205 results about "Advanced Glycosylation End Products" patented technology

The present invention provides a composition comprising an effective amount of benfotiamine and an effective amount of pyridoxamine in a suitable vehicle for topical application. The present compositions are useful in improving the appearance of aged skin characterized by wrinkles, loss of elasticity, and hyperpigmentation caused by chronoaging and / or photoaging of skin, by inhibiting particularly skin damage resulting from reactive carbonyl species (RCS), glycation of skin proteins, formation of advanced glycation endproducts (AGEs) and formation of advanced lipoxidation endproducts (ALEs).

Antibodies that bind specifically to receptor for advanced glycation end products (RAGE) and RAGE-binding fragments thereof are disclosed. Also disclosed are pharmaceutical compositions comprising such anti-RAGE antibodies and RAGE-binding antibody fragments thereof, and their use for treatment of RAGE related diseases.

The present application relates to isolated proteins, particularly monoclonal antibodies, in particular CDR-grafted, humanized antibodies which bind to RAGE protein. Specifically, these antibodies have the ability to inhibit the binding of RAGE to its various ligands. The antibodies or portions thereof of described in the present application are useful for treating a disease or disorder characterized by or induced by pathophysiological ligands of RAGE, for example misfolded proteins like amyloid B and advanced glycation-end-products.

Fusion proteins comprising a Receptor for Advanced Glycation End Products Ligand Binding Element (RAGE-LBE) and an immunoglobulin element are disclosed. Also disclosed are fusion proteins comprising a RAGE-LBE and a dimerization domain. Also disclosed are nucleic acids encoding such fusion proteins and methods for using disclosed nucleic acids and proteins to, for example, treat RAGE-related disorders. Additional compositions and methods are also disclosed.

Novel peptides are useful as antagonists of RAGE and may be used to treat cancer, inflammation, diabetes and arthritis through the administration of a therapeutically effective amount of the peptide to a subject in need thereof.

The invention discloses an application of coumarin with a structure of formula IA or formula IB in preparing formation inhibitors of AGEs. Coumarin compounds can be used for treating and preventing various chronic diseases caused by the formation and the crosslinking of the AGEs, can also be used for preparing cosmetics with epidermis and papillary dermis anti-aging and remodeling activities and / or anti-wrinkle activities for inhibiting the formation and the crosslinking of the AGEs, and can further be used for preparing chemical agents for preventing denaturation of protein in food.

The object of this invention is to elucidate the factors involved in the regulation of AGE (advanced glycation endproducts, which are produced in a living body accompanied with diabetes and aging) and RAGE (the receptor for AGE), in order to facilitate investigation on the biological activities, physiological phenomenon and diseases related to AGE and RAGE. Plural molecular species are known to exist for RAGE, and among such molecular species, soluble RAGE exhibits the activity to modulate interaction between AGE and transmembrane-type RAGE. Using this soluble RAGE or a nucleic acid encoding it, the soluble RAGE can be measured, in addition, investigation on various physiological phenomenon, biological activities, and diseases related to interaction between AGE and RAGE can be performed to facilitate development a medicine having further efficacy.

The invention relates to methods for identifying compounds which affect cellular stress. In particular, the method relates to identifying compounds which inhibit protein advanced glycation end product formation, where the compounds are carbonyl scavengers which inhibit the formation. The assay involves combing the substance of interest with histone H1 and ADP-ribose, and then measuring fluorescence and protein cross linking. Various inhibitors ofprotein AGE glycation have been identified, using this assay.

Various methods of administering medication(s) that inhibit the nonenzymatic formation of glycation and dehydration condensation complexes known as advanced glycation end-products (AGEs) or modulate the advanced glycation end-product receptor (RAGE) are provided. Also, a medication releasing medical devices, wherein at least a portion of the medical device releasably includes at least one of these medication(s) are provided.

This invention is of particular use to patients with Diabetes Mellitus. It uses alkyl analogs of the methyl pyruvate (MP) family to provide energy and improve insulin and glucose homeostasis via accelerated intracellular delivery of protons and ATP from each MP. The energy upregulates cellular cross talk and networking resulting in a surge of ATP enabling NADH (via glycolysis) that enables pancreatic islet cells to obtain increased ATP allowing excess insulin manufacture. This process improves cellular respiration and expedites protein, lipid and hormone manufacture. The increased energy also enables telomeres and delays Hayflick limit. Instead of cellular repair, silence, or apoptosis, energy is allocated for cell / organ function. This invention curbs inflammation and ROS by idealizing cellular respiration and diminishing hyperglycemia. In turn a reduction of advanced glycation end products (AGEs), lessened target RNA and nucleic acid toxins, i.e., diminished HbA1c occurs. By decreased drain of cellular energy, genomic function improves.

The present application relates to isolated proteins, particularly monoclonal antibodies, in particular CDR-grafted, humanized antibodies which bind to RAGE protein. Specifically, these antibodies have the ability to inhibit the binding of RAGE to its various ligands. The antibodies or portions thereof of described in the present application are useful for treating a disease or disorder characterized by or induced by pathophysiological ligands of RAGE, for example misfolded proteins like amyloid β and advanced glycation-end-products.

Coronary artery calcification (CAC) occurs at an earlier age in diabetes and is a risk factor for coronary artery disease (CAD) in subjects with or without diabetes. One postulated mechanism for the increased CAC is the accelerated accumulation of advanced glycation end products (AGEs) in the vasculature. As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel maker of collagen AGEs levels. The present invention provides methods and apparatuses for detecting SIF that can be a useful marker of CAD risk and a therapeutic target.

The invention provides an immunological analytical method and devices for determination of the advanced glycosylation end products (AGEs), comprising a reagents for determining the AGEs, which comprises a displaying carrier suspension and the antigen or antibody immobilized on the surface of the said displaying carrier; and a test strip, comprising of: a base plate, and constitutive parts provided on the said base plate. After infusing the said reagent into the said test strip, the immunological reaction of the AGEs antigen or antibody can be determined based on the agglutination phenomenon or accompanied changes of absorbance or color and the presence or raised level of the AGEs in the diabetic patient can be known accordingly such that the practitioner can prevent the occurrence of the complications, or block further the progression of the complications at the earlier stage.

The invention discloses a new clause of a five membered heterocylic ring compounds of general formula I and its pharmaceutically or cosmetically acceptable salts, wherein R1, R2, R3, R4, R5, A, B, X and Y are as defined in the specification. The invention also discloses a process for preparation of these compound and their therapeutic and cosmetic applications particularly in the management of aging related and diabetic vascular complications. The compounds in question act by triple action of an AGE (Advanced Glycation Endproducts) breaker, AGE inhibitor and free radical scavenger which make them most suitable in different therapeutic and cosmetic applications. The invention also discloses pharmaceuticals and cosmetic compositions comprising these compounds and method of treatment of diseases caused by accumulation of AGE and / or free radicals in the body cells.

This invention provides for a method for inhibiting new tissue growth in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit new tissue growth in the subject's blood vessels. The invention also provides for method for inhibiting neointimal formation in blood vessels in a subject, wherein the subject experienced blood vessel injury, which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to inhibit neointimal formation in the subject's blood vessels. The invention also provides a method for preventing exaggerated restenosis in a diabetic subject which comprises administering to the subject a pharmaceutically effective amount of an inhibitor of receptor for advanced glycation endproduct (RAGE) so as to prevent exaggerated restenosis in the subject.

Control of blood glucose is a fundamental goal in the treatment of diabetes mellitus. Glycation of l-lysine can lower blood glucose and advanced glycation end product (AGE) free adducts can be excreted in the urine. Lysine, an inexpensive amino acid, can be administered orally or parentally, and can be incorporated into a stereocomplex matrix as a time released preparation. In patients who suffer from diabetes and concomitant renal insufficiency who cannot clear sufficient quantities of AGE free adducts enantiomeric mixtures of lysine will lower blood glucose and AGEs since d-lysine has been shown to decrease protein glycation and lower hemoglobin Alc. This invention is not intended to replace insulin or oral hypoglycemic agents but is does offer patients a low cost and probably safe complementary therapy for the treatment of diabetes mellitus. In addition to the treatment of diabetes and its complications, this invention could lower AGE burden and slow or ameliorate some of the consequences of aging.

The present invention provides novel therapeutics and methods of treatment for diseases associated with activation of the advanced glycation endproducts receptor (RAGE).

The object of this invention is to elucidate the factors involved in the regulation of AGE (advanced glycation endproducts, which are produced in a living body accompanied with diabetes and aging) and RAGE (the receptor for AGE), in order to facilitate investigation on the biological activities, physiological phenomenon and diseases related to AGE and RAGE. Plural molecular species are known to exist for RAGE, and among such molecular species, soluble RAGE exhibits the activity to modulate interaction between AGE and transmembrane-type RAGE. Using this soluble RAGE or a nucleic acid encoding it, the soluble RAGE can be measured, in addition, investigation on various physiological phenomenon, biological activities, and diseases related to interaction between AGE and RAGE can be performed to facilitate development a medicine having further efficacy.

The invention relates to a sealwort extract as well as a preparation method and a use thereof. The sealwort extract is prepared by use of a method comprising the steps of performing reduced-pressure reflux on an extract obtained by performing ethanol hot extraction on sealwort, thereby obtaining a total extract, adding distilled water to the total extract for suspending, extracting by use of isovolumetric petroleum ether, ethyl acetate and n-butyl alcohol orderly, and recovering the solvents under reduced pressure, thereby obtaining an ethyl acetate extract part; the sealwort extract has inhibition effect on AGEs (Advanced Glycation End Products), and thus can be further applied to preparing medicines for treating diabetes and complications thereof and has important clinical application value.

The present invention provides for a method to prevent accelerated atherosclerosis in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent accelerated atherosclerosis in the subject. The present invention also provides for a method to prevent a macrovessel disease in a subject predisposed thereto which comprises administering to the subject a polypeptide derived from soluble receptor for advanced glycation endproduct in an amount effective to prevent macrovessel disease in the subject.

The present invention discloses a use of lotus procyanidin as an advanced glycosylation end product formation inhibitor. The drug composition adopting the lotus procyanidin as a main active component comprises the following nature active component extracts, by weight, 70-80% of lotus procyanidin, 10-20% of a synergist such as VE, VC, epigallocatechin gallate (EGCG), cysteine and other ??complexes, and 5-10% of other nature extracts such as a lotus leaf extract, a ginkgo leaf extract and the like. According to the present invention, a high performance liquid chromatography method is adopted to detect a methylglyoxal removing effect of the lotus procyanidin and the main structure unit thereof (catechin), wherein methylglyoxal is an important intermediate substance during an advanced glycosylation end product formation process; a high performance liquid chromatography / multi-stage mass spectrometry method is adopted to identify adducts of four catechin and methylglyoxal and adducts of nine lotus procyanidin and methylglyoxal; and results show that lotus procyanidin provides good inhibition effects for advanced glycosylation end product formation in simulated physiological environments and simulated food systems.

The invention discloses a method for detecting advanced glycation end products (AGEs) in main stream smoke of a cigarette. The method specifically comprises analysis and determination of carboxy methyl lysine (CML) and carboxyethyl lysine (CEL). The method comprises the following steps: trapping total particulate matter of cigarette smoke by virtue of a Cambridge filter; carrying out ultrasonic extraction on the filter with a hydrochloric acid solution; and carrying out analysis by combining a cation exchange solid-phase extraction column purification method with liquid chromatogram-tandem mass spectrometry (LC-MS / MS). The method has the characteristics that (1) a detection method for AGEs in the main stream smoke of the cigarette is built for the first time; (2) a sample pretreatment method is built according to the characteristics of cigarette smoke sample matrix, derivative reaction is not required, and the pretreatment is simple and efficient; and (3) the method is high in sensitivity, good in qualitative accuracy and suitable for analysis of large batches of samples.

The present invention relates to advanced glycation end product (AGE) inhibitors or health functional foods for inhibiting an occurrence of diabetic complications, comprising a compound isolated from Morus Bark as active ingredients. Particularly, the present invention comprises a compound selected from the group consisting of mulberrofuran G, mulberrofuran K, kuwanon G, kuwanon Z, oxyresveratrol, 2',4',5,7-tetrahydroxyflavanone, morusignin L and dihydromorin isolated from Morus Bark. The compounds disclosed above inhibit the production of AGE which is a causative substance of diabetic complications. Thus, the compounds could be used as an AGE inhibitor and a health functional food for inhibiting diabetic nephropathy, diabetic retinopathy and diabetic neuropathy.

Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins). Also disclosed are therapeutic methods of using such inhibitors to treat glycogen storage diseases, including Fanconi's syndrome, as well as other pathological conditions resulting from the formation of AGE-proteins.

The invention discloses a detection method of a peptide-advanced glycation end product. The detection method is characterized by comprising the following steps: (1) removing a dicarbonyl compound in a liquid sample; (2) removing impurities and gathering the peptide-advanced glycation end product in the sample by using a solid-phase extraction technique; (3) determining the nature of the gathered peptide-advanced glycation end product; (4) carrying out enzymolysis on the gathered peptide-advanced glycation end product by using peptidase, removing the peptidase by using a filter membrane to obtain free peptide-advanced glycation end product; (5) quantitatively analyzing the free peptide-advanced glycation end product through mass spectrometric analysis. The method is capable of detecting the peptide-advanced glycation end product at a high flux and lowering the complexity of the quantitative detection of the peptide-advanced glycation end product; meanwhile, according to the method, the detection limit is relatively good, the linear relation between a concentration of a target product and a peak area of a signal is good, and the quantitative effect is good.

A method and medicament is provided for treating and inhibiting interaction of the receptor for advanced glycation end-products (RAGE) and its ligands using a natural or synthetic sulfated polysaccharide, preferably a 2-O desulfated heparin. The medicament preferably is administered intravenously, by aerosolization, intra-nasally, intra-articularly, intra-thecally, subcutaneously, topically or orally. The medicament is useful for treating a variety of conditions, including diabetes, inflammation, renal failure, aging, systemic amyloidosis, Alzheimer's disease, inflammatory arthritis, atherosclerosis, and colitis.

The invention relates to a liquid-phase chip kit for acute coronary syndrome and a preparation method for the same. A liquid-phase chip mainly comprises microspheres coated with oxidized low density lipoprotein (ox-LDL), soluble CD40 ligand (sCD40L), matrix metallopeptidase 9 (MMP-9), tissue factor (TF), omentin and endogenous secretory receptor of advanced glycation end products (esRAGE) capture antibody respectively, detection antibodies labelled by biotin, and streptavidin phycoerythrin. The liquid-phase chip provided by the invention has the advantages of being high in detection efficiency, low in the quantity of the needed samples, strong in specificity, high in sensitivity, rapid and accurate in detection, and the like. Simultaneously, the chip reflects a protective factor level and an injury factor level in an organism, so that the risk stratification and prognosis conditions of a patient can be much comprehensively assessed. Simultaneously, the preparation method disclosed by the invention is simple and practicable, and good in stability, various process parameters such as the quantities of the microspheres and the antibodies, and the reaction process in the technical scheme of the preparation method are obtained on the basis of lots of experiments, and are the optimal parameter values of the preparation process.

A composition comprising cartilage extract, grape seed extract and tomato extract was found to have remarkable anti-oxidant effect and free-radical inhibition. The tomato extract comprises lycopene. The composition which comprises a hydrophilic antioxidant, a lipophilic (hydrophobic) antioxidant, and a cartilage extract dramatically increases collagen synthesis in the dermis. Furthermore, the composition lowers collagenase activity and levels of advanced glycation end products (AGE). The signs of ageing, such as photoageing due to exposure to UV radiation, are related to the levels of collagen syntheses and free-radical oxidation. Compositions of the invention are intended for the treatment of ageing skin and the delaying of the onset of the signs of ageing in healthy skin.

The invention discloses a class-I carboxymethyl lysine removing agent and application thereof. The removing agent is a quinones substance formed by the oxidization of polyphenol containing a catechol or pyrogallol structure unit. The removing agent is applied to the reduction of the content of carboxymethyl lysine in a food system. The quinones substance has stronger capability of removing AGEs (Advanced Glycation End Products) in the food system of which the pH is neutral or alkaline, and when the quinones substance is added after the food system generates the CML or before the CML is generated, the level of the CML in the system can be effectively reduced.