CN103393669B - The application of Chukrasone B in the medicine of preparation prevention pancreatic gland fibrosis - Google Patents
The application of Chukrasone B in the medicine of preparation prevention pancreatic gland fibrosis Download PDFInfo
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- CN103393669B CN103393669B CN201310278043.1A CN201310278043A CN103393669B CN 103393669 B CN103393669 B CN 103393669B CN 201310278043 A CN201310278043 A CN 201310278043A CN 103393669 B CN103393669 B CN 103393669B
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- chukrasone
- pancreatic gland
- gland fibrosis
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- 229930187319 chukrasone Natural products 0.000 title claims abstract description 25
- 206010016654 Fibrosis Diseases 0.000 title claims abstract description 24
- 230000004761 fibrosis Effects 0.000 title claims abstract description 24
- 210000004907 gland Anatomy 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 230000002265 prevention Effects 0.000 title abstract description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 6
- 230000002946 anti-pancreatic effect Effects 0.000 abstract description 11
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 7
- 210000000496 pancreas Anatomy 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 4
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 4
- 229960002591 hydroxyproline Drugs 0.000 description 4
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 4
- 102000006628 Kv1.2 Potassium Channel Human genes 0.000 description 3
- 108010087141 Kv1.2 Potassium Channel Proteins 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001156380 Chukrasia tabularis Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- RSBNUWAVVQOBHL-UHFFFAOYSA-N C(CC)O.CC1=C(C(=O)O)C=CC=C1C(=O)O Chemical compound C(CC)O.CC1=C(C(=O)O)C=CC=C1C(=O)O RSBNUWAVVQOBHL-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- GGLZPLKKBSSKCX-UHFFFAOYSA-N S-ethylhomocysteine Chemical compound CCSCCC(N)C(O)=O GGLZPLKKBSSKCX-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004923 pancreatic tissue Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the application of Chukrasone B in preparation prevention or treatment pancreatic gland fibrosis medicine.The purposes of the Chukrasone B that the present invention relates in the anti-pancreatic gland fibrosis medicine of preparation belongs to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for pancreatic gland fibrosis inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, for anti-pancreatic gland fibrosis, obviously there is significant progress simultaneously.
Description
Technical field
The present invention relates to the application of Chukrasone B in pharmacy, particularly relate to Chukrasone B and prevent in preparation or treat the application in the medicine of pancreatic gland fibrosis.
Background technology
The current sickness rate of pancreatic gland fibrosis is more and more high, is badly in need of the anti-pancreatic gland fibrosis medicine of research and development high-efficiency low-toxicity.
The Compound C hukrasone B that the present invention relates to is one and delivers (Liu in 2012, H.B.et al., 2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers withNew Skeletons from Chukrasia tabularis.Organic Letters 14 (17), 4438 – 4441.) New skeleton compound, this compound has brand-new framework types, current purposes only relates to potassium-channel inhibit activities (Liu, H.B.et al., 2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers with New Skeletons fromChukrasia tabularis.Organic Letters 14 (17), 4438 – 4441.), the purposes of the Chukrasone B that the present invention relates in the anti-pancreatic gland fibrosis medicine of preparation is belonged to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for pancreatic gland fibrosis inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, for anti-pancreatic gland fibrosis, obviously there is significant progress simultaneously.
Summary of the invention
Technical problem to be solved by this invention is by designing animal experimental technique, the anti-pancreatic gland fibrosis effect of research Chukrasone B.
Described Compound C hukrasone B structure is as shown in formula I:
Therefore, the object of this invention is to provide Chukrasone B prevent in preparation or treat the application in the medicine of pancreatic gland fibrosis.
Positive progressive effect of the present invention is: Chukrasone B has the effect of anti-pancreatic gland fibrosis, so the application of Chukrasone B has good DEVELOPMENT PROSPECT.
The purposes of the Chukrasone B that the present invention relates in the anti-pancreatic gland fibrosis medicine of preparation belongs to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for pancreatic gland fibrosis inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, for anti-pancreatic gland fibrosis, obviously there is significant progress simultaneously.
Detailed description of the invention
The preparation method of Compound C hukrasone B involved in the present invention is see document (Liu, H.B.et al., 2012.Chukrasones A and B:Potential Kv1.2Potassium Channel Blockers with NewSkeletons from Chukrasia tabularis.Organic Letters 14 (17), 4438 – 4441.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of Compound C hukrasone B tablet involved in the present invention:
Get 20 g of compound Chukrasone B, add the customary adjuvant 180 grams preparing tablet, mixing, conventional tablet presses makes 1000.
Embodiment 2: the preparation of Compound C hukrasone B capsule involved in the present invention:
Get 20 g of compound Chukrasone B, add prepare capsule customary adjuvant as starch 180 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
Experimental example:
1 material
1.1 animal Wistar rats, male, body weight 180-200g.
1.2Chukrasone B dosage: 0.3mg/kg, 0.9mg/kg, 2.7mg/kg tri-dosage.
2 experimental techniques
2.1 modeling method Wistar rats, with lumbar injection dl-ethionine 250mg/ days, continuous 2 months, can occur that pancreas glandular cell reduces, adipocellular hypertrophy in interstitial.
2.2 grouping and medications
Rat model is divided into model group at random, and Chukrasone B 0.3mg/kg, 0.9mg/kg, 2.7mg/kg tri-dosage groups, separately establish blank group, start rear administration in modeling, oral continuous 30 days; Animal is dissected when 60 days.
2.3 Testing index
2.3.1 get pancreas at the end of experiment to weigh, calculate organ coefficient.
2.3.2 pancreas hydroxyproline content measures and gets the homogenate in water of 100mg sample, is hydrolyzed 20 hours in 110 DEG C of 10N HCl.HCl nitrogen volatilizees, and hydrolyzate filters after dissolving with distilled water.Get 0.5ml liquid to mix with the 1M periodic acid that 3ml citric acid phosphate buffer (0.15M citric acid adds 0.6M sodium hydrogen phosphate) and 0.5ml are dissolved in 9M phosphoric acid.Add 1.75ml Extraction buffer (5 parts of toluene: 5 parts of 2-methyl isophthalic acid-propanol: 2 parts of 1-propanol), concussion 30min, centrifugal.Organize phase (0.6ml) and Ehrlich
,15min is placed in the mixing of s reagent.Measure trap at 565nm, with 4-hydroxyl-1-proline production standard curve calculating concentration, content represents with ug/g tissue.
2.3.3 histological examination pancreatic tissues 10% formalin is fixed, paraffin embedding, microscopy after dyeing.To inflammatory cell infiltration, interstitial edema, fibrosis, pancreas room necrocytosis, and bleeding scoring (0-3 divides).
3 results
3.1Chukrasone B is on the impact of rat pancreas weight and organ coefficient
At the end of experiment, rat put to death, dissect, to weigh in and pancreas weighs and calculates the ratio of itself and body weight, the results are shown in Table 1.Chukrasone B, on the impact of pancreas organ coefficient, compares with model group and has significant difference.
Table 1
* represent p<0.05, compare with model group
3.2 pancreas hydroxyproline contents measure
During experimental result, carry out pulmonary's hydroxyproline content mensuration to each group of rat, result is as table 2.Chukrasone B, on the impact of hydroxyproline content, compares with model group and has significant difference.
Table 2
* represent p<0.05, compare with model group
3.3 histological examination
At the end of experiment, rat put to death, dissect; The embedding of specimen routine, fixing, HE dyeing, microscopy.
Result: model group visible pancreas surrounding catheter extensive inflammation reaction in the 60th day; Addicted to middle granulocyte karyolymph cellular infiltration, interstitial edema, hemorrhage and accidental pancreas cystencyte is downright bad; Fibrosis is there is between pancreas cystencyte disappearance position and pancreas bubble.
Chukrasone B can reduce inflammatory reaction, tissue edema and fibrosis by dose dependent.Appraisal result is in table 3.Chukrasone B, on the impact of scoring, compares with model group and has significant difference.
Table 3
* represent p<0.05, compare with model group
Conclusion: the present invention on the Fibrotic impact of pancreas in rat, confirms that ChukrasoneB has the effect of anti-pancreatic gland fibrosis by Chukrasone B.Therefore, Chukrasone B can be used as the medicine of active component for the preparation of anti-pancreatic gland fibrosis.
Claims (1)
- The application of 1.Chukrasone B in preparation treatment pancreatic gland fibrosis medicine, described Compound C hukrasone B structure as formula Ishown in:formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310278043.1A CN103393669B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone B in the medicine of preparation prevention pancreatic gland fibrosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310278043.1A CN103393669B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone B in the medicine of preparation prevention pancreatic gland fibrosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103393669A CN103393669A (en) | 2013-11-20 |
| CN103393669B true CN103393669B (en) | 2015-08-19 |
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| CN201310278043.1A Active CN103393669B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone B in the medicine of preparation prevention pancreatic gland fibrosis |
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| Country | Link |
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| CN (1) | CN103393669B (en) |
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| Publication number | Publication date |
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Effective date of registration: 20171115 Address after: 401120 Chongqing Yubei District Food City Avenue 18 Chongqing advertising industrial park office space Patentee after: Chongqing San Mou science and Technology Development Co., Ltd. Address before: 210009 Gulou District, Jiangsu, Nanjing Gu Ping Kong, No. 4 Patentee before: Ding Shengyu |
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Effective date of registration: 20201230 Address after: 224200 No.88 Gangcheng Avenue, Dongtai coastal economic zone, Yancheng City, Jiangsu Province Patentee after: Dongtai Haibin science and Technology Pioneer Park Management Co., Ltd Address before: 401120 office building of Chongqing advertising industrial park, No.18, shifucheng Avenue, Yubei District, Chongqing Patentee before: CHONGQING SUMARTE TECHNOLOGY DEVELOPMENT Co.,Ltd. |