CN108721683A - A kind of preparation method of biodegradable hemostasis mesh sheet - Google Patents

Abstract

The invention discloses a preparation method of a biodegradable hemostatic mesh, which is characterized in that a multi-block copolymer of polyethylene glycol-poly(L-lactide-glycolide-ε-caprolactone) is prepared first, and It is spun and woven into a mesh to obtain a biodegradable hemostatic mesh; the advantage is that the prepared polyethylene glycol-poly(L-lactide-glycolide-ε-caprolactone) multi-block copolymer Good flexibility, soft hand feeling after spinning into fibers, which overcomes the hard and rough defects of natural polymer hemostatic mesh; and the components of hemostatic mesh can be degraded by human enzymes, so it has good biocompatibility; In addition, it is formed into a mesh by melt spinning, and its preparation method is more green and environmentally friendly. It is safer to use because there is no solvent residue, and has less side effects on human tissues.

Description

A kind of preparation method of biodegradable hemostatic mesh

technical field

The invention relates to a preparation method of a medical hemostatic material, in particular to a preparation method of a biodegradable hemostatic mesh.

Background technique

Surgical minimally invasive surgery is very widespread in the world. Because of the small operable space, the cut tissue can only be hemostasis through packing, and it is not suitable for reoperation. Therefore, absorbable hemostatic materials have been widely used in minimally invasive surgery. Applications. The currently clinically used absorbable hemostatic material is mainly sodium carboxymethyl cellulose, which can be degraded by various enzymes in the body into small fragments or small molecules, and then absorbed or excreted by the body. However, the degradation products of sodium carboxymethyl cellulose are acidic substances, which can easily cause excessive acidity in local tissues and cause damage to tissues. At the same time, sodium carboxymethyl cellulose is made from cellulose through chemical reactions. The raw material cellulose may have problems such as different sources, unstable quality, and large differences in material properties. The performance is not good enough, so the liquid absorption rate and liquid absorption rate need to be further improved. Moreover, due to the large molecular weight of cellulose, it is difficult to make a homogeneous solution, and the chemical reaction to its modification cannot occur uniformly on the entire molecular chain, resulting in uneven performance of the sodium carboxymethyl cellulose material and affecting its hemostasis. effectiveness.

In addition to sodium carboxymethyl cellulose, there is another kind of more common hemostatic materials such as protein polymers such as collagen and gelatin. Because such materials are of animal origin, potential risks such as immune activation, microbial and viral infection are prone to occur during use, especially when a large amount of bleeding requires the use of more such products, the risk is even greater. On the other hand, due to differences in origin, breeding time, animal species, and post-processing methods of protein materials, the performance of protein materials has great differences and instability.

Contents of the invention

The technical problem to be solved by the present invention is to provide a method for preparing a biodegradable hemostatic mesh with soft texture, good safety, few side effects and adjustable degradation rate.

The technical scheme adopted by the present invention to solve the above-mentioned technical problems is: a preparation method of a biodegradable hemostatic mesh, comprising the following specific steps:

(1) Weigh polyethylene glycol with a weight-average molecular weight of 2000-10000 and put it into the reaction kettle, and add L-lactide, glycolide and ε-caprolactone at a molar ratio of 1:1:1 The mixture, control the mass ratio of polyethylene glycol to the mixture is 1:1-5, then add stannous octoate with a total mass ratio of 0.001-0.1% to polyethylene glycol and the mixture, and argon at 120-160°C Reaction in gas protection environment for 20 to 40 hours;

(2) Add a chain extender in an equimolar ratio to polyethylene glycol, stir and react for 20-40 hours in an argon-protected environment at a temperature of 100-150°C to obtain polyethylene glycol-poly(L-lactate) ester-glycolide-ε-caprolactone) multi-block copolymer;

(3) Granulate the multi-block copolymer obtained above, obtain fiber filaments with a fiber diameter of 0.1 to 0.5 mm by melt spinning, and then weave the fiber filaments into mesh sheets with various apertures as required by a weaving machine. A biodegradable hemostatic mesh is obtained.

Further, the chain extender is cyclohexyl 1,4-diisocyanate, 4,4'-methylene diisocyanate phenyl, 4,4'-diisocyanate dicyclohexylmethane or hexamethylene diisocyanate.

Compared with the prior art, the present invention has the advantages that the prepared polyethylene glycol-poly(L-lactide-glycolide-ε-caprolactone) multi-block copolymer has good flexibility and can be spun into fibers The back feels soft, overcoming the hard and rough defects of natural polymer hemostatic mesh; and the components of the hemostatic mesh can be degraded by human enzymes, so it has good biocompatibility; L-lactide, The copolymer obtained by polymerization of three monomers of glycolide and ε-caprolactone can flexibly adjust the proportion of components according to needs to adjust its degradation rate to better match the needs of tissue applications; in addition, it can be formed by melt spinning It is a mesh, its preparation method is more green and environmentally friendly, it is safer to use because there is no solvent residue, and it has less side effects on human tissues.

Detailed ways

Below in conjunction with embodiment the present invention is described in further detail.

Embodiment 1: A kind of preparation method of biodegradable hemostatic mesh, comprises the following specific steps:

(1) Weigh polyethylene glycol with a weight average molecular weight (Mw) of 2000 and put it into the reaction kettle, and add L-lactide, glycolide, ε-hexanol in a molar ratio of 1:1:1 A mixture of esters, control the mass ratio of polyethylene glycol and the mixture to 1:1, then add stannous octoate with a total mass ratio of polyethylene glycol and the mixture of 0.01%, and react at a temperature of 120°C in an argon-protected environment 40 hours;

(2) Add cyclohexyl 1,4-diisocyanate in an equimolar ratio to polyethylene glycol, and stir and react for 40 hours at a temperature of 100°C in an argon-protected environment to obtain polyethylene glycol-poly(L-propane multi-block copolymers of lactide-glycolide-ε-caprolactone);

(3) Granulate the multi-block copolymer obtained above, obtain fiber filaments with a fiber diameter of 0.3 mm by melt spinning, and then weave the fiber filaments into meshes with various apertures as required by a weaving machine to obtain biological Degrade the hemostatic mesh.

Embodiment 2: A preparation method of a biodegradable hemostatic mesh, comprising the following specific steps:

(1) Weigh polyethylene glycol with a weight-average molecular weight (Mw) of 10,000 and put it into the reactor, and add L-lactide, glycolide, ε-hexanol in a molar ratio of 1:1:1 A mixture of esters, control the mass ratio of polyethylene glycol and the mixture to 1:3, then add stannous octoate with a total mass ratio of polyethylene glycol and the mixture of 0.1%, and react in an argon-protected environment at a temperature of 160°C 20 hours;

(2) Add 4,4′-methylene diisocyanate phenyl in an equimolar ratio to polyethylene glycol, stir and react for 30 hours at a temperature of 120°C in an argon-protected environment to obtain polyethylene glycol - multi-block copolymers of poly(L-lactide-glycolide-ε-caprolactone);

(3) Granulate the multi-block copolymer obtained above, obtain fiber filaments with a fiber diameter of 0.1 mm by melt spinning, and then weave the fiber filaments into meshes with various apertures as required by a weaving machine to obtain biological Degrade the hemostatic mesh.

Embodiment three: a kind of preparation method of biodegradable hemostatic mesh, comprises the following specific steps:

(1) Weigh polyethylene glycol with a weight average molecular weight (Mw) of 6000 and put it into the reaction kettle, and add L-lactide, glycolide, ε-hexanol in a molar ratio of 1:1:1 A mixture of esters, control the mass ratio of polyethylene glycol to the mixture to 1:5, then add stannous octoate with a total mass ratio of 0.008% to polyethylene glycol and the mixture, and react in an argon-protected environment at a temperature of 140°C 35 hours;

(2) Add 4,4′-diisocyanate dicyclohexylmethane in an equimolar ratio to polyethylene glycol, and stir and react for 20 hours at a temperature of 150°C in an argon-protected environment to obtain polyethylene glycol-poly( Multi-block copolymers of L-lactide-glycolide-ε-caprolactone);

(3) Granulate the multi-block copolymer obtained above, obtain fiber filaments with a fiber diameter of 0.5 mm by melt spinning, and then weave the fiber filaments into meshes with various apertures as required by a weaving machine to obtain biological Degrade the hemostatic mesh.

Claims (2)

1. a kind of preparation method of biodegradable hemostasis mesh sheet, it is characterised in that including step in detail below：

（1）, weigh weight average molecular weight be 2000~10000 polyethylene glycol be put into reaction kettle, and be added molar ratio be 1：1：1 L- lactides, glycolide, 6-caprolactone mixture, the mass ratio for controlling polyethylene glycol and mixture is 1：1~5, then add Enter the stannous octoate for being 0.001~0.1% with the total mass ratio of polyethylene glycol and mixture, argon gas at a temperature of 120~160 DEG C It is reacted 20~40 hours in environmental protection；

（2）, be added with polyethylene glycol equimolar than chain extender, stirred in argon gas protection environment at a temperature of 100~150 DEG C Reaction 20~40 hours, obtains polyethylene glycol（L- lactide coglycolides -6-caprolactone）Segmented copolymer；

（3）, segmented copolymer obtained above is granulated, the fibre that fibre diameter is 0.1~0.5mm is obtained by melt spinning Silk is tieed up, then filament is weaved into the mesh sheet of multiple aperture on demand by braider, obtains biodegradable hemostasis mesh sheet.

2. a kind of preparation method of biodegradable hemostasis mesh sheet as described in claim 1, it is characterised in that：The chain extender For cyclohexyl 1,4- diisocyanate, 4,4 '-di-2-ethylhexylphosphine oxide phenyl isocyanates, 4,4 '-hexylmethanes or Hexamethylene diisocyanate.