WO2021147634A1 - 乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用 - Google Patents
乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用 Download PDFInfo
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- WO2021147634A1 WO2021147634A1 PCT/CN2020/141351 CN2020141351W WO2021147634A1 WO 2021147634 A1 WO2021147634 A1 WO 2021147634A1 CN 2020141351 W CN2020141351 W CN 2020141351W WO 2021147634 A1 WO2021147634 A1 WO 2021147634A1
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- Prior art keywords
- connective tissue
- acetylcysteine
- preparation
- ester
- acceptable salt
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- 210000002808 connective tissue Anatomy 0.000 title claims abstract description 87
- 238000000926 separation method Methods 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 title claims abstract description 49
- 229960004308 acetylcysteine Drugs 0.000 title claims abstract description 48
- 150000002148 esters Chemical class 0.000 title claims abstract description 22
- 150000003839 salts Chemical class 0.000 title claims abstract description 22
- 238000002347 injection Methods 0.000 claims description 23
- 239000007924 injection Substances 0.000 claims description 23
- 239000000243 solution Substances 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 239000000945 filler Substances 0.000 claims description 11
- 239000000499 gel Substances 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 abstract description 24
- 230000000740 bleeding effect Effects 0.000 abstract description 24
- 238000000034 method Methods 0.000 abstract description 19
- 230000008569 process Effects 0.000 abstract description 15
- 238000002224 dissection Methods 0.000 abstract description 7
- 208000034158 bleeding Diseases 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 56
- 206010052428 Wound Diseases 0.000 description 22
- 208000027418 Wounds and injury Diseases 0.000 description 22
- 238000001356 surgical procedure Methods 0.000 description 22
- 230000023597 hemostasis Effects 0.000 description 21
- 210000004877 mucosa Anatomy 0.000 description 20
- 239000000523 sample Substances 0.000 description 19
- 238000012323 Endoscopic submucosal dissection Methods 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 238000010171 animal model Methods 0.000 description 18
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 17
- 241000282887 Suidae Species 0.000 description 15
- 210000000232 gallbladder Anatomy 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 210000000496 pancreas Anatomy 0.000 description 10
- 210000002784 stomach Anatomy 0.000 description 10
- 210000004876 tela submucosa Anatomy 0.000 description 10
- 210000001035 gastrointestinal tract Anatomy 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 230000003111 delayed effect Effects 0.000 description 7
- 238000009297 electrocoagulation Methods 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 230000029663 wound healing Effects 0.000 description 7
- 206010071229 Procedural haemorrhage Diseases 0.000 description 6
- 238000005345 coagulation Methods 0.000 description 6
- 230000015271 coagulation Effects 0.000 description 6
- 239000013068 control sample Substances 0.000 description 6
- 210000003238 esophagus Anatomy 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 230000002439 hemostatic effect Effects 0.000 description 6
- 238000007689 inspection Methods 0.000 description 6
- 210000000936 intestine Anatomy 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 230000002357 endometrial effect Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 235000021056 liquid food Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000002271 resection Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 2
- 210000004177 elastic tissue Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 210000001365 lymphatic vessel Anatomy 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 238000002674 endoscopic surgery Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
Definitions
- the present invention relates to the field of medical preparations, in particular to the application of acetylcysteine or its chemically acceptable salts/esters in the preparation of connective tissue separation preparations.
- Connective tissue is a soft and elastic tissue in the human body. It fills between tissues and organs and is a natural gap between tissues and organs. This connective tissue is widely distributed in the body, and its main function is to support, connect, nourish, defend, protect and repair wounds. These gaps are particularly important for surgical operations, especially for minimally invasive surgery, because the operations in these gaps have clear levels and are ideal locations for separating tissues or organs.
- the present invention provides an application of acetylcysteine or its chemically acceptable salt/ester in the preparation of connective tissue separation preparations.
- the connective tissue separation preparation prepared by acetylcysteine or its chemically acceptable salt/ester can simplify the connective tissue surgery process, improve the stripping efficiency, reduce the surgical difficulty, and shorten the operating time. Reduce bleeding and perforation complications caused by operating errors during surgery.
- the present invention provides the use of acetylcysteine or its chemically acceptable salt/ester in the preparation of connective tissue separation preparations.
- the connective tissue is the submucosa between the mucosal layer and the muscular layer of the digestive tract.
- Stomach wall The stomach wall is divided into 4 layers: 1Mucous membrane layer. It is the innermost layer of the stomach wall, rich in blood vessels, red in color, composed of a layer of columnar epithelial cells, with dense pits on the surface, located at the opening of a large number of glands in the mucosa. Columnar epithelial cells secrete mucus containing neutral polysaccharide mucin. There are still a large number of gastric glands in this layer. There are thin interwoven muscle bundles at the base of the gastric mucosal glands, called the muscularis mucosa. When the stomach is empty, the mucosa shows many folds. 2The submucosa is composed of loose connective tissue and elastic fibers.
- Muscle layer It includes three layers of muscle fibers in different directions.
- the inner layer is oblique fibers and the middle layer is circular fibers. It is the thickest in the pylorus and finally forms the exit sphincter.
- the outer layer is longitudinal fibers. 4Serosal layer. The peritoneal layer.
- the submucosa (submucosa) is a loose connective tissue, which contains small salivary glands, larger blood vessels, lymphatic vessels, nerves and adipose tissue, which mainly provides nutrition and support for the lamina propria.
- the separation preparation includes one or more of a separating agent, a dissolving agent, a filler, a protruding agent, and an adhesion release agent.
- the dosage of the acetylcysteine or its chemically acceptable salt/ester is 0.01 ⁇ 1.0 g/cm 2 connective tissue.
- the dosage form of the isolated preparation includes clinically acceptable solution preparations, emulsion preparations, injections, gels, environmentally responsive gels, capsules, tablets, pills, and granules. One or more of, granules, powders.
- the present invention also provides an isolated preparation of connective tissue, including acetylcysteine or a chemically acceptable salt/ester thereof and a chemical indicator.
- the effective concentration of the acetylcysteine or its chemically acceptable salt/ester is 1.0-20.0% (w/v).
- the dosage of the acetylcysteine or its chemically acceptable salt/ester is 0.01 ⁇ 1.0 g/cm 2 connective tissue.
- the connective tissue is the submucosa between the mucosal layer and the muscular layer of the digestive tract.
- the separation preparation includes one or more of a separating agent, a dissolving agent, a filler, a protruding agent, and an adhesion release agent.
- the present invention provides the use of acetylcysteine or its chemically acceptable salt/ester in the preparation of connective tissue separation preparations.
- the beneficial effects include but are not limited to:
- the invention discloses an application of acetylcysteine or a chemically acceptable salt/ester thereof in the preparation of a connective tissue separation preparation.
- the present invention provides the use of acetylcysteine or its chemically acceptable salts and esters in the preparation of connective tissue separation preparations.
- the acetylcysteine is N-acetyl-L-cysteine, and its structural formula is as shown in formula I:
- the connective tissue is the submucosa between the mucosal layer and the muscle layer of the digestive tract; it is filled between tissues and tissues, tissues and organs, organs and organs, and is loose connective tissue in the natural spaces between tissues and organs.
- the connective tissue separation preparation is a separating agent, a dissolving agent, a filler, a protruding agent, and an adhesion release agent that assists in surgical separation of tissue.
- the dosage form of the connective tissue separation preparation is clinically acceptable solution preparation, emulsion preparation, injection, gel, environmental response gel, capsule, tablet, pill, granule, granule, powder.
- the present invention uses 5.0% acetylcysteine solution + 0.002% bright blue, the average separation time of submucosal loose connective tissue is 11.6min, the average number of hemostasis is 0.2, the average number of injections is 2.0, and the average usage amount is 4.4ml.
- the control group there were 3 and 0 delayed bleeding wounds on the 2nd and 4th day after surgery.
- the wound healing rate at four weeks and eight weeks after operation were 59% and 100%, respectively, which were significantly better than those in the control group.
- the raw materials and reagents used in the application of acetylcysteine or its chemically acceptable salt/ester in the preparation of connective tissue separation preparations provided by the present invention can be purchased from the market.
- Experimental animals 60 pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg. Two days before the test, the residue feeding was stopped, and the sugary liquid food and water were fed.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 5.0% acetylcysteine solution + 0.002% brilliant blue
- the samples of the control group and the test group were injected submucosally at multiple points outside the marked points on the edge of the surgical site to lift the lesions and separate them from the muscle layer.
- Intraoperative bleeding can be stopped by electrocision or coagulation with a hemostatic forceps
- ESD endoscopic submucosal dissection
- ESD digestive tract
- esophagus esophagus
- stomach and intestine the control group used 0.9% physiological sodium chloride solution + 0.002% brilliant blue commonly used in clinical practice.
- the submucosal connective tissue separation time was 24.1 minutes on average.
- the average number of hemostasis was 1.0, the average number of injections was 4.2, and the average usage was 13.7ml.
- Experimental animals 60 pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg. Two days before the test, the residue feeding was stopped, and the sugary liquid food and water were fed.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 5.0% acetylcysteine solution + 0.002% brilliant blue
- the samples of the control group and the test group were injected submucosally at multiple points outside the marked points on the edge of the surgical site to lift the lesions and separate them from the muscle layer.
- Intraoperative bleeding can be stopped by electrocision or coagulation with hemostatic forceps
- Experimental animals 60 pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg. Two days before the test, the residue feeding was stopped, and the sugary liquid food and water were fed.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 5.0% acetylcysteine solution + 0.002% brilliant blue
- the samples of the control group and the test group were injected submucosally at multiple points outside the marked points on the edge of the surgical site to lift the lesions and separate them from the muscle layer.
- Intraoperative bleeding can be stopped by electrocision or coagulation with hemostatic forceps
- the control group uses 0.9% physiological sodium chloride solution + 0.002% brilliant blue, which is commonly used in clinical practice, and the wound healing rate is four weeks and eight weeks after the operation. The rates are 40% and 97%, respectively.
- Experimental animals 60 pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 10.0% acetylcysteine solution + 0.002% brilliant blue
- the samples of the control group and the test group were used to inject the connective tissue around the pancreas at multiple points to separate the pancreas from the surrounding tissues.
- pancreas Separate the pancreas from the surrounding tissues using the lateral edge of the pancreas with an electric knife. Over time, the injected fluid in the connective tissue will be gradually absorbed. If necessary, connective tissue injection can be repeated to maintain the separation of the pancreas from the surrounding tissues.
- Intraoperative bleeding can be stopped by electrocision or coagulation with hemostatic forceps
- control group used a filler that did not contain acetylcysteine to prepare the control group samples.
- the average separation time of pancreatic connective tissue was 85.9 minutes, and the average number of hemostasis was 2.87.
- pancreatic connective tissue of the preparation test group samples containing acetylcysteine was 31.8 minutes, and the average number of hemostasis was 0.577 times, which was significantly better than the control samples without acetylcysteine.
- Experimental animals 60 pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 20.0% acetylcysteine solution + 0.002% brilliant blue
- Sixty pigs for experimental animals were randomly divided into 2 groups, 30 in each group, and laparoscopic gallbladder dissection was performed respectively, using samples from the control group and the samples from the test group, respectively.
- the samples of the control group and the test group were used respectively.
- Multi-point injection is performed on the connective tissue around the gallbladder to separate the gallbladder from the surrounding tissues.
- Intraoperative bleeding can be stopped by electrocision or coagulation with hemostatic forceps
- control group used a filler that did not contain acetylcysteine to prepare the control group samples.
- the average separation time of gallbladder connective tissue was 46.3 minutes, and the average number of hemostasis was 1.87.
- the average separation time of gallbladder connective tissue in the preparation test group samples containing acetylcysteine was 23.9 minutes, and the average number of hemostasis was 0.37, which was significantly better than the control samples without acetylcysteine.
- Experimental animals 60 female pigs for experimental animals that have passed inspection and quarantine, weighing 32-36kg.
- Control sample 0.9% physiological sodium chloride solution + 0.002% brilliant blue
- Test group sample 1.0% acetylcysteine solution + 0.002% brilliant blue
- the samples of the control group and the test group were injected into the mucosa at multiple points outside the marked points on the edge of the surgical site, respectively, to lift the mucosal layer and separate it from the muscle layer.
- Intraoperative bleeding can be stopped by electrocision or coagulation with hemostatic forceps
- control group used a filler that did not contain acetylcysteine.
- the average submucosal connective tissue separation time of the control group sample was 28.5 minutes, and the average number of hemostasis was 1.63 times.
- the submucosal connective tissue separation time averaged 12.3 to 16.2 minutes, and the average number of hemostasis was 15.7 times, which was significantly better than the control samples without acetylcysteine.
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Abstract
本发明涉及医学制剂领域，特别涉及乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。本发明提供的乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用，简化结缔组织手术过程，降低手术难度，缩短手术时间，提高剥离效率，降低手术中操作失误导致出血、穿孔并发症。
Description
本申请要求于2020年01月20日提交中国专利局、申请号为202010064136.4、发明名称为“乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
本发明涉及医学制剂领域，特别涉及乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。
结缔组织是人体内柔软且富有弹性的组织，它充填在组织和器官之间，是组织器官的天然间隙。这种结缔组织在机体内分布非常广泛，它主要功能是支持，连接，营养，防御，保护以及修复创伤的作用。这些间隙对于外科手术，尤其是进行微创手术来讲尤为重要，因为在这些间隙里手术，层次清楚，是将组织或器官进行分离的理想位置。
外科/内镜手术中，层次暴露、病变剥离至关重要，分离包括机械钝性分离与高频电刀锐性分离，操作失误可能导致出血，穿孔等并发症。
因此，提供一种结缔组织分离制剂来简化手术过程，降低手术难度，缩短手术时间，操作失误可能导致出血，穿孔等并发症，具有重要的现实意义。
发明内容
有鉴于此，本发明提供一种乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。乙酰半胱氨酸或其化学上可接受的盐/酯在制得的结缔组织的分离制剂，能够简化结缔组织手术过程，提高剥离效率，降低手术难度，缩短手术时间。降低手术中操作失误导致出血、穿孔并发症。
为了实现上述发明目的，本发明提供以下技术方案：
本发明提供了乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。
在本发明的一些具体实施方案中，所述结缔组织为消化道的黏膜层与肌层之间的黏膜下层。
胃壁：胃壁分4层：①黏膜层。是胃壁最内层，富于血管，呈红色，由一层柱状上皮细胞组成，表面有密集小凹，位于黏膜内的大量腺体的腺管开口处。柱状上皮细胞分泌含有中性多糖黏蛋白的黏液。此层内尚有大量胃腺体。在胃黏膜腺体的基底部有薄层交织肌束，称之为黏膜肌层。胃排空时，黏膜呈现许多皱襞。②黏膜下层，为疏松结缔组织和弹性纤维所组成。内有丰富的血管和淋巴管以及Meissner神经网。③肌层。包括三层不同方向的肌纤维，内层是斜行纤维，中层是环行纤维，在幽门部最厚，终于形成出门括约肌。外层是纵行纤维。④浆膜层。即腹膜层。
黏膜下层(submucosa)为疏松结缔组织，内含小涎腺、较大的血管、淋巴管、神经及脂肪组织，主要是为固有层提供营养及支持。
在本发明的一些具体实施方案中，所述分离制剂包括分离剂、溶解剂、填充剂、隆起剂、粘连松解剂中的一种或多种。
在本发明的一些具体实施方案中，所述乙酰半胱氨酸或其化学上可接受的盐/酯的使用剂量为0.01～1.0g/cm
2结缔组织。
在本发明的一些具体实施方案中，所述分离制剂的剂型包括临床上可接受的溶液制剂、乳液制剂、注射剂、凝胶剂、环境响应凝胶剂、胶囊剂、片剂、丸剂、颗粒剂、冲剂、散剂中的一种或多种。
在上述研究的基础上，本发明还提供了结缔组织的分离制剂，包括乙酰半胱氨酸或其化学上可接受的盐/酯和化学指示剂。
在本发明的一些具体实施方案中，所述乙酰半胱氨酸或其化学上可接受的盐/酯的有效浓度为1.0～20.0％(w/v)。
在本发明的一些具体实施方案中，所述乙酰半胱氨酸或其化学上可接受的盐/酯的使用剂量为0.01～1.0g/cm
2结缔组织。
在本发明的一些具体实施方案中，所述结缔组织为消化道的黏膜层与 肌层之间的黏膜下层。
在本发明的一些具体实施方案中，所述分离制剂包括分离剂、溶解剂、填充剂、隆起剂、粘连松解剂中的一种或多种。
本发明提供了乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。有益效果包括但不限于：
1、简化结缔组织手术过程，提高剥离效率，降低手术难度，缩短手术时间。
2、降低手术中操作失误导致出血、穿孔并发症。
本发明公开了一种乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。
本发明提供了乙酰半胱氨酸或其化学上可接受的盐、酯在制备结缔组织分离制剂中的应用。
作为优选，所述乙酰半胱氨酸为N-乙酰-L-半胱氨酸，其结构式如式I所示：
作为优选，所述结缔组织为消化道黏膜层与肌层之间的黏膜下层；充 填在组织与组织、组织与器官、器官与器官之间，是组织器官的天然间隙的疏松结缔组织。
作为优选，所述结缔组织分离制剂为辅助手术分离组织的分离剂、溶解剂、填充剂、隆起剂、粘连松解剂。
作为优选，所结缔组织分离制剂的剂型为临床上可接受的溶液制剂、乳液制剂、注射剂、凝胶剂、环境响应凝胶剂、胶囊剂、片剂、丸剂、颗粒剂、冲剂、散剂。
本发明使用5.0％乙酰半胱氨酸溶液+0.002％亮蓝，黏膜下疏松结缔组织分离时间平均为11.6min、止血次数平均为0.2次、注射次数平均为2.0次和使用量平均为4.4ml，明显优于对照组。在60个创面中，术后第2天和第4天迟发性出血创面分别为3个和0个。术后第2天和第4天迟发红肿创面分别为7个和0个，明显优于对照组。术后四周创面愈合率和八周创面愈合率分别为59％和100％，明显优于对照组。
本发明提供的乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用中所用原料及试剂均可由市场购得。
下面结合实施例，进一步阐述本发明：
实施例1
1、试验动物：经检验检疫合格实验动物用猪60头，体重32-36kg。于试验前2天停止喂渣食，喂食含糖流食和清水。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：5.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪60头随机分成3组，每组20头，分别进行食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)。每头猪进行2处ESD手术，分别使用对照组样品和试验组样品。每个手术部位切除大小约为2cm×2cm。
4、试验步骤：
1)、标记
确定手术部位后，使用电切刀在手术部位进行电凝标记。
2)、黏膜下注射
分别对照组和试验组样品于手术部位边缘标记点外侧行多点黏膜下注射，将病灶抬起，与肌层分离。
3)、切开
使用电切刀沿标记点外侧缘切开黏膜。
4)、黏膜下结缔组织剥离
使用电切刀将黏膜下层结缔组织进行分离。随着时间延长，黏膜下注射的液体会被逐渐吸收，必要时可反复进行黏膜下注射以便维持黏膜的充分抬举。
5)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血；
6)、手术后创面处理
手术后，对创面可见出血点进行电凝止血处理；
5、试验的评价指标
(1)黏膜下结缔组织分离时间；
(2)黏膜下结缔组织剥离过程中止血次数；
(3)黏膜下结缔组织剥离过程中对照组样品和试验组样品的注射次数和使用量。
表1
注：与对照组相比**P＜0.01。
表1结果显示，乙酰半胱氨酸能够有效缩短黏膜下结缔组织分离时间，减少黏膜下结缔组织剥离过程中止血次数，减少黏膜下结缔组织剥离过程中对照组样品和试验组样品的注射次数和使用量。
在食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)过程中对照组使用目前临床常用0.9％生理氯化钠溶液+0.002％亮蓝，黏膜下结缔组织分离时间平均为24.1min、止血次数平均为1.0次、注射次数平均为4.2次和使用量平均为13.7ml。
使用5.0％乙酰半胱氨酸溶液+0.002％亮蓝，黏膜下结缔组织分离时间平均为11.6min、止血次数平均为0.2次、注射次数平均为2.0次和使用量平均为4.4ml，明显优于对照组。
用IBM spss statistics 23软件处理，T检验分析，结果显示，试验组与对照组在分离时间、止血次数、注射次数、注射数量，均差异极显著(P＜0.01)。
实施例2
1、试验动物：经检验检疫合格实验动物用猪60头，体重32-36kg。于试验前2天停止喂渣食，喂食含糖流食和清水。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：5.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪60头随机分成3组，每组20头，分别进行食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)。每头猪进行2处ESD手术，分别使用对照组样品和试验组样品。每个手术部位切除大小约为2cm×2cm。
4、试验步骤：
1)、标记
确定手术部位后，使用电切刀在手术部位进行电凝标记。
2)、黏膜下注射
分别对照组和试验组样品于手术部位边缘标记点外侧行多点黏膜下注射，将病灶抬起，与肌层分离。
3)、切开
使用电切刀沿标记点外侧缘切开黏膜。
4)、黏膜下结缔组织剥离
使用电切刀将黏膜下层结缔组织进行分离。随着时间延长，黏膜下注射的液体会被逐渐吸收，必要时可反复进行黏膜下注射以便维持黏膜的充分抬举。
5)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血
6)、手术后创面处理
手术后，对创面可见出血点进行电凝止血处理
5、试验的评价指标
(1)手术后创面迟发性出血情况(术后第2天、第7天观察)；
(2)手术后创面红肿情况(术后第2天、第7天观察)。
表2
注：不同小写字母表示在5％水平差异显著。
表2结果显示，使用乙酰半胱氨酸能够有效缩短黏膜下结缔组织分离时间，减少对创面的手术操作伤害，减少创面的迟发性出血和创面红肿，提高安全性。
在食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)过程中对照组使用目前临床常用0.9％生理氯化钠溶液+0.002％亮蓝，在60个对照组创 面中，术后第2天和第7天迟发性出血创面分别为13个和2个。术后第2天和第7天迟发红肿创面分别为28个和7个。
使用5.0％乙酰半胱氨酸溶液+0.002％亮蓝，在60个创面中，术后第2天和第4天迟发性出血创面分别为3个和0个。术后第2天和第4天迟发红肿创面分别为7个和0个，明显优于对照组。
用IBM spss statistics 23软件处理，卡方检验分析，结果显示，术后第2天迟发性出血，样品组与对照组有统计学意义，存在差异(P＜0.05)。术后第7天迟发性出血，样品组与对照组没有统计学意义不存在差异(P＞0.05)。术后第2天创面红肿：样品组与对照组，存在差异(P<0.05)。术后第7天创面红肿：样品组与对照组，存在差异(P<0.05)。
实施例3
1、试验动物：经检验检疫合格实验动物用猪60头，体重32-36kg。于试验前2天停止喂渣食，喂食含糖流食和清水。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：5.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪60头随机分成3组，每组20头，分别进行食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)。每头猪进行2处ESD手术，分别使用对照组样品和试验组样品。每个手术部位切除大小约为2cm×2cm。
4、试验步骤：
1)、标记
确定手术部位后，使用电切刀在手术部位进行电凝标记。
2)、黏膜下注射
分别对照组和试验组样品于手术部位边缘标记点外侧行多点黏膜下注射，将病灶抬起，与肌层分离。
3)、切开
使用电切刀沿标记点外侧缘切开黏膜。
4)、黏膜下结缔组织剥离
使用电切刀将黏膜下层结缔组织进行分离。随着时间延长，黏膜下注射的液体会被逐渐吸收，必要时可反复进行黏膜下注射以便维持黏膜的充分抬举。
5)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血
6)、手术后创面处理
手术后，对创面可见出血点进行电凝止血处理
5、试验的评价指标
手术后创面愈合情况(术后第4周、8周)。
表3
注：与对照组相比**P＜0.01。
表3结果显示，使用乙酰半胱氨酸能够有效缩短黏膜下结缔组织分离时间，减少对创面的手术操作伤害，提高创面愈合率。
在食道、胃和肠的消化道内镜黏膜下剥离手术(ESD)过程中对照组使用目前临床常用0.9％生理氯化钠溶液+0.002％亮蓝，术后四周创面愈合率和八周创面愈合率分别为40％和97％。
使用5.0％乙酰半胱氨酸溶液+0.002％亮蓝，术后四周创面愈合率和八周创面愈合率分别为59％和100％。，明显优于对照组。
用IBM spss statistics 23软件处理，T检验分析，结果显示术后四周创面愈合率，样品组与对照组差异极显著(P＜0.01)，术后八周创面愈合率，样品组与对照组差异极显著(P＜0.01)。
效果例4
1、试验动物：经检验检疫合格实验动物用猪60头，体重32-36kg。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：10.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪60头随机分成2组，每组30头，分别进行经腹腔镜下胰腺剥离手术，分别使用对照组样品和试验组样品。
4、试验步骤：
1)、造孔
在猪腹部的做2个直径10毫米的小切口，通过这些小切口插入摄像镜头和其他手术器械。
2)、注射
分别使用对照组样品和试验组样品于胰腺周围结缔组织行多点注射，使胰腺与周围组织分离。
3)、结缔组织剥离
使用电切刀胰腺外侧缘将胰腺与周围组织分离。随着时间延长，结缔组织中注射的液体会被逐渐吸收，必要时可反复进行结缔组织注射以便维持胰腺与周围组织分离分离。
4)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血
5、试验的评价指标
(1)胰腺周围结缔组织分离时间；
(2)胰腺周围结缔组织过程中止血次数；
表4
注：与对照组相比*P＜0.05。
表4结果表明，含有乙酰半胱氨酸的填充剂能够有效缩短胰腺周围结缔组织分离时间，减少胰腺周围结缔组织剥离过程中止血次数。
在胰腺周围结缔组织过程中对照组使用不含有乙酰半胱氨酸的填充剂制备对照组样品胰腺结缔组织分离时间平均为85.9min、止血次数平均为2.87次。
使用含有乙酰半胱氨酸的制备试验组样品胰腺结缔组织分离时间平均为31.8min、止血次数平均为0.577次，显优于不含有乙酰半胱氨酸的对照组样品。
用IBM spss statistics 23软件处理，T检验分析，试验组与对照组分离时间存在差异(P＜0.05)，试验组与对照组止血次数存在差异(P＜0.05)。
效果例5
1、试验动物：经检验检疫合格实验动物用猪60头，体重32-36kg。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：20.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪60头随机分成2组，每组30头，分别进行经腹腔镜下胆囊剥离手术，分别使用对照组样品和试验组样品。
4、试验步骤：
1)、造孔
在猪腹部的做2个直径10毫米的小切口，通过这些小切口插入摄像镜头和其他手术器械。
2)、注射
分别使用对照组样品和试验组样品。于胆囊周围结缔组织行多点注射，使胆囊与周围组织分离。
3)、结缔组织剥离
使用电切刀胆囊外侧缘将胆囊与周围组织分离。随着时间延长，结缔组织中注射的液体会被逐渐吸收，必要时可反复进行结缔组织注射以便维 持胆囊与周围组织分离分离。
4)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血
5、试验的评价指标
(1)胆囊周围结缔组织分离时间；
(2)胆囊周围结缔组织过程中止血次数；
表5
注：与对照组相比*P＜0.05。
表5结果表明，含有乙酰半胱氨酸的填充剂能够有效缩短胆囊周围结缔组织分离时间，减少胆囊周围结缔组织剥离过程中止血次数。
在胆囊周围结缔组织过程中对照组使用不含有乙酰半胱氨酸的填充剂制备对照组样品胆囊结缔组织分离时间平均为46.3min、止血次数平均为1.87次。
使用含有乙酰半胱氨酸的制备试验组样品胆囊结缔组织分离时间平均为23.9min、止血次数平均为0.37次，明显优于不含有乙酰半胱氨酸的对照组样品。
用IBM spss statistics 23软件分析，采用T检验，试验组与对照组胆囊结缔组织分离时间存在差异(P＜0.05)，试验组与对照组止血次数存在差异(P＜0.05)。
效果例6
1、试验动物：经检验检疫合格实验动物用雌猪60头，体重32-36kg。
2、试验样品：
对照组样品：0.9％生理氯化钠溶液+0.002％亮蓝
试验组样品：1.0％乙酰半胱氨酸溶液+0.002％亮蓝
3、试验方法：
将实验动物用猪30头随机分成2组，每组15头，进行宫腔镜内镜子宫内膜黏膜下剥离手术，每头猪进行2处手术，分别使用对照组样品和试验组样品。
4、试验步骤：
1)、标记
确定手术部位后，使用电切刀在手术部位进行电凝标记。
2)、黏膜下注射
分别使用对照组样品和试验组样品于手术部位边缘标记点外侧行多点黏膜下注射，将黏膜层抬起，与肌层分离。
3)、切开
使用电切刀沿标记点外侧缘切开黏膜。
4)、黏膜下结缔组织剥离
使用电切刀将黏膜下层结缔组织进行分离。随着时间延长，黏膜下注射的液体会被逐渐吸收，必要时可反复进行黏膜下注射以便维持黏膜的充分抬举。
5)、手术中出血处理
术中出血可采用电切刀电凝止血或止血钳止血
5、试验的评价指标
(1)黏膜下结缔组织分离时间；
(2)黏膜下结缔组织剥离过程中止血次数；
表6
注：与对照组相比*P＜0.05。
表6结果表明，含有乙酰半胱氨酸的填充剂能够有效缩短子宫内膜黏膜下剥离手术分离时间，减少子宫内膜黏膜下剥离过程中止血次数。
在子宫内膜黏膜下结缔组织过程中对照组使用不含有乙酰半胱氨酸的填充剂对照组样品黏膜下结缔组织分离时间平均为28.5min、止血次数 平均为1.63次。
使用含有乙酰半胱氨酸的试验组样品黏膜下结缔组织分离时间平均为12.3～16.2min、止血次数平均为15.7次，明显优于不含有乙酰半胱氨酸的对照组样品。
用IBM spss statistics 23软件处理，用T检验分析，试验组与对照组分离时间存在差异(P＜0.05)，试验组与对照组止血次数存在差异(P＜0.05)。
以上对本发明所提供的乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用进行了详细介绍。本文应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出，对于本技术领域技术人员来说，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这些改进和修饰也落入本发明权利要求的保护范围内。
Claims (10)
- 乙酰半胱氨酸或其化学上可接受的盐/酯在制备结缔组织的分离制剂中的应用。
- 如权利要求1所述的应用，其特征在于，所述结缔组织为疏松结缔组织和网状结缔组织。
- 如权利要求1或2所述的应用，其特征在于，所述分离制剂包括分离剂、溶解剂、填充剂、隆起剂、粘连松解剂中的一种或多种。
- 如权利要求1至3任一项所述的应用，其特征在于，所述乙酰半胱氨酸或其化学上可接受的盐/酯的使用剂量为0.01～1.0g/cm 2结缔组织。
- 如权利要求1至4任一项所述的应用，其特征在于，所述分离制剂的剂型包括临床上可接受的溶液制剂、乳液制剂、注射剂、凝胶剂、环境响应凝胶剂、胶囊剂、片剂、丸剂、颗粒剂、冲剂、散剂中的一种或多种。
- 结缔组织的分离制剂，其特征在于，包括乙酰半胱氨酸或其化学上可接受的盐/酯和化学指示剂。
- 如权利要求6所述的分离制剂，其特征在于，所述乙酰半胱氨酸或其化学上可接受的盐/酯的有效浓度为1.0～20.0％(w/v)。
- 如权利要求6或7所述的分离制剂，其特征在于，所述乙酰半胱氨酸或其化学上可接受的盐/酯的使用剂量为0.01～1.0g/cm 2结缔组织。
- 如权利要求6至8任一项所述的分离制剂，其特征在于，所述结缔组织为疏松结缔组织和网状结缔组织。
- 如权利要求6至9任一项所述的分离制剂，其特征在于，所述分离制剂包括分离剂、溶解剂、填充剂、隆起剂、粘连松解剂中的一种或多种。
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104689380A (zh) * | 2013-12-10 | 2015-06-10 | 复旦大学 | 一种由物理交联水凝胶构成的黏膜下注射材料及其应用 |
| CN105561402A (zh) * | 2016-01-13 | 2016-05-11 | 王兰周 | 一种内镜用黏膜下注入材料的配方及制备工艺 |
| CN106924809A (zh) * | 2017-03-20 | 2017-07-07 | 北京华信佳音医疗科技发展有限责任公司 | 一种i型胶原蛋白及液态黏膜下填充剂 |
| CN107456612A (zh) * | 2016-06-02 | 2017-12-12 | 山东威高药业股份有限公司 | 黏膜下注射溶液 |
| WO2019059237A1 (ja) * | 2017-09-25 | 2019-03-28 | 京都府公立大学法人 | ２剤型粘膜下注入用局注液 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140053881A (ko) * | 2011-04-19 | 2014-05-08 | 릭스하스피탈렛 | 모세관 누출의 예방 및 치료를 위한 수술 동안 투여되는 프로스타시클린 및 그 유사체 |
| EP3338813B1 (en) * | 2016-12-20 | 2020-01-29 | BSN Medical GmbH | Multi-layer wound care product with perforated release layer |
| EP4177342B1 (en) * | 2017-01-16 | 2023-12-27 | Spectrum Solutions L.L.C. | Nucleic acid preservation solution and methods of use |
-
2020
- 2020-01-20 CN CN202010064136.4A patent/CN113133996B/zh active Active
- 2020-12-30 WO PCT/CN2020/141351 patent/WO2021147634A1/zh active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104689380A (zh) * | 2013-12-10 | 2015-06-10 | 复旦大学 | 一种由物理交联水凝胶构成的黏膜下注射材料及其应用 |
| CN105561402A (zh) * | 2016-01-13 | 2016-05-11 | 王兰周 | 一种内镜用黏膜下注入材料的配方及制备工艺 |
| CN107456612A (zh) * | 2016-06-02 | 2017-12-12 | 山东威高药业股份有限公司 | 黏膜下注射溶液 |
| CN106924809A (zh) * | 2017-03-20 | 2017-07-07 | 北京华信佳音医疗科技发展有限责任公司 | 一种i型胶原蛋白及液态黏膜下填充剂 |
| WO2019059237A1 (ja) * | 2017-09-25 | 2019-03-28 | 京都府公立大学法人 | ２剤型粘膜下注入用局注液 |
Non-Patent Citations (4)
| Title |
|---|
| FENG, CHUN: "Research Progress on Submucosal Injection Solutions for Endoscopic Submucosal Dissection", CHINESE JOURNAL OF ANATOMY AND CLINICS, vol. 20, no. 6, 31 December 2015 (2015-12-31), CN, pages 584 - 587, XP009529235, ISSN: 2095-7041, DOI: 10.3760/cma.j.issn.2095-7041.2015.06.026 * |
| LU XIUHE, WANG CHUNHUI, XIE HUI, XIE YAN: "Research Progress on Submucosal Injection Materials for Endoscopic Surgery", CHINESE JOURNAL OF DIGESTIVE ENDOSCOPY, vol. 33, no. 9, 25 August 2016 (2016-08-25), pages 651 - 654, XP009529234, ISSN: 1674-2907, DOI: 10.3760/cma.j.issn.1007-5232.2016.09.024 * |
| REPICI ALESSANDRO; WALLACE MICHAEL; SHARMA PRATEEK; BHANDARI PRADEEP; LOLLO GIANLUCA; MASELLI ROBERTA; HASSAN CESARE; REX DOUGLAS : "A novel submucosal injection solution for endoscopic resection of large colorectal lesions: a randomized, double-blind trial.", GASTROINTESTINAL ENDOSCOPY, vol. 88, no. 3, 31 December 2018 (2018-12-31), pages 527 - 535+ 5, XP085446822, ISSN: 0016-5107, DOI: 10.1016/j.gie.2018.04.2363 * |
| YE XIAOSEN , JI FENG: "Research progress of submucosal injection materials in endoscopic submucosal dissection", INTERNATIONAL JOURNAL OF DIGESTIVE DISEASES, vol. 36, no. 4, 25 June 2016 (2016-06-25), pages 240 - 241, 251, XP009529338, ISSN: 1673-534X, DOI: 10.3969/j.issn.1673-534X.2016.04.013 * |
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