CN1132557C

CN1132557C - Improved method for targeted topial treatment of disease

Info

Publication number: CN1132557C
Application number: CN998110493A
Authority: CN
Inventors: H·C·蒂斯; T·斯科特; J·斯莫里科; E·A·沃奇特; W·费舍尔
Original assignee: Photogen Inc
Current assignee: Photogen Inc
Priority date: 1998-08-06
Filing date: 1999-08-02
Publication date: 2003-12-31
Anticipated expiration: 2019-08-02
Also published as: JP2002522111A; MXPA01001336A; TW396030B; AU5391799A; EP1109506A1; IL141273A0; AU750633B2; CA2339384A1; CN1317952A; HK1039555B; CA2339384C; HK1039555A1; BR9912773A; KR20010072307A; AR021750A1; EP1109506A4; WO2000007515A1

Abstract

A method and apparatus for topical treatment of diseased tissue, including topical or systemic application of a PDT agent to diseased tissue, followed by topical application of light (24).

Description

The device of targeted topial treatment of disease

The present invention is the part continuation application of the USSN 08/739,801 of application in 1996 10 about 30 days.

The present invention relates to use optical dynamic therapy (PDT) and PDT medicine topical therapeutic to organize the especially method and apparatus of illing tissue.More particularly, the present invention relates to use the method and apparatus that the PDT medicine uses up for the illing tissue part then to illing tissue part or whole body.

People have developed PDT and have been used for the treatment of cancer and other diseases, can limit treatment get involved the infringement that causes and alleviate potential concurrent infringement normal, non-illing tissue.The cardinal principle of PDT comprises that selectivity is used or selectivity is taken in photosensitive drug to illing tissue and directly use active light at the position.The PDT medicine generally be general (for example) by intravenous injection or oral or by the part directly be applied in illing tissue (as, by the part with cream, ointment or spray) use.After the administration (after general 30 minutes to 72 hours), active light is used for disease location, local activation medicine and damages illing tissue.General direct sunshine makes according to the position and uses up, and perhaps uses fibre-optic catheter or similar device that luminous energy is transported to interior location.

It is main medicine for main medicine or part or whole body use psoralen that most popular PDT therapy use to be foretold quinoline based on whole body.The fore-telling quinoline is that the example of master's medicine comprises Bu Feier sodium (PHOTOFRIN ), blood fore-telling quinoline derivant (HPD) or SnET ₂PHOTOFRIN  is one of medicine of current FDA permission.Foretell quinoline and be main medicine generally from the compound mixture of the material of natural or synthetic preparation.Foretelling quinoline is that the main most compositions of medicine are lipophilic.Because this lipotropy, foretelling quinoline is that main medicine has demonstrated the slight tendency that preferably is accumulated in some tumors.But this class medicine is compared the still low people that can't allow to the targeting of illing tissue and is accepted (promptly arriving 2-10X greatly with respect to the absorption in the normal structure illing tissue) with the absorption of normal structure.

In addition, thus owing to have that treatment is positioned at the demand of the cancerous tumour of depths to medicine that can be compatible with the active light of hypersynchronous, to foretell quinoline be main medicine so at first developed.For example, generally foretelling quinoline with the photoactivation of the wavelength of 600-750nm is main medicine, and this light can penetrate into 1cm or darker in the tissue.Compare, the light that is lower than the 600nm wavelength will only penetrate into the degree of depth less than 1cm.

However, great majority fore-telling quinoline is that the dark toxicity of master's medicine still is higher.Dark toxicity is the cytotoxicity that does not have under the active light existence.When needing the medicine of high dose for effective treatment particular tissues, the illumination meeting produces only a spot of Cytotoxic increase.Say that more specifically the checkout time of whole body is promptly behind the drug administration, skin and other outside organizations occur significant drug level during, can extend to the several months from several weeks, for fear of serious skin irritation and other complication, this forces the patient to be avoided the long term being exposed under light or the sunlight.The whole body administration also need have 30 minutes to 72 hours interval between drug administration and photoactivation, this has prevented the probability of illing tissue being treated at once in case measure this class illing tissue substantially.And, measure and treatment gastrointestinal disease such as Bart's thunder esophageal disease need at least two endoscopies to detect steps: step diagnosis, then take the PDT medicine after illumination treat illing tissue.

Between light and dark cell toxicity, there are not significant difference and most preferred low concentration commonly used need use high dose than PDT medicine.For example, need be with PHOTOFRIN  treatment adult male's dosage greater than the medicine of 100mg, only DO itself just is worth, more than 000.This heavy dose also can cause significantly the health tissues probability of (as the skin phototoxicity) that has side effects, and can keep several weeks.Because being main medicine, the fore-telling quinoline can be made the patient emit the very big danger of permeating the severe complication that produces by the tissue of this class NIR light based on the step of foretelling quinoline+NIR by approximately light (promptly near infrared ray (the NIR)) activation of 600nm wavelength.Complication comprises the perforation of esophagus of internal structure as the treatment esophagel disease, and this is because medicine not wishing in the health tissues layer except that the topical therapeutic position activates.

In addition, foretelling quinoline and be main PDT medicine realizes the cytotoxicity of photoactivation generally cell oxygen being converted into Cytotoxic single oxygen by II type mechanism.Because the content of cell oxygen can be used up easily in the activation process of II type PDT medicine, use the low intensive relatively illumination of this class medicine requirement, in order in the whole process of photoactivation, to make oxygen concentration keep enough, need to use long relatively illumination like this.For example, in PHOTOFRIN  treatment Bart thunder esophageal disease, light intensity generally must remain on 100-150mW/cm during treating ², needed 10-20 minute or longer illumination period.Many practitioners have been found that also II type medicine may comprise that for avoiding any the sanguimotor tissue of therapentic part changes between illumination period, thereby avoid the potential usefulness of available oxygen to be full of considerable.Therefore, thus carefully controlling illumination apparatus and step is crucial guarantee to carry suitable light intensity and do not influence tissue with influencing sanguimotor mode.

Bart's thunder esophageal disease is the best example of local disease, when it occur in be difficult to by the routine operation method near but use the approaching position of endoscopic catheters easily, PDT is suitable for this disease very much.This disease is the esophagus that the chronic acid backflow of stomach stimulates gastroesophageal junction, causes the outgrowth disease of epithelial tissue of esophagus.The patient who suffers from Bart's thunder esophageal disease has the obvious high-risk of the esophageal carcinoma of developing into.FDA has ratified PDT (with the PHOTOFRIN  of 630nm place light) and has destroyed Bart's thunder patient's hyperplastic tissue.Also can use similarity method to remove the esophagostenosis that causes by the esophageal carcinoma.

Use the conventional method of PDT treatment Bart thunder esophagus to show in cross section mode at Fig. 1 (a).Esophagus 10 has adjacent tissue surface 12 and remote organization surface 14.In the example shown in Fig. 1 (a), part esophagus 10 be health tissues 16 and in addition a part be illing tissue 18.Generally, the non-compliance balloon 20 that inserts in the esophagus is used for stablizing the tissue of receiving treatment., balloon usefulness gas or liquid filling avoid the expansion of esophagus thereby expanding into known radius (near the esophagus of filling).This expansion can cause that blood flow is restricted to therapentic part, and providing of oxygen can be provided during photoactivation in this blood flow restriction.Fiber optics inserts the center of balloon 20 and comes to provide uniform light intensity to balloon surface as light source 22.The external structure of balloon 20 can be formed or can is that the transparent material of exciting light is formed by the material of scatter activity light 24.

Can activate the PDT medicine on (on adjacent tissue surface 12) the tissue that is present in position, adjacent gas bulb from the light of balloon 20 surface scatterings.Because balloon 20 is non-compliances, so can assess the light intensity of balloon surface according to the knowledge of the light scattering characteristic of balloon geometrical property and light source 22.Fiber optics diffuser tip is an example of this light source.But, because the outer surface of balloon 20 generally can not accurately conform to the shape of esophagus, thus it can not accurate assessment adjacent tissue surface 12 around the light intensity of each point.And the 12 light districts that exist are uneven on adjacent tissue surface, for example since the inhomogeneous or light source 22 of the light scattering characteristic of light source 22 at the errors present of esophagus 10, uneven treatment is possible.In extreme case, this inhomogeneous treatment can damaging tissue and is enough to cause the hypertrophy and the death of tissue.

Shown in Fig. 1 (b), the PDT medicine that activates in esophagus through illumination will form treatment region 26, treatment region generally comprise illing tissue 18 among Fig. 1 (a) Zone Full and can be radially and expand to the enough distances that exceed illing tissue 18 edges on every side, in fact, medicine activates the formation that used NIR light can cause treatment region, this treatment region will expand to adjacent tissue surface 12 from esophagus 10 to the remote organization surface 14 distances enough far away.This is that NIR light exists tangible systemic concentrations than the result of big length of penetration feature and at the health tissues medicine.Under extreme case, the expansion of this treatment region tissue that can impair one's health is enough to cause hamartoplasia and death.

The example that uses PDT to treat surface damage describes many shortcomings of current method and apparatus in detail, and for example: (1) because medicine needs higher dosage, it is expensive that whole body uses medicine; (2) whole body uses medicine can cause the allergy of the outer health tissues of required treatment region; (3) whole body uses medicine can cause long skin photosensitivity; (4) thus whole body uses need be between medical diagnosis on disease and the disease treatment bigger interval of medicine reach illing tissue simultaneously less than surrounding health tissue as medicine; What (5) whole body used that medicine can require the restricted control medicine of PDT user transports position and drug level; (6) owing to the uneven distribution of medicine in illing tissue, whole body uses medicine can cause uneven treatment; (7) use II type medicine to need to activate slowly and for a long time and avoid exhausting of oxygen; (8) use II type medicine to need careful tissue manipulation to avoid the restriction of blood flow and the oxygen depletion that in organizing the illumination process, produces; (9) use II type medicine, stimulate the light time, in most local uses, can cause the unnecessary treatment degree of depth, the health tissues around the otherwise impact when being used in combination NIR.

So, the purpose of this invention is to provide and improve new method and the device that uses PDT, increase the safety of effect and operation simultaneously and reduce medical expense.

The present invention relates to a kind of method and apparatus of topial treatment of disease, comprise to illing tissue part or whole body and use the PDT medicine, then local light shines.Generally, this method comprises the step of using PDT medicine formation treatment region to illing tissue; Remove excess drug; And should use up treatment region and activate the medicine relevant with diseased tissue.This light is penetrated into treatment region and drops to the outer pharmaceutically active of treatment region minimum simultaneously.

In a preferred embodiment, the PDT medicine is rose-red.

In another embodiment, only the PDT medicine is applied directly to treatment region.But whole body uses the PDT medicine.

In yet another embodiment, thus activate light wavelength by suitable selection and control the degree of depth that activates the PDT medicine and avoid activating the medicine that is present under the health tissues.

In other embodiment, before using the PDT medicine, diagnose illing tissue.

In another embodiment, substituting different diagnosis with one step (as endoscope) and treat step at short notice can efficient diagnosis and treatment focus.

In yet another embodiment, treatment rate is not limited by oxygen dependence mechanism.

In another embodiment, heating can increase the activated effect of medicine to treatment region.

In other embodiments, carry exciting light by " balloon " or other conveyer devices that are positioned at disease location.

In yet another embodiment, method of the present invention can be treated the gastrointestinal disease.

Method of the present invention also can be used in the disease in the treatment blood circulation blood vessel.

The invention still further relates to the device of topical therapeutic illing tissue.

So, the present invention relates to treat the method and apparatus of Bart's thunder esophageal disease and other diseases, the device of this method improves light and carries the uniformity, improves safety and effect and reduce the PDT cost.

In the preferred embodiment of describing, accompanying drawing as a reference, wherein:

Fig. 1 (a) has shown that the cross section of esophagus is used for illustrating the conventional method that uses PDT treatment Bart thunder esophageal disease;

Fig. 1 (b) has shown the treatment region of Fig. 1 (a) method;

Fig. 2 (a) describes the example that the present invention treats the embodiment of ill esophageal tissue in detail;

Fig. 2 (b) describes another example of Fig. 2 (a) embodiment in detail;

Fig. 2 (c) describes another example of Fig. 2 (a) embodiment in detail;

Fig. 3 (a) describes the example of another embodiment of disease in the treatment blood circulation blood vessel in detail;

Fig. 3 (b) describes another example of Fig. 3 (a) embodiment in detail, and wherein the PDT medicine directly is applied in the illing tissue.

Method and apparatus of the present invention can be used for the improvement treatment of various dermatosiss such as psoriasis or skin carcinoma and intravital illing tissue such as digestive tract or respiratory tract disease.The present invention also can be used for the treatment of other regions of anatomy and comprise that abdomen is interior, it is interior to swallow, heart is interior, circulation is interior, brain is interior and reproductive tract.

Generally, method of the present invention comprises one or more the following steps.Beginning is used the mensuration of tissue examination for example or the automatic fluorescent characteristic by illing tissue or is absorbed and diagnose the illness by measuring indicator such as fluorescent dye or the selectivity of PDT medicine in this class illing tissue.Afterwards, thus use part or the whole body preparation of the required PDT of q.s to cover, be full of or saturated illing tissue to illing tissue.Make medicine cover, be full of or other make medicine illing tissue become have the active extensive accumulation phase after, clean or the unnecessary medicine of flushing disease location, light activates the medicine relevant with diseased tissue thereby use almost uniformly to disease location.

In order to treat surperficial illing tissue, thus preferably select light wavelength make light to illing tissue's infiltration but outside can be illing tissue the irradiation under the health tissues drop to minimum thoroughly.For example, can use spectral regions can provide the order of magnitude at the visible light of 400-600nm is several millimeters or littler shallow length of penetration.Use this light can provide the activated effect of surperficial illing tissue Chinese medicine simultaneously the latent effect of harmful photosensitivity reaction to be dropped to minimum.Preferably, use laser.It can be carried by optical fiber tube.Perhaps available direct sunshine is according to carrying light.Other alternate light-source structures and conveyer device comprise fibre bundle, in have the optical waveguide of core and the waveguide of filling liquid in vain.Alternate light source comprises the lamp of light dispersion diode, miniature laser, monochrome or continuous laser and generation exciting light, and continuous wave or pulse laser or lamp.Monochromatic light or bi-coloured light exciting method can be used for the activation of medicine.The more detailed explanation of this stimulating method provided in the common patent application serial number of transferring the possession of 08/739,801 in October, 1996, and this patent application is cited as list of references at this.

And the order of time and use medicine and light also is transformable.For example, the Therapeutic Method that can repeat one or many use medicine and light is removed remaining illing tissue.Further, concerning some used, it also was useful increasing the use of medicine and the interval between the light treatment.In addition, thus can then use the PDT medicine behind the diagnosis algorithm, the step of removing unnecessary medicine and illumination only realizes diagnosis and the method for the treatment of with a step at once.If use the PDT drug absorption to diagnose or measure illing tissue, can use the step of exciting light behind the diagnosis algorithm at once.On the other hand, can between diagnosis and PDT treatment, uncertain delay be arranged.

Preferred use is rose-red as PDT or photosensitive drug, because it is not expensive and nontoxic, human safety records with confirmation, has significant inner liposoluble characteristic, have the mechanism activation that I type and II type PDT react and therefore can not relied on oxygen by the I type, and just have strong phototoxicity with the photoactivation between the 500nm to 600nm.Because it does not rely on the reaction of oxygen, rose-red and high-intensity photostimulation is compatible mutually, and it is that main medicine has reduced treatment time with respect to foretelling quinoline.More particularly, be to use the photoactivation between the 500nm to 600nm rose-red ideally, this is enough to the activated surface diseased tissue and has almost been avoided the activation health tissues.The example of this PDT medicine is with the suitable fat-soluble carrier such as the rose-red solution of 1-capryl alcohol or liposome formulation.

On the other hand, can use other PDT medicine to comprise I type or II type medicine.The example of the PDT medicine of this class standard comprises the psoralen derivant; Foretell quinoline and blood and foretell quinoline derivant; The chlorin derivant; Phthalocyanine derivates; The rhodamine derivant; Coumarin derivative; Benzo phenoxazine derivant; Chlorpromazine and chlorpromazine derivant; Chlorophyll and sterilization phyllins; Phaeophorbide a (Pheo.a); Merocyanine 540 (MC 540); Vitamin D; 5-amino-levulic acid (ALA); Photosan; Phaeophorbide-a (PH-a); The blue derivant of phenoxazine Nile comprises various phenoxazine dyestuffs; PHOTOFRIN; Benzo is foretold the acid of quinoline derivant list; SnET ₂And Lutex.The present inventor believes that all PDT medicines current and future all can act in method and apparatus of the present invention.

In addition, the invention is not restricted to use a kind of PDT medicine.That is to say, in Therapeutic Method, can use more than one PDT medicine.

In another embodiment, the used PDT medicine of the present invention comprises at least one targeting moiety.The example of this targeting moiety comprises DNA, RNA, aminoacid, protein, antibody, part, hapten, carbohydrate receptor or complexing agent, lipid receptor, liquid receptor or complexing agent, protein acceptor or complexing agent, chelating agent and the carrier of sealing.Can use these target parts to improve the selectivity that medicine is transported to illing tissue, and can work by medication combined with photosensitive PDT (for example the carrier that the PDT medicine is formed with targeting moiety is sealed) or by combine (for example PDT medicine and targeting moiety covalent bond) with photosensitive PDT medicine.

In another embodiment, illing tissue is directly used the PDT medicine.Directly local the use has many advantages.Especially, it provides the targeted drug to the single-minded improvement of illing tissue, shorten the required incubation period between administration and the illumination and therefore shortened treatment cycle, almost eliminated the photosensitive latent effect of whole body, reduce the consumption of medicine, and reduced the side effect latency that causes because of this drug exposure.This medicine preferably uses with locally sprayed or flushing.Behind brief accumulation period (generally being no more than 30 minutes), with liquid such as water or normal saline washing tissue surface to remove unnecessary medicine.After the flushing, the visible light illumination disease location between the most handy 400nm to 600nm activates the residual drug that links with illing tissue.Can use up the part as mentioned above.

On the other hand, also can use the PDT medicine by whole body.For example, this use can be by intravenous injection stomach function regulating canal drug administration (as by using the tablet or the liquid preparation of PDT medicine).

In yet another embodiment, by hyperpyrexia treatment region is heated and increase the PDT effectiveness.For example, perhaps use ultrared energy light exposure treatment position simultaneously, heat can be provided by using the transparent heating cushion between liquid, illumination source and the tissue that heated in the illuminating balloon.

The example that has shown some embodiments of the invention among Fig. 2 (a), 2 (b) and 2 (c) with cross section form.

Fig. 2 (a) describes in detail and uses the treatment of non-compliance balloon 20 illumination apparatus to ill esophageal tissue.Treatment region 30 is confirmed in beginning.This step can be for example differentiated by the visible light in splanchnoscopy esophagus and illing tissue district or spectrum and carries out.This class is differentiated and is comprised other visible indication of measuring tissue variation or disease, measures automatic change in fluorescence, perhaps measures the absorption in illing tissue of PDT or other drug.Confirmed after the treatment region 30, used the PDT medicine for the illing tissue that confirms.This medicine also can use by nozzle or the direct spraying of other devices that whole body uses or more preferably be used in the esophagus far-end to provide.Then clean or pass through and remove unnecessary medicine from this position with liquid wash by for example natural whole body.

Thereby then transparent non-compliance balloon apparatus 20 is inserted esophagus and estimate treatment region 30.Thereby the balloon 20 with gas or the non-compliance of liquid filling is set up the required diameter of measuring in advance to the pressure of measuring in advance.Then visible light 24 usefulness light sources 22 as the optical fiber diffuser that is positioned at the balloon central shaft wall by balloon 20 radially evenly is transported to therapentic part.

In addition, balloon 20 can enough disperse medium such as the dilute solution of inner lipid fill, thereby improved the uniformity of the light intensity that balloon surface transports.And such material be formed or be comprised to balloon 20 also can by such material, promptly disperses the material of the light 24 that balloon surface transports, thereby further improve the uniformity of the light intensity that balloon surface transports.This class examples of substances comprises natural translucent material such as latex; The polymer that comprises the granule scatterer; Or has a polymer of rough surface.

Among the embodiment that describes in detail in Fig. 2 (a), the intensity of operating light source 22 with the concentration of measuring in advance arrives the persistent period of measuring in advance, and this depends on the required light intensity and the light quantity of the filling radius and the balloon surface of non-compliance balloon 20.

Fig. 2 (b) cross section has shown another example of this embodiment, wherein with the ill esophageal tissue of non-compliance balloon 40 treatments that enlarges.In this embodiment, after the affirmation illing tissue, use the PDT medicine for again the illing tissue that confirms.Remove the unnecessary medicine in this position subsequently.

Thereby then transparent non-compliance balloon apparatus 40 is inserted esophagus and estimate treatment region 30.Thereby, eliminate the folding of esophagus surface and form more thus that uniform tissue surface 12 is used for illumination with non-compliance balloon 40 expansion or the slight expansion esophaguses of gas or liquid filling.Measure stuffing pressure to set up the radius of filling balloon.The optical fiber diffuser that uses light source 22 then as be positioned at the balloon central shaft pass the balloon wall equably radial delivery visible light 24 to therapentic part.

In addition, balloon 40 can enough disperse medium such as the dilute solution of inner lipid fill, thereby improved the uniformity of the light intensity that balloon surface transports.And such material be formed or be comprised to balloon 40 also can by such material, promptly disperses the material of the light 24 that balloon surface transports.This class examples of substances comprises natural translucent material such as latex; The polymer that comprises the granule scatterer; Or has a polymer of rough surface.

Mensuration is used to fill the pressure of balloon and is used for setting up the operative radius of filling balloon, to a certain degree operating the intensity of light source 22, thereby this degree is the required light intensity and the light quantity of selecting to transport balloon surface according to the operative radius of the non-compliance balloon 40 of filling.Preferably esophagus district folding of treatment dropped to minimum in another embodiment and thereby the esophagus that significantly do not expand is avoided potential narrow or other nonspecific stimulations of esophageal tissue with surface pressing.

Another example that has shown this embodiment in Fig. 2 (c) cross section is with the ill esophageal tissue of non-compliance balloon 50 treatments that enlarges.In this embodiment, after the affirmation illing tissue, use the PDT medicine for again the illing tissue that confirms.Remove the unnecessary medicine in this position subsequently.

Thereby then transparent non-compliance balloon apparatus 50 is inserted esophagus and estimate treatment region 30.Thereby, almost eliminated the uneven contact between esophagus surface and the balloon and formed thus more that the uniform tissue surface is used for illumination with gas or non-compliance balloon 50 fillings of liquid filling, expansion or slight expansion esophagus.Measure stuffing pressure to set up the roughly radius of filling balloon.The optical fiber diffuser that uses light source 22 then as be positioned at the balloon central shaft pass the balloon wall equably radial delivery visible light 24 to therapentic part.

In addition, balloon 50 can enough disperse medium such as the dilute solution of lactone fill, thereby improved the uniformity of the light intensity that balloon surface transports.And such material be formed or be comprised to balloon 50 also can by such material, promptly disperses the material of the light 24 that balloon surface transports.This class examples of substances comprises natural translucent material such as latex; The polymer that comprises the granule scatterer; Or has a polymer of rough surface.

Mensuration is used to fill the pressure of balloon and is used for setting up the operative radius of filling balloon.Like this, in this embodiment, to a certain degree operating the intensity of light source 22, thereby this degree is to select to transport the required light intensity and the light quantity of balloon surface according to the operative radius of the non-compliance balloon 50 of filling.Preferably the folding minimum that drops in the esophagus district of treatment do not had remarkable expansion esophagus (thereby avoiding potential narrow or other nonspecific stimulations of esophageal tissue) in another embodiment with surface pressing.

In order to treat the angiopathy (as tremulous pulse or vein speckle) in the blood circulation, Fig. 3 (a) and 3 (b) describe preferred another embodiment of the present invention in detail.

In the specific embodiments of Fig. 3 (a), gastropore or use photosensitizer by intravenous injection.This drug accumulation forms treatment region 62 on illing tissue's blood vessel wall.Select this medicine to depend on the preferred concentration of the ill material that required treatment region exists.After main accumulated phase,, light 64 activates the medicine relevant with the disease material thereby being used for disease location.This application can realize by using optical fiber tube 66 or having the focal length, adjustment or the diffusion boundary similar installation that are used for the spatial control that light carries.Thereby this optical fiber tube 66 can directly be carried light 64 can the part to make to treatment region 62 and use up.Be penetrated into health tissues in order to reduce potential light, thereby preferably use spectral regions to realize several millimeters or still less shallow length of penetration at the visible light of 400-600nm.Use this class light can provide the active effect of surperficial ill material Chinese medicine simultaneously the potential hazard of deleterious photosensitization under the tissue to be dropped to minimum.

On the other hand, described in detail as Fig. 3 (b), the administration of photosensitizer can realize to the ill material in the treatment region 62 by locating direct drug application.Drug administration can realize at an easy rate that as capillary tube capillary tube is connected to and terminates near optical fiber tube 66 ends by delivery device 68, is used for carrying small amount of drug to form drug flow 70 or other flow, and directly arrives or near treatment region 62.In addition, this conveyer device 68 can be separated from optical fiber tube 66, is beneficial to independent each terminal of placing light delivery optical fiber pipe 66 and delivery device 68 thus.In other embodiments, give in the treatment region 62 after a small amount of photosensitizer of ill mass transport, after of short duration accumulated phase, make with light 64 to disease location and to activate the medicine relevant with the disease material.

In these embodiments, preferably the rose-red photosensitizer that is used as.Use the light between the 500nm to 600nm to activate ideally rose-red, this light is enough to activating surface disease material and almost avoids the activatory potential hazard of health tissues.And this medicine is compatible with high-intensity exciting light to be closed, and can reduce other drug such as II type PDT medicine required treatment time thus.

The description that is provided is the purpose in order to describe in detail just, is not in order to limit the application's invention, and the application's invention limits with following claim.

Claims

1. the device of a topical therapeutic illing tissue, it comprises; Be applied to the PDT medicine that forms treatment region in the illing tissue; Remove the device of unnecessary medicine; With the light source that activates treatment region PDT medicine, wherein light wavelength drops to the activity of the medicine outside the illing tissue minimum simultaneously thereby make light can penetrate into illing tissue in the 400-600nm scope.

2. according to the described device of claim 1, wherein can excite and activate medicine with monochromatic light.

3. according to the described device of claim 1, wherein excite and activate medicine with bi-coloured light.

4. according to the described device of claim 1, the selectivity that also contains by measuring indicator absorbs the indicator of diagnosing illing tissue.

5. according to the described device of claim 4, wherein indicator is selected from fluorescent dye and PDT medicine.

6. according to the described device of claim 1, wherein the PDT medicine is rose-red.

7. according to the described device of claim 6, the about 500-600nm of light wavelength wherein.

8. according to the described device of claim 1, also comprise more than one PDT medicinal application to illing tissue.

9. according to the described device of claim 1, wherein the PDT medicine comprises targeting moiety.

10. according to the described device of claim 9, wherein targeting moiety is selected from down in the group: DNA, RNA, aminoacid, protein, antibody, part, hapten, carbohydrate receptor or complexing agent, liposome or complexing agent, protein acceptor or complexing agent, chelating agent and the carrier of sealing.

11., wherein the PDT medicine is applied directly in the illing tissue according to the described device of claim 1.

12. according to the described device of claim 1, wherein whole body is used the PDT medicine.

13., also comprise heat is used for the treatment of the activity that the district increases medicine according to the described device of claim 1.

14., wherein in the ballon catheter device, heat by heated liquid according to the described device of claim 13.

15. according to the described device of claim 13, wherein with transparent heating cushion heating.

16., wherein carry out illumination by the ballon catheter device according to the described device of claim 1.

17. according to the described device of claim 16, wherein the ballon catheter device is non-compliance.

18. according to the described device of claim 17, the ballon catheter device of the non-compliance that wherein extends is so that actual extended treatment district.

19. according to the described device of claim 16, wherein ballon catheter is a compliance.

20. according to the described device of claim 16, wherein ballon catheter is filled with astigmatic medium.

21. according to the described device of claim 16, wherein ballon catheter comprises astigmatic material.

22. according to the described device of claim 1, wherein direct sunshine is according to using up.

23. according to the described device of claim 1, wherein the light source of illumination is selected from following group: the laser and the pulse laser of fiber optics bundle, the hollow-optical waveguide of heart line, the waveguide of filling liquid, astigmatic diode, miniature laser, one-wavelength laser, continuous laser, lamp, continuous wave.

24. according to the described device of claim 1, wherein the PDT medicine is a kind of standard P DT medicine at least.