CN101850153A - Disposable drug administration device with own power - Google Patents
Disposable drug administration device with own power Download PDFInfo
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- CN101850153A CN101850153A CN200910048805A CN200910048805A CN101850153A CN 101850153 A CN101850153 A CN 101850153A CN 200910048805 A CN200910048805 A CN 200910048805A CN 200910048805 A CN200910048805 A CN 200910048805A CN 101850153 A CN101850153 A CN 101850153A
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- storage chamber
- micropin
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Abstract
The invention relates to a disposable patch-type drug administration device with own power, which comprises a microneedle, a drug storage chamber, a pressure chamber, an activation device and a piston, wherein the drug storage chamber contains a drug for infusion, and a liquid channel is arranged between the drug storage chamber and the microneedle; a pressure device in the pressure chamber hydraulically or directly acts on the drug storage chamber, and the activation device is used for starting a pressure exerting device in the pressure chamber; and the piston is usually positioned in the drug storage chamber, unidirectionally moves as the pressure increases, and separates the drug liquid in the pressure chamber from the drug liquid in the drug storage chamber. The invention simultaneously relates to a shell of the drug administration device and a use method thereof.
Description
Technical field
The present invention relates to a kind of doser and using method thereof.Particularly, this device is for disposable use and have the doser of self power.This device can effectively be controlled medicine-feeding rate, prolongs administration time.
Background technology
Drug administration by injection is the most reliable a kind of route of administration, for a lot of macromolecular drugs, and the route of administration that drug administration by injection is normally unique.Yet drug administration by injection is faced with needs of patients professional training, patient's feared state of mind, safety, a series of problems such as cross infection, and therefore, changing route of administration is a research field that is subjected to extensive concern.
Micropin is a kind of transdermal machinery, and it can only penetrate horny layer and form administration channel, does not stimulate subcutaneous pain nerve [1-2] simultaneously.Micropin injection or micropin fusion are a kind of Wicresoft route of administration, for the subcutaneous injection administration provides a kind of attractive mode of sending.Chang Gui subcutaneous injection administration relatively, micropin is injected that common drug effect equates even is higher sometimes, can overcome the problem that most of drug administration by injection faces simultaneously, for example, its Wicresoft's effect can directly solve patient's compliance issues, and the micropin micropin has higher safety.
McAllister etc. utilize the long glass empty micropin of 900um to there not being hair rat input insulin [3].Experimental result has shown the effect that blood glucose descends insulin dose is relied on, under the 10psi infusion pressure, and rat insulin injection solution 30 minutes, blood sugar level is stable to descend; Under the 14psi infusion pressure, rat blood sugar was lower than basic value 70% in sustainable 5 hours.
Davis etc. also are used for empty micropin array not having hair diabetes rat experiment [4].Insulin enters in the rat body by the long 4x4 metal hollow pin array of 500 μ m, and administration is glucose level decline 47% in the rat body after 4 hours, observes the corresponding rising of insulin level in the experimental animals simultaneously.
Empty micropin itself is less, and it is limited to thrust skin depth, belongs to intradermal administration on the stricti jurise.For a lot of vaccine kinds, intradermal administration can improve immunological effect, reduces antigen dose [5-6], and therefore, micropin provides a kind of attractive vaccine delivery mode.
Although carry the theory of medicine just to propose [U.S. Patent number 3,964,482] as far back as the seventies in 20th century by micropin, the technology barriers of micropin administration are still its large-scale production and the commercial major obstacle of using.For example, the micropin administration faces usually because the micropin volume is small and the skin shallow-layer thrusts the leakage that causes, and simultaneously, microneedle devices causes the skin histology extruding, further increases the resistance of liquid input of knowing clearly, thereby has reduced medicine-feeding rate [7].
For example, Davis etc. studies have shown that the micropin of 1080 μ m length only can enter skin surface 100-300 μ m, and this moment, maximum input rate was 15 μ L/hr, and by this rate calculations, the medication amount that input can reach drug effect needs some hrs.Therefore, effectively micropin drug administration by injection system should be able to provide slowly, the stable administration that reaches the long period.
Roxhed etc. attempt adopting the motive force [8] of thermal expansion bead as the micropin drug-supplying system, observe this device prototype insulin administration speed at 2-4 μ L/hr.The medicine-feeding rate of this device is determined by the quantity and the external energy of bead.It should be noted that the author observes, when medicine-feeding rate reaches 60 μ L/hr the dyestuff leakage can take place, this conforms to the result of study of Davis.Restricted except medicine-feeding rate, therefore this device need limit the size and the ease of use of device by outside energy.
At above problem, people such as Good have reported a kind of portable water activation Micropump, and microsphere substrate [9] hydrophilic material of volumetric expansion or expansion bead were as administration power after its principle was based on and absorbs water.The expansion rate of this material makes us surprised, and its expansion rate of the gel of some porous surface can reach 1: 1000.The defective of this medication is that the volumetric expansion speed of material is too fast, is difficult to regulate.According to the report of Good, the volumetric expansion of this material can be finished at chance water several seconds, and its speed can be up to 17 μ L/min/mg.This is useful for micro-fluidic system, but is not suitable for the micropin injecting systems of slow administration.
People such as Good have also reported the example [10] of another kind of Micropump according to the effervescent generated reactive gas.This reaction is to adopt some common reagent such as carbonate or bicarbonate and acid to react, and the carbon dioxide of release can generation pressure in airtight system.Experimental results show that reaction rate can reduce when using less sour of oarse-grained solid reactant or dissolubility.Even these parameters are all fixed, medicine-feeding rate is still in a few minutes and just can finishes, and is still too fast for micropin administration model.
Except that the above-mentioned machinery of mentioning, spring, retractable material or atmospheric pressure are also usually as administration power.For example, United States Patent (USP) 7,481, a kind of miniflow doser of mentioning in 337, thus its principle is to utilize constant force spring as the at the uniform velocity administration of administration power, and device volume is minimized.In addition, introduced the device of a kind of Bellivelle of employing type spring in the U.S. Patent application book 2008/0215015 as administration power.
Related to the device of multiple administration power design in the following patent, having comprised: United States Patent(USP) Nos. 4,692,151,4,734,092,4,741,733,4,753,651,4,769,008,4,772,263,4,781,688,4,886,499,4,902,278,4,968,301,5,045,064,5,318,557,5,398,851,5,957,895,6,656,147,6,669,668,7,115,108,7,220,244,7,250,037,7,270,648,7,410,476,7,481,337,7,470,253; U.S. Patent application book Nos.20030109827,20030135259,20080319385,20080033359.
With micro pump and micropin combination is a good medication.Reported in a lot of patents or the application for patent and adopted manual compressing, spring or alternate manner to come administration, these patents comprise: United States Patent (USP) 3964482,52500: 23,5957895,6503231,6656147,6743211,6780171,6623457,6960193,6939324,7047070,6808506,7083592,7115108,7156838,7250037,7410476,7429258; US patent application 20080215015; PCT patent WO03/022330, WO02/002179, WO03/024507, WO04/033021, WO06/054280, WO06/132602; Chinese patent CN02812823.0; And european patent application book EP1925333.
All patents and non-patent reference mentioned among the present invention are all mentioned in citing document.
The character of micropin drug-supplying system is can be slowly and the administration of continuous and effective.In some applications, its medicine-feeding rate is normally with dozens of minutes, several hours even meter over these days, and the portable device that those have been in the news can not reach the administration time of length like this.
Existing many drug-supplying systems still exist defective, and therefore a kind of Wicresoft, self-powered, cheap, simple and flexible need be provided, be easy to operate and control, and the device of sustainable administration.
Summary of the invention
This invention may be summarized to be the doser of a kind of Wicresoft, disposable use, self-powered patch form.Device comprises micropin; And the drug storage chamber that fluid path is arranged between the micropin wherein contains the medicine that is useful on infusion; With the spring is the pressure chamber of power, and as administration power, constant force spring links to each other with drug storage chamber by piston; Activator appliance in the pressure chamber is provided with the first and second two positions, when activator appliance when primary importance moves to the second position, administration begins; A piston also is housed in the drug storage chamber, and piston can unidirectionally move when spring is exerted pressure, and the medicine and the external world are separated.In some implementations, this device is disposable.
This invention provides a kind of medication for objective body simultaneously, comprises concrete dosing step: will install on the skin that directly sticks to objective body; Start activator appliance, constant force spring begins to exert pressure; To install to stick for a long time and on objective body skin, in medicine enters body, produce drug effect.Its medicine-feeding rate depends primarily on the speed-limiting device in administration channel or the hydraulic pressure transfer medium.
Simultaneously, the present invention specifically comprises doser, medicine for objective body provides a medicine box; and other compositions, for example operation instructions prevent the protector that micropin damages; the partition apparatus that stops reaction to start adheres to adhered layer on the skin with device, with and/or use after the processing bag.In some implementations, the doser in the medicine box may be disposable.
Concrete summary of the invention is as follows:
A kind of doser of giving the objective body medication is characterized in that this device comprises:
A) micropin;
B) be closed in one or more drug storage chambers in the device, fluid path arranged between drug storage chamber and the micropin and contain the medicine of being sent;
C) be closed in pressure apparatus in the device, pressure apparatus or and drug storage chamber between fluid path is arranged or directly acts on piston in the drug storage chamber;
D) be used for the active device of starting pressure device, active device is designed to the primary importance and the second position, has an active device to cut off between the primary importance and the second position; When active device when primary importance moves to the second position, pressure apparatus is activated;
E) be positioned at the piston of drug storage chamber, piston is unidirectional to be moved along with pressure increases;
F) comprise a removable protector that invests the device outside, in order to prevent the micropin injury;
G) comprise an adhered layer that is positioned at bottom of device, be used to stick in the objective body skin surface;
H) pressure apparatus that is closed in the device is a constant force spring.
Drug storage chamber among the present invention is cylindric;
Drug storage chamber height among the present invention and internal diameter ratio are between 2: 1 to 1000: 1;
Between drug storage chamber among the present invention and the pressure chamber jointing is arranged;
Drug storage chamber among the present invention comprises one and be used for pouring into the inlet that needs the infusion medicinal liquid in drug storage chamber;
Active device among the present invention is to do the combination of selecting one or more devices the valving of power and the heater from pushing pin device, wrench device, pull unit, battery.
Active device among the present invention comprises an active device and cuts off, and is used to guarantee that active device remains on primary importance, prevents that active device from moving to the second position by primary importance.
Comprise a flow restrictor among the present invention between drug storage chamber piston and the pressure apparatus.
Doser comprises a watch window among the present invention, is used for monitoring the situation of movement of piston at drug storage chamber.
A kind of doser of giving the objective body medication comprises to patient's two administrations of two kinds of medicines of infusion simultaneously divide device at least, comprising:
A) first and second micropin;
B) first administration divides the drug storage chamber of device inside, between first drug storage chamber and first micropin fluid passage is arranged, and contains the first kind of medicine that is useful on infusion;
C) second administration divides the drug storage chamber of device inside, between second drug storage chamber and second micropin fluid passage arranged, and contains the second kind of medicine that is useful on infusion;
D) be closed in first administration and divide first pressure apparatus in first pressure chamber in the device, first pressure apparatus or and fluid reservoir between fluid path is arranged or directly acts on piston in the fluid reservoir;
E) be closed in second administration and divide second pressure apparatus in second pressure chamber in the device, second pressure apparatus or and fluid reservoir between fluid path is arranged or directly acts on piston in the fluid reservoir;
F) active device is used for starting first pressure apparatus in first pressure chamber and second pressure apparatus in second pressure chamber; Active device has the primary importance and the second position, has an active device to cut off between the primary importance and the second position; When primary importance moved to the second position, the pressure apparatus in first pressure chamber and second pressure chamber was activated with active device;
G) first drug storage chamber and second drug storage chamber have a piston respectively, piston is under the pressure effect of first pressure chamber and the increase of second pressure chamber, unidirectional respectively moving completely cuts off the medicine in the medicine in first fluid reservoir and second drug storage chamber and first pressure chamber and second pressure chamber.
H) comprise a removable protector that invests the device outside, in order to prevent the micropin injury;
I) comprise an adhered layer that is positioned at bottom of device, be used to stick in the objective body skin surface;
J) pressure apparatus that is closed in the device is a constant force spring.
Second kind of medicine in first kind of medicine in first drug storage chamber among the present invention and second drug storage chamber is identical or different.
First kind of pressure apparatus and second kind of pressure apparatus among the present invention are identical or different.
Doser of the present invention is disposable use.
The using method that among the present invention is the doser of a kind of medicine of patient's infusion comprises:
A) device is sticked on the objective body skin surface;
B) by active device is moved to the second position from primary importance, the starting pressure device, simultaneously
C) assurance device is pasted on the objective body skin surface all the time, in treatment effective dose of medicine thing input objective body body.
The using method that among the present invention is the doser of at least two kinds of medicines of patient's while infusion comprises:
A) device is sticked on the objective body skin surface;
B), start first pressure apparatus in first pressure chamber and second pressure apparatus in second pressure chamber by active device is moved to the second position from primary importance;
C) assurance device is pasted on the objective body skin surface all the time, in two kinds of medicine input objective body bodies of treatment effective dose.
The using method of doser comprises device is sticked on before the objective body skin surface among the present invention, removes protector.
Among the present invention the using method of doser further comprise active device moved to the second position from primary importance before, remove active device and cut off.
Selectable infusion of drug approach in the doser using method of the present invention comprises: Intradermal infusion, h inf, intramuscular infusion and venoclysis.
There is medicine box doser outside among the present invention.
Comprise a stand-by protection in the doser medicine box among the present invention and paste, be used to prevent unexpected micropin injury.
Comprise a standby active device in the doser medicine box among the present invention and cut off, be used to prevent that doser from being activated by accident.
Comprise a standby adhered layer in the doser medicine box among the present invention, be used for doser is pasted on the objective body skin surface.
Description of drawings
Fig. 1 is that the present invention is to push the external structure sketch map of bolt as doser 100 designs of active device.Figure 1A is shown as this device unused state, and Figure 1B is shown as this device and removes protector and active device partition, and Fig. 1 C is shown as this device and is in state of activation.
Fig. 2 is the bottom view of device administration 100.Fig. 2 A is shown as this device and does not remove protector, and Fig. 2 B is shown as this device and removes protector.
Fig. 3 is the decomposition chart of doser 100.
Fig. 4 is the component drawings of internal structure in the doser 100.
Number in the figure is represented: 100-is to push the doser of bolt as active device, 101-bottom, 102-top; the 103-drug storage chamber, 104-front connector, joint behind the 105-; 106-base charge hole, the 107-piston, 108-pushes bolt; the 109-push rod, 110-constant force spring, 111-protector; 112-cuts off, and 113-pushes at the top bolt perforate, the 114-micropin; the 115-flow restrictor, 116-spring fixed bar, 117-spring pressure sheet; the 118-interlocking gear; 119-bottom micropin access hole, 120-spring pressure sheet bayonet socket, 121-perfusion mouth rubber blanket; the 122-charging door; 123-pushes the bolt card article, the shellproof blocking-up of 124-, 125-watch window.
Fig. 5 is the external structure sketch map that comprises the doser 200 of Hydraulic Power Transmission System provided by the invention.Fig. 5 A is shown as device 200 and is in unactivated state, and Fig. 5 B is shown as this device and removes protector and active device partition, and Fig. 5 C is shown as this device and is in state of activation.
Fig. 6 is the bottom view of doser 200.Fig. 6 A is shown as this device and does not remove protector, and Fig. 6 B is shown as this device and removes protector.
Fig. 7 is the decomposition chart of doser 200.
Fig. 8 is the component drawings of doser 200 internal structures.
Number in the figure is represented: 200-comprises the doser of Hydraulic Power Transmission System, 201-bottom, 202-top; the 203-drug storage chamber, joint behind the 204-, 205-front connector; the 206-flow restrictor, 207-base charge hole, 208-piston; 209-pushes bolt, 210-push rod, 211-constant force spring; the 212-protector, 213-cuts off, and 214-pushes at the top bolt perforate; the 215-pressure chamber, 216-charging door, 217-accommodating pressure-transmitting liquid; the 218-micropin, 219-push rod place piston, 220-spring pressure sheet bayonet socket; the 221-interlocking gear, 222-bottom micropin access hole, 223-perfusion mouth rubber blanket; the 224-spring carrier arm; 225-spring fixed bar, 226-fluid passage, 227-observation window.
Fig. 9 is the external structure sketch map that comprises the doser 300 of Hydraulic Power Transmission System provided by the invention.Fig. 9 A is shown as this device unactivated state, and Fig. 9 B is shown as this device and removes protector and active device partition, and Fig. 9 C is shown as this device and is in state of activation.
Figure 10 is the bottom view of doser 300.Figure 10 A is shown as this device and does not remove protector, and Figure 10 B is shown as this device and removes protector.
Figure 11 is the decomposition chart of doser 300.
Figure 12 is the internal structural components figure of doser 300.
Number in the figure is represented: 300-comprises the doser of compressible hydraulic pressure chamber, 301-bottom, 302-top; the 303-drug storage chamber, joint behind the 304-, 305-front connector; the 306-flow restrictor, 307-base charge hole, 308-piston; 309-pushes bolt, 310-fluid reservoir, 311-constant force spring; the 312-protector, 313-cuts off, and 314-pushes at the top bolt perforate; the 315-accommodating pressure-transmitting liquid, 316-micropin, 317-spring fixed bar; 318-spring pressure sheet; the 319-interlocking gear, 320-bottom micropin access hole, 321-perfusion mouth rubber blanket; the 322-charging door; the 323-spring carrier arm, 324-flow restrictor and back connector interface, 325-spring pressure sheet bayonet socket; 326-flow restrictor and pressure chamber interface; the 327-baffle plate, 328-fluid passage, 329-observation window.
Figure 13 is the external structure sketch map that comprises the doser 400 of scalable pressure tube provided by the invention.Figure 13 A is shown as this device unactivated state, and Figure 13 B is shown as this device and removes protector and active device partition, and Figure 13 C is shown as this device and is in state of activation.
Figure 14 is the bottom view of doser 400.Figure 14 A is shown as this device and does not remove protector, and Figure 14 B is shown as this device and removes protector.
Figure 15 is the decomposition chart of doser 400.
Figure 16 is the component drawings of the internal structure of doser 400.
Number in the figure is represented: 400-comprises the doser of scalable pressure tube, 401-bottom, 402-top; the 403-drug storage chamber, joint behind the 404-, 405-front connector; the 406-flow restrictor, 407-base charge hole, 408-piston; 409-pushes bolt, 410-pressure chamber, 411-constant force spring; the 412-protector, 413-cuts off, and 414-pushes at the top bolt perforate; 415-spring pressure sheet bayonet socket, the scalable pressure tube of 416-, 417-micropin; the 418-accommodating pressure-transmitting liquid, 419-spring fixed bar, 420-interlocking gear; 421-bottom micropin access hole, 422-perfusion mouth rubber blanket, 423-push rod; the 424-spring carrier arm; 425-push rod place piston, 426-charging door, 427-observation window.
Figure 17 is the external structure sketch map that comprises the doser 500 of collapsible micropin provided by the invention.Figure 17 A is shown as this device unactivated state, and Figure 17 B is shown as this device and removes protector and active device partition, and Figure 17 C is shown as this device and is in state of activation.
Figure 18 is the bottom view of doser 500.Figure 18 A is shown as this device and does not remove protector, and Figure 18 B is shown as this device and removes protector.
Figure 19 is the decomposition chart of doser 500.
Figure 20 is the cut-away view of doser 500.
Figure 21 is scalable micropin partial structurtes figure in the doser 500.
Number in the figure is represented: 500-comprises the doser of collapsible micropin, 501-bottom, 502-top; the 503-drug storage chamber, joint behind the 504-, 505-front connector; the 506-flow restrictor, 507-base charge hole, 508-piston; 509-pushes bolt; the 510-pressure chamber, the 511-constant force spring, 512-shrinks bolt; 513-cuts off; 514-pushes at the top bolt perforate, 515-accommodating pressure-transmitting liquid, 516-micropin; 517-activates lever; the 518-interlocking gear, 519-bottom micropin access hole, 520-protector; 521-perfusion mouth rubber blanket; the 522-chute, 523-spring pressure sheet bayonet socket, 524-balance pivot; 525-flow restrictor and pressure chamber interface; 526-lever card article, 527-lever rotatable interface, 528-flow restrictor and back connector interface; the 529-charging door; the 530-baffle plate, 531-spring fixed bar, the bolt perforate is shunk at the 532-top; 533-spring pressure sheet; 534-spring carrier arm, 535-shrink bolt and cut off socket, and 536-pushes bolt and cuts off socket; the spacing card article of 537-micropin; 538-lever axis of rotation point, 539-micropin slide slot, 540-micropin medicine feeding hole; the 541-fluid passage, the 542-observation window.
Figure 22 is the external structure sketch map of pre-filled drug storage pipe doser 600 provided by the invention.Figure 22 A is shown as this device unused state, and Figure 22 B is shown as this device and removes protector and active device partition, and Figure 22 C is shown as this device and is in state of activation.
Figure 23 is the bottom view of doser 600.Figure 23 A is shown as this device and does not remove protector, and Figure 23 B is shown as this device and removes protector.
Figure 24 is the decomposition chart of doser 600.
Figure 25 is the internal structural components figure of doser 600.
Number in the figure is represented: the pre-filled drug storage pipe of 600-doser, 601-bottom, 602-top; the pre-filled drug storage pipe of 603-, hydraulic joint behind the 604-, 605-front connector; the 606-flow restrictor, 607-protector, 608-piston; 609-pushes bolt, 610-pressure chamber, 611-constant force spring; the 612-push rod, 613-cuts off, and 614-pushes at the top bolt perforate; the 615-accommodating pressure-transmitting liquid; the 616-spring carrier arm, 617-spring fixed bar, 618-push-rod piston; 619-rubber packing; the 620-interlocking gear, 621-spring pressure sheet bayonet socket, 622-micropin; 623-bottom micropin access hole; drug storage pipe joint behind the 624-, joint flow restrictor interface a behind the 625-, joint flow restrictor interface b behind the 626-; the 627-fluid passage, the 628-observation window.
The specific embodiment
Invention is described
1. definition
Unless otherwise specified, all technology mentioned among the present invention and scientific terminology implication are defined as those of ordinary skill the routine of this term are understood.Mentioned all patents among the present invention, application for patent (deliver or do not deliver) and other publications are all mentioned in citing document.If the patent that the description among the present invention and the present invention quote, application for patent, the opposite or contradiction of the application for patent of having delivered and other publications is as the criterion with the description among the present invention.
Document of being quoted among the present invention or data, neither as paying the utmost attention to, neither be to the perhaps approval of data in it.
Except that specifying, the odd number pronoun in this patent " " " this " includes plural form.
" objective body " in this patent is meant mammal, including, but not limited to, laboratory animal (as mice, rat, Cavia porcellus, primate), house pet (as cat, Canis familiaris L., hamster), farm-animals (as pig, cow, sheep, goat), sports animal (horse), or human." objective body " first-selection is the people.
" paired " " coupling " in this patent is meant directly linking to each other of two inter-modules or linking to each other indirectly by other media.It can be that two assemblies and three of intermediary form an integral body mutually, or two assemblies and an intermediary are attached each other.This connection can be fixed, also can be separable.
" combination " in this patent is meant mechanistic model or adnexa and other components interlocking, pairing, and binding or coupling, unless external force or outside energy are arranged, otherwise can not take apart mutually or break away from.Correspondingly, " removable combination " be meant the mechanical attachment that can be removed or remove.
" liquid communication " in this patent is meant that two or more assemblies directly or indirectly links to each other, and liquid can circulate between them.
" gas communication " in this patent is meant that two or more assemblies directly or indirectly links to each other, and gas can circulate between them.
" isolating fully " and " stoping fully " in the patent are meant medicine in the doser and chemical reactant (solid, liquid and/or gas) are separated fully, to guarantee the safety and the effectiveness of medicine.
" disposable apparatus " in the patent is meant only for an expendable device of patient.
In this patent, carried out sorting out summary to various aspects of the present invention with limited length.Be appreciated that the describing mode that this classification is summed up mainly is brief for the sake of simplicity, do not show the concrete kind that limited field of the present invention is mentioned in only limiting to invent.Therefore, the scope described in the invention should be believed to comprise in all special instruction scopes possible kind, the kind of deriving and individual species.For example, be 1 to 6 with range describe, mean to comprise following scope: 1 to 3,1 to 4,1 to 5,2 to 4,2 to 6,3 to 6 or the like, the independent numeral in this scope is also at these row simultaneously: as 1,2, and 3,4,5,6.This example is not summarized all situations in the whole length only for explanation.
As discussed above, the invention provides a kind of doser of nonrecoverable patch form and by this device, according to the using method of patient's needs infusion predetermined dose of medication.This device has self power, and the adhered layer by bottom of device can attach to skin surface.After device appropriately was fixed on the objective body surface and is activated, device can discharge elastic force as power by constant force spring, and the medicine in the drug storage chamber is injected in the user body by one or more micropins.The size of control motive force can be regulated medicine-feeding rate, makes administration time extend to dozens of minutes, several hours even longer.Can indicate the administration progress by the drug storage chamber position of piston, and judge whether administration is finished.
Can better understanding be arranged to the present invention by accompanying drawing 1-25.Enumerated among the figure several be used for the explanation but unrestriced device design drawing.
Shown in Fig. 1-4, represent to push bolt as the doser 100 of active device to push bolt as active device, only activate and the startup drug release process by this step.Fig. 1 is the external structure sketch map of doser 100, and Figure 1A represents this doser 100 unactivated states.Protector 111 plays the effect of protection micropin, and partition 112 plays to stop pushes bolt 108 by unexpected activated effect.Among Figure 1B, protector 111 and partition 112 are removed.Fig. 1 C shows that pushing bolt 108 is activated.Fig. 2 is that doser 100 has protector 111 in protector 111 (Fig. 2 A) and the same device to be removed the bottom view of back (Fig. 2 B).Fig. 3 is the exploded view in order to explanation doser 100 element.
The doser 100 that Fig. 1-4 shows is a kind of paster dosers.When device was not activated, protector 111 covered doser 100 bottom surfaces, prevents that medicine from overflowing and micropin is stabbed.In case protector 111 is removed, bottom of device 101 and micropin 114 expose, and doser 100 is pasted on the objective body skin surface, and micropin 114 transdermal top layers enter Intradermal.
Simultaneously, doser 100 can be packed in the softish fabric adhesive tape, as adhesive bandage, makes this device feel more comfortable, and profile and conventional pad pasting are more near (not shown).
As shown in Figure 3, doser 100 is to push bolt 108 as active device.Before activating, as activator appliance push bolt 108 by 112 lockings of removable partition, prevent unexpected the activation.Be removed when cutting off 112, push bolt 108 and be pressed, device is activated, and then spring pressure sheet 117 is pushed.Constant force spring 110 is placed on the pressure plate 117 by stretching, extension in advance, by promoting push rod 109 and piston 107, impels the medicinal liquid in the drug storage chamber 103 to enter Intradermal by micropin 114.Drug storage chamber 103 links to each other with back joint 105, and back joint 105 further links to each other with micropin 114 by flow restrictor 115.Medicinal liquid is filled into the drug storage chamber 103 that contains micropin 114 and spring 110 by the charging door 122 that contains perfusion mouth rubber blanket 121.
Device 100 also comprises the shell that is made of top 102 and bottom 101.An interlocking gear 118 is arranged between top 102 and the bottom 101, be used to keep shell mechanism and protection drug storage chamber.Bottom 101 further comprises one and is used for the bottom micropin discrepancy oral pore 119 that micropin 114 is come in and gone out, and the base charge hole 106 that is used for corresponding charging door 122.Watch window 125 is contained at top 102, by the position and then the monitoring administration process of piston 107 in the visual observations drug storage chamber 103.
It is a kind of simple that this model provides, and is applicable to the model equipment of different dosing volume and dosage.Come controlled pressure by adjusting, control the flow velocity of medicinal liquid by the flow restrictor of capillary tube form spring force.
Shown in Fig. 5-8, comprise in the doser 200 of Hydraulic Power Transmission System, between the piston 208 in constant force spring 211 and the drug storage chamber 203 by liquid and flow restrictor mediate contact.Fig. 5 is the external structure sketch map of doser 200.Fig. 6 is that doser 200 has protector 212 in protector 212 (Fig. 6 A) and the same device to be removed the bottom view of back (Fig. 6 B).Fig. 7 is the decomposition texture sketch map in order to explanation doser 200 element.
The doser 200 that Fig. 5-8 shows is a kind of paster dosers.Similar with device 100, when doser 200 was not activated, protector 212 covered device 200 bottoms, prevented that medicine from overflowing and micropin is stabbed.During use, protector 212 is removed, and device is pasted on the objective body skin surface, and micropin sees through objective body skin and enters Intradermal.
As shown in Figure 7, device 200 is that with the main difference of device 100 in the device 200, constant force spring 211 puts on pressure pressure chamber 215 rather than directly puts on push rod.Accommodating pressure-transmitting liquid 217 is connected with piston 208 via fluid passage 226 by flow restrictor 206.The pressure that is produced by spring 211 promotes piston 208 unidirectional moving, and the medicinal liquid in the drug storage chamber 203 is entered in the user body by micropin 218.Before the un-activation, doser 200 is cut off 213 lockings; Device 200 is activated by pushing bolt 209.The constant force spring 211 of pre-elongation brings pressure to bear on push rod 210, and then promotes the medicinal liquid in the drug storage chamber 203.
Device 200 also comprises the shell that is made of top 202 and bottom 201.An interlocking gear 221 is arranged between top 202 and the bottom 201, be used to keep shell and protection drug storage chamber.Bottom 201 further comprises one and is used for the bottom micropin access hole 222 that micropin 218 is come in and gone out, and the base charge hole 207 that is used for corresponding charging door 216.Observation window 227 is contained at top 202, by the position and then the monitoring administration process of the piston in the visual observations drug storage chamber 203 208.
It is a kind of simple that this model provides, and is applicable to the model equipment of different dosing volume and dosage.Come controlled pressure by adjusting, control the flow velocity of medicinal liquid by the flow restrictor of capillary tube form spring force.Flow restrictor is positioned at before the piston, greater flexibility is arranged when selecting accommodating pressure-transmitting liquid, and capillary material and internal diameter also have the bigger range of choice simultaneously, guarantee that further this device can get rid of external environmental interference, the for example influence of temperature and medicinal liquid viscosity provides the stable medicine-feeding rate that continues.
Shown in Fig. 9-12, the doser 300 that comprises compressible hydraulic pressure chamber is represented the similar model of another kind of and doser 200.The fluid reservoir 310 of doser 300 can be compressed under constant force spring 311 effects.Fig. 9 is the external structure sketch map of doser 300, and Figure 11 is the decomposition texture sketch map in order to explanation doser 300 each element.
The doser 300 that Fig. 9-12 shows is a kind of paster dosers.Similar with device 200, when device was not activated, protector 312 covered bottom of device, prevents that medicine from overflowing and micropin is stabbed.During use, protector 312 is removed, and device is pasted on the objective body skin surface, and micropin sees through objective body skin and enters Intradermal.
As shown in figure 11, doser 300 is that with the main difference of doser 200 in the device 300, constant force spring 311 puts on pressure the fluid reservoir 310 that can compress.Accommodating pressure-transmitting liquid 315 is connected with piston 308 via fluid passage 328 by flow restrictor 306.The pressure that is produced by constant force spring 311 promotes piston 308 unidirectional moving via accommodating pressure-transmitting liquid 315, and the medicinal liquid in the drug storage chamber 303 is entered in the user body by micropin 316.Before the un-activation, device is cut off 313 lockings; Device 300 is activated by pushing bolt 309.The constant force spring 311 of pre-elongation brings pressure to bear on spring pressure sheet 318, and then promotes the medicinal liquid in the drug storage chamber 303.
It is a kind of simple that this model provides, and is applicable to the model equipment of different dosing volume and dosage.Come controlled pressure by adjusting, control the flow velocity of medicinal liquid by the flow restrictor of capillary tube form spring force.Flow restrictor 306 is used to control the flow velocity of accommodating pressure-transmitting liquid 315 and then controls medicine-feeding rate indirectly.Flow restrictor is positioned at before the piston, greater flexibility is arranged when selecting accommodating pressure-transmitting liquid, and capillary material and internal diameter also have the bigger range of choice simultaneously, guarantee that further this device can get rid of external environment, the for example influence of temperature and medicinal liquid viscosity provides the stable medicine-feeding rate that continues.Device 300 another advantages are to adopt compressible hydraulic pressure chamber, can better control the volume of whole device.
Shown in Figure 13-16, the doser 400 that comprises scalable pressure tube is similar to device 200 on structural design, and difference is that in the doser 400, scalable pressure tube 416 directly links to each other with piston 408.Figure 13 is the external structure sketch map of doser 400, and Figure 15 is the decomposition texture sketch map in order to explanation doser 400 each element.
The doser 400 that Figure 13-16 shows is a kind of patch-type dosers.Similar to device 200, protector 412 covers doser 400 bottoms, prevents that medicine from overflowing and the generation of micropin injury accident.Protector 412 is removed, install 400 Pastings in the objective body skin surface, micropin 417 passes objective body skin and enters Intradermal.
As shown in figure 15, doser 400 is that with the different of doser 200 the scalable pressure tube 416 in the device 400 directly links to each other with piston 408.Accommodating pressure-transmitting liquid 418 communicates with piston 408 by flow restrictor 406.The pressure that constant force spring 411 produces expands scalable pressure tube 416 and launches, and impels piston 408 unidirectional moving, and makes the medicinal liquid in the drug storage chamber 403 pass through micropin 417 target approach bodies.Doser 400 is activated by pushing bolt 409, and 411 pairs of push rods 423 of constant force spring of tensioning are in advance exerted pressure, and with the pressure transfer of accommodating pressure-transmitting liquid 418 to piston 408.
Drug storage chamber 403 combines with micropin 417 by front connector 405.Medicinal liquid carries out liquid medicine filling by the charging door that contains perfusion mouth rubber blanket 422 426 that is positioned at back joint 404.
It is a kind of simple that this model provides, and is applicable to the model equipment of different dosing volume and dosage.The pressure of spring depends primarily on capillary flow restrictor, can control medicine-feeding rate by regulating this pressure.Thereby flow restrictor 406 can be controlled the flow velocity that the flow velocity of accommodating pressure-transmitting liquid 418 is controlled medicinal liquid indirectly.The position of flow restrictor makes the kind of accommodating pressure-transmitting liquid and flow restrictor more flexible in the selection of material/diameter, has guaranteed that further medicine-feeding rate receiving environmental effect, keeps constant during as the viscosity change of temperature and medicinal liquid.Another advantage of doser 400 is that the scalable pressure tube that is connected with piston can reduce the volume of accommodating pressure-transmitting liquid device, better the size of control device.
Shown in Figure 17-21, the doser 500 that comprises collapsible micropin contains the regracting micropin.Figure 17 is the external structure sketch map of doser 500, and Figure 19 is the decomposition texture sketch map in order to explanation doser 500 each element.
The doser 500 that Figure 17-21 shows is a kind of paster dosers.Different with above device, device 500 micropins that contain 516 have scalable function.Protector 520 is used to protect micropin.During use, protector 520 is removed, and device is pasted on the objective body skin surface.Push bolt 509 by activation, micropin 516 sees through objective body skin and enters Intradermal; After being used to complete, shrink bolt 512 by pushing, micropin shrinks back bottom of device shell 501, prevents the generation of micropin injury happenstance.
Device 500 is that with the difference of other designs this device micropin 516 can stretch, so micropin can be in two kinds of positions.In the position for the moment, it is back and invisible that micropin 516 is withdrawn into bottom of device shell 501.This moment, drug storage chamber 503 was disconnected with the fluid passage 541 of micropin 516, and medicinal liquid can't be by micropin 516 by infusion; When position two, micropin 516 stretches out and thrusts skin.Drug storage chamber 503 is connected with micropin 516 by front connector 505.Under this situation, medicinal liquid is transfused in the user body.
Press and push bolt 509, micropin 516 one moves to position two from the position.An end that activates lever 517 links to each other with micropin 516, and the other end links to each other with spring pressure sheet bayonet socket 523.Lever card article 526 is used to stop the constant force spring 511 of tensioning in advance to shrink; Push bolt 509 and can play the effect of opening lever card article 526 equally, when depress push bolt 509 after, constant force spring 511 brings pressure to bear on accommodating pressure-transmitting liquid 515; Accommodating pressure-transmitting liquid 515 brings pressure to bear on the piston 508 by flow restrictor 506, and then the medicinal liquid in the drug storage chamber 503 is injected in the user body by micropin 516.
The active device of device 500 is for pushing bolt 509.Push before bolt 509 un-activations, device is cut off 513 lockings.Cut off with contraction bolt 512 and combine, can prevent in the administration process, the bounce back generation of incident of micropin.
Doser 500 also comprises the shell that is made of top 502 and bottom 501.An interlocking gear 518 is arranged between top 502 and the bottom 501, be used to keep shell and protection drug storage chamber 503.Bottom 501 further comprises one and is used for the bottom micropin access hole 519 that micropin 516 is come in and gone out, and the base charge hole 507 that is used for corresponding charging door 529.Observation window 542 is contained at top 502, by the position and then the monitoring administration process of visual observations piston 508.
Shown in Figure 22-25, pre-filled drug storage pipe doser 600 is similar to doser 200 on structural design, and difference is, contains pre-filled drug storage pipe 603 in the doser 600.Figure 22 is the external structure sketch map of doser 600.Figure 23 is that doser 600 has protector 607 in protector 607 (Figure 23 A) and the same device to be removed the bottom view of back (Figure 23 B).Figure 24 is the decomposition texture sketch map in order to explanation doser 600 element.Figure 25 is the internal structure sketch map of doser 600.
The pre-filled drug storage pipe doser 600 that Figure 22-25 shows is a kind of dosers that contain pre-filled drug storage pipe 603.When device was not activated, protector 607 covered doser 600 bottoms 601, prevents that medicine from overflowing and micropin is stabbed.During use, protector 607 is removed, and device is pasted on the objective body skin surface, and micropin sees through objective body skin and enters Intradermal.
In the doser 600, flow restrictor 606 is installed in the pressure chamber 610.Flow restrictor 606 links to each other by back joint flow restrictor interface a 625 with back hydraulic joint 604, links to each other by back joint flow restrictor interface b 626 with back drug storage pipe joint 624.Back drug storage pipe joint 624 is used to install pre-filled drug storage pipe 603.Accommodating pressure-transmitting liquid 615 is full of pressure chamber 610 and back hydraulic joint 604, is connected with push-rod piston 618 via fluid passage 627.
Liquid drug in advance in the pre-filled drug storage pipe 603, piston 608 and rubber packing 619 stop medicinal liquids to overflow.When pre-filled drug storage pipe 603 linked to each other with front connector 605, micropin 622 entered in the pre-filled drug storage pipe by rubber packing 619, finishes the medicinal liquid flow pass.
Constant force spring 611 puts on pressure chamber 610 by push rod 612 with pressure.The pressure that is produced by constant force spring 611 promotes push-rod piston 618 unidirectional moving, and the medicinal liquid in the pre-filled drug storage pipe 603 is entered in the user body by micropin 622.Before the un-activation, device is cut off 613 lockings; Doser 600 is activated by pushing bolt 609.The constant force spring 611 of pre-elongation brings pressure to bear on push rod 612, and then promotes the medicinal liquid in the pre-filled drug storage pipe 603.
This model provides a kind of model equipment that is used to install pre-filling drug liquid tube.By with medicinal liquid filling in advance, can simplify production technology, improve the storage time of power set, guarantee quality of liquid medicine.Pre-filled drug liquid tube model equipment provides Production and Packaging mode more easily for the pharmaceutical production merchant.
Although each mounted cast described above has characteristics design separately, for example scalable micropin, the installation site of flow restrictor, compressible hydraulic pressure chamber, and scalable pressure tube and pre-filled drug storage pipe, be appreciated that, more than described separately only for illustrative purposes, more than each in the design or combination all can merge in the same device design.
2. micropin:
The micropin part includes an empty micropin that is connected with drug storage chamber at least.During administration, micropin part and contact skin, transdermal top layer.
Similar to hypodermic needle, this doser contains a micropin at least.In some applications, this device can contain microneedle array, and this array may contain 2,3,4,5 or more micropins, is used for increasing absorption area in same administration time, improves medicine-feeding rate and administration volume.
The length of micropin is determined by the use approach.For subcutaneous injection or infusion, micropin length can be greater than 3-5mm.For intradermal injection or infusion, micropin length is less than 2mm, or less than 1mm, or less than 0.5mm.The length of micropin and shape without limits, first-selected small gauge needle, 31G-36G micropin for example, minute hand pain and tissue injury are littler relatively.
Micropin can be made by various materials, comprises plastic material and natural or artificial macromolecular materials such as rustless steel, silicon dioxide, glass, titanium, Merlon or poly-malonate.Certainly, more than enumerate kind and incomplete, the material of other suitable micropin manufacturings also can use.
3. drug storage chamber:
Need the medicinal liquid of infusion to be stored in the specific cavity, this cavity and micropin partly have fluid passage, with between the spring pressure by liquid medium or directly contact with spring pressure.In some concrete enforcements, drug storage chamber and pressure chamber are separated by removable, gastight piston, and under pressure, piston moves along drug storage chamber, and the medicinal liquid that promotes in the drug storage chamber enters in patient's body by micropin.
In some concrete enforcements, drug storage chamber is designed to column; In some concrete enforcements, drug storage chamber and micropin contact portion are designed to taper to reduce dead volume.
In some concrete enforcements, drug storage chamber length is obviously greater than its internal diameter.In some concrete enforcements, drug storage chamber is designed to tubular structure, and pipe range and bore ratio are between 2: 1 to 1000: 1, more preferably between 10: 1 to 500: 1.The length of drug storage chamber and diameter mainly depend on the volume that needs the infusion medicinal liquid.In some concrete enforcements, between the 10mm, more preferably 2mm is between the 4mm at 0.2mm for the drug storage chamber internal diameter.In some concrete enforcements, drug storage chamber volume scope at 20 μ L between the 10ml, more preferably at 10 μ L between the 10ml, can satisfy the demand of most injectable drugs.
In some concrete enforcements, utilize this device, by increasing drug storage chamber and pressure apparatus, make apparatus of the present invention also can be used as the infusion of larger volume medicinal liquid.This device can be used for making the doser of the portable controllable type large volume medicinal liquid of clinical use, for example venous transfusion device.
There are strict requirements for the drug storage chamber material therefor of need long term storage medicinal liquid.I class glass since its inertia, impermeability and with the compatibility of most medicines, be the first-selected drug storage material of atarax class medicine.Yet, because the fragility of glass material needs drug storage chamber associated components to be arranged to guarantee the integrity of glass medicine storage device.Usually, tubulose or column glass tubing have better choice.
In some concrete enforcements, drug storage chamber can be made by other materials, cyclisation polyolefin for example, ACLAR, Merlon, polyethylene, polypropylene, polrvinyl chloride, polyvinylidene chloride, polyester, polyamide, fluoropolymer polymer, polyurethane, lactoprene, titanium, aluminum.The cyclisation polyolefin has been used to the atarax medicine, and has shown good compatibility.Above material has better pliability, can be at the requirement of container shapes.
In some concrete enforcements, in same doser, a plurality of drug storage chambers can be installed independently, while two or more medicines of infusion, and do not need various medicament mixed.These two or more drug storage chambers can link to each other with same pressure chamber, obtain similar motive force.Perhaps, depend on different infusion requirements, in same device, two or more independent pressure chamberes can be respectively link to each other with independent drug storage chamber.For example, Pramlintide usually is administered for treating diabetes with insulin combination, and present patient need distinguish insulin injection and Pramlintide when using.In this device, adopt the design of binary drug storage chamber, just can pass through an independent operation, simultaneously insulin injection and Pramlintide.
4. motive force
Doser can use polytype driving force or power generation arrangement, comprises elastomeric material, spring, and atmospheric pressure, battery or chemical reaction produce gas, marmem or turbine.In some concrete enforcements, use constant force spring to produce driving force.By spring steel or stainless steel strip are carried out cure process, make it to form the clockwork spring that closely curls, pressure can be provided; Compare with other elastic cords or compression spring, constant force spring can provide constant compression force and then obtain stable promotion speed.Constant force spring can be single head or double end.
The material of constant force spring has multiple choices, and commonly used is carbon steel, rustless steel or alloy.The elastic force that constant force spring provides can in very large range be selected according to instructions for use.
5. flow restrictor
Doser among the present invention adopts the built-in pressure apparatus of constant force spring.In concrete enforcement, the pressure stable and then the generation that provide by constant force spring continue constant medicine-feeding rate.
In some concrete enforcements, doser need provide the administration time of a few hours even tens of hours, therefore need further control flow velocity by flow restrictor.Flow restrictor adopts the capillary tube with narrow and small internal diameter usually.
The laminar flow behavior of liquid in tubular conduit meets Poiseuille ' s formula, and according to this formula, flow rate of liquid is directly proportional with the pressure differential at passage two ends, the biquadratic of caliber, is inversely proportional to pipe range and liquid viscosity.
Based on above formula, when fluid temperature or viscosity changed, same spring motive force can produce different flow velocitys.Based on above reason, doser needs in liquid medicine flow, passages the medicine-feeding rate of flow restrictor to obtain envisioning to be installed usually.This design is in order to tackle the change in flow that viscosity or temperature change bring.
In some concrete enforcements, flow restrictor is installed between pressure apparatus and the drug storage chamber, by the liquid transfering pressure in the pressure chamber.This design allows to select and merges to use same full-bodied liquid (for example liquid paraffin) as the pressure conductive liquid, changing the influence that stable rate of releasing drug is brought with assurance medicinal liquid viscosity can ignore, and reduces the influence of variation of ambient temperature to medicine-feeding rate as far as possible.Simultaneously, this design is by changing the viscosity of conductive liquid, and the range of choice of flow restrictor is had further expansion.
The pressure conductive liquid has high coefficient of viscosity, and the coefficient of viscosity temperature influence is as far as possible little simultaneously.
Flow restrictor can be by having certain pliability (for example plastics) but not dilatable under pressure material.
6. active device
The energy drives doser that the present invention produces by constant force spring.In concrete enforcement, spring is in tense situation in advance; Activate this pressure apparatus by active device.
In some concrete enforcements, can by user before using to the constant force spring application of force.Although this can increase the operating procedure of user, can guarantee the stability of elastic force.
In some concrete enforcements, active device can be controlled the flexible of doser micropin.In use, active device makes micropin thrust; Same, after administration was finished, active device made micropin bounce back the safety of assurance device by same mechanism.
7. indication
In some concrete enforcements, can monitor the administration performance by the perusal position of piston.In some concrete enforcements, in labelling or graduated position, indicate the administration situation by piston.
8. piston:
As mentioned above, piston be as physical barriers with drug blockage in drug storage chamber, simultaneously as promoting the unidirectional mobile device of medicinal liquid.In certain embodiments, plunger designs is similar to the syringe piston of routine use.
Piston is made by rubber usually, to guarantee its air-tightness and elasticity.
9 device administration covering scopes:
In concrete enforcement, the medicine in the device comprises that all can be by the medicine of drug administration by injection.
In concrete enforcement, the pharmaceutical pack in the device is meant that further those need the medicine of percutaneous dosing or are easy to the medicine of first pass metabolism or cause tangible gastrointestinal tract or the medicine of liver side effect or be difficult for absorbed medicine or the medicine of needs change pharmacokinetics feature.
In concrete enforcement, medicine can comprise some small-molecule drugs, as androgen, and estrogen, testosterone, nitroglycerin, nicotine, antihypertensive, A Xiluowei, alprazolam, aspirin, aldosterone, atenolol, azithromycin, azidothymidine AZT, penicillin, bacitracin, benzylpenicillin, caffeine, candoxatril, captopril, carbamazepine, chloromycetin, cimetidine, clonidine, cephamycin, Ciclosporin A, haloperidol, desipramine, dexamethasone, danazol, diazepam, voltaren see diclofenac, diltiazem, ketorolac, amycin, epinephrine, enalapril maleate, Abboticine, clindamycin, famotidine, felodipine, fluorouracil, flurbiprofen, hydrochlorothiazide, furosemide, norepinephrine, ibuprofen, imipramine, Itraconazole, labetalol, lisinopril, methotrexate, metoprolol, nadolol, naloxone, nortriptyline, omeprazole, phenytoin, piroxicam, prazosin, prostaglandin, macrolide, medrat, Progesterone, medroxyprogesterone, monobactam, aztreonam, propranolol, quinidine, ranitidine, scopolamine, tenidap, terfenadine, trovafloxacin, valproic acid, vinblastine, Ziprasidone, rapamycin, ketoconazole, steroid, prednisone, triamcinolone, ketoprofen, naproxen, Nifedipine, prostaglandin, Alprostadil, misoprostol, riboflavin, levodopa, furosemide, fentanyl, lignocaine, selegiline, tetracaine, rotigotine, methylphenidate, estradiol-, nortriptyline, Propranolol, potassium nitrate, megestrol, buprenorphine, morphine, meglumine antimony, lisuride, granisetron, BUP, cis-N-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl, benzene (uncle) butylamine, tulobuterol, atenolol, cimetidine, ranitidine, terbutaline, the L-DOPA, madopar, phenylalanine, phenazone, and their salt, congener and derivant.
In concrete enforcement, medicine generally includes some macromolecular drugs such as protein, polypeptide, saccharide, nucleotide, lipid, carbohydrate and their complex.
In concrete enforcement, protein drug can be antifibrin-ferment, albumin, α-1 proteolytic enzyme, antihmemophilic globulin, coagulation factor, antibody, anti-CD 20 antibodies, anti-CD 52 antibody, the anti-CD 33 immunotoxin, the DNA enzyme, erythropoietin, the IX factor, the VII factor, the VIII factor, follicle stimulating hormone, granulocyte colony-stimulating factor G-CSF, the G-CSF of grafting PEG, α or beta galactosidase, glucagon, glucocerebrosidase, granulocyte-macrophage colony-stimulating factor, chorionic-gonadotropin hormone, hepatitis B antigen, hbs antigen, hepatitis B core antigen, the hepatitis B envelope antigen, hepatitis C antigen, hirudin, anti-HER-2 antibody, AIA, anti-IL-2 receptor antibody, insulin, insulin Glargine, Insulin Aspart, insulin lispro, interferon, the interferon of grafting PEG, α or α 2a or α 2b interferon, β or β-1a or β-1b interferon, interferon gamma, interleukin II, interleukin 11, interleukin 12, LH Luteinizing hormone, Nesiritide, Osteogenic Protein-1, BMP-2, the Lyme vaccine, platelet-derived somatomedin, antiplatelet antibody, anti-sarcoma virus antibody (annti-RSV), growth hormone, D2E7, the anti-tumor necrosis factor receptor fusion protein, tissue plasminogen activator, TNK-tPA, thyrotropin, fibrinolytic enzyme, thrombus dissolving enzyme, ADA Adenosine deaminase, the ADA Adenosine deaminase of PEGization, anistreplase, asparaginase, Collagenase, streptokinase, saccharase, urokinase, press down the phthalein enzyme, Botulinum toxin, fibroblast growth factor, endothelial cell growth factor (ECGF), snake venom etc.Said albumen comprises from modes such as gene recombinaton, chemosynthesis or biological extraction and obtaining.Albumen comprises the analog of mutant, modification or derivant etc. simultaneously.Proteic initial source can be human or other species.
In some concrete enforcements, can use peptide class of the present invention comprises: thyroliberin (ACTH), the angiogenesis inhibitor polypeptide, adamtsostatin, adiponectin, adipokinetic hormone, fat connects plain, fat triglyceride fat (fat) enzyme, adrenomedullin, the agouti associated protein, the alarin vasoactive peptide, allatostatin, amelogenin, calcitonin, dextrin, amyloid, angiogenin, angiotensin, cause the peptide of becoming thin, the antiinflammatory peptide, the diuresis factor, antimicrobial peptide, apelin, peptide antibiotics, the RGD peptide, atrial natriuretic peptide, atriopeptin, auriculin, autocrine motility factor, Magainin, bombinakinin, Kallidin I, brain natriuretic peptide, Brain Derived Neurotrophic Factor, frog antibacterial peptide, the C peptide, caspase is restrained the factor, pancreas [gland] peptide, buccalin, bursin, C type natriuretic peptide, the calcitonin related peptides, the calcitonin receptor kassinin kinin, calmodulin, CART, cartilostatin, casomokinin, a cheese deltorphin delta, catestatin, cathepsin, attacin, cerebellin, chemerin, chelocystokinin, chromograin, ciliary neurotrophic factor, conotoxin peptide, aconopressin, conotoxin, and Copeptin, CASH, corticotropin-releasing factor, the cortex chalone, coupling factor, sozin, delta EEG, dermorphin, vassopressin, the desamino vassopressin, diuretic hormone, dynorphin, endokinin, interior morphine peptide, endorphins, endostatin, Endothelin, enkephalin, enterostatin, exendin, Exenatide, the erythropoiesis peptide, epithelium growth factor, fat directed peptide, galanin, gastric inhibitory polypeptide, Gastrin., gastrin releasing peptide, growth hormone-releasing peptide, glucagon, glucagon like peptide, the Agifutol derivant, deltorphin delta outside the glutenin source, somatotropin releasing factor, granulocyte-macrophage colony-stimulating factor is restrained peptide, growth hormone peptide, the guanylin peptide, the HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) peptide, helodemine, tachykinin, hepatitis c virus peptide, the hepatitis B phallotoxins, the HSV peptide, the herpesvirus peptide, hirudin, HIRULOG, insulin like growth factor, hydrin, melanotropin, kassinin, keratinocyte growth factor, kinetensin, kininogen, the kiss peptide, kyotorphin, the laminin peptide, the Leptin peptide, leucokinin, leucopyrokinin, leupeptin, gonadotropin releasing hormone, lymphokines, melanin-concentrating hormone and inhibitor thereof, melanotropin discharges inhibitor, the melanotropin intensifier, morphine is regulated neuropeptide, MSH, neoendorphin, nesfatin, neurokinin, neuromedin, neuropeptide tyrosine, neurotensin, neurotrophic factor, nociceptin, the fat element of restraining, opiate receptor antagonist, aricine, salmon calcitonin see calcimar, oxytocin, pancreastatin, peptide YY, physalaemin sample peptide, secretin, Somat, the seminal fluid activating peptide, the P material, syndyphalin, thrombin is responsive plain, thymopoietin, thymosin, throtropin releasing hormone, transforming growth factor, tuftsin, tumor necrosis factor or related peptides, usrechistachykinin, 17-hydroxy-11-dehydrocorticosterone, the urotensin antagonist, valorphin, vasotocin, vasoactive intestinal peptide, peptide antibiotics, xenopsin or related peptides, said peptide class comprises from gene recombinaton, mode such as chemosynthesis or biological extraction obtains.Peptide comprises the analog of mutant, modification or derivant etc. roughly the same the time.The source can be human or other species.
The bioactive macromolecule that relates in the invention comprises from adenovirus, anthrax, tuberculin, Botulinum toxin, cholera, diphtheria toxoid, diphtheria and tetanus toxoid, diph-tet and pertussis, haemophilus B, hepatitis A, hepatitis B virus, influenza, encephalitis, measles, parotitis, rubella, meningococcus, pestilence, pertussis, streptococcus pneumoniae, poliomyelitis, rabies virus, rotavirus, rubella, variola, tetanus toxoid, typhoid fever, chickenpox, yellow fever, the vaccine that extracts in bacterial antigen and the compound substance.
In certain embodiments, bioactive macromolecule comprises from chamber dirt mice, animal scurf, mycete, pollen, hogweed, rubber, wasp, the deutero-allergen of insecticide, reaches the allergen of selecting the compound substance.
Bioactive macromolecule mentioned above generally all exists with molecule family, comprises having the natural molecular structure and the chemical compound of sequence, and through the analog of structure or sequence modification, and through chemistry or the outside analog of modifying of biological method.
For example, " GLP-1 promoter " its scope of mentioning before this comprises the complex that activates people GLP-1 receptor wholly or in part.The glucagon-like peptide 1 (GLP-1) that L-cell in the intestinal discharges can increase the insulin response behind oral glucose or the fat.GLP-1 peptide and its variant, analog and derivant are the same.For example the GLP-1 peptide comprises natural glucagon like peptide, blocks, and extends sudden change or other mutational variety.Analog comprises ZP10A or BIM-51077, GLP-1 or with the analog of polyethylene glycol polymeric, the analog that GLP-1 or itself and albumin merge, or with chemically combined analog such as liraglutide, CJC-1131.Equally, extendin-4 (having another name called exenatide) is a GLP-1 promoter, and it and it analog all belongs to this scope.Exenatide, exenaide analog (United States Patent (USP) 7,329,646 have reported) and long-acting conjugated body such as CJC-1134 belong to glucagon like peptide and/or its derivant.It is unlikely to get rid of all analog, and present invention also is not limited to above-mentioned these that mention.
10. pharmaceutical formulation is formed
In concrete enforcement, the medicine in apparatus of the present invention is a liquid dosage form.Aqueous solution, non-aqueous solution, suspension, Emulsion, gel and emulsifiable paste all are the pharmaceutical dosage forms that is suitable for; Can produce the suitable selection that consists of that continues release of active agent.
Solution and suspension generally are by water (for example sterilized water or apirogen water), or water and biocompatible mutual solvent (for example ethanol, propylene glycol or Polyethylene Glycol such as PEG 400) are prepared.
The adjuvant that may also comprise other in solution and the suspension, antiseptic (as benzalkonium chloride) for example, solubilizing agent/surfactant (as Tween 80, sorbester p17, benzalkonium chloride), buffer agent, isoosmotic adjusting agent (as sodium chloride), and thickening agent.May also contain suspending agent (as microcrystalline Cellulose and sodium carboxymethyl cellulose) in the suspension.
Comprise medicine and the adjuvant that can form suspension with the medicine complete miscibility in the aqueous suspension, adjuvant commonly used has: suspending agent, for example carboxymethyl hydroxylated cellulose, methylcellulose, hydroxypropyl cellulose, sodium alginate, polyvidon, tragakanta, arabic gum; Dispersant or wetting agent, be generally natural phospholipid, as lecithin, alkylene oxide fatty acid condensation substance (Myrj 45), oxirane and long-chain fatty alcohol condensation substance, the condensation substance (octadecanoic acid ester of polyethylene glycol) of oxirane and fatty acid hexose alcohol ester, or the condensation substance of oxirane and the own dextran sulfate sodium of fatty acid (polyethylene sorbester p17).May also contain one or more antiseptic (as ethyl, n-propyl group, p-hydroxybenzoate) and coloring agent in the aqueous suspension.
Oil suspension is that medicine is suspended in vegetable oil (as Oleum Arachidis hypogaeae semen, olive oil, Oleum sesami, Oleum Cocois, liquid Paraffin).Oil suspension also contains thickening agent, as Cera Flava, and paraffin or hexadecanol.Can add a kind of antioxidant such as vitamin C in addition.
Drug component among the present invention also may be O/W.The oil phase composition can be a vegetable oil, and for example olive oil and Oleum Arachidis hypogaeae semen can be mineral oil, and for example liquid paraffin also can be above-mentioned miscella.The emulsifying agent that is fit to can be natural gum, and for example arabic gum or tragacanth gum can be natural phospholipid, for example soybean phospholipid, lecithin, esters, or isolating ester in the fatty acid can be hexitan, for example span can be the condensation substance of ester and oxirane, for example tween.Also can contain sweeting agent and spice in the emulsifying agent.
11. using method
The invention provides and a kind of doser is attached to patient skin surface, start active device and device is maintained skin surface and enter intravital medication fully up to the effective dose of medicine thing, this device can be attached on the skin with hands or with device fitting.
In some concrete enforcements, this doser can be used for Intradermal, and is subcutaneous, muscle, the injection of vein or other approach or transfusion.For example, venous transfusion needs special-purpose infusion set usually, to the also constraint to some extent of action of objective body.By enlarging the volume and the pressure apparatus of drug storage chamber, this device can be used as portable venous transfusion device, and transfusion volume and infusion rate can be regulated.Objective body utilizes this device, can be free movable during infusing.
The problem that micropin faces when using mainly is the compression to skin histology, has greatly limited medicine-feeding rate.Bounce back slightly after micropin thrusts and to alleviate this problem.In some concrete enforcement, micropin tilts to enter skin with certain angle can alleviate elastic force, and the angle of inclination is big more, and tissue bounce-back resistance is more little.Go into the pin angle by enlarging, can increase side tension force, reduce direct resistance, solve the problem of micropin administration.
Although this device desire reaches the purpose of Wicresoft by using micropin, also can adopt other types such as intravenous needle, scalp acupuncture with the prolongation administration time, thereby improve effect of drugs.For example, when coming control of diabetes patient's basic blood sugar level, need stable medicine-feeding rate and long administration time by replenishing basal insulin.Utilize the device that the small dimension micropin is housed among the present invention, can finish the administration process of insulin solutions easily.Although than micropin, injury subcutaneous or the intramuscular injection micropin increases to some extent, but consider other remarkable advantages, for example can reduce risk of hypoglycemia by controlled rate of release, improve aspects such as drug effect, comprehensively more factors is selected and is not only limited to and micropin when selecting micropin.
12. medicine box
The invention provides a kind of medicine box that contains doser.Doser in some medicine box can the preliminary filling medicine.And other solids or freeze-dried drug can be contained in one independently in the container, before administration by the liquid medium dissolving and rapidly in the injection device.
Except doser and medicine, this medicine box also comprises some other components, for example operation instructions; prevent that the stand-by protection that micropin damages from pasting; stop the standby active device of reaction unit accidental activation to cut off, device is adhered to standby adhesion layer on the skin and the processing bag after using.In some concrete enforcements, medicine box includes nonrecoverable doser for once using adnexa.
List of references
1.Prausnitz，M.R.，Microneedles?for?transdermal?drug?delivery.Adv?Drug?Deliv?Rev，2004.56(5)：p.581-7.
2.Vandervoort，J.and?A.Ludwig，Microneedles?for?transdermal?drug?delivery：a?minireview.Front?Biosci，2008.13：p.1711-5.
3.McAllister，D.V.，et?al.，Microfabricated?needles?for?transdermal?delivery?of?macromoleculesand?nanoparticles：fabrication?methods?and?transport?studies.Proc?Natl?Acad?Sci?U?S?A，2003.100(24)：p.13755-60.
4.Davis，S.P.，et?al.，Hollow?metal?microneedles?for?insulin?delivery?to?diabetic?rats.IEEE?TransBiomed?Eng，2005.52(5)：p.909-15.
5.Mikszta，J.A.，et?al.，Protective?immunization?against?inhalational?anthrax：a?comparison?ofminimally?invasive?delivery?platforms.J?Infect?Dis，2005.191(2)：p.278-88.
6.Alarcon，J.B.，et?al.，Preclmical?evaluation?of?microneedle?technology?for?intradermaldelivery?of?influenza?vaccines.Clin?Vaccine?Immunol，2007.14(4)：p.375-81.
7.Martanto，W.，et?al.，Microinfusion?using?hollow?microneedles.Pharm?Res，2006.23(1)：p.104-13.
8.Roxhed，N.，et?al.，Painless?drug?delivery?through?microneedle-based?transdermal?patchesfeaturing?active?infusion.IEEE?Trans?Biomed?Eng，2008.55(3)：p.1063-71.
9.Good，B.T.，C.N.Bowman，and?R.H.Davis，A?water-activated?pump?for?portable?microfluidicapplications.J?Colloid?Interface?Sci，2007.305(2)：p.239-49.
10.Good，B.T.，C.N.Bowman，and?R.H.Davis，An?effervescent?reaction?micropump?for?portablemicrofluidic?systems.Lab?Chip，2006.6(5)：p.659-66.
Referenced patents or patent application:
United States Patent (USP) 3964482,5250023,5957895,6503231,6656147,6743211,6780171,6623457,6960193,6939324,7047070,6808506,7083592,7115108,7156838,7250037,7410476,7429258; U.S. Patent application 20080215015; PCT patent WO03/022330, WO02/002179, WO03/024507, WO04/033021, WO06/054280, WO06/132602; Chinese patent CN02812823.0; European patent application EP 1925333.
Claims (22)
1. doser of giving the objective body medication is characterized in that this device comprises:
A) micropin;
B) be closed in one or more drug storage chambers in the device, fluid path arranged between drug storage chamber and the micropin and contain the medicine of being sent;
C) be closed in pressure apparatus in the device, pressure apparatus or and drug storage chamber between fluid path is arranged or directly acts on piston in the fluid reservoir;
D) be used for the active device of starting pressure device, active device is designed to the primary importance and the second position, has an active device to cut off between the primary importance and the second position; When active device when primary importance moves to the second position, pressure apparatus is activated;
E) be positioned at the piston of drug storage chamber, piston is unidirectional to be moved along with pressure increases;
F) comprise a removable protector that invests the device outside, in order to prevent the syringe needle injury;
G) comprise an adhered layer that is positioned at bottom of device, be used to stick in the objective body skin surface;
H) pressure apparatus that is closed in the device is a constant force spring.
2. doser according to claim 1 is characterized in that, drug storage chamber is cylindric.
3. doser according to claim 2 is characterized in that, drug storage chamber height and internal diameter ratio are between 2: 1 to 1000: 1.
4. doser according to claim 1 is characterized in that, between drug storage chamber and the pressure chamber jointing is arranged.
5. doser according to claim 1 is characterized in that, drug storage chamber comprises one and be used for pouring into the inlet that needs the infusion medicinal liquid in drug storage chamber.
6. doser according to claim 1 is characterized in that, active device is to do the combination of selecting one or more devices the valving of power and the heater from pushing pin device, wrench device, pull unit, battery.
7. doser according to claim 1 is characterized in that, active device comprises an active device and cuts off, and is used to guarantee that active device remains on primary importance, prevents that active device from moving to the second position by primary importance.
8. doser according to claim 1 is characterized in that, comprises a flow restrictor between drug storage chamber piston and the pressure apparatus.
9. doser according to claim 1 is characterized in that, doser comprises a watch window, is used for monitoring the situation of movement of piston at drug storage chamber.
10. a doser of giving the objective body medication is characterized in that, comprises to patient's two administrations of at least two kinds of medicines of infusion simultaneously and divides device, comprising:
A) first and second micropin;
B) first administration divides the drug storage chamber of device inside, between first drug storage chamber and first micropin fluid passage is arranged, and contains the first kind of medicine that is useful on infusion;
C) second administration divides the drug storage chamber of device inside, between second drug storage chamber and second micropin fluid passage arranged, and contains the second kind of medicine that is useful on infusion;
D) be closed in first administration and divide first pressure apparatus in first pressure chamber in the device, first pressure apparatus or and fluid reservoir between fluid path is arranged or directly acts on piston in the fluid reservoir;
E) be closed in second administration and divide second pressure apparatus in second pressure chamber in the device, second pressure apparatus or and fluid reservoir between fluid path is arranged or directly acts on piston in the fluid reservoir;
F) active device is used for starting first pressure apparatus in first pressure chamber and second pressure apparatus in second pressure chamber; Active device has the primary importance and the second position, has an active device to cut off between the primary importance and the second position; When primary importance moved to the second position, the pressure apparatus in first pressure chamber and second pressure chamber was activated with active device;
G) first drug storage chamber and second drug storage chamber have a piston respectively, piston is under the pressure effect of first pressure chamber and the increase of second pressure chamber, unidirectional respectively moving completely cuts off the medicine in the medicine in first fluid reservoir and second drug storage chamber and first pressure chamber and second pressure chamber.
H) comprise a removable protector that invests the device outside, in order to prevent the syringe needle injury;
I) comprise an adhered layer that is positioned at bottom of device, be used to stick in the objective body skin surface;
J) pressure apparatus that is closed in the device is a constant force spring.
11. doser according to claim 10 is characterized in that, wherein second kind of medicine in first kind of medicine in first drug storage chamber and second drug storage chamber is identical or different.
12. doser according to claim 10 is characterized in that, wherein first kind of pressure apparatus and second kind of pressure apparatus are identical or different.
13., it is characterized in that this device is disposable use according to claim 1 or 10 described dosers.
14. the using method of doser according to claim 1 is characterized in that,
A) device is sticked on the objective body skin surface;
B) by active device is moved to the second position from primary importance, the starting pressure device, simultaneously
C) assurance device is pasted on the objective body skin surface all the time, in treatment effective dose of medicine thing input objective body body.
15. the using method of doser according to claim 10 is characterized in that,
A) device is sticked on the objective body skin surface;
B), start first pressure apparatus in first pressure chamber and second pressure apparatus in second pressure chamber by active device is moved to the second position from primary importance;
C) assurance device is pasted on the objective body skin surface all the time, in two kinds of medicine input objective body bodies of treatment effective dose.
16. the using method according to claim 14 or 15 described dosers is characterized in that, device is sticked on before the objective body skin surface, removes protector.
17. the using method according to claim 14 or 15 described dosers is characterized in that, further comprises, active device is moved to the second position from primary importance before, remove active device and cut off.
18. the using method according to claim 14 or 15 described dosers is characterized in that, selectable infusion of drug approach comprises: Intradermal infusion, h inf, intramuscular infusion and venoclysis.
19., it is characterized in that there is medicine box the doser outside according to claim 1 or 10 described dosers.
20. doser medicine box according to claim 19 is characterized in that comprising in the medicine box stand-by protection and pastes, and is used to prevent unexpected syringe needle injury.
21. doser medicine box according to claim 19 is characterized in that comprising in the medicine box a standby active device and cuts off, and is used to prevent that doser from being activated by accident.
22. doser medicine box according to claim 19 is characterized in that, comprises a standby adhered layer in the medicine box, is used for doser is pasted on the objective body skin surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910048805A CN101850153A (en) | 2009-04-03 | 2009-04-03 | Disposable drug administration device with own power |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910048805A CN101850153A (en) | 2009-04-03 | 2009-04-03 | Disposable drug administration device with own power |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101850153A true CN101850153A (en) | 2010-10-06 |
Family
ID=42801939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910048805A Pending CN101850153A (en) | 2009-04-03 | 2009-04-03 | Disposable drug administration device with own power |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101850153A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972499A (en) * | 2010-11-10 | 2011-02-16 | 吉林大学 | Easy painless drug delivery device |
| CN106176572A (en) * | 2016-08-19 | 2016-12-07 | 中山大学 | A kind of microneedle array plaster and preparation method thereof |
| CN106267464A (en) * | 2015-05-25 | 2017-01-04 | 美敦力公司 | Hydraulic, fluid infusion device and manufacture method thereof |
| WO2017071035A1 (en) * | 2015-10-31 | 2017-05-04 | 深圳市易特科信息技术有限公司 | Military portable patch syringe |
| CN109125851A (en) * | 2018-09-28 | 2019-01-04 | 遵义医学院附属医院 | A kind of medical use instillator |
| CN109996582A (en) * | 2016-07-25 | 2019-07-09 | 休曼商业有限公司 | Skin hand syringe |
| CN113384373A (en) * | 2013-11-05 | 2021-09-14 | 辛纳吉勒公司 | Device and method for continuous drug delivery via the oral cavity |
| US11426376B2 (en) | 2015-05-06 | 2022-08-30 | Synagile Corporation | Devices for the administration of pharmaceutical suspensions |
| CN115120854A (en) * | 2022-07-04 | 2022-09-30 | 奥格生物技术（六安）有限公司 | Natural direct administration method for prostate |
| WO2023011622A1 (en) * | 2021-08-06 | 2023-02-09 | Medtrum Technologies Inc. | Half-press-free drug infusion device |
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2009
- 2009-04-03 CN CN200910048805A patent/CN101850153A/en active Pending
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101972499B (en) * | 2010-11-10 | 2016-07-06 | 吉林大学 | Easy painless drug delivery device |
| CN101972499A (en) * | 2010-11-10 | 2011-02-16 | 吉林大学 | Easy painless drug delivery device |
| CN113384373A (en) * | 2013-11-05 | 2021-09-14 | 辛纳吉勒公司 | Device and method for continuous drug delivery via the oral cavity |
| CN113384373B (en) * | 2013-11-05 | 2022-10-21 | 辛纳吉勒公司 | Device and method for continuous drug delivery via the oral cavity |
| US11426376B2 (en) | 2015-05-06 | 2022-08-30 | Synagile Corporation | Devices for the administration of pharmaceutical suspensions |
| CN106267464A (en) * | 2015-05-25 | 2017-01-04 | 美敦力公司 | Hydraulic, fluid infusion device and manufacture method thereof |
| WO2017071035A1 (en) * | 2015-10-31 | 2017-05-04 | 深圳市易特科信息技术有限公司 | Military portable patch syringe |
| CN109996582A (en) * | 2016-07-25 | 2019-07-09 | 休曼商业有限公司 | Skin hand syringe |
| CN109996582B (en) * | 2016-07-25 | 2021-09-03 | 休曼商业有限公司 | Hand-operated syringe for skin |
| CN106176572A (en) * | 2016-08-19 | 2016-12-07 | 中山大学 | A kind of microneedle array plaster and preparation method thereof |
| CN109125851A (en) * | 2018-09-28 | 2019-01-04 | 遵义医学院附属医院 | A kind of medical use instillator |
| WO2023011622A1 (en) * | 2021-08-06 | 2023-02-09 | Medtrum Technologies Inc. | Half-press-free drug infusion device |
| CN115120854A (en) * | 2022-07-04 | 2022-09-30 | 奥格生物技术（六安）有限公司 | Natural direct administration method for prostate |
| CN115120854B (en) * | 2022-07-04 | 2023-10-13 | 奥格生物技术（六安）有限公司 | Natural direct administration device for prostate |
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Application publication date: 20101006 |