CN1116036C - Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases - Google Patents
Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases Download PDFInfo
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- CN1116036C CN1116036C CN 99103346 CN99103346A CN1116036C CN 1116036 C CN1116036 C CN 1116036C CN 99103346 CN99103346 CN 99103346 CN 99103346 A CN99103346 A CN 99103346A CN 1116036 C CN1116036 C CN 1116036C
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- pharmaceutical composition
- lupus erythematosus
- dihydroarteannuin
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Abstract
The present invention relates to a medical composition containing dihydroartemisinin. Pharmacodynamical, toxicological and clinical research indicates that the medical composition of the present invention is effective medicine for treating lupus erythematosus and photosensitive diseases. The medical composition can be made into various common preparations for clinical application, and has the characteristics of high efficiency, safety and no toxic effect and side effect.
Description
The present invention relates to a kind of medicine that is used for the treatment of lupus erythematosus and photosensitive diseases, especially for the pharmaceutical composition that contains dihydroarteannuin of treatment lupus erythematosus and photosensitive diseases.
Lupus erythematosus and polymorphous light eruption etc. are photosensitive diseases, and lupus erythematosus belongs to immune disease, serious harm health, particularly systemic lupus erythematosus (sle) are often invaded multiple organs such as connective tissue, blood vessel, internal organs, skin and with the systemic disease of crucial immunological abnormality.Modern medicine thinks that autoimmune disease is by the body's immunity disorder, cause the B cell function hyperfunction and produce a large amount of autoantibody, cause that immune complex calm (the lupus kidney often is lethal reason) in basement membrane in the tissue, particularly glomerule causes the III allergic reaction type.
The lupus erythematosus sickness rate has the trend of continuous rising in recent years, and to New York and San Francisco census of population, prevalence is respectively 13.4/10 ten thousand and 50.8/10 ten thousand according to U.S. Siegel and Fessel.Domestic Shanghai textile department census of population prevalence is that 70.4/10 ten thousand (women then is 113.3/10 ten thousand) are so the epidemiology of relevant primary disease and therapeutics research are subjected to domestic and international attention day by day.For the treatment of this disease, doctor trained in Western medicine is used heavy dose of corticosteroid hormone and immunosuppressant treatment more, and to the part patient may command state of an illness, but long-term prescription then causes serious toxic and side effects and complication, even becomes the lethal main cause of primary disease.The traditional Chinese medical science adopts the policy of determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, has developed the medicine of some therapy system lupus erythematosus in recent years.For example Chinese patent application 91103109 discloses a kind of pharmaceutical composition of therapy system lupus erythematosus, wherein contains 34 kinds of Chinese medicines; Chinese patent application 94103378 discloses a kind of pharmaceutical composition of therapy system lupus erythematosus, wherein contains ten plurality of Chinese.Above-mentioned these Chinese medicine compositions all are prescription drugss generally, generally all need the doctor according to patient's practical situation the composition of pharmaceutical composition to be accepted or rejected during use.Although Chinese patent medicine is also arranged, because its composition is many, preparation is complicated, also is not very convenient in actual use therefore.Dihydroarteannuin is the reducing compound of arteannuin, and its structural formula is as follows:
China begins from the seventies, and arteannuin has been carried out research extensively and profoundly, and having developed arteannuin and derivant thereof is the effective antimalarial agent compositions of a class.In recent years, along with to the going deep into of arteannuin and derivant research thereof, constantly found its application in frontier.
The purpose of this invention is to provide a kind of efficient, safety and the treatment lupus erythematosus that has no side effect and the pharmaceutical composition of photosensitive diseases.
The present invention is based on such fact and finishes: the inventor is devoted to malaria research with the dihydroarteannuin of its invention, the result proves that dihydroarteannuin is efficiently, low toxicity, aspect such as easy to prepare all is better than other artemisinin derivatives, simultaneously obtain new discovery in the immune Research field again, promptly finding that dihydroarteannuin has remarkable immunosuppressant and pair cell immunity and humoral immunization and has on the basis of dual regulation, through pharmacodynamics and clinical research proof dihydroarteannuin lupus erythematosus and photosensitive diseases are had sure curative effect, and do not have obvious toxic and side effects.
The invention provides a kind of pharmaceutical composition that contains dihydroarteannuin that is used for the treatment of lupus erythematosus and photosensitive diseases, said composition contains the dihydroarteannuin for the treatment of effective dose.
The purpose of this invention is to provide a kind of pharmaceutical composition that contains dihydroarteannuin that is used for the treatment of lupus erythematosus and photosensitive diseases, said composition contains dihydroarteannuin 1-10 weight %.
Pharmaceutical composition of the present invention is applicable to all lupus erythematosus (systemic lupus erythematosus (sle) and discoid lupus erythematosus) and photosensitive diseases (polymorphous light eruption etc.).
Pharmaceutical composition of the present invention can be any medicine type commonly used, can be solid preparation, and for example tablet, capsule, suppository, powder, granule, transdermal ointment, cream etc. also can be liquid preparation, for example oral liquid, spray, injection etc.Preparation of drug combination mode of the present invention is that those of ordinary skill in the art is known.
According to pharmaceutical composition of the present invention, preferably be made into tablet or capsule, each sheet tablet or each capsules contain the dihydroarteannuin of 20-80mg.
Pharmaceutical composition of the present invention is generally oral administration, also can for example treat light sensitive dermatoses and can use external preparation through other administrations.Consumption is generally the 1-5mg/kg body weight/day.
Pharmaceutical composition of the present invention can use separately.When the heavier systemic lupus erythematosus (sle) of treatment symptom, also can with the other drug of existing treatment lupus erythematosus and photosensitive diseases, for example Chang Yong hormone medicine is used in combination.
The preparation method of the dihydroarteannuin that the present invention uses is known.Relevant its preparation method is seen in bibliographical information.
Below example further illustrates the present invention by experiment.But it should be understood that experimental example of the present invention just is used for explanation rather than restriction the present invention.Pharmacodynamic experiment
Pharmaceutical composition of the present invention is to lupus mice (BXSB) Immune Effects
Materials and methods: (one) animal
Draw from the breadboard BXSB lupus of U.S. Jackson mice.(2) medicine
1, the pharmaceutical composition that contains dihydroarteannuin of the present invention.
2, be purchased prednisone.(3) main agents and equipment:
1, sodium lauryl sulphate
2、CBBG
250
3, standard protein reagent
4, OKT
4OKT
8The monoclonal body
αL
3T
4αL
YT
2
5, the anti-Mus Ig of FITC-antibody
6, mouse lymphocyte separating medium
7, uv-spectrophotometric instrument
8, fluorescence microscope
9, (four) administrated method such as centrifuge:
1, route of administration: irritate stomach, once a day
2, dose: (1) pharmaceutical composition 25mg/kg/d of the present invention
(2) prednisone 6.3mg/kg/d
Successive administration 15 days, 30 days, 45 days.(5) experimental technique:
The 10-11 BXSB male mice in age in week that to select 30 body weight be 22-25g is divided into three groups: matched group (10), pharmaceutical composition group of the present invention (10), prednisone group (10).
1, the mensuration of urine protein:
Compressing bladder method is got Mus urine, gets urine before medication, respectively after medication 15 days then, 30 days, gets urine in 45 days.
The Marcart method is measured: urine 100ml is added be mixed room temperature 20 minutes of CBBG250 that 4ml contains sodium lauryl sulphate, is contrast with standard protein liquid, detects at ultraviolet light spectrophotometer 600nm absorbance value.
2, spleen weight changes:
After the BXSB mouse medication 45 days, disconnected neck killed mice, gets spleen and weighs.
3, spleen t lymphocyte subset heap sort
(1) getting mice spleen grinds, filters;
(2) lymphocyte layering liquid is removed erythrocyte, keeps single nucleus;
(3) wash single nucleus with a large amount of Hank ' s liquid; (4) cell counting; (5) with the culture fluid that contains calf serum cell is made into 1 * 10
7Suspension; (6) cell suspension is placed little centrifuge tube; (7) 5000rpm is centrifugal, removes supernatant; (8) add monoclonal antibody (α L respectively
3T
4α L
YT
2) 4 ℃, 30 ' (9) is centrifugal, adds the fluorescence washing liquid and wash from 2 times; (10) add fluorescent antibody, 4 ℃, 30 '; (11) the fluorescence washing liquid is washed from twice; (12) add fluorescence preservation liquid and be kept at 4 ℃; (13) fluorescence microscope is observed counting down.4, B cell detection (1) is got spleen and is ground filtration; (2) lymphocyte layering liquid separates single nucleus; (3) wash from cell 2 times with 0.01MPB (PH7.4); (4) be made into 2-3 * 10 with the 0.01MPAS that contains 5% calf serum
6Cell suspension; (5) labeled cell 4 ℃, left standstill 30 minutes with in FITC one anti-mice sIg antibody and the cell suspension; (6) Cell sap 0.01MPBS (PH7.4) contains 5% calf serum, and 37 ℃ (pre-temperature) washes from twice; (7) fluorescence microscope is observed counting down; The result: 1, see the following form 1 with not medication group urine protein testing result before and after the BXSB mouse medication: table 1 pharmaceutical composition of the present invention is to the influence of mouse retention albumen (OD)
| Size of animal (only) | Before the medication | After the medication | |||
| 15 days | 30 days | 45 days | |||
| Matched group | 10 | 89 | 90.6 | 110.33 | 119.33 |
| Of the present invention group | 10 | 89.5 | 86.25 | 82.2 | 78.8 |
| The prednisone group | 10 | 88.75 | 83.35 | 79.66 | 63.3 |
The result shows that after using pharmaceutical composition of the present invention, the urine protein that is tried mice descends, and behind the use prednisone, the urine protein of mice descends more, but toxic and side effects is big.
2, spleen weight
Table 2 pharmaceutical composition of the present invention is to the influence of mice spleen weight
3, T cell subsets and B cell table 3 pharmaceutical composition of the present invention are to the influence of T cell subsets and B cell
| Size of animal (only) | X+S | Variance analysis | |
| Matched group | 10 | 0.16±0.02 | P＜0.05 |
| Of the present invention group | 10 | 0.13±0.03 | |
| The prednisone group | 10 | 0.11±0.02 |
| Size of animal (only) | X+S | |||
| αL 3T 4 | αL YT 2 | B | ||
| Matched group | 10 | 40.54±7.18 | 35.54±7.7 | 31.22±10.36 |
| Of the present invention group | 10 | 46.8±8.65 | 41.98±12.09 | 21.25±4.02 |
| The prednisone group | 10 | 30.68±9.14 | 30.18±1.97 | 22.13±4.98 |
| Variance analysis | P＜0.001 | P＜0.05 | P＜0.05 | |
Result of the test shows that pharmaceutical composition of the present invention and prednisone have the effect that reduces the BXSB mouse urine protein, and can alleviate the spleen weight of BXSB mouse, and the former acts on a little less than the latter.Show that with classification of T cell subsets and B cell quantity in the BXSB mouse of matched group dihydroarteannuin has the quantity of each subgroup of raising T cell, reduces the B cell quantity simultaneously.And prednisone not only reduces the quantity of B cell quantity but also each subgroup of reduction T cell.The prompting dihydroarteannuin reduces the autoimmune disease that immune complex deposit causes under the situation that reduces B emiocytosis sIg, also may have the immunological disease function that improves the T cell, and immune dual regulation is promptly arranged.Though prednisone has reduced the B cell quantity, but also suppressed each subgroup quantity of T cell, this explanation prednisone treatment BXSB mouse is a kind of immune system that suppresses fully, therefore take for a long time and can reduce body's immunological function, both compare, and select for use during BXSB mouse the pharmaceutical composition that contains dihydroarteannuin of the present invention more suitable in treatment.Toxicity test acute toxicity testing (mice): LD
50834.5mg/kg sub-acute toxicity test (Canis familiaris L.):
By 11,33,99mg/kg/ days three dosage groups administration one month, through clinical behavior observation, multinomial blood parameters inspection and main organs pathological examination, the result show before the administration of big-and-middle dosage group weight ratio slightly descend, other every showing no obvious abnormalities.Long term toxicity test (rat):
By 280,93,31mg/kg/ days 24 weeks of three dosage groups administration, through clinical behavior observation, hematological examination, serum biochemistry is learned and is checked, main organs is checked, pathological examination, the result shows except that heavy dose of group (quite people's consumption is 175 times) renal function (creatinine) changes, other every showing no obvious abnormalities.Clinical experiment
With patient's 100 examples such as medicine composite for curing lupus erythematosus that contain dihydroarteannuin of the present invention, obvious effective rate 44%, total effective rate 94%.Clinical diagnosis standard and clinical efficacy evaluation criteria were by health ministry standard in 1994.
1, produce effects: skin lesion disappears (can leave over pigmentation) fully, and local pathologic finding corium inflammation disappears no liquefaction of basal cell.
2, effective: skin lesion disappears more than 50%, and local pathologic finding improves.
3, invalid: treat three courses of treatment, skin lesion and tissue pathology checking do not have improvement or increase the weight of.
Clinical research is the result show, pharmaceutical composition of the present invention all has very significantly curative effect for treatment lupus erythematosus and photosensitive diseases.Pharmaceutical composition of the present invention is especially obvious to the various heliosensitivity erythema skin lesion effect that disappears, and biochemical and pathological examination project also has the improvement of varying degree to General Symptoms such as arthralgia and other.And this medicine safety range is big, does not clinically see obvious toxic-side effects.
More than describe the present invention.But it should be understood that for those of ordinary skill of the present invention, can under the prerequisite that does not depart from spirit of the present invention, the present invention be revised and improve that these corrections and improvement all belong to protection scope of the present invention.
Claims (7)
1. the application of dihydroarteannuin in preparation treatment lupus erythematosus and photosensitive diseases pharmaceutical composition.
2. application according to claim 1, wherein said compositions contains the dihydroarteannuin of 1-10 weight %.
3. application according to claim 1, wherein said compositions are solid preparation.
4. application according to claim 3, wherein said solid preparation are oral formulations.
5. application according to claim 1, wherein said compositions are liquid preparation.
6. application according to claim 5, wherein said liquid preparation are oral formulations.
7. application according to claim 1, wherein said compositions are external preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99103346 CN1116036C (en) | 1999-03-16 | 1999-03-16 | Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99103346 CN1116036C (en) | 1999-03-16 | 1999-03-16 | Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1266683A CN1266683A (en) | 2000-09-20 |
| CN1116036C true CN1116036C (en) | 2003-07-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99103346 Expired - Lifetime CN1116036C (en) | 1999-03-16 | 1999-03-16 | Medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8013011B2 (en) * | 2005-10-20 | 2011-09-06 | Epipharm Gmbh | Treatment and prevention of benign pigmented moles (naevi) using artemisinine and the derivatives thereof |
| CN103181886A (en) * | 2011-12-30 | 2013-07-03 | 上海复星医药产业发展有限公司 | Artemisinin or its derivative sustained release preparation, and preparation method thereof |
| CN103181901A (en) * | 2011-12-30 | 2013-07-03 | 桂林南药股份有限公司 | Dihydroartemisinin controlled-release preparation used for treating lupus erythematosus |
| CN105213321B (en) * | 2015-10-28 | 2018-08-14 | 海南澋润生物科技有限公司 | A kind of medicinal-bathing particle agent and application thereof of qinghaosu or derivatives thereof |
| CN106928274B (en) * | 2017-02-28 | 2019-09-10 | 东南大学 | A kind of dihydroartemisinine diploid derivative, its pharmaceutical composition and application |
| CN111617070A (en) * | 2019-06-11 | 2020-09-04 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for treating inflammation caused by streptococcus suis virulence protein |
| CN112755019B (en) * | 2021-01-19 | 2022-02-18 | 首都医科大学附属北京佑安医院 | Application of dihydroartemisinin in preparation of medicine for inhibiting over-immune activation caused by poor immune reconstitution |
-
1999
- 1999-03-16 CN CN 99103346 patent/CN1116036C/en not_active Expired - Lifetime
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| Publication number | Publication date |
|---|---|
| CN1266683A (en) | 2000-09-20 |
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Effective date of registration: 20161216 Address after: 650106 Kunming science and Technology Industrial Development Zone, Yunnan Province Road No. 166 Patentee after: Kun Yao Group Plc Address before: 100027 Beijing, Sanlitun, south of the 39 floor, the 10 group of Patentee before: Tu Youyou Patentee before: Yang Lan |
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Granted publication date: 20030730 |
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