WO2004000376A1

WO2004000376A1 - Biodegradable and bioabsorbable materials for medical use and process for producing the same

Info

Publication number: WO2004000376A1
Application number: PCT/JP2002/006330
Authority: WO
Inventors: Hiroyuki Shirahama; Masamitsu Miyazaki; Mikio Hukuchi
Original assignee: Goodman Co., Ltd
Priority date: 2002-06-25
Filing date: 2002-06-25
Publication date: 2003-12-31
Also published as: JPWO2004000376A1; KR20050013186A; CA2428640A1

Abstract

Bioabsorbable polymers employed as medical materials such as vascular stents and sutures have almost constant dynamic properties (tensile strength, etc.) and degradation speed due to absorption. In case of improving these dynamic properties, then these materials become fragile and the degradation speed is lowered. In case of elevating the degradation speed, then the dynamic properties are worsened and, as a result, there arises a problem that the purpose and site of using are restricted. Under these circumstances, a bioabsorbable polymer is copolymerized with a cyclic depsipeptide to give a copolymer having the ring-opening copolymerized depsipeptide. Thus, the dynamic properties and degradation speed can be controlled depending on the content of the depsipeptide.

Description

Description Biodegradable bioabsorbable material for medical use and manufacturing method thereof

The present invention relates to a medical biodegradable polymer that can be used as a biodegradable bioabsorbable material tool such as a suture, a vascular stent, a carrier for living cells, a carrier for drugs, and the like. The present invention relates to a bioabsorbable material and a method for producing the same. Background art

Examples of bioabsorbable polymers used as medical materials such as vascular stent composites include polylactic acid, polydaricholic acid, and polydactin, polydioxanone, and polyglyconate, which are copolymers of both, (trimethylene glycol). And copolymers of polycarbonate and glycolide).

Such bioabsorbable polymers are widely used because they are decomposed and absorbed in the living body, but their mechanical properties such as tensile strength and the decomposition rate for absorption are almost fixed. However, when its mechanical properties are increased, it becomes brittle and the decomposition rate becomes slow. In addition, the mechanical properties decrease when the decomposition speed is increased. Therefore, there is a problem that the purpose of use and the place of use are limited. Disclosure of the invention

The present invention provides a copolymer obtained by copolymerizing a bioabsorbable polymer and a cyclic peptide to form a ring-opening copolymer of the derivative, whereby the mechanical properties and the degradation rate are adjusted by the content of the depsipeptide. To prevent inflammation and other problems. A biodegradable bioabsorbable material for medical use made of a high yield polymer.

The amount of the depsipeptide added is generally about 2% to 60% in molar ratio.If it is less than 2%, the effect of the addition is not obtained, and if it is more than 60%, the mechanical properties are excessively reduced. Because it becomes. However, there are many types of bioabsorbable polymers that can be used, and in the case of copolymer bioabsorbable polymers, the addition limit of debseptid is effective depending on the blending amount and addition amount other than the above. In some cases, the above addition ratio is not a confirmed value. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a structural diagram of a depsipeptide, FIG. 2 is a structural diagram of a terpolymer having a depsipeptide unit, and FIG. 3 is a structural diagram illustrating the synthesis of depsipeptide. 4 is a structural diagram of a terpolymer obtained by ring-opening copolymerization of a depsipeptide, FIG. 5 is a graph showing a ¹ H NMR spectrum of the terpolymer, and FIG. 6 contains only a buffer solution FIG. 7 is a graph showing the results of a hydrolysis test using a digestion solution, and FIG. 7 is a graph showing the results of the enzymatic degradation characteristics of a terpolymer and each homopolymer by proteinase K. FIG. 9 is a graph showing the degradation characteristics of the copolymer, FIG. 9 is a graph showing the relationship between the amount of depsipeptide and the degradation rate, and FIG. 10 is a graph showing the synthesis conditions of each copolymer and homopolymer, the polymer yield, Molecular weight Fig. 11 is a chart showing the thermal properties of the terpolymer and each homopolymer. Fig. 12 is a chart showing the mechanical properties (tensile properties) and thermal properties of the terpolymer. Fig. 13 is a chart showing the change in various physical properties of the terpolymer before and after degradation by the proteinase K. Fig. 14 is a chart showing the amount of debpeptide and the thermal properties. It is a chart showing a relationship. BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be described in more detail with reference to the accompanying drawings.

Figure 1 shows the structure of the debpeptide.

As shown in the figure, the side chain R group is an alkyl group such as a methyl group, an isopropyl group and an isobutyl group, and the side chain R 'group is an alkyl group such as a methyl group and an ethyl group.

Examples of debutipides are debutipeptide synthesized from an amino acid and a hydroxy acid derivative, and hydroxy acid derivatives are cloguchi cetyl chloride, 2-bromopropionyl bromide and 2-bromo-n-butyryl bromide. And the obtained depsipeptides are referred to as L-MM〇, L-DMO, and L-MEMO, respectively, in the order of the hydroxy acid derivatives, and all of them are applicable to the present invention. The enzymatic degradability of the copolymer by peptide monomer and ε-caprolactone (CL) as a bioabsorbable polymer is determined by proteinase degradation as L-MMO / CL> L-DMO / CL〉 L-MEMO The order is / CL.

In addition, depsipeptide synthesized from an amino acid and an oxyacid derivative uses L-alanine, L- (DL- or D-) norin and L-leucine as amino acids, and converts the resulting depsipeptide to amino acid. In this order, DMO, PM に従い, and BMO, respectively, are all applicable to the present invention, but the enzymatic degradation of the copolymer by these depsipeptide monomers and ε-force prolacton (CL) is the same as that of proteinase. For zeolysis, DMΚ / CL> PMOZCL≥BMOZC L, and for cholesterol esterase, PMOZC L> BMOZC L≥DMOZC L. Example of the first embodiment

Cyclic depsipeptide (DMO) was added to a copolymer of L-lactide (L-LA), a raw material of polylactic acid, and ε-caprolactone (CL), a raw material of polyε-caprolactone 3 It was an original copolymer.

FIG. 2 is a structural diagram of a copolymer having a peptide unit obtained by polymerizing the debut peptide. U indicates a debut peptide unit.

Therefore, 3,6-dimethyl-2,5-morpholinedione (DMO) was synthesized as a cyclic depsipeptide. The cyclic depsipeptide is a cyclic ester amide comprising an α-amino acid and an α-hydroxy acid derivative. Here, << L-alanine was used as the amino acid, and DL-2-bromopropionyl bromide, a hydroxy-acid derivative, was used.

In the first step of the synthesis, first, Schotten'-Baum ann reaction between alanine and 2-bromopropionyl bromide was carried out in an aqueous alkaline solution, and the peptide was bonded to obtain 2-bromopropionylalanine (Fig. 3).

That is, after cooling 150 ml of an aqueous solution of DL-alanine (53.4 g, 0.6 mo 1) to about 5 ° C, a 4 NN a 0 H (0.6 mo 1) aqueous solution was added to 4 NN a 0 H (0.72 mo 1) 180 ml and DL-2 -bromopropionyl bromide (0.66 mo 1) 69.9 m 1 alternately with cooling and stirring in an ice bath Over about 30 minutes. The reaction mixture was always kept slightly alkaline. After the completion of the reaction, a white product was separated by filtration.

The product was dissolved in water and 5N HCl was added dropwise so that the pH was about 3, then the water was removed by evaporation. The remaining aqueous solution was slowly acidified with 5 NHC 1 while cooling to give more white product. These resulting white products are The product was purified by soxhlet extraction using ether.

Yield 30 ~. ^{^; 1 !! NMR (δ,} CD C 1 3) 1. 5 4 (d, 3 H, NHCHCH 3), 1. 9 1 (d, 3 H, B r CH CH 3), 4. 4 5 ( q, 1 H, NHCH CH ₃ ), 4.59 (q, 1 H, Br CHCH ₃ ), 6.88 (brs, 1 H, NH).

Subsequently, purified 2 - Buromopuropio two Ruaranin (1 9. 7 g, 0. 0 8 8 1 mo 1) between this and equimolar N AHC_〇 _{3 (7. 4 0 g, 0.} 0 8 8 1 mo 1) was added to 150 ml of dimethylformamide (DMF), and refluxed at 60 ° C for 24 hours to effect intramolecular cyclization and desalting to obtain DMO as a cyclic depsipeptide as a white powder. (Figure 3

DMO was purified by recrystallization twice from black-mouthed form.

Yield 40-60%; mp 158-159 ° C; ¹ !! NMR (δ

, CDC ") 1. 5 4 ( d, 3 H, NHCHCH 3), 1. 6 2 (d, 3 H, 〇 _{CHCH 3), 4. 24 (q} , 1 H, NHCH), 4. 9 1 ( q

, 1H, 〇CH), 7.07 ppm (brs, 1H, NH).

Next, the synthesis of the terpolymer will be described.

Among the copolymerized monomers, cyclic depsipeptide (L-DMO) was synthesized from -amino acid (L-alanine) and α-hydroxy acid derivative (DL-2-bromopropionylpromide) and then purified.

Further, after lactone (CL) is dried for 48 hours by dissolution after C a H ₂ in toluene and vacuum distilled (2 times), L - lactide (L - LA) after recrystallization from TH F, All polymerization operations purified by sublimation (twice) were performed under an argon atmosphere.

Figure 4 shows the synthesis scheme of the L-DMO / CL / L-LA terpolymer. Preparation of the copolymer was performed as follows.

A predetermined amount of both L-DMO and L-LA monomers dissolved in THF and a toluene solution of tin (II) octylate {Sn (0ct) 2; 0.2 mol% Zmonomer} as a catalyst Into a Schlenk tube (polymerization vessel), and trap and remove the solvent THF and toluene under reduced pressure. Next, a predetermined amount of the CL monomer is placed in the same polymerization vessel, and the vessel is sealed. After a predetermined time (12 hours) when the sealed vessel was immersed in an oil bath at 120 ° C. to start polymerization, the polymerization vessel was taken out of the oil bath and cooled. The resulting crude polymer was dissolved in chloroform and purified by reprecipitation (twice) in methanol. Figure 10 shows the synthesis conditions for each copolymer and homopolymer, and the yield and molecular weight of the resulting polymer.

Furthermore, L - DMO / CL / L - LA (= 8: 1 3: 7 9) 3 Mototomokasane ¹ H NMR de Isseki coalescing (δ, CD C 1 ₃₎ are as follows.

1.38 (m, 2 H, CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ ), 1.50 (m, 6 H, CH ₃ X 2 (L-DMO)), 1.57 (d, 6 H, CH ₃ X 2 (L-LA)), 1.68 (m, 4 H, CH ₂ CH ₂ CH ₂ CH 2 CH ₂ ), 2.25 to 2.45 (splittingint wo eaks, 2 H, C CH ₂ ), 4.60 (m, 1 H, OCH (L-D MO)), 5.17 (q, 3 H, OCHX 2 (L-LA), NH CH (L- DMO)), 6.60 ppm (br.m, 1H, NH).

Next, various physical properties of the polymer will be described.

The composition of the copolymer was determined from the peak integral ratio of the ¹ H NMR spectrum measured using a nuclear magnetic resonance apparatus at 400 MHZ (JEOLJ MN-LA 400). In addition, the chain sequence (randomness) of the copolymer was estimated from these spectra. The number average molecular weight (M _n ) and molecular weight distribution (MwZMn) of the polymer are GPC 800 system manufactured by Toso Corporation {Column: TSK gel (G 200 H _HR + G 300 H _HR) + G 4 0 0 H + _R + G 5 0 0 0 H _HR ), power column temperature 40 ° C, differential refractive index (RI) detector}, and determined from a calibration curve made with standard polystyrene. The eluent used was a chromatographic form, and the flow rate was 1 mL min ¹ .

The thermal properties of the polymer, namely the glass transition temperature (T _g ), melting point (T _m ) and heat of fusion (ΔΗπι) were determined using a differential scanning calorimeter SSC 5100 DSC 22 C manufactured by Seiko Instruments Inc. It was measured. The measurement was performed in a nitrogen atmosphere at a heating rate of 10 ° C / mi η. The randomness of the copolymer was also estimated from these thermal properties.

The mechanical properties (tensile strength and elongation at break) of the polymer were measured at a crosshead speed of 50 mm / min using a tensile tester RTC-121OA manufactured by Orientec Co., Ltd. The measurement was performed at least three times and the average value was used. The dumbbell specimen (parallel length x width x thickness = 12 x 2.65 x 1.46 mm) of a polymer sample was prepared by mixing the polymer material at 180 to 200 ° C. It was produced by heating and pressing for 5 minutes.

Next, the enzymatic degradation test of the polymer will be described.

The enzymatic degradation test was performed in the same manner as before, but the outline is shown below.

A polymer tube (thickness: approx. 100 ^ m, number: 10 mg) enclosed in a polyethylene sheet mesh (mesh: approx. IX lmm) is placed in a sample vial containing enzyme and buffer (50 ml). Degradation was performed by incubating at 37 ° C. The enzyme concentration was 1 international unit (IU) per mg of polymer sample.

The enzyme-containing buffer solution (decomposed solution) was replaced with a new decomposed solution approximately every 40 hours in consideration of the decrease in oxygen activity and the contamination and growth of microorganisms in the air. Degradability was evaluated based on changes in polymer weight and physical properties (molecular weight, composition, thermal properties) before and after decomposition. Proteinase K (derived from Tritirachiuma 1 bum, manufactured by Wako Pure Chemical Industries, Ltd., having an activity of 20 I UZmg), which is a kind of protease, is used as a buffer for Tridine (pH). 8.0) was used.

FIG. 10 shows the results of polymerization of the L-DMO / CL / L-LA terpolymer and each homopolymer obtained from the above test.

In the case of the CL and L-LA homopolymers {po 1 y (CL), po 1 y (L-LA)}, respectively, a high molecular weight and high yield of the polymer was obtained, but the L-DM〇 homopolymer {poly (L-DMO)} was obtained only with low yield and low molecular weight. This is thought to be the result of the resulting depolymer peptide being prone to transesterification with its monomer (here, L-DMO) or oligomer or a back-biting reaction that causes molecular chain scission. Can be

On the other hand, in the case of a terpolymer, the copolymer composition indicates that the reactivity of L-LA is high under the copolymerization conditions.

In addition, since L-DMO is more incorporated into the copolymer than CL ', the reactivity is not lower than that of CL. Therefore, the reason why the above-mentioned L-DMM homopolymer is low in molecular weight / yield is also due to its susceptibility to ester exchange. The molecular weight and yield of the copolymers are relatively good, but their values gradually decrease with increasing L-DMO content. This also supports the above considerations.

FIG. 11 shows the thermal characteristics of the obtained terpolymer and each homopolymer.

As reported conventionally, P 0 1 y (CL) is T _g, T _m pixels respectively located in flexibility about a 6 0 and 6 0 ° C, but a low melting crystalline polymers one , Poly (L-LA) have T _g and T _m of about 60 and It is a hard, brittle crystalline polymer with a high melting point of 180 ° C, and poly (L-DMO) is an amorphous glass-like polymer.

In the case of the terpolymer, only one T g and one Tm were observed, and their values also changed with the composition, suggesting a strong randomness. Considering the balance between tensile strength and elongation (softness) at, it is considered appropriate that the exact value is around 35 ° C.

FIG. 5 shows the ¹ H NMR spectrum of the L-DMOZC LZL-LA (8:13:79) terpolymer. This figure also confirms that the terpolymer is random. That is, the α- and ε-methylene proton peaks (f, i) in the CL unit are sensitive to adjacent comonomer units, and each of these peaks is split into two (the high f, i The peak on the magnetic field side corresponds to the homosequence of CL-CL, and the peak on the low and high magnetic field side corresponds to the peak based on the heterosequence of L-LA-CL and L-DM〇-CL.) The polymer was found to be a random copolymer.

In addition, in copolymerization at 120 ° C lower than the Tm of L-DMO (about 170 ° C), this unit is accurately introduced into the copolymer because of the high reactivity of L-LA This is because polymerization of (Tm is about 95 ° C.) occurs first, and L-DMO (and / or CL) is ring-opened by this active growing end and is randomly incorporated into the copolymer.

Figure 12 shows the mechanical properties (tensile properties) and thermal properties of the terpolymer.

The terpolymer in the figure was newly synthesized on a large scale to measure these physical properties. (Mainly synthesized by changing the amount of CL in order to improve the flexibility of the polymer.) All with a molecular weight (M _n ) of 100,000 or more (100.2 to 158,000) To the physical properties The effect of the molecular weight on this need not be taken into account much.

First, the tensile properties show that the strength decreases as the CL content increases, that is, decreases as the L-LA content decreases, but the elongation increases sharply when the CL content is 20 m 0 1% or more, and the flexibility of the copolymer increases. _Q that shows improvement

The tensile strength of these terpolymers is higher than that of general-purpose plastic, polyethylene (PE), and is higher than that of polypropylene (PP). In addition, it has a higher tensile strength than biodegradable plastics such as bionole (Bolibutylene succinate (PBSU), manufactured by Showa Polymer Co., Ltd.) and Biopol CP (3HB-c0-3HV), manufactured by Nippon Monsanto Co., Ltd.) The strength is great.

The elongation at break was much larger in samples with a CL content of 20 mol 1% or more than in bioballs, and was equal to or greater than that of PE, PP and bionore.

On the other hand, the thermal properties of the terpolymer are Tm, Δ

Was reduced with the increase in both CL of H _m, it can be seen that both are T _m 1 0 0 or more ° C crystalline polymer scratch.

Judging from these mechanical and thermal properties, the L-DMO / CL / L-LA (4:20:76) terpolymer having a CL content of 20 mo 1% or more (T _g = 3 4.3 ° C) is a good balance of physical properties.

Next, before examining the enzymatic degradability, a hydrolysis test using a decomposed solution containing only a buffer was performed (Fig. 6). L-DMO homopolymer was not used in the degradation test because it shows water solubility. As can be seen from the figure, the hydrolyzability decreases with an increase in the amount of CL units, and conversely increases with an increase in the amount of L-DM0 units. Therefore, the hydrophobicity increases in the order of L-DMO and L-LA <CL unit. However, even for the ternary copolymer showing the maximum, the weight loss after 200 hours is about 10%. Figure 7 shows the oxygen degradability of the terpolymer and each homopolymer by proteinase K.

In the case of a homopolymer, poly (L-LA) is decomposed to some extent, while P ly (CL), which is more decomposable from the viewpoint of thermal properties, shows almost weight loss within 200 hours. Did not. This present enzyme poly mer {Lac Bok I le groups here having an alkyl chain length is short and the side chains between ester bonds [- 〇 _{- CH (CH 3) - CO} - ] that have a po 1 y (L-LA)}, but the ethylene chain between the ester bonds is relatively linear and relatively long p 0 1 y (It seems that CD has no specificity. In the case of the co-polymer, the degradability increases greatly with the increase of the L-DMO unit content as compared with P o 1 y (L-LA). One of the major factors is that the L-DMO unit that has it also shows substrate specificity.

Another possible cause is that the molecular weight (Mn) and thermal properties (Tm, ΔHm) of the terpolymer are lower than that of poly (L-LA) (Fig. 11). ).

In any case, the L-DMOZC LZL-LA terpolymer has improved enzymatic degradation by proteinase K while relatively maintaining the thermal and mechanical properties of po 1 y (L-LA) .

Then, to estimate the mechanism of degradation by enzymes, L-DMO

Changes in various physical properties of the ZC LZL-LA (8: 8: 84) terpolymer before and after degradation by the proteinase K were examined (Fig. 13).

As can be seen from Fig. 13, as the decomposition progressed, the L-DMO unit content in the residual polymer decreased significantly. As described above, this enzyme has substrate specificity for both L-LA and L-DMO units.However, since the polymer domain containing L-LA unit is crystalline, -Amorphous hydrophilic part containing a lot of DMO unit It is considered that the degradability increased and the composition ratio decreased.

In addition, the amount of the CL unit that was hardly degraded also decreased, suggesting that the CL unit was present next to the L-DM unit, and that the ester bond between the two was cleaved by the enzyme. Is done. The molecular weight (M _n ) of volima decreased with the progress of decomposition, and its distribution (M w ZM n) showed a tendency to spread. Therefore, it can be said that the degradation by this enzyme proceeds randomly from inside the polymer film.

In addition, the thermal properties (T _m , ΔH m) of the polymer increase with the progress of decomposition. Therefore, as described above, the decomposition of the amorphous hydrophilic part containing a large amount of L-DMO unit has priority. Then you can see what happens.

The obtained copolymer was found to be a random copolymer from the results of NMR (nuclear magnetic resonance measurement) and thermal properties measurement.

This shows that the addition of the depsipeptide dramatically increased the decomposition rate without losing the mechanical strength and flexibility.

FIG. 7 shows the enzymatic degradation characteristics of the copolymer having the depsipeptide unit.

In the above description, lactide was described as L-lactide, but L-lactide and its enantiomer, D-lactide, are combined and polymerized to form a stereocomplex, which results in heat such as melting point. Target characteristics can be improved.

In addition, free forming ability can be imparted by changing the glass transition temperature.

Therefore, instead of the tertiary copolymer as described above, a binary copolymer in which depsipeptide and L-lactide are copolymerized to form a ring-opening polymer of depsipeptide may be used. L-lactide and its enantiomer, D-lactide, are combined and copolymerized to form a stereocomplex lactide to form debutiptide. It may be a stereocomplex of a ring-opened copolymer. Example of the second embodiment

Fig. 1 shows the structure of a copolymer having a peptide unit when copolymerized with ε-force prolactone, a raw material of poly _ε -force prolactone, to obtain a copolymer in which ring opening polymerization of debutpeptide is obtained. See Figure 2. U indicates a deb-type dump.

According to this, as in the case of the first embodiment, mechanical strength is imparted, and the decomposition rate is increased.

Here, in order to know the effect of depsipeptide units in a copolymer having a peptide unit, the side chain R group in debutpeptide was changed to a methyl group, an isopropyl group, and an isobutyl group, and the effect was examined. did. FIG. 8 shows the decomposition characteristics of the copolymer having debutpeptide.

According to this, the decomposition characteristics are in the order of methyl group >> isopropyl group> isobutyl group, and it can be seen that the decomposability decreased as the bulk of the side chain increased. . Third Embodiment

Using 3-isopropyl-6-methyl-2.5-morpholinedione (Ρ Μ として) as depsipeptide, it was copolymerized with poly ε-force prolactone to obtain a copolymer in which debutpeptide was ring-opened. .

Therefore, the change in thermal characteristics and decomposition rate when the amount of debutiptide was changed was examined.

Fig. 14 shows the relationship between the thermal characteristics and Fig. 9 shows the relationship between the decomposition rates.

According to this, the glass transition temperature (Τ _g ) increases as the amount of depsipeptide increases, and the melting point (T m) and heat of fusion (AH m) are observed when the ε-force prolactone amount is less than 20 m 0 1%. And have crystallinity Was.

The decomposition rate increased with the increase in the amount of debutpeptide.

In the description of each of the above embodiments, poly-ε-force prolactone and polylactic acid have been described as examples of bioabsorbable polymers. However, the present invention is not limited to these. The polymer may be a polymer, for example, boridioxanone, trimethylene carbonate, and a copolymer of two or more thereof. Industrial applicability

According to the present invention described in detail above, a bioabsorbable polymer is copolymerized with a cyclic peptide to form a copolymer having debutitunitite, whereby the mechanical properties and the degradation properties are adjusted for a medical product. This has the effect of making it a degradable bioabsorbable material.

Further, modification of the peptide unit with an alkyl group has the effect of adjusting the mechanical properties and the decomposition properties.

Claims

The scope of the claims

1. A biodegradable bioabsorbable material for medical use, which is a copolymer obtained by copolymerizing a bioabsorbable polymer and a cyclic peptide and then opening the copolymer to form a ring-opening copolymer.

2. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the amount of the depsipeptide added is 2 to 60%.

3. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the bioabsorbable polymer is force prolactone.

4. The biodegradable bioabsorbable material for medical use according to claim 1 or 3, wherein the debupeptide is a cyclic depsipeptide, and the force prolacton is ε-force prolactone.

5. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the bioabsorbable polymer is lactide.

6. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the depsipeptide is a cyclic depsipeptide, and lactide is L-lactide.

7. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the depsipeptide is a cyclic depsipeptide and the lactide is a stereocomplex of L-lactide and D-lactide.

8. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the bioabsorbable polymer is obtained by copolymerizing force prolactone and lactide.

9. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the biodegradation rate is adjusted by changing the ratio of the depsipeptide to the bioabsorbable polymer. ·

10. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the R group in the side chain of the cyclic depsipeptide is an alkyl group.

1 1. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the side chain R 'group of the cyclic depsipeptide is an alkyl group.

1 2. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the side chain R group of the cyclic depsipeptide is a methyl group.

1 3. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the side chain R group of the cyclic depsipeptide is an isopropyl group.

1 4. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the R group in the side chain of the cyclic depsipeptide is an isobutyl group.

1 5. The biodegradable bioabsorbable material for medical use according to claim 1, wherein the side chain R 'group of the cyclic depsipeptide is a methyl group.

1 6. The method according to claim 1, wherein the side chain R ′ group of the cyclic depsipeptide is ethyl. A biodegradable bioabsorbable material for medical use, comprising:

17. A method for producing a biodegradable bioabsorbable material for medical use, wherein a ring opening reaction of depsipeptide is performed when a bioabsorbable polymer and a cyclic depsipeptide are copolymerized.