38 results about "Complement Inhibitors" patented technology

Modulation of the complement system represents a therapeutic modality for numerous pathologic conditions associated with complement activation. In a strategy to prepare complement inhibitors that are targeted to sites of complement activation and disease, compositions comprising a complement inhibitor linked to complement receptor (CR) 2 are disclosed. The disclosed are compositions can be used in methods of treating pathogenic diseases and inflammatory conditions by modulating the complement system.

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.

A method for preventing or treating tissue damage associated with ischemia-reperfusion injury and thoraco-abdominal aortic aneurysm (TAAA) repair by administering a tissue damage preventing or treating amount of a complement inhibitor to a patient likely to suffer from or suffering from tissue damage associated with ischemia-reperfusion injury or TAAA repair. The complement inhibitors are preferably antibodies that bind to and inhibit complement proteins involved in the formation of the membrane attach complex, preferably antibodies that inhibit MBL, MASP1, MASP2, and MASP3 in the lectin pathway. The complement inhibitors can be used alone or in combination to decrease the morbidity and mortality caused by tissue damage associated with ischemia-reperfusion injury or TAAA repair.

The present disclosure is directed to screening, diagnosing and treating patients having, or suspected of having, rheumatoid arthritis. Levels of glucose-6-phophate isomerase or antibodies to glucose-6-phophate isomerase are assayed in test subjects or populations to determine susceptibility to, or existence of, an antibody mediated form of rheumatoid arthritis in such test subjects or populations. The results of the assays provide guidelines for therapeutic intervention with complement inhibiting agents.

This invention provides, inter alia, a complement-inhibitor-based treatment plan coupled with a risk evaluation and management strategy (“REMS”) and a safety support program (“SSP”) for reinforcing the REMS. The REMS and SPP are implemented using one or more computer devices with software tools programmed to enforce conditions of the REMS and/or prompt follow-ups by registered nurses enrolled in the SSP. The software tool(s) determines whether a prescriber requesting the complement inhibitor has agreed to abide by the REMS, and can prompt a provider of the complement inhibitor to provide updated educational materials to the prescriber at predetermined times or intervals, to monitor the prescriber for compliance with the REMS, and/or to monitor patients for signs of adverse events. Using exemplary embodiments described herein, a risk of adverse events (especially, but not limited to, meningococcal infections) can be managed and an incidence of the adverse events can be reduced.

The invention provides the application of caffeoylquinic acid and its derivatives in the preparation of anti-complement drugs. The present invention extracts and separates the caffeoylquinic acid compounds obtained from Shamrock, through in vitro experiments, it is confirmed that the cell hemolysis caused by the activation of the classic pathway of the complement system is inhibited, indicating that there is an anti-complement effect. The activity is stronger than that of the total extract of S. sageris, and it is a kind of good complement inhibitor, which can be used to prepare new anti-complement drugs and treat various diseases caused by abnormal activation of complement, and has low effective concentration and low toxicity. The drug is safe, the source of raw materials is abundant, and it has great clinical application value. Caffeoylquinic acid and its derivatives are shown in the following structural formula I: Formula I wherein R1, R2, R3, or R4 can be the same or different, and they are H or caffeoyl respectively, provided that they cannot be H at the same time; R5 is H , CH3, CH2CH3 or CH2CH2CH2CH3.

Methods for treating, preventing or delaying onset of polyp formation and subsequent colon cancer are disclosed. The methods involve administration of a complement inhibitor to inhibit C5a receptor signaling in the tumorigenic or pre-tumorigenic tissue.

Methods for reducing rejection of pancreatic islet cells transplanted into a subject are disclosed. The methods involve transplanting pancreatic islet cells into a subject in the presence of a complement inhibitor, alone or combined with dextran sulfate.

The invention discloses an anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 and application thereof. The invention aims to provide an anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 with specific targeting and the application thereof in preparing medicaments for treating systemic inflammations. The anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 is a fusion protein obtained by connecting the amino terminal of the anti-P-selectin single-chain antibody ScFv with the complement inhibitor CD59 by using a connecting peptide. The experiment proves that the ScFv-CD59 can obviously improve the efficiency of inhibiting the complement-mediated cell cracking, can achieve high-degree accumulation at the immune injury part, can obviously inhibit the occurrence and degeneration of inflammations and can obviously reduce the side effect of infection caused by the complement inhibitor. Therefore, the ScFv-CD59 can be used as an active ingredient to be prepared into a novel gene engineering targeted protein medicament with a targeted P-selectin complement inhibitor for treating inflammations. The invention plays an important role in the pharmaceutical field and has wide application prospects.

The invention discloses an application of a targeted complement inhibitor in preparation of drugs for improving brain death donor livers. The application of the targeted complement inhibitor in preparation of the drugs for improving the brain death donor livers is characterized in that a complement receptor 2 (CR2) is utilized to connect a membrane binding regulatory factor Crry; with targeted binding of the CR2 to complement activation and local injury, the membrane-binding regulatory factor utilized to regulate different stages of complement cascade, and a mouse brain death model established, the changes of the liver functions between a CR2-Cryy treatment group and a control group are compared; results indicate that the targeted complement inhibitor CR2-Crry is effective in improving donor liver injury after brain death and can reduce liver inflammatory response, oxidative stress damage and hepatocyte apoptosis. The role of this complement inhibitor in improving donor liver functionafter brain death is further confirmed by complement knockout mice.

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 belongs to the field of preparation of traditional Chinese medicines and relates to a benzo-macrolactam indole alkaloid, indigo naturalis alkaloid C, and an application thereof in preparation of anti-complement medicines. In the invention, the benzo-macrolactam indole alkaloid, indigo naturalis alkaloid C, is separated from powder of indigo naturalis, wherein the compound has a novel and unique structure and is formed by complexing two 3-carbonyl indole groups on benzo-macrolactam. A modern pharmacological experiment proves that the compound has strong inhibition effects on both a classic pathway and a bypass pathway of a complement system, wherein the CH50 value and the AP50 value of the compound are respectively 0.018 +/- 0.004 mg/ml and 0.042 +/- 0.014 mg/ml. The compound can be used for preparing a complement inhibitor.

The invention belongs to the field of traditional Chinese medicine pharmacy and relates to a sterol lactam compound and use thereof in preparation of anticomplement drugs. According to the sterol lactam compound and the use thereof, the sterol lactam compound, i.e., puffball lactam is obtained through being separated from fruiting bodies of puffballs, and the compound is ergosterol of B-ring lactam; and proven by anticomplementary activity evaluation tests, the sterol lactam compound, i.e., puffball lactam has a relatively high inhibiting effect on activation of a classical pathway and alternative pathway of a complement system, has the CH50 value of 0.032+/-0.007mg/ml and has the AP50 value of 0.067+/-0.009mg/ml. The compound can be used for preparing complement inhibitors.

The invention presents a swine cell not expressing α-1,3-galactosyl transferase and expressing human complement inhibitor and/or human N-acetyl glucosaminyl transferase III; a method of selecting the same; and a swine for xenotransplantation. The swine for xenotransplantation of the invention is very useful in inhibiting the acute rejection characteristic to xenotransplantation because it does not express α-Gal antigen but inhibits the progress of a complement reaction, if unexpectedly induced, and/or expresses little xenoantigen other than α-Gal antigen.

The invention belongs to the field of traditional Chinese medicine pharmacy and relates to an application of carbazole-type indole alkaloids in preparation of anti-complement medicines. The novel carbazole-type indole alkaloid compounds are separated from powder of indigo naturalis and have novel and unique structures. The invention, for the first time in nature, discloses the carbazole-type indole alkaloids in which a substituted group is introduced to a sixth locus. The carbazole-type indole alkaloids include the following two compounds: (1) 1-(5,7-dihydroxypyridino[3,2-b:5,6-b']bisindole-6-ethane-2-one and (2) N-(2-hydroxyphenyl)-5,7-dihydroxypyridino[3,2-b:5,6-b']-bisindole-6-formamide. A modern pharmacological researching method proves that the compounds have strong inhibition effects on both a classical pathway and a bypass pathway of a complement system, wherein the CH50 values of the compound (1) and the compound (2) are respectively 0.024 +/- 0.007 mg/ml and 0.032+/- 0.009 mg/ml while the AP50 values are respectively 0.056 +/- 0.010 mg/ml and 0.072+/- 0.014 mg/ml. The compound is used for preparing a complement inhibitor.