CN103536633A - Hydrophilic natural indigo and preparation method thereof - Google Patents
Hydrophilic natural indigo and preparation method thereof Download PDFInfo
- Publication number
- CN103536633A CN103536633A CN201310528983.1A CN201310528983A CN103536633A CN 103536633 A CN103536633 A CN 103536633A CN 201310528983 A CN201310528983 A CN 201310528983A CN 103536633 A CN103536633 A CN 103536633A
- Authority
- CN
- China
- Prior art keywords
- indigo naturalis
- hydrophilic
- indigo
- activator
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention provides hydrophilic natural indigo, which contains a more than 0.3 weight/weight percent activator, wherein the activator simultaneously contains lipophilic hydroxyl groups and hydrophilic groups. The invention also provides a preparation method for the hydrophilic natural indigo. According to the hydrophilic natural indigo, a contact angle of the natural indigo is remarkably reduced, the dispersibility of the natural indigo in water can be effectively improved, the problem that ordinary natural indigo floats at a liquid level, and is difficult to disperse in water is solved, convenience is brought to the use of a patient, the utilization rate of medicinal materials is increased, and high safety is ensured. The preparation method for the hydrophilic natural indigo is convenient, low in cost and favorable for large-scale production, and has a broad application prospect.
Description
Technical field
The present invention relates to a kind of hydrophilic Indigo Naturalis (decoction pieces) and preparation method thereof.
Background technology
Indigo Naturalis is that leaf or the stem and leaf of Acanthaceae Acanthaceous indigo, polygonaceae plant polygonum tinctorium ait., cruciferae isatis flies through the indigo of fermenting, beat, water dried powder, agglomerate or the granule that processing makes.Effect is heat-clearing and toxic substances removing, cooling blood for hemostasis, purging liver-fire, and the diseases such as, erysipelas swollen for epidemic febrile disease intenseness of heat, macule, haematemesis, spitting of blood, pediatric epilepsy scared, skin ulcer, eczema have good effect.Along with to the going deep into of Indigo Naturalis research, its therapeutic domain constantly expands, and is widely used in inside and outside, woman, youngster, contagious department disease.At present the clinical practice usage of Indigo Naturalis is mainly by several below: Chinese patent medicine, external, enter that decoction is taken after mixing it with water and decoct altogether with his medicine after take, wherein in clinicist's prescription, be mostly the latter.
By TCM Document, investigate, the clinical usage of Indigo Naturalis in ancient times mostly is into the loose use of ball, as the precious side > > DAIHESAN of < < health letter, < < medical science is comformed and is recorded > > Indigo Naturalis Pulvis concha Mactrae ball, the blue or green gold of < < Prescriptions for Universal Relief > > is loose, < < Yizong Jinjian > > is invincible loose etc.By to < < Compendium of Materia Medica > >, the prescription of applying at all times 58 Indigo Naturaliss in > > of the < < Indigo Naturalis that < < Chinese medicine voluminous dictionary > > and Huahai are clear, by statistics, find, Indigo Naturalis enters have 8 of decoction decoction, account for overall 13.79%, what enter that decoction takes after mixing it with water has 2, account for overall 3.45%, in 48 remaining sides, be all ball loose, account for overall 82.76%, visible Indigo Naturalis is clinical in ancient times enters the loose use of ball with fado.
In contemporary TCM Pediatrics and other clinical departments, Indigo Naturalis heavy dose enters the diseases such as decoction treatment infantile hyperpyrexia coma, cough due to lung-heat, speckle poison mumps, tumor, sees repeatly special effect.Because the above-mentioned symptoms of child disease are all emergency case, and pill has the feature of " ball person delays also ", and prolonged disintegration, is unwell to first aid, and administration is difficult when patient goes into a coma.Powder is unsuitable for children's's administration, and powder is easily adsorbed in oral cavity, is inhaled in bronchus and lung, causes reflex cough.Decoction can overcome the deficiency of above-mentioned ball powder.Therefore, contemporary clinical traditional Chinese medical science more options Indigo Naturalis enters decoction.In addition the authority < < Chinese medicine voluminous dictionary > > in present age meaning Indigo Naturalis " is taken orally to decoct soup or enter ball and is fallen apart; External is dry to be spread or dresses ".Visible, the usage of tcm clinical practice Indigo Naturalis is just occurring quietly to change at all times.
Indigo Naturalis " body lightweight pine ", granule is less, and proportion is lighter, and specific surface area is larger; In microstructure, the indigo CaCO that waits Organic substance to be adsorbed in a large number porosity and looseness that hydrophobicity is strong
3surface, makes Indigo Naturalis float on the water surface, is difficult for moistening, enters in water.In decoction, the hydrophobicity of Indigo Naturalis makes it float in a large number medicinal liquid surface, and in filter process, loss in a large number, has had a strong impact on actual intake, thereby reduced bioavailability, has caused the waste of herb resource.Therefore, need the deficiency that a kind of new technique overcomes Indigo Naturalis badly, strengthen its hydrophilic, save medical material, serve better tcm clinical practice.
Summary of the invention
The object of the present invention is to provide the novel Indigo Naturalis that a kind of hydrophilic is strong.The present invention also provides the preparation method of hydrophilic Indigo Naturalis.
The invention provides a kind of hydrophilic Indigo Naturalis, described hydrophilic Indigo Naturalis contains activator more than 0.3%w/w; In described activator, contain lipophilic group alkyl and hydrophilic radical simultaneously.
Further, described activator is that alcohols solvent is or/and surfactant.
Further, described alcohols solvent is the alcohols solvent containing C1-10 straight or branched, be preferably the aqueous solvent of methanol, ethanol, dehydrated alcohol, propanol, n-butyl alcohol, ethylene glycol, glycerol, above-mentioned alcohols solvent or the mixture of multiple alcohols, more preferably 95%v/v ethanol; Described surfactant is anion surfactant, cationic surfactant, zwitterionic surfactant or non-ionic surface active agent, is preferably sodium lauryl sulphate, benzalkonium bromide, tween, span, quaternary ammonium compound, lecithin or aminoacid.
The present invention also provides the preparation method of above-mentioned hydrophilic Indigo Naturalis, and operating procedure is as follows: get Indigo Naturalis, in crushing process, pulverize with activator simultaneously, remove residue activator, obtain hydrophilic Indigo Naturalis.
" residue activator " of the present invention refers to and also can be described as free activator by the activator of not being combined with Indigo Naturalis in crushing process, and removal means can adopt conventional solid-liquid isolation method.
The present invention studies and shows, activator can mutually combine with Indigo Naturalis under the mechanical force such as pulverizing, effectively improves the wettability of Indigo Naturalis, thereby improves its dispersibility in water.
Further, described activator is that alcohols solvent is or/and surfactant.
Further, described alcohols solvent is the alcohols solvent containing C1-10 straight or branched, be preferably the aqueous solvent of methanol, ethanol, dehydrated alcohol, propanol, n-butyl alcohol, ethylene glycol, glycerol, above-mentioned alcohols solvent or the mixture of multiple alcohols, more preferably 95%v/v ethanol; Described surfactant is anion surfactant, cationic surfactant, zwitterionic surfactant or non-ionic surface active agent, is preferably sodium lauryl sulphate, benzalkonium bromide, tween, span, quaternary ammonium compound, lecithin or aminoacid.
Wherein, described pulverizing adopts vibromill, ball mill or rod formula grinder to carry out.
Further, the addition of described activator is the more than 3% of Indigo Naturalis weight, is preferably 10～19%.
Further, the time that adopts vibromill to pulverize is 1-60min; Be preferably 20-40min; 23min more preferably.
Further, in vibromill crushing process, charge ratio of media 30-95%, medium material is rustless steel, special stainless steel or pottery, shape of medium is cylindrical, spherical; Amplitude 2-6mm; Operating temperature-160～80 ℃; Preferably, charge ratio of media is 80%, column rustless steel medium, amplitude 4mm, operating temperature-20 ℃.
Further, in ball mill crushing process, rotating speed is 100～300 turn/min, and charge ratio of media is 30～50%, ratio of grinding media to material 10～14:1, and milling time is 80～100min; Preferably, rotating speed is 300 turn/min, and charge ratio of media is 30%, ratio of grinding media to material 12:1, and milling time is 90min.
Further, remove residue activator after, by gained solid at 50 ℃ with inner drying.This drying steps can be removed the part activator of being combined with Indigo Naturalis, dry under said temperature condition, not only can guarantee the dispersibility of Indigo Naturalis, can also reduce the content of adjuvant activator, reduces dosage.
Hydrophilic Indigo Naturalis of the present invention, has significantly reduced the contact angle of Indigo Naturalis, can effectively improve the dispersibility of Indigo Naturalis in water, having overcome common Indigo Naturalis floats on liquid level, is difficult to disperse the problem in water that enters, the patient that is more convenient for uses, and improved the utilization rate of medical material, and safety is good; The preparation method of hydrophilic Indigo Naturalis of the present invention is easy, with low cost, is conducive to large-scale production, has a good application prospect.
Accompanying drawing explanation
Fig. 1 X diffracting spectrum, wherein, A-hydrophilic Indigo Naturalis of the present invention, B-Indigo Naturalis micropowder
Fig. 2 tradition natural indigo decoction piece infrared spectrogram
Fig. 3 Indigo Naturalis micropowder decoction pieces infrared spectrogram
Fig. 4 hydrophilic Indigo Naturalis infrared spectrogram
Fig. 5 red line is Indigo Naturalis micropowder decoction pieces infrared spectrogram, and blue line is hydrophilic Indigo Naturalis infrared spectrogram
The chromatogram of Fig. 6 dehydrated alcohol reference substance solution
The chromatogram of Fig. 7 hydrophilic Indigo Naturalis need testing solution
The chromatogram of Fig. 8 negative control solution (common natural indigo decoction piece)
The impact of the different activators of Fig. 9 on contact angle
The specific embodiment
The preparation of embodiment 1 hydrophilic Indigo Naturalis of the present invention (decoction pieces)
Before Indigo Naturalis is pulverized, moisture control is in 8% left and right.In vibromill crushing process, in Indigo Naturalis, add 95% alcoholic solution of 19% Indigo Naturalis amount to grind, charge ratio of media 80%, column rustless steel medium; Amplitude 4mm; Time 23min; Operating temperature-20 ℃.After grinding finishes, remove unnecessary alcohol, obtain hydrophilic Indigo Naturalis.
The property research of embodiment 2 hydrophilic Indigo Naturaliss (decoction pieces)
(1) preparation of various natural indigo decoction pieces
The preparation of hydrophilic natural indigo decoction piece: embodiment 1 preparation.
The preparation of Indigo Naturalis micropowder decoction pieces: before Indigo Naturalis is pulverized, moisture control is in 8% left and right.In vibromill, pulverize 23min, vibromill charge ratio of media 80%, column rustless steel medium; Amplitude 4mm; Time 23min; Operating temperature-20 ℃.
(2) assay of indigo in traditional natural indigo decoction piece, Indigo Naturalis micropowder decoction pieces and hydrophilic Indigo Naturalis of the present invention, indirubin
Chromatographic condition:
Chromatographic column: global C
18; Mobile phase: methanol: water (70:30); Detect wavelength: 289nm; Column temperature: 30 ℃; Sample size: 10 μ l.
Reference substance solution preparation:
Precision takes indigo reference substance (D-035-110323, Rui Fensi bio tech ltd, Chengdu) 4.24mg, indirubin reference substance (D-025-110622, Rui Fensi bio tech ltd, Chengdu) 2.17mg, add respectively N, dinethylformamide 100ml, ultrasonic 30min, is cooled to room temperature, as stock solution.
The accurate stock solution 12.5ml that draws puts in 25ml brown bottle, with DMF dilution standardize solution, shakes up, and crosses 0.22 μ m microporous filter membrane and get final product.
Need testing solution preparation:
Precision takes Indigo Naturalis powder (granule porphyrize) 0.20160g, Indigo Naturalis micropowder 0.20185g, and Indigo Naturalis modification micropowder 0.20133g, adds respectively DMF 100ml, and ultrasonic 30min, is cooled to room temperature, crosses 0.22 μ m microporous filter membrane and get final product.
In the traditional natural indigo decoction piece of table 1, hydrophilic natural indigo decoction piece and Indigo Naturalis micropowder decoction pieces, result is surveyed in indigo containing
More than experiment shows, tradition natural indigo decoction piece grinds in thinning process pulverizing and add ethanol, indigoly with content indirubin, significant change does not occur, can preliminary judgement, the course of processing of Indigo Naturalis hydrophilic decoction pieces, there is not chemical change significantly in the Organic substance in Indigo Naturalis.
(3) mensuration of particle size distribution
Adopt Ma Erwen laser particle distribution instrument to measure the particle size distribution of Indigo Naturalis micropowder and hydrophilic Indigo Naturalis.Instrument model: Malvern APA2000, analyser: HYDRO2000MU, software: Mastersizer2000; Measurement model: General purpose, range of results: 0.0200 μ m-2000 μ m, sample determination time: 15s, replication 3 times, background correction time: 8s; During mensuration, adopt wet method mode determination, open stirring paddle, turn/min of oar number 2400, ultrasonic power 20MHz, ultrasonic time 30s.The automatic dual pure water distillator of SZ-93A, Shanghai Yarong Biochemical Instrument Plant.
Before experiment, prepare distilled water, ultrasonic degas 20min.Because Indigo Naturalis is not easy to be distributed in water, therefore, before mensuration, first by a small amount of dehydrated alcohol moistening for Indigo Naturalis, then measure.During each measurement, take Indigo Naturalis sample 0.2g, add pure water 7mL, jolting is uniformly dispersed.Each sample sampling 3 times, generates average result automatically.Experimental result is as table 2.
The particle size distribution table of table 2 Indigo Naturalis micropowder and hydrophilic Indigo Naturalis
Use the Student-t check of SPSS17.0 statistical software, the particle diameter of Indigo Naturalis micropowder decoction pieces and hydrophilic natural indigo decoction piece is substantially suitable, the d0.5 of hydrophilic natural indigo decoction piece and d0.9 are slightly larger than Indigo Naturalis micropowder, but there is no significant difference significantly, can think that both particle diameters are suitable.Both hydrophilic differences are because particle diameter difference causes.
(4) mensuration of specific surface area and porosity
Use the full-automatic specific surface area of TriStar3000 and porosity measuring instrument (U.S. Merck & Co., Inc) to measure specific surface area and the porosity of traditional natural indigo decoction piece, Indigo Naturalis micropowder decoction pieces and hydrophilic natural indigo decoction piece.Before mensuration, material is placed in surface plate or weighing botle, and drying under reduced pressure is removed most of moisture, then blows to sample constant weight by ordinary nitrogen.
Table 3 Indigo Naturalis micropowder decoction pieces and hydrophilic natural indigo decoction piece specific surface area and voidage measurement result table
The Student-t check of using SPSS17.0 statistical software, although the specific surface area of Indigo Naturalis micropowder decoction pieces (Lang Gemiao specific surface area and BET specific surface) is slightly larger than hydrophilic natural indigo decoction piece, both do not have significant difference.Can not think that both hydrophilic differences are that difference due to specific surface area causes.
(5) XRD figure spectrum is measured
For investigating the crystalline structure of Indigo Naturalis calcium carbonate in two kinds of process of lapping, whether change, measured respectively the X-ray diffractogram of Indigo Naturalis micropowder decoction pieces and hydrophilic Indigo Naturalis of the present invention.More than being determined at Institute of Analysis of key lab of the building by province and ministry Ministry of Education of Nanchang University of aviation completes.Instrument model: D8ADVANCE(Germany Beuker-axs company produces), 5 ° of-160 ° of scannings of Radix Rumicis.Measurement result is in Table 4 and Fig. 1.
Table 4 Indigo Naturalis micropowder and Indigo Naturalis activation micropowder qualification result
Utilizing XRD to detect, inspect out three kinds of inorganic matters from Indigo Naturalis, is respectively CaCO
3, Ca (OH)
2with SiO
2.Both diffraction maximums are basically identical, but the proportion of composing of three kinds of inorganic matters is variant.CaCO after Indigo Naturalis modification
3content 4.8%, the Ca (OH) that risen
2content 5.1%, the SiO that declined
2changes of contents is little.Its reason of changes is that 95% ethanol easily has good wettability, can spread over Indigo Naturalis powder surface, makes it in process of lapping, and Indigo Naturalis surface is wetting state, is contacting or is drying in the process of dispelling ethanol subsequently, Ca (OH) with air
2with airborne a small amount of CO
2react, generate CaCO
3, quality slightly increases.But significance does not occur the content and component proportion of inorganic matter changes, it not the main cause that Indigo Naturalis wettability strengthens.
(6) in hydrophilic natural indigo decoction piece, the infrared spectrum of ethanol is identified
The spectroscopic pure KBr of drying is blank, prepares the sample of infrared analysis.Every middle KBr content is 60mg, and sample size is about 0.8mg, and with FTIR-650 Fourier infrared spectrum measurement instrument, spectrogram is in Table 5 and Fig. 2～5:
Table 5
From infrared spectrogram, can clearly see, Indigo Naturalis micropowder and Indigo Naturalis raw material are basically identical, and all groups can coincide substantially, and significant chemical change does not occur the micronization of Indigo Naturalis.But hydrophilic Indigo Naturalis is 3500cm in wave number
-1near hydroxyl peak intensity significantly strengthens compared with Indigo Naturalis micropowder decoction pieces, illustrates in Indigo Naturalis lyophilic powder decoction pieces and has newborn great amount of hydroxy group (-OH) to exist; At 1460cm
-1peak intensity also strengthens, and illustrates and in Indigo Naturalis lyophilic powder decoction pieces, has newborn methyl (-CH
3), methylene (-CH
2-) exist; This is the key evidence that in Indigo Naturalis lyophilic powder decoction pieces, ethanol exists.
(7) mensuration of ethanol content in hydrophilic decoction pieces
The preparation of reference substance solution: get chromatographic grade dehydrated alcohol 0.2636g, be transferred to 50ml volumetric flask, add DMF to scale, shake up, ultrasonic 20 minutes, be cooled to room temperature, obtain the reference substance solution that concentration is 5.272mg/ml.
The preparation of need testing solution: get the test sample 0.5g of hydrophilic natural indigo decoction piece, to 25ml volumetric flask, add DMF to scale, shake up, ultrasonic 20 minutes, be cooled to room temperature, cross 0.45 μ m microporous filter membrane, obtain.
The preparation of negative solution: get the test sample 0.5g of common natural indigo decoction piece, to 25ml volumetric flask, add DMF to scale, shake up, ultrasonic 20 minutes, be cooled to room temperature, cross 0.45 μ m microporous filter membrane, obtain.
Chromatographic condition: Agilent7890A GC System, Agilent Chemstation work station; Knitting wool tubing string: HP-FFAP30m*0.25mm0.25 μ m film; Column oven: 50 ℃ of initial temperatures, retention time 2min, 15 ℃/min temperature programming to 180 ℃, retention time 10min; 240 ℃ of fid detector temperature, 180 ℃ of injector temperatures; Hydrogen flow rate: 40ml/min, nitrogen flow rate 30ml/min, air velocity 300ml/min; Sample size: reference substance, need testing solution are 2 μ L.
Chromatograph specificity is investigated:
From Fig. 6-8, the retention time of dehydrated alcohol is 4.08min, and the method specificity is good, and common natural indigo decoction piece does not comprise ethanol, and the method can be used as the method for measuring of Indigo Naturalis ethanol content.
Result is measured: adopt the content of ethanol in external standard method hydrophilic natural indigo decoction piece, recording hydrophilic natural indigo decoction piece (before dry) ethanol content is 4.68%, and hydrophilic natural indigo decoction piece (after dry) ethanol content is 0.79%.
Because novel natural indigo decoction piece product need be dried rear packing, difference between considering batch, is decided to be 0.3%-5.0% by the ethanol content scope in finished product.
(9) mensuration of critical relative humidity
By preceding method, drying under reduced pressure to Indigo Naturalis routine and the ultra-micro powder of constant weight put into the flat weighing botle (the about 3mm of powder thickness) that is dried to constant weight, accurately weigh, then be placed in the exsiccator that fills respectively 7 kinds of listed different salt supersaturated solutions of following table, in constant incubator, preserve 7 days for 25 ℃, regularly weigh the moisture absorption percentage rate of various powder while calculating moisture equilibrium at dry side.
The saturated aqueous solution of the different salt of table 6 is at the relative humidity of 25 ℃
| Saturated solution | 54%H 2SO 4 | 48%H 2SO 4 | 44%H 2SO 4 | NaBr | NaCl | KCl | KNO 3 |
| Relative humidity (%) | 30.5 | 41.2 | 49.8 | 57.7 | 75.4 | 84.4 | 92.9 |
Draw the moisture equilibrium at dry side curve of Indigo Naturalis micropowder and hydrophilic natural indigo decoction piece.Take relative humidity as abscissa (RH%), moisture absorption percentage rate is vertical coordinate (%) mapping, application OriginPro8.5 software is made the tangent line at two curve two ends, abscissa corresponding during two points of intersection of tangents is critical relative humidity, and the critical relative humidity of Indigo Naturalis micropowder decoction pieces and Indigo Naturalis hydrophilic decoction pieces is respectively 63.43% and 61.94%.After hydrophilically modified, critical relative humidity slightly reduces.
Embodiment 3 preparation technologies' of the present invention screening
The hydrophilic relation of contact angle and material:
When drop is freely during the space in the impact that do not stress, because the existence of interfacial tension is spherical shape.But when drop contacts with surface, its net shape depends on the cohesiveness of drop inside and the relative size of the adhesion between drop and solid.When a drop is placed on surface, drop can automatically be sprawled and come at the surface of solids, or to become the drop of certain contact angle to exist with the surface of solids.
Suppose that the interfacial tension that power between different interfaces can be used as being used in interface direction represents,, when drop is on surface during in equilbrium position, these interfacial tensions component sum in the horizontal direction should equal zero,
γ
S/A=γ
S/L+γ
L/Acosθ
In formula, γ S/A, γ L/A, γ S/L are respectively solid-gas, liquid-gas and solid-liquid interface tension force; θ is the angle of the tangent line folded (comprising liquid) of interface between liquid and solid and liquid surface, is called contact angle (contact angle), and θ is between 0 °-180 °.Contact angle is the key criteria of reacting substance and liquid wettability relation, and θ=90 ° can be used as moistening and non-wetted boundary, wettable in the time of θ <90 °, nonwetting in the time of θ >90 °.As from the foregoing, contact angle is the hydrophilic important indicator of reflected appraisal medicine.The present invention be take contact angle and Indigo Naturalis method of modifying is investigated as index.
1, the screening test of activator
Choose in pharmaceuticals industry widely used alcohol reagent and surfactant as Indigo Naturalis activator, such material contains lipophilic group alkyl and hydrophilic radical, this well meets activation Indigo Naturalis material property, simultaneously, the water of usining contrasts as modified active, by investigating contact angle, be evaluation index, screening modifier kind.
(1) experiment medical material and reagent
Indigo Naturalis granule, the permanent source of Sichuan Pharmaceutical provides; Methanol, ethanol, propanol, n-butyl alcohol, ethylene glycol, glycerol etc., be more than analytical pure, is purchased from Sichuan Ke Long chemical reagent company limited.
(2) experimental apparatus
Pine high mountain board vibromill; OCA20 video optics contact angle instrument (German Dataphysics company); Sartorius electronic balance (Beijing Sai Duolisi instrument system company limited) etc.
(3) preparation of different activator Indigo Naturalis activation micropowders
Alcohols material is selected monohydric alcohol: methanol, 95% ethanol, propanol, n-butyl alcohol; Dihydroxylic alcohols: ethylene glycol; Trihydroxylic alcohol: glycerol.Surfactant-based selection anion surfactant: sodium lauryl sulphate (sodium lauryl sulfate); Cationic surfactant: bromo geramine (benzalkonium bromide); Non-ionic surface active agent: Tween 80.
Before Indigo Naturalis is pulverized, moisture control is in 8%.In crushing process, in Indigo Naturalis, add the modifier of 19% above-mentioned Indigo Naturalis crushing quantity to grind.Technological parameter: charge ratio of media 80%, column rustless steel medium, amplitude 4mm, time 23min, operating temperature-20 ℃.Prepare finished product and be placed in sealing bag and deposit in 25 ℃ of exsiccators, standby.
(4) the contact angle evaluation of different activator hydrophilic Indigo Naturaliss under different baking temperatures
Adopt video optics contact angle instrument (OCA20 video optics contact angle instrument, Germany Dataphysics company) measure Indigo Naturalis activation micropowder at not dry, 40 ℃, 60 ℃, 80 ℃, 100 ℃ dried contact angles, with this, judge the wettability of powder surface.Utilize the full pressed powder of single punch tablet machine, above-mentioned powder body is pressed into respectively to heavy 0.3g, the slice, thin piece that diameter is 12mm, hardness requirement is not less than 60N.Tablet hardness is measured with YD-20 tablet hardness instrument (Tianda Tianfa Technology Co., Ltd.).
During mensuration, test fluid is selected distilled water, and each test fluid volume is 60 μ L, and speed is 0.5 μ L/s.Fixedly the distance on needle point lower end and slice, thin piece top is 2.0mm.During mensuration, select the lower surface of tablet to do test surfaces (upper surface is not very flat) as far as possible.The water is just on the boil begins and slice, thin piece upper surface Contact for record, and the picture that shooting function captures, calculates initial (initial CA), until water droplet, when sheet sub-surface forms more fixing contact angle, then record, is equilibrium contact angle (balance CA), every kind of powder body is at least surveyed 3 times, averages.The results are shown in Table 7 and Fig. 9.
Table 7: the contact angle of different activator activation Indigo Naturaliss changes
Known by the above results, utilize different modified active agent to activate Indigo Naturalis, can improve in various degree the poor characteristic of Indigo Naturalis hydrophilic, illustrate and adopt a kind of solvent simultaneously with lipophilic group and hydrophilic group can activate Indigo Naturalis surface, impel it to have good hydrophilic, between the lipophilic group (hydrophilic group) of this process (possibility) by modified active agent and Indigo Naturalis component molecules, interaction produces.
2, hydroxyl, the impact research of alkyl on Indigo Naturalis activation effect
Consider popularity, safety that solvent borne is used, and the feasibility of suitability for industrialized production, in conjunction with above-mentioned result of the test, select activation effect still good, the good ethanol of stability is further studied.Above-mentioned test knows, ethanol can be used as activator activation Indigo Naturalis, and this activation results is that in alkyl in ethanol molecule or hydroxyl and Indigo Naturalis, Related Component molecule interacts and the effect that produces in the presence of mechanical force.The research hydrophilic variation of Indigo Naturalis that has been which kind of group major effect on earth, for large Manufacturing science, reasonably select modifier most important.
(1) hydrophilic Indigo Naturalis wettability preliminary test
Ethanol is mixed with to not isocyatic ethanol water, measures the impact that ethanol changes the surface tension of water.Indigo Naturalis and activation Indigo Naturalis are scattered in respectively in water and 50% ethanol water, whether observe both Indigo Naturaliss dispersibles in two kinds of solution, then, the centrifugal 10min(4000r/min of Indigo Naturalis being scattered in water-alcohol solution), discard brown color supernatant, collecting precipitation, dries to constant weight for 50 ℃, redispersion, in water, is observed dispersion effect.The results are shown in Table 8.
Table 8 ethanol changes Indigo Naturalis-wettability
By table 8 result, can be found out, ethanol can improve the wettability of Indigo Naturalis in water under the effect of mechanical force.In experiment, after 50 ℃ of oven dry of hydrophilic Indigo Naturalis, still can be dispersed in water, between surperficial ethanol and Indigo Naturalis, have stronger adhesion.By interpretation, Indigo Naturalis powder and Indigo Naturalis micropowder can not be scattered in water, when both dispersions are entered in 50% ethanol water, particle surface contacts with ethanol molecule, and intermolecular force has increased particle wettability in alcoholic solution, and then is scattered in alcoholic solution, after oven dry, the volatilization of particle surface ethanol, does not activate Indigo Naturalis and can not be scattered in water, and the hydrophilic decoction pieces after activation can be scattered in water again.Based on this, there is following supposition particle to pulverize in activation process, utilize mechanical stress to activate particle surface, to change particle surface structure and physical arrangement, because inside particles breaks, interior can increase, under external force, ethanol activation rear portion ethanol enters in the space of Indigo Naturalis particle, another part is wrapped in around Indigo Naturalis particle, after oven dry, the ethanol molecule on surface is waved away, but the ethanol molecule in molecule gap may have compared with strong adhesion and be difficult to be pulled away with some interaction of molecules in Indigo Naturalis composition.Inventor thinks, 1. hydrophilic group-OH and the interactional result of Indigo Naturalis component molecules in ethanol.In the structure of the organic principle molecule in Indigo Naturalis, generally contain C-O bonding C-N part, the O that electronegativity is larger and N in molecule or the existence of intermolecular hydrogen bonding prerequisite is provided, meanwhile, have document also intramolecular hydrogen bond in Indigo Naturalis to be made to sufficient analysis.Under mechanical force, ethanol enters in Indigo Naturalis particle, and simultaneously intramolecular hydrogen bond is activated, and then forms alternately new hydrogen bond with the hydrophilic group-OH of ethanol, and still hydrophilic is good to make hydrophilic natural indigo decoction piece after drying.2. lipophilic group-CH in ethanol
2cH
3with the interactional result of Indigo Naturalis component molecules.At present, people generally believe in Indigo Naturalis except containing above-mentioned effective ingredient, also contain a large amount of Calx, still, have scholar to pass through scanning electron microscope, X-diffraction investigation is found, the inorganic constituents in Indigo Naturalis is mainly CaCO
3and SiO
2, and indigo be to depend on CaCO
3plane of crystal exists.This explanation Indigo Naturalis particle is that the organic molecules such as activated Calcium carbonate absorption is indigo, indirubin form, and these organic molecules have obvious lipotropy, show that they and shipwreck are in affine.The existing lipotropy alkyl-CH of ethanol
2cH
3there is again hydrophilic-OH, the lipophilic group of alkyl wherein in Indigo Naturalis carries out physical chemistry is combined, and forms unimolecule active layer, and its hydrophilic-OH is just exposed to particle periphery, good with regard to energy like this and hydrone interacts, and increases the hydrophilic of Indigo Naturalis particle.
(2) impact of hydroxyl quantity on Indigo Naturalis activation effect
Choose monohydric alcohol: 95% ethanol; Dihydroxylic alcohols: ethylene glycol; Trihydroxylic alcohol: glycerol contrasts as activator, usings water as with reference to activator.Described in the preparation of activation Indigo Naturalis micropowder and assay method photograph are front.Containing the impact of different hydroxyl alcohols on the contact angle of Indigo Naturalis modification micropowder, the results are shown in Table 9.
Table 9 is containing the impact of different hydroxyl alcohols on the contact angle of Indigo Naturalis modification micropowder
By experimental result, found out, on each temperature spot, under the identical condition of alkyl, hydroxyl is more, Indigo Naturalis modification micropowder no matter is initial or equilibrium contact angle is just less, this is because the more hydrophilic of hydroxyl are stronger, hydroxyl is polar group, water is had to large affinity, can attract hydrone, show that alcoholic extract hydroxyl group has certain contribution function to Indigo Naturalis micropowder wettability simultaneously, but ethylene glycol and glycerol is initial suitable with equilibrium contact angle numerical value, prompting, and the wettability of more Indigo Naturaliss of non-hydroxyl micropowder is just better, this may also have relation with alkyl quantity and the space conformation of alcohol apoplexy due to endogenous wind.
(3) impact of alkyl length on Indigo Naturalis activation effect in alcoholic solution
Choose monohydric alcohol: methanol, 95% ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol contrast as activator, using water as with reference to activator.Described in the preparation of activation Indigo Naturalis micropowder and assay method photograph are front.Containing the impact of different alkyl alcohols on the contact angle of Indigo Naturalis modification micropowder, the results are shown in Table 10.
Table 10 is containing the impact of different alkyl alcohols on the contact angle of Indigo Naturalis modification micropowder
By experimental result, found out, on each temperature spot, under the identical condition of hydroxyl, alkyl is longer, and Indigo Naturalis modification micropowder no matter is initial or equilibrium contact angle is just less, and this shows that alkyl has certain contribution function to Indigo Naturalis micropowder wettability.
In experiment, the wettability of each hydrophilic natural indigo decoction piece is different, also there is relation with the stability of activator, the stability of methanol, ethanol, propanol, n-butyl alcohol, ethylene glycol and glycerol strengthens successively, and ethylene glycol and glycerol are suitable, six boiling point also increases successively, particularly the effumability of methanol and ethanol causes both hydrophilic natural indigo decoction piece wettabilitys not as other alcohols, but the airtight placement of room temperature after two months, the hydrophilicity of propanol and n-butyl alcohol reduces, and approaches with methanol, ethanol.Comprehensive above-mentioned research, considers the factors such as safety, cost, selects ethanol to be advisable as modifier.
3, ethanol modified technique research
In conjunction with above-mentioned result of the test, consider the popularity of solvent use and the feasibility of industrialized great production, select ethanol as activator, Indigo Naturalis active artistic condition to be studied.
(1) single factor is investigated amount of alcohol added to the hydrophilic impact of Indigo Naturalis
Fixing milling time (23min), vibromill amplitude 4mm, charge ratio of media 80%, operating temperature-20 ℃, feed intake with Indigo Naturalis coarse powder, and material water ratio is controlled in 8%, investigates the impact of amount of alcohol added on Indigo Naturalis activation effect, the results are shown in Table 11.
The impact of table 11 amount of alcohol added on Indigo Naturalis Powder Contact Angle and particle size distribution
From result, the contact angle of hydrophilic natural indigo decoction piece reduces with the increase of amount of alcohol added, particle size distribution (D
0.9) increase, and the variation of contact angle and the obvious dependency of particle size distribution size nothing.Along with the increase of amount of alcohol, the alkyl in system and hydroxyl quantity increase, and have increased the combination chance of Indigo Naturalis particle and alkyl, finally make the contact angle of Indigo Naturalis modification micropowder constantly reduce.Along with adding of amount of alcohol, Ethanol Adsorption is at Indigo Naturalis particle surface, make the valence link power on the plane of disruption obtain saturated, agglomeration power between granule is shielded, the cohesiveness that suppresses granule, promote the crushibility of granule, but constantly increasing progressively of amount of alcohol makes to form multilayer molecular absorption in system, impels particle diameter to become gradually large.From above, know, during amount of alcohol added 17%, contact angle is minimum.
(2) impact of vibromill technique (amplitude) parameter on Indigo Naturalis modified effect
Get dry rear common decoction pieces 400g in vibromill, add 95% alcoholic solution mixed grinding of 19% Indigo Naturalis crushing quantity to pulverize 23min, vibromill charge ratio of media 80%, column rustless steel medium; Investigate amplitude (4mm, 5mm, 6mm) to the hydrophilic impact of Indigo Naturalis.Take out rear 50 ℃ of forced air drying 20min, to without alcohol taste, seal and preserve, measure its contact angle.
The impact of table 12 amplitude on wettability
As can be seen from the above table, amplitude has certain influence to experimental result, and along with the increase of amplitude, contact angle has the trend of increase.Therefore, the preferred best amplitude of the present invention is 4mm.
(3) single factor is investigated the vibro-grinding time
Fixedly activator addition is 17%, vibromill amplitude 4mm, and charge ratio of media 80%, operating temperature-20 ℃, feed intake with Indigo Naturalis coarse powder, and material water ratio is controlled at 8% left and right, investigates the impact of milling time on Indigo Naturalis activation effect, the results are shown in following table.
The impact of table 13 milling time on Indigo Naturalis Powder Contact Angle and particle size distribution
From experimental result, the equilibrium contact angle of hydrophilic natural indigo decoction piece and particle size distribution (D
0.9) with the increase of milling time without significant change, initial contact angle has the trend reducing, and shows that milling time has certain dependency to initial contact angle.Milling time increases the action time that extends ethanol molecule and Indigo Naturalis particle, impel mechanical energy to be converted into physical chemistry bond energy, the combination of ethanol molecule and Indigo Naturalis particle is more firm, dissociate-OH trends towards aligning, when Indigo Naturalis particle is just contacted with water, more easily by water liquid, sprawled.
(3) uniform Design optimizing factors level
Adopt U
5(5
2) uniform designs table, arrange X1(ethanol consumption) and X2(milling time), every factor arranges 5 levels, and specific design is as table 14, with equilibrium contact angle and particle size distribution D
0.9for evaluation index, screening optimum process condition, experimental result is in Table 15.
Table 14U
5(5
2) uniform designs table
Table 15 level is replaced and result of the test
Adopt SPSS17.0 statistical software to analyze result of the test, the general introduction of Model Summary(model) show and be selected into X
1(ethanol consumption), proofreaies and correct coefficient of determination R
2=0.904, ANOVA(variance analysis) show F=28.173, P=0.013, successive Regression equation has statistical significance.
Table 16 variable analysis
| Variable | Partial regression coefficient t | P |
| (constant) | 20.163 | 0.000 |
| X 1 | -5.301 | 0.013 |
| X 2 | -2.396 | 0.139 |
By upper table, known X
1should bring equation into, X
2should reject, obtaining regression equation is Y
1=54.513-X
1* 2.443; X
2=3, the approximate evaluation of optimum point is:
X
1=19，X
2=23
Therefore the approximate evaluation of optimal case is: activator level is 19%, grind 23min.
Embodiment 4 is dried or the impact of storage temperature on hydrophilic Indigo Naturalis of the present invention
(1) drying time determining the impact of Residual ethanol in hydrophilic decoction pieces and drying time
The hydrophilic Indigo Naturalis of getting embodiment 1 preparation is some, sealing is stored in sealing bag, get and be laid in right amount dry placement under 50 ℃ of conditions in square plate, respectively at the 10th, 20,30,40min sampling, according to the lower test sample preparation method of (7) item, prepare test sample, parallel 3 parts, measure the wherein content of alcohol residue, experimental result sees the following form.
The assay result of table 17 different time points Residual ethanol
As can be seen from the above table, after dry 20min, ethanol content changes not quite, therefore, determines that be 20min drying time.Now, in 1g hydrophilic decoction pieces, the average content of ethanol is 6.66mg, and mean concentration is 0.67 ± 0.02%.
(2) heat treated is on the hydrophilic impact of hydrophilic decoction pieces (preliminarily stabilised Journal of Sex Research)
The about 3g of hydrophilic decoction pieces that takes embodiment 1 preparation, is laid in weighing botle, parallelly takes 27 parts, in the baking oven of 40,60,80 ℃, respectively place 9 parts, open wide to place, respectively at 1,2,3h respectively takes out 3 parts, measure its contact angle and alcohol residue, experimental result sees the following form.
The impact of table 18 heating on contact angle and ethanol content
As can be seen from the above table, different heating-up temperatures is different on the impact of hydrophilic decoction pieces stability, and heat treatment temperature is higher, affects more obvious.After 40 ℃ of heat treated 3h, contact angle and the alcohol residue of hydrophilic decoction pieces slightly change, but change not quite, still have good wettability; 60 ℃ with 80 ℃ of heat treated after, initial contact angle and equilibrium contact angle obviously raise, Residual ethanol obviously reduces, but still has certain wettability.As can be seen here, hydrophilic natural indigo decoction piece prepared by the present invention all can keep certain wettability at 80 ℃ with interior storage 3h, especially better at wettability below 40 ℃.
The present embodiment has been investigated and take the ball mill that planetary ball mill is representative and whether can prepare hydrophilic natural indigo decoction piece.
Selecting ND8 type adjustable swing-type planetary ball mill (Nanda Tianzun Electronics Co., Ltd., Nanjing) is milling apparatus, dried natural indigo decoction piece is dropped in Achates tank, add 95% ethanol that accounts for Indigo Naturalis weight 19%, in swing type planetary ball mill, carry out solid-liquid grinding.Because revolution is the key factor that determines grinding efficiency, therefore, the present invention has mainly investigated the impact of revolution on experimental result.
Setting ball mill running parameter is respectively: globe mill medium filling rate is 30%, ratio of grinding media to material 12:1, and milling time is 90min, adopts single factor method to investigate the impact of rotating speed (100,200,300r/min) on Indigo Naturalis wettability.Ground decoction pieces is put into 40 ℃ of dry 20min of air dry oven, carries out contact angle determination, and experimental result sees the following form.
The impact of table 19 revolution on wettability
As can be seen from the above table, adopt planetary ball mill function to improve the surface wettability of Indigo Naturalis, its contact angle is reduced, and hydrophilically modified effect is more obvious along with the quickening of revolution.This frequency of impact and number of shocks that may can improve between globe mill medium and material with raising rotating speed is relevant.
By following test example, beneficial effect of the present invention is described
The acute toxicity test of test example 1 Indigo Naturalis lyophilic powder decoction pieces
With traditional natural indigo decoction piece comparison, be prepared into after lyophilic powder decoction pieces, hydrophilic strengthens, also introduced a small amount of ethanol simultaneously, for guaranteeing the safety of clinical use, according to < < Chinese medicine, natural drug studies on acute toxicity technological guidance principle > >, Indigo Naturalis lyophilic powder decoction pieces has been carried out to studies on acute toxicity.
Tested medicine: Indigo Naturalis lyophilic powder decoction pieces (self-control).KM mice, regular grade, body weight 18-22g, male and female half and half, by Chengdu, Da Shuo bio tech ltd provides.
Sample preparation: take a certain amount of modification Indigo Naturalis powder as test sample, be made into suspension with normal saline, concentration is 0.4g/mL, and jolting is evenly used before use.
Prerun test: get KM mice, body weight 18-22g, male and female half and half, are divided into five groups at random, i.e. medicine 1 group of (0.2ml/20g), medicine 2 groups of (0.4ml/20g), medicine 3 groups of (0.6ml/20g), 4 groups of medicines (0.8ml/20g) and blank group (normal saline group) (in Table 1).Before administration, fasting is 12 hours, can't help water, oral administration gavage administration, and after administration, the mental status of 7 days mices of Continuous Observation, diet situation, poisoning time etc., perform an autopsy on sb． to mice after test.Because administration volume is very large, while being the maximum administration capacity of mice, there is not death in mice, and also without obviously toxic reaction, prompting this product is difficult to measure LD
50therefore, carry out maximum dosage-feeding determination test.Grouping and administration situation are in Table 20.
Table 20 grouping and administration situation
Maximum dosage-feeding test: get KM mice, female half and half, body weight 18～22g, is divided into two groups at random.Fasting is 12 hours before administration, can't help water, minute 3 oral administration gavage administrations in 24 hours, i.e. 34.29g/kg body weight, blank group of normal saline that gives same dosage with method, Continuous Observation 7 days.Itemized record mice behavioral activity, state, diet, defecation and hair color, secretions etc., dissect inspection to mice after test.
Prerun result of the test: mice, in gavaging 7 days of medicine, has of short duration discomfort on the 1st day, movable minimizing, stool color is blue black color, within the 2nd day, recover normal, freely, feed, drinking-water are normally in mice activity, stool be wet particle shape, for dark brown, during have no poisoning symptom and death.Perusal finding after dissecting: thoracic cavity, abdominal cavity no abnormality seen liquid, intestinal tube has no flatulence, the important organs such as the heart, liver, spleen, lung, kidney have no color, paramophia, there is no petechia or other pathological change, gastric mucosa color is ruddy, without petechia or ulcer, with blank group zero difference, postmortem is without extremely.
Maximum dosage-feeding result of the test: mice in gavaging 7 days of medicine, the 1st, 2 days movable minimizings, food, amount of drinking water reduce relatively, within the 3rd day, recover normal; After mice administration, the stool color of the 1st day is blue black color, within the 2nd day, recovers normal; Outward appearance sign no abnormality seen, freely, feed, drinking-water, feces are all normal in activity, and fur is bright and clean, mouth, nose, eye and Anal cleaning be without secretions, Continuous Observation 7 days, and 40 mices all survive, body weight increases, and changes no significant difference (P > 0.05, in Table 16) between group; Have no during this time poisoning symptom and death; Perusal finding after dissecting: thoracic cavity, abdominal cavity no abnormality seen liquid, intestinal tube has no flatulence, the important organs such as the heart, liver, spleen, lung, kidney have no color, paramophia, there is no petechia or other pathological change, the heart, liver, spleen, lung, renal index no significant difference (P > 0.05 between group, in Table 21,22), gastric mucosa color is ruddy, and without petechia or ulcer, postmortem is without extremely.
Body weight change situation after the administration of table 21 mice maximum
Note: with the comparison of blank group, after administration 7 days, 1. represent P > 0.05
The heart, liver, spleen, lung, renal index situation of change after the administration of table 22 mice maximum
Note: with the comparison of blank group, after administration 7 days, 1. represent P > 0.05
This liquor strength is 0.4g/ml, mice administration every day 2.4ml, and mice is taken medicine and be equivalent to Indigo Naturalis 0.96g/20g every day, and its tolerance multiple is 342.9 times of people, so, can think this medicine avirulence.
In sum, hydrophilic Indigo Naturalis of the present invention, has significantly reduced the contact angle of Indigo Naturalis, can effectively improve the dispersibility of Indigo Naturalis in water, overcome common Indigo Naturalis and floated on liquid level, be difficult to disperse to enter the problem in water, the patient that is more convenient for uses, improved the utilization rate of medical material, and safety is good; The preparation method of hydrophilic Indigo Naturalis of the present invention is easy, with low cost, is conducive to large-scale production, has a good application prospect.
Claims (10)
1. a hydrophilic Indigo Naturalis, is characterized in that: described hydrophilic Indigo Naturalis contains activator more than 0.3%w/w; In described activator, contain lipophilic group alkyl and hydrophilic radical simultaneously; Preferably, the activator that described hydrophilic Indigo Naturalis contains 0.3%-5.0%w/w.
2. hydrophilic Indigo Naturalis according to claim 1, is characterized in that: described activator is that alcohols solvent is or/and surfactant.
3. hydrophilic Indigo Naturalis according to claim 2, it is characterized in that: described alcohols solvent is the alcohols solvent containing C1-10 straight or branched, be preferably the aqueous solvent of methanol, ethanol, dehydrated alcohol, propanol, n-butyl alcohol, ethylene glycol, glycerol, above-mentioned alcohols solvent or the mixture of multiple alcohols, more preferably 95%v/v ethanol; Described surfactant is anion surfactant, cationic surfactant, zwitterionic surfactant or non-ionic surface active agent, is preferably sodium lauryl sulphate, benzalkonium bromide, tween, span, quaternary ammonium compound, lecithin or aminoacid.
4. the preparation method of hydrophilic Indigo Naturalis described in claim 1-3 any one, is characterized in that: get Indigo Naturalis, in crushing process, pulverize with activator simultaneously, remove residue activator, obtain hydrophilic natural indigo decoction piece.
5. preparation method according to claim 4, its feature is greater than: the addition of described activator is the more than 3% of Indigo Naturalis weight, is preferably 10～19%.
6. according to the preparation method described in claim 4 or 5, it is characterized in that: described pulverizing adopts vibromill, ball mill or rod formula grinder to carry out.
7. preparation method according to claim 6, is characterized in that: the time that adopts vibromill to pulverize is 1-60min; Be preferably 20-40min; 23min more preferably.
8. according to the preparation method described in claim 6 or 7, it is characterized in that: in vibromill crushing process, charge ratio of media 30-95%, medium material is rustless steel, special stainless steel or pottery, shape of medium is cylindrical, spherical; Amplitude 2-6mm; Operating temperature-160～80 ℃; Preferably, charge ratio of media is 80%, column rustless steel medium, amplitude 4mm, operating temperature-20 ℃.
9. preparation method according to claim 6, is characterized in that: in ball mill crushing process, rotating speed is 100～300 turn/min, and charge ratio of media is 30～50%, ratio of grinding media to material 10～14:1, and milling time is 80～100min; Preferably, rotating speed is 300 turn/min, and charge ratio of media is 30%, ratio of grinding media to material 12:1, and milling time is 90min.
10. according to the preparation method described in claim 4～9 any one, it is characterized in that: remove residue activator after, by gained solid at 50 ℃ with inner drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310528983.1A CN103536633B (en) | 2012-10-31 | 2013-10-30 | A kind of hydrophily indigo naturalis and preparation method thereof |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210426313.4 | 2012-10-31 | ||
| CN201210426313 | 2012-10-31 | ||
| CN2012104263134 | 2012-10-31 | ||
| CN201310528983.1A CN103536633B (en) | 2012-10-31 | 2013-10-30 | A kind of hydrophily indigo naturalis and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103536633A true CN103536633A (en) | 2014-01-29 |
| CN103536633B CN103536633B (en) | 2016-05-18 |
Family
ID=49960747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310528983.1A Active CN103536633B (en) | 2012-10-31 | 2013-10-30 | A kind of hydrophily indigo naturalis and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103536633B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111493198A (en) * | 2020-05-18 | 2020-08-07 | 哈尔滨梵境园生物科技有限公司 | Preparation method of functional plant pressed candy slices |
| CN113730588A (en) * | 2020-09-30 | 2021-12-03 | 成都中医药大学 | Hydrophilic natural indigo and preparation method thereof |
| CN116036293A (en) * | 2022-12-02 | 2023-05-02 | 成都中医药大学 | Natural indigo dry suspension and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1615924A (en) * | 2003-11-13 | 2005-05-18 | 四川江油恒源药业集团有限公司 | Improved producing method for processing natural indigo |
| CN102018736A (en) * | 2010-11-19 | 2011-04-20 | 成都中医药大学 | Natural indigo decoction piece and preparation method thereof |
-
2013
- 2013-10-30 CN CN201310528983.1A patent/CN103536633B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1615924A (en) * | 2003-11-13 | 2005-05-18 | 四川江油恒源药业集团有限公司 | Improved producing method for processing natural indigo |
| CN102018736A (en) * | 2010-11-19 | 2011-04-20 | 成都中医药大学 | Natural indigo decoction piece and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周海云等: "青黛脂溶性提取物固体分散体制备及溶解性研究", 《时珍国医国药》, vol. 18, no. 11, 30 November 2007 (2007-11-30), pages 2756 - 2758 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111493198A (en) * | 2020-05-18 | 2020-08-07 | 哈尔滨梵境园生物科技有限公司 | Preparation method of functional plant pressed candy slices |
| CN113730588A (en) * | 2020-09-30 | 2021-12-03 | 成都中医药大学 | Hydrophilic natural indigo and preparation method thereof |
| CN113730588B (en) * | 2020-09-30 | 2022-11-29 | 成都中医药大学 | Hydrophilic natural indigo and preparation method thereof |
| CN116036293A (en) * | 2022-12-02 | 2023-05-02 | 成都中医药大学 | Natural indigo dry suspension and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103536633B (en) | 2016-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103536633A (en) | Hydrophilic natural indigo and preparation method thereof | |
| CN105859903A (en) | Radix glehniae polysaccharide and preparation method and application thereof | |
| CN106248842A (en) | A kind of content assaying method of four seasons SANHUANG PIAN | |
| CN1739598A (en) | Chinese medicine injection for treating cancer and its prepn process and quality control method | |
| CN100418562C (en) | Medicinal composition, its preparing method and quality controlling means | |
| CN105106816B (en) | Protect the traditional Chinese medicine health care product preparation and preparation method thereof of chemical damage | |
| CN110579545A (en) | Quality detection method of traditional Chinese medicine composition for clearing heat and ventilating lung | |
| CN104922564B (en) | A kind of preparation method for treating medicine pill lungy | |
| CN105521363A (en) | Preparation method and quality control method of traditional Chinese medicine capsule for treating weakness of spleen and stomach | |
| Yao et al. | The absorption characteristics of nonvolatile components in a water extraction from Amomi fructus as determined by in situ single-pass intestinal perfusion and high-performance liquid chromatography | |
| CN102145089A (en) | Traditional Chinese medicine for treating heart failure | |
| CN111529586A (en) | A concentrated granule for preventing infection of novel coronavirus and its preparation method | |
| CN103550398A (en) | Composition for relieving fatigue as well as preparation method and medical application thereof | |
| CN106928376B (en) | The separation method of skunk bush polysaccharide and its application | |
| CN102293957B (en) | Chinese medicinal granules for treating related skin disease such as blood heat yang floating disease and preparation method thereof | |
| CN102049012B (en) | Traditional Chinese medicine composition for treating sexual precocity of children and preparation and quality detection method thereof | |
| CN109010220A (en) | A kind of cosmetic composition and preparation method thereof | |
| CN108338977A (en) | Eukaryotic cell membrane cladding bionic nano grain of anti-rotavirus infection and preparation method thereof | |
| CN107582639A (en) | A kind of vinegar corydalis tuber granule and preparation method thereof | |
| CN102949421A (en) | In-vitro antitumor effect of nanocrystallized ginseng | |
| CN103349737B (en) | Traditional Chinese medicine composite for treating headache and preparation method of traditional Chinese medicine composite | |
| CN110301641A (en) | A kind of health food of auxiliary protection stomach lining | |
| CN112137104A (en) | Composition with physical fatigue relieving function and preparation method thereof | |
| CN110403994A (en) | Application of the baitouweng decoction alcohol extract in preparation treatment oesophagus cancer drug | |
| CN110256591A (en) | A kind of Chinese caterpillar fungus polysaccharide extract and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160203 Address after: 610000 No. 2, West core road, hi tech Development Zone, Sichuan, Chengdu Applicant after: Sichuan HouDe Pharmaceutical Technology Co., Ltd. Address before: 610041 No. 29 Tian Xiao street, Chengdu, Sichuan, Wuhou District Applicant before: Chengdu Keer Medical Technology Co., Ltd. Applicant before: Sichuan HouDe Pharmaceutical Technology Co., Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200529 Address after: 625000 qianqianba formation, Qingjiang village, Siyan Township, Lushan County, Chengdu City, Sichuan Province Patentee after: YAAN XUNKANG MEDICINE Co.,Ltd. Address before: 610000 No. 2, West core road, hi tech Development Zone, Sichuan, Chengdu Patentee before: SICHUAN HOUDE PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right |