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Preparation method and application of oligopeptide hydrogel, and medicinal composition

A technology of hydrogel and composition, applied in the preparation method and application of short peptide hydrogel, and the field of pharmaceutical composition, can solve the problems of lack of selectivity of tumor tissue, affecting the ability of action, strong side effects and the like

Active Publication Date: 2018-11-23
NANKAI UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, chemotherapy is mainly based on some chemotherapy drugs, such as chlorambucil, paclitaxel, camptothecin and doxorubicin, etc., they mainly kill tumor cells by inducing apoptosis and inhibiting cell growth, but the side effects are very serious. powerful
Radiation therapy mainly uses some electron rays with different energies to continuously irradiate malignant tumors to kill cancer cells or inhibit the growth and spread of cancer cells. However, it lacks selectivity for tumor tissues and damages normal tissues. can not be ignored
Surgical treatment has strong limitations, not all cancer patients can be treated by surgical resection
At the same time, surgical resection is accompanied by sequelae, which may affect mobility and respiratory failure.

Method used

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  • Preparation method and application of oligopeptide hydrogel, and medicinal composition
  • Preparation method and application of oligopeptide hydrogel, and medicinal composition
  • Preparation method and application of oligopeptide hydrogel, and medicinal composition

Examples

Experimental program
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Effect test

preparation Embodiment 1

[0065] Preparation of Anti-tumor Short Peptide and Antibody Co-Assembly

[0066] (1) Synthesis of D-configuration short peptide CRB-HA-G by Fmoc-solid-phase synthesis method D f D Fp D Y, the structural formula is as follows:

[0067]

[0068] Specific steps are as follows:

[0069] 1) Swelling: Weigh 1mmol of 2-Cl-Trt resin in a solid-phase synthesizer, then add 15mL of dichloromethane (hereinafter referred to as DCM), place on a shaker and shake for 15min, so that the 2-Cl-Trt resin is fully swelling;

[0070] 2) Remove the DCM from the solid-phase synthesizer equipped with 2-Cl-Trt resin with an ear cleaning ball;

[0071] 3) Dissolve 1.5mmol of Fmoc-protected amino acid in 10mL of anhydrous DCM, add 3mmol of DIEPA, transfer to the above-mentioned solid-phase synthesizer after fully dissolved, and react at room temperature for 1.5h;

[0072] 4) Sealing: Remove the reaction solution in the solid-phase synthesizer with ear wash ball, then wash with 10mL of anhydrous ...

preparation Embodiment 2

[0082] Preparation of Cy5.5 Short Peptide and Antibody Co-Assembly

[0083] (1) Synthesis of D-configuration short peptide Cy5.5-G by Fmoc-solid-phase synthesis method D f D Fp D Y, the structural formula is as follows:

[0084]

[0085] The specific steps are as described in Preparation Example 1, and the end-capping group is Cy5.5.

[0086] Its structural characterization data are as follows:

[0087] 1 H NMR (400MHz,DMSO)δ11.32(s,1H),9.19(s,1H),8.56–8.30(m,2H),8.20–7.96(m,3H),7.86(d,J=8.3Hz, 1H), 7.51–7.30(m, 3H), 7.26–7.01(m, 11H), 6.89(t, J=6.3Hz, 2H), 6.65(d, J=8.3Hz, 2H), 4.62–4.35(m ,3H),3.83–3.41(m,4H),2.98(dd,J=9.7,4.0Hz,1H),2.78–2.56(m,3H),2.33(t,J=11.5Hz,1H),1.35( d,J=5.8Hz,3H).

[0088] (2) Take 1mg Cy5.5-G D f D Fp D Y is placed in a 4mL glass bottle, add 0.2mg or 0.3mg of antibody, and then add PBS solution (pH=7.4) to make up to a total volume of 1mL, and adjust its pH value to 7.4 with 1M sodium carbonate solution , mix well and sonicate at room...

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Abstract

The invention provides a preparation method and application of oligopeptide hydrogel, and a medicinal composition. The obtained oligopeptide hydrogel has a good targeting tumor suppression effect or in-vivo imaging effect. The preparation method of the oligopeptide hydrogel includes the steps of mixing oligopeptide with an antibody in a water solution, and assembling the oligopeptide and the antibody into the hydrogel under the enzymatic action at the temperature of 2-6 DEG C, wherein the oligopeptide can form the hydrogel under the enzymatic action, and the antibody has a targeting effect ontumor cells. The capping groups of the oligopeptide are groups having an antitumor effect or in-vivo imaging effect; preferably, the antitumor groups are chlorambucil, and the groups with the in-vivoimaging effect are Cy5.5; more preferably, the sequence of the oligopeptide is X-GDFDFpDY, and the X is chlorambucil or Cy5.5; preferably, the antibody is antiHER2.

Description

technical field [0001] The invention relates to a preparation method, application and pharmaceutical composition of a short peptide hydrogel. Background technique [0002] The occurrence and development of cancer pose a serious threat to human health and social and economic development, and the number of people who die from cancer worldwide is increasing at an alarming rate every year. The World Cancer Report shows that the incidence of cancer worldwide is increasing rapidly. The number of cancer patients in the world will increase from 14 million in 2012 to 19 million in 2035, and will reach 24 million by 2050. Therefore, it has become urgent to continuously explore and develop more powerful cancer treatment methods to curb the huge threat of tumors to human health as soon as possible. [0003] Traditionally, there are three main types of cancer treatment: chemotherapy, radiotherapy, and surgical resection. Among them, chemotherapy is mainly based on some chemotherapy dr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/68A61K47/65A61K31/196A61K49/00A61P35/00
CPCA61K31/196A61K49/0034A61K49/0058A61K49/0073A61K47/65A61K47/68A61K47/6903A61P35/00
Inventor 杨志谋梁春惠王玲
Owner NANKAI UNIV
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