CA2067770A1 - Composition for the topical treatment of psoriasis - Google Patents
Composition for the topical treatment of psoriasisInfo
- Publication number
- CA2067770A1 CA2067770A1 CA002067770A CA2067770A CA2067770A1 CA 2067770 A1 CA2067770 A1 CA 2067770A1 CA 002067770 A CA002067770 A CA 002067770A CA 2067770 A CA2067770 A CA 2067770A CA 2067770 A1 CA2067770 A1 CA 2067770A1
- Authority
- CA
- Canada
- Prior art keywords
- corn
- composition
- weight
- acid
- gamma
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/47—Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
Abstract
The invention relates to a pharmaceutical composition suitable for the topical treatment of psoriasis comprising an aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob and gamma-linolic acid as active ingredient admixed with one or more solid and/or liquid carriers and/or other additives.
Description
W092/03142 2 ~ S ~ 7 ~ ~ PCT/HU9l/00038 ' ~ - 1 Composition for the topical ~reatment of psoriasis The invention relates to compositions suitable ~or the topical treatment of psoriasis as well as to the process for the preparation of said compositions.
The compositions according to the invention contain the extract of different parts of maize plant (Zea mays) together with gamma-linolic acid as active ingredient.
The different clinical and laboratory investigations have clearly shown that the psoriasis is qenerally not induced by a single cause, but by the complex resultant of different procedures being with one another in casual relation.
The incidence of the psoriasis is different but it occurs all over the world, men and women can equally suffer from it and the number of the patients amounts to 0.3-4.8% of the entire population. The illness can occur at any age, but most frequently people of the age from 10 to 30 years get ill.
The psoriasis belongs to the group of papulosquamous diseases which can be characteri~ed by silverous squamae, considerable desquamation and anarchic cell division (karyokinesis). At the beginniny papules having a diameter of 3-5 mm and covered with parakeratosis appear which can gradually join and/or increase and so can form plaques having a diameter of several cm. Cell kinetic investigations prove that the reproduction of the epidermic cells takes place very quickly. In normal case the time of a cell cycle is about 311 hours, whereas the same i5 shortened to 36 hours in case of psoriasis patients. The clinical picture shows generally a progression at the edges and a centrai improvement. Most characteristic is the occurrenc:e on the elbow, on the knee and on the scalp.
Psoriasis is the inherited deficiency of the . ..
W092/03]42 PCT/HU91/00038 2 ~ 7~ 2 -epidermic regulation as well as the disorder of the haemostase owing to which one has to face with both local and systemic effect in connection with the various clinical forms of psoriasis.
The function of inheritance in the formation of psoriasis nowadays is generally acknowledged and it is believed to be in connection with the Cw6 psoriatic gene. Various authors are of different opinion as to the mode and process of the inheritance but in general the so called polygenic~ multifactorial inheritance procedure is accepted.
The fact of the inheritability can be supported e.g.
by the following observations:
- the mass incidence on certain geographical territories - the incidence within families is more frequent, - it is also proved by genetic investigations.
The local disorder of the relevant biochemical regulation belongs to the complax patogenetic factors as well. The injury of the cAMP system can cause disorder in the epidermic autoregulation, so e.g. upon administration of lithium (which decreases the cAMP
level) the psoriasis declines, however the inhibitors of enzymes (e.g. phosphordiesterase-PDE) decomposing the 2_ cAMP system, (e.g. Theophillin) influence advantageously the disease.
The immune system, the arachidonic acid system as well as the polyamine metabolism and the various proteinases may also have a significant function in the formation of the disease as these systems differently influencle the metabolism of the cyclic nucleotides.
Particularly discussed is the function of the arachidonic acid system as the drugs enhancing the level of free arachidonic acid (e.g. the non-steroid antiphlogis~ics) make the psoriasis worse.
.
WO92/03142 7~ PCT/HU91/00038 ,. . .
It is also proved by several clinical and biological tests that in ~ase of psoriasis the level of the free arachidonic acid and their derivatives (12-hydroxy-eicosatetraenoic acid, 12-ETE) is increased in the epidermic layer of the skin.
The characteristic types of psoriasis are as ~ollows:
l) Psoriasis guttata: disseminated phenomena having a diameter of 0.5-1.5 cm are present on the whole skin.
2) Plaque form: the appearance is similar to the previously mentioned type but the phenomena are prolonged and accompanied with inflammation.
The compositions according to the invention contain the extract of different parts of maize plant (Zea mays) together with gamma-linolic acid as active ingredient.
The different clinical and laboratory investigations have clearly shown that the psoriasis is qenerally not induced by a single cause, but by the complex resultant of different procedures being with one another in casual relation.
The incidence of the psoriasis is different but it occurs all over the world, men and women can equally suffer from it and the number of the patients amounts to 0.3-4.8% of the entire population. The illness can occur at any age, but most frequently people of the age from 10 to 30 years get ill.
The psoriasis belongs to the group of papulosquamous diseases which can be characteri~ed by silverous squamae, considerable desquamation and anarchic cell division (karyokinesis). At the beginniny papules having a diameter of 3-5 mm and covered with parakeratosis appear which can gradually join and/or increase and so can form plaques having a diameter of several cm. Cell kinetic investigations prove that the reproduction of the epidermic cells takes place very quickly. In normal case the time of a cell cycle is about 311 hours, whereas the same i5 shortened to 36 hours in case of psoriasis patients. The clinical picture shows generally a progression at the edges and a centrai improvement. Most characteristic is the occurrenc:e on the elbow, on the knee and on the scalp.
Psoriasis is the inherited deficiency of the . ..
W092/03]42 PCT/HU91/00038 2 ~ 7~ 2 -epidermic regulation as well as the disorder of the haemostase owing to which one has to face with both local and systemic effect in connection with the various clinical forms of psoriasis.
The function of inheritance in the formation of psoriasis nowadays is generally acknowledged and it is believed to be in connection with the Cw6 psoriatic gene. Various authors are of different opinion as to the mode and process of the inheritance but in general the so called polygenic~ multifactorial inheritance procedure is accepted.
The fact of the inheritability can be supported e.g.
by the following observations:
- the mass incidence on certain geographical territories - the incidence within families is more frequent, - it is also proved by genetic investigations.
The local disorder of the relevant biochemical regulation belongs to the complax patogenetic factors as well. The injury of the cAMP system can cause disorder in the epidermic autoregulation, so e.g. upon administration of lithium (which decreases the cAMP
level) the psoriasis declines, however the inhibitors of enzymes (e.g. phosphordiesterase-PDE) decomposing the 2_ cAMP system, (e.g. Theophillin) influence advantageously the disease.
The immune system, the arachidonic acid system as well as the polyamine metabolism and the various proteinases may also have a significant function in the formation of the disease as these systems differently influencle the metabolism of the cyclic nucleotides.
Particularly discussed is the function of the arachidonic acid system as the drugs enhancing the level of free arachidonic acid (e.g. the non-steroid antiphlogis~ics) make the psoriasis worse.
.
WO92/03142 7~ PCT/HU91/00038 ,. . .
It is also proved by several clinical and biological tests that in ~ase of psoriasis the level of the free arachidonic acid and their derivatives (12-hydroxy-eicosatetraenoic acid, 12-ETE) is increased in the epidermic layer of the skin.
The characteristic types of psoriasis are as ~ollows:
l) Psoriasis guttata: disseminated phenomena having a diameter of 0.5-1.5 cm are present on the whole skin.
2) Plaque form: the appearance is similar to the previously mentioned type but the phenomena are prolonged and accompanied with inflammation.
3) Palmar-plantar psoriasis: a less inflamed scaly, thick~ned alteration which can be rent at the edges and sterile blisters may occur.
4) Scalp psoriasis: moderately inflamed, strongly scaly, generally itching, circumscribed - phenomena, possibly covering the whole scalp, without any loss of hair.
The complicated forms of psoriasis are as follows:
1) Erythroderma psoriasis: inflammatory and scaly symptoms appear on the whole skin, the plaques and papules are totally joined.
2) Psoriasis pustulosa: is generally localiæed to the palm and planta, sometimes spreads on the -whole skin surface. It is very severe, fatal disease.
3) Psoriasis arthropathy: besides the charac-t~ristic symptoms o~ the skin, arthritis develops too, mainly (and initially) on one of the hands.
According to our present knowledge all types of psoriasis are treated s~mptomatically. The local .
': .
W092~03142 PCT/HU91/00038 ~ 4 treatment has different aims: a) supression of the inflammatory reactions; b~ removal of the accumulated squamae; c) decrease of the ephithelial cell activity;
and d) prevention of the superinfection of the injured skin surface.
In uncomplicated cases thPse requirements can be satisfied partly with local treatment and in complicated cases partly with local treatment and partly with internal treatment carried out simultaneously.
According to the state of art the following materials have been suggested so far for local treatment.
Coal-tar and tar of vegetable origin have been best known and widely used active ingredient which were applied in a concentration of 3-lO~ in form of ointments, painting and bath compositions. Nowadays however the use of these materials is avoided due to their carcinogenic side effects.
The phototherapy has also been known for a long time as it has been observed that the sunshine is very useful in the treatment of most types of psoriasis. This therapy can be used alone or in combination with photosensitizing drugs.
The different bathes represent a very important additional treatment for all types of psoriasis diseases. Depending on the composition of the medicinal water partly the removal of the squamae partly a decrease of the inflammatory symptoms can be achieved. ~;
Formerly dithranol, the synthetic version of crysarobin of plant origin, was also used for the treatment of psoriasis but due to its definite irritating side effect and pigmenting properties it is no longer applied. -The-most efficient,antiphlogistics and proliferakion inhibiting materials are the corticosteroids (e.g~
.
.
WO92/03142 2~67 ~f7~ PCT/HU91/00038 i . .
Dermovate=21-chloro-9-flUoro-llbetal7-dihydroxy-16beta-methylpregna-l~4-diene-3l2o-dioni Diproderm=9-fluoro-llbeta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dion-17,21-dipropionate; Diploren) which can S be used for the treatment of all types of psoriasis.
These drugs have symptomatic effect and relatively shortly after interrupting the treatment recidivation takes place, their long-lasting use, however, can result in atrophy of the connective tissues, and certain habituation to it can also be observed. Therefore for long-lasting treatment only steroides showing less side-effects (e.g. Hydrocortison, Prednisolon) are suitable.
Treatment with systemic corticosteroids can be taken into consideration only in complicated cases, but only for short period. -For the time being the most frequently used agentsfor systemic treatments - exclusively in severe cases -are the aromatic derivatives of vitamine A, the so called retinoids (e.g. Tigason=etretinate). These drugs, however, can only be applied very carefully as they have serious side effects (e.g. increase of the serum lipid level, hypertension, teratogenesis).
According to the aforementioned the treatment of psoriasis has not been solved sufficiently yet. All the known compositions have side effects, and the fact that only a few topical compositions are known proves that good results can be achieved only with the oral composit:ions.
The object of our invention was to ensure a topical composition for the treatment of psoriasis.
Further object of our invention was to develop a composition without any harmful side e~fect (e 9 g.
carcinogenic, teratogenic, bone marrow damaging, adrenal disfunction producing effect, etc.) during the use of which no pigmentation, dehydratation, atrophy, super~
.:
, W092/03l42 PCT/HU9l/00038 2~ 7~ - 6 -infection on the injured skin surface occur and its application is not limited by interaction with other drugs.
Surprisingly it has been found that a composition comprising the aqueous and/or pharmacologically accept-able organic solvent, preferably ethanolic extract of the young crop and/or beard (silk) and/or nodulous stalk and/or cob of maize plant and gamma-linolic acid can be used for the treatment of psoriasis without any side effect.
It is known from HUP No. 195,915 (USP No. 4,950,481) that the aqueous and/or ethanolic extract of the young crop and/or bread and/or nodulous stalk and/or cob of maize possesses skin sedative and skin regenerative effect.
The aqueous and/or ethanolic extract comprises the following active ingredients:
- carbohydrates (mono- and oligosacharides, poly-sacharides), - fats, oils, fatty acids (phospholipides, glycolipides, galactolipides), - proteins, amino acids, - phenolic materials (~lavonoides, coumarines, phenyltropanes and the phenolic materials), - terpenes (sesquiterpenes, triterpenes, te~ra-terpenes), -- vitamins, volatile oils.
Out of the above components first of all the poly-sacharides and flavonoides possess antiphlogistic effect.
The phospholipids are emulsifiers and are frequently used in cosmetic compositions as additives.
The gamma-linolic acid is an essential amino acid and being "body-friend" (histotropic), has no harm~ul - side effect.
The O~nothera oil containing gamma-linolic acid has '- ' - ' :
2~7~7~
been successfully used mainly for the treatment of different complicated and uncomplicated cardiovascular diseases. It was able to decrease the thrombocyte aggregation, to normalize the lipid levels, however in the popular therapy it has been also used as oral antispasmodic and antiphlogistic agent.
Surprisingly the corn extract used so far in cosmetic compositions and having mild antiphlogistic effect, together with gamma-linolic acid is efficient in lo the treatment of uncomplicated psoriasis diseases and after the treatment the patients became symptomless. As the composition contains only natural active ingredients it has no side effect. The active ingredients of the composition according to the invention separately are not able to ensure the desired effect, they are effective against psoriasis only in case of their common use.
Accordingly the invention relates to pharmaceutical compositions suitable for the topical treatment of psoriasis which comprises an aqueous and/or pharma-ceutically acceptable organic solvent, preferablyethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob together with gamma-linolic acid as active ingredient admixed -with one or more solid and/or liquid carrier(s) and/or additives.
Concentration of the active ingredient is preferably lS-75~ by weight.
A further object of the invention is a process for the preparation of a pharmaceutical composition suitable ~or the topical treatment of psoriasis in which the aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn~crop - and/or corn-beard and/or nodulous corn-stalk and /or corn-cob and gamma-linolic acid as active ingredient are admixed with one or more soli~ and/or liquid carrier(s) W092/03]42 PCT/HU91/00038 2~
and/or additive(s) and the mixture thus obtained is formed into cream, emulsion or solution suitable for topical use.
The corn extract used in the composition according to the invention can be prepared in a manner known per se, eOg. the method described in US P No. 4,590,481 can be used.
The extract can be prepared e.g. by extracting the optionally dried plant pieces with a 2-30-fold amount -calculated for the dry mass of the plant - of water or aqueous solution of a cosmetically acceptable organic solvent at a temperature between 15 and 95C and separating the solid phase ~plant pieces) from the liquid phase.
Alternatively, the extract can also be obtained as follows: plant pieces are crushed and steeped in the above mentioned solvents. The time of steeping can vary within a wide range, preferably between 5 and 48 hours.
On industrial scale the extraction is preferred as it can be carried out within a shorter time, (e.g. 30-60 minutes).
After the extraction or steeping the product obtained may be sterilized by heating it one or more times, preferably three-times to 80C and heating it at this temperature for a short period.
For the extraction generally water or the aqueous solution of a water-miscible pharmaceutically acceptable organic solvent, e.g. ethanol is used.
The pharmaceutical sompositions according to the invention contain the active inyredient and one or more pharmaceutically acceptable solid and/or liguid carrier~s) and/or additives.
The compositions according to the invention may contain as solid carrier for example talc, zinc oxide, bentonite, Xaolin, colloidal silica, titanium-dioxide;
W092/03142 2~ 77~ PCT/HU91/00038 _ g _ corn-starch, potato starch. Solid emulsifying agents, e.g. fats, fatty alcohols, fatty acid, fatty acid esters, waxes can also be used as solid carriers.
The compositions according to the invention may contain as liquid carrierc~ one or more pharmaceutically acceptable, to the skin non-irritative liquid solvent(s), e.g. water, ethanol or animal or vegetable oil.
The compositions according to the invention may contain as carrier and emulsifier respectively in the cosmetic industry generally used fats, oils, waxes, fatty acids and esters and glycerides thereof obtained with higher alcohols.
The fatty acids m~y be straight or branched having 12-18 carbon atoms, may be saturated or unsaturated and may also be substituted with one or more hydroxy group(s).
Suitable fatty acids are selected from the group ` ;
consis~ing of undecenoic acid, laurylic acid, caprylic acid, myristic acid, palmitic acid, isopalmitic acid, stearic acid, isostearic acid, hydroxy stearic acid, oleic acid, hydroxy-oleic acid, behenic acid, lanolinic acid, arachidonic acid, octyldecanoic acid, pentadecanoic acid or the mixture thereo~.
Suitable fatty acid-esters are selected from the group consisting of isopropyl myristate, butyl myristate, octyldodecyl myristate, isocetyl myristate, cetyl myristate, ethyl palmitate, isopropyl palmitate, hexadecyl stearate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, cetyl ricinoleate, propylenglycol dipelargonate, 2-ethylhexyl isononate, hexyl laurate, 2-ethylhexyl stèarate, ~atty alcohol lactate having 12-16 carbon atoms, triglycerides of octanoic and dekanoic acids salicylate and the mixture thereof.
: :
.~ ..
, ;. .:
, ~'.
, 2~7~ o -As fatty alcohol e.g. alkohols having 14-22 carbon atoms, e.g. behenyl alcohol, myristyl alcohol, arachidyl alcohol, steary:L alcohol, isostearil alcohol, cetyl alcohol, cetyl-stearyl alcohol, isoce'~l alcohol, oleyl alcohol, lauryl alcohol may be mentioned.
As liquid carrier various oils or oil mixtures applied generally in the cosmetic industry can also be used. The oils act as stabilizing agent in the emulsions and ensure a cosmetically suitable viscosity for the emulsion.
Suitable oils are selected from the group consisting of aliphatic hydrocarbons (e.g. liquid paraffine, vaseline, ceresine etc), vegetable oils and fats (e.g.
olive oil, almond oil, wheat-germ oil, corn-germ oil, cotton-seed oil, grape-stone oil, jojoba oil, avocado oil, castor oil, palm oil, cocoa butter etc.), animal fats and oils (e.g. cod-liver oil, blubber oil, butyrine, etc.) The compositions according to the inven~ion may contain as other additives e.g. one or more hygroscopic material(s), solubilizing and stabilizing agent, -preservative, disinfectant, skin sedating, skin protecting, epithelium regenerating, skin re-fatting, light-protecting and aromatizing materials, vitamins, etc.
As hygroscopic materials e.g. glycerol, sorbitol, propylene glycol may be used.
As solubilizing material e.g. butyl-hydroxy-anisole, butyl-hydroxy-toluene, ethylene-diamine-tetraacetic acid, nor-dihydroguaiaretic acid may be used.
A preservative e.g. methyl parabene, p-hydroxy-benzoic acid and esters thereof, chloromethyl-iso-thiazoline, methyl-isothiazoline, phenoxetole, hexetidine, chlorohexidine-gluconate, imidazolinyl urea can be used. I~ desired formaldehide and similar other W O 92/03142 ~ 7~ PC~rtH U91/00038 , .
preservatives may also be used.As tonic or disinfectants e.g. menthol, camphor, lactic acid, citric acid, ethanol can be used.
As epithelium regenerating material e.g.
allanthoine, panthenol, calcium pantothenate can be used.
As skin sedating material e.g. chamomile extract, azulenole, bisabolole can be used.
As skin protecting and re-fatting matexial e.g.cholesterol, propane-3-carboxymethyl-betaine, 1--(alkylamino)-3-(dimethylamino)-propane-3-N-oxide, propane-3-(carboxymethyl)-betaine, alkyl-dimethylamin-oxide, mono- and di-ethanolamide of cocoa acid can be used.
As light protecting (sunscreening) material e.g.
octyl-dimethyl-PABA, 2-hydroxy-4-methoxy-benzophenone, 2-(ethyl-hexyl)-3-(4-methoxy-phenyl)-2-propenoate, 1-(4-methoxy-phenyl)-3-(4-tert-butyl-phenyl)-propane-1,3-dione, urocainic acid, esculine can be used.
As vitamin, e.g. A, B, Bl, C, E, F, H, P vitamin can be used.
~ s aromatizing material e.g. parfume oil can be used which ensures a pleasant and attractive smell for the composition.
The composition according to the invention can be formulated into different forms suitable for topical treatment, eOg. cream, ointment, emulsion, solution, tonic, gele, etc. can be prepared.
The creams and the ointments according to the invention contain 30-70~ by weight of corn extract and 0.05-3~ hy weight of gamma-linolic acid as active ingredient. ~, The emulsions according to the invention contain 15--30% by weight of corn extract and 0.05-3~ by weight of gamma-linolic acid as active ingredient.
~ 35 The solutions according to the invention contain .
. .
2~'S~7~7~ - 12 -preferably 30-50% by weight of corn extract and 0.05-3%
by weight of gamma-linolic acid as active ingredient.
The amount of water and aqueous solvent used in the compositions depends on the consistency of the desired s end product. The water used is preferably deionized water and the amount thereof is generally 27-75~ by weight calculated for the total amount of the composition. The cream and ointment compositions contain generally at least 20~ by weight but max. 60% by weight of water, the water content of the emulsions is prefera~ly 50-70% by weight and that of the solutions preferably 40-70~ by weight.
The following non-limiting Examples show the compositions of the invention.
The corn extracts used in Examples 1, 2 and 3 were prepared according to Example 1 o~ HU P No. 195,915 `~
(using water as extraction solvent), the corn extract used in Example 6 was prepared according to Example 6 of said patent specification (using ethanol as solvent) and the corn extract used in Examples 4, 5 and 7 were prepared according to Example 3 of the same patent specification.
The corn extracts used in Examples 1-5 were prepared from the crops, hypsophylls, cob, beard and nodulous stalk o~ the young corn plant, for the preparation of corn extracts used in Example 6 and 7 hypsophylls and crops of corn plant, and hypsophylls, cob and beard respectively, were used.
The products specified with trade marks contain the followiny compounds:
Hostacerin WO: fatty acid-polyglycerol ester (Hoechst AG, DE) Lanette N: mixture of sodium-cetyl-stearyl sulfate and cetyl-stearyl alcohol (Henkel, DE) BRIJ71: ethoxylated stearyl alcohol ~JCI, USA) W092/03142 2~777~ PCT/HU91/00038 BRIJ72l: ethoxylated stearyl alcohol (JCI, USA) Chremophor W07: hydrogenated castor oil (BASF, DE) Genagol AMS: detergent and surfactant (Hoechst, DE) Hoe S 3495: ethoxylated fatty acid-polyglycerol ester (Hoechst, DE) Examplo l Cream for day Composition: amounts (g) Corn extract 45.0 Gamma linolic acid O.lO
Cetyl alcohol 7.65 .
Stearin 2.35 Castor oil 4.00 Yaseline oil 6.00 Corn-germ oil 5.00 Na-lauryl sulfate l.00 Glycerol 5.00 Cholesterol l.00 Vitamin A 0.05 Vitamin E O.lO .
Preserving, aromatizing material 0.20 -Deionized water ad lO0.00 :i:
~5 Example 2 --~.
Night creau Composition: amounts (g) Corn extract 60.00 Gamma linolic acid 0.12 Hoctacerin WO lO.O0 Light vaseline 5.00 ;
Lanette N 2.00 :
Avocado oil lG.00 .
Vaseline oil 4.00 Wheat-germ oil 5.09 - , ':
' E~ample 2 continuad Composition: amounts (g) Cholesterol 3.00 Glycerol O.lO
Vitamin A 0.05 Vitamin E 0.05 Preserving, aromatizing material 0.02 Deionized water ad lO0.00 Example 3 Body lotion Composition: amounts (g~
Corn extract 40.00 Gamma-linolic acid O.lO
Cetyl alcohol l.50 Castor oil l.S0 Corn-germ oil 3.00 Vaseline oil l.00 BRIJ 72 2.50 BRIJ 721 l.60 Soorbitol 5Ooo Glycerol 6.00 - Vitamin A 0.05 ~ -Vitamin E 0.05 Preserving, aromatizing material 0.20 Deionized water ad lO0.00 Example 4 Emul3ion Composition: amounts (g) --Corn extrac_ 15.00 Gamma-linolic acid O.l5 Chremophor WO 7 6.00 Avocado oil 4.00 Corn-qerm oil 3.00 ~; .
, , ' W O 92/03]42 2~S777'~ PC~r/H U91/00038 Example 4 conti~ued Composition: amounts (g) Vaseline oil 14.00 Cetyl alcohol 1.00 Propyleneglycol 4.00 Vitamin A 0 05 Vitamin E ~.07 Preserving, aromatizing material 0.20 Deionized water 100.00 Example 5 Solution for medical tr~atment Composition: amounts (g) ~:
Corn extract 35 00 -Gamma-linolic acid 0.08 Izopropyl-alcohol 5.00 Menthol 0.03 Camphor 0.02 Sar~oxethene laurate 2.00 :
Propyleneglycol 10.00 Vitamin B1 0.10 ::
Preserving, aromatizing material 0.20 : .
Deionized water ad 100 ~a~ple 6 . :
~olution Composition: amounts (g) Corn extract 30.00 Gamma-linolic acid 0.10 Izopropyl-alcohol 5.00 -Ethanol 19.00 Menthol 0~05 Lactic acid 1.00 Sorboxethene-laurate 0.50 ..
Propylene glycol 10.00 - ' ' . - .:
2~77~ - 16 - ' Example 6 continued Composition: amounts (g) Preserving aromatizing material 0.20 Deionized water ad 100.00 Example 7 8hampoo Composition: amounts (g) Corn extract 75.00 Gamma-linolic acid 0.08 Na-lauryl sulfate 10.00 Genagol AMS 5.00 Hoe S 3495 1.00 Panthenol 2.00 Propane-3-carboxymethyl-betain5.00 Methyl-p-hydroxy-benzoate 0.20 Aromatizing material 0.50 Deionized water ad lOO.OO
The effect of the composition according to the invention were proved by the following clinical tests.
Experime~t 1 The composition according to Example 1 was tested on 11 female patients of the age of Z1 to 68 years and on lO male patients of the age of 33 to 73 years. The patients suffered from psoriasis for 12 years on an average. Tbe cream was applied to the injured skin surface 3 times a day and the treatment was continued for 3 wee~s. The results obtained are summarized in Table 1. The abbreviations used have the following meaning:
N- number of the patients suffering from the given type of psoriasis CI= considerable improvement WO92/03142 PCT/~U91t~0038 ~7~
SI= slight improvement D= deterioration Table 1 Type of psoriasis N CI SI D
Plaque disseminatio 11 7 1 3 ~rithroderma psoriaticum 2 Guttata disseminatio 2 10 Seborrhea typ. 1 1 - -Palmoplantaris typ. 4 4 Psoriasis localized to limbs 1 1 - -Total 21 15 3 3 It appears from the above Table that the condition of 71% of the patients improved considPrably, in case of 15~ a slight improvement and in case of 14%
deterioration was observed. Especially good results were obtained in connection with the seborrhoea type and palmoplantaris type psoriasis as well as in case of psoriasis localized to limbs.
Comparati~e experiment 2 For comparison, the composition according to Example 1 but containing 45.0 g wheat-germ oil instead of 45 g corn extract was tested on 10 male patients of the age of 32-70 years and on 10 female patients of the age of 20-65 years. The patients suffered from psoriasis 30 for 11 years on an average. The cream was applied to the - ;~
injured surface 3 times a day and the treatment was continued for 3 weeks. The results obtained are -~
summarized in Table 2. -. ~ :.
Table ~
";
2a?~777~ i -Type of psoriasis N CISI D
Plaque disseminatio 8 1 4 3 Erithroderma psoriaticum 2 Guttata disseminatio 2 5 Seborrhea typ. 3 Palmoplantaris typ.
Psoriasis localized to limos 4 1 1 2 Total 20 3 9 8 From the above Table it appears that the number of patients showing considerable improvement decreased (to 15%), the number of patients showing slight improvement increased (to 45~) and the amount of patients with deteriorated condition increased to 40~. Considerable improvement could be achieved only in case of one patient suffering from plaque disseminatio, seborrhoea type psoriasis and psoriasis localized to limbs, due to the skin sedative effect of the cream mostly slight improvement could only be achieved.
According to the aforementioned it can be established that the gamma-linolic acid without corn extract is not suitable for the treatment of psoriasis.
Comparative experiment 3 For further comparison the composition according to Exampl~ l but containing O.Ol g of wheat-germ oil instead of O.1 g gamma-linolic acid was tested on 13 male patients of the age of 28 to 60 years and on 7 female patients of the age of 22 to 67 years. The patîents suffered from psoriasis for 11 years on an average. The cream was applied to the injured skin surface 3 times a day. The treatment was continued for 3 weeks. The results obtained are summarized in Table 3.
. .
-WO92/03142 ~ 7 7 ~ PCT/HU9l/00038 !
Tahle 3 .
Type of psoriasis N CI SI D
Plaque disseminatio 10 3 4 3 5 Erithroderma psoriaticum 3 - 2 Guttata disseminatio 1 - -Seborrhea typ. 2 Palmoplantaris typ. 2 Psoriasis localized 10 to limbs 2 Total 20 3 9 8 From the above Table it appears that the number of patients showing considerable improvement decreased (to 15~), the number of patients showing slight improvement increased (to 45~) and deterioration was established in 40% of the patients. Considerable improvement could be achieved only in case of plaque dissemination, in other cases the slight improvement was proba~ly due to the :
mild antiphlogistic effect of the corn extract.
The above Table clearly shows that th~ anti-phlogistic effect of the corn extract alone is not able to decrease the occurrence of symptoms of different types of psoriasis, the composition containing no gamma--linolic acid possesses less activity than the composition according to Example 1.
~perime~t 4 The composition according to Example 6 was tested on 16 male patients aged from 3Q to 60 years and on 13 female patients of the age of 22 to 60 years. The patients suffered from scalp psoriasis, for 10 years on the average. The solution was applied 3 times a day and the treatment was continued for 3 weeks. The results obtained are summarized in Table 4.
- ':
.
Table 4 Strength of the Before After symptoms treatment Medium Nild Medium Mild Parakeratosis 9 20 5 o Infiltration 9 20 7 o Burning 3 20 2 0 Itching 7 20 5 3 The Table clearly shows that the solution according to Example 6 has eliminated the mild parakeratosis, infiltration, burning and itching in all the 20 patients. That means that in case of mild symptoms an efficiency of 100% can be achieved.
In case of medium parakeratosis and infiltration lOO~ efficiency was achieved in 4 and 2 patients respectively out of 9 patients, however in ease of medium burning the symptoms were totally eliminated in 1 . .
patient out of 3 patients.
Treatment of patents sufferin~ from extremely serious alteration was not carried out at all as according to clinical experiences such cases can be made symptomless - for a short period - only by systemic :.
treatment.
':
The complicated forms of psoriasis are as follows:
1) Erythroderma psoriasis: inflammatory and scaly symptoms appear on the whole skin, the plaques and papules are totally joined.
2) Psoriasis pustulosa: is generally localiæed to the palm and planta, sometimes spreads on the -whole skin surface. It is very severe, fatal disease.
3) Psoriasis arthropathy: besides the charac-t~ristic symptoms o~ the skin, arthritis develops too, mainly (and initially) on one of the hands.
According to our present knowledge all types of psoriasis are treated s~mptomatically. The local .
': .
W092~03142 PCT/HU91/00038 ~ 4 treatment has different aims: a) supression of the inflammatory reactions; b~ removal of the accumulated squamae; c) decrease of the ephithelial cell activity;
and d) prevention of the superinfection of the injured skin surface.
In uncomplicated cases thPse requirements can be satisfied partly with local treatment and in complicated cases partly with local treatment and partly with internal treatment carried out simultaneously.
According to the state of art the following materials have been suggested so far for local treatment.
Coal-tar and tar of vegetable origin have been best known and widely used active ingredient which were applied in a concentration of 3-lO~ in form of ointments, painting and bath compositions. Nowadays however the use of these materials is avoided due to their carcinogenic side effects.
The phototherapy has also been known for a long time as it has been observed that the sunshine is very useful in the treatment of most types of psoriasis. This therapy can be used alone or in combination with photosensitizing drugs.
The different bathes represent a very important additional treatment for all types of psoriasis diseases. Depending on the composition of the medicinal water partly the removal of the squamae partly a decrease of the inflammatory symptoms can be achieved. ~;
Formerly dithranol, the synthetic version of crysarobin of plant origin, was also used for the treatment of psoriasis but due to its definite irritating side effect and pigmenting properties it is no longer applied. -The-most efficient,antiphlogistics and proliferakion inhibiting materials are the corticosteroids (e.g~
.
.
WO92/03142 2~67 ~f7~ PCT/HU91/00038 i . .
Dermovate=21-chloro-9-flUoro-llbetal7-dihydroxy-16beta-methylpregna-l~4-diene-3l2o-dioni Diproderm=9-fluoro-llbeta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dion-17,21-dipropionate; Diploren) which can S be used for the treatment of all types of psoriasis.
These drugs have symptomatic effect and relatively shortly after interrupting the treatment recidivation takes place, their long-lasting use, however, can result in atrophy of the connective tissues, and certain habituation to it can also be observed. Therefore for long-lasting treatment only steroides showing less side-effects (e.g. Hydrocortison, Prednisolon) are suitable.
Treatment with systemic corticosteroids can be taken into consideration only in complicated cases, but only for short period. -For the time being the most frequently used agentsfor systemic treatments - exclusively in severe cases -are the aromatic derivatives of vitamine A, the so called retinoids (e.g. Tigason=etretinate). These drugs, however, can only be applied very carefully as they have serious side effects (e.g. increase of the serum lipid level, hypertension, teratogenesis).
According to the aforementioned the treatment of psoriasis has not been solved sufficiently yet. All the known compositions have side effects, and the fact that only a few topical compositions are known proves that good results can be achieved only with the oral composit:ions.
The object of our invention was to ensure a topical composition for the treatment of psoriasis.
Further object of our invention was to develop a composition without any harmful side e~fect (e 9 g.
carcinogenic, teratogenic, bone marrow damaging, adrenal disfunction producing effect, etc.) during the use of which no pigmentation, dehydratation, atrophy, super~
.:
, W092/03l42 PCT/HU9l/00038 2~ 7~ - 6 -infection on the injured skin surface occur and its application is not limited by interaction with other drugs.
Surprisingly it has been found that a composition comprising the aqueous and/or pharmacologically accept-able organic solvent, preferably ethanolic extract of the young crop and/or beard (silk) and/or nodulous stalk and/or cob of maize plant and gamma-linolic acid can be used for the treatment of psoriasis without any side effect.
It is known from HUP No. 195,915 (USP No. 4,950,481) that the aqueous and/or ethanolic extract of the young crop and/or bread and/or nodulous stalk and/or cob of maize possesses skin sedative and skin regenerative effect.
The aqueous and/or ethanolic extract comprises the following active ingredients:
- carbohydrates (mono- and oligosacharides, poly-sacharides), - fats, oils, fatty acids (phospholipides, glycolipides, galactolipides), - proteins, amino acids, - phenolic materials (~lavonoides, coumarines, phenyltropanes and the phenolic materials), - terpenes (sesquiterpenes, triterpenes, te~ra-terpenes), -- vitamins, volatile oils.
Out of the above components first of all the poly-sacharides and flavonoides possess antiphlogistic effect.
The phospholipids are emulsifiers and are frequently used in cosmetic compositions as additives.
The gamma-linolic acid is an essential amino acid and being "body-friend" (histotropic), has no harm~ul - side effect.
The O~nothera oil containing gamma-linolic acid has '- ' - ' :
2~7~7~
been successfully used mainly for the treatment of different complicated and uncomplicated cardiovascular diseases. It was able to decrease the thrombocyte aggregation, to normalize the lipid levels, however in the popular therapy it has been also used as oral antispasmodic and antiphlogistic agent.
Surprisingly the corn extract used so far in cosmetic compositions and having mild antiphlogistic effect, together with gamma-linolic acid is efficient in lo the treatment of uncomplicated psoriasis diseases and after the treatment the patients became symptomless. As the composition contains only natural active ingredients it has no side effect. The active ingredients of the composition according to the invention separately are not able to ensure the desired effect, they are effective against psoriasis only in case of their common use.
Accordingly the invention relates to pharmaceutical compositions suitable for the topical treatment of psoriasis which comprises an aqueous and/or pharma-ceutically acceptable organic solvent, preferablyethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob together with gamma-linolic acid as active ingredient admixed -with one or more solid and/or liquid carrier(s) and/or additives.
Concentration of the active ingredient is preferably lS-75~ by weight.
A further object of the invention is a process for the preparation of a pharmaceutical composition suitable ~or the topical treatment of psoriasis in which the aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn~crop - and/or corn-beard and/or nodulous corn-stalk and /or corn-cob and gamma-linolic acid as active ingredient are admixed with one or more soli~ and/or liquid carrier(s) W092/03]42 PCT/HU91/00038 2~
and/or additive(s) and the mixture thus obtained is formed into cream, emulsion or solution suitable for topical use.
The corn extract used in the composition according to the invention can be prepared in a manner known per se, eOg. the method described in US P No. 4,590,481 can be used.
The extract can be prepared e.g. by extracting the optionally dried plant pieces with a 2-30-fold amount -calculated for the dry mass of the plant - of water or aqueous solution of a cosmetically acceptable organic solvent at a temperature between 15 and 95C and separating the solid phase ~plant pieces) from the liquid phase.
Alternatively, the extract can also be obtained as follows: plant pieces are crushed and steeped in the above mentioned solvents. The time of steeping can vary within a wide range, preferably between 5 and 48 hours.
On industrial scale the extraction is preferred as it can be carried out within a shorter time, (e.g. 30-60 minutes).
After the extraction or steeping the product obtained may be sterilized by heating it one or more times, preferably three-times to 80C and heating it at this temperature for a short period.
For the extraction generally water or the aqueous solution of a water-miscible pharmaceutically acceptable organic solvent, e.g. ethanol is used.
The pharmaceutical sompositions according to the invention contain the active inyredient and one or more pharmaceutically acceptable solid and/or liguid carrier~s) and/or additives.
The compositions according to the invention may contain as solid carrier for example talc, zinc oxide, bentonite, Xaolin, colloidal silica, titanium-dioxide;
W092/03142 2~ 77~ PCT/HU91/00038 _ g _ corn-starch, potato starch. Solid emulsifying agents, e.g. fats, fatty alcohols, fatty acid, fatty acid esters, waxes can also be used as solid carriers.
The compositions according to the invention may contain as liquid carrierc~ one or more pharmaceutically acceptable, to the skin non-irritative liquid solvent(s), e.g. water, ethanol or animal or vegetable oil.
The compositions according to the invention may contain as carrier and emulsifier respectively in the cosmetic industry generally used fats, oils, waxes, fatty acids and esters and glycerides thereof obtained with higher alcohols.
The fatty acids m~y be straight or branched having 12-18 carbon atoms, may be saturated or unsaturated and may also be substituted with one or more hydroxy group(s).
Suitable fatty acids are selected from the group ` ;
consis~ing of undecenoic acid, laurylic acid, caprylic acid, myristic acid, palmitic acid, isopalmitic acid, stearic acid, isostearic acid, hydroxy stearic acid, oleic acid, hydroxy-oleic acid, behenic acid, lanolinic acid, arachidonic acid, octyldecanoic acid, pentadecanoic acid or the mixture thereo~.
Suitable fatty acid-esters are selected from the group consisting of isopropyl myristate, butyl myristate, octyldodecyl myristate, isocetyl myristate, cetyl myristate, ethyl palmitate, isopropyl palmitate, hexadecyl stearate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, cetyl ricinoleate, propylenglycol dipelargonate, 2-ethylhexyl isononate, hexyl laurate, 2-ethylhexyl stèarate, ~atty alcohol lactate having 12-16 carbon atoms, triglycerides of octanoic and dekanoic acids salicylate and the mixture thereof.
: :
.~ ..
, ;. .:
, ~'.
, 2~7~ o -As fatty alcohol e.g. alkohols having 14-22 carbon atoms, e.g. behenyl alcohol, myristyl alcohol, arachidyl alcohol, steary:L alcohol, isostearil alcohol, cetyl alcohol, cetyl-stearyl alcohol, isoce'~l alcohol, oleyl alcohol, lauryl alcohol may be mentioned.
As liquid carrier various oils or oil mixtures applied generally in the cosmetic industry can also be used. The oils act as stabilizing agent in the emulsions and ensure a cosmetically suitable viscosity for the emulsion.
Suitable oils are selected from the group consisting of aliphatic hydrocarbons (e.g. liquid paraffine, vaseline, ceresine etc), vegetable oils and fats (e.g.
olive oil, almond oil, wheat-germ oil, corn-germ oil, cotton-seed oil, grape-stone oil, jojoba oil, avocado oil, castor oil, palm oil, cocoa butter etc.), animal fats and oils (e.g. cod-liver oil, blubber oil, butyrine, etc.) The compositions according to the inven~ion may contain as other additives e.g. one or more hygroscopic material(s), solubilizing and stabilizing agent, -preservative, disinfectant, skin sedating, skin protecting, epithelium regenerating, skin re-fatting, light-protecting and aromatizing materials, vitamins, etc.
As hygroscopic materials e.g. glycerol, sorbitol, propylene glycol may be used.
As solubilizing material e.g. butyl-hydroxy-anisole, butyl-hydroxy-toluene, ethylene-diamine-tetraacetic acid, nor-dihydroguaiaretic acid may be used.
A preservative e.g. methyl parabene, p-hydroxy-benzoic acid and esters thereof, chloromethyl-iso-thiazoline, methyl-isothiazoline, phenoxetole, hexetidine, chlorohexidine-gluconate, imidazolinyl urea can be used. I~ desired formaldehide and similar other W O 92/03142 ~ 7~ PC~rtH U91/00038 , .
preservatives may also be used.As tonic or disinfectants e.g. menthol, camphor, lactic acid, citric acid, ethanol can be used.
As epithelium regenerating material e.g.
allanthoine, panthenol, calcium pantothenate can be used.
As skin sedating material e.g. chamomile extract, azulenole, bisabolole can be used.
As skin protecting and re-fatting matexial e.g.cholesterol, propane-3-carboxymethyl-betaine, 1--(alkylamino)-3-(dimethylamino)-propane-3-N-oxide, propane-3-(carboxymethyl)-betaine, alkyl-dimethylamin-oxide, mono- and di-ethanolamide of cocoa acid can be used.
As light protecting (sunscreening) material e.g.
octyl-dimethyl-PABA, 2-hydroxy-4-methoxy-benzophenone, 2-(ethyl-hexyl)-3-(4-methoxy-phenyl)-2-propenoate, 1-(4-methoxy-phenyl)-3-(4-tert-butyl-phenyl)-propane-1,3-dione, urocainic acid, esculine can be used.
As vitamin, e.g. A, B, Bl, C, E, F, H, P vitamin can be used.
~ s aromatizing material e.g. parfume oil can be used which ensures a pleasant and attractive smell for the composition.
The composition according to the invention can be formulated into different forms suitable for topical treatment, eOg. cream, ointment, emulsion, solution, tonic, gele, etc. can be prepared.
The creams and the ointments according to the invention contain 30-70~ by weight of corn extract and 0.05-3~ hy weight of gamma-linolic acid as active ingredient. ~, The emulsions according to the invention contain 15--30% by weight of corn extract and 0.05-3~ by weight of gamma-linolic acid as active ingredient.
~ 35 The solutions according to the invention contain .
. .
2~'S~7~7~ - 12 -preferably 30-50% by weight of corn extract and 0.05-3%
by weight of gamma-linolic acid as active ingredient.
The amount of water and aqueous solvent used in the compositions depends on the consistency of the desired s end product. The water used is preferably deionized water and the amount thereof is generally 27-75~ by weight calculated for the total amount of the composition. The cream and ointment compositions contain generally at least 20~ by weight but max. 60% by weight of water, the water content of the emulsions is prefera~ly 50-70% by weight and that of the solutions preferably 40-70~ by weight.
The following non-limiting Examples show the compositions of the invention.
The corn extracts used in Examples 1, 2 and 3 were prepared according to Example 1 o~ HU P No. 195,915 `~
(using water as extraction solvent), the corn extract used in Example 6 was prepared according to Example 6 of said patent specification (using ethanol as solvent) and the corn extract used in Examples 4, 5 and 7 were prepared according to Example 3 of the same patent specification.
The corn extracts used in Examples 1-5 were prepared from the crops, hypsophylls, cob, beard and nodulous stalk o~ the young corn plant, for the preparation of corn extracts used in Example 6 and 7 hypsophylls and crops of corn plant, and hypsophylls, cob and beard respectively, were used.
The products specified with trade marks contain the followiny compounds:
Hostacerin WO: fatty acid-polyglycerol ester (Hoechst AG, DE) Lanette N: mixture of sodium-cetyl-stearyl sulfate and cetyl-stearyl alcohol (Henkel, DE) BRIJ71: ethoxylated stearyl alcohol ~JCI, USA) W092/03142 2~777~ PCT/HU91/00038 BRIJ72l: ethoxylated stearyl alcohol (JCI, USA) Chremophor W07: hydrogenated castor oil (BASF, DE) Genagol AMS: detergent and surfactant (Hoechst, DE) Hoe S 3495: ethoxylated fatty acid-polyglycerol ester (Hoechst, DE) Examplo l Cream for day Composition: amounts (g) Corn extract 45.0 Gamma linolic acid O.lO
Cetyl alcohol 7.65 .
Stearin 2.35 Castor oil 4.00 Yaseline oil 6.00 Corn-germ oil 5.00 Na-lauryl sulfate l.00 Glycerol 5.00 Cholesterol l.00 Vitamin A 0.05 Vitamin E O.lO .
Preserving, aromatizing material 0.20 -Deionized water ad lO0.00 :i:
~5 Example 2 --~.
Night creau Composition: amounts (g) Corn extract 60.00 Gamma linolic acid 0.12 Hoctacerin WO lO.O0 Light vaseline 5.00 ;
Lanette N 2.00 :
Avocado oil lG.00 .
Vaseline oil 4.00 Wheat-germ oil 5.09 - , ':
' E~ample 2 continuad Composition: amounts (g) Cholesterol 3.00 Glycerol O.lO
Vitamin A 0.05 Vitamin E 0.05 Preserving, aromatizing material 0.02 Deionized water ad lO0.00 Example 3 Body lotion Composition: amounts (g~
Corn extract 40.00 Gamma-linolic acid O.lO
Cetyl alcohol l.50 Castor oil l.S0 Corn-germ oil 3.00 Vaseline oil l.00 BRIJ 72 2.50 BRIJ 721 l.60 Soorbitol 5Ooo Glycerol 6.00 - Vitamin A 0.05 ~ -Vitamin E 0.05 Preserving, aromatizing material 0.20 Deionized water ad lO0.00 Example 4 Emul3ion Composition: amounts (g) --Corn extrac_ 15.00 Gamma-linolic acid O.l5 Chremophor WO 7 6.00 Avocado oil 4.00 Corn-qerm oil 3.00 ~; .
, , ' W O 92/03]42 2~S777'~ PC~r/H U91/00038 Example 4 conti~ued Composition: amounts (g) Vaseline oil 14.00 Cetyl alcohol 1.00 Propyleneglycol 4.00 Vitamin A 0 05 Vitamin E ~.07 Preserving, aromatizing material 0.20 Deionized water 100.00 Example 5 Solution for medical tr~atment Composition: amounts (g) ~:
Corn extract 35 00 -Gamma-linolic acid 0.08 Izopropyl-alcohol 5.00 Menthol 0.03 Camphor 0.02 Sar~oxethene laurate 2.00 :
Propyleneglycol 10.00 Vitamin B1 0.10 ::
Preserving, aromatizing material 0.20 : .
Deionized water ad 100 ~a~ple 6 . :
~olution Composition: amounts (g) Corn extract 30.00 Gamma-linolic acid 0.10 Izopropyl-alcohol 5.00 -Ethanol 19.00 Menthol 0~05 Lactic acid 1.00 Sorboxethene-laurate 0.50 ..
Propylene glycol 10.00 - ' ' . - .:
2~77~ - 16 - ' Example 6 continued Composition: amounts (g) Preserving aromatizing material 0.20 Deionized water ad 100.00 Example 7 8hampoo Composition: amounts (g) Corn extract 75.00 Gamma-linolic acid 0.08 Na-lauryl sulfate 10.00 Genagol AMS 5.00 Hoe S 3495 1.00 Panthenol 2.00 Propane-3-carboxymethyl-betain5.00 Methyl-p-hydroxy-benzoate 0.20 Aromatizing material 0.50 Deionized water ad lOO.OO
The effect of the composition according to the invention were proved by the following clinical tests.
Experime~t 1 The composition according to Example 1 was tested on 11 female patients of the age of Z1 to 68 years and on lO male patients of the age of 33 to 73 years. The patients suffered from psoriasis for 12 years on an average. Tbe cream was applied to the injured skin surface 3 times a day and the treatment was continued for 3 wee~s. The results obtained are summarized in Table 1. The abbreviations used have the following meaning:
N- number of the patients suffering from the given type of psoriasis CI= considerable improvement WO92/03142 PCT/~U91t~0038 ~7~
SI= slight improvement D= deterioration Table 1 Type of psoriasis N CI SI D
Plaque disseminatio 11 7 1 3 ~rithroderma psoriaticum 2 Guttata disseminatio 2 10 Seborrhea typ. 1 1 - -Palmoplantaris typ. 4 4 Psoriasis localized to limbs 1 1 - -Total 21 15 3 3 It appears from the above Table that the condition of 71% of the patients improved considPrably, in case of 15~ a slight improvement and in case of 14%
deterioration was observed. Especially good results were obtained in connection with the seborrhoea type and palmoplantaris type psoriasis as well as in case of psoriasis localized to limbs.
Comparati~e experiment 2 For comparison, the composition according to Example 1 but containing 45.0 g wheat-germ oil instead of 45 g corn extract was tested on 10 male patients of the age of 32-70 years and on 10 female patients of the age of 20-65 years. The patients suffered from psoriasis 30 for 11 years on an average. The cream was applied to the - ;~
injured surface 3 times a day and the treatment was continued for 3 weeks. The results obtained are -~
summarized in Table 2. -. ~ :.
Table ~
";
2a?~777~ i -Type of psoriasis N CISI D
Plaque disseminatio 8 1 4 3 Erithroderma psoriaticum 2 Guttata disseminatio 2 5 Seborrhea typ. 3 Palmoplantaris typ.
Psoriasis localized to limos 4 1 1 2 Total 20 3 9 8 From the above Table it appears that the number of patients showing considerable improvement decreased (to 15%), the number of patients showing slight improvement increased (to 45~) and the amount of patients with deteriorated condition increased to 40~. Considerable improvement could be achieved only in case of one patient suffering from plaque disseminatio, seborrhoea type psoriasis and psoriasis localized to limbs, due to the skin sedative effect of the cream mostly slight improvement could only be achieved.
According to the aforementioned it can be established that the gamma-linolic acid without corn extract is not suitable for the treatment of psoriasis.
Comparative experiment 3 For further comparison the composition according to Exampl~ l but containing O.Ol g of wheat-germ oil instead of O.1 g gamma-linolic acid was tested on 13 male patients of the age of 28 to 60 years and on 7 female patients of the age of 22 to 67 years. The patîents suffered from psoriasis for 11 years on an average. The cream was applied to the injured skin surface 3 times a day. The treatment was continued for 3 weeks. The results obtained are summarized in Table 3.
. .
-WO92/03142 ~ 7 7 ~ PCT/HU9l/00038 !
Tahle 3 .
Type of psoriasis N CI SI D
Plaque disseminatio 10 3 4 3 5 Erithroderma psoriaticum 3 - 2 Guttata disseminatio 1 - -Seborrhea typ. 2 Palmoplantaris typ. 2 Psoriasis localized 10 to limbs 2 Total 20 3 9 8 From the above Table it appears that the number of patients showing considerable improvement decreased (to 15~), the number of patients showing slight improvement increased (to 45~) and deterioration was established in 40% of the patients. Considerable improvement could be achieved only in case of plaque dissemination, in other cases the slight improvement was proba~ly due to the :
mild antiphlogistic effect of the corn extract.
The above Table clearly shows that th~ anti-phlogistic effect of the corn extract alone is not able to decrease the occurrence of symptoms of different types of psoriasis, the composition containing no gamma--linolic acid possesses less activity than the composition according to Example 1.
~perime~t 4 The composition according to Example 6 was tested on 16 male patients aged from 3Q to 60 years and on 13 female patients of the age of 22 to 60 years. The patients suffered from scalp psoriasis, for 10 years on the average. The solution was applied 3 times a day and the treatment was continued for 3 weeks. The results obtained are summarized in Table 4.
- ':
.
Table 4 Strength of the Before After symptoms treatment Medium Nild Medium Mild Parakeratosis 9 20 5 o Infiltration 9 20 7 o Burning 3 20 2 0 Itching 7 20 5 3 The Table clearly shows that the solution according to Example 6 has eliminated the mild parakeratosis, infiltration, burning and itching in all the 20 patients. That means that in case of mild symptoms an efficiency of 100% can be achieved.
In case of medium parakeratosis and infiltration lOO~ efficiency was achieved in 4 and 2 patients respectively out of 9 patients, however in ease of medium burning the symptoms were totally eliminated in 1 . .
patient out of 3 patients.
Treatment of patents sufferin~ from extremely serious alteration was not carried out at all as according to clinical experiences such cases can be made symptomless - for a short period - only by systemic :.
treatment.
':
Claims (27)
1. Pharmaceutical composition suitable for the topical treatment of psoriasis which comprises an aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob and gamma-linolic acid as active ingredient admixed with one or more solid and/or liquid carriers and/or other additives.
2. Composition as defined in Claim 1 which comprises the aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob and gamma-linolic acid acid in an amount of 15-75% by weight calculated for the total amount of the composition and in a weight ratio from (100:1) to (950:1).
3. The composition as defined in Claim 1 or 2 which comprises the aqueous extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob.
4. The composition as defined in any of Claims 1-3 which comprises 30-70% by weight of corn extract and 0.05-3%by weight of gamma-linolic acid as active ingredient.
5. The composition as defined in any of Claims 1-3 which comprises 15-30% by weight of corn extract and 0.0503% by weight of gamma-linolic acid as active ingredient.
6. The composition as defined in any of Claims 1-3 which comprises 30-50% by weight of corn extract and 0.0503% by weight of gamma-linolic acid as active ingredient.
7. The composition as defined in any of Claims 1-6 which comprises natural or synthetic fats, oils, fatty alcohols, fatty acid ester and/or the derivatives thereof as carrier and/or emulsifying agent.
8. The composition as defined in Claim 7 which comprises cetyl alcohol, cetyl-stearyl alcohol, fatty acid-polyglycerol ester, sodium-cetyl-stearyl sulfate, stearin, castor oil, avocado oil, wheat-germ oil, vaseline oil, corn-germ oil and/or light vaseline as carrier.
9. The composition as defined in any of Claims 1-8 which comprises one or more emulsifier(s), solubilizing, hygroscopic, skin and epithelium regenerating, aromatizing, disinfecting material, preservatives and/or vitamin as other additives.
10. The composition as defined in Claim 9 which comprises sodium-lauryl sulfate, sodium-lauryl ether-sulfate, ethoxylated stearyl alcohol, hydrogenated castor oil and/or etoxylated fatty acid-polyglycerol ester as emulsifier and solubilizing agent respectively.
11. The composition defined in Claim 9 which comprises glycerol, sorbitol and/or propylene glycol as hygroscopic material.
12. The composition as defined in Claim 9 which comprises cholesterol, panthenol and/or propane-3-car-boxymethyl-betain as skin and epithelium regenerating material.
13. The composition as defined in Claim 9 which comprises A, E, and/or B1 vitamin and menthol, camphor and/or lactic acid as disinfectant.
14. Process for the preparation of pharmaceutical compositions suitable for topical treatment of psoriasis which comprises admixing an aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob and gamma linolic acid as active ingredient with one or more solid and/or liquid carrier(s) and/or other additives and converting the mixture thus obtained into a form suitable for topical application, preferably into a cream, emulsion or solution.
15. The process as defined in any of Claims 13-14 which comprises using aqueous and/or pharmaceutically acceptable organic solvent, preferably ethanolic extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob and gamma-linolic acid acid in an amount of 15-75% by weight calculated for the total amount of the composition and in a weight ratio from (100:1) to (950:1) as active ingredient.
16. The process as defined in any of Claims 14-15 which comprises using the aqueous extract of young corn-crops and/or corn-beard and/or nodulous corn-stalk and/or corn-cob.
17. The process as defined in any of Claims 14-15 which comprises using 30-70% by weight of corn extract and 0.05-3%by weight of gamma-linolic acid as active ingredient.
18. The process as defined in any of Claims 14-15 which comprises using 15-30% by weight of corn extract and 0.05-3% by weight of gamma-linolic acid as active ingredient.
19. The process as defined in any of Claims 14-15 which comprises using 30-50% by weight of corn extract and 0.05-3% by weight of gamma-linolic acid as active ingredient.
20. The process as defined in any of Claims 14-19 which comprises using natural or synthetic fats, oils, fatty alcohols, fatty acid ester and/or the derivatives thereof as carrier and/or emulsifying agent.
21. The process as defined in Claim 20 which comprises using cetyl alcohol, cetyl-stearyl alcohol, fatty acid polyglycerol ester, sodium-cetyl-stearyl sulfate, stearin, castor oil, avocado oil, wheat-germ oil, vaseline oil, corn-germ oil and/or light vaseline as carrier.
22. The process as defined in any of Claims 14-21 which comprises using one or more emulsifier(s), solubilizing, hygroscopic, skin and epithelium regenerating, aromatizing, disinfecting material, preservatives and/or vitamin as other additives.
23. The process as defined in Claim 22 which comprises using sodium-lauryl sulfate, sodium-lauryl ethersulfate, ethoxylated stearyl alcohol, hydrogenated castor oil and/or ethoxylated fatty acid-polyglycerol ester as emulsifier and solubilizing agent respectively.
24. The process as defined in Claim 22 which comprises using glycerol, sorbitol and/or propylene glycol as hygroscopic material.
25. The process as defined in Claim 22 which comprises using cholesterol, panthenol and/or propane-3-carboxymethyl-betain as skin and epithelium regenerating material.
26. The process as defined in Claim 22 which comprises using A, E, and/or B1 vitamin as vitamin.
27. The process as defined in Claim 22 which comprises using menthol, camphor and/or lactic acid as disinfectant.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU905312A HU205860B (en) | 1990-08-24 | 1990-08-24 | Process for producing pharmaceutical compositiojns for topical treating psoriasis |
| HU5312/90 | 1990-08-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2067770A1 true CA2067770A1 (en) | 1992-02-25 |
Family
ID=10970056
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002067770A Abandoned CA2067770A1 (en) | 1990-08-24 | 1991-08-23 | Composition for the topical treatment of psoriasis |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0497952A1 (en) |
| JP (1) | JPH05503295A (en) |
| CA (1) | CA2067770A1 (en) |
| CS (1) | CS261891A3 (en) |
| HU (1) | HU205860B (en) |
| IL (1) | IL99236A0 (en) |
| PT (1) | PT98757A (en) |
| WO (1) | WO1992003142A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6383499B1 (en) * | 1995-10-30 | 2002-05-07 | Curacid America Corporation | Topical medicament for the treatment of psoriasis |
| US6277418B1 (en) * | 1998-06-02 | 2001-08-21 | Baylor College Of Medicine | Corn extract contraceptive |
| ITBS20130144A1 (en) * | 2013-10-14 | 2015-04-15 | Alejandro Jorge Outon | PREPARATION FOR THE TREATMENT OF PSORIASIS |
| KR101839109B1 (en) * | 2016-09-22 | 2018-03-15 | ㈜프론트바이오 | Composition for preventing or treating skin disease, comprising extract of purple corn |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH655245A5 (en) * | 1981-10-23 | 1986-04-15 | Oreal | ANHYDROUS, OXIDATION-STABLE COMPOSITION, BASED ON AN ANTHRALINE COMPOUND IN A SUPPORT CONSISTING OF A FATTY ACID ALKYL-ESTER AND A THICKENING AGENT. |
| GB8420771D0 (en) * | 1984-08-15 | 1984-09-19 | Efamol Ltd | Treatment of skin disorders |
| HU195915B (en) * | 1984-09-21 | 1988-08-29 | Tibor Keri | Cosmetic preparation of skin regenerating and hydrating effect |
| DE3512743A1 (en) * | 1985-04-09 | 1986-10-16 | Goebel Hans Joachim | Composition for the external treatment of psoriasis |
| DE3836519C2 (en) * | 1988-10-26 | 1994-03-10 | Cutan Kosmetik Vertriebs Gmbh | Use of a pharmaceutical preparation based on Calendula officinalis for the treatment of psoriasis |
-
1990
- 1990-08-24 HU HU905312A patent/HU205860B/en not_active IP Right Cessation
-
1991
- 1991-08-20 IL IL99236A patent/IL99236A0/en unknown
- 1991-08-23 CS CS912618A patent/CS261891A3/en unknown
- 1991-08-23 JP JP3513682A patent/JPH05503295A/en active Pending
- 1991-08-23 WO PCT/HU1991/000038 patent/WO1992003142A1/en not_active Application Discontinuation
- 1991-08-23 PT PT98757A patent/PT98757A/en not_active Application Discontinuation
- 1991-08-23 EP EP91915231A patent/EP0497952A1/en not_active Ceased
- 1991-08-23 CA CA002067770A patent/CA2067770A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0497952A1 (en) | 1992-08-12 |
| PT98757A (en) | 1992-07-31 |
| IL99236A0 (en) | 1992-07-15 |
| WO1992003142A1 (en) | 1992-03-05 |
| CS261891A3 (en) | 1992-03-18 |
| HU205860B (en) | 1992-07-28 |
| HU905312D0 (en) | 1991-02-28 |
| JPH05503295A (en) | 1993-06-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |