CN112138202A - Temperature sensitive digestive tract mucosa protective adhesive - Google Patents
Temperature sensitive digestive tract mucosa protective adhesive Download PDFInfo
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- CN112138202A CN112138202A CN201910496774.0A CN201910496774A CN112138202A CN 112138202 A CN112138202 A CN 112138202A CN 201910496774 A CN201910496774 A CN 201910496774A CN 112138202 A CN112138202 A CN 112138202A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/043—Mixtures of macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
Abstract
The invention relates to a temperature-sensitive mucosa protective gel for digestive tract injury, belonging to the field of biological pharmaceutical preparations. The mucosa protective gel for digestive tract injury comprises a temperature sensitive biomaterial, a gelation temperature regulator, a biological adhesive and a dissolving solution. Temperature sensitive biological material, gelation temperature regulator and biological adhesive, the weight percentage of which is 1-30: 0.5-5: 0.3-5. Under the action of the temperature lower than room temperature (25 ℃), the protective gel is liquid and forms a colloidal membrane at the body temperature (37 ℃), thereby avoiding the stimulation effect of intestinal digestive juice on digestive tract injured mucosa and promoting the healing of wound surfaces. Animal experiments show that the invention can obviously promote the repair of injured mucosa, thereby having the functions of promoting healing and protecting the injury of esophagus, stomach and intestinal mucosa.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a temperature-sensitive digestive tract mucosa protective adhesive suitable for being sprayed on the surface of a digestive tract injured mucosa by an endoscope.
Background
Lesions of the digestive mucosa can occur from the esophagus, stomach, duodenum to rectum, some lesions are caused by disease and some are caused by surgery. The endoscopic gastric mucosa resection and gastric mucosa stripping are minimally invasive surgeries for resection of early gastric cancer and gastric benign tumors, can achieve the aim of radically treating the early gastric cancer, have the advantages of small wound, small influence on the life quality of patients and the like, and gradually replace part of the traditional surgical operations. Minimally invasive surgery for early cancerous and benign tumor removal of the esophagus and colon also replaces part of traditional surgery. However, at present, the mucosa wound caused by the operation is only treated with hemostasis treatment, and no good wound protection measures are available. The bare mucosa wound surface is subjected to ulcer activity, healing and scar stages under the action of digestive juice, and the healing time of the wound surface is longer. Clinical research data show that the healing rate of patients after 6 weeks of endoscopic gastric mucosal resection and gastric mucosal dissection is about 69%. Therefore, there is a need for a product that can be applied directly endoscopically to the mucosal surface of the injured digestive tract.
Although attempts to cover the gastric ulcer wound surface under a gastroscope by using astragalus bletilla striata gum (natural polysaccharide component extracted from traditional Chinese medicines) and alpha cyanoacrylate adhesives were made as early as 1994, the popularization and application of the technology are limited due to the shortage of the materials. Researchers who used the treated human fresh amniotic allogenic material to study a gastric injury model of an animal dog in 2017 prove that the wound surface which is not covered is observed to be endothelialized after the wound surface is covered on the gastric injury mucosa by adopting fresh amniotic suture for 21 days, while most of the wound surface which is covered by the fresh amniotic membrane is covered by the new endothelial cells, and the gastric injury mucosa covering biomaterial is proved to be capable of remarkably promoting the reconstruction and endothelialization of the injury mucosa. With the development of repair materials, it is typical that Takimoto reports that the wound surface is covered by a PGA film at the parts of pig stomach, duodenum and the like, fibrin glue is applied to combine with the PGA film, or a hemostatic clamp is used to combine with the PGA film, so that the film can be prevented from slipping. The PGA film is covered to avoid the contact of digestive juice and the wound surface, and keep the wound surface clean, especially the large wound surface of the stomach. The repair material PGA can guide cells to creep and promote wound healing. The PGA combined with the bioprotein adhesive is used for treating the wound surface after the ESD operation, the risk of perforation of duodenum after the ESD operation can be reduced, and the PGA membrane is applied to the huge wound surfaces of esophagus, duodenum and the like, so that the stenosis of the digestive tract after the operation caused by scars can be effectively prevented. Spiliopoulos et al reported that horse heart envelope was used as a patch for full-thickness perforation of rabbit stomach wall, the experiment was performed laparoscopically, and gastric pressure was measured at 3d, 1 week, and 2 weeks after surgery in parallel with pathological and immunohistochemical examinations, and the results showed that the wound surface healed faster, the repair had very strong pressure resistance, and pathological and immunohistochemical examinations showed that inflammatory cells, granulation tissue, and growth factors were all much or higher than those in the control group. Although the curative effect of the novel repair material is confirmed, most of the material is cut into strips and is delivered to the wound part through a biopsy hole, and particularly for large wounds, the complete material laying has a good protection effect on the wounds. However, the difficulty in fixing these materials on the wound surface limits the clinical use of these materials. In 2016, 26 patients with upper gastrointestinal early cancer who receive ESD treatment are selected as research objects in China, and the research objects are randomly divided into a cover membrane group and a control group according to whether the wound surface is covered with a polyglycolic acid (PGA) membrane. And analyzing the occurrence condition of postoperative complications, the wound healing degree, the liver and kidney functions and the change of blood routine between the two groups, and comparing the attaching conditions of different fixing modes to the PGA film and the wound. As a result, no complications occurred after the operation in both the control group and the film-covered group. The healing rate of the wound surface after 1 month of the tectorial membrane module operation is obviously better than that of a control group (P is less than 0.05). Domestic and foreign researches show that the wound surface of the alimentary canal mucosa can be obviously promoted to heal by covering the surface with biomedical materials. At present, no similar products are clinically applied at home and abroad, and the product of the temperature-sensitive digestive tract injury mucosa protective gel is only in the stage of preclinical animal test research at home and abroad, does not need sewing and is more convenient to use, and belongs to an innovative product of medical equipment with international originality.
Disclosure of Invention
Aiming at the defects in the technical field, the invention provides a brand-new method and a product for protecting the mucosa of the digestive tract by adopting a physical principle, the temperature-sensitive protective glue for the mucosa of the digestive tract injury can be completely dissolved into a liquid state in water at the temperature lower than room temperature (25 ℃), can be conveniently sprayed to the surface of the injured mucosa by an endoscope, forms a solid gel film under the condition of body temperature (37 ℃), avoids the stimulation and the digestion of digestive tract digestive.
The temperature sensitive digestive tract injury mucosa protective gel comprises temperature sensitive biological material, gelation temperature regulator and biological adhesive. Wherein the weight percentage of the temperature sensitive biomaterial, the gelation temperature regulator and the biological adhesive is 1-30: 0.5-5: 0.3-5.
Further, the components of the protective gel are dissolved in the dissolving solution to form an isotonic solution.
The temperature-sensitive biomaterial is one or more of poly-N-isopropylacrylamide and derivatives thereof, hydroxybutyl chitosan and derivatives thereof, poloxamer 407(P407), polylactic acid/glycolic acid/polyethylene glycol copolymer, polyethylene glycol monomethyl ether- (sebacic acid-D, L-lactic acid) polyester anhydride-polyethylene glycol monomethyl ether triblock copolymer, cellulose and derivatives thereof and polyethylene glycol/polycaprolactone block copolymer.
The gelation temperature regulator is one or more of poloxamer 188(P188), polysorbate, and polyethylene glycol.
The phase transition temperature of the protective adhesive is 25-40 ℃.
The biological adhesive is carboxymethyl cellulose, sodium alginate, carboxymethyl chitosan, carbomer, ethyl cellulose, hydroxypropyl methyl cellulose, bletilla polysaccharide, polylysine, mussel adhesive protein, collagen, polydopamine, sodium hyaluronate and chitosan quaternary ammonium salt.
The dissolving solution is physiological saline and phosphate solution.
Further, in one embodiment, the protective gel comprises poloxamer 407, poloxamer 188, hydroxypropyl methylcellulose, poloxamer 407: poloxamer 188: the weight ratio of the hydroxypropyl methyl cellulose is 17:1:1, and the dissolving agent is physiological saline.
The temperature-sensitive digestive tract injury mucosa protective gel also comprises one or more pharmaceutical compounds or compositions for treating ulcer and tumor.
The invention also provides application of the temperature-sensitive digestive tract injury mucosa protective gel in preparing medicines for treating wound surfaces after peptic ulcer, digestive tract mucosa injury ulcer, stress ulcer, ulcerative colitis, gastric mucosa resection and dissection, esophageal mucosa dissection and intestinal mucosa dissection.
Compared with the prior art, the invention has the following advantages:
the temperature-sensitive alimentary canal mucosa protective gel comprises a temperature-sensitive material, a gelation temperature regulator and a biological adhesive, wherein the temperature-sensitive material is liquid at a temperature lower than room temperature (25 ℃), and the temperature-sensitive material is subjected to phase change at body temperature (37 ℃), so that the temperature-sensitive material is changed into a gel film from liquid through phase change, and the adhesive provides a property of being bonded to damaged mucosa, so that the gel film is attached to the mucosa and is not easy to fall off, the digestive effect of digestive juice on the mucosa is blocked, and the effects of protecting the damaged mucosa and promoting wound healing are achieved.
Detailed Description
The present invention will be described in further detail with reference to examples.
Example 1
1. Poloxamer 40717 g
2. Poloxamer 1881 g
3. Hydroxypropyl methylcellulose 1 g
________________________________________________________________
The above components are dissolved in 60ml of normal saline at 4 ℃ to form transparent liquid after being completely dissolved, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the high-temperature steam sterilization is carried out. And (5) low-temperature preservation.
Example 2
1. Poloxamer 40730 g
2. Poloxamer 1882 g
3. Hydroxypropyl methylcellulose 1 g
_________________________________________________________________
The above components are dissolved in 60ml of normal saline at 4 ℃ to form transparent liquid after being completely dissolved, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the high-temperature steam sterilization is carried out. And (5) low-temperature preservation.
Example 3
1. 5 g of hydroxybutyl chitosan
2. Poloxamer 1880.5 g
3. Polylysine 2 g
_________________________________________________________________
The above components are dissolved in 60ml of normal saline at 4 ℃ to form transparent liquid after being completely dissolved, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the high-temperature steam sterilization is carried out. And (5) low-temperature preservation.
Example 4
1. Hydroxybutyl chitosan 8 g
2. Poloxamer 1880.5 g
3. Polylysine 2 g
_________________________________________________________________
The above components are dissolved in 60ml of normal saline at 4 ℃ to form transparent liquid after being completely dissolved, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the high-temperature steam sterilization is carried out. And (5) low-temperature preservation.
Example 5
1. Poly (N-isopropylacrylamide) 10 g
2. Poloxamer 1880.5 g
3. Polylysine 2 g
_________________________________________________________________
The above components are dissolved in 60ml of isotonic phosphate solution at 4 ℃, the solution is completely dissolved to form transparent liquid, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the bottle is sterilized by high-temperature steam. And (5) low-temperature preservation.
Example 6
1. Poloxamer 40717 g
2. Poloxamer 1881 g
3. Hydroxypropyl methylcellulose 1 g
_________________________________________________________________
The above components are dissolved in 60ml of normal saline at 4 ℃ to form transparent liquid after being completely dissolved, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the high-temperature steam sterilization is carried out. And (5) low-temperature preservation.
Example 7
1. Poloxamer 40717 g
2. Poloxamer 1881 g
3. Hydroxypropyl methylcellulose 1 g
_________________________________________________________________
The above components are dissolved in 60ml of isotonic phosphate buffer solution at 4 ℃, the solution is completely transparent liquid, then the volume is determined to be 100ml, each bottle is packed with 5ml, and the solution is sterilized by high-temperature steam. And (5) low-temperature preservation.
Experimental examples evaluation of Effect
The above liquids were used directly in the experiments.
1 test example
In vitro colloidal film formation test
2ml of the liquid is respectively taken and coated on the inner side surface of fresh pigskin which is preheated to 37 ℃, then the pigskin is placed in a thermostat at 37 ℃ for 3 minutes, and the formation of a colloid membrane is observed. As a result, a colloidal film was formed in each of examples 1 to 7.
2 test example 2
Safety research test
Examples 1-7 were subjected to the following biological tests
1) Stimulation of oral mucosa: 12ml of the colloidal solution was poured into a sterile petri dish having a diameter of 15cm, and then placed in a 37 ℃ incubator for 3 minutes to form a film, and then a physiological saline was added at a ratio of 3cm2/ml, and the solution was extracted at 37 ℃ for 72 hours to prepare a test solution. The experimental liquid of the sample is made into a cotton ball with the diameter not more than 5mm and soaked in the cheek capsule on one side of 3 golden yellow mice. The contact time is minimum 5min each time, once a day, 4 times totally, after the last contact, the cheek sacs are observed visually 24h, the mice are killed painlessly, tissue samples of representative parts of the cheek sacs are taken and put into 4% formaldehyde solution for fixation, and histological evaluation is carried out after tissue sections are made. The stimulation indexes are all 0, and the tested sample has no oral mucosa irritation.
2) Cytotoxicity: 12ml of the colloidal solution was poured into a sterile petri dish having a diameter of 15cm, and then placed in a 37 ℃ incubator for 3 minutes to form a film, and then the test solution was prepared by adding a culture medium at a ratio of 3cm2/ml and leaching at 37 ℃ for 24 hours. Then, the cytotoxicity is measured by MTT method according to the cytotoxicity test specified in GB/T16886.5, and the cytotoxicity is in the range of 0-1 grade.
3) Sensitization test: 12ml of the colloidal solution was poured into a sterile petri dish having a diameter of 15cm, and then placed in a 37 ℃ incubator for 3 minutes to form a film, and then a physiological saline was added at a ratio of 3cm2/ml, and the solution was extracted at 37 ℃ for 72 hours to prepare a test solution. Then, no sensitization was observed in any of the skin sensitization tests as specified in GB/T16886.10.
3 test example 3
Measurement of tissue adhesion (tissue retention method):
examples 1 to 7 were each subjected to the following tests
SD rats are taken and fasted for 24h, are anesthetized by intraperitoneal injection with a sodium pentobarbital solution (40mg/kg), the stomach is dissected and taken out, the stomach is cut out in physiological saline (37 ℃), the inner wall of the stomach is cleaned by the physiological saline, and the cleaned stomach is used within 2 h. Cutting a certain area of stomach tissue (2cm multiplied by 2cm), fixing on a polyethylene film, and uniformly coating 0.5ml of protective gel on the stomach mucosa wound surface preheated to 37 ℃. The stomach tissue is placed in a constant humidity closed container with the relative humidity of 92.5 percent for 20 minutes, the treated stomach tissue is fixed on a flushing chute, the angle of the chute is adjusted to 60 ℃, the flow rate of a peristaltic pump is adjusted to 20ml/min, the stomach tissue is flushed with 0.1mol/L hydrochloric acid for 5mins, the flushing liquid is collected in a beaker with a known weight, dried at 70 ℃, weighed, and the tissue adhesion is expressed by the adhesion percentage.
The calculation method is as follows:
percentage of gastric tissue adhesion (Bg/%) Bg/% { [ M- (G-M) ]/M } x 100%
Wherein M is the weight of the mucosa protective glue (0.5ml is dried under the same condition); g is the weight of the empty beaker; g is the total weight of the beaker and the dried residue; m is the amount of solid material contained in the same volume of wash solution (blank control). A larger B value indicates a larger adhesion.
The results show that: example 1: 92%, example 2: 90%, example 3: 91%, example 4: 93%, example 5: 91%, example 6: 92%, example 7: 92 percent. Tests show that the temperature-sensitive mucosa protective glue of the examples 1 to 7 has strong adhesion to tissues and is not easy to fall off.
4 test example 4
Examples 1 to 7 were each subjected to the following animal tests
Animals were divided into two groups, weighing about 3 kg. The experimental group had 6 animals, and the control group had 6 animals.
Fasting is performed 24 hours before operation, and water is not forbidden.
The anesthesia method comprises the following steps: the rabbit is recommended to be injected with 1.0ml/kg of sodium pentobarbital with the mass concentration of 30 g/L.
The rabbit was fixed on the back on the operating table and the abdomen was dehaired. The test area was disinfected with 2% iodine tincture and 75% ethanol solution as required for routine surgical procedures.
The skin, muscle layer and peritoneum are cut layer by layer in the upper abdomen, and if bleeding is caused, ligation is carried out to stop bleeding. Exposing the stomach, stimulating the stomach at the greater curvature of the stomach, washing the stomach with normal saline, injecting 1:10000 epinephrine normal saline under the mucosa on the lateral surface of the greater curvature of the stomach, injecting 1ml of normal saline to form gastric mucosa protrusion, then using a loop device to cut the mucosa with the diameter of 1cm to form a wound surface, spraying thrombin (1ml containing 50U of thrombin) and completely stopping bleeding by compression, and measuring the diameter of the wound surface. The control group was not treated, and the experimental group was coated with 0.5ml of protective gel and then the stomach was sutured. Then the abdominal wall is sutured layer by layer. Placing in a feeding cage, and fasting for one day.
And (4) observing results: the animals are euthanized 1 week after the operation, the stomach wall is cut along the original incision, the healing condition of the wound surface is observed, the diameter of the wound surface is measured, and the result shows that 5 rabbits in the experimental group with the ulcer 1 week after the operation in the experimental group in the example 1 are healed, 1 rabbit is not healed, and the healing rate is 83%; the control group had 2 healed, 4 not healed, and the healing rate was 33%. The results show that the protective gel of the embodiment 1 can obviously promote the healing of the gastric mucosa injury ulcer and has obvious therapeutic effect on the gastric ulcer.
The above experiments were repeated with the protective gels of examples 2-7, and the healing rates of the experimental groups were significantly higher than those of the control group. It can be seen that the protective gel of examples 2-7 can also significantly promote the healing of the ulcer due to gastric mucosa injury, and has significant therapeutic effect on gastric ulcer.
The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit of the invention.
Claims (10)
1. The temperature-sensitive digestive tract injury mucosa protective gel is characterized in that the protective gel comprises temperature-sensitive biological materials, a gelation temperature regulator and a biological adhesive, wherein the weight percentage of the temperature-sensitive biological materials, the gelation temperature regulator and the biological adhesive is 1-30: 0.5-5: 0.3-5.
2. The protective gel for mucosa of digestive tract injury sensitive to temperature according to claim 1, wherein the components of the protective gel are dissolved in a dissolving solution to form an isotonic solution.
3. The temperature-sensitive mucosa protective gel for digestive tract injury according to claim 1, wherein the temperature-sensitive biomaterial is one or more of poly-N-isopropylacrylamide and derivatives thereof, hydroxybutyl chitosan and derivatives thereof, poloxamer 407, polylactic acid/glycolic acid/polyethylene glycol copolymer, polyethylene glycol monomethyl ether- (sebacic acid-D, L-lactic acid) polyester anhydride-polyethylene glycol monomethyl ether triblock copolymer, cellulose and derivatives thereof, and polyethylene glycol/polycaprolactone block copolymer.
4. The temperature-sensitive mucosa protection gel for digestive tract injury according to claim 1, wherein the gelation temperature regulator is one or more of poloxamer 188, polysorbate, and polyethylene glycol.
5. The temperature-sensitive mucosa protective gel for digestive tract injury according to claim 1, wherein the bioadhesive is one or more of carboxymethyl cellulose, sodium alginate, carboxymethyl chitosan, carbomer, ethyl cellulose, hydroxypropyl methyl cellulose, bletilla striata polysaccharide, polylysine, mussel adhesive protein, collagen, polydopamine, sodium hyaluronate, and chitosan quaternary ammonium salt.
6. The temperature-sensitive mucosa protective gel for digestive tract injury according to claim 2, wherein the dissolving solution is one of physiological saline and phosphate solution.
7. The temperature-sensitive mucosa protective gel for digestive tract injury according to claim 1, wherein the protective gel has a phase transition temperature of 25-40 ℃.
8. The temperature-sensitive mucosa protective gel for digestive tract injury according to claim 1, wherein the protective gel comprises poloxamer 407, poloxamer 188, hydroxypropyl methylcellulose, poloxamer 407: poloxamer 188: the weight ratio of the hydroxypropyl methyl cellulose is 17:1:1, and the dissolving agent is physiological saline.
9. The temperature-sensitive mucosa protective gel for digestive tract injury according to any one of claims 1-8, wherein the protective gel further comprises a pharmaceutical compound for treating one or both of ulcer and tumor.
10. Use of a temperature-sensitive mucosa protective gel for digestive tract injury according to any one of claims 1-8 in the manufacture of a medicament for the treatment of wounds following peptic ulcer, digestive tract mucosa injury ulcer, stress ulcer, ulcerative colitis, gastric mucosa resection and dissection, esophageal mucosa dissection and intestinal mucosa dissection.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910496774.0A CN112138202A (en) | 2019-06-10 | 2019-06-10 | Temperature sensitive digestive tract mucosa protective adhesive |
| KR1020217029900A KR20210131375A (en) | 2019-03-12 | 2020-03-11 | digestive tract mucosal protective gel |
| JP2021554415A JP7325853B2 (en) | 2019-03-12 | 2020-03-11 | Protective adhesive for gastrointestinal mucosa |
| PCT/CN2020/078733 WO2020182139A1 (en) | 2019-03-12 | 2020-03-11 | Protective gel for gastrointestinal mucosa |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910496774.0A CN112138202A (en) | 2019-06-10 | 2019-06-10 | Temperature sensitive digestive tract mucosa protective adhesive |
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| CN112138202A true CN112138202A (en) | 2020-12-29 |
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| CN201910496774.0A Pending CN112138202A (en) | 2019-03-12 | 2019-06-10 | Temperature sensitive digestive tract mucosa protective adhesive |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114129767A (en) * | 2021-09-09 | 2022-03-04 | 戴钲昊 | Surface-closed soft tissue wound surface protection glue and application thereof |
Citations (8)
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