A redox-sensitive curcumin prodrug micelle, micelle monomer and preparation method thereof

Abstract

The invention relates to curcumin prodrug micelle with oxidation and reduction sensitivity, a micellar monomer and a preparation method of the micellar monomer. The invention aims at providing a synthesis design method of the curcumin prodrug micelle with oxidation and reduction sensitivity. A molecular formula of the curcumin prodrug micelle monomer is as follows: MPEG-PLA-SS-Cur. According to the preparation method of the curcumin prodrug micelle monomer, raw materials for reaction comprise (methoxyl poly(ethylene glycol)-polylactic acid (MPEG-PLA), and curcumin Cur-SS-COOH modified by dithiodipropionic acid. The curcumin prodrug micelle with oxidation and reduction sensitivity, the micellar monomer and the preparation method provided by the invention have the following advantages that the micellar monomer product obtained by the preparation method has reduction responsiveness on the curcumin prodrug micelle, breaks through a conventional drug administration mode of encapsulating a drug by using a carrier, i.e., the drug is a part of the carrier; by controlling the use of inert carrier materials, the drug loading capacity, particle size and stability of a micellar system are improved significantly, and the EPR (Ethylene Propylene Rubber) effect is enhanced.

Description

Technical field:

[0001] The invention relates to a pharmaceutical preparation characterized by a special physical shape, and further relates to a redox-sensitive curcumin prodrug micelle, a micelle monomer and a preparation method thereof. Background technique:

[0002] As we all know, cancer has become one of the most important diseases that threaten human life and health. At present, the clinical treatment of cancer mainly includes radiation therapy, surgical resection, and drug chemotherapy. Among them, drug chemotherapy is the most widely used in cancer treatment, but there are many deficiencies in traditional drug delivery methods: anticancer drugs not only kill cancer cells in the human body, but also kill normal cells in the human body effect, resulting in toxic side effects. In addition, the half-life of anticancer drugs in the body is short, and the concentration in the tumor site is insufficient. Therefore, in order to achieve the therapeutic dose, the dosage mus...

Examples

Embodiment 1-1

[0043] Example 1-1: Take 10g of MPEG2000 and place it in a 250mL round bottom flask, stir and melt in an oil bath at 60°C, then add 10g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess ice ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Embodiment 1-2

[0044] Example 1-2: Take 10g of MPEG2000 and place it in a 250mL round bottom flask, stir and melt in an oil bath at 60°C, then add 8g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess ice ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Embodiment 1-3

[0045] Example 1-3: Take 10g of MPEG2000 and place it in a 250mL round-bottomed flask, stir and melt in an oil bath at 60°C, then add 5g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess glacial ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Technical field:

[0001] The invention relates to a pharmaceutical preparation characterized by a special physical shape, and further relates to a redox-sensitive curcumin prodrug micelle, a micelle monomer and a preparation method thereof. Background technique:

[0002] As we all know, cancer has become one of the most important diseases that threaten human life and health. At present, the clinical treatment of cancer mainly includes radiation therapy, surgical resection, and drug chemotherapy. Among them, drug chemotherapy is the most widely used in cancer treatment, but there are many deficiencies in traditional drug delivery methods: anticancer drugs not only kill cancer cells in the human body, but also kill normal cells in the human body effect, resulting in toxic side effects. In addition, the half-life of anticancer drugs in the body is short, and the concentration in the tumor site is insufficient. Therefore, in order to achieve the therapeutic dose, the dosage mus...

Examples

Embodiment 1-1

[0043] Example 1-1: Take 10g of MPEG2000 and place it in a 250mL round bottom flask, stir and melt in an oil bath at 60°C, then add 10g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess ice ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Embodiment 1-2

[0044] Example 1-2: Take 10g of MPEG2000 and place it in a 250mL round bottom flask, stir and melt in an oil bath at 60°C, then add 8g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess ice ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Embodiment 1-3

[0045] Example 1-3: Take 10g of MPEG2000 and place it in a 250mL round-bottomed flask, stir and melt in an oil bath at 60°C, then add 5g of lactide, heat up to 100°C until completely melted, vacuumize, protect with nitrogen, and add lactide The mass of 0.2% stannous octoate was heated to 125°C, and melted and polymerized for 24 hours. After the reaction is finished, wait for the system to cool down to room temperature, dissolve with an appropriate amount of tetrahydrofuran (using ultrasound), remove part of the solvent by rotary evaporation, drop into excess glacial ether to precipitate, repeat three times, and filter with suction to obtain a white flocculent solid, which is dissolved in 15mL of tetrahydrofuran , put it into a dialysis bag with a molecular weight cut-off of 3500, and then put it into 1000mL distilled water for dialysis for 24 hours. Hour.

Images