CN107296809A - A kind of externally-applied medicinal composition for treating psoriasis - Google Patents
A kind of externally-applied medicinal composition for treating psoriasis Download PDFInfo
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- CN107296809A CN107296809A CN201610233451.9A CN201610233451A CN107296809A CN 107296809 A CN107296809 A CN 107296809A CN 201610233451 A CN201610233451 A CN 201610233451A CN 107296809 A CN107296809 A CN 107296809A
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- Prior art keywords
- tazarotene
- externally
- urea
- psoriasis
- medicinal composition
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- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 claims abstract description 40
- 229960000565 tazarotene Drugs 0.000 claims abstract description 40
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000004202 carbamide Substances 0.000 claims abstract description 31
- 239000006071 cream Substances 0.000 claims abstract description 16
- 239000000499 gel Substances 0.000 claims abstract description 7
- 239000002674 ointment Substances 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 4
- 239000002552 dosage form Substances 0.000 claims abstract description 3
- 238000011282 treatment Methods 0.000 claims description 14
- 230000000694 effects Effects 0.000 abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
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- ZTVIKZXZYLEVOL-DGKWVBSXSA-N 2-hydroxy-2-phenylacetic acid [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] ester Chemical group C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-DGKWVBSXSA-N 0.000 description 4
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- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- 206010048768 Dermatosis Diseases 0.000 description 2
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- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
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- 235000019388 lanolin Nutrition 0.000 description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
- 229940100462 pegoxol 7 stearate Drugs 0.000 description 2
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- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 102100028999 High mobility group protein HMGI-C Human genes 0.000 description 1
- 101000986379 Homo sapiens High mobility group protein HMGI-C Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000461895 Keratosa Species 0.000 description 1
- 206010062315 Lipohypertrophy Diseases 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 241000669298 Pseudaulacaspis pentagona Species 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
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- 206010052428 Wound Diseases 0.000 description 1
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- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960002311 dithranol Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
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- 230000002500 effect on skin Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
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- 238000011866 long-term treatment Methods 0.000 description 1
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- 230000003020 moisturizing effect Effects 0.000 description 1
- 208000028261 multifactorial inheritance Diseases 0.000 description 1
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- 235000020824 obesity Nutrition 0.000 description 1
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- 231100000915 pathological change Toxicity 0.000 description 1
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- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000011450 sequencing therapy Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229960004907 tacalcitol Drugs 0.000 description 1
- BJYLYJCXYAMOFT-RSFVBTMBSA-N tacalcitol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@@H](O)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C BJYLYJCXYAMOFT-RSFVBTMBSA-N 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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- 229940126702 topical medication Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
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- 230000009385 viral infection Effects 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of externally-applied medicinal composition for treating psoriasis, its dosage form includes cream, ointment and gel.The pharmaceutical composition contains 0.05% ~ 0.1%（w/w）Tazarotene, 10% ~ 20%（w/w）Urea and pharmaceutically acceptable excipient.Pharmaceutical composition of the present invention has significant curative effect to psoriasis, and security is good.
Description
Technical field
The present invention relates to a kind of externally-applied medicinal composition for treating psoriasis.It is more particularly related to a kind of externally-applied medicinal composition containing tazarotene and urea.
Background technology
Psoriasis, is commonly called as psoriasis, is a kind of common chronic inflammatory dermatoses easily recurred with characteristic skin damaged, it belongs to disease of multifactorial inheritance, can be by a variety of excitation conditions（Such as wound, infection, medicine）Induced in susceptible individual.Pathological change is skin keratinocytes hyperplasia and breaks up incomplete, inflammatory cell infiltration, dermal vascular expansion etc..Clinical manifestation is based on erythema, the scales of skin that peel off；Skin damaged is the red papules and macula differed in size, above has multilayer to dry white silver bits, patient often very itch by sense.Can occur at any position of human body, it is relatively conventional to stretch side with scalp, four limbs, aggravates in the winter time more.Harm：Psoriatic is except feeling affected part unsightly, in addition to itch, pain, be also easy to cause other complication, such as：Tumour, mental disease, hypertension, diabetes, heart disease etc..
The provinces and cities' Epidemiologic Study of Psoriasis result of China 6 was shown in 2010, China's psoriasis illness rate is 0.47%, illness rate asexuality difference.The factors such as psoriasis illness rate and race, geographical position, environment are relevant.Inducement is probably heredity（Key factor, including bone-marrow transplantation etc.）, infection（Bacterium, virus infection etc.）, psychoneural factor and other（Such as, obesity, tobacco and wine, poor eating habits, drug induccd etc.）.Onset of psoriasis can be at any age, and onset peak is between 15 ~ 30 years old.
Psoriasis vulgaris is clinically most commonly seen, and typical performance is the erythema that boundary understands, shape size differs, and around has inflammatory blush, has infiltration to thicken, the surface covering multilayer silvery white scales of skin that peel off.The treatment of current psoriasis vulgaris is divided into local topical medication, physical treatment, Systemic administration（Including immunodepressant, biological agent etc.）, conjoint therapy, sequential therapy.Wherein local application includes：Keatolytics（Urea, salicylic acid, lactic acid etc.）, immunodepressant（Tacrolimus paste）, vitamin D derivative（Calcipotriol, Tacalcitol etc.）, tretinoin（Tretinoin emulsifiable paste, tazarotene cream/gel etc.）, Dithranol, glucocorticoid etc..
With the growth of onset of psoriasis rate, the whole world is to the research and development of psoriasis new drug also in heating.Some are used for the monoclonal antibody for treating psoriasis also in burning hot research and development and listing, but the price of this kind of medicine data of safety long-term due to lacking and costliness at present, it is not easy to widely use.At present the first-line drug of country's psoriasis vulgaris local treatment still in/potent glucocorticoid, tazarotene, its salts（Also known as " Calcipotriol "）Based on.But because the treatment of psoriasis needs long-term prescription, the adverse reaction for easily causing many complication and steroids is used for a long time in glucocorticoid（Such as：Cause the hyperfunction syndrome of cortex hormone function, moon shaped face occur, the symptom such as buffalo hump；Induce or aggravate infection and ulcer；Induce hypertension, mental disease etc.）, therefore the long term maintenance therapy using glucocorticoid as psoriasis is not preferable selection.
Tazarotene is the precursor medicine of the V-A acidic of external preparation for skin, belongs to third generation tretinoin medicines, with the effect such as the differentiation of regulation epidermal cell and propagation and reduction inflammation.First and second generation tretinoin medicines are because, containing multiple alternate single, double keys, configuration is variable, can be combined with a variety of Retinoic acid receptors, extensive physiological effect be produced, while also there is more adverse reaction in chemical constitution.Isomers is not present in the chemical constitution of tazarotene, is converted into tazarotene acid by quickly taking off ester effect in animal and human body, the activated product can be combined to relative selectivity with β the and γ hypotypes of Retinoic acid receptor, and then targeting is in pathological tissues（Such as the keratinocyte of psoriasis）, only activation produces the relational approach of curative effect, so as to minimize adverse reaction.
It is reported that, tazarotene clinical efficacy is similar to lidex, although it is rapid-action not as corticosteroid, but its clinical relieving period is longer, disable after 12 weeks, recurrence rate only 18%, and corticosteroid person recurrence rate is used up to 55%, and the generalized effects produced during long-term treatment without corticosteroid and Calcipotriol prolonged application.
There are some researches show there was no significant difference for the effective percentage of tazarotene and its salts treatment psoriasis vulgaris, but skin damaged clearance rate is less than the latter, but the common adverse reaction of Calcipotriol --- local excitation seriously limits its application：Using the patient of Calcipotriol such reaction can occur for about 15%-20%, and 2%-3% patient has to stop treatment.Tazarotene also has local irritation, after external application, and main adverse reaction is itch, erythema and scorching hot；The excitant of its creme is less than gel.
Emollient, keatolytics（Urea, salicylic acid, lactic acid etc.）Hyperkeratinization patch skin damaged to plumpness is effective.Urea in emollient is common composition in preparation for external application to skin, and it can make keratoprotein dissolving denaturation, promote cuticula aquation, so that skin emolliency, prevents dry and cracked, while having the effect such as antipruritic, antibacterial concurrently, and can increase the penetrability of drug percutaneous skin.Urea is applied to psoriatic, affected part epidermal hyperplasia and pruritis can be mitigated；Urea is as keatolytics, and the scales of skin that peel off that can be also thickened by removing makes other drugs enter skin, increases permeability.
According to the mechanism of action, tazarotene and keatolytics（Urea, salicylic acid, lactic acid etc.）Combination can promote skin damaged to remove, and promote illing skin to recover and heal, accelerate the healing process of the keratinization diseases such as psoriasis, acne, ichthyosis.
Tazarotene and urea drug combination, can both be improved the hyper-proliferative of affected part horn cell by tazarotene, promote inflammatory resolution；The scales of skin that peel off that removing is thickened, antipruritic, moisturizing and antibacterial action can be reached by urea again；Externally used compound preparation is made in both, and the skin that urea may additionally facilitate tazarotene absorbs, and a small amount of tazarotene is can reach the drug effect using larger dose, so as to reach raising drug effect, reduce the effect of its adverse reaction.The present inventor has found that the compound external-use preparation of tazarotene and urea composition is a kind of medicine of new, efficient, safe treatment abnormal cutaneous keratinization by in-depth study.It can be clinically used for treating the multiple dermatosis such as psoriasis and acne.
Through retrieval, up to the present, not yet there is the report that psoriasis is treated with this compound preparation.
The content of the invention
It is a kind of using tazarotene and urea as the externally used compound preparation of main active it is an object of the invention to develop, provide a kind of safe and efficient local treatment medicine for keratosa dermatosis patient.
The invention provides a kind of externally-applied medicinal composition for treating psoriasis, contain 0.03% ~ 0.2%（w/w）Tazarotene, 5% ~ 30%（w/w）Urea, and other pharmaceutically acceptable excipient.
Preferred percentage composition of the tazarotene in the externally-applied medicinal composition is 0. 05% ~ 0.1%（w/w）.
Preferred percentage composition of the urea in the externally-applied medicinal composition is 5% ~ 20%（w/w）, more preferred percentage composition is 10% ~ 20%（w/w）.
Other compositions in above-mentioned externally-applied medicinal composition are pharmaceutically acceptable excipient, such as：Carrier, preservative, emulsifying agent, stabilizer, pH adjusting agent etc..
The above-mentioned externally-applied medicinal composition that the present invention is provided, its dosage form includes cream, ointment and gel.
The preparation for the externally-applied medicinal composition that the present invention is described is carried out according to the known method for being used to prepare cream, ointment and gel.
The externally-applied medicinal composition that the present invention is described, available for treatment psoriasis, acne, ichthyosis and other angling dermatoses.
Embodiment
The present invention is elaborated by embodiment below, it should be understood, however, that, these embodiments, which are only used for specifically describing in more detail, to be used, and is not to be construed as limiting the present invention in any form.
Embodiment 1
Ointment（Unit：g）：
| Tazarotene | 0.05 |
| Urea | 10 |
| Hexadecanol | 0.5 |
| Albolene | 9.5 |
| Lanolin | 2.0 |
| Stearic acid | 12 |
| Propane diols | 10 |
| Ethanol | 10 |
| Glycerine | 2 |
| Triethanolamine | 1.0 |
| Nepal's methyl esters | 0.2 |
| Nepal's propyl ester | 0.05 |
| Purified water | Add to 100 |
Preparation method is as follows：
Urea is dissolved in standby in the water for be heated to 80-85 DEG C；Stirring adds propane diols, glycerine, triethanolamine, Nepal's methyl esters, Nepal's propyl ester into purified water respectively again（Aqueous phase）；See that albolene, hexadecanol, lanolin, stearic acid stir and be heated to 80-85 DEG C respectively（Oil phase）；Aqueous phase is added into oil phase and the tazarotene that lower addition ethanol dissolves is stirred continuously, and is stirred continuously, room temperature is slowly cooled to.
Embodiment 2
Ointment（Unit：g）
| Tazarotene | 0.1 |
| Urea | 15 |
| Octadecyl alcolol | 7 |
| Albolene | 15 |
| Atoleine | 5 |
| Glycerin monostearate | 3 |
| Stearic acid | 2 |
| Propane diols | 10 |
| Ethanol | 15 |
| Glycerine | 5 |
| Triethanolamine | 1.0 |
| Nepal's methyl esters | 0.2 |
| Nepal's propyl ester | 0.05 |
| Purified water | Add to 100 |
Preparation method is as follows：
Tazarotene, urea are dissolved in standby in ethanol and propylene glycol solution；Stirring adds triethanolamine, glycerine, Nepal's methyl esters, Nepal's propyl ester into purified water respectively again, is heated to 80-85 DEG C（Aqueous phase）；Cetostearyl alcohol, albolene, atoleine, glycerin monostearate, stearic acid are heated to 80-85 DEG C（Oil phase）；Aqueous phase is added into oil phase formation emulsifiable paste, drug solution is added and continues to emulsify, and is stirred continuously, room temperature is slowly cooled to.
Embodiment 3
Emulsifiable paste（Unit：g）：
| Tazarotene | 0.05 |
| Urea | 10 |
| Pegoxol 7 stearate | 10 |
| Cetostearyl alcohol | 3 |
| Atoleine | 8 |
| Dibutyl hydroxy toluene（BHT） | 0.1 |
| Nepal's methyl esters | 0.2 |
| Nepal's propyl ester | 0.05 |
| Propane diols | 10 |
| Ethanol | 10 |
| Triethanolamine | 1.0 |
| Purified water | Add to 100 |
Preparation method is as follows：
Tazarotene, urea are dissolved in ethanol and propylene glycol solution, dibutyl hydroxy toluene is added（BHT）, triethanolamine, Nepal's methyl esters, Nepal's propyl ester, purified water stir and be heated to 80-85 DEG C（Aqueous phase）；Cetostearyl alcohol, atoleine, pegoxol 7 stearate are heated to 80-85 DEG C（Oil phase）；Aqueous phase is added into oil phase formation emulsifiable paste, and is stirred continuously, room temperature is slowly cooled to.
Embodiment 4
Emulsifiable paste（Unit：g）：
| Tazarotene | 0.1 |
| Urea | 10 |
| Stearyl alcohol | 10 |
| Albolene | 15 |
| Glycerin monostearate | 2 |
| Polyoxyethylene sorbitan monoleate | 1 |
| Ethanol | 10 |
| Propane diols | 12 |
| Triethanolamine | 1.0 |
| Nepal's propyl ester | 0.1 |
| Purified water | Add to 100 |
Preparation method is as follows：
Tazarotene, urea are dissolved in ethanol and propylene glycol solution, triethanolamine, Nepal's propyl ester, polyoxyethylene sorbitan monoleate, purified water is added and is heated to 80-85 DEG C（Aqueous phase）；Stearyl alcohol, albolene, glycerin monostearate are heated to 80-85 DEG C（Oil phase）；Aqueous phase is added into oil phase formation emulsifiable paste, and is stirred continuously, room temperature is slowly cooled to.
Embodiment 5
Emulsifiable paste（Unit：g）
| Tazarotene | 0.05 |
| Urea | 10 |
| Isopropyl myristate | 10 |
| Glycerin monostearate | 4 |
| Hexadecanol | 10 |
| Octadecyl alcolol | 10 |
| Peregal-O | 1 |
| Ethanol | 10 |
| Propane diols | 10 |
| Triethanolamine | 1.0 |
| Nepal's ethyl ester | 0.2 |
| Purified water | Add to 100 |
Preparation method is as follows：
Tazarotene, urea are dissolved in ethanol and propylene glycol solution, triethanolamine, Nepal's ethyl ester, peregal-O, purified water is added and is heated to 80-85 DEG C（Aqueous phase）；Isopropyl myristate, hexadecanol, octadecyl alcolol, glycerin monostearate are heated to 80-85 DEG C（Oil phase）；Aqueous phase is added into oil phase formation emulsifiable paste, and is stirred continuously, room temperature is slowly cooled to.
Embodiment 6
Gel（Unit：g）：
| Tazarotene | 0.1 |
| Urea | 10 |
| Carbopol 941 | 3 |
| Ethanol | 20 |
| Propane diols | 10 |
| Glycerine | 10 |
| Triethanolamine | 2 |
| Nepal's ethyl ester | 0.1 |
| Purified water | Add to 100 |
Preparation method is as follows：
Carbomer is sprinkled into appropriate purified water, stirring is swelled it, adds glycerine, Nepal's ethyl ester stirring and dissolving, continued dropwise addition triethanolamine and gel-type vehicle is made；Tazarotene, urea are dissolved in ethanol and propylene glycol solution, then are stirred continuously addition gel-type vehicle, stirs evenly and produces.
The pharmacodynamics trial test of the medicine composite for curing psoriasis of the present invention of embodiment 7
Experimental animal：BA LB/c female mices
Trial drug：5% imiquimod cream（Animal model is used）, the pharmaceutical composition of embodiment 4（Containing 0.1% tazarotene and 10% urea）It is used as experiment medication；0.1% tazarotene cream is used as positive control drug.
Test method：The BABL/c mouse 8 of selection 6-8 weeks, are randomly divided into 4 groups, every group 2.Back is lost hair or feathers, area about 2cm × 1.5cm, and by group sub-cage rearing, numbering, per 2, cage, is normally fed with water and mouse feed daily.Distilled water is smeared daily without hair-fields in 1st group of back（It is used as Normal group）, 2-4 groups（Modeling group）Back is coated with 5% imiquimod cream, 60mg/ days, continuous 6 days without hair-fields.
After modeling success, 3 model groups（2-4 groups）Still need to every two day morning smear imiquimod cream once, to keep the stability of psoriasis model, it is to avoid spontaneous remission.
Dosage regimen：Every night smears corresponding water or medicine at the back of each group mouse without hair-fields：To the 1st group（Normal group）With the 2nd group（Model control group）Distilled water is smeared, to the pharmaceutical composition of the 3rd group of smearing embodiment 4, the 4th group of tazarotene cream of smearing 0.1%, continuous 2 weeks.Observe erythema scales of skin that peel off situation of change at every Bearing Mice Life sign, observation mouse back skin damaged.
Result of the test：
Treat after 2 weeks, the 1st group of skin of back is normal, there is hair growth；The 2nd group of erythema scales of skin that peel off is not improved before relatively treating；3rd group and the 4th group of erythema scales of skin that peel off have taken a turn for the better earlier above, wherein the 3rd group of scales of skin that peel off thickness substantially tails off thinning earlier above, and these improvement are also significantly better than the 4th group.
The tazarotene cream of embodiment 8 and urea cream drug combination are compared with the curative effect of tazarotene cream folk prescription and adverse reaction
Patient：The common psoriasis in plaques patient that unused curing psoriasis medicine is treated in 2 weeks.
Observation index：Patient's erythema, the scales of skin that peel off, skin infiltration are recorded when before treatment with follow-up in detail（Thickness）Situation of change, is scored by PASI；Follow-up records the adverse reaction situation of patient simultaneously.
Implementation：
Treatment group：Daytime urea cream（10%）2 times/d, every night external application tazarotene cream（0.1%）1 time；It is used in conjunction 8 weeks, follow-up during medication.
Control group：Only simple external application tazarotene cream（0.1%）, 1 time every night；It is used in conjunction 8 weeks, follow-up during medication.
Comparitive study：Treatment group's cure rate is 83.3%, and control group cure rate is 66.7%.
Adverse reaction：Compared with control group, the adverse reaction for the treatment of group significantly mitigates.Adverse reaction shows as spontaneous remission or disappearance after itch, slight drying, furfur, erythema and burn feeling, last for several minutes, does not influence to continue medication.
Claims (5)
1. a kind of externally-applied medicinal composition for treating psoriasis, it is characterised in that this externally-applied medicinal composition contains tazarotene, urea and other pharmaceutically acceptable excipient.
2. externally-applied medicinal composition according to claim 1, percentage composition of the tazarotene in the pharmaceutical composition is 0.05% ~ 0.1%（w/w）.
3. externally-applied medicinal composition according to claim 1 or 2, percentage composition of the urea in the pharmaceutical composition is 5% ~ 20%（w/w）, effective content is 10% ~ 20%（w/w）.
4. the externally-applied medicinal composition according to any one of claim 1 ~ 3, its dosage form includes cream, ointment and gel.
5. the externally-applied medicinal composition according to any one of claim 1 ~ 4, available for treatment psoriasis vulgaris.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610233451.9A CN107296809A (en) | 2016-04-15 | 2016-04-15 | A kind of externally-applied medicinal composition for treating psoriasis |
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|---|---|---|---|
| CN201610233451.9A CN107296809A (en) | 2016-04-15 | 2016-04-15 | A kind of externally-applied medicinal composition for treating psoriasis |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1478478A (en) * | 2002-12-06 | 2004-03-03 | 重庆华邦制药股份有限公司 | Medicinal composition for treating psoriasis |
| US20050002878A1 (en) * | 2001-10-05 | 2005-01-06 | Pascal Lefrancois | Use of tazarotene for preparing a nail varnish for treating and/or preventing psoriasis and nail varnish containing same |
| CN1823728A (en) * | 2005-12-16 | 2006-08-30 | 天津南大日月生物科技有限公司 | Fast film forming medical film coating liquid possessing antiseptic and/or treating action |
| ES2362066A1 (en) * | 2009-11-23 | 2011-06-28 | Juan Barroso Abril | Combined preparation for the treatment of psoriasis. (Machine-translation by Google Translate, not legally binding) |
-
2016
- 2016-04-15 CN CN201610233451.9A patent/CN107296809A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050002878A1 (en) * | 2001-10-05 | 2005-01-06 | Pascal Lefrancois | Use of tazarotene for preparing a nail varnish for treating and/or preventing psoriasis and nail varnish containing same |
| CN1478478A (en) * | 2002-12-06 | 2004-03-03 | 重庆华邦制药股份有限公司 | Medicinal composition for treating psoriasis |
| CN1823728A (en) * | 2005-12-16 | 2006-08-30 | 天津南大日月生物科技有限公司 | Fast film forming medical film coating liquid possessing antiseptic and/or treating action |
| ES2362066A1 (en) * | 2009-11-23 | 2011-06-28 | Juan Barroso Abril | Combined preparation for the treatment of psoriasis. (Machine-translation by Google Translate, not legally binding) |
Non-Patent Citations (1)
| Title |
|---|
| MICHAEL E. HERBIG ET AL.: "Correlation of hydrotropic solubilization by urea with logD of drug molecules and utilization of this effect for topical formulations", 《EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》 * |
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Application publication date: 20171027 |