CN109847111B - Anti-adhesion material containing bletilla striata polysaccharide and preparation method thereof - Google Patents
Anti-adhesion material containing bletilla striata polysaccharide and preparation method thereof Download PDFInfo
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Abstract
The invention relates to an anti-adhesion material containing bletilla striata polysaccharide and a preparation method thereof. The anti-adhesion material is prepared by adding BDDE into a mixed solution of bletilla striata polysaccharide and hydroxyalkyl cellulose under an alkaline condition to form an absorbable anti-adhesion material, and can be prepared into anti-adhesion sponges, anti-adhesion membranes and anti-adhesion gels through different process conditions. The compound prepared by the chemical reaction of the bletilla polysaccharide, the hydroxyalkyl cellulose and the BDDE can be used for preventing adhesion of pelvic cavities, abdominal cavities and the like, has the functions of stopping bleeding and promoting healing, has excellent biological safety, and is strong in operation convenience and good in clinical application prospect.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a degradable anti-adhesion material which directly acts on bloody wounds of people, mammals and the like and has the functions of stopping bleeding and promoting wound healing and a preparation method thereof.
Background
Tissue adhesion is likely to occur after surgical operations. Adhesions are abnormal structures formed by the connective tissue fiber band joining adjacent tissues or organs, and can range from a thin film to dense, vascular scar tissue. Postoperative adhesions are both a common clinical phenomenon in the surgical field and a necessary pathophysiological process in the postoperative healing process. According to statistics, the incidence rate of postoperative adhesion reaches more than 90%. Among them, 10% of adhesions cause a series of complications to patients, resulting in problems of the patients' quality of life being reduced or even life-threatening. Causes of adhesions include surgical trauma, ischemia, the presence of foreign bodies, bleeding and exposure of the wound surface and bacterial infection. The prevention of postoperative adhesion is one of the difficulties of surgical operation and is a research target of medicine for hundreds of years. Adhesions are a common phenomenon after abdominal, hand and cardio-thoracic surgical procedures. Peritoneal adhesions are a common complication of abdominal and pelvic surgeries, with an incidence of 67-93% in abdominal surgeries and 97% in gynecological pelvic surgeries. Its complications include intestinal obstruction, difficulty in reoperation, chronic abdominal pelvic pain, and female infertility. The key to the formation of peritoneal adhesions is 5-7 days after the last day. If a spacer is placed between the damaged surfaces of the peritoneum and kept for more than one week, the damaged peritoneum can be epithelialized and finally healed without adhesion.
Rhizoma bletillae (rhizoma bletillae) is a dried tuber of rhizoma bletillae of Orchidaceae, which is a Chinese medicament with long-term administration history, is bitter, astringent, sweet and slightly cold in nature, enters lung, liver and stomach channels, and has the effects of astringing, stopping bleeding, clearing heat and dampness, relieving swelling and promoting granulation. Rhizoma bletillae extract is also used in experiments, can quickly form artificial thrombus, is commonly used for trauma hemostasis, and has good effect on visceral hemorrhage. The bletilla striata has obvious effect of promoting keratinocytes, has important influence on treating skin wounds, stopping bleeding and early healing, further indicates that bletilla striata gum directly participates in the repair and metabolic processes of damaged tissues or cells, and has obvious curative effect.
Blood exuded from the wound surface after debridement is also a substance causing adhesion formation. In the united states, only three products have been FDA approved for reducing post-operative adhesion formation.
The first approved anti-adhesion product is an interceded anti-adhesion membrane of Qiangsheng company, belongs to a sterile braided fabric prepared by the controllable oxidation of regenerated hydroxyalkyl cellulose, is used for preventing and treating the postoperative adhesion of open gynecological pelvic surgery (or caesarean section operation), and can form a gel-like protective layer on the surface layer of a wound after being placed for 8 hours to fill the gaps among fibers.
The second is Seprafilm anti-adhesion membrane of silofil group, which is a chemically modified membrane (with prolonged in vivo retention time) composed of sodium hyaluronate and carboxymethyl hydroxyalkyl cellulose, and is relatively fragile. The Seprafilm anti-adhesion membrane is suitable for preventing and treating adhesion formation after an open surgery, and can reduce the incidence, range and severity of postoperative adhesion between an abdominal wall and organs (such as omentum majus, small intestine, bladder, stomach and the like) and between a uterus and surrounding tissues (such as an oviduct, ovary, large intestine and bladder). In one study, patients with hysteromyoma with open surgery were divided into two groups. Anti-adhesion membranes are placed on the front and back surfaces of the uterus; the other group was not placed. And carrying out secondary detection on the laparoscope in an early stage and evaluating the effect of the anti-adhesion membrane. As a result, the situation of uterine adhesion is reduced by 36.8% compared with the situation of uterine adhesion by using an anti-adhesion membrane group. In the study of colectomy, it was also found that the severity of the adhesions was significantly reduced after the use of an anti-adhesion membrane. This advantage exists but is not apparent in general surgery. And no difference was found in gynecological surgery.
The third one is Adept icodextrin solution of Baxter company, which is an anti-adhesion liquid used in abdominal cavity, and is mainly suitable for preventing the generation of postoperative adhesion of gynecological laparoscopic adhesion decomposition. The incidence of blocking was found to decrease by 9.8% with icodextrin solution. The 24 sites evaluated by the institute generally reduced adhesion, rather than a single site alone. However, follow-up studies on randomized controlled trials of another 400 patients found that the effect of icodextrin solutions in reducing post-operative adhesion formation was not statistically significant. All three products function as a physical barrier, act as a barrier, and are eventually either degraded or absorbed and do not remain in the abdominal cavity. Therefore, they all play a role in physical barrier separation during the peritoneal repair period and play a role in adhesion prevention.
The current medical anti-adhesion materials in China comprise sodium hyaluronate postoperative anti-adhesion liquid flowable substances which are influenced by the body position change of patients. Is suitable for surgical operations such as joint operation, ophthalmic operation and the like, improves the space of the ophthalmic operation, and has the functions of lubricating and buffering the joint. The polylactic acid anti-adhesion membrane has low strength and poor flexibility, and needs cutting and sewing needle fixing when in use. Is suitable for surgical operations of orthopedics, neurosurgery, abdominal cavity, pelvic cavity and the like. The medical chitosan film is used for preventing adhesion, liquid easily flowing substances are influenced by the body position change of a patient, the medical chitosan film has a lubricating effect, and the retention time of the activity of the material is short. Is suitable for clinical operations of general surgery, hepatobiliary surgery, tumor surgery, obstetrics and gynecology, and the like. The anti-adhesion material is urgently required to be used in various surgeries so as to reduce the surgical risk and reduce postoperative complications. The basic and clinical research of the anti-adhesion material has a profound significance for solving the problem of life-long residual waste and even life danger of patients caused by adhesion generally existing in surgical operations. It is therefore desirable to provide a release agent for preventing adhesion formation that has good biocompatibility, self-adhesion, degradability and absorbability, sufficient in vivo residence time, promotes wound healing, and minimizes fibrous tissue proliferation.
Disclosure of Invention
The invention aims to provide a novel material for preventing adhesion after surgery, which has good biocompatibility, automatic adhesion, degradability and absorbability, sufficient in-vivo retention time, promotes wound healing, is beneficial to use of patients and promotes recovery of the patients. The research of the invention finds that the anti-adhesion material prepared by taking bletilla polysaccharide, hydroxyalkyl cellulose and BDDE (1, 4-butanediol diglycidyl ether) as raw materials can effectively prevent tissue adhesion after operation, stop bleeding and promote wound healing, and belongs to degradable biomedical materials. Thus, the present invention has been made.
Specifically, the invention provides an anti-adhesion material containing bletilla striata polysaccharide, which is prepared from raw materials including bletilla striata polysaccharide, hydroxyalkyl cellulose, BDDE and the like.
Further, the hydroxyalkyl cellulose is preferably selected from one or more of hydroxymethyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose.
Furthermore, the molecular weight of the bletilla polysaccharide is 12000-320000 Da.
Further, the bletilla striata polysaccharide is prepared according to the method of Chinese patent application CN 201810386516.2.
The bletilla polysaccharide of the present invention may be commercially available or prepared according to conventional methods in the art.
Further, the anti-adhesion material containing the bletilla striata polysaccharide is prepared from the following raw materials in parts by weight: 5-100 parts of bletilla polysaccharide, 5-100 parts of hydroxyalkyl cellulose and 0.01-5 parts of BDDE.
Preferably, the anti-adhesion material containing the bletilla striata polysaccharide is prepared from the following raw materials in parts by weight: 30-100 parts of bletilla polysaccharide, 10-50 parts of hydroxyalkyl cellulose and 0.05-3 parts of BDDE.
Further preferably, the anti-adhesion material containing the bletilla striata polysaccharide is prepared from the following raw materials in parts by weight: 50-80 parts of bletilla polysaccharide, 20-30 parts of hydroxyalkyl cellulose and 0.05-2 parts of BDDE.
Specifically, the anti-adhesion material containing the bletilla striata polysaccharide is a novel material formed by crosslinking the bletilla striata polysaccharide, hydroxyalkyl cellulose and BDDE through chemical reaction. The gel can be made into different forms according to actual needs, such as gel, film, sponge and the like.
Further, the thickness of the anti-blocking material is 0.01-2 mm.
The invention also provides a preparation method of the anti-adhesion material, which comprises the following steps: preparing rhizoma bletilla polysaccharide and hydroxyalkyl cellulose into water solution respectively; then mixing the rhizoma bletillae polysaccharide solution and the hydroxyalkyl cellulose solution, adjusting the pH to 10.5-12, adding BDDE, and stirring uniformly to prepare a mixed solution; further preparing the anti-adhesion material.
Preferably, deionized water is used to prepare the bletilla polysaccharide solution and the hydroxyalkyl cellulose solution.
The pH is preferably adjusted with sodium hydroxide.
Generally, stirring is required for 10-120min until the system is homogeneous.
Preferably, the concentration of the bletilla striata polysaccharide solution is 0.5-30% (w/w); and/or the concentration of the hydroxyalkyl cellulose solution is 0.5-30% (w/w).
In the preparation method, the mixed solution can be prepared into different forms according to actual requirements, for example, products in the forms of anti-adhesion gel, anti-adhesion membrane, anti-adhesion sponge and the like are prepared by adopting methods such as in-situ gelling, casting film forming, freeze drying and the like, so that the preparation method is suitable for different anti-adhesion requirements of operations, is convenient for operation, and is suitable for industrial production.
Specifically, the mixed solution can be stood (preferably, stood at 4-60 ℃ for 0.1-50h) to prepare anti-adhesion gel; or filtering the mixed solution (preferably 200-400 mesh sieve), performing vacuum defoaming, standing at normal temperature, and casting to form an anti-adhesion membrane; or coagulating the mixed solution at-10 deg.C to-50 deg.C to obtain solid, and vacuum drying (preferably vacuum degree of 1-10 pascal) to obtain anti-adhesion sponge. The anti-adhesion sponge is of a porous structure, and the pore diameter is preferably 1-100 μm.
In order to ensure the safety of the direct use of the anti-adhesion material on the bloody wound surface, the anti-adhesion material can be further sterilized after being packaged, wherein the sterilization modes include but are not limited to ethylene oxide sterilization, Co-60 radiation sterilization, gamma radiation sterilization and ozone sterilization.
On the basis of the common knowledge in the field, the above-mentioned preferred conditions can be combined with each other to obtain the preferred embodiments of the present invention.
The raw materials or reagents involved in the present invention are commercially available.
The invention achieves the following technical effects:
1) the anti-adhesion material is prepared from bioabsorbable macromolecules, has good biocompatibility, can be decomposed and absorbed by organisms, does not remain foreign bodies, and can effectively prevent tissue adhesion after an operation.
2) The anti-adhesion material comprises raw materials of bletilla polysaccharide, hydroxyalkyl cellulose and BDDE. The bletilla polysaccharide is a safe and effective immune response regulator, an anti-angiogenesis medicine and a traditional simple TAC treatment. Has wide application space in the aspects of treating ulcerative colitis, stopping bleeding in operation, acute upper gastrointestinal tract hemorrhage, promoting wound skin healing and the like. Gelatin and bletilla hyacinthine gum are used as support materials to compound the traditional Chinese medicine extract into the support materials, and a spongy porous material is prepared by a freeze-drying method, has uniformly distributed gaps and is mutually communicated, is used for culturing mouse fibroblasts, and can enable the cells to be better adhered and grow. The rhizoma bletillae polysaccharide can enhance the activity of a third factor of blood platelets, remarkably shorten the blood coagulation time and the prothrombin formation time, inhibit the activity of plasmin, has the hemostatic effect on local bleeding, and has good external hemostatic effect on bleeding of parenchymal organs (liver and spleen) and muscle blood vessels and the like. As a natural polymer material, the bletilla striata polysaccharide biological dressing material has the advantages of function slow release, local detention, self degradability, no stimulation and no toxic or side effect, and is a biological dressing material with great development prospect, so the bletilla striata polysaccharide is more and more emphasized in the medicinal preparation process due to good biocompatibility and degradability. BDDE can play a role in bridging among linear molecules so as to enable a plurality of linear molecules to be bonded and crosslinked into a substance with a network structure, and the BDDE can promote or regulate the formation of covalent bonds and ionic bonds among polymer molecular chains, and is a commonly used crosslinking agent. The hydroxyalkyl cellulose belongs to nonionic soluble hydroxyalkyl cellulose ether, and hydroxyl on cellulose fiber molecules can react with a plurality of chemical groups so as to generate the anti-adhesion medical isolating material which can absorb water and swell to form mechanical isolation function in vivo and further dissolve. The water-soluble cellulose is dissolved to form gel, and is placed between tissues of different wound surfaces, so that the gel can coat organs and tissues, effectively plays a role in isolation and lubrication, effectively prevents adhesion formation, does not influence wound surface healing and organisms, is absorbed by or discharged out of a human body after being retained for a certain time, and is convenient for surgical operation. The isolating material is kept in the body for a certain time to play a role of mechanical isolation. Reduce fibrin exudation and deposition, and prevent adhesion formation during epithelial regeneration. Prevent the inflammatory cells and other cells from moving during the peritoneal repair, form a protective film on the serosa and keep for a long time, so that the serosa defect is better recovered, and the anti-adhesion purpose is achieved.
The substances have good biocompatibility, can effectively prevent tissue adhesion after operation, and the prepared biomaterial has good biocompatibility and mechanical property.
The invention can be used for preventing pelvic cavity, abdominal cavity and other parts from adhesion, can also be used for bloody wounds of human beings, mammals and the like, has the functions of stopping bleeding and promoting healing, has excellent biological safety, and has strong operation convenience and good clinical application prospect.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. The operations referred to in the examples are, unless otherwise specified, all those of ordinary skill in the art. This example illustrates the technical effects of the technical solution of the present invention as a film agent.
The following examples and comparative examples, with the exception of specific indications, and the polysaccharides having molecular weights of 12000-320000 Da, were prepared according to the method of Chinese patent application CN 201810386516.2.
Example 1
The anti-adhesion material containing the bletilla polysaccharide is a biological membrane prepared from 60 parts by weight of the bletilla polysaccharide, 60 parts by weight of hydroxypropyl cellulose and 0.6 part by weight of BDDE.
The preparation method comprises the following steps: dissolving rhizoma bletilla polysaccharide and hydroxypropyl cellulose in deionized water respectively to obtain rhizoma bletilla polysaccharide solution with concentration of 0.5% (w/w) and hydroxypropyl cellulose solution with concentration of 0.5% (w/w); mixing the two solutions uniformly, and adjusting the pH value to 10.5 with sodium hydroxide; adding BDDE according to the proportion, and stirring uniformly (at least stirring for 10-30min) to prepare a mixed solution; sieving with 300 mesh sieve, vacuum defoaming, standing at normal temperature, and casting to form film.
Example 2
The anti-adhesion material containing the bletilla striata polysaccharide is a biological membrane prepared from 30 parts by weight of the bletilla striata polysaccharide, 20 parts by weight of hydroxyethyl cellulose and 2 parts by weight of BDDE.
The preparation method differs from example 1 only in that: the concentration of the prepared bletilla striata polysaccharide solution is 2% (w/w), the concentration of the hydroxyethyl cellulose solution is 1.25% (w/w), and the pH value is 10.8.
Example 3
The anti-adhesion material containing the bletilla striata polysaccharide is a biological membrane prepared from 30 parts by weight of the bletilla striata polysaccharide, 20 parts by weight of hydroxymethyl cellulose and 2 parts by weight of BDDE.
The preparation method differs from example 1 only in that: the prepared rhizoma bletillae polysaccharide solution has the concentration of 5% (w/w), the hydroxymethyl cellulose solution has the concentration of 2.9% (w/w) and the pH value is 11.0.
Example 4
The anti-adhesion material containing the bletilla polysaccharide is a biological membrane prepared from 50 parts by weight of the bletilla polysaccharide, 30 parts by weight of hydroxyethyl cellulose and 3 parts by weight of BDDE.
The preparation method differs from example 1 only in that: the prepared rhizoma bletillae polysaccharide solution has the concentration of 10% (w/w), the hydroxyethyl cellulose solution has the concentration of 5% (w/w) and the pH value is 11.2.
Example 5
The anti-adhesion material containing the bletilla striata polysaccharide is a biological membrane prepared from 40 parts by weight of the bletilla striata polysaccharide, 25 parts by weight of hydroxymethyl cellulose and 2.5 parts by weight of BDDE.
The preparation method differs from example 1 only in that: the prepared rhizoma bletillae polysaccharide solution has the concentration of 15% (w/w), the hydroxymethyl cellulose solution has the concentration of 10% (w/w) and the pH value is 11.5.
Example 6
The anti-adhesion material containing the bletilla polysaccharide is a biological membrane prepared from 100 parts by weight of the bletilla polysaccharide, 80 parts by weight of hydroxypropyl cellulose and 10 parts by weight of BDDE.
The preparation method differs from example 1 only in that: the prepared rhizoma bletillae polysaccharide solution has the concentration of 20% (w/w), the hydroxypropyl cellulose solution has the concentration of 20% (w/w) and the pH value is 12.
Comparative example 1
The difference between the comparative example and the example 3 is only that the raw material components are different, and the anti-adhesion material of the comparative example is a biological membrane prepared by 30 parts by weight of bletilla striata polysaccharide, namely the raw materials do not comprise hydroxymethyl cellulose and BDDE.
Comparative example 2
The difference between the comparative example and the example 3 is only that the raw material components are different, and the anti-adhesion material of the comparative example is a biological membrane prepared by 30 parts by weight of bletilla polysaccharide and 2 parts by weight of BDDE, namely the raw material does not contain hydroxymethyl cellulose.
Comparative example 3
The difference between the comparative example and the example 3 is only that the raw material components are different, and the anti-adhesion material of the comparative example is a biological membrane prepared by 20 parts by weight of hydroxymethyl cellulose and 2 parts by weight of BDDE, namely the raw material does not contain bletilla striata polysaccharide.
Comparative example 4
The difference between the comparative example and the example 3 is only that the molecular weight of the raw materials of the bletilla striata polysaccharide is different, and the comparative example is a biological membrane prepared from the bletilla striata polysaccharide with the molecular weight of 480000-630000 Da.
Experimental example 1
(I) test of effectiveness
80 adult healthy female SD rats are randomly and averagely divided into 5 groups, a model group, a positive control group and three test groups, wherein each group comprises 16 rats, and the abdominal adhesion prevention of the rats is contrasted and researched.
Test group A, B, C was each implanted with the anti-blocking materials prepared in examples 3, 4, and 6,
a positive control group is implanted with commercial Seprafilm (No. 2014 No. 3644089 of food and drug administration apparatus);
the experimental method comprises the following steps: cleaning rat, fasting for 12h before operation, performing intraperitoneal injection anesthesia with 3% sodium pentobarbital (35mg/Kg) 10min before operation, removing hair from abdomen, cleaning abdomen with sterile soap, sterilizing abdomen skin with medical alcohol, spreading sterile towel, making abdominal incision, extracting the last ileum, scratching with knife until slight macula hemorrhage appears, and making two intestinal serosa 1cm and left and right respectively2The abdominal implantation size of each rat in the test group and the positive control group is 2cm2The anti-adhesion material is sewed with the incision, wrapped by sterile dressing, applied on the skin suture part with erythromycin ointment after closing the abdomen, marked and then put into a cage for free breeding. The model groups were not implanted with any film. Rats were sacrificed at three time points of 7, 14, 21d, three rats per group were sacrificed at 7 and 21 days, and 10 rats per group were sacrificed at 14d, as observed by laparotomy.
And (3) adhesion evaluation: rats are anesthetized and killed 14 days after operation, the abdominal cavity is opened by a U-shaped incision, the rats are fully exposed, and the adhesion degree among the abdominal wall, the terminal ileum and the fat of the rats is scored. The scores were divided into 5 grades (see table 1).
TABLE 1 evaluation of blocking
| Scoring | Description of the Scoring |
| 0 | No adhesion |
| 1 | Fine film-like adhesions |
| 2 | Fine adhesion of more than one site |
| 3 | Coarse adhesion concentrated at one point |
| 4 | Large and large adhesion in plane |
Statistical analysis:
the statistics of experimental data are analyzed by using SPSS17.0 software, the adhesion scores of a model group, a positive control group and three test groups are compared by adopting one-factor variance analysis, the later multiple tests adopt Tukey HSD test, and the adhesion rate adopts chi test2Inspection, P<0.05 the difference was considered statistically significant
Table 2 evaluation of adhesion after abdominal surgery in rats
| Group of | Model set | Positive control group | Test group A | Test group B | Test group C |
| Number of animals | 10 | 10 | 10 | 10 | 10 |
| 0 | 0 | 8 | 9 | 9 | 8 |
| 1 | 0 | 1 | 0 | 1 | 1 |
| 2 | 0 | 0 | 1 | 0 | 1 |
| 3 | 0 | 1 | 0 | 0 | 0 |
| 4 | 10 | 0 | 0 | 0 | 0 |
| Number of adherent animals | 10 | 2 | 1 | 1 | 2 |
| Percentage of blocking | 100 | 20 | 10 | 10 | 20 |
| Adhesion scoring | 4.0 | 0.4 | 0.2 | 0.1 | 0.3 |
As a result, four groups of anti-adhesion products can prevent abdominal adhesion of rats, the test group has the best effect, the adhesion score and the adhesion rate are lower (0.1-0.3, 10-20%), the statistical significance is achieved compared with the model group (4.0, 100%) (P is less than 0.05), the adhesion score and the adhesion rate of the test group (0.1-0.3, 10-20%) are slightly lower than those of the positive control group (0.4, 20%), and the statistical significance is avoided compared with the positive control group (P is more than 0.05). The test data show that the tissue adhesion of the control group of mice which do not adopt the biomembrane for preventing the tissue adhesion after the operation is obvious, but the tissue adhesion of the test group is not obvious, so the anti-adhesion product has certain curative effect on preventing the terminal ileum and the abdominal wall of the rat.
(II) in vivo degradation test
The tissue adhesion condition of the rats in each group at the 7 th time point, the 14 th time point and the 21d time point is observed, and the rats in the model group are found to generate extensive adhesion which is difficult to separate.
At 7d, the membrane morphology of the Seprafilm in the positive control group had been completely lost and was invisible to the naked eye; the absorbable anti-adhesion membrane in the test group can still maintain a relatively complete membrane structure.
At 14d, the positive control group showed slight adhesion that could automatically separate due to the rapid degradation of the anti-adhesion membrane, and the absorbable anti-adhesion membrane in the test group was already in gel form and still maintained a certain barrier effect.
At 21d, the absorbable anti-adhesion membrane in the test group was completely degraded, and no adhesion was generated in both the test group and the positive control group. The absorbable anti-adhesion membrane has a remarkable anti-adhesion effect, has stronger in-vivo degradation resistance and can be maintained for a longer time compared with an anti-adhesion product Seprafilm.
Experimental example 2 measurement of expansion factor and breaking tension
The water absorption capacity and mechanical strength of the film were evaluated by measuring the expansion factor and breaking tension of the anti-blocking materials of examples 1 to 3 and Sepharam (same as in example 1), respectively.
Expansion factor: immersing an appropriate amount of absorbable anti-adhesion membrane in physiological saline until the membrane is saturated in water, and precisely weighing the membrane with the mass M2Then the film is placed in an oven to be dried to constant weight, and the film mass is precisely weighed as M1The expansion factor was calculated as follows: expansion factor of M2/M1。
Breaking tension: the maximum breaking tension of the absorbable anti-adhesion film is detected by a universal testing machine, the speed is 10mm/min, the distance between fixed ends is 2cm, and the width of the film is 1 cm.
TABLE 3 comparison of the Properties of the inventive Material
| Example 1 | Example 2 | Example 3 | Seprafilm | |
| Expansion factor | 24.5 | 22.6 | 17.6 | 32.5 |
| Breaking tension | 40.6 | 43.5 | 48.3 | 38.9 |
In the preparation process of the anti-adhesion material film, the smaller expansion ratio and the larger mechanical strength are more beneficial to increasing the flexibility of the film. As can be seen from Table 3, the anti-adhesion material prepared by the invention has smaller expansion times and larger maximum breaking force; the smaller the membrane deformation after meeting water, the higher the mechanical strength, and the more easily the complete membrane shape can be kept in the using process.
EXAMPLE 3 Whole blood coagulation test
The whole blood coagulation test was performed on each of the four anti-adhesion materials provided in example 3 and comparative examples 1 to 3.
10mg of the anti-adhesion material prepared in example 3 was weighed out and placed in a petri dish and cultured at 37 ℃ for 5min, then 200. mu.L of anticoagulated blood was slowly dropped onto the surface of the sample, followed by addition of 20. mu.L of 0.2mol/L calcium chloride solution and continued culture at 37 ℃ for 5 min. Thereafter, 10ml of distilled water was carefully added to the petri dish and cultured with shaking at 30rpm in a shaker for 10min while repeating the above procedure with comparative examples 1 to 3 as a control group, and the adsorption of the anti-adhesion sponge to erythrocytes was observed. The experimental result shows that compared with the comparative examples 1-3, the anti-adhesion material in the example 3 has better erythrocyte adsorption effect and stronger hemostatic effect.
Experimental example 4 gel time measurement experiment
The measurement of gel time was carried out for each of the anti-blocking materials provided in example 3 and comparative examples 1 to 3.
The anti-blocking material paste prepared in example 3 was examined for changes with time in the elastic modulus G 'and loss modulus G' by using a rotary cone rheometer (TA, DHR-1, USA) with the temperature set at 37 ℃, the diameter of the aluminum plate at 40mm, the gap of the sample at 25 μm, the frequency at 0.1 to 100rad/s, and the examination time at 600s, while repeating the above procedure with comparative examples 1 to 3 as a control group, and counting the time for gelling. Experimental results show that the glue forming time of the anti-adhesion material prepared in example 3 is less than 3 seconds, and the glue forming time of the anti-adhesion materials prepared in comparative examples 1-3 is more than 1min, which indicates that the anti-adhesion material has better convenience in operation.
Experimental example 5 wound healing test
Wound healing experiments were performed on the anti-adhesion materials provided in example 3 and comparative examples 1 to 3, respectively.
Anesthetizing and disinfecting an SD rat as an experimental animal, and then respectively taking wound surfaces with the diameter of about 4cm on two sides of a spine, wherein the experimental group is to inject the anti-adhesion material prepared in the embodiment 3 into the wound surfaces and then cover the wound surfaces with a disinfection dressing; the wounds of the control group were covered with only the disinfectant dressing, and the above procedure was repeated using comparative examples 1-3 as control groups to observe the healing effect. The results of 7 days after the operation showed that the SD rats using the anti-adhesion material of example 3 healed the wound surface on the back faster than those of comparative examples 1 to 3, and had an effect of promoting healing.
Experimental example 6 test of micropore structure of scanning electron microscope
And observing the cross section and the hole structure of the film by a scanning electron microscope, wherein the longitudinal section is brittle-broken in liquid nitrogen, and a scanning sample is subjected to metal spraying treatment at a scanning voltage of 21.0 kv. Scanning electron microscope results show that compared with the comparative example 4, the anti-adhesion material in the example 3 has a more regular membrane structure, more uniform pore diameter and good pore connectivity, and is beneficial to cell internal growth and transportation and discharge of nutrients and metabolites.
Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. An anti-adhesion material containing bletilla striata polysaccharide is characterized by being prepared by crosslinking 5-100 parts by weight of bletilla striata polysaccharide, 5-100 parts by weight of hydroxyalkyl cellulose and 0.01-5 parts by weight of BDDE through chemical reaction; the molecular weight of the bletilla polysaccharide is 12000-320000 Da.
2. The adhesion-preventing material according to claim 1, which is an adhesion-preventing gel, an adhesion-preventing film or an adhesion-preventing sponge.
3. The adhesion-preventing material according to claim 2, wherein the adhesion-preventing sponge has a porous structure and a pore size of 1 to 100 μm.
4. Anti-blocking material according to any of claims 1 to 3, characterized in that the hydroxyalkyl cellulose is selected from one or more of hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose.
5. The adhesion-preventing material according to any one of claims 1 to 3, which is prepared from the following raw materials in parts by weight: 30-100 parts of bletilla polysaccharide, 10-50 parts of hydroxyalkyl cellulose and 0.05-3 parts of BDDE.
6. The adhesion-preventing material according to any one of claims 1 to 3, which is prepared from the following raw materials in parts by weight: 50-80 parts of bletilla polysaccharide, 20-30 parts of hydroxyalkyl cellulose and 0.05-2 parts of BDDE.
7. The adhesion-preventing material according to any one of claims 1 to 3, wherein the thickness of the adhesion-preventing material is 0.01 to 2 mm.
8. The process for producing the adhesion-preventing material according to any one of claims 1 to 7, which comprises: preparing rhizoma bletilla polysaccharide and hydroxyalkyl cellulose into water solution respectively; then mixing the rhizoma bletillae polysaccharide solution and the hydroxyalkyl cellulose solution, and adjusting the pH to 10.5-12; adding BDDE, and stirring uniformly to prepare a mixed solution; further preparing the anti-adhesion material.
9. The method according to claim 8, wherein the concentration of the solution of bletilla striata polysaccharide is 0.5-30% (w/w); and/or the concentration of the hydroxyalkyl cellulose solution is 0.5-30% (w/w).
10. The production method according to claim 8 or 9, characterized by further comprising: standing the mixed solution to prepare anti-adhesion gel; or filtering the mixed solution, defoaming under reduced pressure, standing at normal temperature, and casting to obtain an anti-adhesion membrane; or coagulating the mixed solution into solid at-10 deg.C to-50 deg.C, and vacuum drying to obtain the final product.
Priority Applications (1)
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