CN107929317A - Transdermal absorption liquid and its preparation method and application - Google Patents

Transdermal absorption liquid and its preparation method and application Download PDF

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Publication number
CN107929317A
CN107929317A CN201711212353.8A CN201711212353A CN107929317A CN 107929317 A CN107929317 A CN 107929317A CN 201711212353 A CN201711212353 A CN 201711212353A CN 107929317 A CN107929317 A CN 107929317A
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transdermal absorption
water
absorption liquid
concentration
strontium
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王兴南
张恩甫
覃文新
顾帝水
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Shanghai Reoxy Enterprise Development Co Ltd
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Shanghai Reoxy Enterprise Development Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin

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  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a kind of Transdermal absorption liquid and its preparation method and application, the Transdermal absorption liquid is formed including following component:Strontium concentration is 0.2 10mg/L, and selenium concentration is 0.005 0.02mg/L, and the counting content of oxygen atom is 2.82*1020‑7.52*1020A/L, surplus are water.The formula of the present invention is natural, it is safe to the human body harmless, it is without side-effects, the polymorphic oxygen of high concentration, selenium and strontium, it is used for the aqueous formulation of Transdermal absorption at a certain temperature, tumour growth can effectively be suppressed, available for the side effect in adjuvant therapy treatment and remissive treatment, be conducive to accelerate the physical recovery after treatment.

Description

Transdermal absorption liquid and its preparation method and application
Technical field
The present invention relates to the technical field for suppressing growth of tumour cell and medicine synergistic treatment, is particularly suitable for suppressing tumour Transdermal absorption liquid of cell growth and its preparation method and application.
Background technology
With environmental pollution, the deterioration of environment for human survival, more and more diseases corrode the body of people.Tumour is Threaten a kind of persistent ailment of human life and health, main at present treatment means such as antitumor drug combined chemotherapy, radiotherapy and operation Treatment etc. effect it is indubitable, but there are it is certain the defects of.While killing tumor cell, to surrounding normal cell and Tissue causes to damage also indiscriminately, and especially chemotherapy and radiation can also produce the toxic side effects such as bone marrow suppression.Therefore, do not have The suppression of toxic side effect or collaboration means are the development trends of current cancer therapies.
Germany scientist Otto doctors Warburg in 1931 obtain the Nobel Prize in the cause for finding cancer, and Nineteen forty-four wins a prize again.It is described as in it wins a prize conclusion:Although cancer is a very complicated disease, have with many factors Close, but the normal oxygen breathing that it has an important cause to be exactly human body cell is substituted by anaerobic respiration, is exactly to work as cell In oxygen content it is subnormal 65% when cell be forced to be switched to a kind of physiology course-glycolysis of poor ATP energy, Cell is difficult to recover normal oxidation energy production system.People used ozone gas to fumigate and breathe anion in decades Air cancer is suppressed or is treated, largely also demonstrate that oxygen to the important of human body diseases rehabilitation in health care and therapy field Property, but these methods are all without obvious tumor inhibition effect.Cancer is used as by lung's oxygen uptake and the oxygen supply of high pressure human body oxygen cabin The rehabilitation supplementary means of patient is also more and more paid close attention to by researcher and clinician.
In September, 2016, the William G.Kaelin of Harvard Medical School's Da Na-Fa Bai Cancer Institutes, Jr., Oxford are big Learn the Peter J.Ratcliffe of the Mark Lewis-Francis Crick research institute and Gregg of John Hopkins medical college L.Semenza obtains the prize of U.S. Lars gram basic medical research, they are to human body and most animals cells perception and adapt to oxygen The discovery of gas change mechanism, they study by cultivating mankind mastopathy cell and mouse mastopathy cell, find whole Close to exist between element connection kinases and cancer stem cell and associate.
In conventional oncotherapy, chemicotherapy is the common method in Multimodality Therapy of Malignant Tumors, for kinds of tumors Treatment, but Radiotherapy chemotherapy play anticancer, cancer suppressing action while a series of caused toxicities also can not be ignored, put Ray and chemotherapeutics also have considerable degree of damage to human normal cell such as bone marrow cell, gastrointestinal tract mucous cell etc..Face The normal cell of a variety of toxicities often occurred during bed chemicotherapy, radiation or drug induced injury is required for during reparation Substantial amounts of oxygen is supported to repair.Immune or oxygen pair of numerous researchers' research oxygen in body is associated with tumour, is traditionally had The supplement for only carrying out human body by hyperbaric oxygen chamber or oxygen uptake to human body oxygen supply of effect.
Micro- such as selenium, strontium in water are the necessary trace elements of human body.Selenium can promote lymphocyte propagation and The synthesis of antibody, immunoglobulin, improves the immunity of the human body, and has to kinds cancers such as colon cancer, cutaneum carcinoma, liver cancer and suppress Effect;Human body can promote cell repair and body metabolism to the intake of suitable strontium, improve body immunity.
Selenium and strontium are that human body can not synthesize, it is necessary to the trace element obtained from the external world in itself.Traditionally human body is to selenium, strontium Supplement mainly by food or drug oral rich in selenium, strontium, absorbs intake via intestines and stomach and obtains.
With conventional oral take in compared with, by way of Transdermal absorption, high concentration oxygen, selenium and strontium can directly by skin into Enter region of interest, can also be had an effect by blood circulation to whole body, action time is shorter.
For numerous science arguments, research show growth and immune deficiency and the anaerobic environment in body of tumour with And the micro- serious loss such as selenium, strontium is closely related.Lack effective means at present by supplementing high concentration oxygen, selenium and strontium, Improve internal body environment, and cooperate with existing medical therapy to realize and tumour is significantly inhibited.
At present, a kind of safety Transdermal absorption liquid without side-effects and its preparation method and application is lacked.
The content of the invention
Regarding the issue above, the present invention provides a kind of safety Transdermal absorption liquid without side-effects and its preparation side Method and application.
To realize above-mentioned technical purpose, the present invention provides following technical solution:A kind of Transdermal absorption liquid, the transdermal suction Liquid is received to form including following component:
Strontium concentration is 0.2-10mg/L,
Selenium concentration is 0.005-0.02mg/L,
The counting content of oxygen atom is 2.82*1020-7.52*1020A/L,
Surplus is water.
It is used to prepare in the water of inventive formulation also containing other as Na+, K+, Ca+ etc. meet normal drinking water standard Mineral composition;And also containing the other natural or chemical compositions beneficial to human body for being capable of Transdermal absorption.Under normal temperature and pressure Dissolved oxygen amount in light water is generally 5-10mg/L, and the counting content of oxygen atom is 0.94*1020-1.88*1020A/L, room temperature Selenium concentration under normal pressure in light water is 0.001-0.003mg/L, and strontium concentration is 0.1-0.3mg/L.
Dissolved oxygen amount after being placed 50 minutes under the formula aqueous solution normal temperature and pressure conditions of the present invention is 15-40mg/L, and oxygen is former The counting content of son is 2.82*1020-7.52*1020A/L.The oxygen that the counting content of the oxygen atom is added in being prepared for formula Atomic quantity, not comprising original oxygen atom quantity, content 2.82*10 in water20-7.52*1020A/L represent every liter it is water-soluble The total quantity that oxygen atom is added in liquid is 2.82*1020-7.52*1020It is a.
Further, the existing forms of the oxygen are O-、O、O2 -Or O2;The area of the Transdermal absorption liquid Transdermal absorption accounts for The 30-100% of body surface product, can carry out Transdermal absorption by way of body part or all immersion, shower.
Further, when carrying out Transdermal absorption, the temperature of Transdermal absorption liquid is 10 DEG C -45 DEG C, and the selenium concentration is 0.01- 0.015mg/L;The strontium concentration is 5.5-8.5mg/L.
Further, the counting content of oxygen atom described in the Transdermal absorption liquid is 5.64*1020-7.52*1020A/ L, the temperature of the Transdermal absorption liquid is 30 DEG C -40 DEG C.When aqueous temperature is 30 DEG C -40 DEG C, during Transdermal absorption to oxygen, selenium and The absorption efficiency of strontium is all higher.
A kind of preparation method of Transdermal absorption liquid of the present invention, includes the following steps:
(1) water that water temperature is 10-45 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through in water The quantitative delivery apparatus being arranged in water inlet pipe road is adjusted respectively;
(2) oxygenous, negative oxygen ion gas mixed gas is respectively enterd by booster transportation apparatus with the water of conveying In mixing arrangement, exported after carrying out mixed dissolution under pressure state, Transdermal absorption liquid is made.
Further, in step (1) and (2), the mixing arrangement includes at least static mixing element or dynamic mixes The combination of one or both of element.
Further, in step (2), the pressure is not less than 1bar, the selenium and strontium in the Transdermal absorption liquid it is dense Degree, can supplement adjusting by way of being added into water.
Further, in step (1), the mixing arrangement is dynamic hybrid element, and the dynamic hybrid element is One dynamic mixers, the dynamic mixers include stator, rotor and housing, and the stator and the rotor are arranged on described In housing, one end of the housing is provided with the input terminal for importing the soluble gas and the water, the housing The other end is provided with the output terminal for exporting air-water mixture, and the output terminal connection is conducted on the mixed pipe line.
Application of the Transdermal absorption liquid of the present invention in growth of tumour cell and medicine collaboration is suppressed.
The tumour cell is colon cancer tumours cell.
Beneficial effects of the present invention:
The formula of the present invention is natural, safe to the human body harmless, without side-effects, the polymorphic oxygen of high concentration, selenium and strontium, certain At a temperature of be used for Transdermal absorption aqueous formulation, can effectively suppress tumour growth, available for adjuvant therapy treat and alleviate Side effect in treatment, is conducive to accelerate the physical recovery after treatment.
Compared with prior art, the invention has the advantages that:
(1) concentration of the concentration range containing selenium and strontium in Transdermal absorption formula of liquid, selenium and strontium can be by into aqueous solution The mode of addition is adjusted.Also containing the natural or chemical composition beneficial to human body for being capable of Transdermal absorption in water.
(2) a kind of aqueous formulation containing the polymorphic oxygen of high concentration, selenium and strontium of the invention, is used for saturating at a certain temperature Skin absorb mode, can effectively suppress tumour growth, available for adjuvant therapy treatment and remissive treatment in side effect, favorably Physical recovery after accelerating to treat, realizes that the general level of the health of lifting human body especially suppresses the target of tumour growth.
(3) Transdermal absorption liquid of the invention also has increase erythrocyte oxygen carrying content in other application research, improves skin Skin elasticity and other effects.
Brief description of the drawings
Fig. 1-a are the figure that formula aqueous solution water-bath of the present invention containing high concentration oxygen influences growth of transplanted human curve and knurl weight Spectrum.
Fig. 1-b are the figure that formula aqueous solution water-bath of the present invention containing high concentration oxygen influences growth of transplanted human curve and knurl weight Spectrum.
Fig. 2 is the different formulations water-bath of the invention containing high concentration oxygen, selenium, strontium to CT-26 subcutaneous transplantation knurl growth curves The collection of illustrative plates of influence.
Embodiment
It is described further below with reference to the technique effect of design of the attached drawing to the present invention, concrete structure and generation, with It is fully understood from the purpose of the present invention, feature and effect.
Embodiment 1
A kind of Transdermal absorption liquid of the present invention, the Transdermal absorption liquid are formed including following component:
Strontium concentration is 10mg/L,
Selenium concentration is 0.005mg/L,
The counting content of oxygen atom is 2.82*1020A/L,
Surplus is water.
It is used to prepare in the water of inventive formulation also containing other as Na+, K+, Ca+ etc. meet normal drinking water standard Mineral composition;And also containing the natural or chemical composition beneficial to human body for being capable of Transdermal absorption.The meter of the oxygen atom The oxygen atom quantity that number content is added in being prepared for formula, not comprising original oxygen atom quantity, content 2.82*10 in water20 The quantity that a/L represents to add oxygen atom in per aqueous solution is 2.82*1020It is a.
The existing forms of the oxygen are O-、O、O2 -Or O2;The area of the Transdermal absorption liquid Transdermal absorption accounts for body surface Long-pending 70%, when carrying out Transdermal absorption, the temperature of Transdermal absorption liquid is 45 DEG C.During using Transdermal absorption mode, transdermal area accounts for The 30% of body surface product, can carry out Transdermal absorption by way of shower.
The preparation method of the Transdermal absorption liquid of the present invention, includes the following steps:
(1) water that water temperature is 45 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through setting in water Quantitative delivery apparatus (commercially available in the prior art, only need to adjust injected volume) in water inlet pipe road is adjusted respectively;It is described Mixing arrangement is dynamic hybrid element.
The dynamic hybrid element is a dynamic mixers, and the dynamic mixers include stator, rotor and housing, institute State stator and the rotor be arranged in the housing, one end of the housing be provided with for import the soluble gas and The input terminal of the water, the other end of the housing are provided with the output terminal for exporting air-water mixture, and the output terminal connects Connect and be conducted on the mixed pipe line.
(2) oxygenous, negative oxygen ion gas mixed gas is respectively enterd by booster transportation apparatus with the water of conveying In mixing arrangement, exported after carrying out mixed dissolution under pressure state, the pressure is not less than 1bar, in the Transdermal absorption liquid Selenium and strontium concentration, adjusting can be supplemented by way of being added into water.Transdermal absorption liquid is made.
Application of the Transdermal absorption liquid of the present invention in growth of tumour cell and medicine collaboration is suppressed.
The tumour cell is colon cancer tumours cell.
The aqueous formulation of the present invention passes through Publication No. CN104174311A " bathing nanometer microbubble generator and bubble The disclosed device of bath system " is prepared, and can use dynamic hybrid element or static mixing element or two in its mixing arrangement Person combines, and the mixed pipe line being attached thereto.Water is inputted by delivery pump, is provided with water inlet pipe road selenium, strontium is determined Delivery device is measured, to carry out supplement adjusting to the concentration of selenium strontium in water.The oxydant of high concentration, such as oxygen, negative oxygen ion gas Body etc. is respectively enterd in mixing arrangement, after carrying out mixed dissolution under pressure state by booster transportation apparatus with the water of conveying Output application.The oxydant of high concentration is in aqueous with O-, O, O2 -, O2Exist Deng variform, oxygen atom counts content Calculation according to formula aqueous solution placed 50 minutes under normal temperature and pressure conditions after dissolved oxygen amount be foundation.
Selenium and strontium are the trace element beneficial to human body.Research shows, carries out Transdermal absorption when the temperature is low, the suction to oxygen Rate of producing effects is higher, and the infiltration rate of selenium and strontium compared with slow and absorption efficiency is low, when temperature is high, the infiltration rate of selenium and strontium becomes It hurry up, absorption efficiency improves, but the bad stability of oxygen in water causes absorption efficiency to reduce under high temperature.
Embodiment 2
Embodiment 2 is substantially the same manner as Example 1, difference lies in:
A kind of Transdermal absorption liquid of the present invention, the Transdermal absorption liquid are formed including following component:
Strontium concentration is 0.2mg/L,
Selenium concentration is 0.02mg/L,
The counting content of oxygen atom is 7.52*1020A/L,
Surplus is water.
It is used to prepare in the water of inventive formulation also containing other as Na+, K+, Ca+ etc. meet normal drinking water standard Mineral composition;And also containing the natural or chemical composition beneficial to human body for being capable of Transdermal absorption.
The existing forms of the oxygen are O-、O、O2 -Or O2;The area of the Transdermal absorption liquid Transdermal absorption accounts for body surface Long-pending 30%, can carry out Transdermal absorption by way of all soaking.
When carrying out Transdermal absorption, the temperature of Transdermal absorption liquid is 10 DEG C.During using Transdermal absorption mode, transdermal area accounts for flesh The 100% of body surface area, can carry out Transdermal absorption by way of body all immersion, shower.
The oxygen atom quantity that the counting content of the oxygen atom is added in being prepared for formula, it is former not comprising original oxygen in water Quantum count, content 7.52*1020The total quantity that a/L represents to add oxygen atom in per aqueous solution is 7.52*1020It is a.
The preparation method of the Transdermal absorption liquid of the present invention, includes the following steps:
(1) water that water temperature is 10 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through setting in water Quantitative delivery apparatus in water inlet pipe road is adjusted respectively;The mixing arrangement is static mixing element.
(2) oxygenous, negative oxygen ion gas mixed gas is respectively enterd by booster transportation apparatus with the water of conveying In mixing arrangement, exported after carrying out mixed dissolution under pressure state, the pressure is not less than 1bar.In the Transdermal absorption liquid Selenium and strontium concentration, adjusting can be supplemented by way of being added into water.Transdermal absorption liquid is made.
Embodiment 3
Embodiment 3 is substantially the same manner as Example 1, difference lies in:
A kind of Transdermal absorption liquid of the present invention, the Transdermal absorption liquid are formed including following component:
Strontium concentration is 8.5mg/L,
Selenium concentration is 0.015mg/L,
The counting content of oxygen atom is 6.58*1020A/L,
Surplus is water.
The area of the Transdermal absorption liquid Transdermal absorption accounts for the 100% of body surface product, when carrying out Transdermal absorption, transdermal suction The temperature for receiving liquid is 35 DEG C.
Transdermal area accounts for the 80% of body surface product, can carry out Transdermal absorption by the bathing mode of body part.
The oxygen atom quantity that the counting content of the oxygen atom is added in being prepared for formula, it is former not comprising original oxygen in water Quantum count, content 6.58*1020The total quantity that a/L represents to add oxygen atom in per aqueous solution is 6.58*1020It is a.
The preparation method of the Transdermal absorption liquid of the present invention, includes the following steps:
(1) water that water temperature is 35 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through setting in water Quantitative delivery apparatus in water inlet pipe road is adjusted respectively;The mixing arrangement is static mixing element and dynamic hybrid element Two kinds of combination.
(2) oxygenous, negative oxygen ion gas mixed gas is respectively enterd by booster transportation apparatus with the water of conveying In mixing arrangement, exported after carrying out mixed dissolution under pressure state, Transdermal absorption liquid is made.
Experiment 1
The preparation process of Transdermal absorption liquid of the present invention
The water that water temperature is 10-45 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through setting in water Quantitative delivery apparatus in water inlet pipe road is adjusted respectively;Oxygenous, negative oxygen ion gas mixed gas is passed through into supercharging Conveying device, respectively enters in mixing arrangement with the water of conveying, exports, is prepared after carrying out mixed dissolution under pressure state An aqueous solution (selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature) is formulated, is formulated the two aqueous solution (meter of oxygen atom Number content is 3.76*102035 DEG C of a/L, water temperature), (the counting content of oxygen atom is 3.76*10 to three aqueous solutions of formula20A/L, Selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature), (the counting content of oxygen atom is 6.58* to four aqueous solutions of formula 1020A/L, selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature), it is formulated five aqueous solutions (the counting content of oxygen atom For 7.52*1020A/L, selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature).
Transdermal absorption liquid of the present invention tests the inhibition of colon cancer tumours
Experiment of Zoology:Inventive formulation aqueous solution gives birth to mouse colonic cell CT-26 transplantable tumors using bathing mode Long influence
1. material and method
1.1 main material
Inventive formulation aqueous solution and preparation facilities (offer of Shanghai Lei Yang enterprise developments Co., Ltd) mouse junction cancer are thin Born of the same parents (CT-26) (offer of Shanghai institute of oncology), 4-6 week old female BAl BIc/c mouse (132), 5 FU 5 fluorouracil (5-FU) (Shanghai Xudong Hipu Medicine Co., Ltd, lot number:FA130712), DMEM culture mediums (GIBCO), hyclone (FBS) (Biowest)。
1.2 method
1.2.1 cell culture
CT-26 cell culture is in DMEM nutrient solutions (ampicillin containing 100U/mL, 100U/mL sulfuric acid containing 10%FBS Streptomysin) in, it is 90% or so to grow to cell density, is digested using 0.25% pancreatin digestive juice, digestion is terminated, with complete Full DMEM nutrient solutions piping and druming is inoculated in diameter 10cm culture dishes into Single cell suspensions, is placed in 37 DEG C, 5%CO2In incubator into Row culture, is passed on every other day.
1.2.2CT-26 subcutaneous transplantation knurl model foundation
Take the CT-26 cells in exponential phase to be digested, after terminating digestion, blown and beaten with serum-free DMED into slender Born of the same parents' suspension, carries out cell count, using cell number as 1 × 106/ aseptically injection inoculation to the right armpit of BALB/c mouse Side is subcutaneous.
1.2.3 experiment packet and administration
CT-26 is inoculated in BALB/c mouse subcutaneous the 2nd day afterwards, and mouse is randomly divided into 12 groups, and the 1st, 2,3,4 group is every group 8 Only, the 5th, 6,7,8,9,10,11,12 group is every group 7.1st group is control group, carries out common water-bath (35 DEG C of water temperature);2nd group Carry out formula one aqueous solution (selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature) water-bath;3rd group carries out formula two (the counting content of oxygen atom is 3.76*10 to aqueous solution2035 DEG C of a/L, water temperature) water-bath;4th group carries out three aqueous solution (oxygen of formula The counting content of atom is 3.76*1020A/L, selenium concentration 0.015mg/L, strontium concentration 8.5mg/L, 35 DEG C of water temperature) water-bath;1st, 2nd, it is inoculated with the 2nd day start to process from CT-26 for 3,4 groups.5th, 6,7,8,9,10,11,12 group after mouse into carrying out water-bath again after knurl And administration mixed processing, the 5th group is control group, carries out common water-bath (35 DEG C of water temperature) and injecting normal saline (NS) (0.1ml/ 10g);6th group is one aqueous solution water-bath of formula and injecting normal saline (0.1ml/10g);7th group is formula two aqueous solution water-bath With injecting normal saline (NS) (0.1ml/10g);8th group is three aqueous solution water-baths of formula and injecting normal saline (NS) (0.1ml/10g);9th group is common water-bath and injection 5-FU (30mg/kg, 0.1ml/10g);10th group is one aqueous solution of formula Water-bath and injection 5-FU (30mg/kg, 0.1ml/10g);11st group for formula two aqueous solution water-bath and injection 5-FU (30mg/kg, 0.1ml/10g);12nd group is three aqueous solution water-baths of formula and 5-FU (30mg/kg, 0.1ml/10g).
Mouse systemic is is soaked in water by water-bath mode, and only remainder portion is exposed.Carry out common water-bath and formula water Solution water-bath 2 times a day, 50 minutes every time, and injecting normal saline or 5-FU are 1 times a week.The measurement transplanting in every 3 days from the 7th day Knurl major diameter (a) and minor axis (b), calculate knurl volume (V=0.5 × ab2), terminate to test after 3 weeks (21 days), claim mouse weight and take Knurl claims knurl weight, calculate tumour inhibiting rate [IR=(control group be averaged knurl weight-experimental group be averaged knurl weight)/control group be averaged knurl weight × 100%].
2. interpretation of result
2.1 influences of the formula aqueous solution water-bath to growth of transplanted human curve and knurl weight containing high concentration oxygen
Influence such as Fig. 1-a and Fig. 1-b institute of the formula water-bath containing high concentration oxygen to CT-26 subcutaneous transplantation knurl growth curves Show, by 1 group and 3 groups of contrasts, 5 groups and 7 groups of contrasts, 9 groups and 11 groups of contrasts, show that the formula water-bath group containing high concentration oxygen is obvious Mouse subcutaneous transplanting knurl than the formula water-bath group without high concentration oxygen is slow-growing.Formula water-bath containing high concentration oxygen is to CT- The influence of 26 subcutaneous transplantation knurl mouse weights, knurl weight and tumour inhibiting rate is as shown in table 1:
Table 1
Group Classification Weight (g) Knurl weight (g) Tumour inhibiting rate (%)
1 group Control 24.31±2.16 3.24±0.35 -
3 groups Formula two 23.34±1.04 2.76±0.31 14.93
5 groups NS, control 24.8±3.23 3.63±0.62 --
7 groups It is formulated two+NS 23.06±1.9 2.41±0.22 33.58
9 groups 5-FU 25.3±1.83 3.57±0.53 1.49
11 groups It is formulated two+5-FU 23.44±2.21 2.43±0.29 32.05
As shown in table 1, the formula water-bath group containing high concentration oxygen is 3,7,11 groups, the opposite formula water-bath for being free of high concentration oxygen 1,5,9 group of mouse weight of group has declined, and knurl weight is smaller, its tumour inhibiting rate suppresses transplantable tumor life between 10%~35% Long trend is obvious.
Result above shows have in inventive formulation containing growth of the high concentration oxygen to colon cancer tumours cell and suppress to make With.
Influence of the 2.2 formula aqueous solution water-baths containing high concentration oxygen, selenium, strontium to transplantable tumor knurl weight
Influence such as table 2 institute of the formula water-bath containing selenium, strontium to CT-26 subcutaneous transplantation knurls mouse weight, knurl weight and tumour inhibiting rate Show:
Table 2
Group Classification Weight (g) Knurl weight (g) Tumour inhibiting rate (%)
1 group Control 24.31±2.16 3.24±0.35 -
2 groups Formula one 23.92±0.98 3.16±0.32 2.51
5 groups NS, control 24.8±3.23 3.63±0.62 --
6 groups It is formulated+a NS 24.53±1.88 3.52±0.37 2.94
As shown in table 2, (selenium concentration 0.015mg/L, strontium concentration are a 8.5mg/L) aqueous solution water-bath group 2,6 components are formulated Not with 1,5 group of control group it was found that mouse weight and knurl weight are in a slight decrease, tumour inhibiting rate is respectively 2.51% and 2.94%, is shown There is certain inhibitory action containing the growth of selenium and strontium to colon cancer tumours cell in inventive formulation.
Formula water-bath containing high concentration oxygen, selenium, strontium is to the shadow of CT-26 subcutaneous transplantation knurls mouse weight, knurl weight and tumour inhibiting rate Ring as shown in table 3:
Table 3
Group Classification Weight (g) Knurl weight (g) Tumour inhibiting rate (%)
1 group Control 24.31±2.16 3.24±0.35 -
3 groups Formula two 23.34±1.04 2.76±0.31 14.93
4 groups Formula three 22.87±1.27 2.54±0.19 21.76
5 groups NS, control 24.8±3.23 3.63±0.62 --
7 groups It is formulated two+NS 23.06±1.9 2.41±0.22 33.58
8 groups It is formulated three+NS 22.85±1.86 2.23±0.39 38.46
9 groups 5-FU 25.3±1.83 3.57±0.53 1.49
11 groups It is formulated two+5-FU 23.44±2.21 2.43±0.29 32.05
12 groups It is formulated three+5-FU 23.2±1.62 2.24±0.34 38.15
As shown in table 3, using formula two, (the counting content of oxygen atom is 3.76*1020A/L) water-bath group 3,7,11 (the counting content of oxygen atom is 3.76*10 for group and use formula three20A/L, selenium concentration 0.015mg/L, strontium concentration are 8.5mg/ L water-bath group 4), 8,12 groups compare show respectively, relative to formula two, using the water-bath group of formula three to CT-26 subcutaneous transplantations Knurl mouse weight has declined, and knurl weight is reduced, and tumour inhibiting rate improves.
The above results show, relative to formula one and formula two, the growth of three pairs of colon cancer tumours cells of formula has more Obvious inhibitory action, inventive formulation middle and high concentration oxygen have association with trace elements of selenium, suppression of the strontium to growth of tumour cell Same-action.
Influence of the 2.2 optimization of C/C composites aqueous solution water-baths containing high concentration oxygen, selenium, strontium to growth of transplanted human curve and knurl weight
For the Optimal Experimental of formula three:CT-26 is inoculated in BALB/c mouse subcutaneous the 2nd day afterwards, and mouse is randomly divided into 2 Group, is respectively the 13rd, 14 group, every group 7, the 13rd group carries out formula four (the counting content of oxygen atom is 6.58*1020A/L, selenium Concentration 0.015mg/L, strontium concentration are 8.5mg/L, 35 DEG C of water temperature) aqueous solution water-bath;3rd group carries out the (meter of oxygen atom of formula five Number content is 7.52*1020A/L, selenium concentration 0.015mg/L, strontium concentration are 8.5mg/L, 35 DEG C of water temperature) aqueous solution water-bath.It is other Implement according to method described in above-mentioned 1.2.3 steps.
Different formulations water-bath containing high concentration oxygen, selenium, strontium is to influence such as Fig. 2 institutes of CT-26 subcutaneous transplantation knurl growth curves Show, relative to formula three, the mouse subcutaneous transplanting knurl growth of the aqueous solution water-bath group of formula four and formula five is slower, and both It is not much different.Different formulations water-bath containing high concentration oxygen, selenium, strontium is to CT-26 subcutaneous transplantation knurls mouse weight, knurl weight and tumour inhibiting rate Influence it is as shown in table 4.
Table 4
Group Classification Weight (g) Knurl weight (g) Tumour inhibiting rate (%)
1 group Control 24.31±2.16 3.24±0.35 -
4 groups Formula three 22.87±1.27 2.54±0.19 21.76
13 groups Formula four 21.06±1.46 1.92±0.23 40.87
14 groups Formula five 20.69±1.22 1.9±0.18 41.36
As shown in table 4, compared with formula three, the CT-26 subcutaneous transplantation knurls of the aqueous solution water-bath group of formula four and formula five Mouse weight has declined, and knurl weight is reduced, and tumour inhibiting rate significantly improves, and tumour inhibiting rate is close.
The above results show that the growth of five pairs of colon cancer tumours cells of formula four and formula has significant inhibitory action, And both are not much different, it is contemplated that the other factors such as manufacturing cost, formula four is optimization formula.
Preferred embodiment of the invention described in detail above.It should be appreciated that those of ordinary skill in the art without Need creative work to conceive according to the present invention and make many modifications and variations.Therefore, all technologies in the art Personnel are available by logical analysis, reasoning, or a limited experiment on the basis of existing technology under this invention's idea Technical solution, all should be in the protection domain being defined in the patent claims.

Claims (10)

  1. A kind of 1. Transdermal absorption liquid, it is characterised in that:The Transdermal absorption liquid is formed including following component:
    Strontium concentration is 0.2-10mg/L,
    Selenium concentration is 0.005-0.02mg/L,
    The counting content of oxygen atom is 2.82*1020-7.52*1020A/L,
    Surplus is water.
  2. 2. Transdermal absorption liquid according to claim 1, it is characterised in that:The existing forms of the oxygen are O-、O、O2 -Or O2; The area of the Transdermal absorption liquid Transdermal absorption accounts for the 30-100% of body surface product, can be soaked by body part or all, The mode of shower carries out Transdermal absorption.
  3. 3. Transdermal absorption liquid according to claim 1, it is characterised in that:The temperature of the Transdermal absorption liquid is 10 DEG C -45 DEG C, the selenium concentration is 0.01-0.015mg/L;The strontium concentration is 5.5-8.5mg/L.
  4. 4. Transdermal absorption liquid according to claim 1, it is characterised in that:The counting content of the oxygen atom is 5.64* 1020-7.52*1020A/L, the temperature of the Transdermal absorption liquid is 30 DEG C -40 DEG C.
  5. 5. the preparation method of Transdermal absorption liquid described in claim 1, it is characterised in that include the following steps:
    (1) water that water temperature is 10-45 DEG C is input in mixing arrangement by delivery pump, selenium, the concentration of strontium pass through setting in water Quantitative delivery apparatus in water inlet pipe road is adjusted respectively;
    (2) oxygenous, negative oxygen ion gas mixed gas is respectively enterd with the water of conveying and mixed by booster transportation apparatus In device, exported after carrying out mixed dissolution under pressure state, Transdermal absorption liquid is made.
  6. 6. the preparation method of Transdermal absorption liquid according to claim 5, it is characterised in that:In step (1) and (2), institute State combination of the mixing arrangement for one or both of static mixing element or dynamic hybrid element.
  7. 7. the preparation method of Transdermal absorption liquid according to claim 5, it is characterised in that:In step (2), the pressure Not less than 1bar, the concentration of selenium and strontium in the Transdermal absorption liquid, can supplement adjusting by way of being added into water.
  8. 8. the preparation method of Transdermal absorption liquid according to claim 6, it is characterised in that:In step (1), the dynamic Hybrid element is a dynamic mixers, and the dynamic mixers include stator, rotor and housing, the stator and the rotor It is arranged in the housing, one end of the housing is provided with the input terminal for importing the soluble gas and the water, The other end of the housing is provided with the output terminal for exporting air-water mixture, and the output terminal connection is conducted to the mixing On pipeline.
  9. 9. application of claim 1 to the 8 any one of them Transdermal absorption liquid in growth of tumour cell and medicine collaboration is suppressed.
  10. 10. application according to claim 9, the tumour cell is colon cancer tumours cell.
CN201711212353.8A 2017-11-28 2017-11-28 Transdermal absorption liquid and its preparation method and application Pending CN107929317A (en)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
CN1169471A (en) * 1996-06-28 1998-01-07 牛西午 Selenium-strontium-rich black-buckwheat health-care vinegar and preparation method thereof
WO2005032480A2 (en) * 2003-10-03 2005-04-14 Judith Boston Methods, compositions,, apparatuses containing tetrameric oxygen
CN104174311A (en) * 2014-08-15 2014-12-03 王兴南 Nano micro bubble generation device for bathing and bathing system
CN106669024A (en) * 2015-11-11 2017-05-17 吴健忠 New method for preventing and treating cancer

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樊慧婷,等: "康艾注射液调节荷瘤机体免疫功能的研究", 《中国新药杂志》 *
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Application publication date: 20180420