GB2188233A - Topical pharmaceutical compositions for treating vitiligo - Google Patents
Topical pharmaceutical compositions for treating vitiligo Download PDFInfo
- Publication number
- GB2188233A GB2188233A GB08628373A GB8628373A GB2188233A GB 2188233 A GB2188233 A GB 2188233A GB 08628373 A GB08628373 A GB 08628373A GB 8628373 A GB8628373 A GB 8628373A GB 2188233 A GB2188233 A GB 2188233A
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- United Kingdom
- Prior art keywords
- vitiligo
- mixture
- urea
- weight
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 206010047642 Vitiligo Diseases 0.000 title claims abstract description 18
- 239000012049 topical pharmaceutical composition Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 28
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract description 25
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 16
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims abstract description 15
- 229930002330 retinoic acid Natural products 0.000 claims abstract description 15
- 229960001727 tretinoin Drugs 0.000 claims abstract description 15
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 claims abstract description 14
- 229960002117 triamcinolone acetonide Drugs 0.000 claims abstract description 14
- 239000004202 carbamide Substances 0.000 claims abstract description 13
- 229940031955 anhydrous lanolin Drugs 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000007764 o/w emulsion Substances 0.000 claims abstract description 5
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 12
- 229960004889 salicylic acid Drugs 0.000 claims description 12
- 229940045136 urea Drugs 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 239000000839 emulsion Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 235000013871 bee wax Nutrition 0.000 claims description 5
- 239000012166 beeswax Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000002191 fatty alcohols Chemical class 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 239000012188 paraffin wax Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- -1 anhydrous lanolin Chemical compound 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 description 19
- 239000013543 active substance Substances 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 206010000496 acne Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001530 keratinolytic effect Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000009291 secondary effect Effects 0.000 description 3
- 229940100611 topical cream Drugs 0.000 description 3
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 229940124091 Keratolytic Drugs 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000012641 Pigmentation disease Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 206010000349 Acanthosis Diseases 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019345 Heat stroke Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010039203 Road traffic accident Diseases 0.000 description 1
- 208000007180 Sunstroke Diseases 0.000 description 1
- 206010043268 Tension Diseases 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000004299 exfoliation Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000002395 mineralocorticoid Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 208000017983 photosensitivity disease Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 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
- A61K31/16—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
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A pharmaceutical composition for the treatment of vitiligo, comprises a mixture of urea, salicyclic acid, retinoic acid, anhydrous lanolin and triamcinolone acetonide, in an oil-in-water emulsion.
Description
SPECIFICATION
Improvements in or Relating to a Pharmaceutical
Composition
This invention relates to a pharmaceutical composition and more particularly a composition for use in the treatment of vitiligo, a disorder in which normal skin pigmentation is gradually lost, causing marks to appear. The diversity of the marks and their localization make it difficult to determine where the depigmentation started, the casual agents being difficult to determine.
The riskfactors likely to lead to vitiligo include stress, depressive states, anxiety, pregnancy, traumatic conditions, traffic accidents, sunstroke and nerves.
There are two theories about the appearance of vitiligo. According to the first theory, which is immunological, vitiligo can be considered as an autoimmune disorder-i.e. the individual reacts to nervous tension by producing antibodies which attack and destroy the melanogentic cells.
According to the second theory, conditions of severe nervous and emotional tension cause the nervous system to produce a substance which is so far unidentified and which poisons and kills the pigment-producing cells.
Although both of these theories are, of course, reasonable, it can be stated that there must be a breakdown and subsequent destruction of the enzyme synthesizing melanin in the liver.
The first agents known in the world to treat vitiligo were the psoralens, which have a catalytic action on pigmentation. However, the treatments using psoralens are very long and have serious psychic and organic secondary effects besides causing severe photosensitizations, interolerances and hepatotoxicity, and so they are not ideal.
Corticoid betametasone valerate is at present being used in small treatment zones because of its convenience of application without excessive solar exposure. It is used in infiltrations or topically at a strength of 0.2% in flexible collodion.
Hydroquinone monobenzylester has also been used as a treatment agent and so has a placenta extract which provides a rapid curing on the trunk and head and slow curing on hands and feet.
The effectiveness of dermatotherapy depends, of course, not only on the active substance employed but also on the excipient used.
Dermatopharmaceutica I excipients have two functions-having themselves a therapeutic effect and conveying active substances. The absorption of medicaments through the skin is very important since it is known from the structure of the skin that it is a secretion organ. The various layers of skin structure have different extents of transepidermic permeability from the inside to the outside and vice versa. A substance absorbed in the skin can remain in the intercellular spaces or pass through the cellular membrane and go from cell to cell.
Percutaneous absorption is a further possibility enabling the substance to pass through sweat glands, sebaceous glands and hair follicles.
The factors which can prevent an active agent penetrating human skin satisfactorily can be summarized as follows:
The effective impermeability of the surface of the skin and its covering of a fatty layer and a horny layer;
The effective impermeability layer of vital cells of the epidermis;
The inability of the active substances to pass through the skin;
The effective impermeability walls of the lymphatic and blood vessels;
An unsuitable excipient;
Insolubility of the active substance, and
A negative charge with H+ ions on the outside of the skin and OH- ions on the inside.
There is therefore a need in dermatotherapy for an appropriate excipient enabling the active substance to penetrate the skin, assisted by an extension of the time that the excipient remains adhered to the skin and a reduction of the factors which prevent the active agent penetrating the skin, with an increase in cell permeability.
Penetration depends upon the viscosity of the excipient and upon skin temperature. Adhesion between the medicament and the excipient is also an important factor.
The effectiveness of penetration can be expressed:
Q=(2 a D a3 t)112 where Q is the quantity of active substance evolved and which penetrates the skin, a is the thermodynamic activity of the active substance (concentration); a3 is the thermodynamic activity of the active substance; D is a diffusion constant of the active substance in the external phase; and t is the duration of the effect.
The kinds of vehicle used in dermatology include those acting as aqueous mixtures such as water, agitatable lotions and gels of hydrophilic colloids, those acting as oils, such as water-immiscible and water-miscible oils, 01w (oil-in-water) emulsions,
W/O (water-in-oil) emulsions pastes and colloids, those acting as powders, such hydrophilic powders and hydrophobic powders; and those acting as organic solvents such as water-miscible and waterimmiscible solvents.
Ointments can be classified by the composition of their bases; for example, there are oil-based ointments, absorption-based ointments, emulsionbased ointments and water-soluble-based ointment.
The rate of absorption of a drug in an aqueous phase is proportional to its concentration in the aqueous phase in contact with the membrane, and the rate at which a drug is absorbed by lipoid diffusion depends upon the partition coefficient between the aqueous phase and the oil phase of the membrane.
The molecular structure of drugs also affects their absorption; for instance, groups which are acid or basic or simultaneously both and which can be ionized in an aqueous solution result in only the non-ionized molecules being lipsoluble, while the possibility of absorption of these drugs through the lipoid membrane depends upon the non-ionized portion of molecuie which in turn depends upon the pH of the aqueous solution.
The non-ionized portion of molecule present in the aqueous phase at a given pH can be calculated from the extent of ionization of the compound as expressed by its ionization constant pKa.
When the pKa of a drug is equal to the pH of the aqueous phase on the surface of the lipoid membrane, the number of ionized molecules is the same as the number of non-ionized molecules.
In short, to produce a drug readily absorbable through the keratinized epidermis, an 01w emulsion ointment which will penetrate the cutaneous barrier satisfactorily must be used.
According to one aspect of this invention there is provided pharmaceutical composition for the treatment of vitiligo, comprising a mixture of urea, salicylic acid, retinoic acid, anhydrous lanolin, triamcinolone acetonide in an oil-in-water emulsion.
Preferably the composition comprises approximatelyfrom 1 to 10% by weight of salicylic acid, approximately 0.025 to 0.3% by weight of retinoic acid, and approximately 0.0 to 5.2% by weight of triamcinolone acetonide, and approximately 1 to 10% by weight anhydrous
lanolin.
Preferably the emulsion comprises an emulsifier
consisting of a mixture of liquid PCL, solid PCL,
beeswax, paraffin esters and ethoxylated fatty
alcohols.
The composition may additionally comprise water.
According to another aspect of this invention there is provided a process for the preparation of a composition forthetreatment of vitiligo, said process comprising the steps of heating to melting point a self-emulsifiable emulsifier consisting of a mixture of liquid PCL, solid PCL, beeswax, paraffin esters and ethoxylated fatty alcohols, together with anhydrous lanolin and propylene glycol, with agitation, mixing together urea, salicylic acid, retinoic acid and triamcinolone acetonide and adding the mixture to the melted emulsion, with agitation, in the presence of water.
The invention also relates to the use of a pharmaceutical composition in accordance with the invention in the treatment of vitiligo.
According to a further aspect of this invention there is provided, in the treatment, vitiligo, the step of applying, to the skin of a patient, a pharmaceutical composition in accordance with the invention.
The invention also relates to the use of a mixture of urea, salicylic acid, retinoic acid, and triamcinolone acetonide in the manufacture of a pharmaceutical for the treatment of vitiligo.
In order that the invention may be more readily understood, the invention will now be described, by way of example.
The preferred embodiment of the present invention comprises a topical cream for the treatment of vitiligo, the cream having, as compared with the prior art, the advantages are non-toxicity, convenience of application, absence of secondary effects, reduction of allergy risks, a shorter treatment time and quicker results.
The cream comprises a mixture of urea, salicylic acid, retinoic acid, anhydrous lanolin and triamcinolone acetonide, the above active ingredients being present in an excipientformed from an oil in water emulsion.
One example of a pharmaceutical preparation in accordance with the invention may be prepared utilising the steps set out below.
Initially a self-emulsifiable or neo PCL is heated to its melting point, with an hydros lanolin and propylene glycol. The mixture is agitated to form an excipient incorporating lanolin.
Separately urea, salicylic acid and retinoic acid are mixed with triamcinolone acetonide. The mixture is added to the excipient produced in the initial step, and distilled water may also be added. The result is a topical cream.
Preferably anhydrous lanolin is used in such a quantity as to form from 1 to 10% by weight of the topical cream prepared in the initial step, and in the mixture it is preferred that various components are used in the foliowing quantities, by weight, of the cream.
Urea 340% Salicylic acid 110% Retinoic acid 0.0250.3% Triamcinolone acetonide 0.0252% Neo PCL is a self emulsifiable mixture in the form of a white odourless composition, and acts as a nonionic absorption base. This material can be used in both acid and alkaline preparations and is thus suitable for the ready preparation of an oil-in-water emulsion cream. Neo PCL consists of liquid PCL, solid PCL, beeswax, parafine esters and ethoxilated fatty alcohols.
It is believed that the urea present in the composition of the invention acts as a diuretic and acts as a keratolytic substance which dissolves the keratin in the skin and increases the permeability of the horny layer of the skin.
It is believed that the salicylic acid has an antiseptic, anti-neuralgic, anti-rheumatic, disinfecting, keratolytic and exfoliative action when applied to the skin.
It is believed that retinoic acid applied topically produces a slight antiflammatory reaction thickening the skin (acanthosis) and a local intercellular edema with separation of the skin cells.
The horny layer is thus softened and exfoliation occurs. Retinoic acid also, it is believed, has a keratolytic action and also it facilitates rapid solution of the comedo characteristics of acne and inhibits the formation of further comedos.
Anhydrous lanolin is used as a vehicle, and it is believed that this material facilitates the absorption of active ingredients, and it also has emolient and emulsifying properties, lubricating the skin and muceous membranes. It does not turn rancid and so does not irritate the skin or mucosae. It is completely asceptic, and inhibits the growth of micro-organisms.
Triamcinolone acetonide has, it is believed, twice the antiallergic effect of prednisone and, unlike all the steroid hormones, is diuretic. It has secondary effects such as anorexia, cephalalgia and muscular weakness. It produces a mineral-corticoid action used in nephritic edemas. It produces a protein breakdown effect, increases the secretion of sweat and sebum and increase gluconeogenesis.
Claims (13)
1. A pharmaceutical composition for the treatment of vitiligo, comprising a mixture of urea, salicylic acid, retinoic acid, anhydrous lanolin, triamcinolone acetonide in an oil-in-water emulsion.
2. A composition according to claim 1 comprising approximately 3 to 40% by weight of urea, approximatelyfrom 1 to 10% byweightofsalicylic acid, approximately 0.025 to 0.3% by weight of retinoic acid, and approximately 0.0 to 5.2% by weight of triamcinolone acetonide, and approximately 1 to 10% by weight anhydrous lanolin.
3. A composition according to any one of the preceding claims wherein the emulsion comprises an emulsifier consisting of a mixture of liquid PCL, solid PCL, beeswax, paraffin esters and ethoxylated fatty alcohols.
4. A composition according to any one of the preceding claims additionally comprising water.
5. A process for the preparation of a composition for the treatment of vitiligo, said process comprising the steps of heating to melting point a selfemulsifiable emulsifier consisting of a mixture of liquid PCL, solid PCL, beeswax, paraffin esters and ethoxylated fatty alcohols, together with anhydrous lanolin and propylene glycol, with agitation, mixing together urea, salicylic acid, retinoic acid and triamcinolone acetonide and adding the mixture to the melted emulsion, with agitation, in the presence of water.
6. A process according to claim 5 wherein the anhydrous lanolin is used in the quantity of from 1 to 10% by weight.
7. A process according to claim 5 or 6 wherein the urea is used in a quantity of from 3 to 40%, the salicylic acid is used in a quantity of from 1 to 10%, the retinoic acid is used in a quantity of from 0.025 to 0.3% and the triamcinolone acetonide is used in a quantity of from 0.025 to 2% by weight.
8. The use of a pharmaceutical composition according to any one of claims 1 to 4 in the treatment of vitiligo.
9. In the treatment of vitiligo the step of applying, to the skin of a patient, a pharmaceutical composition according to any one of claims 1 to 4.
10. The use of a mixture of urea, salicylic acid, retinoic acid, and triamcinolone acetonide in the manufacture of a pharmaceutical for the treatment of vitiligo.
11. A pharmaceutical composition substantially as herein described.
12. A process for the preparation of a pharmaceutical composition substantially as herein described.
13. Any novel feature or combination of features disclosed herein.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES553334A ES8706027A1 (en) | 1986-03-24 | 1986-03-24 | Topical pharmaceutical compositions for treating vitiligo |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8628373D0 GB8628373D0 (en) | 1986-12-31 |
| GB2188233A true GB2188233A (en) | 1987-09-30 |
| GB2188233B GB2188233B (en) | 1990-07-18 |
Family
ID=8491041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8628373A Expired - Lifetime GB2188233B (en) | 1986-03-24 | 1986-11-27 | Topical pharmaceutical compositions for treating vitiligo. |
Country Status (2)
| Country | Link |
|---|---|
| ES (1) | ES8706027A1 (en) |
| GB (1) | GB2188233B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4119170A1 (en) * | 1991-06-11 | 1992-12-17 | Miltner Geb Herber Erika Dr | Synergistic compsn. for treating neuro-dermatitis - comprises triamcinolone acetonide, salicylic acid or its acetyl deriv., and coal tar extract |
| FR2718022A1 (en) * | 1994-04-01 | 1995-10-06 | Roussel Uclaf | Cosmetic or dermatological compositions and their preparation |
| CN1042896C (en) * | 1993-12-06 | 1999-04-14 | 广东医学院 | External compound corticoid preparation |
| WO2006088310A1 (en) * | 2005-02-15 | 2006-08-24 | Stiefel Laboratories Korea | A pharmaceutical composition comprising retinoid for prevention and treatment of vitiligo |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2047456B1 (en) * | 1992-07-31 | 1994-10-01 | Herrando Carlos Postigo | COMPOSITION TO OBTAIN A COSMETIC PRODUCT AND SIMILAR PRODUCTS. |
| ES2083333B1 (en) * | 1994-09-22 | 1997-01-16 | Corral Begona Gozalo | CREAM FOR THE TREATMENT OF PSORIASIS. |
| ES2119726B1 (en) * | 1997-03-20 | 1999-04-01 | Reolid Manuel Sanchez | COMPOSITION OF A PRODUCT FOR BODY APPLICATION. |
| ES2156765B1 (en) * | 1999-11-05 | 2002-02-01 | Herrando Carlos Postigo | COMPOSITION OF A PRODUCT APPLICABLE TO SKIN. |
| ES2607630B2 (en) * | 2016-03-09 | 2017-09-25 | Paz LOPEZ PITA | Topical cream of clobetasol-17 propionate, urea and marigold oil and manufacturing procedure |
-
1986
- 1986-03-24 ES ES553334A patent/ES8706027A1/en not_active Expired
- 1986-11-27 GB GB8628373A patent/GB2188233B/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| MARTINDALE, THE EXTRA PHARMACOPOEIA, 1982 (28TH EDITION), SALICYLIC ACID, PP.277-278, TRIAMCINOLONE ACETONIDE}, P.484 P.459, TRETINOIN (RETINOIC ACID)P.508, UREA PP.616-617, LANOLIN, P.1072, * |
| THE MERCK MANUAL OF DIAGNOSIS AND THERAPY, 1982 (14TH EDITION)P.2068 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4119170A1 (en) * | 1991-06-11 | 1992-12-17 | Miltner Geb Herber Erika Dr | Synergistic compsn. for treating neuro-dermatitis - comprises triamcinolone acetonide, salicylic acid or its acetyl deriv., and coal tar extract |
| DE4119170C2 (en) * | 1991-06-11 | 2002-04-25 | Geb Herber Miltner | Remedies for atopic dermatitis |
| CN1042896C (en) * | 1993-12-06 | 1999-04-14 | 广东医学院 | External compound corticoid preparation |
| FR2718022A1 (en) * | 1994-04-01 | 1995-10-06 | Roussel Uclaf | Cosmetic or dermatological compositions and their preparation |
| EP0676194A2 (en) * | 1994-04-01 | 1995-10-11 | Roussel Uclaf | Cosmetic or dermatological compositions comprising an alpha-hydroxy acid, salicylic acid and a retinoid |
| EP0676194A3 (en) * | 1994-04-01 | 1997-04-23 | Roussel Uclaf | Cosmetic or dermatological compositions comprising an alpha-hydroxy acid, salicylic acid and a retinoid. |
| US5652266A (en) * | 1994-04-01 | 1997-07-29 | The Boots Company Plc | Cosmetic or dermatological compositions |
| WO2006088310A1 (en) * | 2005-02-15 | 2006-08-24 | Stiefel Laboratories Korea | A pharmaceutical composition comprising retinoid for prevention and treatment of vitiligo |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8628373D0 (en) | 1986-12-31 |
| ES553334A0 (en) | 1987-05-16 |
| GB2188233B (en) | 1990-07-18 |
| ES8706027A1 (en) | 1987-05-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19951127 |