CN1634033A - Triptolide nano lipsome gelling agent of external use and its preparation method - Google Patents
Triptolide nano lipsome gelling agent of external use and its preparation method Download PDFInfo
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- CN1634033A CN1634033A CN 200410052121 CN200410052121A CN1634033A CN 1634033 A CN1634033 A CN 1634033A CN 200410052121 CN200410052121 CN 200410052121 CN 200410052121 A CN200410052121 A CN 200410052121A CN 1634033 A CN1634033 A CN 1634033A
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Abstract
The invention relates to a triptolide nano lipsome gelling agent of external use and its preparation method, which comprises externally used gelling agent composed of 10-70% of triptolide alcohol nano liposome turbid liquor and 90-30% of blank gel, wherein the weight ratio content of the triptolide alcohol in the total gelling agent is 0.1-2.0%, and the triptolide alcohol alcohol nano liposome turbid liquor comprises 0.7-4.2% of triptolide alcohol, 14-64% of phosphatides, 3.5-16% of cholesterin, 0.7-3.2% of anti-oxidant, 0.7-3.2% of surface active agent, and hydration medium. Its preparing process is also disclosed in the invention.
Description
Technical field:
The present invention relates to a kind of pharmaceutical preparation and preparation method thereof, relate in particular to a kind of novel form of Radix Tripterygii Wilfordii lactone alcohol, promptly a kind of Radix Tripterygii Wilfordii lactone alcohol exterior-applied gel that utilizes the preparation of nano-lipid body technique.
Background technology:
Radix Tripterygii Wilfordii is the choice drug of treatment rheumatoid arthritis.Radix Tripterygii Wilfordii lactone alcohol (triptolide) claims Triptolide, triptolide again, is one of main effective ingredient in the Radix Tripterygii Wilfordii, existing existing procucts listing.Pharmacological research shows that Radix Tripterygii Wilfordii lactone alcohol not only can suppress the propagation activation of T, bone-marrow-derived lymphocyte, can also make activated T cell generation apoptosis, stops its further propagation; CAMP level in the rising immunocyte reduces the generation of IL-2 and immunoglobulin.Radix Tripterygii Wilfordii lactone alcohol can also suppress the inflammatory hydrarthrosis that carrageenin, Oleum Tiglii and Freund Freund's complete adjuvant cause, reduce the acute pleurisy infiltration capacity, suppress leukoplania and cotton balls granulation hyperplasia, reduce blood plasma PGE2 content, and adrenal gland's weight and adrenal gland VitC content are not had influence.But its toxicity is also very strong simultaneously, and the occurrence frequency of clinical adverse is far above other medicines.Its untoward reaction mainly occurs in digestive system, urinary system, reproductive system, cardiovascular system, bone marrow and blood system, can cause edema, blood sugar increasing in addition, diplopia etc., thus limited clinical practice.Chinese medicine Radix Tripterygii Wilfordii product clinically has Radix Tripterygii Wilfordii tablet, Glucosidorum Tripterygll Totorum and Radix Tripterygii Wilfordii double-layer tablet at present.These all are oral medications, by gastrointestinal administration, have the bigger problem of toxicity.Drug effect being remained unchanged, even increase, and reduce toxicity significantly, is the problem that this field receives much attention.
The patent disclosure of CN1398612A a kind of nanometer Chinese medicine Radix Tripterygii Wilfordii dosage form and preparation method thereof.Its content mainly is to adopt the solid lipid nano technology to carry out the development of Radix Tripterygii Wilfordii solid lipid nanoparticle.The solid lipid nano technology be a kind of be the nanoparticle that material is made with endogenous physiologically substance-chain saturated fatty acids (stearic acid), its product is the lyophilized powder behind liniment and the removal moisture, if lyophilized powder be for external application is coated skin and also must be faced with preceding and prepared, and liniment is owing to be colloid solution, carry and transport equal inconvenience, and poor stability.
Shortcomings such as conventional external preparation majority is an oil-soluble substrate, has greasy, is difficult for being coated with exhibition, eccysis, and bioavailability is low, stability is not so good, untoward reaction is more are used and have been subjected to certain limitation.
Summary of the invention:
The objective of the invention is to prepare Radix Tripterygii Wilfordii lactone alcohol nanometer liposome exterior-applied gel,, improve the local skin drug level, reduce toxic and side effects, the therapeutic effect of performance Radix Tripterygii Wilfordii lactone alcohol by percutaneous drug delivery.
The technical scheme that is adopted is to achieve the object of the present invention: at first Radix Tripterygii Wilfordii lactone alcohol is made nanometer liposome, then the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome is made exterior-applied gel.
Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation of the present invention is the gel of being made by the compositions of following weight percentage ratio: Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 10～70% and blank gel 90～30%; The weight percent content of Radix Tripterygii Wilfordii lactone alcohol is 0.1～2.0% in total gel.
Described Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor is can adopt by following weight percentages to make: all the other are hydration medium for Radix Tripterygii Wilfordii lactone alcohol 0.7～4.2%, phosphatidase 11 4～64%, cholesterol 3.5～16%, antioxidant 0.7～3.2%, surfactant 0.7～3.2%.
Described blank gel can adopt following weight percentages to make: 1～4% acrylic polymer, 1.4～5.6% weak organic bases, all the other are water.
The phospholipid that the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor is adopted can be with soybean lecithin or Ovum Gallus domesticus Flavus lecithin, preferably soya lecithin; The antioxidant that is adopted can be with vitamins such as vitamin C, E or parabens such as methyl hydroxybenzoate, ethyl ester, propyl ester etc., preferred vitamin E; Described surfactant can adopt sodium cholate or sodium deoxycholate etc., preferred sodium deoxycholate; The hydration medium that is adopted is the phosphate buffer of phosphate buffer such as pH7.4, phosphate buffer or the water of pH6.5, preferably adopts water.
The used preferred carbomer series of acrylic polymer in the blank gel, the preferred triethanolamine of weak organic base.
Another technical problem to be solved by this invention is how to prepare above-mentioned Radix Tripterygii Wilfordii lactone alcohol nanometer liposome exterior-applied gel.
The preparation method of liposome has multiple, as membrane process, reverse phase evaporation, multi-emulsion method, fusion method, injection method etc., the present invention through trial test find with thin film-ultrasonic method and ethanol splash into-the ultrasonic method effect is better.The present invention obtains the basic consumption of each component by the factors such as consumption of phospholipid, cholesterol, antioxidant, surfactant are carried out orthogonal test.
The preparation method of Radix Tripterygii Wilfordii lactone alcohol nanometer plastid exterior-applied gel provided by the present invention is to carry out as follows: one, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor: take by weighing Radix Tripterygii Wilfordii lactone alcohol, phospholipid, cholesterol, antioxidant, surfactant by recipe quantity sodium, be dissolved in the dehydrated alcohol, with thin film-ultrasonic technology or ethanol splash into-ultrasonic technology adds the hydration medium of recipe quantity, the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor; Two, the preparation of blank gel: with recipe quantity acrylic polymer water swelling, organic base is transparent to gel a little less than dripping, the white gel of promptly having leisure; Three, the preparation of gel: by recipe quantity the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor that makes is added in the blank gel, equidirectional stirring and evenly mixing promptly gets Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
Prepare Radix Tripterygii Wilfordii lactone alcohol thin film that nanometer liposome turbid liquor adopts-ultrasonic technology or ethanol specifically to splash into-method of ultrasonic technology is as follows:
1. thin film-ultrasonic technology: take by weighing Radix Tripterygii Wilfordii lactone alcohol (Academy of Medical Sciences, Fujian Province provides), phospholipid, cholesterol, antioxidant, surfactant by recipe quantity, be dissolved in the dehydrated alcohol, be transferred in the eggplant-shape bottle, the decompression rotary evaporation is removed ethanol in 37 ℃ of waters bath with thermostatic control, on the bottle wall, form even class membrane of lipoprotein, the hydration medium that adds recipe quantity, rotation is washed film and is become suspension just, place the water-bath type Ultrasound Instrument intermittently ultrasonic, get the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor to translucent colloid solution.
2. ethanol splashes into-ultrasonic technology: take by weighing Radix Tripterygii Wilfordii lactone alcohol, phospholipid, cholesterol, antioxidant, surfactant by recipe quantity, be dissolved in the dehydrated alcohol, get the class lipoprotein solution, the class lipoprotein solution is slowly splashed in the hydration medium of recipe quantity, the jog while dripping, promptly get liposome suspension just, place water-bath type Ultrasound Instrument discontinuous ultrasonic, get the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor to translucent colloid solution.
Liposome claims lipoid bead or liquid crystal microcapsule again, is in the formed ultra micro spheroid carrier of lipoids bilayer preparation with drug encapsulation.A large amount of studies show that, liposome not only can promote the percutaneous of medicine to absorb, and produces the whole body therapeutic effect, and all right stronger local action of messenger drug deposits yields improves bioavailability, reduces toxic and side effects.Preparation capable of permeating skin so that liposomal encapsulated medicine is made can be used as drug-reservoir, produces more persistent therapeutical effect, and the material of forming liposome is the composition that exists in the organism, has no side effect, and is non-stimulated to skin.Common liposome is micron-sized lipoids bilayer structure, and size is 1～100 μ m.If in the lipoids bilayer of liposome, add suitable surfactant, then can form nanometer liposome (nanoliposomes, NL).Nanometer liposome except that particle diameter less than the conventional liposome, also have self deformation behavior of height, especially be suitable as the carrier of Transdermal absorption, mucosal drug delivery.
Gel is the suspendible of the homogeneous made by medicine and the adjuvant that can form gel or the latex glop or the semi-solid preparation of emulsion-type, with acrylic polymer is the characteristics that substrate formed gel has water-soluble base, release is fast, effect rapidly, no greasy, easily coating, non-stimulated to skin and mucosa, the skin coupling effect is good.The characteristics of attached gel agent on the basis of liposome, cause active substance to see through skin easily and improve the local organization drug level, refrigerant again, pollution-free, be easy to use, and in liposome, add after acrylic polymer forms gel, liposome is played the effect of stereoscopic stable, reduce the gathering of liposome and increased the stability of product.
Below by drug effect and toxicity test the drug action of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome exterior-applied gel provided by the invention by percutaneous drug delivery is described, and makes comparisons with the ordinary gel agent of Radix Tripterygii Wilfordii lactone alcohol.
One, the SD rat paw causes the antiinflammatory action test after the inflammation
Adopt the research method of conventional anti-inflammatory activity, get 40 of male SD rats, be divided into 4 groups at random, 10 every group.In the left back sufficient sole of the foot of Freund ' s Freund's complete adjuvant 0.1ml intradermal injection, injection adjuvant causes scorching preceding 24h percutaneous drug delivery, causes scorching back continuous use 6 days.
Test specimen: (1) blank group: normal saline; (2) Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel group (for the product of following embodiment 6): dosage is 20mg/kg (containing Radix Tripterygii Wilfordii lactone alcohol 0.4mg); (3) Radix Tripterygii Wilfordii lactone alcohol ordinary gel agent group (self-control is the product of following embodiment 1): dosage is 20mg/kg (containing Radix Tripterygii Wilfordii lactone alcohol 0.4mg); (4) positive controls (Vitalin Emulgel contains diclofenac, Novartis Pharma AG's product): dosage is 10.0mg/kg.Adopt the capillary tube amplifying method to measure the swelling degree of the sufficient sole of the foot after 6 days in medication.Swelling rate (%)=(Vt-Vo)/Vo, wherein Vo is for causing scorching front foot sole of the foot volume; Vt is the swelling volume that causes the scorching back 6 natural feet sole of the foots, the results are shown in Table 1.
Table 1 Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel causes scorching antiphlogistic effects (x ± s) to rat adjuvant
Group dosage (mg/kg) number of animals (n) causes the swelling rate (%) of scorching back 6d
The blank group--10 45.6 ± 4.5
Nanometer liposome group 0.6 10 29.2 ± 2.5
*
Non-nano liposome group 0.6 10 35.2 ± 3.7
*
Positive controls 10.0 10 31.1 ± 6.9
*
Compare with the blank group,
*P＜0.01,
*P＜0.001
Conclusion: as shown in Table 1, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel group has the obvious suppression effect to the pedal swelling due to rat Freund ' the s Freund's complete adjuvant, and its effect is better than Radix Tripterygii Wilfordii lactone alcohol ordinary gel agent group.
Two, skin acute toxicity testing:
The acute toxicity test method of medicine for external use is routinely selected 12 of healthy rabbits, and male and female half and half are divided into 3 groups at random, 4 every group.A organizes (blank group): be coated with blank gel 0.5g (method for making as described above) in skin; B organizes (intact skin group): dosage is Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel 0.5g (containing Radix Tripterygii Wilfordii lactone alcohol 10mg), is applied to skin; C organizes (damaged skin group): dosage is organized with B.24h gives 3 groups of family's rabbit back spinal column left and right sides skin depilatories with clipper and scraper before experiment, respectively is 75cm
2, A, B group keeps skin complete, and the C group is done " # " word shape cut with the sterilization syringe needle, with skin oozing of blood degree of being with 75% ethanol disinfection skin in the unhairing scope.Give each treated animal in the administration of unhairing position by above-mentioned dosage, antiseptic gauze and adhesive tape are fixed, sub-cage rearing, tried position skin with warm water cleaning after smearing medicine 24h, remove behind the medicine 1,24,48,72h to the 7 days, observe every day and the whole body poisoning manifestations of animals such as the variation of body weight, skin and hair, eye and the mucosa of record animal, breathing, central nervous system, extremity activity and 2 weeks interior death condition.As a result, smear rabbit no abnormality seen reaction behind the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel, diet, defecation, activity are all normal, and intact skin test group (A, B group) rabbit skin does not have redness, does not have dead; Damaged skin test group (C group) rabbit cutaneous scarification has redness, incrustation, does not have dead.
Three, skin irritation test:
The skin irritation test method of medicine for external use is routinely selected 8 of white healthy rabbits, and male and female half and half are divided into 2 groups at random: intact skin group and damaged skin group, 4 every group.24h gives tame rabbit back spinal column left and right sides skin depilatory with clipper and scraper before experiment, respectively is 75cm
2, the intact skin group keeps skin complete, and the damaged skin group is done " # " word shape cut with the sterilization syringe needle, with skin oozing of blood degree of being with 75% ethanol disinfection skin in the unhairing scope.Depilation district, two groups of rabbit left sides all is coated with Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel 0.5g (containing Radix Tripterygii Wilfordii lactone alcohol 10mg) during test, and depilation district in right side is coated with blank gel 0.5g and makes blank, 1 time/day, keeps 10h, successive administration 7 days at every turn.Last 1 administration after removing medicine 1,24,48,72h observes medicine-feeding part and has or not reactions such as erythema and edema.As a result, the intact skin group be coated with Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel side skin 1,24,48,72h does not all have erythema and edema occurs, and is identical with blank gel group, no erythema, no edema, vacuum response.Damaged skin group administration district and check plot skin have the cut incrustation, and not seeing has erythema, no edema, vacuum response.
Four, skin anaphylactic test:
The skin anaphylactic test method of medicine for external use is routinely got 12 of healthy guinea pigs, and male and female half and half are divided into 3 groups at random, and 4 every group, 24h gives guinea pig back spinal column left and right sides skin depilatory with clipper and scraper before experiment, respectively is 4cm * 4cm.The 1st group is the administration group, is coated with Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel, and the 2nd group is the blank group, is coated with blank gel, and the 3rd group of positive matched group gives 1%2,4-dinitro-chloro-benzene 0.2ml.Sensitization contact: depilation district, administration treated animal left side is coated with Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel 0.5g (containing Radix Tripterygii Wilfordii lactone alcohol 10mg), keeps 6h, and repeats 1 time in the 7th day and the 14th day; Blank group and positive controls operational approach are the same.Excite sensitization: after the last administration the 14th day, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel 0.5g is applied to administration treated animal right side skin, remove medicine behind the 6h, clean skin, at once observe skin allergy situation in the 1h, then in 24,48,72h observes the skin allergy situation once more, blank group and positive control group of methods are the same, result of the test is pressed the scoring of skin allergy standards of grading, calculates mean scores.As a result, administration group and matched group respectively have 1 guinea pig skin inadequate visible erythema to occur, disappear fully behind the 24h, and reaction average mark 24h is 0.1 minute, and 24～72h is 0 minute, and administration group and blank group be indifference relatively, can think that its sensitization rate is 0.10 Cavia porcelluss of positive controls excite 1～6h after the administration, there are 2 obvious erythema 2 * 2 minutes to occur, 3 the aubergine erythema occurs and have eschar to form with intermediate edema 2 * (4+2) dividing, 6 the severe erythema occurs and divide with Mild edema 6 * (3+1), total mark 38 minutes, 24h begins to disappear and is total mark 34 minutes, 48h total mark 25 minutes, it is 18 minutes that 72h still has visible erythema total mark, and the sensitization rate is 100%.
Five, the preliminarily stabilised test of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel:
1. exposure experiments to light: the accurate title, decide 10g Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel sample, is sealed in the flint glass bottle, and in 4000Lx illumination 20 days, sampling observation outward appearance was also measured percolation ratio and content in the 0th, 5,10,15,20 day.
2. humidity is to the influence of stability: the accurate title, decide 10g Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel sample, is respectively 75% and 92.5% in relative humidity, and placement is 20 days in 25 ℃ of sealing vessel of constant temperature, and timing sampling is measured every index.
3. temperature is to the influence of stability: the accurate title, decide 10g Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel sample, is sealed in the vial, and respectively at placement in 20,40,60 ℃ of thermostatic driers 20 days, timing sampling was measured every index.
The result shows that illumination and high humility are little to stability influence, and the gel character is not seen obvious change in the time of 20,40 ℃, and content of dispersion is no change also.Gel darkens in the time of 60 ℃, and produces precipitation, and percolation ratio reaches 25.3% in the time of 20 days.Illustrate that temperature can cause the variation of matrix material, the bigger influence of envelop rate generation to medicine notes in producing use.
Above-mentioned experimental result shows that Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel provided by the invention absorbs by percutaneous dosing, and drug effect is remarkable, and antiinflammatory action is preferably arranged; Toxic and side effects is little, and, damaged skin complete to rabbit all do not have the acute absorption toxicity of skin,, damaged skin nonirritant complete to rabbit and guinea pig skin do not produced sensitization; Product stability is good, illustrates that Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel is safe external preparation; Preparation technology is simple, is fit to industrialized mass production.
Set forth technical scheme of the present invention below by embodiment.
The specific embodiment
The preparation of embodiment 1, the agent of Radix Tripterygii Wilfordii lactone alcohol ordinary gel:
Take by weighing acrylic polymer material carbomer (product of Bandung company limited) 3g, with about 90ml distilled water swelling, dropping 4.5g triethanolamine is transparent to gel, gets the about 100g of the blank gel of 3% carbomer.Other gets Radix Tripterygii Wilfordii lactone alcohol 2g (product that the Academy of Medical Sciences, Fujian Province provides), is dissolved in a small amount of dehydrated alcohol, adds in the above-mentioned gel-type vehicle, and equidirectional stirring and evenly mixing promptly gets 2% Radix Tripterygii Wilfordii lactone alcohol ordinary gel agent.
Embodiment 2,
One, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor (thin film-ultrasonic technology):
Take by weighing Radix Tripterygii Wilfordii lactone alcohol 200mg, soybean lecithin 4g, cholesterol lg, vitamin E 0.2g, sodium deoxycholate 0.2g, be dissolved in the 20ml dehydrated alcohol, be transferred in the eggplant-shape bottle of 1000ml, the decompression rotary evaporation is removed ethanol in 37 ℃ of waters bath with thermostatic control, forms even class membrane of lipoprotein on the bottle wall, add about 15ml water, rotate and wash film one-tenth suspension just, place the water-bath type Ultrasound Instrument intermittently ultrasonic, get Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 20g to translucent colloid solution;
Two, the preparation of blank gel;
Take by weighing acrylic polymer material carbomer (product of Bandung company limited) 5.4g, with about 167ml distilled water swelling, dropping 7.5g triethanolamine is transparent to gel, gets the blank gel 180g of 3% carbomer.
Three, the preparation of gel:
Nanometer liposome turbid liquor 20g is added in the blank gel-type vehicle of 180g, and equidirectional stirring and evenly mixing promptly gets 0.1% Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
Embodiment 3,
One, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor (ethanol splashes into-ultrasonic technology):
Take by weighing Radix Tripterygii Wilfordii lactone alcohol 200mg, Ovum Gallus domesticus Flavus lecithin 3g, cholesterol 0.75g, ethyl hydroxybenzoate 0.15g, sodium cholate 0.15g, be dissolved in the 20ml dehydrated alcohol, get the class lipoprotein solution, the class lipoprotein solution is slowly splashed in the phosphate buffer of about 30mlpH7.4, the jog while dripping promptly gets liposome suspension just, place water-bath type Ultrasound Instrument discontinuous ultrasonic, get Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 50g to translucent colloid solution;
Two, the preparation of blank gel;
Take by weighing carbomer 0.6g, with about 27ml distilled water swelling, dropping 2.4g triethanolamine is transparent to gel, gets the blank gel 30g of 2% carbomer.
Three, the preparation of gel:
Nanometer liposome turbid liquor 50g is added in the blank gel-type vehicle of 30g, and equidirectional stirring and evenly mixing promptly gets 0.25% Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
Embodiment 4,
One, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor (ethanol splashes into-ultrasonic technology):
Take by weighing Radix Tripterygii Wilfordii lactone alcohol 400mg, soybean lecithin 6g, cholesterol 1.5g, vitamin E 0.3g, sodium cholate 0.3g, be dissolved in the 20ml dehydrated alcohol, get the class lipoprotein solution, the class lipoprotein solution is slowly splashed in about 22ml water, the jog while dripping, promptly get liposome suspension just, place water-bath type Ultrasound Instrument discontinuous ultrasonic, get Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 50g to translucent colloid solution;
Two, the preparation of blank gel;
Take by weighing carbomer 2g, with about 38ml distilled water swelling, dropping 10g triethanolamine is transparent to gel, gets the blank gel 50g of 4% carbomer.
Three, the preparation of gel:
Nanometer liposome turbid liquor 50g is added in the blank gel-type vehicle of 50g, and equidirectional stirring and evenly mixing promptly gets 0.4% Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
Embodiment 5,
One, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor (thin film-ultrasonic technology):
Take by weighing Radix Tripterygii Wilfordii lactone alcohol 1g, Ovum Gallus domesticus Flavus lecithin 20g, cholesterol 5g, propylparaben 1g, sodium deoxycholate 1g, be dissolved in the 100ml dehydrated alcohol, be transferred in the eggplant-shape bottle, the decompression rotary evaporation is removed ethanol in 37 ℃ of waters bath with thermostatic control, forms even class membrane of lipoprotein on the bottle wall, the phosphate buffer that adds about 170mlpH7.4, rotate and wash film one-tenth suspension just, place the water-bath type Ultrasound Instrument intermittently ultrasonic, get Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 200g to translucent colloid solution;
Two, the preparation of blank gel;
Take by weighing carbomer 3g, with about 167ml distilled water swelling, dropping 6g triethanolamine is transparent to gel, gets the blank gel 100g of 3% carbomer.
Three, the preparation of gel:
Nanometer liposome turbid liquor 200g is added in the blank gel-type vehicle of 100g, and equidirectional stirring and evenly mixing promptly gets 0.33% Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
Embodiment 6,
One, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor (ethanol splashes into-ultrasonic technology):
Take by weighing Radix Tripterygii Wilfordii lactone alcohol 4g, soybean lecithin 20g, cholesterol 4g, vitamin e1 g, sodium deoxycholate 1g, be dissolved in the 60ml dehydrated alcohol, get the class lipoprotein solution, the class lipoprotein solution is slowly splashed in about 30ml water, the jog while dripping, promptly get liposome suspension just, place water-bath type Ultrasound Instrument discontinuous ultrasonic, get Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 120g to translucent colloid solution;
Two, the preparation of blank gel;
Take by weighing carbomer 2g, expand with about 74ml is water-soluble, dropping 4g triethanolamine is transparent to gel, gets the blank gel 80g of 2.5% carbomer.
Three, the preparation of gel:
Nanometer liposome turbid liquor 120g is added in the blank gel of 80g, and equidirectional stirring and evenly mixing promptly gets 2% Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
The mensuration of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome particle diameter: the nanometer liposome turbid liquor of getting above-mentioned prepared is an amount of, behind the dilute with water, puts the multi-functional Zeta potential Particle Size Analyzer of Zetapals and measures particle diameter, result such as table 2:
Table 2 Radix Tripterygii Wilfordii lactone alcohol nanometer liposome particle size determination result
| Batch particle diameter (nm) | ???? x±s |
| Embodiment 2 samples 110 embodiment 3 samples 156 embodiment 4 samples 182 embodiment 5 samples 128 embodiment 6 samples 190 | ? ? ????153.2±34.3 |
Claims (7)
1, a kind of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation is characterized in that the gel of being made by the compositions of following weight percentage ratio: Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor 10～70% and blank gel 90～30%; The weight percent content of Radix Tripterygii Wilfordii lactone alcohol is 0.1～2.0% in total gel.
2, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation as claimed in claim 1 is characterized in that described Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor is to be made by following weight percentages: all the other are hydration medium for Radix Tripterygii Wilfordii lactone alcohol 0.7～4.2%, phosphatidase 11 4～64%, cholesterol 3.5～16%, antioxidant 0.7～3.2%, surfactant 0.7～3.2%.
3, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation as claimed in claim 1 is characterized in that described blank gel is to be made by following weight percentages: 1～4% acrylic polymer, 1.4～5.6% weak organic bases, all the other are water.
4, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation as claimed in claim 2, it is characterized in that described phospholipid is soybean lecithin or Ovum Gallus domesticus Flavus lecithin, described antioxidant is vitamins or parabens, described surfactant is sodium cholate or sodium deoxycholate, and described hydration medium is phosphate buffer or water.
5, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation as claimed in claim 2 is characterized in that described phospholipid is soybean lecithin, and described antioxidant is vitamin E, and described surfactant is a sodium deoxycholate, and described hydration medium is a water.
6, Radix Tripterygii Wilfordii lactone alcohol nanometer liposome external preparation as claimed in claim 3 is characterized in that described acrylic polymer is a carbomer series, and described weak organic base is a triethanolamine.
7, the preparation method of Radix Tripterygii Wilfordii lactone alcohol nanometer plastid exterior-applied gel as claimed in claim 1, it is characterized in that carrying out as follows: one, the preparation of Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor: take by weighing Radix Tripterygii Wilfordii lactone alcohol, phospholipid, cholesterol, antioxidant, surfactant by recipe quantity, be dissolved in the dehydrated alcohol, with thin film-ultrasonic technology or ethanol splash into-ultrasonic technology adds the hydration medium of recipe quantity, the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor; Two, the preparation of blank gel: with recipe quantity acrylic polymer water swelling, organic base is transparent to gel a little less than dripping, the white gel of promptly having leisure; Three, the preparation of gel: by recipe quantity the Radix Tripterygii Wilfordii lactone alcohol nanometer liposome turbid liquor that makes is added in the blank gel, equidirectional stirring and evenly mixing promptly gets Radix Tripterygii Wilfordii lactone alcohol nanometer liposome gel.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410052121 CN1634033A (en) | 2004-11-10 | 2004-11-10 | Triptolide nano lipsome gelling agent of external use and its preparation method |
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|---|---|---|---|
| CN 200410052121 CN1634033A (en) | 2004-11-10 | 2004-11-10 | Triptolide nano lipsome gelling agent of external use and its preparation method |
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|---|---|---|---|---|
| CN100411609C (en) * | 2006-11-27 | 2008-08-20 | 西北农林科技大学 | Nano-emulsion drug of triperygium wilfordii polycoride and preparation method thereof |
| CN101239040B (en) * | 2008-03-11 | 2010-06-02 | 中国药科大学 | Celastrol liposome and preparation thereof |
| CN101015551B (en) * | 2006-02-08 | 2010-08-04 | 福建省医学科学研究所 | Preparing method of triptolide stereoscopic stable liposome nano granule |
| CN101991585A (en) * | 2009-08-25 | 2011-03-30 | 福建省医学科学研究所 | Percutaneous absorption film coating agent for treating rheumatoid arthritis and preparation method thereof |
| CN102085199A (en) * | 2009-12-08 | 2011-06-08 | 福建省医学科学研究所 | Percutaneous absorption biological patch for treating rheumatoid arthritis and preparing method thereof |
| CN103393598A (en) * | 2013-08-06 | 2013-11-20 | 南京中医药大学 | Triptolide liposome preparation for treatment of small cell lung cancer and preparation method thereof |
| CN106924176A (en) * | 2017-03-20 | 2017-07-07 | 荆楚理工学院 | A kind of TAM flexible nano-liposomes gel and preparation method thereof |
| CN106975075A (en) * | 2016-01-18 | 2017-07-25 | 云南白药集团无锡药业有限公司 | Papain liposome gel Preparation method and use |
| CN107149593A (en) * | 2017-04-11 | 2017-09-12 | 中国人民解放军第三医院八临床部 | Celastrol flexible lipidosome, gel and preparation method thereof |
| CN108721679A (en) * | 2016-02-03 | 2018-11-02 | 丁永新 | A kind of anti-inflammatory antibacterial medical dressing |
| CN109528693A (en) * | 2018-12-20 | 2019-03-29 | 武汉科福新药有限责任公司 | A kind of rapamycin cataplasm and preparation method thereof |
| CN112891270A (en) * | 2021-01-29 | 2021-06-04 | 洪怡 | Cosmetic composition and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101015551B (en) * | 2006-02-08 | 2010-08-04 | 福建省医学科学研究所 | Preparing method of triptolide stereoscopic stable liposome nano granule |
| CN100411609C (en) * | 2006-11-27 | 2008-08-20 | 西北农林科技大学 | Nano-emulsion drug of triperygium wilfordii polycoride and preparation method thereof |
| CN101239040B (en) * | 2008-03-11 | 2010-06-02 | 中国药科大学 | Celastrol liposome and preparation thereof |
| CN101991585A (en) * | 2009-08-25 | 2011-03-30 | 福建省医学科学研究所 | Percutaneous absorption film coating agent for treating rheumatoid arthritis and preparation method thereof |
| CN101991585B (en) * | 2009-08-25 | 2014-04-16 | 福建省医学科学研究院 | Percutaneous absorption film coating agent for treating rheumatoid arthritis and preparation method thereof |
| CN102085199A (en) * | 2009-12-08 | 2011-06-08 | 福建省医学科学研究所 | Percutaneous absorption biological patch for treating rheumatoid arthritis and preparing method thereof |
| CN102085199B (en) * | 2009-12-08 | 2014-05-28 | 福建省医学科学研究院 | Percutaneous absorption biological patch for treating rheumatoid arthritis and preparing method thereof |
| CN103393598A (en) * | 2013-08-06 | 2013-11-20 | 南京中医药大学 | Triptolide liposome preparation for treatment of small cell lung cancer and preparation method thereof |
| CN106975075A (en) * | 2016-01-18 | 2017-07-25 | 云南白药集团无锡药业有限公司 | Papain liposome gel Preparation method and use |
| CN108721679A (en) * | 2016-02-03 | 2018-11-02 | 丁永新 | A kind of anti-inflammatory antibacterial medical dressing |
| CN108721679B (en) * | 2016-02-03 | 2020-11-20 | 唐山市博世德医疗器械有限公司 | Anti-inflammatory and antibacterial medical dressing |
| CN106924176A (en) * | 2017-03-20 | 2017-07-07 | 荆楚理工学院 | A kind of TAM flexible nano-liposomes gel and preparation method thereof |
| CN106924176B (en) * | 2017-03-20 | 2020-08-11 | 荆楚理工学院 | Tamoxifen flexible nano liposome gel and preparation method thereof |
| CN107149593A (en) * | 2017-04-11 | 2017-09-12 | 中国人民解放军第三医院八临床部 | Celastrol flexible lipidosome, gel and preparation method thereof |
| CN109528693A (en) * | 2018-12-20 | 2019-03-29 | 武汉科福新药有限责任公司 | A kind of rapamycin cataplasm and preparation method thereof |
| CN109528693B (en) * | 2018-12-20 | 2022-03-01 | 武汉科福新药有限责任公司 | Rapamycin cataplasm and preparation method thereof |
| CN112891270A (en) * | 2021-01-29 | 2021-06-04 | 洪怡 | Cosmetic composition and preparation method and application thereof |
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