CN113648329A - Administration method for zinc oxide nanoparticles to enter brain through gustatory nerve transport - Google Patents
Administration method for zinc oxide nanoparticles to enter brain through gustatory nerve transport Download PDFInfo
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- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 title claims abstract description 120
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 63
- 239000011787 zinc oxide Substances 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims abstract description 25
- 210000004556 brain Anatomy 0.000 title claims abstract description 24
- 210000005036 nerve Anatomy 0.000 title claims abstract description 17
- 230000001339 gustatory effect Effects 0.000 title claims abstract description 14
- 239000000725 suspension Substances 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000008223 sterile water Substances 0.000 claims abstract description 13
- 238000012377 drug delivery Methods 0.000 claims abstract description 8
- 229920000742 Cotton Polymers 0.000 claims abstract description 5
- 239000006185 dispersion Substances 0.000 claims description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 238000005054 agglomeration Methods 0.000 claims description 4
- 230000002776 aggregation Effects 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000009210 therapy by ultrasound Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 20
- 210000004369 blood Anatomy 0.000 abstract description 8
- 239000008280 blood Substances 0.000 abstract description 8
- 238000012546 transfer Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000009885 systemic effect Effects 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- 230000004071 biological effect Effects 0.000 abstract description 3
- 238000010521 absorption reaction Methods 0.000 abstract description 2
- 239000002245 particle Substances 0.000 abstract description 2
- 238000011010 flushing procedure Methods 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 11
- 241000700159 Rattus Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000012795 verification Methods 0.000 description 5
- 210000005013 brain tissue Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- -1 prevention Substances 0.000 description 2
- 238000004506 ultrasonic cleaning Methods 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 206010011985 Decubitus ulcer Diseases 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 210000000959 ear middle Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001932 glossopharyngeal nerve Anatomy 0.000 description 1
- 230000037308 hair color Effects 0.000 description 1
- 230000003803 hair density Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001546 nitrifying effect Effects 0.000 description 1
- 210000000196 olfactory nerve Anatomy 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61K9/10—Dispersions; Emulsions
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a drug delivery method for zinc oxide nano-particles to enter the brain through gustatory nerve transfer, which comprises the steps of preparing zinc oxide nano-particle suspension, dropwise adding the zinc oxide nano-particle suspension on a tongue body according to the weight of the tongue body to enable the zinc oxide nano-particle suspension to be uniformly distributed on the whole tongue body tissue, repeatedly flushing the tongue body with sterile water after the drug delivery is finished, and wiping the tongue body with a sterile cotton swab until the residual zinc oxide nano-particle suspension on the tongue body is completely removed. The zinc oxide nano-particles have excellent rationalization performances such as small particle size, large specific surface area, high biological activity and the like, and can transport the medicine into the brain by using gustatory nerves in a tongue body administration mode. The tongue body tissue has the advantages of large surface area, high absorption speed and the like, and can quickly absorb the medicine; meanwhile, the dripping of the tongue body can effectively remove external interference and reduce the drug transfer to the whole body along with blood. The invention can avoid the systemic action of the medicine, reduce the dosage of the medicine and improve the action efficiency of the medicine.
Description
Technical Field
The invention belongs to the technical fields of biology, medicine, prevention, materials and the like, and relates to a special drug delivery method of zinc oxide nanoparticles, in particular to a drug delivery method targeting into the brain through nerve transport.
Background
The mode of transferring the nano particles into the brain is various, and firstly, the nano particles can be absorbed into blood through intravenous injection, intraperitoneal injection, intragastric perfusion and the like and then enter the brain through blood circulation; secondly, the medicine can enter lymphatic tissues and is transported to the brain through the lymphatic system; thirdly, the medicine is transported into the brain through peripheral nerve by modes of nasal cavity instillation, nasal inhalation, intraocular instillation and the like. The mode of transport of nanoparticles into the brain depends largely on the method of administration. In the existing administration methods, the method for transferring the nerves into the brain has more pertinence and targeting, can use less dosage, can reach the brain area more accurately, reduces the systemic effect of the medicine, and improves the use efficiency of the medicine.
The currently used method of neurotransmission into the brain is mainly through olfactory nerve transport, and then optic nerve and ear nerve, largely depending on the administration method, and there is no administration method related to gustatory nerve.
Disclosure of Invention
The invention aims to overcome the problems and provides a method for administering zinc oxide nanoparticles into the brain through gustatory nerve transport. In order to achieve the purpose, the invention adopts the following technical scheme:
a method for administering zinc oxide nanoparticles into the brain by gustatory nerve transport comprises the following steps:
s1, preparing a zinc oxide nanoparticle suspension;
s2, dropwise adding zinc oxide nanoparticle suspension on the tongue body according to the weight of the tongue body, and enabling the suspension to be uniformly distributed on the whole tongue body tissue;
and S3, after the administration is finished, repeatedly washing the tongue body by using sterile water, and wiping the tongue body by using a sterile cotton swab until the residual zinc oxide nanoparticle suspension on the tongue body is completely removed.
As an improvement, the method for preparing the zinc oxide nanoparticle suspension described in S1 comprises:
s1-1, adding hydroxypropyl methyl cellulose into preheated sterile water, and preparing into dispersion liquid by using a vortex mixer;
s1-2, adding zinc oxide nano-particle powder into the dispersion liquid prepared in the S1 to prepare zinc oxide nano-particle suspension;
s1-3, uniformly mixing by using a vortex mixer, and then carrying out ultrasonic treatment for 30-60min, wherein the vibration frequency is 90 Hz;
and S1-4, repeating the step S1-3 to ensure that the zinc oxide nano particles are uniformly dispersed and have no agglomeration phenomenon.
As an improvement, the mass ratio of the hydroxypropyl methyl cellulose to the sterile water in the step S1-1 is 1: 100.
as a modification, the concentration of the zinc oxide nanoparticle suspension in the S1-2 step is 50 mg/mL.
As a refinement, the dosage of administration in S2 is 5mg per 100g of body weight.
As a refinement, the method of administration is for administration to the brain of an animal.
The invention has the advantages that:
the invention discloses a drug delivery method for transporting a zinc oxide nanoparticle into a brain through gustatory nerve transport, wherein the zinc oxide nanoparticle has excellent rationalization performances such as small particle size, large specific surface area and high biological activity, and can transport a drug into the brain through gustatory nerve by means of tongue body drug delivery.
The tongue body tissue has the advantages of large surface area, high absorption speed and the like, and can quickly absorb the medicine; meanwhile, the dripping of the tongue body can effectively remove external interference and reduce the drug transfer to the whole body along with blood. The invention can avoid the systemic action of the medicine, reduce the dosage of the medicine and improve the action efficiency of the medicine.
Drawings
Figure 1 is a flow chart of a verification test of zinc oxide nanoparticles entering the brain via gustatory nerve transport.
Fig. 2 shows the content of zinc oxide nanoparticles in nervous tissue in the verification test.
Fig. 3 shows the content of zinc oxide nanoparticles in brain tissue in the verification test.
Fig. 4 shows the content of zinc oxide nanoparticles in blood and organs of the whole body in the verification test.
Detailed Description
The present invention will be described in detail and specifically with reference to the following examples so as to facilitate the understanding of the present invention, but the following examples do not limit the scope of the present invention.
Example 1
The embodiment discloses a drug delivery method for zinc oxide nanoparticles to enter the brain through gustatory nerve transport, which comprises the following steps:
s1, preparing a zinc oxide nanoparticle suspension:
s1-1, adding 0.3g of hydroxypropyl methyl cellulose into preheated 30mL of sterile water, and preparing a dispersion by using a vortex mixer;
s1-2, adding zinc oxide nano-particle powder into the dispersion liquid prepared in the S1 to prepare a zinc oxide nano-particle suspension of 50 mg/mL;
s1-3, uniformly mixing by using a vortex mixer, and then carrying out ultrasonic treatment for 30-60min, wherein the vibration frequency is 90 Hz;
and S1-4, repeating the step S1-3 to ensure that the zinc oxide nano particles are uniformly dispersed and have no agglomeration phenomenon.
S2, dropwise adding zinc oxide nanoparticle suspension on the tongue body according to the weight of the tongue body, and enabling the suspension to be uniformly distributed on the whole tongue body tissue, wherein the administration dose is 5mg per 100g of the weight.
And S3, after the administration is finished, repeatedly washing the tongue body by using sterile water, and wiping the tongue body by using a sterile cotton swab until the residual zinc oxide nanoparticle suspension on the tongue body is completely removed.
The invention carried out a verification test on the scheme of example 1
1. Animal selection
20 adult male Wistar rats with the weight of 120-150g were purchased from the southern medical university animal center and randomly divided into two groups, wherein the experimental group comprises a zinc oxide nanoparticle group and a control group of sterile water, and each group comprises 10 rats, and the rats are required to be healthy, normal in activity and normal in hair color and density. The experimental animals are raised in an SPF animal room of an animal experiment center of southern medical university, the indoor temperature is 23 +/-1 ℃, and the relative humidity is 55-65%.
2. Preparation of zinc oxide nanoparticles
0.3g of hydroxypropylmethylcellulose was weighed with an electronic analytical balance, added to 30mL of preheated sterile water, and prepared into a dispersion with a vortex mixer.
1.5g of zinc oxide nanoparticle powder was weighed using an electronic analytical balance, and added to a 100mL serum bottle containing 30mL of the dispersion to prepare a zinc oxide nanoparticle suspension having a concentration of 50mg/mL, and the bottle cap was marked with "zinc oxide nanoparticle suspension" using label paper.
Vigorously blending with a vortex mixer. Then, the zinc oxide nanoparticle suspension is subjected to ultrasound for 30-60min by an ultrasonic cleaning machine, and the vibration frequency is 90 Hz. And then vigorously mixing by using a vortex mixer. And (3) carrying out ultrasonic treatment for 30-60min by using an ultrasonic cleaning machine to uniformly disperse the zinc oxide nano particles until no macroscopic agglomeration phenomenon exists.
3. Method of administration
Weighing the daily weight of each rat by using an electronic balance, making a record, calculating the anesthetic amount and the zinc oxide nanoparticle suspension amount of each rat according to the weight, and observing whether the activity state of the rat is normal or not.
Then, according to the dose of 0.48mL/100g, the concentration of 1% sodium pentobarbital is injected into the abdominal cavity, the anesthesia onset time is 3-10min, and the duration time is about 2-3 h.
The anesthetized rat was placed on the operating table in the lateral decubitus position, and the tongue tissue was gently pulled out from the lateral corner of the mouth with the elbow forceps.
The experimental group adopts a micro-injector, and 5mg/100g zinc oxide nanoparticle suspension is dropwise added on the tongue body according to the weight of the animal, so that the suspension is uniformly distributed on the whole tongue body tissue.
After about 2 hours of administration, the residual suspension of zinc oxide nanoparticles on the tongue body is repeatedly washed with sterile water and wiped with a sterile cotton swab until the residual suspension of zinc oxide nanoparticles on the tongue body is completely removed, so that the residual zinc oxide nanoparticles on the tongue body tissue are prevented from entering the stomach through the esophagus and entering the brain through a blood circulation mode.
The control group was added with 5mg/100g of sterile water in equal amounts by a micro syringe. After completion of the procedure, the rats were waited for resuscitation.
The administration time is 1, 3, 5, 7 … … 27, 29d, the administration is carried out every other day, and the tissue detection is extracted after 30d anesthesia.
4. Biological assays
The tympanum, glossopharyngeal nerve, brain tissue, blood and whole body viscera of the rats of the experimental group and the control group are respectively extracted, different surgical instruments are adopted in the operation, and the cross contamination is avoided.
And weighing the collected samples to be detected by using an electronic analytical balance, and respectively weighing 0.2g for detection. Respectively adding the samples to be detected into a polytetrafluoroethylene digestion tank containing concentrated nitric acid, and nitrifying overnight. Then 0.5mL of hydrogen peroxide solution was added to the digestion tank and heated at 160 ℃ under high pressure until the tissue was completely digested. And continuously heating the mixed solution at 120 ℃ until the nitric acid is completely evaporated, cooling the sample, transferring the sample into a 5mL colorimetric tube, fixing the volume to 5mL by using deionized water, centrifuging, collecting supernatant, detecting the content of zinc in each sample by adopting ICP-MS (inductively coupled plasma-mass spectrometry), and uniformly converting the content into the content of zinc oxide nano particles for comparison.
5. Conclusion of the experiment
As can be seen from fig. 2 and 3, the experimental group and the control group had more zinc oxide nanoparticles in both the nerve tissue and the brain tissue. The zinc oxide nano-particles have better biological activity and can carry out drug transport through nervous tissues. Comparing the experimental group with the control group, the content of the experimental group after suspension treatment in the nervous tissue and the brain tissue is obviously higher than that of the control group, which shows that the suspension treatment can effectively increase the transfer effect and the transfer efficiency of the zinc oxide nano particles.
Comparing the control group and the experimental group in fig. 4, the contents of the zinc oxide nanoparticles in blood, heart, liver, spleen, lung and kidney were not statistically different, considering that the blood and the internal organs of the human body contain zinc. Therefore, it can be proved that the zinc oxide nanoparticles are transported into the brain only through gustatory nerve transport after being instilled in the tongue, and do not follow the blood to perform systemic circulation. The proposal has pertinence and targeting property, can avoid the systemic action of the medicine and improve the action efficiency of the medicine.
The embodiments of the present invention have been described in detail above, but they are merely exemplary, and the present invention is not equivalent to the above described embodiments. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, it is intended that all equivalent alterations and modifications be included within the scope of the invention, without departing from the spirit and scope of the invention.
Claims (6)
1. A drug delivery method of zinc oxide nanoparticles transported into the brain through gustatory nerve is characterized by comprising the following steps:
s1, preparing a zinc oxide nanoparticle suspension;
s2, dropwise adding zinc oxide nanoparticle suspension on the tongue body according to the weight of the tongue body, and enabling the suspension to be uniformly distributed on the whole tongue body tissue;
and S3, after the administration is finished, repeatedly washing the tongue body by using sterile water, and wiping the tongue body by using a sterile cotton swab until the residual zinc oxide nanoparticle suspension on the tongue body is completely removed.
2. The method of claim 1, wherein the step of formulating the suspension of zinc oxide nanoparticles comprises:
s1-1, adding hydroxypropyl methyl cellulose into preheated sterile water, and preparing into dispersion liquid by using a vortex mixer;
s1-2, adding zinc oxide nano-particle powder into the dispersion liquid prepared in the S1 to prepare zinc oxide nano-particle suspension;
s1-3, uniformly mixing by using a vortex mixer, and then carrying out ultrasonic treatment for 30-60min, wherein the vibration frequency is 90 Hz;
and S1-4, repeating the step S1-3 to ensure that the zinc oxide nano particles are uniformly dispersed and have no agglomeration phenomenon.
3. The method of claim 2, wherein the mass ratio of hydroxypropyl methylcellulose to sterile water in step S1-1 is 1: 100.
4. the method of claim 2, wherein the suspension of zinc oxide nanoparticles in S1-2 has a concentration of 50 mg/mL.
5. The method of claim 1 or 4, wherein the amount of S2 administered is 5mg per 100g of body weight.
6. The method of claim 1, wherein the zinc oxide nanoparticles are administered to the brain via gustatory nerve transport.
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Citations (4)
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|---|---|---|---|---|
| CN105017566A (en) * | 2014-04-28 | 2015-11-04 | 海南光宇生物科技有限公司 | HPMC (hydroxy propyl methyl cellulose) composite film containing biologic cellulose and zinc oxide nanometer particles |
| CN105707004A (en) * | 2016-01-26 | 2016-06-29 | 浙江省中医院 | Building method of mouse liver apoptosis animal model induced by nanometer zinc oxide |
| CN110269040A (en) * | 2019-05-28 | 2019-09-24 | 军事科学院军事医学研究院环境医学与作业医学研究所 | A kind of method for building up of particulate matter breath exposure neurotoxicity rat model |
| CN111821508A (en) * | 2020-07-15 | 2020-10-27 | 南方医科大学口腔医院 | Composite freezing gel and preparation method and application thereof |
-
2021
- 2021-08-20 CN CN202110961075.6A patent/CN113648329A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017566A (en) * | 2014-04-28 | 2015-11-04 | 海南光宇生物科技有限公司 | HPMC (hydroxy propyl methyl cellulose) composite film containing biologic cellulose and zinc oxide nanometer particles |
| CN105707004A (en) * | 2016-01-26 | 2016-06-29 | 浙江省中医院 | Building method of mouse liver apoptosis animal model induced by nanometer zinc oxide |
| CN110269040A (en) * | 2019-05-28 | 2019-09-24 | 军事科学院军事医学研究院环境医学与作业医学研究所 | A kind of method for building up of particulate matter breath exposure neurotoxicity rat model |
| CN111821508A (en) * | 2020-07-15 | 2020-10-27 | 南方医科大学口腔医院 | Composite freezing gel and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
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| 陈艾婕: "经味觉通路的纳米氧化锌和纳米二氧化钛颗粒的中枢神经毒性", 《中国优秀博硕士学位论文全文数据库(硕士) 医药卫生科技辑》 * |
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