CN111870733B

CN111870733B - Antibacterial sealing composite material applied to anorectal surgical operation wound surface and preparation method thereof

Info

Publication number: CN111870733B
Application number: CN202010816363.8A
Authority: CN
Inventors: 吴建华; 姚江平
Original assignee: Hangzhou Yiwen Biomedical Co ltd
Current assignee: Hangzhou Yiwen Biomedical Co ltd
Priority date: 2020-08-14
Filing date: 2020-08-14
Publication date: 2022-04-08
Anticipated expiration: 2040-08-14
Also published as: CN111870733A

Abstract

The invention provides an antibacterial sealing composite material applied to a wound surface of anorectal surgery, which comprises a first composition and a second composition, wherein the first composition comprises a primary amino-terminated branched polylysine bonded carboxymethyl aminodextran, a primary amino-terminated branched polylysine bonded branched polydextrose and an antibacterial agent, and the second composition is a modified branched polydextrose multi-site crosslinking agent and a maleimide-terminated eight-arm polyethylene glycol crosslinking agent or the modified branched polydextrose multi-site crosslinking agent and a succinimide-group-terminated eight-arm polyethylene glycol crosslinking agent. The antibacterial sealing composite material applied to the wound surface of the anorectal surgery can seal the wound surface after the anorectal surgery, has a good antibacterial effect, greatly promotes the healing of the wound surface of the anorectal surgery, shortens the repair period, has strong clinical operability and simple and convenient use, and can be instantly formed in situ of the wound surface.

Description

Antibacterial sealing composite material applied to anorectal surgical operation wound surface and preparation method thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an antibacterial closed composite material applied to a wound surface of anorectal surgery and a preparation method thereof.

Background

In anorectal surgery, particularly related surgery such as external hemorrhoid, internal hemorrhoid, mixed hemorrhoid, anal fistula, perianal abscess and the like, redundant or pathological tissues need to be cut off in the surgery process, a large area of wound surface is often generated after surgery, and the wound surface has obvious bleeding, bleeding and weeping problems. One part of the wound surfaces is in the anus and intestine or near the anus, the other part of the wound surfaces is at the contact position of the human hip and contraposition substances in the lying or sitting process, the two wound surfaces are always extruded, rubbed and pulled frequently, due to the particularity of the wound surfaces, the wound surfaces not only bring difficulty to clinical nursing, but also bring great stimulation, pain and discomfort to patients, and even the patients are affected by different degrees in daily lying, lying and sitting postures. Meanwhile, due to the factors that the wound surface is positioned in the anus and intestine, the anus and the position near the anus, the wound surface is easily infected by bacteria and viruses, and the healing of the wound surface is further influenced. Under the current medical technology level, a patient usually needs to be close to one month or even longer from the beginning of an operation to the healing of a wound surface, the recurrence is strong, all aspects of diet daily life need to be paid attention to so as to relieve pain, discomfort, swelling, foreign body sensation and the like caused by the wound surface, and the life quality is obviously reduced in the healing period.

At present, the treatment mode of the wound surface after anorectal surgery related to external hemorrhoid, internal hemorrhoid, anal fistula, perianal abscess and the like is mainly to coat ointment or liquid medicine after partial suture or electric coagulation and replace the ointment or liquid medicine in the postoperative period. The main reasons for the poor performance of these post-operative treatment modalities are: (1) on the contrary, the wound surface is always exposed to the stimulation environment, such as extrusion and friction between the wound surface and the peripheral wound surface, extrusion and friction between the wound surface and the peripheral non-wound surface, and stimulation of the plaster to the wound surface, and these adverse factors damage the repair of the wound surface to different degrees, thereby delaying the healing of the wound surface. (2) The wound surface is not closed, and is easily infected by anorectal bacteria, perianal bacteria and viruses to cause the problems of inflammation, effusion, seepage and the like. (3) The wound healing period is long, the stimulation and extrusion frequency of daily life living processes such as sitting, lying and lying on the wound are increased, and the wound healing is not facilitated.

Disclosure of Invention

An object of the application is to provide an antibiotic closed composite material who is applied to anus enterochirurgia operation surface of a wound and its preparation method, it can be used to external hemorrhoid, internal hemorrhoid, anal fistula, relevant anus enterochirurgia such as perianal abscess postoperative surface of a wound seals and is antibiotic, self restoration for the surface of a wound provides a good protective environment, promote the healing of the surface of a wound, not only reduced the clinical nursing degree of difficulty to relevant surface of a wound, and greatly shortened the healing cycle, and simultaneously, in the postoperative healing cycle, patient's quality of life has also been promoted greatly.

In a first aspect, embodiments of the present application provide an antibacterial sealing composite material for application to a wound surface of anorectal surgery, including a first composition and a second composition, the first composition includes a primary amino-terminated branched polylysine bonded carboxymethyl aminodextran, a primary amino-terminated branched polylysine bonded branched polyglucose, and an antibacterial agent, and the second composition is a modified branched polyglucose multi-site cross-linking agent and a maleimide-terminated eight-arm polyethylene glycol cross-linking agent, or a modified branched polyglucose multi-site cross-linking agent and a succinimide-group-terminated eight-arm polyethylene glycol cross-linking agent.

Preferably, the antimicrobial agent comprises at least one of didecyldimethyl ammonium chloride, didecyldimethyl ammonium bromide, chlorhexidine acetate, chlorhexidine gluconate, benzalkonium chloride, peroxyacetic acid, benzalkonium bromide, and dibromohydantoin.

Preferably, the primary amino-terminated branched polylysine is bonded to the carboxymethyl aminodextran by amide bonding, wherein the number of the branched polylysine molecules bonded to each carboxymethyl aminodextran is at least 25, and the primary amino-terminated branched polylysine has 8 or 16 branches, each branch having only one primary amino group at its end.

Preferably, the branched polyglucose bonded by the primary amino-terminated branched polylysine is formed by bonding the primary amino-terminated branched polylysine and the branched polyglucose through an amide bond, wherein the number of the branched polylysine molecules bonded on each branched polyglucose is at least 15, the primary amino-terminated branched polylysine has 8 or 16 branches, and each branch has only one primary amino group at the end.

Preferably, the carboxymethyl aminodextran has an average molecular weight of 200000 daltons or more.

Preferably, the carboxymethyl aminodextran has a degree of substitution of carboxymethyl group of 0.75 or more.

Preferably, the branched polyglucose multi-site cross-linker comprises one of an aldehyde group, an acrylate group, a succinimide ester group and a maleimide group.

In a second aspect, an embodiment of the present application provides a method for preparing an antibacterial sealing composite material for an anorectal surgical wound, including the following steps:

s1: dissolving and dispersing the anti-inflammatory drug or the antibiotic in the buffer solution of the first composition;

s2: dissolving the first composition in a first composition buffer solution to obtain a first composition solution;

s3: dissolving the second composition in a second composition buffer solution to obtain a second composition solution;

s4: and (3) contacting and mixing the first composition solution and the second composition solution to form the antibacterial closed composite material.

Preferably, the anti-inflammatory agent comprises at least one of sodium chloride, ibuprofen, diclofenac, naproxen sodium, metronidazole, tinidazole, ornidazole, aspirin, acetaminophen and indomethacin piroxicam.

Preferably, the antibiotic comprises at least one of cefaclor, ceftazidime, cefdinir, cephalexin, erythromycin, ciprofloxacin, ofloxacin, mupirocin, fusidic acid, cortisone, hydrocortisone, and dexamethasone.

Preferably, the primary amino-terminated branched polylysine-bonded carboxymethyl aminodextran and the primary amino-terminated branched polylysine-bonded branched polyglucose in the first composition solution are in mass concentrations of 0.8% to 3.0% and 0.5% to 2.0%, respectively, and the total mass concentration of the two is not more than 4.0%.

Preferably, the mass concentration of the second composition in the second composition solution is 1.0% to 3.5%.

The antibacterial closed composite material applied to the wound surface of anorectal surgery takes the aminodextran as one of main raw materials, and the aminodextran has the characteristics of antibacterium and bacteriostasis. The first composition and the second composition are instantly crosslinked in situ (crosslinking reaction time is less than or equal to 1s) of the postoperative wound surface to form the sealing gel, the shape of the sealing gel is fixed, loss of the aminodextran is prevented, and the aminodextran continuously exists on the wound surface and exerts an antibacterial effect. Because a large number of and types of bacterial viruses exist in the anus and the anus, other antibacterial disinfectants with specificity and antibacterial performance, such as didecyl dimethyl ammonium chloride, didecyl dimethyl ammonium bromide, chlorhexidine acetate, glucose chlorhexidine, benzalkonium chloride, benzalkonium bromide, dibromohydantoin and the like are combined in the first composition, so that the antibacterial effect of the composite material can be enhanced. It is worth noting that these antibacterial disinfectants are not compatible with aminodextran, because these antibacterial disinfectants and aminodextran both have positive charge characteristics, further, these antibacterial disinfectants have compatibility with other polysaccharides such as sodium hyaluronate, carboxymethyl cellulose, sodium alginate, etc., because these antibacterial disinfectants have negative charge characteristics. And a certain amount of anti-inflammatory drugs and/or antibiotics can be added into the first composition according to the diagnosis and treatment of the actual condition of a patient, and the composite material can play a role of drug slow release on the wound surface and promote the wound surface to heal.

The invention relates to an antibacterial sealing composite material applied to a wound surface of anorectal surgery, which comprises a first composition and a second composition, wherein a plurality of branches are arranged on a primary amino-terminated branched polylysine bonded carboxymethyl aminodextran and a primary amino-terminated branched polylysine bonded branched polyglucose in the first composition, and active groups are contained at the tail ends of the branches, so that the antibacterial sealing composite material can be chemically reacted with a modified branched polyglucose multi-site cross-linking agent and a maleimide-terminated eight-arm polyethylene glycol cross-linking agent of the second composition, or the modified branched polyglucose multi-site cross-linking agent and a succinimide-group-terminated eight-arm polyethylene glycol cross-linking agent. Because the first composition contains a large number of branched chains and active groups, the modified branched polydextrose multi-site cross-linking agent in the second composition contains branches and multiple cross-linking sites, and the maleimide-terminated eight-arm polyethylene glycol cross-linking agent and the succinimide ester-terminated eight-arm polyethylene glycol cross-linking agent both have eight cross-linking sites, the first composition and the second composition are instantly cross-linked in situ (cross-linking reaction time is less than or equal to 1s) on the wound surface after operation to form a sealing adhesive, the wound surface can be completely sealed in situ, the wound surface is completely isolated from the outside, a good protective environment is provided for the healing of the wound surface, and the wound surface can be quickly repaired by a human body. When the composite material is used for sealing the postoperative wound surface, the composite material is difficult to displace due to seamless fit and good adhesion with the wound surface, and can provide a long-time protection effect. Because the wound surface is sealed, the stimulation of the outside to the wound surface is slowed down or even eliminated, the life quality of the patient during the postoperative rehabilitation period is improved, and the healing of the wound surface is indirectly further promoted. However, in the traditional treatment method, the wound surface has no protective repair environment, and the wound surface is damaged while being repaired in the self-repair process, so that the healing period is greatly prolonged. The composite material can implement comprehensive sealing of the wound surface in situ because: before use, the first composition solution and the second composition solution are both strong-flowing liquids, can cover along with the shape and appearance of a wound surface, and can instantly generate a cross-linking reaction when being contacted with the second composition, so that a sealing glue with a fixed shape and a certain thickness is formed in situ.

Drawings

The accompanying drawings are included to provide a further understanding of the embodiments and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments and together with the description serve to explain the principles of the invention. Other embodiments and many of the intended advantages of embodiments will be readily appreciated as they become better understood by reference to the following detailed description. The elements of the drawings are not necessarily to scale relative to each other. Like reference numerals designate corresponding similar parts.

FIG. 1 is a G2-8NH according to one embodiment of the invention₂A schematic molecular structure diagram of branched polylysine;

FIG. 2 is a block diagram of G3-16NH according to one embodiment of the present invention₂A schematic molecular structure diagram of branched polylysine;

FIG. 3 is a schematic representation of the molecular structure of a carboxymethyl aminodextran according to one embodiment of the present invention;

FIG. 4 is a schematic diagram of the molecular structure of branched polydextrose according to one embodiment of the present invention;

FIG. 5 is a schematic representation of the molecular structure of an eight-arm polyethylene glycol according to one embodiment of the present invention;

FIG. 6 is a schematic representation of the molecular structure of an eight-arm polyethylene glycol carboxylic acid according to one embodiment of the present invention;

FIG. 7 is a G2-8NH representation according to one embodiment of the present invention₂A molecular structure diagram of the branched polylysine bonded carboxymethyl aminodextran;

FIG. 8 is a schematic representation of a system according to the inventionOne embodiment G3-16NH₂A molecular structure diagram of the branched polylysine bonded carboxymethyl aminodextran;

FIG. 9 is a G2-8NH representation according to one embodiment of the present invention₂A molecular structure diagram of branched polyamide-amine bonded branched polydextrose;

FIG. 10 is a schematic representation of the molecular structure of a maleimide-terminated eight-armed polyethylene glycol, in accordance with one embodiment of the present invention;

FIG. 11 is a schematic representation of the molecular structure of a succinimide ester group terminated eight-armed polyethylene glycol carboxylic acid, according to one embodiment of the present invention;

FIG. 12 is a schematic diagram of the molecular structure of a maleimide-modified branched polydextrose in accordance with one embodiment of the present invention;

FIG. 13 is a schematic representation of the molecular structure of oxidized branched polydextrose according to one embodiment of the present invention;

FIG. 14(1) is a schematic illustration of the status of a hemorrhoid surgical wound of a patient after debridement according to one embodiment of the present invention;

FIG. 14(2) is a schematic representation of the condition of a 7-day postoperative wound using the antimicrobial occlusive composite material of the present invention after debridement of a patient's hemorrhoid surgical wound, according to one embodiment of the present invention;

FIG. 14(3) is a schematic representation of the condition of a 12 day post-operative wound of a patient without the antimicrobial occlusive composite material of the present invention following debridement of the hemorrhoid surgical wound, in accordance with one embodiment of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention clearer, the present invention will be described in further detail with reference to the accompanying drawings, and it is apparent that the described embodiments are only a part of the embodiments of the present invention, not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

G2-8NH₂Obtaining branched polylysine (first)One of the raw materials of the composition)

G2-8NH₂Branched polylysine, which has 8 branches, wherein each branch end contains an amino active group, the molecular structure is shown in figure 1, and the generation number: g2 (second generation) available from wechen molecular new materials limited.

Example 2

G3-16NH₂Obtaining branched polylysine (one of the starting materials of the first composition)

G3-16NH₂Branched polylysine, which has 16 branches, wherein each branch end contains an amino active group, the molecular structure is shown in figure 2, and the generation number: g3 (third generation) available from wechen molecular new materials limited.

Example 3

Obtaining of carboxymethyl aminodextran (one of the starting materials of the first composition)

Carboxymethyl aminodextran, CAS No.: 83512-85-0, wherein the degree of substitution of carboxymethyl is more than or equal to 0.75, the molecular structure is shown in figure 3, and the product is purchased from Nantong Lvshen bioengineering Co.

Example 4

Obtaining branched polydextrose (one of the starting materials of the first composition)

Branched polydextrose, CAS No.: 9057-02-7, molecular structure shown in FIG. 4, purchased from Furuida pharmaceutical group.

Example 5

Obtaining of eight-arm polyethylene glycol (one of the starting materials of the second composition)

Eight-arm polyethylene glycol with molecular weight of 10000 Dalton or so, 8 branched chains, and molecular structure shown in FIG. 5 was purchased from Xiamen Sainuo Pong Biotech, Inc.

Example 6

Obtaining of eight-arm Carboxylic acids polyethylene glycol (one of the starting materials for the second composition)

Eight-arm polyethylene glycol carboxylic acid with average molecular weight of 10000 Dalton and 8 branched chains, and molecular structure shown in FIG. 6, was purchased from Xiamen Sainuo Pong Biotech, Inc.

Example 7

G2-8NH₂Preparation of branched polylysine-bonded carboxymethyl aminodextran (first composition component)

The main raw materials are as follows: carboxymethyl aminodextran of example 3, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC. HCl, CAS No.: 25952-53-8), N-hydroxysuccinimide (NHS, CAS No.: 6066-82-6), G2-8NH of example 1₂A branched polylysine.

The preparation principle is as follows: g2-8NH₂One of the amino groups on the branched polylysine and the carboxyl group on the carboxymethyl cellulose are chemically reacted under the catalysts of EDC.HCl and NHS to form a new amido bond (-CO-NH-), and G2-8NH is reacted₂The branched polylysine is bonded to the carboxymethyl aminodextran to form G2-8NH₂The branched polylysine is bonded to the carboxymethyl aminodextran.

(1) Dissolving 30 parts by mass of carboxymethyl aminodextran in 1000 parts by mass of purified water to form a carboxymethyl aminodextran solution, and controlling the temperature of the carboxymethyl aminodextran solution at 8-16 ℃;

(2) continuously adding 8-16 parts by mass of EDC.HCl and 3-6 parts by mass of NHS, and stirring for 15min at the temperature of 8-16 ℃;

(3) adding 8-16 parts by mass of G2-8NH₂Stirring and dissolving the branched polylysine, and continuously reacting for 2-6 h;

(4) dialyzing and purifying the reacted solution by a dialysis bag with molecular weight cutoff of about 8000 daltons;

(5) adding lactose and mannitol after purification, and freeze-drying with vacuum freezer to obtain porous fluffy G2-8NH₂The branched polylysine is bonded with carboxymethyl aminodextran, which is easily dissolved in water, and the molecular structure is shown in figure 7.

Example 8

G3-16NH₂Preparation of branched polylysine-bonded carboxymethyl aminodextran (first composition component)

The main raw materials are as follows: carboxymethyl aminodextran, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride from example 3Salts (EDC. HCl, CAS number 25952-53-8), N-hydroxysuccinimide (NHS, CAS number 6066-82-6), G3-16NH from example 2₂A branched polylysine.

The preparation principle is as follows: g3-16NH₂One of the amino groups on the branched polylysine reacts with the carboxyl group on the carboxymethyl cellulose under the catalyst of EDC.HCl and NHS to form a new amido bond (-CO-NH-), and G3-16NH₂The branched polylysine is bonded to the carboxymethyl aminodextran to form G3-16NH₂The branched polylysine is bonded to the carboxymethyl aminodextran.

(3) then adding 10-20 parts by mass of G3-16NH₂Stirring and dissolving the branched polylysine, and continuously reacting for 1-4 h;

(5) adding lactose and mannitol after purification, and freeze-drying with vacuum freezer to obtain G3-16NH with porous fluffy appearance₂The branched polylysine is bonded with carboxymethyl aminodextran, which is easily dissolved in water, and the molecular structure is shown in figure 8.

Example 9

G2-8NH₂Branched polyamidoamine bonded branched polydextrose

Raw materials: g2-8NH from example 1₂Branched polyamidoamine, branched polydextrose of example 4.

The preparation principle is as follows: firstly, oxidizing branched polydextrose by periodate to obtain aldehyde group; secondly, aldehyde group and primary amine can generate Schiff base reaction to form-C-N-bond, and then the-C-N-bond is reduced to-CH through the hydrogenation reduction of sodium borohydride₂-NH-bond, G2-8NH₂The branched polyamidoamine is bonded to the branched polydextrose to form G2-8NH₂Branched polyamidoamine bonded branched polydextrose.

The preparation process comprises the following steps:

(1) dissolving 200 parts by mass of branched polydextrose in 1000 parts by mass of dilute sulfuric acid solution (the pH value of the dilute sulfuric acid is 1.5-2.5);

(2) continuously adding 2-4 parts by mass of sodium periodate, stirring at 60 ℃ in a dark place, and continuously reacting for 12-24 hours;

(3) after the reaction is finished, freeze-drying by using a vacuum freezer to obtain oxidized branched polydextrose for later use;

(4) dissolving 100 parts by mass of oxidized branched polydextrose in 1000 parts by mass of dimethylformamide solvent at 40-60 ℃, recovering to room temperature after dissolving, and adding 2-5 mL of glacial acetic acid;

(5) continuously adding 25-50 parts by mass of G2-8NH₂Stirring and dissolving the branched polyamide-amine to form a mixed solution;

(6) continuously reacting for 12-24 h at room temperature, wherein G2-8NH₂The amino at the end of the branched polyamide-amine reacts with the aldehyde group on the oxidized branched polyglucose by Schiff base to form-CH-N-bond;

(7) slowly adding 5-10 parts by mass of sodium borohydride, continuously stirring, and carrying out hydrogenation reduction reaction for 60-200 min;

(8) dialyzing and purifying the reacted solution with dialysis bag with molecular weight cut-off of 3500 Dalton (remark: recovering, concentrating and purifying dialysate to obtain unreacted G2-8 NH)₂Branched polyamidoamines);

(9) adding lactose and mannitol after purification, and freeze-drying with vacuum freezer to obtain G2-8NH with porous fluffy appearance₂Branched polyamidoamine bonded branched polydextrose, which is readily soluble in water, has a molecular structure as shown in FIG. 9.

Example 10

Preparation of Maleimido-terminated eight-arm polyethylene glycol (second composition component)

Preparing raw materials: eight-arm polyethylene glycol (average molecular weight 10000), maleimidocaproic acid, dicyclohexylcarbodiimide (DCC, CAS number: 538-75-0), DPTS.

The preparation principle is as follows: carboxyl on maleimide caproic acid and hydroxyl on the eight-arm polyethylene glycol are subjected to esterification reaction under the action of catalysts of Dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine p-methylbenzenesulfonic acid (DPTS) (the catalyst and the dehydrating agent), and maleimide groups are introduced to the tail ends of branched chains of the eight-arm polyethylene glycol to form the maleimide group-terminated eight-arm polyethylene glycol.

The preparation process comprises the following steps:

(1) dissolving 60 parts by mass of octa-armed polyethylene glycol (average molecular weight 40000) in 1000 parts by mass of anhydrous dimethyl sulfoxide;

(2) adding 8-16 parts by mass of Dicyclohexylcarbodiimide (DCC) and 4 parts by mass of 4-dimethylaminopyridine p-methylbenzenesulfonic acid (DPTS) catalyst, and stirring for dissolving to form a mixed solution;

(3) adding 6-12 parts by mass of maleimide group into the mixed solution, and stirring for reaction for 12-48 h;

(4) after the reaction is finished, dialyzing and purifying by adopting a dialysis bag with molecular weight cutoff of about 3500 daltons;

(5) adding lactose and mannitol, and freeze-drying with vacuum freezer to obtain porous fluffy maleimide-terminated eight-arm polyethylene glycol with good solubility in water and molecular structure shown in FIG. 10.

Wherein, the preparation method of the 4-dimethylaminopyridine p-methylbenzene sulfonic acid (DPTS) catalyst comprises the following steps:

mixing 10 parts by mass of p-toluenesulfonic acid (PTSA) with 250 parts by mass of toluene, and distilling to remove water; 6.5 parts by mass of 4-Dimethylaminopyridine (DMAP) are dissolved in 70 parts by mass of hot toluene (60-80 ℃); adding the hot 4-dimethylaminopyridine solution into a p-toluenesulfonic acid solution, stirring and reacting for 4-8 hours at the temperature of 65 ℃, then cooling and filtering; then recrystallizing with dichloroethane solvent to obtain the 4-dimethylamino pyridine p-methyl benzene sulfonic acid (DPTS) with white needle-shaped appearance.

Example 11

Preparation of succinimide ester group-terminated eight-arm polyethylene glycol carboxylic acid (second composition component)

Preparing main raw materials: eight-arm polyethylene glycol carboxylic acid, N-hydroxysuccinimide of example 6 (NHS, CAS number: 6066-82-6).

The preparation principle is as follows: carboxyl on the eight-arm polyethylene glycol carboxylic acid reacts with N-hydroxysuccinimide under the action of a catalyst 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl), and a succinimide ester group is introduced on the eight-arm polyethylene glycol carboxylic acid.

The preparation process comprises the following steps:

(1) dissolving 100 parts by mass of eight-arm polyethylene glycol carboxylic acid, 6 parts by mass of N-hydroxysuccinimide and 15 parts by mass of EDC.HCl in 1200 parts by mass of dichloromethane/N, N-dimethylformamide (volume ratio is 4:2) to form a mixed solution;

(2) continuously reacting the mixed solution at the temperature of 0-20 ℃ for 12-36 h to generate succinimide ester group-terminated eight-arm polyethylene glycol carboxylic acid;

(3) after the reaction is finished, dialyzing and purifying by adopting a dialysis bag with molecular weight cutoff of about 3500 daltons;

(4) lactose was added after purification, and then freeze-dried using a vacuum freezer to obtain succinimidyl ester group-capped eight-armed polyethylene glycol carboxylic acid with porous fluffy appearance, the molecular structure of which is shown in fig. 11.

Example 12

Preparation of Maleimido-terminated branched polydextrose (second composition component)

Preparing raw materials: branched polydextrose, maleimidocaproic acid, DCC, DPTS from example 4.

The preparation principle is as follows: carboxyl on maleimide caproic acid and hydroxyl on branched polydextrose are subjected to esterification reaction under the action of catalysts of Dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine p-methylbenzenesulfonic acid (DPTS) (catalyst and dehydrating agent), and maleimide groups are introduced into the branched polydextrose.

The preparation process comprises the following steps:

(1) dissolving 50 parts by mass of branched polydextrose (average molecular weight of 50000) in 1000 parts by mass of anhydrous DMSO, adding 8-16 parts by mass of Dicyclohexylcarbodiimide (DCC) and 4 parts by mass of 4-dimethylaminopyridine p-methylbenzenesulfonic acid (DPTS) catalyst, and stirring to dissolve to form a mixed solution;

(2) adding 4-8 parts by mass of maleimide caproic acid into the mixed solution, and stirring for reaction for 12-48 h;

(3) after the reaction is finished, dialyzing and purifying by adopting a dialysis bag with molecular weight cutoff of about 8000 Dalton;

(4) adding lactose and mannitol after purification, and freeze-drying with vacuum freezer to obtain porous fluffy maleimide-terminated branched polydextrose, which is easily soluble in water and has molecular structure shown in FIG. 12.

Example 13

Preparation of Oxycobranched polydextrose (second composition component)

The main raw materials are as follows: branched polydextrose and sodium periodate

The preparation principle is as follows: oxidizing the sugar units of the branched polydextrose by the oxidation of sodium periodate to form oxidized branched polydextrose with a certain oxidation degree, wherein the oxidized branched polydextrose contains a certain number of aldehyde groups.

The preparation process comprises the following steps:

(1) dissolving 100 parts by mass of branched polydextrose in 1000 parts by mass of dilute sulfuric acid solution (the pH value of the dilute sulfuric acid is 1.5-2.5);

(2) adding 15-30 parts by mass of periodic acid, and reacting at 60 ℃ in a dark place for 12-24 hours;

(3) dialyzing and purifying the solution after reaction to remove impurities;

(4) after purification, the branched polyglucose was freeze-dried by a vacuum freezer to obtain a branched polyglucose having a porous and fluffy appearance, and the molecular structure thereof is shown in FIG. 13.

Example 14

Preparation of antibacterial sealing composite material applied to anorectal surgical wound surface, application of antibacterial sealing composite material to pig anorectal or perianal wound surface of pig and performance detection of antibacterial sealing composite material

1. The preparation of the antibacterial closed composite material applied to the surgical wound surface of anorectal surgery and the application of the antibacterial closed composite material to the wound surface of pig anorectal or pig perianal comprises the following steps:

s1: dissolving the first composition in a first buffer solution to obtain a first composition solution;

s2: dissolving the second composition in a second buffer solution to obtain a second composition solution;

s3: the first composition solution is uniformly coated or sprayed on a thin layer of the wound surface of the pig anus intestine or the pig anus periphery, the second composition solution is uniformly covered on the wound surface of the pig anus intestine or the pig anus periphery, and the first composition and the second composition are rapidly crosslinked in situ on the wound surface of the pig anus intestine or the pig anus periphery to form the antibacterial closed composite material.

2. The performance detection of the antibacterial closed composite material applied to the surgical wound surface of anorectal surgery on the wound surfaces of pig anorectal or pig perianal comprises the following steps:

(1) the property test method of the antibacterial closed composite material layer for the closure of the wound surface of the pig anorectum or the perianal wound of the pig comprises the following steps:

s1: cutting a pig anus intestine or pig anus periphery with the diameter of about 4cm, rubbing the pig anus intestine or the pig anus periphery with abrasive paper to generate a wound surface, and pricking about 12 needle holes on the wound surface of the pig anus intestine or the pig anus periphery with an injection needle so that water can freely pass through the needle holes;

s2: smearing or spraying a layer of first composition solution on the wound surface of the pig anus intestine or the pig anus periphery, and then smearing or spraying a layer of second composition solution on the wound surface to form an antibacterial closed composite material layer on the wound surface;

s3: forming water pressure of 500 mm-600 mm on the pig anorectal or the perianal wound of the pig;

s4: after 300s, it was observed whether there was significant water track penetrating the pig muscle tissue and dripping.

(2) The test method comprises the following steps:

test groups:

s1: taking inert materials, and preferably the inert materials are characterized in that: the inert material is made of stainless steel, the length is 6-10 cm, the width is 3-5 cm, the thickness is 0.3-0.5 cm, the inert material contains multiple holes, the holes penetrate through the upper surface and the lower surface, the pore size is 0.6 mm-1.2 mm, and the inert material is subjected to dry heat sterilization or wet heat sterilization;

s2: sterilizing the first composition and the second composition by moist heat sterilization or irradiation sterilization. After sterilization, respectively dissolving the first composition and the second composition in a sterilized first buffer solution and a sterilized second buffer solution to form a first composition solution and a second composition solution;

s3: forming an antibacterial closed composite material on the upper surface of the inert material;

s4: contacting the lower surface of the inert material of S3 with sterilized medium; (Note: S3 the lower surface of the inert material and the space below the lower surface are always in a sterile environment)

S5: the upper surface of the inert material of S3 is in a bacteria-containing environment;

s6: and 7-14 days later, observing whether the culture mediums on the lower surface of the inert material and the lower surface have colonies or not and counting the colonies.

Control group:

consistent with the test procedures of the test group, except that instead of forming an antimicrobial occlusive composite on the top surface of the inert material, a layer of antimicrobial solution of the same type and concentration as the first composition solution forming the wound occlusive composite was sprayed.

(3) The antibacterial closed composite material can be formed on the surface of a wound of a pig anorectum or the perianal wound of the pig in situ for a certain period of time.

The test method comprises a test 1 and a test 2:

test 1:

s1: weighing 100g of the first composition solution by using a 200mL beaker, and rapidly stirring the first composition solution by using a magnetic stirrer (the rotating speed is 200-400 rpm) to form an obvious vortex;

s2: weighing 25g of the second composition solution by using a 100mL beaker, quickly pouring into the first composition solution at one time, and timing by using an immediate stopwatch;

s3: when a fixed antibacterial closed composite material is formed in the beaker, timing and recording the time for forming the glue, wherein the judgment standard for forming the fixed antibacterial closed composite material is as follows: the vortex of the solution in the beaker disappears, the mixed solution does not rotate along with the stirring, or the magnetic stirrer is obviously prevented from rotating or loses the stirring and mixing effect on the mixed system, namely the timing end point.

Remarking: because the antimicrobial closed composite is formed in a short time, the second composition solution should be added to the first composition solution at the same time as the first composition solution is being timed accurately.

Test 2:

s1: cutting a pig anorectum or perianal of a pig with the diameter of about 4cm, rubbing the pig anorectum or perianal of the pig by using abrasive paper to generate a wound surface, and smearing or spraying a thin layer of first composition solution on the wound surface;

s2: smearing or spraying a thin layer of second composition solution on the pig anorectal or the wound around the pig anus, and using a stopwatch to time;

s3: and (3) hanging and turning the wound surface of the pig anus intestine or the pig anus periphery by 180 ℃ while spraying the second composition, and observing whether an obvious antibacterial closed composite material layer is formed on the wound surface of the pig anus intestine or the pig anus periphery, wherein the antibacterial closed composite material does not flow and has a fixed shape. And (4) judging the standard: the antibacterial closed composite material layer does not flow, and the shape is fixed, which indicates that the gelling time of the first composition solution and the second composition solution is less than or equal to 1 s.

(4) The anti-displacement and anti-wrinkle test method of the antibacterial closed composite material on the wound surface of the pig anorectum or the pig perianal comprises the following steps:

s1: shearing pig anorectum or pig perianal with the length and width of about 6cm x 3cm, rubbing the pig anorectum or the pig perianal with abrasive paper to generate a wound surface, and smearing or spraying a first composition solution thin layer on the wound surface;

s2: smearing or spraying a layer of second composition solution on the pig anorectal or the wound surface around the pig anus to form an antibacterial closed composite material in situ;

s3: the pig anorectal wound or the pig perianal wound is horizontally placed, appropriate force is simultaneously applied to the edges of the two ends in the length direction, the pig anorectal wound or the pig perianal wound forms wrinkles, the force is removed after about 10 seconds, and the pig anorectal wound or the pig perianal wound recovers the stretched state. After repeating the folding-unfolding process for 10 times, observing the state of the antibacterial closed composite material on the wound surface of the pig anorectum or the pig perianal area, comprising the following steps: whether the displacement occurs or not, whether the antibacterial closed composite material falls off or not and whether the falling proportion exists or not.

Example 14-1

S1: preparation of a first composition solution: didecyl dimethyl ammonium Bromide, G2-8NH of example 7₂Branched polylysine-bonded carboxymethyl aminodextran, G2-8NH of example 9₂The branched polylysine bonded branched polydextrose is dissolved in a phosphate buffer (the pH value of the phosphate buffer is 5.0) to form a first composition solution with the mass content of 0.03%, 1.0% and 1.0% respectively;

s2: preparation of a second composition solution: the oxidized branched polydextrose of example 13 and the maleimide-terminated eight-arm polyethylene glycol of example 10 were dissolved in a phosphate buffer (pH 5.0) to form second composition solutions having mass contents of 1.2% and 0.8%, respectively;

s3: the pig anorectum or the pig perianal with the diameter of about 4cm is cut, and the ground surface is generated by rubbing the pig anorectum or the pig perianal with abrasive paper.

S4: the first composition solution is uniformly coated or sprayed with a thin layer on the wound surface of the pig anorectum or the pig perianal area, and then the second composition solution is uniformly coated or sprayed on the wound surface of the pig anorectum or the pig perianal area, so that the antibacterial closed composite material is rapidly formed on the wound surface of the pig anorectum or the pig perianal area in situ by the first composition and the second composition.

The sealing performance, the antibacterial property, the in-situ forming performance, the forming time, the displacement resistance and the wrinkle resistance of the antibacterial sealing composite material to the wound surface of the pig anorectum or the pig perianal are tested according to the test method.

Remarking: the concentrations of the first composition solution and the second composition solution of S1 and S2 indicated contents do not include lactose and mannitol which are excipients for lyophilization.

Example 14-2

S1: of solutions of the first compositionPreparation: benzachlor, G2-8NH of example 7₂Branched polylysine-bonded carboxymethyl aminodextran, G2-8NH of example 9₂The branched polylysine bonded branched polydextrose is dissolved in a phosphate buffer (the pH value of the phosphate buffer is 4.6) to form a first composition solution with the mass content of 0.06%, 1.5% and 1.0% respectively;

s2: preparation of a second composition solution: the oxidized branched polydextrose of example 13 and the succinimidyl group capped octa-arm polyethylene glycol carboxylic acid of example 11 were dissolved in a phosphate buffer (pH 4.6) to form a second composition solution having a mass content of 1.5% and 1.0%, respectively;

s3: cutting a pig anorectum or a pig perianal with the diameter of about 4cm, and rubbing the pig anorectum or the pig perianal with abrasive paper to generate a wound surface;

The sealing performance, the antibacterial resistance, the in-situ formation performance, the formation time, the displacement resistance and the wrinkle resistance of the antibacterial sealing composite material to the wound surface of the pig anorectum or the pig perianal are tested according to the test method.

Examples 14 to 3

S1: preparation of a first composition solution: chlorhexidine glucose, benzalkonium chloride, G3-16NH from example 8₂Branched polylysine-bonded carboxymethyl aminodextran, G2-8NH of example 9₂Dissolving branched polylysine bonded branched polydextrose in phosphate buffer (pH of phosphate buffer is 4.8) to form first composition solution with mass content of 0.03%, 1.2% and 1.0%;

s2: preparation of a second composition solution: the maleimide-terminated branched polydextrose of example 12, and the maleimide-terminated eight-arm polyethylene glycol of example 10 were dissolved in a phosphate buffer (pH of 4.8) to form second composition solutions having mass contents of 1.0% and 1.0%, respectively;

Examples 14 to 4

S1: preparation of a first composition solution: chlorhexidine acetate, benzalkonium bromide, G3-16NH of example 8₂Branched polylysine-bonded carboxymethyl aminodextran, G2-8NH of example 9₂Dissolving branched polylysine bonded branched polydextrose in phosphate buffer (pH of phosphate buffer is 4.6) to form first composition solution with mass content of 0.04%, 1.0% and 1.2%;

s2: preparation of a second composition solution: preparation of maleimide-terminated branched polydextrose example 12, example 11 succinimidyl-terminated eight-arm polyethylene glycol carboxylic acid was dissolved in phosphate buffer (pH 4.6 of phosphate buffer) to form second composition solutions with a mass content of 0.8% and 1.0%, respectively;

The sealing performance, antibacterial resistance, in-situ formation performance and formation time, and the displacement resistance and wrinkle resistance test results of 4 different antibacterial sealing composite materials on the pig anorectal or pig perianal wound surfaces are shown in the following tables 1, 2, 3 and 4.

TABLE 1 closure of the antibacterial closure composite to the porcine anorectal or perianal wound of a pig

Examples	Hydrostatic pressure	Time	Sealing property
				14-1	520mm	300s	Without leakage
14-2	525mm	300s	Without leakage
				14-3	515mm	300s	Without leakage
14-4	525mm	300s	Without leakage

As shown in table 1, the results of the sealing test on the wound surface around the pig anorectum or the pig anus by the antibacterial sealing composite material show that 4 different antibacterial sealing composite materials in examples 14-1 to 14-4 are applied or sprayed on the wound surface around the pig anorectum or the pig anus, and form a water pressure of about 500mm on the wound surface around the pig anorectum or the pig anus, and no water leakage is found, which indicates that the antibacterial sealing composite material of the present invention has good sealing performance on the wound surface around the pig anorectum or the pig anus.

TABLE 2 antibacterial and bacteriostatic Properties of antibacterial closed composites

As shown in the results of the antibacterial activity test of the antibacterial closed composite material in table 2, the 4 different antibacterial closed composite materials in examples 14-1 to 14-4 have no bacteria in the test process, which indicates that the antibacterial closed composite materials all have good antibacterial activity, and the control group has poor antibacterial activity and the number of colonies in the culture medium is significantly greater than that of the test group because the wound surface closed composite material is not used.

TABLE 3 in situ formation and formation time of antimicrobial occlusive composite material on porcine anorectal or perianal wound

Examples	Whether or not to form in situ	In-situ gel forming time
			14-1	Is that	≤1s
14-2	Is that	≤1s
			14-3	Is that	≤1s
14-4	Is that	≤1s

As shown in table 3, the data table of the in situ formation property and in situ formation time of the antibacterial closed composite material on the wound surface of the pig anorectum or the pig perianal area shows that 4 different antibacterial closed composite materials in examples 14-1 to 14-4 are coated or sprayed on the wound surface of the pig anorectum or the pig perianal area, 4 different antibacterial closed composite material layers can be formed in situ on the wound surface of the pig anorectum or the pig perianal area, and the formation time is less than or equal to 1 s.

TABLE 4 anti-migration and anti-wrinkle test results of antibacterial closed composite on the wound surface of pig anorectum or pig perianal

As shown in table 4, the results of the anti-displacement and anti-wrinkle tests on the wound surface of the pig anorectum or the pig perianal area of the antibacterial closed composite material in examples 14-1 to 14-4 show that 4 different antibacterial closed composite materials in examples 14-1 to 14-4 are coated or sprayed on the wound surface of the pig anorectum or the pig perianal area of the pig, and after a plurality of wrinkle tests, the results show that the 4 different antibacterial closed composite materials have good anti-displacement and anti-wrinkle properties on the wound surface of the pig anorectum or the pig perianal area of the pig.

Example 15

Application of antibacterial sealing composite material to wound surface after anorectal surgery

The anorectal surgery, in particular to the related surgery such as external hemorrhoid, internal hemorrhoid, mixed hemorrhoid, anal fistula, perianal abscess and the like, has the following characteristics similar to clinical data: the traditional Chinese medicine composition has the advantages of high morbidity, obvious symptoms, more complications such as postoperative pain and edema, secondary trauma caused by adhesion after dressing change, long dressing change time, strong recurrence and infection, long hospitalization time, strong influence on living and living property, and cannot be solved at present.

Clinical application process and comparison:

(1) test groups:

s1: preparation of a first composition solution: benzalkonium chloride, didecyldimethylammonium bromide, G2-8NH from example 7₂Branched polylysine-bonded carboxymethyl aminodextran, G2-8NH of example 9₂The branched polylysine bonded branched polydextrose is dissolved in phosphate buffer (pH of phosphate buffer is 4.5) to form first composition solutions with mass contents of 0.05%, 0.025%, 1.5% and 1.0%, respectively;

s2: preparation of a second composition solution: example 13 preparation of Oxycoramic polydextrose, example 11 succinimidyl group capped eight-arm polyethylene glycol carboxylic acid was dissolved in phosphate buffer (pH 4.5 of phosphate buffer) to form a second composition solution with a mass content of 1.0% and 0.8%, respectively;

S3: after the hemorrhoid operation wound surface is debrided (the wound surface situation after debridement is recorded as shown in fig. 14 (1)), the S1 first component solution is uniformly coated or sprayed with a thin layer on the debrided operation wound surface, and then the S2 second component solution is uniformly covered on the debrided operation wound surface, so that an antibacterial sealing composite material is quickly formed on the wound surface in situ, and the wound surface is sealed, isolated and protected.

S4: after 7-14 days of operation, the wound healing status after operation was observed, and the results are shown in fig. 14 (2).

(2) Control group:

patients were not treated with the antimicrobial occlusive composite of the present invention and were cared for according to conventional post-operative treatment methods.

The clinical application results are as follows:

fig. 14(1) shows the condition of the wound surface after debridement of the hemorrhoid surgical wound surface of the patient, as shown in fig. 14(1), it can be seen that the postoperative wound surface is larger, deeper, bare, has no outer layer skin-like protective tissue, the wound surface still has blood seepage, and the extrusion stimulation formed between the wound surface and the wound surface after the anal orifice is closed is inevitable. Under the condition and environment of the wound surface, if the wound surface is not properly and effectively protected, obvious pain, inflammation, infection, tissue adhesion and the like after operation are inevitably caused, bleeding, body temperature rise, immunity decline and swelling can occur, discomfort in daily life is also inevitably caused, the healing time is long, the hospitalization time is long, the times of repeated hospital diagnosis and treatment are increased, the cost is greatly increased, and the like.

Fig. 14(2) is a schematic view of the wound surface of a patient 7 days after the operation using the antibacterial sealing composite material of the present invention after the hemorrhoid surgical wound surface is debrided, and fig. 14(2) is a schematic view of the wound surface of the patient 7 days after the operation using the antibacterial sealing composite material of the present invention after the hemorrhoid surgical wound surface is debrided, a layer of the antibacterial sealing composite material of the present invention is formed in situ on the wound surface, the wound surface is protected by in situ sealing, and the wound surface condition is observed when the patient is discharged from the hospital on day 4 and the hospital is rechecked on day 7. As shown in fig. 14(2), the surface of the wound surface has no adhesion with other tissues, and the surface of the wound surface has obvious and complete self-protective skin-like tissue growth of human body, which indicates that the wound surface of the patient has been well healed 7 days after the operation. Inquiring physical experience and complications of the patient after the postoperative wound surface is healed within 7 days, and displaying the result: the wound surface of a patient has certain pain, slight inflammation and slight swelling within 4 days after operation, and no adhesion, secondary dressing wound and blood seepage are generated in the dressing change process on the 3 rd day and the 7 th day.

Fig. 14(3) is a schematic view of the wound surface of a patient 12 days after the hemorrhoid surgical wound surface is debrided without using the antibacterial sealing composite material of the present invention, and fig. 14(3) is a schematic view of the wound surface of the patient 12 days after the hemorrhoid surgical wound surface is debrided without using the antibacterial sealing composite material of the present invention, and the wound surface is obtained by adopting the traditional medical care mode, discharging from hospital on day 7 and the hospital for re-visit on day 12. As shown in fig. 14(3), there is still some oozing blood on the surface of the wound, and there is no obvious and relatively intact skin tissue growth on the surface of the wound, which indicates that the wound still has no obvious healing after 12 days of operation. Inquiring physical experience and complications of the patient after the postoperative wound surface is healed within 7 days, and displaying the result: the wound surface of a patient has obvious pain feeling, inflammation and swelling within 7 days after operation, and has obvious blood seepage due to adhesion generation and secondary dressing wound in the dressing change processes on days 3 and 7. Still has obvious painful thrill sensation on the 12 th day after the operation, needs auxiliary oral medicines and influences living.

And (3) displaying comprehensive results: the healing effect of the postoperative wound of a patient in a test group is obviously better than that of a patient in a control group, and the comparison result shows that the antibacterial closed composite material has obvious superiority.

While the principles of the invention have been described in detail in connection with the preferred embodiments thereof, it will be understood by those skilled in the art that the foregoing embodiments are merely illustrative of exemplary implementations of the invention and are not limiting of the scope of the invention. The details of the embodiments are not to be interpreted as limiting the scope of the invention, and any obvious changes, such as equivalent alterations, simple substitutions and the like, based on the technical solution of the invention, can be interpreted without departing from the spirit and scope of the invention.

Claims

1. An antibacterial occlusive composite material for application to a wound surface of anorectal surgery, comprising a first composition and a second composition, wherein the first composition comprises a primary amino-terminated branched polylysine bonded carboxymethyl aminodextran, a primary amino-terminated branched polylysine bonded branched polydextrose, and an antibacterial agent, and the second composition is a modified branched polydextrose multi-site cross-linking agent and a maleimide-terminated eight-arm polyethylene glycol cross-linking agent, or a modified branched polydextrose multi-site cross-linking agent and a succinimide-group-terminated eight-arm polyethylene glycol cross-linking agent;

the primary amino-terminated branched polylysine bonded to the carboxymethyl aminodextran is formed by bonding the primary amino-terminated branched polylysine to the carboxymethyl aminodextran through an amide bond, wherein the number of the branched polylysine molecules bonded to each carboxymethyl aminodextran macromolecule is at least 25, the primary amino-terminated branched polylysine has 8 or 16 branches, and each branch has only one primary amino group at the end;

the branched polylysine bonded to the branched polydextrose, which is blocked by primary amino groups, is formed by bonding the branched polylysine and the branched polydextrose through an amide bond, wherein the number of the branched polylysine molecules bonded to each branched polydextrose polymer is at least 15, and the branched polylysine bonded to the primary amino groups has 8 or 16 branched chains, and each branched chain has only one primary amino group at the end.

2. An antimicrobial occlusive composite material for application over an anorectal surgical wound surface according to claim 1 wherein said antimicrobial agent comprises at least one of didecyldimethyl ammonium chloride, didecyldimethyl ammonium bromide, chlorhexidine acetate, chlorhexidine gluconate, benzalkonium chloride, peroxyacetic acid, benzalkonium bromide and dibromohydantoin.

3. An antimicrobial occlusive composite material for application to a surgical wound surface in anorectal surgery according to claim 1 wherein said carboxymethyl aminodextran has an average molecular weight of 200000 daltons or more.

4. An antibacterial occlusive composite material for anorectal surgical wounds according to claim 3, wherein said carboxymethyl aminodextran has a degree of carboxymethyl substitution of 0.75 or more.

5. The antibacterial sealing composite material applied to the wound surface of anorectal surgery, wherein the branched polyglucose multi-site cross-linking agent comprises one active group selected from aldehyde group, acrylate group, succinimide ester group and maleimide group.

6. A method for preparing an antibacterial sealing composite material for anorectal surgical operation wounds according to any one of claims 1 to 5, wherein the method comprises the following steps:

s2: dissolving a first composition in the first composition buffer solution to obtain a first composition solution;

7. The method for preparing the antibacterial composite sealing material for anorectal surgical operation wound surface according to claim 6, wherein the anti-inflammatory agent comprises at least one of ibuprofen, diclofenac, naproxen sodium, metronidazole, tinidazole, ornidazole, aspirin, acetaminophen and indometacin piroxicam.

8. The method for preparing an antibacterial sealing composite material for anorectal surgical operation wound surface according to claim 6, wherein the antibiotic comprises at least one of cefaclor, ceftazidime, cefdinir, cephalexin, erythromycin, ciprofloxacin, ofloxacin, mupirocin, fusidic acid, cortisone, hydrocortisone, and dexamethasone.

9. The method of claim 6, wherein the primary amino-terminated branched polylysine-bonded carboxymethyl aminodextran and the primary amino-terminated branched polylysine-bonded branched polyglucose in the first composition solution are present in concentrations of 0.8% to 3.0% and 0.5% to 2.0% by mass, respectively, and the total concentration by mass of the two is no more than 4.0%.