CN1813704A - Magnesium chlorogenate medicinal composition, its preparing method and use - Google Patents
Magnesium chlorogenate medicinal composition, its preparing method and use Download PDFInfo
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Abstract
The present invention relates to a magnesium chlorogenate medicine composition. It contains magnesium chlorogenate, magnesium isochlorogenate and chlorogenic acid, in which the content of magnesium chlorogenate is above 90%. Said medicine composition can be used for curing angiocardiopathy and cerebrovascular disease. Besides, said invention also provides its preparation method.
Description
Technical field:
The present invention relates to a kind of magnesium chlorogenate medicinal composition and its production and use.
Background technology:
Chlorogenic acid is the effective ingredient of Chinese medicine Flos Lonicerae, and content is higher, and the preparation of Flos Lonicerae is mainly used in anti-inflammation clinically.Generally be used for compound preparation, what folk prescription used mainly is oral, and its drug effect onset is slow, and bioavailability is low, and preparation technology is also complicated.By further developing new formulation in the classical medical material Flos Lonicerae, explore the medical usage that obtains new formulation by Flos Lonicerae, have great significance for comprehensive Chinese medicine treasure-house and the development of new medicine of effectively using.
Summary of the invention
The purpose of this invention is to provide a kind of magnesium chlorogenate compositions, another object of the present invention provides magnesium chlorogenate preparation of compositions method and purposes.
The invention provides a kind of magnesium chlorogenate medicinal composition, include magnesium chlorogenate, isochlorogenic acid magnesium, chlorogenic acid, wherein the content of magnesium chlorogenate is more than 90%.
Chlorogenic acid content is preferred more than 95%.
Magnesium chlorogenate medicinal composition of the present invention is realized by following steps:
1) Flos Lonicerae breaks into coarse powder, and 8-12 doubly measures deionized water extraction 2 times, and extracting solution is concentrated into 3g crude drug/ml after merging filtration, add 95% medicinal alcohol and regulate concentration of alcohol to 75-80%, the ammonia of adding 20% is regulated pH value to 8, fully stirs, and puts and leaves standstill 24h in the freezer;
2) get supernatant and reclaim ethanol, and continue to be evaporated to 4g crude drug/ml, fully stir 5 times of amounts of adding deionized waters down, add 20% ammonia and regulate pH value, put standing over night in the freezer to 9-10;
3) cold preservation liquid is centrifugal, the macroporous adsorbent resin that pretreatment is good on the solution (macroporous adsorbent resin can be AB-8, D101, HPD300 or ADS-8 resin), deionized water eluting with 1 times of amount bed volume, merge effluent and eluent, add 20% hydrochloric acid and regulate pH value to 1-2, use the ethyl acetate counter-current extraction, get extract;
4) extract reclaims ethyl acetate and remains half volume, add isopyknic deionized water, constantly add in the well-beaten process magnesium hydroxide solution to pH value to 10-12, isolate water, the extraction of reuse magnesium hydroxide water liquid once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.
The present invention also provides a kind of preparation of magnesium chlorogenate medicinal composition, forms by the pharmaceutically acceptable pharmaceutic adjuvant of magnesium chlorogenate compositions and corresponding dosage form, and can be injection, lyophilized powder, tablet, capsule or soft capsule.Preferred injection or lyophilized powder.
We have verified the application of magnesium chlorogenate medicinal composition aspect the preparation antiviral drugs by experiment.
We have also verified the application of magnesium chlorogenate medicinal composition aspect preparation treatment cardiovascular and cerebrovascular diseases medicament by experiment.
We successfully develop the magnesium chlorogenate compositions by the present invention, and have found the preparation method of said composition, and resultant composition technology favorable reproducibility is quality controllable, safety and stability.Pharmacological evaluation proof magnesium chlorogenate compositions has better antibacterial and anti-inflammation functions, and for cardiovascular and cerebrovascular disease therapeutical effect is arranged, and especially can be used for the protection of cardiovascular and cerebrovascular vessel ischemic damage and reperfusion damage.
Specific embodiment:
Embodiment 1: the preparation of magnesium chlorogenate medicinal composition
Get the 6kg Flos Lonicerae and break into coarse powder, add the 54L deionized water and be heated to 80 ℃, warm macerating extracts 2h, stirs once every 15 minutes, emits time extracting solution of winning; Medicinal residues add the 54L deionized water again and are heated to 80 ℃, and warm macerating extracts 2h, stir once every half an hour, get extracting solution for the second time.Merge extracted twice liquid and be concentrated into 3g crude drug/ml (2000ml), add 95% medicinal alcohol and regulate concentration of alcohol to 80%, add 20% ammonia adjusting pH value to 8, fully stir, put and leave standstill 24h in the freezer.Cold preservation liquid filters, and subsequent filtrate reclaims ethanol, and continues to be evaporated to 4g crude drug/ml (1500ml), fully stirs down to add the 7500ml deionized water, adds 20% ammonia and regulates pH value to 9-10 (measured value 9.9), puts standing over night in the freezer.Cold preservation liquid is centrifugal, the macroporous adsorbent resin that pretreatment is good on the solution (AB-8 resin, Nankai Univ. chemical plant, bed volume BV=5000ml), with the deionized water eluting of 1 times of amount bed volume (5000ml), merge effluent and eluent, add 20% hydrochloric acid and regulate pH value to 1-2 (measured value 1.2), use the ethyl acetate counter-current extraction, get extract 2000ml.Extract reclaims ethyl acetate to 1000ml, the deionized water that adds 1000ml, constantly add the magnesium hydroxide saturated solution in the well-beaten process to pH value to 10-12 (measured value 10.8), standing demix, isolate water, repeat above-mentioned magnesium hydroxide extracting operation once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.Sample number into spectrum: lysm-1.
Embodiment 2: the magnesium chlorogenate preparation of compositions
Get the 6kg Flos Lonicerae and break into coarse powder, add the 60L deionized water and be heated to 80 ℃, warm macerating extracts 2h, stirs once every 15 minutes, emits time extracting solution of winning; Medicinal residues add the 60L deionized water again and are heated to 80 ℃, and warm macerating extracts 2h, stir once every half an hour, get extracting solution for the second time.Merge extracted twice liquid and be concentrated into 3g crude drug/ml (2000ml), add 95% medicinal alcohol and regulate concentration of alcohol to 80%, add 20% ammonia adjusting pH value to 8, fully stir, put and leave standstill 24h in the freezer.Cold preservation liquid filters, and subsequent filtrate reclaims ethanol, and continues to be evaporated to 4g crude drug/ml (1500ml), fully stirs down to add the 7500ml deionized water, adds 20% ammonia and regulates pH value to 9-10 (measured value 9.2), puts standing over night in the freezer.Cold preservation liquid is centrifugal, the macroporous adsorbent resin that pretreatment is good on the solution (D101 resin, Tianjin insecticide factory produces, bed volume BV=5000ml), with the deionized water eluting of 1 times of amount bed volume (5000ml), merge effluent and eluent, add 20% hydrochloric acid and regulate pH value to 1-2 (measured value 1.5), use the ethyl acetate counter-current extraction, get extract 2000ml.Extract reclaims ethyl acetate to 1000ml, the deionized water that adds 1000ml, constantly add the magnesium hydroxide saturated solution in the well-beaten process to pH value to 10-12 (measured value 11.2), standing demix, isolate water, repeat above-mentioned magnesium hydroxide extracting operation once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.Sample number into spectrum: lysm-2.
Embodiment 3: the preparation of magnesium chlorogenate medicinal composition
Get the 6kg Flos Lonicerae and break into coarse powder, add the 66L deionized water and be heated to 80 ℃, warm macerating extracts 2h, stirs once every 15 minutes, emits time extracting solution of winning; Medicinal residues add the 66L deionized water again and are heated to 80 ℃, and warm macerating extracts 2h, stir once every half an hour, get extracting solution for the second time.Merge extracted twice liquid and be concentrated into 3g crude drug/ml (2000ml), add 95% medicinal alcohol and regulate concentration of alcohol to 80%, add 20% ammonia adjusting pH value to 8, fully stir, put and leave standstill 24h in the freezer.Cold preservation liquid filters, and subsequent filtrate reclaims ethanol, and continues to be evaporated to 4g crude drug/ml (1500ml), fully stirs down to add the 7500ml deionized water, adds 20% ammonia and regulates pH value to 9-10 (measured value 9.5), puts standing over night in the freezer.Cold preservation liquid is centrifugal, the macroporous adsorbent resin that pretreatment is good on the solution (HPD-300 resin, precious grace chemical plant, Cangzhou, bed volume BV=5000ml), with the deionized water eluting of 1 times of amount bed volume (5000ml), merge effluent and eluent, add 20% hydrochloric acid and regulate pH value to 1-2 (measured value 1.9, use the ethyl acetate counter-current extraction, get extract 2000ml.Extract reclaims ethyl acetate to 1000ml, the deionized water that adds 1000ml, constantly add the magnesium hydroxide saturated solution in the well-beaten process to pH value to 10-12 (measured value 11.8), standing demix, isolate water, repeat above-mentioned magnesium hydroxide extracting operation once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.Sample number into spectrum: lysm-3.
Embodiment 4: the preparation of chlorogenic acid for injection magnesium lyophilized powder
Get lysm-1 sample 20g, fully be dissolved in the 500ml water for injection, cold preservation was filtered in 24 hours, filtrate adds 30g mannitol, cross 0.45 micron microporous filter membrane, add the injection water and be settled to 600ml, filter, fine straining, be sub-packed in every 3ml in the 7ml cillin bottle, jump a queue lyophilizing, gland adds aluminium lid and promptly gets chlorogenic acid for injection magnesium lyophilized powder.Lot number: lyophilized powder lysmdg-1
Embodiment 5: the preparation of chlorogenic acid for injection magnesium lyophilized powder
Get lysm-2 sample 10g, fully be dissolved in the 500ml water for injection, cold preservation was filtered in 24 hours, filtrate adds 36g mannitol, cross 0.45 micron microporous filter membrane, add the injection water and be settled to 600ml, filter, fine straining, be sub-packed in every 3ml in the 7ml cillin bottle, jump a queue lyophilizing, gland adds aluminium lid and promptly gets chlorogenic acid for injection magnesium lyophilized powder.Lot number: lyophilized powder lysmdg-2
Embodiment 6: the preparation of chlorogenic acid for injection magnesium lyophilized powder
Get lysm-1 sample 6g, fully be dissolved in the 500ml water for injection, cold preservation was filtered in 24 hours, filtrate adds 48g mannitol, cross 0.45 micron microporous filter membrane, add the injection water and be settled to 600ml, filter, fine straining, be sub-packed in every 3ml in the 7ml cillin bottle, jump a queue lyophilizing, gland adds aluminium lid and promptly gets chlorogenic acid for injection magnesium lyophilized powder.Lot number: lyophilized powder lysmdg-3
Embodiment 7: the preparation of chlorogenic acid for injection magnesium lyophilized powder
Get lysm-3 sample 20g, fully be dissolved in the 500ml water for injection, cold preservation was filtered in 24 hours, filtrate adds 48g mannitol, cross 0.45 micron microporous filter membrane, add the injection water and be settled to 600ml, filter, fine straining, be sub-packed in every 3ml in the 7ml cillin bottle, jump a queue lyophilizing, gland adds aluminium lid and promptly gets chlorogenic acid for injection magnesium lyophilized powder.Lot number: lyophilized powder lysmdg-4
Embodiment 8: the protective effect research of magnesium chlorogenate salt pair cerebral ischemia
Experiment medicine: injection of the present invention
The pentoxifylline injection
Normal saline
Laboratory animal: 100 of Wistar II level rat, male and female half and half, body weight 200g-250g
Test method:
Make focal cerebral ischemia in rats-reperfusion injury model with line bolt legal system.The nylon wire of choosing is cut into 5cm length, and an end is slowly heating on alcohol burner, makes its head end become little and slick spheroid, marks apart from pommel 20mm place, and the sterilization postposition is placed in the isotonic saline solution standby.With 20% urethane (750mg/kg) intraperitoneal injection of anesthesia rat, the side position is fixed on the operating-table, vertically cuts the about 2.5cm of skin and successively separate before the left neck ear, free left common carotid artery, internal carotid artery.Heat is cut off external carotid artery proximal part branch with fixed attention, and ligation external carotid artery far-end coagulates cut-out in ligation place far-end heat, separates internal carotid artery to the basis cranii direction then, and careful arteria pterygopalatina and its root of ligation of separating only keeps internal carotid artery and go into the basis cranii trunk.Close internal carotid artery and common carotid artery with the temporary transient folder of small-sized bulldog clamp, tractive external carotid artery stump, consistent with the internal carotid artery direction.Under the external carotid artery stump, be equipped with line, cut an osculum with eye scissors at the external carotid artery stump then the common carotid artery crotch is slowly inserted in the nylon wire pommel, enter internal carotid artery then.When nylon wire entered the about 17.5-18.5mm of internal carotid artery resistance sense is arranged, nylon wire was crooked gently, shows that its head end by the section start of middle cerebral artery, enters anterior cerebral artery, had blocked the blood flow of middle cerebral artery this moment.Stump at external carotid artery is equipped with the line place, and ligation is nylon wire fixedly, sews up isolating muscle, skin, and the tail end of nylon wire is placed outside the skin.When pouring into, draw nylon wire outward again, its head end is back in the external carotid artery, can recover blood supply, and the nylon wire of outside is cut off, reach postoperative in the art and note keeping rat temperature, room temperature remains on 20-24 ℃.
The experiment grouping:
(1) biochemistry detection group: 50 rats branches are divided into 5 groups every group 10 at random.1. sham operated rats: only cut skin, separate tremulous pulse, do not block middle cerebral artery, lumbar injection isotonic saline solution 2ml.2. model group: block middle cerebral artery, immediately behind the lumbar injection isotonic saline solution 2ml, be made into ischemia 2h, pour into the 3h rat model again.3. low dose group: block middle cerebral artery, lumbar injection chlorogenic acid magnesium salt (10mg/kg+2ml isotonic saline solution) immediately is made into ischemia 2h, pours into the 3h rat model again.4. high dose group: block middle cerebral artery, lumbar injection chlorogenic acid magnesium salt (30mg/kg+2ml isotonic saline solution) is immediately made ischemia 2h, is poured into the 3h rat model again.5. magnesium chlorogenate matched group: block middle cerebral artery, lumbar injection pentoxifylline (30mg/kg+2ml isotonic saline solution) is immediately made ischemia 2h, is poured into the 3h rat model again.
(2) behavioristics, pathology test set: 50 rats are divided into 5 groups every group 10 at random.1. sham operated rats: only cut skin, separate tremulous pulse, do not block middle cerebral artery, lumbar injection isotonic saline solution 2ml.2. model group: block middle cerebral artery, immediately behind the lumbar injection isotonic saline solution 2ml, be made into ischemia 3h, pour into the 24h rat model again.3. low dose group: block middle cerebral artery, lumbar injection chlorogenic acid magnesium salt (10mg/kg+2ml isotonic saline solution) immediately is made into ischemia 3h, pours into the 2h rat model again.4. high dose group: block middle cerebral artery, lumbar injection chlorogenic acid magnesium salt (30mg/kg+2ml isotonic saline solution) is immediately made ischemia 3h, is poured into the 24h rat model again.5. chlorogenic acid matched group: block middle cerebral artery, lumbar injection chlorogenic acid (30mg/kg+2ml isotonic saline solution) is immediately made ischemia 3h, is poured into the 24h rat model again.
Detect index and method:
(1) rat of 50 modeling successes in the biochemistry detection group is put to death in the detection of NO, NOS, SOD, MDA content in the cerebral tissue, gets brain on ice pan rapidly, and the left side brain is made 10% brain tissue homogenate, and the centrifugal 10min of 4000r/min gets supernatant.The NOS activity is measured in explanation according to test kit, uses nitrate reductase method and measures NO content.Use xanthine oxidase and measure the SOD activity.Using modified Yagi spark gap state husband method is measured MDA content.The results are shown in Table 1.
(2) neuroethology change to be observed: after behavioristics, the success of pathology test set rat modeling, by the observer who does not understand the grouping situation, press 5 grades of point systems of Longa etc., the evaluate recorded neuroethology is marked.0 grade: the impassivity functional impairment, the limbs words are moving normal; 1 grade: slight focal lesion, can not secondaryly open up left fore; 2 grades: the moderate focal lesion, draw circle to the left; 3 grades: the severe focal lesion, topple over to the left; 4 grades: utmost point severe focal lesion does not have autonomous walking and disturbance of consciousness.Behind the rat deep anaesthesia, in ice pan, get cerebral tissue rapidly, with the crown incision of brain, the 2mm place makes coronal section before distance optic chiasma recess from the optic chiasma recess, and the left side brain tissue slice of thick about 2mm is placed 2%TTC solution, hatch 30min for 37 ℃, infarcted region presents white, and non-infarcted region presents redness, and digital camera is taken record, measure full brain sheet cumulative volume and infarct volume, and calculate the percentage ratio that infarct accounts for the brain cumulative volume.The results are shown in Table 2,3.
Table 1 chlorogenic acid is to the content influence of NO, NOS, MDA, SOD in the cerebral ischemia cerebral tissue
| Group | Example number (n) | NO (nmol/mg) | NOS (nmol/mg) | MDA (nmol/100mg) | SOD (NU/100mg) |
| Sham operated rats | 10 | 0.83±0.05 | 0.138±0.017 | 48.0±0.29 | 197±8 |
| Model group | 10 | 1.21±0.04 ** | 0.253±0.019 ** | 69.7±3.2 ** | 130±7 ** |
| Low dose group | 10 | 0.89±0.06 △△ | 0.169±0.012 △△ | 49.8±2.5 △△ | 190±7 △△ |
| High dose group | 10 | 0.75±0.04 △△ | 0.153±0.018 △△ | 44.3±2.0 △△ | 223±7 △△ |
| Chlorogenic acid | 10 | 0.88±0.04 △△ | 0.179±0.018 △△ | 45.3±2.0 △△ | 182±7 △△ |
Annotate: compare * P＜0.05 * * P＜0.01 with sham operated rats
Compare △ P＜0.05 △ △ P＜0.01 with model group
Table 2 chlorogenic acid pours into the influence of neurological's scoring of 24h again to rat cerebral ischemia 3h
| Group | Dosage (mg/kg) | Example number (n) | Behavior scoring |
| Sham operated rats | - | 10 | 0.0±0.00 |
| Model group | - | 10 | 1.8±0.79 |
| Low dose group | 10 | 10 | 0.8±0.64** |
| High dose group | 30 | 10 | 0.6±0.59** |
| Chlorogenic acid | 30 | 10 | 0.8±0.68** |
Compare * P＜0.05 * * P＜0.01 with model group
The influence of the cerebral infarct volume of table 3 pair cerebral ischemic reperfusion in rats
| Group | Dosage (mg/kg) | Example number (n) | Infarct volume percentage ratio (%) |
| Sham operated rats | - | 10 | 0.0 |
| Model group | - | 10 | 29.7±3.13 |
| Low dose group | 10 | 10 | 9.23±2.56** |
| High dose group | 30 | 10 | 5.92±2.68** |
| Chlorogenic acid | 30 | 10 | 8.92±2.68** |
Compare * P＜0.05 * * P＜0.01 with model group
Embodiment 9: chlorogenic acid is to the protective effect research of rat myocardial ischemia and reperfusion damage
Experiment medicine: injection of the present invention
SHENGMAI ZHUSHEYE
Normal saline
Laboratory animal: 50 of Wistar II level rat, male and female half and half, body weight 200g-250g
Experimental technique:
With coronary ligation manufactured rat myocardial ischemia and reperfusion damage model, rats by intraperitoneal injection 3% pentobarbital sodium anesthesia (30mg/kg), place on the rat operating-table fixedly dorsal position to fix, the longitudinal incision skin of neck, passivity is separated the trachea surrounding tissue, exposes trachea, circulation of qi promoting pipe interpolation pipe, and confirm to insert in the trachea, back suture fixedly intubate by the rat mouth.In rat oxter parallel lines, transection skin about 1.5cm in left side separates the flesh layer in the 4th or the 5th intercostal passivity, opens the thoracic cavity, is right after animal respirator, auxiliary rats breathing.Cut off pericardium, gently press the right side thorax, extrude heart, at pulmonary conus right border, flat left auricle lower edge 1-2mm place, superficial layer of myocardium is worn line No. 5/0 under left coronary artery, together with a diameter 2mm polrvinyl chloride tubal ligation left anterior descending coronary artery, causes myocardial ischemia.Behind the ligation arteria coronaria 1 hour, cut off polychlorostyrene second pipe with eye scissors and cut off silk thread simultaneously, make ischemic myocardium recover blood perfusion, pour into again and finish experiment after 3 hours.Lead the sign that the model success was raised or be reduced to the ST section with SUMP-PC type four roads biological signal acquisition process continuous record standard limbs II in the whole experiment.
The experiment grouping:
At random 50 rats are divided into 5 groups, 10 every group.1. sham operated rats: only cut the thoracic cavity, expose heart, threading but not ligation coronary artery, lumbar injection isotonic saline solution 2ml.2. model group: threading ligation coronary artery immediately behind the lumbar injection isotonic saline solution 2ml, is made into ischemia 1h, pours into the 3h rat model again.3. low dose group: threading ligation coronary artery immediately behind the lumbar injection chlorogenic acid (10mg/kg+2ml isotonic saline solution), is made into ischemia 1h, pours into the 3h rat model again.4. high dose group: threading ligation coronary artery immediately behind the lumbar injection chlorogenic acid (30mg/kg+2ml isotonic saline solution), is made into ischemia 1h, pours into the 3h rat model again.5. SHENGMAI ZHUSHEYE matched group: threading ligation coronary artery immediately after the lumbar injection SHENGMAI ZHUSHEYE (1ml/kg+2ml isotonic saline solution), is made into ischemia 1h, pours into the 3h rat model again.
Detect index:
(1) rat blood serum CPK, LDH, SOD, M DA determination of activity, at once treating the preponderant disease instead of the secondary disease blood 5ml separation of serum after perfusion finishes again, creatine phosphokinase (CPK) and lactic acid dehydrogenase (LDH) press test kit mensuration enzymatic activity, SOD are described, malonaldehyde (MDA) detects activity of SOD in serum and M DA content according to the test kit operation with UV-754 type ultraviolet-uisible spectrophotometer.The results are shown in Table 4.
(2) detection of NO, NOS, SOD, MDA content in the cardiac muscular tissue, after perfusion finishes again the rat of modeling success is put to death, the dirty tissue of coring rapidly, with the clean cardiac muscular tissue of ice normal saline flushing bloodstain, after making 10% myocardium homogenate under 4 ℃ of conditions, the centrifugal 10min of 4000r/min gets supernatant.Myocardium NO, NOS, SOD activity and MDA content are measured in explanation according to test kit.The results are shown in Table 5.
Table 4 chlorogenic acid is to CPK in the rat myocardial ischemia and reperfusion damage serum, LDH, SOD, the influence of MDA
| Group | Example number (n) | CPK (U/L) | LDH (U/L) | SOD (U/L) | MDA (umol/L) |
| Sham operated rats | 10 | 115.6±7.2 | 34.6±1.3 | 418±31 | 4.3±1.2 |
| Model group | 10 | 2015.8±125.3 ** | 391.5±24.6 ** | 309±22 ** | 13.5±2.6 ** |
| Low dose group | 10 | 475.5±28.9 **△△ | 129.4±14.2 **△△ | 382±24 △△ | 5.5±1.3 △△ |
| High dose group | 10 | 259.1±23.5 **△△ | 86.7±9.2 **△△ | 427±35 △△ | 4.0±1.4 △△ |
| Chlorogenic acid | 10 | 442.9±31.2 **△△ | 118.6±13.4 **△△ | 397±24 △△ | 5.0±2.3 △△ |
Annotate: compare * P＜0.05 * * P＜0.01 with sham operated rats
Compare △ P＜0.05 △ △ P＜0.01 with model group
Table 5 chlorogenic acid is organized NO to the rat myocardial ischemia and reperfusion injury of myocardium, NOS, SOD, the influence of MDA
| Group | The example number | NO (nmol/mg) | NOS (nmol/mg) | MDA (nmol/100mg) | SOD (NU/100mg) |
| Sham operated rats | 10 | 4.69±0.25 | 0.235±0.017 | 12.0±1.2 | 281±29 |
| Model group | 10 | 2.25±0.14 ** | 0.354±0.017 ** | 39.6±4.3 ** | 192±14 ** |
| Low dose group | 10 | 4.78±0.16 △△ | 0.252±0.015 △△ | 16.4±2.8 *△△ | 267±27 △△ |
| High dose group | 10 | 5.18±0.21 △△ | 0.205±0.014 △△ | 11.6±2.3 △△ | 329±34 △△ |
| Chlorogenic acid | 10 | 5.38±0.24 *△△ | 0.265±0.016 △△ | 15.3±3.2 △△ | 279±23 △△ |
Annotate: compare * P＜0.05 * * P＜0.01 with sham operated rats
Compare △ P＜0.05 △ △ P＜0.01 with model group
Claims (10)
1, a kind of magnesium chlorogenate medicinal composition includes magnesium chlorogenate, isochlorogenic acid magnesium, chlorogenic acid, and wherein the content of magnesium chlorogenate is more than 90%.
2, as claim 1 described magnesium chlorogenate medicinal composition, the content that it is characterized in that magnesium chlorogenate is more than 95%.
3, a kind of magnesium chlorogenate medicinal composition, realize by following steps:
1) Flos Lonicerae breaks into coarse powder, and 8-12 doubly measures deionized water extraction 2 times, and extracting solution is concentrated into 3g crude drug/ml after merging filtration, add 95% medicinal alcohol and regulate concentration of alcohol to 75-80%, the ammonia of adding 20% is regulated pH value to 8, fully stirs, and puts and leaves standstill 24h in the freezer;
2) get supernatant and reclaim ethanol, and continue to be evaporated to 4g crude drug/ml, fully stir 5 times of amounts of adding deionized waters down, add 20% ammonia and regulate pH value, put standing over night in the freezer to 9-10;
3) cold preservation liquid is centrifugal, the good macroporous adsorbent resin of pretreatment on the solution, and the deionized water eluting with 1 times of amount bed volume merges effluent and eluent, adds 20% hydrochloric acid and regulates pH value to 1-2, uses the ethyl acetate counter-current extraction, gets extract;
4) extract reclaims ethyl acetate and remains half volume, add isopyknic deionized water, constantly add in the well-beaten process magnesium hydroxide solution to pH value to 10-12, isolate water, the extraction of reuse magnesium hydroxide water liquid once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.
4, a kind of preparation method of magnesium chlorogenate medicinal composition is characterized in that finishing according to the following steps:
1) Flos Lonicerae breaks into coarse powder, and 8-12 doubly measures deionized water extraction 2 times, and extracting solution is concentrated into 3g crude drug/ml after merging filtration, add 95% medicinal alcohol and regulate concentration of alcohol to 75-80%, the ammonia of adding 20% is regulated pH value to 8, fully stirs, and puts and leaves standstill 24h in the freezer;
2) get supernatant and reclaim ethanol, and continue to be evaporated to 4g crude drug/ml, fully stir 5 times of amounts of adding deionized waters down, add 20% ammonia and regulate pH value, put standing over night in the freezer to 9-10;
3) cold preservation liquid is centrifugal, the good macroporous adsorbent resin of pretreatment on the solution, and the deionized water eluting with 1 times of amount bed volume merges effluent and eluent, adds 20% hydrochloric acid and regulates pH value to 1-2, uses the ethyl acetate counter-current extraction, gets extract;
4) extract reclaims ethyl acetate and remains half volume, add isopyknic deionized water, constantly add in the well-beaten process magnesium hydroxide solution to pH value to 10-12, isolate water, the extraction of reuse magnesium hydroxide water liquid once, merge twice extraction water liquid and be evaporated to the greatest extent, cold drying gets the magnesium chlorogenate compositions.
5,, it is characterized in that it is 80% that the first step is regulated concentration of alcohol as the preparation method of claim 4 described magnesium chlorogenate medicinal compositions.
6,, it is characterized in that described macroporous adsorbent resin of the 3rd step is AB-8, D101, HPD300 or ADS-8 resin as the preparation method of claim 4 described magnesium chlorogenate medicinal compositions.
7, a kind of preparation of magnesium chlorogenate medicinal composition is made up of the pharmaceutically acceptable pharmaceutic adjuvant of magnesium chlorogenate compositions and corresponding dosage form, can be injection, lyophilized powder, tablet, capsule or soft capsule.
8,, it is characterized in that dosage form is injection or injection lyophilized powder as the preparation of claim 6 described magnesium chlorogenate medicinal compositions.
9, as claim 3 described magnesium chlorogenate medicinal compositions in the application of preparation aspect the antiviral drugs.
10, as claim 3 described magnesium chlorogenate medicinal compositions in the application aspect the preparation treatment cardiovascular and cerebrovascular diseases medicament.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176879A (en) * | 2016-07-27 | 2016-12-07 | 南京正宽医药科技有限公司 | The process of preparing Chinese medicine extracting method of a kind of Flos Lonicerae decoction pieces and honeysuckle mouthwash |
| CN106728137A (en) * | 2016-11-24 | 2017-05-31 | 广州和匠科技有限公司 | It is a kind of that the preparation method for preventing and treating hyperuricemia and gout medicine-food two-purpose monomer is extracted from coffee |
| CN112402477A (en) * | 2019-08-23 | 2021-02-26 | 河南诺美药业有限公司 | Process for hot-pressing countercurrent extraction of honeysuckle |
| CN112778134A (en) * | 2019-11-08 | 2021-05-11 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
-
2005
- 2005-11-23 CN CN 200510101424 patent/CN1813704A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176879A (en) * | 2016-07-27 | 2016-12-07 | 南京正宽医药科技有限公司 | The process of preparing Chinese medicine extracting method of a kind of Flos Lonicerae decoction pieces and honeysuckle mouthwash |
| CN106728137A (en) * | 2016-11-24 | 2017-05-31 | 广州和匠科技有限公司 | It is a kind of that the preparation method for preventing and treating hyperuricemia and gout medicine-food two-purpose monomer is extracted from coffee |
| CN112402477A (en) * | 2019-08-23 | 2021-02-26 | 河南诺美药业有限公司 | Process for hot-pressing countercurrent extraction of honeysuckle |
| CN112778134A (en) * | 2019-11-08 | 2021-05-11 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
| CN112778134B (en) * | 2019-11-08 | 2022-10-28 | 北京科莱博医药开发有限责任公司 | Chlorogenic acid calcium salt sesquihydrate and application thereof |
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