CN107913458B

CN107913458B - Liquid quantitative storage system

Info

Publication number: CN107913458B
Application number: CN201610883811.XA
Authority: CN
Inventors: 徐百; 吴国林
Original assignee: Suzhou Natong Bio Nano Technology Co ltd
Current assignee: Suzhou Natong Bio Nano Technology Co ltd
Priority date: 2016-10-10
Filing date: 2016-10-10
Publication date: 2021-04-06
Anticipated expiration: 2036-10-10
Also published as: CN107913458A

Abstract

The invention discloses a liquid quantitative storage system, which comprises a liquid outlet end and a liquid storage tank with an openable end, wherein the upper surface of the liquid outlet end is provided with a micro device and a plastic piece, the micro device is only used for penetrating through the horny layer of skin, the plastic piece is provided with a prefabricated liquid outlet hole and a liquid groove communicated with the prefabricated liquid outlet hole, and the micro device is adhered to the surface of the plastic piece; the liquid reservoir is filled with liquid, and the openable end of the liquid reservoir is connected with the liquid outlet end. The invention provides a novel administration method between the traditional injection and the traditional transdermal administration, and the medicine permeation and absorption are better. And the plastic part is pre-perforated and then communicated with the liquid storage tank, so that the preparation process is greatly simplified, and the production cost is reduced. In addition, the nano solid microneedle or the nano solid microneedle array can not generate a liquid leakage phenomenon, and simultaneously can accurately control the dosage.

Description

Liquid quantitative storage system

Technical Field

The invention relates to the technical field of transdermal drug delivery, in particular to a liquid quantitative storage system.

Background

Currently, in the technical field of transdermal drug delivery, nano microneedles or nano wafers are widely used. The nanometer chip is a nanometer permeation promoting special tool developed according to the structure of human skin and is formed by carving monocrystalline silicon through a nanometer technology process. The surface of the nanometer wafer is a series of micro needle arrays which can open the outermost horny layer of the skin without hurting the dermis layer, thereby greatly improving the nutrient permeability. The biological compatibility of the monocrystalline silicon ensures the safety of the nanocrystalline in the use process. The nano microneedle is a microneedle which opens a skin pipeline through a nanotechnology, a needle head is similar to a small wafer square, dense and thin invisible small needles are fully distributed on the microneedle, and the small square is pressed on the skin, so that the medicine can enter the epidermis, and people hardly feel the medicine.

At present, the nano-micro-needle mainly comprises a solid micro-needle and a hollow micro-needle. The solid micro-needle administration mode is mainly divided into two steps, namely firstly coating liquid medicine and then punching, or firstly punching and then coating the medicine. For example, patent publication No. CN103079634B, discloses a built-in non-verbal instructional device that can be integrated into an applicator by applying the agent either pre-or post-perforation. However, since transdermal and drug delivery are performed separately in the whole process, the osmotic absorption of the drug is affected to some extent, which makes such products less than ideal in terms of use efficiency and drug effect.

As for hollow microneedles, many of the prior arts have been used, such as patent publication No. CN102497909B entitled "hollow microneedle array", which discloses a hollow microneedle for delivering a liquid. However, such hollow microneedles are relatively expensive to manufacture, relatively low in yield, and relatively low in yield. More importantly, because the administration position is shallow, the leakage of liquid is often caused after injection, and the dosage cannot be accurately controlled.

Therefore, the present inventors have earnestly demanded to conceive a new technology to improve the problems thereof.

Disclosure of Invention

The invention aims to provide a liquid quantitative storage system which can realize synchronous administration, obviously improve the administration efficiency and reduce the production and preparation cost.

In order to solve the technical problems, the technical scheme of the invention is as follows:

a liquid dosing storage system comprising: the liquid outlet end and a liquid storage with an openable end are arranged, the upper surface of the liquid outlet end is provided with a micro device and a plastic piece, the micro device is used for only penetrating through the horny layer of the skin, the plastic piece is provided with a prefabricated liquid outlet hole and a liquid groove communicated with the prefabricated liquid outlet hole, and the micro device is adhered to the surface of the plastic piece; the liquid reservoir is internally provided with liquid, and the openable end of the liquid reservoir is connected with the liquid outlet end.

Preferably, the length of the microdevice that penetrates the stratum corneum is between 4 microns and 2000 microns.

Preferably, the micro device is a nano solid microneedle or a nano solid microneedle array.

Preferably, the liquid storage comprises a first storage and a second storage, the front end of the first storage is provided with the liquid outlet end, and the second storage is communicated with the first storage.

Preferably, a prefabricated liquid outlet hole is formed in the center of the plastic part, and the liquid groove is cross-shaped or annular and is communicated with the prefabricated liquid outlet hole.

Preferably, the volume of liquid contained within the liquid reservoir is from 0.01mL to 100 mL.

Preferably, the liquid is a nutrient solution or a liquid medicine.

Preferably, the first storage is made of soft materials, the second storage is made of hard materials, and the first storage and the second storage are connected in a sleeved mode.

Preferably, the first storage is made of hard materials, the second storage is made of soft materials, and the first storage and the second storage are connected in a sleeved mode.

By adopting the technical scheme, the invention at least comprises the following beneficial effects:

1. the liquid quantitative storage system combines the medicine and the administration device together, and has a simpler and more reasonable structure. The method is characterized in that the nano solid micro-needle is arranged on the surface of the skin surface, and the nano solid micro-needle is in contact with the skin and simultaneously discharges liquid, so that the use is more convenient. More importantly, the drug penetration and absorption are better.

2. According to the liquid quantitative storage system, the plastic part is provided with the hole in advance, and then the plastic part is communicated with the liquid storage, so that the preparation process is greatly simplified and the production cost is reduced on the premise of ensuring smooth introduction of liquid.

3. According to the liquid quantitative storage system, the stratum corneum is opened through the nano solid micro-needle or the nano solid micro-needle array, liquid is slowly controlled, liquid leakage is avoided, dosage can be accurately controlled, and manufacturing cost is reduced.

Drawings

FIG. 1 is a schematic diagram of a liquid quantitative storage system according to the present invention;

FIG. 2 is a schematic structural view of a plastic article according to the present invention;

FIG. 3 is a schematic diagram of the present invention;

FIG. 4 is a graph of permeability versus time for experiment two.

Wherein: 1. the liquid storage device comprises a liquid storage, 11, a first storage, 12, a second storage, 2, a liquid outlet end, 21, a plastic part, 22, a prefabricated liquid outlet hole, 23, a liquid flowing groove and 3, a shell.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Referring to fig. 1, a liquid quantitative storage system according to the present invention includes: the device comprises a liquid outlet end 2 and a liquid storage 1 with an openable end, wherein the upper surface of the liquid outlet end 2 is provided with a micro device and a plastic part 21, the micro device is used for only penetrating through the horny layer of skin, the plastic part 21 is provided with a prefabricated liquid outlet hole 22 and a liquid groove 23 communicated with the prefabricated liquid outlet hole, and the micro device is adhered to the surface of the plastic part 21; the liquid reservoir 1 is internally provided with liquid, and the openable end of the liquid reservoir is connected with the liquid outlet end 2; the fluid reservoir 1 is connected under pressure to an actuating arm (omitted from the drawings, but known to those skilled in the art). The openable end is automatically opened by the actuating arm so that the openable end is communicated with the prefabricated liquid outlet hole 22, and liquid is caused to sequentially pass through the openable end, the prefabricated liquid outlet hole 22 and the micro device. Trigger through pressure promptly, then drive the vibration of cavity head through drive mechanism, then because inertial effect, can throw out liquid. Namely, one side of the microneedle touches the skin and goes out liquid at the same time. Compared with the traditional microneedle with one side and the other side for liquid discharge, the use is more convenient.

Preferably, the length of the microdevice that penetrates the stratum corneum is between 4 microns and 2000 microns. Preferably, the length of the microdevice that penetrates the stratum corneum is between 4 microns and 500 microns. More preferably, the microdevice has a length that penetrates between 20 microns and 100 microns into the stratum corneum layer of the skin.

Preferably, the micro device is a nano solid microneedle or a nano solid microneedle array. Different from hollow microneedles, the nano solid microneedles or the nano solid microneedle arrays have the advantages of low manufacturing cost, high yield and high qualification rate, and the administration position and the administration precision can be accurately controlled.

Preferably, the liquid reservoir 1 comprises a first reservoir 11 and a second reservoir 12, the liquid outlet end 2 is arranged at the front end of the first reservoir 11, and the second reservoir 12 is communicated with the first reservoir 11.

Preferably, as shown in fig. 2 (omitting the micro-device), a preformed liquid outlet 22 is provided at a central portion of the plastic part 21, and the liquid groove 23 is in a cross shape or ring shape (the cross shape is shown in the drawings, but the ring shape is known to those skilled in the art and will not be described in detail) and is communicated with the preformed liquid outlet 22. As is well known, in the prior art, the holes are mainly drilled on the nano-wafer, so that the preparation difficulty is high, and the damage of the micro-needles and the like is easily caused, so that the processing and preparation costs are too high. The application develops a new method, the plastic part 21 is perforated in advance and then is communicated with the liquid storage tank 1, the preparation process is greatly simplified on the premise of ensuring the smooth introduction of liquid, and the production cost is reduced.

Preferably, the volume of the liquid contained in the liquid reservoir 1 is 0.01mL to 100 mL. More preferably, the volume of liquid contained in the liquid reservoir 1 is 0.01mL to 1 mL.

Preferably, the viscosity of the liquid is between 0.00001Pa and 5 Pa.

Preferably, the liquid is a nutrient solution or a liquid medicine.

Preferably, the first storage 11 is made of a soft material, the second storage 12 is made of a hard material, and the first storage 11 and the second storage 12 are connected in a sleeved manner.

Preferably, the first storage chamber 11 is made of a hard material, the second storage chamber 12 is made of a soft material, and the first storage chamber 11 and the second storage chamber 12 are connected in a sleeved manner.

The hard material can be ABS, POM, PS, PMMA, PC, PET, PBT, PPO material and the like, and the soft material can be soft PVC, K glue (BS), TPE, TPR, EVA, TPU material and the like. The materials of the first reservoir 11 and the second reservoir 12 are selected for convenience in connection with the first reservoir and the second reservoir, and the manufacturing cost is low. Of course, other connection methods, such as clamping, suction connection, welding, and integration, can be implemented and are within the scope of the present embodiment.

In a preferred embodiment, as shown in fig. 3, it includes a housing 3, a transmission mechanism and a power mechanism are disposed in the housing 3, and the transmission mechanism is driven by the power mechanism to generate linear motion; the cavity head is connected with the shell 3 and is connected with the transmission mechanism under the action of pressure.

The working principle of the embodiment is as follows: the method of activating the vibration with a preset pressure ensures that the user can only press vertically when using the device, but not slide on the skin. The skin can be protected from scratches and injuries. And when the vibration, because the effect of inertia, can throw off liquid, the air can get into simultaneously, so like this, the liquid of liquid reservoir 1 can last out, and it is clean to all liquid shifts, so need not to design special play liquid device. The amount of liquid discharged in a single vibration can be accurately controlled between 0.01mL and 100 mL.

The invention combines the medicine and the administration device together, and has simpler and more reasonable structure. And the mode of administration is changed greatly, a novel administration method between the traditional injection and the traditional transdermal administration is provided, namely, the liquid is delivered to the surface of the epidermis of the skin from the liquid storage 1 in a mode similar to the injection, is diffused through the epidermis and is absorbed through the epidermis (or enters the blood circulation of a human body). Due to the setting of the synchronous administration mode, the nano solid microneedle can discharge liquid when contacting skin, and the use is more convenient. More importantly, the drug penetration and absorption are better. In addition, the cuticle is opened through the nano solid microneedle or the nano solid microneedle array, liquid is slowly controlled, the liquid leakage phenomenon is avoided, meanwhile, the dosage can be accurately controlled, and the manufacturing cost is reduced.

The liquid quantitative storage system can greatly improve the transdermal administration efficiency and quality, and experiments are used for illustration.

Experiment I, the mechanical instrument of the invention is matched with a vibration mechanism, 2mL of physiological saline is filled in the cavity head, the cavity head is arranged at a vertical downward position, a vibration mode is not started, and liquid does not naturally flow out due to gravity. When the power switch is turned on, the cavity head is in contact with the skin of a human body, and the cavity head is activated to vibrate 5000 times per minute, liquid is naturally transferred to the surface of the skin from the liquid storage 1 in the cavity head, and the liquid transfer speed can be adjusted through the size of the pore passage of the prefabricated liquid outlet hole 22 and the vibration frequency. Table 1 shows the time required for complete transfer of the liquid at different frequencies, where the pore size is 1 mm.

TABLE 1

Frequency (times/second)	Transfer time (minutes)
		65	25
83	18
		100	15

Experiment two, this experiment compared the transdermal absorption of self-formulated lidocaine gels after treatment without and with the nano-wafers for 20 seconds. Taking pig ears in a refrigerator, taking the skin with the thickness of 800 μm, and removing the hair on the surface until the skin is smooth. After PBS (7.4) is soaked for 10-15 minutes, the materials are cut into the size of the outer edge of a receiving pool, a nano chip set is processed by the system (the nano chip with the lattice height of 150 microns) of the invention and a vibration mechanism for 20s,the mixture was placed between a receiving well and a dosing well and equilibrated for 1h with PBS (7.4) at 37. + -. 0.2 ℃. Using Franze diffusion cell, the dosage is 120mg, the receiving cell volume is 2.5mL, and the actual transdermal area is 0.66cm²The receiver was PBS (7.4), temperature 37. + -. 0.2 ℃ and magnetic stirring 280 rmp.

As can be seen from fig. 4 (wherein diamond-solid is a nano-chip group, and ■ is a control group), no nano-chip was used, the transdermal effect of lidocaine was poor, and less than 5% of lidocaine could be absorbed through skin; after the nano-chip synchronous administration, the transdermal effect of the lidocaine gel is obviously improved. Most unexpectedly, despite the higher viscosity of the lidocaine gel, it was still possible to transfer from the invented liquid reservoir 1 to the skin surface via mechanical action within 40 seconds and to quantify the transdermal penetration, with successful detection of the lidocaine drug in the receiving reservoir.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A liquid dosing system, comprising: the liquid outlet end and a liquid storage with an openable end are arranged, the upper surface of the liquid outlet end is provided with a micro device and a plastic piece, the micro device is used for only penetrating through the horny layer of the skin, the plastic piece is provided with a prefabricated liquid outlet hole and a liquid groove communicated with the prefabricated liquid outlet hole, and the micro device is adhered to the surface of the plastic piece; the liquid storage is internally provided with liquid, an openable end of the liquid storage is connected with the liquid outlet end, a transmission mechanism and a power mechanism are arranged in a shell of the liquid quantitative storage system, and the transmission mechanism generates linear motion under the driving of the power mechanism; the liquid storage is connected with the transmission mechanism under the action of pressure, and when the liquid quantitative storage system discharges liquid, a method of activating the power mechanism to vibrate by using preset pressure is adopted, so that only vertical pressing can be ensured during use.

2. The liquid metered dose storage system of claim 1 wherein: the length of the microdevice that penetrates the stratum corneum layer of the skin is between 4 microns and 2000 microns.

3. The liquid quantitative storage system as set forth in claim 1 or 2, wherein: the micro device is a nano solid microneedle or a nano solid microneedle array.

4. The liquid quantitative storage system as set forth in claim 1 or 2, wherein: the liquid storage comprises a first storage and a second storage, the front end of the first storage is provided with the liquid outlet end, and the second storage is communicated with the first storage.

5. The liquid metered dose storage system of claim 3, wherein: the liquid storage comprises a first storage and a second storage, the front end of the first storage is provided with the liquid outlet end, and the second storage is communicated with the first storage.

6. The liquid metered dose storage system of claim 2, wherein: the central part of the plastic part is provided with a prefabricated liquid outlet, and the liquid groove is in a cross shape or an annular shape and is communicated with the prefabricated liquid outlet.

7. The liquid metered dose storage system of claim 1 wherein: the volume of the liquid contained in the liquid reservoir is 0.01mL to 100 mL.

8. The liquid metered dose storage system of claim 1 wherein: the liquid is nutrient solution or liquid medicine.

9. The liquid metered dose storage system of claim 4, wherein: the first storage warehouse is made of soft materials, the second storage warehouse is made of hard materials, and the first storage warehouse and the second storage warehouse are connected in a sleeved mode.

10. The liquid metered dose storage system of claim 4, wherein: the first storage warehouse is made of hard materials, the second storage warehouse is made of soft materials, and the first storage warehouse and the second storage warehouse are connected in a sleeved mode.

11. The liquid metered dose storage system of claim 5, wherein: the first storage warehouse is made of soft materials, the second storage warehouse is made of hard materials, and the first storage warehouse and the second storage warehouse are connected in a sleeved mode.

12. The liquid metered dose storage system of claim 5, wherein: the first storage warehouse is made of hard materials, the second storage warehouse is made of soft materials, and the first storage warehouse and the second storage warehouse are connected in a sleeved mode.