CN102670592B - Motherwort alkaloid and choline medicinal composition - Google Patents
Motherwort alkaloid and choline medicinal composition Download PDFInfo
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Abstract
The invention discloses a motherwort alkaloid and choline medicinal composition, in particular a stachydrine and/or motherwort alkaloid and choline medicinal composition, a preparation method of the composition and application of the composition.
Description
Technical field
The invention belongs to field of medicinal compositions, particularly the compositions of a kind of Herba Leonuri alkaloid and choline or its pharmaceutical salts, its preparation method, and uses thereof.
Background technology
At present, postpartum hemorrhage is still and causes the topmost reason of China's maternal death.Postpartum hemorrhage delivering by vagina incidence rate accounts for 3%～5% of childbirth sum.The main cause that causes postpartum hemorrhage has that uterine contraction is weak, Placenta Hominis factor, soft birth canal injury and coagulation disorders.Wherein, uterine contraction is weak is to cause hemorrhage modal reason.
Force of labor comprises strength of uterine contraction, stomach wall flesh and contraction of diaphragm power and contractive ability of musculus levator ani, wherein taking strength of uterine contraction as main.In birth process, the undesired or intensity of uterotonic rhythmicity, symmetry and polarity, frequency change, and are called abnormality of uterine contraction.How because of birth canal or the obstructive difficult labour of fetal factors abnormal formation, make fetus pass through birth canal resistance increment clinically, cause Secondary cases abnormal uterine action.Abnormality of uterine contraction is divided into weak and metrypercinesia two classes of uterine contraction clinically, and every class is sent out again as harmony uterine contraction and incoordination uterine contraction.
How uterine contraction is weak is caused by several combined factors, common reason has: 1. cephalopelvic disproportion or abnormal fetal position fetus presentation subordinate fall and be obstructed, can not be close to lower uterine segment and cervix uteri, thereby can not cause reflexive uterine contraction, cause Secondary cases uterine contraction weak.2. uterine factors uterine hypoplasia, uterine malformation (as uterus bicornis etc.), Uterus wall excessive expansion (as twins, fetal macrosomia, polyhydramnios etc.), multipara (multipara) uterus muscle fibre modification or hysteromyoma etc., all can cause that uterine contraction is weak.3. Nervous and Mental Factors primipara (primipara) [especially more than 35 years old elderly primipara (elderly primipara)], spirit hypertonicity makes cerebral cortex dysfunction, sleep is few, just before giving birth laggard lack of appetite and consuming one's strength too much, all can cause uterine contraction weak.Endocrine disturbance just before giving birth after, the hyposecretions such as puerpera's body inner estrogen, oxytocin, prostaglandin, acetylcholine, progestogen decline slowly, the Reduced susceptibilities of uterus to acetylcholine etc., all can affect uterus muscle threshold of excitation, cause uterine contraction weak.5. drug influence uses heavy dose of tranquilizer and analgesics after just before giving birth inadequately, as morphine, chlorpromazine, pethidine, barbital etc., can make uterine contraction be suppressed.
In recent years, along with obstetrics of China treatment level improves constantly, anaesthesia technology constantly improves, cuing open palace produces and becomes gradually the primary treatment measure that solves difficult labour and obstetric complication, complication, but how to reduce in cesarean section, postoperative amount of bleeding, be still one of subject matter of puzzlement China obstetrist.What the palace of contracting at present medicine was the most frequently used is oxytocin.It is cheap, easy to use, but has larger individual variation, and prostaglandins contracting palace drug price is more expensive, allergy is heavier.Herba Leonuri treatment postpartum hemorrhage, in the history of the existing more than one thousand years of China, its oral medication postpartum hemorrhage is effective, and safe and reliable.
Herba Leonuri is the young stem and leaf of labiate Herba Leonuri (Leonurus heterophyllus Sweet).Herba Leonuri young stem and leaf contains the multiple nutritional components such as protein, carbohydrate, and nature and flavor are arduous cool, have invigorate blood circulation, effect of blood stasis dispelling, regulating menstruation, the water that disappears, control water, hematuria under menoxenia, edema, rush down blood, dysentery, haemorrhoids.
In Herba Leonuri, contain leonurine (Leonurine), stachydrine (Stachydrine), leonuridine (Leonuridine), leonurinine (Leonurinine), linolenic acid (Linolenic acid), β-linolenic acid, lauric acid (Lauric acid), oleic acid, benzoic acid, globulariacitrin (Rutin), Fumaric acid (Fumaric acid), sterol, vitamin A etc.In addition also containing arginine, 4-guanidine radicals-n-butyl alcohol (4-Guanidino-1-butanol), 4-guanidine radicals butanoic acid (4-Guanidino-butyric acid), stachyose (Stachyose).Still extract to obtain five kinds of crystalline materials, two kinds for alkaloid be leonurine first, second; Three kinds is non-alkaloid, i.e. Herba Leonuri element first, second, third.
Herba Leonuri has excitation to uterus.Herba Leonuri decoct, water logging or ethanol extract and Herba Leonuri total alkali all have excitation to the uterus of the many animals such as Cavia porcellus, rabbit, cat, dog.Experiment showed, that Herba Leonuri decoct, to unpregnancy, early pregnancy, late pregnancy or isolated rabbit in puerperal uterus, all has excitation.In uterus in place, there is excitation in rapid intravenous injection, its intensity and action time strengthen and increase with consumption after half a minute.The test of rabbit uterus fistula, by Herba Leonuri decoct gavage, in the time that intrauterine pressurizes or do not pressurize, all after 15～20 minutes, makes uterus be significant excitation in administration.Herba Leonuri total alkali has excitation to guinea pig in vitro uterus, and it acts on similar ergometrine.Herba Leonuri total alkaloids 3mg and Cornocentin 0.04mg tire quite.Herba Leonuri water logging or ethanol extract all have remarkable excitation to uterus in vitro and in place.But to uterus in place, first have the inhibitory action of a short time before excitement, the aqueous solution after ether extraction, without this inhibitory action.Therefore, in Herba Leonuri, may contain two kinds of compositions of inhibition and irritability.Leonurine can make the Isolated Rat Uterus amplitude of intramuscular injection estradiol 50mg after proestrus or oophorectomize increase, and its effect is relevant to dosage, shows as dosage-tension force linear.Leonurine sustainable several hours to the contraction in uterus, but can recover after rinsing.Atropine 2mg/ml does not affect its contraction.Leonurine first 2.5～5mg/kg, to anesthetized cat intravenous injection, has excitation to uterus, can increase uterus tension force, and energy blood pressure lowering; Also there is to excitation in cat, guinea pig in vitro uterus.The but ametria contraction of Herba Leonuri injection making through the way of distillation.Herba Leonuri water decoction, to oral 4～5 times of mice (total amount 200～250mg), has certain anti-implantation and antiearly pregnancy effect. and have report to point out, the effective ingredient in the excited uterus of Herba Leonuri is mainly present in leaf portion, and root effect is very weak, and base portion is invalid.
Choline English name is Choline, and molecular formula is C
5h
15nO
2, molecular weight is 121.18, is a kind of strong organic base, is the constituent of lecithin, is also present among sphingomyelin, is that of the variable methyl of body originates and acts on the product of synthesizing methyl, is again the precursor of acetylcholine simultaneously.Choline is heat-resisting, and the loss in processing and gastronomical process is little, under dry environment, does not also almost change even if store for a long time content of choline in food.Choline is the important component part of the sphingomyelins of lecithin, and lecithin be phosphatidylcholine, is extensively present in animals and plants.Choline is the water solublity white serosity of colourless bitter in the mouth, has very strong hygroscopicity, is exposed in air and can absorbs water very soon.The crystal salt (as choline chloride) that choline is easy and acid reaction generation is more stable, also unstable under highly basic condition, but to heat and storage quite stable.Because choline is heat-resisting, therefore the loss in processing and gastronomical process is little, does not also almost change even if store for a long time content of choline in food under dry environment.
Choline is the important component part of lecithin and sphingomyelins, lecithin be phosphatidylcholine (phosphalidy chlines), extensively be formed in the bodies of aminal and plant, in brain, seminal fluid, adrenal gland and the cell of animal, content is especially many, the abundantest with the content in fowl ovum yolk, reach 8%～10% of dry weight.Sphingomyelins (sphingomyelin) is the Typical Representative of neural alcohol phospholipid, and in higher mammal tissue, content is the abundantest, and it is made up of sphingosine, fatty acid, phospholipid and choline.
Summary of the invention
One of object of the present invention is to provide a kind of new pharmaceutical composition, and pharmaceutical composition of the present invention contains Herba Leonuri alkaloid and choline.Herba Leonuri alkaloid in the present invention is selected from one or more in stachydrine, leonurine, leonuridine, leonurinine, leonurine first, leonurine second, can also be Herba Leonuri extract, Herba Leonuri extract includes but not limited to motherwort aqueous extract and Herba Leonuri ethanol extract.The preferred stachydrine of Herba Leonuri alkaloid, leonurine or leonurinine, more preferably stachydrine in the present invention.
Choline in the present invention can be the form of free alkali, can be also the form of its pharmaceutical salts, and choline pharmaceutical salts includes but not limited to choline chloride, succinic acid choline.Choline in the present invention is preferably the form of free alkali.
In pharmaceutical composition of the present invention, the weight ratio of Herba Leonuri alkaloid and choline is 100: 1-1: 100, and preferably the weight ratio of Herba Leonuri alkaloid and choline is 10: 1-1: 10.
Research worker of the present invention is surprised to find choline can obviously strengthen the hemorrhage effect of Herba Leonuri alkaloid inhibition rat uterus.
Compositions of the present invention is by Herba Leonuri alkaloid and choline are directly mixed, or is mixed with suitable solvent or pharmaceutic adjuvant.
Stachydrine in the present invention can extract according to the method for bibliographical information preparation by chemosynthesis or from plant.For example, He Liqin etc. have reported the synthetic method (stachydrine synthesising process research, West China pharmaceutical journal, 2005,20 (1): 50-51) of stachydrine.
Leonurine in the present invention can be according to the method preparation providing in patent application (application publication number CN1415602).
Pharmaceutical composition of the present invention is by adding suitable pharmaceutic adjuvant, can make different pharmaceutical preparation, the pharmaceutical preparation that pharmaceutical composition of the present invention can be made includes but not limited to injection, injectable powder, tablet, capsule, soft capsule, pill, drop pill, granule, oral liquid, syrup, powder, unguentum, oil preparation, suppository, liniment, gel.
For example, the tablet that pharmaceutical composition of the present invention is made can add binding agent, disintegrating agent, filler, wetting agent, lubricant etc. as required.Wherein filler is selected from starch, Icing Sugar, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, inorganic salts, mannitol etc.Wherein wetting agent and binding agent are selected from distilled water, ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methylcellulose and ethyl cellulose, hydroxypropyl emthylcellulose, polyvinylpyrrolidone, gelatin solution, sucrose solution etc.Wherein disintegrating agent is selected from dried starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose etc.Wherein lubricant is selected from magnesium stearate, silica gel, Pulvis Talci, hydrogenated vegetable oil, Polyethylene Glycol etc.
In the specific embodiment of the present invention, choline and stachydrine show synergism in to pregnant guinea pig in vitro uterine myometrium Experiment on Function.
Adopt rat commotio retinae metrorrhagia model to investigate pharmaceutical composition of the present invention to the hemorrhage impact of rat uterus, find that cholinergic obviously strengthens the alkaloidal anastalsis of Herba Leonuri, choline and Herba Leonuri alkaloid have synergism.
The pharmaceutical preparation that pharmaceutical composition of the present invention is made can be used for the treatment of dysfunctional uterine hemorrhage; Vaginal hemorrhage after artificial abortion, medicine stream (induction of labour in second trimester), spontaneous abortion; Climacteric syndrome; Puerperal cyasma, menoxenia, menorrhagia, amenorrhea, dysmenorrhea (abdominal pain in menstruation, lower abdominal distention pain, pain in the low back and legs etc.); Metrorrhagia (many and more than the collapsing of calling of the menses amount of breaking with tremendous force; The leakage of menses dripping urine endlessly meaning); Prolonged lochia, placental retention etc.
The pharmaceutical preparation of pharmaceutical composition of the present invention also can be clinical in improving blood supply of cardiac muscle allevating angina pectoris, reducing blood viscosity, blood fat reducing etc.
Pharmaceutical composition of the present invention also can be applied preparing in cosmetics, article of everyday use.
Detailed description of the invention
Following examples, for further explaination the present invention, are not construed as limiting the invention.
Embodiment 1 is to the effect of pregnant guinea pig in vitro uterine myometrium
Britain plants in pregnant Cavia porcellus 24h in puerperal, tests.In experiment the same day with ironware fiercely attack head put to death Cavia porcellus, facing upward position is fixed in surgical tray, middle hypogastric region is made one " V " word otch, find out uterus, separate surrounding tissue, get fallopian tube to the about 1.5-2cm in uterus, stage casing between the crotch of uterus, wipe out surrounding tissue, cut cornua uteri open along the mesentery longitudinal axis, in tyrode's solution, rinsing is clean.Be laid in the culture dish that contains tyrode's solution (37 DEG C ± 0.5 DEG C of temperature), with the fixing uterus of ophthalmic tweezers bar, got the wide longitudinal muscle bar for 5mm along smooth muscle fiber direction, for subsequent use.
By flesh bar knotting, after other end knotting, tie again the ring of a diameter 0.5cm with stitching thread, and by articulating to sensor.Insert 60ml Tai Shi and bathe in ware, put into constant temperature water bath.Tonotransducer is connected with the input interface CH-1 of BL-410 system.Assumed load is adjusted to 1 ± 0.1g, and water temperature is constant in 37 DEG C ± 0.5 DEG C, for O
260 bubble/min.Test sample and the positive reference substance of variable concentrations reinject after the spontaneous activity of flesh bar steadily.
Debugging BL-410 system, selects 1 passage, and relevant parameter (G100, TDC, F30HZ), scanning speed 64S/div are set.
Due to the intrapartum uncertainty of pregnant Cavia porcellus, therefore by the sequencing of pregnant Mus childbirth by 28 puerperal Cavia porcellus be divided in turn positive controls (1 group), stachydrine+choline group (2 groups), choline group (3 groups), stachydrine group (4 groups).
Detected parameters is selected as follows:
Frequency (inferior/min)--number of contractions per minute
Tension force (mg)--each minimum point of shrinking
Intensity (mg)--each peak shrinking
Uterine contraction amplitude (mg)=intensity-tension force
Frequency before frequency-administration after Δ frequency (inferior/min)=administration
Δ tension force (mg)=administration backward pull-administration forward pull
Intensity before intensity-administration after Δ intensity (mg)=administration
Uterine contraction amplitude before uterine contraction amplitude-administration after Δ uterine contraction amplitude (mg)=administration
Positive controls: inject 60ml tyrode's solution (37 DEG C ± 0.5 DEG C) to holding in ware, observed and recorded is the tension force 20-25min of flesh bar contraction frequency, contraction wave mean amplitude of tide, contraction wave interval average duration and smooth muscle under normal circumstances.Hold in ware and inject 10 μ/ml oxytocin 0.18ml (final concentration is 0.03 μ/ml) to 60ml tyrode's solution, record after administration above-mentioned identical index value in 25min.The solution in ware is held in emptying, with tyrode's solution flushing 2-3 time, then inject 60ml tyrode's solution (37 DEG C ± 0.5 DEG C) to holding in ware, balance also records 20-25min, hold in ware and inject 10 μ/ml oxytocin 0.36ml (final concentration is 0.06 μ/ml) to 60ml tyrode's solution again, record after administration above-mentioned identical index value action effect value in 25min.
Change 2 times flesh bar, repeat 2 above-mentioned steps with method, record identical index value action effect value.
Stachydrine+choline group: first observed and recorded is the tension force 20-25min of flesh bar contraction frequency, contraction wave mean amplitude of tide, contraction wave interval average duration and smooth muscle under normal circumstances.Hold in ware and inject 20mg/ml concentrated solution 1.5ml (final concentration is 0.5mg/ml) to 60ml tyrode's solution, record after administration above-mentioned identical index value in 25min.The solution in ware is held in emptying, with tyrode's solution flushing 2-3 time, then inject 60ml tyrode's solution (37 DEG C ± 0.5 DEG C) to holding in ware, balance flesh bar also records 20-25min, hold in ware and inject 20mg/ml concentrated solution 3ml (final concentration is 1.0mg/ml) to 60ml tyrode's solution again, record after administration above-mentioned identical index value action effect value in 25min.
Change 2 times flesh bar, repeat 2 above-mentioned steps with method, record identical index value action effect value.
Choline group, the administration of stachydrine group and the same stachydrine+choline of test method group.
Dosage setting and the grouped table of Experiment on Function of table 1 to guinea pig in vitro uterine smooth muscle in puerperal
The comparison (± s, n=3) of isolated uterine smooth muscle frequency, amplitude before and after table 2 administration
Note: with comparison before administration, " * " p < 0.05; " * * " p < 0.01.
Give after 0.18ml oxytocin (0.03u), the uterine myometrium curve significant change that system is traced, is mainly that shrinkage amplitude increases, strength increase.4.57 ± the 1.68g of amplitude before by administration is increased to 7.03 ± 1.82g after administration, and the two relatively has significant difference (P < 0.05).Give after 0.36ml oxytocin (0.06u), significantly shrinking appears in uterine smooth muscle, its intensity, amplitude are all compared with increasing before administration, 4.57 ± the 1.68g of amplitude before by administration is increased to 6.42 ± 1.14g after administration, and the two relatively has significant difference (P < 0.05).
Give after 1.5ml stachydrine+choline (both weight ratios are 1: 1, altogether 30mg), the uterine myometrium curve significant change that the system of observing is traced, is mainly that shrinkage amplitude increases, strength increase.Amplitude is increased to 4.31 ± 0.94g after administration by 2.87 ± 0.75g before administration, and the two is no difference of science of statistics (P > 0.05) relatively.(both weight ratios are 1: 1 to give 3.0ml stachydrine+choline, 60mg altogether) after, significantly shrinking appears in uterine smooth muscle, its intensity, amplitude are all compared with increasing before administration, amplitude is increased to 4.57 ± 1.25g after administration by 2.87 ± 0.75g before administration, the two relatively has significant difference (P < 0.05), and 0.81 ± 0.77 time/min of frequency before by administration reduces to 0.40 ± 0.36 time/min, the two is no difference of science of statistics (P > 0.05) relatively.
Give after 1.5ml choline (30mg), the uterine myometrium curve that the system of observing is traced is without significant change.Amplitude is increased to 2.64 ± 0.99g after administration by 2.14 ± 0.98g before administration, and the two is no difference of science of statistics (P > 0.05) relatively.Give after 3.0ml choline (60mg), uterine smooth muscle is without obvious contraction, amplitude is increased to 2.97 ± 1.44g after administration by 2.14 ± 0.98g before administration, the two is no difference of science of statistics (P > 0.05) relatively, and 0.16 ± 0.11 time/min of frequency before by administration is increased to 0.98 ± 1.53 time/min, the two is no difference of science of statistics (P > 0.05) relatively.
Give after 1.5ml stachydrine (30mg), the uterine myometrium curve that the system of observing is traced is without significant change.Amplitude is increased to 3.43 ± 1.12g after administration by 3.16 ± 0.85g before administration, and the two is no difference of science of statistics (P > 0.05) relatively.Give after 3.0ml stachydrine (60mg), uterine smooth muscle is without obvious contraction, amplitude is increased to 3.51 ± 0.97g after administration by 3.16 ± 0.85g before administration, the two is no difference of science of statistics (P > 0.05) relatively, and 0.63 ± 0.57 time/min of frequency before by administration is increased to 0.76 ± 0.72 time/min, the two is no difference of science of statistics (P > 0.05) relatively.
The pregnant Cavia porcellus tension force of table 3, intensity, frequency, amplitude variations analysis (
n=3)
Note: with positive controls comparison, " * " p < 0.05; " * * " p < 0.01; With the comparison of stachydrine+choline group, " # " p < 0.05; " ## " p < 0.01;
Positive controls and stachydrine+choline group relatively have significant difference (p < 0.05) in intensity, amplitude variations level, after positive controls administration, intensity, amplitude variations level, compared with the obvious rising of other each groups, relatively have significant difference (p < 0.01) with it.
Under this experimental condition, from test data analyzer, isolated uterine smooth muscle is administered twice by Concentraton gradient, positive reference substance (oxytocin) shows obvious contraction to isolated uterine smooth muscle, stachydrine+choline group has stronger contraction to isolated uterine smooth muscle, choline, stachydrine show certain contraction in this concentration range to isolated uterine smooth muscle, choline and stachydrine have synergism to isolated uterine smooth muscle contraction.
The impact of embodiment 2 on rat commotio retinae metrorrhagia amount
Rat is mated to copulation, continuous 4 days in female, male 2: 1 ratios.Carry out vaginal smear examination morning every day, the female Mus that has sperm is taken out, and as the 1st day (d1) of gestation.Random packet is raised by date.Totally 70 of pregnant rats, are divided into 7 groups: 10 of normal pregnancy groups, 10 of model group, 10 of stachydrine groups, 10 of leonurine groups, 10 of stachydrine+choline groups, 10 of leonurine+choline groups, 10 of choline groups.In addition, get 10 not the female Mus of copulation as blank group.Except normal pregnancy group and blank group, all the other each group rats are in the 7th day at 9 o'clock in (d7) morning of gestation and at 6 o'clock in afternoon gavage mifepristone (0.83mg/ml respectively, 1ml/100g) and misoprostol (10 μ g/ml, 1ml/100g); Normal pregnancy group, blank group gavage give isopyknic distilled water.Insert one of quantitative sterilized cotton ball in intravaginal simultaneously, the heavy 85-90mg of cotton balls, half side with plastic sheeting parcel, leak outside and backflow with urine with resistant to blood.Gestation is put into the airtight stored refrigerated of plastic bag respectively at 9 o'clock in the morning and at 6 o'clock in afternoon cotton balls being taken out on 8th, changes a new cotton balls in intravaginal simultaneously, every day continuous above be operated to the 14th day (d14).Each group of second day (d8) after gavage mifepristone and misoprostol starts gavage and gives trial drug, successive administration 7 days once a day, and wherein stachydrine group gives stachydrine aqueous solution with 0.5mg/ml concentration according to 1ml/100g rat body weight; Leonurine group gives leonurine aqueous solution with 0.5mg/ml concentration according to 1ml/100g rat body weight; Stachydrine+choline group gives stachydrine and aqueous choline base solution with stachydrine 0.5mg/ml and choline 0.5mg/ml concentration according to 1ml/100g rat body weight respectively; Leonurine+choline group gives leonurine and aqueous choline base solution with leonurine 0.5mg/ml and choline 0.5mg/ml concentration according to 1ml/100g rat body weight respectively, and choline group gives aqueous choline base solution with 0.5mg/ml concentration according to 1ml/100g rat body weight.After last administration 24 hours, with hemoglobin straw in tail vein blood 0.02ml.
Metrorrhagia quantitative determination
Tail vein 0.02ml adds 5%NaOH aqueous solution 4ml, mixes stand-by.The uterus cotton balls of collection is placed in respectively in flask, soaks extruding with 5%NaOH aqueous solution 15ml and wash cotton balls bloodstain by rubbing with the hands, get 5ml lixiviating solution and filter.Respectively by the lixiviating solution 4ml having filtered, rat tail vein blood 5%NaOH aqueous solution 4ml, and using 5%NaOH aqueous solution as blank, record absorbance A value at ultraviolet spectrophotometer wavelength 546nm place.Metrorrhagia amount is calculated according to following formula:
Metrorrhagia amount (ml)=(tail vein amount × uterus blood lixiviating solution A value × V2)/(tail vein A value × V1)
Wherein V1 is the water-soluble liquid measure of dilution tail vein 5%NaOH used, 4ml;
V2 is the water-soluble liquid measure of lixiviate uterus blood 5%NaOH used, 15ml.
The each group of table 4 rat uterus amount of bleeding
| Group | Number of rats | Metrorrhagia amount (ml) |
| Blank group | 10 | 0.031±0.011 |
| Normal pregnancy group | 10 | 0.035±0.015 |
| Model group | 10 | 0.650±0.087 |
| Stachydrine group | 10 | 0.438±0.117 |
| Leonurine group | 10 | 0.467±0.129 |
| Stachydrine+choline group | 10 | 0.263±0.103 |
| Leonurine+choline group | 10 | 0.316±0.132 |
| Choline group | 10 | 0.589±0.096 |
As can be seen from Table 4, choline can obviously strengthen stachydrine and the uterine hemostasis effect of leonurine to commotio retinae rat.
Embodiment 3
Get stachydrine 15g, choline 5g, adds microcrystalline Cellulose 20g, starch 230g, magnesium stearate 10g, and granulation is pressed into 1000, and sugar coating or film-coat obtain stachydrine and choline tablet.
Embodiment 4
Get leonurine 10g, choline 5g, adds microcrystalline Cellulose 20g, starch 260g, magnesium stearate 10g, and granulation, dresses up 1000 capsules, obtains leonurine and choline capsule.
Embodiment 5
The potash 10g of water intaking Soviet Union, choline chloride 10g, adds microcrystalline Cellulose 20g, starch 300g, magnesium stearate 20g, and granulation, dresses up 1000 capsules, obtains stachydrine and choline chloride capsule.
Embodiment 6
Get stachydrine 5g, leonurine 5g, choline 10g, adds microcrystalline Cellulose 20g, starch 300g, magnesium stearate 15g, and granulation is pressed into 1000, and sugar coating or film-coat obtain stachydrine, leonurine and choline tablet.
Claims (5)
1. a pharmaceutical composition, contains Herba Leonuri alkaloid and choline, and wherein choline is the form of free alkali or the form of choline pharmaceutical salts, and Herba Leonuri alkaloid is selected from stachydrine, leonurine, and the weight ratio of Herba Leonuri alkaloid and choline is 10:1-1:10.
2. pharmaceutical composition claimed in claim 1, wherein choline pharmaceutical salts is selected from choline chloride, succinic acid choline.
3. pharmaceutical composition claimed in claim 2, wherein choline is the form of free alkali.
4. the pharmaceutical preparation that claim 3 pharmaceutical composition is prepared into, is selected from injection, tablet, capsule, pill, granule, oral liquid, powder, unguentum, suppository, liniment, gel.
5. claim 3 pharmaceutical composition is in preparation treatment dysfunctional uterine hemorrhage; Postpartum hemorrhage; Application after artificial abortion, spontaneous abortion in vaginal hemorrhage medicine.
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| CN110123664A (en) * | 2019-05-22 | 2019-08-16 | 中科萱嘉医养(珠海)健康科技有限公司 | A kind of supermolecule composition containing leonurine or inclusion compound and the preparation method and application thereof |
| CN110151620A (en) * | 2019-05-23 | 2019-08-23 | 珠海萱嘉君行健康产业发展有限公司 | A kind of whitening cream and preparation method thereof containing stachydrine fatty acid ion liquid |
| CN115997753B (en) * | 2022-07-14 | 2024-04-05 | 石河子大学 | Application of leonurine in preparation of sheep semen preservation diluent |
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