CN104173285A - Preparation method for triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent and application to target hypertrophic scars - Google Patents
Preparation method for triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent and application to target hypertrophic scars Download PDFInfo
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Abstract
The invention discloses a preparation method for a triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent and application to target hypertrophic scars. The triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent is composed of the following compositions in percent by weight: 0.05%- 0.5% of triamcinolone acetonide acetate, 0.5%- 10% of phosphatide, and 0.2%- 50% of a softener. The prepared triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent has the average particle size of 50-500 nm. By optimizing the above ratio, the medicine can be relatively highly concentrated at a scar skin nidus area, and the composition ratio comprises, in percent by weight, 0.1% of triamcinolone acetonide, 4% of phosphatide, and 0.77% of sodium cholate. The prepared triamcinolone acetonide acetate ultradeformable nanometer lipid vesicle spraying agent solves many problems caused by multi-point injection in scar and triamcinolone acetonide external application, and is substantial in the hypertrophic-scar targeting effect.
Description
Technical field
The present invention relates to technical field of medicine, is a kind of preparation method and targeting hypertrophic cicatrix purposes thereof of triamcinolone acetonide acetate flexible nano lipid vesicles spray.
Background technology
The pathological characters of hypertrophic cicatrix is epidermis and dermal fibroblast hyper-proliferative, and collagen deposits in a large number, is difficult to absorbed by body or reinvent, and causes the torment of patient's long term body and spirit with painful.At present, topical in cicatrix, comprises multi-point injection and outer painting triamcinolone acetonide in cicatrix, is main non-operative treatment.But multi-point injection in cicatrix, exists that hurt like hell, dosage are inaccurate, the unequal shortcoming of drug diffusion; And the outer triamcinolone acetonide that is coated with highly lipophilic does not have again good transdermal effect.Therefore, develop a kind of painless, steady lasting deep skin targeting preparation, there is urgent clinical practice meaning.
German scholar Cevc G adds sodium cholate in the early 1990s in last century in preparation lipid vesicles, surprisingly prepares flexible nano lipid vesicles, i.e. carrier.Series of studies finds that it has highly flexible, under the ordering about of skin hydration power, unexpectedly can be out of shape at most through than self horny layer fenestra of little 5 times, enters deep skin.Triamcinolone acetonide acetate is a kind of glucocorticoid, has the multiple pharmacological effect such as antiinflammatory, antiallergic and Immunosuppression.CevcG is conceived to its antiinflammatory action, and the triamcinolone acetonide acetate flexible nano lipid vesicles of same dose is found in zoopery checking, and its anti-inflammatory effect is the more than 10 times of market milk unguentum.
We introduce flexible nano lipid vesicles and treat hypertrophic cicatrix for triamcinolone acetonide acetate, attempt a kind of painless, steady lasting deep skin targeting preparation of exploitation, medicine enters skin to greatest extent, and concentrate in a large number, but to the greatest extent at utmost reduce the possibility that enters blood in the epidermis of Skin scar lesions position and skin corium.
Spray is the better dosage form of current skin large area administration, and its safety is good, and preparation and easy to use.Its tool has the following advantages: (1) can accurately control dosage with quantitative valve; (2) the thing grain of ejection is thinner, and in the good dispersion degree of skin, medicinal liquid is difficult for running off; (3) scope of application is wider, can be used for skin, mucosa and wound surface.
The preparation of triamcinolone acetonide acetate flexible nano lipid vesicles abroad has been reported, and still, the preparation of triamcinolone acetonide acetate nano-lipid vesicle spray has no report.In addition, triamcinolone acetonide acetate nano-lipid vesicle also has no report for Skin scar targeting.
Summary of the invention
The object of the invention is preferably a kind ofly can increase the flexible nano lipid vesicles proportioning that triamcinolone acetonide acetate concentrates in Skin scar focus region height to greatest extent, and is prepared into spray.
Triamcinolone acetonide acetate flexible nano lipid vesicles spray, comprise triamcinolone acetonide acetate active component and prepare the flexible nano lipid vesicles medicinal adjuvant of accepting used, it is characterized in that proportioning is, the percentage by weight of triamcinolone acetonide acetate is 0.05%～0.5%, prepares flexible nano lipid vesicles adjuvant used and comprises phospholipid and softening agents.Wherein the percentage by weight of phospholipid is 0.5%～10%, is selected from soybean lecithin, Ovum Gallus domesticus Flavus lecithin, synthetic phospholipid phatidylcholine, can select wherein one or more simultaneously; The percentage by weight of softening agents is 0.2%～50%, is selected from sodium cholate, ethanol, can select wherein one or both simultaneously.
The fenestra of keratodermatitis under irriate, is not generally below 10nm.Smear or spray in the situations such as medicine irritation, the fenestra of keratodermatitis can increase to 20～40nm.Flexible nano lipid vesicles has the mechanism of strong short saturating effect, and just under the ordering about by skin hydration power, deformables, through than self horny layer fenestra of little 5 times, enter deep skin at most unexpectedly.Therefore, the particle diameter of flexible nano lipid vesicles, for the drug distribution in Skin scar, has significant regulating and controlling effect.The present invention's discovery, the mean diameter of described spray must be controlled at 50～500nm, and triamcinolone acetonide has better epidermis and the local targeting effect of concentrating of skin corium just now.
A kind of triamcinolone acetonide acetate flexible nano lipid vesicles spray for the treatment of hypertrophic cicatrix disease provided by the present invention, can relative altitude concentrate medicine in the optimization prescription proportioning in Skin scar focus region, its component comprises triamcinolone acetonide active component and prepares flexible nano lipid vesicles adjuvant used.Wherein the percentage by weight of triamcinolone acetonide acetate is 0.1%, and the percentage by weight of phospholipid is 4%, and the percentage by weight of sodium cholate is 0.77%.
Spray preparation method provided by the present invention, step is as follows.
(1) by the phospholipid in described spray, triamcinolone acetonide acetate in eggplant-shape bottle, add chloroform-methanol (1: 1, v/v) mixed solvent 30ml, in 37 DEG C of waters bath with thermostatic control, water pump evaporation under reduced pressure removed organic solvent, form the even lipoids thin film of one deck, nitrogen injection at bottle inwall;
(2) aqueous solution of sodium cholate in described spray is added in the lipoids thin film that (1) make, film 2h is washed in rotation;
(3) flexible nano lipid vesicles suspension probe-type under ice-water bath condition of being prepared by (2) is interrupted ultrasonic 15min, and 0.22 μ m filtering with microporous membrane, prepares uniform flexible nano lipid vesicles.
(4) the flexible nano lipid vesicles of being prepared by (3) is mixed and made into triamcinolone acetonide acetate flexible nano lipid vesicles spray with certain proportioning distilled water.Steam sterilization, filtration, aseptic subpackaged to aerosol container.
The mean diameter of the triamcinolone acetonide acetate flexible nano lipid vesicles spray that the present invention makes is 100～200nm, and envelop rate is (67.04 ± 3.77) %.
The triamcinolone acetonide acetate flexible nano lipid vesicles spray that the present invention makes is respectively common nano-lipid vesicle and commercially available emulsifiable paste 2.20 and 4.43 times at the 12h accumulation transit dose of in vitro hypertrophic cicatrix skin, and the hold-up of administration 12h targeting hypertrophic cicatrix epidermis and corium is respectively 5.44 and 7.72 times of commercially available emulsifiable paste.
The made flexible lipid nanometer vesicle of the triamcinolone acetonide acetate spray of the present invention has solved the poor problem of triamcinolone acetonide transdermal effect of outer painting highly lipophilic, and the feature of the slow and targeting release of active ingredients of flexible lipid vesicles uniqueness, make the effect of triamcinolone acetonide lasting, remarkable to the therapeutic effect of hypertrophic cicatrix.
Brief description of the drawings
Fig. 1 is triamcinolone acetonide acetate flexible nano lipid vesicles spray electromicroscopic photograph (× 20000).
Fig. 2 is 0.1% triamcinolone acetonide acetate flexible nano lipid vesicles spray and 0.1% triamcinolone acetonide nano-lipid vesicle, 0.1% triamcinolone acetonide solution and the comparison of commercially available 0.1% Kenac Cream in vitro cicatrix Penetration Signature.
Fig. 3 is 0.1% triamcinolone acetonide acetate flexible nano lipid vesicles spray and the triamcinolone acetonide medicine retention amount comparison in body scar cuticle after coating different time of commercially available 0.1% Kenac Cream.
Fig. 4 is 0.1% triamcinolone acetonide acetate flexible nano lipid vesicles spray and the triamcinolone acetonide medicine retention amount comparison in body cicatrix corium after coating different time of commercially available 0.1% Kenac Cream.
Detailed description of the invention
Describe the present invention below in conjunction with embodiment, but the present invention is not construed as limiting.
The phospholipid proportioning screening of embodiment 1 triamcinolone acetonide acetate flexible nano lipid vesicles spray
Write out a prescription a component proportion (w/w/%) and dosage:
Write out a prescription two component proportions (w/w/%) and dosage:
Write out a prescription three component proportions (w/w/%) and dosage:
preparation method
Quantitatively take phospholipid, triamcinolone acetonide acetate in above-mentioned each prescription and, in eggplant-shape bottle, add chloroform-methanol (1: 1, v/v) mixed solvent 30ml, in 37 DEG C of waters bath with thermostatic control, water pump evaporation under reduced pressure removed organic solvent, forms the even lipoids thin film of one deck, nitrogen injection at bottle inwall.Add the aqueous solution of the sodium cholate of the content of writing out a prescription, film 2h is washed in rotation, obtains flexible nano lipid vesicles suspension.Under ice-water bath condition, probe-type is interrupted ultrasonic 15min, and 0.22 μ m filtering with microporous membrane, prepares uniform flexible nano lipid vesicles.Flexible nano lipid vesicles and corresponding proportioning distilled water are mixed and made into triamcinolone acetonide acetate flexible nano lipid vesicles spray.Steam sterilization, filtration, aseptic subpackaged to aerosol container.
morphologic observation
Draw each formula preparation triamcinolone acetonide acetate flexible nano lipid vesicles spray a little, drip in having on the copper mesh of supporting film, the phosphotungstic acid negative staining of slightly dry rear use 3%, filter paper is inhaled copper mesh edge unnecessary liquid, slightly dry, transmission electron microscope observing.Fig. 1 is triamcinolone acetonide acetate flexible nano lipid vesicles spray electromicroscopic photograph (× 20000), Fig. 1 is visible, each prescription makes triamcinolone acetonide acetate flexible nano lipid vesicles spray and is all ball or elliptical shape, and prescription one, two, the three lipid vesicles size of preparing gained are all at 100～200nm.
envelop rate comparison
Get the triamcinolone acetonide acetate flexible nano lipid vesicles spray 1.5ml of above-mentioned each formula preparation in centrifuge tube, 8 × 10
5r/min, 4 DEG C of centrifugal 2h.Get supernatant, HPLC method is measured free drug amount C1.The triamcinolone acetonide acetate flexible nano lipid vesicles spray 1.5ml that gets respectively in addition above-mentioned each formula preparation, adds appropriate 20%TritonX-100, and HPLC method is measured medicine total amount C
2, envelop rate=(C
2-C
1)/C
2× 100%.
assay
Chromatographic condition: chromatographic column is Diamonsil C
18post (4.6mm × 250mm, m), mobile phase is methanol-water (70: 30) to 5 μ, 25 DEG C of column temperatures, flow velocity 1.0ml/min, detects wavelength 240nm, sampling volume 20 μ l.
The preparation of standard curve: precision takes reference substance 25mg, is placed in 50ml volumetric flask, adds methanol 35ml and dissolves, and is diluted with water to scale, shakes up, as storing solution.Adopt respectively mobile phase, diffusion cell acceptable solution, the blank skin histology homogenate dilution of cicatrix, prepare corresponding standard curve.Taking average peak area A as vertical coordinate, reference substance concentration C is that abscissa carries out linear regression, and lipid vesicles entrapment efficiency determination is A=44826C+3246.6 (n=5, r=0.9999) with standard curve equation, and the range of linearity is 0.1～50 μ g/ml.
The envelop rate that envelop rate experiment records prescription one triamcinolone acetonide acetate flexible nano lipid vesicles is (67.04 ± 3.77) %, and the envelop rate of prescription two and prescription three is respectively (44.68 ± 3.24) %, (68.31 ± 4.57) %.
Along with the percentage by weight of phospholipid in prescription increases, the envelop rate of flexible nano lipid vesicles increases, and still, phospholipid percentage by weight is higher than after 4%, and envelop rate increases and be not obvious.To sum up, the phospholipid of flexible nano lipid vesicles prescription selects 4%.
The sodium cholate proportioning screening of embodiment 2 triamcinolone acetonide acetate flexible nano lipid vesicles sprays
Write out a prescription a component proportion (w/w/%) and dosage:
Write out a prescription two component proportions (w/w/%) and dosage:
Write out a prescription three component proportions (w/w/%) and dosage:
preparation method
Quantitatively take phospholipid, triamcinolone acetonide acetate in above-mentioned each prescription and, in eggplant-shape bottle, add chloroform-methanol (1: 1, v/v) mixed solvent 30ml, in 37 DEG C of waters bath with thermostatic control, water pump evaporation under reduced pressure removed organic solvent, forms the even lipoids thin film of one deck, nitrogen injection at bottle inwall.Add the aqueous solution of the sodium cholate of the content of writing out a prescription, film 2h is washed in rotation, obtains flexible nano lipid vesicles suspension.Under ice-water bath condition, probe-type is interrupted ultrasonic 15min, and 0.22 μ m filtering with microporous membrane, prepares uniform flexible nano lipid vesicles.Flexible nano lipid vesicles and corresponding proportioning distilled water are mixed and made into triamcinolone acetonide acetate flexible nano lipid vesicles spray.Steam sterilization, filtration, aseptic subpackaged to aerosol container.
morphologic observation
Draw each formula preparation triamcinolone acetonide acetate flexible nano lipid vesicles spray a little, drip in having on the copper mesh of supporting film, the phosphotungstic acid negative staining of slightly dry rear use 3%, filter paper is inhaled copper mesh edge unnecessary liquid, slightly dry, transmission electron microscope observing.Result demonstration, each prescription makes triamcinolone acetonide acetate flexible nano lipid vesicles spray and is all ball or elliptical shape, and prescription one, two, the three lipid vesicles size of preparing gained are all at 100～200nm.
morphotropism is investigated
Observe under external pressure, it is the performance of 0.06 μ m microporous filter membrane through aperture that each prescription makes the distortion of triamcinolone acetonide acetate flexible nano lipid vesicles spray.First record 5ml distilled water and see through microporous filter membrane required time, then record each prescription and make triamcinolone acetonide acetate flexible nano lipid vesicles spray 5ml through the required time of same filter membrane, calculate relative transmission rates P=Vtf/Vwater × 100% with this.Investigate each prescription under certain pressure and make the relative transmission rates of triamcinolone acetonide acetate flexible nano lipid vesicles spray.Each prescription morphotropism result is as table 1, and visible, the morphotropism of made spray increases with the increase of sodium cholate content, but that the relative speed of prescription three is compared prescription one increase is not obvious.
The each prescription of table 1 make spray morphotropism experimental result (n=4,
)
* P < 0.05, with prescription two contrasts
envelop rate comparison
Get the triamcinolone acetonide acetate flexible nano lipid vesicles spray 1.5ml of above-mentioned each formula preparation in centrifuge tube, 8 × 10
5r/min, 4 DEG C of centrifugal 2h.Get supernatant, HPLC method is measured free drug amount C
1.The triamcinolone acetonide acetate flexible nano lipid vesicles spray 1.5ml that gets respectively in addition above-mentioned each formula preparation, adds appropriate 20%TritonX-100, and HPLC method is measured medicine total amount C
2, envelop rate=(C
2-C
1)/C
2× 100%.
The envelop rate that envelop rate experiment records prescription one triamcinolone acetonide acetate flexible nano lipid vesicles is (67.04 ± 3.77) %, and the envelop rate of prescription two and prescription three is respectively (71.15 ± 2.04) %, (51.81 ± 1.52) %.
Along with the percentage by weight of sodium cholate in prescription increases, the morphotropism of flexible nano lipid vesicles increases, and still, envelop rate but reduces.To sum up, the sodium cholate of flexible nano lipid vesicles prescription selects 0.77%.
1,2 results in conjunction with the embodiments, when prescription proportioning is 4% phospholipid, 0.77% sodium cholate, spray particle diameter, envelop rate and morphotropism are all better.
The in vitro Skin scar release experiment of embodiment 3
the preparation of skin
Choose that the course of disease 1 year is above, local scar is more smooth,, the hypertrophic cicatrix patient that need excision above without ulceration, area 3cm × 3cm, preoperative informed consent.Operation is taken off after Skin scar, removes subcutaneous fat, clean with normal saline rinsing, and-20 DEG C of preservations are for subsequent use.
permeability test
The Franz diffusion cell that adopts improvement, is fixed on skin between supply pool and acceptance pool, and stratum corneum side is to supply pool, and effectively infiltrating area is 0.952cm
2.Supply pool is put into respectively prescription one and is made 0.1% triamcinolone acetonide acetate flexible nano lipid vesicles spray, 0.1% triamcinolone acetonide acetate nano-lipid vesicle, 0.1% triamcinolone acetonide solution, the each 0.5g of commercially available triamcinolone acetonide acetate emulsifiable paste, and acceptance pool adds the normal saline 4.2ml of 20% ethanol.Bath temperature is (37.0 ± 0.5) DEG C, magnetic agitation speed is 300r/min, respectively at 0,2,4,6,9,12h extracts whole acceptable solutions, supplement the fresh acceptable solution of equal-volume equality of temperature simultaneously, HPLC method is measured the content of triamcinolone acetonide in acceptable solution, and presses document and calculate accumulation infiltration capacity Q (μ g/cm
2) and transdermal flow J (μ gcm
-2h
-1).
skin Chinese medicine hold-up
After permeability test 12h, diffusion position skin is wiped to unnecessary medicine gently with the cotton ball that is moistened with methanol.Precise weighing skin, is cut into fragment, adds the normal saline 5ml of 20% ethanol, homogenate 5min in refiner, 1 × 10
4the centrifugal 10min of r/min.Get homogenate 200 μ l, be placed in 10ml centrifuge tube, add 70% methanol 200 μ l, mix, add ethyl acetate-normal hexane (4: 1) 2ml, vortex 2min, leave standstill 10min, the centrifugal 10min of 3000r/min, draws upper organic phase in 10ml cone end test tube.In above-mentioned tool plug test tube, add again ethyl acetate-normal hexane (4: 1) 2.0ml, carry out reextraction.Twice extract merged, and 40 DEG C of water-baths, volatilize under nitrogen current, and 200 μ l mobile phases are redissolved, and 1 × 10
4the centrifugal 10min of r/min, filters, and HPLC method is measured the content of triamcinolone acetonide in supernatant.
It is A=44713C-71.065 (n=5, r=0.9999) that HPLC records acceptable solution standard curve equation, and the range of linearity is 0.1～10 μ g/ml; Skin scar homogenate mensuration is A=38763C+29712 (n=6, r=0.9987) with standard curve equation, and the range of linearity is 1～100 μ g/ml.
The in vitro Skin scar transdermal characteristic of different Cinacort Spans, is shown in Fig. 2.The in vitro Skin scar transdermal flow of different Cinacort Spans and skin are detained dose, in table 2.
Fig. 2 and table 2 are visible, and the 12h accumulation transit dose of triamcinolone acetonide acetate flexible nano lipid vesicles spray is (7.84 ± 0.99) μ g/cm
2, be respectively 2.20 and 4.43 times (P < 0.05) of common nano-lipid vesicle and commercially available emulsifiable paste.
The in vitro Skin scar transdermal flow of table 2 Cinacort Span and skin delay dose (n=4,
)
* P < 0.05, with 0.1% Kenac Cream contrast
Embodiment 4 targeting hypertrophic cicatrix tests
Choose that the course of disease 1 year is above, local scar is more smooth,, the hypertrophic cicatrix patient that need excision above without ulceration, area 30cm × 10cm, preoperative informed consent.Before resection operation 12h, Skin scar is divided to 4 of lateral symmetry, every sides, totally 8 1.5cm × 1.5cm regions, interval 3cm at least between each region.Points two groups, to write out a prescription for one group and one make triamcinolone acetonide acetate flexible nano lipid vesicles spray 0.3g, another is organized little Glass rod decrement method and smears commercially available song and smear Kenac Cream 0.3g.Front 2 respectively at operation, 4,12h coating, remain 2 regions in contrast.For building aquation force environment, medicine-feeding part does not give wrapping.After operation, cut rapidly each coating Skin scar region, wipe gently unnecessary medicine with the cotton ball that is moistened with methanol respectively, remove subcutaneus adipose tissue, the epidermal area of hot plate method separate skin and skin corium, by each layer of skin precise weighing, be cut into fragment, add the normal saline 5ml of 20% ethanol, homogenate 5min in refiner, 1 × 10
4the centrifugal 10min of r/min.Get homogenate 200 μ l, be placed in 10ml centrifuge tube, add 70% methanol 200 μ l, mix, add ethyl acetate-normal hexane (4: 1) 2ml, vortex 2min, leave standstill 10min, the centrifugal 10min of 3000r/min, draws upper organic phase in 10ml cone end test tube.In above-mentioned tool plug test tube, add again ethyl acetate-normal hexane (4: 1) 2.0ml, carry out reextraction.Twice extract merged, and 40 DEG C of water-baths, volatilize under nitrogen current, and 200 μ l mobile phases are redissolved, and 1 × 10
4the centrifugal 10min of r/min, filters, and HPLC method is measured the content of triamcinolone acetonide in each layer of supernatant of skin.
After coating, the medicine retention quantitative change of triamcinolone acetonide in different time scar cuticle, corium, is shown in respectively Fig. 3 and Fig. 4.Fig. 3 and Fig. 4 are visible, and after coating, in each time point scar cuticle and skin corium, triamcinolone acetonide acetate flexible nano lipid vesicles spray has all significantly strengthened the delay (P < 0.05) of triamcinolone acetonide.Wherein, coating 12h, triamcinolone acetonide acetate flexible nano lipid vesicles spray epidermis and corium hold-up are respectively 5.44 and 7.72 times of commercially available emulsifiable paste.
Claims (6)
1. a triamcinolone acetonide acetate flexible nano lipid vesicles spray, comprise triamcinolone acetonide acetate active component and prepare flexible nano lipid vesicles medicinal acceptable adjuvant used, it is characterized in that proportioning is, the percentage by weight of triamcinolone acetonide acetate is 0.05%～0.5%, prepares flexible nano lipid vesicles adjuvant used and comprises phospholipid and softening agents.Wherein the percentage by weight of phospholipid is 0.5%～10%, is selected from soybean lecithin, Ovum Gallus domesticus Flavus lecithin, synthetic phospholipid phatidylcholine, can select wherein one or more simultaneously; The percentage by weight of softening agents is 0.2%～50%, is selected from sodium cholate, ethanol, can select wherein one or both simultaneously.
2. triamcinolone acetonide acetate flexible nano lipid vesicles spray according to claim 1, the mean diameter that it is characterized in that described spray is 50～500nm.
3. triamcinolone acetonide acetate flexible nano lipid vesicles spray according to claim 1, the component and the proportioning that it is characterized in that flexible nano lipid vesicles are as follows: the percentage by weight of triamcinolone acetonide acetate is 0.1%, the percentage by weight of phospholipid is 4%, and the percentage by weight of sodium cholate is 0.77%.
4. according to the preparation method of spray described in claim 1 and claim 3, step is as follows.
(1) by phospholipid, triamcinolone acetonide acetate in eggplant-shape bottle, add chloroform-methanol (1: 1, v/v) mixed solvent 30ml, in 37 DEG C of waters bath with thermostatic control, water pump evaporation under reduced pressure removed organic solvent, forms the even lipoids thin film of one deck, nitrogen injection at bottle inwall;
(2) in the lipoids thin film of preparing, add the aqueous solution of softening agents, film 2h is washed in rotation;
(3) above-mentioned aqueous solution probe-type under ice-water bath condition of preparing gained is interrupted to ultrasonic 15min, 0.22 μ m filtering with microporous membrane, prepare uniform flexible nano lipid vesicles, be mixed and made into triamcinolone acetonide acetate flexible nano lipid vesicles spray with certain proportioning distilled water.
5. method according to claim 4, is characterized in that triamcinolone acetonide acetate flexible nano lipid vesicles that described method also comprises prepared by described step (3) is through steam sterilization, filtration, the aseptic subpackaged step to aerosol container.
6. triamcinolone acetonide acetate flexible nano lipid vesicles spray according to claim 3, the mean diameter that it is characterized in that described spray is 100～200nm, its 12h accumulation transit dose in vitro hypertrophic cicatrix skin is respectively common nanometer liposome and commercially available emulsifiable paste 2.20 and 4.43 times, and the hold-up of administration 12h targeting hypertrophic cicatrix epidermis and corium is respectively 5.44 and 7.72 times of commercially available emulsifiable paste.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074387A (en) * | 2016-08-15 | 2016-11-09 | 辽宁大学 | There is thixotropic triamcinolone acetonide nasal spray and preparation method thereof |
| CN108430457A (en) * | 2015-12-17 | 2018-08-21 | 南洋理工大学 | The nano liposomes and preparation method thereof comprising corticosteroid as drug |
| CN109481403A (en) * | 2018-12-04 | 2019-03-19 | 山东大学齐鲁医院 | A kind of chitosan-modified triamcinolone acetonide acetate liposome and preparation method |
| CN114831939A (en) * | 2021-01-30 | 2022-08-02 | 南京星银药业集团有限公司 | Triamcinolone acetonide acetate composition spray and preparation method thereof |
| CN117357480A (en) * | 2023-12-08 | 2024-01-09 | 北京中科利华医药研究院有限公司 | Composition for needleless percutaneous injection |
-
2013
- 2013-05-23 CN CN201310198757.1A patent/CN104173285A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108430457A (en) * | 2015-12-17 | 2018-08-21 | 南洋理工大学 | The nano liposomes and preparation method thereof comprising corticosteroid as drug |
| CN106074387A (en) * | 2016-08-15 | 2016-11-09 | 辽宁大学 | There is thixotropic triamcinolone acetonide nasal spray and preparation method thereof |
| CN106074387B (en) * | 2016-08-15 | 2019-09-13 | 辽宁大学 | With thixotropic Triamcinolone acetonide nasal spray and preparation method thereof |
| CN109481403A (en) * | 2018-12-04 | 2019-03-19 | 山东大学齐鲁医院 | A kind of chitosan-modified triamcinolone acetonide acetate liposome and preparation method |
| CN109481403B (en) * | 2018-12-04 | 2020-10-20 | 山东大学齐鲁医院 | Chitosan-modified triamcinolone acetonide acetate liposome and preparation method thereof |
| CN114831939A (en) * | 2021-01-30 | 2022-08-02 | 南京星银药业集团有限公司 | Triamcinolone acetonide acetate composition spray and preparation method thereof |
| CN117357480A (en) * | 2023-12-08 | 2024-01-09 | 北京中科利华医药研究院有限公司 | Composition for needleless percutaneous injection |
| CN117357480B (en) * | 2023-12-08 | 2024-03-29 | 北京中科利华医药研究院有限公司 | Composition for needleless percutaneous injection |
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