CN1179306A - Medicine containing tripdiolide for preventing and treating graft acute rejection - Google Patents
Medicine containing tripdiolide for preventing and treating graft acute rejection Download PDFInfo
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- CN1179306A CN1179306A CN 96117128 CN96117128A CN1179306A CN 1179306 A CN1179306 A CN 1179306A CN 96117128 CN96117128 CN 96117128 CN 96117128 A CN96117128 A CN 96117128A CN 1179306 A CN1179306 A CN 1179306A
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- radix tripterygii
- tripterygii wilfordii
- wilfordii lactone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
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Abstract
A medicine for preventing acute rejection reaction of grafted organ contains Tripterygium wilfordii lactonol. If its dosage is 120-180 micrograms/kg/day, it has a distinct effect of elongating the survival period of grafted organ. It can be applied in conjunction with cyclsoporamycin A or along with cyclosporamycin A, azathioprine and corticoid for higher curative effect.
Description
The present invention relates to the medicine of the control graft acute rejection of epoxy diterpene-kind compound.
Radix Tripterygii Wilfordii also once was used for the treatment of arthritis and dermatosis as medical herbs at folklore for a long time.Clinical and experimentatioies a large amount of since the seventies show that Radix Tripterygii Wilfordii has pharmacological actions such as antiinflammatory, immunosuppressant and antifertility.
What the rejection of control graft acute was used at present is that Ciclosporin A, azathioprine and 17-hydroxy-11-dehydrocorticosterone are three main anti-rejection medications.
The objective of the invention is with Radix Tripterygii Wilfordii lactone alcohol as control graft acute rejection medicine.
Radix Tripterygii Wilfordii lactone alcohol claims triptolide again, is colourless acicular crystal, and its fusing point is 227-228 ℃.Following structure is arranged:
According to inventor's research, Radix Tripterygii Wilfordii lactone alcohol significantly has the curative effect of the time-to-live that prolongs allograft, can be as the medicine of control graft acute rejection.
Research according to the inventor, adopt Balb/c (H.2b) mice to make donor, C57BL/6 (H-2d) mice makes receptor, carry out allogeneic skin graft under the aseptic condition, experimental results show that, dosage is the existing tangible immunologic rejection effect of the Radix Tripterygii Wilfordii lactone alcohol of 200 μ m/kg/ days, the time-to-live of skin graft similar to the curative effect of the Ciclosporin A of 20mg/kg/ day (seeing embodiment 1).
Adopt Balb/c (H-2b) mice to make donor, C57BL (H-2d) mice makes receptor, and aseptic condition is implemented the allogeneic Establishing Mice Heart Heterotopic Transplantation down, experiment showed, that dosage is that the Radix Tripterygii Wilfordii lactone alcohols of 200 μ m/kg/ days also has tangible immunologic rejection effect.(seeing embodiment 2).
Adopt inbreeding Lou rat to make donor, inbred line Wistar-Fister rat makes receptor, aseptic condition is implemented allogeneic rat ectopic kidney down and is transplanted, and experiment showed, that dosage is the also existing tangible immunologic rejection effects (seeing embodiment 3) of 200 μ m/kg/ day Radix Tripterygii Wilfordii lactone alcohols.
Radix Tripterygii Wilfordii lactone alcohol can with the Ciclosporin A Synergistic treatment, low dose of Radix Tripterygii Wilfordii lactone alcohol adds low dose of Ciclosporin A and is notable therapeutic effect, the time-to-live of its skin plant prolongs than matched group (sees embodiment 1,3) more than one times.
Clinical research according to the inventor, with at present both at home and abroad commonly used with Ciclosporin A, azathioprine is that three main immunologic rejection therapies are compared with 17-hydroxy-11-dehydrocorticosterone, the application of Radix Tripterygii Wilfordii lactone alcohol can reduce the incidence rate of allogeneic cadaveric renal transplantation postoperative acute cell rejection significantly, postpone the time that the postoperative acute rejection takes place, improve the survival rate in 1 year of allogeneic cadaveric renal transplantation postoperative (seeing embodiment 4) significantly.
According to inventor's research, operation medication on the same day does not almost have any preventive and therapeutic effect, and along with shifting to an earlier date of administration time, the time-to-live of graft correspondingly prolongs.The preventive and therapeutic effect of art administration in preceding 14 days is significantly better than operation preceding 3 days and administration in 7 days.
With containing the medicine of Radix Tripterygii Wilfordii lactone alcohol tangible curative effect is arranged as the rejection of control graft acute, particularly the approach of the immunologic rejection effect of Radix Tripterygii Wilfordii lactone alcohol is different from Ciclosporin A fully, because when two kinds of drug doses are little when not having obvious immunologic rejection curative effect, unite use then the mutual synergism by between the two can produce significant curative effect.
Embodiment 1.
The experimental verification Radix Tripterygii Wilfordii lactone alcohol has the curative effect of the time-to-live that prolongs allograft
Animal: donor is selected Balb/c (H-2b) mice for use; Receptor is selected C57BL/6 (H-2d) mice for use.Male and female are regardless of.Allogeneic skin graft art under the aseptic condition
Experimental drug:
Medicine source concentration dilution liquid
Triptolide China medical courses in general institute skin grinds the 0.03mg/ml of institute 1% Tween 80
CsA Sandoz Ltd 3mg/ml 1% Tween 80
Contrast liquid 1% Tween 80 administering mode: per os gavages the amount-result relation of 0.5ml/10g/ time 1.1 Radix Tripterygii Wilfordii lactone alcohol control allogenic skin graft acute rejection curative effect:
The Balb/c mice is divided into 3 groups, i.e. experiment contrast group (n-8); Radix Tripterygii Wilfordii lactone alcohol treatment group (n=18) and CsA treatment group (n=17).Each treatment group is all in skin transplantation medication in preceding 14 days, and by different dosages be further divided into height, in low three treatment groups, wherein Radix Tripterygii Wilfordii lactone alcohol dosage be 200,100,50ug/kg/ day, CsA is 20,10,5mg/kg/ day.Experimental result sees Table 1, and the average transplanting skin graft time-to-live of matched group Balb/c mice is 9.8 ± 0.4.Radix Tripterygii Wilfordii lactone alcohol treatment group is transplanted the mean survival time of skin graft, is followed successively by 10.6 ± 0.5 by low dosage to high dose, 13.8 ± 0.4 and 17.2 ± 0.4 days.The mean survival time of CsA treatment group is 11.7 ± 0.53,13.7 ± 0.5 and 20.5 ± 0.5 days.The amount-result relation group example number time-to-live mean survival time of table 1. Radix Tripterygii Wilfordii lactone alcohol control allogenic skin graft acute rejection curative effect
Matched group 69 everyday, 10,10,10,10,10 9.8 ± 0.4 Radix Tripterygii Wilfordii lactone alcohol treatment group
50ug/Kg/day 5 10，10，11，11，11 10.6±0.5
100ug/Kg/day 6 13，14，14，14，14，14 13.8±0.4
200ug/Kg/day 5 17,17,17,17,18 17.2 ± 0.4CsA treatment groups
5mg/Kg/day 6 11，11，12，12，12，12 11.7±0.5
10mg/Kg/day 6 13，13，14，14，14，14 13.7±0.5
20mg/Kg/day 6 20，20，21，21，21，21 20.5±0.5
Therefore, Radix Tripterygii Wilfordii lactone alcohol has the effect of anti-graft acute rejection, and its effect is closely related with the dosage of medication.The Radix Tripterygii Wilfordii lactone alcohol of 200ug/kg/day has tangible immunologic rejection effect, and the time-to-live of skin graft is similar to the curative effect of the CsA of 20mg/kg/day.1.2 the time-effect relationship of Radix Tripterygii Wilfordii lactone alcohol control allogenic skin graft acute rejection curative effect:
The treatment group is 28,14,7,3 days before skin transplantation and operation medication on the same day respectively, and dosage is 200ug/kg/ day.Experimental result sees Table 2.Operation medication on the same day does not almost have any control, and effect is along with administration time shifts to an earlier date, and the time-to-live of its time graft also correspondingly prolongs.The preventive and therapeutic effect of art administration in preceding 14 days is significantly better than the animal of preceding 3 days of art and medication in 7 days.Although the time-to-live that art administration in preceding 28 days can further improve graft was compared with art in preceding 14 days, there is no obvious superiority.The time-effect relationship group of table 2. Radix Tripterygii Wilfordii lactone alcohol control allogenic skin graft acute rejection curative effect shifts to an earlier date medication sky numerical example and counts the time-to-live mean survival time
It is matched group 69 everyday, 10,10,10,10,10 9.8 ± 0.4 Radix Tripterygii Wilfordii lactone alcohol treatment groups
0 6 10，10，10，11，11，11 10.6±0.5
-3 6 12，12，12，12，13，13 12.8±0.8
-7 6 13，14，14，14，14，14 13.8±0.4
-14 5 17，17，17，17，18 17.2±0.4
-28 6 17,17,18,18,19, the synergism of 19 18.0 ± 0.51.3 Radix Tripterygii Wilfordii lactone alcohol and CsA:
The Balb/c mice is divided into experiment contrast group (n=8); Low dose of Radix Tripterygii Wilfordii lactone alcohol treatment group (n=6); Low dose of CsA treatment group (n=6) and medicine Synergistic treatment group (n=6).The treatment group is all given Radix Tripterygii Wilfordii lactone alcohol 50ug/kg/ day respectively in skin transplantation medication in preceding 14 days; Or CsA5mg/kg/ day; Or triptolide alcohol 50ug/kg/ day and CsA5mg/kg/ day, experimental result sees Table 3.Medicine Synergistic treatment group as seen from table, promptly low dose of Radix Tripterygii Wilfordii lactone alcohol adds low dose of CsA treatment group treatment group and presents notable therapeutic effect, and the time-to-live of its graft contrasts and prolongs more than one times.The synergistic comparison of table 3. Radix Tripterygii Wilfordii lactone alcohol and CsA
Group shifts to an earlier date medication sky numerical example and counts the time-to-live mean survival time
It everyday
Matched group
6 9，10，10，10，10，10 9.8±0.4
Low dose of Radix Tripterygii Wilfordii lactone alcohol treatment group
50ug/Kg/day -14 5 10，10，11，11，11 10.6±0.5
Low dose of CsA treatment group
5mg/Kg/day -14 6 11，11，12，12，12，12 11.7±0.5
Medicine Synergistic treatment group
CsA+Triptolide -14 6 19，21，21，25，25，26 22.9±2.9
0 6 13，13，16，16，16，17 15.2±1.7
Therefore, the approach of this research prompting Radix Tripterygii Wilfordii and CsA rejection effect is incomplete same.Therefore, when two kinds of medication combined uses of no obvious immunologic rejection curative effect, the mutual synergism by between the two can produce significant curative effect.
The curative effect of embodiment 2. Radix Tripterygii Wilfordii lactone alcohols control allogeneic heart transplantation acute rejection
Animal: donor is Balb/c (H-2b) mice, and receptor is C57BL/6H-2d) mice.Aseptic condition is implemented the allogeneic Establishing Mice Heart Heterotopic Transplantation down.
The experiment grouping: animal is divided into Radix Tripterygii Wilfordii lactone alcohol treatment group, A treatment of ring bag mycin and experiment contrast.Wherein Radix Tripterygii Wilfordii lactone alcohol treatment group is distinguished administration 50ug/kg/day (n=6) and 200ug/kg/day (n=6); It is 5mg/kg/day (n=6) and 20mg/kg/day (n=6) that medication is respectively organized in the Ciclosporin A treatment.Matched group (n=6) is only given 1% Tween 80 solution of equivalent.Table 4. Radix Tripterygii Wilfordii lactone alcohol prolongs the time-to-live of heterotopic transplantation heart of the same race.
Group example number time-to-live mean survival time
Everyday
Radix Tripterygii Wilfordii lactone alcohol treatment group
200ug/Kg/day 5 11，11，14，14，14 12.8±1.6
Ciclosporin A treatment group
20mg/Kg/day 4 15，17，18，19，19， 17.6±1.7
Transplant heart matched group
65,6,7,7,8, the curative effect of 8 6.8 ± 1.23. experimental verification Radix Tripterygii Wilfordii lactone alcohol control allograft renal transplantation acute rejection
Animal: donor is selected inbred line Lou rat for use, and receptor is selected inbred line Wistar-Fister rat for use.Aseptic condition is implemented different rat ectopic kidney transplantation of the same race down.
The experiment grouping: animal is divided into Radix Tripterygii Wilfordii lactone alcohol treatment group, Ciclosporin A treatment group, therapeutic alliance group, experiment contrast group and sham operated rats.Wherein Radix Tripterygii Wilfordii lactone alcohol treatment group is given Radix Tripterygii Wilfordii lactone alcohol 50ug/kg/day (n=12), 100ug/kg/day (n=10), and 200ug/kg/day (n=12) respectively; Ciclosporin A treatment group is given Ciclosporin A 5mg/kg/day (n=10), 10mg/kg/day (n=11) and 20mg/kg/day (n=12) respectively.The therapeutic alliance group then gives Ciclosporin A and the 50ug/kg/day Radix Tripterygii Wilfordii lactone alcohol (n=12) of 5mg/kg/day simultaneously.Matched group (n=12) and sham operated rats (n=6) are only given 1% Tween 80 solution of equivalent.Experimental result sees Table 5,6,7.The survival rate of table 5 Radix Tripterygii Wilfordii lactone alcohol treatment group rat treatment group rat implantation kidney
Time (my god) average time (my god)
Transplanted kidney matched group 48,8,9,10 11.7
Radix Tripterygii Wilfordii lactone alcohol treatment group
100ug/Kg/day 3 12，13，15 13.3
Ciclosporin A treatment group
20mg/Kg/day 3 24, the variation (cm) of 26,27 25.6 table 6 Radix Tripterygii Wilfordii lactone alcohol treatment group postoperatives 7 days and 14 days transplanted kidney major diameters and minor axis
7 days 14 days
Major diameter minor axis major diameter minor axis
Sham operated rats 0.67 ± 0.23 0.45 ± 0.17 0.89 ± 0.34 0.54 ± 0.23
n＝3 n＝3
Transplanted kidney matched group 9.03 ± 0.78 6.33 ± 0.54 12.67 ± 1.12 5.72 ± 1.01
N=4 n=3 Radix Tripterygii Wilfordii lactone alcohol treatment group
50ug/Kg/day 2.63±0.62 2.05±0.38 3.41±0.29 3.11±0.67
n＝4 n＝3
100ug/Kg/day 2.83±0.39 2.33±0.57 4.00±0.52 2.93±0.47
n＝4 n＝5
200ug/Kg/day 3.72±0.61 3.01±0.36 5.17±0.85 3.49±0.45
n＝3 n＝4
Ciclosporin A treatment group
5mg/Kg/day 2.84±0.57 2.11±0.41 3.63±0.54 2.96±0.60
n＝4 n＝4
10mg/Kg/day 3.17±0.29 2.83±0.34 5.28±0.59 3.42±0.35
n＝5 n＝3
20mg/Kg/day 5.33±0.74 3.87±0.67 5.15±0.45 4.65±0.26
N=4 n=5 pathological examination results: behind the renal transplantation the 7th day be massive inflammatory cells infiltrated in the nephridial tissue of visible matched group transplanted kidney, acute cellularitys such as interstitial edema and tubule inflammation are carried different reaction pathological change; Postoperative the 7th and 14 days, the transplanted kidney of 200ug/kg/day Radix Tripterygii Wilfordii lactone alcohol treatment group is organized only slight inflammatory cell infiltration, the scorching pathological changes of no tubule; Inflammatory cell infiltration and the scorching pathological changes of tubule that moderate is arranged in the transplanted kidney tissue of 100ug/kg/day Radix Tripterygii Wilfordii lactone alcohol treatment group; Pathological change in the transplanted kidney tissue of 50ug/kg/day Radix Tripterygii Wilfordii lactone alcohol treatment group is similar to matched group.The transplanted kidney of 20mg/kg/day Ciclosporin A treatment group is organized also rarely seen slight inflammatory cell infiltration, the inflammatory cell infiltration of visible moderate in the transplanted kidney tissue of 10mg/kg/day Ciclosporin A treatment group, acute cellularity rejection pathological changes such as interstitial edema and tubule inflammation; 5mg/kg/day Ciclosporin A treatment and the pathological change of transplanted kidney tissue similar to matched group.The variation (cm) of table 7 Radix Tripterygii Wilfordii lactone alcohol and Ciclosporin A therapeutic alliance group postoperative 7 days and 14 days transplanted kidney major diameters and minor axis
7 days 14 days
Major diameter minor axis major diameter minor axis
Sham operated rats 0.67 ± 0.23 0.45 ± 0.17 0.89 ± 0.34 0.54 ± 0.23
n＝3 n＝3
Transplanted kidney matched group 9.03 ± 0.78 6.33 ± 0.54 12.67 ± 1.12 5.72 ± 1.01
n＝4 n＝3
The therapeutic alliance group:
Ciclosporin A 5mg/Kg/day+ Radix Tripterygii Wilfordii lactone alcohol 50ug/Kg/day
3.67±0.46 2.83±0.29 4.78±0.41 3.13±0.75
n＝5 n＝4
Ciclosporin A 5mg/Kg/day+ Radix Tripterygii Wilfordii lactone alcohol 100ug/Kg/day
2.67±0.27 2.17±0.46 3.48±0.31 2.18±0.29
N=4 n=3 pathological examination results: with the contrast and compare, though 5mg/kg/day Ciclosporin A+50ug/kg/day Radix Tripterygii Wilfordii ester alcohol therapeutic alliance group rat, transplanted kidney is organized the inflammatory cell infiltration and the scorching pathological changes of a spot of tubule of visible moderate; 5mg/kg/day Ciclosporin A+100ug/kg/day Radix Tripterygii Wilfordii ester alcohol therapeutic alliance group rat, transplanted kidney is organized slight inflammatory cell infiltration and the scorching pathological changes of tubule; But the pathological change in its transplanted kidney tissue far is lighter than the transplanted kidney histo pathological change of matched group.Embodiment 4.
83 of patients that select this institute to implement renal transplantation the same period, male 71 people wherein, women 12 people; Whether accept the Radix Tripterygii Wilfordii lactone alcohol treatment by art above-mentioned patient is divided into two groups, first winding is subjected to Ciclosporin A, and azathioprine and 17-hydroxy-11-dehydrocorticosterone are three main immunologic rejection therapies, totally 22; Add before second group of art with totally 61 of Radix Tripterygii Wilfordii lactone alcohol treatments.Dosage is: Ciclosporin A 8mg/kg/ day, azathioprine 50mg/kg/ day, strong loose imperial 40mg/kg/ day of methyl, plain 120ug/kg/ day of wilforlide A.Two groups of patient's art acute rejections are sent out relatively seeing the following form of rate:
First group second group
Example time incidence rate example time incidence rate
Number % counted behind the % renal transplantation in 30 days:
Transplanted kidney function normal 13 59.1 56 91.8
The super rejection 1 4.6 00 of transplanted kidney
The critical change 2 9.1 5 8.2 of transplanted kidney
Transplanted kidney acute renal allograft rejection 6 27.3 00
Behind subtotal 22 61 renal transplantations in 120 days
Transplanted kidney function normal 15 75 37 91.2
The critical change 2 10 4 9.8 of transplanted kidney
Transplanted kidney acute renal allograft rejection 3 15 00
Subtotal 20 41 renal transplantations after 120 days to postoperative 1 year
Transplanted kidney function normal 14 70 26 92.9
The critical change 151 3.5 of transplanted kidney
Transplanted kidney acute renal allograft rejection 5 25 1 3.5
Subtotal 20 28
Claims (5)
1. a control graft acute rejection medicine is characterized in that containing Radix Tripterygii Wilfordii lactone alcohol.
2. control graft acute rejection medicine according to claim 1 is characterized in that dosage is 120-180 μ g/kg/ day.
3. control graft acute rejection medicine according to claim 1 is characterized in that the collaborative use of Radix Tripterygii Wilfordii lactone alcohol and Ciclosporin A.
4. control graft acute rejection medicine according to claim 1 is characterized in that Radix Tripterygii Wilfordii lactone alcohol and Ciclosporin A, azathioprine and 17-hydroxy-11-dehydrocorticosterone are used.
5. according to claim 1,3 or 4 described control graft acute rejection medicines, it is characterized in that beginning medication before operation, the preferred time is that art began medication in preceding 10-16 days.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96117128 CN1179306A (en) | 1996-10-15 | 1996-10-15 | Medicine containing tripdiolide for preventing and treating graft acute rejection |
| PCT/CN1997/000100 WO1998016219A1 (en) | 1996-10-15 | 1997-10-10 | The medicine containing triptolide for preventing and/or treating acute graft rejection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96117128 CN1179306A (en) | 1996-10-15 | 1996-10-15 | Medicine containing tripdiolide for preventing and treating graft acute rejection |
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| Publication Number | Publication Date |
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| CN1179306A true CN1179306A (en) | 1998-04-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96117128 Pending CN1179306A (en) | 1996-10-15 | 1996-10-15 | Medicine containing tripdiolide for preventing and treating graft acute rejection |
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| Country | Link |
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| CN (1) | CN1179306A (en) |
| WO (1) | WO1998016219A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100398544C (en) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | Aqueous triptolide alcohol derivative with high immunesuppressive activity and its application |
| CN106890187A (en) * | 2017-02-22 | 2017-06-27 | 中山大学附属第三医院 | Triptolide and its trim are suppressing the application during B cell produces antibody |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3631795A (en) * | 1994-09-15 | 1996-03-29 | Pharmagenesis, Inc. | Composition and method for immunotherapy |
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1996
- 1996-10-15 CN CN 96117128 patent/CN1179306A/en active Pending
-
1997
- 1997-10-10 WO PCT/CN1997/000100 patent/WO1998016219A1/en active Application Filing
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100398544C (en) * | 2002-09-18 | 2008-07-02 | 成都达远药物有限公司 | Aqueous triptolide alcohol derivative with high immunesuppressive activity and its application |
| CN106890187A (en) * | 2017-02-22 | 2017-06-27 | 中山大学附属第三医院 | Triptolide and its trim are suppressing the application during B cell produces antibody |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998016219A1 (en) | 1998-04-23 |
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