CN100349565C - Curcumenol solid lipid nano-particle and its preparation method - Google Patents
Curcumenol solid lipid nano-particle and its preparation method Download PDFInfo
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- CN100349565C CN100349565C CNB2005100946300A CN200510094630A CN100349565C CN 100349565 C CN100349565 C CN 100349565C CN B2005100946300 A CNB2005100946300 A CN B2005100946300A CN 200510094630 A CN200510094630 A CN 200510094630A CN 100349565 C CN100349565 C CN 100349565C
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- QRMPRVXWPCLVNI-UHFFFAOYSA-N Curcumenol Natural products C1C(=C)C2CCC(C)C22CC(C(C)C)C1(O)O2 QRMPRVXWPCLVNI-UHFFFAOYSA-N 0.000 title claims abstract description 80
- ISFMXVMWEWLJGJ-NZBPQXDJSA-N curcumenol Chemical compound CC1=C[C@](O2)(O)C(=C(C)C)C[C@@]22[C@@H](C)CC[C@H]21 ISFMXVMWEWLJGJ-NZBPQXDJSA-N 0.000 title claims abstract description 80
- 239000002047 solid lipid nanoparticle Substances 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000004094 surface-active agent Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- 239000000725 suspension Substances 0.000 claims description 21
- 208000035126 Facies Diseases 0.000 claims description 20
- 239000002245 particle Substances 0.000 claims description 17
- 239000011159 matrix material Substances 0.000 claims description 16
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 claims description 12
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- 238000004108 freeze drying Methods 0.000 claims description 11
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 10
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 10
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 10
- 229940083466 soybean lecithin Drugs 0.000 claims description 10
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- 150000003904 phospholipids Chemical class 0.000 claims description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
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- VMPHSYLJUKZBJJ-UHFFFAOYSA-N trilaurin Chemical compound CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 claims description 4
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 3
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- 229920001503 Glucan Polymers 0.000 claims description 3
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 3
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 claims description 3
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 claims description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 3
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- 238000001694 spray drying Methods 0.000 claims description 3
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 claims description 3
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 2
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 244000147568 Laurus nobilis Species 0.000 claims description 2
- 235000017858 Laurus nobilis Nutrition 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 235000005212 Terminalia tomentosa Nutrition 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 2
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 2
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 3
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 3
- 235000012141 vanillin Nutrition 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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Abstract
The present invention relates to the field of medicinal preparations, and discloses a curcumenol solid lipid nanoparticle and a preparation method thereof. The curcumenol solid lipid nanoparticle contains 1 share of curcumenol, 3 to 10 shares of phosphatide, 5 to 100 shares of lipid material, 10 to 200 of surface active agent and 10 to 400 shares of excipient. The curcumenol solid lipid nanoparticle enhances the degree of dispersedness of the medicine in carrier materials, improves the dissolution of the medicine, enhances the bioavailability, changes the intracorporal process of the medicine, enhances the target character to focus tissues, increases the therapeutic index of the medicine, and reduces a medicine dosage and toxic side effect.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to solid lipid nanoparticle of a kind of Chinese medicine curcumenol and preparation method thereof.
Background technology
Curcumenol (Curcmol) has another name called Rhizoma Curcumae Longae epoxy alcohol, for the sesquiterpenoids that extracts, from the seventies, is mainly used in the treatment of cervical cancer from Rhizoma Curcumae volatile oil, and has obtained tangible curative effect.In recent years, pharmacy worker has carried out pharmaceutical research widely to curcumenol, finds that it has direct inhibition and destruction to the mice ehrlich carcinoma.Curcumenol also has the effect of antibiotic and antiviral etc. except being used for the treatment of tumor.From in appearance, curcumenol is colourless acicular crystal.Curcumenol is soluble in ether, chloroform, is dissolved in ethanol, is slightly soluble in petroleum ether, and is water-soluble hardly, and the dissolubility in water only is 0.3%.(progress of curcumenol such as Deng Rong " Liaoning medicine and clinical " the 4th the 1st phase of volume of calendar year 2001).Because it is insoluble in water, limited in clinical being extensive use of.Have report with curcumenol with the beta cyclodextrin enclose increasing its dissolubility (beta cyclodextrin such as Huang Guihua is inquired into the 12nd the 5th phase of volume of " northwest pharmaceutical journal " October in 1997 to the clathration of curcumenol), but the not preparation of curcumenol listing at present.
Solid lipid nanoparticle is a kind of new drug carrier, by medicine is wrapped up or is embedded in the lipoid nuclear, makes the solid micelle drug-supplying system that particle diameter is about 50～1000nm.It has advantages such as targeting, controlled release, raising medicine stability, toxicity be little, is a kind of extremely promising novel drug-supplying system.Because it has certain technical difficulty, general occur easily under study for action that drug loading is little, prominent to be released and unfavorable factor that envelop rate is low etc., the influence factor who causes these bad results mainly is the concentration of character, medicine and adjuvant of pharmaceutical properties, matrix material and preparation technology etc.Because different medicines has different physicochemical properties, so the technical scheme that different pharmaceutical is fit to when being prepared into solid lipid nanoparticle is also different.
Curcumenol belongs to natural drug, and fusing point is 147-142 ℃, has the hydrogenation compounds difficult to understand of hemiketal.Do not see the report that Curcumenol solid lipid nano-particle is arranged in the prior art, do not have the report of the solid lipid nanoparticle of the physicochemical property medicine similar or close yet to it.
Summary of the invention
The invention discloses a kind of Chinese medicine Curcumenol solid lipid nano-particle and preparation method thereof.The curcumenol bag is stated from the solid lipid nano-particles, is prepared into nano level curcumenol granular preparation, reduce the diameter of drug particles, increased particulate specific surface area, thereby improved the bioavailability of insoluble drug curcumenol greatly.Realize the passive targeting of the drug-supplying system of nanoparticle by controlling nanometer particle size, increase the selectivity of curcumenol, better bring into play curative effect the lesions position treatment.
In early-stage Study, the inventor once attempted the consumption of various matrix materials, find when used matrix material identical with medication amount, no matter how other adjuvants change, the nanoparticle envelop rate that the result makes is very low, has only about 20%.If increase the amount of matrix material, in 1 part of medicine, calculate by weight, drop into the matrix material more than 150 parts, even after finding to increase the pressure of high pressure homogenize, prepared nanoparticle particle diameter is also very big, can reach about 350nm; The result of optimizing prescriptions shows simultaneously; consumption as emulsifying agent is very few, can not form stable Emulsion, and is excessive as the emulsifying agent consumption; the nanoparticle suspension foam that then makes much also has a thickness, must consider the too high toxicity problem that brings of emulsifying agent consumption in addition.Therefore in 1 part the medicine, calculate by weight, drop into 10～200 parts of emulsifying agents; In the process of selecting the phospholipid amount for use, find that consumption is too low, in 1 part medicine, calculate by weight, only drop into 1 part of phospholipid, the nanoparticle stability that the result makes is very poor, at room temperature leaving standstill the phenomenon that particle aggregation is just arranged about 2h occurs, excessive as the phospholipid consumption, prepared nanoparticle system is thickness relatively, has also brought very high cost to suitability for industrialized production simultaneously.By the test of many times of multiple adjuvant, multiple amount ratio, formed the present invention program of suitable Curcumenol solid lipid nano-particle at last.
Curcumenol solid lipid nano-particle of the present invention is realized by following scheme:
Curcumenol solid lipid nano-particle of the present invention, contain following component and weight ratio:
1 part of curcumenol
Phosphatidase 13～100 part
5～100 parts of matrix materials
10～200 parts in surfactant
10～400 parts of excipient.
The preferred weight ratio of above-mentioned each component is:
1 part of curcumenol
0～70 part of phosphatidase 11
10～80 parts of matrix materials
20～120 parts in surfactant
30～300 parts of excipient.
Most preferred weight ratio is:
1 part of curcumenol
0～50 part of phosphatidase 13
40～50 parts of matrix materials
60～80 parts in surfactant
80～200 parts of excipient.
Phospholipid preferably soya lecithin, soyabean cephalin, Semen sojae atricolor lipositol, two Laurel phosphatidyl cholines, two inferior phosphatidyl cholines, distearoyl phosphatidylcholine, dipalmitoyl phosphatidyl choline or two myristoyl phosphatidylcholines in the above-mentioned prescription; The preferred stearic acid of matrix material, glyceryl monostearate, trilaurin, glycerol trioleate, glyceryl tristearate, microcrystalline wax or whale ester are cured; In the preferred poloxamer 188 of surfactant, polyoxyethylene hydrogenated Oleum Ricini, polysorbate60, Myrij 51 and the tween 80 one or more, in the preferred mannitol of excipient, glucose, lactose, glucosan, the trehalose one or more.
More preferably: phospholipid is soybean lecithin; Matrix material is a stearic acid; Surfactant is a poloxamer 188; Excipient is a mannitol.
The preparation method of Curcumenol solid lipid nano-particle of the present invention may further comprise the steps:
Curcumenol, phospholipid, matrix material are dissolved in appropriate amount of organic constitute organic facies; Surfactant is dissolved in an amount of water constitutes water; Organic facies and water are heated to uniform temp respectively, under stirring condition organic facies are injected aqueous phase, form transparent system; Organic solvent is removed in this transparent system decompression; mix after concentrated in 0～2 ℃ aqueous phase and stir cooling; handle through high pressure homogenizer again; get the solid lipid nanoparticle suspension; then will be in the nanoparticle suspension that obtains add excipient dissolving after-filtration, the filtrate spray drying or after lyophilization promptly.
In the above-mentioned preparation method, more preferably condition is: organic solution is acetone, ethanol or isopropyl alcohol; Organic facies and water volume ratio are 1: 3～1: 4.
Excipient among the present invention also claims protective agent, is freeze drying protectant in lyophilizing.The inventor finds that the envelop rate that records after the lyophilization improves slightly than the envelop rate that records, and the stability of product also improves when suspension.Therefore, preferred manufacturing procedure of the present invention is to select freeze-drying method for use at drying steps, and Zhi Bei product quality is more stable like this.
The preparation method of solid lipid nanoparticle was exactly under the temperature that is higher than the matrix material fusing point in the past; organic facies is distributed to synthermal aqueous phase by approach such as high-speed stirred; be stirred to and form transparent system; the rotary evaporation that reduces pressure is again removed organic solvent and is concentrated back cooling rapidly; form the solid lipid nanoparticle suspension; but the solid lipid nanoparticle size that makes like this is heterogeneity very, and stability is also very poor, at room temperature places to begin to occur particle aggregation and deposited phenomenon easily.
The present invention adopts emulsifying-solvent evaporates to prepare the Curcumenol solid lipid nano-particle lyophilized powder in conjunction with the high pressure homogenize and the vacuum freezing drying method that are easy to suitability for industrialized production, particle diameter and envelop rate by prescription and process conditions control nanoparticle obtain stay-in-grade preparation.The prepared Curcumenol solid lipid nano-particle particle diameter of the present invention is at 100～220nm, and envelop rate is greater than 70%.After the prepared Curcumenol solid lipid nano-particle lyophilized powder of the present invention was at room temperature stored 6 months, the particle diameter that records behind the water redispersion increased a little, and at 180～260nm place, envelop rate is constant substantially.Illustrate that Curcumenol solid lipid nano-particle lyophilized powder stability that the present invention makes better.
As follows to the experiment of evaluation of indexes such as the particle diameter of Curcumenol solid lipid nano-particle of the present invention and envelop rate:
1, takes transmission electron microscope (TEM) photo of Curcumenol solid lipid nano-particle
Curcumenol nanoparticle suspension of the present invention is suitably diluted with distilled water; dropping is on the copper mesh that covers carbon film; dye with 2.0% Sodium phosphotungstate negative staining liquid; take transmission electron microscope photo with the JEM-2010 transmission electron microscope; the results are shown in Figure 1, Curcumenol solid lipid nano-particle of the present invention as can be seen from Figure 1 is big or small homogeneous, a roundness spheroidal particle preferably.
2, measure the size and the distribution thereof of Curcumenol solid lipid nano-particle
Curcumenol nanoparticle suspension of the present invention is suitably diluted with distilled water, measure the size and the distribution thereof of nanoparticle with Zetasizer 3000HS laser particle size analyzer.The results are shown in Figure 2, Fig. 2 shows the most of particle diameter of Curcumenol solid lipid nano-particle that the present invention makes about 150nm, and polydispersity coefficient is 0.42, and particle size distribution range is narrower.
3, measure the envelop rate of Curcumenol solid lipid nano-particle
Adopt the Superfreezing centrifugation method to separate Curcumenol solid lipid nano-particle and free drug, measure its envelop rate.Drawing 1ml solid lipid nanoparticle suspension inserts in the 1.5ml centrifuge tube; under 4 ℃ of conditions with 20000 rev/mins of ultracentrifugation 30min; get and add the vanillin sulfuric acid solution after supernatant 0.5ml dilutes several 50 times with dehydrated alcohol and (get vanillin 0.2g; add ethanol 1ml; make dissolving; add cold sulfuric acid solution (1 → 2) 100ml again, shake up, be i.e.) colour developing.20～25 ℃ place 1h after in 520nm place its absorption value of mensuration; Other draws 1ml solid lipid nanoparticle suspension and adds anhydrous alcohol solution, gets to add the colour developing of vanillin sulfuric acid solution after 0.5ml dilutes several 50 times with dehydrated alcohol.20～25 ℃ place 1h after in 520nm place its absorption value of mensuration.According to envelop rate computing formula computational envelope rate:
EN(％)＝(C
0-C)/C
0×100％
Wherein: EN represents envelop rate; C and C
0Represent the free drug content that is not wrapped in the supernatant and the total dose in the nanoparticle suspension respectively.
The entrapment efficiency determination result of Curcumenol solid lipid nano-particle is 70%～85%.
The dissolubility of curcumenol in water is very little, the present invention makes curcumenol the solid lipid nanoparticle with suitable particle diameter, not only improve the degree of scatter of medicine at carrier material, improve the stripping of medicine, improve bioavailability, and can change the physiological disposition of medicine, increase its targeting lesion tissue, improve the therapeutic index of medicine, reduce dosage and toxic and side effects.Solid lipid nanoparticle lyophilized powder of the present invention has protective effect to medicine, can solve liposome preferably, the problem that preparation of Chinese medicine such as microemulsion easily leak.Curcumenol nano-granule freeze-dried powder preparation of the present invention is stated from the insoluble drug curcumenol in the solid lipid nanoparticle by above-mentioned method bag, and the drug effect of curcumenol can be brought into play on nanometer level.
The Curcumenol solid lipid nano-particle that the present invention makes, directly fill is in capsule or cillin bottle, be used for oral or injection, by oral route is applied to clinical after also can adding the mixed fill of other pharmaceutical necessities again, also can make injectable powder with suitable adjuvant, facing with the suitable solvent of preceding usefulness, be applied to clinical by the intravenous injection approach with Curcumenol solid lipid nano-particle lyophilized powder redispersion.Curcumenol solid lipid nano-particle lyophilized powder per unit dosage drug content is generally 0.03-1mg.
Be described more specifically the present invention by the following example.But these embodiment should not be construed as the restriction to any aspect of the present invention.
Description of drawings
The transmission electron microscope of Fig. 1, Curcumenol solid lipid nano-particle (TEM) photo
The size of Curcumenol solid lipid nano-particle is represented in the particle diameter of Fig. 2, Curcumenol solid lipid nano-particle and distribution thereof, abscissa, and vertical coordinate is represented the percentage composition of a certain grain diameter nano grain.
The specific embodiment
Embodiment 1
10mg curcumenol and 50mg stearic acid are dissolved in 8ml acetone, and the 30mg soybean lecithin is with the 2ml dissolve with ethanol, and two parts mix, and constitute organic facies.100mg Poloxamer188 is dissolved in the 40ml distilled water, constitutes water.Organic facies and water are heated to 75 ℃ respectively, under 1500 rev/mins stirring condition organic facies are slowly injected aqueous phase with No. 6 syringe needles, form translucent system; This translucent system is removed organic solvent and is concentrated into 2/5 volume with the Rotary Evaporators reduction vaporization.System after concentrating is mixed fast in 0 ℃ aqueous phase and is stirred cooling 2 hours, is 800Bar through high pressure homogenizer in operating pressure again, handles 3 circulations under the condition of ice bath, gets the solid lipid nanoparticle suspension.After adding excipient mannitol 100mg dissolving in the nanoparticle suspension that obtains, remove macroparticle with the filtering with microporous membrane of 0.45 μ m, filtrate gets lyophilized powder through lyophilization after 48 hours under-40 ℃ of conditions.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 104.3nm, and envelop rate is 70.11%.
Embodiment 2
10mg curcumenol, 900mg glyceryl monostearate are dissolved in 8ml acetone, and the 800mg dipalmitoyl phosphatidyl choline is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.2000mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1000Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds the excipient trehalose is 2g, uses the spray drying method drying.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 216.2nm, and envelop rate is 72.56%.
Embodiment 3
10mg curcumenol, 100mg glycerol trioleate are dissolved in 8ml acetone, and the 100mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.200mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1000Bar, and the amount that suspension adds the excipient glucose is 300mg.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 123.4nm, and envelop rate is 73.64%.
Embodiment 4
10mg curcumenol, 800mg stearic acid are dissolved in 8ml acetone, and the 600mg dipalmitoyl phosphatidyl choline is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.1200mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1200Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds excipient mannitol is 2.2g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 172.4nm, and envelop rate is 80.76%.
10mg curcumenol, 400mg glyceryl monostearate are dissolved in 8ml acetone, and the 300mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.600mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1000Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds excipient mannitol is 1g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 141.4nm, and envelop rate is 81.64%.
Embodiment 6
10mg curcumenol, 500mg stearic acid are dissolved in 8ml acetone, and the 500mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.The 800mg polyoxyethylene hydrogenated Oleum Ricini is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1200Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds excipient mannitol is 1.5g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 166.7nm, and envelop rate is 83.45%.
Embodiment 7
10mg curcumenol, 420mg stearic acid are dissolved in 8ml acetone, and the 450mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.800mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1200Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds the excipient glucosan is 1g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 156.3nm, and envelop rate is 82.15%.
Embodiment 8
10mg curcumenol, 440mg stearic acid are dissolved in 8ml acetone, and the 350mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.650mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with example 1, and different is to change the high pressure homogenize operating pressure into 1200Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds excipient mannitol is 1.5g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 152.2nm, and envelop rate is 82.36%.
10mg curcumenol, 470mg stearic acid are dissolved in 8ml acetone, and the 420mg soybean lecithin is dissolved in 2ml ethanol, and two parts mix, and constitutes organic facies.720mg Poloxamer 188 is dissolved in the 40ml distilled water, constitutes water.Preparation technology is with embodiment 1, and different is to change the high pressure homogenize operating pressure into 1000Bar, and translucent system is concentrated into 1/2 original volume, and the amount that suspension adds excipient mannitol is 1g.
Detect: the mean diameter of Curcumenol solid lipid nano-particle is 158.4nm, and envelop rate is 83.09%.
Claims (6)
1, a kind of Curcumenol solid lipid nano-particle is characterized in that containing following component and weight ratio:
1 part of curcumenol
0～50 part of phosphatidase 13
40～50 parts of matrix materials
60～80 parts in surfactant
80～200 parts of freeze drying protectants,
Particle size range 100～220nm.
2, the Curcumenol solid lipid nano-particle of claim 1, wherein phospholipid is selected from soybean lecithin, soyabean cephalin, Semen sojae atricolor lipositol, two Laurel phosphatidyl cholines, two inferior phosphatidyl cholines, distearoyl phosphatidylcholine, dipalmitoyl phosphatidyl choline or two myristoyl phosphatidylcholines; It is cured that wherein matrix material is selected from stearic acid, glyceryl monostearate, trilaurin, glycerol trioleate, glyceryl tristearate, microcrystalline wax or whale ester; Wherein surfactant is selected from one or more in poloxamer 188, polyoxyethylene hydrogenated Oleum Ricini, polysorbate60, Myrij 51 and the tween 80, and freeze drying protectant is selected from one or more in mannitol, glucose, lactose, glucosan, the trehalose.
3, the Curcumenol solid lipid nano-particle of claim 1, wherein phospholipid is soybean lecithin; Matrix material is a stearic acid; Surfactant is a poloxamer 188, and freeze drying protectant is a mannitol.
4, the preparation method of each Curcumenol solid lipid nano-particle in the claim 1 to 3 may further comprise the steps:
Curcumenol, phospholipid, matrix material are dissolved in organic solvent constitute organic facies; With surfactant formation water soluble in water; Organic facies and water are heated to uniform temp respectively, under stirring condition organic facies are injected aqueous phase, form transparent system; Organic solvent is removed in this transparent system decompression, is mixed in 0～2 ℃ aqueous phase after concentrated and stir cooling, handle through high pressure homogenizer again, the solid lipid nanoparticle suspension, add the freeze drying protectant dissolving, filter, after filtrate spray drying or the lyophilization promptly.
5, the preparation method of claim 4, wherein organic solvent is acetone, ethanol or isopropyl alcohol; Organic facies and water volume ratio are 1: 3～1: 4.
6, the preparation method of claim 5, wherein drying is lyophilization.
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| CN104940167B (en) * | 2015-06-05 | 2018-01-23 | 厦门大学 | A kind of preparation method for loading berberine phosphatide composite nano particle |
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| CN106344508B (en) * | 2016-10-11 | 2019-08-09 | 辽宁大学 | A kind of rcumenol nano suspension and its preparation method and application |
| CN110051648A (en) * | 2018-01-19 | 2019-07-26 | 深圳大学 | A method of improving liposome nanometer carrier drug carrying ability |
| CN113082064B (en) * | 2021-04-23 | 2022-04-29 | 青岛科技大学 | Folium Platycladi gel absorbent for treating alopecia areata, preparation method thereof and external patch for treating alopecia areata |
| CN114711288A (en) * | 2022-03-01 | 2022-07-08 | 珠海科技学院 | Cinnamyl aldehyde solid lipid nanoparticle with high stability and preparation method thereof |
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