CN101874841A - Total glycosides extractive of morinda plants, as well as preparation method and application thereof - Google Patents
Total glycosides extractive of morinda plants, as well as preparation method and application thereof Download PDFInfo
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- CN101874841A CN101874841A CN2009100591049A CN200910059104A CN101874841A CN 101874841 A CN101874841 A CN 101874841A CN 2009100591049 A CN2009100591049 A CN 2009100591049A CN 200910059104 A CN200910059104 A CN 200910059104A CN 101874841 A CN101874841 A CN 101874841A
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Abstract
The invention discloses a total glycosides extractive of morinda plants, a preparation method thereof and application thereof in medicaments for treating snoring, and the weight percentage of total glycosides in the total glycosides extractive is 50-80 percent. The total glycosides extractive mainly contains the components of iridoids, such as monotropein, asperuloside and the like, morindone-6-O-beta-D-primeveroside) and the like. The preparation method comprises the following steps of: drying the morinda plants (comprising roots, stems, leaves and fruits), and crushing into 10-100meshes; carrying out reflux extraction by using petroleum ether or 6# extraction solvent oil or other organic solvents with polarity similar to that of the crushed morinda plant, and removing low-polarity components, such as essential oil and the like; heating the dregs of decoction with 20-95 percent alcohol for reflux extraction; condensing the extract, and dissolving with 10-30 percent alcohol; standing for 12 hours at 4 DEG C; removing pigment at the upper layer, carrying out vacuum condensing on the lower layer till alcohol has no odor, and processing the condensed liquid by using a macroporous resin column; washing with water to remove polysaccharide, protein and the like, eluting with 20-80 percent alcohol, and collecting the eluent; and condensing and drying to obtain the total glycosides extractive product of the morinda plants. The product of the invention is used for treating snoring (also called as Sleep apnea syndrome (SAS)), and has the advantages of quick and remarkable curative effect, no toxic or side effect, low price, convenient use and the like.
Description
Technical field
The present invention relates to Radix Morindae Officinalis platymiscium total glycosides extractive, and its production and use, belong to field of traditional Chinese medicine pharmacy.
Background technology
Snoring, medically be also referred to as sleep apnea syndrome (sleep apnea syndrome, SAS), be commonly encountered diseases and the frequently-occurring disease of just being paid close attention to gradually in recent years, be asphyxia and the low ventilation that between sleep period, takes place repeatedly, cause repeatedly waking up between sleep period with awake and cause hypoxia to take place, be comparatively common clinically a kind of sleep illness.SAS is that a kind of state relies on (state-dependent) syndrome, since its easy trouble factor as fat, go up the air flue anatomical structure muscular tension that can the generation state relies on such as narrow and reduce, the result causes air flue to subside repeatedly, its spectrum of disease is described as: beginning is Primary snoring (pharyngeal vibration), and then flow limitation (low ventilation) appears, complete respiratory arrest (asphyxia) appears at last.Its cardinal symptom is snoring, the observed asphyxia of energy and over-drastic daytime sleepiness.Hypoxemia, the sympathetic impulsion of sending repeatedly, heart burden take place, the brain microarousal occurs repeatedly in physiology result at once; Need microarousal to recover airway open, the result causes depriving of serious sleep fragment and sleep.Fa Zuo asphyxia and low ventilation repeatedly, cause the hypoxia, high carbon acid and the acidemia that show effect repeatedly, cause histoorgan ischemia, anoxia, and then cause many organs multisystem functional defect or obstacle gradually, the process of meeting accelerated ageing, having sizable potential danger, is the common pathologic basis of other numerous disease.Snoring can cause hyperemia, edema and the inflammatory reaction of pharyngeal soft tissue during sleep, increases the weight of obstructive apnea.This disease male pilosity, and the state of an illness is heavier, based on asphyxia; Female patient is particularly easily suffered from this disease after the menopause, but be light than the male, more be prone to wake up after symptoms such as headache, anxiety, depression.
Therapeutic Principle to SAS is: etiological treatment, keep respiratory passage unblocked, prevent and treat complication.Nasal continuous positive airway pressure (nCPAP) is still the Therapeutic Method of the most reliable maintenance respiratory passage unblocked so far, but owing to the therapeutic equipment costliness, carry factor such as inconvenience, the following SAS patient of most of moderates and moderate does not all accept the treatment of nCPAP; With device for preventing snoring, mouthpart (effect of spatula sample does not allow and falls behind the root of the tongue) treatment, the patient is difficult to be adapted to; The operative treatment complexity, complication, easily recurrence, and expense height are arranged.Drug therapy yes most convenient, therefore people are exploring the method for Drug therapy always, several Western medicine once appearred, as acetazolamide, peace palace body ketone, theophylline class medicine, cerebral cortex stimulant opiates, blood pressure lowering class and act on the medicine etc. of psychiatric system, these medicines have certain therapeutical effect, but that shortcoming is side effect is very big.The red careless snoring granule of compound Chinese medicinal preparation is domestic present unique treatment accurate font size medicine of snoring, but price is expensive, the textual criticism of yet having no way of now of its actual therapeutic effect.In a word, at sleep apnea syndrome, the present clinical medicine evident in efficacy, that side effect is little, cheap, easy to use that still lacks.
The Rubiaceae Radix Morindae Officinalis belongs to (Morinda Linn.) plant 80 kinds approximately in the whole world, all originate in the torrid areas, maximum with Asia and Oceania especially, America and African less product.In China 12 kinds and 2 mutation are arranged approximately, common have a Radix Morindae Officinalis M.officinalisHow, false crust halberd M.shuhuaensis C.Y.Chen et M.S.Huang, Morinda Citifolia M.citrifolia L., Radix Morindae Umbellatae M.umbellata L. etc., mainly be distributed in the west and south to the southeast, and Taiwan and area, Hong Kong.What the domestic and international record of Radix Morindae Officinalis platymiscium can be used as medicine has 8 kinds, and its medicinal part is mainly root, leaf, and mostly is the folk tradition medication, has effects such as wind-damp dispelling, cough-relieving, hemostasis, parasite killing.
The Chinese medicine Radix Morindae Officinalis, have another name called Intestinum Gallus domesticus wind, Herba Morindae Parvifoliae, triangle vine etc., for the Rubiaceae Radix Morindae Officinalis belongs to the perennial dry root of climbing up by holding on to bejuco Radix Morindae Officinalis (Morinda officinalis How), mainly being distributed in the torrid zone and the subtropical zone of provinces and regions such as Guangdong, Guangxi, Fujian, Hainan, is one of four famous Da Nan medicines of China.Radix Morindae Officinalis sweet in the mouth, suffering, slightly warm in nature has the effect of kidney-replenishing, bone and muscle strengthening, wind-damp dispelling.The Radix Morindae Officinalis beginning is stated from Shennong's Herbal, and the book on Chinese herbal medicine that China's successive dynasties publish all has record, and the Pharmacopoeia of the People's Republic of China is gone through version from version in 1963 and all recorded this kind.Radix Morindae Officinalis be health ministry announce can be used for one of article of health food.
Radix Morindae Officinalis has pharmacological actions such as defying age, enhance immunity, endocrine regulation, promotion hemopoietic, antidepressant, antitumor, antiinflammatory and analgesia as traditional the kidney invigorating good medicine.With the Radix Morindae Officinalis is one of composition, has now developed capsule of Baji, crust halberd tonic wine, crust halberd the kidney invigorating ball, Fructus Lycii 'Baji ' wine, crust halberd oral liquid, sea-horse and morinda root capsule, the crust halberd compound preparations such as positive capsule that shake, is mainly used in the kidney invigorating, regulating menstruation etc.
There are long Radix Morindae Officinalis plantation history and medicinal history in China, but the root of the at present domestic Radix Morindae Officinalis rattan in 5～10 years of growth of mainly gathering, its stem, leaf resource then waste.The Philippine scientist finds that the Radix Morindae Officinalis leaf extract has stronger anti-mycobacterium tuberculosis effect, and its mechanism of action may be different fully with existing various chemosynthesis antituberculosis drugses, among this novel antituberculosis drugs is being studied at present.The Radix Morindae Officinalis leaf is very large, the output height, and growth belongs to a kind of " renewable plant resources " rapidly.The present invention extracts the treatment that Radix Morindae Officinalis platymiscium total glycosides is used for snoring, and this is for utilizing Chinese material medicine resource to have positive effect better.
The Radix Morindae Officinalis platymiscium contains chemical constituents such as saccharide, iridoid glycosides, monoterpene glycosides, anthraquinone and glycoside thereof, aminoacid, lipid, organic acid and trace element.Up to now, Radix Morindae Officinalis platymiscium total glycosides extractive is used for the treatment of in the product of sleep apnea syndrome (snoring), does not still have pertinent literature record or research report both at home and abroad.
Summary of the invention
The object of the present invention is to provide a kind of Radix Morindae Officinalis platymiscium total glycosides extractive, and its production and use.
At first, the invention provides a kind of Radix Morindae Officinalis platymiscium total glycosides extractive, wherein the percentage by weight of total glycosides is 50%～80%.
Wherein, described Radix Morindae Officinalis platymiscium total glycosides extractive obtains by extracting in the Radix Morindae Officinalis platymiscium Morinda Linn. herb (comprise root, stem, leaf, really).
Specifically, be from Radix Morindae Officinalis Morinda officinalis How, southwest crust halberd Morinda scabrifolia Y.Z.Ruan, false crust halberd Morinda shuhuaensis C.Y.Chen et M.S.Huang, Hubei crust halberd Morinda hupehensis S.Y.Hu, Morinda Citifolia Morinda citrifolia L., Hainan crust halberd Morinda hainanensis Merr.et How extracts acquisition among the Radix Morindae Umbellatae Morindaumbellata L..
This total glycosides extractive contains one or more glycoside monomers with chemical constitution as follows:
Wherein 1,2,3,5,6 is iridoid glycosides, and 4 is a monoterpene glycoside, and 7 is an anthraquinone glycoside.
Secondly, the invention provides the preparation method of Radix Morindae Officinalis platymiscium total glycosides extractive, may further comprise the steps:
(1) removes volatile oil: will be crushed to 10～100 orders after Radix Morindae Officinalis platymiscium (comprising root, stem, leaf and the fruit) oven dry, with low polar organic solvent reflux, extract,, raw material and extractant w/v are 1: 5～20, extract 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, extract is mainly volatilization wet goods low polarity component, discards;
(2) ethanol water extracts, concentrates: will be through the medicinal residues of the Radix Morindae Officinalis platymiscium after (1) removes volatile oil with 20%～95% ethanol extraction with the method for reflux, raw material and extractant w/v are 1: 5～20, extract 3 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure gets ethanol extraction;
(3) depigmentation: add 10%～30% ethanol of 3～5 times of weight in above-mentioned ethanol extraction, dissolving, 4 ℃ were left standstill 12 hours, removed the upper strata pigment, and lower floor is evaporated to no ethanol and distinguishes the flavor of;
(4) resin absorption, eluting, concentrate: macroporous resin column on the solution of extract that will obtain through (3), wash with water earlier and remove polysaccharide, protein etc., use 20%～80% ethanol elution then, collect eluent, after concentrated, drying, obtain Radix Morindae Officinalis platymiscium total glycosides extractive product.
The used low polar organic solvent of step (1) can be a petroleum ether, 6
#At least a in solvent for extraction, hexane, heptane, chloroform, ethyl acetate, the acetone.
Macroporous resin in the step (4) is selected from each model such as HPD-100, HPD-200A, HPD-200B, HPD-300, HPD-700, HPD-417, HPD-427, HPD-722, HPD-500, HPD-600, HPD-826, ADS-17, ADS-7, AB-8, D-101, preferably HPD-100 type, ADS-17 type and D-101 type.
Provide the content assaying method (spectrophotography) of total glycosides in the Radix Morindae Officinalis platymiscium total glycosides extractive below:
(1) preparation of reference substance solution
Get monotropein 10.0mg and place the 10mL volumetric flask, the accurate title, decide, and the adding distil water standardize solution shakes up, and promptly gets (every 1mL contains monotropein 1.02mg).
(2) preparation of need testing solution
Precision takes by weighing the Radix Morindae Officinalis platymiscium total glycosides extractive sample 0.1g that is dried to constant weight, changes over to fully in the 25mL volumetric flask, and adding distil water dissolving, standardize solution are as need testing solution.
(3) color condition
Get 0.05～0.50mL liquid to be measured in the 5mL volumetric flask, 75% ethanol adds to 2mL, adds 1mL 50%HCl, shake up, 80 ℃ of hydrolysis 20min take out, cooling immediately, adding 1mL paradime thylaminobenzaldehyde solution (dimethylaminobenzaldehyde 0.525g adds the 75mL glacial acetic acid, 30mL water, promptly), with 75% ethanol standardize solution, shake up, room temperature is placed 30min, and 620nm uses at the place spectrophotometric determination solution absorbance.
(4) standard curve is drawn
Get reference substance solution (1.02mg/mL) 0.05,0.10,0.15,0.20,0.25,0.30,0.35mL, according to (a 3) colour developing, the 620nm place measures absorbance, is respectively 0.0303,0.0614,0.0910,0.1177,0.1489,0.1755,0.1962.(C, μ g) is abscissa with reference substance content, and trap (A) is a vertical coordinate, and the calculating regression equation is A=0.002744C+0.005314, r=0.999.
(5) sample size is measured
The accurate need testing solution 0.2mL that draws according to (a 3) colour developing, measures trap, asks need testing solution concentration according to regression equation, the content of total glycosides in the calculation sample.
Further, the invention provides the application of this Radix Morindae Officinalis platymiscium total glycosides extractive in the medicine of preparation treatment snoring or sleep apnea syndrome (SAS), be included in the application in the diseases such as central respiratory arrest syndrome (CSAS), obstructive apnea syndrome (OSAS) and MA syndrome.
Further, the invention provides a kind of pharmaceutical composition, be that Radix Morindae Officinalis platymiscium total glycosides extractive by effective dose is an active component, add the medicament that acceptable accessories or complementary composition are prepared from, comprise oral formulations and injection preparation, oral formulations comprises tablet, capsule, soft capsule, granule, drop pill etc., and injection preparation comprises injection, powder ampoule agent for injection etc.
At last, the present invention also provides a kind of Halth-care composition, is that the Radix Morindae Officinalis platymiscium total glycosides extractive with effective dose is an active component, adds the health product oral formulations that acceptable accessories or complementary composition are prepared from.
The specific embodiment of form by the following examples, foregoing invention content of the present invention is described in further details, but should not be construed as summary of the invention of the present invention and only limit to following examples, all inventions of making based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
The preparation of embodiment 1 Radix Morindae Officinalis herb total glycosides extractive
Get Radix Morindae Officinalis (Morinda officinalis How) the plant herb 1000g of oven dry, be crushed to 10～100 orders, with 6
#Solvent for extraction 10L reflux, extract, 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims solvent naphtha, and extract is mainly volatilization wet goods low polarity component, discards; To go the medicinal residues behind the volatile oil to extract with 70% ethanol 10L with the method for reflux, the time is 2 hours, carries altogether 3 times, and merge extractive liquid,, concentrating under reduced pressure get ethanol extraction 157g; Use this extract of 20% dissolve with ethanol of 4 times of weight then, 4 ℃ leave standstill 12 hours after, remove uvea (upper strata), lower floor is evaporated to no ethanol flavor, last D-101 macroporous resin column, wash with water earlier and remove polysaccharide, protein etc., use 50% ethanol elution then, collect eluent, after concentrated, drying, obtain Radix Morindae Officinalis herb total glycosides extractive product 39g, after testing, total glycosides content 80% wherein.
The preparation of embodiment 2 Morinda Citifolia herb total glycosides extractives
Get Morinda Citifolia (Morinda citrifolia L.) the plant herb 1000g of oven dry, be crushed to 10～100 orders, use petroleum ether 5L reflux, extract, 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims petroleum ether, extract is mainly volatilization wet goods low polarity component, discards; To go the medicinal residues behind the volatile oil to extract with 20% ethanol 20L with the method for reflux, the time is 2 hours, carries altogether 3 times, and merge extractive liquid,, concentrating under reduced pressure get ethanol extraction 166g; Use this extract of 10% dissolve with ethanol of 3 times of weight then, 4 ℃ leave standstill 12 hours after, remove uvea (upper strata), lower floor is evaporated to no ethanol flavor, last HPD-500 macroporous resin column, wash with water earlier and remove polysaccharide, protein etc., use 80% ethanol elution then, collect eluent, after concentrated, drying, obtain Morinda Citifolia herb total glycosides extractive product 45g, after testing, total glycosides content 50% wherein.
The preparation of embodiment 3 false crust halberd herb total glycosides extractives
Get vacation crust halberd (Morinda shuhuaensis C.Y.Chen et M.S.Huang) the plant herb 1000g of oven dry, be crushed to 10～100 orders, with acetone 20L reflux, extract, 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims acetone, and extract is mainly volatilization wet goods low polarity component, discards; To go the medicinal residues behind the volatile oil to extract with 95% ethanol 5L with the method for reflux, the time is 2 hours, carries altogether 3 times, and merge extractive liquid,, concentrating under reduced pressure get ethanol extraction 146g; Use this extract of 30% dissolve with ethanol of 5 times of weight then, 4 ℃ leave standstill 12 hours after, remove uvea (upper strata), lower floor is evaporated to no ethanol flavor, last ADS-17 macroporous resin column, wash with water earlier and remove polysaccharide, protein etc., use 20% ethanol elution then, collect eluent, through concentrating, obtaining the false halberd herb total glycosides extractive product 37g that clings to after the drying, after testing, total glycosides content 64% wherein.
The separation of 4 seven glycoside monomers of embodiment (chemical compound 1～7)
Get Radix Morindae Officinalis platymiscium total glycosides extractive 5g (embodiment 1 makes), last XAD-2 macroporous resin column, successively water and methanol-eluted fractions concentrate respectively, obtain water elution thing 4.1g, methanol-eluted fractions thing 0.8g.The methanol-eluted fractions thing is carried out silica gel column chromatography (CHCl successively
3-MeOH-H
2O system eluting), Chromatorex-ODS DM1020T chromatographic column is separated (50%MeOH eluting) and is partly prepared HPLC and separate (YMC Pack S-5 120A chromatographic column, 60%MeOH makes mobile phase), obtain asperuloside (1) (10.5mg), Radix Morindae Officinalis glycoside (morofficinaloside, 2) (5.2mg), asperuloside acid (3) (3.5mg) and l-baras camphor-O-[β D-celery glycosyl (1 → 6)]-O-β-D-glucopyanoside (4) (8.3mg); The water elution thing is carried out Chromatorex-ODS DM1020T chromatographic column successively separate (H
2O-MeOH system eluting), silica gel column chromatography (CHCl
3-MeOH-H
2O system eluting) with partly prepare HPLC and separate (YMC Pack S-5120A chromatographic column, 10%MeOH makes mobile phase), obtain monotropein (5) (2.01g), deacetylasperulosidic acid (6) (1.82g), morindone-6-O-β-D-primveroside (7) is (0.116g).
Asperuloside (1): colourless very brilliant; 185～186 ℃ of mp, ESI-MS m/z (%): 437[M+Na]
+, 413[M-H]
-, 275[M+Na-Glc]
+.
1H-NMR (DMSO-d
6, 600MHz) δ: 7.39 (1H, d, J=2.0Hz, H-3), 5.81 (1H, s, H-1), 5.70 (1H, s, H-7), 5.54 (1H, d, J=6.5Hz, H-6), 4.66 (2H, dd, J=0.90,15.0Hz, AB system, H-10), 4.50 (1H, d, J=7.5Hz, H-1 '), 3.70 (1H, dd, J=1.5,12.0Hz, H-6 '), 3.54 (1H, td, J=2.0,7.0Hz, H-5), 3.43 (1H, dd, J=6.5,12.0Hz, H-6 '), 3.21 (1H, m, H-9), 3.14～3.17 (2H, m, H-3 ', 5 '), 3.03 (1H, t, J=9.5Hz, H-4 '), 2.97 (1H, dd, J=8.0,7.5Hz, H-2 '), 2.01 (3H, s, H-CH
3).
13C-NMR (DMSO-d
6, 150MHz) δ: 91.9 (C-1), 149.3 (C-3), 105.2 (C-4), 36.4 (C-5), 84.7 (C-6), 127.8 (C-7), 143.3 (C-8), 44.2 (C-9), 61.1 (C-10), 170.2 (C-11), 21.2 (CH
3), 170.6 (AcO), 99.1 (C-1 '), 73.7 (C-2 '), 77.1 (C-3 '), 70.7 (C-4 '), 78.0 (C-5 '), 61.8 (C-6 ').
Radix Morindae Officinalis glycoside (Morofficinaloside) (2): white powder,
(c=0.26, MeOH); HRESI-MS:m/z 405.1394[M-H]
-(calcd.for C
17H
25O
11, 405.1497); UV (MeOH) λ
Max(log ε): 235 (5.08) nm; IR (KBr): 3400,1700,1632,1078cm
-1 1H-NMR (D
2O, 600MHz) δ: 1.48 (1H, ddd, J=5.0,9.1,13.9Hz, 6 β-H), 1.95 (1H, m, 9-H), 1.96 (1H, m, 8-H), 2.05 (1H, m, 6 α-H), 2.92 (1H, m, 5-H), 3.06-3.65 (all 6H, sugar protons), 3.53 (3H, s, carbomethoxyl), 3.55 (1H, m), 3.70 (brd, J=10.6Hz, 10-H
2), 4.15 (1H, m, 7-H), 4.63 (1H, d, J=8.9Hz, 1 '-H), 5.09 (1H, d, J=4.6Hz, 1-H), 7.30 (1H, s, 3-H).
13C-NMR (D
2O, 150MHz) δ: 98.5 (C-1), 152.6 (C-3), 112.9 (C-4), 31.8 (C-5), 41.5 (C-6), 72.6 (C-7), 48.3 (C-8), 41.8 (C-9), 61.3 (C-10), 170.9 (C-11), 52.6 (OCH
3), 99.7 (C-1 '), 73.5 (C-2 '), 76.5 (C-3 '), 70.3 (C-4 '), 77.0 (C-5 '), 61.4 (C-6 ').
Asperuloside acid (3): pale yellow powder, vanillin-concentrated sulphuric acid reagent show sky blue.The inspection of acid hydrolysis thin layer is known, and contained sugar is glucose.ESI-MS：m/z：433[M+H]
+，455[M+Na]
+；
1H-NMR(CD
3OD，600MHz)δ：7.66(1H，d，J＝0.8Hz，H-3)，6.03(1H，s，H-7)，5.06(1H，d，J＝9.1Hz，H-1)，4.73(1H，d，J＝7.8Hz，H-1′)，4.67(2H，dd，J＝0.9，15.0Hz，AB?system，H-10)，3.86(1H，d，J＝12.2Hz，H-6′a)，3.64(1H，dd，J＝5.3，12.1Hz，H-6′b)，3.23～3.43(5H，m，H-6，2′，3′，4′，5′)，3.03(1H，m，H-5)，2.57(1H，t，J＝8.2Hz，H-9)，2.01(3H，s，CH
3)；
13C-NMR(CD
3OD，150MHz)δ：170.6(AcO)，169.5(C-11)，155.5(C-3)，151.5(C-8)，129.9(C-7)，108.3(C-4)，101.6(C-1)，100.5(C-1′)，78.5(C-3′)，77.9(C-5′)，75.5(C-6)，75.0(C-2′)，71.7(C-4′)，62.9(C-6′)，61.7(C-10)，45.9(C-9)，42.7(C-5)，21.2(CH
3)。
L-baras camphor-O-[β-D-celery glycosyl-(1 → 6)]-O-β-D-glucopyanoside (4): colourless acicular crystal (EtOH-H
2O), mp is 183～185 ℃; Elementary analysis: measured value C 55.69, H 8.00 (C
21H
36O
10, value of calculation C 56.23, H 8.09);
(c=0.6, MeOH), IR v
MaxCm
-1: 3400,2950～2880,1100～1000,
1H-NMR (C
5D
5N, 600MHz) δ: 0.78 (3H, s, H-10), 0.83 (3H, s, H-9), 1.02 (3H, s, H-1), 4.74 (1H, d, J=7.3Hz, H-1 '), 5.69 (1H, d, J=2.0Hz, H-1 ").
13C-NMR (C
5D
5N, 150MHz) δ: 14.1 (C-1), 49.9 (C-2), 27.2 (C-3), 28.6 (C-4), 45.6 (C-5), 38.0 (C-6), 86.1 (C-7), 47.7 (C-8), 19.0 (C-9), 19.9 (C-10), 105.7 (C-1 '), (75.3 C-2 '), 78.5 (C-3 '), 71.9 (C-4 '), 77.0 (C-5 '), (68.7 C-6 '), 110.9 (C-1 "), 77.9 (C-2 "), 80.3 (C-3 "), 74.9 (C-4 "), 66.0 (C-5).
Monotropein (5): white needle (MeOH-H
2O); ESI-MS m/z:413[M+Na]
+ 1H-NMR (D
2O, 600MHz) δ: 7.47 (1H, s, H-3), 6.29 (1H, dd, J=5.5,3.0Hz, H-6), 5.74 (1H, d, J=5.5,1.5Hz, H-7), 5.67 (1H, d, J=1.5Hz, H-1), (4.83 1H, d, J=8.0Hz, H-1 '), 2.74 (1H, dd, J=2.0,8.5Hz, H-9);
13C-NMR (D
2O, 150MHz) δ: 171.6 (C-11), 152.7 (C-3), 138.2 (C-6), 133.0 (C-7), 111.2 (C-4), (99.3 C-1 ofGlc), 95.3 (C-1), 85.8 (C-8), (77.4 C-5 of Glc), 76.7 (C-3 of Glc), 73.8 (C-2 of Glc), (70.7 C-4 ofGlc), 67.5 (C-10), 61.8 (C-6 of Glc), 45.1 (C-9), 38.1 (C-5).
10-deacetyl asperulosidic thuja acid (6): pale yellow powder, vanillin-concentrated sulphuric acid reagent show sky blue.The inspection of acid hydrolysis thin layer is known, and contained sugar is glucose.ESI-MS：m/z：391[M+H]
+，413[M+Na]
+；
1H-NMR(CD
3OD，600MHz)δ：7.65(1H，d，J＝0.8Hz，H-3)，6.02(1H，s，H-7)，5.05(1H，d，J＝9.2Hz，H-1)，4.72(1H，d，J＝7.8Hz，H-1′)，4.45(1H，d，J＝16.0Hz，H-10a)，4.21(1H，d，J＝16.0Hz，H-10b)，3.85(1H，d，J＝12.0Hz，H-6′a)，3.63(1H，dd，J＝5.2，12.0Hz，H-6′b)，3.22～3.42(5H，m，H-6，2′，3′，4′，5′)，3.02(1H，m，H-5)，2.56(1H，t，J＝8.0Hz，H-9)；
13C-NMR(CD
3OD，150MHz)δ：169.4(C-11)，155.4(C-3)，151.4(C-8)，129.8(C-7)，108.2(C-4)，101.5(C-1)，100.4(C-1′)，78.4(C-3′)，77.8(C-5′)，75.4(C-6)，74.9(C-2′)，71.6(C-4′)，62.8(C-6′)，61.6(C-10)，45.8(C-9)，42.6(C-5)。
Morindone-6-O-β-D-primveroside (7): yellow needle,
(c=0.3, MeOH/H
2O); IR v
MaxCm
-1: 3350,1628,1603,1450,1423,1371,1261,1246,1057,991; UV (MeOH) λ
Max(log ε): 260 (4.56), 230 (4.61);
1H-NMR (600MHz, CD
3OD) δ: 12.92 (1H, s, 1-OH), 7.50 (1H, d, J=7.8Hz, H-3), 7.45 (1H, d, J=7.8Hz, H-4), 12.70 (1H, s, 5-OH), 7.54 (1H, d, J=8.6Hz, H-7), 7.64 (1H, d, J=8.6Hz, H-8), 2.18 (3H, s, H-11), 5.08 (1H, d, J=7.2Hz, H-1 '), 2.93～4.00 (6H, H-2 ', 3 ', 4 ', 5 ', 6 '), 4.15 (1H, d, J=7.4Hz, H-1 "), 2.93～4.00 (5H, H-2 ", 3 ", 4 " and, 5 ");
13C-NMR (150MHz, CD
3OD) δ: 160.2 (C-1), 135.1 (C-2), 137.0 (C-3), 118.6 (C-4), 130.5 (C-4a), 152.1 (C-5), 151.6 (C-6), 120.5 (C-7), 120.5 (C-8), 125.2 (C-8a), 186.8 (C-9), 114.5 (C-9a), 187.4 (C-10), 115.8 (C-10a), 15.7 (C-11), (99.8 C-1 '), 73.1 (C-2 '), 76.5 (C-3 '), (69.6 C-4 '), (76.6 C-5 '), 68.4 (C-6 '), 104.1 (C-1 "); 73.5 (C-2 "), 76.1 (C-3 "), 69.5 (C-4 "), 65.6 (C-5 ").
Embodiment 5 preparation tablets
With Radix Morindae Officinalis platymiscium total glycosides extractive 100g of the present invention (embodiment 1 method makes), starch 80g, dextrin 5g mix homogeneously adds 10% starch slurry system soft material, granulates with 14 order nylon screens, 60～70 ℃ of aeration-dryings, 16 mesh sieve granulate add magnesium stearate 1.5g, carboxymethyl starch sodium 5g mixing, be pressed into 1000, coating promptly.Every contains Radix Morindae Officinalis platymiscium total glycosides extractive 100mg.Become human oral every day 2 times, each 1.
The preparation of embodiment 6 capsules
Get Radix Morindae Officinalis platymiscium total glycosides extractive 100g of the present invention (embodiment 2 methods make), add starch 78g, magnesium stearate 2g mixing directly is filled to 1000 with Autocapsulefillingmachine, and polishing promptly.Become human oral every day 2 times, each 1.
The preparation of embodiment 7 drop pill
Get Radix Morindae Officinalis platymiscium total glycosides extractive 10g of the present invention (embodiment 3 methods make), drop in the polyethylene glycol 6000 of 32g heating and melting, be stirred to dissolving, be transferred in the reservoir, airtight and insulation is regulated drop pill machine drop quantitative valve at 80-90 ℃, splash into from top to bottom in 10～15 ℃ the liquid paraffin, make 1000 altogether, the ball sound of rain pattering dry doubling erasing liquor paraffin body with forming is drying to obtain.Every contains Radix Morindae Officinalis platymiscium total glycosides extractive 10mg.Become human oral every day 3 times, each 5～8.
The preparation of embodiment 8 oral liquids
Get Radix Morindae Officinalis platymiscium total glycosides extractive 10g of the present invention (embodiment 2 methods make), mix with Mel 300g, sucrose 50g, sodium benzoate 2g and distilled water 300ml, be heated to 85～90 ℃, stirring makes dissolving, and insulation 30min filters, the filtrate thin up is to 1000ml, stir evenly, embedding (every 10ml), sterilization is promptly.Become human oral every day 2 times, each 1.
The preparation of embodiment 9 granules
It is an amount of to get Radix Morindae Officinalis platymiscium total glycosides extractive 10g of the present invention (embodiment 2 methods make), dextrin 20g, sucrose 100g and ethanol, and mixing is crossed 10 mesh sieves and made granule, in 60～70 ℃ of dryings, granulate, packing is promptly, the heavy 5g of every bag becomes human oral every day 1 time, each 1 bag.
The preparation of embodiment 10 injection
Get Radix Morindae Officinalis platymiscium total glycosides extractive 50g of the present invention (embodiment 3 methods make), add water for injection and make dissolving in right amount, 0.02% the active carbon that adds amount of preparation stirs 5～10min, filter, filtrate is diluted to about 10 liters, adds sodium chloride adjusting osmotic pressure and oozes to waiting, and regulates pH7.5～8.0, ultrafiltration, embedding become 1000 (10mL/ props up).100 ℃ of 30min sterilizations promptly.Adult's vein or administered intramuscular, every day 2 times, each 1.
The preparation of embodiment 11 injectable powder
Get Radix Morindae Officinalis platymiscium total glycosides extractive 50g of the present invention (embodiment 1 method makes), add injection water and dilute sodium hydroxide and make dissolving in right amount, 0.02% the active carbon that adds amount of preparation stirs 5～10min, filter, filtrate is diluted to 1 liter, regulates pH6.5～7.8, ultrafiltration, spray drying, dry powder is promptly aseptic subpackaged.Every 100mg faces with before adding the injection water and makes dissolving in right amount, with the slowly intravenous drip of sodium chloride transfusion 250～500mL dilution back.Adult every day 2 times, each 1.
Below with the formal proof of clinical trial example beneficial effect of the present invention.
SAS patient's physical data: first group 24 examples, male 21 examples, women 3 examples, 46.5 ± 7 years old mean age; Second group 24 examples, male 19 examples, women 5 examples, 51.5 ± 4 years old mean age.All patients had not accepted any treatment, did not all have highlands inhabitation history, did not have other sleep disordered illness, be a cup too low obstacle or dementia, alcohol-free and drug dependence history.
Medication dose: the first group gives Radix Morindae Officinalis platymiscium total glycosides extractive tablet (embodiment 5 makes), and morning every day, evening respectively obey 1 (every contains Radix Morindae Officinalis platymiscium total glycosides extractive 100mg); The second group gives Radix Morindae Officinalis platymiscium total glycosides extractive oral liquid (embodiment 8 makes), and morning every day, evening respectively obey 1 (every contains Radix Morindae Officinalis platymiscium total glycosides extractive 100mg).
Monitoring method: polysomnogram (PSG) monitoring, before taking medicine and after 1 week of taking medicine, monitor respectively.
Observation index: the sound of snoring, sleep apnea index (AI), low ventilation index (HI), continuous call are inhaled time out, average asphyxia time, SaO
2, suspend and low ventilation number of times, Sleep architecture and clinical symptoms.
Statistical procedures: use the SPSS10.O statistical software and handle, the treatment cross-reference carries out the t check, and P＜0.05 is for there being significant difference.
The result:
Every respiration parameter and partial sleep parameter are shown in table 1, table 2 before and after the treatment:
PSG checks before and after the treatment of table 1 Radix Morindae Officinalis platymiscium total glycosides extractive
Sleep architecture relatively before and after the treatment of table 2 Radix Morindae Officinalis platymiscium total glycosides extractive
By table 1, table 2 as can be seen, two groups of patients of first, second after Radix Morindae Officinalis platymiscium total glycosides extractive treated for 1 week, every respiration parameter and partial sleep parameter all be improved significantly.Simultaneously, aspect the subjective symptom and the sound of snoring, all patient's sounds of snoring of treatment back obviously weaken or disappear after treatment; Suppress awake night, plays laryngalgia, giddy morning, and daytime is drowsiness, and is absent minded, and clinical symptoms such as hypomnesis all obtain improvement in various degree, and quality of life all is significantly improved.These show that all Radix Morindae Officinalis platymiscium total glycosides extractive has the good curing effect for SAS.
Claims (11)
1. Radix Morindae Officinalis platymiscium total glycosides extractive, it is characterized in that: the total glycosides percentage by weight is 50%～80%.
2. Radix Morindae Officinalis platymiscium total glycosides extractive as claimed in claim 1 is characterized in that: obtain by extracting in the Radix Morindae Officinalis platymiscium MorindaLinn. herb (comprise root, stem, leaf, really).
3. Radix Morindae Officinalis platymiscium total glycosides extractive as claimed in claim 2, it is characterized in that: from Radix Morindae Officinalis Morinda officinalisHow, southwest crust halberd Morinda scabrifolia Y.Z.Ruan, false crust halberd Morinda shuhuaensis C.Y.Chen et M.S.Huang, Hubei crust halberd Morinda hupehensis S.Y.Hu, Morinda Citifolia Morinda citrifolia L., Hainan crust halberd Morindahainanensis Merr.et How extracts acquisition in any one or a few among the Radix Morindae Umbellatae Morinda umbellata L..
4. as the described Radix Morindae Officinalis platymiscium of claim 1～3 total glycosides extractive, it is characterized in that: this extract contains one or more glycoside monomers with following chemical constitution:
Asperuloside
Radix Morindae Officinalis glycoside (morofficinaloside)
Asperuloside acid
L-baras camphor-O-[β-D-celery glycosyl-(1 → 6)]-O-β-D-pyrans Portugal
Grape glucoside (4)
Monotropein
The 10-deacetyl asperulosidic thuja acid
Morindone-6-O-β-D-primveroside (7)
5. a method for preparing as the described Radix Morindae Officinalis platymiscium of claim 1～4 total glycosides extractive is characterized in that: comprise the following steps:
(1) removes volatile oil: will be crushed to 10～100 orders after Radix Morindae Officinalis platymiscium (comprising root, stem, leaf and the fruit) oven dry, with low polar organic solvent reflux, extract,, raw material and extractant w/v are 1: 5～20, extract 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, extract is mainly volatilization wet goods low polarity component, discards;
(2) ethanol water extracts, concentrates: will be through the medicinal residues of the Radix Morindae Officinalis platymiscium after (1) removes volatile oil with 20%～95% ethanol extraction with the method for reflux, raw material and extractant w/v are 1: 5～20, extract 3 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure gets ethanol extraction;
(3) depigmentation: add 10%～30% ethanol of 3～5 times of weight in above-mentioned ethanol extraction, dissolving, 4 ℃ were left standstill 12 hours, removed the upper strata pigment, and lower floor is evaporated to no ethanol and distinguishes the flavor of;
(4) resin absorption, eluting, concentrate: macroporous resin column on the solution of extract that will obtain through (3), wash with water earlier and remove polysaccharide, protein etc., use 20%～80% ethanol elution then, collect eluent, after concentrated, drying, obtain Radix Morindae Officinalis platymiscium total glycosides extractive product.
6. extraction preparation method as claimed in claim 5 is characterized in that: said low polar organic solvent can be a petroleum ether, 6
#At least a in solvent for extraction, hexane, heptane, chloroform, ethyl acetate, the acetone.
7. the application of each described Radix Morindae Officinalis platymiscium total glycosides extractive of claim 1～5 in the medicine of preparation treatment snoring (also claiming sleep apnea syndrome (SAS)).
8. application as claimed in claim 7 is characterized in that: described sleep apnea syndrome (SAS) or snoring comprise central respiratory arrest syndrome (CSAS), obstructive apnea syndrome (OSAS) and MA syndrome.
9. pharmaceutical composition is characterized in that: it is that Radix Morindae Officinalis platymiscium total glycosides extractive with effective dose is an active component, adds the medicament that acceptable accessories or complementary composition are prepared from.
10. pharmaceutical composition according to claim 9 is characterized in that: described medicament comprises oral formulations or injection preparation.
11. a health-care food composition is characterized in that: it is that Radix Morindae Officinalis platymiscium total glycosides extractive with effective dose is an active component, adds the health food oral formulations that acceptable accessories or complementary composition are prepared from.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102191131A (en) * | 2011-03-08 | 2011-09-21 | 浙江农林大学 | Systemic preparation method of chrysanthemum rice essential oil, chrysanthemum rice polysaccharide, chrysanthemum total flavone extract and chrysanthemum rice powder |
| CN104374855A (en) * | 2014-08-21 | 2015-02-25 | 中国食品发酵工业研究院 | Method for simultaneous determination of asperuloside acid and deacetylasperulosidicacid content in Noni juice by HPLC |
| CN107056851A (en) * | 2017-06-05 | 2017-08-18 | 广东省微生物研究所（广东省微生物分析检测中心） | A kind of preparation method of the total oligosaccharide of Morinda officinalis |
| CN108542949A (en) * | 2018-05-08 | 2018-09-18 | 广西大学 | A kind of ultrasound assisted extraction Morinda officinalis anthraquinone analog compound method |
| WO2019219032A1 (en) * | 2018-05-17 | 2019-11-21 | 广州中医药大学 | Vitamin d receptor stimulant |
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2009
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102191131A (en) * | 2011-03-08 | 2011-09-21 | 浙江农林大学 | Systemic preparation method of chrysanthemum rice essential oil, chrysanthemum rice polysaccharide, chrysanthemum total flavone extract and chrysanthemum rice powder |
| CN104374855A (en) * | 2014-08-21 | 2015-02-25 | 中国食品发酵工业研究院 | Method for simultaneous determination of asperuloside acid and deacetylasperulosidicacid content in Noni juice by HPLC |
| CN104374855B (en) * | 2014-08-21 | 2016-03-09 | 中国食品发酵工业研究院 | The method of woodruff thuja acid and 10-deacetyl asperulosidic thuja acid content in HPLC Simultaneously test Noni juice |
| CN107056851A (en) * | 2017-06-05 | 2017-08-18 | 广东省微生物研究所（广东省微生物分析检测中心） | A kind of preparation method of the total oligosaccharide of Morinda officinalis |
| CN108542949A (en) * | 2018-05-08 | 2018-09-18 | 广西大学 | A kind of ultrasound assisted extraction Morinda officinalis anthraquinone analog compound method |
| WO2019219032A1 (en) * | 2018-05-17 | 2019-11-21 | 广州中医药大学 | Vitamin d receptor stimulant |
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