Smeglutide-containing NPs hydrogel and preparation method thereof

Abstract

The invention discloses a semeglutide-containing NPs hydrogel and a preparation method thereof, and relates to the technical field of polymer composites.The semeglutide-containing NPs hydrogel comprises a main drug, polylactic acid nanoparticles, dodecyl modified hydroxypropyl methyl cellulose and PBS; wherein the polylactic acid nanoparticles are prepared by wrapping graphene with polyethylene glycol-polylactic acid, the main drug is semeglutide, and the concentration of the semeglutide in the hydrogel is 2-20 mg / ml. The polylactic acid nano-particles and the dodecyl modified hydroxypropyl methyl cellulose comprise the following components in percentage by weight: 1-2wt% of the dodecyl modified hydroxypropyl methyl cellulose and 10wt% of the polylactic acid nano-particles; the long-term sustained and controlled release effect can be realized; and the degradation speed of the nanoparticles coated with the graphene oxide is inconsistent with that of the nanoparticles not coated with the graphene oxide, so that the release speed of the medicine can be further controlled.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer composite materials, and in particular to a NPs hydrogel containing semaglutide and a preparation method thereof. Background Art

[0002] Gel is a material with a three-dimensional spatial network structure. It is widely used in people's production and life, especially in the fields of bioengineering and medicine. This material is usually a three-dimensional polymer network formed by polymer chains. It can absorb and retain a large amount of water or biological fluids, but it is insoluble in water due to physical and chemical cross-linking. Hydrogel materials formed by hydrophilic polymers show thermodynamic compatibility when they come into contact with water, that is, they can swell in aqueous media. They have been widely used in the fields of drug controlled release, sensors, tissue engineering, etc.

[0003] Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has 94% sequence homology with human GLP-1. It regulates blood sugar levels by activating the GLP-1 receptor, promoting insulin secretion and inhibiting glucagon secretion in a glucose concentration-dependent manner. At the same time, semaglutide can also delay gastric emptying, increase satiety, reduce appetite and energy intake, thereby achieving the effect of weight loss.

[0004] For example, a composite drug-loaded gel and its preparation method in Chinese patent application number CN202110331349.3, the preparation method includes the steps of: S1, adding pyrrole and dopamine hydrochloride to water and mixing them evenly, then adding ammonium persulfate, stirring the reaction, and centrifuging and washing to obtain a polypyrrole-polydopamine nanocomposite material; S2, placing the nanocomposite material in a 1mol / L hydrochloric acid solution containing drug molecules and a graphene oxide aqueous solution in turn, and centrifuging to obtain a graphene oxide-polypyrrole-polydopamine nanocomposite drug-loaded material; S3, mixing the nanocomposite drug-loaded material with a water-soluble polymer solution, adding a calcium chloride solution, stirring and standing to obtain the composite drug-loaded gel. The composite drug-loaded material provided by the invention is compounded with a water-soluble polymer, which can promote the formation of the composite drug-loaded gel and slow down the burst release phenomenon in the early stage of drug release. At the same time, the composite drug-loaded gel has multiple stimulus responsiveness.

[0005] However, for diabetic patients, its long-term sustained-release effect still needs to be improved. Summary of the invention

[0006] The embodiments of the present application provide a NPs hydrogel containing semaglutide and a preparation method thereof, thereby solving the problems of insufficient compliance of diabetic patients and insufficient drug sustained-release capacity in the prior art and achieving a longer sustained-release time.

[0007] The embodiment of the present application provides a NPs hydrogel containing semaglutide, comprising a main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, and PBS; wherein the polylactic acid nanoparticles are prepared by polyethylene glycol-polylactic acid encapsulated graphene.

[0008] Furthermore, the main drug is semaglutide, and the concentration of semaglutide in the hydrogel is 2-20 mg / ml.

[0009] Furthermore, the weight percentage of the polylactic acid nanoparticles and the dodecyl-modified hydroxypropyl methylcellulose is 1-2 wt % of the dodecyl-modified hydroxypropyl methylcellulose and 10 wt % of the polylactic acid nanoparticles.

[0010] Furthermore, in the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10wt%.

[0011] The above-mentioned method for preparing NPs hydrogel containing semaglutide specifically comprises: S1, dispersing graphene oxide powder in DMF or PBS, and making it uniformly dispersed by ultrasonic treatment;

[0012] S2. Under the protection of inert gas, polyethylene glycol, L-lactide and the catalyst are uniformly mixed; at the same time, the dispersed graphene oxide solution is slowly added to the copolymer reaction system while stirring;

[0013] The mass ratio of polyethylene glycol to L-lactide is 1:(2-9);

[0014] S3, heating the reaction system to 110-130°C, stirring the reaction for 16-24h, polymerizing the polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and in the process wrapping the graphene oxide inside the copolymer; dissolving the polyethylene glycol-polylactic acid block copolymer in DMSO, and dripping it into water under high-speed stirring to form a nanoparticle suspension; centrifuging and purifying, and resuspending in PBS to obtain a nanoparticle solution;

[0015] S4, mixing the semaglutide solution with the nanoparticle solution, encapsulating the semaglutide into the nanoparticles, and using graphene oxide to adsorb the semaglutide; filtering out the nanoparticles

[0016] S5. Prepare a 1-2 wt % dodecyl-modified hydroxypropyl methylcellulose solution; when in use, add nanoparticles to the dodecyl-modified hydroxypropyl methylcellulose solution and stir evenly to obtain NPs hydrogel containing semaglutide.

[0017] Furthermore, the nanoparticle hydrogel is administered via subcutaneous injection, and the dosage is adjusted according to the condition of the disease.

[0018] Furthermore, the particle size of the nanoparticles is 30-200 nm; the single-layer diameter of the graphene oxide used is no more than 200 nm; and the oxygen content is 30%.

[0019] When further filtering and screening the nanoparticles, particles with a particle size greater than 200nm are screened for the second time to screen out large nanoparticles of 200-300nm and mix them with the screened nanoparticles. The nanoparticles screened for the second time are large nanoparticles, and the nanoparticles screened for the first time are small nanoparticles. The mass ratio of large nanoparticles to small nanoparticles is 1:14.

[0020] Furthermore, after unwrapped graphene oxide was loaded with semaglutide in the same way as the nanoparticles, it was directly mixed into dodecyl-modified hydroxypropyl methylcellulose;

[0021] The particle size of graphene oxide is less than 200 nm; the mass ratio of unwrapped graphene oxide to wrapped graphene oxide is 1:9.

[0022] Furthermore, the graphene oxide is also roughened, including heavy roughening, medium roughening, and light roughening;

[0023] The specific method of heavy roughening is: chemical etching with 95% sulfuric acid, the reaction time is 0.5-1h;

[0024] Medium roughening is specifically: chemical etching is performed using 75% sulfuric acid with a reaction time of 0.5-1h;

[0025] Light roughening is as follows: using 20kHz ultrasonic treatment 0.5-1;

[0026] The wrapped graphene oxide was combined with unwrapped graphene oxide using different roughening treatments.

[0027] One or more technical solutions provided in the embodiments of the present application have at least the following technical effects or advantages:

[0028] First, graphene oxide has a large specific surface area and rich oxygen-containing functional groups, which can effectively adsorb semaglutide molecules and fix them in nanoparticles, thereby slowing down the release rate of semaglutide and achieving a sustained and controlled release effect; and increasing the loading capacity of nanoparticles for drugs to prevent the initial burst release from causing large changes in drug concentration in the body; as part of the nanoparticles, graphene oxide enhances the structural stability of the hydrogel, and its lamellar structure and good dispersibility form a more dense and stable hydrogel network, which increases the retention time of the hydrogel in the human body; graphene oxide has good biocompatibility and degradability, which makes the hydrogel containing it safer and more sustainable in the human body. Over time, graphene oxide will gradually degrade, while releasing semaglutide, achieving a long-term sustained and controlled release effect; and the degradation rate of nanoparticles wrapped with graphene oxide is inconsistent with that of nanoparticles not wrapped with graphene oxide, so that the release rate of the drug can be further controlled.

[0029] Second, since large nanoparticles have a relatively small specific surface area due to their large particle size, the rate at which drugs are released from the particles will be relatively slow, while small nanoparticles, on the contrary, will release drugs relatively quickly. Therefore, the mixed use of nanoparticles of different particle sizes can achieve a dual release mechanism of drugs, that is, a combination of rapid release and slow release; Encapsulated graphene oxide nanoparticles: These particles are encapsulated by polyethylene glycol-polylactic acid and have a relatively large particle size, forming a relatively stable skeleton structure in the hydrogel, and the release of drugs is relatively slow, which is conducive to achieving long-term sustained release;

[0030] Third, since the particle size of unwrapped graphene oxide is less than 200 nm, the graphene oxide particles directly loaded with semaglutide can release the drug faster, provide an initial drug concentration peak, and quickly reach the desired drug concentration, making the initial in vivo drug concentration controllable, and then the wrapped nanoparticles maintain a lower but stable drug concentration.

[0031] Fourth, heavy roughening treatment can significantly increase the drug loading capacity because the high specific surface area provides more binding sites. However, it can also easily lead to an increase in the initial release of the drug because surface defects and roughness may accelerate the dissolution and release of the drug. Medium roughening: while increasing the drug loading capacity, it controls the drug release rate relatively smoothly. Medium roughening treatment is more suitable for drug delivery systems that require a medium release rate. Light roughening: mainly increases the surface roughness through physical vibration, which helps the uniform adsorption and sustained release of the drug. The roughening treatment of graphite oxide wrapped by nanoparticles affects the sustained and controlled release process of the entire hydrogel, while the unwrapped ones only affect the early release. DETAILED DESCRIPTION

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by technicians in the technical field to which the present invention belongs; the terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention; the term "and / or" used herein includes any and all combinations of one or more related listed items.

[0033] Embodiment 1

[0034] The present application discloses a NPs hydrogel containing semaglutide, which specifically comprises: a main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose, and PBS; wherein the polylactic acid nanoparticles are prepared by polyethylene glycol-polylactic acid encapsulated graphene;

[0035] The main drug is semaglutide, and the concentration of semaglutide in the hydrogel is 2-20 mg / ml;

[0036] The polylactic acid nanoparticles and the dodecyl-modified hydroxypropyl methylcellulose are 1-2 wt % of dodecyl-modified hydroxypropyl methylcellulose and 10 wt % of the polylactic acid nanoparticles;

[0037] In the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10wt%;

[0038] The preparation method of the above-mentioned semaglutide NPs hydrogel is:

[0039] S1, dispersing graphene oxide powder in DMF or PBS, and making it uniformly dispersed by ultrasonic treatment;

[0040] S2. Under the protection of inert gas, polyethylene glycol, L-lactide and the catalyst are uniformly mixed; at the same time, the dispersed graphene oxide solution is slowly added to the copolymer reaction system while stirring;

[0041] The mass ratio of polyethylene glycol to L-lactide is 1:(2-9);

[0042] S3, heating the reaction system to 110-130°C, stirring the reaction for 16-24h, polymerizing the polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and in the process wrapping the graphene oxide inside the copolymer; dissolving the polyethylene glycol-polylactic acid block copolymer in DMSO, and dripping it into water under high-speed stirring to form a nanoparticle suspension; centrifuging and purifying, and resuspending in PBS to obtain a nanoparticle solution;

[0043] The particle size of the nanoparticles after filtration is 30-200nm; the single-layer diameter of the graphene oxide used is no more than 200nm; the oxygen content is 30%;

[0044] S4, mixing the semaglutide solution with the nanoparticle solution, encapsulating the semaglutide into the nanoparticles, and using graphene oxide to adsorb the semaglutide; filtering out the nanoparticles

[0045] S5. Prepare a 1-2 wt % dodecyl-modified hydroxypropyl methylcellulose solution; when in use, add nanoparticles to the dodecyl-modified hydroxypropyl methylcellulose solution and stir evenly to obtain NPs hydrogel containing semaglutide.

[0046] The nanoparticle hydrogel is administered via subcutaneous injection, and the dosage is adjusted according to the condition;

[0047] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages:

[0048] Graphene oxide has a large specific surface area and abundant oxygen-containing functional groups, and can effectively adsorb semaglutide molecules, thereby fixing them in nanoparticles, thereby slowing down the release rate of semaglutide and achieving a sustained-release effect; and increasing the loading amount of the nanoparticles for the drug, preventing the initial burst release from causing large changes in the drug concentration in the body; as part of the nanoparticles, graphene oxide enhances the structural stability of the hydrogel, and its lamellar structure and good dispersibility form a more dense and stable hydrogel network, thereby increasing the retention time of the hydrogel in the human body;

[0049] Graphene oxide has good biocompatibility and degradability, which makes the hydrogel containing it safer and more sustainable in the human body. Over time, graphene oxide will gradually degrade and release semaglutide, achieving a long-term sustained-release effect; and the degradation rate of nanoparticles wrapped with graphene oxide is inconsistent with that of nanoparticles not wrapped with graphene oxide, so the release rate of the drug can be further controlled;

[0050] Due to the reinforcing effect of graphene oxide, the retention time of the hydrogel in the human body is significantly extended, ensuring that semaglutide can be continuously released at the target site and improving the therapeutic effect; the adsorption effect of graphene oxide enables semaglutide to be released from the hydrogel in a slower and more controllable manner, maintaining a stable concentration of the drug in the body, reducing side effects, and improving patient compliance; by extending the retention time and achieving a sustained-controlled release effect, the hydrogel containing graphene oxide can improve the bioavailability of semaglutide. Due to the longer retention time, the realization of a sustained-controlled release effect, and the improved bioavailability, the semaglutide NPs hydrogel containing graphene oxide can significantly improve the therapeutic effect;

[0051] The sustained-release effect helps to reduce the peak concentration and fluctuation of the drug, thereby reducing the incidence and severity of side effects; because the drug release is more stable and lasts longer, patients can receive treatment more conveniently and improve compliance.

[0052] In some embodiments, when polyethylene glycol: L-lactide = 1:2, the content of L-LA in the polylactic acid nanoparticles is relatively high, resulting in a higher degradation rate of the nanoparticles; short-term drug delivery is used in the treatment of diseases that require rapid onset but do not want to continue to administer the drug for too long, such as acute conditions or short-term management;

[0053] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 48 hours was 32%; the cumulative release after 14 days was 68%;

[0054] In some embodiments, polyethylene glycol: L-lactide = 1:5, which can balance the release rate and duration of the drug; can stably release the drug over a long period of time, reduce the frequency of administration, and improve patient compliance;

[0055] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 48 hours was 28%; the cumulative release after 14 days was 58%;

[0056] In some embodiments, polyethylene glycol: L-lactide = 1:9; suitable for long-term administration to ensure stable release of the drug over a long period of time;

[0057] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 48 hours is 24%; the cumulative release after 14 days is 53%.

[0058] Embodiment 2

[0059] The above embodiment further improves on the basis of the first embodiment by adding graphene oxide to the hydrogel to increase the stability of the hydrogel and reduce the early burst release, in order to increase the loading amount of the nanoparticles for the drug and reduce the direct effect of the free drug.

[0060] When filtering and screening nanoparticles, particles with a particle size greater than 200nm are also screened for the second time to screen out large nanoparticles of 200-300nm and mix them with the screened nanoparticles. The nanoparticles screened for the second time are large nanoparticles, and the nanoparticles screened for the first time are small nanoparticles. The mass ratio of large nanoparticles to small nanoparticles is 1:14.

[0061] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages:

[0062] Large nanoparticles have a relatively small specific surface area due to their large particle size, so the rate at which drugs are released from the particles is relatively slow. On the contrary, small nanoparticles have a relatively fast drug release rate. Therefore, mixing nanoparticles of different particle sizes can achieve a dual drug release mechanism, that is, a combination of fast release and slow release.

[0063] The distribution and arrangement of large and small nanoparticles in hydrogels are different, which will affect the overall structure and stability of the hydrogel. Large particles form a more stable skeleton structure, while small particles may fill in the gaps between large particles, thereby enhancing the density and stability of the hydrogel and also helping to regulate the release rate of drugs;

[0064] Due to the mixed use of large and small nanoparticles, the retention time of the hydrogel in the human body may be prolonged. The stable skeleton formed by the large particles and the filling effect of the small particles jointly enhance the structural stability of the hydrogel, making it more difficult to be cleared by the organism;

[0065] By adjusting the ratio of large nanoparticles to small nanoparticles, the release rate and time of the drug can be more precisely controlled, allowing the drug to be released in a more stable manner over a longer period of time, thereby improving the therapeutic effect and reducing side effects;

[0066] Since the drug release is more stable and lasts longer, the therapeutic effect will be significantly improved. By precisely controlling the drug release rate and time, the peak concentration and fluctuation of the drug can be reduced, thereby reducing the incidence and severity of side effects. Since the drug release is more stable and lasts longer, patients can receive treatment more conveniently without frequent dosing or dosage adjustment, thereby improving compliance.

[0067] In this embodiment, take polyethylene glycol: L-lactide = 1:5 as an example;

[0068] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 48 hours is 23%; the cumulative release after 14 days is 51%.

[0069] Embodiment 3

[0070] Example 2 uses nanoparticles of different particle sizes to reduce free drug molecules, and is further improved on the basis of Example 2 to meet the needs of sustained-release for different patients.

[0071] Unwrapped graphene oxide was loaded with semaglutide in the same way as nanoparticles and then directly mixed into dodecyl-modified hydroxypropyl methylcellulose;

[0072] The particle size of graphene oxide is less than 200 nm; the mass ratio of unwrapped graphene oxide to wrapped graphene oxide is 1:9.

[0073] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages:

[0074] Encapsulated graphene oxide nanoparticles: Since these particles are encapsulated by polyethylene glycol-polylactic acid, they have a relatively large particle size and form a relatively stable skeleton structure in the hydrogel. The drug release is relatively slow, which is conducive to achieving long-term sustained and controlled release;

[0075] Since the particle size of unencapsulated graphene oxide is less than 200 nm, the graphene oxide particles directly loaded with semaglutide can release the drug faster, provide an initial drug concentration peak, and quickly reach the desired drug concentration, making the initial in vivo drug concentration controllable, and then the encapsulated nanoparticles maintain a lower but stable drug concentration.

[0076] Graphene oxide has an extremely high specific surface area. Whether it is wrapped or unwrapped, it can effectively adsorb semaglutide molecules. Unwrapped graphene oxide has a large number of oxygen-containing functional groups on its surface, which shows a stronger drug adsorption capacity, further affecting its release characteristics.

[0077] The addition of graphene oxide can enhance the mechanical strength and stability of hydrogels. Graphene oxide sheets can form physical or chemical crosslinks with polymer chains in the hydrogel matrix, thereby extending the retention time of the hydrogel in the body.

[0078] By combining the use of wrapped and unwrapped graphene oxide, a dual release mode of the drug was achieved; initially, the unwrapped GO released the drug quickly, providing an immediate therapeutic effect; subsequently, the wrapped GO nanoparticles continued to release the drug at a slower rate to maintain the therapeutic effect;

[0079] The addition of graphene oxide enhances the structural stability of the hydrogel and prolongs its retention time in the body. At the same time, by precisely controlling the particle size distribution and encapsulation state of GO, a more precise controlled release effect is achieved. The dual release mode ensures the effective concentration of the drug in the body, which not only meets the initial treatment needs, but also ensures the long-term maintenance of the therapeutic effect.

[0080] The extended retention time and stable controlled-release effect allow patients to reduce the frequency of dosing, improve the convenience of treatment and patient compliance; by controlling the release rate and concentration fluctuations of the drug, the potential harm of the peak drug concentration to the body can be reduced, reducing the occurrence of side effects.

[0081] In this embodiment, take polyethylene glycol: L-lactide = 1:5 as an example;

[0082] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 24 hours is 17%, the cumulative release within 48 hours is 28%; the cumulative release after 14 days is 58%.

[0083] Embodiment 4

[0084] Example 3 The initial binding and release of the hydrogel are controlled by whether the graphene oxide is wrapped or not. In order to increase the load and improve the utilization, further improvements are made on the basis of Example 3.

[0085] Graphene oxide is also roughened, including heavy roughening, medium roughening, and light roughening;

[0086] The specific method of heavy roughening is: chemical etching with 95% sulfuric acid, the reaction time is 0.5-1h;

[0087] Medium roughening is specifically: chemical etching is performed using 75% sulfuric acid with a reaction time of 0.5-1h;

[0088] Light roughening is as follows: using 20kHz ultrasonic treatment 0.5-1;

[0089] The wrapped graphene oxide was combined with unwrapped graphene oxide using different roughening treatments;

[0090] The technical solutions in the above embodiments of the present application have at least the following technical effects or advantages:

[0091] Heavy roughening can significantly increase drug loading because the high specific surface area provides more binding sites. However, it can also easily lead to increased initial drug release because surface defects and roughness may accelerate drug dissolution and release.

[0092] Medium roughness: While increasing the drug loading, the drug release rate is relatively gently controlled. Medium roughness treatment is more suitable for drug delivery systems that require a medium release rate.

[0093] Light roughness: Increasing the surface roughness through physical vibration helps the uniform adsorption and sustained release of drugs;

[0094] The rough treatment of graphite oxide wrapped by nanoparticles affects the sustained-controlled release process of the entire hydrogel, while the unwrapped ones only affect the early release.

[0095] For example, combination 1: heavy rough unwrapped GO + light rough wrapped GO;

[0096] Application scenarios: drug delivery systems in rapid treatment;

[0097] Heavy rough unwrapped GO can be used to quickly deliver high concentrations of chemotherapy drugs in the early stage due to its high specific surface area and rapid release properties, achieving rapid therapeutic effects, while light rough wrapped GO can maintain stable drug release for a longer period of time, reduce the rapid clearance of drugs in the body, and extend the therapeutic window;

[0098] In this embodiment, take polyethylene glycol: L-lactide = 1:5 as an example;

[0099] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 24 hours is 23%, the cumulative release within 48 hours is 32%; the cumulative release after 14 days is 62%.

[0100] Combination 2: heavy rough wrapped GO + medium rough unwrapped GO;

[0101] Application scenarios: Insulin delivery in daily treatment of diabetes;

[0102] In diabetes management, it is necessary to simulate the natural insulin secretion pattern of the pancreas. Heavy-coarse coated GO provides a relatively gentle but sustained insulin release to simulate basal insulin secretion; while medium-coarse uncoated GO can quickly respond to blood sugar increases after a meal and provide pulsed insulin release to better control postprandial hyperglycemia.

[0103] In this embodiment, take polyethylene glycol: L-lactide = 1:5 as an example;

[0104] The cumulative release of the hydrogel prepared by this method in the environment of pH 7.4 within 24 hours is 14%, the cumulative release within 48 hours is 25%; the cumulative release after 14 days is 53%.

[0105] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A NPs hydrogel containing semaglutide, characterized in that: The invention comprises a main drug, polylactic acid nanoparticles, dodecyl-modified hydroxypropyl methylcellulose and PBS; wherein the polylactic acid nanoparticles are prepared by polyethylene glycol-polylactic acid-wrapped graphene.

2. The NPs hydrogel containing semaglutide according to claim 1, characterized in that: The main drug is semaglutide, and the concentration of semaglutide in the hydrogel is 2-20 mg / ml.

3. The NPs hydrogel containing semaglutide according to claim 1, characterized in that: The polylactic acid nanoparticles and the dodecyl-modified hydroxypropyl methylcellulose are calculated in weight percentage as follows: 1-2 wt % of the dodecyl-modified hydroxypropyl methylcellulose and 10 wt % of the polylactic acid nanoparticles.

4. The NPs hydrogel containing semaglutide according to claim 3, characterized in that: In the polylactic acid nanoparticles, the weight percentage of graphene oxide is 10wt%.

5. A method for preparing NPs hydrogel containing semaglutide according to any one of claims 1 to 4, characterized in that: Specifically include: S1, dispersing graphene oxide powder in DMF or PBS, and making it uniformly dispersed by ultrasonic treatment; S2. Under the protection of inert gas, polyethylene glycol, L-lactide and the catalyst are uniformly mixed; at the same time, the dispersed graphene oxide solution is slowly added to the copolymer reaction system while stirring; The mass ratio of polyethylene glycol to L-lactide is 1:(2-9); S3, heating the reaction system to 110-130°C, stirring the reaction for 16-24h, polymerizing the polyethylene glycol and L-lactide to form a polyethylene glycol-polylactic acid block copolymer, and in the process wrapping the graphene oxide inside the copolymer; dissolving the polyethylene glycol-polylactic acid block copolymer in DMSO, and dripping it into water under high-speed stirring to form a nanoparticle suspension; Purify by centrifugation and resuspend in PBS to obtain nanoparticle solution; S4, mixing the semaglutide solution with the nanoparticle solution, encapsulating the semaglutide into the nanoparticles, and using graphene oxide to adsorb the semaglutide; filtering out the nanoparticles S5. Prepare a 1-2 wt % dodecyl-modified hydroxypropyl methylcellulose solution; when in use, add nanoparticles to the dodecyl-modified hydroxypropyl methylcellulose solution and stir evenly to obtain NPs hydrogel containing semaglutide.

6. The method for preparing NPs hydrogel containing semaglutide according to claim 5, characterized in that: Nanoparticle hydrogel is administered subcutaneously for treatment, and the dosage is adjusted based on the condition of the disease.

7. The method for preparing NPs hydrogel containing semaglutide according to claim 5, characterized in that: The particle size of the nanoparticles is 30-200nm; the single-layer sheet size of the graphene oxide used is no more than 200nm; and the oxygen content is 30%.

8. The method for preparing NPs hydrogel containing semaglutide according to claim 7, characterized in that: When filtering and screening nanoparticles, particles with a particle size greater than 200nm are also screened for the second time to screen out large nanoparticles of 200-300nm and mix them with the screened nanoparticles. The nanoparticles screened for the second time are large nanoparticles, and the nanoparticles screened for the first time are small nanoparticles. The mass ratio of large nanoparticles to small nanoparticles is 1:

14.

9. The method for preparing NPs hydrogel containing semaglutide according to claim 8, characterized in that: After unwrapped graphene oxide was loaded with semaglutide in the same way as nanoparticles, it was directly mixed into dodecyl-modified hydroxypropyl methylcellulose; The particle size of graphene oxide is less than 200 nm; the mass ratio of unwrapped graphene oxide to wrapped graphene oxide is 1:

9.

10. The method for preparing NPs hydrogel containing semaglutide according to claim 9, characterized in that: Graphene oxide is also roughened, including heavy roughening, medium roughening, and light roughening; The specific method of heavy roughening is: chemical etching with 95% sulfuric acid, the reaction time is 0.5-1h; Medium roughening is specifically: chemical etching is performed using 75% sulfuric acid with a reaction time of 0.5-1h; Light roughening is as follows: using 20kHz ultrasonic treatment 0.5-1; The wrapped graphene oxide was combined with unwrapped graphene oxide using different roughening treatments.