Degradable shape memory isolating membrane in uterine cavity and preparation method thereof

Abstract

The invention relates to the technical field of biological materials, in particular to an intrauterine degradable shape memory isolating membrane and a preparation method thereof. The raw materials of the isolating membrane at least comprise a compound of an artificial high-molecular compound and a natural high-molecular compound. The mass ratio of the artificial high-molecular compound to the natural high-molecular compound is (5-95): (95-5); the isolating membrane is used for loading the medicine and continuously releasing the medicine into the uterine cavity. The isolating membrane is folded and conveyed to a womb wound part after an operation, the purpose of automatically unfolding the isolating membrane to reach the womb wound part is achieved, and intrauterine adhesion is physically blocked. In addition, the isolating membrane can load bioactive medicines according to requirements, so that the functions of relieving pain or stimulating and continuously activating an endometrial basal layer are realized, the occurrence of uterine scars is inhibited, and the normal uterine fertility function of a patient can be recovered more quickly.

Description

Technical Field

[0001] The present invention relates to the technical field of biomaterials (IPC: A61L), and in particular to an intrauterine degradable shape memory isolation membrane and a preparation method thereof. Background Art

[0002] IUA (Intrauterine Adhesions) is a common gynecological disease. It is usually caused by endometrial damage and abnormal repair process after uterine surgery (such as curettage, cesarean section, etc.), resulting in the formation of fibrous adhesions between endometrial tissues. The hazards of IUA mainly include the following: (1) Menstrual abnormalities: Intrauterine adhesions may cause reduced menstrual volume or even amenorrhea, affecting women's menstrual cycle; (2) Infertility: Intrauterine adhesions may affect embryo implantation, leading to infertility or difficulty in pregnancy; (3) Habitual miscarriage: Adhesions may affect the normal development of the embryo and increase the risk of miscarriage. Changes in uterine cavity morphology: Adhesions may cause changes in uterine cavity morphology and affect the normal function of the uterus; (4) Chronic pelvic pain: Some patients may experience chronic pelvic pain; (5) Psychological impact: IUA and the fertility problems it brings may cause psychological pressure and impact on patients.

[0003] At present, the main method for treating IUA is to perform hysteroscopic intrauterine adhesion separation surgery; when the basal layer of the uterus is damaged, a barrier membrane is often implanted clinically to prevent the occurrence of adhesions; in the treatment of IUA, the barrier membrane plays a key role. First, as a barrier, it covers and protects the damaged uterine area, preventing further tissue damage and potential infection. Secondly, the barrier membrane reduces the contact between endometrial tissues through physical isolation, thereby reducing the possibility of adhesion formation. In addition, the barrier membrane can also serve as a drug sustained-release system to continuously provide therapeutic drugs to the damaged area, which helps to promote the repair and regeneration of endometrial tissue. As the barrier membrane gradually degrades, its degradation products may play a positive role in improving the local environment and promoting the healing process. Finally, the presence of the barrier membrane helps to maintain the integrity and morphology of the uterine cavity, creating favorable conditions for the recovery of the endometrium.

[0004] Although the IUA barrier membrane shows potential advantages in the treatment of intrauterine adhesions, it also faces some problems. First, most barrier membranes are biologically inert or non-degradable, requiring a secondary operation to remove, which poses potential safety hazards and risks. Secondly, the degradation cycle of the membrane does not match the female menstrual cycle and cannot provide continuous protection for an appropriate period of time. In addition, fragments or degradation products of the material may cause an immune response or change the acidity and alkalinity of the birth canal, causing diseases such as vaginitis. Thirdly, due to the shape problem, the barrier membrane material cannot be folded and curled arbitrarily, resulting in great discomfort during the implantation process. In addition, most barrier membranes are artificial polymers and cannot carry drugs, resulting in the inability to relieve pain after IUA surgery or promote wound repair.

[0005] Chinese Patent 202311646340.7 discloses an antibacterial diaphragm for preventing intrauterine adhesions and a preparation method thereof. An amine-rich macromolecular antibacterial agent is obtained by quaternizing and silanizing amine-rich macromolecules, and then the antibacterial silicone rubber is treated with an amine-rich macromolecular antibacterial agent to achieve an antibacterial effect. However, the material does not have a shape recovery function, nor can it load and release drugs. Chinese Patent 202111146422.6 discloses a multi-morphological adaptive bio-based endometrial repair material and a preparation method. By activating and grafting the base material, the base material is loaded with activation factors for use in a variety of soft tissue repairs. However, the grafting operation of this method is complicated, the process requirements are extremely high, and the operability of the technology is not strong.

[0006] In this context, providing an isolation membrane material that is safe and degradable, shape-controllable and foldable, capable of loading drugs, with readily available raw materials and simple process has become a technical problem that needs to be urgently solved in this field. Summary of the invention

[0007] In order to solve the problem that the isolation membrane in the above-mentioned prior art cannot effectively prevent postoperative adhesion, the present invention aims to provide a degradable shape memory isolation membrane in the uterine cavity and a preparation method thereof, by folding the isolation membrane and delivering it to the wound surface of the uterus after surgery, so as to achieve the purpose of self-expansion to the wound surface, and physically block the occurrence of intrauterine adhesion. In addition, the isolation membrane can be loaded with bioactive drugs according to demand to achieve the function of relieving pain or stimulating the continuous activation of the basal layer of the endometrium, inhibiting the occurrence of uterine scars, and enabling patients to restore normal uterine reproductive function more quickly.

[0008] The first aspect of the present invention provides an intrauterine degradable shape memory isolation membrane, the raw materials of which include at least a combination of artificial polymer compounds and natural polymer compounds; preferably, the mass ratio of the artificial polymer compounds to the natural polymer compounds is (5-95): (95-5).

[0009] More preferably, the mass ratio of the artificial polymer compound to the natural polymer compound is (5-15):(20-60); and most preferably, it is 8:40.

[0010] Preferably, the isolation membrane is loaded with drugs and continuously released into the uterine cavity.

[0011] Preferably, the artificial polymer compound includes polylactic acid (PLA), polyglycolic acid / polylactic acid copolymer (PGLA or PLGA), polyacetylglutamic acid (PAGA), polyethylene oxide / polybutylene terephthalate (PEO / PBTP), poly-p-dioxanone (PPDO), polyglycolic acid (PGA), polysaccharides, polyamino acids, polyesters and copolymers or blends of the above compounds.

[0012] Examples of polyesters include polycaprolactone (PCL), polyhydroxylbutyrate valerate (PHBV), polybutylene succinate (PBS), polyglycerol sebacate (PGS), polyhydroxyalkanoates (PHA), polyorthoesters (POE), and polybutylene succinate (PBT).

[0013] Preferably, the artificial polymer compound includes PLA or PCL.

[0014] Preferably, the PLA may further be L-polylactic acid (poly (L-lactic acid, PLLA).

[0015] Preferably, the pH of the degradation product of the artificial macromolecular compound is 3-7, which is neutral or slightly acidic.

[0016] Preferably, the natural polymer compound includes acellular matrix and / or animal protein.

[0017] Further preferably, the animal protein includes at least one of gelatin, fish glue, bone glue, shellac and fibrin glue.

[0018] Still further preferably, the animal protein comprises gelatin.

[0019] Preferably, the drug includes at least one of estrogen drugs, drugs for increasing capillary blood supply, and immunomodulatory drugs.

[0020] Examples of estrogen drugs include, but are not limited to, 17β-estradiol, estrone, estriol, and 17β-estradiol derivatives (e.g., estradiol benzoate, estradiol valerate, ethinyl estradiol, ethinyl estradiol ether, and estrone). Compared with oral or other forms of estrogen administration, the estrogen of the present invention can be locally targeted and released under the load of the isolation membrane, stimulating endometrial hyperplasia, and will not cause side effects such as hormone disorders due to high-dose administration, and has strong safety.

[0021] Examples of drugs that increase capillary blood supply include, but are not limited to, aspirin, sildenafil citrate, pentoxifylline (PTX), vitamin E, L-arginine, low molecular weight heparin (such as heparin sodium), etc., which can increase capillary blood supply and improve endometrial blood flow.

[0022] As an example of immunomodulatory drugs, colony stimulating factors that can regulate local immunity in the uterine cavity can be selected, including but not limited to granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), etc.

[0023] The second aspect of the present invention provides a method for preparing a degradable shape memory isolation membrane in the uterine cavity, the preparation steps of the isolation membrane comprising:

[0024] S1. mixing and dissolving an artificial polymer compound and a natural polymer compound in a solvent, and electrospinning to obtain a fiber membrane;

[0025] S2. physically crushing the fiber membrane and then freeze-drying it to obtain fiber membrane fragments;

[0026] S3. The fiber membrane debris is subjected to thermal cross-linking treatment to obtain an isolation membrane substrate;

[0027] S4. Perform chemical cross-linking treatment on the isolation film substrate to obtain an isolation film finished product.

[0028] Preferably, in the step S1, before electrospinning, the artificial polymer compound and the natural polymer compound are mixed and added to a solvent, and stirred overnight at 200-1000 rpm until completely dissolved.

[0029] The solvent in step S1 is a commonly used solvent in the art, and is not particularly limited as long as it can achieve the purpose of dissolution; for example, hexafluoroisopropanol, trifluoroethanol, acetic acid, etc.

[0030] Preferably, the conditions for the electrospinning are: voltage 10-20 kV, propulsion rate 2-8 mL / h, and receiving distance 5-15 cm.

[0031] Further preferably, the conditions for the electrospinning are: voltage 15 kV, propulsion rate 5 mL / h, and receiving distance 10 cm.

[0032] The present invention does not specifically limit the method of physical crushing, and the crushing method commonly used in the art can be used.

[0033] Preferably, the temperature of the thermal cross-linking treatment in step S3 is higher than the melting point of the artificial polymer compound.

[0034] More preferably, the temperature of the thermal crosslinking treatment is 170-240° C., and the time of the thermal crosslinking treatment is 0.5-5 h.

[0035] Preferably, the chemical cross-linking treatment in step S4 is specifically: immersing the isolation membrane substrate in a cross-linking solution to perform a cross-linking reaction to obtain the isolation membrane.

[0036] Preferably, the cross-linking solution is an aqueous solution containing a cross-linking agent.

[0037] Further preferably, the cross-linking agent includes at least one of glutaraldehyde, ethanol, genipin, N-hydroxysuccinimide or 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and hyaluronic acid.

[0038] More preferably, the cross-linking agent includes N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and hyaluronic acid (HA).

[0039] Preferably, the mass ratio of EDC, NHS and HA is (1-5):(0.1-2):(2-10); more preferably 3:0.5:5.

[0040] Preferably, the mass ratio of the isolation membrane substrate to the drug is (10-90): (90-10).

[0041] Preferably, the mass ratio of the cross-linking agent to the drug is (0.8-3):1.

[0042] Preferably, the drug is added to the cross-linking solution, and the drug is evenly dispersed inside the isolation membrane obtained after the chemical cross-linking reaction of the isolation membrane substrate.

[0043] Preferably, the degradation period of the isolation membrane prepared by the present invention is 7-30 days; further preferably, the degradation period of the isolation membrane is 3-21 days.

[0044] Preferably, the isolation film prepared by the present invention can recover its shape within 1 hour after being folded or curled by 180 degrees and contacting with water; more preferably, it can recover its shape within 1 minute.

[0045] More preferably, the isolation membrane prepared in the present invention can recover its shape within 1 second after being folded or curled by 180° and then immersed in an aqueous solution.

[0046] More preferably, the isolation film prepared by the present invention can recover its shape within 5 seconds after being folded or curled by 180° and then wetted by water drops.

[0047] The shape of the isolation membrane can be flexibly designed based on the IUA treatment situation. In actual use, the isolation membrane is placed in a delivery device, and the delivery device is provided with a push rod, which pushes the isolation membrane to the target position for implantation in the uterine cavity. Preferably, the isolation membrane is designed to be large at the upper end and small at the lower end, such as an inverted trapezoid, an inverted triangle, an inverted pear or a heart shape. After implantation, the upper end of the isolation membrane corresponds to the fundus of the uterus, and the lower end corresponds to the intrauterine opening of the cervix.

[0048] Preferably, the isolation membrane is in the shape of an inverted trapezoid, the length of the lower base of the trapezoid (the upper end of the isolation membrane, located at the fundus of the uterus) is 20-40mm, the length of the upper base of the trapezoid (the lower end of the isolation membrane, located at the internal os of the cervix) is 3mm-20mm, and the height of the trapezoid is 20mm-40mm.

[0049] Preferably, the thickness of the isolation film is 0.1 mm-10 mm, more preferably 0.2 mm-2 mm.

[0050] During processing, the required thickness is first pressed out when forming the film as needed, and then it is cut as needed to obtain a separator of the target shape and size.

[0051] When the basal layer of the uterus is damaged, clinically, an isolation membrane is mainly implanted to prevent adhesion. However, on the one hand, the traditional isolation membrane has poor degradability and needs to be removed twice; on the other hand, it is difficult to restore the shape after folding, and the implantation process is accompanied by great discomfort; these problems limit the use of isolation membranes. Compared with traditional prefabricated shape isolation membranes, the present invention provides an IUA isolation membrane with shape memory function, which shows unique advantages in the treatment of intrauterine adhesions. First, the shape of this material is flexible and controllable, and it can be adaptively adjusted according to the specific shape of the uterine cavity to ensure better fit with the uterine cavity. Secondly, this material has shape memory and can quickly return to its original shape after absorbing water. This feature helps to maintain the proper position of the isolation membrane in the uterine cavity. In addition, the isolation membrane of the present invention has suitable softness and foldability, which can reduce potential damage to the uterine cavity during surgery.

[0052] On the other hand, the isolation membrane of the present invention can load drugs, and the isolation membrane material with shape memory properties has controllable drug release capacity, allowing more precise management of therapeutic doses. At the same time, the isolation membrane material has good biocompatibility, reducing possible adverse reactions to patients. After completing the therapeutic function, the biodegradability of the material ensures that it is safely eliminated from the body, avoiding the risk of long-term retention in the patient's body. In addition, the degradation products of the material are neutral or weakly acidic, which has little effect on the weakly acidic environment of the vagina, avoiding the occurrence of inflammation. At the same time, thanks to the adaptability and recovery ability of the isolation membrane, it can bring a more comfortable and satisfactory experience to patients, greatly reducing the discomfort and pain of the treatment process.

[0053] Beneficial effects:

[0054] The present invention provides a degradable shape memory isolation membrane in the uterine cavity and a preparation method thereof, which has the following advantages:

[0055] (1) The isolation membrane is prepared by compounding a specific artificial polymer compound with a natural polymer compound, and PCL and gelatin are particularly preferred. On the one hand, the obtained isolation membrane can effectively physically isolate intrauterine adhesions, and on the other hand, the material has good biodegradability and can be degraded and discharged in the human body, reducing the risk of retention and secondary operation;

[0056] (2) The obtained isolation membrane can effectively load drugs into the uterine cavity and continuously release the drugs into the uterine cavity, exerting a therapeutic effect while physically isolating the drug; and by adding drugs during the chemical cross-linking reaction, the drugs can be evenly dispersed in the three-dimensional network of the isolation membrane, and the drug release process is stable and controllable, ensuring accurate control of the drug dosage;

[0057] (3) Under the selection of specific polymer compounds, the isolation membrane can be given excellent shape memory function through a specific preparation process of electrospinning-crushing and drying-thermal crosslinking-chemical crosslinking. The obtained isolation membrane has foldability and can unfold itself after contacting water. It can be adaptively adjusted according to the specific shape of the uterine cavity to ensure better fit;

[0058] (4) The present invention further improves the shape memory ability of the isolation membrane through the two-step action of thermal crosslinking and chemical crosslinking. The obtained isolation membrane can quickly return to its original shape after being soaked in water; it can weaken the potential damage of the material to the uterine cavity during IUA treatment and improve the patient's experience during the treatment process;

[0059] (5) The raw materials of the present invention are easily available, the process operation is simple, and the obtained isolation membrane has excellent comprehensive performance, which provides an effective solution for IUA treatment and is suitable for wide promotion in the field of gynecological disease treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] Figure 1 . Fourier infrared images of the isolation membrane and gelatin and pure PLLA of Example 1; (blue line: Example 1, red line: gelatin, black line: PLLA)

[0061] Figure 2 . Scanning electron microscope image of the material during the preparation of the isolation membrane in Example 1; (a in the figure is the fiber membrane debris before cross-linking, b is the isolation membrane substrate after thermal cross-linking, and c is the isolation membrane after chemical cross-linking)

[0062] Figure 3 .Example 1 Compression folding diagram of the isolation film immersed in water; (a is the initial isolation film, b is the isolation film folded 180°, c is the isolation film after folding immersed in water, d is the case of immersion in water for 0s, e is the case of immersion in water for 0.5s, and f is the case of immersion in water for 1s)

[0063] Figure 4 .Example 1 Compression folding diagram of the isolation film wetted by water droplets; (a is the initial isolation film, b is the isolation film folded 180°, c is the isolation film wetted by water droplets after folding, d is the situation 0s after water droplets are wetted, e is the situation 1s after water droplets are wetted, f is the situation 2s after water droplets are wetted, and g is the situation 5s after water droplets are wetted)

[0064] Figure 5 . Comparison of degradation time of the isolation film and pure PLLA in Example 1; (red line: Example 1, black line: PLLA)

[0065] Figure 6 . Cumulative release curve of heparin from the isolation membrane of Example 1; (red line: pH is 7.4, black line: pH is 4).

[0066] Figure 7 . Actual pictures of the isolation film of Example 3 before and after thermal crosslinking (left picture: before thermal crosslinking, right picture: after thermal crosslinking). DETAILED DESCRIPTION

[0067] Note: The specifications and sources of the raw materials involved in the specific implementation of the present invention are as follows.

[0068] Gelatin: Porcine gelatin, gel strength ~100g Bloom, supplier: Shanghai Aladdin Biochemical Technology Co., Ltd.

[0069] PLLA: L-polylactic acid, intrinsic viscosity 0.8-1.5dl / g, supplier Suzhou Qihang Biotechnology Co., Ltd.

[0070] PCL: Polycaprolactone, molecular weight 8w, sourced from Suzhou Qihang Biotechnology Co., Ltd.

[0071] HA: relative molecular weight 20w, supplier: Liyang Biotechnology.

[0072] Example 1

[0073] In a first aspect, the present embodiment provides a degradable shape memory isolation membrane in the uterine cavity, wherein the raw materials of the isolation membrane include a compound of an artificial polymer compound and a natural polymer compound; specifically, 0.4 g of the artificial polymer compound (PLLA) and 2 g of the natural polymer compound (gelatin). The isolation membrane is loaded with a drug (heparin sodium) and continuously released into the uterine cavity.

[0074] The second aspect of this embodiment provides a method for preparing a degradable shape memory isolation membrane in the uterine cavity, and the steps of preparing the isolation membrane include:

[0075] S1. 2 g of gelatin and 0.4 g of PLLA were mixed in 20 mL of solvent (hexafluoroisopropanol), stirred at 600 rpm overnight until completely dissolved, and then electrospun to obtain a fiber membrane; the electrospinning conditions were: voltage 15 kV, propulsion rate 5 mL / h, and receiving distance 10 cm.

[0076] S2. Physically break the fiber membrane, specifically cut the fiber membrane into pieces of 1*1cm 2 size, then the shredded fiber membrane and tert-butyl alcohol were mixed at a solid-liquid ratio of 5 g / 150 mL, and the mixture was broken by high-speed stirring (10000 rpm for 30 min) to obtain an isolation membrane substrate dispersion; the isolation membrane substrate dispersion was transferred to a mold, frozen at -80°C overnight, and then freeze-dried for 3 days to obtain fiber membrane scraps;

[0077] S3. The fiber membrane debris is subjected to thermal cross-linking treatment, specifically at 190° C. for 2 h to obtain a separator substrate;

[0078] S4. Perform chemical cross-linking treatment on the isolation film substrate to obtain an isolation film finished product.

[0079] The chemical cross-linking treatment in step S4 is specifically as follows: preparing a cross-linking solution with added drugs, immersing the isolation membrane substrate in the cross-linking solution, slowly stirring, and cross-linking for 2 hours; then freezing the product in liquid nitrogen for 1 hour, and drying it in a freeze dryer for 3 days to obtain a finished isolation membrane.

[0080] The cross-linking solution with added drugs was prepared by adding a cross-linking agent (EDC 0.3 g, NHS 0.05 g, HA 0.5 g) and 0.5 g of sodium heparin to 50 mL of water and stirring for 30 min.

[0081] Example 2

[0082] The first aspect of this embodiment provides a degradable shape memory isolation membrane in the uterine cavity, the raw materials of the isolation membrane include a compound of an artificial polymer compound and a natural polymer compound; specifically, an artificial polymer compound (PCL) and a natural polymer compound (gelatin); the mass ratio of PCL to gelatin is 1:2.

[0083] The second aspect of this embodiment provides a method for preparing a degradable shape memory isolation membrane in the uterine cavity, and the steps of preparing the isolation membrane include:

[0084] S1. Add gelatin and PCL to a solvent (trifluoroethanol and acetic acid in a volume ratio of 500:1) and mix to obtain a polymer solution with a concentration of 10wt%; stir at 600rpm overnight until completely dissolved, and then electrospin to obtain a fiber membrane; the conditions for electrospinning are: voltage 20kv, propulsion rate 3mL / h, receiving distance 15cm.

[0085] S2. Physically break the fiber membrane, specifically cut the fiber membrane into pieces of 1*1cm 2 size, then the shredded fiber membrane and tert-butyl alcohol were mixed at a solid-liquid ratio of 5 g / 150 mL, and the mixture was broken by high-speed stirring (10000 rpm for 30 min) to obtain an isolation membrane substrate dispersion; the isolation membrane substrate dispersion was transferred to a mold, frozen at -80°C overnight, and then freeze-dried for 3 days to obtain fiber membrane scraps;

[0086] S3. The fiber membrane scraps are subjected to thermal cross-linking treatment, specifically, treatment at 70° C. for 2 hours, followed by natural cooling to obtain a finished isolation membrane.

[0087] Embodiment 3:

[0088] In a first aspect, the present embodiment provides a degradable shape memory isolation membrane in the uterine cavity, wherein the raw material of the isolation membrane is an artificial polymer compound, specifically an artificial polymer compound (PCL).

[0089] The second aspect of this embodiment provides a method for preparing a degradable shape memory isolation membrane in the uterine cavity, and the steps of preparing the isolation membrane include:

[0090] S1. PCL was added to a solvent (trifluoroethanol and acetic acid in a volume ratio of 500:1) and mixed to obtain a polymer solution with a concentration of 10 wt%; stirred at 600 rpm overnight until completely dissolved, and then electrospun to obtain a fiber membrane ( Figure 7 Left); the electrospinning conditions are: voltage 20 kV, propulsion rate 3 mL / h, and receiving distance 15 cm.

[0091] S2. The fiber film scraps are subjected to heat cross-linking treatment, specifically, at 70°C for 2 hours, followed by natural cooling to obtain a finished isolation film ( Figure 7 right).

[0092] Depend on Figure 7 As shown, the nanofiber membrane of Example 3 turns yellow after thermal crosslinking, and the nanofiber membrane is partially broken after thermal crosslinking, which shows that the fiber membrane material without adding natural polymer compounds and homogenization has poor mechanical properties and cannot meet the performance requirements of folding recovery.

[0093] Performance Testing

[0094] 1. Microscopic characterization of the isolation membrane

[0095] 1) Fourier infrared image

[0096] The Fourier infrared images of the shape memory isolation film prepared in Example 1 and the pure gelatin and PLLA are shown in Figure 1 .from Figure 1 It can be seen from the characteristic peaks in that the shape memory isolation membrane finally prepared in Example 3 already contains the characteristic peaks of gelatin and PCL (located at 3100-3400 and 1000-1800, respectively), which shows that gelatin and PLLA have been effectively combined in the shape memory isolation membrane material.

[0097] 2) SEM images

[0098] Example 1 Preparation of isolation membrane process material microscopic SEM image see Figure 2 .from Figure 2 It can be seen that after thermal cross-linking and chemical cross-linking, gelatin and PLLA have been effectively combined to form a whole.

[0099] 2. Memory folding of the isolation film

[0100] In order to simulate the uterine environment, the isolation membrane prepared in Example 1 was folded and exposed to water to observe its shape recovery; specifically, it was tested in two conditions: immersed in water and wetted with water drops. The test results are shown in Table 1. Figure 3 , Figure 4 .from Figure 3 , Figure 4 It can be seen that the obtained isolation membrane material can quickly return to its original state regardless of being immersed in water or wetted by water droplets; it is suitable for scenes containing small or large amounts of tissue fluid.

[0101] And, the memory folding performance results of Example 2 are Figure 3 , Figure 4 Similarly, it also has excellent memory folding properties.

[0102] 3. Degradability of the isolation membrane

[0103] The isolation membrane of Example 1 and pure PLLA were immersed in phosphate buffered saline (PBS) to observe the mass loss change of the materials (treatment temperature 37°C) and measure the degradation time. Figure 5 It can be seen that the isolation film of Example 1 has excellent degradability and can be completely degraded in 2-3 weeks.

[0104] 4. Drug release

[0105] like Figure 6 The cumulative release curve of heparin from the isolation membrane of Example 1 is shown; Figure 6 It can be seen that the heparin loaded on the isolation membrane of Example 1 can be released smoothly under both neutral and acidic conditions, and precise dosage control can be achieved.

Claims

1. A degradable shape memory isolation membrane in the uterine cavity, characterized in that: The raw materials of the isolation membrane at least include a compound of an artificial polymer compound and a natural polymer compound; the mass ratio of the artificial polymer compound to the natural polymer compound is (5-95): (95-5); The barrier membrane is loaded with drugs and continuously released into the uterine cavity.

2. The intrauterine degradable shape memory isolation membrane according to claim 1, characterized in that: The artificial polymer compound includes PLA, PAGA, POE, PEO / PBTP, PPDO, PHA, PGA, PGLA, polysaccharide, polyamino acid or polyester and copolymers or blends of the above compounds.

3. The intrauterine degradable shape memory isolation membrane according to claim 1, characterized in that: The natural high molecular compound includes acellular matrix and / or animal protein.

4. The intrauterine degradable shape memory isolation membrane according to claim 3, characterized in that: The animal protein includes at least one of gelatin, fish glue, bone glue, shellac and fibrin glue.

5. The intrauterine degradable shape memory isolation membrane according to claim 1, characterized in that: The drug includes at least one of estrogen drugs, drugs for increasing capillary blood supply, and immunomodulatory drugs.

6. A method for preparing a degradable shape memory isolation membrane in the uterine cavity according to any one of claims 1 to 5, characterized in that: The steps of preparing the isolation film include: S1. mixing and dissolving an artificial polymer compound and a natural polymer compound in a solvent, and electrospinning to obtain a fiber membrane; S2. physically crushing the fiber membrane and then freeze-drying it to obtain fiber membrane fragments; S3. The fiber membrane debris is subjected to thermal cross-linking treatment to obtain an isolation membrane substrate; S4. Perform chemical cross-linking treatment on the isolation film substrate to obtain an isolation film finished product.

7. The method for preparing the intrauterine degradable shape memory isolation membrane according to claim 6, characterized in that: The chemical cross-linking treatment in step S4 is specifically as follows: immersing the isolation film substrate in a cross-linking solution to perform a chemical cross-linking reaction to obtain an isolation film product; The cross-linking solution is an aqueous solution containing a cross-linking agent, and the cross-linking agent includes at least one of glutaraldehyde, ethanol, genipin, N-hydroxysuccinimide or 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and hyaluronic acid.

8. The method for preparing a degradable shape memory isolation membrane in the uterine cavity according to claim 7, characterized in that: The drug is added to the cross-linking solution; After step S4 is completed, the drug is dispersed inside the isolation membrane obtained by chemical cross-linking reaction of the isolation membrane substrate to achieve the loading purpose.

9. The method for preparing a degradable shape memory isolation membrane in the uterine cavity according to claim 6, characterized in that: The prepared isolation film product can be folded 180 degrees or curled and folded, and can recover its shape within 1 hour after contacting water.

10. The method for preparing a degradable shape memory isolation membrane in the uterine cavity according to claim 6, characterized in that: The degradation period of the prepared isolation film finished product at 37° C. is 7-30 days.

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