CN104127426B - Flap Lobed Actinostemma Herb glycosides E is as the application of preparation treatment antiarrhythmic medicament - Google Patents
Flap Lobed Actinostemma Herb glycosides E is as the application of preparation treatment antiarrhythmic medicament Download PDFInfo
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- CN104127426B CN104127426B CN201410297945.4A CN201410297945A CN104127426B CN 104127426 B CN104127426 B CN 104127426B CN 201410297945 A CN201410297945 A CN 201410297945A CN 104127426 B CN104127426 B CN 104127426B
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Abstract
The present invention relates to flap Lobed Actinostemma Herb glycosides E application process in preparation treatment antiarrhythmic medicament.ARR medicine is treated in application flap Lobed Actinostemma Herb glycosides E preparation, adjuvant and preparation method can be selected for any pharmaceutically acceptable form, dosage can change according to taking the factors such as mode, the age of patient, coincident with severity degree of condition, becoming human oral dosage form is 1-200mg/ day, adult injection dosage is 1-50mg/ day, the medicine made can substantially resist that chloroform brings out mice, epinephrine brings out rabbit, barium chloride brings out rat, Aconitine Induced rat ventricular, and effect is notable.
Description
Technical field
The present invention relates to the application process of flap Lobed Actinostemma Herb glycosides E, particularly in the application process in preparation treatment antiarrhythmic medicament.
Background technology
Flap Lobed Actinostemma Herb glycosides E(LobatosideE), belong to native compound, its molecular formula: C65H102O31, molecular weight: 1379.5.Flap Lobed Actinostemma Herb glycosides E is one of effective ingredient in cucurbitaceous plant flap Lobed Actinostemma Herb, CAS accession number: 123714-91-0.
Modern study shows, flap Lobed Actinostemma Herb glycosides E has cytotoxic activity.The half growth inhibitory concentration GI50 of A-549, SK-MEL5 and SW620 cell strain is followed successively by 0.14 μM, 0.14 μM and 0.36 μM.
Chinese medicine Lobed Actinostemma Herb, have another name called Herba Actinstemmatis Lobati, celestial sphere grass, without Pennisetum centrasiaticum Tzvel etc., for the herb of cucurbitaceous plant Lobed Actinostemma Herb (ActinostemmatenerumGriff), seed and leaf, being distributed in various places, China north and south, Korea, Japan, the Soviet Union, India, South East Asia Mainland also have distribution.Herba Actinstemmatis Lobati is cold in nature, bitter in the mouth, slightly poisonous, there is inducing diuresis to remove edema, heat-clearing and toxic substances removing, the effect dried, cure mainly oedema due to nephritis, ascites swelling, venom and infantile malnutrition from the beginning of etc. disease.
Modern study finds that Herba Actinstemmatis Lobati contains the very significant saponin component of a lot of novel structure, anti-tumor activity and flavonoid, aminoacid and trace element.
Pharmaceutical research finds, Lobed Actinostemma Herb has significant anti-tumor activity, energy enhancing immunity, antithrombotic, antiinflammatory, antioxidation etc..Arrhythmia (CardiacArrhythmia) is common clinical, frequently-occurring disease, and serious arrhythmia is one of final causes of the death of patient such as myocardial hypertrophy, myocardial ischemia, myocardial infarction and heart failure.Arrhythmia refers to the exception of the frequency of cardiac impulse, the rhythm and pace of moving things, origin position, conduction velocity and exciting order.Common arrhythmia has that sinus tachycardia, sinus bradycardia, sinus rate be uneven, premature beat, paroxysmal tachycardia, atrial fibrillation, atrioventricular block etc..Clinical with cardiopalmus, palpitation with a distress feeling, abnormal pulse condition for its main manifestations, very then dizzy, dizzy, chest pain tachypnea as seen, cold extremities due to sweating or collapse.Arrhythmia belongs to the category of traditional Chinese medical science cardiopalmus card.
Cause ARR reason to have a lot, common are cardiovascular disease, electrolyte disturbance, medicine effect, infection and virus function, neural factors, endocrine factors etc..ARR electrophysiological mechanism mainly has impulsion to generate extremely, conduction of impulse is abnormal.
The traditional Chinese medical science thinks that the Etiological pathogenesis of primary disease has: timidness due to deficiency of the heart, deficiency of heart-blood, hyperactivity of fire caused by deficiency of YIN, flaccidity of the heart-yang, diseases caused by retention of fluid insult the heart, obstruction of collaterals by blood stasis etc..
Prior art not yet there is flap Lobed Actinostemma Herb glycosides E disclose as the application of preparation treatment antiarrhythmic medicament.
Summary of the invention
The technical problem to be solved in the present invention is just to provide the application process of a kind of flap Lobed Actinostemma Herb glycosides E, is namely used for preparing the ARR medicine for the treatment of.
In order to solve above-mentioned technical problem, the present invention adopts following technical proposal: flap Lobed Actinostemma Herb glycosides E is as the application of preparation treatment antiarrhythmic medicament.
Preferably, described flap Lobed Actinostemma Herb glycosides E is as sole active agent.
Preferably, described arrhythmia includes slight sinus bradycardia, arrhythmia, accidental atrial premature beat, first degree A-V block.
Preferably, described medicine can be oral or non-oral formulation.
Preferably, the dosage form of described oral formulations is the one in powder, granule, oral liquid, tablet, capsule, drop pill.
When the present invention is used for preparing treatment antiarrhythmic medicament, its oral or non-oral administration is all safely and effectively.Oral administration can make any regular dosage form, as: powder, granule, capsule, sheet, oral cavity disintegration tablet, drop pill, soft capsule etc.；Non-oral administration, can be made into various regular dosage form, such as injection etc..
When the present invention is used for preparing treatment antiarrhythmic medicament, its adjuvant and preparation method can be selected for any pharmaceutically acceptable form.
The dosage of the present invention can change according to taking the factors such as mode, the age of patient, coincident with severity degree of condition, and becoming human oral dosage form is 1-200mg/ day, and adult injection dosage is 1-50mg/ day.
When the present invention is used for preparing treatment antiarrhythmic medicament, it is possible to Western medicine or the Chinese medicine coupling with antiarrhythmic effect.
Flap Lobed Actinostemma Herb glycosides E treats ARR effect, is embodied by following test:
Test example, the flap Lobed Actinostemma Herb glycosides E impact on experimental arrhythmia animal
1, material
1.1 medicine flap Lobed Actinostemma Herb glycosides E (extract) from the herb of Lobed Actinostemma Herb ActinostemmatenerumGriff；Chloroform；Epinephrine；Barium chloride；Aconitine；Mexiletine hydrochloride, urethane.
1.2 animal Kunming mouses, body weight 30.0 ± 2.0g；The big ear rabbit of Japan, body weight 2.8 ± 0.5Kg；Wistar rat, body weight 300 ± 20g.
1.3 instrument biological functional system BL-420E(Chengdu TME Technology Co., Ltd.).
2, data process measurement data represents with x ± s, t inspection between organizing.Numeration data carries out χ 2(2 × 2) inspection.
3, test method
3.1 pairs of chloroforms bring out the effect quivered in mice room
Taking mice, male and female half and half, be randomly divided into 5 groups, often group 15, wherein normal saline group is with respective amount normal saline gavage.High dose group, middle dosage group, low dose group gavage respectively give 6.4,3.2,1.6mg/Kg flap Lobed Actinostemma Herb glycosides E；Positive controls gavage gives mexiletine hydrochloride 32.0mg/Kg.Successive administration 7 days, after last administration 30min, is respectively put into each Mus in the bell glass containing 2ml chloroform cotton balls 500ml by 1 times/day, when mouse breathing is about to stop, cuts open breast immediately and observes and occur quivering number of mice in room, and calculates each group of room and quiver occurrence rate.
3.2 pairs of epinephrines bring out rabbit Arrhythmia
Taking rabbit, male and female half and half, be randomly divided into 5 groups, often group 6, wherein normal saline group is with respective amount normal saline gavage.High dose group, middle dosage group, low dose group gavage respectively give 1.6,0.8,0.4mg/Kg flap Lobed Actinostemma Herb glycosides E；Positive controls gavage gives mexiletine hydrochloride 8.0mg/Kg.Successive administration 7 days, 1 times/day, after last administration 30min, injection urethane 1.2mg/Kg anesthesia, leads after ECG with each rabbit front II of electrocardiograph record respectively, intravenous injection epinephrine 40 μ g/Kg, 4S has injected, by showing that glass device observes the rhythm of the heart, synchronous recording ECG, during to recovery sinus rhythm completely, calculate arrhythmia time of origin and persistent period.
3.3 anti-barium chlorides bring out rat ventricular effect
Taking rat male and female half and half, be randomly divided into 5 groups, often group 10, wherein normal saline group is with respective amount normal saline gavage.High dose group, middle dosage group, low dose group gavage respectively give 3.2,1.6,0.8mg/Kg flap Lobed Actinostemma Herb glycosides E；Positive controls gavage gives mexiletine hydrochloride 16.0mg/Kg.Successive administration 7 days, 1 times/day, after last administration 30min, injection urethane 1.2mg/Kg anesthesia, leads after ECG with each rabbit front II of electrocardiograph record respectively, intravenous injection barium chloride 4mg/Kg, 4S has injected, by showing that glass device observes the rhythm of the heart, synchronous recording ECG, during to recovery sinus rhythm completely, calculate arrhythmia time of origin and persistent period.
3.4 anti-Aconitine Induced rat ventricular effects
Taking rat male and female half and half, random packet, often group 12, wherein normal saline group is with respective amount normal saline gavage.High dose group, middle dosage group, low dose group gavage respectively give 3.2,1.6,0.8mg/Kg flap Lobed Actinostemma Herb glycosides E；Positive controls gavage gives mexiletine hydrochloride 1.6 × 10-2g/Kg.Successive administration 7 days, 1 times/day, after last administration 30min, injection urethane 1.2mg/Kg anesthesia respectively, lead after ECG with each rabbit front II of electrocardiograph record, inject aconitine 0.09 μ g/min through sublingual vein constant speed, calculate arrhythmia time of origin and 1 hours survival.
4, result of the test
Chloroform is brought out the impact quivered in mice room by 4.1
Result of the test is in Table 1, it is shown that compared with normal saline group, positive controls, each dosage group of flap Lobed Actinostemma Herb glycosides E occur that the mice number quivered room significantly reduces, occurrence rate significantly reduces (P < 0.05,0.01).
Epinephrine is brought out the ARR impact of rabbit by 4.2
Result of the test is in Table 2, result shows, compared with normal saline group, positive controls, flap Lobed Actinostemma Herb glycosides E each dosage group can significantly be postponed epinephrine and be brought out the ARR time of origin of rabbit (P < 0.01), shortens the ARR persistent period (P < 0.05,0.01).
4.3 impacts that barium chloride brought out rat ventricular
Result of the test is in Table 3, result shows, compared with normal saline group, positive controls, each dosage group of flap Lobed Actinostemma Herb glycosides E can significantly be postponed barium chloride and be brought out the time of origin (P < 0.01) of rat ventricular, shortens the ARR persistent period (P < 0.05,0.01).
4.4 impacts on Aconitine Induced rat ventricular
Result of the test is in Table 4, result shows, compared with normal saline group, positive controls, each dosage group of flap Lobed Actinostemma Herb glycosides E can significantly postpone the time of origin (P < 0.05,0.01) of Aconitine Induced rat ventricular, improve 1 hours survival (P < 0.05,0.01) of Aconitine Induced arrhythmia rat.
In sum, flap Lobed Actinostemma Herb glycosides E can substantially resist that chloroform brings out mice, epinephrine brings out rabbit, barium chloride brings out rat, Aconitine Induced rat ventricular, and above-mentioned effect is the pharmacological basis of its treatment arrhythmia.
Detailed description of the invention
Embodiment 1
Tablet: flap Lobed Actinostemma Herb glycosides E10g, starch 190g, granulates, and tabletting makes 1000.Instructions of taking: be grown up one time 1,2 times on the one.
Embodiment 2
Capsule: flap Lobed Actinostemma Herb glycosides E10g, starch 190g, mixing, make 1000.Instructions of taking: be grown up one time 1,2 times on the one.
Claims (5)
1. flap Lobed Actinostemma Herb glycosides E is as the application of preparation treatment antiarrhythmic medicament.
2. flap Lobed Actinostemma Herb glycosides E treats the application of antiarrhythmic medicament as preparation according to claim 1, it is characterised in that described flap Lobed Actinostemma Herb glycosides E is as sole active agent.
3. flap Lobed Actinostemma Herb glycosides E treats the application of antiarrhythmic medicament as preparation according to claim 1, it is characterised in that described arrhythmia includes slight sinus bradycardia, arrhythmia, accidental atrial premature beat, first degree A-V block.
4. flap Lobed Actinostemma Herb glycosides E treats the application of antiarrhythmic medicament as preparation according to claim 1, it is characterised in that described medicine can be oral or non-oral formulation.
5. flap Lobed Actinostemma Herb glycosides E treats the application of antiarrhythmic medicament as preparation according to claim 4, it is characterised in that the dosage form of described oral formulations is the one in powder, granule, oral liquid, tablet, capsule, drop pill.
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Effective date of registration: 20170407 Address after: 518057 Guangdong Shenzhen high tech Zone, Shahe street, a high-tech incubator building 2-106 Patentee after: SHENZHEN FORWARD PHARMACEUTICALS Co.,Ltd. Address before: Tianhe District Tong East Road Guangzhou city Guangdong province 510665 B-101 No. 5, room B-118 Patentee before: GUANGDONG GAOHANG INTELLECTUAL PROPERTY OPERATION Co.,Ltd. Effective date of registration: 20170407 Address after: Tianhe District Tong East Road Guangzhou city Guangdong province 510665 B-101 No. 5, room B-118 Patentee after: GUANGDONG GAOHANG INTELLECTUAL PROPERTY OPERATION Co.,Ltd. Address before: No. 2 Taishan Road, Jiangsu science and Technology Park, 215000 Canton City of Suzhou province high tech Zone 2-104 Patentee before: Suzhou Paiteng Biological Medical Technology Co.,Ltd. |
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