CN103599121A - Application of engeletin in preparation of drug for treating or preventing diabetes pathogenic stroke - Google Patents
Application of engeletin in preparation of drug for treating or preventing diabetes pathogenic stroke Download PDFInfo
- Publication number
- CN103599121A CN103599121A CN201310601049.8A CN201310601049A CN103599121A CN 103599121 A CN103599121 A CN 103599121A CN 201310601049 A CN201310601049 A CN 201310601049A CN 103599121 A CN103599121 A CN 103599121A
- Authority
- CN
- China
- Prior art keywords
- engelitin
- application
- mice
- group
- engeletin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides novel application of engeletin in drugs, and particularly relates to application of engeletin in preparation of a drug for treating or preventing diabetes pathogenic stroke. According to the application, 25 to 1000mg of engeletin is adopted, and 25 to 500mg is preferable. Engeletin is in a form of tablet, pill, granules, capsule, syrup, soft capsule and other forms, and the forms of capsule and tablet are preferable.
Description
Technical field
The present invention relates to a kind of new medicine use, relate to particularly the application of engelitin in the medicine of preparation treatment or prevent diabetes originality apoplexy.
Background technology
Apoplexy is one of major disease of serious harm human health, and the people of whole world sixth can at least meet with apoplexy one time in its life process, is the major reason that adult is dead and disable.Diabetes are a kind of extra high risk factors of patient that apoplexy occurs for the first time, especially the probability that for type 2 diabetes mellitus patient, apoplexy occurs is than the high 2-5 of non-type 2 diabetes mellitus patient times of [Zafar A, Shahid SK, Siddiqui M, Khan FS.Pattern of stroke in type 2 diabetic subjects versus non diabetic subjects.J Ayub Med Coll Abbottabad.2007; 19 (4): 64-67.], and wherein the last 70% patient that apoplexy occurs has obvious diabetes or prediabetes, comprise impaired fasting glucose (IFG) (IFG) and impaired glucose tolerance (IGT) [Kernan WN, Inzucchi SE.Type 2 diabetes mellitus and insulin resistance:stroke prevention and management.Curr Treat Options Neurol 2004; 6:443-450], so the simple non-diabetic originality of the hazard ratio apoplexy that the apoplexy that merges type 2 diabetes mellitus causes is much bigger, especially the nearest change along with living standards of the people and life style, China type 2 diabetes mellitus patient is explosive growth, and the acute diabetes complication admission rate of seeing and treating patients exceeds three times than the U.S.." [Alcorn T, Ouyang Y.Diabetes saps health and wealth from China ' s rise.Lancet.2012; 379 (9833): 2227-2278.], so the treatment of type 2 diabetes mellitus originality apoplexy is seemed to particularly important.
Rhizoma Smilacis Glabrae is the dry rhizome of liliaceous plant smilacis glabra Smilax glabra Roxb..The ground such as on the south the distribution Yangtze river basin, Rhizoma Smilacis Glabrae slightly sweet flavor is flat.Nontoxic.Return liver, stomach warp.There is dehumidifying, removing toxic substances, the effects such as easing joint movement, for limbs contracture, the bones and muscles pain due to syphilis and mercurialism, damp and hot pouring worm, leukorrhagia, carbuncle, scabies, scrofula, scabies.< < Compendium of Materia Medica > > say again its " strengthening the spleen and stomach, bone and muscle strengthening, curing rheumatism, sharp joint, stopping leak rushes down.Control contracture osteodynia, malignant boil carbuncle.Separate hydrargyrum powder, Vermilion poison ".Engelitin is to extract from Rhizoma Smilacis Glabrae, the effective ingredient that separation obtains.Engelitin has effect [the Ruangnoo S such as antiinflammatory, Jaiaree N, Makchuchit S, Panthong S, Thongdeeying P, Itharat A.An in vitro inhibitory effect on RAW 264.7 cells by anti-inflammatory compounds from Smilax corbularia Kunth.Asian Pac J Allergy Immunol.2012; 30 (4): 268-274.], but engelitin has no report in the pharmacological action of preparation treatment or prevent diabetes originality apoplexy, the inventor, by a large amount of experimentatioies, has found the application of engelitin in the medicine of preparation treatment or prevent diabetes originality apoplexy.
Summary of the invention:
The invention provides the application of engelitin in the medicine of preparation treatment or prevent diabetes originality apoplexy.
The invention provides engelitin and prepare the application in the medicine for the treatment of or prevent diabetes originality apoplexy acute attack stage.
The invention provides the application of engelitin in the medicine of preparation treatment or prevent diabetes originality stroke in convalescent stage.
Pharmaceutical composition provided by the invention is when for diabetes originality apoplexy, and when oral, using dosage scope is 25mg～1000mg; Preferred 25～500mg.
When medicine provided by the invention exists with dosage form, the content of its effective ingredient is 25～100mg.
Pharmaceutical composition provided by the invention can add corresponding adjuvant according to preparation needs, with forms such as tablet, pill, granule, capsule, syrup, soft capsules, exists, and is preferably capsule and tablet.Various dosage form provided by the invention all can adopt pharmacy conventional method to be prepared from.
The inventor has carried out following test and has confirmed the application in treatment or the medicine of prevent diabetes originality apoplexy.(the following examples are used for more detailed description the present invention, but and do not mean that the present invention only limits to this).
Concrete embodiment:
The preparation of preparation example 1 engelitin tablet
Prescription:
Operation: cross 100 mesh sieves after taking the abundant mix homogeneously of engelitin, Icing Sugar, lactose and carboxymethyl starch sodium of recipe quantity, add 3%PVP
k30aqueous solution is soft material processed in right amount, and 20 mesh sieves are granulated, 60 ℃ dry 3 hours, 18 mesh sieve granulate, add the magnesium stearate of recipe quantity, tabletting after mix homogeneously, every agreement that contracts a film or TV play to an actor or actress 200mg, obtains.
The preparation of preparation example 2 engelitin capsules
Prescription:
Operation: the engelitin that takes recipe quantity adds soft capsule processed after the abundant mix homogeneously of carboxymethyl starch sodium, and every about 200mg, obtains.
The impact of test example 1 engelitin on type 2 diabetes mellitus model mice acute cerebral ischemia
1.1 material
Laboratory animal: Jackson Lab laboratory db/db diabetic mice (is purchased from Nanjing model animal institute, kind: db/db mice; Strain: BKS.Cg-Dock7m+ /+Leprdb/J; Animal grade: SPF).
Medicine: engelitin, Shandong Province's natural drug Engineering Technical Research Centre, content 99%, lot number: 110210;
Red tetrazolium: U.S. Sigma company product, is made into 4% solution with normal saline before use.
1.2 test methods and result
(2) method and result:
70 db/db diabetic mices are divided into model control group (normal saline), Edaravone intravenously administrable group (ED, 5mg/kg), engelitin gastric infusion group 1 (5mg/kg), engelitin gastric infusion group 2 (10mg/kg), engelitin gastric infusion group 3 (20mg/kg), engelitin gastric infusion group 4 (50mg/kg), engelitin gastric infusion group 5 (100mg/kg) at random.Every group 10, engelitin gastric infusion successive administration 3 days, fasting in 8 hours after the 2nd administration, after fasting 16 hours, chloral hydrate (350mg/kg, i.p.) is anaesthetized separated right carotid, folder closes in neck, common carotid artery, external carotid artery proximal part and distal end ligation, and cut off centre.External carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire, length 5.0cm) is inserted into intracranial by external carotid artery, while meeting slight resistance, stop, insertion depth is about 2cm.Ligation external carotid artery opening, and open common carotid artery bulldog clamp, disinfection and stitching wound, causes right side middle cerebral artery ischemia model; Matched group only carries out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.2 hours intravenously administrables after the modeling of Edaravone intravenously administrable group, all the other operate with above-mentioned each group.After 24 hours, press document [Liu little Guang, Xu Lina, a kind of mouse brain medium-sized artery model that can evaluate thrombolytic and anti-thrombolytic, Acta Pharmaceutica Sinica, 1995,30:662] described method and standard observe and record the behavior disorder of mice: (A) carry Mus tail and observe forelimb flexing situation, as two forelimb symmetries are stretched to ground, count 0 minute, as wrist flexing appears in operation offside forelimb, count 1 minute, elbow flexing is counted 2 minutes, shoulder inward turning is counted 3 minutes, existing wrist flexing and/or elbow flexing, have again shoulder inward turning person, counts 4 minutes.(B) animal is placed on plane earth, pushes away respectively both shoulders to side shifting, check resistance.As bilateral resistance equity and strong, count 0 minute, resistance descender when promoted to operation offside, according to decline degree difference be divided into gently, in, weigh three degree, count respectively 1,2 and 3 minute.(C) the two forelimbs of animal are put on a wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 minute.According to operation offside muscular tension decline degree difference, count 1,2 and 3 minute equally.(D) animal has ceaselessly to a side person of turn-taking, and counts 1 minute.According to standard scoring, full marks are 11 minutes, and mark is higher, represent that animal behavior obstacle is more serious.
After behavior scoring, put to death mice, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, brain is red tetrazolium (TTC) dyeing for sheet, after normal structure is dyed, takes on a red color, and blocking tissue is white in color, after dyeing, take a picture, with China Aviation space flight university pathological image analysis software, ask infarct size ratio.Data with
represent, ischemia face, relatively to adopt SAS9.0 to carry out one factor analysis of variance between group, relatively adopts non parametric tests between neurobehavioral defect group, and P < 0.05 represents that difference has significant.
Result is as shown in table 1, and ischemia is after 24 hours, and db/db diabetic model group mice shows obvious behavior disorder, and obvious kitchen range shape ischemic region also appears in cerebral tissue, reaches full brain 30% left and right.Engelitin gastric infusion group 1 (5mg/kg), engelitin gastric infusion group 2 (10mg/kg), engelitin gastric infusion group 3 (20mg/kg), engelitin gastric infusion group 4 (50mg/kg), engelitin gastric infusion group 5 (100mg/kg) is significantly improved mice behavior disorder, reduce ischemic areas (with model group comparison, p < 0.05 or p < 0.01), engelitin gastric infusion group 4 (50mg/kg) compares with engelitin gastric infusion group 5 (100mg/kg), to improving mice behavior disorder, reduce ischemic areas no significant difference (p > 0.05).
Table 1 engelitin is on the impact of mouse brain ischemic injuries (n=10)
| Group | Dosage (mg/kg) | Behavior disorder | Ischemic areas (%) |
| Matched group | --- | --- | --- |
| Model group | -- | 9.3±1.5 | 28.4±5.9 |
| Edaravone intravenously administrable group | 5 | 7.7±1.2 * | 21.7±5.4 * |
| Engelitin gavage group 1 | 5 | 7.6±1.1 * | 22.0±5.0 * |
| Engelitin gavage group 2 | 10 | 6.9±1.4 ** | 20.1±3.9 ** |
| Engelitin gavage group 3 | 20 | 6.2±0.8 ** | 17.3±4.8 ** |
| Engelitin gavage group 4 | 50 | 5.3±1.1 ** | 15.0±4.5 ** |
| Engelitin gavage group 5 | 100 | 5.1±1.2 ** | 14.6±3.9 ** |
*, p < 0.05,
*, p < 0.01, with model group comparison
Test the impact of 2 engelitins on the long-term functional rehabilitation of type 2 diabetes mellitus model mice cerebral ischemia
2.1 material
Laboratory animal: Jackson Lab laboratory db/db diabetic mice (is purchased from Nanjing model animal institute, kind: db/db mice; Strain: BKS.Cg-Dock7m+ /+Leprdb/J; Animal grade: SPF).
Medicine: engelitin, Shandong Province's natural drug Engineering Technical Research Centre, content 99%, lot number: 110210;
The IgG of the anti-mice of biotin (two is anti-, and Foochow steps neoplasm technology Chinese companies); Anti-NeuN serum (Beijing Bo Aosen biotech company)
2.2 test methods and result
50 db/db diabetic mices, chloral hydrate (350mg/kg, i.p.) anesthesia, separated right carotid, folder closes in neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off centre.External carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire, length 5.0cm) is inserted into intracranial by external carotid artery, while meeting slight resistance, stop, insertion depth is about 2cm.Ligation external carotid artery opening, and open common carotid artery bulldog clamp, disinfection and stitching wound, causes right side middle cerebral artery ischemia model; 10 animals of matched group only carry out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.Animal brain ischemia after 24 hours 40 animal patterns be divided into model control group (normal saline), engelitin gastric infusion group 1 (5mg/kg), engelitin gastric infusion group 2 (20mg/kg), engelitin gastric infusion group 3 (100mg/kg).Fill with again after 14 days, 3,7 and 14 days neural behavioral deficiencies of Evaluation administration, mice is put to death in last administration, gets brain, SABC is measured microvessel density (MVD) and is carried out NeuN dyeing, the evaluation type 2 diabetes mellitus model mice administration 14 days recovery situation to the long-term function of cerebral ischemia.
Evaluate neurobehavioral defect and comprise fore paw functional impairment determination experiment, beam walking experiment and rubberized fabric adhere experiment.Fore paw functional impairment is measured according to [De Ryck M, Van Reempts J, Borgers M, Wauquier A, Janssen PAJ.Photochemical stroke model:flunarizine prevents sensorimotor deficits after neocortical infarcts in rats.Stroke, 1989,20 (10): 1383-1390.] detect the posture of mice upper body part while hanging Mus tail; In the test of pawl functional impairment, first mention left front pawl or right front pawl, offside fore paw or rear solid end stretch to bodyside, the difference of again stretching required time according to each pawl is scored as 0 (< 1s), 1 (> 2s), 2 (can not stretch).Take after ischemia 7d and 14d as observing time point detect respectively.
Beam walking experimental basis list of references [Feeney DM, Gonzalez A, Law WA.Amphetamine, haloperidol and experience interact to affect the rate of recovery after motor cortex injuries.Science, 1982, 217 (4562): 855-857.] carry out, beam is wide is 2.0cm, long is 120cm, thickness is 1cm, beam is 80cm apart from ground, the unsettled placement of beam level, beam one end connects a magazine (long 40cm, wide 22cm, high 20cm), with high light, stimulate and impel mice to come into magazine by beam.Standards of grading: 0 minute, mice can not rest on beam, directly falls down; 1 minute, mice can rest on beam, but can not walk about; 2 minutes, mice was attempted by beam, but from beam, threw in the process of walking about; 3 minutes, mice can walk upper cord, but the number of times of the hind leg landing of damaged surpasses half; 4 minutes, the mice beam of can passing by, the number of times of hind leg landing surpasses 1 time but less than half; 5 minutes, the mice beam of can passing by, only threw 1 time from beam; 6 minutes, the mice beam of can passing by smoothly.Animal is trained 2d before ischemia, allows the mice association beam of can passing by smoothly of undergoing training.Take 3d, 7d after ischemia, 14d carries out beam walking experiment to each group ischemia mice respectively as time point of observation.
Rubberized fabric adhere experimental basis [Schallert T, Upchurch M, Lobaugh N, Farrar SB, Spirduso WW, Gilliam P, Vaughn D, Wilcox RE.Tactile extinction:distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage.Pharmacol Biochem Behav, 1982, 16 (3): 445-462.], the left fore wrist facies ventralis that the medical proof fabric of 0.7 * 0.7cm size of usining is attached to ischemia mice is as tactual stimulation, the uncomfortable idea of mice removes adhesive plaster, record ischemia mice and remove incubation period of adhesive plaster.Preoperative exercise 2d, 1 times/day, the mice that makes to undergo training can complete the action that removes adhesive plaster in 20s, can not complete the mice rejecting that removes adhesive plaster action in 20s.Take 3d, 7d after ischemia, 14d detects as time point of observation carries out respectively rubberized fabric adhere experiment.Standards of grading: 1 minute, remove adhesive plaster time < 10s; 2 minutes, removing the adhesive plaster time was 10-19s; 3 minutes, removing the adhesive plaster time was 20-29s; 4 minutes, removing the adhesive plaster time was 30-39s; 5 minutes, removing the adhesive plaster time was 40-49s; 6 minutes, removing the adhesive plaster time was 50-59s; 7 minutes, remove adhesive plaster time > 60s.
The assay method of MVD is pressed [the Weidner N such as Weidner, Semple JP, Welch WR, Folkman J.Tumor angiogenesis and metastasis-correlation in invasive breast carcinomas.N Engl J Med, 1991, 324 (1): 1-8.] method providing is measured, every single endotheliocyte that is dyed to brown color or endotheliocyte are bunch as a vascular counts, rather than take and occur that lumen of vessels is as unique counting standard, count microvascular quantity in each visual field, then get the average in 3 visuals field as the result of measuring MVD.
NeuN colouring method is by [Jiang WL, Zhang SP, Fu FH, Zhu HB, Hou J.Inhibition of nuclear factor-κ B by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion.J Neuroinflammation.2010; 7:55]: crown section (5 μ M) is carried out NeuN dyeing by hatching, has anti-NeuN dyeing blood cleer and peaceful 3,3-diaminobenzidine four hydrochlorates (DAB).First, crown section at room temperature TBS buffer solution (0.15M sodium chloride, the Tris-HCl of 0.1 meter, pH value 7.5) wash twice, each 20 minutes.Secondly in culture fluid of TBS-BSA [TBS containing 1% (W/V) BSA and 3% normal goats serum (NGS)] temperature, incubate and within 30 minutes, stop non-specific antibody combination.At 1: 500, anti-NeuN serum (Beijing Bo Aosen biotech company) spent the night in section, 4 ℃ of 1%NGS dilutions, TBS dilution through three times 10 minutes 1%NGS is rinsed, (two is anti-for the IgG of section and 1: 250 anti-mice of biotin, Foochow steps neoplasm technology Chinese companies) in the TBS of 1%NGS solution temperature, to incubate, NeuN dyes to calculate cerebral infarction volume and calculates.
Table 2 engelitin on the cerebral ischemia of type 2 diabetes mellitus model after the impact of neurobehavioral defect
Note: with model group comparison
*p < 0.05,
*p < 0.01.
Table 3 engelitin on the cerebral ischemia of type 2 diabetes mellitus model after the impact of 14 days MVD and infarct size
Claims (5)
1. the application of engelitin in the medicine of preparation treatment or prevent diabetes originality apoplexy.
2. the application of engelitin in the medicine of preparation treatment or prevent diabetes originality apoplexy acute attack stage.
3. the application of engelitin in the medicine of preparation treatment or prevent diabetes originality stroke in convalescent stage.
4. engelitin is when for diabetes originality apoplexy, and when oral, using dosage scope is 25mg～1000mg; Preferred 50～500mg.
5. engelitin exists with forms such as tablet, pill, granule, capsule, syrup, soft capsules, is preferably capsule and tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310601049.8A CN103599121B (en) | 2013-11-18 | 2013-11-18 | Application in preparation treatment or prevention diabetes originality apoplexy medicine for the engelitin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310601049.8A CN103599121B (en) | 2013-11-18 | 2013-11-18 | Application in preparation treatment or prevention diabetes originality apoplexy medicine for the engelitin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103599121A true CN103599121A (en) | 2014-02-26 |
| CN103599121B CN103599121B (en) | 2016-11-09 |
Family
ID=50117430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310601049.8A Expired - Fee Related CN103599121B (en) | 2013-11-18 | 2013-11-18 | Application in preparation treatment or prevention diabetes originality apoplexy medicine for the engelitin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103599121B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732559A (en) * | 2016-03-10 | 2016-07-06 | 滨州医学院 | Engeletin derivative and method for preparing same |
-
2013
- 2013-11-18 CN CN201310601049.8A patent/CN103599121B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 白梅等: "HPLC 测定不同产地土茯苓中落新妇苷和黄杞苷含量", 《药物分析杂志》, vol. 3, no. 8, 31 August 2013 (2013-08-31), pages 1352 - 1354 * |
| 陈红梅等: "土茯苓的化学与药理研究进展", 《中国民族医药杂志》, no. 11, 30 November 2008 (2008-11-30), pages 71 - 73 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732559A (en) * | 2016-03-10 | 2016-07-06 | 滨州医学院 | Engeletin derivative and method for preparing same |
| CN105732559B (en) * | 2016-03-10 | 2020-07-07 | 滨州医学院 | Engelhardin derivative and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103599121B (en) | 2016-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101785844B (en) | Traditional Chinese medicine combination and preparation method thereof for dysentery treatment | |
| CN101785850A (en) | Traditional combination and preparation method thereof for intestinal obstruction treatment | |
| CN101773634A (en) | Chinese medicine composition for treating abdominal distention and fullness and preparation method thereof | |
| CN101810835A (en) | Chinese medicinal composition for treating purpura and preparation method thereof | |
| CN105497620A (en) | Health-care traditional Chinese medicine preparation for weight reduction and body building | |
| CN101773649B (en) | Chinese medicine composition for treating acute abdomen and preparation method thereof | |
| CN101406688A (en) | Compound formulation for treating rheumatic arthritis and rheumatoid arthritis | |
| CN104547532A (en) | Traditional Chinese medicine preparation for treating migraine and preparation method of traditional Chinese medicine preparation | |
| CN101822814A (en) | Traditional Chinese medicine composition for treating lung failure and preparation method thereof | |
| CN104524247B (en) | One treats migrainous medical composition and its use | |
| CN107320475A (en) | GCV is preparing the application in treating or preventing glycosuria pathogenicity apoplectic thing | |
| CN105194301A (en) | Traditional Chinese medicine preparation for treating chronic cardiac failure | |
| CN103599121A (en) | Application of engeletin in preparation of drug for treating or preventing diabetes pathogenic stroke | |
| CN104547560A (en) | Medicine for treating gastric diseases and preparation method thereof | |
| CN103768082B (en) | Astilbin merges the application in apoplexy medicine in preparation treatment or prevention diabetes | |
| CN104800675A (en) | Medicament for treating active ulcerative colitis | |
| CN104306948A (en) | Medicament composition for treating gouty arthritis | |
| CN105641191A (en) | Orally-taken medicine for treating fracture and soft tissue contusion at preliminary stage | |
| CN104958410A (en) | Traditional Chinese medicine navel sticking external plaster for treating infantile diarrhea and application sheet containing traditional Chinese medicine navel sticking external plaster | |
| CN105641057A (en) | Medicine composition for treating primary glomerular hematuria caused by failure of spleen to control blood vessels | |
| CN104383468A (en) | Dizziness relieving and resuscitation inducing preparation for infantile convulsions and preparation method of dizziness relieving and resuscitation inducing preparation | |
| CN105168366B (en) | A kind of medicament purposes in the medicine of preparation treatment female infertility | |
| CN103877506A (en) | Medicament for treating epilepsy | |
| CN103381247B (en) | Traditional Chinese medicinal composition for treating psoriasis | |
| CN102652806A (en) | Traditional Chinese medicine for treating anaphylactic purple macula |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20161109 Termination date: 20181118 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |