CN102008740B - Absorbable growth factor composite dressing - Google Patents
Absorbable growth factor composite dressing Download PDFInfo
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- CN102008740B CN102008740B CN201010573016.3A CN201010573016A CN102008740B CN 102008740 B CN102008740 B CN 102008740B CN 201010573016 A CN201010573016 A CN 201010573016A CN 102008740 B CN102008740 B CN 102008740B
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Abstract
The invention relates to an absorbable growth factor composite dressing which is mainly prepared from compound cellulose and growth factors, wherein the compound cellulose is prepared by compounding modified hydroxyethylcellulose and sodium alga acid. The dressing is prepared by compounding the modified hydroxyethylcellulose and the sodium alga acid to prepare the compound cellulose and then adding 0.02-0.05% of freeze-dried growth factor powder, and evenly mixing the compound cellulose with the powder. The dressing can promote rapid wound healing, shorten the treatment period and can be widely applied to various wounds comprising internal wounds and external wounds.
Description
Technical field
The present invention relates to a kind of medical dressing, particularly one can absorb somatomedin combine dressing, belongs to medical dressing technical field.
Background technology
Often can, to human body because operation or the physical damnification causing of injuring unexpectedly carry out local hemostasis, and prevent that wound surface is infected, the healing of accelerated in wounds clinically.About hemostasis and the healing of wound, people find that wound surface covering dressing does not more cover healing effect and will get well very early, so people conduct in-depth research dressing, successively once there is dissimilar dressing, wherein traditional gauze class dressing is the most influential, and the time of application is the longest, the share accounting on market is also larger.
Along with the fast development of modern science and technology and developing rapidly of each technical field, the traditional dressing that plays simple covering effect can not meet clinical needs.Traditional dressing is main material mainly with gauze, cotton pad; can play the effect of protection wound surface; cost compare is cheap; raw material sources are more extensive; reusable; but because of its haemostatic effect bad; without wound surface moisture-keeping function; granulation is easily grown into and is generated adhesion incrustation in gauze mesh; in the process of changing dressings, cause cambium damage, patient is quite painful, simultaneously because the skin wound healing phase is long, wound cicatrix is obvious; therefore the Medical dressing for skin wound of, developing a kind of shortcoming that can reduce traditional absorbent cotton has certain clinical value.For this reason, many research worker conduct in-depth research this, have worked out dissimilar wound surface medical dressing.Show according to related data, the dressing of exploitation is at present divided into biological dressing, synthetic dressing, somatomedin dressing, organizational project Wound dressing and nanometer dressing etc., all in the development that has promoted in varying degrees medical dressing technology.
Since the eighties, about the research of somatomedin to repair in trauma effect, the basic change that made the noegenesis of people to wound repair, adopt this kind of dressing not only can repair surface wound but also can repair internal organs and whole body, can accelerate the healing of wound surface, therefore the research of somatomedin dressing is become the focus of tissue repair research in recent years simultaneously.Chinese patent: 99100585.6, name is called the sponge material that " promoting sponge material its preparation method and the application of spinal cord tissue wound healing " studied a kind of mixture by collagen protein or collagen protein and chitin and added FGF-2m and nerve growth factor, adopt this sponge material can accelerate damaged tissues wound or injured 's healing, healing effect is good, but because adopting collagen protein, this material adopts animal collagen more, easily produce temperature-sensitive phenomenon, this patent adopts the aqueous solution that contains somatomedin to sneak in the mixed mechanism of collagen protein and chitin simultaneously, then carrying out lyophilization forms.The growth factor activity half-life only has a few hours or shorter, owing to being simple mixing, the somatomedin that sponge material surface exists, contact with the external world, cause the biologically active labile of somatomedin, and the Degradation of the protease of wound site existence to somatomedin, easily make somatomedin lose its biological activity.For overcoming the defect of above-mentioned technology, so the application's applicant is in order to address the above problem, research and develop a kind of Medical dressing, adopt natural modified hydroxyethylcellulosadsorbing and the composite blended fiber of Na-alginate as polymer carrier, adopt the release of the matrix embedding techniques retarding of growing factor, make matrix good dispersion, envelop rate is higher.And be widely used in various wounds, and comprising surgical incision, the wound surface such as the shallow II degree of burning, the diseased region of II degree, and skin-grafting area deeply, skin donor site, ulcer, are a kind of Medical dressings evident in efficacy.
Summary of the invention
The object of this invention is to provide a kind of somatomedin combine dressing that can overcome temperature-sensitive phenomenon and can promote wound surface quickly-healing.
In order to address the above problem, reach above-mentioned goal of the invention, the technical solution adopted in the present invention is:
Somatomedin combine dressing is mainly by modified hydroxyethylcellulosadsorbing and the composite blended fiber element of making of sodium alginate, i.e. composite fibre, adds somatomedin composition.
Somatomedin may be selected to fibroblast growth factor, epidermal growth factor, nerve growth factor and Connective Tissue Growth Factor etc.
The preferred recombination human basic fibroblast growth factor RH-bFGF of somatomedin.
The preferred lyophilized powder of somatomedin, its addition is the 0.02%-0.05% of composite fibre total amount.
The composite weight ratio of modified hydroxyethylcellulosadsorbing and sodium alginate is 5～15: 5～15.
Above-mentioned composite fibre is prepared by following preparation method:
(1) with deionized-distilled water, sodium alginate being mixed with to quality percentage composition is 8～15% sodium alginate soln a, and mix homogeneously;
(2) hydroxyethyl-cellulose of modification being mixed with to quality percentage composition with deionized water is 10～20% modified hydroxyethylcellulosadsorbing solution b, mix homogeneously;
(3) by solution a and solution b mix homogeneously, stir 15～20min, vacuum defoamation, is undertaken by wet spinning process, solidifies and can make compound blended fiber.
Above-mentioned somatomedin adopts physics matrix investment to sneak into composite fibre.
Above-mentioned physics matrix investment is as follows:
In recent years, become the new highlight of medical dressing field development containing somatomedin wound dressing.It has not only overcome the single shortcoming of traditional dressing performance, and also make dressing increase wound healing, improve effect of wound healing effect adding of somatomedin.
The most frequently used method is microsphere investment at present, and somatomedin is dissolved or is dispersed in polymeric matrix, utilizes two emulsion methods can form the microsphere that particle diameter is 1～40um.Because microsphere size is little, the large and surface of specific surface area, inner performance difference be larger, the rate of release that the method can the growth regulation factor, realizes long-acting object, can protect again somatomedin to avoid being destroyed simultaneously.But in microsphere preparation process, somatomedin may directly contact with organic solvent and cause degeneration, easily assembles between microsphere simultaneously.
For solving the problem of above existence, we adopt the preparation of polymeric biomaterial matrix embedding techniques, we are through test of many times, the shortcoming of preparing for the microsphere embedding techniques overcoming in the past, adopt polymeric biomaterial matrix embedding techniques to delay the release of RH-bFGF somatomedin, make matrix good dispersion, envelop rate is higher.
Modified hydroxyethylcellulosadsorbing and sodium alginate blended fiber are inserted in accurate electronic stirrer, and at room temperature high-speed stirred 1h, obtains the powder body 100g of blended fiber, lyophilizing, and-20 ° are continued to stir after preserving 10min, need repeatable operation 5 times.In the time operating the 3rd time, the RH-bFGF somatomedin lyophilized powder solution of 2ml is inserted in aerosol apparatus, when the powder body of composite fibre stirs, to its sprinkling, atomization, so that RH-bFGF somatomedin lyophilized powder solution incorporates the matrix of composite fibre completely, the matrix of blended fiber is met water and is immersed and can expand rapidly, after expansion, form network gel at blended fiber matrix surface, form an airtight depletion of QI oxygen environmental activity, can effectively be hedged off from the outer world and can keep to greatest extent the activity of somatomedin; Until mix and blend has operated for 5 times.Lyophilization, until moisture content volatilizees completely ,-20 ° of preservations, prepare the omnidistance sterile working of noting.
Sodium alginate and modified hydroxyethylcellulosadsorbing blended fiber molecule are the tridimensional network having good stability, and the alkaline RH-bFGF somatomedin contrary with charge forms comparatively stable by interionic interaction, form certain affinity between the two, RH-bFGF somatomedin lyophilized powder solution is adsorbed and is wrapped in matrix by sodium alginate and modified hydroxyethylcellulosadsorbing blended fiber powder, along with the degraded of sodium alginate and modified hydroxyethylcellulosadsorbing blended fiber, realize the control in vivo of RH-bFGF somatomedin and discharge.
It is neutral that modification hydroxy ethyl fiber belongs to, and has its unique advantage than the modified fibre of other acidic-group.The anthemorrhagic performance of modified hydroxyethylcellulosadsorbing and absorbent properties depend on its water solublity, and water solublity is better, and water suction is faster, hemostasis is faster, absorbs also faster.The water solublity quality of sodium alginate and modified hydroxyethylcellulosadsorbing blended fiber, except the physical property of itself, the more important thing is the substituent hydrophilic of introducing in the time carrying out chemical modification.In numerous water-soluble celluloses, there is stronger hydrophilic with modified hydroxyethylcellulosadsorbing.Thereby modified hydroxyethylcellulosadsorbing is minimum to adding the compatibility restriction of various medicines owing to being nonionic cellulose derivative in addition, is easily used in conjunction with various antiinflammatory, hemostasis, anti-infective medicine.Have high dissolubility, high-hydroscopicity, hemostasis fast, absorb also soon, and all can not produce negative effect to adding various medicines.
RH-bFGF somatomedin is a kind of multi-functional cell growth factor to various wound surface, can stimulate the propagation of mesoderm and ectoderm derived cell, has and promotes tissue regeneration, stimulation new vessels to form, improve blood circulation, accelerate the function of damaged tissue repair.
RH-bFGF somatomedin produces plerosis function by three aspects::
(1) somatomedin is as chemical chemoattractant chemotactic inflammatory cell and tissue repair cell, for wound surface sterilization and later stage repair and create conditions;
(2) directly act on the growth factor receptors on tissue repair cell, accelerate cell cycle by its short division effect and change, accelerate to stretch out face reparation;
(3) by competitiveness effect, can raise the activity of growth factor receptors on tissue repair cell, thus the transmission of signal for faster.
The shortcoming of RH-bFGF somatomedin:
Because RH-bFGF somatomedin is all unstable to heat and acid, easily by enzyme hydrolysis, half-life is in vivo short, only have 3～5min, part or whole body application can be difficult to bring into play its biological effect by quick inactivating, and bioavailability is low, effect is undesirable, thereby cause clinical practice limited, can not generally be promoted, how making RH-bFGF somatomedin continue to bring into play efficiently its biological action becomes current key issue urgently to be resolved hurrily.Therefore, RH-bFGF growth factor slow-release system (control and discharge), becomes best solution.
Adopt medicine control releasing mechanism:
Adopt natural sodium alginate and the modified hydroxyethylcellulosadsorbing blended fiber polymer carrier as RH-bFGF somatomedin, because alginic acid and modified hydroxyethylcellulosadsorbing belong to neutral base material, first solve unstable in application of RH-bFGF somatomedin.And the RH-bFGF somatomedin half-life is in vivo short, only there is 3～5min, part or whole body application can be difficult to bring into play its biological effect by quick inactivating, bioavailability is low, effect is undesirable, thus must adopt material controlled release, along with the degraded of carrier material, by RH-bFGF growth factor release out, the rate of release of RH-bFGF somatomedin lyophilized powder is by regulating the degradation speed control of carrier matrix.The advantage of this control delivery is that RH-bFGF somatomedin is used up rear carrier matrix and is also degraded and absorbed, and takes out without second operation.There is not chemical reaction in RH-bFGF somatomedin and carrier material simultaneously, RH-bFGF growth factor release speed is slack-off, the long-acting constant that can realize RH-bFGF somatomedin discharges, will play crucial effect in wound repair like this, RH-bFGF somatomedin can make cell proliferation, comprises angiogenesis and fibroblast proliferation.RH-bFGF somatomedin can stimulate secretion of epidermal growth factor, thereby promotes the growth of epidermis cell.Shallow degree wound healing mainly relies on epithelization, exogenous RH-bFGF somatomedin can promote the expression of endogenous RH-bFGF, vascular endothelial cell, vascular smooth muscle cell are bred rapidly, improve local microcirculation, play epithelization and acceleration and stretch out the effect that face heals.In deep wounds healing, RH-bFGF somatomedin mainly promote the to heal epithelial cell proliferation of the later stage appendages of skin.Meanwhile, external RH-bFGF somatomedin can activate the active of Endogenous Growth Factors or raise its expression of receptor, and then promotes the reparation of the residual wound of burn.Residual wound infects and easily causes wound contraction to suppress, and RH-bFGF somatomedin can be removed this inhibitory action, shows biological effect widely in wound healing, also has considerable value in the clinical practice of burn treating.
The invention has the advantages that:
1. accelerate healing speed, shorten treatment time;
2. under dressing, the environment pH value of wound surface, humidity are suitable, are conducive to the healing of wound;
3. there is no thermosensitive response, safe, nontoxic, the compatibility is good;
4. can promote the growth of epidermis cell;
5. the present invention adopts the technology powder body processing of lyophilized powder, can keep to greatest extent the activity of somatomedin;
6. modified hydroxyethylcellulosadsorbing and sodium alginate combine dressing, sodium alginate has extremely strong absorbability while use separately, can absorb the liquid that is equivalent to 20 times of sole masses, form hydrogel in wound surface, can not only provide moistening environment to wound healing, and be biodegradable gradually in sepage at wound healing process, on wound surface, do not have fiber residual, in the time that it contacts with wound exudate, generate the sodium alginate of solubility by ion exchange, the calcium ion displacing can be transformed into fiber the sodium alginate soln of viscosity slowly, newborn does not organize and can again damage because of the adhesion of dressing, can accelerate wound surface hemostasis.Pliable and tough, compliance good, but while use separately, adhesion is poor, composite with modified hydroxyethylcellulosadsorbing, can increase its adhesive function and haemostatic effect, reach synergism.When combine dressing contacts with blood, can adsorb moisture a large amount of in blood and wound surface form hydrogel, somatomedin plays the slowly effect of slow release by the complex carrier of hydrogel, thereby plays long-acting repair function;
7. the rate of release of somatomedin lyophilized powder is controlled by the degradation speed that regulates carrier matrix, the advantage of this control delivery is, somatomedin is used up rear carrier matrix and is also degraded and absorbed, take out without second operation, growth factor release speed is slack-off, and the long-acting constant that can realize somatomedin discharges.
Detailed description of the invention
Below by embodiment, the present invention is described in further details, these embodiment are only used for illustrating the present invention, do not limit the scope of the invention.
Embodiment 1
Combine dressing is by modified hydroxyethylcellulosadsorbing and the sodium alginate composite blended fiber of making of example 5～15: 5～15 in mass ratio, at room temperature high-speed stirred 1h, obtain the powder body of blended fiber, stirring simultaneously, to 0.02～0.05% RH-bFGF somatomedin lyophilized powder solution of its rapid atomized spray compound cellulose total amount, so that RH-bFGF somatomedin lyophilized powder solution incorporates the matrix of composite fibre completely, the matrix of blended fiber is met water and is immersed and can expand rapidly, after expansion, form network gel at blended fiber matrix surface, form an airtight depletion of QI oxygen environment, can effectively be hedged off from the outer world and can keep to greatest extent the activity of somatomedin, make RH-bFGF somatomedin be embedded in matrix inside, then lyophilization, until moisture content volatilizees completely, complete matrix embedding.
Modified hydroxyethylcellulosadsorbing and sodium alginate blended fiber form the mechanical strength of matrix, the composition part by weight of modified hydroxyethylcellulosadsorbing and the shared blended fiber of sodium alginate when physics and chemistry and biological property all depend on matrix embedding, RH-bFGF somatomedin factor of shared total amount ratio when embedding in matrix.
(1) modified hydroxyethylcellulosadsorbing and sodium alginate blended fiber, wherein the shared ratio of sodium alginate is excessive, can make the matrix concentration of formation larger, cause the matrix of formation tight, permeability is less, somatomedin lyophilized powder is more difficult for entering matrix inside, and the activity recovery of somatomedin is just low.Otherwise the shared mass ratio of the sodium alginate in blended fiber is too small, also can make the concentration of the intermolecular physical crosslinking point of modified hydroxyethylcellulosadsorbing and sodium alginate reduce, somatomedin lyophilized powder enters after matrix, and controlled release is too fast, the weak effect reaching.So we think that adopting modified hydroxyethylcellulosadsorbing and the composite weight ratio of sodium alginate is at 5～15: 5～15 o'clock, are ideal.The intermolecular formation hydrogen bond network of modified hydroxyethylcellulosadsorbing and sodium alginate is crosslinked, the probability that entanglement occurs between macromolecular chain is increased, the concentration that forms intermolecular physical crosslinking point also increases, produce Van der Waals interaction force between the two, active force between molecule increases, and forms the combination of fiber.Modified hydroxyethylcellulosadsorbing add the entanglement compactness having reduced between macromole, can improve fibrous inside molecule crosslinked, reduced alginate fibre and generated the probability of skin-core structure.
(2) be embedded in the RH-bFGF somatomedin in blended fiber matrix, because blended fiber three dimensional structure is by loose, make it be easy to enter in matrix, liquid causes the expansion of matrix, makes RH-bFGF somatomedin be embedded in matrix inside.Through many experiments, draw and add 0.02～0.05% RH-bFGF somatomedin lyophilized powder solution of compound cellulose total amount can incorporate the matrix inside of composite fibre completely, carry out matrix embedding, be ideal.
Embodiment 2
The 0.05%RH-bFGF somatomedin lyophilized powder that contains compound cellulose total amount with account for 5～15: 5～15 modified hydroxyethylcellulosadsorbings of total amount and the composite combine dressing of making of sodium alginate (hereinafter to be referred as: can absorb somatomedin combine dressing) haemostatic effect.
Get 10 of healthy mices (Dongguan medicine inspecting institute provides), body weight 100～120g, is divided into 2 groups at random, every group each 5: (1) test group (can absorb somatomedin combine dressing); (2) matched group (common antiseptic gauze).With anesthetis, white mice is anaesthetized to injection, manufacture the hemorrhage wound surface of 1cm × 0.5cm size at its back, will after test group folding of material, apply on wound surface and stop blooding, compare with common antiseptic gauze simultaneously, record bleeding stopping period.
Result:
Test group bleeding stopping period is 1.85 (min), matched group is 5.35 (min), two groups of significant differences, test group bleeding stopping period shortens 65%, show to absorb somatomedin dressing and there is obvious anastalsis, haemostatic effect, be all better than matched group with the adhesive capacity of wound, and can degradation in vivo absorb, therefore, be a kind of comparatively ideal wound hemostasis material.
Embodiment 3
The 0.05%RH-bFGF somatomedin lyophilized powder that contains compound cellulose total amount with account for 5～15: 5～15 modified hydroxyethylcellulosadsorbings of total amount and the composite combine dressing of making of sodium alginate (hereinafter to be referred as: can absorb somatomedin combine dressing) repairing effect.
Get 10 of healthy mices (Dongguan City medicine inspecting institute provides), body weight 100～120g.With anesthetis, white mice is anaesthetized to injection, manufacture the hemorrhage wound surface of 1cm × 0.3cm × 0.3cm size at its back, can absorb after somatomedin dressing folds and apply on wound surface, add less compressing.
Viewing test group, 1 day, 4 days, 7 days, 10 days, can absorb somatomedin dressing reparation situation in vivo:
Note: 1. outward appearance is complete, not degraded +++; Outward appearance is imperfect, Partial digestion ++; Outward appearance is unclear, most of degraded+; Basic absorption-.
2. wound healing degree: 1%-100%
This shows, the biocompatibility that can absorb somatomedin combine dressing is good, can promote wound healing, because RH-BFGF somatomedin can stimulate secretion of epidermal growth factor, thereby promotes the growth of epidermis cell.
Embodiment 4
The 0.05%RH-bFGF somatomedin lyophilized powder that contains compound cellulose total amount with account for 5～15: 5～15 modified hydroxyethylcellulosadsorbings of total amount and the composite combine dressing of making of sodium alginate (hereinafter to be referred as: can absorb somatomedin combine dressing) water-soluble test:
Can absorb somatomedin combine dressing and be seated in glass drying oven, splash into the normal saline of 60ml, time record that visual observations is dissolved.Repeated trials 3 times, and record result.
Result shows: whole dissolution times that can absorb somatomedin combine dressing are 1.6 (min), can absorb as can be seen here somatomedin combine dressing and can absorb completely in vivo, and have safety.
Claims (2)
1. can absorb a somatomedin combine dressing, it is characterized in that this combine dressing is mainly made up of modified hydroxyethylcellulosadsorbing and the composite compound cellulose of making of sodium alginate and recombination human basic fibroblast growth factor RH-bFGF, described recombination human basic fibroblast growth factor RH-bFGF adopts physics matrix investment to sneak into compound cellulose, described physics matrix investment is as follows: modified hydroxyethylcellulosadsorbing and sodium alginate composite fiber element are inserted in accurate electronic stirrer, at room temperature high-speed stirred 1h, obtains the powder body 100g of compound cellulose, lyophilizing, after-20 ° of preservation 10min, continue to stir, need repeatable operation 5 times, in the time operating the 3rd time, fast the recombination human basic fibroblast growth factor RH-bFGF lyophilized powder solution of 2mL is inserted in aerosol apparatus, when the powder body of compound cellulose stirs, to its sprinkling, atomization, observe, so that recombination human basic fibroblast growth factor RH-bFGF lyophilized powder solution incorporates the matrix of compound cellulose completely, the matrix of compound cellulose is met water and is immersed and can expand rapidly, after expansion, form network gel at compound cellulose matrix surface, form an airtight no oxygen environmental activity, can effectively be hedged off from the outer world, until mix and blend has operated for 5 times, lyophilization, until moisture volatilizees completely,-20 ° of preservations, prepare omnidistance sterile working.
2. one according to claim 1 can absorb somatomedin combine dressing, and the compound cellulose described in it is characterized in that is prepared by following preparation method:
(1) with deionized-distilled water, sodium alginate being mixed with to quality percentage composition is 8～15% sodium alginate soln a, and mix homogeneously;
(2) modified hydroxyethylcellulosadsorbing being mixed with to quality percentage composition with deionized-distilled water is 10～20% modified hydroxyethylcellulosadsorbing solution b, mix homogeneously;
(3) by solution a and solution b mix homogeneously, stir 15～20min, vacuum defoamation, is undertaken by wet spinning process, solidifies and can make compound cellulose.
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| CN105963772A (en) * | 2016-07-06 | 2016-09-28 | 江苏达胜伦比亚生物科技有限公司 | Medical cold application patch containing irradiation crosskinked growth factor hydrogel |
| CN107185025A (en) * | 2017-05-26 | 2017-09-22 | 吉林大学 | A kind of Chinese medicine nanometer spinning composite cellulosic membrane dressing, preparation method and applications |
| CN109248333B (en) * | 2018-11-08 | 2021-06-18 | 广州润虹医药科技股份有限公司 | Medical dressing for resisting bacteria and promoting wound healing and preparation method and application thereof |
| CN109627498A (en) * | 2018-11-27 | 2019-04-16 | 青岛大学 | A kind of sodium alginate-cellulose derivative blended membrane/fiber and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1228339A (en) * | 1999-02-04 | 1999-09-15 | 李校坤 | Sponge material capable of promoting spinal cord tissue wound healing, its preparing method and use |
| EP1206271B1 (en) * | 1999-07-22 | 2004-09-15 | Deroyal Industries, Inc. | Composition and method for enhancing wound healing |
| CN101569758A (en) * | 2008-12-31 | 2009-11-04 | 褚加冕 | Preparation method for medical use hydrocolloid dressing |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1228339A (en) * | 1999-02-04 | 1999-09-15 | 李校坤 | Sponge material capable of promoting spinal cord tissue wound healing, its preparing method and use |
| EP1206271B1 (en) * | 1999-07-22 | 2004-09-15 | Deroyal Industries, Inc. | Composition and method for enhancing wound healing |
| CN101569758A (en) * | 2008-12-31 | 2009-11-04 | 褚加冕 | Preparation method for medical use hydrocolloid dressing |
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Effective date of registration: 20171108 Address after: 529300 Guangdong city of Jiangmen province Kaiping city West Lake West Tsui lake two Road No. 1 East 2 Patentee after: Guangdong Honghe Medical Technology Co., Ltd. Address before: 510150 room 144, 610 Huang Sha Avenue, Guangzhou, Guangdong, Liwan District Patentee before: Wu Tao |
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