WO2022150023A1

WO2022150023A1 - Wound healing and burn cream with camellia sinensis (white tea) essential

Info

Publication number: WO2022150023A1
Application number: PCT/TR2021/050457
Authority: WO
Inventors: Tolga MERCANTEPE; Ali Bilgin; Adnan YILMAZ; Levent TUMKAYA; Atilla TOPCU
Original assignee: Recep Tayyip Erdogan Universitesi
Priority date: 2021-01-05
Filing date: 2021-05-11
Publication date: 2022-07-14
Also published as: TR202100058A1

Abstract

The present invention relates to a wound healing and burn cream containing Camellia sinensis (white tea) extract that helps healing of skin lesions, particularly burn lesions and wounds. Said cream increases the synthesis of collagen fibrils by supporting the epithelial cells in the skin, ensures healing of skin lesions after burns or physical damage by reducing apoptosis and suppressing the production of free oxygen radicals. In addition, the inventive cream prevents skin wrinkles by increasing the number of collagen fibrils.

Description

WOUND HEALING AND BURN CREAM WITH CAMELLIA SINENSIS (WHITE TEA)

ESSENTIAL

Field of the Invention

State of the Art

Burn is a type of injury that results in losing the integrity of the skin due to high heat, extreme cold, electricity, friction, radiation or chemicals. Burns may occur due to many environmental factors. It may occur due to too much exposure to the sun, electric shocks, boiling water, fire or many other similar external factors. Today, most of the burns are caused by home accidents or the sun. Burns may occur in various forms such as; thermal burns (flame, steam burns), chemical burns (by contact with acid or base products), radiation burns (sun rays, tanning beds, etc.), electrical burns. Burn symptoms vary based on the severity of the burn. There may be peeling, skin discoloration and pain. The most common complication pertaining to burns is infection. Electricity burns cause compartment syndrome (edema in the area where the muscles gathered) and rhabdomyolysis (sudden and rapid damage to the muscle tissues in the body for any reason) due to damage to the muscles. It may cause a decrease in bone density and loss of muscle mass based on the degree of burn. The patient may experience stress disorder after trauma by being psychologically affected in major burns. There may be disturbing scars based on the degree and size of the burn. Sunburns may lead to skin cancer. Burns are evaluated in different severities as first, second and third degrees. Treatment is determined based on the degree of burn. The first and second degree burns heal within 2-3 weeks without leaving a scar with drug treatment. If more than 2/3 of the dermis are affected, scars and loss of function are seen. For this reason, it may require surgical intervention. Scar is formed and loss of function is seen and surgical intervention is required because the dermis and epidermis are completely burned in third degree burns. l According to the data of the World Health Organization (WHO) in the year 2014, more than 10 million people all over the world apply to hospitals for treatment purposes and about 3% of them result in death due to burns (Nzioka et at. 2016). Although burn treatments vary according to the degree and types of burns, more than half of the patients who apply to clinics due to burns receive ambulatory care as dressing treatment, particularly topical creams (Mantle et al. 2001 , Arslan et al. 2012). The market share of skin protective and therapeutic creams in the world is 6.7 billion dollars annually, and this number has been increasing for the last decade (Nzioka et al. 2016). Anti-inflammatory zinc oxide, antibiotic; topical creams containing heavy metals such as bacitracin, silver sulfadiazine etc., various topical creams ensuring wound closure, corticosteroids, creams containing imiquimod and interferons are used within this scope (Arslan et al. 2012, Shpichka et al. 2019). In the state of the art, in the studies performed, Silicone layers, wound care silicone gel layers (Mantle et al. 2001 , Arslan et al. 2012, Shpichka et al. 2019), silastic gel layers (Arslan et al. 2012, Builders et al. 2013, Nzioka et al. 2016, Shpichka et al. 2019), different types of silicone have been used, such as Sil-K silicone (Lee et al. 1996, Van Der Wal et al. 2010). Moreover, epiderm silicone layers or silicone gel treatments have only been studied in various patient populations such as Europe, Afro-American, Chinese, Indians, Malays and Eurasia; however, the treatment mechanisms were not reported in detail (Salman and Ozdemir 2018). Treatment methods of silicone gel layers are generally applied for 12-24 hours a day, except bath time (Akyuz 2008, Baktir 2020). Topical silicone gel is applied twice a day. The compatibility of these treatments with other treatments (if any) and not recording daily hygiene is considered. Today, these existing treatment methods cover a period ranging from 12 to 28 weeks (Sari et al. n.d., etinkaya O. 2001, Akyuz 2008, KURT OZKAYA et al. 2014). In addition to this, today, there are studies that can be obtained completely from herbal extracts (Allium cepa, Aloe vera, Santalum album, Acer palmatum) (Zhu and Gao 2008, Lorenti 2012). It was stated that the treatment expected from these creams with organic plant extracts in skin burns and skin lesions increases the number of collagen and reticular fibrils under the skin and assists in increasing mitotic activity by protecting the stratum germinativum layer (productive layer) in the skin epithelium (Sari et al. n.d., Carney et al. 1994, etinkaya O. 2001, Akyuz 2008, Stallings and Lupo 2009, Lorenti 2012, Builders etal. 2013, KURT OZKAYA et al. 2014, Shpichka etal. 2019).

The skin is the largest organ of the human body responsible for the protection, temperature regulation and sensitivity of the organism and consists of three layers: epidermis, dermis and hypodermis. The epidermis is the outermost layer of the skin and consists mostly of cells that are called keratinocytes. The dermis is the second layer of skin under the epidermal layer. The main cells in the dermis are fibroblasts and constitute the extracellular support matrix tissue of the dermis. Hypodermis is the lowest layer of the skin and consists of cells that are called lipocytes. In burn studies, although agents that have a direct effect on the epidermis are not known, there are many studies dealing with their effects on the dermis layer (Stallings and Lupo 2009, Builders et at. 2013, Anthonissen et al. 2016). Skin healing is a systemic process that comprises; hemostasis (coagulation), inflammation (mononuclear cell infiltration), proliferation (epithelization, fibroplasia, angiogenesis and granulation tissue formation) and maturation (collagen accumulation or tissue formation), respectively, in the wound area (Hermans 2005, Zhu and Gao 2008, Stallings and Lupo 2009, Lorenti 2012, Atat et al. 2015, Anthonissen et al. 2016, Shpichka et al. 2019). Each of these four systemic processes observed during the regeneration of the skin in skin burns vary based on various factors such as cause of the burn, its degree, size and general condition of the patient. The differences in the processes cause changes in the treatment of burns. The healing process may cause different results depending on the severity of the burn. Superficial burns heal within two weeks and cause minimal scarring. Re-epithelization of burns with partial thickness is provided by keratinocyte migration from the dermal extensions of the skin a few hours after the injury. In deeper burns; healing starts around the edges, but not in the center depending on the requirement of rapid wound closure (Sari et al. n.d., Stallings and Lupo 2009, Builders et al. 2013, KURT OZKAYA et al. 2014, Atat et al. 2015, Anthonissen et al. 2016, Shpichka et al. 2019, Baktir 2020). The acceleration of early cell proliferation that ensures quick recovery of burns is caused by dendritic cells that release various factors. Therefore, agents that increase dendritic cells are considered as therapeutics that improve burn-wound care (Vinish et al. 2016, Bae etal. 2017).

Today, studies are carried out so as to develop creams that are completely derived from plants organically to substitute the creams containing heavy metals such as topical zinc oxide and silver sulfadiazine used currently (Sari et al. n.d., etinkaya O. 2001, Hermans 2005, Akyuz 2008, Wolfram et al. 2009, Van Der Wal et al. 2010, Wasiak and Cleland 2015, Baktir 2020). The expected treatment of creams in skin lesions such as skin burns that are caused by contact with physical and chemical substances is to increase the number of collagen and reticular fibrils under the skin and to assist in skin healing with its positive effects on keratonocytes and dendritic cells in the skin epithelium (Hermans 2005, Li-Tsang et al. 2006, Sakallioglu et al. 2006, Wolfram et al. 2009, Zhang et al. 2010, Lorenti 2012, Degeorge et al. 2014, Wasiak and Cleland 2015, Vinish et al. 2016, Bae et al. 2017). It was reported that herbal flavonoids and catechins (EG), especially epigalactocatechin gallate (EGCG), have an important effect on increasing the number of collagen and reticular fibrils in the connective tissue under the skin in the studies performed within this scope (Huang et al. 2005, Lee et al. 2005, Jeong et al. 2007, Yoneyama et al. 2008, Domingo et al. 2010, Peairs et al. 2010, Kim et al. 2013, Li et al. 2016). Although it was reported in previous studies that the epigalactocateechin is mostly found in green tea, it was reported that epigalactocatechins are found mostly in white tea in recent studies. In addition to this, white tea has a very rich content (Islam 2011 , Oyetakinwhite et al. 2012, Salman and Ozdemir 2018, Yildirim et al. 2020).

Angiogenesis is induced by hypoxia-induced factor 1 and angiogenic cytokines such as VEGF and CXCL12 during healing of the burn (Wilgus et al. 2008, Wolfram et al. 2009, Domingo et al. 2010, Zhang etal. 2010, Atat et al. 2015, Li et al. 2016, Shpichka et al. 2019). It was reported in recent studies that epigalactocatechin gallate (EGCG) has positive effects on dendritic cells in the epidermis layer (Jeong et al. 2007, Yoneyama et al. 2008). In addition to this, in the study of Hsu et al; it was shown that EGCG and flavonoids provide the growth of keratinocytes in the epidermis layer and reactivate dying old keratonocytes (Hsu et al. 2003). Cells that migrate towards the surface of the skin normally live for about 28 days and prepare to die basically in the upper layer of the skin until the 20^th day (Hsu et al. 2003, Wilgus et al. 2008, Zhang et al. 2010, Lorenti 2012, Atat et al. 2015, Wasiak and Cleland 2015, Vinish et al. 2016, Shpichka et al. 2019, Baktir 2020). However, it was reported that epigalactocatechin gallate (EGCG), epigalactocatechin (EGC) and flavonoids activate keratonocytes in the findings. It was reported that the high amount of EGCG, catechins (EG) and flavonoids in white tea have very positive effects on keratonocytes and dendritic cells in the epidermis layer of the skin, and in addition to its properties rarely found in other protective agents, it also increases the number of collagen and reticular fibrils in the dermis and hypodermis layers of the skin (Hsu et al. 2003, Hsu 2005, Yoneyama et al. 2008, Li et al. 2016). Although it has been reported in previous studies that EGCG is mostly found in green tea, in the light of today's studies, it was reported that EGCG is mostly found in white tea, and again white tea was also shown to have a very rich content (Yoneyama et al. 2008, Islam 2011 , Oyetakinwhite et al. 2012, Kim et al. 2018, Salman and Ozdemir 2018, Yildirim etal. 2019a, Yildirim et al. 2020).

The inflammation after burn is one of the most important cellular events in the formation of cytotoxicity. Transcription factor plays a key role in the activation of genes encoding proinflammatory cytokines such as nuclear factor-kappa B (NFk-B), TNF-a and I L-1 b (Yang et al. 2014, Tsai et al. 2015, Espinosa et al. 2016). Multiple studies reported that inhibition of NF-KB transcriptional activity prevents the damage that occurs as a result of the inflammation after the burn (Yang et al. 2014, Dias et al. 2016, Espinosa et al. 2016). In addition, free oxygen radicals (SOR) formed in the skin after burns change DNA by structurally causing mutation (Bernatoniene and Kopustinskiene 2018, Cremonini et al. 2019). DNA damage and SOR accumulation causes the activation of p53 or also known as tumor protein 53 (TP53) protein (Bernatoniene and Kopustinskiene 2018). Active p53 is a transcription factor that binds to DNA by forming tetramer. The most important task of p53 controlling many genes is to employ cell DNA damage repair mechanisms by slowing down the cell cycle. If the damage cannot be repaired, it directs the cell to apoptosis (Winiarska-Mieczan 2015, Bernatoniene and Kopustinskiene 2018, Cremonini et at. 2019). 8-hydroxy-2p- deoxyguanosine (8-OHdG) in nuclear and mitochondrial DNA induced by SOR is associated with oxidative lesions and therefore it is widely used as a biomarker for oxidative stress (Chen et al. 2016, Luk et al. 2020). Although other nucleobases of DNA react similar to SOR, the 8-OHdG lesion is the most voluminous DNA lesion. Since it is relatively easily formed and promutogenic, for this reason, it is a potential biomarker of carcinogenesis (Valavanidis et al. 2009, Kawahara et al. 2010, Wang et al. 2018). Studies have shown that 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases (Wu et al. n.d., Magura and Rozhmanova 1997, Kitada et al. 2001 , Valavanidis et al. 2009, Kawahara et al. 2010, Fardid et al. 2017, Christopher et al. 2020, Kundovic et al. 2020). Intrinsic apoptosis is a cell death centered in mitochondria caused by mitochondrial outer membrane permeabilization-mediated apoptosome formation, activation of caspase-9 and subsequent activation of effector caspases (Thornberry 1998, Yang et al. 1998, Reed 2000, Galluzzi et al. 2016). Activation of caspase-3 plays an extremely important role in apoptosis among applying caspases and is accepted as a terminal event prior to cell death. Bcl-2 (B-cell lymphoma 2) prevents the effects of Bax (BCL2-associated X protein), which is a proapoptotic protein by being located in the outer membrane of mitochondria, maintains mitochondrial membrane integrity and supports cell survival. On the other hand, Bax increases mitochondrial permeability by causing both cytochrome C and SOR to be discharged from the mitochondria to the cytoplasm under oxidative stress conditions. Cytochrome C forms an apoptosome that activates caspase-3, a key regulator in the execution of apoptosis by interacting with apoptotic proteactivation factor 1 (Apaf-1) in the cytoplasm (Zhou et al. n.d., Ohta et al. 1997, Yu and Little 1998, Snigdha et al. 2012, Brentnall et al. 2013, Lopez-Furelos et al. 2016). While many mechanisms play a role in the induction of apoptosis, the most well-known mechanism has effect on DNA synthesis and repair; it was reported that it involves in the formation of reactive oxygen radicals (SOR) and initiates apoptosis through intrinsic caspases, causing mitochondrial dysfunction and stress in the endoplasmic reticulum (Zhou et al. n.d., Ohta et al. 1997, Porter and Janicke 1999, Snigdha et al. 2012, Brentnall et al. 2013). In studies, it was reported that SOR triggers the redox sensitive transcription factor nuclear factor kappa-B (NF-KB) (Romano et al. 1999, Pande and Ramos 2005, Murley etal. 2006, Lawrence 2009). Although the tissue damage mechanism varies depending on the types of burns, it was reported in the studies that increases the level of malondialdehyde (MDA) by causing lipid peroxidation and decreases the amount of antioxidant enzymes, mainly glutathione (GSH), and decreases glutathione peroxidase activity (GSH-Px), causing oxidative stress by increasing the production of free oxygen radicals (Hermans 2005, Momeni et al. 2009, Zhang et al. 2010, Lorenti 2012, Atat et al. 2015, Anthonissen et al. 2016, Bae et al. 2017, Shpichka et al. 2019, Baktir 2020). Besides, it was reported that pro-inflammatory cytokines, which play a role in inflammation in SOR tissues, increase the expression of the biomarker NF- Kb/r65 (Hermans 2005, Sakallioglu et al. 2006, Momeni et al. 2009, Zhang et al. 2010, Lorenti 2012, Builders et al. 2013, Atat et al. 2015, Anthonissen et al. 2016, Bae et al. 2017, Shpichka et al. 2019, Baktir 2020). At the same time, it was also reported that it induces apoptosis in cells due to the increase of SOR in tissues (Stallings and Lupo 2009, Wolfram et al. 2009, Arslan et al. 2012, Lorenti 2012, Shpichka et al. 2019). It was reported in studies that white tea (Camellia sinensis), which contains EGC, which is known as one of the most powerful free oxygen scavengers due to the richest number of hydroxyl groups of all teas suppresses oxidative stress by blocking the production of SOR (Almajano et al. 2008, Espinosa et al. 2014, 2016, 2016, Dias et al. 2016, Salman and Ozdemir 2018, Saral et al. 2019a, 2019b, Ylldlrlm etal. 2020).

In brief, inflammation, oxidative stress and mitochondrial dysfunction together with increasing tissue damage have an important role in the etiology of skin burns. It was mentioned in the previous data that green tea catechins prevent tissue damage by reducing inflammatory signaling mediators and upregulating anabolic mediators. Moreover, it was mentioned that green tea catechins serves for ensuring a dynamic balance between protein synthesis and degradation and increasing the synthesis of mitochondrial energy metabolism and alleviate the effects of aging. On the other hand, in a study performed by Dong Chen et al., it was set forth that EGCG contributes to the development of collagen fibrils.

In the state of the art, in addition to dressing of skin burns, costly treatment approaches such as surgical debridement, escarectomy, fasciotomy, severe fluid resuscitation, grafting, synthetic temporary closures are applied depending on the type of burn observed on the skin (1 , 2 or 3 degrees) and tissue depth. Complex treatments that are applied in addition to these treatments lead to workload on healthcare professionals, and cause losses in ergonomics of patients in their daily lives.

It is required to develop a novel wound-burn cream due to reasons such as the inadequacy of the treatments applied in wound and burn treatments in the state of the art, the existing wound-burn creams being effective only on the connective tissue, not providing an effective healing, and not having reliable ingredients.

Brief Description of the Invention and Aims of the Invention

The present invention describes a wound healing and burn cream containing white tea ("Camellia sinensis"), which has a protective effect on tissue damage. While said cream heals skin lesions after burns or physical damage, it also prevents skin wrinkles by increasing the number of collagen fibrils.

An aim of the invention is to develop a wound and burn cream that provides effective healing. The inventive cream provides an effective treatment for skin tissue damage and especially in the treatment of burns due to its healing effect on the epidermis in addition to the connective tissue.

Another aim of the invention is to provide a wound healing and burn cream that does not have a negative effect on the human health due to its natural content. The white tea extract contained in the content of the invention provides a protective effect on tissue damage formed as a result of burn. It does not cause any side effects, not only it is a natural ingredient, but also it provides an environmentally friendly content.

Another aim of the invention is to provide a cream with an anti-wrinkle formulation besides preventing skin lesions. Said wound and burn cream also has an anti-wrinkle effect in addition to healing wounds and burns. This effect is ensured by increasing the number of collagen fibrils in the connective tissue of the ingredients in the cream.

Another aim of the invention is to develop a cost efficient method for wound and burn treatment. As a result of using the wound and burn cream provided with the invention, the treatment of skin tissue damage is effectively provided, it reduces treatment costs by replacing burn intensive care and skin transplantation, which is a troublesome and expensive method.

The inventive wound healing and burn cream;

- Supports epithelial cells by strengthening the connection between skin epithelial cells, Increases the number of cells (stratum germinativum) in the reproductive layer of the skin epithelium,

Increases the synthesis of collagen and reticular fibrils in the subcutaneous connective tissue and thus the number of collagen and reticular fibrils, Induces interferon-gamma (IFN-y) secretion by acting on dendritic cells, Reduces apoptosis in epithelial cells in the skin,

- Shows the effect of reducing the production of free oxygen radicals. Detailed Description of the Invention

The present invention is a wound healing and burn cream that increases the synthesis of collagen fibrils by supporting the epithelial cells in the skin, ensures healing of skin lesions after burns or physical damage by reducing apoptosis and suppressing the production of free oxygen radicals. Cream with white tea extract contains; white tea ( Camellia sinensis) extract, saturated fatty acids, monosaturated and polyunsaturated fatty acids, vitamin E and paraffin.

Said wound healing and burn cream contains the following; 8-12% of white tea extract by weight, 8-12% of saturated fatty acids by weight, 32-36% of monounsaturated fatty acids by weight, 3-7% of polyunsaturated fatty acids by weight, 3-7% of vitamin E by weight and 33- 37% of paraffin by weight. In a preferred embodiment of the invention, said wound healing and burn cream contains the following; 10.14% of white tea extract, by weight 10.48% of saturated fatty acids by weight, 34% of monounsaturated fatty acids by weight, 5.38% of polyunsaturated fatty acids by weight, 5% of vitamin E by weight and 35% of paraffin by weight (Table 1). The white tea extract used in said cream contains 35-39% of polyphenol by weight, preferably 37.05% of polyphenol in total, but no cellulose. The white tea extract used in the country is preferably used as catechin contains; 2.89% of gallic acid by weight, 0.96% of catechin (C) by weight, 5.31% of epicatechin (EC) by weight, 74.61% of epigallocatechin gallate (EGCG) by weight and 16.23% of epicatechin gallate (ECG) by weight (Table 2). This white tea extract also contains; 0.064 ppm copper (Cu), 0.112 ppm iron (Fe), 0.65 ppm zinc (Zn), 2.47 ppm sodium (Na), 492 ppm potassium (K), 14.51 ppm calcium (Ca), 311 ppm manganese (Mn), 69.3 ppm magnesium (Mg,), 1.59 ppm aluminum (Al) (Table 3). Table 1. Content analysis of wound healing and burn cream ( 100 mg by weight).

Table 2. White tea extract total catechin content analysis (100mg by dry weight).

Table 3. White tea extract mineral content analysis

10

The polyphenols, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids and vitamin E contained in the cream have the effect of reducing free oxygen radicals by reducing the apoptosis in the epithelial cells of the skin. The iron, copper and manganese contained in white tea extract increase the number of collagen and reticular fibrils in the subcutaneous connective tissue. The aluminum content included in the ingredient exhibits an antiseptic effect; while zinc has an antiseptic effect, it also strengthens the connection between skin epithelial cells. Paraffin content also provides an antiseptic effect to the cream.

Said cream contains 2-3% catechin in total. Catechins are natural antioxidants that assist in preventing the cell damage. Catechin can reduce the formation of free radicals in the body and protect cells and molecules against radical damage. It is known that free radicals play a role in accelerating the aging process. EGCG (Epigallocatechin Gallate) is one of the most powerful compounds found in "green tea". EGCG and EGC from these catechins from white tea extract increase the number of the productive layer (stratum germinativum) in the skin epithelium, increase the number of collagen and reticular fibrils in subcutaneous connective tissue, inhibits the antigen presenting mechanism of dendritic cells. At the same time, these catechins have the effect of reducing free oxygen radicals by reducing apoptosis in epithelial cells in the skin.

In the present invention; the most suitable extract was obtained by analyzing the brewed, dried, wet extracts and their catechin groups and mineral contents by HPLC analysis (Tables 1-4) so as to examine the protective and therapeutic effects of white tea extract against physiological aging or physical and chemical trauma, skin clinical correlations due to skin burns.

Burn cream prototype is obtained with its ingredients by mixing the obtained extract, white tea extract previously obtained with natural methods with the cream that is previously designed and contains alkali esters (72%), free fatty acids (14%), hydrocarbons (11%), free alcohols (1%), oleic acid, paraffin, stearic acid, vitamin E and neutral saturated fat (with a ratio of 3% white tea extract in total volume).

For the cream formulation obtained in the invention; - various HPLC, mineral, catechin groups (such as EC, EGC, EGCG ...) and flavonoids and other chemical analysis,

- microbiological tests (such as Eosin Methylen Blue Agar, Blood Agar, Chocolate Agar, Saboraud-Dextrose Agar etc.)

- tests regarding the determination of the correct packaging technology to increase the shelf life of the product and determination of preservatives based on the selected packaging type (antifungal, bacteriocitatic agents), were carried out.

The wound healing and burn cream with white tea extract can also be used so as to prevent wrinkles by increasing the number of collagen fibrils in the connective tissue with the ingredients therein.

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Claims

1. A wound healing and burn cream that increases the synthesis of collagen fibrils by supporting the epithelial cells in the skin, ensures healing of skin lesions after burns or physical damage by reducing apoptosis and suppresses the production of free oxygen radicals, characterized in that, it comprises; 8-12% of white tea (Camellia sinensis) extract, 8-12% of saturated fatty acids by weight, 32-36% of monounsaturated fatty acids by weight, 3-7% of polyunsaturated fatty acids by weight, 3-7% of vitamin E by weight and 33-37% of paraffin by weight.

2. A cream according to claim 1 , characterized in that; it contains 10.14% of white tea extract by weight, 10.48% of saturated fatty acids by weight, 34% of monounsaturated fatty acids by weight, 5.38% of polyunsaturated fatty acids by weight, 5% of vitamin E by weight and 35% of paraffin by weight.

3. A cream according to claim 1 , characterized in that; the white tea extract contains 37.05% of polyphenol by weight in total.

4. A cream according to claim 1 , characterized in that; the white tea extract comprises the following as catechin; contains 2.89% of gallic acid by weight, 0.96% of catechin (C) by weight, 5.31% of epicatechin (EC) by weight, 74.61% of epigallocatechin gallate (EGCG) by weight and 16.23% of epicatechin gallate (ECG) by weight.

5. A cream according to claim 1 , characterized in that; white tea extract contains; 0.064 ppm copper (Cu), 0.112 ppm iron (Fe), 0.65 ppm zinc (Zn), 2.47 ppm sodium (Na), 492 ppm potassium (K), 14.51 ppm calcium (Ca), 311 ppm manganese (Mn), 69.3 ppm magnesium (Mg,), 1.59 ppm aluminum (Al).

6. A cream according to any of the preceding claims, characterized in that; it contains white tea extract with anti-wrinkle effect.

7. A cream to be used for preventing wrinkles characterized by comprising the following; 8-12% of white tea (Camellia sinensis) extract, 8-12% of saturated fatty acids by weight, 32-36% of monounsaturated fatty acids by weight, 3-7% of polyunsaturated fatty acids by weight, 3-7% of vitamin E by weight and 33-37% of paraffin by weight.