阅读说明：本技术 包含至少一种局部唑抗真菌物质的用于局部使用的药物组合物 (Pharmaceutical composition for topical use comprising at least one topical azole antifungal substance ) 是由 C·布考特 A·丹尼斯 塞维琳·西古拉尼 于 2020-04-01 设计创作，主要内容包括：披露了一种用于局部使用的药物组合物,其呈油包水乳液的形式,对于100％的其重量,包含：-按重量计从0.3％至5％的至少一种局部唑抗真菌物质；-按重量计从60％至90％的胶凝水相(Al)；-按重量计从9.7％至35％的脂肪相(A2),该脂肪相包含至少一种油和乳化体系,该乳化体系包含至少一种乳化表面活性剂(S1)和至少一种乳化表面活性剂(S2)的组合,该乳化表面活性剂(S1)选自由烷基多糖苷组合物以及烷基多糖苷和脂肪醇组合物组成的组的元素,该乳化表面活性剂(S2)选自由聚甘油酯、烷氧基化聚甘油酯、聚二醇聚羟基硬脂酸酯、聚甘油聚羟基硬脂酸酯、以及烷氧基化聚甘油聚羟基硬脂酸酯组成的组的元素。(A pharmaceutical composition for topical use is disclosed, in the form of a water-in-oil emulsion comprising, for 100% of its weight: -from 0.3 to 5% by weight of at least one topical azole antifungal substance; -from 60 to 90% by weight of a gelled aqueous phase (Al); -from 9.7 to 35% by weight of a fatty phase (a2) comprising at least one oil and an emulsifying system comprising a combination of at least one emulsifying surfactant (S1) and at least one emulsifying surfactant (S2), the emulsifying surfactant (S1) being selected from elements of the group consisting of alkyl polyglycoside compositions and alkyl polyglycoside and fatty alcohol compositions, the emulsifying surfactant (S2) being selected from elements of the group consisting of polyglycerol esters, alkoxylated polyglycerol esters, polyglycol polyhydroxystearate, polyglycerol polyhydroxystearate, and alkoxylated polyglycerol polyhydroxystearate.)

1. A pharmaceutical composition (E1) for topical use, in the form of a water-in-oil emulsion comprising, for 100% of its weight:

-from 0.3 to 5% by weight of at least one topical azole antifungal substance;

-from 60 to 90% by weight of a gelled aqueous phase (a 1);

-from 9.7 to 35% by weight of a fatty phase (a2) comprising at least one oil and an emulsifying system comprising a combination of at least one emulsifying surfactant (S1) and at least one emulsifying surfactant (S2), the emulsifying surfactant (S1) being selected from elements of the group consisting of a combination of alkylpolyglycosides, and a combination of alkylpolyglycosides and fatty alcohols, the emulsifying surfactant (S2) being selected from elements of the group consisting of polyglycerol esters, alkoxylated polyglycerol esters, polyglycol polyhydroxystearates, polyglycerol polyhydroxystearates, and alkoxylated polyglycerol polyhydroxystearates.

2. The pharmaceutical composition (E1) for topical use according to claim 1, wherein the gelling water comprises, relative to 100% of its weight:

from 0.5 to 10% by weight of a crosslinked Anionic Polyelectrolyte (AP),

-from 90 to 99.5% by weight of water.

3. The pharmaceutical composition (E1) for topical use according to claim 2, characterized in that the crosslinked Anionic Polyelectrolyte (AP) comprises a proportion of greater than or equal to 25 mol% of monomer units derived from 2-methyl-2- [ (1-oxo-2-propenyl) amino ] -1-propanesulfonic acid in free acid or partially or fully salified form.

4. A pharmaceutical composition (E1) for topical use according to one of claims 1 to 3, characterized in that the topical azole antifungal substance is an element in neutral form or in salt form selected from the group consisting of: is represented by the formula (Ia)₁) R enantiomer of (Ia) (CAS number 91487-85-3) or formula (Ia)₂) (RS) -1- [ phenyl (4-phenylphenyl) methyl in the form of the S enantiomer of (CAS number 91487-86-4)]-1H-imidazole or bifonazole:

is of the formula (Ib)₁) R enantiomer of (a) or formula (Ib)₂) (RS) -1- {2- [ (4-chlorophenyl) methoxy group in the form of the S enantiomer of (1)]-2- (2, 4-dichlorophenyl) ethyl } -1H-imidazole (CAS number 27220-47-9) or econazole:

(R, S) -1- [2- (2, 4-dichlorophenyl) -2- { [4- (phenylsulfanyl) phenyl ] methoxy } ethyl ] -1H-imidazole or fenticonazole of formula (Ic) (CAS No. ═ 72479-26-6):

is of the formula (Id)₁) Form of the R enantiomer of (1)Is of the formula (Id)₂) (R, S) -1- {2- [ (2, 6-dichlorobenzyl) oxy in the form of the S enantiomer of (A)]-2- (2, 4-dichlorophenyl) ethyl } -1H-imidazole or isoconazole (CAS number 27523-40-6):

is of the formula (Ie)₁) In the form of the R enantiomer of (a) or in the form of (Ie)₂) 1- [4- (4- { [ (2R, 4S) -2- (2, 4-dichlorophenyl) -2- (1H-imidazol-1-ylmethyl) -1, 3-dioxolan-4-yl ] enantiomer of (a)]Methoxy } phenyl) piperazin-1-yl]Ethan-1-one or ketoconazole (CAS No. 65277-42-1):

is of the formula (If)₁) In the form of the R enantiomer of (a) or in the form of (If)₂) (R, S) -1- {2- [ (2, 4-dichlorobenzyl) oxy in the form of the S enantiomer of (A)]-2- (2, 4-dichlorophenyl) ethyl } -1H-imidazole or miconazole (CAS No. ═ 22916-47-8):

1- [ (Z) -2- [2- (4-chlorophenoxy) ethoxy ] -2- (2, 4-dichlorophenyl) -1-methylvinyl ] -1H-imidazole of formula (Ig) (CAS No. ═ 74512-12-2) or omoconazole:

(1Z) -N- [ (2, 4-dichlorobenzyl) oxy ] -1- (2, 4-dichlorophenyl) -2- (1H-imidazol-1-yl) ethanimine or oxiconazole of formula (Ih) (CAS No. ═ 64211-45-6):

(RS) -1- {2- [ (7-chloro-1-benzothien-3-yl) methoxy ] -2- (2, 4-dichlorophenyl) ethyl } -1H-imidazole or sertaconazole of formula (Ii) (CAS No. ═ 99592-32-2):

is of the formula (Ij)₁) In the form of the R enantiomer of (a) or in the form of (Ij)₂) (RS) -1- {2- [ (2-chlorothien-3-yl) methoxy ] in the form of the S enantiomer of (a)]-2- (2, 4-dichlorophenyl) ethyl } -1H-imidazole or tioconazole (CAS number 65899-73-2):

1- [ (2-chlorophenyl) (diphenyl) methyl ] -1H-imidazole of formula (Ik) or clotrimazole (CAS number ═ 23593-75-1)

5. A pharmaceutical composition (E1) for topical use according to one of claims 1 to 4, characterized in that the topical azole antifungal substance is selected from the elements of the group consisting of: formula (Ia)₁)、(Ia₂)、(Ib₁)、(Ib₂)、(Ic)、(Id₁)、(Id₂)、(Ie₁)、(Ie₂)、(If₁)、(If₂)、(Ig)、(Ih)、(Ii)、(Ij₁)、(Ij₂) Hydrochloride, phosphate, nitrate, propionate and citrate of the compounds of (i) and (Ik)。

6. The pharmaceutical composition (E1) for topical use according to one of claims 1 to 5, wherein the emulsifying surfactant (S1)₁) At least one alkylpolyglycoside composition (C) represented by the formula (VIII)₁) Consists of the following components:

R₁-O-(G)x-H (VIII)

wherein x represents a decimal number between 1.05 and 2.5, G represents a glucosyl group or an alpha, beta-D-glucopyranosyl group obtained by removing the hemiacetal hydroxyl group from an alpha, beta-D-glucopyranose, and R₁A group representing an element selected from the group consisting of: n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl and n-docosyl, said composition (C)₁) Consists of the following components: represented by the formula (VIII)₁)、(VIII₂)、(VIII₃)、(VIII₄) And (VIII)₅) A mixture of compounds represented by:

R₁-O-(G)₁-H(VIII₁)

R₁-O-(G)₂-H(VIII₂)

R₁-O-(G)₃-H(VIII₃)

R₁-O-(G)₄-H(VIII₄)

R₁-O-(G)₅-H(VIII₅)，

these compounds are in the respective molar ratio a₁、a₂、a₃、a₄And a₅So that:

-a₁+a₂+a₃+a₄+a₅the sum is equal to 1, and

-a₁+2a₂+3a₃+4a₄+5a₅the sum is equal to x.

7. The pharmaceutical composition (E1) for topical use according to one of claims 1 to 6, wherein the emulsifying surfactant (S1)₁) From at least one composition (C)₂) Composition (C) of the composition₂) Comprising for 100% of its weight:

-from 10 to 50% by weight of at least one alkylpolyglycoside composition (C) represented by formula (VIII)₁)：

R₁-O-(G)x-H (VIII)，

Wherein x represents a decimal number between 1.05 and 2.5, G represents a glucosyl group or an alpha, beta-D-glucopyranosyl group obtained by removing the hemiacetal hydroxyl group from an alpha, beta-D-glucopyranose, and R₁A group representing an element selected from the group consisting of: n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl, and n-docosyl, the composition consisting of: represented by the formula (VIII)₁)、(VIII₂)、(V1II₃)、(VIII₄) And (VIII)₅) A mixture of compounds represented by:

R1-O-(G)1-H(VIII1)

R1-O-(G)2-H(VIII2)

R1-O-(G)3-H(VIII3)

R1-O-(G)4-H(VIII4)

R1-O-(G)5-H(VIII5)

these compounds are in the respective molar ratio a₁、a₂、a₃、a₄And a₅So that:

-a₁+a₂+a₃+a₄+a₅the sum is equal to 1, and

-a₁+2a₂+3a₃+4a₄+5a₅the sum is equal to x; and

-from 90 to 50% by weight of at least one fatty alcohol of formula (IX):

R″₁-OH(IX)，

wherein R ″)₁A group representing an element selected from the group consisting of: n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl and n-docosyl, where R'₁Can be reacted with R₁The same or different.

8. The pharmaceutical composition (E1) for topical use according to one of claims 1 to 7, wherein the emulsifying surfactant (S1)₂) Consisting of at least one polyglycol polyhydroxystearate represented by the formula (XII):

wherein y2 represents an integer of 2 or more and 50 or less, R₄Represents a hydrogen atom, a methyl group or an ethyl group, and Z₂A group of formula (XIII):

wherein y'₂Denotes an integer greater than or equal to 0 and less than or equal to 10, more particularly greater than or equal to 1 and less than or equal to 10, and Z'₂Represents: a radical of formula (XIII) as defined above, in which Z'₂Can be reacted with Z₂The same or different; or a hydrogen atom.

9. The pharmaceutical composition (E1) for topical use according to one of claims 1 to 8, wherein the emulsifying surfactant (S1)₁) With the emulsifying surfactant (S)₂) Is greater than or equal to 1/4 and less than or equal to 1.

10. Pharmaceutical composition for topical use (E1) according to one of claims 1 to 9, characterized in that the composition is intended for the treatment of a human or animal mammal.

11. Pharmaceutical composition (E1) for topical use according to one of claims 1 to 9, for use in the treatment of mycoses of the skin, scalp, oral cavity and/or gynaecological system of a human or animal mammal.

12. Pharmaceutical composition (E1) for topical use according to one of claims 1 to 11, characterized in that it additionally comprises at least one or more auxiliary compounds selected from: foaming and/or detergent surfactants, thickening and/or gelling agents, stabilizers, film-forming compounds, solvents and cosolvents, hydrotropes, plasticizers, opacifying agents, pearlescing agents, superfatting agents, sequestering agents, chelating agents, antioxidants, perfumes, essential oils, preservatives, conditioning agents, deodorants, mineral fillers or pigments.