HK1166263B - Use of a foamable composition essentially free of pharmaceutically active ingredients for the treatment of human skin - Google Patents
Use of a foamable composition essentially free of pharmaceutically active ingredients for the treatment of human skin Download PDFInfo
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- HK1166263B HK1166263B HK12106921.7A HK12106921A HK1166263B HK 1166263 B HK1166263 B HK 1166263B HK 12106921 A HK12106921 A HK 12106921A HK 1166263 B HK1166263 B HK 1166263B
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- dimethyl ether
- stearate
- caprylic
- polysorbate
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Description
Technical Field
This application claims priority from european patent application EP 0802233.2 (filing time: 23/12/2008) and all the benefits of prior U.S. application serial No. 61/140,152 (filing time: 23/12/2008), all of which are incorporated herein by reference, according to the paris convention.
Many foamable compositions containing pharmaceutically active ingredients are known in the art for treating various medical conditions of the skin or body cavity. The prior art includes WO2005/018530, WO2008/038140, US2008/044444, US2006/275218, US2007/020213, US2002/001599, WO2004/037225, WO2005/011567, US2005/0232869, US2005/0069566 and others, all of which are incorporated herein by reference. These foamable compositions and foam carriers were developed because they can contain a number of pharmaceutical ingredients for the treatment of various skin or body cavity diseases. These foams are easy to apply to the skin and avoid stinging and drying-properties that have been reported in previous foam compositions. However, these compositions all require the presence of one or more pharmaceutically active ingredients, such as anti-inflammatory agents (e.g. COX-1 inhibitors, COX-2 inhibitors, salicylic acid derivatives, dicarboxylic acids or dicarboxylic acid derivatives, THF-alpha agents, immunosuppressive agents, immunomodulatory agents, glucocorticoids, steroids or others). It is not necessary to indicate that the need for pharmaceutically active agents is disadvantageous, since these agents may have undesirable side effects on at least some patients.
Summary of The Invention
We have surprisingly found that a foamable composition substantially free of pharmaceutically active ingredients, consisting of:
(a) at least one softening agent, wherein the at least one softening agent,
(b) at least one kind of stabilizing agent is added,
(c) at least one kind of preservative agent is added,
(d) at least one kind of emulsifier, which is selected from the group consisting of,
(e) at least one foam stabilizer,
(f) at least one humectant
A preferred embodiment of the present invention is the use of the above foamable composition substantially free of pharmaceutically active ingredients, together with a propellant, for the treatment of human skin, in particular for the treatment of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis, wherein:
(a) the at least one softening agent is caprylic/capric triglyceride,
(b) at least one stabilizer is cetyl/stearyl alcohol or glyceryl stearate or a mixture thereof,
(c) at least one preservative is a benzoic acid,
(d) at least one emulsifier is PEG-40 stearate, polysorbate 80 or a mixture thereof,
(e) at least one foam stabilizer is methylcellulose, xanthan gum or mixtures thereof,
(f) the at least one humectant is dimethyl isosorbide, propylene glycol, or a mixture thereof.
A particularly preferred embodiment of the present invention is the use of a foamable composition substantially free of pharmaceutically active ingredients as described above, together with a propellant, for the treatment of human skin, in particular for the treatment of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis, said foamable composition comprising:
(a) the caprylic/capric triglyceride is used in an amount of about 10.87 weight percent,
(b) about 1.09 weight percent of a mixture of cetyl/stearyl alcohol and about 0.54 weight percent of glyceryl stearate,
(c) benzoic acid is present in an amount of about 0.1 weight percent of the at least one preservative,
(d) a mixture of about 2.83 weight percent PEG-40 stearate and about 0.98 weight percent polysorbate 80,
(e) a mixture of about 0.11 weight percent methylcellulose and about 0.27 weight percent xanthan gum,
(f) a mixture of about 5.44 weight percent isosorbide dimethyl ether and about 10.87 weight percent propylene glycol.
The compounds which can be used as propellants are gaseous at room temperature and pressure and liquefy after pressurization at room temperature. Useful propellants are butane, propane, isobutylene, dimethyl ether, fluorocarbon gases or mixtures thereof.
The term "pharmaceutically active compound" or "pharmaceutically active ingredient" refers to a compound that is confirmed to have pharmacological activity in clinical trials and is approved as a drug by the european medicines agency (EMEA) or the U.S. Food and Drug Administration (FDA). The term "substantially free of a pharmaceutically active compound" or "substantially free of a pharmaceutically active ingredient" means that no "pharmaceutically active compound" or "pharmaceutically active ingredient" is intended to be added to the composition. Thus, the total amount of pharmaceutically active ingredient due to unintentional contamination is well below 0.05%, preferably below 0.01%. Most preferably, no pharmaceutical ingredient is detectable in the composition by standard analytical methods used in pharmaceutical technology.
Foamable compositions according to the invention are prepared by methods known to those skilled in the art as described in the art. They are typically packaged in containers having outlet valves. Also possible valve inner vessels are well documented in the art and need not be explained herein.
The foamable composition is substantially free of alcohol, i.e., short chain alcohols (having a chain length of 1-4 carbon atoms).
A known disadvantage of the prior art compositions is the low solubility of the pharmaceutically active compound. Thus, the absence of the need to dissolve (solve) any pharmaceutically active compound is an advantage of the composition according to the invention.
Clinical trials have shown that foamable compositions according to the description herein have beneficial properties, especially in the treatment of rosacea. It is very surprising to note that this therapeutic effect can be achieved without the use of any pharmaceutically active ingredient. The composition according to the invention can treat a number of other medical conditions such as acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis and neurodermatitis.
In addition, the compositions described herein may be used for prophylactic treatment of human skin (e.g., for patients with a known tendency to develop the disease).
Foamable compositions according to the description herein may also be used for cosmetic treatment of human skin.
Accordingly, it is another aspect of the present invention to provide a method of treating a skin disorder of a human, such as acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis and neurodermatitis, by topically applying the foam described herein to a patient in need thereof.
Another aspect of the invention is to provide a method for prophylactic treatment of human skin, particularly for humans with a known tendency to develop skin diseases such as acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis and neurodermatitis, by topical application to humans of the foam described herein.
Another aspect of the present invention is to provide a method of cosmetically treating human skin by topically applying the foam described herein to a human.
For all of these applications (therapeutic, prophylactic or cosmetic) described herein, the following compositions substantially free of active pharmaceutical compound packaged in containers having outlet valves were found to be most useful
| 10.00-12.00 g/100g | Caprylic/capric triglyceride |
| 0.90-1.20 g/100g | Spermaceti/stearyl alcohol |
| 0.44-0.70 g/100g | Stearic acid glyceride |
| 0.10-0.15 g/100g | Benzoic acid |
| 2.50-3.00 g/100g | PEG-40 stearate |
| 0.08-0.20 g/100g | Methyl cellulose |
| 0.20-0.32 g/100g | Xanthan gum |
| 0.90-1.20 g/100g | Polysorbate 80 |
| 5.35-6.00 g/100g | Isosorbide dimethyl ether |
| 10.87-12.25 g/100g | Propylene glycol |
| To pH4.5 | Sodium hydroxide |
| To 100 of | Pure water |
| 7.00-9.00 g | Propellant blend |
Examples
Example 1
The following compositions were prepared according to methods known in the art.
The composition according to example 1B showed the best beneficial properties.
Example 2
Patients with rosacea were treated with the composition described in example 1. The specific composition is applied several times a day, preferably at least three times a day. After two weeks of use, the patient showed a significant reduction in rosacea symptoms. After continued use as above for a further period of time, the symptoms further decrease. Especially patients with mild rosacea can benefit from this application.
Example 3
Patients suffering from psoriasis are treated with a composition according to the invention. The composition is applied several times a day, preferably at least three times a day. After two weeks of use, the patients showed a significant reduction in psoriasis symptoms. After continued use as above for a further period of time, the symptoms further decrease.
Example 4
Comparing the application of the composition according to example 1 with what is disclosed in the prior art, the following data are collected. The document US2008/044444 is considered the closest prior art. Example 9 of US2008/044444 discloses a dicarboxylic acid composition comparable to the composition of claim 1, but containing 15% azelaic acid. Azelaic acid is known to be effective in the treatment of rosacea. It is, for example, under the trade name FinaceaAnd Skinoren GelPart of the gel formulation sold and approved by various regulatory agencies, including the FDA. Accordingly, azelaic acid compositions such as Finacea are considered to be useful in the treatment of rosaceaThe standard therapy of (1). US2008/044444 describes a number of diseases that can be treated with the compositions of US2008/044444 (see [ 0186)]Segment). However, there is no specific data demonstrating that such compositions can treat any of the mentioned diseases.
The applicant has carried out a clinical study to compare the composition described herein with the composition described in example 9 of the prior art US 2008/044444. In a 12-week exploratory multicenter double-blind experiment, the foam composition containing azelaic acid according to US2008/044444 example 9 (hereinafter "Aza foam") was compared with a composition according to the present application example 1b without any pharmaceutically active ingredient. More than 80 patients were treated: about 50% use the foam with azelaic acid (Aza foam) and the other 50% use the foam composition according to example 1 b. The patients were treated topically twice daily for 12 weeks. The results are shown in the attached drawings:
figures 1 and 2 show the overall investigator assessment (IGA) score representing the severity of the disease assessed before and after treatment with both compositions. Clinical researchers must score the severity of papulopustular rosacea before and after treatment. Figure 1 shows the IGA fraction of a composition according to the present invention and figure 2 is the IGA fraction of a composition according to US2008/044444 example 9. All data is provided as a percentage of patients treated. Figures 1 and 2 show the comparative efficacy of two compositions: it was found that many patients with moderate to severe papulopustular rosacea became healed to mild before treatment. No statistically significant differences were found in each treatment. This finding is surprising to the skilled person, since azelaic acid is a well known drug and standard therapy in the treatment of rosacea. Thus, it is very surprising that the foamable composition without azelaic acid according to example 1 of the present application shows comparable results.
In addition, the telangiectasia score during the experiment was determined. In the same randomized double-blind experiment, researchers were asked to compare the severity of telangiectasia intensity. At the end of the 12 week period, the investigator evaluated the patient for improved, sustained or worsening telangiectasia. The results are shown in FIG. 3. It was very surprising to note that the number of patients with improved telangiectasia scores was much greater than that treated with the foam containing azelaic acid.
In addition, the number of adverse reactions (e.g., itching, stinging and burning) was counted. Only mild or moderate adverse effects were reported in this clinical study, and no serious adverse effects were reported. As shown in figure 4, the total number of adverse reactions in the prior art composition was significantly higher compared to the composition according to the invention.
Claims (7)
1. Use of a foamable composition substantially free of pharmaceutically active ingredients for the manufacture of a medicament for the treatment or prevention of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis packaged in a container having an outlet valve, or for the manufacture of a cosmetic product packaged in a container having an outlet valve, said foamable composition consisting of:
。
2. Use of a foamable composition substantially free of pharmaceutically active ingredients according to claim 1 for the preparation of a medicament for the treatment or prevention of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis packaged in a container having an outlet valve, or for the preparation of a cosmetic product packaged in a container having an outlet valve, said foamable composition consisting of:
Or consists of:
Or consists of:
Or consists of:
Or consists of:
。
3. Use of a foamable composition substantially free of pharmaceutically active ingredients according to claim 1 for the preparation of a medicament for the treatment or prevention of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis packaged in a container having an outlet valve, or for the preparation of a cosmetic product packaged in a container having an outlet valve, said foamable composition consisting of:
。
4. Use of a foamable composition substantially free of pharmaceutically active ingredients according to any of claims 1 to 3 wherein the propellant is butane, propane, isobutene, dimethyl ether, fluorocarbon gas or mixtures thereof.
5. A container with an outlet valve filled with a foamable composition substantially free of pharmaceutically active ingredients for producing a foam for the treatment or prevention of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis, or for cosmetic treatment of human skin, said foamable composition consisting of:
。
6. A container with an outlet valve filled with a foamable composition substantially free of pharmaceutically active ingredients for producing a foam for the treatment or prevention of rosacea, acne, atopic dermatitis, contact dermatitis, perioral dermatitis, psoriasis or neurodermatitis, or for cosmetic treatment of human skin, said foamable composition consisting of:
Or consists of:
Or consists of:
Or consists of:
Or consists of:
。
7. A container with an outlet valve filled with a foamable composition substantially free of a pharmaceutically active ingredient according to one of claims 5 and 6, wherein the propellant is butane, propane, isobutene, dimethyl ether, fluorocarbon gas or a mixture thereof.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14015208P | 2008-12-23 | 2008-12-23 | |
| EP08022333A EP2210588B1 (en) | 2008-12-23 | 2008-12-23 | Foamable composition essentially free of pharmaceutically active ingredients for the treatment of human skin |
| EP08022333.2 | 2008-12-23 | ||
| US61/140152 | 2008-12-23 | ||
| PCT/EP2009/009350 WO2010072422A1 (en) | 2008-12-23 | 2009-12-22 | Use of a foamable composition essentially free of pharmaceutically active ingredients for the treatment of human skin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1166263A1 HK1166263A1 (en) | 2012-10-26 |
| HK1166263B true HK1166263B (en) | 2014-08-29 |
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