CN1266683A - 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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- CN1266683A CN1266683A CN 99103346 CN99103346A CN1266683A CN 1266683 A CN1266683 A CN 1266683A CN 99103346 CN99103346 CN 99103346 CN 99103346 A CN99103346 A CN 99103346A CN 1266683 A CN1266683 A CN 1266683A
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- 201000004700 rosacea Diseases 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 31
- 206010025135 lupus erythematosus Diseases 0.000 claims description 21
- 229930187998 Dihydroarteannuin Natural products 0.000 claims description 19
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- 238000002360 preparation method Methods 0.000 claims description 10
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- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 7
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
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Abstract
A medicinal composition containing dihydroartemisine for treating rosacea and photosensitive diseases features high curative effect, high safety and no toxic by-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, interior 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 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, and the consumption of adult patients is preferably 60-80mg for each person every 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 erythematosus mice (BXSB) Immune Effects
Materials and methods: (one) animal
Draw from the breadboard BXSB lupus erythematosus 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
4?αL
YT
2
5, the anti-Mus Ig of FITC-antibody
6, mouse lymphocyte liquid
7, uv-spectrophotometric instrument
8, fluorescence microscope
9, centrifuge (four) administrated method:
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) centrifugal, add 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) gets spleen and grind, filter;
(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 50% calf serum
6Cell suspension;
(5) labeled cell 4 ℃, leaves standstill 30 with in FITC one anti-mouse antibodies and the cell suspension
Minute;
(6) Cell sap 0.01MPBS (PH7.4) contains 5% calf serum, 37 ℃ (pre-temperature), wash 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 medication of BXBB mice:
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
| 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 |
3, T cell subsets and B cell
Table 3 pharmaceutical composition of the present invention is to the influence of T cell subsets and B cell
| 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 and the prednisone that contains dihydroarteannuin of the present invention has 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 arteannuin has the quantity of each subgroup of raising cell, reduces the B cell quantity simultaneously.And prednisone not only reduces the quantity of B cell quantity but also low each subgroup of T cell of resistance.The prompting arteannuin 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 in full accord, 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 that organizing renal function (creatinine) except that heavy dose of (quite people's consumption is 175 times) has the tangible change other every showing no obvious abnormalities.Clinical experiment
With medicine composite for curing lupus erythematosus patient 100 examples 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 is true
Dermatitis disease is disappeared, 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, tissue pathology checking does not have improvement or increases the weight of.
Clinical test results shows that pharmaceutical composition of the present invention all has very significantly curative effect for various lupus erythematosus of treatment 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 (5)
1. the pharmaceutical composition that is used for the treatment of lupus erythematosus and photosensitive diseases is characterized in that this pharmaceutical composition contains the dihydroarteannuin for the treatment of effective dose.
2. the pharmaceutical composition that requires as right 1 is characterized in that said composition contains the dihydroarteannuin of 1-10 weight %.
3. the pharmaceutical composition that requires as right 1 is characterized in that said composition is a solid preparation.
4. the pharmaceutical composition that requires as right 1 is characterized in that said composition is a liquid preparation.
5. the pharmaceutical composition that requires as right 1 is characterized in that said composition is an 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 true CN1266683A (en) | 2000-09-20 |
| CN1116036C CN1116036C (en) | 2003-07-30 |
Family
ID=5271235
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 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1116036C (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101282722B (en) * | 2005-10-20 | 2011-03-30 | 埃皮法姆有限责任公司 | Treatment and prevention of benign pigmented moles (naevi) using artemisinine and the derivatives 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 |
| 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 |
| CN105213321A (en) * | 2015-10-28 | 2016-01-06 | 海南澋润药业有限公司 | Medicinal-bathing particle agent of a kind of arteannuin or derivatives thereof and uses thereof |
| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
| CN111617070A (en) * | 2019-06-11 | 2020-09-04 | 中国农业大学 | Application of dihydroartemisinin in the preparation of medicine for treating inflammation caused by virulence protein of Streptococcus suis |
| CN112755019A (en) * | 2021-01-19 | 2021-05-07 | 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 |
| CN117180194A (en) * | 2023-10-24 | 2023-12-08 | 陕西省中医医院 | Artemisinin nanoemulsion and its preparation method and application |
-
1999
- 1999-03-16 CN CN 99103346 patent/CN1116036C/en not_active Expired - Lifetime
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101282722B (en) * | 2005-10-20 | 2011-03-30 | 埃皮法姆有限责任公司 | Treatment and prevention of benign pigmented moles (naevi) using artemisinine and the derivatives 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 |
| 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 |
| CN105213321A (en) * | 2015-10-28 | 2016-01-06 | 海南澋润药业有限公司 | Medicinal-bathing particle agent of a kind of arteannuin or derivatives thereof and uses thereof |
| 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 |
| CN106928274A (en) * | 2017-02-28 | 2017-07-07 | 东南大学 | A kind of dihydroartemisinine dliploid derivative, its pharmaceutical composition and application |
| CN111617070A (en) * | 2019-06-11 | 2020-09-04 | 中国农业大学 | Application of dihydroartemisinin in the preparation of medicine for treating inflammation caused by virulence protein of Streptococcus suis |
| CN112755019A (en) * | 2021-01-19 | 2021-05-07 | 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 |
| 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 the preparation of drugs for inhibiting excessive immune activation due to poor immune reconstitution |
| CN117180194A (en) * | 2023-10-24 | 2023-12-08 | 陕西省中医医院 | Artemisinin nanoemulsion and its preparation method and application |
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