Medical gel separant and preparation method thereof

Abstract

The invention discloses a medical gel separant and a preparation method thereof, the medical gel separant comprises agarose gel particles and a solution of hyaluronic acid or its salt, and the agarose gel particles are uniformly distributed in the solution of hyaluronic acid or its salt. The product disclosed by the invention has the advantages of good biocompatibility, no side effects such as sensitization and the like, good flexibility and plasticity, smooth injection and convenience, easiness and safety in clinical use. A test of implanting I125 particles under the skin of a mouse finds that the product can effectively isolate radiation injury of built-in radioactive particles to the skin and organs of the mouse, can keep the original form for a long time, does not have obvious position deviation, and can be used for treating the mouse skin and organs. The method has a wide application prospect in the fields of stereotactic radiotherapy or radioactive particle local adjuvant therapy of prostatic cancer and the like.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and in particular relates to a medical gel isolating agent and a preparation method thereof. Background Art

[0002] Radiotherapy is one of the common strategies for tumor treatment. Its principle is to use radiation of different frequencies, which is the same as the vibration frequency of key atoms or atomic groups of DNA and RNA, thereby causing molecular changes, including base destruction or shedding, single-strand or double-strand breaks, hydrogen bond rupture, cross-linking in the helical structure, cross-linking between DNA molecules, and cross-linking between DNA and proteins, etc., so as to cause irreversible damage to cancer cells and achieve the purpose of treating cancer. For example, stereotactic body radiation therapy (SBRT) technology focuses radical radiation doses on the tumor site through external irradiation to achieve the purpose of eliminating and curing the tumor. However, radiotherapy may also cause unexpected radiation damage to adjacent healthy tissues. For example, late rectal reactions caused by prostate radiotherapy include symptoms such as frequent bowel movements, diarrhea, and fecal incontinence, which more or less affect the health and quality of life of patients during treatment.

[0003] In recent years, the use of "spacing" technology to reduce the risk of radiation damage to surrounding tissues during radiotherapy has gradually become the first choice for clinical applications. For example, products used in prostate cancer radiotherapy include intrarectal balloons PEG hydrogel Human collagen and cross-linked HA gel (NASHA gel ), etc., the common principle is to increase the space between the prostate and the rectal wall, thereby reducing the dose affecting the rectum and alleviating its toxic reaction. At present, hydrogel products are widely used. Due to the long radiotherapy time, the required gel should be able to maintain stability for a long time in the body, and be resistant to radiation degradation. In addition, it is necessary to maintain appropriate softness and easy injection, and to remain in the body for a long time without obvious positional displacement. These characteristics put forward extremely high performance requirements for gel products. CN 110917123 A discloses a hydrogel preparation with carboxymethyl chitosan as the main component, prepared by dissolving, extracting and other steps, which has good swelling and tensile properties, but the various organic reagents such as acetone and glutaraldehyde used in its preparation process have certain risks, and there are doubts about safety. CN107936272B discloses a 3D cross-linked sodium hyaluronate gel that is resistant to degradation, has high safety, and can be used for but not limited to tumor radiotherapy isolation and protection. In order to cross-link and prolong the degradation time in the body, a cross-linking agent needs to be added. In order to reduce the amount of cross-linking agent, it is necessary to improve the cross-linking efficiency through multi-step cross-linking reactions, and the process preparation process is relatively complicated.

[0004] Therefore, most existing gel release agents require the addition of organic reagents or cross-linking agents, which poses certain safety risks, and the preparation process is relatively complex and the production cost is high. Summary of the invention

[0005] In response to the problems existing in the prior art, the inventors discovered that agarose gel particles and hyaluronic acid or its salt solution have certain polymerization and shear viscosity after being mixed, and thus exhibit good cohesion. When used as an isolation gel, it can retain its original shape for a long time, is not prone to positional displacement, and can exert a good isolation and protection effect. In addition, the isolation gel does not use cross-linking agents and organic solvents during preparation, and is highly safe.

[0006] Agarose is a purified linear polysaccharide polymer isolated from large seaweed (such as red algae). Structurally, agarose is composed of D-galactose and 3,6-endo-L-galactose. It is hydrophilic, easy to shape and has certain mechanical properties. It can be dissolved in hot water in the form of a solution and becomes a gel when cooled to about 35°C. It is a polymer with special temperature responsiveness. Agarose is widely available, inexpensive, and has broad application prospects.

[0007] The invention provides a medical gel isolation agent containing agarose. Agarose gel particles are evenly dispersed in a hyaluronic acid or a salt solution thereof, so that the viscoelasticity and injection smoothness of the product can be improved. When the product is used for isolation and protection, it is not easy to be displaced, is resistant to radiation degradation, has high safety, and has a good isolation effect.

[0008] The present invention adopts the following technical solution:

[0009] A medical gel isolating agent comprises agarose gel particles and a solution of hyaluronic acid or its salt, wherein the agarose gel particles are uniformly distributed in the solution of hyaluronic acid or its salt.

[0010] Furthermore, the agarose gel particles are made of agarose powder as a raw material, and the agarose powder is dissolved, gelled, and granulated to obtain agarose gel particles. Dissolving refers to dissolving agarose powder in a solvent to form an agarose solution, gelling refers to controlling the temperature of the agarose solution to gel it, and granulating refers to crushing, sieving, and other treatments of the obtained agarose gel to obtain gel particles that meet the particle size requirements.

[0011] Further, the temperature of the agarose solution is controlled at ≤40°C for gelation, for example, 40°C, 39°C, 38°C, 37°C, 36°C, 35°C, 34°C, 33°C, 32°C, 31°C, 30°C, 29°C, 28°C, 27°C, 26°C, 25°C, 24°C, 23°C, 22°C, 21°C, 20°C, etc., and any range value therebetween.

[0012] Furthermore, the average particle size of the agarose gel particles in the medical gel separator is 100 to 800 μm, for example, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, 500 μm, 550 μm, 600 μm, 650 μm, 700 μm, 750 μm, and 800 μm.

[0013] Furthermore, the particle size of the agarose gel particles is detected by using a laser particle size analyzer. For example, a Winner 2308 laser particle size analyzer can be used to detect the particle size of the agarose gel particles.

[0014] Furthermore, the content of agarose compound in the medical gel isolation agent is 15-50 mg / mL, for example, 15 mg / mL, 18 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL.

[0015] Furthermore, the content of hyaluronic acid or its salt in the medical gel isolation agent is 1-10 mg / mL, for example, 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, etc.

[0016] Further, the hyaluronate is selected from one or more of sodium salt, potassium salt, zinc salt, calcium salt, magnesium salt and gold salt of hyaluronic acid. Various hyaluronates can wrap agarose particles like hyaluronic acid and have similar performances. Sodium hyaluronate is the most commonly used in the market, so sodium salt of hyaluronic acid is preferred.

[0017] Further, the molecular weight of hyaluronic acid or its salt is 100 kDa to 3000 kDa, for example, 100 kDa, 200 kDa, 300 kDa, 400 kDa, 500 kDa, 800 kDa, 1000 kDa, 1200 kDa, 1500 kDa, 1800 kDa, 2000 kDa, 2300 kDa, 2500 kDa, 2800 kDa, 3000 kDa, preferably 500 kDa to 2500 kDa.

[0018] Further, the solvent used for dissolving the agarose powder and the solution of hyaluronic acid or its salt are selected from one or more of water, physiological saline, phosphate buffer solution, phosphate-inorganic salt buffer solution, borate buffer solution, and borate-inorganic salt buffer solution. Among them, the main components of the phosphate buffer solution include one or more of Na2HPO4, NaH2PO4, KH2PO4, and K2HPO4, the main components of the phosphate-inorganic salt buffer solution include one or more of Na2HPO4, NaH2PO4, KH2PO4, K2HPO4, NaCl, KCl, and CaCl2, the main components of the borate buffer solution include H3BO3 and Na2B4O7, and the main components of the borate-inorganic salt buffer solution include one or more of H3BO3, Na2B4O7, and NaCl. The pH of the phosphate buffer solution and the borate buffer solution is preferably 5.5 to 7.5. Preferably, the solvent is physiological saline.

[0019] Furthermore, the medical gel release agent may also include a pH adjuster to adjust the pH of the medical gel release agent to 5.5-7.5, such as 5.5, 6.0, 6.5, 7.0, 7.5; preferably, the pH adjuster includes sodium hydroxide, potassium hydroxide, hydrochloric acid, phosphoric acid, etc.

[0020] The present invention also provides a method for preparing the above-mentioned medical gel release agent, which comprises the following steps:

[0021] (1) adding agarose powder to a solvent and heating to dissolve it to obtain solution A;

[0022] (2) dissolving hyaluronic acid or a salt thereof in a solvent to obtain a solution B;

[0023] (3) controlling the temperature to gel the solution A to obtain agarose gel;

[0024] (4) granulating the agarose gel prepared in step (3) to obtain agarose gel particles;

[0025] (5) The agarose gel particles are mixed evenly with solution B to obtain a medical gel isolating agent.

[0026] Furthermore, in step (1), the heating temperature is 80°C to 100°C, for example, 80°C, 85°C, 90°C, 95°C, 100°C.

[0027] Further, in step (1), the concentration of agarose in solution A is 16 to 55 mg / mL, for example 16 mg / mL, 18 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 52 mg / mL, 55 mg / mL, preferably 18 to 52 mg / mL.

[0028] Furthermore, in step (2), the concentration of hyaluronic acid or its salt in solution B is 8 to 55 mg / mL, for example 8 mg / mL, 10 mg / mL, 16 mg / mL, 18 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 52 mg / mL, 55 mg / mL, preferably 10 to 52 mg / mL.

[0029] Furthermore, in steps (1) and (2), the solvent includes one or more of water, physiological saline, phosphate buffer solution, phosphate-inorganic salt buffer solution, borate buffer solution, borate-inorganic salt buffer solution, preferably physiological saline.

[0030] Furthermore, in step (3), the gelation temperature is ≤40°C.

[0031] Furthermore, in step (4), the agarose gel is granulated through a sieve to obtain agarose gel particles, the mesh size of the sieve is 20 to 100 meshes, and the average particle size of the agarose particles is 100 to 800 μm.

[0032] Furthermore, if necessary, the method further comprises a step of adjusting the pH of the obtained medical gel isolation agent to maintain the pH at 5.5 to 7.5.

[0033] Furthermore, the molecular weight of hyaluronic acid and the definition of hyaluronate are consistent with those described above.

[0034] The present invention proposes for the first time to prepare a medical gel isolation agent using agarose and hyaluronic acid or its salt as effective ingredients. The hydrogel isolation agent has good biocompatibility, no side effects such as sensitization, and also has good flexibility and high injection smoothness, ensuring the convenience and safety of clinical use. 125The particle test confirmed that the product of the present invention can effectively isolate the radiation damage of the built-in radioactive particles to the mouse skin and organs, and can retain its original shape for a long time without obvious position shift. It can be seen that the product of the present invention is safe, stable and reliable, can effectively isolate radiation, has good cohesion, good viscoelasticity, is not easy to move, and is resistant to radiation degradation. It can be used in the field of clinical medicine and has broad application prospects in the fields of stereotactic radiotherapy of prostate cancer or local adjuvant therapy of radioactive particles.

[0035] Furthermore, the present invention also provides the use of the above-mentioned medical gel isolation agent in the preparation of an isolation agent for radiotherapy or local auxiliary therapy with radioactive particles.

[0036] The present invention provides a medical gel isolation agent, which comprises firstly gelling and granulating agarose, and then mixing it with hyaluronic acid or its salt solution to obtain the medical gel isolation agent. The present invention has the following advantages:

[0037] 1. The present invention compounded agarose gel and hyaluronic acid or its salt solution as a radiotherapy protective isolation agent. The hyaluronic acid or its salt solution can wrap the granular agarose gel, change the physical properties of the agarose gel, and ensure the smoothness of the injection. The addition of hyaluronic acid or its salt solution improves the problem of agarose gel being hard and difficult to inject, and by adjusting the ratio of the two, the hydrogel isolation agent has good plasticity and mechanical properties, and can be smoothly injected.

[0038] 2. In the present invention, agarose is first gelled and granulated and then mixed with hyaluronic acid or its salt solution. Compared with directly mixing agarose and hyaluronic acid or its salt to form a gel together, the obtained hydrogel isolation agent has better viscoelasticity and cohesion, can retain the original shape for a longer time, is not easy to move, and has a more significant effect of isolating radioactive particles.

[0039] 3. Subcutaneous implantation of I 125 Particle experiments found that the medical gel isolation agent prepared by the present invention can effectively isolate the radiation damage of radioactive particles to the skin and organs of mice, and can retain its original shape for a long time without obvious position shift. It can be applied in the field of clinical medicine, such as stereotactic radiotherapy of prostate cancer or local adjuvant therapy of radioactive particles, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 The following are the appearance characteristics of the products prepared in Example 1 and Comparative Examples 1-4.

[0041] Specific implementation methods

[0042] The embodiments of the present invention will be described in detail below in conjunction with examples and drawings. The following examples are only used to illustrate the present invention, and those skilled in the art will understand that they should not be regarded as limiting the scope of the present invention.

[0043] Unless otherwise specified, all reagents used in the following examples and comparative examples are commercially available products.

[0044] Example 1

[0045] To prepare the medical gel isolation agent, the steps are as follows:

[0046] (1) Weigh 30 g of dry agarose powder, dissolve it in 900 mL of physiological saline, heat it to 80°C to 90°C, and stir to dissolve, to obtain solution A;

[0047] (2) Weigh 1.0 g of sodium hyaluronate (molecular weight 2250 kDa), dissolve it in 100 mL of normal saline, and stir to dissolve at room temperature to prepare solution B;

[0048] (3) placing solution A at 30°C to 35°C to gelate, then placing it in a stirring container and breaking it into blocks;

[0049] (4) granulating the gel block prepared in step (3) through a 60-mesh sieve to obtain agarose gel particles with an average particle size of 450 to 550 μm;

[0050] (5) The agarose gel particles were mixed with solution B, the temperature was controlled at 35° C., the rotation speed was maintained at about 45 rpm, and after stirring for 30 min, the pH value was adjusted to about 7.0 to obtain a medical gel isolation agent.

[0051] (6) The medical gel isolation agent is filled into a disposable sterile syringe and sterilized by irradiation with gamma rays (dose 15 kGy).

[0052] The obtained medical gel isolating agent contains 30 mg / ml agarose and 1 mg / ml sodium hyaluronate.

[0053] Example 2

[0054] The medical gel isolating agent was prepared according to the method of Example 1, except that in step (1), the amount of agarose powder added was 18 g. The agarose content in the obtained medical gel isolating agent was 18 mg / ml, and the sodium hyaluronate content was 1 mg / ml.

[0055] Example 3

[0056] A medical gel isolating agent was prepared according to the method of Example 1, except that: in step (1), the amount of agarose powder added was 25 g; in step (2), the amount of sodium hyaluronate added was 3 g. The agarose content of the obtained medical gel isolating agent was 25 mg / ml, and the sodium hyaluronate content was 3 mg / ml.

[0057] Example 4

[0058] A medical gel isolating agent was prepared according to the method of Example 1, except that: in step (1), the amount of agarose powder added was 20 g; in step (2), the amount of sodium hyaluronate added was 5 g. The agarose content of the obtained medical gel isolating agent was 20 mg / ml, and the sodium hyaluronate content was 5 mg / ml.

[0059] Example 5

[0060] A medical gel isolating agent was prepared according to the method of Example 1, except that: in step (1), the amount of agarose powder added was 45 g; in step (2), the amount of sodium hyaluronate added was 1 g. The agarose content of the obtained medical gel isolating agent was 45 mg / ml, and the sodium hyaluronate content was 1 mg / ml.

[0061] Example 6

[0062] The medical gel release agent was prepared according to the method of Example 1, except that in step (4), the mesh size of the sieve used for granulation was 30 meshes, and the average particle size of the agarose gel particles was 600-750 μm. The agarose content of the obtained medical gel release agent was 30 mg / ml, and the sodium hyaluronate content was 1 mg / ml.

[0063] Example 7

[0064] The medical gel release agent was prepared according to the method of Example 1, except that in step (4), the mesh size of the sieve used for granulation was 80 mesh, and the average particle size of the agarose gel particles was 250-450 μm. The agarose content of the obtained medical gel release agent was 30 mg / ml, and the sodium hyaluronate content was 1 mg / ml.

[0065] Example 8

[0066] A medical gel isolating agent was prepared according to the method of Example 1, except that in step (2), the molecular weight of sodium hyaluronate was 1000 kDa.

[0067] Example 9

[0068] A medical gel isolating agent was prepared according to the method of Example 1, except that in step (2), the molecular weight of sodium hyaluronate was 500 kDa.

[0069] Comparative Example 1

[0070] The medical gel isolating agent was prepared according to the method of Example 1, except that in step (2), no sodium hyaluronate was added, and only 100 mL of physiological saline was used as solution B. The agarose content in the obtained medical gel isolating agent was 30 mg / ml.

[0071] Comparative Example 2

[0072] The medical gel isolating agent was prepared according to the method of Example 1, except that the amount of agarose powder added was 5 g. The agarose content in the obtained medical gel isolating agent was 5 mg / ml, and the sodium hyaluronate content was 1 mg / ml.

[0073] Comparative Example 3

[0074] (1) Weigh 30 g of sodium hyaluronate (molecular weight 2250 kDa), dissolve it in 900 mL of normal saline, stir evenly, and obtain gel A after sufficient swelling;

[0075] (2) Prepare 100 mL of normal saline as solution B;

[0076] (3) granulating gel A through a 60-mesh sieve to obtain hyaluronic acid gel particles with an average particle size of 450 to 550 μm;

[0077] (4) The hyaluronic acid gel particles were mixed with solution B, the temperature was controlled at 35° C., the rotation speed was maintained at about 45 rpm, and after stirring for 30 min, the pH value was adjusted to about 7.0 to obtain a medical gel isolation agent.

[0078] (5) The medical gel isolation agent is filled into a disposable sterile syringe and sterilized by irradiation with gamma rays (dose 15 kGy).

[0079] The content of sodium hyaluronate in the obtained medical gel isolation agent is 30 mg / ml.

[0080] Comparative Example 4

[0081] (1) Weigh 30 g of dry agarose powder and 1.0 g of sodium hyaluronate (molecular weight 2250 kDa), dissolve the agarose powder and sodium hyaluronate in 900 mL of normal saline, heat to 80° C. to 90° C., stir to dissolve, and obtain a mixed solution. Use NaOH solution to adjust the pH value to about 7.0;

[0082] (2) placing the mixed solution at 30° C. to 35° C. to gel, then placing it in a stirring container and breaking it into blocks;

[0083] (3) granulating the gel block prepared in step (3) through a 60-mesh sieve to obtain gel particles with an average particle size of 450 to 550 μm;

[0084] (4) The gel particles were mixed with 100 ml of physiological saline, the temperature was controlled at 35° C., the rotation speed was maintained at about 45 rpm, and after stirring for 30 min, the pH value was adjusted to about 7.0 to obtain a medical gel isolation agent.

[0085] (5) The medical gel isolation agent is filled into a disposable sterile syringe and sterilized by irradiation with gamma rays (dose 15 kGy).

[0086] The obtained medical gel isolating agent contains 30 mg / ml agarose and 1 mg / ml sodium hyaluronate.

[0087] Test Example 1 Polymerization Performance Test

[0088] The medical gel release agent prepared in each embodiment and comparative example was slowly pushed out from the syringe to observe the polymerization state of the sample:

[0089] 1) If the sample is smooth and aggregated after being pushed out, and is not easy to disperse after being kneaded and has a certain viscosity, it indicates that the sample has good aggregation;

[0090] 2) If the sample is not smooth after being pushed out, is easy to disperse after rubbing, feels gritty, or appears hydrated, it indicates that the sample has poor polymerization properties.

[0091] The specific test results are shown in Table 1.

[0092] Table 1

[0093]

[0094]

[0095] Test Example 2 Shear Viscosity

[0096] The shear viscosity of the gel release agent prepared in each embodiment and comparative example was evaluated by using a ThermoFisher rotational rheometer at a shear rate of 0.25 Hz (25±0.1° C.). The specific test results are shown in Table 2.

[0097] Table 2

[0098] Shear viscosity (Pa·S) Example 1 1247 Example 2 1071 Example 3 1142 Example 4 1025 Example 5 963 Example 6 1195 Example 7 1053 Example 8 1083 Example 9 1001 Comparative Example 1 518 Comparative Example 2 234 Comparative Example 3 21 Comparative Example 4 647

[0099] Test Example 3 In vitro degradation test

[0100] The degradation time simulation test was carried out using the gel isolation agent prepared in Example 1 and Comparative Examples 1-4. 0.8 g of each sample was accurately weighed and placed in a test tube. 2 mL of normal saline was added. After mixing with a vortex mixer, 2 mL of bacterial hyaluronidase solution was added to make the enzyme concentration in the final enzymatic solution 220 IU / mL. After oscillation and mixing, it was immediately placed in a 37°C water bath. 50 ul of the sample enzymatic solution was drawn at 30 min, 60 min, 90 min, and 120 min, respectively, and added to 4 mL of normal saline. The sample was oscillated and mixed, and the absorbance of the sample at 232 nm was measured by a UV-visible spectrophotometer, and the normal saline was used as a blank control. The degradation rate of the sample in the test sample was calculated according to the measured absorbance.

[0101] Determination of degradation endpoint: If the difference in absorbance between adjacent time points does not exceed 0.01, it is considered that the degradation endpoint has been reached at the previous time point.

[0102] Calculation: Degradation rate (%) = M / C × 100%

[0103] M: absorbance of the test sample;

[0104] C: absorbance at the degradation endpoint.

[0105] Table 3

[0106]

[0107] It can be seen from Table 3 that the degradation rate of the sample in Example 1 at different time periods is significantly lower than that in Comparative Examples 1-4, indicating that the isolation gel prepared by the present invention has a better degradation resistance effect.

[0108] Test Example 4: Isolation Effect Test

[0109] The gel isolation agent prepared in Example 1 and Comparative Examples 1-4 was used to test the isolation effect. According to the requirements for clinical use samples, each sample was prepared in a 100,000-class clean workshop. Each sample was equipped with a 30G×1 / 2 (0.3mm×13mm) sterile needle and a booster plate, and the filling volume was 1.0mL.

[0110] The KM mice used in the experiment were purchased from the Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences, SPF grade. During the experiment, sufficient food and water were ensured and they were fed in a constant temperature and humidity breeding room. 42 KM mice of similar age and weight were selected and activated mouse breast cancer tumor cell culture medium (cell density 6×10 7 / mL), 0.1mL of cell stock solution was inoculated in the center of the back, and the tumor size was screened to be 0.8-1.2cm after one week. 3 The mice were used as test subjects. The screened mice were divided into a blank group, a control group, an example 1 group, and comparative examples 1-4 groups, with 6 mice in each group. The treatment of each group of mice is shown in Table 4.

[0111] Table 4

[0112]

[0113]

[0114] The mice in the control group, Example 1 group and Comparative Examples 1-4 groups were anesthetized with 40 mg / kg sodium pentobarbital and injected with an 18G syringe. 125 I particles were implanted in the center of the dorsal tumor, 2 particles were implanted in each mouse 125 I particles. A 30G injection needle was used to subcutaneously implant 1.0 mL of the gel isolation agent prepared in Example 1 and Comparative Examples 1-4 around the tumor of mice in Example 1 and Comparative Examples 1-4, respectively. During the injection, three injections were performed around the tumor tissue to form a ring-shaped package. After the treatment, the mice were placed in a unified feeding room for feeding, and the feeding conditions were kept consistent during the period. At the same time, the mice after the particles were implanted were separated by more than 3 m to prevent mutual interference of the radiation effects of the particles. During the test, the mice in the blank group were used as a reference to verify whether the feeding environment, feeding, etc. during the observation period had an adverse effect on the test. After 72 days of continuous irradiation, a radiation dosimeter (ATOMTEX AT1123) was used to measure the surface radiation dose of the mice in the control group, the example group and the comparative example group.

[0115] During the experiment, the growth of mice in the blank group was normal, indicating that the feeding, feeding environment and other factors during the experiment did not affect the normal progress of the experiment. After the experiment, the skin damage on the surface of the mice in the control group was the most serious, followed by the comparative examples 1-4 groups, and the surface skin damage on the mice in the embodiment 1 group was the lightest, and the position of the isolating agent in the embodiment 1 group did not shift significantly, while the comparative examples 1-4 groups shifted significantly.

[0116] After 72 days of the experiment, the surface radiation doses of mice in each group are shown in Table 5 below. The results show that the surface radiation doses of mice in Example 1 group were significantly lower than those in Comparative Example 1-4 groups and the control group, indicating that implantation of the gel isolation agent of the present invention does play a role in isolating radioactive particle rays.

[0117] Table 5

[0118]

[0119]

[0120] The above embodiments are preferred implementation modes of the present invention, but the present invention is not limited by the embodiments. Any other changes, substitutions and simplifications made without departing from the essence and principles of the present invention shall be considered as equivalent replacement modes and shall be included in the protection scope of the present invention.

Claims

1. A medical gel release agent, characterized in that: The invention comprises agarose gel particles and a solution of hyaluronic acid or its salt, wherein the agarose gel particles are uniformly distributed in the solution of hyaluronic acid or its salt.

2. The medical gel release agent according to claim 1, characterized in that: The agarose gel particles are obtained by dissolving, gelling and granulating agarose powder.

3. The medical gel release agent according to claim 1 or 2, characterized in that: The average particle size of agarose gel particles is 100 to 800 μm.

4. The medical gel release agent according to claim 1 or 2, characterized in that: The solvents used to prepare the solution of agarose gel particles and hyaluronic acid or its salt are selected from one or more of water, physiological saline, phosphate buffer solution, phosphate-inorganic salt buffer solution, borate buffer solution, and borate-inorganic salt buffer solution.

5. The medical gel release agent according to claim 1 or 2, characterized in that: The content of agarose in the gel isolation agent is 15-50 mg / mL, and the content of hyaluronic acid or its salt is 1-10 mg / mL.

6. The medical gel release agent according to claim 1 or 2, characterized in that: The molecular weight of the hyaluronic acid or its salt is 100 kDa to 3000 kDa, preferably 500 kDa to 2500 kDa; Preferably, the hyaluronate is selected from one or more of sodium salt, potassium salt, zinc salt, calcium salt, magnesium salt and gold salt of hyaluronic acid, preferably sodium salt of hyaluronic acid.

7. The medical gel release agent according to any one of claims 1 to 6, characterized in that: The invention also comprises a pH adjusting agent for adjusting the pH of the medical gel isolation agent to 5.5-7.

5.

8. A method for preparing the medical gel release agent according to any one of claims 1 to 6, characterized in that The following steps are involved: (1) adding agarose powder to a solvent and heating to dissolve it to obtain solution A; (2) dissolving hyaluronic acid or a salt thereof in a solvent to obtain a solution B; (3) controlling the temperature to gel the solution A to obtain agarose gel; (4) granulating the agarose gel prepared in step (3) to obtain agarose gel particles; (5) The agarose gel particles are mixed evenly with solution B to obtain a medical gel isolating agent.

9. The preparation method according to claim 8, characterized in that: The method comprises at least one of the following conditions: condition 2, in step (1), the concentration of agarose in solution A is 16 to 55 mg / mL; Condition 3: In step (1), the heating temperature is 80°C to 100°C; Condition 4: In step (2), the concentration of hyaluronic acid or its salt in solution B is 8 to 55 mg / mL; Condition 5: In step (3), the gelation temperature is ≤40°C.

10. The preparation method according to claim 8 or 9, characterized in that: After step (5), the method further includes adding a pH regulator to adjust the pH of the system to 5.5 to 7.5.

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