CN101590287B

CN101590287B - Wound filling

Info

Publication number: CN101590287B
Application number: CN200810109330A
Authority: CN
Inventors: 贾晓蕾; 邱凯; 王岩; 李宇
Original assignee: 3M Innovative Properties Co
Current assignee: 3M Innovative Properties Co
Priority date: 2008-05-28
Filing date: 2008-05-28
Publication date: 2012-10-03
Anticipated expiration: 2028-05-28
Also published as: CN101590287A

Abstract

The invention provides a wound filling which contains eugenol which accounts for 0.1-20 percent of the total weight of the wound filling, aquagel raw material which accounts for 1-15 percent of the total weight of the wound filling, and the balanced of water.

Description

Wound filling

Technical field

The present invention relates to a kind of Wound filling.

Background technology

Wound filling is applicable to the nursing of open wound; Generally be used for skin corium ulcer, gangrene is utilized the principle of moist wound healing; Make wound after hemostasis, removing slough; Be stored in the moistening environment, in the state of not forming a scab, promote the formation and the growth of granulation tissue, finally make wound recover normal.But moistening environment itself also helps multiplying of antibacterial and breeds, and therefore expects that highly Wound filling possesses good antibacterial performance.In addition, because Wound filling directly acts on wound, it is very high to human safety with to the skin low irritant therefore also to require it to have.

Summary of the invention

The invention provides a kind of Wound filling, account for the eugenol of the 0.1-20% of Wound filling gross weight, account for 1～15% the hydrogel raw material of Wound filling gross weight and the water of surplus.

Above-mentioned summary description of the present invention is not in order to describe each disclosed embodiment of the present invention or each concrete instance.Following detailed has more specifically been enumerated illustrative embodiment.

Description of drawings

Fig. 1 a-1d has provided the result according to the inhibition zone test of the Wound filling that comprises eugenol of certain embodiments of the present invention,

Fig. 1 e has provided the result of inhibition zone test who does not comprise eugenol but comprise the Wound filling of chitosan.

The specific embodiment

Unless otherwise indicated, term " Wound filling " is meant the amorphous aquagel compositions that is used to provide moist wound healing environment.Know that moist wound healing environment can promote wound healing.

Unless otherwise indicated, term " hydrogel raw material " is meant and can be dispersed in the material that forms hydrogel in the water.It includes but not limited to, for example, and polymer, gel and resin.

Unless otherwise indicated, term " eugenol " is meant that wherein the content of 4-pi-allyl-2-methoxyphenol is the material of 98-100wt%, and it is derived from extracted form natural plant or chemosynthesis.

Unless otherwise indicated, all numerical value all are interpreted as titled with term " about ", and the numerical range that two-end-point limits comprises that the institute in this scope have a few, and (for example scope 0.1-20 comprises 0.1,0.15 to the interior have a few of this scope just as all having spelt out that kind; 0.2,0.25,0.3,0.35,0.4; 0.425,1,2,5; 10,15,18 and 20).Unless otherwise indicated, all percents among the present invention, umber, ratio all is to be the basis with weight.

According to certain embodiments of the invention, Wound filling also contains other additive.Other additive for example can be citric acid; Malic acid, tartaric acid, oxalic acid, succinic acid, lactic acid and acetic acid, organic acid or mineral acids such as phosphoric acid, solutions of weak acidity can make Wound filling possess certain viscosity; Be more suitable for being used for wounds such as corium ulcer, the broadspectrum antibiotic wet environment is provided.

According to certain embodiments of the invention, eugenol is for separating the extract of purifying and forming from Oleum Caryophylli or other aromatic oil that contains eugenol, and wherein the content of 4-pi-allyl-2-methoxyphenol is not less than 98%.

The eugenol that in certain embodiments of the invention, adopts is generally colourless or little yellowy clear liquor, and the relative density in the time of 25 ℃ is 1.060～1.068, and boiling range is 252～255 ℃, and index of refraction is 1.538～1.542.

Eugenol is the main component of Flos Caryophylli Flos caryophy lli and Oleum Ocimi Gratissimi (Oleum ocimi gratissimi), and multiple pharmacologically actives such as broad-spectrum antibacterial, anesthesia, analgesic, antioxidation, antitumor, promotion Transdermal absorption, the mosquito of dispelling are arranged.Eugenol can suppress or kill staphylococcus aureus Staphylococcus aureu, staphylococcus epidermidis Staphylococcus epidermidis, bacillus subtilis Bacillus subtilis, shigella flexneri Shigella dysenteriae, salmonella paratyphi Bacillus paratyphi, escherichia coli Escherichia coli, mycete Aspergillus, Malassezia furfur Malassezia furfur, Pi Fu Xian bacterium Ristella lichenis-plani, fungus fungus, yeast Zymophilus etc. to some extent; Therefore eugenol can be through suppressing staphylococcus aureus; Main Clinical microorganism such as bacillus pyocyaneus, escherichia coli, Candida albicans reduces infection, continues antibiotic.

Eugenol can directly be purchased, and for example, trade Co., Ltd buys from the upper Changjiang region, Shanghai, also can be through traditional eugenol extraction process preparation.Traditional eugenol extraction process mainly contains two kinds of steam distillation and ethanol refluxing processes.Come two kinds of methods are elaborated respectively through concrete example below.

1. steam distillation

Get the 20g Flos Caryophylli in flask, the adding distil water soaked overnight is used water vapour distillation, and till the about 200mL of distillate, altogether 3.5h consuming time places the cooling back and saltouts with NaCl, tells grease, and reuse anhydrous Na 2SO4 is dry, weigh, calculate productive rate.Purity is more than 92%.

2. ethanol refluxing process

In the 250mL round-bottomed flask, add the ethanol of 20g Flos Caryophylli and 200mL 95%, little refluxed 60min that boils filters.Filtrating is fixed (pH=9～10) with 5% NaOH 30ml, filters, and steams and removes ethanol, uses the 30mL extracted with diethyl ether 3 times at every turn; Water layer is used the 6mol/L hcl acidifying, transfers pH value of solution=5, uses the 30mL extracted with diethyl ether 3 times at every turn, and combining extraction liquid is dry with anhydrous Na 2SO4, steams and removes ether, gets product, weighs, calculates productive rate.Purity is more than 95%.

In the cymogene Oleum sesami according to above-described method extraction, except that the main component eugenol, also often contain β-caryophyllene, acetyl group eugenol and α-caryophyllene, can further separate as required purifies obtains the eugenol of content more than 99%.

In some embodiments; Hydrogel raw material in the Wound filling comprises more than one water soluble polymers; For example water-soluble cellulose and derivant thereof, polyvinylpyrrolidone, polyacrylate and derivant thereof; One or more combination wherein such as polyacrylamide and derivant thereof, carbomer, guar gum, gelatin, calcium alginate/sodium fiber, polysaccharide etc.

Wound filling of the present invention; For example; Can prepare through the eugenol that in base material (for example hydrogel raw material obtain after with the deionized water swelling hydrogel), adds requirement, also can through join hydrogel raw material and eugenol in the deionized water and fully mixing prepare.

Wound filling of the present invention, production technology is simple, and broad-spectrum antiseptic is low to skin irritation, can promote wound healing safely and effectively.

Embodiment:

Raw material:

Guar gum, Shanghai GaoWei Chemical Co., Ltd;

Eugenol, the upper Changjiang region, Shanghai trade Co., Ltd, purity >=98%;

Strain: represent gram-positive bacteria with staphylococcus aureus Staphylococcus aureu ATCC6538; Represent gram-negative bacteria with escherichia coli Escherichia coli ATCC8099 and bacillus pyocyaneus Pseudomonasaeruginosa ATCC9027; Candida albicans Candida albicansATCC10231 represents fungus.Above strain is all purchased the institute of microbiology in Shanghai City; Culture medium: bacteria culture media is that pH value is 7.2 Nutrient agar, and fungi culture medium is that pH value is 6.8 diiodocosin (rose-red) culture medium.Above culture medium is all purchased disease control and prevention center in Shanghai City.

Embodiment 1: the preparation of Wound filling

Guar gum (Shanghai GaoWei Chemical Co., Ltd) 3 grams and eugenol (upper Changjiang region, Shanghai trade Co., Ltd) 0.5 gram are joined in the 96.5 gram deionized waters; Under the room temperature vigorous stirring, in system, drip the 20wt% citric acid solution; Make system pH=5.0～5.5, guarantee fully swelling of guar gum.Stir the hydrogel that obtains having certain viscosity after ten minutes.

The mensuration of eugenol inhibition zone

With reference to the disinfection technology standard 2.1.8.2 of Ministry of Health of the People's Republic of China; Pass judgment on the antibacterial activity of eugenol with the mensuration of inhibition zone: staphylococcus aureus Staphylococcus aureuATCC6538 to following strain; Escherichia coli Escherichia coli ATCC8099; Bacillus pyocyaneus Pseudomonasaeruginosa ATCC9027 (with Nutrient agar as culture medium), Candida albicans Candidaalbicans ATCC10231 (adopting rose-bengal (rose-red) culture medium).

Concrete detection method: test specimen (the corresponding a kind of strain of each sample) does not pass through sterilization treatment.Bacteria suspension (10 with 3 milliliters of dilutions ⁶～10 ⁷Cfu/ml) join in 300 milliliters of the liquid culture medium under 47 ℃ of water bath condition, and mix homogeneously.Make in the petri diss it solidify that (clump count in agar is greatly about 10 about 20 milliliters of above-mentioned media transfer that are mixed with bacteria suspension ⁴～10 ⁵Cfu/ml, the clump count in rose-bengal (rose-red) culture medium is greatly about 10 ⁴～10 ⁵Cfu/ml).The filter paper (10 mm dia) that will be soaked with eugenol then as early as possible is put in the culture medium, cultivates 24 hours at 37 ℃.Each sample is done three parallel appearance.As contrast, also done this inhibition zone test with chitosan.

Table one: antibacterial circle diameter

Annotate: X representes not have inhibition zone

Measure eugenol minimal inhibitory concentration (being called for short MIC among this paper)

According to the disinfection technology standard 2.1.8.4 of Ministry of Health of the People's Republic of China, measure the MIC of eugenol to various bacterium colonies, the result is following:

Table two: eugenol MIC

Strain MIC (%)

Escherichia coli 0.1

Staphylococcus aureus 0.05

Can find out from last table, eugenol to the MIC of gram-negative bacteria and positive bacteria all well below the safe concentration of eugenol to skin.

The challenge test of Wound filling

According to GB15979-2002, Wound filling is carried out challenge test in 28 days, result such as following table:

Table three: Wound filling challenge result of the test

Explain:

1. mixed vaccine is escherichia coli+bacillus pyocyaneus+staphylococcus aureus;

2. initial clump count: escherichia coli: 6.1*10 ⁶Cfu/g, bacillus pyocyaneus: 3.45*10 ⁶Cfu/g, staphylococcus aureus: 2.0*10 ⁶Cfu/g, Candida albicans: 5.0*10 ⁶Cfu/g, mixture: 6.55*10 ⁶Cfu/g

3.++ the expression line has the objective microbe growth;-expression line driftlessness growth of microorganism

Embodiment 2

Guar gum 1 gram and eugenol 2 grams are joined in the 94.5 gram deionized waters, under the room temperature vigorous stirring, in system, drip 2.5 grams, 20% citric acid solution, the assurance guar gum is swelling and form gel fully.Stir the hydrogel wound filler 1# that obtains having certain viscosity after ten minutes.

Embodiment 3

Guar gum 2 gram and eugenol 0.1 gram are joined in the 97.8 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.1 gram, 20% citric acid solution, the assurance guar gum is swelling and form gel fully.Stir the hydrogel wound filler 2# that obtains having certain viscosity after ten minutes.

Embodiment 4

Guar gum 15 gram and eugenol 20 grams are joined in the 65 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.05 gram, 20% citric acid solution, the assurance guar gum is swelling and form gel fully.Stir the hydrogel wound filler 3# that obtains having certain viscosity after ten minutes.

Embodiment 5

Guar gum 8 gram and eugenol 10 grams are joined in the 82 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.07 gram, 20% citric acid solution, the assurance guar gum is swelling and form gel fully.Stir the hydrogel wound filler 4# that obtains having certain viscosity after ten minutes.

Embodiment 6

Hydroxyethyl-cellulose 5 gram and eugenol 5 grams are joined in the 90 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.05 gram, 20% citric acid solution, the assurance hydroxy ethyl fiber is swelling and form gel fully.Stir the hydrogel wound filler 5# that obtains having certain viscosity after ten minutes.

Embodiment 7

Carboxymethyl cellulose 5 gram and eugenol 2 grams are joined in the 93 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.05 gram, 20% malic acid solution, the assurance carboxymethyl cellulose is swelling and form gel fully.Stir the hydrogel wound filler 6# that obtains having certain viscosity after ten minutes.

Embodiment 8

Polyvinyl alcohol 5 gram and eugenol 5 grams are joined in the 89.9 gram deionized waters, under the room temperature vigorous stirring, in system, drip 0.1 gram, 20% malic acid solution, the assurance polyvinyl alcohol is swelling and form gel fully.Stir the hydrogel wound filler 7# that obtains having certain viscosity after ten minutes.

Table four: the Wound filling challenge result of the test of embodiment 2-8

Embodiment

Wound filling

Hydrogel content (wt%), kind

Eugenol wt%

Mixed vaccine challenge test line result

Fungus challenge test line result

2	1#	1 guar gum	2	The driftlessness growth of microorganism	The driftlessness growth of microorganism
						3	2#	2 guar gums	0.1	The driftlessness growth of microorganism	The driftlessness growth of microorganism
4	3#	15 guar gums	20	The driftlessness growth of microorganism	The driftlessness growth of microorganism
						5	4#	8 guar gums	10	The driftlessness growth of microorganism	The driftlessness growth of microorganism
6	5#	5 hydroxyethyl-celluloses	5	The driftlessness growth of microorganism	The driftlessness growth of microorganism
						7	6#	5 carboxymethyl celluloses	2	The driftlessness growth of microorganism	The driftlessness growth of microorganism
8	7#	5 polyvinyl alcohol	5	The driftlessness growth of microorganism	The driftlessness growth of microorganism

Explain:

1. mixed vaccine is escherichia coli+bacillus pyocyaneus+staphylococcus aureus; Initial bacterium colony adds up to 2.35*10 ⁷Cfu/g

2. the initial bacterium colony of fungus adds up to 5.6*10 ⁶Cfu/g

3. test temperature: antibacterial is 36 ± 1 ℃; Mycete, yeast are 28 ± 1 ℃; Test period: 28 days.

Claims

1. Wound filling; It comprises: the eugenol that accounts for the 0.1-20% of Wound filling gross weight; Account for 1～15% hydrogel raw material of Wound filling gross weight; The acid that is selected from citric acid, malic acid, tartaric acid, oxalic acid, succinic acid, lactic acid, acetic acid, phosphoric acid of 0.01-0.5wt%, and the water of surplus

Wherein said eugenol is that the content of wherein 4-pi-allyl-2-methoxyphenol is the material of 98-100wt%, and

Said hydrogel raw material is water-soluble cellulose and derivant thereof; Polyvinylpyrrolidone; Polyacrylate and derivant thereof, polyacrylamide and derivant thereof, carbomer, guar gum, gelatin, calcium alginate/sodium fiber, the combination of one or more in the polysaccharide.

2. the Wound filling of claim 1, the wherein extract of eugenol for obtaining from the aromatic oil that contains eugenol.