Temperature-sensitive biological glue as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of flexible intelligent driving materials, and particularly relates to temperature-sensitive biological glue as well as a preparation method and application thereof. The temperature-sensitive biological glue comprises polycaprolactone glycol with the number-average molecular weight of 530 and polycaprolactone glycol with the number-average molecular weight of 2000, has a rapid reversible phase change effect, can be used for sealing a soft micro-robot, can take a good sealing effect and an efficient release effect into account, realizes various scenes such as in-vivo targeted drug delivery and intestinal flora sampling, and has a good application prospect in the fields of in-vivo targeted drug delivery, intestinal flora sampling and the like. Moreover, it can be guaranteed that the contained medicine cannot leak in the delivery process, the sufficient medicine delivery amount is guaranteed, and it is avoided that collected objects leak after sampling, and the collected objects are polluted by other substances in the intestinal tract environment.

Description

Technical Field

[0001] The invention belongs to the technical field of flexible intelligent driving materials, and specifically relates to a temperature-sensitive biological glue and a preparation method and application thereof. Background Art

[0002] The intestinal flora is the most important microbial community in the human body. It affects the immune, nervous, digestive and respiratory systems by affecting digestion, absorption and functional protein synthesis. The types, numbers and proportions of flora in different areas of the intestine vary greatly and there are significant individual differences. Imbalance in the intestinal microecology is associated with 90% of human diseases, such as colorectal cancer, myocardial infarction and sepsis. Therefore, precise sampling of intestinal flora is of great significance for studying the principles of flora ecological regulation, exploring the underlying mechanisms of major diseases and carrying out targeted intervention and diagnosis and treatment of flora.

[0003] Compared with capsule microrobots made of hard materials, soft microrobots based on bionics have the advantages of relatively large sample collection volume and are not easy to cause physical damage to living tissues. Soft microrobots have initially possessed the ability of efficient driving, high environmental adaptability and flexible operation in in vivo applications, and are expected to be used in high-performance directional sampling and protective transportation operations of the whole intestinal flora of living beings. For example, there is a pH-responsive hydrogel soft microrobot for targeted drug transportation. The cage-shaped robot is composed of a polymethacrylate-2-hydroxyethyl ester (PHEMA) hydrogel layer and a polyethylene glycol diacrylate (PEGDA) / Fe3O4 magnetic response layer, and is manufactured by a mask method. The hydrogel layer realizes the robot's grasping and releasing actions. When the pH value is around 8.0, the robot folds to grasp the object, and when the pH value is around 2.5 (near cancer cells), the robot unfolds to release the object; the magnetic response layer realizes the movement of the robot, controls the direction of the robot through the magnetic torque generated by the uniform magnetic field, and pulls the robot forward through the magnetic force generated by the gradient magnetic field, and finally achieves a moving speed of about 600μm / s.

[0004] However, soft robots represented by the research and development results of Li's team have a common problem: the lack of a complete infiltration and sealing mechanism makes it impossible to achieve waterproof isolation of the inner cabin of the micro-robot.

[0005] In targeted drug delivery applications, the flora and secretions in the internal environment upstream of the lesion may contaminate or neutralize the encapsulated drugs, making it impossible to achieve the ideal targeted treatment effect; at the same time, during drug transportation, larger gaps may cause drugs to leak from the robot's inner cabin, making the amount of drugs reaching the lesion less than the required amount and unable to meet the treatment requirements; some teams also seal the microrobot in advance and then send it into the body, which can ensure that the microrobot carries a sufficient amount of drugs to the lesion, but the sealing effect is not completely reversible. After reaching the lesion, the robot cannot completely release the encapsulated drugs, which also results in the amount of drugs reaching the lesion being less than the required amount.

[0006] In the application of live sampling, the existing sampling soft robots lack a reversible sealing mechanism. On the one hand, it is impossible to ensure that the robot's inner cabin is not contaminated by upstream environmental substances before reaching the sampling point, and that the robot's inner cabin is not contaminated by downstream environmental substances during the process of taking out the samples after sampling, which greatly affects the subsequent analysis accuracy of the collected samples; on the other hand, the lack of a sealing mechanism may cause the sample to leak after the robot takes the sample. If the sample collected contains pathogenic microorganisms (such as cancer cells, etc.), it may lead to the spread of pathogenic microorganisms (such as the spread of cancer cells).

[0007] In general, existing soft microrobots cannot achieve both good sealing effects and efficient release, and it is difficult to complete targeted drug delivery in a multi-phase mixed environment; existing sampling soft microrobots lack a reversible sealing mechanism, and there is a risk of cross-contamination and pathogen transfer during the sampling process, and cannot meet the requirements of pollution-free and leakage-free intestinal sampling samples. Summary of the invention

[0008] In view of this, the object of the present invention is to provide a thermosensitive biological glue, which has a rapid reversible phase change effect and can be used to seal a soft microrobot, and can take into account both good sealing effect and efficient release effect.

[0009] In order to achieve the above object, the present invention provides the following technical solutions:

[0010] The invention provides a temperature-sensitive biological glue, comprising: polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000.

[0011] Preferably, the volume ratio of the polycaprolactone diol having a number average molecular weight of 530 to the polycaprolactone diol having a number average molecular weight of 2000 is 5 to 7:1.

[0012] Preferably, the melting point of the thermosensitive biological glue is 36.5-43.8°C.

[0013] The present invention also provides a method for preparing the temperature-sensitive biological glue described in the above technical solution, comprising the following steps:

[0014] The thermosensitive biological glue is obtained by mixing polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000, performing ultrasonic treatment, and then oscillating.

[0015] Preferably, the temperature of the ultrasonic treatment is 70-100° C.; the power of the ultrasonic treatment is 240 W; and the time of the ultrasonic treatment is 5-10 min.

[0016] Preferably, the oscillation speed is 1500-2500 rpm; and the oscillation time is 5-10 min.

[0017] The present invention also provides the use of the temperature-sensitive biological glue described in the above technical solution or the temperature-sensitive biological glue prepared by the preparation method described in the above technical solution in the preparation of a targeted drug delivery component.

[0018] The present invention also provides the use of the temperature-sensitive biological glue described in the above technical solution or the temperature-sensitive biological glue prepared by the preparation method described in the above technical solution in preparing an intestinal flora sampling component.

[0019] Preferably, the targeted drug delivery component and the intestinal flora sampling component are soft microrobots coated with the temperature-sensitive biological glue.

[0020] Preferably, when the soft microrobot coated with the thermosensitive biological glue is a targeted drug delivery component, the edges and gaps of the soft microrobot that has been loaded with drugs and deformed into a capsule or tetrahedron are sealed in advance with the thermosensitive biological glue outside the human body;

[0021] When the soft microrobot coated with the temperature-sensitive biological glue is an intestinal flora sampling component, the temperature-sensitive biological glue is coated on the soft microrobot that is not deformed and is flat.

[0022] The present invention provides a thermosensitive biological glue, including: polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000. Polycaprolactone diol (PCL) has good shape memory temperature control properties, and can achieve reversible adhesion like paraffin melting and solidification. The present invention prepares polycaprolactone diols of different molecular weights into thermosensitive biological glue, and applies it to the sealing of soft microrobots. It can achieve multiple scenarios such as in vivo targeted drug delivery and intestinal flora sampling by controlling the rapid reversible phase change (melting and solidification) of the thermosensitive biological glue, and can ensure that the contained drug will not leak during the delivery process, ensure sufficient drug delivery, avoid leakage of collected materials after sampling (such as collecting cancer cells, cancer cell leakage may cause cancer cell metastasis), and other substances in the intestinal environment cause contamination to the collected materials (such as contamination of other substances when detecting diseases may affect the judgment of symptoms). BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of the expansion and closure of the soft microrobot;

[0024] Figure 2 It is the phase transition temperature range diagram of polycaprolactone diol with different molecular weights and different ratios;

[0025] Figure 3It is a schematic diagram of the solid-liquid state switching of the temperature-sensitive biological glue coating of the present invention within a temperature difference of 37 to 42°C;

[0026] Figure 4 This is a temperature-time function graph of the soft microrobot of Application Example 1 under an alternating magnetic field with a power of 3.0 to 4.5 kW in air. DETAILED DESCRIPTION

[0027] The invention provides a temperature-sensitive biological glue, comprising: polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000.

[0028] Unless otherwise specified, the present invention has no special requirements on the sources of the raw materials used, and commercially available products known to those skilled in the art may be used.

[0029] As an embodiment, the volume ratio of the polycaprolactone diol with a number average molecular weight of 530 to the polycaprolactone diol with a number average molecular weight of 2000 is 5 to 7:1, and in a specific embodiment, it is 7:1.

[0030] As an embodiment, the melting point of the thermosensitive biological glue is 36.5-43.8°C, as another embodiment, it is 39.1-43.8°C, 37.9-43.4°C, 36.5-43.3°C or 37-42°C, and in a specific embodiment, it is 36.5-43.3°C or 37-42°C.

[0031] Polycaprolactone diol (PCL), also known as poly-ε-caprolactone, has the appearance of a white solid powder, is non-toxic, insoluble in water, and easily soluble in a variety of polar organic solvents. PCL has good shape memory temperature control properties, and can achieve reversible adhesion like the melting and solidification of paraffin. The present invention formulates polycaprolactone diols of different molecular weights into thermosensitive biological glue, which is applied to the sealing of soft microrobots. It can achieve in vivo targeted drug delivery, intestinal flora sampling and other scenarios by controlling the melting and solidification of thermosensitive biological glue, and can ensure that the contained drugs will not leak during the delivery process, ensuring sufficient drug delivery, avoiding leakage of collected materials after sampling (such as collecting cancer cells, cancer cell leakage may cause cancer cell metastasis), and other substances in the intestinal environment. Contamination of the collected materials (such as contamination by other substances when detecting diseases may affect the judgment of symptoms).

[0032] The present invention also provides a method for preparing the temperature-sensitive biological glue described in the above technical solution, comprising the following steps:

[0033] The thermosensitive biological glue is obtained by mixing polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000, performing ultrasonic treatment, and then oscillating.

[0034] As an embodiment, the temperature of the ultrasonic treatment is 70-100°C, and in a specific embodiment, it is 80°C; the power of the ultrasonic treatment is 240W; and the time of the ultrasonic treatment is 5-10 minutes, and in a specific embodiment, it is 5 minutes.

[0035] As an implementation manner, the rotation speed of the oscillation is 1500-2500 rpm, and in a specific embodiment, it is 2000 rpm; the oscillation time is 5-10 minutes, and in a specific embodiment, it is 5 minutes.

[0036] The present invention also provides the use of the temperature-sensitive biological glue described in the above technical solution or the temperature-sensitive biological glue prepared by the preparation method described in the above technical solution in the preparation of a targeted drug delivery component.

[0037] The present invention also provides the use of the temperature-sensitive biological glue described in the above technical solution or the temperature-sensitive biological glue prepared by the preparation method described in the above technical solution in preparing an intestinal flora sampling component.

[0038] As an embodiment, the targeted drug delivery component and the intestinal flora sampling component are soft microrobots coated with the temperature-sensitive biological glue.

[0039] As an embodiment, when the soft microrobot coated with the thermosensitive biological glue is a targeted drug delivery component, the edges and gaps of the soft microrobot that has been loaded with drugs and deformed into a capsule or tetrahedron are sealed in advance with the thermosensitive biological glue outside the human body;

[0040] When the soft microrobot coated with the temperature-sensitive biological glue is an intestinal flora sampling component, the temperature-sensitive biological glue is coated on the soft microrobot that is not deformed and is flat.

[0041] As an implementation method, the process of targeted drug delivery using a soft microrobot coated with the thermosensitive biological glue is as follows: the edges and gaps of a soft microrobot that has been loaded with drugs and deformed into a capsule or tetrahedron shape are pre-coated with the thermosensitive biological glue outside the human body for sealing; after the sealed soft microrobot is delivered to the lesion site in the human body, the lesion site is locally heated outside the human body, and the thermosensitive biological glue melts to release the drug.

[0042] As an implementation method, the process of sampling intestinal flora using a soft microrobot coated with the thermosensitive biological glue is as follows: the thermosensitive biological glue is coated on a soft microrobot that is not deformed and is in a flat state, and the soft microrobot coated with the thermosensitive biological glue is sent to an intestinal sampling position in the human body. After the sampling is completed, the intestinal sampling position is locally heated outside the human body, and the thermosensitive biological glue melts and flows to the gap of the soft microrobot to cover the entire soft microrobot, and the local heating is cancelled, and the thermosensitive biological glue solidifies to complete the sealing of the soft microrobot.

[0043] As an implementation manner, the local heating is heating by applying a radio frequency alternating magnetic field.

[0044] As an embodiment, the material of the soft microrobot includes polydimethylsiloxane, magnetic particles and a curing agent; the magnetic particles are Fe3O4; the curing agent is 184Silicone Elastomer CuringAgent; the mass ratio of polydimethylsiloxane, magnetic particles and curing agent is 15:16:1; the preparation method of the material of the soft microrobot is to mix polydimethylsiloxane, magnetic particles and curing agent for curing, the curing temperature is 75°C, and the insulation time is 8h.

[0045] High-frequency alternating magnetic fields can be applied to soft microrobots to convert electromagnetic energy into heat energy. The high-temperature effect of magnetic particles (Fe3O4) encapsulated in polydimethylsiloxane (PDMS) under high-frequency alternating fields is due to Neel relaxation and hysteresis losses. Neel relaxation is caused by the rotation of the magnetic moment inside the magnetic particles, which is self-aligned with the applied high-frequency alternating field. Hysteresis losses are caused by the magnetization and demagnetization of the magnetic domains of the magnetic particles. Because the Fe3O4 magnetic particles are fixed in the PDMS polymer matrix, Neel relaxation and hysteresis losses can achieve a local high-temperature effect on the body of the soft microrobot.

[0046] As an implementation mode, the power of the radio frequency alternating magnetic field is 3-4.5 kW, 4.5 kW in a specific embodiment, and the frequency is 282-402 kHz, 305 kHz in a specific embodiment; the time for applying the radio frequency alternating magnetic field is 30-60 s, 57 s in a specific embodiment.

[0047] In targeted drug delivery applications, a soft microrobot that has been loaded with drugs and deformed into a capsule / tetrahedron shape is pre-sealed using a polycaprolactone diol coating in vitro to ensure that the drugs contained therein will not leak during the delivery process; the soft microrobot is transported to a designated location in the body through a magnetic drive system, and then locally heated by high-frequency magnetic field oscillations. As the temperature rises, the polycaprolactone diol coating melts, and the soft microrobot releases the preloaded drugs, completing the targeted delivery of the drugs and ensuring sufficient drug delivery.

[0048] In the application of intestinal flora sampling, a non-deformed planar soft microrobot is pre-coated with a polycaprolactone diol coating in vitro, and the microrobot is transported to a designated position in the intestine by a magnetic drive system. After the collection is completed (the soft microrobot has been deformed into a tetrahedral structure by responding to the external magnetic field and pH), the soft microrobot is locally heated by high-frequency magnetic field oscillation and other methods, and the polycaprolactone diol coating melts into a liquid with fluidity; after a certain period of time, the liquid flows to the gap and covers the entire soft microrobot, and then the high-frequency magnetic field is turned off, the temperature is lowered, and the polycaprolactone diol coating becomes solid again, completing the secondary sealing of the robot, avoiding leakage of collected materials after sampling (such as collecting cancer cells, leakage of cancer cells may cause cancer cell metastasis) and contamination of the collected materials by other substances in the intestinal environment (such as contamination by other substances when detecting diseases may affect the diagnosis of symptoms).

[0049] Microrobot deformation mechanism: Using magnetization programming technology, the magnetic particles mixed in the polydimethylsiloxane (PDMS) hydrogel are oriented to arrange them in a specific order and form a three-dimensional magnetization curve on the body of the soft microrobot. At this time, the magnetic particles distributed throughout the body of the soft microrobot have different local magnetization directions, thereby promoting the magnetic soft composite material to produce three-dimensional shape changes under the external magnetic field. Using magnetic field stimulation, the robot can achieve multi-modal deformations such as stretching, grasping, and closing (such as Figure 1 As shown in the figure), it can meet the needs of different scenarios during intestinal flora sampling operations.

[0050] In addition, polycaprolactone diol has good biocompatibility, good organic polymer compatibility, and good biodegradability. It can be used as a cell growth support material and is compatible with a variety of conventional plastics. It can be completely degraded in 6 to 12 months under natural conditions and will not cause harm to the human body during operation.

[0051] The technical solutions of the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention, but they should not be construed as limiting the protection scope of the present invention.

[0052] Example 1

[0053] Preparation method of thermosensitive biological glue: polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000 in a volume ratio of 7:1 are mixed and placed in an ultrasonic water bath (80°C) for ultrasonic treatment at a power of 240 W for 5 minutes, and then placed in a mixer and oscillated and mixed at 2000 rpm for 5 minutes.

[0054] Example 2

[0055] The difference from Example 1 is that the volume ratio of the polycaprolactone diol with a number average molecular weight of 530 and the polycaprolactone diol with a number average molecular weight of 2000 is 6:1.

[0056] Example 3

[0057] The difference from Example 1 is that the volume ratio of the polycaprolactone diol with a number average molecular weight of 530 and the polycaprolactone diol with a number average molecular weight of 2000 is 5:1.

[0058] Comparative Example 1

[0059] Polyacrylamide gel has self-healing properties. When two pieces of gel are in direct contact, chemical bonds can be reorganized, cross-linking can be completed, and self-healing can be achieved, thereby achieving airtight isolation of the soft microrobot from the outside world and completing chemical self-locking.

[0060] However, the self-healing solution of the gel material is less reversible than the thermosensitive biological glue provided by the present invention. Although both can achieve cross-linking, in the application of targeted drug delivery, the locked structure needs to be opened, and the self-healed gel requires a lot of force to separate again. It is difficult for microrobots in the in vivo environment to provide such a large force. Polycaprolactone diol is different. It has good fluidity in liquid state and can easily complete the dynamic process of "closing-opening".

[0061] Comparative Example 2

[0062] The difference from Example 1 is that only polycaprolactone diol having a number average molecular weight of 530 is used.

[0063] Comparative Example 3

[0064] The difference from Example 1 is that only polycaprolactone diol having a number average molecular weight of 2000 is used.

[0065] Application Example 1

[0066] The process of targeted drug delivery using a soft microrobot coated with the thermosensitive biological glue prepared in Example 1 is as follows:

[0067] Preliminarily use thermosensitive biological glue to seal the edges and gaps of a soft microrobot that has been loaded with drugs and deformed into a capsule or tetrahedron shape outside the human body, and then deliver the sealed soft microrobot to the lesion site in the human body, and then locally heat the lesion site outside the human body to melt the thermosensitive biological glue and release the drugs;

[0068] The local heating is heating by applying a radio frequency alternating magnetic field;

[0069] The material of the soft microrobot includes polydimethylsiloxane, magnetic particles and a curing agent; the magnetic particles are Fe3O4; the curing agent is 184Silicone Elastomer CuringAgent; the mass ratio of the polydimethylsiloxane, the magnetic particles and the curing agent is 15:16:1; the preparation method of the material of the soft microrobot is to mix the polydimethylsiloxane, the magnetic particles and the curing agent for curing, the curing temperature is 75°C, and the insulation time is 8h;

[0070] The power of the radio frequency alternating magnetic field is 4.5 kW and the frequency is 305 kHz; the time for applying the radio frequency alternating magnetic field is 57 s.

[0071] Application Example 2

[0072] The process of sampling intestinal flora using a soft microrobot coated with the thermosensitive biological glue prepared in Example 1 is as follows:

[0073] Thermosensitive biological glue is coated on a soft microrobot that is not deformed and is in a flat surface, and the soft microrobot coated with the thermosensitive biological glue is sent to the intestinal sampling position in the human body. After the sampling is completed, the intestinal sampling position is locally heated outside the human body, and the thermosensitive biological glue melts and flows to the gap of the soft microrobot to cover the entire soft microrobot, and the local heating is cancelled, and the thermosensitive biological glue solidifies to complete the secondary sealing of the soft microrobot;

[0074] The local heating is heating by applying a radio frequency alternating magnetic field;

[0075] The material of the soft microrobot includes polydimethylsiloxane, magnetic particles and a curing agent; the magnetic particles are Fe3O4; the curing agent is 184Silicone Elastomer CuringAgent; the mass ratio of the polydimethylsiloxane, the magnetic particles and the curing agent is 15:16:1; the preparation method of the material of the soft microrobot is to mix the polydimethylsiloxane, the magnetic particles and the curing agent for curing, the curing temperature is 75°C, and the insulation time is 8h;

[0076] The power of the radio frequency alternating magnetic field is 4.5 kW and the frequency is 305 kHz; the time for applying the radio frequency alternating magnetic field is 57 s.

[0077] Performance Testing

[0078] (1) Referring to the preparation method of the thermosensitive biological glue in Example 1, the polycaprolactone diol with a molecular weight of 530 and the polycaprolactone diol with a molecular weight of 2000 were set to 5:1, 6:1, 7:1, 8:1, 9:1, and 10:1, respectively, and the melting point range of polycaprolactone diol (PCL) with different ratios was measured. Then, repeated experiments were performed to avoid the interference of accidental errors as much as possible, and the average value of multiple experimental data was taken. The results are as follows: Figure 2 shown. Figure 2 This is a diagram of the phase transition temperature range of polycaprolactone diols with different molecular weights and different ratios.

[0079] Depend on Figure 2 It can be seen that the PCL ratio of 530:2000=7:1 is determined to be the best ratio. At this time, the melting point range of PCL is 36.5-43.3°C, and it begins to melt at 36.5°C and melts completely at 43.3°C. Under normal circumstances, the temperature range allowed by the human body is around 37-42°C. Therefore, the temperature-sensitive biological glue provided by the present invention meets the requirements of in vivo operations.

[0080] (2) Figure 3 The figure is a schematic diagram of the solid-liquid state switching of the temperature-sensitive biological glue coating of the present invention within a temperature difference of 37 to 42°C.

[0081] Depend on Figure 3 It can be seen that the thermosensitive biological glue of the present invention can maintain a solid state at 37°C, change from a solid state to a liquid state when the temperature is increased to 42°C, and return from a liquid state to a solid state when the temperature is reduced to 37°C.

[0082] (3) Figure 4 This is a temperature-time function graph of the soft microrobot of Application Example 1 under an alternating magnetic field with a power of 3.0 to 4.5 kW in air.

[0083] The present invention applies a 4.5kW, 305kHz radio frequency alternating magnetic field to the soft micro robot body, and the soft micro robot can respond to heating within 2 to 3 seconds, and can quickly heat up to about 65°C within 1 minute. After the radio frequency alternating magnetic field heating is turned off, the temperature quickly drops to room temperature within 20 seconds. Figure 4 It can be seen that the temperature change range of the soft microrobot (25-65°C) after applying the radio frequency alternating magnetic field covers the temperature range required for the PCL phase change (36.5-43.3°C), which can be used for in vivo heating to achieve rapid and reversible phase change of PCL.

[0084] The soft microrobot made of PDMS and ferroferric oxide has a thermal response under a high-frequency magnetic field. The soft microrobot heats up, the PCL coated on the soft microrobot heats up, and the PCL thermosensitive bioglue phase changes to complete subsequent applications.

[0085] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention rather than all the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A thermosensitive biological glue, characterized in that: include: Polycaprolactone diol having a number average molecular weight of 530 and polycaprolactone diol having a number average molecular weight of 2000.

2. The thermosensitive biological glue according to claim 1, characterized in that The volume ratio of the polycaprolactone diol with a number average molecular weight of 530 to the polycaprolactone diol with a number average molecular weight of 2000 is 5 to 7:

1.

3. The thermosensitive biological glue according to claim 1, characterized in that The melting point of the temperature-sensitive biological glue is 36.5-43.8°C.

4. The method for preparing the thermosensitive biological glue according to any one of claims 1 to 3, characterized in that: The following steps are involved: The thermosensitive biological glue is obtained by mixing polycaprolactone diol with a number average molecular weight of 530 and polycaprolactone diol with a number average molecular weight of 2000, performing ultrasonic treatment, and then oscillating.

5. The preparation method according to claim 4, characterized in that: The temperature of the ultrasonic treatment is 70-100° C.; the power of the ultrasonic treatment is 240 W; and the time of the ultrasonic treatment is 5-10 min.

6. The preparation method according to claim 4 or 5, characterized in that: The oscillation speed is 1500-2500 rpm; the oscillation time is 5-10 min.

7. Use of the thermosensitive biological glue according to any one of claims 1 to 3 or the thermosensitive biological glue prepared by the preparation method according to any one of claims 4 to 6 in preparing a targeted drug delivery component.

8. Use of the thermosensitive biological glue according to any one of claims 1 to 3 or the thermosensitive biological glue prepared by the preparation method according to any one of claims 4 to 6 in preparing an intestinal flora sampling component.

9. The use according to claim 7 or 8, characterized in that: The targeted drug delivery component and the intestinal flora sampling component are soft microrobots coated with the temperature-sensitive biological glue.

10. The use according to claim 9, characterized in that: When the soft microrobot coated with the thermosensitive biological glue is a targeted drug delivery component, the edges and gaps of the soft microrobot that has been loaded with drugs and deformed into a capsule or tetrahedron are sealed in advance with the thermosensitive biological glue outside the human body; When the soft microrobot coated with the temperature-sensitive biological glue is an intestinal flora sampling component, the temperature-sensitive biological glue is coated on the soft microrobot that is not deformed and is flat.

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