CN105727301A - Tretinoin/TA-beta-CD clathrate, cream containing tretinoin/TA-beta-CD clathrate, and preparation methods of tretinoin/TA-beta-CD clathrate and cream - Google Patents
Tretinoin/TA-beta-CD clathrate, cream containing tretinoin/TA-beta-CD clathrate, and preparation methods of tretinoin/TA-beta-CD clathrate and cream Download PDFInfo
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Abstract
The invention belongs to the field of pharmaceutical preparation research of pharmaceutical engineering, and particularly relates to a tretinoin/TA-beta-CD clathrate and preparation of cream containing the tretinoin/TA-beta-CD clathrate. The prepared tretinoin/TA-beta-CD clathrate can improve photostability and thermostability of tretinoin. The cream containing the tretinoin/TA-beta-CD clathrate has characteristics of improved transdermal permeability, slow-released medical molecules, and lasting action time, and can reduce irritation and toxic and side functions of tretinoin. Besides the cream, the tretinoin/TA-beta-CD clathrate can further be widely applied to research of various preparation forms. The preparation methods adopted in the invention are mature, simple, and convenient, are suitable for massive production, and can bring considerable economic benefit.
Description
Technical field
The invention belongs to the pharmaceutical preparation research field of pharmaceutical engineering, be specifically related to a kind of retinoic acid/TA-beta-CD inclusion and the preparation containing retinoic acid/TA-beta-CD inclusion ointment, its range of application relates to the fields such as clinical medicine preparation and beautifying medical.
Background technology
Retinoic acid (Tretinoin) has the effect of anti-keratinization, antiinflammatory, anti-sebum, is one of the choice drug of recent domestic treatment acne.But the structure of retinoic acid is have the organic monoacid of conjugated double bond, oxidizable, chance light and in atmosphere extremely unstable, so when being made into external preparation, its curative effect can be reduced, and when using, skin is caused certain zest, therefore, strengthening the stability of retinoic acid, reduce discomfort, improving its bioavailability is retinoic acid matter of utmost importance urgently to be resolved hurrily in clinical practice.
At present, a lot of new approaches and new method are provided at the Problems Existing that the new agent technology that pharmaceutical field is conventional is solution retinoic acid.Beta-schardinger dextrin-(β-Cyclodextrin, it is called for short β-CD) it is by one group of oligosaccharide of 7 D-glucopyranose units annular arrangements, as cyclic oligomer, the hydrophobic annular cavity all kinds of object of energy inclusion of beta-schardinger dextrin-, Host-guest inclusion complex is formed by intermolecular Physical interaction, the physicochemical property of object can be effectively improved, as improved dissolubility, enhanced stability and improving bioavailability etc. after forming clathrate.
The research in past was once reported retinoic acid was made beta-CD inclusion, to some extent solve retinoic acid stability problem, but, when it can be used as ointment to be administered, Transdermal absorption needs substrate to have certain lipotropy, but in the research in past, bag load β-CD used by retinoic acid is hydrophilic so that the absorption of retinoic acid is not significantly improved, and therefore Transdermal absorption effect is poor.
Summary of the invention
Technical problem solved by the invention is to provide a kind of retinoic acid/TA-beta-CD inclusion and the ointment containing retinoic acid/TA-beta-CD inclusion, its stability that can be effectively improved retinoic acid and dissolubility, and, lipophilic retinoic acid/TA-beta-CD inclusion can improve retinoic acid transdermal permeability slow releasing drug molecule, and action time is lasting.
The present invention also provides for that a kind of method is simple and easy, the retinoic acid/TA-beta-CD inclusion of technical maturity and the technology of preparing containing retinoic acid/TA-beta-CD inclusion ointment.
For achieving the above object, the present invention is achieved through the following technical solutions:
The preparation of retinoic acid/TA-beta-CD inclusion
The present invention prepares retinoic acid/TA-beta-CD inclusion by following technical proposals, and described retinoic acid/TA-beta-CD inclusion is made up of by thing mass ratio following raw material, retinoic acid: TA-β-CD is 1:0.5～5, adopts sealing schedule temperature control technique to prepare.
Above-mentioned lipotropy TA-β-CD refers to: (1) acyl group beta-cyclodextrin derivative, including 2,3,6 triacetyl beta-schardinger dextrin-s, 2,3,6 three propiono beta-schardinger dextrin-s, 2,3,6 three bytyry beta-schardinger dextrin-s, 2,3,6 three acyl group beta-schardinger dextrin-s；(2) Ethylated β-Cyclodextrins derivant, including 2,6 diethyl beta-schardinger dextrin-s, 2,3,6 triethyl group beta-schardinger dextrin-s.
Concrete preparation method is: by retinoic acid: TA-β-CD amount of substance is than 1:0.5～5, weigh TA-β-CD and retinoic acid is appropriate, physical mixture is made with vortex mixer mixing 1min, physical mixture is sub-packed in sealing by fusing in 2mL ampoule, it is placed in temp controlling heater, 70 DEG C-80 DEG C sealing schedule temperature control heating 1～3h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
In above-mentioned preparation method, selecting amount of substance than 1:1, temperature control 75 DEG C, heating 2h is best.
Productivity and entrapment efficiency determination
Weigh the retinoic acid/TA-beta-CD inclusion prepared by " embodiment 1～4 " and retinoic acid/beta-CD inclusion (comparative example respectively, TA-β-CD in " embodiment 1～4 " is changed to β-CD) appropriate, the clathrate productivity recorded according to " embodiment 5 " and envelop rate, result is as shown in table 1.
The productivity of table 1. clathrate and envelop rate
It is shown that under any proportioning, productivity and the envelop rate of retinoic acid/TA-beta-CD inclusion are above retinoic acid/beta-CD inclusion；Additionally, compare β-cdinclusion, with TA-β-cdinclusion retinoic acid, just can obtain maximum yield and envelop rate when proportioning reaches 1:1 and 1:3, illustrate that the affinity between lipotropy TA-β-CD and insoluble drug retinoic acid is significantly better than hydrophilic β-CD.
The sign of retinoic acid/TA-beta-CD inclusion
The present invention is respectively adopted " embodiment 6 " and the method for " embodiment 7 ", retinoic acid, TA-β-CD, retinoic acid and TA-β-CD mixture and retinoic acid/TA-beta-CD inclusion (" embodiment 2 ") are tested through powder x-ray diffraction and DSC respectively, and result is shown in Fig. 1 and Fig. 2.As seen from Figure 1, the characteristic diffraction peak of retinoic acid self is 14.7 °, 16.9 °, 22.3 °；The characteristic diffraction peak of TA-β-CD self is 6.5 °, 10.7 °, 19.27 °；Retinoic acid and physical mixture collection of illustrative plates in, still can retinoic acid visible in detail and the TA-original characteristic diffraction peak of β-CD in above-mentioned position；And there is not the characteristic diffraction peak of retinoic acid and TA-β-CD in existing together in clathrate, the interaction showing retinoic acid and TA-β-CD is not simple physical mixed, but the original crystalline structure of retinoic acid is changed, enter in TA-β-CD void structure with molecularity and define a kind of new thing phase, cause that crystal formation changes and make its original characteristic peak disappear.From Figure 2 it can be seen that in the DSC curve of retinoic acid about 175.02 DEG C endothermic peak occurs, for its melted endothermic peak；In the DSC curve of TA-β-CD, about 185.56 DEG C there is endothermic peak, for its melted endothermic peak；In the retinoic acid physical mixture DSC curve with TA-β-CD, the melted endothermic peak of retinoic acid and TA-β-CD still being can be observed at 172.21 DEG C and 183.22 DEG C places, owing to mixing makes its fusing point slightly decline, peak area reduces simultaneously；And retinoic acid and the melted endothermic peak of TA-β-CD are wholly absent in clathrate, DSC test further demonstrates and defines molecular clathrate between retinoic acid and TA-β-CD.
Light durability experimental result
Take retinoic acid/TA-beta-CD inclusion (" embodiment 1～4 ") and the retinoic acid/beta-CD inclusion (comparative example of each proportioning, TA-β-CD in " embodiment 1～4 " is changed to β-CD) each 50mg, it is respectively placed in water white glass container, stand cloth thickness≤5mm, it is placed under 4500lx ± 500lx illumination and carries out photolysis experiments, timing sampling measures retinoic acid content, and result is as shown in table 2.
Table 2. light durability experimental result
Result shows under different ratio, and the light durability of retinoic acid/TA-beta-CD inclusion is all significantly better than retinoic acid/beta-CD inclusion.
Heat setting experimental result
Take retinoic acid/TA-beta-CD inclusion (" embodiment 1～4 ") and the retinoic acid/beta-CD inclusion (comparative example of each proportioning, TA-β-CD in " embodiment 1～4 " is changed to β-CD) each 50mg, it is respectively placed in water white glass container, stand cloth thickness≤5mm, it is placed in the thermostatic drying chamber of 60 DEG C, timing sampling measures retinoic acid content, and result is as shown in table 3.
Table 3. heat stability experimental result
Result shows under different ratio, and the heat stability of retinoic acid/TA-beta-CD inclusion is significantly better than retinoic acid/beta-CD inclusion.
Vitro drug release experimental result
Tretinoin cream, as dermatologic, will produce therapeutical effect, and first, its medicine must be discharged into skin or mucomembranous surface from emulsifiable paste matrix, and therefore, the medicine releasability of emulsifiable paste is also one of important indicator of emulsifiable paste quality evaluation.The present invention tests by " embodiment 11 " prepare containing retinoic acid/TA-β-CD ointment (experimental example) and containing retinoic acid/beta-CD inclusion (comparative example, take retinoic acid/β-CD100g, other are with " embodiments 11 ") vitro drug release, result is as shown in Figure 3, being shown by release profiles, the cumulative maximum burst size of retinoic acid/TA-β-CD is 88.1%；And the cumulative maximum burst size of retinoic acid/β-CD is only 71.0%, the retinoic acid lipophilic TA-β-CD being thus described and have long aliphatic chain interacts than hydrophilic-β-CD more more preferably, can be effectively improved the dissolubility of insoluble drug through inclusion, enhanced stability is avoided being destroyed in release process；Simultaneously it can also be observed that the maximum disengagement time that reaches of retinoic acid/TA-β-CD is slightly longer than retinoic acid/β-CD, illustrate that the release of retinoic acid is served the effect of slow release by TA-β-CD.
Transdermal absorption experimental result
The method adopting " embodiment 13 ", will containing retinoic acid/TA-β-CD ointment (experimental example, prepare by embodiment 11), containing retinoic acid/β-CD ointment (comparative example, take retinoic acid/β-CD100g, other are with " embodiment 11 ") by transdermal test, result is shown in Fig. 4, shown by Transdermal absorption curve, at each time point, the transdermal penetration rate of the embodiment of the present invention is all apparently higher than the transdermal penetration rate of comparative example, illustrate that the retinoic acid through lipotropy TA-β-cdinclusion is better to skin moisturizing and spreadability, can effectively pass through epidermal tissue, improve Transdermal absorption effect.
The screening of cutaneous permeable agent kind
The Transdermal absorption of medicine is affected particularly important by the kind of cutaneous permeable agent, the present invention adopts the method for " embodiment 13 ", having investigated azone, menthol and Borneolum Syntheticum (consumption participation in the election " embodiment 11 ") respectively as the cutaneous permeable agent impact on the Transdermal absorption of retinoic acid, result is in Table 4.
The promotion to the Transdermal absorption of retinoic acid of the table 4. cutaneous permeable agent kind
It is shown that when not adding Percutaneous absorption enhancer, it is better than retinoic acid/beta-CD inclusion through the Transdermal absorption effect of the retinoic acid/TA-beta-CD inclusion of lipotropy TA-β-cdinclusion, illustrates that TA-β-CD is conducive to the Transdermal absorption of retinoic acid；After adding Percutaneous absorption enhancer, the Transdermal absorption facilitation of Borneolum Syntheticum and menthol is significantly better than azone, its reason is retinoic acid is fat-soluble medicine, and the effect of hydrophilic medicament is better than lipophilic drugs by azone, so selecting Borneolum Syntheticum or menthol as the Percutaneous absorption enhancer of retinoic acid in the present invention, additionally, due to Borneolum Syntheticum has the effect of erosion prevention and muscle growing, anti-inflammation and sterilization, it is preferred, therefore, that use Borneolum Syntheticum.
In sum, first retinoic acid is made clathrate with lipotropy TA-β-CD by sealing schedule temperature control technique by the present invention, and the inclusion productivity of lipotropy TA-β-CD, envelop rate and stability are significantly better than β-CD；The illumination of retinoic acid/TA-beta-CD inclusion and heat stability are significantly better than retinoic acid/beta-CD inclusion；Transdermal absorption containing retinoic acid/TA-beta-CD inclusion ointment is substantially better than containing retinoic acid/beta-CD inclusion, and bioavailability is significantly improved；The present invention have selected different Percutaneous absorption enhancers, it is shown that with Borneolum Syntheticum or menthol as Percutaneous absorption enhancer, its effect is significantly better than azone.
Retinoic acid prepared by the present invention/TA-beta-CD inclusion is owing to having better lipotropy, therefore, has good Transdermal absorption effect, can be used for external preparation, such as emulsifiable paste, patch etc., thus improving the Transdermal absorption of medicine.
The method have the benefit that:
1, the present invention adopts the TA-β-cdinclusion retinoic acid of lipotropy and good biocompatibility, and technique used is simple, strong operability.2, the productivity of retinoic acid/TA-beta-CD inclusion and envelop rate are above retinoic acid/beta-CD inclusion, illustrate that the affinity between fat-soluble retinoic acid and lipotropy TA-β-CD is significantly better than hydrophilic β-CD.
3, our experiments show that, retinoic acid/TA-beta-CD inclusion is compared with retinoic acid/beta-CD inclusion, heat and light durability significantly improve, illustrate that lipophilic TA-β-CD mates with the retinoic acid character with long aliphatic chain, it is more readily formed stable clathrate, its dissolubility can be improved, strengthen its stability.
4, the present invention selects Borneolum Syntheticum or menthol as the Percutaneous absorption enhancer of retinoic acid, and effect is significantly better than azone, owing to Borneolum Syntheticum has the effect of erosion prevention and muscle growing, anti-inflammation and sterilization, so, present invention preferably uses Borneolum Syntheticum.
5, by showing with extracorporeal releasing experiment containing retinoic acid/β-CD ointment (comparative example) containing retinoic acid/TA-β-CD ointment (experimental example), the preparation of experimental example is apparently higher than comparative example.
6, by containing retinoic acid/TA-β-CD ointment (experimental example) with containing retinoic acid/β-CD ointment (comparative example) Transdermal absorption experiments show that, the transdermal absorption factor of experimental example is apparently higher than comparative example, used by the present invention, TA-β-CD is lipotropy, itself there is very strong percutaneous absorbability, be conducive to the transdermal penetration of ointment, the bioavailability of medicine can be improved.
Accompanying drawing illustrates:
Fig. 1 is X-ray diffracting spectrum；
A-retinoic acid；b-TA-β-CD；C-retinoic acid and TA-β-CD mixture；D-retinoic acid and TA-beta-CD inclusion；
Fig. 2 is that DSC detects collection of illustrative plates；
A-retinoic acid；b-TA-β-CD；C-retinoic acid and TA-β-CD mixture；D-retinoic acid and TA-beta-CD inclusion；
Fig. 3 is release in vitro comparison diagram；
Fig. 4 is transdermal penetration comparison diagram.
Detailed description of the invention
The preparation of embodiment 1 retinoic acid/TA-beta-CD inclusion
TA-β-CD and retinoic acid 100g is weighed than 1:0.5 by amount of substance, physical mixture is made with vortex mixer mixing 1min, physical mixture is sub-packed in sealing by fusing in 2mL ampoule, it is placed in temp controlling heater, 75 DEG C of sealing schedule temperature control heating 2h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
The preparation of embodiment 2 retinoic acid/TA-beta-CD inclusion
TA-β-CD and retinoic acid 100g is weighed than 1:1 by amount of substance, mixture is made with vortex mixer mixing 1min, physical mixture is sub-packed in sealing by fusing in 2mL ampoule, it is placed in temp controlling heater, after 75 DEG C of sealing schedule temperature control heating 2h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
The preparation of embodiment 3 retinoic acid/TA-beta-CD inclusion
TA-β-CD and retinoic acid 100g is weighed than 1:3 by amount of substance, physical mixture is made with vortex mixer mixing 1min, physical mixture is sub-packed in sealing by fusing in 2mL ampoule, it is placed in temp controlling heater, 75 DEG C of sealing schedule temperature control heating 2h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
The preparation of embodiment 4 retinoic acid/TA-beta-CD inclusion
By retinoic acid: TA-β-CD amount of substance compares 1:5, weigh TA-β-CD and retinoic acid is appropriate, physical mixture is made with vortex mixer mixing 1min, physical mixture is sub-packed in sealing by fusing in 2mL ampoule, it is placed in temp controlling heater, 75 DEG C of sealing schedule temperature control heating 2h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
Embodiment 5 clathrate productivity and envelop rate test
Take retinoic acid/TA-beta-CD inclusion " embodiment 1～4 " and the retinoic acid/beta-CD inclusion (comparative example of each proportioning, TA-β-CD in " embodiment 1～4 " is changed to β-CD) appropriate, dissolve with 50mL isopropanol, it is settled to scale, therefrom draw 1mL to measure at 352nm place, under this wavelength, TA-β-CD and β-CD is noiseless, substitute into standard curve c=8.325A+0.2637 (R=0.9999), calculate retinoic acid concentration and obtain its content, being calculated as follows the rate of output and envelop rate.
Embodiment 6 powder x-ray diffraction measures
Take retinoic acid, TA-β-CD, retinoic acid and TA-β-CD mixture and retinoic acid and TA-beta-CD inclusion (preparing by " embodiment 2 "), D/max-AX-x ray diffractometer x is adopted to measure, condition determination: room temperature, Cu-Ka radiates, 30kV, tube current 100mA, 5 ° of min of scanning speed-1, measurement range 2 θ is 5～35 °.
Embodiment 7 differential scanning is tested
Take retinoic acid, TA-β-CD, retinoic acid and TA-β-CD mixture and retinoic acid and TA-beta-CD inclusion (preparing by " embodiment 2 "), DSC-60DifferentialScanningCalorimeter is adopted to measure, 20 DEG C～350 DEG C temperature ranges, with 5 DEG C of min-1Ramp, N2DSC curve is drawn under protection.
Embodiment 8 illumination qualitative experiment
Weigh the retinoic acid/TA-beta-CD inclusion prepared by " embodiment 1～4 " and retinoic acid/beta-CD inclusion (comparative example respectively, TA-β-CD in " embodiment 1～4 " is changed to β-CD) each 50mg, it is respectively placed in water white glass container, stand cloth thickness≤5mm, it is placed under 4500lx ± 500lx illumination and carries out photolysis experiments, respectively at 6,12,24h sampling, calculate retinoic acid content by " embodiment 5 " standard curve.
Embodiment 9 heat setting is tested
Weigh the retinoic acid/TA-beta-CD inclusion prepared by " embodiment 1～4 " and retinoic acid/beta-CD inclusion (comparative example respectively, TA-β-CD in " embodiment 1～4 " is changed to β-CD) each 50mg, it is respectively placed in water white glass container, stand cloth thickness≤5mm, it is placed in the thermostatic drying chamber of 60 DEG C, respectively at 6,12,24h sampling, calculate retinoic acid content by " embodiment 5 " standard curve.
The preparation method of embodiment 10 emulsifiable paste matrix
Matrix formulations: glyceryl monostearate 8 one 12 weight portion, white vaseline 8 one 12 weight portion, stearic acid 10 1 15 weight portion, sodium lauryl sulphate 0.5 1 2.0 weight portion, glycerol 8 one 12 weight portion, Borneolum Syntheticum 1 one 5 weight portion, ethylparaben 0.5 1 1.0 weight portion, distilled water 80 1 120 weight portion.
Concrete enforcement is: take glyceryl monostearate 100g, white vaseline 100g, stearic acid 120g, Borneolum Syntheticum 3g put in container, and heating is molten into oil phase, and keeping temperature is 80 DEG C；Separately take sodium lauryl sulphate 10g, glycerol 100g, distilled water 1000g put in another container as aqueous phase, and heating, to 80 DEG C, adds nipagin A 5g, it is dissolved in after aqueous phase until it, slowly aqueous phase is added in oil phase, stir at same direction, until white fine and smooth paste.
Embodiment 11 is containing the preparation of retinoic acid/TA-beta-CD inclusion ointment
The ointment of retinoic acid of the present invention/TA-beta-CD inclusion is made up of the raw material of following weight proportioning: retinoic acid/TA-beta-CD inclusion (embodiment 2) 8 one 12 weight portions, glyceryl monostearate 8 one 12 weight portion, white vaseline 8 one 12 weight portion, stearic acid 10 1 15 weight portion, sodium lauryl sulphate 0.5 1 2.0 weight portion, glycerol 8 one 12 weight portion, Borneolum Syntheticum (or azone, Borneolum Syntheticum, quintessence oil class, Organic Alcohol etc.) 1 one 5 weight portions, ethylparaben 0.5 1 1.0 weight portion, distilled water 80 1 120 weight portion.
The weight proportion of best each raw material is:
Retinoic acid/TA-beta-CD inclusion (embodiment 2) 10 weight portions, glyceryl monostearate 10 weight portion, white vaseline 10 weight portion, stearic acid 12 weight portion, sodium lauryl sulphate 1.0 weight portion, glycerol 10 weight portion, Borneolum Syntheticum (or Mentholum) 3 weight portion, ethylparaben 0.5 weight portion, distilled water 100 weight portion.
Concrete enforcement is: add in the emulsifiable paste matrix that " embodiment 10 " prepares by the retinoic acid/TA-beta-CD inclusion 100g of preparation in above-mentioned " embodiment 2 " by equal increments method, after mix homogeneously, seal subpackage, obtain milky, uniform and smooth, the ointment containing retinoic acid/TA-beta-CD inclusion that denseness is suitable.
Embodiment 12 vitro drug release is tested
Taking the microporous filter membrane of 1pm, be fixed between the supply pool of diffusion cell and acceptance pool, circulating water temperature is maintained at 37 DEG C ± 0.5 DEG C, and acceptance pool is with the phosphate buffer of pH7.4 for accepting medium, with 100r min-1Speed stirring, then, be separately added into containing retinoic acid/TA-β-CD ointment (embodiment 11) and containing retinoic acid/β-CD ointment (comparative example in supply chamber, taking retinoic acid/β-CD100g, other are with " embodiment 11 "), 0.5,1,2,3,4,5, when 6,12h separately sampled, after sampling supplement equal-volume equitemperature blank release medium.Release liquid, with 0.45 μm of filtering with microporous membrane, discards just filtrate, and subsequent filtrate adopts determined by ultraviolet spectrophotometry.
Embodiment 13 Transdermal absorption is tested
Mouse skin is fixed on the upper of Franz diffusion cell by Transdermal absorption experiment, between lower room, horny layer is upward, respectively with containing retinoic acid/TA-β-CD ointment (embodiment 11), containing retinoic acid/β-CD ointment (comparative example, take retinoic acid/β-CD100g, other are with " embodiment 11 ") close contact, the phosphate buffer of pH7.4 is contained in acceptance pool, acceptable solution is just contacted with dermal layer of the skin, constant speed stirring is kept at constant temperature (37 ± 1) DEG C, in 0.5, 1, 2, 3, 4, 6, 12h takes out in receiving chamber and all receives liquid, add equivalent immediately, the blank acceptable solution of isothermal, through the filtering with microporous membrane of 0.45 μm, discard just filtrate, collect subsequent filtrate, measure retinoic acid content.
Claims (10)
1. retinoic acid/TA-beta-CD inclusion, it is characterised in that retinoic acid/TA-beta-CD inclusion is made up of by thing mass ratio following raw material, retinoic acid: TA-β-CD is 1:0.5～5, adopts sealing schedule temperature control technique to prepare.
2. retinoic acid/TA-beta-CD inclusion as claimed in claim 1, it is characterised in that retinoic acid: TA-β-CD is 1:1～3.
3. the preparation method of retinoic acid/TA-beta-CD inclusion as claimed in claim 1: it is characterized in that, weigh retinoic acid by amount of substance ratio and TA-β-CD is appropriate, it is mixed and made into physical mixture with vortex mixer, it is sub-packed in ampoule by physical mixture sealing by fusing, it is placed in temp controlling heater, 70 DEG C of one 80 DEG C of sealing schedule temperature controls heating 1 one 3h, place to room temperature, take out to obtain retinoic acid/TA-beta-CD inclusion.
4. preparation method as claimed in claim 3, it is characterised in that temperature control 75 DEG C.
5. preparation method as claimed in claim 3, it is characterised in that heating 2h.
6. retinoic acid/TA-beta-CD inclusion as claimed in claim 1, it is characterised in that described retinoic acid/TA-beta-CD inclusion adds Percutaneous absorption enhancer thus improving the Transdermal absorption of retinoic acid.
7. retinoic acid/TA-beta-CD inclusion as claimed in claim 6, it is characterised in that described Percutaneous absorption enhancer is selected from azone, Borneolum Syntheticum or menthol, it is preferable that Borneolum Syntheticum.
8. the ointment of retinoic acid/TA-beta-CD inclusion, it is characterized in that, retinoic acid/TA-beta-CD inclusion 5 12 weight portion, glyceryl monostearate 8 12 weight portion, white vaseline 8 12 weight portion, stearic acid 10 15 weight portion, sodium lauryl sulphate 0.5 2.0 weight portion, glycerol 8 12 weight portion, Borneolum Syntheticum 15 weight portion, ethylparaben 0.5 1.0 weight portion, distilled water 80 120 weight portion.
9. the ointment of retinoic acid/TA-beta-CD inclusion, it is characterized in that, retinoic acid/TA-beta-CD inclusion 10 weight portion, glyceryl monostearate 10 weight portion, white vaseline 10 weight portion, stearic acid 12 weight portion, sodium lauryl sulphate 1.0 weight portion, glycerol 10 weight portion, Borneolum Syntheticum 3 weight portion, ethylparaben 0.5 weight portion, distilled water 100 weight portion.
10. the preparation method of ointment as claimed in claim 8 or 9, it is characterised in that
The preparation of cream base: take glyceryl monostearate 100g, white vaseline 100g, stearic acid 120g, Borneolum Syntheticum 3g put in container, and heating is molten into oil phase, keeping temperature is 80 DEG C；Separately take sodium lauryl sulphate 10g, glycerol 100g, distilled water 1000g put in another container as aqueous phase, and heating, to 80 DEG C, adds nipagin A 5g, it is dissolved in after aqueous phase until it, slowly aqueous phase is added in oil phase, stir at same direction, until white fine and smooth paste；
Preparation containing retinoic acid/TA-β-CD emulsifiable paste: retinoic acid/TA-beta-CD inclusion 100g is pressed equal increments method and adds in emulsifiable paste matrix, after mix homogeneously, seal subpackage, obtain milky, uniform and smooth, the ointment containing retinoic acid/TA-beta-CD inclusion that denseness is suitable.
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| CN114209687A (en) * | 2021-12-20 | 2022-03-22 | 重庆华邦制药有限公司 | Composition of tretinoin external medicine |
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| CN114209687A (en) * | 2021-12-20 | 2022-03-22 | 重庆华邦制药有限公司 | Composition of tretinoin external medicine |
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Application publication date: 20160706 |