Summary of the invention
In order to solve the problems of the technologies described above, the invention provides a kind of colloidal solution for wound reparation and preparation method thereof, this colloidal solution has excellent stability under various environmental conditions, particularly under its wound pH value in agglutination or after being infected (6.5-8.5) used, thus applied range, good anti-bacterial effect, the wound repair that can promote, safe and reliable, easy to use.。
The invention provides a kind of colloidal solution repaired for wound, it is containing, for example the component of lower percentage by weight: polysaccharide sodium 0.5-5%, cyclodextrin 0.1-0.5%, promoter 0. 1-0.5% gather in the amino Portugal of carboxylic, all the other are normal saline, based on the gross weight of described colloidal solution.
The present invention also provides a kind of preparation method of the above-mentioned colloidal solution for wound reparation, and it is characterized in that, above-mentioned each component obtains colloidal solution by grinding step and ultrasonic disperse operation.
In the colloidal solution repaired for wound of the present invention, the aminopolysaccharide containing carboxylic amino that polysaccharide sodium is degree of polymerization 50-500 gathers in the amino Portugal of described carboxylic.The amino Portugal of carboxylic gathers polysaccharide sodium and contains positively charged amino, all has obvious clinical promoting healing, hemostasis, antibacterial, the effect that controls to ooze out, reduce cicatrization to multiple wound.
In the colloidal solution repaired for wound of the present invention, described cyclodextrin is the cyclic oligosaccharide containing 6-12 D-glucopyranose units.
In the colloidal solution repaired for wound of the present invention, described promoter is selected from the one in glycerol, xylitol, Sorbitol, propylene glycol, dexpanthenol.Selected by the present invention, promoter is polyhydric alcohol, has water solublity, emulsibility, the performance that film property, moisture retention etc. are excellent.
The preparation method of a kind of colloidal solution for wound reparation of the present invention, comprises the steps:
1) take the amino Portugal of carboxylic and gather polysaccharide sodium, cyclodextrin and promoter, and mix homogeneously, subsequently under 60 DEG C of-80 DEG C of conditions, obtained the cyclodextrin clathrate gathering polysaccharide sodium in the amino Portugal of carboxylic by grinding step,
2) cyclodextrin clathrate that polysaccharide sodium gathers in amino for carboxylic Portugal is dissolved in normal saline by ultrasonic disperse operation, filters and remove insoluble matter, high-temperature vapour sterilizing subsequently, the obtained described colloidal solution repaired for wound.
For above-mentioned steps 1), it is characterized in that, described grinding step is that each component grinds 60-300 minute in Achates tank.
For above-mentioned steps 2), it is characterized in that, the temperature of described ultrasonic disperse operation is 20 DEG C-50 DEG C, and the temperature range of described high-temp steam sterilizing is 120 DEG C-160 DEG C.
A kind of colloidal solution for wound reparation is used for the reparation of human body skin and wound surface by the present invention, has protection mesothelial tissue t-PA active, reduces tissue fluid and ooze out, and protection, isolation, lubrication wound wound surface, promote the effect of wound wound healing.
Colloidal solution for wound reparation of the present invention gathers polysaccharide sodium for main function raw material with the amino Portugal of carboxylic, in wound surface film forming, can promote wound healing.The present invention gathers polysaccharide sodium with cyclodextrin and the amino Portugal of carboxylic and forms clathrate, and this clathrate height is water-soluble, has very high biocompatibility.
Surprisingly, adopt the amino Portugal of cyclodextrin and carboxylic to gather polysaccharide sodium in the present invention and forms the stability that clathrate can improve the described colloidal solution repaired for wound greatly, the stability particularly under wound pH value in agglutination or after being infected (6.5-8.5) of its use.Do not wish to be bound by any theory, the applicant think such technique effect owing to: cyclodextrin is by D(+)-glucopyranose is with α-1, the cyclic oligomer that 4-glycosidic bond joins end to end and forms, its molecule is wide at the top and narrow at the bottom, both ends open, hollow tubular article, intracavity portion is relative hydrophobicity, and all hydroxyls are then outside at molecule.Due to the molecular structure of this uniqueness of cyclodextrin, make the amino Portugal of cyclodextrin and carboxylic gather polysaccharide sodium and forms clathrate and do not show electrically charged, heat stability is high, thus reduces the sensitivity that colloidal solution changes variations in temperature and pH value.Result of study shows simultaneously, and the present invention has better antibacterial effect than single macromolecule glue body fluid.
The present invention gathers in the grinding step of the cyclodextrin clathrate of polysaccharide sodium and adds polyhydric alcohols if glycerol, xylitol, Sorbitol, propylene glycol, dexpanthenol are as promoter preparing the amino Portugal of carboxylic, can promote that the exchange of hydrone in polysaccharide sodium and cyclodextrin ring gathers in the amino Portugal of carboxylic, accelerate the generation that the cyclodextrin clathrate of polysaccharide sodium gathers in the amino Portugal of carboxylic.
Colloidal solution for wound reparation of the present invention is used for wound surface nursing, decomposition and the absorption of slough is accelerated in the debridement phase, the release of various somatomedin can be promoted at granulation tissue Formation period, stimulate the generation of blood capillary, in epithelization phase epidermis cell wet environment, the speed of dividing a word with a hyphen at the end of a line is faster, can healing acceleration.The present invention has the following advantages:
1, high water soluble, stability of solution is good, not by pH value and influence of temperature change;
2, anti-inflammation is effective;
3, good biocompatibility;
4, easy and simple to handle, be applicable to cleaning and the nursing of multiple wound.
Detailed description of the invention
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention
Embodiment 1
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 500) is 5%, alpha-cyclodextrin is 0.5%, dexpanthenol is 0.5%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and beta-schardinger dextrin-and dexpanthenol stir, and add Achates tank, grind 300 minutes under 80 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 40 DEG C of conditions, filter and remove insoluble matter, 120 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 2
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 400) is 4%, beta-schardinger dextrin-is 0.3%, xylitol is 0.2%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and beta-schardinger dextrin-and xylitol stir, and add Achates tank, grind 200 minutes under 70 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 50 DEG C of conditions, filter and remove insoluble matter, 130 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 3
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 300) is 1%, beta-schardinger dextrin-is 0.4%, glycerol is 0.1%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and beta-schardinger dextrin-and glycerol stir, and add Achates tank, grind 100 minutes under 70 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 20 DEG C of conditions, filter and remove insoluble matter, 140 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 4
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 200) is 3%, gamma-cyclodextrin is 0.2%, Sorbitol is 0. 2%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and gamma-cyclodextrin mixes Sorbitol and mixes evenly, adds Achates tank, grinds 90 minutes under 65 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 50 DEG C of conditions, filter and remove insoluble matter, 150 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 5
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 100) is 2%, gamma-cyclodextrin is 0.2%, xylitol is 0.1%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and gamma-cyclodextrin and xylitol stir, and add Achates tank, grind 60 minutes under 70 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 40 DEG C of conditions, filter and remove insoluble matter, 160 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 6
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 50) is 5%, gamma-cyclodextrin is 0.2%, propylene glycol is 0. 5%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, gamma-cyclodextrin propylene glycol and stirring, add Achates tank, grind 90 minutes under 60 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 50 DEG C of conditions, filter and remove insoluble matter, 120 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 7
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 100) is 2%, alpha-cyclodextrin is 0.3%, glycerol is 0. 4%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and alpha-cyclodextrin and glycerol stir, and add Achates tank, grind 60 minutes under 80 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 40 DEG C of conditions, filter and remove insoluble matter, 130 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 8
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 200) is 3%, alpha-cyclodextrin is 0.5%, Sorbitol is 0.3%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and alpha-cyclodextrin and Sorbitol stir, and add Achates tank, grind 90 minutes under 60 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 30 DEG C of conditions, filter and remove insoluble matter, 140 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 9
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 300) is 0.6%, alpha-cyclodextrin is 0.4%, dexpanthenol is 0.2%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and alpha-cyclodextrin and dexpanthenol stir, and add Achates tank, grind 60 minutes under 65 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 40 DEG C of conditions, filter and remove insoluble matter, 150 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Embodiment 10
Each component is got by following percentage by weight:
The amino Portugal of carboxylic gathers that polysaccharide sodium (degree of polymerization is 400) is 1%, alpha-cyclodextrin is 0.2%, propylene glycol is 0.1%, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal, and alpha-cyclodextrin and propylene glycol stir, and add Achates tank, grind 90 minutes under 75 DEG C of conditions;
The cyclodextrin clathrate (gathering polysaccharide sodium containing a small amount of amino Portugal of free carboxylic) amino for the carboxylic prepared Portugal being gathered polysaccharide sodium joins in normal saline, ultrasonic disperse 30 minutes under 40 DEG C of conditions, filter and remove insoluble matter, 160 DEG C of high-temperature vapour sterilizings, prepare a kind of colloidal solution repaired for wound.
Comparative example 1
Preparation containing the colloidal solution of cyclodextrin, is not produced by following percentage by weight:
It is 5% that polysaccharide sodium (degree of polymerization is 500) gathers in the amino Portugal of carboxylic, and all the other are normal saline.
Preparation method:
Polysaccharide sodium is gathered in amino for carboxylic Portugal to be joined in normal saline, and ultrasonic disperse 30 minutes under 40 DEG C of conditions, filters and remove insoluble matter, 120 DEG C of high-temperature vapour sterilizings, prepares a kind of not containing the colloidal solution of cyclodextrin.
Result of the test detects
1. Detection of Stability
The colloidal solution obtained by embodiment 1-10, carries out Detection of Stability with comparative example 1: the pH value changing colloidal solution, the stability change of observing colloid liquid simultaneously; Colloidal solution is left standstill 24h under room temperature (25 DEG C) and 5 DEG C of conditions, and (test and the stability result of colloidal solution is described as A, B and C Three Estate, A grade is fine dispersion to the stability change of observing colloid liquid, and obvious flocculation does not occur; For there is macroscopic slight flocculation in B grade, significantly flocculation occurs C).Stability result is presented in table 1 below.
Table 1: stability result
Sample stability |
The pH value changing colloidal solution is 5, leaves standstill 24h |
The pH value changing colloidal solution is 6.5, leaves standstill 24h |
The pH value changing colloidal solution is 7.5, leaves standstill 24h |
The pH value changing colloidal solution is 8.5, leaves standstill 24h |
24h is left standstill under room temperature (25 DEG C) condition |
24h is left standstill under 5 DEG C of conditions |
Embodiment 1 |
A |
A |
A |
A |
A |
A |
Embodiment 2 |
A |
A |
A |
A |
A |
A |
Embodiment 3 |
A |
A |
A |
A |
A |
A |
Embodiment 4 |
A |
A |
A |
A |
A |
A |
Embodiment 5 |
A |
A |
A |
A |
A |
A |
Embodiment 6 |
A |
A |
A |
A |
A |
A |
Embodiment 7 |
A |
A |
A |
A |
A |
A |
Embodiment 8 |
A |
A |
A |
A |
A |
A |
Embodiment 9 |
A |
A |
A |
A |
A |
A |
Embodiment 10 |
A |
A |
A |
A |
A |
A |
Comparative example 1 |
B |
C |
C |
C |
B |
C |
Can find out from result above and leave standstill 24 hours the pH value (pH=5) of wound after the skin and healing of the people of routine, the stability grade of the colloidal solution (gathering the cyclodextrin clathrate of polysaccharide sodium containing the amino Portugal of carboxylic) in embodiments of the invention 1-10 is A, and the stability grade of colloidal solution in comparative example 1 (namely not forming the cyclodextrin clathrate that polysaccharide sodium gathers in the amino Portugal of carboxylic) is B, and when pH environmental change is that 6.5-8.5 (pH value namely in wound healing process or after being infected) leaves standstill 24 hours afterwards, the stability grade of the colloidal solution in embodiments of the invention 1-10 is still A, and the colloidal solution grade in comparative example 1 is reduced to C further.Therefore, under pH value (pH=6.5-8.5) under the skin of people and the conventional pH value (pH=5) of the rear wound of healing and in wound healing process or after being infected, the stability grade of colloidal solution of the present invention is all better than the colloidal solution of comparative example 1, wherein when environment for use becomes the pH value in wound healing process or after being infected, colloidal solution of the present invention is more remarkable relative to the stability superiority of comparative example 1.
In addition, 24 hours are left standstill under room temperature environment, the stability grade of colloidal solution in embodiments of the invention 1-10 (gathering the cyclodextrin clathrate of polysaccharide sodium containing the amino Portugal of carboxylic) is A, and the stability grade of colloidal solution (namely not forming the cyclodextrin clathrate that polysaccharide sodium gathers in the amino Portugal of carboxylic) in comparative example 1 is B.And when ambient temperature becomes 5 DEG C, the stability grade of colloidal solution of the present invention is still A, and the colloidal solution grade in comparative example 1 is reduced to C further.Visible at room temperature with change after ambient temperature (such as 5 DEG C) under, the stability grade of colloidal solution of the present invention is all better than the colloidal solution of comparative example 1, wherein when ambient temperature changes, colloidal solution of the present invention is more remarkable relative to the stability superiority of comparative example 1.
2. fungistatic effect
The colloidal solution of the colloidal solution obtained by embodiment 1-10 and comparative example 1 carries out inhibitory effect checkout facility according to the following suspension method that adopts.
Test organisms is Candida albicans, escherichia coli and staphylococcus aureus, gets its 3-14 for ordinary nutrient agar fresh cultured thing, and making bacteria containing amount with the PBS buffer containing 10g/L peptone is 1 × 10
6-2 × 10
6the bacteria suspension of cfu/mL.When bacteria suspension and colloidal solution are 2:1, act on 10 minutes, the colloidal solution of the embodiment of the present invention 1-10 bacteriostasis rate to Candida albicans, escherichia coli and staphylococcus aureus all reaches 100%, and the colloidal solution of comparative example 1 is also 100% to the bacteriostasis rate of above-mentioned antibacterial.When bacteria suspension and colloidal solution are 4:1, act on 10 minutes, the colloidal solution of the embodiment of the present invention 1-10 bacteriostasis rate to Candida albicans, escherichia coli and staphylococcus aureus all reaches 100%, and the bacteriostasis rate of the colloidal solution of comparative example 1 to above-mentioned antibacterial is reduced to 99.99%.When bacteria suspension and colloidal solution are 8:1, act on 10 minutes, the colloidal solution of the embodiment of the present invention 1-10 bacteriostasis rate to Candida albicans, escherichia coli and staphylococcus aureus all reaches 99.99%, and the colloidal solution of comparative example 1 to the bacteriostasis rate of above-mentioned antibacterial for be reduced to 99% further.
As can be seen here, the colloidal solution (gathering the cyclodextrin clathrate of polysaccharide sodium containing the amino Portugal of carboxylic) that embodiment 1-10 obtains has better fungistatic effect compared to the colloidal solution (namely not forming the cyclodextrin clathrate that polysaccharide sodium gathers in the amino Portugal of carboxylic) of comparative example 1.
3 treatment of wounds effects
The colloidal solution obtained by embodiment 1-10 is applied to burn wound's clinical care, also namely as colloidal solution treatment group.Adopt comparative example 1 as colloidal solution matched group, respectively soak process is carried out to wound, adopt comparative example 1 colloidal solution art in and postoperative method with dispose with in the art of colloidal solution treatment group with postoperative method with dispose identical.
Clinical observation result be colloidal solution treatment group comparatively matched group ooze out less, wound contraction is faster.Colloidal solution treatment group granulation is fresh, edema light, in clinical observation, does not show toxicity, zest, irritated and pyrogenicity reaction, safe and reliable, easy to use.