CN116059206A - Application of 2-aminoquinoline in medicine for treating diarrhea - Google Patents
Application of 2-aminoquinoline in medicine for treating diarrhea Download PDFInfo
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- CN116059206A CN116059206A CN202310197631.6A CN202310197631A CN116059206A CN 116059206 A CN116059206 A CN 116059206A CN 202310197631 A CN202310197631 A CN 202310197631A CN 116059206 A CN116059206 A CN 116059206A
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- aminoquinoline
- diarrhea
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- mouse
- mice
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- GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical compound C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-N 0.000 title claims abstract description 64
- 206010012735 Diarrhoea Diseases 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 11
- 235000006693 Cassia laevigata Nutrition 0.000 abstract description 8
- 229940124513 senna glycoside Drugs 0.000 abstract description 8
- 230000008602 contraction Effects 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 210000001072 colon Anatomy 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 229940126585 therapeutic drug Drugs 0.000 abstract description 2
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 abstract 1
- 241000735631 Senna pendula Species 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 12
- 241000522641 Senna Species 0.000 description 7
- 230000000968 intestinal effect Effects 0.000 description 7
- 210000003608 fece Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 210000002784 stomach Anatomy 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 230000013872 defecation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 150000005010 aminoquinolines Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- DGQLVPJVXFOQEV-JNVSTXMASA-N carminic acid Chemical compound OC1=C2C(=O)C=3C(C)=C(C(O)=O)C(O)=CC=3C(=O)C2=C(O)C(O)=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DGQLVPJVXFOQEV-JNVSTXMASA-N 0.000 description 2
- 230000002550 fecal effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 239000006041 probiotic Substances 0.000 description 2
- 235000018291 probiotics Nutrition 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XOGPDSATLSAZEK-UHFFFAOYSA-N 2-Aminoanthraquinone Chemical compound C1=CC=C2C(=O)C3=CC(N)=CC=C3C(=O)C2=C1 XOGPDSATLSAZEK-UHFFFAOYSA-N 0.000 description 1
- QKJAZPHKNWSXDF-UHFFFAOYSA-N 2-bromoquinoline Chemical compound C1=CC=CC2=NC(Br)=CC=C21 QKJAZPHKNWSXDF-UHFFFAOYSA-N 0.000 description 1
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- 241001237204 Leucopaxillus albissimus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940125714 antidiarrheal agent Drugs 0.000 description 1
- 239000003793 antidiarrheal agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004953 colonic tissue Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000001955 intestinal smooth muscle cell Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- PBQZDVLJNWXNFO-UHFFFAOYSA-N n-benzylquinolin-2-amine Chemical compound C=1C=C2C=CC=CC2=NC=1NCC1=CC=CC=C1 PBQZDVLJNWXNFO-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61P1/12—Antidiarrhoeals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an application of 2-aminoquinoline in a diarrhea treatment drug, wherein 2-aminoquinoline is adopted to treat a senna-induced C57BL/6J mouse diarrhea model, the related parameters of the mouse diarrhea and the whole gastrointestinal tract transit time are improved, and dynamics research shows that the 2-aminoquinoline can reduce the contraction amplitude and frequency of colon tissues of the mouse. The invention provides a new method for preparing the therapeutic drugs for diarrhea and related diseases.
Description
Technical Field
The invention belongs to the field of chemical drugs, and in particular relates to application of 2-aminoquinoline in a medicine for treating diarrhea.
Background
Diarrhea (diaorrhea) is a common symptom, and means that the defecation frequency is obviously higher than that of daily habit, the feces are thin, the water content is increased, the daily defecation amount is higher than 200g, or undigested food, purulent blood and mucus are contained. Despite significant advances in health and public health awareness, diarrhea is one of the major causes of disease burden worldwide. The occurrence of diarrhea is closely related to intestinal flora, and improving intestinal flora by oral probiotic or fecal transplantation is widely used for treating diarrhea. Common treatment means for diarrhea include antibiotics, mucous membrane protectants, antidiarrheals, probiotics and the like, but have the problems of low effective rate, re-unbalance of intestinal flora, serious side effects after long-term application and the like, and pharmaceutical economics and the like. Therefore, the research of the intestinal bacteria metabolites for standardization, standardization and objectification of diarrhea treatment is enhanced from the urgent need of searching the interaction path between the intestinal bacteria and human bodies from the intestinal specific bacteria, and the method has very important significance for diarrhea prevention and treatment.
2-Aminoquinoline (2-amino-quinone) also known as oxamine, N-di-2-propenyl-1, 3, 5-triazine-2, 4, 6-triamine N-oxide, formula: C9H8N2, molar mass is 144.17, is a flaky solid, is slightly soluble in water, and is easily soluble in ethanol, diethyl ether, chloroform and hot water. The 2-aminoquinoline is separated and identified from the extract of pure white mushroom (Leucopaxillus albissimus) at the earliest time and shows in-vitro antibacterial activity on pseudomonas baumannii and burkholderia cepacia. In addition to biological sources, 2-aminoquinoline is used as a chemical substance, and industrial synthesis methods thereof are various and in continuous improvement, and 2-bromoquinoline, 2-chloroquinoline, 4-methylpyridine, benzyl-quinolin-2-yl-amine and the like are known as synthesis raw materials. Because quinoline ring has stronger pharmacological and physiological activities and shows good biological and pharmacological activities, the prior researches show that the structure is introduced into some common drug molecules, and the quinoline ring has certain antibacterial, antiviral, analgesic and antitumor effects. However, the role and mechanism by which 2-aminoquinoline plays in diarrhea is still unclear.
Disclosure of Invention
The invention aims to provide an application of 2-aminoquinoline in a medicament for treating diarrhea.
The invention also aims to provide a safe dose of the 2-aminoquinoline for treating diarrhea.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
the application of 2-aminoquinoline in the preparation of a medicament for treating diarrhea.
The dosage of the 2-aminoquinoline is 20mg/kg-30mg/kg.
Compared with the prior art, the invention has the following advantages:
based on the pharmacological action, the 2-aminoquinoline can improve diarrhea by inhibiting intestinal smooth muscle cell contraction, and has very important significance for developing a targeted, accurate, safe and effective drug monomer and mixture as a therapeutic drug for diarrhea and related diseases.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention. In the drawings:
figure 1 2-aminoquinoline reduced senna leaf induced diarrhea mice model graph, wherein left graph is stool water content, right graph is total gastrointestinal transit time;
FIG. 2 2-aminoquinoline inhibits frequency and frequency of colon contractions in mice ex vivo.
Detailed Description
The following detailed description is exemplary and is intended to provide further explanation of the invention. It will be understood by those skilled in the art that various changes and substitutions can be made in the details and form of the technical solution of the present invention without departing from the spirit and scope of the invention, but these changes and substitutions fall within the scope of the present invention.
The experimental animals used in the invention and the chemical reagents are all commercially available raw materials for routine experiments.
Example 1 2 toxicity test of aminoquinoline;
the mice are infused with 30mg/kg of 2-aminoquinoline in one day, the general condition of the mice is observed to be good, the mice are continuously observed for 14 days, no animal dies, and the anatomical observation viscera are not abnormal, which indicates that the 2-aminoquinoline has low toxicity and safety.
EXAMPLE 2.2 Effect of aminoquinoline on treatment of diarrhea
The experimental animals selected in the experiment are SPF-class 8-week-old male C57BL/6J mice, and the weight is 18-20g; 2-aminoquinoline is selected into a dosage of 20mg/kg-30mg/kg, and C57BL/6G mice with the age of 8 weeks are irrigated; the stomach is continuously irrigated for one week, the stomach is irrigated once a day, physiological saline is simultaneously arranged as a control group, after the last time of the drug irrigation, the stomach is irrigated by using carmine red solvent, after 40 minutes, the total gastrointestinal transit time is recorded, and the result shows that the total gastrointestinal transit time of the mice after the 2-aminoquinoline is irrigated is prolonged, thus indicating that the 2-aminoquinoline has the effect of inhibiting gastrointestinal motility.
Mice were randomized into the senna group, the 2-aminoquinoline treated group and the control group after 4 hours of starvation. The senna leaf group is given 50 μl of senna leaf to each mouse, the treatment group is given 50 μl of senna leaf and 20-30 mg/kg of 2-aminoquinoline to each mouse, the control group is given 50 μl of PBS solution to each mouse, after molding is completed for 4 hours, the defecation condition of the mice is firstly evaluated, fresh feces of the mice are weighed and then dried for a certain time until the quality is unchanged, then the feces water content of the mice is calculated, the feces water contents of the mice in the 2-aminoquinoline group, the senna leaf group and the control group are compared, and after the carmine red solvent is used for stomach irrigation, the total gastrointestinal tract transit time is recorded. See fig. 1, which shows that the fecal moisture content of the 2-aminoquinoline group is reduced compared to the control group mice. The results show that the water content of the feces of the 2-aminoquinoline group is reduced compared with that of the PBS group, and the total gastrointestinal tract transit time is prolonged.
Taking the colon tissue of the model of the senna She Fuxie, carrying out 2-aminoquinoline in-vitro perfusion experiments, and measuring the contraction frequency and amplitude of the in-vitro colon tissue. The results showed a decrease in the frequency and magnitude of colonic tissue contraction of the 2-aminoquinoline group.
The above results all confirm that 2-aminoquinoline can relieve diarrhea, and that 2-aminoquinoline can relieve diarrhea by inhibiting intestinal smooth muscle contraction.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (2)
- Use of 2-aminoquinoline in the treatment of diarrhea.
- 2. Use of 2-aminoquinoline according to claim 1 in a medicament for the treatment of diarrhoea, wherein the dose of 2-aminoquinoline is from 20mg/kg to 30mg/kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310197631.6A CN116059206A (en) | 2023-03-03 | 2023-03-03 | Application of 2-aminoquinoline in medicine for treating diarrhea |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310197631.6A CN116059206A (en) | 2023-03-03 | 2023-03-03 | Application of 2-aminoquinoline in medicine for treating diarrhea |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116059206A true CN116059206A (en) | 2023-05-05 |
Family
ID=86176839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310197631.6A Pending CN116059206A (en) | 2023-03-03 | 2023-03-03 | Application of 2-aminoquinoline in medicine for treating diarrhea |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116059206A (en) |
-
2023
- 2023-03-03 CN CN202310197631.6A patent/CN116059206A/en active Pending
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