparticles as well as a preparation method and application thereof. The invention relates to sialic acid derivative modified all-trans retinoic acid and phospholipid compound nanoparticles. The sialic acid derivative modified all-trans retinoic acid and phospholipid compound nanoparticles comprise sialic acid derivatives, all-trans retinoic acid and phospholipid, wherein the sialic acid derivative accounts for 5-40% of the total mass of the phospholipid, and the drug-lipid molar ratio of all-trans retinoic acid to the phospholipid is (1: 4)-(1: 10). According to the sialic acid derivative modified all-trans retinoic acid phospholipid complex nanoparticles, the problem that all-trans retinoic acid is poor in solubility is solved, the bioavailability of an existing all-trans retinoic acid oral product is improved, the tumor inhibition effect of all-trans retinoic acid in solid tumors is improved, and the bioavailability of all-trans retinoic acid is improved. And the drug resistance of all-transretinoic acid in solid tumors is overcome. The nano preparation is simple and convenient in process, high in reproducibility and convenient for industrial production. In addition, a combined treatment strategy of the nano preparation and a low-dose chemotherapeutic drug shows a very excellent synergistic effect, which is shown as a tumor healing condition.

The invention discloses application of retinoic acid or a derivative thereof in preparation of a medicine for promoting healing of a tooth extraction wound. It is found that retinoic acid can promote proliferation of mesenchymal cells in the tooth extraction wound and differentiation of hard tissue, so that rapid healing of the tooth extraction wound is promoted, the healing period of the tooth extraction wound is shortened, and early complications of healing of the tooth extraction wound are reduced.

A retinoic acid-alcohol amine complex has retinoic acid and an alcohol amine compound. The complex is in liquid form at room temperature, has good water solubility / water dilution resistance and good skin penetration effect.

The application provides an iPS-driven nasopharyngeal epithelial organoid and a preparation method and application thereof. The preparation method comprises the following steps: differentiating humanized iPS cells into endoderm cells; wrapping the endoderm cells with Matrigel and then placing the endoderm cells in DMEM / F-12 culture medium containing Dorsomorphin and SB431542 for culture to obtain foregut organoids; culturing the foregut organoids in DMEM / F-12 culture medium containing FGF10 protein, CHIR-99021, retinoic acid and BMP4 protein to obtain airway epithelial progenitor cell organoids; and culturing the airway epithelial progenitor cell organoids in DMEM / F-12 culture medium containing FGF10 protein, retinoic acid and BMP4 protein to obtain nasopharyngeal epithelial organoids. The iPS cells are continuously differentiated in multiple stages by using culture medium containing different inducers, and the nasopharyngeal epithelial organoids are mass-produced.

This invention provides a circRNA-LNP delivery system for in vivo induction of iTregs, its preparation method, and its applications. The delivery system includes circRNA encoding human TGF-β1, lipid nanoparticles encapsulating the circRNA, and IL-2 modified on the surface of the lipid nanoparticles. This invention synergistically combines retinoic acid as a functional immunomodulatory small molecule with five lipids, significantly improving the uptake efficiency of Treg precursor cells and the induction efficiency of iTregs. It can also efficiently increase the proportion of functional iTregs in diseased tissues in vivo, demonstrating excellent therapeutic effects on immunomodulatory diseases such as ulcerative colitis, and providing a novel technical pathway for the radical treatment of autoimmune and inflammatory diseases.

The invention relates to the technical field of drug delivery, in particular to an all-transretinoic acid prodrug material, a drug-loaded micelle as well as a preparation method and application of the all-transretinoic acid prodrug material and the drug-loaded micelle. The all-trans retinoic acid prodrug material comprises an all-trans retinoic acid polyethylene glycol chain segment, wherein the all-trans retinoic acid polyethylene glycol chain segment is a linear chain segment formed by all-trans retinoic acid and a polyethylene glycol chain segment in a chemical coupling manner; the all-trans retinoic acid polyethylene glycol chain segment has tumor environment responsiveness and can be subjected to chain scission in a tumor environment and release all-trans retinoic acid; the tumor environment comprises one or more of an esterase environment, a reducing environment, an acid environment, an active oxygen environment and a low-oxygen environment. The all-trans retinoic acid prodrug material and the drug-loaded micelle have the capability of breaking bonds in a tumor environment, are not easy to metabolize and degrade, have good deep permeability to tumors and high release efficiency, and can realize better drug delivery and treatment effects.

Provided are a pharmaceutical combination and the use thereof in the treatment of acne. The pharmaceutical combination contains an antiandrogen, a retinoic acid drug and an antibacterial drug. The pharmaceutical combination has a synergistic effect in the treatment of acne.

Provided is a compound or its pharmaceutically acceptable salt, and its pharmaceutical composition, comprising retinoic acid conjugated to carbohydrate.In addition, provided is the use of the compound or its pharmaceutically acceptable salt, or its pharmaceutical composition in the manufacture of a medicament for inhibiting viral infection or replication, or for treating cancer.

The application provides a drug-loaded gelatin nanogel, a biomimetic nanogel and a preparation method and combined drug and use thereof, and belongs to the technical field of biological medicines.The application forms a drug-loaded gelatin nanogel by reacting all-trans retinoic acid with pirfenidone and gelatin, cooperatively inhibits the activation of pancreatic stellate cells and blocks the pro-fibrosis signal pathway, realizes the reversal of the fibrosis microenvironment of pancreatic cancer, coats the drug-loaded gelatin nanogel on the membrane of activated pancreatic stellate cells to construct a biomimetic nanogel, so that the biomimetic nanogel has active targeting, and the drug delivery efficiency and the treatment effect are significantly improved, and the drug-loaded gelatin nanogel, the biomimetic nanogel and a chemotherapeutic drug are combined to treat pancreatic cancer, have a significant anti-tumor effect, and the combined treatment of the biomimetic nanogel and gemcitabine has a synergistic anti-tumor effect.The gelatin realizes effective regulation of the dense fibrosis microenvironment of pancreatic cancer, and provides a new feasible strategy for the treatment of pancreatic cancer.

A retinoic acid prodrug to which a boron functional group having a structure represented by chemical formula 1 is bound is described. The retinoic acid prodrug self-assembles to form nanoparticles. Therefore, an anticancer drug composition comprises the same as an active ingredient. According to the retinoic acid prodrug, targeted therapy of tumor cells is possible through the synergistic anticancer effect of retinoic acid and the boron functional group and the surface modification of particles. In particular, the retinoic acid prodrug enables a drug loading of 100 wt %, and thus can provide an effective anticancer drug.

The invention relates to the technical field of molecular oncology and drug resistance mechanism research, and discloses an S232F site of acquired drug resistance of a fusion gene STRN3-RARA and application of the S232F site in ATRA. The product is used for detecting the sensitivity of a patient suffering from acute promyelocytic leukemia to all-transretinoic acid (ATRA) treatment or screening whether the patient suffering from acute promyelocytic leukemia is resistant to ATRA treatment, an S232F mutation site is an STRN3-RARA fusion gene coding protein region mutation site, and the nucleotide sequence of the STRN3-RARA fusion gene is shown as SEQ ID NO: 1. The S232F mutation site is located at the 974th nucleotide site of the nucleotide sequence, and the base C is mutated into T. According to the present invention, the S232F mutation site can be adopted as the drug resistance detection marker, the reagent or the kit can be designed according to the STRN3-RARA gene S232F mutation site so as to be used for clinical drug resistance detection, and the gene mutation state of the patient can be monitored so as to guide the personalized drug use.

The invention discloses a surface-engineered iron-nitrogen-selenium monatomic nano-enzyme loaded with all-trans retinoic acid, which comprises an inner core and all-trans retinoic acid loaded on the surface of the inner core, and the inner core is a selenium-rich organic nano-enzyme inner core. The invention also discloses a corresponding preparation method and application thereof. The ATRA is loaded on the surface of the inner core, the inner core can regulate the active oxygen level in target cells so as to cooperate with all-transretinoic acid to induce acute myelogenous leukemia cell differentiation, the regulating effect of the nano-enzyme on ROS and the differentiation promoting effect of the ATRA generate a synergistic effect, the differentiation induction effect on AML cells is remarkably enhanced, and the differentiation induction effect on the AML cells is remarkably improved. The problem of drug resistance of ATRA single-drug treatment is solved. The nano-enzyme disclosed by the invention not only can effectively inhibit proliferation and infiltration of leukemia cells, but also can promote repair of a bone marrow hematopoietic microenvironment and recovery of a hematopoietic function, and provides a targeted redox differentiation enhancement treatment strategy with clinical transformation potential for acute myelogenous leukemia.

The invention discloses application of ziyuglycoside II in preparation of a medicine for treating and relieving acute promyelocytic leukemia and / or ATRA-resistant acute promyelocytic leukemia and a medicine composition, and belongs to the technical field of medicine. Experiments prove that ziyuglycoside II can inhibit proliferation of acute promyelocytic leukemia cells (NB4) and transretinoic acid (ATRA) drug-resistant acute promyelocytic leukemia cells (NB4-R2), induce differentiation of the NB4 and the NB4-R2, promote apoptosis of the NB4-R2 cells and relieve disease development of ATRA drug-resistant cell xenotransplantation acute promyelocytic leukemia. The ziyuglycoside II is developed as a novel drug for resisting acute promyelocytic leukemia or an auxiliary component thereof, and the ziyuglycoside II has obvious effects of resisting acute promyelocytic leukemia and drug-resistant acute promyelocytic leukemia; the invention provides a new approach and means for treating acute promyelocytic leukemia and drug-resistant acute promyelocytic leukemia.