CN104622848A - Plasma activation encapsulated micro-bubbles - Google Patents

Plasma activation encapsulated micro-bubbles Download PDF

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Publication number
CN104622848A
CN104622848A CN201510079371.8A CN201510079371A CN104622848A CN 104622848 A CN104622848 A CN 104622848A CN 201510079371 A CN201510079371 A CN 201510079371A CN 104622848 A CN104622848 A CN 104622848A
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China
Prior art keywords
peplos
microbubble
plasma
bubbles
particle
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CN201510079371.8A
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Chinese (zh)
Inventor
刘定新
刘志超
陈晨
孔刚玉
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Xian Jiaotong University
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Xian Jiaotong University
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Priority to CN201510079371.8A priority Critical patent/CN104622848A/en
Publication of CN104622848A publication Critical patent/CN104622848A/en
Pending legal-status Critical Current

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Abstract

The invention discloses plasma activation encapsulated micro-bubbles. The plasma activation encapsulated micro-bubbles are characterized by comprising an encapsulating film, substances in the film, and additive substances which are adhered to the encapsulating film or are wrapped in the encapsulating film and are applied to targeted positioning, wherein a film material of the encapsulating film is protein, lipid, a surfactant or a polymer; and the substances in the film comprise inert gas and active particles produced by plasma. Because the film material cannot react with the active particles and is isolated from the external environment, the service life of the active particles in a micro-environment of the micro-bubbles can be greatly prolonged, and a concentration proportion relationship among the active particles can be maintained; after the encapsulated micro-bubbles are adhered with specific protein or are wrapped by targeted positioning substances such as nano-ferromagnetic materials, the encapsulated micro-bubbles can be aggregated at a specific position, and then the encapsulated micro-bubbles are broken under the control of ultrasonic waves to release the active particles in the encapsulated micro-bubbles. The plasma activation encapsulated micro-bubbles disclosed by the invention can be used for greatly increasing the penetration depth of the active particles, and also have targeted positioning functions.

Description

A kind of plasma-activated peplos microbubble
Technical field
The present invention relates to plasma field of medical applications, particularly the plasma-activated peplos microbubble of one.
Background technology
Research find the gas-phase activity particle that plasma produces or with water effect after the liquid phase active particle that generates, as O 2, HO 2, HO 3, O 3, OH, H 2o 2, ONOOH and NO, can perform well in treatment dermatosis, kill cancerous cell and pathogenic microorganism, there is important medical application.But some is as O 2, the short life active particle such as OH, ONOOH, because its chemical property is active, is difficult to penetrate in body fluid arrive in deep tissues and treats.There are some researches show, the effect of various active particle cooperative has more value than single active particle, but in process of osmosis between active particle concentration ratio change synergy can be made to lose.These two aspects factor all governs plasma for medical domain.
Summary of the invention
Given this, the invention discloses a kind of plasma-activated peplos microbubble, it is characterized in that: described peplos microbubble comprises material in peplos and film, the membrane material of described peplos is protein, lipid, surfactant or polymer; In described film, material comprises the active particle of noble gas and plasma generation; Described peplos microbubble also comprises the added substance for targeting location being attached on peplos or being wrapped in peplos.
Accompanying drawing explanation
Fig. 1 is the gaseous active particle of parcel plasma generation shown in one embodiment of the present of invention and the peplos microbubble of nanoscale ferromagnetic particle.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further illustrated.
For the present invention, most basic embodiment is to propose a kind of plasma-activated peplos microbubble, and it is characterized in that: described peplos microbubble comprises material in peplos and film, the membrane material of described peplos is protein, lipid, surfactant or polymer; In described film, material comprises the active particle of noble gas and plasma generation; Described peplos microbubble also comprises the added substance for targeting location being attached on peplos or being wrapped in peplos.
With regard to above-described embodiment, described peplos microbubble can improve the permeability of material in film, and can carry targeting location material, is convenient to the targeting application in later stage application.Be attached on peplos, can by the mode such as inlaying.Because membrane material can be accomplished not react with active particle and isolated external environment condition, considerably increase the life-span of active particle in the microenvironment therefore in microbubble, thus the concentration proportioning relation between active particle can be maintained.If after peplos microbubble attachment specific proteins or this kind of targeting of parcel nanometer ferromagnetic material locate material, can assemble at ad-hoc location.Preferred, if recycling ultrasound wave controls the active particle breaking to discharge inside of peplos microbubble.The present invention can increase substantially the length of penetration of active particle, and has the function of targeting location further.
The preparation of described peplos microbubble, choosing multiple method.Such as, the peplos microbubble of available sonic-vacating method preparation parcel Plasma gas active particle and nanoscale ferromagnetic particle, as Fig. 1.Membrane material can be protein, lipid, surfactant or polymer.Pour in container by the membrane material solution of mix homogeneously and ferromagnetic particle solution, sound Vibration Meter probe inserts below liquid level, while the work of sound Vibration Meter, at the container bottom at the uniform velocity gaseous active particle that produces of injected plasma.The producing method of plasma can be other modes such as creeping discharge, dielectric barrier discharge, jet and discharge in water.Preparation terminates rear centrifugal mixed solution, is separated peplos microbubble.The peplos microbubble preparation method of the liquid reactive particle that parcel plasma and water effect produce is similar.Widely, described plasma-activated peplos microbubble, utilizes acoustic cavitation or lyophilization or sprays or emulsion, or the preparation of ink-jet blot format.
Preferably, aqueous solution plasma treatment crossed mixes with membrane material solution to be poured in container, and container bottom at the uniform velocity passes into noble gas, produces peplos microbubble under the effect of sound Vibration Meter.
Peplos microbubble wrap up gaseous active particle that plasma produces or with water effect after the liquid reactive particle that generates, can be convenient to along with peplos microbubble inject in Symptomatic animal body in later stage application.If parcel ferromagnetic particle, just easily arrives target location under the guiding of externally-applied magnetic field in peplos microbubble.If ultrasound wave is aimed at lesions position, make the peplos microbubbles rupture with lesion tissue specific binding, wherein active particle just can penetrate in histiocyte under hyperacoustic effect.That is, microbubble of the present invention can be used for entering lesion tissue and treating disease.
Peplos microbubble is a kind of novel product, can be widely used in targeting application and the tissue contrast of medicine or gene.It is the bubble formation of the micro-meter scale being wrapped up micron level by protein, lipid, surfactant or polymer.Medicine or contrast agent etc. can be attached to or be inlaid on peplos, also can be wrapped in peplos.When for some special applications, can modify its shell surface peplos microbubble, as increased antibody, part or contrast agent component etc.The bubble of the micro-meter scale size that described microbubble comprises can be helium bubble, argon gas bubbles or other rare gas bubbles; Along with further developing of technology, this bubble scale can from micro-meter scale toward more small scale transition.
As previously mentioned, microbubble of the present invention can utilize the various ways preparations such as acoustic cavitation, lyophilization, spraying, emulsion, ink-jet trace.The film that microbubble is formed by protein, lipid, surfactant or polymer membrane material wrapped up.This film membrane material used can be accomplished animal (comprising the mankind) harmless as lapping, and not with activity characteristic particle reaction.Preferred, the structure of microbubble can be single or multiple lift package structure, the gaseous active particle that parcel plasma produces: when described peplos microbubble is single layer structure, the liquid reactive particle produced after the gaseous active particle that internal package plasma produces or plasma and water effect.When described peplos microbubble is double-decker, the liquid reactive particle that internal layer produces after wrapping up plasma and water effect, and then wrap up noble gas.These active particles include but not limited to as O 2, HO 2, HO 3, O 3, OH, H 2o 2, ONOOH, NO and other active ion.
Add antibody or part at the putamina of peplos microbubble, specific binding can be carried out with pathogen in animal body.Or in putamina, add nanoscale ferromagnetic particle, utilize external magnetic field to guide and make it be gathered in lesions position.In the application, inject after in Symptomatic animal body, ultrasound wave can be adopted to control peplos microbubbles rupture.Hyperacoustic energy can impel active particle to penetrate in tissue, simultaneously the absorption of the mobility promotion cell that can increase cell membrane that breaks of microbubble film.
To carry medicine, because peplos microbubble average diameter can accomplish to be less than erythrocyte, tiny blood capillary can be penetrated into, and discharge medicine under ul-trasonic irradiation, the active particle that therefore peplos microbubble parcel plasma produces effectively can solve the problem that active particle enters lesion tissue difficulty.In addition, active particle is wrapped in and is hedged off from the outer world by the film that inert material is formed, and substantially increases the life-span.The antibody on peplos microbubble surface or part can carry out specific binding with treat target tissue, make active particle directly act on destination organization.Add nanoscale ferromagnetic particle in this external putamina, utilize external magnetic field to guide, microbubble can be introduced lesion tissue, realize targeted therapy.Microbubble of the present invention can increase substantially the length of penetration of active particle, and can be used in targeting location.
Owing to have employed technique scheme, solve gas-phase activity particle that plasma produces or with water effect after the liquid phase active particle that produces be difficult to penetrate into the problem of deep tissues, make active particle can targetedly, reliably, target approach position efficiently.
Above to the present invention, be described in detail, apply specific case herein and set forth principle of the present invention and embodiment, the explanation of above embodiment just understands method of the present invention and core concept thereof for helping; Meanwhile, for one technical staff of this area, according to thought of the present invention, all will change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.

Claims (7)

1. a plasma-activated peplos microbubble, is characterized in that: described peplos microbubble comprises material in peplos and film, and the membrane material of described peplos is protein, lipid, surfactant or polymer; In described film, material comprises the active particle of noble gas and plasma generation; Described peplos microbubble also comprises the added substance for targeting location being attached on peplos or being wrapped in peplos.
2. peplos microbubble according to claim 1, is characterized in that: preferred, can add nanoscale ferromagnetic particle, for the bootstrapping collection at external magnetic field in target location in described peplos; Or add antibody or the part with function of specific connecting at described peplos outer surface, make peplos microbubble automatically be gathered in target location.
3. peplos microbubble according to claim 1, is characterized in that: described microbubble comprises the helium bubble of micro-meter scale size, argon gas bubbles or other rare gas bubbles.
4. peplos microbubble according to claim 1, is characterized in that: described plasma-activated peplos microbubble, by acoustic cavitation or lyophilization or spraying or emulsion, or the preparation of ink-jet blot format.
5. peplos microbubble according to claim 1, is characterized in that: described active particle is gaseous matter or liquid substance; When for gaseous matter, described gaseous matter is the gaseous active particle that plasma produces; When for liquid substance, described liquid substance is the liquid reactive particle produced after plasma and water effect.
6. peplos microbubble according to claim 5, is characterized in that: described peplos microbubble is monolayer or double-decker; When described peplos microbubble is single layer structure, the liquid reactive particle produced after the gaseous active particle that internal package plasma produces or plasma and water effect; When described peplos microbubble is double-decker, the liquid reactive particle that internal layer produces after wrapping up plasma and water effect, and then wrap up one deck noble gas.
7., according to the arbitrary described peplos microbubble of claim 5,6, it is characterized in that: when peplos microbubble gathers target location, adopt ultrasound wave to control breaking of peplos microbubble.
CN201510079371.8A 2015-02-13 2015-02-13 Plasma activation encapsulated micro-bubbles Pending CN104622848A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110575551A (en) * 2018-06-08 2019-12-17 北京大学 ultrasonic contrast agent and preparation method thereof
CN111729092A (en) * 2020-06-28 2020-10-02 南京超维景生物科技有限公司 Magnetic ultrasonic contrast agent composition, magnetic ultrasonic contrast agent, magnetic microbubble ultrasonic contrast agent and preparation method thereof
CN114210970A (en) * 2021-12-28 2022-03-22 北京建工环境修复股份有限公司 Coated iron-carbon composite material, preparation and modification methods thereof and sewage treatment method

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CN1559615A (en) * 2004-02-25 2005-01-05 王志刚 Location controlled releasing method for ultrasonic microbubble contrast medium
CN1744921A (en) * 2003-02-04 2006-03-08 伯拉考国际股份公司 Ultrasound contrast agents and process for the preparation thereof
CN102772808A (en) * 2012-07-02 2012-11-14 重庆医科大学 Multi-modality imaging microbubble structure, preparation method and applications
CN103202776A (en) * 2013-01-21 2013-07-17 北京大学 Preparation method for mouthwash based on low temperature plasma
CN103638534A (en) * 2013-12-02 2014-03-19 东南大学 Nanometer lipid ultrasonic contrast agent and preparation method thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1141001A (en) * 1994-12-16 1997-01-22 勃勒柯研究有限公司 Method of storage of ultrasonic gas suspensions
CN1744921A (en) * 2003-02-04 2006-03-08 伯拉考国际股份公司 Ultrasound contrast agents and process for the preparation thereof
CN1559615A (en) * 2004-02-25 2005-01-05 王志刚 Location controlled releasing method for ultrasonic microbubble contrast medium
CN102772808A (en) * 2012-07-02 2012-11-14 重庆医科大学 Multi-modality imaging microbubble structure, preparation method and applications
CN103202776A (en) * 2013-01-21 2013-07-17 北京大学 Preparation method for mouthwash based on low temperature plasma
CN103638534A (en) * 2013-12-02 2014-03-19 东南大学 Nanometer lipid ultrasonic contrast agent and preparation method thereof

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110575551A (en) * 2018-06-08 2019-12-17 北京大学 ultrasonic contrast agent and preparation method thereof
CN110575551B (en) * 2018-06-08 2020-11-03 北京大学 Ultrasonic contrast agent and preparation method thereof
CN111729092A (en) * 2020-06-28 2020-10-02 南京超维景生物科技有限公司 Magnetic ultrasonic contrast agent composition, magnetic ultrasonic contrast agent, magnetic microbubble ultrasonic contrast agent and preparation method thereof
WO2022001253A1 (en) * 2020-06-28 2022-01-06 南京超维景生物科技有限公司 Magnetic ultrasound contrast agent composition, magnetic ultrasound contrast agent, and magnetic microbubble ultrasound contrast agent and preparation method therefor
CN114210970A (en) * 2021-12-28 2022-03-22 北京建工环境修复股份有限公司 Coated iron-carbon composite material, preparation and modification methods thereof and sewage treatment method
CN114210970B (en) * 2021-12-28 2023-09-22 北京建工环境修复股份有限公司 Coated iron-carbon composite material, preparation method, modification method and sewage treatment method

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