CN111035795A

CN111035795A - Formula of drug-loaded absorbable sponge and preparation method and application thereof

Info

Publication number: CN111035795A
Application number: CN201911366199.9A
Authority: CN
Inventors: 曹佩培; 赵中; 黄乃进
Original assignee: Hangzhou Welllead Medical Instrument Co ltd
Current assignee: Hangzhou Welllead Medical Instrument Co ltd
Priority date: 2019-12-26
Filing date: 2019-12-26
Publication date: 2020-04-21

Abstract

The invention discloses a formula of a drug-loaded absorbable sponge, a preparation method and application thereof, wherein the formula of the absorbable sponge comprises the following components in parts by mass: 0.0002-0.2 part of target drug, 20 parts of hexamethyl diisocyanate, 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, 2-100 parts of solvent, 80 parts of polyurethane chain extender and 200-10000 parts of 1, 4-dioxane; the formula of the invention ensures that the sponge has the effect of slowly releasing the medicament, so that the product has the functions of hemostasis and long-acting medicament slow release; the product has small damage to the mucosa of an operation cavity, reduces scar formation, tissue necrosis and postoperative adhesion; the product can fully adsorb pus, and reduce the treatment times of operative cavity and wound; because the loaded target drugs include: the product has the functions of diminishing inflammation and resisting edema and provides a good growth environment for new tissues.

Description

Formula of drug-loaded absorbable sponge and preparation method and application thereof

Technical Field

The invention relates to the field of medical materials, in particular to a formula of a drug-loading absorbable sponge, a preparation method and application thereof.

Background

With the development of science and technology, various novel dressings are continuously appeared, such as gelatin hemostatic sponge, polyvinyl alcohol hemostatic sponge, absorbent cotton, alginate dressing and the like. In order to treat wounds more effectively while protecting the wound surface, the dressing is required to cover the wound surface and also have the function of promoting tissue repair; meanwhile, the biodegradable film also has biodegradability, and can reduce the dressing change times.

However, in the field of hemostasis and functional repair, there is still a lack of an absorbable drug-loaded hemostatic sponge having hemostatic function and regulating and controlling the repair function of damaged tissue.

The market needs an absorbable sponge which has the functions of hemostasis and long-acting drug slow release, can adapt to irregular space of a wound surface and provides a good growth environment for new tissues, and the invention solves the problems.

Disclosure of Invention

In order to solve the defects of the prior art, the invention aims to provide the formula of the medicine-carrying absorbable sponge, the preparation method and the application thereof.

In order to achieve the above object, the present invention adopts the following technical solutions:

the formula of the drug-carrying absorbable sponge comprises the following components in parts by weight: 0.0002-0.2 part of target drug, 20 parts of hexamethyl diisocyanate, 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, 2-100 parts of solvent, 80 parts of polyurethane chain extender and 200-10000 parts of 1, 4-dioxane.

The formula of the drug-carrying absorbable sponge comprises the following target drugs: glucocorticoid drugs, antihistamine drugs.

The formula of the drug-carrying absorbable sponge comprises the following solvents: ethanol, acetone, N-hexane, petroleum ether, chloroform, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide and N, N-dimethylformamide.

A preparation method of a medicine-carrying absorbable sponge comprises the following steps:

step one, pretreatment of a target drug:

weighing a target drug, adding the target drug into a solvent, sealing and ultrasonically dissolving to prepare a target drug solution for later use;

step two, preparing an absorbable sponge precursor solution:

weighing 20 parts of hexamethyl diisocyanate and 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, sequentially adding the hexamethyl diisocyanate and the DL-lactide-co-epsilon-caprolactone copolymer into a flask containing 100ml of N, N-dimethylformamide, reacting for 3 hours, filtering to remove excessive hexamethyl diisocyanate, and purifying to obtain a macromolecular diisocyanate prepolymer;

weighing 80 parts of polyurethane chain extender, adding the polyurethane chain extender and the purified macromolecular diisocyanate prepolymer into a solution containing 200ml of 1, 4-dioxane, reacting for 15 hours until the reaction system becomes viscous, and diluting the viscous reaction system with the 1, 4-dioxane solution to obtain an absorbable sponge precursor solution;

and step three, preparing the absorbable sponge loaded with the target drug.

The preparation method of the drug-loaded absorbable sponge comprises the following steps:

weighing poly-epsilon-caprolactone, adding into the prepared target drug solution, mixing uniformly, adding the mixed solution into the absorbable sponge precursor solution, filtering, freezing at-20 ℃, and freeze-drying to obtain the absorbable sponge loaded with the target drug.

one, preparing a blank absorbable sponge:

filtering the absorbable sponge precursor solution through a sterile filter membrane, putting the solution into a freeze-drying plate, freezing at-20 ℃, freeze-drying by using a vacuum freeze-drying machine, and cutting the solution into required sizes by using a slicer to obtain blank absorbable sponge;

secondly, spraying the medicine on the surface of the blank absorbable sponge:

and spraying the prepared target drug solution on the surface of the absorbable sponge by adopting drug spraying equipment after setting the spraying amount to be 2ml, the spraying speed to be 0.4ml/min and the receiving distance to be 20mm, thus obtaining the absorbable sponge loaded with the target drug.

step one, pretreatment of a target drug:

step two, preparing the absorbable sponge precursor solution loaded with the target drug:

weighing 20 parts of hexamethyl diisocyanate and 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, adding the hexamethyl diisocyanate and 80 parts of DL-lactide-co-epsilon-caprolactone copolymer together with a prepared target medicine solution into 100ml of N, N-dimethylformamide, filtering to remove excessive hexamethyl diisocyanate after reacting for 3 hours, and purifying to obtain a macromolecular diisocyanate prepolymer;

weighing 80 parts of polyurethane chain extender, adding the polyurethane chain extender and the purified macromolecular diisocyanate prepolymer into a solution containing 200ml of 1, 4-dioxane, reacting for 15 hours until the reaction system becomes viscous, and diluting the viscous reaction system with the 1, 4-dioxane solution to obtain an absorbable sponge precursor solution carrying the target medicament;

step three, preparing absorbable sponge loaded with target drugs;

filtering the absorbable sponge precursor solution loaded with the target drug by using an aseptic filter membrane, putting the filtered absorbable sponge precursor solution into a freeze-drying plate, freezing at-20 ℃, and freeze-drying by using a vacuum freeze-drying machine to obtain the absorbable sponge loaded with the target drug.

The utility model provides an use of medicine carrying absorbable sponge, medicine carrying absorbable sponge includes according to the part by mass: 0.0002-0.2 part of target drug, 20 parts of hexamethyl diisocyanate, 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, 2-100 parts of solvent, 80 parts of polyurethane chain extender and 200-10000 parts of 1, 4-dioxane; the target drugs include: glucocorticosteroids, antihistamines; the medicine-carrying absorbable sponge is used for nasal cavity hemostasis, anti-inflammation and anti-edema.

The invention has the advantages that:

the formula of the invention ensures that the sponge has the effect of slowly releasing the medicament, so that the product has the functions of hemostasis and long-acting medicament slow release;

the product has flexible texture, has small damage to the mucosa of the operative cavity, can adapt to the irregular space of the wound surface, does not influence the epithelization of the mucosa and the healing of the wound, and has the effects of reducing the formation of scars, tissue necrosis, postoperative adhesion and the like;

the product can fully adsorb pus, reduce the treatment times of operative cavity and wound, and obviously relieve the pain and economic burden of patients;

because the loaded target drugs include: glucocorticosteroids, antihistamines, glucocorticosteroids; the product has the functions of diminishing inflammation and resisting edema, provides a good growth environment for the new tissue and further meets the clinical requirement.

Drawings

FIG. 1 is an optical microscope photograph of a blank absorbable sponge magnified 40 times;

FIG. 2 is an optical microscope photograph at 40X magnification of an absorbable sponge loaded with mometasone furoate prepared in example 1;

FIG. 3 is a graph of drug loading data for blank absorbable sponges prepared in examples 2, 3, 5, and 6;

FIG. 4 is a graph showing the in vitro release profiles of the drug loaded absorbable sponges prepared in examples 1-6, respectively loaded with mometasone furoate.

Detailed Description

The invention is described in detail below with reference to the figures and the embodiments.

Example 1

(1) Pretreatment of a target drug:

accurately weighing 100mg of mometasone furoate medicine powder, then adding the powder into 20ml of absolute ethyl alcohol, sealing and ultrasonically dissolving to prepare a target medicine solution for later use;

(2) preparing an absorbable sponge precursor solution:

weighing 20g of hexamethyl diisocyanate and 80g of DL-lactide-co-epsilon-caprolactone copolymer, sequentially adding the hexamethyl diisocyanate and the DL-lactide-co-epsilon-caprolactone copolymer into a flask containing 100ml of N, N-dimethylformamide, reacting at the temperature of 70 ℃ for 3 hours at the rotating speed of 300r/min, removing excessive hexamethyl diisocyanate at the temperature of 65 ℃ through reduced pressure filtration, and purifying to obtain a macromolecular diisocyanate prepolymer; and then weighing 80g of polyurethane chain extender, adding the polyurethane chain extender and the purified macromolecular diisocyanate prepolymer into a flask containing 200ml of 1, 4-dioxane solution together, reacting at the rotating speed of 300r/min and the temperature of 70 ℃ for 15 hours, then enabling a reaction system to become viscous, diluting with a proper amount of 1, 4-dioxane solution, and diluting with 1, 4-dioxane until the mass concentration of the polymer in the solution is 1.8% when the viscosity of the solution is not increased any more, thus obtaining the absorbable sponge precursor solution.

(3) Preparing an absorbable sponge loaded with the target drug:

accurately weighing 1g of poly-epsilon-caprolactone, adding the poly-epsilon-caprolactone into a prepared target drug solution, ultrasonically mixing the poly-epsilon-caprolactone uniformly, adding the mixed solution into an absorbable sponge precursor solution, filtering the solution through a sterile filter membrane, putting the filtered solution into a freeze-drying tray, freezing the frozen solution at the temperature of-20 ℃, and then freeze-drying the frozen solution by using a vacuum freeze-drying machine to obtain the absorbable sponge carrying the target drug, wherein the absorbable sponge is shown in figure 2.

Example 2

(1) Pretreatment of a target drug:

accurately weighing 0.5mg of budesonide drug powder, adding the budesonide drug powder into 3ml of tetrahydrofuran, sealing and ultrasonically dissolving to prepare a target drug solution for later use;

(2) preparing an absorbable sponge precursor solution:

(3) Preparing a blank absorbable sponge:

filtering absorbable sponge precursor solution with sterile filter membrane, freezing at-20 deg.C in freeze-drying tray, freeze-drying with vacuum freeze-drying machine, and cutting into required size with slicer to obtain blank absorbable sponge, as shown in FIG. 1.

(4) Preparing an absorbable sponge loaded with the target drug:

soaking the blank absorbable sponge into the prepared target drug solution, putting the blank absorbable sponge into a freeze-drying plate after the blank absorbable sponge completely absorbs the drug solution, freezing at-20 ℃, and freeze-drying by using a vacuum freeze-drying machine to obtain the absorbable sponge loaded with the target drug.

Example 3

(1) Pretreatment of a target drug:

accurately weighing 0.5mg of triamcinolone acetonide medicine powder, then adding the triamcinolone acetonide medicine powder into 2ml of absolute ethyl alcohol, sealing and ultrasonically dissolving to prepare a target medicine solution for later use;

(2) preparing an absorbable sponge precursor solution:

(3) Preparing a blank absorbable sponge:

filtering the absorbable sponge precursor solution through a sterile filter membrane, putting the solution into a freeze-drying plate, freezing at-20 ℃, freeze-drying by using a vacuum freeze-drying machine, and cutting the solution into required sizes by using a slicer to obtain the blank absorbable sponge.

(4) Preparing an absorbable sponge loaded with the target drug:

and (3) spraying the prepared target drug solution on the surface of a blank absorbable sponge by adopting drug spraying equipment after setting the spraying amount to be 2ml, the spraying speed to be 0.4ml/min and the receiving distance to be 20mm, thus obtaining the absorbable sponge loaded with the target drug.

Example 4

(1) Pretreatment of a target drug:

accurately weighing 200mg of fluticasone propionate medicinal powder, then adding the medicinal powder into 20ml of N, N-dimethylformamide, sealing and ultrasonically dissolving to prepare nasal corticosteroid hormone medicinal solution for later use;

(2) preparing an absorbable sponge precursor solution:

weighing 20g of hexamethyl diisocyanate and 80g of DL-lactide-co-epsilon-caprolactone copolymer, adding the hexamethyl diisocyanate and 80g of DL-lactide-co-epsilon-caprolactone copolymer together with a prepared nasal corticosteroid hormone drug solution into a flask containing 100ml of N, N-dimethylformamide, reacting for 3 hours at the temperature of 70 ℃ at the rotating speed of 300r/min, removing excessive hexamethyl diisocyanate at the temperature of 65 ℃ through reduced pressure filtration, and purifying to obtain a drug-loaded macromolecular diisocyanate prepolymer; and then weighing 80g of polyurethane chain extender, adding the polyurethane chain extender and the purified drug-loaded macromolecular diisocyanate prepolymer into a flask containing 200ml of 1, 4-dioxane solution together, reacting for 15 hours at the temperature of 70 ℃ at the rotating speed of 300r/min, wherein the reaction system becomes viscous, diluting with a proper amount of 1, 4-dioxane solution, and diluting with 1, 4-dioxane until the mass concentration of the polymer in the solution is 1.8% when the viscosity of the solution is not increased, thus obtaining the absorbable sponge precursor solution loaded with the target drug.

(3) Preparing an absorbable sponge loaded with the target drug:

Example 5

(1) Pretreatment of a target drug:

accurately weighing 0.2mg of cetirizine medicine powder, then adding the cetirizine medicine powder into 3ml of trichloromethane, sealing and ultrasonically dissolving to prepare a target medicine solution for later use;

(2) preparing an absorbable sponge precursor solution:

weighing 20g of gelatin and 80g of purified water, dissolving for 30min at the rotation speed of 300r/min and the temperature of 70 ℃, then adding 30ml of formaldehyde solution, adjusting the rotation speed to 1000r/min, and then continuously stirring for 4h to obtain the absorbable sponge precursor solution.

(3) Preparing a blank absorbable sponge:

(4) Preparing an absorbable sponge loaded with the target drug:

Example 6

(1) Pretreatment of a target drug:

accurately weighing 0.4mg of fexofenadine medicine powder, adding the fexofenadine medicine powder into 3ml of chloroform, sealing and ultrasonically dissolving to prepare a target medicine solution for later use;

(2) preparing an absorbable sponge precursor solution:

weighing 20g of sodium alginate, dissolving the sodium alginate in 80g of purified water, and uniformly mixing for 30min at the rotation speed of 300r/min and the temperature of 50 ℃ to obtain the absorbable sponge precursor solution.

(3) Preparing a blank absorbable sponge:

filtering the absorbable sponge precursor solution through a sterile filter membrane, putting the solution into a freeze-drying plate, freezing at-20 ℃, freeze-drying by using a vacuum freeze-drying machine, and cutting the solution into required sizes by using a slicer to obtain blank absorbable sponge precursors; and then immersing the blank absorbable sponge into the prepared calcium chloride aqueous solution for 6 hours, taking out the blank absorbable sponge, washing the blank absorbable sponge with deionized water for multiple times, and performing freeze drying treatment again to obtain the blank absorbable sponge.

(4) Preparing an absorbable sponge loaded with the target drug:

and (3) immersing the blank absorbable sponge into the prepared target drug solution for 12h, taking out the blank absorbable sponge, wiping off redundant drug liquid on the surface, and drying the blank absorbable sponge at 50 ℃ for 24h to obtain the absorbable sponge loaded with the target drug.

Experiment one, a drug loading test;

the experimental process comprises the following steps:

(1) cutting and accurately weighing 0.5g of blank absorbable sponge obtained in the embodiments 2, 3, 5 and 6 respectively for later use;

(2) accurately weighing four parts of mometasone furoate medicine, wherein each part is 0.1g, and dissolving into 10ml of absolute ethyl alcohol respectively to prepare mometasone furoate medicine solution for later use;

(3) respectively immersing the blank sponge into mometasone furoate medicinal solution for 10 minutes, taking out after the blank sponge is completely imbibed, and removing the redundant medicinal solution on the surface;

(4) and (3) respectively putting the four samples into a vacuum drying oven, drying for 24 hours at room temperature, taking out and weighing to obtain the weight of the sponge after drug loading, and finally calculating the drug loading percentages of the four samples.

The results of the experiment are shown in table 1 and fig. 3.

TABLE 1

	Drug loading (%)
		Example 2	16.1
Example 3	15.8
		Example 5	6.7
Example 6	5.7

And (4) analyzing results: the product obtained by adopting the formula and the method has remarkable excellent drug loading rate.

Experiment two, drug release test;

the experimental process comprises the following steps:

(1) accurately weighing 0.5g of the absorbable sponges loaded with mometasone furoate medicaments obtained in examples 1, 2, 3, 4, 5 and 6 respectively;

(2) putting the six samples into conical flasks with plugs, which contain 100ml of PBS buffer solution containing 0.5% of Tween-80, and carrying out constant-temperature water bath at 37 ℃;

(3) taking 5ml of solution every 8 hours, simultaneously supplementing 5ml of new PBS buffer solution containing tween-80, and sampling 15 samples in each group according to the drug release time;

(4) and (4) determining the drug content in the solution by using a high performance liquid chromatography analysis system, and analyzing to obtain the release condition of the drug.

The results of the experiment are shown in FIG. 4.

And (4) analyzing results: the product obtained by adopting the formula and the method has remarkable and excellent slow release function and uniform release speed.

The sponge has the effect of slowly releasing the medicament, can adapt to irregular space of a wound surface, can fully adsorb pus, reduces the treatment times of an operative cavity and the wound, has the functions of diminishing inflammation and resisting edema, and provides a good growth environment for new tissues.

The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It should be understood by those skilled in the art that the above embodiments do not limit the present invention in any way, and all technical solutions obtained by using equivalent alternatives or equivalent variations fall within the scope of the present invention.

Claims

1. The formula of the drug-carrying absorbable sponge is characterized by comprising the following components in parts by mass: 0.0002-0.2 part of target drug, 20 parts of hexamethyl diisocyanate, 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, 2-100 parts of solvent, 80 parts of polyurethane chain extender and 200-10000 parts of 1, 4-dioxane.

2. The formulation of a drug-loaded absorbable sponge according to claim 1, wherein the target drug comprises: glucocorticoid drugs, antihistamine drugs.

3. The formulation of claim 1, wherein the solvent comprises: ethanol, acetone, N-hexane, petroleum ether, chloroform, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide and N, N-dimethylformamide.

4. A preparation method of a medicine-carrying absorbable sponge is characterized by comprising the following steps:

step one, pretreatment of a target drug:

step two, preparing an absorbable sponge precursor solution:

and step three, preparing the absorbable sponge loaded with the target drug.

5. The method for preparing a drug-loaded absorbable sponge according to claim 4, wherein in step three, an absorbable sponge loaded with a target drug is prepared:

6. The method for preparing a drug-loaded absorbable sponge according to claim 4, wherein in step three, an absorbable sponge loaded with a target drug is prepared:

one, preparing a blank absorbable sponge:

secondly, spraying the medicine on the surface of the blank absorbable sponge:

7. A preparation method of a medicine-carrying absorbable sponge is characterized by comprising the following steps:

step one, pretreatment of a target drug:

step three, preparing absorbable sponge loaded with target drugs;

8. The application of the drug-carrying absorbable sponge is characterized in that the drug-carrying absorbable sponge comprises the following components in parts by mass: 0.0002-0.2 part of target drug, 20 parts of hexamethyl diisocyanate, 80 parts of DL-lactide-co-epsilon-caprolactone copolymer, 2-100 parts of solvent, 80 parts of polyurethane chain extender and 200-10000 parts of 1, 4-dioxane; the target drugs include: glucocorticosteroids, antihistamines; the medicine-carrying absorbable sponge is used for nasal cavity hemostasis, anti-inflammation and anti-edema.