Traditional Chinese medicine hydrogel composition for preventing and treating anorectal postoperative wound infection as well as preparation method and application of traditional Chinese medicine hydrogel composition

Abstract

The invention discloses a traditional Chinese medicine hydrogel composition for preventing and treating anorectal postoperative wound infection as well as a preparation method and application of the traditional Chinese medicine hydrogel composition. Based on traditional Chinese medicine classical ointment powder and in combination with clinical experience, chemical cutting optimization is performed to form a traditional Chinese medicine compound preparation, and the traditional Chinese medicine compound preparation is wrapped by taking a high polymer material as a skeleton and taking glycerol as a wrapping agent; and a stable temperature-sensitive in-situ hydrogel administration system is formed, so that the combination of the traditional Chinese medicine preparation and the hydrogel is realized, and the problems of the traditional ointment are effectively solved. The traditional Chinese medicine hydrogel composition directly acts on a wound surface, is good in adhesiveness and histocompatibility, and can prolong the residence time of a medicine at a medication part and improve the bioavailability; the active ingredients of the traditional Chinese medicine compound preparation can prevent the formation of bacterial biofilm on the wound surface after anorectal operation and inhibit wound surface infection; the hydrogel dosage form enables the hydrogel to form a moist protective film on a postoperative wound surface and form a microenvironment beneficial to wound surface healing, so that healing is accelerated, rehabilitation is promoted, the pain of a patient is effectively relieved, and the hydrogel has important medical value.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery, and a preparation method and application thereof. Background Art

[0002] Anorectal surgery refers to surgical procedures involving the anus and rectum, which are used to treat various anorectal diseases. Anorectal surgery often uses open drainage incisions, and wound exposure and defecation contamination are inevitable, which affects wound healing. Clinical studies have shown that wound infection is an independent risk factor for poor wound healing after anorectal surgery. Improper treatment can easily cause delayed wound healing, or even non-healing or pseudo-healing and scar contracture, leading to prolonged course of disease or recurrence. According to literature reports, the recurrence rate after anorectal surgery can be as high as 57%, causing patients to prolong the course of the disease and seek medical treatment repeatedly, aggravating the pain of patients, delaying their ability to work and live, increasing the mental stress of patients, reducing the quality of life, and also causing great waste of medical and health resources. Therefore, the repair and healing of postoperative wounds is the last link in determining the prognosis of anorectal diseases, and the quality of healing directly affects the course of disease, efficacy and prognosis.

[0003] The key is to prevent and control bacterial contamination of open wounds. Studies have confirmed that postoperative open drainage incision wound infection is mainly caused by bacterial contamination. Bacterial colonization and growth to form bacterial biofilms and changes in the wound microenvironment are important causes of wound healing disorders. Bacterial biofilms can form an immune barrier, which is conducive to bacterial gene mutation and exchange of drug-resistant genes, and can strengthen bacterial adhesion to wounds, enhance coordination between bacterial communities, and facilitate the dormancy of retained bacteria. Therefore, conventional debridement methods are difficult to effectively remove bacterial biofilms from wounds, resulting in prolonged healing of infected wounds.

[0004] In clinical practice, antibiotics are often used as antibacterial drugs to fight infection. However, antibiotics are very easy to develop drug resistance, especially the biofilm barrier formed by drug-resistant bacteria caused by the abuse of antibiotics is more difficult to remove, and it is also more likely to cause dysbiosis, which further worsens the condition. Traditional Chinese medicine is mostly natural ingredients, with low prices and mild toxic side effects. Thousands of years of clinical practice have confirmed that traditional Chinese medicine has the advantages of simple, cheap, green and natural treatment for anti-infection. For example, the classic prescriptions of traditional Chinese medicine surgery recorded in the "Medical Mirror" are widely used in the prevention and treatment of various infectious diseases, with significant efficacy, and can be called the "holy medicine" of traditional Chinese medicine surgery. However, the classic prescriptions of traditional Chinese medicine surgery or the existing prescriptions based on them all use Coptis chinensis as the main ingredient, and there are many different compatibility flavors. Coptis chinensis is cold in nature and bitter in taste. It enters the heart, liver, stomach, and large intestine meridians. Its effects are: clearing away heat and dampness, purging fire and detoxifying. Although Coptis chinensis has a certain antibacterial effect and has a strong inhibitory effect on Gram-positive bacteria, for anorectal surgery, the wound exposure environment is complex and faces more bacterial infections. Therefore, the existing classic Coptis chinensis ointment formula is not ideal for the inhibitory effect on the formation of bacterial biofilms in anorectal surgery.

[0005] Moreover, the existing Chinese medicine prescriptions for preventing and treating postoperative wound infection of anorectal rectum are mostly ointments or creams. For example, the pharmaceutical composition for promoting wound healing after anorectal rectum surgery disclosed in Chinese patent application CN112972368A is prepared into a cream preparation using drug-loaded microemulsion, drug-loaded microspheres, stem cell exosome liposomes and gel; wherein the drug-loaded microemulsion is a W / O type emulsion, which is composed of an aqueous phase, an oil phase and an emulsifier with a mass ratio of 2 to 3:6 to 7:1, and the oil phase is one of jojoba oil, sesame oil, olive oil or sweet almond oil. The presence of the oil phase leads to oil stains in these preparations, which not only makes debridement difficult and increases the pain of the dressing change process, but also easily provides a favorable environment for the formation of bacterial biofilms due to inadequate debridement, increasing the probability of repeated wound infection and the longer healing time.

[0006] Hydrogel is a special drug preparation that can absorb and retain a large amount of water, promote wound healing, and relieve postoperative symptoms such as pain and edema. For example, Chinese patent document CN110624054B discloses a Chinese medicine compound hydrogel for treating skin wound healing, and its preparation method and application, wherein a multi-component Chinese medicine and a carbomer matrix are formulated into a hydrogel for treating skin wounds, improving the tissue pathology of damaged skin, and promoting wound healing of mechanically damaged skin. However, although carbomer is a synthetic high molecular polymer with good biocompatibility, its biodegradability is poor and there is a risk of allergies for some sensitive people. Most importantly, carbomer contains a large number of carboxylic acid groups and is acidic (pH 2.5-3.0). When it is used as a gel skeleton, it is necessary to use an additional pH adjuster to adjust the drug to a suitable pH value. This not only complicates the drug composition, but the commonly used pH adjusters, such as triethanolamine, have a certain alkalinity. If used improperly, it is easy to cause inappropriate drug pH to irritate the wound and increase the difficulty of healing. In addition, ingredients such as triethanolamine may also interact with certain traditional Chinese medicine ingredients, affecting the overall stability of the preparation.

[0007] In addition, the care of wounds after anorectal surgery not only has the particularity of repeated contamination, but also for deep wounds such as complex anal fistulas and perianal abscesses, most of the existing hydrogels lack sufficient mechanical stability and cannot maintain a complete structure in deep wounds, which is not conducive to drug application and shaping, and it is difficult to accurately adapt to the shape and size of the wound, as well as fill fistulas and dead spaces. Most importantly, the form of Chinese medicine ingredients directly determines the therapeutic effect, and the decoction of Chinese medicine ingredients is generally a solution. The existing hydrogels are difficult to stably wrap the liquid Chinese medicine, and the liquid medicine is released too quickly during use, and the effect of long-term antibacterial repair cannot be achieved.

[0008] Therefore, developing a traditional Chinese medicine hydrogel suitable for postoperative wound infection in anorectal surgery remains an urgent problem to be solved. Summary of the invention

[0009] In view of the above-mentioned problems that the existing oily ointment dosage forms have difficulties in wound debridement and poor inhibitory effect on bacterial biofilm formation; the use of carbomer and the like as the matrix to prepare hydrogels has the problem of pH irritation to the wound and the pH adjuster may interact with some Chinese medicine ingredients, and the drug encapsulation is poor and cannot be shaped for long-term antibacterial. The present invention provides a Chinese medicine hydrogel composition for preventing and treating postoperative anorectal wound infection and its preparation method and application. On the basis of the classic prescriptions of traditional Chinese medicine surgery, combined with clinical experience, secondary innovation, reasonable combination of monarch, minister, adjuvant and guiding drugs, and tailor-made Chinese medicine compound prescriptions, effectively achieve the purpose of blocking the formation of bacterial biofilm on the wound and promoting the repair of postoperative anorectal wounds; at the same time, it is supplemented with natural polymer materials to prepare hydrogel dressing dosage forms, which solves the problem of difficult debridement of oily ointment dosage forms and promotes the efficacy of Chinese medicine drugs, and is conducive to drug perfusion of deep wounds such as high-level complex anal fistulas and perianal abscesses. The specific technical scheme is as follows:

[0010] First, the present invention provides a traditional Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery, the composition is composed of a traditional Chinese medicine compound and a hydrogel matrix, and the traditional Chinese medicine compound is composed of the following 12 herbs:

[0011] Main medicine: Coptis chinensis, Scutellaria baicalensis,

[0012] Ministerial drugs: Forsythia suspensa, Phellodendron chinense, Rhubarb,

[0013] Auxiliary drugs: turmeric, angelica, raw earth, lithospermum officinale, sophora flavescens, purslane,

[0014] Adjuvant: borneol;

[0015] The hydrogel matrix includes a gel skeleton and an encapsulating agent;

[0016] The gel skeleton is a natural hydrogel polymer material;

[0017] The encapsulating agent is glycerol, and its usage is 8-10% of the total mass of the hydrogel matrix.

[0018] The aforementioned traditional Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery, the 12 herbs in the traditional Chinese medicine compound, by weight, are: 12-36 parts of coptis chinensis, 12-36 parts of scutellaria baicalensis, 12-36 parts of phellodendron chinense, 12-36 parts of turmeric, 9-27 parts of rhubarb, 12-36 parts of forsythia suspensa, 12-36 parts of sophora flavescens, 18-54 parts of angelica sinensis, 36-108 parts of rehmannia glutinosa, 12-36 parts of purslane, 9-27 parts of lithospermum officinale, and 2-6 parts of borneol.

[0019] Preferably, in the aforementioned traditional Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery, the 12 herbs in the traditional Chinese medicine compound are, by weight, 12 parts of coptis chinensis, 12 parts of scutellaria baicalensis, 12 parts of phellodendron chinense, 12 parts of turmeric, 9 parts of rhubarb, 12 parts of forsythia suspensa, 12 parts of sophora flavescens, 18 parts of angelica sinensis, 36 parts of rehmannia glutinosa, 12 parts of purslane, 9 parts of lithospermum officinale, and 2 parts of borneol.

[0020] The aforementioned traditional Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery, the gel skeleton of the hydrogel matrix is ​​any one or a combination of hyaluronic acid, alginate, water-soluble chitosan, cellulose, gelatin, agarose, silk protein, collagen; preferably a combination of hyaluronic acid and water-soluble chitosan; the mass ratio of hyaluronic acid to water-soluble chitosan is 2-4:3-5, preferably 3:4.

[0021] In the aforementioned traditional Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery, the hyaluronic acid is non-cross-linked sodium hyaluronate with a molecular weight of 1 million to 1.8 million Da; the water-soluble chitosan is carboxymethyl chitosan with a molecular weight of 150 to 250 kDa and a degree of substitution of 35 to 45%.

[0022] Secondly, the present invention provides a method for preparing the aforementioned traditional Chinese medicine hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery, comprising the following steps:

[0023] 1) Extraction and preparation of concentrated Chinese medicine liquid: quantitatively weigh the raw materials of the Chinese medicine compound, except for borneol, wash the remaining raw materials with water, decoct and concentrate, and finally add borneol to prepare a concentrated Chinese medicine liquid;

[0024] 2) preparing a hydrogel skeleton: quantitatively weighing a gel skeleton of a hydrogel matrix, dissolving it in an appropriate amount of water, and preparing a hydrogel skeleton;

[0025] 3) Drug loading: adding the concentrated Chinese medicine solution prepared in step 1) to the hydrogel skeleton prepared in step 2) while hot, and stirring to disperse the drug in the gaps of the hydrogel skeleton to form a hydrogel drug loading system;

[0026] 4) Oil encapsulation: Add glycerol and stir at an appropriate speed to form an oil film on the gaps of the hydrogel skeleton, encapsulate the concentrated Chinese medicine liquid in the gaps of the hydrogel skeleton, form a stable temperature-sensitive in situ hydrogel drug delivery system, and cool to room temperature to obtain a Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery.

[0027] As a preferred technical solution, in step 1), the specific process of extracting and preparing concentrated Chinese medicine solution is:

[0028] Weigh the raw materials of the Chinese medicine compound quantitatively, except for borneol, and wash the remaining raw materials with water;

[0029] Soak, add twice the amount of water, soak at room temperature for 30 minutes; start boiling:

[0030] First decoction, add 5 times the amount of water, simmer for 60 minutes, filter the original liquid, and set aside the filtrate;

[0031] Continue to decoct, add 4 times the amount of water, simmer for 45 minutes, filter the original solution, and set aside the filtrate;

[0032] Decoction again, add 3 times the amount of water, simmer for 30 minutes, filter the original liquid, and set aside the filtrate;

[0033] The three decoction filtrates were combined and concentrated at a constant temperature of 60°C to prepare a concentrated Chinese medicine stock solution with a concentration of 1 g / ml;

[0034] Then, ethanol is added until the ethanol content reaches 70%, the mixture is allowed to stand for 24 hours, filtered, and the filtrate is subjected to de-alcoholization by vacuum distillation at a constant temperature of 60°C to obtain a Chinese medicine compound alcohol precipitation concentrate;

[0035] Take the alcohol-precipitated concentrated solution of the Chinese medicine compound, add 4 times the amount of purified water, heat it in a 60°C water bath, filter the precipitate with absorbent cotton while it is still hot, concentrate it under reduced pressure, and then add borneol to obtain a concentrated Chinese medicine solution with a concentration of 1 g / ml.

[0036] As a preferred technical solution, in step 2), the specific process of preparing the hydrogel skeleton is: weigh non-cross-linked sodium hyaluronate and carboxymethyl chitosan according to the mass ratio, add them into distilled water respectively, and prepare 30 mg / mL sodium hyaluronate solution and 40 mg / mL carboxymethyl chitosan solution at 60°C; then slowly add the carboxymethyl chitosan solution into the sodium hyaluronate solution in a volume ratio of 1:1, and stir at a speed of 200 to 300 rpm to fully mix the two to obtain a hydrogel skeleton.

[0037] As a preferred technical solution, in step 3), the volume ratio of the concentrated Chinese medicine solution to the hydrogel skeleton for drug loading is 5 to 10:1; the temperature of the concentrated Chinese medicine solution is 60°C, and the stirring speed after adding the hydrogel skeleton is 200 to 300 rpm.

[0038] As a preferred technical solution, in step 4), in the oil-in-oil encapsulation, the hydrogel drug-carrying system is cooled to 35-40° C., glycerol is added, and the stirring speed of the encapsulation is controlled to 50-150 rpm.

[0039] In addition, the present invention also provides an application of the aforementioned traditional Chinese medicine hydrogel composition in the preparation of drugs for preventing and treating various anorectal surgical wound infections, including the preparation of drugs for preventing the formation of bacterial biofilms on various anorectal surgical wounds and promoting the healing of surgical wounds.

[0040] The innovative features and beneficial effects of the present invention are as follows:

[0041] 1) The Chinese medicine compound of the present invention is based on the classic paste powder of traditional Chinese medicine, combined with clinical experience, and further tailored and optimized. First, the Chinese medicine compound of the present invention uses coptis chinensis and scutellaria baicalensis as the main medicine, and the two have the same nature and flavor, and similar effects. The two are combined as the main medicine, which not only enhances the effects of clearing away heat and dampness, purging fire and detoxifying, but also the active ingredients in coptis chinensis and scutellaria baicalensis can work synergistically to inhibit the formation of bacterial biofilm. Among them, coptis chinensis has a strong inhibitory effect on gram-positive bacteria, while scutellaria baicalensis has a good inhibitory effect on gram-negative bacteria. The antibacterial spectrum of the two is complementary, covering different types of bacteria more comprehensively, and helping to inhibit the formation of bacterial biofilm on the wound surface. In addition, baicalein, an effective ingredient in scutellaria baicalensis, can interfere with bacterial signal molecules and prevent bacterial aggregation. Coptis chinensis can degrade bacterial endotoxins, destroy bacterial cells, and inhibit their growth. The combination of the two can more effectively inhibit bacterial colonization, reproduction and growth, effectively block bacterial infection and biofilm formation in wounds after anorectal surgery, and achieve inhibition of repeated infection of wounds and prevention of inflammatory reactions.

[0042] Secondly, the Chinese medicine compound of the present invention uses Phellodendron chinense, Rhubarb and Forsythia suspensa as the assistant medicines to assist the main medicines in strengthening the effects of clearing away heat and dampness, purging fire and detoxifying; at the same time, the three can also play the effects of promoting blood circulation, removing blood stasis, eliminating carbuncle and dispersing nodules, so as to improve the microcirculation of the wound surface, further prevent bacterial infection of the wound surface, reduce wound edema and pain, and promote healing.

[0043] Thirdly, the Chinese medicine compound of the present invention uses angelica, turmeric, raw rehmannia, lithospermum officinale, sophora flavescens, and purslane as adjuvants. The six medicinal materials assist the main and auxiliary medicines to further enhance the effects of clearing away heat, detoxifying, and drying dampness, while enhancing the effects of promoting qi and blood circulation, unblocking meridians and relieving pain. Among them, angelica and turmeric are warm in nature, and can assist in alleviating the disadvantages of the bitter and cold nature of various medicines, promote blood circulation, remove blood stasis, unblock meridians and relieve pain. Purslane and raw rehmannia nourish yin, nourish blood, promote new blood circulation, and promote healing.

[0044] Finally, the Chinese herbal compound of the present invention uses borneol as a guiding drug, taking advantage of its strong pungent aroma and its nature of moving but not staying, to lead the various drugs in the prescription directly to the site of the disease, and give full play to the efficacy of each medicinal flavor in the medicine, thereby achieving broad-spectrum antibacterial sterilization and effective inhibition of bacterial bioformation, while also being able to improve local microcirculation, accelerate metabolism, and promote the healing of wounds after anorectal surgery.

[0045] 2) The Chinese medicine hydrogel composition of the present invention not only effectively solves the problem of oil pollution of traditional Chinese medicine ointments and powders, but also has good formability, is easy to use, has a long-lasting effect, and is conducive to wound healing. Among them, the hydrogel matrix of the Chinese medicine hydrogel composition of the present invention uses natural hydrogel polymer materials as a skeleton, which not only has good biocompatibility and biodegradability, but also further ensures the safety of the drug; at the same time, the natural hydrogel skeleton has good adhesion and shaping ability, which is conducive to the use of drug infusion in deep wounds such as high-level complex anal fistulas and perianal abscesses.

[0046] In addition, the matrix skeleton formed by the natural hydrogel polymer material is a three-dimensional structure, which allows the concentrated Chinese medicine liquid to be evenly dispersed and wrapped in it, and then wrapped and encapsulated with glycerol to form a stable temperature-sensitive in-situ hydrogel drug delivery system. When used, the Chinese medicine hydrogel composition directly acts on the wound surface, slowly releases the Chinese medicine liquid through the influence of body temperature, prolongs the retention time of the drug at the medication site, and improves bioavailability.

[0047] 3) The Chinese medicine hydrogel composition of the present invention uses glycerol as an encapsulating agent, so that the concentrated Chinese medicine liquid can be stably encapsulated in the natural hydrogel matrix skeleton to prevent the loss of the medicine liquid; at the same time, the amount of glycerol is controlled to 8-10% of the total mass of the hydrogel matrix, which helps to maintain the stability of the three-dimensional network structure of the natural hydrogel matrix skeleton and the shaping ability of the gel composition, realize the controlled release of the drug, adapt to the long-term stable drug administration treatment of anorectal surgical wounds, and at the same time help to reduce the microbial load of the wound, reduce the susceptibility of bacterial colonization, promote the proliferation and migration of keratinocytes and fibroblasts, and further accelerate wound healing.

[0048] 4) The Chinese medicine hydrogel composition of the present invention is rich in active groups. The natural hydrogel polymer material can be combined with the components in the Chinese medicine to give it specific properties or drug sustained-release ability, which is beneficial to the sustained and stable release of the efficacy of the Chinese medicine compound and enhances the efficacy of the drug; the two work together to further help solve the problem of easy contamination, bacterial colonization and growth, and formation of bacterial biofilm in open drainage incisions after clinical anorectal surgery.

[0049] In particular, when the combination of hyaluronic acid and water-soluble chitosan is used as the gel skeleton, the hyaluronic acid molecule contains carboxyl and hydroxyl groups. The carboxyl group is negatively charged in aqueous solution and can be combined with the amino group (positively charged molecule) in the chitosan molecule through electrostatic interaction; the hydroxyl group participates in the formation of intermolecular hydrogen bonds and interacts with the carboxylmethyl group in the water-soluble chitosan, which helps to stabilize the hydrogel structure. At the same time, the combined gel skeleton of hyaluronic acid and water-soluble chitosan can interact with various chemical groups in traditional Chinese medicine ingredients through its active groups, thereby achieving effective drug delivery and controlled release. In the traditional Chinese medicine compound, coptis root, scutellaria root, forsythia root, phellodendron, rhubarb, etc. contain alkaloid components, which are usually alkaline and can interact electrostatically with the carboxyl groups in hyaluronic acid and water-soluble chitosan; turmeric, angelica root, raw rehmannia root, lithospermum officinale, sophora flavescens, etc. contain phenolic compounds, the hydroxyl groups of which can form hydrogen bonds with the carboxyl groups or amino groups in hyaluronic acid and water-soluble chitosan; purslane contains a variety of bioactive substances, including fatty acids, flavonoids, etc., which may bind to the hydrogel skeleton through hydrophobic effects or hydrogen bonds; and borneol is a monoterpene compound with hydrophobicity, which may interact with the hydrogel skeleton through hydrophobic effects. This can not only improve the bioavailability of drugs, but also optimize the release rate and therapeutic effect of drugs by adjusting the physicochemical properties of hydrogels.

[0050] Clinical applications have confirmed that the Chinese medicine hydrogel composition of the present invention has a direct effect on the local lesion, can effectively prevent the formation of bacterial biofilm on the anorectal wound surface, and exerts anti-inflammatory, analgesic, detumescent, blood circulation and myogenic effects, thereby inhibiting infection, relieving swelling, pain, bleeding, exudation and other symptoms, promoting recovery, and effectively alleviating the patient's pain, and has important medical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 This is a scanning electron microscope image (×2700) of the traditional Chinese medicine hydrogel composition prepared in Example 2 of the present invention;

[0052] Figure 2 The antibacterial results of product 1 (traditional Chinese medicine hydrogel composition) in Example 4 of the present invention on Escherichia coli;

[0053] Figure 3 The antibacterial results of product 2 (classic hydrogel group) in Example 4 of the present invention on Escherichia coli;

[0054] Figure 4 The antibacterial results of product 3 (classical prescription ointment) in Example 4 of the present invention on Escherichia coli;

[0055] Figure 5 The antibacterial results of product 1 (traditional Chinese medicine hydrogel composition) in Example 4 of the present invention on Staphylococcus aureus;

[0056] Figure 6 The antibacterial results of product 2 (classic hydrogel group) in Example 4 of the present invention on Staphylococcus aureus

[0057] Figure 7 The antibacterial results of product 3 (classic prescription ointment) in Example 4 of the present invention on Staphylococcus aureus;

[0058] Figure 8 The wound healing conditions of rats on the 3rd, 7th and 14th days of treatment in Example 5 of the present invention;

[0059] Fig. 9 The results of the inhibition of bacterial biofilm by the traditional Chinese medicine hydrogel composition in Example 5 of the present invention;

[0060] Fig.10 The results of the inhibition of bacterial biofilm by the classic ointment in Example 5 of the present invention are as follows;

[0061] Fig.11 This is a pathological section of the infected wound of the rat animal model in Example 5 of the present invention;

[0062] Fig.12 The wound surface treated with the classic prescription ointment in Example 5 of the present invention;

[0063] Fig.13 The wound surface treated with the classic hydrogel in Example 5 of the present invention;

[0064] Fig.14 The wound surface treated with the hydrogel of the present invention in Example 5 of the present invention;

[0065] Fig.15 These are photos of the infected wounds of clinical patients after anorectal surgery before and after treatment in Example 8 of the present invention;

[0066] Fig.16 The bacterial smear of the wound surface of the patient after anorectal surgery in Example 8 of the present invention;

[0067] Fig.17 These are the pathological sections before and after the infected wound after anorectal surgery of the patient in Example 8 of the present invention. DETAILED DESCRIPTION

[0068] In order to make the purpose, technical solution and advantages of the present invention more clear, the technical solution of the present invention will be clearly and completely described below in conjunction with embodiments.

[0069] Example 1

[0070] This embodiment is aimed at the problems that most traditional Chinese medicine prescriptions are ointments or creams, which have the disadvantages of oil stains and poor formability, and the hydrogel prepared with carbomer matrix is ​​not suitable for wound repair after anorectal surgery. A Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery and its preparation method and application are proposed. Based on the classic paste powder of traditional Chinese medicine, combined with clinical experience, it is optimized to form a Chinese medicine compound, using natural hydrogel polymer materials as the skeleton, and glycerol as the wrapping agent to wrap the concentrated liquid of the compound medicine therein to form a stable drug delivery system; thereby realizing the combination of Chinese medicine preparations and hydrogels, effectively solving the disadvantages of traditional paste powders such as oil stains, poor formability, and inconvenience in use, and the problems of easy contamination, bacterial colonization and growth, and formation of bacterial biofilm in open drainage incisions after clinical anorectal surgery.

[0071] The Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery in this embodiment is composed of a Chinese medicine compound and a hydrogel matrix. The Chinese medicine compound is based on the classic paste of traditional Chinese medicine, combined with clinical experience, and further modified and optimized. It is composed of the following 12 medicines: coptis root, scutellaria baicalensis, forsythia suspensa, phellodendron, rhubarb, turmeric, angelica, rehmannia root, lithospermum officinale, sophora flavescens, purslane, and borneol.

[0072] The Chinese medicine compound of the present embodiment, with coptis root and scutellaria root as the monarch medicine, the two have the same nature and flavor, similar efficacy, and the two are combined as the monarch medicine, not only enhancing the effect of clearing away heat and dampness, purging fire and detoxifying, but also the active ingredients in coptis root and scutellaria root can work synergistically to inhibit the formation of bacterial biofilm. Among them, coptis root has a strong inhibitory effect on gram-positive bacteria, while scutellaria root has a good inhibitory effect on gram-negative bacteria, and the antibacterial spectrum of the two has certain complementarity, so that the two can cover different types of bacteria more comprehensively when inhibiting wound bacteria; and the effective ingredient baicalin in scutellaria root can interfere with the signal molecules of bacteria, prevent the aggregation of bacteria, and the effective ingredient of coptis root can degrade the endotoxin of bacteria, destroy bacterial cells and inhibit the growth of bacteria. Therefore, the combination of the two can more effectively inhibit the formation of bacterial infection and biofilm of wound after anorectal surgery, inhibit inflammatory response, and can also improve local microcirculation, accelerate metabolism, and prevent and treat wound infection after anorectal surgery and promote wound healing.

[0073] Phellodendron chinense, rhubarb and forsythia suspensa are used as assistant drugs to assist the main drugs in strengthening the effects of clearing away heat and dampness, purging fire and detoxifying; at the same time, the three of them can also play the effects of promoting blood circulation, removing blood stasis, eliminating carbuncles and dispersing nodules, so as to improve the microcirculation of the wound, further prevent bacterial infection of the wound, reduce wound edema and pain, and promote healing.

[0074] With Chinese angelica, turmeric, raw rehmannia, lithospermum officinale, sophora flavescens and purslane as adjuvants, the six herbs assist the main and auxiliary herbs to further enhance the effects of clearing away heat, detoxifying and drying dampness, while enhancing the effects of promoting qi and blood circulation, unblocking meridians and relieving pain. Among them, Chinese angelica and turmeric are warm in nature, and can assist in alleviating the disadvantages of the bitter and cold nature of the other herbs, promoting blood circulation, removing blood stasis, unblocking meridians and relieving pain. Purslane and raw rehmannia nourish yin, nourish blood, promote new blood circulation and promote healing.

[0075] Borneol is used as a guiding drug, taking advantage of its strong pungent and fragrant smell and its moving and non-static nature, to lead the various drugs in the prescription directly to the site of the disease, and give full play to the efficacy of each medicinal flavor in the medicine, thereby achieving the effects of broad-spectrum antibacterial and sterilization, effectively inhibiting the formation of bacterial organisms, and promoting wound healing.

[0076] In this embodiment, the dosage of the 12 medicinal herbs in the Chinese medicine compound is respectively: 12-36 parts of coptis root, 12-36 parts of scutellaria root, 12-36 parts of phellodendron, 12-36 parts of turmeric, 9-27 parts of rhubarb, 12-36 parts of forsythia root, 12-36 parts of sophora flavescens, 18-54 parts of angelica, 36-108 parts of raw rehmannia root, 12-36 parts of purslane, 9-27 parts of lithospermum officinale, and 2-6 parts of borneol. The preferred formula is: 12 parts of coptis root, 12 parts of scutellaria root, 12 parts of phellodendron, 12 parts of turmeric, 9 parts of rhubarb, 12 parts of forsythia root, 12 parts of sophora flavescens, 18 parts of angelica, 36 parts of raw rehmannia root, 12 parts of purslane, 9 parts of lithospermum officinale, and 2 parts of borneol.

[0077] In this embodiment, the hydrogel matrix includes a gel skeleton and an encapsulating agent. Wherein, the gel skeleton is a natural hydrogel polymer material, including any one or a combination of hyaluronic acid, alginate, water-soluble chitosan, cellulose, gelatin, agarose, silk protein, and collagen; the encapsulating agent is glycerol. Natural hydrogel polymer materials not only have good biocompatibility and biodegradability, but also because the pH value of these materials is about 5-8, there is no need to use additional pH regulators, including triethanolamine, etc., to adjust the pH value, avoid the introduction of allergic components, simplify the pure product drug components, and further ensure the safety of the drug. In this embodiment, the natural hydrogel polymer material forms a matrix skeleton with a three-dimensional structure, and the concentrated Chinese medicine liquid prepared by the Chinese medicine compound is dispersed and encapsulated therein, and then encapsulated and packaged with glycerol, so that the drug-carrying system is stable, forming a stable temperature-sensitive in-situ hydrogel drug delivery system, which has a long-lasting effect and is easy to coat and clean, effectively solving the shortcomings of traditional pastes and powders such as oil pollution, poor formability, and inconvenience in use. At the same time, natural hydrogel polymer materials are rich in active groups and can be combined with components in traditional Chinese medicine to give them specific properties or drug sustained-release capabilities, which is conducive to the sustained and stable release of the efficacy of traditional Chinese medicine compound preparations and enhances the efficacy of drugs; the two work together to effectively solve the problems of easy contamination, bacterial colonization and growth, and bacterial biofilm formation in open drainage incisions after clinical anorectal surgery. For example, the combination of hyaluronic acid and water-soluble chitosan is used as the hydrogel matrix skeleton. The amino group (-NH2) in the water-soluble chitosan can be covalently cross-linked with the aldehyde group (-CHO) in the hyaluronic acid through the Schiff base reaction to form a stable hydrogel structure and enhance the mechanical strength and stability of the hydrogel. That is, the hyaluronic acid molecule contains carboxyl and hydroxyl groups. The carboxyl group is negatively charged in the aqueous solution and can be combined with the amino group (positively charged molecule) in the chitosan molecule through electrostatic interaction; the hydroxyl group participates in the formation of intermolecular hydrogen bonds and acts with the carboxylmethyl group in the water-soluble chitosan, which helps to stabilize the hydrogel structure. Moreover, the natural hydrogel polymer material can interact with various chemical groups in the Chinese medicine ingredients through its active groups, thereby achieving effective drug transport and controlled release. In this embodiment, the Chinese medicine compound contains alkaloid components such as coptis root, scutellaria baicalensis, forsythia suspensa, phellodendron chinense, rhubarb, etc., which are usually alkaline and can electrostatically interact with the carboxyl groups in hyaluronic acid and water-soluble chitosan; turmeric, angelica, raw rehmannia, lithospermum officinale, sophora flavescens, etc. contain phenolic compounds, whose hydroxyl groups can form hydrogen bonds with the carboxyl groups or amino groups in hyaluronic acid and water-soluble chitosan; purslane contains a variety of bioactive substances, including fatty acids, flavonoids, etc., which may be combined with the hydrogel skeleton through hydrophobic effects or hydrogen bonds; and borneol is a monoterpene compound with hydrophobicity, which may interact with the hydrogel skeleton through hydrophobic effects; thus, not only can the bioavailability of the drug be improved, but also the release rate and therapeutic effect of the drug can be optimized by adjusting the physicochemical properties of the hydrogel.

[0078] Studies have shown that due to anorectal surgical injuries and microvascular leakage, the pH value of the wound surface will increase, approaching the physiological pH value (7.4) that is conducive to bacterial infection. The hydrogel skeleton of the combination of hyaluronic acid and water-soluble chitosan, at a pH of about pH 7.4, the carboxyl portion of hyaluronic acid and the amino group bonding force in the chitosan molecule becomes weaker, and at the same time, the binding force with alkaloid components such as Coptis chinensis, Scutellaria baicalensis, Forsythia suspensa, Phellodendron amurense, and Rhubarb is weakened, which can change the gel structure, release drug ingredients, inhibit bacterial growth on the wound surface, reduce the microbial load on the skin surface, reduce susceptibility to bacterial colonization, and prevent bacteria from forming biofilms; at the same time, it creates a suitable pH environment for the proliferation and migration of keratinocytes and fibroblasts, and under the action of ingredients such as Angelica sinensis, Curcuma longa, Portulaca oleracea, and Rehmannia glutinosa, it nourishes yin and promotes wound healing.

[0079] In this embodiment, the mass ratio of the hyaluronic acid to the water-soluble chitosan is preferably 3:4, and the amount of glycerol used is 8-10% of the total mass of the hydrogel matrix, which can make the prepared traditional Chinese medicine hydrogel composition soft in texture, have a suitable porous structure to provide drug loading space, and have good water absorption and moisture retention, good gel shape-keeping ability and mechanical stability, so as to meet the needs of deep wounds such as anal fistulas and perianal abscesses with relatively high complexity, facilitate drug application and shaping, adapt to the shape and size of the wound, fill fistulas and dead spaces, and increase the application potential of traditional Chinese medicine hydrogel compositions.

[0080] In this embodiment, the preparation method of the traditional Chinese medicine hydrogel composition comprises the following steps:

[0081] 1) Extraction and preparation of concentrated Chinese medicine liquid: quantitatively weigh the raw materials of the Chinese medicine compound, except for borneol, wash with water, decoct and concentrate, and then add borneol to prepare a concentrated Chinese medicine liquid; the specific process is:

[0082] Weigh the raw materials of the Chinese medicine compound quantitatively, except for borneol, wash the remaining raw materials with water, add 2 times the amount of water, and soak at room temperature for 30 minutes;

[0083] First decoction, add 5 times the amount of water, simmer for 60 minutes, filter the original liquid, and set aside the filtrate;

[0084] Continue to decoct, add 4 times the amount of water, simmer for 45 minutes, filter the original solution, and set aside the filtrate;

[0085] Decoction again, add 3 times the amount of water, simmer for 30 minutes, filter the original liquid, and set aside the filtrate;

[0086] The three decoction filtrates were combined and concentrated at a constant temperature of 60°C to prepare a concentrated Chinese medicine stock solution with a concentration of 1 g / ml;

[0087] Then, ethanol is added until the ethanol content reaches 70%, the mixture is allowed to stand for 24 hours, filtered, and the filtrate is subjected to de-alcoholization by vacuum distillation at a constant temperature of 60°C to obtain a Chinese medicine compound alcohol precipitation concentrate;

[0088] Take the alcohol-precipitated concentrated solution of the Chinese medicine compound, add 4 times the amount of purified water, heat in a 60°C water bath, filter the precipitate with absorbent cotton while it is still hot, concentrate under reduced pressure, and then add borneol to obtain a concentrated Chinese medicine solution with a concentration of 1g / ml for use.

[0089] 2) Preparation of hydrogel skeleton: quantitatively weigh the gel skeleton of the hydrogel matrix, dissolve it in water, and make a hydrogel skeleton. Taking the combination of hyaluronic acid and water-soluble chitosan as a hydrogel skeleton as an example, weigh hyaluronic acid and chitosan according to the set mass ratio, add them to distilled water respectively, and make hyaluronic acid solution and chitosan solution; mix them evenly according to the set volume ratio: concentrated Chinese medicine solution: hydrogel skeleton = 5-10:1, and obtain a hydrogel skeleton for standby use. In order to form a three-dimensional network space structure suitable for drug loading, the stirring speed of the hyaluronic acid solution and the chitosan solution after mixing is preferably 200-300rpm.

[0090] 3) Drug loading: Add the concentrated Chinese medicine solution prepared in step 1) to the hydrogel skeleton prepared in step 2) while hot, and stir at the same speed of 200-300 rpm to disperse the drug in the gaps of the hydrogel skeleton to form a hydrogel drug loading system.

[0091] 4) Oil-in-oil encapsulation: Cool the hydrogel drug-carrying system to 35-45°C, add glycerol to form an oil film on the gaps of the hydrogel skeleton, encapsulate the concentrated Chinese medicine solution in the gaps of the hydrogel skeleton, and then cool to room temperature to obtain a Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery. In order to uniformly coat the gaps of the hydrogel skeleton with glycerol without breaking it and not affecting the gel skeleton system, the stirring speed of the oil-in-oil encapsulation in the preparation method described in this embodiment is preferably set to 50-150 rpm.

[0092] In addition, this embodiment also provides an application of the aforementioned traditional Chinese medicine hydrogel composition in preventing and treating various anorectal surgical wound infections, specifically including preventing the formation of bacterial biofilms on various anorectal surgical wounds and promoting the healing of surgical wounds.

[0093] Example 2

[0094] This embodiment is to prepare a Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery by the method described in Example 1. The Chinese medicine raw materials used in this embodiment are all purchased from the market; the hyaluronic acid used is non-cross-linked sodium hyaluronate (brand, Tianguangyuan Biological, molecular weight 1 million to 1.8 million Da); the water-soluble chitosan used is carboxymethyl chitosan (Sinopharm Group Chemical Reagent Co., Ltd., molecular weight = 150 to 250 kDa, degree of substitution 35 to 45%); glycerol (glycerol, brand: Shanghai Test National Medicine, analytical purity) The specific preparation process is as follows:

[0095] Step 1: Extraction and preparation of concentrated Chinese medicine solution

[0096] Weigh 12g of Coptis chinensis, 12g of Scutellaria baicalensis, 12g of Phellodendron chinense, 12g of Curcuma longa, 9g of Rhubarb, 12g of Forsythia suspensa, 12g of Sophora flavescens, 18g of Angelica sinensis, 36g of Rehmannia glutinosa, 12g of Portulaca oleracea, 9g of Lithospermum officinale, and 2g of Borneol. Keep Borneol aside for later use. Mix the remaining 11 herbs, wash with water until the water is clear, add twice the amount of water and soak for 30 minutes; start decocting:

[0097] First decoction, add 5 times the amount of water, simmer for 60 minutes, filter the original liquid, and set aside the filtrate;

[0098] Continue to decoct, add 4 times the amount of water, simmer for 45 minutes, filter the original solution, and set aside the filtrate;

[0099] Decoction again, add 3 times the amount of water, simmer for 30 minutes, filter the original liquid, and set aside the filtrate;

[0100] The three decoction filtrates were combined and concentrated at a constant temperature of 60°C to prepare a concentrated Chinese medicine stock solution with a concentration of 1 g / ml;

[0101] Then, ethanol is added until the ethanol content reaches 70%, the mixture is allowed to stand for 24 hours, filtered, and the filtrate is subjected to de-alcoholization by vacuum distillation at a constant temperature of 60°C to obtain a Chinese medicine compound alcohol precipitation concentrate;

[0102] Finally, take the alcohol-precipitated concentrated solution of the Chinese medicine compound, add 4 times the amount of purified water, heat it in a 60°C water bath, filter the precipitate with absorbent cotton while it is still hot, concentrate it under reduced pressure, and then add borneol to obtain a concentrated Chinese medicine solution with a concentration of 1 g / ml for use.

[0103] Step 2: Preparation of hydrogel skeleton

[0104] While preparing the concentrated Chinese medicine solution, weigh 30 g of non-cross-linked sodium hyaluronate and 40 g of carboxymethyl chitosan, add them into 1000 mL of distilled water respectively, heat to 60° C. to fully dissolve the drugs, and obtain 30 mg / mL of sodium hyaluronate solution and 40 mg / mL of chitosan solution; then slowly add the chitosan solution to the sodium hyaluronate solution, control the addition to be completed within 10 min, and stir at 200 rpm while adding to obtain a hydrogel skeleton for later use.

[0105] Step 3: Drug loading

[0106] The extracted concentrated Chinese medicine solution was added to the hydrogel skeleton solution while hot (60°C), with the volume ratio of concentrated Chinese medicine solution to hydrogel skeleton being 10:1. Stirring was continued at 200 rpm for 15 min to fully disperse the concentrated Chinese medicine solution in the hydrogel skeleton to form a drug-carrying system.

[0107] Step 4: Oil-packaging

[0108] The temperature of the drug-carrying system solution was lowered to 40°C, glycerol was added in an amount of 9% of the total mass of the hydrogel matrix, and the stirring speed was reduced to 80 rpm. The mixture was stirred for 20 minutes and then allowed to stand and cool to room temperature to obtain a traditional Chinese medicine hydrogel composition (product 1) for preventing and treating postoperative wound infection of anorectal surgery. The microstructure of the composition is as follows: Figure 1 shown.

[0109] Example 3

[0110] In this embodiment, the hydrogel is prepared using the traditional Chinese medicine compound prescription, which is the classic prescription of traditional Chinese medicine surgery in "Yi Zong Jin Jian". The classic prescription: 9g of Coptis chinensis, 15g of Angelica sinensis, 9g of Phellodendron chinense, 30g of Rehmannia glutinosa, 9g of Curcuma longa, 360g of Sesame Oil, and 120g of Yellow Wax.

[0111] The preparation method of the hydrogel is different from Example 2 in that the preparation method of the concentrated Chinese medicine stock solution is different from Example 2, and the remaining steps and the drugs such as hyaluronic acid, water-soluble chitosan and glycerol used are consistent with Example 2. The preparation method of the concentrated Chinese medicine solution is as follows:

[0112] Since 360g of sesame oil and 120g of yellow wax are the bases for preparing the ointment, these two ingredients are discarded in this embodiment. Weigh 9g of Coptis chinensis, 15g of Angelica sinensis, 9g of Phellodendron chinense, 30g of Radix Rehmanniae, and 9g of Curcuma longa, mix and wash with water until clear water is available, add 2 times the amount of water and soak for 30min, and start decocting:

[0113] First decoction, add 5 times the amount of water, simmer for 60 minutes, filter the original liquid, and set aside the filtrate;

[0114] Continue to decoct, add 4 times the amount of water, simmer for 45 minutes, filter the original solution, and set aside the filtrate;

[0115] Decoction again, add 3 times the amount of water, simmer for 30 minutes, filter the original liquid, and set aside the filtrate;

[0116] The three decoction filtrates were combined and concentrated at a constant temperature of 60°C to prepare a concentrated Chinese medicine stock solution with a concentration of 1 g / ml;

[0117] Then, ethanol is added until the ethanol content reaches 70%, the mixture is allowed to stand for 24 hours, filtered, and the filtrate is subjected to de-alcoholization by vacuum distillation at a constant temperature of 60°C to obtain a Chinese medicine compound alcohol precipitation concentrate;

[0118] Finally, take the ethanol precipitation and concentration solution of the traditional Chinese medicine compound, add 4 times the amount of purified water, heat it in a water bath at 60°C, filter the precipitate while it is hot with absorbent cotton, concentrate it under reduced pressure, and then add borneol to obtain a concentrated traditional Chinese medicine solution with a concentration of 1 g / ml.

[0119] Then add the concentrated traditional Chinese medicine solution into the water-in-oil encapsulation of the hydrogel skeleton to obtain a hydrogel (Product 2), and its drug loading and water-in-oil encapsulation steps are the same as those in Example 2.

[0120] Example 4

[0121] In this example, the antibacterial properties of the traditional Chinese medicine hydrogel composition (Product 1) prepared in Example 2 were investigated, and at the same time, the classical formula hydrogel (Product 2) prepared in Example 3 and the classical formula ointment were used as comparisons. The preparation method of the classical formula ointment is (preparing Coptis chinensis ointment by the "frying until withered" method in "Golden Mirror of Medicine"): According to the classical formula ratio: 9 g of Coptis chinensis, 15 g of Angelica sinensis, 9 g of Phellodendron amurense, 30 g of Rehmannia glutinosa, 9 g of Curcuma longa, weigh the Chinese herbal medicine pieces, directly put the medicine pieces into 5 times the amount of sesame oil, fry at 200°C for 4 h, remove the residue, add 1 time the amount of yellow wax, mix well, cool, solidify, and collect the ointment to obtain the classical formula ointment (Product 3).

[0122] The investigation method is as follows: Use the K-B method to determine the antibacterial effects of each product against Escherichia coli and Staphylococcus aureus.

[0123] In a biosafety cabinet, for the prepared standard suspensions of Escherichia coli and Staphylococcus aureus with a turbidity of 0.5 McFarland, use a sterile cotton swab to evenly smear and rotate the petri dish by 60° on the M-H agar plate, repeat the streaking three times in total, and finally smear the bacteria on the edge of the agar as well. Place the prepared drug sensitivity test paper (soak sterile circular filter paper with a diameter of 1 cm in the classical formula ointment, the classical formula temperature-sensitive hydrogel, and the traditional Chinese medicine temperature-sensitive hydrogel composition of the present invention in a 4°C refrigerator overnight to fully infiltrate the drug), and place it flat on the agar plate medium. After placing the drug sensitivity test paper with a diameter of 6 mm, place the plate face up in a constant temperature incubator at 35°C for 24 hours. After 24 hours, the experimental results can be observed, as shown in Table 1 and Figures 2 to 7 as shown.

[0124] Table 1. The diameters of the antibacterial zones of each product (x±s, mm)

[0125]

[0126] From Table 1 and Figures 2 to 7The results show that compared with the classic ointment of product 3, the Chinese medicine hydrogel composition of the present invention (product 1) and the classic hydrogel (product 2) have better antibacterial effects on Escherichia coli and Staphylococcus aureus, and the antibacterial effect of the Chinese medicine hydrogel composition of the present invention (product 1) is better than that of the classic hydrogel (product 2). This shows that the Chinese medicine compound of the Chinese medicine hydrogel composition of the present invention is better than the classic ointment, and the hydrogel dosage form is better than the ointment dosage form.

[0127] Example 5

[0128] This example is to investigate the preventive and therapeutic effect of the traditional Chinese medicine hydrogel composition prepared in Example 2 on inhibiting the formation of bacterial biofilm on contaminated wounds on the backs of mice and promoting wound healing.

[0129] In this embodiment, the test samples include:

[0130] Sample 1: The traditional Chinese medicine hydrogel composition prepared in Example 2 (Product 1).

[0131] Sample 2: The concentrated Chinese medicine solution with a concentration of 1 g / ml prepared in Example 2 was cooled to room temperature.

[0132] Sample 3: The hydrogel skeleton prepared in Example 2 was not subjected to the drug loading step, but was subjected to oil-in-package encapsulation. The encapsulation operation was the same as that in Example 2, and the sample was cooled to room temperature.

[0133] Sample 4: hydrogel prepared in Example 3 (product 2).

[0134] Sample 5: Ointment prepared according to the classic formula prepared in Example 4 (Product 3).

[0135] The inspection process is as follows:

[0136] 1) Modeling: A rat back contaminated wound model was used. Thirty healthy rats were selected for experimental study. The skin was prepared and a circular wound with a diameter of about 2.0 cm was cut with a wound making device deep into the muscular layer. The thickness of the muscular layer wound was about 0.3 cm. After hemostasis, 0.5 ml of Staphylococcus aureus (ATCC6583 10 6 The wound was soaked in Vaseline gauze, dressings and tape for 1 hour, and adaptive feeding was given after surgery. The covering was removed after 48 hours. The wound was found to have purulent secretions and a foul odor. The formation of bacterial biofilm on the wound was observed on days 3, 5 and 7. The model was successful if the characteristic structure of bacterial biofilm was detected.

[0137] 2) Grouping: The rats with successful modeling were divided into 5 groups.

[0138] Group 1: hydrogel treatment group of the present invention; treatment method: the traditional Chinese medicine hydrogel composition (product 1) prepared in Example 2 was applied to the wound surface, covered and fixed with sterile gauze, once a day until the end of the in vivo experiment;

[0139] Group 2: concentrated Chinese medicine liquid treatment group; treatment method: the concentrated Chinese medicine liquid with a concentration of 1 g / ml prepared in Example 2 was applied to the wound surface, and then covered and fixed with sterile gauze, once a day until the end of the in vivo experiment;

[0140] Group 3: hydrogel skeleton treatment group; treatment method: the hydrogel skeleton prepared in Example 2 was applied to the wound surface, and then covered and fixed with sterile gauze, once a day until the end of the in vivo experiment;

[0141] Group 4: Classic hydrogel treatment group; treatment method: The hydrogel prepared in Example 3 (Product 2) was applied to the wound surface and covered and fixed with a dressing once a day until the end of the in vivo experiment;

[0142] Group 5: Classic ointment treatment group; Treatment method: Apply the ointment (product 3) prepared by the classic formula prepared in Example 4 to the wound surface, cover and fix with dressing, once a day, until the end of the in vivo experiment

[0143] 3) Sampling: All experimental specimens were collected under sterile conditions. After 14 days of treatment, the rats were killed by overdose of anesthesia.

[0144] The inspection indicators are as follows:

[0145] (1) Determination of wound healing rate:

[0146] The wound healing was observed on the 3rd, 7th and 14th days after treatment. Image J software was used to measure and compare the changes in wound area before and after treatment in each group. The wound healing on the 7th and 14th days after treatment was analyzed, and the wound healing rate was calculated.

[0147] Wound healing rate (%) = (original wound area - unhealed wound area) / original wound area × 100%'

[0148] The results are shown in Table 2 and Figure 8 Show.

[0149] Table 2. Comparison of wound healing rates in each group of rat animal model (%)

[0150]

[0151] From Table 2 and Figure 8It can be seen from the results that the wound healing rates of the Chinese medicine hydrogel composition (product 1) and the classic prescription hydrogel (product 2) of the present invention are better than those of the classic prescription ointment of product 3, and the healing rate of the Chinese medicine hydrogel composition (product 1) of the present invention is better than that of the classic prescription hydrogel (product 2), indicating that the Chinese medicine compound of the Chinese medicine hydrogel composition of the present invention is better than the classic prescription, and the hydrogel dosage form is better than the ointment dosage form; in addition, the wound healing rates of the Chinese medicine preparation concentrate and the hydrogel skeleton of the present invention are both lower than that of the Chinese medicine hydrogel composition (product 1), indicating that the combination of the Chinese medicine preparation concentrate and the hydrogel skeleton enhances the effect of promoting wound healing.

[0152] (2) Bacterial biofilm observation:

[0153] Qualitative identification: The infected wound tissues of rats were clamped on the 3rd and 7th days after surgery, and the biofilm growth was observed under a scanning electron microscope and statistically compared. The columnar or mushroom-shaped typical structures observed under a scanning electron microscope indicated the formation of bacterial biofilm. Fig. 9 and Fig.10 shown.

[0154] The biofilm growth was graded as follows: Grade I: free-floating planktonic cells were visible, and cells adhered to the biofilm; Grade II: microcolonies and cell clusters were formed; Grade III: microcolonies were interconnected through extracellular matrix fibers, forming microcolonies (towers) with a spider web appearance; Grade IV: towers with underground channels and amorphous extracellular material were formed, in a honeycomb pattern. The biofilm growth was graded and assigned scores of 1, 2, 3, and 4, respectively. The statistical results are shown in Table 3.

[0155] Table 3. Comparison of biofilm growth in each group of rat animal model M (P25, P75)

[0156]

[0157] As can be seen from the results in Table 3, compared with the classic ointment of product 3, the Chinese medicine hydrogel composition of the present invention (product 1) and the classic hydrogel (product 2) have better inhibitory effects on bacterial biofilms, and the inhibitory effect of the Chinese medicine hydrogel composition of the present invention (product 1) is better than that of the classic hydrogel (product 2). It shows that the Chinese medicine compound of the Chinese medicine hydrogel composition of the present invention is better than the classic prescription, and the hydrogel dosage form is better than the ointment dosage form. In addition, the antibacterial effects of the Chinese medicine preparation concentrate and the hydrogel skeleton of the present invention are not as good as those of the Chinese medicine hydrogel composition (product 1), which shows that the combination of the Chinese medicine preparation concentrate and the hydrogel skeleton improves its antibacterial effect and can effectively prevent the formation of bacterial biofilms.

[0158] (3) Pathological observation of granulation tissue on wound surface:

[0159] On the 7th and 14th days after surgery, the newly formed granulation tissue from the edge of the wound to the center of the wound was collected, with a size of about 0.5cm*0.5cm. After successful collection, it was immediately placed in a 4% paraformaldehyde solution for fixation for 24 hours, routinely dehydrated and transparent, and then embedded in paraffin. 4μm continuous sections were made for pathological observation, and the growth of capillaries and fibroblasts in the granulation tissue of the wound in each group of the rat animal model was compared. Fig.11 As shown in the figure, it can be seen that the Chinese medicine hydrogel composition of the present invention has the best effect of inhibiting inflammatory response and promoting wound healing compared with concentrated Chinese medicine liquid, hydrogel skeleton and classic hydrogel, which proves the advantage of the Chinese medicine hydrogel composition of the present invention in promoting the growth of capillaries and fibroblasts in granulation tissue of wound and promoting wound healing.

[0160] At the same time, granulation tissue near the edge of the wound was obtained, fixed in Carnoy's solution for 45 minutes, embedded in paraffin, sliced, and stained with conventional HE. Observed under a light microscope, such as Figure 12 to Figure 14 As shown. Specifically, the light microscope and MPIAS-400 computer color pathology graphic analysis system were used to statistically analyze the capillaries and fibroblasts of the wound granulation tissue in each group of the rat animal model. The specific operations are as follows: ① General observation; ② Observe 5 fields of view for each specimen, count the number of fibroblasts in the granulation tissue, and calculate the average value (number of fibroblasts / average per field of view); ③ Observe 3 fields of view for each specimen, count the number of new capillaries, and calculate the average value per field of view. The results are shown in Tables 4 and 5.

[0161] Table 4. Comparison of capillaries in wound granulation tissue of each group in rat animal model (x±s)

[0162]

[0163] As can be seen from the results of Table 4, the capillary growth of granulation tissue of the Chinese medicine hydrogel composition (product 1) and the classic prescription hydrogel (product 2) of the present invention is better than that of the classic prescription ointment of product 3, and the capillary growth of granulation tissue of the Chinese medicine hydrogel composition (product 1) of the present invention is better than that of the classic prescription hydrogel (product 2). It shows that the Chinese medicine compound of the Chinese medicine hydrogel composition of the present invention is better than the classic prescription, and the hydrogel dosage form is better than the ointment dosage form. In addition, the capillary growth of granulation tissue of the Chinese medicine preparation concentrate and the hydrogel skeleton of the present invention is not as good as that of the Chinese medicine hydrogel composition (product 1), indicating that the combination of the Chinese medicine preparation concentrate and the hydrogel skeleton enhances its ability to promote the growth of granulation tissue capillaries.

[0164] In addition, the results of light microscopy observation Figure 12 to Figure 14 It also shows the superior therapeutic effect of the Chinese medicine hydrogel of the present invention, wherein Fig.12 For wounds treated with classic ointments, wound infection, tissue necrosis, and tissue structure destruction; Fig.13The wound surface treated with the classic hydrogel was infected and infiltrated with a large number of inflammatory cells; Fig.14 In the wound surface treated with the hydrogel of the present invention, the infiltration of inflammatory cells on the wound surface is reduced, and the capillaries of the granulation tissue grow well.

[0165] Table 5. Comparison of fibroblasts in wound granulation tissue of each group in rat animal model (x±s)

[0166]

[0167] As can be seen from the results of Table 5, the growth of granulation tissue fibroblasts of the Chinese medicine hydrogel composition (product 1) and the classic prescription hydrogel (product 2) of the present invention is better than that of the classic prescription ointment of product 3, and the growth of granulation tissue fibroblasts of the Chinese medicine hydrogel composition (product 1) of the present invention is better than that of the classic prescription hydrogel (product 2). It shows that the Chinese medicine compound of the Chinese medicine hydrogel composition of the present invention is better than the classic prescription, and the hydrogel dosage form is better than the ointment dosage form. In addition, the growth of granulation tissue fibroblasts of the Chinese medicine preparation concentrate and the hydrogel skeleton of the present invention are not as good as that of the Chinese medicine hydrogel composition (product 1), indicating that the combination of the Chinese medicine preparation concentrate and the hydrogel skeleton enhances its ability to promote the growth of granulation tissue fibroblasts.

[0168] from Figure 12 to Figure 14 (The three pictures are pathological sections of granulation tissue on the wound surface 7 days after surgery) It can also be seen that the wound surface treated with the classic ointment is infiltrated by inflammatory cells and a large amount of tissue necrosis ( Fig.12 ); the wound surface treated with the classic hydrogel was also infected, with necrotic tissue and bacterial colonization ( Fig.13 ); while the granulation tissue of the wound surface treated with the hydrogel of the present invention grew well ( Fig.14 ), which further shows that the Chinese medicine hydrogel composition (product 1) of the present invention can inhibit bacterial infection of wound surface, prevent bacteria from forming biofilm on wound surface, and promote the growth of granulation tissue and capillaries on wound surface, thus facilitating wound healing.

[0169] Example 6

[0170] This example is to investigate the influence of the selection and dosage of the gel skeleton of the traditional Chinese medicine hydrogel composition of the present invention on the molding properties, mechanical stability, and drug effect of the composition. The details are as follows:

[0171] This example uses the traditional Chinese medicine hydrogel composition (product 1) prepared in Example 2 as the basis for investigation. The gel compositions involved in the investigation are different from product 1 except for the material selection and dosage of the gel skeleton and the preparation method of the hydrogel skeleton. The remaining components, dosages and preparation processes are consistent with those in Example 2.

[0172] The material selection and dosage of the gel skeleton in each traditional Chinese medicine hydrogel composition used for investigation are shown in Table 6.

[0173] Table 6. Materials of gel skeleton in each traditional Chinese medicine hydrogel composition (g)

[0174]

[0175] Wherein, the hydrogel skeleton of product 4 and product 5 is respectively non-crosslinked sodium hyaluronate and carboxymethyl chitosan dissolved in 1000mL distilled water, heated to 60 ° C, the drug is fully dissolved, and a gel skeleton solution of 70mg / mL is obtained, and then the drug is loaded. The preparation method of the remaining products is consistent with Example 2, only carboxymethyl chitosan is replaced with corresponding other materials. At the same time, this embodiment also prepares a Chinese medicine compound hydrogel (product 12) as a comparison according to Example 1 disclosed in Chinese patent document CN110624054B.

[0176] In this embodiment, the molding performance and mechanical stability of the product composition are evaluated by the shaping ability and the shaping time of the prepared traditional Chinese medicine hydrogel composition, and the drug effect of the product composition is evaluated by the observation results of the bacterial biofilm on the wound surface of rats. Among them, the process of investigating the drug effect of the product composition is consistent with that of Example 5, and the shaping ability and the shaping time experiment of the product composition are as follows:

[0177] Each Chinese medicine hydrogel composition was filled into a mold, molded into a column with a diameter of 1 cm and a height of 2 cm, and placed in an environment of 36°C to observe whether each Chinese medicine hydrogel composition can be molded and the maintenance time of each medicine column. The maintenance time refers to the time to completely spread and dry at 36°C. The results of the investigation are shown in Table 7.

[0178] Table 7. Forming effect and bacterial biofilm inhibition effect of each Chinese medicine hydrogel composition

[0179]

[0180] As can be seen from the results in Table 7, each product can be successfully molded into a drug column, but the shaping time is different. As for the natural polymer material pointed out by the present invention, the non-cross-linked sodium hyaluronate and carboxymethyl chitosan combination is used as the skeleton material, and the product shaping time is the longest, and the effect of inhibiting the growth of wound biofilm is the best. Although the product 12 prepared according to the patent document CN110624054B can also be well shaped and has a better shaping ability, its effect on inhibiting the growth of wound biofilm is relatively poor, which is not as good as any traditional Chinese medicine hydrogel composition product of the present invention, which further illustrates the superior performance of the traditional Chinese medicine hydrogel composition of the present invention.

[0181] Example 7

[0182] This example is to investigate the effect of the amount of glycerol used as the encapsulating agent of the traditional Chinese medicine hydrogel composition of the present invention on the stability of the composition and the drug effect. The details are as follows:

[0183] This example also uses the Chinese medicine hydrogel composition (product 1) prepared in Example 2 as the basis for investigation. The gel compositions involved in the investigation are different from product 1 except for the amount of glycerol used. The remaining components, amounts and preparation processes are consistent with Example 2. The amount of glycerol used in each Chinese medicine hydrogel composition used for investigation is shown in Table 8.

[0184] Table 8. Glycerol dosage in each Chinese medicine hydrogel composition (%)

[0185] Glycerol dosage Product 13 Products 14 Product 15 Product 1 Products 16 Product 17 Percentage of total mass of hydrogel matrix (%) 0 7 8 9 10 11

[0186] Among them, product 13 does not use glycerol, that is, there is no oil-packaging process, and the drug can be directly cooled to room temperature after loading.

[0187] In this example, the stability of the prepared traditional Chinese medicine hydrogel composition is evaluated by the water loss rate of the composition, and the drug effect of the composition is evaluated by the observation results of bacterial biofilm on the wound surface of rats. Similarly, the bacterial biofilm observation experiment process is consistent with Example 5. The water loss experiment of the composition is as follows:

[0188] Each Chinese medicine hydrogel composition was filled into a mold, molded into a short column with a diameter of 3 cm and a height of 2 cm, placed on a multilayer filter paper, and allowed to stand at 36°C for 5 minutes. Each drug column was weighed before and after standing (excluding the filter paper), and the water loss rate was calculated. A water loss rate of less than 50% was considered acceptable.

[0189] Water loss rate (%) = (weight before water loss - weight after water loss) / weight before water loss × 100%;

[0190] The investigation results are shown in Table 9.

[0191] Table 9. Water loss rate and bacterial biofilm inhibition effect of each Chinese medicine hydrogel composition

[0192]

[0193] It can be seen from the results in Table 7 that the water loss rate of each Chinese medicine hydrogel composition first decreases and then increases with the increase of glycerol dosage. When the glycerol dosage is 9% of the total mass of the hydrogel matrix, the water loss rate of the composition is the lowest; when the glycerol dosage is 8-10% of the total mass of the hydrogel matrix, the water loss rate is less than 50%, which is a qualified product; when the glycerol dosage is less than 8% of the total mass of the hydrogel matrix and greater than 10% of the total mass of the hydrogel matrix, the water loss rate of the composition is greater than 50%. This is because when the glycerol dosage is too small, it cannot form a good blocking effect on the Chinese medicine liquid in the gel skeleton, resulting in the loss of the medicine liquid and water, and when the glycerol dosage is too large, the shape-deformation ability of the composition will deteriorate, resulting in the collapse of the medicine column, and then causing the loss of water and medicine liquid.

[0194] In addition, from the perspective of the inhibition of wound biofilm growth by each hydrogel composition, the results are also relatively related to its water loss rate. If the amount of glycerol is too little, the gel skeleton cannot wrap the traditional Chinese medicine liquid well, resulting in unsatisfactory treatment and antibacterial effects; while excessive amount of glycerol may lead to reduced stability of the hydrogel, resulting in the destruction of the three-dimensional network structure of the hydrogel during the administration process, resulting in sudden release of drugs, resulting in unsatisfactory treatment and antibacterial effects; that is, excessive or insufficient amount of glycerol will lead to rapid release of drugs, and the expected sustained-release effect cannot be achieved, which is not conducive to the treatment of anorectal surgical wounds that require long-term and stable release of drugs.

[0195] Example 8

[0196] This example verifies the clinical effect of the Chinese medicine hydrogel composition for preventing and treating wound infection after anorectal surgery of the present invention. The products used in this example are the Chinese medicine hydrogel composition (product 1) prepared in Example 2 and the classic prescription ointment prepared in Example 4 as comparison.

[0197] The verification process is as follows:

[0198] The cases were from patients with open drainage after anal fistula surgery in the Anorectal Department of Zhenjiang Traditional Chinese Medicine Hospital from January 2022 to December 2023. The clinical trial of this example passed the ethics review of the ethics committee and obtained informed consent from the patients.

[0199] Patients after anal fistula surgery were included and randomly divided into a treatment group (treated with the Chinese medicine hydrogel composition of the present invention) and a control group (treated with a classic prescription oil ointment), 7 days as a course of treatment, continuous treatment, observation, until healing, and follow-up for 6 months. In this embodiment, wound healing speed, secretions, granulation tissue growth, pain index, etc. are used as efficacy observation indicators to evaluate the clinical efficacy of Chinese medicine compound hydrogel, and statistically analyze the differences between Chinese medicine compound hydrogel and traditional therapy in wound healing state, postoperative follow-up recurrence rate, etc. Among them, the observation method of granulation tissue growth is the same as that of Example 5. Clinical anorectal postoperative infection wounds are mostly treated by surgical debridement, so postoperative wound material collection does not constitute a hazard to healing, and the wound granulation tissue near the incision edge can be taken for investigation; the wound healing speed is compared with the postoperative wound healing time.

[0200] The results of the investigation showed that the wounds of the patients in the Chinese medicine hydrogel composition group of the present invention were completely epithelialized, and no poor healing to form chronic ulcer sinus tracts was observed. No recurrence was observed during the follow-up for 6 months. However, in the control group, 5 patients still failed to completely epithelialize their wounds after continuous dressing changes for more than 2 months in the outpatient clinic, and were clinically judged to have formed chronic ulcer sinus tracts (poor healing rate 10%). Fig.15 As shown. Patients with complete epithelialization of the wound were followed up for 6 months, and 3 cases recurred (recurrence rate 6.7%). Patients with poor healing and recurrence underwent reoperation after communication, and recovered after the treatment group regimen. Statistical results showed that the postoperative wound healing time in the treatment group was 27-36 days, with an average of (28.31±2.54) days, and that in the control group was 31-43 days, (31.52±3.35) days. The treatment group was significantly shorter than the control group, and the difference was statistically significant (P<0.05). The granulation tissue growth state, cure rate, and effective rate of the treatment group were better than those of the control group, and the difference was statistically significant (P<0.05). The results are shown in Table 10.

[0201] Table 10. Comparison of granulation tissue growth scores between the two groups of patients (x±s)

[0202]

[0203] Note: Treatment group vs control group: P>0.05 on the second day after surgery, ※P<0.05 on the second and fifteenth days after surgery.

[0204] It can be seen from the results in Table 10 that the growth of granulation tissue capillaries in the treatment group using the traditional Chinese medicine hydrogel composition of the present invention (Product 1) is better than that in the control group using the classic prescription ointment (Product 3), which proves that the traditional Chinese medicine hydrogel composition of the present invention can indeed promote the growth ability of granulation tissue on the wound surface of patients.

[0205] Granulation tissues were taken from the wounds near the 7th and 14th day margins of the two groups of patients for examination. Fig.16 and Fig.17 shown. Fig.16 This is a bacterial smear of the wound surface of a patient after anorectal surgery. The upper picture is the control group: Staphylococcus and Streptococcus can be seen growing in clusters in the gaps between tissue fragments on the wound surface, which is a characteristic of the growth and formation process of the composite bacterial biofilm. The lower picture is the treatment group: no obvious bacterial growth or aggregation was observed after treatment with the TCM compound hydrogel. Fig.16 The left picture shows the pathological sections of the wound after anorectal surgery. The left picture shows the control group: the pathological sections of the wound after anorectal surgery show a large number of inflammatory cells infiltration, sparse fibroblasts, and poor capillary growth. The right picture shows the treatment group: after the intervention treatment of the Chinese medicine hydrogel composition, the infiltration of inflammatory cells decreased, and the growth of fibroblasts and capillaries improved.

[0206] The treatment effect of the patients was evaluated with the following criteria: cured: the wound surface was completely epithelialized, no ulceration occurred after 1 week of observation, and the symptom score was reduced by >90% compared with that before treatment; markedly effective: the wound surface was reduced by ≥75%, and the symptom score was reduced by 70%~90%; effective: the wound surface was reduced by ≥25%, and the symptom score was reduced by 30%~70%; ineffective: the wound surface did not change or expanded, and the symptom score was reduced by less than 30%. The results are shown in Table 11.

[0207] Table 11. Comparison of overall efficacy between the two groups of patients (n / %)

[0208]

[0209] It can be seen from Table 11 that among the 30 patients in the treatment group using the Chinese medicine hydrogel composition of the present invention, 26 were cured, no treatment was ineffective, the cure rate was 87%, and the effective rate was 100%; while among the 30 patients in the control group, 20 were cured, 5 were ineffective, the cure rate was 62%, and the effective rate was 82.8%; in comparison, the total effective rate of the treatment effect of the Chinese medicine hydrogel composition of the present invention was increased by nearly 17.2%, and the cure rate was increased by 25%, with significant effects.

[0210] Therefore, in general, the present invention takes the classic paste and powder of traditional Chinese medicine as the basic formula, combines clinical experience, and performs modification and optimization to form a Chinese medicine compound, adopts natural hydrogel polymer material as the skeleton to prepare a temperature-sensitive in situ hydrogel, and uses glycerol as the encapsulating agent to encapsulate the concentrated liquid of the drug compound therein to form a stable drug delivery system; thereby realizing the combination of Chinese medicine preparations and hydrogels, effectively solving the shortcomings of traditional pastes and powders such as oil pollution, poor formability, and inconvenience in use, as well as the problems of easy contamination, bacterial colonization and growth, and formation of bacterial biofilms in open drainage incisions after clinical anorectal surgery. Clinical application has confirmed that the Chinese medicine hydrogel composition of the present invention has the function of directly acting on the local lesion, the thermosensitive in situ hydrogel is simple to prepare, easy to use, has good adhesion and tissue compatibility, can prolong the retention time of the drug at the medication site, and improve bioavailability; the effective ingredients of the Chinese medicine compound can effectively prevent the formation of bacterial biofilm on the anorectal wound surface, and the thermosensitive Chinese medicine compound in situ hydrogel can form a moist protective film on the wound surface after anorectal surgery, forming a microenvironment that is conducive to wound healing, and exerting anti-inflammatory, analgesic, detumescent, blood-activating, and myogenic effects, thereby inhibiting infection, relieving swelling and pain, bleeding, exudation and other symptoms, promoting recovery, and effectively alleviating the patient's pain, and has important medical value.

[0211] Finally, it should be noted that: for those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, no matter from which point of view, the embodiments should be regarded as exemplary and non-restrictive. In addition, it should be understood that although this specification is described in accordance with the implementation mode, it does not contain only one technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in the embodiments can also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A Chinese medicine hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery, the composition comprising a Chinese medicine compound and a hydrogel matrix, characterized in that: The Chinese medicine compound is composed of the following 12 herbs composition: Main medicine: Coptis chinensis, Scutellaria baicalensis, Ministerial drugs: Forsythia suspensa, Phellodendron chinense, Rhubarb, Auxiliary drugs: turmeric, angelica, raw earth, lithospermum officinale, sophora flavescens, purslane, Adjuvant: borneol; The hydrogel matrix includes a gel skeleton and an encapsulating agent; The gel skeleton is a natural hydrogel polymer material; The encapsulating agent is glycerol, and its usage is 8-10% of the total mass of the hydrogel matrix.

2. The Chinese medicine hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery according to claim 1, characterized in that: The 12 herbs in the Chinese herbal compound are as follows by weight: 12-36 parts of Coptis chinensis, 12-36 parts of Scutellaria baicalensis, 12-36 parts of Phellodendron chinense, 12-36 parts of Curcuma longa, 9-27 parts of Rhubarb, 12-36 parts of Forsythia suspensa, 12-36 parts of Sophora flavescens, 18-54 parts of Angelica sinensis, 36-108 parts of Rehmannia glutinosa, 12-36 parts of Portulaca oleracea, 9-27 parts of Lithospermum officinale, and 2-6 parts of Borneol.

3. The Chinese medicine hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery according to claim 1, characterized in that: The hydrogel matrix gel skeleton is any one or a combination of hyaluronic acid, alginate, water-soluble chitosan, cellulose, gelatin, agarose, silk protein, and collagen.

4. The Chinese medicinal hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery according to claim 3, characterized in that: The gel skeleton of the hydrogel matrix is ​​a combination of hyaluronic acid and water-soluble chitosan, and the mass ratio of the two is 2-4:3-5.

5. The Chinese medicinal hydrogel composition for preventing and treating post-operative wound infection of anorectal surgery according to claim 4, characterized in that: The hyaluronic acid is non-cross-linked sodium hyaluronate, and its molecular weight is 1 to 1.8 million Da; The water-soluble chitosan is carboxymethyl chitosan, the molecular weight of which is 150-250 kDa, and the degree of carboxymethyl substitution is 35-45%.

6. A method for preparing the Chinese medicine hydrogel composition for preventing and treating post-anorectal surgery wound infection according to any one of claims 1 to 5, characterized in that: The steps include: 1) Extraction and preparation of concentrated Chinese medicine solution: quantitatively weigh the raw materials of the Chinese medicine compound, except for borneol, wash the other raw materials with water, decoct and concentrate, and finally add borneol to prepare concentrated Chinese medicine solution; 2) Preparation of hydrogel skeleton: quantitatively weigh the gel skeleton of the hydrogel matrix, dissolve it in an appropriate amount of water, and prepare the hydrogel skeleton; 3) Drug loading: adding the concentrated Chinese medicine solution prepared in step 1) to the hydrogel skeleton prepared in step 2) while hot, stirring, so that the concentrated Chinese medicine solution is dispersed in the gaps of the hydrogel skeleton to form a hydrogel drug loading system; 4) Oil-encapsulation: Add glycerol and stir at an appropriate speed to form an oil film on the hydrogel skeleton gap, encapsulate the concentrated Chinese medicine liquid in the hydrogel skeleton gap, form a stable temperature-sensitive in situ hydrogel drug delivery system, and then cool to room temperature to obtain a Chinese medicine hydrogel composition for preventing and treating postoperative wound infection of anorectal surgery.

7. The method for preparing the Chinese medicine hydrogel composition for preventing and treating post-anorectal surgery wound infection according to claim 6, characterized in that: In step 1), the specific process of extracting and preparing concentrated Chinese medicine solution is as follows: Weigh the raw materials of the Chinese medicine compound quantitatively, except for borneol, wash the remaining raw materials with water, and soak them for 30 minutes; First decoction, add 5 times the amount of water, simmer for 60 minutes, filter the original liquid, and set aside the filtrate; Continue to decoct, add 4 times the amount of water, simmer for 45 minutes, filter the original solution, and set aside the filtrate; Decoction again, add 3 times the amount of water, simmer for 30 minutes, filter the original liquid, and set aside the filtrate; The three decoction filtrates were combined and concentrated at a constant temperature of 60°C to prepare a concentrated Chinese medicine stock solution with a concentration of 1 g / ml; Then, ethanol is added until the content reaches 70%, and the mixture is allowed to stand for 24 hours, filtered, and the filtrate is subjected to de-alcoholization by vacuum distillation at a constant temperature of 60°C to obtain a Chinese medicine compound alcohol precipitation concentrate; Take the alcohol-precipitated concentrated solution of the Chinese medicine compound, add 4 times the amount of purified water, heat in a 60°C water bath, filter the precipitate with absorbent cotton while it is still hot, concentrate under reduced pressure, and add borneol to obtain a concentrated Chinese medicine solution with a concentration of 1 g / ml.

8. The method for preparing the Chinese medicine hydrogel composition for preventing and treating post-anorectal surgery wound infection according to claim 6, characterized in that: In step 2), the specific process of preparing the hydrogel skeleton is as follows: Weigh non-cross-linked sodium hyaluronate and carboxymethyl chitosan according to the mass ratio, add them into distilled water, and prepare 30 mg / mL sodium hyaluronate solution and 40 mg / mL carboxymethyl chitosan solution at 60°C; The carboxymethyl chitosan solution was slowly added to the sodium hyaluronate solution at a volume ratio of 1:1, and the two were stirred at a speed of 200 to 300 rpm to fully mix them to obtain a hydrogel skeleton.

9. The method for preparing the Chinese medicine hydrogel composition for preventing and treating post-anorectal surgery wound infection according to claim 6, characterized in that: In step 3), the drug loading, the volume ratio of the concentrated Chinese medicine solution to the hydrogel skeleton is 5 to 10:1; The temperature of the concentrated Chinese medicine solution is 60°C, and the stirring speed after adding the hydrogel skeleton is 200-300 rpm; In step 4), the oil-in-oil encapsulation is to cool the hydrogel drug-carrying system to 35-40° C., add glycerol, and control the stirring speed of the encapsulation to 50-150 rpm.

10. An application of the traditional Chinese medicine hydrogel composition according to any one of claims 1 to 5, characterized in that: The invention is used in the preparation of drugs for preventing and treating various anorectal surgical wound infections, including the preparation of drugs for preventing the formation of bacterial biofilms on various anorectal surgical wounds and promoting the healing of surgical wounds.

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