CN115969772A

CN115969772A - Preparation method and application of temperature-sensitive hydrogel

Info

Publication number: CN115969772A
Application number: CN202211621557.8A
Authority: CN
Inventors: 储筠; 凡孝菊; 钱松
Original assignee: Hunan Chuangjian Medical Instrument Co ltd
Current assignee: Hunan Chuangjian Medical Instrument Co ltd
Priority date: 2022-12-16
Filing date: 2022-12-16
Publication date: 2023-04-18
Also published as: WO2024125344A1

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method and application of a temperature-sensitive hydrogel. The temperature-sensitive hydrogel comprises poloxamer 407, poloxamer 188 and a solvent: the prepared temperature-sensitive hydrogel has good biocompatibility, does not pollute the affected part of a patient and clothes, and has high comfort level; the gel temperature is 32-36 ℃, the gel is a sol with good fluidity at room temperature, so that the administration of the medicine to the uterine cavity is convenient, the gel is rapidly solidified at the physiological temperature of the uterus, the physical isolation and the adhesion prevention of the wound surface after the uterine operation are completed, the rapid recovery of endometrium can be promoted, and the technical problems that the current endometrium repair preparation cannot ensure that the treatment medicine is closely contacted with the damaged part of the endometrium and can maintain the effective concentration for a long time and the treatment effect is poor are effectively solved.

Description

Preparation method and application of temperature-sensitive hydrogel

Technical Field

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method and application of a temperature-sensitive hydrogel.

Background

The uterus is the place for generating menstruation and gestating fetuses, and the normal endometrium can carry out self-repair and regeneration and plays a very important role in the physiological and reproductive functions of women. However, induced abortion, labor induction, uterine curettage, serious endocrine disorders, intrauterine infection, etc. can cause damage to the endometrium, thereby destroying the normal structure of the endometrium, causing increased tissue fibrosis, decreased glands, partial or total occlusion of the uterine cavity or/and the uterine cervix, and causing adhesion of the uterine cavity (IUA). The adhesion in the uterine cavity refers to the formation of adhesion or fibrous scar in the uterine cavity caused by the destruction of the basal layer of the endometrium due to infection or injury and other factors.

Currently, uterine cavity adhesion has become the second leading cause of secondary infertility in women. Moreover, the treatment of uterine cavity adhesion is a difficult problem in clinical practice at present, and particularly, the effect of the existing treatment means is poor in moderate and severe uterine cavity adhesion. For example, hysteroscopic adhesion separation and postoperative adhesion prevention include physical barriers such as intrauterine devices, hook balloons, regenerated cellulose anti-adhesion membranes and the like placed in the uterine cavity during operation, and are combined with postoperative use of large doses of estrogen to promote endometrial growth, so that the method is the main treatment method of the current IUA. But has poor treatment effect on moderate and severe uterine cavity adhesion patients. At present, pessaries, douches and oral tablets have been reported as endometrium repair preparations, but the curative effect is poor, mainly because the existing preparations cannot ensure that the therapeutic medicine is closely contacted with the damaged part of the endometrium and can maintain effective concentration for a long time.

In addition, the rapid secretion and renewal of endometrial mucus causes the rapid loss of therapeutic drugs in the cavity of the damaged uterus, so that the effective drug therapeutic concentration cannot be reached. Therefore, the medicine is loaded into the gel to act on the focus part for a long time, so that the loss of the medicine in delivery is reduced, and the curative effect of the medicine is improved.

At present, poloxamer is widely used as a temperature-sensitive material, but the current research mainly uses poloxamer as an auxiliary material, needs to combine other substances to realize the temperature-sensitive property and the treatment effect, has poor treatment effect and cannot stably exert the medicinal effect.

Disclosure of Invention

Aiming at the defects of the prior art and solving the problems, the invention provides a preparation method and application of a temperature-sensitive hydrogel; the prepared temperature-sensitive hydrogel can be injected to form gel in situ at a focus part, has long detention time at an administration part, can store a medicament, and can effectively solve the problem of short detention time of the medicament in a uterine cavity. Has the advantages of injectability, small wound, convenient administration, drug release delay, close contact with tissues and the like, and is suitable for in vivo local or implantation administration. The injection site has no obvious foreign body sensation, no toxicity or stimulation, good biocompatibility, no pollution to the affected part of the patient and clothes, and high comfort level. Meanwhile, the medicine has the function of anti-adhesion, and has good application prospect and important scientific significance for treating uterine cavity adhesion.

In order to achieve the technical purpose, the technical scheme provided by the invention is as follows:

the invention firstly provides a temperature-sensitive hydrogel which comprises the following components in percentage by mass:

poloxamer 407:20 to 25 percent;

poloxamer 188:2.5 to 7.5 percent.

Further, the solvent of the temperature-sensitive hydrogel is water.

Further, the water comprises deionized water, water for injection and normal saline.

Further, the solvent may be replaced with a phosphate buffer.

Further, the mass fraction of the poloxamer 407 is 20%, and the mass fraction of the poloxamer 188 is 2.5%.

The invention also provides a preparation method of the temperature-sensitive hydrogel, which comprises the following steps:

firstly, dissolving poloxamer 407 in a solvent, then adding poloxamer 188, stirring uniformly, and standing at a certain temperature to obtain a clear solution, namely the temperature-sensitive hydrogel.

Further, the certain temperature condition is 0-4 ℃.

Further, the standing time is 20-24h.

The temperature-sensitive hydrogel is applied to preparing products for preventing and treating uterine cavity adhesion and uterine fibrosis and promoting endometrial recovery.

Finally, the invention provides a composite preparation, which comprises the temperature-sensitive hydrogel.

Further, the composite preparation is used for preparing repair products of various damages of endometrium.

Further, the repair of various lesions of the endometrium includes the treatment of uterine cavity adhesion, uterine fibrosis resistance and the promotion of endometrial recovery.

Further, the application mode is specifically an in-situ injection mode in the uterine cavity.

The beneficial effect of this patent technique lies in:

(1) The temperature-sensitive hydrogel is prepared by controlling the dosage of poloxamer 407 and poloxamer 188, is a free-flowing liquid under the storage condition, can be transformed into a transparent solid or semisolid gel through phase transformation under the application condition, can be injected to form gel in situ at a focus part, has long retention time at an administration part, can store medicines, and can effectively solve the technical problem that the pure poloxamer cannot effectively treat uterine cavity adhesion.

(2) The temperature-sensitive hydrogel prepared by the invention has the advantages of injectability, small wound, convenient administration, drug release delay, close contact with tissues and the like, and is suitable for in-vivo local or implanted administration. The injection site has no obvious foreign body sensation, no toxicity or stimulation, good biocompatibility, no pollution to the affected part of the patient and clothes, and high comfort level. The poloxamer used has the function of anti-adhesion, and has good application prospect and important scientific significance for treating uterine cavity adhesion.

(3) The invention further sets the mass fraction of poloxamer 407 in the temperature-sensitive hydrogel to be 20-25%, and the mass fraction of poloxamer 188 to be 2.5-7.5%; the dosage is very important, the invention can realize the treatment of the uterine cavity adhesion only by using poloxamer through dosage control, and unexpected technical effects are obtained.

If the amount of poloxamer is not within the defined range of the present invention, the purpose of the present invention can not be achieved at all; if the dosage of poloxamer 407 is too low and the dosage of poloxamer 188 is too high, the final hydrogel product is not easy to gel when exceeding the normal body temperature of a human body, and the final hydrogel product directly flows out of the human body after being injected into the human body, so that the effect is not achieved completely; if poloxamer 407 is used in too high an amount and poloxamer 188 is used in too low an amount, the hydrogel product will gel at a lower temperature, which is not suitable for injection.

Drawings

FIG. 1 is a kinetic viscosity chart of the temperature-sensitive hydrogel of example 1 under different temperature conditions.

FIG. 2 is a morphogram of rat uterine tissue in the model group.

Fig. 3 is a morphology of rat uterine tissue in the treatment group.

FIG. 4 is a white light scan of the left uterine scar (MASSON) of rats in the model group.

FIG. 5 is a white light scan of the right uterine scar (MASSON) of rats in the model group.

Fig. 6 is a white light scan of the left uterine scar (MASSON) of rats in the treatment group.

Fig. 7 is a white light scan of the right uterine scar (MASSON) of rats in the treatment group.

FIG. 8 is a white light scan of the left endometrial cells (HE) of rats in the model group.

FIG. 9 is a white light scan of right endometrial cells (HE) from rats in the model group.

Fig. 10 is a white light scan of left endometrial cells (HE) from rats in the treatment group.

Fig. 11 is a white light scan of right endometrial cells (HE) from rats in the treatment group.

Figure 12 is the endometrial thickness of rats in the model and treatment groups.

Detailed Description

Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.

It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In addition, for numerical ranges in the present disclosure, it is understood that each intervening value, to the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.

It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification; the description and examples are intended to be illustrative only.

The invention provides a temperature-sensitive hydrogel, which comprises:

a. poloxamer: poloxamer 407 (HP 407), poloxamer 188 (HP 188)

b, solvent: water;

the mass fraction of poloxamer 407 in the temperature-sensitive hydrogel is 20-25%, and the mass fraction of poloxamer 188 is 2.5-7.5%.

The preparation method of the temperature-sensitive hydrogel comprises the following steps: firstly, dissolving poloxamer 407 in a solvent to enable the mass fraction of the poloxamer to be 20-25%; adding poloxamer 188 to make the mass fraction of poloxamer 2.5-7.5%, stirring uniformly, standing at a certain temperature to obtain a clear solution, i.e. the temperature-sensitive hydrogel.

Preliminary experiment 1:

the preparation method of the temperature-sensitive hydrogel comprises the following steps of firstly dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 20%; then adding poloxamer 188 to make the mass fraction of the gel be 2.5%, uniformly stirring, standing for 24h at the temperature of 4 ℃ to obtain a clear solution, namely the temperature-sensitive hydrogel (the total amount is 25 g); the gel temperature was measured and the results are shown in Table 1.

Preliminary experiment 2:

the preparation method of the temperature-sensitive hydrogel comprises the steps of firstly dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 22.5%; then adding poloxamer 188 to make the mass fraction of the gel be 5%, uniformly stirring, standing for 24h at the temperature of 4 ℃ to obtain a clear solution, namely the temperature-sensitive hydrogel (the total amount is 25 g); the gel temperature was measured and the results are shown in Table 1.

Preliminary experiment 3:

the preparation method of the temperature-sensitive hydrogel comprises the following steps of firstly dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 25%; then adding poloxamer 188 to make the mass fraction of the gel be 7.5%, uniformly stirring, standing for 24h at the temperature of 4 ℃ to obtain a clear solution, namely the temperature-sensitive hydrogel (the total amount is 25 g); the gel temperature was measured and the results are shown in Table 1.

TABLE 1 Pre-experiment of the mass fractions of the components and the corresponding gelling temperatures

According to the preliminary experiments 1-3, the gel temperature of the prepared temperature-sensitive hydrogel is 32-36 ℃ within the dosage range limited by the invention; the temperature-sensitive hydrogel prepared in the range can be used for the anti-adhesion treatment of the uterus; the gel is a sol body with good fluidity at room temperature, is convenient for administration in uterine cavity, is rapidly gelled and solidified at physiological temperature of uterus, completes physical isolation on wound surface after uterine operation, prevents adhesion, and can promote rapid recovery of endometrium.

Comparative example 1:

the preparation method of the temperature-sensitive hydrogel comprises the steps of firstly dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 27.5%; then adding poloxamer 188 to make the mass fraction of the gel be 1.5%, stirring uniformly, standing at 4 deg.C for 24h to obtain clear solution, and obtaining temperature sensitive hydrogel (total amount is 25 g); the gel temperature was measured and the results are shown in Table 2.

Comparative example 2:

the preparation method of the temperature-sensitive hydrogel comprises the steps of firstly dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 17.5%; then adding poloxamer 188 to make the mass fraction of the gel be 10%, uniformly stirring, standing for 24h at the temperature of 4 ℃ to obtain a clear solution, namely the temperature-sensitive hydrogel (the total amount is 25 g); the gel temperature was measured and the results are shown in Table 2.

TABLE 2 comparative examples the mass fractions of the components and the corresponding gelling temperatures

As can be seen from comparative examples 1-2, changing the respective components directly affects the gelation temperature; as in comparative example 1, the gelling temperature was 18 ℃, which gelled at room temperature, which was not conducive to transportation, storage and injection; comparative example 2, the gelling temperature reached 40 ℃, which was much higher than the human body temperature, was not easy to gel in human body, and was easy to flow out of body after injection, still not beneficial to application.

Example 1:

1. selecting raw materials:

a. poloxamer: poloxamer 407, poloxamer 188;

b, solvent: deionized water;

the components of the temperature-sensitive hydrogel of the present invention are shown in Table 3.

TABLE 3 proportion of the components (mass fraction)

2. The preparation method of the temperature-sensitive hydrogel comprises the following steps:

firstly, dissolving poloxamer 407 in deionized water to enable the mass fraction of the poloxamer to be 20%; and then adding poloxamer 188 to ensure that the mass fraction of the poloxamer 188 is 2.5%, uniformly stirring, and standing for 24 hours at the temperature of 4 ℃ to obtain a clear solution, namely the temperature-sensitive hydrogel.

The gelation temperature of the temperature-sensitive hydrogel prepared in this example is shown in table 1, and the gelation temperature of the temperature-sensitive hydrogel is 36 ± 0.2 ℃, and the temperature-sensitive hydrogel is subjected to rheological detection, as shown in fig. 1, which is a dynamic viscosity graph based on rheology, and the viscosity of the temperature-sensitive hydrogel decreases with the increase of the shear rate at a fixed temperature of 37 ℃, which is also called pseudoplastic flow, and is sticky due to entanglement and high viscosity of the temperature-sensitive hydrogel at low flow rate or at rest. However, when the flow velocity is increased, the relatively scattered chain-like particles are subjected to shear stress between flow layers, so that mutual hooking of the particles is reduced, rolling rotation occurs, and the particles are shrunk into a mass, and thus a shear thinning phenomenon is presented. Under the same shearing rate, the viscosity at 37 ℃ is always higher than that at 25 ℃, and the phenomenon that the viscosity of the temperature-sensitive hydrogel is obviously improved when the temperature is increased to be close to the body temperature (37 ℃) of a human body can also be seen from the phenomenon. The viscosity is suitable for the adhesion of the uterine cavity, and the support is provided for the temperature-sensitive hydrogel in the application of preventing the adhesion of the uterus.

3. Animal experiments

(1) Selecting experimental objects:

female rats 8 weeks old, weighing about 250g, sexually mature, were selected, acclimatized for one week, and operated in estrus (estrus cycle 4-5 days).

(2) The required materials are as follows:

reagent: normal saline, PBS buffer solution, 95% ethanol, 75% ethanol (or iodophor disinfection), 0.1% crystal violet solution, 10% sodium pentobarbital, 4% paraformaldehyde;

4% of paraformaldehyde: weighing 40g of paraformaldehyde powder, dissolving in 1000ml of Phosphate Buffer Solution (PBS), heating to 60 ℃, fully dissolving, cooling to normal temperature, sealing, and storing in shade for no more than 1 month.

Cleaning solution: 30% hydrochloric acid or 5% phenol aqueous solution for 24 hours, and then fully washing after being taken out. The method can be used for cleaning the cover glass or the glass slide.

(3) The group setting and processing mode is as follows:

randomly dividing 10 rats into 2 groups of 5 rats each; group 2 is a model group and a treatment group (temperature sensitive hydrogel group), respectively.

Model group: performing uterine curettage on two sides, and establishing a model of uterine cavity adhesion; 100 μ L of physiological saline was injected into both sides of the uterus.

Treatment groups: based on the established uterine cavity adhesion model, 100 mu L of temperature-sensitive hydrogel is injected into the uterus at two sides.

(4) Determining the estrus:

examination of exfoliated vaginal cells:

note: vaginal smear collection and oestrus cycle assessment 8:30-9:30 min, prevent cells to the next stage, and evaluate for at least one week.

Open the jaw of the left hand, insert the thumb and forefinger under the root of the rat tail, press the other three fingers and palm against the back half of the rat body, and pay attention to avoid applying too much force. The tail is lifted, the front claw of the tail is arranged on the squirrel cage, the hind limb is suspended, and the opening of the vaginal orifice can be seen. Sucking (50 μ L) physiological saline with a pipette and a pipette tip, placing the pipette tip at 3-5mm of the female mouse vaginal orifice, slowly releasing the liquid into the vagina, sucking back again, repeating for 4-5 times, dropping the liquid onto a glass slide, drying, fixing with 95% alcohol, staining with 0.1% crystal violet solution for 3min, washing, and observing under a microscope.

(5) Operation:

uterine curettage was used: shaving and disinfecting the abdomen, and anesthetizing and fixing.

The abdominal wall skin was cut longitudinally about 3cm above the pubic symphysis 2-3cm, the tissues were cut layer by layer into the abdominal cavity, and the Y-uterus of the rat was slowly picked up.

Bilateral simultaneous uterine horn surgery

The ophthalmology department is directly cut at the position about 5mm above the cervix uteri to make a longitudinal incision with the length of about 5mm, a homemade rat uterine cavity curettage is adopted to conduct uterine curettage through the incision above the cervix uteri, and the uterine curettage is stopped when the four walls of the uterine cavity are rough.

Thoroughly stopping bleeding with sterile gauze, suturing the uterus with 7-0 sutures intermittently, returning the uterus to the abdominal cavity, flushing the abdominal cavity with normal saline, closing the abdomen with 3-0 sutures, and injecting 200mg/kg of antibiotics every 48h after the operation.

Model group making longitudinal incisions of the same length only in the uterus

After the second estrus cycle, each is sacrificed, fixed in 4% paraformaldehyde for more than 24 hours, dehydrated in an ethanol gradient, then embedded in paraffin, and stained for sections.

(6) Result processing (detection):

1. the effect of uterine healing in each group was evaluated by a masson stain, hematoxylin-eosin (HE) stain on the uterus. The tissue morphology, masson, HE, intimal cells and endometrial thickness were examined.

(1) Morphology observation of rat uterus tissue:

fig. 2 is a tissue morphology diagram of rat uterus of a model group, and fig. 3 is a tissue morphology diagram of rat uterus of a treatment group. Firstly, the abdomens of two groups of rats are respectively disinfected and anesthetized for fixation. The abdominal wall skin is longitudinally incised about 3cm above the pubic symphysis, the tissues are incised layer by layer, the abdominal cavity is entered, and the Y-shaped uterus of the rat is slowly picked out. As shown in figures 2 and 3, the rats in the model group had significant abnormal hyperplasia of tissues on the left side of the uterus, while the rats in the treatment group had relatively flat and smooth uterus on the left side and had no significant hyperplasia. Compared with the uterine tissue shape of a model rat, the uterine tissue shape of the rat treated by the temperature-sensitive hydrogel is obviously improved, which shows that the temperature-sensitive hydrogel has obvious effect on the recovery of the uterine tissue shape of the rat.

(2) Uterine scar (MASSON):

two groups of rats are sacrificed after the second estrus cycle, fixed by 4% of poly methanol for more than 24 hours, dehydrated by using ethanol gradient, embedded in paraffin, sliced and dewaxed to distilled water; staining with Weigert iron hematoxylin staining solution for 3 minutes; alcohol differentiation is carried out for 15s (the differentiation time can be properly increased by the over-deep staining of the hematoxylin) by hydrochloric acid, and washing is carried out; returning the Masson bluing solution to blue, washing with water, and washing with distilled water for 1min; dyeing with ponceau fuchsin staining solution for 7-8s (controlling staining time according to tissue density), washing with 0.2% weak acid for 1min; washing with phosphomolybdic acid solution for 2min, washing with 0.2% weak acid for 1min; staining with aniline blue staining solution for 90s (controlling staining time according to tissue density), and washing with 0.2% weak acid for 1min; dehydrating with 95% ethanol for 3s, and dehydrating with anhydrous ethanol for 3 times, each time for 10s; the xylene is transparent for 3 times, each time for 2min, and sealed. The rat uterine scar is observed through MASSON staining, as shown in figures 4 and 5, white light scanning images of the left and right uterine scar (MASSON) of the rat in the model group are shown, and it can be obviously seen that the left and right uteruses of the rat in the model group are respectively obviously adhered; as shown in fig. 6 and 7, the white light scans of the left and right uterine scar (MASSON) of the rats in the treatment group show that the left and right uterine forms of the rats in the treatment group are normal and adhesion phenomenon does not occur, which indicates that the temperature-sensitive hydrogel has a significant effect on the adhesion of the uterus.

In addition, the pictures can also show that the optical density and the area of collagen fibers (blue) on the left side and the right side of a rat in a treatment group are obviously smaller than those of the uterus of a model group rat, and further show that the temperature-sensitive hydrogel has obvious effect on resisting fibrosis of the uterus of the rat.

(3) Endometrial cells (HE):

two groups of rats are sacrificed after the second estrus period respectively, fixed by 4 percent of poly-methanol for more than 24 hours, dehydrated by ethanol gradient, embedded in paraffin, sliced and dewaxed to distilled water, hematoxylin staining cell nucleus, sliced and Harris hematoxylin staining for 5min, washed by tap water, and then washed by 1 percent of hydrochloric acid alcohol for several seconds, washed by tap water, and then by 0.6 percent of ammonia water for returning blue, and washed by running water. Eosin staining of cytoplasm sections were stained in eosin stain for 3min. And (4) dehydrating and sealing the slices by gradient ethanol, taking the slices out of the xylene, slightly drying the slices, and sealing the slices by neutral gum.

The endometrial cells of the rats (chromatin in nuclei and nucleic acid in cytoplasm are bluish-colored; components in cytoplasm and extracellular matrix are reddened) were observed by HE staining, as shown in fig. 8, 9, 10, 11, and the left and right endometrial cells of the uterus of the model group rats were significantly reduced compared to the left and right endometrial cells of the uterus of the treated group rats; meanwhile, as can be seen from the picture, the area of the left and right uterine cavities of the rat in the model group is larger, and the area of the uterine cavity of the treatment group is smaller than that of the model group, which indicates that the recovery effect of the endometrium after treatment is better, and the basic shape of the uterine cavity is maintained without adhesion.

(4) Endometrial thickness:

observation of endometrial thickness by HE staining in rats (mean endometrial thickness = area/circumference, endometrial area and circumference were calculated using Image analysis software (Image Pro-Plus)) with results as shown in fig. 12, the endometrial thickness (Left uterus,977.75 μm) was significantly thicker in the Left side of rats in the treated group compared to the endometrial thickness (Left uterus,607.25 μm) in the Left side of rats in the model group; the endometrium thickness of the treated rat is remarkably thicker (Right uterus,954.75 μm) compared with that of the model rat (Right uterus,421 μm), which indicates that the temperature-sensitive hydrogel has remarkable effect on the recovery of the rat endometrium.

According to the tissue morphology of the uterus, the scar of the uterus, the endometrial cells and the thickness of the endometrium, the temperature-sensitive hydrogel has a good repairing effect on the damaged endometrium, and has obvious anti-fibrosis and anti-adhesion effects.

While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.

Claims

1. The temperature-sensitive hydrogel is characterized by comprising the following components in percentage by mass:

poloxamer 407:20 to 25 percent;

poloxamer 188:2.5 to 7.5 percent.

2. The temperature-sensitive hydrogel according to claim 1, wherein the solvent of the temperature-sensitive hydrogel is water.

3. The temperature-sensitive hydrogel according to claim 2, wherein the water comprises deionized water, water for injection, or physiological saline.

4. The temperature-sensitive hydrogel according to claim 2, wherein the solvent is replaced with phosphate buffer.

5. The temperature-sensitive hydrogel according to claim 1, wherein the mass fraction of poloxamer 407 is 20%, and the mass fraction of poloxamer 188 is 2.5%.

6. The temperature-sensitive hydrogel according to claim 5, wherein the temperature-sensitive hydrogel has a gelation temperature of 32-36 ℃.

7. The method for preparing a temperature-sensitive hydrogel according to any one of claims 1 to 6, comprising the steps of:

8. The method for preparing a temperature-sensitive hydrogel according to claim 7, wherein the certain temperature condition is 0 to 4 ℃.

9. The preparation method of the temperature-sensitive hydrogel according to claim 7, wherein the standing time is 20-24h.

10. Use of the temperature-sensitive hydrogel according to any one of claims 1 to 6 in the preparation of a product for preventing and treating uterine cavity adhesion, uterine fibrosis and promoting endometrial recovery.

11. A composite preparation comprising the temperature-sensitive hydrogel according to any one of claims 1 to 6.

12. Use of a complex formulation according to claim 11 for the preparation of a product for the repair of various lesions of the endometrium.

13. Use according to claim 12, characterized in that the repair of various lesions of the endometrium comprises the treatment of uterine cavity adhesion, uterine fibrosis and the promotion of endometrial recovery.

14. Use according to claim 13, characterized in that the mode of application is by means of in situ injection in the uterine cavity.