GB2562991A

GB2562991A - 4-N butylresorcinol in a skincare formulation in concentrations of twenty percent, up to and including sixty percent

Info

Publication number: GB2562991A
Application number: GB1702690.7A
Authority: GB
Inventors: Laura Echeverria Natalie
Original assignee: Asaya Cosmeceuticals
Current assignee: Asaya Cosmeceuticals
Priority date: 2017-02-20
Filing date: 2017-02-20
Publication date: 2018-12-05
Also published as: GB201909518D0; GB201702690D0; WO2018150395A3; WO2018150395A4; WO2018150395A2

Abstract

A skincare formulation may be in the form of a paste, gel or cream and may contain 4-N-Butylresorcinol in varying overall percentages between sixty and twenty per cent. It may be used to treat various hyper-pigmentary skin disorders including acne vulgaris and atrophic scarring. It may be used as a peel. It may be used in conjunction with a dietary regime to treat, amongst others, Melasma.

Description

This invention relates to 4-n- butylresorcinol in a skin care formulation using concentrations of twenty percent up to and including sixty percent. Skin care formulations include pastes, gels, lotions and creams. These preparations are to be used as a peel to treat hyperpigmentary skin disorders, including melasma, post-inflammatory hyperpigmentation and solar lentigines. In addition, these preparations are to be used to treat acne vulgaris, atrophic and hypertrophic scars and as an anti-aging treatment.

Background

Hyperpigmentation is a common skin disorder, involving the hyperactivity of epidermal melanocytes. Areas of the face develop dark patches of hyperpigmentated skin, causing great distress to patients.

The treatment for melasma is challenging, due to its' complex and multifarious diagnoses. Addison's disease, Cushing's disease, sun exposure, pregnancy, oral contraceptives, antiepilepsy drugs and other medicaments, are thought to be possible causes.

Melanogenesis involves melanocytes and surrounding keratinocytes. The melanin pigment is a polymer, which is created within the melanosomes and is synthesised from the amino acid l-tyrosine, which is converted by the enzyme tyrosinase to dopaquinone. Three histological pigmentation patterns have been identified: epidermal, whereby the pigment is deposited in the basal or supra basal layer; dermal, in the superficial and mid-dermis; and mixed, which is characterized by features of both the epidermal, and the dermal patterns. Hypermelanosis may be epidermal (brown), dermal (blue-grey), or mixed (brown-grey).

Acne vulgaris is a common skin concern, which primarily affects adolescents and young adults. Various hypotheses exist, but the definitive cause is yet to be established. The pathogenesis of acne is attributed to an increase in sebum production, sebum lipids, androgen activity and bacteria such as Propionibacterium acnes. Subsequent atrophic or hypertrophic scarring is common,

A scar is broadly characterised as the increase of tissue formation or damage to tissue. Scar formation is a natural part of the healing process. Wound healing includes fibroblast proliferation to create collagen, inflammation, granulation and extracellular matrix remodelling. Treatment of wounds with an emphasis on minimal formation of fibrous tissue, involves infection control, hydration, anti-inflammatories, inhibition of collagen synthesis, growth factor (TGF-b) inhibition, calcium antagonists such as magnesium, protein kinase (PKC) inhibition and tyrosine kinase inhibitors.

Anti-aging skincare involves, sun protection, anti-oxidants to combat oxidative stress caused by free radicals, hydration, exfoliation, stimulation of ceramide levels and maintenance at a cellular level, to promote fibroblast production of collagen, keratinocyte production of keratin and tropoelastin for the maintenance of elastin.

The use of peels as a skin treatment dates back to ancient times. Peels, especially superficial and medium depth peels are effective treatment modalities for multiple skin disorders, such as hyperpigmentation, acne, scars and wrinkles; in addition, peels resurface and stimulate cell renewal, to improve the appearance of skin. Peels are the controlled destruction and regeneration of tissue. Peels containing resorcinol, a phenolic derivative, such as Jessner's solution and modified Unna's paste are widely used and provide good results.

4-N-Butylresorcinol is both a phenol and resorcinol derivative inhibiting both tyrosinase and tyrosinase related protein TRP1. 4-N-Butylresorcinol has a strong protective effect against H202 induced DNA damage and is shown to have anti-glycation effects with no cytotoxicity. This invention relates to the use of 4-n-butylresorcinol using concentrations of 20% up to and including 60% as a peel treatment for melasma, acne, hypertrophic and atrophic scars and as an anti-aging treatment.

Summary Of In Vivo Study - Melasma

Participants

Eighty five women, between the ages of 32 - 45, exhibited the following symptoms, thick coating on tongue, lethargy, bloated abdomen, thick vaginal discharge with unpleasant odour, low mood, irritability, joint pains, muscle aches and dermal and epidermal melasma. Examination with Wood's lamp distinguished dermal and epidermal melasma. The degree of severity of melasma was evaluated by the use of the MASI scoring system. Food allergen test revealed gluten and or yeast intolerance.

Aim

To determine over production of melanin as a result of food allergen and assess efficacy of melasma treatment plan.

Forty women were given a healthy gluten free and or yeast free diet plan for six months. The remaining participants began our melasma treatment plan. Six medium depth peels were administered at two weekly intervals, followed by four mild peels with skin plate at two weekly intervals and four mild peels at weekly intervals. Participants were advised not to use any other skincare products during the treatment plan. A sun protection cream was provided, plus all participants received our wound healing ointment. The forty women following a gluten yeast free diet for six months remained on the diet and began the melasma treatment plan. The entire process was replicated. All participants tolerated the melasma treatment well with no reported side effects.

The study was undertaken in compliance with Good Clinical Practice (GCP) and in adherence to Good Manufacturing Practice (GMP). All participants were previously resistant to other modes of treatment with recurrence. Any individual meeting the following criteria was excluded from the study:

Pregnant, breastfeeding, skin infections such as herpes simplex virus, keloid formation, skin cancer, collagen vascular disease, bleeding disorder and no use of retinoids or other hypopigmentating treatments six months prior to enrolment on to the study.

Table 1. Results

Group	Evaluation	Evaluation	Evaluation	Evaluation

Gluten / Yeast Free Diet	0	0	0	0
Regular Diet	0/1	0/1/2	2/3/4	3/4

= Normal Skin Colour, 1 = Barely Visible, 2 = Mild Hyperpigmentation, 3 = Moderate Hyperpigmentation, 4 = Severe Hyperpigmentation.

The results outlined in Table 1. demonstrate the efficacy of 4-n-butylresorcinol in a peel composition as an effective treatment to combat both dermal and epidermal melasma. Furthermore, it is apparent that a group of people diagnosed with dermal and epidermal melasma over produce melanin as a protective mechanism against the toxic effects of a gluten and or yeast food allergy.

More studies are required to ascertain whether an impediment to homeostasis via other food allergies, toxic substances or nutritional imbalances, not excluding hormonal imbalances, are further possible causes in an individual diagnosed with melasma.

Data gathered during the eighteen month period post melasma treatment, revealed further positive outcomes. Independent examinations confirmed marked improvement in unrelated skin disorders, notably acne vulgaris and atrophic scars. Overall improvement in the appearance of skin with increase of collagen and significant improvement in global firmness and jaw-line contour was also observed. Revisions to the original formula were developed and distinct compositions were devised respectively.

Preliminary observations were conducted based upon these new compositions. The study models albeit small exhibited substantive results. The findings from these initial examinations revealed a vast reduction in the prevalence of nodulocystic acne. The appearance of scars such as rolling, ice pick, punched and boxcar scars of depths graded as macular, mild, moderate and severe were dramatically improved. Even more remarkable were the results attained from the treatment of hypertrophic and atrophic post operative scars, whereby scars were barely visible after only four applications. The anti-aging treatment demonstrated a significant reduction in wrinkles, pores were minimised, elasticity measured by cutometry was greatly improved, ceramide levels were increased with decreased transepidermal loss and increase of type I III V collagen.

These preliminary findings along with the compositions for acne vulgaris, anti-aging, scars and wound healing are to be assigned to an independent body to perform independent thorough quantitative clinical trials. A comprehensive insight will provide a full appreciation of the compositions and their integral roles, respectively. At this stage, disclosure by what method efficacy is achieved would be entirely speculative and misleading. Hence, these compositions are omitted from this section of the patent literature, on the grounds that the compositions and the results pertaining to these compositions do not form part of the patent and are for reference purposes, only. Upon completion of the aforementioned studies, a summary of the results along with the compositions shall be included within this section.

Conclusion

Hydroquinone is regarded as the gold standard ingredient for the treatment of hyperpigmentation; however, it is not useful in altering the colour of melanin that is previously present in the dermis and epidermis. Furthermore, due to the risks of side effects it has been banned European Committee (24^th Dir 2000/6/EC) and is available via prescription, only. Nine years of research has determined 4-N-Butylresorcinol as a superior treatment modality when used in high concentrations of twenty percent up to and including sixty percent. The results from the melasma study illustrate use of 4-n-butylresorcinol as a peeling agent in high concentrations as an effective treatment to combat melasma, with no concerns regarding cytotoxicity. This novel approach to the use of 4-n-butylresorcinol offers a distinct advantage, by combining the properties of 4-n-butylresorcinol as a potent tyrosinase and TRP 1 inhibitor with its ability to perform as a peeling agent, to both treat and peel multiple layers of the skin simultaneously, which is especially beneficial for the treatment of dermal melasma. The advantages of 4-n-butylresorcinol as a peeling agent extending beyond the treatment of hyperpigmentary skin disorders have only just been discovered. Further studies into 4-n-butylresorcinol will reveal its multifarious benefits as a treatment for acne vulgaris, atrophic and hypertrophic scars and as an anti-aging treatment.

Melasma Treatment

The first stage of the treatment for melasma must include an individualistic approach to establish the cause. It is imperative that tests be carried out to detect any food allergies, toxic substances such as high levels of heavy metals, nutritional imbalances and hormonal imbalances. If a food allergy and or toxic substance are present, this element of the diet is removed and the process of accelerated elimination may begin. The Perque detox program, followed by an uptake of organic spirulina, organic sulphur, mineral pitch (Shilajit) and Zechstein Sea magnesium oil. The amount of time it takes for substances to be completely dispelled from the body, is on average three to six months. Hormonal imbalances and or thyroid concerns are to be treated by an alternative medicine practitioner who can prescribe a tailored natural composition. Once the symptoms are alleviated stage two of the treatment may commence with the introduction to the generic diet.

A generic diet with the aid of supplementation has been developed targeting busy households. The diet is quick and easy and covers every aspect of the functions of the body 'homeostasis maintenance'. To follow is a list of supplements which form part of this diet:

Saffron, white willow bark, golden root (Rhodiola Rosea), organic sulphur, spirulina, mineral pitch (Shilajit), R-lipoic acid, L-citrulline, Chinese senega root (Polygala Tenuifolia), white spruce (Picea Glauca), zinc (Opti), biotin, KSM-66 ashwagandha, pomegranate seed, ubiquinol CoQlO, astaxanthin, sumac bran, niacinamide, 5HTP, BCM-95 bio-curcumin, Moringa Oleifera, noni, lion's mane (Hericium Erinaceus), L-theanine (suntheanine), xanthohumol (luciden form), Eucommia Ulmoides, camu camu, eleuthero, kelp, raspberry seed, hemp seed and Boswellia Serrata.

The supplements are for adult use only. Instructions on how to use these supplements accompany the menu for breakfast, lunch and dinner. The third and final stage of the treatment is a course of topical peels, influencing distinct steps of melanin synthesis.

Preparation

1. A blend of organic oils to remove make-up.

2. A cleansing water made of crystal water, megahydrate powder, papaya and Moringa Oleifera.

3. Skin plate of pure DMSO bathed in organic aloe cape stem cells without aloin.

Melasma Peel

To follow is a list of the ingredients used to influence distinct steps of melanin synthesis:

1. 4-N-Butylresorcinol - Tyrosinase inhibitor, TRP1 inhibitor.

2. Resveratrol of Japanese Knotweed -TRP2 inhibitor, TGF Beta inhibitor.

3. Curcumin of Turmeric - Protein Kinase C inhibitor, Alpha MSH inhibitor.

4. Fucoidan of Kelp - Autophagy, TGF Betal inhibitor.

5. Sulphur- Glutathione optimisation.

6. White willow bark - Anti-Inflammatory.

7. Ellagic Acid of Pomegranate - Copper chelation.

8. Niacinamide - Melanosome transfer inhibitor.

9. Ferulic Acid of Angelica Sinensis - Tyrosine oxidation inhibitor.

Post Peel Treatment

Peel is left on face for approximately 45 minutes. Face is washed using water cleanser.

1. Organic aloe cape stem cells ointment.

2. Organic healing balm.

3. Organic tinted sun protection lotion.

1. A medical or cosmetic formulation comprising 4-n-butylresorcinol in a concentration greater than substantially 18%.

2. A formulation as claimed in claim 1, in which said concentration is between substantially 20% and substantially 60%

02 18

Claims

Amendments to the claims have been made as follows:

20 04 18

Claims

1. A skin formulation of a peel, spray, paste, gel, lotion, serum, cream.
2. A medical or cosmetic skin formulation comprising 4-n-butylresorcinol in a concentration greater than substantially 18%.
3. A formulation as claimed in claim 2, in which said concentration is between substantially 20% and substantially 60%.
4. A formulation as claimed in any preceding claim, for use in a treatment to produce a mild peel.
5. A formulation as claimed in any preceding claim, for use in a treatment to produce a medium peel.
6. A formulation as claimed in any preceding claim, for use in a treatment to produce a deep peel.
7. A formulation as claimed in any preceding claim, for use in the treatment of hyperpigmentory skin disorders.
8. A formulation as claimed in any preceding claim, for use in the treatment of acne vulgaris.
9. A formulation as claimed in any preceding claim, for use in an anti-aging treatment.
10. A formulation as claimed in any preceding claim, for use in the treatment of any one or more of the group comprising complexion: pore size, skin density, hydration.
11. A formulation as claimed in any preceding claim, for use in the treatment of facial hypertrophic and atrophic scars.
12. A formulation as claimed in any preceding claim, for use in the treatment of hypertrophic and atrophic scars of the body.
13. A formulation as claimed in any preceding claim, for use in the treatment of post-operative hypertrophic and atrophic scars.
14. A formulation as claimed in any preceding claim, diluted with a hydrophilic agent, or any diluent known in the art.
15. A formulation as claimed in any preceding claim, with a preservative such as levulinic acid, or any other preservative known in the art.
16. A formulation as claimed in any preceding claim, without a preservative.
17. A formulation as claimed in any preceding claim, using any delivery system, such as liposomal delivery systems and all agents to aide penetration of the epidermis, known in the art.
18. A formulation as claimed in any preceding claim, comprising any one or more of the ingredients mentioned herein for the treatment of hyperpigmentation.
19. A formulation as claimed in any preceding claim, comprising any one or more of the ingredients mentioned herein for the treatment of melasma.
20. A formulation as claimed in any preceding claim, comprising any one or more of the following ingredients: DMSO, levulinic acid, fatty acids such as oleic acid, coconut oil, sources of vitamin C, e.g. rosehip seed, camu camu, infection control such as natural antibiotics e.g. colloidal silver, hydration agents such as glycerin and hyaluronic acid, walnuts, opti zinc, inhibition of collagen synthesis, healing agents such as croton lechleri, tyrosine kinase inhibitors, calcium antagonists such as magnesium, antioxidants such as r lipoic acid, astaxanthin and ubiquinol coqlO, telomeres lengthening agents such as resveratrol and cycloastrogenol, TGF-b inhibitors, protein kinase C (PKC) inhibitors, scar reduction agents such as niacinamide, antiinflammatories such as white willow bark, bamboo, cannabinoids, watermelon skin, agents for collagen stimulation, anti-glycation, immune pathways, red spinach, cherry blossom, tormentil, chitin, rambutan, amino acids, (GL1), (GL3), (TTG1), soursop, oleuropein, cassia, apple skin, osmanthus and all anti-aging agents known in the art.