CN103860545A - Use of arctigenin in preparing medicine for treating autoimmune hepatitis - Google Patents
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Abstract
The invention provides a use of arctigenin in preparing a medicine for treating autoimmune liver diseases, and belongs to the field of medicine. Arctigenin is an effective traditional Chinese medicine monomer obtained by extracting from a traditional Chinese medicine fructus arctii; when being used in treatment of the autoimmune liver diseases, arctigenin can significantly improve the proportion of immune cell factors of a patient, significantly reduces the aminotransferase level and the liver index of the patient, thereby playing effects of simultaneous treatment of principal and subordinate symptoms on the autoimmune liver diseases especially autoimmune hepatitis. Arctigenin has small toxic and side effect in a drug use process, and is definite in therapeutic effect, low in price and quite wide in medical application prospects.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of medical usage of arctigenin, be specifically related to the purposes of arctigenin in preparation treatment autoimmunity aglycon medicine.
Background technology
Autoimmune liver disease is a class autoimmune disease of the damage organ take liver as relative specificity immunopathogenesis.Along with the raising of understanding and diagnostic level, report that autoimmune liver disease prevalence raises year by year both at home and abroad, thereby more and more come into one's own and pay close attention to.It mainly comprises: any overlap syndrome between the two in autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis and this three kinds of diseases, often merge the outer immune disease of liver simultaneously, its diagnosis Main Basis specificity is biochemical abnormal, autoantibody and stem organization's feature.Wherein autoimmune hepatitis is the most common, and its hepatic tissue changes consistent with chronic viral hepatitis, but HBV Immunological Markers feminine gender.
Autoimmune hepatitis is the chronic progressive external inflammation disease being mediated by autoimmune response, its Clinical symptoms is serum transaminase rising, hypergammaglobulinemia, autoantibodies in various degree, histologic characteristics is that serious case can rapid progress be liver cirrhosis and liver failure take lymphocyte, plasmocyte infiltrating as main interface hepatitis.This disease worldwide all has generation, relatively high at American-European countries's sickness rate, it be unclear that, but the case load of domestic literature report is obvious ascendant trend at its definite sickness rate of China and prevalence.
The clinical manifestation of autoimmune hepatitis is very similar to viral hepatitis, and normal and viral hepatitis is obscured, but both treatments are far different.The Therapeutic Method of autoimmune hepatitis mainly contains Drug therapy and two kinds of methods of liver transplantation at present.Wherein liver transplantation is the effective ways that are used for the treatment of autoimmune hepatitis liver cirrhosis in whole latter stage, after liver transplantation most of patients after liver transplantation in 1 year autoantibody turn out cloudy, hypergammaglobulinemia is alleviated, and patient's survival rate all significantly rises.But postoperative have autoimmune hepatitis to recur, and particularly before liver transplantation, has fulminant hepatic failure Patients on Recurrence rate higher, and the somewhat expensive of liver transplantation, and therefore current Drug therapy remains the first-selection of current treatment autoimmune hepatitis.Alone prednisone therapy is suitable for that leukocyte obviously reduces, gestation, the tumor that occurs together or thiopurine methyltransferase handicapped, or the person that only needs brachytherapy.It is unstable or have hyperpietic's a diagnosis of autoimmune hepatitis that prednisone and azathioprine conjoint therapy are applicable to postmenopausal women, osteoporosis, brittle diabetes, obesity, acne, psychology.Glucocorticoid and ciclosporin A, tacrolimus, budesonide are also usually used in the replacement therapy of autoimmune hepatitis.But mournful, above-mentioned medicine all can not be satisfactory to the clinical therapeutic efficacy of autoimmune hepatitis, and the toxic and side effects of chemicals and high therapeutical effect usually make patient suffering can't bear.Therefore find at present the medicine that therapeutic effect is good, toxic and side effects is little, cheap and remain primary problem urgently to be resolved hurrily in autoimmune hepatitis treatment.
Fructus Arctii is the dry mature fruit of feverfew Fructus Arctii, is conventional Chinese medicine, has the function of dispelling wind and heat pathogens, lung qi dispersing rash, resolving toxin and disinhibiting the throat, for anemopyretic cold, cough with copious phlegm, measles, rubella, laryngopharynx swelling and pain, itch cheek erysipelas, carbuncle sore tumefacting virus.This Chinese medicine contains Lignanoids compounds, is mainly Arctiin (arctiin) and arctigenin (arctigenin) etc.Now existing evidence proves that arctigenin has stronger biological activity than Arctiin, such as antibacterial, antiviral, antitumor, anti-paf receptor and calcium antagonistic activity significantly, but prior art is not still reported the application of arctigenin in preparation autoimmune hepatitis medicine.
Summary of the invention
The invention provides a kind of autoimmune hepatitis medicine, select for clinical diagnosis of autoimmune hepatitis provides a kind of new medication.The active component of medicine of the present invention is arctigenin, arctigenin is from Chinese medicine Fructus Arctii, to extract the effective Chinese medicine monomer obtaining, now verify it and there is clinically multi-medicament activity, it has while treatment for autoimmune hepatitis, and therapeutic effect is outstanding, the little and cheap feature of toxic and side effects, has wide medical applications prospect.
The present invention relates to a kind of new medical usage of arctigenin, i.e. the purposes of arctigenin in preparation treatment autoimmune hepatitis medicine.Drug effect embodiment 11 of the present invention proves that arctigenin can regulate the disorder between the cytokine of rats with autoimmune hepatitis, be embodied in significantly leukocyte increasing Jie element 2 and gamma interferon level, and can significantly reduce the level of interleukin-4 and interleukin-4, thereby root, significantly reduce liver tissue injury.Drug effect embodiment 12 of the present invention proves that arctigenin can reduce the transaminase's of rats with autoimmune hepatitis content and liver index, thereby to playing significant treatment and preventive effect, its Drug therapy is evident in efficacy is better than existing medicine prednisone.
When in the present invention, arctigenin is for autoimmune hepatitis, administration object can be animal or human, route of administration can be selected suitable mode according to patient's the state of an illness and tolerance degree, preferably adopt oral, injection system administration, the dosage of arctigenin can change with administration object or route of administration difference.When in the present invention, arctigenin is for autoimmune hepatitis and applicable object behaviour, the consumption of arctigenin is 0.01mg/kgd~100mg/kgd, and further preferably the consumption of arctigenin is 0.016mg/kgd~0.16mg/kgd.The dosage of other animals can convert and obtain according to the body surface area ratio of man and animal, and this is that appearance is facile to those skilled in the art.
The present invention also provides the pharmaceutical preparation that comprises arctigenin that is suitable for above-mentioned medical usage.Specifically, the pharmaceutical preparation that comprises arctigenin described in can be oral formulations, sublingual administration preparation or injection.Oral formulations is as tablet, capsule, granule, Sublingual tablet, slow releasing tablet etc., and ejection preparation is as injectable powder, injection.The above-mentioned pharmaceutical preparation that comprises arctigenin all can adopt the conventional preparation technology of this kind of dosage form to prepare.
The present invention is suitable in the pharmaceutical preparation of said medicine purposes, and described arctigenin injection is preferably the subcutaneous injection agent that is applicable to subcutaneous administration, and wherein in each subcutaneous injection agent, the content of arctigenin is preferably 0.1mg-10mg.The agent of above-mentioned arctigenin subcutaneous injection is made up of arctigenin, cosolvent and/or water for injection.As a kind of embodiment preferred for this invention, inventor provides a kind of formula of the arctigenin injection that is applicable to subcutaneous injection administration, and this subcutaneous injection agent is made up of the component of following weight portion:
Arctigenin 5-50 part
Cosolvent 2-5 part
0.9% sodium chloride solution or water for injection are appropriate
Wherein said cosolvent is selected from one or more in tween 80, propylene glycol, glycerol, ethanol and PEG-400.The pH value of the above-mentioned subcutaneous injection agent that comprises arctigenin is 2.5-6.5, is preferably 3.0-4.0.For the acid-base modifier that regulates arctigenin subcutaneous injection agent pH value be citric acid, aminoacid, sodium hydroxide, hydrochloric acid, sodium bicarbonate one or more.
The present invention is suitable in the pharmaceutical preparation of said medicine purposes, and the oral formulations of described arctigenin is preferably arctigenin sublingual lozenge.Sublingual lozenge is owing to passing through mucosa delivery, and drug absorption is rapid, and drug effect speed is fast, and bioavailability is high.In described arctigenin sublingual lozenge, in each preparation unit, the content of arctigenin is 0.1-200mg.Above-mentioned arctigenin sublingual lozenge can also be prepared into Sublingual slow releasing tablet according to the needs of medication effect and the state of an illness, and it can extend the therapeutic effect of arctigenin to autoimmune hepatitis.
The present invention uses arctigenin to be used for autoimmune hepatitis medicine, compared with prior art has following advantage:
1. determined curative effect when arctigenin of the present invention is for autoimmune hepatitis treatment, not only can reduce liver transaminase content and liver index, more can regulate unbalance between lymphocyte cytokine, reduce the damage to hepatic tissue, play the effect for the treatment of both the principal and secondary aspects of a disease.Drug effect embodiment 11 of the present invention proves that arctigenin can regulate the disorder between the cytokine of rats with autoimmune hepatitis, be embodied in significantly leukocyte increasing Jie element 2 and gamma interferon level, and can significantly reduce the level of interleukin-4 and interleukin-4, thereby root, significantly reduce liver tissue injury.Drug effect embodiment 12 of the present invention proves that arctigenin can reduce the transaminase's of rats with autoimmune hepatitis content and liver index, thereby to playing significant treatment and preventive effect, its Drug therapy is evident in efficacy is better than existing medicine prednisone.
2. arctigenin is the natural drug monomer extracting from Chinese medicine Fructus Arctii, not only determined curative effect, and also toxic and side effects is very low, can significantly improve patient's compliance and the therapeutic effect of raising medicine.
3. cheap when arctigenin is for prevention or treatment autoimmune hepatitis, quality control is simple and convenient, and cost is low compared with existing biological preparation, can significantly reduce the medical expense of diagnosis of autoimmune hepatitis.
The specific embodiment
Further describe the present invention by specific embodiment below, but those skilled in the art should know, the embodiment of the present invention does not also limit the present invention in any way.
Embodiment 1 arctigenin injection
Prescription:
Arctigenin 10g
PEG-400 2g
0.9% sodium chloride solution adds to 10L
Preparation technology:
The PEG-400 of recipe quantity is added to arctigenin, and stirring and dissolving, adds 0.9% sodium chloride solution of recipe quantity, stirs, and citric acid is adjusted PH to 3, adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 2 arctigenin injections
Prescription:
Arctigenin 10g
PEG-400 3g
0.9% sodium chloride solution adds to 10L
Preparation technology:
The PEG-400 of recipe quantity is added to arctigenin, and stirring and dissolving, adds 0.9% sodium chloride solution to 10L, stirs, and citric acid is adjusted PH to 4, adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.Embodiment 3 arctigenin injections
Prescription:
Arctigenin 10g
PEG-400 1g
Water for injection adds to 10L
Preparation technology:
The PEG-400 of recipe quantity is added to arctigenin, and stirring and dissolving, adds water for injection to 10L, stirs, and citric acid is adjusted PH to 6.5, adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 4 arctigenin injections
Prescription:
Arctigenin 20g
PEG-400 4g
Water for injection adds to 10L
Preparation technology:
The PEG-400 of recipe quantity is added to arctigenin, and stirring and dissolving, adds water for injection to 10L, stirs, and citric acid is adjusted PH to 2.5, adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 5 arctigenin injections
Prescription:
Arctigenin 10g
PEG-400 3.3g
Water for injection adds to 10L
Preparation technology:
The PEG-400 of recipe quantity is added to arctigenin, and stirring and dissolving, adds water for injection to 10L, stirs, and citric acid is adjusted PH to 3, adds 0.5% needle-use activated carbon, stirs, and de-charcoal, to obtain final product.
Embodiment 6 arctigenin sublingual lozenges
Preparation technology: pretreatment is dried, pulverized and sieved to principal agent and each adjunct ingredient, principal agent and sugar, lactose, sodium carboxymethyl cellulose are mixed, using pure water as binding agent, the material mixing is prepared to soft material, cross 20 mesh sieves granulations and the dry granule of dry preparation under 60 degree, magnesium stearate is joined to above-mentioned dry granule always mixed, tabletting and get final product.
Embodiment 7 arctigenin slow releasing tablet
Preparation technology: said components dries, pulverize and sieve and mix direct compression after pretreatment and make.
Embodiment 8 arctigenin capsules
Preparation technology: conventional preparation technology is prepared from by capsule.
Embodiment 9 arctigenin tablets
Preparation technology: the preparation technology of tablet prepares routinely.
Embodiment 10 arctigenin slow releasing tablets
Preparation technology: be prepared into slow releasing tablet by the preparation technology of slow releasing tablet.
The therapeutical effect of embodiment 11 arctigenins to rats with autoimmune hepatitis
There is significant immunologic balance imbalance in rat models of autoimmune hepatitis, showing as CD4+ cell percentage ratio increases, Th2 cytokine levels raises, and Thl cytokine levels reduces and hepatocyte specificity lipoprotein antibody level raises, and causes the generation of autoimmune hepatitis.Wherein CD4+ cell infiltrates in hepatic tissue, discharge damage and can cause hepatic injury, Thl and Th2 cytoactive and cytokine balance imbalance thereof are the one of the main reasons that causes autoimmunity tissue injury, and when IL-6 promotes inflammatory reaction, acute phase protein release is also the reason that causes liver tissue injury.
1. the preparation of rat models of autoimmune hepatitis:
Wistar rat, male, 3 monthly ages.Adopt Freund's complete adjuvant only to add hepatocyte specificity lipoprotein 2mg/, subcutaneous and abdominal cavity and muscle multi-point injection in cervical region, axillary fossa, groin, every some 0.2mL, 10d/ time, injects after 2 times continuously, change hepatocyte specificity lipoprotein 1mg (not adding Freund's complete adjuvant) above-mentioned position multi-point injection into, 1 time/week, change 1 time/month into after injecting 3 times, then inject 3 times, and after last 1 immunity the 3rd day, strengthen 1 time with hepatocyte specificity lipoprotein 2mg intravenous injection.In strengthening latter the 3rd day, produce at random 3 and do liver histopathology inspection, result shows: the animal liver cell degeneration necrosis through the immunity of hepatocyte specificity lipoprotein is more obvious, moderate piecemeal necrosis, there is bridging necrosis, in lobule, have fibrous septum to form, prompting experimental autoimmune hepatitis model is successful.
2, administration and grouping
Successful modeling rats with autoimmune hepatitis is divided into following 6 groups at random, 10 every group.Each administration group administration situation is as follows:
Normal group: the isopyknic solvent of subcutaneous injection;
Model group: the isopyknic solvent of subcutaneous injection;
Prednisone group: gavage gives the prednisone of 5mg/kg;
Arctigenin low dose group: medicine 0.5mg/kg prepared by the subcutaneous injection embodiment of the present invention 1;
Dosage group in arctigenin: medicine 1mg/kg prepared by the subcutaneous injection embodiment of the present invention 1;
Arctigenin high dose group: medicine 4mg/kg prepared by the subcutaneous injection embodiment of the present invention 1.
All administration group administrations every day 1 time, successive administration 3 weeks is got blood for subsequent use in the time that administration finishes, and measures the content of each cytokine in Peripheral Lymphocytes of Rat culture supernatant.
3, leading indicator is measured
Lymphocyte is cultivated and propagation: by animal Thiopental Anesthesia, routine disinfection, peels off skin of chest abdomen, opens thoracic cavity and abdominal cavity, heart extracting blood, and centrifugal 10min, separated plasma-60 ℃ preservation is standby surveys.Collecting cell, the culture medium suspension hemocyte of 3 times of volumes, cell suspension is slowly added in to lymphocyte separation medium upper strata, the centrifugal 20min of 500g, draw lymphocyte, Hank ' S liquid washing 3 times, precipitation suspends with culture fluid, counting, with culture medium adjustment cell to 1 × 10 that containing volume fraction are 0.15 calf serum and 10% rat self blood plasma
10l
-1, be inoculated in 24 well culture plates, the CO that 37 ℃, volume fraction are 0.05
2, former culture 4h, centrifugal, abandon supernatant, precipitation suspends by culture medium, and counting is adjusted cell to 1 × 10
9l
-1, be inoculated in 24 well culture plates.
The detection method of cytokine and step: adopt ELISA method, automatic enzyme immune instrument carries out detection by quantitative.First before use reagent is taken out to equilibrium at room temperature 30min from refrigerator.Reagent is shaken up, add the standard substance that 100 μ L doubly dilute, the diluent of sample or standard is in micropore, respectively as standard control, pattern detection or blank.Every hole adds the biotin labeling of 50 μ L dilutions to detect antibody, room temperature 3h, and the porose middle reactant liquor that inclines, washes plate 3 × 3min.Every hole adds the affinity element of horseradish peroxidase (HRP) labelling, and room temperature leaves standstill 30min, and every hole adds tetramethyl benzidine (TMB) solution 100 μ L, lucifuge 10~15min, colour developing.Every hole adds the sulphuric acid cessation reaction of 100 μ L 1.8mol/L, detects absorbance at 450nm wavelength place.
4, data statistics and interpretation of result
Statistical analysis adopts SPSS 13.0 statistical analysis software deal with data, and result represents with x ± s, the relatively employing t check of group difference.
The impact of table 1 arctigenin on rat models of autoimmune hepatitis periphery lymphocyte factor level
Group | n | Interleukin II | Interleukin-4 | Interleukin-6 | Gamma interferon |
Normal group | 12 | 75.14±7.49 | 58.97±6.64 | 259.46±24.18 | 364.15±31.73 |
Model group | 12 | 43.15±5.16 ** | 86.49±7.95 ** | 435.16±37.84 ** | 227.48±20.64 ** |
Prednisone group | 12 | 47.16±6.42 | 82.29±6.35 | 421.41±30.17 | 245.17±25.42 & |
High group of arctigenin | 12 | 68.25±5.48 &&## | 61.31±6.24 &&## | 315.27±31.25 &&## | 347.62±27.45 &&## |
Group in arctigenin | 12 | 58.16±5.06 &# | 68.18±6.89 &# | 374.19±37.18 &&## | 279.49±25.39 &&# |
Low group of arctigenin | 12 | 52.31±5.12 & | 74.27±7.16 & | 405.86±35.19 & | 246.53±26.67 & |
Compared with Normal group,
*p < 0.01; Compared with model group,
aMP.AMp.Ampp < 0.05,
aMP.AMp.Amp &p < 0.01
Compared with prednisone group,
#p < 0.05,
##p < 0.01.
As can be seen from Table 1, model group interleukin II and gamma interferon level compared with normal group significantly reduce, and interleukin-4 and Interleukin-6 significantly raise.Compared with model group, prednisone group can aglycon
Improve interleukin level and gamma interferon level, change the ratio between cytokine, but change amplitude is little, no difference of science of statistics compared with model group.Compared with model group, the each dosage group of arctigenin can significantly be improved the proportional imbalance between interleukin level and gamma interferon level, be in particular in its significantly leukocyte increasing Jie element 2 and gamma interferon level (P < 0.05), significantly reduce the level (P < 0.05) of interleukin-4 and interleukin-6.Arctigenin is presenting dose dependent aspect the proportional imbalance improving between interleukin level and gamma interferon level, and wherein each cytokine levels of the high group of arctigenin has utmost point significant difference (P < 0.01) compared with model group.
The impact of embodiment 12 arctigenins on rats with autoimmune hepatitis liver function and liver index
The preparation of 1 experimental autoimmune hepatitis model
Wistar rat, male, 3 monthly ages.Adopt Freund's complete adjuvant only to add hepatocyte specificity lipoprotein 2mg/, subcutaneous and abdominal cavity and muscle multi-point injection in cervical region, axillary fossa, groin, every some 0.2mL, 10d/ time, injects after 2 times continuously, change hepatocyte specificity lipoprotein 1mg (not adding Freund's complete adjuvant) above-mentioned position multi-point injection into, 1 time/week, change 1 time/month into after injecting 3 times, then inject 3 times, and after last 1 immunity the 3rd day, strengthen 1 time with hepatocyte specificity lipoprotein 2mg intravenous injection.In strengthening latter the 3rd day, produce at random 3 and do liver histopathology inspection, result shows: the animal liver cell degeneration necrosis through the immunity of hepatocyte specificity lipoprotein is more obvious, moderate piecemeal necrosis, there is bridging necrosis, in lobule, have fibrous septum to form, prompting experimental autoimmune hepatitis model is successful.
2 grouping and administrations
Rat model adaptability was raised after 1 week, was divided at random normal group, model group and administration group, and specifically grouping situation sees the following form, 10 every group.Every afternoon is gavage medicine when 14:30, and dosage is as follows:
Normal group: the sodium carboxymethyl cellulose of same volume;
Model control group: the sodium carboxymethyl cellulose of same volume;
Prednisone group: gavage gives 5mg/ (kg.d) prednisone;
Arctigenin low dose group: Sublingual gives to prepare arctigenin tablet 0.1mg/ (kg.d) by embodiment 6;
Dosage group in arctigenin: Sublingual gives to prepare arctigenin tablet 1mg/ (kg.d) by embodiment 6;
Arctigenin high dose group: Sublingual gives to prepare arctigenin tablet 10mg/ (kg.d) by embodiment 6.
3 detect index
Press above-mentioned administering mode successive administration 14 days, after last administration, pentobarbital sodium anesthetized rat, dissects, and abdomen cardinal vein is got hematometry biochemical indicator, gets liver and weighs.
3.1. liver function
Result of the test shows (referring to table 2), model group rat blood serum ALT, AST content significantly raise compared with normal group, the rat blood serum ALT of each administration group, the obvious decline compared with model group of AST content, especially, the each dosage group of arctigenin has utmost point significant difference compared with model group, have significant difference compared with prednisone group, this explanation arctigenin is better than prednisone group in the prevention to rat autoimmune hepatitis or treatment.
The impact of table 2 arctigenin on rat model liver function
With model group comparison,
*p < 0.05; With model group comparison,
*p < 0.01;
With the comparison of prednisone group,
#p < 0.05; With the comparison of prednisone group,
##p < 0.01
3.2. liver index
Result of the test shows (referring to table 3), model group rats'liver index has utmost point significant difference compared with normal group, the liver index of the rat of each administration group has utmost point significant difference compared with model group, especially, the each dosage group of arctigenin has significant difference or utmost point significant difference compared with prednisone group, and this explanation arctigenin reduces liver index and is significantly better than existing medicine prednisone rat experimental autoimmune hepatitis model treatment is focused on.
The impact of table 3 arctigenin on Rats Organs and Tissues index
With normal group comparison,
$p < 0.05; With normal group comparison,
$$p < 0.01;
With model group comparison,
*p < 0.05; With model group comparison,
*p < 0.01;
With the comparison of prednisone group,
#p < 0.05; With the comparison of prednisone group,
##p < 0.01;
Claims (10)
1. the purposes of arctigenin in preparation treatment autoimmune hepatitis medicine.
2. purposes as claimed in claim 1, is characterized in that the people of arctigenin is 0.01mg/kgd~100mg/kgd by dosage.
3. purposes as claimed in claim 2, is characterized in that the people of arctigenin is 0.016mg/kgd~0.16mg/kgd by dosage.
4. the purposes as described in as arbitrary in claim 1-3, is characterized in that arctigenin is oral formulations, sublingual administration preparation or ejection preparation.
5. purposes as claimed in claim 4, is characterized in that the oral formulations of described arctigenin or sublingual administration preparation are tablet, capsule, granule.
6. purposes as claimed in claim 4, is characterized in that the content of arctigenin in the oral formulations of described arctigenin or each preparation unit of sublingual administration preparation is 0.1-200mg.
7. purposes as claimed in claim 4, the ejection preparation that it is characterized in that described arctigenin is subcutaneous injection agent.
8. purposes as claimed in claim 7, the content that it is characterized in that arctigenin in the agent of per unit subcutaneous injection is 0.1-10mg.
9. purposes as claimed in claim 7, is characterized in that the agent of described arctigenin subcutaneous injection is made up of following component:
Arctigenin 5-50 part
Cosolvent 2-5 part
0.9% sodium chloride solution or water for injection are appropriate;
Wherein said cosolvent is selected from one or more in tween 80, propylene glycol, glycerol, ethanol and PEG-400; The pH value of described subcutaneous injection agent is 2.5-6.5; For the acid-base modifier that regulates subcutaneous injection agent pH value be citric acid, aminoacid, sodium hydroxide, hydrochloric acid, sodium bicarbonate one or more.
10. purposes as claimed in claim 7, the pH that it is characterized in that the agent of described arctigenin subcutaneous injection is 3.0-4.0.
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CN104095844A (en) * | 2014-07-30 | 2014-10-15 | 重庆理工大学 | Application of arctigenin in preparation of drug for treatment of hepatic fibrosis or liver cirrhosis |
CN105601593A (en) * | 2015-12-24 | 2016-05-25 | 吉林农业大学 | Lignanolide composition for nitrite scavenger as well as preparation method and application of lignanolide composition |
CN109091520A (en) * | 2018-08-03 | 2018-12-28 | 西南民族大学 | The purposes of fructus arctii aerial part |
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CN101134031A (en) * | 2006-08-30 | 2008-03-05 | 山东绿叶天然药物研究开发有限公司 | Use of arctigenin in the preparation of medicament for treating and preventing chronic renal failure and kidney fibrosis |
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CN101134031A (en) * | 2006-08-30 | 2008-03-05 | 山东绿叶天然药物研究开发有限公司 | Use of arctigenin in the preparation of medicament for treating and preventing chronic renal failure and kidney fibrosis |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104095844A (en) * | 2014-07-30 | 2014-10-15 | 重庆理工大学 | Application of arctigenin in preparation of drug for treatment of hepatic fibrosis or liver cirrhosis |
CN105601593A (en) * | 2015-12-24 | 2016-05-25 | 吉林农业大学 | Lignanolide composition for nitrite scavenger as well as preparation method and application of lignanolide composition |
CN105601593B (en) * | 2015-12-24 | 2017-12-22 | 吉林农业大学 | Nitrite scavenger lignanolide composition and preparation method and application |
CN109091520A (en) * | 2018-08-03 | 2018-12-28 | 西南民族大学 | The purposes of fructus arctii aerial part |
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