CN102871989B - New application of honokiol or pharmaceutically acceptable salt of honokiol - Google Patents
New application of honokiol or pharmaceutically acceptable salt of honokiol Download PDFInfo
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- CN102871989B CN102871989B CN201210229902.3A CN201210229902A CN102871989B CN 102871989 B CN102871989 B CN 102871989B CN 201210229902 A CN201210229902 A CN 201210229902A CN 102871989 B CN102871989 B CN 102871989B
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Abstract
The invention belongs to the field of a medicine, and relates to a new application of either he honokiol or a pharmaceutically acceptable salt of the honokiol and an external preparation containing either honokiol or the pharmaceutically acceptable salt of honokiol. The new application is specially an application of a medicine for treating excessive keratinization and keratotic skin diseases. With the adoption of the new medicinal application, external preparation is prepared by adding common adjuvants in the pharmacy into either honokiol or the pharmaceutically acceptable salt of honokiol as a main active component or an exclusive component. According to the invention, the external preparation contains the following components by weight: 0.01% to 10% of either honokiol or the pharmaceutically acceptable salt of honokiol and 0.1% to 10% of high-efficient skin penetration enhancer. The above external preparation containing either honokiol or the pharmaceutically acceptable salt of honokiol can be utilized to implement an aim of treating the keratotic skin diseases in the way of transdermal delivery, and cutaneous penetration is obvious and an effect is remarkable, so that a new selection is provided for a clinical treatment.
Description
Technical field
The invention belongs to field of medicaments, relate to the novelty teabag of honokiol or its pharmaceutically acceptable salt, and containing the external preparation of honokiol or its pharmaceutically acceptable salt, novelty teabag is specially the purposes in the medicine of the keratosa dermatosis of preparation treatment, autoimmune disease.
Background technology
Honokiol, English by name Honokiol, chemistry 3', 5-by name bis--2-acrylic-1,1'-biphenyl-2,4'-diphenol.It is that extraction and isolation one out has extensive bioactive micromolecular compound from the skin of Cortex Magnoliae Officinalis Magnolia officinalis Rehd.et Wils., and its primary bioactivity comprises antimicrobial, antioxidation, anxiety, antidepressant and antithrombotic.In recent years, new research display honokiol has very strong anti-tumor activity, and wherein one of the mechanism of antitumor action is inhibiting angiogenesis.
Inventor, through having experimental studies have found that new effect, can be used for the treatment of keratosa dermatosis, autoimmune disease, and above-mentioned two kinds of effects are not also by existing bibliographical information, belong to the new opplication of honokiol.
Summary of the invention
First technical problem solved by the invention is to provide honokiol or the novelty teabag of its pharmaceutically acceptable salt in the medicine of preparation treatment hyperkeratinization.Further, utilize this novelty teabag, honokiol or the novelty teabag of its pharmaceutically acceptable salt in the keratosa dermopathic medicine of preparation treatment are provided.
Inventor is by K14-VEGF transgenic cow tinea mouse model (purchased from American Jackson Lab, after bred by Biotherapeutics National Key Laboratory of Sichuan University, gone down to posterity and raise) represent keratosa dermatosis scale-model investigation and find, honokiol or its pharmaceutically acceptable salt can obviously alleviate model mice ear epidermis edema, promotion epidermis thinning, weaken the not congruent phenomenon of keratinization.Inventor also represents keratosa dermatosis scale-model investigation by propranolol guinea pig model and finds, honokiol or its pharmaceutically acceptable salt and positive drug all obviously can make that its hard of hearing redness of Cavia porcellus alleviates, horny layer is significantly thinning, hyperkeratinization lightens, granular layer is embarked on journey continuously distribution, spinous layer are significantly thinning than model group, basal cell trochanterellus also becomes smooth and dermal papilla to rise into shaft-like phenomenon less.The Cavia porcellus ear skin recovery effects of honokiol or the treatment of its pharmaceutically acceptable salt is better than positive drug.Applicable keratosa dermatosis be ichthyosis, getting blisters property epidermolysis bullosa disease, psoriasis, coloring xeroderma, follicular keratosis, porokeratosis of Mibelli, keratosis palmaris et plantaris, Progressive symmetric erythrokeratodermia symmetry erythema cuticle disease, menopause cuticle disease, exfoliative cutin absent-mindedness disease, avitaminosis, any one in scleroderma.
Second technical problem solved by the invention is to provide honokiol or its pharmaceutically acceptable salt is preparing the novelty teabag had in the medicine of immunosuppressive action.
Inventor represents Autoimmune Disease Models research by K14-VEGF transgenic cow tinea mouse model equally and finds, honokiol or its pharmaceutically acceptable salt can reduce IFN-γ in animal serum, TNF-α secretion level, and on IL-2, IL-4 and IL-10 almost without impact.Study IFN-γ, TNF-α gene expression dose in mouse ear tissue further, result also shows the mrna expression level that honokiol or its pharmaceutically acceptable salt can suppress IFN-γ, TNF-α.By lowering CD3 in lymphocyte to honokiol or its pharmaceutically acceptable salt immunosuppressant target cell result of study display honokiol or its pharmaceutically acceptable salt
+t cell, CD4
+the expression of T cell, the expression of lowering Th1 cell further plays immunosuppressive action, is particularly useful for treating psoriasis.
And have in the process of pharmacological action find at research honokiol or its pharmaceutically acceptable salt, be main active or sole active agent with honokiol, when making external preparation, the object for the treatment of keratosa dermatosis and autoimmune disease can be realized.
3rd technical problem solved by the invention is: the new pharmaceutical usage utilizing honokiol or its pharmaceutically acceptable salt, to make with honokiol or its pharmaceutically acceptable salt as main active or sole active agent, add pharmaceutics and commonly use the external preparation that adjuvant makes.
In external preparation of the present invention, the component containing following weight percentage ratio:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%.
Wherein, described highly effective skin penetration enhancer is one in water-solubleazone, propylene glycol, Mentholum or its mixture.
In external preparation of the present invention, also containing percentage by weight is 0.001%-0.05% antiseptic, that is:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%
Antiseptic 0.001%-0.05%.
Honokiol pharmaceutically acceptable salt can adopt honokiol disodium salt, honokiol di-potassium etc.
Adjuvant that external preparation is commonly used, conventional amount used also can be added in external preparation.Make as external preparation such as emulsifiable paste, varnish, liniment, lotions.
Utilize the external preparation of above-mentioned honokiol or its pharmaceutically acceptable salt can realize treating with the approach of transdermal administration the object of keratosa dermatosis and autoimmune disease, and transdermal effect is obvious, treatment ichthyosis, getting blisters property epidermolysis bullosa disease, psoriasis, coloring xeroderma, follicular keratosis, porokeratosis of Mibelli, keratosis palmaris et plantaris, Progressive symmetric erythrokeratodermia symmetry erythema cuticle disease, menopause cuticle disease, exfoliative cutin absent-mindedness disease, avitaminosis, sclerodermatous Be very effective, for clinical treatment provides a kind of selection completely newly.
Accompanying drawing explanation
Fig. 1 treats K14-VEGE transgenic mice ear imaging after 4 weeks
Fig. 2 treats mouse ear (H & E, × 200) after 2 weeks
Fig. 3 treats mouse ear (H & E, × 200) after 4 weeks
Fig. 4 treats mouse ear (H & E, × 200) after 6 weeks
Fig. 5 treats Cavia porcellus ear dyeing (H & E, × 200) after 12 days
Fig. 6 serum I FN-γ level (*, p < 0.05vs model; *, p < 0.01vs model)
Fig. 7 serum TNF-cc level (*, p < 0.05vs model; *, p < 0.01vs model)
Fig. 8 serum IL-2 level (*, p < 0.05vs model; *, p < 0.01vs model)
Fig. 9 levels of IL-4 (*, p < 0.05vs model; *, p < 0.01vs model)
Figure 10 RT-PCR detects the expression of K14-VEGF transgenic mice ear IFN-γ and TNF-α mRNA
Figure 11 treats the expression (× 200) of E-selectin (selecting element-E) in mouse ear after 4 weeks
Figure 12 treats the expression (× 200) of ICAM-1 in mouse ear after 4 weeks
Figure 13 treats the expression (× 200) of VCAM-1 in mouse ear after 4 weeks
Figure 14 treats the expression (× 200) of VEGFR-2 in mouse ear after 4 weeks
Figure 15 treats the phosphorylation level (× 200) of VEGFR-2 in mouse ear after 4 weeks
Figure 16 treats the phosphorylation level (× 200) of AKT in mouse ear after 4 weeks
Figure 17 treats the phosphorylation level (× 200) of ERK1/2 in mouse ear after 4 weeks
Figure 18 treats the phosphorylation level (× 200) of p38 in mouse ear after 4 weeks
Wherein, FVB/N representative is normal rat group.
Detailed description of the invention
Illustrate below by way of specific description of embodiments of the present invention but do not limit the present invention.
In order to utilize novelty teabag of the present invention, i.e. honokiol or its pharmaceutically acceptable salt purposes in the medicine of the preparation keratosa dermatosis for the treatment of and autoimmune disease, with honokiol or its pharmaceutically acceptable salt for active component makes external preparation.The key of this external preparation be by magnolol or its pharmaceutically acceptable salt and highly effective skin penetration enhancer with the use of, reach the object of rapid osmotic, absorption, performance drug effect.
Component containing following weight percentage ratio in external preparation of the present invention:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%.
Wherein, highly effective skin penetration enhancer is one in water-solubleazone, propylene glycol, Mentholum or its mixture.
The antiseptic that percentage by weight is 0.001-0.05% can also be added in above-mentioned external preparation.Adjuvant that also commonly use containing external preparation in external preparation, conventional amount used, common dosage form has the external preparation such as emulsifiable paste, varnish, liniment, lotion.
In " honokiol or its pharmaceutically acceptable salt ", " pharmaceutically acceptable salt " also can be called " pharmaceutical salts ".
And from use convenience, storage convenience, inventor determine using emulsifiable paste as exemplary dosage form, realize the object of honokiol or the keratosa dermatosis of its pharmaceutically acceptable salt external curing and autoimmune disease.
Prescription and the preparation method of emulsifiable paste of the present invention are as follows:
Prescription
Described highly effective skin penetration enhancer is selected from water-solubleazone, propylene glycol, Mentholum etc., or their mixture; Described antiseptic is selected from propyl p-hydroxybenzoate etc.
Method for making
Take oil phase substrate glyceryl monostearate, stearic acid, white vaseline, liquid paraffin by prescription precision, be placed in dry beaker altogether, heating in water bath to 90 DEG C, make its fine melt and stir and obtain oil phase; Accurately measure G & W by prescription again and be placed in another dry beaker altogether, heating in water bath to 85 DEG C, then add SDS, highly effective skin penetration enhancer and antiseptic, make it entirely molten and stir and obtain aqueous phase; Oil phase is slowly added aqueous phase, and limit edged stirs, until cooling, and Virgin's milk dosage form substrate of namely having leisure; Honokiol is ground into fine powder, takes appropriate, be dissolved in (concentration guaranteeing finally to add dimethyl sulfoxide in substrate is 0.1%) in a small amount of dimethyl sulfoxide, be then added in blank emulsion substrate, stir evenly and obtain honokiol emulsifiable paste.
Inventor is found by test, and the granularity of honokiol emulsifiable paste does not detect the particle being greater than 50 μm, meets the requirement that emulsifiable paste that Chinese Pharmacopoeia specifies must not detect the particle being greater than 180 μm.Its assay does not exceed 90% ~ 110% of labelled amount.
Study on the stability be presented at place 6 weeks denseness under 4 DEG C of-8 DEG C of conditions and sophistication all moderate, granularity does not find the particle being greater than 50 μm yet, and its content maintains the 90%-110% of labelled amount.Study on the stability be also shown in place 6 weeks denseness under the condition of 30 DEG C ± 2 DEG C and sophistication all moderate, granularity does not find the particle being greater than 50 μm yet, and its content maintains the 90%-110% of labelled amount.
Permeation test in vitro result shows honokiol emulsifiable paste at front 6h with faster rate transdermal, and percutaneous rate slows down afterwards, may be due to through honokiol in acceptable solution, be in a kind of saturation.This result also implies that honokiol suitably can enter blood through skin and play systemic circulation effect in addition, and the residue major part long period is stranded in skin outer layer or epidermal area and skin corium and plays local therapeutic effects.The transdermal absorption factor of this honokiol emulsifiable paste honokiol in 12h arrives 20% ~ 30%, and the free honokiol directly adopting 0.5% Tween 80 to dissolve under the same conditions in 12h the transdermal absorption factor of honokiol less than 10%, this shows the skin transdermal absorption factor that honokiol emulsifiable paste of the present invention improves honokiol, is conducive to medicine and plays better therapeutical effect.
The preparation of embodiment 1 honokiol emulsifiable paste
Prescription forms: by weight percentage, glyceryl monostearate (7%), stearic acid (10%), white vaseline (13%), liquid paraffin (12%), glycerol (14%), SDS (1%), water-solubleazone (1%), propyl p-hydroxybenzoate (0.02%), high dose honokiol emulsifiable paste (1%), middle dosage honokiol emulsifiable paste (0.5%), low dosage honokiol emulsifiable paste (0.1%), water (surplus).
Preparation process: take glyceryl monostearate, stearic acid, white vaseline, liquid paraffin by prescription precision and be placed in dry beaker altogether, heating in water bath to 90 DEG C, makes its fine melt and stirs and obtain oil phase; Accurately measure G & W by prescription again and be placed in another dry beaker altogether, heating in water bath to 85 DEG C, then add SDS, water-solubleazone and propyl p-hydroxybenzoate, make it entirely molten and stir and obtain aqueous phase; Oil phase is slowly added aqueous phase, and limit edged stirs, until cooling, and Virgin's milk dosage form substrate of namely having leisure; Honokiol is ground into fine powder, take appropriate, be dissolved in (concentration guaranteeing finally to add dimethyl sulfoxide in substrate is 0.1%) in a small amount of dimethyl sulfoxide, then be added in blank emulsion substrate, stir evenly and obtain 0.1% honokiol emulsifiable paste, 0.5% honokiol emulsifiable paste and 1% honokiol emulsifiable paste.
The permeation test in vitro of embodiment 2 honokiol emulsifiable paste
The preparation of rat skin in vitro: healthy SD rat is put to death, with 6% sodium sulfide, rat abdomen hair is sloughed, 3 times are repeatedly rinsed with warm saline, gauze blots, cut skin of abdomen, carefully peel off fatty tissue, choose intact skin, clean with normal saline flushing, be soaked in 4 DEG C of Refrigerator stores in normal saline and spend the night for subsequent use.
Transdermal absorption experiment and measuring: adopt skin permeation test in vitro instrument, places the junction surface of diffusion cell (keratodermatitis upward, towards supply pool by vitro Corium Mus for subsequent use; Dermal layer of the skin down, towards acceptance pool), uniform application is containing the honokiol emulsifiable paste of honokiol 25 μ g, iron clamp clamps two ponds, good seal, adds the pH7.4PBS (containing 0.5% Tween 80) of 5mL to acceptable solution to acceptance pool, ensure that liquid level has just contacted and bubble-free with skin, open magnetic agitation, revolution is 600r/min, 37 DEG C of water-bath circulations.After application of sample respectively at 0,0.5,1,2,4,6,8,10,12 and 24h from acceptance pool sampling 0.2mL acceptable solution make up equivalent blank acceptable solution, the centrifugal laggard high performance liquid chromatography instrument of sample measures honokiol content.Parallelly do 6 increment product.According to following formulae discovery accumulation skin permeation rate (Q): Q=C
nv/M
0(C
n=C
1+ C
2+ C
3+ ... + C
n).In formula, Q is honokiol accumulation skin permeation rate, C
nbe the summation of the n-th sub-sampling and the honokiol concentration of each point in time sampling above, V is acceptance pool total liquid volume, M
0for the honokiol amount that skin is smeared.The free honokiol dissolved with 0.5% Tween 80 in contrast, carries out permeation test in vitro.The transdermal absorption factor of result display honokiol emulsifiable paste honokiol in 12h arrives 20% ~ 30%, and the free honokiol directly adopting 0.5% Tween 80 to dissolve under the same conditions in 12h the transdermal absorption factor of honokiol less than 10%, this display honokiol emulsifiable paste of the present invention improves the skin transdermal absorption factor of honokiol, is conducive to medicine and plays better therapeutical effect.、
The purposes of test example 1 honokiol in treatment hyperkeratinization and keratosa dermatosis
Test method 1: test grouping is carried out to the K14-VEGF transgenic homozygote psoriasis mice screened and FVB/N mice and is divided into 13 groups at random, often organize 4, be respectively the 1st group of .FVB/N mice (remarks: this mice is the wild-type mice kind of K14-VEGF transgenic mice); 2nd group. model group 1, smear normal saline 2 time-of-week; 3rd group. model group 2, smear normal saline 4 time-of-week; 4th group. model group 3, smear normal saline 6 time-of-week; 5th group. bare substrate group 1, smear bare substrate 2 time-of-week; 6th group. bare substrate group 2, smear bare substrate 4 time-of-week; 7th group. bare substrate group 3, smear bare substrate 6 time-of-week; 8th group. middle dosage honokiol group 1, smear 0.5% honokiol 2 time-of-week; 9th group. middle dosage honokiol group 2, smear 0.5% honokiol 4 time-of-week; 10th group. middle dosage honokiol group 3, smear 0.5% honokiol 6 time-of-week; 11st group. low dosage honokiol group, smear 0.1% honokiol 4 time-of-week; 12nd group. high dose honokiol group, smear 1% honokiol 4 time-of-week; 13rd group. positive drug group, smear tretinoin emulsifiable paste 4 time-of-week.Except the 1st group, all the other respectively group all pick respective medicaments uniformity with cotton swab to smear K14-VEGF transgenic mice hard of hearing, smear 1 every day.According to the treatment termination time, collecting sample carries out coherent detection.
Respectively organize mouse ear imaging results when treating 4 weeks and see Fig. 1, show honokiol and obviously inhibit that K14-VEGF transgenic mice ear is psoriasic to develop, at dose dependent.Low dosage honokiol is slightly better than positive drug effect, all can improve psoriasic symptom; Middle and high dosage honokiol therapeutic effect is better, and high dose honokiol is slightly better than middle dosage honokiol.Treat 2,4,6 weeks mouse ear H & E coloration results and see Fig. 2-4, showing honokiol makes K14-VEGF transgenic mice ear epidermis edema greatly alleviate, spinous layer is greatly thinning, and parakeratosis alleviates greatly, is dose-dependence to psoriasis treatment effect.
Test method 2: hard of hearing with 5% propranolol emulsifiable paste uniform application Cavia porcellus both sides, every day 2 times, continuous 3 weeks, sets up the hard of hearing psoriasis animal model of Cavia porcellus.Dosage in honokiol is selected to carry out the pharmacodynamic evaluation of this model, Cavia porcellus after modeling is divided into 5 groups at random, often organize 4, male and female half and half, be respectively first group. Normal group, second group. model group, the 3rd group. bare substrate group, 4th group of .0.5% honokiol group, the 5th group. positive drug tretinoin emulsifiable paste group.Except normal group, other each group respectively at the administration of Cavia porcellus bilateral hard of hearing skin uniform application, model group gives normal saline group, smears 2 every day, successive administration 12 days.After last coating, the neck that breaks next day puts to death Cavia porcellus, and depart from baseline clip Cavia porcellus ear along auricle and put into 4% neutral paraformaldehyde rapidly and fix, paraffin embedding, H & E dyes, basis of microscopic observation.The results are shown in Figure 5, show honokiol and psoriasis Cavia porcellus ear horny layer can be made significantly thinning, hyperkeratinization significantly lightens, Granulosa cells becomes to embark on journey continuously distribution, spinous layer is thinning, and basal cell trochanterellus becomes smooth and dermal papilla rises into shaft-like less, and effect is better than positive drug.
Conclusion: utilize honokiol to have and make the effects such as horny layer is significantly thinning, hyperkeratinization significantly lightens, therefore, may be used for treating the keratosa dermatosis with the thickening symptom of horny layer, as ichthyosis, getting blisters property epidermolysis bullosa disease, psoriasis, coloring xeroderma, follicular keratosis, porokeratosis of Mibelli, keratosis palmaris et plantaris, Progressive symmetric erythrokeratodermia symmetry erythema cuticle disease, menopause cuticle disease, the absent-mindedness of exfoliative cutin disease, avitaminosis, scleroderma etc.
Test example 2 honokiol has the purposes of immunosuppressive action aspect
Test method: scheme is with the test method 1 of embodiment 3.In transgenic cow tinea mice serum, the testing result of the cytokine such as IFN-γ, TNF-α, IL-2, IL-4 and IL-10 is shown in Fig. 6-9, show honokiol and can reduce IFN-γ in serum, TNF-α secretion level, and on IL-2, IL-4 and IL-10 almost without impact.In mouse ear tissue, IFN-γ, TNF-α gene expression dose the results are shown in Figure 10, show the mrna expression level that honokiol can suppress IFN-γ, TNF-α.Honokiol affects result of the test in table 1 to mouse T lymphocyte, and showing honokiol is by lowering CD3 in lymphocyte
+t cell, CD4
+the expression of T cell, the expression of lowering Th1 cell further plays immunosuppressive action, in particular for playing the psoriasic immunosuppressive action for the treatment of.
Table 1 honokiol is on the impact of CD3, CD4, CD8, Th1, Th2 cellular expression rate in mouse spleen T lymphocyte
(remarks: *, P<0.05vs model; *, P<0.01vs model)
Test example 3 sets forth the concrete mechanism of honokiol angiogenesis inhibitor
Test method: scheme is with the test method 1 of embodiment 3.Respectively organizing mouse ear when treating 4 weeks organizes the expression of E-selectin, ICAM-1, VCAM-1 to see Figure 11-13, shows honokiol and can suppress the expression of the adhesion factor that E-selectin, ICAM-1, VCAM-1 are relevant to angiogenesis in mouse ear tissue and play the psoriasic effect for the treatment of.Respectively organize mouse ear when treating 4 weeks to organize VEGFR-2, Akt, ERK1/2, p38 expression and the phosphorylation level corresponding to them to show honokiol can to lower VEGFR-2 expression and VEGFR-2, Akt, ERK1/2, p38 phosphorylation level simultaneously, and on kt, ERK1/2, p38 expression without impact.Concrete outcome is shown in Figure 14-18.Disclose honokiol by suppressing VEGFR-2 expression and VEGFR-2, Akt, ERK1/2, p38 phosphorylation level to play blood vessel formation against function and then to play the psoriasic effect for the treatment of.
To sum up, honokiol has the effect improving more by force hyperkeratinization, immunosuppressant and angiogenesis inhibitor, can utilize the keratosa dermatosis of above-mentioned URIN Treatment, namely honokiol or its pharmaceutically acceptable salt can prevent or treat keratosa dermatosis, especially curing psoriasis Be very effective.
Claims (18)
1. honokiol or its pharmaceutically acceptable salt treat the purposes in the medicine of the hyperkeratinization symptom in keratosa dermatosis in preparation, it is characterized in that: described keratosa dermopathic hyperkeratinization symptom is ichthyotic hyperkeratinization symptom, the hyperkeratinization symptom of getting blisters property epidermolysis bullosa disease, the hyperkeratinization symptom of coloring xeroderma, the hyperkeratinization symptom of follicular keratosis, the hyperkeratinization symptom of porokeratosis of Mibelli, the hyperkeratinization symptom of keratosis palmaris et plantaris, the hyperkeratinization symptom of Progressive symmetric erythrokeratodermia symmetry erythema cuticle disease, menopause cuticle disease hyperkeratinization symptom, the hyperkeratinization symptom of exfoliative cutin absent-mindedness disease, the hyperkeratinization symptom of avitaminosis, any one in sclerodermatous hyperkeratinization symptom.
2. purposes according to claim 1, is characterized in that: described honokiol pharmaceutically acceptable salt is honokiol disodium salt, honokiol di-potassium.
3. honokiol disodium salt, the honokiol di-potassium purposes in the medicine of the psoriasic hyperkeratinization symptom of preparation treatment.
4. the purposes according to any one of claim 1-3, is characterized in that: described medicine is external preparation.
5. purposes according to claim 4, is characterized in that: described external preparation be in emulsifiable paste, varnish, liniment, lotion any one.
6. purposes according to claim 4, is characterized in that: described external preparation be with honokiol or its pharmaceutically acceptable salt for main active, add pharmaceutics and commonly use the external preparation that adjuvant makes.
7. purposes according to claim 6, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%.
8. purposes according to claim 7, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 6%.
9. purposes according to claim 7, is characterized in that: also containing percentage by weight in external preparation is 0.001-0.05% antiseptic; Its percentage by weight is
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%
Antiseptic 0.001%-0.05%.
10. purposes according to claim 9, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 6%
Antiseptic 0.001%-0.05%.
11. purposes according to claim 4, is characterized in that: described external preparation be with honokiol or its pharmaceutically acceptable salt for sole active agent, add pharmaceutics and commonly use the external preparation that adjuvant makes.
12. purposes according to claim 11, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%.
13. purposes according to claim 12, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 6%.
14. purposes according to claim 12, is characterized in that: also containing percentage by weight in external preparation is 0.001-0.05% antiseptic; Its percentage by weight is
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 10%
Antiseptic 0.001%-0.05%.
15. purposes according to claim 14, is characterized in that: the component containing following weight percentage ratio in external preparation:
Honokiol or its pharmaceutically acceptable salt 0.01% ~ 10%
Highly effective skin penetration enhancer 0.1% ~ 6%
Antiseptic 0.001%-0.05%.
16. purposes according to any one of claim 7-10,12-15, is characterized in that: described highly effective skin penetration enhancer is one in water-solubleazone, propylene glycol, Mentholum or its mixture.
17. purposes according to any one of claim 7-10,12-15, is characterized in that: adjuvant that also commonly use containing external preparation in external preparation, conventional amount used.
18. purposes according to claim 16, is characterized in that: adjuvant that also commonly use containing external preparation in external preparation, conventional amount used.
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| 厚朴酚与和厚朴酚药理作用的研究进展;王立清等;《中草药》;20051031;第36卷(第10期);参见第1591-1594页 * |
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