Device for measuring residence time of nasal preparation in nasal mucosa

Abstract

The utility model discloses a device for measuring the residence time of a nasal preparation in nasal mucosa, which comprises a test plate with a plurality of test channels, a constant-temperature base and optionally a transparent cover body. The test channel is covered with a carrier for bearing nose simulation liquid, the constant-temperature base is hollow, a water inlet is formed in one side of the bottom end of the constant-temperature base, a water outlet is formed in one side of the top end of the constant-temperature base, so that a constant-temperature medium can pass through, and a device for displaying temperature is arranged on the test plate or the constant-temperature base. By adopting the novel device for measuring the residence time of the nasal preparation in the nasal mucosa, the nasal cavity environment including temperature, humidity, mucosa surface liquid composition, the inclination angle between the nasal cavity structure and the face and the like can be simulated to a certain extent, and prescription comparison with high flux and good parallelism can be carried out, so that development and evaluation of the nasal preparation are efficiently assisted.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of biological medicine, specifically, relate to a research and development device, particularly specifically, relate to a device for measuring the residence time of nasal preparation in nasal mucosa. BACKGROUND

[0002] Nasal preparation refers to the biological product directly used in the nasal cavity, which can not only play a local role in treating diseases such as rhinitis, but also can be absorbed across the membrane to treat systemic or even brain diseases. Compared with oral administration, nasal administration can avoid drug degradation in gastrointestinal fluid and liver first-pass effect, has high bioavailability, and the bioavailability of small molecule drugs is close to intravenous injection. Compared with injection administration, nasal administration is convenient to use, can be self-administered, has light or no damage to the body, has good patient compliance, and is suitable for long-term administration of non-cilia toxic and irritating drug preparations, and can reduce the spread of infectious diseases. At the same time, it is also suitable for patients who cannot take oral administration due to various reasons. Therefore, nasal preparation has broad application prospects.

[0003] In the research and development process of nasal preparation, the residence time of nasal mucosa is an important influencing factor of the drug efficacy after the nasal preparation plays a local or transmucosal absorption. The existing technology Development of in vitro models to demonstrate the ability of PecSys, an in situ nasal gelling technology, to reduce nasal run-off and drip, literature source: Drug Development and Industrial Pharmacy, 2013; 39(5): 816-824, is simulated by a nasal 3D model or a TLC plate. The former is not convenient for rapid screening in the formulation research stage, and the latter has poor simulation of the nasal environment and structure.

[0004] A device is developed, which can simulate the nasal environment to a certain extent, including temperature, humidity, mucosal surface liquid composition, nasal structure and inclination angle of the face, and can also be high-throughput and repeatable for formulation comparison, thereby efficiently assisting the development and evaluation of nasal preparation. UTILITY MODEL CONTENT

[0005] In view of the above problems, the utility model provides a device for measuring the residence time of nasal preparation in nasal mucosa, which can efficiently assist the development and evaluation of nasal preparation.

[0006] The utility model adopts the following technical scheme: a device for measuring the residence time of nasal preparation in nasal mucosa, comprising a test plate and a constant temperature base, optionally further comprising a cover body.

[0007] Preferably, the test plate is provided with one or more test channels; further preferably, the test plate is provided with a scale and / or a sample application point, most preferably, the test channels are in communication with the sample application point.

[0008] Preferably, the test plate is selected from a ground glass plate or a stainless steel plate.

[0009] Preferably, the upper layer of the test channel is covered with a carrier which is impregnated with a nasal simulation fluid, the carrier is selected from one of filter paper, filter membrane or biological mucosa, and the carrier is impregnated with the nasal simulation fluid.

[0010] Preferably, the test channels on the test plate are separated by a partition, the partition can be provided above the carrier; or the partition is directly provided on the test plate, the partition can be integrally formed with the test plate or detachably connected to the test plate, in which case the carrier is provided in the plurality of test channels; or the test channel is a concave groove, and the carrier is provided in the groove.

[0011] Preferably, one side of the thermostat base is an inclined surface for placing the test plate, one end of the bottom of the thermostat base is provided with a liquid inlet, and one end of the top of the thermostat base is provided with a liquid outlet, to facilitate the circulation of the thermostat medium.

[0012] Preferably, the test plate is detachably connected to the inclined surface of the thermostat base.

[0013] Preferably, the cover is hollow.

[0014] Preferably, the cover is made of transparent material, such as transparent glass or transparent plastic.

[0015] Preferably, the cover can only cover the test plate, or the cover can cover the thermostat base.

[0016] Preferably, the temperature of the thermostat medium is between 32-37℃, such as 32℃, 33℃, 34℃, 35℃, 36℃, 37℃ or any value between them, to simulate the nasal environment and obtain more accurate results.

[0017] Preferably, the thermostat medium is thermostat water, and a circulating pump is used to circulate the thermostat water in the thermostat base to maintain the constant temperature.

[0018] Preferably, the angle of the inclined surface of the thermostat base is 60°, to better simulate the nasal environment.

[0019] Preferably, the device for measuring the nasal retention time of nasal preparations also comprises a temperature measuring and displaying mechanism, which is provided on the test plate or the thermostat base, to facilitate temperature detection and display.

[0020] Compared with the prior art, the utility model has the advantages that,

[0021] 1, adopt the technical scheme of the utility model, can in the development evaluation of preparation, more accurate determination of the retention time of nasal preparation in nasal mucosa, and not affected by the environment temperature.

[0022] 2, adopt this new type's accurate measurement nasal preparation in nasal mucosa retention time's device, can avoid the problem of inaccurate measurement caused by nasal simulation liquid or nasal preparation volatilization in the air.

[0023] 3, adopt this new type's measurement nasal preparation in nasal mucosa retention time's device, can measure the retention of multiple samples simultaneously, complete the repeatability evaluation of same prescription, or comparison and screening of different prescriptions.

[0024] 4, according to the in-vivo and in-vitro simulation, adjust the type of simulation liquid or replace the filter membrane, artificial membrane, biological mucosa, further establish the flow or adhesion index related to in-vivo and in-vitro. BRIEF DESCRIPTION OF DRAWINGS

[0025] Other features, objects and advantages of the utility model will become more apparent through reading the following detailed description of non-restrictive embodiments with reference to the accompanying drawings:

[0026] Figure 1 It is the schematic diagram of test board;

[0027] Figure 2 It is the schematic diagram of the device for measuring the retention time of nasal preparation in nasal mucosa without cover;

[0028] Figure 3 It is the schematic diagram of the device for measuring the retention time of nasal preparation in nasal mucosa with cover. DETAILED DESCRIPTION

[0029] The technical scheme will be described in detail below in combination with specific embodiments. The following embodiments are exemplary and will help the person skilled in the art to further understand the present application, but do not limit the present application in any form. It should be pointed out that, for those skilled in the art, without departing from the inventive concept, a number of changes and improvements can be made. These all belong to the protection scope of the utility model.

[0030] In the present patent application, the nasal simulation liquid can be commercially available or prepared by oneself, which is not limited here; for example, the composition of the nasal simulation liquid can be: 0.04M K+(KCl), 0.15M Na+(NaCl), 0.005M Ca2+(CaCl2) aqueous solution. The exemplary preparation method is to first weigh 3.02g of potassium chloride, 8.77g of sodium chloride, and 0.6026g of calcium chloride, then add water to 1L, shake and ultrasonic to completely dissolve, and obtain.

[0031] The utility model provides a kind of device for measuring nasal preparation in nasal mucosa residence time, as shown in Figure 1 、 Figure 2 And Figure 3 As shown, including test plate 1, constant temperature base 2, optionally, it also includes cover 3;The test plate setting 1 or multiple test channels 12;The test plate has scale and sample adding point 11, and the test channel 12 is communicated with sample adding point 11.

[0032] In one embodiment, the upper layer of the test plate 1 is covered with a carrier soaked in the nasal simulation liquid, and the carrier is selected from filter paper, filter membrane or biological mucosa.

[0033] In one embodiment, the test channels 12 on the test plate 1 are separated from each other by a partition, which can be arranged above the carrier;Or the partition is directly arranged on the test plate, and the partition can be integrally formed with the test plate or detachably connected, and at this time the carrier is arranged in the plurality of test channels 12;Or the test channel 12 is arranged as a concave groove, and the carrier is arranged in the groove;It is well known to those skilled in the art that there are many ways to arrange the test channel 12, which is not limited here for the purpose of enabling the nasal preparation to move along a straight line rather than an inclined line.

[0034] In one embodiment, the test plate 1 is selected from a ground glass plate or a stainless steel plate, which is not limited in the utility model.

[0035] In one embodiment, one side of the constant temperature base is an inclined surface for placing the test plate 1;The constant temperature base 2 is hollow, and one end of the bottom of the constant temperature base 2 is provided with a liquid inlet 21, and one end of the top of the constant temperature base 2 is provided with a liquid outlet 22, so as to facilitate the passage of constant temperature medium;The side surface of the constant temperature base 2 can also have two inclined surfaces for the purpose of increasing test efficiency.

[0036] In one embodiment, the test plate 1 is detachably connected to the inclined surface of the constant temperature base 2, and the connection mode is not limited, which can be various modes such as bonding, clamping, etc.

[0037] In one embodiment, the cover 3 is hollow, which can cover only the test plate 1 or the thermostat base 2, and the purpose is to keep temperature and prevent the nasal simulation liquid or the nasal preparation from evaporating.

[0038] In one embodiment, the cover 3 is made of transparent material, such as transparent glass or transparent plastic, which is beneficial for observation and recording of the behavior of the nasal preparation, and for taking pictures or videos at regular intervals and completing the measurement comparison.

[0039] In one embodiment, the temperature of the thermostat medium is between 32-37℃, such as 32℃, 33℃, 34℃, 35℃, 36℃, 37℃ or any value between them, which is used to simulate the nasal cavity environment and obtain more accurate results.

[0040] In one embodiment, the thermostat medium is thermostat water, and a circulating pump is used to circulate the thermostat water in the thermostat base to maintain constant temperature.

[0041] In one embodiment, the angle of the inclined surface of the thermostat base is 60°, which is used to better simulate the nasal cavity environment; the angle of the inclined surface can also be set to other angles according to other purposes, which is a routine operation for those skilled in the art, and is not limited herein.

[0042] In one embodiment, the device for measuring the retention time of the nasal preparation in the nasal mucosa further comprises a temperature measuring and displaying mechanism 13, which is arranged on the test plate 1 or the thermostat base 2.

[0043] The use method of the utility model comprises the following main steps:

[0044] Step 1: Start the circulating water pump to make the water at a specific temperature enter the thermostat base, so that the thermostat base 2 reaches the set temperature;

[0045] Step 2: Cover the carrier soaked in the nasal simulation liquid on the upper layer of the test channel 12 of the test plate 1, and fix it, and drop the nasal preparation at the sample adding point 11 of the test plate 1;

[0046] Step 3: Place the test plate 1 on the inclined surface of the thermostat base 2, and cover the cover 3; the connection between the cover 3 and the thermostat base 2 adopts a method known to those skilled in the art, such as clamping, etc., which can meet the purpose of being convenient to open and close without affecting the test.

[0047] Step 4: Observe and record the behavior of the nasal preparation through the cover 3.

[0048] In the description of the present application, it needs to be understood that the terms "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0049] The specific embodiments of the present application are described above. It needs to be understood that the present application is not limited to the specific embodiments described above, and various changes or modifications can be made by those skilled in the art within the scope of the claims, which does not affect the essential content of the present application. In the case of no conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.

Claims

1. An apparatus for determining the residence time of nasal preparations on the nasal mucosa, characterized in that, Includes a test plate and a constant temperature base; or, includes a test plate, a constant temperature base, and a cover. The test board is equipped with one or more test channels; One side of the constant temperature base is an inclined surface for placing the test plate, and the test plate is detachably connected to the inclined surface of the constant temperature base; or, The cover covers the test plate; or, the cover covers the constant temperature base.

2. The apparatus according to claim 1, characterized in that, The test plate has a scale. And / or, the test plate has sample application points; And / or, the test channel is connected to the sample application point; And / or, the test plate is selected from frosted glass plate or stainless steel plate.

3. The apparatus according to claim 2, characterized in that, The upper layer of the test channel is covered with a carrier soaked in nasal simulated liquid, the carrier being selected from filter paper, filter membrane or biological mucosa.

4. The apparatus according to claim 3, characterized in that, The test channels on the test board are separated from each other by partitions, which are positioned above the carrier. Alternatively, the partition can be directly mounted on the test plate, with the partition being integrally formed with or detachably connected to the test plate, in which case the carrier is disposed in multiple test channels; Alternatively, the test channel is a concave groove, and the carrier is disposed in the groove.

5. The apparatus according to claim 1, characterized in that, The thermostatic base is hollow, with a liquid inlet at one end of the bottom and a liquid outlet at one end of the top, for containing the thermostatic medium.

6. The apparatus according to claim 1, characterized in that, The cover is hollow; Alternatively, the cover may be made of a transparent material.

7. The apparatus according to claim 6, characterized in that, The cover is made of transparent glass or transparent plastic.

8. The apparatus according to claim 5, characterized in that, The temperature of the constant temperature medium is between 32 and 37°C.

9. The apparatus according to claim 8, characterized in that, The temperature of the constant temperature medium is selected from 32℃, 33℃, 34℃, 35℃, 36℃ or 37℃ or any value between the two.

10. The apparatus according to claim 9, characterized in that, The constant temperature medium is constant temperature water, and a circulating pump is used to circulate the constant temperature water in the constant temperature base.

11. The apparatus according to claim 1, characterized in that, The angle of the inclined surface of the constant temperature base is 60°.

12. The apparatus according to claim 1, characterized in that, The device also includes a mechanism for measuring and displaying temperature, which is disposed on the test plate or on the thermostatic base.

Images