CN102961346A - Tamibarotene nano-liposome carrier and preparation method thereof - Google Patents
Tamibarotene nano-liposome carrier and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a tamibarotene nano-liposome carrier which comprises 0.05-10wt% of tamibarotene, 1-60wt% of solid lipid material, 0.5-30wt% of liquid lipid, 1-10wt% of lipid soluble emulsifier, 0.05-10wt% of water soluble emulsifier, 0 or 1-10wt% of freeze-drying protective agent and the balance of water for injection. A preparation method of the tamibarotene nano-liposome carrier is a fusing-emulsifying-low temperature setting method. The prepared tamibarotene nano-liposome carrier has a particle size within 100-200nm and is used for intravenous injection; and compared with the oral dosage form, the tamibarotene nano-liposome carrier has the advantages of decreasing the administration dosage, having slow release characteristic in vivo, prolonging the time of the drug in the blood and improving the bioavailability.
Description
Technical field
The present invention relates to Tamibarotene nano-lipid carrier and preparation method thereof, belong to field of pharmaceutical preparations.
Background technology
Tamibarotene (tamibarotene), chemical name 4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-yl) carbamyl] benzoic acid, the new selective retinoic acid α receptor promoter of Nippon Shinyaku Co., Ltd. (JP) Tokyo To, Japan (Nippon Shinyaku) exploitation, this medicine is external can successfully induce promyelocytic leukemia (promyelocytic leukemia, PML) cell differentiation and maturation, prevents PML propagation; In the test, anti-tumor activity and toleration have preferably been shown in vivo.Tamibarotene causes acute promyelocytic leukemia (Acute promyelocytic leukemia, APL) cell differentiation and dead external effectiveness to surpass approximately 10 times of all-trans-retinoic acids (ATRA) in addition.Tamibarotene in June, 2005 Japanese Initial Public Offering (trade name: Amnolake), the clinical treatment that is mainly used in APL relapsed or stubborn sexually transmitted disease (STD) example.The chemical structural formula of Tamibarotene is as follows:
Tamibarotene is white crystalline powder, is soluble in oxolane and dichloromethane, and is almost insoluble in water, also indissoluble or substantially insoluble in various buffer.Because its poorly water-soluble, oral absorption is poor, and bioavailability is low, thereby has limited its clinical practice.Tamibarotene mainly contains the Tablet and Capsula listing at present, but the bioavailability of Tamibarotene sheet lower (about 50%), because Tamibarotene water solublity extreme difference, there is not at present injection to come out, therefore, improve the dissolubility of insoluble drug, promote the absorption of medicine, the bioavailability that improves medicine is the difficult problem that the pharmaceutics field demands urgently capturing.
Novel nano carrier (such as liposome, nanoparticle etc.) demonstrates unique advantage aspect addressing the above problem: increase drug absorption, control drug release, change drug distribution.
Reported in literature lipid-based nano-carrier, liposome for example, solid lipid nanoparticle (solid lipid nanopaticles, SLN) and nano-lipid carrier (nanostructructured lipid carriers, NLC) etc., can significantly improve the delivery efficiency of the non-oral administration of hydrophobic drug, yet, liposome and SLN poor stability, drug loading is low, has limited its application.
NLC is a kind of new colloidal drug-supplying system that develops on the SLN basis, be to have added liquid lipid on SLN prescription basis, cause the lipid molecular crystal defect, increased the randomness of crystal, thereby can hold more medicine, also improve Systems balanth simultaneously.Therefore, NLC not only has the advantage of SLN, such as the control drug release, improves the dissolubility of insoluble drug, good biocompatibility and biodegradable etc.The problem of also having avoided the entrapment efficiency of SLN and liposome low, being easy to reveal.Therefore, the present invention is prepared into nano-lipid carrier with Tamibarotene, improves its dissolubility in the hope of reaching, and prolongs in vivo circulation time, improves to absorb, and improves bioavailability, changes the purpose of medicine distribution in vivo.
Summary of the invention
For above-mentioned prior art, the invention provides a kind of Novel Drug Delivery Systems of Tamibarotene intravenous administration---Tamibarotene nano-lipid carrier, this drug-supplying system have the characteristics such as toxicity is little, biodegradable, higher at blood middle concentration, the length of holding time.The present invention also provides the preparation method of Tamibarotene nano-lipid carrier.
The present invention is achieved by the following technical solutions:
A kind of Tamibarotene nano-lipid carrier is composed of the following components:
Described solid lipid material is selected from any one or more combination in glyceryl monostearate, triglyceride, fatty acid, wax or the sterin.Described triglyceride comprises glyceryl tristearate, tripalmitin, trilaurin, myristin; Described fatty acid comprises stearic acid, Palmic acid, capric acid, sad, behenic acid, myristic acid etc.; Described wax comprises cetyl palmitate, spermol cetylate; Described sterin comprises cholesterol, steroidal.Preferably, described solid lipid material is selected from any one or more combination in glyceryl monostearate, stearic acid, cholesterol or the tripalmitin.
Described liquid lipid is selected from any one or more combination in crude vegetal, medium chain length fatty acid triglyceride, oleic acid, linoleic acid, isopropyl myristate, VitAVitE, vitamin ester or the fish oil.Described crude vegetal comprises soybean oil, Oleum Arachidis hypogaeae semen, safflower oil, Oleum Helianthi, olive oil; Described medium chain length fatty acid triglyceride is that chain length is at C
8～C
10Between medium chain length fatty acid triglyceride.Preferably, described liquid lipid is selected from any one or more combination in oleic acid, soybean oil or the vitamin E.
Described fat-soluble emulsifier is selected from phospholipid, the fatty acid Pyrusussuriensis is smooth or Polysorbate in any one or more combinations; Described phospholipid comprises soybean lecithin, Ovum Gallus domesticus Flavus lecithin, lecithin, hydrolecithin; Smooth Span60, the Span80 of comprising of described fatty acid Pyrusussuriensis; Described Polysorbate comprises Tween60, Tween80.Preferably, described fat-soluble emulsifier is selected from any one or more combination among lecithin, soybean lecithin, Ovum Gallus domesticus Flavus lecithin or the Tween80.
Described water soluble emulsifier is selected from any one or more combination in PLURONICS F87 (F68), poloxamer 182, polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether or the sodium lauryl sulphate.Preferably, described water soluble emulsifier is selected from PLURONICS F87 (F68) or poloxamer 182.
Further, in order to adapt to intravenous requirement, preferred emulsifying agent consists of soybean lecithin (fat-soluble emulsifier) and F68(water soluble emulsifier).
The preparation method of described Tamibarotene nano-lipid carrier is melting-emulsifying-low-temperature setting method, is about to medicine, solid lipid material, liquid lipid and fat-soluble emulsifier and is dissolved in organic solvent, the high-temperature heating melting; Water soluble emulsifier is dissolved in water for injection, and is heated to uniform temp; Then oil phase slowly splashes into water, high temperature emulsifying; With the colostrum low-temperature setting that makes, concrete steps are as follows:
(1) precision takes by weighing Tamibarotene, solid lipid material, liquid lipid and fat-soluble surfactant, ultrasonic it is dissolved in the organic solvent, and heating in water bath to 70～80 ℃ form oil phase, and are for subsequent use;
(2) water soluble emulsifier is dissolved in an amount of water for injection, heating in water bath to 70～80 ℃, as water, for subsequent use;
(3) be under the condition of electromagnetic agitation of 500～1000rpm at rotating speed, with micro-injection pump oil phase slowly splashed into water, continue emulsifying 30min～60min, and keep constant temperature to stir, until organic solvent volatilizees fully, form colostrum;
(4) colostrum that step (3) is obtained is inserted 0～2 ℃ ice-water bath, low-temperature setting, the preferred 60min of rotating speed electromagnetic agitation 30～80min(with 500～1000rpm), making outward appearance is light blue translucent colloidal suspension, is the Tamibarotene nano-lipid carrier.
Further, further comprising the steps of:
(5) freeze drying protectant that adds 1～10wt% in the Tamibarotene nano-lipid carrier that makes in the step (4); get Tamibarotene nano-lipid carrier lyophilized formulations; be sub-packed in the 5mL cillin bottle; put-80 ℃ of ultra cold storage freezer pre-freeze 24h; place freezer dryer; lyophilizing 48h measures water content and answers ﹤ 0.01%, takes out to seal to get final product.
In the described step (1), organic solvent is selected from any one or any two or more mixture in dehydrated alcohol, acetone, chloroform, dichloromethane or the oxolane.
In the described step (3), the rate of addition of micro-injection pump is 10～50mL/h.
In the described step (5), described freeze drying protectant is selected from any one or any two or more mixture in mannitol, lactose, glucose, sodium chloride or the trehalose.
The prepared Tamibarotene nano-lipid carrier particle diameter of the present invention is at 100～200nm, and injection for intravenous uses, and compares with peroral dosage form, can reduce dosage, possess in vivo the slow release characteristics, but the time of prolong drug in blood is improved bioavailability.
Tamibarotene nano-lipid carrier drug-supplying system of the present invention has the following advantages:
(1) used carrier material of the present invention is lipid, and toxicity is low, and is biodegradable, and good biocompatibility has improved the body toleration;
(2) this system has overcome the shortcoming that the drug loading of solid lipid nanoparticle is low, medicine easily leaks, and makes the preparation can storage-stable; By freeze drying process described nano-lipid carrier is made freeze-drying prods, further improved the stability of preparation;
(3) technique of the present invention is melting-emulsifying-low-temperature setting method, and preparation process is simple, and maturation is suitable for industrialized great production;
(4) preparation of the present invention can dilute or disperses with normal saline or glucose injection, be used for intravenous administration, little (the equal Li Jing of Ping＜=200nm) of nanoparticle granularity in the preferred technical scheme (embodiment 1), narrow (PI＜=0.3) distributes, envelop rate is high, the effectiveness and the safety that help to improve preparation.
The present invention has following beneficial effect: the Novel Drug Delivery Systems that 1. a kind of Tamibarotene intravenous administration is provided, be the Tamibarotene nano-lipid carrier, this drug-supplying system has the characteristics such as toxicity is little, biodegradable, higher at blood middle concentration, the length of holding time.2. adopt the Tamibarotene nano-lipid carrier of melting-emulsifying preparation can control drug release, change the medicine characteristics of pharmacokinetics; Can also avoid in body circulation that mononuclear cell is huge bites system (MPS), thereby reach passive target and change the medicine purpose that distributes in vivo.3. the Tamibarotene nano-lipid carrier of the present invention's preparation can overcome leakage and the low shortcoming of envelop rate of solid lipid nanoparticle and lipidosome Chinese traditional medicine thing, thereby improve Systems balanth.4. the Tamibarotene nano-lipid carrier of the present invention preparation, Tamibarotene nano-lipid carrier intravenous administration can reduce dosage, reduces administration number of times, reaches the therapeutic effect identical with the listing preparation, thereby is expected to improve patient's compliance.
Description of drawings
Fig. 1 is: Tamibarotene nano-lipid carrier transmission electron microscope photo.
Fig. 2: Tamibarotene nano-lipid carrier particle size distribution figure.
Fig. 3: Tamibarotene nano-lipid carrier release in vitro gets total release percentage-time plot, wherein, and A: Tamibarotene nano-lipid carrier lyophilized formulations; B: Tamibarotene nano-lipid carrier.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment.
Embodiment 1 preparation Tamibarotene nano-lipid carrier
Precision takes by weighing Tamibarotene 10mg, stearic acid 20mg, glyceryl monostearate 30mg, soybean lecithin 50mg, oleic acid 20mg, is dissolved in the 5mL dehydrated alcohol, puts 75 ℃ of heating in water bath to melting, consists of organic facies; Take by weighing in addition PLURONICS F87 200mg and be dissolved in the 20mL water for injection, be heated to uniform temp, consist of water.Organic facies under stirring, 600r/min is slowly injected water with micro-injection pump with the speed of 15mL/h, (75 ± 2) ℃ constant temperature stirs, organic solvent is fully volatilized, with stirring 1h with 600r/min in the gained colostrum ice-water bath, make the Tamibarotene nano-lipid carrier behind the 1h.
Prepared nanoparticle outward appearance as shown in Figure 1, as seen from the figure Tamibarotene nano-lipid carrier size evenly, the outward appearance rounding.Mean diameter is 189nm, particle size distribution as shown in Figure 2, ζ-potential is-34mv, average envelop rate is 91%, drug loading is 9.05%.
Add the mannitol of 3wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, place-80 ℃ of cryogenic refrigerator pre-freeze 24h, place freezer dryer, lyophilizing 48h takes out to seal and gets final product.
The release in vitro of Tamibarotene nano-lipid carrier lyophilized formulations is achieved in the following ways: take by weighing an amount of Tamibarotene nano-lipid carrier lyophilized formulations, adopt positive Dynamic Membrane dialysis, with the pH7.4PBS that contains 3wt%Tween80 as release medium, rotating speed 100rpm, temperature is (37.5 ± 0.5) ℃.With the bag filter (molecular cut off 8000～14000) of the suspension of the above-mentioned lyophilized formulations of 2mL is housed, place release medium.Draw release medium 0.5mL respectively at 0.17,0.5,1,2,4,6,8,12,24,36,48h, fill into simultaneously the release medium of equality of temperature, sample introduction 20 μ L carry out high-efficient liquid phase analysis behind the sample filtering.Calculate the cumulative release percentage rate, shown in Fig. 3-A, as seen from the figure, the release in vitro of Tamibarotene nano-lipid carrier is two-phase, and namely front 8h discharges comparatively fast, and then release ratio is slower.
The release in vitro of Tamibarotene nano-lipid carrier is achieved in the following ways: adopt equally the Dynamic Membrane dialysis, accurate absorption Tamibarotene nano-lipid carrier 2mL places the bag filter of molecular cut off 8000～14000, bag filter is placed release medium, the condition that other conditions discharge with lyophilized formulations.Draw release medium 0.5mL respectively at 0.17,0.5,1,2,4,6,8,12,24,36,48h, fill into simultaneously the release medium of equality of temperature, sample introduction 20 μ L carry out high-efficient liquid phase analysis behind the sample filtering.Calculate the cumulative release percentage rate, shown in Fig. 3-B.
Embodiment 2 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 10mg, glyceryl monostearate 40mg, oleic acid 30mg, soybean lecithin 50mg, uses the 5mL acetone solution, and 75 ℃ of heating in water bath form oil phase.Other gets PLURONICS F87 200mg and is dissolved in the 20mL water for injection, and heating in water bath consists of water as for the identical temperature of organic facies.Organic facies is slowly injected water with micro-injection pump with the speed of 20mL/h under 600rpm stirs, (75 ± 2) ℃ constant temperature stirs, and waves most organic solvent, stirs 30min with 600rpm again under 0～2 ℃ of ice-water bath, makes the Tamibarotene nano-lipid carrier.
Add the lactose of 3wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, place-80 ℃ of cryogenic refrigerator pre-freeze 24h, place freezer dryer, lyophilizing 48h takes out to seal and gets final product.
Embodiment 3 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 15mg, stearic acid 20mg, glyceryl monostearate 30mg, soybean oil 20mg, lecithin 40mg, is dissolved in the 5mL chloroform, and 75 ℃ of heating in water bath form oil phase.Other measures 20mL water for injection, and heating in water bath is to the temperature identical with organic facies, as water.Organic facies is splashed into water with micro-injection pump with the speed of 15mL/h, and stir 1h with the speed of 600rpm, with the volatilization organic solvent.The gained colostrum is stirred 40min with 600rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
Add the glucose of 3wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, place-80 ℃ of cryogenic refrigerator pre-freeze 24h, place freezer dryer, lyophilizing 48h takes out to seal and gets final product.
Embodiment 4 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 5mg, glyceryl monostearate 30mg, cholesterol 20mg, oleic acid 20mg, lecithin 40mg, is dissolved in the 5mL dehydrated alcohol, and 75 ℃ of heating in water bath form oil phase.Other measures 20mL water for injection, adds poloxamer 182200mg, and heating in water bath is to the temperature identical with organic facies, as water.Speed with 15mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 600rpm, waves most organic solvent.The gained colostrum is continued to stir 50min with 600rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
The mannitol that adds 6wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Embodiment 5 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 10mg, tripalmitin 30mg, cholesterol 20mg, soybean oil 20mg, soybean lecithin 50mg, is dissolved in the 5mL chloroform, and 75 ℃ of heating in water bath form oil phase.Other gets PLURONICS F87 200mg and is dissolved in the 20mL water for injection, and heating in water bath consists of water as for the identical temperature of organic facies.Speed with 15mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 600rpm, waves most organic solvent.The gained colostrum is continued to stir 1h with 600rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
The lactose that adds 6wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Embodiment 6 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 20mg, stearic acid 20mg, glyceryl monostearate 30mg, soybean oil 20mg, soybean lecithin 40mg, is dissolved in the 5mL dehydrated alcohol, puts 75 ℃ of heating in water bath to melting, consists of organic facies.Other gets PLURONICS F87 200mg and is dissolved in the 20mL water for injection, and heating in water bath consists of water as for the identical temperature of organic facies.Speed with 25mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 800rpm, waves most organic solvent.The gained colostrum is continued to stir 70min with 800rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
The glucose that adds 6wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Embodiment 7 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 10mg, tripalmitin 30mg, glyceryl monostearate 30mg, soybean oil 20mg, soybean lecithin 40mg, is dissolved in the 5mL dehydrated alcohol, puts 75 ℃ of heating in water bath to melting, consists of organic facies.Take by weighing in addition PLURONICS F87 200mg and be dissolved in the 20mL water for injection, be heated to uniform temp, consist of water.Speed with 25mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 600rpm, waves most organic solvent.The gained colostrum is continued to stir 80min with 600rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
The mannitol that adds 9wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Embodiment 8 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 5mg, tripalmitin 30mg, stearic acid 20mg, vitamin E2 0mg, Tween80100mg, is dissolved in the 5mL dehydrated alcohol, puts 75 ℃ of heating in water bath to melting, consists of organic facies.Other takes by weighing sodium lauryl sulphate 200mg and is dissolved in the 20mL water for injection, is heated to uniform temp, consists of water.Organic facies is slowly injected water with micro-injection pump with the speed of 15mL/h under 800rpm stirs, (75 ± 2) ℃ constant temperature stirs, and waves most organic solvent, stirs 1h with 800rpm again under 0～2 ℃ of ice-water bath, makes the Tamibarotene nano-lipid carrier.
The lactose that adds 9wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Embodiment 9 preparation Tamibarotene nano-lipid carriers
Precision takes by weighing Tamibarotene 10mg, stearic acid 20mg, glyceryl monostearate 30mg, vitamin E2 0mg, Tween80100mg, is dissolved in the 5mL acetone, puts 75 ℃ of heating in water bath to melting, consists of organic facies.Other gets PLURONICS F87 200mg and is dissolved in the 20mL water for injection, and heating in water bath consists of water as for the identical temperature of organic facies.Speed with 15mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 600rpm, waves most organic solvent.Speed with 10mL/h splashes into water with micro-injection pump, and stirs 1h with the speed of 600rpm, waves most organic solvent.The gained colostrum is continued to stir 40min with 600rpm under 0～2 ℃ of ice-water bath, make the Tamibarotene nano-lipid carrier.
The glucose that adds 9wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Precision takes by weighing Tamibarotene 15mg, glyceryl tristearate 20mg, trilaurin 30mg, lecithin 40mg, is dissolved in the 5mL chloroform, and 75 ℃ of heating in water bath form oil phase.Other gets PLURONICS F87 200mg and is dissolved in the 20mL water for injection, and heating in water bath consists of water as for the identical temperature of organic facies.Organic facies is slowly injected water with micro-injection pump with the speed of 25mL/h under 600rpm stirs, (75 ± 2) ℃ constant temperature stirs, and waves most organic solvent, stirs 80min with 600rpm again under 0～2 ℃ of ice-water bath, makes the Tamibarotene nano-lipid carrier.
The mannitol that adds 10wt% in the Tamibarotene nano-lipid carrier that makes, then in packing and the 5mL cillin bottle, first-20 ℃ of pre-freezes, ℃ pre-freeze 24h places freezer dryer again-80, and lyophilizing 48h takes out to seal and gets final product.
Claims (10)
1. Tamibarotene nano-lipid carrier is characterized in that: be composed of the following components:
2. Tamibarotene nano-lipid carrier according to claim 1, it is characterized in that: described solid lipid material is selected from any one or more combination in glyceryl monostearate, triglyceride, fatty acid, wax or the sterin.
3. Tamibarotene nano-lipid carrier according to claim 1, it is characterized in that: described liquid lipid is selected from any one or more combination in crude vegetal, medium chain length fatty acid triglyceride, oleic acid, linoleic acid, isopropyl myristate, VitAVitE, vitamin ester or the fish oil.
4. Tamibarotene nano-lipid carrier according to claim 1 is characterized in that: described fat-soluble emulsifier is selected from phospholipid, the fatty acid Pyrusussuriensis is smooth or Polysorbate in any one or more combinations.
5. Tamibarotene nano-lipid carrier according to claim 1, it is characterized in that: described water soluble emulsifier is selected from any one or more combination in PLURONICS F87, poloxamer 182, polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether or the sodium lauryl sulphate.
6. the preparation method of each described Tamibarotene nano-lipid carrier in the claim 1～5 is characterized in that: may further comprise the steps:
(1) precision takes by weighing Tamibarotene, solid lipid material, liquid lipid and fat-soluble surfactant, ultrasonic it is dissolved in the organic solvent, and heating in water bath to 70～80 ℃ form oil phase, and are for subsequent use;
(2) water soluble emulsifier is dissolved in the water for injection, heating in water bath to 70～80 ℃, as water, for subsequent use;
(3) be under the condition of electromagnetic agitation of 500～1000rpm at rotating speed, with micro-injection pump oil phase slowly splashed into water, continue emulsifying 30min～60min, and keep constant temperature to stir, until organic solvent volatilizees fully, form colostrum;
(4) colostrum that step (3) is obtained is inserted 0～2 ℃ ice-water bath, low-temperature setting, and with rotating speed electromagnetic agitation 30～80min of 500～1000rpm, making outward appearance is light blue translucent colloidal suspension, is the Tamibarotene nano-lipid carrier.
7. preparation method according to claim 6; it is characterized in that: further comprising the steps of: add the freeze drying protectant of 1～10wt% in the Tamibarotene nano-lipid carrier that (5) make in the step (4), get Tamibarotene nano-lipid carrier lyophilized formulations.
8. according to claim 6 or 7 described preparation methoies, it is characterized in that: in the described step (1), organic solvent is selected from any one or any two or more mixture in dehydrated alcohol, acetone, chloroform, dichloromethane or the oxolane.
9. according to claim 6 or 7 described preparation methoies, it is characterized in that: in the described step (3), the rate of addition of micro-injection pump is 10～50mL/h.
10. according to claim 6 or 7 described preparation methoies, it is characterized in that: in the described step (5), described freeze drying protectant is selected from any one or any two or more mixture in mannitol, lactose, glucose, sodium chloride or the trehalose.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013600A (en) * | 2014-06-05 | 2014-09-03 | 暨南大学 | Psoralen-enveloped nanostructure lipid carrier preparation and preparation method thereof |
| CN112266551A (en) * | 2020-10-27 | 2021-01-26 | 青岛创宇塑胶制品有限公司 | Antibacterial and antistatic edge band and preparation method thereof |
| US11039995B2 (en) | 2013-03-15 | 2021-06-22 | Samson Pharma, Llc | Topical compositions for reducing the effects of aging |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1883455A (en) * | 2006-07-07 | 2006-12-27 | 中国科学院上海药物研究所 | A long-circulating nanoliposome carrier of hydroxycamptothecine and preparation method thereof |
| CN101632638A (en) * | 2009-08-21 | 2010-01-27 | 山东大学 | Silybin nanostructured lipid carrier and preparation method thereof |
-
2012
- 2012-12-19 CN CN2012105554283A patent/CN102961346A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1883455A (en) * | 2006-07-07 | 2006-12-27 | 中国科学院上海药物研究所 | A long-circulating nanoliposome carrier of hydroxycamptothecine and preparation method thereof |
| CN101632638A (en) * | 2009-08-21 | 2010-01-27 | 山东大学 | Silybin nanostructured lipid carrier and preparation method thereof |
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