CN112063008B

CN112063008B - Water-soluble sponge with density gradient and preparation method and application thereof

Info

Publication number: CN112063008B
Application number: CN202010981633.0A
Authority: CN
Inventors: 熊墨勇; 熊一男; 姜志国; 张均; 李丙军; 潘小帆; 万辉; 蒋国昌; 王爽
Original assignee: Beijing Beikeda Medical Equipment Co ltd; Huizhou North Chemical Industry University Research Base Co ltd; Youerlai Changzhou Medical Technology Co ltd
Current assignee: Beijing Beikeda Medical Equipment Co ltd; Huizhou North Chemical Industry University Research Base Co ltd; Youerlai Changzhou Medical Technology Co ltd
Priority date: 2020-09-17
Filing date: 2020-09-17
Publication date: 2022-07-01
Anticipated expiration: 2040-09-17
Also published as: CN112063008A

Abstract

The invention discloses a preparation method of a water-soluble sponge with density gradient and application thereof in the field of nasal cavity hemostasis. The preparation method of the water-soluble sponge with the density gradient comprises the following steps: (1) preparing a high polymer aqueous dispersion solution marked as a dispersion solution A; (2) thickening the aqueous polyurethane dispersion, denoted as dispersion B; (3) mixing the dispersion A, B, and pouring into a centrifuge tube for centrifugation; (4) rapidly freezing the centrifuge tube filled with the sample in the step (3); (5) and taking out the completely frozen sample, and freeze-drying to obtain the water-soluble sponge with density gradient. The sponge is especially suitable for nasal cavity operation, can be used as hemostatic material, and has application effects of hemostasis by compression, no adhesion, and ablation by water jet.

Description

Water-soluble sponge with density gradient and preparation method and application thereof

Technical Field

The invention relates to a preparation method and application of a water-soluble sponge with density gradient, belonging to the field of biomedical consumables.

Background

The foam material is widely applied in daily life and production, for example, the soft foam material is widely applied to the fields of electronics, automobiles, home furnishing, sports and leisure and the like due to the characteristics of buffering, sound absorption, vibration isolation, heat preservation and filtration, and the hard structure foam is widely applied to the fields of building, aerospace, rail transit, wind power generation and the like due to the characteristics of light weight, high strength and flame retardance. However, most of the foams in the above application fields are insoluble and degradable, which is not environment-friendly on one hand and does not meet the application requirements of specific fields well on the other hand.

In medical hemostatic material field, the foam material that can melt by oneself after the operation can make things convenient for the doctor to observe the wound healing condition or carry out the secondary to the wound and dose, can greatly limit alleviate patient's the passing through simultaneously, need not special treatment after the wound heals completely moreover, only need wash through water and just can get rid of hemostatic foam material, has eliminated patient's postoperative hemostatic material and has got rid of the sense of fear of in-process.

Polyvinyl alcohol is often used for hydrophilic and superabsorbent foams because of its water solubility. Foams prepared based on polyvinyl alcohol disclosed in chinese patents with patent publication numbers CN 1289629A, CN 1095075A, CN 1557872A and CN 1095387 a both involve the addition of aldehyde and acid, the production process is not environment-friendly, and the product is not easy to be used as a medical hemostatic material. Chinese patent publication No. CN 102827442A discloses a preparation method of a polyvinyl alcohol-polyurethane super absorbent sponge, which obtains the super absorbent sponge by blending and foaming a polyvinyl alcohol aqueous solution and polyurethane, and relates to chemical reaction and the use of an organic tin catalyst, the process is complex, and certain risks exist when the product is applied to the field of medical hemostasis. Chinese patent publication No. CN 108587016 a discloses a polyvinyl alcohol water-soluble foam plastic and a preparation method thereof, which is to extrude and granulate by a twin-screw extruder to obtain an expandable master batch, and then to prepare a water-soluble foam by a microwave foaming process, wherein the foam has a closed-cell structure and a complex preparation process, and although the product has water solubility, the foam has a high density and is not easy to be used as a medical hemostatic material.

Disclosure of Invention

In order to overcome the defects of the application of the prior art in the field of medical hemostasis, the invention provides a preparation method of a water-soluble sponge, which is simple in production process and does not need to add a catalyst, aldehyde and acid. The sponge prepared by the method is suitable for medical hemostasis, especially nasal cavity hemostasis.

The invention solves the technical problems and adopts the following technical scheme:

the invention provides a preparation method of a water-soluble sponge with a density gradient, which comprises the following steps:

(1) preparing a high polymer aqueous dispersion marked as A;

(2) thickening the aqueous polyurethane dispersion, denoted as B;

(3) a, B, mixing, pouring into a mould, and centrifuging;

(4) rapidly freezing the mould filled with the sample in the step (3);

(5) and taking out the completely frozen sponge blank, and freeze-drying to obtain the water-soluble sponge with density gradient.

Specifically, in the step (1), one or more than two water-soluble polymers are swelled in deionized water for 12-24 h, and then stirred and dissolved to obtain uniform and stable dispersion liquid A, wherein the vacuum degree is controlled to be-0.09 to-0.095 MPa in order to avoid generation of bubbles. To increase the rate of dissolution, the temperature may be increased.

The weight percentage of the high polymer aqueous dispersion in the step (1) is 2-20%, preferably 5-15%. The polymer is one or more of polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, gelatin, carboxymethyl cellulose, hydroxyethyl methyl cellulose and hydroxypropyl ethyl cellulose.

The aqueous polymer dispersion in the step (1) contains methanol or ethanol or a mixture of methanol and ethanol, the adding sequence of the aqueous polymer dispersion is prior to the adding of the water-soluble polymer, and the mass fraction of the aqueous polymer dispersion in deionized water is 0-10%, preferably 0.5-5%.

In the step (2), the thickening of the waterborne polyurethane is carried out at room temperature, and the vacuum degree is controlled to be-0.09 to-0.095 MPa in order to avoid the generation of bubbles.

Wherein the solid content of the aqueous polyurethane dispersion liquid in the step (2) is 15-50%, preferably 25-40%.

Wherein the elongation at break of the film after the waterborne polyurethane is cured in the step (2) is more than or equal to 700 percent, and the 100 percent modulus is 1-2 MPa.

The aqueous polyurethane dispersion liquid in the step (2) contains an aqueous polyurethane associative thickener, and the mass fraction of the aqueous polyurethane associative thickener is 1-5%, preferably 2-4%.

The mixing ratio of the A, B dispersion liquid in the step (3) is 1-10: 1, preferably 2-6: 1, and the vacuum degree in the mixing process is controlled to be-0.09-0.095 MPa. And after uniform mixing, pouring the mixed solution into a mold, and centrifuging for 30-180 s under the condition of 5000-15000 r/min.

The freezing temperature in the step (4) of the present invention is-25 ℃ or lower.

In the step (5), the blank body which is completely frozen in the mold is taken out, and then is frozen and dried for 24-36 hours at-80 ℃ to obtain the water-soluble sponge with density gradient.

In the present invention, the water-soluble sponge is shaped by a mold. In one embodiment, the water-soluble sponge in the form of a strip or column is prepared by providing a mold having a tubular cavity structure. In another embodiment, the sheet-form, water-soluble sponge is prepared by providing a mold having a sheet-form cavity structure.

In the technical scheme of preparing the nasal cavity hemostatic cotton, one technical scheme is to use a centrifugal tube as a mold. The inner diameter of the centrifugal tube is 0.5-2cm, and the height of the centrifugal tube is 2-10 cm.

In a preferred embodiment of the present invention, when using a mold having a tubular cavity structure, the axis of rotation of the centrifuge is collinear with the central axis of the cavity of the tubular cavity. The centrifuge rotates to drive the mould to rotate around the central axis thereof, so that the components of the mixed liquid in the mould are distributed in a gradient way due to the density difference.

The water-soluble sponge with the density gradient prepared by the method is characterized in that the average density of the sponge is 40-80 g/cm³The average pore diameter of the sponge core part is 1-3 mm, and the average pore diameter of the sponge skin is 0.1-0.3 mm.

The water-soluble sponge with the density gradient is suitable for medical hemostasis, and is particularly suitable for hemostasis in nasal cavity operation.

The inventor of the invention finds that the water-soluble sponge with the density gradient swells to form a compact water-containing layer on the surface of the sponge after absorbing water in a limited space, such as a nasal cavity. In the aqueous layer, water molecules are bonded to the water-soluble polymer to form hydrogen bonds between water and the water-absorbing groups of the polymer. Further, the above hydrogen bonds fix water molecules, resulting in water losing fluidity. In the confined space, the water-soluble polymer swells after absorbing water, but due to the confined space, the interior of the polymer is extruded, and a water-containing layer with a compact structure is formed on the surface, so that the further entry of water is hindered.

Compared with the surface, the pore diameter of the material core is larger, so that the material core no longer conforms to the condition of a limited space after absorbing water, and free water molecules and a space for flowing of the free water molecules still exist inside the material core. The free water molecules enter the material, so that the polymer is dissolved and the crystal is damaged under certain conditions, and further the structure of the material is damaged.

The innovation of the invention is that based on water-soluble polymers, the pore size, porosity and density of the foam material are adjusted by a dissolving, centrifuging and freeze drying method, so that a compact water-containing layer is formed on the surface of the material after water absorption, and liquid is prevented from further immersing into the material. The invention is also innovative in that the core of the material provides a larger pore size and a larger porosity. By injecting water into the core of the material, the material absorbs water and structural collapse occurs, further dissolving the material to facilitate removal of the material from the confined space. In the application scene of the invention, the innovation points enable the water-soluble sponge with the density gradient to realize the application effects of expansion hemostasis, no adhesion and easy taking out in the nasal cavity hemostasis operation, thereby greatly relieving the pain and fear of patients.

Detailed Description

For a better understanding of the present invention, the following examples are set forth to illustrate, but are not to be construed as the limit of the present invention.

The indentation performance is carried out according to a GB/T10807-2006 test method B method; density was measured according to test method GB 6343-1995; the pore size was measured by optical microscopy, taking the average of 50 pore size measurements; after the sponge with water solubility is soaked in deionized water for 12 hours, the observation volume is obviously reduced, the sponge cannot be taken out by tweezers, the volume does not change obviously, and the sponge cannot be taken out by tweezers.

The raw materials used were derived as follows:

waterborne polyurethane AH-1618 with a solid content of 50% (Anhui Dahuatai new materials Co., Ltd., China).

Waterborne polyurethane Leasys 1258 with a solid content of 38% (Wanhua chemical group, Inc., China).

Associative thickener Vesmody U505 (wawa chemical group, ltd., china).

Associative thickener AH-1509 (New Material, Inc., DAHUATAI, Anhui, China).

Polyvinyl alcohol 1788 (shanxi three-dimensional group ltd, china).

Hydroxyethyl methylcellulose (sieravia biotechnology limited, china).

Carboxymethyl cellulose (Fuchu Kewei chemical Co., Ltd., China).

Polyvinylpyrrolidone K90 (basf, germany).

Example 1

(1) 200ml of a dispersion containing 7% polyvinyl alcohol 1788 and 3% hydroxyethyl methylcellulose were prepared. Firstly, adding polyvinyl alcohol 1788 and hydroxyethyl methyl cellulose into deionized water containing 2 percent of ethanol for swelling for 24 hours, and then stirring for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(2) Adding 2% of thickening agent AH-1509 into 50ml of waterborne polyurethane AH-1618, and stirring for 2h under the vacuum condition of room temperature and-0.095 MPa to obtain uniform dispersion B.

(3) Mixing 200ml of A and 50ml of B, stirring uniformly at room temperature under the vacuum condition of-0.095 MPa, then pouring into a centrifuge tube, and centrifuging for 60s under the condition of 10000 r/min.

(4) Freezing the centrifuge tube filled with the sample in the step (3) at-25 ℃ for 12 h.

(5) Taking out the completely frozen sample, and freeze-drying at-80 ℃ for 24h to obtain the water-soluble sponge with density gradient.

Example 2

(1) 200ml of an aqueous dispersion containing 10% polyvinyl alcohol 1788 were prepared. Firstly, adding polyvinyl alcohol 1788 into deionized water containing 2 percent of ethanol for swelling for 24 hours, and then stirring for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(3) Mixing 200ml of dispersion A and 50ml of dispersion B, stirring uniformly at room temperature under-0.095 MPa vacuum, pouring into a centrifuge tube, and centrifuging for 60s at 12000 r/min.

Example 3

(1) 250ml of an aqueous dispersion containing 10% polyvinyl alcohol 1788 was prepared. Firstly, adding polyvinyl alcohol 1788 into deionized water containing 2 percent of ethanol for swelling for 24 hours, and then stirring for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(3) Mixing 250ml of dispersion A and 50ml of dispersion B, stirring uniformly at room temperature under-0.095 MPa vacuum, pouring into a centrifuge tube, and centrifuging at 6000r/min for 60 s.

Example 4

(1) 250ml of an aqueous dispersion containing 7% polyvinylpyrrolidone K90 and 3% carboxymethylcellulose were prepared. Firstly, polyvinylpyrrolidone K90 and carboxymethyl cellulose are added into deionized water to swell for 24 hours, and then the mixture is stirred for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(2) Adding 2% of thickening agent Vesmody U505 into 50ml of waterborne polyurethane Leasys 1258, and stirring for 2h under the vacuum condition of room temperature and-0.095 MPa to obtain uniform dispersion liquid B.

(3) Mixing 250ml of dispersion A and 50ml of dispersion B, stirring uniformly at room temperature under-0.095 MPa vacuum, pouring into a centrifuge tube, and centrifuging at 8000r/min for 100 s.

Example 5

(1) 250ml of an aqueous dispersion containing 10% polyvinylpyrrolidone were prepared. Firstly, polyvinylpyrrolidone K90 is added into deionized water to swell for 24 hours, and then the mixture is stirred for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(3) Mixing 250ml of the dispersion A and 50ml of the dispersion B, stirring uniformly under vacuum at room temperature and-0.095 MPa, pouring into a centrifuge tube, and centrifuging at 15000r/min for 100 s.

Comparative example 1

(1) 200ml of an aqueous dispersion containing 10% polyvinyl alcohol 1788 were prepared. Firstly, adding polyvinyl alcohol 1788 into deionized water to swell for 24 hours, and then stirring for 6 hours under the vacuum condition of 60 ℃ and-0.095 MPa to obtain uniform dispersion A.

(3) Mixing 200ml of dispersion A and 50ml of dispersion B, stirring uniformly under vacuum condition of-0.095 MPa at room temperature, and freezing at-25 deg.C for 12 h.

(4) The completely frozen sample is freeze-dried for 24h at-80 ℃ to obtain the composite sponge.

Comparative example 2

Freezing 100ml of waterborne polyurethane AH-1618 at-25 ℃ for 12 h; the thoroughly frozen sample was freeze-dried at-80 ℃ for 24h to give a polyurethane sponge.

Comparative example 3

According to the method of example 1, the speed of centrifugation in step (3) was set to 3000r/min, and the remaining conditions were unchanged, thereby obtaining a polyurethane sponge.

Comparative example 4

Polyurethane sponge was obtained by following the procedure of example 1, setting the speed of centrifugation in step (3) to 20000r/min, and keeping the conditions unchanged.

Table 1 examples 1-5, comparative examples 1-2 foam performance parameter controls:

the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions and simplifications are intended to be included in the scope of the present invention.

Claims

1. The preparation method of the water-soluble sponge with the density gradient is characterized by comprising the following steps of: (1) preparing a high polymer aqueous dispersion solution marked as a dispersion solution A; (2) the aqueous polyurethane dispersion is marked as dispersion B; (3) mixing the dispersion liquid A, B to obtain a mixed liquid C, pouring the mixed liquid C into a mold, and centrifuging the mold filled with the mixed liquid C; (4) rapidly freezing the centrifuged mold; (5) taking out the sponge blank from the frozen mould, and freeze-drying the blank to obtain the water-soluble sponge with density gradient; wherein the polymer in the step (1) is one or a combination of more of polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, gelatin, carboxymethyl cellulose, hydroxyethyl methyl cellulose and hydroxypropyl ethyl cellulose; wherein the speed of centrifugation in the step (3) is 5000-15000 r/min; wherein the quick freezing in the step (4) is to freeze the mould to a temperature not higher than-25 ℃ within 5 min;

wherein in the step (1), the mass fraction of the high polymer aqueous dispersion is 2-20%; in the step (2), the solid content of the aqueous polyurethane dispersion liquid is 15-50%; in the step (3), the mixing ratio of the dispersion liquid A, B is 1-10: 1; in the step (4), the centrifugation time is 30-180 s.

2. The method for preparing a water-soluble sponge having a density gradient as claimed in claim 1, wherein in the step (1), the weight fraction of the aqueous polymer dispersion is 5% to 15%.

3. The method for preparing a water-soluble sponge with a density gradient according to claim 1, wherein in the step (1), the polymer aqueous dispersion contains methanol or ethanol, and the mass fraction of methanol or ethanol in the polymer aqueous dispersion is 0.5-5%.

4. The method for preparing the water-soluble sponge with the density gradient according to claim 1, wherein in the step (2), the solid content of the aqueous polyurethane dispersion is 25-40%.

5. The method for preparing the water-soluble sponge with the density gradient as claimed in claim 1, wherein in the step (2), the aqueous polyurethane dispersion liquid contains an aqueous polyurethane associative thickener, and the mass fraction of the associative thickener in the aqueous polyurethane dispersion liquid is 1-5%.

6. The method for preparing the water-soluble sponge with the density gradient according to claim 5, wherein in the step (2), the associative thickener accounts for 2-4% of the mass of the aqueous polyurethane dispersion liquid.

7. The method for preparing the water-soluble sponge with the density gradient as claimed in claim 1, wherein in the step (3), the A, B dispersion liquid is mixed in a ratio of 2-6: 1.

8. The method for preparing a water-soluble sponge having a density gradient as claimed in claim 1, wherein the mold in step (3) is a mold having a tubular cavity structure.

9. The water-soluble sponge having a density gradient, which is prepared by the method for preparing a water-soluble sponge having a density gradient according to any one of claims 1 to 8.

10. The water-soluble sponge having a density gradient according to claim 9, wherein the average density of the water-soluble sponge is 40 to 80g/cm3, the average pore size of the sponge core is 1 to 3mm, and the average pore size of the sponge skin is 0.1 to 0.3 mm.

11. Use of a water-soluble sponge with a density gradient according to claim 9 in a medical consumable of the hemostatic type.