Shanghai Pulmonary Hospital

International Business Machines Corporation

Xian He

Huiping Li

Shanmei Wang

Hongwei (Nick) Dai

Zhaofang Yin

Chen Du

Jian Niu

Present invention relates to a human lung tissues-active targeting immune nanoliposome of methylprednisolone, wherein, nanoliposomes loaded with therapy drugs is covalently coupled with nanobodies against human pulmonary surfactant protein A. Wherein, the therapy drug is methylprednisolone sodium succinate, the nanoliposome consists of phospholipids, cholesterols and long cycling materials. The molar ratio of the methylprednisolone sodium succinate to phospholipids within the nanoliposome is 0.30-0.45. Present invention successfully provides a new human lung tissues targeting hormone preparation, wherein, the nanoliposome serves as a carrier, the nanobody against human pulmonary surfactant protein A serves as a specific lung tissue targeting ligand, methylprednisolone sodium succinate serves as a therapy drug. In accordance with present invention, an efficient, stable human lung tissues-active targeting immune nanoliposome, with specific active lung targeting, is prepared.

Human lung tissues-active targeting immune nanoliposome of methylprednisolone and a method for producing the same

The present invention relates to the field of biochemistry and pharmaceutical technologies. The present invention provides nanobodies that bind to human pulmonary surfactant protein A (SP-A) as well as the preparing methods and use of the same. The nanobody comprise an amino acid sequence having the formula of Q(x)LVESGG(x)V(x)G(x)SL(x)LS(x)E(x)KG(x)S(x)T(x)Y(x)C(x)S(x)V(x)R; wherein x is amino acid; n2&#x2dc;n6 are positive integers; 1&#x2266;n2&#x2266;21; 1&#x2266;n3&#x2266;19; 1&#x2266;n4&#x2266;50; 1&#x2266;n5&#x2266;22; 1&#x2266;n6&#x2266;8. The present invention take fresh frozen sections of lung as antigen, gene sequences with high affinity with hSP-A were obtained by constructing an SP-A antibody library and affinity selection, and nanobodies with high affinity and small molecular weight were obtained by induced expression of the gene sequences through a prokaryotic expression vector. Immunohistochemistry and in vivo imaging in nude mice showed the nanobodies have high specificity for targeting lung tissue.

Lung-targeting nanobodies against human pulmonary surfactant protein A and a method for producing the same

Disclosed are a method and system for improving timing closure in chip design. The method comprises: identifying a critical timing path in a chip design pattern, wherein a timing window of the critical timing path is smaller than a predetermined timing window; determining a variation of each segment of the critical timing path, wherein the variation indicates uncertainty of delay of a device and/or a wire caused by one or more factors; and changing at least one segment of the critical timing path based on the variation of each segment of the critical timing path to enlarge the timing window of the critical timing path. The method and system may enlarge a timing window of a critical timing path by reducing the variation thereof, thereby achieving timing closure in the chip design pattern.

Timing closure in chip design

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Shanghai, China

Xian He