WO2021257009A1 - A drug-free antibacterial lotion - Google Patents

A drug-free antibacterial lotion Download PDF

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Publication number
WO2021257009A1
WO2021257009A1 PCT/TR2020/000008 TR2020000008W WO2021257009A1 WO 2021257009 A1 WO2021257009 A1 WO 2021257009A1 TR 2020000008 W TR2020000008 W TR 2020000008W WO 2021257009 A1 WO2021257009 A1 WO 2021257009A1
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WO
WIPO (PCT)
Prior art keywords
acne
niacinamide
skin
sodium chloride
lotion
Prior art date
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PCT/TR2020/000008
Other languages
French (fr)
Inventor
Fatma Gulru ERDOGAN
Original Assignee
Erdogan Fatma Gulru
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Publication date
Application filed by Erdogan Fatma Gulru filed Critical Erdogan Fatma Gulru
Priority to PCT/TR2020/000008 priority Critical patent/WO2021257009A1/en
Publication of WO2021257009A1 publication Critical patent/WO2021257009A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/14Alkali metal chlorides; Alkaline earth metal chlorides

Definitions

  • the invention relates to a drug -free lotion, against which a resistance Is not developed, for the freetment of the bacterial skin lessons and active acne lesions without causing skin dehydration, which may he used for everyone including pregnant women and children of ell ages and may he formed by using niacinamide together with sodium chloride of specified ratios and/or pantothenic acid of specified ratios, wherein the drug- free lotion of the invention may be applied easily on the oily skin end acts in a short period of time such as few days upon contact for 10-15 minutes par day,
  • the invention is a lotion, against which a resistance is not developed, which does not contain a drug and/or an antibiotic and thus is available overdhmcounter, wherein said lotion may be used safely in pregnant woman and children of all ages for the prevention or treatment of lesions that develop with the effect or contribution of bacteria on the skin surface, such as acne, folliculitis, etc,
  • Antibiotic end antiseptic resistance is an Increasing problem during recent years (Reference 1). Accordingly, formulations that are net antibiotics, antiseptic and drugs but have an antibacterial efficacy will continue to remain on the agenda.
  • Said invention relates to a public access, first-line antibacterial formulation, an efficacy on the bacteria of which has been demonstrated, which formulation Is cost-effective, easy to prepare and cheap, wherein said formulation is not a drug, thus, a resistance against its mechanical impact Is difficult to develop, wherein said efficacy does not contain an enzymatic step, an immunological reaction, etc,
  • formulations are restricted due to the active ingredients and the like, which has an antibacterial efficacy but Is difficult and laborious to reach, or is expensive, rare and found In some parts of the world. Therefore, organic, easy-to-find, cost-effective materials that will not force people financially are used in the formulation of the invention.
  • an antibacterial formulation is presented in the patent document CN108522S47 titled ’'anti bacterial care solution composition and application thereof, but the formulation contains an extract of “taxes ehinensis (Chinese yew ⁇ ’*, in our formula, local and hsrd-to-find substances are not used.
  • the substances selected for our formulation are organic substances that have no drug affects and are easily available, and era created by the combination of effective and safe concentrations. Each of them Is organic antibacterial non- drug substances. The most important reason for forming a composition is to prevent the development of antibacterial resistance and to strengthen the effect (references
  • the patient usually has oily skin, and the agents used to remove this oil may cause excessive drying of skin, in addition, if is known that a large variety and number of microorganisms are produced In an oily secretion medium, called sebum, which facilitates the growth of seme bacteria on this oily skin surface, Especially, Cutibactehum acoes has a particular important place among the causes of acne.
  • the treatment agents (such as combinations containing different acids, alcohol ⁇ soluble formulae) given for drying the lesions quickly may causa Irritation, redness and burning on the skin.
  • the treatment agents that do not cause Irritation and redness on the skin have limited success in drying up the lesions or preventing the lesions from developing.
  • An ideal agent for the none treatment should provide a alight exfoliation while mosstening the skin to ensure the exfoliation net to be seen and also should rapidly dry the developing lesions before growing without causing any irritation, redness, burning, it should also nourish the skin and prevent it from getting thinner, in addition, they should be able to ba used easily by the patients at child bearing age, or pregnant patients or breastfeeding patients. It should not be a drug, ft should be used safely and comfortably at any age, and It should also be cost effective, i.e. not he expensive and not contain substances that are difficult to find
  • Benzoyl peroxide This Is on agent which may be used frequently, have side effects such as redness, burning and irritation on the akin, be considered as a drug and have no skin nourishing end moistening property,
  • Salicylic ⁇ acid This is an agent which may be considered as a drug and is Intended to be used for exfoliating the skin and drying the lesions. It is comedoiytic and one of the most used agents for the acne treatment. The pregnancy category of this agent is C and ft is not preferred during pregnancy and lactation. The aids effects may he expected * such as irritation, redness, etc. Me skin nourishing and moistening property is present. Use during the daytime is not recommended, or limited. Topical antibiotic-containing agents (erythromycin, clindamycin, etc.): These agents are effective against bacteria but unfortunately they encounter resistance today, in ether words, bacteria grow and cause acne lesions despite the use of antibiotics.
  • Topical retinoic acid and retinoids are frequently preferred ccmedolyhc agents in mild to moderate acne. However, they cannot be used during the daytime, they are not recommended for use during pregnancy and breastfeeding, sad may often cause side affects eyed as irritation, redness, and burning. Patients should be careful about the amount used end the time of use, in short, these are the agents which are difficult to use and adapt and act within minimum few months, not in a few days. No skin nourishing effect is present,
  • Aseiaic acid It is one of the topical agents used In the acne fraatment. This agent may also cause redness, irritation, burning when used In excessive amounts or applied to the patients with a sensitive skin, its effect is oof expected to occur within days, and there Is no information that it nourishes and moisturises the skin.
  • compositions containing alpha hydroxy acids, beta hydroxy acids, glycolic acid, lectio acid, etc. These an frequently used in the acne treatment as a comsdoiytie. However, they often cause side effects such as redness, burning, stinging and Irritation on the skin.
  • the invention relates to an anti-acne and antibacterial lotion which may be formed by using niacinamide together with sodium chloride of specified ratios and/er pantothenic acid of specified ratios, may be applied easily onto acne, may act within a short period of time such as within few days, and may treat the aones without causing drying of skin.
  • chloride used in this formula if has also been shown to perform microdermabrasion for acne, that is, have both a slight exfo!ant property on the fop layer of the skin, and an effect which absorbs the oil, meaning sehum, in the skin (references 2, 3),
  • Niacinamide which Is one of the ingredients of the lotion according to the Invention, is actually a form of vitamin 8. Niacinamide has been used In several studies that have been effective for aone since 1995, especially by comparing Its efficacy with clindamycin, a topical antibiotic, and Its successful results have been reported, in these publications, gel formulations of 2% and 4% were used (reference 9). Combinations with niacinamide were formed with clindamycin to date and, in a study, with tretinoin (a retinoic acid derivative) and 7-dehydrochoiesferoi of 0.5%.
  • niacinamide was used to balance the akin microbiola, a protection was intended against the attack of microorganisms on tbs skin or scalp, and the benign normal flora elements was supported white the microbes attacking from the outside were Intended to be reduced, in addition, niacinamide has been used for the treatment of bad odors on the skin.
  • niacinamide or its precursors am used in the range of 0,1-8%, and this ratio of niacinamide is dissolved in a base. While other optional ingredients may be added to this composition, It is not necessary, snd skin bleaching agents or ultraviolet protectors is often used.
  • niacinamide is applied against harmful microbial elements, wherein niacinamide is used in a lotion form, in a water-containing formulation and with a combination of sodium chloride of more than 5%, usually close to 10% ⁇ in a range of 7-10%) and above 2%, and pantothenic acid of 0,5% and above.
  • the formulation does not overlap and does not use our combination,
  • the patent US200801424? A (lu at at,, 2008) on the same subject is a formulation developed to treat various bacteria and fungi and contains stearic acid and a metal that may be silver, thus I is not similar to our combination.
  • Said pantothenic add in the formulation of our invention is not actually an acid but a B-group vitamin (vitamin 85).
  • a B-group vitamin vitamin 85
  • the patent US3Q50467 81 Horowitz et ai. 1962
  • an antimiorobiai formula baa been developed with a synergistic effect of a silver-containing sal and a soap.
  • the formulation of our invention Is a combination of 2 organic vitamins (niacinamide and pantothenic acid) and sodium chloride which is found both in body fluids and table salt.
  • niacinamide for inducing generation of antimicrobial peptides
  • niacinamide has been used to create antimicrobial peptides, wherein niacinamide is applied to the skin surface, scalp or mouth as a prophylactic, and I is aimed to prevent microbes that may come end stick to these areas in the future.
  • niacinamide has been used In a microbiome- balancing formula, however the dose of niacinamide was In the range of G,1% ⁇ 5%, preferably in the range of 1-3%, as in WO201688832?» However, it is not mentioned to increase the antimicrobial activity of the niacinamide levels of 5% and above in our formula by combining hyperosmolar sodium chloride of 2% and above and pantothenic acid of 0.5% and above. Many exemplary formulas are given, but hyperosmolar sodium chloride are hot combined at doses of 2% and above in none of them.
  • niacinamide for inducing generation of antimicrobial peptides is similar to WO2015172801 and WO2019086327. wherein niacinamide is used alone and is added at a concentration of 0.1-5% due to its antimicrobial effect In various cosmetic: formulations. However, the potentiation of the antimiorobiai efficacy with hyperosmolar sodium chloride of 2-8% or pantothenic aoid of 0,8% and above, l ⁇ ., an increase in the efficacy is not mentioned.
  • niacinamide is applied against harmful microbial elements, wherein niacinamide is used in a lotion form, in a water-containing s fornication and with a combination of sodium chloride of more than 5%, usually close to 10% (in a rang ⁇ ⁇ f 7-10%) and above 2%. preferably 3% and above and pantothenic acid of 0.5% and above.
  • the formulation does not overlap and does not use our combination.
  • VVO2018004212 in the patent titled “antioxidant composition for skin 8 , for an antioxidant effect, niacinamide is combined with fermented yeast and an alpha ketogiotarie acid and is intended for use as a cosmetic or pharmaceutics! product. Both products are not present in the formula of our invention, end the purpose of our formulation differs.
  • WO2017210238 In the patent titled “aoti-aone compositions and methods of use * , niacinamide is combined with sulfur and phenylethy! resorcinol. While glycolic acid and allantoic may also be added to this formula, our formula and scope are completely different.
  • niacinamide may also be used alone at ratios of 2J ⁇ 5%.
  • pantothenic acid may be added in addition to niacinamide.
  • sodium chloride is not present in this mixture.
  • the amounts of niacinamide and/or pantothenic acid have not been determined on the basis of doses that will produce antibacterial effects The object of the patent is not to provide an
  • steroids as a drug and/or active ingredients of the anti-inflammatory drugs as well as antibiotics such as tetracycline, clindamycin, etc. may be added
  • antibiotics such as tetracycline, clindamycin, etc.
  • vitamin B3 s niacinamide
  • pyridoxins vitamin 88
  • the object of our invention is to form an antibacterial organic compound in which no drugs and antibiotics ere present and thus, no resistance wti! develop fbereagainsi in ether words, drug use is never considered by us.
  • EP273419S and US20150050342 and WO/2013/01442? fitted “compositions for treatment of skin disorders” are the same patents and consist of a combination of antiseptic ohforhexidine or a sat thereof with salicylic add or a sail thereof and niacinamide, as a treatment agent in bacteria? skin diseases and acne.
  • pantothenic odd in the formula of cur invention is actually vitamin 85 and is added to the formulation due to the effect of the adds on the bacteria, not their exfoliating properties.
  • Salicylic acid Is a strong exfoliating add and is not related to the vitamins.
  • eucalyptol and chlorhexidine are added as an antibacterial, and also sine pyrogiutamate, tocopherol as an antioxidant, and yellow chamomile essential oil may be present in the formulation.
  • the ratio of niacinamide is in the range of 0.2 and 535
  • niacinamide ⁇ related skin treatments are intended mostly for cosmetic purposes, for example for bleaching the skin, treeing skin spots, alleviating rosacea or skin wrinkle, eliminating the dryness of skin, regenerating the skin.
  • the compositions thereof do not contain sodium chloride at a concentration of 2% and above.
  • the object is to use a mixture of 3 organic;, non-irritating, drug- and antibiotic-free and cost effective substances, the antibacterial efficacies of which are individually demonstrated, as a first line treatment and prophylactic for the skin disorders with a bacterial mechanism, such as tor example, acne, folliculitis, impetigo, ate.
  • Therapeutic and prophylactic doses may vary. This combination aims at both increasing the effectiveness of each substance and reducing the likelihood of resistance development.
  • resistance of bacteria to the antibiotic-containing drugs is an important problem.
  • the combination of more than one substance with an antibacterial activity in a composition that is not antibiotic end drug-free is valuable.
  • sodium chloride is used instead of any salt at doses of 2% and above, preferably In the range of 3-6%, This is because the antibacterial efficacy of sodium chloride at these doses has been demonstrated, as shown In the references (references 2,3.4.5,8,7, 8,3, 10, 11 ,12),
  • niacinamide in the range of 6-10% and sodium chloride In the range of 3-8% are mixed in warm water.
  • This formulation Is directly applied onto a folliculitis or acne lesion.
  • pantothenic acid in the range of 0,5-8% is mixed in warm water in addition to niacinamide In the range of 5-10% and sodium chloride In the range of 2-8%. This formulation may be applied onto the entire surface.
  • Preparing the lotion of the invention by dissolving it in warm water provides, shove ail, ease of application and cost effectiveness, it also makes i possible to apply the niacinamide product used directly to the skin of an Individual at a desired percentage without any change.
  • the main object of the Invention is that the lotion Is rapkParding as well as economical and practical.
  • the lotion of the invention which is prepared by dissolving in warm water, provides for the niacinamide and pantothenic acid therein to he applied without any change and in a pure and direct manner without mixing with any stabilizer or preservative. This atso provides ease of use In pregnant women and children.
  • the lotion which is completely natural dee to its vitamin and sodium chloride sail content, may he easily absorbed from the skin owing to the hydrophilic characteristic thereof
  • the lotion of the present invention has a new concept among the formulations used in the treatment of acne in that there is no any other fommletion directly containing vitamins and that the formulation is hydrophilic, is not in the form of a gel or cream, and Is free of any stabilizer or preservative and a drug, in the formulation of the invention, pantothenic acid and/or a derivative thereof ⁇ Ca ⁇ D pantothenate) in the range of 0.5*6% is present
  • niacinamide namely vitamin 13, and/or a derivative thereof in the range of 5-10%, preferably more than 5%
  • sodium chloride in the range of 2-8% and may be applied onto the entire face.
  • the pantothenio acid herein is vitamin 0S. It is completely natural owing to vitamin (B8 and 85) and sodium chloride fan organic salt) content thereof.
  • Pantothenic acid and/or derivatives thereof do net intend to exfoliate and dry the skin as an acid, they am included in the formula to both give moisture to the skin as a vitamin derivative and suppress the bacteria f reference 10),
  • the formulation of the invention actually has a dual activity of antibacterial and mechanical
  • the combination of sodium chloride, pantothenic acid and/or a derivative thereof and niacinamide in the formula show antibacterial activities; and sodium chloride and niacinamide both mechanically reduce the oil oh the skin surface, while pantothenic acid and/ or a derivative thereof prevents excessive drying and eliminates irritation by providing moisture.
  • the salt in the formula is mt any salt, but sodium chloride, which is found in the body as serum. No any other sal is used.
  • Sodium chloride Is an essential, easy ⁇ lo ⁇ fi nd, cost- efficient and effective antibacterial agent that b m ' own to prevent biofim formation for some bacteria, absorbs sebum, and may also provide micfodermabraefoa This agent may regress swelling, prominence, edema of the lesions in a short time after application as it is at a hyperosmolar concentration of over 0 J percent,
  • pantothenic add and/or a derivative thereof in the formula also contribute to antibacterial activity, including staphylococci ⁇ reference 10).
  • the formulation Is a drug-free functional formula having mechanical properties without any immunological or enzymatic mechanisms; hyperosmolar sodium chloride solution dehydrates and destruets mechanically bacteria and other microbes according to osmoiarity principles and performs a mechanical cleansing by providing microdemiabrasion on the skin surface ⁇ reference 10); niacinamide absorbs the excessive sebum (oil in the skin); and pantothenic acid or a derivative thereof (not an add, but vitamin 85) moisture the skin,
  • Example 1 in the case that the formulation which was applied onto a volunteer subject who was iollowed-up using pictures was applied cnee a day for IS minutes and washed, the lesions were determined to he smaller as from the third day. The effect was determined to he continued Increasingly In the following days. No Irritation developed during the application of the formulation consisting of two vitamin derivatives end a sail
  • Microdemmbmsioo An Evidence Based Review, Plastic and Reconstructive Surgery 120(1) 872-377, Kanmipour CM, Kersmlpcur G submit Grringar JS,

Abstract

The Invention relates to a solution formed by using niacinamide together with sodium chloride of specified ratios and/or pantothenic add of specified ratios, which solution is easily applicable on acne, acts in a short period of time such as few days and does not. lead to drying of skin during the treatment of the bacterial skin lesions and active acne lesions. The invention also relates to a lotion, against which s resistance is not developed, which does not contain a drag and an antibiotic and thus is available oven the-counter, wherein said lotion Is used safely in pregnant women and children of all ages for the prevention or treatment of lesions that develop with the effect or contribution of bacteria on the skin surface, such as acne, folliculitis, etc,

Description

A DRUOFREE ARTIBACTERf AL LOTIOM
The invention relates to a drug -free lotion, against which a resistance Is not developed, for the freetment of the bacterial skin lessons and active acne lesions without causing skin dehydration, which may he used for everyone including pregnant women and children of ell ages and may he formed by using niacinamide together with sodium chloride of specified ratios and/or pantothenic acid of specified ratios, wherein the drug- free lotion of the invention may be applied easily on the oily skin end acts in a short period of time such as few days upon contact for 10-15 minutes par day, The invention is a lotion, against which a resistance is not developed, which does not contain a drug and/or an antibiotic and thus is available overdhmcounter, wherein said lotion may be used safely in pregnant woman and children of all ages for the prevention or treatment of lesions that develop with the effect or contribution of bacteria on the skin surface, such as acne, folliculitis, etc,
Antibiotic end antiseptic resistance is an Increasing problem during recent years (Reference 1). Accordingly, formulations that are net antibiotics, antiseptic and drugs but have an antibacterial efficacy will continue to remain on the agenda. Said invention relates to a public access, first-line antibacterial formulation, an efficacy on the bacteria of which has been demonstrated, which formulation Is cost-effective, easy to prepare and cheap, wherein said formulation is not a drug, thus, a resistance against its mechanical impact Is difficult to develop, wherein said efficacy does not contain an enzymatic step, an immunological reaction, etc,
Use of formulations is restricted due to the active ingredients and the like, which has an antibacterial efficacy but Is difficult and laborious to reach, or is expensive, rare and found In some parts of the world. Therefore, organic, easy-to-find, cost-effective materials that will not force people financially are used in the formulation of the invention.
For example: an antibacterial formulation is presented in the patent document CN108522S47 titled ’'anti bacterial care solution composition and application thereof, but the formulation contains an extract of “taxes ehinensis (Chinese yew}’*, in our formula, local and hsrd-to-find substances are not used. ί The substances selected for our formulation are organic substances that have no drug affects and are easily available, and era created by the combination of effective and safe concentrations. Each of them Is organic antibacterial non- drug substances. The most important reason for forming a composition is to prevent the development of antibacterial resistance and to strengthen the effect (references
1 ,2,3,4.5,8, 7,8,9, 10, 11,12). In this way, a combination has been obtained, which both reduces the number of bacteria and concurrently performs microdermahrasion (skin exfoliation): wherein the combination reduces the bacteria using the mechanical and 'osmotic shock" protocols on the akin surface, while preventing the resistance development and reducing the sebum without causing skin dehydration. This combination may be diversified, but the three basic components are unchangeable and required for their tasks. However, concentrations may vary when used for treatment or prophylaxis Acne is a common condition that may be seen in teens and during puberty and is difficult to treat. A pronounced oily skin accompanied by bacterial causes Is among the reasons. Therefore, the effect of bacterial growth in an oily secretion background secreted in the skin, called sebum, is important. At this point, the method or agents that reduce the oil in the skin and the methods or substances that reduce the number of bacteria gain importance in the treatment of acne. However, acne treatment is difficult for the following reasons.
The patient usually has oily skin, and the agents used to remove this oil may cause excessive drying of skin, in addition, if is known that a large variety and number of microorganisms are produced In an oily secretion medium, called sebum, which facilitates the growth of seme bacteria on this oily skin surface, Especially, Cutibactehum acoes has a particular important place among the causes of acne. The treatment agents (such as combinations containing different acids, alcohol· soluble formulae) given for drying the lesions quickly may causa Irritation, redness and burning on the skin. The treatment agents that do not cause Irritation and redness on the skin have limited success in drying up the lesions or preventing the lesions from developing.
Today, a wide variety of lotions , creams and gels ere available on the market for the acne treatment, but their side effects limit their use. Treatment success for acne is generaliy low. A wide variety of side effects have been reported about systemic agents, namely pis, available on the market, and patients or their families are Increasingly reluctant to use these agents, in addition, patients who are at the age of becoming pregnant, pregnant or breastfeeding are completely excluded from the acne treatment. This leads to physiologically and psychologically negative outcomes on the person.
An ideal agent for the none treatment should provide a alight exfoliation while mosstening the skin to ensure the exfoliation net to be seen and also should rapidly dry the developing lesions before growing without causing any irritation, redness, burning, it should also nourish the skin and prevent it from getting thinner, in addition, they should be able to ba used easily by the patients at child bearing age, or pregnant patients or breastfeeding patients. It should not be a drug, ft should be used safely and comfortably at any age, and It should also be cost effective, i.e. not he expensive and not contain substances that are difficult to find
Petals about externally applied (topical) agents for the acne treatment and uses
Benzoyl peroxide: This Is on agent which may be used frequently, have side effects such as redness, burning and irritation on the akin, be considered as a drug and have no skin nourishing end moistening property,
Salicylic· acid: This is an agent which may be considered as a drug and is Intended to be used for exfoliating the skin and drying the lesions. It is comedoiytic and one of the most used agents for the acne treatment. The pregnancy category of this agent is C and ft is not preferred during pregnancy and lactation. The aids effects may he expected* such as irritation, redness, etc. Me skin nourishing and moistening property is present. Use during the daytime is not recommended, or limited. Topical antibiotic-containing agents (erythromycin, clindamycin, etc.): These agents are effective against bacteria but unfortunately they encounter resistance today, in ether words, bacteria grow and cause acne lesions despite the use of antibiotics.
Topical retinoic acid and retinoids: Retinoic acid and derivatives thereof are frequently preferred ccmedolyhc agents in mild to moderate acne. However, they cannot be used during the daytime, they are not recommended for use during pregnancy and breastfeeding, sad may often cause side affects eyed as irritation, redness, and burning. Patients should be careful about the amount used end the time of use, in short, these are the agents which are difficult to use and adapt and act within minimum few months, not in a few days. No skin nourishing effect is present,
Aseiaic acid; It is one of the topical agents used In the acne fraatment. This agent may also cause redness, irritation, burning when used In excessive amounts or applied to the patients with a sensitive skin, its effect is oof expected to occur within days, and there Is no information that it nourishes and moisturises the skin.
Compositions containing alpha hydroxy acids, beta hydroxy acids, glycolic acid, lectio acid, etc.: These an frequently used in the acne treatment as a comsdoiytie. However, they often cause side effects such as redness, burning, stinging and Irritation on the skin.
The invention relates to an anti-acne and antibacterial lotion which may be formed by using niacinamide together with sodium chloride of specified ratios and/er pantothenic acid of specified ratios, may be applied easily onto acne, may act within a short period of time such as within few days, and may treat the aones without causing drying of skin.
In addition to the antibacterial effects of sodium: chloride used in this formula, if has also been shown to perform microdermabrasion for acne, that is, have both a slight exfo!!ant property on the fop layer of the skin, and an effect which absorbs the oil, meaning sehum, in the skin (references 2, 3),
Niacinamide, which Is one of the ingredients of the lotion according to the Invention, is actually a form of vitamin 8. Niacinamide has been used In several studies that have been effective for aone since 1995, especially by comparing Its efficacy with clindamycin, a topical antibiotic, and Its successful results have been reported, in these publications, gel formulations of 2% and 4% were used (reference 9). Combinations with niacinamide were formed with clindamycin to date and, in a study, with tretinoin (a retinoic acid derivative) and 7-dehydrochoiesferoi of 0.5%. In these studies using niacinamide, cream and gei formulations were used, end it has not been applied as a hydrophilic solution in wa ter. In addition, the combination of sodium chloride and pantothenic add has not been found in these previous studies, in 2010, an exudate form developed with the “Niacinamide in hot melt extrusion" method was developed, a publication of this was determined, but it was understood that there was no formulation developed by direct dissolution in warm water. invention:
W02C* 1908832? ···· In the patent titled "use of niacinamide for microdome balancing*, niacinamide was used to balance the akin microbiola, a protection was intended against the attack of microorganisms on tbs skin or scalp, and the benign normal flora elements was supported white the microbes attacking from the outside were Intended to be reduced, in addition, niacinamide has been used for the treatment of bad odors on the skin. To this end, niacinamide or its precursors am used in the range of 0,1-8%, and this ratio of niacinamide is dissolved in a base. While other optional ingredients may be added to this composition, It is not necessary, snd skin bleaching agents or ultraviolet protectors is often used.
However, the anti-microbial efficacy is not mentioned or to be potentiated with hyperosmolar sodium chloride of 2-3% and above, or pantothenic acid in doses of 0,5% and above, as in our invention. in the formulation of our invention, niacinamide is applied against harmful microbial elements, wherein niacinamide is used in a lotion form, in a water-containing formulation and with a combination of sodium chloride of more than 5%, usually close to 10% {in a range of 7-10%) and above 2%, and pantothenic acid of 0,5% and above. The formulation does not overlap and does not use our combination,
Also, the patent US200801424? A (lu at at,, 2008) on the same subject is a formulation developed to treat various bacteria and fungi and contains stearic acid and a metal that may be silver, thus I is not similar to our combination. Said pantothenic add in the formulation of our invention is not actually an acid but a B-group vitamin (vitamin 85). We do not use metal or stearic acid. in the patent US3Q50467 81 (Horowitz et ai. 1962), an antimiorobiai formula baa been developed with a synergistic effect of a silver-containing sal and a soap. The formulation of our invention Is a combination of 2 organic vitamins (niacinamide and pantothenic acid) and sodium chloride which is found both in body fluids and table salt.
WO2015179570 - In the patent titled “waterborne topical compositions for the deliver/ of azeia!c acid for treatment of skin conditions ouch as acne vulgaris, rosacea seborrheic dermatitis*, the absorption of ase!alc add from the akin surface Is aimed to be increased, wherein niacinamide is combined with aze!aie add. No add/ azeiaic add is present In our invention. Said pantothenic add Is a form df vitamin B (vitamin 85).
VV02D1 si 72801 ~ In the patent titled “niacinamide for inducing generation of antimicrobial peptides”, niacinamide has been used to create antimicrobial peptides, wherein niacinamide is applied to the skin surface, scalp or mouth as a prophylactic, and I is aimed to prevent microbes that may come end stick to these areas in the future. for another formula, the same percentages and the same expressions were used in W02C>1 <5086327 and CN 106413680 and 102817/0868? (all of three may be the same patent) as WO201908832?, wherein niacinamide has been used In a microbiome- balancing formula, however the dose of niacinamide was In the range of G,1%~5%, preferably in the range of 1-3%, as in WO201688832?» However, it is not mentioned to increase the antimicrobial activity of the niacinamide levels of 5% and above in our formula by combining hyperosmolar sodium chloride of 2% and above and pantothenic acid of 0.5% and above. Many exemplary formulas are given, but hyperosmolar sodium chloride are hot combined at doses of 2% and above in none of them.
882742842 - The patent titled “niacinamide for inducing generation of antimicrobial peptides” is similar to WO2015172801 and WO2019086327. wherein niacinamide is used alone and is added at a concentration of 0.1-5% due to its antimicrobial effect In various cosmetic: formulations. However, the potentiation of the antimiorobiai efficacy with hyperosmolar sodium chloride of 2-8% or pantothenic aoid of 0,8% and above, l©., an increase in the efficacy is not mentioned. In the formulation of our Invention, niacinamide is applied against harmful microbial elements, wherein niacinamide is used in a lotion form, in a water-containing s fornication and with a combination of sodium chloride of more than 5%, usually close to 10% (in a rang© ©f 7-10%) and above 2%. preferably 3% and above and pantothenic acid of 0.5% and above. The formulation does not overlap and does not use our combination.
US2004D081672 ··- In the patent titled “niacinamide, niacin, and niacin esters based delivery systems for treating topical disorders of skin and skin aging*, a formula has been formed for use in disorders such as rosacea, skin aging, and spots on skin by combining niacinamide with organic acids such as alpha hydroxy acids or glycolic acid. it has been reported that niacinamide may be combined with salicylic acid derivatives for acne in the same formulation. This is quite different from the combination and scope of our invention.
VVO2018004212 - in the patent titled “antioxidant composition for skin8, for an antioxidant effect, niacinamide is combined with fermented yeast and an alpha ketogiotarie acid and is intended for use as a cosmetic or pharmaceutics! product. Both products are not present in the formula of our invention, end the purpose of our formulation differs. WO2017210238 - In the patent titled “aoti-aone compositions and methods of use*, niacinamide is combined with sulfur and phenylethy! resorcinol. While glycolic acid and allantoic may also be added to this formula, our formula and scope are completely different. ffiaofnamide and pantothenic acid is used together in the formula of EP0856688 md WO1997017O60 entitled “topical compositions for regulating the oily /shiny appearance of skin*, wherein this patent Is reported to be produced to prevent oily appearance of the skin. This patent is different from our patent In that no sodium chloride is present, no antibactenai efficacy is mentioned, and the object is only to provide a radiant skin and to prevent an oily skin,
As it is understood from this patent, niacinamide may also be used alone at ratios of 2J~5%. Furthermore,: pantothenic acid may be added in addition to niacinamide. However, sodium chloride is not present in this mixture. In addition, the amounts of niacinamide and/or pantothenic acid have not been determined on the basis of doses that will produce antibacterial effects The object of the patent is not to provide an
1 antibacterial efficacy against which a resistance nn·ϋ cat develop without any drug and antibiotic:, but to avoid the oily appearance on a face.
In addition, steroids as a drug and/or active ingredients of the anti-inflammatory drugs as well as antibiotics such as tetracycline, clindamycin, etc. may be added In addition to the vitamin constituents ia,s niacinamide (vitamin B3) end pantothenic acid (Vitamin 8o>, pyridoxins (vitamin 88).
The object of our invention is to form an antibacterial organic compound in which no drugs and antibiotics ere present and thus, no resistance wti! develop fbereagainsi in ether words, drug use is never considered by us.
EP273419S and US20150050342 and WO/2013/01442? fitted “compositions for treatment of skin disorders” are the same patents and consist of a combination of antiseptic ohforhexidine or a sat thereof with salicylic add or a sail thereof and niacinamide, as a treatment agent in bacteria? skin diseases and acne.
The important point is that the pantothenic odd in the formula of cur invention is actually vitamin 85 and is added to the formulation due to the effect of the adds on the bacteria, not their exfoliating properties. Salicylic acid Is a strong exfoliating add and is not related to the vitamins.
Here, eucalyptol and chlorhexidine are added as an antibacterial, and also sine pyrogiutamate, tocopherol as an antioxidant, and yellow chamomile essential oil may be present in the formulation. The ratio of niacinamide is in the range of 0.2 and 535
In addition, in this patent, while it is aimed to produce an acidic product, both the content and pH is not related to our water-soluble'- non-acidie. natural and uncomplicated practical formulation. In fact, it is known that the formulas with acidic pH have side effects such as irritation, redness end pain in the treatment of acne. The formulation of our invention Is not preferred to have such undesired side effects.
As seen In these examples, the patents for niacinamide · related skin treatments are intended mostly for cosmetic purposes, for example for bleaching the skin, treeing skin spots, alleviating rosacea or skin wrinkle, eliminating the dryness of skin, regenerating the skin. The compositions thereof do not contain sodium chloride at a concentration of 2% and above.
In our invention, the object is to use a mixture of 3 organic;, non-irritating, drug- and antibiotic-free and cost effective substances, the antibacterial efficacies of which are individually demonstrated, as a first line treatment and prophylactic for the skin disorders with a bacterial mechanism, such as tor example, acne, folliculitis, impetigo, ate. Therapeutic and prophylactic doses may vary. This combination aims at both increasing the effectiveness of each substance and reducing the likelihood of resistance development. Nowadays, resistance of bacteria to the antibiotic-containing drugs is an important problem. Thus, the combination of more than one substance with an antibacterial activity in a composition that is not antibiotic end drug-free is valuable. in addition, in the formula of our Invention, sodium chloride is used instead of any salt at doses of 2% and above, preferably In the range of 3-6%, This is because the antibacterial efficacy of sodium chloride at these doses has been demonstrated, as shown In the references (references 2,3.4.5,8,7, 8,3, 10, 11 ,12),
In the first formulation, niacinamide in the range of 6-10% and sodium chloride In the range of 3-8% are mixed in warm water. This formulation Is directly applied onto a folliculitis or acne lesion. In the second formulation, pantothenic acid in the range of 0,5-8% is mixed in warm water in addition to niacinamide In the range of 5-10% and sodium chloride In the range of 2-8%. This formulation may be applied onto the entire surface.
Drying the lesions quickly Is intended with these two agents in the first formulation. This formula has been developed to be applied on active acne lesions. Occasionally, side effects of niacinamide such as redness, burning and irritation Nava bean determined wherr used alone, or in combination with o!ndamycin, or in combination with irefln and T-dehydrocholesterp!, Thus, in our second formulation developed to be applied on tbe entire face, pantothenic acid is present at doses in the range of tt.5-5% and aims to moisturiae the skin againsf possible dryness and eolation. Preparing the lotion of the invention by dissolving it in warm water provides, shove ail, ease of application and cost effectiveness, it also makes i possible to apply the niacinamide product used directly to the skin of an Individual at a desired percentage without any change. The main object of the Invention is that the lotion Is rapkParding as well as economical and practical.
The lotion of the invention, which is prepared by dissolving in warm water, provides for the niacinamide and pantothenic acid therein to he applied without any change and in a pure and direct manner without mixing with any stabilizer or preservative. This atso provides ease of use In pregnant women and children. The lotion, which is completely natural dee to its vitamin and sodium chloride sail content, may he easily absorbed from the skin owing to the hydrophilic characteristic thereof
The lotion of the present invention has a new concept among the formulations used in the treatment of acne in that there is no any other fommletion directly containing vitamins and that the formulation is hydrophilic, is not in the form of a gel or cream, and Is free of any stabilizer or preservative and a drug, in the formulation of the invention, pantothenic acid and/or a derivative thereof {Ca~D pantothenate) in the range of 0.5*6% is present In addition to niacinamide, namely vitamin 13, and/or a derivative thereof in the range of 5-10%, preferably more than 5%, and sodium chloride in the range of 2-8% and may be applied onto the entire face. The pantothenio acid herein is vitamin 0S. It is completely natural owing to vitamin (B8 and 85) and sodium chloride fan organic salt) content thereof.
Pantothenic acid and/or derivatives thereof do net intend to exfoliate and dry the skin as an acid, they am included in the formula to both give moisture to the skin as a vitamin derivative and suppress the bacteria f reference 10), In addition, the formulation of the invention actually has a dual activity of antibacterial and mechanical
The combination of sodium chloride, pantothenic acid and/or a derivative thereof and niacinamide in the formula show antibacterial activities; and sodium chloride and niacinamide both mechanically reduce the oil oh the skin surface, while pantothenic acid and/ or a derivative thereof prevents excessive drying and eliminates irritation by providing moisture.
The salt in the formula is mt any salt, but sodium chloride, which is found in the body as serum. No any other sal is used. Sodium chloride Is an essential, easy~lo~fi nd, cost- efficient and effective antibacterial agent that b m ' own to prevent biofim formation for some bacteria, absorbs sebum, and may also provide micfodermabraefoa This agent may regress swelling, prominence, edema of the lesions in a short time after application as it is at a hyperosmolar concentration of over 0 J percent,
3~8% of sodium chloride, which creates an osmotic shock in the environment due te the hyperosmolar solution property of the substances In the mixture, has the ability to change the number of bacteria and the environment per se (reference 8). Although Its ant!hseier!sf effect is limited especially for ‘Staphylococcus Aureus”,, which is an important bacterium on the skin, it helps to Increase the antibaeterfa! properties of the components other than Itself, niacinamide and pantothenic acid, to decrease the possibility of a resistance development, end to prevent gram negative bacteria that may be added te the clinical piolure by creating a hyperosmolar shook environment (references 2»3AS,§,T>§ J, 10,11,12). On the other hand, the pantothenic add and/or a derivative thereof in the formula also contribute to antibacterial activity, including staphylococci { reference 10).
The formulation Is a drug-free functional formula having mechanical properties without any immunological or enzymatic mechanisms; hyperosmolar sodium chloride solution dehydrates and destruets mechanically bacteria and other microbes according to osmoiarity principles and performs a mechanical cleansing by providing microdemiabrasion on the skin surface {reference 10); niacinamide absorbs the excessive sebum (oil in the skin); and pantothenic acid or a derivative thereof (not an add, but vitamin 85) moisture the skin,
Therefore, the formulations, proportions and percentages are adjusted at a precision enough to perform many functions. Both the antibacterial activities and mechanical activities of these three substances were taken into consideration. In addition, another object of the present Invention is to be used easily for children of ail ages and pregnant women, so a drug-free formulation is essential. Examples of some applications of the invention:
Example 1, in the case that the formulation which was applied onto a volunteer subject who was iollowed-up using pictures was applied cnee a day for IS minutes and washed, the lesions were determined to he smaller as from the third day. The effect was determined to he continued Increasingly In the following days. No Irritation developed during the application of the formulation consisting of two vitamin derivatives end a sail
Example 2 «
After the application to the voluntary subject with a papule and pustule lesions of the acne once a day, a significant regression was observed in the acne lesions as from the third day, and no effect such as irritation, etc. was detected,
Example 3,
Eatma GOiru Erdoifon let! the formulation on the lesion for five minutes for the only folliculitis on her lip, and at the end of this period, she found that the lesion regressed and the pain relieved significantly. One day after the single application, the lesion became smaller and disappeared. No any ondesirad effect was developed, such as Irritation. Table 1 « A scheme for the field of use for the formulation
Figure imgf000013_0001
*Seeondary Infection indicates the presence of an extra bacterial Infection upon conditions that are not depending on the bacterial causes. References;
1. Mechanisms of increased Resistance to Chiorhexidine and Cress-Resistance to Coistin following Exposure of KfePsfefe pnmfmnm® Clascal Isolates to Cbiorhexidiee, Matthew E. Wandj lacy d. Bock, Laura C Bonney, and J. Mark Suttonu Antlmicrob Agents Chenioiher, 2017 Jan; 81(1): eO1182-18.
2, Lloyd OR. The use of rntorcvJermabrasion for acne; A plot study, Dermatol Surg. 2001 :27:329~331
3. Microdemmbmsioo : An Evidence Based Review, Plastic and Reconstructive Surgery 120(1) 872-377, Kanmipour CM, Kersmlpcur G„ Grringar JS,
4, Feed Microbiol. 2006 Oct.;23(?):85?-82. Epub 2006 Jan 10, Antimicrobial properties of sai (NaC!) used for the preservation of natural casings, Wfnker Jdf, Koop G, Upman LJ,
8 Journal of Hospital infection, Compressedsodum chloride as a fast acting antimicrobial surface; a pilot study Volume 94, 2018.
8, Advances toward the Elucidation of Hypertonic Saline Effects on P s e u d o m o n a s e e r u g 1 n o s a from Cystic Fibrosis Patients. Anne~taure Miehon1:2\ Estelle dumas-BiiakL3s Raphae 1 Ohiron4, Brigitte Lamy, Plosone 2014; volume 9.
7, TOLERANCE OF STAPHYLOCOCCUS AUREUS TO SODIUM CHLORIDE I, A. BARPENTJEY. ANNA R, CATELLI institute of Applied Biology. New York* New York, Journa of Bacteriology Volume 88,
8, Characterization of Cofynebacfenum acaes :
By S. MADLI FUHVEt Department of Medicine* Division of Dermatology, University of California* School of Medicine. Los Angeles, California 30024. U.S.A. Volume 30, 8v The effect of 2% niacinamide on facial sebum production
Zoo Diana Draelos, Akira Mafsubara A Kenneth Smiles, Journal of Cosmetic and Laser Therapy* 2009; 3: 96-101
19. Anfimierobial Activity of Panfothenol against .Staphylococci Possessing a Prokaryot-c Type II Pantothenate Kinase Shigeru Chohnari1,2s * MiSe MuraSet, Kota KuriKawal Kodai higaShil* and Yota Ogata, Microbes Environ, Voi, 29, No, 2. 224- 228* 2014.
11, Use of eaioein and SYT043 to assess ceii eyo!e phases and osmotic shock effects on E, coil and Staphylococcus aureus by tow cytometry, , Jaume Comas-Rtu , Josep Vlves-Rego. Journal of Microbiological Methods 34 (1999) 218-221 12.. Skin Barrier Changes induced by Aluminum Oxide and Sodium Chloride Microdermadrasson. Poonani Rajan 1 , Pearl E Crimes. Dermatol Surg 2002 May;28(5);380-3.

Claims

I An acne lotion obtained by dissolving niacinamide (vitamin 83), sodium chloride and pantothenic acid and/or a derivative (vitamin 85) in warm water for use in the prevention and treatment of lesions that develop under the influence of bacteria on the skin surface, such as acne, folliculitis, etc., characterized In that it has two different formulation comprising:
- niacinamide to the range of 6-10% and sodium chloride in the range of 3-
8%,
~ niacinamide in trie range of 540%, sodium chloride in the range of 3-3% and pantothenic acid and/or a derivative In the range of 0.6-6%,
2. An antlbacteriai/acne lotion according to claim 1 characterized by a skin moistening: property during use.
An antibaeierial/scne lotion according to claim 1, characterized in that It is applied only on the acne or over the entire face. 4. An anfibacterial/acne lotion according to claim 1, characterized in that I does not comprise a drug.
S. An antlbacteriai/acne lotion according to claim 1, characterized in that it may bo need in pregnant women and children.
8. An antlbacteriai/acne lotion according to claim 1, characterized in that niacinamide and pantothenic acid in the lotion may be applied without any change and in a pure end direct manner without mixing with any stabilizer or preservative.
7. An an!bacteriat/aone lotion according to claim 1 * characterized in that it may be easily absorbable from the skin owing to its hydrophilic property.
An antihacfersat/sooe lotion according to claim 1, characterised in that sodium chloride used in the formulation is a sail which Is used as serum In the body.
0. An aniibacierial/acne lotion according to claim 1, characterised In that it has a dual activity of both antibacterial and mechanical.
PCT/TR2020/000008 2020-06-08 2020-06-08 A drug-free antibacterial lotion WO2021257009A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001000162A1 (en) * 1999-06-28 2001-01-04 The Procter & Gamble Company Cosmetic compositions containing vitamin b3
DE102009052808A1 (en) * 2009-11-13 2011-05-26 Roman Hasenkopf Ointment, useful e.g. for treating salt deficiency, acute and chronic trauma, comprises ointment base and homeopathically diluted mineral salt including e.g. calcium phosphate, iron phosphate, potassium chloride and potassium phosphate
US20180243332A1 (en) * 2010-07-22 2018-08-30 Reven Pharmaceuticals, Inc. Method of treating or ameliorating skin conditions with a magnetic dipole stabilized solution

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001000162A1 (en) * 1999-06-28 2001-01-04 The Procter & Gamble Company Cosmetic compositions containing vitamin b3
DE102009052808A1 (en) * 2009-11-13 2011-05-26 Roman Hasenkopf Ointment, useful e.g. for treating salt deficiency, acute and chronic trauma, comprises ointment base and homeopathically diluted mineral salt including e.g. calcium phosphate, iron phosphate, potassium chloride and potassium phosphate
US20180243332A1 (en) * 2010-07-22 2018-08-30 Reven Pharmaceuticals, Inc. Method of treating or ameliorating skin conditions with a magnetic dipole stabilized solution

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