CN101601695A - Self-mciro emulsifying nano composition of ganodenic acid extract and preparation method thereof - Google Patents
Self-mciro emulsifying nano composition of ganodenic acid extract and preparation method thereof Download PDFInfo
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- CN101601695A CN101601695A CNA2009100319976A CN200910031997A CN101601695A CN 101601695 A CN101601695 A CN 101601695A CN A2009100319976 A CNA2009100319976 A CN A2009100319976A CN 200910031997 A CN200910031997 A CN 200910031997A CN 101601695 A CN101601695 A CN 101601695A
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- polysorbate
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- 239000000284 extract Substances 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 239000002253 acid Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 36
- 230000001804 emulsifying effect Effects 0.000 title claims abstract description 22
- 238000000605 extraction Methods 0.000 title claims abstract description 9
- 241000222336 Ganoderma Species 0.000 claims abstract description 49
- 150000003648 triterpenes Chemical class 0.000 claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 33
- 239000004094 surface-active agent Substances 0.000 claims abstract description 29
- 239000004064 cosurfactant Substances 0.000 claims abstract description 23
- 239000003921 oil Substances 0.000 claims abstract description 23
- 229940079593 drug Drugs 0.000 claims abstract description 12
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
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- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 claims description 8
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- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 6
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 6
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 6
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- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 5
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 5
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- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 claims description 5
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- 229940093471 ethyl oleate Drugs 0.000 claims description 5
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- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 4
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- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims description 4
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- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 4
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- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 4
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 4
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 4
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 4
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 4
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 claims description 4
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 claims description 4
- 229940068977 polysorbate 20 Drugs 0.000 claims description 4
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- HVUMOYIDDBPOLL-UHFFFAOYSA-N 2-(3,4-Dihydroxyoxolan-2-yl)-2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)C1OCC(O)C1O HVUMOYIDDBPOLL-UHFFFAOYSA-N 0.000 claims description 3
- IJCWFDPJFXGQBN-UHFFFAOYSA-N 2-[4-Hydroxy-3-(octadecanoyloxy)oxolan-2-yl]-2-(octadecanoyloxy)ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)C1OCC(O)C1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-UHFFFAOYSA-N 0.000 claims description 3
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims description 3
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 claims description 3
- 235000011067 sorbitan monolaureate Nutrition 0.000 claims description 3
- PRXRUNOAOLTIEF-WUOFIQDXSA-N sorbitan trioleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C\CCCCCCCC)C1OCC(O)C1OC(=O)CCCCCCC\C=C\CCCCCCCC PRXRUNOAOLTIEF-WUOFIQDXSA-N 0.000 claims description 3
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- Medicinal Preparation (AREA)
Abstract
The self-mciro emulsifying nano composition preparation method of ganodenic acid extract, self-mciro emulsifying nano composition is as crude drug with ganodenic acid extract, the mixture that adopts surfactant, cosurfactant and oil phase composition is as pharmaceutical carrier, it is characterized in that, each ingredients weight parts is as follows: 10 parts of ganodenic acid extracts, 50～400 parts in surfactant, 100～800 parts of cosurfactants, 15～600 parts of oil phases.Described Ganoderma total triterpenes extract is meant: Ganoderma sporophore is passed through supercritical CO
2The Ganoderma total triterpenes extract that the method for extraction extraction obtains.The present invention becomes self microemulsifying preparation with the preparation of water-insoluble drug Ganoderma total triterpenes extract, can improve the dissolution of medicine, promotes drug absorption, helps improving bioavailability; And medicine can be kept dissolved state in intestinal, thereby better disperses permeate through cell membranes, and then improves the drug effect of medicine, and the anti-tumor in vivo effect strengthens.
Description
Technical field
The present invention relates to a kind of self-mciro emulsifying nano composition of ganodenic acid extract, this nano-composition becomes self microemulsifying preparation with the preparation of water-insoluble drug Ganoderma total triterpenes extract, the invention still further relates to the preparation method of this self-mciro emulsifying nano composition.
Background technology
Ganoderma is the Polyporaceae fungus, and medicinal history in several thousand is arranged, and records this agrostology monograph Shennong's Herbal the earliest in China.2,000 for many years, and people prevent, treat tumor with Ganoderma always; Modern scientific research shows that also Ganoderma has stronger antitumor action.
The Ganoderma triterpenoids constituents is acknowledged as one of Ganoderma antineoplastic effective composition.But its water solublity is very poor, influences the performance of its oral absorption and drug effect.
The dosage form of Ganoderma is based on conventional formulation in the market, such as tablet, capsule, granule, chewable tablet, oral liquid etc., even directly Ganoderma broken into fine powder and takes.Disclose a kind of preparation method of Ganoderma triterpenoids constituents chewable tablet as Chinese patent 2005102000612.6, used cyclodextrin inclusion technique, enclose such as ganoderma lucidum triterpene material in cyclodextrin molecular, have been solved the problem of Ganoderma triterpenoids constituents bitter in the mouth.
Though these conventional dosage forms have certain curative effect, but the main active component Ganoderma total triterpenes class component in the Ganoderma is a liposoluble constituent, water solublity is bad, and bioavailability is lower, and it is ultimate attainment that these conventional dosage forms can not make the antitumor action of Ganoderma triterpenoids constituents perform to.The self-microemulsion drug-supplying system can be fit to the Ganoderma triterpenoids constituents and better bring into play drug effect.
(self-microemulsifying drug delivery system SMEDDS) is a kind of novel mode of administration to the self-microemulsion drug-supplying system.It has many-sided advantage, is a kind of ideal form of administration.The appearance of this pharmaceutical dosage form has opened up new field for the research of Chinese medicine preparation.The SMEDDS basic feature is under ambient temperature (being often referred to 37 ℃ of body temperature) condition, run into gastro-intestinal Fluid after, can be at spontaneous formation O/W type microemulsion under the gastrointestinal wriggling, enter in the body after, in case disperse in their body behavior consistent with microemulsion.
Compare with common Emulsion or microemulsion, the advantage of SMEDDS mainly contains: can be under the gastrointestinal tract condition spontaneous formation microemulsion; Slightly solubility or fat-soluble medicine had higher solubilising power; Can filtration sterilization, can be used as intravenous administration formulation; Higher physical stability is arranged; Can be filled in hard capsule or the soft capsule, preparation technology is simple, carries out commercial production easily.In addition, can also add appropriate excipients in self-microemulsion, prepare corresponding solid self-micro emulsion formulation, these solid self-micro emulsion formulations can improve the dissolution of medicine, and help improving bioavailability.
SMEDDS compares with capsule with traditional tablet, but the medicine fast Absorption.For good self-emulsifying microemulsion system, can form the little emulsion droplet that includes dissolved substance when contacting with gastric juice, therefore, the medicine in the microemulsion emulsion droplet has bigger interfacial area, and medicine can keep dissolved state in intestinal, thereby better disperses permeate through cell membranes.
In the research of the numerous self microemulsifying preparations of pharmaceutical field, a good appetite suddenly appearing in a serious disease prescription body have related outside, less to the research of Chinese medicine active component.Because Chinese medicinal components is formed complicated, even same classification component also contains the number of chemical composition, so the research of Chinese medicine active component self-microemulsion is comparatively difficult.So the research report of ganoderma lucidum triterpene component self-micro emulsion formulation is not arranged at present as yet.
Summary of the invention
The object of the present invention is to provide a kind of self-mciro emulsifying nano composition (self-micro emulsion formulation) of ganodenic acid extract, this nano-composition is from the characteristics and the antitumor action of ganodenic acid extract, with water-insoluble drug Ganoderma total triterpenes extract preparation becoming self microemulsifying preparation, can improve the dissolution of medicine, promote drug absorption, and help improving bioavailability; Simultaneously medicine has bigger interfacial area, and medicine can keep dissolved state in intestinal, thereby better disperses permeate through cell membranes, and then improves the drug effect of medicine.The Ganoderma triterpenoids self-microemulsion drug-supplying system of the present invention's preparation is compared with present conventional suspensoid, and the anti-tumor in vivo effect strengthens.
Another object of the present invention is to provide the preparation method of the self-mciro emulsifying nano composition of this ganodenic acid extract.
Technical scheme of the present invention is, a kind of self-mciro emulsifying nano composition of ganodenic acid extract (self-micro emulsion formulation), with ganodenic acid extract as crude drug, the mixture that adopts surfactant, cosurfactant and oil phase composition is as pharmaceutical carrier, it is characterized in that each ingredients weight parts is as follows:
10 parts of ganodenic acid extracts, 50～400 parts in surfactant, 100～800 parts of cosurfactants, 15～600 parts of oil phases.
The optimized proportion of each ingredients weight parts is:
10 parts of ganodenic acid extracts, 100～300 parts in surfactant, 200～600 parts of cosurfactants, 40～400 parts of oil phases.
The ratio of more optimizing of each ingredients weight parts is:
10 parts of ganodenic acid extracts, 150～200 parts in surfactant, 300～500 parts of cosurfactants, 100～200 parts of oil phases.
Above-mentioned Ganoderma total triterpenes extract is that Ganoderma sporophore is passed through supercritical CO
2The method of extraction extraction obtains.(referring to: Song Shihua, Jia Xiaobin, Chen Yan, etc.Supercritical CO
2Total triterpenes component [J] in the extracting ganoderma sporophore. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2008,33 (17): 2104-2107.)
Above-mentioned surfactant can be selected from one of following or their combination: the fatty acid Pyrusussuriensis is smooth, Polysorbate, polyoxyethylene 40 fatty acid esters, polyoxyethylene aliphatic alcohol ether, polyoxyethylene-polyoxypropylene copolymer, lecithin, or OP emulsifying agent.
Above-mentioned fatty acid Pyrusussuriensis is smooth to be selected from one of following or their combination: span 20, span 40, sorbester p18, sorbester p38, sorbester p17, or sorbester p37.
Above-mentioned Polysorbate is selected from one of following or their combination: polysorbate 20 (polysorbas20), polysorbate 40, polysorbate 60, polysorbate 65, polyoxyethylene sorbitan monoleate, or polysorbate 85.
Above-mentioned polyoxyethylene aliphatic alcohol ether is selected from one of following or their combination: pool, Kaifeng 30, pool, Kaifeng 35, cetomacrogol (Cetomacrogol), paregal O (PerogolO) or Cremophore EL (polyoxyethylene castor oil glycerin ether)
Above-mentioned polyoxyethylene-polyoxypropylene copolymer is selected from one of following or their combination: Poloxamer 124 (poloxamer 124), Poloxamer 188 (poloxamer 1 88), Poloxamer237 (poloxamer 237), Poloxamer338 (poloxamer 338), or Poloxamer407 (poloxamer 407).
Above-mentioned cosurfactant can be selected from one of following or their compositions: ethanol, isopropyl alcohol, 1,2-propylene glycol, glycerol, n-butyl alcohol, n-octyl alcohol, n-heptanol, Liquid Macrogol, or PEG400.
Above-mentioned oil phase can be selected from one of following or their compositions: oleic acid, ethyl oleate, Oleum Arachidis hypogaeae semen, Oleum Glycines, Oleum Ricini, olive oil, Ethyl linoleate, isopropyl myristate, propyleneglycoles list caprylate, the two caprylates of propyleneglycoles, or Monooctamoin.
The preparation method of the self-mciro emulsifying nano composition of ganodenic acid extract of the present invention (Ganoderma triterpenoids self microemulsifying preparation), step is as follows:
(1). get ganodenic acid extract in proportion and be put in the container;
(2). add surfactant, cosurfactant again, the magnetic agitation mixing makes medicine dissolution;
(3). add oil phase again, the magnetic agitation mixing promptly gets the Ganoderma triterpenoids self-micro emulsion formulation.
It is can form with magnetic stirrer that the present invention prepares the Ganoderma triterpenoids microemulsion.
Take for the ease of the patient, the Ganoderma triterpenoids oral preparation composition of self-emulsifying microemulsion of the present invention can be adopted method fill well known in the art in capsule, obtain capsule.
Or, adopt method well known in the art to be prepared into tablet, soft capsule, oral liquid, granule etc. with the Ganoderma triterpenoids oral preparation composition of self-emulsifying microemulsion of the present invention and pharmaceutically acceptable carrier.
Compare with inferior Emulsion (particle diameter is generally at 0.1～10 μ m) with conventional Emulsion, self-microemulsion, microemulsion particle diameter littler (100nm is following) belong to thermodynamic stable system; Owing to there is a large amount of water (O/W), be difficult to make solid (as soft capsule) preparation in the microemulsion prescription, the administration of clinical general employing liquid type is given to pack, transport, store, carry etc. and is brought inconvenience; Self-microemulsion then promptly can be made into liquid dosage form, again can fill maybe can charge in soft capsule to make solid preparation in the hard capsule and use.And self-micro emulsion formulation is easy to preparation, does not need special installation to get final product mass production, good stability and easily industrialization, therefore has good industrial prospect.
The anti-tumor in vivo zoopery shows: the Ganoderma triterpenoids microemulsion can medicament curative effect enhancement, improves antitumous effect.
The beneficial effect of Ganoderma triterpenoids self microemulsifying preparation that the present invention is prepared and preparation method thereof shows following several respects:
1, the formulation preparation method of the present invention's preparation is simple, and need not special installation can finish, and realizes industrialized great production easily.
2, the selected surfactant of the present invention have advantages such as safe, nontoxic, nonirritant, and emulsifiability is good, find that by external emulsifying experiment back its emulsifying particle diameter is less, between 10～100nm, reach nanoscale, help absorbing, antitumous effect is better.
Description of drawings
Fig. 1 is the particle size distribution figure of the solution that forms of the Ganoderma triterpenoids self-emulsifying microemulsion of embodiment 1 preparation.
The specific embodiment
Below in conjunction with example the present invention is described in further detail, but should notices that scope of the present invention is not subjected to any restriction of these examples.
Embodiment 1
Prescription: Ganoderma total triterpenes extract 30mg, tween 20 1200mg, isopropyl alcohol 2400mg, oleic acid 1800mg.
Ganoderma total triterpenes extract, tween 20, isopropyl alcohol are put into cillin bottle, by the abundant mix homogeneously of magnetic agitation, treat that medicine dissolves fully after, add oleic acid, behind the magnetic agitation 10min, just can obtain the ganodenic acid extract self-emulsifying composition again.
Embodiment 2
Prescription: Ganoderma total triterpenes extract 100mg, Arlacel-20 1000mg, ethanol 6000mg, ethyl oleate 500mg.
Preparation method is with embodiment 1.
Embodiment 3
Prescription: Ganoderma total triterpenes extract 50mg, phospholipid-20 250mg, ethanol 500mg, isopropyl myristate 75mg.
Preparation method is with embodiment 1.
Embodiment 4
Prescription: Ganoderma total triterpenes extract 40mg, Cremophore EL 800mg, ethanol 1600mg, soybean oil 1200mg.
Preparation method is with embodiment 1.
Embodiment 5
Prescription: Ganoderma total triterpenes extract 80mg, Poloxamer 188 2400mg, 1,2-propylene glycol 4000mg, Ethyl linoleate 3200mg.
Preparation method is with embodiment 1.
The anti-tumor in vivo experiment of embodiment 6. ganodenic acid extract self-microemulsion
Select inoculation 7d, well-grown lotus Heps liver cancer mouse, the cervical vertebra dislocation is put to death, and aseptic extraction ascites becomes 2 * 10 with physiological saline solution by 1: 4 dilution proportion
7The tumor cell suspension of individual/mL, it is subcutaneous to be inoculated in the healthy mice right fore, every 0.2mL.Inoculate next day, be divided into 6 groups at random, be respectively: normal saline blank group by body weight; The cyclophosphamide positive controls; The high low dose group of ganodenic acid extract self-microemulsion (5.0g crude drug kg
-1D
-1, 2.5g crude drug kg
-1D
-1), the high low dose group of ganodenic acid extract suspension (5.0g crude drug kg
-1D
-1, 2.5g crude drug kg
-1D
-1).The cyclophosphamide positive controls is lumbar injection (20mgkg
-1D
-1), other group is for gastric infusion, is every day 1 time, continuously 7d.During this time, observe the situation such as general activity, fur, feces of mice every day.Put to death mice with cervical vertebra dislocation behind the 24h after the last administration and strip tumor tissue, cut open simultaneously and get mouse spleen, thymus, weigh, calculate tumour inhibiting rate, spleen index, thymus index, the results are shown in Table 1, table 2.
Tumour inhibiting rate (%)=(it is heavy that the average tumor of average tumor weight/matched group is organized in the 1-treatment) * 100%;
Heavy (the mg)/mice body weight (g) of spleen index=spleen;
Heavy (the mg)/mice body weight (g) of thymus index=thymus.
Experimental result shows, the Ganoderma triterpenoids self-microemulsion can suppress growth of tumor, the tumor weight of 2 dosage groups of its height and cyclophosphamide positive controls is starkly lower than the normal saline matched group, and Ganoderma self-microemulsion high and low dose group tumour inhibiting rate is respectively 52.34%, 37.66%.Ganoderma triterpenoids self-microemulsion group and suspension group compare, and tumour inhibiting rate has significance to improve (P＜0.05), and experimental result sees Table 1.
Table 1. Ganoderma triterpenoids self-microemulsion is to the inhibitory action of Heps mice with tumor (x ± S)
Annotate: compare with the normal saline group:
*P＜0.05
Compare with corresponding suspendible medicine group:
ΔP＜0.05
The spleen index of mice, thymus index and model normal saline matched group compare there was no significant difference after the administration, and immune organ spleen and thymus are not had influence; Suspendible medicine group and microemulsion group compare, and spleen index and thymus index be there was no significant difference also, and visible Ganoderma triterpenoids microemulsion does not have influence to immune organ spleen and thymus.Experimental result sees Table 2.
This experiment is an object of study with the Ganoderma triterpenoids self-microemulsion, and its antitumor action has been carried out exploratory study.Experimental result is tentatively pointed out: the Ganoderma triterpenoids self-microemulsion all has good inhibitory effect to the Heps mice with tumor.Its antitumor action and suspension relatively have the potentiation (P＜0.05) of significance.
Table 2 Ganoderma triterpenoids self-microemulsion is to the influence of Heps mice with tumor spleen and thymus (x ± S)
Annotate: compare with the normal saline matched group:
*P＜0.05
Embodiment 7, and is substantially the same manner as Example 1, but each ingredients weight parts is as follows: 10 parts of ganodenic acid extracts, surfactant 100, cosurfactant 200,40 parts of oil phases.
Described surfactant can be selected from one of following or their combination: the fatty acid Pyrusussuriensis is smooth, Polysorbate, polyoxyethylene 40 fatty acid esters, polyoxyethylene aliphatic alcohol ether, polyoxyethylene-polyoxypropylene copolymer, lecithin, or OP emulsifying agent;
Described cosurfactant can be selected from one of following or their compositions: ethanol, isopropyl alcohol, 1,2-propylene glycol, glycerol, n-butyl alcohol, n-octyl alcohol, n-heptanol, Liquid Macrogol, or PEG400;
Described oil phase can be selected from one of following or their compositions: oleic acid, ethyl oleate, Oleum Arachidis hypogaeae semen, Oleum Glycines, Oleum Ricini, olive oil, Ethyl linoleate, isopropyl myristate, propyleneglycoles list caprylate, the two caprylates of propyleneglycoles, or Monooctamoin.
Embodiment 8, and is substantially the same manner as Example 1, but each ingredients weight parts is as follows: 10 parts of ganodenic acid extracts, 300 parts in surfactant, 600 parts of cosurfactants, 400 parts of oil phases.
Embodiment 9, and is substantially the same manner as Example 1, but each ingredients weight parts is as follows: 10 parts of ganodenic acid extracts, 150 parts in surfactant, cosurfactant 300,100 parts of oil phases.
Polysorbate described in the surfactant is selected from one of following or their combination: polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polyoxyethylene sorbitan monoleate, or polysorbate 85;
Polyoxyethylene aliphatic alcohol ether described in the surfactant is selected from one of following or their combination: pool, Kaifeng 30, pool, Kaifeng 35, cetomacrogol, paregal O or polyoxyethylene castor oil glycerin ether;
Polyoxyethylene described in the surfactant-polyoxypropylene copolymer is selected from one of following or their combination: poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, or poloxamer 407.
Embodiment 10, and is substantially the same manner as Example 1, but each ingredients weight parts is as follows: 10 parts of ganodenic acid extracts, 200 parts in surfactant, 500 parts of cosurfactants, 200 parts of oil phases.
Claims (10)
1, a kind of self-mciro emulsifying nano composition of ganodenic acid extract, as crude drug, the mixture that adopts surfactant, cosurfactant and oil phase composition is characterized in that as pharmaceutical carrier each ingredients weight parts is as follows with ganodenic acid extract:
10 parts of ganodenic acid extracts, 50～400 parts in surfactant, 100～800 parts of cosurfactants, 15～600 parts of oil phases.
2, the self-mciro emulsifying nano composition of ganodenic acid extract according to claim 1 is characterized in that, the weight portion ratio of described each component is:
10 parts of ganodenic acid extracts, 100～300 parts in surfactant, 200～600 parts of cosurfactants, 40～400 parts of oil phases.
3, the self-mciro emulsifying nano composition of ganodenic acid extract according to claim 2 is characterized in that, the weight portion ratio of described each component is:
10 parts of ganodenic acid extracts, 150～200 parts in surfactant, 300～500 parts of cosurfactants, 100～200 parts of oil phases.
4, the self-mciro emulsifying nano composition of ganodenic acid extract according to claim 1 is characterized in that, described Ganoderma total triterpenes extract is meant: Ganoderma sporophore is passed through supercritical CO
2The Ganoderma total triterpenes extract that the method for extraction extraction obtains.
5, according to the self-mciro emulsifying nano composition of claim 1 or 2 or 3 or 4 described ganodenic acid extracts, it is characterized in that,
Described surfactant is selected from one of following or their combination: the fatty acid Pyrusussuriensis is smooth, Polysorbate, polyoxyethylene 40 fatty acid esters, polyoxyethylene aliphatic alcohol ether, polyoxyethylene-polyoxypropylene copolymer, lecithin, or OP emulsifying agent;
Described cosurfactant is selected from one of following or their compositions: ethanol, isopropyl alcohol, 1,2-propylene glycol, glycerol, n-butyl alcohol, n-octyl alcohol, n-heptanol, Liquid Macrogol, or PEG400;
Described oil phase is selected from one of following or their compositions: oleic acid, ethyl oleate, Oleum Arachidis hypogaeae semen, Oleum Glycines, Oleum Ricini, olive oil, Ethyl linoleate, isopropyl myristate, propyleneglycoles list caprylate, the two caprylates of propyleneglycoles, or Monooctamoin.
6, the self-mciro emulsifying nano composition of ganodenic acid extract according to claim 5 is characterized in that,
Fatty acid Pyrusussuriensis described in the surfactant is smooth to be selected from one of following or their combination: span 20, span 40, sorbester p18, sorbester p38, sorbester p17, or sorbester p37;
Polysorbate described in the surfactant is selected from one of following or their combination: polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polyoxyethylene sorbitan monoleate, or polysorbate 85;
Polyoxyethylene aliphatic alcohol ether described in the surfactant is selected from one of following or their combination: pool, Kaifeng 30, pool, Kaifeng 35, cetomacrogol, paregal O or polyoxyethylene castor oil glycerin ether;
Polyoxyethylene described in the surfactant-polyoxypropylene copolymer is selected from one of following or their combination: poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, or poloxamer 407.
7, the preparation method of the self-mciro emulsifying nano composition of the described ganodenic acid extract of a kind of claim 1 is characterized in that step is as follows:
(1). get ganodenic acid extract in proportion and be put in the container;
(2). add surfactant, cosurfactant again, the magnetic agitation mixing makes medicine dissolution;
(3). add oil phase again, the magnetic agitation mixing promptly gets the Ganoderma triterpenoids self-micro emulsion formulation.
8, the preparation method of the self-mciro emulsifying nano composition of ganodenic acid extract according to claim 7 is characterized in that, the weight portion ratio of described each component is:
10 parts of ganodenic acid extracts, 50～400 parts in surfactant, 100～800 parts of cosurfactants, 15～600 parts of oil phases;
Described surfactant is selected from one of following or their combination: the fatty acid Pyrusussuriensis is smooth, Polysorbate, polyoxyethylene 40 fatty acid esters, polyoxyethylene aliphatic alcohol ether, polyoxyethylene-polyoxypropylene copolymer, lecithin, or OP emulsifying agent;
Described cosurfactant is selected from one of following or their compositions: ethanol, isopropyl alcohol, 1,2-propylene glycol, glycerol, n-butyl alcohol, n-octyl alcohol, n-heptanol, Liquid Macrogol, or PEG400;
Described oil phase is selected from one of following or their compositions: oleic acid, ethyl oleate, Oleum Arachidis hypogaeae semen, Oleum Glycines, Oleum Ricini, olive oil, Ethyl linoleate, isopropyl myristate, propyleneglycoles list caprylate, the two caprylates of propyleneglycoles, or Monooctamoin.
9, according to the preparation method of the self-mciro emulsifying nano composition of claim 7 or 8 described ganodenic acid extracts, it is characterized in that the weight portion ratio of described each component is:
10 parts of ganodenic acid extracts, 100～300 parts in surfactant, 200～600 parts of cosurfactants, 40～400 parts of oil phases;
Described fatty acid Pyrusussuriensis is smooth to be selected from one of following or their combination: span 20, span 40, sorbester p18, sorbester p38, sorbester p17, or sorbester p37;
Described Polysorbate is selected from one of following or their combination: polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polyoxyethylene sorbitan monoleate, or polysorbate 85;
Described polyoxyethylene aliphatic alcohol ether is selected from one of following or their combination: pool, Kaifeng 30, pool, Kaifeng 35, cetomacrogol, paregal O or polyoxyethylene castor oil glycerin ether;
Described polyoxyethylene-polyoxypropylene copolymer is selected from one of following or their combination: poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, or poloxamer 407.
10, according to the preparation method of the self-mciro emulsifying nano composition of claim 7 or 9 described ganodenic acid extracts, it is characterized in that the weight portion ratio of described each component is:
10 parts of ganodenic acid extracts, 150～200 parts in surfactant, 300～500 parts of cosurfactants, 100～200 parts of oil phases.
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