CN103265719B - A kind of sthptic sponge and preparation method thereof - Google Patents

Abstract

The invention relates to a hemostatic sponge and an application thereof. The hemostatic sponge is finally prepared by re-denaturing the denatured starch in the prior art and subjecting it to heat stirring treatment. The hemostatic sponge has excellent water absorption effect, is safe and stable, and is a biocompatible hemostatic sponge that can be directly used on bloody wounds.

Description

A kind of hemostatic sponge and preparation method thereof

technical field

The invention relates to a hemostatic sponge and a preparation method thereof, in particular to a biocompatible hemostatic sponge which can be directly used on bloody wounds and a preparation method thereof.

Background technique

Bleeding is the most likely phenomenon in accidents and medical treatment. A large amount of bleeding will endanger human life. Therefore, it is necessary to stop bleeding in time for bleeding wounds.

With the development of medicine, there are many kinds of hemostatic materials. In terms of biocompatibility, commonly used biocompatible hemostatic materials include: absorbable gelatin sponge, collagen sponge and other gelatin hemostatic materials; oxidized cellulose, oxidized regeneration Cellulose hemostatic materials; chitosan/chitin, starch polysaccharides and other natural biopolysaccharide hemostatic materials, etc.

The content of the present invention relates to the hemostatic material of starch polysaccharides, and the relevant patent applications in this field are as follows:

CN200710141944.0 Absorbable hemostatic material with modified starch and its preparation method, CN200710199682.3 Biocompatible modified starch sponge, CN200810032631.6 Biocompatible modified starch material for hemostasis, anti-adhesion, healing and surgical sealing, CN200810033239. 3 Biocompatible pregelatinized modified starch and its preparation method, CN200810009706.9 Modified starch absorbable hemostatic material and its preparation method, CN200910045995.2 Biocompatible hemostatic and bone healing promotion material and its preparation method.

The above 6 patent applications have roughly the same content and are the same applicant or inventor. The above-mentioned patent discloses the use of partially modified starch in hemostasis, and proposes several specific modified starches, such as cationic starch, epichlorohydrin cross-linked starch, carboxymethyl starch, hydroxyethyl starch, pregelatinized denatured starch Starch, pregelatinized hydroxypropyl distarch phosphate, acrylic acid-carboxymethyl starch graft copolymer, etc., but their specific properties and detailed applications are not described.

The applicant conducted systematic research on the above-mentioned various modified starches, and found that the modified starch in the above-mentioned patent application had a low water absorption rate and unstable performance, and could not meet the clinical hemostasis requirements. After treating the starch to a certain extent, the applicant surprisingly found that its water absorption capacity and water absorption rate were greatly improved. The applicant has found through repeated experiments and researches that the modified starch in the prior art can be processed into a hemostatic sponge, which can greatly improve its water absorption and has an excellent application prospect. At the same time, the applicant has also screened out the optimal preparation raw material ratio and process parameters through experiments, and the preparation is more stable, safe and more beneficial to industrial production.

Contents of the invention

An object of the present invention is to provide a new hemostatic sponge, which has good water absorption, safety, and stable performance, and overcomes the shortcomings of low water absorption of modified starch and unstable preparations in the prior art.

Another object of the present invention is to provide the preparation method of described hemostatic sponge, and the object of the present invention is achieved by the following technical solutions:

A preparation method of hemostatic sponge, characterized in that: comprising the following steps:

1) Etherification, cross-linking, and esterification of the modified starch raw material to make new modified starch,

2) drying and freeze-drying at low temperature to obtain a hemostatic sponge.

Preferably, the modified starch raw material in step 1 is one of pregelatinized starch, acid-modified starch, dextrin, oxidized starch, esterified starch, etherified starch, cross-linked starch, grafted starch, and composite modified starch. combination of the above.

Preferably, a thermal stirring treatment step is added before, during or after step 1.

Preferably, the thermal stirring temperature is 85-90°C.

Preferably, the stirring speed during thermal stirring is 600-800r/min.

Preferably, the duration of stirring during thermal stirring is 150-200min.

Another technical scheme of the present invention designs the purposes of the hemostatic sponge prepared by the method of the present invention:

Used to prepare hemostatic material for bloody wounds of humans, mammals, birds and reptiles.

It is used to prepare hemostatic materials on the surface of the human body, tissues and organs in the body, and tissues or organs in the body cavity, or for surgical operations, first aid for trauma, laryngoscopes, endoscopes, and laparoscopes.

For the preparation of materials that promote tissue healing.

Preferably, the tissue includes subcutaneous soft tissue, muscle tissue, bone tissue, brain tissue, nerve tissue, liver, kidney, spleen.

It is used in the preparation of materials to prevent traumatic tissues or organs from adhering to other surrounding tissues or organs.

After the applicant has carried out a series of condition screening tests, it is found that the method of the present invention has the following characteristics:

Beneficial effects of the present invention:

1. The method of the present invention does not have any requirements on the type of modified starch. The modified starch commonly used in the prior art can be used in this method. The water absorption rate and water absorption rate of the prepared hemostatic sponge are much higher than those in the prior art. The modified starch sponge has obvious performance advantages. For example, compared with the control group, the water absorption rate is increased by more than 40% on average, and the water absorption rate is increased by more than 1 times, which has obvious performance advantages.

2. The heat stirring treatment step can be located before, during or after the denaturation process of the modified starch. As long as the heat stirring treatment step is used in the whole process of preparing the modified starch, the water absorption capacity and water absorption rate of the new modified starch obtained can be improved.

3. The present invention further breaks up the molecular structure of the starch by re-denaturing the existing modified starch and heat stirring treatment, greatly improving its water absorption performance, and screens out the optimal process parameters through a large number of experiments, so that The prepared hemostatic sponge is superior to similar products in the prior art in terms of water absorption performance, and has broad application prospects. The hemostatic sponge of the invention is convenient to prepare, has a more stable and safe preparation, and is more beneficial to industrialized production.

detailed description

The present invention will be further described in detail below in conjunction with specific embodiments, and the given examples are only for clarifying the present invention, not for limiting the scope of the present invention.

Example 1:

The hydroxypropyl distarch phosphate is etherified, cross-linked and esterified by chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into the mixer, and the Adjust the rotation speed of the stirrer at 85°C to 600r/min for 150min, filter with suction after cooling, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain a hemostatic sponge 1 .

Example 2:

Put the hydroxypropyl distarch phosphate slurry into the agitator, adjust the rotation speed of the agitator to 600r/min at 85°C for 150min, filter with suction after cooling, wash with alcohol, dry, and then pass epoxy Chemical reagents such as propane and phosphoric acid undergo etherification, cross-linking, and esterification to make new modified starch, freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours, and obtain the hemostatic sponge 2.

Example 3:

The hydroxyethyl starch is subjected to etherification, crosslinking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into a stirrer and heated at 85 ° C. Adjust the rotation speed of the stirrer to 600r/min, and the duration is 150min. After cooling, filter with suction, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 3.

Example 4:

Put the hydroxyethyl starch slurry into the agitator, adjust the rotation speed of the agitator to 600r/min at 85°C for 150min, filter with suction after cooling, wash with alcohol, dry, and pass through propylene oxide, phosphoric acid Etherified, cross-linked, and esterified chemical reagents were denatured multiple times to produce a new modified starch, and freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 4.

Example 5:

The carboxymethyl starch is subjected to etherification, cross-linking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into a stirrer and heated at 85°C. Adjust the rotation speed of the stirrer to 600r/min, and the duration is 150min. After cooling, filter with suction, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 5.

Embodiment 6:

Put the carboxymethyl starch slurry into the stirrer, adjust the speed of the stirrer to 600r/min at 85°C for 150min, filter with suction after cooling, wash with alcohol, dry, and pass through propylene oxide, phosphoric acid Etherification, cross-linking, and esterification of chemical reagents were carried out multiple denaturations to produce a new modified starch, which was freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 6.

Embodiment 7:

The cationic starch is subjected to etherification, crosslinking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then put the modified starch slurry into the mixer and adjust it at 85 °C. The rotation speed of the stirrer was 600r/min, and the duration was 150min. After cooling, it was suction-filtered, washed with alcohol, dried, and freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 7.

Embodiment 8:

Put the cationic starch slurry into the agitator, adjust the rotation speed of the agitator to 600r/min at 85°C, and last for 150min. After cooling, filter it with suction, wash with alcohol, dry it, and then pass it through chemical treatment such as propylene oxide and phosphoric acid. The reagent was denatured multiple times through etherification, crosslinking, and esterification to make a new modified starch, which was freeze-dried at -45° C. and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 8 .

Embodiment 9:

The hydroxypropyl distarch phosphate is etherified, cross-linked and esterified by chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into the mixer, and the Adjust the rotation speed of the stirrer at 90°C to 800r/min, and the duration is 200min. After cooling, filter with suction, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 9 .

Example 10:

Put the hydroxypropyl distarch phosphate slurry into the agitator, adjust the rotation speed of the agitator to 800r/min at 90°C, and the duration is 200min. After cooling, filter with suction, wash with alcohol, dry, and then pass epoxy Propane, phosphoric acid and other chemical reagents undergo etherification, cross-linking, and esterification for multiple denaturations to produce a new modified starch, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 10.

Example 11:

The hydroxyethyl starch is subjected to etherification, crosslinking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into a mixer and heated at 90 ° C. Adjust the rotation speed of the stirrer to 800r/min, and the duration is 200min. After cooling, filter with suction, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 11.

Example 12:

Put the hydroxyethyl starch slurry into the stirrer, adjust the speed of the stirrer to 800r/min at 90°C, and the duration is 200min. After cooling, filter with suction, wash with alcohol, dry, and then pass through propylene oxide, phosphoric acid Etherified, cross-linked, and esterified chemical reagents were denatured multiple times to produce a new modified starch, which was freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 12 .

Example 13:

The carboxymethyl starch is subjected to etherification, cross-linking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then put the modified starch slurry into a stirrer and heat it at 90°C. Adjust the rotation speed of the stirrer to 800r/min, and the duration is 200min. After cooling, filter with suction, wash with alcohol, dry, and freeze-dry at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 13.

Example 14:

Put the carboxymethyl starch slurry into the agitator, adjust the rotation speed of the agitator to 800r/min at 90°C for 200min, filter with suction after cooling, wash with alcohol, dry, and pass through propylene oxide, phosphoric acid Etherified, cross-linked, and esterified chemical reagents were denatured multiple times to produce a new modified starch, which was freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain a hemostatic sponge 14.

Example 15:

The cationic starch is modified by etherification, crosslinking and esterification with chemical reagents such as propylene oxide and phosphoric acid to make a new modified starch, and then the modified starch slurry is put into a stirrer and adjusted at 90°C. The rotation speed of the stirrer was 800r/min, and the duration was 200min. After cooling, it was suction-filtered, washed with alcohol, dried, and freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 15.

Example 16:

Put the cationic starch slurry into the agitator, adjust the rotation speed of the agitator to 800r/min at 90°C, and last for 200min. After cooling, filter it with suction, wash it with alcohol, dry it, and then pass it through propylene oxide, phosphoric acid and other chemicals. The reagent was denatured by etherification, cross-linking and esterification several times to make a new modified starch, which was freeze-dried at -45°C and a vacuum of 15 Pa for 15 hours to obtain the hemostatic sponge 16.

Embodiment 17 Control group experimental design

According to the methods of Examples 1, 3, 4, and 5 of the patent cn200710199682.3, the hemostatic sponges A, C, D, and E were respectively prepared as the control group.

Example 18 Detection of the water absorption ratio and water absorption rate of the hemostatic sponge

The water absorption rate of the sponge is determined by centrifugation, that is, about 0.025g of the sponge is placed in 2ml of water, balanced for 10 minutes, then placed in a centrifuge, and taken out after centrifugation at 500rpm for 10 minutes, and the amount of residual liquid is calculated by weighing. Each sample is tested for 6 Times to average.

The water absorption rate of the sponge was observed by the OCA40Micro video contact angle measuring instrument from Dataphysics, Germany.

Experimental results: The water absorption ratio and water absorption rate of the 16 kinds of hemostatic starches prepared by the methods of Examples 1-16 and the hemostatic sponges A, C, D, and E obtained by the control group of Example 17 are shown in the following table:

Table 1

Analysis of results:

The following conclusions can be drawn from the above experimental data:

1. The method of the present invention does not have any requirements on the type of modified starch. The modified starch commonly used in the prior art can be used in this method. The water absorption rate and water absorption rate of the prepared hemostatic sponge are much higher than those in the prior art. The modified starch sponge has obvious performance advantages. For example, compared with the control group, the water absorption rate is increased by more than 40% on average, and the water absorption rate is increased by more than 1 times, which has obvious performance advantages.

2. The heat stirring treatment step can be located before, during or after the denaturation process of the modified starch. As long as the heat stirring treatment step is used in the whole process of preparing the modified starch, the water absorption capacity and water absorption rate of the new modified starch obtained can be improved.

Example 4 Hemostatic Effect of Modified Starch Hemostatic Sponge on Hepatic Hemorrhage Model

experiment method:

Use a scalpel to cut the surface of the pig liver with a scalpel to cut the liver serosal layer with an area of 1.5cm×2.5cm, and the depth of the wound is 0.25cm to make a bleeding wound. Sponge A, C, D, E.

Hemostasis was performed on the above wounds respectively. Immediately after the bleeding, place the hemostatic sponge on the wound and apply pressure on the sponge with medical surgical gloves or hemostatic gauze to block the blood flow. After 1 to 2 minutes, gently loosen the glove or gauze to observe the hemostatic effect and whether the gloves and gauze Adhesion to sponge and blood clot, causing rebleeding when uncovered. After hemostasis, there is no need to remove or remove the modified starch sponge, but to properly infiltrate and rinse with physiological saline.

test results:

The hemostatic sponge 1-16 has a good hemostatic effect and is convenient to use. All hemostatic sponges absorb blood immediately after encountering blood, and form a sticky sponge-coagulant gel with blood, which can effectively control the bleeding of the liver wound within 1 minute, while the hemostatic sponges A, C, D, and E are at 1.5 Bleeding can be controlled within minutes. The hemostatic sponge 1-90 closely adheres to the wound tissue of the liver to promote blood coagulation, and the blood clot does not adhere to the pressed gauze dressing, which will not cause further bleeding.

Claims (7)

1. the preparation method of a sthptic sponge, it is characterised in that: comprise the following steps:

1) carry out modified starch raw material being etherified, cross-link, be esterified repeatedly degeneration after make new modified starch,

2) it is dried, lyophilizing under low temperature, obtains sthptic sponge,

Step 1) in modified starch raw material be pre-gelatinized starch, denaturated starch by acid, dextrin, Oxytarch, esterification form sediment One or more combination in powder, etherification starch, crosslinked starch, graft starch, composite modified starch；

In step 1) before, among or afterwards add thermal agitation process step；

Described thermal agitation temperature is 85-90 DEG C；

In described thermal agitation, speed of agitator is 600-800r/min；

In described thermal agitation, the stirring persistent period is 150-200min.

2. the sthptic sponge that method described in claim 1 prepares.

3. the purposes of the sthptic sponge of claim 2, its feature exists: be used for preparing people, birds, reptile have The hemostatic material of blood wound surface.

4. the purposes of the sthptic sponge of claim 2, its feature exists: be used for preparing body surface, in-vivo tissue device Official has blood wound surface or the hemostatic material under surgical operation, emergency care of trauma, laryngoscope, endoscope, chamber mirror.

5. the purposes of the sthptic sponge of claim 2, it is characterised in that: for preparing the material promoting organization healing.

6. the purposes of the sthptic sponge of claim 5, it is characterised in that: described tissue includes sub-dermal soft tissue, flesh Meat tissue, osseous tissue, cerebral tissue, nervous tissue.

7. the purposes of the sthptic sponge of claim 2, it is characterised in that: tissue or the device of wound is prevented for preparation In the material that official and its hetero-organization of surrounding or organ stick together.