FIELD OF THE INVENTION
The present invention relates to facilitate an effective base composition for delivery of active ingredients into the skin in desired ratio. More particularly the invention relates to an effective and enhanced transport of active ingredients at the required ratio in to the skin using the base composition.
BACKGROUND AND THE PRIOR ART
In the present age people are very concerned with maintaining and protecting the glow of their skin from the pollution of environment. The ultraviolet ray of sun, air pollution, exert severe stress on the skin and accelerate the natural aging process, resulting in wrinkles, loss of firmness and elasticity, age spots, discoloration, dryness, and other cosmetically undesirable effects. For reducing wrinkles, acne and other problems of skin people go for cosmetic surgery such as liposuction; these also can cause additional damage to skin.
Presently there are a number of cosmetic products available in the market which give solutions to skin problems.
U.S. 5968533 discloses a skin care compositions and methods are provided for improving the appearance of skin affected by aging, photodamaee and/or oxidative stress. Adhesive materials containing cosmetically active ingredients, e.g., one or more antioxidants such as Vitamins A. C and/or E, or moisturizess are applied in concentrated dry powdered form to target areas including the frownline area of the forehead, the front of the neck. the crows-feet area near the eyes. the upper lip and the nasolabial area using a transdermal patch having an acidity approximating human skin acidity of 5.5. preferably by an appropriate ratio of ascorbic acid and ascorbate salts. US 5968533 provide the delivery system of effective concentration of the active ingredients to the skin tissue matrix (the dermal layer) where at least some of the main ingredients are lost during the delivery to skin. Moreover it uses direct actives to be deposited on the skin.
Antioxidant is a very essential component to keep skin young and beautiful. The anti aging creams are rich with different kinds of antioxidant components. The very common and effective antioxidant component used in the cream is β-Carotene and Lycopene.
The benefit of a cosmetic product containing a functional ingredient is realized when the product is delivered into the skin and particularly at the desired composition. The present

invention overcomes the problem of the loss of the active ingredients during delivery to the skin by delivering the antioxidants at the desired ratio.
OBJECTIVE OF THE INVENTION
Therefore it is an object of the present invention to deliver a mixture of carotenoids at the desired ratios into the skin.
A further objective of the present invention is to provide enhanced transdermal delivery of ingredients.
Another objective of the present invention is to provide a base with unique combination ingredients capable of delivering the actives in a required ratio without any loss of the active ingredients over that present in the composition.
Yet another object of the present invention is to provide protection of skin from various damages.
BRIEF DESCRIPTION OF ACCOMPANIED DRAWING
Figure 1: Shows a Static Franz Cell
DETAILED DESCRIPTION OF THE INVENTION
According to the preferred embodiment of the present invention there is provided an advanced base composition for transporting a mixture of active ingredients onto the skin cells at the desired ratio so that the amount present in the composition is delivered on to the skin without loss in delivery. The said base is useful for delivery of any actives without loss of the same from the composition to the site of action. The said actives could be skin benefit agents, cosmetic agents, pharmaceuticals for topical applications and the like. The base could be in form of cream, lotion, gel, paste, stic, etc. It is well known that the mixture β-Carotene and Lycopene produce a synergistic antioxidant (radical quenching) effect and particularly, this mixture produce an enhanced synergistic activity at a ratio of 80% (β-Carotene) and 20% (Lycopene.. Therefore, it is important that the skincare formulations made with this mixture of β-Carotene and Lycopene maintains the ratio of 80 and 20. However, maintaining the desired carotenoids ratio in the cream alone will not benefit the end-user but a transdermal delivery of these carotenoids at a desired ratio on to the end-user is required to achieve optimal effects of the active.

The transdermll delivery of an ingredient is influenced by several factors including the type of base/vehicle used. The base composition of the present invention is capable of transporting the actives to the skin without substantial loss in the same. The compositions of actives present in the formulation are almost equivalent to the active depostted on the skin. The present inventors have found that the base is preferably a cream base comprising the components Aqua, Disodium EDTA, Glycerin, Propylene Glyco,, Steareth-2,, Steareth-2, Isopropyl Palmitate. Petrolatum, paraffin wax. Cetyl Alcoho,, Ethylhexyl Methoxycinnamate, Mineral oil. Methylparaben, Propylparaben, Hydrogenated Avocado Oil. Hydroxyethyl Urea. Polysorbate 85 (and) Mineral oil (and) Acrylates/Acrylamide copolyme., Cyclopentasiloxane, dimethiconol, dimethicone crosspolymrr and phenyitrimethicone blend, Pantheno., Phenoxyethanol, Fragrance as disclosed in Table I.



The cream base of the present invention is capable to deliver the active ingredients to the skin in the amount as present in the composition with the cream base. As mentioned above the actives could be any cosmetic, dermatological, pharmaceutical active. The inventors of the present invention have described the present invention with non-limiting active of carotenoids. The two carotenoids namely β-carotene and lycopene are known to be active

when given in the ratio of 80:20. However it is found that in most composition in use the said ratio is not maintained. The present invention is described taking β-carotene and lycopene as exemplary illustration for deposition in required ratio of 80:20.
Another embodiment of the present invention involves two types of vehicles (cream-base) viz. Cream base of present invention and Standard Cream are used and their effect on the transdermal delivery of the mixture of carotenoids β-Carotene and Lycopene are studied. Standard cream is prepared using Aqua, Disodium EDTA, Steareth-2,. Steareth-2, Cetyl Alcohol. Mineral oil, Methylparaben, Propylparaben, Polysorbate 85 (and) Mineral oil (and) Acrylates/Acrylamide copolyme,, Phenoxyethanol. Fragrance. Porcine skin model is used because of its similarity to human skin, in terms of its morphology and the essential permeation characteristics.
The results obtained from this study indicated that the Cream base of present invention transported more carotenoids mixture than the Standard Cream. More importantly, the Cream base of present invention aided the transport of the carotenoids at the desired ratio into the skin.
The following example further describes and demonstrates the embodiments within the scope of the present invention. The example is given solely for the purpose of illustration and is not to be construed as limitation of the present invention as many variations thereof arc possible without departing from the spirit and scope. All percentages used herein are by weight of the composition unless otherwise indicated.
Example 1
Materials:
β-Carotene and Lycopene are obtained from DSM Nutritional Products, Mumbai, India. Pig skin (1) is obtained from local butcher. All other chemicals are used of analytical grade.
Preparation of cream formulation:
0.462 g of mixture of β-Carotene and Lycopene (80:20 %; 70:30 %; 50:50 %) taken and homogenously mixed with 49.538 g of cream base of present invention or Standard cream.
Preparation of Pig skin:

The porcine back skin (I) is provided by the local butcher. Back skin (I) of the pig is removed with an even level of subcutaneoss fat. 5 mm thickness strips of the skin are prepared by removing the subcutaneoss fat.
Method:
Transdermal experiment is conducted using Franz Diffusion Cell (Figure 1). The pig skin (1) (defatted, 5mm thickness) is placed between the donor (2) and the receptor (10) compartments. The receptor (10) is filled with 34 mL of 50% glycerol. To maintain a temperature of 37°C (heating/thermostat) water is circulated in the outer jacket (8) maintained at 37°e (Colipa Guidelines). The receptor (10) fluid is continuously stirred using magnetic beads, 1g of cream (base of present invention/Standard) containing mixture of commercial (OSM) fat-soluble sample of β-Carotene and Lycopene (in the ratio of 80:20 %; 70:30 %; 50:50 %) at 1% is added to the donor (2) compartment. Another diffusion cell is set up in a similar way with I% caffeine in the donor chamber and the diffusion of caffeine through the skin is used as a measure to test the integrity of skin. The experiment runs for a period of 24 hrs. The sample is collected, filtered through a 0.2 micron filter and analyzed using high performance liquid chromatography (HPLC). After 24 hrs, the remaining solution from the donor chamber is collected. Then the skin is removed, sonicated in 5 ml of acetone for 30 mins. Blank pig skin (1) is also sonicated with 5 ml of acetone. The resulting solution is collected, filtered and analyzed using HPLC. The other components of the Static Franz Cell are donor chamber (3), flat ground joint (4), heater/circulator (9), receptor chamber (6), stirbar (7). All samples are analysed in duplicates.
High performance liquid chromatography (HPLC) analysis is carried out for the above said samples using the following conditions:
Column: C18. 50 x 4.6mm, 1.8µ
Mobile Phase: Acetonitrile: Methanol: Dichloromethane (75:20:5).
Wavelength: 450nm and 472nm.

Calculations:
Amount of carotenoids in the skin: Area of Sample X Concentration of Standard
Area of Standard Concentration of Sample
Results of the Experiment
Cream base of present invention formulation is prepared with carotenoids mixture. This carotenoids mixture contained 80% β-Carotene and 20% Lycopene. The cream formulation is subjected to the transdermll study and the resulting samples are analysed as described above. Table 2 show the experimental details and the results.

The results showed that the Cream base of present invention transported the mixture of β-carotene and lycopene at the desired 80 and 20 in ratio. The mass balance of the carotenoids is calculated by measuring the carotenoids recovered from the donor. There is a significant loss with regard to both the carotenoids due to photo-oxidation (Table 2). However, the loss of carotenoids due to photo-oxidation is beneficial as the oxidation of carotenoids protects the skin lipids against oxidation.

For confirming the results of experiment 1, further experimenss are conducted using formulation with varying β-Carotene and Lycopene ratios. Table 3 shows the experimental details and the results.

It is observed in table 3 that during Treatment 1, Treatment 2, and Treatment 3 the input ratio and the output ratio. which is also the delivery ratio of β-Carotene and Lycopene to the skin, is almost same.
The above results confirm that the Cream base of present invention transported the carotenoids into the skin in the same ratio. as they are present in the cream.

To validate the observed effect of transporting carotenoids at the desired ratio by the Cream base of present invention, another cream base (Standard Cream) is prepared and similar experimenss are conducted as provided in Table 4.

The ratio of p-carotene and Lycopene in skin extract obtained after application of the Cream base of present invention treatment is found to be 80 and 20 but the ratio obtained for Standard cream treatment is found to be 70 and 30. The above results (Table 4) confirm that the Cream base of present invention aided the transport of carotenoids at the desired ratios in to the skin, but the Standard cream transported a random ratio (P < 0.05). In addition the Cream base of present invention transported more carotenoids than the Standard cream (P < 0.05).

We claim:
1. A transdermal base composition delivering any active ingredients in desired ratio without loss of active ingredients during delivery.
2. The base composition as claimed in claim 1 comprises ingredients selected from water, Sodium salt of poly amino carboxylic acid, Polyol / Triol, high degree ethoxylated ether of long chain alcohol, low degree Ethoxylated ether of long chain alcohol, fatty ester, vicinal diol, Fatty alcohol, wax derived from petroleum, hydrocarbon wax, fatty ester, liquid hydrocarbon, hydroxy benzoate ester, vegetable oil, salts or esters of acrylic acid alkenamide /amides, Silicon oil (low molecular weight), Glycol ether. Provitamin B5, Hydroxy carbamide, Aroma compounds.
3. The base composition as claimed in claim 1 comprises water in a range of 55.00 -75.00 percent by weight, Sodium salt of poly amino carboxylic acid in a range of 00.01 - 00.10 percent by weight, Polyol / Triol in a range of 00.50 - 07.50 percent by weight, high degree ethoxylated ether of long chain alcohol in a range of 01.00 -04.00 percent by weight, low degree Ethoxylated ether of long chain alcohol in a range of 00.50 - 02.00 percent by weight fatty ester in a range of 00.50 - 05.00 percent by weight, vicinal diol in a range of 00.10 - 02.00 percent by weight, Fatty alcohol in a range of 00.10 - 02.00 percent by weight, wax derived from petroleum in a range of 00.10 - 02.00 percent by weight, hydrocarbon wax in a range of 00.25 -02.50 percent by weight, fatty ester in a range of 01.00 - 08.50 percent by weight, liquid hydrocarbon in a range of 08.00 - 22.00 percent by weight, hydroxy benzoate ester in a range of 00.01 - 00.50 percent by weight, vegetable oil in a range of 00.10-02.50 percent by weight, salts or esters of acrylic acid alkenamide /amides in a range of 00.50 - 03.00 percent by weight, Silicon oil (low molecular weight) in a range of 00.50 - 05.00 percent by weight. Glycol ether in a range of 00.10 - 00.75 percent by-weight, Provitamin B5 in a range of 00.10 - 01.50 percent by weight, Hydroxy carbamide in a range of 00.10 - 02.50 percent by weight, Aroma compounds in a range of 00.10- 01.50 percent by weight.
4. The base composition as claimed in claim 1, wherein said actives are selected from skin benefit agents, cosmetic agents and pharmaceuticals for topical applications.

5. The base composition as claimed in claim 1, wherein the cosmetic agent active is beta carotene and lycopene.
6. The base composition as claimed in claim 3 wherein beta carotene and lycopene are present in weight ratio of 80:20.
7. The base composition as claimed in claim 1, which is in the form selected from cream, lotion, gel, paste, stic, etc.
8. The base composition as claimed in claim 1, which is cream.