CN1771967A - Oryzanol liposome and its prepn - Google Patents
Oryzanol liposome and its prepn Download PDFInfo
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- CN1771967A CN1771967A CN 200410094556 CN200410094556A CN1771967A CN 1771967 A CN1771967 A CN 1771967A CN 200410094556 CN200410094556 CN 200410094556 CN 200410094556 A CN200410094556 A CN 200410094556A CN 1771967 A CN1771967 A CN 1771967A
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Abstract
The present invention is oryzanol liposome with high absorption, high bioavailability and high stability and its preparation. The oryzanol liposome or oryzanol liposome precursor is prepared with oryzanol and phosphatide, cholesterol, supporting agent and other supplementary material. It has phosphatide/medicine weight ratio of 0.1-40, and is prepared through ethanol injecting process, film dispersion process, inverse evaporation process, extruding process or mechanical process. The supporting agent may be sorbitol, mannitol, cane sugar, etc. and has ratio to phosphatide of 0.01-400. The oryzanol liposome can act selectively on the autonomic nerve system of interbran and the center of endocrine system to improve autonomic nerve system, endocrine system and psychonerve. It is suitable for treating neurosis, climacteric syndrome, etc., and may be used in the assisting treatment of vascular headache and cerebral concussion sequelae.
Description
Technical field
The present invention relates to medical technical field, exactly it is a kind of oryzanol liposome (comprising pro-liposome) and preparation method thereof.
Background technology
Oryzanol (oryzanol) another name: ferulic acid ester; R-orizanol; Gammatsul; Thiaminogen.Separating from Testa oryzae oil, is the mixture based on the ferulic acid ester of triterpene alcohol.The autonomic nerve system that optionally the acts on diencephalon maincenter of hormonal system of unifying can improve autonomic nervous dysfunction, improves incretion balance obstacle and spiritual nervous disorder.Be used for various neurosiss, climacteric syndrome, pre-menstrual period nercousness, periodic psychosis etc.The auxiliary treatment that also can be used for vascular headache and cerebral concussion sequela.The antiinflammatory action foreign medical science of gamma oryzanol. it is lubricant component in the Testa oryzae that 2004 03 phase He Yu of Chinese medicine fascicle chisel oryzanol, and its main component is cyclic-ahltin base ferulic acid ester, 24-methylene cyclic-ahltin base ferulic acid ester etc.The g-oryzanol has pharmacological actions such as antioxidation, antibiotic, antitumor.In recent years studies show that the ferulic acid ester in Rhizoma Et Radix Notopterygii, the Rhizoma Atractylodis has the activity that suppresses LPO and COX.This in research g-oryzanol ferulic acid ester to LPO or COX effect in, inquired into its effect to adjuvant arthritis.1. be subjected to the preparation of test product: cyclic-ahltin base ferulic acid ester (1), 24-methylene cyclic-ahltin base ferulic acid ester (2) separate from the g-oryzanol and obtain.2. LPO suppresses activity test: get 200mM borate buffer (pH 9.0) 1960mL, add 1000U/mL LPO 20mL and be subjected to test product 20mL, room temperature reaction 5min adds substrate linolenic acid 50mL, puts 37 ℃ of reactions.This heavily fortified point of 2004 03 phase kings of novel clinical use China clinician of oryzanol, Wang Baolin, Jiang Xindao oryzanol (Oryzanol has another name called and holds Rui Saluo, ferulic acid ester) is present in the Testa oryzae oil, is the mixture based on the A Wei acid esters of triterpene alcohol.This medicine acts on the autonomic nervous system and the secretion maincenter of diencephalon, can adjust autonomic nervous function, reduces the incretion balance obstacle, improves spiritual nervous disorder symptom.Be mainly used in gynecological's climacteric syndrome, premenstrual tension syndrome, neuralgia etc.2004 05 phase Lang Li of the practical sacred disease magazine of the migrainous observation of curative effect of flunarizine, diclofenac sodium, oryzanol therapeutic alliance and, Duan Yanjun, Zhang Jianbo 1998 so far, we use flunarizine, diclofenac sodium, oryzanol therapeutic alliance migraineur 130 examples, obtain remarkable result, now the result is reported as follows.1 data and method 1.1 cases are selected the migraine diagnostic criteria of formulating according to international headache association in 1998, select the common or typicality of the course of disease 〉=June, every month seizure frequency 〉=1 time.Oryzanol and vitamin B _ 1 strengthens 2003 04 phase Zhang Hui of clinical verification China's clinical pharmacy magazine of diazepam angst resistance effect, Yang Guangsheng checking oryzanol and vitamin B _ 1 strengthen the angst resistance effect of diazepam, inquire into and reduce the diazepam consumption, reduce the new way of adverse effect.Method: 60 routine anxiety patients are divided into 2 groups at random: matched group 30 examples, list is treated with diazepam; 30 examples are organized in treatment, after list is used the diazepam controlling symptoms earlier, singly reduce by half by the each patient again with the diazepam effective dose, and with oryzanol 20mg, vitamin B _ 1 20mg combination therapy.Be 4wk the course of treatment.Observe the curative effect and untoward reaction situation.The result: effective controlling symptoms person's 26 examples are organized in treatment, account for 86.7%, and effective controlling symptoms person's 27 examples of matched group account for 90.0% (P＞0.05); But treatment group adverse reaction rate is starkly lower than matched group.Conclusion: will tie up element and vitamin B _ 1 and can strengthen the diazepam angst resistance effect, and reduce the untoward reaction of diazepam.2003 29 phase Guo Mingxing of clinical new usage Shandong of oryzanol medicine oryzanol in recent years remove clinical being used for the treatment of the neural decline, treating aspect other disease also more and more widely, now are reported as follows.Be used for hyperlipemia: oryzanol has tangible effect for reducing blood fat, especially the curative effect to triglyceride reducing is more remarkable, the therapeutic equivalence that reduces mannitol is in inositol niacinate, and it is harmless to liver, having overcome most of blood lipid-lowering medicines newly uses the old medicine of the shortcoming of liver injury---and oryzanol Family Medical 08 phase of the calendar year 2001 dragon oryzanol of pacifying the people has another name called Hi-Z, is mainly used in autonomic nervous dysfunction disease, climacteric syndrome, cerebral concussion sequela, premenstrual tension etc. clinically.In recent years,, find a lot of new purposes of oryzanol, now be described below along with clinical pharmacological research and repeatedly practising.Treatment peptic ulcer oryzanol can suppress the pepsine secretion, reduces or the control gastric acid secretion, plays the effect of treatment gastric ulcer.30 milligrams of oral every days, 2 months is a course of treatment.Treatment dysfunctional uterine hemorrhage oryzanol acts on diencephalon hypothalamus and antepituitary, has the effect of regulating vegetative nerve function and endocrine regulation, thereby the treatment primary disease has good effect.Oryzanol: tablet, productions such as Beijing, Beijing pharmaceutical factory.Every contains 10 milligrams of oryzanol, 100 every bottle.Oryzanol polylactic acid nanoparticle lyophilized injection; Bioavailability is low, and oryzanol is made liposome and pro-liposome is not seen recommendation.
Summary of the invention
The purpose of this invention is to provide oryzanol liposome and pro-liposome and preparation method thereof, poor to improve the oryzanol oral absorption, and bioavailability is low.As the phospholipid of film material, itself is nontoxic, and can strengthen body immunity, has many health cares simultaneously.
The present invention adds cholesterol by oryzanol and phospholipid, also can not add (nanometer) liposome that adjuvants such as cholesterol are prepared from.Preparation method can adopt pro-liposome method, alcohol injection, film dispersion method, reverse phase evaporation, PH gradient method, extrusion molding, Mechanical Method etc. to prepare the whole bag of tricks of liposome and nanometer liposome.Mechanical Method can be the method that various plant equipment such as dispersing emulsification machine, high pressure dispersing emulsification machine, nanometer machine, refiner, high pressure microjet prepare liposome.The phospholipid of preparation liposome, can be soybean lecithin, hydrogenated soya phosphatide, it also can be synthetic phospholipid, prepare oryzanol liposome by alcohol injection, film dispersion method, reverse phase evaporation, extrusion molding, Mechanical Method, its composition comprises: adjuvants such as oryzanol phospholipid, cholesterol, VE. wherein the weight ratio of phospholipid and oryzanol is 0.1: 1～40: 1, and the weight ratio of C/PL is 0～2: 1.
The prescription that is equipped with liposome by the pro-liposome legal system is: oryzanol, proppant, phospholipid, cholesterol, VE etc.The weight ratio of phospholipid and oryzanol is 0.1: 1～40: 1, and the weight ratio of C/PL is 0～2: 1, and the ratio of proppant and phospholipid is 0.01: 1～400: 1.Proppant can be used medicinal materials or the pharmaceutic adjuvants that can be used for frozen-dried supporting agent such as sorbitol, mannitol, sucrose, sodium chloride, water soluble starch, dextran, glucose, lactose.The method for preparing proliposome can adopt various prilling process and drying and coating methods such as decompression rotating thin film method, spray drying method, fluidized bed process or lyophilization.Adding water or buffer before pro-liposome uses forms liposome, or is prepared into capsule, tablet, granule etc. by jolting, stirring, ultrasonic aquation.In digestive tract, meet the direct spontaneous formation liposome of water.
Can make dosage forms such as tablet, oral liquid, oral breast, capsule, granule, injection, freeze-dried powder, transfusion Emulsion, microemulsion, injectable powder with oryzanol liposome (or precursor fat body).
Advantage of the present invention is: it is poor to improve the oryzanol oral absorption, and the deficiency that bioavailability is low utilizes phospholipid to make the film material, and oryzanol is made liposome, and phospholipid can be worked in coordination with and assosting effect with the oryzanol performance, improves the curative effect of oryzanol.
The specific embodiment:
Concrete preparation method of the present invention is illustrated by following embodiment, but protection scope of the present invention is not limited to this.
Embodiment 1:
Alcohol injection prepares oryzanol liposome: get soybean phospholipid, cholesterol, VE inject the oryzanol aqueous solution after adding anhydrous alcohol solution, the constant temperature high-speed stirred, reduction vaporization is removed ethanol, crosses the microporous filter membrane granulate, promptly get oryzanol liposome, envelop rate can reach 60.8%.
Embodiment 2:
Film dispersion method prepares oryzanol liposome: get soybean phospholipid, cholesterol, VE is dissolved in the 150ml eggplant-shape bottle with the 15ml chloroform, the film forming that reduces pressure on rotary film evaporator also eliminates organic solvent, add 10ml oryzanol aqueous solution aquation, cross the microporous filter membrane granulate, get oryzanol liposome, envelop rate can reach 59.1%.
Embodiment 3:
Reverse phase evaporation prepares oryzanol liposome: take by weighing soybean phospholipid, cholesterol, VE adds the 5ml chloroform makes dissolving, add the 10ml ether again, add then in the phosphate buffer of 15ml oryzanol, ultrasonic the making of bath formula forms the homogeneous single_phase system, evaporation under reduced pressure removed chloroform ether is to gel formation, continued reduction vaporization 5～10 minutes, it is that liposome forms that vortex vibrates to aqueous suspension.Envelop rate can reach 25.5%.
Embodiment 4:
Decompression rotating thin film legal system is equipped with the oryzanol pro-liposome: get sorbitol and oryzanol and be placed in the 100ml eggplant-shape bottle with the equivalent method mix homogeneously that progressively increases, in decompression preheating on the Rotary Evaporators of improvement 30 minutes, get soybean phospholipid, cholesterol, VE and be dissolved in ethanol liquid, rotary evaporation in vacuo in right amount.All add the back at ethanol liquid and continued reduction vaporization 30～40 minutes, powder is taken out sieve (40 orders, 450 μ m) after placing exsiccator to spend the night, promptly get the oryzanol pro-liposome.Envelop rate can reach 22.8%.
Embodiment 5:
Fluidized bed process prepares the oryzanol pro-liposome: sorbitol and oryzanol are placed in the fluid bed with the equivalent method mix homogeneously that progressively increases, getting soybean phospholipid, cholesterol, VE is dissolved in the dehydrated alcohol in right amount, by fluid bed boiling one-step palletizing, sieve, promptly get the oryzanol pro-liposome.
Embodiment 6:
Fluidized bed process prepares the oryzanol pro-liposome: the oryzanol adding distil water, and add 0.1N NaOH again and transfer PH to make dissolving, adjust volume (A liquid) with distilled water; Other gets soybean phospholipid, cholesterol, VE and is dissolved in the dehydrated alcohol, by fluid bed boiling one-step palletizing, crosses 20 orders and 60 mesh sieves, promptly gets oryzanol pro-liposome granule.
Embodiment 7:
Spray drying method for preparation oryzanol pro-liposome: oryzanol adds water, and 0.1N NaOH transfers PH to make dissolving, adds lactose and EDTA and makes dissolving (A liquid).Other gets soybean phospholipid, cholesterol, VE and is dissolved in (B liquid) in the 100ml dehydrated alcohol.B liquid is under agitation slowly added in the A liquid, and spray-drying process sieves, and promptly gets oryzanol liposome.
Embodiment 8:
The liposome of alcohol injection, film dispersion method preparation, spray drying promptly gets the oryzanol pro-liposome.
Embodiment 9:
Prepare oryzanol liposome by pro-liposome.Get the pro-liposome 2g that embodiment 7 makes,, add water 10ml jolting 10 minutes and aquation, promptly get oryzanol liposome, microscope amplifies 1000 times of observations can see liposome.
Embodiment 10:
Freeze-drying prepares the oryzanol pro-liposome: soybean phospholipid, cholesterol, an amount of VE slowly inject the oryzanol aqueous solution in high-speed stirred after adding anhydrous alcohol solution, and reduction vaporization is removed ethanol.Lyophilization 24 hours gets the oryzanol pro-liposome.
Embodiment 11:
Oryzanol liposome is crossed the sterilization of 0.22 μ m microporous filter membrane, inflated with nitrogen, embedding gets the oryzanol liposome injection.
Embodiment 12:
Oryzanol liposome is added 10% sucrose, cross the sterilization of 0.22 μ m microporous filter membrane, packing, lyophilization gets injectable powder.
Embodiment 13:
The oryzanol pro-liposome is sieved, and packing gets the oryzanol liposome granule.
Embodiment 14:
The oryzanol pro-liposome is sieved, encapsulated, get the oryzanol liposome capsule.
Embodiment 15:
The oryzanol pro-liposome is sieved, and tabletting gets the oryzanol liposome tablet.
The invention is not restricted to above-described embodiment.
Claims (8)
1, oryzanol liposome and preparation method thereof is characterized in that: the liposome or the pro-liposome that are prepared from by adjuvants such as oryzanol and phospholipid.
2, oryzanol liposome according to claim 1 is characterized in that: wherein can add cholesterol and proppant.
3, oryzanol liposome according to claim 1 or pro-liposome is characterized in that: film material phospholipid can adopt natural phospholipid, also can be to adopt hydrogenated soya phosphatide and synthetic phospholipid etc.
4, oryzanol liposome according to claim 1 or pro-liposome is characterized in that: the weight ratio of phospholipid and medicine is 0.1: 1～40: 1. and oryzanol 5--100mg.
5, oryzanol liposome or the pro-liposome of stating according to claim 2, it is characterized in that: proppant can sorbitol, mannitol, sucrose, sodium chloride, water soluble starch, dextran, stevioside, glucose, lactose etc., and wherein the ratio of proppant and phospholipid is: 0.01: 1～400: 1.
6, oryzanol liposome according to claim 1 or pro-liposome is characterized in that: can make dosage forms such as capsule, tablet, granule, injection, oral liquid, freeze-dried powder, transfusion with this liposome or pro-liposome.
7, a kind of preparation method of oryzanol liposome as claimed in claim 1 is characterized in that: preparation method can adopt pro-liposome method, alcohol injection, film dispersion method, reverse phase evaporation, extrude instrument, Mechanical Method, PH gradient method etc.; Mechanical Method comprises that various plant equipment such as using homogenizer, dispersing emulsification machine, extruder, nanometer machine, refiner, high pressure microjet prepare the method for liposome.
8, a kind of preparation method of oryzanol pro-liposome as claimed in claim 7, it is characterized in that: adopt the pro-liposome legal system to be equipped with oryzanol liposome, prepare pro-liposome earlier, pro-liposome by preparation forms liposome before use, or pro-liposome is prepared into capsule, tablet, granule etc., the direct spontaneous formation liposome of chance water in digestive tract.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410094556 CN1771967A (en) | 2004-11-09 | 2004-11-09 | Oryzanol liposome and its prepn |
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| CN 200410094556 CN1771967A (en) | 2004-11-09 | 2004-11-09 | Oryzanol liposome and its prepn |
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| CN1771967A true CN1771967A (en) | 2006-05-17 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103041392A (en) * | 2012-12-31 | 2013-04-17 | 北京科源创欣科技有限公司 | Composition of oryzanol and proton pump inhibitor |
| CN112843006A (en) * | 2021-01-28 | 2021-05-28 | 上海嘉申医药研发有限公司 | Oryzanol phospholipid complex and preparation method and application thereof |
-
2004
- 2004-11-09 CN CN 200410094556 patent/CN1771967A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103041392A (en) * | 2012-12-31 | 2013-04-17 | 北京科源创欣科技有限公司 | Composition of oryzanol and proton pump inhibitor |
| CN112843006A (en) * | 2021-01-28 | 2021-05-28 | 上海嘉申医药研发有限公司 | Oryzanol phospholipid complex and preparation method and application thereof |
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