WO1997025054A1 - An antibacterial or antiviral pharmaceutical composition and preparation thereof - Google Patents

An antibacterial or antiviral pharmaceutical composition and preparation thereof Download PDF

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Publication number
WO1997025054A1
WO1997025054A1 PCT/CN1997/000001 CN9700001W WO9725054A1 WO 1997025054 A1 WO1997025054 A1 WO 1997025054A1 CN 9700001 W CN9700001 W CN 9700001W WO 9725054 A1 WO9725054 A1 WO 9725054A1
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Prior art keywords
total
forsythia
baicalin
honeysuckle
preparation
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PCT/CN1997/000001
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French (fr)
Chinese (zh)
Inventor
Hong Li
Leting Wu
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Hong Li
Leting Wu
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Application filed by Hong Li, Leting Wu filed Critical Hong Li
Priority to AU13644/97A priority Critical patent/AU1364497A/en
Publication of WO1997025054A1 publication Critical patent/WO1997025054A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/35Caprifoliaceae (Honeysuckle family)
    • A61K36/355Lonicera (honeysuckle)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539Scutellaria (skullcap)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/63Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A61K36/634Forsythia

Definitions

  • the present invention relates to a pharmaceutical composition and a preparation method thereof. More specifically, the present invention relates to an antibacterial and antiviral pharmaceutical composition and a preparation method thereof.
  • Shuanghuanglian powder has the Chinese patent and the invention patent number is 891036-8.
  • the preparation of Shuanghuanglian powder has the Chinese patent and the invention patent number is 891036-8.
  • impurities low purity, dark colors, and injections. Pain, allergic reactions; and honeysuckle, even 3 ⁇ 4 Hemolytic saponins and tannins are difficult to remove by this process.
  • the purpose of the present invention is to overcome the shortcomings, provide an antibacterial antiviral pharmaceutical composition with good curative effect, small dose, high purity, and low irritation and provide a preparation method thereof.
  • the antibacterial and antiviral pharmaceutical composition provided by the present invention contains 0.02-98.18% of baicalin total glycosides extracted from Scutellaria baicalensis, 0.02-98.18% of forsythia glucosides extracted from forsythia or forsythia leaves and optionally contains excipients Agent.
  • the pharmaceutical composition further contains 0.40-88.10% of the total organic acid of honeysuckle extracted from honeysuckle or honeysuckle leaves.
  • excipients used in the pharmaceutical composition of the present invention are pharmaceutically conventional excipients, such as Span 85, ethyl oleate, dichloromethane, mixed fatty acid glycerol vinegar (type 34), cyclodextrin, sugar Powder, menthol, water tablets, magnesium stearate, acrylic resin, stevioside, etc.
  • the pharmaceutical composition of the present invention can be made into various dosage forms, such as aerosol, according to the specific conditions and conventional preparation techniques Preparations, suppositories, lozenges, capsules; tinctures, water injections, powder injections and so on.
  • baicalin also contains baicalein, baicalin and other flavonoids. Due to the highest baicalin content and clear pharmacological action, baicalin is used as an index to extract total baicalin, and conventional analysis methods such as ultraviolet spectrophotometry are used. "'1 content, baicalin content in total baicalin
  • baicalin in total baicalin is> 86% when preparing injections
  • Forsythia in addition to forsythia vinegar contains saponin, tannin, volatile oil, forsythia, and other ingredients.
  • the hemolytic saponins and tannins need to be removed.
  • the forsythia glycosides were extracted by using forsythia vinegar ring as an index, and the content was determined by conventional analytical methods such as ultraviolet spectrophotometry.
  • the content of forsythiaside in forsythia glycosides should be> 10%; Free of tannins and hemolytic saponins, containing forsythiaside> 25%
  • Honeysuckle contains organic acids such as dicaffeoquinic acid and caffeic acid, as well as lutein, saponin, tannin, etc. in addition to chlorogenic acid. According to the extraction method described in the present invention, the above components can be prepared; It is necessary to remove tannins and hemolytic soaps. Because chlorogenic acid has the highest content and is the main active ingredient of antibacterial, the total organic acids of honeysuckle are extracted with chlorogenic acid as an indicator, and routine analysis such as ultraviolet spectrophotometry is used; 3 ⁇ 4 ⁇ method Content, the content of chlorogenic acid in total organic acids of honeysuckle should be> 10%; the total organic acid of honeysuckle does not contain tannins and hemolytic saponins when preparing injections, and contains chlorogenic acid> 25%.
  • the above active ingredients (such as total scutellaria baicalensis, total forsythia glucosides, total honeysuckle organic acids) and excipients are combined to obtain the pharmaceutical composition of the present invention.
  • the method for preparing the pharmaceutical composition of the present invention can make the pharmaceutical composition of the present invention have good curative effect, small dosage, and remove saponin (caused by hemolysis) and tannin (caused by pain) existing in the fins and honeysuckle. Advantages of high purity and low irritation.
  • the preparation method of the present invention includes the following steps:
  • baicalin total baicalsides or baicalin are prepared for oral use; or the obtained total baicalin or baicalin is suspended in water for injection under sterile conditions, and the pH is adjusted to 7.0- 8.0, filter, concentrate, and dry; or pour the concentrate into ethanol to precipitate and dry the precipitate to obtain the total baicalin or baicalin for injection;
  • a refined forsythia glycoside that removes tannins and hemolytic saponins can be obtained; or, Forsythia suspensa or Forsythia suspensa leaves are extracted according to conventional methods.
  • the extraction solution is adsorbed with an adsorbent such as polyamide, macroporous adsorption resin, and silica gel.
  • an adsorbent such as polyamide, macroporous adsorption resin, and silica gel.
  • the solvent is eluted with water, ethanol, acetone, and ethyl acetate to obtain Remove tannin and hemolytic soap forsythia total glycosides or forsythia glycosides; if necessary, (ii) mix the above active ingredients with excipients.
  • step (i) further includes:
  • n-butanol extract uses sodium bicarbonate-sodium hydrogen phosphate or pH 7 .0 ⁇ 8.0 buffer extraction, adjust the pH of the extract to 5.0 ⁇ 7.0, add 1-15% gelatin solution, egg white solution or other precipitant dropwise to complete the tannin precipitation. After conventional treatment, the tannin can be removed. And total organic acids of gold and silver of hemolytic saponins;
  • honeysuckle or leaves and extract them according to conventional methods.
  • the extraction solution is adsorbed with an adsorbent such as polymillamine, macroporous adsorption resin, silica gel, etc.
  • an adsorbent such as polymillamine, macroporous adsorption resin, silica gel, etc.
  • the solvent is eluted with water, alkaline water, ethanol, or acrylic acid to obtain Remove the total organic acids of honeysuckle from tannins and blood saponins.
  • baicalin 58 g The above total baicalin was recrystallized from ethanol to obtain baicalin 58 g .
  • honeysuckle medicinal material or honeysuckle leaf Take 1000g of honeysuckle medicinal material or honeysuckle leaf, extract 12 to 4 times with 12 times the amount of 60% ethanol, recover the solvent under reduced pressure, add water to make a 100% aqueous solution containing the medicinal material, and then extract with the same amount of n-butanol to recover from the extract Solvent, dried to obtain 76g of total honeysuckle organic acids.
  • the solvent was recovered from the n-butanol extract to 100% of the medicinal material, and extracted three times with an equivalent amount of 5% sodium bicarbonate aqueous solution.
  • the alkaline aqueous solution was adjusted to pH 0-7.0, and the 3% gelatin solution was added dropwise to completely precipitate the tannin. , Standing, filtering, concentrating, and drying, so as to remove the total organic acids 5 of tannins and hemolytic saponins; or
  • honeysuckle medicinal material or honeysuckle leaf extract 12 to 4 times with 12 times the amount of 60% ethanol, recover the solvent under reduced pressure, adsorb with macroporous adsorption resin, wash away impurities with distilled water, and elute with ethanol to remove tan.
  • Honeysuckle and Organic Hemolytic Saponin 85g.
  • Method Crush the total glucosides of Scutellaria baicalensis, total organic acids of honeysuckle and total glycosides of forsythia, pass through 80-120 mesh sieve, mix well, add to the suppository base that has been heated and melted, stir well, inject into the suppository mold and cool , Cutting, packaging, serving as suppositories.
  • Example 6 Tablets and preparation method
  • Preparation method Wrap total glucoside glycosides and cyclodextrin, mix with total cilantro ring, honeysuckle total organic acid, powdered sugar, make granules, spray into menthol and borneol ethanol solution, add magnesium stearate, mix Evenly, press the tablet to obtain a tablet.
  • Forsythia total glycosides and honeysuckle total organic acids are made into granules by dry method, coated with acrylic resin film, and differently colored, mixed with baicalone total glycoside granules, and obtained in empty capsules.
  • Preparation method Dissolve total organic acids of honeysuckle and total forsythia glycosides with water for injection, adjust pH 5.0-7.0, filter, and add 3% gelatin solution dropwise to complete tannin precipitation, let stand, filter, and add saturated filtrate
  • the bile alcohol solution completely precipitated the saponin, filtered, and the filtrate was added to the total scutellaria baicalensis to suspend.
  • the sodium bicarbonate-sodium carbonate solution was used to adjust the pH to 6.-.5 to dissolve. After heating, refrigerating, filtering, ultrafiltration, etc., Encapsulation, sterilization, that is, 4 injections; or concentrated, dry, sterile packaging, to obtain powder injection.
  • Example 10 Water injection, powder injection and preparation method
  • Preparation method According to the prescription amount, refined forsythia total glycosides for removing tannin and hemolytic saponin, refined organic acids for removing tannin and hemolytic soap type honeysuckle are dissolved with water for injection, and added to the scutellaria baicalensis for suspension Add sodium bicarbonate-sodium arsenate dropwise to adjust the pH to 7.0-7.5 to dissolve. After heating, refrigerating, filtering or ultrafiltration, seal and sterilize to obtain the injection solution; or concentrate, dry, and sterilize Installed to get powder injection.
  • Example 12 Water injection, powder injection and preparation method
  • Method Suspend baicalin in distilled water according to the prescribed amount, adjust the pH to 7.0-8.0 with 40% sodium hydroxide solution, concentrate, dry, or add ethanol to precipitate the baicalin sodium salt, and filter the precipitate. Dry and pulverize to obtain the baicalin salt material for injection. Dissolve chlorogenic acid, dicaffeine quinic acid and dihydrogenin in water for injection, filter, and drop the filtrate to adjust the pH 6.5- 7.5, filter, concentrate, dry, pulverize, distribute into ampoules under sterile conditions, then load the baicalin salt, and seal to obtain the powder injection.
  • Preparation method Dissolve 3 ⁇ 4 total glycosides from which tannins and hemolytic saponins are removed, and add The total glucosides of baicale for injection were adjusted to pH 6.5-7.5 with a sodium bicarbonate solution. After conventional processing such as heating, refrigerating, potting and sterilization, water injection was obtained.
  • Preparation method Dissolve refined forsythia total glycosides for removing tannin and hemolytic saponin with water for injection, add sodium bicarbonate solution dropwise to adjust pH 6.5-7.5, after conventional treatment, dry, crush, and Under bacterial conditions, aliquoted into a sterilized container, and then filled with Scutellaria baicalensis for injection, sealed, to obtain a powder injection.
  • the pharmacodynamic test of the pharmaceutical composition of the present invention proves that the antibacterial effect is better than that of Shuanghuanglian preparation, and the anti-embedging virus effect is similar to that of Shuanghuanglian preparation.
  • the test results are as follows:
  • the in-tube antibacterial test proves that the composition of the present invention has a strong antibacterial effect, and has an antibacterial effect on Streptococcus group A, pneumococcus, influenzae bacillus, dysentery bacillus, and Pseudomonas aeruginosa, which are 1 to 2 higher than the Shuanghuanglian preparation. Dilution.
  • the experimental results are shown in Tables 1 and 2.
  • the pharmaceutical composition containing total scutellaria baicalensis and total forsythia glycosides and no total organic honeysuckle ⁇ has a slight weakened antibacterial effect, among which antibacterial action against diphtheria and bacillus -t. Contains gold and silver The pharmaceutical composition of total organic acids in flowers is similar, and the antibacterial effect on other strains is one dilution lower; the anti-syncytial virus effect is similar.

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Abstract

An antibacterial or antiviral pharmaceutical composition and preparation thereof are disclosed. The composition comprises the active components which are respectively extracted from the roots of Scutellaria baicalensis, the fructus and the leaves of Forsythia suspensa, if necessary, and the flower buds and the leaves of Lonicera joponica, and a conventional pharmaceutical excipient. During the preparing process the attention is paid to the tannin and blood-dissolving saponin are removed and the active component unstable to acids and alkalis is protected. Therefore, the composition has advantages including high purity, small dosage, good potency and little irritation. It can be formulated in the various dosage forms by simple method and be suitable for industrial production.

Description

抗菌抗病毒药物组合物及其制备方法  Antibacterial and antiviral medicine composition and preparation method thereof
发明领域 Field of invention
本发明涉及药物组合物及其制备方法. 更具体地说, 本发明涉及抗 菌抗病毒药物组合物及其制备方法.  The present invention relates to a pharmaceutical composition and a preparation method thereof. More specifically, the present invention relates to an antibacterial and antiviral pharmaceutical composition and a preparation method thereof.
发明背景 Background of the invention
现有的中成药制剂多以传统的方法制备, 成品杂质多, 剂量大, 生 物利用度低, 而且不清楚有效成分是什么, 更无法控制其有效成分含量 及内在质量, 致使我国许多历史悠久, 疗效确切, 使用广泛, 国内知名 度很高的中成药制剂得不到国际社会的认可, 使用范围仅限于中国、 曰 本及东南亚部分地区; 如三九胃秦冲剂, 虽然通过了美国 FDA的批准, 进入了美国市场, 但仅是以保健食品的形式获得批准的, 国际上不承认 这些中成药是药品. 又如, 由黄芩、 金银花、 连翘组成, 用于治疗上呼 吸道感染、 具有抗菌抗病毒作用的双黄连制剂, 其中, 双黄连粉针剂制 备工艺已获中国专利,发明专利号为 891036 ― 8,但由于该以中药原材 料进行粗加工制成注射剂, 杂质多, 纯度低, 颜色深, 注射疼痛, 有过 敏反应; 而且金银花、 连¾中含有溶血性皂甙和鞣质, 该工艺难以将其 除去; 同时, 由于处方中主要有效成分在酸碱条件下极不稳定, 而该工 艺采用酸减处理时并未注意给予保护, 致使有效成分大部分被破坏. 本发明的目的在于克服上迷缺点, 提供一种疗效好、 剂量小、 纯度 高、 剌激性小的抗菌抗病毒药物组合物并提供其制备方法.  Most of the existing proprietary Chinese medicine preparations are prepared by traditional methods. The finished product has many impurities, large dosages, low bioavailability, and it is not clear what the active ingredients are, and it is impossible to control the active ingredient content and intrinsic quality, which has caused a lot of history in China. The curative effect is accurate, widely used, and the well-known Chinese patent medicine preparations in China are not recognized by the international community. The scope of use is limited to China, Japan and parts of Southeast Asia; such as Sanjiuweiqin granules, although approved by the US FDA, Entered the US market, but was only approved in the form of health food. These proprietary Chinese medicines are not recognized internationally as medicines. For example, it consists of scutellaria baicalensis, honeysuckle and forsythia. It is used to treat upper respiratory infections and has antibacterial and antiviral properties. The preparation of Shuanghuanglian powder has the Chinese patent and the invention patent number is 891036-8. However, due to the rough processing of traditional Chinese medicine raw materials to make injections, there are many impurities, low purity, dark colors, and injections. Pain, allergic reactions; and honeysuckle, even ¾ Hemolytic saponins and tannins are difficult to remove by this process. At the same time, the main active ingredients in the prescription are extremely unstable under acid and alkali conditions, and the process does not pay attention to protection when acid subtraction treatment is used, resulting in most of the active ingredients Destroyed. The purpose of the present invention is to overcome the shortcomings, provide an antibacterial antiviral pharmaceutical composition with good curative effect, small dose, high purity, and low irritation and provide a preparation method thereof.
发明详述 Detailed description of the invention
本发明提供的抗菌抗病毒药物组合物含有 0.02 - 98.18%从黄芩中 提取的黄芩总甙, 0.02-98.18%从连翘或连翘叶中提取的连翘总甙以及 逸择性地含有賦形剂. 本发明的另一实施方案中, 药物组合物还含有 0.40-88.10%从金银花或金银花叶中提取的金银花总有机酸.  The antibacterial and antiviral pharmaceutical composition provided by the present invention contains 0.02-98.18% of baicalin total glycosides extracted from Scutellaria baicalensis, 0.02-98.18% of forsythia glucosides extracted from forsythia or forsythia leaves and optionally contains excipients Agent. In another embodiment of the present invention, the pharmaceutical composition further contains 0.40-88.10% of the total organic acid of honeysuckle extracted from honeysuckle or honeysuckle leaves.
本发明的药物组合物中所用赋形剂是药学上常规的赋形剂, 例如司 盘 85、 油酸乙醏、 二氯二氡甲烷, 混合脂肪酸甘油醋( 34型) 、 环糊 精、 糖粉、 薄荷脑、 水片、 硬脂酸镁、 丙烯酸树脂、 甜菊甙等等. 本发 明药物组合物可根据具体情况按常规制备技术制成各种剂型, 例如气雾 剂、 栓剂、 含片、 胶囊剂; 潁粒剂、 水针剂、 粉针剂等等。 The excipients used in the pharmaceutical composition of the present invention are pharmaceutically conventional excipients, such as Span 85, ethyl oleate, dichloromethane, mixed fatty acid glycerol vinegar (type 34), cyclodextrin, sugar Powder, menthol, water tablets, magnesium stearate, acrylic resin, stevioside, etc. The pharmaceutical composition of the present invention can be made into various dosage forms, such as aerosol, according to the specific conditions and conventional preparation techniques Preparations, suppositories, lozenges, capsules; tinctures, water injections, powder injections and so on.
黄芩中除含有黄芩甙外尚含有黄芩素、 汉黄芩甙等黄 类成分, 由 于黄芩甙含量最高且药理作用明确, 故以黄芩甙为指标提取黄芩总甙, 并用紫外分光光度法等常规分析方法《'1定含量, 黄芩总甙中黄芩甙含量 In addition to baicalin, baicalin also contains baicalein, baicalin and other flavonoids. Due to the highest baicalin content and clear pharmacological action, baicalin is used as an index to extract total baicalin, and conventional analysis methods such as ultraviolet spectrophotometry are used. "'1 content, baicalin content in total baicalin
>70 %; 制备注射剂时, 黄芩总甙中黄芩甙含量>86%; > 70%; The content of baicalin in total baicalin is> 86% when preparing injections;
连翹中除含有连翘醋武外尚含有皂甙、 鞣质、 挥发油、 连翘朌等成 分, 制备注射剂时需将溶血性皂甙、 鞣质除去. 由于连翘 g§甙含量最高 且药理作用明确, 故以连翘醋戒为指标提取连翘总甙, 并用紫外分光光 度法等常规分析方法测定含量, 连翘总甙中连翘醋甙含量应 >10%; 制 备注射剂时连翘总甙中不含鞣质及溶血性皂甙, 含连翘酯甙 >25%.  Forsythia in addition to forsythia vinegar contains saponin, tannin, volatile oil, forsythia, and other ingredients. For the preparation of injections, the hemolytic saponins and tannins need to be removed. Because forsythia has the highest g glycoside content and clear pharmacological effects Therefore, the forsythia glycosides were extracted by using forsythia vinegar ring as an index, and the content was determined by conventional analytical methods such as ultraviolet spectrophotometry. The content of forsythiaside in forsythia glycosides should be> 10%; Free of tannins and hemolytic saponins, containing forsythiaside> 25%
金银花中除含有绿原酸外尚含有二咖啡酰奎宁酸、 咖啡 酸等有机 酸及黄^、 皂甙、 鞣质等成分, 按照本发明所述的提取方法, 上述成分 均可提出; 制备注射剂时需将鞣质及溶血性皂式除去; 由于绿原酸含量 最高且为抗菌主要有效成分, 故以绿原酸为指标提取金银花总有机酸, 并用紫外分光光度法等常规分析; ¾Γ法測定含量, 金银花总有机酸中绿原 酸含量应>10%; 制备注射剂时金银花总有机酸中不含鞣质及溶血性皂 甙, 含绿原酸>25%.  Honeysuckle contains organic acids such as dicaffeoquinic acid and caffeic acid, as well as lutein, saponin, tannin, etc. in addition to chlorogenic acid. According to the extraction method described in the present invention, the above components can be prepared; It is necessary to remove tannins and hemolytic soaps. Because chlorogenic acid has the highest content and is the main active ingredient of antibacterial, the total organic acids of honeysuckle are extracted with chlorogenic acid as an indicator, and routine analysis such as ultraviolet spectrophotometry is used; ¾Γ method Content, the content of chlorogenic acid in total organic acids of honeysuckle should be> 10%; the total organic acid of honeysuckle does not contain tannins and hemolytic saponins when preparing injections, and contains chlorogenic acid> 25%.
上述活性成分(例如黄芩总武、 连翘总甙、 金银花总有机酸)与赋 形剂组合即得本发明的药物组合物.  The above active ingredients (such as total scutellaria baicalensis, total forsythia glucosides, total honeysuckle organic acids) and excipients are combined to obtain the pharmaceutical composition of the present invention.
本发明的制备药物组合物的方法通过除去连翅、 金银花中存在的皂 甙(造成溶血的原因)和鞣质(造成疼痛的原因), 可使本发明的药物 组合物具有疗效好、 剂量小、 纯度高、 刺激性小的优点. 具体地说, 本 发明的制备方法包括下列步稞:  The method for preparing the pharmaceutical composition of the present invention can make the pharmaceutical composition of the present invention have good curative effect, small dosage, and remove saponin (caused by hemolysis) and tannin (caused by pain) existing in the fins and honeysuckle. Advantages of high purity and low irritation. Specifically, the preparation method of the present invention includes the following steps:
( i )制备活性成分:  (i) Preparation of active ingredients:
( a )制备黄芩总甙: 按常规方法从黄芩制备口服用的黄芩总甙或 黃芩甙; 或再将所得黄芩总甙或黄芩甙在无菌条件下用注射用水混悬, 调 pH7.0-8.0, 过滤、 浓缩、 干燥; 或将浓缩液倾入乙醇中使沉淀, 将 沉淀干燥, 即得注射用黄芩总甙或黄芩甙;  (a) Preparation of baicalin total glucosides: According to conventional methods, baicalin total baicalsides or baicalin are prepared for oral use; or the obtained total baicalin or baicalin is suspended in water for injection under sterile conditions, and the pH is adjusted to 7.0- 8.0, filter, concentrate, and dry; or pour the concentrate into ethanol to precipitate and dry the precipitate to obtain the total baicalin or baicalin for injection;
( b ) 制备连翘总武:  (b) Preparation of forsythia total martial arts:
取连翘或连翘叶, 按常规方法提取, 浓缩后用正丁醇等有机溶剂萃 取, 经常规处理得口服剂-、 气雾剂、 栓剂等用连翹总甙; 将上述连翘总 甙用水溶解, 滴加 1 - 15 %明胶液、蛋清液或其它沉淀剂使鞣质沉淀完 全、 静置, 过滤, 滤液滴加饱和的胆笛醇乙醇液或其它沉淀剂使皂甙沉 淀完全, 经常规处理, 即得精制的除去鞣质及溶血性皂甙的连翘总甙; 或者, 取连翘或连翘叶, 按常规方法提取, 提取液用聚酰胺、 大孔 吸附树脂、 硅胶等吸附剂吸附, 洗去杂质后, 用水、 乙醇、 丙酮、 乙酸 乙酯等溶剂洗脱, 即得除去鞣质及溶血性皂武的连翘总甙或连翘醏甙; 需要的话, ( ii )将上述活性成分与赋形剂混合. Take forsythia or forsythia leaves, extract them by conventional methods, and concentrate with organic solvents such as n-butanol Take the forsythia total glycosides for oral preparations, aerosols, suppositories, etc. after conventional treatment; dissolve the forsythia total glycosides in water, and add 1-15% gelatin solution, egg white solution or other precipitants dropwise to precipitate tannins Completely, let it stand, filter, and add the saturated solution of bile alcohol ethanol or other precipitating agent to the precipitate to completely precipitate the saponin. After conventional treatment, a refined forsythia glycoside that removes tannins and hemolytic saponins can be obtained; or, Forsythia suspensa or Forsythia suspensa leaves are extracted according to conventional methods. The extraction solution is adsorbed with an adsorbent such as polyamide, macroporous adsorption resin, and silica gel. After impurities are washed away, the solvent is eluted with water, ethanol, acetone, and ethyl acetate to obtain Remove tannin and hemolytic soap forsythia total glycosides or forsythia glycosides; if necessary, (ii) mix the above active ingredients with excipients.
在本发明制备方法的另一实施方案中, 上述步稞( i ) 中还包括: In another embodiment of the preparation method of the present invention, the step (i) further includes:
( c )制备金银花总有机酸: (c) Preparation of total organic acids of honeysuckle:
取金银花或叶, 按常规方法提取, 浓缩后用正丁醇等有机溶剂萃 取, 即得口服制剂、 气雾剂、 栓剂用原料; 上述正丁醇萃取液用碳酸氢 钠-磷酸氢钠或 pH7.0〜8.0 的緩冲液萃取, 萃取液调 pH5.0〜7.0, 滴加 1 - 15 %的明胶液、蛋清液或其它沉淀剂使鞣质沉淀完全,经常规处理, 即得除去鞣质及溶血性皂甙的金银 总有机酸;  Take honeysuckle or leaves, extract them according to conventional methods, and concentrate them with organic solvents such as n-butanol to obtain raw materials for oral preparations, aerosols, suppositories; the above-mentioned n-butanol extract uses sodium bicarbonate-sodium hydrogen phosphate or pH 7 .0 ~ 8.0 buffer extraction, adjust the pH of the extract to 5.0 ~ 7.0, add 1-15% gelatin solution, egg white solution or other precipitant dropwise to complete the tannin precipitation. After conventional treatment, the tannin can be removed. And total organic acids of gold and silver of hemolytic saponins;
或者, 取金银花或叶, 按常规方法提取, 提取液用聚銑胺、 大孔吸 附树脂、 硅胶等吸附剂吸附, 洗去杂质后, 用水、 碱水、 乙醇、 丙 等 溶剂洗脱, 即得除去鞣质及^血性皂甙的金银花总有机酸.  Alternatively, take honeysuckle or leaves and extract them according to conventional methods. The extraction solution is adsorbed with an adsorbent such as polymillamine, macroporous adsorption resin, silica gel, etc. After the impurities are washed away, the solvent is eluted with water, alkaline water, ethanol, or acrylic acid to obtain Remove the total organic acids of honeysuckle from tannins and blood saponins.
现通过下面的非限定性实施例进一步阐述本发明 .  The invention is further illustrated by the following non-limiting examples.
实施例  Examples
实施例 1 制备黄芩总甙  Example 1 Preparation of baicalin
取黄芩饮片 1000g, 加 10倍量水煎煮 2次, 合并煎出液, 过滤, 滤液待温度降至 40 时, 滴加浓盐酸调 pHl.O, 静止使沉淀, 弃去五 分之四的上清液, 加 5倍量蒸馆水使混悬, 滴加 40 %的氢氧化钠溶液调 ρΗ7.5 , 过滤, 在 0.1MP/cm2压力下超滤, 超波膜分子量截留值为 6000 - 20000, 将超滤液用浓盐酸调 pHl.O , 静止过滤, 沉淀用蒸馏水洗涤 3次, 抽滤, 干燥, 得黄芩总甙 70g . Take 1000g decoction of Scutellaria baicalensis and cook it twice with 10 times the amount of water. Combine the decoction and filter. When the temperature of the filtrate drops to 40, add concentrated hydrochloric acid dropwise to adjust the pH to 1.0, leave it to settle, and discard four-fifths. Supernatant, add 5 times the amount of distilled water to suspend, add 40% sodium hydroxide solution dropwise to adjust pH 7.5, filter, ultrafiltration at 0.1MP / cm 2 pressure, molecular weight cut-off value of the ultrasonic membrane is 6000 -20000, the ultra filtrate was adjusted to pH 1.0 with concentrated hydrochloric acid, statically filtered, the precipitate was washed 3 times with distilled water, filtered with suction, and dried to obtain 70 g of baicalin.
将上述黄芩总甙用乙醇重结晶, 得黄芩甙 58g . The above total baicalin was recrystallized from ethanol to obtain baicalin 58 g .
将所述的黄芩总甙或黄芩武在无菌条件下用注射用水混悬, 调 ρΗ-^.α o , 过滤、 浓缩、 干燥, 或将浓缩液倾入乙醇中使沉淀, 将沉淀 干燥, 即得注射用黄芩总甙或黄芩甙. Suspend the total glucosides of Scutellaria baicalensis or Scutellaria baicalensis with water for injection under sterile conditions, adjust ρΗ-^. Α o, filter, concentrate, dry, or pour the concentrated solution into ethanol to precipitate and precipitate Dry to obtain total baicalin or baicalin for injection.
实施例 2 制备金银花总有机酸  Example 2 Preparation of total organic acids of honeysuckle
取金银花药材或金银花叶 1000g , 用 12倍量的 60 %乙醇提取 2 - 4次, 减压回收溶剂, 加水制成含药材 100 %的水溶液, 然后用等量正 丁醇萃取, 从萃取液回收溶剂, 干燥即得金银花总有机酸 76g .  Take 1000g of honeysuckle medicinal material or honeysuckle leaf, extract 12 to 4 times with 12 times the amount of 60% ethanol, recover the solvent under reduced pressure, add water to make a 100% aqueous solution containing the medicinal material, and then extract with the same amount of n-butanol to recover from the extract Solvent, dried to obtain 76g of total honeysuckle organic acids.
从正丁醇萃取液回收溶剂至含药材量 100 %, 用等量 5 %碳酸氢钠 水溶液萃取 3次, 碱水液调 ρΗό.0-7.0, 滴加 3 %的明胶液使鞣质沉淀 完全, 静止, 过滤, 浓缩, 干燥, 即得除去鞣质及溶血性皂甙的总有机 酸 5 ; 或  The solvent was recovered from the n-butanol extract to 100% of the medicinal material, and extracted three times with an equivalent amount of 5% sodium bicarbonate aqueous solution. The alkaline aqueous solution was adjusted to pH 0-7.0, and the 3% gelatin solution was added dropwise to completely precipitate the tannin. , Standing, filtering, concentrating, and drying, so as to remove the total organic acids 5 of tannins and hemolytic saponins; or
取金银花药材或金银花叶 1000g , 用 12倍量的 60 %乙醇提取 2 - 4 次, 减压回收溶剂, 用大孔吸附树脂吸附, 用蒸馏水洗去杂质后, 用 乙醇洗脱, 即得除去鞣质及溶血性皂甙的金银花总有机 85g .  Take 1000g of honeysuckle medicinal material or honeysuckle leaf, extract 12 to 4 times with 12 times the amount of 60% ethanol, recover the solvent under reduced pressure, adsorb with macroporous adsorption resin, wash away impurities with distilled water, and elute with ethanol to remove tan. Honeysuckle and Organic Hemolytic Saponin 85g.
将上述金银花总有机酸 10g加至 1000g硅胶 G柱上, 用甲醇: 氯 仿 1: 1洗脱, 得到绿原酸 0.2g , 二咖啡酜奎宁酸 O.lg .  10 g of the above total honeysuckle organic acids were added to a 1000 g silica gel G column and eluted with methanol: chloroform 1: 1 to obtain 0.2 g of chlorogenic acid and dicaffeine quinic acid O.lg.
实施例 3 制备连 ¾总甙  Example 3 Preparation of total glycosides
取连翘药材或连翘叶 1000g,用 10倍量的 70 %乙醇提取 2 - 4次, 合并提取液, 减压回收溶剂, 制成含药材 100 %的提取物水溶液, 然后 用等量正丁醇萃取,从萃取液回收溶剂,浓缩,干燥即得连翘总甙 120g .  Take 1000g of Forsythia medicinal materials or forsythia leaves and extract them 2 to 4 times with 10 times the amount of 70% ethanol. Combine the extracts and recover the solvent under reduced pressure to make a 100% extract aqueous solution containing medicinal materials. Alcohol extraction, the solvent was recovered from the extract, concentrated and dried to obtain 120g of forsythia glycosides.
将上述连翘总甙用水溶解, 滴加 3 %的明胶液使鞣质沉淀完全, 静 止, 过滤, 滤液滴加饱和的胆甾醇乙醇液使皂武沉淀完全, 过滤, 滤液 浓缩, 干燥即得精制的除去鞣盾及溶血性皂甙的连翘总甙 95g ; 或  The total forsythiaside was dissolved in water, and 3% gelatin solution was added dropwise to complete the tannin precipitation, and the solution was filtered. The filtrate was added dropwise with a saturated cholesterol alcohol solution to complete the precipitation of saponin, filtered, and the filtrate was concentrated and dried to obtain a refined product. 95g of forsythia glycosides for removing tanning shield and hemolytic saponins; or
将上述连翘总甙 10g用水溶解, 用大孔吸附树脂 800g吸附, 用乙 醇洗脱, 即得精制的除去鞣质及溶血性皂甙的连翘总甙 6g .将该品用等 量硅胶拌匀,加于 600g硅胶 G柱上,用乙酸乙酯-丁 甲酸-水 5 : 3: 1 : 1洗脱, 得连翘醋甙 0.2g .  10g of the total forsythiaside was dissolved in water, 800g of the macroporous adsorption resin was used for adsorption, and eluted with ethanol to obtain 6g of forsythia total glycosides, which were purified to remove tannins and hemolytic saponins. , Added to a 600g silica gel G column, and eluted with ethyl acetate-butyric acid-water 5: 3: 1: 1: to obtain forsythiaside 0.2g.
实施例 4 气雾剂及制备方法  Example 4 aerosol and preparation method
黄芩总式 200g 连翘总甙 220g  Scutellaria Baicalensis Formula 200g Forsythia Suspension 220g
金银花总有机酸 180g 司盘 85 500g  Honeysuckle Total Organic Acid 180g Span 85 500g
油酸乙醋 500g 二氯二氟甲烷 适量  Ethyl oleate 500g dichlorodifluoromethane
制成 1000瓶, 每瓶 14g 制法: 按处方量将黄芩总甙、 金银花总有机酸. 连翘总甙粉碎, 过Made into 1000 bottles, 14g each Method: The total glucosides of Scutellaria Baicalensis and total organic acids of honeysuckle are crushed according to the prescribed amount.
80 - 120目筛, 然后与司盘 85、 油酸乙醋混匀, 研成糊状, 逐渐加至 胶体磨中, 以 1200rpm研至粒径为 10nm , 置容器中, 加阀门, 封帽, 压入二氯二氟甲烷至每瓶 14克, 摇勾, 即得气雾剂. 80-120 mesh sieve, then mix it with Span 85 and ethyl oleate, grind it into a paste, gradually add it to a colloid mill, grind it to a particle size of 10 nm at 1200 rpm, put it in a container, add a valve, and a cap. Press dichlorodifluoromethane to 14 grams per bottle and shake the hook to get an aerosol.
实施例 5栓剂及制备方法  Example 5 suppository and preparation method
黄芩总甙 180g 连翘总武 320g  Scutellaria Baicalensis 180g
金银花总有机酸 250g  Honeysuckle Total Organic Acid 250g
混合脂肪酸甘油醏( 34型) 750g  Mixed fatty acid glycerin tincture (type 34) 750g
制成 1000枚, 每枚 1.5g  1000 pieces, 1.5g each
制法: 按处方量将黄芩总甙、 金银花总有机酸、 连翘总甙粉碎, 过 80 - 120目筛, 混匀, 加入已加热熔化的栓剂基质中, 搅拌均匀, 注入 栓模中, 冷却、 切割、 包装、 即成栓剂.  Method: Crush the total glucosides of Scutellaria baicalensis, total organic acids of honeysuckle and total glycosides of forsythia, pass through 80-120 mesh sieve, mix well, add to the suppository base that has been heated and melted, stir well, inject into the suppository mold and cool , Cutting, packaging, serving as suppositories.
实施例 6含片及制备方法  Example 6: Tablets and preparation method
黄芩总甙 18g 连翘总甙 24g 金银花总有机酸 18g  Total Scutellaria Baicalensis 18g Total Forsythia Suspension 24g Total Honeysuckle Organic Acid 18g
环糊精 90g 糖粉 450g 薄荷脑 3g  Cyclodextrin 90g powdered sugar 450g menthol 3g
水片 lg 硬脂酸镁 6g  Water tablets lg magnesium stearate 6g
制成 1000片, 每片 0.6g  Made into 1000 tablets, 0.6g each
制法: 将黄芩总甙和环糊精包裹, 与连恝总戒、 金银花总有机酸、 糖粉混合均匀, 制成顆粒, 喷入薄荷脑、 冰片的乙醇液, 加入硬脂酸镁, 混匀, 压片, 即得含片.  Preparation method: Wrap total glucoside glycosides and cyclodextrin, mix with total cilantro ring, honeysuckle total organic acid, powdered sugar, make granules, spray into menthol and borneol ethanol solution, add magnesium stearate, mix Evenly, press the tablet to obtain a tablet.
实施例 7胶囊剂及制备方法  Example 7 Capsule and preparation method
黄芩总甙 18g 连恝总武 9g  Scutellaria Baicalensis 18g
金银花总有机酸 200g 丙烯酸树脂 适量  Honeysuckle total organic acid 200g acrylic resin
制成 1000粒, 每粒 0.25g  Made into 1000 capsules, each 0.25g
制法: 连翘总甙、 金银花总有机酸分别用干法制成顆粒, 用丙烯酸 树脂包薄膜衣, 并分别着不同瀕色, 与黄芩总甙颗粒混合, 装入空胶囊 中即得.  Production method: Forsythia total glycosides and honeysuckle total organic acids are made into granules by dry method, coated with acrylic resin film, and differently colored, mixed with baicalone total glycoside granules, and obtained in empty capsules.
实施例 8颗粒剂及制备方法  Example 8 Granules and preparation method
黄芩总甙 110g 连恝^甙 190g  Scutellaria Baicalensis Glycoside 110g Flatinol 190g
金银花总有机酸 4g 环糊精 6i、0g 制成 1000g , 每袋 4g 4 g total organic acids honeysuckle cyclodextrin 6i, 0g 1000g, 4g per bag
制法: 将黄芩总甙 110g用 690g环糊精包裹, 与连翘总甙、 金银花 总有机酸、 甜菊甙混合均匀, 制成颗粒.  Method: Wrapped 110g total glucosides with 690g cyclodextrin, mixed with forsythia total glycosides, honeysuckle total organic acids, stevioside and made into granules.
实施例 9 水针剂、 粉针剂及制备方法  Example 9 Water injection, powder injection and preparation method
黄芩总甙 18g 连翘总甙 29g  Scutellaria Baicalis 18g Forsythia Suspension 29g
金银花总有机酸 22g  Honeysuckle Total Organic Acid 22g
制成 1000ml或 100支(粉针剂)  Made into 1000ml or 100 sticks (powder injection)
制法: 将金银花总有机酸及连翘总甙用注射用水溶解, 调 pH5.0- 7.0, 过滤, 滴加 3 %的明胶液使鞣质沉淀完全, 静置, 过滤, 滤液滴加 饱和的胆 醇乙醇液使皂甙沉淀完全,过滤, 滤液加入黄芩总^使混悬, 用碳酸氢钠-碳酸钠液调 pH6. - .5使溶解, 经加热、 冷藏、 过滤、 超 滤等处理后, 灌封, 灭菌, 即 4注射液; 或浓缩, 干燥, 无菌分装, 即 得粉针剂.  Preparation method: Dissolve total organic acids of honeysuckle and total forsythia glycosides with water for injection, adjust pH 5.0-7.0, filter, and add 3% gelatin solution dropwise to complete tannin precipitation, let stand, filter, and add saturated filtrate The bile alcohol solution completely precipitated the saponin, filtered, and the filtrate was added to the total scutellaria baicalensis to suspend. The sodium bicarbonate-sodium carbonate solution was used to adjust the pH to 6.-.5 to dissolve. After heating, refrigerating, filtering, ultrafiltration, etc., Encapsulation, sterilization, that is, 4 injections; or concentrated, dry, sterile packaging, to obtain powder injection.
实施例 10 水针剂、 粉针剂及制备方法  Example 10 Water injection, powder injection and preparation method
黄芩总甙 15g  Scutellaria Baicalensis 15g
除去鞣质及溶血性皂武的连翘总甙 21g  Remove tannins and total forsythia glycosides 21g
除去鞣质及溶血性皂戒的金银花总有机酸 19g  Honeysuckle Total Organic Acids Removed Tannin and Hemolytic Soap Ring 19g
制成 100支  Made of 100
制法: 按处方量将精制的除去鞣质及溶血性皂甙的连翘总甙、 精制 的除去鞣质及溶血性皂式的金银花总有机酸用注射用水溶解, 加入黄芩 总武使混悬, 滴加碳酸氢钠 -瑗酸钠调 pH7.0-7.5使溶解, 经加热、 冷 藏、 过滤或超过滤处理后, 求封、 灭菌, 即得注射液; 或浓缩, 千燥, 无菌分装, 即得粉针剂.  Preparation method: According to the prescription amount, refined forsythia total glycosides for removing tannin and hemolytic saponin, refined organic acids for removing tannin and hemolytic soap type honeysuckle are dissolved with water for injection, and added to the scutellaria baicalensis for suspension Add sodium bicarbonate-sodium arsenate dropwise to adjust the pH to 7.0-7.5 to dissolve. After heating, refrigerating, filtering or ultrafiltration, seal and sterilize to obtain the injection solution; or concentrate, dry, and sterilize Installed to get powder injection.
实施例 11 粉针剂及制备方法  Example 11 Powder injection and preparation method
黄芩总甙 15g  Scutellaria Baicalensis 15g
除去鞣质及溶血性皂甙的连翹总武 21g  Forsythia Suspense 21g for removing tannins and hemolytic saponins
除去鞣质及溶血性皂甙的金银花总有机酸 19g  Honeysuckle Total Organic Acids Removed Tannin and Hemolytic Saponin 19g
制成 100支  Made of 100
制法: 按处方量将黄芩总武混悬于蒸馏水中, 用 40 %的氢氧化钠  Method: Suspension of Scutellaria baicalensis in distilled water according to the prescribed amount, with 40% sodium hydroxide
- 6 溶液调 pH7.0-8.0 , 浓缩; 干燥, 或加入乙醇, 使黃芩甙钠盐沉淀, 滤 除沉淀, 干燥, 粉碎, 即得注射用黄芩总甙盐原料; 将精制的除去鞣质 及溶血性皂甙的连翘总甙、 精制的除去鞣质及溶血性皂甙的金银花总有 机酸用注射用水溶解,滴加碳酸氢钠 -碳酸钠调 ρΗ7.0使溶解, 经加热、 冷藏、 过滤或超过滤处理后, 浓缩, 干燥, 粉碎, 在无茵条件下分装于 灭菌容器内, 再装入无菌的注射用黄芩总甙盐, 封口, 即得粉针剂; 或将上述三种成分分别测定含量, 在无菌条件下混合后无菌分装, 封口, 即得粉针剂. -6 The solution was adjusted to pH 7.0-8.0, concentrated; dried, or added with ethanol to precipitate the baicalin sodium salt, filtered off the precipitate, dried, and pulverized to obtain the baicalin total glucoside raw material for injection; the refined tannin and hemolytic properties were removed Total saponin forsythia glycosides, refined total organic acids of honeysuckle which remove tannins and hemolytic saponins are dissolved with water for injection. Sodium bicarbonate-sodium carbonate is adjusted to pH Η 7.0 to dissolve, and heated, refrigerated, filtered or ultra-filtered. After the treatment, it is concentrated, dried, and pulverized. It is divided into sterilized containers under sterile conditions, and then filled with sterile scutellaria baicalensis total glycosides, and sealed to obtain powder injections; or the above three components are measured separately. Content, aseptically aliquoted after mixing under aseptic conditions, and sealed to obtain a powder injection.
实施例 12 水针剂、 粉针剂及制备方法  Example 12 Water injection, powder injection and preparation method
黄芩甙 150g 连¾醏甙 200g  Baicalin 150g, Glucoside 200g
绿原酸 150g 二咖啡跣奎宁酸 25g  Chlorogenic acid 150g Dicaffeine Quinine 25g
制成 1000支  Made into 1,000
制法: 按处方量将黄芩甙混悬于蒸你水中, 用 40 %的氢氧化钠溶 液调 pH7.0-8.0, 浓缩, 干燥, 或加入乙醇, 使黄芩甙钠盐沉淀, 滤取 沉淀, 干燥, 粉碎, 即得注射用黄芩甙盐原料; 分别将绿原酸、 二咖啡 跣奎宁酸及连 ¾醏甙用注射用水溶解, 过滤, 滤液滴加碳酸氢钠碱液调 PH6.5-7.5 , 过滤, 浓缩, 干燥, 粉碎, 在无菌条件下分装于安瓿内, 然 后装入黄芩甙盐, 封口, 即得粉针剂.  Method: Suspend baicalin in distilled water according to the prescribed amount, adjust the pH to 7.0-8.0 with 40% sodium hydroxide solution, concentrate, dry, or add ethanol to precipitate the baicalin sodium salt, and filter the precipitate. Dry and pulverize to obtain the baicalin salt material for injection. Dissolve chlorogenic acid, dicaffeine quinic acid and dihydrogenin in water for injection, filter, and drop the filtrate to adjust the pH 6.5- 7.5, filter, concentrate, dry, pulverize, distribute into ampoules under sterile conditions, then load the baicalin salt, and seal to obtain the powder injection.
实施例 13 口服液及制备方法  Example 13 Oral liquid and preparation method
黄芩总甙 200g 连翘总甙 0.8g  Total glucosides of baicale 200g Total glycosides of forsythia 0.8g
金银花总有机酸 80g 白砂糖 80g  Honeysuckle Total Organic Acid 80g White Granulated Sugar 80g
碳酸钠 -碳酸氢钠緩冲液适量  Sodium carbonate-sodium bicarbonate buffer
制成 1000ml  Made into 1000ml
制法: 按处方量将连翘总甙、 金银花总有机酸、 黄芩总甙用緩冲液 溶解, 过滤、 灌封、 灭菌、 即得口服液.  Method: Dissolve total forsythia glucosides, total honeysuckle organic acids, and baicalone total glucosides in buffer according to the prescribed amount, filter, pot, sterilize, and obtain oral solution.
实施例 14 水针剂及制备方法  Example 14 Water injection and preparation method
注射用黄芩总甙 200g  Total baicalin for injection 200g
除去鞣质及溶血性皂甙的连翘总甙 3.7g  Forsythia glycosides tannins and hemolytic saponins removed 3.7g
制成 1000ml  Made into 1000ml
制法: 将除去鞣质及溶血性皂甙的 ¾总甙用注射 水溶解, 加入 注射用黄芩总甙, 用碳酸 -氢钠溶液调 pH6.5-7.5, 经加热, 冷藏等常规 处理后, 灌封, 灭菌, 即得水针剂. Preparation method: Dissolve ¾ total glycosides from which tannins and hemolytic saponins are removed, and add The total glucosides of baicale for injection were adjusted to pH 6.5-7.5 with a sodium bicarbonate solution. After conventional processing such as heating, refrigerating, potting and sterilization, water injection was obtained.
实施例 15粉针剂及制备方法  Example 15 powder injection and preparation method
注射用黄芩总甙 3.7g  Total Baicalin for injection 3.7g
除去鞣质及溶血性皂甙的连翘总甙 200g Forsythia glycosides with tannins and hemolytic saponins removed 200 g
制成 100支  Made of 100
制法: 按处方量将精制的除去鞣质及溶血性皂甙的连翘总武用注射 用水溶解, 滴加碳酸氢钠溶液调 pH6.5-7.5 , 经常规处理后, 干燥, 粉 碎, 在无菌条件下分装于灭菌容器内, 再装入注射用黄芩总甙, 封口, 即得粉针剂.  Method: Dissolve the refined Forsythia suspensa with water for injection to remove tannin and hemolytic saponin according to the prescribed amount, add sodium bicarbonate solution dropwise to adjust pH 6.5-7.5, after conventional treatment, dry, pulverize, Under bacterial conditions, aliquot it into a sterilized container, and then fill it with total baicalin for injection and seal it to obtain a powder injection.
实施例 16粉针剂及制备方法  Example 16 Powder injection and preparation method
注射用黄芩总甙 200g  Total baicalin for injection 200g
除去鞣质及溶血性皂甙的连翘醋甙 300g  Forsythiaside 300g for removing tannins and hemolytic saponins
制成 100支  Made of 100
制法: 按处方量将精制的除去鞣质及溶血性皂甙的连翘总甙用注射 用水溶解, 滴加碳酸氢钠溶液调 pH6.5-7.5, 经常规处理后, 干燥, 粉 碎, 在无菌条件下分装于灭菌容器内, 再装入注射用黄芩总^, 封口, 即得粉针剂.  Preparation method: Dissolve refined forsythia total glycosides for removing tannin and hemolytic saponin with water for injection, add sodium bicarbonate solution dropwise to adjust pH 6.5-7.5, after conventional treatment, dry, crush, and Under bacterial conditions, aliquoted into a sterilized container, and then filled with Scutellaria baicalensis for injection, sealed, to obtain a powder injection.
本发明的药物组合物经药效学试验证明, 抗菌作用优于双黄连制 剂, 抗合抱病毒作用与双黄连制剂相似, 试验结果如下:  The pharmacodynamic test of the pharmaceutical composition of the present invention proves that the antibacterial effect is better than that of Shuanghuanglian preparation, and the anti-embedging virus effect is similar to that of Shuanghuanglian preparation. The test results are as follows:
1、 抗菌作用:  1. Antibacterial effect:
试管内抗菌试验证明, 本发明所述的组合物具有较强的抗菌作用, 对链球菌 A群、 肺炎双球菌、 流感杆菌、 痢疾杆菌、 绿脓杆菌抗菌作用 比双黄连制剂高 1 - 2个稀释度. 实验结果见表 1 、 2 .  The in-tube antibacterial test proves that the composition of the present invention has a strong antibacterial effect, and has an antibacterial effect on Streptococcus group A, pneumococcus, influenzae bacillus, dysentery bacillus, and Pseudomonas aeruginosa, which are 1 to 2 higher than the Shuanghuanglian preparation. Dilution. The experimental results are shown in Tables 1 and 2.
表 1 双黄连制剂抗菌试验结果  Table 1 Antibacterial test results of Shuanghuanglian preparation
试管编号 1 2 3 4 5 6 7 8 9 10 稀释度 1:4 1:8 1:16 1:32 1:64 1:128 1:256 1:512 1:1024 0 葡萄球菌 - - - - - - - + + + 链球菌 - - - + + + + + + + 肺炎球 ¾ 一 - + + + + -4- + + 白喉杆菌 - - - - - + + + + + + 流感杆菌 + + + + + + + + + + 大肠杆菌 - - - - + + + + + + 绿脓杆菌 ― - - + + + + + + + 芽孢杆菌 + + + + 痢疾杆菌 - + + + + + + + + + 表 2 本发明药物组合物抗菌实验结果 Test tube number 1 2 3 4 5 6 7 8 9 10 Dilution 1: 4 1: 8 1:16 1:32 1:64 1: 128 1: 256 1: 512 1: 1024 0 Staphylococcus------ -+ + + Streptococcus---+ + + + + + + Pneumococcal ¾ a-+ + + + -4- + + Diphtheria-----+ + + + + + + Influenza + + + + + + + + + + E. Coli----+ + + + + + Pseudomonas Aeruginosa---+ + + + + + + Bacillus + + + + Shigella-+ + + + + + + + + Table 2 Antibacterial test results of the pharmaceutical composition of the present invention
试管编号 1 2 3 4 5 6 7 8 9 10 稀释度 1:4 1:8 1:16 1:32 1:64 1:128 1:256 1 :512 1 :1024 0 葡萄球菌 + + + 链球菌 - - - 一 + + + + + + 肺炎球菌 - - 一 — + + + + + + 白喉杆菌 - - - - + + + + + + 流感杆菌 - 一 + + + + + + + + 大肠杆菌 - - - - + + + + + + 绿脓杆菌 - - - 一 + + + + + + 芽孢杆菌 + + + + 痢疾杆菌 - + + + + + + + + + Test tube number 1 2 3 4 5 6 7 8 9 10 Dilution 1: 4 1: 8 1:16 1:32 1:64 1: 128 1: 256 1: 512 1: 1024 0 Staphylococcus + + + + Streptococcus- --One + + + + + + Pneumococcus--One + + + + + + Diphtheria----+ + + + + Influenza-One + + + + + + + + E. coli--- -+ + + + + + Pseudomonas aeruginosa----+ + + + + + Bacillus + + + + Shigella-+ + + + + + + +
2、 抗病毒作用:  2. Antiviral effect:
用细抱组织培养法观察其抗呼吸道合胞病毒的作用, 结果证明, 本 发明所述的药物組合物具有显著的抗病毒作用, 其作用强度与双黄连制 剂相似. 结果见表 3 .  The fine-tissue tissue culture method was used to observe its anti-respiratory syncytial virus effect, and the results proved that the pharmaceutical composition of the present invention has a significant anti-viral effect, and its intensity of action is similar to that of the Shuanghuanglian preparation. The results are shown in Table 3.
表 3 抗合! &病毒作用实验观察  Table 3 Anti-combination! & Experimental observation of viral effects
稀释 10 1 10-2 500X 10'3 5仟 Χ ΚΓ 5万 X空白 病变 双黄连制剂 100% 25% - - - - - - 本发明 100% 25% Dilute 10 1 10- 2 500X 10 ' 3 5 仟 × ΚΓ 50,000 X blank lesion Shuanghuanglian preparation 100% 25%------The present invention 100% 25%
程度 对照组 75% 75% 75% 50% 50% 25% - -Degree Control group 75% 75% 75% 50% 50% 25%--
3 . 含有黄芩总武及连翘总甙, 不含金银花总有机^的药物组合物 抗菌作用稍有减弱, 其中对白喉杆菌、 芽孢杆菌的抗菌作 -t.含有金银 花总有机酸的药物组合物相似, 对其它菌株的抗菌作用低一个稀释度; 抗合胞病毒作用相近. ' 3. The pharmaceutical composition containing total scutellaria baicalensis and total forsythia glycosides and no total organic honeysuckle ^ has a slight weakened antibacterial effect, among which antibacterial action against diphtheria and bacillus -t. Contains gold and silver The pharmaceutical composition of total organic acids in flowers is similar, and the antibacterial effect on other strains is one dilution lower; the anti-syncytial virus effect is similar.

Claims

权 利 要 求 Rights request
1. 一种抗菌抗病毒药物组合物,该组合物含有 0.02-98.18%从黄芩中 提取的黄芩总甙, 0.02-98.18%从连 ¾或连翘叶中提取的连翘总甙, 选 择性地含有 0.40-88.18%从金银花或金银花叶中提取的金银花总有机酸 作为活性成分, 以及选择性地含有药用赋形剂. 1. An antibacterial and antiviral pharmaceutical composition comprising 0.02-98.18% of total glucosides of baicalein extracted from scutellaria baicalensis and 0.02-98.18% of total glycosides of forsythia radix from forsythia or forsythia leaves Contains 0.40-88.18% of the total organic acids of honeysuckle extracted from honeysuckle or honeysuckle leaves as active ingredients, and optionally contains pharmaceutical excipients.
2. 根据权利要求 1所述的抗菌抗病毒药物组合物, 其特征在于所述 的活性成分中, 制备口服制剂、 栓剂、 气雾剂时, 黄芩总甙中含黄芩甙 >70%, 连翘总甙中含连翘癬甙>10°/。, 金银花总有机酸中含绿原酸 >10%; 制备注射剂时, 黄芩总甙中含黄芩甙 >86%, 连翘总式中含连翘 醋甙 >25%, 金银花总有机酸中含绿原酸 >25%.  2. The antibacterial and antiviral pharmaceutical composition according to claim 1, characterized in that when the oral ingredients, suppositories and aerosols are prepared in the active ingredient, the baicalin glycosides contain baicalin> 70%, forsythia The total glycosides contain forsythiaside> 10 ° /. , Total organic acids in honeysuckle contain chlorogenic acid> 10%; In the preparation of injection, total baicalin contains baicalin> 86%, forsythia total formula contains forsythiaside glycosides> 25%, total honeysuckle organic acid contains green Orthoacid> 25%.
3. 制备如权利要求 1或 2所述的抗苗抗病毒药物组合物的方法, 该 方法包括下列步骤:  3. A method for preparing an anti-vaccine antiviral pharmaceutical composition according to claim 1 or 2, the method comprising the following steps:
( i )制备活性成分:  (i) Preparation of active ingredients:
( a )制备黄芩总甙: 按常规方法从黄芩制备口服用的黄芩总甙或 黄芩甙; 或再将所得黄芩总甙或黄芩甙在无菌条件下用注射用水混悬, 调 pH7.0-8.0, 过滤、 浓缩、 干燥; 或将浓缩液倾入乙醇中使沉淀, 将 沉淀干燥, 即得注射用黄芩总甙或黄芩^;  (a) Preparation of baicalin glycosides: According to the conventional method, baicalin baicalin or baicalin is prepared for oral use; or the obtained baicalin baicalin or baicalin is suspended in water for injection under sterile conditions, and the pH is adjusted to 7.0- 8.0, filtering, concentrating, drying; or pouring the concentrated solution into ethanol to precipitate, and drying the precipitate, that is to obtain total baicalin or baicalein for injection ^;
( b )制备连翘总甙:  (b) Preparation of total forsythiaside:
取连翘或连 ¾叶, 按常规方法提取, 浓缩后用正丁醇等有机溶剂萃 取, 经常规处理得口服剂、 气雾剂、 栓剂等用连 ¾总武; 将上述连翘总 甙用水溶解, 滴加 1 - 15 %明胶液、蛋清液或其它沉淀剂使鞣质沉淀完 全, 静置, 过滤, 滤液滴加饱和的胆 醇乙醇液或其它沉淀剂使皂甙沉 淀完全, 经常规处理, 即得精制的除去鞣质及溶血性皂甙的连翘总甙; 或者, 取连翘或连 ¾叶, 按常规方法提取, 提取液用聚跣胺、 大孔 吸附树脂、 硅胶等吸附剂吸附, 洗去杂质后, 用水、 乙醇、 丙鲖、 乙酸 乙醋等溶剂洗脱, 即得除去鞣盾及溶血性皂武的连翘酯甙;  Take forsythia or forsythia leaves, extract them according to conventional methods, and concentrate them with organic solvents such as n-butanol. After conventional treatment, forsythia can be used in oral preparations, aerosols, suppositories, etc .; Dissolve, add 1-15% gelatin solution, egg white solution or other precipitants dropwise to complete the tannin precipitation, let it stand, filter, and add the saturated bile alcohol solution or other precipitants dropwise to complete the precipitation of saponins. After conventional treatment, That is to obtain refined forsythia glycosides that remove tannins and hemolytic saponins; or, take forsythia or forsythia leaves and extract them according to conventional methods, and extract the solution with adsorbents such as polyamine, macroporous adsorption resin, silica gel, etc. After the impurities are washed away, the solvents such as water, ethanol, propidium, ethyl acetate and the like are used to elute the tannin and hemolytic saponin.
需要的话, ( c )制备金银花总有机酸:  If necessary, (c) Preparation of total organic acids of honeysuckle:
取金银花或叶, 按常规方法提取, 浓缩后用正丁醇等有机溶剂萃 取, 经常规处理, 即得口服制剂、 气雾剂、 栓剂用原料; 上述正丁醇萃 取液用碳酸氢钠 -磷酸氢钠或 pH7.0~8.0的緩冲液萃取, 萃取液调 ρΗ5.0~7.0 , 滴加 1 ~ 15 %的明胶液、 蛋清液或其它沉淀剂使鞣质沉淀 完全, 经常规处理, 即得除去鞣质及溶血性皂武的金银花总有机酸; 或者, 取金银花或叶, 按常规方法提取, 提取液用聚酰胺、 大孔吸 附树脂、 硅胶等吸附剂吸附, 洗去杂质后, 用水、 碱水、 乙醇、 丙 ^等 溶剂洗脱, 即得除去鞣质及溶血性皂甙的金银花总有机酸; Take honeysuckle or leaves, extract them by conventional methods, and concentrate them with organic solvents such as n-butanol Take, after conventional processing, to obtain raw materials for oral preparations, aerosols, suppositories; the above-mentioned n-butanol extract is extracted with sodium bicarbonate-sodium hydrogen phosphate or a buffer solution of pH 7.0 ~ 8.0, the extract is adjusted ρΗ5. 0 ~ 7.0, add 1 ~ 15% of gelatin solution, egg white solution or other precipitant dropwise to complete the tannin precipitation, and after conventional treatment, the total organic acids of honeysuckle of tannin and hemolytic soap can be removed; or, take the honeysuckle Or leaves, extracted according to conventional methods, the extract is adsorbed with an adsorbent such as polyamide, macroporous adsorption resin, silica gel, etc. After the impurities are washed away, the solvent is eluted with water, alkaline water, ethanol, propylene, etc. Total organic acids of honeysuckle with hemolytic saponins;
需要的话, ( ii )将上述活性成分与賦形剂混合.  If necessary, (ii) mix the above active ingredients with excipients.
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