CN1339298A - Compound traditional medicine with piperine for increasing biological utilization of paeoniflorin and its preparing method - Google Patents
Compound traditional medicine with piperine for increasing biological utilization of paeoniflorin and its preparing method Download PDFInfo
- Publication number
- CN1339298A CN1339298A CN 01128926 CN01128926A CN1339298A CN 1339298 A CN1339298 A CN 1339298A CN 01128926 CN01128926 CN 01128926 CN 01128926 A CN01128926 A CN 01128926A CN 1339298 A CN1339298 A CN 1339298A
- Authority
- CN
- China
- Prior art keywords
- paeoniflorin
- piperine
- herbal mixture
- extract
- weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
In oral compound Chinese medicine preparation, piperine can improve the absorption of paeoniflorin in gastrointestinal tract, increase the concentration of paeoniflorin in blood and raise the biological utilization of paeoniflorin. One typical compound Chinese medicine is paeoniae licorice decoction comprising Radix Paeoniae Alba, licorice and pepper for treating women's lower abdomen pain caused by vital energy stagnation and blood stasis. The preparation process of the present invention ensures the control of the content of different effective components in the medicine preparation.
Description
Technical field:
The present invention relates to increase the herbal mixture and the preparation method of paeoniflorin bioavailability with piperine
Background technology:
The multiple disease of gynecological, for example dysmenorrhea, urgent chronic pelvic inflammatory disease, hysteromyoma and endometriosis etc. all exist few abdomen pain and inflammation in various degree.
Theory of Chinese medical science thinks that few abdomen pain is relevant with physiological environment with organic factor, and the dialectical qi stagnation blood stasis that mostly is is a little less than the taste element.And few abdomen be footpath of Liver Channel, gas desire row and liver not should, stroke its gas and pain is living.
Treatise on Febrile Diseases ancient prescription peony and licorice decoction is the good recipe of the few abdomen pain of treatment.Monarch drug Radix Paeoniae Alba acid receipts hardship is rushed down in the side, and the moon cold in nature is gentle, holds back ying-qi eliminating pathogen in the liver wood.In the TCM Gynecology field, the Chinese medicine compound of treatment dysmenorrhea, pelvic inflammatory disease, hysteromyoma and endometriosis all contains the Radix Paeoniae Alba basically and (sees Si Tuyi, Yang Jialin chief editor for details, gynecological's disease that calls for specialized treatment tcm clinical practice diagnosis and treatment, the People's Health Publisher, October in 2000 the 1st edition ISBN7-117-03827-6/R3828).
The effective ingredient paeoniflorin of monarch drug Radix Paeoniae has tangible spasmolytic, relaxing smooth muscle, antiinflammatory, analgesia and sedation in the modern medicine study discovery side.And ministerial drug Radix Glycyrrhizae in the side, the sweet slow gentle and contrary gas spleen reinforcing soil of property.Effective ingredient licoflavone of Radix Glycyrrhizae and glycyrrhizic acid also are smooth muscle contraction inhibitor and 17-hydroxy-11-dehydrocorticosterone sample antiinflammatory, no matter be single with or share, can both suppress uterine contraction and inflammatory exudation, two medicines have share synergism, and (king bathes chief editors such as life, Deng Wenlong, herbal pharmacology and application, second edition, People's Health Publisher, pp346-356; 248-260,1998, ISBN 7-117-03057-7/R3058).Above-mentioned traditional Chinese medical science doctor trained in Western medicine theoretical study results is the pharmacological basis of the few abdomen pain of peony and licorice decoction treatment gynecological.
Tcm theory thinks that the Radix Paeoniae consumption as monarch drug in the peony and licorice decoction compound recipe is big, be because few abdomen pain-suffered patient has a little less than the taste element more, and monarch drug is cold in nature, so poor appetite, absorption are not good.In the Chinese traditional treatment field, the traditional method that remedies certain flavor Chinese medicine gastrointestinal absorption difference is to strengthen the consumption of this flavor Chinese medicine when prescription.Therefore dosage every day of treatise on Febrile Diseases ancient prescription peony and licorice decoction is that four liang of Radix Paeoniaes add four liang in Radix Glycyrrhizae (ancient times one or two is roughly equal to the 31-32 gram), in later age and the modern Chinese medicine prescription, reuses Radix Paeoniae and reaches gram every days 150, can obtain obvious curative effects.(see for details Si Tuyi, Yang Jialin chief editor, gynecological's disease that calls for specialized treatment tcm clinical practice diagnosis and treatment, the People's Health Publisher, October in 2000 the 1st edition ISBN7-117-03827-6/R3828).Gently then obviously influence the curative effect of peony and licorice decoction with Radix Paeoniae.
Modern medicine and pharmacology discovers that the gastrointestinal of Radix Paeoniae its main effective ingredient paeoniflorin when orally using absorbs very poor.Behind the rat oral gavage 550mg/kg paeoniflorin, the accumulation excretion of fecaluria accounts for 10.6% and 1.08% of dosage respectively after 24 hours.Behind the quiet notes 55mg/kg paeoniflorin, bile accumulative total excretion accounts for 8.64% in 7 hours.After rabbit was irritated the stomach paeoniflorin, bioavailability was 7.24 ± 4.15% in vivo, and the highest blood drug level time (Tmax) is 77.4 minutes, and the highest blood drug level (Cmax) is 21.6mg/L.Behind the Canis familiaris L. intravenous injection 11.25mm/kg paeoniflorin, paeoniflorin appears at rapidly in the urine, and in preceding 20 minutes and 7 hours, the accumulation excretion is respectively 36.85%, 79.3% of dosage.The bile excretion accounts for 3.77% of intravenous injection amount in 7 hours.Experiment shows paeoniflorin the intestines and stomach absorption difference, in vivo mainly with original shape from renal excretion, excrement, bile excretion are minimum.Paeoniflorin blood drug level-time graph all meets two Room open models in Canis familiaris L. and rabbit body, and is widely distributed, eliminates piece, gastric infusion, low ((king bathes chief editors such as life, Deng Wenlong, herbal pharmacology and application to availability in the rabbit body, second edition, People's Health Publisher, pp352-353; 248-260,1998, ISBN7-117-03057-7/R3058).
At above-mentioned paeoniflorin gastrointestinal absorption difference and the low phenomenon of bioavailability, and the people's that cures the disease dialectical and plain body situation, Chinese medicine compound provided by the invention, on the basis of the elite that absorbs traditional outstanding ancient prescription peony and licorice decoction, further the research and development theory of Chinese medical science has added drugs for dispelling internal cold Fructus Piperis simply in compound recipe, with it is adjuvant drug, make the property of compound recipe be tending towards Wen Ping, be of value to the spleen stomach function regulating and receive, obviously increase the absorption of paeoniflorin.And, also can use the patient that cold elephant is arranged, increased the drug application scope of this compound recipe.
Piperic adding is found in dynamic test, has obviously increased the blood drug level and the bioavailability of paeoniflorin.Can improve document and summary of patent work of gastrointestinal absorption, increase blood drug level and the raising bioavailability of multiple medicine, vitamin etc. below with regard to piperic effective ingredient piperine, for gastrointestinal absorption and the bioavailability of using Fructus Piperis increase paeoniflorin among the present invention provides background and basis.
U.S. Pat-5,972,382 literature review was mentioned between sixth century of the first seven century to Christian era in Christian era, the medicine that a kind of " trikatu " arranged in India's traditional medicine, by three kinds of pungent plant Fructus Piperiss (Piper nigrumLinn.), long Fructus Piperis (Piper longum Linn.) and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.) are prepared from, and the prescription of much curing the disease all uses " trikatu " to form as the basic ingredient compound recipe.The modern medicine and pharmacology test finds that " trikatu " can improve the bioavailability of multiple Western medicine.In animal experiment and the test of human volunteer, find that the effective ingredient that " trikatu " improves the Western medicine bioavailability is a piperine.
Long-term oral anti-hypertensive drug thing Propranolol usually can not be kept the effect that obtains when beginning to take medicine.Need escalated dose just can keep curative effect.But escalated dose causes side effect to take place.Discover that piperine can increase the bioavailability of Propranolol, the blood level of Propranolol obviously increases behind the use piperine.
Piperine can also improve the blood level and the bioavailability of multiple oral western medicine, comprise rifampicin (Zutshi, U.et al.Journal of the Association of physicians ofIndia, 1984:33,223-224), phenytoin (Bano et al., Planta Medica, 1987, pp.568-569), pentobarbital (Majumdar, A.N.et al., Indian Journal of Experimental Biology, 1990:28,486-487), theophylline (Bano et al., Eur.J.Clin.Pharmacol.1991:41,615-617) and propranolol (ibid).
Indian patent No.1232/DEL/89 discloses piperine and has been used for compound recipe western medicine tuberculosis and leprosy.The test that the Western medicine compound recipe that uses rifampicin, pyrazinamide, isoniazid and piperine to form carries out human volunteer is for most drug, and piperine can increase their relative blood drug level and blood peak concentration of drug.The raising of bioavailability helps to reduce drug dose and shortens the course of treatment.
Piperine increases the mechanism of bioavailability and does not illustrate as yet.The possible mechanism of action is as follows: 1. the non-absorption that promotes medicine specifically, for example increase gastrointestinal blood supply and blood circulation, reduce the destruction that gastric acid secretion reduces some drugs, strengthen the emulsifying content in the intestinal, the interior glutamine transpeptidase of increase intestinal mucosa epithelial cell etc. is participated in initiatively and the activity of the enzyme of passive transport, 2. suppress the activity of drug disposition biotransformation enzyme, prevent medicine inactivation and eliminating.
According to document, take in the enzyme that 20mg Fructus Piperis at least just can suppress in the body medicine biotransformation to be made the medicine inactivation everyone every day.
Fructus Piperis suppresses drug disposition biotransformation enzyme, can be to use with medicaments compound, and also can be before medication or after the medication, to use.This point obtains proof in the test of using theophylline and phenytoin.Using these two kinds of medicines to give Fructus Piperis 20mg in preceding 7 days, the blood drug level of these two kinds of medicines is being improved, and obviously prolonged the time that medicine is detained in blood.Possible mechanism is that Fructus Piperis has suppressed drug disposition biotransformation enzyme.In fact, this is to improving the unique reasonable explanation of bioavailability, because Fructus Piperis separates use with medicine, can not influencing the rapid absorption of gastrointestinal tract to medicine.
Another observed phenomenon is even piperic use amount is lower than the lowest dose level that suppresses biotransformation enzyme in the body, also can increases medicine and absorb rapidly at gastrointestinal.Only need 3mg Fructus Piperis and Propranolol compound recipe, just can make the blood drug level of Propranolol increase by 2 times, but can not prolong the clearance rate of this medicine.Therefore, can think that low dose of Fructus Piperis does not suppress the clearance rate of medicine biotransformation or medicine, only increases medicine and absorbs from gastrointestinal.
60 healthy premenopausal volunteers are arranged, be divided into test group and matched group.Test group is oral Fructus Piperis 20mg/ day earlier, totally 7 days, gives theophylline 150mg or phenytoin 300mg then.The maximum plasma concentration of theophylline exceeds 1.5 times in test group than matched group, and the elimination factor of theophylline obviously slows down in test group.Phenytoin at blood drug level and blood peak concentration of drug in test group than the obvious increase of matched group.And the elimination factor of phenytoin obviously slows down in test group.
U.S. Pat-5,972,382 disclose piperine and Rhizoma Curcumae Longae, Semen Ginkgo, aconitine, vitamin B1, vitamin B2, nicotiamide, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin A, vitamin D, vitamin E, vitamin K, α carotene, lycopene, several amino acids comprises lysine, leucine, isoleucine, threonine, valine, tryptophan, the phenylalanine methionine, L-Selenomethionine and mineral comprise calcium, ferrum, zinc, vanadium, selenium, chromium, iodine, potassium, magnesium, method and result of the test that compound recipe such as copper and manganese uses.The compound recipe of Fructus Piperis and above-mentioned substance has improved them and has absorbed at gastrointestinal, has increased blood drug level, has improved the bioavailability of these nutritional labelings.
In sum, said medicine and piperine use together, can improve curative effect, mainly are that blood drug level increases because said medicine absorbs at gastrointestinal to be increased, and the half-life prolongs, and bioavailability improves.The medicine big to toxicity increases curative effect when can reduce dosage.Therefore, Fructus Piperis is a kind of drugs for dispelling internal cold and bioavailability reinforcing agent.
Summary of the invention:
Poor and piperine can improve gastrointestinal absorption, blood drug level and the bioavailability of multiple Western medicine, vitamin and mineral in view of the gastrointestinal absorption of above-mentioned paeoniflorin.The purpose of this invention is to provide a kind of herbal mixture that can increase the paeoniflorin bioavailability and preparation method thereof.The herbal mixture that this increases the paeoniflorin bioavailability is characterized in that, contains paeoniflorin and piperine in the herbal mixture.Piperine can improve the gastrointestinal absorption of paeoniflorin, makes paeoniflorin concentration increase in the blood, thereby reaches the purpose that improves the paeoniflorin bioavailability.
In this herbal mixture, the percentage by weight of paeoniflorin and piperine is respectively: paeoniflorin is 50%-99.99%, and piperine is 0.01%-50%.
The present invention is with reference to the dialectical application of treatise on Febrile Diseases ancient prescription peony and licorice decoction, and on this basis, this herbal mixture contains Radix Glycyrrhizae, and its effective ingredient is a glycyrrhizic acid.Three flavor Effective Components of Chinese Herb percentage by weights are respectively, paeoniflorin 5%-99%, and glycyrrhizic acid 5%-99%, the percentage by weight of piperine are 0.01%-30%.
The dosage form of above-mentioned Chinese traditional compound medicine according to clinical needs, can be capsule, oral liquid, granule, tablet, syrup, tincture, membrane and effervescent.
Herbal mixture of the present invention owing to contain piperine, has significantly improved the gastrointestinal absorption of paeoniflorin, has increased the blood drug level of paeoniflorin, has improved the bioavailability of paeoniflorin.Test finds, can increase the paeoniflorin bioavailability piperine dosage the mankind for every day per kilogram 0.0005mg between the 0.20mg.This dosage can be any feasible dosage.The oral dose of first-selected piperine is everyone 1.5-5mg every day.
The Radix Paeoniae Alba, Radix Glycyrrhizae and Fructus Piperis are Chinese crude drug that records of Chinese Pharmacopoeia version in 2000, three kinds of equal avirulences of Chinese medicine.Black pepper is classified as basic security draft (GRAS) by U.S. food and drug administration (FDA), as spice and flavouring agent.At the piperic consumption per capita of American Black is 359mg every day, and content of piperine is 5-9% in the black pepper, and being converted into for each person every day, the piperine consumption is 18.0-32.3mg.In the compound recipe of the present invention, piperine is as paeoniflorin bioavailability reinforcing agent, and consumption is everyone 4.5-15mg every day approximately.And the evidence piperine is at rodentine median lethal dose(LD 50) (LD
50) be equivalent to 40 of this dosage, 000-120,000 times.
Herbal mixture of the present invention obviously improves the paeoniflorin bioavailability, therefore not only can significantly strengthen the pharmacological action and the clinical efficacy of paeoniflorin, can also significantly reduce the consumption of Radix Paeoniae, and improve the thick black shortcoming of Chinese medicine.
The prescription method of herbal mixture of the present invention, can be that the Chinese medicine raw medicinal herbs of respectively distinguishing the flavor of in the compound recipe is write out a prescription by a certain percentage of the weight, also can be the weight of calculating raw medicinal herbs in the yield of the ratio of effective ingredient specific in each flavor Chinese medicine raw medicinal herbs and selected extraction process, write out a prescription after the weighing respectively then.A kind of prescription method in first-selected back.The prescription method of this Chinese medicine compound also is that the science of Chinese medicine compound formula principle is extended.Ancient times and later age prescriptions of Chinese medicine emphasize the Chinese medicine raw medicinal herbs the place of production, receive and to adopt season, the process of preparing Chinese medicine etc., prove it all is the relative fixed of each effective ingredient in the assurance Chinese traditional compound medicine, as the property of medicine of this Chinese traditional compound medicine and the prerequisite of curative effect.Through modern medicine and pharmacology its content of effective is detected, and weigh the actual content of effective ingredient in the preparation, in fact just to the fixed important method of effective ingredient in the Chinese medicine preparation with yield in the extraction process process.
Herbal mixture of the present invention, its Chinese medicine raw medicinal herbs of respectively distinguishing the flavor of is mixed into herbal mixture after can extracting respectively, also can again extract mixture be synthesized herbal mixture after the meromict extraction, and all right mixed extraction is made herbal mixture then.First-selected mixed extraction is because this is a kind of science extension of Chinese medicine compound preparation method.
Selection principle according to above-mentioned prescription and extracting method, the invention provides a kind of preparation method of herbal mixture, it is levied and is, according to the requirement of the dosage of each effective ingredient in the Chinese traditional compound medicine and the ratio between them, during mixed extraction, according to each content of effective in the raw medicinal herbs and the yield in certain technique for extracting mixed, calculate the weight of the Chinese medicine raw medicinal herbs of respectively distinguishing the flavor of, weighing respectively then mixes, and extracts.
This preparation method makes herbal mixture of the present invention, and technology advanced person is quality controllable, and the size of the active constituent content difference of the Chinese medicine raw medicinal herbs that uses no matter particularly can both guarantee the accurate content of each effective ingredient in the Chinese traditional compound medicine.
Description of drawings:
The average blood drug level of Fig. 1 represents with high pressure liquid chromatography (be called for short HPLC, back with) average peak area, point mutually during after administration in 6 hours each, the average blood drug level of test group rabbit all with the average blood drug level that is higher than matched group.
After Fig. 2 administration in 6 hours, paeoniflorin concentration in the test group rabbit accumulative total blood (each time phase HPLC average peak area and) paeoniflorin concentration (P＜0.05) in the matched group rabbit accumulative total blood.
The extraction flow chart of Fig. 3 piperine.Hainan Fructus Piperis seed is pulverized the back and is extracted 2 times with 95% ethanol room temperature, each each 2 days.The concentrating under reduced pressure extracting solution, remove ethanol after, extractum is dissolved in ether, wash 2 times with 5% aqueous sodium hydroxide washes, again through washing 2 times.Concentrating under reduced pressure ether part is scattered in extractum in the water, with ethyl acetate extraction 6 times, combined ethyl acetate part, is concentrated into driedly, and it is 80% piperine crude product that methanol crystallization promptly gets purity, and yield is 2.5%.
Flow chart is extracted in the extraction of Fig. 4 Radix Paeoniae Radix Glycyrrhizae compound recipe.The river Radix Paeoniae Alba and northeast Radix Glycyrrhizae are mixed decocting in water, little boiling 1 hour, the water extract filters to get filtrate.Residue continues to add water, handles with method.Front and back totally 4 times.The filtrate that merges 4 water extracts is gone up the absorption of macroporous resin D101 post.After impurity is removed in water flushing, use 80% alcohol flushing, the collection effluent is evaporated to driedly, obtains Radix Paeoniae Radix Glycyrrhizae compound recipe total extract, and yield is 3.9%.Content of paeoniflorin is 60% in this total extract, paeoniflorin: glycyrrhizic acid: piperine=100: 6.
The specific embodiment:
Below in conjunction with the diagram and embodiment the present invention is further detailed explanation. Example one. after using Chinese medicinal compound extract of the present invention and contrast to carry out the rabbit gavage with Chinese herbaceous peony Glycyrrhiza uralensis compound extract The mensuration of Paeoniflorin concentration in the blood 1 test objective: by the mensuration to blood concentration after the new zealand white rabbit gavage, study compound of the present invention Pipering is to the impact of the absorption of Paeoniflorin stomach and intestine and blood concentration in the Chinese medical extract. 1.2 test material: new zealand white rabbit provides hero by animal used as test center, medical science school district, Sichuan University West China The property, body weight 1.8～2.0kg. Compound Chinese medicine extract of the present invention and contrast by inventor's preparation are sweet with Chinese herbaceous peony The content of paeoniflorin of grass compound extract is 60%. Outward appearance is brown particle. The Paeoniflorin standard items are from Sichuan Province medicine inspecting institute buys, and is mixed with the methanol solution of 0.1118mg/ml. Through HPLC (high pressure liquid chromatography, after Be determined as simple spike together). 1.3 experimental condition and sample pretreatment 1.3.1 chromatographic condition mobile phase methanol-water (35: 65), fixedly phase: BDSCl8 post. Detect wavelength:
230nm, the retention t of Paeoniflorinr=11.66min. Adopt the pipering concentration in the external standard method serum. 1.3.2 the preparation rabbit ear edge venous blood sampling 1.5ml of rabbit anteserum sample, the 100 μ l anti-freezings of 0.4% liquaemin,
The centrifugal 10min of 10000r/min gets supernatant, and-15 ℃ of preservations are to be measured. 1.3.3 getting 0.5ml rabbit anteserum to be measured, the processing micro sample adding appliance essence of rabbit anteserum sample enters in the centrifuge tube,
Add 1.0ml methyl alcohol, the centrifugal 10min of 10000r/min after mixing. It is centrifugal to get supernatant 10000r/min
5min. Sample introduction 20 μ l. 1.4 test method
10 of male rabbits, animal is normal, the conventional raising, water is can't help in the test fasting evening before yesterday. With the rabbit branch
Be two groups, one group is the test group, gives Chinese medicinal compound extract gavage of the present invention, and dosage is Chinese herbaceous peony
Glucoside 500mg/kg, another group is control group. Give Chinese herbaceous peony Glycyrrhiza uralensis compound extract gavage, dosage is Chinese herbaceous peony
Medicine glucoside 500mg/kg. After the gavage 0.5 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 little
The time, got hematometry Paeoniflorin concentration in 5 hours, 6 hours. 1.5 result:
After the administration two groups of rabbits each the time phase point blood in Paeoniflorin concentration (the average peak area of HPLC) see Table 1, The difference of Paeoniflorin concentration (the average peak area of HPLC) between two groups of rabbits is seen accompanying drawing 1 in the average blood. 6 is little The time in poor between two groups of rabbits of accumulative total Paeoniflorin concentration in the blood (each time phase HPLC average peak area and) Differnce accompanying drawing 2.
Table 1: after the administration test group and control group each the time chromatographic peak area of Paeoniflorin in the blood mutually
And increase percentile relatively time test group rabbit control group rabbit (AExamination-A
Right)×100％//A
Right(hr) the average peak area (A of PaeoniflorinExamination) the average peak area (A of PaeoniflorinRight) % 0.5 5,208,093 3,478,541 49 1.0 9,244,679 6,353,795 45 1.5 6,089,456 5,185,006 17 2.0 6,294,066 5,012,983 26 3.0 6,732,372 2,975,195 126 4.0 7,230,380 2,134,814 239 5.0 6,290,451 2,109,535 198 6.0 3,350,235 2,150,820 56 1.6 statistical calculations
Give in 6 hours of rabbit of Chinese medicinal compound extract of the present invention that accumulative total Paeoniflorin concentration ratio gives in the blood Accumulative total Paeoniflorin concentration has remarkable increase (P＜0.05) in the blood of the rabbit of Chinese herbaceous peony Glycyrrhiza uralensis compound extract. 1.7 conclusion
Can observe from table 1 and accompanying drawing 1, the Paeoniflorin peak area ratio in the rabbit anteserum, 6 is little after administration The time in, in the serum of test group rabbit in the serum of Paeoniflorin peak area concentration ratio control group rabbit the Paeoniflorin peak area dense Degree is high. Can observe from accompanying drawing 2, add up Paeoniflorin concentration, test group rabbit after the administration in 6 hours in the blood Add up Paeoniflorin concentration in the blood of accumulative total Paeoniflorin concentration ratio control group rabbit in the blood remarkable increase is arranged. Pipering is described Can promote the absorption of Paeoniflorin in the rabbit intestines and stomach, increase blood concentration, be conducive to improve it after oral Bioavilability. Example two. the pipering extraction process
2.1 purpose: from black pepper, extract the high-purity pipering with the technology of optimizing.
2.2 method and result: Hainan pepper seed 200g, extract 2 times with 95% ethanol room temperature after pulverizing, Each each 2 days. The reduced pressure concentration extract, remove ethanol after, medicinal extract is dissolved in ether, with 5% NaOH Solution washing 2 times is again through washing 2 times. Reduced pressure concentration ether part is scattered in medicinal extract in the water, uses second Acetoacetic ester extraction 6 times, the combined ethyl acetate part, concentrate as for, methanol crystallization namely gets pipering crude product 5g, Yield is 2.5%.
Product launches the two R through doing the TLC contrast with the pipering standard items with 3 kinds of different solventsfValue all Identical; The ESI-MS determining molecular weight is m/z:285, coincide with pipering. The HPLC normalization method records purity 80%.
See accompanying drawing 3 2.3 extract flow chart.
2.4 attached: the preparation of pipering standard items
Get above-mentioned pipering crude product 20mg, usefulness purification by silica gel column chromatography behind the 40mg silica gel mixed sample (silica gel 200～300 orders, 3g; Eluant, eluent: benzinum-acetone=3: 1). TLC detects, and is merged into the outflow of single spot Thing is evaporated to driedly, and alcohol crystal gets faint yellow acicular crystal 7mg. Example three. the extraction process of Chinese herbaceous peony Glycyrrhiza uralensis compound
3.1 purpose: preparation Chinese herbaceous peony Glycyrrhiza uralensis compound extract, requiring content of paeoniflorin is 55%, Paeoniflorin: glycyrrhizic acid is 10: 1 (weight ratio)
3.2 material: Paeoniflorin standard items and glycyrrhizic acid standard items are available from Sichuan Province medicine inspecting institute; The river root of herbaceous peony and northeast Each two batches in Radix Glycyrrhizae is all available from lotus pond Chinese medicine market, Chengdu. Through identifying that two batches of river root of herbaceous peonys and northeast Radix Glycyrrhizae are respectively All belong to same kind. Detect through HPLC, content of paeoniflorin is respectively in the 1st batch and the 2nd batch of river root of herbaceous peony 2.10% and 5.74%, the 1 batch and the 2nd batch of northeast Radix Glycyrrhizae acid content are respectively 2.96% and 4.30%.
3.3 method and result:
3.3.1 the technique for extracting mixed flow process is seen accompanying drawing 4.
3.3.2 investigate the yield of this technique for extracting mixed, divide the river root of herbaceous peony and the northeast of getting respectively Different Weight for 4 times Extract 4 batches after Radix Glycyrrhizae mixes, the results are shown in Table 2.
Table 2: the yield batch medicinal material mixed extract of Chinese herbaceous peony Glycyrrhiza uralensis compound mixed extract under selected extraction process condition
Root of herbaceous peony Paeoniflorin Radix Glycyrrhizae glycyrrhizic acid weight Paeoniflorin glycyrrhizic acid
G content % g g content % g g g content % recovery rate % g content % recovery rate % 1 900 2.10 18.90 15 4.30 0.65 21.15 13.25 62.66 70.13 0.41 1.91 63.45 2 600 2.10 12.60 75 4.30 3.23 16.05 8.95 55.78 71.01 2.04 12.71 63.18 3 300 2.10 6.30 150 4.30 6.45 11.40 4.41 38.68 69.97 4.11 35.86 63.65 4 900 5.74 64.80 75 2.96 2.22 82.95 45.66 55.05 70.52 1.40 1.69 63.27 3.3.3 can be drawn the following conclusions by the above-mentioned four crowdes results that mix extraction that feed intake:
1. use selected technique for extracting mixed flow process, in every batch of extract, the yield of Paeoniflorin and glycyrrhizic acid Respectively basic identical, average yield is respectively 70.41% and 63.39%,, can think constant.
2. the weight of the active ingredient of each medicinal material and ratio each other in the Chinese medicine compound are before feeding intake and carry To change after getting. This variation and each medicinal material separately receipts in fixing compound technique for extracting mixed flow process Rate is relevant. 3.3.4 press content and the yield in selected technique for extracting mixed of ingredients active ingredient in the Chinese medicine compound Determine the checking of the prescription method of Chinese medicine compound:
In order to prepare Chinese herbaceous peony Glycyrrhiza uralensis compound extract, the percentage composition that requires Paeoniflorin in the extract is 55%, And the weight ratio of Paeoniflorin and glycyrrhizic acid is Paeoniflorin: glycyrrhizic acid=10: 1. When adopting the 2nd batch of medicinal material, it is white to establish the river The inventory of Chinese herbaceous peony is 500g, and (unit of weight in the following formula is equal by following formula calculating for mixed extract weight Be g):
Extract weight=(Paeoniflorin percentage composition in Chinese herbaceous peony medicinal material weight * Chinese herbaceous peony medicinal material * selected mixing extracts The yield of Paeoniflorin in the technology) Paeoniflorin percentage composition in the ÷ extract=(500 * 3.74% * 70%) ÷ 55%=23.8g.
And the inventory of northeast Radix Glycyrrhizae is calculated by following formula:
The inventory of northeast Radix Glycyrrhizae the=(percentage composition of Paeoniflorin * mixed extract weight * Chinese herbaceous peony in the mixed extract The ratio of glycyrrhizic acid in the weight ratio of medicine glucoside and glycyrrhizic acid) ÷ (Paeoniflorin in the weight ratio of Paeoniflorin and glycyrrhizic acid Ratio * licorice medicinal materials in the percentage composition * selected technique for extracting mixed of glycyrrhizic acid glycyrrhizic acid yield=(55% * 23.8 * 10) ÷ (100 * 2.96% * 63%)=70.20g.
Take by weighing river root of herbaceous peony 500g and northeast Radix Glycyrrhizae 70.20g, be cut into 1-3mm thickness, by above-mentioned selected mixing Close extraction process and extract, the actual extract 24.35g that obtains detects and calculates Chinese herbaceous peony in the extract through HPLC Salidroside content is 13.12g, content of paeoniflorin ÷ extract weight in compound mixed extract percentage composition=extract=13.12/24.35=53.88%. The content that detects and calculate glycyrrhizic acid in the extract through HPLC is 1.31g, Glycyrrhizic acid content ÷ extract weight=1.31/24.35=5.38% in percentage composition=extract in extract. Carry Get Paeoniflorin in the thing: glycyrrhizic acid=13.12: 1.31=100: 9.98. 3.4 conclusion:
The result has reached expected results, illustrates that this example adopts new prescriptions of traditional Chinese medicine side proposed by the invention Method is feasible and controlled. Example four is used the Chinese herbaceous peony licorice of content of paeoniflorin 53.88%, glycyrrhizic acid content 5.38%, and pepper Alkali content is 80.00% piperine extract, is prepared into capsule, every heavy 300mg of content, and every contains Paeoniflorin 150mg, glycyrrhizic acid 15mg, pipering 1.5mg. 1000 prescription is as follows: Extract weight (g) Chinese herbaceous peony Glycyrrhiza uralensis compound mixed extract 278.40 Piperine extract 1.88 PVP K30 19.72
The compound composition is mixed, sieve, detect homogeneity and meet the requirements, fill then hard capsules.
According to the standard described in the pharmacopeia and method, to purity and the content thereof of Paeoniflorin, glycyrrhizic acid and pipering Detect analysis with the index under the capsule item, the result meets the requirements.
By the method for example one, use herbal mixture capsule of the present invention and the capsule of removing pipering, to 10 Healthy premenopausal volunteers is tested, and is divided into two groups, 5 of test groups, and 4 of oral herbal mixture capsules of the present invention, 5 of control groups, 4 of the oral capsules of removing pipering found that it is dense that average Paeoniflorin blood medicine is organized in test Degree is significantly higher than the average Paeoniflorin blood concentration of control group (P＜0.01) Example five is used the Chinese herbaceous peony licorice of content of paeoniflorin 53.88%, glycyrrhizic acid content 5.38%, and pepper Alkali content is 80.00% piperine extract, is prepared into the afterbirth sheet, every heavy 300mg of content, every Contain Paeoniflorin 150mg, glycyrrhizic acid 15mg, pipering 1.5mg. 1000 prescription is as follows: Extract weight (g) Chinese herbaceous peony Glycyrrhiza uralensis compound mixed extract 278.40 Piperine extract 1.88 PVP K30 10.72 Dolomol 1.5 Sucrose dressing material 7.5 The compound composition is mixed, sieve, detect homogeneity and meet the requirements, then compressing tablet.
According to the standard described in the pharmacopeia and method, to purity and the content thereof of Paeoniflorin, glycyrrhizic acid and pipering Detect analysis with the index under the tablet item, the result meets the requirements. By the method for example one, use herbal mixture coating tablet of the present invention and the coating tablet of removing pipering, to 10 Healthy premenopausal volunteers is tested, and is divided into two groups, 5 of test groups, oral herbal mixture coating tablet 4 of the present invention Sheet, 5 of control groups, 4 of the oral coating tablets of removing pipering found that average Paeoniflorin is organized in test Blood concentration is significantly higher than the average Paeoniflorin blood concentration of control group (P＜0.05) Example six is used the Chinese herbaceous peony licorice of content of paeoniflorin 53.88%, glycyrrhizic acid content 5.38%, and pepper Alkali content is 80.00% piperine extract, is prepared into granule, and the heavy 5g of every bag content whenever comprises Chinese herbaceous peony Medicine glucoside 300mg, glycyrrhizic acid 30mg, pipering 3mg. The prescription of 1000 bags is as follows: Extract weight (g) Chinese herbaceous peony Glycyrrhiza uralensis compound mixed extract 556.80 Piperine extract 3.76 Sucrose 2000 Dextrin 2000 Starch 200 Hydroxypropyl cellulose 239.44 The compound composition is mixed, sieve, granulate, detect homogeneity, meet the requirements, then packed.
According to the standard described in the pharmacopeia and method, to purity and the content thereof of Paeoniflorin, glycyrrhizic acid and pipering Detect analysis with the index under the granule item, the result meets the requirements. By the method for example one, use herbal mixture particle of the present invention and the particle of removing pipering, to 10 health The volunteer tests, and is divided into two groups, 5 of test groups, and 2 bags of oral herbal mixture particles of the present invention, right According to 5 of groups, 2 bags of the oral particles of removing pipering found that average Paeoniflorin blood concentration is organized in test Be significantly higher than the average Paeoniflorin blood concentration of control group (P＜0.01) Example seven is used the Chinese herbaceous peony licorice of content of paeoniflorin 53.88%, glycyrrhizic acid content 5.38%, and pepper Alkali content is 80.00% piperine extract, is prepared into oral liquid, and every bottle of content volume is 10ml, and is every Bottle contains Paeoniflorin 300mg, glycyrrhizic acid 30mg, pipering 3mg. 1000 bottles prescription is as follows: Extract weight (g) Chinese herbaceous peony Glycyrrhiza uralensis compound mixed extract 556.80 Piperine extract 3.76 50% simple syrup is to 10000ml Annotate: oral liquid contains 0.3% Sodium Benzoate
The preparation of compound composition is distributed into oral liquid.
According to the standard described in the pharmacopeia and method, to purity and the content thereof of Paeoniflorin, glycyrrhizic acid and pipering Detect analysis with the index under the oral solutions item, the result meets the requirements. By the method for example one, use herbal mixture oral liquid of the present invention and the oral liquid of removing pipering, to 10 Healthy premenopausal volunteers is tested, and is divided into two groups, 5 of test groups, oral herbal mixture oral liquid 2 of the present invention Bottle, 5 of control groups, 2 bottles of the oral oral liquids of removing pipering found that average Paeoniflorin is organized in test Blood concentration is significantly higher than the average Paeoniflorin blood concentration of control group (P＜0.01)
Claims (6)
1. a herbal mixture that increases the paeoniflorin bioavailability is characterized in that, contains paeoniflorin and piperine in this herbal mixture.
2. herbal mixture according to claim 1 is characterized in that, the percentage by weight of paeoniflorin is 50%-99.99%, and the percentage by weight of piperine is 0.01%-50%.
3. herbal mixture according to claim 1 is characterized in that, contains glycyrrhizic acid in the herbal mixture, three flavor Effective Components of Chinese Herb percentage by weights are respectively, paeoniflorin 5%-99%, glycyrrhizic acid 5%-99%, the percentage by weight of piperine are 0.01%-30%.
4. according to the preparation of the herbal mixture in claim 1 or 2 or 3, it is characterized in that dosage form can be capsule, oral liquid, granule, tablet, syrup, tincture, membrane and effervescent.
5. the preparation method of a production such as claim 1 or 2 or 3 described herbal mixtures, it is characterized in that, requirement according to the dosage of each effective ingredient in the Chinese traditional compound medicine and the ratio between them, during mixed extraction, according to each content of effective in the raw medicinal herbs and the yield in certain technique for extracting mixed, determine the weight of each raw medicinal herbs, take by weighing constant weight then, mix, extract.
6. preparation method according to claim 5, it is characterized in that, the prescription method of herbal mixture is a weight of calculating the Chinese medicine raw medicinal herbs of respectively distinguishing the flavor of in the yield of the ratio of effective ingredient specific in each flavor Chinese medicine raw medicinal herbs and selected extraction process, writes out a prescription after the weighing respectively then.
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Owner name: CHONGQING LAIMEI PHARMACY CO., LTD. Free format text: FORMER OWNER: YAOYOU SCIENCE AND TECHNOLOGY DEVELOPMENT CO., LTD., CHENDU CITY Effective date: 20080411 |
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