Patent Application
20240398694
This application claims priority to Thailand Application No. 2301003362, filed Jun. 2, 2023, which is incorporated herein by reference in its entirety.
The present invention relates to cosmetic science in respect of the skincare composition containing Shatavari extract.
Shatavari (or rak sam sib in Thai) is a scientific name for Asparagus racemosus Willd., which literally means the woman who possesses a hundred of husbands. This plant is the climber that wrapped around the other plants with spikes. Its roots are underground, similar to fingerroot. This plant is one of the succulents that are distributed in Thailand, India, Sri Lanka, Java, China, Malaysia, and Australia.
Rasayana, the science of youth and femininity in Ayurvedic scriptures, has been using Shatavari for over 3,000 years for youth, nourishing the womb and milk of mothers, and nourishing the body and skin of women. Pharmacological data showed that substances found in the roots are isoflavones and steroidal saponins, which have estrogen-like effects. Therefore, it plays a role in making the skin firm and moisturized, reducing wrinkles, slowing down aging, inhibiting 5α-reductase, controlling the face skin's oiliness, stimulating hair growth, and inhibiting tyrosinase for reducing blemishes, removing dark spots, and making the skin bright.
Natural vitamin C, in the form of L-ascorbic acid, has high antioxidant activity. In dermatology, it is used to prevent and treat skin aging caused by light. It is also used to treat dark skin conditions. It was found that applying 10% vitamin C could reduce the skin's redness from UVB exposure by 52% and sunburn by 40-60% and promote collagen production. The efficiency of vitamin C is 4 times higher when used in combination with vitamin E. It was found that the skincare formulation containing 15% vitamin C, 0.5% ferulic acid, and 1% vitamin E had 8 times higher efficiency. However, light affects the stability of natural vitamin C. Therefore, vitamin C, in the form of magnesium ascorbyl phosphate, is used. The effectiveness of antioxidant activity, skin protection from light, and stimulation of collagen production were reported in Telang P. S. 2013. Vitamin C in dermatology. Indian Dermatol Online J. 4(2): 143-6. However, Al-Niaimi F. and Chiang N. Y. Z. 2017. Topical vitamin C and the skin: Mechanisms of action and clinical applications. J Clin Aesthet Dermatol. 10(7): 14-7 disclosed that magnesium ascorbyl phosphate or the other forms of vitamin C did not increase L-ascorbic in the skin. In the double-blinded test of placebo and 10% vitamin C controlled groups of 10 volunteers, they further reported a statistically significant difference in reducing skin aging caused by light and reducing wrinkles. In another double-blinded test of placebo and 5% vitamin C controlled groups of 20 volunteers, they also found a statistically significant difference in reducing wrinkles.
At present, there are patents, petty patents, and patent applications in Thailand and internationally related to the skincare composition containing Shatavari extract, as follows:
International Patent Application No. WO2010086724A3, titled “Herbal cream and lotion compositions and methods of preparation thereof,” disclosed the herbal cream and lotion comprising the herbal extract prepared by employing a supercritical fluid extraction or water extraction, essential oils, pharmaceutically acceptable excipients, and methods of preparation thereof, in which the extract is selected from Shatavari, 0.0001-0.5%.
International Patent Application No. WO2010106417A3, titled “Herbal personal care formulations and method of preparing the same,” disclosed ingredients comprising herbal extract employing supercritical fluid extraction or water extraction, enzymes, essential oil, cosmeceutically acceptable excipients, and methods of preparing the same, of which various herbal extracts are of 0.5-2%, and the extract is selected from Shatavari.
Japanese Patent Application No. JPH1192332A, titled “Skin preparation composition for external use,” disclosed a cosmetic composition or cosmeceutical capable of sustaining a moisture-retaining effect and reducing dermatitis, in which comprises the extract of Asparagus africanasua and/or Kigelia africana, greater than or equal to 0.1% of dry weight.
Japanese Patent No. JP2010159213A, titled “Antioxidant,” disclosed an antioxidant, an anti-oxidizing external preparation for skins, and an anti-oxidizing cosmetic that contains the extract of one or more plants. The extract can be selected from Ficus benghalensis, Asparagus racemosus, Achyranthes aspera, Lawsonia alba, and Plumbago zeylanica.
European Patent Application No. EP2248526A1 (Withdrawn), titled “Compositions containing an extract of Asparagus and use thereof,” disclosed a cosmetic composition or cosmeceutical for treating acne and reducing the appearance of oil or pores on the skin that contains Shatavari extract.
U.S. Pat. No. 5,693,327A (Expired), titled “Herbal compositions,” disclosed a composition for the treatment. The composition comprises Melia azadirachta and/or Centratherum anthelminthicum, which further comprises Asparagus racemosus.
Due to the limitations of the unknown amount of the active Shatavari extract that binds to the epidermal estrogen receptor, inhibits tyrosinase, inhibits 5α-reductase, and is non-cytotoxic, which would not be apparent easily to the person skilled in the art in this field, the analyses as in drug research are required. In order to obtain the extract concentrations suitable for the formulations, various human cell types were cultured, such as human skin cells, prostate cancer cells, and breast cancer cells, and then cells, enzymes, and the expression of related genes were tested with the extract at various concentrations. The inventor has tested pharmacological effects and found that Shatavari extract has a very potent activity in stimulating estrogen hormone receptors at concentrations from 0.0001 (10,000-fold dilution) and up to a concentration of 0.001 (1,000-fold dilution), as well as inhibiting 5α-reductase. The non-cytotoxic concentrations start at 10,000 μg/mL, and the highest concentration is 10 μg/ml. It also inhibits tyrosinase, but inhibits collagenase activity only 0.03 times that of vitamin C. When considering the existing commercial products, there are products containing 15% vitamin C, 0.5% ferulic acid, and 1% vitamin E. As vitamin E is dissolved in oil, it is not suitable for water-based cosmetic formulations that focus on facial oil control. Thus, the inventors developed more efficient cosmetic formulations to change from ordinary cosmetics to cosmeceuticals, which have therapeutic effects. By adding Shatavari extract, the activity becomes more specific and is non-cytotoxic. In one embodiment, the formulation might further comprise L-ascorbic acid, a particular form of vitamin C, but in a smaller amount than is used in commercial products. The vitamin C in this invention is 1-4%, which is lower than the products on the market that have been used for a long time, causing it to be believed in the cosmetic industry that there must be 10-15% of vitamin C in the formulation in order to provide the best performance. Previous studies have tested the efficacy of vitamin C on the skin of volunteers; however, this invention tested the efficacy of vitamin C on cultured human skin cells under conditions in which environmental factors were controlled and the measurement accuracy was higher. In comparison, the amount of vitamin C in this invention is 2-7.5 times less than that of other products on the market. Besides reducing the cost of raw materials, this also solved the technical problem of the solubility of vitamin C in formulations containing Shatavari extract and/or niacinamide, which allows the product to contain more active ingredients than high-vitamin C products alone. Previously, this formulation could not be formulated successfully by using high amounts of vitamin C. In addition, high doses of vitamin C also cause irritation. This invention claims the formulation contains a small amount of Shatavari extract, only 0.01-2%. Unexpectedly, the amount of Shatavari extract, smaller than that of the previous invention, was shown to be effective in stimulating the growth of breast cancer cells, which is representative of estrogenic activity studies. It was also 767,358.626 times better than the standard β-estradiol. These results were calculated from Shatavari extract at a concentration of 0.001 (diluted 1,000 times), causing breast cancer cell survival to be the highest by 139.70%, compared to the standard substance at a concentration of 1,000 times, which could make breast cancer cell survival the highest at only 107.2%. Therefore, the determination of Shatavari extract content in this invention can produce an effective formulation, according to research. Shatavari extract's binding to estrogen receptors in such particular amounts results in stimulating the growth of epidermal cells. This makes skin cells firm and plump again. In addition, it has an inhibitory effect on 5α-reductase, which directly affects hair loss and the amount of oil produced by the sebaceous glands around the hair follicle. It also inhibits tyrosinase, thereby affecting the proliferation and inhibition of melanin production, resulting in bright skin, and reducing blemishes and dark spots.
The skincare composition of this invention contains particular amounts of Shatavari extract. These particular amounts were tested on human skin cells, prostate cancer cells, and breast cancer cells for enzymes and gene expression and showed that they are effective in stimulating estrogen receptor, and inhibiting 5α-reductase and tyrosinase. This converts the dose applied to the cells to be suitable for skin application pharmaceutically. The composition contains only a few essential substances; therefore, it does not interfere with the absorption of active ingredients and cause no irritation. In one embodiment, a skincare gel comprises edetate disodium, high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, low molecular weight hyaluronic acid, niacinamide, Shatavari extract, 2-phenoxyethanol, carbomer, lactic acid, and water. The uses of Shatavari extract in said particular amounts also include using fewer ingredients, resulting in decreased production costs and easier production.
The skincare composition containing Shatavari extract for preparation of the product used with the body, scalp, or skin; particularly, skincare products for binding to the epidermal estrogen receptor, inhibiting tyrosinase, and/or inhibiting 5α-reductase, in a form selected from the group consisting of gels, essences, lotions, sprays, essences for masks, or scalp tonics. Said skincare composition comprises:
This invention further comprises:
This invention also discloses suitable amounts of the ingredient, which is 0.6-2 grams of Shatavari extract, wherein Shatavari extracted by co-solvent between ethanol and supercritical carbon dioxide is preferred. Moreover, 95-97% ethanol is used, and/or Shatavari is extracted by 70% ethanol mixed with the surfactant according to the method of Thai Petty Patent No. 20550.
This invention will be described in detail hereafter.
The chelating agent is selected from any one of edetate disodium, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid metal salts, or a combination thereof.
The moisturizer is selected from any one of hyaluronic acid, high molecular weight hyaluronic acid (higher than 1,800,000 Da), medium molecular weight hyaluronic acid (1,000,000-1,800,000 Da), low molecular weight hyaluronic acid (400,000-1,000,000 Da), hyaluronic acid S (100,000-400,000 Da), aloe vera gel (powder), nutto gum, hydrolyzed protein, urea, amino acid, cholesterol, sodium L-pyroglutamate, sodium lactate, propane-1,2,3-triol, or a combination thereof.
The preservative is selected from any one of benzyl alcohol; benzoic acid, or salts, or esters thereof; propionic acid, or salts thereof; salicylic acid, or salts thereof; sorbic acid, or salts thereof; o-phenylphenol, or salts thereof; 4-hydroxybenzoic acid, or methyl-, ethyl-, esters, and salts thereof; undec-10-enoic acid, or salts thereof; benzyl alcohol; 2-phenoxyethanol; 3-(2-ethylhexyloxy)propane-1,2-diol; methyl paraben; propyl paraben; methyl parahydroxybenzoate; propyl parahydroxybenzoate; 2-bromo-2-nitropropane-1,3-diol; imidazolidinyl urea; methylisothiazolinone; ethylenediaminetetraacetic acid; methyl paraben; propyl paraben; or a combination thereof. Salts mean sodium, potassium, calcium, magnesium, ammonium, and ethanolamine salts/chloride, bromide, sulphate, and acetate salts.
Esters mean the ester of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and phenyl.
This invention may further comprise the following:
Gelling agent selected from any one of carbomer, xanthan gum, arabic gum, carrageenan, cellulose, synthetic cellulose, mucilage in okra, or a combination thereof.
This invention also provides examples that can be easily understood by a person of ordinary skill in the art, but it is not limited by said examples.
A soothing skincare gel comprises:
This invention further comprises the production method of the soothing skincare gel composition according to Example 1. The method comprises the following steps: adding edetate disodium into water; stirring until dissolved; adding high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, low molecular weight hyaluronic acid, niacinamide, Shatavari extract, and 2-phenoxyethanol into the solution; stirring until dissolved; keeping the reaction until used; adding carbomer into the solution; mixing thoroughly; adjusting pH with a lactic acid solution to 5.5.
This invention may further comprise panthenol, L-ascorbic acid (1-4 grams), ferulic acid.
A skin brightening and nourishing essence comprises:
A skin-moisturizing spray comprises:
An essence for masks comprises:
A scalp tonic product for reducing hair loss comprises:
This invention will be described in detail hereafter. The production method of products containing the composition according to Examples 2-5 is similar to the disclosed production method of the soothing skincare gel composition according to Example 1. Different preservatives may be used, and the pH value may be different; however, the production method is the same. The different ingredients, such as panthenol, L-ascorbic acid, ferulic acid, and propane-1,2,3-triol, are mixed in the same step as niacinamide.
This invention may further comprise the following:
A cosmetic wax is selected from any one of shea butter, mango wax, avocado wax, cupuacu butter, coconut wax, cacao wax, petrolatum, beeswax, stearyl alcohol, cetyl alcohol, or a combination thereof.
A substitute for beeswax, an emulsifying wax, is ceteareth-20, candelilla wax, cetearyl alcohol, carnauba wax, or soy wax.
A cosmetic oil is selected from any one of flaxseed oil, jojoba oil, rosehip oil, avocado oil, perilla oil, Sacha Inchi oil, coconut oil, caprylic or capric triglyceride, sunflower seed oil, castor oil, olive oil, carrot seed oil, argan oil, tea seed oil, or a combination thereof.
A ceramide is selected from any one of ceramide 1, ceramide 1A, ceramide 2, ceramide 3, ceramide 6, ceramide 6 II, ceramide AP, ceramide AS, ceramide EOP, ceramide EOS, ceramide NP, ceramide NS, or a combination thereof.
An emulsifier is selected from any one of propane-1,2,3-triol, hydrogenated lecithin, polyoxyethylene 20 sorbitan monooleate, polyoxyethylene 23 dodecanol, triethanolamine, or a combination thereof.
This invention also provides examples that can be very easily understood by a person of ordinary skill in the art, but it is not limited by said examples.
A concentrated, nourishing skin lotion for combating skin allergies and dry itching comprises:
This invention further discloses the production method of concentrated nourishing skin lotion for combating skin allergies and dry itching, containing the composition according to Example 6. The method comprises the following steps: adding edetate disodium into water; stirring until dissolved; adding high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, low molecular weight hyaluronic acid, niacinamide, Shatavari extract, and benzyl alcohol; stirring until dissolved; keeping the reaction until used; heating the solid ingredient, which is shea butter, at a temperature of 70-90° C. until melted; adding the oil ingredients, including hydrogenated lecithin, flaxseed oil, and jojoba oil; when it cooled down, yet in a liquid state, adding ceramide 1, ceramide 2, ceramide 3, and α-tocopherol into the reaction; mixing thoroughly; adding the water phase kept previously; adjusting pH; storing at a temperature of 8-20° C. until solidification and stirring with a blender until a fluffy texture is formed.
A soothing, moisturizing, anti-oxidant, skin-nourishing lotion comprises:
Glycerin (or glycerine), or glycerol, is a name according to the International Nomenclature for Cosmetic Ingredients, or INCI. Propane-1,2,3-triol is a name according to the International Union of Pure and Applied Chemistry, or IUPAC.
Caprylic or capric triglyceride is the universal name of a cosmetic ingredient. It is made of coconut oil processed by lipid and water separation (fractionated coconut oil). Its trademark name is Myristol 318.
A pH-adjusting agent includes triethanolamine, lactic acid, glycolic acid, and citric acid. Lactic acid is preferred.
The use of the composition according to this invention is for product preparation so that the product can be used on the body or skin, particularly skincare products that bind to the epidermal estrogen receptor. The form product can be selected from the group consisting of gels, essences, lotions, sprays, essences for masks, or scalp tonics. The inventor has submitted Shatavari extract under the trademark name Rejeunir®. Its production method was patented under Thai Petty Patent No. 21300. The pharmacological effects were tested as follows.
Breast cancer cells are the representatives of the study of estrogen receptor stimulation activity because breast cancer cells are responsible for estrogen hormone. According to the estrogen hormone stimulation activity study, Shatavari extract concentration of 0.001 micrograms per milliliter (diluted 1,000 times) has the highest % survival of breast cancer cells MCF7, at 139.70+10.34%. This is 1.3032 times higher than that of the standard β-estradiol, which the highest % survival of breast cancer cells MCF7 is 107.20+5.37% at a concentration of 1,000 micrograms per milliliter.
The % survival of breast cancer cells MCF7 when treated with Shatavari extract at various concentrations is shown in Table 1 and
Prostate cancer cells are the representatives of the study of 5α-reductase inhibition activity due to the production of 5α-reductase in prostate cancer cells. According to the study of 5α-reductase inhibition activity, Shatavari extract is non-cytotoxic to prostate cancer cells DU-145 at the highest concentration of 10,000 micrograms per milliliter, which is 87.17+1.92% cell survival. Standard finasteride is non-cytotoxic to prostate cancer cells at the highest concentration of 10 micrograms per milliliter, which is 96.78+1.20% cell survival.
The % survival of prostate cancer cells DU-145 when treated with Shatavari extract at various concentrations is shown in Table 3 and
The % 5α-reductase inhibition of Shatavari extract and the standard finasteride are shown in
From the collagenase inhibition activity study, Shatavari extract is able to inhibit collagenase (IC50 0.33+0.05 milligrams per milliliter), as shown in
The vitamin C concentrations used in the collagenase inhibition activity study are 1, 0.1, 0.01, 0.001, and 0.0001 milligrams per milliliter. These are used in the collagenase inhibition activity study that use P-z peptide as a substrate. In a triplicate test, the IC50 inhibiting collagenase is 0.01+0.003 milligrams per milliliter. Thus, the suitable vitamin C concentration in collagenase inhibition starts at 0.01 milligrams per milliliter, or 1% in the product. The most suitable vitamin C concentration in collagenase inhibition is 0.02 milligrams per milliliter, or 2% in the product. These are different from the amounts of vitamin C in common commercial cosmetic products, which use between 10 and 15% of vitamin C. The excessive use of vitamin C, far from the research data, not only wastes it but also makes it harder to formulate due to its solubility, acidity, and incompatibility with other ingredients. The inventors, thus, use vitamin C in the cosmetic product in particular amounts of 1-4% to achieve collagenase inhibition.
From the free-radical DPPH binding study, Shatavari extract has an SC50 of 5.92+0.03 milligrams per milliliter. This is 0.0034 times that of vitamin C, of which SC50 is 0.02+0.01 milligrams per milliliter. Also, the free-radical DPPH binding activity of non-diluted Shatavari extract is 91.15+0.97%.
The vitamin C concentrations used in the free-radical binding study are 100, 10, 1, 0.1, and 0.01 milligrams per milliliter. These are used in free-radical binding studies by the DPPH method and in free-radical nitric oxide binding using Griess reagent. In a triplicate test, the IC50 values of free-radical binding by the DPPH method and free-radical nitric oxide binding are 0.02+0.01 and 0.84+0.02 milligrams per milliliter, respectively. Therefore, the suitable vitamin C concentration for free-radical binding starts at 0.02 milligrams per milliliter, or 2% in the product. The most suitable vitamin C concentration for free-radical binding is 0.04 milligrams per milliliter, or 4% in the product. These are different from the amounts of vitamin C in common commercial cosmetic products, which use between 10 and 15% of vitamin C. The excessive use of vitamin C, far from the research data, not only wastes it but also makes it harder to formulate due to its solubility, acidity, and incompatibility with other ingredients. The inventors, thus, use vitamin C in the cosmetic product in particular amounts of 1-4% for free-radical binding activity by the DPPH method, and for free-radical nitric oxide binding which causes anti-inflammation activity.
According to the study of tyrosinase inhibition activity, Shatavari extract has an IC50 of 671.82+13.45 milligrams per milliliter. This is 0.00003 times that of kojic acid, of which IC50 is 0.02+0.00 milligrams per milliliter. Also, the tyrosinase activity of non-diluted Shatavari extract is 113.60+0.09%.
In conclusion, Shatavari extract is very high effective in stimulating estrogen and high effective in inhibiting 5α-reductase. It is able to bind free-radical DPPH and moderately inhibit tyrosinase. Although it has low collagenase inhibition activity, this could be compensated for by adding vitamin C to the formulation. The final products cannot be tested for their pharmacological activities by the same method as the extract because the ingredients in the formulation interfere with optical absorption. Also, it is hard to interpret results as it becomes opaque when dissolved in cell culture media. Similarly, Shatavari extract in the anti-inflammation activity study with the nitric oxide method also becomes opaque, resulting in difficulty in interpretation.
The best mode of invention is mentioned above in the detailed description section.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2301003362 | Jun 2023 | TH | national |
