WO2024082330A1 - 一种龙血竭的提取方法 - Google Patents
一种龙血竭的提取方法 Download PDFInfo
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- WO2024082330A1 WO2024082330A1 PCT/CN2022/127872 CN2022127872W WO2024082330A1 WO 2024082330 A1 WO2024082330 A1 WO 2024082330A1 CN 2022127872 W CN2022127872 W CN 2022127872W WO 2024082330 A1 WO2024082330 A1 WO 2024082330A1
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Classifications
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Definitions
- the invention belongs to the field of natural plant component extraction and discloses a method for extracting dragon's blood.
- Dragon’s blood Latin name resina draconis. is the resin of the sword-leaved dragon tree of the Liliaceae family, mainly distributed in Yunnan, my country and Southeast Asian countries. When the bark is cut, a deep red juice will flow out, like human blood.
- the main component is dragon’s blood B, which has a slight fragrance and a light and slightly astringent taste. It has the effects of promoting blood circulation and dispersing blood stasis, relieving pain and stopping bleeding, and healing sores and promoting tissue regeneration. It is suitable for traumatic injuries, pain caused by blood stasis, and traumatic bleeding.
- dragon’s blood produced in China is significantly similar to that of dragon’s blood, a resin plant of the genus Dracaena in the Agave family from West Asia and North Africa. Both contain chemical components such as chalcones, polychalcone, flavanoids, homoisoflavanoids, chromones, flavonoids, simple phenols, steroidal saponins, triterpenes, fatty alcohols and their esters.
- ethanol is mostly used for extracting dragon's blood, and the obtained extract is mainly used to inhibit venous thrombosis, inhibit focal cerebral ischemia, treat ischemic brain edema, etc., such as the Chinese invention patent with application number 02129688.X "A preparation process of dragon's blood total flavonoids and its new use".
- the preparation process is to crush the dragon's blood medicinal material into coarse powder, add ethyl acetate for reflux extraction, filter, recover ethyl acetate and concentrate to dryness;
- CN201310428409.9 dragon's blood extract preparation method and use and lotion including the following steps: take dragon's blood raw medicinal material, add 3 to 9 times the weight of organic solvent for reflux extraction, concentrate, dry, and obtain dragon's blood extract.
- the preparation method of CN86108273 dragon's blood provides a new alkali extraction method, which is to add the raw material into the extraction tank, use a certain amount of dilute alkali solution for extraction at room temperature or heating for a certain time, filter out the alkali extract, add acid for neutralization and filtration, and add ethanol solution to dissolve the precipitate, filter or centrifuge. The dissolved liquid is concentrated and ethanol is recovered, and the concentrated liquid is dried to obtain the product. Its characteristic is that organic solvents such as ethyl acetate and ethanol are saved. However, there is a large gap in appearance and internal quality between the dragon's blood prepared by the above-mentioned alkali extraction process and the dragon's blood prepared by the alcohol extraction process. If it is to replace the alcohol extraction process, it still needs further improvement.
- the present invention discloses a method for extracting dragon's blood and application thereof.
- a method for extracting dragon's blood comprises the following steps:
- Leaching and impurity removal soak in deionized water for 2-4 hours, remove impurities with the aid of ultrasonic wave, filter, add the filter cake into the leaching solution for leaching, heat to 40-50°C, soak for 1-2 hours, remove free sugar and fat; then filter the residue through gauze, wash with deionized water, dry, grind and pass through a 100-200 mesh sieve to obtain raw material B;
- Supercritical extraction Use an extraction solvent to perform supercritical extraction of raw material B, the extraction pressure is 35-45MPa, the temperature is 55-65°C, the extraction time is 30-40min, and the extraction solvent flow rate is 10-20kg/h; the analysis process of the extraction effluent is three-stage, the first stage analysis pressure is 15-20MPa, the analysis temperature is 50-60°C, the second stage analysis pressure is 6-12MPa, the analysis temperature is 40-50°C, the third stage analysis pressure is 2-3.5MPa, and the analysis temperature is 30-40°C.
- the extraction part is discarded and the extraction residue is collected, which is raw material C;
- Vacuum drying placing the raw material E in a vacuum drying oven and vacuum drying at low temperature until the water content is less than 10%, thereby obtaining raw material F;
- Prefreezing Spread the raw material F flat to a thickness of less than 1 cm, put it into a freezing device, and quickly cool it to below -30°C at a cooling rate of 5-8°C/min to obtain raw material G;
- Freeze drying Add a freeze drying protective agent with a final content of 5-10 wt% to the raw material G, mix evenly, put it into a freeze dryer for freeze drying, and perform the following A-D freeze drying cycle 2-4 times to obtain raw material H:
- A -35 ⁇ -45°C, pressure 1000-2000Pa, freeze drying 30-60min;
- Vacuum packaging slowly heat the raw material H to room temperature to obtain the dragon's blood extract, and vacuum package it.
- pretreatment and leaching are used to remove impurities, so that most of the free sugars and impure lipids can be removed, which is convenient for post-treatment and purification of the final product.
- the present invention uses supercritical extraction, selects a suitable extraction solvent, and combines with an alkali extraction method to extract the effective component of dragon's blood, mainly dragon's blood B, with maximum retention, and reduces the amount of organic solvent used in the alcohol extraction method.
- a vacuum drying procedure is used to dry and preserve the dragon's blood effective component dragon's blood B, which is convenient for use as a pharmaceutical raw material.
- the leaching solution in step 2) is 30% by weight ethanol.
- the leaching solution in step 2) comprises 0.5-1 parts of hydrochloric acid, 2-4 parts of ethanol and 10 parts of water by weight. Compared with the simple ethanol leaching solution, the above-mentioned leaching solution has a higher content of dragon's blood B.
- the extraction solvent in step 3 is ethyl acetate.
- the extraction solvent in step 3) comprises 1-2 parts of tetraethylene glycol ether, 2-3 parts of trichloroethylene, and 10 parts of ethyl acetate by weight. Compared with the traditional ethyl acetate, the above-mentioned extraction solvent can obtain a higher content of dragon's blood B.
- the parameters of low-temperature vacuum drying are 40-50°C and the pressure is less than 133Pa.
- the freeze-drying protective agent is glycerol.
- the freeze-drying protective agent is modified trehalose, and the modified trehalose is modified by the following steps:
- the final yield of dragon's blood is higher than that using glycerol.
- the use of the dragon's blood extract in the preparation of a drug for treating allergic rhinitis is a nasal spray, each spray containing 100-200 ⁇ g of the dragon's blood extract.
- the traditional nasal spray with 100-200 ⁇ g of the dragon's blood extract added per spray has significantly better quality and effect for allergic rhinitis.
- the present invention has the following beneficial effects:
- the invention discloses a method for extracting dragon's blood and its application.
- the invention uses pretreatment and leaching to remove impurities, which can remove most of the free sugars and impurity lipids, facilitate post-treatment, and purification of the final product.
- the invention uses supercritical extraction, selects a suitable extraction solvent, and combines with an alkali extraction method to extract the effective component of dragon's blood, mainly dragon's blood B, to the maximum extent, and reduces the amount of organic solvent used in the alcohol extraction method. Finally, a vacuum drying procedure is used to dry and preserve the dragon's blood effective component dragon's blood B, which is convenient for the use of drug raw materials.
- the invention uses a customized leaching solution and extraction solvent compared with a simple ethanol leaching solution and an ethyl acetate extraction solvent, and the content of dragon's blood B obtained is higher; using a customized modified trehalose as a protective agent, the obtained dragon's blood yield is higher.
- the invention also discloses the application of the dragon's blood effective component mainly dragon's blood B, and the traditional nasal spray with 100-200 ⁇ g of the dragon's blood added to each spray has a significantly better quality effect on allergic rhinitis.
- the dragon's blood extraction method disclosed in the present invention uses less organic solvent, has mild extraction conditions, retains more natural components, and has less impurity content in the obtained extract. It is also found that the dragon's blood extract obtained by the extraction method disclosed in the present invention also has a good effect on the treatment of allergic rhinitis, can be added as an effective ingredient in traditional anti-allergic drugs to play a synergistic effect, and the extract is a pure natural substance with little toxic and side effects.
- Fig. 1 is a flow chart of extraction of dragon's blood according to the present invention
- FIG2 is a comparison chart of the yield (%) of dragon's blood extract in Test Example 1;
- FIG3 is a comparison chart of the content (%) of Loureirin B in Test Example 1;
- FIG4 is the absolute amount (mg) of Loureirin B in Test Example 1;
- FIG. 5 is a comparison diagram of the treatment effects before and after treatment in Test Example 2.
- the reagents or instruments used in the examples of the present invention without indicating the manufacturer are all conventional reagent products that can be obtained through commercial purchase.
- a method for extracting dragon's blood comprises the following steps:
- Leaching and impurity removal soak in deionized water for 2 hours, remove impurities with the aid of ultrasonic wave, filter, add the filter cake into the leaching solution for leaching, heat to 40°C, soak for 1 hour, remove free sugar and fat; then filter the residue through gauze, wash with deionized water, dry, grind and pass through a 100-mesh sieve to obtain raw material B;
- Supercritical extraction Use an extraction solvent to perform supercritical extraction of raw material B, the extraction pressure is 35MPa, the temperature is 55°C, the extraction time is 30min, and the extraction solvent flow rate is 10kg/h; the analysis process of the extraction effluent is three-stage, the first stage analysis pressure is 15MPa, the analysis temperature is 50°C, the second stage analysis pressure is 6MPa, the analysis temperature is 40°C, the third stage analysis pressure is 2MPa, and the analysis temperature is 30°C. The extracted part is discarded and the extraction residue is collected, which is raw material C;
- Vacuum drying placing the raw material E in a vacuum drying oven and vacuum drying at low temperature until the water content is less than 10%, thereby obtaining raw material F;
- Prefreezing Spread the raw material F flat to a thickness of less than 1 cm, put it into a freezing device, and quickly cool it to below -30°C at a cooling rate of 5-8°C/min to obtain raw material G;
- Freeze drying Add a freeze drying protective agent with a final content of 5 wt% to the raw material G, mix evenly, put it into a freeze dryer for freeze drying, and perform the following A-D freeze drying cycle twice to obtain raw material H:
- Vacuum packaging slowly heating the raw material H to room temperature to obtain the dragon's blood extract, and vacuum packaging;
- the leaching solution in step 2) comprises 0.5 parts of hydrochloric acid, 2 parts of ethanol and 10 parts of water by weight.
- the extraction solvent in step 3) comprises 1 part of tetraethylene glycol ether, 2 parts of trichloroethylene and 10 parts of ethyl acetate by weight.
- the parameters of low-temperature vacuum drying are 40° C. and the pressure is less than 133 Pa.
- the freeze drying protective agent is modified trehalose, and the modified trehalose is modified by the following steps:
- a method for extracting dragon's blood comprises the following steps:
- Leaching and impurity removal soak in deionized water for 2-4 hours, remove impurities with the aid of ultrasonic wave, filter, add the filter cake into the leaching solution for leaching, heat to 45°C, soak for 1.5 hours, remove free sugar and fat; then filter the residue through gauze, wash with deionized water, dry, grind and pass through a 100-200 mesh sieve to obtain raw material B;
- Supercritical extraction Use an extraction solvent to perform supercritical extraction of raw material B, the extraction pressure is 40MPa, the temperature is 60°C, the extraction time is 35min, and the extraction solvent flow rate is 15kg/h; the analysis process of the extraction effluent is three-stage, the first stage analysis pressure is 18MPa, the analysis temperature is 55°C, the second stage analysis pressure is 9MPa, the analysis temperature is 45°C, the third stage analysis pressure is 3MPa, and the analysis temperature is 35°C.
- the extraction part is discarded and the extraction residue is collected, which is raw material C;
- Vacuum drying placing the raw material E in a vacuum drying oven and vacuum drying at low temperature until the water content is less than 10%, thereby obtaining raw material F;
- Prefreezing Spread the raw material F flat to a thickness of less than 1 cm, put it into a freezing device, and quickly cool it to below -30°C at a cooling rate of 5-8°C/min to obtain raw material G;
- Freeze drying Add a freeze drying protective agent with a final content of 8 wt% to the raw material G, mix evenly, put it into a freeze dryer for freeze drying, and perform the following A-D freeze drying cycle 3 to obtain raw material H:
- Vacuum packaging slowly heating the raw material H to room temperature to obtain the dragon's blood extract, and vacuum packaging;
- the leaching solution in step 2) comprises, by weight, 0.75 parts of hydrochloric acid, 3 parts of ethanol and 10 parts of water.
- the extraction solvent in step 3) comprises 1.5 parts of tetraethylene glycol ether, 2.5 parts of trichloroethylene and 10 parts of ethyl acetate by weight.
- the parameters of low-temperature vacuum drying are 45° C. and the pressure is less than 133 Pa.
- the freeze drying protective agent is modified trehalose, and the modified trehalose is modified by the following steps:
- a method for extracting dragon's blood comprises the following steps:
- Leaching and impurity removal soak in deionized water for 3 hours, remove impurities with the aid of ultrasonic wave, filter, add the filter cake into the leaching solution for leaching, heat to 50°C, soak for 1.5 hours, remove free sugar and fat; then filter the residue through gauze, wash with deionized water, dry, grind and pass through a 150-mesh sieve to obtain raw material B;
- Supercritical extraction Use an extraction solvent to perform supercritical extraction of raw material B, the extraction pressure is 45MPa, the temperature is 65°C, the extraction time is 40min, and the extraction solvent flow rate is 20kg/h; the analysis process of the extraction effluent is three-stage, the first stage analysis pressure is 20MPa, the analysis temperature is 60°C, the second stage analysis pressure is 12MPa, the analysis temperature is 50°C, the third stage analysis pressure is 3.5MPa, and the analysis temperature is 40°C. The extracted part is discarded and the extraction residue is collected, which is raw material C;
- the obtained raw material C was mixed with 6wt% NaOH solution at a mass ratio of 1:20, and then put into a reaction kettle, and extracted at a pressure of 10Mpa and 60°C for 3h, and extracted 4 times, and the extracts were combined to obtain raw material D;
- Vacuum drying placing the raw material E in a vacuum drying oven and vacuum drying at low temperature until the water content is less than 10%, thereby obtaining raw material F;
- Prefreezing Spread the raw material F flat to a thickness of less than 1 cm, put it into a freezing device, and quickly cool it to below -30°C at a cooling rate of 5-8°C/min to obtain raw material G;
- Freeze drying Add a freeze drying protective agent with a final content of 10 wt% to the raw material G, mix evenly, put it into a freeze dryer for freeze drying, and perform the following A-D freeze drying cycle 4 times to obtain raw material H:
- Vacuum packaging slowly heating the raw material H to room temperature to obtain the dragon's blood extract, and vacuum packaging;
- the leaching solution in step 2) comprises, by weight, 1 part of hydrochloric acid, 4 parts of ethanol and 10 parts of water.
- the extraction solvent in step 3) comprises 2 parts of tetraethylene glycol ether, 3 parts of trichloroethylene and 10 parts of ethyl acetate by weight.
- the parameters of low-temperature vacuum drying are 50° C. and the pressure is less than 133 Pa.
- the freeze drying protective agent is modified trehalose, and the modified trehalose is modified by the following steps:
- a method for extracting dragon's blood wherein the leaching solution in step 2) is 30% by weight ethanol, and the rest is the same as in embodiment 2.
- a method for extracting dragon's blood wherein the extraction solvent in step 3) is ethyl acetate, and the rest is the same as in Example 2.
- step 8 A method for extracting dragon's blood, in step 8), the freeze-drying protective agent is glycerol, and the rest is the same as in Example 2.
- the dragon's blood extracts obtained by the extraction of Examples 1-3 and Comparative Examples 1-3 were compared in terms of the yield (final mass after freeze-drying/raw material amount) of the dragon's blood extracts obtained, as well as the content and absolute amount of dragon's blood B therein.
- the content of dragon's blood B was detected by HPLC, and the chromatographic conditions were as follows:
- Detection wavelength 260nm
- Injection volume 10 ⁇ L
- a nasal spray is prepared from a dragon's blood extract and excipients, wherein the dragon's blood extract is prepared by the method of Example 2, and the excipients contain glucose, microcrystalline cellulose and sodium carboxymethyl cellulose, phenylethyl alcohol, preservative benzalkonium chloride, Tween 80, dilute hydrochloric acid and pure water (i.e., the excipient trade name of the existing fluticasone propionate nasal spray: Fu Shuliang); each spray contains 150 ⁇ g of the dragon's blood extract.
- a nasal spray namely the existing fluticasone propionate nasal spray, trade name: Fu Shuliang; each spray contains 50 ⁇ g of fluticasone propionate.
- a nasal spray wherein a dragon's blood extract and fluticasone propionate are dissolved in the nasal spray, wherein the dragon's blood extract is prepared by the method of Example 2, and the auxiliary materials include glucose, microcrystalline cellulose and sodium carboxymethyl cellulose, phenylethyl alcohol, preservative benzalkonium chloride, Tween 80, dilute hydrochloric acid and pure water (i.e., the auxiliary material trade name of the existing fluticasone propionate nasal spray: Fu Shuliang); each spray contains 150 ⁇ g of dragon's blood extract and 50 ⁇ g of fluticasone propionate.
- the nasal sprays prepared in Examples 4-6 were applied to patients with allergic rhinitis. 160 patients were randomly divided into 4 groups, 30 in each group. The nasal sprays of Examples 4-6 and the negative control (spray containing only excipients) were applied respectively, once in the morning and evening every day. After one day of treatment, the scores were given according to the efficacy evaluation table in Table 2, and the total score was calculated for each group to obtain the treatment effect table in Table 3 and Figure 5.
- the dragon's blood extract prepared by the present invention has a certain effect of treating allergic rhinitis, but it does not reach the effect of the traditional western medicine fluticasone propionate.
- the use of fluticasone propionate alone can achieve a therapeutic effect of 96, but after the dragon's blood extract and the western medicine fluticasone propionate are used together, the therapeutic effect can be improved to more than 120, which proves that the dragon's blood extract and the western medicine fluticasone propionate have a good synergistic effect in treating allergic rhinitis. It has a good market prospect.
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Abstract
一种龙血竭的提取方法，属于天然植物成分提取领域，包括以下步骤：1)前处理、2)浸出除杂、3)超临界萃取、4)碱提、5)旋转蒸发、6)真空干燥、7)预冻、8)冷冻干燥、9)真空包装；所述龙血竭的提取方法相比现有技术，有机溶剂的使用量少，提取条件温和，保留天然成分多，获得的提取物中杂质含量少，并且所述提取方法提取获得的龙血竭提取物对于过敏性鼻炎的治疗也具有良好的效果，可以作为有效成分添加到传统的抗过敏药物中，发挥协同增效作用，并且所述提取物为纯天然物质，毒副作用小。
Description
本发明属于天然植物成分提取领域，公开了一种龙血竭的提取方法。
龙血竭，拉丁文名resina draconis.为百合科剑叶龙血树的树脂，主要分布在我国云南及东南亚国家。树皮被割破，便会流出殷红的汁液，像人体的鲜血，主要成份为龙血素B，微有清香，味淡微涩。具有活血散瘀，定痛止血，敛疮生肌的功效。适用于跌打损伤，瘀血作痛，外伤出血等症。国内学者的大量研究结果表明，中国产龙血竭的化学成分与来源于西亚和北非的龙舌兰科龙血树属植物树脂血竭(dragon’s blood)的化学成分有显著的相似性。二者均含有查耳酮类、多聚查耳酮类、黄烷类、高异黄烷类、色原酮类、黄酮类、简单酚类、甾体皂甙类、三萜类、脂肪醇及其酯类等类型的化学成分。目前，龙血竭的提取多采用乙醇进行提取，所得提取物主要用于抑制静脉血栓形成、抑制局灶性脑缺血、治疗缺血性脑水肿等，如申请号为02129688.X的中国发明专利“一种龙血竭总黄酮制备工艺及其新用途”。该制备工艺为将龙血竭药材粉碎成粗粉，加乙酸乙酯回流提取，滤过，回收乙酸乙酯并浓缩至干；CN201310428409.9龙血竭提取物的制备方法与用途及其化妆水，包括以下步骤的制备方法制备的：取龙血竭原药材，加入3～9倍重量的有机溶剂回流提取，浓缩，干燥，得龙血竭提取物。而CN86108273血竭的制取方法，提供了一种新的碱提方法，是将原料加入提取罐中，用一定量的稀碱溶液常温或加热浸提一定时间，滤出碱提取液，加酸中和过滤，沉淀加乙醇溶液溶解过滤或离心分离。将溶解液浓缩并回收乙醇，浓缩液干燥即得产品。其特点是节约乙酸乙酯和乙醇等有机溶剂，。但是上述的碱提工艺制备的龙血竭与醇提工艺制备的龙血竭相比在外观和内在质量上均存在较大的差距，如要替代醇提工艺尚有待进一步改进。
发明内容
为了解决上述问题，本发明公开了一种龙血竭的提取方法及其应用。
本发明的技术方案如下：
一种龙血竭的提取方法，包括以下步骤：
1)前处理：割破龙血树的树皮，流出树脂，将树脂冷却成块，自然干燥为龙血竭原料药材，将上述原料药材投入粉碎机搅拌30-60min，得原料A；
2)浸出除杂：用去离子水浸泡2-4h，辅以超声波除杂，过滤，将滤饼再加入浸出液中浸出，加热至40-50℃，浸泡1-2h，脱游离糖和脂；随后纱布过滤取滤渣，用去离子水洗净,烘干，研磨后过100-200目筛，得到原料B；
3)超临界萃取：用萃取溶剂，进行原料B的超临界萃取，萃取压力为35～45MPa，温度为55-65℃，萃取时间为30—40min，萃取溶剂流量为10-20kg/h；萃取流出物的解析过程为三级，第一级解析压力15-20MPa，解析温度为50～60℃，第二级解析压力6-12MPa，解析温度为40～50℃，第三级解析压力2-3.5MPa，解析温度为30-40℃弃去提取部分，收集萃取残余物，即为原料C；
4)碱提：将得到的原料C与3-6wt％NaOH溶液按质量比1:10-20混合后，投入反应釜中，在压力5-10Mpa,40-60℃下浸提1-3h，提取2～4次，合并提取液，为原料D；
5)旋转蒸发：将原料D放入旋转蒸发装置，加热旋转蒸发至固形物含量为30-60wt％，得到原料E；
6)真空干燥：将原料E放入真空干燥箱中，低温真空干燥至含水量低于10％，得到原料F；
7)预冻：将原料F平铺，厚度为1cm以下，放入冷冻装置，以5-8℃/min的降温速度，快速降温至-30℃以下，得到原料G；
8)冷冻干燥：在原料G中加入最终含量5-10wt％冷冻干燥保护剂，均匀混合后，放入冻干机冷冻干燥，进行以下A-D冷冻干燥循环2-4次得到原料H：
A:-35～-45℃，压强1000-2000Pa，冻干30-60min；
B：-45～-55℃，压强500-1000Pa,冻干60-90min；
C：-55～-65℃，压强200-500Pa,冻干30-50min；
D：-65～-80℃，压强100-200Pa,冻干50-100min；
9)真空包装：将原料H缓慢升温至常温，得龙血竭提取物，真空包装。
本技术方案中，使用前处理和浸出除杂，可以去掉大部分的游离糖和杂质脂类，方便进行后处理，以及最后产物的纯化，并且本发明使用超临界萃取，选取合适的萃取溶剂，结合碱提法，将龙血竭中的有效成分主要是龙血素B最大程 度的保留提取出来，并降低了醇提法中有机溶剂的使用量，最后使用真空干燥程序，对龙血竭有效成分龙血素B进行干燥和保存，方便作用药物原料使用。
进一步的，上述一种龙血竭的提取方法，所述步骤2)的浸出液为wt30％的乙醇。
进一步的，上述一种龙血竭的提取方法，所述步骤2)的浸出液按重量份数计包括0.5-1份盐酸、2-4份乙醇和10份水。上述浸出液相比单纯的乙醇浸出液，获得的龙血素B的含量更多。
进一步的，上述一种龙血竭的提取方法，所述步骤3)萃取溶剂为乙酸乙酯。
进一步的，上述一种龙血竭的提取方法，所述步骤3)萃取溶剂按重量份数包括四乙二醇醚1-2份、三氯乙烯2-3份、乙酸乙酯10份。上述的萃取溶剂，相比传统的乙酸乙酯，获得的龙血素B含量更多。
进一步的，上述一种龙血竭的提取方法，所述步骤6)中，低温真空干燥的参数为40-50℃，压力小于133Pa。
进一步的，上述一种龙血竭的提取方法，所述步骤8)中，冷冻干燥保护剂为甘油。
进一步的，上述一种龙血竭的提取方法，所述步骤8)中，冷冻干燥保护剂为改性海藻糖，所述改性海藻糖经过如下步骤的改性：
I.称取海藻糖原料投入含有质量分数为1-3％氢氧化钠的溶液中超声波清洗10-20min，过滤溶液后，放入质量分数0.5-1％的冰醋酸溶液中，对上述溶液进行抽滤，然后用95％以上乙醇沉淀洗涤，干燥，获得预处理海藻糖；
II.将预处理海藻糖与质量分数5-10％醋酸溶液加入反应容器，所述海藻糖原料与所述醋酸溶液的质量体积比为1g：5-10mL；冰水浴控制反应温度在0～5℃；在搅拌的状态下加入羟化卵磷脂；滴加完毕后撤去冰水浴，在室温下持续搅拌反应2～4h；经静置、沉淀、抽滤、干燥、重结晶得到改性海藻糖；其中所述预处理海藻糖与羟化卵磷脂的质量比为1：(0.3～0.5)。
使用上述改性海藻糖，最后龙血竭的得率相比使用甘油更高。
进一步的，上述一种龙血竭的提取方法制备获得的龙血竭。
进一步的，上述龙血竭在制备治疗过敏性鼻炎的药物中的用途，所述药物为喷鼻剂，每喷中含有100-200μg所述龙血竭提取物。在实施例中，可以看到每喷 添加了100-200μg所述龙血竭的传统鼻炎喷剂，对于过敏性鼻炎的质量效果明显更好。
相比现有技术，本发明具有如下有益效果:
本发明公开了一种龙血竭的提取方法及其应用，本发明使用前处理和浸出除杂，可以去掉大部分的游离糖和杂质脂类，方便进行后处理，以及最后产物的纯化，并且本发明使用超临界萃取，选取合适的萃取溶剂，结合碱提法，将龙血竭中的有效成分主要是龙血素B最大程度的保留提取出来，并降低了醇提法中有机溶剂的使用量，最后使用真空干燥程序，对龙血竭有效成分龙血素B进行干燥和保存，方便作用药物原料使用；进一步的，本发明使用定制的浸出液和萃取溶剂相比单纯的乙醇浸出液以及乙酸乙酯萃取溶剂，获得的龙血素B的含量更多；使用定制的改性海藻糖作为保护剂，获得的龙血竭得率更高。并且本发明还公开了上述龙血竭有效成分主要是龙血素B的应用，每喷添加了100-200μg所述龙血竭的传统鼻炎喷剂，对于过敏性鼻炎的质量效果明显更好。
本发明公开的龙血竭的提取方法相比现有技术，有机溶剂的使用量少，提取条件温和，保留天然成分多，获得的提取物中杂质含量少，并且还发现本发明公布的提取方法提取获得的龙血竭提取为对于过敏性鼻炎的治疗也具有良好的效果，可以作为有效成分添加在传统的抗过敏药物中，发挥协调增效作用，并且本提取物为纯天然物质，毒副作用小。
图1为本发明所述龙血竭的提取流程图；
图2为测试例1中龙血竭提取物得率(％)的比较图；
图3为测试例1中龙血素B的含量(％)的比较图；
图4为测试例1中龙血素B的绝对量(mg)；
图5为测试例2中治疗前后的治疗效果比较图。
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其它实施例，都属于本发明保护的范围。
本发明实施例中使用的试剂或仪器未注明生产厂商者，均为可以通过市购获得的常规试剂产品。
实施例1
一种龙血竭的提取方法，包括以下步骤：
1)前处理：割破龙血树的树皮，流出树脂，将树脂冷却成块，自然干燥为龙血竭原料药材，将上述原料药材投入粉碎机搅拌30min，得原料A 100g；
2)浸出除杂：用去离子水浸泡2h，辅以超声波除杂，过滤，将滤饼再加入浸出液中浸出，加热至40℃，浸泡1h，脱游离糖和脂；随后纱布过滤取滤渣，用去离子水洗净,烘干，研磨后过100目筛，得到原料B；
3)超临界萃取：用萃取溶剂，进行原料B的超临界萃取，萃取压力为35MPa，温度为55℃，萃取时间为30min，萃取溶剂流量为10kg/h；萃取流出物的解析过程为三级，第一级解析压力15MPa，解析温度为50℃，第二级解析压力6MPa，解析温度为40℃，第三级解析压力2MPa，解析温度为30℃弃去提取部分，收集萃取残余物，即为原料C；
4)碱提：将得到的原料C与3wt％NaOH溶液按质量比1:10混合后，投入反应釜中，在压力5Mpa,40℃下浸提1h，提取2次，合并提取液，为原料D；
5)旋转蒸发：将原料D放入旋转蒸发装置，加热旋转蒸发至固形物含量为30wt％，得到原料E；
6)真空干燥：将原料E放入真空干燥箱中，低温真空干燥至含水量低于10％，得到原料F；
7)预冻：将原料F平铺，厚度为1cm以下，放入冷冻装置，以5-8℃/min的降温速度，快速降温至-30℃以下，得到原料G；
8)冷冻干燥：在原料G中加入最终含量5wt％冷冻干燥保护剂，均匀混合后，放入冻干机冷冻干燥，进行以下A-D冷冻干燥循环2次得到原料H：
A:-35～-45℃，压强1000Pa，冻干30min；
B：-45～-55℃，压强500Pa,冻干60min；
C：-55～-65℃，压强200Pa,冻干30min；
D：-65～-80℃，压强100Pa,冻干50min；
9)真空包装：将原料H缓慢升温至常温，得龙血竭提取物，真空包装；
所述步骤2)的浸出液按重量份数计包括0.5份盐酸、2份乙醇和10份水。
所述步骤3)萃取溶剂按重量份数包括四乙二醇醚1份、三氯乙烯2份、乙酸乙酯10份。
所述步骤6)中，低温真空干燥的参数为40℃，压力小于133Pa。
所述步骤8)中，冷冻干燥保护剂为改性海藻糖，所述改性海藻糖经过如下步骤的改性：
I.称取海藻糖原料投入含有质量分数为1％氢氧化钠的溶液中超声波清洗10min，过滤溶液后，放入质量分数0.5％的冰醋酸溶液中，对上述溶液进行抽滤，然后用95％以上乙醇沉淀洗涤，干燥，获得预处理海藻糖；
II.将预处理海藻糖与质量分数5％醋酸溶液加入反应容器，所述海藻糖原料与所述醋酸溶液的质量体积比为1g：5mL；冰水浴控制反应温度在0～5℃；在搅拌的状态下加入羟化卵磷脂；滴加完毕后撤去冰水浴，在室温下持续搅拌反应2h；经静置、沉淀、抽滤、干燥、重结晶得到改性海藻糖；其中所述预处理海藻糖与羟化卵磷脂的质量比为1：0.3。
实施例2
一种龙血竭的提取方法，包括以下步骤：
1)前处理：割破龙血树的树皮，流出树脂，将树脂冷却成块，自然干燥为龙血竭原料药材，将上述原料药材投入粉碎机搅拌45min，得原料A 100g；
2)浸出除杂：用去离子水浸泡2-4h，辅以超声波除杂，过滤，将滤饼再加入浸出液中浸出，加热至45℃，浸泡1.5h，脱游离糖和脂；随后纱布过滤取滤渣，用去离子水洗净,烘干，研磨后过100-200目筛，得到原料B；
3)超临界萃取：用萃取溶剂，进行原料B的超临界萃取，萃取压力为40MPa，温度为60℃，萃取时间为35min，萃取溶剂流量为15kg/h；萃取流出物的解析过程为三级，第一级解析压力18MPa，解析温度为55℃，第二级解析压力9MPa，解析温度为45℃，第三级解析压力3MPa，解析温度为35℃弃去提取部分，收集萃取残余物，即为原料C；
4)碱提：将得到的原料C与4.5wt％NaOH溶液按质量比1:15混合后，投入反应釜中，在压力8Mpa,50℃下浸提2h，提取3次，合并提取液，为原料D；
5)旋转蒸发：将原料D放入旋转蒸发装置，加热旋转蒸发至固形物含量为 45wt％，得到原料E；
6)真空干燥：将原料E放入真空干燥箱中，低温真空干燥至含水量低于10％，得到原料F；
7)预冻：将原料F平铺，厚度为1cm以下，放入冷冻装置，以5-8℃/min的降温速度，快速降温至-30℃以下，得到原料G；
8)冷冻干燥：在原料G中加入最终含量8wt％冷冻干燥保护剂，均匀混合后，放入冻干机冷冻干燥，进行以下A-D冷冻干燥循环3得到原料H：
A:-35～-45℃，压强1500Pa，冻干45min；
B：-45～-55℃，压强750Pa,冻干75min；
C：-55～-65℃，压强350Pa,冻干40min；
D：-65～-80℃，压强150Pa,冻干75min；
9)真空包装：将原料H缓慢升温至常温，得龙血竭提取物，真空包装；
所述步骤2)的浸出液按重量份数计包括0.75份盐酸、3份乙醇和10份水。
所述步骤3)萃取溶剂按重量份数包括四乙二醇醚1.5份、三氯乙烯2.5份、乙酸乙酯10份。
所述步骤6)中，低温真空干燥的参数为45℃，压力小于133Pa。
所述步骤8)中，冷冻干燥保护剂为改性海藻糖，所述改性海藻糖经过如下步骤的改性：
I.称取海藻糖原料投入含有质量分数为2％氢氧化钠的溶液中超声波清洗15min，过滤溶液后，放入质量分数0.75％的冰醋酸溶液中，对上述溶液进行抽滤，然后用95％以上乙醇沉淀洗涤，干燥，获得预处理海藻糖；
II.将预处理海藻糖与质量分数7.5％醋酸溶液加入反应容器，所述海藻糖原料与所述醋酸溶液的质量体积比为1g：8mL；冰水浴控制反应温度在0～5℃；在搅拌的状态下加入羟化卵磷脂；滴加完毕后撤去冰水浴，在室温下持续搅拌反应3h；经静置、沉淀、抽滤、干燥、重结晶得到改性海藻糖；其中所述预处理海藻糖与羟化卵磷脂的质量比为1：0.4。
实施例3
一种龙血竭的提取方法，包括以下步骤：
1)前处理：割破龙血树的树皮，流出树脂，将树脂冷却成块，自然干燥为龙血竭原料药材，将上述原料药材投入粉碎机搅拌45min，得原料A 100g；
2)浸出除杂：用去离子水浸泡3h，辅以超声波除杂，过滤，将滤饼再加入浸出液中浸出，加热至50℃，浸泡1.5h，脱游离糖和脂；随后纱布过滤取滤渣，用去离子水洗净,烘干，研磨后过150目筛，得到原料B；
3)超临界萃取：用萃取溶剂，进行原料B的超临界萃取，萃取压力为45MPa，温度为65℃，萃取时间为40min，萃取溶剂流量为20kg/h；萃取流出物的解析过程为三级，第一级解析压力20MPa，解析温度为60℃，第二级解析压力12MPa，解析温度为50℃，第三级解析压力3.5MPa，解析温度为40℃弃去提取部分，收集萃取残余物，即为原料C；
4)碱提：将得到的原料C与6wt％NaOH溶液按质量比1:20混合后，投入反应釜中，在压力10Mpa,60℃下浸提3h，提取4次，合并提取液，为原料D；
5)旋转蒸发：将原料D放入旋转蒸发装置，加热旋转蒸发至固形物含量为60wt％，得到原料E；
6)真空干燥：将原料E放入真空干燥箱中，低温真空干燥至含水量低于10％，得到原料F；
7)预冻：将原料F平铺，厚度为1cm以下，放入冷冻装置，以5-8℃/min的降温速度，快速降温至-30℃以下，得到原料G；
8)冷冻干燥：在原料G中加入最终含量10wt％冷冻干燥保护剂，均匀混合后，放入冻干机冷冻干燥，进行以下A-D冷冻干燥循环4次得到原料H：
A:-35～-45℃，压强2000Pa，冻干60min；
B：-45～-55℃，压强1000Pa,冻干90min；
C：-55～-65℃，压强500Pa,冻干50min；
D：-65～-80℃，压强200Pa,冻干100min；
9)真空包装：将原料H缓慢升温至常温，得龙血竭提取物，真空包装；
所述步骤2)的浸出液按重量份数计包括1份盐酸、4份乙醇和10份水。
所述步骤3)萃取溶剂按重量份数包括四乙二醇醚2份、三氯乙烯3份、乙酸乙酯10份。
所述步骤6)中，低温真空干燥的参数为50℃，压力小于133Pa。
所述步骤8)中，冷冻干燥保护剂为改性海藻糖，所述改性海藻糖经过如下步骤的改性：
I.称取海藻糖原料投入含有质量分数为3％氢氧化钠的溶液中超声波清洗20min，过滤溶液后，放入质量分数1％的冰醋酸溶液中，对上述溶液进行抽滤，然后用95％以上乙醇沉淀洗涤，干燥，获得预处理海藻糖；
II.将预处理海藻糖与质量分数5-10％醋酸溶液加入反应容器，所述海藻糖原料与所述醋酸溶液的质量体积比为1g：10mL；冰水浴控制反应温度在0～5℃；在搅拌的状态下加入羟化卵磷脂；滴加完毕后撤去冰水浴，在室温下持续搅拌反应4h；经静置、沉淀、抽滤、干燥、重结晶得到改性海藻糖；其中所述预处理海藻糖与羟化卵磷脂的质量比为1：0.5。
对比例1
一种龙血竭的提取方法，步骤2)中浸出液为wt30％的乙醇，其他同实施例2。
对比例2
一种龙血竭的提取方法，所述步骤3)萃取溶剂为乙酸乙酯，其他同实施例2。
对比例3
一种龙血竭的提取方法，所述步骤8)中，冷冻干燥保护剂为甘油，其他同实施例2。
测试例1
对实施例1-3以及对比例1-3的提取获得的龙血竭提取物,比较其最后得到的龙血竭提取物的得率(冻干后最终的质量/原料量)，以及其中的龙血素B的含量和绝对量。龙血素B的含量通过HPLC检测，色谱条件如下：
色谱柱：cl8柱(5μm，4.6mm×250mm)；
流动相：1％冰醋酸溶液：乙腈(63：37)：
检测波长：26Onm；
柱温：3O℃左右；
进样体积lOμL；
运行时间20min。
结果见表1和附图2-4。
表1不同方法获得的龙血竭提取物比较
由表1的数据可知，实施例1-3制备得到的龙血竭提取物的得率均在8.2％以上，并且其中龙血素B的含量均在12.3％以上，而对比例1-3均有不同程度下降，证明本发明中的定制的浸出液和萃取溶剂相比单纯的乙醇浸出液以及乙酸乙酯萃取溶剂，获得的龙血素B的含量更多；使用定制的改性海藻糖作为保护剂，获得的龙血竭提取物得率更高。
实施例4
制备例
一种鼻喷雾剂，由龙血竭提取物和辅料制成，其中龙血竭提取物由实施例2的方法制备，辅料含有葡萄糖、微晶纤维素和羧甲基纤维素钠、苯乙醇、防腐剂苯扎氯铵、吐温80、稀盐酸和纯水(即现有的丙酸氟替卡松鼻喷雾剂中的辅料商品名称：辅舒良)；每喷含有龙血竭提取物150μg。
实施例5
一种鼻喷雾剂，即现有的丙酸氟替卡松鼻喷雾剂商品名称：辅舒良；每喷含有丙酸氟替卡松50μg。
实施例6
制备例
一种鼻喷雾剂，龙血竭提取物和丙酸氟替卡松溶于鼻喷雾剂中，其中龙血竭提取物由实施例2的方法制备，辅料含有葡萄糖、微晶纤维素和羧甲基纤维素钠、苯乙醇、防腐剂苯扎氯铵、吐温80、稀盐酸和纯水(即现有的丙酸氟替卡松鼻 喷雾剂中的辅料商品名称：辅舒良)；每喷含有龙血竭提取物150μg和酸氟替卡松50μg。
测试例2
将实施例4-6制备的鼻喷雾剂，施用于过敏性鼻炎患者，160名患者，随机分成4组，每组30人。分别施加实施例4-6的鼻炎喷剂和阴性对照(只含有辅料的喷剂)，每天早晚1喷，治疗1日后，根据表2疗效评价表进行打分，每组计算总分，得到表3的治疗效果表，以及图5。
表2疗效评价表
表3治疗效果表
| 治疗前 | 治疗后 | |
| 实施例4 | 45 | 74 |
| 实施例5 | 47 | 96 |
| 实施例6 | 43 | 126 |
| 阴性对照 | 48 | 66 |
从表3数据可知本发明制备的龙血竭提取物具有一定的治疗过敏性鼻炎的效果，但是并未达到传统西药丙酸氟替卡松的效果，单独使用丙酸氟替卡松可以使疗效达到96，但是将龙血竭提取物和西药丙酸氟替卡松联用后，能够将治疗效果提升到120以上，证明龙血竭提取物和西药丙酸氟替卡松在治疗过敏性鼻炎方面具有较好的协同增效作用。具有良好的市场前景。
上述实施例只是本发明的有限几种优选实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。
Claims (10)
- 一种龙血竭的提取方法，其特征在于，包括以下步骤：1)前处理：割破龙血树的树皮，流出树脂，将树脂冷却成块，自然干燥为龙血竭原料药材，将上述原料药材投入粉碎机搅拌30-60min，得原料A；2)浸出除杂：用去离子水浸泡2-4h，辅以超声波除杂，过滤，将滤饼再加入浸出液中浸出，加热至40-50℃，浸泡1-2h，脱游离糖和脂；随后纱布过滤取滤渣，用去离子水洗净,烘干，研磨后过100-200目筛，得到原料B；3)超临界萃取：用萃取溶剂，进行原料B的超临界萃取，萃取压力为35～45MPa，温度为55-65℃，萃取时间为30—40min，萃取溶剂流量为10-20kg/h；萃取流出物的解析过程为三级，第一级解析压力15-20MPa，解析温度为50～60℃，第二级解析压力6-12MPa，解析温度为40～50℃，第三级解析压力2-3.5MPa，解析温度为30-40℃弃去提取部分，收集萃取残余物，即为原料C；4)碱提：将得到的原料C与3-6wt％NaOH溶液按质量比1:10-20混合后，投入反应釜中，在压力5-10Mpa,40-60℃下浸提1-3h，提取2～4次，合并提取液，为原料D；5)旋转蒸发：将原料D放入旋转蒸发装置，加热旋转蒸发至固形物含量为30-60wt％，得到原料E；6)真空干燥：将原料E放入真空干燥箱中，低温真空干燥至含水量低于10％，得到原料F；7)预冻：将原料F平铺，厚度为1cm以下，放入冷冻装置，以5-8℃/min的降温速度，快速降温至-30℃以下，得到原料G；8)冷冻干燥：在原料G中加入最终含量5-10wt％冷冻干燥保护剂，均匀混合后，放入冻干机冷冻干燥，进行以下A-D冷冻干燥循环2-4次得到原料H：A:-35～-45℃，压强1000-2000Pa，冻干30-60min；B：-45～-55℃，压强500-1000Pa,冻干60-90min；C：-55～-65℃，压强200-500Pa,冻干30-50min；D：-65～-80℃，压强100-200Pa,冻干50-100min；9)真空包装：将原料H缓慢升温至常温，得龙血竭提取物，真空包装。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤2)的浸出液为wt30％的乙醇。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤2)的浸出液按重量份数计包括0.5-1份盐酸、2-4份乙醇和10份水。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤3)萃取溶剂为乙酸乙酯。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤3)萃取溶剂按重量份数包括四乙二醇醚1-2份、三氯乙烯2-3份、乙酸乙酯10份。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤6)中，低温真空干燥的参数为40-50℃，压力小于133Pa。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤8)中，冷冻干燥保护剂为甘油。
- 根据权利要求1所述的一种龙血竭的提取方法，其特征在于，所述步骤8)中，冷冻干燥保护剂为改性海藻糖，所述改性海藻糖经过如下步骤的改性：I.称取海藻糖原料投入含有质量分数为1-3％氢氧化钠的溶液中超声波清洗10-20min，过滤溶液后，放入质量分数0.5-1％的冰醋酸溶液中，对上述溶液进行抽滤，然后用95％以上乙醇沉淀洗涤，干燥，获得预处理海藻糖；II.将预处理海藻糖与质量分数5-10％醋酸溶液加入反应容器，所述海藻糖原料与所述醋酸溶液的质量体积比为1g：5-10mL；冰水浴控制反应温度在0～5℃；在搅拌的状态下加入羟化卵磷脂；滴加完毕后撤去冰水浴，在室温下持续搅拌反应2～4h；经静置、沉淀、抽滤、干燥、重结晶得到改性海藻糖；其中所述预处理海藻糖与羟化卵磷脂的质量比为1：(0.3～0.5)。
- 如权利要求1-8任一项所述的龙血竭的提取方法制备获得的龙血竭提取物。
- 如权利要求9所述的龙血竭在制备治疗过敏性鼻炎的药物中的用途，其特征在于，所述药物为喷鼻剂，每喷中含有100-200μg所述龙血竭提取物。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5063244A (en) * | 1990-07-30 | 1991-11-05 | Development Center For Biotechnology | Process for the isolation of antifungal agents (5-methoxy-7-hydroxyflavan) from dragon's blood resin and its use in agriculture |
| CN1739707A (zh) * | 2005-07-28 | 2006-03-01 | 上海大学 | 具有α－糖苷酶抑制活性的龙血竭提取物及其制剂的工艺方法和用途 |
| CN1857570A (zh) * | 2006-03-30 | 2006-11-08 | 上海大学 | 中药龙血竭黄酮类提取物的制备工艺方法 |
| CN101411833A (zh) * | 2008-12-12 | 2009-04-22 | 北京理工亘元医药技术开发中心有限公司 | 一种龙血竭提取物及其制备方法和用途 |
| CN109419981A (zh) * | 2017-08-28 | 2019-03-05 | 南京泽朗医药技术有限公司 | 一种龙血竭总黄酮的制备方法 |
| CN111686056A (zh) * | 2020-06-13 | 2020-09-22 | 云南民族大学 | 一种含天然龙血竭提取物的润唇膏制作方法 |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5063244A (en) * | 1990-07-30 | 1991-11-05 | Development Center For Biotechnology | Process for the isolation of antifungal agents (5-methoxy-7-hydroxyflavan) from dragon's blood resin and its use in agriculture |
| CN1739707A (zh) * | 2005-07-28 | 2006-03-01 | 上海大学 | 具有α－糖苷酶抑制活性的龙血竭提取物及其制剂的工艺方法和用途 |
| CN1857570A (zh) * | 2006-03-30 | 2006-11-08 | 上海大学 | 中药龙血竭黄酮类提取物的制备工艺方法 |
| CN101411833A (zh) * | 2008-12-12 | 2009-04-22 | 北京理工亘元医药技术开发中心有限公司 | 一种龙血竭提取物及其制备方法和用途 |
| CN109419981A (zh) * | 2017-08-28 | 2019-03-05 | 南京泽朗医药技术有限公司 | 一种龙血竭总黄酮的制备方法 |
| CN111686056A (zh) * | 2020-06-13 | 2020-09-22 | 云南民族大学 | 一种含天然龙血竭提取物的润唇膏制作方法 |
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