LU102887B1 - Composition and antibacterial usage thereof - Google Patents

Composition and antibacterial usage thereof Download PDF

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Publication number
LU102887B1
LU102887B1 LU102887A LU102887A LU102887B1 LU 102887 B1 LU102887 B1 LU 102887B1 LU 102887 A LU102887 A LU 102887A LU 102887 A LU102887 A LU 102887A LU 102887 B1 LU102887 B1 LU 102887B1
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Luxembourg
Prior art keywords
acid
composition
glycine
hippuric
valine
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LU102887A
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German (de)
Inventor
Xuechen Tian
Siew Woh Choo
Li Chen
Kunping Song
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Wenzhou Kean Univ
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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
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A01N37/04—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof polybasic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A01N37/46—N-acyl derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/42—Preservation of non-alcoholic beverages
    • A23L2/44—Preservation of non-alcoholic beverages by adding preservatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
    • A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
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    • A23L3/3463—Organic compounds; Microorganisms; Enzymes
    • A23L3/3481—Organic compounds containing oxygen
    • A23L3/3508—Organic compounds containing oxygen containing carboxyl groups
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
    • A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
    • A23L3/3454—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals in the form of liquids or solids
    • A23L3/3463—Organic compounds; Microorganisms; Enzymes
    • A23L3/3526—Organic compounds containing nitrogen
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic 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
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic 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
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • 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
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/48—Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
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    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
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    • C11D7/00—Compositions of detergents based essentially on non-surface-active compounds
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    • C—CHEMISTRY; METALLURGY
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    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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Abstract

The invention relates to a composition and an antimicrobial application of a composition. A composition according to the invention is used in the human body or in the environment in which the human body is located, in order to be able to lower the proliferation tendency of microorganisms present in this environment. An antimicrobial application according to the invention is used as an additive in a detergent or fungicide.

Description

English Application Document ZHI0001PLU LU102887
COMPOSITION AND ANTIBACTERIAL USAGE THEREOF
BACKGROUND OF THE INVENTION Technical Field
[0001] The present invention relates to antibacterial agent, and more particularly to a composition and its antibacterial usage. Description of Related Art
[0002] “Immortal Formula Life-Giving Beverage” recorded in “Complete Effective Prescriptions for Women’s Diseases” compiled by Zi-Ming Chen in the Song dynasty of China is a Chinese medicine formula using pangolin. The effects of the full formula include clearing heat, resolving toxins, reducing swelling, breaking nodules, promoting blood circulation, relieving pain and so on for treating pyogenic local infections and other symptoms when carbuncles ulcers initially arise. “Compendium of Materia Medica” compiled by Shi-Zhen Li in the Ming dynasty of China also recites pangolins as a crude drug that serves to cure miasmatic malaria, to eliminate phlegm malaria with alternating sensations of cold and heat, to reduce wandering arthritis with stiffness, to open the passage through the conduits and vessels, to dissolve swelling associated with obstruction-illness, to drain pus and blood, to open the orifices, and to kill bugs. A composite formula made by roasting and grinding clam shell powder and pangolins together is claimed to be effective in curing diarrhea and tenesmus. These are just some examples of ancient Chinese medicine formulas using pangolins to treat illnesses that are believed to be bacterial in the modern medical science. As reported by Yi Guo, et al, in “Journal of Hunan College of Traditional Chinese Medicine,” water decoction made using pangolin scales has antibacterial effects on 11 bacteria, including Escherichia coli, wherein the main component of the water decoction is scale.
[0003] However, pangolins are now threatened, with 8 species thereof listed in IUCN Red List of Threatened Species by the International Union for Conservation of Nature (IUCN) in 2014, and listed in CITES Appendix I by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) signed by China in 2016 as species to be globally protected from trade. In response to the worldwide consensus, “Pharmacopoeia of the People’s Republic of China” has removed pangolins for medical use since 2020. This, therefore, brings about the need of identifying what is the constituent or the combination of constituents contributive to the 1 mm. LE
English Application Document ZHI0001PLU LU102887 antibacterial activity of pangolin scales and artificially synthetizing a substitute that ensures intact therapeutical effects without using pangolin, thereby helping preserve this threatened animal.
[0004] Organic acids are common additives extensively used in various manufacturing applications. Therein, citric acid is the most frequently used one for its effects in preservation and flavor enhancement. For example, Chinese Patent No. CN108670897B discloses an efficient bacteriostatic wet tissue composition and preparation method thereof. The materials of the efficient antibacterial wet tissue composition comprise, by weight, 1-6 parts of ethanol, 0.5-3 parts of butanediol, 0.2-0.6 part of solubilizer, 0.01-0.02 part of menthol, 0.1-0.12 part of fragrance, 0.5-1.0 part of tea extract, 0.5-1.0 part of olive leaf extract, nano-silver, 0.5-1.0 part of purslane extract, 0.1-0.2 part of citric acid, 0.05-0.15 part of sodium citrate and 0.01-0.05 part of phenoxyethanol. This known composition uses organic citric acid as a bacteriostatic additive and uses phenoxyethanol to solubilize citric acid. However, among numerous of organic acids, citric acid is not the most efficient one for bacteriostatic use.
[0005] Hence, the inventors of the present invention made investigation into pangolin scales through scientific experiments to reveal its bacteriostatic constituents, with the attempt to use a combination of multiple weak acids as a bacteriostatic substitute of pangolin scales.
[0006] In addition, on one hand, there are differences in the understanding of those skilled in the art; on the other hand, the applicant has studied a large number of documents and patents when making the present invention, not all the details and content are listed in their entirety. This does not indicate that the present invention does not have the features of these prior art. On the contrary, the present invention has all the features of the prior art, and the applicant reserves the right to add related prior art to the background.
SUMMARY OF THE INVENTION
[0007] In view of the shortcomings of the prior art, the present disclosure provides a composition, which is used in the human body or an environment that the human body is present in, for reducing the reproductive tendency of microorganisms existing in the human body or in the environment. The composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
[0008] Preferably, the components of the composition include: (1) malic acid: (2) hippuric acid; 2
English Application Document ZHI0001PLU LU102887 (3) at least one group, optionally selected, of the following weak acidic components: (1) fumaric acid and/or glycine, (2) succinic acid and/or L-valine.
[0009] According to one preferred embodiment, a first constituent composed of malic acid, hippuric acid, succinic acid, and L-valine is formulated with a second constituent composed of fumaric acid or succinic acid to form the composition that has growth-inhibiting effects on the microorganisms.
[0010] The technical solution of the present invention has the following advantages: as compared to the administration of a single organic acid, a combination of multiple organic acids provides better bacteriostatic effects (as demonstrated in some bacteriostatic experiments), and is more adaptive to different applications such as food, cosmetics, and oral cleaning by adjusting the organic acids used according to desired preservative, deodorizing, refreshing uses. Formation and decomposition of organic acids are harmless to both human bodies and the environment. Organic acids enter bacteria in the form of small molecules and may destroy the alkaline environments inside bacteria, thereby inhibiting bacterial activity. Organic acids in a combination form covalent structures with each other, and increase bacteriostatic effects of each other, Opposite to the prior-art solutions where a single organic acid or a random combination of organic acids is used in a large amount to be effective, the present invention uses relatively small amounts of organic acids to form a composition, thereby preventing damage to human bodies that caused by excessive use of preservative additives in food.
[0011] According to one preferred embodiment, the composition acting in the human body or in the environment comprises malic acid, hippuric acid, glycine, and citric acid, wherein the composition, by virtue of interaction between malic acid and citric acid, is able to enhance a fruity aroma component in the environment.
[0012] According to one preferred embodiment, the composition at least comprises malic acid, hippuric acid, glycine, and citric acid, wherein components forming the composition are administered to a skin surface of the human body in the form of a non-Newtonian fluid.
[0013] According to one preferred embodiment, the composition at least comprises malic acid, hippuric acid, glycine, and fumaric acid, wherein the components forming the composition are administered to a skin surface of the human body in the form of a non-Newtonian fluid. 3 ms LE
English Application Document ZHI0001PLU LU102887
[0014] The technical solution of the present invention also has the following advantages: fluid drugs and cosmetics for repairing, treating or protecting skin surface tend to be too mobile to stay firmly in place after applied, yet paste-like ones tend to be too sticky to be applied evenly. The composition of the present invention is in the form of a non-Newtonian fluid, which is less mobile at a given viscosity, thereby ensuring the components can stay in place on human face and skin firmly.
[0015] According to one preferred embodiment, the composition is able to inhibit reproduction of Gram-positive bacteria and Gram-negative bacteria through synergy.
[0016] A composition, wherein the composition constitutes, in a dispersed phase and with a friction agent, a cleaning component of an oral cleaning agent, wherein the composition serves to inhibit growth of Gram-negative bacteria and Gram-positive bacteria, as represented by Escherichia coli and Staphylococcus aureus, respectively, wherein the composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
[0017] A composition, being able to inhibit reproduction of Gram-negative bacteria and Gram- positive bacteria that exist on a skin surface of a human body or in food, as represented by Escherichia coli and Staphylococcus aureus, respectively, wherein the composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
[0018] Antibacterial usage of a composition, comprising using the composition as an additive to be added into a detergent or a bactericide, wherein the composition used as the additive includes a first composition part that releases H* and a second composition part that increases bactericidal effects and active duration of the composition, wherein the first composition part comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid, and the second composition part comprises hydrocolloid, wherein when the composition serving as an additive is administered, the first composition part interlaces into the second composition part, and works with the second composition part to coat Gram- negative bacteria and Gram-positive bacteria as represented by Escherichia coli and Staphylococcus aureus, respectively, carried by a subject to which the detergent or the 4 | ———————————————————————
English Application Document ZHI0001PLU LU102887 bactericidal drug is administered and thereby acts in the interior of the bacteria.
[0019] Antibacterial usage of a composition, comprising using the composition as a drug for treating bacterial infection, wherein the drug primarily comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
DETAILED DESCRIPTION OF THE INVENTION
[0020] The present invention will be described in detail with reference to some embodiments.
[0021] The present invention provides a bacteriostatic composition, which is particularly effective in inhibiting microorganisms as represented by Escherichia coli and Staphylococcus aureus.
[0022] Organic acids used in the bacteriostatic composition may include fumaric acid, succinic acid, L-valine, malic acid, citric acid, glycine, and hippuric acid. Their proportions in the bacteriostatic composition are consistent with those in pangolin scales. Therein, in the total extraction (CV), fumaric acid accounts for 0.1%; succinic acid accounts for 0.4%; L-valine accounts for 1.3%; malic acid accounts for 1.2%; citric acid accounts for 0.2%; glycine accounts for 0.1%; and hippuric acid accounts for 0.3%. Preferably, the composition remains effective after certain adjustments of the foregoing proportions.
[0023] For the purpose of the present invention, the microorganisms may comprise Gram- negative bacteria, Gram-positive bacteria, pathogenic Staphylococcus as represented by Staphylococcus aureus, opportunistic pathogens as represented by Escherichia coli, and other pathogenic bacteria, such as Mycobacterium tuberculosis.
[0024] For the purpose of the present invention, the organic acids used to conduct experiments and to form the disclosed composition are all artificially synthesized.
[0025] The present invention uses components with highly different proportions to form a composition that provides better bacteriostatic effects than a single component or a combination of a few components of the same volume.
Embodiment 1 5 mets
English Application Document ZHI0001PLU LU102887
[0026] A bacteriostatic experiment was conducted based on the minimum inhibitory concentration (MIC) method to estimate the minimum inhibitory concentrations (MICs) of the foregoing antibacterial metabolite against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Serratia marcescens (S. marcescens). (1) Experiment Materials: 1) Medium The medium used for culture was lysogeny broth (LB), containing 10g/L of peptone, 5g/L of a yeast extract, and 10g/L of sodium chloride. 2) Antibacterial Drug: All compositions that comprise one or more of fumaric acid, succinic acid, L-valine, malic acid, citric acid, glycine, and hippuric acid were used as the antibacterial drug. (2) Steps of Bacteriostatic Experiments: 1) Preparation of Bacterial Suspension
[0027] The stored Escherichia coli as a representative of Gram-negative bacteria and Staphylococcus aureus as a representative of Gram-positive bacteria were resuscitated simultaneously. Individual colonies of diameter about 1 mm were picked up from a plate of isolated strains of the species to be tested using an inoculation ring and immobilized in 2 mL of LB broth before cultured at 37°C in a biochemical incubator. The culture in the log-growth phase with increased strains was corrected to a concentration of 0.5 McFarland Equivalence Turbidity Standards (or having absorbance of 0.08 to 0.10 at 625 nm) using LB broth, containing about 1x108 to 2x108 CFU mL". 2) Preparation of Antibacterial Drugs
[0028] The two-fold dilution method was used to prepare composite antibacterial drugs having concentrations of 4C, 2C, C, 0.5C, 0.25C, 0.125C, 0.0625C, and 0.03125C. Specifically, 8 sterile test tubes are numbered in series, and 1ml of sterile water was added into test tubes Nos. 2-8, respectively. In the first test tube, 2ml of 4C antibacterial drug was prepared. One ml of the solution in the first test tube was added into the second test tube and well mixed. The 1ml of the solution in the second test tube was added into the third test tube. Dilution was made in sequence and so on. 3) Measurement of MIC
[0029] In the first line of a 96-well plate, 200uL of LB broth medium was added to form a 6
English Application Document ZHI0001PLU LU102887 negative control, and in each of the 2-10 lines, 180pL of the prepared bacterial suspension was added to reach a final concentration of 1x10° CFU-mL"!. In the second line, 20uL of sterile water was added to form a positive control. In each of lines 3 to 10, 20uL of drug was added, making the final concentrations reach 0.4, 0.2, 0.1, 0.05, 0.025, 0.0125, 0.00625, and 0.003125C, respectively. The post-inoculation plate was then cultured at 37°C for 24h. The LB broth media were observed for turbidity and OD values were measured to determine the MIC values. The experiment was made triplicate.
[0030] The MICs of each tested metabolite against Escherichia coli and Staphylococcus aureus are shown in Table 1. To summarize, among the individual antibacterial metabolites, malic acid is the one exhibiting the best inhibitory effects on Escherichia coli and Staphylococcus aureus. -_— Metabolite — ME E. coli S. aureus Fumaric Acid 25C 25C Succinic Acid C C Malic Acid 0.25 C 0.25 C Citric Acid 1.25 C 1.25 C L-Valine 2.5C 25C Glycine 10C 10C Hippuric Acid C C Table 1
[0031] For proving the optimal effects of malic acid and its composition, a bacteriostatic experiment was further conducted on compositions made of malic acid and other metabolites. The results represented by MIC values are listed in Table 2. -_— Metabolite Combination Me E. coli S. aureus Malic Acid +Fumaric Acid 0.2C 02C Malic Acid +Succinic Acid 0.2C 02C Malic Acid +Citric Acid 02C 02C Malic Acid +L-Valine 02C 02C Malic Acid +Glycine 02C 02C 7
English Application Document ZHI0001PLU LU102887 Malic Acid +Hippuric Acid 02C 02C Table 2
[0032] As demonstrated by the results, the binary compositions containing malic acid resulted in reduced MIC values against Escherichia coli and Staphylococcus aureus, indicating that they had increased inhibitory effects on both bacterial species. Furthermore, a bacteriostatic experiment was conducted using ternary compositions with random assignments, and the results are listed in Table 3.
MIC Metabolite Combination - E coli S. aureus Malic Acid +Fumaric Acid +Succinic Acid 02C 02C Malic Acid +Fumaric Acid +L-Valine 04C 04C Malic Acid +Fumaric Acid +Citric Acid 04C 04C Malic Acid +Fumaric Acid +Glycine 02C 02C Malic Acid +Fumaric Acid +Hippuric Acid 02C 02C Malic Acid +Succinic Acid +L-Valine 0.2C 02C Malic Acid +Succinic Acid +Citric Acid 02C 02C Malic Acid +Succinic Acid +Glycine 02C 02C Malic Acid +Succinic Acid +Hippuric Acid 0.2C 02C Malic Acid +L-Valine +Citric Acid 02C 02C Malic Acid +L-Valine +Glycine 04C 04C Malic Acid +L-Valine +Hippuric Acid 0.4 C 04C Malic Acid +Glycine +Hippuric Acid 0.2C 02C Malic Acid +Glycine +Citric Acid 02C 04C Malic Acid +Hippuric Acid +Citric Acid 0.1C 02C Table 3
[0033] The composition of malic acid and fumaric acid when combined with L-valine or citric acid had rebounded, decreased bacteriostatic effects. Similarly, malic acid and L-valine when combined with glycine or hippuric acid also had reduced inhibitory effects on Escherichia coli and Staphylococcus aureus and the MIC value returned to 0.4C. The composition of malic acid, hippuric acid, and citric acid showed the best inhibitory effects on Escherichia coli, with the MIC 8
English Application Document ZHI0001PLU LU102887 value of 0.1C.
[0034] Moreover, with malic acid chosen as the major component, other metabolites and malic acid were combined to form four compositions for an additional bacteriostatic experiment, whose results are shown in Table 4 below. Metabolite Combination ME E. coli S. aureus © Malic Acid +Fumaric Acid +Succinic Acid +L-Valine 02C 02C Malic Acid +Fumaric Acid +Succinic Acid +Citric Acid 0.2 C 0.2C Malic Acid +Fumaric Acid +Succinic Acid +Glycine 02C 02C Malic Acid +Fumaric Acid +Succinic Acid +Hippuric Acid 0.2 C 02C Malic Acid +Fumaric Acid +L-Valine +Citric Acid 02C 02C Malic Acid +Fumaric Acid +L-Valine +Glycine 04C 04C Malic Acid +Fumaric Acid +L-Valine +Hippuric Acid 0.2 C 02C Malic Acid +Fumaric Acid +Citric Acid +Glycine 0.2C 0.2C Malic Acid +Fumaric Acid +Citric Acid +Hippuric Acid 0.2 C 02C Malic Acid +Fumaric Acid +Glycine +Hippuric Acid 0.1C 0.1C Malic Acid +Succinic Acid +L-Valine +Citric Acid 02C 02C Malic Acid +Succinic Acid +L-Valine +Glycine 02C 02C Malic Acid +Succinic Acid +L-Valine +Hippuric Acid 02C 02C Malic Acid +Succinic Acid +Citric Acid +Glycine 02C 0.2C Malic Acid +Succinic Acid +Citric Acid +Hippuric Acid 0.2C 02C Malic Acid +Succinic Acid +Glycine +Hippuric Acid 0.2 C 02C Malic Acid +L-Valine +Citric Acid +Glycine 04C 04C Malic Acid +L-Valine +Citric Acid +Hippuric Acid 02C 02C Malic Acid +L-Valine +Glycine +Hippuric Acid 04C 04C Malic Acid +Citric Acid +Glycine +Hippuric Acid 0.1C 0.1C Table 4
[0035] As demonstrated by the results, the composition of malic acid, fumaric acid, glycine, and hippuric acid and the composition of malic acid, citric acid, glycine, and hippuric acid provided the best bacteriostatic effects, with the MIC values down to 0.1C. 9
English Application Document ZHI0001PLU LU102887
[0036] Also, with malic acid as the major components, other metabolites and malic acid were combined to form five compositions for a further bacteriostatic experiment whose results are shown in Table 5. Metabolite Combination 0 MIE E. coli S. aureus Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Citric Acid 02C 02C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Glycine 02C 02C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Hippuric Acid 0.1C 02C Malic Acid +Fumaric Acid +L-Valine +Citric Acid +Glycine 02C 02C Malic Acid +Fumaric Acid +L-Valine +Citric Acid +HippuricAcid O1C 0.1 C Malic Acid +Fumaric Acid +L-Valine +Glycine +Hippuric Acid 0.1C 02¢C Malic Acid +Fumaric Acid +Citric Acid +Glycine +Hippuric Acid 01C 0.1 C Malic Acid +Succinic Acid +L-Valine +Citric Acid +Glycine 02C 02C Malic Acid +Succinic Acid +L-Valine +Citric Acid +Hippuric Acid O1C 0.1 C Malic Acid +Succinic Acid +L-Valine +Glycine +Hippuric Acid 01C OIC Malic Acid +Succinic Acid +Citric Acid +Glycine +Hippuric Acid 0.1C 0.1 C Malic Acid +L-Valine +Citric Acid +Glycine +Hippuric Acid 01C 02C Table 5
[0037] As demonstrated by the results, the three compositions made of malic acid, L-valine, citric acid, glycine, hippuric acid; malic acid, fumaric acid, succinic acid, L-valine, hippuric acid; and malic acid, fumaric acid, L-valine, glycine, hippuric acid, respectively, exhibited bacteriostatic effects on Escherichia coli with MIC values of 0.1C. All the compositions of malic acid, succinic acid, L-valine, glycine, hippuric acid; malic acid, fumaric acid, L-valine, citric acid, hippuric acid; malic acid, fumaric acid, citric acid, glycine, hippuric acid; malic acid, succinic acid, L- valine, citric acid, hippuric acid; and malic acid, succinic acid, citric acid, glycine, hippuric acid showed bacteriostatic effects on Escherichia coli and Staphylococcus aureus with the MIC values
0.1C. By contrast, none of the prior-art schemes where only a single organic acid or a combination of two organic acids is used as the additive can be as effective as the disclosed compositions made of four or more organic acids in terms of disinfection.
[0038] By still using malic acid as the major components, the present inventors used seven other 10
English Application Document ZHI0001PLU LU102887 metabolites to formulate six compositions for a further bacteriostatic experiment whose results are shown in Table 6. , MIC Metabolite Combination —_— E. coli S. aureus Malic Acid +Succinic Acid +L-Valine +Citric Acid +Glycine +Hippuric Acid 01C 01C Malic Acid +Fumaric Acid +L-Valine +Citric Acid +Glycine +Hippuric Acid 01C 0.1 C Malic Acid +Fumaric Acid +Succinic Acid +Citric Acid +Glycine +Hippuric Acid 0.1 C¢ 0.1 C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Glycine +Hippuric Acid 0.1C 0.1 C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Citric Acid +Hippuric Acid 01C 0.1¢C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Citric Acid +Glycine 01C 0.1C Malic Acid +Fumaric Acid +Succinic Acid +L-Valine +Citric Acid +Glycine +Hippuric Acid 01C 0.1C _—m—,—————— te Ye Table 6
[0039] As demonstrated by the results, even composed of six or more different metabolites, the resulting components were effective in inhibiting both Staphylococcus aureus and Escherichia coli, with the MIC values of 0.1C.
[0040] Furthermore, the inhibitory effects of a metabolite combination of malic acid, hippuric acid, fumaric acid, and glycine against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens were measured and the results are listed in Table 7: -_— Strain MIC - E. coli 0.1C S. aureus 0.1C P. aeruginosa 02C S. marcescens 02C _ IE Table 7 1
English Application Document ZHI0001PLU LU102887
[0041] As demonstrated by the results, the composition composed of organic acid metabolites of malic acid, hippuric acid, fumaric acid, and glycine showed excellent bacteriostatic effects on Escherichia coli and Staphylococcus aureus, with the MIC value of 0.1C, and had the MIC values of 0.2C with Pseudomonas aeruginosa and Serratia marcescens. It is thus clear that the composition composed of organic acid metabolites of malic acid, hippuric acid, fumaric acid, and glycine is effective in inhibiting such bacteria as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens, and is particularly effective in inhibiting growth of pathogenic bacteria.
[0042] Serratia marcescens is a Gram-negative bacillus, also an opportunistic pathogen.
[0043] Pseudomonas aeruginosa is a Gram-negative bacterium, featuring for opportunistic infection.
[0044] Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens are extensively distributed in the nature, and may enter human bodies through mouths and noses. They may incur pathogenic reactions such as inflammations in human bodies under certain conditions or in certain environments. Therefore, the four species of bacteria were chosen for the bacteriostatic experiments of the present invention.
[0045] According to the experiment results as given above, the composition made of malic acid, glycine, and hippuric acid when combined with citric acid or fumaric acid provided outstanding bacteriostatic effects on Staphylococcus aureus and Escherichia coli, with the MIC value of 0.1C.
[0046] The composition of the present invention may be made of fumaric acid taking up 0.1%, succinic acid taking up 0.4%, L-valine taking up 1.3%, malic acid taking up 1.2%, citric acid taking up 0.2%, glycine taking up 0.1%, and hippuric acid taking up 0.3%. An antibacterial composition is prepared using the above proportions.
[0047] Preferably, the composition for reducing the reproductive tendency of microorganisms present at the surface of a human body or in the environment where the human body is present contains one or more of 0.125% to 0.482% of malic acid, 0.135% to 0.422% of L-valine, 0.021% to 0.081% of citric acid, 0.01% to 0.04% of succinic acid, 0.031% to 0.121% of hippuric acid, 12
English Application Document ZHIO001PLU LU102887
0.001% to 0.041% of glycine, and 0.01% to 0.041% of fumaric acid.
[0048] Preferably, in the composition, the proportions of individual components are: malic acid accounting for 1% to 30% of the total components, L-valine accounting for 0.1% to 20% of the total components, citric acid accounting for 0.1% to 20% of the total components, succinic acid accounting for 0.1% to 20% of the total components, hippuric acid accounting for 0.1% to 20%, glycine accounting for 0.1% to 20% of the total components, and fumaric acid accounting for
0.1% to 20% of the total components.
[0049] Preferably, in the composition, the proportions of individual components are: malic acid accounting for 10% to 40% of the total components, L-valine accounting for 0.01% to 10% of the total components, citric acid accounting for 0.01% to 10% of the total components, succinic acid accounting for 0.01% to 20% of the total components, hippuric acid accounting for 0.01% to 20%, glycine accounting for 0.01% to 20% of the total components, and fumaric acid accounting for 0.01% to 10% of the total components.
[0050] Preferably, in the composition, the proportions of individual components are: malic acid accounting for, in weight, about 0.1% to 20%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20%, 20% to 60% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, 40%, and all ranges or subranges contained therein of the total components.
[0051] Preferably, in the composition, the proportions of individual components are: L-valine accounting for, in weight, about 0.01% to 1%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
[0052] Preferably, in the composition, the proportions of individual components are: citric acid accounting for, in weight, about 0.01% to 2%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
13
English Application Document ZHT0001PLU LU102887
[0053] Preferably, in the composition, the proportions of individual components are: succinic acid accounting for, in weight, about 0.1% to 20%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
[0054] Preferably, in the composition, the proportions of individual components are: hippuric acid accounting for, in weight, about 0.1% to 20%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20%, 20% to 60% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
[0055] Preferably, in the composition, the proportions of individual components are: glycine accounting for, in weight, about 0.1% to 2%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
[0056] Preferably, in the composition, the proportions of individual components are: fumaric acid accounting for, in weight, about 0.1% to 20%, 1% to 10%, 3% to 8%, 6% to 12%, 15% to 18%, 17% to 20% of the total components, or accounting for, in weight, about 1%, 2%, 3%, 4%, 5%, 6%, 7%. 8%, 9%, 10%, 15%, 20%, 30%, or 40%, and all ranges or subranges contained therein of the total components.
[0057] Preferably, the combination proportions of malic acid, L-valine, citric acid, succinic acid, hippuric acid, glycine, and fumaric acid may include but is not limited to the foregoing combination proportions.
[0058] The compositions having inhibitory effects on Escherichia coli with MIC values of 0.1C may be represented by a composition of malic acid, hippuric acid, and citric acid, and the compositions having inhibitory effects on both Escherichia coli and Staphylococcus aureus with MIC values of 0.1C may be represented by compositions of malic acid, fumaric acid, glycine, hippuric acid; and compositions of malic acid, citric acid, glycine, hippuric acid. Since the components forming these compositions are all weak acids and can be absorbed by human bodies 14
English Application Document ZHI0001PLU LU102887 as safe food additives, they are harmless to human bodies so the compositions as described previously can be used in various fields. As known in the art, any of the existing organic acids is bacteriostatic and can be added into food or antiseptics that may have contact with human bodies in such a large amount that allowed by law. However, organic acids when used as additives and added in large amounts can form transmutation products in human bodies. While these products can be metabolized to some extent, when the additives are added in large amounts, metabolism may fail to excrete all these products timely, bringing about the risk of threatening health of human bodies. The present invention provides the optimal bacteriostatic composition by combining organic acids that have good bacteriostatic effects in certain proportions. As compared to the prior art, the present invention uses more kinds of edible organic acids each with a reduced amount, thereby ensuring good preservative effects on food or other products without threatening health of human bodies. Embodiment 2
[0059] The present embodiment provides further improvements to Embodiment 1 and the combination thereof, and repetitive description will be omitted for succinctness.
[0060] Throat Benefiting Lozenge is known as an effective Chinese medicine formulation for treating chronic pharyngitis caused by bacterial infection. It primarily comprises pangolin (processed), ground beetle, stiff silkworm, oyster shell (calcined), and figwort. Therein, the ingredient, pangolin (processed), was obtained from an endangered animal and is now prohibited. Thus, Throat Benefiting Lozenge cannot be used as either a prescription medicine or a non- prescription medicine for treatment. The inventors of the present invention invested into pangolin scales for the inhibitory effects on microbiota, particularly Escherichia coli and Staphylococcus aureus, and found one or more sets of compositions effective in inhibiting Escherichia coli and Staphylococcus aureus. The compositions may primarily comprise one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid. To replace the pangolin ingredient in Throat Benefiting Lozenge, the substitute may be an extract of biological tissue with similar ingredient, or may be an artificially synthesized metabolite having similar bacteriostatic effects. In a preferred implementation where the substitute is an artificially synthesized compound, the substitute is the composition of malic acid, fumaric acid, succinic acid, L-valine, citric acid, and glycine that showed the best inhibitory effects on Gram-negative bacteria as represented by Escherichia coli and Gram-positive bacteria as represented by Staphylococcus aureus in the foregoing experiments. Addition of these organic acids can also 15
English Application Document ZHI0001PLU LU102887 endow the resulting lozenge with fruity flavor welcome by children, thereby enhancing willingness of infants and young children to take the medicine. Embodiment 3
[0061] The present embodiment provides further improvements to Embodiments 1 and 2 and the combination thereof, and repetitive description will be omitted for succinctness.
[0062] The disclosed composition in the present embodiment is also useful as an additive composition for various food products to effectively inhibit Escherichia coli and Staphylococcus aureus in food. For example, to be added into some natural fruit juices, the composition may use certain proportions of malic acid and citric acid to add natural flavor, and can provide predicative effects when working with vacuum or sealed packaging of the fruit juice products by inhibiting growth of Escherichia coli and Staphylococcus aureus. Such an additive primarily comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid. When working alone or in combination, malic acid and citric acid can endow the additive with fruity flavor. Embodiment 4
[0063] The present embodiment provides further improvements to Embodiments 1, 2 and 3 and the combination thereof, and repetitive description will be omitted for succinctness.
[0064] The composition of the present embodiment is for sterilizing use in homes or normal living environments. For example, people in daily live may need to frequently maintain environmental sanitation or disinfect clothing to eliminate bacteria, particularly Staphylococcus aureus that is harmful to human bodies. However, the use of medicinal alcohol and 84 Disinfectant (a solution of sodium hypochlorite) may also bring about harm to human bodies and thus is considered unsafe to pregnant women and children. The present invention is based on the composition composed of weak acid components and incorporates other harmless disinfectant components to form a liquid bactericidal reagent suitable for families with children and/or pregnant women.
[0065] The composition made of organic acids may be used as an additive and added into any detergent or bactericidal agent. The composition acting as an additive is effective in deodorizing and sterilizing clothing and environments. The composition contains a first composition part 16
ZELL
English Application Document ZHI0001PLU LU102887 acting as an acidity or pH regulator and a second composition part for increasing bactericidal effects and active duration. The first composition part comprises either of the following two combinations: (1) malic acid, glycine, hippuric acid, and citric acid; and (2) malic acid, glycine, hippuric acid, and fumaric acid. The second composition part comprises hydrocolloid.
[0066] Hydrocolloid containing polysaccharides and proteins forms a gel network. When the gel network covers the Escherichia coli or Staphylococcus aureus carried by the target to which the detergent or bactericidal agent is applied, the first composition part existing in the hydrocolloid enters the interior of bacteria due to the pressure that the gel network exerts on the bacteria. The first composition part and the second composition part work jointly to form organic acids with synergy, to release H' inside the bacteria, and to break the alkaline environment inside the bacteria, thereby inhibiting the activity of the bacteria. The first composition part is interlaced with the hydrocolloid, and works with the hydrocolloid to act inside Escherichia coli or Staphylococcus aureus carried by the target to which the detergent or bactericidal agent is applied.
[0067] Since the organic acids acting in the intracellular environment of the bacteria have their molecule diameter smaller than channels in the membrane of Escherichia coli and Staphylococcus aureus, the organic acid molecules can enter the interior of the bacteria through the membrane of the bacteria to break the alkaline environment inside the bacteria, thereby inhibiting activity of the bacteria.
[0068] With the synergy between the first composition part composed of malic acid, glycine, and hippuric acid and the second composition part composed of citric acid or fumaric acid, the composition of the present embodiment inhibits growth of Escherichia coli and Staphylococcus aureus. Embodiment 5
[0069] The present embodiment provides further improvements to Embodiments 1, 2, 3 and 4 and the combination thereof, and repetitive description will be omitted for succinctness.
[0070] In the present embodiment, the composition is to be sprayed, atomized or otherwise formed as small particles of gas or liquid and then spread onto the surface of the subject to kill and inhibit Escherichia coli and Staphylococcus aureus on the surface of the subject. 17
English Application Document ZHIO001PLU LU102887
[0071] The composition is composed of combined liquid particles or gas particles. The liquid particles or gas particles each comprise a core formed of highly bacteriostatic organic acids and a coating layer covering the core. The coating layer is composed of a zirconia-tin oxide complex neutralized by a silane coupling agent in a nanoscale, inorganic, micro-porous form for protecting the core and increasing adhesive capacity.
[0072] In use, the zirconia-tin oxide complex covering the organic acid silane coupling agent is distributed on clothing or in living environments in the form of aerosol or small-particle liquid. When the zirconia-tin oxide complex covering the organic acid silane coupling agent contacts Escherichia coli and Staphylococcus aureus on the target surface, the coating breaks under pressure and releases the organic acids. Then the organic acids can penetrate into the interior of bacteria through the membrane of the bacteria, thereby inhibiting the activity of the bacteria. The nanoscale inorganic micro-porous structure of the zirconia-tin oxide complex allows the organic acid molecules to pass therethrough and prevents large-size particles from decomposing the particles and hindering attachment. The zirconia-tin oxide complex can form the outer coating in the form of aerosol, liquid, or gas with desired hardness and toughness that prevent the nano- scale micro-porous structure from collapse.
[0073] Preferably, the silane coupling agent and the zirconia-tin oxide complex in the nanoscale, inorganic, micro-porous form is used at a ratio of 1:40 to 1:120. The zirconia-tin oxide complex in the nanoscale, inorganic, micro-porous form and the organic acids are used at a ratio of 1:1 to 1:10.
[0074] The organics-inorganics composite coupled by a silane coupling agent can move toward the target surface in the form of micro-particles having a diameter at least smaller than 10um. The micro-particles have good dispersion stability in the aqueous phase for diluting or homogenizing the liquid phase. They can carry the organic acids and firmly attach to the target surface. Besides, they can make the organic acid core less volatile by coating it. With the intermediate phase that is low-cost and capable of stably coupling the inner organic layer and the outer inorganic layer, an inorganic layer coupled with but not chemically reacting with the organic layer is added without degrading the ionization of hydrinos in the organic layer. By virtue of the nature of the inorganic layer, problems of the organic layer about inferior attachment to a target surface, inactivity, and high volatility can be solved. Preferably, the coupling caused by the silane coupling agent is aqueous coupling. 18
English Application Document ZHIO001PLU LU102887
[0075] The composition may be prepared as below: (1) Weighting: weighting a silane coupling agent and a zirconia-tin oxide complex (that may exist as aerosol) according to the proportions converted into weight values, and weighting the organic acid composition according to the proportion converted into a volume value; and (2) Mixing: adding the zirconia-tin oxide complex in to organic acids for several times, mixing, and adding the silane coupling agent with agitation, and mixing until the three phases become homogenous, thereby obtaining the concentrated composition.
[0076] The concentrated composition is diluted using water before use and then cab be sprayed onto articles in an environment or clothing to be sterilized by means of an atomizing machine, a sprayer, or a similar device.
[0077] The organic acid(s) at the core of the particle may be the organic acid composition that has bacteriostatic effects on Escherichia coli and Staphylococcus aureus with the MIC value of
0.1C as described in the foregoing embodiments. The organic acid(s) covered and protected by the coating layer has high stability in water and thereby has excellent inhibitory effects on Escherichia coli and Staphylococcus aureus.
Embodiment 6
[0078] The present embodiment provides further improvements to Embodiments 1, 2, 3,4and 5 and the combination thereof, and repetitive description will be omitted for succinctness.
[0079] In the present embodiment, the disclosed organic acid composition that can stay firmly on surfaces and act on bacteria may be made as a bacteriostatic ointment or spray containing one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid, which acts on surface or mucosa of the face, arms, or major organs of a subject. The combination of these organic acids has significant bacteriostatic effects on various pathogenic skin microbes including Gram-negative bacteria and Gram-positive bacteria as represented by Escherichia coli and Staphylococcus aureus, respectively.
[0080] Preferably, the bacteriostatic ointment may comprise Chinese medicine ointment, Chinese medicine powder, mussel adhesive protein, and an organic acid composition made of one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric 19
English Application Document ZHI0001PLU LU102887 acid.
[0081] Preferably, the bacteriostatic spray may comprise pentylene glycol, 1,3-propylene glycol, and an organic acid composition made of one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
[0082] It should be noted that the above specific embodiments are exemplary, and those skilled in the art can come up with various solutions inspired by the disclosure of the present invention, and these solutions also belong to and fall into the scope of the disclosure of the present invention. Those skilled in the art should understand that the description of the present invention is illustrative and do not constitute a limitation to the claims. The protection scope of the present invention is defined by the claims and their equivalents. The description of the present invention contains a number of inventive concepts, terms such as "preferably", "according to a preferred embodiment" or "optionally" all indicate that the corresponding paragraph discloses an independent idea, and the applicant reserves the right to apply for a divisional application based on each inventive idea. In the full text, the feature guided by "preferably" is only an optional method and should not be construed as mandatory. Therefore, the applicant reserves the right to waive or delete relevant preferred features at any time.

Claims (10)

English Application Document ZHI0001PLU LU102887 What is claimed is:
1. À composition, being used in a human body or in an environment where the human body is present to reduce a reproductive tendency of microorganisms existing in the human body or the environment, wherein the composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
2. The composition of claim 1, wherein a first constituent composed of malic acid, hippuric acid, succinic acid, and L-valine is formulated with a second constituent composed of fumaric acid or succinic acid to form the composition that has inhibitory effects on the growth of the microorganisms.
3. The composition of claim 1 or 2, wherein the composition acting in the human body or the environment comprises malic acid, hippuric acid, glycine, and citric acid, wherein the composition, by the interaction between malic acid and citric acid, is able to enhance a fruity aroma component in the environment,
4. The composition of any of claims 1 through 3, wherein the composition at least comprises malic acid, hippuric acid, glycine, and citric acid, wherein components forming the composition are administered to a skin surface of the human body in the form of a non-Newtonian fluid.
5. The composition of any of claims 1 through 3, wherein the composition at least comprises malic acid, hippuric acid, glycine, and fumaric acid, wherein the components forming the composition are administered to a skin surface of the human body in the form of a non-Newtonian fluid.
6. The composition of any of claims 1 through 5, wherein the composition is able to inhibit reproduction of Gram-positive bacteria and Gram-negative bacteria through synergy.
7. A composition, wherein the composition constitutes, in a dispersed phase and with a friction agent, a cleaning component of an oral cleaning agent, wherein the composition serves to inhibit the growth of Gram-negative bacteria and Gram-positive bacteria, as represented by Escherichia coli and Staphylococcus aureus, respectively, wherein the composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
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English Application Document ZHI0001PLU LU102887
8. À composition, being able to inhibit reproduction of Gram-negative bacteria and Gram- positive bacteria that exist on a skin surface of a human body or in food, as represented by Escherichia coli and Staphylococcus aureus, respectively, wherein the composition comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
9. Antibacterial usage of a composition, comprising using the composition as an additive to be added into a detergent or a bactericide, wherein the composition used as the additive includes a first composition part that releases H* and a second composition part that increases bactericidal effects and active duration of the composition, wherein the first composition part comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid, and the second composition part comprises hydrocolloid, wherein when the composition serving as an additive is administered, the first composition part interlaces into the second composition part, and works with the second composition part to coat Gram- negative bacteria and Gram-positive bacteria as represented by Escherichia coli and Staphylococcus aureus, respectively, carried by a subject to which the detergent or the bactericidal drug is administered and thereby acts in the interior of the bacteria.
10. Antibacterial usage of a composition, comprising using the composition as a drug for treating bacterial infection, wherein the drug primarily comprises one or more of malic acid, hippuric acid, fumaric acid, glycine, succinic acid, L-valine, and citric acid.
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LU102887A 2021-10-13 2021-12-16 Composition and antibacterial usage thereof LU102887B1 (en)

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CN113995744B (en) * 2021-10-13 2023-03-17 温州肯恩大学 Composition and antibacterial application thereof
CN115466652A (en) * 2022-09-21 2022-12-13 云南水星生物科技有限公司 Antibacterial color fixative and preparation method and application thereof

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AU1095801A (en) * 1999-10-19 2001-04-30 Procter & Gamble Company, The Antimicrobial compositions comprising a biologically active organic acid
EP1483975A1 (en) * 2003-06-05 2004-12-08 PURAC Biochem BV Antimicrobial composition comprising a mixture of lactic acid or a derivative thereof and an inorganic acid
KR20130123489A (en) * 2012-05-03 2013-11-13 이상현 Microbicide compositions using vitamin b1 derivatives and effective microorganism
ES2772931T3 (en) * 2015-02-05 2020-07-08 Hygienix Bv Procedure to disinfect a surface, and composition suitable for use on it
CN107212236A (en) * 2017-06-26 2017-09-29 苏州凌科特新材料有限公司 A kind of composite biological preservative and preparation method thereof
CN111225564A (en) * 2017-10-16 2020-06-02 株式会社日本抗菌总和研究所 Antibacterial composition
CA3082900A1 (en) * 2017-11-17 2019-05-23 Renovion, Inc. Stable ascorbic acid compositions and methods of using the same
CN108904374A (en) * 2018-07-24 2018-11-30 常州市嘉乐钢板网制造有限公司 Cleaning agent for mouth cavity
KR101976709B1 (en) * 2018-08-08 2019-05-09 주식회사 세니젠 Antimicrobial composition with malic acid, citric acid and phytic acid
CN113995744B (en) * 2021-10-13 2023-03-17 温州肯恩大学 Composition and antibacterial application thereof

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