CN102872126B - Application of Houttuynoid E in medicament for preventing or treating pancreatic fibrosis - Google Patents
Application of Houttuynoid E in medicament for preventing or treating pancreatic fibrosis Download PDFInfo
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- CN102872126B CN102872126B CN201210419464.7A CN201210419464A CN102872126B CN 102872126 B CN102872126 B CN 102872126B CN 201210419464 A CN201210419464 A CN 201210419464A CN 102872126 B CN102872126 B CN 102872126B
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- houttuynoid
- pancreatic fibrosis
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- medicament
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- VCNWTZPWIVDHGN-SLBJRTIWSA-N 2-[4,5-dihydroxy-2-(2-oxoundecyl)phenyl]-5,7-dihydroxy-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound CCCCCCCCCC(=O)CC1=CC(O)=C(O)C=C1C1=C(O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 VCNWTZPWIVDHGN-SLBJRTIWSA-N 0.000 title claims abstract description 58
- 206010016654 Fibrosis Diseases 0.000 title claims abstract description 24
- 230000004761 fibrosis Effects 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 210000004907 gland Anatomy 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 9
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 5
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 5
- 229960002591 hydroxyproline Drugs 0.000 claims description 5
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 5
- GGLZPLKKBSSKCX-UHFFFAOYSA-N S-ethylhomocysteine Chemical compound CCSCCC(N)C(O)=O GGLZPLKKBSSKCX-UHFFFAOYSA-N 0.000 claims description 2
- 230000002946 anti-pancreatic effect Effects 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 5
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 210000000496 pancreas Anatomy 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 208000009889 Herpes Simplex Diseases 0.000 description 4
- 241000700584 Simplexvirus Species 0.000 description 4
- 230000003602 anti-herpes Effects 0.000 description 4
- 240000000691 Houttuynia cordata Species 0.000 description 3
- 235000013719 Houttuynia cordata Nutrition 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
- 229930003935 flavonoid Natural products 0.000 description 3
- 150000002215 flavonoids Chemical class 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 229930190556 houttuynoid Natural products 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000002265 prevention Effects 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
- 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
- 230000034994 death Effects 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
- 229920002472 Starch Polymers 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000004364 calculation method Methods 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
- 238000005516 engineering process Methods 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
- 230000017074 necrotic cell death Effects 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
- 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
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of Houttuynoid E in preparing a medicament for preventing or treating pancreatic fibrosis. The use of Houttuynoid E in preparing the anti-pancreatic fibrosis medicament involved in the invention is disclosed for the first time; as the framework type of Houttuynoid E is a brand new framework type and Houttuynoid E has an unexpectedly high inhibition activity for the pancreatic fibrosis without possibility of giving any implication by other compounds, Houttuynoid E has outstanding substantive features; and simultaneously, the application of Houttuynoid E for preventing the pancreatic fibrosis apparently has obvious progress.
Description
Technical field
The present invention relates to the application of Houttuynoid E in pharmacy, relate in particular to the application of Houttuynoid E in the medicine of preparation prevention or treatment 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 H outtuynoid E the present invention relates to is one and within 2012, delivers (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.) New skeleton compound, this compound has brand-new framework types, current purposes only relates to anti-herpes simplex virus activity (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.), it is open first that purposes for the Houttuynoid E the present invention relates in the anti-pancreatic gland fibrosis medicine of preparation belongs to, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for pancreatic gland fibrosis, there is not the possibility that is 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 Houttuynoid E.
Described compound H outtuynoid E structure is as shown in formula I:
Formula I
Therefore, the object of this invention is to provide the application of Houttuynoid E in the medicine of preparation prevention or treatment pancreatic gland fibrosis.
Positive progressive effect of the present invention is: Houttuynoid E has the effect of anti-pancreatic gland fibrosis, so the application of Houttuynoid E has good DEVELOPMENT PROSPECT.
The purposes of the Houttuynoid E the present invention relates in the anti-pancreatic gland fibrosis medicine of preparation belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for pancreatic gland fibrosis, there is not the possibility that is provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, for anti-pancreatic gland fibrosis, obviously there is significant progress simultaneously.
The specific embodiment
The preparation method of compound H outtuynoid E involved in the present invention is referring to document (Chen, S. D. et al., 2012. Houttuynoid E_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound H outtuynoid E tablet involved in the present invention:
Get 20 and digest compound Houttuynoid E, add 180 grams of conventional adjuvants preparing tablet, mix, conventional tablet machine is made 1000.
Embodiment 2: the preparation of compound H outtuynoid E capsule involved in the present invention:
Get 20 and digest compound Houttuynoid E, add the conventional adjuvant of preparing capsule as 180 grams of starch, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
Experimental example:
1 material
1.1 animal Wistar rats, male, body weight 180-200g.
1.2 Houttuynoid E dosage: 0.3mg/kg, 0.9mg/kg, tri-dosage of 2.7mg/kg.
2 experimental techniques
2.1 modeling method Wistar rats, with lumbar injection dl-ethionine 250 mg/ 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 Houttuynoid E 0.3mg/kg, 0.9mg/kg, tri-dosage groups of 2.7mg/kg, separately establish blank group, in modeling, starts rear administration, oral continuous 30 days; In the time of 60 days, dissect animal.
2.3 detect index
When 2.3.1 experiment finishes, get pancreas and weigh, calculate organ coefficient.
2.3.2 pancreas hydroxyproline content is measured and is got the homogenate in water of 100mg sample, in 110 ℃ of 10 N HCl, is hydrolyzed 20 hours.HCl volatilizees with nitrogen, and hydrolyzate filters after dissolving with distilled water.Getting 0.5ml liquid mixes 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 is centrifugal.Organize phase (0.6ml) and Ehrlich
,s reagent mix is placed 15min.At 565nm, measure trap, by 4-hydroxyl-1-proline production standard curve calculation concentration, content represents with ug/g tissue.
2.3.3 histological examination pancreas tissue is fixed with 10% formalin, paraffin embedding, microscopy after dyeing.To inflammatory cell infiltration, interstitial edema, fibrosis, pancreas room necrocytosis, and bleeding scoring (0-3 divides).
3 results
3.1 impacts of Houttuynoid E on rat pancreas weight and organ coefficient
When experiment finishes, rat is put to death, dissected, weigh in and pancreas weighs and calculate the ratio of itself and body weight, the results are shown in Table 1.The impact of Houttuynoid E on pancreas organ coefficient, relatively has significant difference with model group.
Table 1
* represent p<0.05, with model group comparison
3.2 pancreas hydroxyproline contents are measured
During experimental result, each group of rat carried out to pulmonary's hydroxyproline content mensuration, result is as table 2.The impact of Houttuynoid E on hydroxyproline content, relatively has significant difference with model group.
Table 2
* represent p<0.05, with model group comparison
3.3 histological examination
When experiment finishes, rat is put to death, dissected; The conventional embedding of specimen, fixing, HE dyeing, microscopy.
Result: model group visible pancreas conduit serious inflammatory reaction around in the 60th day; Have a liking for middle granulocyte karyolymph cellular infiltration, interstitial edema, the necrosis of hemorrhage and accidental pancreas cystencyte; Between pancreas cystencyte disappearance position and pancreas bubble, there is fibrosis.
Houttuynoid E can reduce inflammatory reaction, tissue edema and fibrosis by dose dependent.Appraisal result is in Table 3.The impact of Houttuynoid E on scoring, relatively has significant difference with model group.
Table 3
* represent p<0.05, with model group comparison
Conclusion: the present invention on the Fibrotic impact of pancreas in rat, has confirmed that Houttuynoid E has the effect of anti-pancreatic gland fibrosis by Houttuynoid E.Therefore, Houttuynoid E can be used as the medicine of active component for the preparation of anti-pancreatic gland fibrosis.
Claims (1)
1.Houttuynoid E reduces the application in hydroxyproline content medicine in the pancreatic gland fibrosis that dl-ethionine causes in preparation, described compound H outtuynoid E structure as
formula Ishown in:
formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210419464.7A CN102872126B (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid E in medicament for preventing or treating pancreatic fibrosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210419464.7A CN102872126B (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid E in medicament for preventing or treating pancreatic fibrosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102872126A CN102872126A (en) | 2013-01-16 |
| CN102872126B true CN102872126B (en) | 2014-04-16 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210419464.7A Active CN102872126B (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid E in medicament for preventing or treating pancreatic fibrosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102872126B (en) |
-
2012
- 2012-10-27 CN CN201210419464.7A patent/CN102872126B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Chen SD,et al.Houttuynoids A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata.《ORGANIC LETTERS》.2012,第14卷(第7期),第1772-1775页. |
| Houttuynoids A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata;Chen SD,et al;《ORGANIC LETTERS》;20120406;第14卷(第7期);第1772-1775页 * |
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| Publication number | Publication date |
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| CN102872126A (en) | 2013-01-16 |
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