Recently,a large number of antibodies have been utilized as biodrugs,and their subcutaneous formulations are required to allow the self-administration.However,because of the lower administration capacity of subcutaneo...Recently,a large number of antibodies have been utilized as biodrugs,and their subcutaneous formulations are required to allow the self-administration.However,because of the lower administration capacity of subcutaneous formulation than intravenous ones,highly-concentrated antibody formulations(>100 mg/mL)are desired.Regretfully,highly-concentrated antibodies often cause aggregation during the long-term storage and transportation,resulting in the loss of pharmacological activity and induction of immunogenicity.On the other hand,we previously reported the potential use of polypseudorotaxane(PPRX)hydrogels consisting of polyethylene glycol(PEG,MW 20,000)and cyclodextrins(CyDs)as sustained release systems for protein drugs such as insulin and lysozyme.展开更多
Fulminant hepatitis is a serious, life-threatening disorder and is associated with inflammatory cytokines produced by Kupffer cells. However, a number of clinical trials for the treatment of fulminant hepatitis did no...Fulminant hepatitis is a serious, life-threatening disorder and is associated with inflammatory cytokines produced by Kupffer cells. However, a number of clinical trials for the treatment of fulminant hepatitis did not show enough substantial benefits. Since NF-κB is a key mediator of inflammatory response in Kupffer cells, NF-κB decoy would be an attractive candi-datefor the treatment of fulminant hepatitis.展开更多
In the clinical field,insulin has been used for treatment of diabetes.However,insulin often shows low physicochemical stability,adsorption onto tubes and enzymatic degradation in injection site or blood.Previously,we ...In the clinical field,insulin has been used for treatment of diabetes.However,insulin often shows low physicochemical stability,adsorption onto tubes and enzymatic degradation in injection site or blood.Previously,we demonstrated that cyclodextrins(CyDs),especially branchedβ-CyDs,improve the pharmaceutical properties of insulin through complexation with its aromatic residues.However,little has been reported on the insulin conjugate with branchedβ-CyD.In the present study,to improve the pharmaceutical properties of insulin,we newly prepared 6-Ο-α-(4-Ο-α-D-glucuronyl)-D-glucosyl-β-CyD(GUG-β-CyD)conjugate with insulin,and evaluated its thermal or enzymatic stability and adsorption onto glass or polypropylene tube[1].展开更多
GM1-gangliosidosis is a rare lysosomal storage disorder characterized clinically by a wide range of variable neurovisceral,ophthalmological and dysmorphic features. Without enough functionalβ-galactosidase, GM1-gangl...GM1-gangliosidosis is a rare lysosomal storage disorder characterized clinically by a wide range of variable neurovisceral,ophthalmological and dysmorphic features. Without enough functionalβ-galactosidase, GM1-gangliosides cannot be degraded in lysosomes, and accumulate to toxic levels in many tissues and organs, particularly in the brain. In spite of several approaches for the treatment of GM1-gangliosidosis.展开更多
Atopic dermatitis is a skin disease characterized by inflammation, pruritus, and chronic or relapsing eczematous lesions. Recently, ampholytic polysaccharide sacran has attracted a particular focus of attention as a n...Atopic dermatitis is a skin disease characterized by inflammation, pruritus, and chronic or relapsing eczematous lesions. Recently, ampholytic polysaccharide sacran has attracted a particular focus of attention as a novel biomaterial. In the present study, we investigated the effect of sacran solution on atopic dermatitis in the clinical study. Almost all of the average scores for atopic dermatitis symptoms of each patient treated with sacran solutions were improved. In addition, the scores of sleep disorder and itching were also significantly ameliorated by the sacran treatment for 4 weeks, compared with those of initial states. In immatured dermal skin model stimulated with 2,4-dinitrofluorobenzene (DNFB), the sacran treatment markedly down-regulated inflammatory cytokine and chemokine mRNA levels such as MCP-1, TNF-α, IL-1β, and IL-6 mRNAs, compared with that of DNFB alone. Furthermore, a sacran solution significantly suppressed the mRNA expression of TNF-α and COX-2 in RAW264.7 cells, a murine macrophage-like cell line, stimulated with phorbol-12-myristate-13-acetate (PMA). In RBL-2H3 cells, a rat basophilic leukemia cell line, a sacran solution significantly lowered β-hexosaminidase release, indicating the suppression of allergic response. These results suggest that a sacran solution may have the potential to improve atopic dermatitis through the impairment of production of inflammatory cytokine and chemokine mRNA.展开更多
文摘Recently,a large number of antibodies have been utilized as biodrugs,and their subcutaneous formulations are required to allow the self-administration.However,because of the lower administration capacity of subcutaneous formulation than intravenous ones,highly-concentrated antibody formulations(>100 mg/mL)are desired.Regretfully,highly-concentrated antibodies often cause aggregation during the long-term storage and transportation,resulting in the loss of pharmacological activity and induction of immunogenicity.On the other hand,we previously reported the potential use of polypseudorotaxane(PPRX)hydrogels consisting of polyethylene glycol(PEG,MW 20,000)and cyclodextrins(CyDs)as sustained release systems for protein drugs such as insulin and lysozyme.
文摘Fulminant hepatitis is a serious, life-threatening disorder and is associated with inflammatory cytokines produced by Kupffer cells. However, a number of clinical trials for the treatment of fulminant hepatitis did not show enough substantial benefits. Since NF-κB is a key mediator of inflammatory response in Kupffer cells, NF-κB decoy would be an attractive candi-datefor the treatment of fulminant hepatitis.
文摘In the clinical field,insulin has been used for treatment of diabetes.However,insulin often shows low physicochemical stability,adsorption onto tubes and enzymatic degradation in injection site or blood.Previously,we demonstrated that cyclodextrins(CyDs),especially branchedβ-CyDs,improve the pharmaceutical properties of insulin through complexation with its aromatic residues.However,little has been reported on the insulin conjugate with branchedβ-CyD.In the present study,to improve the pharmaceutical properties of insulin,we newly prepared 6-Ο-α-(4-Ο-α-D-glucuronyl)-D-glucosyl-β-CyD(GUG-β-CyD)conjugate with insulin,and evaluated its thermal or enzymatic stability and adsorption onto glass or polypropylene tube[1].
文摘GM1-gangliosidosis is a rare lysosomal storage disorder characterized clinically by a wide range of variable neurovisceral,ophthalmological and dysmorphic features. Without enough functionalβ-galactosidase, GM1-gangliosides cannot be degraded in lysosomes, and accumulate to toxic levels in many tissues and organs, particularly in the brain. In spite of several approaches for the treatment of GM1-gangliosidosis.
文摘Atopic dermatitis is a skin disease characterized by inflammation, pruritus, and chronic or relapsing eczematous lesions. Recently, ampholytic polysaccharide sacran has attracted a particular focus of attention as a novel biomaterial. In the present study, we investigated the effect of sacran solution on atopic dermatitis in the clinical study. Almost all of the average scores for atopic dermatitis symptoms of each patient treated with sacran solutions were improved. In addition, the scores of sleep disorder and itching were also significantly ameliorated by the sacran treatment for 4 weeks, compared with those of initial states. In immatured dermal skin model stimulated with 2,4-dinitrofluorobenzene (DNFB), the sacran treatment markedly down-regulated inflammatory cytokine and chemokine mRNA levels such as MCP-1, TNF-α, IL-1β, and IL-6 mRNAs, compared with that of DNFB alone. Furthermore, a sacran solution significantly suppressed the mRNA expression of TNF-α and COX-2 in RAW264.7 cells, a murine macrophage-like cell line, stimulated with phorbol-12-myristate-13-acetate (PMA). In RBL-2H3 cells, a rat basophilic leukemia cell line, a sacran solution significantly lowered β-hexosaminidase release, indicating the suppression of allergic response. These results suggest that a sacran solution may have the potential to improve atopic dermatitis through the impairment of production of inflammatory cytokine and chemokine mRNA.
