CN113616849B - Liquid dressing for external wound care and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of medical liquid dressings, and particularly relates to a liquid dressing for external wound care and a preparation method thereof. The liquid dressing comprises raw materials such as moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, alginate, hyaluronic acid and derivatives thereof, a humectant, a film forming agent, a pH regulator, purified water and the like. The liquid dressing disclosed by the invention can quickly form a transparent dressing film which is strong in fitting property with the surface of a wound, good in air permeability, elastic and soft after being sprayed, maintains a wet healing environment, can efficiently kill pathogenic microorganisms, inhibit inflammatory reaction, quickly stop bleeding and relieve pain, can promote wound repair and tissue regeneration, avoids a prominent scar caused by abnormal hyperplasia of wound tissue, and has extremely beneficial effect on wound care.

Description

Liquid dressing for external wound care and preparation method thereof

Technical Field

The invention belongs to the field of medical liquid dressings, and particularly relates to a liquid dressing for external wound care and a preparation method thereof.

Background

The skin is used as an organ with the largest area of a human body, when the skin is contacted with the external environment, the loss of moisture, electrolyte and plasma protein can be effectively prevented, the invasion of bacteria is resisted, the entry of toxicant is prevented, the mechanical damage is resisted, and the injury to the human body caused by ultraviolet irradiation is resisted. In daily life, skin defects inevitably occur due to diseases such as wounds, burns, scalds, and skin ulcers caused by human lesions (diabetic feet, venous ulcers, bedsores, etc.). Various scholars are engaged in research on active treatment methods for promoting wound repair. In the process of wound repair, the dressing is an indispensable cover, and can effectively provide proper temperature and humidity for the wound surface.

The dressing is selected according to the stage of wound healing, and the medical dressing should have a series of special functions, provide a physical barrier for the wound surface, have low adhesiveness, have filling and hemostatic effects, and the like. The medical dressing is used as a wound surface covering material, can replace damaged skin to play a role of temporary barrier in the wound healing process, can avoid or control wound infection, and provides a good healing environment for the wound surface. The traditional dressing is made of natural plant fibers or animal hair substances, such as gauze, cotton pads, wool, various kinds of oil gauze and the like, the dressing is only a temporary covering material, needs to be replaced within a certain time, and is easy to adhere to a wound in a healing process to cause secondary damage. Based on the insufficient performance of the traditional dressing, the ideal medical dressing has the following functions: (1) the wound surface temperature can be kept, and the formation of epithelial tissues is accelerated; (2) can effectively absorb wound tissue exudates; (3) the paint has good permeability and can effectively block bacteria and harmful particles; (4) has good biocompatibility; (5) storage stability and ease of use. The liquid dressing is prepared by mixing medicinal active ingredient with appropriate dispersion phase, and spraying onto the affected part to achieve the effects of promoting wound healing, sterilizing and relieving inflammation. According to a classification, liquid dressings belong to a third class of medical devices. Most of the existing liquid dressings are only used for preventing wound infection, and rarely have the effects of inhibiting bacteria, diminishing inflammation, promoting wound healing, stopping bleeding, relieving pain and the like, so that the liquid dressing product also has a great space for improving the quality.

Disclosure of Invention

The invention aims to solve the technical problem that most of the existing liquid wound dressings are only used for preventing wound infection, and provides a liquid wound spray dressing which has the effects of inhibiting bacteria, diminishing inflammation, promoting wound healing, stopping bleeding, relieving pain and the like and a preparation method thereof.

In order to solve the technical problems, the invention adopts the technical scheme that:

a liquid dressing for external wound care comprises the following raw material components in percentage by weight: 0.5-2.5% of moxifloxacin hydrochloride, 0.2-1% of heptanine, 0.1-0.5% of chlorobutanol, 2-4% of alginate, 1-2% of hyaluronic acid and derivatives thereof, 2-8% of humectant, 10-20% of film forming agent, a proper amount of pH regulator and the balance of purified water.

Preferably, the liquid dressing for external wound care contains the following raw material components in percentage by weight: 1-2% of moxifloxacin hydrochloride, 0.3-0.8% of heptanine, 0.2-0.4% of chlorobutanol, 2.5-3.5% of alginate, 1.2-1.8% of hyaluronic acid and derivatives thereof, 3-6% of humectant, 12-18% of film forming agent, a proper amount of pH regulator and the balance of purified water.

Preferably, the liquid dressing for external wound care contains the following raw material components in percentage by weight: 1.5% of moxifloxacin hydrochloride, 0.5% of heptanine, 0.3% of chlorobutanol, 3% of alginate, 1.5% of hyaluronic acid and derivatives thereof, 5% of humectant, 15% of film forming agent, a proper amount of pH regulator and the balance of purified water.

Preferably, the alginate is selected from sodium alginate, calcium alginate or potassium alginate.

Preferably, the hyaluronic acid and its derivatives are selected from hyaluronic acid, sodium hyaluronate or calcium hyaluronate.

Preferably, the humectant is selected from propylene glycol, glycerol, butylene glycol or polyethylene glycol.

Preferably, the film forming agent is polyvinyl alcohol, polyvinyl butyral or nitrocellulose.

Preferably, the pH adjusting agent is selected from citric acid, triethanolamine or potassium bicarbonate.

Further, the invention also provides a preparation method of the liquid dressing for external wound care, which comprises the following steps:

(1) Weighing the raw material components according to the weight percentage for later use;

(2) Adding a film forming agent into a proper amount of purified water, heating and continuously stirring to fully dissolve the film forming agent to obtain a solution I;

(3) Adding moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, alginate, hyaluronic acid and derivatives thereof and a humectant into the rest purified water, and continuously stirring to fully dissolve the materials to obtain a solution II;

(4) And mixing the solution I and the solution II, adding a pH regulator, regulating the pH to 7.0 +/-0.5, sterilizing and subpackaging to obtain the liquid dressing for nursing the external wound.

Preferably, the heating temperature in the step (2) is 80-90 ℃.

Moxifloxacin hydrochloride is an 8-methoxy fluoroquinolone antibacterial drug with broad spectrum and antibacterial activity. Moxifloxacin hydrochloride showed broad spectrum antibacterial activity in vitro against gram positive bacteria, gram negative bacteria, anaerobic bacteria, acid fast bacteria and atypical microorganisms such as mycoplasma, chlamydia and legionella. The antibacterial mechanism of action is interference with II, IV topoisomerase, which is a key enzyme in controlling DNA topology and in DNA replication, repair and transcription. Moxifloxacin hydrochloride is also effective against beta-lactam and macrolide antibiotic resistant bacteria.

Pseudo-heptanine is a special amino acid, and is a water-soluble non-protein amino acid contained in leguminous and araliaceae plants. The heptanine can obviously shorten the blood coagulation time, the prothrombin time and the thrombin time. The research finds that the hemostatic effect of the heptanine is probably caused by the vasoconstriction of histamine, and the heptanine can achieve the effect of enhancing the hemostasis by comprehensively influencing the blood coagulation system, the platelet aggregation and the fibrinolysis system of rats, namely activating various endogenous coagulation factors, increasing fibers in plasma, promoting the aggregation of a first phase and a second phase of platelets, inhibiting the content of fibrinogen, and preventing fibrinolysis and thrombosis, so that the heptanine still shows good coagulation effect at low dose.

Chlorobutanol was originally used in ophthalmic preparations or formulations for injection administration at a concentration of 0.5% (W/V) as an antibacterial preservative. Chlorobutanol is also used in cosmetics as a preservative, in cellulose ethers and esters as a plasticizer, and in therapy as a mild sedative and local analgesic.

The alginate dressing is a modern functional dressing made of alginate fibers extracted from natural seaweed plants, is soft in texture, is rich in mannuronic acid and calcium ions, and forms gel through complete exchange of calcium ions Ca & lt 2+ & gt and sodium ions Na & lt + & gt after contacting wound exudate, and the surface gel layer plays a role in protecting a wound surface, avoids bacterial invasion, reduces the possibility of wound infection, and creates a microenvironment beneficial to tissue growth for the wound. The release of calcium ion Ca2+ accelerates the blood coagulation process, effectively promotes wound healing, shortens treatment time and reduces patient suffering.

Compared with the prior art, the invention has the beneficial effects that: the liquid dressing disclosed by the invention can quickly form a transparent dressing film which is strong in fitting property with the surface of a wound, good in air permeability, elastic and soft after being sprayed, maintains a wet healing environment, can efficiently kill pathogenic microorganisms, inhibit inflammatory reaction, quickly stop bleeding and relieve pain, can promote wound repair and tissue regeneration, avoids a prominent scar caused by abnormal hyperplasia of wound tissues, and has extremely beneficial effect on wound care. The liquid dressing has excellent performance and good development potential, provides a new reference for selection of clinical wound dressings, and has wide market application prospect.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. The materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.

Experimental Material

Moxifloxacin hydrochloride, purchased from suzhou koyuan pharmaceutical science co;

heptanine, purchased from Doudieti Biotech limited;

chlorobutanol-purchased from yangzhou iridescent biotechnology limited;

alginate-purchased from Qingdao Fucui seaweed Co.

Example 1

A liquid dressing for external wound care comprises the following raw material components in percentage by weight: 1.5% of moxifloxacin hydrochloride, 0.5% of heptanine, 0.3% of chlorobutanol, 3% of sodium alginate, 1.5% of hyaluronic acid, 5% of propylene glycol, 15% of polyvinyl alcohol, a proper amount of pH regulator and the balance of purified water.

The preparation method of the liquid dressing for external wound care comprises the following steps:

(1) Weighing the raw material components according to the weight percentage for later use;

(2) Adding polyvinyl alcohol into a proper amount of purified water, heating to 85 ℃, and continuously stirring to fully dissolve the polyvinyl alcohol to obtain a solution I;

(3) Adding moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, sodium alginate, hyaluronic acid and propylene glycol into the rest purified water, and continuously stirring to fully dissolve the moxifloxacin hydrochloride, the pseudo-ginseng acid, the chlorobutanol, the sodium alginate, the hyaluronic acid and the propylene glycol to obtain a solution II;

(4) And mixing the solution I and the solution II, adding a pH regulator, regulating the pH to 7.0 +/-0.5, sterilizing and subpackaging to obtain the liquid dressing for external wound care.

Example 2

A liquid dressing for external wound care comprises the following raw material components in percentage by weight: 1.0% of moxifloxacin hydrochloride, 0.8% of heptanine, 0.5% of chlorobutanol, 2% of calcium alginate, 2% of sodium hyaluronate, 3% of glycerol, 18% of polyvinyl butyral, a proper amount of pH regulator and the balance of purified water.

The preparation method of the liquid dressing for external wound care comprises the following steps:

(1) Weighing the raw material components according to the weight percentage for later use;

(2) Adding polyvinyl butyral into a proper amount of purified water, heating to 80 ℃, and continuously stirring to fully dissolve the polyvinyl butyral to obtain a solution I;

(3) Adding moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, calcium alginate, sodium hyaluronate and glycerol into the rest purified water, and continuously stirring to fully dissolve the moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, calcium alginate, sodium hyaluronate and glycerol to obtain a solution II;

(4) And mixing the solution I and the solution II, adding a pH regulator, regulating the pH to 7.0 +/-0.5, sterilizing and subpackaging to obtain the liquid dressing for external wound care.

Example 3

A liquid dressing for external wound care comprises the following raw material components in percentage by weight: 2.0% of moxifloxacin hydrochloride, 0.3% of heptanine, 0.1% of chlorobutanol, 4% of potassium alginate, 1% of calcium hyaluronate, 8% of polyethylene glycol, 12% of nitrocellulose, a proper amount of pH regulator and the balance of purified water.

The preparation method of the liquid dressing for external wound care comprises the following steps:

(1) Weighing the raw material components according to the weight percentage for later use;

(2) Adding nitrocellulose into a proper amount of purified water, heating to 90 ℃, and continuously stirring to fully dissolve the nitrocellulose to obtain a solution I;

(3) Adding moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, potassium alginate, calcium hyaluronate and polyethylene glycol into the rest of purified water, and continuously stirring to fully dissolve the moxifloxacin hydrochloride, the pseudo-ginseng acid, the chlorobutanol, the potassium alginate, the calcium hyaluronate and the polyethylene glycol to obtain a solution II;

(4) And mixing the solution I and the solution II, adding a pH regulator, regulating the pH to 7.0 +/-0.5, sterilizing and subpackaging to obtain the liquid dressing for external wound care.

Hemostasis test

According to different dressing types, 30 rats are randomly divided into a blank control group, a fibrin adhesive positive control group and a liquid dressing experimental group, and each group comprises 10 rats. Molding process: injecting 3% pentobarbital sodium solution into abdominal cavity of rat for anesthesia, supinely fixing on operating table, performing operation layer by layer to open abdomen, fully exposing liver left lobe, cutting off part of left lobe liver tissue, further forming liver bleeding wound surface with length of 20mm and depth of 2mm, after free bleeding for about 15s, sucking wound surface blood with sterile gauze, and respectively applying different dressings on the bleeding wound surface. The blank control group used no material, the positive control group used porcine fibrin adhesive, and the experimental group was spray coated with the liquid dressing of example 1. The bleeding time of each rat was recorded, and the amount of blood was calculated by weighing the sterile gauze before and after use. The results of the experiment are shown in table 1.

TABLE 1 hemostasis test

As can be seen from the experimental results in table 1, the average hemostatic time of the liquid dressing group, the positive control group, and the blank control group of the present invention was 35.7s, 41.2s, and 106.3s, respectively, and the average bleeding amount was 0.26g, 0.33g, and 0.75g, respectively. Therefore, compared with a blank control group and a positive control group, the liquid dressing provided by the invention can obviously shorten the bleeding time of the wound surface, reduce the bleeding amount and further play a role in quickly stopping bleeding.

Bacteriostatic test

The MH broth inoculated with Staphylococcus aureus in the constant temperature shaking table was pipetted into 30ul of sterile MH broth by a pipette gun, and shaken uniformly. Selecting a culture dish containing a solid culture medium, dipping a proper amount of nutrient broth by using a sterile cotton swab, and uniformly coating the nutrient broth on the solid culture medium for later use. And taking out the clean dish bottom, clamping 3 pieces of blank filter paper sheets by using tweezers, and sequentially arranging the blank filter paper sheets at the dish bottom. 20ul drops of the liquid dressing of example 1 were applied to one of the filter paper sheets; replacing a clean gun head, and dropwise adding 20ul 75% ethanol solution onto the filter paper sheet to serve as a positive control; the tip was replaced with a clean tip and 20ul of ultrapure water was added dropwise as a negative control. After the scraps of paper dry, press from both sides with tweezers and get the scraps of paper and put into the culture medium and paste, set up 3 parallel experiments simultaneously. Escherichia coli and Pseudomonas aeruginosa by the same method. Marking the serial numbers of each group of culture dishes, sealing the edges with a proper amount of sealing films, placing the culture dishes in a constant-temperature incubator at 37 ℃ after being pasted, inverting for 24 hours, and determining the size of a bacteriostatic zone. The results of the experiment are shown in table 2.

TABLE 2 measurement results of zone of inhibition (mm) diameter

The experimental results in table 2 show that the liquid dressing of the present invention has good bacteriostatic effect on staphylococcus aureus, escherichia coli and pseudomonas aeruginosa, and the bacteriostatic effect is superior to that of the 75% ethanol solution of the positive control group. Therefore, the liquid dressing has a good inhibition effect on common infectious bacteria on wound surfaces, and can effectively reduce the incidence rate of wound infection.

Wound healing test

30 adult healthy SD rats were anesthetized by intraperitoneal injection of 30mg/kg chloral hydrate (10% by volume), shaved on the backs, and the skin was exposed. The chest part of the back is the center and is pressed by 2cm ² The size of the wound is cut to remove the whole layer of skin to deep fascia, and a square wound is formed. The postoperative rats were randomly divided into a general gauze group (blank control group), a commercially available liquid dressing group (positive control group), and a liquid dressing group according to example 1 of the present invention, 10 per group. The common gauze group is used for conventional bandaging, and the liquid dressing group is used for proper spraying. Dressing change every day after operation, observing and recording wound appearance, measuring the length and width of the wound on days 3, 5, 7, 9 and 11 after operation, and calculating the wound area and the wound healing rate (%), wherein the formula is as follows: wound healing rate (%) = (initial wound area-wound area at the time of measurement)/initial wound area × 100%. The results of the experiment are shown in table 3.

TABLE 3 wound healing test

As can be seen from the experimental results in Table 3, the liquid dressing of the present invention significantly promoted the reduction of the wound area after the operation in rats. Compared with the commercially available liquid dressing product, the liquid dressing can obviously shorten the wound healing time, the wound healing rate can reach more than 98% within 11 days after operation, is obviously superior to a positive control group and a blank control group, and can effectively prevent tissue adhesion and wound scab. Histopathological observation also shows that the liquid dressing of the invention can promote the moderate and ordered arrangement and growth of granulation tissues. In conclusion, the liquid dressing has excellent performance and good development potential, provides a new reference for selection of clinical wound dressings, and has wide market application prospect.

The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications or equivalents may be made to the technical solution without departing from the principle of the present invention, and these modifications or equivalents should also be regarded as the protection scope of the present invention.

Claims (7)

1. The liquid dressing for external wound care is characterized by comprising the following raw material components in percentage by weight: 1-2% of moxifloxacin hydrochloride, 0.3-0.8% of pseudo-heptanine, 0.2-0.4% of chlorobutanol, 2.5-3.5% of alginate, 1.2-1.8% of hyaluronic acid and derivatives thereof, 3-6% of humectant, 12-18% of film forming agent, a proper amount of pH regulator and the balance of purified water;

the alginate is selected from sodium alginate, calcium alginate or potassium alginate;

the hyaluronic acid and the derivatives thereof are selected from hyaluronic acid, sodium hyaluronate or calcium hyaluronate.

2. The liquid dressing of claim 1, which is composed of the following raw material components in percentage by weight: 1.5% of moxifloxacin hydrochloride, 0.5% of heptadecanoic acid, 0.3% of chlorobutanol, 3% of alginate, 1.5% of hyaluronic acid and derivatives thereof, 5% of humectant, 15% of film forming agent, a proper amount of pH regulator and the balance of purified water.

3. The liquid dressing of claim 1 or 2, wherein the humectant is selected from propylene glycol, glycerol, butylene glycol or polyethylene glycol.

4. The liquid dressing of claim 1 or 2, wherein the film-forming agent is polyvinyl alcohol, polyvinyl butyral or nitrocellulose.

5. The liquid dressing of claim 1 or 2, wherein the pH adjusting agent is selected from citric acid, triethanolamine or potassium bicarbonate.

6. A method of preparing a liquid dressing for external wound care according to any one of claims 1 to 5, comprising the steps of:

(1) Weighing the raw material components according to the weight percentage for later use;

(2) Adding a film forming agent into a proper amount of purified water, heating and continuously stirring to fully dissolve the film forming agent to obtain a solution I;

(3) Adding moxifloxacin hydrochloride, pseudo-ginseng acid, chlorobutanol, alginate, hyaluronic acid and derivatives thereof and a humectant into the rest purified water, and continuously stirring to fully dissolve the materials to obtain a solution II;

(4) And mixing the solution I and the solution II, adding a pH regulator, regulating the pH to 7.0 +/-0.5, sterilizing and subpackaging to obtain the liquid dressing for external wound care.

7. The production method according to claim 6, wherein the heating temperature in the step (2) is 80 to 90 ℃.