CN1290488C - Micro bubble reagent in use for method of blood vessel embolism induced by ultrasonic and method of beauty culture of subtracting fat - Google Patents
Micro bubble reagent in use for method of blood vessel embolism induced by ultrasonic and method of beauty culture of subtracting fat Download PDFInfo
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- CN1290488C CN1290488C CNB031582915A CN03158291A CN1290488C CN 1290488 C CN1290488 C CN 1290488C CN B031582915 A CNB031582915 A CN B031582915A CN 03158291 A CN03158291 A CN 03158291A CN 1290488 C CN1290488 C CN 1290488C
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Abstract
The present invention relates to a medical microbubble reagent which is mainly used for ultrasonic inducement blood vessel embolization and beauty culture of fat reduction and is a carbon dioxide type microbubble reagent. The present invention comprises the steps: selecting a large molecular material as a carrier for packaging, sticking, stabilizing and carrying bubbles for the ultrasonic reagent; physically forming carbon dioxide gas microbubble reagents, and injecting carbon dioxide gases and liquid into solutions which are dissolved with the large molecular material under pressure; adopting carbon dioxide composed of organic acid and NaHCO3 to form the microbubble reagents. An injection mode of the ultrasonic microbubble reagents is used for forming capillary embolism agents or fat reduction cosmetology agents. Areas which need to be plugged are determined under the guidance of CT or type-B ultrasonic, such as tumor areas, ultrasonic energy is transferred to the areas of the ultrasonic microbubble reagents, and capillaries can form plugs; during fat reduction cosmetology, the microbubble reagents can be injected locally. Fat cell breakage is formed by inducement in a selective area.
Description
One, technical field
The present invention relates to be used for supersonic induced microvesicle reagent, comprise that preparation ultrasonic microbubble reagent is used to form the application of capillary embolism and fat reducing cosmesis because of cell cavitation formation blood vessel embolism art.Be used to form the capillary embolism art and eliminate a disease, also can be used for the fat reducing cosmesis.
Two, background technology
Ultrasonic microbubble reagent is a kind of reagent that is used for ultrasound detection, existing ultrasonic microbubble reagent has multiple, as by the reagent A lbunex of drugs approved by FDA clinical practice and Optison etc., fluorine carbon microvesicle reagent, normal saline system microvesicle reagent and following ultrasonic microbubble reagent: be listed as little show (German first Lin Ling company product)
1) Albunex human albumin peplos bubble liquid (Moleular Biosystems lnc.USA)
2) fso69 peplos bubble liquid, (Moleular Biosystems lnc.USA)
3) SHU454 galactose bubble liquid, (ScheringAG German)
4) SHU508 galactose bubble liquid, (ScheringAG German)
5)QW3600 (Sonus?Pharmaceuticals?Cosla?Mesa)
Can use fluorine carbon microvesicle reagent, its preparation is to get the human albumin solution, uses the supersonic vibration instrument.In albumin solution, at the uniform velocity inject fluorocarbon gas in the sonication process.Can use normal saline system microvesicle reagent, preparation process is roughly the same above-mentioned.
The ultrasonic microbubble reagent that the applicant proposes in Chinese patent application is used to form the application of capillary embolism, and the mode that ultrasonic microbubble reagent injects is as forming the capillary embolism agent, and the position that forms capillary embolism at needs is with the ultrasound wave effect.This regional blood capillary will form thromboembolism.The ultrasound wave of effect does not have particular requirement, generally adopts low-yield and low-frequency ultrasonic waves.Use low power ultrasound associating microvesicle reagent to act on band tumor animal, selective induction forms tiny blood vessels thromboembolism around the tumor, is a kind of method of new and effective tiny blood vessels thromboembolism, thereby provides new medicine and treatment approach for the blood vessel embolism treatment of tumor.
The mode that ultrasonic microbubble reagent is injected is as forming the capillary embolism agent, and irradiation is pressed close to ultrasound wave in the position that forms capillary embolism at needs, and selective induction forms regional tiny blood vessels thromboembolism.As long as adopt low-yield and low-frequency ultrasound wave, the processing time is also very wide, does not have particular determination, generally at 0.5-60 minute.And the medicinal scope that can use ultrasonic microbubble reagent to carry out is: fluorine carbon microvesicle reagent, normal saline system microvesicle reagent and the import ultrasonic microbubble reagent that can carry out commercial use.
Ultrasonic cavitation can make tissue produce cavitation in blink and cause cell generation acoustic horn effect, to macromole opening on every side or by the High Temperature High Pressure fragmentation.And organism the concentration of the cavitation nucleus in the body fluid is very low under normal conditions, produce cavitation effect and need use the high strength supersonic radiation, also cause the surrounding tissue damage when effectively killing target tissue, selectivity is low, damage is big, and can't be introduced into the blood vessel embolism treatment.Studies show that when containing microvesicle reagent in tissue, low dosage is ultrasonic can produce over the inductive acoustic horn effect of the simple ultrasonic ability of high power.The microvesicle reagent that the present invention uses in experiment is used for ultrasonic diagnosis at first, and it can arrive histoorgan with blood flow, improves the cavitation nucleus content of local organization.We only use lower powered ultrasonic radiation in experiment, can make microvesicle produce cavitation, broken blood capillary tube wall and part surrounding tissue activate endogenous or extrinsic coagulation, bring out large tracts of land blood capillary thrombosis and form the direct blood supply approach in blocking effect zone; And do not have the zone of microvesicle reagent, and rare thrombosis is found in the experiment, the blood vessel embolism rate that simple ultrasonic radiation effect causes is lower, only has 34.15% blood vessel that thromboembolism has in various degree taken place; Ultrasonic microbubble reagent is done the time spent, and the blood vessel embolism rate significantly improves, and reaches 89.11%.
Existing ultrasonic microbubble reagent comprises that the normal saline of mentioning, human albumin's ultrasonic reagent (being used for ultrasonic myocardial visualization etc.) are applied in clinical research.As to be listed as little show (German first Lin Ling company product) also be with the main component of macromolecular fatty acid as ultrasonic reagent.Therefore these macromolecular substances play parcel, stick, stablize and carry bubble in ultrasonic reagent effect is used in present ultrasonic reagent at large.Ultrasonic microbubble reagent mainly carries air, fluorocarbon gas etc., the ultrasonic microbubble reagent of import costs an arm and a leg, being used for the object of the invention may not be optimum, the effect that aeratings such as normal saline are stirred is good inadequately, fluorine carbon human albumin micro-bubble agent is that raw material makes from blood products, has the danger that causes irritated and blood source infectious disease.
Three, summary of the invention
The object of the invention provides a kind of application for preparing the microvesicle reagent of supersonic induced blood vessel embolism art and fat reducing cosmesis, comprises the application that ultrasonic microbubble reagent is used to form capillary embolism.The present invention also is a kind of by destruction of adipose tissue, thereby carries out the microvesicle reagent of cosmetic slimming art.In treatment or when operation, are reliable and stable, and use effective has no side effect to human body.The present invention especially provides the microvesicle reagent of the supersonic induced blood vessel embolism art of a kind of carbon dioxide-type.
The object of the present invention is achieved like this: a kind of application for preparing the microvesicle reagent of supersonic induced blood vessel embolism art and fat reducing cosmesis, it is characterized in that adopting carbon dioxide-type generation type microvesicle reagent, and comprise choose macromolecular material as the parcel of ultrasonic reagent, stick, stable and carry the carrier of bubble.In fact the present invention's application of ultrasonic microbubble reagent in induction of vascular Embolization or fat reducing beauty treatment just.
Macromolecular material has multiple choices, as comprise various plasma substitutes, autoblood, autologous plasma, homotype blood plasma, galactose, glucose, lactose, hetastarch (Hetastarch), human albumin (Human Serum Albumin), macrodex (Dextran-70), Dextran 40 (Dextran-40), Dextran 10 (Dextran-10), poly-gelatin (Polygeline), succinylated gelatin (Gelofusine), polyvidone (Polyvidone) or oxypolygelatin (Dxypolygelatin).And galactose, the glucose relative molecular weight is less, and viscosity is low, stablizes and carry the time weak point of bubble.
Concrete scheme of the present invention comprises two classes: first physics forms carbon dioxide microvesicle reagent, inject the solution that is dissolved with macromolecular substances at pressure carbon dioxide gas or liquid, it two is to comprise (Vitermin C) and NaHCO such as organic acid such as vitamin C
3The carbon dioxide chemistry that constitutes forms microvesicle reagent, vitamin C and NaHCO
3The two all can be used as medicine injection human body.The two reaction generates the carbon dioxide microbubble gas, can carry out the operation that the present invention implemented.The fat reducing cosmesis uses the microvesicle compositions and methods roughly the same, with the mode of ultrasonic microbubble reagent injection, and can locally inject the cavitation nucleator, presses close to irradiation at the position that needs fat reducing with ultrasound wave, and the adipose cell that selective induction forms accumulation destroys.As long as adopt low-yield and low-frequency ultrasound wave, the processing time is also very wide, does not have particular determination, generally at 0.5-60 minute.
For the particle diameter that guarantees the microbubble gas bubble and stable, choose macromolecular material as the parcel of ultrasonic reagent, stick, stable and carry the carrier of bubble, especially use plasma substitute class inclusion enclave, as hetastarch (Hetastarch) etc.
Generally speaking, the organic acid kind is a lot: as ascorbic acid (vitamin C), lactic acid, and Fructus Citri Limoniae (citron) acid, succinic acid, tartaric acid, acetic acid, lactobionic acid, galactobionic acid Galactonic acid, gluconic acid, glucosaminicacid, aminoacid etc.Especially inject citric acid, the lactic acid of pharmaceutical grade, gluconic acid, aminoacid are the selections of using always.
Carbon dioxide microbubble gas type
Typical prescription is as follows: vitamin C (Vitermin C comprises above-mentioned various organic acid) 25% (amounting to concentration 100%) NaHCO
350% (amounting to concentration 5%)
Hetastarch (Hetastarch) 25%
Per kilogram of body weight injection 1-10 milliliter, the microvesicle quantity of generation reaches every milliliter 10
8-10
10, particle diameter 1-10 micron,
Should calculate the carbon dioxide maximum amount of bearing by body weight height, body surface area during the clinical use of this reagent, in above-mentioned scope, adjust.
The characteristics of microvesicle reagent of the present invention:
1, belongs to the carbon dioxide-type micro-bubble agent, be easy to dissolving in vivo and discharge, reduce the probability that microbubble causes gas embolism with breathing from lung.
2, with (plasma substitutes) such as colloid hetastarch as colloid increase microbubble in blood stability, reduced the probability that carbon dioxide is discharged in lung.Keep the time of microvesicle long.
3, hetastarch substitutes human albumin's (as fluorine carbon human albumin micro-bubble agent), and no blood goods cause the danger of irritated and blood source infectious disease.
4, this kind micro-bubble agent is identical with other micro-bubble agent, can also can all can produce similar effect from peripheral intravenous injection from the feeding artery injection.
5, after the minimizing of microbubble quantity (part is discharged through pulmonary circulation), still be enough to as " cavitation nucleus ", under action of ultrasonic waves, produce " cavitation " and induce " acoustic horn effect ", damage small and little blood vessel wall, cause little endovascular thrombosis and the necrosis of tissue infraction property.
Remarkable result of the present invention, microvesicle reagent medicine itself is nontoxic to human body, medicine comprises the Therapeutic Method not damaged, no general toxicity side effect, determined curative effect is suitable for various malignant tumor by stages, the malignant tumor of body surfaces such as the abdominal cavity except that lung tumors, pelvic cavity, mammary gland, easy to operate, but repetitive therapy is easy to promote.In addition,, do not produce direct cytotoxicity, also can be used for carcinoid treatment because this therapy does not have the general toxicity side effect.
Four, description of drawings
Figure 1A tumor tissues is put to death after ultrasonic+micro-bubble agent effect immediately, sees blood vessel embolism and neoplasm necrosis
Figure 1B tumor tissues after ultrasonic+micro-bubble agent effect 1 hour is seen blood vessel embolism and neoplasm necrosis.Fig. 1 C tumor tissues after ultrasonic+micro-bubble agent effect 2 hours is seen blood vessel embolism and neoplasm necrosis.
Fig. 1 D tumor tissues after ultrasonic+micro-bubble agent effect 1 day is seen blood vessel embolism and neoplasm necrosis.
Five, the specific embodiment
Solid content proportion: vitamin C (Vitermin C) and NaHCO
3, plasma substitute such as starch proportion (weight ratio): 10-35: 1-3.5: 20-80, the ratio of solvent be solid content 3-10 doubly, NaHCO especially
3Concentration generally prepare at 3-10%.Aforementioned proportion also is applicable to citric acid, lactic acid, gluconic acid, and amino acid whose amount is more more.
NaHCO
3Be mixed with concentration 2-10% concentration and prepare, be more preferably NaHCO
3Be mixed with the solution of concentration 5%.Better scope is vitamin C (Vitermin C), citric acid, lactic acid, gluconic acid, aminoacid and NaHCO
3, plasma substitute such as starch proportion: 20-30: 2-3: 40-60.Because vitamin C organic acid and NaHCO such as (Vitermin C)
3, plasma substitute etc. all can be injected into human body separately, so do not need strict ratio, vitamin C (Vitermin C) and NaHCO
3Excessively all human body is not had very influence, plasma substitutes etc. are as the same.Certainly produce the carbon dioxide of fullest with the mol ratio preparation, the present invention is converted to the scope of percentage by weight.
Vitamin C organic acid and NaHCO such as (Vitermin C)
3The generation reaction generates carbon dioxide.Macromolecular material such as plasma substitute as the parcel of ultrasonic reagent, stick, stable and carry the carrier of bubble.The proportioning of three kinds of materials:
(1)20∶2∶40；(2)30∶3∶60；(3)25∶2.5∶50；(4)20∶2∶60；(5)30∶2∶60；
(6)30∶3∶40；(7)20∶3∶60；
(8)10∶2∶20；(9)10∶3.5∶80；(10)10∶3∶70；
(11)35∶2∶80；(12)35∶3.5∶70；(13)35∶3∶60；
(14)35∶2∶70；(15)10∶2.5∶50；
The also same citric acid of aforementioned proportion, lactic acid, aminoacid.
The present invention adopts the not significantly difference of plasma substitute articles for use of following state-promulgated pharmacopoeia registration:
1, hetastarch (Hetastarch), chemicals Sort Code: 401703060101
2, human albumin (Human Serum Albumin) chemicals Sort Code: 4021070102115
3, macrodex (Dextran-70) chemicals Sort Code: 401703030501
4, Dextran 40 (Dextran-40) chemicals Sort Code: 401703030401
5, Dextran 10 (Dextran-10) chemicals Sort Code: 401703030201
6, poly-gelatin (Polygelatin) chemicals Sort Code: 401703090201
7, succinylated gelatin (Gelofusine) chemicals Sort Code: 401703080101
8, polyvidone (Polyvidone) chemicals Sort Code: 401703050101
9, oxypolygelatin (Dxypolygelatin) chemicals Sort Code: 401703090101
Also comprise autoblood, autologous plasma, homotype blood plasma, galactose, glucose, lactose in addition.Above-mentioned galactose, glucose, independent even mixed interpolation does not all have marked difference.
The mode that ultrasonic microbubble reagent injects is as forming capillary embolism agent or fat reducing enamel, under the guiding of CT or B ultrasonic, need to determine the zone of thromboembolism, typical in tumor region, ultrasonic energy directly carries out the ultrasonic energy transmission by the body surface of contact to the zone that is filled with ultrasonic microbubble reagent, and blood capillary will form thromboembolism; Can carry out local injection microvesicle reagent during the fat reducing beauty treatment.Induce in the selective area and form adipose cell destruction.
The ultrasound wave of effect adopts low-yield and low-frequency ultrasound wave better; get final product as 20-50kHz; the output of ultrasonic transducer is about 1-100W; this energy injects; ultrasound wave itself can not cause any harmful effect to normal body, and various ultrasonic microbubble reagent all can become pharmaceutical usage of the present invention.
The mode that ultrasonic microbubble reagent injects is as (1) intra-arterial injection; (2) intravenous injection; (3) venous incubation or inlying catheter injection; (4) local injection.
Processing time is also very wide, generally at 0.5-60 minute.Not significantly difference of 2,5,20,30 minutes time periods when animal experiment.
Select amino acid whose embodiment for use: choose the medicinal of the more large production of usefulness or the cystine of infusing, lysine, glutamic acid, aspartic acid, phenylalanine, cysteine etc.The concrete ratio of embodiment is seen above-mentioned.
Embodiments of the invention following (effect photo in conjunction with the embodiments):
1, white mice is an experimental subject: simple ultrasonication, and can not be effectively to hair and blood pipe thromboembolism
2, heart (tremulous pulse) injection micro-bubble agent+ultrasound wave effect is respond well
3, all have no side effect through tail vein injection micro-bubble agent+ultrasound wave effect, good curative effect is arranged.
4, as NaHCO
3Be mixed with and amount to concentration 5%.
Better scope is vitamin C (Vitermin C) and NaHCO
3, plasma substitute ratio: 20-30: 2-3: 40-60.
Solvent often adopts water for injection.
The ratio of solvent is 4,6,8,10 times of not significantly differences of solid content, is mainly reflected in the content difference of microvesicle.
Physics forms the embodiment of carbon dioxide microvesicle reagent, under pressure medical carbon dioxide gas or liquid is injected the solution that is dissolved with macromolecular substances.Macromolecular substances comprises various plasma substitutes, autoblood, autologous plasma, homotype blood plasma, galactose, glucose, lactose etc.Band presses carbon dioxide microvesicle reagent must be kept in the pressurized tank, avoids before the unlatching rocking, and uses immediately after the unlatching, guarantees the content of microvesicle and the effect of use.
Claims (3)
1, a kind of application for preparing the microvesicle reagent of supersonic induced blood vessel embolism art and fat reducing cosmesis is characterized in that adopting organic acid and NaHCO
3Form carbon dioxide-type microvesicle reagent, and choose macromolecular material as the parcel of ultrasonic reagent, stick, stable and carry the carrier of bubble; Macromolecular material comprises plasma substitute, autoblood, autologous plasma, homotype blood plasma, galactose, glucose, lactose, hetastarch, human albumin, macrodex, Dextran 40, Dextran 10, poly-gelatin, succinylated gelatin, polyvidone or oxypolygelatin, described organic acid is vitamin C, lactic acid, citric acid, succinic acid, tartaric acid, acetic acid, lactobionic acid, galactobionic acid Galactonic acid, gluconic acid, glucosaminicacid or aminoacid, described organic acid and NaHCO
3, described macromolecular material three solid content part by weight be: 10-35: 2-3.5: 20-80, the ratio of solvent be solid content 3-10 doubly.
2,, it is characterized in that described organic acid adopts vitamin C, citric acid, lactic acid, gluconic acid or the aminoacid of injection pharmaceutical grade by the application of the microvesicle reagent of supersonic induced blood vessel embolism art of the described preparation of claim 1 and fat reducing cosmesis.
3, by the application of the microvesicle reagent of claim 1 or supersonic induced blood vessel embolism art of 2 described preparations and fat reducing cosmesis, it is characterized in that organic acid and NaHCO
3, macromolecular material three solid content part by weight be: 20-30: 2-2.5: 40-60.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031582915A CN1290488C (en) | 2003-09-23 | 2003-09-23 | Micro bubble reagent in use for method of blood vessel embolism induced by ultrasonic and method of beauty culture of subtracting fat |
| PCT/CN2004/000555 WO2005039526A1 (en) | 2003-08-18 | 2004-05-28 | Method, reagent and device for embolizing capillary vessel in tumor with supersonic tiny-bubble reagent |
| US10/556,237 US20070060906A1 (en) | 2003-08-18 | 2004-05-28 | Method, reagent, and device for embolizing blood vessels in tumors with ultrasonic radiation micro-bubble reagent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031582915A CN1290488C (en) | 2003-09-23 | 2003-09-23 | Micro bubble reagent in use for method of blood vessel embolism induced by ultrasonic and method of beauty culture of subtracting fat |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1600294A CN1600294A (en) | 2005-03-30 |
| CN1290488C true CN1290488C (en) | 2006-12-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB031582915A Expired - Fee Related CN1290488C (en) | 2003-08-18 | 2003-09-23 | Micro bubble reagent in use for method of blood vessel embolism induced by ultrasonic and method of beauty culture of subtracting fat |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1943541B (en) * | 2006-10-18 | 2010-05-12 | 许川山 | Supersonic micro bubble skin permeate promotor |
| CN107335098A (en) * | 2017-07-12 | 2017-11-10 | 江苏西宏生物医药有限公司 | A kind of injection implant of performance improvement |
| TWI686210B (en) | 2018-06-01 | 2020-03-01 | 國立清華大學 | Kit for normalizing blood vessels of lesions and use thereof |
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