CN104257676B - One kind treats the migrainous compositionss of asthenic cold type - Google Patents
One kind treats the migrainous compositionss of asthenic cold type Download PDFInfo
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- CN104257676B CN104257676B CN201410545415.7A CN201410545415A CN104257676B CN 104257676 B CN104257676 B CN 104257676B CN 201410545415 A CN201410545415 A CN 201410545415A CN 104257676 B CN104257676 B CN 104257676B
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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Abstract
One kind treats the migrainous compositionss of asthenic cold type, consists of the following composition：3.0～4.0 weight portion ginsenoside Rb1With 1.0 weight portion rutaecarpins.Preferably：3.0～4.0 weight portion ginsenoside Rb1；1.0 weight portion rutaecarpins；0.15～0.60 weight portion evodine；0.50～2.0 weight portion obaculactone.More preferably：3.0～4.0 weight portion ginsenoside Rb1；1.0 weight portion rutaecarpins；0.15～0.60 weight portion evodine；0.50～2.0 weight portion obaculactone；0.60～4.0 weight portion ginsenoside Rg1；0.02～0.25 weight portion rutaecarpine.The invention provides to treating the effective neccessary composition Rb of asthenic cold type migraine1And Ev, and compatible combination Rg on this basis1, Rv, Li, Ru principle active component, it is determined that there is the compositionss of optimum curative effect to asthenic cold type migraine.
Description
Technical field
The present invention relates to one kind treats the migrainous medicine of asthenic cold type, and in particular to one kind treat asthenic cold type it is migrainous in
Pharmaceutically active ingredient compositionss.
Background technology
Migraine is a kind of multifactorial primary headache disease, to have a headache as cardinal symptom, is characterized in unilateral, violent
Throbbing pain.Calendar year 2001, migraine was classified as one of chronic disease for most disabling for World Health Organization (WHO).However, at present to migraine
Diagnosis and treat still undesirable, migrainous high incidence, high crippling, high rate of missed diagnosis, the epidemiology " three of low control rate
High one is low " feature, promote us to be necessary to find significantly more efficient migraine treatment medicine.At present, clinically migraine it is many with
Opioid drug, triptan medicine, corticosteroidss medicine, nonsteroidal antiinflammatory drug or antiepileptic are medicine, but
The application of these medicines can cause various side effect such as drug dependence, therefore the migrainous research for the treatment of by Chinese herbs by more next
More concerns.
Fructus Evodiae decoction begins to be loaded in《Treatise on Febrile Diseases》, full side is made up of Fructus Evodiae, Rhizoma Zingiberis Recenss, Radix Ginseng and Fructus Jujubae, is that ancient Chinese medicine doctor is controlled
Effective prescription of " headache due to JUE YIN disorder " is treated, is mainly used in treating various headaches on modern clinic, as which can also treat migraine
Main and disease-vomiting, therefore the migrainous effect of its treatment is taken seriously with mechanism.The functional component of further investigation Fructus Evodiae decoction
And optimum proportioning is significant for improving the curative effect of medication of traditional prescription, developing the migrainous newtype drug for the treatment of.
The content of the invention
The researcher of the present invention have found head inclined to asthenic cold type through chemical composition and whole animal pharmacodynamicss association study
Bitterly medicative Effective Component of Chinese Medicine, and determine its effective ratio range and optimum proportioning scope, so as to provide one kind
Compositionss comprising the properly mixed effective ingredient.
For achieving the above object, the present invention includes following technical scheme：
One kind treats the migrainous compositionss of asthenic cold type, and which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；With
The rutaecarpin of (b) 1.0 weight portion.
One kind treats the migrainous compositionss of asthenic cold type, and which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；
The rutaecarpin of (b) 1.0 weight portion；
The evodine of (c) 0.15～0.60 weight portion；With
The obaculactone of (d) 0.50～2.0 weight portion.
One kind treats the migrainous compositionss of asthenic cold type, and which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；
The rutaecarpin of (b) 1.0 weight portion；
The evodine of (c) 0.15～0.60 weight portion；
The obaculactone of (d) 0.50～2.0 weight portion；
The ginsenoside Rg of (e) 0.60～4.0 weight portion1；With
The rutaecarpine of (f) 0.02～0.25 weight portion.
One kind treats the migrainous medicine of asthenic cold type, and which is made up of compositionss as above and pharmaceutic adjuvant.
Medicine as above, it is preferable that the dosage form of the medicine is tablet, oral cavity disintegration tablet, injection, freeze-dried powder
Agent, granule, capsule, drop pill, pill, electuary, powder, suspensoid or oral liquid.
Medicine as above, it is preferable that described dosage form is oral liquid.
On the other hand, the present invention provides compositionss as above and is preparing prevention or treating answering in migrainous medicine
With.
The beneficial effects of the present invention is：Present invention determine that Fructus Evodiae decoction preparation is effective to treating asthenic cold type migraine
Necessary component and its optimum proportioning, i.e. ginsenoside Rb1: rutaecarpin=3.0～4.0: 1.0, most preferably ginsenoside Rb1∶
Rutaecarpin: evodine: obaculactone: ginsenoside Rg1: rutaecarpine=3.0～4.0: 1.0: 0.15～
0.60: 0.50～2.0: 0.60～4.0: 0.02～0.25, the compositionss according to made by said ratio have good treatment deficiency and coldness
The effect of type migraine disease.
Specific embodiment
Researcher of the present invention is conducted in-depth research to effective ingredient in Fructus Evodiae decoction compound recipe, has recognized Fructus Evodiae decoction system
The migrainous main component ginsenoside Rb of asthenic cold type is treated in agent1, rutaecarpin, evodine, obaculactone, Radix Ginseng
Saponin Rg1And rutaecarpine, it has further been found that neccessary composition ginsenoside Rb1With rutaecarpin, on this basis compatibility group
Close evodine, obaculactone, ginsenoside Rg1The compositionss proportioning of optimum curative effect is obtained with rutaecarpine.
Specifically, it is determined that present composition effective ingredient and optimum proportioning process are as follows：
(1) by chemical composition and whole animal pharmacodynamicss association study, have found has treatment to make to asthenic cold type migraine
Effective Component of Chinese Medicine is：Ginsenoside Rb1(Rb1), rutaecarpin (Ev), evodine (Rv), obaculactone
(Li), ginsenoside Rg1(Rg1) and rutaecarpine (Ru).
(2) using each composition components of uniform Design policy setting, compositionss one to eight (being shown in Table 1) are constituted.
Each component content (the μ gmL of 1 principle active component compositionss of table-1)
(3) pharmacodynamic index detection is carried out to each compositionss, model and detection method are set up with 1 phase of the embodiment of the present invention
Together, as a result as shown in table 2.
(4) determination of necessary component optimum proportioning
Mathematics conversion is carried out according to Hassan methods to 7 kinds of pharmacodynamics index data of each compositionss in table 2 and seeks normalizing value, subsequently
Normalizing value summation to 7 kinds of pharmacodynamics indexs in same compositionss, to open n powers (n=pharmacodynamics index numbers) and obtain final product each compositionss
Corresponding drug effect overall desirability, carries out quadratic polynomial stepwise regression analysiss using 19.0 statistical softwares of IBM SPSS, to returning
Equation is returned to carry out F inspections and variance analyses, level of significance α=0.05, P ＜ 0.05 think that equation has significance.Must return
Equation：
Y=0.982X3 2-0.244X2 2+0.516X2+0.924
X in formula2Represent ginsenoside Rb1Content, X3Represent the content of rutaecarpin.The correlation coefficient r of equation=
0.933, show that the fitting effect of equation is preferable.It is computed：X2=1.0574, X3When=0.3125, equation is in this test content
In the range of obtain maximum, now Y=1.2927.I.e. in ginsenoside Rb1Content ratio with rutaecarpin is 1057.4:
When 312.5, there is preferable therapeutic effect to asthenic cold type migraine.
(5) the Jing tests of pesticide effectiveness confirm ginsenoside Rb1When content ratio with rutaecarpin is 1057.4: 312.5, to deficiency and coldness
Type migraine has preferable therapeutic effect, and its curative effect is apparently higher than Fructus Evodiae decoction.Experimental result is referring to the embodiment of the present invention 1.
(6) research of key component optimum proportioning
In control ginsenoside Rb1: rutaecarpin=3.0～4.0: on the basis of 1.0, allotment evodine, Wu Zhu
Cornel lactone, ginsenoside Rg1With the content of rutaecarpine, curative effect more preferably compositionss proportioning is obtained.
Thus, compositionss of the present invention are obtained.Which contains the ginsenoside Rb of (a) 3.0～4.0 weight portion1；
The rutaecarpin of (b) 1.0 weight portion.Preferably：The ginsenoside Rb of (a) 3.0～4.0 weight portion1；(b) 1.0 weight portion
Rutaecarpin；The evodine of (c) 0.15～0.60 weight portion；The obaculactone of (d) 0.50～2.0 weight portion.It is more excellent
Choosing be：The ginsenoside Rb of (a) 3.0～4.0 weight portion1；The rutaecarpin of (b) 1.0 weight portion；(c) 0.15～0.60 weight
The evodine of amount part；The obaculactone of (d) 0.50～2.0 weight portion；The ginsenoside of (e) 0.60～4.0 weight portion
Rg1；The rutaecarpine of (f) 0.02～0.25 weight portion.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the present invention.The test method of unreceipted actual conditions in the following example, generally according to medicament book
Or the condition described in pharmacopeia, or according to normal condition, unless otherwise indicated, otherwise percentage ratio and number are calculated by weight.
Embodiment 1
(1) the migrainous compositionss for the treatment of asthenic cold type are prepared
Content according to table 3 prepares the migrainous compositionss for the treatment of asthenic cold type one to six.
The each component raw material of the present composition can be bought by commercial sources or adopt conventional high-performance liquid chromatography
From separation and Extraction in Radix Ginseng and Fructus Evodiae.In the present embodiment, evodine is carried from Fructus Evodiae using high performance liquid chromatography
Take, method is referring to [Li Li, Jia Ying, Chen Xiaohui wait .HPLC methods while evodine and limonin in determining Fructus Evodiae
Content (English) [J]. Chinese natural drug, 2003,1 (3)：31-33], remaining each component is commercial sources purchase.
Each component content (μ gmL of 3 each compositionss of table-1)
(2) foundation of asthenic cold type Nerve in Migraine Model
Using 7～8 week old, body weight 28～32g SPF level ICR mices (limited public affairs of Beijing dimension tonneau China experimental animal technology
Department, production permit number：SCXK (capital) 2012-0001).
Packet：Mice is grouped at random by body weight, including Normal group, sham operated rats, model group, positive drug group and each group
Compound group, 14 per group.Adaptability is raised 4.Each administration group takes the mode of administration of prevention plus treatment, by 0.2mL10g-1
The daily gavage of body weight gives relative medicine 1 time, Normal group, sham operated rats, model group group daily with etc. dosage distilled water fill
Stomach, positive drug group (Sumatriptan Succinate piece) only carry out therapeutic administratp, the dosage sumatriptan such as gavage from the 6th day, test
Totally 20 days.
Modeling：6-10 days, each administration group mice press 0.125mgkg-1Body weight subcutaneous injection of reserpine is once；11-
Reserpine dose titration on the 13rd are 0.15mgkg-1；Mice was pressed into 450mgkg in 14th-1Body weight is numb with 3% chloral hydrate
It is liquor-saturated, skin of head is cut off, a hole is bored under bregma on the right side of 2mm, sagittal suture at 2mm, is cut tail and take autoblood, inject from drill hole
2 μ L autobloods stop blooding in cerebral cortex, depth 1mm, postoperative bone wax, and penicillin antiinflammatory sutures wound surface.Sham operated rats are only bored
Hole, does not bury autologous blood clot.Gastric infusion on the -20th was the same on 15th.
Draw materials：In the 21st day by mouse anesthesia after, heart extracting blood 0.5-1.0mL, 4 DEG C stand 2h after, 4 DEG C, 5000r
min-1Centrifugation 10min takes serum, -20 DEG C of preservations, for NO contents and NOS vitality tests.By mice euthanasia, full brain, edge are taken
Clip front end cerebral tissue at pin trace, -80 DEG C of preservations, for NO contents and NOS vitality tests, remaining cerebral tissue is kept separately use
Determine in neurotransmitter.
(3) pharmacodynamic index detection
The monoamine neurotransmitters such as 5-HT, DA, NE are detected by HPLC- electrochemical processes, by kit measurement NO contents
And NOS.Results of pharmacodynamic test is shown in Table 4.
(5) pharmacodynamics index general comment normalizing
Mathematics conversion is carried out according to Hassan methods to 7 kinds of pharmacodynamics index data of each compositionss in table 4 and seeks normalizing value, for
The more obvious pharmacodynamics index of the less improvement result of numerical value is pressed formula (1) and calculates dmin, it is more obvious for the bigger improvement result of numerical value
Pharmacodynamics index is pressed formula (2) and calculates dmax。
Formula (1)
Formula (2)
The subsequently normalizing value summation to 7 kinds of pharmacodynamics indexs in same compositionss, to open n powers (n=pharmacodynamics index numbers)
The corresponding drug effect overall desirability of each compositionss is obtained final product, 5 are shown in Table.
The pharmacodynamics index overall desirability of 5 principle active component compositionss of table
(6) result and discussion
4 statistical result showed of table, after modeling, in model group Mice brain tissues, 5-HT, NE and DA content is reduced, cerebral tissue NO
Content and cerebral tissue and the rising of serum NO level S vigor, serum NO levels reduction, These parameters and Normal group and sham operated rats phase
Statistical significance (P ＜ 0.05 or P ＜ 0.01) is respectively provided with than difference.After giving different pharmaceutical treatment, local administration group mouse brain
In tissue, 5-HT contents are significantly raised, and NO contents and NOS vigor are significantly reduced, and serum NO levels are significantly raised.Each administration group NE
And DA changes of contents is not obvious.Illustrate that each compositionss group has some improvement to the migrainous pharmacodynamics index of asthenic cold type.
5 result of table shows that the action effect of each compositionss is generally better than positive drug sumatriptan and Fructus Evodiae decoction group, and group
Compound one, two ＞ compositionss three, four ＞ compositionss five, six, i.e., Jing after composition proportion, 6 kinds of compositions are better than 4 kinds of compositions, and better than 2
Plant composition.
Claims (7)
1. one kind treats the migrainous compositionss of asthenic cold type, it is characterised in which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；With
The rutaecarpin of (b) 1.0 weight portion.
2. one kind treats the migrainous compositionss of asthenic cold type, it is characterised in which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；
The rutaecarpin of (b) 1.0 weight portion；
The evodine of (c) 0.15～0.60 weight portion；With
The obaculactone of (d) 0.50～2.0 weight portion.
3. one kind treats the migrainous compositionss of asthenic cold type, it is characterised in which comprises the following ingredients：
The ginsenoside Rb of (a) 3.0～4.0 weight portion1；
The rutaecarpin of (b) 1.0 weight portion；
The evodine of (c) 0.15～0.60 weight portion；
The obaculactone of (d) 0.50～2.0 weight portion；
The ginsenoside Rg of (e) 0.60～4.0 weight portion1；With
The rutaecarpine of (f) 0.02～0.25 weight portion.
4. one kind treats the migrainous medicine of asthenic cold type, it is characterised in which is the group by any one of claim 1-3
Compound and pharmaceutic adjuvant are made.
5. medicine as claimed in claim 4, it is characterised in that the dosage form of the medicine is tablet, injection, freeze-dried powder
Agent, granule, capsule, drop pill, pill, electuary, powder, suspensoid or oral liquid.
6. medicine as claimed in claim 5, it is characterised in that described dosage form is oral liquid.
7. the application in migrainous medicine is prevented or treated to the compositionss as any one of claim 1-3 in preparation.
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| KR101923721B1 (en) * | 2016-12-06 | 2018-11-29 | 에스지상사 주식회사 | Composition for the preventing or treating of caffeinism comprising Evodia officinalis or evodiamine |
| CN108096511A (en) * | 2018-01-24 | 2018-06-01 | 刘清 | A kind of Chinese medicine preparation and its manufacturing method of rapid recovery antimigraine |
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| 外翻肠囊吸收成分与药效相关发现吴茱萸汤改善小鼠偏头痛模型指标的有效物质;潘学强 等;《"好医生杯"中药制剂创新与发展论坛论文集（下）》;20131026;816-823 * |
| 外翻肠囊吸收成分与药效相关研究吴茱萸汤治疗偏头痛的药效物质;潘学强等;《中国中药杂志》;20140131;第39卷(第1期);126-133 * |
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