CN103933034B - A kind of pharmaceutical composition and application containing luteolin - Google Patents
A kind of pharmaceutical composition and application containing luteolin Download PDFInfo
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- CN103933034B CN103933034B CN201410137572.4A CN201410137572A CN103933034B CN 103933034 B CN103933034 B CN 103933034B CN 201410137572 A CN201410137572 A CN 201410137572A CN 103933034 B CN103933034 B CN 103933034B
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- Prior art keywords
- luteolin
- pharmaceutical composition
- olmesartan medoxomil
- group
- olmesartan
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- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 title claims abstract description 47
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 title claims abstract description 43
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 235000009498 luteolin Nutrition 0.000 title claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 claims abstract description 27
- 229960001199 olmesartan medoxomil Drugs 0.000 claims abstract description 27
- 206010020772 Hypertension Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 6
- 230000001631 hypertensive effect Effects 0.000 claims description 5
- 229940112973 olmesartan medoxomil 10 mg Drugs 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000036772 blood pressure Effects 0.000 abstract description 7
- 230000008878 coupling Effects 0.000 abstract description 3
- 238000010168 coupling process Methods 0.000 abstract description 3
- 238000005859 coupling reaction Methods 0.000 abstract description 3
- 108010022579 ATP dependent 26S protease Proteins 0.000 abstract description 2
- 208000007530 Essential hypertension Diseases 0.000 abstract description 2
- 230000007211 cardiovascular event Effects 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract description 2
- 241000700159 Rattus Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000890 drug combination Substances 0.000 description 5
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 4
- 241000628997 Flos Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000005480 Olmesartan Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 229960005117 olmesartan Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000119904 Elsholtzia blanda Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 150000002555 kaempferol Chemical class 0.000 description 1
- 235000008777 kaempferol Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- -1 luteolin compound Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000004873 systolic arterial blood pressure Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition and the purposes that contain luteolin, the active component of this pharmaceutical composition is made up of olmesartan medoxomil and luteolin, and the weight ratio of preferred olmesartan medoxomil and luteolin is 1:2-20.Adopt the luteolin coupling olmesartan medoxomil of low dosage slowly and reduce blood pressure reposefully, thus the protection of target organs of patients with essential hypertension 26S Proteasome Structure and Function can be conducive to, reduce the incidence rate of cardiovascular event further.
Description
Technical field
The invention belongs to medical art, relate to a kind of pharmaceutical composition, particularly a kind of pharmaceutical composition and application containing low dose of luteolin.
Background technology
Hypertension is modal cardiovascular disease, and oneself becomes the great public health problem in global range.According to the statistics display of national hygiene department, to the end of the year 2006, China patients with hypertension crowd will have reached 1.6 hundred million people, and annual newly-increased patient more than 3,000,000.
Hypertension is the syndrome that a cause of disease and pathogenesis are very complicated, once making a definite diagnosis, namely needs lifelong medication.At present, domestic and international medical circle is generally tended to the antihypertensive use in conjunction of two kinds of different mechanism of action.Report for 6th time according to U.S.'s prevention, check and evaluation and the treatment hypertension National Committee, the compound preparation that these antihypertensive low doses are fixed not only can be used as Second line Drug, also can be used as first-line drug for hypertensive treatment, more should be like this when especially patient has other complication or complication to exist simultaneously." the Chinese hypertension prevention and control guide (originally practical) in 2004 " of China's revision in 2004 is thought, adopt fixed mixing ratio compound recipe, its advantage is convenient, is conducive to the compliance improving patient.
Olmesartan medoxomil (olmesartanmedoxomil) is a kind of new A ng II receptor antagonist, chemical name 4-(1-hydroxyl-1-Methylethyl)-2-propyl group-1-[2 '-(tetrazolium-5-base) phenyl] Methylimidazole .-5-carboxylic acid, goes ester to change into active metabolite Olmesartan (olmesartan) completely at small bowel after it is oral and plays the effect of blood pressure lowering.The chemistry by name 3 of luteolin (luteolin), 4,5,7 kaempferols, it is a kind of faintly acid kaempferol compounds, widely distributed in plant kingdom, be present in many natural drugs such as Folium Perillae, Flos Lonicerae, Flos Chrysanthemi, Elsholtzia blanda, Flos Lonicerae, Herba Apii graveolentis, cabbage, cauliflower, Radix Dauci Sativae and veterinary antibiotics, there is antitumor, antiinflammatory, the effect such as antibacterial.Luteolin is used for the aspect such as antiinflammatory, antitumor, about luteolin, the biological activity of blood pressure is had no report.
At present, prior art does not also have the report about olmesartan medoxomil and luteolin use in conjunction, antihypertensive report after use in conjunction both especially not having.
Summary of the invention
According to the latest notion in recent clinical trial and hypertension therapeutic field, the present inventor in conjunction with the Therapeutic Characteristics of existing antihypertensive drug, and creatively proposes olmesartan medoxomil and luteolin to combine to be used for the treatment of hypertension according to results of animal.Therefore, the object of the present invention is to provide one to treat hypertensive pharmaceutical composition, specifically, the invention provides a kind of pharmaceutical composition and the application that contain low dose of luteolin.
The object of the present invention is achieved like this:
A pharmaceutical composition containing luteolin, this pharmaceutical composition is prepared from by active component and pharmaceutic adjuvant, and wherein said active component is made up of olmesartan medoxomil and luteolin.
Preferably, pharmaceutical composition as above, wherein the weight ratio of olmesartan medoxomil and luteolin is 1:2-20.
Further preferably, pharmaceutical composition as above, wherein the weight ratio of olmesartan medoxomil and luteolin is 1:5-10.
Again further preferably, pharmaceutical composition as above, wherein the weight ratio of olmesartan medoxomil and luteolin is 1:10.
Pharmaceutical composition of the present invention is preferably prepared into solid orally ingestible, as tablet, capsule.Further preferably, wherein per unit solid orally ingestible contains olmesartan medoxomil 10mg and luteolin 20-200mg.Again further preferably, wherein per unit solid orally ingestible contains olmesartan medoxomil 10mg and luteolin 100mg.
Found by animal experiment research, the pharmaceutical composition that above-mentioned active component is made up of olmesartan medoxomil and luteolin has significant biological activity in the systolic pressure steadily reducing SHR rat.Therefore, second object of the present invention is to provide a kind of new medical use, and the namely described compositions containing olmesartan medoxomil and luteolin is preparing the application for the treatment of in hypertensive medicine.
Pharmaceutical composition of the present invention treat hyperpietic time, it is crucial that luteolin needs low dosage administration as one of active component.Show that rat given low every day of each compound recipe is respectively by test: olmesartan medoxomil/luteolin compound recipe: olmesartan medoxomil 1mgkg
-1d
-, luteolin 2-20mgkg
-1d
-.
Compared with prior art, the compound medicine that the present invention relates to has following outstanding substantive distinguishing features and significant progress:
(1) concertedness treatment hypertension.Over the course for the treatment of, the medicine merging application mechanism of action different often can strengthen therapeutic effect, look after the different links in hypertension incidence mechanism simultaneously, Other Risk Factors or cohesive disease is made to obtain Optimal Control, more be conducive to the protection of target organs of patients with essential hypertension 26S Proteasome Structure and Function, reduce the incidence rate of cardiovascular event further; Zoopery shows, adopt the luteolin coupling olmesartan medoxomil of low dosage slowly and reposefully can reduce the blood pressure of rat, this is conducive to the interdependence of patient medication.
(2) untoward reaction of medicine is reduced.When reaching identical treatment effect, two class drug combinations greatly reduce the using dosage of often kind of medicine, especially reduce the using dosage of luteolin, and this just significantly reduces the untoward reaction of olmesartan medoxomil and luteolin.
(3) due to when forming immobilised compound, the dosage of each single medicine all has minimizing, and especially the dosage of luteolin significantly reduces, therefore produce and packing cost reduction, medical expense not only can not increase, and has decline on the contrary, and the benefit/expense ratio for the treatment of is significantly improved.Therefore the curative compliance of patient increases greatly, and quality of life also just obviously improves.
Detailed description of the invention
Form below by way of animal experiment example is described in further detail foregoing of the present invention again, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
embodiment 1 olmesartan medoxomil and luteolin coupling are to the effectiveness study of Hypertensive Rats
SHH rat in 8 week age (SHR) totally 40, purchased from Shanghai Slac Experimental Animal Co., Ltd..Be divided into model control group, luteolin group, Olmesartan group, drug combination group at random by body weight, amount to 4 groups, often organize 10.Luteolin, the appropriate purified water of olmesartan medoxomil are made into medicinal liquid, and the equal gastric infusion of each group rat, continues 10 weeks, and dosage is as follows respectively:
Model control group: same volume purified water;
Luteolin group: 10mg/(kg d) luteolin;
Olmesartan group: 1mg/(kg d) olmesartan medoxomil;
Drug combination group: 10mg/(kg d) luteolin+1mg/(kg d) olmesartan medoxomil.
Carried out a tail systolic arterial pressure respectively to measure at the 2nd, 4,6,8 week, the result of test data after statistics shows, luteolin does not almost show the biological activity of blood pressure lowering, and olmesartan medoxomil has antihypertensive activity fast at the medication initial stage, but in administration blood pressure bounce-back after 4 weeks.And the drug combination group of luteolin and olmesartan medoxomil, the blood pressure passing in time of its rat slowly declines stably, all have with each single medicine group after administration 4 weeks pole significant difference (
p< 0.01).
Table 1 respectively group SHR rat systolic pressure compares (kPa)
| Group | 2 weekends | 4 weekends | 6 weekends | 8 weekends |
| Model control group | 18.04±2.0 | 19.23±1.2 | 19.59±1.5 | 20.26±1.6 |
| Luteolin group | 18.10±1.8 | 18.96±1.5 | 19.02±1.8 | 19.34±2.0 |
| Olmesartan group | 16.57±2.2 ▼ | 16.91±2.1 ▼ | 18.24±2.5 | 18.83±2.7 |
| Drug combination group | 17.19±1.4 | 15.88±1.6 ▼▼● | 15.30±1.2 ▼▼★●● | 14.06±0.9 ▼▼★★●● |
▼compare with model control group,
p< 0.05,
▼ ▼compare with model control group,
p< 0.01;
★compare with olmesartan medoxomil group,
p< 0.05,
★ ★compare with olmesartan medoxomil group,
p< 0.01;
●compare with luteolin group,
p< 0.05,
● ●compare with luteolin group,
p< 0.01.
Claims (7)
1. the pharmaceutical composition containing luteolin, this pharmaceutical composition is prepared from by active component and pharmaceutic adjuvant, it is characterized in that: described active component is made up of olmesartan medoxomil and luteolin, the weight ratio of olmesartan medoxomil and luteolin is 1:2-20.
2. pharmaceutical composition according to claim 1, is characterized in that: the weight ratio of olmesartan medoxomil and luteolin is 1:5-10.
3. pharmaceutical composition according to claim 2, is characterized in that: the weight ratio of olmesartan medoxomil and luteolin is 1:10.
4. pharmaceutical composition according to claim 1, is characterized in that: described pharmaceutical composition is solid orally ingestible.
5. pharmaceutical composition according to claim 4, is characterized in that: per unit solid orally ingestible contains olmesartan medoxomil 10mg and luteolin 20-200mg.
6. pharmaceutical composition according to claim 5, is characterized in that: per unit solid orally ingestible contains olmesartan medoxomil 10mg and luteolin 100mg.
7. the application of the pharmaceutical composition described in any one of claim 1-3 in the hypertensive medicine of preparation treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410137572.4A CN103933034B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application containing luteolin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410137572.4A CN103933034B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application containing luteolin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103933034A CN103933034A (en) | 2014-07-23 |
| CN103933034B true CN103933034B (en) | 2015-11-18 |
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|---|---|---|---|
| CN201410137572.4A Expired - Fee Related CN103933034B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application containing luteolin |
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| Country | Link |
|---|---|
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130184227A1 (en) * | 2004-09-24 | 2013-07-18 | Oliver Yoa-Pu Hu | Cytochrome P450 2C9 Inhibitors |
-
2014
- 2014-04-08 CN CN201410137572.4A patent/CN103933034B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130184227A1 (en) * | 2004-09-24 | 2013-07-18 | Oliver Yoa-Pu Hu | Cytochrome P450 2C9 Inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| 木犀草素抑制AngiotensinⅡ诱导的心肌细胞肥大;杜小燕等;《科学技术与工程》;20101130;第10卷(第32期);第8790-7893页 * |
| 沙坦类药物代谢酶CYP2C9和受体AT1基因的遗传多态性在高血压患者中的分布特征;杨天伦等;《中南药学》;20070228;第5卷(第1期);第6-9页 * |
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| Publication number | Publication date |
|---|---|
| CN103933034A (en) | 2014-07-23 |
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| C41 | Transfer of patent application or patent right or utility model | ||
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Inventor after: Chen Jinjie Inventor before: Yu Fazhou |
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| TA01 | Transfer of patent application right |
Effective date of registration: 20150928 Address after: 230071 Hefei Province, Luyang District, West Road, No. 1018, crystal garden, room 3, building 206, room Applicant after: Chen Jinjie Address before: 235000 Anhui Province Economic Development Zone Huaibei City Duji District Tengfei Road No. 7 Applicant before: Yu Fazhou |
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