CN115282139A - Use of 1,5-AG for preparing medicine for treating acute kidney injury - Google Patents
Use of 1,5-AG for preparing medicine for treating acute kidney injury Download PDFInfo
- Publication number
- CN115282139A CN115282139A CN202211075317.2A CN202211075317A CN115282139A CN 115282139 A CN115282139 A CN 115282139A CN 202211075317 A CN202211075317 A CN 202211075317A CN 115282139 A CN115282139 A CN 115282139A
- Authority
- CN
- China
- Prior art keywords
- kidney injury
- acute kidney
- treating acute
- kidney
- pharmaceutically acceptable
- 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.)
- Pending
Links
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 30
- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 28
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 28
- MPCAJMNYNOGXPB-SLPGGIOYSA-N 1,5-anhydro-D-glucitol Chemical compound OC[C@H]1OC[C@H](O)[C@@H](O)[C@@H]1O MPCAJMNYNOGXPB-SLPGGIOYSA-N 0.000 title claims abstract description 25
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000012439 solid excipient Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 230000003907 kidney function Effects 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 230000007423 decrease Effects 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 208000012998 acute renal failure Diseases 0.000 abstract description 2
- 230000006870 function Effects 0.000 abstract description 2
- 208000017169 kidney disease Diseases 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract description 2
- 210000003734 kidney Anatomy 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 210000005084 renal tissue Anatomy 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000742679 Coprosma repens Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 210000000738 kidney tubule Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses application of 1,5-AG in preparing a medicament for treating acute kidney injury. Acute kidney injury is one of the more common clinical renal diseases, the renal function rapidly decreases when the disease occurs, and the progress of the disease process finally leads to acute renal failure and the function decrease of other organs of the body. The invention discovers that 1,5-AG has obvious treatment effect on acute kidney injury, so the invention has application prospect in developing drugs for treating acute kidney injury.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of 1,5-AG in preparation of a medicine for treating acute kidney injury.
Background
Acute Kidney Injury (AKI) is one of the more common clinical renal diseases, and renal function rapidly decreases at the onset of the disease, and the progress of the disease finally leads to acute renal failure and the reduction of functions of other organs of the body. The occurrence of ischemia reperfusion, the application of anti-tumor drugs, rhabdomyolysis, bacterial infection and even improper administration can all cause the occurrence.
1,5-anhydroglucitol (abbreviation: 1,5-AG, chinese name: 1, 5-anhydroglucitol) is an important index for diagnosis of diabetes, and is currently commonly used for diagnosis of diabetes. No 1,5-AG treatment of acute kidney injury has been reported.
Disclosure of Invention
The invention aims to provide application of 1,5-AG in preparing a medicament for treating acute kidney injury.
The above purpose of the invention is realized by the following technical scheme:
use of 1,5-anhydroglucitol for the preparation of a medicament for the treatment of acute kidney injury.
Furthermore, the medicine takes 1,5-anhydroglucitol as an active ingredient and is prepared into a pharmaceutically acceptable dosage form by pharmaceutically acceptable auxiliary materials.
Further, the pharmaceutically acceptable excipients are solid, liquid or semisolid excipients.
Further, the pharmaceutically acceptable dosage forms include tablets, capsules, pills, oral liquids and powders.
Has the advantages that:
the invention discovers that 1,5-AG has obvious treatment effect on acute kidney injury, so the invention has application prospect in the development of medicines for treating acute kidney injury.
Drawings
FIG. 1 shows the serum urea nitrogen (BUN) and creatinine (Scr) contents of mice.
FIG. 2 shows the results of H & E staining and scoring thereof.
Detailed Description
The following examples are given to illustrate the essence of the present invention, but not to limit the scope of the present invention.
1. Experimental Material
1,5-anhydroglucitol (Sigma, A7165-100 MG); SPF-grade ICR mice were purchased from the Qinglongshan animal breeding farm in Jiangning district, nanjing (quality certification number: 201926974).
Paraformaldehyde (shinyleaf fine chemical research institute of Tianjin), xylene (chemical reagents of national drug group Co., ltd.), H & E dye liquor (Beijing Solaibao biology), and neutral gum (chemical reagents of national drug group Co., ltd.).
2. Experimental method
1. Animal grouping, modeling and administration
ICR mice were acclimatized for one week and then randomly divided into three groups of 6 mice each, namely a control group (Sham), a model group (AKI) and a dosing group (AKI +1, 5-AG). The model group and the administration group are subjected to bilateral renal ischemia reperfusion surgery for acute renal injury modeling, and the surgery process is as follows: after the mice are anesthetized, the prone position is placed on a foam plate, the specific position of the kidney is positioned before the skin is covered, then the inner skin is cut open, the kidney is slightly extruded by hand, and the adipose tissues around the kidney are separated pelagically by using bent forceps. The arteriovenous clamp at the renal pelvis position of the kidney is then fully occluded using an elbow arterial clamp. The successful occlusion was indicated by the immediate reddish change of the kidney to purplish black (during ischemia the kidney was covered with saline-soaked gauze to keep the kidney moist throughout), and 45min after ischemia the arterial clamp was released. Successful reperfusion is indicated by rapid change of the kidney from purple-black to bright red. The kidneys were then gently returned to the body with hands and curved forceps and the inner cortex sutured closed. One-sided surgery is completed. The other side was operated again in the same manner. During the whole experiment process, the mouse is placed on the heating blanket, so that the body temperature of the mouse is always kept at 37 ℃, and the recovery after the experiment is facilitated. The control group caused only the operative wound without clamping the artery and vein (Sham), wherein the administration group started to administer 1,5-AG before 3 days before the operation, the intraperitoneal injection administration was continued for 1 day of 1,5-AG after the operation, the daily dose was 100mg/kg, and the control group and the model group were administered with the same amount of vehicle each day.
2. Animal sacrifice, sampling and sample handling
After 1,5-AG 1 day after surgery, whole blood was collected from the eye, and the mice were dissected to remove kidney tissue. Centrifuging whole blood at 3000rpm and 4 deg.C for 10min, sucking supernatant clear serum liquid, transferring to a sterile centrifuge tube for biochemical index detection, and placing the rest in-80 deg.C refrigerator for use; rapidly picking kidney tissue, washing in normal saline, removing surface adipose tissue and mucosa, and fixing 1/3 of kidney tissue in 4% paraformaldehyde for histopathological examination.
3. Serum biochemical and histopathological detection
3.1 Biochemical detection of serum
The full-automatic biochemical analyzer is automatically detected by the instrument after sample loading, the sample concentration is automatically generated by the instrument according to an index result, and then the excel is exported; operating according to the kit specification according to biochemistry, converting the measured absorbance of the sample into concentration according to the formula in the specification, using GraphPad software to make a histogram, and performing statistical test.
3.2 tissue sections and H & E staining
And (4) dehydrating the fixed kidney tissues, and embedding and slicing the dehydrated kidney tissues by paraffin.
H & E staining: sequentially placing the slices into xylene I20 min, xylene II 20min, anhydrous ethanol I5 min, anhydrous ethanol II 5min, and 75% ethanol 5min, and washing with tap water; staining the slices in hematoxylin staining solution for 3-5min, washing with tap water, differentiating the differentiation solution, washing with tap water, returning blue to the blue solution, and washing with running water; the slices are dehydrated for 5min respectively by adding 85 percent and 95 percent gradient alcohol in sequence, and are dyed for 5min in eosin dye solution; placing the slices in anhydrous alcohol I for 5min, anhydrous alcohol II for 5min, anhydrous alcohol III for 5min, xylene I for 5min, and xylene II for 5min, and sealing with neutral gum.
3.3 microscopic examination and image acquisition and analysis
The pathological section is evaluated and scored after microscopic examination, and representative images are taken.
5. Data processing and statistical analysis
Student's test, () p <0.05, () p <0.01, () p <0.001 was used.
3. Results of the experiment
1. Effect of 1,5-AG on serum biochemistry of AKI model mice
The results are shown in fig. 1, and compared with the control group (Sham), the serum urea nitrogen (BUN) and the creatinine (Scr) of the model group (AKI) mice are obviously increased, which indicates that the kidney function is abnormal, and the model building of the AKI model is successful; the two indexes are obviously reduced after 1 day of 1,5-AG postoperative administration, show the protective effect of 1,5-AG on kidney function, and play a role in treating acute kidney injury model mice.
2. 1,5-AG protective Effect on kidney of AKI model mouse
As can be seen from the H & E staining results in FIG. 2, the kidney tubules in the kidney tissue of the model group (AKI) mice were moderately atrophied, the tubular cavity was enlarged, the local inflammation was evident, and the epithelial cells were necrotic or denatured, as compared with the control group (Sham); the stroma has obvious inflammatory cell infiltration, which indicates that the kidney function is abnormal, and the AKI model is successfully modeled. 1,5-AG can obviously improve the pathological changes after being administrated, the atrophy and the cavity expansion degree of renal tubules are obviously reduced compared with a model group, epithelium is only slightly necrotic, and mild inflammatory cell infiltration is realized, so that the 1,5-AG has the protection effect on renal function and has a treatment effect on acute renal injury model mice.
The results show that the 1,5-AG has obvious treatment effect on acute kidney injury, so that the application prospect of developing the medicament for treating the acute kidney injury is realized.
The above-described embodiments are intended to be illustrative of the nature of the invention, but those skilled in the art will recognize that the scope of the invention is not limited to the specific embodiments.
Claims (4)
1.1, use of 5-anhydroglucitol for preparing a medicament for treating acute kidney injury.
2. The use of claim 1, wherein the medicament comprises 1,5-anhydroglucitol as an active ingredient and pharmaceutically acceptable excipients to prepare pharmaceutically acceptable dosage forms.
3. The use according to claim 2, wherein the pharmaceutically acceptable excipient is a solid, liquid or semi-solid excipient.
4. The use of claim 2, wherein the pharmaceutically acceptable dosage forms comprise tablets, capsules, pills, oral liquids, and powders.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211075317.2A CN115282139A (en) | 2022-09-04 | 2022-09-04 | Use of 1,5-AG for preparing medicine for treating acute kidney injury |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211075317.2A CN115282139A (en) | 2022-09-04 | 2022-09-04 | Use of 1,5-AG for preparing medicine for treating acute kidney injury |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115282139A true CN115282139A (en) | 2022-11-04 |
Family
ID=83831746
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211075317.2A Pending CN115282139A (en) | 2022-09-04 | 2022-09-04 | Use of 1,5-AG for preparing medicine for treating acute kidney injury |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115282139A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022059694A1 (en) * | 2020-09-16 | 2022-03-24 | 国立大学法人鹿児島大学 | Composition for improving renal function |
-
2022
- 2022-09-04 CN CN202211075317.2A patent/CN115282139A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022059694A1 (en) * | 2020-09-16 | 2022-03-24 | 国立大学法人鹿児島大学 | Composition for improving renal function |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113041312A (en) | Traditional Chinese medicine composition for treating premature ovarian failure and preparation method and application thereof | |
| CN109966434B (en) | Traditional Chinese medicine composition, traditional Chinese medicine compound preparation, and preparation method and application thereof | |
| CN115282139A (en) | Use of 1,5-AG for preparing medicine for treating acute kidney injury | |
| CN114984028B (en) | Application of astragaloside IV | |
| CN108434166B (en) | Pharmaceutical composition for treating thromboembolism, preparation method, preparation and application thereof | |
| CN104161850B (en) | The preparation method of a kind of Chinese medicine extract and the Chinese medicine extract of preparation thereof and purposes | |
| CN115025137A (en) | External traditional Chinese medicine extract for promoting wound healing and extraction method and application thereof | |
| CN114869952A (en) | Application of cortex lycii radicis extract in preparation of product for repairing reproductive system injury | |
| CN111920905B (en) | Traditional Chinese medicine composition and application thereof | |
| CN115463142A (en) | Application of naringin dihydrochalcone in preparation of medicine for treating pulmonary fibrosis | |
| CN114796195A (en) | Application of icaritin in preparation of pharmaceutical composition for protecting acute lung injury induced by lipopolysaccharide | |
| CN113041336A (en) | Traditional Chinese medicine composition for treating premature ovarian failure and preparation method and application thereof | |
| CN109512962B (en) | Traditional Chinese medicine composition for organ fibrosis and preparation method and application thereof | |
| CN111568937A (en) | Application of pien Tze Huang and preparation thereof in preparation of medicine for promoting healing of refractory wound | |
| CN102327360A (en) | Gel preparation for treating cervical erosion and preparation method thereof | |
| CN109470788A (en) | A kind of method of quality control of FUKE QIANJIN PIAN | |
| CN109364148A (en) | A kind of FUKE QIANJIN PIAN and preparation method thereof | |
| CN115607610B (en) | Traditional Chinese medicine composition for treating abnormal glycolipid metabolism and/or intestinal flora imbalance as well as preparation method and application thereof | |
| CN108653401A (en) | A kind of compound medicinal formulation and preparation method thereof for treating ulcerative colitis | |
| CN113456723B (en) | Pharmaceutical composition and use thereof | |
| CN116370548B (en) | Traditional Chinese medicine composition with effect of improving polycystic ovarian syndrome and preparation method and application thereof | |
| WO2023174205A1 (en) | Pharmaceutical formulation and use thereof | |
| CN107050359A (en) | Treat strong medicine preparation of chronic pelvic inflammatory disease sequelae and preparation method thereof | |
| CN116966219A (en) | Charcoal medicine with effect of inhibiting kidney injury caused by aristolochic acid | |
| CN113876792A (en) | Medical application of ginsenoside Rg5 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20221104 |
|
| WD01 | Invention patent application deemed withdrawn after publication |