CN106620831B

CN106620831B - Dressing for nursing skin ulcer

Info

Publication number: CN106620831B
Application number: CN201611199965.3A
Authority: CN
Inventors: 石佳明
Original assignee: Hainan Zhuorei Biomedical Co ltd
Current assignee: Hainan zhuorei biomedical Co.,Ltd.
Priority date: 2016-12-22
Filing date: 2016-12-22
Publication date: 2020-08-04
Anticipated expiration: 2036-12-22
Also published as: CN106620831A

Abstract

The application provides a dressing for treating skin ulcer, which contains the following components of the spinosad and nicotinamide. The dressing also contains hyaluronic acid, soluble silver salt, alginate and chitosan. The dressing can enhance local blood circulation and promote healing of skin ulcer, and particularly can promote healing of diabetic foot ulcer.

Description

Dressing for nursing skin ulcer

Background

Skin ulcer is a common disease and a frequently encountered disease in clinic. The main reasons of the burn are burns, chemical burns or skin trauma infection and long-term compression. It is commonly found in the elderly, and often combined with varicose veins of lower limbs, chronic eczema, heart disease, diabetes, etc. Ulcers can be delayed or recurrent due to topical skin dystrophies or improper treatment, which can cause inconvenience to the patient.

Diabetic Foot (DF) is a pathological condition of tissue destruction in the foot or lower limb of diabetic patients, and is a common consequence of the development of peripheral vascular and neuropathy. The most common clinical manifestation of diabetic feet is a group ulcer. Ulcers can affect the skin, subcutaneous tissue, muscle, bone. Diabetic foot ulcers are one of the serious complications of diabetes and are the main cause of disability and death of diabetic patients. Diabetic foot ulcers often involve multiple pathogenesis, mainly due to local blood perfusion deficiency caused by diabetes combined with large, small, microvascular lesions, peripheral neuropathy and mechanical injury combined with infection. Generally, treatment of ulcers in the diabetic group includes control of hyperglycemia, hyperlipidemia, and hypertension; relieving local pressure on the affected part; using antithrombotic and lower limb blood circulation improving medicines; the use of anti-inflammatory drugs; and a hyperbaric oxygen chamber. When a diabetic foot ulcer develops into a deep infection or gangrene, amputation is often necessary to prevent further spread of the infection, endangering the patient's life. Currently, there is a lack of topically effective drugs that are effective in treating diabetic foot.

Mangrove ecosystems are one of the most diverse and productive marine ecosystems in the world, mangrove swamp area has abundant plant material, abundant planktonic algae and planktonic organisms, and these conditions are well suited for the reproduction of microorganisms, during the last decade mangrove habitats have been proven to be an abundant source of new species of fungi, which form the second major ecological subclass of marine fungi, cochleariae is a red pigment, which was first isolated from bostryconeem asperescation (Tetrahedron L et.58: 6087,1968; Tetrahedron L et.58: 567; Tetrahedron 26:1339,1968), which inhibits gram positive bacteria, which was subsequently reported to be isolated from Nigrospora oryzae (sank kenkyyuo neo: 165,1969), ngus artherospora (exothermium), which was subsequently reported to have the effect of inhibiting activity of spore growth of spore in vitro bacillus strain # 3643, which was also reported to have the activity of intracellular spore growth inhibiting activity of spore in the wild ginger strain # 3623, 7: 31, 7, 31, 23, and so many further experiments on the bacterial strains of echinococcus strain.

Nicotinamide is a component of both coenzyme I and coenzyme II, known as the coenzymes of many dehydrogenases. The deficiency can affect normal respiration and metabolism of cells to cause pellagra. Nicotinamide is easily absorbed through gastrointestinal tract, distributed to the tissues of the whole body, metabolized by the liver, and discharged from urine in small amount, and can be used for supplementing nutrition and treating dermatitis and glossitis.

It is well known that a problem faced by caregivers when selecting a wound dressing for treating a wound is to provide the wound with an advantageous healing environment while treating chronic wound exudate, which includes absorption of wound exudate and maintenance of wound moisturization, while effectively inhibiting microbial growth of the wound. The wound active repairing material can stimulate epidermal cells and form fibrocyte migration, reduce the circulation resistance of newly-regenerated repaired blood vessels, block the deposition of granulocytes, inhibit the swelling of vascular endothelium, reduce the accumulation of cell debris in blood vessels, and greatly reduce the blood resistance and embolism incidence rate of micro blood vessels, thereby playing a role in improving local microcirculation and repairing tissues, having the function of promoting the growth of blood vessels, and being used for treating wounds with little effusion, mechanical trauma and contusion, diabetic ulcer, bedsore, pressure ulcer, skin and mucosa ulcer, erosive lesion, local burn and scald, wounds caused by various operations and trauma, operation incisions with delayed healing and wounds difficult to heal caused by unknown reasons.

Chinese patent application 01122949.7 discloses a novel biological dressing, in particular a chitosan biological fluid dressing film for human skin wound, burn and body surface ulcer and a preparation method thereof. It uses chitosan as main raw material, and adopts the processes of acidolysis, adding gelatin and glycerine, neutralizing with sodium bicarbonate and filtering so as to provide a biological compatibility product. The product is easy to have acid residue, and the neutralization and filtration are complex in equipment and process.

Chinese patent application 200810039461.4 discloses a gelatin/bioactive glass composite sponge dressing and a preparation method thereof. According to the method, gelatin is used as a raw material to prepare a solution with the content of 1-30%, and the bioactive glass powder is added, so that the process time is long, freeze drying is required, the energy consumption is high, and large-scale production is not facilitated. The dressing with the main carrier component of the gelatin is also hardened by volatile water in use, so that the contact comfort of the wound surface is reduced.

Detailed Description

The application provides a nursing dressing for skin ulcer, which is characterized by comprising an active ingredient and an auxiliary material. The active ingredients of the invention include spinosad and nicotinamide. The dressing also comprises hyaluronic acid or salt thereof, soluble silver salt, alginate, chitosan and the like as auxiliary materials.

The care dressing described herein, wherein the active ingredient is present in an amount of 0.1% to 1.5%, preferably 0.5% to 1% by weight of the total weight of the dressing.

The structural formula of the spinosad described in the application is as follows:

in the active ingredients described herein, the ratio of spinosad to nicotinamide is 1:1 to 1:9, preferably 1:2.5 to 1:8.

In the auxiliary material used in the dressing for nursing care, hyaluronic acid or salt thereof simultaneously contains high molecular weight hyaluronic acid and low molecular weight hyaluronic acid, wherein the molecular weight of the high molecular weight hyaluronic acid or salt thereof is 100-280 ten thousand daltons, preferably 120-180 ten thousand daltons; the molecular weight of the low molecular weight hyaluronic acid or the salt thereof is 0.5-40 ten thousand daltons, preferably 0.5-30 ten thousand daltons.

In the auxiliary materials, the hyaluronate is sodium salt.

In the dressing described herein, the soluble silver salt is silver nitrate.

In the auxiliary material, the content of high molecular weight hyaluronic acid or salt thereof accounts for 0.05-12% of the total weight of the dressing, the content of low molecular weight hyaluronic acid or salt thereof accounts for 0.5-12%, the content of soluble silver salt accounts for 0.005-2%, the content of alginate accounts for 3-20%, and the content of chitosan accounts for 0.1-20%.

In the auxiliary material, the content of high molecular weight hyaluronic acid or salt thereof accounts for 0.5-8% of the total weight of the dressing, the content of low molecular weight hyaluronic acid or salt thereof accounts for 0.9-7%, the content of soluble silver salt accounts for 0.005-1%, the content of alginate accounts for 4-15%, and the content of chitosan accounts for 0.9-10%.

The auxiliary materials of the application can also contain 3% -8% of polyethylene glycol, propylene glycol or glycerin, and the balance is water.

The nursing dressing can be prepared into gel, the gel can be subjected to blade coating, drying, curing to form a film, cutting (cutting according to specification and size), and the obtained composite film is covered with materials such as foam, non-woven fabric or fiber cotton, so that a dressing product with enhanced adsorbability and improved tensile strength of the film is obtained.

It is an object of the present application to provide a dressing for the treatment of skin ulcers. The applicant unexpectedly found that the spinosad can enhance local blood circulation and promote wound healing, and can achieve better effect of treating skin ulcer together with nicotinamide, especially skin ulcer caused by diabetes.

Another aspect of the present application is to provide a dressing adjuvant composition in which high molecular weight and low molecular weight hyaluronic acid are used in combination to exert multiple effects. The high molecular weight hyaluronic acid has excellent viscoelasticity, moisture retention and water absorption, can provide proper year and adhesion for the gel preparation, and ensures the form of the gel. The low molecular weight hyaluronic acid has certain moisturizing performance, can promote angiogenesis, remove excessive free radicals, reduce oxidative damage of cells, and is easier to permeate into the deep layer of the skin. The two can play an auxiliary role in wound healing when being used together. In addition, the chitosan, alginate and silver nitrate are compatible, soluble silver salt in the obtained matrix can play a role in disinfection and sterilization, the chitosan can further accelerate the regeneration and recovery of skin, and a certain bacteriostatic effect is achieved.

Another aspect of the present application is to provide a method for preparing the dressing for treating skin ulcer, which comprises putting the spinosad in water for ultrasonic emulsification and dispersion, then weighing the high molecular weight hyaluronic acid, the low molecular weight hyaluronic acid, the alginate and the chitosan, putting the weighed materials in water for stirring, and then adding the polyethylene glycol, the dispersion of the spinosad and the nicotinamide and the silver nitrate into the mixture in turn. Fully and uniformly stirring the mixture, and adding water to complement 1000g to obtain the gel dressing. If necessary, the obtained gel can be subjected to blade coating, low-temperature drying, curing and film forming, cutting (cutting according to the specification and size), and the obtained composite film is covered with non-woven fabric to obtain the patch.

Another aspect of the present application is to provide a use of a combination of spinosad and nicotinamide for preparing a dressing for treating skin ulcers, especially diabetic foot ulcers, wherein the dressing further comprises high molecular weight hyaluronic acid and low molecular weight hyaluronic acid in the adjuvant.

Preparation example 1

1) 0.5g of spinosad was weighed and put into a small amount of water for ultrasonic emulsification.

2) 100g of high molecular weight sodium hyaluronate, 50g of low molecular weight sodium hyaluronate, 30g of alginate and 8g of chitosan are weighed and put into water to be stirred.

3) Weighing 30g of polyethylene glycol, adding the solution obtained in the step 2), and stirring uniformly.

4) Adding 3) into the mixture obtained in the step 1), weighing 0.5g of nicotinamide and 0.05g of silver nitrate, adding the mixture and stirring.

5) Adding water to 1000g, and stirring to obtain gel.

Preparation example 2

1) 2g of the streptoverticillium was weighed and put into a small amount of water for ultrasonic emulsification.

2) 80g of high molecular weight sodium hyaluronate, 70g of low molecular weight sodium hyaluronate, 45g of alginate and 20g of chitosan are weighed and put into water to be stirred.

4) Adding 3) into the mixture obtained in the step 1), weighing 10g of nicotinamide and 0.05g of silver nitrate, adding the mixture and stirring.

5) Adding water to 1000g, and stirring to obtain gel.

Preparation example 3

1) 3g of the streptoverticillium was weighed and put into a small amount of water for ultrasonic emulsification.

2) 120g of high molecular weight sodium hyaluronate, 50g of low molecular weight sodium hyaluronate, 100g of alginate and 60g of chitosan are weighed and put into water to be stirred.

3) Weighing 40g of glycerol, adding the solution obtained in 2), and stirring.

4) Adding 3) into the mixture obtained in the step 1), weighing 7.5g of nicotinamide and 0.05g of silver nitrate, adding the mixture and stirring.

5) Adding water to 1000g, and stirring to obtain gel.

Preparation example 4

1) 7.5g of the streptostacin are weighed and put into a small amount of water for ultrasonic emulsification.

2) 120g of high molecular weight sodium hyaluronate, 50g of low molecular weight sodium hyaluronate, 80g of alginate and 80g of chitosan are weighed and put into water to be stirred.

3) Weighing 40g of glycerol, adding the solution obtained in 2), and stirring.

5) Adding water to 1000g, and stirring to obtain gel.

Comparative example 1

1) Weighing 120g of high molecular weight sodium hyaluronate, 50g of low molecular weight sodium hyaluronate, 80g of alginate and 80g of chitosan, and putting the materials into water for stirring.

2) Weighing 40g of glycerol, adding the solution obtained in 1), and stirring.

3) Adding water to 1000g, and stirring to obtain gel.

Comparative example 2

3) Weighing 40g of glycerol, adding the solution obtained in 2), and stirring.

4) Adding 3) into the mixture obtained in 1), weighing 0.05g of silver nitrate, adding into the mixture and stirring.

5) Adding water to 1000g, and stirring to obtain gel.

Comparative example 3

2) Weighing 40g of glycerol, adding the solution obtained in 1), and stirring.

3) Weighing 7.5g of nicotinamide and 0.05g of silver nitrate, adding into the mixture in the step 2), and stirring.

4) Adding water to 1000g, and stirring to obtain gel.

Detailed Description

Experiment I, treatment effect on diabetic foot ulcer

1, preparing a diabetes animal model:

rats were male SD rats, SPF grade, body weight (180. + -. 10) g. After 8 weeks of high-fat diet feeding, a rat model of type II diabetes was obtained by left lower abdominal injection of 1.5% streptozotocin dissolved in citric acid-sodium citrate buffer solution of pH 4.5 at a dose of 35 mg/kg. The preparation method of the high-fat feed comprises the following steps: firstly, stirring and mixing 15% of barley, 31% of wheat, 15% of corn, 15% of bran and 6% of fish meal uniformly according to a proportion, adding bean pulp, oil and salt, uniformly mixing, and then pressing and forming to prepare a base feed, and then stirring and mixing 73% of the base feed, 20% of lard, 2% of milk powder, 1% of cholesterol and 4% of cane sugar uniformly according to a proportion, and then pressing and forming to prepare the high fat feed.

2, diabetic scald ulcer model:

taking the rat in the 1, carrying out intraperitoneal injection anesthesia on the rat by using 45mg/kg pentobarbital sodium, depilating the back by using a depilatory, scalding the deep II-degree scald wound surface with the diameter of 1.8cm on the back by using a scald instrument, wherein the scald conditions are as follows: the temperature of the ironing head is 85 ℃; the pressure 0.5kg time was 10 seconds. Exposing the wound surface without binding, and feeding in a single cage after numbering.

3, grouping experimental animals:

a first group: physiological saline

Second group: comparative example 1 gel

Third group: comparative example 2 gel

And a fourth group: comparative example 3 gel

And a fifth group: preparation example 4 gel preparation

A sixth group: preparation example 3 gel

A seventh group: preparation example 2 gel

Each group consisted of 5 mice, administered 1 time daily for 18 consecutive days. The treatment is started on the day after the wound surface is formed, hydrogen peroxide and normal saline are used for washing the wound and iodophor is used for disinfecting the wound surface before the treatment, and then 0.2ml of corresponding medicine is used and is uniformly coated by a cotton swab.

4, determination of the therapeutic effect on scalded injury:

all experimental animals have dry wound surfaces without exudation and festering phenomena from the day of wound surface formation to the end of treatment, and as can be seen from table 1, the drug-loaded gel has a good treatment effect on the scald skin injury of type II diabetic SD rats, and the wound areas of all groups are gradually reduced and are dose-dependent along with the extension of treatment time from the time of wound surface formation (day 0).

Table 1, therapeutic action of the gel of the present application on type II diabetes SD rat skin scald injury (mean + -SD)

Experiment two, treatment effect on skin injury caused by trauma

1, preparation of animal model

Selecting male SD rat with weight of 180-²The fresh wound surface. The wound surface is pressed to stop bleeding, exposed for treatment, numbered and raised in a single cage, and the common mice can freely take the food.

2, grouping experimental animals:

a first group: physiological saline

Second group: comparative example 1 gel

Third group: comparative example 2 gel

And a fourth group: comparative example 3 gel

And a fifth group: preparation example 4 gel preparation

A sixth group: preparation example 3 gel

A seventh group: preparation example 2 gel

Each group consisted of 5 mice, administered 1 time daily for 14 consecutive days. The treatment is started on the day after the wound surface is formed, hydrogen peroxide and normal saline are used for washing the wound and iodophor is used for disinfecting the wound surface before the treatment, and then 0.2ml of corresponding medicine is used and is uniformly coated by a cotton swab.

3, determination of the therapeutic action on traumatic injury

All experimental animals have dry wound surfaces without exudation and festering phenomena from the day of wound surface formation to the end of treatment, and as can be seen from table 2, the drug-loaded gel has a good treatment effect on SD rat traumatic skin injury, and the wound areas of all groups are gradually reduced and are dose-dependent along with the prolonging of treatment time from the time of wound surface formation (0 day).

TABLE 2 therapeutic effect of the gels of the present application on traumatic injury of skin of SD rats (mean + -SD)

Claims

1. A dressing for nursing skin ulcer contains active ingredients and auxiliary materials, wherein the active ingredients comprise spinosad and nicotinamide, the ratio of the spinosad to the nicotinamide is 1:1, and the auxiliary materials comprise high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, soluble silver salt, alginate and chitosan; wherein the molecular weight of the high molecular weight hyaluronic acid is 100-280 ten thousand daltons, and the molecular weight of the low molecular weight hyaluronic acid is 0.5-40 ten thousand daltons; wherein the soluble silver salt is silver nitrate; the total weight of the dressing is 0.1% -1.5% of the total weight of the Sporothrin and the nicotinamide, the content of the high molecular weight hyaluronic acid is 0.05% -12% of the total weight of the dressing, the content of the low molecular weight hyaluronic acid is 0.5% -12%, the content of the soluble silver salt is 0.005% -2%, the content of the alginate is 3% -20%, the content of the chitosan is 0.1% -20%, and the content of the polyethylene glycol is 3% -8%, wherein the Sporothrin has the following structure:

。

2. a method for preparing the dressing of claim 1, wherein the gel dressing is prepared by putting the gelonin into water for ultrasonic emulsification and dispersion, then weighing the high molecular weight hyaluronic acid, the low molecular weight hyaluronic acid, the alginate and the chitosan, putting the weighed materials into water for stirring, then adding the polyethylene glycol, the dispersion liquid of the gelonin, the nicotinamide and the silver nitrate into the mixture in sequence, fully stirring, adding water to supplement 1000 g.