CN110025607A - Application of the hydroxycitric acid and combinations thereof as preparation prevention and treatment mastitis for milk cows drug - Google Patents

Application of the hydroxycitric acid and combinations thereof as preparation prevention and treatment mastitis for milk cows drug Download PDF

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CN110025607A
CN110025607A CN201810032353.8A CN201810032353A CN110025607A CN 110025607 A CN110025607 A CN 110025607A CN 201810032353 A CN201810032353 A CN 201810032353A CN 110025607 A CN110025607 A CN 110025607A
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acid
hca
drug
milk
hydroxycitric acid
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汪鲲
王巍
曾南方
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Beijing Origin Biotechnology Co Ltd
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Beijing Origin Biotechnology Co Ltd
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/105Aliphatic or alicyclic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/111Aromatic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/116Heterocyclic compounds
    • A23K20/121Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/116Heterocyclic compounds
    • A23K20/132Heterocyclic compounds containing only one nitrogen as hetero atom
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/116Heterocyclic compounds
    • A23K20/137Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/20Inorganic substances, e.g. oligoelements
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/10Feeding-stuffs specially adapted for particular animals for ruminants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/11Aldehydes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/194Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin

Abstract

The present invention provides the new applications that Garcinia Cambogia extract component hydroxycitric acid (HCA) is applied as fungicide or bacteriostatic agent.Hydroxycitric acid (HCA) can inhibit or kill pathogens from dairy cattle affected smastitis.The pathogens from dairy cattle affected smastitis is staphylococcus aureus, Escherichia coli, streptococcus lactis etc..The present invention is with HCA compound collecting composition formula as main component, include: hydroxycitric acid (HCA), citral, Thymol, chlorogenic acid, matrine, cinnamic acid, berberine, scutelloside totally 8 kinds of ingredients in the formula, uses silica as dispersing agent.Product of the present invention for oral use, milk somatic cell number can reduce 30-50% to illness milk cow for three days on end;It is used in conjunction 7 days, milk somatic cell number can reduce 50-80%, and milk somatic cell number can achieve 300,000/ml or so within 1,000,000/ml substantially, meet standard for drinking.It is especially obvious to the serious milk cow control efficiency of some antibiotics resistances.

Description

Application of the hydroxycitric acid and combinations thereof as preparation prevention and treatment mastitis for milk cows drug
Technical field
Application the present invention relates to hydroxycitric acid and combinations thereof as preparation prevention and treatment mastitis for milk cows drug.
Background technique
Mammitis is most common in world's dairy and causes a kind of maximum disease of economic loss, and pathogenic factor is main It is cause pathogeny imcrobe infection.Cause the pathogenic microorganism of mastitis for milk cows sufficiently complex, including bacterium, fungi, virus, mycoplasma Deng more than 130 kinds, wherein (such as staphylococcus aureus, Streptococcusagalactiae, stops newborn hammer at escherichia coli based on bacterium infection Bacterium), followed by fungal infection (such as Candida albicans and Candida tropicalis), and usually from bacterial fungus mixed infection. On the one hand the generation of the disease directly affects the yield and quality of milk, on the other hand can also reduce the service life of milk cow, increase Mortality.Clinically disease incidence is high, prevention and treatment is difficult for the disease, is listed in one of big disease of milk cow four.
Mastitis for milk cows is a kind of inflammation that cow mammary gland is occurred by physical stimulation, chemical stimulation or the invasion of microorganism Disease variation, can cause cow breast tissue damage, fibrosis, reduce the milk yield of milk cow, influence milk quality and nutritive value And the processing of dairy produce, and shorten the milk production time limit of milk cow, it is disease incidence highest in milk cow production, infection is most fast, makes At one of the disease of the largest loss.The disease incidence of clinical type mastitis for milk cows is 30% or so, the morbidity of recessive mastitis for milk cows Rate is up to 50%~70%, and therefore the output of milk of annual milk cow reduces about 15%, and mastitis for milk cows will affect cow producing milk Quality makes milk have the main source of harmful bacteria, causes damages to public health.
Mastitis for milk cows is as caused by a variety of unspecific cause pathogeny imcrobe infections, and wherein 80-90% is by grape ball Bacterium, Escherichia coli and streptococcus cause.The method for treating garget is domestic at present mainly using antibiotic locally injecting method, state It is outer mainly to use vaccine prevention added with antibiotic treatment method.
Due to the difference of home and overseas method for raising dairy cattle, foreign countries concentrate the effect of large-scale cultivation vaccine relatively obvious, Country's dispersion cultivation source of infection is relative complex, and vaccine popularization also needs further to study, and vaccine research is still in exploration at present Stage, expensive, the period is long, and effect is slow, and specificity is strong.And antibiotic or abuse of antibiotics, which is used for a long time, generates receptor very Strong drug resistance, therapeutic effect decline such as take escalated dose that will enter new vicious circle.Residual antibiotic can be right in cow's milk Human body generates very big harm.Long-term drinking dairy products containing antibiotic can make one volume and tire out antibiotic, cause physiologic derangement, make thin Bacterium generates drug resistance to antibiotic, causes difficulty to disease prevention and cure;To antibiotic sensitive subjects, anaphylactic shock also will cause, very To threat to life.In October, 2001, Ministry of Agriculture's publication implements " pollution-free food Fresh Milk " professional standard, to fresh milk Sanitary index specify " antibiotic must not detect ".China has started gradually this stringent professional standard.
American-European countries many years ago i.e. with regulation forbid the antibiotic residue amount of transfiniting milk list it is (residual to penicillin medicine The limitation stayed is ten or so/4ths/10000000ths to ten million).Economic loss how is reduced, cow's milk and cream system how are effectively solved Antibiotic residue problem in product, the world always search for may replace the drug of antibiotic treatment garget.
Currently, there are many treatment means about mastadenitis of cow, as chemical medicinal treatment, recombinant vaccine are treated, carefully Intracellular cytokine treatment, bacterium extract for treating, hormone therapy and the treatment of anti-Pathogenic Bacteria of Dairy Cow Mastitis composite yolk antibody etc..These methods It has his own strong points, though cannot thoroughly cure, certain curative effect can be played.However the side effect of these methods but can not be ignored, it is special It is not medicament residue, jeopardizes human health indirectly.Chinese herbal medicine is natural materials, the effective biotic component containing there are many, is had anti- Bacterium, is not likely to produce the features such as drug resistance at anti-inflammatory, has been that domestic and international expert is of interest using herbal control mastitis for milk cows.
With the continuous improvement of social progress and living standards of the people, people increasingly pay attention to the peace of animal derived food Complete and health.Therefore, the premise up to standard for having become the market access of medicament residue and microorganism detection.Chemical synthetic drug and anti- Generation and serious medicament residue of the raw element due to bacterial drug resistance gradually will be limited the use of and be disabled.It is domestic after China joined WTO Market opens entirely, and the milk product quality in China can not contend with developed country, and the U.S., Mu Deng developed country rely on certainly The scientific and technological advantage of body constructs green trade wall emperor, proposes the test stone being increasingly stringenter to the dairy products for entering this country.Institute Using low toxicity, noresidue, to be not likely to produce the Chinese herbal medicine of bacterial drug resistance and prevent and treat mastitis for milk cows, there is wide application Prospect.
Summary of the invention
The present invention provides the new applications that HCA is applied as fungicide or bacteriostatic agent.HCA can inhibit or kill cow breast Scorching pathogenic bacteria.The pathogens from dairy cattle affected smastitis is staphylococcus aureus, Escherichia coli, streptococcus lactis etc..
The present invention is with HCA compound collecting composition formula as main component, includes: in HCA, citral, hundred in the formula Fragrant phenol, chlorogenic acid, matrine, cinnamic acid, berberine, scutelloside totally 8 kinds of ingredients, use silica as dispersing agent.
Above-mentioned plant extracts is weighed according to certain weight ratio, is uniformly mixed and becomes product of the present invention.
According to an aspect of the invention, there is provided hydroxycitric acid answering as preparation prevention and treatment mastitis for milk cows drug With.
A further aspect according to the present invention, in above-mentioned application mastitis for milk cows by staphylococcus aureus, At least one of Escherichia coli and streptococcus lactis cause.
According to another aspect of the present invention, a kind of product is provided, it is characterised in that it is using hydroxycitric acid as work Property ingredient, and contain other auxiliary materials, wherein the product is the one kind selected from following:
Feed addictive, drinking agent, animal health drug, veterinary drug, drug.
According to a further aspect of the invention, a kind of composition answering as preparation prevention and treatment mastitis for milk cows drug is provided With the weight percent content of each component of the composition are as follows:
Hydroxycitric acid: 30-50,
Citral: 5-10,
Thymol: 5-10,
Chlorogenic acid: 10-20,
Matrine 3-8,
Cinnamic acid 5-10,
Berberine 3-7,
Scutelloside 5-7,
Silica 1 4-20.
A further aspect according to the present invention, in above-mentioned application mastitis for milk cows by staphylococcus aureus, At least one of Escherichia coli and streptococcus lactis cause.
According to a further aspect of the invention, a kind of product is provided, it is characterised in that it is using a kind of composition as work Property ingredient, and contain other auxiliary materials,
Wherein:
The weight percent content of each component of the composition are as follows:
Hydroxycitric acid: 30-50,
Citral: 5-10,
Thymol: 5-10,
Chlorogenic acid: 10-20,
Matrine 3-8,
Cinnamic acid 5-10,
Berberine 3-7,
Scutelloside 5-7,
Silica 1 4-20,
The product is the one kind selected from following:
Feed addictive, drinking agent, animal health drug, veterinary drug, drug.
Detailed description of the invention
Fig. 1 shows that HCA is to staphylococcus aureus inhibition zone in one embodiment of the present of invention, wherein control is that woods can Mycin.Fig. 2 shows that HCA is to streptococcus lactis inhibition zone in one embodiment of the present of invention, wherein control is lincomycin.
Fig. 3 shows that HCA is to escherichia coli inhibition zone in one embodiment of the present of invention, wherein control is lincomycin.
Specific embodiment
Must have an exact restraining and sterilizing bacteria effect using Chinese medicine treatment garget, and with effects of antibiotics and speed phase It is imitative, it is possible to replace antibiotic, this is that a high starting point and numerous researchers are difficult to the difficulty captured for Chinese medicine.
Based on to garget it is pathogenetic understanding and with reference to modern pharmacological research achieve, the present inventor from Garcinia Cambogia, The fruit of a cubeb litsea tree, thyme, honeysuckle, kuh-seng, cortex cinnamomi, the coptis, extract in the natural Chinese medicinal herbs such as radix scutellariae hydroxycitric acid, citral, The effective components such as Thymol, chlorogenic acid, taraxacin, Anemonin, matrine, cinnamic acid, berberine, scutelloside composition 10 The Chinese medical extract of a prevention and treatment mastitis for milk cows is combined into product, these extracts all have good anti-inflammatory, antibacterial, resist and burst Ulcer, activating microcirculation and removing stasis medicinal especially have stronger killing effect to for Staphylococcus aureus, Escherichia coli, salmonella, do not produce The features such as raw drug resistance, quick, drug residue free, milk cow is without dry up's phase.
(HCA (Hydroxy Citric acid, HCA) is a kind of derivative of citric acid to hydroxycitric acid, is widely present In the rainforest plants such as Garcinia Cambogia (Garcinia Cambogia), roselle (Hibiscus Subdariffa).
HCA, chemical structure:
HOOC-CH2-C(OH)(COOH)-CH(OH)-COOH(C6H8O8)。
Garcinia Cambogia originates in India, and such fruit tree of India is referred to as Brindleberry, and scientific name is Garcinia Cambogia.The much like citrus of fruit, is called Luo Wangguo.Garcinia Cambogia be taken as since ancient times the spice of curry powder at point it One.
HCA is derived from natural extract, when human glucose switchs to fat, inhibits wherein ATP- citrate lyase (ATP-Citratelyase), it synthesize fatty acid can not, and inhibit the progress of sugar solution (glycolysis) effect.HCA is logical The synthesis for inhibiting fat to be crossed, promotes the burning of fatty acid, reduces the intake of food, the Trinity has the function that slimming, Be it is a kind of rare, fat-reducing effect is most ideal at present, one of most healthy Weight-reducing health raw material.
When food enters in human body, carbohydrate is decomposed into small molecule glucose, becomes blood glucose into blood, in turn Each cell of whole body is sent to be metabolized as energy.If glucose is not utilized immediately, just it is stored in liver or muscle forms sugar Former (Glycogen), but if glycogen has stored full, glucose is converted to citric acid with citrate cycle through the effect of sugared solution, It catalyzes and synthesizes again through ATP- citrate lyase as fat.HCA contained by Garcinia Cambogia extract is lemon acid-like substance, can be competed Inhibit the activity of ATP- citrate lyase, therefore carbohydrate extra in vivo is hindered to be converted to fatty process, it has been investigated that, In 8-12 hours after meal, HCA can reduce the fatty acid synthesis of 40-70%.
HCA may have the ability for adjusting organism fat metabolism level, therefore HCA becomes part diet products and nutrition One of ingredient of health care product.There is not yet it has the report of sterilization or bacteriostasis efficacy.
First technical problem solved by the invention is to provide the new application of HCA.
Specifically, the present invention provides the new applications that HCA is applied as fungicide or bacteriostatic agent.HCA can inhibit or kill Pathogens from dairy cattle affected smastitis.The pathogens from dairy cattle affected smastitis is staphylococcus aureus, Escherichia coli, streptococcus lactis etc..
The present invention is with HCA compound collecting composition formula as main component, includes: in HCA, citral, hundred in the formula Fragrant phenol, chlorogenic acid, matrine, cinnamic acid, berberine, scutelloside totally 8 kinds of ingredients, use silica as dispersing agent.
Above-mentioned plant extracts is weighed according to certain weight ratio, is uniformly mixed and becomes product of the present invention.
The effective range of extract weight portion rate in its formula are as follows: HCA20-60, citral 5-20, Thymol 5- 20, chlorogenic acid 10-30, matrine 3-20, cinnamic acid 5-30, berberine 3-15, scutelloside 5-15, silica 5-30
Preferably, the composition is composed of the Chinese medical extract of following weight proportion:
HCA30-50, citral 5-10, Thymol 5-10, chlorogenic acid 10-20, matrine 3-10, cinnamic acid 5-15, Huang Even element 3-10, scutelloside 5-10, silica 1 0-20
Extract optimum weight portion rate in the formula are as follows: HCA 30, citral 5, Thymol 5, chlorogenic acid 10, cortex cinnamomi Sour 10, matrine 8, berberine 7, scutelloside 5, silica 20.
In above-mentioned formula, each extract effect is:
1, hydroxycitric acid (Hydroxy Citric acid, HCA) is a kind of derivative of citric acid, is widely present in In the rainforest plants such as Garcinia Cambogia (Garcinia Cambogia), roselle (Hibiscus Subdariffa).HCA chemistry Structure: HOOC-CH2-C (OH) (COOH)-CH (OH)-COOH (C6H8O8).
HCA has the ability for adjusting organism fat metabolism level, therefore HCA becomes part diet products and nutrition and health care One of ingredient of product.The present invention provides the new applications that HCA is applied as fungicide or bacteriostatic agent.HCA can inhibit or kill milk Garget pathogenic bacteria.The pathogens from dairy cattle affected smastitis is staphylococcus aureus, Escherichia coli, streptococcus lactis etc..
2, the molecular formula of citral is C10H16O, is present in lemon-grass oil and litsea citrate oil.
Natural lemon aldehyde is the mixture of two kinds of geometric isomers composition.GB 2760-96 be defined as allowing using it is edible Fragrance.It is mainly used for preparing lemon, citrus and fruit salad type essence, also the primary raw material to synthesize irisone.As tune Pastil prepares lemon extract, also serves as the raw material of synthesis irisone and vitamin A.It is widely used, for needing citris aromas Various aspects.It is lemon type, deodorization die model essence, the important fragrance for manually preparing lemon oil, bergamot oil and petit grain oil.It is Synthesize the raw material of violet ketone, methylionone class.It can also be used to cover the bad breath in industrial production.It can also be used in The edible essences such as ginger, lemon, limette, sweet orange, grapefruit, apple, cherry, grape, strawberry and pungent perfume (or spice).Wine also can be used with essence It.
One aspect of the present invention is to prove it to pathogens from dairy cattle affected smastitis such as Staphylococcus aureus by bacteriostatic test Bacterium, Escherichia coli, streptococcus lactis etc. have significant bacteriostasis.
3, Thymol (Thymol) is a monoterpene, is the amphyl of cymene.Its molecular formula is C10H14O is isomer with carvacrol, gains the name due to being found in thyme.The thymol being obtained by extraction is white Color crystalline solid has pleasant aromatic odor.In perfume industry, it is fragrant to can be used for toothpaste, perfumed soap and certain cosmetics In extract formula, but dosage has certain limitations.Preservative.Pest repellant.
For fragrance processed, drug and indicator etc., it is also commonly used for skin fungus and ringworm.It is also used for baked goods, frost Dairy products, pudding.
4, chlorogenic acid is one of the main antibacterial of honeysuckle, antiviral effective pharmaceutical component.
Chlorogenic acid has wide antibacterial action, but can be inactivated in vivo by protein.It is similar to caffeic acid, take orally or When intraperitoneal injection, the central excitatory of rat can be improved.The small bowel peristalsis of rat and mouse and the tension of rat uterus can be increased. There is choleretic effect, the bile secretion of rat can be promoted.
5, matrine be the dry root leguminous plant kuh-seng, plant, fruit through the organic solvents such as ethyl alcohol extract made of, It is alkaloid.Generally Banlangen, main component have a variety of biologies such as matrine, sophocarpine, N-Oxysophocarpine, Sophoridine Alkali, with matrine, oxymatrine concentration highest.Main function has heat-clearing, diuresis, desinsection, clearing damp and other effects, while also having There are a variety of effects such as antiviral and antitumor antiallergy.
6, cinnamic acid also known as β-cinnamic acid, cinnamic acid.It is to have from what cassia or styrax were isolated Machine acid.The cinnamic acid generated in plant by the degradation of phenylalanine deamination.It is mainly used for flavors and fragrances, food additives, medicine Industry, beauty, pesticide, organic synthesis etc..
7, berberine is a kind of important alkaloid, is the Chinese medical extract of China's application for a long time.Berberine can from the coptis, It is extracted in the plants such as Cortex Phellodendri, barberry.It has significant bacteriostasis.Common Halomine is called Berberine hydrochloride, Berberine can be to resisting pathogenic microbes, to various bacteria such as shigella dysenteriae, tubercle bacillus, pneumococcus, typhoid bacillus and diphtheria Bacillus etc. has inhibiting effect, wherein it is most strong to shigella dysenteriae effect, it is commonly used to the alimentary canals such as treatment bacterial gastroenteritis, dysentery Disease.Clinic is mainly used for treating bacillary dysentery and enterogastritis, its side effect are smaller.
8, scutelloside (baicalin) is from dicotyledonous Lamiaceae plant radix scutellariae (Scutellariabaicalensis Georgi a kind of flavone compound separated is extracted in dry root), is pale yellow powder, bitter under room temperature.Indissoluble It in methanol, ethyl alcohol, acetone, is slightly soluble in chloroform and nitrobenzene, is practically insoluble in water, dissolve in hot acetic acid.It meets ferric trichloride and shows green Color meets lead acetate and generates orange precipitating.It is dissolved in alkali and ammonium hydroxide just displaing yellow, is then become soon dark brown.With significant raw Object activity has antibacterial, diuresis, anti-inflammatory, norcholesterol, antithrombus formation, alleviates asthma, purging fire for removing toxin, hemostasis, miscarriage prevention, resists Allergy and spasmolysis are also the specific inhibitor of mammalian liver sialidase, have the function of adjusting certain diseases, Also there is stronger antitumor response physiological potency.
The advantages of the present invention include:
Fungistatic effect of the present invention to pathogens from dairy cattle affected smastitis such as staphylococcus aureus, Escherichia coli, streptococcus lactis Obviously, bigger than common antibiotics inhibition zone.
The present invention is entirely natural plant extracts, without antibiotics residues;The present invention is 8 kinds of natural plants simultaneously Extract combination formula, various extract Antibacterial Mechanisms are different, so bacterium is not likely to produce drug resistance.
It elaborates with reference to embodiments to the present invention.
Hydroxycitric acid (Hydroxy Citric acid, HCA) is a kind of derivative of citric acid, is widely present in rattan In the rainforest plants such as yellow fruit (Garcinia Cambogia), roselle (Hibiscus Subdariffa).HCA chemistry knot Structure: HOOC-CH2-C (OH) (COOH)-CH (OH)-COOH (C6H8O8).
HCA has the ability for adjusting organism fat metabolism level, therefore HCA becomes part diet products and nutrition and health care One of ingredient of product.The present invention provides the new applications that HCA is applied as fungicide or bacteriostatic agent.HCA can inhibit or kill milk Garget pathogenic bacteria.The pathogens from dairy cattle affected smastitis is staphylococcus aureus, Escherichia coli, streptococcus lactis etc..
Embodiment 1:HCA is to staphylococcus aureus extracorporeal bacteria inhibitor test
Sample source: gamboge berry extract HCA (60%) is provided by Beijing Sunplant Biological Technology Co., Ltd.;Antibacterial reality Testing and selecting two plants of Escherichia coli, two plants of staphylococcus aureuses and one plant of streptococcus uberis is standard bacteria.
2, material and instrument
Rubber head dropper, tweezers, Oxford cup, pipette (2ml, 5ml, 20ml), culture dish, conical flask, nutrient agar culture Base, beaker, distilled water, water-bath, thermometer, alcohol swab.3, prepare
(1), it sterilizes: dropper, tweezers, Oxford cup, pipette (2ml, 5ml, 20ml), culture dish, beaker is dry at 160 DEG C Heat sterilization 3 hours, configured culture medium and 50ml distilled water are used for high pressure steam sterilization 20 minutes at 121 DEG C for test.
(2), sample treatment: sample label it is unmarked with water dissolution (note: the character of sample, dissolved state with And final test concentration used is seen attached list)
(3), reference substance solution selects: water dissolution sample using 10% lincomycin injection dilute 10 times as pair According to product solution;
4, staphylococcus aureus inhibition zone test step
(1), culture dish (sample ID, solubilising reagent, concentration, reference substance) is marked
(2), the staphylococcus aureus on inclined-plane is washed in 50ml sterile water with about 2ml is sterile, mixes, takes about 8ml bacterium solution is put into 400ml culture dish, is mixed, and culture is based on keeping the temperature in 45 DEG C of water-baths.
(3), the culture medium after taking 20ml to add bacterium solution with macropore pipette is added separately in each culture dish, is shaken up, quiet It sets complete to solidification.
(4), 3 holes, the hole of respectively two sample wells and 1 reference substance solution are made a call on each ware with Oxford cup.
(5), the sample solution and reference substance solution of corresponding concentration, generally 1-2 drop are separately added into hole, paying attention to cannot Solution cannot overflow.
(6), culture dish is put down to take to lay flat to be placed in 37 DEG C of constant incubators to cultivate 17 hours and observes result later.
(7), the culture dish of inhibition zone takes pictures growth, in order to carry out the summary and analysis of test result.
Note: the inhibition zone examination of the inhibition zone test step and staphylococcus aureus of subsequent Escherichia coli and streptococcus lactis Test that step is similar, the incubation time of three kinds of bacterium is about 17 hours.
5, bacteriostatic test result
Fig. 1 is the HCA of embodiment 1 to staphylococcus aureus inhibition zone, wherein control is lincomycin, H17 is HCA sample Product tested number: what label " 0.6 " was indicated is the inhibition zone that sample quality is 0.6 gram;What label " 1.0 " was indicated is that sample quality is 1.0 grams of inhibition zone, what label " 0 " was indicated is the inhibition zone of lincomycin;Concrete outcome is as listed in table 2.
Character after table 1, HCA sample property and dissolution
Embodiment 2:HCA is to streptococcus lactis extracorporeal bacteria inhibitor test
Streptococcus lactis inhibition zone test step
(1), culture dish (sample ID, solubilising reagent, concentration, reference substance) is marked
(2), the streptococcus lactis on inclined-plane is washed in 50ml sterile water with about 2ml is sterile, mixes, takes about 8ml bacterium solution It is put into 400ml culture dish, mixes, culture is based on keeping the temperature in 45 DEG C of water-baths.
(3), the culture medium after taking 20ml to add bacterium solution with macropore pipette is added separately in each culture dish, is shaken up, quiet It sets complete to solidification.
(4), 3 holes, the hole of respectively two sample wells and 1 reference substance solution are made a call on each ware with Oxford cup.
(5), it is separately added into the HCA sample solution and reference substance solution of corresponding concentration, generally 1-2 drop in hole, pays attention to Being unable to solution cannot overflow.
(6), culture dish is put down to take to lay flat to be placed in 37 DEG C of constant incubators to cultivate 17 hours and observes result later.
(7), the culture dish of inhibition zone takes pictures growth, in order to carry out the summary and analysis of test result.
Character is the same as table 1 after the sample property of HCA and dissolution.
Fig. 2 is the HCA of embodiment 2 to streptococcus lactis inhibition zone, wherein control is lincomycin, H17 is HCA sampling test Number: what label " 0.6 " was indicated is the inhibition zone that sample quality is 0.6 gram;What label " 1.0 " was indicated is that sample quality is 1.0 grams Inhibition zone, label " 0 " indicate is lincomycin inhibition zone;Concrete outcome is as listed in table 2.
Embodiment 3:HCA is to Escherichia coli extracorporeal bacteria inhibitor test
Escherichia coli inhibition zone test procedure
(1), culture dish (sample ID, solubilising reagent, concentration, reference substance) is marked
(2), the Escherichia coli on inclined-plane are washed in 50ml sterile water with about 2ml is sterile, mix, takes about 8ml bacterium solution It is put into 400ml culture dish, mixes, culture is based on keeping the temperature in 45 DEG C of water-baths.
(3), the culture medium after taking 20ml to add bacterium solution with macropore pipette is added separately in each culture dish, is shaken up, quiet It sets complete to solidification.
(4), 3 holes, the hole of respectively two sample wells and 1 reference substance solution are made a call on each ware with Oxford cup.
(5), it is separately added into the HCA sample solution and reference substance solution of corresponding concentration, generally 1-2 drop in hole, pays attention to Being unable to solution cannot overflow.
(6), culture dish is put down to take to lay flat to be placed in 37 DEG C of constant incubators to cultivate 17 hours and observes result later.
(7), the culture dish of inhibition zone takes pictures growth, in order to carry out the summary and analysis of test result.
Character is the same as table 1 after HCA sample property and different solvents dissolution.
Fig. 3 is the HCA of embodiment 3 to escherichia coli inhibition zone, wherein control is lincomycin, H17 is HCA sampling test Number: what label " 0.6 " was indicated is the inhibition zone that sample quality is 0.6 gram;What label " 1.0 " was indicated is that sample quality is 1.0 grams Inhibition zone, label " 0 " indicate is lincomycin inhibition zone;Concrete outcome is as listed in table 2.
Table 2HCA bacteriostatic test result
It is to have fungistatic effect that note * antibacterial circle diameter, which is greater than 10mm, and it is significant fungistatic effect that antibacterial circle diameter, which is greater than 20mm,.
In terms of In Vitro Bacteriostasis circle test effect, HCA has significant fungistatic effect to staphylococcus aureus, streptococcus lactis, It to the fungistatic effect that Escherichia coli also have, but is not apparent.
Embodiment 1-3 bacteriostatic test shows that HCA is obvious to staphylococcus aureus, streptococcus lactis fungistatic effect, but to big Enterobacteria fungistatic effect is unobvious,
Suppression of the composite formula of embodiment 4:HCA and other Chinese medical extracts to staphylococcus aureus and Escherichia coli Bacterium effect
Formula 1: related substances are accurately weighed as following weight percent: HCA 30, citral 5, Thymol 5, green original Sour 10, cinnamic acid 10, matrine 8, berberine 7, scutelloside 5, silica 20.Total 100 parts, each raw material is uniformly mixed it is For formula 1.
Formula 2: related substances are accurately weighed as following weight percent: HCA50, citral 5, Thymol 5, chlorogenic acid 10, matrine 3, cinnamic acid 5, berberine 3, scutelloside 5, silica 14.Total 100 parts, each raw material is uniformly mixed it is Formula 2.
Formula 3: related substances are accurately weighed as following weight percent: formula components: HCA40, citral 5, thyme Phenol 10, chlorogenic acid 10, matrine 5, cinnamic acid 5, berberine 3, scutelloside 7, silica 15.It is 100 parts total, each raw material is equal Even mixing is formula 3.
1, material and instrument
Rubber head dropper, tweezers, Oxford cup, pipette (2ml, 20ml), culture dish, conical flask, disposable glove, agar battalion Support culture medium, beaker, distilled water, water-bath, thermometer, alcohol swab, waste liquid cylinder, dimethyl sulfoxide
2, the preparation before testing
(1), above-mentioned material and instrument are ready to
2, culture medium (preparing according to 20ml is put in each culture dish) is prepared, after preparing, first added on electromagnetic oven To being completely dissolved and (be heated to micro-boiling).
(3), rubber head dropper, tweezers, Oxford cup, pipette (2ml, 20ml), culture dish, beaker xeothermic are gone out at 160 DEG C Bacterium 3 hours, configured culture medium and 2 50ml distilled water are used for high pressure steam sterilization 20 minutes at 121 DEG C for test.
(4), 1 sample for the treatment of formulations: according to the solvent sample dissolution indicated, the dissolution of powdered samples water is made The solution of 0.5g/2ml, 1.0g/2ml.
(5), prepare reference substance solution: taking 10% lincomycin injection to dilute 10 times and used as reference substance solution.
3, inhibition zone test step
(1), culture dish (sample ID, solubilising reagent, concentration, reference substance) is marked
(2), sterile inclined-plane of the washing with Escherichia coli, staphylococcus aureus about 2ml is used respectively, and the bacterium after washing Liquid pours into 50ml sterile water, mixes, about 10ml bacterium solution is taken to be put into culture dish, mixes, and culture dish is put in 45 DEG C of water-baths Keep constant temperature.
(3), the culture medium after taking 20ml to add bacterium solution with macropore pipette is added separately in each culture dish, is shaken up, quiet It sets complete to solidification.
(4), the markd place punching on culture medium with the Oxford cup after sterilizing, and the culture medium in hole is taken out It discards.
(5), the sample solution and reference substance solution of corresponding concentration, generally 1-2 drop are separately added into hole, paying attention to cannot Solution cannot overflow.
(6), culture dish is put down to take to lay flat to be placed in 37 DEG C of constant incubators to cultivate 17 hours and observes result later.
(7), the culture dish of inhibition zone takes pictures growth, in order to carry out the summary and analysis of test result.
Tri- kinds of table 3, HCA combination formula bacteriostatic test results
It is to have fungistatic effect that note * antibacterial circle diameter, which is greater than 10mm, and it is significant fungistatic effect that antibacterial circle diameter, which is greater than 20mm,.
As can be seen from Table 3, three kinds of combination formulas of HCA significantly increase Escherichia coli bacteriostasis, antibacterial circle diameter Above 30mm, to staphylococcus aureus bacteriostatic diameter also than also increasing for HCA antibacterial circle diameter is used alone.
Control efficiency milk somatic cell number of the composition of embodiment 5:HCA and other Chinese medical extracts to mastitis for milk cows (somatic cell count, SCC) refers to the total number of cells in every milliliter of milk, and majority is leucocyte, usually thin by macrophage The composition such as born of the same parents, lymphocyte, polymorph neutrophile leucocytes and a small amount of breast tissue epithelial cell, accounts for about bovine somatic cells number 95%, remaining is that breast tissue is die the epithelial cell to fall off.Somatic number reflects the health status of milk quality and milk cow, Under normal circumstances, in milk somatic number generally in 20,000~300,000/ml.
Test procedure: related substances are accurately weighed as following weight percent: HCA 30, citral 5, Thymol 5, green Ortho acid 10, cinnamic acid 10, matrine 8, berberine 7, scutelloside 5, silica 20 amount to 100 parts, will be weighed each above-mentioned Material mixing is uniform, is as formulated 1.1 product 30g of formula is uniformly mixed with cow concentrate, feeding in continuous 7 days suffers from mammitis Milk cow, acquire each illness breast institute lactation liquid of every ox daily, controlled respectively with California mammitis detection method (CMT) qualitative analysis Whether the somatic number of infected cattle lactation substantially reduces after treatment.Illness after preceding and treatment is treated in quantitative determination respectively on the basis of the above The somatic number of milk cow institute lactation, the results are shown in Table 4.
Table 4: 1 formula of formula is to mastitis for milk cows therapeutic effect
The test result of table 4 shows: passing through 3 days 1 products of inventive formulation for oral use, milk somatic cell number can reduce 30-50%;By 7 days oral origin health, milk somatic cell number can reduce 50-80%, and milk somatic cell number is in 1,000,000/ml Within can achieve 300,000/ml or so substantially, meet standard for drinking.Especially the serious milk cow of some antibiotics resistances is prevented and treated Effect is obvious.
Example of the invention is described in detail above, but the content is only preferred embodiments of the invention, it cannot It is believed to be used to limit the scope of the invention.Any changes and modifications in accordance with the scope of the present application, should all It falls within the scope of the patent of the present invention.

Claims (8)

1. application of the hydroxycitric acid as preparation prevention and treatment mastitis for milk cows drug.
2. application according to claim 1, wherein mastitis for milk cows is by staphylococcus aureus, Escherichia coli and newborn hammer At least one of bacterium causes.
3. a kind of product, it is characterised in that it contains other auxiliary materials using hydroxycitric acid as active constituent, wherein the production Product are the one kind selected from following:
Feed addictive,
Drinking agent,
Animal health drug,
Veterinary drug,
Drug.
4. a kind of application of composition as preparation prevention and treatment mastitis for milk cows drug, the weight percent of each component of the composition Compare content are as follows:
Hydroxycitric acid: 30-50,
Citral: 5-10,
Thymol: 5-10,
Chlorogenic acid: 10-20,
Matrine 3-8,
Cinnamic acid 5-10,
Berberine 3-7,
Scutelloside 5-7,
Silica 1 4-20.
5. application according to claim 4, wherein mastitis for milk cows by staphylococcus aureus and streptococcus lactis extremely Few one kind causes.
6. application according to claim 4 or 5, wherein the weight percent content of each component of the composition are as follows:
Hydroxycitric acid: 30,
Citral: 5,
Thymol: 5,
Chlorogenic acid: 10,
Cinnamic acid 10,
Matrine: 8,
Berberine: 7,
Scutelloside: 5,
Silica: 20.
7. a kind of product, it is characterised in that it contains other auxiliary materials using a kind of composition as active constituent,
Wherein:
The weight percent content of each component of the composition are as follows:
Hydroxycitric acid: 30-50,
Citral: 5-10,
Thymol: 5-10,
Chlorogenic acid: 10-20,
Matrine 3-8,
Cinnamic acid 5-10,
Berberine 3-7,
Scutelloside 5-7,
Silica 1 4-20,
The product is the one kind selected from following:
Feed addictive, drinking agent, animal health drug, veterinary drug, drug.
8. product according to claim 7, wherein the weight percent content of each component of the composition are as follows:
Hydroxycitric acid: 30,
Citral: 5,
Thymol: 5,
Chlorogenic acid: 10,
Cinnamic acid 10,
Matrine: 8,
Berberine: 7,
Scutelloside: 5,
Silica: 20.
CN201810032353.8A 2018-01-12 2018-01-12 Application of the hydroxycitric acid and combinations thereof as preparation prevention and treatment mastitis for milk cows drug Pending CN110025607A (en)

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CN115475156A (en) * 2022-09-15 2022-12-16 广州医科大学附属第一医院(广州呼吸中心) Application of hydroxycitric acid in preparation of drug for preventing and treating Landel's spots

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