Patent Application
20120237597
This invention relates to a method for treating psoriasis.
Psoriasis is a chronic skin disease affecting approximately 2-3% of the world population. Presently, psoriasis is without a permanent cure and its influence on the affected individual's life quality is devastating. People often experience flares and remissions throughout their life. Although new biological-immunological therapies are being developed, the mainstay armamentarium to treat psoriasis systemically includes methotrexate, cyclosporin and oral retinoids. Each treatment has advantages and disadvantages, and what works for one patient may not be effective for another.
Since the 1930s, vitamin A deficiency has been known to cause hyperkeratosis of the skin (phrynoderma) and as early as 1960s synthetic Vitamin A has been used for the treatment of psoriasis, though with low efficacy over toxicity ratio. Further research resulted in the development of the second generation of retinoids, the mono-aromatic retinoids, etretinate and its metabolite acitretin. Etretinate and acitretin are highly effective systemic treatments for psoriasis as well as for disorders of keratinization and for cutaneous lupus. However, despite the demonstrated clinical success of retinoid therapy, this treatment has a significant potential for toxicity, especially elevated liver functions and elevated triglycerides and LDL-Cholesterol and it requires close laboratory supervision. In addition, teratogenicity, the primary side-effect of retinoids, remains a major concern.
There are several forms of psoriasis, and each form has unique characteristics that allow dermatologists to visually identify psoriasis to determine what type, or types, of psoriasis is present. Sometimes a skin biopsy will be performed to confirm the diagnosis. The main types of psoriasis include the following:
Treatment depends on the severity and type of psoriasis. Some psoriasis is so mild that the person is unaware of the condition. A few develop such severe psoriasis that lesions cover most of the body and hospitalization is required. These represent the extremes. Most cases of psoriasis fall somewhere in between.
Psoriasis treatments fall into 3 categories:
Bollag, W. and Ott, F. (1999) Dermatology 199:308-312, describe the treatment of chronic hand eczema with oral 9-cis-retinoic acid. The article states that “Psoriasis . . . did not respond to well-tolerated doses of oral 9-cis-retinoic acid”.
Peter C. M. van de Kerkhof (2006) Dermatologic Therapy 19:252-263, describes the use of Acitretin (SORIATANE®, Roche Pharmaceuticals), a second generation oral systemic retinoid, for the treatment of psoriasis.
In a first aspect, the present invention relates to a method for treating psoriasis in a subject comprising orally administering to the subject a pharmaceutically effective amount of crude Dunaliella powder.
The active ingredient in accordance with the invention is a substantially crude Dunaliella algae preparation, typically dried Dunaliella algae. The term “crude” comes to exclude an extract or purified compound obtained from Dunaliella algae. The Dunaliella algae are preferably Dunaliella bardawil. Other species include D. salina, D. viridis, D. peircei, D. parva, D. media, D. euchlora, D. minuta, D. tertiolecta, D. primolecta, D. acidophila, D. quartolecta and D. polymorpha.
In a preferred embodiment, the substantially crude Dunaliella algae preparation contains β-carotene (BC) at an approximately 1:1 ratio of 9-cis to all-trans isomers of BC or greater than 1:1 ratio of 9-cis to all-trans isomers of BC.
The terms “treating” or “treatment” in the present specification should be understood as bringing about an improvement in the pathological symptoms of the disease, and in some cases curing the disease. The effectiveness of a psoriasis therapeutic treatment of a subject may be assessed at various time points before, during and after the treatment by one or more of the following: Psoriasis Area and Severity Index (PAST); Percentage (%) of skin covered with psoriasis; Dermatology Life Quality Index (DLQI); Patient Global Assessment of Psoriasis Activity and Physician Psoriasis Global Assessment (PGA). The severity of the disease may be determined by various conventional methods such as by pathological techniques.
An “effective amount” should be understood as an amount or dose of the active ingredient which is sufficient to achieve the desired therapeutic effect, i.e. treatment of the indicated diseases. The effective amount depends on various factors including the severity of the disease, the administration regimen, e.g. whether the preparation is given once or several times over a period of time, the physical condition of the subject; etc. The artisan should have no difficulties, by minimal experiments, to determine the effective amount in each case. In one embodiment of the invention, the expected dose range may be 1-6 capsules per day, 300 mg Dunaliella powder per capsule.
The crude Dunaliella powder is preferably administered orally, for example in an encapsulated form. However, other systemic, non-topical forms of administration are contemplated such as Dunaliella powder formulated with pharmaceutically-acceptable excipients for intravenous, intramuscular, intraperitoneal or subcutaneous administration.
In a second aspect of the invention, there is provided a pharmaceutical composition for treating psoriasis in a subject comprising crude Dunaliella powder.
In a third aspect of the invention, there is provided a use of a pharmaceutically effective amount of crude Dunaliella powder for the preparation of a pharmaceutical composition for treating psoriasis in a subject.
In order to understand the invention and to see how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:
All of the human studies described below employed capsules containing Dunaliella powder prepared as follows.
Dunaliella bardawil (hereinafter “Db”) was grown and cultivated in large body open salt water ponds of 50,000 m2 to obtain algae comprising approximately 8% by weight of β-carotene (hereinafter “BC”) at an approximately 1:1 (by weight) ratio of 9-cis and all-trans isomers of BC, or greater than 1:1 ratio of 9-cis and all-trans isomers of BC. The algae were harvested by dislodging centrifuges into a concentrated paste. The paste was washed to remove the salt and sterilized, and then spray dried to yield Db powder comprising approximately 8% BC and less than 5% moisture. The powder was packaged in capsules of 250-300 mg algae containing 15-20 mg of BC each together with all of the natural components of the algae. The BC of the capsules retains the original ratio of isomers. The capsules are packaged in vacuum closed blisters which have a shelf life of up to three years.
Patients and Methods
The study was randomized, double-blind, and vehicle-controlled. Eligible patients were 18 years of age or older with stable, active plaque psoriasis involving 10% body surface area (BSA) or less. Exclusion criteria were: serious or unstable medical or psychological condition, active liver or renal disease, smoking, history of alcohol or drug abuse within the past one year, pregnancy, or planning on becoming pregnant. Concomitant topical therapy, phototherapy or systemic therapy for psoriasis was prohibited throughout the study, with the exception of emollients. Patients, investigators, and all study staff were blinded to treatment assignments.
Patients were randomly assigned into two groups: 22 subjects were treated with Dunaliella capsules and 11 subjects (control) were treated with capsules containing starch powder, as the placebo. Treatment dosage was four capsules of the alga D. bardawil (Nikken Sohonsha Corporation, Gifu, Japan), two capsules after breakfast and two after dinner. Each capsule contained 15-20 mg β-carotene with a ratio of 9-cis β-carotene to all-trans β-carotene of about 1:1.
An institutional review board or ethics committee approved the study protocol. Written informed consent was obtained from patients before the start of any study related procedure.
Clinical Efficacy Evaluation
As a measure of the clinical response, (Psoriasis Area and Severity Index) PASI scores were given by an investigator blinded to the treatment assignment at baseline, after 6 weeks and at completion of the study (12 weeks). As a marker of inflammation, the acute phase protein C-reactive protein (CRP) was measured using a commercial kit by autoanalyzer (Olympus). Digital photographing of the lesions was carried out by the same schedule. A Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate the quality of life of patients at 0, 6 and 12 weeks.
Safety and Tolerability Evaluation
At the pre-study visit, the medical history was recorded and a physical examination, including vital parameters (e.g. blood pressure, pulse, weight, and temperature), was completed. A blood sample was taken for analysis of complete blood cell counts, liver and renal functions, fasting lipid analysis, 9-cis β-carotene, and all-trans β-carotene at baseline and at 6 and 12 weeks.
Nutritional Evaluation
Patients' dietary intakes were assessed by the 24 h recall method delivered by an experienced nurse, directed by a clinical dietitian, on 3 days during the 12 week period, 2 days in the middle of the week and 1 day on the weekend. The data was analyzed for nutrient content by the nutrition data system of the International Center of Health and Nutrition at Ben-Gurion University, Beer-Sheba, Israel.
Statistical Analysis
Paired t-test or Wilkoxon signed ranked test for non-parametric variables were used to compare the results of the human group before and after the Dunaliella administration. Pearson's correlation test was used to detect the link between variables. Statistical tests were all two-sided. P<0.05 was accepted as statistically significant.
Results
Efficacy
33 patients were recruited. 7 patients did not attend treatment sessions regularly or failed to comply with the study requirements and were excluded from evaluation. 26 patients completed the study; of these, 15 had received treatment with Dunaliella and 11 with control, placebo pills. The characteristics of the two patient cohorts are given in Table I. The treatment groups were similar in demographic and disease characteristics at baseline. All participants who completed the trial were at least 85% compliant with the treatment regimen as determined by patient interview and pill counts. The results are summarized in
Dunaliella
After six weeks of twice-daily treatment, PASI scores were significantly reduced from baseline in patient group treated with Dunaliella, whereas the control group did not reach significance (P=0.04 vs. P=0.6, respectively). Similar results were obtained after 12 weeks of treatment (P=0.004 vs. P=0.07, respectively). The number of patients reached PASI 50% after 12 weeks of treatment was 80% in Dunaliella group and 45% in control group. The number of patients reached PASI 75% after 12 weeks of treatment was 40% in Dunaliella group and 27% in control group. In order to evaluate Dunaliella effect on the patient's quality of life, DLQI assay was performed. The results are summarized in
As a surrogate marker for inflammation, CRP levels were analyzed at the baseline and at weeks 6 and 12. Significant reduction in CRP was found in the Dunaliella group but not in the control group.
Thus, the treatment with Dunaliella resulted in a significant improvement in the psoriasis patients.
Safety
There were no treatment-related adverse events in the overall study. In the Dunaliella group, one patient had a myocardial infarction during percutanerous transluminal coronary angioplasty leading to an emergency coronary artery bypass. In the control group, one patient had syncope, without a known cause. Two patients in the Dunaliella group reported accelerated hair growth and darkening of hair.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IL10/01026 | 12/5/2010 | WO | 00 | 5/29/2012 |
| Number | Date | Country | |
|---|---|---|---|
| 61285358 | Dec 2009 | US |
