CN111166932A - Liquid wound spray dressing and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of medical dressings, and particularly relates to a liquid wound spray dressing and a preparation method thereof. The liquid wound spray dressing comprises raw material components such as silver sulfadiazine, lidocaine, chitosan, polyvinyl alcohol, ethanol, a preservative, purified water and the like. By optimally designing the types, the proportions and the preparation method of the components, the long-acting antibacterial activity and the hemostatic property of the liquid wound dressing can be improved, the invasion of pathogenic bacteria can be resisted for a long time, the ordered growth and the texture repair of wound tissues can be promoted, and the wound healing process can be accelerated. The liquid wound dressing has the advantages of definite curative effect, safe and reliable use, quick and simple preparation method, no stimulation to skin, and good practical value and popularization and application significance.

Description

Liquid wound spray dressing and preparation method thereof

Technical Field

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

Background

The wound dressing is a covering or protection layer for a wound, can replace damaged skin to obtain a temporary protection effect in the process of wound healing and treatment, avoids or controls wound infection, and provides a proper healing environment for a wounded surface. With the recent aging of the global population and the annual increase of chronic diseases, the incidence of chronic wounds is increased. With the advancement of science and technology, the clinical medical care method for wounds tends to need a more efficient care method, and the conventional dressings such as bandages, gauzes, cotton balls and the like in the past are insufficient to deal with the modern large and diversified wound conditions, so that more efficient wound healing medical materials and more suitable for the care of the dressings for the wounds with diversified diseases are clinically needed.

With the advancement of science and knowledge, various artificial materials are developed to replace the conventional dressing as the substrate of the modern dressing, and advanced dressings are produced due to inoculation. The doctor combines the traditional industrial technology of chemical material, machinery, weaving, has promoted the performance of dressing greatly and has created more diversified functions, and the development trend of future high-order dressing is also closely relevant with health care and nursing for the material design of wound dressing is not only comfortable cover wound, and has moved towards functional development, for example: aid in wound healing, medicated dressings, specialized dressings for the type of wound, and the like. But its sole goal is to achieve the ultimate goal of shortening the wound healing process and reducing wound pain. According to the statistics of Espicom Business intelligence, the worldwide wound care market value in 2007 is about $ 100 billion, with advanced wound care accounting for $ 46 billion and growing at a rate of 2 digits. According to the market survey of Frost & Sullivan, the advanced dressing market in western european countries in 2008 is about $ 15.2 billion, with an annual average compound increase rate of about 16.2%; according to the investigation of BCC Research, the advanced dressing market in the us in 2008 is about $ 35 billion, with an annual average compound increase rate of 11.3%. Since 2011, the market of advanced dressings is gradually rising upwards and further is maintained in a stable growth state, the average annual composite growth rate is maintained at 4.6%, and the market demand of advanced dressings is increased.

The existing dressing product for treating the wound is mainly suitable for nursing superficial wound surfaces such as small wound, abrasion, cut wound and the like and peripheral skin, and is often used together with other secondary dressings when large open wound is nursed. Common wound dressing products are mainly externally applied and are in the forms of paste, liquid, powder and the like. The liquid dressing is mainly characterized in that the dressing is painless when being applied and changed. The existing liquid dressing products are mainly used for preventing infection generally, rarely have the effects of resisting bacteria, stopping bleeding and promoting wound healing, and the wound healing still needs to depend on the self-repairing effect of a human body, so that the application effect of the dressing products has a great space for improving.

Disclosure of Invention

The invention aims to solve the technical problem that the existing liquid wound dressing is only used for covering and protecting a wound after film forming, and provides a liquid wound spray dressing with the functions of resisting bacteria, stopping bleeding and promoting wound healing and a preparation method thereof.

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

a liquid wound spray dressing comprises the following raw material components in percentage by weight: 0.5-2% of sulfadiazine silver, 0.2-1% of lidocaine, 0.5-4% of chitosan, 2-8% of polyvinyl alcohol, 6-20% of ethanol, 0.2-2% of preservative and the balance of purified water.

Preferably, the liquid wound spray dressing comprises the following raw material components in percentage by weight: 0.8-1.2% of sulfadiazine silver, 0.5-0.8% of lidocaine, 1-3% of chitosan, 3-6% of polyvinyl alcohol, 8-16% of ethanol, 0.5-1% of preservative and the balance of purified water.

Preferably, the liquid wound spray dressing comprises the following raw material components in percentage by weight: 1% of sulfadiazine silver, 0.7% of lidocaine, 2% of chitosan, 5% of polyvinyl alcohol, 12% of ethanol, 0.8% of preservative and the balance of purified water.

Preferably, the silver sulfadiazine is nano-powder subjected to micronization treatment, and the average particle size is 100-200 nm.

Preferably, the lidocaine is at least one selected from lidocaine hydrochloride, free base of lidocaine, lactate of lidocaine and carbonate of lidocaine, and has average particle diameter of 50-100 nm.

Preferably, the chitosan has a molecular weight of 60-80 ten thousand and a degree of deacetylation of greater than 85%.

Preferably, the polymerization degree of the polyvinyl alcohol is 1800-2000, and the alcoholysis degree is 90-96%.

Preferably, the preservative is selected from at least one of ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate and sodium benzoate.

Furthermore, the invention also provides application of the liquid wound spray dressing in preparing a medical material for surgical wounds.

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

(1) adding a proper amount of purified water into polyvinyl alcohol, soaking for 1-2 hours, heating at a constant temperature of 90-95 ℃ until the polyvinyl alcohol is dissolved, and uniformly stirring to obtain a solution A;

(2) adding chitosan into a proper amount of purified water, soaking, dispersing and dissolving to obtain a solution B;

(3) dissolving the preservative with ethanol to obtain a solution C;

(4) and sequentially adding the solution B and the solution C into the solution A, then adding the silver sulfadiazine and the lidocaine to supplement sufficient purified water, and uniformly stirring.

The sulfadiazine silver dressing not only has the broad-spectrum antibacterial action of silver ions, but also has the antibacterial action of sulfadiazine, has a strong inhibiting effect on pseudomonas aeruginosa, and simultaneously has good antibacterial action on gram-positive bacteria, gram-negative bacteria, saccharomycetes and other fungi. In addition, the silver sulfadiazine also has the function of astringency, and can dry and scab the wound surface after being applied to the affected part, thereby having better effect on controlling wound surface infection.

Lidocaine is a local anesthetic with rapid penetration and wide dispersion. The dressing embedded with lidocaine has hemostatic and analgesic effects. Because only the dressing part contacting the wound surface is dissolved and released, the local anesthetic poisoning can not occur.

The chitosan is prepared by extracting chitin as a raw material, is insoluble in water, can be dissolved in dilute acid, and can be absorbed by a human body. Chitosan is a first-order derivative of chitin, has a chemical structure of a high-molecular basic polysaccharide polymer with cations, has unique physical and chemical properties and a biological activation function, has good film forming property, air permeability and biocompatibility, generally forms a transparent semi-permeable soft film, also has the effects of resisting bacteria, diminishing inflammation, stopping bleeding, reducing wound exudation, promoting wound tissue regeneration, repair and healing, is easy to process and form, and is suitable for being used as a dressing. Through histopathological observation, under the coverage of the chitosan dressing, cells stimulate the skin layer to repair and reconstruct the tissue structure, and induce the wound surface to heal quickly and orderly to generate good new skin tissues.

The polyvinyl alcohol is white solid, and the appearance is divided into flocculent, granular and powdery; has no toxicity, odor or pollution, and can be dissolved in water of 80-90 deg.C. The aqueous solution of polyvinyl alcohol has good adhesion and film-forming property; can resist most organic solvents such as oils, lubricants, hydrocarbons and the like; has the chemical properties of long-chain polyol esterification, etherification, acetalization and the like, is easy to form a film, has excellent mechanical properties, and enhances the tensile strength of the film along with the increase of polymerization degree and alcoholysis degree to form a hard film generally. Has no toxicity, no odor, no irritation to skin, and no skin allergy. Is commonly used for preparing medical materials and cleaning products. The polyvinyl alcohol is used as a main material body, and can be used for preparing surgical wound dressings and dressings for negative pressure drainage.

Compared with the prior art, the invention has the beneficial effects that: the liquid wound dressing has the characteristics of obvious antibacterial and anti-inflammatory effects, obvious hemostatic and analgesic effects, wound healing promotion, film forming protection and the like. Through the optimal design of the proportion of the components and the preparation method, the long-acting antibacterial activity and the hemostatic activity of the liquid wound dressing can be improved, the invasion of pathogenic bacteria can be resisted for a long time, the ordered growth and the texture repair of wound tissues can be promoted, and the wound healing process can be accelerated; the formed protective film has good adhesion and adhesiveness to the wound surface, can effectively reduce resistance generated when the wound surface moves, and can resist pathogen infection for a long time. The liquid wound dressing has the advantages of definite curative effect, safe and reliable use, quick and simple preparation method, no stimulation to skin, and good practical value and popularization and application significance.

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 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.

Experiment raw materials: silver sulfadiazine is provided by Shanghai Changhai Hospital; lidocaine hydrochloride, tianjin jin Yao pharmaceutical Co., Ltd; chitosan was purchased from shanghai kungquan biotechnology limited; polyvinyl alcohol was purchased from alfa aesar chemical ltd.

Example 1

A liquid wound spray dressing comprises the following raw material components in percentage by weight: 0.8% of sulfadiazine silver, 0.5% of lidocaine hydrochloride, 3% of chitosan, 6% of polyvinyl alcohol, 10% of ethanol, 0.8% of sodium benzoate and the balance of purified water.

The preparation method of the liquid wound spray dressing comprises the following steps:

(1) adding a proper amount of purified water into polyvinyl alcohol, soaking for 1.5 hours, heating at a constant temperature of 90 ℃ until the polyvinyl alcohol is dissolved, and uniformly stirring to obtain a solution A;

(2) adding chitosan into a proper amount of purified water, soaking, dispersing and dissolving to obtain a solution B;

(3) dissolving sodium benzoate in ethanol to obtain solution C;

(4) and sequentially adding the solution B and the solution C into the solution A, then adding silver sulfadiazine and lidocaine hydrochloride, supplementing sufficient purified water, and uniformly stirring.

Example 2

A liquid wound spray dressing comprises the following raw material components in percentage by weight: 1.2% of sulfadiazine silver, 0.8% of lidocaine free alkali, 1% of chitosan, 3% of polyvinyl alcohol, 8% of ethanol, 0.6% of methyl p-hydroxybenzoate and the balance of purified water.

The preparation method of the liquid wound spray dressing is the same as that of example 1.

Example 3

A liquid wound spray dressing comprises the following raw material components in percentage by weight: 1% of sulfadiazine silver, 0.7% of lidocaine hydrochloride, 2% of chitosan, 5% of polyvinyl alcohol, 12% of ethanol, 0.8% of ethyl p-hydroxybenzoate and the balance of purified water.

The preparation method of the liquid wound spray dressing is the same as that of example 1.

Experiment of bacteriostatic effect

Referring to 2012 edition "disinfection technical specification", the liquid wound spray dressing of examples 1-3 was subjected to a microbe killing effect experiment, and a blank control group without any antibacterial agent was established while polyhexamethylene biguanide aqueous solution with a mass percentage concentration of 0.02% and iodophor disinfectant solution with a mass percentage concentration of 0.5% were used as control groups. The experimental procedure was as follows: staphylococcus aureus, pseudomonas aeruginosa, streptococcus pyogenes and candida albicans are used as test strains, and the preparation concentration is 10⁵CFU/ml bacterial suspension. 4 kinds of bacteria solutions were respectively dipped in sterilized cotton swabs and soaked in the liquid wound spray dressing of examples 1 to 3, a phenoxyethanol aqueous solution with a mass percentage concentration of 0.05% and a polyhexamethylene biguanide aqueous solution with a mass percentage concentration of 0.02% for 30 min. Then, 0.5ml of the above test liquid was spread on a sterile plate containing beef extract peptone medium (Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes) and potato agar medium (Candida albicans), cultured for 48h, 72h, and the colony count was performed, and the bacteriostatic ratio was calculated from the colony count of the blank group. The results of the experiment are shown in table 1.

TABLE 1 experiment of bacteriostatic effect (bacteriostatic rate) of liquid wound spray dressing

The experimental results in table 1 show that the liquid wound spray dressing of the present invention has a good microorganism killing effect, the killing rate of staphylococcus aureus, pseudomonas aeruginosa, streptococcus pyogenes and candida albicans is above 98%, and the sterilization effect is superior to that of the control group which contains 0.02% polyhexamethylene biguanide aqueous solution and 0.5% iodophor disinfectant. The results prove that the liquid wound spray dressing has a wide antibacterial spectrum, can effectively inhibit the growth of microorganisms, reduce the incidence rate of wound infection, and can be better suitable for long-acting antibacterial protection of open wounds such as skin mucosa, mechanical injury, operation incision and the like.

Hemostasis test

40 rabbits weighing 5kg were selected and randomly divided into 4 groups of 10 rabbits each, which corresponded to the liquid wound spray dressing of examples 1-3 and the commercially available wound antibacterial spray dressing (chuanling brand, main ingredient was chitosan solution), respectively. Fixing white rabbit on dissecting table, performing anesthesia, performing laparotomy layer by layer, sucking tissue fluid and blood on abdominal cavity and abdominal wall with sterile gauze, and exposing liver. A wound of 0.8cm x 0.5cm was prepared on the lobe of the liver, and during the formation of the wound, bleeding was first absorbed with sterile medical gauze, and then the liquid wound spray dressing of examples 1-3 and commercially available wound antibacterial spray dressings were sprayed onto the wound (about 5-8cm from the wound), covered with sterile gauze if necessary, timed with a stopwatch, and the hemostatic effect was observed, and after complete hemostasis, the hemostatic time was recorded.

TABLE 2 hemostasis test (time, s)

	Example 1	Example 2	Example 3	Control group
					Time of hemostasis	8.6±0.4s	8.9±0.5s	8.2±0.4s	13.1±0.5s

The experimental results in table 2 show that the liquid wound spray dressing of the present invention has a more excellent hemostatic effect, and the hemostatic time is significantly shorter than that of the similar commercially available products, so as to achieve a rapid hemostatic effect.

Wound healing test

40 SD rats were selected, randomly divided into 4 groups of 10 each, corresponding to the liquid wound spray dressings of examples 1-3 and commercially available wound antibacterial spray dressings (Chuanling brand, main ingredient is chitosan solution), respectively. Each rat was anesthetized with 1.5ml/kg by intraperitoneal injection of 10% chloral hydrate, and after removal of the dorsal hairs, the skin was sterilized. An area of 1.5cm was cut at the back of each rat²Full thickness wounds of size. Then, the liquid wound spray dressing of examples 1-3 and a commercially available wound antibacterial spray dressing were sprayed onto the wound surface (about 5-8cm from the wound surface), and the wound was locally sprayed once in the morning and evening each day, and the wound healing of rats was observed on days 3, 6, 9, and 12 after spraying, respectively. The wound length and width were measured and the wound area and the wound healing rate were calculated as (initial wound area-measured wound area on day n)/initial wound area x 100%, with the experimental results shown in table 3.

TABLE 3 test of the healing promotion of liquid wound spray dressing on rat wounds

As can be seen from the test results in Table 3, the liquid wound spray dressing of the present invention has a significant healing promoting effect on the wounds of rats. Compared with the commercially available wound antibacterial spray dressing, the liquid wound spray dressing can obviously shorten the wound healing time, has the wound healing rate of over 93 percent within 12 days, is obviously superior to a control group, further realizes the rapid healing of the wound, and can promote the rapid and ordered growth of the new tissue of the wound. The liquid wound spray dressing has the advantages of definite curative effect, safe and reliable use, no stimulation to skin, good film-forming property, capability of promoting wound healing while protecting the wound and resisting the invasion of pathogenic bacteria for a long time, and good practical value and popularization and application significance.

The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (10)

1. The liquid wound spray dressing is characterized by comprising the following raw material components in percentage by weight: 0.5-2% of sulfadiazine silver, 0.2-1% of lidocaine, 0.5-4% of chitosan, 2-8% of polyvinyl alcohol, 6-20% of ethanol, 0.2-2% of preservative and the balance of purified water.

2. The liquid wound spray dressing of claim 1, comprising the following raw material components in percentage by weight: 0.8-1.2% of sulfadiazine silver, 0.5-0.8% of lidocaine, 1-3% of chitosan, 3-6% of polyvinyl alcohol, 8-16% of ethanol, 0.5-1% of preservative and the balance of purified water.

3. The liquid wound spray dressing of claim 2, comprising the following raw material components in percentage by weight: 1% of sulfadiazine silver, 0.7% of lidocaine, 2% of chitosan, 5% of polyvinyl alcohol, 12% of ethanol, 0.8% of preservative and the balance of purified water.

4. The liquid wound spray dressing of any one of claims 1-3, wherein the silver sulfadiazine is a micronized nanopowder having an average particle size of 100-200 nm.

5. The liquid wound spray dressing of any one of claims 1-3, wherein the lidocaine is selected from at least one of lidocaine hydrochloride, lidocaine free base, lidocaine lactate, lidocaine carbonate, and has an average particle size of 50-100 nm.

6. The liquid wound spray dressing of any one of claims 1-3, wherein the chitosan has a molecular weight of 60-80 ten thousand and a degree of deacetylation of greater than 85%.

7. The liquid wound spray dressing of any one of claims 1-3, wherein the degree of polymerization of the polyvinyl alcohol is 1800-2000 and the degree of alcoholysis is 90-96%.

8. The liquid wound spray dressing of any one of claims 1-3, wherein the preservative is selected from at least one of ethyl paraben, methyl paraben, sodium benzoate.

9. Use of a liquid wound spray dressing according to any one of claims 1 to 8 in the preparation of a surgical wound dressing medical material.

10. The method of making a liquid wound spray dressing according to any one of claims 1-8, comprising the steps of:

(1) adding a proper amount of purified water into polyvinyl alcohol, soaking for 1-2 hours, heating at a constant temperature of 90-95 ℃ until the polyvinyl alcohol is dissolved, and uniformly stirring to obtain a solution A;

(2) adding chitosan into a proper amount of purified water, soaking, dispersing and dissolving to obtain a solution B;

(3) dissolving the preservative with ethanol to obtain a solution C;

(4) and sequentially adding the solution B and the solution C into the solution A, then adding the silver sulfadiazine and the lidocaine to supplement sufficient purified water, and uniformly stirring.