AU610632B2 - Improvements in or relating to methods of treating damaged skin - Google Patents
Improvements in or relating to methods of treating damaged skinInfo
- Publication number
- AU610632B2 AU610632B2 AU21184/88A AU2118488A AU610632B2 AU 610632 B2 AU610632 B2 AU 610632B2 AU 21184/88 A AU21184/88 A AU 21184/88A AU 2118488 A AU2118488 A AU 2118488A AU 610632 B2 AU610632 B2 AU 610632B2
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- skin
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Classifications
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- 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
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/004—Aftersun preparations
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Abstract
Compounds of the formula <IMAGE> in which Z and n have the meanings defined in the description, can be used as active ingredients in products for topical treatment of skin damaged by light.
Description
PATENT AND TRADE MARK ATTORNEYS
SYDNEY
A.S.C.-2
G--
~.mm Ai
AUSTRALIA
olO 632 PATENTS ACT 1952 COMPLETE SPECIFICATION
(ORIGINAL)
FOR OPiFICE USE Application Number: Lodged: Complete Specifica~tion Lodged: Accepted: Published: Priority: Related Art: Elli t Name of Applicant: Address of Applica .W Actual Inventor: Address for Servic TO BE COMPLETED BY APPLICANT F, k efd iHOFFMANN-LA ROCHE CO.
-AKTIENGESELLSCHAFT-
Lnt: 124-184 Grenzacherstrasse, Basle, Switzerland, Graeme Findlay Bryce Stanley Seymour Shapiro e: ARTHUR S. CAVE CO.
Patent Trade Mark Attorneys Level Barrack Street SYI)NEY N.S.W. 2000 AUSTRAL IA Complete Specification for the invention entitled G~P~CUIATL The following statement is a full description of this invention including the best method o performing it known to me:- A8C 49 ey I' 1 -rr J ~Ju 1~ in paragrapn or tnis Declaration was/were the first application(s) made in a Convention country in respect of the invention s) the subject of the application.
To: Declared at Basle, The Commissioner o' Patents, COMMONWEALTH OF AUSTRALIA this 12th day of July, 1988 De larant( Signature of Delarant(s) RAN 4051/17 The skin, particularly in humans, contains an elaborate network of elastin fibers which are responsible for maintaining its elastic properties. With excessive exposure to sunlight the elastic fiber system becomes hyperplastic, disorganized and ultimately disrupted. This is known as actinic elastosis and is the principal cause of wrinkling, discoloration and laxity of the skin in the exposed areas of the body. The skin can repair itself to some extent but it is nevertheless desirable to have an agent which can accelerate the repair of this prematurely aged skin.
r-- 44, 4 44 The UVB irradiated hairless mouse has been found to be a convenient model for actinic elastosis in the skin. (Kligman et al. J. Invest. Dermatol. 78:181 (1982). It has been shown by Johnston et al. in J. Invest. Dermatol. 82:587 (1984) that irradiation with low levels of UVB which simulate realistic solar exposure leads to a sirnificant increase in skin elastin as measured by demosine content. The amount of this amino acid, which is isolated from acid hydrolysis of elastin, is proportional to the elastin present in the skin.
(Uitto et al., Lab. Invest. 49:1216 (1973). Treatment of irradiated mice with topical retinoic acid has been shown to normalize the histological features of the skin in which the previously elastotic dermis has the appearance of unirradiated tissue (Kligman et al., Conn. Tissue Res. 12:139 30 (1984), Kligman U.S. Patent No. 4,603,146 July 1986).
Therefore this model can be used to determine the efficacy of compounds in the repair of sum damaged skin.
Grn/21,6.88 4 44 4,4 4i 44 4 44 4d t 4 44~ 4 44 44 41 *44I1 I 441 44 4 *41 44 $L 4 la 2 In accordance with this invention, it has been found that compounds of formula (CH'J I wherein n represents 1 or 2; Z represents R, wherein m represents 0, 1 or 2; R m represents lower-alkyl, lower-alkenyl, lower alkynyl lower-alkoxy-lower-alkyl, lower-alkanoyl-lower-alkyl, hydroxy-lower-alkyl, halo-lower-alkyl, lower-carbalkoxy-lower-alkyl or, when m is 1 or 2. R represents also lower-alkoxy, hydroxy, itono-lower-alkyl amino or di-lower-alkylamino, and pharmaceutically acceptable salts thereof oeo when applied topically to the skin of a patient reverse the conditions associated with photodamage. Hence, by the topical application of compounds of formula I to the skin of patients which has been damaged through sun exposure, the .o effects of wrinkling, elastosis and ptemature aging can be reversed leading to an improvement in the appearance of the skin.
o 30 Through the topical administration of the compounds of °o the formula I, the acceleration of repair of dermal damage is accomplished so as to provide the skin with a smoother and o0 8o younger appearance.
4 3 The term "lower" as used herein denotes groups which preferably contain 1-4 carbon atoms. Alkyl groups can be straight-chain or branched-chain. Preferred lower-alkyl grouos are methyl, ethyl and isopropyl. Examples of lower-alkenyl groups are vinyl, allyl and methallyl.
Examples of lower-alkanoyl groups are acetyl, propionyl, and butyryl. Alkynyl groups can be straight-chain or branched-chain. Preferred lower alkynyl groups are ethynyl and propynyl. The term "halogen" embraces fluorine, chlorine, bromine and iodine, of which chlorine is preferred. Examples of lower-carbalkoxy-lower-alkyl groups are carbomethoxy- and carboethoxy-methyl and -ethyl.
Examples of lower-alkoxy groups are methoxy and ethoxy.
Examples of alkylamino groups are methylamino, ethylamino, isopropylamino, dinethylamino and diethylamino.
The present invention is accordingly concerned with the compounds of formula I or pharmaceutically acceptable salts thorof for use in the topical treatment of conditions associated with photodamaged skin and for the manufacture of pharmaceutical preparations for topical application intended 0 ofor the treatment of such conditions. The invention is also Sconcerned with a method of treatment of the conditions Sassociated with photodamaged skin by topically administering a compound of the formula I or a pharmaceutically acceptable salt thereof to an area of the skin of a patient in neod of said treatment.
A pharmaceutically acceptable salt of compounds of 30 formula I, which compounds belong to the class of retinoids, o"0 includes any salt chemically permissible in the art for compounds of formula I and applicable to human patients in a pharmaceutically acceptable preparation. Among such pharmaceutically acceptable salts of compounds of formula I there are especially included salts of sulfonic acids and sulfinic acids of compounds of formula I. Any conventional pharmaceutically acceptable base salt of sulfonic or 4sulfinic acids of compounds of formula I a be utilized.
Among the conventional base salts which can be utilized there are included, for example, alkali metal salts such as sodium or potassium, alkaline :.1'rth metal salts such as calcium or magnesium, and ammonium or alkyl ammonium salts.
Furthermore, conventional acid addition salts, such as acetates, may be utilized for compounds of formula I wherein R is mono- lower-alkylamino or d i-lower -a lkyl-aimino.
In a particular aspect, this invention relates to the compounds of formula I and their salts except the compound ethyl p-f2-(5,6,7,8-txitrahydro-5,5,8,8-tetramethyI -2-naphthyl) propenyll~phenylsuif one.
Of the compounds of formula I wherein Z represents mR, there are preferred those compounds in which R is lower-alkyl, lower-alkenyl, hydroxy-lower-alkyl, or, when m is 1 or 2, lower-alkoxy, hydroxy, mono- lower-a lkylamino or di-lower-alkylamino.
Furthermnore, there are especially preferred compounds of formula I in which m is 2 as well as those in which R is lower-alkyl except ethyl. Further preferred compounds of formula I are those in which n ot formula I is 2.
Especially preferred is meth~yl p-(2-(5,6,7,8-tetra- 8, 8-tetramethyl-2-naphthyl)propenyllphanylsulf one.
other interesting compounds of Formula I are ethyl p-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl 0 00 -2--naphthyl )propenyl Jphenylsulfonaate; ethyl p-(2-(S,6,7,8-tetrahydro-5,5,8,8-tetramethyI -2-raphthyl) propenyl Jphenylsulf(,ne; ethV'1 p-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl -2-naphthyl)propenyljlphenylsulfoxide;
L
ethyl p-[2-(5,6,7,,8-tetrahydro-5,5,8,8-tetramethyl -2-naphthyl)propenyl]phenylsulfide; isopropyl p-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl -2-naphthyl)propenyl]phenylsulfone.
Processes for preparing compounds of Formula I are set forth in U.S. Patent No. 4,395,553.
The compounds of the formula I when applied topically to the skin, reverse the conditions associated with photodamage so as to moderate and retard the damage to the skin caused by sun exposure. The damage caused by sun exposure may include premature aging, elastosis and wrinkling. This damage is more pronounced in older patients. By applying the compounds of formula I topically to the skin in an amount effective to reverse the conditions associated with photodamage, the acceleration of skin repair is accomplished to enhance the skin with a smoother and younger appearance. The compounds of formula I should be applied to that portion or a-ea of <.he skin which is affected by photodamage or in which treatment is desired. The use of the compounds of formula I in o accordance with this invention can provide the effects of anti-aging and anti-wrinkling, as well as enhance the repair of sun damaged skin.
A compound of formula I, or a combination of compounds of formula I can be applied in accordance with this invention to human skin in conventional topical compositions. These compositions can be utilized to apply compounds of formula I S 30 to the skin of the body, particularly the face, legs, arms and hands. The preferred method of application of compounds of formula I topically to produce. the best effects should ao start where a patient is between 30 and 55 years of age, when slastosig begins to appear and becomes more pronounced.
Thereafter, ,kis composition can be continuously applied to "o patients to reduce the effects and injury associated with sun 4 4 6 6 exposure. Generally, it is preferred to begin the treatment when the patient reaches approximately 30 years of age and to continue the treatment throughout his life, in order that the effects of elastosis be reduced and to prevent any further progression of photodamage.
The compounds of formula I can be administered in accordance with this invention in any conventional suitable topical preparation, i.e. in combination with any suitable conventional carrier useful for topi'al administration, Therefore, compounds of formula I can oe administered in accordance with this invention in any suitable topical composition such as a cream, ointment, soap, solution, lotion, emulsion, shampoo, etc. Generally, for most efficacious results, these topical compositions contain from about 0.00001% to about 1.0% by weight of the total composition of a compound of formula I, with amounts of from about 0.0001% to about 0.1% by weight of the composition being especially preferred. If desired, higher co.centrations may be utilized depending upon the nature and extent of elastosis.
In formulating these compositions, any conventional non-toxic, dermatologically acceptable base or carrier in which a compound ofe-o-rmula I is stable can be utilized. The preferred compositions for use in this invention are the conventionally cosmetic compositions which can contain a cosmetically active ingredient which is topically administered to human skin to provide a cosmetic effect.
Among the conventional cosmetically active materials which can be utilized in this composition are included: sunscreens, penetration enhancers, moisturizers, surfactants, emollients, colorants, conditioners, bacteriocides, astringents, detergents, etc.
(3 0 The topi i desired cont sunscreen ag formulations utilized in 7 cal compositions of this invention can, if ain suitable sunscreen agents. Any conventional ent can be utilized in formulating the containing compounds of formula I which can be accordance with this invention.
I
These topical compositions which contain compounds of formula I can contain any of the conventional excipients and additives commonly used in preVpring topical compositions.
Among the conventional additives or excipients, which can be utilized in preparing these cosmetic compositions in accordance with this invention are preservatives, thickeners, perfumes and the like. In addition, t'e conventional antioxidants, such as butylated hydroxyanisoles (BHA), ascorbyl palmitate, propyl gallate, citric acid butylated hydroxy toluene (BHT), ethoxyquin, tocopherol, and the like can be incorporated into these compositions. These topical compositions can contain conventional acceptable carriers for topical applications which are generally utilized in these compositions. These compositions may contain thickening agents, humectants, emulsifying agents and viscosity stabilizers, such as those generally utilized. In addition, these compositions can contain flavoring agents, colorants, and perfume which are conventional in preparing cosmetic compositions.
The topical compositions containing compounds of formula I can be applied to the skin and should be preferably applied to the skin at least once a day for at least 2 or 3 times a week. For obtaining the reversal of the elastosis so as to impart tz the skin a smooth and younger appearance the topical compositions should be preferably applied for a oV period of at least five months. After that compositions which contain compounds of formula I should be applied continually to maintain the effect of younger and smoother o" skin. These preparations can be applied according to the need of the patient as determined by the prescribing 4 4 4 ta i 8 physician. In any event, the particular regiment for application of this composition to a patient will typically depend on the age, weight and skin condition of the individual.
The invention is further illustrated in the following examples. These examples are for illustration and are not limitative of the claimed invention.
Example 1 Repair of UVB-Induced Dermal Damage in the Hairless Mouse by Compounds of Formula I Hairless mice (HRS/J strain, Jackson 'abs, 5-7 weeks old at the start of the experiments) were irradiated three times per week with a bank of 8 Westinghouse Sunlamps (FS40) placed about 20cm above the animals. The radiation dose was controlled by an International Light Model IL844A Phototherapy Exposure Control and a detector. The UVB dosing schedule was such that individual doses, seldom exceeding 2 0.06J/cm caused minimal erythema but no burning or scarring. There was significant elastosis, detected by histology, after a total dose of about 3.5J/cm this was confirmed in measurements of elastin in whole skin by means of a radioimmunoassay for desmosine. Demosine is found in elastin hydrolysates and is derived from crosslinks in the elastin molecule; it is a reliable index of total elastin.
Typically, desmosine increased by about 2-3 fold after 3.5J/cm of UVB irradiation. To effect repair of the dermal damage, the UVB irradiation was discontinued and animals were treated three times per week with various concentrations of the compounds of formula I dissolved in acetone. Solutions were made up freshly every week at concentrations such that the dose was delivered in l00,1 2 acetone and applied topically to an ajea of about 10 cm on the back of the animal with a plastic pipette; a control 9 group treated with acetone alone was also included.
After 10 weeks of treatment the animals were sacrificed, skin samples were taken and processed by stancdrd methods. A six micron section from each animal was stained for elastin with Luna's stain and the degree of repair measured quantitatively. In this model, repair is defined by the appearance of a normalized dermis extending from the epidermis down to the layer of compressed elastin. The extent of repair was reflected by the width of this zone. In these studies, the area of the zone on a standard length of histological section was measured by an image analyzer and 2 the results are given as total area in mm per twenty microscopic fields. Data was analyzed by Student's t-test, The results are given in Table I. In Table I, and Table II each group dosed at a particular concentration of compound of formula I contained six to ten animals.
Si teb
-A
I.
10 Table I Group Repair zone. mm 2 Control O.2v Lg of Compound A 0.6 2 6 0.005 0.013 0. 019 0.029 0 .007 0.010 Group +1- +1- +1- +1- +1- 0. 001 0.002* 0.005* 0. 008* 0.002 0.003 Control 0.1llig of compound B 0.3 3 0.003 0.011 0.014 0.021 0.022 0.011 0.001 0,003 0.003 0.005* 0. 004 0.005 P 0.005, P 0.01. P 0.001 vs Control Group Repatr zone, mlf 2 Control 0.l1- g of Compound C 1 2 10 0.005 /-0.001 0.017 +-0.007 0.021 +-0,005* 0.027 /-0.005** 0.028 +1.0.003*** 0.014 +-0.005 P 0.5 P 0.011, P 0.001 vs Control Group Control 0. llig of Comipound D 2 Repair Zone, mm 2 0.005 0,001 0.022 +-0.007 0.033 +-0,007 0.0231- 0.004 0,033 ./-0.005 0 .0 00 0 0 CO 00 0 00 CO 0 P QQ5* p 0.001 vs Control Throughout the specification, Compound A is methyl p-[2-(5,6.7.8-tetra1ydro -5 i5. 8 ,8 te trarnethyl-2 -naphthyl) propenyl Iphenylsulfone: P I i I t -T 1 -L-illl~----ILI ~I_ 11 Compound B is ethyl 9,.7,8-tetrahydro -5,5,8,8-tetramethyl-2-naphthl,,,-propenyl]phenylsulfone; Compound C is methyl p-[2-(5,6,7,8-tetrahydro -5,5,8,8-tetramethyl-2-naphthyl)-propenyl]phenylsulfoxide; and Compound D is ethyl p-[2-(5,6.7,8-tetcahydro -5.5,8,8-tetramethyl-2-naphthyl)propenyl]phenylsulfide.
Example 2 Effect of Compounds of Formula I on the Wrinkles Produced in Hairless Mice by UVB-Irradiation Doses of UVB-i Ladiation sufficient to induce uermal damage in hairless mice were found to cause the appearance of wrinkles on the exposed skin. One skin replica for each animal was taken of these areas using a liquid dental impression material (SILFLO Flexico Developments Ltd., England). Wrinkles appeared in these impressions as ridges which cast a shadow when illuminated with low angle light. A characteristic of the wrinkling pattern was the occurrence of the ridges in a regularly-spaced array about 2-mm apart. The extent of wrinkling was visually assessed using this line pattern and assigned a value (Wrinkle Index) of zero to 4 with zero representing complete effacement of winkling and 4 representing the maximum degree of wrinkiiai. 't was observed that compounds of formula I caused a dose-dependent effacement of the wrinkles with ED values in the Smicrogram range. The results are shown in the following Table.
O 00 0 O a4 1 represents lower-alkyl, lower-alkenyl, lower-alkynyl lower-alkoxy-lower-alkyl, lower-alkanoyl-lower-alkyl, hydroxy- lower -a Ikyl, /2 I) 12 Table II Grou Control 0. 2jig of Compound A 2 6 Wrinkle Index 1.6 +-0.3 0.7 +1 .Q3* 0.6 0.5 0.2 Group Control 0. llig of Compound B 0.3 3 If 1.3 +-0.2 1.3 +-0.3 0.7 -02* 0.3 0.2 *P 0.05, P 0.01, P 0.001 vs Control GroupWrinkle Index Control 0. lig of Compo'3nd C 2 i 1 1.6 +-0.3 0.6 0.3 0.7 +-0.4 0.2 0.4 *P 0.05, P 0.01, P 0.00, vs; Control Creams and gels containing ingredients within the proportions set forth in Examples 3 thr~ugh 7 below can be formulated by conventional means.
0 0 0 0 0 4 13 EXAMPLE 3.
CREAM
w/w A compound of formula I Cetyl Alcohol Stearyl Alcohol Span 60 (Sorbitan Stearate) Mineral Oil Arlacel 165 (Glyceryl/PEG 100 Stearate) Twoen 60 (Polysorbate Miglyol 818 (Caprylic/Capric/Linoleic triglyceride) Sorbitol Solution Disodium Edetate BR-A (Butylated Hydroxyanisole) Methylparaben Propylpar,,ben water q.s.
0.00001-1. 3 2. 0.1 0.05 0.18B 0.05 100.00 o 0 00 0 00 00 0 O 0 0 04 0 oO 00 4 o 4~ 4044 4 4 04 4 4 040~~t 4 4 1- ASC 49 ~.pmu.umq~
I)
I.)
14 EXAMPLE 4.,
CREAM
w/W A Compound of Formul~a I Cetyl Alcohol Arlacel 165 (Glyceryl/PEG 100 Stearate) Miglyol 818 (Caprylic/Capr.c/Lifloleic triglyceride) Sorbitol Solution Disodium Edetate Carbopcnl 934P (Carbomer 931P) BRA (Butylated Hydroxyanisole) Mettiylparabel Propylparaben Sodiumn Hydroxide (10t solution)' Distilled water,~ q.f 0.00001-1.0 5.25-8.75 3.75-6 11.25-18.75 3 .75-6.25 .075-0.125 0.15-0.25 0.0375-0.0625 0.135-0.225 0.0375-0.0625 0,15-0.25 100 .00 &o~ 00 0 4 4 1 44 1 444, L1 o 1 la EXAMPLE w/w A Compound of Formula I Cutina MD (Glyceryl Stearate) Ceteareth-12 Cetyl Alcohol Generol 122E-10 (Ethoxylated Soya Sterol) Cetiol LC (Oleic Acid Decyl Ester) BR-A (Butylated Hydroxyanisole) Sorbitol Solution Disodium Edetate Methylparaben Propylparaben Distilled Water, q.s.
0.00001-1.0 4.5-7.5 3.0-5.0 3.0-5.0 2. 25-3.75 7. 5-12.5 0.0375-0.0625 3.75-6.25 0. 075-0.1325 0.1l35-0.225 0.0375-0.0625 100. 00 0 1 0 4) 4, o 0 0 o 0 0 0 o ~o 0 a0 4)4)4) 0 4)4 4)4) 4, 04404)4)4 4 4, 0~04 0 00 00 0 018800 I I I~ I Ijj q~ 16 EXAMPLE 6.
CREAM
w/w A compound of f ormula I Arlatone 983 (PEG 30/Glyceryl Stearate) Cetyl Alcohol Stearic Acid Neobee oil (Medium chain-length triglyceride) Propylene Glycol 2-phenoxyethanol It Distilled Water, q.s 0.00001-1.0 17.0 100.00 EXAMPLE~ 7.
GEL
w/w 0 ta 00 o t 0 0 001 0 0 A compound of formula I Pluronic L 101 (Poloxamer 331) Aerosil 200 (Silica) PCL Liquid (Fatty Acid Esters) Cetiol V (Decyl Oleate) Neobee oil (Medium chain-length triglyceride) 30 Euhanol G (Octyldodecanol). q.s.
0.00001-1.0 10.00 8 .00 15.00 20.00 15.00 100.00 Creams of Example 3, wherein Compound I is present in weight/weight of 0.0001, 0.001. 0.03, 0.01, 0.1 and 0.3 were made and are preferred.
4I( tt t r. slry Lu.cuaea salrs or suitonic acids and sulfinic acids of compounds of formula I. Any conventional pharmaceutically acceptable base salt of sulfonic or I i -1 17 A cream of Example 6 and a gel of Example 7 were made wherein Compound I is present in weight/weight of It is understood that the proportions of excipients in of Examples 3 and 6, and the gels of Example 7 can be varied, if desired, to change the physical properties of the resulting creams and gels.
i 4 4, 44 4 44 0 44 45 44 44 4 44 44 4 C 44 441 C1
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8699287A | 1987-08-19 | 1987-08-19 | |
US086992 | 1987-08-19 |
Publications (2)
Publication Number | Publication Date |
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AU2118488A AU2118488A (en) | 1989-02-23 |
AU610632B2 true AU610632B2 (en) | 1991-05-23 |
Family
ID=22202176
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU21184/88A Ceased AU610632B2 (en) | 1987-08-19 | 1988-08-19 | Improvements in or relating to methods of treating damaged skin |
Country Status (12)
Country | Link |
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EP (1) | EP0303915B1 (en) |
JP (1) | JPH0627063B2 (en) |
KR (1) | KR890003369A (en) |
AT (1) | ATE89723T1 (en) |
AU (1) | AU610632B2 (en) |
CA (1) | CA1329553C (en) |
DE (1) | DE3881299D1 (en) |
HU (1) | HU203195B (en) |
IE (1) | IE62691B1 (en) |
IL (1) | IL87488A0 (en) |
PH (1) | PH24867A (en) |
ZA (1) | ZA885192B (en) |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5264578A (en) * | 1987-03-20 | 1993-11-23 | Allergan, Inc. | Disubstituted acetylenes bearing heterobicyclic groups and heteroaromatic or phenyl groups having retinoid like activity |
US5602130A (en) * | 1987-03-20 | 1997-02-11 | Allergan | Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity |
US5272156A (en) * | 1989-09-19 | 1993-12-21 | Allergan, Inc. | Acetylenes disubstituted with a heteroaromatic group and a 2-substituted 1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity |
US5183827A (en) * | 1989-09-19 | 1993-02-02 | Allergan, Inc. | Acetylenes disubstituted with a heteroaromatic group and a 2-substituted chromanyl, thiochromanyl or 1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity |
US5264456A (en) * | 1989-12-29 | 1993-11-23 | Allergan, Inc. | Acetylenes disubstituted with a furyl group and a substituted phenyl group having retinoid like activity |
US5324840A (en) | 1992-06-11 | 1994-06-28 | Allergan, Inc. | Method of treatment with compounds having retinoid-like activity and reduced skin toxicity and lacking teratogenic effects |
CH686285A5 (en) * | 1992-08-06 | 1996-02-29 | Beiersdorf Ag | Cosmetic or pharmaceutical preparation used to delay the aging of human skin. |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU548060B2 (en) * | 1981-02-13 | 1985-11-21 | F. Hoffmann-La Roche Ag | Alkyl-aryl sulphur-containing compounds |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CS235526B2 (en) * | 1981-02-13 | 1985-05-15 | Hoffmann La Roche | Method of tetrahydronaphtalene and indane new derivatives production |
US4603146A (en) * | 1984-05-16 | 1986-07-29 | Kligman Albert M | Methods for retarding the effects of aging of the skin |
JP2606711B2 (en) * | 1986-07-16 | 1997-05-07 | エム. クリグマン,アルバート | Method of treating sun-damaged human skin with retinoids |
US4889847A (en) * | 1986-11-03 | 1989-12-26 | Ortho Pharmaceutical Corporation | Prevention of glucocorticoid-induced skin atrophy |
-
1988
- 1988-07-18 ZA ZA885192A patent/ZA885192B/en unknown
- 1988-08-05 DE DE8888112801T patent/DE3881299D1/en not_active Expired - Fee Related
- 1988-08-05 EP EP88112801A patent/EP0303915B1/en not_active Expired - Lifetime
- 1988-08-05 AT AT88112801T patent/ATE89723T1/en not_active IP Right Cessation
- 1988-08-17 HU HU884372A patent/HU203195B/en not_active IP Right Cessation
- 1988-08-17 CA CA000574958A patent/CA1329553C/en not_active Expired - Fee Related
- 1988-08-17 KR KR1019880010430A patent/KR890003369A/en not_active Application Discontinuation
- 1988-08-18 JP JP63203952A patent/JPH0627063B2/en not_active Expired - Lifetime
- 1988-08-18 IL IL87488A patent/IL87488A0/en not_active IP Right Cessation
- 1988-08-18 IE IE252388A patent/IE62691B1/en not_active IP Right Cessation
- 1988-08-18 PH PH37425A patent/PH24867A/en unknown
- 1988-08-19 AU AU21184/88A patent/AU610632B2/en not_active Ceased
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU548060B2 (en) * | 1981-02-13 | 1985-11-21 | F. Hoffmann-La Roche Ag | Alkyl-aryl sulphur-containing compounds |
Also Published As
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ATE89723T1 (en) | 1993-06-15 |
ZA885192B (en) | 1989-04-26 |
EP0303915A2 (en) | 1989-02-22 |
KR890003369A (en) | 1989-04-14 |
IL87488A0 (en) | 1989-01-31 |
IE62691B1 (en) | 1995-02-22 |
CA1329553C (en) | 1994-05-17 |
IE882523L (en) | 1989-02-19 |
HUT48116A (en) | 1989-05-29 |
HU203195B (en) | 1991-06-28 |
JPH0627063B2 (en) | 1994-04-13 |
EP0303915A3 (en) | 1990-08-08 |
JPS6470457A (en) | 1989-03-15 |
AU2118488A (en) | 1989-02-23 |
EP0303915B1 (en) | 1993-05-26 |
DE3881299D1 (en) | 1993-07-01 |
PH24867A (en) | 1990-12-26 |
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