CN102961417B - Traditional Chinese medicine multicomponent micro-emulsion composition having function of resisting lung cancer, preparation method and application thereof in preparation of orally-taking lung cancer resistant medicine - Google Patents
Traditional Chinese medicine multicomponent micro-emulsion composition having function of resisting lung cancer, preparation method and application thereof in preparation of orally-taking lung cancer resistant medicine Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine multicomponent micro-emulsion composition having a function of resisting lung cancer, a preparation method and application thereof in preparation of an orally-taking lung cancer resistant medicine. The application comprises the following steps of: adding ganoderma lucidum total triterpenes, coixenolide, ganoderan and semen coicis polysaccharide used as raw material medicines into a nano-medicine composition which consists of surfactants and cosurfactant, wherein the traditional Chinese medicine multicomponent micro-emulsion composition comprises the following components in parts by weight: 5-30 parts of ganoderma lucidum total triterpenes, 45-150 parts of coixenolide, 5-50 parts of ganoderan and 10-90 parts of semen coicis polysaccharide, 45-200 parts of surfactants, 20-100 parts of cosurfactant and 300-900 parts of distilled water. The invention also discloses a preparation method of the composition. The ganoderma lucidum total triterpenes and the coixenolide are carried into a non-water phase, and the lucid ganoderma and the semen coicis polysaccharide are carried into a water phase, so that the coixendide can be used as medicines and also can be used as an auxiliary; the polysaccharide can enhance the immunization and the stability of a micro-emulsion system; and by the micro-emulsion, the absorption of the ganoderma lucidum total triterpenes and coixenolide used as the lipid solubility components can be increased, and the matching of four components have a synergy anti-tumor effect so as to increase the anti-tumor effect.
Description
Technical field
The present invention relates to the anti-pulmonary carcinoma microemulsion of a kind of Chinese medicine multicomponent, water-insoluble drug Ganoderma total triterpenes and coixenolide are loaded in nonaqueous phase by this nano-composition, ganoderan and coixan are loaded in aqueous phase, are prepared into multicomponent micro emulsion composition.The invention still further relates to the preparation method of this micro emulsion composition.
Background technology
Pulmonary carcinoma is global first cancer killer at present, and the whole world is newly-increased cases of lung cancer 1,200,000 example every year, within every 30 seconds, just has a people to die from pulmonary carcinoma.In China, pulmonary carcinoma is the cancer that incidence and mortality is the highest equally, it is predicted, by 2025, the annual patients with lung cancer of China more than 1,000,000, will become the first in the world pulmonary carcinoma big country.Within 2012, pulmonary carcinoma has been included into medical insurance relief pilot scope.Therefore the research and development of anti-lung-cancer medicament will have great social benefit and economic benefit.
The domestic and international treatment about pulmonary carcinoma at present is mainly performed the operation and radiotherapy, chemotherapy, but these methods easily cause larger side effect to the normal organ of patient, make the survival rate of patient lower.The Chinese medicine being characteristic with " eliminating pathogenic factor for supporting vital QI " has played great function in treatment pulmonary carcinoma, and its curative effect is not only consolidated, and toxic and side effects is little, adds the safety to body medication, with chemotherapy also with the effect can playing attenuation synergistic.
Ganoderma is On Polyporaceae Ganoderma lucidum (Leyss. Ex Fr.) Karst.
ganoderma lucidum(Leyss. ex Fr.) Karst. or Ganoderma
ganoderma sinensezhao, Xu et Zhang) dry sporophore.Nature and flavor are sweet, flat; GUIXIN, lung, liver, kidney channel.There is invigorating QI and tranquilization, effect of relieving cough and asthma.For malaise, cough and asthma due to lung deficiency, asthenia is losed heart, anorexia etc.Modern scientific research shows, Ganoderma has stronger antitumor action, and wherein Ganoderma total triterpenes is the main active component of its antineoplastic, and ganoderan is the main active component improving immunity of organisms, but the two oral absorption is poor, thus affect the performance of its oral drug effect.
Semen Coicis is grass Semen Coicis
coix lacryma-jobil. var.
mayuen(Roman.) dry mature kernal of Stapf.Nature and flavor are sweet, light, cool; Return spleen, stomach, lung meridian.There is promoting diuresis to eliminate damp pathogen, invigorating the spleen to arrest diarrhea, eliminating impediment, evacuation of pus, effect of detoxicating and resolving stagnation of pathogens.For edema, beriberi, dysuria, diarrhea due to hypofunction of the spleen, arthralgia chiefly caused by damp pathogen contracture, lung abscess, acute appendicitis, wart, cancerous protuberance.Modern study shows, Semen Coicis also has good antitumor action, and wherein coixenolide is its main anti-cancer effective component, and coixan is the main active component improving immunity of organisms, but the two oral artifact availability is lower, thus have impact on the performance of its clinical efficacy.
The medicine composition of multicomponent micro emulsion composition of the present invention derives from clinical anti-pulmonary carcinoma proved recipe, and this proved recipe is made up of Ganoderma and Semen Coicis two taste Chinese medicine, has boosting qi and nourishing yin, promoting diuresis to eliminate damp pathogen, the effect of dispersing tumor softening the hard mass.Wherein Ganoderma total triterpenes and coixenolide are this compound recipe main anti-tumor active component, and ganoderan and coixan are the main active components improving immunity of organisms.At present this compound recipe method of still boiling with traditional water decoction is for patient, but Ganoderma total triterpenes and coixenolide water solublity poor, ganoderan and coixan are macromolecular substances, and oral being all difficult to absorbs, and affects the performance of its drug effect.Therefore the present invention adopts microemulsion as oral drugs carrier, with Ganoderma total triterpenes, coixenolide, ganoderan and coixan four kinds of component compatibilities, coixenolide has the effect of adjuvant concurrently, polysaccharide not only can strengthen immunization but also can increase the stability of microemulsion system, prepare clever heart of a lotus seed side multicomponent micro emulsion composition, to promote drug absorption, play the effect of synergistic antitumor, antitumous effect is strengthened.
Microemulsion is a kind of, low-viscosity, isotropism transparent or semitransparent in the spontaneous one formed of proper proportion by oil phase, aqueous phase, surfactant and cosurfactant and thermodynamically stable oil-water mixing system, there is the dissolubility that can improve poorly water soluble drugs, promote absorption that is fat-soluble and water-soluble macromolecule medicine; Improve the advantages such as the bioavailability of medicine.Because microemulsion is not only containing aqueous phase but also containing nonaqueous phase, be therefore suitable for the load that existing fat-soluble ingredient has again the Chinese medicine compound of water-soluble component.
Through retrieval, prior art is existing to Ganoderma or Semen Coicis antineoplastic related preparations report.About the Chinese patent application of single Semen Coicis oil has: a kind of coix seed oil soft capsule and application (02137311.6) thereof for the treatment of prostatosis, a kind of preparation method (2010101934956.6) of coix seed oil microemulsion, a kind of Semen Coicis oil self-emulsifiable preparation and preparation method thereof (200710027400.1) and a kind of coix seed oil proliposome and preparation method thereof (201010130883.X) etc.About the patent of single Ganoderma total triterpenes has: self-mciro emulsifying nano composition of a kind of ganodenic acid extract of anti-tumor activity and preparation method thereof (200910031997.6).About the patent of Ganoderma and Semen Coicis has: a kind of Ganoderma spore oil and Semen Coicis oil composite intravenous injection emulsion and preparation method thereof (200510135357.1).But there is not yet through document and patent retrieval and the preparation of four class component compatibilities above-mentioned in Ganoderma and Semen Coicis is reported.
Summary of the invention
The object of this invention is to provide a kind of Chinese medicine multicomponent micro emulsion composition with effect of anti-lung cancer and preparation method thereof, and the application of this nano-composition in the oral anti-lung-cancer medicament of preparation.This multicomponent microemulsion can promote the absorption of fat-soluble ingredient Ganoderma total triterpenes and coixenolide, and four kinds of component compatibilities have synergistic antitumor effect, and antitumous effect is strengthened.
First goal of the invention of the present invention is realized by following technical scheme:
A kind of Chinese medicine multicomponent micro emulsion composition with effect of anti-lung cancer, using Ganoderma total triterpenes, coixenolide and ganoderan, coixan as crude drug, wherein coixenolide is double does oil phase, ganoderan, coixan are soluble in the aqueous phase, it is characterized in that, the nano-composition that described crude drug forms with surfactant and cosurfactant, each ingredients weight parts is as follows:
Ganoderma total triterpenes 5-30 part, coixenolide 45-150 part, surfactant 45-200 part, cosurfactant 20-100 part, ganoderan 5-50 part, coixan 20-100 part, distilled water 300-900 part.
The optimized proportion of each ingredients weight parts is:
Ganoderma total triterpenes 10-25 part, coixenolide 60-120 part, surfactant 60-150 part, cosurfactant 30-80 part, ganoderan 10-40 part, coixan 50-90 part, distilled water 400-800 part.
The ratio more optimized of each ingredients weight parts is:
Ganoderma total triterpenes 12-20 part, coixenolide 75-90 part, surfactant 75-100 part, cosurfactant 35-60 part, ganoderan 15-25 part, coixan 60-80 part, distilled water 500-600 part.
Above-mentioned Ganoderma total triterpenes refers to and Ganoderma sporophore is passed through supercritical CO
2the method extraction of extraction obtains, and idiographic flow is as follows: loaded by Ganoderma coarse powder in extraction kettle, and the pressure of setting extraction kettle is 25 MPa, and extraction temperature is 45 DEG C, and extraction time is 1.5 h, and the consumption of entrainer (95% ethanol) is the medical material of 3 times amount; Separation reactor I pressure is 7 MPa, and temperature is 50 DEG C; Separating still II pressure is 4 MPa, and temperature is 36 DEG C; CO in extraction equipment
2flow-control is at 30 Lh
-1.When after the extraction time reaching test setting, receive extract from separation reactor I and separation reactor I I discharging opening, combining extraction liquid, recycling design, 50 DEG C of vacuum dryings, obtaining Ganoderma total triterpenes purity is 61%(spectrophotometry, in ursolic acid) extract.
Above-mentioned coixenolide refers to and Semen Coicis is passed through supercritical CO
2the method extraction of extraction obtains, and idiographic flow is as follows: loaded by Semen Coicis coarse powder in extraction kettle, and the pressure of setting extraction kettle is 22 MPa, and extraction temperature is 38 DEG C; Extraction time is 2.5 h, extracting twice; The consumption of entrainer (95% ethanol) is the medical material of 3 times amount; Separation reactor I pressure is 8 MPa, and temperature is 48 DEG C; Separation reactor I I pressure is 4 MPa, and temperature is 26 DEG C; CO in extraction equipment
2flow-control is at 30 Lh
-1.When after the extraction time reaching test setting, receive extract, combining extraction liquid from separation reactor I and separation reactor I I discharging opening, recycling design, 50 DEG C of vacuum dryings, obtaining coixenolide purity is 74%(spectrophotometry, in triolein) extract.
Above-mentioned ganoderan, coixan refer to respectively by Ganoderma sporophore, Semen Coicis supercritical CO
2obtain after medicinal residues water extract-alcohol precipitation after extraction, idiographic flow is as follows: get supercritical CO
2ganoderma sporophore coarse powder after extraction or Semen Coicis coarse powder residue, add the water of 12 times amount, reflux, extract, 2 times, each 1 h, merge extracted twice liquid, centrifugal filtering, filtrate concentrates, add alcohol settling, solution alcohol content is made to be 80%, hold over night, filter, by precipitation water dissolution, add Sevag reagent (n-butyl alcohol: chloroform=1:5) jolting 30 min of 1/5 volume, centrifugal, the denatured protein of branch vibration layer and solvent layer intersection, the water layer obtained will be separated, concentrated, vacuum drying, obtain Ganoderma or coixan extract, its purity of polysaccharide is respectively 55%, 58%(spectrophotometry, with glucose meter).
Above-mentioned surfactant can be selected from following compound one or more: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether;
Above-mentioned cosurfactant can be selected from following compound one or more: ethanol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400, or ethylene glycol monomethyl ether.
The present invention is based on clinical anti-pulmonary carcinoma proved recipe " clever heart of a lotus seed side ", under the guidance of Chinese medical theory, the Medicinal Trait having given full play to Chinese medicine multicomponent Mutiple Targets and compatibility administration designs a kind of multicomponent micro emulsion drug carrying system, and in existing patent and document, not yet find the report of the microemulsion and preparation method thereof about Ganoderma total triterpenes, coixenolide, ganoderan and coixan compatibility.Compatibility is a large characteristic of Chinese medicine medication, and the Ganoderma total triterpenes in the present invention and coixenolide are all the definite components of antitumor curative effect, and ganoderan and coixan are all the components improving immunity determined curative effect.The present invention by a large amount of experimental studies have found that Ganoderma total triterpenes, coixenolide, ganoderan and coixan compatibility after, Ganoderma total triterpenes and coixenolide compatibility all demonstrate synergism to cell death inducing inhibition tumor cell propagation and cell cycle arrest aspect.Ganoderma total triterpenes and coixenolide compatibility use and can activate Caspase-3, Caspase-9 and Caspase-8, obvious downward Bcl-2 protein level, shows that Ganoderma total triterpenes and the apoptotic associated protein of coixenolide compatibility controllable promote the inhibitory action to tumor cell proliferation.Ganoderma total triterpenes and coixenolide compatibility ganoderan and coixan oral after, the liver index of tumor animal, thymus index, spleen index are significantly increased (P<0.05) with amynologic index such as TNF-α, IL-6 content in blood plasma compared with the polysaccharide that is incompatible, and embody the effect of multipath synergistic antitumor.
Early-stage Study of the present invention also finds Ganoderma total triterpenes, coixenolide, the intestinal absorption of ganoderan and coixan is poor, for overcoming above-mentioned defect, the antitumous effect of component compatibility in the clever heart of a lotus seed side of better performance, the present invention is directed to Ganoderma total triterpenes, coixenolide, the physicochemical property of ganoderan and coixan, adopt and be applicable to the multi-component microemulsion of Chinese medicine as carrier, the technological difficulties that multicomponent is difficult to be prepared into microemulsion are overcome by a large amount of screening tests, Ganoderma total triterpenes is fat-soluble medicine, coixenolide is double does oil phase, be loaded in nonaqueous phase, ganoderan and coixan are water soluble drug, be loaded in aqueous phase, select suitable surfactant and cosurfactant, prepare the microemulsion drug-supplying system of Chinese medicine multicomponent medicine carrying, this drug-supplying system had both played Ganoderma total triterpenes, coixenolide, Ganoderma and the effect of coixan compatibility synergistic antitumor, facilitate again the absorption of above-mentioned four kinds of components, reduce the consumption of adjuvant simultaneously, polysaccharide adds the stability that aqueous phase can also increase microemulsion system, in addition oral administration route enhances the compliance of patient, avoid the safety issue that drug administration by injection is potential, make preparation safer, stable.
The technical scheme completing the application's second invention task is, the above-mentioned preparation method with the Chinese medicine multicomponent micro emulsion composition of effect of anti-lung cancer, and step is as follows:
(1) precision takes ganoderan and coixan in proportion, is dissolved in the distilled water of recipe quantity, is prepared into aqueous phase, for subsequent use;
(2) another extracting container, precision takes Ganoderma total triterpenes and is put in container in proportion, adds coixenolide, mixes, make medicine dissolution under magnetic stirring apparatus;
(3) connect step 2, then add surfactant, cosurfactant, mix under magnetic stirring apparatus;
(4) connect step 3, the aqueous phase prepared by step 1, instillation is containing in the nonaqueous phase of Ganoderma triterpenoids, coixenolide, surfactant and cosurfactant, and stirring and evenly mixing, obtains the anti-pulmonary carcinoma micro emulsion composition of a kind of multicomponent;
Chinese medicine multicomponent microemulsion prepared by the present invention stirs under magnetic stirring apparatus and can be formed.
Chinese medicine multicomponent microemulsion of the present invention directly can be taken with the form of oral liquid.
Compare with submicron emulsion (100-10000 nm) with conventional creams, microemulsion particle diameter less (10-100 nm), belongs to thermodynamic stable system; Owing to there is aqueous phase and nonaqueous phase in O/W type microemulsion formulation, be suitable for the load that Chinese medicine compound contains water solublity and fat-soluble active component, microemulsion formulation preparation technology is simple, is easy to industrialization, has good industrialization prospect.
The technical scheme of the 3rd goal of the invention of the present invention is: the above-mentioned application of Chinese medicine multicomponent micro emulsion composition in the oral anti-lung-cancer medicament of preparation with effect of anti-lung cancer.
1. adopt the effect of anti-lung cancer of animal model to " clever heart of a lotus seed side " multicomponent microemulsion to carry out evaluating drug effect.
Be adjusted to by cell density is 1 × 10
7the Lewis lung cancer cell suspension inoculation of individual/mL is subcutaneous in the right armpit of C57BL/6 mice, every only 0.2 mL.Next day after inoculation, weigh, random packet, often organizes 8.Blank group: normal saline, every day 0.4 mL/ time; Positive controls: cyclophosphamide (20 mgg
-1d
-1), every day 0.2 mL/ time; Medicine group: the microemulsion that Ganoderma total triterpenes+coixenolide+ganoderan+coixan suspension (weight ratio 1:5:1.2:4.7), Ganoderma total triterpenes+coixenolide+ganoderan+coixan (weight ratio 1:5:1.2:4.7) form, dosage is 3.0 gkg
-1d
-1, every day 0.4 mL/ time.Cyclophosphamide positive controls is lumbar injection, and other are gastric infusion.Successive administration 14 d, every day period weighs, and observes the situation such as general activity, hair of mice.Drug withdrawal next day, weigh, de-neck puts to death mice, peels off oxter tumor, liver, Thymus and spleen.Calculate tumour inhibiting rate, liver index, thymus index and spleen index.The results are shown in Table 1,2.
The average tumor of tumour inhibiting rate (%)=(model group average tumor weight-administration group average tumor weight)/model group heavy × 100%;
Liver index (mg/g)=liver weight (mg)/Mouse Weight (g);
Thymus index (mg/g)=thymic weight (mg)/Mouse Weight (g);
Spleen index (mg/g)=spleen weight (mg)/Mouse Weight (g).
Table 1 " clever heart of a lotus seed side " active component compatibility suspension and microemulsion thereof to the inhibitory action of Lewis tumor-bearing mice tumor (
±
s,
n=8)
| Group | Body weight (g) | Tumor heavy (g) | Tumour inhibiting rate (%) |
| Normal saline | 23.86±2.36 | 5.42±0.91 | ---- |
| Cyclophosphamide | 16.73±1.69 | 1.38±0.48* | 74.59 |
| Ganoderma total triterpenes+coixenolide+ganoderan+coixan (1:5:1.2:4.7) suspension | 19.94±2.02 | 2.93±0.44* | 45.89 |
| Ganoderma total triterpenes+coixenolide+ganoderan+coixan (1:5:1.2:4.7) microemulsion | 20.81±1.02 | 2.32±0.71* | 57.25 |
Note: * is each group and compares (* p<0.05) with normal saline group.
Result shows to compare with normal saline group, the Ganoderma total triterpenes that the present invention obtains, coixenolide, ganoderan, coixan Four composition suspension and microemulsion all have significance inhibitory action to the growth of Lewis tumor in body, and the antitumous effect of microemulsion will be much better than suspension.Illustrate and adopt modern extraction and isolation means and novel nano drug-supplying system by farthest extraction and isolation, the compatibility be prepared into microemulsion of the active component in this pharmaceutical composition, synergistic antitumor effect can be played better.
Table 2 " clever heart of a lotus seed side " active component compatibility suspension and microemulsion thereof on the impact of Lewis tumor-bearing mice immune organ (
±
s,
n=8)
| Group | Liver index (mg/g) | Thymus index (mg/g) | Spleen index (mg/g) |
| Normal saline | 42.94±0.56# | 0.67±0.10# | 4.48±0.45# |
| Cyclophosphamide | 30.10±0.36* | 0.25±0.09* | 2.84±0.62* |
| Ganoderma total triterpenes+coixenolide+ganoderan+coixan (1:5:1.2:4.7) suspension | 60.36±1.26 *# | 1.10±0.31*# | 7.78±0.82*# |
| Ganoderma total triterpenes+coixenolide+ganoderan+coixan (1:5:1.2:4.7) microemulsion | 69.29±2.35*# | 1.29±0.41*# | 8.69±0.97*# |
Note: * is each group and compares (* p<0.05) with normal saline group, and # is each group and compares (# p<0.05) with cyclophosphamide group.
Result shows, compares with normal saline group, and the liver index of cyclophosphamide administration group mice, spleen index, thymus index all have certain reduction, may cause because cyclophosphamide has inhibitory action to mouse immune system.Compared with cyclophosphamide administration group, the animal immune index of the multicomponent microemulsion of Ganoderma total triterpenes+coixenolide+ganoderan+coixan suspension and composition thereof all has significance to improve (p<0.05), illustrates that " clever heart of a lotus seed side " of the present invention multicomponent microemulsion is by the effect of enhancing human body immunity activation plays synergistic antitumor.
The beneficial effect of the Chinese medicine multicomponent microemulsion prepared by the present invention and preparation method thereof shows following several respects:
1, Chinese medicine multicomponent microemulsion preparation method provided by the invention is simple, can complete, easily realize industrialized great production without the need to special installation.
2, the surfactant selected by the present invention and cosurfactant, have the advantages such as safe, nontoxic, nonirritant, microemulsion even particle size distribution, mean diameter is less, between 10-100 nm, is conducive to the absorption of effective ingredient, and antitumous effect is better.
3, the coixenolide of the present invention's use is as oil phase, both improves drug effect, and additionally reduces the consumption of adjuvant, and can reduce oral dose, and saved production cost simultaneously; The polysaccharide component that the present invention uses not only has enhancing immunity, synergistic antitumor effect, can also increase the stability of microemulsion system.
4, the present invention is under the guidance of Chinese medical theory, fully applies Chinese medicine compatibility theory, has made active component compatibility in " clever heart of a lotus seed side " play the antitumor drug effect of working in coordination with.
5, the present invention is applicable to the oral administration characteristic of Chinese medicine, and drug safety is improved greatly, and good patient compliance.
Accompanying drawing explanation
Fig. 1 is the grain size distribution of Chinese medicine multicomponent microemulsion prepared by embodiment 1, and Fig. 2 is the transmission electron microscope picture of Chinese medicine multicomponent microemulsion prepared by embodiment 1.
Detailed description of the invention
Below in conjunction with example, the present invention is described in further detail, but scope of the present invention should be noted not by any restriction of these examples.
Embodiment 1:
Prescription: Ganoderma total triterpenes 4.5g, coixenolide 24g, ganoderan 5.4g, coixan 23.4g, polyoxyethylene hydrogenated Oleum Ricini 24g, PEG400 12g, distilled water 156g.
Take ganoderan and coixan by recipe quantity precision, be dissolved in the distilled water of recipe quantity, be prepared into aqueous phase, for subsequent use;
Another extracting container, takes Ganoderma total triterpenes in prescription ratio precision and is put in container, add coixenolide, mix, make medicine dissolution under magnetic stirring apparatus, then adds polyoxyethylene hydrogenated Oleum Ricini, the PEG400 of recipe quantity, mixes under magnetic stirring apparatus; With the aqueous phase prepared, water titration (method) is adopted to prepare micro-emulsion nano compositions.
Embodiment 2:
Prescription: Ganoderma total triterpenes 4.5g, coixenolide 27g, ganoderan 6g, coixan 9g, poloxamer 30g, isopropyl alcohol 15g, distilled water 180g.
Preparation method is with embodiment 1.
Embodiment 3:
Prescription: Ganoderma total triterpenes 4.5g, coixenolide 24g, ganoderan 5.4g, coixan 19.5g, Tween 80 24g, ethanol 12g, distilled water 165g.
Preparation method is with embodiment 1.
Embodiment 4:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 5 parts, coixenolide 45 parts, ganoderan 5 parts, coixan 20 parts, 45 parts, surfactant, cosurfactant 20 parts, distilled water 300 parts.
Described surfactant is selected from one of following or their compositions: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether.
Described cosurfactant is selected from one of following or their compositions: ethanol, normal propyl alcohol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400 or ethylene glycol monomethyl ether.
Embodiment 5:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 25 parts, coixenolide 120 parts, ganoderan 40 parts, coixan 90 parts, 150 parts, surfactant, cosurfactant 80 parts, distilled water 800 parts.
Described surfactant is selected from one of following or their compositions: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether.
Described cosurfactant is selected from one of following or their compositions: ethanol, normal propyl alcohol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400 or ethylene glycol monomethyl ether.
Embodiment 6:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 15 parts, coixenolide 80 parts, ganoderan 18 parts, coixan 60 parts, 120 parts, surfactant, cosurfactant 65 parts, distilled water 420 parts.
Described surfactant is selected from one of following or their compositions: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether.
Described cosurfactant is selected from one of following or their compositions: ethanol, normal propyl alcohol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400 or ethylene glycol monomethyl ether.
Embodiment 7:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 12 parts, coixenolide 75 parts, ganoderan 15 parts, coixan 60 parts, 75 parts, surfactant, cosurfactant 35 parts, distilled water 500 parts.
Described surfactant is selected from one of following or their compositions: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether.
Described cosurfactant is selected from one of following or their compositions: ethanol, normal propyl alcohol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400 or ethylene glycol monomethyl ether.
Embodiment 8:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 30 parts, coixenolide 150 parts, ganoderan 50 parts, coixan 100 parts, 200 parts, surfactant, cosurfactant 100 parts, distilled water 900 parts.
Embodiment 9:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 10 parts, coixenolide 60 parts, ganoderan 10 parts, coixan 50 parts, surfactant 60, cosurfactant 30 parts, distilled water 400 parts.
Embodiment 10:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows: Ganoderma total triterpenes 20 parts, coixenolide 90 parts, ganoderan 25 parts, coixan 80 parts, surfactant 100, cosurfactant 60 parts, distilled water 600 parts.
Embodiment 11:
Substantially the same manner as Example 1, but each ingredients weight parts is as follows:
Ganoderma total triterpenes 25 parts, coixenolide 120 parts, 150 parts, surfactant, cosurfactant 80 parts, ganoderan 40 parts, coixan 90 parts, distilled water 400 parts.
Claims (7)
1. one kind has the Chinese medicine multicomponent micro emulsion composition of effect of anti-lung cancer, using Ganoderma total triterpenes, coixenolide and ganoderan, coixan as crude drug, wherein coixenolide is double does oil phase, ganoderan, coixan are soluble in the aqueous phase, it is characterized in that, the nano-composition that described Chinese medicine multicomponent micro emulsion composition is made up of crude drug, surfactant and cosurfactant, its each ingredients weight parts is as follows:
Ganoderma total triterpenes 5-30 part, coixenolide 45-150 part, surfactant 45-200 part, cosurfactant 20-100 part, ganoderan 5-50 part, coixan 20-100 part, distilled water 300-900 part;
Described Ganoderma total triterpenes refers to: Ganoderma sporophore coarse powder is passed through supercritical CO
2the Ganoderma total triterpenes extract that the method extracted obtains, its total triterpene purity >50%; Coixenolide refers to: Semen Coicis coarse powder is passed through supercritical CO
2the Semen Coicis extract that the method extracted obtains, its triolein purity >50%; Ganoderan refers to: by Ganoderma sporophore supercritical CO
2the polyoses extract obtained after medicinal residues water extract-alcohol precipitation after extraction, purity of polysaccharide >50%; Coixan refers to: by Semen Coicis supercritical CO
2the polyoses extract obtained after medicinal residues water extract-alcohol precipitation after extraction, purity of polysaccharide >50%;
Described surfactant be selected from following compound one or more: Tween 80, polysorbate60, polysorbas20, poloxamer, lecithin, sorbester p17, sorbester p18, OP emulsifying agent, polyoxyethylene hydrogenated Oleum Ricini, Labraso, or polyoxyethylene castor oil glycerin ether;
Described cosurfactant be selected from lower following compound one or more: ethanol, normal propyl alcohol, isopropyl alcohol, 1,2-PD, glycerol, n-butyl alcohol, Liquid Macrogol, PEG400 or ethylene glycol monomethyl ether.
2. the Chinese medicine multicomponent micro emulsion composition with effect of anti-lung cancer according to claim 1, it is characterized in that, the weight ratio of described each component is:
Ganoderma total triterpenes 10-25 part, coixenolide 60-120 part, surfactant 60-150 part, cosurfactant 30-80 part, ganoderan 10-40 part, coixan 50-90 part, distilled water 400-800 part.
3. the Chinese medicine multicomponent micro emulsion composition with effect of anti-lung cancer according to claim 2, it is characterized in that, the weight ratio of described each component is:
Ganoderma total triterpenes 12-20 part, coixenolide 75-90 part, surfactant 75-100 part, cosurfactant 35-60 part, ganoderan 15-25 part, coixan 60-80 part, distilled water 500-600 part.
4. the preparation method with the Chinese medicine multicomponent micro emulsion composition of effect of anti-lung cancer according to claim 1, it is characterized in that, step is as follows:
(1) precision takes ganoderan and coixan in proportion, is dissolved in the distilled water of recipe quantity, is prepared into aqueous phase, for subsequent use;
(2) another extracting container, precision takes Ganoderma total triterpenes and is put in container in proportion, adds coixenolide, mixes, make medicine dissolution under magnetic stirring apparatus;
(3) connect step 2, then add surfactant, cosurfactant, mix under magnetic stirring apparatus;
(4) connect step 3, the aqueous phase prepared by step 1, instillation is containing in the nonaqueous phase of Ganoderma triterpenoids, coixenolide, surfactant and cosurfactant, and stirring and evenly mixing, obtains the anti-pulmonary carcinoma micro emulsion composition of a kind of multicomponent;
Wherein, each ingredients weight parts is as follows: Ganoderma total triterpenes 5-30 part, coixenolide 45-150 part, ganoderan 5-50 part, coixan 10-90 part, surfactant 45-200 part, cosurfactant 20-100 part, distilled water 300-900 part.
5. the preparation method with the Chinese medicine multicomponent micro emulsion composition of effect of anti-lung cancer according to claim 4, it is characterized in that, the weight ratio of described each component is:
Ganoderma total triterpenes 10-25 part, coixenolide 60-120 part, surfactant 60-150 part, cosurfactant 30-80 part, ganoderan 10-40 part, coixan 50-90 part, distilled water 400-800 part.
6. the preparation method with the Chinese medicine multicomponent micro emulsion composition of effect of anti-lung cancer according to claim 4 or 5, it is characterized in that, the weight ratio of described each component is:
Ganoderma total triterpenes 12-20 part, coixenolide 75-90 part, surfactant 75-100 part, cosurfactant 35-60 part, ganoderan 15-25 part, coixan 60-80 part, distilled water 500-600 part.
7. the application of Chinese medicine multicomponent micro emulsion composition in the anti-pulmonary carcinoma oral drugs of preparation with effect of anti-lung cancer according to claim 1.
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