The invention relates to novel conjugating reagents capable of reaction with at least one nucleophile present in a peptide or protein, which contain at least one leaving group which is lost on reaction with said nucleophile, in which the leaving group includes a portion —(CH.sub.2CH.sub.2O).sub.n—, in which n is a number of six or more; and novel processes for the preparation of conjugates containing peptides or proteins made using such reagents.

The present invention discloses thiourea-containing dendrimers and thiourea-containing hyperbranched polymers, and respectively a preparation method for the thiourea-containing dendrimer and a preparation method for the thiourea-containing hyperbranched polymer, and a thiourea-containing dendrimer and a thiourea-containing hyperbranched polymer having increased water solubility prepared by using the thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer as raw materials. Finally, disclosed are applications of the thiourea-containing dendrimers and the thiourea-containing hyperbranched polymers in the preparation of antitumor and antimicrobial drugs. The thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer have a significant growth inhibitive effect on solid tumors and low toxicity to normal tissues, and thus can be used for preparing drugs for treating malignant tumors. The thiourea-containing dendrimer and the thiourea-containing hyperbranched polymer also have a good antimicrobial effect on various bacterial strains and thus can be used for preparing antiviral or antibacterial drugs.

Provided herein is combination cancer therapy effected by administering a polymer-conjugated hyaluronidase, and a tumor-targeted taxane, and optionally a further chemotherapeutic agent such as a nucleoside analog. The combination therapy can be used in methods of treating cancers, and in particular solid tumor cancers.

The present invention provides a novel biomaterial which is a hybrid, self-assembling biopolymeric networked film that is functionalized through hydrophobic interactions with vesicles loaded with bioactive agents. The biomaterial compound is a polymeric network of hydrophobically modified chitosan scaffolds that is taken from solution and formed as a solid film. This solid state film is capable of hydrophobic interactions with the functionalized vesicles. The vesicles include one or more lamellar structures forming one or more nano-compartments that are capable of containing similar or alternative active moieties within. Use of the film results in a degradation of the chitosan scaffold thereby releasing the active moieties within the vesicles from the scaffold. Application of the current invention occurs through various delivery mechanisms and routes of administration as will be described herein.

The present invention provides a novel biomaterial which is a hybrid, self-assembling biopolymeric networked film that is functionalized through hydrophobic interactions with vesicles loaded with bioactive agents. The biomaterial compound is a polymeric network of hydrophobically modified chitosan scaffolds that is taken from solution and formed as a solid film. This solid state film is capable of hydrophobic interactions with the functionalized vesicles. The vesicles include one or more lamellar structures forming one or more nano-compartments that are capable of containing similar or alternative active moieties within. Use of the film results in a degradation of the chitosan scaffold thereby releasing the active moieties within the vesicles from the scaffold. Application of the current invention occurs through various delivery mechanisms and routes of administration as will be described herein.

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

Provided are a nucleic acid nanocarrier drug, a preparation method thereof, a pharmaceutical composition and an application thereof. The nucleic acid nanocarrier drug includes a nucleic acid nanoparticle carrier and a drug; and the nucleic acid nanoparticle includes a nucleic acid domain, the nucleic acid domain includes a sequence a, a sequence b and a sequence c, the sequence a includes a sequence a1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence a1, the sequence b includes a sequence b1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence b1, and the sequence c includes a sequence c1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence c1.

Provided are a nucleic acid nanocarrier drug, a preparation method thereof, a pharmaceutical composition and an application thereof. The nucleic acid nanocarrier drug includes a nucleic acid nanoparticle carrier and a drug; and the nucleic acid nanoparticle includes a nucleic acid domain, the nucleic acid domain includes a sequence a, a sequence b and a sequence c, the sequence a includes a sequence a1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence a1, the sequence b includes a sequence b1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence b1, and the sequence c includes a sequence c1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence c1.

Disclosed are methods of treating chronic nervous system diseases or injuries, e.g., chronic spinal cord injury, using Nogo receptor antagonists, including Nogo receptor-1 (NgR1) polypeptides, Nogo receptor-1 antibodies and antigen-binding fragments thereof, soluble Nogo receptors and fusion proteins thereof, and polynucleotides. Also disclosed are methods of noninvasively monitoring axonal growth during and after treatment with an axonal growth promoting agent.

The present invention relates to conjugates of an electron-donating heteroaromatic nitrogen or tertiary amine comprising drugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising said conjugates and the use of said conjugates as medicaments.