CN102504215B - Block copolymers and preparation method thereof - Google Patents

Abstract

式(I)；

式(II)。The present invention provides two block copolymers, the structures of which are shown in formula (I) and formula (II) respectively. The molecular segments of the above two block copolymers contain both a hydrophobic segment-PLGA segment and a hydrophilic segment-polyethylene glycol monomethyl ether segment, thus endowing the block copolymer with amphiphilic properties . Moreover, the above-mentioned hydrophilic segment and hydrophobic segment have good biocompatibility and biodegradability, and those skilled in the art can control their physical and chemical properties by adjusting the ratio of PLGA and PEG segments, such as solubility, drug loading, etc. Quantity, circulation time in vivo, degradation rate, etc. Therefore, using the above-mentioned block copolymer as a drug carrier can improve the solubility and circulation time of the drug carrier, help to improve and improve the performance of the drug, and realize the long-term measured release of the drug;

Formula (I);

Formula (II).

Description

Block copolymer and its preparation method

technical field

The invention relates to the field of drug carrier materials, in particular to two kinds of block copolymerization and a preparation method thereof.

Background technique

Drug carriers can carry drugs, and have the functions of changing the way drugs enter the body, the distribution of drugs in the body, controlling the release rate of drugs, and delivering drugs to target organs. The use of drug carriers can reduce the degradation and loss of drugs, reduce side effects, and improve bioavailability, and its application in the field of medicine is becoming more and more extensive. Some polymer compounds have the ability to entrap drug molecules, and at the same time, they have good permeability to the membrane, so polymer drug carriers have gradually become an important research field of drug carriers.

With the continuous development of pharmacy, biodegradable polymers as drug carriers for implants have attracted more and more attention. Poly(glycolide-co-lactide) (PLGA) is a polymerized product of lactic acid and glycolic acid. non-toxic. In addition, the degradation products of poly(glycolide-co-lactide) are lactic acid and glycolic acid, and their degradation products are also by-products of human metabolism. This property makes it safe to use in medicine and biomaterials without toxic side effects. However, poly(glycolide-co-lactide) is insoluble in water and has strong hydrophobicity, so it is usually used to make hydrophobic drug carriers.

Amphiphilic polymers are a class of polymers that have both hydrophilic and lipophilic segments. In recent years, their applications in drug carriers have become more and more extensive. For example, for drugs used for intravenous injection, amphiphilic Sex drug carriers are the only option. In amphiphilic molecules, the outer shell is a hydrophilic segment, and the inner core is a hydrophobic segment. The hydrophilic segment of the outer shell enables it to be assembled in a water environment, and the hydrophilic segment also maintains the stable dispersion of the carrier in the blood environment. The hydrophobic segment of the inner core is used to entrap drug molecules, and has the functions of controlling the release rate of drugs. However, the degradability and biocompatibility of the existing amphiphilic polymers still need to be improved to improve the safety performance of their use.

Contents of the invention

The technical problem solved by the invention is to provide an amphiphilic polymer with excellent degradation performance and biocompatibility.

In view of this, the present invention provides a kind of structure such as the block copolymer shown in formula (I):

Formula (I);

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150.

Correspondingly, the present invention also provides a kind of preparation method of above-mentioned block copolymer, comprising:

Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol monomethyl ether with a double hydroxyl group at one end initiates copolymerization of glycolide and lactide in an organic solvent to obtain a structure as shown in formula (I) The block copolymer shown:

Formula (I);

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150.

Preferably, the polyethylene glycol monomethyl ether whose single end is a dihydroxyl group is prepared according to the following method:

In a stirring state, mix polyethylene glycol monomethyl ether, acetone acetal 2,2,-bis(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol in an organic solvent to obtain acetone condensation-protected bis Hydroxy polyethylene glycol monomethyl ether;

Under the condition that the pH value is 3-4, the acetone condensation-protected bishydroxypolyethylene glycol monomethyl ether is deprotected by using a cation exchange resin to obtain a polyoxyethylene glycol monomethyl ether with a single terminal of a dihydroxyl group.

Preferably, the molar ratio of polyethylene glycol monomethyl ether, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride and 4-dimethylaminopyridine is 1:(2～4):(0.5～1.5 ).

Preferably, the number average molecular weight of the polyethylene glycol monomethyl ether is 1000-40000.

The present invention also provides a block copolymer with a structure as shown in formula (II):

Formula (II);

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150.

The present invention also provides a method for preparing the above-mentioned block copolymer, comprising:

Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol with a double hydroxyl group at one end initiates the copolymerization of glycolide and lactide in an organic solvent to obtain the block copolymerization shown in structural formula (II) thing:

;

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150.

Correspondingly, the present invention also provides a kind of polyethylene glycol whose single end is a double hydroxyl group, which is prepared according to the following method:

Under stirring, polyethylene glycol, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol are mixed in an organic solvent to obtain acetone condensation-protected bishydroxypolyethylene diol;

Under the condition that the pH value is 3-4, the acetone condensation-protected dihydroxypolyethylene glycol is deprotected by using a cation exchange resin to obtain the polyethylene glycol with a single terminal of a dihydroxyl group.

Preferably, the molar ratio of polyethylene glycol, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride and 4-dimethylaminopyridine is 1:(5-7):(1.5-2).

Preferably, the polyethylene glycol has a number average molecular weight of 1000-40000.

The present invention provides two block copolymers, the structures of which are shown in formula (I) and formula (II) respectively. The block copolymerization shown in formula (I) is the Y type block copolymer of PLGA and polyethylene glycol monomethyl ether, and the block copolymerization shown in formula (II) is the dumbbell of PLGA and polyethylene glycol (PEG) type block copolymers. The molecular segments of the above two block copolymers contain both a hydrophobic segment-PLGA segment and a hydrophilic segment-polyethylene glycol monomethyl ether segment, thus endowing the block copolymer with amphiphilic properties . Moreover, the above-mentioned hydrophilic segment and hydrophobic segment have good biocompatibility and biodegradability, and those skilled in the art can control their physical and chemical properties by adjusting the ratio of PLGA and PEG segments, such as solubility, drug loading, etc. Quantity, circulation time in vivo, degradation rate, etc. Therefore, using the above-mentioned block copolymer as a drug carrier can improve the solubility and circulation time of the drug carrier, help to improve and improve the performance of the drug, and realize the long-term measured release of the drug.

Description of drawings

Fig. 1 is the proton nuclear magnetic resonance spectrogram that the single end obtained in embodiment 1 of the present invention is dihydroxypolyethylene glycol monomethyl ether b;

Fig. 2 is the proton nuclear magnetic resonance spectrogram that the single end obtained in embodiment 2 of the present invention is dihydroxypolyethylene glycol g;

Fig. 3 is the proton nuclear magnetic resonance spectrogram of the product B3 that the embodiment of the present invention 7 obtains;

Fig. 4 is the infrared spectrogram of the single-end bishydroxy polyethylene glycol monomethyl ether b obtained in Example 1 of the present invention and the product B3 obtained in Example 7 of the present invention.

Detailed ways

In order to further understand the present invention, the preferred embodiments of the present invention are described below in conjunction with examples, but it should be understood that these descriptions are only to further illustrate the features and advantages of the present invention, rather than limiting the claims of the present invention.

The embodiment of the present invention discloses a block copolymer, its structure is shown in formula (I):

Formula (I);

In formula (I), 10≤n≤1500, 10≤x≤150, 10≤y≤150. Among them, n is the degree of polymerization, x is the degree of polymerization of lactide, and y is the degree of polymerization of glycolide

The above-mentioned block copolymer is a Y-shaped block copolymer of PLGA and polyethylene glycol monomethyl ether. Among them, the PLGA chain segment is a hydrophobic chain segment, which endows the drug carrier with certain lipophilic properties, is used to entrap the drug, and regulates the circulation time of the drug in the body. The reason why PLGA is selected as the hydrophobic segment is that it is non-toxic and has good biocompatibility, blood compatibility and biodegradability, so it will not cause toxic and side effects to the body and improve the safety performance of the drug carrier.

In the above-mentioned block copolymer species, the polyethylene glycol monomethyl ether segment is used as a hydrophilic segment to provide stable dispersion in the blood environment and improve the solubility of the drug carrier in the body. The reason for choosing polyethylene glycol monomethyl ether as the hydrophilic segment is that it has good biocompatibility, low molecular weight polyethylene glycol monomethyl ether can be excreted through the kidneys, and polyethylene glycol monomethyl ether can The selected molecular weight range is wide, non-toxic, non-immunogenic and antigenic. More importantly, the terminal group of polyethylene glycol is a hydroxyl group, which is easy to modify.

It can be seen from the above that the above-mentioned Y-shaped block copolymer molecular segment provided by the present invention contains both a hydrophobic segment-PLGA segment and a hydrophilic segment-polyethylene glycol monomethyl ether segment, thus endowing the Block copolymers are amphiphilic. Moreover, the above-mentioned hydrophilic segment and hydrophobic segment have good biocompatibility. Those skilled in the art can control their physical and chemical properties by adjusting the ratio of PLGA and PEG segments, such as solubility, drug loading, and circulation in vivo. time, degradation rate, etc. Therefore, using the above-mentioned block copolymer as a drug carrier can improve the solubility and circulation time of the drug carrier, help to improve and improve the performance of the drug, and realize the long-term measured release of the drug.

Correspondingly, the present invention provides a kind of preparation method of above-mentioned block copolymerization, comprising:

Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol monomethyl ether with a double hydroxyl group at one end initiates copolymerization of glycolide and lactide in an organic solvent to obtain a structure as shown in formula (I) block copolymer shown.

The reaction formula of above-mentioned preparation method is as follows:

The reaction temperature of the above reaction is preferably 100°C to 130°C, and the reaction time is preferably controlled to be 20h to 30h. The dosage of the catalyst stannous octoate is preferably 0.8% to 1.2% of the total molar amount of polyethylene glycol monomethyl ether, glycolide and lactide with a single end having a double hydroxyl group.

The block polymerization reaction needs to control the reaction conditions to be anhydrous and oxygen-free, preferably as follows:

After dihydroxypolyethylene glycol monomethyl ether and toluene are azeotropically removed from water, glycolide and lactide are added under anhydrous and oxygen-free conditions, and the catalyst stannous octoate is added, and polyethylene glycol with double hydroxyl at one end Monomethyl ether initiates the copolymerization of glycolide and lactide in an organic solvent. After the reaction is completed, it is settled with ether and vacuum-dried to obtain a block copolymer with a structure as shown in formula (I).

Wherein, the polyethylene glycol monomethyl ether that single end is two hydroxyl groups is preferably prepared according to the following method:

In a stirring state, mix polyethylene glycol monomethyl ether, acetone acetal 2,2,-bis(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol in an organic solvent to obtain acetone condensation-protected bis Hydroxy polyethylene glycol monomethyl ether;

Under the condition that the pH value is 3-4, the acetone condensation-protected bishydroxypolyethylene glycol monomethyl ether is deprotected by using a cation exchange resin to obtain a polyoxyethylene glycol monomethyl ether with a single terminal of a dihydroxyl group.

In the above preparation method, acetone acetal 2,2'-bis(hydroxymethyl)propionic anhydride is used to modify the terminal hydroxyl group of polyethylene glycol monomethyl ether. 4-Dimethylaminopyridine is used to activate the hydroxyl group and catalyze the reaction. Methanol is used to consume unreacted acetone acetal 2,2'-di(hydroxymethyl)propionic anhydride.

In the reaction process, it is preferred to control the molar ratio of polyethylene glycol monomethyl ether, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride and 4-dimethylaminopyridine to be 1:(2～4):(0.5～ 1.5). It is preferred to select polyethylene glycol monomethyl ether with a number average molecular weight of 1000-40000. The organic solvent is preferably a mixed solution of dichloromethane and pyridine.

The polyethylene glycol monomethyl ether whose single end is double hydroxyl is specifically preferably prepared according to the following method:

Dissolve polyethylene glycol monomethyl ether in a mixed solution of dichloromethane and pyridine, add acetone acetal 2,2'-di(hydroxymethyl)propionic anhydride and 4-dimethylaminopyridine (DMAP) at room temperature , reacted overnight with stirring on a stirrer bar. Add methanol and continue stirring. After the reaction, the product is settled with ether and dried in vacuum to obtain dihydroxypolyethylene glycol monomethyl ether protected by acetone condensation;

Dissolve the dihydroxypolyethylene glycol monomethyl ether protected by acetone condensation in methanol, add cation exchange resin to the system, and react at 50°C-60°C for 3-5 hours under the condition of pH value 3-4 , filtered off the resin, and the filtrate was settled with ether to obtain a single-end bishydroxypolyethylene glycol monomethyl ether.

The present invention also provides a kind of block copolymer, its structure is as shown in formula (II):

Formula (II);

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150.

The above-mentioned block copolymerization is a dumbbell-shaped block copolymer of PLGA and polyethylene glycol (PEG), in which the PLGA segment is a hydrophobic segment, which endows the drug carrier with certain lipophilic properties, is used to entrap the drug, and regulates the drug in vivo cycle time. The reason why PLGA is selected as the hydrophobic segment is that it is non-toxic and has good biocompatibility, blood compatibility and biodegradability, so it will not cause toxic and side effects to the body and improve the safety performance of the drug carrier.

In the above block copolymers, PEG, as a hydrophilic segment, has good biocompatibility, a wide range of molecular weights to choose from, non-toxic, non-immunogenic and antigenic, and its terminal group is hydroxyl, which is easy to carry out grooming. The role of PEG is similar to that of polyethylene glycol monomethyl ether, which is used to provide its stable dispersion in the blood environment and improve the solubility of the drug carrier in the body.

The molecular segment of the dumbbell-shaped block copolymer provided by the present invention contains both a hydrophobic segment-PLGA segment and a hydrophilic segment-PEG segment, thereby endowing the block copolymer with amphiphilic properties. Moreover, the above-mentioned hydrophilic segment and hydrophobic segment have good biocompatibility. Those skilled in the art can control their physical and chemical properties by adjusting the ratio of PLGA and PEG segments, such as solubility, drug loading, and circulation in vivo. time, degradation rate, etc. Therefore, using the above-mentioned block copolymer as a drug carrier can improve the solubility and circulation time of the drug carrier, help to improve and improve the performance of the drug, and realize the long-term measured release of the drug.

Correspondingly, the present invention also provides a kind of preparation method of above-mentioned block copolymer, comprising:

Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol with a double hydroxyl group at one end initiates the copolymerization of glycolide and lactide in an organic solvent to obtain the block copolymerization shown in structural formula (II) things.

The reaction formula of above-mentioned preparation method is as follows:

The reaction temperature of the above reaction is preferably 100°C to 130°C, and the reaction time is preferably controlled to be 20h to 30h. The dosage of the catalyst, stannous octoate, is preferably 0.8% to 1.2% of the total molar amount of polyethylene glycol, glycolide and lactide with a single end having a double hydroxyl group.

The block polymerization reaction needs to control the reaction conditions to be anhydrous and oxygen-free, preferably as follows:

After dihydroxypolyethylene glycol and toluene are azeotropically removed from water, glycolide and lactide are added under anhydrous and oxygen-free conditions, and the catalyst stannous octoate is added, and polyethylene glycol with a single end of a double hydroxyl group is dissolved in an organic solvent Block copolymerization occurs with glycolide and lactide, after the reaction is completed, it is settled with ether and dried in vacuum to obtain a block copolymer with the structure shown in formula (II).

Wherein, polyethylene glycol with a single end being a dihydroxyl group is preferably prepared according to the following method:

Under stirring, polyethylene glycol, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol are mixed in an organic solvent to obtain acetone condensation-protected bishydroxypolyethylene diol;

Under the condition that the pH value is 3-4, the acetone condensation-protected dihydroxypolyethylene glycol is deprotected by using a cation exchange resin to obtain the polyethylene glycol with a single terminal of a dihydroxyl group.

During the reaction, the molar ratio of polyethylene glycol, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride and 4-dimethylaminopyridine is preferably controlled to be 1:(5-7):(1.5-2). It is preferred to select polyethylene glycol with a number average molecular weight of 1,000 to 40,000. The organic solvent is preferably a mixed solution of dichloromethane and pyridine.

Polyethylene glycol with a single end being a dihydroxyl group is preferably prepared according to the following method:

Dissolve polyethylene glycol in a mixed solution of dichloromethane and pyridine, add acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride and DMAP at room temperature, and react overnight under stirring with a stirring bar. Add methanol and continue to stir. After the reaction, the product is settled with ether and dried in vacuum to obtain dihydroxypolyethylene glycol protected by condensation of acetone;

Dissolve dihydroxypolyethylene glycol protected by acetone condensation in methanol, add cation exchange resin to the system, react at 50°C-60°C for 3-5 hours at pH 3-4, filter off resin, and the filtrate was settled with ether to obtain a single-end bishydroxypolyethylene glycol monomethyl ether.

In order to further understand the present invention, the block copolymerization provided by the present invention and its preparation method are described below in conjunction with examples, and the protection scope of the present invention is not limited by the following examples.

The descriptions of the above embodiments are only used to help understand the method and core idea of the present invention. It should be pointed out that for those skilled in the art, without departing from the principle of the present invention, some improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention. The Dowex50WX2 resins in the following examples are all provided by Sigma-Aldrich Company.

Example 1 Preparation of single-ends with different number-average molecular weights is dihydroxypolyethylene glycol monomethyl ether

1. Weigh 10g of polyethylene glycol monomethyl ether with number-average molecular weight of 1000, 5000, 10000, 20000 and 40000, numbered in sequence a', b', c', d' and e', and dissolve them respectively In a mixed solution of 60mL of dichloromethane and pyridine (v/v, 90/10);

Add 9.91g, 1.98g, 0.99g, 0.50g and 0.25g of acetone acetal 2,2'-bis(hydroxymethyl) to a', b', c', d' and e' solutions respectively at room temperature Propionic anhydride, and 1.10g, 0.22g, 0.11g, 0.055g, and 0.027g of DMAP were reacted overnight under stirring with a stirrer; methanol was added to the above solution and continued to stir for 5h. After vacuum drying for 24 hours, dihydroxypolyethylene glycol monomethyl ether protected by acetone condensation was obtained.

2. Weigh 5g of acetone condensation-protected dihydroxypolyethylene glycol monomethyl ether obtained in step 1 and dissolve in 200mL of methanol, add Dowex 50WX2 resin to the system respectively, and react at 55°C until ¹³ C NMR monitors acetone Until the protecting group peak disappears (3~5h), the resin is filtered off, and the filtrate is settled with ether to obtain a single-end bishydroxypolyethylene glycol monomethyl ether, numbered sequentially as a, b, c, d and e. See Table 1 for the number average molecular weight and the productive rate of the products obtained in step 1 and step 2.

The number average molecular weight and reaction yield of the product obtained in table 1 step 1 and step 2

experiment number Mn ₁ (g.mol ^-1 ) Reaction yield1(%) Mn ₂ (g.mol ^-1 ) Reaction yield 2(%)

a' 1158 91.5 1116 92.2 b' 5158 92.8 5116 93.5 c' 10158 93.6 10116 94.3 d' 20158 95.4 20116 96.4 e' 40158 96.2 40116 96.5

In the above table and in Table 2 below, Mn ₁ is the number average molecular weight of the first step reaction product acetone condensation protected dihydroxy polyethylene glycol monomethyl ether/acetone condensation protected dihydroxy polyethylene glycol, and the reaction yield is 1 For the productive rate of the first step reaction; Mn ₂ is the number-average molecular weight of the polyethylene glycol monomethyl ether/single end of the polyethylene glycol monomethyl ether/single end of the second step reaction product single-end being two hydroxyl groups, reaction yield 2 is the yield of the second step reaction.

Fig. 1 is the proton nuclear magnetic resonance spectrum of the single-ended dihydroxypolyethylene glycol monomethyl ether b obtained in this example. In Figure 1, around ppm=1.2 is the methyl peak on the hydroxyl side of the chain, ppm=2.3 is the hydroxyl peak, ppm=3.3 is the methoxy peak, and the rest of the characteristic peaks overlap with the PEG methylene peak. It can be seen that the product was successfully prepared.

Embodiment 2 prepares the single end of different number-average molecular weights as dihydroxypolyethylene glycol

1. Weigh 10g of polyethylene glycol with number-average molecular weight of 1000, 5000, 10000, 20000 and 40000 respectively, and dissolve them in 60mL of dichloromethane respectively with numbers f', g', h', i' and j' In a mixed solution with pyridine (v/v, 90/10);

Add 19.82g, 3.96g, 1.98g, 0.99g, 0.50g of acetone acetal 2,2'-bis(hydroxymethyl) to f', g', h', i' and j' solutions respectively at room temperature Propionic anhydride, and 2.20g, 0.44g, 0.22g, 0.11g, 0.055g of DMAP, react overnight under stirring with a stirrer; add methanol to the above solution and continue stirring for 5h. Vacuum dried for 24 hours to obtain acetonide-protected dihydroxypolyethylene glycol.

2. Weigh 5g of the acetone condensation-protected dihydroxypolyethylene glycol monomethyl ether obtained in step 1 and dissolve it in 200mL of methanol, add Dowex 50WX2 resin to the system, and react at 55°C until ¹³ C NMR monitors the acetone protection Until the base peak disappears (3~5h), the resin is filtered off, and the filtrate is settled with ether to obtain a single-ended dihydroxypolyethylene glycol, numbered sequentially as f, g, h, i, j. The number-average molecular weight and productive rate of the products obtained in each step are shown in Table 2.

Number average molecular weight and reaction yield of the product obtained in table 2 step 1 and step 2

experiment number Mn ₁ (g.mol ^-1 ) Reaction yield1(%) Mn ₂ (g.mol ^-1 ) Reaction yield 2(%) f' 1316 90.5 1232 91.3 g' 5316 91.8 5232 92.2 h' 10316 92.6 10232 93.4 i' 20316 94.4 20232 95.6 j' 40316 96.2 40232 95.8

Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of the single-end obtained in this embodiment is dihydroxypolyethylene glycol g. In the figure, around ppm=1.2 is the methyl peak on the hydroxyl side of the chain, and around ppm=2.5 is the hydroxyl peak, and the rest of the characteristic peaks overlap with the PEG methylene peak, which shows that the product was successfully prepared.

Example 3 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _10×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to remove water by azeotropy Finally, 104mg, 22.69mg, 11.47mg, 5.77mg, 2.89mg of glycolide, and 387.20mg, 84.46mg, 42.72mg, 21.48mg, 10.77mg of lactide were added under anhydrous and anaerobic conditions; then use 8mL, 2mL, 1mL, 0.5mL, 0.25mL of dry toluene were dissolved in the reactants, and 14.52mg, 3.17mg, 1.60mg, 0.81mg, 0.40mg of catalyst Sn(Oct) ₂ were added respectively, and the reaction was carried out at 120°C for 24h. After the end, it was settled with ether and dried in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _10×2 block copolymer, and the product numbers were as follows: A1, B1, C1, D1, E1, the number average molecular weight and yield of the products are shown in Table 3.

Number average molecular weight and reaction yield of table 3 product

In Table 3 and the following Tables 5, 7, 9, 11, 13, 15 and 17, Mn ₁ is the number-average molecular weight of polyethylene glycol monomethyl ether with a double hydroxyl at one end, and GA/LA/I is glycolide , the molar ratio of lactide and initiator; Mn ₂ is the number average molecular weight of Y-type polyethylene glycol monomethyl ether and poly(glycolide-co-lactide) block copolymer, by ¹ H NMR Measured; DP of GA/LA is the average polymerization of Y-type polyethylene glycol monomethyl ether and poly(glycolide-co-lactide) block copolymer GA/LA structural units derived from the number average molecular weight Spend.

Example 4 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _10×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 188.42mg, 44.37mg, 22.69mg, 11.47mg, 5.77mg of glycolide, and 701.49mg, 165.18mg, 84.46mg, 42.72mg, 21.48mg of lactide under water anaerobic conditions; then use dry toluene 17.80mL, 4.19mL, 2.14mL, 1.08mL, 0.54mL of dissolved reactant, add 26.31mg, 6.19mg, 3.17mg, 1.60mg, 0.81mg of Sn(Oct) ₂ respectively, react at 120°C for 24h, the reaction is over After settling with ether, vacuum drying at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _10×4 block copolymer, the product numbers are F1, G1, H1, I1, J1. The number average molecular weight and productive rate of the obtained product are shown in Table 4.

Number-average molecular weight and reaction yield of the product obtained in table 4

In Table 4 and the following Tables 6, 8, 10, 12, 14, 16 and 18, Mn ₁ is the number average molecular weight of polyethylene glycol with double hydroxyl at one end, GA/LA/I is glycolide, lactide The molar ratio of ester to initiator; Mn ₂ is the number average molecular weight of dumbbell-shaped polyethylene glycol and poly(glycolide-co-lactide) block copolymer, obtained by 1H NMR measurement; DP of GA/LA is the average degree of polymerization of GA/LA structural units in dumbbell-shaped polyethylene glycol and poly(glycolide-co-lactide) block copolymers derived from the number average molecular weight.

Example 5 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _20×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to azeotropically remove water , add 208.01mg, 25.38mg, 22.95mg, 11.54mg, 5.79mg glycolide, and 774.41mg, 168.93mg, 85.43mg, 42.96mg, 21.54mg lactide under anhydrous and anaerobic conditions; 20mL, 4mL, 2mL, 1mL, and 0.5mL of toluene were dissolved in 29.04mg, 6.34mg, 3.20mg, 1.61mg, and 0.81mg of Sn(Oct) ₂ , and reacted at 120°C for 24 hours. Diethyl ether was settled, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _20×2 block copolymer, and the product labels were A2 and B2 in sequence , C2, D2, E2, the number average molecular weight and productive rate of the products obtained are shown in Table 5.

Number-average molecular weight and reaction yield of the product obtained in table 5

Example 6 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _20×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 376.85mg, 88.74mg, 45.38mg, 22.95mg, 11.54mg of glycolide, and 1.40g, 330.37, 168.93mg, 85.43mg, 42.96mg of lactide under water anaerobic conditions; then use dry toluene 36mL , 8mL, 4mL, 2mL, 1mL of dissolved reactants, respectively added 52.61mg, 12.39mg, 6.34mg, 3.20mg, 1.61mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the reaction, 25 Vacuum drying at ℃ for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _20×4 block copolymer, the product numbers are F2, G2, H2, I2, J2 in sequence. The number average molecular weight and productive rate of the obtained product are shown in Table 6.

Number-average molecular weight and reaction yield of the product obtained in table 6

Example 7 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _30×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to remove water by azeotropy Finally, 312.01mg, 68.06mg, 34.42mg, 17.31mg, 8.68mg glycolide, and 1.16g, 253.39mg, 128.15mg, 64.44mg, 32.32mg lactide were added under anhydrous and anaerobic conditions; Dissolve the reactant with dry toluene 29mL, 6mL, 3mL, 1.6mL, 0.8mL, add 43.56mg, 9.50mg, 4.81mg, 2.42mg, 1.21mg of Sn(Oct) ₂ respectively, and react at 120°C for 24h. After the end, it was settled with ether, and dried in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _30×2 block copolymer, and the product numbers were as follows: A3, B3, C3, D3, E3. The number average molecular weight and productive rate of the obtained product are shown in Table 7.

Number-average molecular weight and reaction yield of the resulting product of table 7

Fig. 3 is the H NMR spectrum of Y-shaped and dumbbell-shaped polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _30×2 B3 obtained in this example. In the figure, around ppm=1.5 is the methyl peak in the lactide segment in the copolymer, ppm=3.6 is the PEG peak, ppm=4.8 is the methylene peak in the glycolide segment, ppm=5.2 The left and right are the methine peaks in the lactide chain segment, which shows that the product was successfully prepared.

Figure 4 shows that the single end obtained in Example 1 is dihydroxy polyethylene glycol monomethyl ether b and the polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) obtained in Example 7 of the present invention ) _30×2 B3 infrared spectrum. Among them, the carbonyl stretching vibration peak appears near 1750cm ^-1 , which shows that the two products were successfully prepared.

Example 8 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _30×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 565.28mg, 133.11mg, 68.06mg, 34.42mg, 17.31mg of glycolide, and 2.10g, 495.55mg, 253.39mg, 128.15mg, 64.44mg of lactide under anaerobic conditions; 53.4mL, 12.6mL, 6.4mL, 3.2mL, 1.6mL of dissolved reactant, respectively added 78.92mg, 18.58mg, 9.50mg, 4.81mg, 2.42mg of Sn(Oct) ₂ , reacted at 120°C for 24h, the reaction was completed After settling with ether, vacuum drying at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _30×4 block copolymer, the product numbers are F3, G3, H3, I3, J3. The number average molecular weight and productive rate of the obtained product are shown in Table 8.

Number-average molecular weight and reaction yield of the product obtained in table 8

Example 9 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _40×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, and put them into 5 dry reaction flasks with branched ports, add 20 mL of toluene to azeotropically remove water Finally, 416.02mg, 90.75mg, 45.90mg, 23.08mg, 11.57mg of glycolide, and 1.55g, 337.86mg, 170.87mg, 85.93mg, 43.09mg of lactide were added under anhydrous and anaerobic conditions. Toluene 39.2mL, 8.6mL, 4.2mL, 2.2mL, 1mL dissolved reactant, added 43.56mg, 9.50mg, 4.81mg, 2.42mg, 1.21mg of catalyst stannous octoate (Sn(Oct) ₂ ), at 120°C After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _40×2 block copolymer , the product numbers are A4, B4, C4, D4, E4 in turn. The number average molecular weight and yield of the obtained product are shown in Table 9.

Number-average molecular weight and reaction yield of the product obtained in table 9

Example 10 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _40×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 753.70mg, 177.48mg, 90.75mg, 45.90mg, 23.08mg glycolide, and 2.80g, 660.73mg, 337.86mg, 170.87mg, 85.93mg lactide respectively under water anaerobic conditions; 71.2mL, 16.8mL, 8.6mL, 4.4mL, 2.2mL of dissolved reactants, respectively added 105.23mg, 24.78mg, 12.67mg, 6.41mg, 3.22mg of Sn(Oct) ₂ , reacted at 120°C for 24h, the reaction was completed After settling with ether, vacuum drying at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _40×4 block copolymer, the product numbers are F4, G4, H4, I4,. The number average molecular weight and productive rate of the obtained product are shown in Table 10.

Number-average molecular weight and reaction yield of the product obtained in table 10

Example 11 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _50×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to azeotropically remove water , add 520.03mg, 113.44mg, 57.37mg, 28.85mg, 14.47mg glycolide, and 1.94g, 422.32mg, 213.58mg, 107.41mg, 53.86mg lactide respectively under anhydrous and anaerobic conditions; Dried toluene 49mL, 10.8mL, 5.4mL, 2.8mL, 1.4mL dissolved reactants, respectively added 72.60mg, 15.84mg, 8.01mg, 4.03mg, 2.02mg of Sn(Oct) ₂ , reacted at 120°C for 24h, After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _50×2 block copolymer, and the product numbers are in sequence For A5, B5, C5, D5, E5. The number average molecular weight and yield of the obtained product are shown in Table 11.

Number-average molecular weight and reaction yield of the products obtained in table 11

Example 12 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _50×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 942.13mg, 221.85mg, 113.44mg, 57.37mg, 28.85mg of glycolide, and 3.51g, 825.92mg, 422.32mg (2.93×10 ^-3 mol), 213.58mg, 107.41mg of lactide under water anaerobic conditions ; Then dissolve the reactants with dry toluene 89mL, 21mL, 10.8mL, 5.4mL, 2.8mL respectively, add 131.53mg, 30.97mg, 15.84mg, 8.01mg, 4.03mg of Sn(Oct) ₂ in decibels, at 120°C React for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _50×4 block copolymer, and the product numbers are in order It is F5, G5, H5, I5, J5. The number average molecular weight and yield of the obtained product are shown in Table 12.

Number-average molecular weight and reaction yield of the product obtained in table 12

Example 13 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _80×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to azeotropically remove water , add 832.04mg, 181.50mg, 91.79mg, 46.16mg, 23.15mg glycolide, and 3.10g, 675.72mg, 341.73mg, 171.85mg, 86.17mg lactide under anhydrous and anaerobic conditions; 78.60mL, 17.2mL, 8.6mL, 4.4mL, 2.2mL of toluene were dissolved in reactants, and 116.16mg, 25.34mg, 12.82mg, 6.44mg, 3.23mg of Sn(Oct) ₂ were added respectively, and reacted at 120°C for 24h. After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _80×2 block copolymer, and the product numbers are in sequence For A6, B6, C6, D6, E6. The number average molecular weight and yield of the obtained product are shown in Table 13.

Number-average molecular weight and reaction yield of the product obtained in table 13

Example 14 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _80×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 1.51g, 354.95mg, 181.50mg, 91.79mg, 46.16mg glycolide, and 5.61g, 1.32g, 675.72mg, 341.73mg, 171.85mg lactide under anaerobic conditions in water; then use dry toluene 142.4 mL, 33.6mL, 17.2mL, 8.6mL, 4.4mL dissolved reactants, respectively added 210.45mg, 49.56mg, 25.34mg, 12.82mg, 6.44mg of Sn(Oct) ₂ , reacted at 120°C for 24h, after the reaction Precipitation with ether, vacuum drying at 25°C for 24 hours, to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _80×4 block copolymer, the product numbers are F6, G6, H6 , I6, J6. The number average molecular weight and yield of the obtained product are shown in Table 14.

Number-average molecular weight and reaction yield of the product obtained in table 14

Example 15 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _100×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to azeotropically remove water 1.04g, 226.88mg, 114.74mg, 57.70mg, 28.93mg of glycolide, and 3.87g, 844.64mg, 427.16mg, 214.81mg (1.49×10 ^-3 mol), 107.72mg were added under anhydrous and oxygen-free conditions Lactide; then dissolve the reactant with dry toluene 98.2mL, 21.4mL, 10.8mL, 5.4mL, 2.8mL respectively, add 145.20mg, 31.68mg, 16.02mg, 8.06mg, 4.04mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the end of the reaction, and vacuum-dried at 25°C for 24h to obtain Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _100×2 Block copolymers, the product numbers are A7, B7, C7, D7, E7. The number average molecular weight and yield of the obtained product are shown in Table 15.

Number-average molecular weight and reaction yield of the product obtained in table 15

Example 16 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _100×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl groups at one end, respectively, put them into 5 dry reaction flasks with branched ports, add 20 mL of toluene to azeotropically remove water, and After azeotropic water removal for dihydroxypolyethylene glycol toluene, 1.88g, 433.69mg, 226.88mg, 114.74mg, 57.70mg glycolide, and 7.01g, 1.65g, 844.64mg ( 5.86×10 ^-3 mol, 427.16mg, 214.81mg lactide, 178mL, 42mL, 21.4mL, 10.8mL, 5.4mL of dry toluene were used to dissolve the reactant, and 263.06mg, 61.94mg, 31.68mg, 16.02mg were added respectively, 8.06 mg of Sn(Oct) ₂ was reacted at 120°C for 24 hours. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75 %) _{100 × 4} block copolymers, the product numbers are F7, G7, H7, I7, J7. The number average molecular weight and productive rate of the products obtained are shown in Table 16.

Number-average molecular weight and reaction yield of the products obtained in table 16

Example 17 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _150×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether a, b, c, d, e with a single end of a double hydroxyl group, respectively, put them into 5 dry reaction bottles with branched ports, add 20 mL of toluene to azeotropically remove water , add 1.56g, 340.32mg, 172.11mg, 86.55mg, 43.40mg glycolide, and 5.81g, 1.27mg, 640.75mg, 322.22mg, 161.58mg lactide under anhydrous and anaerobic conditions; Toluene 147.4mL, 32.2mL, 16.2mL, 8.2mL, 4mL dissolved reactant, respectively added 217.81mg, 47.51mg, 24.03mg, 12.08mg, 6.06mg of Sn(Oct) ₂ , reacted at 120°C for 24h, the reaction After the end, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 25%-lactide 75%) _150×2 block copolymer, and the product numbers were as follows: A8, B8, C8, D8, E8. The number average molecular weight and yield of the obtained product are shown in Table 17.

Number-average molecular weight and reaction yield of the products obtained in table 17

Example 18 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _150×4 block copolymer

Weigh 200 mg of polyethylene glycol f, g, h, i and j with dihydroxyl at one end, respectively, put them into 5 dry reaction flasks with branch ports, add 20 mL of toluene to remove water azeotropically, Add 2.83g, 665.54mg, 340.32mg, 172.11mg, 86.55mg glycolide, and 10.52g, 2.48g, 1.27g, 640.75mg, 322.22mg lactide under water anaerobic conditions; then use dry toluene 267mL , 62.8mL, 32.2mL, 16.2mL, 8.2mL of dissolved reactants, respectively added 394.60mg, 92.92mg, 47.51mg, 24.03mg, 12.08mg of Sn(Oct) ₂ , reacted at 120°C for 24h, and used Diethyl ether was settled, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 25%-lactide 75%) _150×4 block copolymer, and the product numbers were F8, G8, H8, I8, J8. The number average molecular weight and yield of the obtained product are shown in Table 18.

Number-average molecular weight and reaction yield of the products obtained in table 18

Example 19 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _10×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 28.64 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 0.6 mL of dry toluene, add 0.8 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _10×2 block copolymer, the product number is D9. The number average molecular weight and yield of the obtained product are shown in Table 19.

Number-average molecular weight and reaction yield of the product obtained in table 19

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D9 20116 20 23100 17 80.4

Table 19 and Tables 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65 below , 67, 69, 71, 73, 75, 77, 79 and 81, Mn ₁ is the number-average molecular weight of polyethylene glycol monomethyl ether with double hydroxyl at one end, and A/I is the ratio of lactide and initiator Feeding molar ratio; Mn ₂ is the number-average molecular weight of Y-type polyethylene glycol monomethyl ether and polylactide block copolymer, which is obtained by ¹ H NMR measurement; DP is the Y-type polyethylene glycol obtained from the number-average molecular weight The average degree of polymerization of LA structural units of alcohol monomethyl ether and polylactide block copolymer.

Example 20 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _10×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of a dihydroxy group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 56.96 mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactants in 1.2 mL of dry toluene, add 1.6 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction is completed, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol. (Lactide) _10×4 block copolymer, the product number is I9. The number average molecular weight and productive rate of the obtained product are shown in Table 20.

Number-average molecular weight and reaction yield of the product obtained in table 20

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I9 20232 40 26200 36 80.1

Table 20 and Tables 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66 below , 68, 70, 72, 74, 76, 78, 80 and 82, Mn ₁ is the number-average molecular weight of polyethylene glycol with single-end dihydroxyl groups, and A/I is the molar ratio of lactide and initiator; Mn ₂ is the number-average molecular weight of the dumbbell-shaped polyethylene glycol and polylactide block copolymer, measured by ¹ H NMR; DP is the dumbbell-shaped polyethylene glycol and polylactide block copolymer derived from the number-average molecular weight Average degree of polymerization of LA structural units.

Example 21 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _20×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 57.28 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 1.2 mL of dry toluene, add 1.61 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _20×2 block copolymer, the product number is D10. The number average molecular weight and productive rate of the obtained product are shown in Table 21.

Number-average molecular weight and reaction yield of the products obtained in table 21

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D10 20116 40 25500 36 81.5

Example 22 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _20×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 113.91 mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactant in 2.2 mL of dry toluene, add 3.20 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol. (Lactide) _20×4 block copolymer, the product number is I10. The number average molecular weight and yield of the obtained product are shown in Table 22.

Number-average molecular weight and reaction yield of the products obtained in table 22

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I10 20232 80 31900 73 81.4

Example 23 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _30×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 85.93 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 1.8 mL of dry toluene, add 2.42 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _30×2 block copolymer, the product number is D11. The number average molecular weight and yield of the product obtained are shown in Table 23.

Number-average molecular weight and reaction yield of the products obtained in table 23

experiment number Mn ₁ (g.mol ^-1 ) A/I M _n 2(g.mol ^-1 ) DP Reaction yield (%) D11 20116 60 29000 56 82.4

Example 24 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _30×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 170.87 mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactant in 3.4 mL of dry toluene, add 4.81 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol (Lactide) _30×4 block copolymer, the product number is I11. The number average molecular weight and productive rate of the obtained product are shown in Table 24.

Number-average molecular weight and reaction yield of the products obtained in table 24

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I11 20232 120 37700 114 82.2

Example 25 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _40×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 114.57 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 2.2 mL of dry toluene, add 3.22 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _40×2 block copolymer, the product number is D12. The number average molecular weight and productive rate of the obtained product are shown in Table 25.

Number-average molecular weight and reaction yield of the products obtained in table 25

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D12 20116 80 31646 69 81.7

Example 26 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _40×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, add 20 mL of toluene to azeotropically remove water, add 227.82 mg (1.58×10 ^-3 mol) of lactide under anhydrous and oxygen-free conditions, and use dry toluene 4.6mL dissolved reactants, added 6.41mg of Sn(Oct)), reacted at 120°C for 24h, settled with ether after the reaction, and vacuum dried at 25°C for 24h to obtain dumbbell-shaped polyethylene glycol-poly(lactide) ) _40×4 block copolymer, the product number is I12. The number average molecular weight and productive rate of the obtained product are shown in Table 26.

Number-average molecular weight and reaction yield of the products obtained in table 26

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I12 20232 160 45100 149 81.5

Example 27 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _50×2 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 143.21 mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactant in 2.8 mL of dry toluene, add 4.03 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction is completed, settle with ether and dry in vacuum at 25°C for 24 hours to obtain the Y-type polyethylene glycol monomethyl Ether-poly(lactide) _50×2 block copolymer, the product number is D13. The number average molecular weight and productive rate of the obtained product are shown in Table 27.

Number-average molecular weight and reaction yield of the products obtained in table 27

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D13 20116 100 35100 87 80.2

Example 28 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _50×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, and then azeotropically remove water from polyethylene glycol with a single end of dihydroxyl group Finally, add 284.78 mg of lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 5.70 mL of dry toluene, add 8.01 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, and settle with ether after the reaction is completed. Vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(lactide) _50×4 block copolymer, the product number of which was I13. The number average molecular weight and productive rate of the obtained product are shown in Table 28.

Number-average molecular weight and reaction yield of the products obtained in table 28

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I13 20232 200 49200 188 82.1

Example 29 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _80×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off the water, add 229.14 mg of lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 4.6 mL of dry toluene, add 6.44 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, and use Diethyl ether was settled, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(lactide) _80×2 block copolymer, and the product number was D14. The number average molecular weight and productive rate of the obtained product are shown in Table 29.

Number-average molecular weight and reaction yield of the products obtained in table 29

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D14 20116 160 43400 151 83.1

Example 30 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _80×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to remove water azeotropically, and then add dihydroxyl polyethylene glycol at one end to azeotropically remove water Finally, add 455.64 mg of lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 9.2 mL of dry toluene, add 12.82 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction is completed, settle with ether. Vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(lactide) _80×4 block copolymer, the product number of which was I14. The number average molecular weight and productive rate of the obtained product are shown in Table 30.

Number-average molecular weight and reaction yield of the product obtained in table 30

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I14 20232 320 66400 314 81.6

Example 31 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _100×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 286.42 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 5.8 mL of dry toluene, add 8.06 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and vacuum dry at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _100×2 block copolymer, the product number is D15. The number average molecular weight and yield of the obtained product are shown in Table 31.

Number-average molecular weight and reaction yield of the products obtained in table 31

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D15 20116 200 49100 189 81.3

Example 32 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _100×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 569.55 mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactants in 11.4 mL of dry toluene, add 16.02 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol (Lactide) _100×4 block copolymer, the product number is I15. The number average molecular weight and yield of the obtained product are shown in Table 32.

Number-average molecular weight and reaction yield of the products obtained in table 32

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I15 20232 400 77400 394 83.5

Example 33 Preparation of Y-type polyethylene glycol monomethyl ether-poly(lactide) _150×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 429.62 mg of propylene glycol under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 8.6 mL of dry toluene, add 12.08 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(lactide) _150×2 block copolymer, the product number is D16. The number average molecular weight and yield of the obtained product are shown in Table 33.

Number-average molecular weight and reaction yield of the product obtained in table 33

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D16 20116 300 63600 291 83.2

Example 34 Preparation of dumbbell-shaped polyethylene glycol-poly(lactide) _150×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end of a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to azeotropically remove water, add 854.33mg of lactide under anhydrous and oxygen-free conditions, Dissolve the reactant in 17 mL of dry toluene, add 24.03 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction is completed, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-poly( Lactide) _150×4 block copolymer, the product ratio is I16. The number-average molecular weight and yield of the product obtained are shown in Table 34.

Number-average molecular weight and reaction yield of the products obtained in table 34

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) 1I16 20232 600 107000 592 81.4

Example 35 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _10×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 17.31 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 7.16mg (4.97×10 ^-5 mol) lactide, dissolve the reactant with 0.6mL of dry toluene, add 0.81mg of Sn(Oct) ₂ , react at 120°C for 24h, settle with ether after the reaction , dried under vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _10×2 block copolymer, and the product number is D17. The number average molecular weight and yield of the obtained product are shown in Table 35.

Number-average molecular weight and reaction yield of the products obtained in table 35

Example 36 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _10×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 34.42 mg of glycolide and 14.24 mg of lactide was dissolved in 1 mL of dry toluene, and 1.602 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24 hours to obtain a dumbbell-shaped poly Ethylene glycol-poly(glycolide 75%-lactide 25%) _10×4 block copolymer, product number I17. The number average molecular weight and yield of the obtained product are shown in Table 36.

Number-average molecular weight and reaction yield of the products obtained in table 36

Example 37 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _20×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off the water, add 34.62 mg glycolide and 14.32 mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 1 mL of dry toluene, add 1.61 mg of Sn(Oct)), and react at 120 ° C for 24 h , after the reaction was completed, it was settled with ether, and dried in vacuum at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _20×2 block copolymer, product number for D18. The number average molecular weight and yield of the obtained product are shown in Table 37.

Number-average molecular weight and reaction yield of the products obtained in table 37

Example 38 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _20×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water azeotropically, add 68.84mg of glycolide and 28.48 mg of lactide was dissolved in 2 mL of dry toluene, 3.20 mg of Sn(Oct) ₂ was added, and reacted at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polymer. Ethylene glycol-poly(glycolide 75%-lactide 25%) _20×4 block copolymer, product number I18. The number-average molecular weight and yield of the product obtained are shown in Table 38.

Number-average molecular weight and reaction yield of the products obtained in table 38

Example 39 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _30×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off water, add 51.93mg glycolide and 21.48mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 1.4mL dry toluene, add 2.42mg Sn(Oct) ₂ , and react at 120°C After 24 hours, after the reaction was completed, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _30×2 block copolymer, the product The number is D19. The number average molecular weight and yield of the obtained product are shown in Table 39.

Number-average molecular weight and reaction yield of the products obtained in table 39

Example 40 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _30×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, and then azeotropically remove water from polyethylene glycol with a single end of dihydroxyl group Finally, add 103.26 mg glycolide and 42.72 mg lactide under anhydrous and anaerobic conditions, dissolve the reactant with 3 mL of dry toluene, add 4.81 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, and the reaction ends Afterwards, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _30×4 block copolymer, and the product number was I19. The number average molecular weight and productive rate of the obtained product are shown in Table 40.

Number-average molecular weight and reaction yield of the product obtained in table 40

Example 41 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _40×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 69.24 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 28.64mg of lactide were dissolved in 2mL of dry toluene, and 3.22mg of Sn(Oct) ₂ was added to react at 120°C for 24h. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24h to obtain Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _40×2 block copolymer, the product number is D20. The number-average molecular weight and productive rate of the obtained product are shown in Table 41.

Number-average molecular weight and reaction yield of the products obtained in table 41

Example 42 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _40×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end as a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water by azeotropic, add 137.69mg of glycolide and 56.96 mg of lactide was dissolved in 3.8 mL of dry toluene, and 6.41 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and dried in vacuum at 25°C for 24 hours to obtain a dumbbell shape Polyethylene glycol-poly(glycolide 75%-lactide 25%) _40×4 block copolymer, the product code is I20. The number average molecular weight and productive rate of the obtained product are shown in Table 42.

Number-average molecular weight and reaction yield of the products obtained in table 42

Example 43 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _50×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 86.55 mg of ethyl alcohol under anhydrous and oxygen-free conditions. Lactide and 35.80mg lactide, dissolve the reactant with 2.4mL of dry toluene, add 4.03mg of Sn(Oct) ₂ , react at 120°C for 24h, settle with ether after the reaction, and dry in vacuum at 25°C for 24h. A Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _50×2 block copolymer was obtained, and the product number was D21. The number average molecular weight and productive rate of the obtained product are shown in Table 43.

Number-average molecular weight and reaction yield of the product obtained in table 43

Example 44 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _50×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 172.11 mg of glycolide and 71.20 mg of lactide was dissolved in 4.8 mL of dry toluene, and 8.01 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and dried in vacuum at 25°C for 24 hours to obtain a dumbbell shape Polyethylene glycol-poly(glycolide 75%-lactide 25%) _50×4 block copolymer, the product code is I21. The number average molecular weight and productive rate of the obtained product are shown in Table 44.

Number-average molecular weight and reaction yield of the product obtained in table 44

Example 45 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _80×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 138.48 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 57.28mg of lactide were dissolved in 4mL of dry toluene, and 6.44mg of Sn(Oct) ₂ was added to react at 120°C for 24h. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24h to obtain Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _80×2 block copolymer, the product number is D22. The number average molecular weight and productive rate of the obtained product are shown in Table 45.

Number-average molecular weight and reaction yield of the product obtained in table 45

Example 46 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _80×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water azeotropically, add 275.37mg of glycolide and 113.91 mg of lactide, dissolved the reactant in 7.8 mL of dry toluene, added 12.82 mg of Sn(Oct) ₂ , reacted at 120°C for 24 hours, settled with ether after the reaction, dried in vacuum at 25°C for 24 hours, and obtained a dumbbell shape Polyethylene glycol-poly(glycolide 75%-lactide 25%) _80×4 block copolymer, the product code is I22. The number average molecular weight and productive rate of the obtained product are shown in Table 46.

Number-average molecular weight and reaction yield of the products obtained in table 46

Example 47 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _100×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 173.10 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 71.60 mg of lactide were dissolved in 4.8 mL of dry toluene, added with 8.06 mg of Sn(Oct) ₂ , and reacted at 120°C for 24 hours. After the reaction was completed, they were settled with ether and dried in vacuum at 25°C for 24 hours. A Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _100×2 block copolymer was obtained, and the product number was D23. The number average molecular weight and productive rate of the obtained product are shown in Table 47.

Number-average molecular weight and reaction yield of the products obtained in table 47

Example 48 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _100×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water by azeotropic, add 344.22mg of glycolide and 142.39 mg of lactide was dissolved in 9.8 mL of dry toluene, and 16.02 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell shape Polyethylene glycol-poly(glycolide 75%-lactide 25%) _100×4 block copolymer, the product code is I23. The number average molecular weight and productive rate of the obtained product are shown in Table 48.

Number-average molecular weight and reaction yield of the products obtained in table 48

Example 49 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _150×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off water, add 259.65 mg glycolide and 107.41 mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 7.4 mL of dry toluene, add 12.08 mg of Sn(Oct) ₂ , and react at 120°C After 24 hours, after the reaction was completed, it was settled with ether, and vacuum-dried for 24 hours at 25°C to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 75%-lactide 25%) _150×2 block copolymer, the product The number is D24. The number average molecular weight and productive rate of the obtained product are shown in Table 49.

Number-average molecular weight and reaction yield of the products obtained in table 49

Example 50 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 75%-lactide 25%) _150×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 516.33 mg of glycolide and 213.58mg of lactide, dissolved the reactant in 14.6mL of dry toluene, added 24.03mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the reaction, dried in vacuum at 25°C for 24h, and obtained a dumbbell shape Polyethylene glycol-poly(glycolide 75%-lactide 25%) _150×4 block copolymer, the product number is I24. The number average molecular weight and productive rate of the obtained product are shown in Table 50.

Number-average molecular weight and reaction yield of the product obtained in table 50

Example 51 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _10×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 11.54 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 14.32mg of lactide were dissolved in 0.6mL of dry toluene, and 0.81mg of Sn(Oct) ₂ was added to react at 120°C for 24h. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24h. A Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _10×2 block copolymer was obtained, and the product number was D25. The number average molecular weight and productive rate of the obtained product are shown in Table 51.

Number-average molecular weight and reaction yield of the products obtained in table 51

Example 52 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _10×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 22.95 mg of glycolide and 28.48 mg) lactide, dissolved the reactant in 1 mL of dry toluene, added 1.60 mg of Sn(Oct) ₂ , reacted at 120°C for 24 hours, settled with ether after the reaction, and dried in vacuum at 25°C for 24 hours to obtain a dumbbell-shaped Polyethylene glycol-poly(glycolide 50%-lactide 50%) _10×4 block copolymer, the product number is I25. The number average molecular weight and productive rate of the obtained product are shown in Table 52.

Number-average molecular weight and reaction yield of the products obtained in table 52

Example 53 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _20×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off the water, add 23.08 mg glycolide and 28.64 mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 1 mL of dry toluene, add 1.61 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours , after the reaction was completed, it was settled with diethyl ether, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _20×2 block copolymer, product number for D26. The number average molecular weight and productive rate of the obtained product are shown in Table 53.

Number-average molecular weight and reaction yield of the products obtained in table 53

Example 54 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _20×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, and then azeotropically remove water from polyethylene glycol with a single end of dihydroxyl group Finally, add 45.90 mg glycolide and 56.96 mg lactide under anhydrous and anaerobic conditions, dissolve the reactant with 2 mL of dry toluene, add 3.20 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, and the reaction ends Afterwards, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _20×4 block copolymer, and the product number was I26. The number average molecular weight and productive rate of the obtained product are shown in Table 54.

Number-average molecular weight and reaction yield of the products obtained in table 54

Example 55 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _30×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off the water, add 34.62 mg glycolide and 42.96 mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 1.6 mL of dry toluene, add 2.42 mg of Sn(Oct) ₂ , and react at 120°C After 24 hours, after the reaction was completed, it was settled with ether, and vacuum-dried for 24 hours at 25°C to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _30×2 block copolymer, the product The designation is D27. The number average molecular weight and productive rate of the obtained product are shown in Table 55.

Number-average molecular weight and reaction yield of the product obtained in table 55

Example 56 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _30×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water azeotropically, add 68.84mg of glycolide and 85.43 mg of lactide was dissolved in 3 mL of dry toluene, and 4.81 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and dried in vacuum at 25°C for 24 hours to obtain a dumbbell-shaped poly Ethylene glycol-poly(glycolide 50%-lactide 50%) _30×4 block copolymer, product number I27. The number average molecular weight and productive rate of the obtained product are shown in Table 56.

Number-average molecular weight and reaction yield of the products obtained in table 56

Example 57 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _40×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 46.16 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 57.28mg of lactide were dissolved in 2mL of dry toluene, and 3.22mg of Sn(Oct) ₂ was added to react at 120°C for 24h. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24h to obtain Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _40×2 block copolymer, the product number is D28. The number average molecular weight and productive rate of the obtained product are shown in Table 56.

Number-average molecular weight and reaction yield of the products obtained in table 56

Example 58 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _40×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a dihydroxyl terminal, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 91.79 mg of glycolide and 113.91 mg lactide, dissolved the reactant with 4.2mL of dry toluene, added 6.41mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the reaction, dried in vacuum at 25°C for 24h, and obtained a dumbbell-shaped poly Ethylene glycol-poly(glycolide 50%-lactide 50%) _40×4 block copolymer, the product code is I28. The number average molecular weight and productive rate of the obtained product are shown in Table 58.

Number-average molecular weight and reaction yield of the products obtained in table 58

Example 59 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _50×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off water, add 57.70 mg glycolide and 71.60 mg lactide under anhydrous and oxygen-free conditions, dissolve the reactant with 2.6 mL of dry toluene, add 4.03 mg of Sn(Oct) ₂ , and react at 120°C After 24 hours, after the reaction was completed, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _50×2 block copolymer, the product The number is D29. The number average molecular weight and productive rate of the obtained product are shown in Table 59.

Number-average molecular weight and reaction yield of the products obtained in table 59

Example 60 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _50×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to azeotropically remove water, add 114.74mg of glycolide and 142.39 mg of lactide, dissolved the reactant in 5.2 mL of dry toluene, added 8.01 mg of Sn(Oct) ₂ , reacted at 120°C for 24 hours, settled with ether after the reaction, dried in vacuum at 25°C for 24 hours, and obtained a dumbbell shape Polyethylene glycol-poly(glycolide 50%-lactide 50%) _50×4 block copolymer, the product code is I29. The number average molecular weight and productive rate of the obtained product are shown in Table 60.

Number-average molecular weight and reaction yield of the product obtained in table 60

Example 61 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _80×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 92.32 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 114.57mg of lactide were dissolved in 4mL of dry toluene, and 6.44mg of Sn(Oct) ₂ was added to react at 120°C for 24h. After the reaction was completed, it was settled with ether and dried in vacuum at 25°C for 24h to obtain Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _80×2 block copolymer, the product number is D30. The number average molecular weight and productive rate of the obtained product are shown in Table 61.

Number-average molecular weight and reaction yield of the products obtained in table 61

Example 62 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _80×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end of a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to azeotropically remove water, add 183.58mg of glycolide and 227.82 mg of lactide, dissolved the reactant in 8.2 mL of dry toluene, added 12.82 mg of Sn(Oct) ₂ , reacted at 120°C for 24 hours, settled with ether after the reaction, dried in vacuum at 25°C for 24 hours, and obtained a dumbbell shape Polyethylene glycol-poly(glycolide 50%-lactide 50%) _80×4 block copolymer, the product number is I30. The number average molecular weight and productive rate of the obtained product are shown in Table 62.

Number-average molecular weight and reaction yield of the products obtained in table 62

experiment number Mn ₁ (g.mol ^-1 ) GA/LA/I Mn ₂ (g.mol ^-1 ) DP of Reaction yield (%)

GA/LA I30 20232 160/160/1 62100 153/149 81.5

Example 63 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _100×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 115.40 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 143.21mg lactide, dissolved the reactant with 5.2mL of dry toluene, added 8.06mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with diethyl ether after the reaction, and dried in vacuum at 25°C for 24h. A Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _100×2 block copolymer was obtained, and the product number was D31. The number average molecular weight and productive rate of the obtained product are shown in Table 63.

Number-average molecular weight and reaction yield of the product obtained in table 63

Example 64 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _100×4 block copolymer

Weigh 200 mg of polyethylene glycol i with dihydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 229.48 mg of glycolide and 284.78mg of lactide, dissolved the reactant in 10.2mL of dry toluene, added 16.02mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the reaction, dried in vacuum at 25°C for 24h, and obtained a dumbbell shape Polyethylene glycol-poly(glycolide 50%-lactide 50%) _100×4 block copolymer, the product number is I31. The number average molecular weight and productive rate of the obtained product are shown in Table 64.

Number-average molecular weight and reaction yield of the resulting product of table 64

experiment number Mn ₁ (g.mol ^-1 ) GA/LA/I Mn ₂ (g.mol ^-1 ) DP of GA/LA Reaction yield (%) I31 20232 200/200/1 72500 193/189 83.5

Example 65 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _150×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 173.10 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide and 214.81mg lactide, dissolved the reactant with 7.8mL of dry toluene, added 12.08mg of Sn(Oct) ₂ , reacted at 120°C for 24h, settled with ether after the reaction, and dried in vacuum at 25°C for 24h. A Y-type polyethylene glycol monomethyl ether-poly(glycolide 50%-lactide 50%) _150×2 block copolymer was obtained, and the product number was D32. The number average molecular weight and productive rate of the obtained product are shown in Table 65.

Number-average molecular weight and reaction yield of the product obtained in table 65

experiment number Mn ₁ (g.mol ^-1 ) GA/LA/I Mn ₂ (g.mol ^-1 ) DP of GA/LA Reaction yield (%) D32 20116 150/150/1 61000 139/141 80.7

Example 66 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide 50%-lactide 50%) _150×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to remove water by azeotropic, add 344.22mg of glycolide and 427.16 mg of lactide was dissolved in 15.4 mL of dry toluene, and 24.03 mg of Sn(Oct) ₂ was added to react at 120°C for 24 hours. After the reaction was completed, it was settled with ether, and vacuum-dried at 25°C for 24 hours to obtain a dumbbell shape Polyethylene glycol-poly(glycolide 50%-lactide 50%) _150×4 block copolymer, the product number is I32. The number average molecular weight and productive rate of the obtained product are shown in Table 66.

Number-average molecular weight and reaction yield of the resulting product of table 66

experiment number Mn ₁ (g.mol ^-1 ) GA/LA/I Mn ₂ (g.mol ^-1 ) DP of GA/LA Reaction yield (%) I32 20232 300/300/1 96500 291/289 81.4

Example 67 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _10×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 23.08 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 0.4 mL of dry toluene, add 0.8 mg of catalyst Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene Glycol monomethyl ether-poly(glycolide) _10×2 block copolymer, the product number is D33. The number average molecular weight and productive rate of the obtained product are shown in Table 67.

Number-average molecular weight and reaction yield of the resulting product of table 67

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D33 20116 20 22600 18 84.7

Example 68 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _10×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to remove water by azeotropy, then add 45.90 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 1 mL of dry toluene, add 1.6 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction is completed, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-poly( Glycolide) _10×4 block copolymer, the product number is I33. The number average molecular weight and productive rate of the obtained product are shown in Table 68.

Number-average molecular weight and reaction yield of the resulting product of table 68

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I33 20232 40 25100 35 80.2

Example 69 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _20×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 46.16 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant in 1 mL of dry toluene, add 1.61 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Monomethyl ether-poly(glycolide) _20×2 block copolymer, the product number is D34. The number average molecular weight and productive rate of the obtained product are shown in Table 69.

Number-average molecular weight and reaction yield of the resulting product of table 69

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D34 20116 40 25200 37 82.6

Example 70 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _20×4 block copolymer

Weigh 200mg of polyethylene glycol i with a single end being a dihydroxyl group, put it into a dry reaction bottle with a branch, add 20mL of toluene to azeotropically remove water, add 91.79mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 1.8 mL of dry toluene, add 3.20 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol. (Glycolide) _20×4 block copolymer, the product number is . The number average molecular weight and productive rate of the obtained product are shown in Table 70.

Number-average molecular weight and reaction yield of the product obtained in table 70

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I34 20232 80 31200 75 81.4

Example 71 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _30×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 69.24 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 1.4 mL of dry toluene, add 2.42 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(glycolide) _30×2 block copolymer, the product number is D35. The number average molecular weight and yield of the obtained product are shown in Table 71.

Number-average molecular weight and reaction yield of the products obtained in table 71

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D35 20116 60 27900 56 81.6

Example 72 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _30×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of a dihydroxy group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 137.69 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 2.8 mL of dry toluene, add 4.81 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol (Glycolide) _30×4 block copolymer, the product number is I35. The number average molecular weight and yield of the obtained product are shown in Table 72.

Number-average molecular weight and reaction yield of the products obtained in table 72

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I35 20232 120 34500 115 82.6

Example 73 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _40×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of double hydroxyl, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, dihydroxy polyethylene glycol monomethyl ether toluene After boiling off the water, add 92.32 mg of glycolide under anhydrous and oxygen-free conditions, dissolve the reactant with 1.8 mL of dry toluene, add 3.22 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, and use Diethyl ether was settled, and vacuum-dried at 25°C for 24 hours to obtain a Y-type polyethylene glycol monomethyl ether-poly(glycolide) _40×2 block copolymer, and the product number was D36. The number average molecular weight and yield of the obtained product are shown in Table 73.

Number-average molecular weight and reaction yield of the products obtained in table 73

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D36 20116 80 31200 72 80.4

Example 74 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _40×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of dihydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, and then azeotropically remove water from polyethylene glycol with a single end of dihydroxyl group Finally, add 183.58 mg of glycolide under anhydrous and oxygen-free conditions, dissolve the reactant with 3.6 mL of dry toluene, add 6.41 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction, settle with ether, Vacuum-dried at 25°C for 24 hours to obtain a dumbbell-shaped polyethylene glycol-poly(glycolide) _40×4 block copolymer, the product number of which was I36. The number average molecular weight and yield of the obtained product are shown in Table 74.

Number-average molecular weight and reaction yield of the products obtained in table 74

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I36 20232 160 38600 149 80.3

Example 75 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _50×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a single end of a double hydroxyl group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 115.40 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 2.4 mL of dry toluene, add 4.03 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(glycolide) _50×2 block copolymer, the product number is D37. The number average molecular weight and yield of the obtained product are shown in Table 75.

Number-average molecular weight and reaction yield of the product obtained in table 75

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D37 20116 100 31900 93 83.1

Example 76 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _50×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 229.48 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 4.6 mL of dry toluene, add 8.01 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol. (Glycolide) _50×4 block copolymer, the product number is I37. The number average molecular weight and yield of the obtained product are shown in Table 76.

Number-average molecular weight and reaction yield of the products obtained in table 76

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I37 20232 200 43500 189 82.1

Example 77 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _80×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 184.64 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 3.6 mL of dry toluene, add 6.44 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and vacuum dry at 25°C for 24 hours to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(glycolide) _80×2 block copolymer, the product number is D38. The number average molecular weight and yield of the obtained product are shown in Table 77.

Number-average molecular weight and reaction yield of the products obtained in table 77

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D38 20116 160 39200 153 84.5

Example 78 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _80×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to remove water azeotropically, then add 367.16 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 7.4 mL of dry toluene, add 12.82 mg of Sn(Oct) ₂ , and react at 120°C for 24 hours. After the reaction, settle with ether and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol. (Glycolide) _80×4 block copolymer, the product number is I38. The number average molecular weight and yield of the obtained product are shown in Table 78.

Number-average molecular weight and reaction yield of the products obtained in table 78

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I38 20232 320 57200 311 83.5

Example 79 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _100×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 230.80 mg of ethyl ether under anhydrous and oxygen-free conditions. Lactide, dissolve the reactant with 4.6mL of dry toluene, add 8.06mg of Sn(Oct) ₂ , react at 120°C for 24h, settle with ether after the reaction, and vacuum dry at 25°C for 24h to obtain Y-type polyethylene glycol Alcohol monomethyl ether-poly(glycolide) _100×2 block copolymer, the product number is D39. The number average molecular weight and yield of the obtained product are shown in Table 79.

Number-average molecular weight and reaction yield of the products obtained in table 79

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D39 20116 200 45000 188 82.3

Example 80 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _100×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 458.96 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 9.2 mL of dry toluene, add 16.02 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol (Glycolide) _100×4 block copolymer, the product number is I39. The number average molecular weight and productive rate of the obtained product are shown in Table 80.

Number-average molecular weight and reaction yield of the product obtained in table 80

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I39 20232 400 66700 389 81.7

Example 81 Preparation of Y-type polyethylene glycol monomethyl ether-poly(glycolide) _150×2 block copolymer

Weigh 200 mg of polyethylene glycol monomethyl ether d with a double hydroxyl at one end, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, then add 346.20 mg of ethyl ether under anhydrous and oxygen-free conditions. For lactide, dissolve the reactant with 7 mL of dry toluene, add 12.08 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain Y-type polyethylene glycol Monomethyl ether-poly(glycolide) _150×2 block copolymer, the product number is D40. The number average molecular weight and yield of the obtained product are shown in Table 81.

Number-average molecular weight and reaction yield of the products obtained in table 81

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) D40 20116 300 55100 292 81.6

Example 82 Preparation of dumbbell-shaped polyethylene glycol-poly(glycolide) _150×4 block copolymer

Weigh 200 mg of polyethylene glycol i with a single end of a dihydroxy group, put it into a dry reaction bottle with a branch, add 20 mL of toluene to azeotropically remove water, add 688.43 mg of glycolide under anhydrous and oxygen-free conditions, Dissolve the reactant in 13.8 mL of dry toluene, add 24.03 mg of Sn(Oct) ₂ , react at 120°C for 24 hours, settle with ether after the reaction, and dry in vacuum at 25°C for 24 hours to obtain dumbbell-shaped polyethylene glycol-polyethylene glycol (Glycolide) _150×4 block copolymer, the product number is I40. The number average molecular weight and yield of the obtained product are shown in Table 82.

Number-average molecular weight and reaction yield of the products obtained in table 82

experiment number Mn ₁ (g.mol ^-1 ) A/I Mn ₂ (g.mol ^-1 ) DP Reaction yield (%) I40 20232 600 89600 588 83.6

In the above table, Mn ₁ is the number-average molecular weight of polyethylene glycol with a single-end dihydroxyl group, A/I is the molar ratio of glycolide and initiator; Mn ₂ is the dumbbell-shaped polyethylene glycol and polyglycolide embedded The number-average molecular weight of the block copolymer is determined by ¹ H NMR; DP is the average degree of polymerization of the GA structural unit of the dumbbell-shaped polyethylene glycol and polyglycolide block copolymer obtained from the number-average molecular weight.

The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention will not be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (10)

1. A block copolymer with a structure as shown in formula (I):

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150. 2. the preparation method of block copolymer described in claim 1, comprises: Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol monomethyl ether with a double hydroxyl at one end initiates copolymerization of glycolide and lactide in an organic solvent, and the reaction temperature of the copolymerization is 100 °C to 130 °C, a block copolymer with the structure shown in formula (I) is obtained:

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150. 3. preparation method according to claim 2, is characterized in that, described single end is the polyethylene glycol monomethyl ether of dihydroxyl according to the following method preparation: Under stirring, polyethylene glycol monomethyl ether, acetone acetal 2,2,-bis(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol were mixed in an organic solvent to obtain acetone condensation-protected bis Hydroxy polyethylene glycol monomethyl ether; Under the condition that the pH value is 3-4, the acetone condensation-protected dihydroxy polyethylene glycol monomethyl ether is deprotected by using a cation exchange resin to obtain polyethylene glycol monomethyl ether with a single end of a dihydroxy group. 4. preparation method according to claim 2, is characterized in that, described polyoxyethylene glycol monomethyl ether, acetone 2,2,-two (hydroxymethyl) propionic anhydride and 4-dimethylaminopyridine mol ratio It is 1:(2~4):(0.5~1.5). 5. The preparation method according to claim 2, characterized in that the number average molecular weight of the polyethylene glycol monomethyl ether is 1000-40000. 6. A block copolymer with a structure as shown in formula (II):

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150. 7. the preparation method of block copolymer described in claim 6, comprises: Under anhydrous and oxygen-free conditions, using stannous octoate as a catalyst, polyethylene glycol with a single end of a double hydroxyl group initiates the copolymerization of glycolide and lactide in an organic solvent, and the reaction temperature of the copolymerization is 100 ° C ~ 130 ° C °C, the block copolymer represented by the structural formula (II) is obtained:

Among them, 10≤n≤1500, 10≤x≤150, 10≤y≤150. 8. preparation method according to claim 7, is characterized in that, described single-end is the polyethylene glycol of dihydroxyl group and is prepared according to the following method: Under stirring, polyethylene glycol, acetone acetal 2,2,-di(hydroxymethyl)propionic anhydride, 4-dimethylaminopyridine and methanol are mixed in an organic solvent to obtain acetone condensation-protected bishydroxypolyethylene diol; Under the condition that the pH value is 3-4, the acetone condensation-protected dihydroxypolyethylene glycol is deprotected by using a cation exchange resin to obtain the polyethylene glycol with a single terminal of a dihydroxyl group. 9. preparation method according to claim 8, is characterized in that, described polyethylene glycol, acetone acetal 2,2,-two (hydroxymethyl) propionic anhydride and 4-dimethylaminopyridine mol ratio are 1: (5~7): (1.5~2). 10. The preparation method according to claim 7, characterized in that the number average molecular weight of the polyethylene glycol is 1000-40000.

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