32 results about "Complement inhibition" patented technology

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

The invention discloses acylated flavonoid glycoside compounds shown as a formula I and application thereof in preparation of complement inhibitor medicines. Acylated flavonoid glycosides extracted and separated from cudweed herb are proved to inhibit hemolysis caused by activation of a complement system in a classical pathway through in vitro experiments, and have complement inhibition effect; the activity of each monomericcompound is higher than that of a total extract of cudweed herb; and the acylated flavonoid glycoside compounds are good complement inhibitors and have low effective concentration, can serve as active ingredients to prepare novel complement inhibitor medicines for treating various diseases caused by abnormal activation of complements, are low in toxicity, safe in administration and rich in raw material sources and have great clinical application value. The structure of the formula I is shown as the specifications, wherein R1 and R2 are same or different, and respectively H, OH or OCH3; and R3 and R4 are respectively H or groups shown in the specifications.

The invention belongs to the field of Chinese medicine, relates to Prunella vulgaris polysaccharide, and a preparation method and purpose thereof in preparing anticomplement medicines. The Prunella vulgaris polysaccharide including uniform polysaccharide PW-PS1 and PW-PS2 is prepared from a dry fruit aqueous extract of a labiatae plant Prunella vulgaris Linn. Through in vitro tests, the uniform polysaccharide is proved to have strong anticomplement activity and inhibition effects on classical pathway and alternative pathway of a complement system; besides, the polysaccharide does not have the anticoagulant effect influencing in vivo activity and can be used for the preparation of complement inhibition medicaments. The PW-PS1 effects on C1q, C3 and C9 components of the complement system, and the PW-PS2 effects on the C1q, C2, C3, C5 and C9 components of the complement system.

The invention discloses a target fusion protein with the anti-inflammatory action, in particular an anti-P lectin single chain antibody target complement inhibitor ScFv-Crry and application thereof. The invention aims to provide the anti-P lectin single chain antibody target complement inhibitor ScFv-Crry with the specific targeting property and application of the ScFv-Crry to the preparation of medicines for treating organism inflammatory reactions. The anti-P lectin single chain antibody target complement inhibitor ScFv-Crry is the fusion protein which is obtained through the connection between an amino end connected with an anti-P lectin single chain antibody ScFv and a complement inhibitor Crry(1-319aa). Experiments show that the ScFv-Crry can remarkably improve the efficiency of the cell cracking mediated by an inhibiting complement, be highly aggregated at an immunity damaged position, and obviously inhibit the generation and development of inflammation. Therefore, the ScFv-Crry can be prepared into target P lectin complement inhibitor new genetic engineering target protein medicines aiming at treating inflammatory reactions. The ScFv-Crry has important contributions to the field of pharmacy and bright application prospect.

The invention discloses a complement inhibitor DAF mutant, a fusion protein thereof with a complement receptor 2 mutant and use of the fusion protein in preparation of medicines treating autoimmune diseases. The DAF mutant is a molecular modification obtained by computer modeling and amino acid substitution. The fusion protein of the DAF mutant and the complement receptor 2 mutant has higher ligand binding and dissociation rates than wild-sequence fusion protein thereof, and has better ligand binding force. Biological distribution experiments prove that the fusion protein can rapidly aggregatein the arthritis position after entering a rheumatoid arthritis mouse model, and has a significant anti-adhesion/anti-inflammatory targeted inhibitory effect. In treatment for MRL/lpr lupus erythematosus mice, the fusion protein can significantly increase the survival rate of the mice, and symptoms such as proteinuria, glomerular score, interstitial inflammation, vasculitis and crescent/necrosisin the mice in the treatment group are significantly improved.

The invention discloses a complement receptor 2 variant, a fusion protein of the complement receptor 2 variant and a complement inhibitor and application of the fusion protein in preparing a medicament for treating autoimmune diseases. The complement receptor 2 variant is a molecular modified body obtained after computer modeling and amino acid replacement, has higher ligand binding and dissociation rate and better ligand binding force than a wild sequence of the complement receptor 2 variant. The biological distribution experiment proves that the fusion protein provided by the invention can rapidly and highly aggregate at an arthritis part after entering a rheumatoid arthritis mouse model, and has a remarkable anti-adhesion/anti-inflammation targeted inhibition effect. In the treatment ofMRL/lpr lupus erythematosus mice, the fusion protein can obviously improve the survival rate of the mice, and symptoms such as proteinuria, glomerular integral, interstitial inflammation, vasculitis,crescent/necrosis and the like of the mice in the treatment group are obviously improved.

The invention provides HB-NC4 recombinant protein and a preparation method and application thereof, and belongs to the technical field of biological medicines, the recombinant protein is formed by recombination of an N-terminal non-collagen structural domain 4 and an HB heparin binding structural domain of NC4 human collagen IX. The amino acid residue sequence of the recombinant protein is as shown in SEQ ID NO. 1. A nucleotide sequence for coding the recombinant protein is shown as SEQ ID NO.3 or a sequence with genetic code degeneracy. In the nucleotide sequence for coding the recombinant protein, the nucleotide sequence for coding the heparin binding domain is as shown in SEQ ID NO.4, and the nucleotide sequence for coding the N-terminal non-collagen domain 4 of the human collagen IX is as shown in SEQ ID NO.5 or has a sequence with genetic code degeneracy. The invention also discloses the preparation method of the HB-NC4 fusion protein. The HB-NC4 fusion protein retains the complement inhibition activity of the N-terminal domain 4 of collagen IX, can directly target cartilage and retain the complement inhibition activity, and the targeting property and retention time of the fusion protein are greatly improved.

Compstatin analogues having improved binding and complement-inhibiting activity as compared to the 13 amino acid compstatin peptide (ICWQDWGHHRCT (cyclic C2-C12)) are described, in particular compstatin analogues that additionally possess useful physicochemical properties. The analogues have a thioether bond rather than a disulfide bond between the side chains of the f residues corresponding to cysteines 2 and 12 of compstatin which may increase stability. The analogues may also have an isoleucine residue at position 3 in place of the wild type valine residue, which provides compstatin peptides with improved binding and complement-inhibiting activity and also enables the introduction of other modifications, for example modifications that are capable of increasing solubility, such as the introduction of charged or polar amino acids at position 9 and/or the introduction of N- and/or C-terminal sequences.

The invention discloses a fusion protein of a complement receptor 2 mutant and a complement inhibitor CD 59 and application thereof to preparing autoimmune disease treating drugs. The complement receptor 2 mutant is a molecular modified body obtained through computer modelling and amino acid replacement and is higher in ligand binding and dissociation rate and ligand binding force compared with wild sequences. Biological distribution test shows that the fusion protein can be highly concentrated at arthritic parts after entering mouse models with rheumatoid arthritis and achieve significant anti-adhesion/anti-inflammatory targeted inhibition effects; when applied to treating MRL/lpr (Murphy Roths large/lymphoproliferation) mice with systemic lupus erythematosus, the fusion protein can significantly improve the survival rate of the mice, and symptoms of the mice of a treatment group such as proteinuria, glomerular score, interstitial inflammation, vasculitis and crescent glomerulonephritis/necrosis can be significantly improved.

The invention discloses a targeted complement inhibitor fusion protein C3d-ScFv-CD59 of a single-chain antibody of a human anti-complement C3d molecule and a complement inhibitor CD59. The fusion protein has excellent antigen binding activity, and in-vitro inhibition experiments show that C3d-ScFv-CD59 has a more obvious inhibition effect corresponding to a single effector molecule CD59, and the effect is realized by identifying that the C3d component in a complement activation region plays a complement inhibition role. The C3d-ScFv-CD59 is used for treating influenza/bacteria co-infected mice, the survival rate is obviously increased, lung lesions are obviously relieved, the targeted complement inhibition effect is obvious, and the C3d-ScFv-CD59 has an obvious treatment effect compared with the single effector molecule CD59, and it proves that the fusion protein provided by the invention has an excellent application prospect in preparation of drugs for treating influenza virus and bacteria co-infected pneumonia.

The invention discloses a single-chain antibody of a human anti-complement C3d molecule and a fusion protein of the single-chain antibody and a complement inhibitor CD55. The antibody and the fusion protein have excellent antigen binding activity, in-vitro inhibition experiments show that C3d-ScFv-CD55 has an obvious inhibition effect corresponding to a single effector molecule CD55, and the effect is realized by identifying that the C3d component in a complement activation region plays a complement inhibition role. The targeted complement inhibitor C3d-ScFv-CD55 is used for treating influenza/bacteria co-infected mice, the survival rate is obviously increased, lung lesions are obviously relieved, the targeted complement inhibition effect is obvious, and the targeted complement inhibitor C3d-ScFv-CD55 has an obvious treatment effect compared with the single effector molecule CD55, and it proves that the fusion protein provided by the invention has an excellent application prospect in preparation of drugs for treating influenza virus and bacteria co-infected pneumonia.

The invention belongs to the technical field of biology, and particularly relates to a medicine for treating age-related macular degeneration, the medicine is a fusion protein composed of vascular endothelial growth factor inhibitory protein and complement inhibitory protein, and the medicine can be used for treating diseases caused by vascular endothelial growth factor and/or complement activation. The fusion protein can be administered in various modes, and the specific forms include but are not limited to recombinant protein, genes for directly delivering and coding the fusion protein through a nano material wrapping technology, and genes for directly delivering and coding the fusion protein through various virus vectors. The medicine disclosed by the invention belongs to gene therapy, can stably release the medicine, does not generate violent fluctuation of intraocular medicine concentration in a treatment cycle, only needs to be injected once, reduces the frequency of patients going to hospitals, can prevent wet macular degeneration from being converted into dry macular degeneration, and eliminates treatment hidden dangers.

The invention belongs to the field of an immunological detection method and discloses an ELISA (Enzyme-Linked Immunosorbent Assay) detection method of an activation level of a complement system. Aiming at classic, replaced and mannose activation ways of the complement system, three different activators are respectively used for covering a 96-pore high-adsorbability elisa plate to activate the complement system in vitro; a polyclonal anti-complement antibody is used as an intermediate for capturing an activated complement; and anti-IgG-HRP (Horseradish Peroxidase) is used as an ELISA detection antibody so as to reflect an activation condition of the complement system. According to the ELISA detection method disclosed by the invention, a two-step method is used as an amplification system to replace a traditional three-step method. The method disclosed by the invention consumes less time and is simple in operation process; and a step of marking the antibody by digoxin can be saved so that an experiment is more convenient. The method disclosed by the invention makes up the detects that an existing hemolytic test cannot determine the activation conditions of a complement mannose way, and is particularly suitable for detecting the inhibition effect on the complement system by medicines; and a brand-new rapid and efficient complement inhibition agent in-vitro screening method is established.