CN116806838A - Liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and preparation methods and applications thereof - Google Patents
Liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and preparation methods and applications thereof Download PDFInfo
- Publication number
- CN116806838A CN116806838A CN202310743489.0A CN202310743489A CN116806838A CN 116806838 A CN116806838 A CN 116806838A CN 202310743489 A CN202310743489 A CN 202310743489A CN 116806838 A CN116806838 A CN 116806838A
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- CN
- China
- Prior art keywords
- liquid preparation
- mass fraction
- fluoro
- methoxyphenyl
- amine
- Prior art date
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- Pending
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- 239000007788 liquid Substances 0.000 title claims abstract description 420
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- 239000006184 cosolvent Substances 0.000 claims abstract description 108
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- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 claims description 130
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- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
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- AXPCHVXFDHPTBW-UHFFFAOYSA-N n-(3-methoxyphenyl)-7h-purin-6-amine Chemical compound COC1=CC=CC(NC=2C=3NC=NC=3N=CN=2)=C1 AXPCHVXFDHPTBW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
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- 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
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/02—Acyclic compounds
-
- 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
- A01N37/12—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 the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
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- 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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/12—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings condensed with a carbocyclic ring
-
- 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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/22—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom rings with more than six members
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- A01N45/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds having three or more carbocyclic rings condensed among themselves, at least one ring not being a six-membered ring
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- A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
- A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
- A01N57/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing acyclic or cycloaliphatic radicals
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- 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
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Abstract
Description
技术领域Technical field
本发明涉及含2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂及其制备方法和应用,属于农业化学品技术领域。The invention relates to a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine and its preparation method and application, and belongs to the technical field of agricultural chemicals.
背景技术Background technique
根据中国农药工业协会报道,2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)是ISO新公布的一种含氟嘌呤类细胞分裂素,其化学文摘社登录号为1089014-47-0;国际通用名称为anisiflupurin(P);中文化学名称为2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺;分子式为C12H10FN5O;相对分子质量为259.239;熔点为195℃;是一种6-苯胺基嘌呤衍生物;其化学结构如下:According to the China Pesticide Industry Association, 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine (Anisiflupurin) is a newly announced fluorine-containing purine cytokinin by ISO. Its chemical The abstract registration number is 1089014-47-0; the international common name is anisiflupurin (P); the Chinese scientific name is 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine; the molecular formula is C 12 H 10 FN 5 O; relative molecular mass is 259.239; melting point is 195°C; it is a 6-anilinopurine derivative; its chemical structure is as follows:
Anisiflupurin原药为白色结晶粉末,难溶于水,微溶于乙醇,在酸、碱中稳定。Anisiflupurin是一种6-苯胺基嘌呤衍生物;在农业方面,具有可刺激烟草愈伤组织生长、保持离体小麦叶片中叶绿素含量的作用,也可诱导苋菜子叶中β-花青素的合成,对由非生物胁迫诱导的细胞分裂素氧化/脱氢酶起抑制作用。且离体试验结果表明,anisiflupurin具有较低的毒性,对哺乳动物骨肉瘤细胞系HOS、乳腺癌细胞系MCF-7和小鼠细胞系成纤维细胞NIH-3T3等细胞的毒性与激动素(kinetin)的毒性相当,80次传代后比激动素对人成纤维细胞的抗衰老性更好。因此,Anisiflupurin具有毒性低,使用安全性好的优点。The original drug of Anisiflupurin is a white crystalline powder, hardly soluble in water, slightly soluble in ethanol, and stable in acids and alkali. Anisiflupurin is a 6-anilinopurine derivative; in agriculture, it can stimulate the growth of tobacco callus and maintain the chlorophyll content in isolated wheat leaves. It can also induce the synthesis of β-anthocyanin in amaranth cotyledons. Inhibits cytokinin oxidation/dehydrogenase induced by abiotic stress. In vitro test results show that anisiflupurin has low toxicity, and its toxicity to mammalian osteosarcoma cell line HOS, breast cancer cell line MCF-7 and mouse cell line fibroblast NIH-3T3 is comparable to that of kinetin. ) is equally toxic and has better anti-aging properties than kinetin on human fibroblasts after 80 passages. Therefore, Anisiflupurin has the advantages of low toxicity and good safety in use.
目前,许多植物生长调节剂单独使用往往达不到理想的效果,单剂应用的缺点主要是生物活性比较单一、生长调节作用相对较低、使用浓度较大,而且通常只能在作物一定的生长时期才能发挥生长调节作用。因此需要正确合理地选择和混用不同的植物生长调节剂,以便克服或避免产生副作用,使之达到预期的应用效果,即达到增效、加合或诱导作用,避免拮抗作用。但是,目前国内关于Anisiflupurin与其他化合物进行复配制得的制剂尚未见有报道和登记。At present, many plant growth regulators often fail to achieve the desired effect when used alone. The main disadvantages of single-agent application are that the biological activity is relatively simple, the growth regulation effect is relatively low, the concentration is large, and it usually only works within a certain growth period of the crop. period before growth regulation can be exerted. Therefore, it is necessary to correctly and rationally select and mix different plant growth regulators in order to overcome or avoid side effects and achieve the expected application effects, that is, to achieve synergistic, additive or inducing effects and to avoid antagonism. However, there are currently no reports or registrations on preparations prepared by compounding Anisiflupurin with other compounds in China.
因此,亟需开发一种具有良好稳定性的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,从而更好地提高2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的生物活性和生长调节作用。Therefore, there is an urgent need to develop a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine with good stability to better improve 2-fluoro-N Biological activity and growth regulation of -(3-methoxyphenyl)-7H-purin-6-amine.
发明内容Contents of the invention
本发明的目的在于提供一种含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,可以解决目前单独使用2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺时存在活性单一、对植物生长调节作用不佳的问题。The object of the present invention is to provide a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine, which can solve the problem of using 2-fluoro-N-(3- Methoxyphenyl)-7H-purin-6-amine has the problem of single activity and poor plant growth regulation effect.
本发明的第二个目的在于提供一种含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,可以解决目前将2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺单独作为液体制剂使用时存在活性单一、对植物生长调节作用不佳的问题。The second object of the present invention is to provide a preparation method for a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine, which can solve the current problem of 2-fluoro- When used alone as a liquid preparation, N-(3-methoxyphenyl)-7H-purin-6-amine has the problem of single activity and poor plant growth regulation.
本发明的第三个目的在于提供一种含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂作为植物生长调节剂的应用,可以解决目前将2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺单独作为植物生长调节剂使用时存在活性单一、对植物生长调节作用不佳的问题。The third object of the present invention is to provide a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine as a plant growth regulator, which can solve the current problem of When 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine is used alone as a plant growth regulator, there is a problem of single activity and poor plant growth regulation effect.
为了实现以上目的,本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂所采用的技术方案为:In order to achieve the above objectives, the technical solution adopted by the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine of the present invention is:
一种含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,主要由活性成分、乳化剂、溶剂和助溶剂组成;所述活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和复配物组成;所述复配物为赤霉酸GA3、赤霉酸GA4+7、24-表芸苔素内酯、28-高芸苔素内酯、胺鲜酯、乙烯利或者三十烷醇;所述助溶剂为二甲基亚砜、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、乳酸;所述液体制剂中2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于10%;所述液体制剂中复配物的质量分数不大于30%。A liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine, mainly composed of active ingredients, emulsifiers, solvents and co-solvents; the active ingredient consists of 2 -Fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and a compound; the compound is gibberellic acid GA3, gibberellic acid GA4+7, 24-epiyrene Lycosinolide, 28-homobrassinolide, acetate, ethephon or triacontanol; the co-solvent is dimethyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone , lactic acid; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in the liquid preparation is not greater than 10%; the mass fraction of the compound in the liquid preparation Not more than 30%.
本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,通过将2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和不同复配物进行复配使用,同时选取特定的助溶剂,可以使液体制剂具有良好的持久起泡性、稀释稳定性、低温稳定性和热贮稳定性。本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂具有将氨基酸、生长素、无机盐等向生长部位调运的效能,可广泛用于农业、果树和园艺作物从发芽到收获的各个阶段。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of the present invention is prepared by adding 2-fluoro-N-(3-methoxyphenyl)-7H -Purine-6-amine is used in combination with different compounds, and specific co-solvents are selected at the same time, so that the liquid preparation can have good long-lasting foaming, dilution stability, low temperature stability and heat storage stability. The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine of the present invention has the effect of transporting amino acids, auxin, inorganic salts, etc. to the growth site, and can be widely used Used in all stages of agriculture, fruit trees and horticulture crops from germination to harvest.
优选地,所述复配物为赤霉酸GA3、赤霉酸GA4+7、24-表芸苔素内酯、28-高芸苔素内酯、胺鲜酯或者三十烷醇,所述液体制剂还包括稳定剂,所述稳定剂为甲酸、乙酸、乳酸、2,6-二叔丁基对甲酚、叔丁基对苯二酚。稳定剂的作用为:确保制剂在用水稀释过程中保持稀释液均一,无析出物;方便农户使用,避免堵塞农药器械的雾化喷头。Preferably, the compound is gibberellic acid GA3, gibberellic acid GA4+7, 24-epibrassinolide, 28-homobrassinolide, ampicillin or triacontanol, and the liquid preparation Stabilizers are also included, and the stabilizers are formic acid, acetic acid, lactic acid, 2,6-di-tert-butyl-p-cresol, and tert-butyl hydroquinone. The function of the stabilizer is to ensure that the dilution of the preparation remains uniform and free of precipitates during the dilution process with water; it is convenient for farmers to use and avoids clogging the atomizing nozzles of pesticide equipment.
优选地,所述复配物为赤霉酸GA3,所述液体制剂中2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA3的质量分数独立地为不大于0.9%;Preferably, the compound is gibberellic acid GA3, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and gibberellic acid GA3 in the liquid preparation Independently no more than 0.9%;
或者所述复配物为赤霉酸GA4+7,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA4+7的质量分数独立地为不大于1.8%;Or the compound is gibberellic acid GA4+7, and the liquid preparation contains 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and gibberellic acid GA4+7. The mass fraction is independently not more than 1.8%;
或者所述复配物为24-表芸苔素内酯,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.99%,24-表芸苔素内酯的质量分数不大于0.01%;Or the compound is 24-epibrassinolide, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 1.99%, the mass fraction of 24-epibrassinolide is not more than 0.01%;
或者所述复配物为28-高芸苔素内酯,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于4.995%,28-高芸苔素内酯的质量分数不大于0.005%;Or the compound is 28-homobrassinolide, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 4.995% , the mass fraction of 28-homobrassinolide is not greater than 0.005%;
或者所述复配物为胺鲜酯,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于2%,胺鲜酯的质量分数不大于8%;Or the compound is ethylamine, the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not more than 2%, and the ethylamine is The mass fraction of ester is not more than 8%;
或者所述复配物为乙烯利,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于0.5%,乙烯利的质量分数不大于29.5%;Alternatively, the compound is ethephon, the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 0.5%, and ethephon is The mass fraction is not greater than 29.5%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于9.8%,三十烷醇的质量分数不大于0.2%。不同液体制剂中,有效成分的含量过高,会造成常温储存时出现沉淀、结晶、分层等现象。Or the compound is triacontanol, the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not more than 9.8%, and the three The mass fraction of decanol is not greater than 0.2%. In different liquid preparations, the content of active ingredients is too high, which will cause precipitation, crystallization, stratification and other phenomena when stored at room temperature.
优选地,所述复配物为赤霉酸GA3,所述稳定剂为甲酸和/或乳酸;所述液体制剂中稳定剂的质量分数为0.5~2%;Preferably, the compound is gibberellic acid GA3, and the stabilizer is formic acid and/or lactic acid; the mass fraction of the stabilizer in the liquid preparation is 0.5 to 2%;
或者所述复配物为赤霉酸GA4+7,所述稳定剂为甲酸和/或乳酸;所述液体制剂中的稳定剂的质量分数为10~20%;Or the compound is gibberellic acid GA4+7, and the stabilizer is formic acid and/or lactic acid; the mass fraction of the stabilizer in the liquid preparation is 10 to 20%;
或者所述复配物为24-表芸苔素内酯,所述稳定剂为甲酸和/或乙酸;所述液体制剂中的稳定剂的质量分数为3~6%;Or the compound is 24-epibrassinolide, and the stabilizer is formic acid and/or acetic acid; the mass fraction of the stabilizer in the liquid preparation is 3 to 6%;
或者所述复配物为28-高芸苔素内酯,所述稳定剂为甲酸和/或乙酸;所述液体制剂中的稳定剂的质量分数为0.3~0.6%;Or the compound is 28-homobrassinolide, and the stabilizer is formic acid and/or acetic acid; the mass fraction of the stabilizer in the liquid preparation is 0.3 to 0.6%;
或者所述复配物为胺鲜酯,所述稳定剂为2,6-二叔丁基对甲酚或者叔丁基对苯二酚;所述液体制剂中的稳定剂的质量分数为1~3%;Alternatively, the compound is ethylenimine, and the stabilizer is 2,6-di-tert-butyl-p-cresol or tert-butyl hydroquinone; the mass fraction of the stabilizer in the liquid preparation is 1 to 3%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.9%,所述液体制剂中的三十烷醇的质量分数不大于0.1%,所述液体制剂中的稳定剂为乙酸;所述液体制剂中的稳定剂的质量分数为1~3%;Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 1.9%, so The mass fraction of triacontanol in the liquid preparation is not greater than 0.1%, the stabilizer in the liquid preparation is acetic acid; the mass fraction of the stabilizer in the liquid preparation is 1 to 3%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数>1.9%且≤9.8%,所述液体制剂中的三十烷醇的质量分数>0.1%且≤0.2%,所述液体制剂中的稳定剂为甲酸;所述液体制剂中的稳定剂的质量分数为6~10%。稳定剂的类型和用量对液体制剂的物理稳定性有重要影响,对于不同的复配物,需要使用相应的稳定剂以及相应的稳定剂用量,如果改变稳定剂的类型和用量,将导致液体制剂的性能不达标。当稳定剂用量过多时,会造成制剂pH值过低,造成有效成分分解等问题;当稳定剂用量过少时,会造成制剂的水稀释液有沉淀出现,稀释稳定性不合格。Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is >1.9% and ≤9.8 %, the mass fraction of triacontanol in the liquid preparation is >0.1% and ≤0.2%, the stabilizer in the liquid preparation is formic acid; the mass fraction of the stabilizer in the liquid preparation is 6 to 10% . The type and dosage of stabilizers have an important impact on the physical stability of liquid preparations. For different compounds, corresponding stabilizers and corresponding stabilizer dosages need to be used. If the type and dosage of stabilizers are changed, the liquid preparation will be The performance is not up to standard. When the amount of stabilizer is too much, the pH value of the preparation will be too low, causing decomposition of the active ingredients and other problems; when the amount of stabilizer is too small, precipitation will occur in the water dilution of the preparation, and the dilution stability will be unqualified.
优选地,所述复配物为赤霉酸GA3,所述液体制剂中的乳化剂为辛基酚聚氧乙烯醚和/或脂肪醇聚氧乙烯醚;所述液体制剂中的乳化剂的质量分数为1~4%;Preferably, the compound is gibberellic acid GA3, and the emulsifier in the liquid preparation is octylphenol polyoxyethylene ether and/or fatty alcohol polyoxyethylene ether; the quality of the emulsifier in the liquid preparation is The score is 1 to 4%;
或者所述复配物为赤霉酸GA4+7,所述液体制剂中的乳化剂为辛基酚聚氧乙烯醚和/或脂肪醇聚氧乙烯醚;所述液体制剂中的乳化剂的质量分数为2~4%;Or the compound is gibberellic acid GA4+7, and the emulsifier in the liquid preparation is octylphenol polyoxyethylene ether and/or fatty alcohol polyoxyethylene ether; the quality of the emulsifier in the liquid preparation The score is 2 to 4%;
或者所述复配物为24-表芸苔素内酯,所述液体制剂中的乳化剂为吐温80;所述液体制剂中的乳化剂的质量分数为3~7%;Or the compound is 24-epibrassinolide, and the emulsifier in the liquid preparation is Tween 80; the mass fraction of the emulsifier in the liquid preparation is 3 to 7%;
或者所述复配物为28-高芸苔素内酯,所述液体制剂中的乳化剂为聚乙二醇400;所述液体制剂中的乳化剂的质量分数为4~8%;Or the compound is 28-homobrassinolide, the emulsifier in the liquid preparation is polyethylene glycol 400; the mass fraction of the emulsifier in the liquid preparation is 4 to 8%;
或者所述复配物为胺鲜酯,所述液体制剂中的乳化剂为聚醚;所述液体制剂中的乳化剂的质量分数为0.5~2%;Or the compound is ethyl ethyl, and the emulsifier in the liquid preparation is polyether; the mass fraction of the emulsifier in the liquid preparation is 0.5 to 2%;
或者所述复配物为乙烯利,所述液体制剂中的乳化剂为聚乙二醇400;所述液体制剂中的乳化剂的质量分数为3~6%;Or the compound is ethephon, and the emulsifier in the liquid preparation is polyethylene glycol 400; the mass fraction of the emulsifier in the liquid preparation is 3 to 6%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.9%,所述液体制剂中的乳化剂为脂肪醇聚氧乙烯醚;所述液体制剂中的乳化剂的质量分数为2~6%;Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 1.9%, so The emulsifier in the liquid preparation is fatty alcohol polyoxyethylene ether; the mass fraction of the emulsifier in the liquid preparation is 2 to 6%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数>1.9%且≤9.8%,所述液体制剂中的三十烷醇的质量分数>0.1%且≤0.2%,所述液体制剂中的乳化剂为吐温80;所述液体制剂中的乳化剂的质量分数为3~7%。乳化剂的作用为:降低混合体系中各组分的界面张力,并在微滴表面形成较坚固的薄膜或通过乳化剂给出的电荷而在微滴表面形成双电层,阻止微滴彼此聚集,从而保持均匀的状态。对于不同的复配物,需要使用对应的乳化剂以及对应的乳化剂用量,当乳化剂用量过多时,会造成:制剂体系粘度过大,不利于实际生产时的灌装和计量;同时低温容易出现制剂混浊现象;使用量过多,制剂渗透性过强,亦会对作物产生药害。当乳化剂用量过少时,会造成:制剂有效成分微滴聚集、絮凝,进而产生晶体析出、沉淀的不合格现象。Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is >1.9% and ≤9.8 %, the mass fraction of triacontanol in the liquid preparation is >0.1% and ≤0.2%, the emulsifier in the liquid preparation is Tween 80; the mass fraction of the emulsifier in the liquid preparation is 3~ 7%. The function of the emulsifier is to reduce the interfacial tension of each component in the mixed system and form a stronger film on the surface of the droplets or form a double electrical layer on the surface of the droplets through the charge given by the emulsifier to prevent the droplets from aggregating with each other. , thereby maintaining a uniform state. For different compounds, corresponding emulsifiers and corresponding amounts of emulsifiers need to be used. When the amount of emulsifier is too much, it will cause: the viscosity of the preparation system is too high, which is not conducive to filling and metering in actual production; at the same time, low temperature is easy to There will be turbidity in the preparation; too much dosage and too strong permeability of the preparation will cause phytotoxicity to crops. When the amount of emulsifier is too small, it will cause: the droplets of the active ingredients of the preparation aggregate and flocculate, resulting in the unqualified phenomenon of crystal precipitation and precipitation.
优选地,所述复配物为赤霉酸GA3,所述液体制剂中的助溶剂为二甲基亚砜;所述液体制剂中的助溶剂的质量分数为15~25%;Preferably, the compound is gibberellic acid GA3, and the co-solvent in the liquid preparation is dimethyl sulfoxide; the mass fraction of the co-solvent in the liquid preparation is 15 to 25%;
或者所述复配物为赤霉酸GA4+7,所述液体制剂中的助溶剂为N,N-二甲基甲酰胺;所述液体制剂中的助溶剂的质量分数为30~40%;Or the compound is gibberellic acid GA4+7, and the co-solvent in the liquid preparation is N,N-dimethylformamide; the mass fraction of the co-solvent in the liquid preparation is 30 to 40%;
或者所述复配物为24-表芸苔素内酯,所述液体制剂中的助溶剂为N-甲基吡咯烷酮和/或二甲基亚砜;所述液体制剂中的助溶剂的质量分数为10~20%;Or the compound is 24-epibrassinolide, and the co-solvent in the liquid preparation is N-methylpyrrolidone and/or dimethyl sulfoxide; the mass fraction of the co-solvent in the liquid preparation is 10~20%;
或者所述复配物为28-高芸苔素内酯,所述液体制剂中的助溶剂为N-甲基吡咯烷酮和/或二甲基亚砜;所述液体制剂中的助溶剂的质量分数为20~40%;Or the compound is 28-homobrassinolide, the co-solvent in the liquid preparation is N-methylpyrrolidone and/or dimethyl sulfoxide; the mass fraction of the co-solvent in the liquid preparation is 20 ~40%;
或者所述复配物为胺鲜酯,所述液体制剂中的助溶剂为N-甲基吡咯烷酮;所述液体制剂中的助溶剂的质量分数为20~30%;Or the compound is ethyl acetate, and the co-solvent in the liquid preparation is N-methylpyrrolidone; the mass fraction of the co-solvent in the liquid preparation is 20 to 30%;
或者所述复配物为乙烯利,所述液体制剂中的助溶剂为乳酸;所述液体制剂中的助溶剂的质量分数为30~40%;Or the compound is ethephon, the co-solvent in the liquid preparation is lactic acid; the mass fraction of the co-solvent in the liquid preparation is 30 to 40%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.9%,所述液体制剂中的三十烷醇的质量分数不大于0.1%,所述液体制剂中的助溶剂为二甲基亚砜;所述液体制剂中的助溶剂的质量分数为10~20%;Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 1.9%, so The mass fraction of triacontanol in the liquid preparation is not greater than 0.1%, the co-solvent in the liquid preparation is dimethyl sulfoxide; the mass fraction of the co-solvent in the liquid preparation is 10 to 20%;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数>1.9%且≤9.8%,所述液体制剂中的三十烷醇的质量分数>0.1%且≤0.2%,所述液体制剂中的助溶剂为N-甲基吡咯烷酮;所述液体制剂中的助溶剂的质量分数为30~40%。助溶剂的作用为溶解液体制剂中的有效成分,并且可与难溶性物质形成络合物、缔合物或复盐等,以增加药物在溶剂中的溶解度。助溶剂亦能增加制剂的稳定性,改善物理性,矫臭矫味,减轻刺激,改善吸收,增加药理作用。助溶剂用量过少,会造成制剂有效成分溶解不完全,易出现晶体析出、沉淀等不稳定现象。Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is >1.9% and ≤9.8 %, the mass fraction of triacontanol in the liquid preparation is >0.1% and ≤0.2%, the co-solvent in the liquid preparation is N-methylpyrrolidone; the mass fraction of the co-solvent in the liquid preparation is 30~40%. The role of co-solvent is to dissolve the active ingredients in liquid preparations, and can form complexes, associations or double salts with insoluble substances to increase the solubility of the drug in the solvent. Co-solvents can also increase the stability of preparations, improve physical properties, correct smell and taste, reduce irritation, improve absorption, and increase pharmacological effects. If the amount of co-solvent is too small, the active ingredients of the preparation will not be completely dissolved, and unstable phenomena such as crystal precipitation and precipitation will easily occur.
优选地,所述复配物为赤霉酸GA3,所述液体制剂中的溶剂为醇类溶剂,所述醇类溶剂为乙二醇和/或丙二醇;Preferably, the compound is gibberellic acid GA3, the solvent in the liquid preparation is an alcoholic solvent, and the alcoholic solvent is ethylene glycol and/or propylene glycol;
或者所述复配物为赤霉酸GA4+7,所述液体制剂中的溶剂为醇类溶剂,所述醇类溶剂为乙二醇和/或丙二醇;Or the compound is gibberellic acid GA4+7, the solvent in the liquid preparation is an alcoholic solvent, and the alcoholic solvent is ethylene glycol and/or propylene glycol;
或者所述复配物为24-表芸苔素内酯,所述液体制剂中的溶剂为丙二醇;Or the compound is 24-epibrassinolide, and the solvent in the liquid preparation is propylene glycol;
或者所述复配物为28-高芸苔素内酯,所述液体制剂中的溶剂为N,N-二甲基甲酰胺;Or the compound is 28-homobrassinolide, and the solvent in the liquid preparation is N,N-dimethylformamide;
或者所述复配物为胺鲜酯,所述液体制剂中的溶剂为N,N-二甲基甲酰胺;Or the compound is ethylcarboxylate, and the solvent in the liquid preparation is N,N-dimethylformamide;
或者所述复配物为乙烯利,所述液体制剂中的溶剂选自水、乙二醇、丙二醇中的一种或任意组合;Or the compound is ethephon, and the solvent in the liquid preparation is selected from one or any combination of water, ethylene glycol, and propylene glycol;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.9%,所述液体制剂中的三十烷醇的质量分数不大于0.1%,所述液体制剂中的溶剂为丙二醇;Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is not greater than 1.9%, so The mass fraction of triacontanol in the liquid preparation is not greater than 0.1%, and the solvent in the liquid preparation is propylene glycol;
或者所述复配物为三十烷醇,所述液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数>1.9%且≤9.8%,所述液体制剂中的三十烷醇的质量分数>0.1%且≤0.2%,所述液体制剂中的溶剂为N,N-二甲基甲酰胺。液体制剂中的溶剂具有以下作用:①稀释作用:溶剂可以将浓缩的物质稀释,使得其更易于操作或处理。②溶解作用:能够溶解不溶于水的物质,使其变成可溶性的物质。③稳定作用:溶剂可以稳定某些物质,使其不易被氧化或分解。④改变物质的物理性质:溶剂可以改变物质的物理性质,如粘度、表面张力等,使其更易于操作或处理。溶剂用量过少,会造成:制剂有效成分的溶解度偏低,溶解不完全,进而产生晶体析出。Or the compound is triacontanol, and the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the liquid preparation is >1.9% and ≤9.8 %, the mass fraction of triacontanol in the liquid preparation is >0.1% and ≤0.2%, and the solvent in the liquid preparation is N,N-dimethylformamide. Solvents in liquid preparations have the following functions: ① Dilution: Solvents can dilute concentrated substances, making them easier to operate or handle. ②Dissolution: It can dissolve substances that are insoluble in water and turn them into soluble substances. ③Stabilizing effect: Solvents can stabilize certain substances so that they are not easily oxidized or decomposed. ④Change the physical properties of a substance: Solvents can change the physical properties of a substance, such as viscosity, surface tension, etc., making it easier to operate or handle. If the amount of solvent is too small, the solubility of the active ingredients of the preparation will be low and the dissolution will be incomplete, resulting in crystal precipitation.
优选地,所述液体制剂为A组合物、B组合物、C组合物、D组合物、E组合物、F组合物或G组合物;Preferably, the liquid preparation is A composition, B composition, C composition, D composition, E composition, F composition or G composition;
所述A组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述A组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA3组成;所述A组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA3的质量分数独立地为不大于0.9%;所述A组合物中的稳定剂为甲酸和/或乳酸;所述A组合物中的稳定剂的质量分数为0.5~2%;所述A组合物中的乳化剂为辛基酚聚氧乙烯醚和/或脂肪醇聚氧乙烯醚;所述A组合物中的乳化剂的质量分数为1~4%;所述A组合物中的溶剂为醇类溶剂;所述A组合物中的溶剂为乙二醇和/或丙二醇;所述A组合物中的助溶剂为二甲基亚砜;所述A组合物中的助溶剂的质量分数为15~25%;The A composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the A composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Composed of purine-6-amine and gibberellic acid GA3; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and gibberellic acid GA3 in the A composition Independently, it is no more than 0.9%; the stabilizer in the A composition is formic acid and/or lactic acid; the mass fraction of the stabilizer in the A composition is 0.5 to 2%; the emulsification in the A composition The agent is octylphenol polyoxyethylene ether and/or fatty alcohol polyoxyethylene ether; the mass fraction of the emulsifier in the composition A is 1 to 4%; the solvent in the composition A is an alcohol solvent; The solvent in the A composition is ethylene glycol and/or propylene glycol; the co-solvent in the A composition is dimethyl sulfoxide; the mass fraction of the co-solvent in the A composition is 15 to 25%;
所述B组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述B组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA4+7组成;所述B组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和赤霉酸GA4+7的质量分数独立地为不大于1.8%;所述B组合物中的稳定剂为甲酸和/或乳酸;所述B组合物中的稳定剂的质量分数为10~20%;所述B组合物中的乳化剂为辛基酚聚氧乙烯醚和/或脂肪醇聚氧乙烯醚;所述B组合物中的乳化剂的质量分数为2~4%;所述B组合物中的溶剂为醇类溶剂;所述B组合物中的溶剂为乙二醇和/或丙二醇;所述B组合物中的助溶剂为N,N-二甲基甲酰胺;所述B组合物中的助溶剂的质量分数为30~40%;The B composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the B composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Composed of purine-6-amine and gibberellic acid GA4+7; 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine and gibberellic acid GA4+ in the B composition The mass fraction of 7 is independently no more than 1.8%; the stabilizer in the B composition is formic acid and/or lactic acid; the mass fraction of the stabilizer in the B composition is 10 to 20%; the B combination The emulsifier in the composition is octylphenol polyoxyethylene ether and/or fatty alcohol polyoxyethylene ether; the mass fraction of the emulsifier in the B composition is 2 to 4%; the solvent in the B composition is Alcohol solvent; the solvent in the B composition is ethylene glycol and/or propylene glycol; the co-solvent in the B composition is N,N-dimethylformamide; the co-solvent in the B composition is The mass fraction is 30~40%;
所述C组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述C组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和24-表芸苔素内酯组成;所述C组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.99%,所述24-表芸苔素内酯的质量分数不大于0.01%;所述C组合物中的稳定剂为甲酸和/或乙酸;所述C组合物中的稳定剂的质量分数为3~6%;所述C组合物中的乳化剂为吐温80;所述C组合物中的乳化剂的质量分数为3~7%;所述C组合物中的溶剂为丙二醇;所述C组合物中的助溶剂为N-甲基吡咯烷酮和/或二甲基亚砜;所述C组合物中的助溶剂的质量分数为10~20%;The C composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the C composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Purine-6-amine and 24-epibrassinolide; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in the C composition is not Greater than 1.99%, the mass fraction of the 24-epibrassinolide is not greater than 0.01%; the stabilizer in the C composition is formic acid and/or acetic acid; the mass fraction of the stabilizer in the C composition is 3 to 6%; the emulsifier in the C composition is Tween 80; the mass fraction of the emulsifier in the C composition is 3 to 7%; the solvent in the C composition is propylene glycol; The co-solvent in the C composition is N-methylpyrrolidone and/or dimethyl sulfoxide; the mass fraction of the co-solvent in the C composition is 10 to 20%;
所述D组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述D组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和28-高芸苔素内酯组成;所述D组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于4.995%,所述28-高芸苔素内酯的质量分数不大于0.005%;所述D组合物中的稳定剂为甲酸和/或乙酸;所述D组合物中的稳定剂的质量分数为0.3~0.6%;所述D组合物中的乳化剂为聚乙二醇400;所述D组合物中的乳化剂的质量分数为4~8%;所述D组合物中的溶剂为N,N-二甲基甲酰胺;所述D组合物中的助溶剂为N-甲基吡咯烷酮和/或二甲基亚砜;所述D组合物中的助溶剂的质量分数为20~40%;The D composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the D composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Composed of purine-6-amine and 28-homobrassinolide; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in the D composition is not greater than 4.995 %, the mass fraction of the 28-homobrassinolide is not greater than 0.005%; the stabilizer in the D composition is formic acid and/or acetic acid; the mass fraction of the stabilizer in the D composition is 0.3 to 0.6 %; the emulsifier in the D composition is polyethylene glycol 400; the mass fraction of the emulsifier in the D composition is 4 to 8%; the solvent in the D composition is N,N-di Methyl formamide; the co-solvent in the D composition is N-methylpyrrolidone and/or dimethyl sulfoxide; the mass fraction of the co-solvent in the D composition is 20 to 40%;
所述E组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述E组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和胺鲜酯组成;所述E组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于2%;所述E组合物中的胺鲜酯的质量分数不大于8%;所述E组合物中的稳定剂为2,6-二叔丁基对甲酚和/或叔丁基对苯二酚;所述E组合物中的稳定剂的质量分数为1~3%;所述E组合物中的乳化剂为聚醚;所述E组合物中的乳化剂的质量分数为0.5~2%;所述E组合物中的溶剂为N,N-二甲基甲酰胺;所述E组合物中的助溶剂为N-甲基吡咯烷酮;所述E组合物中的助溶剂的质量分数为20~30%;所述聚醚为EO/PO嵌段聚醚;The E composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the E composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Composed of purine-6-amine and ammonium ester; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in the E composition is not more than 2%; so The mass fraction of ethyl ester in the E composition is not more than 8%; the stabilizer in the E composition is 2,6-di-tert-butyl-p-cresol and/or tert-butyl hydroquinone; so The mass fraction of the stabilizer in the E composition is 1 to 3%; the emulsifier in the E composition is polyether; the mass fraction of the emulsifier in the E composition is 0.5 to 2%; The solvent in the E composition is N,N-dimethylformamide; the co-solvent in the E composition is N-methylpyrrolidone; the mass fraction of the co-solvent in the E composition is 20 to 30% ; The polyether is an EO/PO block polyether;
所述F组合物主要由活性成分、乳化剂、溶剂和助溶剂组成;所述F组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和乙烯利组成;所述F组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于0.5%;所述F组合物中的乙烯利的质量分数不大于29.5%;所述F组合物中的乳化剂为聚乙二醇400;所述F组合物中的乳化剂的质量分数为3~6%;所述F组合物中的溶剂选自水、乙二醇、丙二醇中的一种或任意组合;所述F组合物中的助溶剂为乳酸;所述F组合物中的助溶剂的质量分数为30~40%;The F composition mainly consists of active ingredients, emulsifiers, solvents and co-solvents; the active ingredient in the F composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6 -Composed of amine and ethephon; the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in the F composition is not greater than 0.5%; the F composition The mass fraction of ethephon in the F composition is not more than 29.5%; the emulsifier in the F composition is polyethylene glycol 400; the mass fraction of the emulsifier in the F composition is 3 to 6%; the F combination The solvent in the composition is selected from one or any combination of water, ethylene glycol, and propylene glycol; the co-solvent in the F composition is lactic acid; the mass fraction of the co-solvent in the F composition is 30 to 40% ;
所述G组合物主要由活性成分、稳定剂、乳化剂、溶剂和助溶剂组成;所述G组合物中的活性成分由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和三十烷醇组成;The G composition mainly consists of active ingredients, stabilizers, emulsifiers, solvents and co-solvents; the active ingredient in the G composition consists of 2-fluoro-N-(3-methoxyphenyl)-7H- Composed of purine-6-amine and triacontanol;
所述G组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数不大于1.9%,所述G组合物中的三十烷醇的质量分数不大于0.1%,所述G组合物中的稳定剂为乙酸;所述G组合物中的稳定剂的质量分数为1~3%;所述G组合物中的乳化剂为脂肪醇聚氧乙烯醚;所述G组合物中的乳化剂的质量分数为2~6%;所述G组合物中的溶剂为丙二醇;所述G组合物中的助溶剂为二甲基亚砜;所述G组合物中的助溶剂的质量分数为10~20%;The mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the G composition is not greater than 1.9%, and the mass fraction of triacontanol in the G composition is The mass fraction is not more than 0.1%, the stabilizer in the G composition is acetic acid; the mass fraction of the stabilizer in the G composition is 1 to 3%; the emulsifier in the G composition is fatty alcohol poly Oxyethylene ether; the mass fraction of the emulsifier in the G composition is 2 to 6%; the solvent in the G composition is propylene glycol; the co-solvent in the G composition is dimethyl sulfoxide; The mass fraction of the co-solvent in the G composition is 10 to 20%;
或者所述G组合物中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数>1.9%且≤9.8%,所述G组合物中的三十烷醇的质量分数>0.1%且≤0.2%,所述G组合物中的稳定剂为甲酸;所述G组合物中的稳定剂的质量分数为6~10%;所述G组合物中的乳化剂为吐温80;所述G组合物中的乳化剂的质量分数为3~7%;所述G组合物中的溶剂为N,N-二甲基甲酰胺;所述G组合物中的助溶剂为N-甲基吡咯烷酮;所述G组合物中的助溶剂的质量分数为30~40%。Or the mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in the G composition is >1.9% and ≤9.8%, and the three The mass fraction of decanol is >0.1% and ≤0.2%, and the stabilizer in the G composition is formic acid; the mass fraction of the stabilizer in the G composition is 6 to 10%; The emulsifier is Tween 80; the mass fraction of the emulsifier in the G composition is 3 to 7%; the solvent in the G composition is N,N-dimethylformamide; the G composition The co-solvent in the G composition is N-methylpyrrolidone; the mass fraction of the co-solvent in the G composition is 30 to 40%.
E组合物中的乳化剂可以采用市售产品,例如,南京捷润科技有限公司生产的型号为Ethylan NS-500LQ的产品,该产品为非离子型羟基聚环氧乙烷嵌段共聚物,EO/PO的摩尔比为1:1.71,pH为6.5~7.5,具有良好的乳化润湿分散功能。The emulsifier in the E composition can be commercially available products, for example, the product model Ethylan NS-500LQ produced by Nanjing Jierun Technology Co., Ltd. This product is a non-ionic hydroxyl polyethylene oxide block copolymer, EO The molar ratio of /PO is 1:1.71, the pH is 6.5-7.5, and it has good emulsifying, wetting and dispersing functions.
本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法所采用的技术方案为:The technical solution adopted in the preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine of the present invention is:
如上所述的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,包括以下步骤:将配方量的各组分混合均匀,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine as described above includes the following steps: Mix the components of the formula evenly to obtain Liquid formulation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,操作简单,制备的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂具有良好的持久起泡性、稀释稳定性、低温稳定性和热贮稳定性。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine of the present invention is simple to operate, and the prepared liquid preparation containing 2-fluoro-N-(3-methyl The liquid preparation of oxyphenyl)-7H-purin-6-amine has good long-lasting foaming properties, dilution stability, low temperature stability and heat storage stability.
优选地,所述混合均匀的方法包括以下步骤:将各组合物中的活性成分溶解于助溶剂中,然后再加入其它各组分,混匀。Preferably, the method of uniform mixing includes the following steps: dissolving the active ingredients in each composition in a co-solvent, then adding other components and mixing.
本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂作为植物生长调节剂的应用所采用的技术方案为:The technical solution adopted for the application of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine as a plant growth regulator of the present invention is:
一种如上所述的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂作为植物生长调节剂的应用。Use of a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine as described above as a plant growth regulator.
将本发明的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂作为植物生长调节剂,可以有效地促进植物生长。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of the present invention can be used as a plant growth regulator to effectively promote plant growth.
一种如上所述的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂在促进植物生长中的应用。Use of a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine as described above in promoting plant growth.
优选地,所述液体制剂为A组合物和/或B组合物,所述液体制剂具有促进胚芽鞘生长的作用。进一步优选地,所述液体制剂为A组合物和/或B组合物,所述液体制剂具有促进燕麦胚芽鞘生长的作用。Preferably, the liquid preparation is composition A and/or composition B, and the liquid preparation has the effect of promoting the growth of coleoptiles. Further preferably, the liquid preparation is composition A and/or composition B, and the liquid preparation has the effect of promoting the growth of oat coleoptiles.
优选地,所述液体制剂为C组合物和/或D组合物,所述液体制剂具有提高植物株高和/或提高植物叶片中营养成分的含量的作用,所述营养成分选自叶绿素、蛋白质和脂肪中的一种或任意组合。进一步优选地,所述液体制剂为C组合物和/或D组合物,所述液体制剂具有提高植物株高和/或提高植物叶片中营养成分的含量的作用,所述营养成分选自叶绿素、蛋白质和脂肪中的一种或任意组合。优选地,所述液体制剂为C组合物和/或D组合物,所述食物为花生。Preferably, the liquid preparation is composition C and/or composition D. The liquid preparation has the effect of increasing plant height and/or increasing the content of nutrients in plant leaves. The nutrients are selected from chlorophyll, protein. and fats alone or in any combination. Further preferably, the liquid preparation is composition C and/or composition D, and the liquid preparation has the effect of increasing plant height and/or increasing the content of nutrient components in plant leaves, and the nutrient components are selected from the group consisting of chlorophyll, One or any combination of protein and fat. Preferably, the liquid preparation is composition C and/or composition D, and the food is peanuts.
优选地,所述液体制剂为E组合物和/或F组合物,所述液体制剂具有提高植物坐果率和/或提高植物果实品质的作用,所述植物果实品质为单果过重和/或果实中的维生素C含量。进一步优选地,所述液体制剂为E组合物和/或F组合物,所述液体制剂具有提高苹果坐果率和/或提高苹果果实品质的作用,所述苹果果实品质为单果过重和/或果实中的维生素C含量。Preferably, the liquid preparation is E composition and/or F composition, and the liquid preparation has the effect of increasing the plant fruit setting rate and/or improving the plant fruit quality. The plant fruit quality is overweight per fruit and/or fruit. Vitamin C content in . Further preferably, the liquid preparation is the E composition and/or the F composition, and the liquid preparation has the effect of increasing the apple fruit setting rate and/or improving the apple fruit quality, and the apple fruit quality is overweight per fruit and/or Vitamin C content in the fruit.
优选地,所述液体制剂为G组合物,所述液体制剂具有提高植物果实体积和/或重量的作用。优选地,所述液体制剂为G组合物,所述液体制剂具有提高植物果实直径的作用。进一步优选地,所述液体制剂为G组合物,所述液体制剂具有提高芒果果实的纵径和/或横径的作用。Preferably, the liquid preparation is G composition, and the liquid preparation has the effect of increasing the volume and/or weight of plant fruits. Preferably, the liquid preparation is G composition, and the liquid preparation has the effect of increasing plant fruit diameter. Further preferably, the liquid preparation is G composition, and the liquid preparation has the effect of increasing the longitudinal diameter and/or transverse diameter of mango fruit.
具体实施方式Detailed ways
下面结合具体实施例对本发明的技术方案进行进一步说明。The technical solution of the present invention will be further described below with reference to specific embodiments.
实施例1-8中液体制剂的pH值按照标准GB/T 1601中的规定进行测试;The pH value of the liquid preparations in Examples 1-8 was tested in accordance with the provisions of standard GB/T 1601;
持久起泡性按照标准GB/T 28137中的规定进行测试,测试时记录1min时的泡沫体积,当泡沫体积不大于40mL时,持久起泡性测试结果为合格,否则为不合格;The durable foaming property is tested in accordance with the provisions of the standard GB/T 28137. The foam volume at 1 minute is recorded during the test. When the foam volume is not greater than 40mL, the durable foaming property test result is qualified, otherwise it is unqualified;
稀释稳定性的测试方法如下:用移液管吸取5mL试样(液体制剂),置于100mL量筒中,用标准硬水稀释至100mL,摇匀,将此量筒放入30±2℃恒温水浴中,静置1h,观察量筒中的稀释液的外观,如果稀释液中有固体颗粒析出,则稀释稳定性测试结果为不合格,如果稀释液中无固体颗粒析出,则稀释稳定性测试结果为合格;标准硬水按标准GB/T 14825中的规定配制;The test method for dilution stability is as follows: Use a pipette to absorb 5 mL of sample (liquid preparation), place it in a 100 mL graduated cylinder, dilute it to 100 mL with standard hard water, shake well, and place the graduated cylinder in a constant temperature water bath of 30±2°C. Let it stand for 1 hour and observe the appearance of the diluent in the graduated cylinder. If there are solid particles precipitating in the diluent, the dilution stability test result is unqualified. If there are no solid particles precipitating in the diluent, the dilution stability test result is qualified; Standard hard water is prepared according to the regulations in standard GB/T 14825;
低温稳定性按照标准GB/T 19137中“乳剂和均相液体制剂”的方法进行测试,具体方法如下:将100mL的液体制剂放入烧杯中,然后将烧杯在0±2℃下冷贮7天,后将烧杯取出,恢复至室温,观察杯内有无油状物析出,并测定析出的油状物的体积,如果无油状物析出或者析出的油状物的体积不超过0.3mL,则低温稳定性测试结果为合格,如果析出的油状物的体积超过0.3mL,则低温稳定性测试结果为不合格;The low-temperature stability is tested according to the method of "emulsions and homogeneous liquid preparations" in the standard GB/T 19137. The specific method is as follows: put 100mL of liquid preparation into a beaker, and then cold store the beaker at 0±2℃ for 7 days , then take out the beaker and return it to room temperature. Observe whether there is any oil precipitated in the cup, and measure the volume of the precipitated oil. If no oil precipitates or the volume of the precipitated oil does not exceed 0.3mL, perform a low-temperature stability test. The result is qualified. If the volume of precipitated oil exceeds 0.3mL, the low temperature stability test result is unqualified;
热贮稳定性的测试方法如下:量取30mL试样(液体制剂),按标准GB/T 19136中“液体制剂”的方法进行测试,具体方法如下:将试样用注射器注入洁净的安瓿瓶中,并用高温火焰封口,再将封闭的安瓿瓶置于54±2℃的恒温箱中贮存14天,取出,恢复至室温,测量试样的质量,如果试样的质量未变化,再于24h内测定试样中有效成分的质量分数、试样的pH值和稀释稳定性,如果有效成分的质量分数不低于热贮前的95%,且热贮后的试样的pH值和稀释稳定性的测试结果均为合格,则热贮稳定性的测试结果为合格。The test method for thermal storage stability is as follows: measure 30 mL of sample (liquid preparation) and conduct the test according to the "liquid preparation" method in standard GB/T 19136. The specific method is as follows: Inject the sample into a clean ampoule bottle with a syringe , and seal it with a high-temperature flame, then place the closed ampoule in a constant temperature oven at 54±2°C for 14 days, take it out, return it to room temperature, and measure the mass of the sample. If the mass of the sample does not change, store it again within 24 hours. Determine the mass fraction of the active ingredient in the sample, the pH value and dilution stability of the sample, if the mass fraction of the active ingredient is not less than 95% of that before heat storage, and the pH value and dilution stability of the sample after heat storage The test results are all qualified, then the test results of thermal storage stability are qualified.
有效成分的质量分数采用液相色谱-紫外检测器进行测试,其中,液相色谱仪器为安捷伦1260高效液相色谱仪,紫外仪器为具有可调紫外波长检测器;色谱柱150mm×4.6mm(id),C18 5μm填料;微量进样器25μL;色谱条件:流动相为甲醇+水+乙酸=40+60+0.1(V/V/V),经超声脱气并过滤;流速为1.0mL/min;柱温为25±2℃;检测波长为210nm;进样体积为5μL。The mass fraction of the active ingredients was tested using a liquid chromatography-ultraviolet detector. The liquid chromatography instrument was an Agilent 1260 high performance liquid chromatograph, and the ultraviolet instrument was a detector with an adjustable ultraviolet wavelength; the chromatographic column was 150 mm × 4.6 mm (id ), C18 5μm packing; micro injector 25μL; chromatographic conditions: mobile phase is methanol + water + acetic acid = 40 + 60 + 0.1 (V/V/V), degassed and filtered by ultrasonic; flow rate is 1.0mL/min ;The column temperature is 25±2℃; the detection wavelength is 210nm; the injection volume is 5μL.
实施例1Example 1
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、赤霉酸、稳定剂、乳化剂、溶剂和助溶剂组成;赤霉酸、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表1所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H -Purine-6-amine (Anisiflupurin), gibberellic acid, stabilizer, emulsifier, solvent and co-solvent composition; types of gibberellic acid, stabilizer, emulsifier, solvent and co-solvent and the mass fraction of each component such as As shown in Table 1.
表1实施例1的液体制剂中赤霉酸、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 1 Types of gibberellic acid, stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 1 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为80转/min,边搅拌边加入Anisiflupurin、赤霉酸,加入完毕后,再搅拌30min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌60min,最后再加入溶剂,继续搅拌30min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 80 rpm. Add Anisiflupurin and gibberellic acid while stirring. After the addition is completed, stir for another 30 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add stabilizer, emulsifier, continue stirring for 60 min, finally add the solvent, continue stirring for 30 min, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、赤霉酸完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing the liquid preparation, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and gibberellic acid, the stirring time is controlled to 30-60 min; after adding the stabilizer and emulsifier, the stirring time is controlled is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、赤霉酸的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表2所示。The liquid preparation of this example was tested for Anisiflupurin and gibberellic acid content, pH value, long-lasting foaming property, dilution stability, low temperature stability and thermal storage stability. The results are shown in Table 2.
表2实施例1的液体制剂的性能测试结果Table 2 Performance test results of the liquid formulation of Example 1
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入20g的助溶剂,准确称取Anisiflupurin 0.9g、赤霉酸GA3 0.9g,在转速为80转/min的条件下,搅拌溶解30min,观察Anisiflupurin、赤霉酸GA3的溶解情况,结果如表3所示。In order to examine the impact of different co-solvents on liquid preparations, add 20 g of co-solvents to the mixing device, accurately weigh 0.9 g of Anisiflupurin and 0.9 g of gibberellic acid GA3, and stir and dissolve for 30 minutes at a speed of 80 rpm. , observe the dissolution of Anisiflupurin and gibberellic acid GA3, and the results are shown in Table 3.
表3不同助溶剂对Anisiflupurin、赤霉酸GA3的溶解情况Table 3 Dissolution of Anisiflupurin and gibberellic acid GA3 by different co-solvents
由表3可知,使用相同质量的无水乙醇、环己酮、丙二醇甲醚醋酸酯、N,N-二甲基甲酰胺和二甲基亚砜溶解原料时,只有N,N-二甲基甲酰胺、二甲基亚砜对Anisiflupurin、赤霉酸GA3的溶解效果最好。It can be seen from Table 3 that when using the same quality of absolute ethanol, cyclohexanone, propylene glycol methyl ether acetate, N,N-dimethylformamide and dimethyl sulfoxide to dissolve the raw materials, only N,N-dimethyl Formamide and dimethyl sulfoxide have the best dissolving effect on Anisiflupurin and gibberellic acid GA3.
为了考察稳定剂对液体制剂的影响,按照实施例1的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表4所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 1. The liquid preparations, the type of stabilizer and the dilution stability of each liquid preparation prepared are shown in Table 4.
表4稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 4 Types of stabilizers and dilution stability of each prepared liquid formulation
由表4可知,选用甲酸作为稳定剂时,制剂的稀释稳定性合格;选用甲酸铝、甲酸镁、柠檬酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 4 that when formic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when aluminum formate, magnesium formate, and citric acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation, which is unqualified.
当将表4中的助溶剂由二甲基亚砜替换为N,N-二甲基甲酰胺时或者将乳化剂由辛基酚聚氧乙烯醚替换为吐温80时,稀释稳定性的测试结果均为不合格。Test of dilution stability when the co-solvent in Table 4 is replaced from dimethyl sulfoxide to N,N-dimethylformamide or the emulsifier is replaced from octylphenol polyoxyethylene ether to Tween 80 The results were all unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例1的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤0.9%,赤霉酸GA3的质量分数≤0.9%,助溶剂的质量分数为15~25%,稳定剂的质量分数为0.5~2%,乳化剂的质量分数为1~4%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method was as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 1 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤0.9%, the mass fraction of gibberellic acid GA3 is ≤0.9%, and the mass fraction of the cosolvent is 15~ 25%, the mass fraction of stabilizer is 0.5-2%, the mass fraction of emulsifier is 1-4%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids, and the pH value is 2-5. The test results of long-lasting foaming, dilution stability, low temperature stability and thermal storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例2Example 2
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、赤霉酸、稳定剂、乳化剂、溶剂和助溶剂组成;赤霉酸、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表5所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H -Purine-6-amine (Anisiflupurin), gibberellic acid, stabilizer, emulsifier, solvent and co-solvent composition; types of gibberellic acid, stabilizer, emulsifier, solvent and co-solvent and the mass fraction of each component such as As shown in Table 5.
表5实施例2的液体制剂中赤霉酸、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 5 Types of gibberellic acid, stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 2 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为40转/min,边搅拌边加入Anisiflupurin、赤霉酸,加入完毕后,再搅拌60min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌30min,最后再加入溶剂,继续搅拌60min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 40 rpm. Add Anisiflupurin and gibberellic acid while stirring. After the addition is completed, stir for another 60 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add stabilizer, emulsifier, continue stirring for 30 minutes, finally add the solvent, continue stirring for 60 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、赤霉酸完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing the liquid preparation, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and gibberellic acid, the stirring time is controlled to 30-60 min; after adding the stabilizer and emulsifier, the stirring time is controlled is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、赤霉酸的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表6所示。The liquid preparation of this example was tested for Anisiflupurin and gibberellic acid content, pH value, long-lasting foaming property, dilution stability, low temperature stability and thermal storage stability. The results are shown in Table 6.
表6实施例2的液体制剂的性能测试结果Table 6 Performance test results of the liquid formulation of Example 2
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入35g的助溶剂,准确称取Anisiflupurin 1.8g、赤霉酸GA4+7 1.8g,在转速为40转/min的条件下,搅拌溶解60min,观察Anisiflupurin、赤霉酸GA4+7的溶解情况,结果如表7所示。In order to examine the impact of different co-solvents on liquid preparations, add 35 g of co-solvents to the mixing device, accurately weigh 1.8 g of Anisiflupurin and 1.8 g of gibberellic acid GA4+7, and stir at a speed of 40 rpm. Dissolve for 60 minutes and observe the dissolution of Anisiflupurin and gibberellic acid GA4+7. The results are shown in Table 7.
表7不同助溶剂对Anisiflupurin、赤霉酸GA4+7的溶解情况Table 7 Dissolution of Anisiflupurin and gibberellic acid GA4+7 by different co-solvents
由表7可知,使用相同质量的磷酸三甲酯、一乙醇胺、甲基异丁基酮、N-甲基吡咯烷酮和N,N-二甲基甲酰胺溶解原料时,只有N-甲基吡咯烷酮和N,N-二甲基甲酰胺对Anisiflupurin、赤霉酸GA4+7的溶解效果最好。It can be seen from Table 7 that when the same mass of trimethyl phosphate, monoethanolamine, methyl isobutyl ketone, N-methylpyrrolidone and N,N-dimethylformamide is used to dissolve the raw materials, only N-methylpyrrolidone and N,N-dimethylformamide has the best dissolving effect on Anisiflupurin and gibberellic acid GA4+7.
为了考察稳定剂对液体制剂的影响,按照实施例2的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表8所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 2. The liquid preparations, the types of stabilizers and the dilution stability of each liquid preparation prepared are shown in Table 8.
表8稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 8 Types of stabilizers and dilution stability of each liquid formulation produced
由表8可知,选用乳酸作为稳定剂时,制剂的稀释稳定性合格;选用硫酸铝、硫酸铁、苹果酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 8 that when lactic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when aluminum sulfate, iron sulfate, and malic acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation, which is unqualified.
当将表8中的助溶剂由N,N-二甲基甲酰胺替换为N-甲基吡咯烷酮时或者将乳化剂由脂肪醇聚氧乙烯醚替换为吐温80时,稀释稳定性的测试结果均为不合格。When the co-solvent in Table 8 is replaced from N,N-dimethylformamide to N-methylpyrrolidone or the emulsifier is replaced from fatty alcohol polyoxyethylene ether to Tween 80, the test results of dilution stability All are unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例2的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤1.8%,赤霉酸GA4+7的质量分数≤1.8%,助溶剂的质量分数为30~40%,稳定剂的质量分数为10~20%,乳化剂的质量分数为2~4%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method was as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 2 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤1.8%, the mass fraction of gibberellic acid GA4+7 is ≤1.8%, the mass fraction of the cosolvent is When the mass fraction of stabilizer is 30 to 40%, the mass fraction of stabilizer is 10 to 20%, the mass fraction of emulsifier is 2 to 4%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids with a pH value of 2 to 5. The test results of long-lasting foaming, dilution stability, low temperature stability and heat storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例3Example 3
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂组成;芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表9所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H - Purine-6-amine (Anisiflupurin), brassinolide, stabilizer, emulsifier, solvent and co-solvent composition; types and components of brassinolide, stabilizer, emulsifier, solvent and co-solvent The quality scores are shown in Table 9.
表9实施例3的液体制剂中芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 9 Types of brassinolides, stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 3 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为80转/min,边搅拌边加入Anisiflupurin、芸苔素内酯,加入完毕后,再搅拌30min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌60min,最后再加入溶剂,继续搅拌30min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 80 rpm. Add Anisiflupurin and brassinolide while stirring. After the addition is completed, stir for another 30 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved; then add in order to stabilize agent and emulsifier, continue stirring for 60 minutes, finally add solvent, continue stirring for 30 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、芸苔素内酯完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing liquid preparations, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and brassinolide, the stirring time is controlled to 30-60 min; after adding stabilizers and emulsifiers, controlling The stirring time is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、芸苔素内酯的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表10所示。The liquid preparation of this example was tested for the content of Anisiflupurin and brassinolide, pH value, long-lasting foaming property, dilution stability, low temperature stability and heat storage stability. The results are shown in Table 10.
表10实施例3的液体制剂的性能测试结果Table 10 Performance test results of the liquid formulation of Example 3
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入15g的助溶剂,准确称取Anisiflupurin 1.99g、24-表芸苔素内酯0.01g,在转速为80转/min的条件下,搅拌溶解30min,观察Anisiflupurin、24-表芸苔素内酯的溶解情况,结果如表11所示。In order to examine the impact of different co-solvents on liquid preparations, add 15 g of co-solvents to the mixing device, accurately weigh 1.99 g of Anisiflupurin and 0.01 g of 24-epibrassinolide at a speed of 80 rpm. , stir and dissolve for 30 minutes, and observe the dissolution of Anisiflupurin and 24-epibrassinolide. The results are shown in Table 11.
表11不同助溶剂对Anisiflupurin、24-表芸苔素内酯的溶解情况Table 11 Dissolution of Anisiflupurin and 24-epibrassinolide by different cosolvents
由表11可知,使用相同质量的三乙醇胺、正丁醚、乙酸乙酯、乙二醇和N-甲基吡咯烷酮溶解原料时,只有乙二醇和N-甲基吡咯烷酮对Anisiflupurin、24-表芸苔素内酯的溶解效果最好。It can be seen from Table 11 that when the same quality of triethanolamine, n-butyl ether, ethyl acetate, ethylene glycol and N-methylpyrrolidone are used to dissolve the raw materials, only ethylene glycol and N-methylpyrrolidone have significant effects on Anisiflupurin and 24-epibrassinoline. Lactone has the best dissolving effect.
为了考察稳定剂对液体制剂的影响,按照实施例3的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表12所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 3. The liquid preparations, the types of stabilizers and the dilution stability of each liquid preparation prepared are shown in Table 12.
表12稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 12 Types of stabilizers and dilution stability of each liquid formulation produced
由表12可知,选用冰醋酸作为稳定剂时,制剂的稀释稳定性合格;选用氨水、0.1mol/L的NaOH水溶液、酒石酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 12 that when glacial acetic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when ammonia water, 0.1 mol/L NaOH aqueous solution, and tartaric acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation , unqualified.
当将表12中的助溶剂由N-甲基吡咯烷酮替换为乙二醇时或者将乳化剂由吐温80替换为司盘60时,稀释稳定性的测试结果均为不合格。When the co-solvent in Table 12 is replaced from N-methylpyrrolidone to ethylene glycol or the emulsifier is replaced from Tween 80 to Span 60, the dilution stability test results are unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例3的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤1.99%,24-高芸苔素内酯的质量分数≤0.01%,助溶剂的质量分数为10~20%,稳定剂的质量分数为3~6%,乳化剂的质量分数为3~7%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method is as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 3 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤1.99%, the mass fraction of 24-homobrassinolide is ≤0.01%, and the mass fraction of the cosolvent is When the mass fraction of the stabilizer is 3 to 6%, the mass fraction of the emulsifier is 3 to 7%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids with a pH value of 2 to 20%. 5. The test results of long-lasting foaming, dilution stability, low temperature stability and heat storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例4Example 4
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂组成;芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表13所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H - Purine-6-amine (Anisiflupurin), brassinolide, stabilizer, emulsifier, solvent and co-solvent composition; types and components of brassinolide, stabilizer, emulsifier, solvent and co-solvent The quality scores are shown in Table 13.
表13实施例4的液体制剂中芸苔素内酯、稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 13 Types of brassinolides, stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 4 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为40转/min,边搅拌边加入Anisiflupurin、芸苔素内酯,加入完毕后,再搅拌60min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌30min,最后再加入溶剂,继续搅拌60min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 40 rpm. Add Anisiflupurin and brassinolide while stirring. After the addition is completed, stir for another 60 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add in order to stabilize the reaction. agent and emulsifier, continue stirring for 30 minutes, finally add solvent, continue stirring for 60 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、芸苔素内酯完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing liquid preparations, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and brassinolide, the stirring time is controlled to 30-60 min; after adding stabilizers and emulsifiers, controlling The stirring time is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、芸苔素内酯的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表14所示。The liquid preparation of this example was tested for the content of Anisiflupurin and brassinolide, pH value, long-lasting foaming property, dilution stability, low temperature stability and heat storage stability. The results are shown in Table 14.
表14实施例4的液体制剂的性能测试结果Table 14 Performance test results of the liquid formulation of Example 4
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入30g的助溶剂,准确称取Anisiflupurin 4.995g、28-高芸苔素内酯0.005g,在转速为40转/min的条件下,搅拌溶解60min,观察Anisiflupurin、28-高芸苔素内酯的溶解情况,结果如表15所示。In order to examine the impact of different co-solvents on liquid preparations, add 30 g of co-solvents to the mixing device, accurately weigh 4.995 g of Anisiflupurin and 0.005 g of 28-homobrastisolide, and stir at a speed of 40 rpm. Dissolve for 60 minutes and observe the dissolution of Anisiflupurin and 28-homobrassinolide. The results are shown in Table 15.
表15不同助溶剂对Anisiflupurin、28-高芸苔素内酯的溶解情况Table 15 Dissolution of Anisiflupurin and 28-Homobrassinolide by different co-solvents
由表15可知,使用相同质量的无水乙醇、正丁醇、乙酸乙酯、丙二醇和二甲基亚砜溶解原料时,只有丙二醇和二甲基亚砜对Anisiflupurin、28-高芸苔素内酯的溶解效果最好。It can be seen from Table 15 that when the same quality of absolute ethanol, n-butanol, ethyl acetate, propylene glycol and dimethyl sulfoxide are used to dissolve the raw materials, only propylene glycol and dimethyl sulfoxide have an effective effect on Anisiflupurin and 28-homobrassinolide. Dissolving effect is the best.
为了考察稳定剂对液体制剂的影响,按照实施例4的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表16所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 4. The liquid preparations, the type of stabilizer and the dilution stability of each liquid preparation prepared are shown in Table 16.
表16稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 16 Types of stabilizers and dilution stability of each liquid formulation produced
由表16可知,选用甲酸作为稳定剂时,制剂的稀释稳定性合格;选用甲酸铝、甲酸镁、丙酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 16 that when formic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when aluminum formate, magnesium formate, and propionic acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation, which is unqualified.
当将表16中的助溶剂由二甲基亚砜替换为丙二醇时或者将乳化剂由聚乙二醇400替换为司盘80时,稀释稳定性的测试结果均为不合格。When the co-solvent in Table 16 is replaced from dimethyl sulfoxide to propylene glycol or the emulsifier is replaced from polyethylene glycol 400 to Span 80, the dilution stability test results are unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例4的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤4.995%,28-高芸苔素内酯的质量分数≤0.005%,助溶剂的质量分数为20~40%,稳定剂的质量分数为0.3~0.6%,乳化剂的质量分数为4~8%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the impact of the dosage of each component on the liquid preparation was examined. The specific method was as follows: Liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 4 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤4.995%, the mass fraction of 28-homobrassinolide is ≤0.005%, and the mass fraction of the cosolvent is 20-40%, the mass fraction of stabilizer is 0.3-0.6%, the mass fraction of emulsifier is 4-8%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids, and the pH value is 2- 5. The test results of long-lasting foaming, dilution stability, low temperature stability and heat storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例5Example 5
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、胺鲜酯、稳定剂、乳化剂、溶剂和助溶剂组成;稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表17所示。表17中的EO/PO嵌段聚醚的生产厂家为南京捷润科技有限公司,产品型号为Ethylan NS-500LQ,EO/PO嵌段聚醚中的EO/PO的摩尔比例为1:1.71。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H -Purine-6-amine (Anisiflupurin), ethanol, stabilizer, emulsifier, solvent and co-solvent; the types of stabilizer, emulsifier, solvent and co-solvent and the mass fraction of each component are shown in Table 17 . The manufacturer of the EO/PO block polyether in Table 17 is Nanjing Jierun Technology Co., Ltd., and the product model is Ethylan NS-500LQ. The molar ratio of EO/PO in the EO/PO block polyether is 1:1.71.
表17实施例5的液体制剂中稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 17 Types of stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 5 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为80转/min,边搅拌边加入Anisiflupurin、胺鲜酯,加入完毕后,再搅拌30min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌60min,最后再加入溶剂,继续搅拌30min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 80 rpm. While stirring, add Anisiflupurin and ampicillin. After the addition is completed, stir for another 30 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add stabilizer, emulsifier, continue stirring for 60 minutes, finally add the solvent, continue stirring for 30 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、胺鲜酯完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing liquid preparations, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and ethanol, the stirring time is controlled to 30-60 min; after adding stabilizers and emulsifiers, the stirring time is controlled is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、胺鲜酯的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表18所示。The liquid preparation of this example was tested for Anisiflupurin and ethanol content, pH value, long-lasting foaming property, dilution stability, low temperature stability and thermal storage stability. The results are shown in Table 18.
表18实施例5的液体制剂的性能测试结果Table 18 Performance test results of the liquid formulation of Example 5
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入15g的助溶剂,准确称取Anisiflupurin 2.00g、胺鲜酯8.00g,在转速为80转/min的条件下,搅拌溶解30min,观察Anisiflupurin、胺鲜酯的溶解情况,结果如表19所示。In order to examine the impact of different co-solvents on liquid preparations, add 15 g of co-solvents to the mixing device, accurately weigh 2.00 g of Anisiflupurin and 8.00 g of ethyl glycosides, and stir and dissolve for 30 minutes at a speed of 80 rpm. Observe the dissolution of Anisiflupurin and ethanol. The results are shown in Table 19.
表19不同助溶剂对Anisiflupurin、胺鲜酯的溶解情况Table 19 The dissolution of Anisiflupurin and ethanol by different cosolvents
由表19可知,使用相同质量的磷酸三甲酯、一乙醇胺、甲基异丁基酮、乙二醇和N-甲基吡咯烷酮溶解原料时,只有乙二醇和N-甲基吡咯烷酮对Anisiflupurin、胺鲜酯的溶解效果最好。It can be seen from Table 19 that when the same quality of trimethyl phosphate, monoethanolamine, methyl isobutyl ketone, ethylene glycol and N-methylpyrrolidone are used to dissolve the raw materials, only ethylene glycol and N-methylpyrrolidone have significant effects on Anisiflupurin and amines. Ester dissolves best.
为了考察稳定剂对液体制剂的影响,按照实施例5的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表20所示。表20中的BHT代表2,6-二叔丁基对甲酚,TBHQ代表叔丁基对苯二酚,EO/PO嵌段聚醚的生产厂家为南京捷润科技有限公司,产品型号为Ethylan NS-500LQ。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 5. The liquid preparations, the type of stabilizer and the dilution stability of each liquid preparation prepared are shown in Table 20. BHT in Table 20 represents 2,6-di-tert-butyl-p-cresol, TBHQ represents tert-butylhydroquinone, the manufacturer of EO/PO block polyether is Nanjing Jierun Technology Co., Ltd., and the product model is Ethylan NS-500LQ.
表20稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 20 Types of stabilizers and dilution stability of each liquid formulation produced
由表20可知,选用BHT或者TBHQ作为稳定剂时,制剂的稀释稳定性合格;选用硫酸铁、氨水、茶多酚作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 20 that when BHT or TBHQ is used as the stabilizer, the dilution stability of the preparation is qualified; when iron sulfate, ammonia water, and tea polyphenols are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation. qualified.
当将表20中的助溶剂由N-甲基吡咯烷酮替换为乙二醇时或者将乳化剂由EO/PO嵌段聚醚替换为吐温80时,稀释稳定性的测试结果均为不合格。When the co-solvent in Table 20 is replaced from N-methylpyrrolidone to ethylene glycol or the emulsifier is replaced from EO/PO block polyether to Tween 80, the test results for dilution stability are all unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例5的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤2%,胺鲜酯的质量分数≤8%,助溶剂的质量分数为20~30%,稳定剂的质量分数为1~3%,乳化剂的质量分数为0.5~2%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the impact of the dosage of each component on the liquid preparation was examined. The specific method was as follows: Liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 5 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤ 2%, the mass fraction of ethanol is ≤ 8%, and the mass fraction of the cosolvent is 20 to 30 %, the mass fraction of stabilizer is 1 to 3%, the mass fraction of emulsifier is 0.5 to 2%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids with a pH value of 2 to 5 and are long-lasting. The test results of foaming property, dilution stability, low temperature stability and thermal storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例6Example 6
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由以下质量分数的组分组成:由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、乙烯利、乳化剂、溶剂和助溶剂组成;乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表21所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is composed of the following mass fraction components: 2-fluoro-N-(3 -Methoxyphenyl)-7H-purin-6-amine (Anisiflupurin), ethephon, emulsifier, solvent and co-solvent; the types of emulsifier, solvent and co-solvent and the mass fraction of each component are shown in Table 21 shown.
表21实施例6的液体制剂中乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 21 Types of emulsifiers, solvents and co-solvents in the liquid preparation of Example 6 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为80转/min,边搅拌边加入Anisiflupurin、乙烯利,加入完毕后,再搅拌30min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入乳化剂,继续搅拌60min,最后再加入溶剂,继续搅拌30min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 80 rpm. Add Anisiflupurin and Ethephon while stirring. After the addition is completed, stir for another 30 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution is achieved. Add emulsifier in turn and continue. Stir for 60 minutes, finally add the solvent, and continue stirring for 30 minutes to obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、乙烯利完毕后,控制搅拌时间为30-60min;加入乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing the liquid preparation, the stirring speed is controlled to 40-80 rpm; after adding Anisiflupurin and ethephon, the stirring time is controlled to 30-60min; after the emulsifier is added, the stirring time is controlled to 30-60min ; After adding the solvent, control the stirring time to 30-60 minutes.
对本实施例的液体制剂进行Anisiflupurin、乙烯利的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表22所示。The liquid preparation of this example was tested for Anisiflupurin, ethephon content, pH value, persistent foaming property, dilution stability, low temperature stability and thermal storage stability. The results are shown in Table 22.
表22实施例6的液体制剂的性能测试结果Table 22 Performance test results of the liquid formulation of Example 6
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入35g的助溶剂,准确称取Anisiflupurin 0.5g、乙烯利29.5g,在转速为80转/min的条件下,搅拌溶解30min,观察Anisiflupurin、乙烯利的溶解情况,结果如表23所示。In order to examine the influence of different cosolvents on liquid preparations, add 35g of cosolvents to the mixing device, accurately weigh 0.5g of Anisiflupurin and 29.5g of ethephon, stir and dissolve for 30 minutes at a speed of 80 rpm, and observe The results of the dissolution of Anisiflupurin and ethephon are shown in Table 23.
表23不同助溶剂对Anisiflupurin、乙烯利的溶解情况Table 23 Dissolution of Anisiflupurin and Ethephon by different co-solvents
由表23可知,使用相同质量的无水乙醇、正丁醇、乙酸乙酯、丙酸和乳酸溶解原料时,只有丙酸、乳酸对Anisiflupurin、乙烯利的溶解效果最好。It can be seen from Table 23 that when the same quality of absolute ethanol, n-butanol, ethyl acetate, propionic acid and lactic acid are used to dissolve the raw materials, only propionic acid and lactic acid have the best dissolving effect on Anisiflupurin and ethephon.
为了考察溶剂对液体制剂的影响,按照实施例6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同溶剂的液体制剂,溶剂的类型以及制得的各液体制剂的稀释稳定性如表24所示。In order to examine the influence of solvents on liquid preparations, liquids containing different solvents were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 6. The formulation, type of solvent, and dilution stability of each liquid formulation produced are shown in Table 24.
表24溶剂的类型以及制得的各液体制剂的稀释稳定性Table 24 Types of solvents and dilution stability of each prepared liquid formulation
由表24可知,选用乙二醇、丙二醇、去离子水作为溶剂时,制剂的稀释稳定性均合格;但是去离子水的成本更低。It can be seen from Table 24 that when ethylene glycol, propylene glycol, and deionized water are used as solvents, the dilution stability of the preparations is qualified; however, the cost of deionized water is lower.
当将表24中的助溶剂由乳酸替换为丙酸时或者将乳化剂由聚乙二醇400替换为吐温80时,稀释稳定性的测试结果均为不合格。When the cosolvent in Table 24 is replaced from lactic acid to propionic acid or the emulsifier is replaced from polyethylene glycol 400 to Tween 80, the test results for dilution stability are all unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤0.5%,乙烯利的质量分数≤29.5%,助溶剂的质量分数为30~40%,乳化剂的质量分数为3~6%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method is as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 6 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤0.5%, the mass fraction of ethephon is ≤29.5%, and the mass fraction of the cosolvent is 30 to 40%. , when the mass fraction of emulsifier is 3 to 6%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids, with a pH value of 2 to 5, with long-lasting foaming properties, dilution stability, low temperature stability and The test results of thermal storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例7Example 7
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、三十烷醇、稳定剂、乳化剂、溶剂和助溶剂组成;稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表25所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is prepared from 2-fluoro-N-(3-methoxyphenyl)-7H - Purine-6-amine (Anisiflupurin), triacontanol, stabilizer, emulsifier, solvent and co-solvent; the types of stabilizer, emulsifier, solvent and co-solvent and the mass fraction of each component are shown in Table 25 Show.
表25实施例7的液体制剂中稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 25 Types of stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 7 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为80转/min,边搅拌边加入Anisiflupurin、三十烷醇,加入完毕后,再搅拌30min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌60min,最后再加入溶剂,继续搅拌30min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 80 rpm. Add Anisiflupurin and triacontanol while stirring. After the addition is completed, stir for another 30 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add the stabilizer in turn. , emulsifier, continue stirring for 60 minutes, finally add the solvent, continue stirring for 30 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、三十烷醇完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing liquid preparations, control the stirring speed to 40-80 rpm; after adding Anisiflupurin and triacontanol, control the stirring time to 30-60 min; after adding stabilizers and emulsifiers, control stirring The time is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、三十烷醇的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表26所示。The liquid preparation of this example was tested for Anisiflupurin and triacontanol content, pH value, long-lasting foaming property, dilution stability, low temperature stability and thermal storage stability. The results are shown in Table 26.
表26实施例7的液体制剂的性能测试结果Table 26 Performance test results of the liquid formulation of Example 7
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入15g的助溶剂,准确称取Anisiflupurin 1.9g、三十烷醇0.1g,在转速为80转/min的条件下,搅拌溶解30min,观察Anisiflupurin、三十烷醇的溶解情况,结果如表27所示。In order to examine the impact of different co-solvents on liquid preparations, add 15 g of co-solvents to the mixing device, accurately weigh 1.9 g of Anisiflupurin and 0.1 g of triacontanol, and stir and dissolve for 30 minutes at a speed of 80 rpm. , observe the dissolution of Anisiflupurin and triacontanol, and the results are shown in Table 27.
表27不同助溶剂对Anisiflupurin、三十烷醇的溶解情况Table 27 Dissolution of Anisiflupurin and triacontanol by different cosolvents
由表27可知,使用相同质量的磷酸三甲酯、一乙醇胺、甲基异丁基酮、乙二醇和二甲基亚砜溶解原料时,只有乙二醇和二甲基亚砜对Anisiflupurin、三十烷醇的溶解效果最好。It can be seen from Table 27 that when the same quality of trimethyl phosphate, monoethanolamine, methyl isobutyl ketone, ethylene glycol and dimethyl sulfoxide are used to dissolve the raw materials, only ethylene glycol and dimethyl sulfoxide have significant effects on Anisiflupurin, 30 Alkanols have the best dissolving effect.
为了考察稳定剂对液体制剂的影响,按照实施例7的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表28所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 7. The liquid preparations, the type of stabilizer and the dilution stability of each liquid preparation prepared are shown in Table 28.
表28稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 28 Types of stabilizers and dilution stability of each liquid formulation produced
由表28可知,选用冰醋酸作为稳定剂时,制剂的稀释稳定性合格;选用硫酸铁、氨水、乳酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 28 that when glacial acetic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when iron sulfate, ammonia water, and lactic acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation, which is unqualified.
当将表28中的助溶剂由二甲基亚砜替换为乙二醇时或者将乳化剂由脂肪醇聚氧乙烯醚替换为辛基酚聚氧乙烯醚时,稀释稳定性的测试结果均为不合格。When the cosolvent in Table 28 is replaced from dimethyl sulfoxide to ethylene glycol or the emulsifier is replaced from fatty alcohol polyoxyethylene ether to octylphenol polyoxyethylene ether, the test results of dilution stability are all Unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例7的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数≤1.9%,三十烷醇的质量分数≤0.1%,助溶剂的质量分数为10~20%,稳定剂的质量分数为1~3%,乳化剂的质量分数为2~6%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method is as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 7 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is ≤1.9%, the mass fraction of triacontanol is ≤0.1%, and the mass fraction of the cosolvent is 10~ 20%, the mass fraction of stabilizer is 1 to 3%, the mass fraction of emulsifier is 2 to 6%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids, and the pH value is 2 to 5. The test results of long-lasting foaming, dilution stability, low temperature stability and thermal storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
实施例8Example 8
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂,由以下质量分数的组分组成:由2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺(Anisiflupurin)、三十烷醇、稳定剂、乳化剂、溶剂和助溶剂组成;稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数如表29所示。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this embodiment is composed of the following mass fraction components: 2-fluoro-N-(3 -Methoxyphenyl)-7H-purin-6-amine (Anisiflupurin), triacontanol, stabilizer, emulsifier, solvent and co-solvent composition; types of stabilizers, emulsifiers, solvents and co-solvents and their respective The mass fractions of the components are shown in Table 29.
表29实施例8的液体制剂中稳定剂、乳化剂、溶剂和助溶剂的类型以及各组分的质量分数Table 29 Types of stabilizers, emulsifiers, solvents and co-solvents in the liquid preparation of Example 8 and the mass fraction of each component
本实施例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法,具体包括以下步骤:先用隔膜泵将助溶剂抽入反应釜中,开启搅拌,搅拌转速为40转/min,边搅拌边加入Anisiflupurin、三十烷醇,加入完毕后,再搅拌60min,反应釜中无可见溶质颗粒,达到完全溶解;再依次加入稳定剂、乳化剂,继续搅拌30min,最后再加入溶剂,继续搅拌60min,得到含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂。The preparation method of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purine-6-amine in this embodiment specifically includes the following steps: first use a diaphragm pump to pump the co-solvent into the reaction In the kettle, start stirring at a stirring speed of 40 rpm. Add Anisiflupurin and triacontanol while stirring. After the addition is complete, stir for another 60 minutes. There will be no visible solute particles in the reaction kettle and complete dissolution will be achieved. Then add the stabilizer in turn. , emulsifier, continue stirring for 30 minutes, finally add the solvent, continue stirring for 60 minutes, and obtain a liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine.
在其他实施例中,制备液体制剂时,控制搅拌转速为40-80转/min;加入Anisiflupurin、三十烷醇完毕后,控制搅拌时间为30-60min;加入稳定剂、乳化剂后,控制搅拌时间为30-60min;加入溶剂后,控制搅拌时间为30-60min。In other embodiments, when preparing liquid preparations, control the stirring speed to 40-80 rpm; after adding Anisiflupurin and triacontanol, control the stirring time to 30-60 min; after adding stabilizers and emulsifiers, control stirring The time is 30-60min; after adding the solvent, control the stirring time to 30-60min.
对本实施例的液体制剂进行Anisiflupurin、三十烷醇的含量、pH值、持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试,结果如表30所示。The liquid preparation of this example was tested for Anisiflupurin and triacontanol content, pH value, long-lasting foaming property, dilution stability, low temperature stability and heat storage stability. The results are shown in Table 30.
表30实施例8的液体制剂的性能测试结果Table 30 Performance test results of the liquid formulation of Example 8
为了考察不同助溶剂对液体制剂的影响,在混合装置中,加入35g的助溶剂,准确称取Anisiflupurin 9.8g、三十烷醇0.2g,在转速为40转/min的条件下,搅拌溶解60min,观察Anisiflupurin、三十烷醇的溶解情况,结果如表31所示。In order to examine the impact of different co-solvents on liquid preparations, add 35 g of co-solvents to the mixing device, accurately weigh 9.8 g of Anisiflupurin and 0.2 g of triacontanol, and stir and dissolve for 60 minutes at a speed of 40 rpm. , observe the dissolution of Anisiflupurin and triacontanol, and the results are shown in Table 31.
表31不同助溶剂对Anisiflupurin、三十烷醇的溶解情况Table 31 Dissolution of Anisiflupurin and Triacontanol by different cosolvents
由表31可知,使用相同质量的正丁醇、三乙醇胺、碳酸丙烯酯、丙二醇和N-甲基吡咯烷酮溶解原料时,只有丙二醇和N-甲基吡咯烷酮对Anisiflupurin、三十烷醇的溶解效果最好。It can be seen from Table 31 that when using the same mass of n-butanol, triethanolamine, propylene carbonate, propylene glycol and N-methylpyrrolidone to dissolve the raw materials, only propylene glycol and N-methylpyrrolidone have the best dissolving effect on Anisiflupurin and triacontanol. good.
为了考察稳定剂对液体制剂的影响,按照实施例8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备含有不同稳定剂的液体制剂,稳定剂的类型以及制得的各液体制剂的稀释稳定性如表32所示。In order to examine the impact of stabilizers on liquid preparations, liquid preparations containing different stabilizers were prepared according to the preparation method of liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 8. The liquid preparations, the type of stabilizer and the dilution stability of each liquid preparation prepared are shown in Table 32.
表32稳定剂的类型以及制得的各液体制剂的稀释稳定性Table 32 Types of stabilizers and dilution stability of each liquid formulation produced
由表32可知,选用甲酸作为稳定剂时,制剂的稀释稳定性合格;选用甲酸铝、甲酸镁、苹果酸作为稳定剂时,测试稀释稳定性时,液体制剂的底部均出现沉淀,不合格。It can be seen from Table 32 that when formic acid is used as the stabilizer, the dilution stability of the preparation is qualified; when aluminum formate, magnesium formate, and malic acid are used as the stabilizer, when the dilution stability is tested, precipitation appears at the bottom of the liquid preparation, which is unqualified.
当将表32中的助溶剂由N-甲基吡咯烷酮替换为丙二醇时或者将乳化剂由吐温80替换为司盘80时,稀释稳定性的测试结果均为不合格。When the co-solvent in Table 32 is replaced from N-methylpyrrolidone to propylene glycol or the emulsifier is replaced from Tween 80 to Span 80, the dilution stability test results are unqualified.
最后,考察了各组分的用量对液体制剂的影响,具体方法如下:按照实施例8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的制备方法制备液体制剂,区别在于,改变各组分的质量分数,结果表明,当Anisiflupurin的质量分数>1.9%且≤9.8%,三十烷醇的质量分数>0.1%且≤0.2%,助溶剂的质量分数为30~40%,稳定剂的质量分数为6~10%,乳化剂的质量分数为3~7%,余量为溶剂时,制得的液体制剂均为澄清透明液体,且pH值为2~5,持久起泡性、稀释稳定性、低温稳定性和热贮稳定性的测试结果均合格。当组成液体制剂中的某一组分的质量分数不在上述数值范围内时,制得的液体制剂的性能指标中有一项或多项不满足要求。Finally, the influence of the dosage of each component on the liquid preparation was examined. The specific method is as follows: liquid containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine according to Example 8 The preparation method of the preparation is to prepare a liquid preparation. The difference is that the mass fraction of each component is changed. The results show that when the mass fraction of Anisiflupurin is > 1.9% and ≤ 9.8%, the mass fraction of triacontanol is > 0.1% and ≤ 0.2%. When the mass fraction of co-solvent is 30-40%, the mass fraction of stabilizer is 6-10%, the mass fraction of emulsifier is 3-7%, and the balance is solvent, the liquid preparations prepared are all clear and transparent liquids. The pH value is 2 to 5, and the test results of long-lasting foaming, dilution stability, low-temperature stability and thermal storage stability are all qualified. When the mass fraction of a certain component in the liquid preparation is not within the above numerical range, one or more of the performance indicators of the prepared liquid preparation do not meet the requirements.
对比例1Comparative example 1
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例1的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的赤霉酸GA3的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 1. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of gibberellic acid GA3 is 0.
对比例2Comparative example 2
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例2的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的赤霉酸GA4+7的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 2. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of gibberellic acid GA4+7 is 0.
对比例3Comparative example 3
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例3的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的24-表芸苔素内酯的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 3. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of 24-epibrassinolide is 0.
对比例4Comparative example 4
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例4的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的28-高芸苔素内酯的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 4. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of 28-homobrassinolide is 0.
对比例5Comparative example 5
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例5的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的胺鲜酯的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 5. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of ethylamine is 0.
对比例6Comparative example 6
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的乙烯利的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl) in Example 6. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of ethephon is 0.
对比例7Comparative example 7
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例5的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 5. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine is 0.
对比例8Comparative example 8
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl) in Example 6. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine is 0.
对比例9Comparative example 9
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例7的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的三十烷醇的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Example 7. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of triacontanol is 0.
对比例10Comparative example 10
本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂与实施例8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂的区别仅在于,本对比例的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂中的三十烷醇的质量分数为0。The liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is different from the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl) in Example 8. The only difference between the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in this comparative example is that The mass fraction of triacontanol is 0.
实验例1Experimental example 1
为了评价实施例1和实施例2的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对燕麦胚芽鞘生长的影响,以市售4%赤霉酸可溶液剂(郑州郑氏化工产品有限公司生产)作为对照药剂,同时以清水作为空白对照,然后将不同制剂采用清水稀释,得到测试试剂。然后测试各测试试剂对燕麦胚芽鞘生长的影响,测试方法如下:在黑暗条件下培养燕麦,待燕麦苗长至5cm左右时,从燕麦苗上剪取芽鞘,然后切掉芽鞘的顶端(切掉的长度为6mm),得到去除顶端的芽鞘,再用定量剪切刀在去除顶端的芽鞘的最上端向下统一切取长度为1cm的切段,得到芽鞘切段。然后将芽鞘切段浸泡在含2%(质量分数)蔗糖的磷酸-柠檬酸缓冲液(pH=5.0)中3h,洗去内源生长素。然后取洗净烘干的培养皿,每个培养皿中放入10个洗去内源生长素的芽鞘切段,再向每个培养皿中加入同一测试试剂(体积均为20mL),使培养皿中的芽鞘切段浸泡在测试试剂中,同时每种测试试剂设置5个平行实验(即每种测试试剂对应加入的培养皿的个数均为5),然后将加入有测试试剂和芽鞘切段的培养皿放置在摇床中于黑暗条件下培养24h或48h,培养结束后,测试每个培养皿中的每个芽鞘切段的生长量,然后计算每一种测试试剂对应的5个培养皿中的所有芽鞘切段的生长量的平均值,以计算得到的平均值作为相应测试试剂对应的芽鞘切段生长量的测试结果,将采用清水作为测试试剂对应的芽鞘切段生长量的测试结果定义为M,然后计算各测试试剂对应的胚芽鞘促长率,计算公式为:胚芽鞘促长率(%)=(芽鞘切段的生长量的测试结果-M)/M×100。各测试试剂的编号、各测试试剂中的有效成分(2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺、赤霉酸GA3和赤霉酸GA4+7)的浓度以及各测试试剂在不同培养时间时对应的胚芽鞘促长率如表33所示。In order to evaluate the effect of the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of Examples 1 and 2 on the growth of oat coleoptiles, commercially available 4% Gibberellic acid soluble agent (produced by Zhengzhou Zhengshi Chemical Products Co., Ltd.) was used as a control agent, and water was used as a blank control. Then different preparations were diluted with water to obtain test reagents. Then test the effect of each test reagent on the growth of oat coleoptiles. The test method is as follows: Cultivate oats under dark conditions. When the oat seedlings grow to about 5cm, cut the coleoptiles from the oat seedlings, and then cut off the top of the coleoptiles ( The cut length is 6mm) to obtain the bud sheath with the top removed, and then use a quantitative scissor to uniformly cut 1 cm length from the uppermost end of the bud sheath with the top removed to obtain the bud sheath segments. Then, the cut sections of the coleoptiles were soaked in phosphate-citric acid buffer (pH=5.0) containing 2% (mass fraction) sucrose for 3 hours to wash away the endogenous auxin. Then take the washed and dried petri dishes, put 10 cut sections of bud sheaths that have been washed away of endogenous auxin into each petri dish, and then add the same test reagent (the volume is 20mL) to each petri dish, so that The cut sections of bud sheaths in the petri dish are soaked in the test reagents. At the same time, five parallel experiments are set up for each test reagent (that is, the number of petri dishes added to each test reagent is 5), and then the test reagents and Petri dishes with cut sections of coleoptiles are placed in a shaker and cultured in the dark for 24 hours or 48 hours. After the culture is completed, the growth amount of each cut section of coleoptiles in each dish is tested, and then the corresponding response of each test reagent is calculated. The average value of the growth amount of all coleoptile segments in the five petri dishes is used as the test result of the growth amount of the coleoptile segments corresponding to the corresponding test reagent. Clear water will be used as the test reagent for the corresponding buds. The test result of the growth amount of the coleoptile section is defined as M, and then the coleoptile growth promotion rate corresponding to each test reagent is calculated. The calculation formula is: coleoptile growth promotion rate (%) = (test result of the growth amount of the coleoptile section - M)/M×100. The number of each test reagent and the active ingredients in each test reagent (2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine, gibberellic acid GA3 and gibberellic acid GA4+7) The concentrations of each test reagent and the corresponding coleoptile growth promotion rates at different culture times are shown in Table 33.
表33各测试试剂的编号、各测试试剂中的有效成分的浓度以及各测试试剂在不同培养时间时对应的胚芽鞘促长率Table 33: The number of each test reagent, the concentration of the active ingredient in each test reagent, and the corresponding coleoptile growth promotion rate of each test reagent at different culture times
由表33可知,实施例1-2的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂均具有促进胚芽鞘生长的作用,并且优于对照药剂(常规植调剂)赤霉酸对胚芽鞘生长的促进作用。It can be seen from Table 33 that the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of Examples 1-2 all have the effect of promoting the growth of coleoptiles, and are better than The control agent (conventional plant conditioning agent) gibberellic acid promotes the growth of coleoptiles.
实验例2Experimental example 2
为了评价实施例3和实施例4的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对农作物生长的影响,以市售0.01%的24-表芸苔素内酯可溶液剂(郑州郑氏化工产品有限公司生产)和市售0.01%的28-高芸苔素内酯可溶液剂(郑州郑氏化工产品有限公司生产)分别作为对照药剂1和对照药剂2,同时以清水作为空白对照,然后将不同制剂采用清水稀释,得到测试试剂。然后测试各测试试剂对花生生长的影响,测试方法如下:选取长势一致的花生田(花生田中的花生均处于幼苗期),随机进行区域划分,每个分区覆盖三垄花生,不同分区之间设置一垄宽度的花生作为保护行,每个分区的面积均为30m2,不同分区做好标识牌,然后用电动喷雾器将不同测试试剂以喷雾的形式均匀喷洒在不同分区的花生植株上,每种测试试剂对应的分区的个数为1个,每个分区内每株花生上喷洒的液体制剂的质量相同,喷雾的方法也相同。最后测试喷药后7d时花生植株的高度、叶绿素含量、蛋白质含量和脂肪含量。其中,花生植株的高度、叶绿素含量、蛋白质含量和脂肪含量的测试方法如下:In order to evaluate the effect of the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Examples 3 and 4 on crop growth, commercially available 0.01% 24 -Epibrassinolide soluble agent (produced by Zhengzhou Zhengshi Chemical Products Co., Ltd.) and commercially available 0.01% 28-homobrassinolide soluble agent (produced by Zhengzhou Zhengshi Chemical Products Co., Ltd.) were used as control agents 1 and control agent 2, while using water as a blank control, and then diluting the different preparations with water to obtain the test reagent. Then test the effect of each test reagent on the growth of peanuts. The test method is as follows: select peanut fields with consistent growth (the peanuts in the peanut fields are all in the seedling stage), randomly divide the areas, each partition covers three ridges of peanuts, and set the settings between different partitions. A row of peanuts with a width of one ridge is used as a protective row. The area of each partition is 30m 2 . Identification boards are made in different partitions, and then different test reagents are evenly sprayed on the peanut plants in different partitions with an electric sprayer in the form of spray. The number of partitions corresponding to the test reagent is 1. The quality of the liquid preparation sprayed on each peanut plant in each partition is the same, and the spraying method is also the same. Finally, the height, chlorophyll content, protein content and fat content of the peanut plants were tested 7 days after spraying. Among them, the testing methods for peanut plant height, chlorophyll content, protein content and fat content are as follows:
(1)株高:每个分区随机选取10个不同位置的花生植株作为取样点,挂牌标记,为保证数据的准确性和代表性,统一测量花生的主茎高度,采用钢制卷尺测量根部至茎尖生长点之间的距离,测量的距离即为该花生植株的主茎高度,以每个分区随机选取的10个花生植株的主茎高度的平均值作为该分区内花生植株的主茎高度的测试结果。(1) Plant height: 10 peanut plants at different locations in each zone were randomly selected as sampling points and marked. In order to ensure the accuracy and representativeness of the data, the height of the main stem of peanuts was measured uniformly, and a steel tape measure was used to measure the height from the root to The distance between the growing points of the stem tips. The measured distance is the main stem height of the peanut plant. The average of the main stem heights of 10 randomly selected peanut plants in each zone is used as the main stem height of the peanut plants in the zone. test results.
(2)叶绿素含量:每个分区随机选取5个不同位置的花生植株作为取样点,挂牌标记。随机测定每个取样点花生植株的上层中除新叶外的所有叶片中的2片叶的叶绿素含量、蛋白质含量和脂肪含量。以每个取样点对应的2片叶的叶绿素含量的平均值作为该取样点花生植株的叶绿素水平代表值,叶绿素含量的测试仪器为KonicaMinoltaSPAD502手持式叶绿素仪;以每个取样点对应的2片叶的蛋白质含量的平均值作为该取样点花生植株的蛋白质水平代表值,蛋白质含量采用全自动凯氏定氮仪进行测定;以每个取样点对应的2片叶的脂肪含量的平均值作为该取样点花生植株的脂肪水平代表值,脂肪含量采用脂肪测定仪进行测定。最后计算每个分区内5个不同位置的花生植株的叶绿素水平代表值的平均值、蛋白质水平代表值的平均值以及脂肪水平代表值的平均值,以计算的平均值分别作为该分区内花生植株的叶绿素含量的测试结果、蛋白质含量的测试结果和脂肪含量的测试结果。(2) Chlorophyll content: 5 peanut plants at different locations in each zone were randomly selected as sampling points and marked. The chlorophyll content, protein content and fat content of 2 leaves in all leaves except new leaves in the upper layer of peanut plants at each sampling point were randomly measured. The average value of the chlorophyll content of the two leaves corresponding to each sampling point was used as the representative value of the chlorophyll level of the peanut plant at that sampling point. The testing instrument for the chlorophyll content was the Konica Minolta SPAD502 handheld chlorophyll meter; the average value of the two leaves corresponding to each sampling point was The average value of the protein content of the peanut plants at the sampling point was used as the representative value of the protein level of the peanut plant at the sampling point. The protein content was measured using a fully automatic Kjeldahl nitrogen analyzer; the average value of the fat content of the two leaves corresponding to each sampling point was used as the sampling point. Representative values of fat levels in peanut plants, and fat content was measured using a fat meter. Finally, calculate the average of the representative values of chlorophyll level, the average of protein level and the average of the representative value of fat level of the peanut plants at 5 different positions in each partition, and use the calculated average values as the average values of the peanut plants in the partition. The test results of chlorophyll content, protein content and fat content.
各测试试剂的编号、各测试试剂中的有效成分(2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺、24-表芸苔素内酯和28-高芸苔素内酯)的浓度以及使用各测试试剂后花生的株高、叶绿素含量、蛋白质含量和脂肪含量的测试结果如表34所示。The number of each test reagent, the active ingredients in each test reagent (2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine, 24-epibrassinolide and 28-high brassinolide Lactone) concentration and the test results of peanut plant height, chlorophyll content, protein content and fat content after using each test reagent are shown in Table 34.
表34各测试试剂的编号、各测试试剂中的有效成分的浓度以及使用各测试试剂后花生的株高、叶绿素含量、蛋白质含量和脂肪含量的测试结果Table 34: The number of each test reagent, the concentration of active ingredients in each test reagent, and the test results of peanut plant height, chlorophyll content, protein content and fat content after using each test reagent
由表34可知,实施例3-4的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂均具有促进花生植株长高的作用,并且与空白对照组(清水)相比,实施例3-4的液体制剂均可明显提高花生植株的叶片中的叶绿素含量、蛋白质含量和脂肪含量,可显著促进花生的生长,提高叶绿素积累量,从而有利于光合产物的积累,促进饱果、增产提质。It can be seen from Table 34 that the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Examples 3-4 all have the effect of promoting the growth of peanut plants, and are consistent with Compared with the blank control group (clear water), the liquid preparations of Examples 3-4 can significantly increase the chlorophyll content, protein content and fat content in the leaves of peanut plants, can significantly promote the growth of peanuts, increase the amount of chlorophyll accumulation, and thus have It is conducive to the accumulation of photosynthetic products, promotes full fruit, increases yield and improves quality.
实验例3Experimental example 3
为了评价实施例5和实施例6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对农作物生长的影响,以市售30%的胺鲜酯·乙烯利水剂(郑州郑氏化工产品有限公司生产)为对照药剂,同时以清水为空白对照,然后将不同制剂采用清水稀释,得到测试试剂。再按照标准GB/T17980.145-2004《农药田间药效试验准则(二)》中的方法以长势相同的富士苹果为实验对象进行实施。于坐果期、膨果期分别将测试试剂均匀喷施于苹果植株的茎叶上,每种测试试剂喷施的苹果植株的面积均为1亩,且每株苹果植株上每次喷施的测试试剂的质量相同,每次喷过测试试剂后,第3d时调查有无药害,同时调查坐果率、单果重量、品质等数据,并且测试鲜果中维生素C的含量以及苹果果实的硬度,测试时从每种测试试剂喷施的所有苹果植株中随机选取5株作为测试样品,以5株测试结果的平均值作为使用相应测试试剂后苹果的坐果率、单果重量、鲜果中维生素C的含量以及苹果果实的硬度的测试结果。In order to evaluate the effect of the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Examples 5 and 6 on crop growth, 30% of the commercially available amine Fresh ester·ethephon aqueous agent (produced by Zhengzhou Zhengshi Chemical Products Co., Ltd.) was used as the control agent, and water was used as the blank control. Then different preparations were diluted with water to obtain test reagents. Then according to the method in the standard GB/T17980.145-2004 "Pesticide Field Efficacy Test Guidelines (2)", Fuji apples with the same growth rate were used as the experimental subjects. Spray the test reagents evenly on the stems and leaves of the apple plants during the fruit setting and fruit expansion stages. The area of the apple plants sprayed with each test reagent is 1 mu, and the test results of each spray on each apple plant are The quality of the reagents is the same. After each test reagent is sprayed, the presence of phytotoxicity will be investigated on the 3rd day. At the same time, the fruit setting rate, single fruit weight, quality and other data will be investigated, and the vitamin C content in the fresh fruit and the hardness of the apple fruit will be tested. During the test Randomly select 5 apple plants from all the apple plants sprayed with each test reagent as test samples, and use the average of the test results of the 5 plants as the fruit setting rate, single fruit weight, vitamin C content in fresh fruits and apples after using the corresponding test reagent. Fruit firmness test results.
各测试试剂的编号、各测试试剂中的有效成分(2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺、胺鲜酯和乙烯利)的浓度以及使用各测试试剂后苹果的坐果率、单果重量、鲜果中维生素C的含量以及苹果果实的硬度的测试结果如表35所示。The number of each test reagent, the concentration of the active ingredients in each test reagent (2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine, ampicillin and ethephon) and the use of each test reagent The test results of apple fruit setting rate, single fruit weight, vitamin C content in fresh fruit and apple fruit hardness after testing the reagent are shown in Table 35.
表35各测试试剂的编号、各测试试剂中的有效成分的浓度以及各测试试剂在不同培养时间时对应的胚芽鞘促长率Table 35: The number of each test reagent, the concentration of the active ingredient in each test reagent, and the corresponding coleoptile growth promotion rate of each test reagent at different culture times
由表35可知,采用实施例5-6的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对苹果树喷施后,苹果的坐果率有所提高,单果的重量也有所增加,并且果实中的维生素C的含量也有所提高。It can be seen from Table 35 that after the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of Example 5-6 is sprayed on apple trees, the fruit setting rate of apples The weight of the single fruit has also increased, and the vitamin C content in the fruit has also increased.
实验例4Experimental example 4
为了评价实施例7和实施例8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对农作物生长的影响,以市售0.1%三十烷醇可溶液剂(浙江大鹏药业股份有限公司生产)为对照药剂,同时以清水为空白对照,然后将不同制剂采用清水稀释,得到测试试剂。然后以品种为台农一号的芒果为测试对象,测试时,同一种测试试剂施用的芒果树共有5棵,且每棵树只施用一种测试试剂,用药前,每棵树按东、南、西、北、中五个方向,每个方向标记3个花絮(花絮上的幼果的直径均为0.8~1cm,花絮上的幼果的总量保持一致),然后将标记的花絮浸入测试试剂中,以使测试试剂对幼果进行浸泡,试验周期内共用药2次,两次用药间隔7天,每次用药时每个花絮浸泡测试试剂的时间相同,第一次用药前的当天调查果实的纵横径,然后第一次用药后的第7天调查果实纵横径的同时进行第二次用药,第二次用药后的第7天调查果实纵横径,最后计算第一次用药后的第7天时的果实纵横径相比于第一次用药前的当天的果实纵横径的增长量以及第二次用药后的第7天时的果实纵横径相比于第一次用药前的当天的果实纵横径的增长量。最后计算每一种测试试剂施用的5棵芒果树上所有标记的果实在第一次用药后的第7天时的果实纵横径的增长量的平均值以及第二次用药后的第7天时的果实纵横径的增长量的平均值。In order to evaluate the effect of the liquid preparations containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine in Examples 7 and 8 on crop growth, commercially available 0.1% 30 Alkanol soluble agent (produced by Zhejiang Dapeng Pharmaceutical Co., Ltd.) was used as the control agent, and water was used as the blank control. Then different preparations were diluted with water to obtain test reagents. Then the mango variety Tainong No. 1 was used as the test object. During the test, a total of 5 mango trees were applied with the same test reagent, and only one test reagent was applied to each tree. Before application, each tree was divided into east and south. , west, north, and center, mark 3 tidbits in each direction (the diameter of the young fruits on the tidbits are all 0.8-1cm, and the total amount of young fruits on the tidbits remains the same), and then immerse the marked tidbits for testing In the reagent, the test reagent is used to soak the young fruits. The drug is used twice during the test period. The interval between the two treatments is 7 days. Each tidbit is soaked in the test reagent for the same time during each use. Survey on the day before the first use of the drug. The longitudinal and transverse diameters of the fruits were measured, and then the longitudinal and transverse diameters of the fruits were measured on the 7th day after the first application of the medication. The second application of the medication was performed at the same time. The longitudinal and transverse diameters of the fruits were measured on the 7th day after the second application of the medication. Finally, the vertical and horizontal diameters of the fruits were measured on the 7th day after the first medication. The growth of the longitudinal and transverse diameter of the fruit on the 7th day compared to the vertical and horizontal diameter of the fruit on the day before the first application of the medication, and the vertical and horizontal diameter of the fruit on the 7th day after the second application of the medication compared with the vertical and horizontal diameter of the fruit on the day before the first application of the medication. diameter growth. Finally, calculate the average growth of the longitudinal and transverse diameters of all marked fruits on the 5 mango trees treated with each test agent on the 7th day after the first application and the average growth of the fruit on the 7th day after the second application. The average increase in longitudinal and transverse diameters.
各测试试剂的编号、各测试试剂中的有效成分(2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺和三十烷醇)的浓度以及使用各测试试剂后第一次用药后的第7天时的果实纵横径的增长量以及第二次用药后的第7天时的果实纵横径的增长量如表36所示。The number of each test reagent, the concentration of the active ingredients (2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine and triacontanol) in each test reagent, and the use of each test reagent The growth amount of the longitudinal and transverse diameter of the fruit on the 7th day after the first administration of the drug and the growth amount of the longitudinal and transverse diameter of the fruit on the 7th day after the second administration are shown in Table 36.
表36各测试试剂的编号、各测试试剂中的有效成分的浓度以及各测试试剂对芒果幼果的果实纵横径的增长量Table 36: The number of each test reagent, the concentration of the active ingredient in each test reagent, and the increase in the vertical and horizontal diameter of the young mango fruit by each test reagent
由表36可知,相比于清水而言,采用实施例7-8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对芒果幼果浸泡后,能够促进果实的纵径和横径的增长,并且随着有效成分的浓度的增大,促进效果明显提升。另外,当有效成分浓度相同时,与对照药剂相比,第二次施用实施例7-8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂后的第7天时,芒果果实的纵径和横径的增长量明显更大,说明实施例7-8的含有2-氟-N-(3-甲氧基苯基)-7H-嘌呤-6-胺的液体制剂对芒果幼果的生长具有更好的促进作用。As can be seen from Table 36, compared with clear water, the use of the liquid preparation containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine of Example 7-8 has better effects on young mango fruits. After soaking, it can promote the growth of the longitudinal and transverse diameters of the fruit, and as the concentration of active ingredients increases, the promotion effect is significantly improved. In addition, when the active ingredient concentration is the same, compared with the control agent, the second administration of Example 7-8 containing 2-fluoro-N-(3-methoxyphenyl)-7H-purin-6-amine On the 7th day after the liquid preparation, the growth of the longitudinal diameter and transverse diameter of the mango fruit was significantly greater, indicating that Examples 7-8 contained 2-fluoro-N-(3-methoxyphenyl)-7H-purine. The liquid preparation of -6-amine has a better promoting effect on the growth of young mango fruits.
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