CN114504572A - Application of parthenolide medicine in preparation of novel medicine for treating rhabdomyosarcoma - Google Patents
Application of parthenolide medicine in preparation of novel medicine for treating rhabdomyosarcoma Download PDFInfo
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- CN114504572A CN114504572A CN202210306793.4A CN202210306793A CN114504572A CN 114504572 A CN114504572 A CN 114504572A CN 202210306793 A CN202210306793 A CN 202210306793A CN 114504572 A CN114504572 A CN 114504572A
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- parthenolide
- medicine
- rhabdomyosarcoma
- drug
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- 201000009410 rhabdomyosarcoma Diseases 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 32
- BUQLXKSONWUQAC-UHFFFAOYSA-N Parthenolide Natural products CC1C2OC(=O)C(=C)C2CCC(=C/CCC1(C)O)C BUQLXKSONWUQAC-UHFFFAOYSA-N 0.000 title claims abstract description 24
- KTEXNACQROZXEV-PVLRGYAZSA-N parthenolide Chemical compound C1CC(/C)=C/CC[C@@]2(C)O[C@@H]2[C@H]2OC(=O)C(=C)[C@@H]21 KTEXNACQROZXEV-PVLRGYAZSA-N 0.000 title claims abstract description 24
- 229940069510 parthenolide Drugs 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title description 4
- 229940079593 drug Drugs 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 4
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 abstract description 2
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 abstract description 2
- 241000196324 Embryophyta Species 0.000 abstract description 2
- 240000004460 Tanacetum coccineum Species 0.000 abstract description 2
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 abstract description 2
- 235000008384 feverfew Nutrition 0.000 abstract description 2
- 229930009674 sesquiterpene lactone Natural products 0.000 abstract description 2
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 5
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000004049 epigenetic modification Effects 0.000 description 1
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229930001431 germacrane Natural products 0.000 description 1
- IBMAYSYTZAVZPY-QDMKHBRRSA-N germacrane Chemical compound CC(C)[C@H]1CC[C@@H](C)CCC[C@@H](C)CC1 IBMAYSYTZAVZPY-QDMKHBRRSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 230000005746 immune checkpoint blockade Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- -1 sesquiterpene compounds Chemical class 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Steroid Compounds (AREA)
Abstract
The invention relates to a novel medicine application of a parthenolide medicine in preparing a medicine for treating rhabdomyosarcoma, wherein the parthenolide is gemmarane type sesquiterpene lactone extracted and separated from plants such as feverfew, and has biological activities of anti-inflammation, antibiosis, tumor resistance and the like.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of a parthenolide medicine in preparation of a novel medicine for treating rhabdomyosarcoma.
Background
Rhabdomyosarcoma (RMS) originates in rhabdomyocytes or mesenchymal cells differentiated to rhabdomyocytes, occurs in about 6 per million worldwide each year, is the most common soft tissue sarcoma in children, and is a very important means in RMS treatment besides extensive excision of R0 cut edges as far as possible. Although the survival of children patients has improved to some extent in the past thirty years, the improvement of treatment quality and the treatment of recurrent RMS still remain a challenge to be solved. With the development of high-throughput sequencing and whole genome sequencing technologies, clues are provided for molecular biological mechanisms affecting RMS and potential targeted molecular therapies, but the specific pathogenesis of RMS is still not fully understood; although targeted drug therapy is currently a focus of research on RMS therapy, few anti-tumor targeted drugs have entered clinical trials. There are several current genomic studies on RMS that show that immune checkpoint blockade and epigenetic modifications can provide more insight to recurrent RMS patients. In addition, serious long-term complications such as delayed development of children may occur in radiotherapy, so that a medicament capable of inhibiting the growth of RMS cells or causing apoptosis of the RMS cells in combination with traditional chemotherapeutic drugs is urgently needed clinically.
Parthenolide (PTL) (structural formula A) is the most representative compound in sesquiterpene compounds, is a germacrane type sesquiterpene lactone extracted and separated from plants such as feverfew, has obvious anti-tumor effect, is nontoxic to normal cells, shows broad-spectrum cytotoxic and apoptosis promoting effects on various tumor cells, and prompts the development prospect of the Parthenolide as an important tumor inhibiting drug. A plurality of researches prove that the PTL has various anti-tumor effects of blocking cell cycle, inhibiting epithelial mesenchymal transition, inhibiting tumor cell migration and invasion, inducing tumor cell apoptosis and autophagy, inhibiting tumor angiogenesis, reversing multidrug resistance and the like, but no report is provided about the application of the parthenolide drug in the preparation of the drug for treating rhabdomyosarcoma at present.
Generally, rhabdomyosarcoma is a highly malignant tumor, and the single treatment effect of rhabdomyosarcoma is poor, and needs comprehensive treatment and long-term follow-up of multiple disciplines such as surgery, chemotherapy, radiotherapy and the like, and the onset thereof can bring heavy economic burden to individuals, families and society of patients, so that finding an effective treatment means for rhabdomyosarcoma becomes one of the problems to be solved urgently in the field of tumor science.
Has the advantages that:
the invention discovers that the application of the parthenolide medicine in preparing the novel medicine for treating rhabdomyosarcoma has the cell proliferation inhibition rate of 97.34 percent and has huge potential application prospect in the treatment of rhabdomyosarcoma.
Disclosure of Invention
It is an object of the present invention to provide a novel pharmaceutical use of a parthenolide drug for the treatment of rhabdomyosarcoma, said method of use comprising administering a therapeutically effective amount of the parthenolide drug to the rhabdomyosarcoma cells (A204).
Further, the invention also relates to a pharmaceutical composition or a pharmaceutical preparation of parthenolide for treating the cancer of rhabdomyosarcoma.
The following examples illustrate the above invention, however, are not intended to limit the scope of the invention in any way. Other test models known to those skilled in the relevant art can also determine the benefits of the claimed invention.
The specific implementation mode is as follows:
the purpose of this experiment was to examine the in vitro cell proliferation inhibitory effect of parthenolide on human rhabdomyosarcoma RD cell line (a 204).
1. Experimental Material
Parthenolide drug was purchased from Nanjing spring and autumn biotechnology, Inc.; human rhabdomyosarcoma A204, purchased from ATCC, USA. Before the experiment, the cells frozen in liquid nitrogen were recovered by a conventional method, and cultured in suspension at 37 ℃ under 5% CO2The high-glucose DMEM medium (supplemented with main components including 10% fetal calf serum, 100U/mL penicillin, 100 mu g/mL streptomycin and 2mmol/L L-glutamine) in the constant-temperature cell culture box is subjected to liquid change and passage once every 2-3 days, and cells in a logarithmic growth phase are taken for experiment.
2. Experimental methods
Tumor cells in logarithmic growth phase are taken, digested by trypsin and resuspended to a cell density of 1.5X 105Cell suspension per mL. The cell suspension was seeded in 96-well culture plates at an inoculum size of 90. mu.L/well, and then 10. mu.L of drug solutions of different concentrations, each concentration being 3 wells, were added to each well. Meanwhile, the medium containing no cells (100. mu.L of medium per well) was set as a blank group, and the cells cultured without drug (10. mu.L of medium in addition to 90. mu.L of cell suspension per well) were set as a control group. After the addition, the 96-well plate was placed at 37 ℃ in 5% CO2The constant temperature cell culture box is used for continuously culturing for 48 hours. After the culture was completed, 10. mu.L of CCK8 reagent was added to each well, and after incubation for 4 hours, the OD450 value of each well was measured in an enzyme-linked immunosorbent assay (the measurement wavelength was 450nm, and the average value of 3 wells was taken), and the proliferation inhibition ratio was calculated according to the following formula:
the proliferation inhibition ratio (%) was [ 1- (OD drug group-OD blank)/(OD control group-OD blank) ] × 100%.
3. Results of the experiment
The results of this experiment are shown below.
| Kind of drug | Drug concentration | Drug proliferation inhibition ratio (%) |
| Doxorubicin (Positive control) | 20μM | 68.06 |
| Parthenolide | 20μM | 97.34 |
From the above table, it can be seen that, the effect of parthenolide on the in vitro cell proliferation of human rhabdomyosarcoma a204 is highly effective, the inhibition rate is as high as 97.34%, and the effect of parthenolide on the proliferation of human rhabdomyosarcoma a204 far exceeds the level of the positive control drug doxorubicin at the same concentration, thus showing that parthenolide has great potential for being developed into drugs for resisting human rhabdomyosarcoma.
In summary, the above experimental results suggest that the parthenolide drug disclosed in the present invention has great application prospect in treating rhabdomyosarcoma and provides more options for means of treating rhabdomyosarcoma in the field.
The embodiments described above represent preferred embodiments of the present invention. It will be apparent to those skilled in the art that various modifications, alterations, substitutions and the like can be made without departing from the spirit and principles of the invention, and these modifications, alterations, substitutions and equivalents should also be construed as falling within the scope of the invention.
Claims (3)
1. An application of parthenolide in preparing a novel medicine for treating rhabdomyosarcoma is provided.
2. The use according to claim 1, wherein the method of pharmaceutical use comprises administering a therapeutically effective amount of a parthenolide drug to rhabdomyosarcoma cells (a 204).
3. Use according to claim 1, wherein the parthenolide drug is in the manufacture of a pharmaceutical composition or a pharmaceutical formulation for the treatment of rhabdomyosarcoma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210306793.4A CN114504572A (en) | 2022-03-25 | 2022-03-25 | Application of parthenolide medicine in preparation of novel medicine for treating rhabdomyosarcoma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210306793.4A CN114504572A (en) | 2022-03-25 | 2022-03-25 | Application of parthenolide medicine in preparation of novel medicine for treating rhabdomyosarcoma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114504572A true CN114504572A (en) | 2022-05-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210306793.4A Pending CN114504572A (en) | 2022-03-25 | 2022-03-25 | Application of parthenolide medicine in preparation of novel medicine for treating rhabdomyosarcoma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114504572A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9314460B1 (en) * | 2013-04-09 | 2016-04-19 | Stc.Unm | Method for cancer cell reprogramming |
-
2022
- 2022-03-25 CN CN202210306793.4A patent/CN114504572A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9314460B1 (en) * | 2013-04-09 | 2016-04-19 | Stc.Unm | Method for cancer cell reprogramming |
Non-Patent Citations (1)
| Title |
|---|
| JOLANTA PARADA-TURSKA等: "Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells" * |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220517 |