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CN109966556B - A kind of natural polyphenol-pluronic gel and preparation method thereof - Google Patents

A kind of natural polyphenol-pluronic gel and preparation method thereof Download PDF

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CN109966556B
CN109966556B CN201910267198.2A CN201910267198A CN109966556B CN 109966556 B CN109966556 B CN 109966556B CN 201910267198 A CN201910267198 A CN 201910267198A CN 109966556 B CN109966556 B CN 109966556B
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tannic acid
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polyoxyethylene polyoxypropylene
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王宇
程义云
滕红林
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First Affiliated Hospital of Wenzhou Medical University
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Abstract

本发明利用一种天然多酚‑普兰尼克凝胶,其由天然多酚化合物——单宁酸以及商业化的聚合物——聚氧乙烯聚氧丙烯醚嵌段共聚物通过氢键作用形成三维凝胶结构,单宁酸结构中的大量锚根使得合成的凝胶具有良好的粘性,且单宁酸已被广泛证明具有清除氧自由基和抗氧化的特性,并且提供上述天然多酚‑普兰尼克凝胶的制备方法。

Figure 201910267198

The present invention utilizes a natural polyphenol-pluronic gel, which is composed of a natural polyphenol compound—tannic acid and a commercialized polymer—polyoxyethylene polyoxypropylene ether block copolymer through hydrogen bonding to form a three-dimensional Gel structure, a large number of anchor roots in the tannic acid structure make the synthesized gel have good viscosity, and tannic acid has been widely proven to have oxygen free radical scavenging and antioxidant properties, and provide the above-mentioned natural polyphenol-Pram Preparation of Nickel Gel.

Figure 201910267198

Description

Natural polyphenol-Pluronic gel and preparation method thereof
Technical Field
The invention relates to the technical field of medical materials, in particular to a gel system, and specifically relates to a natural polyphenol-pluronic gel and a preparation method thereof.
Background
Dural tears or defects are a troublesome problem often encountered in neurosurgery and spinal surgery. Early repair after dural injury is critical because cerebrospinal fluid leakage from dural opening can cause a series of serious complications such as local wound healing difficulties, epidural infection, arachnoiditis, intracranial infection and even death. Currently, the most widely used method for repairing dura mater in clinic is direct suturing. However, dural sutures are not only technically demanding and time consuming, but often do not achieve a tight seal of the dura mater. Dural sealants with tissue adhesive capabilities are also emerging clinically for direct adhesive fixation of implanted dural substitutes or to enhance the sealing of dural sutures. However, fibrin glue which is currently applied to clinical practice has weak bonding strength, high price, complicated preparation and possible risks of virus transmission and anaphylactic reaction. While other chemically synthesized gels have drawbacks such as water swelling in vivo, neurotoxicity, and the like. There is therefore still a clinical need for more optimal performance or cost-effective dural sealants.
On the other hand, acute spinal cord injury is often a more concern in spinal surgery requiring epidural repair. Acute spinal cord injury can cause serious physical disability and even death, and brings heavy economic burden and mental burden to patients and families, and is a social problem which cannot be ignored. The existing treatment for spinal cord injury is lack of effective and reliable treatment means except for surgical nerve decompression. Therefore, the multifunctional gel which has the functions of protecting nerves, promoting the recovery of nerve functions and adhering and sealing dura mater tissues is designed and developed, and has very important clinical application value.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the multifunctional gel which has the functions of protecting nerves, promoting the recovery of nerve functions and adhering and sealing dura mater tissues.
In order to achieve the above object, the present invention provides a natural polyphenol-pluronic gel, which is a copolymer formed by copolymerizing tannic acid and polyoxyethylene polyoxypropylene ether block copolymer, and the chemical structural formula of the copolymer is as follows:
Figure GDA0002044450510000021
as a further improvement of the invention, the molar ratio of the tannic acid to the polyoxyethylene polyoxypropylene ether block copolymer is 33.2: 1.
As a further improvement of the invention, the number average molecular weight of the tannic acid is 500-5000 Da.
In a further improvement of the present invention, the number average molecular weight of the polyoxyethylene polyoxypropylene ether block copolymer is 1000-20000 Da.
The invention also provides a preparation method of the natural polyphenol-pluronic gel, which comprises the following steps:
1) dissolving tannic acid in double distilled water to form a tannic acid solution with the concentration of 50% (w/w);
2) dissolving polyoxyethylene polyoxypropylene ether block copolymer in double distilled water at 0-8 ℃ to form polyoxyethylene polyoxypropylene ether block copolymer solution with the concentration of 20% (w/w);
3) mixing and fully shaking the tannic acid solution and the polyoxyethylene polyoxypropylene ether segmented copolymer solution in the first step and the second step, wherein the volume ratio of the tannic acid solution to the polyoxyethylene polyoxypropylene ether segmented copolymer solution is 1: 0.2-5, then centrifuging to remove the supernatant, and preparing the natural polyphenol-pluronic gel.
The invention has the following advantages: the invention utilizes a natural polyphenol compound, namely tannic acid, and a commercial polymer, namely polyoxyethylene polyoxypropylene ether block copolymer to form a three-dimensional gel structure through hydrogen bond action, a large number of anchor roots in the tannic acid structure enable the synthesized gel to have good viscosity, and the tannic acid has the characteristics of scavenging oxygen free radicals and resisting oxidation, can block the secondary pathological process after acute spinal cord injury, and plays a role in neuroprotection.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of a synthetic natural polyphenol-Pluronic gel according to example 1 of the present invention;
FIG. 2 is a Fourier transform infrared spectrum characterization of synthetic natural polyphenol-Pluronic gel according to example 1 of the present invention;
FIG. 3 shows the result of measuring the dynamic viscosity of the synthetic natural polyphenol-Pluronic gel according to the present invention;
FIG. 4 is a graph showing the results of the adhesive strength of the synthetic natural polyphenol-Pluronic gel and fibrin glue on in vitro porcine dural tissue;
FIG. 5 is a schematic structural diagram of a water seal performance testing device;
FIG. 6 is a schematic diagram showing the water-sealing performance test results of the synthetic natural polyphenol-Pluronic gel and fibrin glue on in vitro porcine dura mater tissues;
FIGS. 7(a) and (b) are graphs comparing the performance of the synthetic natural polyphenol-Pluronic gel and fibrin glue of the present invention on a repair model of a simple suture model of a rabbit dura mater injury model;
FIGS. 8(a) and (b) are graphs comparing the performance of the synthetic natural polyphenol-Pluronic gel and fibrin glue of the present invention on a repair model of a fascia graft model of a rabbit dural injury model;
FIG. 9 is a graph showing the results of the ability of the natural polyphenol-Pluronic gel and fibrin glue of the present invention to promote dural tissue healing in a repair model of a fascia graft model of a rabbit dural injury model;
FIG. 10 shows the content variation of MDA and SOD in the synthetic natural polyphenol Pluronic gel of the present invention in the model of treating rat spinal cord injury, wherein 10(a) is the content variation of MDA, and 10(b) is the content variation of SOD;
FIG. 11 is a graph showing the effect of synthetic natural polyphenol-Pluronic gel on the recovery of neurological function in a model of treating spinal cord injury in rats, wherein 11(a) is a schematic diagram showing the scoring result of hind limb motor function; wherein 11(b) is a diagram showing the scoring result of the bladder autonomous urination function; wherein 11(c) is a spinal cord tissue staining image of a rat spinal cord injury model repair model; wherein 11(d) is a spinal cord tissue neuron cell staining image of a rat spinal cord injury model repair model.
Detailed Description
The present invention will be described in further detail with reference to the drawings, examples and effect examples, but the scope of the present invention is not limited thereto.
In the application, the abbreviation of tannic acid is named TA, the abbreviation of polyoxyethylene polyoxypropylene ether block copolymer is named PF127, the abbreviation of natural polyphenol-Pluronic gel is named TA-PF127 gel, TA appearing hereinafter is equivalent to tannic acid, PF127 is equivalent to polyoxyethylene polyoxypropylene ether block copolymer, and TA-PF127 gel is equivalent to natural polyphenol-Pluronic gel.
EXAMPLE 1 preparation of Natural Polyphenol-Pluronic gel
1) Dissolving tannic acid in double distilled water to form a tannic acid solution with the concentration of 50% (w/w);
2) dissolving polyoxyethylene polyoxypropylene ether block copolymer in double distilled water at 4 ℃ to form polyoxyethylene polyoxypropylene ether block copolymer solution with the concentration of 20% (w/w);
3) mixing and fully shaking the tannic acid solution and the polyoxyethylene polyoxypropylene ether segmented copolymer solution in the first step and the second step, wherein the volume ratio of the tannic acid solution to the polyoxyethylene polyoxypropylene ether segmented copolymer solution is 1: 1, then centrifuging to remove the supernatant, and preparing the natural polyphenol-pluronic gel.
EXAMPLE 2 preparation of Natural Polyphenol-Pluronic gel
1) Dissolving tannic acid in double distilled water to form a tannic acid solution with the concentration of 50% (w/w);
2) dissolving polyoxyethylene polyoxypropylene ether block copolymer in double distilled water at 4 ℃ to form polyoxyethylene polyoxypropylene ether block copolymer solution with the concentration of 20% (w/w);
3) mixing and fully shaking the tannic acid solution and the polyoxyethylene polyoxypropylene ether segmented copolymer solution in the first step and the second step, wherein the volume ratio of the tannic acid solution to the polyoxyethylene polyoxypropylene ether segmented copolymer solution is 4: 1, centrifuging to remove supernatant, and determining the product to be natural polyphenol-pluronic gel consistent with the chemical structural formula through nuclear magnetism.
EXAMPLE 3 preparation of Natural Polyphenol-Pluronic gel
1) Dissolving tannic acid in double distilled water to form a tannic acid solution with the concentration of 50% (w/w);
2) dissolving polyoxyethylene polyoxypropylene ether block copolymer in double distilled water at 4 ℃ to form polyoxyethylene polyoxypropylene ether block copolymer solution with the concentration of 20% (w/w);
3) mixing and fully shaking the tannic acid solution and the polyoxyethylene polyoxypropylene ether segmented copolymer solution in the first step and the second step, wherein the volume ratio of the tannic acid solution to the polyoxyethylene polyoxypropylene ether segmented copolymer solution is 1: and 4, centrifuging to remove the supernatant to prepare the natural polyphenol-pluronic gel, and determining the product to be the natural polyphenol-pluronic gel consistent with the chemical structural formula through nuclear magnetism.
Taking example 1 as an example, the product can be determined to be natural polyphenol-pluronic gel consistent with the chemical structural formula through nuclear magnetism.
Meanwhile, as shown in FIG. 2, the TA-PF127 gel is subjected to Fourier transform infrared spectroscopy characterization, and the carbonyl peak of TA in the gel can be found to be 1714cm-1Changed to 1730cm-1And the peak value of PF127 carbon-hydrogen bond stretching is 2892cm-1Change to 2919cm-1Thus, it was confirmed that hydrogen bonding between TA and PF127 did occur in the gel product.
Effect example 1 measurement of dynamic viscosity of TA-PF127 gel
The vibration shearing experiment is carried out by a Rheometer, the Rheometer adopted in the experiment is a Discovery Hibridge Rheometer-3 model Rheometer of TA Instruments, fibrin glue is taken as a comparative example, and the experimental steps are as follows:
the TA-PF127 gel and the fibrin glue were placed on a 40mm test plate of an instrument for testing, respectively, and were blocked with silicone oil to prevent evaporation, and were measured at 37 degrees Celsius under a 0.1% tension environment with a variation of angular frequency ranging from 0.1 to 100 rad/s. The results are shown in FIG. 3, where G 'represents the elastic modulus, G' represents the loss modulus, η*Representing viscosity, G '/G' is less than 1 as the angular frequency is varied from 0.1 to 100rad/s, indicating that the gel is viscous, and as the frequency is increased, G 'and G' both increase, viscosity (. eta. eta.,. eta.*) The drop indicates that the gel has a high dynamic viscosity with good tissue adhesion potential.
Effect example 2 measurement of adhesive Strength and Water-sealing Property of TA-PF127 gel
The test of tissue adhesive strength and water sealing performance is carried out in vitro by adopting the pig dura mater tissue, and the test steps are as follows by taking fibrin glue as a comparative example:
tissue adhesion strength: the porcine dura was sliced to 1X 3cm2, 200. mu.l of TA-PF127 gel or fibrin glue was placed on one end of the slice, one end of the other dura was overlaid with it, the contact area was about 1X 1cm2, a pressure of 50g/cm2 was applied to the contact surface for 30 seconds, and then left to stand for 3 minutes. The minimum pull force that will separate the bonded sections is then measured with a spring tensioner and is defined as the tissue bond strength. And (3) water seal performance detection: the dura mater of swine was trimmed to a circular film, assembled on a test apparatus, and then a needle hole was punched in the film, which was covered with 100. mu.l of TA-PF127 gel or Fibrin glue, respectively, and after 3 minutes, the water pressure was gradually increased, and then the minimum water pressure at which liquid leakage occurred on the surface of the film was recorded as water-sealing property, and the results are shown in FIG. 4.
Testing the water seal performance: the porcine dura mater is trimmed into a circular film, the circular film is assembled on a water seal performance testing device, then a needle hole is punched on the film and is respectively covered by 100 mu l of TA-PF127 gel or fibrin glue, after 3 minutes, the water pressure is gradually increased, then the minimum water pressure which can cause the liquid leakage on the surface of the film is recorded and defined as water seal performance, the structure of the water seal performance testing device is shown in figure 5, and the testing result is shown in figure 6. Effect example 3 Performance test of TA-PF127 gel on cerebrospinal fluid leakage in the repair of rabbit dural injury model
Preparing a rabbit dura mater injury model, wherein the preparation process is common knowledge of technical personnel in the field, and the preparation process is not described herein, the repair effect of TA-PF127 gel in the application of the model is analyzed by a simple suture model of the rabbit dura mater injury model and a fascia transplantation model of the rabbit dura mater injury model respectively, the simple suture model of the rabbit dura mater injury model and the fascia transplantation model of the rabbit dura mater injury model are subjected to grouping setting experiment groups and reference groups for comparison test, wherein the simple suture model of the rabbit dura mater injury model is divided into the following groups: the method comprises the following steps of (1) simply sewing, covering TA-PF127 gel after sewing, and covering fibrin glue after sewing; grouping fascia transplantation models of rabbit dura mater injury models: simple fascia transplantation, TA-PF127 gel covering after fascia transplantation, and fibrin glue covering after fascia transplantation.
Performing cerebrospinal fluid leakage pressure test on the pure suture model group of the rabbit dura mater injury model and the fascia transplantation model group of the rabbit dura mater injury model, wherein the test method comprises the following steps: the method comprises the steps of placing a tube in a cerebellum medullary oblongata pool of a rabbit dura mater injury model, detecting intracranial pressure, recording the intracranial pressure as ICP, gradually increasing the intracranial pressure after dura mater injury and repair are completed, recording the minimum ICP capable of causing dura mater surface cerebrospinal fluid leakage as cerebrospinal fluid leakage pressure, and increasing the maximum pressure of the ICP to be 60cmH2O for preventing cerebral hernia.
As a result, as shown in FIGS. 7-8, it was found that TA-PF127 closures were able to significantly withstand greater cerebrospinal fluid pressure without cerebrospinal fluid leakage than fibrin glue closures and no material closures. Observation of tissue healing after fascia implantation by tissue section results are shown in fig. 9, and it can be found that TA-PF127 occlusion effectively promotes tissue attachment and healing of the implanted fascia and the local dura.
Effect example 4 verification of the Effect of TA-PF127 gel on scavenging oxygen free radicals in rat spinal cord injury model repair applications
The rat spinal cord injury model is prepared by a process well known to those skilled in the art, and the rat spinal cord injury model repair model is divided into two groups, which are not described herein in a relevant part: the rat spinal cord injury model is treated by covering TA-PF127 gel, and the rat spinal cord injury model is treated by covering fibrin glue; an experimental control group was additionally set: the rat spinal cord injury model was not treated for repair and is shown in the figure as SCI. By detecting the content of superoxide dismutase (SOD) and Malondialdehyde (MDA) related to oxygen free radicals in spinal cord tissues, the SOD and MDA detection kit used in the detection is provided for Nanjing to build a bioengineering research institute, the result is shown in figure 10, and the result shows that after spinal cord injury, the content of the MDA in local spinal cord tissues can be obviously reduced and the content of the SOD can be increased by locally using TA-PF127 gel within 1 week, so that the scavenging efficiency of the SOD on the local oxygen free radicals is reflected. After acute spinal cord injury, local oxygen free radical elevation is an important cause of secondary nerve injury, and therefore reducing oxygen free radicals is an effective means of controlling secondary nerve injury conditions.
Effect example 5 verification of the protective Effect of TA-PF127 gel on nerve tissue and recovery of nerve function after spinal cord injury
The hindlimb motor function and the bladder independent urination function of the rats of the experimental group and the control group are evaluated by the evaluation method of Basso, Beattie and Bresnahan, wherein the motor function is evaluated in 21 grades of 0 (complete paralysis) to 21 (normal). Hind limb motor function was evaluated weekly within 6 weeks after surgery, and functional recovery was observed starting 7 days after spinal cord injury in the rat spinal cord injury model, with a significant functional recovery effect (p < 0.05) compared to the control group observed after 6 weeks. The urinary bladder voluntary urination function is evaluated by a Liebscher scoring method, the result is shown in fig. 11(a and b), the hindlimb motor function of a rat spinal cord injury model after TA-PF127 gel treatment is better and faster in obvious recovery, in addition, the observation of spinal cord histology 5 weeks after injury shows that gel treatment can enable spinal cord tissues to maintain better integrity after injury, the result is shown in fig. 11(c), more neuron cells are kept to survive, the result is shown in fig. 11(d), and the experimental result shows that TA-PF127 gel has obvious protective effect and recovery effect of nerve function on the nerve tissues after spinal cord injury relative to fibrin glue.
The hydrophobic bond between the polyoxypropylene chains in the PF127 structure enables the TA-PF127 gel to have good waterproof performance, and the data of the TA-PF127 gel proves that the TA-PF127 gel has excellent viscosity and tissue adhesion capability, and can play a good role as a covering, a plugging object and an anastomosis adhesive on other tissues due to good cell compatibility, such as the TA-PF127 gel can play a role in vascular intervention plugging and tissue wound hemostasis.
The fibrin glue is medical fibrin glue, the medical fibrin glue is mature medical material, the medical performance of the fibrin glue is kept at an average level in a formal factory, so that batch difference does not exist, the animal model in the effect examples 3-5 monitors the basic body temperature in the test process, the contrast group and the experimental group do not have difference, the toxic and side effects of TA-PF127 gel on the animal model are proved to be small, and TA and PF127 are FDA approved safe compounds, the toxic and side effects on a human body are known, and the safety performance is high.
The above is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above-mentioned embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.

Claims (4)

1.一种天然多酚-普兰尼克凝胶,其特征在于:由单宁酸和聚氧乙烯聚氧丙烯醚嵌段共聚物共聚形成共聚物,其化学结构式为:1. a natural polyphenol-Pluronic gel, is characterized in that: by tannic acid and polyoxyethylene polyoxypropylene ether block copolymer copolymerization to form multipolymer, and its chemical structural formula is:
Figure DEST_PATH_IMAGE001
Figure DEST_PATH_IMAGE001
所述聚氧乙烯聚氧丙烯醚嵌段共聚物的数均分子量为1000~20000 Da。The number average molecular weight of the polyoxyethylene polyoxypropylene ether block copolymer is 1000-20000 Da.
2.根据权利要求1所述的一种天然多酚-普兰尼克凝胶,其特征在于:所述单宁酸和聚氧乙烯聚氧丙烯醚嵌段共聚物的摩尔比为33.2:1。2. a kind of natural polyphenol-Pluronic gel according to claim 1, is characterized in that: the mol ratio of described tannic acid and polyoxyethylene polyoxypropylene ether block copolymer is 33.2:1. 3.根据权利要求1所述的一种天然多酚-普兰尼克凝胶,其特征在于:所述单宁酸的数均分子量为500~5000 Da。3 . The natural polyphenol-pluronic gel according to claim 1 , wherein the number-average molecular weight of the tannic acid is 500-5000 Da. 4 . 4.根据权利要求1所述的一种天然多酚-普兰尼克凝胶的制备方法,其特征在于:包括以下步骤,4. the preparation method of a kind of natural polyphenol-Pluronic gel according to claim 1, is characterized in that: comprise the following steps, 步骤一、将单宁酸溶于双蒸水中,形成浓度为50%(w/w)单宁酸溶液;Step 1. Dissolving tannic acid in double distilled water to form a tannic acid solution with a concentration of 50% (w/w); 步骤二、将聚氧乙烯聚氧丙烯醚嵌段共聚物溶于0-8摄氏度的双蒸水中,形成浓度为20%(w/w)聚氧乙烯聚氧丙烯醚嵌段共聚物溶液;Step 2, dissolving the polyoxyethylene polyoxypropylene ether block copolymer in double distilled water at 0-8 degrees Celsius to form a polyoxyethylene polyoxypropylene ether block copolymer solution with a concentration of 20% (w/w); 步骤三、将步骤一和步骤二中的单宁酸溶液和聚氧乙烯聚氧丙烯醚嵌段共聚物溶液混合震荡充分,两者体积比为1:0.25-4,然后离心去除上清,制备的到天然多酚-普兰尼克凝胶。Step 3. Mix and shake the tannic acid solution and the polyoxyethylene polyoxypropylene ether block copolymer solution in the first and second steps, and the volume ratio of the two is 1:0.25-4, and then centrifuge to remove the supernatant to prepare to natural polyphenols - Pluronic Gel.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014126537A1 (en) * 2013-02-13 2014-08-21 Agency For Science, Technology And Research A Polymeric System for Release of an Active Agent
CN108721250A (en) * 2018-07-05 2018-11-02 华东师范大学 A kind of boric acid class Nano medication compound of bio-compatible and its preparation method and application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014126537A1 (en) * 2013-02-13 2014-08-21 Agency For Science, Technology And Research A Polymeric System for Release of an Active Agent
CN108721250A (en) * 2018-07-05 2018-11-02 华东师范大学 A kind of boric acid class Nano medication compound of bio-compatible and its preparation method and application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Polyphenol-Poloxamer Self-Assembled Supramolecular Nanoparticles for Tumor NIRF/PET Imaging;Xinyu Wang等;《Adv. Healthcare Mater》;20180514;第7卷;摘要、文章第1页右栏第1段至第2页右栏末段、第5页右栏末段至第6页右栏第1段 *

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