CN1698805A - Application of snow lotus injection in medicine preparation for treating cazenaves lupus - Google Patents

Application of snow lotus injection in medicine preparation for treating cazenaves lupus Download PDF

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Publication number
CN1698805A
CN1698805A CN 200510073385 CN200510073385A CN1698805A CN 1698805 A CN1698805 A CN 1698805A CN 200510073385 CN200510073385 CN 200510073385 CN 200510073385 A CN200510073385 A CN 200510073385A CN 1698805 A CN1698805 A CN 1698805A
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preparation
injection
herba saussureae
saussureae involueratae
snow lotus
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张海峰
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Abstract

The invention relates to the use of snow lotus injection in medicine preparation in preparing medicament for treating lupus erythematosus. Pharmacological experiment shows that, the saussurea involucrate injection has very good effect for treating lupus erythematosus.

Description

The application of snow lotus injection preparation in preparation treatment lupus erythematosus medicine
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to the new purposes of snow lotus injection preparation, be i.e. the application of snow lotus injection preparation in preparation treatment lupus erythematosus medicine.
Technical background
Systemic lupus erythematosus (sle) (SLE) is a kind of autoimmune disease, and China has 1,000,000 patients approximately.Pathological changes is involved multisystem, many organs, has a strong impact on health, and multiple autoantibody appears in serum, and tangible immunologic derangement is arranged.Mutual complicated effects such as heredodiathesis, gonadal hormone and environmental factors cause the body's immunity disorder, cause the generation of SLE and continue, and make disease be difficult for alleviating, and the clinical change multiterminal cause the diagnosis and treatment difficulty, the mortality rate height.In treatment, mainly use glucocorticoid and immunosuppressant, but the side effect that brings thus makes patient's Abwehrkraft des Koepers low, easily causes infection, become three big one of the main reasons of SLE death.To subtract hormone in order removing smoothly, to alleviate the side effect of hormone and immunosuppressant, stablize the state of an illness, reduce recurrence, turn to Chinese traditional treatment by the simple western medicine treatment gradually clinically.
Herba Saussureae Involueratae is the wounded in the battle Herb that the continuous Saussurea Laniceps Hand.-Mazz. of feverfew, snow lotus of big bud flower have another name called Saussurea involucrata Saussurea involucrate Kar.et Kin., Saussurea medusa Maxim. Saussurea medusa Maxim. etc., has except that cold, tonifying YANG, regulating menstruation, hemostatic effect.Be used for sexual impotence, soreness of the waist and knees, women's metrorrhagia and leukorrhagia, menoxenia, rheumatic arthritis, traumatic hemorrhage.Contain flavonoid, Coumarins, anthraquinone class and sesquialter card compounds in the Herba Saussureae Involueratae.
With the Herba Saussureae Involueratae is that the traditional medicine Injectio that raw medicinal material is prepared from has Herba Saussureae Involueratae injection [17 in Chinese medicine promulgated by the ministries or commissions of the Central Government] and freeze-dry snow lotus powder agent [application number CN02134078.1], has the effect of good anti-inflammatory analgesic, detumescence, blood circulation promoting and blood stasis dispelling.In data-searching, find no any report that is used for the treatment of lupus erythematosus about the snow lotus injection preparation.
Summary of the invention
Research worker of the present invention is selected rabbit Arthus reaction and rat assist agent arthritis model for use according to the pathogeny of SLE, with the snow lotus injection preparation is to be subjected to reagent to observe its influence to rabbit Arthus reaction, rat assist agent arthritis, and the snow lotus injection preparation has good therapeutical effect to SLE as a result.
The objective of the invention is the application of open snow lotus injection preparation in preparation treatment lupus erythematosus medicine.
Above-mentioned snow lotus injection preparation comprises Herba Saussureae Involueratae aqueous injection, Herba Saussureae Involueratae infusion solution, Saussurea involucrate powder injection and freeze-dry snow lotus powder agent.
The present invention is achieved by the following technical solutions:
One, pharmacodynamic experiment
Animal: Wistar rat and rabbit.
Medicine and reagent: the snow lotus injection preparation comprises: Herba Saussureae Involueratae injection [Xinjiang pharmaceutical factory], freeze-dry snow lotus powder agent [being prepared from] according to the method among the application number CN02134078.1, Herba Saussureae Involueratae infusion solution and Herba Saussureae Involueratae powder injection formulation [being prepared from according to the following method of the present invention] provide by Tianzhijiao Medication Development Co., Ltd., Guangdong; Prednisone, fairy house pharmaceutical Co. Ltd produces; Cyclophosphamide for injection, Hualian Pharmaceutical Co., Ltd., Shanghai produces; Freund ' s Freund's complete adjuvant: SIGMA company; Ovalbumin: SIGMA company; The reference of ovalbumin-Freund ' s Freund's complete adjuvant [Zhu Liping, etc.Immunology common experimental method.Beijing: People's Medical Officer Press, 2000:17-19] preparation; Blood plasma cortisol ria-determination box, IL-2 ria-determination box.
1, rabbit Arthus reaction test: get 30 of body weight (2.0 ± 0.2) kg healthy rabbits, male and female half and half, by [Xu Shuyun, etc.Pharmacological experimental methodology.Beijing: People's Health Publisher, 2002:1416-1417,920-921], every animal is intramuscular injection 1ml ovalbumin-Freund ' s Freund's complete adjuvant 1 time weekly, sensitization, continuous 4 weeks.Last sensitization rabbit on the same day is divided into 3 groups at random, i.e. normal saline group (model group), and cyclophosphamide group (5.0mg/kg) and Herba Saussureae Involueratae injection group (are equivalent to 5g crude drug/kg), 10 every group.Each group is pressed dosage shown in the table 1 in last sensitization intraperitoneal injection on the same day, continuous 10d, and tame rabbit back intradermal injection 1% ovalbumin (antigen attack) on the 10th, every some injection volume is 0.2ml.Observe following index: antigen is attacked back 2,4,8,12,24h observes the diameter of every some local skin redness; Antigen is attacked and respectively to be organized the rabbit femoral artery behind the 24h and get blood, press the Polyethylene Glycol method [Zhu Liping, etc.Immunology common experimental method.Beijing: People's Medical Officer Press, 2000:17-19] measure the content of circulating immune complex and press detection kit description time-and-motion study serum il-2 level.
The result: antigen is attacked the back different time, and there were significant differences than model group for the red and swollen diameter of Herba Saussureae Involueratae injection group rabbit skin of back, shows that Herba Saussureae Involueratae injection all can suppress rabbit Arthus reaction (seeing Table 1) in different time.Simultaneously, Herba Saussureae Involueratae injection group rabbit circulating immune complex and IL-2 level are than model group significantly descend (seeing Table 2).
The influence of table 1 pair rabbit Arthus reaction (X ± S)
Group Antigen is attacked the red and swollen diameter/cm of back different time skin of back
??2h ??4h ??8h ??12h ??24h
Model group Herba Saussureae Involueratae injection group cyclophosphamide group ??0.62±0.08 ??0.28±0.06 **??0.23±0.05 ** ??0.84±0.08 ??0.37±0.08 **??0.34±0.05 ** ??1.18±0.11 ??0.56±0.07 **??0.50±0.07 ** ??1.23±0.15 ??0.65±0.07 **??0.60±0.06 ** ??0.83±0.12 ??0.52±0.16 **??0.43±0.07 **
Annotate: compare with model group: *P<0.05, *P<0.01.
The influence of table 2 pair rabbit Arthus reaction rabbit anteserum immune complex and IL-2 content (X ± S)
Group Immune complex content IL-2 content/μ gL -1
Model group Herba Saussureae Involueratae injection group cyclophosphamide group ??0.25±0.06 ??0.17±0.04 **??0.15±0.03 ** ??8.34±2.88 ??1.86±0.87 **??1.15±0.66 **
Annotate: compare with model group: *P<0.05, *P<0.01.
2, to the influence of rat assist agent arthritis: 45 of Wistar male rats getting body weight (180 ± 20) g, 0.1ml causes inflammation with the right back sole of the foot intradermal injection Freund ' of every Mus s Freund's complete adjuvant, cause scorching back rat and be divided into 3 groups at random, be normal saline group (model group), prednisone group (0.04g/kg) and freeze-dry snow lotus powder agent group (are equivalent to 5g crude drug/kg), 15 every group.Each group is by the intraperitoneal injection on the 8th after causing inflammation of dosage shown in the table 3,21d continuously.Observe following index: survey the left back sole of the foot fixed position of rat Zhou Jing day by day after reaching before the injection adjuvant; Cause scorching back the 28th day, by the standards of grading evaluation arthritis index of " pharmacological experimental methodology "; Cause scorching back the 28th day, each is organized the rat broken end and gets blood, by detection kit description time-and-motion study blood plasma cortisol content and cut open get spleen, the adrenal gland weighs and asks organ index.
The result: freeze-dry snow lotus powder agent group left side swelling degree of the paw significantly is lower than model group, and arthritis index shows that than descending (seeing Table 3) the freeze-dry snow lotus powder agent can obviously suppress the rat assist agent arthritis secondary affection simultaneously.In addition, freeze-dry snow lotus powder agent group and model group relatively, index and spleen index significantly descends, adrenal gland's index, level of plasma cortisol significantly raise (seeing Table 4).
The influence of table 3 pair rat assist agent arthritis secondary affection (X ± S)
Group Cause scorching back different time left side swelling degree of the paw/cm Arthritis index
??8d ??16d ??24d ??28d
Model group freeze-dry snow lotus powder agent group prednisone group ??0.11±0.08 ??0.07±0.08 **??0.06±0.08 ** ??0.72±0.12 ??0.40±0.07 **??0.36±0.10 ** ??0.96±0.10 ??0.54±0.10 **??0.47±0.10 ** ??0.72±0.11 ??0.43±0.12 **??0.37±0.08 ** ??3.60±0.64 ??2.98±0.56 *??2.90±0.50 *
Annotate: compare with model group: *P<0.05, *P<0.01.
The influence of table 4 pair adjuvant arthritis rats spleen, adrenal gland and blood plasma cortisol (X ± S)
Group Index and spleen index (%) Adrenal gland's index (%) Blood plasma cortisol (μ g/L)
Model group freeze-dry snow lotus powder agent group prednisone group ??0.27±0.03 ??0.21±0.03 **??0.18±0.04 ** ??0.0174±0.0014 ??0.0198±0.0018 **??0.0136±0.0012 ** ??22.76±5.20 ??40.14±8.38 **??15.27±2.10 **
Annotate: compare with model group: *P<0.05, *P<0.01.
By above-mentioned pharmacodynamic experiment as can be seen, the snow lotus injection preparation has the effect of good treatment lupus erythematosus.
Two, preparation embodiment
Embodiment 1
Herba Saussureae Involueratae injection is prepared from according to the method for making in [17 in Chinese medicine promulgated by the ministries or commissions of the Central Government] 254 pages.
Embodiment 2
The freeze-dry snow lotus powder agent is prepared from according to the method in the patent documentation of application number CN02134078.1.
Embodiment 3
Get Herba Saussureae Involueratae medical material 10kg, pulverize, add 8 times of amount 70% ethanol and in microwave reactor, carry out reflux, extract,, temperature is controlled at 70 ℃, and power is 600W, extracts 3 times, each 30 minutes, merge extractive liquid, filters, and filtrate is reclaimed ethanol and is concentrated into solution with rotation knifing concentrating instrument at 50 ℃: medical material is 1: 1, leave standstill, filter, filtrate is crossed D101 type macroporous adsorptive resins, first washing with 4 times of amounts, 3 times of amounts of reuse, 90% ethanol elution, collect ethanol elution and reclaim ethanol at 50 ℃ with rotation knifing concentrating instrument, the concentrated solution thin up is to solution: medical material is 1: 1, is 10000 ultrafilter membrane ultrafiltration with molecular cut off, filtrate concentrates, drying is pulverized, and obtains Herba Saussureae Involueratae extract.
Getting Herba Saussureae Involueratae extract and dissolve with water for injection, is 8.0 with the meglumine adjust pH, and with 0.22 μ m filtering with microporous membrane, sterilization is prepared into 5000 of the hydro-acupuncture preparations of every 2ml.
Embodiment 4
Get Herba Saussureae Involueratae medical material 10kg, pulverize, add 8 times of amount 40% ethanol and in microwave reactor, carry out reflux, extract,, temperature is controlled at 50 ℃, and power is 400W, extracts 2 times, each 20 minutes, merge extractive liquid, filters, and filtrate is reclaimed ethanol and is concentrated into solution with rotation knifing concentrating instrument at 50 ℃: medical material is 1: 1, leave standstill, filter, filtrate is crossed polyamide column, first washing with 4 times of amounts, 5 times of amounts of reuse, 60% ethanol elution, collect ethanol elution and reclaim ethanol at 50 ℃ with rotation knifing concentrating instrument, the concentrated solution thin up is to solution: medical material is 1: 1, is 10000 ultrafilter membrane ultrafiltration with molecular cut off, filtrate concentrates, drying is pulverized, and obtains Herba Saussureae Involueratae extract.
Getting Herba Saussureae Involueratae extract and dissolve with water for injection, add sodium chloride or glucose accent etc. and ooze, is 6.0 with the meglumine adjust pH, with 0.22 μ m filtering with microporous membrane, sterilizes, and is prepared into 5000 bottles of the infusion preparations of every bottle of 100ml.
Embodiment 5
Get Herba Saussureae Involueratae medical material 10kg, pulverize, add 8 times of amount 50% ethanol and in microwave reactor, carry out reflux, extract,, temperature is controlled at 60 ℃, and power is 500W, extracts 2 times, each 30 minutes, merge extractive liquid, filters, and filtrate is reclaimed ethanol and is concentrated into solution with rotation knifing concentrating instrument at 50 ℃: medical material is 1: 1, leave standstill, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, first washing with 4 times of amounts, 4 times of amounts of reuse, 80% ethanol elution, collect ethanol elution and reclaim ethanol at 50 ℃ with rotation knifing concentrating instrument, the concentrated solution thin up is to solution: medical material is 1: 1, is 10000 ultrafilter membrane ultrafiltration with molecular cut off, filtrate concentrates, drying is pulverized, and obtains Herba Saussureae Involueratae extract.
Getting Herba Saussureae Involueratae extract and dissolve with water for injection, add polyvinylpyrrolidone, is 7.0 with the meglumine adjust pH, and with 0.22 μ m filtering with microporous membrane, drying is prepared into 5000 of powder injection formulations.
Embodiment 6
Get Herba Saussureae Involueratae medical material 10kg, pulverize, add 8 times of amount 60% ethanol and in microwave reactor, carry out reflux, extract,, temperature is controlled at 55 ℃, and power is 600W, extracts 3 times, each 20 minutes, merge extractive liquid, filters, and filtrate is reclaimed ethanol and is concentrated into solution with rotation knifing concentrating instrument at 50 ℃: medical material is 1: 1, leave standstill, filter, filtrate is crossed the NKA macroporous adsorbent resin, first washing with 4 times of amounts, 3 times of amounts of reuse, 70% ethanol elution, collect ethanol elution and reclaim ethanol at 50 ℃ with rotation knifing concentrating instrument, the concentrated solution thin up is to solution: medical material is 1: 1, is 10000 ultrafilter membrane ultrafiltration with molecular cut off, filtrate concentrates, drying is pulverized, and obtains Herba Saussureae Involueratae extract.
Get Herba Saussureae Involueratae extract and dissolve with water for injection, add mannitol, adjust pH is 6.5, and with 0.22 μ m filtering with microporous membrane, lyophilization is prepared into 5000 of freeze-dried powders.

Claims (3)

1, the application of snow lotus injection preparation in preparation treatment lupus erythematosus medicine.
2, snow lotus injection preparation according to claim 1 is Herba Saussureae Involueratae aqueous injection, Herba Saussureae Involueratae infusion solution, Saussurea involucrate powder injection.
3, snow lotus injection preparation according to claim 1, its preparation method may further comprise the steps:
(1) preparation of Herba Saussureae Involueratae extract
Get the Herba Saussureae Involueratae medical material, pulverize, add 8 times of amount 40-70% ethanol and in microwave reactor, carry out reflux, extract,, temperature is controlled at 50-70 ℃, and power is 400-600W, extracts 2-3 time, each 20-30 minute, merge extractive liquid, filters, and filtrate is reclaimed ethanol and is concentrated into solution with rotation knifing concentrating instrument at 50 ℃: medical material is 1: 1, leave standstill, filter, filtrate is crossed macroporous adsorbent resin or polyamide column, first washing with 4 times of amounts, reuse 3-5 doubly measures the 60-90% ethanol elution, collect ethanol elution and reclaim ethanol at 50 ℃ with rotation knifing concentrating instrument, the concentrated solution thin up is to solution: medical material is 1: 1, is 10000 ultrafilter membrane ultrafiltration with molecular cut off, filtrate concentrates, drying is pulverized, and obtains Herba Saussureae Involueratae extract.
(2) preparation of preparation
The preparation of hydro-acupuncture preparation: getting Herba Saussureae Involueratae extract and dissolve with water for injection, is 6.0-8.0 with the meglumine adjust pH, with 0.22 μ m filtering with microporous membrane, sterilizes, and is prepared into the hydro-acupuncture preparation of every 2ml.
The preparation of infusion preparation: getting Herba Saussureae Involueratae extract and dissolve with water for injection, add sodium chloride or glucose accent etc. and ooze, is 6.0-8.0 with the meglumine adjust pH, with 0.22 μ m filtering with microporous membrane, sterilizes, and is prepared into the infusion preparation of every bottle of 100ml.
The preparation of powder injection formulation: getting Herba Saussureae Involueratae extract and dissolve with water for injection, add the water-soluble injection pharmaceutic adjuvant, is 6.0-8.0 with the meglumine adjust pH, and with 0.22 μ m filtering with microporous membrane, drying is prepared into powder injection formulation.
CN 200510073385 2005-06-03 2005-06-03 Application of snow lotus injection in medicine preparation for treating cazenaves lupus Pending CN1698805A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102764286A (en) * 2012-07-17 2012-11-07 新疆天山莲药业有限公司 Method for separating and enriching total flavone and total polysaccharide in snow lotus extract powder
CN107582601A (en) * 2017-10-30 2018-01-16 罗天碧 A kind of medicine for treating lupus erythematosus and preparation method thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102764286A (en) * 2012-07-17 2012-11-07 新疆天山莲药业有限公司 Method for separating and enriching total flavone and total polysaccharide in snow lotus extract powder
CN102764286B (en) * 2012-07-17 2014-12-24 新疆天山莲药业有限公司 Method for separating and enriching total flavone and total polysaccharide in snow lotus extract powder
CN107582601A (en) * 2017-10-30 2018-01-16 罗天碧 A kind of medicine for treating lupus erythematosus and preparation method thereof

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