CN1981778A - Medicinal composition for self-immune diseases and organ transplantation exclusion - Google Patents
Medicinal composition for self-immune diseases and organ transplantation exclusion Download PDFInfo
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Abstract
A composite medicine for treating autoimmune disease and the rejection reaction after organ transplantation is prepared from orientvien stem, etc.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that is used for autoimmune disease and organ transplantation rejection, and its production and use.More specifically, the present invention relates to the immunosuppressive action of Caulis Sinomenii compound medicament composition, and the purposes of this compound medicament composition aspect treatment autoimmune disease and anti-organ transplantation rejection.
Background technology
To resist external invasion and attack such as pathogenic bacteria necessary though immunity is for everyone, yet the immunity that suppresses human body in some cases is favourable, for example treats autoimmune disease and suppresses the organ transplant rejection.
As the human immune system self component is taken place excessively to reply autoantibody or the autosensitization lymphocyte that is produced, damage self normal structure, and when causing corresponding symptoms, be called autoimmune disease.Common autoimmune disease has active chronic hepatitis, glomerulonephritis at present, and systemic lupus erythematosus (sle) or the like does not also have therapy measure now, is the disease of a class serious harm human health.To this class treatment of diseases, be primarily aimed at the pathological change of disease and the consequence due to the tissue injury and treat at present; Also can be by regulating each link of immunne response, the process of blocking-up disease reaches therapeutic purposes.What use clinically at present mainly is anti-inflammatory drug and immunosuppressive drug.
Autoimmune hepatitis is the chronic inflammatory disease of a kind of etiology unknown based on pathological changes around liver, the portal vein, has various autoantibodys in the peripheral blood simultaneously.Many research reports are arranged, and behind the viral infection, particularly hepatitis B virus infection can be induced the generation of this disease.It is relevant that the damage of its immunopathogenesis and autosensitization T cell are attacked, and is to be subjected to autoantigen to stimulate afterwards activated, conversion, propagation and differentiation to form by autoreactive T cell.Work as CD
+Be divided into cytotoxic T cell after the 4T cell is activated, directly cause tardy hypersensitivity inflammation and damage hepatocyte thereby discharge pro-inflammatory cytokine (as TNF α).
In organ transplantation, owing to be external foreign body for receptor from the transplant organ of donor, so the immune system of receptor is subjected to exciting the back to attack this foreign body, so that transplant organ is excluded as foreign body.The rejection phenomenon of organ transplantation that Here it is.In order to prevent rejection, the just essential immunity that suppresses receptor
At present, this area lacks effective immunosuppressant and the little medicine of side effect.For example, this area also lacks with the immunorepressive report of Chinese medicine composition, for example still do not report at present Caulis Sinomenii, the Radix Paeoniae Alba and work as the effect that the compositions that is grouped into has immunosuppressant and organ transplantation rejection, more do not have such composition of medicine to be used for the treatment of autoimmune disease.
In order to adapt to immunorepressive needs, this area presses for the medicine that medicine, the especially active component of developing new immunosuppressant (as be used for the treatment of autoimmune disease and suppress the organ transplant rejection) derive from Chinese crude drug.
Summary of the invention
Purpose of the present invention just provides a kind of medicine and/or dietary supplement that contains pure Chinese medicine extract, and it is immunosuppressant effectively, therefore can be used for treating autoimmune disease and suppresses the organ transplant rejection.
In a first aspect of the present invention, a kind of purposes of pharmaceutical composition is provided, by the gross weight of compositions, described compositions contains following active component:
Sinomenine 30-75mg/g;
Paeoniflorin 8-15mg/g;
Ferulic acid 1.5-3mg/g,
And pharmaceutically acceptable carrier,
Wherein, described compositions is used to prepare immunorepressive medicine.
In another preference, the content of sinomenine is 40-60mg/g in the described compositions, and paeoniflorin is 10-15mg/g.
In another preference, it is characterized in that described medicine is used for the treatment of autoimmune disease or is used to suppress the organ transplant rejection.
In addition, the also available medical material quantity of a kind of pharmaceutical composition of the present invention is limited.In other words, the present invention also provides a kind of purposes of pharmaceutical composition, and described compositions contains the necessary component that is selected from down group:
The Caulis Sinomenii of 45-85 parts by weight;
The Radix Paeoniae Alba of 8-20 parts by weight;
The Radix Angelicae Sinensis of 3-10 parts by weight;
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, and the pharmaceutically acceptable carrier of surplus,
Wherein, described compositions is used to prepare immunorepressive medicine.
In another preference, described pharmaceutical composition contains:
The Caulis Sinomenii of 55-85 parts by weight;
The Radix Paeoniae Alba of 10-20 parts by weight;
The Radix Angelicae Sinensis of 4-10 parts by weight,
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 50-99% of composition total weight.
In another preference, it is characterized in that it contains:
The Caulis Sinomenii of 60-85 parts by weight;
The Radix Paeoniae Alba of 12-15 parts by weight,
The Radix Angelicae Sinensis of 5-8 parts by weight.
In another preference, described medicine is used for the treatment of autoimmune disease or is used to suppress the organ transplant rejection.
In another preference, described pharmaceutical composition is tablet or capsule preparations.
In another preference, described pharmaceutical composition also contains the material that is selected from down group: ciclosporin, cyclophosphamide or azathioprine.
In a third aspect of the present invention, a kind of purposes of mixture is provided, described mixture is by the Caulis Sinomenii of 45-85 parts by weight; The Radix Paeoniae Alba of 8-20 parts by weight; Constitute with the Radix Angelicae Sinensis of 3-10 parts by weight, perhaps described mixture contains sinomenine 30-75mg/g; Paeoniflorin 8-15mg/g; With ferulic acid 1.5-3mg/g, wherein, described mixture is used to prepare immunorepressive medicine.
In another preference, described mixture is used for the medicine that preparation (a) suppresses autosensitization T cell proliferation; (b) suppress tardy super quick immunoreactive medicine; (c) medicine of inhibition TNF alpha levels; (d) medicine of treatment autoimmune disease; Or (e) medicine of anti-organ transplantation rejection.
In a fourth aspect of the present invention, the method for preparing pharmaceutical composition of the present invention or dietary supplement is provided, it comprises step:
(1). choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.1-0.5% sulphuric acid liquid, transfer pH=12 ± 0.5 with lime cream then, must precipitate, again with the 90-95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization is dissolved in this crystallization ebullient 60-70% (as 65%) ethanol at last and adds ammonia and transfers pH to 9 ± 0.2 then, can obtain purity and be the sinomenine greater than 95% (as 98%).
(2). obtain Radix Angelicae Sinensis and Radix Paeoniae Alba extractum with alcohol extracting method;
(3). Caulis Sinomenii extractum is fitted over Radix Angelicae Sinensis and Radix Paeoniae Alba extractum, and acquisition has the pharmaceutical composition of the active constituent of above-mentioned concentration,
Wherein the order of step (1) and (2) is interchangeable.
Preferably, used Caulis Sinomenii medical material is the higher Caulis Sinomenii coarse powder of sinomenine content.
The specific embodiment
The inventor is through extensive and deep research, be surprised to find that the compositions that Caulis Sinomenii, the Radix Paeoniae Alba and Radix Angelicae Sinensis three form by a certain percentage, have immunosuppressive action preferably thereby can be used for treating autoimmune disease and suppress rejection in the organ transplantation.Finished the present invention on this basis.
Can be used for compositions of the present invention, is a kind of with Caulis Sinomenii, the Radix Paeoniae Alba with when being classified as necessary component or corresponding effective ingredient (being sinomenine, white peony root's total glycoside and ferulic acid) is the compositions of neccessary composition.Compositions of the present invention can be pharmaceutical composition or dietary supplement.A kind of preferred compositions is disclosed in and is entitled as among the Chinese patent ZL01819981.X of " be used for the treatment of or improve arthritic pharmaceutical composition and dietary supplement ", and the document all is incorporated herein by reference.
As used herein, term " necessary component " refers to necessary Chinese medicine medical material, i.e. Caulis Sinomenii (Sinomemiumacutum), the Radix Paeoniae Alba (Paeomia lactiflora) and Radix Angelicae Sinensis (Angelica sinensis).
As used herein, term " neccessary composition " refers to the chemical substance as necessity of active component, promptly sinomenine (Sinomemine), white peony root's total glycoside (total glucosides ofpaecony, TGP) and ferulic acid (Ferolicacid).
As used herein, term " white peony root's total glycoside " and " paeoniflorin " are used interchangeably, and all refer to the portugal glycoside material in the Radix Paeoniae Alba.
As used herein, term " comprise " comprised " containing ", " basically by ... constitute " and " by ... formation ".
As used herein, term " basically by ... constitute " refer in compositions, except containing neccessary composition or necessary component, also can contain a spot of and not influence the submember and/or the impurity of effective ingredient.For example, can contain sweeting agent to improve taste, antioxidant in case oxidation, and other this areas additive commonly used.Usually Caulis Sinomenii (Sinomemium acutum), the Radix Paeoniae Alba (Paeomia lactiflora) and Radix Angelicae Sinensis (Angelica sinensis) account at least 70% of whole Chinese medicine medical material weight, and preferably at least 80%, more preferably at least 90%.
As used herein, term " pharmaceutically acceptable carrier " refers to be used for the treatment of the carrier of agent administration, comprises various excipient and diluent.This term refers to some medicament carriers like this: they itself are not necessary active component, and do not have undue toxicity after using.Suitable carriers is well known to those of ordinary skill in the art.(Mack Pub.Co. can find discussing fully about pharmaceutically acceptable excipient in N.J.1991) at Remington ' s Pharmaceutical Sciences.Acceptable carrier can contain liquid on combination of Chinese medicine is learned, as water, saline, glycerol and ethanol.In addition, also may there be complementary material in these carriers, as wetting agent or emulsifying agent, pH buffer substance etc.Come from Caulis Sinomenii, the Radix Paeoniae Alba, Radix Angelicae Sinensis remove neccessary composition (be sinomenine (Sinomemine), white peony root's total glycoside (Total glucosides ofpaecony, TGP) and ferulic acid (Ferolic acid).) outside inessential composition, and other inessential compositions (for example other complementary medical materials) are also included within the definition of pharmaceutically acceptable carrier.
As used herein, term " compositions of the present invention " comprises pharmaceutical composition and dietary supplement, as long as they contain or basically by (1) Caulis Sinomenii or sinomenine; (2) Radix Paeoniae Alba or white peony root's total glycoside; (3) Radix Angelicae Sinensis or ferulic acid constitute.Usually, the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, preferably 50-99%, more preferably 60-90%.
In addition, the present composition can contain the treatment autoimmune disease or suppress other materials of organ transplant rejection, ciclosporin for example, cyclophosphamide, azathioprine etc. or its combination.
In pharmaceutical composition of the present invention, be (1) Caulis Sinomenii (Sinomemium acutum) as three kinds of Chinese medicine medical materials of necessary component, active component wherein is sinomenine (Sinomemine); (2) Radix Paeoniae Alba (Paeomia lacttflora); Active component wherein be white peony root's total glycoside (Total glucosides of paecony, TGP); (3) Radix Angelicae Sinensis (Angelica sinensis), active component wherein are ferulic acid (Ferolic acid).
Medicine of the present invention is closely related to the content of the inhibition effect of immunity and necessary active component.Studies show that,, should make this active ingredient of drugs content reach certain scope in order to obtain stable immunosuppressant effect.The scope of the reasonable content of each active component is in the medicine:
Sinomenine 30-75mg/g, 40-60mg/g preferably,
Paeoniflorin 8-15mg/g, preferably, 10-15mg/g,
Ferulic acid 1.5-3mg/g.
Except limiting the compositions of the present invention by necessary active component, the proportioning of also available necessary component (medical material) limits compositions of the present invention.
In the present composition, by weight, the appropriate proportioning of three kinds of necessary medical materials is:
45-85 parts by weight, preferably 55-85 parts by weight, the more preferably Caulis Sinomenii of 60-85 parts by weight;
8-20 parts by weight, preferably 10-20 parts by weight, the more preferably Radix Paeoniae Alba of 12-15 parts by weight;
The 3-10 parts by weight, 4-10 parts by weight preferably, the Radix Angelicae Sinensis of 5-8 parts by weight more preferably,
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, preferably 50-99%, more preferably 60-95%.The material of surplus is pharmaceutically acceptable carrier, for example starch, maltodextrin etc.
In order to make preparation that good therapeutic effect be arranged, the effective active component content in the preparation is crucial.The inventor has also set up a cover and has detected in the said preparation high performance liquid chromatogram (HPLC) assay method of active component in each Chinese crude drug for this reason, monitors the various active component in raw material and the preparation.
Pharmaceutical composition of the present invention or dietary supplement can be made the dosage form of any routine by conventional method, preferably tablet or capsule preparations.
In another aspect of this invention, provide a kind of method for preparing pharmaceutical composition of the present invention or dietary supplement.
Conventional Chinese medicine extraction method is difficult to make the active component in the extract to reach the curative effect that higher concentration guarantees said preparation.The inventor finds that when using the Caulis Sinomenii immunosuppressant according to pharmacological research, adult's effective dose is preferably 40-80mg/ days, should contain sinomenine 40-60mg in every like this restraint agent, and this concentration is that general extracting method is unapproachable.A kind of effective ways that extract sinomenine have been tested for this reason.
In this extraction method, at first choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.1-0.5% sulphuric acid liquid, transfer PH=12 ± 0.5 with lime cream then, must precipitate, again with the 90-95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization is dissolved in this crystallization ebullient 60-70% (as 65%) ethanol at last and adds ammonia and transfers PH to 9 ± 0.2 then, can obtain purity and be the sinomenine greater than 95% (as 98%).
Use conventional alcohol extracting method simultaneously, obtain the extractum of the Radix Angelicae Sinensis and the Radix Paeoniae Alba.For example, Radix Angelicae Sinensis is refluxed with 70% ethanol water, then the solution that obtains is concentrated, thereby obtain Radix Angelicae Sinensis concentrate (as extractum).In addition, through spray do after, also can obtain Radix Angelicae Sinensis concentrate powder.Similarly, can obtain the extractum of the Radix Paeoniae Alba.Certainly, preferably, can obtain to contain simultaneously the concentrate (as extractum) of Radix Angelicae Sinensis and two kinds of active princlples of the Radix Paeoniae Alba.
At last,, more a certain proportion of these extractum are fitted over together, so just can reach the concentration that needs according to the needs of preparation.
In a preference, the method for preparing medicine of the present invention comprises step:
(1), makes purity for greater than 95% sinomenine with above-mentioned method for optimizing.
(2), obtain Radix Angelicae Sinensis and Radix Paeoniae Alba extractum with conventional alcohol extracting method.
(3), according to the preparation needs, again these two kinds of extractum and sinomenine are fitted over together, so just can reach the concentration that needs, wherein the order of step (1) and (2) is interchangeable.
The invention has the advantages that:
(1) component is simple, active component is clear and definite and with strong points;
(2) can quantitatively control active component, thereby ensure the quality of products;
(3) with low cost;
(4) inhibitory action to immunity is obvious.
Further set forth the present invention below in conjunction with embodiment.Should be understood that these embodiment only to be used to set forth the present invention and be not used in restriction the present invention.In an embodiment, percentage ratio is weight percentage, and umber is parts by weight, unless stated otherwise.
Embodiment 1
The preparation of pharmaceutical composition A
In this embodiment, provide a kind of pharmaceutical composition (compositions A), wherein, the proportioning of three kinds of Chinese medicines is:
Caulis Sinomenii 82 parts by weight (820 gram)
The Radix Paeoniae Alba 12 parts by weight (120 gram)
Radix Angelicae Sinensis 6 parts by weight (60 gram)
All through the HPLC test, quality meets the requirements three kinds of used in the present embodiment Chinese medicines.
At first choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.4% sulphuric acid liquid, transfer PH=12 with lime cream then, must precipitate, again with 95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization then is dissolved in this crystallization ebullient 65% ethanol at last and adds ammonia and transfers PH to 9, can obtain purity and be 98% sinomenine.
Take by weighing the Radix Angelicae Sinensis or the Radix Paeoniae Alba, add 70% alcohol reflux, the extracting solution concentrating under reduced pressure becomes the extractum shape, and 1 gram eumenol is equivalent to 1.6 gram crude drugs, and 1 gram Radix Paeoniae Alba extractum is equivalent to 4.4 gram crude drugs.
With sinomenine and Radix Angelicae Sinensis, the abundant mixing of Radix Paeoniae Alba alcohol-extracted extract, carried out vacuum drying (60～70 ℃) 3.5-4.0 hour, make dry extract, dry extract to be pulverized, 60 orders sieve, and incapsulate.In this embodiment, Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for about 80% of composition total weight.
Embodiment 2
The preparation of pharmaceutical composition B
Press the extracting method described in the embodiment 1, make sinomenine respectively, the Radix Paeoniae Alba and Radix Angelicae Sinensis are made concentrated extract.Each extract is behind assay, and according to the form below A prescription takes by weighing the back fully to be mixed with adjuvant (microcrystalline cellulose and magnesium stearate), and with encapsulating capsule behind the dry granulation, makes totally 1000 of capsule preparations, and the inclusions of every capsules is 300mg or 250mg.
Table A: every capsules contains various one-tenth dosis refractas
| Content (by crude drug) | Content (by active component) | |
| Caulis Sinomenii or sinomenine | 2g Caulis Sinomenii (80 weight portion) | 60mg sinomenine/g compositions |
| The Radix Paeoniae Alba or peonine | The 350mg Radix Paeoniae Alba (14 weight portion) | 11mg peoniflorin/g compositions |
| Radix Angelicae Sinensis or ferulic acid | 75mg Radix Angelicae Sinensis (3 weight portion) | 1.5mg ferulic acid/g compositions |
Embodiment 3
The immunosuppressive action of Caulis Sinomenii, the Radix Paeoniae Alba, Radix Angelicae Sinensis compound medicine
In present embodiment 1 respectively the Caulis Sinomenii of preparation in the test implementation example 2, the Radix Paeoniae Alba, Radix Angelicae Sinensis compound medicine to the inhibitory action of immunity.
1, to the influence of thymic weight
Thymus is the organ of T cell development differentiation, thus suppress the growth of thymus, also with the growth and the differentiation of suppressor T cell.Rat is got in experiment, and is divided into blank group, negative control group (the tripterygium glycosides sheet is available from ShangHai Fudan Fuhua Pharmaceutical Co., Ltd) and administration group at random.Animal is irritated stomach respectively and gives distilled water, variable concentrations tried thing or positive control drug.Every day 1 time, continuous 27 days.Get the half animal respectively, after the execution, cut open and get thymus, weigh, calculate organ index.The results are shown in Table 1.
Table 1, pharmaceutical composition are to the influence of rat chest gland weight
| Group | Dosage (mg/kg) | Number of animals | Thymus index * 10 on the 14th -2，g/10g | Thymus index * 10 on the 26th -2，g/10g |
| Blank | 20ml | 10 | 1.97 | 1.54 |
| The tripterygium glycosides sheet | 18mg | 10 | 1.82 | 1.58 |
| Pharmaceutical composition | 120mg 180mg 240mg | 10 10 10 | 1.91 1.72 1.60 | 1.43 1.71 1.46 |
Data show that pharmaceutical composition of the present invention can obviously reduce rat chest gland weight.This points out it can directly influence the propagation of autosensitization T cell, thereby can reduce autoimmune response.
2, to the tardy super quick immunoreactive influence of rat
With adjuvant arthritis rats is animal model.Because adjuvant-induced arthritis can cause tardy super quick immunoreation, can cause that rat causes scorching ankle joint offside joint swelling takes place.If medicine can suppress the swelling of offside, just mean that this medicine can suppress delayed hypersensitive reaction.
Rat is got in experiment, is divided into normal control group, blank group, positive controls and group medicine group at random.Each treated animal measures the volume of hind leg foot sole of the foot portion respectively except the normal control group, and every Mus surveys twice, averages as causing scorching preceding volume.What each treated animal irritated respectively that stomach gives distilled water, variable concentrations is tried thing or positive control drug.Every day 1 time is continuous 27 days.Each treated animal was subcutaneous in the right hind foot sole of the foot except that the normal control group on 1 in administration, and injection Freund ' s Freund's complete adjuvant 0.1ml/1 only.Survey right back sufficient sole of the foot volume respectively at causing scorching back, and survey on the the 20th, 23,26 is calculated inhibitory rate of intumesce to parapodum sole of the foot volume behind the Yu Zhiyan.Now that medicine is scorching in the expand table 2 that the results are shown in of suppression ratio of the swollen sole of the foot of parapodum to causing.
Table 2 pharmaceutical composition causes the influence of inflammation to the bloated suppression ratio (%) of the swollen sole of the foot of parapodum to rat
| Group | Dosage (mg/kg) | Number of animals (only) | Inhibitory rate of intumesce (the 26th day) |
| Blank | 20ml | 10 | |
| Tripterygium glycosides | 18 | 10 | 9.2 |
| Pharmaceutical composition | 120 180 240 | 10 10 10 | 20.3 41.4 37.2 |
Data show that pharmaceutical composition of the present invention can obviously suppress the bloated rate of the swollen sole of the foot of parapodum is promptly obviously suppressed tardy super quick immunoreation.Therefore the damage that can alleviate this reaction pair target tissue.
3, to the influence of TNF alpha levels in the rat blood serum
Cause tardy super quick immunoreactive immediate cause and be activated T lymphocytic emiocytosis pro-inflammatory cytokine (as TNF α etc.), also can alleviate damage target tissue so reduce TNF alpha levels in the serum.
Experimental technique is identical with " 2, to the tardy super quick immunoreactive influence of rat ", but adds the level of surveying TNF α in the serum.Mensuration is to cause scorching back the 14th, 27 day, getting the half animal respectively, after the anesthesia of 20% Ethylurethanm solution, extracts eyeball and gets blood, and centrifugal 5 minutes of 4000rpm gets determination of serum TNF alpha levels.The results are shown in Table 3.
Table 3 pharmaceutical composition causes the influence of scorching back 14 days serum TNF α to rat
| Group | Dosage (mg/kg) | Number of animals (only) | TNF α (OD value) |
| Blank | 20ml/kg | 10 | 0.070 |
| Tripterygium glycosides | 18 | 13 | 0.067 |
| Pharmaceutical composition | 120 180 240 | 10 10 10 | 0.068 0.064 0.062 |
Data show, pharmaceutical composition of the present invention can reduce and causes scorching back rat TNF alpha levels.Therefore also can reduce autoimmune response.
4, the antiinflammatory action of pharmaceutical composition
Another importance of treatment autoimmune disease is an antiinflammatory, so present embodiment has also been observed the antiinflammatory action that the pharmaceutical composition on Carrageenan causes scorching rat.
Experiment 2-3 month male rat, random packet comprises model group, administration group (3 dosage) and positive control drug group.Earlier the carrageenin in rat one rear flank limb foot subcutaneous injection 1% concentration causes inflammation, then respectively at cause scorching before and cause scorching back and measured the foot solvent in 2,5 hours.And calculate inhibitory rate of intumesce with this.
The results are shown in Table 4.
Table 4 pharmaceutical composition on Carrageenan causes the influence of scorching rat inhibitory rate of intumesce (%)
| Group | Dosage (mg/kg) | Number of animals (only) | Suppression ratio (%) 2 hours 5 hours |
| Blank | 20ml/kg | 12 | |
| Tripterygium glycosides | 18 | 12 | 59.68 42.94 |
| Pharmaceutical composition | 60 120 180 | 12 12 12 | 45.55 29.20 57.74 29.08 90.12 91.84 |
Data show that this pharmaceutical composition has tangible antiinflammatory action.Show that from above-listed all data it will be the good medicine and the auxiliary therapeutical agent of treatment autoimmune hepatitis that the existing immunosuppressive action of this pharmaceutical composition has antiinflammatory action preferably again.Also can be used for other and autoimmune response diseases associated such as chronic nephritis.
Embodiment 4
Caulis Sinomenii, the Radix Paeoniae Alba, Radix Angelicae Sinensis compound medicine are to the inhibitory action of organ transplantation rejection
Rejection in the organ transplantation has certain similar aspect immunology, whether also can be used for suppressing rejection in the organ transplantation in order to understand this pharmaceutical composition, tested the immunologic rejection effect that this pharmaceutical composition (Caulis Sinomenii, the Radix Paeoniae Alba, the Radix Angelicae Sinensis compound medicine of preparation among the embodiment 2) is transplanted the Mice Auricle cardiac muscle at present embodiment, to determine the inhibitory action of pharmaceutical composition of the present invention to the organ transplantation rejection.
Experiment is carried out with mice, at first gets newborn 24 hours rat hearts under aseptic condition, and this is cut in half as donor, plants in the Kunming mouse auricle subcutaneously then, and with the electrocardiogram monitoring electrocardio-activity, electrocardio disappears and takes place for rejection.
The results are shown in Table 5.
Table 5 medicine is to the inhibitory action of organ transplantation rejection
| Pharmaceutical composition dosage (mg/kg) | Number of animals (only) | Time-to-live (my god) |
| 0 | 12 | 8.1±2.0 |
| 60 | 12 | 10.2±1.5 |
| 120 | 11 | 11.4±2.1 |
| 180 | 12 | 12.3±1.2 |
Data show that pharmaceutical composition of the present invention can obviously prolong the time-to-live of transplanting cardiac muscle, and host-vs-graft reaction is had certain inhibitory action.In anti-organ transplantation rejection, potential clinical value is arranged.
Embodiment 5
The relation of necessary component or active component content and therapeutic effect
In this embodiment, analyzed the content and the treatment autoimmune disease of each medical material in the pharmaceutical composition of the present invention or its active component and suppress relation between the effect of organ transplant rejection effect aspect.
By being similar to embodiment 1 described method, be prepared as follows the compositions of proportioning, wherein the content of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis total amount and excipient is the percentage ratio that accounts for composition total weight.And test its influence to thymic weight by embodiment 3 described methods.
| Composition no | Caulis Sinomenii (parts by weight) | The Radix Paeoniae Alba (parts by weight) | Radix Angelicae Sinensis (parts by weight) | Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis total amount (wt%) | Excipient (wt%) |
| 1 | 50 | 15 | 7 | 50 | 50% starch |
| 2 | 60 | 12 | 6 | 60 | 20% starch+maltodextrin |
| 3 | 70 | 10 | 5 | 70 | 30% maltodextrin |
| 4 | 80 | 20 | 10 | 80 | 20% starch |
The result shows that compared with the control, these compositionss all can reduce thymic weight, but points out also immunosuppressant of these compositionss.
Compositions A among compositions 1-4 and the embodiment 1 and the compositions B among the embodiment 2 measure through high performance liquid chromatogram (HPLC), and the content of sinomenine is 30-75mg/g; Content of paeoniflorin is 8-15mg/g; Ferulaic acid content is 1.5-3mg/g.
Embodiment 6
The preparation of dietary supplement
By the method that is similar to embodiment 1, the preparation dietary supplement, wherein, the proportioning of three kinds of Chinese medicines is:
Caulis Sinomenii 60 parts by weight (600 gram)
The Radix Paeoniae Alba 10 parts by weight (100 gram)
Radix Angelicae Sinensis 5 parts by weight (50 gram)
The dry extract that makes is pulverized, and 60 orders sieve, and incapsulate.In this embodiment, Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for about 70% of composition total weight.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. the purposes of a pharmaceutical composition, by the gross weight of compositions, described compositions contains following active component:
Sinomenine 30-75mg/g;
Paeoniflorin 8-15mg/g;
Ferulic acid 1.5-3mg/g;
And pharmaceutically acceptable carrier,
It is characterized in that described compositions is used to prepare immunorepressive medicine.
2. purposes as claimed in claim 1 is characterized in that, the content of sinomenine is 40-60mg/g in the described compositions, and paeoniflorin is 10-15mg/g.
3. purposes as claimed in claim 1 is characterized in that, described medicine is used for the treatment of autoimmune disease or is used to suppress the organ transplant rejection.
4. the purposes of a pharmaceutical composition, described compositions contain the necessary component that is selected from down group:
The Caulis Sinomenii of 45-85 parts by weight;
The Radix Paeoniae Alba of 8-20 parts by weight;
The Radix Angelicae Sinensis of 3-10 parts by weight;
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, and the pharmaceutically acceptable carrier of surplus,
It is characterized in that described compositions is used to prepare immunorepressive medicine.
5. purposes as claimed in claim 4 is characterized in that, described pharmaceutical composition contains:
The Caulis Sinomenii of 55-85 parts by weight;
The Radix Paeoniae Alba of 10-20 parts by weight;
The Radix Angelicae Sinensis of 4-10 parts by weight,
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 50-99% of composition total weight.
6. purposes as claimed in claim 4 is characterized in that it contains
The Caulis Sinomenii of 60-85 parts by weight;
The Radix Paeoniae Alba of 12-15 parts by weight,
The Radix Angelicae Sinensis of 5-8 parts by weight.
7. purposes as claimed in claim 4 is characterized in that, described medicine is used for the treatment of autoimmune disease or is used to suppress the organ transplant rejection.
8. purposes as claimed in claim 4 is characterized in that, described pharmaceutical composition also contains the material that is selected from down group: ciclosporin, cyclophosphamide or azathioprine.
9. the purposes of a mixture, described mixture is by the Caulis Sinomenii of 45-85 parts by weight; The Radix Paeoniae Alba of 8-20 parts by weight; Constitute with the Radix Angelicae Sinensis of 3-10 parts by weight, perhaps described mixture contains sinomenine 30-75mg/g; Paeoniflorin 8-15mg/g; With ferulic acid 1.5-3mg/g, it is characterized in that described mixture is used to prepare immunorepressive medicine.
10. purposes as claimed in claim 9 is characterized in that, described mixture is used for the medicine that preparation (a) suppresses autosensitization T cell proliferation; (b) suppress tardy super quick immunoreactive medicine; (c) medicine of inhibition TNF alpha levels; (d) medicine of treatment autoimmune disease; Or (e) medicine of anti-organ transplantation rejection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101346031A CN100548308C (en) | 2005-12-16 | 2005-12-16 | The pharmaceutical composition that is used for autoimmune disease and organ transplantation rejection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101346031A CN100548308C (en) | 2005-12-16 | 2005-12-16 | The pharmaceutical composition that is used for autoimmune disease and organ transplantation rejection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1981778A true CN1981778A (en) | 2007-06-20 |
| CN100548308C CN100548308C (en) | 2009-10-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2005101346031A Expired - Fee Related CN100548308C (en) | 2005-12-16 | 2005-12-16 | The pharmaceutical composition that is used for autoimmune disease and organ transplantation rejection |
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| Country | Link |
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| CN (1) | CN100548308C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105031555A (en) * | 2015-09-17 | 2015-11-11 | 天津医科大学 | Compound Chinese traditional medicine preparation for inducing immune tolerance and preparing method and application thereof |
| CN107582583A (en) * | 2017-10-30 | 2018-01-16 | 无锡福祈制药有限公司 | The compound preparation of rejection after a kind for the treatment of organs transplanting |
-
2005
- 2005-12-16 CN CNB2005101346031A patent/CN100548308C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105031555A (en) * | 2015-09-17 | 2015-11-11 | 天津医科大学 | Compound Chinese traditional medicine preparation for inducing immune tolerance and preparing method and application thereof |
| CN105031555B (en) * | 2015-09-17 | 2018-11-27 | 天津医科大学 | A kind of compound Chinese medicinal preparation of inducing immune tolerance and its preparation method and application |
| CN107582583A (en) * | 2017-10-30 | 2018-01-16 | 无锡福祈制药有限公司 | The compound preparation of rejection after a kind for the treatment of organs transplanting |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100548308C (en) | 2009-10-14 |
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