CN115671408A - Substance capable of avoiding granulation tissue hyperplasia - Google Patents

Substance capable of avoiding granulation tissue hyperplasia Download PDF

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Publication number
CN115671408A
CN115671408A CN202211340164.XA CN202211340164A CN115671408A CN 115671408 A CN115671408 A CN 115671408A CN 202211340164 A CN202211340164 A CN 202211340164A CN 115671408 A CN115671408 A CN 115671408A
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China
Prior art keywords
copolymer
pouring
solution
hours
reaction
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Pending
Application number
CN202211340164.XA
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Chinese (zh)
Inventor
沈佳伟
杨乐
唐玉爽
刘国兴
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Jinfu Beijing Medical Technology Co ltd
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Jinfu Beijing Medical Technology Co ltd
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.)
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Application filed by Jinfu Beijing Medical Technology Co ltd filed Critical Jinfu Beijing Medical Technology Co ltd
Priority to CN202211340164.XA priority Critical patent/CN115671408A/en
Publication of CN115671408A publication Critical patent/CN115671408A/en
Pending legal-status Critical Current

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Abstract

The invention discloses a substance capable of avoiding granulation tissue hyperplasia, which comprises spraying medicine and copolymer with the weight ratio of 3:1, wherein the spraying is carried out by a spraying device, and the speed in the spraying process is 1 ml/min. The invention can effectively inhibit granulation hyperplasia, has strong practicability and functionality, and can be widely applied to the technical field of trachea valve and stent implantation.

Description

Substance capable of avoiding granulation tissue hyperplasia
Technical Field
The invention relates to the technical field of trachea valve and stent implantation, in particular to a substance capable of avoiding granulation tissue hyperplasia.
Background
The stenosis of the trachea and the bronchus caused by various reasons can cause various clinical symptoms such as obstructive pulmonary inflammation, atelectasis, dyspnea and the like, and serious patients can have respiratory failure and are life threatening. Surgical treatment is usually adopted for the patients in the past, and the treatment is difficult, the wound is large, and the risk is high. In recent years, with the development of endoscope technology, biocompatible materials and stent fabrication technology, the airway flap and stent implantation technology is mature and attracts more and more attention. Through valve and bracket implantation, most patients with narrow air passages and slow obstruction of the lung can benefit, and symptoms can be quickly relieved. Therefore, valve and stent implantation become one of the important means for treating airway stenosis and chronic obstructive pulmonary disease.
However, the implantation of the valve and the stent in the air passage has the problem of stimulating granulation tissue proliferation to cause the restenosis of the tube cavity, which is a great problem influencing the clinical curative effect after the valve and the stent are implanted. Therefore, a technique capable of solving this problem is yet to be proposed.
Disclosure of Invention
In order to solve the problems, the invention provides a medicament capable of effectively preventing the granulation hyperplasia.
The technical scheme provided by the invention is as follows:
a substance capable of preventing granulation tissue proliferation comprises a spray coating agent and a copolymer in a weight ratio of 3:1, which is sprayed by a spray coating device at a speed of 1 ml/min during the spraying process.
Preferably, the copolymer comprises the following preparation steps:
1) Synthesis of benzyl bromoacetyl aspartate:
taking a 500ml flask, connecting nitrogen by a tee joint, vacuumizing, and filling nitrogen for three times;
dripping 4ml of NaoH into the bottle at constant pressure;
controlling the number of drops, and measuring the number to be 8-9 by using a PH test paper;
the reaction process is carried out in a stirrer, and the whole process is controlled within 30-40 minutes;
adding 35ml of concentrated hydrochloric acid, and adjusting the pH value to 2.0;
adding 100ml of saturated saline, fully shaking up, pouring the lower waste liquid, and adding 100ml of saturated saline for five times;
distilling to obtain lower layer liquid;
2) Catalyst preparation:
adding 100ml of dichloromethane and 10g of calcium chloride into a distillation flask;
adding stannous octoate;
putting into a drying box;
extracting the two liquids by using a syringe, adding the two liquids in a certain amount, shaking the two liquids uniformly, and adding the mixture to 50ml to obtain 10g of dichloromethane to calcium chloride, wherein the ratio of the dichloromethane to the calcium chloride is 100ml;
3) Polymerization to give a copolymer:
2g of morpholine dione benzyl ester, 10g of L-lactide, 1.5ml of catalyst, reaction temperature of 150-155 ℃ and 6 hours;
putting the L-lactide in a drying box, and vacuumizing the drying box;
pouring 20g L-propyl lactide into a reaction bottle;
4g of morpholine dione benzyl ester is added into a reaction bottle;
adding the prepared catalyst solution, and sealing the reaction bottle;
fixing the reaction bottle in a 155-DEG oil bath pot and stirring for 6 hours;
crushing the reaction bottle, and taking out the solid;
putting the solid into a 600ml measuring cup, adding 300ml of dichloromethane, and stirring on a stirrer until the dichloromethane is completely dissolved;
filtering with a second filter;
adding a stirrer into a 1000ml beaker, and slowly adding 800ml of methanol into the filtered liquid to obtain a cotton-like substance;
using toilet paper to suck the methanol;
putting the plate filled with the copolymer into a 50-DEG vacuum drying oven by using a preservative film to dry for 4-12 hours;
putting the dried copolymer in a dryer for later use;
4) Degreasing protection of the copolymer:
10g of the copolymer was placed in a 1000ml spherical reaction flask;
adding 400ml of tetrahydrofuran, and stirring until the tetrahydrofuran is dissolved;
adding 3.5g of palladium-carbon hydrogenation catalyst and fully shaking 100ml of anhydrous methanol;
pouring the solution after shaking into tetrahydrofuran solution;
after reacting for 3 hours, pouring the solution into a No. 4 filter for filtering;
pouring the liquid into a centrifuge tube for centrifugation, carrying out 13000 revolutions for 10 minutes;
pouring the centrifuged liquid into petroleum ether to obtain a polymer;
drying in a drying oven for 6 hours in vacuum;
5) Heparinizing:
dissolving 1.6g heparin sodium in 53ml water and 0.1m HCL 10ml water;
slowly pouring the dissolved heparin sodium solution into a reaction bottle and stirring;
placing the reaction bottle in ice water with the temperature of 4 ℃ and stirring for reaction for 24 hours;
pouring petroleum ether into a 600ml beaker, adding a stirrer, and slowly adding the solution to precipitate to obtain a precipitate;
dissolving the copolymer in tetrahydrofuran;
centrifuging for 10 minutes by using a centrifuge;
precipitating the solution in petroleum ether to obtain a copolymer;
the copolymer was dried at room temperature for 24 hours.
Preferably, the spraying medicine is tranilast with the specification of 50-200mg/kg.
Compared with the prior art, the invention has the advantages that:
by adopting the technical scheme provided by the invention, the effect of effectively preventing the granulation hyperplasia is achieved, and the curative effect is good
Detailed Description
The present invention will be described in further detail with reference to examples.
A substance capable of preventing granulation tissue proliferation comprises a spray coating agent and a copolymer in a weight ratio of 3:1, which is sprayed by a spray coating device at a speed of 1 ml/min during the spraying process.
The copolymer comprises the following preparation steps:
1) Synthesis of benzyl bromoacetyl aspartate:
taking a 500ml flask, connecting nitrogen by a tee joint, vacuumizing, and filling nitrogen for three times;
dripping 4ml of NaoH into the bottle at constant pressure;
controlling the number of drops, and measuring the number to be 8-9 by using a PH test paper;
the reaction process is carried out in a stirrer, and the whole process is controlled within 30-40 minutes;
adding 35ml of concentrated hydrochloric acid, and adjusting the pH value to 2.0;
adding 100ml of saturated saline, fully shaking up, pouring the lower waste liquid, and adding 100ml of saturated saline for five times;
distilling to obtain lower layer liquid;
2) Catalyst preparation:
adding 100ml of dichloromethane and 10g of calcium chloride into a distillation flask;
adding stannous octoate;
putting the mixture into a drying box;
extracting the two liquids by using a syringe, adding the two liquids in a certain amount, shaking the two liquids uniformly, and adding the mixture to 50ml to obtain 10g of dichloromethane to calcium chloride, wherein the ratio of the dichloromethane to the calcium chloride is 100ml;
3) Polymerization to give a copolymer:
2g of morpholine dione benzyl ester, 10g of L-lactide, 1.5ml of catalyst, reaction temperature of 150-155 ℃ and 6 hours;
putting the L-lactide in a drying box, and vacuumizing the drying box;
pouring 20g L-propyl lactide into a reaction bottle;
4g of morpholine dione benzyl ester is added into a reaction bottle;
adding the prepared catalyst solution, and sealing the reaction bottle;
fixing the reaction bottle in a 155-DEG oil bath pot and stirring for 6 hours;
crushing the reaction bottle, and taking out the solid;
putting the solid into a 600ml measuring cup, adding 300ml of dichloromethane, and stirring on a stirrer until the solid is completely dissolved;
filtering with a second filter;
adding a stirrer into a 1000ml beaker, and slowly adding 800ml of methanol into the filtered liquid to obtain a cotton-like substance;
using toilet paper to suck the methanol;
putting the plate filled with the copolymer into a 50-DEG vacuum drying oven by using a preservative film to dry for 4-12 hours;
putting the dried copolymer in a dryer for standby;
4) Degreasing protection of the copolymer:
10g of the copolymer was placed in a 1000ml spherical reaction flask;
adding 400ml of tetrahydrofuran, and stirring until the tetrahydrofuran is dissolved;
adding 3.5g of palladium-carbon hydrogenation catalyst and 100ml of anhydrous methanol, and fully shaking up;
pouring the uniformly shaken solution into a tetrahydrofuran solution;
after reacting for 3 hours, pouring the solution into a No. 4 filter for filtering;
pouring the liquid into a centrifuge tube for centrifugation, carrying out 13000 revolutions for 10 minutes;
pouring the centrifuged liquid into petroleum ether to obtain a polymer;
drying in a drying oven for 6 hr;
5) Heparinizing:
dissolving 1.6g heparin sodium in 53ml of water and 10ml of 0.1m HCL;
slowly pouring the dissolved heparin sodium solution into a reaction bottle and stirring;
placing the reaction bottle in ice water with the temperature of 4 ℃ and stirring for reaction for 24 hours;
pouring petroleum ether into a 600ml beaker, adding a stirrer, and slowly adding the solution to precipitate to obtain a precipitate;
dissolving the copolymer in tetrahydrofuran;
centrifuging for 10 minutes by using a centrifuge;
precipitating the solution in petroleum ether to obtain a copolymer;
the copolymer was dried at room temperature for 24 hours.
The spray coating medicine is tranilast with a specification of 50-200mg/kg.
In the implementation process of the technical scheme provided by the invention, the effect of avoiding granulation tissue proliferation can be achieved, and the operability is strong.
Moreover, the invention is applied to the specific clinical experiment process, achieves more obvious technical effect, simplifies the medical operation of medical care personnel in the implementation process, and has accurate operation.
Other adjustments to the stirring process, the reaction temperature during the preparation of the copolymer, and the time of drying the copolymer plate in the drying oven as set forth in the present invention are within the scope of the present application.

Claims (3)

1. A substance capable of preventing granulation tissue proliferation, comprising a spray drug and a copolymer in a weight ratio of 3:1, which is sprayed by a spray device at a speed of 1 ml/min during spraying.
2. The substance capable of avoiding the proliferation of granulation tissue as claimed in claim 1, wherein said copolymer comprises the following preparation steps:
1) Synthesis of benzyl bromoacetyl aspartate:
taking a 500ml flask, connecting nitrogen by a tee joint, vacuumizing, and filling nitrogen for three times;
dripping 4ml of NaoH into the bottle at constant pressure;
controlling the number of drops, and measuring the number to be 8-9 by using a PH test paper;
the reaction process is carried out in a stirrer, and the whole process is controlled to be 30-40 minutes;
adding 35ml of concentrated hydrochloric acid, and adjusting the pH value to 2.0;
adding 100ml of saturated saline, fully shaking up, pouring the lower waste liquid, and adding 100ml of saturated saline for five times;
distilling to obtain lower layer liquid;
2) Catalyst preparation:
adding 100ml of dichloromethane and 10g of calcium chloride into a distillation flask;
adding stannous octoate;
putting the mixture into a drying box;
extracting the two liquids by using a syringe, adding the two liquids in a certain amount, shaking the two liquids uniformly, and adding the mixture to 50ml to obtain 10g of dichloromethane to calcium chloride, wherein the ratio of the dichloromethane to the calcium chloride is 100ml;
3) Polymerization to give a copolymer:
2g of morpholine dione benzyl ester, 10g of L-lactide, 1.5ml of catalyst, reaction temperature of 150-155 ℃ and 6 hours;
putting the L-lactide in a drying box, and vacuumizing the drying box;
pouring 20g L-propyl lactide into a reaction bottle;
4g of morpholine dione benzyl ester is added into a reaction bottle;
adding the prepared catalyst solution, and sealing the reaction bottle;
fixing the reaction bottle in a 155-DEG oil bath pot and stirring for 6 hours;
crushing the reaction bottle, and taking out the solid;
putting the solid into a 600ml measuring cup, adding 300ml of dichloromethane, and stirring on a stirrer until the dichloromethane is completely dissolved;
filtering with a second filter;
adding a stirrer into a 1000ml beaker, and slowly adding 800ml of methanol into the filtered liquid to obtain a cotton-like substance;
using toilet paper to suck the methanol;
putting the plate filled with the copolymer into a 50-DEG vacuum drying oven by using a preservative film to dry for 4-12 hours;
putting the dried copolymer in a dryer for later use;
4) Degreasing protection of the copolymer:
10g of the copolymer was placed in a 1000ml spherical reaction flask;
adding 400ml of tetrahydrofuran, and stirring until the tetrahydrofuran is dissolved;
adding 3.5g of palladium-carbon hydrogenation catalyst and 100ml of anhydrous methanol, and fully shaking up;
pouring the solution after shaking into tetrahydrofuran solution;
after reacting for 3 hours, pouring the solution into a No. 4 filter for filtering;
pouring the liquid into a centrifuge tube for centrifugation, carrying out 13000 revolutions for 10 minutes;
pouring the centrifuged liquid into petroleum ether to obtain a polymer;
drying in a drying oven for 6 hr;
5) Heparinizing:
dissolving 1.6g heparin sodium in 53ml water and 0.1m HCL 10ml water;
slowly pouring the dissolved heparin sodium solution into a reaction bottle and stirring;
placing the reaction bottle in ice water with the temperature of 4 ℃ and stirring for reaction for 24 hours;
pouring petroleum ether into a 600ml beaker, adding a stirrer, and slowly adding the solution to precipitate to obtain a precipitate;
dissolving the copolymer in tetrahydrofuran;
centrifuging for 10 minutes by using a centrifuge;
precipitating the solution in petroleum ether to obtain a copolymer;
the copolymer was dried at room temperature for 24 hours.
3. The dosing method capable of preventing granulation tissue proliferation as claimed in claim 2, wherein the spraying medicine is tranilast with a specification of 50-200mg/kg.
CN202211340164.XA 2022-10-29 2022-10-29 Substance capable of avoiding granulation tissue hyperplasia Pending CN115671408A (en)

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CN202211340164.XA CN115671408A (en) 2022-10-29 2022-10-29 Substance capable of avoiding granulation tissue hyperplasia

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211340164.XA CN115671408A (en) 2022-10-29 2022-10-29 Substance capable of avoiding granulation tissue hyperplasia

Publications (1)

Publication Number Publication Date
CN115671408A true CN115671408A (en) 2023-02-03

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1418641A (en) * 2001-11-12 2003-05-21 华东理工大学 Polyester with its main train having amino acid and contg. active drug, and its prepn. method
US20030108588A1 (en) * 2001-09-17 2003-06-12 Jianbing Chen Stent coated with a sustained-release drug delivery and method for use thereof
AU2004325203A1 (en) * 2004-11-24 2006-06-01 Seo Hong Yoo Dried forms of aqueous solubilized bile acid dosage formulation: preparation and uses thereof
CN101181650A (en) * 2006-08-02 2008-05-21 上海市普陀区中心医院 Bracket for controlling releasing and elution of tranilast medicament coating
US20100074934A1 (en) * 2006-12-13 2010-03-25 Hunter William L Medical implants with a combination of compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030108588A1 (en) * 2001-09-17 2003-06-12 Jianbing Chen Stent coated with a sustained-release drug delivery and method for use thereof
CN1418641A (en) * 2001-11-12 2003-05-21 华东理工大学 Polyester with its main train having amino acid and contg. active drug, and its prepn. method
AU2004325203A1 (en) * 2004-11-24 2006-06-01 Seo Hong Yoo Dried forms of aqueous solubilized bile acid dosage formulation: preparation and uses thereof
CN101181650A (en) * 2006-08-02 2008-05-21 上海市普陀区中心医院 Bracket for controlling releasing and elution of tranilast medicament coating
US20100074934A1 (en) * 2006-12-13 2010-03-25 Hunter William L Medical implants with a combination of compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
张晓飞: "《吗啉-2, 5-二酮衍生物的合成及其与丙交酯的共聚研究》", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》, no. 10, pages 014 - 122 *
赵燕超等: "《肝素化吗林二酮衍生物与L-丙交酯共聚物制备与表征》", 《2005年全国高分子学术论文报告会》, pages 638 - 125 *

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