CN1237972C - Active component of muskrat fragrant, preparing technique and usage - Google Patents
Active component of muskrat fragrant, preparing technique and usage Download PDFInfo
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Abstract
The present invention discloses an active component of American musk, and a preparation process thereof, which is characterized in that the active component comprise the fatty acid of C1 to C28 and ester thereof, macrocyclic ketone and steroid. The preparation process comprises the following steps: the natural musk is saponified in a basic alcoholic solution; after the saponified liquid is acidified by strong acid, the saponified liquid is extracted and separated by diethyl-ether, and then a methyl ester reaction is carried out; next, an oxidant is added, and oxidizaton and degradation reactions are carried out to obtain the active component of American musk. The preparation process has the advantages of simple and easy operation, stable product quality and high yield, and is suitable for large-scaled industrial production. The active component of American musk can replace musk to be used as a new natural medicine or medicinal material and spice thereof. In addition, the active component of American musk has the advantages of small toxicity, no stimulation and easy storage.
Description
Technical field
The present invention relates to a kind of muskrat musk active component, preparation technology and uses thereof, or rather, is to extract the muskrat musk active component from the sachet secretions of muskrat.
Background technology
Both at home and abroad, Moschus is regarded as precious natural perfume material, and as senior essence fixastive, it is diffusing that fragrance is waved slowly.Moschus or rare Chinese medicine have " lead to all keys, open meridians " simultaneously, invigorate blood circulation, and eliminating stagnation, the analgesic effect is used for calentura, infantile convulsion, apoplexy, coma, trusted subordinate's sudden pain, angina pectoris, injury from falling down, diseases such as ulcer sores.There is important role Moschus side in medicine, the many famous Chinese patent medicines of China all have the Moschus compatibility as rejuvenate ball, LIUSHEN WAN, Pien Tze Huang, HONGLING SAN, Moschus Calculus Bovis side, Moschus Realgar ball, Borneolum Syntheticum Resina garciniae side etc. of Chinese medicine children's.Medicinal Moschus is mainly derived from the Moschus moschiferous deer, and the wild resource of Moschus moschiferous deer is day by day rare, experimental stage in artificial domestication is among a small circle, in recent years, the natural Moschus waits the animal perfume material inadequate resource, and supply falls short of demand, all seeking new resource both at home and abroad, the new resources of therefore seeking Moschus are problems anxious to be solved.
Muskrat (Ondatra Zibethica) is the fur-bearing animal of the phytophage preciousness of Rodentia Cricetidae, and adaptability is strong, and breeding is fast, easily raises good management, and artificial breeding's cost is also cheap, is a kind of precious economic animal.Male muskrat have a pair of scent gland under abdomen by between skin and the muscle, its secretions muskrat musk gives off a strong fragrance.Muskrat musk is that the public muskrat of rodent mating period is by excretory milky material in the muskrat musk glandular sac; Character: milky grease is soluble in organic solvent, the water fast; Abnormal smells from the patient: soft delicate fragrance, strong, lasting, lasting.Contain macrocycle molecule chemical compounds such as cyclopentadecanone in the discovery muskrat scent glands such as Stevens in 1945, find that also the muskrat scent gland has the abnormal smells from the patient of similar Moschus, thereby caused relevant scholar's extensive concern both at home and abroad.
People (1973) such as U.S. Van Dorp are referred to as american musk (America musk), and therefrom detect macrocyclic ketone, ester and fatty acid composition.The antiinflammatory of muskrat musk, anoxia enduring, decreased heart rate, bring high blood pressure down and to reduce negative inotropic action such as myocardial oxygen consumption etc. similar to the natural Moschus, also have various active such as the growth of animal of promotion.Prove by chemical analysis, contain muscone (muscone in the muskrat musk, 3-methyleyelopen tadenone), also contains compositions such as normuscone, 17 cyclanones, ester and multiple fatty acid, on spice and a day chemical industry, medical industry, have important economic value.For this reason, carry out the research of muskrat musk spice new product, animal perfume material extremely in the exhaustion in the world, exploitation animal perfume material new product will play a significant role to the development of world's animal perfume material industry.
Wait under the situation of animal perfume material inadequate resource present natural Moschus, replace Moschus moschiferous to get perfume (or spice) by muskrat, it is a developing direction, scholar both domestic and external is being devoted to this research, and the report of correlational study is all arranged as Gao Yun, Heilongjiang Province university of TCM, Heilongjiang Prov. Wild Animal Inst. etc.But the exploitation about muskrat musk still is in theoretical research and analysis phase at present, does not enter the suitability for industrialized production stage, make muskrat real " getting perfume (or spice) for Moschus moschiferous ", must industrial realization muskrat musk extraction of active ingredients.
The fragrance that the excretory former perfume (or spice) of muskrat is had can not be directly as fragrance applications, the saturated bond of compositions such as macro ring ketone, fatty acid and esters must be opened, form unsaturated bonds such as ethylene linkage or acetylene bond, could fully show the true colours of muskrat musk as natural animal spice, the spice that embodies its muskrat musk is worth and the effect of the refreshment medicine of having one's ideas straightened out, and contains a large amount of satisfied fatty acid in the natural muskrat musk and also influence its drug effect; Simultaneously natural muskrat musk also exists and is difficult for preserving, and freshness date is short, and the long-time storage rotten deactivated deficiency of easily becoming sour is so will improve the drug effect and the application thereof of muskrat musk, process technology that just must the natural muskrat musk of research.
Summary of the invention
The object of the present invention is to provide a kind of muskrat musk active component, described muskrat musk active component contains a large amount of unsaturated fatty acids and esters thereof, has good biological activity, the active component that can replace the natural Moschus, and be easy to store, toxicity is little, has no stimulation.
Another purpose of the present invention is to provide a kind of preparation technology of muskrat musk active component, and described preparation is simple, constant product quality, and the productive rate height is fit to large-scale industrial production.
Still a further object of the present invention is to provide a kind of purposes of muskrat musk active component.
The invention provides a kind of muskrat musk active component, it is characterized in that comprising fatty acid and esters, macrocyclic ketone and the steroidal class composition of carbon to two 18 carbon.
The content of muskrat musk active component of the present invention is:
C
1～C
28Fatty acid and esters 50%～80% thereof
Macrocyclic ketone 18%～45%
Steroidal class 1%～5%.
Muskrat musk active component of the present invention also contains aminoacid, and total nitrogen content is 0.5%～1%; Described aminoacid comprises 16 kinds, is aspartic acid, threonine, serine, glutamic acid, proline, liver propylhomoserin, alanine, methionine, isoleucine, leucine, lysine etc.
Fatty acid and the esters thereof that contains carbon to two 18 carbon of the present invention can be unsaturated fatty acid and esters and satisfied fatty acid and esters thereof, its content ratio is 5: 3, described unsaturated fatty acid and esters thereof can be: contain the olefin(e) acid of carbon to two 18 carbon or the esters of olefin(e) acid, as: tetradecenoic acid, eicosenoic acid, 14 alkynes-[13]-olefin(e) acid, 8, the 11-eicosadienoic acid, two dodecadienoic acids, hexadecenoic acid, tricosadienoic acid, tetracosandienoic acid, the eicosadienoic acid ethyl ester, hexacosandienoic acid, the eicosylene acetoacetic ester, hexacosenoic acid, cerotene acid, the docosenoic acid ethyl ester, two octadecadienoic acids, the tetracosandienoic acid ethyl ester, the tetracosene acetoacetic ester, the ppentacosene acetoacetic ester, the hexacosandienoic acid ethyl ester, the cerotene acetoacetic ester, kinds more than 20 such as two octadecadienoic ethyl ester; Described satisfied fatty acid and esters thereof can be: nine carbonic acid, lauric acid, 18 carbonic acid, ten tetra-carbonics, the octadecenoic acid isomer, 16 carbonic acid, two ficocerylic acids, (2)-9-18 ethyl carbonates, 18 ethyl carbonate allosomes, 25 carbonic acid, methyl-19 methyl carbonate, 26 carbonic acid, 20 ethyl carbonates, ethyl myristate, 15 ethyl carbonates, 2-methyl-16 methyl carbonate, 10-methyl-17 methyl carbonate, methyl-26 methyl carbonate, kinds more than 20 such as 16-methyl-17 methyl carbonate; Described macrocyclic ketone is 15 cyclanones, ten five rings ketenes, 17 annulenones and 17 cyclanones etc.; Described steroidal class is the shining diene of gallbladder steroid and gallbladder steroid-5-alkene-3-alcohol etc.
The raw material that the present invention selects for use is natural muskrat musk, selects the scent gland of bull muskrat, adopts the artificial live body of non-narcotic method to get fragrant method collection.
Natural muskrat musk is got the usefulness gas phase color-mass spectral analysis of fragrant back through aseptic, its macrocyclic ketone, and organic acid esters, its result is as follows: contain macro ring ketone and organic acid ester, the macro ring ketone is 15 cyclanones and 17 cyclanones; Organic acid ester is 2-methyl 16 methyl carbonates, second-9-18 carbonic acid olefin(e) acid ethyl esters, 16 ethyl carbonates, methyl palmitate, methyl myristate, gaidic acid methyl ester, octadecenic acid methyl ester, Methyl Stearate and 18 dienoic acid methyl ester.
For biological activity and the storage life thereof that increases muskrat musk, natural muskrat musk must be carried out chemical treatment.
The preparation technology that muskrat musk active component of the present invention adopts is: the alkaline alcohol solution saponification of natural muskrat musk, saponification liquor are after the strong acid acidify, and extracted with diethyl ether is separated, and again through esterification reaction of organic acid, oxidizer obtains the muskrat musk active component through oxidative degradation.
Specifically, the invention provides a kind of preparation technology of muskrat musk active component, this technology may further comprise the steps:
1. it is an amount of) to get natural muskrat musk, carries out saponification with alkaline alcohol solution, concentrates the back thin up, after the strong acid acidify, and with solvent extraction extraction, combining extraction liquid, dry total fatty acids;
2.) with the gained total fatty acids, behind esterification reaction of organic acid,, be washed to neutrality with the solvent extraction extraction, drying gets the esterification material;
3.) concentrated solution is dissolved in acetone or the acetone-benzene, oxidizer is carried out oxidative degradation then, adds the acidic materials acidify after leaving standstill, and is washed to neutrality, and extracts with solvent extraction, the dry muskrat musk active component that gets.
Step 1) wherein of the present invention also can be: natural muskrat musk can be used organic solvent extraction earlier before with the alkaline alcohol solution saponification; Described organic solvent is petroleum ether, acetone, chloroform, benzene, ether, alcohol-ether or ethyl acetate etc., and addition is 5～10 times of muskrat musk.The purpose that adopts this step is in order better to extract required fatty acid.
The temperature of the saponification described in the step 1) is 60 ℃～90 ℃, described alkaline alcohol solution is for containing alkaline 60%～95% methanol of 0.5M～2M or alcoholic solution, described highly basic can be KOH or NaOH, addition is 1～4 times of natural muskrat musk, and the described saponification time is 3～12 hours; Described concentrated back thin up adds 2～5 times water of concentrated solution again for to be concentrated into 1/3～3/4 of original solution earlier; Described strong acid is H
2SO
4Or HCl, concentration is 1M～5M, adjusting pH value is 1～4; The extraction solvent for use is ether, acetone or dichloromethane benzene etc., and extraction times is 3～10 times, and each addition is 10～20 times of natural muskrat musk; Mixing speed during extraction is 20～100 commentaries on classics/per minutes, and the amount of the total fat of dry back gained is the 40%-80% of natural muskrat musk;
Step 2) the esterification reaction of organic acid temperature described in is 15 ℃～40 ℃, can adopt the methanol-ether solution esterification of Azimethylene .ization, used concentration is 1～5: 9～15, addition is 1.5～5 times of total fatty acids amount, the return time of esterification reaction of organic acid is 1～5 hour, also can adopt concentration is that 90%～100% addition is 5～10 times the absolute methanol or the three boron methane of total fatty acids amount, after most solutions is removed in steaming, be concentrated into 1/4～3/4 of original solution, add 2～5 times water dilution of concentrated solution again; The extraction solvent for use is ether, acetone, dichloromethane or benzene etc., addition is 8～20 times of solution amount, be extracted to liquid colourless till, combining extraction liquid, be washed to neutrality, with 3～5 times of anhydrous sodium sulfate dryings of solution amount, dry back gained esterification amount of substance is the 30%-60% of natural muskrat musk.
The addition of the acetone described in the step 3) or acetone-benzene is 2～5 times of esterification amount, and the concentration ratio of described acetone-benzene is 1: 1, and described oxidant is KMnO
4, addition is 1～2 times KMnO
4, the solution purple is not disappeared till; Left standstill 0.5～2 hour under 15 ℃～25 ℃ conditions, described acidic materials are H
2SO
4Or HCL, control PH1～3, H
2SO
4Addition be 1～10 times of solution amount, concentration is 0.5～5M; Be washed to neutrality, the extraction solvent for use is ether, acetone, dichloromethane or benzene etc., and extraction times is 3～10 times, and each addition is 10～20 times of solution amount; The amount of dry back gained muskrat musk active component is 30%-55%.
Also can carry out drying earlier after adding the acidic materials acidify in the step 3), described desiccant is solid sodium sulfite, calcium carbonate, sodium sulfate or copper sulfate etc., and addition is 3～10 times of solution amount.
The present invention adopts the method for extracting muskrat musk volatile oil active component can be: get natural muskrat musk and adopt the vapor distillation method distillation after 1～5 hour, ether, acetone, dichloromethane equal solvent extraction with 8～15 times of former states extract 1～5 time, remove solvent, drying, getting white oily mater is the volatile active component of muskrat musk.The yield of the volatile active component of gained muskrat musk is 80～90%.
The dry desiccant such as anhydrous sodium sulfate, sodium sulfite, sodium sulfate, sodium sulfite or copper sulfate that adopt of the present invention, addition is 3～5 times of dry thing amount; Reclaim solvent and can adopt the evaporation of low temperature rotary evaporator, adopt the method can reduce the loss of low boiling component; Mixing speed when the present invention extracts is 20～100 commentaries on classics/per minutes.
Muskrat musk volatile oil component of the present invention is: decine, enanthaldehyde, 7-(1-methyl ethylidene)-norbornane, 1-methyl-4-(1-Methylethyl)-cyclohexane extraction, octanal, methyl (1-Methylethyl) benzene, aldehyde C-9, capraldehyde, 4-methyl-2-propyl group-1-becomes alcohol, 2-11 (alkane) olefine aldehydr, 2 hydrogen-5-amyl group-2 (3H)-furanone, enanthic acid, sad, n-nonanoic acid, cyclopentadecanone and cyclopentadecylene ketone, 17 cyclanones and 17 cycloalkanes ketenes, 10-hendecoic acid monooctyl ester, the hiragonic acid methyl ester, 1,7,7 trimethyls-three ring, the 6-heptane, 1-methyl-4-(1-Methylethyl)-cyclohexane, 4-methyl isophthalic acid-(1-Methylethyl-cyclic ethylene), the 2-decanone, 1-decanol, the hendecanal, the 2-undecenal, 6, the 10-dimethyl-(E)-5,9-11 carbon diene-2-ketone, 1, the 12-dodecanediol, 9-vaccenic acid aldehyde, 2,6,10,15-tetramethyl heptadecane, pentatriacontane.
The muskrat musk active component that preparation technology of the present invention obtains adopts laboratory facilities analyses such as thin layer chromatography, ultraviolet spectra, infrared spectrum, gas chromatogram, gas chromatography/mass spectrometry instrument, and the muskrat musk active component contains fatty acid and esters, macrocyclic ketone and steroidal become to grade.
The present invention also provides the purposes of muskrat musk active component in pharmacy, food, daily-use chemical industry.
The application of muskrat musk active component of the present invention in the medicine of preparation treatment myocardial ischemia, ischemia, anticoagulant, inhibition thrombosis, coronary heart disease, vasculitis etc.
The application of muskrat musk active component of the present invention in the medicine of preparation treatment or prevention of inflammation disease.
Muskrat musk active component of the present invention is in preparation treatment or prevent application in the medicine of anti-pentobarbital sodium sleep, growth promoter etc.
Muskrat musk active component of the present invention is as the purposes of lasting agent, fixastive.
Muskrat musk active component of the present invention can be made dosage forms such as this area tablet commonly used, capsule, drop pill, taking convenience as medicine or food.
The present invention finds the result of study of the pharmacologically active of described muskrat musk active component:
1. the influence to anesthetized dog hemodynamics and myocardial oxygen consumption shows: the muskrat musk active component can reduce arteriotony, and total peripheral resistance is descended; Reduce myocardial oxygen consumption; Can prolong clotting time; The energy anticoagulant; Can suppress the formation of thrombosis;
2. the influence to the rat experiment foot swelling shows: the muskrat musk active component has anti-inflammatory effect;
3. the anoxybiotic influence of white mice is shown that the muskrat musk active component has oxygen lack resistant function;
4. the influence to pentobarbital sodium sleep effect shows the effect that the muskrat musk active component can significantly curtail sleep;
5. the muskrat musk active component has a bacteriostasis to external;
6. the muskrat musk active component has somatotrophic effect to animal;
7. safety experiment shows non-stimulated symptom of muskrat musk active component and anaphylaxis.
Can draw from above research and the invention has the advantages that:
1, the present invention replaces natural Moschus's effective active to known natural muskrat musk, thereby determines the medical usage of muskrat musk, has opened up a new application.
2, muskrat musk safety non-toxic of the present invention, pharmacological action is better than natural muskrat musk, is indicating well prospect in medicine.
3, raw material sources of the present invention are abundant, can open up out the agricultural product industrialized development, and medicinal part is cheap, does not see toxic and side effects, and preparation technology is simple, and good to eat system of mourning becomes dosage forms such as tablet, capsule, drop pill, and is easy to use.
4, folk prescription of the present invention is mixed with medicine and has remarkable reduction vascular resistance, reduces arteriotony, reduces the heart burden, reduces the myocardial oxygen consumption effect, helps treating coronary heart disease.
5, folk prescription of the present invention is mixed with medicine the effect of the platelet aggregation of inhibition collection, prolongs clotting time, helps the sequela of preventing and treating cerebral thrombosis and causing.
6, the present invention has the effect that significantly curtails sleep to pentobarbital sodium sleep effect, also has the effect of significant antiinflammatory action and promotion growth promoter simultaneously.
7, show through clinical trial, natural muskrat musk of the present invention through be processed into muskrat musk its oral after instant effect, evident in efficacy, and do not have toxicity.
8, muskrat musk is better than the reason of natural muskrat musk: the active component of natural muskrat musk is except that muscone on the one hand, also have a large amount of satisfied fatty acid, protein etc., and the active component of muskrat musk contains on the muscone basis at natural muskrat musk and satisfied fatty acid is become unsaturated fatty acid, removed adiaphorous protein, increase its defying age, removed free radical, reduce myocardial oxygen consumption, prolong the platelet aggregation collection time, suppress thrombosis, strengthened antiinflammatory action, shorten the length of one's sleep of pentobarbital sodium, promoted therapeutical effect such as growth promoter.On the other hand, natural muskrat musk is to take out from the sachet of animal, and freshness date is short, and long-time storage is easily become sour to go bad and lost activity, and muskrat musk is the active component that obtains through after the processing, and is neither apt to deteriorate, also preserves easily.A bit be noted that in addition and utilize natural muskrat musk volatile component, must make the effect that really to play the refreshment of having one's ideas straightened out and the fragrance effect that guarantees cosmetics of everyday use by method of the present invention as refreshment medicine and the agent of change lasting of having one's ideas straightened out.
It is of the present invention that preparation is simple, constant product quality, and the productive rate height is fit to large-scale industrial production.Adopt the muskrat musk active component of preparation method gained of the present invention owing to contain a large amount of unsaturated fatty acids, increased biological activity, be suitable for as natural drug medical material and spice thereof, show that through a large amount of experiments the muskrat musk active component not only has antiinflammatory, the sleep of anti-pentobarbital sodium and pharmacological action such as antibacterial, and aspect cardiovascular, also have great pharmacological effects, a negative inotropic action; Reduce the myocardial oxygen consumption effect significantly, be secondary to after the hemodynamics depression effect, the resistance of blood vessel reduces, the burden of heart alleviates, and reduces the utilization of blood oxygen, this biological activity may over-burden to heart, especially comparatively favourable to preventing and treating cardiac hypertrophy and coronary heart disease.Simultaneously in filed of daily-use chemical industry, especially the muskrat musk active component can be used as lasting agent, fixastive in cosmetics industry, and the toxicity of muskrat musk active component is little, having no stimulation and being easy to stores, and muskrat musk active component of the present invention can replace Moschus moschiferous to become new natural drug medical material and spice thereof.
The specific embodiment
Below be embodiments of the invention, the embodiment that the present invention provides is in order to further specify the specific embodiments of the invention scheme, rather than is used for limiting protection scope of the present invention.
Embodiment 1
Present embodiment relates to the pharmacologically active experiment of muskrat musk active component of the present invention.
One. the safety experiment of muskrat musk active component
1. the acute toxicity test of white mice
A, oral administration: get 10 of white mice, female, hero half and half, body weight 20 ± 2.0g, the normal saline solution of making 50% muskrat musk pours in the stomach by the 820mg/kg muskrat musk, observes none only death after three days.
B, drug administration by injection are got 10 of white mice, female, hero half and half, and body weight 20 ± 2.0g with the normal saline solution lumbar injection 1000mg/kg administration of 10% muskrat musk, calculates by simplifying probit method, records:
LD
50(Ip)＝15.14+6.52g/kg LD
50(iV)＝13.14+3.58g/kg
2. the hypersensitive test of white mice
Give a tail vein injection muskrat musk of white mice 770mg/kg, observed 72 hours, do not have death, the outward appearance behavior does not also have significant change, shows that Moschus toxicity is lower, LD
50More than 770mg/kg.Other gets Cavia porcellus and shaves the light ventral seta, embrocates 4% muskrat musk normal saline emulsion, and continuous 6 days, muskrat musk was to local non-stimulated symptom of Cavia porcellus and anaphylaxis, and preliminary experiment shows that muskrat musk uses also safer in cosmetics industry.
Two. muskrat musk and natural Moschus are to the influence of anesthetized dog hemodynamics and myocardial oxygen consumption
The animal dog, body weight 13.8 ± 0.7kg purchases Xiyuan hospital in Beijing academy of traditional Chinese medicine.White mice, body weight is 20g, purchases in Norman Bethune Medical University, Changchun laboratory animal room.
Method and result:
9 of dogs, male and female dual-purpose, the sodium intravenous anesthesia of pentobarbital.Chen Zhi and operative procedure are adopted in this experiment, and application MPU-0.5 pressure transducer is averaged arteriotony (MAP), MF-27 type square wave cmf record cardiac output (CO), coronary flow (CBF) and handle left ventricular pressure (LVP) and the left ventricular pressure maximum climbing speed (LV dp/dt max) that obtains through pressure transducer and differentiator is with the electrocardiogram dipstick metering rate (HR) of coring.Separate external jugular vein and femoral artery simultaneously, divide shape venous oxygen amount (CVO) and femoral artery blood oxygen amount (AO) with the plastic bushing that is filled with heparin-saline, more than seven indexs (except that HR) synchronous recording lead on the physiograph in eight.Calculate total peripheral resistance (TPR), myocardial oxygen consumption (MHO) and three secondary parameters of blood coefficient of oxygen utilization (OUR) again.
After treating that above-mentioned every hemodynamics and the every index of blood oxygen are stable, iv muskrat musk and natural Moschus 24mg/kg respectively, injection finishes in 30 seconds, 1,5,10,15 and 30 minute These parameters before the record administration and behind the iv, blood oxygen index only is measured to 15 minutes.
1, muskrat musk and natural Moschus are to the influence of anesthetized dog arteriotony, left indoor pressure, the maximum climbing speed of left indoor pressure and total peripheral resistance.
Experiment shows muskrat musk and natural muskrat musk decreased heart rate and reduces arteriotony more obvious than the natural Moschus, and muskrat musk is more obvious than natural muskrat musk.
2, muskrat musk and natural Moschus are to the influence of anesthetized dog cardiac muscle blood oxygen metabolism
The iv muskrat musk is different to the effect of anesthetized dog CVO, AO, MHO and OUR with natural Moschus 24mg/kg, and muskrat musk significantly increases CVO, reduces AO, and it is obvious with minimizing OUR to reduce MHO, and the natural Moschus does not have this effect.
Table 1 muskrat musk and natural Moschus are to the influence of anesthetized dog CVO, AO, MHO and OUR
| Muskrat musk (n=4) | ||
| Before the administration | After the administration (min) | |
| 1 5 10 15 | ||
| CVO(ml/100gcm/min) | 4.13±0.82 | 0.33±0.13 1.20±0.23 *Δ 1.28±0.33 *ΔΔ 10.10±0.17 ** |
| AO(ml/100gcm/min) | 10.85±0.38 | -0.58±0.16 *Δ -1.75±0.27Δ 1.60±0.86 -1.68±0.82▲ |
| MHO(ml/100gcm/min) | 2.01±2.76 | 0.38±0.10 *ΔΔ -0.90±0.33▲ -0.94±0.40Δ -0.90±0.82▲ |
| OUR(％) | 62.10±2.76 | -5.46±1.87Δ -18.35±1.97 **Δ▲ -17.33±1.97ΔΔ ** -17.04±4.57 *▲ |
| Natural Moschus (n=3) | ||
| Before the administration | After the administration (min) | |
| 1 5 10 15 | ||
| CVO(ml/100gcm/min) | 4.60±0.99 | 0.27±0.03* 0.10±0.10 0.13±0.07 -0.77±1.0 |
| AO(ml/100gcm/min) | 10.70±1.02 | 0.90±0.46 1.10±0.17* 0.73±0.03*** 0.90±0.21* |
| MHO(ml/100gcm/min) | 2.68±0.20 | 0.45±0.14 0.65±0.15 0.43±0.22 1.06±0.49 |
| OUR(％) | 56.10±9.52 | 0.74±0.45 2.93±1.34 4.00±0.85* 11.94±11.29 |
3, muskrat musk and natural Moschus to anesthetized dog cardiac output and coronary flow influence iv muskrat musk natural Moschus 24mg/kg, cardiac output and coronary flow are not all had tangible influence.1,5,15 and 30 minute cardiac output natural Moschus is 0.09 ± 0.21 ,-0.02 ± 0.04,0.08 ± 0.03,0.24 ± 0.08 after the administration, and muskrat musk is-0.02 ± 0.031 ,-0.004 ± 0.027,0.047 ± 0.029 and 0.020 ± 0.024.The two is 3.61 ± 2.73,3.33 ± 1.33,3.67 ± 4.18,7.00 ± 15.55 to the coronary flow natural Moschus, and muskrat musk is-1.17 ± 1.25 ,-0.38 ± 0.38,1.67 ± 1.53 and ± 0.33 ± 0.80.The two has difference more significantly to cardiac output (30 minutes) and coronary flow (15 minutes).
4, muskrat musk and natural Moschus are to the influence of animal clotting time
(1) glass capillary method
Get 40 of mices, be divided into 4 groups (table 1) at random, the high and low dose muskrat musk, natural muskrat musk suspension oral gavage, positive controls is irritated stomach with muscone, every day 2 times, continuous 2 days.Administration is for the last time inserted mice endocanthion ball rear vein beard with capillary glass tube after half an hour, about deeply 4-5mm, and autoblood flows in the pipe and picks up counting.Blood is filled with back taking-up capillary tube and is lain against on the table, gets over 0.5cm every 30 seconds capillary tubies that fracture, and slowly draws back to the left and right, and whether observe the place of fractureing has the blood clotting silk, and till occurring to the blood clotting silk, required time is clotting time.
Table 2 muskrat musk and natural Moschus are to the influence (capillary glass-tube method) of clotting time of mice
| Group | Dosage mg/kg | Number of animals/only | Average clotting time ± standard error/minute |
| High dose group | 600 | 10 | 2.81±1.66 |
| Low dose group | 400 | 10 | 5.42±3.12 |
| Positive controls | 10 | 10 | 1.81±1.58 |
| Blank group | Deng capacity | 10 | 1.53±0.29 |
P＜0.05
The result shows that muskrat musk high and low dose group compares with blank group, and group difference is all remarkable, but positive control and the no significant difference of blank group illustrate that muskrat musk can obviously prolong the clotting time of mice, and muscone do not have obvious influence to clotting time of mice.
(2) slide method
Get 40 of mices, grouping and medication are the same.After last administration half an hour, win a branch hole ball rapidly with the curved tweezer of ophthalmology, and at the two ends of microscope slide each liquid of bleeding, the about 5mm of drop of blood diameter, use manual time-keeping immediately, stirred once gently inwards from the drop of blood edge with the cleaning pin every 30 seconds, and observation has or not the blood streak to provoke.End required time and be clotting time to provoking the blood streak from blood sampling beginning.Another is bled and rechecks for last.
Table 3 muskrat musk and natural Moschus are to the influence (slide method) of clotting time of mice
| Group | Dosage mg/kg | Number of animals/only | Average clotting time ± standard error/minute |
| High dose group | 600 | 10 | 2.64±1.59 |
| Low dose group | 400 | 10 | 5.33±3.47 |
| Positive controls | 10 | 10 | 1.71±1.53 |
| Blank group | Deng capacity | 10 | 1.35±0.25 |
Result and preceding a kind of method are identical, illustrate that muskrat musk but can prolong the clotting time of mice, and concentration is the muscone of 10mg/kg the clotting time of mice are not had obvious influence.
5, muskrat musk and natural Moschus are to suppressing hematoblastic gathering
Get 40 of mices, grouping and medication are with 4, and administration is for the last time plucked eyeball after half an hour and got blood, and is centrifugal after anticoagulant, isolates platelet-rich plasma (PRP).
(platelet count is 200,000/mm) to the PRP of absorption 0.1ml, place on common year sheet glass of silicidation, in blood plasma, put into one of iron core glass pellet, to carry sheet glass again is placed on the magnetic stirring apparatus, glass is rotated with the speed of 1000r/min, take off after 5 minutes with the naked eye and the hematoblastic aggregation extent of microscopic examination.
Table 4 muskrat musk and natural Moschus are to the influence (microscopy method) of mouse platelets aggregation capability
| The platelet aggregation classification | Amount to | ||||||
| Group | Dosage mg/kg | Zero level | One-level | Secondary | Three grades | Number of animals/only | Average rank preface value |
| High metering group | 600 | 6 | 1 | 2 | 1 | 10 | 10* |
| Low metering group | 400 | 4 | 2 | 3 | 1 | 10 | 17.56 * |
| Positive controls | 10 | 5 | 2 | 1 | 2 | 10 | 16.80 * |
| Blank group | Deng capacity | 1 | 1 | 2 | 6 | 10 | 17.78 |
*P＜0.05
[notes] zero level: do not have or accidental aggregation＜3; One-level: more, 3～10 platelet of each aggregation, secondary: quite a lot of,＞10 platelet; Three grades of full visuals field
Centrifugal after anticoagulant, isolate the interior result of platelet-rich plasma and show that muskrat musk can suppress hematoblastic gathering.
6, muskrat musk and natural Moschus are to suppressing the influence of thrombosis
Get 40 of male white rats, divide 4 groups, irritate stomach twice every day, connect and to irritate three days, after last administration half an hour, every Mus lumbar injection 10% urethane solution (0.5/kg) anesthesia.After the anesthesia, separate left external jugular vein and right common carotid artery the surgical thread of a long 5cm is put in the stage casing of a polyethylene tube, (50 μ g/ml) is full of the polyethylene tube chamber with heparin-saline solution.One end of pipe is inserted left external jugular vein, be injected into heparin 50 μ g/ml from polyethylene tube.Clamp tube wall, with the other end insertion right common carotid artery of pipe, open blood flow is middle Herba Clinopodii after 15 minutes, takes out silk thread rapidly and weighs again, and gross weight deducts silk thread deadweight weight and is wet weight of thrombus, gets the thrombosis dry weight under the room temperature after dry 24 hours.
Table 5 muskrat musk and natural Moschus coagulate thrombotic influence to rat
| Group | Dosage mg/kg | Number of animals/only | Wet weight of thrombus | The thrombosis dry weight |
| High dose group | 400 | 10 | 14.50±2.64 | 4.57±0.52 |
| Low dose group | 200 | 10 | 38.43±3.85 | 7.30±1.25 |
| Positive controls | 10 | 10 | 19.51±6.61 | 6.60±2.14 |
| Blank group | Deng capacity | 10 | 48.80±19.93 | 8.71±2.06 |
The result shows that muskrat musk suppresses thrombosis, and the formation of rat suppository is all had the obvious suppression effect.
Above-mentioned description of test muskrat musk has the heart rate of slowing down, and reduces arteriotony, increases body's hypoxia tolerance, and anticoagulant prolongs clotting time, suppresses effects such as thrombosis.Therefore muskrat musk also has been described than natural Moschus good effect, this this effect all helps prevention and treatment thrombosis, cerebrovascular accident and sequela that causes and coronary heart disease.
Three. muskrat musk and natural Moschus are to the influence of rat experiment foot swelling
The experiment material of selecting: experiment is purchased the laboratory animal room in the Norman Bethune Medical University with rat and white mice, and Cavia porcellus is purchased in China Academy of Traditional Chinese Medicine, Beijing.The musk tibetene that the natural Moschus provides for Tianjin medical material company (Moschus), is made into 2% concentration with normal saline.Carrageenin is that institute of Chinese materia medica, Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science pharmacological room gives.Dextran is that the Beijing Chemical Plant produces.
Method and result:
1, the influence of on Carrageenan foot swelling
30 of rats, be divided into 5 groups at random, (6 every group) are abdomen injection (ip) hydrocortisone (He) 12mg/kg respectively, irritate stomach (po) and ip muskrat musk 120mg/kg, po Moschus 500mg/kg and normal saline, for three days on end, after the last administration 2 hours, injection 1% carrageenin 0.1ml/ was only down in the right vola aponeurosis (aponeuroses) of rat, measured foot swelling once every 1 hour, survey altogether 6 times.
Table 6 muskrat musk, natural muskrat musk and natural Moschus are to the influence of rat carrageenan foot swelling (X ± SE)
| Group (mg/kg) | Route of administration | Cause scorching back paw swelling (mm) | ||
| 1 | 2 | 3 | ||
| Contrast | ip | 5.33±0.56 | 4.25±0.11 | 4.38±0.31 |
| Hc(12) | ip | 3.33±0.84 | 2.33±0.49 | 3.33±0.79 |
| Muskrat musk (120) | ip | 3.33±0.83 | 2.50±0.42 | 2.58±0.51 |
| Muskrat musk (120) | po | 4.66±0.44 | 3.50±0.41 | 3.92±0.33 |
| Natural muskrat musk | ip | 4.21±0.41 | 3.12±0.39 | 3.72±0.29 |
| Moschus (500) | po | 4.58±0.20 | 3.8.3±0.19 | 3.75±0.23 |
By table as seen, at po and ip muskrat musk, anti-inflammatory effect all occurs in 1-5 hour after causing inflammation, the antiphlogistic effects of ip muskrat musk is more obvious than po.
2, to the influence of dextran foot swelling
24 of rats, 4 groups of branches as shown in table 7 are whenever given ip normal saline, Hc12mg/kg, muskrat musk 120mg/kg and Moschus 120mg/kg respectively, continuous three days, after the last administration 2 hours, in the right vola aponeurosis (aponeuroses) of rat injection 6% dextran 0.1ml/ only (other program is with above-mentioned method) down.
Table 7 muskrat musk, natural muskrat musk and natural Moschus are to the influence of rat dextran arthroncus (X ± SE)
| Group (mg/kg) | Number of animals | Cause scorching back paw swelling | |||
| 1h | 3h | 5h | 6h | ||
| Contrast | 5 | 2.0±0.63 | 2.0±0.32 | 1.9±0.33 | 2.0±0.32 |
| Hc(12) | 5 | 2.2±0.37 | 1.8±0.42 | 1.2±0.37 | 0.9±0.33 |
| Muskrat musk (120) | 6 | 1.83±0.48 | 1.73±0.44 | 1.16±0.36 | 0.75±0.38 |
| Natural muskrat musk | 61.92±0.45 | 1.83±0.39 | 1.19±0.35 | 0.84±0.33 |
| Moschus (120) | 82.15±0.95 | 2.50±0.56 | 1.25±031 | 0.93±0.31 |
By table as seen, behind the Yu Zhiyan 6 hours, anti-inflammatory effect significantly appearred in the ip muskrat musk, and its anti-inflammatory effect and ipHc12mg/kg are suitable.
Four, muskrat musk and natural muskrat musk are to the influence of pentobarbital sodium sleep effect
Pentobarbital sodium is fastened the import packing of extra large chemical reagent factory.
Get 18 of the male mices of body weight 19.5 ± 0.26g, divide equally two groups, every day is ip muskrat musk and natural muskrat musk 120mg/kg and normal saline respectively, continuous 4 days, after the last administration 2 hours, ip pentobarbital sodium 35mg/kg, the length of one's sleep of the white mice when being recorded in 10 ℃ of room temperatures (righting reflex loss is to the time of recovering).
The result shows that distinguish 18.9 ± 10.25,26.2 ± 12.84,109.4 ± 17.93 the length of one's sleep of muskrat musk, natural muskrat musk and matched group.Muskrat musk and natural muskrat musk have remarkable shortening mice to the pentobarbital sodium effect of the length of one's sleep, and muskrat musk is shorter than the natural muskrat musk shortening time simultaneously.
Five. muskrat musk, natural muskrat musk and natural Moschus are to the influence of mice growth promoter
Give into age mice by intraperitoneal injection muskrat musk, natural muskrat musk and natural Moschus 120mg/kg, the white mice body weight obviously increases, and the young mice growth pressure was close with lumbar injection androlin 6.0mg/kg in the to the 8th to 13 day; Weightening finish difference 74.2 ± 4.5,12.1 ± 3.2,15.7 ± 5.2 is indicated stronger assimilation.In addition, when promoting children's white mice weight increase in age, also can significantly increase testis, prostate is urged seminal vesicle, and the weight of thymus and spleen promotes the growth of gonad organ and immune organ.
Six. muskrat musk, natural muskrat musk are to the antidotal influence of mice
To white mice respectively lumbar injection muskrat musk and natural muskrat musk 60mg/kg, 120mg/kg is than matched group white mice swim in low temperature (10 ℃) prolongation 2.87 and 2.77min.
Seven, the clinical research of muskrat musk oral liquid treatment apoplexy sequela, hemiplegia
The 18 routine acute initial stage paralytics similar substantially to the cause of disease, the state of an illness distinguish oral medication group 9 examples at random, matched group 9 examples, method adopt with patient's aphasis that main suit, symptom, body are looked into, the CT sheet is observed the treatment group, limb movement disturbance, headache, weak etc.All there were significant differences before and after the administration, and two groups of patients obviously are better than matched group in aspect treatment groups such as shortening aphasis, limb movement disturbance, headache, weak, cure rate, illustrate that oral medicine of the present invention has significant curative effect to the apoplexy sequela.
Eight, oral muskrat musk prevention thrombotic disease (test of vertebro-basilar artery insufficiency)
Method adopt select at random the patient with the main suit, have a medical check-up, laboratory finding is diagnosed as infull person's 40 examples of vertebral-basilar artery blood supply, carrying out administration observes, stop using all 1 weeks of interference medicament before taking medicine, and do and award after comprehensive bolt is looked into this oral every 50mg/ time, 2 times/day, did comprehensive inspection again, and defined to no effect in 14-21 days with contrast before and after the administration.The judged result standard with the main suit, have a medical check-up, have in 3 of the experimental checks that improvement person serves as effective more than 2.Otherwise be invalid, lab testing mainly contains hemorheology, platelet aggregation rate.Hemorheology blood index comprises whole blood viscosity, packed cell volume, whole blood reduced viscosity, plasma viscosity, red cell deformability, erythrocyte aggregation coefficient.
The infull person of 40 routine vertebra basilar arterial blood supplies checks after administration, and 36 examples take a turn for the better as a result, and effective percentage is 90%.
Laboratory finding before and after table 8 36 routine responder's medications (X ± SD)
| Project | Before the medication | After the medication | The P value |
| Whole blood viscosity map.s | 5.25+0.48 | 4.01+0.38 | ＜0.01 |
| Plasma viscosity map.s | 1.89+0.20 | 1.23+0.11 | ＜0.05 |
| Reduced viscosity map.s | 7.95+0.68 | 7.76+0.54 | ＞0.05 |
| Hematocrit | 0.71+0.006 | 0.49+0.05 | ＜0.01 |
| Red cell deformability | 1.28+0.19 | 0.99+0.15 | ＜0.01 |
| Erythrocyte aggregation index | 0.86+0.15 | 0.7+0.13 | ＜0.01 |
| Platelet aggregation rate % | 64.80+23.11 | 51.34+23.73 | ＜0.01 |
The above results shows that the full patient of 40 routine vertebra basilar arterial blood supplies is 90% through contrasting effective percentage with the oral 14-21 of muskrat musk of the present invention days front and back.Dizzy, nauseating, numb limbs and tense tendons, headache, cervical region sign all have clear improvement.The high blood viscosity full recovery is normal, and whole blood viscosity, hematocrit, red cell deformability, erythrocyte aggregation index obviously improve, and reduces in the normal value, and platelet aggregation rate on average descends 14.58%.Confirm that this oral medicine has anticoagulant, promotes fibrinolytic, reduces platelet aggregation rate and improves hemorheological effect.Change clinical symptoms and sign simultaneously, played the infull effect of treatment vertebra basilar arterial blood supply, reached the purpose of prevention thrombosis.
Experiment by above pharmacology shows: it is all similar to the natural Moschus with pharmacological action such as antibacterial that muskrat musk not only has the sleep of antiinflammatory, anti-pentobarbital sodium, and aspect cardiovascular, also has a similar pharmacological action, negative inotropic action, reduce the myocardial oxygen consumption effect significantly, be secondary to after the hemodynamics depression effect, the resistance of blood vessel reduces, the burden of heart alleviates, reduce the utilization of blood oxygen, this biological activity may over-burden to heart, especially comparatively favourable to preventing and treating cardiac hypertrophy and coronary heart disease.Biological activity has more similarity, and the toxicity of muskrat musk is little, has no stimulation.
Embodiment 2
Muskrat is provided by the Chinese Academy of Agricultural Sciences's man special product institute in a left side.The artificial live body of non-narcotic method is got fragrant method and is gathered natural muskrat musk, under 60 ℃ with natural muskrat musk with 3 times of 70% methanol solution saponification to the 1MKOH of muskrat musk amount, refluxed 5 hours, boil off methanol solution, be concentrated into original solution 1/3 after, add 4 times water dilution, through adding 2M H
2SO
4Acidify, pH value is controlled to be 2, and addition is 15 times the extracted with diethyl ether 5 times of solution amount, rate of extraction is 50 rev/mins, and combining extraction liquid reclaims ether with 35 ℃ of rotary evaporator evaporations, anhydrous sodium sulfate drying with 3 times of concentrated liquid measures gets total fatty acids, and its amount is 60% of natural muskrat musk amount;
Then under 20 ℃ with of the methanol-ether solution esterification of gained total fatty acids with Azimethylene .ization, used concentration ratio is 1: 9, addition is 3 times of total ester fat acid amount, refluxes 2 hours, reconcentration adds 4 times water again to 1/4 of original solution; With the extracted with diethyl ether of 15 times of solution amount to liquid colourless till, rate of extraction is 60 rev/mins, combining extraction liquid, wash with water to PH be 7, with the anhydrous sodium sulfate drying of 3 times of solution amount, the esterification material, its amount is 45% of natural muskrat musk amount.
The esterification substance dissolves in the acetone of 2 times of amounts, is added KMnO then
4Be added to till solution to color do not disappear, under 20 ℃, leave standstill and disappeared to the solution color and luster in 1 hour, in this solution, add 1MH
2SO
45 times of solid sodium sulfitees with solution amount, the control pH value is 2, be washed to PH6.8, with the extracted with diethyl ether of 12 times of amounts of solution amount 6 times, rate of extraction is 60 rev/mins, combining extraction liquid, reclaim ether with 35 ℃ of rotary evaporator evaporations, through 3 times of anhydrous sodium sulfate dryings of solution amount, get the muskrat musk active component, yield is 35%.
Embodiment 3
Muskrat is provided by the Chinese Academy of Agricultural Sciences's man special product institute in a left side.The artificial live body of non-narcotic method is got fragrant method and is gathered natural muskrat musk, alcohol-ether (1: 2) with 5 times of muskrat musk amounts extracts, most solvent is driven in evaporation, under 80 ℃ of temperature conditions, with the 80% alcoholic solution backflow of 2 times 1.5MNaOH, refluxed 8 hours, boil off alcoholic solution, be concentrated into original solution 1/2 after, add 2 times water dilution, through adding 1M HCL acidify, pH value is controlled to be 3, and the acetone with adding 10 times of solution amount extracts 8 times, rate of extraction is 30 rev/mins, combining extraction liquid reclaims acetone with 35 ℃ of rotary evaporator evaporations, through 5 times of anhydrous sodium sulfate dryings of solution amount, get total fatty acids, its amount is 80% of natural muskrat musk amount;
Under 35 ℃ of temperature conditions, the gained total fatty acids is added in the absolute methanol then, the absolute methanol volume is 8 times of total fatty acids, refluxes 3 hours, boils off most of methanol solution, and reconcentration adds 5 times water again to 1/3 of original solution; With the dichloromethane extraction of 10 times of amounts of former state amount to liquid colourless till, rate of extraction is 80 rev/mins, combining extraction liquid is washed to PH6.7, with 4 times of anhydrous sodium sulfate dryings of solution amount, the esterification material, its amount is 55% of natural muskrat musk amount.
The esterification substance dissolves in the acetone-benzene (1: 1) of 4 times of amounts, is added KMnO then
4Be added to till solution to color do not disappear, under 25 ℃, leave standstill and disappeared to the solution color and luster in 0.5 hour, in this solution, add 3MH
2SO
43 times of amount solid sodium sulfates with solution amount, pH value is 3, be washed to neutrality, with the benzene extraction of 15 times of amounts of solution amount 8 times, rate of extraction is 100 rev/mins, combining extraction liquid, reclaim benzene with 35 ℃ of rotary evaporator evaporations, 3 times of amount anhydrous sodium sulfate dryings through solution amount get the muskrat musk active component, and yield is 46%.
Embodiment 4
Muskrat is provided by the Chinese Academy of Agricultural Sciences's man special product institute in a left side.The artificial live body of non-narcotic method is got fragrant method and is gathered natural muskrat musk, first Petroleum ether extraction with 8 times of muskrat musk amounts, most solvent is driven in evaporation, under 90 ℃ of temperature conditions, with the 90% alcoholic solution backflow of 4 times 2MNaOH, refluxed 10 hours, boil off alcoholic solution, be concentrated into original solution 3/4 after, add 5 times water dilution, through adding 4M HCL acidify, pH value is controlled to be 1, and the benzene with adding 20 times of solution amount extracts 10 times, rate of extraction is 100 rev/mins, combining extraction liquid reclaims acetone with 35 ℃ of rotary evaporator evaporations, through 4 times of anhydrous sodium sulfate dryings of solution amount, get total fatty acids, its amount is 56% of natural muskrat musk amount;
Under 40 ℃ of temperature conditions, it is that 90% amount is three boron methane of 10 times of total fatty acids amounts that the gained total fatty acids is added concentration, refluxes 5 hours, boils off three boron methane then, and reconcentration adds 2 times water again to 3/4 of original solution; With the acetone extract of 20 times of solution amount to liquid colourless till, rate of extraction is 70 rev/mins, combining extraction liquid is washed to PH6.9, with 3 times of anhydrous sodium sulfate dryings of solution amount, the esterification material, its amount is 50% of natural muskrat musk amount.
Concentrated solution is dissolved in the acetone of 5 times of amounts, adds KMnO then
4Be added to till solution to color do not disappear, under 15 ℃ of room temperatures, leave standstill and disappeared to the solution color and luster in 2 hours, in this solution, add 8 times of solid carbonic acid calcium of 5M HCL and solution amount, pH value 2, be washed to neutrality, with the acetone extract of 18 times of solution amount 3 times, rate of extraction is 30 rev/mins, combining extraction liquid, reclaim ether with 35 ℃ of rotary evaporator evaporations, through 4 times of anhydrous sodium sulfate dryings of solution amount, get the muskrat musk active component, yield is 40%.
Embodiment 5
Get natural muskrat musk and put into the steam distillation device, add 400 milliliters of entry, distilled 2 hours, with the extracted with diethyl ether of 8 times of amounts 3 times, combining extraction liquid reclaims ether with 35 ℃ of rotary evaporators evaporations, getting white oily mater is muskrat musk volatility active component, and yield is 88%.
Embodiment 6
Get natural muskrat musk and put into the steam distillation device, add 300 milliliters of entry, distilled 4 hours, with the extracted with diethyl ether of 10 times of amounts 2 times, combining extraction liquid reclaims ether with 35 ℃ of rotary evaporators evaporations, getting white oily mater is muskrat musk volatility active component, and yield is 81.9%.
Embodiment 7
Get natural muskrat musk and put into the steam distillation device, add 500 milliliters of entry, distilled 5 hours, with the extracted with diethyl ether of 12 times of amounts 3 times, combining extraction liquid reclaims ether with 35 ℃ of rotary evaporators evaporations, getting white oily mater is muskrat musk volatility active component, and yield is 85.1%.
Embodiment 8
Preparation process is with embodiment 1, and is different when being saponification, and natural muskrat musk is earlier with 5 times chloroform extraction, again 70 ℃ down with the 80% methanol solution extraction of the KOH of the 0.5M of same amount, be concentrated into 2/3 then; During oxidative degradation, added acidic materials are HCL, and concentration is 2M, and pH value is 2.
Embodiment 9
Preparation process is with embodiment 1, and is different when being saponification, and natural muskrat musk is earlier with 10 times ethyl acetate extraction; During esterification reaction of organic acid, employing be 20 times absolute methanol; During oxidative degradation, added acidic materials are HCL, and concentration is 2M, and pH value is 2.
Embodiment 10
Preparation process is with embodiment 1, different is under 80 ℃ 95% methanol solution of natural muskrat musk with the 2MKOH of equivalent to be extracted, refluxed 12 hours, boil off methanol solution, be concentrated into original solution 3/4 after, add 5 times water dilution, through adding 5M HCL acidify, pH value is controlled to be 3,18 times extracted with diethyl ether of reuse solution amount 10 times, rate of extraction is 100 rev/mins, combining extraction liquid reclaims ether with 35 ℃ of rotary evaporator evaporations, with the anhydrous sodium sulfate drying of 5 times of concentrated liquid measures, get total fatty acids, its amount is 58% of natural muskrat musk amount;
Then under 30 ℃ with the gained total fatty acids with three boron methane esterifications, addition is 12 times of total ester fat acid amount, refluxes 5 hours, reconcentration adds 5 times water again to 1/2 of original solution; With the benzene of 15 times of solution amount be extracted to liquid colourless till, rate of extraction is 40 rev/mins, combining extraction liquid, wash with water to PH be 7, with the anhydrous sodium sulfate drying of 3 times of solution amount, the esterification material, its amount is 46% of natural muskrat musk amount.
The esterification substance dissolves in the acetone-benzene of 5 times of amounts, is added KMnO then
4Be added to till solution to color do not disappear, under 15 ℃, leave standstill and disappeared to the solution color and luster in 2 hours, in this solution, add 1MH
2SO
48 times of solid calcium sulphate with solution amount, the control pH value is 3, be washed to PH6.5, with the acetone extract of 12 times of amounts of solution amount 10 times, rate of extraction is 80 rev/mins, combining extraction liquid, reclaim ether with 35 ℃ of rotary evaporator evaporations, through 3 times of anhydrous sodium sulfate dryings of solution amount, get the muskrat musk active component, yield is 38%.
Although the present invention has been done detailed explanation and has quoted some instantiations as proof, for a person skilled in the art, only otherwise leave that the spirit and scope of the present invention can be done various variations or correction is obvious.
Claims (14)
1. muskrat musk active component is characterized in that comprising fatty acid and esters, macrocyclic ketone and the steroidal class composition of carbon to two 18 carbon, and the preparation technology of this muskrat musk active component may further comprise the steps:
1. it is an amount of) to get natural muskrat musk, carries out saponification with alkaline alcohol solution, concentrates the back thin up, after the strong acid acidify, and with solvent extraction extraction, combining extraction liquid, dry total fatty acids;
2.) with the gained total fatty acids, behind esterification reaction of organic acid,, be washed to neutrality with the solvent extraction extraction, drying gets the esterification material;
3.) concentrated solution is dissolved in acetone or the acetone-benzene, oxidizer is carried out oxidative degradation then, adds the acidic materials acidify after leaving standstill, and is washed to neutrality, and extracts with solvent extraction, the dry muskrat musk active component that gets.
2. according to the described a kind of muskrat musk active component of claim 1, it is characterized in that the content of described muskrat musk active component is:
C
1-C
28Fatty acid and esters 50%-80% thereof
Macrocyclic ketone 18%-45%
Steroidal class 1%-5%.
3. according to the described a kind of muskrat musk active component of claim 1, it is characterized in that described muskrat musk active component also contains aminoacid, total nitrogen content is 0.5%-1%; Described aminoacid can be aspartic acid, threonine, serine, glutamic acid, proline, liver propylhomoserin, alanine, methionine, isoleucine, leucine, lysine.
4. according to the described a kind of muskrat musk active component of claim 1, the temperature that it is characterized in that the saponification described in the step 1) is 60 ℃～90 ℃, described alkaline alcohol solution is for containing alkaline 60%～95% methanol of 0.5M～2M or alcoholic solution, described highly basic can be KOH or NaOH, addition is 1～4 times of natural muskrat musk, and the described saponification time is 3～12 hours; Described concentrated back thin up adds 2～5 times water of concentrated solution again for to be concentrated into 1/3～3/4 of original solution earlier; Described strong acid is H
2SO
4Or HCl, concentration is 1M～5M, adjusting pH value is 1～4; The extraction solvent for use is ether, acetone or dichloromethane or benzene, and extraction times is 3～10 times, and each addition is 10～20 times of natural muskrat musk; Mixing speed during extraction is 20～100 commentaries on classics/per minutes, and the amount of the total fat of dry back gained is the 40%-80% of natural muskrat musk.
5. according to the described a kind of muskrat musk active component of claim 1, it is characterized in that step 2) described in the esterification reaction of organic acid temperature be 15 ℃～40 ℃, can adopt the methanol-ether solution esterification of Azimethylene .ization, used concentration is 1～5: 9～15, addition is 1.5～5 times of total fatty acids amount, the return time of esterification reaction of organic acid is 1～5 hour, also can adopt concentration is that the addition of 90%-100% is 5～10 times the absolute methanol or the three boron methane of total fatty acids amount, after most solutions is removed in steaming, be concentrated into 1/4～3/4 of original solution, add 2～5 times water dilution of concentrated solution again; The extraction solvent for use is ether, acetone, dichloromethane or benzene, addition is 8～20 times of solution amount, be extracted to liquid colourless till, combining extraction liquid, be washed to neutrality, with 3～5 times of anhydrous sodium sulfate dryings of solution amount, dry back gained esterification amount of substance is the 30%-60% of natural muskrat musk.
6. according to the described a kind of muskrat musk active component of claim 1, the addition that it is characterized in that the acetone described in the step 3) or acetone-benzene is 2～5 times of esterification amount, and the concentration ratio of described acetone-benzene is 1: 1, and described oxidant is KMnO
4, addition is 1～2 times KMnO
4, the solution purple is not disappeared till; Left standstill 0.5～2 hour under 15 ℃～25 ℃ conditions, described acidic materials are H
2SO
4Or HCL, control PH1～3, H
2SO
4Addition be 1～10 times of solution amount, concentration is 0.5～5M; Be washed to neutrality, the extraction solvent for use is ether, acetone, dichloromethane or benzene, and extraction times is 3～10 times, and each addition is 10～20 times of solution amount; The amount of dry back gained muskrat musk active component is 30%～55%.
7. according to the described a kind of muskrat musk active component of claim 1, it is characterized in that getting natural muskrat musk adopts the vapor distillation method distillation after 1～5 hour, ether, acetone, dichloromethane solvent extraction with 8～15 times of former states extract 1～5 time, remove solvent, drying, getting white oily mater is the volatile active component of muskrat musk.
8. the preparation technology of a muskrat musk active component, this technology may further comprise the steps:
1. it is an amount of) to get natural muskrat musk, carries out saponification with alkaline alcohol solution, concentrates the back thin up, after the strong acid acidify, and with solvent extraction extraction, combining extraction liquid, dry total fatty acids;
2.) with the gained total fatty acids, behind esterification reaction of organic acid,, be washed to neutrality with the solvent extraction extraction, drying gets the esterification material;
3.) concentrated solution is dissolved in acetone or the acetone-benzene, oxidizer is carried out oxidative degradation then, adds the acidic materials acidify after leaving standstill, and is washed to neutrality, and extracts with solvent extraction, the dry muskrat musk active component that gets.
9. the preparation technology of described according to Claim 8 a kind of muskrat musk active component, the temperature that it is characterized in that the saponification described in the step 1) is 60 ℃～90 ℃, described alkaline alcohol solution is for containing alkaline 60%～95% methanol of 0.5M～2M or alcoholic solution, described highly basic can be KOH or NaOH, addition is 1～4 times of natural muskrat musk, and the described saponification time is 3～12 hours; Described concentrated back thin up adds 2～5 times water of concentrated solution again for to be concentrated into 1/3～3/4 of original solution earlier; Described strong acid is H
2SO
4Or HCl, concentration is 1M～5M, adjusting pH value is 1～4; The extraction solvent for use is ether, acetone or dichloromethane or benzene, and extraction times is 3～10 times, and each addition is 10～20 times of natural muskrat musk; Mixing speed during extraction is 20～100 commentaries on classics/per minutes, and the amount of the total fat of dry back gained is the 40%-80% of natural muskrat musk;
10. the preparation technology of described according to Claim 8 a kind of muskrat musk active component, it is characterized in that step 2) described in the esterification reaction of organic acid temperature be 15 ℃～40 ℃, can adopt the methanol-ether solution esterification of Azimethylene .ization, used concentration is 1～5: 9～15, addition is 1.5～5 times of total fatty acids amount, the return time of esterification reaction of organic acid is 1～5 hour, also can adopt concentration is that the addition of 90%-100% is 5～10 times the absolute methanol or the three boron methane of total fatty acids amount, after most solutions is removed in steaming, be concentrated into 1/4～3/4 of original solution, add 2～5 times water dilution of concentrated solution again; The extraction solvent for use is ether, acetone, dichloromethane or benzene, addition is 8～20 times of solution amount, be extracted to liquid colourless till, combining extraction liquid, be washed to neutrality, with 3～5 times of anhydrous sodium sulfate dryings of solution amount, dry back gained esterification amount of substance is the 30%-60% of natural muskrat musk.
11. the preparation technology of described according to Claim 8 a kind of muskrat musk active component, the addition that it is characterized in that the acetone described in the step 3) or acetone-benzene is 2～5 times of esterification amount, the concentration ratio of described acetone-benzene is 1: 1, and described oxidant is KMnO
4, addition is 1～2 times KMnO
4, the solution purple is not disappeared till; Left standstill 0.5～2 hour under 15 ℃～25 ℃ conditions, described acidic materials are H
2SO
4Or HCL, control PH1～3, H
2SO
4Addition be 1～10 times of solution amount, concentration is 0.5～5M; Be washed to neutrality, the extraction solvent for use is ether, acetone, dichloromethane or benzene, and extraction times is 3～10 times, and each addition is 10～20 times of solution amount; The amount of dry back gained muskrat musk active component is 30%～55%.
12. the preparation technology of described according to Claim 8 a kind of muskrat musk active component, it is characterized in that getting natural muskrat musk adopts the vapor distillation method distillation after 1～5 hour, ether, acetone, dichloromethane solvent extraction with 8～15 times of former states extract 1～5 time, remove solvent, drying, getting white oily mater is the volatile active component of muskrat musk.
13. the application of muskrat musk active component according to claim 1 in the medicine of preparation treatment myocardial ischemia, ischemia, anticoagulant, inhibition thrombosis, coronary heart disease, vasculitis, the sleep of anti-pentobarbital sodium, growth promoter.
14. muskrat musk active component according to claim 1 is as the purposes of lasting agent, fixastive.
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| CN 03100822 CN1237972C (en) | 2003-01-22 | 2003-01-22 | Active component of muskrat fragrant, preparing technique and usage |
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