CN1568960A - High purity chlorogenic acid prescription - Google Patents
High purity chlorogenic acid prescription Download PDFInfo
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- CN1568960A CN1568960A CN 200410022438 CN200410022438A CN1568960A CN 1568960 A CN1568960 A CN 1568960A CN 200410022438 CN200410022438 CN 200410022438 CN 200410022438 A CN200410022438 A CN 200410022438A CN 1568960 A CN1568960 A CN 1568960A
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Abstract
The invention relates to the medicament by using high purity chlorogenic acid as raw material, wherein the chlorogenic acid content is 95%-105%, the medicament can be prepared into different dosage forms including injection, germ-free powder injection, tablet, capsule, oral liquid, eye drops, ointment, and various controlled release formulation.
Description
Technical field the present invention relates to a kind of pharmaceutical preparation.The various preparations of high concentration chlorogenic acid particularly.
Background technology chlorogenic acid (3-caffeoylquinic acids), its chemical constitution is as follows:
Being the class phenylpropyl alcohol chlorins compound that plant is produced through cinnamic acid approach (cinnamic acid pathway) in the aerobic respiration process, is the effective ingredient of many Chinese crude drugs (as Flos Lonicerae, coffee bean, the Cortex Eucommiae, Herba Artemisiae Scopariae, Boehmeria etc.).
Chlorogenic acid has significant pharmacologically active, and is all effective in cure to digestive system, blood system and reproductive system.Have antibacterial action more widely, and antiviral, antimutagen and antineoplastic action are arranged.Improve central nervous excitation in addition in addition, strengthen small intestinal peristalsis, promote bile secretion, function of gallbladder promoting, and stop blooding, increase leukocyte effect, shortening blood clotting and bleeding time and antioxidant activity.The choleretic effect of Herba Artemisiae Scopariae, hemostasis of Boehmeria and function of increasing leukocyte etc. all have substantial connection with chlorogenic acid.The hydrolyzate caffeic acid of chlorogenic acid also has the effect of function of gallbladder promoting, leukocyte increasing; It is to various acute bacterial infection diseases and by the leukopenia due to radiotherapy, the chemotherapy significant curative effect is arranged.(Gao Jinming etc., chlorogenic acid distribution, extraction and bioactivity research summary, Xibei Forest College's newspaper 1999,14 (2) 73~82)
Because the chlorogenic acid determined curative effect, now, chlorogenic acid is not only the quality control index of crude drug, and is the quality control index of some patent medicine and preparation.Many Chinese patent medicines as YINHUANG KOUFUYE, Flos Lonicerae injection etc., all are to make feedstock production with the Flos Lonicerae extract that is rich in chlorogenic acid.In addition, chlorogenic acid still is important chemical reagent, costs an arm and a leg.Some achievements in research have been reported the many stem-winding potential clinical value of chlorogenic acid recently, mainly comprise: acquired immune deficiency syndrome (AIDS), cancer and treatment of diabetes.(Chen Shaozhou etc., the progress of chlorogenic acid and application prospect in the certain herbaceous plants with big flowers cypress, food and fermentation industries 28 (11) 51~54)
1.McDougall point out in the research report that one piece of relevant HIV (human immunodeficiency virus) (HIV) is duplicated in the histiocyte culture fluid: chlorogenic acid and some coffeic acyl quininic acid derivatives can suppress HIV (human immunodeficiency virus) and duplicate in host cell, and it is need centesimal concentration, and different with existing anti-hiv drug and may become a kind of new treating AIDS medicine with the binding site of virus.(Kwon?H?C?et?al.Chem.Pharm.Bull.,2000,48(11):1796-8)
2.1997 year German Hemmerle discovers that chlorogenic acid can effectively suppress the activity of the 6-phosphoglucokinase in the hepatocyte and reduce the catabolism of liver glycogen, thereby blood sugar lowering concentration.This is found to be the diabetes remedy that people provide a kind of non-dependence insulin.(Hemmerle?H?etal.J.of?Medicinal?Chemistry,1997,40(2):137-45)
3. many animal experiments discover that chlorogenic acid can effectively suppress carcinogen chemical reaction in vivo, and play an important role in the oncogenic potential of regulating toxic chemical.These researchs have using value for the chemical prevention and the treatment of cancer.Discovered in 1997 and take the generation that chlorogenic acid could prevent and reduce the mice rectal cancer.(Tanaka?T?et?al.Carcinogenesis,1993,14.1321-5)
4. antioxidant and free radical effect.Grace studies show that chlorogenic acid can prevent a kind of nitrous acid category material--the Oxidation of Peroxynitrite (peroxynitrite, a kind of main deleterious oxidant that produces in the human body can damage many mechanism of biomolecule) is to the infringement of DNA.Chlorogenic acid also can stop or repair the infringement to molecule in the body that is caused by free radical.(Matsushig?et?al.Wakan?IyakugakuZashi,1996,13(13):217-28)
Chlorogenic acid is as a kind of effective Chinese medicinal ingredients, it is the qualitative or quantitative target of kind of Chinese patent medicine surplus in the of about 170, but in these in the patent medicine, chlorogenic acid all is to be used as medicine with blending ingredients, rather than be extracted into high-purity chlorogenic acid and be used as medicine, the a drug amount is equivalent to about 1 milligram of high-purity chlorogenic acid, the preparation that is prepared into, can not give full play to the pharmacological effect of chlorogenic acid on the one hand, their invalid elements are many on the other hand, the formulation of quality index and check be difficulty all, be difficult to obtain the approval of developed country, so the Chinese medicine westernization is a kind of main means of the modernization of Chinese medicine.We find directly to extract content and carry out pharmaceutical preparation research and apply to clinical not appearing in the newspapers greater than 95% chlorogenic acid when extracting high-purity chlorogenic acid and carry out research such as pharmacy, pharmacology.
Summary of the invention purpose of the present invention provides a kind of high concentration chlorogenic acid that adopts just in order to overcome above-mentioned weak point of the prior art be the medicine that feedstock production becomes pharmaceutically to can be applicable to clinical various dosage forms.
The present invention adopt content at chlorogenic acid 1mg~3g of 95%-105% as raw material, prepare ejection preparation and oral formulations, be respectively:
1. make the injection liquid in use for intravenous injection of the sodium chloride-containing 0.9% of 0.5~1000ml with chlorogenic acid 1mg~3g;
2. use the sterile powder injection of the sodium chloride-containing of chlorogenic acid 1mg-3g preparation;
3. the aseptic freeze-dried injectable powder of the sodium chloride-containing of making through lyophilizing with chlorogenic acid 1mg-3g;
4. use the glucose injection of chlorogenic acid 1mg-3g preparation;
5. use the aseptic freeze-dried injectable powder of the glucose injection of chlorogenic acid 1mg-3g preparation;
6. with chlorogenic acid interactional saccharide injection and sterile powder injection do not take place with chlorogenic acid 1mg-3g preparation other sugar except that glucose as sorbitol, fructose, xylitol etc.;
7. with every tablet of tablet that contains 1mg-3g of chlorogenic acid preparation;
8. with every capsule that contains 1mg-3g of chlorogenic acid preparation;
9. with every various sustained-release preparations that contain 1mg-3g of chlorogenic acid preparation;
10. with every eye drop that contains 1mg-3g of chlorogenic acid preparation;
11. every ointment that contains 1mg-3g with the chlorogenic acid preparation;
Every oral formulations that contains 1mg-3g of 12 usefulness chlorogenic acids preparation;
Other component of above-mentioned ejection preparation, oral formulations and other preparation is pressed the conventional preparation of said preparation.
The present invention compared with prior art has following advantage:
Can give full play to the pharmacological effect of chlorogenic acid on the one hand, the purity of chlorogenic acid and content height on the other hand, the formulation of quality index and check operation is easily studied by modern chemistry pharmaceutical research program fully, and all research datas and result can access the approval of developed country.
Specific embodiment the present invention is described in further detail below with reference to embodiment:
The injection liquid in use for intravenous injection and the eye drop of embodiment 1. preparation sodium chloride 0.9%:
Prescription one:
The chlorogenic acid 1g of content 105%
Citric acid 1.0g
Sodium citrate 0.5g
Sodium chloride 18g
Water for injection 2000ml
Make 1000 of the injections of 2ml altogether by the routine operation of injection,
Every contains 1 milligram of chlorogenic acid
Prescription two:
The chlorogenic acid 1500g of content 102%
Sodium chloride 180g
Water for injection 20000ml
Make 1000 of the injections of 20ml altogether by the routine operation of injection, every
Prop up and contain chlorogenic acid 1.5 grams
Prescription three:
The chlorogenic acid 3000g of content 99.5%
Sodium chloride 2250g
Water for injection 2000,000ml
Make 1000 bottles of the injections of 1000ml altogether by the routine operation of injection,
Every bottle contains chlorogenic acid 3 grams
Prevent the stabilizing agent of chlorogenic acid hydrolysis: as cyclodextrin clathrate, surfactant (anion surfactant, cationic surfactant, zwitterionic surfactant, non-ionic surface active agent)
Antioxidant: sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, cysteine.
The available pH value regulator of physiology: citric acid, fumaric acid, glutamic acid, L-aspartic acid, lactic acid, lactobionic acid, galacturonic acid, glucuronic acid, ascorbic acid, hydrochloric acid, acetic acid.
The sterile powder injection of embodiment 2 sodium chloride-containing
Prescription one:
The chlorogenic acid aseptic powder 1g of content 100%
Sodium chloride aseptic powder 18g
Make 1000 of 2ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain 1 milligram of chlorogenic acid
Prescription two:
The chlorogenic acid aseptic powder 1500g of content 98.5%
Sodium chloride aseptic powder 180g
Make 1000 of 20ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain chlorogenic acid 1.2 grams
Prescription three:
The chlorogenic acid aseptic powder 3000g of content 98.5%
Make 1000 of 5ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain chlorogenic acid 3 grams
The aseptic freeze-dried injectable powder of embodiment 3 sodium chloride
Embodiment 1 each formulation product is made the aseptic freeze-dried injectable powder of chlorogenic acid sodium chloride through the freeze-drier lyophilization.
5% glucose injection liquid in use for intravenous injection and eye drop of embodiment 4 chlorogenic acids:
Prescription one:
The chlorogenic acid 1g of content 99.5%
Citric acid 1.0g
Sodium citrate 0.5g
Glucose 100g
Water for injection 2000ml
Make 1000 of the injections of 2ml altogether by the routine operation of injection,
Every contains 1 milligram of chlorogenic acid
Prescription two:
The chlorogenic acid 1500g of content 99.5%
Glucose 1000g
Water for injection 20000ml
Make 1000 of the injections of 20ml altogether by the routine operation of injection, every
Prop up and contain chlorogenic acid 1.5 grams
Prescription three:
The chlorogenic acid 3000g of content 98.5%
Glucose 10,000g
Water for injection 2000,000ml
Make 1000 bottles of the injections of 1000ml altogether by the routine operation of injection,
Every bottle contains chlorogenic acid 3 grams
Prevent the stabilizing agent of chlorogenic acid hydrolysis: as cyclodextrin clathrate, surfactant (anion surfactant, cationic surfactant, zwitterionic surfactant, non-ionic surface active agent)
Antioxidant: sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, cysteine.
The available pH value regulator of physiology: citric acid, fumaric acid, glutamic acid, L-aspartic acid, lactic acid, lactobionic acid, galacturonic acid, glucuronic acid, ascorbic acid, hydrochloric acid, acetic acid.
Embodiment 5 contains the sterile powder injection of glucose
Prescription one:
The chlorogenic acid aseptic powder 1g of content 105%
Glucose aseptic powder 100g
Make 1000 of 2ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain 1 milligram of chlorogenic acid
Prescription two:
The chlorogenic acid aseptic powder 1500g of content 99.5%
Glucose aseptic powder 1000g
Make 1000 of 20ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain chlorogenic acid 1.2 grams
Prescription three:
The chlorogenic acid aseptic powder 3000g of content 99.5%
Make 1000 of 5ml injectable powder altogether by the routine operation of sterile powder injection, every
Prop up and contain chlorogenic acid 3 grams
The aseptic freeze-dried injectable powder of embodiment 6 glucoses
Embodiment 4 each formulation product are made the aseptic freeze-dried injectable powder of chlorogenic acid sodium chloride through the freeze-drier lyophilization.
Embodiment 7 chlorogenic acid tablets:
Prescription one:
Content is 95.0% chlorogenic acid 1.00g
Starch 184.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 200.00g
Make 1000 altogether, every contains chlorogenic acid 1mg.
Prescription two:
Content is 95.0% chlorogenic acid 100.00g
Starch 85.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 200.00g
Make 1000 altogether, every contains chlorogenic acid 100mg.
Prescription three:
Content is 95.0% chlorogenic acid 300.00g
Starch 85.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 400.00g
Make 1000 altogether, every contains chlorogenic acid 300mg.
Filler: as starch, dextrin, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, calcium bicarbonate.
Adhesive: as hypromellose, polyvidone, starch slurry, dextrin slurry, syrup, rubber cement, sodium alginate, Polyethylene Glycol, Resina persicae, arabic gum.
Disintegrating agent: as cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, hydroxypropyl starch, low-substituted hydroxypropyl cellulose citric acid, tartaric acid, anhydride, sodium bicarbonate, sodium carbonate.
Embodiment 8 chlorogenic acid capsules:
Prescription one:
Content is 95.0% chlorogenic acid 1.00g
Starch 186.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 200.00g
Make 1000 capsules altogether, every capsules contains chlorogenic acid 1mg.
Prescription two:
Content is 95.0% chlorogenic acid 100.00g
Starch 85.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 200.00g
Make 1000 capsules altogether, every capsules contains chlorogenic acid 100mg.
Prescription three:
Content is 98.0% chlorogenic acid 300.00g
Starch 85.00g
Polyvinylpyrrolidone 5.00g
Magnesium stearate (120 order) 10.00g
Amount to 400.00g
Make 1000 capsules altogether, every capsules contains chlorogenic acid 300mg.
Filler: as starch, dextrin, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, calcium bicarbonate.
Adhesive: as hypromellose, polyvidone, starch slurry, dextrin slurry, syrup, rubber cement, sodium alginate, Polyethylene Glycol, Resina persicae, arabic gum.
Embodiment 9
Soft capsule:
Prescription:
The chlorogenic acid of content 95.0%
Substrate: as vegetable oil (salad oil, Oleum Ricini, oil with hydrogenated soybean), Polyethylene Glycol (300,400,6000).
Antioxidant: sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, cysteine, butylated hydroxyarisol, two fourth cresols, vitamin E.
Embodiment 10
Oral sustained-release preparation:
Prescription:
The chlorogenic acid of content 98.0%
Blocker: as Cera Flava, Brazil wax, hydrogenated vegetable oil, stearyl alcohol, glyceryl monostearate, the cellulose acetate phthalate ester, acrylic resin L, the S type, the hypromellose phthalate ester, Hydroxypropyl Methyl Cellulose Phthalate, methylcellulose, sodium carboxymethyl cellulose, hypromellose, polyvidone, carbopol, sodium alginate, chitosan, ethyl cellulose, polymethacrylates, non-toxic polyvinyl chloride, polyethylene, ethylene-vinyl acetate copolymer, silicone rubber.
Thickening agent: as gelatin, polyvidone, sodium carboxymethyl cellulose, polyvinyl alcohol, dextran.
Embodiment 11
Ointment:
Prescription:
The chlorogenic acid of content 98.0%
Substrate: as vaseline, paraffin, lanoline, Cera Flava, dimethicone, hydrogenated vegetable oil, stearic acid, Oleum Ricini, triethanolamine, hexadecanol, octadecanol, Lauryil Sodium, sodium dodecyl, tristerin, glycerol, gelatin solution paraffin body, carbopol, sodium alginate, methylcellulose, sodium carboxymethyl cellulose, Polyethylene Glycol.
Claims (1)
1. high-purity chlorogenic acid preparation is characterized in that: adopt content at chlorogenic acid 1mg~3g of 95%-105% as raw material, prepare ejection preparation and oral formulations, be respectively
1.1 make the injection liquid in use for intravenous injection of the sodium chloride-containing 0.9% of 0.5~1000ml with chlorogenic acid 1mg~3g;
1.2 sterile powder injection with the sodium chloride-containing of chlorogenic acid 1mg-3g preparation;
1.3 the aseptic freeze-dried injectable powder of the sodium chloride-containing of making through lyophilizing with chlorogenic acid 1mg-3g;
1.4 glucose injection with chlorogenic acid 1mg-3g preparation;
1.5 aseptic freeze-dried injectable powder with the glucose injection of chlorogenic acid 1mg-3g preparation;
1.6 with chlorogenic acid interactional saccharide injection and sterile powder injection do not take place with chlorogenic acid 1mg-3g preparation other sugar except that glucose as sorbitol, fructose, xylitol etc.;
1.7 every tablet of tablet that contains 1mg-3g with the chlorogenic acid preparation;
1.8 every capsule that contains 1mg-3g with the chlorogenic acid preparation;
1.9 every various sustained-release preparations that contain 1mg-3g with the chlorogenic acid preparation;
1.10 every eye drop that contains 1mg-3g with the chlorogenic acid preparation;
1.11 every ointment that contains 1mg-3g with the chlorogenic acid preparation;
1.12 every oral formulations that contains 1mg-3g with the chlorogenic acid preparation;
Other component of above-mentioned ejection preparation, oral formulations and other preparation is pressed the conventional preparation of said preparation.
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CN 200410022438 CN1568960A (en) | 2004-05-08 | 2004-05-08 | High purity chlorogenic acid prescription |
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CN 200410022438 CN1568960A (en) | 2004-05-08 | 2004-05-08 | High purity chlorogenic acid prescription |
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Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2007009392A1 (en) * | 2005-07-22 | 2007-01-25 | Jie Zhang | The use of chlorogenic acid in the manufacturing medicaments for treating and/or preventing hepatic injury |
WO2007009393A1 (en) * | 2005-07-22 | 2007-01-25 | Jie Zhang | The use of chlorogenic acid in the manufacture of medicaments for increasing the effect of bone marrow cells |
CN101147732B (en) * | 2006-09-19 | 2011-02-02 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine for preventing and treating nasopharyngeal cancer |
CN101695485B (en) * | 2005-07-22 | 2011-07-13 | 四川九章生物化工科技发展有限公司 | Use of chlorogenic acid in preparing medicament for treating thrombocytopenia and anemia |
CN101695486B (en) * | 2005-07-22 | 2011-09-07 | 四川九章生物化工科技发展有限公司 | Use of chlorogenic acid in preparing medicament for treating marrow fibrillation |
CN103446064A (en) * | 2013-08-21 | 2013-12-18 | 四川九章生物化工科技发展有限公司 | Chlorogenic acid powder-injection and preparation method thereof |
WO2015024217A1 (en) * | 2013-08-21 | 2015-02-26 | 四川九章生物科技有限公司 | Chlorogenic acid powder-injection and preparation method thereof |
WO2016045530A1 (en) * | 2014-09-22 | 2016-03-31 | 四川九章生物科技有限公司 | Chlorogenic acid lyophilised powder for injection having high resolubility and high stability |
JP2017537092A (en) * | 2014-11-24 | 2017-12-14 | スーチョアン チウチャン バイオロジカル サイエンス アンド テクノロジー カンパニー リミテッド | Formulation containing chlorogenic acid crystal form and use thereof |
CN107879937A (en) * | 2017-10-24 | 2018-04-06 | 四川九章生物科技有限公司 | A kind of new crystal of chlorogenic acid and preparation method thereof |
CN110438198A (en) * | 2019-09-05 | 2019-11-12 | 湖南农业大学 | The ramee variety and organ screening technique of antibiotic are prepared based on grass meal extract |
CN114404599A (en) * | 2022-01-11 | 2022-04-29 | 刘振宇 | Pure natural product composition capable of inhibiting L, D-transpeptidase and preparation method thereof |
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2004
- 2004-05-08 CN CN 200410022438 patent/CN1568960A/en active Pending
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007009392A1 (en) * | 2005-07-22 | 2007-01-25 | Jie Zhang | The use of chlorogenic acid in the manufacturing medicaments for treating and/or preventing hepatic injury |
WO2007009393A1 (en) * | 2005-07-22 | 2007-01-25 | Jie Zhang | The use of chlorogenic acid in the manufacture of medicaments for increasing the effect of bone marrow cells |
CN101212963B (en) * | 2005-07-22 | 2010-08-25 | 四川九章生物化工科技发展有限公司 | The use of chlorogenic acid in the manufacture of medicaments for increasing the effect of bone marrow cells |
CN101695485B (en) * | 2005-07-22 | 2011-07-13 | 四川九章生物化工科技发展有限公司 | Use of chlorogenic acid in preparing medicament for treating thrombocytopenia and anemia |
CN101695486B (en) * | 2005-07-22 | 2011-09-07 | 四川九章生物化工科技发展有限公司 | Use of chlorogenic acid in preparing medicament for treating marrow fibrillation |
CN101147732B (en) * | 2006-09-19 | 2011-02-02 | 四川九章生物化工科技发展有限公司 | Application of chlorogenic acid in preparing medicine for preventing and treating nasopharyngeal cancer |
CN103446064B (en) * | 2013-08-21 | 2015-04-15 | 四川九章生物科技有限公司 | Chlorogenic acid powder-injection and preparation method thereof |
WO2015024217A1 (en) * | 2013-08-21 | 2015-02-26 | 四川九章生物科技有限公司 | Chlorogenic acid powder-injection and preparation method thereof |
CN103446064A (en) * | 2013-08-21 | 2013-12-18 | 四川九章生物化工科技发展有限公司 | Chlorogenic acid powder-injection and preparation method thereof |
EP3040067A4 (en) * | 2013-08-21 | 2017-03-22 | Sichuan Jiuzhang Biological Science And Technology Co., Ltd | Chlorogenic acid powder-injection and preparation method thereof |
US9918956B2 (en) | 2013-08-21 | 2018-03-20 | Sichuan Jiuzhang Biological Science And Technology Co., Ltd | Chlorogenic acid powder-injection and preparation method thereof |
WO2016045530A1 (en) * | 2014-09-22 | 2016-03-31 | 四川九章生物科技有限公司 | Chlorogenic acid lyophilised powder for injection having high resolubility and high stability |
JP2017537092A (en) * | 2014-11-24 | 2017-12-14 | スーチョアン チウチャン バイオロジカル サイエンス アンド テクノロジー カンパニー リミテッド | Formulation containing chlorogenic acid crystal form and use thereof |
CN107879937A (en) * | 2017-10-24 | 2018-04-06 | 四川九章生物科技有限公司 | A kind of new crystal of chlorogenic acid and preparation method thereof |
CN110438198A (en) * | 2019-09-05 | 2019-11-12 | 湖南农业大学 | The ramee variety and organ screening technique of antibiotic are prepared based on grass meal extract |
CN114404599A (en) * | 2022-01-11 | 2022-04-29 | 刘振宇 | Pure natural product composition capable of inhibiting L, D-transpeptidase and preparation method thereof |
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