TW202220707A - Hemostatic material for use of making hemostatic composition - Google Patents

Abstract

The present invention is related to a hemostatic material, which is applied for making hemostatic composition and delivered to a wound so as to achieve hemostasis. The hemostatic material comprises a hemostatic complex and an excipient complex; the hemostatic complex is a bio-absorbable water absorbent material comprising natural polysaccharides; the excipient complex comprises a swelling agent, a thickening agent, an electrolyte and a contrast agent. Based on the total weight of the hemostatic material, the hemostatic material comprises 30-99.9%(w/w) the hemostatic complex, the excipient complex comprises 0.1-30% (w/w) the swelling agent, 0.1-15% (w/w) the thickening agent, 0.1-10% (w/w) the electrolyte and 0.1-20% (w/w) the contrast agent. A use of the hemostatic material for making hemostatic composition is to administrate an effective dosage of the hemostatic material to a wound of a subject in need.

Description

Hemostatic material for preparing hemostatic composition

The present invention relates to a hemostatic material and a method for hemostasis, in particular to a hemostatic material containing natural polysaccharides and the use of the hemostatic material for preparing a hemostatic composition.

Gastrointestinal bleeding is a fairly common and potentially fatal disease in clinical practice, and it is extremely difficult for gastroenterologists to encounter bleeding from gastrointestinal cancer when performing endoscopy. When bleeding occurs, medical treatments such as drugs (such as hemostatic agents), electrocautery, or vascular clips are currently used clinically to control bleeding. With the above methods, about 85% of patients can successfully achieve hemostasis. However, in the other 15% of cases, complete hemostasis cannot be achieved with the existing methods, or the patients must endure hemostasis before bleeding (re- bleeding) risk.

According to the known hemostatic materials and hemostatic methods, such as "ADHESIVE MEDICAL PRODUCTS AND METHODS FOR TREATING GASTROINTESTINAL LESIONS" disclosed in US Patent Application No. US20190343980A1, which is characterized by the use of multi-layer coating layers to achieve hemostasis of active bleeding The purpose is to use a hemostatic layer containing a hemostatic agent to directly act on the active bleeding lesions in the form of powder, liquid or colloid, and then use a protective layer containing an adhesive to directly act on the aforesaid in the form of powder, liquid or colloid. The hemostatic layer and the surrounding tissue of the lesion are used to achieve the purpose of hemostasis.

According to the conventional hemostatic materials and hemostatic methods, such as Hemospray ^® produced by Cook Medical, it is a hemostatic powder mainly composed of minerals, which can absorb the liquid of the bleeding lesions and form a viscous film to Covering the bleeding lesions, the purpose is to concentrate coagulation factors and platelets to promote the activation of the coagulation mechanism; however, after achieving hemostasis in the gastrointestinal tract, it is often quickly discharged from the gastrointestinal tract, so in the case of massive bleeding, although it can effectively achieve hemostasis, However, in inactive bleeding lesions with high risk of rebleeding, such as exposed blood vessels, the effect of hemostasis and protection of bleeding lesions is compromised.

According to the known hemostatic materials and hemostatic methods, such as the product HaemoCer™ PLUS Absorbable Polysaccharide Haemostat (APH) provided by BioCer in Germany, it is an absorbable plant polysaccharide hemostatic agent, which will rapidly increase when it comes into contact with blood. It dehydrates the blood and accelerates the concentration of platelets, red blood cells and coagulation factors, and produces an elastic colloidal matrix to adhere to the bleeding site to prevent bleeding; although HaemoCer™ PLUS Absorbable Polysaccharide Haemostat (APH) composed of pure plant polysaccharides ) can be decomposed by amylase several days after administration and absorbed by the human body, but there may still be residual problems due to the amount of use.

Hemostatic powders currently on the market for endoscopy, including TC-325, Endoclot ^® and Ankaferd Blood, have different chemical compositions with individual properties and mechanisms of action. In general, when they come into contact with liquids, they instantly change from powder to gel to form a stable barrier to insulate bleeding and enhance clot formation for hemostasis. Among them, TC-325 has been tested by several large medical centers and showed that the initial hemostasis rate (Initial hemostasis rate) in the first week after surgery was 96.5%, but the rebleeding rate was 26.7%, while the initial hemostasis rate of Ankaferd hemostatic agent and Endoclot was 83.3% and 64%, respectively. Although these products have excellent initial hemostasis rate clinically, they still have their shortcomings, mainly due to the insufficient adhesion of the gel formed by them, making it difficult to maintain hemostasis, and some of the product ingredients are non-absorbable mineral ingredients, which are composed of The short excretion time from the body prevents its hemostatic effect from being maintained for a long time, thereby increasing the risk of rebleeding. In addition, the powder often blocks the catheter due to premature gel formation, and the random dispersion of the powder from the end of the catheter further causes blurring of the endoscopic field of view, making it difficult for the operator to handle the lesion.

In order to solve the problems of effective hemostasis, maintaining hemostasis for a long time, reducing rebleeding and residual hemostatic material, one object of the present invention is to provide a hemostatic material for preparing a hemostatic composition and delivering it to a wound, so as to achieve the effect of rapid hemostasis; Wherein, the hemostatic material includes: a hemostatic composition, which is a bioabsorbable water-absorbing material, and is composed of natural polysaccharides; and an excipient composition, which includes a swelling agent, a thickening agent, an electrolyte and a The developer, the swelling agent is a synthetic polymer substance, the thickening agent is an animal-derived protein, and based on the total weight of the hemostatic material, the hemostatic material contains 30-99.9% (w/w) hemostatic composition, the excipient is The shape composition contains 0.1~30% (w/w) swelling agent, 0.1~15% (w/w) thickener, 0.1~10% (w/w) electrolyte and 0.1~20% (w/w) w) developer.

In some embodiments, the delivery treatment is delivered to the wound or around the wound by spraying, spraying or coating through a catheter or a solid carrier, the catheter being an endoscopic catheter, a laparoscopic catheter or a thoracoscopic catheter; The solid carrier is bandage, gauze or hemostatic cotton; the wound is caused by ulcer, mucosal damage, vascular exposure, fistula or surgery, the surgery is esophagectomy, vascular anastomosis, endoscopic submucosal dissection or endoscopic mucosal resection cause.

In some preferred embodiments, the hemostatic material achieves hemostasis within 3-10 seconds after delivery to the wound.

In some preferred embodiments, after the hemostatic material is delivered to the wound, hemostasis can be maintained for 5 minutes to 72 hours under the bleeding pressure of 150-210 mmHg.

Another object of the present invention is to provide the use of a hemostatic material for preparing a hemostatic composition, which is to deliver the composition with an effective dose of the hemostatic material to the wound of a desired individual, so as to achieve the effect of hemostasis; wherein, the The hemostatic material includes: a hemostatic composition, which is a bioabsorbable water-absorbing material, and is composed of natural source polysaccharides; and an excipient composition, which includes a swelling agent, a thickening agent, an electrolyte and a developing agent, The swelling agent is an artificial synthetic polymer substance, the thickening agent is animal-derived protein, and based on the total weight of the hemostatic material, the hemostatic material comprises 30-99.9% (w/w) hemostatic composition, the excipient composition Contains 0.1~30% (w/w) swelling agent, 0.1~15% (w/w) thickener, 0.1~10% (w/w) electrolyte and 0.1~20% (w/w) developer.

In some preferred embodiments, the effective dose is 1.0-6.0 g/mm ² .

In some embodiments, the delivery treatment is delivered to the wound or around the wound by spraying, spraying or coating through a catheter or a solid carrier; preferably, the catheter is an endoscopic catheter, a laparoscopic catheter or Thoracoscopic catheter; preferably, the solid carrier is bandage, gauze or hemostatic cotton; the wound is caused by ulcer, mucosal damage, vascular exposure, fistula or surgery, and the surgery is esophagectomy, vascular anastomosis, endoscopic submucosal dissection surgery or endoscopic mucosal resection.

In some embodiments, the hemostatic material achieves hemostasis within 3-10 seconds after delivery to the wound.

In some embodiments, the hemostatic material can maintain hemostasis for 5 minutes to 72 hours at a bleeding pressure of 150 to 210 mmHg after delivery to the wound.

The hemostatic material for preparing the hemostatic composition provided by the present invention has better water absorption, fast gel formation and good adhesion, and can be used in the treatment of gastrointestinal bleeding, such as ulcers, mucosal damage, diffuse bleeding, and endoscopic submucosal dissection. Bleeding caused by surgery or endoscopic mucosal resection can be directly applied to the bleeding site through an endoscopic catheter, which quickly forms gel and achieves the effect of hemostasis. Moreover, the hemostatic material is made of bioabsorbable materials, which can be applied to the gastrointestinal tract. Absorbed by the individual, there is no residual risk; the added contrast agent can assist the user to directly track the attachment position of the hemostatic powder with X-ray, so that the individual does not have to endure the discomfort caused by endoscopy or surgery.

One embodiment of the present invention provides a hemostatic material for preparing a hemostatic composition for delivery to a wound to achieve rapid hemostasis; wherein the hemostatic material comprises a hemostatic composition and an excipient composition.

The hemostatic composition is a bioabsorbable water-absorbing material, used to absorb the water contained in the blood exuded from the wound, and further form a gel to cover the wound. The hemostatic composition is composed of natural polysaccharides, including guar Guar gum, Alginate, Gellan gum, Tragacanth, Xanthan gum, Chitosan, Sodium starch glycolate starch glycolate), sucrose (Sucrose), sorbitol (Sorbitol), mannitol (Mannitol), starch (Starch), dextran (Dextran) or a combination thereof.

The excipient composition includes a swelling agent, a thickening agent, an electrolyte and a developing agent. The swelling agent is a bioabsorbable synthetic polymer substance, which increases the swelling degree of the hemostatic composition to avoid contact with When the blood exuded from the wound, it quickly coagulates into a block, which causes the uneven distribution of the hemostatic composition in the wound and reduces the stability of the gel-forming structure; wherein, the swelling agent includes calcium polycarbophil (Calcium polycarbophil), polyethylene glycol Alcohol (Polyethylene glycol), polyethylene oxide (Polyethylene oxide), Poloxamers (Poloxamers) or their combination; the thickener is animal-derived protein, used to improve the density of the hemostatic composition when it forms a gel , to promote blood coagulation to enhance the initiation of coagulation mechanism, to achieve rapid hemostasis, the thickener contains gelatin (Gelatin), collagen (Collagen) or a combination thereof; the electrolyte contains calcium phosphate (Calcium phosphate), calcium chloride (Calcium chloride) ), calcium lactate (Calcium lactate), zinc acetate (Zinc acetate), zinc oxide (Zinc oxide) or a combination thereof; the developer is an X-ray developer.

The components of the hemostatic material, based on the total weight of the hemostatic material, comprise 30-99.9% (w/w) hemostatic composition, and the excipient composition comprises 0.1-30% (w/w) swelling agent, 0.1~15% (w/w) thickener, 0.1~10% (w/w) electrolyte and 0.1~20% (w/w) developer.

In some preferred embodiments, the hemostatic material comprises 68-88% (w/w) hemostatic composition, the excipient composition comprises 3-16% (w/w) swelling agent, 3-12% (w/w) w/w) thickener, 1~6% (w/w) electrolyte and 3~12% (w/w) developer.

Another embodiment of the present invention provides the use of a hemostatic material for preparing a hemostatic composition, which is to deliver the composition with an effective dose of the hemostatic material to the wound of a desired individual to achieve the effect of hemostasis; wherein, The hemostatic material comprises: a hemostatic composition, which is a bioabsorbable water-absorbing material, and is composed of natural polysaccharides; and an excipient composition, which includes a swelling agent, a thickening agent, an electrolyte and a developing agent , the swelling agent is a synthetic polymer substance, the thickening agent is an animal-derived protein, and based on the total weight of the hemostatic material, the hemostatic material contains 30-99.9% (w/w) of the hemostatic composition, the excipient composition The compound contains 0.1~30% (w/w) swelling agent, 0.1~15% (w/w) thickener, 0.1~10% (w/w) electrolyte and 0.1~20% (w/w) The developer; preferably, the developer is an X-ray developer; the hemostatic composition comprises guar gum, alginate, gellan gum, tragacanth ), Xanthan gum, Chitosan, Sodium starch glycolate, Sucrose, Sorbitol, Mannitol, Starch , Dextran or a combination; the swelling agent includes Calcium polycarbophil, Polyethylene glycol, Polyethylene oxide, Poloxamers or a combination thereof; the thickening agent comprises gelatin, collagen (Collagen) or a combination thereof; the electrolyte comprises calcium phosphate (Calcium phosphate), calcium chloride (Calcium chloride), calcium lactate (Calcium lactate), zinc acetate (Zinc acetate), zinc oxide (Zinc oxide) or a combination thereof.

For the above purposes, it is used in wounds of humans, mammals, birds, and reptiles to achieve hemostasis; Hemostasis of organs in body cavities, such as for surgery, external trauma, hemostasis under endoscopy, including rhinoscopy, laryngoscopy, gastroscope, colonoscopy, laparoscopy and thoracoscopy; more particularly, for use in Human body surface, tissue, organ or body cavity tissue or organ, including skin, subcutaneous soft tissue, muscle tissue, bone, brain, nerve tissue, liver, kidney, spleen, stomach, intestine and other organs and mucosal tissue; the delivery process It is delivered to the wound or around the wound by means of ejection, spray or spread through a catheter or a solid carrier; specifically, the catheter is an endoscopic catheter, a laparoscopic catheter or Thoracoscopic catheter; specifically, the solid carrier is a bandage, gauze, or hemostatic cotton; more specifically, the wound is caused by ulceration, mucosal damage, vascular exposure, fistula, or surgery, such as esophagectomy, vascular anastomosis, endoscopy Submucosal dissection or endoscopic mucosal resection.

In some preferred embodiments, the hemostatic material achieves hemostasis within 3, 4, 5, 6, 7, 8, 9 or 10 seconds after delivery to the wound.

In other embodiments, after the hemostatic material is delivered to the wound, hemostasis can be maintained for 5 minutes to 72 hours under the bleeding pressure of 150-210 mmHg.

Several embodiments and experimental examples are listed below to further illustrate the technical characteristics of the present invention, the application of technical means and the expected effect:

Example 1

A hemostatic material consisting of 20% (w/w) hemostatic composition, 30% (w/w) swelling agent, 20% (w/w) thickening agent, 10% (w/w) electrolyte and 20% (w/w) prepared by mixing the developer.

Example 2

A hemostatic material consisting of 30% (w/w) hemostatic composition, 30% (w/w) swelling agent, 15% (w/w) thickening agent, 10% (w/w) electrolyte and 15% (w/w) prepared by mixing the developer.

Example 3

A hemostatic material consisting of 60% (w/w) hemostatic composition, 15% (w/w) swelling agent, 10% (w/w) thickening agent, 5% (w/w) electrolyte and 10% (w/w) prepared by mixing the developer.

Example 4

A hemostatic material prepared by mixing 90% (w/w) hemostatic composition, 4% (w/w) swelling agent, 3% (w/w) thickening agent, 3% (w/w) electrolyte made.

Example 5

A hemostatic material is prepared from 100% (w/w) hemostatic composition.

Example 6

A hemostatic material consisting of 83% (w/w) hemostatic composition, 5% (w/w) swelling agent, 5% (w/w) thickening agent, 2% (w/w) electrolyte and 5% (w/w) prepared by mixing the developer.

Experimental example 1

Please refer to Table 1, which summarizes the composition ratios of the hemostatic materials described in Examples 1 to 5 of the present invention; please refer to FIG. 1, FIG. 1 shows that the hemostatic materials described in Examples 1 to 5 of the present invention are used to coagulate cell culture medium DMEM After (Dulbecco's Modified Eagle's medium), gel formation test in a 50mL centrifuge tube. The test conditions are that 1 gram of hemostatic material is evenly mixed with 20 mL of cell culture medium DMEM, and the gel formation time is recorded; the gel formation time is to shake the hemostatic material evenly. After DMEM with the cell culture medium, when the centrifuge tube is inverted, the colloid will not fall off. Example 1 Example 2 Example 3 Example 4 Example 5 hemostatic composition 20% 30% 60% 90% 100% Swelling agent 30% 30% 15% 4% 0% thickener 20% 15% 10% 3% 0% electrolyte 10% 10% 5% 3% 0% developer 20% 15% 10% 0% 0% gel time no glue 10 minutes 1 minute 30 seconds 3 minutes 30 seconds 5 minutes Table 1

As can be seen from Figure 1, Example 1 did not form a gel after mixing with the cell culture liquid, but was still liquid; the gel time of Example 2 was greater than 10 minutes, and it became a viscous gel, still fluid, and could not adhere when the centrifuge tube was inverted. At the bottom of the centrifuge tube, there is a situation of falling off; the gel time of Example 3 is 1 minute and 30 seconds. After inverting the centrifuge tube, it still adheres to the bottom of the centrifuge tube, and no falling off occurs. The gel time of Example 4 is 3 minutes and 30 minutes. Second, after inverting the centrifuge tube, it still adhered to the bottom of the centrifuge tube; in Example 5, the gel formation time was 5 minutes, and it still adhered to the bottom of the centrifuge tube after inverting the centrifuge tube. .

Experimental example 2

In this experimental example, about 20 mL of DMEM (Dulbecco's Modified Eagle's medium) medium was added to a 50 mL serum bottle, and a hemostatic material was prepared in a jet catheter device, and then 0.75~1.5 g of the hemostatic material was manually pressurized into the jet catheter device. Spray and deliver it to DMEM, and record the gelation time; in this experimental example, the gelation time is that after the hemostatic material is delivered to DMEM, the liquid level is no longer disturbed under the gas delivered by the jet catheter, and the gel is formed after the serum bottle is inverted. The DMEM adhered to the bottom of the serum bottle and did not fall off; in the air jet catheter device, prepare the hemostatic material described in Example 6, and manually pressurize the air jet catheter device. This time, 1 gram of the hemostatic material was delivered to the DMEM, about 5 gram of the hemostatic material. After ~20 seconds, the coagulation state of DMEM was observed; as shown in Figure 2, 15 seconds after the hemostatic material was delivered to the surface of DMEM, DMEM was completely coagulated under the action of the hemostatic material, and after the serum bottle was inverted, the formed gel still adhered to the surface of DMEM. The bottom of the serum bottle does not fall off.

Experimental example 3

In this experimental example, about 20 mL of fetal bovine serum (FBS, fetal bovine serum) was added to a 50 mL serum bottle, and a hemostatic material was prepared in a jet catheter device, and then 0.75~1.5 grams of hemostasis was added to manually pressurize the jet catheter device. The material was sprayed and delivered to the fetal bovine serum, and the gelation time was recorded; in this experimental example, the gelation time was after the hemostatic material was delivered to the fetal bovine serum, and the liquid level was no longer disturbed under the gas delivered by the jet catheter, and the serum bottle After inversion, the gel-forming fetal bovine serum adheres to the bottom of the serum bottle and does not fall off.

In the air jet catheter device, prepare the hemostatic material described in Example 6, and manually pressurize the air jet catheter device. This time, 1 gram of the hemostatic material is delivered to fetal bovine serum, and the coagulation of fetal bovine serum is observed after about 3 to 10 seconds. As shown in Figure 3, 6 seconds after the hemostatic material was delivered to the surface of the fetal bovine serum, the fetal bovine serum was completely coagulated under the action of the hemostatic material, and after the serum bottle was inverted, the formed gel still adhered to the bottom of the serum bottle. does not fall.

Experimental example 4

樣品 吸水倍率 樣品 吸水倍率 實施例1 1~5 實施例6 15~20 實施例2 1~5 Hemospray ^® 1~5 實施例3 15~20 Endoclot ^® 5~10 實施例4 5~10 HaemoCer ^TMPLUS 3~5 實施例5 5~10 - - 表2 The hemostatic materials described in Examples 1 to 6 of the present invention, Hemospray ^® (Cook Medical), Endoclot ^® (Endoclot Plus Inc.), and HaemoCer ^TM PLUS (BioCer Entwicklungs-GmbH) were measured for water absorption ratios, so as to compare the hemostasis provided by the present invention. The water absorption ratio of the material and the commercially available competing products, please refer to Table 2 for the results. The "water absorption rate" here refers to the maximum amount of water that a 1 gram sample can absorb, and its calculation method is simply expressed as follows:

sample Water absorption rate sample Water absorption rate Example 1 1~5 Example 6 15~20 Example 2 1~5 Hemospray ^® 1~5 Example 3 15~20 ^Endoclot® 5~10 Example 4 5~10 HaemoCer ^™ PLUS 3~5 Example 5 5~10 - - Table 2

As can be seen from Table 2, the water absorption ratio of Example 1 is 1 to 5 times, the water absorption ratio of Example 2 is 1 to 5 times, the water absorption ratio of Example 3 is 15 to 20 times, and the water absorption ratio of Example 4 is 5- 10 times, the water absorption rate of Example 5 is 5~10 times, the water absorption rate of Example 6 is 15~20 times, the water absorption rate of ^Hemospray® is 1~5 times, the water absorption rate of ^Endoclot® is 5~10 times, HaemoCer The water absorption ratio of ^TM PLUS is 3-5 times. It can be seen from this experimental example that the hemostatic materials prepared in Example 3 and Example 6 of the present invention are compared with commercially available hemostatic materials such as Hemospray ^® , Endoclot ^® , HaemoCer ^TM PLUS. Higher water absorption rate.

Experimental example 5

Prepare the hemostatic material, prepare a rubber hose, one end is connected to the pump to inject normal temperature water, the water contains red dye for easy observation, and the other end is ligated with a hemostatic forceps to test the anti-bleeding pressure strength of the hemostatic material. A 21-gauge needle was used to puncture a hole in the hose to simulate active bleeding from a ruptured blood vessel. Start the pump to inject water containing red dye, and observe the simulated bleeding. Next, use a syringe to hold the hemostatic material, push the syringe piston to spray about 3 grams of the hemostatic material to the bleeding site, and observe the hemostasis. Under the condition that the bleeding pressure reaches 180mmHg, the hemostatic material is sprayed into the hole for 3-30 seconds, the bleeding situation is controlled, and complete hemostasis is achieved.

Please refer to Table 3 to illustrate the time for the hemostatic materials prepared in each example to maintain hemostasis without leakage under the pressure of 180 mmHg; wherein, the hemostatic materials prepared in Examples 1 to 3 could not maintain hemostasis under the pressure of 180 mmHg , Example 4 maintained hemostasis for 10 minutes, Example 5 maintained hemostasis for 30 minutes, and Example 6 maintained hemostasis for 48 hours. Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 180mmHg to maintain hemostasis inability to maintain hemostasis inability to maintain hemostasis inability to maintain hemostasis 10 minutes 30 minutes 48 hours table 3

Experimental example 6

After being anesthetized with isoflurane, the tail ends of the rats in the control group (1 rat in total) and the experimental group (5 rats in total) were cut off by about 2 cm, respectively, and the bleeding was observed. In the control group, a 7cm×5cm×1cm hemostatic gauze was applied to the tail and the hemostasis was observed. Please refer to Figure 4. The experimental results show that the control group still oozes blood after continuous pressure with gauze for more than 1 minute. blood situation.

Experimental example 7

Evaluation of the hemostatic effect of the Lanyu pig gastric hemorrhage model

Animal breed: Lanyu pig

Quantity: 3

Weight: 25~30 kg

Age: 5~6 weeks

gender: male

Experimental method: Pigs were given anticoagulant drugs such as aspirin or clopidogrel for five consecutive days prior to the experiment; see Figure 5A, on the day of surgery, using endoscopy A gastric hemorrhage model of Forrest grade Ia (Active spurting, active spurting) or Ib (Active oozing) (Active oozing) was created on the stomach of pigs by electrocautery; see Figure 5B, the bleeding was observed after surgery, and sprayed 6 ~ 18g of the hemostatic material of Example 6 of the present invention to the bleeding site, successfully controlled the bleeding and achieved the effect of hemostasis; after 10 days of continuous observation, there were no obvious side effects or complications, such as arterial embolism, allergic reaction or intestinal obstruction. etc.; please refer to Figure 5C, 10 days after the operation, another endoscopy was performed to observe the recovery of the wound, and the tissue was taken to prepare pathological sections. Postoperative observation showed that the wound recovered in good condition, and no hemostatic material remained in the wound, and tissue sections showed no other pathological inflammatory reactions.

To sum up, the hemostatic material for preparing the hemostatic composition provided by the present invention has the following effects:

1. The hemostatic material provided by the present invention has a fast gel-forming speed, and can quickly form a gel and cover the wound after contacting with blood, so as to prevent the bleeding.

2. Compared with commercially available hemostatic materials such as Hemospray ^® , Endoclot ^® , HaemoCer ^TM PLUS, etc., the hemostatic material provided by the present invention exhibits a higher water absorption rate, which is helpful for absorbing a large amount of wounds under the condition of heavy bleeding. Water, to achieve coagulation of blood cells and coagulation factors to promote coagulation.

3. The hemostatic material provided by the present invention has good adhesion. In addition to quickly forming a colloid to cover the wound after contacting the blood, it also has high adhesion, so that the formed colloid can be firmly attached to the bleeding place to achieve hemostasis. Effect.

4. The hemostatic material provided by the present invention achieves the effect of hemostasis within 3-10 seconds, and in the back-end application, it can quickly absorb water even in the case of massive bleeding, so as to achieve the effect of promoting blood coagulation to stop bleeding.

5. The hemostatic material provided by the present invention can maintain the wound coverage under the condition of high bleeding pressure after covering the wound to promote coagulation, so as to achieve the effect of long-term hemostasis.

The hemostatic material for preparing the hemostatic composition provided by the present invention can achieve rapid and effective hemostasis in the following situations of bleeding:

1. Hemostasis in surgery.

2. Hemostasis of external trauma.

3. Hemostasis under endoscopy.

Specifically, for example, gastrointestinal bleeding, such as ulcers, mucosal damage, diffuse bleeding, bleeding caused by endoscopic submucosal dissection or endoscopic mucosal resection, the hemostatic material for preparing the hemostatic composition provided by the present invention can be obtained through The endoscopic catheter is applied to the bleeding place, the hemostatic material quickly gels after contacting the blood and achieves the effect of hemostasis, and the hemostatic material is made of a bioabsorbable material, which can be absorbed by the individual when applied to the gastrointestinal tract, and has no effect. Residual risk; in addition, the added contrast agent can assist the user to directly track the attachment position of the hemostatic powder with X-ray, so that the individual no longer has to endure the discomfort caused by endoscopy or surgery.

However, the above description is only a description of the preferred embodiments of the present invention, and those skilled in the art can make other various improvements according to the above description, but these changes still belong to the spirit of the present invention and the patent defined below in the range.

(none)

FIG. 1 is a diagram of the coagulation of DMEM culture medium, illustrating that Examples 1 to 5 of the hemostatic material of the present invention promote the coagulation and adhesion of DMEM culture medium. FIG. 2 is a diagram of the coagulation of DMEM culture fluid, illustrating that Example 6 of the hemostatic material of the present invention promotes the coagulation of DMEM culture fluid. 3 is a coagulation diagram of fetal bovine serum FBS, illustrating that Example 6 of the hemostatic material of the present invention promotes the coagulation of fetal bovine serum FBS. Figure 4 is a diagram of a rat tail docking hemostasis experiment, illustrating the comparison of the hemostatic effect of Example 6 of the hemostatic material of the present invention and conventional hemostatic gauze. Figure 5A is a picture of gastric hemorrhage of a Lanyu pig, showing the situation of Forrest grade Ib hemorrhage in the Lanyu pig gastric hemorrhage model. FIG. 5B is a diagram of the treatment of gastric hemorrhage in a Lanyu pig, showing the situation of hemostasis after Example 6 of the hemostatic material of the present invention is applied to the bleeding site. Fig. 5C is a picture of the healing of gastric hemorrhage in a Lanyu pig, showing the healing of the bleeding site on the 10th day after Example 6 of the hemostatic material of the present invention was applied to the site of bleeding.

Claims (10)

A hemostatic material for preparing a hemostatic composition and delivering it to a wound to achieve the effect of rapid hemostasis; Wherein, the hemostatic material includes: A hemostatic composition, which is a bioabsorbable water-absorbing material composed of natural source polysaccharides; and An excipient composition comprising a swelling agent, a thickening agent, an electrolyte and a developing agent, the swelling agent is a synthetic polymer substance, and the thickening agent is animal-derived protein, based on the total weight of the hemostatic material , the hemostatic material contains 30~99.9% (w/w) hemostatic composition, the excipient composition contains 0.1~30% (w/w) swelling agent, 0.1~15% (w/w) thickening agent agent, 0.1~10% (w/w) electrolyte and 0.1~20% (w/w) developer. The hemostatic material according to claim 1, wherein the hemostatic composition comprises guar gum, alginate, gellan gum, tragacanth, xanthan gum gum), Chitosan, Sodium starch glycolate, Sucrose, Sorbitol, Mannitol, Starch, Dextran or a combination thereof. The hemostatic material according to claim 2, wherein the swelling agent comprises Calcium polycarbophil, Polyethylene glycol, Polyethylene oxide, Poloxamers or a combination thereof. The hemostatic material according to claim 3, wherein the thickening agent comprises gelatin (Gelatin), collagen (Collagen) or a combination thereof. The hemostatic material according to claim 4, wherein the electrolyte comprises Calcium phosphate, Calcium chloride, Calcium lactate, Zinc acetate, Zinc oxide or the like combination. The hemostatic material according to claim 5, wherein the delivery treatment is delivered to the wound or around the wound by spraying, spraying or coating through a catheter or a solid carrier; the catheter is an endoscopic catheter, a laparoscopic catheter Or thoracoscopic catheter; the solid carrier is bandage, gauze or hemostatic cotton. The hemostatic material according to any one of claims 1 to 6, wherein the wound is caused by ulcers, mucosal damage, exposure of blood vessels, fistulas or surgery, and the surgery is esophagectomy, vascular anastomosis, endoscopic submucosal dissection or endoscopic surgery Endoscopic mucosal resection. The hemostatic material according to any one of claims 1 to 6, which achieves the effect of hemostasis within 3-10 seconds after the hemostatic material is delivered to the wound. According to the hemostatic material according to any one of claims 1 to 6, after the hemostatic material is delivered to the wound, hemostasis can be maintained for 5 minutes to 72 hours under the bleeding pressure of 150 to 210 mmHg. A use of the hemostatic material as described in any one of claims 1 to 6 for preparing a hemostatic composition, which is to deliver the composition to the wound of a desired individual with an effective dose of the hemostatic material to achieve the effect of hemostasis ; Wherein, the effective dose is 1.0~6.0 g/mm ² ; The wound is caused by ulcer, mucosal damage, vascular exposure, fistula or surgery, and the surgery is esophagectomy, vascular anastomosis, endoscopic submucosal dissection or endoscopy Mucosal resection; the hemostatic material is delivered to the wound to achieve hemostasis within 3 to 10 seconds; after the hemostatic material is delivered to the wound, under a bleeding pressure of 150 to 210 mmHg, hemostasis can be maintained for 5 minutes to 72 hours.

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