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`| | | | | ......... | ......... | ......... | ......... | | ......... | | ......... | ......... | | ......... | | ......... | | ......... | | | ......... | | | | ......... | | | ......... | | ......... | ......... | | | ......... | ......... | | ......... | | | ......... | | ......... | ......... | ......... | | | ......... | ......... | | ......... | | | .........
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`.........
`.........
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`......... .........
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`......... ......... ......... ......... .........
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`c19) United States
`c12) Patent Application Publication
`Mitchnick
`
`c10) Pub. No.: US 2006/0084848 Al
`Apr. 20, 2006
`(43) Pub. Date:
`
`US 20060084848Al
`
`(54) APPARATUS AND METHODS FOR
`MONITORING SUBJE℃TS
`
`(52) U.S. Cl. .................... 600/301; 600/549; 128/903;
`600/595; 600/591; 600/573
`
`(76)
`
`Inventor: Mark Mitchnick, East Hampton, NY
`(US)
`
`(57)
`
`ABSTRA℃I
`
`Correspondence Address:
`Dwight H. Renfrew, Esq.
`Ohlandt, Greeley, Ruggiero & Perle, L.L.P.
`10th Floor
`One Landmark Square
`Stamford，℃ T 06901-2682 (US)
`
`(21) Appl. No.:
`
`10/965,010
`
`(22) Filed:
`
`Oct. 14, 2004
`
`Publication ℃lassification
`
`(51)
`
`Int. Cl.
`A61B 5100
`A61B 51103
`
`(2006.01)
`(2006.01)
`
`This invention provides a device, and method and system for
`its use, for monitoring participants in clinical trials so that
`participant self-reporting, which is known to be notoriously
`inaccurate, can be minimized or eliminat巳d. In preferred
`embodiments, the device is self-contained and self-powered,
`resides on or in a body cavity of the participant, collects data
`monitoring medically relevant aspects of the participant’ s
`behavior and of the local device environment, and stores
`data in a memory on-board the device. An accompanying
`external station reads stored data and prepares it for use.
`Devices may include electrically-active sensors and non(cid:173)
`electrical active sampling sensors. A preferred embodiment
`of the device is in clinical trials of microbicides inhibiting
`transmission of the HIV virus.
`
`\ ‘
`
`SAMSUNG EXHIBIT 1007
`
`Page 1 of 22
`
`

`

`－v呈。因畔KFMWZR呈阳。因－WEE－n呈阳。因
`同｝∞N。。AE。。∞hahap－
`KFMW『－NFN。。。 ∞田园。。畔］｛。吨。
`
`FIG.
`
`/
`
`CONNECTOR)
`
`) 15 (FLEXIBLE
`
`/
`
`CONTACTS)
`17 (EXTERNAL
`
`(ACCELEROMETER)
`
`7
`
`DIAMETER)
`3 (INSIDE
`/,
`
`\
`
`\
`
`\
`
`1 (HOUSING)
`
`(AND "ANTENNA＇”）气9
`OTHER SENSORS
`
`SENSOR)
`
`19 (SAMPLING
`
`PORTS/PORES)
`
`21 (SENS。R
`
`Page 2 of 22
`
`

`

`－v魁畔。EKFMWZ－SE。因－wzeESE。因
`
`KFMW『－NPN。。。
`
`∞田园。。畔N 。吨。
`
`同｝∞N。。AE。。∞hahap－
`
`FIG. 2
`
`一「
`
`MEMORY
`
`35
`
`51
`
`61
`
`APPLICATOR
`
`67’
`
`”'ANTENNA”
`
`57
`
`33
`
`CONTROLLER
`
`MICRO(cid:173)
`
`ACCELER。－
`
`METER
`
`SENSORS
`OPTIONAL
`
`OTHER
`
`THERMISTOR &
`
`SENSOR
`MATERIAL
`PROXIMITY/
`OPTIONAL
`
`49
`
`53
`
`55
`
`POWER CONTROL 45
`
`843
`
`41
`
`INTERFACE/CONTACTS
`
`EXTERNAL
`
`31
`
`Page 3 of 22
`
`

`

`Patent Application Publication Apr. 20, 2006 Sheet 3 of 6
`
`US 2006/0084848 Al
`
`WAITING STATE
`(SLEEP)
`
`71
`
`OPERATIONAL
`STATE (SLEEP)
`
`73
`
`YES
`
`77
`
`ADAPTIVELY
`SAMPLE SENSOR
`DATA
`
`79
`
`STORE DATA IN
`MEMORY
`
`81
`
`SPECIAL STATES
`
`FIG. 3
`
`Page 4 of 22
`
`

`

`Patent Application Publication Apr. 20, 2006 Sheet 4 of 6
`
`US 2006/0084848 Al
`
`101
`
`...
`
`99
`
`105
`
`胃口＝
`
`FIG. 4A
`
`91
`
`READ OUT DATA
`
`93
`
`EXTRACT SENSOR
`DATA
`
`94
`
`CORRECT SENSOR
`DATA
`
`95
`
`REFORMAT
`SENSOR DATA
`
`97
`
`STORE厅RANS MIT
`DATA
`
`FIG. 48
`
`Page 5 of 22
`
`

`

`Patent Application Publication Apr. 20, 2006 Sheet 5 of 6
`
`US 2006/0084848 Al
`
`'
`
`、、
`
`兰、＇
`
`桑拿
`
`等！
`
`FIG. 5A
`
`4品
`
`￥
`
`FIG. 58
`
`Page 6 of 22
`
`

`

`Patent Application Publication Apr. 20, 2006 Sheet 6 of 6
`
`US 2006/0084848 Al
`
`\ ‘
`
`FIG. 5C
`
`Page 7 of 22
`
`

`

`US 2006/0084848 Al
`
`Apr. 20, 2006
`
`APPARATUS AND METHODS FOR MONITORING
`SUBJE℃TS
`
`1. FIELD OF THE INVENTION
`
`[0001] The present invention, in a preferr巳d embodiment,
`relates to monitoring participants in clinical trials of phar(cid:173)
`maceuticals relating to sexual activity, especially those for
`limiting or preventing transmission of sexually transmitted
`diseases (STD时， and provides a device for participant
`monitoring with accompanying systems and methods that
`automatically collects monitoring data with little or no
`participant attention.
`
`2. BACKGROUND OF THE INVENTION
`
`[0002] Women now account for the majority of people
`with human immunodeficiency virus (HIV) infections, and
`young women bear the brunt of new infections in many parts
`of the world. See Copan et al., 2004, Science 304:1911 (and
`the references contained therein). Advances in understand(cid:173)
`ing the molecular mechanisms of HIV sexual transmission
`are focusing new interest and resources on development of
`topical intra-vaginal agents that block HIV infection. Even
`if these agents, known as microbicides, are only partially
`effective at preventing infection, they will hugely comple(cid:173)
`ment existing prevention and treatment methods. Math(cid:173)
`ematical modeling studies estimate that a partially effective
`microbicide used in half of coital acts by 20% of women at
`risk could prevent 2.5 million infections in 3 years.
`
`[0003] Many new microbicides are now under develop(cid:173)
`ment. More than 40 new compounds are being tested in the
`laboratory; many new compounds are in clinical testing; and
`six cand dates are currently in or about to enter phase III
`studies. Further, new microbicide preparations containing
`two or more active ingredients, which are likely to be more
`effective than single active agent preparations, will require
`independent laboratory and clinical testing.
`
`[0004] Yet there are significant and unique obstacles to
`microbicide testing and licensing. Chronic use of topical
`intravaginal drugs to prevent infection is a new concept with
`which regulators have little previous experience. There is no
`surrogate marker or animal model known to reliably predict
`microbicide efficacy in humans. Since microbicides are
`expect巳d to be effi巳ctive only on average, trials require larger
`numbers of participants. All these factors suggest that large
`clinical trials are, if an严hing, even more necessary to
`demonstrate the safety and efficacy of microbicides.
`
`[0005] But the logistics and costs of these studies are
`formidable. Intrinsic characteristics of microbicides require
`that trials have up to tens of thousands of HIV-free, but
`high-risk women participants and that the participants be
`follow巳d for up to several years. During licensing delays
`required by this testing, large numbers of new infections will
`unnecessarily occur if new drugs prove efficacious. Further,
`many trials will necessarily involve participants in devel(cid:173)
`oping countries subject to economic, environmental and
`social stresses. Finally, against this complex background,
`trial data must currently rely essentially on self-reporting of
`sexual habits, which is known to be notoriously inaccurate
`even in the best conditions.
`
`[0006] Thus, it is a worldwide priority to expand capacity
`for rapidly, cheaply, and easily performing efficacy trials of
`
`microbicides and other preventions. Targeted efforts and
`significant financial investment by several organizations
`have established clinical sites capable of conducting these
`microbicide trials according to international guidelines.
`However, these sites are overburdened already with the
`current candidates for phase III trials.
`
`[0007] Therefore, systems and methods that help make
`such trials simpler and more economical are urgently needed
`and will have great benefit. For example, systems and
`methods providing more accurate and up-to-date trial data
`can reduce the number of participants required and shorten
`the time to demonstrate (or not) the efficacy of candidate
`drugs. Such systems and methods are not currently avail(cid:173)
`able.
`
`[0008] A number of references are cited herein, the entire
`disclosures of which are incorporated herein, in their
`entirety, by reference for all purposes. Further, none of these
`references, regardless of how characteriz巳d above, is admit(cid:173)
`ted as prior to the invention of the subject matter claimed
`herein.
`
`3. SU肌f鸟也气RY OF THE INVENTION
`
`[0009] The objects of the present invention are to provide
`unobtrusive devices for automatically monitoring partici(cid:173)
`pants in clinical trials of topical pharmaceutical agents for
`limiting or preventing STD transmission, and also in trials of
`other types of pharmaceutical agents, especially pharmaceu(cid:173)
`tical agents relating to sexual activity. For example, because
`anti-depressants and similar psychoactive agents are known
`to affect patient-reported libido, it may be advantageous to
`objectively monitor patients taking such agents. These
`objects also include providing systems and methods for use
`of such monitoring devices in clinical trials.
`
`[0010] Further objects of the present invention include
`monitoring subjects whether or not engaged in clinical trials.
`Preferred devices reside in a body cavity and can provide
`access to body-core values for, for example, temperature,
`glucose, p02, and the like. Also, the present invention can
`monitor menstrual cycles and their characteristics. Addition(cid:173)
`ally, the present invention can be combined with drug
`delivery devices similarly configured to reside in a body
`cavity, and thereby provide passive or actively-triggered
`drug delivery.
`
`[0011] The inventive principles to be described herein
`provide for monitoring devices that are designed to be
`affixed to, or to reside in a cavity of, a participant in a clinical
`trial (or otherwise the subject of a study) with little or no
`discomfort or risk for extend巳d periods, e.g., weeks, a
`month, or several months, or up to a year or more. These
`devices incorporate sensors and supporting components for
`sensing and recording data relevant to the clinical trial or
`study. This data advantageously includes participant behav(cid:173)
`ioral data that would otherwise require participant self(cid:173)
`reporting or invasive devices. Sensors usually detect the
`local environment where a topical pharmaceutical is to be
`appli巳d, whether or not the topical pharmaceutical has been
`appli巳d, and the like. This data is stored, at least temporarily,
`in the device, and later off loaded and processed to provide
`useful participant monitoring data. The preferred practical
`application of these principles, and the preferred but not
`limiting embodiments of the device, is as an intra-vaginal
`device used during trials of pharmaceuticals, especially
`
`Page 8 of 22
`
`

`

`US 2006/0084848 Al
`
`Apr. 20, 2006
`
`2
`
`microbicides, for preventing or limiting STD (e.g., HIV)
`transmission. The following description is directed and
`exemplified largely in terms of these preferred but non(cid:173)
`limiting embodiments.
`
`[0012] Accordingly, a preferred intra-vaginal device of
`this invention includes sensors for, at least, det巳:cting and
`storing the occurrences of sexual activity (primarily, inter(cid:173)
`course). Sexual activity is preferably detected by observing
`characteristic patterns of participant motion as sensed by an
`acceleration. Preferably, devices also include sensors for
`other aspects of the vaginal environment and for detecting
`the application or presence of topical pharmaceuticals. Addi(cid:173)
`tional sensors that can be part of a device include tempera(cid:173)
`ture sensors, pH sensors, heart rate sensors, p02 sensors
`(based on pulse oximeter electror让cs), and the like. If
`available, sensors for specific chemicals can be included,
`such as sensors for selected pharmaceuticals, microbicides,
`spermicides, and the like. Further, chemical or physical
`labels can be added to pharmaceuticals, pharmaceutical
`applicators, and the like, to simplify their detection. One
`preferred physical label is magnetic micro-beads or other
`magnetic materials in combination with a compact magnetic
`自己ld sensor in a device.
`
`[0013] A preferred device also includes supporting com(cid:173)
`ponents for making use of these electrically-active types of
`sensors. Preferably, a device includes a micro-controller
`(MC), or the equivale凶， for retrie飞ring data 企om sensors, for
`storing retrieved data in an on-board memory, and for
`controlling overall device operation, especially by managing
`power use for longer battery life. A device 臼rther advanta(cid:173)
`geously includes data memory, power management cir(cid:173)
`cuitry, and other components known in the art. Data com(cid:173)
`pression is preferably used to conserve memory. All
`components are selected to have compact form factors and
`low and/or controllable power consumption.
`
`In one preferred embodiment, these sensors and
`[0014]
`supporting components are packaged into a single unit sized
`and shaped for residing intra-vaginally in a monitored
`participant. It is paramount that a device be safe, convenient,
`comfortable, and acceptable to participants, and that it
`interfere only minimally, or not at all, with the participants
`normal sexual activities. A preferred configuration is ring(cid:173)
`shaped and sized to reliably reside in the back of the vagina
`adjacent to the cervix much like a diaphragm or cervical cap.
`Ring-shaped intra-vaginal devices have been used for drug
`delivery and other applications, and patients have found
`them comfortable and acceptable. S巳毡， for example, U.S.
`Pat. No. 4,827,946, U.S. Pat. No. 5,928,195, and Rathbone
`et al. eds., 2003, Modified-Release Drug Delivery T巳chnol­
`ogy, C.H.I.P.S., Weimar, Tex. (all presenting further details
`of intra-vaginal ring technology; and all incorporated by
`reference herein in their entireties for all purposes). Alter(cid:173)
`nate physical con且gurations, such a cylindrical shape, are
`also within the scope of this invention. Devices are prefer(cid:173)
`ably constructed from m巳dical-grade silicone elastomers, as
`these materials have already been proven suitable in intra(cid:173)
`vaginal drug-delivery rings.
`
`In other preferred embodim已由， the device may be
`[0015]
`configured into 阳o (or more) separate units. In one such
`configuration, the device includes an intra-vaginal unit and
`a cooperating extra-vaginal unit, the extra-vaginal unit being
`on or near the participant, for example, being supported on
`
`the participant’ s clothing. These two units communicate
`wirelessly using one of the available very low power, short
`range radio link protocols (e.g., Bluetooth) now available as
`single chip integrated circuit (IC) transceivers. For example,
`the intra-vaginal unit can retrieve sensor data and transmit it
`to the extra-vaginal unit; the extra-vaginal unit can r巳：ceive
`and store sensor data and perform overall management of
`both units. The intra-vaginal can then use simpler, smaller,
`and more power efficient supporting components, while the
`larger components requiring more power, such as the MC,
`may reside externally where the physical constraints are less.
`Alternatively, the extra-vaginal unit may be supplemented or
`replaced by an external station to which data is be trans(cid:173)
`mitted from time-to-time to free memory in the intra-vaginal
`unit. In a further alternative, the two units may include an
`inductive coupling (e.g., forming a transformer) so that the
`extra-vaginal unit can recharge from time-to-time batteries
`in the intra-vaginal unit. It is then possible, for ex缸口ple, that
`the intra-vaginal unit be even more compact by dispensing
`with batteries and power control. The extra-vaginal unit then
`provides power to the intra-vaginal unit only when n臼ded
`to retrieve and transmit sensor data; otherwise, the intra(cid:173)
`vaginal unit is inactive. Finally, in other embodiments, the
`intra-vaginal unit may be entirely dispens巳d with, and all
`data sensed from an external unit on or near the participant.
`
`In the following, without limitation, the de叽ce of
`[0016]
`this invention is described largely in its single-unit embodi(cid:173)
`ment. Constructing an embodiment with two (or more) units
`simply requires, first, that the functions and components of
`the single unit be distribut巳d 缸nong the two units, and
`second, that a wireless link component and/or optional
`inductive coupling by added to both units. Wireless links and
`inductive coupling are already known and used in the art.
`Therefore, in view of the following description of the
`single-unit embodiments, it will be readily apparent to one
`of ordinary skill in the art how other embodiments can be
`constructed.
`
`[0017] Finally, this invention includes also systems and
`methods for making device monitoring data available for its
`ultimate uses. Data is retrieved or read-out from the single
`unit device usually when the device is removed from the
`participant. Preferably, electrical contact pads provided on
`the device interface to an external data reader so that data
`can non-destructively be moved from the on-board memory
`to an external station or system, such as a standard personal
`computer (PC). (In multi-unit embodiments, data can be
`wirelessly retrieved from time-to-time without device
`removal.) The external station performs basic processi吨，
`such as extracting data from the format in which it was
`stored in device on-board memory and correcting apparent
`sensor errors (such as baseline drift). After such processing,
`the data is transmitted or sent for its ultimate uses.
`
`[0018] A device can also advantageously include electri(cid:173)
`cally-non-active sensors. Preferred el巳：ctrically-non-active
`sensors include passive physical sensors designed to S缸口ple
`and retain components encountered in the device’ s (intra(cid:173)
`vaginal) environment. Components sampled by such a sen(cid:173)
`sor are detected upon device removal using known chemical
`and biological techniques that are usually destructive of the
`sensor. A preferred embodiment of a sampling sensor
`includes an absorbent material disposed in an enclosed
`cavity in the device, the cavity communicating with the
`external device environment through pores and/or a mem-
`
`Page 9 of 22
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`

`

`US 2006/0084848 Al
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`Apr. 20, 2006
`
`3
`
`brane. Characteristics of the membrane and/or absorbent
`material can be selected to give such a sampling sensor a
`degree of selectivity and specificity. For example, correctly
`sized membrane pore can exclude external components
`larger that desired; or surface treatment of membrane pores
`can favor the passage of desired classes of external compo(cid:173)
`nents. The absorbent material can be selected to preferen(cid:173)
`tially retain desired external components, such as com(cid:173)
`pounds, biologicals, or biological agents, by being
`hydrophobic, or hydrophilic, or positively charged, or nega(cid:173)
`tively charg巳：d, or neutral, or the like. Further, the absorbent
`material can be selected to selectively bind and retain
`selected external components. For example, this material
`can have bound antibodies specific for viruses, such as
`hepatitis C, HPV, HIV, and the like, and other biological
`agents. In another example a sensor specific for PSA (pros(cid:173)
`tate specific antigen) can be present. PSA, being only
`present in males, would be indicative of unprotected inter-
`course.
`
`In a first embodiment, this invention includes an
`[0019]
`apparatus for monitoring a subject which comprises a hous(cid:173)
`ing adapted to reside in an anatomic cavity of the subject's
`body, the housing having no external physical connection,
`and at least one sensor of acceleration within the housing.
`
`[0020] Aspects of the first embodiment further include:
`that the anatomic cavity normally opens externally; that the
`housing is further adapted to permit insertion and removal
`by the subject; that the anatomic cavity is a vagina; that the
`housing is ring-shap巳d; that at least one sensor is selected
`from the group consisting of a sensor of pH, a sensor of
`temperature, a sensor of the occurrence of menstruation, a
`sensor of the proximity of magnetic materials, a sensor of
`the proximity of a target object.
`
`[0021] Additional aspects of the first embodiment include:
`a computer-readable memory within the housing, and a
`controller within the housing that retrieves measurements
`from at least one sensor and stores the retrieved measure(cid:173)
`ments in the memory; or an external ur山， and an RF
`transmitter within the housing that transmits sensor mea(cid:173)
`surements to the external unit; or a s缸口pling sensor that
`samples components present in the external environment of
`the apparatus that comprises an absorbent material disposed
`in a cavity in the housing, and one or more pores through
`which components of the external environment have access
`to the absorbent material, wherein components are sampled
`by being absorbed by the absorbent material a武er passing
`though the pores from the external environment; or a bio(cid:173)
`sensor for sensing biological components that is disposed in
`the housing and having access to biological components
`present in the external environment.
`
`[0022] Additional aspects of the first embodiment include:
`that the biosensor comprises antibodies selective for one or
`more biological components; that the antibodies are selec(cid:173)
`tive for one or more sexually transmitted disease agents; that
`sexually transmitted disease agents comprise the human
`immunodeficiency virus (HIV).
`
`In a second embodiment, this invention includes an
`[0023]
`apparatus for monitoring a female subject that comprises a
`housing adapted to reside in the subject’ s vagina, the hous(cid:173)
`ing having no external physical connection, and one or more
`sensors within the housing comprising at least one sensor
`selected from the group consisting of a sensor of accelera-
`
`ti on, a sensor of pH, a sensor of temperature, a sensor of the
`occurrence of menstruation, a sensor of the proximity of
`magnetic materials, and a sensor of the proximity of a target
`object.
`
`[0024] Aspects of the second embodiment further include:
`that peak values of the measured acceleration and the
`occurrence times of the measured peak values are deter(cid:173)
`mined; that the subject is determined as likely to be engaging
`in sexual activity, or as not likely to be engaging in sexual
`activity, by comparing characteristics of the acceleration
`peak values and of the peak-value occurrence times with
`characteristics expected ifthe subject is actually engaging in
`a sexual activity.
`
`In a third embodiment, this invention includes an
`[0025]
`apparatus for monitoring a subject that comprises a housing
`adapted to reside in an anatomic cavity of the subject’ s body,
`the housing having no external physical conn巳：ction, and at
`least one sensor of the proximity of magnetic materials
`within the housing. The third embodiment is advantageously
`used with a pharmaceutical preparation applied in the prox(cid:173)
`imity of the apparatus that includes magnetic materials.
`
`In a fourth embodiment, this invention includes an
`[0026]
`apparatus for monitoring a subject that comprises a housing
`adapted to reside in an anatomic cavity of the subject’ s body,
`the housing having no external physical conn巳：ction, and at
`least one sensor of the proximity ofa target object within the
`housing. Aspects of the fourth embodiment further include:
`that the proximity sensor generates an electromagnetic 自己ld
`and senses perturbations in the electromagnetic 自己ld, and
`wherein the target object perturbs an electromagnetic 自己ld
`and is thereby detected; that the target object comprises a
`conductive element and/or an inductive element that per(cid:173)
`turbs an electromagnetic 自己ld; that the target object com(cid:173)
`prises an applicator for a pharmaceutical; that the target
`object comprises a contraceptive device; or that the contra(cid:173)
`ceptive device comprises a condom.
`
`In a 且武h embodim巳n
`[0027]
`appara阳s for monitoring a subject that compris巳s a housing
`adapt巳d to reside in an anatomic cavity of th巳 subj 巳ct’s body,
`the housing having no external physical connection, and a
`S缸口pling sensor for s缸口pling components of the external
`environment of the apparatus, the sampling sensor compris(cid:173)
`ing an absorbent material disposed in a cavity in the housing,
`and one or more pores through which components of the
`external environment have access to the absorbent material,
`wherein components are sampled by being absorbed by the
`absorbent material after passing though the pores from the
`external environment.
`
`In a sixth embodiment, this invention includes an
`[0028]
`apparatus for monitoring a female subject’ s sexual activity
`that comprises a housing adapted to reside in the subject’ s
`vagina, the housing having no external physical connection,
`one or more sensors within the housing, a computer-readable
`memory within the housing, a controller within the housing,
`and a program for awakening periodically from a low power
`sleep state in order to determine from sensor measurements
`whether or not the subject is likely to be engaging in sexual
`activity, retrieving measurements from at least one sensor
`and storing the retriev巳d measurements in the memory
`during a period in which the subject is determined as likely
`to be engaging in sexual activity, and switching back to the
`low power sleep state if the subject is determined as not
`
`Page 10 of 22
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`

`US 2006/0084848 Al
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`Apr. 20, 2006
`
`4
`
`likely to be engaging in sexual activity. An aspect of the
`sixth embodiment includes that acceleration measurements
`are adaptively retrieved and stored so that the acceleration is
`more frequently sampled near the expected times of an
`acceleration peak value, and is less frequently sampled
`between the expected times of acceleration peak values.
`[0029]
`In a seventh embodim巳盹 this i盯ention includes
`an apparatus for monitoring and drug delivery that com(cid:173)
`prises a housing adapted to reside in an anatomic cavity of
`the subject’ s body, the housing having no external physical
`connection; the housing comprising an embedded pharma(cid:173)
`ceutical agent that diffuses from the housing into the ana(cid:173)
`tomic cavity, and one or more sensors within the housing.
`Aspects of the seventh embodiment further include: that the
`pharmaceutical agent is embedded throughout the housing
`material; or that the pharmaceutical agent is embedded in a
`core of the housing.
`[0030]
`In an eighth embodiment, this invention includes
`an apparatus for subject monitoring and drug delivery that
`comprises a housing adapted to reside in an anatomic cavity
`of the subject’ s body, the housing having no external physi(cid:173)
`cal connection, a reservoir of a pharmaceutical agent within
`the housing, and one or more sensors within the housing, a
`controller within the housing, and a program for retrieving
`measurements from at least one sensor and determining
`whether or not a condition is satisfied in dependence on the
`retriev巳d measurements, and if the condition is determined
`to be satisfi巳d, signaling that an amount of the pharmaceu(cid:173)
`tical agent is to be released in the anatomic cavity. An aspect
`of the ei悼th embodiment further includes that the condition
`to be satisfied comprises whether the subject is likely to be
`engaging in a sexual activity.
`[0031]
`In a m由 embodiment, this i盯ention i时ludes a
`computer readable memory with a progr缸丑 for performing
`the methods of this invention. An aspect of the ninth
`embodiment further comprises that the method comprises
`awakening periodically from a low power sleep state in
`order to determine from acceleration measurements whether
`or not the subj 巳：ct is likely to be engaging in sexual activity,
`retrieving measurements from at least one sensor and storing
`the retrieved measurements in the memory during a period
`in which the subject is determin巳d as likely to be engaging
`in sexual activity, and switching back to the low power sleep
`state ifthe subject is determined as not likely to be engaging
`in sexual activity.
`In a tenth embodiment, this invention includes a
`[0032]
`system 企om monitoring female subjects that comprises a
`monitoring apparatus comprising a housing adapted to
`reside in the subject’ s vagina, the housing having no external
`physical connection, and one or more sensors within the
`housing comprising at least one sensor selected from the
`group consisting of a sensor of acceleration, a sensor of pH,
`a sensor of temperature, a sensor of the occurrence of
`menstruation, a sensor of the proximity of magnetic mate(cid:173)
`rials, and a sensor of the proximity of a target object, a
`computer-readable memory within the housing, and a con(cid:173)
`troller within the housing that retrieves measurements from
`at least one sensor and stores the retrieved measurements in
`the memory, and a computer for reading measurements
`stored in the memory of the monitoring apparatus during a
`prior period of residence in the subject.
`In an eleventh embodiment, this invention includes
`[0033]
`a method of conducting clinical trials using a plurality of
`
`subjects that comprises providing to at least one subject a
`monitoring apparatus comprising a housing adapted to
`reside in the subject’ s vagina, the housing having no external
`physical connection, and one or more sensors within the
`housing comprising at least one sensor selected from the
`group consisting of a sensor of acceleration, a sensor of pH,
`a sensor of temperature, a sensor of the occurrence of
`menstruation, a sensor of the proximity of magnetic mate(cid:173)
`rials, and a sensor of the proximity of a target object, a
`computer-readable memory within the housing, and a con(cid:173)
`troller within the housing that retrieves measurements from
`at least one sensor and stores the retrieved measurements in
`the memory, reading measurements stored in the memory of
`the monitoring apparatus a武er a period of subject use, and
`transmitting the measurements read for analysis.
`
`[0034]
`In a twelfth embodiment, this invention includes a
`pharmaceutical preparation that comprises one or more
`pharmaceutical agents; and embedded magnetic materials
`sufficient to permit a sensor for magnetic materials to sense
`the proximity of the pharmaceutical preparation.
`
`invention
`this
`thirteenth embodiment,
`In an
`[0035]
`includes an apparatus for monitoring a female subject’ s
`sexual activity that comprises a housing adapted to reside in
`the subject's vagina, the housing having no external physical
`connection, one or more sensors including at least one
`sensor of acceleration within the housing, a controller within
`the housing that determines whether or not the subject is
`likely to be engaging in sexual activity, or is not likely to be
`engaging in sexual activity, by comparing characteristics of
`the acceleration signals with characteristics expected if the
`subject is actually engaging in a sexual activity.
`
`[0036] Further this invention includes combinations and
`subcombinations of the various embodiments, and aspects
`described herein.
`
`4. BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0037] The present invention may be understood more
`fully by reference to the following detail巳d description of
`preferred embodiments of the present invention, illustrative
`examples of specific embodim巳nts of the invention, and the
`appended figures in which:
`
`[0038] FIG. 1 illustrates an exer叩lary of the device;
`
`[0039] FIG. 2 illustrates a block diagram of the device;
`
`[0040] FIG. 3 illustrates on-line device processing;
`
`[0041] FIGS. 4A-B illustrate off-
`data; and
`
`[0042] FIGS. SA-C illustrate an example of an embodi(cid:173)
`ment of this invention.
`
`5. DETAILED DESCRIPTION OF THE
`PREFERRED E肌1BODI肌1ENTS
`
`[0043] The preferred embodiments of this invention are
`single-ur山， intra-vaginal monitoring devices that include
`sensors for detecting sexual activity, and optionally, also for
`detecting/sampling other aspects of the intra-vaginal envi(cid:173)
`ronment. This invention also includes multi-unit embodi(cid:173)
`ments, and further embodiments for residing elsewhere in or
`on the body and detecting other parameters of medical/
`
`Page 11 of 22
`
`

`

`US 2006/0084848 Al
`
`Apr. 20, 2006
`
`5
`
`clinical interest. Headings are used here, and throughout tl山
`application, for clarity and convenience only.
`
`Device Configuration and Components
`
`[0044] With reference to FIG. 1, device housi吨 1, which
`encloses the device’ s sensors and supporting components, is
`shaped and sized for safety and subject acceptability, pro(cid:173)
`viding, for example, comfort, ease of insertion and removal,
`convenience, and little or no interference with a participant’ s
`(w四rer's) sexual activities. A ring shape (torus) with a
`generally circular to oval cross section to be worn or reside
`at the t