CN1883545A - A compound nano injection preparation of flavescent sophora root and preparation method thereof - Google Patents
A compound nano injection preparation of flavescent sophora root and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a nano flavescent sophora root preparation for injection and its preparing process, wherein nano carrier is prepared from effective positions of flavescent sophora root and right amount of other auxiliary materials, and can be prepared into liquid injections, powder injections and transfusions.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of compound nano injection preparation of flavescent sophora root and preparation method thereof.
Background technology
Nanometer Chinese medicine mainly is meant what the utilization nanotechnology was made, and particle diameter is less than middle pharmaceutically active ingredient, effective site, former medicine and the compound preparation of 100 nanometers.Living organism is the process of a complexity to absorption, the metabolism of medicine, and it is also closely related with the physical state of said preparation that the pharmacodynamics effect that Chinese medicine preparation produces can not only be belonged to the distinctive chemical composition of medicine.Therefore, the physical state of change pharmaceutical preparation is a kind of effective ways of new drug development.Aspect the change physical state, the unit size that changes medicine is highly effective.Owing to quantum size effect and skin effect, nanoparticle presents novel physical chemistry and biological characteristics when particle size enters nanometer scale.Applying nano technology that Here it is may make pharmaceutically active and bioavailability improve and even produces new characteristic according to the place in Chinese medicine research.
Compare with traditional Chinese medicine, nanometer Chinese medicine has following characteristics: 1. improved the availability of medicine, reduced dosage.2. strengthen the targeting of medicine.3. have slow-release function, the Chinese medicine nanoparticle is carried out certain finishing after, may make Chinese medicine have slow releasing function.4. present new drug effect, widen former medicine indication, when Chinese medicine is machined to nano-scale,, thereby can make Chinese medicine present the function that makes new advances because effects such as its quantum size cause the change of its physics, chemical characteristic.5. enrich the dosage form selection of Chinese medicine, promote traditional route of administration.
Problem below nanotechnology at present exists in Chinese medicine research.First, the preparation difficulty of nanometer Chinese medicine: though China has prepared some nano level Chinese medicines, because herbal species is various, complicated component, different compositions is owing to the difference of its site of action, mechanism of action and effect emergency requires its size, carrier components and dosage all possible different.Nanometer Chinese medicine should have its a cover quality standard simultaneously, makes it produce standardization.The second, the toxic and side effects of nanometer Chinese medicine: medicine is made nanoparticle, and significant variation has all taken place for its physical property and chemical property, and whether these change has all relevant research report of toxicity to human body.But, whether can participate in directly or, there is no about report as the normal chemical reaction of catalyst upset body because the particularity of nano material except penetrable skin, also can enter in the organelle.In addition, nanometer Chinese medicine can also be by the barrier system of body, and whether it can influence the central nervous system, the growth of the generation of sperm and vigor thereof, fetus etc., and these problems all can't be avoided.The 3rd, Chinese medicine is after nanoscale is pulverized, and nano-particle surface is long-pending to become big, because the activity of nano-particle surface makes them be easy to reunite together, this brings very big difficulty for the collection of nanoparticle and the stability of drug effect thereof.The 4th, cost improves: because the restriction of prior art level and equipment causes the cost of nanometer Chinese medicine in preparation will exceed much than the preparation of Chinese medicine.
The research of nanometer Chinese medicine at present mainly concentrates on and utilizes nanotechnology that the clearer and more definite monomer effective ingredient of minority composition is carried out nanometer to handle and make nanometer formulation, or crude drug directly is ground into nanoscale, nanometer formulation to most of Chinese medicine is studied also seldom, mainly be because middle pharmaceutically active ingredient and effective site particularly in the Chinese medicine compound effective site itself be exactly one " black box ", real effective ingredient or the effective site research that plays pharmacological action itself is exactly a difficult problem in the Chinese medicine, and because the Chinese medicine ingredients more complicated, so it is prepared into difficult more that nanometer formulation need overcome, therefore, Chinese medicine nanometer formulation and technology are medical scientific research worker's important subject.
FUFANG KUSHEN ZHUSHEYE is, and to be raw material with Radix Sophorae Flavescentis, Smilax lanceaefolia Roxb. Var.opaca A.DC. refine the injection of making through science, has clearing away heat-damp and promoting diuresis, removing pathogenic heat from blood and toxic substance from the body, and the effect of removing obstruction for relieving pain is used for the hemorrhage of cancerous pain.The existing good anticarcinogenic effect of FUFANG KUSHEN ZHUSHEYE, effective alleviating pain again, studies show that FUFANG KUSHEN ZHUSHEYE not only to cancerous pain, carcino-matous hemorrhage, to improve patient's life quality effective, the effect that the tumor body is dwindled.Have the slight stimulation but FUFANG KUSHEN ZHUSHEYE is used except the part in clinical practice, to also have dizziness, constipation, feel sick, the report of untoward reaction generation such as allergy, anaphylactic type and delayed type two classes are arranged, also to occur shiver with cold, hyperpyrexia infusion reaction.Its ingredient poor stability of FUFANG KUSHEN ZHUSHEYE, matrine and oxymatrine twenty percent branch take place to transform mutually in the long term store process, and this writes quality control and the clinical practice that has all influenced FUFANG KUSHEN ZHUSHEYE.
Patent (application number 01102554) discloses a kind of " nano medicine ' Compound Kushen ' and preparation method thereof ", and this method is prepared the nano raw material of each medicine by proportioning, and the preparation method practicality is relatively poor.
Summary of the invention
For these reasons, research worker of the present invention is through lot of experiments, the compound light-yellow sophora root effective site that extraction is obtained adds an amount of carrier and adopts process of the present invention to be prepared into nano injection formulation, the inventive method is easy, be easy to big production, the preparation particle diameter for preparing reaches nanoscale, adopt the nanometer formulation drug loading of the inventive method preparation big, good stability, and can significantly improve the targeting of medicine to tumor cell, and pharmacological evaluation shows compound nano injection preparation of flavescent sophora root more remarkable treatment effect of the present invention, targeting is good, and zest is little, and safety is good.
The present invention aims to provide a kind of stable, safety, good effect, has the compound nano injection preparation of flavescent sophora root of targeting.
The present invention also provides the preparation method of above-mentioned compound nano injection preparation of flavescent sophora root.
The present invention and FUFANG KUSHEN ZHUSHEYE relatively is characterized in that adopting technology of the present invention that compound light-yellow sophora root is prepared into the preparation that reaches nanometer particle size, adopt the nanometer formulation of the inventive method preparation to have significant targeting.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) the preparation prescription weight portion consists of: compound light-yellow sophora root effective site 2-5 part, carrier 10-20 part.
(2) preparation of compound light-yellow sophora root effective site: extract precipitate with ethanol according to the method for making under the 14 FUFANG KUSHEN ZHUSHEYE item of " Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation fascicle, hydraulic pressure concentrated and vacuum drying after medicinal liquid reclaimed ethanol, obtained compound light-yellow sophora root effective site of the present invention.
(3) method one, get compound light-yellow sophora root effective site, emulsifying agent, the lipid of recipe quantity, mixing, heating and melting, polysorbate-20 or 60 is added wherein, mix with 70 ℃ distilled water, stir and be prepared into microemulsion, 65 ℃ microemulsion is poured in the syringe that can be incubated and be incubated 15 minutes, under the mechanical agitation condition, in certain hour, the microemulsion of heat is joined in the cold distilled water, promptly get drug suspension.
Method two, get compound light-yellow sophora root effective site, emulsifying agent, the lipid of recipe quantity, be heated to 80 ± 5 ℃, the aqueous solution that under stirring condition, adds an amount of uniform temp glycerol and poloxamer, make thick breast, under 80 ± 5 ℃ of conditions, carry 40MPa pressure stimulating milk secretion even 5 times, be cooled to room temperature rapidly and form the principal agent suspension with the high pressure dispersing emulsification machine.
Method three, take by weighing emulsifying agent by prescription, add a small amount of Tween 80, in the distilled water of 70 ± 5 ℃ of high-speed stirred condition addings, treat complete fusion as water, take by weighing lipid again and add recipe quantity compound light-yellow sophora root effective site, heating and melting is as oil phase, oil phase is slowly added aqueous phase, and continue to stir ultra-sonic dispersion after 1 hour: the chamber is steady, frequency 45-50Hz, ultrasonic 5-8 minute, be cooled to room temperature rapidly and form the principal agent suspension.
Method four, get compound light-yellow sophora root effective site, lipid and acetone add in the container in right amount, the ultrasonic emulsifying agent that makes abundant dissolving add recipe quantity, slight fever makes the melt into organic facies, other gets emulsifying agent and is dissolved in the suitable quantity of water, constitute water, organic facies under stirring, (1000r/min) is injected 75 ± 2 ℃ of aqueous phases, continue heated and stirred 4h, organic solvent is evaporated fully and system is concentrated, the translucent system of gained is stirred the aqueous phase that following (1000r/min) is dissolved in 0-2 ℃ fast, continue to stir 2 hours, promptly get the principal agent suspension.
(4) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, and stirs evenly, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, stir evenly, add sodium chloride or glucose accent etc. and ooze, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add excipient, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, preparation cost invention compound light-yellow sophora root powder injection formulation.
Carrier of the present invention mainly comprises lipid and emulsifying agent two parts.
The used lipid of the present invention can be: fatty acid glycerine esters (comprise glyceryl tristearate, tripalmitin, myristin, trilaurin, three climb over a wall acid glyceride, Witepsol W35, Witepsol H35, Witepsol H42, glyceryl monostearate) and fatty acid (as stearic acid, Palmic acid) etc.
The used emulsifying agent of the present invention can be phospholipid (comprising soybean lecithin, Ovum Gallus domesticus Flavus lecithin and phosphatidylcholine etc.), Pluronic F68, poloxamer, polysorbate, cholate, alevaire etc.
Nano injection formulation of the present invention can be nanometer aqueous injection, nano powder injection, nanometer infusion preparation.
Nanometer aqueous injection of the present invention, nanometer infusion solution add a small amount of PVP (polyvinylpyrrolidone), can improve stability of formulation, prevent the nanoparticle gathering.
The excipient of nanometer powder injection formulation of the present invention is one or both in mannitol, glucose, lactose, dextran, the glucosan.
The used nano-carrier of preparation of the present invention can also prepare by the following method:
With the oil solution (one or more in paracyanogen base alkyl acrylate, polylactic acid, polylactide-co-glycolide, chitosan, the gelatin) of compound light-yellow sophora root effective site, mix with dehydrated alcohol, shake up, get clear solution; Water is the aqueous solution (pH value about 6) of 0.5% nonionic surfactant Pluronic F68, biphasely be 20 ℃, oil phase is injected the aqueous phase of electromagnetic agitation by silica gel tube or fine needle head, form nanocapsule immediately, solution for vacuum is evaporated to about 1/5 of original volume, filter with glass sand hourglass (9-15 μ m), promptly.
The used above preparing carriers technology of the present invention is that we are through lot of experiments and preferred result, we have adopted a lot of nanotechnology technologies and have compared in research process, the technology that has is difficult to be prepared into Nano medication, even and if the technology that has is prepared into Nano medication, do not reach the targeting effect of preparation of the present invention yet.
Two, quality testing
Instrument: H-7000 type transmission electron microscope instrument (Japanese Hitachi company); Zetamaster photon correlation spectrometer (Britain Malvern company); LC-10A high performance liquid chromatograph (day island proper Tianjin); TGL-18G type table model high speed centrifuge.
Detect foundation: with reference to the method under 2005 editions two appendix XIX E of the Pharmacopoeia of the People's Republic of China guideline item.
1, morphologic observation and particle diameter
Nano medication of the present invention is carried out morphologic observation under transmission electron microscope, as seen be spherosome, size is more even, smooth surface, no adhesion.Measured 500 according to the microphotograph of Nano medication, mean diameter is 37.6nm, and maximum particle diameter is 68.5nm, and minimum grain size is 22.0nm, and particle size distribution meets normal distribution law.
2, envelop rate and drug loading are measured
Carry out assay with reference to content of matrine assay method under the FUFANG KUSHEN ZHUSHEYE item, and with following formula computational envelope rate and drug loading: envelop rate (%)=(dosage-free drug amount)/dosage * 100%; Weight * 100% of drug loading (%)=(dosage-free drug amount)/Nano medication.The result: in the average envelop rate of matrine is 95.7.%, and drug loading can reach 10%-25%.
3, study on the stability
Nano medication of the present invention is placed in the bottle sealing respectively.In the environment of refrigerator (3-5 ℃), room temperature (20-25 ℃) and 37 ℃ (RH75%), place, in 0,1,2 with observe March such as outward appearance, size, redispersibility of Nano medication etc.The result there is no significant change, and it is good that the Nano medication redispersibility under 3 kinds of conditions keeps, the generation of no polymerism.The results are shown in Table 1.
Table 1 stability experiment result
| The placement condition | Observation index | Time (moon) | |||
| 0 | 1 | 2 | 3 | ||
| 3-5℃ | Mean diameter (nm) | 37.5 | 37.8 | 37.2 | 37.6 |
| 20-25℃ | Mean diameter (nm) | 37.0 | 38.5 | 37.8 | 37.5 |
| 37℃(RH75％) | Mean diameter (nm) | 37.9 | 37.5 | 37.4 | 37.2 |
4, accelerated tests assay
FUFANG KUSHEN ZHUSHEYE (Shanxi Jin Jing Pharmaceutical Co., Ltd); Compound nano injection preparation of flavescent sophora root of the present invention (by preparation technology's preparation of the present invention, by Tianzhijiao Medication Development Co., Ltd., Guangdong's prepared in laboratory); Above preparation is put 40 ℃ respectively, placed 6 months under the RH75% condition, measure content of matrine in the preparation respectively, investigate the variation (was 100% calculating with 0 month content) of Compound Kushen ' content under the acceleration environment.The results are shown in Table 2.
Table 2 preparation stability test assay result
| Sample | 0 month | January | February | March | June |
| FUFANG KUSHEN ZHUSHEYE compound light-yellow sophora root nanometer aqueous injection compound light-yellow sophora root nano powder injection compound light-yellow sophora root nanometer infusion solution | 100％ 100％ 100％ 100％ | 97.3％ 99.5％ 99.3％ 99.6％ | 94.1％ 98.0％ 98.6％ 98.3％ | 90.5％ 96.4％ 96.7％ 96.5％ | 87.0％ 95.7％ 96.1％ 96.0％ |
Result of the test shows that the matrine content of FUFANG KUSHEN ZHUSHEYE in the accelerated tests process descends obviously, and adopt the compound nano injection preparation of flavescent sophora root of the inventive method preparation to change less, measure the particulate matter of above-mentioned preparation simultaneously, find that FUFANG KUSHEN ZHUSHEYE particulate matter number and compound light-yellow sophora root nanometer formulation of the present invention comparison particulate matter in storage have remarkable increase trend, and compound light-yellow sophora root nanometer formulation number of the present invention is few and storage in constant substantially, illustrate that the preparation method of compound light-yellow sophora root nanometer formulation of the present invention has significantly improved the quality and the stability of preparation, has important and practical meanings.
Three, pharmacology and targeting experiment
Reagent and animal: FUFANG KUSHEN ZHUSHEYE (Shanxi Jin Jing Pharmaceutical Co., Ltd); Compound nano injection preparation of flavescent sophora root of the present invention (by preparation technology's preparation of the present invention, by Tianzhijiao Medication Development Co., Ltd., Guangdong's prepared in laboratory); The Wistar rat, body weight 180-220g; Healthy mice, body weight 18-22g; Tumor strain: mice S
180, rat liver cancer H22 (Guangzhou Experimental Animal Center).
1. to transplanted hepatoma H
22Influence and targeting
The hepatocarcinoma H of aseptic extraction inoculation back 7d
22Tumor-bearing mice ascites, add 4 times of amount normal saline mixings, it is subcutaneous to be inoculated in mice right fore axillary fossa place immediately, every inoculation 0.2ml, inoculation back 24h random packet, tail vein injection administration, dosage is 8g crude drug/kg, the administration volume only is all 0.2ml/, and matched group gives the equivalent normal saline, administration every day 1 time, successive administration 10d, 24h takes off neck execution mice after the last administration, and the subcutaneous tumors piece is peeled off in the also carefulness of weighing, and takes by weighing tumor in the EM50 electronic balance and weighs, and calculating tumour inhibiting rate, get tumor cell then in tissue: normal saline is the ratio homogenate of 1: 1.5 (W/V), and centrifugal 10min (2000rpm) gets supernatant and measures content of matrine with the HPLC method.1h gets the matrine content in the hematometry serum after the while last administration.The results are shown in Table 3, table 4.
Table 3 couple transplanted hepatoma H
22The influence of mice
| Group | The The average survival time natural law | Increase in life span (%) |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 13.2±1.1 17.2±2.6 24.1±5.0 | 30.3 ** 63.4 **ΔΔ |
Annotate: compare with the normal saline group
*Compare with positive controls P＜0.01
The Δ ΔP＜0.01
Table 4 couple transplanted hepatoma H
22Targeting
| Group | Matrine in the serum (μ g/ml) | Matrine content in the tumor cell (μ g) |
| FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 0.0086 0.0085 | 0.45 4.87 |
The result shows that compound nano injection preparation of flavescent sophora root of the present invention can prolong transplanted hepatoma H
22The life span of mice has than the better pharmacological action of FUFANG KUSHEN ZHUSHEYE, and nano injection formulation of the present invention and FUFANG KUSHEN ZHUSHEYE relatively effective ingredient concentration in serum are suitable, and hepatocarcinoma H
22Significantly increase in the tumor cell, show that nano injection formulation of the present invention is to hepatocarcinoma H
22Tumor cell has targeting preferably.
2. to mice S
180Function of tumor
2.1 to mice S
180Tumor growth inhibitory action and targeting
Get and inoculate the mice S that goes down to posterity
180, in homogenizer, add normal saline, make mice S
180The tumor homogenate, again with normal saline 1: 3 dilution, getting 0.2ml then, to inject oxter, a mice left side subcutaneous, weighed in 24 hours, administration group mice tail every day intravenously administrable once, dosage is 8g crude drug/kg, the administration volume only is all 0.2ml/, and matched group gives the equivalent normal saline, totally 7 days.Mice is put to death in drug withdrawal next day, the subcutaneous tumors piece is peeled off in the also carefulness of weighing, taking by weighing tumor in the EM50 electronic balance weighs, and calculating tumour inhibiting rate, with the tumor piece after weighing in tissue: normal saline is the ratio homogenate of 1: 1.5 (W/V), centrifugal 10min (2000rpm) gets supernatant and measures content of matrine with the HPLC method.1h gets the matrine content in the hematometry serum after the while last administration.The result sees Table 5 respectively, table 6.
Table 5 couple mice S
180The tumor growth inhibitory action
| Group | Tumor body weight (mg) | Tumour inhibiting rate (%) |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 1.5123 1.0104 0.7355 | 33.2 ** 51.4** ΔΔ |
Annotate: compare * * P＜0.01 with the normal saline group, compare with FUFANG KUSHEN ZHUSHEYE
The Δ ΔP＜0.01
Table 6 couple mice S
180The targeting of tumor
| Group | Matrine in the serum (μ g/ml) | Matrine content in the tumor cell (μ g) |
| FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 0.086 0.087 | 0.52 5.10 |
The result shows that compound nano injection preparation of flavescent sophora root of the present invention can significantly suppress S
180Tumor growth has than the better pharmacological action of FUFANG KUSHEN ZHUSHEYE, and nano injection formulation of the present invention and FUFANG KUSHEN ZHUSHEYE relatively effective ingredient concentration in serum are suitable, and S
180Significantly increase in the tumor cell, show that nano injection formulation of the present invention is to S
180Tumor cell has targeting preferably.
2.2 to lotus tumor S
180The influence of mouse death rate and time-to-live
Get and inoculate the mice S that goes down to posterity
180, in homogenizer, add normal saline, make mice S180 tumor homogenate, again with normal saline 1: 3 dilution, getting 0.2ml then, to inject oxter, a mice left side subcutaneous, a week behind inoculated tumour, promptly the 8th day begins by 1.1 method administrations, allow its natural death, treat the whole death of control animals after, mortality rate relatively, and the time-to-live difference of 90 days each treated animals of comparison, if administration group and matched group, 20 of every group of mices the results are shown in Table 7.
Table 7 pair mouse death rate and the influence of time-to-live
| Group | Death toll (%) | Mortality rate (%) | Mean survival time (my god) | Increase in life span (%) |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 20 14 7 | 100 70* 35* Δ | 31.5±1.9 57.5±4.0 72.1±7.6 | 82.5** 128.9** Δ |
Annotate: compare * * P＜0.01 with the normal saline group, compare with the FUFANG KUSHEN ZHUSHEYE group
ΔP＜0.05
The result shows that compound nano injection preparation of flavescent sophora root of the present invention can significantly reduce the tumor-bearing mice mortality rate, prolongs the tumor-bearing mice time-to-live, relatively acts on more remarkable with FUFANG KUSHEN ZHUSHEYE.
3. analgesic activity
3.1 the mice hot plate is caused the influence of pain effect
Get 30 of mices, male and female half and half, be divided into 3 groups at random, every group 10, be normal saline group, FUFANG KUSHEN ZHUSHEYE group, compound nano injection preparation of flavescent sophora root group of the present invention, dosage is 8g crude drug/kg, the administration volume only is all 0.2ml/ mutually, the blank group gives the equivalent normal saline, successive administration 3 days, 1h is individually fixed in each Mus in 55 ± 0.5 ℃ the hot-plate instrument, to lick the indicator reaction of metapedes as " pain " after the last administration, mice the results are shown in Table 5 to the hot plate response time bitterly after observing administration.
3.2 the influence of the writhing response that Dichlorodiphenyl Acetate causes
Get mice, male and female half and half, grouping and medication are with 3.1, successive administration 3 days, and 1h after the last administration, lumbar injection 0.6% acetum 0.2ml/20g body weight is observed the mouse writhing number of times in the 10min, the results are shown in Table 8.
Table 8 analgesic test result
| Group | Pain threshold (s) | |
| The hot plate pain response time (s) | Turn round the body number of times | |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 11.7±4.2 17.2±4.5 * 20.4±5.2 ** | 28.5±5.6 18.7±4.1 * 12.5±2.0 ** |
Annotate: compare with the normal saline group:
*P＜0.05
*P＜0.01
Result of the test shows that compound nano injection preparation of flavescent sophora root of the present invention has analgesic activity preferably, and wherein the analgesic activity of compound nano injection preparation of flavescent sophora root of the present invention is more more remarkable than the effect of FUFANG KUSHEN ZHUSHEYE with compound recipe.
4. anastalsis
4.1 influence to the mice bleeding time
Get mice, male and female half and half, grouping and medication are with 3.1, successive administration 3 days, 30min cuts off the most advanced and sophisticated 3mm of mouse tail place after the last administration, treats that blood flows out voluntarily to pick up counting, inhale to dehematize with filter paper every 30s and drip 1 time, till blood flow stops (filter paper suction depletion of blood) voluntarily, calculate the bleeding time, the results are shown in Table 9.
The influence in table 9 pair mice bleeding time
| Group | Bleeding time (s) |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 12.7±3.4 8.2±1.5 * 5.5±1.1 ** |
Annotate: compare with the normal saline group:
*P＜0.05
*P＜0.01
Result of the test shows that compound nano injection preparation of flavescent sophora root of the present invention has significant anastalsis, and is better with FUFANG KUSHEN ZHUSHEYE group comparative effectiveness.
5. antiinflammatory action
5.1 influence to mouse ear caused by dimethylbenzene xylene inflammation
Get 30 of mices, male and female half and half, grouping and medication are with 3.1, successive administration 3 days, 30min after the last administration is applied to mice left side ear with dimethylbenzene 0.02ml, and mice is put to death in dislocation behind the 1h, cuts two ears, punching is weighed, and is the swelling degree with left ear and auris dextra sheet weight difference, the results are shown in Table 10.
Table 10 pair mouse ear caused by dimethylbenzene xylene inflammation influence the result
| Group | Swelling degree difference (mg) |
| Normal saline group FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root group of the present invention | 7.8±1.3 5.1±1.2 * 3.6±1.0 ** |
Annotate: compare with the normal saline group:
*P＜0.05
*P＜0.01
The result shows that compound nano injection preparation of flavescent sophora root of the present invention has good antiinflammatory action, and relatively its antiphlogistic effects is better with the FUFANG KUSHEN ZHUSHEYE group.
7. blood vessel irritation is investigated
Get 8 of rabbit, divide equally 2 groups at random, every group 4, respectively at left ear rabbit is placed holder, and head is fixed with a rabbit fixer, with ethanol with skin degerming after, in right side auricular vein injection FUFANG KUSHEN ZHUSHEYE and compound nano injection preparation of flavescent sophora root of the present invention, the normal saline of injecting same volume in the opposite side corresponding position is injected continuous 1 week every day 1 time in contrast, observe the reaction of rabbit ear edge vein, observe the injection site blood vessel every day and have or not rubescent, edema, have or not oozing of blood on every side, touch blood vessel and have or not the hardening phenomenon, left and right sides ear comparative observation.24h after the last administration with sacrifice of animal, takes off two ears, carries out the tissue slice inspection, and the section position is the entad end at inserting needle position, apart from inserting needle position 1-4cm, divides 1-2.5cm and two sections samplings of 2.5-4cm.
Observation index and standards of grading: observational technique comprises perusal and microscopically pathological observation.Observe the variation of administration blood vessel and surrounding tissue thereof, microscopically is observed the pathological change situation that auricular vein has or not thrombosis, endothelial injury and blood vessel surrounding tissue.To every index scoring.1. blood vessel changes.Perusal does not have obvious congested note 0 minute, and mild hyperaemia is rubescent, the clear note of lines 1 minute, and congested rubescent, the unclear note of lines 2 minutes, is aubergine note 3 minutes at severe hyperemia; The complete note of microscopic examination blood vessel endothelium and blood vessel wall 0 minute has endothelial injury note 1 minute, and thromboembolism note 2 minutes are arranged, angiorrhexis note 3 minutes.2. the blood vessel surrounding tissue changes.Perusal does not have obvious edema note 0 minute, slight edema note 1 minute, and obviously the edema note is 2 minutes, serious edema note 3 minutes; The normal note of microscopic examination surrounding tissue 0 minute, edema note 1 minute, hemorrhage note 2 minutes has inflammatory cell infiltration note 3 minutes.Every group of every observation index score of 4 rabbit added up, calculate and respectively organize the average value, see Table 11.
Table 11 irritation test result
| Group | The zest scoring |
| FUFANG KUSHEN ZHUSHEYE group compound nano injection preparation of flavescent sophora root of the present invention | 1.5 0.5 |
By above experimental result as can be known: compound nano injection preparation of flavescent sophora root of the present invention and FUFANG KUSHEN ZHUSHEYE comparison stimulus have obvious improvement.
8. hemolytic toxicity is investigated
The preparation of 2% red blood cell suspension: get rabbit ear edge vein and get blood 10-20ml, put into the conical flask that fills bead, Fibrinogen is removed in jolting 10 minutes, makes to become to take off fine blood.Add the normal saline solution of 10 times of amounts, shake up, centrifugal, remove supernatant, sedimentary erythrocyte reuse normal saline solution washing 2-3 time, when supernatant does not take on a red color till.It is 2% suspension that the erythrocyte of gained is made into concentration with normal saline, promptly.
Test method: get 6 in test tube, add 2% red blood cell suspension and normal saline solution successively by the proportional quantity in the table, mixing was placed 30 minutes in 37 ℃ of calorstats, added not commensurability medicinal liquid (is blank with the 6th pipe) respectively, after shaking up, put in 37 ℃ of calorstats, beginning was observed 1 time every 15 minutes, after 1 hour, observed 1 time every 1 hour, observed altogether 2 hours.The results are shown in Table 12.
Table 12 hemolytic experiment result
| The test tube numbering | 2% red blood cell suspension (ml) | Normal saline solution (ml) | Medicinal liquid (ml) |
| 1 2 3 4 5 6 | 2.5 2.5 2.5 2.5 2.5 2.5 | 2.0 2.1 2.2 2.3 2.4 2.5 | 0.5 0.4 0.3 0.2 0.1 0 |
The result: be as the criterion with the 3rd test tube, each Guan Junwei dyes redness, and microscopically is observed and do not seen that erythrocyte fragmentation is arranged, and not haemolysis of this product is described, safety is good.
9. acute toxicity testing
Get 80 of Wistar rats, male and female half and half.Fasting 24h divides 4 groups at random, 20 every group.Be condensed into identical crude drug concentration, each group is the tail vein injection medicine respectively, and dosage is equivalent to FUFANG KUSHEN ZHUSHEYE 300g crude drug/kg by the conversion of crude drug amount, administration every day 3 times, and continuous 7 days, observe the dead mouse situation, the results are shown in Table 13.
Table 13 acute toxicity testing result
| Group | Number of animals | Death toll | Mortality rate (%) |
| FUFANG KUSHEN ZHUSHEYE group compound light-yellow sophora root nanometer of the present invention aqueous injection compound light-yellow sophora root nano powder of the present invention injection compound light-yellow sophora root nanometer of the present invention infusion solution | 20 20 20 20 | 6 3 4 4 | 30 15 20 20 |
The acute toxicity testing result shows compound nano injection preparation of flavescent sophora root of the present invention and FUFANG KUSHEN ZHUSHEYE, and relatively safety is better.
Brief summary: above The pharmacological results shows that compound nano injection preparation of flavescent sophora root pharmacological action of the present invention significantly is better than FUFANG KUSHEN ZHUSHEYE, and compound nano injection preparation of flavescent sophora root of the present invention has better targeting and safety.
Four, preparation embodiment
Embodiment 1
(1) gets compound light-yellow sophora root effective site 20g, lecithin 50g, glyceryl monostearate 50g, mixing, heating and melting, polysorbate-202g is added wherein, mix with 70 ℃ distilled water, stir and be prepared into microemulsion, 65 ℃ microemulsion is poured in the syringe that can be incubated and be incubated 15 minutes, under the mechanical agitation condition, in certain hour, the microemulsion of heat is joined in the cold distilled water, promptly get drug suspension.
(2) preparation is equipped with
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding sodium chloride accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add mannitol, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 2
(1) gets compound light-yellow sophora root effective site 20g, fabaceous lecithin 50g, stearic acid 60g, mixing, heating and melting, polysorbate-603g is added wherein, mix with 70 ℃ distilled water, stir and be prepared into microemulsion, 65 ℃ microemulsion is poured in the syringe that can be incubated and be incubated 15 minutes, under the mechanical agitation condition, in certain hour, the microemulsion of heat is joined in the cold distilled water, promptly get drug suspension.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding sodium chloride accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add mannitol, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 3
(1) gets compound light-yellow sophora root effective site 30g, lecithin 80g, glyceryl monostearate 90g, be heated to 80 ± 5 ℃, the aqueous solution that under stirring condition, adds uniform temp glycerol 2g and poloxamer 5g, make thick breast, carry 50MPa pressure stimulating milk secretion even 5 times with the high pressure dispersing emulsification machine under 80 ± 5 ℃ of conditions, cooling forms the principal agent suspension rapidly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding sodium chloride accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add mannitol, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 4
(1) gets compound light-yellow sophora root effective site 50g, lecithin 80g, myristin 120g, be heated to 80 ± 5 ℃, the aqueous solution that under stirring condition, adds uniform temp glycerol 3g and poloxamer 5g, make thick breast, carry 50MPa pressure stimulating milk secretion even 5 times with the high pressure dispersing emulsification machine under 80 ± 5 ℃ of conditions, cooling forms the principal agent suspension rapidly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 3g, add the injection water to 50000ml, stir evenly, adding glucose accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add lactose, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 5
(1) gets compound light-yellow sophora root effective site 40g, Pluronic F68 75g, stearic acid 75g, be heated to 80 ± 5 ℃, the aqueous solution that under stirring condition, adds uniform temp glycerol 3g and poloxamer 6g, make thick breast, carry 50MPa pressure stimulating milk secretion even 5 times with the high pressure dispersing emulsification machine under 80 ± 5 ℃ of conditions, cooling forms the principal agent suspension rapidly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding sodium chloride accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add glucose, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 6
(1) gets lecithin 80g, Tween 80 2g, in the high-speed stirred condition adds 70 ± 5 ℃ distilled water, treat complete fusion as water, take by weighing the three acid glyceride 80g that climb over a wall again and add compound light-yellow sophora root effective site 30g, heating and melting is as oil phase, oil phase is slowly added aqueous phase, and ultra-sonic dispersion behind the lasting stirring 1h: the chamber is steady, frequency 45-50Hz, ultrasonic 5-8 minute, promptly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding glucose accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add dextran, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 7
(1) gets compound light-yellow sophora root effective site 20g, stearic acid 90g and acetone 200ml add in the container, ultrasonicly make abundant dissolving, the lecithin 80g that adds recipe quantity, slight fever makes the melt into organic facies, other gets poloxamer 20g and is dissolved in the 250ml water, constitute water, organic facies under stirring, (1000r/min) is injected 75 ± 2 ℃ of aqueous phases, continue heated and stirred 4h, organic solvent is evaporated fully and make system be concentrated to about 500ml, the translucent system of gained is stirred the 100ml water that time (1000r/min) is dissolved in 0-2 ℃ fast, continue to stir 2h, promptly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 4g, add the injection water to 50000ml, stir evenly, adding glucose accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add glucosan, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 8
(1) compound light-yellow sophora root effective site 25g is dissolved in polylactide-co-glycolide 120g, mixes, shake up, get clear solution with the 1000ml dehydrated alcohol; Water: the aqueous solution 3000ml (pH value about 6) that is 0.5% nonionic surfactant Pluronic F68, biphasely be 20 ℃, oil phase is injected the aqueous phase of electromagnetic agitation by silica gel tube or fine needle head, form nanocapsule immediately, solution for vacuum is evaporated to about 1/5 of original volume, filter with glass sand hourglass (9-15 μ m), promptly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 3g, add the injection water to 50000ml, stir evenly, adding sodium chloride accent etc. oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add glucose and lactose, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Embodiment 9
(1) compound light-yellow sophora root effective site 30g is dissolved in paracyanogen base alkyl acrylate 140g, mix with the 1000ml dehydrated alcohol, shake up, clear solution; Water: the aqueous solution 3000ml (pH value about 6) that is 0.5% nonionic surfactant Pluronic F68, biphasely be 20 ℃, oil phase is injected the aqueous phase of electromagnetic agitation by silica gel tube or fine needle head, form nanocapsule immediately, solution for vacuum is evaporated to about 1/5 of original volume, filter with glass sand hourglass (9-15 μ m), promptly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: get above-mentioned suspension, add PVP 2g, add the injection water to 1000ml, stir evenly, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention compound light-yellow sophora root nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, add PVP 3g, add the injection water to 50000ml, stir evenly, add sodium chloride or glucose accent etc. and ooze, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, sterilization, preparation cost invention compound light-yellow sophora root nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add lactose and glucosan, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, 500 bottles of preparation cost invention compound light-yellow sophora root powder injection formulations.
Claims (4)
1, a kind of compound nano injection preparation of flavescent sophora root, it is characterized in that it is Radix Sophorae Flavescentis, Smilax lanceaefolia Roxb. Var.opaca A.DC. to be extracted the compound light-yellow sophora root effective site that obtains be equipped with the nano level ejection preparation that carrier is made, wherein compound light-yellow sophora root effective site 2-5 weight portion, carrier 10-20 weight portion.Its feature is that also it has targeting.
2,, it is characterized in that described nanoscale is 20-70nm according to a kind of compound nano injection preparation of flavescent sophora root of claim 1.
3, compound nano injection preparation of flavescent sophora root according to claim 1 and 2, its preparation method is:
(1) preparation of principal agent suspension
Method one, get compound light-yellow sophora root effective site, emulsifying agent, the lipid of recipe quantity, mixing, heating and melting, polysorbate-20 or 60 is added wherein, mix with 70 ℃ distilled water, stir and be prepared into microemulsion, 65 ℃ microemulsion is poured in the syringe that can be incubated and be incubated 15 minutes, under the mechanical agitation condition, in certain hour, the microemulsion of heat is joined in the cold distilled water, promptly get drug suspension.
Method two, get compound light-yellow sophora root effective site, emulsifying agent, the lipid of recipe quantity, be heated to 80 ± 5 ℃, the aqueous solution that under stirring condition, adds an amount of uniform temp glycerol and poloxamer, make thick breast, under 80 ± 5 ℃ of conditions, carry 40MPa pressure stimulating milk secretion even 5 times, be cooled to room temperature rapidly and form the principal agent suspension with the high pressure dispersing emulsification machine.
Method three, take by weighing emulsifying agent by prescription, add a small amount of Tween 80, in the distilled water of 70 ± 5 ℃ of high-speed stirred condition addings, treat complete fusion as water, take by weighing lipid again and add recipe quantity compound light-yellow sophora root effective site, heating and melting is as oil phase, oil phase is slowly added aqueous phase, and continue to stir ultra-sonic dispersion after 1 hour: the chamber is steady, frequency 45-50Hz, ultrasonic 5-8 minute, be cooled to room temperature rapidly and form the principal agent suspension.
Method four, get compound light-yellow sophora root effective site, lipid and acetone add in the container in right amount, the ultrasonic emulsifying agent that makes abundant dissolving add recipe quantity, slight fever makes the melt into organic facies, other gets emulsifying agent and is dissolved in the suitable quantity of water, constitute water, organic facies under stirring, 1000r/min is injected 75 ± 2 ℃ of aqueous phases, continue heated and stirred 4h, organic solvent is evaporated fully and system is concentrated, the translucent body of gained is tied up to the aqueous phase that is dissolved in 0-2 ℃ under the 1000r/min stirring fast, continue to stir 2 hours, promptly get the principal agent suspension.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation:. get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, and stirs evenly, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, sterilization, preparation cost invention nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, and stirs evenly, and adds sodium chloride or glucose accent etc. and oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add excipient, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, preparation cost invention powder injection formulation.
4, compound nano injection preparation of flavescent sophora root according to claim 1 and 2, its preparation method is:
(1) preparation of principal agent suspension
Compound light-yellow sophora root effective site is dissolved in paracyanogen base alkyl acrylate, polylactic acid, polylactide-co-glycolide, chitosan, the gelatin one or more, mixes, shake up with dehydrated alcohol, clear solution; Water is the aqueous solution of 0.5% nonionic surfactant Pluronic F68 of pH value about 6, biphasely be 20 ℃, oil phase is injected the aqueous phase of electromagnetic agitation by silica gel tube or fine needle head, form nanocapsule immediately, solution for vacuum is evaporated to about 1/5 of original volume, filter with 9-15 μ m glass sand hourglass, promptly.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation:. get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, and stirs evenly, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, sterilization, preparation cost invention nanometer hydro-acupuncture preparation;
The preparation of infusion preparation: get above-mentioned suspension, it is an amount of to add PVP, adds to the full amount of water for injection, and stirs evenly, and adds sodium chloride or glucose accent etc. and oozes, and adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, and sterilization, preparation cost invention nanometer infusion preparation;
The preparation of powder injection formulation: get above-mentioned suspension, add excipient, add the injection water and adjust concentration, adjust pH is 6.0-7.0, with 0.22 μ m filtering with microporous membrane, lyophilization, preparation cost invention nanometer powder injection formulation.
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| CN 200510077496 CN1883545A (en) | 2005-06-24 | 2005-06-24 | A compound nano injection preparation of flavescent sophora root and preparation method thereof |
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