JPS608222A - Anthralin stabilizing composition and method - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compositions and methods for stabilizing anthralin.

Anthralin, also known as dithranol, can cause damage to the skin that appears as small lesions or affects many parts of the body.
'． :i! It is a component of a preparation for the transdermal treatment of dermatological disorders characterized by dryness, redness, and silvery scales.

In recent years, dermatologists have used many new methods to treat psoriasis, but the vast majority of therapeutic agents used have proven ineffective. For example, tar is used to treat psoriasis.
A wide range of topical drugs are used, such as tar derivatives, anthralin, mercury compounds, corticosteroids and keratolytic agents.

Anthralin remains the drug of choice for skin doctors in the treatment of psoriasis. Generally, anthralin is used as the "mainstream" drug in most hospital outpatient treatments. For this purpose, anthralin is generally used in concentrations of 0.05 to 5% by weight, based on the total composition. Hereinafter, unless otherwise specified, percentages are based on the total weight of the composition. Fij means %. When used correctly, anthralin is highly effective and its use is associated with few or no side effects.

Although anthralin is generally acknowledged to be very effective in treating psoriasis, it still has eight major drawbacks: instability, staining of skin and clothing, and skin irritation. Anthralin undergoes photocatalytic oxidation, dimerization reaction and/or chemical decomposition to form 1,8-dihydroxy-anthraquino/and le J l',B/-tetrahydroxy-10,10'-dianthrone and other By-products are produced.

Anthralin is said to be susceptible to autooxidative degradation (ie, free radical oxidation). Its degradation products are believed to be inactive in psoriasis chemotherapy. It is believed that skin irritation and anthrali/erythema are caused primarily by the initial free radical intermediate of anthralin. Anthralin skin blemishes are caused by its oxidation products, i.e. 1,8-dihydroxyanthraquinone or dianthralin. It is believed that this is caused by.

Various solutions to the problem of anthralin stability have been reported, but none of them are satisfactory. Typical conventional solutions are U.S. Pat.
Published in No. 2 8 7.2 1 4. US Pat. No. 4,208,969 discloses the use of a water-soluble oil-insoluble acid antioxidant or a mixture of an acid and a water-soluble oil-insoluble antioxidant in the continuous aqueous phase of an ointment. US Patent No. 4
, 2 8 7, 2 1 4 is ascorbic acid, BHA
Antioxidants such as (butylated hydroxyanisole) and EHT (butylated hydroxytoluene) and other chemicals such as salicylic acid do not stabilize anthralin well, but some alpha hydroxy acids do. ing. Arch, Derm of Ponsuwels and Halsebots.

Forsch, 249.141-152 (1974)
has announced Lactacide pH 2 ■ Soft Kidney containing anthralin. Table 1 of that document shows the instability of the preparations as analyzed by UV spectroscopy and thin layer chromatography. Caron and Schrute J, Parm,
Sci, 70: 11°1205-1207 (
(1981) discloses salicylic acid in a composition containing 0.44 thianthralin, cetyl alcohol, sodium lauryl sulfate, paraffin and petrolatum, but it is not explicitly announced that the composition actually contains water or for the treatment of xerosis. &h9. Can be used to create stable compositions containing water and anthralin at effective concentrations. No anthralin stabilizing effect was observed depending on the chemical composition or concentration range.

Caron et al., J. Pharm. Sci, 70:
11.1205 (1981) or Pha
rmtxcopeial ForqcmMay-June, 19
56-1957 (1982): The U, S.

Pharmcopeial Convention I
U, which is commonly used for stability measurements using the method described in nc,
When anthralin stability was measured by high-pressure liquid chromatography using it instead of S. Pharmacopeia (USP), it was found that the conventional method of anthralin stabilization was generally less stable and less complete than previously thought. It was. While the USP method is not satisfactory for determining anthralin stability, H
The PLC method is the sensitive and reproducible method of choice for determining anthralin stability. The recent literature cited thus far raises serious doubts as to whether the USP or British Pharmacopoeia (BP) method is actually an anthralin stability indicator. U
SP and BP present 11 analytical methods for all anthralin-containing preparations.
It is expected that the PLC method will be changed soon.

In most commercial applications, concentrations of anthralin greater than 0.5 F are rarely, if ever, commercially available for outpatient use, as the composition is subject to rapid loss of anthralin activity and oxidation. If more than 20 inches of the body surface area is affected by patchy psoriasis, the patient should be admitted to the hospital for rapid treatment while preventing irritation of normal skin from contact with high-W anthralin preparations and regulating product stability. One of the major disadvantages of low concentration formulations, ie, about 0.5% or less, is that rapid treatment is not possible with high concentration anthralin formulations.

The evidence presented in the prior art is that alpha, alpha noaraline is susceptible to autoxidative degradation (free radical oxidation) and its degradation products are inactive in fresh chemotherapy.

b. Skin irritation or anthralin erythema is mostly due to the physiologically active initial release of anthralin h11. Occurs due to base intermediates.

C. Contamination of skin and clothing with anthralin causes its coloration 2
oxidation products thereof such as 1,8-dihydroxyanthraquinone.

Conventional methods of stabilizing against anthraphosphorylation include conventional preventive methods such as ascorbic acid, BHA, EHT, EDT.
A (ethylenediaminetetraacetic acid), <use of citric acid, pH
adjustment to an acidic pH, lowering the operating temperature, peroxide removal and light shielding. However, all of the above methods of anthralin stabilization were inadequate.

As noted above, it is clear that anthralin degradation products or initial free radical intermediates create irritation and contamination problems that were heretofore thought to be an unavoidable concomitant of anthralin therapy. If anthralin stability were improved, the irritation and pollution problems indirectly caused by anthralin degradation products would be solved at the same time.

Even if new formulations of anthralin products are developed with better tolerance, more convenience, and less discoloration, anthralin stability in the formulation as indicated by activity loss and discoloration from light yellow to brownish black. The problem still remains unresolved. Anthralin formulations that preserve the long-term stability of anthralin itself and the physical stability of RVRS compounds with good appearance and color have not yet been created. It is well known that commercially available anthralin products undergo rapid discoloration, presenting a very undesirable appearance to the end user.

An acid-stable water-soluble anion in an amount sufficient to stabilize the anthralin in a composition now consisting of water, anthralin and an oil-soluble antioxidant and optionally a water-soluble oxidizing agent in the aqueous phase and having a pH of 5.3 or less. It has been discovered that the addition of ionic surfactants provides the desired stabilization of anthralin in compositions suitable for topical xerotic use. The presence of water-soluble antioxidants in the aqueous phase is disclosed in U.S. Patent No. 4,208;
Contrary to what No. 969 states, it has been found that the long-term stability of anthralin in the formulations of the present invention is not significant. Although it is not a mold cost, the presence of a water-soluble antioxidant may be desirable.

The anthralin concentration used in the present invention may be up to about 5.0 weight. From about 0.1 to about 8.0% by weight of anthralin in compositions suitable for topical use, preferably from about 0.5 to 2%.
．． A usage amount of 0% by weight is preferred.

Of course, higher concentrations of anthralin can also be stabilized by the method of the present invention, but the use of such compositions requires care to prevent irritation to normal skin healing.

Anionic surfactants are used in amounts sufficient to stabilize anthralin. The anionic surfactant may be used in an amount of 0.05 to 10% by weight, preferably 0.1 to 5.0% by weight, and most preferably 0.8 to 1.0% by weight.

Although it is known from the prior art that andralin is more stable at acidic pBs and that the pB of anthralin-containing compositions can be adjusted by the use of dermatologically preferred acids, the use of derivatives such as citric acid or salicylic acid is preferred. The pH of the lauan-containing composition comprising an acid-stable water-soluble anionic surfactant according to the present invention is 5.3 and below.

It is better to use lower pli; the limiting factor is skin irritation. A pH below 4.0 is preferred for use, with a better pB below 3.4.

The present invention provides anthralin products with long-term anthralin stability, cosmetic elegance, better patient tolerance and virtually no discoloration upon packaging storage. It is fully usable for both low-intensity long-term outpatient treatment and high-intensity short-term inpatient treatment of dry j. moss.

It is hypothesized that the present invention will work because oil particles or droplets dispersed in a liquid medium can be charged in one of two ways. 1st
The method is the reactive adsorption of specific ions in solution. In the case of water it is hydronium or hydroxyl ions. The majority of oil particles or droplets dispersed in an aqueous medium become negatively charged by selective adsorption of hydroxyl ions. The charge on the oil particles or droplets that results from the ionization of functional groups such as phosphate, carboxylate, sulfate and sulfonate groups.

Molecules and ions that are adsorbed at a surface or interface are called surfactants. Another expression is αmphip
hi le), which suggests that a molecule or ion has a certain affinity for both polar and non-polar solvents.

It may be liquid-gas or liquid-liquid, but it is the amphiphilic nature of bottom-active molecules or ions that are adsorbed at the interface.

The chemical structure of anthralin is shown below.

Anthralin is an amphiphilic molecule. In other words, anthralin has a certain affinity for both polar and non-polar groups. The amphiphilic nature of the anthralin molecule also makes it concentrated at surfaces or interfaces where the molecule is easily attacked. Under these conditions, mild oxidation initiators of oxygen, hydrogen ions, or metal ions readily attack anthralin and/or promote its decomposition by free radical autoxidation. High surface or interfacial concentrations of anthralin molecules also promote dimer formation through intramolecular interactions.

The present invention provides oil particles, droplets, or It is hypothesized that it produces micelles. The negatively charged surface is a monofunctional group of anionic m1 activator, such as sulfonate, sulfate, phosphate, carboxylate.

Anionic groups of acid-stable surfactants form 2 at the oil-water interface.
The oil particles, droplets or micelles that are adsorbed onto the surface provide a negatively charged surface. The cations in the aqueous phase are attracted to the negatively charged cloth tfi+, and the optical surface also repels any anions such as hydroxyls in the solution once the initial adsorption is complete. In addition to this electrical force, thermal motion tends to distribute all the ions in the solution evenly. As a result, an equilibrium state is established and the system as a whole is electrically neutral.

The distribution ratio of anthralin between oil and water is approximately 5 for the oil phase.
The ratio is approximately 1:000 to 10,000:1. Therefore, in oil-in-water emulsion-based formulations, such as creams, gels, etc. or emulsifying ointments, the two anthralin molecules are dissolved in and, in fact, retained in the oil phase. Once the initial adult phase at the surface is completed, the optical surface area is filled with anions and/or
occupied by nonionic surfactant molecules. The anthralin molecule is not concentrated in the sixth pass and is well protected from the access of other decomposition initiators by the hydroxide ions or the negatively charged surface.

This state is illustrated in FIG. In FIG. 1, the anthralin molecules are in the oil phase and the line αα' is the surface of the particle, oil droplet or micelle. The adsorbed ions that give the surface a negative charge are called potential-determining ions and come from anionic surfactants. Immediately adjacent to this surface layer, there is a region where molecules of the continuous aqueous phase are tightly bound together with a few positive ions, and mainly hydronium ions are tightly bound to the surface. The limits of this region are given by line bb'. The potential at line bb' is still negative, but there are fewer cations than in the bonded negative layer. There are excessive negative ions in the Hid area surrounded by lines bb' and cc'. Gland CC'
Outside of this, the ion distribution is uniform and 1n gas neutrality is observed. fat dd' indicates the outer limit.

The anionic surfactant used as a stimulant in anthralin compositions according to the present invention significantly increases the effeminacy of anthralin. The anionic surfactant protects the anthralin molecule from aggressive forces by separating the negatively charged XIJIIk or edge surfaces that form micelles.

If an anionic surfactant is used in an anthralin-stabilizing amount, the above three points of the present invention can be changed, but stabilization can be achieved by using the antioxidant that has been used in anthralin-poor compositions in the past. can be further ditto.

The acid-stable water-soluble anionic surfactants used in the present invention are readily available compounds such as alkyl phosphates, alkyl sulfonates, alkylbenzene sulfonates, alpha sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, etc. The surfactant is selected from O-like 1r non-toxic surfactants such as ester, inthionate, alkyl ether sulfate, and methyl sarcosine. n) IJ umlauryl sulfate, sodium octoxynol 3-sulfonate, sodium dodecylbenzene sulfonate, sodium lauryl sulfonate, DEA oletho 3-phosphate, sodium diotathylsulfosatasinate, sodium cosylthionate, sodium lauretosulfonate ate and sodium lauryl sarcosinate and the like are preferably used. Mixtures of these surfactants can also be used.

Contrary to the conventional wisdom, antioxidants can also be added to provide long-term stability without the uninvented ffi compound acid bath antioxidants or to improve results.

It has further been discovered that anthralin stability is significantly improved when the anionic Table 1 of the present invention is used in combination with an oil bath antioxidant. Typical antioxidants include ascorbyl palmitate, haduroquinone, propyl galleyate, nordihydroguaiaretic,
BHT.

BIJA1 alpha tecopherol, phenyl alpha naphthylamine 3 and lecithin. It has also been found that bathing antioxidants can be used additionally in the aqueous phase.

Typical antioxidants include sodium sulfite, sodium metabisulfide, sodium bisulfate, sodium bisulfate, sodium formaldehyde, sulfoxylate, acetone sodium metabisulfide, ascorbic acid, and inascorbic acid. , thioglycerol, thiolbitol, thiourea, thioglycolic acid, and cysteine hydrochloride.

The anionic surface-active agents of the present invention may also include non-ionic blush-active agents such as polyalkoxy ethers, polyalkoxy esters, polyalkoxyamides, fatty acid esters of polyhydric alcohols and fatty alcohols. These minimize the potential for skin irritation caused by anions. If desired, anionic surfactants may also include methylcellulose, tragacanth, sodium alginate,
Carpobol 934 (CTFA), bentonite, carboxymethylcellulose 2 and Vcom (CTFA)
) can be used in combination with a compatible softening agent. <C'l'F'A) used above and elsewhere in this specification means CTF
This indicates that the name is taken from the A Cosmetic Ingredient Dictionary (3rd edition, CTFA Association).

Due to the poor stability of anthralin in conventional skin dander chemical compositions, anthralin-containing compositions with anthralin concentrations exceeding 0.5 C by weight are rarely, if ever, on the market.

As a result of the improved anthralin stability afforded by the invention, it is now possible to provide a very stable formulation both in terms of anthralin concentration and physical stability of the formulation in the eye, which is highly effective for the topical treatment of psoriasis. This i-circular strip has an anthralin enrichment of 0.1 to 5.0% by weight or more, and is convenient for outpatient treatment of dry skin. Accelerated high temperature storage stability studies and Arrhenius plots of the data have been conducted on formulations such as Stability V11. It made it possible to embody both stability and physical properties. Maintaining anthralin concentrations below 90% was deemed unacceptable for the purposes of this study.

In order to demonstrate the stability of the anthralin-containing product of the present invention, a gel composition containing gold anthralin in an IM amount (plus 0.05% by weight excess) was prepared from the basic gel composition shown in Example 1 below. The gel compositions were all the same except that the surfactants used were different according to the base gel composition. In addition to gel compositions made using the acid-stable, water-soluble anionic surfactants of the present invention, the product anionic amine surfactant Richamate 1655 from Richton Co., Ltd., and the acid-labile water-soluble anionic surfactants of the present invention, Gel compositions were made using the ionic surfactant triethanolamine stearate to demonstrate the lack of stability of anthralin in gels containing this glaze surfactant.

Samples were tested after storage at room temperature, 35°C and 45°C.

Example L Part A Coal Oil <USP) l 64. V Propyl gallate 0.5 g BilT 2.0 g Salicylic acid 2.0, @O Vtsu) -2 (C1'FA) 6 U, Og I7
ry)-20(CTFA) 200.01i ascorbyl palmitate 1. og Anthralin 10.5.9 Part B PEG-8 (CTFAl 50.0.!/Nlubitol 70% solution 20.0 pEDl'A 1.0 g Sodium bisulfide i, o g Ascorbic acid 10.1 Surfactant 5. 0!J +i'# Add ice making (USP) to make 1000.0.

The composition was prepared by mixing the Part A components and heating the mixture to a temperature of 90°C. Stir until all solids are mixed. The components of Part B were mixed in a separate vessel, heated to 90°C, and stirred to melt the entire surface. Part B was added to part A and mixed. The mixture was stirred at a temperature of 90° C. for 10 minutes, cooled to packaging temperature, and packaged under inert gas in an aluminum tube lined to prevent reaction with the product.

EXAMPLE 1 The base gel composition of Example 1 was used with high surfactant concentrations to demonstrate the upper limit of the use of the acid-resistant water-soluble anionic surfactants of the present invention. Even higher concentrations are possible, but skin stimulation is a limiting factor. The test results are shown in Table ■ below.

Example 2 A satisfactory gel composition was prepared from the following formulation.

Part A Anthralin (1.15g containing 15% excess)
Insetto 20 (C'l'FA) 20.0 (1
Hironyu (USP) 16.0 Olesotho-2 (CTFA) 6.0 Salicylic acid 0.2 Ascorbyl, SU lumitate 0.1 Bill' 0.1 Propyl gallate 0.01 Part B PEG-85,1 Nlubitol 70 % solution 2.0 Ascorbic acid 1.0 Sodium lauryl salt 7ate 0.3 Kuenshun 0.
1 Sodium bisulfide 0.05EDTA O,
01 Purified water (USP) f: Add 100.00.

The components of Part A were mixed and heated to a temperature of 90°C to form a gel.

Stirring was continued until the solids were well mixed. The components of Part B were mixed in a separate container and heated to 90°C to dissolve all the solids. A
Part B was mixed into Part B, and the mixture was continuously stirred for 10 minutes while maintaining the temperature at 90°C. The resulting gel was cooled in a packaging tray and packaged under an inert gas atmosphere in an aluminum tube with a non-reactive lining.

The composition of Example 2 was clinically evaluated. The same composition was used in all cases, but the concentration was varied.

The clinical experiment was conducted by a clinical dermatologist with extensive experience in evaluating drugs used to treat psoriasis.

This rash was observed in patients who received a short treatment of 10 to 20 minutes once a day for 6 weeks with the gel composition of the present invention containing 0.5-2% by weight of anthralin. It shows that it will give good results to the samurai. The patient thus treated had localized dry nails in various places over most of his body surface. 6
The results of the test after a week are shown in Table 1.
This clearly shows the efficacy of the gel.

Table ■ 2% 5 weeks labor 0 1% 1st week 20 Lesions Excellent 10 Dr. Ishi.

2% 5 weeks 10 Only 0.5 1st week 20 Lesion, excellent 10 JJr, E
.

1% 5 weeks 10 only “0.5 part 1 week 20 Lesion Excellent 20 Dr. VIE
Work% 5 weeks 10 Only 1 0.5 1st week 20 Lesion Excellent 11 Dr. B.

1% 5 weeks 10 days only" Appetizer At first, I applied it to the whole body, but the degree of irritation on the normal cortical layer was severe, so I changed it to only the lesion area, and there have been no problems since then.

Nutrition In the table above, ``Good'' indicates a range from slightly clear to fairly clear, and ``Excellent'' indicates a range from fairly clear to completely clear.

It is noteworthy that clinical evaluation of the composition of Example 6 has begun. The composition of Example 2 (water-soluble antioxidant/411k in the aqueous phase) and the composition of Example 6 were used for the short-term treatment of xerolysis.
+IIIIf! Preliminary results do not show any difference as far as the urinary efficacy of i.i. (without water-soluble antioxidants in the aqueous phase) is concerned.

It should be emphasized that the solution of the anthralin stability problem by the present composition of the present invention is of great benefit to the treatment of dry skin as it can be used for short-term treatment.

Example A A ream stand system was prepared using the formulations described in A-F.

Part 4 Vaseline 200.0,? Mineral oil <USPl 50.0 Stearet-2 (C1'FA) 12.5 Stearet-100 (CTFA), 2.5 Anthralin (15
(including % excess) 11.5 Salicylic acid 3.5 Glopyr galley 1- 0.05 BHT O,5 Ascorbyl palmitate 0.5 Part B Sodium lauryl sulfate 1.50. @
Ascorbic acid '2.0 PEG-8<CTFA) 60.0 Dry sodium phosphate 0,75EDTA O,
5 Sorbic acid 0.5 Xanthancomb (USI) 3.25 Purified water (Us
P) to make 500.00.

The ingredients of part A were mixed and heated to a temperature of 70°C to completely mix the solids to form a cream. Mix part B ingredients in a separate container 7
Heat to 0°C to dissolve the solid. Part B was added to 4 parts, and both parts were thoroughly mixed while maintaining the temperature at 70°C. The resulting cream was cooled to packaging temperature and packaged.

Example A satisfactory rod-shaped composition was manufactured by the following formulation.

Synchro Wax l1GL-C45-0! i' (close) Syntalo wax ERL -C15,0 (close) Vaseline 310.0 Coconut oil (USP l l 20.0 Salicylic acid 0.5 Globil gallate 0.05 BHT O,25 Ascorbyl palmitate 0.5 Sodium lauryl sulfate 2.5 ascorbine
Epidemiology 0.25 Anthralin 5.75 Purified water<USPI 4.0 Sodium lauryl sulfate and ascorbic acid were dissolved in water. After the remaining components were mixed at 80°C, the previous solution was added and the temperature was brought to 75°C. The composition was then poured into a mold, cooled and solidified, and packaged.

Example& A satisfactory ointment composition was prepared according to the following formulation.

Cetostearyl alcohol 280.0p White soft paraffin 500.0 Liquid paraffin 200.0 Sodium lauryl sulfate 5.0 Salicylic acid
2.0 Ascorbic Lumiyt i.

EHA, 0.5 EDTA O.05 Ascorbic 9 0.05 Anthralin 11.5 Isei Seishui <USPI 4.00 All components except Anthralin were vigorously mixed with water at 75° C. until foaming ceased. Then, anthralin was added and the mixture was further stirred for 30 minutes. The composition was cooled and packaged at -55°C.

The gel compositions described in Examples 6 and 7 were further prepared by the method described in Example 1. All are extremely stable upon long-term storage.

Example Part A Anthralin 11.551 Incetet-20 (CTFA) 200.0 Olet-2t CTFA) 60.0 Mineral oil <USP) 16
5.0 Glopyr gallate 0.1 BHT 1.0 Salicylic acid 20 Ascorbyl palmy r-toi.

3 parts PEG-8 (CTFA) 50.0.9 Sorbitol 70% solution 20.0 EDTA O,2 Citric acid 5.5 Sodium lauryl sulfate 5.0 Purified water <IH
;P) is set to 1000.0.

Example 7 Part A Anthralin 10.5.9 Incetet-20 (CTFA) 200.0 Oretto 2 kcTFA) 60.0 Copper oil (JSP) 16
0.0 Propyl gallate 0.5 EIIT 2.0 Salicylic acid 2.0 Ascorbyl/s, O lumitate 1. OB Department PEG
-8 (CTFA) 50.09 Sorbitol 70% solution H
20-0 Ascorbic acid 10.0 Sodium bisulfide 1.0 ED1'A 1.0 Sodium lauryl sulfate 5.0 Purified water (US
, P) and set it to 'LOO0,0.

The anthralin composition of the present invention can be prepared and used in the form of cream, gel, ointment, or stick, but cream or gel form is preferred from the viewpoint of ease of use.

Having described the invention in the foregoing specification, reference should be made to the claims that define the scope of the invention.

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing the state of adsorption of a surfactant onto anthralin. Applicant: Bristol-Myers Company - Agent: Patent attorney: Ryoji Kawase □Patent attorney: Takehiko Saito. Procedural amendment (method) July 5, 1980 Director General of the Patent Office Mr. Shiga Aza 1, Indication of the case 1982 Patent Application No. 116766 2 Name of the invention Anthralin stabilizing composition and method 3, Person making the amendment r Relationship to the incident Patent volume I11 Name Pristreux Myers Company Name Patent attorney (6323) Ryoji Yosera'. 5. Subject of amendment ゛・, 2 (1) Column of applicant for patent and section certifying power of attorney (2) Drawing attached to application 6 Contents of amendment Procedural amendment document July 5, 1980 Patent Agency Commissioner Manabu Shiga1, Indication of the case, Patent Application No. 116766 of 1982, Name of the invention, Anthralin stabilized composition and method 3, Relationship with the person making the amendment, Patent applicant name: Pristreux Meyers Company Name: Patent Attorney (6323) Ryoji Yosera. Column 6 of Detailed Description of the Invention in (5, Subject of Amendment - Specification) Contents of Amendment (1) The chemical formula in line 8 on page 18 of the specification is amended as follows. -1″:

Claims (1)

[Scope of Claims] 1. Stabilized anthralin in a pharmaceutically acceptable composition suitable for topical treatment of psoriasis, comprising water, an oil-soluble antioxidant, and anthralin in an amount sufficient to provide a psoriasis therapeutic effect. 1. A composition comprising an acid-stable water-soluble anionic surfactant in an amount sufficient to 2. The composition of claim 1, wherein the surfactant is stable at 72H of about 5.8 and below. 3. The composition of claim 1, wherein the surfactant is stable at a pH of about 4 and below. 4. The composition of claim 1, wherein said surfactant is stable at a pII of about 8-4. 5. The composition of claim 1, wherein said surfactant is stable at a pH of about 8.2. 6. The anthralin content is about 0 based on the total composition weight.
．． A composition according to any one of claims 2 to 5, wherein the surfactant is present in an amount of from about 0.05 to about 10% by weight. . 7. The anthralin content is about 0 based on the total composition weight.
．． 1 to about 8.0% by weight and the surfactant is included in an amount of about 0.1 to about 5.0% by weight. Composition of. 8. The anthralin content is about 0 based on the total composition weight.
．． 5 to about 2.0 inches by weight and the surfactant is present in an amount of about 0.3 to about 1.0 inches by weight. Compositions as described. 9. The anthralin content is about 0 based on the total weight of the composition.
．． 1 to about 3.0% by weight and the surfactants include alkyl sulfates, alkyl sulfonates, alkylbenzene sulfonates, sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, isethionates, alkyl ether sulfates, methyl sarcosine and the like. The yarn material according to any of the claims, which is selected from the group consisting of non-toxic anionic surfactants. 10. The anthralin is present in an amount of about 0.5 to about 2.0 wt-fi% based on the total weight of the composition, and the surfactant is an alkyl sulfate, an alkyl sulfonate, an alkylbenzene sulfonate, a sulfonyl fatty acid, an alkylphos. ate, dioctyl sulfosuccinate, isethionate, alkyl ether sulfate,
A composition according to any one of claims 2 to 5, which is selected from the group consisting of methylsarcosine and similar non-reactive anionic surfactants. 11. The anthralin is contained in an amount of about 0.1 to 5.0% by weight based on the total weight of the composition, and the surfactant is an alkyl sulfate, an alkyl sulfonate, an alkylbenzene sulfonate, a sulfonyl fatty acid, an alkyl phosphate, a dioctyl Sulfosuccinate, isethionate, alkylate sulfate,
Methylsarcosino. J: Selected from the group consisting of non-toxic anionic surfactants according to Hillr J. The composition according to any one of. ν. The anthralin content is about 0 based on the total composition weight.
．． 1 to 3.0% by weight and the surfactants are argyl sulfonate, sulfonate, alkylbenzene sulfonate, sulfonyl fatty acid, alkyl phos 7ate, dioctyl sulfosuccinate, isethionate, alkyl ether sulfate, methyl sarcosine and It is derived from a group consisting of similar non-toxic anionic surfactants and has a Qjff of about 0.1 to 5.
A composition according to any one of claims 2 to 5, wherein the composition is comprised in an amount of 5%. Quick. The anthralin content is about 0 based on the total composition weight.
．． 5 to 2.0 weight @ 'fit and the above surfactants are alkyl sulfates, sulfonates, alkylbenzene sulfonates, sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, isethionates, alkyl ether sulfates, methyl sarcosine and the like. selected from the group consisting of non-toxic anionic surfactants of about 0.3 to 1.07
1Uii-A composition according to any one of claims 2 to 5. 14. The composition according to claim 11, wherein the surfactant is sodium lauryl sulfate. b. 2. The composition of claim 1, wherein said composition is an oil-in-water emulsion, and the emulsion does not contain an oxidizing agent in the aqueous phase. 16. Claim 1, wherein the composition is in solid form.
The composition according to any one of Items 1 to 15. 16. A composition according to any one of claims 1 to 15, wherein the composition is a cream. Claims 1 to 1, wherein the composition is a gel.
The composition according to any of items 5 to 5. Costume. The composition according to any one of claims 1 to 15, wherein the composition is an ointment. Season. 2. The composition of claim 1, wherein the composition is an oil-in-water or water-in-oil liquid, and the oil phase contains an oil-soluble antioxidant in an amount sufficient to improve anthralin stability. 4. Claims in which the composition is an oil-in-water emulsion
Composition according to item M20. Claim 2: The Momme 0 composition comprises a water-soluble antioxidant in an amount sufficient to improve anthralin stability in the aqueous phase.
σ piece 1” acid described in item 0. A composition according to claim 1, wherein the anionic surfactant is a mixture of two or eight or more suitable anionic surfactants. 21. A method for improving the stability of an anthralin-containing composition comprising adding to the anthralin-containing composition an acid-stable water-soluble anionic surfactant in an amount sufficient to stabilize the anthralin. 25. The method of claim 24, further comprising adjusting the pH of the composition to 5.33 or less. 2. When the emulsion has an oil phase, Claim 27 includes an oil-soluble antioxidant added to the composition; Claim 26 includes a water-soluble antioxidant added to the composition. the method of.