WO2010051667A1 - Compositions pharmaceutiques comprenant des nanotubes de peptide cyclique et utilisations de celles-ci - Google Patents

Compositions pharmaceutiques comprenant des nanotubes de peptide cyclique et utilisations de celles-ci Download PDF

Info

Publication number
WO2010051667A1
WO2010051667A1 PCT/CN2008/073015 CN2008073015W WO2010051667A1 WO 2010051667 A1 WO2010051667 A1 WO 2010051667A1 CN 2008073015 W CN2008073015 W CN 2008073015W WO 2010051667 A1 WO2010051667 A1 WO 2010051667A1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
cyclic peptide
nanotube
drug
nanotubes
Prior art date
Application number
PCT/CN2008/073015
Other languages
English (en)
Chinese (zh)
Inventor
吴伟
陈健
邱怡婷
张蓓
卢懿
Original Assignee
复旦大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 复旦大学 filed Critical 复旦大学
Publication of WO2010051667A1 publication Critical patent/WO2010051667A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a pharmaceutical composition, and more particularly to a cyclic peptide nanotube pharmaceutical composition and use thereof.
  • D,L-amino acids are alternately linked to form a closed loop peptide.
  • the cyclic peptide adopts a planar configuration.
  • the substituent on the X-carbon is parallel to the annulus and is directed outside the ring along the radius of the ring.
  • the carbonyl group and the amino group on the backbone of the main chain are perpendicular to the torus.
  • the hollow cyclic peptide molecule passes through the C in the main chain skeleton acylamino group.
  • N-H form an intermolecular hydrogen bond network in a ⁇ -sheet fashion and accumulate into a tubular structure with a stable nature, open ends, and a molecular size ranging from a self-assembled cyclic peptide nanotube (J Am Chem Soc, 1998). , 120 (35) : 8949. )
  • This ⁇ -sheet can be parallel or parallel, but computer analysis and experiments show that the ⁇ -sheet of cyclic peptide nanotubes designed based on this principle Hydrogen bonding is thermodynamically preferred to the counter-parallel structure (Ma t Sc i Eng C, 1997, 4 (4): 207.).
  • nanotubes in this way has two outstanding advantages: 1 can pass the control loop The number of peptide amino acids is used to modulate the pore size of the nanotube; 2 the outer wall properties of the nanotube can be altered by controlling the amino acid species of the cyclic peptide.
  • the pore size of the cyclic peptide nanotube can be adjusted by changing the number of amino acids of the cyclic peptide, but the size of the cyclic peptide is too small, and a large tension in the ring is disadvantageous for forming a hydrogen bond network between the subunits; when it is too large, due to the looseness of the ring skeleton Unable to self-assemble into a stable tubular structure (J Am Chem
  • the amino acid residue sequence of the D,L-cyclic peptide should be favorable for its stable spatial structure, and the nature of the amino acid in the cyclic peptide has an important influence on various self-assembly under different conditions.
  • the advantage of cyclic peptide nanotubes is that the surface properties of the nanotubes can be adjusted by selecting suitable amino acids, which allows us to design cyclic peptides of different amino acids according to different uses, which can self-assemble in different chemical environments. Nanotubes of different nature.
  • lipid bimolecular membrane with a low conductance constant facilitates self-assembly of the cyclic peptide therein.
  • Ghadi rl verified this possibility for the first time through a liposome model and a series of spectroscopic methods.
  • a sufficient concentration of cyc lo [- (Trp-D- Leu) 3 _G ln_D_Leu_] is added to the suspension of liposomes, and the hydrophobic side chains of the cyclic peptides allow them to rapidly insert into the lipid bilayer and rely on the molecule
  • the inter-hydrogen bond is deposited in the lipid film to an inner diameter of about 0.75.
  • the activity of the cyclic peptide nanotubes for K+ and Na+ transport was 2. 2 X 10 ⁇ 1. 8 X 10 7 ions - s" 1 , which is the natural state under the same experimental conditions, by recording the ion single-channel current with a micro-film clamp. The analog is 3 times higher than the gramicidin A.
  • Synthetic D,L_ ⁇ -cyclic peptides can be inserted into the bacterial cell membrane and deposited in the lipid membrane to form a hollow tubular channel. Both in vitro and in vivo tests have shown that these cyclic peptide nanotubes can effectively kill methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and other pathogenic bacteria. (Na ture, 2001, 412 (26) : 452. ). The advantage of self-assembling cyclic peptide nanotubes as novel antibiotics is that the cyclic peptides are flexible in design, easy to synthesize, and stable to proteases.
  • cyclic peptide nanotubes do not produce chemical effects, but only use nano-sized pores on bacterial cell membranes to exert antibacterial activity. This unique mechanism of action shortens sterilization time and reduces resistance. The production of medicinal properties.
  • cyclic peptide nanotubes In view of the self-assembly of cyclic peptides on the cell membrane to form nanotubes, small molecules with a diameter smaller than their inner diameter are allowed to diffuse into the cells by passive diffusion. Therefore, this property of cyclic peptide nanotubes can be utilized to construct a small molecule drug delivery system to make small molecules.
  • the drug rapidly enters the cell at a high concentration, enhances its cytotoxic effect, and synergizes with the cyclic peptide nanotubes, and has potential application in tumor treatment and infection against pathogens such as cells and viruses.
  • the cyclic peptide nanotube van der Waals inner diameter is 0. 75-1. 3nm, the tube length is 10-100nm, the basic constituent unit of the cyclic peptide nanotube is a cyclic peptide, and the cyclic peptide is composed of 8, 10, 12 amino acids.
  • the diameter of the drug molecule is smaller than the inner diameter of the cyclic peptide nanotube van der Waals.
  • the cyclic peptide in the cyclic peptide nanotube is formed by alternately covalently bonding the same amount of D-form and L-form amino acid, and the drug molecule is a hydrophilic drug.
  • amino acid sequence of the cyclic peptide in the cyclic peptide nanotube is SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7.
  • SEQ ID NO: 8 SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: : SEQ ID NO: 16 , SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 2 SEQ ID NO: 22, SEQ ID NO: 23 or SEQ ID NO: 24, wherein the drug is selected from the group consisting of 5-fluorouracil, flucytosine, tegafur, salicylic acid, p-aminosalicylic acid, cisplatin, carboplatin, nitrogen mustard, cyclophosphamide, and different Cyclophosphamide, guanidine, glyphosate, melphalan, carmustine, lomustine, semustine, nimustine, dopamine, isoniazid, isothiosulphonamide, ethylamine Butanol, ribavirin, zidov
  • the amino acid sequence of the cyclic peptide in the cyclic peptide nanotube is as shown in SEQ ID NO: 23 or SEQ ID NO: 24, and the drug is selected from the group consisting of 5-fluorouracil, tegafur, cisplatin or carboplatin.
  • the technical solution adopted by the present invention is: a cyclic peptide nanotube pharmaceutical composition for preparing a medicament for treating a tumor disease, a bacterial infection disease or a virus infection disease, the cyclic peptide nanotube
  • the pharmaceutical composition consists of a cyclic peptide nanotube and a drug.
  • the cyclic peptide nanotube van der Waals inner diameter is 0. 75-1. 3nm, the tube length is 10-100nm, the basic constituent unit of the cyclic peptide nanotube is a cyclic peptide, and the cyclic peptide is composed of 8, 10, 12 amino acids.
  • the diameter of the drug molecule is smaller than the inner diameter of the cyclic peptide nanotube van der Waals.
  • the cyclic peptide in the cyclic peptide nanotube is formed by alternately covalently bonding the same amount of D-form and L-form amino acid, and the drug molecule is a hydrophilic drug.
  • the amino acid sequence of the cyclic peptide in the cyclic peptide nanotube is SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7.
  • SEQ ID NO: 8 SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: : SEQ ID NO: 16 , SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 2 SEQ ID NO: 22, SEQ ID NO: 23 or SEQ ID NO: 24, wherein the drug is selected from the group consisting of 5-fluorouracil, flucytosine, tegafur, salicylic acid, p-aminosalicylic acid, cisplatin, carboplatin, nitrogen mustard, cyclophosphamide, and different Cyclophosphamide, guanidine, glyphosate, melphalan, carmustine, lomustine, semustine, nimustine, dopamine, isoniazid, isothiosulphonamide, ethylamine Butanol, ribavirin, zidov
  • the amino acid sequence of the cyclic peptide in the cyclic peptide nanotube is as shown in SEQ ID NO: 23 or SEQ ID NO: 24, and the drug is selected from the group consisting of 5-fluorouracil, tegafur, cisplatin or carboplatin.
  • the self-assembly of cyclic peptide nanotubes on the cell membrane can establish channels through the inside and outside of the cell, mediating the transmembrane transport of ions such as H + , 3 ⁇ 4+, K+, etc., thus breaking the intracellular and extracellular ion balance, leading to cell death, thus having antibacterial and antibiotic resistance.
  • ions such as H + , 3 ⁇ 4+, K+, etc.
  • the role of the virus It has also been found that cyclic peptide nanotubes can transport transmembrane transport of vital molecules, glucose and glutamate.
  • the inventors of the present invention have found through research that self-assembled cyclic peptide nanotubes can mediate transport of small molecule drugs through cell membranes at a rate greater than that of small molecule drugs without diffusion into the cells via nanotubes.
  • the combination of cyclic peptide nanotubes and drugs has a synergistic antitumor effect.
  • a nanotube drug delivery system formed by self-assembly of a cyclic peptide in the present invention, comprising a cyclic peptide nanotube and a drug The things are made up together.
  • the cyclic peptide nanotubes Based on the hydrophobic nature of the cyclic peptide nanotubes, the cyclic peptide nanotubes self-assemble in the phospholipid bilayer of the cell membrane, and the thickness of the tube long-term cell membrane or pathogen shell is between 10-100 nm, preferably between 20-50 nm.
  • the basic constituent unit of the cyclic peptide nanotube is a cyclic peptide, and the cyclic peptide adopts a mesostructure, and the intermolecular self-assembly through the hydrogen bonding layer forms a nanotube, in order to facilitate the formation of intermolecular hydrogen bonds and form a stable nanotube, the cyclic peptide
  • the number of amino acid residues is 8 - 12, and the D and L amino acids are alternately covalently combined.
  • the inner diameter of the cyclic peptide nanotubes is 0.75-1.3 nm, limited by the number of amino acid residues of the cyclic peptide.
  • the amino acid sequence forming the cyclic peptide nanotube may be selected from the group consisting of S P S -, SWFKTKSK-,
  • the synthesis of the cyclic peptide of the present invention can be carried out by a general-purpose solid phase or liquid phase synthesis method in a general-purpose reactor or a solid phase synthesizer.
  • the synthesized cyclic peptide is separated by preparative liquid phase and has a purity of more than 95%.
  • a liquid phase synthesis route of yvyvyvy ⁇ Q- is given in the embodiment of the present invention.
  • the transmembrane transport mode of the drug through the cyclic peptide nanotubes is passive diffusion, which is limited by the inner diameter of the cyclic peptide, and the molecular diameter of the drug should be smaller than the inner diameter of the cyclic peptide nanotube.
  • the inner diameter of the nanotubes formed by the cyclic decapeptide yvyvyvy ⁇ Q- provided by the present invention is 1. Onm, which allows the molecular diameter to be less than 1.0.
  • the drug having a molecular diameter of less than 1.3 nm is allowed to pass through. Considering that the larger the molecular diameter, the greater the resistance encountered during penetration, the molecular diameter should be significantly smaller than the inner diameter of the nanotube.
  • the on-line peptide nanotube drug delivery system wherein the diameter of the drug molecule is less than 1. 3 nm, preferably less than 1. Onm.
  • the cyclic peptide nanotube drug delivery system of the present invention is suitable for use in a plurality of cases in which small molecule drugs are transmembrane-transported via a nanotube, and the selection of the drug is not limited to its therapeutic purpose. From the perspective of killing cells and pathogens, the present invention is applicable to antitumor drugs, antibacterial agents, and antiviral agents. The scope of application can be extended in accordance with the technical principles of the present invention.
  • the drug for the cyclic peptide nanotube drug delivery system of the present invention is selected from the group consisting of 5-fluorouracil, flucytosine, tegafur, salicylic acid, p-aminosalicylic acid, cisplatin, carboplatin, nitrogen mustard, cyclophosphamide, Isophosphoramide, guanidine, glycolysate, melphalan, carmustine, lomustine, semustine, nimustine, dopamine, isoniazid, isothiazepine, B Aminobutanol, ribavirin, zidovudine, and metronidazole. It is especially selected from the group consisting of 5-fluorouracil, tegafur, cisplatin and carboplatin.
  • Loop effector nanotubes mediate the effect of small molecule drugs across liposome artificial phospholipid bilayer membrane transport in embodiments of the invention.
  • the liposome artificial phospholipid bilayer membrane is recognized as the best model for simulating cell membranes and is suitable for use in evaluating the drug delivery system of the present invention.
  • the transmembrane transport effects of hydrogen ion, 5-fluorouracil, tegafur, and cisplatin were evaluated in the order of different cyclic peptides, and the results showed that hydrogen ions or small molecule drugs increased with the amount of cyclic peptide. The transfer rate is accelerated.
  • the molecular diameter of cytarabine is 1.
  • a human liver cancer BEL-7402 cell line was selected, and the sensitivity of the 5-FU to the tumor cell membrane was examined.
  • the tumor cell line was seeded in a 96-well plate at 3000 cells/well. After 24 hours, a medium containing a certain concentration of CP and 5-FU was added for 48 hours, and the cytotoxicity of the drug was detected by MTT assay. The results showed that after the cyclic peptide (64 g/ml) was applied to human hepatoma BEL-7402 cell line, the IC50 of 5-FU decreased from 47.93 ⁇ g/ml to 25.02 g/ml.
  • cyclic peptide can self-assemble on the tumor cell membrane to form a cyclic peptide nanotube, and mediate the external small molecule drug 5-FU to rapidly enter the tumor cell through the channel to produce cytotoxicity.
  • the pharmaceutical composition of the present invention uses cyclic peptide nanotubes as transmembrane artificial nanochannels to allow small molecule drugs to enter cells by passive diffusion.
  • the present invention explores new medical uses of cyclic peptide nanotube pharmaceutical compositions.
  • the drug rapidly enters the cell at a high concentration, improves its cytotoxicity, and synergizes with the cyclic peptide nanotubes, and has potential application in tumor treatment and infection against pathogens such as bacteria and viruses.
  • Figure 1 Structural formula of cyclic decapeptide eye 10 [LWLWLWLQ ].
  • Figure 2 is a synthetic route diagram of cyclodecapeptide cyclo [LWLWLWLQ].
  • Figure 3A Light microscopy (600x) of a bundle of cyclic peptide nanotubes.
  • Figure 3B Transmission electron microscopy (2000 times) of bundled cyclic peptide nanotubes.
  • FIG 4 Loop peptide nanotubes mediate hydrogen ion (H+) transport across the artificial lipid membrane.
  • Loop peptide nanotubes mediate the transport of 5-FU across artificial lipid membranes.
  • Loop peptide nanotubes mediate transport of cisplatin across artificial lipid membranes.
  • Cyclic peptide nanotubes mediate the transport of tegafur across artificial lipid membranes.
  • Peptide nanotubes mediate transport of glucosinolates across artificial lipid membranes.
  • the c c o wyvyvy ⁇ Q] was synthesized by a solid-liquid phase binding method, and the van der Waals inner diameter of the cyclic peptide was 1. Onm, and its structural formula is shown in Fig. 1.
  • the self-assembly behavior of cyclic peptide nanotubes was observed in a solvent.
  • the l-decyl peptide 1 mg was placed in a 1.5 ml centrifuge tube, and dissolved in 0.5 ml of 1% TFA/CHC 1 3 , and the crystal precipitation was observed by standing. After standing for several hours or more than ten hours, it was gradually observed that short needle crystals were precipitated in the solution. When the degree of crystallization was maximized, centrifugation (l OOOOrpm, l Omin), the organic solvent was removed, and the resulting precipitate was suspended with an appropriate amount of purified water for further analysis.
  • the formed cyclic peptide nanotubes were observed by optical eigenoscopy and transmission electron microscopy as shown in Fig. 3A and Fig. 3B.
  • the observed cyclic peptide nanotubes were bundled and formed into a long rod shape.
  • Liposomes were prepared by reverse phase evaporation and the drug was 5-fluorouracil.
  • the preparation process is as follows: Take phospholipid (purity > 80%) 60mg, cholesterol 15mg, dissolve in 6ml CHC1 3 , add 2ml 5mg / ml drug / PBS solution; use ultrasonic probe for phacoemulsification, ultrasonic parameters: super 3s, stop ls, 40 Times, power 150W; The uniformly stable W/0 emulsion prepared was transferred to a round bottom flask and removed by rotary evaporation ( 3 ⁇ 4 (1 3 gel), parameters: water bath temperature 30 ⁇ 2 ° C, vacuum 0.07 - 0.08MPa; adding 1.5-2ml PBS solution for hydration, to obtain a drug liposome suspension, parameters: water bath temperature 30 ⁇ 2 ° C, vacuum degree 0.09-0.
  • cyclic peptide nanotubes mediate H+ transmembrane transport and alter the pH of the aqueous phase in the liposome, resulting in changes in the fluorescence intensity of the system.
  • the cyclic peptide nanotubes mediate the transport of hydrogen ions (H+) across the artificial lipid membrane, as shown in Figure 4. As the concentration of cyclic peptide increases, the transport speed of hydrogen ions accelerates. .
  • 5-fluorouracil (5-FU) transport investigation Take 1 ml of 5-FU liposome, put into dialysis bag (3.5kD), add 25 ⁇ of different concentrations of cyclic peptide/DMF solution (cyclopeptide concentration: Omg/ml, lmg/ml, 2mg/ml, 4mg/ Ml), placed in an Erlenmeyer flask containing 30 ml of PBS (pH 7.3) buffer, shaken at 100 rpm, 37 ° C water bath, release for 90 min, sample every 3 min, 40 ⁇ l each time, repeat each sample 6 Samples.
  • cyclic peptide/DMF solution cyclopeptide concentration: Omg/ml, lmg/ml, 2mg/ml, 4mg/ Ml
  • PBS pH 7.3
  • Cisplatin (DDP) translocation inspection
  • cyclic peptide/DMF solution cyclopeptide concentration: Omg/ml, lmg/ml, 2mg/ml, 4mg/ml
  • dissolution cup containing 50 ml of 0.2% NaCl
  • stirred by a small paddle, lOO rpm, 37 ° C water bath released for 90 min, sampled every 5 min, 0.5 ml each time, 5 samples were repeated for each batch.
  • the samples were measured by graphite furnace atomic absorption spectrometry.
  • the percent release is plotted against time t, which gives the cyclic peptide nanotubes mediated transport of cisplatin across the artificial lipid membrane, as shown in Figure 6.
  • time t which gives the cyclic peptide nanotubes mediated transport of cisplatin across the artificial lipid membrane, as shown in Figure 6.
  • the transmembrane transport rate of cisplatin is low, and as the amount of cyclic peptide increases, the transport rate increases.
  • the percent release is plotted against time t, which results in cyclic peptide nanotube-mediated translocation of Ara-C across the artificial lipid membrane, as shown in Figure 8.
  • the molecular size of Ara-C is l. llnm, which is larger than the van der Waals inner diameter (lnm) of the cyclic decapeptide c o Wyvyvy ⁇ Q].
  • the drug cannot mediate transmembrane transport via cyclic peptide nanotubes.
  • the results showed that cisplatin could not penetrate the bilayer membrane better without adding or adding a cyclic peptide.
  • Tumor cell line Human liver cancer BEL-74Q2 cell line.
  • the change in sensitivity to 5-FU after cyclic peptide nanotubes were applied to tumor cell membranes.
  • Experimental operation The tumor cell line was inoculated into a 96-well plate at 3000 cells/well. After 24 hours, a medium containing a certain concentration of CP and 5-FU was added for 48 hours, and the cytotoxicity of the drug was examined by MTT assay.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des compositions pharmaceutiques composées de nanotubes de peptide cyclique et des agents thérapeutiques et leurs utilisations. Les nanotubes sont assemblés par des peptides cycliques et leur diamètre intérieur de Van Der Waals est de 0,75 à 1,3 nm, tandis que la longueur des nanotubes est de 10 à 100 nm. Les peptides cycliques sont obtenus par cyclisation de 8, 10 ou 12 acides aminés. Le diamètre des agents thérapeutiques dans les compositions est inférieur au diamètre intérieur de Van Der Waals des nanotubes. Des canaux transmembranaires artificiels nanométriques peuvent être formés par les nanotubes et les agents thérapeutiques peuvent être transportés dans les cellules à travers les canaux par diffusion passive. Les compositions peuvent être utilisées pour traiter un cancer, une infection microbienne ou une infection virale.
PCT/CN2008/073015 2008-11-10 2008-11-11 Compositions pharmaceutiques comprenant des nanotubes de peptide cyclique et utilisations de celles-ci WO2010051667A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200810202475.3 2008-11-10
CN200810202475 2008-11-10

Publications (1)

Publication Number Publication Date
WO2010051667A1 true WO2010051667A1 (fr) 2010-05-14

Family

ID=42152457

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2008/073015 WO2010051667A1 (fr) 2008-11-10 2008-11-11 Compositions pharmaceutiques comprenant des nanotubes de peptide cyclique et utilisations de celles-ci

Country Status (1)

Country Link
WO (1) WO2010051667A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140145149A1 (en) * 2012-11-26 2014-05-29 Universal Display Corporation Organic Luminescent Compound With Delayed Fluorescence
CN114924003A (zh) * 2022-05-13 2022-08-19 河南省食品药品检验所 一种氟尿嘧啶口服乳中氟尿嘧啶含量的检测方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07233084A (ja) * 1994-02-24 1995-09-05 Takara Shuzo Co Ltd 化学療法剤効果増強剤
WO2002090503A2 (fr) * 2001-05-04 2002-11-14 The Scripps Research Institute Peptides antimicrobiens et compositions
WO2003093300A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Peptides anti-microbiens et compositions
WO2003092632A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Agents anticancereux de peptides cycliques et leurs procedes d'utilisation
WO2003092631A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Agents antiviraux de peptides cycliques et leurs procedes d'utilisation
CN1636590A (zh) * 1998-09-16 2005-07-13 默克专利股份公司 包含环肽和化学治疗剂或血管生成抑制剂的药用制剂

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07233084A (ja) * 1994-02-24 1995-09-05 Takara Shuzo Co Ltd 化学療法剤効果増強剤
CN1636590A (zh) * 1998-09-16 2005-07-13 默克专利股份公司 包含环肽和化学治疗剂或血管生成抑制剂的药用制剂
WO2002090503A2 (fr) * 2001-05-04 2002-11-14 The Scripps Research Institute Peptides antimicrobiens et compositions
WO2003093300A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Peptides anti-microbiens et compositions
WO2003092632A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Agents anticancereux de peptides cycliques et leurs procedes d'utilisation
WO2003092631A2 (fr) * 2002-05-06 2003-11-13 The Scripps Research Institute Agents antiviraux de peptides cycliques et leurs procedes d'utilisation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DARTOIS V. ET AL.: "Systemic Antibacterial Activity of Novel Synthetic Cyclic Peptides.", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY., vol. 49, no. 8, August 2005 (2005-08-01), pages 3302 - 3310 *
SARA FERNANDEZ-LOPEZ ET AL.: "Antibacterial agents based on the cyclic D,L-a-peptide architecture.", NATURE., vol. 412, 26 July 2001 (2001-07-26), pages 452 - 455 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140145149A1 (en) * 2012-11-26 2014-05-29 Universal Display Corporation Organic Luminescent Compound With Delayed Fluorescence
US9512136B2 (en) * 2012-11-26 2016-12-06 Universal Display Corporation Organic electroluminescent materials and devices
CN114924003A (zh) * 2022-05-13 2022-08-19 河南省食品药品检验所 一种氟尿嘧啶口服乳中氟尿嘧啶含量的检测方法
CN114924003B (zh) * 2022-05-13 2023-11-24 河南省食品药品检验所 一种氟尿嘧啶口服乳中氟尿嘧啶含量的检测方法

Similar Documents

Publication Publication Date Title
Das et al. Low molecular weight self-assembling peptide-based materials for cell culture, antimicrobial, anti-inflammatory, wound healing, anticancer, drug delivery, bioimaging and 3D bioprinting applications
Rodríguez-Vázquez et al. Recent advances in controlling the internal and external properties of self-assembling cyclic peptide nanotubes and dimers
Hamley Peptide nanotubes
Hamley Self-assembly of amphiphilic peptides
Gerbelli et al. Hierarchical Self‐Assembly of Peptides and its Applications in Bionanotechnology
Seabra et al. Biological applications of peptides nanotubes: An overview
Hsieh et al. Applications of cyclic peptide nanotubes (cPNTs)
KR20070004561A (ko) 분지형 펩티드 친양매성 화합물들, 그들의 관련된 에피토프화합물들 및 자가조립된 구조들
KR101325282B1 (ko) 베타-시트 폴리펩티드 블록 공중합체로 기능화된 생체활성 탄소나노튜브 복합체 및 그 제조방법
US8883967B2 (en) Branched amphipathic oligo-peptides that self-assemble into vesicles
Das et al. Ultrashort Peptides—A Glimpse into the Structural Modifications and Their Applications as Biomaterials
JPH08504837A (ja) 新規ポリペプチドおよびこれから調製される抗ｈｉｖ剤
KR101581926B1 (ko) 자기조립 펩타이드 나노캡슐 및 이를 포함하는 약물전달담체
CN106632695B (zh) 一种pH敏感性多肽及其应用
Goel et al. Fabrication of cationic nanostructures from short self-assembling amphiphilic mixed α/β-pentapeptide: Potential candidates for drug delivery, gene delivery, and antimicrobial applications
EP3405429B1 (fr) Formation de nanoparticules fonctionnalisées par co-assemblage supramoléculaire
Jeong et al. Macrocyclic peptides self-assemble into robust vesicles with molecular recognition capabilities
Xie et al. Recent progress in ionic coassembly of cationic peptides and anionic species
Arul et al. Fabrication of self-assembled nanostructures for intracellular drug delivery from diphenylalanine analogues with rigid or flexible chemical linkers
WO2018106273A1 (fr) Nanofibres et nanofeuilles ciblant le collagène
WO2010051667A1 (fr) Compositions pharmaceutiques comprenant des nanotubes de peptide cyclique et utilisations de celles-ci
US9018156B2 (en) Organic nanotube having hydrophobized inner surface, and encapsulated medicinal agent prepared using the nanotube
Ashwanikumar et al. Phenylalanine-containing self-assembling peptide nanofibrous hydrogel for the controlled release of 5-fluorouracil and leucovorin
CN111848731B (zh) 一种原位自组装的抗菌分子及其制备方法和应用
Bellotto et al. Nanotubes and water-channels from self-assembling dipeptides

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08877933

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08877933

Country of ref document: EP

Kind code of ref document: A1