CN1887270A - Nanometer berberine hydrochloride emulsion and its prepn process - Google Patents
Nanometer berberine hydrochloride emulsion and its prepn process Download PDFInfo
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Abstract
The present invention discloses one kind of nanometer berberine hydrochloride emulsion. The nanometer berberine hydrochloride emulsion consists of berberine hydrochloride 0.1-2 wt%, surfactant 20-40 wt%, co-surfactant 10-20 wt%, solvent 1-10 wt%, oil phase 5-30 wt%, sweetener 1-5 wt% and distilled water 27.5-70 wt%. The nanometer berberine hydrochloride emulsion has raised berberine hydrochloride dissolubility, raised bioavailability, lowered toxic side effect, simple preparation process and low production cost.
Description
Technical field
The invention belongs to field of medicaments, relate to that a kind of medicine for the treatment of digestive system, cardiovascular system and kinds of tumors disease---the novel form of berberine hydrochloride is specifically related to a kind of nanometer berberine hydrochloride emulsion medicine and preparation method thereof.
Background technology
Berberine (be commonly called as and be berberine Berberine) is a kind of quaternary ammonium isoquinoline alkaloid that extracts from plant roots and stems such as hair castor section Rhizoma Coptidis.It has had the history in more than 3,000 year in China as digestive system disease, mainly treats enteritis.Modern study confirms that berberine can be widely used in various cardiovascular systeies, also kinds of tumors is had fabulous curative effect simultaneously.Because not dissolving in water of berberine, main preparation is various tablets of berberine and capsule on the domestic and international market.These conventional formulation, because liver is to the first pass effect of medicine, reason such as dissolubility is low in water, oral bioavailability lower (generally about 10%), patient's medication number of times is frequent, and toleration is poor.
Summary of the invention
Purpose of the present invention overcomes shortcomings and deficiencies of the prior art exactly, a kind of nanometer berberine hydrochloride emulsion preparation is proposed, this nano-emulsion preparation has improved the dissolubility of berberine hydrochloride, overcomes the extremely low shortcoming of its bioavailability in vivo, reduces its toxic and side effects.
Realize that foregoing invention purpose technical scheme is a kind of nanometer berberine hydrochloride emulsion preparation, comprise the berberine hydrochloride of following component: 0.1%-2%, the solvent of 1%-10%, the surfactant of 20%-40%, the cosurfactant of 10%-20%, the oil phase of 5%-30%, the sweeting agent of 1%-5%, the distilled water of 27.5%-70% is formed.
Described surfactant be in Tween-60, triglyceride, tween 80, the polyoxyethylene hydrogen flower Oleum Ricini any;
Described cosurfactant is any in Arlacel-80 and the sorbester p18;
Described oil is any in edible soybean oil, medicinal liquid paraffin, edible salad oil, Oleum Ricini, isopropyl myristate, the ethyl oleate;
Described solvent is any in dehydrated alcohol, n-butyl alcohol, glycerol, the 1,3 butylene glycol;
Described sweeting agent is sucrose or mannitol;
Described surfactant effective dose is Tween-60: 20-30%, triglyceride: 25-35%, tween 80: 20-40%, RH-40:20-30%;
Described kind of cosurfactant effective dose is Arlacel-80,10-20% and sorbester p18: 10-15%
Described oil phase effective dose is edible soybean oil: 10-30%, medicinal liquid paraffin: 10-30%, edible salad oil: 15-30%, Oleum Ricini: 15-30%, isopropyl myristate (IPM): 10-30%, ethyl oleate: 10-35%;
Described solvent effective dose is: dehydrated alcohol: 1-10%, n-butyl alcohol: 1-10%, glycerol: 1-10%, 1,3 butylene glycol: 1-10%;
The effective dose of described sweeting agent is: sucrose: 1-10% and mannitol: 1-10%.
Another object of the present invention provides a kind of preparation method of nanometer berberine hydrochloride emulsion preparation, specifically comprises the following steps:
1) it is standby to take by weighing berberine hydrochloride, solvent, surfactant, cosurfactant, oil phase, sweeting agent, distilled water by prescription;
2) with the surfactant and the berberine hydrochloride mixing of described amount, and be that 100～300r/m constant temperature blender with magnetic force stirs at rotating speed, temperature allows berberine hydrochloride be partly dissolved under 60～80 ℃ earlier;
3) cosurfactant and the solvent that adds described amount again dissolves fully by berberine hydrochloride, obtains clear solutions;
4) add the oil phase of described amount again, 80 ℃ of waters bath with thermostatic control, and be that 100～300r/m constant temperature blender with magnetic force stirs at rotating speed, adding distilled water, obtain clear solutions;
5) add at last the sweeting agent and the distilled water of described amount again, mixing obtains the solution of clear, promptly gets product of the present invention.
A kind of nano-emulsion preparation that contains berberine hydrochloride of the present invention can be made into dosage forms such as capsule, soft capsule, oral liquid, also can further be diluted to the nano-emulsion of stable any concentration with the moisture of arbitrary proportion, and make various corresponding dosage forms.
The nano-emulsion that the present invention adopts is made up of oil, water, surfactant, cosurfactant and solvent 5 parts, is that the emulsion droplet of a kind of particle diameter between 10～100nm is dispersed in the isotropic thermodynamically stable dispersion system of colloid that forms in the another kind of liquid.There are water and oil phase in the nanoemulsions simultaneously, have the fine solubility energy, can dissolve nonpolar hydrophobic drug, can dissolve polar hydrophilic medicament again.
The prescription design principle: as pharmaceutical carrier, nano-emulsion at first should meet the requirement of general pharmaceutical carrier, promptly nontoxic, non-stimulated, good medicine reason effect invariably, has excellent biological compatibility, the drug effect that does not influence principal agent and stability; Owing to the nano-emulsion self characteristics, it also has special requirement to each prescription composition in addition, medicine is had stronger solubilising power and can form the stabilized nano breast in a big way distinguish.The present invention follows this principle.
Surfactant is that microemulsion forms necessary material, and it mainly acts on is to reduce interfacial tension to form interfacial film, impels nano-emulsion to form.The selection of surfactant is decided by the characteristic and the application target of formed nano-emulsion.The HLB value can prepare the w/o type nano-emulsion at 4～7 surfactant, and the surfactant of HLB value in 8～18 can prepare O/W type nano-emulsion.The present invention adopts wherein surfactant Tweens, spans, the triglyceride of research the most frequently used high HLB value in reporting, polyoxyethylene hydrogen flower Oleum Ricini (RH-40).These surfactants, nontoxic non-stimulated, good biocompatibility has certain Nutrition, is the main adjuvant for preparing oral and injection nano-emulsion.
Because the formation of most of nano-emulsion all needs the participation of cosurfactant, its effect mainly is to assist surfactant to reduce interfacial tension between profit; Reduce the mutual repulsive force and the charge repulsion of surfactant, impel interfacial film to have good compliance and flowability, required interface bending energy when reducing nano-emulsion and generating makes nano-emulsion be easy to form; The HLB value of reconciliation statement surface-active agent.Cosurfactant commonly used has sorbester p17 and 60.The low chain alcohol that adopts among the present invention has the effect that strengthens cosurfactant as solvent.Owing to use cosurfactant, can allow in the nano-emulsion employed oil phase should and interfacial film upper surface active agent molecule between keep infiltration and get in touch, and be easy to and surfactant forms interfacial film, thereby be beneficial to the formation of nano-emulsion.
The present invention adopts oil phase commonly used to have salad oil, Oleum Glycines, Oleum Ricini, isopropyl myristate, ethyl oleate, medicinal liquid paraffin medium all edible, nontoxic non-stimulated, good biocompatibility has certain Nutrition, is the main adjuvant for preparing oral and injection nano-emulsion.
The present invention simultaneously also adds a spot of sweeting agent, can allow the present invention have good mouthfeel, is convenient to take.
The present invention compares with other prior art, has following beneficial effect:
1. the prepared nanoemulsion medicine of the present invention can solve the effect that conventional dosage forms has liver to cross on the one hand, increases medicine in the intravital absorption of flesh;
2. the dissolubility that solves berberine is low, increases medicine concentration in vivo, increases the curative effect of medicine, reduces the toxic and side effects of medicine;
3. can increase the berberine dispersibility, improve bioavailability of medicament;
4. nanoemulsion medicine can further add the moisture dilution of arbitrary proportion, forms the nano-emulsion of clear, and this nano-emulsion Thermodynamically stable can filtration sterilization, is easy to preparation and stores;
5. the prescription and the method simple possible that adopt of the present invention can be so that large-scale industrial production.
Description of drawings
Fig. 1 is blank nano-emulsion Electronic Speculum figure.
Fig. 2 is the transmission electron microscope photo (100,000 times) of nanometer berberine hydrochloride emulsion medicine of the present invention.
Fig. 3 is the particle size distribution figure of nanometer berberine hydrochloride emulsion preparation of the present invention.
The concrete test example and the specific embodiment that provide below in conjunction with the inventor further specify nanometer berberine hydrochloride emulsion preparation effect of the present invention.
The specific embodiment:
Test example 1
This experiment is measured by form, color, clarity, particle diameter and particle size distribution, physics and chemistry, safety to berberine mouth nanoemulsion medicine of the present invention, further specifies effect of drugs of the present invention.
1. test material
Used instrument is Xibei Univ. of Agricultural ﹠ Forest Science ﹠ Technology's laboratory and is existing instrument, and Kunming white mice body weight 18-22g is provided by The Fourth Military Medical University's animal center.
2. experimental technique and result
2.1 the form of nano-emulsion
The berberine nano-emulsion that takes a morsel is an amount of, behind 1 times of the dilute with water, drop on the copper mesh that is covered with supporting film, blot with filter paper behind the static 10min, drip 2% phosphotungstic acid (pH is 7.4) solution negative staining 3min on copper mesh again, naturally volatilize,, the results are shown in Figure 2 with transmission electron microscope observation and photographs.
The result shows that nano-emulsion all is spheroidal under Electronic Speculum, and inside is oil phase, sees Fig. 2 under Electronic Speculum, and picked at random is no less than 500 drops and measures particle diameter, gets nano-emulsion drop particle size range at 10-100nm, and mean diameter is about 56.8nm.
2.2 solution colour
The nanoemulsions for preparing is light yellow clarification, homogeneous, transparency liquid, according to " Chinese pharmacopoeia (version in 2005) the appendix IXA of II portion solution colour inspection technique is prepared yellowish green tone standard color solution.No. 1 color solution of nanoemulsions color and yellowish green tone is compared, must not be darker.
2.3 clarity
According to " checking that this product is a clear solutions under Chinese pharmacopoeia (version in 2005) the appendix IXB of the II portion clarity inspection technique.After the water for injection dilution, tangible nattier blue opalescence promptly appears.
2.4 particle diameter and particle size distribution
It is an amount of to get the berberine nano-emulsion, and with measuring with laser granulometry behind an amount of distilled water diluting, the particle diameter and the particle size distribution of nano-emulsion are seen Fig. 3.
Measurement result Fig. 3 shows, the berberine nano-emulsion mean diameter 56.8nm of Experiment Preparation.Particle less than 60nm accounts for 75%; Particle less than 70nm accounts for 90%, and the particle size distribution range of the nano-emulsion preparation that as seen makes is narrow, and size ratio is more even.
2.5. the physicochemical property of nano-emulsion
Viscosity (Rotary Viscosimeter), index of refraction (20oC, abbe's refractometer), electrical conductivity (conductivity meter), the Zeta potential (electromotive force microscopic electrophoresis instrument) of blank nano-emulsion and berberine nano-emulsion have been investigated.The results are shown in Table 1.
The physical and chemical property determining n=6 of table 1 nano-emulsion
| Sample | Viscosity/mm 2.s -1 | Index of refraction | Electrical conductivity/mS -1 | Zeta potential/mV |
| Blank nano-emulsion | 6.03±0.08 | 1.350±0.0041 | 328 | -5.25±0.06 |
| The berberine nano-emulsion | 6.32±0.07 | 1.360±0.0042 | 345 | -3.35±0.03 |
Experimental result shows that the adding of medicine increases the electrical conductivity of nano-emulsion, and Zeta potential significantly reduces, and viscosity and index of refraction do not have significant change (p＞0.05).
2.6 the preliminarily stabilised Journal of Sex Research of berberine nano-emulsion
With berberine raw material and berberine nano-emulsion (sealing by fusing is in the peace bottle) respectively at high temperature (40,60 ℃), carry out influence factor's experiment under low temperature (4 ℃) and illumination (4500 ± 1500) the lx environment, in 5, the 10d sampling, outward appearance and content to berberine raw material and the plain nano-emulsion of berberine are measured, and the results are shown in Table 3.Show that berberine is more stable under solid state, be subjected to temperature, humidity, illumination effect less; The berberine nano-emulsion phenomenon that layering, flocculation or medicine are separated out all do not occur under above-mentioned each condition, can think that nano-emulsion character is more stable; But nano-emulsion Chinese medicine content obviously descends under high temperature, illumination condition, illustrates that berberine is subjected to temperature and illumination effect bigger under liquid condition, and is comparatively stable under room temperature or cryogenic conditions, therefore can preserve under room temperature lucifuge condition.
Table 2 stability experiment is n=5 as a result
| Sample | Time | Content | ||||
| Berberine raw material berberine nano-emulsion | /d 0 5 10 0 5 | Relative humidity 92.5% 99.2 ± 1.5 98.2 ± 2.3 98.8 ± 1.1 100.3 ± 1.2 84.8 ± 1.2 | 60℃ 99.2±1.5 100.2±1.1 98.8±0.9 100.3±1.1 98.0±1.1 | 40℃ 99.2±1.5 99.4±1.0 99.3±1.1 100.2±1.5 97.8±1.5 | 25℃ 99.2±1.5 100.3±1.1 98.4±1.5 100.4±1.6 100.8±1.3 | (4500±500)lx 99.2±1.5 100.0±1.7 100.2±1.2 98.7±1.1 100.2±1.1 |
| 10 | 96.8±1.4 | 95.7±1.2 | 97.3±1.1 | 99.0±1.7 | 99.2±1.3 | |
2.6 the safety evaluatio of nanometer berberine hydrochloride emulsion
Get 40 of mices, be divided into 5 groups at random, 8 every group, difference nano-emulsion medicinal liquid 0.2,0.25,0.3,0.35, the drug level that 0.4g/ml is different is irritated stomach.Dosage is 0.2ml/10g, and successive administration 7d observes 7d after the administration, freely drinks water and takes food, and writes down symptom, sign and mortality thereof and time after each treated animal administration, writes down its death toll, calculates LD with the Bliss method
50Software program (Huaxi Medical Univ's establishment) is handled.Its LD as a result
50Be 3055mg/kg.Belong to the avirulence medicine.The result shows that it is very safe.
Test example 2: antibacterial activity in vitro relatively
1 experiment material and instrument
The strain that this experiment is selected down is escherichia coli, staphylococcus, streptococcus, dysentery bacterium and Salmonella, strain from microorganism teaching and research room of Xibei Univ. of Agricultural ﹠ Forest Science ﹠ Technology.Experimental drug has berberine hydrochloride tablet, berberine hydrochloride capsule, and similar antimicrobial SANHUANG PIAN and SHUANGHUANGLIAN KOUFUYE are all commercially available.Berberine aqueous solution and blank nano-emulsion and berberine nano-emulsion thereof are all made by oneself.Experimental apparatus is Xibei Univ. of Agricultural ﹠ Forest Science ﹠ Technology's laboratory and is existing instrument.
2 experimental techniques
2.1 the grouping of experiment and preparation culture medium
Experiment is divided into: normal group, berberine aqueous solution, berberine hydrochloride tablet, berberine hydrochloride capsule, nanometer berberine hydrochloride emulsion, blank nano-emulsion, SANHUANG PIAN and SHUANGHUANGLIAN KOUFUYE group.
Accurately taking by weighing Nutrient agar 100g is dissolved in the 200ml sterilized water and makes culture medium.
2.2 preparation escherichia coli, staphylococcus, streptococcus, Bacillus typhi and Salmonella suspension
Get escherichia coli, staphylococcus, streptococcus respectively, dysentery bacterium and Salmonella original seed are dissolved in the 10ml sterilized water, vibrate suspension.
2.3 inoculated and cultured
Take by weighing the berberine aqueous solution respectively, berberine hydrochloride tablet, berberine hydrochloride capsule, nanometer berberine hydrochloride emulsion, blank nano-emulsion, each 0.01g of SANHUANG PIAN and SHUANGHUANGLIAN KOUFUYE is dissolved in the 10ml sterilized water, the scraps of paper that are 6mm with 105 diameters divide 35 parts to soak wherein 2min earlier, and the scraps of paper after the immersion place 35 culture dishs.Oven dry (about 20min) in 60 ℃ drying baker. wherein the scraps of paper of normal group do not soak. under the sterile working, in culture dish, add the 0.02ml escherichia coli earlier, staphylococcus, streptococcus, the suspension of dysentery bacterium and Salmonella and the culture medium of 20ml, to contain the good scraps of paper of above-mentioned oven dry then is 3 parts, place respectively and contain escherichia coli, staphylococcus, streptococcus, in the culture dish of Bacillus typhi and Salmonella, observed result after temperature is to cultivate 48h in 37 ℃ the incubator, measure the diameter (cm) of antibacterial ring, the diameter of antibacterial ring is big, then good antimicrobial effect. and carry out statistical analysis with SSPP11.0.
3. experimental result
Experimental result the results are shown in Table 3. and from table 3 explanation berberine nano-emulsion above-mentioned antibacterial is all had better antibacterial activity.
Table 3 extracorporeal bacteria inhibitor test is n=3 as a result
| Group name | The reflection time | The diameter of antibacterial ring (cm) (x+s) | |
| Escherichia coli staphylococcus streptococcus shigella dysenteriae salmonella | Normal group berberin HCL tablet berberine aqueous solution Halomine capsule nanometer berberine hydrochloride emulsion; Blank nano-emulsion sanhuang tablets, sanhuang pian sheet shuanghuanglian mixture, shuanghuanglian koufuye normal group berberin HCL tablet berberine aqueous solution Halomine capsule nanometer berberine hydrochloride emulsion; Blank nano-emulsion sanhuang tablets, sanhuang pian shuanghuanglian mixture, shuanghuanglian koufuye normal group berberin HCL tablet berberine aqueous solution Halomine capsule nanometer berberine hydrochloride emulsion; Blank nano-emulsion sanhuang tablets, sanhuang pian shuanghuanglian mixture, shuanghuanglian koufuye normal group berberin HCL tablet berberine aqueous solution Halomine capsule nanometer berberine hydrochloride emulsion, the blank nano-emulsion sanhuang tablets, sanhuang pian shuanghuanglian mixture, shuanghuanglian koufuye normal group berberin HCL tablet berberine aqueous solution | 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h 48h | 0 1.12+0.02 a 1.10+0.03 a 1.15+0.02 a 1.45+0.01 b 0.02+0.02 1.25+0.01 b 1.30+0.02 b 0 0.95+0.03 0.88+0.05 a 1.02+0.02 b 1.35+0.06 b 0.03+0.02 1.15+0.03 b 1.20+0.01 b 0 1.05+0.03 1.0+0.02 a 1.05+0.02 a 1.55+0.01 b 0.02+0.02 1.25+0.01 b 1.30+0.02 b 0 1.42+0.03 1.35+0.03 a 1.48+0.02 a 1.67+0.01 b 0.05+0.03 1.35+0.05 b 1.40+0.04 b 0 0.72+0.08 0.65+0.03 a |
| Berberine hydrochloride capsule nanometer berberine hydrochloride emulsion, blank nano-emulsion SANHUANG PIAN | 48h 48h 48h 48h | 0.75+0.07 a 1.25+0.01 b 0.01+0.04 1.00+0.03 b | |
| SHUANGHUANGLIAN KOUFUYE | 48h | 1.05+0.02 b |
Remarks: compare P＜0.05 with normal group, significant difference is a; Compare P＜0.01 with normal group, difference is extremely remarkable, is b.X is a standard deviation for meansigma methods s.
Test example 3: hypoglycemic activity research
1 experiment material
Experimental drug has berberine hydrochloride tablet, berberine hydrochloride capsule, similar three yellow preparation is made up of Rhizoma Coptidis rope, baicalin and astragalus polysaccharides. and facing the time spent is mixed with suspendible liquid with gumwater, alloxan, glyburide (glibenclamide sheet), glucose assays test kit (GOD-PAP method) are all commercially available.Blank nano-emulsion and berberine nano-emulsion thereof are all made by oneself.ICR is a mice. the male and female dual-purpose, body weight 22-25g is provided by The Fourth Military Medical University experimental animal center.
2 experimental techniques
2.1 experiment grouping:
Experiment is divided into normal group, model group, blank nano-emulsion group, berberine hydrochloride tablet group, berberine hydrochloride Capsules group, nanometer berberine hydrochloride emulsion group, three yellow preparation group, glyburide group.
2.2 experimental technique
Getting 140 of mices. water 12h is can't help in fasting, and tail vein injection alloxan (95mg/kg) normal saline solution 72h posterior orbit vein is got blood. and measure fasting 12h mouse blood sugar value with the GOD-PAP method, choose blood glucose value and be the moulding success 80 of 200-500mg/dl persons.Animal is divided into 8 groups at random. each mice body weight of weighing .1 time/d. of intravenously administrable is 12d altogether.In addition with 30 mouse tail vein injection equal-volume normal saline. get wherein 20 blood glucose values are measured mice behind the fasting 12h respectively for 6d after the administration of normal control group and 12d. near the person blood glucose value.
3. experimental result
Experimental result sees Table 4.By table 4 as seen, to compare with normal group. alloxan model group mouse blood sugar value significantly raises (P＜0.001), shows the model success.Behind successive administration 6d and the 12d, treatment group blood glucose value all significantly descends.The best results of berberine hydrochloride nanometer.
The influence of table 4 pair model mice blood glucose
| Group | Dosage (C/g.kg-1) | Number of animals | Blood glucose value (C/mg.dl-1) | ||
| Before the administration (x ± s) | 6d after the administration (x ± s) | 12d after the administration (x ± s) | |||
| The blank nano-emulsion group of normal group model group berberin HCL tablet group Halomine Capsules group nanometer berberine hydrochloride emulsion group three yellow preparation group | NS NS 0.25 0.55 0.56 0.56 1.80 | 10 10 10 10 10 10 10 | 100.5+21.6 389.7+55.6 b 369.4+65.6 b 399.3+45.6 b 400.8+55.6 b 400.9+51.6 b 390.1+55.6 b | 113.4+31.8 416.8+88.5 400.5+28.5 378.7+78.5 a* 369.9+88.5 b* 250.1+88.5 b** 358.4+88.5 b** | 97.9+32.6 400.2+22.5 401.3+23.5 358.2+62.5 b* 348.1+28.5 b** 240.2+26.5 b** 325.4+22.5 b** |
| The glyburide group | 0.03 | 10 | 395.5+80.6 b | 280.7+58.5 b** | 264.2+21.5 b** |
Compare P＜0.05 with normal group, significant difference is a; Compare P＜0.01 with normal group, difference is extremely remarkable, is b; Compare with model group, compare P＜0.05 with normal group, significant difference is *; Compare P＜0.01 with normal group, difference is extremely remarkable, is * *.X is a standard deviation for meansigma methods s.
Embodiment 1: nanometer berberine hydrochloride emulsion oral soft capsule preparation
1) takes by weighing berberine hydrochloride 0.1g, n-butyl alcohol 5g, tween 80 20g, Arlacel-80 10g, medicinal IPM 24g, mannitol 2g, distilled water 38.9g.
2) with tween 80, the berberine hydrochloride mixing of described weight, and stir in the 200rpm constant temperature blender with magnetic force, temperature allows berberine hydrochloride be partly dissolved under 80 ℃;
3) RH-40 and the n-butyl alcohol that adds described weight again dissolves fully by berberine hydrochloride, obtains clear solution;
4) add the medicinal IPM of described weight again, in 80 ℃ of waters bath with thermostatic control, add half dissolved in distilled water clear solutions of described weight;
5) add at last the sweeting agent of described weight and add half distilled water of described weight again, mixing promptly gets nanometer berberine hydrochloride emulsion medicine of the present invention;
6) soft capsule of packing into.
Embodiment 2: the nanometer berberine hydrochloride emulsion oral liquid formulations
1) take by weighing berberine hydrochloride 0.2g, glycerol 5g, tween 80 16g, Arlacel-80 8g, medicinal liquid paraffin 6g, sucrose 2g, distilled water 62.8g, standby; Step 2), 3), 4), 5) identical with embodiment 1;
6) directly oral liquid is packed in glass or the plastic tube (with having had glass now or the plastic tube preparation method is prepared).
Embodiment 3 nanometer berberine hydrochloride emulsion oral liquid formulations
1) take by weighing berberine hydrochloride 0.2g, dehydrated alcohol 5g, Tween-60 16g, Arlacel-80 8g, salad oil 6g, mannitol 5g, distilled water 59.8g, standby; Step 2), 3), 4), 5), 6) together
Embodiment 2 is identical.
Embodiment 4: the nanometer berberine hydrochloride emulsion oral capsule preparation
1) take by weighing berberine hydrochloride 0.3g, dehydrated alcohol 5g, the medicinal IPM 30g of tween 80 20g, Arlacel-80 10g, mannitol 5g, distilled water 29.7g, standby; Step 2), 3), 4), 5) together
Embodiment 1 is identical;
6) with above-mentioned 5) the nanometer berberine hydrochloride emulsion medicament freeze-drying of gained becomes powder, in it is incapsulated.
Embodiment 5: the nanometer berberine hydrochloride emulsion oral liquid formulations
1) take by weighing berberine hydrochloride 0.5g, dehydrated alcohol 10g, ethyl oleate 20g, Arlacel-80 10g, triglyceride 30g, sucrose 3g, distilled water 27.5g, standby; Step 2), 3), 4), 5) 6) together
Embodiment 2 is identical.
Embodiment 6: nanometer berberine hydrochloride emulsion oral soft capsule preparation
1) take by weighing berberine hydrochloride 0.5g, 1,3 butanediol 5g, tween 80 14g, Arlacel-60 7g medicinal liquid paraffin 9g, mannitol 5g, distilled water 64.5g, standby; Step 2), 3), 4), 5), 6) identical with embodiment 1.
Embodiment 7: nanometer berberine hydrochloride emulsion oral soft capsule preparation
1) take by weighing berberine hydrochloride 1g, glycerol 10g, tween 80 10g, Arlacel-80 5g, medicinal liquid paraffin 15g, mannitol 4g, distilled water 55g, standby; Step 2), 3), 4), 5), 6) identical with embodiment 1.
Embodiment 8: the nanometer berberine hydrochloride emulsion oral liquid formulations
1) take by weighing berberine hydrochloride 1.5g, glycerol 10g, tween 80 14g, Arlacel-80 7g, Oleum Glycines 9g, mannitol 5g, distilled water 63.5g, standby; Step 2), 3), 4), 5), 6) identical with embodiment 2.
Embodiment 9: nanometer berberine hydrochloride emulsion oral soft capsule preparation
1) take by weighing berberine hydrochloride 1.5g, glycerol 10g, RH-40 14g, Arlacel-80 7g, medicinal liquid paraffin 9g, mannitol 5g, distilled water 63.5g, standby; Step 2), 3), 4), 5), 6) identical with embodiment 1.
Embodiment 10: the nanometer berberine hydrochloride emulsion oral capsule preparation
1) take by weighing berberine hydrochloride 2g, glycerol 10g, RH-40 14g, Arlacel-80 7g, Oleum Ricini 9g, sucrose 5g, distilled water 63g, standby; Step 2), 3), 4), 5), 6) identical with embodiment 4.
Claims (2)
1. nanometer berberine hydrochloride emulsion preparation, said preparation is made up of the berberine hydrochloride of 0.1%-2%, the solvent of 1%-10%, the surfactant of 20%-40%, the cosurfactant of 10%-20%, the oil phase of 5%-30%, the sweeting agent of 1%-5%, the distilled water of 27.5%-70%;
Described surfactant be in Tween-60, triglyceride, tween 80, the polyoxyethylene hydrogen flower Oleum Ricini any;
Described cosurfactant is any in Arlacel-80 and the sorbester p18;
Described oil is any in edible soybean oil, medicinal liquid paraffin, edible salad oil, Oleum Ricini, isopropyl myristate, the ethyl oleate;
Described solvent is any in dehydrated alcohol, n-butyl alcohol, glycerol, the 1,3 butylene glycol;
Described sweeting agent is sucrose or mannitol.
2. prepare the preparation method of the described nanometer berberine hydrochloride emulsion preparation of claim 1, it is characterized in that: may further comprise the steps:
1) it is standby to take by weighing berberine hydrochloride, solvent, surfactant, cosurfactant, oil phase, sweeting agent, distilled water by prescription;
2) with the surfactant and the berberine hydrochloride mixing of described amount, and be that 100～300r/m constant temperature blender with magnetic force stirs at rotating speed, temperature allows berberine hydrochloride be partly dissolved under 60～80 ℃ earlier;
3) cosurfactant and the solvent that adds described amount again dissolves fully by berberine hydrochloride, obtains clear solutions;
4) add the oil phase of described amount again, 80 ℃ of waters bath with thermostatic control, and be that 100～300r/m constant temperature blender with magnetic force stirs at rotating speed, adding distilled water, obtain clear solutions;
5) add at last the sweeting agent and the distilled water of described amount again, mixing obtains the solution of clear, promptly gets product of the present invention.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101044182A CN100528155C (en) | 2006-07-31 | 2006-07-31 | Nanometer berberine hydrochloride emulsion and its preparation process |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
| CN101623255B (en) * | 2008-07-08 | 2010-12-29 | 中国农业科学院兰州畜牧与兽药研究所 | Artesunate nanoemulsion drug composition and preparation method thereof |
| CN103462892A (en) * | 2007-11-28 | 2013-12-25 | 联邦科学和工业研究组织 | Nanoemulsions |
| CN104430400A (en) * | 2014-11-20 | 2015-03-25 | 天津农学院 | Instant berberine preparation, preparation method and application thereof |
| CN104825389A (en) * | 2015-04-10 | 2015-08-12 | 广东药学院 | Berberine hydrochloride self-microemulsion preparation having good oral bioavailability and preparation method thereof |
| CN104940167A (en) * | 2015-06-05 | 2015-09-30 | 厦门大学 | Preparation method for berberine-loaded phospholipid composite nanoparticles |
| CN106729739A (en) * | 2016-11-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | One kind is without palatability high content berberine sulphate oral liquid and preparation method thereof |
| CN107997987A (en) * | 2017-12-25 | 2018-05-08 | 东莞霖诺盈生物科技有限公司 | Hyaluronic acid nanometer emulsion formulation and preparation method thereof |
| CN110200833A (en) * | 2019-06-03 | 2019-09-06 | 五邑大学 | A kind of phloretin nano-emulsion preparation and its preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103462892A (en) * | 2007-11-28 | 2013-12-25 | 联邦科学和工业研究组织 | Nanoemulsions |
| US9649275B2 (en) | 2007-11-28 | 2017-05-16 | Commonwealth Scientific And Industrial Research Organisation | Nanoemulsions |
| CN101623255B (en) * | 2008-07-08 | 2010-12-29 | 中国农业科学院兰州畜牧与兽药研究所 | Artesunate nanoemulsion drug composition and preparation method thereof |
| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
| CN104430400A (en) * | 2014-11-20 | 2015-03-25 | 天津农学院 | Instant berberine preparation, preparation method and application thereof |
| CN104825389A (en) * | 2015-04-10 | 2015-08-12 | 广东药学院 | Berberine hydrochloride self-microemulsion preparation having good oral bioavailability and preparation method thereof |
| CN104825389B (en) * | 2015-04-10 | 2018-03-16 | 广东药学院 | A kind of Berberine hydrochloride self-micro emulsion formulation and preparation method thereof |
| CN104940167A (en) * | 2015-06-05 | 2015-09-30 | 厦门大学 | Preparation method for berberine-loaded phospholipid composite nanoparticles |
| CN104940167B (en) * | 2015-06-05 | 2018-01-23 | 厦门大学 | A kind of preparation method for loading berberine phosphatide composite nano particle |
| CN106729739A (en) * | 2016-11-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | One kind is without palatability high content berberine sulphate oral liquid and preparation method thereof |
| CN107997987A (en) * | 2017-12-25 | 2018-05-08 | 东莞霖诺盈生物科技有限公司 | Hyaluronic acid nanometer emulsion formulation and preparation method thereof |
| CN110200833A (en) * | 2019-06-03 | 2019-09-06 | 五邑大学 | A kind of phloretin nano-emulsion preparation and its preparation method and application |
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