US 200701.96507A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0196507 A1 Majeed et al. (43) Pub. Date: Aug. 23, 2007

(54) COMPOSITIONS AND METHODS Related U.S. Application Data CONTAINING HIGH PURITY FATTY ALCOHOL C24 TO C36 FOR COSMETC (62) Division of application No. 10/604.203, filed on Jul. APPLICATIONS 1, 2003, now Pat. No. 7,217,546. (76) Inventors: Muhammed Majeed, Piscataway, NJ Publication Classification (US); Geetha Kanhangad Gangadharan, Bangalore (IN); (51) Int. Cl. Subbalakshmi Prakash, Piscataway, A6II 35/64 (2006.01) NJ (US) (52) U.S. Cl...... 424/539 Correspondence Address: SABINSA CORPORATION 7O ETHEL ROAD WEST (57) ABSTRACT UNIT 6 PISCATAWAY, NJ 08854 (US) The present invention discloses the cosmetic applications of (21) Appl. No.: 11/696,187 alkylalkanols collectively referred to as policosanol, for control of sebum secretion, as anti-acne component and as (22) Filed: Apr. 4, 2007 emollient. US 2007/0196507 A1 Aug. 23, 2007

COMPOSITIONS AND METHODS CONTAINING surface of the film is coated with a lipid porous adhesive HGH PURITY FATTY ALCOHOL C24 TO C36 layer that enables the tape to adhere to the skin surface. The FOR COSMETIC APPLICATIONS tape is applied to the skin test site for optimal period of 1 hr. Sebum is absorbed into the tape, displacing the air in the CROSS REFERENCE TO EXISTING microcavities. As this occurs, the lipid-filled cavities become APPLICATION transparent to light. Through this process, the sebum output 0001. This application is a divisional application of U.S. from each follicle forms a sharply defined clear spot, its size patent application Ser. No. 10/604.203 titled “Commercially roughly corresponding to the sebum Volume. viable process for high purity of fatty alcohol C24 to C36 0016. When the sebutape are placed on the black back and its cosmetic application for skin hair and nails' filed on ground of the score card, the sebum on the tape becomes Jul. 1, 2003. clearly visible as black spots. These spots are scored by a panel of cosmetologists on a scale of 0-5. These are pooled BACKGROUND OF THE INVENTION and from the mean of the scores, the percentage change is 0002 Policosanol is a natural mixture of higher aliphatic calculated from the control treatment site. primary alcohols (C24-C36) isolated from Sugarcane wax and beeswax. It contains 1-Octacosanol, Triacontanol, Tet 0017. The safety and adverse events like erythema, burn racosanol, Hexacosanol, Heptacosanol. These C to C. ing sensation, itching, urticaria, edema, dermatitis, ochro primary alcohols are also found in Sugarcane wax, ricebran nosis, dryness of skin and any other non specific reactions, wax, beeswax and various vegetable wax. if any, were monitored. 0018. The Policosanol colloidal solution was applied 0003. The structures of these primary alkanols are shown twice a day on one side of the forehead area for seven days. below. Pre-cleansing with soap/water was done before applications. The following observations were made

C2 Tetracosanol CH(CH2)2CH2OH 0.019, 2% and 5% Policosanol colloidal solution was C2. Hexacosanol CH(CH2)2CH2OH found to be safe for local application. It did not show any C28 Octacosanol CH(CH2)2CH2OH significant side effects and is safe for use on skin Co Triacontanol CH(CH2)2CH2OH C36 Tetratriacontanol CH3(CH2)2CH2OH 0020 Topical application of the Policosanol colloidal C27 Heptacosanol CH(CH2)2CH2OH Solution was found to decrease the sebum secretion in a concentration dependent manner. The 2% Policosanol solu tion reduced the sebum levels by about 11%, while 5% 0004 C. Tetracosanol CH (CH)2CH2OH solution reduced sebum secretion by 27%. 0005 C. Hexacosanol CH (CH2)CH-OH 0021. Both the self-assessment and the assessment by the panel of cosmetologist revealed that 100% of the subjects 0006 Cs Octacosanol CH (CH2)CH-OH showed marked decrease in sebum release. 0007 Co Triacontanol CH (CH)CHOH 0022. The colloidal solution was found to be effective in 0008 C. Tetratriacontanol CH (CH) CH-OH people with moderately high oily skin (scores >3.5). 0009 C, Heptacosanol CH (CH) CH-OH 0023. Additionally, one surprising observation was that 00.10 Evaluation of Policosanol on Sebum Levels in Policosanol treatment protected the 1.2 Hexanediol induced Human Volunteers dryness of skin and made the skin Smooth and soft.

0011 Study Methodology and Administration TABLE 1. 0012 Sixteen healthy males of between 18 and 25 years of age were included in the study after they had signed the Effect of Policosanol on the sebum secretion in human volunteers informed consent form. The main inclusion criterion was Sebum secretion Percentage those with oily skin (scores >4 on a 0-5 scale). All the (Mean Scores of reduction of Subjects were required to abstain from taking drugs, apply sebutape by a five sebum ing cosmetic products to their skin and exposing themselves Groups member panel) release to Sunlight or any other source of ultraviolet radiation Control 4.2 + 0.49 throughout the duration of the study. 296 3.71 - 0.41 11.6% Policosanol 0013 2% or 5% Policosanol colloidal solution in 1.2 (n = 8) 59 3.29 - O.33 27.66% hexanediol was applied (0.2 ml) for seven days, twice daily, Policosanol on the forehead. One side of forehead being treatment and (n = 8) the other side being the control (1.2 hexanediol treatment). 0014. The efficacy was evaluated based on self-assess ment and on the assessment of a panel of five independent 0024 Anti-microbial Study against Propionibacterium cosmetologists, visually, using Sebutape (CuIDerm Corp., CaS Dallas, Tex.). 0025 To carry out the antibacterial activity of the prod 0.015 The sebutape is made of microporous, hydrophobic ucts against Pr: acnes, the organism was first cultured in the polymeric film composed of many tiny air cavities. The anaerobic environment for which the anaerobic chamber US 2007/0196507 A1 Aug. 23, 2007

was used. To standardize the growth of anaerobic culture of Pr: acnes in the anaerobic chamber, different culture media -continued were used. 0026. The anaerobic chamber Model 8301-230, 3 ft Conc. polymer used in the study was purchased from COY of the Zone of inhibition LABORATORY, USA which is provided with an automatic sample (in mm) Air lock purge system. 0027. The anaerobic condition in the chamber was main SI. No. (%) Policosanol Clindamycin tained by initialization with N gas and then the mixture of gases of N+H+CO in the proportion 80+10+10. Two gas 4 O.S O.O O.O tank arrangement was made wherein only Na was connected to the transfer chamber and mixed gas to the main chamber 5 O.O1 O.O O.O using Gassing Manifold (Hrishi Biotech, Pune, India) 0028 Preparation of Anaerobic Media 0036) As seen in the results above, Policosanol is effec 0029. The anaerobic media were prepared by heating the tively inhibiting Propionibacterium acnes in concentrations media while passing the mixture of gases of N and CO in above 1% and the activity is comparable with Clindamycin 4:1 proportion simultaneously. The media were added with gel. Inhibition of anaerobic organisms coupled with a redox indicator resaZurin: 0.001% which is colorless in decrease in sebum Secretion complements to its use in the presence of anaerobiasis and shows blue color in its cosmetic formulations to control acne, as anti-seborrhea and absence. It was dispensed to 30/20/10 ml vials and sealed antimicrobial, additionally could provide moisturizing prop with rubbers and aluminum clamps and sterilized by auto claving at 121° C. for minutes erties. Policosanol could be used alone or in combination with other antibacterial, blemish erasers, sunscreen boosters 0030 Antimicrobial Study amongst others. 0031 Preparation of the inoculum The culture used in the 0037 Cosmetic Formulations based on Policosanol are study is Propionibacterium acnes ATCC 11827. The culture described in the following examples. from the broth was inoculated to the fresh medium in vials (10%) and incubated for 48 hours at 37° C. The optical density (OD) of the culture at 625 nm was measured. It was EXAMPLE 3 maintained between 0.64 and 0.80 which contains approxi mately 12x10 cells/ml 4.0 MC Farland standard Sebum Control Anti-acne Cream 0032) Procedure 0038 0033 Medium used for this study was reinforced clostridial agar (RCA). The medium that was prepared and sterilized in 30-ml vials was poured into the plates inside the Percentage chamber and allowed to solidify. Actives 0034. The culture was inoculated 0.3 ml/plate into the plates and spread. After 30 minutes, antibacterial sterile Boswellin CG O.2 discs 6 mm) were dispensed (2/plate). 2.5, 5.0. 7.5 and 10 Policosanol 1.O ul of the prepared samples and controls were dispensed onto Coleus oil 2.O Vit E 1.O the discs. The plates were incubated inside the anaerobic THP O.1 chamber at 37° C. for 48 hours duration. Passives

0035 Policosanol in different concentrations (0.1-2%) Cetyl Alcohol 4.0 prepared in 12 Hexanediol was used as vehicle for the study Glyceryl monostearate 3.0 with 1.2 Hexanediol as control. Clindac A (Clindamycin Cetostearyl alcohol 3.0 Phosphate Gel 1% w/w) was used as positive control. The Isopropyl myristate 2.O clearance Zone formed around the discs were measured and Myristyl myristate 1.O expressed in mm. The results of the study are given below Light liquid paraffin S.O Cetyl palmitate 1.O BHT 1.O BHA O.S Conc. CM-1OOO 2.O of the Zone of inhibition Glycerin 2.O sample in mm EDTA tetra sodium O.O2 DM Water 71.O SI. No. (%) Policosanol Clindamycin MPS O.2 1 2.0 12.O 11.O PPS O.O2 2 1.5 9.0 9.0 ImidUrea O.15 3 1.O 8.0 8.0 US 2007/0196507 A1 Aug. 23, 2007

EXAMPLE 4 -continued Sebum Control Sunscreen Cream Percentage 0039) DM Water QS MPS O.2 PPS O.O1 Imidurea O.15 Percentage Sodium Alginate O.13 Perfume O40 Actives

Tetrahydrocurcuminoids O.2 Vit E O.S EXAMPLE 6 Policosanol 1.5 Ethyl P-methoxy cinnamate S.O Avobenzone 2.0 Anti-dandruff, Anti-seborrhic, Hair Oil Passives 0041) Cetyl Alcohol 2.0 Glyceryl monostearate 3.0 Cetostearyl alcohol 1.O sopropyl myristate 2.0 Percentage Spermaceti wax 2.0 Myristyl myristate 2.0 Actives Stearic acid S.O PGDCC 1.5 Brahmi (oil extract) 6.63 Olive oil. Almond oil 1.O Neem oil limonoids O.15 Cetyl Palmitate 1.O Vit E O.2 BHT O.2 Policosanol O.S BHA O.O2 Rosmarinic acid (98%) O3S Glycerin 3.0 Passives EDTA tetra sodium O.O2 DM Water 67.0 Lauriforte 3.0 Xylosin O6 Medium chain triglycerides 1O.O MPS O.2 Isopropyl myristate 79.0 PPS O.O2 BHT O.OS midurea O.15 Perfume O.3

EXAMPLE 5 What is claimed is: Sebum Control Moisturizing Complex 1. A composition for topical treatment of acne comprising 0.05-10% w/w of policosanol formulated with suitable car 0040 riers. 2. A composition for topical application to control sebum secretion in the skin or the scalp comprising 0.05-10% Percentage policosanol formulated with suitable carriers. 3. A composition for use as topical emollient in the Actives treatment of dry skin conditions comprising 0.05-10% poli Xyloglucan O.15 cosanol formulated with suitable carriers. Umbelliferin 2.0 4. A composition as in claim 1 which additionally contains Vit E 1.O one of more natural extracts selected from the group con Policosanol 1.5 Almond Oil 1.O sisting of Boswellia serrata extract, Coleus forskohlii oil, Passives Vitex agnus-castus oil, Indian date extract, tetrahydrocur cuminoids, tocopherols, Kaempferia galanga extract, Ter Cetyl Alcohol 4.0 minalia belerica extract, garcinol. Spermaceti Wax 4.0 Squalene 3.0 5. A composition as in claim 2 which additionally contains Isopropyl myristate 3.0 one or more natural extracts selected from the group con Myristyl myristate 3.0 sisting of Bacopa monniera extract, Indian date extract, Stearyl Stearate 1.O Vitex agnus-castus oil, Terminalia belerica extract, garcinol, Cetyl palmitate 1.O BHT 1.O Azadirachta indica extract, rosmarinic acid. BHA O.O1 6. A composition as in claim 3 which additionally contains Glyceryl Mono Stearate 4.0 one or more natural extracts selected from the group con MCT Oil 2.0 Glycerin 3.0 sisting of coriander seed oil, avacado oil, sandal seed oil, Carbopol O.18 Xyloglucans, beta-glycans. EDTA tetra sodium O.O2