CN105012441A - Application of uncaria active alkaloid to preparation of prostate medicaments - Google Patents
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- CN105012441A CN105012441A CN201510394917.9A CN201510394917A CN105012441A CN 105012441 A CN105012441 A CN 105012441A CN 201510394917 A CN201510394917 A CN 201510394917A CN 105012441 A CN105012441 A CN 105012441A
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Abstract
The present invention discloses application of uncaria active alkaloid to the preparation of prostate medicaments. Four active alkaloids (rhynchophylline, isorhynchophylline, isocorynoxeine and corynoxeine) extracted from the root of uncaria have the effect of relaxation of prostate tissues. An in vitro prostate tension tracing technology is employed for investigating the relaxant effect of the four uncaria active alkaloids on in vitro rabbit prostate and the antagonistic action of the four uncaria active alkaloids on PE (phenylephrine) and NE (norepinephrine) induced prostate shrinkage of in vitro rabbit. The study results show that rhynchophylline, isorhynchophylline, isocorynoxeine and corynoxeine can effectively diastole in vitro rabbit prostate and antagonize PE (phenylephrine) and NE (norepinephrine hormone) induced in vitro prostate shrinkage, and indicate that these four uncaria active alkaloids have potentials for the preparation of drugs for the treatment of prostatic hyperplasia.
Description
Technical field
The invention belongs to compound pharmacological action field, relate to the pharmacological action of Ramulus Uncariae Cum Uncis active alkaloid, be specifically related to Ramulus Uncariae Cum Uncis active alkaloid and preparing the application in medicine for prostate disease.
Background technology
Benign prostatic hyperplasia (benign prostatic hyperplasia, BPH) prostate hyperplasia is called for short, be a kind of common male urinary system disease, the multiple middle-aging male being born in more than 50 years old, its feature is the hypertrophy of prostate gland, smooth muscle and fibrous tissue.The clinical common prostate increase of BPH, paruria and urinary tract obstruction.These serious symptoms affect the quality of life of this middle-aging male, and along with the increase of the aged, its sickness rate is in the trend risen year by year, and therefore the treatment of BPH more and more receives the concern of people.The main purpose of Drug therapy is specific lax prostate smooth musculature cells and the prostate volume reducing hypertrophy.α
1-adrenoceptor (α
1-AR) be distributed widely in lower urethra, wherein α
1Areceptor is the Main Subtype regulating the smooth muscle such as neck of bladder, prostate, accounts for prostate α
1about 75% of-AR.Therefore, block α 1A receptor and can to relax prostate and urethral smooth muscle, improve the symptom such as BPH and lower urinary tract obstruction.Research α
1Areceptor selective antagonists is one of hot research content for the treatment of BPH, develops the α with high selectivity
1A-AR blocker or lead compound are developed significant to the drug candidate of BPH.
Summary of the invention
The object of the present invention is to provide Ramulus Uncariae Cum Uncis active alkaloid preparing the application in medicine for prostate disease, find that Ramulus Uncariae Cum Uncis active alkaloid can be used in preparing medicine for prostate disease.
For achieving the above object, the technical solution used in the present invention is:
Ramulus Uncariae Cum Uncis active alkaloid is preparing the application in medicine for prostate disease.
Described Ramulus Uncariae Cum Uncis active alkaloid is Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine or corynoxeine.
Described medicine for prostate disease is the medicine being used for the treatment of benign prostatic hyperplasia.
Described medicine for prostate disease is the medicine with diastole prostata tissue function.
Described medicine for prostate disease is shrink the medicine with antagonism for the prostata tissue caused by phenylephrine and norepinephrine.
Described medicine for prostate disease is for acting on α
1Athe medicine of-AR.
Relative to prior art, beneficial effect of the present invention is:
The invention discloses Ramulus Uncariae Cum Uncis active alkaloid and preparing the application in medicine for prostate disease, find that Ramulus Uncariae Cum Uncis active alkaloid can be used in preparing medicine for prostate disease.
Further, in the present invention, said Ramulus Uncariae Cum Uncis active alkaloid refers to the extract Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and the corynoxeine that obtain from Chinese medicine Radix Uncariae rhynchophyllae portion, finds that these four kinds of Ramulus Uncariae Cum Uncis active alkaloids are to α
1A-AR has good affinity interaction, and has the action effect of similar Tamsulosin.The present invention uses in vitro pharmacological experiment, with isolated rabbit prostate model, the prostatic effect of this four kinds of Ramulus Uncariae Cum Uncis active alkaloids diastole is verified, find that these four kinds of Ramulus Uncariae Cum Uncis active alkaloids can effective diastole Resected prostate tissue, and the contraction of Resected prostate tissue that antagonism is caused by PE (phenylephrine) and NE (norepinephrine).Illustrate that these four kinds of Ramulus Uncariae Cum Uncis active alkaloids can be used in preparing the medicine with the effect of diastole prostate, the prostata tissue that PE (phenylephrine) and NE (norepinephrine) is caused shrink there is antagonism medicine, act on α
1Athe medicine of-AR and be used for the treatment of the medicine of benign prostatic hyperplasia.
Accompanying drawing explanation
Fig. 1 is Ramulus Uncariae cum Uncis alkali and the diastole amount effect curve figure of isorhynchophylline on isolated rabbit prostate, with Tamsulosin medicine in contrast.Wherein A is the diastole amount effect curve of Ramulus Uncariae cum Uncis alkali, and B is the diastole amount effect curve of isorhynchophylline.
Fig. 2 is isocorynoxeine and the diastole amount effect curve figure of corynoxeine on isolated rabbit prostata tissue, with Tamsulosin medicine in contrast.Wherein C is the diastole amount effect curve of isocorynoxeine, and D is the diastole amount effect curve of corynoxeine.
Fig. 3 is the antagonism amount effect curve figure that Ramulus Uncariae cum Uncis alkali shrinks the isolated rabbit prostate that PE (phenylephrine) causes, wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist Ramulus Uncariae cum Uncis alkali exists, and B is Ariens noncompetitive antagonism figure.
Fig. 4 is the antagonism amount effect curve figure that isorhynchophylline shrinks the isolated rabbit prostate that PE (phenylephrine) causes, wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isorhynchophylline exists, and B is Ariens noncompetitive antagonism figure.
Fig. 5 is the antagonism amount effect curve figure that isocorynoxeine shrinks the isolated rabbit prostate that PE (phenylephrine) causes, wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isocorynoxeine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 6 is the antagonism amount effect curve figure that corynoxeine shrinks the isolated rabbit prostate that PE (phenylephrine) causes, wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist corynoxeine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 7 is the antagonism amount effect curve figure that Ramulus Uncariae cum Uncis alkali shrinks the isolated rabbit prostate that NE (norepinephrine) causes, wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist Ramulus Uncariae cum Uncis alkali exists, and B is Ariens noncompetitive antagonism figure.
Fig. 8 is the antagonism amount effect curve figure that isorhynchophylline shrinks the isolated rabbit prostate that NE (norepinephrine) causes, wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isorhynchophylline exists, and B is Ariens noncompetitive antagonism figure.
Fig. 9 is the antagonism amount effect curve figure that isocorynoxeine shrinks the isolated rabbit prostate that NE (norepinephrine) causes, wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isocorynoxeine exists, and B is Ariens noncompetitive antagonism figure.
Figure 10 is the antagonism amount effect curve figure that corynoxeine shrinks the isolated rabbit prostate that NE (norepinephrine) causes, wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist corynoxeine exists, and B is Ariens noncompetitive antagonism figure.
Detailed description of the invention
Below in conjunction with experiment and accompanying drawing the present invention is further elaborated.
Ramulus Uncariae cum Uncis alkali, isorhynchophylline, corynoxeine and isocorynoxeine are the active alkaloids of extraction and isolation from Chinese medicine Radix Uncariae rhynchophyllae portion.Pass through α
1A-AR high expressing cell membrane chromatography (CMC) screening finds, this four kinds of Ramulus Uncariae Cum Uncis active alkaloids and α
1A-AR has good affinity, and has the effect of similar Tamsulosin.Therefore, according to itself and α
1Athe affinity interaction of-AR, applicant uses in vitro pharmacological experiment, tension force is adopted to trace technology, investigate their diastole effect and the antagonism to the isolated rabbit prostata tissue contraction that PE (phenylephrine) and NE (norepinephrine) causes with rabbit Resected prostate model, and calculate its pEC
50value (medium effective concentration), and pA
2'.Result of study shows: four kinds of active alkaloids (Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine) can effective diastole rabbit Resected prostate tissue, and antagonism is by the contraction of the rabbit Resected prostate tissue going PE (phenylephrine) and NE (norepinephrine) to cause, illustrate that these four kinds of Ramulus Uncariae Cum Uncis active alkaloids are medicines of potential preparation treatment prostatic hyperplasia.
Below concrete experimentation is described.
1. experiment material
Instrument: DMT antiotasis measuring system (Danish Myograph Technology AIS Inc.610M).
Animal: male and healthy new zealand white rabbit (body weight 2.5-3.5kg, Xi'an Communications University's medical board Experimental Animal Center)
Main agents: Kerb ' s buffer solution Krebs liquid (composition (g/L): 6.954NaCl, 0.343KCl, 1.260NaHCO
3, 0.187NaH
2pO
42H
2o, 0.166CaCl
2, 0.244MgCl
26H
2o, 1.090 glucose, pH=7.2 ~ 7.4), dimethyl sulfoxide (DMSO, Jinhuada Chemical Agent Co., Ltd., Guangzhou City), noradrenaline bitartrate (NorepinephrineBitartrate Monohydrate, NE, Dalian Mei Lun Bioisystech Co., Ltd); Phenylephrine hydrochloride ((R)-(-)-Phenylephrine hydrochloride, PE, Shanghai Aladdin Reagent Company); Tamsulosin hydrochloride (HPLC purity >98%, Wuhan Chi Fei Chemical Co., Ltd.).
2. experimental technique
(1) diastole effect experiment
Get healthy Male New Zealand White Rabbit, after chloral hydrate anesthesia, hypogastric region otch, page about prostate is carefully cut along urethra, put into the surface plate of Kerb ' the s buffer solution filling pre-cooling, remove blood stains, the fatty tissue that careful rejecting is unnecessary and connective tissue, prostata tissue after separation is trimmed to the musculus prostaticus bar of about 1cm × 2mm × 2mm, be connected with DMT antiotasis measuring system with fine rule, and on computer screen, show the change of musculus prostaticus bar tension force by signal converter.Add Kerb ' s buffer solution in DMT bath, pass into containing 95%O simultaneously
2and 5%CO
2mist, maintain the temperature at 37 DEG C.After zeroing no longer includes larger change to musculus prostaticus bar tension force, give musculus prostaticus bar 4mN pretension, regulate in 20min and stablize to pretension for 3 ~ 4 times.After tension stability, make musculus prostaticus bar at 37 DEG C, 95%O
2, 5%CO
260 ~ 90min (whole experimental session changes a Kerb ' s liquid every 20min) is balanced in saturated Kerb ' s liquid.
In order to detect musculus prostaticus bar in the reactivity of in vitro to medicine, before the formal experiment of beginning, with the K of 60mmol/L
+-Kerb ' s liquid preshrinking, after its contraction reaches stabilised platform, rinses 3 times with Kerb ' s liquid, returns to after baseline values until tension force, then use the K of 60mmol/L
+-Kerb ' s liquid preshrinking, repeats said process once.If flesh bar energy stabilized contraction and twice shrink platform unanimously, prove that its function is normal, can test, abnormal flesh bar is given it up.Formal experiment is started after musculus prostaticus bar tension stability balance 20min.
After ready to balance terminates, Kerb ' s buffer in bath is settled to 10mL, after baseline stability, NE (norepinephrine) injection 50uM is added respectively successively in bath, after stable contractile response to be obtained, in bath, add the Concentraton gradient solution of Tamsulosin, Ramulus Uncariae cum Uncis alkali, isorhynchophylline, corynoxeine and isocorynoxeine more respectively successively, each concentration adds 10uL, makes the drug level in bath be followed successively by 1 × 10
-9, 3 × 10
-9, 1 × 10
-8, 3 × 10
-8, 1 × 10
-7, 3 × 10
-7, 1 × 10
-6, 3 × 10
-6, 1 × 10
-5, 3 × 10
-5, 1 × 10
-4mol/L, the tension variation of computer record musculus prostaticus bar.Matched group adds the DMSO of respective concentration gradient.With prostatic diastolic rate (%) to drug level logarithm (logC) mapping, obtain the diastole effect curve of various medicine, and calculate pEC
50.
(2) to the antagonism experiment of shrinking
Preparation method and the reactive detection of musculus prostaticus bar are the same.After ready to balance terminates, use 60mmol/L K
+-Kerb ' s buffer preshrinking, after baseline stability, rinse 3 ~ 4 times with Kerb ' s buffer solution, after tension force returns to baseline values, adopt the Concentraton gradient solution (1 × 10 adding PE (phyenlephrinium) or NE (norepinephrine) in cumulative concentrations normal direction bath
-8~ 1 × 10
-4mol/L), the concentration-shrinkage curve of two kinds of agonist is obtained.After obtaining maximum collapse effect, rinse 3 ~ 4 times, after tension force restores balance with Kerb ' s buffer solution, by alkaloid (Ramulus Uncariae cum Uncis alkali to be measured, isorhynchophylline, isocorynoxeine and corynoxeine) add bath and hatch 30min, solvent control group does not add drug incubation.And then in bath, add the Concentraton gradient solution (1 × 10 of PE (phenylephrine) or NE (norepinephrine)
-8~ 1 × 10
-4mol/L), obtain second time concentration-shrinkage curve, obtain the antagonism curve that four kinds of Ramulus Uncariae Cum Uncis active alkaloids shrink the Resected prostate that PE (phenylephrine) and NE (norepinephrine) causes.With prostatic shrinkage factor (%), the log concentration (logC) of PE (phenylephrine) and NE (norepinephrine) is mapped, namely obtain often kind of alkaloidal antagonistic effect curve, and calculate pA
2' value.
3. experimental result
Data mean ± standard error (mean ± SEM) represents, graph making application Graphpad Prism 5.0 software.
(1) Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine pEC
50as shown in table 1, diastole effect curve as depicted in figs. 1 and 2.
Table 15 kinds of medicines are to the pEC of Resected prostate diastole
50value (n=6)
| Medicine name | Tamsulosin hydrochloride | Ramulus Uncariae cum Uncis alkali | Isorhynchophylline | Isocorynoxeine | Corynoxeine |
| pEC 50 | 7.92±0.11 | 5.29±0.23 | 5.69±0.24 | 5.48±0.37 | 5.36±0.06 |
Fig. 1 and Fig. 2 is that four kinds of Ramulus Uncariae Cum Uncis active alkaloids organize the comparison (n=6) of diastole effect curve, with Tamsulosin medicine in contrast to rabbit Resected prostate.Wherein A is that Ramulus Uncariae cum Uncis alkali compares with Tamsulosin, and B is isorhynchophylline and the comparing of Tamsulosin, and C is isocorynoxeine and the comparing of Tamsulosin, and D is corynoxeine and the comparing of Tamsulosin.
(2) to the antagonism of the Resected prostate tissue contracts caused by PE (phenylephrine) as seen in figures 3-6, pA2 ' value is as shown in table 2 for Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine.
Can find out that four kinds of Ramulus Uncariae Cum Uncis active alkaloids are non-competitive antagonism to the contraction antagonism that PE (phenylephrine) causes by Fig. 3-6, general expression with pA2 ' can make the ceiling effect of agonist reduce a half, the negative logarithm of the molar concentration of non-competing antagonist.Its computational process is Ariens noncompetitive antaganist effect formula:
E
AB＝E
A×[1/(1+[B]/K
B)] ①
E
aand E
aBbe respectively the ceiling effect adding agonist before and after Antagonist concentration [B], K
bfor the dissociation constant after antagonist and receptors bind.
[E
A]/[E
AB]＝1+[B]/K
B②
Make [E
a]/[E
aB] be R, equal sign both sides are with taking the logarithm, and 2. formula becomes:
Log(R-1)＝-(-log[B])+(-logK
B) ③
With log (R-1) for Y ,-log [B] are for X, 3. publicity can be the form of linear equation Y=a+bX.PA2 '=-log [B]=-a/b as R=2.PA
2' illustrate the size of non-competitive antagonism.
Table 2: the non-competitive antagonism that four kinds of alkaloids shrink the Resected prostate that PE causes
| Medicine name | Ramulus Uncariae cum Uncis alkali | Isorhynchophylline | Isocorynoxeine | Corynoxeine |
| pA 2’ | 6.36 | 6.78 | 4.75 | 6.45 |
Fig. 3 is the non-competitive antagonism of Ramulus Uncariae cum Uncis alkali to the Resected prostate tissue contracts that PE (phenylephrine) causes.A:PE (phenylephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist Ramulus Uncariae cum Uncis alkali exists.B:Ariens noncompetitive antagonism figure.pA
2’＝6.36。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 4 is the non-competitive antagonism that isorhynchophylline shrinks the Resected prostate that PE (phenylephrine) causes.A:PE (phenylephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist isorhynchophylline exists.B:Ariens noncompetitive antagonism figure.pA
2’＝6.78。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 5 is the non-competitive antagonism that isocorynoxeine shrinks the Resected prostate that PE (phenylephrine) causes.A:PE (phenylephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist isocorynoxeine exists.B:Ariens noncompetitive antagonism figure.pA
2’＝4.75。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 6 is the non-competitive antagonism that corynoxeine shrinks the Resected prostate that PE (phenylephrine) causes.A:PE (phenylephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist corynoxeine exists.B:Ariens noncompetitive antagonism figure.PA
2'=6.45 (vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
(3) Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine are to the antagonism of the Resected prostate contraction caused by NE (norepinephrine) as is seen in figs 7-10.Four kinds of Ramulus Uncariae Cum Uncis active alkaloids are non-competitive antagonism to the contraction antagonism that NE (norepinephrine) causes as can be seen from Figure, according to its pA of Ariens formulae discovery
2' value, as shown in table 3:
Table 3: four kinds of alkaloids are to the non-competitive antagonism of the Resected prostate tissue contracts that NA causes
| Medicine name | Ramulus Uncariae cum Uncis alkali | Isorhynchophylline | Isocorynoxeine | Corynoxeine |
| pA 2’ | 7.04 | 8.46 | 8.29 | 7.09 |
Fig. 7 is the non-competitive antagonism that Ramulus Uncariae cum Uncis alkali shrinks the Resected prostate that NE (norepinephrine) causes.A:NE (norepinephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist Ramulus Uncariae cum Uncis alkali exists.B:Ariens noncompetitive antagonism figure.pA
2’＝7.04。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 8 is the non-competitive antagonism that isorhynchophylline shrinks the Resected prostate that NE (norepinephrine) causes.A:NE (norepinephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist isorhynchophylline exists.B:Ariens noncompetitive antagonism figure.pA
2’＝8.46。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 9 is the non-competitive antagonism that isocorynoxeine shrinks the Resected prostate that NE (norepinephrine) causes.A:NE (norepinephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist isocorynoxeine exists.B:Ariens noncompetitive antagonism figure.pA
2’＝8.29。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Figure 10 is the non-competitive antagonism that corynoxeine shrinks the Resected prostate that NE (norepinephrine) causes.A:NE (norepinephrine) shrinks the prostatic amount effect curve of isolated rabbit under noncompetitive antaganist corynoxeine exists.B:Ariens noncompetitive antagonism figure.pA
2’＝7.09。(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
4. conclusion
Shown by above-mentioned experimental result, Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine can effective diastole isolated rabbit prostata tissues, in addition, these four kinds of active alkaloids can also play non-competitive antagonism to the contraction of the Resected prostate that PE (phenylephrine) and NE (norepinephrine) causes.
Comprehensive above experiment can draw, present invention finds the new pharmacological action of Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine and corynoxeine, namely it has good diastole Resected prostate function, open up the clinical practice field that Chinese medicine Ramulus Uncariae Cum Uncis is new, significant to exploitation treatment BPH medicine.
Claims (6)
1. Ramulus Uncariae Cum Uncis active alkaloid is preparing the application in medicine for prostate disease.
2. apply as claimed in claim 1, it is characterized in that: described Ramulus Uncariae Cum Uncis active alkaloid is Ramulus Uncariae cum Uncis alkali, isorhynchophylline, isocorynoxeine or corynoxeine.
3. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is the medicine being used for the treatment of benign prostatic hyperplasia.
4. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is the medicine with diastole prostata tissue function.
5. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is shrink the medicine with antagonism for the prostata tissue caused by phenylephrine and norepinephrine.
6. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is for acting on α
1Athe medicine of-AR.
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|---|---|---|---|
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101036713A (en) * | 2006-03-16 | 2007-09-19 | 张文艳 | Shumitong concentrated pill and the method for preparing the same |
| CN103127105A (en) * | 2011-11-28 | 2013-06-05 | 中国药科大学 | Rhynchophylline application in drug preparing for preventing inflammation caused by excessive activation of astrocytes |
-
2015
- 2015-07-07 CN CN201510394917.9A patent/CN105012441A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101036713A (en) * | 2006-03-16 | 2007-09-19 | 张文艳 | Shumitong concentrated pill and the method for preparing the same |
| CN103127105A (en) * | 2011-11-28 | 2013-06-05 | 中国药科大学 | Rhynchophylline application in drug preparing for preventing inflammation caused by excessive activation of astrocytes |
Non-Patent Citations (1)
| Title |
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| 王嗣岑，杨芳芳: "钩藤中作用于_1A_受体的活性组分筛选分析", 《2013年中国化学会产学研合作研讨会会议论文集》 * |
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