CNF-C / PVA composite hydrogel, cervical support as well as preparation and application of CNF-C / PVA composite hydrogel and cervical support

Abstract

The invention relates to CNF-C / PVA composite hydrogel, a cervical support as well as preparation and application of the CNF-C / PVA composite hydrogel and the cervical support, the composite hydrogel is prepared from raw materials containing carboxylated nanocellulose fibers CNF-C and polyvinyl alcohol PVA through freezing and thawing cycle treatment, and the carboxyl content in the carboxylated nanocellulose fibers CNF-C is 1.7-2.5 mmol / g; the alcoholysis degree of the polyvinyl alcohol PVA is more than 98 mol%, and the polymerization degree of the polyvinyl alcohol PVA is 2200-2500. The cervical support comprises a main body part and a cavity, and the main body part is composed of CNF-C / PVA composite hydrogel. According to the invention, through a nanocellulose fiber compounding and dynamic cross-linking strategy, the mechanical property of the composite material is regulated and controlled, so that the composite material is dynamically matched with the cervical tissue of a human body, reliable supporting force can be provided, and mechanical damage to mucous membranes can be reduced.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of medical devices, and particularly relates to a CNF-C / PVA composite hydrogel, a cervical support and preparation and application thereof. BACKGROUND

[0002] Cervical prolapse is a common symptom of female pelvic floor dysfunction, and the cervical support is initially a medical device for gynecological treatment of female pelvic organ prolapse. In recent years, the cervical support has gradually been concerned as a new intervention measure for preventing premature birth. Compared with other intervention measures for preventing premature birth commonly used in the clinic, the cervical support has the advantages of non-invasiveness, easy taking and placing, simple operation, safety and small pain of patients.

[0003] The cervical support (such as a silicone cervical support) used at the present stage has high material hardness and strong foreign body sensation, which leads to inflammatory reactions, increased secretions and reduced comfort of patients during use. Clinical studies show that an ideal cervical support needs to meet a support force of >100 N and high dynamic fitting with cervical tissue, which poses double challenges to the mechanical properties and biocompatibility of the material.

[0004] Polyvinyl alcohol (PVA) hydrogel is regarded as an ideal alternative material due to its excellent non-toxicity, biodegradability, hydrophilicity, water solubility and chemical stability, but traditional homogeneous PVA hydrogel has problems of insufficient mechanical strength and poor fatigue resistance, and especially cannot meet the needs of supporting medical devices. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a CNF-C / PVA composite hydrogel, a cervical support and preparation and application thereof, which overcome the technical problem that the mechanical properties and comfort of traditional materials are difficult to be considered simultaneously.

[0006] The present application provides a CNF-C / PVA composite hydrogel, which is obtained by freeze-thaw cycles with raw materials containing carboxylated nanocellulose fibers (CNF-C) and polyvinyl alcohol (PVA);

[0007] The carboxyl content in the carboxylated nanocellulose fibers (CNF-C) is 1.7-2.5 mmol / g; the alcoholysis degree of the polyvinyl alcohol (PVA) is more than 98 mol%, and the polymerization degree is 2200-2500.

[0008] The raw materials also contain an antibacterial agent.

[0009] The present application provides a preparation method of any CNF-C / PVA composite hydrogel, which comprises:

[0010] Carboxylated nanocellulose fibers (CNF-C), polyvinyl alcohol (PVA) and water are mixed, stirred, defoamed, and then subjected to freeze-thaw cycle treatment to obtain a CNF-C / PVA composite hydrogel.

[0011] Preferably, an antibacterial agent can be added moderately in the preparation method.

[0012] Preferably, the mass ratio of polyvinyl alcohol (PVA) to carboxylated nanocellulose fibers (CNF-C) is 1:0.1 to 1:0.25.

[0013] Preferably, the stirring is carried out at 25-100℃ for 10-30min, and the further stirring temperature is 80-100℃.

[0014] Preferably, the defoaming is ultrasonic defoaming, wherein the ultrasonic temperature is 55-65℃ and the time is 10-25min.

[0015] Preferably, the freeze-thaw cycle treatment comprises: after the freezing treatment, the sample is thawed at room temperature, and the cycle treatment is carried out for more than 3 times; wherein the freezing temperature is below-20℃, and the single freezing time is 8-12h.

[0016] Further, the freezing temperature is-20℃ to-25℃.

[0017] Preferably, the freeze-thaw cycle treatment is carried out in a mold.

[0018] Preferably, after the preparation of the CNF-C / PVA composite hydrogel is completed, the CNF-C / PVA composite hydrogel is sterilely packaged and sterilized by ultraviolet rays.

[0019] The present application provides a cervical support, and the material components of the cervical support comprise any of the CNF-C / PVA composite hydrogels.

[0020] The cervical support comprises a main body part 1 made of any of the CNF-C / PVA composite hydrogels, wherein a cavity 2 is arranged in the main body part 1, and the cavity 2 is used for clamping the cervical position.

[0021] The cervical support is in a bowl-shaped structure.

[0022] The main body part 1 is configured to be fixed at the cervix, and the hollow cavity 2 is configured to accommodate the cervical tissue, so that the cervical support can be deformed and guided through the vagina to the cervical orifice position during the placement process.

[0023] The cervical support is customized according to the physiological structure of the patient to have a porous topological cervical support shape, which meets the treatment needs of most patients and can be stably placed at the cervix, thereby avoiding the displacement of the cervical support and the occurrence of slippage due to walking and other actions.

[0024] The hydrogel cervical support prepared by the prepared mold can meet the needs of most patients, and a few patients need to be customized according to specific needs.

[0025] The application provides application of the cervical support in preparation of a medical device for preventing premature birth or treating a pelvic floor dysfunction disease.

[0026] The application discloses a cervical support based on CNF-C / PVA composite hydrogel, which comprises a cervical support main body part and a cavity. The main body part is prepared from polyvinyl alcohol hydrogel with carboxylated nanocellulose fibers (CNF-C) as a reinforcing phase, and solves problems such as patient discomfort and multiple complications caused by high hardness and poor tissue adaptability of traditional silica gel materials. Through a carboxylated nanocellulose fiber (CNF-C) composite and dynamic crosslinking strategy, the mechanical properties of the application are regulated to dynamically match the cervical tissue of the human body, which can not only provide reliable support force, but also reduce mechanical damage to the mucosa. From the perspective of clinical application, the application can improve the treatment experience of patients with pelvic floor dysfunction diseases, reduce surgical dependence and relieve medical burden. The design idea of the application is to use polyvinyl alcohol with a specific alcoholysis degree and a polymerization degree as raw material, carboxylated nanocellulose fibers (CNF-C) as a reinforcing phase, and prepare polyvinyl alcohol composite hydrogel after multiple freeze-thaw cycles, so that the prepared composite hydrogel cervical support has balanced mechanical properties of high modulus, high strength and high toughness.

[0027] Advantages

[0028] (1) The application enhances polyvinyl alcohol (PVA) hydrogel by carboxylated nanocellulose fibers (CNF-C), combines a double crosslinking interpenetrating network structure (IPN) and a dynamic mechanical matching design, solves clinical pain points such as high hardness, low biocompatibility, high tissue irritation, poor individual adaptability and high risk of infection of traditional silica gel cervical supports, and ensures the biological safety of the application through in vitro stimulation experiments.

[0029] (2) Polyvinyl alcohol (PVA) and carboxylated nanocellulose fibers (CNF-C) are common and relatively reasonable raw materials on the market, and their large-scale procurement cost is low, which has obvious cost advantage for large-scale production, and is conducive to industrialized production and market promotion of subsequent products. At the same time, the preparation process used in the experiment, such as freeze-thaw cycle method and ultrasonic dispersion, has relatively simple equipment requirements and easy-to-control operation process, avoids complex and expensive production equipment investment, and further reduces the production cost.

[0030] (3) Carboxylated cellulose nanofibers (CNF-C) are dispersed and interwoven in the polyvinyl alcohol (PVA) network, avoiding local stress concentration through a stress dispersion mechanism. Electron microscopy results show that the carboxylated cellulose nanofibers (CNF-C) connect the upper and lower ends of the pores through physical entanglement, forming a continuous three-dimensional network structure. Due to the addition of carboxylated cellulose nanofibers (CNF-C), they play a reinforcing role in the polyvinyl alcohol (PVA) hydrogel network structure, avoiding structural damage caused by local stress concentration through a stress dispersion mechanism. Compared with pure polyvinyl alcohol (PVA) hydrogel, the mechanical strength of CNF-C / PVA composite hydrogel is significantly improved.

[0031] (4) CNF-C / PVA composite hydrogels are biodegradable, reducing the risk of environmental pollution from medical waste and aligning with the global trend of "green" medical devices. No toxic or harmful chemical cross-linking agents were used in the experiment, avoiding potential threats to the environment and human health from chemical residues. Furthermore, the solvents used in the experiment were primarily deionized water, which is widely available and pollution-free, consistent with green chemistry principles.

[0032] (5) The present invention can be given certain antibacterial properties by loading antibacterial agents. The hydrogel porous network can be loaded with slow-release antibacterial agents to achieve continuous antibacterial effect; and the fiber network of carboxylated nanocellulose fibers (CNF-C) can block bacterial colonization and achieve physical antibacterial effect.

[0033] (6) This invention provides a safer and more comfortable treatment option for patients with cervical insufficiency. Its universal design reduces individual dependence and can cover the needs of more than 90% of patients. Only a few patients need to customize according to their needs, which significantly reduces production costs and waiting period. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of the macroscopic structure of the present invention; wherein 1 is the main body; 2 is the cavity;

[0035] Figure 2 This is a schematic diagram of the cross-sectional structure of the present invention;

[0036] Figure 3 The Fourier transform infrared spectrum of Example 3 is shown below.

[0037] Figure 4 This is a SEM test image from Example 4;

[0038] Figure 5 This is the stress-strain curve diagram for Example 5;

[0039] Figure 6 This is the stress-strain curve diagram for Example 6. Detailed Implementation

[0040] The application will be further described in connection with the following detailed description. It should be understood that the following examples are intended to illustrate the application and are not intended to limit the scope of the application. Moreover, it should be understood that modifications can be made by those skilled in the art with the benefit of the teachings herein without departing from the scope of the application.

[0041] The test materials and reagents used in the following examples, unless otherwise specified, can be obtained commercially.

[0042] Unless otherwise specified, the specific techniques or conditions in the examples can be carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0043] The following polyvinyl alcohol (PVA) raw materials were provided by Anhui Wanwei Group Co., Ltd.:

[0044] PVA1788 refers to a degree of polymerization of 1700 and an alcoholysis degree of 88%; PVA22-99H refers to a degree of polymerization of 2200 and an alcoholysis degree of 99%; and PVA23-99H refers to a degree of polymerization of 2300 and an alcoholysis degree of 99%.

[0045] The carboxylated nanocellulose fiber (CNF-C) was obtained from:

[0046] The carboxylated nanocellulose fiber CNF-J6424CP was purchased from Shenzhen Sailuonano Technology Co., Ltd., with a fiber diameter of 4-10 nm, a length of 200 nm, and a carboxyl content of 1.2 m mol / g;

[0047] The carboxylated nanocellulose fiber CNF-C916412 was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd., with a fiber diameter of 4-10 nm, a length of 200 nm, and a carboxyl content of 2 m mol / g;

[0048] The carboxylated nanocellulose fiber CNF-TL-001 was purchased from Nanjing Tianlu Nanotechnology Co., Ltd., with a fiber diameter of 4-10 nm, a length of 200 nm, and a carboxyl content of 3 m mol / g.

[0049] The test standards and methods involved in the examples and comparative examples are as follows:

[0050] The mechanical property tests were all completed using a universal material testing machine, and the test standard was referred to YY / T1435-2016.

[0051] The tensile property test cuts the hydrogel sample into a long strip shape with a length of 3.5 cm and a cross-sectional area of 20 cm², the clamping distance is 2 cm, the tensile speed is 200 mm / min, the breaking stress and breaking elongation of the hydrogel sample are measured, the arithmetic mean value is taken, and the stress-strain curve is obtained; the compression property test places the hydrogel in the center position of the universal material testing machine round table, the size height is 15 mm, the diameter is 35 mm, the sample shape is regular, which is a cylindrical shape, the compression speed is 100 mm / min, the compression pressure is set to 120 N, the compression strain and compression stress of the hydrogel sample are measured, the arithmetic mean value is taken, and the stress-strain curve is obtained.

[0052] Test standard of mechanical properties of cervical support:

[0053] According to the stress-strain curve obtained by the tensile property test, the area of the stress-strain curve is calculated, that is, the toughness of the hydrogel, the better the toughness, the stronger the ability of the hydrogel to resist fracture; according to the stress-strain curve obtained by the compression property test, the stress / strain ratio in the elastic stage is calculated to obtain the compression modulus.

[0054] The clinical manifestations of different compression moduli are shown in Table 1:

[0055] Table 1

[0056] Example 1

[0057] The preparation method of the CNF-C / PVA composite hydrogel is as follows:

[0058] 20 g of PVA22-99H flocculation is accurately weighed and placed in a 150 mL beaker, 80 mL of deionized water is added, a PVA solution suspension with a mass fraction of 20% is prepared, then carboxylated nanocellulose fibers are introduced into the PVA suspension according to the mass ratio of PVA22-99H:CNF-C=1:0.15 to prepare a fiber-reinforced hydrogel composite solution, the solution is placed in a 99 ℃ constant temperature water bath for fully stirring for 30 min, so that the PVA / CNF-C is fully dissolved, and the solution is transparent and viscous. Then put it into a 60 ℃ ultrasonic machine for 20 min of ultrasonic defoaming. After the reaction time reaches, pour into the mold. Place the sample in a refrigerator with a freezing temperature of-23 ℃ for single freezing for 12 h, then take out and thaw at room temperature, repeat 4 times.

[0059] In this example, the carboxylated nanocellulose fiber has a carboxyl content of 2 m mol / g.

[0060] Example 2

[0061] The preparation method of the CNF-C / PVA composite hydrogel is as follows:

[0062] PVA 23-99H powder was accurately weighed at 20 g in a 150 mL beaker, 80 mL of deionized water was added to prepare a PVA solution suspension with a mass fraction of 20%, and then carboxylated nanocellulose fibers were introduced into the PVA suspension according to a mass ratio of PVA 23-99H: CNF-C = 1:0.15. The solution was placed in a constant temperature water bath at 99°C and stirred for 30 min to fully dissolve the PVA / CNF-C, and the solution was transparent and viscous. Then it was placed in an ultrasonic machine at 60°C for 20 min. After the reaction time reached, it was poured into a mold. The sample was placed in a refrigerator at a freezing temperature of -23°C for single freezing for 12 h, then taken out, thawed at room temperature, and repeated 4 times.

[0063] In this example, carboxylated nanocellulose fibers with a carboxyl content of 2 mmol / g were used.

[0064] Comparative Example 1

[0065] This example provides a preparation method for preparing a hydrogel using pure PVA as a raw material, which includes the following steps:

[0066] PVA 22-99H flocculation was accurately weighed at 20 g in a 150 mL beaker, 80 mL of deionized water was added to prepare a PVA solution suspension with a mass fraction of 20%, and then the solution was placed in a constant temperature water bath at 99°C and stirred for 30 min to fully dissolve the PVA / CNF-C, and the solution was transparent and viscous. Then it was placed in an ultrasonic machine at 60°C for 20 min. After the reaction time reached, it was poured into a mold. The sample was placed in a refrigerator at a freezing temperature of -23°C for single freezing for 12 h, then taken out, thawed at room temperature, and repeated 4 times.

[0067] Comparative Example 2

[0068] The preparation method of CNF-C / PVA composite hydrogel is as follows:

[0069] PVA 1788 powder was accurately weighed at 20 g in a 150 mL beaker, 80 mL of deionized water was added to prepare a PVA solution suspension with a mass fraction of 20%, and then carboxylated nanocellulose fibers were introduced into the PVA suspension according to a mass ratio of PVA 1788: CNF-C = 1:0.15 to prepare a fiber-reinforced hydrogel composite solution. The solution was stirred at room temperature for 15 min until the PVA / CNF-C was fully dissolved, and then poured into a mold. The sample was placed in a refrigerator at a freezing temperature of -23°C for single freezing for 12 h, then taken out, thawed at room temperature, and repeated 4 times.

[0070] In this example, carboxylated nanocellulose fibers with a carboxyl content of 2 mmol / g were used.

[0071] Comparative Example 3

[0072] The preparation method of the CNF-C / PVA composite hydrogel is as follows:

[0073] 20 g of PVA22-99H powder was accurately weighed into a 150 mL beaker, 80 mL of deionized water was added, and a PVA solution suspension with a mass fraction of 20% was prepared. Then, carboxylated nanocellulose fibers were introduced into the PVA suspension at a mass ratio of PVA22-99H:CNF-C=1:0.15. The solution was placed in a 99 ℃ constant temperature water bath for fully stirring for 30 min to make PVA / CNF-C fully dissolved, and the solution was transparent and viscous. Then, it was placed in a 60 ℃ ultrasonic machine for ultrasonic defoaming for 20 min. After the reaction time reached, it was poured into a mold. The sample was placed in a refrigerator with a freezing temperature of -23 ℃ for single freezing for 12 h, then taken out, and thawed at room temperature, and repeated 4 times. The swelling imbalance of the cervical support caused by the increased brittleness of the hydrogel cervical support caused the collapse of the cavity structure, and the shaped medical cervical support could not be prepared.

[0074] In this example, carboxylated nanocellulose fibers with a carboxyl content of 3 m mol / g were used.

[0075] Comparative Example 4

[0076] The preparation method of the CNF-C / PVA composite hydrogel is as follows:

[0077] 20 g of PVA22-99H powder was accurately weighed into a 150 mL beaker, 80 mL of deionized water was added, and a PVA solution suspension with a mass fraction of 20% was prepared. Then, carboxylated nanocellulose fibers were introduced into the PVA suspension at a mass ratio of PVA22-99H:CNF-C=1:0.15. The solution was placed in a 99 ℃ constant temperature water bath for fully stirring for 30 min to make PVA / CNF-C fully dissolved, and the solution was transparent and viscous. Then, it was placed in a 60 ℃ ultrasonic machine for ultrasonic defoaming for 20 min. After the reaction time reached, it was poured into a mold. The sample was placed in a refrigerator with a freezing temperature of -23 ℃ for single freezing for 12 h, then taken out, and thawed at room temperature, and repeated 4 times.

[0078] In this example, carboxylated nanocellulose fibers with a carboxyl content of 1.2 m mol / g were used.

[0079] Example 3

[0080] The hydrogel prepared in Example 1 was tested by Fourier infrared spectroscopy, and the results are shown in Figure 3 As can be seen from the figure, Figure 3The Fourier infrared spectrum of CNF-C / PVA composite hydrogel is shown, and it can be seen that the infrared absorption of -OH, -CH2-, C=O and -C-O- is observed at 3288 cm -1 , 2905 cm -1 , 1645 cm -1 and 1086 cm -1 , respectively, and compared with the Fourier infrared spectrum of pure PVA hydrogel, the peak value of C=O is observed more, which proves that CNF-C and PVA form a chemical crosslinking network through chemical reaction, thereby enhancing the mechanical strength of CNF-C / PVA composite hydrogel. That is, the abundant carboxylic acid groups (-COOH) on the surface of CNF-C form a physical crosslinking network with the hydroxyl groups (-OH) of PVA through hydrogen bonding, and at the same time, the carboxylic acid groups esterify with PVA under weak acidic conditions to generate dynamic covalent ester bonds (-COO-PVA), which makes CNF-C / PVA composite hydrogel construct a chemical crosslinking network on the basis of physical crosslinking, forming a "physical-chemical" double crosslinking IPN structure.

[0081] Example 4

[0082] The hydrogels prepared in Comparative Example 1 and Example 1 were subjected to SEM test, and the microstructures of the two were characterized. As shown in Figure 4 , the pore wall of pure PVA hydrogel is smooth and the surface is relatively flat. Through the SEM image of CNF-C / PVA composite hydrogel, it can be clearly seen that CNF-C is dispersed and interwoven in the gel network. These nanofibers connect the upper and lower ends of the pores through physical entanglement, playing a key supporting role. This structure makes the pore size distribution of the composite hydrogel significantly narrow, and the microstructure presents a continuous and irregular three-dimensional network porous structure with extremely rich pores. In the process of stress, since carboxylated nanocellulose fibers are added, they play a role in enhancing the skeleton in the PVA hydrogel network structure, and through stress dispersion mechanism, the structure damage caused by local stress concentration is avoided, so the CNF-C / PVA composite hydrogel can effectively resist deformation, thereby showing good mechanical stability.

[0083] Example 5

[0084] The CNF-C / PVA composite hydrogel medical cervical support prepared in Examples 1-2 and Comparative Example 2 was subjected to mechanical property test, and the stress-strain curve obtained is shown in Figure 5 . As shown in Figure 5As shown, comparing the stress-strain curves of the cervical pessaries obtained in Example 1 and Examples 2 and 2, it can be seen that the curve in Example 2 has the largest elongation at break, meaning its extension range on the strain axis is the longest. Compared with PVA22-99H and PVA23-99H, PVA1788 has a lower degree of alcoholysis (88%), can dissolve at room temperature, and has better ductility. However, in the application of cervical pessaries, they need to have a certain support capacity to support the cervix and maintain its normal physiological function. Although PVA1788 has good ductility, its fracture strength is relatively low, as can be seen from the curve. This means that it will reach its stress limit and fail earlier when subjected to external force, failing to provide sufficient support.

[0085] Mechanical properties of the CNF-C / PVA composite hydrogel medical cervical support prepared in Example 2 and Comparative Example 2 were tested, and the stress-strain curves obtained are shown below. Figure 5 As shown. Figure 5 As shown, compared to PVA23-99H, PVA22-99H exhibits the highest fracture strength, meaning that under the same strain conditions, PVA22-99H can withstand a higher external force. The curve trend of PVA23-99H is similar to that of PVA22-99H, but its fracture strength is slightly lower. This is because the degree of polymerization of PVA23-99H (2300) is higher than that of PVA22-99H (2200). A higher degree of polymerization (molecular weight) results in longer molecular chains, and a significant increase in the degree of entanglement of these long molecular chains in solution or gel networks. Figure 5 As shown, under the same degree of hydrolysis (99%) and preparation conditions, the compression / elastic modulus of the composite hydrogel decreases with increasing degree of polymerization, while the tensile properties at break are improved.

[0086] pass Figure 5 The stress-strain curves show that the compressive modulus of PVA1788 is less than 150 kPa, indicating that PVA1788 does not meet the mechanical performance requirements for medical cervical supports. The compressive modulus of PVA23-99H is in the 150-200 kPa range, while that of PVA22-99H is in the 200-250 kPa range, achieving a more ideal support effect.

[0087] Example 6

[0088] Mechanical properties of CNF-C / PVA composite hydrogel medical cervical supports prepared in Comparative Example 1, Example 1, Comparative Example 3, and Comparative Example 4 were tested, and the stress-strain curves obtained are shown below. Figure 6 As shown. Figure 6As shown, the compression modulus of the hydrogel without adding carboxylated nanocellulose fibers is less than 50 kPa, and the mechanical strength of the prepared cervical support is insufficient and the fatigue resistance is poor; after adding carboxylated nanocellulose fibers with a carboxyl content of 1.2 mmol / g, the compression strength of the medical cervical support is greatly improved, but the compression modulus is still less than 150 kPa, which cannot meet the support performance of the medical cervical support; after adding carboxylated nanocellulose fibers with a carboxyl content of 2 mmol / g, the compression modulus of the medical cervical support is in the range of 200-250 kPa, achieving a relatively ideal support effect; when the carboxyl content is 3 mmol / g, the compression strength of the medical cervical support is greatly reduced, and the medical cervical support cannot be prepared.

[0089] Example 7

[0090] The results of the vaginal irritation test of the present application are characterized as follows:

[0091] Healthy experimental animals (such as female rabbits) are selected, and the animals need to be adaptively fed for 7-10 days before the experiment to adapt to the laboratory environment and feeding conditions, and a comprehensive health check is carried out, including body temperature monitoring, routine detection of vaginal secretions and visual inspection of vaginal mucosa, to exclude potential infected or diseased individuals and ensure the accuracy and reliability of the experimental results.

[0092] A short hose (6 cm) or a blunt cannula is selected to connect a syringe with a capacity greater than 1 mL as a dosing tool, and each set of syringe and catheter is dedicated to a single animal, and strict aseptic operation specifications are followed to avoid interference of external microorganisms with the experimental results. A special fixator or restraint device is used to fix the experimental animal, the hind limbs of the animal are fixed on the experimental table in a supine position, the tail of the animal is lifted to expose the vaginal orifice, and then the catheter treated with moisture is gently inserted into the vagina to avoid damage to the vaginal wall caused by violent operation. After injecting 1 mL of test sample, the catheter is withdrawn and disposed of in an appropriate manner.

[0093] Due to the difference in vaginal volume of individual animals, the test sample may overflow during or after injection, and the overflowed liquid can be wiped off with a sterile soft paper towel. The dosing frequency is set to once every 24 ± 2 hours, and the above steps are repeated for at least 5 consecutive days.

[0094] It is observed on the fourth day of the vaginal irritation experiment that a small amount of secretion is produced in the vagina of the rabbit injected with the domestic silica gel sample extract, while no secretion is produced in the hydrogel sample (the sample uses the composite hydrogel of Example 1). This indicates that the irritation of the present application to the animal vaginal mucosa is smaller than that of the silica gel cervical support, so the biocompatibility of the hydrogel cervical support is significantly better than that of the silica gel cervical support.

Claims

1. A CNF-C / PVA composite hydrogel, characterized in that, The CNF-C / PVA composite hydrogel is obtained from raw materials containing carboxylated nanocellulose fibers CNF-C and polyvinyl alcohol PVA through freeze-thaw cycle treatment. The carboxyl group content in the carboxylated nanocellulose fiber CNF-C is 1.7~2.5 mmol / g; the degree of alcoholysis of the polyvinyl alcohol PVA is above 98 mol%, and the degree of polymerization is 2200~2500.

2. The CNF-C / PVA composite hydrogel according to claim 1, characterized in that, The raw materials also contain antibacterial agents.

3. A method for preparing the CNF-C / PVA composite hydrogel according to any one of claims 1-2, comprising: Carboxylated nanocellulose fibers (CNF-C), polyvinyl alcohol (PVA), and water were mixed, stirred, defoamed, and then subjected to freeze-thaw cycles to obtain a CNF-C / PVA composite hydrogel.

4. The preparation method according to claim 3, characterized in that, The mass ratio of polyvinyl alcohol (PVA) to carboxylated nanocellulose fiber (CNF-C) is 1:0.1 to 1:0.

25.

5. The preparation method according to claim 3, characterized in that, The stirring is carried out at 25~100℃ for 10~30 minutes; the degassing is carried out by ultrasonic degassing.

6. The preparation method according to claim 3, characterized in that, The freeze-thaw cycle treatment involves freezing followed by thawing at room temperature, and repeating the cycle at least three times. The freezing temperature is below -20°C, and the freezing time for each cycle is 8 to 12 hours.

7. A cervical pessary, characterized in that, The material composition of the cervical support includes the CNF-C / PVA composite hydrogel as described in any one of claims 1-2.

8. The cervical support according to claim 7, wherein the cervical support comprises a main body (1) made of CNF-C / PVA composite hydrogel according to any one of claims 1-2, wherein the main body (1) has a cavity (2) for holding the cervix in place.

9. The use of the cervical support as described in claim 7 in the preparation of a medical device for preventing premature birth or treating pelvic floor dysfunction.

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