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Transdermal drug administration intensifier and its usage method

A technology for transdermal drug delivery and enhancer, which is used in pharmaceutical formulations, preparations for skin care, botanical equipment and methods, etc.

Inactive Publication Date: 2011-04-13
UNIV OF SCI & TECH OF CHINA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in vivo phage display methods have not been used to screen for transdermal peptides

Method used

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  • Transdermal drug administration intensifier and its usage method
  • Transdermal drug administration intensifier and its usage method
  • Transdermal drug administration intensifier and its usage method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 , In vivo phage display technology to screen peptides with skin penetration enhancing function

[0115] The library used to screen peptides with transdermal enhancing function was provided by New England Biolabs (Mass, MA), a library of heptapeptides containing disulfide bonds among three random peptide libraries (Ph.D.-C7C). Random fragments in this library are flanked by cysteine ​​residues that can be oxidized during phage assembly to form disulfide linkages, thus forming a cyclic peptide that interacts with the target. (Ph.D. TM -C7C Phage Peptide Display Kit [online], [purchased on 2005-09-01]. I learned the information on the Internet

[0116] http: / / www.neb.com / nebecomm / products / productE8120.asp >). This library contains more than two billion clones. Random peptides in the library are amino-terminal to the small coat protein pill, so five copies are expressed per phage particle. The position of the phage-expressed random sequence in the Ph.D.-C7C...

Embodiment 2

[0119] Example 2 , chemical synthesis of transdermal enhancers and their analogues

[0120] The peptides in this patent are all synthesized by Shanghai Jier Biochemical Company using the standard FMOC solid-phase synthesis method in an automatic peptide synthesizer (CS536-1381, CS Bio Co., Menlo Park, CA), and purified by HPLC to make the purity greater than 95 %, using a mass spectrometer (BIFLEX TM III, Bruker, Germany) to identify molecular weights.

[0121] The peptide synthesis procedure of the sequence ACSSSPSKHCG (TD-1, SEQ ID NO: 2) is as follows. The terminal amino acids alanine and glycine are derived from the M13 surface protein. TD-1 uses the standard FMOC solid-phase synthesis method, and the general manual synthesis steps are as follows: about 0.2 mmol Fmoc-Gly-Wang resin is added to the manual reaction tube (Peptides International), and DMF is added to allow it to expand for 2 hours. Then add 20% piperidine / DMF to react for 2min to remove the Fmoc protecti...

Embodiment 3

[0123] Example 3 , TD-1 inhibits the transdermal activity of PH-1

[0124] Male Wistar rats (180 g to 220 g) were housed in animal rooms with constant temperature (22°C), constant relative humidity (60%), and a fixed 12-h light / dark cycle, and they were free to take food and water. Anesthetize the mice with molasses (5 mg / kg, concentration 20%), and then use scissors to cut off the hair in the abdomen area of ​​about 3 cm × cm, taking care not to damage the skin (the mice with any visible scars are discarded). Display of TD-2 peptide (SEQ ID NO: 1) 10 12 PH-1 phage or control phage, the control phage is randomly picked from the library, and the coding sequence AP-1 (sequence number: 6), is placed in the shearing area, and spreads it on the whole area with the side of the pipette tip . One hour later, blood was drawn from the tail vein and titrated according to the manufacturer's instructions.

[0125] Tested in Wistar rats, it was shown that phages expressing TD-1 pepti...

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Abstract

The invention relates to an internal bacteriophage display technique for recognizing the polypeptide with strengthen transdermal feeding ability. The invention also provides a relative strengthened polypeptide, which can accelerate and / or strengthen the transdermal feeding ability of any medicine. The invention also discloses a compound with said polypeptide, and the relative application method.

Description

technical field [0001] The present invention is primarily concerned with non-diffused transdermal or transdermal administration. In particular, the present invention relates to a method of identifying and screening polypeptides that enhance and / or facilitate transdermal delivery of any therapeutic agent and / or drug, including any polypeptide, protein, Polynucleotides, oligonucleotides (antisense oligonucleotide preparations), ribozymes, double-stranded RNAs (dsRNAs), small interfering RNAs (siRNAs), RNA interference, gene therapy vectors, vaccines and any routine drug. The present invention also relates to compositions and methods for enhancing the transdermal or transdermal delivery of these therapeutic agents and drugs. Background technique [0002] As the largest organ in the human body, the skin provides a painless and suitable vehicle for systemic drug delivery (Prausnitz et al., 2004, Nature Rev. Drug Discov. 3: 115; Thomas and Finnin, 2004, Drug Discov. Today 9 : 6...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61K9/70A61K8/64C12N15/12C12N15/31A61Q19/00A61Q7/00A61M37/00
Inventor 温龙平陈勇平沈媛媛郭欣
Owner UNIV OF SCI & TECH OF CHINA
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