CN1323793A - Schizonepeta lactone and its extraction process and use - Google Patents

Schizonepeta lactone and its extraction process and use Download PDF

Info

Publication number
CN1323793A
CN1323793A CN 01108186 CN01108186A CN1323793A CN 1323793 A CN1323793 A CN 1323793A CN 01108186 CN01108186 CN 01108186 CN 01108186 A CN01108186 A CN 01108186A CN 1323793 A CN1323793 A CN 1323793A
Authority
CN
China
Prior art keywords
schizonepetolactone
ethyl acetate
extract
purposes
prepare
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN 01108186
Other languages
Chinese (zh)
Other versions
CN1174973C (en
Inventor
丁安伟
张丽
丁婕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing University of Chinese Medicine
Original Assignee
Nanjing University of Chinese Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanjing University of Chinese Medicine filed Critical Nanjing University of Chinese Medicine
Priority to CNB011081864A priority Critical patent/CN1174973C/en
Publication of CN1323793A publication Critical patent/CN1323793A/en
Application granted granted Critical
Publication of CN1174973C publication Critical patent/CN1174973C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Abstract

The present invention relates to the extraction technology and application of nepetalactone, its chemical formula C10H14O3 is disclosed. Its melting point is 188-189 deg.C, and its specific optical rotation is ([a]D to the power 20)=+46.7 deg. Its can be used in the preparation of medicine for anticory virus, inflammation medicine, medicine for inhibiting streptococcus B, analgesic, sweat medicine etc..

Description

Schizonepetolactone and extraction process thereof and purposes
The present invention relates to a kind of monoterpene, specifically, relate to the Schizonepetolactone that extracts by schizonepeta, and it is as the purposes of medicine.
The monoterpenes compound is by extensive studies, also be synthesized (referring to Tetrahedron Vol.49, No.29, pp.6429-6436 as (+) different peppermint lactone, 1993), but do not have report from the medicinal material schizonepeta, to extract the monoterpene Schizonepetolactone that obtains a kind of menthane type so far.
The object of the present invention is to provide a kind of Schizonepetolactone that from the medicinal material schizonepeta, extracts and its extracting method and as the purposes of medicine.
Technical scheme of the present invention such as following.
Schizonepetolactone, its molecular formula are C 10H 14O 3, fusing point is 188-189 ℃, its specific rotatory power is [α] D 20=+46.7 ° (ethyl acetate solution), its structural formula as shown in Figure 1, the temporary called after Schizonepetolactone of the inventor (Schizonepetin).
The extracting method of Schizonepetolactone of the present invention comprises the steps:
A. the schizonepeta medicinal material is extracted with the ethanol heating, gets ethanol extract, get pure medicinal extract behind the ethanol extract decompression recycling ethanol,
B. the pure medicinal extract ethyl acetate extraction that the A step is obtained gets acetic acid ethyl ester extract with acetic acid ethyl acetate extract reclaim under reduced pressure ethyl acetate,
C. acetic acid ethyl ester extract is carried out column chromatography with chromatographic silica gel dress post, carries out gradient elution, collect stream part of containing Schizonepetolactone, leave standstill and separate out coarse-grain, be the Schizonepetolactone crude product with petroleum ether-ethyl acetate,
The Schizonepetolactone crude product with ethyl acetate-sherwood oil recrystallization, is obtained the granular crystal of Schizonepetolactone, and purity can reach more than 99%.
Concrete operation is as follows:
Get schizonepeta raw medicinal herbs medicine materical crude slice (cutting into the long segment of 0.5-1.0cm after the schizonepeta medicinal material profit) 13kg, soaking (50 ± 2 ℃) with 10 times of amounts (130kg), 95% medical ethanol temperature (was respectively 2 days for 5 times, 1 day, 1 day, 1 day, 1 day), stir 2-3 every day, filter, merge vat liquor, do not obtain pure medicinal extract to there being the alcohol flavor in 70 ℃ of decompression recycling ethanols.
Divide 2 extractions with gained alcohol medicinal extract with ethyl acetate (AR) 1500ml, each 750ml, acetic acid ethyl acetate extract concentrating under reduced pressure (60 ℃ 0.09Mpa) to doing, get acetic acid ethyl dissolution thing 430g; 500g mixes sample, dry column-packing with column chromatography silica gel (100-200 order).Silica gel is 8: 1 with the ratio of sample size; Carry out the normal pressure gradient elution with sherwood oil (60-90 ℃)-ethyl acetate, every 500ml is first-class part, and from pure sherwood oil, every 20000ml increases by 2% ethyl acetate, merge sherwood oil: ethyl acetate=100: 6-100: 8 sections stream parts, leaving standstill promptly had coarse-grain to separate out in 2-3 days.
Coarse-grain can be got granular crystal with ethyl acetate (AR)-sherwood oil recrystallization, and purity can reach 99.4% (the HPLC normalization method records); Mother liquor is concentrated, mix sample and dry method upper prop with silica gel H with thin-layer chromatography, with sherwood oil: ethyl acetate=100: 7 pressurization wash-outs, there are a large amount of coarse-grain wash-outs to go out post again, the same method is with ethyl acetate one sherwood oil recrystallization, the Schizonepetolactone crystallization that gets final product purelyr.
The pharmacological testing of Schizonepetolactone shows that it has stronger physiologically active.Test shows:
It death has significant protective effect to the influenza virus infecting mouse, and can reduce the lung index value of influenza infection mouse, therefore can be used for preparing anti-common cold virus medicine;
2. it can obviously suppress the mice ear due to the Oleum Tiglii and obviously suppress the increase that abdominal injection HAC causes the mouse capillary permeability, has tangible anti-inflammatory action, therefore can be used for preparing anti-inflammation drugs;
3. it has stronger anti-microbial effect to beta streptococcus, therefore can be used for preparing the medicine that suppresses beta streptococcus;
4. it can effectively reduce the number of times that abdominal injection chemistry algogen HAC induced mice is turned round body, can obviously improve the threshold of pain of mouse to warm stimulation again, therefore can be used for preparing analgesic agent;
It to make histamine phosphate cause the guinea pig trachea spiral groove of convulsion lax, therefore can be used to prepare Claritin;
6. it has significant excitation to rat paw portion sweat gland, therefore can be used to prepare sudorific.
Schizonepetolactone of the present invention is a kind of new menthane type monoterpenes compound, and it is simple in structure, and simple and convenient extraction is inexpensive, has stronger physiologically active.
Description of drawings:
Fig. 1 is the structure iron of Schizonepetolactone;
Fig. 2 is Schizonepetolactone high resolution mass spectrum figure;
Fig. 3 is the infrared spectrogram of Schizonepetolactone;
Fig. 4 is the Schizonepetolactone ultraviolet spectrogram;
Fig. 5 is Schizonepetolactone H 1-NMR spectrogram;
Fig. 6 is Schizonepetolactone C 13-NMR spectrogram;
Fig. 7 is a Schizonepetolactone X-ray spectrogram;
Fig. 8 is Schizonepetolactone high pressure liquid chromatography figure.
Further specify the present invention by the following examples.
Embodiment 1:
Get schizonepeta raw medicinal herbs medicine materical crude slice 6kg and (originate in Yangzhou, Jiangsu, lot number: 980911), soaked (50 ± 2 ℃) 48 hours with 95% medical ethanol temperature, the middle stirring 4-6 time, filter (earlier with the double gauze coarse filtration, again with B decompression with the smart filter of filter paper), merging filtrate, in 70 ℃ of decompressions (vacuum tightness is crossed 0.06-0.07MPa) recovery ethanol to do not have alcohol distinguish the flavor of pure medicinal extract 1; The dregs of a decoction were soaked (50 ± 2 ℃) 24 hours with 45kg95% ethanol temperature, and middle the stirring 2-3 time filtered (method is the same), merging filtrate, decompression recycling ethanol (condition is the same) and must pure medicinal extract 2; The dregs of a decoction are extracted 3 times again, and each samming soaks 24 hours (method is the same), filters, concentrate pure medicinal extract 3,4,5. Medicinal extract 1,2,3,4,5 is merged, obtain 650g medicinal extract altogether.
Pure medicinal extract 1.25kg is pinched molten 2 times each 400ml, acetic acid ethyl acetate extract concentrating under reduced pressure (60 ℃ 0.08-0.09Mpa) to doing, obtain acetic acid ethyl dissolution thing 196g with ethyl acetate 800ml; 220g mixes sample with column chromatography silica gel (100-200 order), (60 ℃ of decompression oven dry, 0.08-0.09Mpa), porphyrize, cross 80 mesh sieves, (glass column 8cm * 120cm), silica gel is 8: 1 (dress post silica gel is 1600g) with the ratio of sample size to dry column-packing, carry out the normal pressure wash-out with sherwood oil (60-90 ℃)-ethyl acetate, every 500ml is first-class part, and from pure sherwood oil, every 20000ml increases by 2% ethyl acetate, merge sherwood oil: ethyl acetate=100: 6-100: 8 sections stream parts, leaving standstill promptly had coarse-grain to separate out in solution in 3-5 days, continued to place for 4 weeks, filtered, crystallization can obtain granular crystal with the petroleum ether-ethyl acetate recrystallization, filter, drying under reduced pressure gets granular crystal 725mg, purity is 99.7% (the HPLC normalization method records 99.7%, sees Fig. 8); With mother liquor concentrate thick paste 1.6g, mix sample with silica gel H 4g (200-300 order), and the dry method upper prop (4 * 100cm), silica gel consumption 50g, with sherwood oil: ethyl acetate=100: 8 pressurization wash-outs, collect elutriant meter 6000ml (track to the whole wash-outs of lactone with TLC and go out post), and concentrating under reduced pressure (50 ℃, 0.07MPa) to 200ml, be transferred to while hot in the 250ml triangular flask, promptly there is coarse-grain to separate out after the cooling, placed for 2 weeks, solvent is volatilized naturally.Coarse-grain with the petroleum ether-ethyl acetate recrystallization, is got granular crystal 241mg, through HPLC (C 18Post, methyl alcohol: water=45: 55 is moving phase, λ=216nm, sensitivity is 2AUFS, flow velocity is 0.8ml/min) detect, gained 241mg and aforementioned 725mg crystal are same compound herein, and the two is merged common crystalline compounds 966mg, yield is 0.0161%.
Embodiment 2: the Schizonepetolactone structure elucidation:
Schizonepetolactone is a colourless grain brilliant (ethyl acetate), mp:188-189 ℃.The TLC thin layer shows red (10% sulfuric acid ethanol), the M that high resolution mass spectrum records +Be 182.0915 (Fig. 3, calculated value are 182.0941), molecular formula is C 10H 14O 3, prompting may be a monoterpenes compound.Bibliographical information separates four monoterpenes compositions that obtain and is all the menthane type from schizonepeta, from the source of students analysis, this monoterpenes compound also may be the menthane type.
Infrared spectra shows that compound has hydroxyl (3353cm -1), carbonyl (1692cm -1, 1743cm -1) and ring texture (1743cm -1) (Fig. 4); UV spectrum λ Max(log ε): 216nm (4.0842) (Fig. 5) shows that compound has conjugation and absorbs feature.
1H-NMR (CDCL 3) show that (3H, d J=2.1Hz) are the methyl that is connected on two keys to two methyl peak δ 1.8ppm; (3H, d is J=6.6Hz) for being connected in the methyl (Fig. 6) on the methyne for δ 0.97ppm.
13The C-NMR spectrum records this crystallization ten carbon (ppm): δ 172.2, δ 160.3, δ 121.3, δ 103.4, δ 46.0, δ 35.0, δ 29.1, δ 24.3, δ 21.0, δ 8.1 (Fig. 7).
In order to illustrate the absolute configuration of compound, we have made the monocrystalline X-ray analysis, and the structure of compound shows that bond distance and bond angle are based on normal scope (Fig. 8).
The cleavage of mass spectrum peak of compound is (m/z): M +182, base peak is 154 (M +-CO), main fragmention has
164,149,139,137,121,109,93,81 (Fig. 2).Embodiment 3: the antivirus test of Schizonepetolactone
(1) to the provide protection of influenza a virus infection mouse.
Get 120 of Kunming mouses, body weight 11～13g.Be divided into 6 groups at random, 20 every group, ♀ ♂ half and half.Each organizes mouse under the ether light anaesthesia, infects every mouse 30 μ l (30 LD with viral allantois drop nose 50Challenging dose).Observe zoogenetic infection sequela symptom, record infects death toll in the 15d of back.The result is as shown in table 1.Table 1 Schizonepetolactone is to H 1N 1The provide protection of virus infected mice death
Dosage number of animals death toll mortality ratio group (mg/kg) is (n) (%) X (n) 2P Normal group-20 0 virus control group-20 19 95 Ribavirin group 75 20 10 50 8.03＜0.005 nepetalactone I group 1.7 20 14 70--nepetalactone II group 5 20 12 60 5.16＜0.05 nepetalactone III group 10 20 10 50 8.03＜0.005 and virus control group comparison P＜0.05 P＜0.005
Experimental result shows, Schizonepetolactone 5mg/kg dosage group, and death has obvious provide protection to the influenza virus infecting mouse.
(2) to the influence of influenza virus Lung Index of mice infected by Influenza virus
Get 50 of Kunming mouses, body weight 12-14g is divided into 5 groups at random, ♀ ♂ half and half, 10 every group.Each treated animal ig administration, the 0.2ml/10g mouse is heavy, and 1 time/d, continuous 5d, 2d after administration, each organizes mouse under the ether light anaesthesia, infects every 30 μ l, (20 LD with viral allantois drop nose 50Challenging dose), fasting (can't help water) before the experiment, experiment was respectively organized mouse and weigh the same day, took off cervical vertebra and put to death, and dissected, and observed pulmonary lesion, got full lung and weighed, and calculated each mouse lung index value, lung index inhibiting rate, test-results sees Table 2.
Table 2 Schizonepetolactone is to H 1N 1The influence of virus infected mice lung exponential (x ± s) -Group number of animals dosage lung index value inhibiting rate
(only), (mg/kg), (%) virus control group 10-1.550-0.12 ribavirin group 10 75.0 1.039 ± 0.111* 33 Schizonepetolactone I groups 10 1.7 1.145 ± 0.32* 26 Schizonepetolactone II groups 10 5.0 1.084 ± 0.28* 30 Schizonepetolactone III groups 10 10.0 1.064 ± 0.28* 31 compares * P＜0.005 * * P＜0.001 with the virus control group
Experimental result shows: three dosage groups of Schizonepetolactone, all can reduce the lung index value of influenza infection mouse, and compare the difference highly significant with the virus control group.
Embodiment 4: the anti-inflammatory action of Schizonepetolactone
Adopt 2 kinds of inflammatory models to study the anti-inflammatory action of Schizonepetolactone.As a result Schizonepetolactone with 5.00,7.00, the 9.75mg/kg intraperitoneal injection is to the restraining effect highly significant of mouse peritoneal capillary permeability and crotons oiliness ear swelling, its high dose group is suitable with the effect of acetylsalicylic acid group.
[method and result]
Influence (auricle edema method) to the Mice Auricle inflammation: get 50 of mouse, male and female half and half, body weight 18～22g is divided into 5 groups at random.Press table 3 intraperitoneal injection respectively, only be coated with Oleum Tiglii 0.1ml/ for after 30 minutes ear two sides, a mouse left side.Cut two ears about mouse after 4 hours, punch at same position, weigh immediately, calculate the swelling degree, result such as table 3 with the 9mm punch tool.Table?3?Effect?of?Schizonepetin?on?Mice?Ear?SwellingGroup Number Dose(mg/kg) Swelling?Rate(x±S,％)Normal?Saline 10 / 182.3±4.5Aspirin 10 84.5 138.0±6.7 *SchizonepetinⅠ 10 5.00 164.1±19.9 ##SchizonepetinⅡ 10 7.00 156.0±11.8 **##SchizonepetinⅢ 10 9.75 134.1±11.4 **
SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?dose
SchizonepetinⅢ(S3):higher?dose
Vs?Normal?Saline?group? *P＜0.05? **P＜0.01
Vs?Aspirin?group? ##P＜0.01
Influence (the abdominal cavity dyestuff oozes out method) to the mouse peritoneal capillary permeability: getting body weight is 50 of 18～22g male mices, is divided into 5 groups at random, presses table 4 intraperitoneal injection respectively.The blue normal saline solution 0.1ml/10g of tail vein injection 0.5% ivens after 30 minutes, abdominal injection 0.5%HAC 0.2ml/ only immediately.Put to death mouse after 20 minutes, cut off the abdominal cavity, divide with 6ml physiological saline and wash the abdominal cavity for several times, after sucking-off, the merging, draw 2.0ml respectively and add physiological saline and be diluted to 10ml, in 3000rpm centrifugal 15 minutes, get supernatant liquor in 590nm place colorimetric, measure its OD value, organize a t check, result such as table 4.Tab4?Schizonepetin′s?Activity?on?Capillary?Pemeability?in?Mice′s?Cavum?AbdominisGroup Number Dose OD?Value(590nm)
(mg/kg) (x±S)NormalSaline 10 / 1.159±0.263Aspirin 10 84.25 0.702±0.190 **SchizonepetinⅠ 10 5.00 0.859±0.241 ##SchizonepetinⅡ 10 7.00 0.874±0.191 *#SchizonepetinⅢ 10 9.75 0.560±0.169 **SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?doseSchizonepetinⅢ(S3):higher?doseVs?Normal?Saline?group? *P＜0.05? **P＜0.01Vs?Aspirin?group? #P＜0.05? ##P＜0.01
[conclusion] above test-results shows, Schizonepetolactone can obviously suppress the increase that Oleum Tiglii induced mice ear swelling and abdominal injection HAC cause the mouse capillary permeability, with the physiological saline group relatively, difference highly significant (P＜0.05, P＜0.01), its restraining effect strengthens with dosage.
The analgesic activity of embodiment 5. Schizonepetolactones
Adopt 2 kinds of pain models to study the analgesic activity of Schizonepetolactone.As a result Schizonepetolactone with 5.00,7.00, the 9.75mg/kg intraperitoneal injection can improve the threshold of pain of mouse to warm stimulation, can reduce mouse again and turn round the body number of times what chemical algogen (HAC) stimulated, with the dolantin group relatively, its analgesic activity has the characteristics of the slow and long action time of onset.
[method and result]
Writhing method: get 50 of mouse, male and female half and half, body weight are 18～22g, are divided into 5 groups at random, press table 5 intraperitoneal injection respectively.The equal abdominal injection 0.5%HAC of each mouse 0.2ml/ only after 30 minutes.Observe respectively to organize in 10 minutes and writhing response (belly indent, stretching, extension hind leg, buttocks are raised) number of animals, result such as table 5 occur.Table 5 Effect of Schizonepetin on Chemical Schizonepetolactone imuli to MiceGroup Number Dose (mg/kg) Twi Schizonepetolactone ing
number(x±S)NormalSaline 10 / 27.6±2.6Aspirin 10 84.5 11.8±3.3 **SchizonepetinⅠ 10 5.00 24.6±5.1 ##SchizonepetinⅡ 10 7.00 16.4±3.5 **#SchizonepetinⅢ 10 9.75 9.5±1.6 **
SchizonepetinⅠ(S1):lowerdose；SchizonepetinⅡ(S2):intermediatedose
SchizonepetinⅢ(S3):higher?dose
Vs?Normal?Saline?group? **P＜0.01
Vs?Aspirin?group? #P＜0.05? ##P＜0.01
Hot plate method: regulate water bath with thermostatic control, make water temperature be controlled at 55.0 ℃ ± 0.5 ℃.Get 70 of 18～22g female mices and screen qualified mouse.Method is: mouse is placed on the hot plate, observes mouse and lick the time (second) that metapedes occurs, with this section period as the threshold of pain of this mouse (all lick the metapedes time less than 5 seconds or give it up greater than 30 seconds or leaper).Be divided into 5 groups at random through screening 50 of qualified mouse, repeat to survey its normal threshold of pain, get two subnormal threshold of pain mean values as this mouse administration before threshold of pain.Observe drug effect: each group is all by table 6 intraperitoneal injection, surveys the mouse threshold of pain after the administration in 15,30,60,90 minutes respectively.As 60 minutes still reactionless, mouse is taken out, in order to avoid scald, its threshold of pain calculated with 60 seconds, obtained the threshold of pain and improved percentage, result such as table 6.Table 6 Schizonepetin ' s Activity on Hot Plate Schizonepetolactone imuli to MiceGroup Number Dose Elaltation of Pain Threshold (X ± S)
(mg/kg) 15min 30min 60min 90minNormal?Saline 10 / -4.32+41.35 6.26+32.63 11.53+49.06 77.76+95.48SchizonepetinⅠ 10 5.00 -5.01+40.85* -3.02+35.26* 62.44+95.7* 85.04+60.3*SchizonepetinⅢ 10 7.00 3.25+20.5* -6.6+21.86* 65.28+46.51** 57.05+61.12*SchizonepetinⅢ 10 9.75 23.91+40.13* 80.87+80.0** 108.95+57.24* 102.6+56.7*Dolantin 10 50 133.67+46.8*** 106.5+96.4*** 153.4+146.1** 125.02+60.2*SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?doseSchizonepetinⅢ(S3):higher?dose
Vs?Normal?Saline?group? *P＞0.05? **P＜0.05? ***P＜0.01
Experimental result shows that Schizonepetolactone can obviously improve the threshold of pain of mouse to warm stimulation.
[conclusion] result show, Schizonepetolactone can effectively reduce the number of times that abdominal injection chemistry algogen HAC induced mice is turned round body, can obviously improve the threshold of pain of mouse to warm stimulation again; Compare difference highly significant (P＜0.05, P＜0.01) with the physiological saline group.Its effect strengthens with dosage.
The anti-allergic effects of embodiment 6. Schizonepetolactones
Schizonepetolactone is to the influence (tracheae spiral groove method) of guinea-pig isolated tracheal smooth muscle
[method] 1. the preparation and the muscular tension of tracheae spiral groove regulates: regulate water bath with thermostatic control before the experiment and make temperature be controlled at 37 ± 0.5 ℃, Magnus' bath is placed water-bath, in Magnus' bath, add the Krebs nutritive medium, pass to an amount of (keeping 1-2 bubble p.s.) pure oxygen, standby.Get the 350-400g cavy, cause death with the wooden Chui head of fiercelying attack.Cut skin of neck rapidly, separate tracheae, whole section tracheae cut down to tracheae lower end crotch from thyroid cartilage, put into the culture dish that fills nutritive medium (nutritive medium use in advance oxygen saturated), the careful tracheae reticular tissue on every side of rejecting, tracheae is cut into strip-spiral, and one section tracheae is made 2 spiral groove.Each wears single line with suture needle at tracheae spiral groove two ends, the one end is tied up on the little hook of L type ventpipe, carefully puts into Magnus' bath.Be fixed on the retort stand with the other end of concave-concave folder ventpipe.The counterweight of a heavy 2g is hung on the muscular strength transverter height that record 2g load rises pen.Take off counterweight, the other end of tracheal strip is connected on the transverter with line, regulate its tension force, make pen just be elevated to the height of 2g load, the pulling force that this moment, tracheal strip bore is 2g.
2. observation drug effect: after stablizing 30 minutes, connect registering instrument power supply [time constant (S) DC, filtering (Hz) 10, sensitivity (mV/cm) 1, chart drive speed 4mm/min], write down one section normalized curve, add histamine phosphate then, making the interior concentration of bath is 1.67 * 10 -6G/ml, when tracheal smooth muscle tension force was raised to vertex, each sample of medication group added the Schizonepetolactone suspension, and making the interior concentration of groove is 1.85 * 10 -2Mg/ml, control group add the physiological saline with volume, observe relatively curve fall after two groups of sample administrations, and by following public affairs place whizzer with centrifugal 10 minutes of 2000rpm blood plasma, with its specific viscosity of determination of plasma.The detection index is as follows:
Whole blood contrast viscosity=whole blood flow velocity (second)/NS flow velocity (second)
The whole blood contrast viscosity of low shear rate, middle shear rate and high shear rate calculates respectively.
Plasma viscosity=plasma flow rate (second)/NS flow velocity (second)
RBC hematocrit (HCT): the whole blood mixing is injected in the RBC hematocrit pipe, with 3000rpm centrifugal 30 minutes, observe RBC hematocrit pipe scale (white corpuscle partly is not counted in).
[result] Schizonepetolactone can make the rat whole blood viscosity reduce, and the RBC aggregate index is reduced, thereby blood viscosity lowering improves hemorheology.As table 10:
Table?10?Effect?of?Schizonepetin?on?Hemorrheology?of?Rats
Dose Whole?Blood?Specific?Viscosity RBCGroup Number?(mg/kg) L.T. M.T. H.T. Aggregation
(8?1/S) (60?1/S) (120?1/S) IndexNormal?Saline 10 / 15.25±2.26 7.59±1.19 5.84±0.74 2.90±0.45SchizonepetinⅠ 10 5.0 16.46±2.01 7.27±0.63 5.62±0.25 3.28±0.82SchizonepetinⅡ 10 10.0 13.69±1.48 6.78±0.32 *?4.86±0.30 **2.66±0.68SchizonepetinⅢ 10 20.0 10.9±2.04 **?6.18±1.30 *?4.80±0.85 *?3.11±0.80Pilocarpine 10 35.0 11.4±0.91 **?6.12±0.81 **4.90±0.57 *?2.50±0.23 *SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?doseSchizonepetinⅢ(S3):higher?doseVs?Normal?Saline?group? *P＜0.05? **P＜0.01
The bacteriostatic test of embodiment 9. Schizonepetolactones
[result] Schizonepetolactone soup has stronger anti-microbial effect (its MIC is 0.08mg/ml) to beta streptococcus, and not obvious to other bacterial classification antibacterial effects, sees Table 11.
Table 11 Effect?of?Schizonepetin?on?some?kinds?of?BacteriaDilution 1∶2?1∶4?1∶8?1∶16?1∶32?1∶64?1∶128?1∶256?Positive?NegativeFactor Control ControlStreptococci?A + + + + + + + + - +Streptococci?B - - - - - - + + - +Staphylococcus?Aureus + + + + + + + + - +Bacillus
Diphtheriae + + + + + + + + - +Typhoid
Bacillus + + + + + + + + - +Bacillus
Dysenteriae + + + + + + + + - +“+”means?Bacteria?is?active；“-”means?no?Bacterial?growth.Table?9?Image?Analysis?of?Schizonepetin’s?Activity?on
Sweat?Gland?Epithelia?of?Rats’Toes(four?fields?of?view,the?total?statistical?area?is?109809.97μm 2)
Dose Physalis Physalis Digital Areal DensityGroup Num (mg/kg) Number Area Density (×10 -4)
(um 2) (×10 -5)Normal?Saline 10 / 12.1?±2.2 572.7±123.0 1.1±0.2 5.22±1.12SchizonepetinⅠ 10 2.0 18.0±1.6 977.2±170.3 1.6±0.1** 8.91±1.55**SchizonepetinⅡ 10 4.0 20.1±2.6 1296.5±175.6 1.8±0.2** 11.81±1.60**SchizonepetinⅢ 10 8.0 19.0±1.8 1193.7±193.5 1.7±0.2** 10.87±1.76**Pilocarpine 10 35.0 19.3±2.6 909.5±146.9 1.8±0.4** 8.28±1.34**SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?doseSchizonepetinⅢ(S3):higher?doseVs?Normal?Saline?group? **P＜0.01(t)
Embodiment 8. Schizonepetolactones are to the influence of hemorheological property
[method] gets 50 of 150-200g rats, and the numbering of weighing is divided into 5 groups at random, every group of male and female half and half.Each organizes 1 hour instantaneous two hind leg (organizing morphologic observation to use for the sweating experiment) that block of neat condyle joint after administration, gets the about 5ml of blood in rat eye socket venous plexus at once, with heparin sodium (0.2ml/ pipe) anti-freezing.The individual layer filtered through gauze is to remove blood clot.Place whizzer to get blood plasma in centrifugal 10 minutes anticoagulation, with its specific viscosity of determination of plasma with 2000rpm.The detection index is as follows:
Whole blood contrast viscosity=whole blood flow velocity (second)/NS flow velocity (second)
The whole blood contrast viscosity of low shear rate, middle shear rate and high shear rate calculates respectively.
Plasma viscosity=plasma flow rate (second)/NS flow velocity (second)
RBC hematocrit (HCT): the whole blood mixing is injected in the RBC hematocrit pipe, with 3000rpm centrifugal 30 minutes, observe RBC hematocrit pipe scale (white corpuscle partly is not counted in).
[result] Schizonepetolactone can make the rat whole blood viscosity reduce, and the RBC aggregate index is reduced, thereby blood viscosity lowering improves hemorheology.As show 10:Table 10 Effect of Schizonepetin on Hemorrheology of Rats
Dose Whole?Blood?Specific?Viscosity RBCGroup Number (mg/kg)
L.T. M.T. H.T. Aggregation
(8?1/S) (60?1/S) (120?1/S) IndexNormal?Saline 10 / 15.25±2.26 7.59±1.19 5.84±0.74 2.90±0.45SchizonepetinⅠ 10 5.0 16.46±2.01 7.27±0.63 5.62±0.25 3.28±0.82SchizonepetinⅡ 10 10.0 13.69±1.48 6.78±0.32 * 4.86±0.30 **?2.66±0.68SchizonepetinⅢ 10 20.0 10.9±2.04 ** 6.18±1.30 * 4.80±0.85 * 3.11±0.80Pilocarpine 10 35.0 11.4±0.91 ** 6.12±0.81 **?4.90±0.57 * 2.50±0.23 *SchizonepetinⅠ(S1):lower?dose；SchizonepetinⅡ(S2):intermediate?doseSchizonepetinⅢ(S3):higher?doseVs?Normal?Saline?group? *P＜0.05? **P＜0.01
The bacteriostatic test of embodiment 9. Schizonepetolactones
[result] Schizonepetolactone soup has stronger anti-microbial effect (its MIC is 0.08mg/ml) to beta streptococcus, and not obvious to other bacterial classification antibacterial effects, sees Table 11.
Table?11?Effect?of?Schizonepetin?on?some?kinds?of?BacteriaDilution 1∶2?1∶4?1∶8?1∶16?1∶32?1∶64?1∶128?1∶256?Positive?NegativeFactor Control ControlStreptococciA + + + + + + + + - +Streptococci?B - - - - - - + + - +Staphylococcus?Aureus + + + + + + + + - +Bacillus
Diphtheriae + + + + + + + + - +Typhoid
Bacillus + + + + + + + + - +?Bacillus
Dysenteriae + + + + + + + + - +“+”means?Bacteria?is?active；“-”means?no?Bacterial?growth.

Claims (9)

1. Schizonepetolactone is characterized in that molecular formula is C 10H 14O 3, fusing point is 188-189 ℃, its specific rotatory power is [α] D 20=+46.70, have following structure:
Figure A0110818600021
2. the extracting method of the described Schizonepetolactone of claim 1 is characterized in that comprising the steps:
A. the schizonepeta medicinal material is extracted with the ethanol heating, gets ethanol extract, get pure medicinal extract behind the ethanol extract decompression recycling ethanol,
B. the pure medicinal extract ethyl acetate extraction that the A step is obtained gets acetic acid ethyl ester extract with acetic acid ethyl acetate extract reclaim under reduced pressure ethyl acetate,
C. acetic acid ethyl ester extract is carried out column chromatography with chromatographic silica gel dress post, carries out gradient elution, collect stream part of containing Schizonepetolactone, leave standstill and separate out coarse-grain, be the Schizonepetolactone crude product with petroleum ether-ethyl acetate,
3. extracting method according to claim 2 is characterized in that Schizonepetolactone crude product ethyl acetate-sherwood oil recrystallization is obtained the granular crystal of Schizonepetolactone, and purity is more than 99%.
4. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare anti-common cold virus medicine.
5. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare anti-inflammation drugs.
6. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare the medicine that suppresses beta streptococcus.
7. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare analgesic agent.
8. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare Claritin.
9. the purposes of the described Schizonepetolactone of claim 1 is characterized in that being used to prepare sudorific.
CNB011081864A 2001-04-09 2001-04-09 Schizonepeta lactone and its extraction process and use Expired - Fee Related CN1174973C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB011081864A CN1174973C (en) 2001-04-09 2001-04-09 Schizonepeta lactone and its extraction process and use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB011081864A CN1174973C (en) 2001-04-09 2001-04-09 Schizonepeta lactone and its extraction process and use

Publications (2)

Publication Number Publication Date
CN1323793A true CN1323793A (en) 2001-11-28
CN1174973C CN1174973C (en) 2004-11-10

Family

ID=4657069

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB011081864A Expired - Fee Related CN1174973C (en) 2001-04-09 2001-04-09 Schizonepeta lactone and its extraction process and use

Country Status (1)

Country Link
CN (1) CN1174973C (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1331861C (en) * 2002-04-03 2007-08-15 纳幕尔杜邦公司 Production of dihydronepetalactone by hydrogenation of nepetalactone
CN101885715A (en) * 2010-07-06 2010-11-17 南京中医药大学 Preparation method for nepetalactone
CN102942545A (en) * 2012-12-07 2013-02-27 南京中医药大学 Nepetalactone-o-bromobenzoic acid ester as well as preparation process and use of nepetalactone-o-bromobenzoic acid ester
CN102942544A (en) * 2012-12-07 2013-02-27 南京中医药大学 Nepetalactone trifluoromethyl benzoate as well as preparation process and use of nepetalactone trifluoromethyl benzoate
CN102964321A (en) * 2012-12-03 2013-03-13 南京中医药大学 Nepetalactone fluorobenzoate, preparation technology and usage thereof
CN103012338A (en) * 2012-12-07 2013-04-03 南京中医药大学 Nepeta lactone parabromobenzoate and preparation process and application thereof
CN105941399A (en) * 2016-05-09 2016-09-21 福建省农业科学院植物保护研究所 Protective agent for ladybug eggs
CN107823199A (en) * 2017-11-13 2018-03-23 青岛大学附属医院 Application of the nepetalactone derivative in nerve degenerative diseases are treated

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1331861C (en) * 2002-04-03 2007-08-15 纳幕尔杜邦公司 Production of dihydronepetalactone by hydrogenation of nepetalactone
CN101885715A (en) * 2010-07-06 2010-11-17 南京中医药大学 Preparation method for nepetalactone
CN101885715B (en) * 2010-07-06 2012-05-23 南京中医药大学 Preparation method for nepetalactone
CN102964321A (en) * 2012-12-03 2013-03-13 南京中医药大学 Nepetalactone fluorobenzoate, preparation technology and usage thereof
CN102964321B (en) * 2012-12-03 2014-11-19 南京中医药大学 Nepetalactone fluorobenzoate, preparation technology and usage thereof
CN102942545A (en) * 2012-12-07 2013-02-27 南京中医药大学 Nepetalactone-o-bromobenzoic acid ester as well as preparation process and use of nepetalactone-o-bromobenzoic acid ester
CN102942544A (en) * 2012-12-07 2013-02-27 南京中医药大学 Nepetalactone trifluoromethyl benzoate as well as preparation process and use of nepetalactone trifluoromethyl benzoate
CN103012338A (en) * 2012-12-07 2013-04-03 南京中医药大学 Nepeta lactone parabromobenzoate and preparation process and application thereof
CN102942544B (en) * 2012-12-07 2014-08-27 南京中医药大学 Nepetalactone trifluoromethyl benzoate as well as preparation process and use of nepetalactone trifluoromethyl benzoate
CN105941399A (en) * 2016-05-09 2016-09-21 福建省农业科学院植物保护研究所 Protective agent for ladybug eggs
CN105941399B (en) * 2016-05-09 2018-06-22 福建省农业科学院植物保护研究所 A kind of protective agent of Ladybird egg
CN107823199A (en) * 2017-11-13 2018-03-23 青岛大学附属医院 Application of the nepetalactone derivative in nerve degenerative diseases are treated

Also Published As

Publication number Publication date
CN1174973C (en) 2004-11-10

Similar Documents

Publication Publication Date Title
CN1891240A (en) Chinese medicine composition containing multi glossy ganoderma active constituents and its preparing method
WO2013010489A1 (en) Eucommia extract, preparation method therefor and use thereof
CN104224811A (en) Salvia miltiorrhiza medicine and preparation method thereof
CN1323793A (en) Schizonepeta lactone and its extraction process and use
CN107827864A (en) Pepper Bi roots of grass compositions dichloromethane extracts regiochemistry method of separating component and purposes
WO2017092230A1 (en) Biflavone compound and uses thereof for treating cancers and preparing drugs
CN107987089B (en) A kind of extract, preparation method and medical usage rich in chromene lactone
CN1915986A (en) High purified tanshinone IIA sodium sulfonate, fabricating method, and preparation
CN1259068C (en) Dogwood extraction and its preparation method and usage
US11571453B2 (en) Piper laetispicum extract and preparation method therefor and use thereof
CN1626545A (en) Compound extracted from hull and stem of yellow horn, extracting method and application
CN1762359A (en) Lindera root alkaloid, its preparation method and application in medicine preparation
CN1506090A (en) Rheum emodi wall extract and medicine composition with the extract as active component
CN103626812A (en) Novel parishin compound in gastrodia elata and application of compound
CN1686141A (en) Medicinal composition for treating hepatitis and diabetes
CN108478540B (en) Preparation method of tripterygium wilfordii slow-release microcapsule
CN105753830A (en) Estazolam medicine composition and application thereof in biological medicine
CN104130232B (en) The method of purification of a kind of EGCG and the EGCG of acquisition and pharmaceutical composition
CN1511573A (en) Medicinal composition for preventing and curing prostatitis and hyperplasia of prostate and its preparing method
CN110283151A (en) A kind of preparation and its application of Chinese medicine Centipeda minima sesterterpenoids monomer
CN105193835B (en) Liriodendrin and its aglycon are preparing the purposes in preventing pyemia Lung Injury drug
CN1176677C (en) Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process
CN103113196A (en) Glechoma longituba phenol, and preparation method and application thereof
CN1628649A (en) Pharmaceutical combination containing red sage root element and preparation method thereof
CN1772753A (en) Chinese medicine active compound component for treating senile dementia and its prepn and use

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Nanjing University of Chinese Medicine

Document name: Qualified notice of first instance

C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Nanjing University of Chinese Medicine

Document name: Notification of registration; notice of patent for invention

C14 Grant of patent or utility model
GR01 Patent grant
C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Huang Jiadong

Document name: Deemed a waiver of patent notice

Addressee: Huang Jiadong

Document name: Deemed a waiver of a patent claim

CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20041110

Termination date: 20160409

CF01 Termination of patent right due to non-payment of annual fee