CN104435312A - Application of Baiai capsule as intestinal transporter inhibitor - Google Patents
Application of Baiai capsule as intestinal transporter inhibitor Download PDFInfo
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- CN104435312A CN104435312A CN201410645232.2A CN201410645232A CN104435312A CN 104435312 A CN104435312 A CN 104435312A CN 201410645232 A CN201410645232 A CN 201410645232A CN 104435312 A CN104435312 A CN 104435312A
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- capsule
- bai
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- irbesartan
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- 239000002775 capsule Substances 0.000 title claims abstract description 47
- 239000003112 inhibitor Substances 0.000 title claims abstract description 37
- 230000000968 intestinal effect Effects 0.000 title claims abstract description 35
- 108010078791 Carrier Proteins Proteins 0.000 title abstract description 7
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims abstract description 26
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229960002198 irbesartan Drugs 0.000 claims abstract description 26
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims abstract description 20
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims abstract description 4
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 abstract description 26
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 abstract description 16
- 239000002671 adjuvant Substances 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 230000000694 effects Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 8
- 239000000890 drug combination Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 3
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 3
- 229960005156 digoxin Drugs 0.000 description 3
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 208000007530 Essential hypertension Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010832 independent-sample T-test Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/62—Nymphaeaceae (Water-lily family)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
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Abstract
The invention discloses application of a Baiai capsule as an intestinal transporter inhibitor. The intestinal transporter inhibitor has the inhibiting effect to an intestinal transporter, in particular P-glycoprotein (P-gp), so that the Baiai capsule can serve as the intestinal transporter inhibitor, in particular a P-gp inhibitor. The intestinal transporter inhibitor, namely the Baiai capsule, can serve as a Western medicine, in particular an adjuvant medicine of irbesartan; and thus, the Baiai capsule can be combined with the Western medicine to prevent or treat diseases.
Description
Technical field
The present invention relates to the application of a kind of Bai Ai capsule as intestinal transport body inhibitor.
Background technology
Chinese medicine and western medicine drug combination is increasingly general clinically at present, and its effect has obtained the generally accreditation of medical circle.Chinese medicine and western medicine associating can Synergistic, reduces toxic and side effects, reduces dosage, reduces medication taboo, expands subject range.But due to the chemical composition of Chinese medicine and pharmacological action very complicated, Chinese medicine and western medicine conbined usage is improper, also can lessen the curative effect, and increases side effect or causes drug-induced disease, serious even threat to life, so will evade and prophylactic agent incompatibility simultaneously.
Summary of the invention
Technical problem to be solved by this invention provides a kind of Bai Ai capsule as the application of intestinal transport body inhibitor for the state of the art.
The present invention solves the problems of the technologies described above adopted technical scheme: a kind of Bai Ai capsule is as the application of intestinal transport body inhibitor.
Wherein, described Bai Ai capsule comprises the component of following parts by weight:
Wherein, described intestinal transport body is P-glycoprotein.
Wherein, the effective dosage ranges of described intestinal transport body inhibitor is 1.5 ~ 6g/ days.
Wherein, the effective dose of described intestinal transport body inhibitor be 1.5g/ days, 3g/ days or 6g/ days.
Wherein, the effective dose of described intestinal transport body inhibitor is 3g/ days.
A kind of Bai Ai capsule is preventing and treating the application in hypertension as intestinal transport body inhibitor and irbesartan.
Wherein, the effective dosage ranges of described intestinal transport body inhibitor is 1.5 ~ 6g/ days, and the effective dose of described irbesartan is 120mg/ days.
Compared with prior art, the invention has the advantages that: the main component of Bai Ai capsule is Cacumen Platycladi, Radix Rehmanniae, Folium Artemisiae Argyi and Folium Nelumbinis, it is to intestinal transporter, especially P-glycoprotein (P-gp) is inhibited, therefore, Bai Ai capsule can serve as intestinal transport body inhibitor, especially P-gp inhibitor.Bai Ai capsule is the application of Late Cambrian of the present invention as intestinal transport body inhibitor, and namely Bai Ai capsule is pioneering as the invention that bases on practicality on intestinal transport body inhibitor, does not find that Bai Ai capsule has this application before.
Yin Baiai capsule is intestinal transport body inhibitor, and therefore can serve as the adjuvant drug of Western medicine with it, it can reduce the administration dose of Western medicine, and strengthens the drug effect of Western medicine, greatly reduces the toxic and side effects of Western medicine simultaneously.Such as, Ruo Baiai capsule serves as the adjuvant drug of irbesartan for preventing and treating hypertension, especially during essential hypertension, Bai Ai capsule can strengthen irbesartan drug effect, combine after taking a period of time, the dosage that can reduce irbesartan even cuts out irbesartan, greatly can reduce the toxic and side effects of irbesartan like this on the basis of stable curative effect.
Based on the effect of above-mentioned Bai Ai capsule, Bai Ai capsule can be applied on the drug combination with Western medicine, to prevent and treat or to prevent disease.
Accompanying drawing explanation
Fig. 1 is the inhibitory action of embodiment of the present invention Bai Ai capsule to the outer row of the digoxin mediated by P-gp on Caco-2 cell;
Fig. 2 is that embodiment of the present invention Bai Ai capsule is to the inhibitory action of the irbesartan mediated by P-gp the upper outside row of Caco-2 cell;
Fig. 3 is the Pharmacokinetic effect that the embodiment of the present invention combines the Oral Administration in Rats absorption of taking Bai Ai capsule and irbesartan.
Detailed description of the invention
Below in conjunction with accompanying drawing embodiment, the present invention is described in further detail.
The intestinal transport body inhibitor of the present embodiment is specially Bai Ai capsule, and the main component of Bai Ai capsule comprises the component of following parts by weight:
What the present embodiment specifically adopted is by Yangzijiang Pharmaceutical Group Co., Ltd produce batch be 13080642 Bai Ai capsule, the proportioning of each component of this Bai Ai capsule is in above-mentioned scope.
The effective dosage ranges of intestinal transport body inhibitor is 1.5 ~ 6g/ days, and such as 1.5g/ days, 3g/ days or 6g/ days, optimum effective dose is 3g/ days.
The intestinal transport body inhibitor of the present embodiment specifically can be applicable on the adjuvant drug of Western medicine.Such as with irbesartan drug combination to prevent and treat hypertension (especially essential hypertension), when Bai Ai capsule and irbesartan drug combination, the effective dosage ranges of intestinal transport body inhibitor is 1.5 ~ 6g/ days, and the effective dose of irbesartan is 120mg/ days.Bai Ai capsule and irbesartan can distinguish administration, also both can be prepared into for preventing and treating hypertensive combination medicine.
Specifically can from following several respects verify the present embodiment Bai Ai capsule (manufacturer: Yangzijiang Pharmaceutical Group Co., Ltd, production batch: intestinal transport body inhibitor 13080642) can be served as:
1, Caco-2 cell judges that Bai Ai capsule is the inhibitor of P-gp
Specifically utilize Caco-2 cell model and classical P-gp substrate drugs digoxin to prove that Bai Ai capsule is the inhibitor of P-gp.Prove result as shown in Figure 1, as can be seen from Figure 1, Bai Ai capsule effectively can suppress the outer row (IC of digoxin
50=0.42mg/mL).
2, Caco-2 cell model and Western medicine is utilized---irbesartan, proves that Bai Ai capsule can suppress the outer row of the irbesartan as P-gp substrate, thus improves its absorption.
Table 1 shows the substrate (complying with gram Rieter is known P-gp specific inhibitor) that irbesartan is P-gp, and this is consistent with bibliographical information.Fig. 2 then shows the outer row that Bai Ai capsule can suppress irbesartan, thus improves its intestinal absorption.
Table 1. experimental verification irbesartan is the substrate of P-gp
Above two aspects are all demonstrate Bai Ai capsule theoretically can serve as intestinal transport body inhibitor, in order to verify that Bai Ai capsule serves as intestinal transport body inhibitor further by testing, as subjects, the present embodiment SD rat verifies that Bai Ai capsule can serve as Western medicine---the adjuvant drug of irbesartan.
Use Bai Ai capsule in advance with every daily dose of 125mg/kg (being equivalent to human administration's dosage for 1.5g), 250mg/kg (being equivalent to human administration's dosage for 3g), 500mg/kg (being equivalent to human administration's dosage for 6g) to SD rat oral gavage 3 days; Half an hour after 3rd day gavage, with the dosage of 10mg/kg to SD rat oral gavage irbesartan (be equivalent to human administration's dosage and be about 120mg).Collection whole blood calculates the AUC in 0-72 hour, and adopts independent samples t test to administering drug combinations group and matched group, and namely first group of alone irbesartan group is carried out statistical analysis, and analysis result is as shown in table 2.
The analysis result of table 2. drug combination and matched group
As shown in Table 2, the Bai Ai dosage of 250mg/kg can cause irbesartan (Irbesartan) AUC to improve about twice (p<0.05), but does not cause without marked difference Cmax.And blood distiller’s yeast line as shown in Figure 3 also shows Bai Ai capsule can increase the bioavailability of irbesartan and extend curative effect.
Comprehensive above data, Bai Ai capsule all has effect to P-gp substrate drugs in P of Rats K experiment in cell experiment and body in vitro, is embodied in and improves permeability or bioavailability and reduce outer row, thus demonstrate the inhibitory action of Bai Ai capsule to P-gp.Therefore, can prove, Bai Ai capsule can be used as a kind of novel P-gp inhibitor.
Above content is only preferred embodiment of the present invention, and for those of ordinary skill in the art, according to thought of the present invention, all will change in specific embodiments and applications, this description should not be construed as limitation of the present invention.
Claims (8)
1. a Bai Ai capsule is as the application of intestinal transport body inhibitor.
2. application according to claim 1, is characterized in that, described Bai Ai capsule comprises the component of following parts by weight:
3. application according to claim 1, is characterized in that: described intestinal transport body is P-glycoprotein.
4. application according to claim 1, is characterized in that: the effective dosage ranges of described intestinal transport body inhibitor is 1.5 ~ 6g/ days.
5. application according to claim 3, is characterized in that: the effective dose of described intestinal transport body inhibitor is 1.5g/ days, 3g/ days or 6g/ days.
6. application according to claim 4, is characterized in that: the effective dose of described intestinal transport body inhibitor is 3g/ days.
7. a Bai Ai capsule is preventing and treating the application in hypertension as intestinal transport body inhibitor and irbesartan.
8. application according to claim 6, is characterized in that: the effective dosage ranges of described intestinal transport body inhibitor is 1.5 ~ 6g/ days, and the effective dose of described irbesartan is 120mg/ days.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410645232.2A CN104435312B (en) | 2014-11-12 | 2014-11-12 | A kind of Bai Ai capsules as intestinal transport body inhibitor application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410645232.2A CN104435312B (en) | 2014-11-12 | 2014-11-12 | A kind of Bai Ai capsules as intestinal transport body inhibitor application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104435312A true CN104435312A (en) | 2015-03-25 |
| CN104435312B CN104435312B (en) | 2017-08-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410645232.2A Active CN104435312B (en) | 2014-11-12 | 2014-11-12 | A kind of Bai Ai capsules as intestinal transport body inhibitor application |
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| Country | Link |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1565600A (en) * | 2003-06-30 | 2005-01-19 | 北京中孚天和医药科技有限公司 | Chinese medicinal composition for treating hypertension |
-
2014
- 2014-11-12 CN CN201410645232.2A patent/CN104435312B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1565600A (en) * | 2003-06-30 | 2005-01-19 | 北京中孚天和医药科技有限公司 | Chinese medicinal composition for treating hypertension |
Non-Patent Citations (2)
| Title |
|---|
| 张建萍等: "肠道转运体在药物吸收中的作用", 《中国药学杂志》 * |
| 王京辉等: "血压康胶囊质量标准的研究", 《中国中药杂志》 * |
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| Publication number | Publication date |
|---|---|
| CN104435312B (en) | 2017-08-04 |
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Effective date of registration: 20170704 Address after: 102200 No. 16, life Garden Road, Beijing, Changping District Applicant after: Beijing Haiyan Pharmaceutical Industry Co., Ltd., Yangzijiang Pharmaceutical Ind Applicant after: GUANGDONG ZHONGXI DAYI DRUG DEVELOPMENT CO., LTD. Applicant after: Yangtze River Pharmaceutical Co., Ltd. Address before: 102200 No. 16, life Garden Road, Beijing, Changping District Applicant before: Beijing Haiyan Pharmaceutical Industry Co., Ltd., Yangzijiang Pharmaceutical Ind Applicant before: GUANGDONG ZHONGXI DAYI DRUG DEVELOPMENT CO., LTD. |
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