Isoglycyrrhiza acid magnesium preparation for vein and preparation method thereof
Technical field
The invention belongs to field of medicine preparations, relate in particular to low capacity vein Isoglycyrrhiza acid magnesium injection and high capacity vein magnesium isoglycyrrhetate infusion preparation and preparation method thereof.
Background technology
The glycyrrhizic acid that mainly contains the α configuration of the glycyrrhizic acid of beta comfiguration and minute quantity in natural plant Radix Glycyrrhizae (Glycyrrhiza Uralensis) rhizome, pass through certain reaction, the glycyrrhizic acid of beta comfiguration can be converted into the glycyrrhizic acid of α configuration, sees patent CN1381462A.
Since the effective ingredient glycyrrhizic acid of Radix Glycyrrhizae in 1948 is found, its research has been deepened continuously.Antiinflammatory that glycyrrhizic acid has, antioxidation, anti-hepatotoxic agent, stabilizing cell membrane, anti-hepatic fibrosis, adjusting immunity, inhibition Ca
2+In stream, prevent apoptosis and increase multiple efficacies such as endogenous steroid generation, be the important mechanisms of its hepatocyte protection effect.
The glycyrrhizic acid preparation is from initial Radix Glycyrrhizae mixed extract, to first generation glycyrrhizic acid preparation glycyrrhizin tablet (low, the erious adverse reaction of bioavailability) and the second filial generation with β body monoammonium glycyrrhizinate be main component SNMC (liver target not by force, easily in fatty tissue, accumulate, safety is relatively poor etc.), all because of its limitations restrict clinical practice.Along with deepening continuously of research, it is found that the less α body glycyrrhizic acid of content in the glycyrrhizic acid mixture because of differently with β body glycyrrhizic acid molecular conformation have that lipotropy is good, anti-inflammatory activity strong, liver target height, untoward reaction advantage such as less.Based on this, fine company had researched and developed third generation glycyrrhizic acid preparation α body and the mixed diammonium glycyrhetate (diammonium glycyrrhizinate) of β body in 1994 honest day.Now, welcome again the 4th generation the glycyrrhizic acid preparation---the birth of magnesium isoglycyrrhetate.
Magnesium isoglycyrrhetate is a kind of noval chemical compound of developing in recent years, and the magnesium salt for the optical isomer α body glycyrrhizic acid of natural glycyrrhizic acid obtains by the Isoglycyrrhiza acid after chemical reaction.The Isoglycyrrhiza acid that in natural high-quality Radix Glycyrrhizae rhizome, contains trace, but, should not directly extract making because content is atomic.Chinese patent " a kind of new chemical compound magnesium isoglycyrrhetate and production method and purposes " (publication number CN1381463A), magnesium isoglycyrrhetate is disclosed first, a kind of conversion ratio that improves natural glycyrrhizic acid is provided, has obtained more economically to be suitable for, technology is simple, the production method of high-quality magnesium isoglycyrrhetate and to the therapeutical effect of hepatopathy.
The magnesium isoglycyrrhetate structure is single 18-αYi Gouti glycyrrhizic acid, and this chemical compound has stronger antiinflammatory, protection liver plasma membrane, detoxifcation, antibiont oxidation and improves the liver function effect.The test of pesticide effectiveness shows, magnesium isoglycyrrhetate has preventive and therapeutic effect to the rat acute hepatic injury that D-Gal causes, can obviously stop ALT (serum alanine aminotransferase) to raise, alleviate hepatocellular degeneration, necrosis and inflammatory cell infiltration, and promote liver cell regeneration; To CCL
4Cause that the rat chronic hepatic injury has the effect that improves liver function, reduces the NO level, alleviates liver tissues inflammatory and fibrosis, in addition Gal/FCA being brought out the mouse immune liver injury also has significant protective effect.
As single 18-αYi Gouti glycyrrhizic acid medicine, magnesium isoglycyrrhetate has multiple pharmacological actions such as stronger antiinflammatory, antioxidation, anti-hepatotoxic agent, stabilizing cell membrane, and liver is the specific target organ of magnesium isoglycyrrhetate.From clinical efficacy, it is fast that ALT speed falls in magnesium isoglycyrrhetate, and effective percentage is up to more than 90%, and safety is good, does not find the common untoward reaction such as water-sodium retention of glycyrrhizic acid preparation in the past.
Chinese patent " magnesium isoglycyrrhetate gel and its production and application " (publication number CN1615886A), disclose a kind of magnesium isoglycyrrhetate external preparation---magnesium isoglycyrrhetate gel and preparation method thereof, this patent also discloses the magnesium isoglycyrrhetate gel can be used for the treatment of psoriasis, chronic eczema dermatitis, contact dermatitis and other abnormality dermatosiss.
Except above-mentioned gel preparation, prior art does not also have to disclose the dosage form that other are suitable for using.In order to improve the water solublity of magnesium isoglycyrrhetate, make patient can be rapidly, safety, medication exactly, we have developed the magnesium isoglycyrrhetate injection type of using for vein.
Summary of the invention
The low capacity vein that the present invention relates to Isoglycyrrhiza acid magnesium injection and high capacity vein magnesium isoglycyrrhetate infusion preparation, drug effect is rapid, and dosage is accurate, and reliable effect has guaranteed clinical drug safety, and has improved the compliance of patient's medication.
The object of the present invention is to provide a kind of stable low capacity vein Isoglycyrrhiza acid magnesium injection and preparation method thereof.
Another object of the present invention is to provide a kind of stable high capacity vein magnesium isoglycyrrhetate infusion preparation and preparation method thereof.
Another object of the present invention is to provide the purposes of magnesium isoglycyrrhetate, and magnesium isoglycyrrhetate can be used for the treatment of hepatopathy, can treat psoriasis, chronic eczema dermatitis, contact dermatitis and other abnormality dermatosiss in addition.
These the two kinds Isoglycyrrhiza acid magnesium preparations that supply vein to use, contained magnesium isoglycyrrhetate content range w/v (W/V) can be 0.001%~30%, preferred magnesium isoglycyrrhetate content range w/v (W/V) is 0.01%~10%.The acid-base value scope is pH6.5~8.Magnesium isoglycyrrhetate is 0.5g~300g in the every 1000ml injection of the Isoglycyrrhiza acid magnesium injection that can exemplify, and magnesium isoglycyrrhetate is 1g~100g in preferred every 1000ml injection.Containing magnesium isoglycyrrhetate in the wherein every 1000ml transfusion of the magnesium isoglycyrrhetate infusion solutions that can exemplify is 0.01~15g, and containing magnesium isoglycyrrhetate in preferred every 1000ml injection is 0.1~10g.
The Isoglycyrrhiza acid magnesium preparation of using for vein need add acidity-basicity regulator, can also add isoosmotic adjusting agent, stabilizing agent or solubilizing agent.The isoosmotic adjusting agent content range is per 1000 milliliters of 5.0g~100g, preferred per 1000 milliliters of 8g~80g.Stabilizing agent, solubilizing agent are the medicament convention amount.Because the water solublity of magnesium isoglycyrrhetate is not fine, by the pH value of acidity-basicity regulator control preparation, it is good to have prepared dissolubility, is beneficial to the preparation of absorption.
Described acidity-basicity regulator is selected from common acid, alkali and/or buffer salt, as sodium hydroxide solution, and ammonia, hydrochloric acid, dilute sulfuric acid, citric acid, acetic acid, maleic acid, lactic acid, phosphoric acid, tartaric acid, Tris, sodium carbonate, sodium bicarbonate, sodium acetate, tertiary sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, ethanolamine, triethanolamine, ethylenediamine, sodium glutamate, boric acid, one or more of Borax.The acid-base value scope is a pH scope 3~11, is preferably 6~11, more preferably pH6.5~8; Wherein acidity-basicity regulator is preferably ammonia, sodium hydroxide solution, more preferably ammonia.
The described Osmolyte regulator that waits is selected from glucose, sodium chloride, potassium chloride, glycerol, mannitol, sorbitol, xylitol, one or more in the sodium lactate Ringer ' solution, preferred sodium chloride.
Described stabilizing agent is antioxidant or antioxidant synergist, is selected from sulphite, as sodium sulfite, and pyrosulfurous acid hydrogen sodium, Potassium acid sulfite, pyrosulfurous acid hydrogen potassium, formaldehyde closes sodium sulfite, sodium thiosulfate, sodium dithionite, 2-hydroxy-2-propane-sulfonic acid sodium salt, hydroxyl Loprazolam sodium; As the L-vitamin C, D-vitamin C, the enediol class of sodium L-ascorbate-2-phosphate; As dithio-erythritol, dithiothreitol dithio, thioglycerol, thiourea, 2 mercapto ethanol, 3-mercaprol, dimercaptopropanol, BAL, 1-sulfo-sorbitol, 5-sulfo--D-glucose, TGA, thiacetic acid., 2-mercaptopropionic acid, mercaptosuccinic acid., the alpha-mercapto N-Propionylglycine, the sulfur-containing compound of 3-thio-2 acid; As hydroquinone, tocopherol, propyl gallate, just two hydrogen guaiacols, butylated hydroxyarisol, the polyatomic phenol of dibutyl cresols; As the L-cysteine, L-methionine, L-lysine, L-valine, L-arginine, L-leucine, L-isoleucine, L-tryptophan, L-glutathion, phenylalanine, alanine, proline, histidine, the amino acids of cystine; As disodium edetate salt, Ca-EDTA sodium salt, 1,2-1,2-diaminocyclohexane tetraacetic acid, diethylenetriamine pentaacetic acid, N-(2-ethoxy)-ethylenediamine triacetic acid trisodium salt, the chelating agen of boric acid.These stabilizing agents can use separately, or several mixing is used.
Described solubilizing agent is selected from amide-type or carbamide analog derivative, amine, amino acids, alcohols, mineral acid, organic acid and its esters, saccharide, saccharic acid salt, saponin, hexamethylenamine, morpholine, sodium cholate, the monovalence soap, aerosol OT, sodium lauryl sulphate, cyclodextrin, polyoxyethylene monostearate, the high-grade aliphatic ester of sucrose, Tween 80, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini.
The low capacity vein can be realized by the following method with the preparation of Isoglycyrrhiza acid magnesium injection:
Magnesium isoglycyrrhetate is added in the water for injection, be stirred to moltenly entirely, use acid-base modifier to regulate acid-base value, if desired, can also comprise adding isoosmotic adjusting agent, stabilizing agent and/or solubilizing agent, get final product through taking off charcoal, coarse filtration, standardize solution, fine straining, embedding, sterilization successively then.
For example its its prescription as follows:
Magnesium isoglycyrrhetate 0.5~300g
Acidity-basicity regulator is an amount of
Water for injection adds to 1000ml
The high capacity vein can be realized by the following method with the preparation of magnesium isoglycyrrhetate transfusion:
Magnesium isoglycyrrhetate is added in the water for injection, be stirred to moltenly entirely, add isoosmotic adjusting agent and be stirred to molten entirely, add and regulate acid-base value, if desired, can also add stabilizing agent, solubilizing agent, get final product through taking off charcoal, coarse filtration, standardize solution, fine straining, embedding, sterilization successively then.
The magnesium isoglycyrrhetate transfusion prescription that can enumerate is:
Magnesium isoglycyrrhetate 0.3g
Acidity-basicity regulator is an amount of
Sodium chloride 9g
Water for injection adds to 1000ml
Containing magnesium isoglycyrrhetate in the every 1000ml injection of optimization formula is 0.1~10g.
Below be pharmacological evaluation:
1. the influence that medicine of the present invention forms mouse tail scale granular layer
ICR is a mice, body weight 18 ± 2g, ♂ ♀ half and half.Be divided into 4 groups at random, every group of 10 mices are divided into low dose group, middle dosage group, high dose group and normal control group, and low dose group is 5mg/kg, and middle dosage group is 10mg/kg, and high dose group is 20mg/kg.Each administration group is pressed 0.1ml/10g IP administration, normal control group mice IP equivalent normal saline, once a day, put to death mice behind the successive administration 15d, get rectangularly, use 10% formalin fixed, paraffin embedding apart from the about 2cm of root place tail skin one, HE dyeing, the afterbody scale of each mice of observation under optical microscope.The granular layer cell person that every scale has connection to embark on journey is called the scale that granular layer is arranged.Count the scale number that granular layer is arranged in per 100 scales, statistical procedures is carried out in the t check between administration group and matched group.
Experimental result: medicine 5mg/kg of the present invention, 10mg/kg, 20mg/kg all can significantly improve mouse tail scale granular layer and form number (P<0.01).Experimental result sees Table 1.
Table 1. medicine of the present invention forms influence ((x ± s n=10) to mouse tail scale granular layer
Compare with the normal control group * p<0.01
2. medicine of the present invention is to the splitted influence of mouse vagina epithelial cell
Getting ICR is the ♀ mice, body weight 18 ± 2g, IP diethylstilbestrol for three days on end, each 0.2mg, mice was divided into 4 groups, model control group in the 4th day, medicine low dose group of the present invention, middle dosage group, high dose group, every group of 10 mices, give each medicine by 0.1ml/10g IP respectively, model control group gives the equivalent normal saline, once a day, and continuous 7 days, last 8:00 administration in the morning, 9:00 begins respectively to organize mice IP colchicine 2.5mg/kg, kills mice behind the 6h, gets the vagina specimen with 10% formalin fixed, paraffin embedding, HE dyeing under optical microscope, is counted the mitosis number in 300 basal cells, convert out the mitosis number in per 100 basal cells, be referred to as mitotic index.Statistical procedures is carried out in the t check between administration group and matched group.
Experimental result: medicine of the present invention can significantly reduce estrogen phase mouse vagina epithelial cell mitotic index (P<0.01).Result of the test sees Table 2.
Table 2. medicine of the present invention is to the splitted influence of mouse vagina epithelial cell ((x ± s n=10)
Compare with model control group * p<0.01
3. medicine of the present invention is to the influence of contact dermatitis
BALB/C mice, body weight 18 ± 2g.Be divided into 4 groups at random, every group of 10 mices, model control group, medicine low dose group 5mg/kg of the present invention, middle dosage group 10mg/kg and high dose group 20mg/kg.Each organizes the mouse web portion unhairing, and 150 μ l are coated with abdominal part sensitization with 3% azolactone dehydrated alcohol-acetone (3: 1) solution, and medicine begins lumbar injection in sensitization the previous day, and once a day, continuous 6 days, model control group gave the equivalent normal saline; After the sensitization the 7th day, be coated with two ear two sides with 20 μ l1% azolactone olive oil, measure before exciting and excite the thickness of back 24h.
Experimental result: the mice auricle swelling (P<0.01) that the remarkable Yi Zhi azolactone of medicine 10mg/kg of the present invention, 20mg/kg energy causes.Result of the test sees Table 3.
Table .3. medicine of the present invention is to the influence (x ± s n=10) of mice contact dermatitis
Compare with model control group * p<0.01
4. to the effect of mice chronic dermatitis-eczema
The ICR mice, body weight 18 ± 2g is divided into 5 groups at random, every group of 10 mices, normal control group, model control group, medicine low dose group 5mg/kg of the present invention, middle dosage group 10mg/kg and high dose group 20mg/kg.Except that the normal control group, each is organized mice and is applied to back sensitization outward with 7%DNCB100 μ l, smears 1%DNCB 5 μ l in the mouse right ear inboard behind the 5d and excites, and excites 1 time every 3d.Each administration group 1d before sensitization, beginning IP administration, every day 1 time, normal control group and model control group give the equivalent normal saline.Each is organized in the 4th and excites back 72h to survey the mice ear degree with slide gauge respectively, repeats to survey 3 times at every turn, averages.Each group was got 6 mouse right ears respectively and is done the pathology section after experiment finished, HE dyeing, and calculating corium soaks into the inflammatory cell number.
Experimental result: medicine 5,10 of the present invention, 20mg/kg can significantly suppress the mice auricle swelling (P<0.01) that the DNCB repetitious stimulation causes, reduce the infiltration inflammatory cell number of ear epidermis and corium, alleviate chronic inflammation.Point out medicine of the present invention that mice chronic dermatitis-eczema is had significant inhibitory effect.Result of the test sees Table 4,5.
Table .4 medicine of the present invention is to the influence (x ± s n=10) of mice chronic dermatitis-eczema
* p<0.05, * * p<0.01, with model control group relatively
Table .5 medicine of the present invention soaks into number of inflammatory cells (x ± s n=6) to mouse ear corium
* p<0.05, * * p<0.01, with model control group relatively
Pharmacodynamics test shows, medicine of the present invention can significantly improve mouse tail scale granular layer and form, significantly inhibition estrogen phase rat and mouse vagina epithelial cell mitosis point out it to have the parakeratosis of correction and antimitotic effect, and psoriasis is had the treatment meaning.Medicine of the present invention can also significantly alleviate the ear swelling degree of contact dermatitis, chronic dermatitis-eczema mice, alleviate the chronic inflammatory disease performance of animal pattern ear epidermis and corium, reduce and soak into the inflammatory cell number, point out its effect, acute and chronic dermatitis, eczema class dermatosis are had auxiliary treatment with antiinflammatory, anti-allergy action and adjusting body's immunity.
Below will be described in detail technical scheme of the present invention, but be not used in restriction the present invention by embodiment.
Embodiment 1
Taking by weighing magnesium isoglycyrrhetate 5.0g adds in the 500ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 7.8 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.8, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 50mg magnesium isoglycyrrhetate.
Embodiment 2
Taking by weighing magnesium isoglycyrrhetate 5.0g adds in the 650ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.0g sodium chloride, stirring and dissolving, regulate pH to 7.7 with ammonia, add 1g needle-use activated carbon insulation absorption 25 minutes then, filtered while hot, be settled to 1000ml with fresh water for injection, ammonia check and correction pH to 7.7, through 0.22 μ m filtering with microporous membrane, embedding is in 1ml, 2ml, 5ml, 10ml, the 20ml ampoule, 100 ℃ * 30min sterilization promptly makes every and contains 5mg respectively, 10mg, 25mg, 50mg, the low capacity vein Isoglycyrrhiza acid magnesium injection of 100mg magnesium isoglycyrrhetate.
Embodiment 3
Taking by weighing magnesium isoglycyrrhetate 10.0g adds in the 550ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, stirring and dissolving, regulate pH to 7.6 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.6, through 0.22 μ m filtering with microporous membrane, embedding is in 20ml, 10ml, 5ml, 2ml, the 1ml ampoule, 100 ℃ * 30min sterilization promptly makes every and contains 200mg respectively, 100mg, 50mg, 20mg, the low capacity vein Isoglycyrrhiza acid magnesium injection of 10mg magnesium isoglycyrrhetate.
Embodiment 4
Taking by weighing magnesium isoglycyrrhetate 5.0g adds in the 600ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 6.5 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 6.5, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 50mg magnesium isoglycyrrhetate.
Embodiment 5
Taking by weighing magnesium isoglycyrrhetate 5.0g adds in the 450ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 8.0 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 8.0, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 50mg magnesium isoglycyrrhetate.
Embodiment 6
Taking by weighing magnesium isoglycyrrhetate 15.0g adds in the 600ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 7.4 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.4, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 150mg magnesium isoglycyrrhetate.
Embodiment 7
Taking by weighing magnesium isoglycyrrhetate 300g adds in the 900ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 7.8 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.8, through 0.22 μ m filtering with microporous membrane, embedding is in the 1ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 300mg magnesium isoglycyrrhetate.
Embodiment 8
Taking by weighing magnesium isoglycyrrhetate 0.5g adds in the 400ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.1g sodium chloride, be stirred to molten entirely, regulate pH to 7.6 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.6, through 0.22 μ m filtering with microporous membrane, embedding is in the 20ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 10mg magnesium isoglycyrrhetate.
Embodiment 9
Taking by weighing magnesium isoglycyrrhetate 100g adds in the 750ml fresh water for injection, heating in water bath and stirring and dissolving, add 9.0g sodium chloride, be stirred to molten entirely, regulate pH to 7.5 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.5, through 0.22 μ m filtering with microporous membrane, embedding is in the 5ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 500mg magnesium isoglycyrrhetate.
Embodiment 10
Taking by weighing magnesium isoglycyrrhetate 5.0g adds in the 550ml fresh water for injection, heating in water bath and stirring and dissolving, regulate pH to 7.6 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5 hour then, filtered while hot is settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.6, through 0.22 μ m filtering with microporous membrane, embedding is in the 10ml ampoule, and 100 ℃ * 30min sterilization promptly makes every low capacity vein Isoglycyrrhiza acid magnesium injection that contains the 50mg magnesium isoglycyrrhetate.
Embodiment 11
Taking by weighing magnesium isoglycyrrhetate 1.5g adds in the 500ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.6 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.6, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in 50ml, 100ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains 75mg, 150mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 12
Taking by weighing magnesium isoglycyrrhetate 2.0g adds in the 550ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.7 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.7, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in 50ml, 100ml, 250ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains 100mg, 200mg, 500mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 13
Taking by weighing magnesium isoglycyrrhetate 0.5g adds in the 450ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.2g sodium chloride stirring and dissolving, regulate pH to 7.5 with ammonia, add 1g needle-use activated carbon insulation absorption 0.4h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.5, through 0.22 μ m filtering with microporous membrane, embedding is in 500ml, 250ml, 100ml, in the 50ml infusion bottle, roll lid, 110 ℃ * 30min sterilization promptly makes and contains 250mg respectively, 125mg, 50mg, the high capacity vein of 25mg magnesium isoglycyrrhetate is infused with magnesium isoglycyrrhetate.
Embodiment 14
Taking by weighing magnesium isoglycyrrhetate 1.5g adds in the 550ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 6.5 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 6.5, through 0.22 μ m filtering with microporous membrane, divide and irritate in 50ml, 100ml infusion bottle, roll lid, 110 ℃ * 30min sterilization promptly gets the high capacity vein that contains 75mg, 150mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 15
Taking by weighing magnesium isoglycyrrhetate 1.5g adds in the 400ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 8.0 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 8.0, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in 50ml, 100ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains 75mg, 150mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 16
Taking by weighing magnesium isoglycyrrhetate 0.01g adds in the 400ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.4 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.4, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in the 500ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains the 5mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 17
Taking by weighing magnesium isoglycyrrhetate 15g adds in the 900ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.7 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.7, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in the 50ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains the 750mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.
Embodiment 18
Taking by weighing magnesium isoglycyrrhetate 0.1g adds in the 400ml fresh water for injection, the heating in water bath stirring and dissolving, add 9.0g sodium chloride stirring and dissolving, regulate pH to 7.8 with ammonia, add 1g needle-use activated carbon insulation absorption 0.5h then, filtered while hot again, be settled to 1000ml with fresh water for injection, with ammonia check and correction pH to 7.8, through 0.22 μ m filtering with microporous membrane, embedding is rolled lid in the 500ml infusion bottle, 110 ℃ * 30min sterilization promptly makes the high capacity vein that contains the 50mg magnesium isoglycyrrhetate respectively and infuses with magnesium isoglycyrrhetate.