CN1136012C - Wound dressing and its prepn. - Google Patents

Wound dressing and its prepn. Download PDF

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Publication number
CN1136012C
CN1136012C CNB001212192A CN00121219A CN1136012C CN 1136012 C CN1136012 C CN 1136012C CN B001212192 A CNB001212192 A CN B001212192A CN 00121219 A CN00121219 A CN 00121219A CN 1136012 C CN1136012 C CN 1136012C
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China
Prior art keywords
dressing
collagen protein
hyaluronic acid
wound
collagen
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Expired - Fee Related
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CNB001212192A
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Chinese (zh)
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CN1337270A (en
Inventor
黄玲惠
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SHIN ERA TECHNOLOGY Co Ltd
WUN TAIX CHEMISTRY CO Ltd
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SHIN ERA TECHNOLOGY Co Ltd
WUN TAIX CHEMISTRY CO Ltd
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Priority to CNB001212192A priority Critical patent/CN1136012C/en
Publication of CN1337270A publication Critical patent/CN1337270A/en
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Publication of CN1136012C publication Critical patent/CN1136012C/en
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Abstract

The present invention relates to a wound dressing which comprises collagen or derivative thereof and hyaluronic acid or derivative thereof. The present invention also provides a method for preparing the wound dressing.

Description

Wound dressing and preparation method thereof
Technical field
The present invention relates to a kind of wound dressing, this wound dressing comprises collagen protein and hyaluronic acid.The present invention also provides a kind of method for preparing this wound dressing.
Background technology
Wound dressing is a kind of material that is placed on wound of applying, and can protect wound rapidly in order to avoid the infection of pathogen and run off excessive body fluid and blood when wound just forms.Present commercially available wound dressing, how only tool is protected and germ-resistant effect, and the effect that promotes wound healing can't be provided.Because it can't promote wound healing, make the wound of healing stay tangible cicatrix mostly.
Impel the method for wound healing, be disclosed in many prior aries.For example, United States Patent (USP) the 5th, 489,304 and 5,716, No. 411 the skin regeneration method of a kind of wound or burn and scald is disclosed, this method is that the substrate of making after earlier collagen protein-glycosaminoglycans being mixed is covered in wound surface, make this substrate infiltrate via the blood vessel of health tissues and mesenchymal cell, repaste covers one deck through cultured animals or human cuticular cellulose, to impel skin regeneration.United States Patent (USP) the 4th, 614 discloses for No. 794 and a kind of vegetalitas polysaccharide (as alginic acid) and biological decomposable protein (as collagen protein) have been formed the method for porous protein/polysaccharides compound, and this complex can be used as wound dressing.United States Patent (USP) the 5th, 698 discloses a kind of Graftskin that is used to cover wound No. 228, and it is the chitin of sepiellae seu sepiae and the lamination thing of collagen protein of fish skin.In addition, United States Patent (USP) the 5th, 977, a kind of medicament and hyaluronic medical composition that contains treatment or alleviate dermatosis disclosed for No. 088, this medical composition is to utilize the hyaluronic acid promotion or cause in the ill skin of being delivered to of medicament that it also can be accumulated medicament and prolong the time that medicament rests on this position.
The time that method that cicatrizes a wound in the above-mentioned prior art or dressing can't cicatrize a wound can more effectively shorten, and when being used for large tracts of land and darker wound, can't avoid staying cicatrix.
Summary of the invention
The invention provides the wound dressing of the above-mentioned shortcoming of a kind of not tool.
The present invention mainly provides a kind of wound dressing, and this wound dressing comprises collagen protein and hyaluronic acid.
The present invention also provides a kind of method for preparing wound dressing.
Description of drawings
Fig. 1 is the wound tissue's slice map after wound dressing of the present invention is applied to wound.
Fig. 2 is according to the prepared wound dressing of the method for example 1.
Fig. 3 is the flow chart of the preparation method of example 2.
Fig. 4 is the flow chart of the preparation method of example 3.
Fig. 5 is according to the prepared wound dressing finished product of the method for example 2 photographic view.
The simple declaration of main element in the accompanying drawing:
10 expression polyamine ester film base materials;
The Polyurethane patch of 11 expression autohension;
The base material of amido or carboxyl is rich in 12 expressions;
13 expressions are through the activatory activation base material of epoxide;
20 expressions contain hyaluronic collagen protein sheet;
The aseptic collagen solution of 21 expressions;
The spongy collagen protein of 22 expressions;
23 expression collagen protein;
30 expression container models; And
40 expression hyaluronic acids.
Detailed Description Of The Invention
The present invention mainly provides a kind of wound dressing, it comprises collagen, and hyaluronic acid, the respond well dressing that cicatrizes a wound can be provided, it also can be widely used in general wound and reach more greatly or darker wound, can obviously shorten the time of wound healing, and the outward appearance of cambium after the healing and surrounding tissue is approached, can avoid staying obvious scar.
One of wound dressing of the present invention forms and is divided into collagen, is the chief component protein of skin. Be applicable to collagen of the present invention, include but not limited to: the mixture of the first collagen type, the first type or the 3rd collagen type or the mixture of other different shaped collagens. Can be made into any pattern well-known to those having ordinary skill in the art and use, for example spongy, film-form or colloidal. According to the embodiment of the invention, the processing such as collagen can freeze-drying, natural seasoning, boulton process obtains required pattern.
Another composition of wound dressing of the present invention is divided into hyaluronic acid. Hyaluronic acid is the polysaccharide of high viscosity, and tool repeats the glucuronic acid of disaccharide and the polymerizable molecular of N-acetyl glucosamine, and molecular weight is between 4,000 to 8 * 106
Wound dressing of the present invention can further comprise and includes but not limited to polysaccharide: the derivant of chondroitin sulfate, alginate, chitin, chitosan and these polysaccharide.
Dressing of the present invention also can further comprise other medicament, includes but not limited to: antiphlogistic medicament, somatomedin, antibiotic or infection medicament, or other can promote the factor of wound healing.
Wound dressing of the present invention can be further in the mode of surface coated or adhesion, or any mode well-known to those having ordinary skill in the art is coated on a substrate surface, uses with convenient, and reaches and isolate the effect that infects.According to the present invention, coating method includes but not limited to: (1) surface coated, and can brushing, impregnation or the mode of directly dripping be applied to substrate surface with materials such as collagen protein; (2) adhesion can be adhered together material such as collagen protein and this substrate surface with sticker.
Be common to base material of the present invention and can be any base material well-known to those having ordinary skill in the art, for example the polyamine ester film of gauze, the Polymer Synthesizing base material of tool biocompatible, high oxygen flow or pellosil etc.This base material can be attached with stickum, so that dressing of the present invention is fixed in skin surface, for example dressing of the present invention is attached to an O.K. and tacks down.
Collagen protein, hyaluronic acid or polysaccharide that dressing of the present invention is included, can any mode well-known to those having ordinary skill in the art handle, for example can be made into blend, mixture or copolymer or handle, or give combination through after the chemical modification in the mode of impregnation.
The dressing made according to the present invention has biocompatible, is easily decomposed by organism and absorbs, and can promote wound healing, shortens the time of wound healing, can make wound tissue not stay tangible cicatrix near the tissue of its periphery.
The present invention also provides a kind of method for preparing wound dressing, comprises that mixing collagen protein and hyaluronic acid are to make dressing.According to a specific embodiment of the present invention, this prepares the method for wound dressing, can earlier the collagen protein lyophilization be made a collagen protein sheet, hyaluronic acid is coated this collagen protein sheet again, and dressing is made in lyophilization once again.Another specific embodiment of the present invention comprises earlier makes a collagen protein sheet with the collagen protein lyophilization, again this collagen protein sheet is dipped in hyaluronic acid solution after, dressing is made in lyophilization once again.
Embodiment
Following embodiment is used for the present invention is further illustrated, and is not that improvement and application that the training centre of any those skilled in the art description according to the present invention is reached all belong to category of the present invention in order to restriction the present invention.
Embodiment 1
Drip on the surface of polyamine ester film base material 10 or the collagen liquid of coating concentration 3 mg/ml, lyophilization is to form the wound dressing of tool collagen protein, be coated with the hyalomitome acid solution of last 0.1 to 10 mg/ml subsequently again, lyophilization once again is rich in hyaluronic collagen protein wound dressing with formation.Sterilize with 0.4 to 4.0M radiating γ-lonizing radiation again after the packing.This finished product can be used as home-use wound dressing or surgery and applies cover material as shown in Figure 2.
Embodiment 2
The flow process of this method as shown in Figure 3.The aseptic collagen solution 21 of 3 mg/ml is placed container model 30, adjust its pH value to neutral.In 37 ℃ of following gels after 0.2 to 24 hour, lyophilization is carried out in taking-up, make it become spongy collagen xxii protein, after the hyalomitome acid solution of an impregnation or last 0.1 to 10 mg/ml, lyophilization once again, and with the Polyurethane patch 11 of tool autohension bonding after, promptly become wound dressing, its finished product as shown in Figure 5.
Embodiment 3
Di-epoxide and the base material 12 that is rich in amido are reacted down in room temperature, or react down to make activation base material 13 with in 90 to 130 ℃ of the base materials that is rich in carboxyl.Then with the unreacted epoxide of deionized water wash, react 4 to 120 hours at normal temperatures with the solution of the collagen protein 23 of concentration 1 to 10 mg/ml then after, carry out lyophilization, obtain the collagen protein base material of covalency bond, this is finished product A.Can be the hyaluronic acid 40 of 0.01 to 20 mg/ml also, carry out lyophilization again, obtain product B a finished product A impregnation or a last concentration.The method and product are as shown in Figure 4.
Embodiment 4
Finished product A institute's impregnation among the embodiment 3 or the hyaluronic acid that drips also can its objective is to be to improve time and the effect that hyaluronic acid is stranded in wound earlier through chemical modification or activation.Hyaluronic chemical modification or activation can following three kinds of methods be carried out:
Method one: the hyaluronic preparation of aldehyde radicalization
Hyaluronic acid is dissolved in Na 2B 4O 7In, add NaBH 4Carry out ring-opening reaction, carry out lyophilization again.To be dissolved in the imidazoles through cryodesiccated product, add sodium periodate (NaIO again 4) reaction, promptly obtain the aldehyde radical hyaluronic acid.
Method two: aminated hyaluronic preparation
Hyaluronic acid is placed under 10 to 40 ℃ of 10 to 4000 millitorr vacuums and the room temperature, feed N 2Or NH 3And impose the microwave plasma of 20 to 1000 watts of electric power, can be aminated hyaluronic acid with the hyaluronic acid upgrading.
Method three: the activatory hyaluronic preparation of cyanogen bromic acid (CNBr)
The pH value of hyalomitome acid solution is adjusted into 14, adds cyanogen bromic acid solution again, and reacted 2 to 60 minutes, promptly obtain the activatory hyaluronic acid of cyanogen bromic acid, unreacted cyanogen bromic acid can dialysis be removed.
Embodiment 5
As the dressing methods of example 1,2 and 3 preparations, wherein the hyalomitome acid solution is used hyaluronic acid, the alginic acid of same-size ratio, the mixed liquor of water solublity fourth polysaccharid derivative instead.
Embodiment 6
Set up the full deep wounds of 2 square centimeters of surface areas in the guinea pig back, put the dressing of collagen protein dressing, collagen protein and cross-linking hyaluronic acid respectively, or the deposited material that covers of the Tegaderm that does not contain any material, observe the time of superficial cut healing, and do the pathology section examination of callus in different time points sampling, with the interpretation wound healing time.
Test general dressing and the dressing of the present invention time for wound healing according to above-mentioned method of testing, its result is as shown in table 1:
Table 1
The wound healing observational technique Do not contain dressing Collagen protein dressing Collagen protein and cross-linking hyaluronic acid dressing
Surface observation 12~14 days 9~13 days 8~12 days
The pathological section interpretation 20~40 12~18 10~15 days
Clear as can be known by table 1, the general dressing of wound dressing of the present invention has short wound healing time really.And as shown in Figure 1, after wound dressing of the present invention was used for wound, the structure of callus was bordering on normal organizational structure, was much better than the use result of other wound dressings, and the latter has organizational structure more closely.

Claims (16)

1. wound dressing, it comprises collagen protein and hyaluronic acid, this dressing is coated on the substrate surface in the mode of coating or adhesion.
2. dressing as claimed in claim 1, wherein this dressing further comprises polysaccharide.
3. dressing as claimed in claim 2, wherein said polysaccharide are chondroitin sulfate, alginate, chitin or chitosan.
4. dressing as claimed in claim 1, wherein said collagen protein are to be the mixture of first collagen type, first type or the 3rd collagen type or the mixture of other different shaped collagen protein.
5. that dressing as claimed in claim 1, wherein said collagen protein are is spongy, film like or colloidal.
6. as claim 1 or 5 described dressing, wherein said collagen protein is handled through lyophilization.
7. dressing as claimed in claim 1, wherein said hyaluronic acid is through aldehyde radicalization, aminated or cyanogen bromic acid activation.
8. as claim 1,2 or 3 described dressing, it further comprises antiphlogistic medicament, somatomedin, antibiotic or infection medicament.
9. method for preparing wound dressing, it comprises and mixes collagen protein and hyaluronic acid making dressing, with the coating or the mode of adhering described dressing is coated on a substrate surface.
10. method for preparing wound dressing, it comprises makes a collagen protein sheet with the collagen protein lyophilization earlier, hyaluronic acid is coated described collagen protein sheet again, and described dressing is made in lyophilization once again.
11. a method for preparing wound dressing, it comprises earlier makes a collagen protein sheet with the collagen protein lyophilization, more described collagen protein sheet is dipped in hyaluronic acid solution after, described dressing is made in lyophilization once again.
12. as claim 9,10 or 11 described methods, it further comprises and is mixed into a polysaccharide and makes dressing.
13. as claim 10 or 11 described methods, that wherein said collagen protein is made into is spongy, film like or colloidal.
14. method as claimed in claim 12, wherein said polysaccharide are chondroitin sulfate, alginate, chitin or chitosan.
15. as claim 9,10 or 11 described methods, it comprises earlier hyaluronic acid through aldehyde radicalization, aminated or cyanogen bromic acid activation.
16. as claim 9,10 or 11 described methods, it comprises that further interpolation antiphlogistic medicament, somatomedin, antibiotic or infection medicament are to dressing.
CNB001212192A 2000-08-07 2000-08-07 Wound dressing and its prepn. Expired - Fee Related CN1136012C (en)

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Application Number Priority Date Filing Date Title
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CN1136012C true CN1136012C (en) 2004-01-28

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007033591A1 (en) * 2005-09-22 2007-03-29 Shanshan Xi Active prosthetic material for wounds
CN101001649B (en) * 2004-07-09 2011-08-31 弗罗桑医疗设备公司 Hemostatic compositions comprising hyaluronic acid and methods of making the same

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CZ12015U1 (en) * 2002-01-18 2002-02-25 Cpn Spol. S R.O. Preparation for preventing adhesion of a bandage to a wound
CN1319604C (en) * 2004-09-13 2007-06-06 中国医学科学院生物医学工程研究所 Double layer composite collagen base guide tissue regeneration film and its preparing method
US7993678B2 (en) * 2005-09-26 2011-08-09 Novozymes Biopolymer A/S Hyaluronic acid derivatives
CN102120033A (en) * 2011-03-07 2011-07-13 温州医学院 Collagen sustained-release carrier material for promoting repair of various traumas in oral and maxillofacial regions and method for preparing same
CN102671231B (en) * 2011-12-20 2013-12-25 浙江省海洋开发研究院 Method for preparing marine-derived compound collagen dressing
CN102580139A (en) * 2012-03-27 2012-07-18 黑龙江省华信药业有限公司 Collagen hyaluronic acid dressing
TWI607760B (en) * 2014-07-29 2017-12-11 國立成功大學 Cell tissue gel containing collagen and hyaluronan
CN104491915B (en) * 2015-01-06 2017-04-05 穆向明 One kind is postoperative to prevent being adhered medical dressing and preparation method thereof
KR101841469B1 (en) * 2015-01-30 2018-03-23 (주)메디팁 Method for manufacturing wound covering material using biopolymer and wound covering material using biopolymer manufactured by the same
CN105056279A (en) * 2015-08-12 2015-11-18 杭州承前生物科技有限公司 Double-layer polyurethane-based collagen-compounded dressing
CN105797203A (en) * 2016-04-01 2016-07-27 厦门迅朗生物技术有限公司 Alginate fiber based collagen sponge dressing and preparation method thereof
CN106727246A (en) * 2017-02-08 2017-05-31 上海元茵生物科技有限公司 Calf serum cell nutrient solution
CN108619552B (en) * 2017-03-23 2021-06-08 苏州明镜医疗科技有限公司 Absorbable wound repair material for adsorbing GGTAl gene knockout pig collagen and preparation method thereof
CN111760066B (en) * 2020-06-09 2022-03-04 北京化工大学 Hemostatic gel and preparation method and application thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101001649B (en) * 2004-07-09 2011-08-31 弗罗桑医疗设备公司 Hemostatic compositions comprising hyaluronic acid and methods of making the same
WO2007033591A1 (en) * 2005-09-22 2007-03-29 Shanshan Xi Active prosthetic material for wounds

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