CN110772526A - Neomycin sulfate solution and preparation method thereof - Google Patents
Neomycin sulfate solution and preparation method thereof Download PDFInfo
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- CN110772526A CN110772526A CN201910967796.0A CN201910967796A CN110772526A CN 110772526 A CN110772526 A CN 110772526A CN 201910967796 A CN201910967796 A CN 201910967796A CN 110772526 A CN110772526 A CN 110772526A
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- neomycin sulfate
- solution
- sulfate solution
- berberine hydrochloride
- neomycin
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- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 title claims abstract description 96
- 229940053050 neomycin sulfate Drugs 0.000 title claims abstract description 96
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 44
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 claims abstract description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 16
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 15
- 229960000583 acetic acid Drugs 0.000 claims abstract description 9
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 9
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims abstract description 9
- 235000010234 sodium benzoate Nutrition 0.000 claims abstract description 9
- 239000004299 sodium benzoate Substances 0.000 claims abstract description 9
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 8
- 239000001103 potassium chloride Substances 0.000 claims abstract description 8
- 239000011780 sodium chloride Substances 0.000 claims abstract description 8
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 6
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 102
- 239000011259 mixed solution Substances 0.000 claims description 29
- 238000002156 mixing Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 244000144977 poultry Species 0.000 claims description 8
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 8
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 8
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 235000002639 sodium chloride Nutrition 0.000 claims description 7
- 235000006708 antioxidants Nutrition 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 229960004499 scopolamine hydrobromide Drugs 0.000 claims description 4
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 claims description 4
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 244000144972 livestock Species 0.000 claims description 2
- 238000010979 pH adjustment Methods 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 229940001474 sodium thiosulfate Drugs 0.000 claims description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 16
- 239000003651 drinking water Substances 0.000 abstract description 7
- 235000020188 drinking water Nutrition 0.000 abstract description 7
- CXYRUNPLKGGUJF-RAFJPFSSSA-M scopolamine methobromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 CXYRUNPLKGGUJF-RAFJPFSSSA-M 0.000 abstract description 3
- 206010022998 Irritability Diseases 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract 1
- 239000008213 purified water Substances 0.000 description 26
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 16
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 16
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 16
- 229960002646 scopolamine Drugs 0.000 description 16
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 16
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 15
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 15
- 241000287828 Gallus gallus Species 0.000 description 12
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- 241000894006 Bacteria Species 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
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- 210000001124 body fluid Anatomy 0.000 description 2
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- 238000009395 breeding Methods 0.000 description 2
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- 230000006378 damage Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000000273 veterinary drug Substances 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000000816 effect on animals Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- OCATYIAKPYKMPG-UHFFFAOYSA-M potassium bromate Chemical compound [K+].[O-]Br(=O)=O OCATYIAKPYKMPG-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
Classifications
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/4353—Heterocyclic 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
- A61K31/4375—Heterocyclic 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
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- General Health & Medical Sciences (AREA)
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Abstract
The invention belongs to the technical field of veterinary medicine, and discloses a neomycin sulfate solution which comprises the following components in parts by weight: neomycin sulfate 300-500 g/L; 2-15g/L of potassium chloride; 2-15g/L of sodium chloride; 0.1-2g/L berberine hydrochloride; 0.5-5g/L of scopolamine methobromide; 0.1-2g/L of antioxidant; 2-8g/L of sodium benzoate; glacial acetic acid 5-20 g/L; the solvent is water. The neomycin sulfate solution has high uniformity, high stability, drinking water administration, low labor intensity and low irritability; and the preparation process is simple, the operation is convenient, and the industrialization is easy to realize.
Description
Technical Field
The invention belongs to the technical field of veterinary medicine, and particularly relates to a high-efficiency neomycin sulfate solution and a preparation method thereof.
Background
Neomycin sulfate is a common veterinary drug at home and abroad, and has good antibacterial effect on bacteria in enterobacteriaceae such as staphylococcus (methicillin sensitive strain), corynebacterium, escherichia coli, klebsiella, proteus and the like as a second clinically applied aminoglycoside antibiotic. Neomycin sulfate pharmacokinetics shows that oral administration is rarely absorbed (about 3%), interferes with the synthesis of bacterial proteins by acting on ribosomes associated with bacterial cell membranes, kills them by only short contact with bacteria, and is largely unchanged after oral administration and excreted in feces. Therefore, the medicament has no residue in vivo and no toxic or side effect on animals, and is a very safe oral medicament.
Neomycin sulfate solution is mainly a special medicine for gastrointestinal tract infection caused by gram-negative bacteria of poultry, and neomycin sulfate pharmacokinetics shows that although the neomycin sulfate is rarely absorbed (about 3 percent) by oral administration, a large dosage is taken for a long time, the neomycin sulfate can still be absorbed by intestinal mucosa with ulcer or inflammation, and particularly, the blood concentration can be obviously increased when the renal function is reduced. Neomycin has nephrotoxicity, ototoxicity and neuromuscular blocking effects.
At present, most of farmers cannot control the administration time and the administration amount under the condition of not quickly feeding back the curative effect of neomycin sulfate, and a large amount of neomycin sulfate solution is used for poultry for a long time. In order to reduce the ecological harm of unnecessary damage and overuse to animals, the development of a neomycin sulfate solution with high efficiency and low toxicity is necessary, and the development of the poultry breeding industry is better promoted.
Disclosure of Invention
The invention aims to provide a neomycin sulfate solution and a preparation method thereof.
In order to achieve the purpose, the invention adopts the technical scheme that:
a neomycin sulfate solution is composed of the following components:
preferably, the neomycin sulfate solution consists of the following components:
preferably, the berberine hydrochloride is recrystallized berberine hydrochloride, and is prepared by the following method: placing methanol in a constant-temperature water bath at 60-65 ℃, adding berberine hydrochloride into the constant-temperature water bath until the methanol is saturated, raising the temperature of the water bath to 68-72 ℃, preserving the heat for 1-1.5h, separating out berberine hydrochloride, and filtering to obtain recrystallized berberine hydrochloride.
Because the berberine hydrochloride has low solubility in water, the berberine hydrochloride with certain solubility is required in the invention, and the berberine hydrochloride after recrystallization can increase the solubility in water, and can generate synergistic action with scopolamine methobromide which is soluble in water, thereby improving the antibacterial action of the neomycin sulfate solution.
Preferably, the antioxidant is selected from one or more of sodium metabisulfite, sodium thiosulfate and ascorbic acid.
A preparation method of neomycin sulfate solution comprises the following steps:
1) respectively preparing a neomycin sulfate solution and a scopolamine hydrobromide solution, and mixing the neomycin sulfate solution and the scopolamine hydrobromide solution to obtain a mixed solution A;
2) preparing berberine hydrochloride solution;
3) dissolving an antioxidant, sodium benzoate, potassium chloride and sodium chloride in water to obtain a mixed solution B;
4) and uniformly mixing the mixed solution A, the berberine hydrochloride solution and the mixed solution B, and adding glacial acetic acid to adjust the pH value to obtain the neomycin sulfate solution.
Preferably, the stirring time of step 4) is 5-10 min.
Preferably, the pH adjustment in step 4) is to adjust the pH to 5-6.
An antibacterial medicine for livestock and poultry comprises the neomycin sulfate solution.
The beneficial technical effects of the invention are as follows:
the neomycin sulfate solution has high uniformity, high stability, drinking water administration, low labor intensity and low irritability; and the preparation process is simple, the operation is convenient, and the industrialization is easy to realize.
1) The neomycin sulfate solution of the invention is added with a proper amount of scopolamine methobromide and berberine hydrochloride, which have synergistic effect, thereby not only shortening the treatment time of the diarrhea caused by poultry bacterial infection, but also improving the cure rate; and the two can reduce the dosage by cooperating with each other, reduce the generation of antibiotic resistant bacteria, and is beneficial to the healthy and long-term development of poultry breeding industry.
2) The neomycin sulfate solution uses cheap, easily-obtained, nontoxic and safe purified water, and the used antioxidant and preservative are recognized nontoxic medicines and food additives, so that the stability of the neomycin sulfate solution is ensured.
3) The neomycin sulfate solution is added with a proper amount of inorganic salt ions, namely potassium ions and sodium ions, so that body fluid after diarrhea of the poultry can be quickly supplemented, and a series of severe physical energy consumption caused by excessive loss of body fluid due to diarrhea is reduced.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail by examples below. It should be understood, however, that the description herein of specific embodiments is only intended to illustrate the invention and not to limit the scope of the invention.
Example 1
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate with 600L of purified water to obtain neomycin sulfate solution, dissolving scopolamine bromate with 30L of purified water to obtain scopolamine bromate solution, and mixing the neomycin sulfate solution and the scopolamine bromate solution to obtain mixed solution A;
2) dissolving recrystallized berberine hydrochloride in 50L purified water to obtain berberine hydrochloride solution;
3) dissolving sodium metabisulfite, sodium benzoate, potassium chloride and sodium chloride in 10L of purified water to obtain a mixed solution B;
4) mixing the mixed solution A, the berberine hydrochloride solution and the mixed solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the residual purified water to obtain the neomycin sulfate solution.
Example 2
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate with 600L of purified water to obtain neomycin sulfate solution, dissolving scopolamine bromate with 30L of purified water to obtain scopolamine bromate solution, and mixing the neomycin sulfate solution and the scopolamine bromate solution to obtain mixed solution A;
2) dissolving recrystallized berberine hydrochloride in 50L purified water to obtain berberine hydrochloride solution;
3) dissolving sodium metabisulfite, sodium benzoate, potassium chloride and sodium chloride in 10L of purified water to obtain a mixed solution B;
4) mixing the mixed solution A, the berberine hydrochloride solution and the mixed solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the residual purified water to obtain the neomycin sulfate solution.
Example 3
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate with 600L of purified water to obtain neomycin sulfate solution, dissolving scopolamine bromate with 30L of purified water to obtain scopolamine bromate solution, and mixing the neomycin sulfate solution and the scopolamine bromate solution to obtain mixed solution A;
2) dissolving recrystallized berberine hydrochloride in 50L purified water to obtain berberine hydrochloride solution;
3) dissolving sodium metabisulfite, sodium benzoate, potassium chloride and sodium chloride in 10L of purified water to obtain a mixed solution B;
4) mixing the mixed solution A, the berberine hydrochloride solution and the mixed solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the residual purified water to obtain the neomycin sulfate solution.
Comparative example 1
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate in 60L of purified water to obtain neomycin sulfate solution;
2) dissolving sodium metabisulfite and sodium benzoate in 2L of purified water to obtain a mixed solution B;
3) and mixing the neomycin sulfate solution with the solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the rest water to obtain the neomycin sulfate solution.
Comparative example 2
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate with 60L of purified water to obtain neomycin sulfate solution, dissolving scopolamine bromate with 10L of purified water to obtain scopolamine bromate solution, and mixing the neomycin sulfate solution and the scopolamine bromate solution to obtain mixed solution A;
2) dissolving sodium metabisulfite and sodium benzoate in 2L of purified water to obtain a mixed solution B;
3) and mixing the mixed solution A and the mixed solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the residual purified water to obtain the neomycin sulfate solution.
Comparative example 3
A neomycin sulfate solution is composed of the following components:
a preparation method of neomycin sulfate solution comprises the following steps:
1) dissolving neomycin sulfate with 60L of purified water to obtain neomycin sulfate solution, dissolving scopolamine bromate with 10L of purified water to obtain scopolamine bromate solution, and mixing the neomycin sulfate solution and the scopolamine bromate solution to obtain mixed solution A;
2) dissolving sodium metabisulfite, sodium benzoate, potassium chloride and sodium chloride in 10L of purified water to obtain a mixed solution B;
3) and mixing the mixed solution A and the mixed solution B, stirring for 5 minutes, adding glacial acetic acid to adjust the pH value to 5.5, and finally adding the residual purified water to obtain the neomycin sulfate solution.
Test example 1: stability testing of neomycin sulfate solutions
1 purpose of the test: the stability of the neomycin sulfate solution provided by the invention is verified by detecting relevant indexes of the neomycin sulfate solution.
2 test drugs: neomycin sulfate solutions (prepared as in examples 1, 2, 3, respectively); all the raw materials and finished products are commercial products.
3 test method
① Properties by visual inspection, the color and morphology of the sample were observed.
② clarity degree by visual inspection, according to the appendix of the first edition of the pharmacopoeia of the people's republic of China 2015 (appendix 0902).
③ content, and determining the content of neomycin sulfate by referring to neomycin sulfate solution determination method on page 296 of 2017 edition chemical product volume of veterinary quality Standard.
4, test results:
the content, the properties and the clarity of the neomycin sulfate solution prepared by the method are inspected, and the neomycin sulfate content is determined by referring to a neomycin sulfate solution determination method on page 296 of a chemical product volume of 2017 edition of veterinary drug quality standards; the results show that: the neomycin sulfate solution (inventive examples 1, 2, 3) still meets the specifications after 24 months of long-term testing. The stability results of the neomycin sulfate solution for long term testing are shown in Table 1.
TABLE 1
Test example 2: investigation of curative effect of different drug combinations on adult naturally sick chickens
1 purpose of the test: the synergistic effect of the compatible medicines of the neomycin sulfate solution is verified by detecting the treatment effect of the neomycin sulfate solution provided by the invention.
2 test drugs: test products: neomycin sulfate solutions (prepared according to examples 1, 2 and comparative examples 1, 2, 3, respectively); all the raw materials and finished products are commercial products.
3, test method: 360 naturally sick diarrhea-diarrhea broiler chickens are selected, the weight of the broiler chickens is about 1g/L, the broiler chickens are randomly divided into 6 groups, and each group comprises 60 broiler chickens.
Group A was a blank control group, no drug treatment was given, and 5 days were observed.
Group B was treated with the neomycin sulfate solution of example 1 by the method: drinking water, 0.4ml for each 1L water, 2 times a day, and 3 days continuously.
Group C was treated with the neomycin sulfate solution of example 2, using the following method: drinking water, 0.4ml for each 1L water, 2 times a day, and 3 days continuously.
Group D was treated with the neomycin sulfate solution of comparative example 1, using the following method: drinking water, 0.4ml for each 1L water, 2 times a day, and 5 days continuously.
Group E was treated with the neomycin sulfate solution of comparative example 2, using the following method: drinking water, 0.4ml for each 1L water, 2 times a day, and 5 days continuously.
Group F was treated with the neomycin sulfate solution of comparative example 3, using the following method: drinking water, 0.4ml for each 1L water, 2 times a day, and 5 days continuously.
After the treatment is started, the change of the body state of the sick chicken and the death condition of the chicken are recorded daily, and the treatment effect is counted after 5 days of treatment, wherein:
and (4) invalidation: the symptoms of the sick chicken are not obviously improved and even worsen to death.
The method has the following advantages: the symptoms of the sick chicken are obviously improved compared with the symptoms before the medicine is taken.
And (3) curing: the symptoms of the sick chicken disappear after the treatment course is finished, the body is recovered to be healthy, and the sick chicken does not relapse within 2 days.
The curative effect is judged to be good, and diarrhea is basically stopped after the medicine is taken for one day. The curative effect is 'excellent', the diarrhea is obviously improved after the medicine is taken for two days, the curative effect is 'good', the diarrhea is improved after the medicine is taken for 4 days, and the curative effect is 'poor'.
And 4, conclusion: the data analysis in the following table shows that the treatment effect of the chicken with diarrhea and diarrhea of the embodiments 1 and 2 is obvious, the treatment course is short, and the treatment advantages are obvious. The comparative examples 2 and 3 used as a comparison also had better efficacy and treatment rate than the simple neomycin sulfate of comparative example 1; the comparison shows that the berberine hydrochloride, scopolamine bromate, potassium chloride and sodium chloride added into the neomycin sulfate solution play an irreplaceable role in promoting the treatment course and improving the curative effect. The addition amount of berberine hydrochloride is almost the same as the concentration curative effect of 2g/L/1000L when the addition amount of berberine hydrochloride is 1g/L/1000L, so the most suitable addition amount of berberine hydrochloride is not more than 1 g/L/1000L.
TABLE 2 therapeutic effect of different drugs for neomycin sulfate
Claims (8)
1. The neomycin sulfate solution is characterized by consisting of the following components:
2. the neomycin sulfate solution of claim 1, consisting of:
3. the neomycin sulfate solution of claim 1 or 2, wherein the berberine hydrochloride is recrystallized berberine hydrochloride, prepared by the following method: placing methanol in a constant-temperature water bath at 60-65 ℃, adding berberine hydrochloride into the constant-temperature water bath until the methanol is saturated, raising the temperature of the water bath to 68-72 ℃, preserving the heat for 1-1.5h, separating out berberine hydrochloride, and filtering to obtain recrystallized berberine hydrochloride.
4. The neomycin sulfate solution of claim 1 or 2, wherein the antioxidant is selected from one or more of sodium metabisulfite, sodium thiosulfate and ascorbic acid.
5. The process for the preparation of a neomycin sulfate solution according to any one of claims 1 to 4, characterized in that it comprises the following steps:
1) respectively preparing a neomycin sulfate solution and a scopolamine hydrobromide solution, and mixing the neomycin sulfate solution and the scopolamine hydrobromide solution to obtain a mixed solution A;
2) preparing berberine hydrochloride solution;
3) dissolving an antioxidant, sodium benzoate, potassium chloride and sodium chloride in water to obtain a mixed solution B;
4) and uniformly mixing the mixed solution A, the berberine hydrochloride solution and the mixed solution B, and adding glacial acetic acid to adjust the pH value to obtain the neomycin sulfate solution.
6. The method according to claim 5, wherein the stirring time in the step 4) is 5 to 10 min.
7. The method according to claim 5, wherein the pH adjustment in step 4) is performed by adjusting the pH to 5 to 6.
8. An antibacterial agent for livestock and poultry, characterized by comprising the neomycin sulfate solution according to any one of claims 1 to 4.
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