49 results about "Acid sphingomyelinase" patented technology

The invention relates to dose escalation enzyme replacement therapy using acid sphingomyelinase (ASM) for the treatment of human subjects having acid sphingomyelinase deficiency (ASMD), and, in particular, patients with non-neurological manifestations of Niemann-Pick Disease (NPD), and in certain embodiments, NPD type B.

The present invention provides a method for treating individuals affected with the acid sphingomyelinase-deficient forms of Niemann-Pick disease (i.e., Type A or Type B Niemann-Pick) by administering small molecules as specific molecular “chaperones” for the deficient acid sphingomyelinase (ASM) enzyme associated with the disease. The molecules are ceramide, sphingomyelin, or phosphonucleotide analogues.

This disclosure pertains to methods and compositions for tolerizing a mammal's brain to exogenously administered acid sphingomyelinase polypeptide by first delivering an effective amount of a transgene encoding the polypeptide to the mammal's hepatic tissue and then administering an effective amount of the transgene to the mammal's central nervous system (CNS).

Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

Deficiencies in the enzymatic activity of acid sphingomyelinase (ASM) result in Niemann-Pick disease. A variety of modifications which eliminate the activity of the free thiol on the C-terminal cysteine residue of ASM all result in substantially increased specific activity of the enzyme. Methods used to alter the activity of this residue include site-directed mutagenesis to delete or alter the residue, enzymatic degradation of the ASM to remove the residue, copper-promoted dimerization of ASM (via the terminal cysteine residues) and chemical modification of the free thiol group on this residue.

The invention belongs to the fields of innovative medicines and cosmetics and particularly relates to a preparing method and uses of mangostin shown as a formula (I) and mangostin analogues shown as a formula (II). Alpha-mangostin, beta-mangostin, gamma-mangostin and analogues thereof are respectively prepared through olefination and through controlling conditions for deprotection. According to the method, products are high in purity, operation is simple and convenient, yields are high, costs are low and the method is suitable for large-scale production. On one hand, the beta-mangostin, the gamma-mangostin, beta-methoxy-mangostin, and analogues thereof have ultraviolet absorption ability and ultraviolet light radiation preventing functions so that the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof can be adopted as a sun-screening agent separately or compounded with other sun-screening agents and applied into cosmetics; and on the other hand, the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof have activity of inhibiting acid sphingomyelinase so that the beta-mangostin, the gamma-mangostin, the beta-methoxy-mangostin, and the analogues thereof can be adopted as acid sphingomyelinase inhibitors and applied for preparation of medicines for preventing and treating acid sphingomyelinase related diseases mainly including cardio cerebrovascular diseases, neurological diseases, liver diseases, lung diseases, autoimmune diseases, infectious diseases and the like.

The invention belongs to the field of innovative drugs and cosmetics, and particularly relates to a 1,3,6,7-tetrahydroxy xanthone derivative shown in the formula (I) and the formula (II) and a preparing method and application of the derivative to medicine and cosmetics. The derivative is prepared through an olefination reaction. An ultraviolet spectrophotometer is adopted to measure the ultraviolet absorption spectrum of the compound in the 280-400 nm ultraviolet interval, and the result shows that the 1,3,6,7-tetrahydroxy xanthone derivative has ultraviolet absorption capacity and the ultraviolet radiation resisting function and can be applied to cosmetics serving as a sun-screening agent or being compounded with other sun-screening agents. The result of in-vitro acid sphingomyelinase inhibitory activity tests shows that the compound has acid sphingomyelinase inhibitory activity and can be applied to preparation of drugs for preventing and treating diseases related to acid sphingomyelinase serving as an acid sphingomyelinase inhibitor, wherein cardiovascular and cerebrovascular diseases, nervous system diseases, hepatic diseases, lung diseases, autoimmune diseases, infectious diseases, cancers and the like are mainly involved.

The invention provides a moisturizing mask and a preparation method thereof. The moisturizing mask comprises the following components, by weight: 0.01 to 1% of saccharide isomeride, 0.01%-1% of rhizobium gum, 0.01%-1% of tremella extract, 0.01%-0.2% of sodium hyaluronate, 0.01%-1% of codium tomentosum extract, 0.04%-1.5% of a skin conditioner, 0.1%-0.3% of a pH regulator, 0.06%-0.45% of a thickener and the balance being water. According to the moisturizing mask, various moisturizing active matters are mixed based on a scientific proportion; gene expression of filaggrin, loricrin, hyaluronan synthase-3 and acid sphingomyelinase in the skin can be up-regulated and the water locking capacity of the skin can be improved; meanwhile, synthesis of ceramide and cerebroside is promoted, absorptionof the skin to surrounding moisture is improved, so that the purpose of efficient moisturizing is achieved.

The present invention relates to the acid sphingomyelinase gene and to methods of diagnosing Niemann-Pick disease. It is based, at least in part, on the cloning and expression of the full-length cDNA encoding acid sphingomyelinase and on the discovery of mutations in the acid sphingomyelinase gene of Ashkenazi Jewish Niemann-Pick disease patients.

Deficiencies in the enzymatic activity of acid sphingomyelinase (ASM) result in Niemann-Pick disease. A variety of modifications which eliminate the activity of the free thiol on the C-terminal cysteine residue of ASM all result in substantially increased specific activity of the enzyme. Methods used to alter the activity of this residue include site-directed mutagenesis to delete or alter the residue, enzymatic degradation of the ASM to remove the residue, copper-promoted dimerization of ASM (via the terminal cysteine residues) and chemical modification of the free thiol group on this residue.

The invention belongs to the field of medicinal chemistry and in particular relates to a hydroxamic acid-containing substituted heterocyclic compound as well as a preparation method and application thereof. The specific structure of the compounds provided by the invention is shown as a formula I, and the compounds have acid sphingomyelinase inhibitory activity. The invention further provides a synthetic method of compounds in the formula I and application of the compounds in atherosclerosis and depression. The compounds can be used for developing related drugs for treating atherosclerosis (AS), diabetes, pulmonary emphysema, pulmonary edema, pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, pulmonary arterial hypertension, non-alcoholic fatty liver disease, Alzheimer's disease (AD), multiple sclerosis (MS), cerebral apoplexy and depression. The structural formula is as shown in the specification.

Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

The present invention provides a method for treating individuals affected with the acid sphingomyelinase-deficient forms of Niemann-Pick disease (i.e., Type A or Type B Niemann-Pick) by administering small molecules as specific molecular “chaperones” for the deficient acid sphingomyelinase (ASM) enzyme associated with the disease. The molecules are ceramide, sphingomyelin, or phosphonucleotide analogues.

The invention discloses a compound with phosphodiesterase 4D and acid sphingomyelinase inhibitory activity. The compound has good PDE4D / ASM double-target inhibitory activity and can be used for preventing and / or treating diseases associated with the phosphodiesterase 4D and the acid sphingomyelinase, and the diseases particularly include inflammatory diseases, autoimmune diseases such as dermatitis, atopic dermatitis, psoriasis and multiple sclerosis, cardiovascular diseases such as atherosclerosis and ischemia reperfusion injury, hepatic diseases such as non-alcoholic steatohepatitis, alcoholic steatohepatitis and hepatic fibrosis, mental and neurological diseases such as depression and anxiety disorder, neurodegenerative diseases such as Alzheimer's diseases, respiratory system diseasessuch as chronic obstructive pulmonary diseases, cystic fibrosis, pulmonary fibrosis, pulmonary edema and lung injury and metabolic diseases such as diabetes.

Belonging to the field of medicinal chemistry, the invention in particular relates to acid sphingomyelinase. The acid sphingomyelinase inhibitor provided by the invention has a specific structure shown as formula I. The invention also provides a synthesis method of the compound shown as formula I and application of the compound in apoptosis and inflammation related diseases including atherosclerosis (AS), diabetes, emphysema, pulmonary edema, pulmonary fibrosis, cystic fibrosis, nonalcoholic fatty liver, Alzheimer's disease (AD), multiple sclerosis (AD), cerebral stroke and depression.

The invention discloses a specific codominant acid sphingomyelinase (ASM) marker at a site of a Chinese cabbage, and the specific codominant ASM marker at the site of the Chinese cabbage is directly related to identification of a wild type and a base deletion mutant at the eIF(iso) 4E.c of the Chinese cabbage. A marker related to detection of the site of the wild type is named as ASM-W, the size of a segment is 128bp, as shown in SEQ ID No.1. A marker related to detection of the corresponding site of the base deletion mutant is named as ASM-m, and the size of a segment is 124bp, as shown in SEQ ID No.2. According to a specific molecular marker of the deletion mutation of a base at the site of eIF(iso) 4E.c of the Chinese cabbage and application of the specific molecular marker, the homologous cloning technology is utilized to find a mutant at the side of eIF(iso) 4E.c, and the specific molecular marker used for indentifying the site is developed. The specific molecular marker can be utilized for accurate selection of genotypes of backcrossing descendants. At the same time, the specific molecular marker can also be used for sorting out Chinese cabbage germplasm resources to seek for mutant materials which are more abundant in genetic background.

Based on the observation that the application of small amounts of exogenous acid sphingomyelinase to generate endogenous ceramide, or provision of exogenous long-chain natural C16-ceramide resulted in rapid translocation of vacuolar daunorubicin into the nucleus in multi-drug resistant (MDR) cells, the present invention relates to a nano-liposomal preparation that includes C16-ceramide. Exposure of MDR cells to the C16:0 ceramide-based nanoliposomes provide a mechanism to reverse MDR in chemoresistant cells and tumors, by inducing rapid translocation of chemotherapeutic agent from cytoplasmic vesicles to the nucleus.

Alzheimer's disease (AD) is the most common human neurodegenerative disease of the CNS resulting in progressive neuronal death and memory loss. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. It was discovered that antisense oligonucleotide against neutral sphingomyelinase and GW4869, a chemical inhibitor of neutral sphingomyelinase, inhibit activation of glial cells and protect neurons in AD cell culture and animal models. These results suggest the following new treatment options for AD patients: Antisense oligonucleotide against neutral sphingomyelinase and GW4869.

A method of treating retinal diseases is disclosed that includes the step of administering an effective amount of a composition including an ASMase inhibitor to a retinal disease patient, wherein at least one disease symptom is either lessened or progression of the symptom is delayed.

The present invention relates to a method for treating degenerative neurological disorders in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising an acid sphingomyelinase (ASM) activity inhibitor or expression inhibitor as an active ingredient.

The present invention relates to a chemically defined medium for eukaryotic cell culture, comprising water, at least one carbon source, one or more vitamins, one or more salts, one or more fatty acids, one or more buffer components, selenium, at least one substance of the group of functional inhibitors of acid sphingomyelinase (FIASMAs) and at least one polypeptide of the TGF-beta superfamily withthe ability to inhibit stem cell differentiation, its use in the culture of human pluripotent stem cells, a cell culture system comprising human pluripotent stem cells and the chemically defined medium, as well as a kit for proliferation and / or maintenance of human pluripotent stem cells.

Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

The invention belongs to the field of medicinal chemistry, and specifically relates to a substituted heterocyclic compound containing hydroxamic acid, a preparation method and application thereof. The specific structure of the compound provided by the present invention is shown in formula I, and has acid sphingomyelinase inhibitory activity. The present invention also provides a synthesis method of the compound in formula I and its effect on atherosclerosis and depression. This kind of compound can be used to develop and treat atherosclerosis (AS), diabetes, emphysema, pulmonary edema, pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, pulmonary arterial hypertension, non-alcoholic fatty liver, Alzheimer's Drugs related to AD, multiple sclerosis (MS), stroke, and depression.

The present invention provides novel antisense ribozymes useful for inhibiting the activity of neutral sphingomyelinase. Also provided are methods for reducing the activity of neutral sphingomyelinase, as well as methods for reducing apoptosis and atherosclerosis using the ribozymes of the invention.

The invention discloses use of polygonum hydropiper aldehyde compounds as an acid sphingomyelinase inhibitor. Spikenard guaiacum ketone C, spikenard guaiacum ketone D, deacetylated anthraquinone cynaropicrin, parishin B, polygonic acid, polygonum hydropiper hemiacetal and 14-deacetylated farfaratin are found to have excellent inhibitory activity on acid sphingomyelinase, thus being developed intothe acid sphingomyelinase inhibitor for treating diseases caused by the rise of the acid sphingomyelinase.

The invention discloses an application of carbonic anhydrase 1 and acid sphingomyelinase-like phosphodiesterase 3a as molecular markers in colorectal cancer diagnosis. The application is characterized by screening the differential biomarkers in the colorectal cancer tissues and the far-end normal tissues and the differential biomarkers in the serum of colorectal cancer patients and the cancer-free control people through a high-throughput chromatography-mass spectrometry-based proteomics technology; screening the colorectal cancer related candidate biomarkers through the comparative analysis of the proteomics results of the tissue and serum samples; verifying the colorectal cancer distinguishing capability of the biomarker through an external database; and finally, detecting the colorectal cancer biomarker of the serum of a case control group by a low-flux method, and evaluating the diagnostic ability of the marker on the colorectal cancer. Based on the screened biomarkers, a rapid, sensitive and specific standard method system for colorectal cancer diagnosis is attempted to be established, and help is provided for the large-scale population screening and clinical diagnosis.

This disclosure pertains to methods and compositions for tolerizing a mammal's brain to exogenously administered acid sphingomyelinase polypeptide by first delivering an effective amount of a transgene encoding the polypeptide to the mammal's hepatic tissue and then administering an effective amount of the transgene to the mammal's central nervous system (CNS).