CN107305181A - A kind of method for studying percutaneous dosing solvent penetration - Google Patents
A kind of method for studying percutaneous dosing solvent penetration Download PDFInfo
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- CN107305181A CN107305181A CN201610242209.8A CN201610242209A CN107305181A CN 107305181 A CN107305181 A CN 107305181A CN 201610242209 A CN201610242209 A CN 201610242209A CN 107305181 A CN107305181 A CN 107305181A
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- 239000002904 solvent Substances 0.000 title claims abstract description 71
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000035515 penetration Effects 0.000 title claims abstract description 29
- 210000003491 skin Anatomy 0.000 claims abstract description 20
- 210000002510 keratinocyte Anatomy 0.000 claims abstract description 14
- 230000008859 change Effects 0.000 claims abstract description 8
- 229910017435 S2 In Inorganic materials 0.000 claims 1
- 238000011160 research Methods 0.000 abstract description 12
- 239000010408 film Substances 0.000 description 10
- 238000001764 infiltration Methods 0.000 description 8
- 230000008595 infiltration Effects 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 5
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000012466 permeate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
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- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Image Input (AREA)
Abstract
The present invention relates to a kind of method for studying percutaneous dosing solvent penetration, belong to percutaneous dosing studying technological domain.Comprise the following steps：S1：Human body skin is replaced using the film for being structurally and functionally similar to human skin keratinocyte's layer；S2：The film is fixed on to Fingerprint Sensor surface, picture of the different solvents in different times of penetration is gathered with the Fingerprint sensor based on electric capacity；S3：Grey level enhancement is carried out to the skin image in the case of the human body different in moisture content collected using histogram equalization；S4：To the picture of the different time permeated by pretreated different solvents, with gray level co-occurrence matrixes algorithm, the energy of image, contrast, the change of entropy and correlative character parameter are calculated；S5：Set up the characteristic parameter of gray level co-occurrence matrixes and the relation of solvent penetration speed.The present invention gives good Technical Reference to the penetration study of different solvents, and very strong technical support is also provided to percutaneous dosing research field.
Description
Technical field
The invention belongs to percutaneous dosing studying technological domain, percutaneous dosing solvent penetration field is particularly quantitatively analyzed and measures,
It is related to a kind of method for studying percutaneous dosing solvent penetration.
Background technology
Human drug absorption depends on three kinds of approach, i.e. alimentary canal, mucous membrane and skin.Wherein new medicine-feeding technology：Through
Skin administration is nearest study hotspot.During current present Research, the transdermal flux of medicine, maximum resistance
Cuticula from skin.Therefore find a kind of effective research method, studied by the research meanses of scientific and precise percutaneously to
Medicine is highly important in the diffusion of keratoderma during medicine.
Conventional research method mainly has two kinds at present：The first, the skin with the animal similar in appearance to human skin keratinocyte's layer comes
Instead of by the use of different solvents, then by pertinent instruments, for example：Corneometer and Skicon analyzes solvent
Infiltration, this method although operate relative to directly on human body skin with solvent analysis will safety and simple, still
Replace simply setting up a kind of similitude eventually with the skin of animal, human body skin is specifically acted on solvent still can have differences,
In addition, the specific design of measuring instrument is also the research for human skin keratinocyte's layer, thus the data drawn to after related
Continuous analysis judges to bring the possibility of error；The method of second of research is the skin that solvent is directly acted on to human body, is then passed through
Pertinent instruments mentioned above, to analyze the infiltration of solvent, although this method on human body with solvent because directly carry out
Analysis, reduces issuable error, but solvent directly acts on human body, can there is insecurity, and may to skin
The nocuity of presence, in addition, the commonplace measuring instrument used at present, for example：Corneometer and Skicon is right
The com-parison and analysis of human skin keratinocyte's layer moisture is accurate, but for the various solvents containing differing dielectric constant, or exist
Certain error, and measurement data can only be provided, the picture of situation is permeated in different time without solvent.
The content of the invention
In view of this, it is an object of the invention to provide a kind of method for studying percutaneous dosing solvent penetration, this method is used first
That medically generally uses at present is proximate to the film of human skin keratinocyte's layer to carry out the experiment of solvent penetration, this medical thin
Film is some higher than the similarity of general animal skin, and relative to directly by solvent action in human body, in security and nothing
There is clear superiority in traumatic aspect, although can have a certain error with real human body skin ratio, but survey tool of the present invention
That choose is the Fingerprint sensor based on electric capacity, compared to the Corneometer and Skicon generally used at present,
Analyses of the Fingerprint sensor not only to human skin keratinocyte's layer moisture is very accurate, and to containing different dielectric
The various solvents of constant are also very sensitive, and two kinds of instruments relatively mentioned above, accuracy is greatly improved, meanwhile, Fingerprint
Sensor can not only provide accurate data, but also can provide the picture that solvent permeates situation in different time, also to this
Research provides very intuitively scientific basis, meanwhile, the present invention also applies to gray level co-occurrence matrixes algorithm the difference collected
The picture of the different time of solvent penetration, have found the method for judging solvent penetration speed speed.
To reach above-mentioned purpose, the present invention provides following technical scheme：
A kind of method for studying percutaneous dosing solvent penetration, this method comprises the following steps：
S1：Human body skin is replaced using the film for being structurally and functionally similar to human skin keratinocyte's layer；
S2：The film is fixed on to Fingerprint Sensor surface, with the Fingerprint sensor based on electric capacity
To gather picture of the different solvents in different times of penetration；
S3：The image collected is pre-processed；
S4：To the picture of the different time permeated by pretreated different solvents, with gray level co-occurrence matrixes algorithm, calculate
The energy of image, contrast, the change of entropy and correlative character parameter；
S5：Set up the characteristic parameter of gray level co-occurrence matrixes and the relation of solvent penetration speed.
Further, in step s3, using histogram equalization come to the human body collected with Fingerprint Sensor not
Grey level enhancement is carried out with the skin image in the case of moisture, and then improves the contrast and definition of image.
Further, in step s 2, the film for being structurally and functionally similar to human skin keratinocyte's layer is fixed on Fingerprint
One hollow cover, is then fixed on above film by Sensor surface, and the purpose for placing cover is solvent is not flowed away,
And different solvents can be allowed to be analyzed in the case of equivalent.
The beneficial effects of the present invention are：The present invention exists with the Fingerprint sensor based on electric capacity to gather different solvents
The picture of different times of penetration, this method simple and fast is fool proof with non-invasive, can not only provide accurate number
According to, but also can provide solvent different time permeate situation picture, also to this research provide very intuitively science according to
According to, meanwhile, the present invention also applies to gray level co-occurrence matrixes algorithm in the picture of the different time of the different solvents infiltration collected,
By calculating the energy of image, contrast, the change of the characteristic parameter such as entropy and correlation establishes the feature of gray level co-occurrence matrixes
The relation of parameter and solvent penetration speed, gives good Technical Reference to the penetration study of different solvents, percutaneous dosing is ground
Study carefully field and also provide very strong technical support.
Brief description of the drawings
In order that the purpose of the present invention, technical scheme and beneficial effect are clearer, the present invention provides drawings described below and illustrated：
Fig. 1 is the schematic flow sheet of the method for the invention；
Fig. 2 is four kinds of different solvents in embodiment in six exploit graphs not in the same time；
Four characteristic vector curves that Fig. 3 is not extracted with gray level co-occurrence matrixes in the same time for four kinds of different solvents in embodiment at six
Figure:(a) energy, (b) entropy, (c) contrast, (d) correlation.
Embodiment
Below in conjunction with accompanying drawing, the preferred embodiments of the present invention are described in detail.
Fig. 1 is the schematic flow sheet of the method for the invention, as illustrated, the method that the present invention is provided specifically includes following steps：
S1：Human body skin is replaced using the film for being structurally and functionally similar to human skin keratinocyte's layer；S2：The film is fixed on
Fingerprint Sensor surface, different solvents are gathered in difference with the Fingerprint sensor based on electric capacity
The picture of time of penetration；S3：Using histogram equalization come to the human body different in moisture collected with Fingerprint Sensor
Skin image in the case of content carries out grey level enhancement；S4：To the figure of the different time permeated by pretreated different solvents
Piece, with gray level co-occurrence matrixes algorithm, calculates the energy of image, contrast, the change of entropy and correlative character parameter；S5：
Set up the characteristic parameter of gray level co-occurrence matrixes and the relation of solvent penetration speed.
The method of the present invention is described in detail below by specific embodiment.
The present invention comes gathered data and picture using Fingerprint Sensor.Fingerprint Sensor possess 256 × 300
Individual picture element matrix, every spatial resolution of each pixel is 50 microns.Its region of measurement range altogether is 12.8 × 15 microns.
Each pixel is inherently a capacitive sensing device.Capacitance sensor mainly generates the capacitance image of a skin surface,
In per piece image, each pixel can be represented by 0-255 8 gray values, its survey for all measurements
The amount duration is all limited in 5s, compared to the Corneometer and Skicon, Fingerprint generally used at present
Analyses of the sensor not only to human skin keratinocyte's layer moisture is very accurate, and to various molten containing differing dielectric constant
Agent is also very sensitive, and two kinds of instruments relatively mentioned above, accuracy is greatly improved, meanwhile, Fingerprint sensor are not
Accurate data can be only provided, but also the picture that solvent permeates situation in different time can be provided, also carried to this research
Very intuitively scientific basis is supplied.
In the present embodiment, the present invention using four kinds of the most frequently used solvents as test, i.e. PG, water, heptanol and ethanol,
They are as shown in the table respectively containing four kinds of different dielectric constants：
1 four kinds of solvent dielectric constants of table
| Solvent | Dielectric constant |
| Water | 80 |
| Ethanol | 24.55 |
| Hoptannol | 11.75 |
| PG | 32.1 |
The detailed process of test is first to be fixed on a piece of film for being structurally and functionally similar to human skin keratinocyte's layer
The hollow cover of one hexagon, is then fixed on above film by Fingerprint Sensor surface, places the mesh of cover
Be solvent is not flowed away, and four kinds of different solvents can be allowed to be analyzed in the case of equivalent, will be covered with solvent
After son is full of, measurement starts, and the time of measurement continues 1000s, and every kind of solvent is all measured using identical method, most
Whole result have chosen 80s, 200s, 400s, 600s, 800s, 1000s this six can reflect infiltration situation it is typical when
Between section analyzed, and the electric capacity gray level image at corresponding time point is collected using Fingerprint Senor, such as Fig. 2 institutes
Show, these pictures clearly reflect infiltration situation of the different solvents in different time.
Picture processing：
The present invention carries out ash using histogram equalization to the electric capacity gray level image collected with Fingerprint Sensor first
Degree enhancing, and then improve its contrast and definition.Histogram equalization is turned to a kind of method of basic setting contrast,
Often it is used in present research.General profit increases the local contrast of correspondence image in this way, particularly in figure
As interior useful data contrast closely in the case of.By such a form, brightness on the histogram just has extraordinary
Distribution.Realize by this method strengthens local contrast on the premise of overall contrast is not influenceed, and passes through
Brightness, which is adjusted, just can reach same purpose.The core content of histogram equalization processing is the gray scale original image
Histogram replaces with being uniformly distributed under whole tonal ranges from the somewhere gray scale interval of relative aggregation.Its specific implementation
It is the mode for taking image Nonlinear extension, so that by the sub-distribution again of its pixel value, the particular number of pixel will not be with ash
Degree changes and changed.The proposition of histogram equalization can for the image for becoming homogenization distribution to the histogram set the goal is provided
Energy.
Then, gray level co-occurrence matrixes algorithm process picture is utilized.Fig. 3 is that four kinds of different solvents are not common with gray scale in the same time at six
The curve map for four characteristic vectors that matrix is extracted to it is given birth to, four characteristic vectors are respectively：Energy, entropy, contrast and phase
Guan Xing.As can be seen from Figure 3 the heptanol and PG energy eigenvalue curve trend that changes with time is in slowly to decline
State, while the speed of infiltration is very slow it can be seen that both solvents change with time, therefore can be by energy and solvent
Seepage velocity set up contact, this hypothesis also obtained together in other two kinds of solvents water and etohanol variation tendency
The checking of sample.The infiltration for seeing water and eholanol that can be will be apparent that is completely rapid, the initial period started in experiment
That is infiltration is begun at the time of 200s, during afterwards, the state that tends towards stability is permeated.Simultaneously, it can be seen that both
The corresponding energy eigenvalue curve of solvent has apparent decline at the time of about 200s, then as the change curve of time
Tend to be steady, again may be by observation and obtain two other characteristic value entropy and correlation, can equally set up characteristic value and solvent
The contact of speed is permeated, and the result of contrast is less desirable.
In summary, the present invention is proximate to the film of human skin keratinocyte layer and entered using what is medically generally used at present first
, there is clear superiority in the experiment of row solvent penetration, in terms of security and non-invasive with the Fingerprint based on electric capacity
Sensor gathers picture of the different solvents in different times of penetration, and this method simple and fast is fool proof with non-invasive,
Accurate data can not only be provided, but also the picture that solvent permeates situation in different time can be provided, also studied to this
There is provided very intuitively scientific basis, meanwhile, the present invention also oozes the different solvents that gray level co-occurrence matrixes algorithm applies to collect
The picture of saturating different time, by calculating the energy of image, contrast, the change of the characteristic parameter such as entropy and correlation is set up
The characteristic parameter of gray level co-occurrence matrixes and the relation of solvent penetration speed, to the penetration study of different solvents give good skill
Art is referred to, and very strong technical support is also provided to percutaneous dosing research field.
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although by above-mentioned
The present invention is described in detail for preferred embodiment, it is to be understood by those skilled in the art that can in form and
Various changes are made in details to it, without departing from claims of the present invention limited range.
Claims (3)
1. a kind of method for studying percutaneous dosing solvent penetration, it is characterised in that：This method comprises the following steps：
S1：Human body skin is replaced using the film for being structurally and functionally similar to human skin keratinocyte's layer；
S2：The film is fixed on to Fingerprint Sensor surface, with the Fingerprint sensor based on electric capacity
To gather picture of the different solvents in different times of penetration；
S3：The image collected is pre-processed；
S4：To the picture of the different time permeated by pretreated different solvents, with gray level co-occurrence matrixes algorithm, calculate
The energy of image, contrast, the change of entropy and correlative character parameter；
S5：Set up the characteristic parameter of gray level co-occurrence matrixes and the relation of solvent penetration speed.
2. a kind of method for studying percutaneous dosing solvent penetration according to claim 1, it is characterised in that：In step S3
In, using histogram equalization come to the skin in the case of the human body different in moisture content collected with Fingerprint Sensor
Image carries out grey level enhancement, and then improves the contrast and definition of image.
3. a kind of method for studying percutaneous dosing solvent penetration according to claim 1, it is characterised in that：In step S2
In, the film for being structurally and functionally similar to human skin keratinocyte's layer is fixed on to Fingerprint Sensor surface, then will
One hollow cover is fixed on above film, and the purpose for placing cover is solvent is not flowed away, and can allow different solvents
Analyzed in the case of equivalent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610242209.8A CN107305181A (en) | 2016-04-18 | 2016-04-18 | A kind of method for studying percutaneous dosing solvent penetration |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610242209.8A CN107305181A (en) | 2016-04-18 | 2016-04-18 | A kind of method for studying percutaneous dosing solvent penetration |
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| CN107305181A true CN107305181A (en) | 2017-10-31 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1595141A (en) * | 2004-06-18 | 2005-03-16 | 中国药科大学 | Process for detecting active ingredients of traditional Chinese medicine |
| CN101341389A (en) * | 2005-12-20 | 2009-01-07 | 底格里蒙公司 | Method and device for testing the integrity of filtration membranes |
| CN102015025A (en) * | 2008-02-15 | 2011-04-13 | 压电共振概念有限公司 | Transdermal micro-patch |
| CN102831424A (en) * | 2012-07-31 | 2012-12-19 | 长春迪瑞医疗科技股份有限公司 | Method for extracting visible component by microscope system |
-
2016
- 2016-04-18 CN CN201610242209.8A patent/CN107305181A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1595141A (en) * | 2004-06-18 | 2005-03-16 | 中国药科大学 | Process for detecting active ingredients of traditional Chinese medicine |
| CN101341389A (en) * | 2005-12-20 | 2009-01-07 | 底格里蒙公司 | Method and device for testing the integrity of filtration membranes |
| CN102015025A (en) * | 2008-02-15 | 2011-04-13 | 压电共振概念有限公司 | Transdermal micro-patch |
| CN102831424A (en) * | 2012-07-31 | 2012-12-19 | 长春迪瑞医疗科技股份有限公司 | Method for extracting visible component by microscope system |
Non-Patent Citations (2)
| Title |
|---|
| 杨晓旗等: "高吸水卫生材料动态吸水特性的测试方法", 《浙江理工大学学报》 * |
| 许舒斐等: "基于灰度共生矩阵的人体皮肤纹理分析", 《激光生物学报》 * |
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