CN114404644A

CN114404644A - Medical adhesive and preparation method thereof

Info

Publication number: CN114404644A
Application number: CN202210065623.1A
Authority: CN
Inventors: 王明波; 敖鹏; 李木平; 田茂财; 谭荣伟; 佘振定
Original assignee: Shenzhen Lando Biomaterials Co ltd
Current assignee: Shenzhen Lando Biomaterials Co ltd
Priority date: 2022-01-20
Filing date: 2022-01-20
Publication date: 2022-04-29

Abstract

The invention relates to a medical adhesive and a preparation method thereof. The medical glue material stock solution comprises a reagent A, a reagent B and a reagent C, wherein the reagent A comprises a water-soluble polyhydroxy polymer with the concentration of 0.005-10 wt%, the reagent B comprises an aldehyde compound with the concentration of 0.001-8 wt%, the reagent C comprises a water-soluble protein with the concentration of 0.001-40 wt%, the sum of the concentration of the water-soluble polyhydroxy polymer and the concentration of the water-soluble protein is not less than 0.08 wt%, the pH of the reagent A is 0.01-7, the pH of the reagent B is 0.01-10, and the pH of the reagent C is 0.01-10. The medical adhesive has excellent adhesiveness, viscoelasticity and tolerance (acid-enzyme degradation period resistance) in a special digestive tract environment, and has the effects of adhering and closing digestive tract ulcer or wound surface, preventing bleeding and perforation of the ulcer or wound surface and promoting healing.

Description

Medical adhesive and preparation method thereof

Technical Field

The invention relates to the technical field of biological materials, in particular to a medical adhesive and a preparation method thereof.

Background

Peptic ulcer refers to ulcer occurring in the digestive tract, and is a type of frequently occurring disease, among which gastric ulcer and duodenal ulcer are the most common. There are various factors in the formation of peptic ulcer, and among them, attack of acidic gastric juice (pH 0.9 to 1.5) and digestive enzymes (e.g., pepsin) contained therein on mucosa is one of the factors. The expression "acid-free, i.e. ulcer-free". Any part contacted by the acidic gastric juice, such as the lower esophageal segment, the anastomotic stoma after gastrointestinal anastomosis and the jejunum, may cause ulcer.

At present, the peptic ulcer caused by acid gastric juice and digestive enzymes is mainly treated by medicaments, wherein the medicaments comprise anti-ulcer medicaments (proton pump inhibitors, H2 receptor blockers and the like), mucosa protective agents (bismuth preparations, aluminum salt preparations and the like), antibiotics, antibiotic-containing preparations, gastric motility medicaments and the like. According to statistics, the market share of the anti-ulcer drug and the mucosa protective agent in the traditional Chinese medicine hospital, the western medicine hospital and the pharmacy is 56.86%, 69.17% and 61.05% respectively. However, the mucosa protective agent has the defects of limited protective effect on the mucosa of the focus, easy loss, short protective time-effect and need to be taken on time every day.

Another type of factors that form peptic ulcers are defective wounds that result from Endoscopic Mucosal Resections (EMR), endoscopic mucosal dissection (ESD), oral endoscopic myotomies, endoscopic submucosal tunnel resections, etc. of early cancers, tumors, polyps, etc., and are characterized by: (1) the operation directly destroys mucous membrane to form 'artificial ulcer' in a short time; (2) the wound surface is deeper and has larger area than the common peptic ulcer, and can reach the muscular layer integrally; (3) the wound surface part is not limited to the antrum, the lesser curvature of the stomach, the lower part of the stomach and the like with good peptic ulcer, but also can be generated in the regions with relatively less acid secretion in the stomach, such as the upper part of the stomach, the fundus and the like; (4) the wound repair process may not be accompanied by an increase in gastric acid secretion. Among the postoperative complications of EMR and ESD are bleeding and perforation caused by unclosed mucosal wound, and even normal healing is affected. At this time, the wound surface is often closed by a metal clip (such as a titanium clip) or a metal clip combined with a nylon cord, so as to reduce bleeding and perforation during and after the operation. The metal clip or the metal clip combined nylon rope method has the action principle that the focus and the surrounding normal mucous membrane are clipped together through mechanical action to close the wound surface and the blood vessel, so as to prevent perforation and bleeding, protect the wound surface from being corroded by gastric acid and enzyme to a certain extent, and reduce the risk of perforation and bleeding. However, the metal clip has disadvantages in that: difficult closing operation, easy falling (generally falling about 1 week), incomplete wound surface closure still corroded by gastric acid and enzyme, and large-size and irregular wound surface difficult application.

Disclosure of Invention

Therefore, the medical adhesive has excellent adhesiveness, viscoelasticity and acid enzyme tolerance, and can play roles in preventing bleeding and perforation and promoting healing due to the excellent adhesiveness, viscoelasticity and acid enzyme tolerance when being applied to digestive tract ulcer or digestive tract wound surface protection, so that the problem of poor treatment effect caused by easy loss or falling off of traditional medicines or devices for treating ulcer is solved.

A medical adhesive is characterized in that a material stock solution used by the medical adhesive comprises a reagent A, a reagent B and a reagent C, wherein the reagent A comprises a water-soluble polyhydroxy polymer with the concentration of 0.005-10 wt%, the reagent B comprises an aldehyde compound with the concentration of 0.001-8 wt%, and the reagent C comprises a water-soluble protein with the concentration of 0.001-40 wt%, wherein the sum of the concentration of the water-soluble polyhydroxy polymer and the concentration of the water-soluble protein is not less than 0.08 wt%. The pH of the reagent A is 0.01-7, the pH of the reagent B is 0.01-10, and the pH of the reagent C is 0.01-10.

In one embodiment, the medical adhesive has a bonding strength of 20kPa to 1300 kPa.

In one embodiment, the acid-resistant enzyme degradation period of the medical adhesive is 3 days to 31 days.

In one embodiment, the water-soluble protein is selected from at least one of serum albumin, egg white protein, serum globulin, concanavalin a, water-soluble glycoprotein, and collagen;

and/or, the water-soluble polyhydroxy polymer is selected from at least one of polyvinyl alcohol, chitosan and xanthan gum;

and/or, the aldehyde compound is at least one selected from formaldehyde, glyoxal, malonaldehyde, glutaraldehyde, adipaldehyde, methylglyoxal and terephthalaldehyde.

In one embodiment, the agent a further comprises at least one of polyethylene glycol, a polyethylene glycol derivative, an antibacterial agent, and a water-soluble inorganic salt; the sum of the concentration of the polyethylene glycol and the concentration of the polyethylene glycol derivative is 0.001 wt% -10 wt%; the concentration of the antibacterial agent is 0.00001 wt% -2 wt%; the concentration of the water-soluble inorganic salt is 0.001-5 wt%;

and/or the reagent C also comprises at least one of water-soluble amino acid, water-soluble polypeptide, diamine derivative, binding polymer and pigment, wherein the binding polymer is a polymer obtained by polymerization reaction of a polyol compound, a polycarboxylic acid compound and a polyphenol compound; the concentration of the water-soluble amino acid is 0.0001 wt% -5 wt%; the concentration of the water-soluble polypeptide is 0.001-1 wt%; the sum of the concentrations of the diamine and the diamine derivative is 0.001 to 2 weight percent; the concentration of the binding polymer is 0.001 wt% -40 wt%; the concentration of the pigment is 0.0001 wt% -0.1 wt%.

In one embodiment, the diamine is selected from at least one of ethylenediamine, propylenediamine, and butylenediamine;

and/or, the diamine derivative is selected from at least one of ethylenediamine tetraacetic acid and ethylenediamine diacetic acid;

and/or, the water-soluble polypeptide is selected from at least one of soybean polypeptide, casein phosphopeptide, corn peptide and glutathione;

and/or, the water-soluble amino acid is selected from at least one of serine, threonine, cysteine, glutamic acid, aspartic acid, arginine, lysine and histidine;

and/or, the antibacterial agent is selected from at least one of amoxicillin, mebendazole, levofloxacin, tetracycline, soluble silver salt and potassium sorbate;

and/or the weight-average molecular weight of the polyethylene glycol is 200 Da-8000 Da;

and/or the polyethylene glycol derivative is selected from at least one of four-arm PEG with the weight-average molecular weight of 400 Da-10000 Da, four-arm PEG sulfydryl with the weight-average molecular weight of 600 Da-5000 Da, four-arm PEG amino with the weight-average molecular weight of 400 Da-6000 Da and six-arm PEG amino with the weight-average molecular weight of 2000 Da-20000 Da;

and/or, the water-soluble inorganic salt is selected from at least one of sodium chloride, potassium chloride, sodium acetate, potassium acetate, sodium phosphate and potassium phosphate;

and/or the pigment is brilliant blue, methylene blue or indigo carmine.

In one embodiment, the ratio of the used mass of the reagent A, the reagent B and the reagent C is (1-5): 1: (1-5).

In one embodiment, the medical gel is a gel for digestive tract ulcers or digestive tract wounds.

The preparation method of the medical adhesive comprises the following steps: and mixing the reagent A, the reagent B and the reagent C to prepare the medical adhesive.

In one embodiment, the agent A, the agent B and the agent C are mixed under a digestive endoscope by using a sprayer, wherein the sprayer comprises a storage barrel, an inner handle, an outer handle and a double sleeve;

the storage cylinder is provided with a plurality of independent storage cavities and pistons matched with the storage cavities;

the inner handle is provided with a mixing pipe, one end of the inner handle can be in sealed butt joint with the discharge end of the storage barrel so that the material liquid in different storage cavities can enter the mixing pipe to be mixed uniformly, and the other end of the inner handle can be inserted into the outer handle;

the outer handle is provided with a sleeve, an air cavity part and an outer pipe joint which are sequentially arranged, the mixing pipe can be inserted into the inner handle, the far end of the mixing pipe can be hermetically connected with the outer handle so as to seal one end of the air cavity part, and the air cavity part is provided with an air pipe joint communicated with an inner air cavity of the air cavity part;

the proximal end of the double sleeve can be connected with the outer pipe joint;

the sprayer is provided with a liquid flow passage and a gas flow passage, the liquid flow passage comprises a flow passage part formed by matching the mixing pipe and the inner pipe of the double sleeve, the gas flow passage comprises a flow passage part formed by matching the outer pipe of the double sleeve and the gas cavity, and the liquid flow passage and the gas flow passage are narrowed at the far end;

the reagent A, the reagent B and the reagent C are respectively positioned in different storage cavities.

Drawings

FIG. 1 is a perspective view of an embodiment of a sprinkler;

FIG. 2 is a perspective view of the sprinkler shown in FIG. 1 from another perspective;

FIG. 3 is a perspective view of another perspective of the sprinkler shown in FIG. 1;

FIG. 4 is an exploded view of the sprinkler shown in FIG. 1;

FIG. 5 is a cross-sectional view of the sprinkler shown in FIG. 1;

FIG. 6 is a perspective view of the push rod of the sprinkler shown in FIG. 1;

FIG. 7 is a perspective view of a sealing plug of the sprinkler shown in FIG. 1;

FIG. 8 is a perspective view of a storage cartridge of the sprinkler shown in FIG. 1;

FIG. 9 is a perspective view of a reservoir cartridge of a sprinkler of another embodiment;

FIG. 10 is a perspective view of the sealing sleeve of the sprinkler shown in FIG. 1;

FIG. 11 is a perspective view of the inner handle of the sprayer shown in FIG. 1;

FIG. 12 is a cross-sectional view of the inner handle of FIG. 11;

FIG. 13 is a perspective view of the outer handle of the sprayer shown in FIG. 1;

FIG. 14 is a cross-sectional view of the external handle of FIG. 13;

FIG. 15 is a partial view of the double sleeve of the sprinkler shown in FIG. 1;

FIG. 16 is an enlarged view of a portion of the sprinkler shown in FIG. 1;

fig. 17 is an exploded view of another embodiment sprinkler;

FIG. 18 is a perspective view of a flow restricting fitting of the sprinkler shown in FIG. 1;

FIG. 19 is an enlarged view of portion A of the flow restricting fitting shown in FIG. 5;

fig. 20 is an exploded view of another embodiment sprinkler;

fig. 21 is an exploded view of another embodiment sprinkler;

FIG. 22 is a cross-sectional view of the sprinkler shown in FIG. 21;

fig. 23 is an enlarged view of part B of the sprinkler of fig. 22.

Reference numerals:

10. a sprinkler; 111. a gas jet; 121. a storage cylinder; 122. a piston; 122a, a sealing plug; 122b, a push rod; 130. sealing sleeves; 131. a material aperture; 140. a capillary tube; 150. an inner handle; 151. a conical head structure; 152. a hand-held portion; 153. the elastic clamping piece; 154. mounting a column; 155. a mixing core; 160. an outer handle; 161. a card slot; 162. a guide groove; 163. a gas pipe joint; 180. a seal ring; 170. double-casing; 171. an inner tube; 172. an outer tube; 173. a supporting strip; 190. a current limiting junction; 175. a closing-in part; 20. is externally connected with an air pipe.

Detailed Description

The present invention will now be described more fully hereinafter for purposes of facilitating an understanding thereof, and may be embodied in many different forms and are not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may be present. When the terms "vertical," "horizontal," "left," "right," "upper," "lower," "inner," "outer," "bottom," and the like are used to indicate an orientation or positional relationship, it is for convenience of description only based on the orientation or positional relationship shown in the drawings, and it is not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present application. The term "and/or" includes any and all combinations of one or more of the associated listed items. Further, "proximal" and "distal" are terms of orientation, wherein "proximal" refers to the end that is closer to the operator during the procedure; "distal" means the end away from the operator.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

An embodiment of the application provides a medical adhesive, wherein a material stock solution of the medical adhesive comprises a reagent A, a reagent B and a reagent C, the reagent A comprises a water-soluble polyhydroxy polymer with the concentration of 0.005 wt% -10 wt%, the reagent B comprises an aldehyde compound with the concentration of 0.001 wt% -8 wt%, the reagent C comprises a water-soluble protein with the concentration of 0.001 wt% -40 wt%, the sum of the concentration of the water-soluble polyhydroxy polymer in the reagent A and the concentration of the water-soluble protein in the reagent C is not less than 0.08 wt%, the pH of the reagent A is 0.01-7, the pH of the reagent B is 0.01-10, and the pH of the reagent C is 0.01-10.

The medical glue is prepared by reacting the reagent A, the reagent B and the reagent C to generate the hydrogel type medical glue. When the reagent A, the reagent B and the reagent C react, an aldehyde compound in the reagent B is used as a cross-linking agent, and the aldehyde compound and a water-soluble polyhydroxy Polymer in the reagent A and a water-soluble protein in the reagent C simultaneously undergo Schiff base reaction and acetal reaction respectively to form the hydrogel type medical adhesive with an Interpenetrating Polymer Networks (IPN). In addition, the addition of the water-soluble protein is also beneficial to improving the adhesiveness and the hemostatic performance of the medical adhesive.

It should be noted that, unless otherwise specified, the concentrations in the present specification are all used concentrations. For example, the water-soluble polyhydroxypolymer having a concentration of 0.005 to 10% by weight means that the concentration of the water-soluble polyhydroxypolymer in the reagent A is 0.005 to 10% by weight when the reagent A, the reagent B and the reagent C are mixed. The use of the aldehyde compound at a concentration of 0.001 to 8 wt% means that the concentration of the aldehyde compound in the reagent B is 0.001 to 8 wt% when the reagent A, the reagent B and the reagent C are mixed.

Alternatively, the water-soluble polyhydroxy polymer comprises at least one of a water-soluble synthetic polyhydroxy polymer and a water-soluble natural polyhydroxy polymer. In some embodiments, the water-soluble polyhydroxy polymer is selected from at least one of polyvinyl alcohol, chitosan, and xanthan gum.

In an alternative specific example, the concentration of the water-soluble polyhydroxy polymer is 0.005 wt%, 0.01 wt%, 0.02 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 2.5 wt%, 5 wt%, 6 wt%, 7.5 wt%, or 10 wt%. Further, the concentration of the water-soluble polyhydroxy polymer is 0.01 wt% to 7.5 wt%. Further, the concentration of the water-soluble polyhydroxy polymer is 0.02 wt% to 6 wt%.

In an alternative specific example, the pH of agent a is 0.01, 0.1, 1, 2.5, 3.5, 4, 4.5, 5, 5.5, 6, or 7. Further, the pH of the reagent A is 0.1-7.

Optionally, the aldehyde compound is selected from at least one of formaldehyde, glyoxal, malondialdehyde, glutaraldehyde, adipaldehyde, methylglyoxal, and terephthalaldehyde. It is to be understood that, in other embodiments, the aldehyde compound is not limited to the above, and may be other aldehyde group-containing compounds.

In an alternative specific example, the pH of the B agent is 0.01, 0.1, 1, 2.5, 3.5, 4, 4.5, 5, 5.5, 6, or 7. Further, the pH of the reagent B is 0.5-7.

In some embodiments, the water-soluble protein is selected from at least one of serum albumin, ovalbumin, serum globulin, concanavalin a, water-soluble glycoproteins, and collagen. In an alternative specific example, the concentration of the water-soluble protein is 0.001 wt%, 0.005 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 4 wt%, 5 wt%, 8 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, or 40 wt%. Further, the concentration of the water-soluble protein is 0.05 wt% to 30 wt%. Furthermore, the concentration of the water-soluble protein is 0.05 wt% to 20 wt%.

In some embodiments, the ratio of the mass of reagent A, reagent B and reagent C is (1-5): 1: (1-5). Setting the ratio of the used mass of the reagent A, the reagent B and the reagent C as (1-5): 1: (1-5), the adhesive property and the viscoelasticity of the prepared medical adhesive can be improved. Furthermore, the ratio of the used mass of the reagent A, the reagent B and the reagent C is (1-4): 1: (1-4).

In some embodiments, the agent a further comprises at least one of polyethylene glycol, a polyethylene glycol derivative, an antibacterial agent, and a water-soluble inorganic salt.

Polyethylene glycol (PEG) and polyethylene glycol derivatives have crosslinkable groups, further more short-range crosslinking points are formed, and the improvement of the viscoelasticity of the medical adhesive is facilitated. In some embodiments, the polyethylene glycol has a weight average molecular weight of 200Da to 8000 Da. In some embodiments, the polyethylene glycol derivative is selected from at least one of a four-arm PEG with a weight average molecular weight of 400Da to 10000Da, a four-arm PEG sulfhydryl with a weight average molecular weight of 600Da to 5000Da, a four-arm PEG amino with a weight average molecular weight of 400Da to 6000Da, and a six-arm PEG amino with a weight average molecular weight of 2000Da to 20000 Da. It is to be understood that the polyethylene glycol derivative is not limited to the above.

In some embodiments, the sum of the concentration of polyethylene glycol and the concentration of polyethylene glycol derivative is 0.001 wt% to 10 wt%. In an alternative specific example, the sum of the concentration of polyethylene glycol and the concentration of polyethylene glycol derivative is 0.001 wt%, 0.005 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2.5 wt%, 5 wt%, 7.5 wt%, or 10 wt%. Furthermore, the sum of the concentration of the polyethylene glycol and the concentration of the polyethylene glycol derivative is 0.005 wt% -7.5 wt%. Furthermore, the sum of the concentration of the polyethylene glycol and the concentration of the polyethylene glycol derivative is 0.01 wt% -5 wt%.

The antibacterial agent is used for preventing microorganisms from breeding in a gel preparation reagent in the production and transportation processes, and is also used as a medicine for preventing wound infection. In one embodiment, the antimicrobial agent is selected from at least one of an antibiotic, a soluble silver salt, and potassium sorbate. In an alternative embodiment, the antibiotic is selected from at least one of amoxicillin, mebendazole, levofloxacin antibiotics (e.g., levofloxacin hydrochloride), and tetracycline antibiotics (e.g., tetracycline hydrochloride). It is understood that in other embodiments, the antibiotic is not limited to the above.

In some embodiments, the concentration of the antimicrobial agent is 0.00001 wt% to 2 wt%. In an alternative specific example, the concentration of the antimicrobial agent is 0.0001 wt%, 0.005 wt%, 0.001 wt%, 0.005 wt%, 0.01 wt%, 0.5 wt%, 1 wt%, or 2 wt%. Further, the concentration of the antibacterial agent is 0.005 wt% to 2 wt%. Further, the concentration of the antibacterial agent is 0.02 wt% to 2 wt%.

The water-soluble inorganic salt can adjust the ionic strength of the mixed reagent at the initial stage of the reaction and the ionic environment of the reaction. In some embodiments, the water-soluble inorganic salt is selected from at least one of sodium chloride, potassium chloride, sodium acetate, potassium acetate, sodium phosphate, and potassium phosphate. It is to be understood that in other embodiments, the water-soluble inorganic salt is not limited to the above. In some embodiments, the concentration of the water-soluble inorganic salt is 0.001 wt% to 5 wt%. In an alternative specific example, the concentration of the water-soluble inorganic salt is 0.001 wt%, 0.05 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3.5 wt%, or 5 wt%. Further, the concentration of the water-soluble inorganic salt is 0.05 wt% to 3.5 wt%. Further, the concentration of the water-soluble inorganic salt is 0.05 wt% to 1 wt%.

In some embodiments, the C reagent further comprises at least one of a water soluble amino acid, a water soluble polypeptide, a diamine derivative, an adhesive polymer, and a pigment. It is to be understood that at least one of the water-soluble amino acid, the water-soluble polypeptide, the diamine derivative, the binding polymer, and the pigment is not limited to being contained in the reagent C, and may be contained in the reagent a, or both the reagent a and the reagent C depending on the coexistence stability and the nature of the components.

The water-soluble amino acid has crosslinkable amino groups, further forms more short-range crosslinking points, and is favorable for improving the viscoelasticity of the medical adhesive. In some embodiments, the water soluble amino acid is selected from at least one of serine, threonine, cysteine, glutamic acid, aspartic acid, arginine, lysine, and histidine. It is understood that in other embodiments, the water-soluble amino acids are not limited to those described above. In some embodiments, the concentration of the water-soluble amino acid is 0.0001 wt% to 5 wt%. In an alternative specific example, the concentration of the water-soluble amino acid is 0.0001 wt%, 0.005 wt%, 0.001 wt%, 0.005 wt%, 0.01 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3.5 wt%, or 5 wt%. Further, the concentration of the water-soluble amino acid is 0.005 wt% -5 wt%. Further, the concentration of the water-soluble amino acid is 0.02 wt% to 5 wt%.

In some embodiments, the water-soluble polypeptide is selected from at least one of soy polypeptide, casein phosphopeptide, corn peptide, and glutathione. It is understood that in other embodiments, the water-soluble polypeptide is not limited to the above. In an alternative specific example, the concentration of the water-soluble polypeptide is 0.001 wt%, 0.003 wt%, 0.005 wt%, 0.08 wt%, 0.01 wt%, 0.05 wt%, 0.08 wt%, 0.1 wt%, 0.5 wt%, or 1 wt%. Further, the concentration of the water-soluble polypeptide is 0.005 wt% -1 wt%. Furthermore, the concentration of the water-soluble polypeptide is 0.01 wt% to 1 wt%.

The diamine and the diamine derivative have crosslinkable amino groups, further more short-range crosslinking points are formed, and the improvement of the viscoelasticity of the medical adhesive is facilitated. In some embodiments, the diamine is selected from at least one of ethylene diamine, propylene diamine, and butylene diamine. In some embodiments, the diamine derivative is selected from at least one of ethylenediaminetetraacetic acid and ethylenediamine diacetic acid. It is understood that in other embodiments, diamines and diamine derivatives are not limited to those described above. In some embodiments, the sum of the concentration of diamine and the concentration of diamine derivative is from 0.001 wt% to 2 wt%. In an alternative specific example, the sum of the concentration of diamine and the concentration of diamine derivative is 0.001 wt%, 0.003 wt%, 0.005 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.3 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, or 2 wt%. Further, the sum of the concentration of the diamine and the concentration of the diamine derivative is 0.01 to 2% by weight. Further, the sum of the concentration of the diamine and the concentration of the diamine derivative is 0.1 to 2% by weight.

The adhesive polymer is obtained by polymerizing a polyol compound, a polycarboxylic acid compound and a polyphenol compound. After the condensation polymerization reaction of the adhesive polymer and the aldehyde compound, the polyphenol hydroxyl group which is an adhesive functional group is connected into the network, so that the adhesive property of the medical adhesive is further enhanced. In some embodiments, the polyol compound includes at least one of an alcohol compound containing a plurality of hydroxyl groups and a polymer containing a plurality of hydroxyl groups. Optionally, the alcohol compound containing a plurality of hydroxyl groups is at least one selected from the group consisting of glycerin, glycerin derivatives, xylitol derivatives, sorbitol, and sorbitol derivatives. Optionally, the polymer containing a plurality of hydroxyl groups is selected from at least one of polyethylene glycol, polyethylene glycol derivatives, multi-armed polyethylene glycol derivatives, polyglycerol derivatives, polypentaerythritol, and polypentaerythritol derivatives. It is understood that, in other embodiments, the polyol compound is not limited to the above, and may be other compounds having a plurality of alcoholic hydroxyl groups.

In some embodiments, the polycarboxylic acid compound is selected from at least one of tartaric acid, tartaric acid derivatives, oxalic acid derivatives, malic acid derivatives, citric acid derivatives, ascorbic acid, and ascorbic acid derivatives. It is to be understood that, in other embodiments, the polycarboxylic acid compound is not limited to the above, and may be other compounds having a plurality of carboxyl groups.

In some embodiments, the polyphenol compound is selected from at least one of catechol, a catechol derivative, pyrogallol, a pyrogallol derivative, dopamine, a dopamine derivative, caffeic acid, a caffeic acid derivative, gallic acid, a gallic acid derivative, a catechin derivative, tannic acid, and a tannic acid derivative. It is to be understood that, in the examples, the polyphenol compound is not limited to the above, and may be other compounds having a plurality of phenolic hydroxyl groups.

In some embodiments, the preparation of the binding polymer comprises the steps of: the adhesive polymer is prepared by mixing a polyol compound, a polycarboxylic acid compound and a polyphenol compound, heating and melting the mixture under the protection of inert gas, and then adding a catalyst to carry out polymerization reaction. Optionally, the temperature for heating and melting is 105 ℃ to 250 ℃. After the polymerization reaction is finished, the method also comprises the step of purifying the crude product to remove unreacted substances.

In an alternative specific example, the concentration of the binding polymer is 0.001 wt%, 0.01 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 5 wt%, 8 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, or 40 wt%. Further, the concentration of the binding polymer is 0.01 wt% to 30 wt%. Further, the concentration of the binding polymer is 0.5 wt% to 20 wt%.

In some embodiments, the weight average molecular weight of the binding polymer is from 800Da to 50000 Da. Further, the weight average molecular weight of the binder polymer is 2000Da to 20000 Da.

In some embodiments, the pigment is brilliant blue, methylene blue, or indigo carmine. It is understood that in other embodiments, the pigment is not limited to the above.

In some embodiments, the medical gel further comprises a pH adjuster. The pH regulator is used for regulating the pH of the material stock solution in the medical glue. In one embodiment, the pH adjusting agent is selected from at least one of strong acids (e.g., hydrochloric acid, sulfuric acid, etc.) and strong bases (e.g., sodium hydroxide, potassium hydroxide, etc.). It is to be understood that in other embodiments, the pH adjusting agent is not limited to the above.

The medical adhesive has excellent adhesiveness, viscoelasticity and acid enzyme resistance. Specifically, the medical adhesive has a bonding strength of 20kPa to 1300 kPa. The medical adhesive has better viscoelasticity under the bonding strength, and after bonding, the medical adhesive wriggles along with the wriggling of the bonding substrate and is not easy to fall off from the wriggling bonding substrate. Further, the medical adhesive has a bonding strength of 460 to 1300 kPa. The excellent enzyme tolerance of the medical glue is shown as follows: the degradation period (acid-resistant enzyme degradation period) in gastric juice is 3 to 31 days. In this period, the medical glue plays a role in preventing the digestive tract ulcer or the bleeding and perforation of the digestive tract wound surface and promoting the healing. As used herein, peptic ulcer refers to naturally occurring peptic ulcer; the digestive tract wound surface refers to a defective wound surface generated after endoscopic mucosal resection, endoscopic mucosal dissection, oral endoscopic myotomy, endoscopic submucosal tunnel resection and the like of early cancer, tumor, polyp and the like. Furthermore, the degradation period of the medical glue in gastric juice is 20 to 31 days. It is understood that the gastric fluid may be artificial gastric fluid.

When the medical adhesive is used, the hydrogel type medical adhesive is prepared by mixing the reagents of the medical adhesive. Specifically, when the components in the above-mentioned reagents are dry powders or other solid preparations, the reagents are mixed with water at the concentrations of the reagents to prepare a gel. When the above-mentioned reagents are liquid preparations, hydrogel type medical gels are prepared by mixing the reagents. It can be understood that when all the reagents are packaged according to the use proportion, the reagents can be directly mixed to prepare the hydrogel type medical adhesive; when the reagents are not packaged according to the use proportion, the reagents are mixed according to the use proportion to prepare the hydrogel type medical adhesive.

It can be understood that the medical adhesive has excellent adhesiveness and viscoelasticity, and particularly can be applied to the field in which the viscoelasticity is required to be maintained after clinical adhesion and the medical adhesive does not fall off along with peristalsis, and can also be applied to the field in which the digestive tract requires an enzyme-tolerant environment. In some implementations, the medical gel is used for protecting a digestive tract ulcer or a digestive tract surgical wound. In some implementations, the alimentary tract surgery is an alimentary tract endoscopic surgery, such as EMR or ESD, and the like. It is understood that the medical gel is not limited to the use in the digestive tract, and may be used in other locations.

The medical adhesive at least has the following advantages:

(1) the medical adhesive is hydrogel with an interpenetrating polymer network structure, has good adhesiveness and viscoelasticity, can creep along with the creep of a bonded wound, has strong adhesive force, and is not easy to fall off from the wound.

(2) The medical glue has good acid enzyme tolerance (acid resistance and digestive enzyme degradation), gastric juice corrosion resistance and acid enzyme degradation resistance period of at least three days. The application environment of the medical glue comprises the whole digestive tract. The peristalsis and friction kinetic environment of the digestive tract including the upper and lower digestive tracts and the more remarkable environmental characteristics of high acidity (pH 0.9-1.5) and digestive enzymes (such as pepsin and the like) in the stomach. The medical adhesive is suitable for treating wounds of peptic ulcer and postoperative wounds of peptic ESD, EMR and the like. Compared with mucosa protective agent, the preparation has longer protective time-effect, and does not need to be taken on time every day. It is understood that resistance to a particular environment in the digestive tract is one of its technical effects, but not limiting other indications.

(3) The gel prepared by the medical gel can be used as a medical gel, and can physically press a wound surface due to the adhesiveness and the closure of the gel, so that the gel has the effect of preventing bleeding, and meanwhile, the mechanical closure of the wound surface prevents the wound surface from being eroded by gastric acid and digestive enzyme, and prevents perforation. Of course, when the gel also contains a hemostatic component, the hemostatic effect is better. In addition, due to good closing and protecting effects of the gel on the wound surface, pain and discomfort of a patient can be relieved, interference of gastric acid and digestive enzymes in the digestive tract on wound surface healing can be relieved, and healing of a focus can be promoted. Compared with a metal clamp, the metal clamp has the advantages that: the wound surface is not easy to fall off, the operation is more convenient, the wound surface is closed more tightly, and the wound surface can be applied to large-size wound surfaces, irregular wound surfaces and wound surfaces which can not be clamped due to pathological changes such as edema and the like which can not be suitable for the metal clamp.

In addition, an embodiment of the present application further provides a preparation method of the medical adhesive according to any one of the above embodiments, including the following steps: and mixing the reagent A, the reagent B and the reagent C to prepare the medical adhesive.

In some embodiments, the agent a, the agent B, and the agent C are mixed, transported, and sprayed under the digestive endoscope using a sprayer. Alternatively, referring to fig. 1-5, in some embodiments, the sprayer used when using the medical adhesive described above is sprayer 10. Specifically, sprayer 10 includes a storage barrel 121, an inner handle 150, an outer handle 160, and a double cannula 170; the storage cylinder 121 is provided with a plurality of independent storage cavities and pistons 122 matched with the storage cavities; the inner handle 150 is provided with a mixing pipe, one end of the inner handle 150 can be in sealed butt joint with the discharge end of the storage barrel 121 so that the material liquid in different storage cavities can enter the mixing pipe to be mixed uniformly, and the other end of the inner handle can be inserted into the outer handle 160; the outer handle 160 is provided with a sleeve, an air cavity part and an outer pipe joint which are arranged in sequence, the mixing pipe can be inserted into the sleeve, the far end of the mixing pipe can be hermetically connected with the sleeve to seal one end of the air cavity part, and the air cavity part is provided with an air pipe joint 163 communicated with an air cavity inside the air cavity part; the proximal end of the outer tube 172 of the double cannula 170 can be connected to an outer tube fitting; the sprinkler 10 has a liquid flow passage including a flow passage portion formed by a mixture pipe fitted with an inner pipe 171 of a double sleeve 170 and a gas flow passage including a flow passage portion formed by an outer pipe 172 of the double sleeve 170 fitted with an air chamber, the liquid flow passage and the gas flow passage being narrowed at distal ends.

The sprayer 10 is communicated with the mixing pipe of the inner handle 150 through the inner pipe 171 of the double sleeve 170 to form a liquid flow passage, the outer pipe 172 of the double sleeve 170 is communicated with the air cavity to form an air flow passage, and the liquid flow passage and the air flow passage are narrowed at the distal end, so that the sprayer 10 has spraying force capable of spraying in any direction, and compressed air (such as compressed air and compressed CO) entering from the air pipe joint 163 is enabled to enter₂Or other compressed medical gas) can drive the liquid medicine or the material stock solution to be sprayed out from the far end of the liquid flow passage without being influenced by gravity,can be sprayed to any direction, solves the problem that the liquid medicine or the material stock solution with high viscosity (for example, 50 mPa.s-400 mPa.s) can only be extruded out one drop at the tail end of the pipeline even under the condition of pressurization, and leads the focus which is not in the gravity direction to be sprayed to the liquid medicine or the material stock solution. In addition, the sprayer 10 has a spraying force capable of controllably spraying a liquid medicine or a material stock solution having a relatively low viscosity at a precise and stable rate.

Specifically, the material storage cavity of the material storage cylinder 121 is used for storing the material liquid; the piston 122 facilitates the extrusion of feed liquid from the storage chamber. The piston 122 includes a sealing plug 122a and a push rod 122b, the sealing plug 122a is fixed to the push rod 122b, the sealing plug 122a is closer to the discharge end of the storage barrel 121 than the push rod 122b, and the piston 122 can move in the storage barrel 121 along the axial direction of the storage barrel 121. Material enters or exits the storage barrel 121 by movement of the piston 122 in the storage barrel 121. It will be appreciated that movement of the piston 122 in a direction adjacent the outlet of the accumulator 121 facilitates the flow of material out of the sprinkler 10. Of course, the sealing plug 122a is connected to the storage cylinder 121 in a sealing manner, so that the storage cylinder 121 has good air tightness and can push the material out of the storage cylinder in proportion under a large pressure without leakage.

Referring to fig. 4, 6, 7 and 8, in some embodiments, the accumulator cartridge 121 has multiple independent accumulator chambers. Through the arrangement of a plurality of independent storage cavities, spraying after mixing of multiple components (such as multiple solutions) can be realized. Of course, the number of pistons 122 is adapted to the number of storage chambers. In the illustrated embodiment, the accumulator cartridge 121 has three accumulator chambers. Correspondingly, the number of the pistons 122 is three, three pistons 122 are respectively located in the three storage chambers, and the proximal ends of the three pistons 122 are connected with each other. By connecting the proximal ends of the three pistons 122 to each other, the movement of each piston 122 is uniform and can be moved in the axial direction of the storage cylinder 121 at the same time. It is understood that in other embodiments, the number of the storage chambers of the storage cylinder 121 and the number of the pistons 122 are not limited to three, and the specific number can be set according to practical situations. Such as one, two, four or five, etc. Of course, the piston 122 may also be provided independently. When the three pistons 122 are independently arranged, each piston 122 is independently movable. It will be appreciated that in some embodiments, the piston 122 may be omitted. When the piston 122 is omitted, the material in the storage cylinder 121 can be moved towards the mixing tube by other means (e.g., by pressurizing the storage cylinder 121).

In the embodiment shown in FIG. 4, the accumulator cartridge 121 and the accumulator chamber are both cylindrical. It will be appreciated that in other embodiments, the shape of the accumulator cartridge 121 and the accumulator chamber is not limited to cylindrical, but may be other shapes.

Specifically, the inner handle 150 is used to communicate the reservoir 121 with the inner tube 171, supplying the liquid to the distal end of the sprayer 10; outer handle 160 is used to introduce compressed gas for flow through outer tube 172 toward the distal end of sprinkler 10. In some embodiments, the proximal end of the inner handle 150 is sealingly connected to the discharge end of the cartridge 121 by a snap-fit arrangement. In the embodiment shown in fig. 8, the proximal end of the inner handle 150 is snap-fit connected to the discharge end of the storage cartridge 121 for ease of use. In the embodiment shown in fig. 9, the outlet of the accumulator cartridge 121 is designed as a boss. It will be appreciated that in other embodiments, the connection of the inner handle 150 to the cartridge 121 is not limited to the above, and other fixed connections are also possible. Such as screwing, interference fit or welding, etc. Hereinafter, the fixed connection may be any fixed connection commonly used in the art. Of course, the fixed connection may be a detachable fixed connection (e.g., a screw connection) or a non-detachable fixed connection (e.g., an adhesive or welding) unless otherwise specified.

In some embodiments, the discharge end of the storage barrel 121 has a plurality of independent discharge ports, and the proximal end of the inner handle 150 has a plurality of feed ports corresponding to the respective discharge ports, each feed port being in communication with a mixing tube. In other embodiments, the discharge end of the storage barrel 121 has a discharge port communicating with each storage chamber, and the proximal end of the inner handle 150 has a feed port corresponding to the discharge port, the feed port communicating with the mixing tube.

In some embodiments, a sealing boot 130 is also disposed between the inner handle 150 and the storage cartridge 121. The sealing sleeve 130 is used for sealing the gap between the inner handle 150 and the discharge end of the storage cylinder 121 to prevent the material from leaking out from the gap between the material pipe and the storage cylinder 121. Of course, the sealing sleeve 130 has a material hole 131 through which the material passes. Please refer to fig. 4 and 10. In the illustrated embodiment, the sealing sleeve 130 has three material holes 131 corresponding to the discharge ports. It is understood that in other embodiments, the sealing sleeve 130 may have only one material aperture 131. Optionally, the sealing boot 130 is a sealing ring 180. It is understood that in other embodiments, the boot seal 130 may be omitted. When the sealing sleeve 130 is omitted, there is no gap between the inner handle 150 and the discharge end of the cartridge 121 or the gap between the inner handle 150 and the discharge end of the cartridge 121 is small enough that the liquid does not leak. Further, it is understood that in other embodiments, the material assembly may also be omitted. When the material assembly is omitted, the external part for supplying the material is only needed.

Referring to fig. 4, in some embodiments, a mixing core 155 is disposed within the mixing tube. The mixing core 155 is used to mix the materials. By the arrangement of the mixing core 155, the function of spraying the liquid medicine or the material stock solution after mixing in the sprayer 10 can be realized. Optionally, the mixing core 155 is near the proximal end of the mixing tube. So set up, can make the material mix more evenly. In some embodiments, the mixing core 155 includes a core leg and vanes staggered axially along the core leg. In one embodiment, the mixing core 155 is substantially fishbone shaped. Optionally, the mixing core 155 comprises a core stem and a plurality of vanes staggered on the core stem. Optionally, the included angle between the vanes is from 30 ° to 90 °. It is understood that in other embodiments, the shape of the mixing core 155 is not limited to the above, but may be other shapes that facilitate mixing. Of course, in other embodiments, the mixing core 155 may be omitted.

Referring to fig. 11 to 14, in some embodiments, an elastic clip 153 is disposed on an outer side of the mixing tube, and a slot 161 adapted to the elastic clip 153 is disposed in the sleeve; when the elastic clamping piece 153 is clamped in the clamping groove 161, the distal end of the mixing pipe is in sealing connection with the sleeve. The mutual matching of the elastic clamping piece 153 and the clamping groove 161 ensures that the clamping connection between the inner handle 150 and the outer handle 160 is more stable, and the inner handle 150 is prevented from being withdrawn from the air pipe joint 163. Alternatively, the elastic clip 153 includes an elastic handle and a clip point, the clip point is fixedly connected with the elastic handle, and the clip point protrudes to the radial direction of the elastic handle and can be located in the clip slot 161.

Referring to fig. 14, further, a guide groove 162 is formed in the sleeve, and the elastic clip 153 can slide to the slot 161 along the guide groove 162. The installation of the outer handle 160 and the inner handle 150 is facilitated by the provision of the catching groove 161.

In some embodiments, a sealing ring 180 is disposed between the distal end of the mixing tube and the air chamber portion, and the distal end of the mixing tube has a conical head structure 151, and when the elastic clip 153 is clipped in the clipping groove 161, the conical head structure 151 abuts against the sealing ring 180 to seal one end of the air chamber portion. Further, the distal end of the conical head structure 151 has a mounting post 154, and the sealing ring 180 is disposed on the mounting post 154. The provision of mounting post 154 facilitates securing of sealing ring 180. In the illustrated embodiment, the mounting post 154 is hollow and cylindrical. It is understood that in other embodiments, the mounting post 154 is not limited to a hollow cylinder but may be other hollow shapes.

In some embodiments, the inner tube 171 is circular in cross-section. By setting the cross section of the inner tube 171 to be circular, the gas is ensured to be unobstructed. It is understood that, in other embodiments, the shape of the cross section of the inner tube 171 is not particularly limited, and may be other shapes such as an elliptical ring shape, a hollow diamond shape, and the like.

Specifically, the air tube connector 163 is adapted to be connected to a component that provides a source of air (e.g., the external air tube 20 of compressed air).

In some embodiments, a hand grip 152 is provided on the inner handle 150 and/or the outer handle 160. The handle portion 152 facilitates manipulation of the inner handle 150 and the outer handle 160 for ease of installation and removal.

Referring to fig. 16, in some embodiments, the inner tube 171 is a profile tube, and the surface thereof is provided with a supporting bar 173 for supporting the outer tube 172. Optionally, the axial direction of the support bar 173 is the same as the axial direction of the inner tube 171. The support bars 173 have the function of defining the position of the outer tube 172, so that the inner tube 171 and the outer tube 172 are coaxial as much as possible and the airflow in the airflow channel is smooth, thereby preventing the airflow from being unevenly distributed. In the illustrated embodiment, there are three support bars 173. It is understood that the number of the supporting bars 173 is not limited to the above in other embodiments. It is understood that the support bar 173 may be omitted.

Referring to fig. 16, in some embodiments, at the distal end of sprinkler 10, a liquid flow passage extends from the gas flow passage. The liquid flow channel extends out of the gas flow channel, so that compressed gas in the gas flow channel drives the feed liquid in the liquid flow channel to be sprayed out.

Alternatively, referring to fig. 17 to 19, in some embodiments, the sprayer 10 further includes a capillary tube 140 and a flow limiting joint 190, the capillary tube 140 is inserted into the inner tube 171, the liquid flow passage further includes a flow passage portion in the capillary tube 140, the flow limiting joint 190 can be inserted between the outer tube 172 and the capillary tube 140, the capillary tube 140 extends from the flow limiting joint 190, the gas flow passage further includes a flow passage portion of the flow limiting joint 190, and the flow passage portion is gradually narrowed toward a distal direction. In an alternative specific example, the liquid flow passage is formed by the mixture pipe, the inner pipe 171, and the capillary tube 140; the gas flow path is formed by the gas chamber section, the outer tube 172 and the flow restricting fitting 190.

Referring to fig. 18 and 19, in some embodiments, the flow restriction joint 190 is in the form of a hollow cap bolt, and the distal end of the flow restriction joint 190 is hemispherical. Optionally, the inner diameter of the restriction joint 190 tapers in a distal direction. For example, the hollow portion of the restriction 190 may be tapered. It is understood that, in other embodiments, the hollow portion of the flow restricting joint 190 is not limited to the above shape, and may be any other shape with gradually decreasing inner diameter. It will be appreciated that the restriction fitting 190 can, on the one hand, limit the distance that the capillary tube 140 extends beyond the outer tube 172 to ensure that the restriction fitting 190 and the capillary tube 140 form a nozzle structure; on the other hand, the flow rate of the material flowing out of the sprinkler 10 can be increased, which is beneficial to spraying. In some embodiments, the flow restricting fitting 190 is threaded or sealingly snapped into engagement with the inner wall of the outer tube 172.

Alternatively, referring to fig. 20 to 23, in other embodiments, the sprayer 10 further includes a capillary tube 140, the capillary tube 140 is inserted into the inner tube 171 and extends from the outer tube 172, the liquid flow path further includes a flow path portion in the capillary tube 140, and the outer tube 172 is gradually narrowed at a distal end around the capillary tube 140 and forms the gas nozzle 111 in cooperation with the capillary tube 140. In an alternative specific example, the liquid flow passage is formed by the mixture pipe, the inner pipe 171, and the capillary tube 140; the gas flow path is constituted by the gas chamber portion and the outer tube 172.

Specifically, the outer tube 172 has a necked-in portion 175 from which the capillary tube 140 extends, the necked-in portion 175 tapering around the capillary tube 140 and cooperating with the capillary tube 140 to form the gas jet 111. In the illustrated embodiment, the cuff 175 is substantially hemispherical with a hole in the middle. It is understood that in other embodiments, the shape of the cuff 175 is not limited to hemispherical. It can be understood that the closing-in portion 175 can limit the expansion distance of the inner tube 171 (limit the inner tube 171 to move in the direction of the air flow), accelerate the air flow, and form a high-speed air flow to spray the liquid on the wound surface; on the other hand, the length of the closing-in portion 175 is shorter than that of the flow limiting joint 190, and the capillary 140 can be centered automatically under the limiting effect of the inner tube 171, so that the spraying effectiveness is guaranteed.

It will be appreciated that in other embodiments, the capillary 140 may be omitted. When the capillary 140 is omitted, the inner tube 171 has a smaller inner diameter at the distal end than at the proximal end and no stop strip is present.

Of course, in use, the connection between the storage tank 121 and the mixing tube, the connection between the mixing tube and the inner tube 171, the air tube fitting 163 and the supply of compressed gas (e.g., compressed air or compressed CO)₂) The connections between the components of (a) and (b), the connection between the outer tube fitting and the outer tube 172, and the connection between the capillary tube 140 and the inner tube 171 are all connections with good air tightness so as to avoid air leakage or liquid leakage.

In some embodiments, sprayer 10 is a single use product. It will be appreciated that in other embodiments, the sprayer 10 is a reusable product.

In some embodiments, the sprayer 10 described above is used to prepare medical glues. Alternatively, the sprayer 10 described above is used to prepare a medical gel. Specifically, the sprayer is matched with an endoscope for use, and medical glue is sprayed to the focus, so that the medical glue gels at the focus, and the aim of treating the focus is fulfilled.

In some embodiments, the sprayer 10 described above is used with an endoscope. That is, the sprayer 10 is a sprayer for supplying a liquid medicine or a material stock solution under a medical endoscope.

The sprinkler 10 is used in conjunction with a compressed gas controller. Alternatively, the feed liquid spray rate is controlled by controlling the liquid flow rate, and the compressed gas (e.g., air, CO) is controlled₂Etc.) to control the spraying distance and droplet size of the sprayer 10 spraying the feed liquid, thereby stably and accurately conveying the feed liquid to the wound surface and realizing the functions of stable conveying and targeted spraying.

In addition, the application of the medical glue under the digestive endoscope is further provided in an embodiment of the application. Optionally, in some embodiments, the medical gel is delivered to the lesion with the aid of an endodigestive endoscope using the applicator 10 of any of the above embodiments.

In addition, an embodiment of the present application further provides a method for using the medical adhesive, which is used with an endoscope and the sprayer 10 of any of the above embodiments, and the method for using the medical adhesive includes steps S10, S20, S30 and S40.

Step S10: the stock solution of the medical adhesive is filled into the storage cylinder 121.

Step S20: the inner handle 150 is mounted to the cartridge 121 and the external air tube 20 is connected to a source of compressed air.

Step S30: the storage cylinder 121 is clamped into a medical micro-injection pump and is adjusted to a certain injection speed, and the compressed air source is also adjusted to a certain pressure.

Step S40: push-injecting and compressed air button is started, and the stock solution of the medical glue is sprayed to the focus of digestive tract mucosa.

In one embodiment, sprinkler 10 has three separate reservoirs. The step of filling the stock solution of the medical adhesive into the storage cylinder 121 includes: and respectively filling the reagent A, the reagent B and the reagent C into three independent storage cavities.

In some embodiments, pulling the inner handle 150 proximally ensures that the capillary tube 140 is retracted within the outer tube 172 or the flow restricting fitting 190 and the double cannula 170 is passed through the endoscope to the lesion site. The inner handle 150 is pushed towards the far end, the capillary 140 extends out from the outer tube 172 or the flow limiting joint 190 to form a nozzle, and meanwhile, the conical head structure 151 and the outer handle 160 at the far end of the inner handle 150 are tightly attached to the sealing ring 180 to seal one end of the air cavity part. Following the above-described operation, double cannula 170 requires that inner handle 150 be pulled back before it can be passed through the endoscope, ensuring that capillary 140 is retracted from outer tube 172 or restricted flow fitting 190; when the lesion position is reached, the inner handle 150 is pushed forward, the capillary 140 extends out from the outer tube 172 or the flow limiting joint 190 to form a nozzle, and meanwhile, the distal end conical head structure 151 of the inner handle 150, the outer handle 160 and the sealing ring 180 are tightly attached to form an air flow channel, so that external air flow can smoothly reach the nozzle. By arranging for the hair cells 140 to retract into the outer tube 172 or the flow restricting fitting 190 before reaching the lesion and extend out of the outer tube 172 or the flow restricting fitting 190 after reaching the lesion, the capillary 140 is protected such that the capillary 140 is not easily damaged before reaching the lesion.

In some embodiments, the inner handle 150 is first connected to the inner tube 171, the outer handle 160 is connected to the outer tube 172, and then the inner tube 171 is passed through the outer handle 160 and into the outer tube 172 to form the double cannula 170, the inner handle 150 is snapped into the outer handle 160, and the cone structure 151 seals one end of the air chamber portion against the sealing ring 180. It is understood that in other embodiments, the order of attachment of the cartridge 121, the inner handle 150, the outer handle 160, and the double cannula 170 is not limited to the above, but may be other. In one embodiment, the step of coupling the inner handle 150 to the outer handle 160 comprises: the inner handle 150 is pushed into the outer handle 160 under the guidance of the guide groove 162, the elastic clamping piece 153 is clamped in the clamping groove 161, and the distal end of the mixing tube presses the sealing ring 180 to seal one end of the air chamber part, so that the tightness of the inner handle 150 and the outer handle 160 is ensured. Optionally, the compressed air source is medical compressed air.

It will be appreciated that the material stock and air flow rates for the medical gel may be adjusted according to the properties of the medical gel.

Certainly, the raw material liquid of the medical adhesive in the storage cylinder 121 is in an uncured state, and after the raw material liquid of the uncured medical adhesive flows out of the storage cylinder 121, the raw material liquid of the uncured medical adhesive is conveyed through the mixing tube and the inner tube 171 of the double-sleeve 170 and sprayed to the focus of the digestive tract mucosa, and after the raw material liquid of the uncured medical adhesive is sprayed, the raw material liquid of the uncured medical adhesive is cured in situ to cover, bond and close the focus, so that the effects of preventing bleeding and perforation and promoting the healing of the focus of the mucosa are achieved.

It is understood that the sprayer is not limited to the sprayer 10, but may be other sprayers.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The following detailed description is given with reference to specific examples. The following examples are not specifically described, and other components except inevitable impurities are not included. Reagents and instruments used in the examples are all conventional in the art and are not specifically described. The experimental procedures, in which specific conditions are not indicated in the examples, were carried out according to conventional conditions, such as those described in the literature, in books, or as recommended by the manufacturer. Herein, "wt%" means mass percent concentration.

Example 1

The main compositions for preparing the gels of this example are shown in table 1, and the method for preparing the gels of this example includes, but is not limited to, the following steps:

(1) preparation of binding polymer: 1) melting reaction: adding 3.72g of citric acid, 6.34g of polyethylene glycol (weight average molecular weight of 400Da), 3.52g of four-arm polyethylene glycol (weight average molecular weight of 2000Da) and 1.00g of dopamine hydrochloride into a three-neck flask at the same time, charging nitrogen for 15min, placing the three-neck flask into an oil bath kettle heated to 160 ℃, starting stirring, melting for 2h while stirring, adding an acid catalyst after reactants are completely melted, continuously stirring for reaction until the reaction is finished, stopping stirring and heating, and stopping charging nitrogen to obtain a crude product. 2) Dissolving: 30g of purified water was poured into the three-necked flask after the reaction in step (1), and stirring was turned on for 24 hours to dissolve the crude product. 3) And (3) dialysis: dispersing the dissolved crude product obtained in step 2) in purified water, and dialyzing with dialysis bag with molecular weight cutoff of 3000 continuously for 20 times, each time for 3 h. 4) Freeze-drying: and (3) pouring the product after dialysis in the step 3) into a plastic dish, pre-freezing for 24 hours at the temperature of minus 10 ℃, and then freeze-drying to obtain a colloidal product, thus obtaining the adhesive polymer.

(2) According to the table 1, a certain amount of chitosan and four-arm PEG-400 are dissolved in a certain amount of purified water together to obtain a mixed solution, and the pH value of the mixed solution is adjusted to 3.5 by hydrochloric acid to prepare a reagent A, wherein the concentration of the chitosan in the reagent A is 0.1 wt%, and the concentration of the four-arm PEG-400 is 2 wt%. Diluting a certain amount of glyoxal solution with a certain concentration in a certain amount of purified water, and adjusting the pH value of the mixed solution to 3.5 by using hydrochloric acid to ensure that the concentration of the glyoxal is 1.5 wt%, thereby preparing a reagent B. Dissolving a certain amount of bovine serum albumin, propane diamine, the bonding polymer prepared in the step (1) and methylene blue in a certain amount of purified water, and adjusting the pH value of the solution to 7.5 by using sodium hydroxide to prepare a reagent C, wherein in the reagent C, the concentration of the bovine serum albumin is 0.5 wt%, the concentration of the propane diamine is 0.05 wt%, the concentration of the bonding polymer is 2 wt%, and the concentration of the methylene blue is 0.0001 wt%.

(3) According to the mass ratio of 5: 1: 1A reagent, B reagent and C reagent were stirred in a vessel with a glass rod to prepare a gel of this example.

Examples 2 to 16

The main compositions of the gels of preparation examples 2 to 16 are specifically shown in table 1. The method of preparing the gels of examples 2 to 16 is substantially the same as example 1, and differs only in the main composition, and referring specifically to table 1, the operations of the respective examples are adjusted adaptively according to the composition. In examples 2 to 16, the adhesive polymer of example 5 was different from the adhesive polymer of example 1 in that the adhesive polymer of example 5 was prepared in such a manner that the mass of citric acid was 3.72g, the mass of polyethylene glycol (weight-average molecular weight 400Da) was 6.69g, the mass of four-arm polyethylene glycol (weight-average molecular weight 2000Da) was 1.76g, and the mass of dopamine hydrochloride was 1.00 g.

Performance testing

1. The medical adhesive lap joint-shear bonding strength test method comprises the following steps:

the test method is as follows: the lap-shear bond strength was tested by using a polymer substrate (fiberboard) having a size of 100mm × 25mm (length × width), applying the gel of example to the end (10mm × 25mm area) of the substrate, superimposing another end (10mm × 25mm area) of the same size of the substrate to the above-described end of the substrate, curing at 37 ℃ for 1 hour, followed by standing at room temperature for 120min (ref: YY/T0729.1-2009, part 1). The test results are shown in Table 1.

2. The acid-resistant enzyme degradation period test method in the artificial gastric juice comprises the following steps:

the gels of each example were immersed in a lidded container containing an artificial gastric juice at a ratio of 1g/20mL, and then placed in a shaker at 37 ℃ and 50 rpm. The acid-resistant enzyme degradation cycle (occurrence of global degradation shedding) of each gel was observed with time, and the results are shown in Table 1.

As can be seen from Table 1, when the reagent A comprises a water-soluble polyhydroxy polymer with a concentration of 0.005 wt% -10 wt%, the reagent B comprises an aldehyde compound with a concentration of 0.001 wt% -8 wt%, the reagent C comprises a water-soluble protein with a concentration of 0.001 wt% -40 wt%, the pH of the reagent A is 0.01-7, the pH of the reagent B is 0.01-10, and the pH of the reagent C is 0.01-10, the prepared gel has an adhesive strength of 27.2 +/-7.5 kPa-1109.0 +/-190.8 kPa, a degradation period of 3-31 days, and the gel has high adhesive strength and is not easily degraded by gastric juice.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, so as to understand the technical solutions of the present invention specifically and in detail, but not to be understood as the limitation of the protection scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. It should be understood that the technical solutions obtained by logical analysis, reasoning or limited experiments based on the technical solutions provided by the present invention are all within the protection scope of the appended claims of the present invention. Therefore, the protection scope of the present invention should be subject to the content of the appended claims, and the description and the drawings can be used for explaining the content of the claims.

Claims

1. The medical adhesive is characterized in that a material stock solution used by the medical adhesive comprises a reagent A, a reagent B and a reagent C, wherein the reagent A comprises a water-soluble polyhydroxy polymer with the concentration of 0.005-10 wt%, the reagent B comprises an aldehyde compound with the concentration of 0.001-8 wt%, the reagent C comprises a water-soluble protein with the concentration of 0.001-40 wt%, the sum of the concentration of the water-soluble polyhydroxy polymer and the concentration of the water-soluble protein is not less than 0.08 wt%, the pH of the reagent A is 0.01-7, the pH of the reagent B is 0.01-10, and the pH of the reagent C is 0.01-10.

2. The medical glue of claim 1, wherein the medical glue has a bond strength of 20kPa to 1300 kPa.

3. The medical glue of claim 1, wherein the acid-resistant enzymatic degradation cycle of the medical glue is between 3 days and 31 days.

4. The medical gel as claimed in claim 1, wherein the water-soluble protein is at least one selected from the group consisting of serum albumin, ovalbumin, serum globulin, concanavalin a, water-soluble glycoprotein and collagen;

5. The medical glue of any one of claims 1 to 4, wherein the reagent A further comprises at least one of polyethylene glycol, a polyethylene glycol derivative, an antibacterial agent and a water-soluble inorganic salt; the sum of the concentration of the polyethylene glycol and the concentration of the polyethylene glycol derivative is 0.001 wt% -10 wt%; the concentration of the antibacterial agent is 0.00001 wt% -2 wt%; the concentration of the water-soluble inorganic salt is 0.001-5 wt%;

6. The medical glue of claim 5, wherein the diamine is at least one selected from the group consisting of ethylenediamine, propylenediamine, and butylenediamine;

and/or the pigment is brilliant blue, methylene blue or indigo carmine.

7. The medical glue according to any one of claims 1 to 4 and 6, characterized in that the ratio of the mass of the agent A, the agent B and the agent C is (1 to 5): 1: (1-5).

8. The medical glue according to claim 7, characterized in that it is a gel for peptic ulcers or wounds.

9. The method for preparing the medical adhesive according to any one of claims 1 to 8, which is characterized by comprising the following steps: and mixing the reagent A, the reagent B and the reagent C to prepare the medical adhesive.

10. The method for preparing medical adhesive according to claim 9, wherein the agent a, the agent B and the agent C are mixed under a gastroenterological endoscope by using a sprayer, the sprayer comprising a storage barrel, an inner handle, an outer handle and a double cannula;

the proximal end of the outer tube of the double-cannula can be connected with the outer tube joint, and the proximal end of the inner tube of the double-cannula can be connected with the distal end of the inner handle;

the sprayer is provided with a liquid flow passage and a gas flow passage, the liquid flow passage comprises a flow passage part formed by matching the mixing pipe and the inner pipe, the gas flow passage comprises a flow passage part formed by matching the outer pipe and the gas cavity, and the liquid flow passage and the gas flow passage are narrowed at the far end;