A series of acid-sensitive degradable and temperature-sensitive polymers and drug-loaded compositions thereof

Abstract

We disclose a series of acid-sensitive degradable and temperature-sensitive polymers and drug-carrying compositions containing them. The polymers have the structure of formula (1) and are degradable and temperature-sensitive under physiological conditions, i.e., solid below the phase transition temperature and liquid above the phase transition temperature. Therefore, they are stable under low-temperature storage conditions and have good fluidity in the usage environment, maintaining good drug release properties and degradability, as well as stability during storage and needle passability during injection. We also disclose methods for preparing the polymers and pharmaceutical compositions containing the polymers. [Formula 1] TIFF2025528954000021.tif35153

Description

[Technical Field]

[0001] The present invention relates to the technical fields of biomedicine and polymeric medical materials, and more particularly to a series of polymers having acid-sensitive decomposition and positive temperature sensitivity, methods for preparing the same, and pharmaceutical compositions. [Background technology]

[0002] In the research field of sustained and controlled drug release, the characteristics of sustained-release materials are one of the key factors that determine the success of formulation design. An ideal sustained-release injectable material must possess good biocompatibility, effective control over drug release, and good injectability. In situ gels commonly used in drug delivery are classified into natural and synthetic gel materials based on their origin. These materials form gels in situ after injection through mechanisms such as reverse temperature sensitivity (a sol at low temperatures within a specific temperature range, which crosslinks to form a gel as the temperature increases), positive temperature sensitivity at high temperatures (a sol at high temperatures, which forms a gel as the temperature decreases after injection), pH sensitivity, chemical crosslinking, or solvent exchange, and function as a drug reservoir that slowly releases the drug. Drug release mechanisms include diffusion and dissolution. However, the above-mentioned conventional in situ gel materials have the following problems to a greater or lesser extent: poor biocompatibility, difficult metabolism, chemically cross-linked monomers have certain toxic effects, unstable drug release characteristics, high water content in the system increases the risk of degradation, and conventional positive temperature-sensitive materials may cause pain to patients and even local necrosis due to the injection temperature being too high.

[0003] Polyorthoesters are a type of polymeric substance containing many orthoester bonds, which can be hydrolyzed in an aqueous environment, resulting in excellent biodegradability. Due to their excellent biodegradability and surface solubility, polyorthoesters have rapidly developed in the field of sustained and controlled drug release, and are currently used in the commercial drug formulation Sustol® developed by Heron Therapeutics.

[0004] Classical polyorthoesters are available in semi-solid form, and related products are sold as prefilled injectables, but their rheological properties are still insufficient. Classical semi-solid polyorthoesters have high viscosity and low fluidity in the intended environment, resulting in poor needle passability during injection. When used alone as an in situ sustained-release matrix, injection administration is difficult. Therefore, when used as a sustained-release carrier for injection, classic semi-solid polyorthoesters must be mixed with a certain proportion of viscosity modifiers (e.g., dimethyl sulfoxide, N-methylpyrrolidone, or other organic solvents) to improve needle passability. However, the addition of these viscosity modifiers increases the risk of side effects such as irritation and toxicity. Furthermore, the rheological properties of classic semi-solid polyorthoesters are only very limitedly affected by temperature, maintaining a consistent fluidity even at low temperatures during storage. Therefore, during long-term storage, prefilled injectables may experience drug particle aggregation, drug crystallization, and precipitation, which can adversely affect the quality of the formulation.

[0005] Currently, patents related to polyorthoester-based polymers as drug carriers mainly include: (1) Composition of polyorthoester and aprotic solvent (Application No.: CN201480028192), (2) Long-acting polymer delivery system (Application No.: CN201580033564), and (3) Novel polyorthoester pharmaceutical auxiliary materials and novel formulations for sustained-release drugs (Application No.: CN201210436124). Patents (1) and (2) were filed by Heron Therapeutics, Inc. in the United States, and are patents for the application of polyorthoesters as sustained-release drug carriers. The polyorthoesters used are conventional semi-solid polyorthoesters. While semi-solid polyorthoesters have some effectiveness in controlling drug release, their rheological properties limit their use. Simply using classic semi-solid polyorthoesters results in high viscosity and poor fluidity in the application environment, making them difficult to meet injection needs. To address the problem of difficult injection of pharmaceutical compositions, the above patents provide pharmaceutical compositions containing a "viscosity modifier." However, while suitable viscosity modifiers (including dimethyl sulfoxide, N-methylpyrrolidone, dimethylacetamide, and other organic solvents) improve the fluidity of the composition, they may also increase the irritation and toxicity of the pharmaceutical composition, thereby increasing the risk of formulation application. However, conventional polyorthoesters still exhibit a certain fluidity at storage temperatures, which exposes the composition to the risk of drug crystallization and precipitation. Furthermore, the content of related U.S. patents (e.g., U.S. Pat. No. 10,398,686, U.S. Pat. No. 10,357,570, U.S. Pat. No. 10,213,510, etc.) is similar to the above patents (1) and (2).

[0006] Patent (3) relates to novel polyorthoesters and related sustained-release formulations that differ from conventional polyorthoester structures. This patent focuses on a method for synthesizing novel polymers rich in orthoester structures. In addition to conventional polyorthoester synthesis routes, it provides a novel polyorthoester structure and a synthesis route that are similarly biodegradable. It is anticipated that these polymers will be used as pharmaceutical auxiliary materials, particularly sustained-release drug carriers. However, due to their unique decomposition route, these novel polyorthoesters pose a higher safety risk than conventional polyorthoesters. During the degradation process, one of the final degradation products of the five-membered ring of the orthoester is formic acid. This degradation product is optic neurotoxic, significantly limiting the prospects for clinical application.

[0007] Compared with the above inventions, the novel polymer containing an orthoester structure provided by the present invention maintains the high safety and excellent sustained drug release properties of conventional polyorthoesters while creatively introducing positive temperature-sensitive properties, so that pharmaceutical compositions prepared with this polymer maintain good drug release properties and degradability, as well as stability during storage and needle passability during injection. In other words, this type of polymer and its drug-carrying system have advantages such as stable storage, convenient administration, smooth drug release, and controllable degradation, and are of great application and research value in the medical field. Summary of the Invention

[0008] Problems that the invention aims to solve One of the objectives of the present invention is to provide a series of polymers with acid-sensitive degradability and positive temperature sensitivity, and a method for preparing the same. This series of polymers has advantages such as acid-sensitive degradability, positive temperature sensitivity, and excellent biocompatibility. The preparation method is simple and easy to control.

[0009] Another object of the present invention is to provide an oligomeric monomer and a preparation method thereof, which can be used to synthesize the above series of polymers with acid-sensitive decomposition and positive temperature sensitivity, and has the characteristics of easy synthesis, easy availability of raw materials, low cost, etc.

[0010] Another object of the present invention is to provide a drug conjugate containing the above series of polymers having acid-sensitive degradability and positive temperature sensitivity as a sustained release matrix.

[0011] Means to solve the problem Thus, the present invention provides a temperature-sensitive polymer represented by the structure of formula (1). [ka] wherein x and y are independently integers greater than 1; R1 has the following structure: [ka] where: s is an integer from 0 to 30, t is an integer from 0 to 30, R4 is hydrogen or methyl; R2 is C 1-4 is alkyl, R3 has the following structure: [ka] where: R5 is a C 1-30 alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R6 is hydrogen or C 1-4 is alkyl, n is an integer from 1 to 20.

[0012] The polymer of the present invention is preferably obtained by polymerizing the following three monomers: Monomer A: 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane or a homolog thereof; Monomer B: diol, and Monomer C: An oligomer monomer represented by formula (2) or (3). [ka] (In the formula, R5 is a C 1-30 alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R6 is hydrogen or C 1-4 is alkyl, n is an integer from 1 to 20.

[0013] In the polymer of the present invention, more preferably Monomer A is 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane, 3,9-di(propylene)-2,4,8,10-tetraoxaspiro[5,5]undecane, Monomer B is a diol (triethylene glycol or tripropylene glycol), For monomer C, R5 is a C 1-30 alkyl, where the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, and an ester bond; R6 is hydrogen or C 1-2 is alkyl, n is an integer from 1 to 15.

[0014] In the polymer of the present invention, particularly preferred are Monomer A is 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane, For monomer C, R5 is a C 1-30 alkyl, where the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, and a carbonyl; R6 is hydrogen or C 1-2 is alkyl, n is an integer from 1 to 10.

[0015] The polymers of the present invention are most preferably the following polymers: [ka] (wherein x and y are independently integers greater than 1.)

[0016] The present invention further provides a method for preparing the polymer of the present invention, comprising carrying out a polymerization reaction of the following monomers in the presence of an organic solvent at a reaction temperature of 0 to 300°C: Monomer A: 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane or a homolog thereof; Monomer B: a diol (triethylene glycol or tripropylene glycol); and Monomer C: an oligomer monomer of formula (2) or (3). [ka] (In the formula, R5 is a C 1-30 alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R6 is hydrogen or C 1-4 is alkyl, n is an integer from 1 to 20.

[0017] The polymer of the present invention has a molecular weight of 1,000 to 50,000, preferably 1,000 to 20,000.

[0018] For the polymers of the present invention, the complex viscosity is 10,000 Pa·s or more at storage temperatures and 500 Pa·s or less at use temperatures.

[0019] The polymer of the present invention has temperature sensitivity, and the temperature at which its storage modulus and loss modulus become equal is between 4 and 40°C.

[0020] In the method for preparing the polymer of the present invention, the molar ratio of monomer B to monomer C (monomer A being 100%) is independently 0.01% to 99.99%.

[0021] The preparation method of the present invention is carried out in the presence of a reaction solvent, preferably a polar aprotic solvent, more preferably ethyl acetate, tetrahydrofuran, acetonitrile, dimethyl sulfoxide, or a mixture of these solvents, at a reaction temperature of 0 to 300°C, preferably 20 to 80°C.

[0022] The present invention further includes compositions of the polymers of the present invention.

[0023] The composition contains one or more therapeutically active agents, which are substances used to prevent, treat, or diagnose human diseases, intentionally regulate human physiological functions, and have specific indications or main functions, usage methods, and dosages, including herbal medicines, chemical drugs, and biological preparations. The therapeutically active agent is an anti-Parkinson's drug selected from levodopa, carbidopa, nitecapone, bromocriptine, pramipexole, ropinirole, selegiline, trihexyphenidyl, benzatropine, amantadine, and rotigotine.

[0024] the therapeutically active agent is an antiemetic selected from diphenhydramine, meclozine, scopolamine, trihexyphenidyl, chlorpromazine, ondansetron, granisetron, metoclopramide, and domperidone; the therapeutically active agent is a local anesthetic selected from procaine, tetracaine, lidocaine, and bupivacaine; the therapeutically active agent is a nonsteroidal anti-inflammatory drug selected from aspirin, acetaminophen, indomethacin, ibuprofen, naproxen, and meloxicam; the therapeutically active agent is a growth factor; the therapeutically active agent is a gene therapy drug; The therapeutically active agent is a protein drug or therapeutic polypeptide selected from insulin, and glucagon-like peptides.

[0025] The method for preparing the pharmaceutical composition of the present invention includes a step of mixing the polymer with a therapeutically active agent to form an inclusion, complex or composite, and the preparation temperature is 0 to 300°C, preferably 20 to 120°C.

[0026] The present invention also discloses oligomeric monomers represented by structural formula (2) or (3) that provide the polymers of the present invention. [ka] (In the formula, R5 is a C 1-30 alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R6 is hydrogen or C 1-4 is alkyl, n is an integer from 1 to 20.

[0027] In addition, in the method for preparing the oligomer monomer, the oligomer is prepared by carrying out a polymerization reaction between a monomer D having a structure of the following formula (6) or (7) and a monomer E (glycolide or lactide) under heating conditions. [ka] (In the formula, R5 is a C 1-30 alkyl, where the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino.

[0028] the molar ratio of component D to component E is 2:1 to 1:5; Preferably, the heating temperature is 80 to 260° C. The reaction time is 0.5 to 120 hours.

[0029] A specific method for preparing the polymer of the present invention comprises the following steps:

[0030] DETOSU, diol, and oligomer monomer C of formula (2) or (3) are added to the reaction in appropriate proportions. Under strict anhydrous and oxygen-free conditions, DETOSU is dissolved in a suitable reaction solvent and diol, and oligomer monomer C of formula (2) or (3) is dissolved in the reaction solvent. The solution of oligomer monomer C of formula (2) or (3) is added to the solution of DETOSU and diol to initiate the reaction. Within a few minutes, the reaction mixture reaches its boiling point. After cooling the solution to room temperature, the solvent is removed by rotary evaporation at 50-80°C.

[0031] A specific method for preparing the oligomeric monomer of the present invention includes the following steps:

[0032] The molar ratio of monoglyceride to glycolide (or lactide) is 2:1 to 1:5. Under inert gas protection, the monoglyceride and glycolide (or lactide) are added to a reaction vessel, which is then sealed and stirred at 80 to 260°C for 6 to 72 hours without adding a catalyst or solvent.

[0033] The pharmaceutical composition of the present invention specifically comprises: (i) a polymer according to claim 1; (ii) one or more therapeutically active agents dispersed or dissolved in the polymer of claim 1; The active agent is released from the composition within a predetermined time period. DETAILED DESCRIPTION OF THE INVENTION

[0034] The beneficial effects of the present invention will be further illustrated below through experimental data.

[0035] [Table 1]

[0036] Surprisingly, we discovered a novel polymer containing an orthoester structure with positive temperature sensitivity, as shown in Table 1 (the polymer from Example 2 was used in the above experiments). By adjusting the ratio of block units within the polymer molecule, we can flexibly adjust the storage and loss moduli of the polymer so that they are equal at a specific temperature within the range of 20–40°C. Furthermore, as shown in Figure 10, as the ambient temperature gradually increases above a specific temperature, the complex viscosity of the polymer also decreases sharply, significantly improving the polymer's fluidity. The temperature-sensitive rheological properties of this polymer allow it to meet various needs for long-term storage and applications, appearing as a more stable solid state in storage environments and a more fluid liquid state in use environments. Compared to conventional positive temperature-sensitive polymeric materials, its transformation temperature is lower. When used as a sustained-release drug carrier, this novel polymer's injection temperature is close to or lower than the human body temperature, simplifying the injection procedure, reducing local irritation, and alleviating patient pain. Drug conjugates prepared with this novel polymer and suitable active therapeutic agents have been shown to exhibit stable drug release behavior in in vitro release experiments, and the drug release rate can also be flexibly controlled by adjusting the proportion of the relevant structural units within the polymer.

[0037] Pharmaceutical compositions prepared with this polymer maintain good drug release and degradation properties, as well as stability during storage and needle passability during injection. In short, such polymers and their drug-carrying systems have the advantages of stable storage, convenient administration, smooth drug release, and controllable degradation, and are of great application and research value in the medical field. [Brief explanation of the drawings]

[0038] [Figure 1] In Example 1 of the present invention, two components, glyceryl monostearate (GMS) and glycolide (GA), were used in a molar ratio of 1:1, and one possible structure of the synthesized oligomer monomer is shown. [Figure 2]In Example 2 of the present invention, one possible structure of a polymer with acid-sensitive degradability and positive temperature sensitivity is shown, which was synthesized using three components: 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane (DETOSU), triethylene glycol (TEG), and glyceryl monostearate diglycolide (GMS-diGL) in a molar ratio of 90:80:20 (DETOSU:TEG:GMS-diGL). [Figure 3] 1 shows a mass spectrum of an oligomer synthesized in Example 1 of the present invention using two components, GMS and GA, in a molar ratio of 1:1. [Figure 4] 1 shows the infrared spectrum of an oligomer monomer synthesized in Example 1 of the present invention using two components, GMS and GA, in a molar ratio of 1:1. [Figure 5] This is an infrared spectrum of a polymer with acid-sensitive decomposition and positive temperature sensitivity synthesized in Example 2 of the present invention using three components: DETOSU, TEG, and GMS-diGL in a molar ratio of 90:80:20 (DETOSU:TEG:GMS-diGL). [Figure 6] In Example 2 of the present invention, a polymer (GMS-POE) with acid-sensitive degradability and positive temperature sensitivity was synthesized using three components, DETOSU, TEG, and GMS-diGL, in a molar ratio of 90:80:20 (DETOSU:TEG:GMS-diGL). The rheological properties of this polymer were measured at temperatures between 0 and 40°C. [Figure 7] In Example 2 of the present invention, the gel state of a polymer with acid-sensitive degradability and positive temperature sensitivity was synthesized using three components, DETOSU, TEG, and GMS-diGL, in a molar ratio of 90:80:20 (DETOSU:TEG:GMS-diGL), at 37°C (left) and 4°C (right). [Figure 8] 1 shows an in vitro release curve of a drug complex containing 1.25% pramipexole prepared with the above-mentioned acid-sensitive degradable and positive temperature-sensitive polymer in Example 7 of the present invention at 37° C. and pH 7.40. [Figure 9] 1 shows an in vitro release curve of a drug complex containing 3.3% granisetron prepared with the above-mentioned polymer having acid-sensitive degradability and positive temperature sensitivity at 37° C. and pH 7.40 in Example 8 of the present invention. [Figure 10] 1 is a curve showing the change in complex viscosity in the range of 0 to 40° C. for a series of novel polymers (GMS-POE) provided by the present invention. [Example]

[0039] The present invention will be further described below by way of examples. The present invention is not limited to the following examples, and various modifications and equivalent substitutions can be made to the present invention within the scope of the claims of the present invention.

[0040] Example 1 Preparation of Oligomeric Monomers The oligomeric monomer in this example was prepared from glyceryl monostearate (GMS) and glycolide (GA), with the molar ratio of the two components being 1:1.

[0041] As shown in Figure 1, glyceryl monostearate (GMS) (17.928 g, 0.05 mol) and glycolide (GA) (5.8035 g, 0.05 mol) were weighed into a pressure-resistant reaction tube, sealed under inert gas protection, and heated and stirred at 180 °C for 24 hours to obtain the product glyceryl monostearate diglycolide (GMS-diGL).

[0042] Example 2 Preparation of a polymer with acid-sensitive decomposition and positive temperature sensitivity The acid-sensitive degradable and positive temperature-sensitive polymer in this example was prepared from 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane (DETOSU), triethylene glycol (TEG), and glyceryl monostearate diglycolide (GMS-diGL) in a molar ratio of 90:80:20 (DETOSU:TEG:GMS-diGL).

[0043] As shown in Figure 2, under strict anhydrous conditions, DETOSU (1.910 g, 0.009 mol) was dissolved in 15 ml of anhydrous tetrahydrofuran (THF) and TEG (1.2014 g, 0.008 mol) in a 50 ml flask, and GMS-diGL (0.9493 g, 0.002 mol) was dissolved in 5 ml of anhydrous THF. The GMS-diGL solution was added to the DETOSU and TEG solution to initiate the polymerization reaction. Within a few minutes, the solution reached its boiling point. After cooling to room temperature, the solution was concentrated by rotary evaporation at 50 °C and then rotary evaporated at 80 °C.

[0044] Example 3 Preparation of a polymer with acid-sensitive decomposition and positive temperature sensitivity The acid-sensitive degradable and positive temperature-sensitive polymer in this example was prepared from 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane (DETOSU), triethylene glycol (TEG), and glyceryl monolaurate diglycolide (GML-diGL) in a molar ratio of 95:80:20 (DETOSU:TEG:GML-diGL).

[0045] Under strict anhydrous conditions, DETOSU (2.0164 g, 0.0095 mol) was dissolved in 15 mL of anhydrous tetrahydrofuran (THF) and TEG (1.2014 g, 0.008 mol) in a 50 mL flask, and GML-diGL (0.7807 g, 0.002 mol) was dissolved in 5 mL of anhydrous THF. The GML-diGL solution was added to the DETOSU and TEG solution to initiate the polymerization reaction. Within a few minutes, the solution reached its boiling point. After cooling to room temperature, the solution was concentrated by rotary evaporation at 50 °C and then rotary evaporated at 80 °C.

[0046] Example 4 Preparation of a polymer with acid-sensitive decomposition and positive temperature sensitivity The acid-sensitive degradable and positive temperature-sensitive polymer in this example was prepared from 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane (DETOSU), triethylene glycol (TEG), and glyceryl monooleate diglycolide (GMO-diGL) in a molar ratio of 100:85:15 (DETOSU:TEG:GMO-diGL).

[0047] Under strict anhydrous conditions, DETOSU (2.1225 g, 0.0100 mol) was dissolved in 50 ml of anhydrous ethyl acetate and TEG (1.2750 g, 0.0085 mol) in a 15 ml flask, and GMO-diGL (0.7088 g, 0.0015 mol) was dissolved in 5 ml of anhydrous ethyl acetate. The GMO-diGL solution was added to the DETOSU and TEG solution to initiate the polymerization reaction. Within a few minutes, the solution reached its boiling point. After cooling to room temperature, the solution was concentrated by rotary evaporation at 50 °C and then rotary evaporated at 80 °C.

[0048] Example 5 Preparation of Semi-Solid Drug Complex A semi-solid pharmaceutical composition containing pramipexole (PPX) as the active agent was prepared by the following method.

[0049] 1.25 wt % of pramipexole and 98.75 wt % of the polymer were stirred for 3 hours while heating to 40° C. under inert gas protection, and then cooled to room temperature to obtain a homogeneous semisolid.

[0050] Example 6 Preparation of Semi-Solid Drug Complex A semi-solid pharmaceutical composition with granisetron (GRA) as the active agent was prepared by the following method.

[0051] 3.0 wt % of granisetron and 97.0 wt % of the polymer were stirred for 3 hours while heating to 40° C. under inert gas protection, and then cooled to room temperature to obtain a homogeneous semisolid.

[0052] Example 7 In vitro release characteristics of pharmaceutical compositions The pharmaceutical composition of Example 5 was weighed into a dialysis bag and placed in a screw-cap test tube containing 15 ml of 0.2 N PBS (pH 7.4) at 37°C. The test tube was sealed and kept at a constant temperature of 37°C. At different time points, the test tube was inverted several times, and 5 ml of the release solution was taken out and replenished with an equal volume of the release medium at 37°C. The content of pramipexole in the release solution was measured by HPLC, the release degree was calculated, and a release curve was plotted (Figure 8).

[0053] Example 8 In vitro release characteristics of pharmaceutical compositions The pharmaceutical composition of Example 6 was weighed into a dialysis bag and placed in a screw-cap test tube containing 15 ml of 0.2 N PBS (pH 7.4) at 37°C. The test tube was sealed and kept at a constant temperature of 37°C. At different time points, the test tube was inverted several times, and 5 ml of the release solution was removed and replenished with an equal volume of 37°C release medium. The content of granisetron in the release solution was measured by HPLC, the release rate was calculated, and a release curve was plotted (Figure 9).

Claims

1. A temperature-sensitive polymer represented by the structure of formula (1): 【Chemical 1】 wherein x and y are independently integers greater than 1; R １ has the following structure: 【Chemistry 2】 where: s is an integer from 0 to 30; t is an integer from 0 to 30, R ４ is hydrogen or methyl, R ２ is C １－４ is alkyl, R ３ has the following structure: 【Chemistry 3】 where: R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R ６ is hydrogen or C １－４ is alkyl, n is an integer from 1 to 20.

2. The polymer according to claim 1, characterized in that it is obtained by polymerizing the following three types of monomers: Monomer A: 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane or a homolog thereof, Monomer B: a diol, and Monomer C: An oligomer monomer represented by formula (2) or (3). 【Chemistry 4】 (In the formula, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R ６ is hydrogen or C １－４ is alkyl, n is an integer from 1 to 20.

3. Monomer A is 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane or 3,9-di(propylene)-2,4,8,10-tetraoxaspiro[5,5]undecane; The monomer B is a diol having a structure represented by the following formula (4) or (5): 【Chemistry 5】 (In the formula, s is an integer from 0 to 30; t is an integer from 0 to 30, R ４ is hydrogen or methyl), In the monomer C, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, and an ester bond; R ６ is hydrogen or C １－２ is alkyl, n is an integer from 1 to 15 The polymer according to claim 2 .

4. Monomer A is 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane, In the monomer C, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, and a carbonyl; R ６ is hydrogen or C １－２ is alkyl, n is an integer from 1 to 10 The polymer according to claim 3 .

5. 10. The polymer of claim 1, 【Chemistry 6】 wherein x and y are independently integers greater than 1. The polymer of claim 1 .

6. 2. A method for preparing the polymer according to claim 1, characterized in that the polymerization reaction of the following monomers is carried out in the presence of an organic solvent at a reaction temperature of 0 to 300°C: Monomer A is 3,9-di(ethylene)-2,4,8,10-tetraoxaspiro[5,5]undecane or a homolog thereof; Monomer B is a diol having a structure of the following formula (4) or (5): Monomer C is an oligomer monomer represented by the following formula (2) or (3). 【Chemistry 7】 (In the formula, s is an integer from 0 to 30; t is an integer from 0 to 30, R ４ is hydrogen or methyl.) 【Chemistry 8】 (In the formula, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R ６ is hydrogen or C １－４ is alkyl, n is an integer from 1 to 20.

7. A composition comprising the polymer according to any one of claims 1 to 5.

8. The composition further comprises one or more therapeutically active agents and pharmaceutically acceptable auxiliary materials, the therapeutically active agents being substances used to prevent, treat, or diagnose human diseases, intentionally regulating human physiological functions, and having prescribed indications or main functions, methods of use, and dosages, including herbal medicines, chemical drugs, and biological preparations; the therapeutically active agent is an anti-Parkinson's drug selected from levodopa, carbidopa, nitecapone, bromocriptine, pramipexole, ropinirole, selegiline, trihexyphenidyl, benzatropine, amantadine, and rotigotine; the therapeutically active agent is an antiemetic selected from diphenhydramine, meclozine, scopolamine, trihexyphenidyl, chlorpromazine, ondansetron, granisetron, metoclopramide, and domperidone; the therapeutically active agent is a local anesthetic selected from procaine, tetracaine, lidocaine, and bupivacaine; the therapeutically active agent is a nonsteroidal anti-inflammatory drug selected from aspirin, acetaminophen, indomethacin, ibuprofen, naproxen, and meloxicam; the therapeutically active agent is a growth factor; the therapeutically active agent is a gene therapy agent; 8. The composition of claim 7, wherein the therapeutically active agent is a protein-based drug or therapeutic polypeptide selected from insulin, glucagon-like peptides.

9. An oligomer monomer represented by structural formula (2) or (3): 【Chemistry 9】 (In the formula, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester linkage, an amide linkage, an ether linkage, and an amino; R ６ is hydrogen or C １－４ is alkyl, n is an integer from 1 to 20.

10. 10. A method for preparing an oligomer monomer according to claim 9, wherein the oligomer is prepared by carrying out a polymerization reaction between a monomer D having a structure represented by the following formula (6) or (7) and a monomer E (glycolide or lactide) under heating conditions: The preparation method, characterized in that the molar ratio of component D and component E is 2:1 to 1:

5. 【Chemistry 10】 (In the formula, R ５ is a C with or without functional groups １－３０ alkyl, wherein the functional groups are independently selected from a carbon-carbon double bond, a carbon-carbon triple bond, a carbonyl, an aldehyde, a carboxy, an ester bond, an amide bond, an ether bond, and an amino.

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