CN109731131B - Antibacterial dressing for skin cancer chemotherapy and preparation method thereof - Google Patents
Antibacterial dressing for skin cancer chemotherapy and preparation method thereof Download PDFInfo
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- CN109731131B CN109731131B CN201811578854.2A CN201811578854A CN109731131B CN 109731131 B CN109731131 B CN 109731131B CN 201811578854 A CN201811578854 A CN 201811578854A CN 109731131 B CN109731131 B CN 109731131B
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- 208000000453 Skin Neoplasms Diseases 0.000 title claims abstract 16
- 201000000849 skin cancer Diseases 0.000 title claims abstract 16
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract 14
- 238000002512 chemotherapy Methods 0.000 title claims abstract 13
- 238000002360 preparation method Methods 0.000 title claims abstract 5
- 239000003814 drug Substances 0.000 claims abstract 11
- 229940079593 drug Drugs 0.000 claims abstract 11
- 229920001992 poloxamer 407 Polymers 0.000 claims abstract 8
- 108010020346 Polyglutamic Acid Proteins 0.000 claims abstract 7
- 229920002643 polyglutamic acid Polymers 0.000 claims abstract 7
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims abstract 6
- 239000000693 micelle Substances 0.000 claims abstract 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 6
- 238000003756 stirring Methods 0.000 claims abstract 5
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 claims abstract 2
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 claims abstract 2
- 238000002156 mixing Methods 0.000 claims abstract 2
- 229960003732 tyramine Drugs 0.000 claims abstract 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims 5
- 239000000243 solution Substances 0.000 claims 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- 239000002245 particle Substances 0.000 claims 3
- 239000011550 stock solution Substances 0.000 claims 3
- 238000004108 freeze drying Methods 0.000 claims 2
- 239000012528 membrane Substances 0.000 claims 2
- 239000011259 mixed solution Substances 0.000 claims 2
- NLTQZUCBHQFOIO-UHFFFAOYSA-N acetohydrazide;trimethylazanium;chloride Chemical compound [Cl-].C[NH+](C)C.CC(=O)NN NLTQZUCBHQFOIO-UHFFFAOYSA-N 0.000 claims 1
- 238000005576 amination reaction Methods 0.000 claims 1
- 230000000845 anti-microbial effect Effects 0.000 claims 1
- 230000000973 chemotherapeutic effect Effects 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 238000002390 rotary evaporation Methods 0.000 claims 1
- 238000009210 therapy by ultrasound Methods 0.000 claims 1
- -1 1-ethyl- (3-dimethylaminopropyl) Chemical group 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 abstract 1
- 206010048038 Wound infection Diseases 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 230000008595 infiltration Effects 0.000 abstract 1
- 238000001764 infiltration Methods 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
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Abstract
The invention discloses a dressing for antibacterial skin cancer chemotherapy and a preparation method thereof, wherein the preparation method comprises the following steps: (1) dissolving the Pluronic F127 drug-loaded micelle modified by amino in water to prepare a solution with the concentration of 2-6 wt%, and uniformly stirring; (2) dissolving quaternized polyglutamic acid in water, adding tyramine hydrochloride, and preparing a polyglutamic acid solution with the concentration of 15-20 wt%; (3) and (2) uniformly mixing the solutions obtained in the steps (1) and (2), adding 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride and N-hydroxysuccinimide, stirring, pouring the solution into a mold, and demolding after 2-5 min to obtain the dressing for the antibacterial skin cancer chemotherapy. The dressing for the antibacterial skin cancer chemotherapy, which is prepared by the method disclosed by the invention, has an ideal uniform network structure, is high in self-healing efficiency, has broad-spectrum antibacterial property, prevents wound infection, can be used for repairing wounds after skin cancer physical excision operation, inhibits infiltration tumor tissues which cannot be excised, and prevents relapse.
Description
Technical Field
The invention belongs to the technical field of preparation of biomedical materials, and particularly relates to a dressing for antibacterial skin cancer chemotherapy and a preparation method thereof.
Background
The population of skin cancer patients has increased in recent years, about 500 million people are diagnosed with skin cancer worldwide each year, 1 skin cancer patient per 5 people in the united states, and the prevalence rates have increased year by year. Tumors located on the superficial surface of the skin are usually treated by surgical resection, but in case of invasive tumors, the tumors are often difficult to resect and easy to recur after the operation, thereby causing treatment failure. Moreover, the gap-type operation wound is easy to infect in the repair process, and scar tissues are drawn too tightly after healing, so that the appearance of a patient is affected.
The hydrogel is a gel material taking water as a dispersion medium, is formed by crosslinking one or more hydrophilic macromolecules under the action of covalent bonds or non-covalent bonds, has an excellent three-dimensional network structure, and has a stable spatial three-dimensional structure so that the hydrogel retains water and does not have structural change, and therefore, the hydrogel is widely applied to skin repair dressings due to good permeability and biocompatibility. However, simple hydrogels generally do not have excellent antimicrobial properties over a broad spectrum, and their antimicrobial properties are often improved by adding antimicrobial agents. Despite its excellent antibacterial properties, nano-silver has been prohibited by FDA for use in medical products due to its instability and cytotoxicity. Polymeric antimicrobial agents have recently emerged in which antimicrobial groups are grafted onto polymeric carriers. The antibacterial groups are concentrated on the surface of the carrier, so that the concentration is increased, the sterilization time is shortened, and the sterilization effect is improved. In addition, the polymer quaternary ammonium salt antibacterial agent has the advantages of remarkable antibacterial effect, good heat resistance, low toxicity and the like, so the polymer quaternary ammonium salt antibacterial agent becomes a hotspot of research in the field of antibacterial agents.
Meanwhile, the hydrogel is used as an excellent drug carrier and has a drug slow-release effect in the treatment process, but the drug release speed is high in a mode of physically mixing and loading the drug, so that the aims of controlling the drug concentration and performing long-acting treatment are difficult to achieve. And most of the drugs clinically used for treating skin cancer are fat-soluble and can not be continuously dispersed in a hydrogel matrix.
At present, no report of the polyglutamic acid-based dressing with broad-spectrum antibacterial property, good continuous dispersibility and slow-release effect for the postoperative chemotherapy of skin cancer is published at home and abroad, so how to prepare the polyglutamic acid-based dressing for the postoperative chemotherapy of skin cancer is an urgent problem to be solved.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the dressing for the antibacterial skin cancer chemotherapy and the preparation method thereof, the amino-modified Pluronic F127 micelle is crosslinked in a hydrogel network and used as a carrier of a clinical skin cancer fat-soluble chemotherapy drug, responds to the acidic environment of tumor tissues, releases for a long time, can effectively solve the hidden trouble of relapse of the anti-cancer drug after skin cancer physical excision surgery, and the quaternary ammonium salt and tyramine hydrochloride modified polyglutamic acid-based gel can effectively inhibit the inflammation of wounds, enhance the adhesive force between the dressing and the wounds and promote the healing of the wounds.
In order to achieve the purpose, the technical scheme adopted by the invention for solving the technical problems is as follows:
a preparation method of the dressing for the antibacterial skin cancer chemotherapy comprises the following steps:
(1) dissolving the amino-modified Pluronic F127 drug-loaded micelle particles in water to prepare an amino-modified Pluronic F127 drug-loaded micelle solution with the concentration of 2-6 wt%;
(2) dissolving 3-5 parts by mass of quaternized polyglutamic acid in water, adding 1 part by mass of tyramine hydrochloride, and preparing a polyglutamic acid solution with the concentration of 15-20 wt%;
(3) uniformly mixing the solutions obtained in the step (1) and the step (2) according to the volume ratio of 1:2 to obtain a mixed solution;
(4) adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide into the mixed solution obtained in the step (3), and stirring for 1-3 min to obtain dressing stock solution for the antibacterial skin cancer chemotherapy; in the dressing stock solution for the antibacterial skin cancer chemotherapy, the content of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride is 20-33.33 mg/ml, and the content of N-hydroxysuccinimide is 10-16.67 mg/ml;
(5) finally, pouring the dressing stock solution for the antibacterial skin cancer chemotherapy obtained in the step (4) into a mold, standing for 2-5 min for coagulation, and demolding to obtain the dressing for the antibacterial skin cancer chemotherapy, wherein the mold is preferably a tetrafluoroethylene mold;
the water is preferably physiological saline.
Further, the preparation method of the amino-modified Pluronic F127 drug-loaded micelle particle in the step (1) is as follows: 0.1 to 0.3 mass part of amino modified Pluronic F127 and 0.01 to 0.03 mass part of anti-skin cancer liposoluble medicine are dissolved in 3.95 to 11.85 mass parts of acetonitrile solution at 25 to 40 ℃ and 0.06 to E
Rotationally evaporating under 0.08MPa for 30min to form a medicine film, placing the medicine film at 40-60 ℃ to form a gel state, adding 5-15 parts by mass of water at the same temperature for hydration treatment, uniformly stirring, performing ultrasonic treatment for 10-20 min to obtain an amino-modified Pluronic F127 drug-loaded micelle solution, and performing freeze drying to obtain white powder, namely amino-modified Pluronic F127 drug-loaded micelle particles, wherein the water is preferably normal saline.
Further, amino modified Pluronic F127 was modified by terminal amination.
Further, the preparation method of the quaternized polyglutamic acid in the step (2) is as follows: dissolving 1.47 parts by mass of polyglutamic acid and 0.1-0.3 part by mass of quaternary ammonium salt micromolecule in water to prepare a solution with the weight percent of 10-15, adding 0.12-0.36 part by mass of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, uniformly stirring, adding 0.06-0.18 part by mass of N-hydroxysuccinimide after 5-10 min, reacting for 20-30 min, dialyzing to remove the 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and the N-hydroxysuccinimide, and freeze-drying to obtain white floccule, namely quaternized polyglutamic acid, wherein the water is preferably physiological saline.
Further, the quaternary ammonium salt micromolecule is acethydrazide trimethyl ammonium chloride.
Further, the mass ratio of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride to N-hydroxysuccinimide added in the step (4) and the step of preparing the quaternized polyglutamic acid is 2: 1.
The invention also relates to the dressing for the antibacterial skin cancer chemotherapy, which is prepared by the preparation method.
The invention has the beneficial effects that:
1. the polyglutamic acid-based hydrogel has an ideal uniform network structure and a straight-chain molecular configuration, so that the polyglutamic acid-based hydrogel has excellent toughness, and can be used as a skin dressing to prevent the dressing from being torn and exposing wounds in the repair period of a patient and influencing the recovery effect. Through quaternization modification, the antibacterial wound dressing has broad-spectrum antibacterial property, is easy to obtain materials, has stable physical and chemical properties, can effectively inhibit wound infection, and improves wound recovery efficiency.
2. The gel network has reversible dynamic chemical groups due to the addition of tyramine hydrochloride, so that the gel has good self-healing efficiency, and the adhesive force between the dressing and body tissues is enhanced, so that the dressing can repair itself and protect the wound surface from being polluted when the dressing is damaged by external force.
3. The aminated Pluronic F127 nano-micelle can efficiently deliver fat-soluble anti-skin cancer drugs to tumor tissues, the micelle can be fixed in a polymer network through chemical crosslinking, and crosslinking groups are degraded under the stimulation of the acidic environment of the tumor tissues, so that nano-micelle particles are released, and the purposes of controlled release and long-acting drug delivery of the drugs are achieved.
4. The raw materials adopted by the invention all have good biocompatibility, and the dressing for the antibacterial skin cancer chemotherapy also has good biocompatibility, so that the dressing has a good application prospect in repairing the wound surface of an infiltrated tissue which is difficult to excise and delivering a tumor inhibiting drug after a physical tumor excision operation.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate the understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and it will be apparent to those skilled in the art that various changes may be made without departing from the spirit and scope of the invention as defined and defined in the appended claims, and all matters produced by the invention using the inventive concept are protected.
Example 1
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 100mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 10mg of medicine are dissolved in 5ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min, wherein the medicine is a skin cancer resistant fat-soluble medicine;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.06MPa and the rotational evaporation temperature of 25 ℃ at the rotating speed of 300r/min for 30min to form a film;
c. heating the medicine film obtained in the step b at 40 ℃ until the medicine film is in a gel state, adding 5ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.1g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.12g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.06g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) Dissolving 110mg of amino-modified Pluronic F127 drug-loaded micelle particles in 5ml of normal saline, and stirring for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.57g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.5g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.3g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuing stirring, adding 0.15g of N-hydroxysuccinimide after 15min, pouring the solution into a tetrafluoroethylene mold after stirring for 1min, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 2
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 150mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 15mg of drug are dissolved in 7.5ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min, wherein the drug is an anti-skin cancer fat-soluble drug;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.065MPa and the rotational evaporation temperature of 28 ℃ and the rotational speed of 300r/min for 30min to form a film;
c. heating the medicinal membrane obtained in the step b at 45 ℃ until the medicinal membrane is in a gel state, adding 7.5ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated Pluronic F127 drug-loaded micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.15g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.18g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.09g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) Dissolving 165mg of amino modified Pluronic F127 drug-loaded micelle particles in 5ml of normal saline, and stirring for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.62g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.35g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.32g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuously stirring, adding 0.16g of N-hydroxysuccinimide after 15min, pouring the solution into a tetrafluoroethylene mold after stirring for 1min, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 3
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 200mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 20mg of the drug are dissolved in 10ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min, wherein the drug is a skin cancer resistant fat-soluble drug;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.07MPa and the rotational evaporation temperature of 32 ℃ at the rotating speed of 300r/min for 30min to form a film;
c. heating the medicinal membrane obtained in the step b at 50 ℃ until the medicinal membrane is in a gel state, adding 10ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated Pluronic F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.2g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, then adding 0.24g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.12g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) Dissolving 220mg of amino-modified Pluronic F127 drug-loaded micelle particles in 5ml of normal saline, and stirring for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.67g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.4g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.36g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuously stirring, adding 0.18g of N-hydroxysuccinimide after 15min, stirring for 1min, pouring the solution into a tetrafluoroethylene mold, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 4
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 250mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 25mg of a drug, which is an anti-skin cancer liposoluble drug, are dissolved in 12ml of acetonitrile solution and then magnetically stirred at a rotation speed of 100-200 r/min for 30 min;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.075MPa and the rotational evaporation temperature of 37 ℃ and the rotational speed of 300r/min for 30min to form a film;
c. heating the medicinal membrane obtained in the step b at 55 ℃ until the medicinal membrane is in a gel state, adding 12ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated Pluronic F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.25g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.10g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) 275mg of amino-modified Pluronic F127 drug-loaded micelle particles are dissolved in 5ml of normal saline, and stirred for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.72g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.45g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.4g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuously stirring, adding 0.2g of N-hydroxysuccinimide after 15min, stirring for 1min, and pouring the solution into a tetrafluoroethylene mold. Demoulding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 5
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 300mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 30mg of a drug are added into 15ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min, wherein the drug is a skin cancer resistant fat-soluble drug;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.08MPa and the rotational evaporation temperature of 40 ℃ at the rotating speed of 300r/min for 30min to form a film;
c. heating the medicinal membrane obtained in the step b at 40 ℃ until the medicinal membrane is in a gel state, adding 15ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated Pluronic F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.3g of acethydrazide trimethyl ammonium chloride in 12ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.36g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.18g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) Dissolving 330mg of amino-modified Pluronic F127 drug-loaded micelle particles in 5ml of normal saline, and stirring for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.77g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.5g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.5g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuously stirring, adding 0.25g of N-hydroxysuccinimide after 15min, pouring the solution into a tetrafluoroethylene mold after stirring for 1min, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 6
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 100mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 10mg of medicine are dissolved in 5ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min, wherein the medicine is a skin cancer resistant fat-soluble medicine;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.06MPa and the rotational evaporation temperature of 25 ℃ at the rotating speed of 300r/min for 30min to form a film;
c. heating the medicinal film obtained in the step b at 42 ℃ until the medicinal film is in a gel state, adding 5ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.1g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.12g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.06g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) Dissolving 110mg of amino-modified Pluronic F127 drug-loaded micelle particles in 5ml of normal saline, and stirring for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.68g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.56g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.3g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuing stirring, adding 0.15g of N-hydroxysuccinimide after 15min, pouring the solution into a tetrafluoroethylene mold after stirring for 1min, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Example 7
(1) Preparation of amino-modified Pluronic F127 drug-loaded micelle particles
a. 300mg of aminated Pluronic F127 (NH) was added at room temperature2-F127, Mn 12600g/mol) and 30mg of a drug which is an anti-skin cancer liposoluble drug are dissolved in 15ml of acetonitrile solution, and then the mixture is magnetically stirred for 30min at the rotating speed of 100-200 r/min;
b. rotationally evaporating the solution obtained in the step a at the pressure of 0.08MPa and the rotational evaporation temperature of 40 ℃ at the rotating speed of 300r/min for 30min to form a film;
c. heating the medicinal membrane obtained in the step b at 60 ℃ until the medicinal membrane is in a gel state, adding 12ml of physiological saline with the same temperature, fully hydrating, uniformly stirring, and freeze-drying to obtain powdery aminated Pluronic F127 medicine-carrying micelle particles;
(2) preparation of quaternized polyglutamic acids
Firstly, dissolving 1.47g of polyglutamic acid and 0.3g of acethydrazide trimethyl ammonium chloride in 15ml of normal saline, stirring for 15min at the rotating speed of 100-200 r/min, adding 0.36g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, stirring uniformly, adding 0.18g of N-hydroxysuccinimide after 5min, and reacting for 20 min;
and (II) dialyzing the solution obtained in the step (I) to remove 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and freeze-drying to obtain white flocculent quaternized polyglutamic acid.
(3) 275mg of amino-modified Pluronic F127 drug-loaded micelle particles are dissolved in 5ml of normal saline, and stirred for 15min at the rotating speed of 100-200 r/min;
(4) dissolving 1.75g of quaternized polyglutamic acid in 10ml of normal saline, adding 0.35g of tyramine hydrochloride, and stirring for 15min at the rotating speed of 100-200 r/min;
(5) and (3) adding the solution obtained in the step (3) into the solution obtained in the step (4), stirring for 10min at the rotating speed of 100-200 r/min, adding 0.4g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride after uniformly stirring, continuously stirring, adding 0.2g of N-hydroxysuccinimide after 15min, stirring for 1min, pouring the solution into a tetrafluoroethylene mold, and demolding after 2min to obtain the dressing for the antibacterial skin cancer chemotherapy.
Claims (6)
1. A preparation method of the dressing for antibacterial skin cancer chemotherapy is characterized by comprising the following steps:
(1) dissolving the amino-modified Pluronic F127 drug-loaded micelle particles in water to prepare an amino-modified Pluronic F127 drug-loaded micelle solution with the concentration of 2-6 wt%;
(2) dissolving 3-5 parts by mass of quaternized polyglutamic acid in water, adding 1 part by mass of tyramine hydrochloride, and preparing a polyglutamic acid solution with the concentration of 15-20 wt%;
(3) then, uniformly mixing the solutions obtained in the step (1) and the step (2) according to the volume ratio of 1:2 to obtain a mixed solution;
(4) then, adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide into the mixed solution obtained in the step (3), and stirring for 1-3 min to obtain dressing stock solution for the antibacterial skin cancer chemotherapy; in the dressing stock solution for the antibacterial skin cancer chemotherapy, the content of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride is 20-33.33 mg/ml, and the content of N-hydroxysuccinimide is 10-16.67 mg/ml;
(5) finally, pouring the dressing stock solution for the antibacterial skin cancer chemotherapy obtained in the step (4) into a mould, and demoulding after condensation to obtain the dressing for the antibacterial skin cancer chemotherapy;
wherein the preparation method of the quaternized polyglutamic acid in the step (2) comprises the following steps: dissolving 1.47 parts by mass of polyglutamic acid and 0.1-0.3 part by mass of acethydrazide trimethyl ammonium chloride in water to prepare a solution with the weight percent of 10-15, adding 0.12-0.36 part by mass of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, uniformly stirring, adding 0.06-0.18 part by mass of N-hydroxysuccinimide, reacting for 20-30 min, dialyzing to remove the 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and the N-hydroxysuccinimide, and freeze-drying to obtain white floccule, namely the quaternized polyglutamic acid.
2. The method for preparing a dressing for antibacterial skin cancer chemotherapy according to claim 1, wherein the amino-modified Pluronic F127 drug-loaded micelle particle in the step (1) is prepared as follows: dissolving 0.1-0.3 part by mass of amino-modified Pluronic F127 and 0.01-0.03 part by mass of drugs in 3.95-11.85 parts by mass of acetonitrile, performing rotary evaporation to obtain a drug membrane, placing the drug membrane at 40-60 ℃ to form a gel state, adding 5-15 parts by mass of water at the same temperature for hydration treatment, stirring uniformly, performing ultrasonic treatment to obtain amino-modified Pluronic F127 drug-loaded micelle solution, and performing freeze drying to obtain white powder, namely amino-modified Pluronic F127 drug-loaded micelle particles.
3. The method for preparing a dressing for antimicrobial skin cancer chemotherapy according to claim 2, wherein the drug is a skin cancer-resistant liposoluble drug.
4. The method for preparing a dressing for antibacterial skin cancer chemotherapy according to any one of claims 1 to 3, characterized in that the amino-modified Pluronic F127 is modified by terminal amination.
5. The method for preparing a dressing for antibacterial skin cancer chemotherapy according to any one of claims 1, 2 and 3, characterized in that the mass ratio of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride to N-hydroxysuccinimide added each time is 2: 1.
6. An antibacterial skin cancer chemotherapeutic dressing prepared by the method of any one of claims 1-5.
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