CN108619531B

CN108619531B - Biodegradable tracer material and preparation method and application thereof

Info

Publication number: CN108619531B
Application number: CN201810498500.0A
Authority: CN
Inventors: 王贵学; 罗力; 吴伟; 尹铁英; 刘元莉; 王溢
Original assignee: Chongqing University
Current assignee: Chongqing University
Priority date: 2018-05-23
Filing date: 2018-05-23
Publication date: 2021-03-30
Anticipated expiration: 2038-05-23
Also published as: CN108619531A

Abstract

The invention belongs to the field of medical materials, and particularly relates to a biodegradable tracer material which is prepared by taking PLLA (levorotatory polylactic acid) and TPE (tetraphenylethylene) as raw materials; the mass ratio of the PLLA to the TPE is 80-120: 1-5; the molecular weight of the PLLA is 60-100 ten thousand. The biodegradable tracer material prepared from the PLLA and the TPE has a copolymerization integrated luminescence effect, the PLLA is used as a material with better biological safety, the TPE is degraded along with the degradation of the PLLA in the in-vivo degradation process, so that fluorescence quenching occurs, the quenching speed is matched with the PLLA degradation speed, and the material can be better positioned and traced. The biodegradable tracer material provided by the invention can be used as a medical instrument implant, can be well slowly released and degraded in vivo, and can be used for eliminating a series of positioning and visual tracking problems caused by long-time slow degradation.

Description

Biodegradable tracer material and preparation method and application thereof

Technical Field

The invention belongs to the field of medical materials, and particularly relates to a biodegradable tracer material as well as a preparation method and application thereof.

Background

The application principle of the biodegradable material in the medical field is that under the physiological condition of an organism, the biodegradable material is degraded from macromolecular substances into small molecular substances which do not have damage to the organism through hydrolysis and enzymolysis, or the small molecular substances are automatically degraded in the organism and finally completely absorbed and excreted through the metabolism of the organism, so that toxic and side effects are not generated on the organism. Biodegradable materials have been widely used for surgical sutures, artificial skin, bone fixation materials, and in vivo drug sustained-release agents, etc.

The most common biological materials mainly include polymeric materials such as polylactic acid (PLA), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like. The polylactic acid material has excellent comprehensive performance, good biocompatibility and biodegradability, the terminal degradation products mainly comprise water and carbon dioxide, the intermediate product lactic acid is also a normal sugar metabolite in vivo, and the polylactic acid material has biological safety. Among polylactic acid materials, poly (L-lactic acid)) has the characteristics of no toxicity and no irritation due to semi-crystallinity, and the PLLA material has good biocompatibility, biodegradability and better mechanical property, the degradation product is lactic acid which can participate in the metabolism of human bodies, so that the poly (L-lactic acid) becomes one of the materials which are most important in the current biomedical field; and it has higher mechanical strength, tensile ratio and lower shrinkage, and is used for preparing cardiovascular stents.

Organic solid luminescent materials have wide application in the fields of chemical sensors, biological probes, electroluminescence, photoelectricity and the like, and become a hot topic for research of chemists, most of traditional fluorescent compounds are rigid planar molecules with a conjugated system, and show strong fluorescence in a dilute solution, but in a solid or concentrated solution, due to interaction between fluorescent chromophores, an aggregation phenomenon occurs among molecules, and finally a fluorescence quenching (ACQ) phenomenon occurs. It would be a practical finding if a class of luminescent materials could be found that exhibit fluorescence that is not reduced but enhanced in the aggregate state.

The TPE (tetraphenylethylene) has four benzene rings in the molecule, and is connected with the ethylene center through a single bond. The four benzene rings can rotate or twist freely around the ethylene stator. The individual TPE molecules in dilute solution can undergo intense intramolecular rotation as a pathway from the excited state to the ground state through nonradiative decay. In the aggregate state, in contrast, the upper non-radiative decay channels are suppressed and the radiative decay channels are opened, as the space-confining intramolecular rotation is impeded. Therefore, the TPE can become a chemical material which can emit light for a long time under an aggregation state, the luminous effect of the TPE is not easy to quench easily, and the TPE has good biosafety compatibility and can be effectively applied to the development of biomedical materials.

The patent with application number 201110113145.9 discloses a preparation method of traceable biodegradable polymer stent, organic iodine contrast agent is dispersed in degradable polymer PLLA as 'core' material, polyanhydride containing anti-restenosis drug is used as 'shell' material, and the traceable biodegradable polymer stent is prepared by adopting the combination of coaxial electrostatic spinning technology, tracer and anti-restenosis drug and polymer processing technology. The product has fast quenching time after being implanted in vivo, and has limitation in positioning and tracing.

From the current degradable polymer stent, the positioning and tracing are restrictive, the degradation speed of the L-polylactic acid material is too slow, the degradation speed cannot meet the application requirement, and the application range of the material is limited due to autophagy reaction caused after the stent material is implanted and vascular restenosis generated after the stent is explained.

Therefore, a polymer material which can better position and trace the material and has higher bending strength and tensile strength and improves the degradation rate of the polymer in organisms is developed.

Disclosure of Invention

In view of the above, the present invention provides a biodegradable tracing material, where the PLLA and the biodegradable tracing material prepared from the TPE have a copolymerization aggregation luminescence effect, and in the in vivo degradation process, the TPE undergoes fluorescence quenching along with the degradation of the PLLA, and the quenching speed is matched with the PLLA degradation speed, so as to better position and trace the material.

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

the biodegradable tracer material is prepared by taking PLLA (L-polylactic acid) and TPE (tetraphenylethylene) as raw materials; the mass ratio of the PLLA to the TPE is 80-120: 1-5; the molecular weight of the PLLA is 60-100 ten thousand.

Further, the mass ratio of the PLLA to the TPE is 80-120: 1-3; the molecular weight of the PLLA is 60-100 ten thousand.

Preferably, the molecular weight of the PLLA is 100 ten thousand.

Preferably, the mass ratio of the PLLA to the TPE is 100: 2.

The biodegradable tracer material improves the strength and toughness of the material, shortens the degradation time of the high molecular weight PLLA, does not reduce the strength, and can improve the toughness, and the formed stent has good mechanical strength, biocompatibility and biodegradability; the proportion and the polylactic acid structure conformation can be adjusted according to actual needs so as to meet the requirement that the obtained degradable stent has corresponding mechanical strength and toughness according to different implantation positions and has a controllable degradation rate.

The molecular formula of TPE is as follows: c₂₆H₂₀Molecular weight: 332.44, the blue luminescent polymer is hydrophobic, PLLA also has hydrophobic performance, through the chemical modification of TPE material, more hydrophilic functional groups can be loaded, the PLLA biomaterial can be better improved, the in vivo and in vitro degradation is more rapid, as the medical instrument implant, the slow release and degradation in vivo can be better carried out, some verification problems caused by long-time slow degradation are eliminated, and TPE has good biocompatibility and no biological toxicity. And the TPE is a non-hydrophilic substance and can well remove the substanceAnd (3) outside.

The biodegradable tracer material prepared from PLLA and TPE has a copolymerization light-emitting effect. The PLLA is used as a material with better biological property, and can be evaluated for real-time degradation through the aggregation luminescence effect in the in-vivo degradation process, so that the material can be better positioned and traced.

The TPE generates fluorescence quenching along with the degradation of the PLLA, the quenching speed is matched with the degradation speed of the PLLA, and real-time fluorescence detection can be carried out on the degradation of the PLLA.

The invention also aims to provide a preparation method of the biodegradable tracer material, which comprises the following steps:

1) adding PLLA and TPE into a solvent according to the mass, and fully dissolving;

2) mixing the mixed solution of the two substances obtained in the step 1), and fully stirring and dissolving to obtain a uniform mixture.

Further, the solvent in step 1) comprises one or more of chloroform (CHCl3), dimethyl sulfoxide (DMSO), dichloromethane, DMF (dimethylformamide). The solvent is an organic solvent with certain volatility and can be used for preparation.

Preferably, the solvent in step 1) is chloroform. Chloroform as a good organic solvent can fully dissolve PLLA and TPE thereof, and in the dissolving process, the volatilization of the solvent and the toxicity of the chloroform need to be carried out in a good ventilation environment.

Dimethyl sulfoxide (DMSO) is a sulfur-containing organic compound, is colorless and odorless transparent liquid at normal temperature, and is a hygroscopic combustible liquid. Has the characteristics of high polarity, high boiling point, good thermal stability, non-proton and water miscibility, can be dissolved in most organic matters such as ethanol, propanol, benzene, trichloromethane and the like, and is known as an universal solvent.

The preparation method is characterized in that the PLLA and the TPE are mixed according to a formula ratio and then added with trichloromethane respectively, the PLLA material is processed and prepared by the method mainly adopting a blending modification mode, and the blending modification has a very obvious cost advantage. Mix PLLA and TPE after, do not influence the performance of material itself, the addition of TPE simultaneously can make the PLLA pliability of high molecular weight obtain improving, finally makes the mechanical properties of material more stable, to later stage preparation vascular support, plays more stable effect to the holding power of blood vessel.

In the specific preparation method, 1) the PLLA and the TPE are fully mixed with the trichloromethane according to the mass, the mixing time is required to be more than or equal to 3 days, the PLLA and the TPE are completely dissolved respectively, and a dark environment is kept as much as possible in the TPE dissolving process. The dissolving temperature is kept at a stable room temperature; 2) mixing the mixed solution of the two substances obtained in the step 1), then, continuously stirring and dissolving the mixed solution sufficiently, in the dissolving process, still keeping a light-tight environment and maintaining the temperature at room temperature, in the mixing process of the two substances PLLA and TPE, ensuring that the generation of bubbles is reduced, and after the two substances PLLA and TPE are sufficiently mixed, effectively enabling the substances to form a uniform mixture, enabling a PLLA molecular chain to wrap TPE molecules well, and forming a molecular group capable of gathering and emitting light.

Further, the mass-volume ratio of the PLLA to the trichloromethane in the step 1) is 2.0 mg-3.0 mg: 80mL to 120 mL.

Further, the mass volume ratio of the TPE to the trichloromethane is 0.5-1.5 mg: 1mL to 3 mL.

Further, the temperature for dissolving in the step 1) and mixing in the step 2) is 20 ℃ to 30 ℃.

Preferably, the temperature for dissolving in step 1) and mixing in step 2) is from 25 ℃ to 28 ℃.

Under the condition of constant room temperature, the full mixing of two substances PLLA and TPE in chloroform can be better controlled, and meanwhile, bubbles generated by the materials are avoided in the mixing process, so that the later-stage membrane preparation process is optimized.

The invention also aims to provide application of the biodegradable tracer material in biomedical materials. The biological medicine material comprises a blood vessel bracket, a biodegradable membrane, an orthopedic internal fixation material, an operation suture and a polylactic acid membrane mesh material.

The positioning and tracing of the biological body such as an operation line prepared by the existing biological material after the biological material is implanted in the body are limited, the embedding of fluorescent molecules has a visualization effect, but the photobleaching and quenching time are relatively fast, so the biological material has limitations. The biodegradable tracer material prepared from PLLA and TPE can be used for tracing in vivo for a long time after being blended by using a copolymerized luminophor material. The TPE and the PLLA have biocompatibility, and can well perform in-vivo positioning on a stent or a human body implant prepared at a later stage.

After the vascular stent is prepared and implanted into a human blood vessel, the vascular stent can be positioned through Magnetic Resonance Imaging (MRI) and Computed Tomography (CT), TPE can form a fluorescence unquenching phenomenon for a long time after being blended with PLLA through the confocal luminescence advantage, the TPE can be effectively gathered in a material, and after the PLLA stent is implanted into the blood vessel, the TPE is degraded and separated along with the degradation of the material, the fluorescence intensity is continuously reduced, the real-time monitoring on the degradation of the material can be finally realized, and TPE molecules have biosafety and no toxic or side effect on a human body. After the PLLA-TPE materials are mixed, the self performance of the degradable stent can be better improved, meanwhile, the degradation condition of the polymer stent in the later period is observed in a non-invasive mode, and the analysis of the positioning of the stent on the degradation condition is better carried out.

The invention also aims to provide a method for preparing the biodegradable diaphragm by using the biodegradable tracer material prepared by the preparation method, which comprises the steps of introducing the prepared uniform mixture into a die for preparing the diaphragm to form a layer of uniform liquid level, volatilizing the solvent at the constant temperature of 37 ℃, and drying to form a film, thus obtaining the PLLA-TPE diaphragm.

The method for preparing the biodegradable film comprises the following steps: the homogeneous mixture obtained was slowly introduced into a mold made of polytetrafluoroethylene so as to be smoothly spread in the grooves of the film (groove height 2mm, area 10X 10 mm)²) To form a layer of uniform liquid level. It is placed in a 37 deg.C incubator (with vent) and kept in a ring with drynessUnder the circumstance, the trichloromethane is gradually volatilized until the liquid in the groove is completely volatilized to form a film after more than or equal to 4 days. The constant temperature and the drying environment are used for preventing the film forming quality and time from being influenced by factors such as air flow or humidity in the volatilization process, and the vent hole is used for timely removing the chloroform after the chloroform is volatilized so as to avoid poisoning. The membrane formed in the groove can be easily separated from the membrane, and after the rim charge is cut, the uniform and complete PLLA-TPE membrane is obtained.

The invention has the beneficial effects that:

1) the invention provides a biodegradable tracer material, wherein the biodegradable tracer material prepared from PLLA and TPE has a copolymerization light-collecting effect, the PLLA is used as a material with better biological property, and in the in-vivo degradation process, the TPE generates fluorescence quenching along with the degradation of the PLLA, and the quenching speed is matched with the degradation speed of the PLLA, so that the material can be better positioned and traced.

2) The TPE in the biodegradable tracer material disclosed by the invention has hydrophobicity, the PLLA also has hydrophobic property, but through chemical modification of the TPE, more hydrophilic functional groups can be loaded, the PLLA biomaterial can be better improved, the in-vivo and in-vitro degradation of the PLLA biomaterial is quicker, and the PLLA biomaterial can be better slowly released and degraded in vivo when used as an implant of a medical instrument, so that a series of verification problems caused by long-time slow degradation of the PLLA biomaterial are solved.

3) The blending of the TPE fluorescent material can better introduce the biosafety luminescent material into the PLLA material, and in the blending system, the TPE has good biocompatibility and no biological toxic action. And the TPE is a non-hydrophilic substance, so that the TPE can be well discharged from the body.

4) After the TPE and the PLLA are blended, the obtained PLLA-TPE material can be used for preparing a vascular stent, an orthopedic internal fixation material, an operation suture and a polylactic acid film mesh material (similar to an anti-adhesion membrane), can be well implanted into a body for noninvasive detection, and can be used for performing luminescence detection on the material in real time. The degradation condition of the material and the positioning condition of the material in the body are better judged and observed in real time. Has important medical detection significance.

Drawings

FIG. 1 is a schematic production line of the production method of the present invention.

FIG. 2 is a graph showing the results of the hydrophilicity and hydrophobicity of the membrane sheet.

Fig. 3 is a graph showing the results of measurement of ultimate tensile load applied to a membrane sheet.

Fig. 4 is a graph showing the results of measuring the elastic modulus of the membrane.

FIG. 5 is a graph showing the results of measurement of the change in mass of a membrane after degradation.

FIG. 6 is a graph showing the results of fluorescence intensity changes after ten weeks of degradation of the membrane.

FIG. 7 is a schematic diagram of the preparation of PLLA-TPE films.

Detailed Description

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The experimental methods of the preferred embodiments, which do not indicate specific conditions, are generally performed according to conventional conditions, and the examples are given for better illustration of the present invention, but the present invention is not limited to the examples. Therefore, those skilled in the art should make insubstantial modifications and adaptations to the embodiments of the present invention in light of the above teachings and remain within the scope of the invention.

EXAMPLE 1 preparation of biodegradable Tracer Material

The mass ratio of PLLA to TPE was 2.5 mg: 0.05mg (100: 2);

referring to fig. 1, PLLA and TPE are fully mixed with chloroform according to the above quality, and the mixing time must be ensured to be more than or equal to 3 days, so that PLLA and TPE are completely dissolved, and a dark environment is maintained as much as possible in the TPE dissolving process. The dissolving temperature is kept at a stable room temperature; the obtained mixed solution of the two substances is mixed and then is fully stirred and dissolved, the light-shielding environment is still kept and the temperature is maintained at room temperature in the dissolving process, the generation of bubbles must be reduced in the mixing process of the two substances PLLA and TPE, and after the two substances PLLA and TPE are fully mixed, the substances can be effectively made to form an even mixture, the PLLA molecular chain can well wrap TPE molecules, the molecular groups capable of gathering and emitting light are formed, and the biodegradable tracer material is obtained.

EXAMPLE 2 preparation of biodegradable Tracer Material

The mass ratio of PLLA to TPE is 2 mg: 0.025mg (80: 1);

the preparation method is shown in example 1.

EXAMPLE 3 preparation of biodegradable Tracer Material

The mass ratio of PLLA to TPE is 3mg: 0.125mg (120: 5);

the preparation method is shown in example 1.

EXAMPLE 4 preparation of biodegradable Tracer Material

Other comparative PLLA: TPE ═ 100:2, the solvent used was DMSO (dimethyl sulfoxide). The preparation method is shown in example 1.

Example 5 comparative example

The mass ratio of PLLA to TPE is 3mg: 0.02mg, otherwise prepared as in example 1.

Example 6 comparative example

The mass ratio of PLLA to TPE was 3mg to 0.2mg, otherwise prepared as in example 1.

Example 7 preparation of a PLLA-AIE Membrane

Referring to fig. 7, the thickness of the membrane is 0.10 mm-0.20 mm. The production process of the degradable membrane is as follows: slowly introducing the PLLA and TPE solution mixed at a certain ratio into a mold made of polytetrafluoroethylene to enable the solution to smoothly extend into the grooves of the mold (the height of the grooves is 2mm, and the area is 10 multiplied by 10 mm)²) To form a layer of uniform liquid level. Placing the film in a constant temperature box (with vent holes) at 37 ℃ and gradually volatilizing the trichloromethane in an environment with maintained dryness until the liquid in the groove is completely volatilized to form a film after more than or equal to 4 days. The constant temperature and the drying environment are used for preventing the film forming quality and time from being influenced by factors such as air flow or humidity in the volatilization process, and the vent hole is used for timely removing the chloroform after the chloroform is volatilized so as to avoid poisoning. The membrane formed in the groove can be easily separated from the membrane, and after the rim charge is cut, the uniform and complete PLLA-TPE membrane is obtained.

DMSO volatility is poorer than chloroform, so that the DMSO can be completely volatilized better in a longer time, and the DMSO is volatilized at a low temperature by utilizing a freeze-drying method to obtain a sample.

Example 8 measurement of Properties

PLLA-AIE membranes were prepared using the biodegradable tracer materials prepared in examples 1 to 4 and comparative examples 5 to 6 with reference to the preparation method of example 7, and the hydrophilicity and hydrophobicity, ultimate tensile load, elastic modulus, mass change after degradation, and fluorescence intensity change after ten weeks of membrane degradation were measured for the prepared PLLA-AIE membranes.

1. Testing the hydrophilicity and hydrophobicity of the membrane

The degradation speed of PLLA is influenced by molecular chain structure and terminal group number, the degradation speed of hydrophobic chlorine terminal group PLLA is obviously slower than that of hydrophilic carboxyl terminal group and hydroxyl terminal group, and the degradation speed of carboxyl terminal group PLLA is fastest, because carboxyl has hydrophilicity and can play a catalytic role in hydrolysis of ester group in molecular chain. Hydroxyl-terminated PLLA also has a faster degradation rate due to the hydrophilicity of the hydroxyl groups. For the same end group PLLA, the degradation rate of multi-arm PLLA is faster than that of linear structure PLLA because the degradation rate increases with increasing arm number, i.e., with increasing end group number. In order to improve the hydrophobicity of PLLA and the acidity of degradation products and increase the histocompatibility of PLLA, a PLLA material with fluorescence is obtained by adding TPE chemiluminescence materials so that the PLLA molecules coat the aggregated TPE molecules. The PLLA with high molecular weight plays a good role in ensuring the mechanical property of medical material preparation, so that the medical implant device obtains better hardness and supporting force. After the TPE is added into the material, the hydrophilicity and hydrophobicity of the material can be changed, so that better hydrophilicity can be obtained, a certain acceleration effect on the later-stage material implantation degradation is achieved, and the inflammation problem caused by long-term implantation of the material needs to be removed. However, the higher hydrophilicity makes the degradation accelerated too fast, which is also disadvantageous for the implantation of materials. It is important to select the PLLA to TPE blend ratio. The hydrophilicity and the hydrophobicity of the material are properly improved, so that the degradation acceleration of the material is properly improved. It is judged from the angle of the water contact angle, and the smaller the angle, the weaker the hydrophobicity and the stronger the hydrophilicity. Thus, examples 1-4 are all suitably hydrophilic, and comparative examples 5-6 (i.e., examples 5 and 6) are more hydrophilic, as shown in FIG. 2.

2. Measurement of ultimate tensile load on a membrane

The film made by blending PLLA with TPE should have good ultimate tensile strength. The ultimate tensile load is expressed in that the prepared membrane is completely subjected to plastic deformation from an original state to a tensile force, so that the deformation state cannot be recovered after the membrane is completely broken, and the maximum force in the process is the ultimate tensile load. The method has important functions on later application, modification and functional design of the material for measuring the tensile load of the material. In the later development of material application, the evaluation of the mechanical properties of the material is also very important. With the extension of time, the mechanical property of the material is gradually reduced due to the continuous degradation of the material, and after 10 weeks, the phenomenon that the brittleness of the membrane is increased and the membrane cannot be stretched occurs. Comparative examples 5-6 are more brittle after week 5, indicating that the mechanical properties have been lost, see figure 3.

3. Elastic modulus measurement of the diaphragm

The modulus of elasticity is also very important for the development of applications with materials. The elastic modulus can be defined as the stress in a unidirectional stress state divided by the strain in that direction. The elastic modulus is an important performance parameter of biomedical materials, and is a measure of the resistance of an object to elastic deformation in a macroscopic view and is a reflection of the bonding strength between atoms, ions or molecules in a microscopic view. All factors influencing the bonding strength can influence the elastic modulus of the material, such as bonding mode, crystal structure, chemical composition, microstructure, temperature and the like. The elastic modulus value fluctuates to some extent due to different material components, different heat treatment states, different cold plastic deformation and the like. Along with the degradation of the material, the elastic modulus should be gradually reduced, but the material still has certain performance retention, and has certain influence on the later support and rigidity of the material. Over time, the mixture of PLLA and TPE in an inappropriate ratio accelerates the change of the elastic modulus, and has a great influence on the later mechanical properties of the material. As can be seen from the measurements, comparative examples 5 to 6 have smaller elastic modulus than examples 1 to 4, as shown in FIG. 4.

4. Determination of the Mass Change after degradation of the Membrane

After the film pieces were prepared, rectangular film pieces each weighing 3mg were cut out, and static degradation observation was carried out, and it was found from the observation that the comparative examples 5 to 6 degraded faster than the examples 1 to 4 after ten weeks of degradation, as shown in fig. 5.

5. Change in fluorescence intensity after ten weeks of degradation of the membrane

After the membrane is degraded for ten weeks, the membrane is excited by the wavelength of 450 nm-470 nm to obtain blue excitation light. From the results of PLLA: TPE ═ 50:1, the blue fluorescence gradually quenched ten weeks after degradation. Can be explained as follows: as the PLLA molecules degrade, the encapsulated TPE groups gradually separate such that they no longer form aggregated groups, so that the luminescence decreases and quenching occurs, as shown in fig. 6.

Finally, the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered in the claims of the present invention.

Claims

1. The biodegradable tracer material is characterized by being prepared from levorotatory polylactic acid and tetraphenylethylene as raw materials; the molecular chain of the levorotatory polylactic acid is wrapped with tetraphenylethylene, and the mass ratio of the levorotatory polylactic acid to the tetraphenylethylene is 24-80: 1; the molecular weight of the L-polylactic acid is 60-100 ten thousand.

2. A method for preparing a biodegradable tracer material according to claim 1, comprising the steps of:

1) adding the levorotatory polylactic acid and the tetraphenyl ethylene into a solvent according to the mass, and fully dissolving;

3. The method according to claim 2, wherein the solvent in step 1) comprises one or more of chloroform, dimethylsulfoxide, dichloromethane, and dimethylformamide.

4. The preparation method according to claim 3, wherein the mass-to-volume ratio of the L-polylactic acid to the chloroform in the step 1) is 2.0mg to 3.0 mg: 80mL to 120 mL.

5. The preparation method according to claim 3, wherein the mass volume ratio of the tetraphenylethylene to the trichloromethane is 0.5mg to 1.5 mg: 1mL to 3 mL.

6. The method according to claim 2, wherein the temperature for the dissolution in step 1) and the mixing in step 2) is 20 ℃ to 30 ℃.

7. The method for preparing the biodegradable membrane by using the biodegradable tracer material prepared by the preparation method of any one of claims 2 to 6, wherein the prepared uniform mixture is introduced into a membrane preparation mold to form a uniform liquid level, the solvent is volatilized at a constant temperature of 37 ℃, and a thin film is formed by drying to obtain the levorotatory polylactic acid-tetraphenylethylene membrane.