CN110638803A - Application of Dectichine in preparation of medicines for treating inflammatory bowel diseases - Google Patents
Application of Dectichine in preparation of medicines for treating inflammatory bowel diseases Download PDFInfo
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- CN110638803A CN110638803A CN201911112127.1A CN201911112127A CN110638803A CN 110638803 A CN110638803 A CN 110638803A CN 201911112127 A CN201911112127 A CN 201911112127A CN 110638803 A CN110638803 A CN 110638803A
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- Prior art keywords
- inflammatory bowel
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- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title abstract description 9
- 229940079593 drug Drugs 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 19
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 11
- 239000003651 drinking water Substances 0.000 description 8
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- 230000004083 survival effect Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 239000011886 peripheral blood Substances 0.000 description 3
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- 208000004232 Enteritis Diseases 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
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- 229910052751 metal Inorganic materials 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000003143 Panax notoginseng Nutrition 0.000 description 1
- 241000180649 Panax notoginseng Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229930182852 proteinogenic amino acid Natural products 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/185—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of biological medicine, in particular to application of Decicipine in preparation of a medicine for treating inflammatory bowel diseases.
Description
Technical Field
The invention relates to the field of biological medicine, in particular to application of Decicipine in preparation of a medicine for treating inflammatory bowel diseases.
Background
Inflammatory Bowel Disease (IBD) is a chronic recurrent disease characterized by nonspecific inflammatory lesions of the intestinal tract, including Ulcerative Colitis (UC) and Crohn's disease. By enteroscopy, congestion, edema, granular changes and even ulcer formation of the intestinal mucosa can be observed; extensive ulceration of the lesion area in histopathology is accompanied by massive neutrophil infiltration and necrosis of the intestinal mucosa. However, the pathogenesis of inflammatory bowel disease is currently not well defined and may be related to genetic susceptibility, external environmental stimuli, autoimmunity, and gut flora imbalance.
Denciphin is a non-proteinogenic amino acid isolated from Panax notoginseng (Burk.) F.H.Chen, and is capable of inhibiting the activity of HIF-prolylhydrolase-2 (PHD-2), and significantly inhibiting the cell proliferation of HBZY-1 cells and the accumulation of extracellular matrix (ECM) proteins, and reducing the secretion of collagen I (Col I), collagen type IV (Col IV) and Fibronectin (FN). Also, Decicihin can ameliorate metabolic disorders of diabetic nephropathy secondary to type II diabetes models.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a new application of Decicipine.
In a first aspect of the invention, there is provided the use of dentichine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of inflammatory bowel disease.
As the pharmaceutically acceptable salt, for example, a metal salt, a transition salt, a salt with an organic base, a salt with an inorganic acid, a salt with an organic acid, a salt with a basic or acidic amino acid, and the like can be mentioned. Non-limiting examples of metal salts include, but are not limited to, salts of alkali metals, such as sodium, potassium, and the like; salts of alkaline earth metals, such as calcium, magnesium, barium, aluminum and the like. Non-limiting examples of salts with inorganic acids include, but are not limited to, salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. Non-limiting examples of salts with organic acids include, but are not limited to, salts with formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, malic acid, maleic acid, tartaric acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like.
The inventor unexpectedly finds that Decicipine has a new application in treating inflammatory bowel disease as a quality medicament for diabetic nephropathy.
In a second aspect, the invention provides a pharmaceutical composition, which is characterized by containing a therapeutic amount of Decicipine or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable auxiliary materials.
The invention has the beneficial effects that the Decicipine has a good treatment effect on DSS (dextran sulfate sodium) induced enteritis of mice.
Drawings
Fig. 1 is a line graph showing survival of control (n-9) and treatment (n-6) mice after the start of oral administration of DSS drinking water;
fig. 2 is a scatter plot comparing the number of red blood cells in peripheral blood of mice 7 days after oral administration of DSS drinking water to the control group (n ═ 6) and the treated group (n ═ 6) mice;
fig. 3 is a scatter plot comparing the hematocrit in peripheral blood of mice 7 days after oral administration of DSS drinking water to the control (n-6) and treated (n-6) mice.
Detailed Description
The invention is illustrated but not limited by the following examples. The technical solutions protected by the present invention are all the simple replacements or modifications made by the skilled person in the art.
The material and the method are as follows:
mice: male wild type C57 mice (6-8 weeks) were purchased from the Chinese academy of sciences (Shanghai). All mice were housed in a Specific Pathogen Free (SPF) laboratory at the animal testing center of the second university of military medicine (shanghai). The treated mice were given 50ug/ml of Dentichine (purchased from Shanghai Yanxi Biotech Co., Ltd.) intraperitoneally for 3 consecutive days, and then given 1.5% DSS (40,000 kDa; ICN Biochemicals) drinking water orally for 7 days before being changed to normal drinking water. The control mice and the treated mice were treated with 1.5% DSS drinking water for 7 days at the same time and then changed to normal drinking water.
The life cycle experiment: survival of control (n-9) and treatment (n-6) mice was recorded from the start of oral administration of DSS drinking water. FIG. 1 shows that mice in the treatment group injected intraperitoneally with Dentichine had significantly better survival than the control group. The average survival days of the control mice were 9.2 days, and the average survival days of the Dentichine-treated mice were 11.8 days.
Peripheral blood analysis: on day 7 of the control group (n ═ 6) and the treatment group (n ═ 6) mice receiving 1.5% DSS water, the mice were anesthetized, and then subjected to apheresis by capillary tubes to be placed in centrifuge tubes (EP tubes) containing K2-EDTA. The red blood cells and hematocrit were determined by a standard hematology analyzer at the animal laboratory of the second department of medical and military university.
In conclusion, Decicipine has a good treatment effect on DSS (dextran sulfate sodium) induced enteritis in mice.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various changes and modifications can be made without departing from the inventive concept of the present invention, and these changes and modifications are all within the scope of the present invention.
Claims (2)
- Use of Decicipine, or a pharmaceutically acceptable salt thereof, in the treatment of inflammatory bowel disease.
- 2. A pharmaceutical composition characterized by comprising a therapeutic amount of Decicipine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019110168849 | 2019-10-24 | ||
| CN201911016884 | 2019-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110638803A true CN110638803A (en) | 2020-01-03 |
Family
ID=68995909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911112127.1A Pending CN110638803A (en) | 2019-10-24 | 2019-11-14 | Application of Dectichine in preparation of medicines for treating inflammatory bowel diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110638803A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110664814A (en) * | 2019-10-24 | 2020-01-10 | 上海长海医院 | Application of FG-4592 in preparation of medicines for treating inflammatory bowel diseases |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040138172A1 (en) * | 2001-06-01 | 2004-07-15 | Yukie Murata | Drug product for intestinal disease |
| US20090209565A1 (en) * | 2006-04-13 | 2009-08-20 | Taiho Pharmaceutical Co., Ltd. | Therapeutic agent for inflammatory bowel disease |
| CN104771387A (en) * | 2014-01-15 | 2015-07-15 | 上海中医药大学 | Use of dencichine |
-
2019
- 2019-11-14 CN CN201911112127.1A patent/CN110638803A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040138172A1 (en) * | 2001-06-01 | 2004-07-15 | Yukie Murata | Drug product for intestinal disease |
| US20090209565A1 (en) * | 2006-04-13 | 2009-08-20 | Taiho Pharmaceutical Co., Ltd. | Therapeutic agent for inflammatory bowel disease |
| CN104771387A (en) * | 2014-01-15 | 2015-07-15 | 上海中医药大学 | Use of dencichine |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110664814A (en) * | 2019-10-24 | 2020-01-10 | 上海长海医院 | Application of FG-4592 in preparation of medicines for treating inflammatory bowel diseases |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200103 |
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