Invented by Jose Carlos Garcia-Garcia, Jeffrey Alan Henry, Brian W. Howard, Nicholas William Geary, Raul Victorino Nunes, Freddy Arthur Barnabas, Safa MOTLAGH, Yiping Sun, Procter and Gamble Co

The market for compositions and methods to improve skin health has seen significant growth in recent years. With an increasing emphasis on self-care and personal well-being, consumers are becoming more conscious about the health and appearance of their skin. This has led to a surge in demand for products and treatments that can enhance skin health and address various skin concerns. One of the key drivers of this market growth is the rising awareness about the damaging effects of environmental factors such as pollution, UV radiation, and stress on the skin. These factors can lead to premature aging, dullness, dryness, and other skin issues. As a result, consumers are actively seeking out compositions and methods that can protect and nourish their skin. In response to this demand, the skincare industry has witnessed a proliferation of innovative compositions and methods that claim to improve skin health. These products range from topical creams, serums, and masks to advanced treatments like laser therapy, chemical peels, and microdermabrasion. Additionally, there has been a surge in the popularity of natural and organic skincare products, as consumers are increasingly concerned about the potential side effects of synthetic ingredients. One of the key trends in the market is the use of active ingredients that have been scientifically proven to benefit the skin. Ingredients like hyaluronic acid, retinol, vitamin C, and peptides have gained popularity due to their ability to hydrate, rejuvenate, and promote collagen production in the skin. These ingredients are often incorporated into compositions such as serums and creams, which are designed to target specific skin concerns like wrinkles, hyperpigmentation, and acne. Another emerging trend in the market is the use of innovative delivery systems that enhance the efficacy of skincare compositions. For example, encapsulation technology allows active ingredients to be delivered deep into the skin, ensuring better absorption and results. Similarly, transdermal patches and microneedling devices are gaining popularity as they facilitate the penetration of ingredients into the skin’s deeper layers. Furthermore, the market for compositions and methods to improve skin health is not limited to topical products alone. Nutritional supplements that claim to promote healthy skin from within have also gained traction. These supplements often contain vitamins, minerals, antioxidants, and other nutrients that support skin health and address specific concerns like acne, inflammation, and dryness. However, it is important to note that while the market for compositions and methods to improve skin health is thriving, consumers should exercise caution and do thorough research before investing in any product or treatment. With the abundance of options available, it can be overwhelming to choose the right one. Consulting with a dermatologist or skincare professional can help individuals make informed decisions based on their specific skin type and concerns. In conclusion, the market for compositions and methods to improve skin health is experiencing rapid growth due to increasing consumer awareness and demand. With a wide range of products and treatments available, individuals have more options than ever to address their skin concerns and achieve healthier, more radiant skin. However, it is crucial to approach this market with caution and seek professional advice to ensure the best results.

The Procter and Gamble Co invention works as follows

The disclosure is about topical compositions and method that contain whole, non-viable Micrococcaceae cell, which have been processed in a way to minimize lysis while killing the cells. Topical compositions and techniques are effective for decreasing skin inflammation, and improving skin barrier functions.

Background for Compositions and methods to improve skin health

Skin barrier function is important for skin health as it protects against external chemical and biological threats. The skin reduces the penetration of harmful radiations, such as ultraviolet (UV), into deeper layers of the skin and helps to prevent infection. The skin also serves as a barrier to prevent moisture loss and acts as a permeability. Skin barrier dysfunction can cause chronic skin conditions and disease. In extreme cases, it can threaten the viability or the organism.

The U.S. Patent Publication Nos. 20140335137 and 20140186433 describe a topical composition containing extracts of bacteria. “Topical compositions comprising extracts from bacteria have been described (see U.S. Patent Publication Nos. Compositions for sun-damaged tissue have used extracts from Micrococcus, which contain endonuclease (a DNA repair enzyme). Cells are lysed in order to release intracellular endonuclease. The lysate is then collected and added to compositions. The lysis of cells can be accomplished by a variety of methods. These include heat, chemicals, enzymes, ultrasound, physical stress, (e.g. pressure, homogenization or mechanical disruption, freeze/thaw cycles), radiation, (e.g. gamma and ultraviolet), viral infection, lytic expression, as well as other known techniques. These methods of lysing the cells break down the bacterial cell walls and the cell’s basic structure. The lysed cell wall and other structural components are typically separated from the endonuclease-containing portion of the lysate and discarded. The compositions containing live Micrococcus luteus were also described in U.S. Patent Publication No. 20110189133). Micrococcus luteus live cultures can compete against other skin flora in order to treat or prevent skin conditions associated with unwanted bacteria growth. “However, delivering live organisms directly to the skin is challenging, both from a formulation standpoint and a safety perspective, particularly in compromised skin.

Inflammation, and the disruption of homeostasis that it causes, can reduce skin barrier function. During an inflammatory reaction, immune cells (e.g. lymphocytes, macrophages, keratinocytes, etc.) and skin cells release cytokines. These cytokines can be either pro-inflammatory or anti-inflammatory. Compositions and methods to regulate cytokine release in order to treat and prevent inflammation have a positive impact on the skin barrier function as well as overall skin health. These are ongoing objectives for the personal care industry.

The disclosure is about compositions and methods to improve skin health and appearance, including applying whole, nonviable Micrococcaceae cell to the skin.

In one aspect, this disclosure discloses a topical formulation containing whole, non-viable Micrococcaceae cell. The Micrococcaceae cell have been treated to minimize lysis and kill the cells. The topical composition can also include other non-viable Gram positive bacteria cells from the family Micrococcaceae such as bacteria of the genus Kocuria. The topical composition may also include a skin care ingredient selected from the following: an antiinflammatory agent; a probiotic; a probiotic derived agent; a sunscreen/sunblock agent; an antiacne or anti-cellulite product, such as a Kocuria bacteria cell.

In another aspect, a method for reducing skin inflammation is disclosed. This involves applying a composition containing whole, non-viable Micrococcaceae to the skin. The composition described herein reduces, in one aspect, IL-1Ra/IL-1? In comparison to skin that has not been treated or skin that has been treated with Micrococcaceae live cells or lysed, the composition described herein decreases the ratio of IL-1Ra to IL-1? The composition described in this application also decreases the ratio between IL-1Ra and IL-1? In comparison to skin that has not been treated or skin that has been treated with Micrococcaceae live cells or lysed Micrococcaceae, the composition described herein decreases the ratio of IL-1Ra to IL-1? In other embodiments, the composition reduces the redness of skin following skin damage. In certain embodiments, the composition can improve skin health and appearance by, for example, improving the barrier function, increasing moisture content, or decreasing irritation.

The disclosure, in one aspect, provides a method for increasing the anti-inflammatory activities of a population Micrococcaceae cell by processing the cells into whole, nonviable cells. In certain embodiments, processed cells reduce IL-12p70 and/or increase IL-10 by Peripheral Blood Mononuclear Cells in vitro. This increases the ratio of IL-10/IL-12p70 for PBMCs that are exposed to whole non-viable Micrococcaceae. The disclosure also provides a way to select bacterial modulators for skin barrier health that can be used in topical formulations, based on the ability of these bacteria to influence specific biomarkers in vitro. In one aspect, bacteria are chosen for their ability in a PBMC inflammation model to increase or maintain IL-10 and/or decrease IL-12p70.

In some embodiments, Micrococcaceae cell compositions or populations are composed of Micrococcaceae from the genera Micrococcus and Kocuria. Optionally, they may be from Micrococcus varians, Micrococcus varians, Micrococcus Lylae, Kocuria Kristinae or Kocuria Rhizophila. In some embodiments the composition or the population of Micrococcaceae cell includes cells from at least one Micrococcus-luteus strain, selected from the group consisting NRRLB-67034 and B-67033 and strains identified 3C,133C,173C,157C,183C,66C,55C,50C,119C and 60C.

The following detailed description and the accompanying drawings will reveal other features and benefits of the disclosure. The detailed description, including the examples, is provided only as an illustration. This is because the detailed descriptions and specific examples are intended to illustrate the preferred embodiments.

The disclosure provides methods to improve skin health by topically applying a formulation containing whole, non-viable Micrococcaceae cell to the skin. The disclosure relates also to methods for increasing the anti-inflammatory properties of Micrococcaceae and other Gram-positive bacteria cell, which include processing the cells using heat, chemicals and/or radio waves to produce non-viable, whole cells. The disclosure also provides topical formulations that contain whole, nonviable Micrococcaceae cell. The disclosure also provides a way to select bacterial modulators for skin barrier health based on their ability to influence specific in vitro markers, such as the ratio IL-10/IL-12p70 that is produced by PBMC.

The disclosure relates to non-viable, whole Micrococcaceae cell that has been processed so as to minimize lysis while killing the cells. Unexpectedly, it was found that non-viable Micrococcaceae whole cells had a stronger anti-inflammatory effect than living Micrococcaceae (FIG. 1A). The whole, non-viable Micrococcaceae cells also have anti-inflammatory effects that are more pronounced than lysed or disrupted Micrococcaceae cells, such as cells processed using a French press, bead-beating or extreme chemistries (e.g., CTAC (Hexadecyltrimethylammonium chloride), or CTAB (Hexadecyltrimethylammonium bromide), which are examples of cationic surfactants). These processing effects are dependent on time and concentration and can be optimized for maximum efficacy, without destroying the cells. “It will be understood that the Micrococcaceae cell aspects of various embodiments described in the present invention also apply to Micrococcaceae cell aspects of various embodiments described in the present invention.

In one aspect, Micrococcaceae cell of the composition or method comprises cells belonging to the genera Micrococcus or Kocuria. For example, Micrococcus varians, Kocuria variable, Kocuria varians, Kocuria variants, Kocuria-lylae, Micrococcus-luteus, Kocuria-rhizophila, Kocuria-lylae, and combinations thereof. Micrococcaceae Cells of the Composition or Method are at least one Micrococcus Luteus strain, selected, but not restricted to, NRRLB-67034 and NRRLB-67033 and strains identified within our internal library, as 66C 55C 243C 50C 59C 3C 133C 157C and 183C. In certain embodiments, Micrococcaceae cell of the composition or the method are cells from Micrococcus B-67034 strain or strain B-67033. In certain embodiments, the non-viable Micrococcaceae cell (including the ones listed above) is selected to be used in the compositions or methods of the disclosure based upon their ability in an in vitro screen assay (e.g. PBMC assay) to demonstrate anti-inflammatory capability.

The following definitions can be helpful to the skilled practitioner when attempting to understand the disclosure. The meanings of scientific and technical words used in the disclosure are those that would be understood by a person with ordinary skill in their art.

The term “apply” is used. The terms ‘apply? “A topical composition” is referred to as a composition when it is used in this document.

The term “dermatologically accepted” is used herein to refer to a composition or component thereof that can be used in contact with mammalian skin tissue without undue toxicity, incompatibility, instability, allergic response and the like. As used herein, the term “dermatologically acceptable” refers to a component or composition that can be used on mammalian tissue without causing undue toxicity. The term “dermatologically accepted carrier” is used. The term “dermatologically acceptable carrier” is used in this document to refer to a carrier which is suitable for application on keratinous tissues, has acceptable aesthetic qualities, is compatible with active compounds and does not pose any safety or toxic concerns.

The term “effective amount” is used to describe the effective amount. “The terms ‘effective amount? As used herein, the term refers to a quantity of a compound, or composition, sufficient to produce a positive effect without serious side effects.

The term “facial skin surface” as used herein refers to one or more of the forehead, peri-orbital, cheeks and peri-oral skin surfaces. As used herein, the term “facial skin surfaces” refers to any or all of the following: forehead, periorbital (the area between the eyebrows), cheek, perioral, chin and neck.

The term “improving skin health” is used here. As used herein, the term “improving skin health” refers to a positive change in appearance, texture and/or functionality of skin. Perceptible benefits or changes can include: “Preventing or reducing inflammation, improving skin barrier functions, reducing skin redness/irritation, reducing the appearances of wrinkles, deep crevices or fine lines, bumps or blemishes; reducing the appearances of large pores, or crevices; thickening keratinous tissues; increasing collagen and/or skin elasticity, improving coloration, such as reducing dark circles under the eyes, blotchiness or dullness, increasing s

The term “?lyse” As used herein, the term ‘lyse’ refers to breaking or perforating a cell or structural component (e.g. cell wall, membrane or cytoskeleton). Lysed cells lose their characteristic shape (e.g. spherical, elliptical), and/or all or some of their soluble intracellular content. The term “minimizing lysis” is used. Refers to the processing of a population of cell in such a way that only a subset is lysed (e.g. less than 25%) and the rest of the population remains whole.

The term “non-viable” is used here to refer to a cell that is not reproducing, i.e., it’s not capable of reproduction. As used in this document, the term “non-viable” refers to a non-reproducing cell, that is, one which is incapable of reproducing. It is possible to confirm the presence of non-viable cell using techniques known in this art. For example, a colony formation assay can be used to determine colony form units (CFUs) per unit (milligrams, milliliters, etc.). Or dyes that differentially color live and dead cell.

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