WO2019182975A1 - Formulations comprenant des acides alpha hydroxy et procédés d'administration pour la réduction et l'élimination d'inflammations induites par des agents pathogènes dans le corps humain - Google Patents

Formulations comprenant des acides alpha hydroxy et procédés d'administration pour la réduction et l'élimination d'inflammations induites par des agents pathogènes dans le corps humain Download PDF

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Publication number
WO2019182975A1
WO2019182975A1 PCT/US2019/022755 US2019022755W WO2019182975A1 WO 2019182975 A1 WO2019182975 A1 WO 2019182975A1 US 2019022755 W US2019022755 W US 2019022755W WO 2019182975 A1 WO2019182975 A1 WO 2019182975A1
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formulation
carrier composition
high purity
percent
delivery
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PCT/US2019/022755
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English (en)
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Jaim Nulman
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Jaim Nulman
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208—Tissues; Wipes; Patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0063—Periodont
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations

Definitions

  • the present disclosure relates to the treatment of pathogen induced inflammations in the human body.
  • the present disclosure provides formulations and methods for delivery of Alpha Hydroxy Acids as an active therapeutic media to inhibit nucleation sites and thus inhibit reproduction of the pathogens, hence eliminating the inflammation thereof of tissues in the human body and any mammal species.
  • microbiofilms a sticky conglomeration of pathogens
  • pathogens nucleate and are sequestered in these microbiofilms as they provide a mechanically stabile platform for the pathogens to nucleate on, resulting in inflammation of the tissue underlying the biofilm.
  • Formation of a biofilm takes place in several stages, starting with rapid surface attachment, followed by multilayered bacterial cell proliferation, and intercellular adhesion in an extracellular polysaccharide matrix.
  • the presence of these microbiofilms presents three major problems. First, pathogen communities on these surfaces represent a reservoir of pathogens that can be shed into the body, leading to a chronic infection.
  • these microbiofilms are shielded from attack by the human immune system and are often much harder to kill with medicines than their free-floating counterparts; therefore, once these pathogen communities form, they are extremely difficult to eliminate with conventional antimicrobial therapies.
  • host responses and antimicrobial therapies are often unable to eliminate pathogen growth in a biofilm, and chronic inflammatory response at the site of the biofilm results.
  • Identification of these microbiofilms requires advanced analytical techniques such as electron and laser microscopy, hence tissue or organ removal.
  • lymphoid tissue such as adenoids and tonsils, are commonly removed via surgery, and they have provided clear evidence of the presence of these microbiofilms.
  • pathogens External introduction of pathogens to the body. This takes place via one of the following channels: airborne pathogens introduced via the nose and mouth; pathogens that come in contact with food and hands, then introduced by ingestion through the mouth; via the urinary system; and via implant of medical devices such as orthopedic implants, teeth implants, and catheters.
  • pathogens are part of the local microbiome, which is an internal complex balanced ecosystem of bacteria within the human body. The vast majority of the microbiome is located in the digestive system. It is understood that disrupting the microbial ecosystems can cause diseases and weight gain. In addition, some diseases disrupt the human body microbial system, and this disruption is typically triggered by the type of foods eaten. The internal migration of pathogens is exacerbated by the inflammation on all or part of the internal systems due to the presence of pathogens in areas where they should not be, resulting in a biological imbalance in the different sections of these system.
  • a microbiofilm is formed serving as nucleation site for additional pathogens resulting in inflammation of the tissues covering/forming several systems in the human body.
  • the inflammation of these systems results in the inability of the body system to properly function, as well as discomfort and pain in the individual experiencing the inflammation and infection.
  • the inflammation and infection can result in severe diseases such as cancer.
  • Staphylococcus comprises up to two-thirds of all pathogens in orthopedic implant infections and they are the principal causative agents of two major types of infection affecting bone: septic arthritis and osteomyelitis, which involve the inflammatory destruction of joint and bone.
  • Other areas of the human body that are susceptible to pathogen induced microbiofilms include the upper respiratory, digestive, and urinary systems.
  • the digestive system includes, as a partial list, the esophagus, the mouth of the stomach, lymphoid tissues, teeth gums, etc.; the urinary system includes the uterine cervix, urinary bladder, biliary track, etc.; while the upper respiratory system includes also lymphoid tissue organs such as adenoids.
  • inflammation thereof can evolve into malignant tumors that become carcinomas.
  • malignant tumors that become carcinomas.
  • esophageal adenocarcinoma the malignant transformation at the end of a spectrum of diseases related to gastroesophageal reflux disease, which has become the most rapidly increasing cancer in the Western world.
  • pathogens either external or internal, enter a section of the digestive or upper respiratory systems, or when certain conditions trigger an imbalance of the microbiome, the pathogens migrate, nucleate and reproduce in these areas resulting in inflammation of the tissue where they take up unwelcomed residency. All of the pathogen induced inflammations result in an increased pathogen population as a consequence of the increased surface area for pathogen nucleation and reproduction.
  • lymphoid tissues located in the esophagus, as well as adenoids and tonsils in the upper respiratory system. While these lymphoid tissues commonly provide the first line of defense against the external pathogens, they also can become infected and hence inflamed if nucleation conditions exist, hence inhibiting their functionality as well as creating other health problems, such as sleep apnea.
  • bacteria forms in the mouth as a consequence of food residue and ineffective tooth brushing, rinsing or cleaning, hence allowing a bacterial residence in the gums and resulting in accompanying inflammation, yielding what is known as periodontal or gum diseases.
  • a direct consequence of these diseases is damage to the soft gum tissue and bone support for the teeth.
  • an effective and safe treatment that eliminates and further inhibits formation of microfilms, and hence the ability of pathogens to nucleate, thus reducing and even eliminating the inflammation of tissues in the human body, particularly tissues of the digestive, urinary, and upper respiratory systems, as well as tissues surrounding medical device implants such as orthopedic and teeth implants, and resulting from long-term catheter uses, etc.
  • This treatment is accomplished by the use of a formulation based on a-tissue/system-specific carrier for Alpha-Hydroxy Acids (AHAs).
  • AHAs Alpha-Hydroxy Acids
  • the delivery method comprises a procedure that does not result in pain or inflammation of the treated tissue and thus does not interfere with the normal intake of food and liquids, and in general with any other human activity.
  • Figure 1 is a schematic view of the surface of mammalian tissue, such as human body tissue, having a microbiofilm formed thereon and pathogens within the microbiofilm, and a carrier having Alpha Hydroxy Acids dispersed therein being applied to the microbiofilm.
  • Figure 2 is a schematic view of the surface of mammalian tissue, such as human body tissue, having a microbiofilm formed thereon and pathogens within the microbiofilm, and the Alpha Hydroxy Acids dispersed in the carrier having migrated to the microbiofilm and pathogens.
  • Figure 3 is a schematic view of the surface of mammalian tissue, such as human body tissue, showing a protective layer formed thereon.
  • Figure 4 is a schematic view of the interface between the surface of mammalian tissue, such as human body tissue, and a dental implant, wherein a carrier having Alpha Hydroxy Acids dispersed therein is disposed therebetween, such as by forming a coating thereof on the dental implant prior to the deployment thereof into the tissue.
  • a carrier having Alpha Hydroxy Acids dispersed therein is disposed therebetween, such as by forming a coating thereof on the dental implant prior to the deployment thereof into the tissue.
  • Figure 5 is a schematic view of the interface between the surface of mammalian tissue, such as human body tissue, and a dental implant, wherein a protective coating formed from the carrier is formed between the dental implant and the adjacent tissue.
  • Figure 6 is a schematic view of the interface between the surface of mammalian tissue, such as human body tissue, and a dental implant, wherein a carrier having Alpha Hydroxy Acids and an antibiotic dispersed therein is disposed therebetween, such as by forming a coating thereof on the dental implant prior to the deployment thereof into the tissue.
  • a carrier having Alpha Hydroxy Acids and an antibiotic dispersed therein is disposed therebetween, such as by forming a coating thereof on the dental implant prior to the deployment thereof into the tissue.
  • AHAs being a successful developmental method of curbing harsh ageing effects in the skin and cosmeceutical industry.
  • they find their use as food additives, preservatives, and flavoring agents.
  • the use of some AHAs in the medical industry can be traced back to late 1800’s as means to ferment certain bacteria beneficial to the human body, including certain types of Streptococcus bacteria such as the thermophilius CR12; and in the food industry to preserve food longer, especially meats and poultry.
  • AHAs work on the epidermis of the skin by reducing calcium ion concentration and removing calcium ions from the cell adhesions by chelation; this causes disruption in cell adhesions, and results in desquamation.
  • Table 1 lists the AHAs which are used in the pharmaceutical/cosmetic and food industries.
  • AHAs are delivered via a carrier that wets the surface of the tissue to be treated, which AHAs then interact with the surface and subsurface of the treated tissue to remove and/or inhibit the formation of microbiofilms which serve as nucleation sites for pathogens that result in tissue inflammation.
  • the removal of the microbiofilm is accomplished via disruption of the molecular bonds between the tissue and the microbiofilm in the surface and subsurface tissue resulting in dissipation of the non-bonded molecules of the microbiofilm, i.e., the removal, shrinkage and ultimate disappearance of the microbiofilm.
  • the microbiofilm 10 in one or more layers totaling on the order of 1 to 200 microns thick is present on tissue 20, such as digestive tract, upper respiratory tract, or urinary tract tissue.
  • a carrier 40 having the AHA 30 distributed therein, is coated over the microbiofilm 10, and pathogens 50 present therewith, present on the surface of tissue 20. After the carrier 30 is coated on the tissue 20, the AHA therein migrates to and into the pathogen 50-microbiofilm 10 modified surface of the tissue 20 as shown in Figure 2.
  • the AHA formulation interacts with the natural surface of the tissue 20 to disassociate the microbiofilms, thereby allowing the body’s natural fluids and lymphocytes to remove the broken- down portions of microbiofilm and pathogens from the tissue as shown in Figure 3. Additionally, the AHA interacts with the surface of the tissue 20 in such a way that microbiofilms do not again form thereon, and hence pathogens cannot nucleate, reducing and even eliminating the recurrence of infection and inflammation. This is accomplished by the AHA penetrating a few nanometers inwardly of the surface thereof and forming a chemically modified protective layer 60 with surface properties that pathogens cannot nucleate again on. If the formulation is taken orally, the AHA in addition reaches the tissues through the blood stream.
  • 2-Hydroxypropanoic acid, 2-Hydroxypropane- 1 ,2,3-tricarboxylic acid, and 2-Hydroxyethanoic acid are used for the purpose of the present disclosure imbedded in a non-active carrier.
  • Typical AHA formulation consists of both the 2-Hydroxypropanoic acid and the 2-Hydroxypropane-1 ,2,3- tricarboxylic acid, where the primary function is affecting and eliminating the microbiofilms and create subsequent surface modification to eliminate future pathogen nucleation, however an AHA formulation composed of a single one of the materials disclosed in Table 1 is also contemplated herein.
  • the 2- Hydroxypropane-1 ,2,3-tricarboxylic acid also provides molecular binding not only to the carrier but also to the treated surface due to its carboxylic properties that enables an effective chelation function, thus enhancing the effect of the 2- Hydroxypropanoic acid as it is the stronger of the two acids in effecting the removal of the microbiofilms and the subsequent surface adjustment to eliminate further pathogen nucleation.
  • the chelation action can be further enhanced by adding calcium to the formulation up to 10% of the 2-Hydroxypropane-1 ,2,3-tricarboxylic acid concentration. Due to having the smallest molecule size, the 2- Hydroxyethanoic acid is used in addition to the other two acids in order to aid the treatment in extreme cases. Table 2 list the overall and preferable concentration ranges for these three acids.
  • AHA can be delivered to the human body via ingestion of the formulation incorporated in a carrier.
  • localized or tissue specific deliveries are more effective.
  • the carrier is a biodegradable polymer 80 that incorporates the AHA formulation 90.
  • This polymer is coated onto the medical device implant and is an integral part of the implant.
  • the biodegradable polymer releases the AHA molecule which in turn interacts with the surface of the tissue 20 by penetrating inwardly of the tissue surface thereof.
  • this interaction forms a protective layer 60 in such a way that microbiofilms do not form thereon, and hence pathogens cannot nucleate, reducing and even eliminating the occurrence of infection and inflammation.
  • antibiotics 100 can also be included in the biodegradable polymer in order to eliminate the pathogens that are introduced into the surface of the implanted medical device or the exposed tissue during the implant procedure, such as already used by the industry.
  • the delivery of the AHA is here accomplished by either direct application of a water based solution of the AHA or by ingestion of the AHA in a carrier.
  • a water based solution of the AHA or by ingestion of the AHA in a carrier.
  • high purity sterile water or high purity sterile water with up to 10% glucose solution, and preferable in the 3 to 6% range as the carrier for the AHAs is used.
  • the formulation can also be delivered impregnated in a physical application carrier such as a hygienic paper towel , sponge or tampon which is sealed in an air tight and moisture barrier enabled enclosure until its use is needed; then this application carrier is applied by hand to the vagina, two to three times a day for a period of 3 to 6 weeks, preferably four weeks.
  • a catheter can be used to introduce 1 to 100ml, preferable 5 to 20ml of the formulation two to three times a day for a period of 2 to 6 weeks preferable 3 weeks.
  • a manual compression pump is used at the external end of the catheter to push the AHA formulation in the urethra.
  • An alternative method is the use of a three (3) way catheter where the solution is introduced by the use of a soft mechanical pump or a manual compression pump, the solution circulates into the affected area and is then cycled out via the out channel of the catheter.
  • the AHA formulation is delivered via spraying of the formulation into the nostrils.
  • the AHA formulation uses high purity sterile water or high purity sterile water with up to 10% glucose, preferable in the 3 to 6% range as the carrier.
  • the spray is applied two to three times a day for a period of 3 to 6 weeks, preferably four weeks. Ingestion of the AHA in a carrier is also possible and the AHA arrives via the blood stream.
  • the AHA is delivered integrated with tooth paste or mouth wash, either as AHA itself dispersed in the tooth paste or mouth wash, or in a carrier such as a biodegradable polymer or other carrier in the tooth paste or mouth wash .
  • the tooth paste or mouth wash carriers with the AHA can be for regular daily use as a prophylactic against infection, in which case the formulation uses the low end of the preferred concentrations in table 2 providing an ongoing protection against bacteria accumulation.
  • a medicinal tooth paste or mouth wash is provided in the sense of using the higher concentrations listed in Table 2.
  • the medicinal toothpaste or mouth wash is applied two times a day for a period of 6 weeks.
  • the formulation consists typically of a high viscosity high purity inert syrup, no vitamins, and no medical active ingredients, as the carrier for the AHAs.
  • the high viscosity syrup enables the formulation to reside for a maximum time in the inflamed areas of the upper esophagus and the tonsils; it is applied by drinking a tablespoon of the syrup twice daily over a period between 3 to 6 weeks, and preferably for four weeks.
  • the syrup is typically high purity water containing high glucose concentration to yield a Brix between 70 and 90 and typically 85, with a density greater than 1.20g/ml, and typically 1.32 g/ml.
  • the syrup used in the formulation may also be flavored in order to enhance the drinkability thereof by a human. Results of testing with these formulations have shown reduction of the upper esophagus lymphatic tissue organs inflammations and eventual elimination of these inflammations as sown by non-recurrence over a period of more than five years,
  • Table 3 Upper esophagus lymphatic tissue organ size prior and after treatment, and number of re-occurrences of inflammation over a period of 5 years of 1.21 after the treatment, an average organ size reduction by a factor of 383.
  • the non-re-occurrence data is an indication of the surface modification that inhibits the microbiofilm formation and the resultant subsequent pathogen nucleation reduction or rejection.
  • the formulation consisted of 10% 2- Hydroxypropanoic acid, with 2% 2-Hydroxypropane-1 ,2,3-tricarboxylic acid in a berry flavored syrup with a brix of 85 and a density of 1.32g/ml, taken a table spoon two times a day for a month.
  • the formulation consists typically of a medium viscosity high purity inert syrup, no vitamins and no medical active ingredients, as the carrier for the AHAs.
  • the medium viscosity syrup enables the formulation to reside a maximum time along the inflamed areas of the middle to lower sections of the esophagus as well as the valve of the stomach. It is typically applied by drinking a tablespoon of the syrup twice daily over a period between 3 to 6 weeks, and preferable four weeks.
  • the syrup is made of high purity water containing medium glucose concentration to yield a Brix between 40 and 70 and typically 55, with a density in the 0.8g/ml to 1 20g/ml, and preferable 0.9 to 1 .0.
  • the syrup used in the formulation may also be flavored in order to enhance the drinkability thereof by a human.
  • inflammation of other portions of the upper respiratory, urinary, and the digestive systems, other parts of the human body, as well as other medical implants can be also treated with the AHA formulations described here, and also alternative methods for delivery of the AHA formulations can be used including alternative methods to glucose for adjusting the viscosity of the delivery carrier such as ones made out of starch, maple syrup, etc.
  • alternative methods for delivery of the AHA formulations can be used including alternative methods to glucose for adjusting the viscosity of the delivery carrier such as ones made out of starch, maple syrup, etc.
  • Soft gels with outer excipient coatings that release the formulation based on internal body temperature and/or location of the body as affected by presence of other acids/chemicals such as the difference in ambient chemistry between the stomach and the small and large intestines. This can be augmented by time release compounds commonly used in the pharmaceutical industry.
  • the outer excipient coating can also be applied at the AHA molecular level, where temperature/time release methods are used to expose the AHA to the treated surface.

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  • Animal Behavior & Ethology (AREA)
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Abstract

L'invention concerne une formulation constituée d'au moins un acide Alpha-Hydroxy dans une composition de support utile pour le traitement d'une inflammation résultant de la présence de microbiofilms sur des tissus du corps humain où des agents pathogènes se nucléent et se reproduisent. Les acides Alpha-Hydroxyde interfèrent avec la formation et l'entretien de biofilms sur un tissu corporel dans lequel des agents infectieux sont autrement protégés.
PCT/US2019/022755 2018-03-20 2019-03-18 Formulations comprenant des acides alpha hydroxy et procédés d'administration pour la réduction et l'élimination d'inflammations induites par des agents pathogènes dans le corps humain WO2019182975A1 (fr)

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US62/645,651 2018-03-20

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Publication number Priority date Publication date Assignee Title
WO2001022838A1 (fr) * 1999-09-24 2001-04-05 Societe Des Produits Nestle S.A. Eau, jus, boissons et autres aliments liquides enrichis de calcium/calcium-magnesium
US20120070476A1 (en) * 2009-05-29 2012-03-22 Moench Thomas R Compositions and Methods for Inactivation of Pathogens at Genital Tract Surfaces
JP2012211104A (ja) * 2011-03-31 2012-11-01 Ezaki Glico Co Ltd 口臭抑制用組成物
WO2015099754A1 (fr) * 2013-12-27 2015-07-02 Colgate-Palmolive Company Compositions prébiotiques de soin buccal contenant des acides carboxyliques
CN104352358A (zh) * 2014-12-11 2015-02-18 天津市中科健新材料技术有限公司 一种洁阴湿巾液及其制备方法
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