CN1729020A - Medium for contrast enhancement or convenience for ultrasonic, endoscopic, and other medical examinations - Google Patents
Medium for contrast enhancement or convenience for ultrasonic, endoscopic, and other medical examinations Download PDFInfo
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- CN1729020A CN1729020A CN 03815474 CN03815474A CN1729020A CN 1729020 A CN1729020 A CN 1729020A CN 03815474 CN03815474 CN 03815474 CN 03815474 A CN03815474 A CN 03815474A CN 1729020 A CN1729020 A CN 1729020A
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Abstract
The present invention relates to a particularly convenient medium for providing contrast enhancement and/or distension of the subject body or organ cavity during imaging, radiographic, visualization, or other similar medical examinations, including ultrasound, endoscopic examinations, MRI, x-ray, hystero-salpingograms, CT scans, and similar procedures. The present invention provides the contrast enhancement and/or distends the body or organ cavity without constant leakage of the medium or the resulting need to constantly or repeatedly infuse additional medium. The medium is designed to have sufficient viscosity or consistence initially - whether as a solid, semi-solid, gel, viscous fluid, or otherwise - to remain in the body or organ cavity for a time generally sufficient to complete the procedure, and then to facilitate easy removal or expulsion from the cavity, preferably by liquefying or losing viscosity. For imaging and radiographic examinations, the medium may provide enhanced contrast as well as the distension of the cavity. For visualization examinations, the medium typically would be optically transparent but provide the convenient reliable distension. The phase or viscosity change may be triggered by a variety factors, such as the passage of time, a change in temperature or pH, the addition of another substance, or any other trigger that liquefies or otherwise facilitates easy removal or expulsion of the composition from the cavity.
Description
Invention field
The present invention relates to a kind of medium especially easily to take pictures, to provide in the process of radiography or other similar medical inspection and method the enhancing and the expansion of radiography in the imaging that relates to a kind of health or organ " void " chamber, radiation, comprise ultrasonic examination, endoscopy, nuclear magnetic resonance, X-ray, CT scan and similar method (being referred to as " medical imaging method ").The invention provides the enhancing of radiography and/or expand the normal of a kind of health or organ and be empty chamber, and do not have the seepage that continues of medium and do not need constantly, repeatedly or even change the contrast compositions of seepage continually.Though this medium is designed to have enough viscosityes at the beginning-as solid, semisolid, gel or mucus-keep one period that generally is enough to finish testing process at the intracavity of health or organ, liquefy subsequently or lose viscosity, be convenient to from the chamber, remove easily or discharge.Take pictures for imaging and radiation, this medium can provide enhanced radiography and expand described chamber.For contrast examination, this medium is generally on the optics transparent but provide for the necessary expansion of endoscopy video.
The present invention also relates to a kind ofly to use described medium easily to carry out imaging, radiation is taken pictures, is developed or the method for other similar medical inspection.
Background of invention
Ultrasonic and endoscopy is through being usually used in being positioned at or the medical observation of the various organs of contiguous various body cavitys.For example, can carry out ultra sonic imaging to the uterus easily.Originally design comes to promote to get the new saturating transvaginal probe of ovum in external fertilization (IVF), has further improved the quality and the purposes of uterine ultrasound video picture.This raising is directly because of altofrequency-high-resolution ultrasonic probe, probe, the vagina that inserts and analyzed organ-in this example between the uterus near making it to become possibility.
Clinical situation belongs to two main classes with the ultrasonoscopy in uterus.At pregnancy duration, usually use ultrasonic estimate fetal growth and health condition.And in nogestational women, ultrasonic through being usually used in identifying uterus pathology, as fibroma or polyp, particularly ought detect acquired symptom such as bleeding disorder (anovulatory dysfunctional uterine hemorrhage, or " DUB "), spasm and when infertile.
Remarkable difference between gestation and non-gravid uterus ultrasonoscopy is the existence of amniotic fluid in the uterus of gestation.At pregnancy duration, intrauterine (amniotic membrane) liquid acts on as a kind of significant contrast enhancer, has significantly improved the resolution of ultrasonoscopy.What strengthened by the radiography that provided by amniotic fluid to influence is those structures that are positioned at the immediate vicinity of fluid intermediate phase, as central nervous system structures.
Know the distinct advantages of pregnancy duration ultrasonoscopy and amniotic fluid as the contrast enhancer role, several inventors have attempted to reproduce these advantages for detecting nogestational uterus.Thereby for the quality of the ultrasonoscopy that improves non-gravid uterus similarly, researcheres are filled in the cavity of uterus ultrasonic transparent or ultrasonic opaque liquid so that the feminine gender (black) that obtains image or the enhancing of positive (white) radiography to be provided respectively.
The most normally, provide the ultrasonic clear solution of negative contrast-be slowly, and continually or repeatedly, infused in the cavity of uterus with 0.9% sodium chloride (NaCl, or normal saline) solution of about 10-40 milliliter-a kind of in ultrasonic examination, to keep suitable pressure to expand the uterus.This is usually being designed for the plastic catheter that the embryo shifts, or various other catheter models is carried out.Liquid must be constantly or repeatedly perfusion because-as liquid in the container of an opening with any supercharging can take place-it can pass through cervix uteri and/or fallopian tube seepage constantly in this case.Sometimes, conduit can be loaded onto the device of a kind of inflatable air bag or other sealing, and it can reduce the seepage in cervical end, but can not reduce oviducal seepage.
Today, this dabbling method of liquid that relates to during the uterine ultrasound program is called " hysterosonography " the most at large, although it also has other name, comprises the ultrasonic photography of hysterosalpingography (HyCoSY), saline hysterosonography etc.
Although simple in theory, NaCl or other solution are complicated and loaded down with trivial details as dabbling being applied in the practice of a kind of intrauterine of ultrasonic contrast reinforce.The intrauterine catheter importing intrauterine that after sight glass places, must at first will connect the NaCl syringe by cervical canal.Subsequently, need remove sight glass and simultaneously conduit be placed the uterus, so that hold ultrasonic probe inside vagina.At last, will pop one's head in a hands and to insert vagina, note not mobile conduit, another holds conduit and syringe simultaneously, the promotion piston is with promoter liquid stream in utero.Thereby, need one " pickpocket " so that ultrasonic machine is carried out the adjustment of any necessity, and preserve image file.
Because its seepage constantly need constantly pour contrast solution by cavity of uterus when carrying out ultrasonic examination, this has also caused inconvenience and in the soiling solution turbidity current of test zone, be included in to check on the operating-table-this can become the other uncomfortable source of patient.Needless to say, the uterine ultrasound radiography is thought a kind of method consuming time by most of gynecologists, and they reluctantly make in this way and only are considered to have just use in extra inconvenience and the uncomfortable situation at some.Although these practical difficulties are arranged, the improvement of the ultrasonoscopy that obtains by hysterosonography but is significant and the diagnosis that brings accurate more uterus pathology such as leiomyoma of uterus and polyp, otherwise ultrasonicly goes to check to be impossible or difficult with usual.
Improved contrast ultrasound provides the better image of intrauterine pathology.Referring to, for example, Fig. 1 to 4.Figure 1A, 2A, 3A and 4A show a kind of usual uterine ultrasound everyone result in four patients.Figure 1B, 2B, 3B and 4B are presented at a kind of result through improved contrast ultrasound who uses medium of the present invention of same four patients respectively.Contrast that the essence that obtains with the present invention improves and visibility in addition with obtained with general hysterosonography (it does not bring convenience of the present invention and the benefit of discussing below) similar.
A lot of researchs have been confirmed by add the improvement that the intrauterine contrast agent brings on general uterine ultrasound radiography.Specifically, mass data has proved that when comparing with general uterine ultrasound the normal saline hysterosonography is for the superior positive or negative predictive value of differentiating intrauterine pathology.The pathology of identifying easily by hysterosonography comprises submucous fibroid and endometrial polyp, the common reason of two kinds of anovulatory dysfunctional uterine hemorrhages.Yet although the abundant clinical value of being put down in writing by many academic researchs is arranged, because the difficulty and the property consuming time of this method, the practical application of hysterosonography is still relatively limited.Make hysterosonography on daily gynecology, can not get widespread usage just because of these actual reasons.
Ultrasonic-opaque solution such as EchovistR-200, AlbunexR or similar product and need not ultrasonic-transparent solution such as normal normal saline are used in mutation of normal saline hysterosonography, so that make cavity of uterus become hyperechoic (" white ") but not hypoechoic (" black ")." white " hyperechoic contrast agent had obtained fierce the discussion with respect to for example brinish value of " black " low echo product.
For the hysterosonography of utilizing high echo (" white ") medium, the product of use (Echovist and similar products like) designed to be used the enhancing of intravascular injection and contrast echocardiography.Therefore, their application on obstetrics and gynecology are the ideas that afterwards just has.They all are liquid and need hang down echo product as NaCl or other " black " in the perfusion in the whole process.When the relative shortage contrast when being used for imaging with the hysterosonography of using negative contrast medium (as normal saline) is compared, the advantage of the method for a kind of high echo type that has carried out claim or opaque contrast medium is the oviducal image that improves contrast, particularly its proximal part that obtains.
Yet, today is when recognizing that as many doctors the positive contrast hysterosonography can be used in the opening of check fallopian tube, classical uterus and fallopian tube photography (HSG), a kind of inspection of using X-ray, because the superior quality of gained fallopian tube image remains the anatomical basic mode of research fallopian tube.Though when our approval was better than the positive contrast hysterosonography usually for assessment fallopian tube anatomy HSG, we believed that the positive contrast hysterosonography can work for the oviducal function of research (contraction of wriggling)
Do not consider its indication, the method for positive contrast hysterosonography the same with negative hysterosonography loaded down with trivial details " 3 handss ".It also needs to inject simultaneously the contrasting fluid, holds ultrasonic probe and carry out necessary adjustment on ultrasonic device.Because positive contrast goods such as Echovist-200 are injectable flowing products, these products generally still need during checking to carry out constantly or periodically inject.Therefore, these methods also need during operation conduit to be remained in the cavity of uterus so that continue or frequent medium replenishes, and cause usually in the offending damp seepage of checking on the operating-table.
Opposite with ultrasonic method, uteroscopy is a kind of endoscopy of uterus so that a kind of direct development is provided, but not a kind of contrast images.Correspondingly, such method does not generally need to use contrast medium, but it still uses a kind of " figure image intensifying " medium is with the expansion uterus, otherwise it will be an empty chamber-be " it is flat to collapse " and thereby be difficult to develop.Although this method is helpful, has the significant disadvantage that hinders its extensive use.These shortcomings are included in pain and the discomfort that operating period brings to patient, and need sterilize again to the equipment of costliness after each the inspection.
During uteroscopy, metroscope is imported cavity of uterus by cervical orifice.In the uteroscopy of operation property, this operates under the anesthesia and carries out, and it typically is general anesthesia, but can be spinal column or part (cervical vertebra) anesthesia.
This method generally need be inserted big relatively apparatus-operating hysteroscope to 7-9mm with permission with cervical dilatation.Need a kind of solution, as a kind of NaCl solution, Ringer's solution or glycine (if considering monopolar coagulation), or a kind of gas, as CO
2Lasting perfusion, hemorrhage with continuous expansion cavity and flush away.
In some cases, a kind of dense thick solution of perfusion in the uteroscopy process is as Hyscon
TMAlthough thickness is also dense a little than normal saline, Hyscon self still can not expand cavity when pouring under pressure.And also seepage of Hyscon, thereby this method needs perfusion that continue or periodic again.
Metroscope is configuration by this way generally, promptly if desired, can insert miniature surgical instruments with excision or remove abnormal structure such as polyp, sub-endometrial fibroids and scar tissue (adhesion) by metroscope, or use electric coagulation or laser beam to burn and remove them.The metroscope of correspondingly, operation property will not be tending towards compact.
Office hysteroscopy is a kind of version of simplification, only makes the purpose of diagnosis.The less instrument size (diameter 3-5mm) that is used for office hysteroscopy makes the doctor can avoid cervical dilatation and anesthesia.Even so, pain and discomfort still are accompanied by this operation, so how many reports of this formal operations also is restricted.Owing in the uteroscopy of operation property, must in the whole operation process, pour into a kind of solution or gas,, thereby can develop with the expansion cavity of uterus.Certainly, the confusion that perfusion itself (it takes place under pressure) and general seepage are followed is patient's additional sources of discomfort.
Thereby, a kind of bringing (1) ultrasonic contrast enhancing characteristic negative or male intrauterine contrast medium and slight expansion cavity of uterus be ne-leakage so that the radiography intermediate phase to be provided, the liquid perfusion that described seepage need continue during ultrasonic examination, or the needed expansion of (2) hysteroscopy procedures, bring optical clarity simultaneously, but do not need huge apparatus pouring into medium constantly, or bring the product of the two, will all bring great advance aspect these two of this field.Such product will make this method still less loaded down with trivial details, do not accommodate confusion, and convenient and effective.
Such product should have tremelloid viscosity, perhaps can in utero be retained in the uterine cavity after the perfusion during checking.This will make the doctor remove sight glass and intrauterine catheters after perfusion, and carry out ultrasonic or uteroscopy operation and needn't during checking continue to pour into this product.An extra benefit is that the image that produces does not have the image artefact that is produced by intrauterine catheters.Ideal product should perhaps be convenient to remove easily, thereby it can forever not keep after ultrasonic examination is finished, and not discharge from cavity of uterus reasonably liquefying after period.A kind of material that keeps the viscous adhesive denseness is unsuitable in utero being detained, because may influence fertility.
As used herein, a kind of " figure image intensifying " medium meaning is a kind of medium that strengthens or improve radiography and/or chemical development in the medical inspection operating process, as in a kind of operation as ultrasonic or endoscopic procedures by expansion body cavity or tissue lumen, and/or by formation method such as ultrasonic during bring enhanced contrast.Thereby, use radiography to strengthen here than only strengthening or to improve the simple meaning of contrastographic picture more broad.On the contrary, suitably use this term here in context, refer generally to generation strengthen or promote imaging, radiation to take pictures, manifest and similar techniques, no matter be literal raising contrast, or by promoting to be examined the expansion on surface, or the two.
As used herein, " phase change " or " changing mutually " medium is a kind of medium, it begins in the medical inspection process is comparatively solid or semisolidization (brood lac as), but change or change into comparatively fluidization subsequently to promote by removing or discharging in the described chamber, preferably after checking process is finished.By contrast, " viscosity change " or " viscosity transformation " medium is a kind of medium, more tacky when it is used for a kind of body cavity or tissue lumen in the medical inspection process, but become comparatively not sticking subsequently to promote by removing or discharging in the described chamber, preferably after checking process is finished.
As used herein, a kind of medium with a kind of " solid ", " semisolid " or " glue " state or existence mutually is to be in physically basicly stable form (promptly, relatively solidify or sticking and on-liquid or gas), in the medical inspection process, being retained in basically in body cavity or the tissue lumen, and generally do not need that continue or frequent replenishing.
As used herein, " time enough " that carry out the medical inspection process is generally a few minutes, and common 3 to 10 minutes, preferred 5 to 7 minutes.After being placed such time enough to compositions of the present invention, checking process has been finished usually.No matter it is liquefaction or reduction viscosity, said composition subsequently can be by oozing out in body cavity or the tissue lumen, or removed easily rapidly.Common this chamber essentially no said composition in its 7 to 20 minutes of starting from placing in the chamber is preferably in about 10 to 15 minutes.
As used herein, " medical imaging " is that imaging, the radiation of digital examination body cavity or tissue lumen or adjacent tissue taken pictures, developed or other similar method, be used for various purposes, no matter comprise assessment, diagnosis, observation, treatment etc., be to warn or just as preventive measure by concrete related symptoms.This method comprises, for example ultrasonic, endoscopic procedures, X ray, hysterosalpingography and CT (X ray computer aided transverse tomography) scanning (each all is a kind of " medical imaging method ").Similarly, consider a kind of medical imaging compositions or medium are used for this medical imaging method.
Summary of the invention
The present invention relates to a kind of medical imaging compositions that is used to relate to the medical imaging method of a kind of body cavity or tissue lumen.Said composition generally comprises a kind of enhancing image with initial viscosity or denseness, changes the medium of viscosity, and it is importing in health or the organ or afterwards, is being enough to keep a period of time substantially at intracavity, and this time is enough to allow imaging process be accomplished.Valuably, said composition also has a kind of viscosity that weakens subsequently or denseness, thereby it is fully weakened this medium is able to easily by discharging in body cavity or the tissue lumen or removing.
In one embodiment of the invention, this medium is importing in health or the organ or is beginning afterwards to be solid, semisolid or colloid, thereby this medium need not carry out constantly in imaging process or administration continually.In this embodiment, this medium is liquefaction over time or reduction viscosity generally, thereby it can be easily by discharging in body cavity or the tissue lumen or removing.
In a specific embodiment of the present invention, this medium is designed to have the characteristic that the said composition of making is applicable to that transvaginal sonography is checked.
In other embodiments, this medium be designed to respond said composition on temperature specific change and liquefy or reduce viscosity.
This medium can comprise one or more polymer and preferred one or more adjuvants or therapeutic agent.Used adjuvant or therapeutic agent generally comprise a kind of anti-infective or a kind of radiation opacifying agent.
The invention still further relates to a kind of method at body cavity or the enterprising imaging operation of practising medicine of tissue lumen.In one embodiment, this method comprises that (a) places a chamber with compositions of the present invention, in the uterus, (b) carry out imaging operation, and (c) removes or make said composition to discharge from the chamber subsequently.
The invention further relates to medium of the present invention and making a kind of image enhancing composition to be used in the application in the formation method that relates to a kind of body cavity or tissue lumen.Used medium generally has enough viscosity, thereby it need not carry out administration constantly or continually in operating process, and it is discharged from the chamber easily after the sufficient time that operation is normally finished or removes.
In any of these embodiment, initial viscosity or solid, solid-like or gel state can partly or wholly be provided by other component of using a kind of polymer or this medium.
Medium of the present invention is with less pressure expanded body cavity or tissue lumen, and carries out the medical imaging in chamber under the dabbling situation of the extra media that does not continue simultaneously.Fine image all was possible before medium liquefaction generally, at this moment checked and may worsen because of the loss of vision degradation or medium.Specially make medium provide plenty of time to detect cavity of uterus up hill and dale without any need for the perfusion that continues, but if desired inspection is kept the longer time, can use usually for the second time or more frequently and use.
The accompanying drawing summary
Figure 1A and 1B show for a kind of usual ultrasonic and a kind of use of patient #1 of the present invention ultrasonic respectively.Figure 1B shows that the positive of endometrial polyp is found (10) and it does not show in Figure 1A.The histology has confirmed the existence of a polyp.
Fig. 2 A and 2B show for a kind of usual ultrasonic and a kind of use of patient #2 of the present invention ultrasonic respectively.Fig. 2 B shows the indication endometrial polyp or fibromatously positively finds (11) and it does not show in Fig. 2 A.The histology has confirmed the existence of a polyp.
Fig. 3 A and 3B show for a kind of usual ultrasonic and a kind of use of patient #3 of the present invention ultrasonic respectively.Fig. 3 B shows that the positive of indication endometrial polyp is found (10) and it does not show in Fig. 3 A.The histology has confirmed the existence of a polyp.
Fig. 4 A and 4B show for a kind of usual ultrasonic and a kind of use of patient # 4 of the present invention ultrasonic respectively.Fig. 4 B shows the indication endometrial polyp or fibromatously positively finds (11) and it does not show in Fig. 4 A.The histology has confirmed the existence of a polyp.
Fig. 5 A and 6 shows for two other patient's use uteroscopy result of the present invention.Fig. 5 shows a metropolypus (12), and Fig. 6 has shown a metrosynizesis or cicatrix (13).Two discoveries obtain confirming by operation temper palace spectroscopy subsequently.
Detailed Description Of The Invention
For such as the inspection of body cavity or tissue lumen, assessment, diagnosis, treatment, observe and check Purpose the invention provides easily radiography enhancing composition and is used as the medical imaging method (as becoming The picture, the radiation take pictures, develop or other similar medical procedures) medium. These chambeies are generally " void " chamber, namely their flat or gauffers that is tending towards collapsing are similar with an air balls, rather than expansion With open but hollow.
Such method comprises, for example, ultrasonic, endoscopy, magnetic resonance imaging, X-ray, Utero-Salpingography and CT scan. This medium will bring, and will be secure for ad hoc approach Be fit to, the radiography of physiological saline or similar perfusion strengthens characteristic. This radiography strengthens effect can With by in the middle of a kind of " black " mutually as by physiological saline or a kind of similar solution were provided or Provided " white " middle phase by a kind of high echo type solution, caused such as Echovist. Under the both of these case, around the centre that is provided by contrast preparation is different from mutually with different colourities or The structure that gray-level structure occurs. No matter whether radiography strengthens is desired, this medium also can tool Have keep motionless ability and do not have obvious seepage or in operating process, continue or periodically mend The necessity of filling changes after the time enough of complete operation mutually or viscosity simultaneously, or otherwise Has the ability of from body cavity or tissue lumen, discharging easily or removing at that time.
The reduction of the needed pressure of this medium of instiling has reduced the degree of patient's discomfort. This Bright medium generally can instil under lower pressure, because it needn't overcome by son The seepage of uterine neck and conduit, and than the time much less of former medium under pressure, simultaneously Still expand fully body cavity or organ. On this pressure and pressure duration on fall Hanging down to help to make patient's discomfort to minimize. And, there has not been during operation the conduit of passing through The uncomfortable degree of use the inventive method will further be alleviated to oozing out in a large number of pelvis.
The present invention will be effectively in various medical imaging methods, no matter be for observing, examining Disconnected, treatment or other purpose, comprise without limitation traditional " imaging " method such as X-ray, Ultrasonic, CT scan or magnetic resonance imaging; Radiography research is such as HS G or CT scan; Or directly Developing technique such as endoscopy.
As discussed above, in ultrasonic on being applied to the gravid woman, amniotic fluid is as a kind of Intrauterine contrast enhancer and working provides sound wave interface a kind of feminine gender or " black ". In nogestational uterus, uterine cavity is owing to lack the gauffer and stingy that withers in radiography interface-uterus Capsule and be difficult for to develop can not present detailed image. Therefore, the image of normal and pathology (as Polyp, subcutaneous mucous membrane fibroma) often not enough clear to make a definite diagnosis.
Hysterosonography mimics is to the ultrasonic condition of pregnant woman, and the figure of excellent quality is provided Picture. Yet loaded down with trivial details, the consuming time and difficult usefulness of hysterosonography generally needs more than one The people carry out. The present invention attempts to provide the key benefits of hysterosonography to avoid simultaneously this A little subject matters.
Use the hysterosonography of high echo (" white ") medium to be advocated to study son Palace pathology and fallopian tubal anatomy (opening). Used product (Echovist and similar producing Product) be designed to intravascular injection and strengthen the contrast of cardiac ultrasonic. It is on gynecotokology Application be the idea that just had afterwards. These products are also need to advancing in whole process of liquid The row perfusion is just as NaCl solution.
These products of empirical discovery are for identifying pathology in the uterus, such as polyp and subcutaneous mucous membrane fiber Knurl is superior unlike NaCl solution. Some doctors think that these products produce the tendency of hatching effect So that they more behave desired not as physiological saline. Yet for tubal assessment, find white The look radiography is better than feminine gender (" black ") medium to a certain extent, such as physiological saline. Even if So, these products still have been subjected to query for detecting the anatomical value of fallopian tubal, because HSG (X-ray) is so superior. We think that " white " product can prove to have Effect in the research Tubal Function of Sterility.
A specific embodiment of the present invention is used a kind of hysterography medium that changes mutually (PSCM) obtain the quality of uterus image, described image obtains with hysterosonography, Simplicity that conventional transvaginal sonography uses and great property have easily been kept simultaneously. Referring to, for example, The following examples 1. When with embryo's transfer conduit instillation uterus of a routine, this medium is Stiff and suitably expand uterine cavity. The special PSCM of the used acoustic characteristic with water, Provide the radiography a kind of feminine gender or " black " can be to protruding the structure in the chamber, such as breath Meat and/or sub-mucosal fibroids are carried out splendid development. Given by the characteristic that changes phase, PSCM liquefies when its temperature rise and when reaching body temperature subsequently. In case become liquid, metreurysma Finish and PSCM is discharged.
Thereby a specific embodiment of the present invention will be a kind of gel that is used to carry out the water sample of uterine ultrasound operation, and the radiography with " white " or " black " strengthens characteristic.This glue can remain in the cavity of uterus in the time of examinations of uterus.After the time of a setting, usually approximately after 3-10 minute, this dispergation and discharge by the uterus wriggling.This discharge is similar between the normal saline flush phase of prior art, as the discharge of the reservation amount of not oozing out the uterus during hysterosonography.
The viscosity of prescribing a time limit in one embodiment, is temperature dependent.Such chemical compound for example, in room temperature or the colder initial viscosity that can have height down when inserting intrauterine, reaches body temperature up to it, in its loses viscosity of this point, and the liquefaction more that becomes, and discharge rapidly.This just allows with a kind of simple catheter uterine gel of film chamber instillation 2-7cc in uterus, described catheter is similar to those that are used as embryo's transfer in uterus in (IUI) process of being fertilized, and uses the cleaning method and the preventive measure that are widely used in IUIs and the operation of all intrauterine.
For ultrasonic method, remove conduit and sight glass subsequently, carry out ultrasonic examination as generally for vagina and abdominal ultrasonic.Uterine gel keeps its viscosity time enough to finish ultrasonic examination, simultaneously from before benefit the same radiography enhancing that only could obtain with the hysterosonography operation of " 3 handss " of complexity.
For hysteroscopy procedures, generally can use the medium of same general type, but it does not need to provide the enhancing of radiography usually.On the contrary, such medium can be transparent on the optics usually.
The inside looks of uteroscopy chemical development cavity of uterus.In operating process, need the uterus is manually expanded with the acquisition panorama, rather than only check Uterus wall that wither, gauffer.Used apparatus (metroscope) combines the fiber optics system that illumination is provided and allows to observe in cavity of uterus, and in the mechanism that is enough to expand primer solution under the pressure of uterine cavity or gas, thereby can carry out the video picture of Uterus wall.Be only limited to the office hysteroscopy of diagnosis, use miniature instrument so that discomfort minimizes, described discomfort is to be associated with their insertions by cervical canal.Yet the complexity that is miniaturized as current metroscope is limit, and particularly needs device for casting and optical system are combined.Limitation on these engineerings makes clinic metroscope suitable pain still, thereby has hindered its routine and frequent application.
In that metroscope microminiaturization and making is operated in the effort of pain still less, developed the uterus microscopy of compact.The uterus microscopy of compact comprises mucosa and endometrium mucosa in the chemical development cervix uteri and needn't expand cavity of uterus, and thereby need not obtain the panorama video picture of uterine cavity.For this reason, use characteristic is the rigidity mirror of a single glass column, and does not comprise a kind of sheath of device for casting, with mucosa in the chemical development cervix uteri and endometrium mucosa.When observing by a kind of optical system of amplification, it can carry out the histodiagnosis of mucous layer (endocervix and endometrium) to a certain extent.Therefore, the contact hysteroscopy art is used to screen cancer, hemorrhage histology's reason also may be screened the endometrial function time.But owing to cavity of uterus is not expanded, contact hysteroscopy does not provide for diagnosis endometrial polyp or the necessary panorama of submucous fibroid, and they are the most common anatomy reasons that need the anovulatory dysfunctional uterine hemorrhage (DUB) that operation removes.
Break away from the needs that pour into inflation fluid or gas for the endoscopic exploration that makes cavity of uterus, can use a kind of medium (PSM) that is preferably transparent transformation phase.Such novel medium is passable, for example, at room temperature has very heavy-gravity characteristic, so that the expansion of cavity of uterus to be provided during endoscopy.It liquefies after a few minutes in the arrival room temperature subsequently, and discharges from cavity of uterus naturally.
Provisional glue phase like this, or the viscous characteristics of other effective medium, can as above discuss is heat-sensing, perhaps it can become a kind of compositions of fluidization more over time.Preferably, this medium has mutually and to change or characteristic that viscosity changes, makes it can become a kind of form of more fluidization from a kind of semisolid or solid (brood lac as).The persistent period of the character of this variation and variation and triggering can depend on one or more factors in the physical characteristic of this medium.For example, triggering the factor that in form changes can be owing to various condition, as the variation on pH, temperature, shearing force or pressure; The existing of other preparation (for example salt, solvent, acidity or alkaline material); Applying of an electromotive force; Or only be the passing of time.In case the characteristic of the medium that has changed-it become fluidization more-make it can equally discharge at any other the liquid of the phase transition process after image of finishing it.
Depend on the specific composition of medium, this medium both can provide a kind of feminine gender (black) that a kind of positive (white) contrast adjunct also can be provided in ultra sonic imaging.Phase-the transformation of this medium or the characteristic of viscosity-transformation are preferably used as the empty chamber for health or organ, as ultra sonic imaging or Endoscopic a kind of image reinforce in uterus.
Thermo-responsive or other temporary viscosity of the present invention can trace back to the glue-formation characteristic of some active ingredient in pharmaceutical composition.For example, some polymer as carbomer 934 P or carbomer 974P, can provide " temporary " viscosity by this way.These polymer or other component are known useful in the dosage form that can be temporary transient viscosity is provided, for example, be used under a kind of lower temperature for viscosity but in the compositions that liquefies during subsequently at body temperature or near body temperature, or can be used for before a kind of the liquefaction in the dosage form for short-term viscosity.In addition,, also other preparation or adjuvant can be joined in the compositions if needs are arranged, as, for example infection medicament, radiation-opaque medicament, weaken graininess or improve the compositions aesthetic feeling medicament, or antiseptic.
Certainly, as arbitrary those skilled in the art can recognize easily, the present invention can have widely and to use.For example, the ultrasonic or endoscopy of other body cavity or organ (except vagina or cavity of uterus) is also promoted by utilization of the present invention.Similarly, other medical imaging method as X-ray or nuclear magnetic resonance, also can benefit from this invention.
In addition, although temporary viscosity or curing are importances of most of embodiments of the present invention, the accurate mechanism or the method itself of liquefaction or other conversion composition are unimportant.The transformation of liquefaction or other phase or denseness can originate from, for example as above certain variation on temperature of considering, or only behind certain hour, or after adding other medicament, as long as medium after the administration be at first viscosity and liquefaction or promote to remove after being enough to the time of complete operation in short relatively and a predictable period subsequently at one section.Certainly, the present invention also can implement with a kind of compositions, and said composition is enough sticking so that maintenance as desired is motionless, yet it still can be discharged or remove under the situation that does not have viscosity or consistency change.
The specific benefits that the invention provides or support uteroscopy to use comprises following:
1. do not follow the uteroscopy that continues a kind of solution of perfusion or gas;
2. than the development of the metroscope device of minor diameter, do not have device for casting (pipeline, sheath etc.), can utilize plastics or other material, this can promote the development of disposable apparatus.The clinic metroscope of the simplification that these are novel (disposable or non-once) can be connected to be observed on the camera, allows to carry out the immediate observation and the record of image or image sequence.
Medium can be solid or semi-solid state before importing body cavity, or can change solid or semi-solid phase into when importing body cavity.Medium also can be semisolid or solid before or after settling, and changed phase but import the back at other material (for example salt, acidity or alkaline matter, or solvent), and the importing of described other material will cause the generation that changes mutually and medium is liquefied.
Provide the desired phase or the composition that can be used in the media compositions of viscosity characteristics to include but not limited to polymer (as carbomer, methylcellulose, gelatin, agar, baregin, starch, high molecular weight polyethylene glycol), copolymer (as poloxamer) and Colloidal Clay class (as bentonite or Tragacanth).Thixotropic admixture also is considered to potentially useful as medium.The mixture of such inorganic matter can be as expander to promote development.
Ideally, a kind of product that strengthens image is nontoxic as far as possible to uterine mucosa and gamete.Can develop various products and strengthen characteristic, to be used in formation method such as the ultrasonic method with the radiography that " feminine gender " and " positive " is provided respectively.
Generally for identifying that the uterus pathology protrusion in cavity of uterus is best as sub-endometrial fibroids, endometrial polyp and metrosynizesis and deformity, these pathology protrude often may cause anovulatory dysfunctional uterine hemorrhage or infertile to negative contrast medium.The positive contrast reinforcing agent is generally for imaging, and for example fallopian tube is useful.Using in order or being used in combination of feminine gender and positive contrast reinforcing agent can be as two contrast imagings, as what can guarantee under specific environment.
The primary application that exceeds the positive ultrasonic contrast reinforcing agent of purpose is expanded in the possible clinical practice of positive contrast products, as Echovist.When Echovist is used to develop pipeline anatomy, we think that our positive ultrasonic contrast reinforce also can act on research uterus and fallopian tube physiology, for example studied menstrual cycle mid-term the mainly sperm transmission by retrograde contractility (that is, leaving vagina-) to substrate/conduit by cervix uteri.Other application of positive contrast reinforcing agent will be, for example, research in menstrual phase when the tolerant discharge of being undertaken by the uterus wriggling of intrauterine should normally be direct motion (to cervix uteri) substantially the contractility in uterus.The another kind of variant of uterine ultrasound contrast medium be designed to study the transmission of vagina-fallopian tube with attempt to evaluate sperm menstrual cycle mid-term to uterus and oviducal normal displacement.Certainly, other application can become apparent to those skilled in the art.
Similarly, do not need to continue a kind of solution of perfusion or gas and the ability of carrying out office hysteroscopy has been opened the new probability in this field, as development much smaller than the device of existing product.Because the main cause of the quantity that pain that experiences in operation and discomfort are restrictions to be checked, it is conclusive using the potentiality of the device that significantly dwindles.Current, device size the only about half of of (diameter) is used to hold filling system, and essential coaxial sheath separates optical fiber and perfusion cannula.
If hysteroscopy procedures does not need the filling system (solution or gas) that continues, just can be easily how develop the technology option of new and innovative with the development cavity of uterus.Can only use plastic optical fiber and development system has the cheap disposable intrauterine apparatus or the potentiality of adnexa to this apparatus, rather than need be between patient the non-once apparatus of disinfectant costliness again.These less new instruments can import cavity of uterus near the size of the current plastic catheter that is used in utero being fertilized relatively painlessly after cavity of uterus is full of medium.Benefit like this is outer will to make this method be used more routinely, for example study common intrauterine pathology, as polyp or sub-endometrial fibroids, or the diagnostic exploration of the possible endometrial anomalies (polyp etc.) of assessment infertile women.
Therefore, a kind of allow uteroscopy do not need to expand solution or gas continue or frequent perfusion and a kind of invention of being carried out have by helping to make the real painless potentiality that help to reform uteroscopy of uteroscopy, and thereby be useful more routinely.In addition, it may bring new, that obviously simplify more and littler, and may be the development of disposable apparatus, and extra convenience and benefit is provided.
Fig. 1 to 6 has shown the result who uses the present invention to be obtained in ultrasonic and endoscopic procedures.Figure 1A, 2A, 3A and 4A are the usual ultransonic images (no contrast media) that carries out at four different patients.Figure 1B, 2B, 3B and 4B are the images available from the very same patient of utilizing hysterosonography of the present invention.In each case, utilize the present invention to show a kind of polyp or fibroma that is not arrived, and do not have the difficult and inconvenient of traditional hysterosonography by general ultrasound observation.
And Fig. 5 and 6 is the images that obtain in two patients in utilizing hysterosonography process of the present invention.These operations have disclosed tangible physiological abnormalities with definitions of traditional uteroscopy, and the general difficulty that has of ametria spectroscopy, do not accommodate inconvenience.
Embodiment
A kind of sample formulation can followingly be prepared.3 gram carbomer 934P are sieved under room temperature in the purified water of 900ml and simultaneously water are stirred.In case all carbomers are sneaked in the water, can add 10 Keshan pears sugar alcohols to reduce granulation.An amount of purified water (produce 1000ml cumulative volume) and sodium chloride moles such as (make the product that obtains etc.) blending are joined in the mixture.Subsequently with low shear force with the mucus rapid mixing that forms 15-30 minute.Allowing mixture place need not stir so that any lather collapse in 30 minutes.Regulate pH to 7.4 with sodium hydroxide.The gas of mixture is discharged.
The following examples 1 and 2 have reflected that wherein we utilize a kind of research of commercial existing similar compositions.Lacryvisc
TMBe a kind of ophthalmic gel of making by Alcon, comprise 0.3% carbomer 934 P, Sorbitol, sodium hydroxide (pH buffer), Benasept (antiseptic) and purified water.Lacryvisc being filled into intrauterine, it is cooled to about 35-40 degrees Fahrenheit with before carrying out these operations.But usually, we preferably use a kind of dosage form, and its (1) does not need to cool off before use, and (2) it in the end carry out disinfection and thereby do not need antiseptic.
Embodiment 1: contrast ultrasound-53 patient
Design-prediction feasibility study in infertile women and anovulatory dysfunctional uterine hemorrhage (DUB) women.
Material and method-women of 53 inquirings infertile (n=27) or anovulatory dysfunctional uterine hemorrhage (n=26) is studied.After carrying out traditional transvaginal sonography, the somebody of institute is carried out the contrast ultrasound inspection.For this reason, using a kind of 3.5Frydman embryo transfer catheter that the feminine gender (black) of 3-7cc is changed contrast agent (" PSCM ") mutually is poured in the cavity of uterus.Subsequently this uterine catheter is removed and carry out another time transvaginal sonography.
The result-in all women, cavity of uterus keeps expansion greater than 3 minutes, and stiff " black " interface greater than 3.5mm is stayed in cavity of uterus.Metreurysma after 10 minutes in all patients and contrast agent disappear.Suffer among 21 of anovulatory dysfunctional uterine hemorrhage at 26, contrast ultrasound has shown a kind of intrauterine pathology, and it is confirmed by uteroscopy and histology subsequently.14 people in them, traditional transvaginal sonography does not provide definite diagnosis.
Discussion-use gel of the present invention is painless.Patient does not complain discomfort and does not need the pain medication.
Conclusion-this has reported the development of a kind of novel PSCM, and its produces the moderate expansion of cavity of uterus in limited time, provide a kind of ultrasonic-transparent (" black ") intermediate phase.This provides " contrast ultrasound " image, and it has greatly promoted intrauterine structure such as polyp and fibromatous positive diagnosis.Use that the hysterography of PSCM is ultrasonic may to make uterus sonography generation revolutionary change,, kept the simplicity of the property easily used and common saturating transvaginal sonography simultaneously because it provides the image with hysterosonography quality.
Embodiment 2: endoscopy image-7 patient of cavity of uterus
The first feasibility study of design-in the women of the predetermined temper palace spectroscopy that undergos surgery uses optics-transparent medium of transformation mutually (" PSM ").
Material and method-before will beginning at once, predetermined operation temper palace spectroscopy in 7 women, PSM is tested.Use a kind of common embryo to move to grow conduit and after patient is carried out cervical dilatation, the PSM of 7-10cc was filled in the cavity of uterus.The embryo is moved grow conduit and remove after, import traditional metroscope and carry out endoscopy and need not connect filling system.After finishing direct development, utilize a kind of perfusion of expanding solution to carry out traditional uteroscopy.
Result-the cavity of uterus of slightly being expanded when inserting by viscosity PSM is detected easily with the panorama endoscopy.The viscosity of PSM prevents that also it from mixing with the blood that is derived from the uterine mucosa layer, and this will have fuzzy image.In 1 and 3 cases, identify the sub-mucosal fibroids of polyp and protrusion respectively.In a case, identify a kind of unexpected adhesion.In 2 remaining cases, do not see significant condition of illness.Procedural ground is along with the rising of PSM temperature and reach normal body temperature (after 3 minutes), the expansion forfeiture of viscosity and cavity of uterus, thereby the probability of the further endoscopy video picture of cavity of uterus that terminated.In all cases, later conventional uteroscopy has been confirmed endoscopy's discovery.
The video picture of discussion-whole cavity of uterus is good, allows to detect completely and the condition of illness that is present in all cases is carried out positive identification.In all cases, take pictures and find with record.In all cases, obtained affirmation by the operation temper palace spectroscopy of and then carrying out subsequently.Known to we whole, this has represented for the first time at the example that does not carry out panorama (and noncontact) uteroscopy constantly under the situation of perfusion or expansion solution or gas.
Conclusion-these results verifications the dabbling probability of persistence of using a kind of PSM not need a kind of inflation fluid or gas to obtain the cavity of uterus endoscopy and develop.This innovation has advanced the clinic endoscopy's in reform uterus potentiality.
In the office hysteroscopy that will under the situation that does not have cervical dilatation (it will minimize the discharge of undesirable medium) and anesthesia, carry out a kind of prototype medium is tested.
Embodiment 3: positive and negative radiography uterine gel
A kind of negative contrast glue will be particularly suitable for strengthening the ultransonic contrast in uterus.Such negative medium can promote the diagnosis and/or the ultrasonic expression of uterus condition of illness such as sub-mucosal fibroids, endometrial polyp, endometrium adhesion (cicatrix).Potentiality ground, negative gel can allow part or all of list or both fallopian tubes are carried out imaging.
The uterus of contact progesterone or progestogen, as the existence of following oral contraceptive may prolong glue are because progesterone and progestogen have the loose characteristic of Utero-.With seeking the negative contrast of other possible application, comprise for example by nuclear magnetic resonance and CT scan with other form of enhancing uterus and fallopian tube imaging.
Opaque contrast medium also will be useful.A kind of positive contrast dosage form may be by the positive ultrasonic contrast characteristic that obtains it through the bubble of calibration or ultrasonic-refraction granule such as microsphere, big-polysaccharide/starch etc.
And have other positive ultrasonic contrast product as the situation of Echovist, a kind of positive contrast heat-sensitive glue according to the present invention will be particularly useful to the development of oviducal proximal part.Yet opposite with existing product, our positive contrast hysterography glue also can carry out the evaluation and test of inotropic physiology of uterus and fallopian tube unit and pathophysiology.Utilize for example a kind of embryo transfer catheter to be positioned over the interior positive gel of cavity of uterus, can monitor to oviducal accurate displacement by the fallopian tube passage of evaluation air particles or other material, described air particles or other material retention are to give the echo property of glue.Can carry out various existing tests and determine that the best size of bubble or microgranule is so that the transmission of evaluation sperm.
The possible application of other of positive contrast gels will be conspicuous, comprise the various forms that is associated with negative gel, so that the development of the in utero tolerant retrograde transmission of enhancer.The possible application of the ultra sonic imaging of tool positive enhanced contrast comprises the associated symptom of inspection and treatment and dyscinesia uterina, as endometriosis or dysmenorrhea, and various forms of still inexplicable at present fertility Issue.
Diagnostic uterine gel (positive or negative radiography) will be designed to not have fetal toxicity.After check pH, the osmolarity physical characteristic relevant with other, will be in 2-cell mouse embryo system the fetal toxicity of tested media, if think and be necessary, in people's embryo system (as existing) in Sweden.There is not fetal toxicity will allow the doctor to use this uterine gel to carry out the functional functional test of uterus and fallopian tube, as the contractility function in test uterus.This comprises retrograde contractility, in uterus luteal phase during static and the normal general discharge direct motion contraction early stage follicular phase (menstruation) during of test when ovulation.If this glue can not be overall safety to the gravid woman, will test to determine the Secure Application in non-gravid woman it can not influence fertility on the contrary.We wish that this brood lac preparaton that can easily carry out is to make any Secure Application in two kinds of approach.
Embodiment 4: the present invention is used for the basic indication that uterine ultrasound is checked
The spy of medium manages the relative expansion that characteristic (as solid, semisolid or glue sample) permission produces cavity of uterus, only is a kind of " void " chamber under its normal condition, thereby has improved the imaging on its surface.How the character of this medium is able to practical application for it is necessary.Solid/semisolid character allows cavity of uterus to keep expanding relatively reaching a period of time, is enough to allow to finish ultrasonic examination.This medium liquefaction or disengaging of other subsequently allows it as any other liquid, the spontaneous discharge from the uterus as menstrual blood.
The echo property of this medium (both echo property or " negative contrast " or enhanced echo property or " positive contrast " that weakens) has strengthened the radiography of surrounding structure (endometrium and myometrium), is depicted as various ghosts on ultrasonic.
The raising of uterus and oviducal picture quality thus available from:
1. the expansion of cavity of uterus during checking allows the abundant retention of contrast agent simultaneously.
2. in cavity of uterus, use a kind of negative contrast medium (black) or opaque contrast medium (white) to strengthen radiography.
The present invention will be particularly suitable for checking the uterus, for example, and in the situation below:
1. identify anatomical pathologies such as metropolypus and/or the submucous fibroid that is present in the cavity of uterus.
2. identify oviducal anatomical pathologies and determine their opening (particularly using " positive " uterus to change contrast media mutually).
3. the uterus and the oviducal functional condition of illness that are associated with the abnormal patterns of contractility and the tolerant displacement of intrauterine of evaluation comprises
A) retrograde contraction that later stage follicular phase and defective sperm transmission and infertile/low pregnant property is associated unusually with
B) in menstrual phase when the contraction abnormalities that the uterus is contracted in when promoting to bring into play central role in the tolerant emptying of intrauterine (menstrual blood), it may cause the hemorrhage and endometriosis of antidromicity, or associated.
4. the perfusion of carrying out diagnostic uteroscopy and not needing liquid that continue or frequently or gas mixture allows the real contactless uteroscopy without gas or fluid drip with the expansion cavity of uterus.
5. the operation format of the uterus imaging except ultrasonic, for example hysterosalpingography (HSG), CT (X ray computer aided transverse tomography) scanning and MR imaging method.For HSG, the mixture that changes contrast agent and a kind of X-ray contrast solution (iodo or other) mutually can make the doctor need not be blown into solution, but allows solution directly amass in cavity of uterus.
Embodiment 5: the present invention is applied to the organ except that the uterus
The present invention will be applicable to the organ of inspection except the uterus, for example, and in following state:
1. as the contrast enhancer (male or negative) of the imaging of organ except uterus and fallopian tube, provide radiography during checking to strengthen the persistency of characteristic.
2. provide temporary expansion to carry out the imaging of normal body cavity, as hole or unusual body cavity, as fistula and or other cavity.
3. as with ultrasonic or other medical imaging form, the contrast enhancer of detecting other body cavity as CT scan, nuclear magnetic resonance and X-ray.
4. allow at normal or unusual body cavity, as the endoscopy evaluation and test of fistula the inside.
Embodiment 6: the application that other of medium of the present invention is possible
The present invention also can be used for the combination with the contrast media of other form.For example, this medium can be combined with the x-ray contrast agent of iodine and other form.This combination will be provided at body cavity or tissue lumen, as the existence of the prolongation in cavity of uterus and the fallopian tube, and the expansion in these chambeies and the perfusion that do not need to keep a kind of external pressure source and constantly carry out gas or liquid.
Those skilled in the art in the invention's level is all being represented in any He all publications mentioned in this manual and patent application.As quoting each each other publication or patent application as a reference, quote the mentioned all publications of this paper and patent application as a reference at this.
Be appreciated that the present invention is not limited to the concrete form that this paper is illustrated and describe.Therefore, all can from this paper carry out open by those of ordinary skills, or the normal experiment that carries out thus and the useful improvement that obtains easily all is considered within the defined the spirit and scope of the present invention as appending claims.
Claims (30)
1. medical imaging compositions that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, it comprises a kind of medium enhancing image, that change viscosity with initial viscosity or denseness, in in described medium is imported into body cavity or tissue lumen or afterwards, be enough in the chamber, keep original position to reach one period that is enough to finish imaging operation basically, wherein said composition has viscosity or the denseness that weakens subsequently, thereby this viscosity or denseness are fully weakened and allow this medium to be able to easily to discharge from the chamber or to remove.
2. the described compositions of claim 1, wherein said medium have the compositions of making and are suitable for being used in the characteristic of transvaginal sonography in checking.
3. the described compositions of claim 1, wherein said medium are corresponding to the specific change of the temperature of said composition and liquefy or reduce viscosity.
4. the described compositions of claim 2, wherein said medium provides the enhancing of negative contrast.
5. the described compositions of claim 3, wherein said medium provides the enhancing of positive contrast.
6. medical imaging compositions that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, it comprises a kind of medium that strengthens the transformation phase of image, wherein this medium
(a) in importing body cavity or tissue lumen or begin afterwards to be solid, semisolid or colloid, thereby during imaging operation, do not need to use constantly or continually this medium, and
(b) liquefy over time subsequently or weaken viscosity, thereby it can be discharged from the chamber or remove easily.
7. the described compositions of claim 6, wherein said medium have the compositions of making and are suitable for being used in the characteristic of transvaginal sonography in checking.
8. the described compositions of claim 6, wherein said medium are corresponding to the specific change of the temperature of said composition and liquefy or reduce viscosity.
9. the described compositions of claim 7, wherein said medium provides the enhancing of negative contrast.
10. the described compositions of claim 8, wherein said medium provides the enhancing of positive contrast.
11. a medical imaging compositions that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, it comprises a kind of medium that strengthens image, wherein this medium
(a) thus have enough viscosity it does not need to use constantly or continually this medium during imaging operation, and
(b) after finishing the time enough of imaging operation, from the chamber, discharge easily or remove.
12. a kind of polymer that provides initial viscosity to reach some times when using and different viscosities is provided corresponding to variation of temperature subsequently is provided for the described compositions of claim 1, wherein said medium.
13. the described compositions of claim 12, wherein the viscosity of polymer is weakened along with the rising of temperature.
14. the described compositions of claim 1, wherein said compositions further comprises one or more adjuvants or therapeutic agent.
15. the described compositions of claim 14, wherein said adjuvant or therapeutic agent comprise a kind of anti-infective or a kind of radiation opacifying agent.
16. one kind is carried out the medical imaging method of operating to body cavity or tissue lumen, comprises that (a) inserts the described compositions of claim 1 in the chamber, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the chamber subsequently.
17. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 1 in the uterus, (b) check, and (c) removes or allow compositions to discharge from the uterus subsequently.
18. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 3 in the uterus, (b) check, and (c) removes or allow compositions to discharge from the uterus subsequently.
19. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 4 in the uterus, (b) operate, and (c) removes or allow compositions to discharge from the uterus subsequently.
20. one kind is carried out the medical imaging method of operating to body cavity or tissue lumen, comprises that (a) inserts the described compositions of claim 6 in the chamber, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the chamber subsequently.
21. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 4 in the uterus, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the uterus subsequently.
22. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 8 in the uterus, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the uterus subsequently.
23. one kind is carried out the method that transvaginal sonography is checked, comprises that (a) inserts the described compositions of claim 9 in the uterus, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the uterus subsequently.
24. one kind is carried out the medical imaging method of operating to body cavity or tissue lumen, comprises that (a) inserts the described compositions of claim 11 in the chamber, (b) carry out imaging operation, and (c) removes or allow compositions to discharge from the chamber subsequently.
25. the image amplified medium application in the compositions of producing a kind of medical imaging method that is used for relating to a kind of body cavity or tissue lumen, wherein said medium
(a) be imported in body cavity or the tissue lumen or beginning to viscosity afterwards, thereby do not needing to use constantly or continually this medium, and
(b) liquefaction or reduce viscosity after being enough to carry out the time period of this formation method subsequently, and from the chamber, discharged or easily remove.
26. the image amplified medium application in the compositions of producing a kind of medical imaging method that is used for relating to a kind of body cavity or tissue lumen, wherein said medium
(a) importing in body cavity or the tissue lumen or beginning afterwards to be solid, semisolid or colloid, thereby do not needing to use constantly or continually this medium, and
(b) liquefaction or reduce viscosity after a period of time subsequently, and from the chamber, discharged or easily remove.
27. the image amplified medium application in the compositions of producing a kind of medical imaging method that is used for relating to a kind of body cavity or tissue lumen, wherein said medium
(a) begin to have enough viscosity, thereby it does not need to use constantly or continually during operation, and
(b) after being enough to normally to finish the time of this formation method, easily being discharged or removed subsequently.
28. a preparation that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, wherein said preparation is a kind of image amplified medium, this medium
(a) importing in body cavity or the tissue lumen or beginning to viscosity afterwards, thereby do not needing to use constantly or continually this medium, and
(b) liquefaction or reduce viscosity after being enough to carry out the time period of this formation method subsequently, and from the chamber, discharged or easily remove.
29. a preparation that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, wherein said preparation is a kind of image amplified medium, this medium
(a) importing in body cavity or the tissue lumen or beginning afterwards to be solid, semisolid or colloid, thereby do not needing to use constantly or continually this medium, and
(b) liquefaction over time subsequently or reduction viscosity, and from the chamber, discharged or easily remove.
30. a preparation that is used for relating to the medical imaging method of a kind of body cavity or tissue lumen, wherein said preparation is a kind of image amplified medium, this medium
(a) thus have enough viscosity it does not need to use constantly or continually, and
(b) after being enough to normally to finish the time of this formation method, easily being discharged or removed.
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| US37864002P | 2002-05-09 | 2002-05-09 | |
| US60/378,640 | 2002-05-09 | ||
| US60/428,145 | 2002-11-21 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103620386A (en) * | 2011-05-13 | 2014-03-05 | 贝克曼考尔特公司 | Method and apparatus for diagnosing blood parasites |
| CN106573089A (en) * | 2014-05-16 | 2017-04-19 | 奥创斯特公司 | Phase-shifting formulations |
| CN110246135A (en) * | 2019-07-22 | 2019-09-17 | 新名医(北京)科技有限公司 | Monitor Follicles method, apparatus, system and storage medium |
| CN113041404A (en) * | 2021-03-19 | 2021-06-29 | 北京化工大学 | Preparation method of medical catheter with ultrasonic imaging capability based on hydrophobic modified porous starch and product thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108778346B (en) * | 2016-01-10 | 2022-02-11 | 斯迈索尼卡股份有限公司 | Ultrasound gel with improved viscosity and stability |
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2003
- 2003-05-08 CN CNB038154749A patent/CN100467067C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103620386A (en) * | 2011-05-13 | 2014-03-05 | 贝克曼考尔特公司 | Method and apparatus for diagnosing blood parasites |
| CN106573089A (en) * | 2014-05-16 | 2017-04-19 | 奥创斯特公司 | Phase-shifting formulations |
| CN110246135A (en) * | 2019-07-22 | 2019-09-17 | 新名医(北京)科技有限公司 | Monitor Follicles method, apparatus, system and storage medium |
| CN113041404A (en) * | 2021-03-19 | 2021-06-29 | 北京化工大学 | Preparation method of medical catheter with ultrasonic imaging capability based on hydrophobic modified porous starch and product thereof |
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