WO2012092812A1

WO2012092812A1 - Anti-bacterial, moisture absorptive and calcium ion donating wound dressing

Info

Publication number: WO2012092812A1
Application number: PCT/CN2011/084370
Authority: WO
Inventors: 王晓东; 张大伟; 史福军
Original assignee: 佛山市优特医疗科技有限公司; 南方医科大学珠江医院
Priority date: 2011-01-05
Filing date: 2011-12-21
Publication date: 2012-07-12
Also published as: CN102580135A; CN102580135B

Abstract

An anti-bacterial, moisture absorptive and calcium ion donating wound dressing and a preparation method therefor. The wound dressing comprises chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers. The preparation method comprises blending chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers to obtain a fabric, cutting, packaging, and sterilizing. The wound dressing is useful in treatment of venous stasis ulcers, pressure ulcers, diabetic foot ulcers and other chronic ulcers.

Description

Wound dressing with bacteriostatic, hygroscopic and contribution to calcium ions

The present invention relates to a wound dressing comprising chitosan fibers, calcium alginate fibers and chemically modified cellulosic fibers. In particular, the present invention relates to a wound dressing which is a blend of chitosan fibers, chemically modified cellulosic fibers and seaweed fibers, and combines the superior effects of the three fibers on wound healing. The invention also relates to the use of wound dressings for chronic wounds such as venous venous ulcers, pressure ulcers and diabetic foot ulcers, as well as other chronic ulcers. Background technique

It is well known that one of the challenges that caregivers face when selecting wound dressings to treat wounds is to provide a wound healing environment while treating the chronic wound exudate. These favorable environmental conditions include, but are not limited to, inhibiting microbial growth. And can provide calcium ions.

Chitosan fibers have bacteriostatic effects, in which the positive charge of the NH ₂ group of chitosan binds to the negative charge of the bacterial cell wall, thereby inhibiting bacterial growth. In addition, small molecule chitosan penetrates into the cell wall to inhibit enzyme formation. This is easily observed in a general bacteriostatic test. When the chitosan nonwoven fabric sample was placed on a petri dish coated with bacteria for 24 hours, it was observed that the area under the nonwoven fabric was "clean", that is, in the shell. There is no bacterial growth in the area of the non-woven fabric, and the growth of the bacteria can be observed in the non-chitosan nonwoven fabric, indicating that the chitosan fiber has a bacteriostatic effect. Therefore, chitosan dressings are often used to infect wounds or wounds at risk of infection.

Wound dressings which are generally bacteriostatic in the art also include silver-containing wound dressings, but such wound dressings are clearly toxic.

A hygroscopic dressing made of carboxymethylcellulose fibers is disclosed in EP 0 690 344 and US Pat. No. 3,589, 364. WO 2010/061225 discloses a process for modifying cellulose fibers by forming water-insoluble mercaptosulfonated fibers. It has always been used to improve moisture absorption. According to the above disclosure, it is known that cellulose fibers subjected to a specific chemical treatment have a strong hygroscopicity.

It is known that seaweed fiber can release calcium ions when it absorbs wound secretion. It is a kind of functional medical dressing published by Qin Yiming (Textile Industry Press, 2007.02, 125 pages). Calcium alginate dressings can release calcium ions up to 560 mg/kg in solution A. Collins F, Hampton S and White R et al. (Collins F, Hampton S, White R (2002) AZ Dictionary of Wound Care. Mark Allen Publishing Ltd., Dinton Wiltshire) also reported on the ability of calcium ions to promote wound healing.

Calcium alginate dressings also absorb wound exudates, but their absorption is not as high as that of chemically modified cellulosic fibers.

Both EP 0 740 554 and US 647 1982 disclose a fiber dressing obtained by blending a gellable fiber such as a seaweed fiber with a conventional non-gel fiber such as cellulose fiber. The production cost of the fiber dressing can be reduced by the above method.

U.S. Patent 7,385,101 discloses a wound dressing blended with silver coated nylon fibers and absorbent fibers which are commonly used in the treatment of wound wounds.

No. 5,836,970 describes a wound dressing made of a mixture of chitosan and alginic acid fibers. Chitosan is disclosed in this patent application as having bacteriostatic and hemostatic properties and alginate fibers having moderate hygroscopicity.

US 6458460, EP0927013 and CN1303355 respectively describe a wound dressing which is a mixture of two gel fibers, one of which is carboxymethylcellulose fiber and the other is alginate fiber, which promotes moisture absorption and absorption. The best effect of wound exudate.

EP 1318842 discloses a wound dressing comprising a silver-binding fiber as a first fiber and a silver-free fiber as a second fiber. The dressing has both bacteriostatic and hygroscopic properties.

CN 1313416 discloses a method of blending cotton fibers and chitosan fibers. Although the object of the invention is not wound care, it is disclosed that the product obtained by the above blending has a certain bacteriostatic effect.

It is therefore known in the art that chitosan fibers, chemically modified cellulosic fibers and calcium alginate fibers can be used alone or in combination in chronic wound care and each has corresponding bacteriostatic, high in clinical applications. Hygroscopicity and the provision of calcium ions. However, the inventors have noted that prior art wound dressings have typically been formed from two fibers at the same time, and it has not been possible to simultaneously apply a dressing formed from the above three fibers to the same wound. There is therefore still a need for wound dressings that provide optimal healing conditions for chronic wounds. Summary of the invention The present invention relates to a wound dressing characterized in that the wound dressing comprises chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers. In particular, the present invention relates to a wound dressing which is uniformly blended with chitosan fibers, chemically modified cellulose fibers and calcium alginate fibers, and combines the respective advantages of the three fibers for wound healing, thereby being chronic Wound healing provides an optimal healing condition. The invention also relates to the use of such wound dressings for the treatment of chronic wounds.

In particular, the present invention relates to a wound dressing comprising from 5 to 90% by weight of chitosan fibers, from 5 to 90% by weight of calcium alginate fibers and from 5 to 90% by weight of chemically modified cellulose The fiber is blended, based on the total weight of the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber.

The present invention also relates to the provision of bacteriostatic, calcium ion supply and hygroscopicity to wound dressings by blending chitosan fibers, chemically modified cellulosic fibers and calcium alginate fibers at a certain ratio.

The present invention has the following advantages over the prior art:

In the wound dressing of the present invention obtained by blending three kinds of fibers, the antibacterial action of the chitosan fiber is prominent, and the chemically modified cellulose fiber has good hygroscopicity, is easy to form a hydrogel, and is gelatinized and transparent, seaweed. Calcium acid fibers mainly contribute to calcium ions. Compared to the prior art, the dressing of the present invention, which combines three advantageous functions, can simultaneously meet the requirements of a wound healing environment.

In particular, a wound dressing obtained by blending chitosan fibers, chemically modified cellulose fibers, and calcium alginate fibers achieves three advantageous functions while being compared to a single fiber or a blend of either fiber, and also the dressing itself. Provides the best wet strength.

In addition, in view of different states or stages of the wound, in particular, the wound dressing of the present invention can adjust the ratio of the superior functions of the three dressings according to the needs of the healing environment, and flexibly and accurately exert the combined effect of the wound dressing of the present invention. . DRAWINGS

Figure 1 shows the zone of inhibition of the wound dressing of Example 1 after 2, 3, and 8 days in a B. subtilis culture dish.

2 is a graph showing the release ability and time change of calcium ions of the wound dressing of Example 1. Figure 3 shows the zone of inhibition of the wound dressing of Example 4 after 2, 3, and 8 days in a B. subtilis culture dish. 4 is a graph showing the release ability and time change of calcium ions of the wound dressing of Example 4. Figure 5 shows the zone of inhibition of the wound dressing of Example 7 after 2, 3, and 8 days in B. subtilis culture dishes.

Fig. 6 is a graph showing the release ability and time change of calcium ions of the wound dressing of Example 7. detailed description

In a specific embodiment of the present invention, chitosan fibers, chemically modified cellulose fibers, and calcium alginate fibers can be separately produced by respective production methods. Calcium alginate fibers are prepared by extruding sodium alginate into a calcium solution. Preferably, the calcium alginate fiber is selected from the group consisting of high M type alginic acid, high G type alginic acid or M/G mixed alginic acid. Chitosan fibers are prepared by extruding a polymer solution into a NaOH solution. Chemically modified cellulose fibers are prepared by reacting the relevant solutions for each process. Preferably, the chitosan fibers are subjected to a chemical modification process by, for example, carboxymethylation and acylation. Preferably, the chemically modified cellulose fibers are selected from the group consisting of carboxymethyl cellulose fibers, preferably solvent-spun cellulosic fibers or insoluble water-based cellulose sulfonated fibers by carboxymethylation.

In a specific embodiment of the present invention, the mixing of the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber may be carried out before the nonwoven fabric process or in the nonwoven fabric process. Fiber mixing is usually carried out during the fiber opening stage. After the fiber opening stage, the mixed fibers are carded and then passed into a nonwoven manufacturing process, such as needle punched nonwovens.

In still another embodiment of the present invention, a surfactant may be added to the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber of the present invention to facilitate subsequent processing.

In a particular embodiment of the invention, the content of chitosan fibers, chemically modified cellulosic fibers and calcium alginate fibers depends on the ultimate requirements and function of the wound dressing. The content of the chitosan fibers is from 5 to 90% by weight based on the total weight of the chitosan fibers, the chemically modified cellulose fibers and the calcium alginate fibers. The content of the chemically modified cellulose fibers is from 5 to 90% by weight based on the total weight of the chitosan fibers, the chemically modified cellulose fibers and the calcium alginate fibers. The calcium alginate fiber is contained in an amount of from 5 to 90% by weight based on the total mass of the chitosan fiber, the chemically modified cellulose fiber and the calcium alginate fiber.

Preferably, the present invention relates to a wound dressing which is uniformly blended with 45% by weight of chitosan fibers, 50% by weight of chemically modified cellulose fibers and 5% by weight of calcium alginate fibers. Made. The wound dressing can suitably supply calcium ions, but has better hygroscopic function and bacteriostasis.

Preferably, the present invention relates to a wound dressing which is uniformly blended with 33.33 wt% of chitosan fibers, 33.33 wt% of chemically modified cellulose fibers, and 33.33 wt% of calcium alginate fibers. The wound dressing can be balanced to have the ability to provide calcium ions, better moisture absorption and bacteriostatic properties.

More preferably, any one of chitosan fibers, chemically modified cellulosic fibers, and calcium alginate fibers may be selected to 50% by weight, or 60% by weight, or even 90, depending on the final performance requirements of the desired wound dressing. weight%.

In one embodiment of the invention, the chitosan fiber is present in an amount of 5% by weight, the calcium alginate fiber is present in an amount of 5% by weight and the chemically modified cellulosic fiber is present in an amount of 90% by weight. Preferably, the content of the chitosan fiber is 10% by weight, the content of the calcium alginate fiber is 10% by weight, and the content of the chemically modified cellulose fiber is 80% by weight. More preferably, the content of the chitosan fiber is 25% by weight, the content of the calcium alginate fiber is 25% by weight, and the content of the chemically modified cellulose fiber is 50% by weight.

More preferably, in the wound dressing of the present invention, when the content of any of the materials is determined, the ratio of the other two materials is preferably controlled to be between 1:1 and 1:18. For example, after the content of chitosan in the dressing is determined, the ratio of calcium alginate fiber to chemically modified cellulose fiber is 1:1 to 1:18; or after the content of calcium alginate in the dressing is determined, chitosan fiber The ratio of the calcium alginate fiber to the chitosan fiber is from 1:1 to 1:18 when the ratio of the chemically modified cellulose fiber is from 1:1 to 1:18 or the chemically modified cellulose fiber content in the dressing is determined.

In the present invention, the linear density and length of the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber are appropriately controlled to suit the production process of the dressing. The linear density of the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber is 0.5 to 5 dtex, preferably 2 to 4 dtex, respectively. The length of the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber are 10 to 125 mm, respectively.

On the other hand, the chitosan fiber, the chemically modified cellulose fiber, and the calcium alginate fiber of the wound dressing of the present invention each contained 1% by weight of Tween 20 as a surfactant. Further, one or both of chitosan fibers, chemically modified cellulose fibers and calcium alginate fibers of the wound dressing of the present invention contain 1% to 5% by weight of PHMB or nanosilver as a bacteriostatic agent. . The present invention also relates to a wound dressing comprising any two of the chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers and non-sol fibers. In other words, any of the chitosan fibers, calcium alginate fibers, and chemically modified cellulose fibers in the wound dressing is replaced by non-sol fibers to enhance the strength of the wound dressing. The non-sol fibers are viscose fibers, polyester fibers, nylon fibers, vinylon fibers, and the like.

The invention also relates to a method for preparing a wound dressing, which comprises mixing a chitosan fiber, a chemically modified cellulose fiber and a calcium alginate fiber into a fabric by a nonwoven fabric process, preferably a needle punched nonwoven fabric process, and then fabricating the fabric Cut, pack and sterilize. The production process of the wound dressing of the present invention is preferably a needle-punched nonwoven process, and other non-woven processes such as a spunbond process can also be used.

Depending on the shape of the wound dressing required for different wounds, the fabric obtained by blending chitosan fibers, chemically modified cellulose fibers and calcium alginate fibers can be cut and/or cut into squares or rectangles to meet a variety of wound care applications. .

The wound dressing of the present invention can generally be packaged and sterilized by materials well known in the art. For sterilizing, gamma rays or epoxy oxime can be used.

The wound dressing of the present invention obtained according to the above description has both bacteriostatic, calcium ion supply and hygroscopicity. Example 1

A wound dressing containing 10% calcium alginate, 80% modified cellulose and 10% modified chitosan was prepared:

Raw material: Calcium alginate fiber, fineness 7.0dtex, length 45mm, absorption rate of A solution is above 1400%;

Modified cellulose with a fineness of 1.7 dtex and a length of 65 mm. The fiber is treated with carboxymethyl group, and its hygroscopic property contains 8.298 g of sodium chloride and 0.368 g of calcium chloride dihydrate per liter in the fiber state. The absorption rate of the solution (solution A) is above 1500%;

The modified chitosan has a fineness of 2.0 dtex and a length of 50 mm. The fiber is acylated, and its hygroscopic property contains 8.298 g of sodium chloride and 0.368 g of calcium chloride dihydrate per liter in the fiber state. The absorption rate of the solution (A solution) is above 200%;

Mix 7 grams of calcium alginate fiber, 56 grams of modified cellulose and 7 grams of modified chitosan and feed them into the carding machine with a loosening machine. The three fibers will be further used in the carding machine hopper. Mix. The web formed after carding is a homogeneous mixture of the three fibers. After that, the fiber web was laid and needled to form a needle-punched nonwoven fabric, and the weight was 135.3 g/m 2 .

The nonwoven fabric was cut into small pieces of 10 X 10 cm, and then packaged and sterilized with epoxy acetabulum to obtain a wound dressing.

According to YY/T 0471. 1-2004 "Test methods for contact wound dressings" § 1 and EN

13726-1 :2002/AC:2003 Test methods for primary wound dressings §3.2 Test absorption rate. The absorbance of the solution A of the dressing was 25.7 g / 100 cm 2 , and the salt uptake of the 0.9% NaCl solution was 26.0 g / 100 cm 2 . The universal wetness measured by the universal testing machine was CD 1.8 N/cm. Example 2

In order to observe the bacteriostatic performance of the dressing obtained in Example 1, Bacillus subtilis inoculated in an amount of about 250 μM ^ 10 Ε 6 cfu / mL was uniformly coated in a Petri dish, and then the dressing obtained in Example 1 was cut into 2 X 2 cm, respectively. Among them, the cells were continuously cultured at a constant temperature of 37 ° C and the growth of bacteria on each plate was observed.

Fig. 1 shows the inhibition zone of the dressing in the B. subtilis culture dish for 2 days, 3 days, and 8 days, and it can be seen that the bacteriostatic effect is maintained on the 8th day. Example 3

In order to observe the calcium release properties of the wound dressing obtained in Example 1, it was added to the test tube.

10 mL of 0.9% NaCl solution, and then the dressing obtained in Example 1 was cut into 2.5 X 2.5 cm, weighed and placed therein, and a simulation test of 1 day to 7 days was designed in parallel at 37 °C. The release properties are obtained from the calcium content of the dressing and the calcium content of the release liquid, as shown in Figure 2, the release capacity and time of calcium ions, wherein the total release ratio is the ratio of the total amount of calcium in the release liquid to the calcium content in the fiber. The total release ratio of calcium was 26.9%, and the average release rate was 21.7 ppm/0.1 g of fiber OmL of saline as measured by atomic absorption spectrophotometer. The content of calcium alginate as a calcium source in the blend is low, and the calcium release rate is also low. Example 4

Preparation of wound dressings containing 80% calcium alginate, 10% modified cellulose and 10% modified chitosan:

Ingredients: Calcium alginate fiber, fineness 7.0dtex, length 45 mm, absorption rate of solution A Above 1400%;

The modified chitosan has a fineness of 2.0 dtex and a length of 50 mm. The fiber is acylated, and its hygroscopic property contains 8.298 g of sodium chloride and 0.368 g of calcium chloride dihydrate per liter in the fiber state. The absorption rate of the solution (A solution) is above 200%.

56 g of calcium alginate fiber, 7 g of modified cellulose and 7 g of modified chitosan were mixed and opened by a loosening machine and fed to a carding machine, and the fibers were further mixed in a carding machine hopper. The web formed after carding is a homogeneous mixture of the three fibers. After that, the fiber web was laid and needled to form a needle-punched nonwoven fabric, and the weight was 129.1 g/m 2 .

According to YY/T 0471. 1-2004 "Test methods for contact wound dressings" § 1 and EN 13726-1 : 2002/AC: 2003 Test methods for primary wound dressings § 3.2 Test absorption rate. The absorbance of the solution A of the dressing was 25.7 g / 100 cm 2 , and the salt uptake of the 0.9% NaCl solution was 17.9 g / 100 cm 2 . The universal wetness measured by the universal testing machine was CD3.09 N/cm. Example 5

In order to observe the bacteriostatic performance of the wound dressing of Example 4, Bacillus subtilis inoculated in an amount of about 250 μM ^ 10 E6 cfu / mL was uniformly coated in a Petri dish, and then the dressing obtained in Example 1 was cut into 2 X 2 cm, respectively. It was placed therein, continuously cultured at a constant temperature of 37 ° C, and the growth of bacteria on each plate was observed.

Fig. 3 shows the inhibition zone of the dressing in the B. subtilis culture dish for 2 days, 3 days, and 8 days. No bacterial growth was observed from the dressing-like coverage area, and it was confirmed that the bacteriostatic effect was maintained on the 8th day. Example 6

In order to observe the calcium release properties of the wound dressing of Example 4,

10 mL 0.9% NaCl solution, then the dressing obtained in Example 4 was cut into 2.5 X 2.5 cm, weighed After that, it was placed therein, and a simulation test of 1 day to 7 days was designed in parallel at 37 °C. The release performance is obtained from the calcium content in the dressing and the calcium content in the release liquid. Figure 4 shows the release capacity and time change of calcium ions. The total release ratio is the ratio of the total amount of calcium in the release liquid to the calcium content in the fiber. The total release ratio of calcium was 20.6% on average with an atomic absorption spectrophotometer, and the average release rate was 118.4 ppm / 0.1 g fiber / 10 mL saline. The calcium alginate content as the calcium source in the blend is the highest, and the calcium release rate is also the highest. Example 7

Preparation of a wound dressing containing 33% calcium alginate, 33% modified cellulose and 33% modified chitosan:

23 g of calcium alginate fiber, 23 g of modified cellulose and 23 g of modified chitosan were mixed and opened by a loosening machine and fed to a carding machine, and the fibers were further mixed in the carding machine hopper. The web formed after carding is a homogeneous mixture of the three fibers. After that, the fiber web was laid and needled to form a needle-punched nonwoven fabric, and the weight was 132.6 g/m 2 .

13726-1 :2002/AC:2003 Test methods for primary wound dressings §3.2 Test absorption rate. The absorbance of the solution A of the dressing was 26.4 g / 100 cm 2 , and the salt uptake of the 0.9% NaCl solution was 26.7 g / 100 cm 2 . The universal wetness measured by the universal testing machine was CD 4.2 N/cm. Example 8

In order to observe the bacteriostatic performance of the wound dressing of Example 7, the inoculum amount was about 250 μΙ^ Χ 10E6 cfu/mL of Bacillus subtilis was uniformly coated in the culture dish, and then the dressing obtained in Example 7 was cut into 2 X 2 cm, and continuously cultured at a constant temperature of 37 ° C and the bacteria on each plate were observed. growing situation.

Fig. 5 shows the inhibition zone of the dressing in the B. subtilis culture dish for 2 days, 3 days, and 8 days, and it can be seen that the bacteriostatic effect was maintained on the 8th day. Example 9

To observe the calcium release properties of the wound dressing of Example 7, 10 mL of 0.9% NaCl solution was added to the test tube, and then the dressing obtained in Example 7 was cut into 2.5 X 2.5 cm, weighed and placed therein, at 37 ° C. Parallel design simulation tests from 1 day to 7 days. The release properties are obtained from the calcium content of the dressing and the calcium content of the release liquid. Figure 6 shows the release capacity and time of calcium ions. The total release ratio is the ratio of the total amount of calcium in the release liquid to the calcium content in the fiber. The total release ratio of calcium was 29.3%, and the average release rate was 82.9 ppm/0.1 g of fiber OmL of saline as measured by atomic absorption spectrophotometer. The content of calcium alginate as a calcium source in the blend is low, and the calcium release rate is also low.

Claims

Claim

A wound dressing having bacteriostatic, hygroscopic and calcium-promoting properties, characterized in that the wound dressing comprises chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers.

2. A wound dressing having bacteriostatic, hygroscopic and calcium-promoting properties, characterized in that the wound dressing is a mixture of chitosan fibers, calcium alginate fibers and chemically modified cellulose fibers.

The wound dressing according to any one of claims 1 to 2, wherein the wound dressing comprises from 5 to 90% by weight of chitosan fibers, from 5 to 90% by weight of calcium alginate fibers and from 5 to 90% by weight. % of the chemically modified cellulose fibers are blended, based on the total weight of the chitosan fibers, the chemically modified cellulose fibers, and the calcium alginate fibers.

The wound dressing according to any one of claims 1 to 3, wherein the ratio of the calcium alginate fiber to the chemically modified cellulose fiber is from 1:1 to 1:18.

The wound dressing according to any one of claims 1 to 3, wherein the ratio of the chitosan fiber to the chemically modified cellulose fiber is from 1:1 to 1:18.

The wound dressing according to any one of claims 1 to 3, wherein the ratio of the calcium alginate fiber to the chitosan fiber is from 1:1 to 1:18.

The wound dressing according to any one of claims 1 to 6, wherein the chitosan fiber, the chemically modified cellulose fiber and the calcium alginate fiber have a linear density of 0.5 to 5 dtex, preferably 2 to 4 dtex, respectively.

The wound dressing according to any one of claims 1 to 6, wherein the chitosan fiber, the chemically modified cellulose fiber and the calcium alginate fiber have a length of 10 mm to 125 mm, preferably 25 to 85 mm, respectively.

9. The wound dressing according to any one of claims 1 to 6, wherein the chitosan fiber is The modified cellulose fiber and the calcium alginate fiber respectively contain a surfactant.

The wound dressing according to any one of claims 1 to 6, wherein one or both of the chitosan fiber, the calcium alginate fiber and the chemically modified cellulose fiber contain a bacteriostatic agent.

A method of preparing a wound dressing according to any one of claims 1 to 9, wherein the chitosan fiber, the chemically modified cellulose fiber and the seaweed are passed through a nonwoven fabric process, preferably a needle punched nonwoven process The calcium acid fiber is blended to obtain a fabric which is then cut, packaged and sterilized.

12. A wound dressing having bacteriostatic, hygroscopic and calcium-promoting properties, characterized in that the wound dressing comprises any two of a chitosan fiber, a calcium alginate fiber and a chemically modified cellulose fiber and a non-sol. Fiber.