WO1999056625A1 - Method and apparatus for estimating cerebral perfusion pressure - Google Patents
Method and apparatus for estimating cerebral perfusion pressure Download PDFInfo
- Publication number
- WO1999056625A1 WO1999056625A1 PCT/GB1999/001321 GB9901321W WO9956625A1 WO 1999056625 A1 WO1999056625 A1 WO 1999056625A1 GB 9901321 W GB9901321 W GB 9901321W WO 9956625 A1 WO9956625 A1 WO 9956625A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cpp
- blood flow
- flow velocity
- doppler
- velocities
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/06—Measuring blood flow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Clinical applications
- A61B8/0808—Clinical applications for diagnosis of the brain
Definitions
- This invention relates to a method of and/or apparatus for estimating Cerebral Perfusion Pressure (CPP) and, in particular, to a method of and/or apparatus f or estimating CPP non- invasively.
- CPP Cerebral Perfusion Pressure
- ICP intracranial pressure
- ABP arterial blood pressure
- the invention pro vides a method of estimating cerebral perfusion pressure (CPP), said method including the steps of:
- said method further includes calculating the difference in CPP from the individual CPP measures derived from said blood flow velocities.
- the blood flow velocities are preferably measured non-invasively and in real time. Doppler ultrasonography is conveniently used.
- APBm is the time averaged arterial blood pressure
- FVd is the diastolic blood flow velocity
- FVm is the time averaged blood flow velocity.
- the invention provides a method of deriving, non-invasively, an estimate of cerebral perfusion pressure (CPP) said method including:
- the invention provides apparatus for providing an estimate of cerebral perfusion pressure (CPP), said apparatus including detection means for deriving measures o f blood flow velocity in the left and right middle cerebral arteries; and pressure assessment means operable to derive an estimate of cerebral perfusion pressure based on both of said measures of blood flow velocity.
- CPP cerebral perfusion pressure
- the apparatus preferably further includes transcranial Doppler insonation means operable to insonate sections of the left and right middle cerebral arteries.
- said Doppler insonation means includes a pair of Doppler ultrasound probes mounted on headgear engageable with the head of a patient.
- Said assessment means is preferably operable to derive the assessment of CPP by application of the algorithm:
- APBm is the time averaged arterial blood pressure
- FVd is the diastolic blood flow velocity
- FVm is the time averaged blood flow velocity.
- Figure 1 shows a diagram of the method used to provide an indication of CPP according to the invention.
- Figure 2 shows a block diagram of the app aratus used to perform the method.
- the present invention provides a method of obtaining bilateral estimates of cerebral perfusion pressure (CPP) and, from the two individual estimates, forming a composite measure of CPP from which considered decisions can be made as to the condition and treatment of the patient under observation.
- CPP cerebral perfusion pressure
- non-invasive esti mates are made according to techniques which have been shown to render acceptably accurate measures over a significant sample of patients. These non-invasive estimates are derived by applying an algorithm to wave forms of blood flow velocity produced using transcranial Doppler ultrasonography.
- blocks 5 and 6 represent the steps of obtaining a blood flow velocity plot using transcranial Doppler ultrasonography.
- One form of apparatus used to derive such wave forms is described below but others may be used.
- an algorithm is then applied to those from each side of the brain so as to derive individual estimates of CPP, as can be shown by blocks 7 and 8.
- Standard, software based, curve fo llowing techniques and frequency analysing techniques are used in the application of 20 the algorithm.
- the individual estimates of CPP may then be compared, as at 9, to form a composite estimate of CPP.
- APBm is the time averaged arterial blood pressure
- FVd is the diastolic blood flow velocity
- FVm is the time averaged blood flow velocity.
- the apparatus includes a pair of 10 probes 11a, l ib containing crystals configured to transmit and receive ultrasound.
- the probes may also include pre-amplifiers.
- We (Deltex Medical Limited) produce suitable 2MHz probes but suitable probes are also available from a number of alternative manufacturers including Scimed, Bristol, United Kingdom.
- the probes 11a, l ib are mounted on a headband (not shown) and aligned so as to insonate the left and right middle cerebral arteries.
- the probes 11a, l ib are driven by pulsed Doppler transmit and receive circuits 12a, 12b respectively. These are of conventional form.
- Signals from each of the circuits 12a, 12b are passed, via an analogue to digital converter, into a dual channel frequency analyser 13 which comprises digital signal processing circuits 14a, 14b to process signals received from the Doppler circuits 12a, 12b respectively, and a system board 15 for calculating individual measures of CPP from both left and right side, and for calculating the difference in CPP between left and right side.
- the individual measures of CPP are preferably calculated by application of the algorithm: ABPm*FVd/FVm
- APBm is the time averaged arterial blood pressure
- FVd is the diastolic blood flow velocity
- FVm is the time averaged blood flow velocity.
- Arterial blood pressure can be measured using a manual cuff or an arterial line inserted into, for example, radial or logis pedis arteries.
- the latter form of apparatus is more invasive but has the advantage of allowing continuous monitoring of APB.
- the composite estimate of CPP is derived by calculating the difference between the individual left and right side CPPs.
- the present invention at least in respect of the preferred form of apparatus de scribed herein, provides a method of and/or apparatus for continuously indicating CPP in real time which gives a wider and more useful range of information to the medical professional.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
Abstract
The present invention provides a method of non-invasively measuring cerebral perfusion pressure from a composite of individual blood flow velocities in the left and right side middle cerebral arteries. The velocity measurements are preferably obtained using Doppler ultrasonography and the left and right measurements are preferably averaged.
Description
•METHOD AND APPARATUS FOR ESTIMATING CEREBRAL PERFUSION PRESSURE"
Field of the Invention
This invention relates to a method of and/or apparatus for estimating Cerebral Perfusion Pressure (CPP) and, in particular, to a method of and/or apparatus f or estimating CPP non- invasively.
Background
In the treatment of head injured patients, many factors may affect outcome but, in general, outcomes can be predicted by monitoring intracranial pressure (ICP) and arterial blood pressure (ABP). Both systemic hypotension and intracranial hypertension lead to a reduction in CPP (being the difference between ICP and ABP) which, in turn, leads to a consequent potential decrease in cerebral blood flow. Accordingly, the intensive care of head injur ed patients aims to optimise CPP. This, in turn, requires the need to monitor CPP on an ongoing basis.
Direct measurement of both ICP and ABP is complex, often impossible or at best inconvenient, and may prove inaccurate in clinical practice. Fo r example, errors in measuring ICP may arise from temperature drifts of the transducer used or, when using contemporary micro transducers, from uneven distribution of intraparenchymal pressure within the brain. In the case of ABP, arterial pressure at the level of the brain is often underestimated because almost all invasive pressure- monitoring devices obtain readings from peripheral vessels prone to vasospasm and atherosclerosis. Hence, attempts have been made to arrive at a method of estimatin g CPP which, although not capable providing true and accurate readings of CPP, indicate variations in CPP likely to affect outcomes.
It is well documented that varying CPP produces specific changes in cerebral blood flow velocity (FV) which can be measured using transcranial Doppler ultrasonography. By processing the velocity wave forms derived from the Doppler ultrasonography according to particular algorithms, indications of CPP can be obtained.
Previous attempts to measure CPP non-in vasively have concentrated on analysing velocity wave forms derived from the middle cerebral artery feeding one side of the brain only - and often not in real time. Often, because of the siting of the ultrasound probes on the head, the information d erived may be of questionable value. In other cases, such as with global injuries, more useful correlations could be observed if a greater range of data was available from the transcranial Doppler ultrasonography.
It is therefore an object of thi s invention to provide a method of estimating CPP which will provide those treating head injured patients with a greater range of useful data, or which will at least provide a useful choice.
Summary of the Invention
In one aspect the invention pro vides a method of estimating cerebral perfusion pressure (CPP), said method including the steps of:
measuring blood flow velocities in the left and right side middle cerebral arteries; and
assessing CPP from each of said velocities.
Preferably said method further includes calculating the difference in CPP from the individual CPP measures derived from said blood flow velocities.
The blood flow velocities are preferably measured non-invasively and in real time. Doppler ultrasonography is conveniently used.
Whilst the precise method chosen to estimate CPP from blood flow velocity does not form part of the essence of invention, we 5 believe the most accurate estimate is currently obtained by application of the formula:
ABPm*FVd/FVm
where APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
In a second aspect the invention provides a method of deriving, non-invasively, an estimate of cerebral perfusion pressure (CPP) said method including:
calculating individual estimates of CPP from blood flow velocities in the left and right middle cerebral arteries, said velocities being measured using Doppler ultrasonography; and comparing said individual estimates to produce a composite indication of CPP.
In a third aspect the invention provides apparatus for providing an estimate of cerebral perfusion pressure (CPP), said apparatus including detection means for deriving measures o f blood flow velocity in the left and right middle cerebral arteries; and pressure assessment means operable to derive an estimate of cerebral perfusion pressure based on both of said measures of blood flow velocity.
Preferably said detection means is constructed and arranged to derive said blood flow velocities continuously and non-
invasively. To this end, the apparatus preferably further includes transcranial Doppler insonation means operable to insonate sections of the left and right middle cerebral arteries.
Preferably said Doppler insonation means includes a pair of Doppler ultrasound probes mounted on headgear engageable with the head of a patient.
Said assessment means is preferably operable to derive the assessment of CPP by application of the algorithm:
ABPm*FVd/FVm
where APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
Brief Description of the Drawings
One form of the invention will now be described with reference to the accompanying drawings in which:
Figure 1 : shows a diagram of the method used to provide an indication of CPP according to the invention; and
Figure 2: shows a block diagram of the app aratus used to perform the method.
Detailed Description
Referring to Figure 1 , the present invention provides a method of obtaining bilateral estimates of cerebral perfusion pressure (CPP) and, from the two individual estimates, forming a
composite measure of CPP from which considered decisions can be made as to the condition and treatment of the patient under observation.
In the embodiment described herein, true or absolute measures of CPP are not pursued. Rather, non-invasive esti mates are made according to techniques which have been shown to render acceptably accurate measures over a significant sample of patients. These non-invasive estimates are derived by applying an algorithm to wave forms of blood flow velocity produced using transcranial Doppler ultrasonography.
As can be seen, blocks 5 and 6 represent the steps of obtaining a blood flow velocity plot using transcranial Doppler ultrasonography. One form of apparatus used to derive such wave forms is described below but others may be used.
Upon deriving the velocity wave forms, an algorithm is then applied to those from each side of the brain so as to derive individual estimates of CPP, as can be shown by blocks 7 and 8. Standard, software based, curve fo llowing techniques and frequency analysing techniques are used in the application of 20 the algorithm.
The individual estimates of CPP may then be compared, as at 9, to form a composite estimate of CPP.
The algorithm used to produce the individual es timates of CPP from the blood velocity waveforms is not of essence to the invention. Whilst one might use that proposed by Aaslid et al; Springer Verlag Berlin Heildelberg 1986 : 229-231, we prefer to use that proposed by Czosnyka et al at the J D Miller Memorial Meeting held in Edinburgh, October 1996; namely
ABPm*FVd/FVm
6
where: APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
This algorithm, whilst not giving absolute measures of CPP, has been shown to give acceptably accurate results, particularly when detecting CPP < 60mmHg.
Referring now to Figure 2, one form of apparatus suitable for performing the method above described is s hown, in block form, in Figure 2. As can be seen, the apparatus includes a pair of 10 probes 11a, l ib containing crystals configured to transmit and receive ultrasound. The probes may also include pre-amplifiers. We (Deltex Medical Limited) produce suitable 2MHz probes but suitable probes are also available from a number of alternative manufacturers including Scimed, Bristol, United Kingdom.
The probes 11a, l ib are mounted on a headband (not shown) and aligned so as to insonate the left and right middle cerebral arteries.
The probes 11a, l ib are driven by pulsed Doppler transmit and receive circuits 12a, 12b respectively. These are of conventional form.
Signals from each of the circuits 12a, 12b are passed, via an analogue to digital converter, into a dual channel frequency analyser 13 which comprises digital signal processing circuits 14a, 14b to process signals received from the Doppler circuits 12a, 12b respectively, and a system board 15 for calculating individual measures of CPP from both left and right side, and for calculating the difference in CPP between left and right side. The individual measures of CPP are preferably calculated by application of the algorithm:
ABPm*FVd/FVm
Where: APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
Arterial blood pressure can be measured using a manual cuff or an arterial line inserted into, for example, radial or logis pedis arteries. The latter form of apparatus is more invasive but has the advantage of allowing continuous monitoring of APB.
The composite estimate of CPP is derived by calculating the difference between the individual left and right side CPPs.
As the individual and composite estimates of CPP are made by system board 15 they can be displayed, in real time, on the display unit 16.
It will thus be appreciated that the present invention, at least in respect of the preferred form of apparatus de scribed herein, provides a method of and/or apparatus for continuously indicating CPP in real time which gives a wider and more useful range of information to the medical professional.
Claims
8
Claims
1) A method of estimating cerebral perfusion pressu re (CPP ), said method including the steps of:
measuring blood flow velocities in the left and right middle cerebral arteries; and
estimating CPP from each of said velocities.
2) A method as claimed in claim 1 , further including calculating the difference in CPP from the individual CPP estimates derived from said blood flow velocities.
3) A method as claimed in claim 1 or claim 2 wherein the blood flow velocities are estimated non-invasively and in real time.
4) A method as claimed in claim 3 wherein said blood flow velocities are estimated using Doppler ultrasonography.
5) A method as claimed in claim 4 wherein estimates of CPP are obtained from Doppler derived velocity wave forms by application of the algorithm:
ABPm*FVd/FVm
where: APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
9
6) A method of deriving, non-invasively, an estimate of cerebral perfusion pressure (CPP), said method including:
calculating individual indications of CPP from blood flow velocities in the left and right middle cerebral arteries, said velocities being measured using Doppler ultrasonography; and
comparing said individual indications to produce a composite indication of CPP.
7) A method as claimed in claim 6 wherein said indications of CPP are produced continuously and displayed in real time.
8) A method as claimed in claim 6 or claim 7 whe rein said composite indication of CPP is derived by calculating the difference in the individual indications of CPP.
9) Apparatus for providing an estimate of cerebral perfusion pressure (CPP), said apparatus including detection means for deriving estimates of blood flow velocity in the left and right middle cerebral arteries; and pressure assessment means operable to derive a composite estimate of cerebral perfusion pressure based on both of said estimates of blood flow velocity.
10) Apparatus as claimed in claim 9 wherein said detection means is constructed and arranged to derive said blood flow velocities continuously and non-invasively.
11) Apparatus as claimed in claim 9 or claim 10 including transcranial Doppler insonation means operable to insonate sections of the right and left middle cerebral arteries.
10
12) Apparatus as claimed in claim 11 wherein said Doppler insonation means includes a pair of Doppler ultrasound probes mounted on headgear engageable with the head of a patient.
13) Apparatus as claimed in claim 11 or claim 12 wherein said assessment means is operable to derive an estimate of CPP by application of the algorithm:
ABPm*FVd/FVm
where: APBm is the time averaged arterial blood pressure
FVd is the diastolic blood flow velocity; and
FVm is the time averaged blood flow velocity.
14) A method of estimating CPP substantially as hereinbefore described.
15) Apparatus for estimating CPP substantially as hereinbefore described with reference to, and as illustrated in, the accompanying drawings.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0025682A GB2352038B (en) | 1998-05-05 | 1999-04-28 | Method and apparatus for estimating cerebral perfusion pressure |
| AU36210/99A AU3621099A (en) | 1998-05-05 | 1999-04-28 | Method and apparatus for estimating cerebral perfusion pressure |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9809563A GB9809563D0 (en) | 1998-05-05 | 1998-05-05 | Method and apparatus for estimating cerebral perfusion pressure |
| GB9809563.1 | 1998-05-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999056625A1 true WO1999056625A1 (en) | 1999-11-11 |
Family
ID=10831472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1999/001321 Ceased WO1999056625A1 (en) | 1998-05-05 | 1999-04-28 | Method and apparatus for estimating cerebral perfusion pressure |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU3621099A (en) |
| GB (2) | GB9809563D0 (en) |
| WO (1) | WO1999056625A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003012472A1 (en) * | 2001-07-30 | 2003-02-13 | Deltex (Guernsey) Limited | Improvements in or relating to haemodynamic monitors |
| US7547283B2 (en) * | 2000-11-28 | 2009-06-16 | Physiosonics, Inc. | Methods for determining intracranial pressure non-invasively |
| US10617388B2 (en) | 2016-01-05 | 2020-04-14 | Neural Analytics, Inc. | Integrated probe structure |
| US10709417B2 (en) | 2016-01-05 | 2020-07-14 | Neural Analytics, Inc. | Systems and methods for detecting neurological conditions |
| US11090026B2 (en) | 2016-01-05 | 2021-08-17 | Novasignal Corp. | Systems and methods for determining clinical indications |
| US11207054B2 (en) | 2015-06-19 | 2021-12-28 | Novasignal Corp. | Transcranial doppler probe |
-
1998
- 1998-05-05 GB GB9809563A patent/GB9809563D0/en not_active Ceased
-
1999
- 1999-04-28 AU AU36210/99A patent/AU3621099A/en not_active Abandoned
- 1999-04-28 WO PCT/GB1999/001321 patent/WO1999056625A1/en not_active Ceased
- 1999-04-28 GB GB0025682A patent/GB2352038B/en not_active Expired - Fee Related
Non-Patent Citations (5)
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7547283B2 (en) * | 2000-11-28 | 2009-06-16 | Physiosonics, Inc. | Methods for determining intracranial pressure non-invasively |
| WO2003012472A1 (en) * | 2001-07-30 | 2003-02-13 | Deltex (Guernsey) Limited | Improvements in or relating to haemodynamic monitors |
| US11207054B2 (en) | 2015-06-19 | 2021-12-28 | Novasignal Corp. | Transcranial doppler probe |
| US10617388B2 (en) | 2016-01-05 | 2020-04-14 | Neural Analytics, Inc. | Integrated probe structure |
| US10709417B2 (en) | 2016-01-05 | 2020-07-14 | Neural Analytics, Inc. | Systems and methods for detecting neurological conditions |
| US11090026B2 (en) | 2016-01-05 | 2021-08-17 | Novasignal Corp. | Systems and methods for determining clinical indications |
| US11452500B2 (en) | 2016-01-05 | 2022-09-27 | Novasignal Corp. | Integrated probe structure |
| US11589836B2 (en) | 2016-01-05 | 2023-02-28 | Novasignal Corp. | Systems and methods for detecting neurological conditions |
| US12097073B2 (en) | 2016-01-05 | 2024-09-24 | Neurasignal, Inc. | Systems and methods for determining clinical indications |
| US12390191B2 (en) | 2016-01-05 | 2025-08-19 | Neurasignal, Inc. | Integrated probe structure |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0025682D0 (en) | 2000-12-06 |
| GB9809563D0 (en) | 1998-07-01 |
| GB2352038B (en) | 2002-04-24 |
| GB2352038A (en) | 2001-01-17 |
| AU3621099A (en) | 1999-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tsuchiya et al. | Imaging of the basal cerebral arteries and measurement of blood velocity in adults by using transcranial real-time color flow Doppler sonography | |
| US6652466B2 (en) | Blood flow volume measurement method and vital sign monitoring apparatus | |
| CA2585782C (en) | Method and apparatus for non-invasive continuous monitoring of cerebrovascular autoregulation state | |
| EP0898938B1 (en) | Cardiovascular information measurement system | |
| US5505204A (en) | Ultrasonic blood volume flow rate meter | |
| KR100877753B1 (en) | Apparatus and method for measuring hemodynamic parameters | |
| US6626840B2 (en) | Method and system for detecting vascular conditions using an occlusive arm cuff plethysmograph | |
| Maeda et al. | A validation study on the reproducibility of transcranial Doppler velocimetry | |
| US8211031B2 (en) | Non-invasive intracranial monitor | |
| US5715826A (en) | Method and device for assessing the state of blood vessels | |
| US9168023B2 (en) | Method and apparatus for continuously monitoring intracranial pressure | |
| US8043223B2 (en) | Method and apparatus for automated vascular function testing | |
| Ganslandt et al. | Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results | |
| JP2002125941A (en) | Uterine contraction detector and frequency trend apparatus | |
| Fu et al. | A new method for cerebral arterial stiffness by measuring pulse wave velocity using transcranial Doppler | |
| JP4587570B2 (en) | Vascular elastic modulus measuring method, vascular elastic modulus calculating apparatus, and ultrasonic diagnostic apparatus | |
| EP1889571A1 (en) | Ultrasonograph | |
| Huang et al. | The accuracy of ultrasonic estimation of bladder volume: a comparison of portable and stationary equipment | |
| WO1999056625A1 (en) | Method and apparatus for estimating cerebral perfusion pressure | |
| Harrington et al. | Measurement of volume flow with time domain and M‐mode imaging: in vitro and in vivo validation studies. | |
| KR101002079B1 (en) | Blood Vessel Measurement Method | |
| JP2007111245A (en) | Blood circulation state measuring apparatus | |
| EP1250889A1 (en) | Ultrasonic diagnostic device and method of measuring index for indicating vascular status | |
| KR20060078207A (en) | System and method for cardiovascular diagnostic monitoring | |
| JP4880971B2 (en) | Blood circulation measurement device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CU CZ CZ DE DE DK DK EE EE ES FI FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| ENP | Entry into the national phase |
Ref country code: GB Ref document number: 200025682 Kind code of ref document: A Format of ref document f/p: F |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 0025682.6 Country of ref document: GB |
|
| NENP | Non-entry into the national phase |
Ref country code: KR |
|
| 122 | Ep: pct application non-entry in european phase |