JPH082955B2 - Block copolymer and method for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a block copolymer containing polylactic acid as a main component, which is suitable for medical surgery, particularly biodegradable films and fibers, and a method for producing the same. .

[Conventional technology and problems]

Resins such as polylactic acid, polyglycolic acid, and lactic acid-glycolic acid copolymer are widely applied as bioabsorbable polymers because they are hydrolyzed in the body and safely absorbed. For example, Japanese Patent Publication No. 41-2734 discloses an absorbable surgical fiber product made of polylactic acid and a method for producing the same.

However, films and fibers made of these resins are poor in flexibility, and for example, when making a monofilament-like suture having a diameter of about 1 mm or more, sufficient flexibility cannot be obtained, and it is used as a surgical suture. Is inappropriate.

In order to overcome this drawback, JP-A-59-100130 discloses a polyglycolic acid-polyoxyalkylene triblock copolymer. This copolymer is obtained by subjecting glycolide (cyclic dimer of glycolic acid) to ring-opening polymerization using polyoxyalkylene having a hydroxy terminal as an initiator. However, the inventors of the present invention conducted a careful follow-up test and found that the obtained copolymer had a glycolic acid chain, which is a very hard structure. I couldn't say that. In addition, this copolymer, as a result of the hydrolysis test,
The strength retention rate in the body after 1 week was only 5 to 20%, and it was too dangerous to be used as a surgical suture that is expected to surely hold the sutured portion for at least 1 week. .

An object of the present invention is to provide a biodegradable polymer having an appropriate hydrolysis rate and being flexible when processed into a fiber or a film. A suitable hydrolysis rate is 30
It means that the strength reduction rate of the fiber or film after 1 week in water at neutral temperature of 5 to 50%.

[Means for Solving Problems] The present inventors have found that these problems can be solved by introducing a polypropylene glycol group having high hydrophilicity and flexibility into the polymer chain of polylactic acid. Has reached the present invention.

That is, the present invention has the following general formula (In the formula, m and m ′ are positive integers from 1 to 6805, including zero, which cannot both be zero at the same time, and the sum of them is from 3 to
6805 is a positive integer, n is a positive integer of 2 to 172) 70 to 98% by weight of the polylactic acid segment (A) represented by (A)
And a polypropylene glycol segment (B) in an amount of 2 to 30% by weight, and a method for producing the block copolymer.

In the block copolymer of the present invention, the polylactic acid segment (A) has a total of 70 in both m and m'in the above general formula.
Is 98% by weight, the amount of polypropylene glycol segment (B) is 2 to 30% by weight, and m and m'in the above general formula are positive integers from 1 to 6805 including zero, and the sum thereof. Is a positive integer from 3 to 6805, and m and m'are block copolymers in the form of ABA or AB which cannot be zero at the same time, or a mixture thereof.

The size of the polypropylene glycol segment (B) is usually 100 to 1 in terms of number average molecular weight.
It is about 0000, and preferably about 400 to 4000.
Therefore, n in the above general formula is a positive integer of 2 to 172.

If the amount of the polypropylene glycol segment (B) is less than 2% by weight in the copolymer, sufficient flexibility and hydrophilicity cannot be obtained, and if it exceeds 30% by weight, it becomes difficult to form a film or fiber. It is not preferable.

The block copolymer of the present invention can be obtained by polymerizing 1-lactide or dl-lactide or a mixture thereof with a cationic polymerization catalyst in the presence of polypropylene glycol.

As polypropylene glycol used here,
The above-mentioned polypropylene glycol segment (B) having a molecular weight can be used without any support, and the oxypropylene units may be connected in any manner, but preferably at least one terminal is a secondary OH group. What is present is suitable.

Also, the amount of polypropylene glycol used is 2 with respect to 100 parts by weight of the above lactide, depending on the composition of the target copolymer.
It is appropriately selected from the range of up to 100 parts by weight.

As the polymerization catalyst, a cationic polymerization catalyst is used,
Specific examples thereof include trialkylaluminum-based catalysts, preferably trimethylaluminum-water-based catalysts. The amount used is not particularly limited, but is appropriately determined depending on the monomer composition, the solvent used, the polymerization temperature and the like.

Polymerization can be achieved by heating and melting lactide and polypropylene glycol in an inert gas stream, mixing them, and then adding a catalyst, and usually reacting at 60 to 250 ° C., preferably 100 to 160 ° C. for several hours.

The film can be easily produced by, for example, dissolving the block copolymer obtained above in a solvent and forming a film by a casting method. Furthermore, fibers can be produced from the above block copolymer by a conventional method.

〔Example〕

Hereinafter, the present invention will be described with reference to examples. In the present invention, the physical properties of the polymer were analyzed by the following methods.

(1) Number average molecular weight Dissolve 1 g of polymer in 100 ml of tetrahydrofuran and use GPC
Was measured and the molecular weight was determined by a polystyrene standard.

(2) The 1 H-NMR polymer was dissolved in deuterated chloroform containing 1% by weight of tetramethylsilane and measured.

(3) Viscosity Chloroform was used as a solvent and a solution of 0.5 g / dl
It was measured at ± 0.1 ° C, and η _sp / c was calculated.

(4) Tensile Strength, Initial Young's Modulus, Elongation Using a ram type extruder, the polymer was spun while being heated to 200 ° C., and then measured with a tensile tester.

Examples 1 to 4 and Comparative Example 1 1-Lactide and polypropylene glycol having a number average molecular weight of 4000 (hereinafter referred to as PPG) were charged at the ratios shown in Table 1 and heated and melted at 130 ° C. for 30 minutes under an argon stream. Mixed. Then, a trimethylaluminum-water catalyst was added so as to be 1% by weight, and polymerization was carried out at 150 ° C. and 100 mmHg for 3 hours. After completion of the polymerization, acetic anhydride was added to acetylate the polymer terminal. The product was dissolved in chloroform, reprecipitated in ether, and then vacuum dried to obtain a polymer.

The physical properties of the obtained polymer were measured as described above, and the results shown in Table 1 were obtained. The ratio of polypropylene glycol segment to polylactic acid in the polymer is calculated by 1 H-NMR.

In addition, among the fibers used for measuring the above-mentioned various physical properties, Example 1
The samples of Comparative Example 1 and Comparative Example 1 were dipped in a phosphate buffer solution (pH 7.2, 30 ° C.), and the tensile strength reduction rate (hydrolyzability) of the thread after 1 week was measured to be 13.8% and 1.8%, respectively. And the one of Example 1 had better decomposability.

Examples 5 to 10 PPGs having a number average molecular weight of 2000 or 1000 are listed below.
A polymer was obtained in the same manner as in Example 1 except that the amount shown in 1 was used. Table 1 shows the physical properties of the obtained polymer.

Film Molding Test The polymers obtained in Examples 1 to 10 and Comparative Example 1 were dissolved in a chloroform solvent and cast on a stainless steel plate to form a film. It had better flexibility than that of Comparative Example 1.

〔The invention's effect〕

The block copolymer of the present invention has the same in-vivo hydrolyzability as that of polylactic acid, and also has sufficiently improved flexibility and hydrophilicity. From the block copolymer of the present invention, a film, fiber or the like having sufficient flexibility and strength for medical use can be easily molded, which is useful as a medical material. Furthermore, by incorporating a drug into the block copolymer of the present invention, it is possible to impart sustained release.

Further, according to the production method of the present invention, the degree of polymerization of the copolymer can be easily controlled, so that a copolymer having a degree of polymerization suitable for the purpose can be obtained.

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Claims (2)

[Claims] 1. The following general formula (In the formula, m and m ′ are positive integers from 1 to 6805, including zero, which cannot both be zero at the same time, and the sum of them is from 3 to
6805 is a positive integer, n is a positive integer of 2 to 172) 70 to 98% by weight of the polylactic acid segment (A) represented by (A)
And a polypropylene glycol segment (B) in an amount of 2 to 30% by weight. 2. The following general formula, characterized in that l-lactide and / or dl-lactide are polymerized in the presence of polypropylene glycol using a cationic polymerization catalyst. (In the formula, m and m ′ are positive integers from 1 to 6805, including zero, which cannot both be zero at the same time, and the sum of them is from 3 to
6805 is a positive integer, n is a positive integer of 2 to 172) 70 to 98% by weight of the polylactic acid segment (A) represented by (A)
And a polypropylene glycol segment (B) in an amount of 2 to 30% by weight, the method for producing a block copolymer.