CN108653262A - Ketoprofen external used medicine and its preparation method and application - Google Patents
Ketoprofen external used medicine and its preparation method and application Download PDFInfo
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The present invention provides a kind of Ketoprofen external used medicines and its preparation method and application, are related to technical field of medicine, Ketoprofen external used medicine provided by the invention, and component includes Ketoprofen, cosolvent, skin penetration enhancer and stabilizer.Pass through the coordinated between each specific components and proportioning, make Ketoprofen external used medicine provided by the invention that can reduce the degree of allodynia, shorten the time of pain and rehabilitation, avoid the generation of irreversible damage, to substantially increase the effect for the treatment of, and have both easy to use, lower-cost advantage.Preparation method provided by the invention can obtain the good Ketoprofen external used medicine of analgesic effect by specific component addition sequence and mixing, dissolving.External application analgesic drug provided by the invention, including analgesic provided by the invention combination, can significantly reduce ANIMAL PAIN, and play the role of eliminating swelling, improve animal welfare, accelerate animal rehabilitation, increase economic efficiency.
Description
Technical field
The present invention relates to technical field of medicine, more particularly, to a kind of Ketoprofen external used medicine and preparation method thereof and
Using.
Background technology
With economic rapid development, animal-breeding intensive degree is higher and higher, and Animal diseases are also more next more, increasingly
It is complicated.Especially infectious diseases.Such as various diseases of pneumonia, enteritis, mammitis, hysteritis, finally embody in animals
For symptoms such as inflammation, fever, pain.
Ketoprofen belongs to a kind of efficient non-steroidal anti-inflammatory drug (NSAIDs), have the function of it is anti-inflammatory, analgesia, it is antipyretic,
It is scorching to inhibit to cause mainly by the activity of reversible inhibition cyclooxygenase (COXs), proinflammatory peptide or lipoxidase (LOXs)
Property substance prostaglandin (PGs), leukotriene (LTs) and thromboxane (TXs) biosynthesis, so that bradykinin release is reduced, in turn
Play its good anti-inflammatory, analgesia and refrigeration function.Clinically main application for the treatment of rheumatic or rheumatoid joint are cured in people
Other related inflammatory diseases such as inflammation, ankylosing spondylitis, osteoarthritis；And wound, postoperative pain, acute renal colic, intestines twist
Bitterly, pain caused by gout breaking-out etc..Main application for the treatment of milk cow, horse, pig mammitis of animal, mammary gland water on veterinary clinic
The inflammatory diseases and intestinal colic, skeletal muscle wound etc. such as swollen, pneumonia, arthritis.
In recent years, animal welfare is concerned, and the research for having some mechanisms to be absorbed in ANIMAL PAIN, wherein also include by
The pain caused by disease and pain are influenced caused by production performance.For example the treatment of pet postoperative pain, horse racing intestines twist
Bitterly, the treatment etc. of skeletal muscle trauma pain, milk cow, sow mammitis have allodynia.But at present applied to animal
For medicine for relieving pain, often there is the problems such as responding time is long, of high cost or there are side effects.
In view of this, special propose the present invention.
Invention content
First of the present invention is designed to provide a kind of Ketoprofen external used medicine, to alleviate use existing in the prior art
In medicine for relieving pain, often there is technical issues that responding time is long, of high cost or exist.
Second object of the present invention is to provide the preparation method of above-mentioned Ketoprofen external used medicine, this method technique letter
It is single, easy to operate, the Ketoprofen external application that a large amount of man power and material can be saved, effectively improve production efficiency, and be prepared
Drug has good analgesic effect.
Third object of the present invention is to provide above-mentioned Ketoprofen external used medicine answering in preparing external application analgesic drug
With.
Fourth object of the present invention is to provide a kind of external application analgesic drug, to alleviate existing in the prior art be used for
Medicine for relieving pain often there is technical issues that responding time is long, of high cost or exist.
The present invention provides a kind of Ketoprofen external used medicine, the Ketoprofen external used medicine is in terms of 100 parts by weight, including such as
The component of lower parts by weight：
0.1-5 parts of 0.1-30 parts of Ketoprofen, 0.1-20 parts of cosolvent, 0.1-2 parts of skin penetration enhancer and stabilizer, it is remaining
Amount is water.
Further, the Ketoprofen external used medicine includes the component of following parts by weight in terms of 100 parts by weight：
0.1-4 parts of 1-30 parts of Ketoprofen, 2-20 parts of cosolvent, 0.1-1.5 parts of skin penetration enhancer and stabilizer, surplus
For water；
Preferably, the Ketoprofen external used medicine includes the component of following parts by weight in terms of 100 parts by weight：
5-30 parts of Ketoprofen, 3-15 parts of cosolvent, 0.1-1 parts of skin penetration enhancer and 1-3 parts of stabilizer, surplus are
Water.
Further, the cosolvent be selected from arginine, meglumine, histidine, methionine, betadex, Tween 80,
It is one or more in polyethylene glycol 400 or Macrogol 600；
Preferably, the cosolvent is arginine and Macrogol 600；
Preferably, the mass ratio of the arginine and Macrogol 600 is 1-30:1-30.
Further, the one kind of the skin penetration enhancer in Laurocapram, menthol, propylene glycol or eucalyptus oil
Or it is a variety of；
Preferably, the skin penetration enhancer is Laurocapram；
Preferably, the stabilizer is selected from citric acid；
Preferably, the Ketoprofen external used medicine further includes 0.001-5 parts of pigment, preferably 0.001-1 parts, more preferably
0.005-0.1 parts；
Preferably, the pigment is food grade pigment, preferably brilliant blue.
Further, the Ketoprofen external used medicine further includes 0.1-10 parts of emollient, preferably 1-5 parts, more preferably
1-3 parts；
Preferably, the emollient includes glycerine.
Further, the Ketoprofen external used medicine further includes 0.1-20 parts of co-penetrant, preferably 1-15 parts, more preferably
It is 5-10 parts；
Preferably, the penetrant is organic solvent, preferably C1-C4 alcohol, more preferably ethyl alcohol.
The present invention also provides the preparation method of above-mentioned Ketoprofen external used medicine, the preparation method includes：
Cosolvent is added to the water mixing to dissolving, Ketoprofen mixing is then added and extremely dissolves by each component for taking formula ratio,
Stabilizer and skin penetration enhancer mixing are added, pigment and constant volume is eventually adding, obtains the Ketoprofen external used medicine.
Further, before cosolvent is added, first solvent is heated；
Preferably, the temperature of the heat treatment is 50-70 DEG C, preferably 55-65 DEG C.
The ketone Lip river being prepared the present invention also provides above-mentioned Ketoprofen external used medicine or using above-mentioned preparation method
Application of the fragrant external used medicine in preparing external application analgesic drug；
Preferably, the external application analgesic drug is external application analgesic spray.
In addition, be prepared the present invention also provides above-mentioned Ketoprofen external used medicine or using above-mentioned preparation method
Application of the Ketoprofen external used medicine in preparing mastitis for milk cows adjuvant therapy medicaments.
Ketoprofen external used medicine provided by the invention, component include Ketoprofen, cosolvent, skin penetration enhancer and steady
Determine agent.Wherein, Ketoprofen belongs to NSAIDs drugs, as the Ketoprofen external used medicine active constituent, can reduce allodynia
Degree, can play the role of easing pain and diminishing inflammation, cosolvent is added in cooperation, and the compatibility of each component can be made more preferable, cooperation plus
Enter skin penetration enhancer, the Ketoprofen external used medicine provided by the invention outer used time can be made to be more easily absorbed by the skin, reach suction
Keep the good purpose of curative effect well, cooperation is added stabilizer, the stability of Ketoprofen external used medicine can be made stronger, and mutability does not become
Matter, it is cost-effective convenient for storage, by the coordinated between each specific components and proportioning, make Ketoprofen provided by the invention
External used medicine can reduce the degree of allodynia, shorten the time of pain and rehabilitation, avoid the generation of irreversible damage, to
The effect for the treatment of is substantially increased, and has both easy to use, lower-cost advantage.
The preparation method of above-mentioned Ketoprofen external used medicine provided by the invention, it is easy to operate, it is added by specific component
Sequentially and to specific operating procedures such as mixing, the dissolvings of component, it enables to each component to cooperate, obtains analgesic effect
Good, quick, easy to use and at low cost Ketoprofen external used medicine.
Specific implementation mode
Technical scheme of the present invention is clearly and completely described below in conjunction with embodiment, it is clear that described reality
It is a part of the embodiment of the present invention to apply example, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this field
The every other embodiment that art personnel are obtained without making creative work belongs to the model that the present invention protects
It encloses.
The present invention provides a kind of Ketoprofen external used medicines, in terms of 100 parts by weight, include the component of following parts by weight：
0.1-30 parts of Ketoprofen, 0.1-20 parts of cosolvent, 0.1-2 parts of skin penetration enhancer, 0.1-5 parts of stabilizer and face
0.001-5 parts of material, surplus is water.
Wherein, Ketoprofen belongs to a kind of efficient non-steroidal anti-inflammatory drug (NSAIDs), have it is anti-inflammatory, analgesia, it is antipyretic
Effect, it is mainly by the activity of reversible inhibition cyclooxygenase (COXs), proinflammatory peptide or lipoxidase (LOXs), to inhibit
The biosynthesis for causing Inflammatory substances prostaglandin (PGs), leukotriene (LTs) and thromboxane (TXs) makes bradykinin release reduce,
And then play its good anti-inflammatory, analgesia and refrigeration function.In the present invention, using Ketoprofen as the Ketoprofen external used medicine
Active constituent can reduce the degree of allodynia, can play the role of easing pain and diminishing inflammation.Its content for example can be, but not
It is limited to 0.1 part, 1 part, 5 parts, 10 parts, 15 parts, 20 parts, 25 parts or 30 parts.
Cosolvent is water-soluble, mostly low molecular compound, can form shla molecule in water with slightly solubility component
Between complex compound, associated matter or double salt etc., to increase the solubility of drug in a solvent.In the present invention, hydrotropy is added in cooperation
Agent can make the compatibility of each component more preferable.Its content for example can be, but be not limited to 0.1 part, 1 part, 5 parts, 10 parts, 15 parts
Or 20 parts.
Skin penetration enhancer (abbreviation transdermal enhancer) means that can accelerate drug penetrates the speed of skin without to skin shape
At the serious substance stimulated and damage.The mechanism of action of transdermal enhancer is mainly penetrated by reversible change skin texture
Skin simultaneously reduces drug by resistance suffered by skin, achievees the purpose that promote drug systemic Absorption or local treatment.In the present invention
In, skin penetration enhancer is added in cooperation, and the Ketoprofen external used medicine provided by the invention outer used time can be made to be more easy to be inhaled by skin
It receives, achievees the purpose that good absorbing curative effect is good.Its content for example can be, but be not limited to 0.1 part, 0.5 part, 1 part, 1.5 parts or 2
Part.
Stabilizer can increase the stability of solution or mixture, and stabilizer can slow down reaction, keep chemical balance, drop
Low surface tension, the effects that preventing light, thermal decomposition or oxygenolysis.In the present invention, stabilizer is added in cooperation, can make ketone Lip river
The stability of fragrant external used medicine is stronger, and mutability is not rotten, cost-effective convenient for storage.Its content for example can be, but unlimited
In 0.1 part, 1 part, 2 parts, 3 parts, 4 parts or 5 parts.
Ketoprofen external used medicine provided by the invention makes this hair by the coordinated between each specific components and proportioning
The Ketoprofen external used medicine of bright offer can reduce the degree of allodynia, shorten the time of pain and rehabilitation, avoid irreversible
The generation of damage to substantially increase the effect for the treatment of, and has both easy to use, lower-cost advantage.
In one preferred embodiment, Ketoprofen external used medicine includes the group of following parts by weight in terms of 100 parts by weight
Point：
1-30 parts of Ketoprofen, 2-20 parts of cosolvent, 0.1-1.5 parts of skin penetration enhancer, 0.1-4 parts of stabilizer and pigment
0.001-1 parts, surplus is water.
Preferably, Ketoprofen external used medicine includes the component of following parts by weight in terms of 100 parts by weight：
5-30 parts of Ketoprofen, 3-15 parts of cosolvent, 0.1-1 parts of skin penetration enhancer, 1-3 parts of stabilizer and pigment
0.005-0.1 parts, surplus is water.
It is further adjusted and is optimized by the proportioning to component so that Ketoprofen external used medicine provided by the invention
With better analgesic effect, better efficacy takes effect faster, and utmostly cost-effective.
In one preferred embodiment, cosolvent is selected from arginine, meglumine, histidine, methionine, times his ring and pastes
It is one or more in essence, Tween 80, polyethylene glycol 400 or Macrogol 600.
Preferably, cosolvent is arginine and Macrogol 600.
When select arginine and Macrogol 600 as the present invention in cosolvent when, can preferably increase each component
Solubility in a solvent improves the compatibility of each component in Ketoprofen external used medicine.
Preferably, the mass ratio of arginine and Macrogol 600 is 1-30:1-30, such as can be, but it is not limited to 1:1、
1:2、1:3、1:5、1:10、1:15、1:20、1:30、30:1、20:1、15:1、10:1、5:1、3:1 or 2:1.
In one preferred embodiment, skin penetration enhancer is selected from Laurocapram, menthol, propylene glycol or eucalyptus
It is one or more in oil.
Preferably, skin penetration enhancer is Laurocapram.
When selecting Laurocapram as skin penetration enhancer of the invention, Ketoprofen provided by the invention can be made
The external used medicine outer used time is more easily absorbed by the skin, and achievees the purpose that good absorbing curative effect is good.
Preferably, stabilizer is selected from citric acid.
When selecting citric acid as stabilizer of the invention, the stability of Ketoprofen external used medicine can be made stronger, no
Mutability is rotten, cost-effective convenient for storage.
Preferably, the Ketoprofen external used medicine further includes pigment.
Pigment is exactly the substance that object or solution can be made to catch color.In the present invention, pigment is added in cooperation, facilitates clinic
In use, whether more convenient observation drug all covers tissue, especially big mammitis of animal, Skeletal trauma etc..
Its content is 0.001-5 parts, such as can be, but be not limited to 0.001 part, 0.005 part, 0.01 part, 0.1 part, 1
Part, 2 parts, 3 parts, 4 parts or 5 parts；Preferably 0.001-1 parts, more preferably 0.005-0.1 parts.
Preferably, pigment is food grade pigment, preferably brilliant blue.
Food grade pigment is selected, can ensure can be safe and harmless if being eaten by mistake by animal, does not cause to pacify to user
Full hidden danger.
In one preferred embodiment, Ketoprofen external used medicine further includes emollient.
Emollient refers to that skin is helped to keep soft, smooth and pliable appearance preparation.Emollient is rested on by them
Ability in skin surface or cuticula is had an effect.Emollient, energy is added in Ketoprofen external used medicine provided by the invention
Stimulation of the drug Ketoprofen external used medicine to skin is enough effectively reduced, the comfort level of user is greatlyd improve.
Wherein, the content of emollient is 0.1-10 parts, such as can be, but be not limited to 0.1 part, 1 part, 2 parts, 3 parts, 4 parts,
5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, preferably 1-5 parts, more preferably 1-3 parts.
Preferably, emollient includes glycerine.
In one preferred embodiment, Ketoprofen external used medicine further includes co-penetrant.
Co-penetrant can be used cooperatively with bleeding agent, by the synergistic effect of the two, reinforce the transdermal effect of drug, be increased
Waste is reduced while strong curative effect.
Wherein, the content of co-penetrant is 0.1-20 parts, such as can be, but be not limited to 0.1 part, 1 part, 3 parts, 5 parts, 7
Part, 10 parts, 12 parts, 15 parts, 18 parts or 20 parts, preferably 1-15 parts, more preferably 5-10 parts；
Preferably, the penetrant is organic solvent, preferably C1-C4 alcohol, more preferably ethyl alcohol.
It is best with the synergistic effect of bleeding agent when selecting ethyl alcohol as co-penetrant, transdermal effect can be made maximum
Change.
The present invention also provides the preparation methods of above-mentioned Ketoprofen external used medicine, including：
Cosolvent is added to the water mixing to dissolving, Ketoprofen mixing is then added and extremely dissolves by each component for taking formula ratio,
Stabilizer and skin penetration enhancer mixing are added, pigment and constant volume is eventually adding, obtains Ketoprofen external used medicine.
The preparation method of above-mentioned Ketoprofen external used medicine provided by the invention, it is easy to operate, it is added by specific component
Sequentially and to specific operating procedures such as mixing, the dissolvings of component, it enables to each component to cooperate, obtains analgesic effect
Good, quick, easy to use and at low cost Ketoprofen external used medicine.
In one preferred embodiment, before cosolvent is added, first water is heated.
More preferably be conducive to the dissolving of cosolvent after water is heated in advance, save the time.
Preferably, the temperature of heat treatment is 50-70 DEG C, such as can be, but is not limited to 50 DEG C, 55 DEG C, 60 DEG C, 65 DEG C
Or 70 DEG C, preferably 55-65 DEG C.
In one preferred embodiment, it using stirring or ultrasonic mixing, preferably stirs and evenly mixs.
Carried out in the way of stirring mixing can while reaching mixed effect effectively save instrument cost.
Preferably, be stirred with the speed of 70-90r/min, such as can be, but be not limited to 70r/min, 75r/min,
80r/min or 85r/min, preferably 75-85r/min.
The ketone Lip river being prepared the present invention also provides above-mentioned Ketoprofen external used medicine or using above-mentioned preparation method
Application of the fragrant external used medicine in preparing external application analgesic drug.Wherein, external application analgesic drug for example can be, but be not limited to external application
Ease pain spray or external application analgesic paint.
Preferably, external application analgesic drug is external application analgesic spray, and spray enables to drug not by dauber
In the case of affected part can be carried out uniformly, comprehensive application and covering, ensure that the active area of drug.In addition, spray is applied
Shi Wuxu with affected part is practical is contacted, avoid contact with stress reaction caused by pain, to improve therapeutic effect, shorten treatment
Time.
In addition, be prepared the present invention also provides above-mentioned Ketoprofen external used medicine or using above-mentioned preparation method
Application of the Ketoprofen external used medicine in preparing mastitis for milk cows adjuvant therapy medicaments.
With reference to specific embodiment and comparative example, the invention will be further described.
Embodiment 1
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
74.8 parts of 0.1 part of Ketoprofen, 20 parts of betadex, 0.1 part of menthol and water.
Embodiment 2
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
67.8 parts of 30 parts of Ketoprofen, 0.1 part of histidine, 2 parts of propylene glycol and water.
Embodiment 3
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
15 parts of Ketoprofen, 8 parts of arginine, 2 parts of Macrogol 600,0.5 part of Laurocapram, 2 parts of citric acid and water
72.5 parts.
Embodiment 4
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
0.1 part of Ketoprofen, 20 parts of betadex, 0.1 part of menthol, 10 parts of glycerine, 0.1 part of ethyl alcohol and water 64.699
Part.
Embodiment 5
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
47.6 parts of 30 parts of Ketoprofen, 0.1 part of histidine, 2 parts of propylene glycol, 0.1 part of glycerine, 20 parts of ethyl alcohol and water.
Embodiment 6
A kind of Ketoprofen external used medicine is present embodiments provided, the component of following parts by weight is included：
15 parts of Ketoprofen, 8 parts of arginine, 2 parts of Macrogol 600,0.5 part of Laurocapram, 2 parts of citric acid, brilliant blue
57.49 parts of 0.01 part, 5 parts of glycerine, 10 parts of ethyl alcohol and water.
Embodiment 7
A kind of Ketoprofen external used medicine is present embodiments provided, by being prepared following preparation method：
(a) 72.5 parts of water are heated to 60 DEG C, 8 parts of arginine are added by the Ketoprofen external used medicine that Example 3 provides,
80r/min stirs 8-10min to being completely dissolved；
(b) 2 parts of Macrogol 600 is added, stirs evenly；
(c) 15 parts of Ketoprofen is added, 80r/min stirs 15-20min to being completely dissolved；
(d) stop heating, sequentially add 0.5 part of 2 parts of citric acid and Laurocapram, stir evenly for use, constant volume, sterilizing
It is filling afterwards.
Embodiment 8
A kind of Ketoprofen external used medicine is present embodiments provided, by being prepared following preparation method：
(a) 57.49 parts of water are heated to 60 DEG C, 8 parts of arginine are added by the Ketoprofen external used medicine that Example 6 provides,
80r/min stirs 8-10min to being completely dissolved；
(b) 2 parts of Macrogol 600 is added, stirs evenly；
(c) 15 parts of Ketoprofen is added, 80r/min stirs 15-20min to being completely dissolved；
(d) stop heating, sequentially add 10 parts of 2 parts of citric acid, 0.5 part of Laurocapram, 5 parts of glycerine and ethyl alcohol, stir
It is uniformly for use；
(e) above-mentioned solution is added after dissolving 0.01 part of brilliant blue in alcohol, and constant volume is filling after sterilizing.
Comparative example 1
This comparative example provides a kind of Ketoprofen external used medicine, includes the component of following parts by weight：
70.9 parts of 0.05 part of Ketoprofen, 22 parts of betadex, 0.05 part of menthol and water.
Comparative example 2
This comparative example provides a kind of Ketoprofen external used medicine, includes the component of following parts by weight：
82.5 parts of 15 parts of Ketoprofen, 0.5 part of Laurocapram, 2 parts of citric acid and water.
Comparative example 3
This comparative example provides a kind of Ketoprofen external used medicine, includes the component of following parts by weight：
73 parts of 15 parts of Ketoprofen, 8 parts of arginine, 2 parts of Macrogol 600,2 parts of citric acid and water.
In order to Ketoprofen external used medicine row further instruction provided by the invention, be tested as follows：
1 pharmaceutical stability of experimental example is tested
1, strong illumination is tested
Sample bright light test result see the table below 1：
1 strong illumination experiment investigation result (1000ml/ bottles) of table
From the experimental result of table 1 as can be seen that using ketone made of 1-8 of the embodiment of the present invention components provided and proportioning
The stability of ibuprofen external used medicine, character, pH value and Ketoprofen content under strong illumination is all significantly larger than Comparison study
Ketoprofen external used medicine made of the component and proportioning that example 1-3 is provided, illustrates through the collaboration between each specific components and proportioning
Cooperation, makes the pharmaceutical stability of Ketoprofen external used medicine provided by the invention greatly enhance, and is suitable for clinical application.Meanwhile it applying
Embodiment 7 and embodiment 8 prepared by preparation method provided by the invention, effect are slightly good compared with embodiment 3 and embodiment 6, say
The effect of the bright Ketoprofen external used medicine being prepared using preparation method provided by the invention is more preferable.
2, hot test
In order to save experimental cost, the stronger embodiment 3 of strong illumination experiment Chinese pharmacology stability and embodiment 6 is selected to do
Hot test, simultaneous selection comparative example 1 compare.High-temperature sample test result see the table below 2：
Result (1000ml/ bottles) is investigated in 2 hot test of table
As can be seen that applying made of the component and proportioning of the offer of the embodiment of the present invention 3 and 6 from the experimental result of table 2
The stability of Ketoprofen external used medicine, character at high temperature, pH value and Ketoprofen content is all significantly larger than Comparison study example 1
Ketoprofen external used medicine made of the component and proportioning of offer, illustrates through the coordinated between each specific components and proportioning,
So that the pharmaceutical stability of Ketoprofen external used medicine provided by the invention is greatly enhanced, is suitable for clinical application.
3, accelerated test
In order to save experimental cost, the stronger embodiment 3 of strong illumination experiment Chinese pharmacology stability and embodiment 6 is selected to do
Hot test, simultaneous selection comparative example 1 compare.High-temperature sample test result see the table below 3：
3 accelerated test of table investigates result (1000ml/ bottles)
As can be seen that applying made of the component and proportioning of the offer of the embodiment of the present invention 3 and 6 from the experimental result of table 3
Ketoprofen external used medicine stores stability all significantly larger than applications pair of the character after long-time, pH value and Ketoprofen content
Ketoprofen external used medicine made of the component and proportioning that ratio 1 provides, illustrates through the collaboration between each specific components and proportioning
Cooperation, makes the pharmaceutical stability of Ketoprofen external used medicine provided by the invention greatly enhance, and is suitable for clinical application.
2 clinical effect trial of experimental example
One, mastitis for milk cows
1, experimental animal selection criteria
Milk cow inclusion criteria：It is that the milk cow in lactation period breast with actual clinical type mammitis has a tidal wave of through clinical diagnosis
The clinical symptoms etc. of red, swelling, fever and pain.
2, experimental animal grouping and administration
30 experiment infected cattles are assigned to 2 test groups (I, II, every group 15) by random, make every group of infected cattle as possible
Morbidity severity it is almost the same.
The Ketoprofen external used medicine for taking the embodiment of the present invention 3 to provide, using cow breast tissue entirety even application, 1 day 2
It is secondary, it is used in conjunction 3 days；Cefquinome sulfate breast injection (lactation period) 1 time 1, interval 12h are administered once, are used in conjunction 6 times, each group tool
Body drug administration information is shown in Table 4.During entire experiment, all experiment infected cattles no longer give any other antibacterials and anti-inflammatory drug.
3, experiment packet and administration
The experiment of table 4 grouping and administration
4, infected cattle clinicing symptom observation and evaluation are tested
Before first 0 day of administration, each administration, the 1st, 3,7,14 day after last time administration, the spirit of milk cow is observed
Situation, breast local symptom, milk character, and given a mark according to following symptom scores standards (table 5).
5 symptom scores standard of table
5, milk cow pain reaction observe and evaluate
Per group selection 15 cow head, the 0h before Ketoprofen is administered, every time 0.5h, 1h after administration, 2h, 4h, 6h,
8h, 12h and for 24 hours, 0.5h, 1h after last time is administered, 2h, 4h, 6h, 8h, 12h, for 24 hours, the pain of 36h, 48h observation milk cow it is anti-
It answers, and gives a mark according to pain reaction standards of grading (table 6).
6 pain reaction standards of grading of table
6, test results and analysis
6.1 experiment infected cattle clinical manifestations
Observe all infected cattles 0 day before administration, every time before administration, last time be administered after the 1st, 3,7,14 day spiritual shape
Condition, breast local symptom, milk character score to it by above-mentioned standard.To the breast local symptom of each group test ox, breast
Juice character, mental status scoring are for statistical analysis, are as a result shown in Table 7 respectively, table 8, table 9.
7 different time points test ox breast local symptom appraisal result of table counts
| Observation time (day) | I groups | II groups |
| Administration 0 day | 2.60±0.62 | 2.63±0.56 |
| Administration 1 day | 2.27±0.52 | 2.43±0.50 |
| Administration 2 days | 1.67±0.61* | 1.97±0.41* |
| Administration 3 days | 0.83±0.75* | 1.13±0.57* |
| It is discontinued 1 day | 0.39±0.50* | 0.61±0.50* |
| It is discontinued 3 days | 0.11±0.42* | 0.32±0.55* |
| It is discontinued 7 days | 0.04±0.19* | 0.08±0.27* |
| It is discontinued 14 days | 0.00±0.00* | 0.00±0.00* |
Note：Has identical lowercase letter indication difference significantly (p≤0.05)；" * " indicates significant difference (p≤0.05).
The above results show acute mastitis infected cattle after application Ketoprofen external medication provided by the invention,
The breast local symptom of infected cattle can fast and effeciently be improved.
8 different time points test ox milk character appraisal result of table counts
Note：Has identical lowercase letter indication difference significantly (p≤0.05)；" * " indicates significant difference (p≤0.05).
The above results show acute mastitis infected cattle after application Ketoprofen external medication provided by the invention,
The milk character of infected cattle can fast and effeciently be improved.
8 different time points test ox state of mind appraisal result of table counts
| Observation time (day) | I groups | II groups |
| Administration 0 day | 1.47±0.51 | 1.53±0.51 |
| Administration 1 day | 1.03±0.41 | 1.20±0.41 |
| Administration 2 days | 0.67±0.55* | 0.83±0.53* |
| Administration 3 days | 0.47±0.63* | 0.57±0.57* |
| It is discontinued 1 day | 0.18±0.39* | 0.39±0.50* |
| It is discontinued 3 days | 0.07±0.26* | 0.25±0.52* |
| It is discontinued 7 days | 0.04±0.19* | 0.08±0.27* |
| It is discontinued 14 days | 0.00±0.00* | 0.00±0.00* |
Note：Has identical lowercase letter indication difference significantly (p≤0.05)；" * " indicates significant difference (p≤0.05).
The above results show acute mastitis infected cattle after application Ketoprofen external medication provided by the invention,
The state of mind of infected cattle can fast and effeciently be improved.
6.2 experiment infected cattle pain reaction appraisal results
9 different time points test ox pain reaction appraisal result of table counts
The above results show that acute mastitis infected cattle, can after application Ketoprofen external medication provided by the invention
Fast and effeciently alleviate the pain of infected cattle.
7, conclusion (of pressure testing)
Compared with Cefquinome sulfate breast injection is used alone, it is combined Ketoprofen external used medicine energy provided by the invention
More effective alleviation milk cow lassitude and appetite drink are intended to decline, and can enhance milking compliance；It is combined ketone Lip river provided by the invention
Fragrant external used medicine can more rapidly, thoroughly alleviate the area's swelling of infected cattle breast, eliminate newborn area lump caused by mammitis；The combination present invention carries
The Ketoprofen external used medicine of confession can more effectively reduce the exception such as milk floccule, ziega, and milk and milking capacity is made to obtain
Faster restore；The Milk Production of milk cow in lactation period can more effectively be restored by being combined Ketoprofen external used medicine provided by the invention, be carried
High output of milk resume speed and recovery increase the economic benefit in pasture to ratio before the onset.
Two, pet Postoperative Analgesia After
1, Guangzhou pet clinic, dog surgery (cases such as fracture) operation case is 10 total, and therapeutic regimen is as follows：
2, pain scores table
3, pain scores table result counts
As seen from the above table, morphine hydrochloride combines the analgesic effect of Ketoprofen external used medicine provided by the invention and is better than and individually makes
With morphine hydrochloride group.Illustrate, by the coordinated between each specific components and proportioning, to make Ketoprofen external application provided by the invention
Drug can reduce the degree of allodynia, shorten the time of pain and rehabilitation, avoid the generation of irreversible damage, to significantly
The effect for the treatment of is improved, and has both easy to use, lower-cost advantage.
Finally it should be noted that：The above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Present invention has been described in detail with reference to the aforementioned embodiments for pipe, it will be understood by those of ordinary skill in the art that：Its according to
So can with technical scheme described in the above embodiments is modified, either to which part or all technical features into
Row equivalent replacement；And these modifications or replacements, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
1. a kind of Ketoprofen external used medicine, which is characterized in that the Ketoprofen external used medicine is including as follows in terms of 100 parts by weight
The component of parts by weight：
0.1-30 parts of Ketoprofen, 0.1-20 parts of cosolvent, 0.1-2 parts of skin penetration enhancer and 0.1-5 parts of stabilizer, surplus are
Water.
2. Ketoprofen external used medicine according to claim 1, which is characterized in that the Ketoprofen external used medicine is with 100 weights
Part meter is measured, the component of following parts by weight is included：
1-30 parts of Ketoprofen, 2-20 parts of cosolvent, 0.1-1.5 parts of skin penetration enhancer and 0.1-4 parts of stabilizer, surplus are
Water；
Preferably, the Ketoprofen external used medicine includes the component of following parts by weight in terms of 100 parts by weight：
1-3 parts of 5-30 parts of Ketoprofen, 3-15 parts of cosolvent, 0.1-1 parts of skin penetration enhancer and stabilizer, surplus is water.
3. Ketoprofen external used medicine according to claim 1, which is characterized in that the cosolvent is selected from arginine, Portugal's first
It is one or more in amine, histidine, methionine, betadex, Tween 80, polyethylene glycol 400 or Macrogol 600；
Preferably, the cosolvent is arginine and Macrogol 600；
Preferably, the mass ratio of the arginine and Macrogol 600 is 1-30:1-30.
4. Ketoprofen external used medicine according to claim 1, which is characterized in that the skin penetration enhancer is selected from bay
It is one or more in Azone, menthol, propylene glycol or eucalyptus oil；
Preferably, the skin penetration enhancer is Laurocapram；
Preferably, the stabilizer is selected from citric acid；
Preferably, the Ketoprofen external used medicine further includes 0.001-5 parts of pigment, preferably 0.001-1 parts, more preferably
0.005-0.1 parts；
Preferably, the pigment is food grade pigment, preferably brilliant blue.
5. according to claim 1-4 any one of them Ketoprofen external used medicines, which is characterized in that the Ketoprofen external used medicine
It further include 0.1-10 parts, preferably 1-5 parts, more preferably 1-3 parts of emollient；
Preferably, the emollient includes glycerine.
6. according to claim 1-4 any one of them Ketoprofen external used medicines, which is characterized in that the Ketoprofen external used medicine
It further include 0.1-20 parts, preferably 1-15 parts, more preferably 5-10 parts of co-penetrant；
Preferably, the penetrant is organic solvent, preferably C1-C4 alcohol, more preferably ethyl alcohol.
7. the preparation method of Ketoprofen external used medicine as claimed in any one of claims 1 to 6, which is characterized in that the preparation side
Method includes：
Cosolvent is added to the water mixing to dissolving, Ketoprofen mixing is then added to dissolving, then add by each component for taking formula ratio
Enter stabilizer and skin penetration enhancer mixing, is eventually adding pigment and constant volume, obtains the Ketoprofen external used medicine.
8. preparation method according to claim 7, which is characterized in that before cosolvent is added, first heated to solvent
Processing；
Preferably, the temperature of the heat treatment is 50-70 DEG C, preferably 55-65 DEG C.
9. the preparation method described in Ketoprofen external used medicine as claimed in any one of claims 1 to 6 or use claim 7 or 8
Application of the Ketoprofen external used medicine being prepared in preparing external application analgesic drug；
Preferably, the external application analgesic drug is external application analgesic spray.
10. the preparation side described in Ketoprofen external used medicine as claimed in any one of claims 1 to 6 or use claim 7 or 8
Application of the Ketoprofen external used medicine that method is prepared in preparing mastitis for milk cows adjuvant therapy medicaments.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671369A (en) * | 2002-08-01 | 2005-09-21 | 阿麦里尼工业药物联合中心科学研究室 | Topical formulations containing ketoprofen stabilised with sulisobenzone |
| CN1738612A (en) * | 2001-12-11 | 2006-02-22 | 埃斯蒂文博士实验室股份有限公司 | Drinkable preparation comprising ketoprofen and the use thereof in the simultaneous treatment of a group of animals for processes which are accompanied by fever, inflammation and/or pain |
| CN103156803A (en) * | 2011-12-08 | 2013-06-19 | 杭州赛利药物研究所有限公司 | Ketoprofen gel and preparation method thereof |
| CN107007574A (en) * | 2017-05-16 | 2017-08-04 | 蔡志浩 | A kind of Ketoprofen Babu cream |
-
2018
- 2018-06-29 CN CN201810721306.4A patent/CN108653262B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1738612A (en) * | 2001-12-11 | 2006-02-22 | 埃斯蒂文博士实验室股份有限公司 | Drinkable preparation comprising ketoprofen and the use thereof in the simultaneous treatment of a group of animals for processes which are accompanied by fever, inflammation and/or pain |
| CN1671369A (en) * | 2002-08-01 | 2005-09-21 | 阿麦里尼工业药物联合中心科学研究室 | Topical formulations containing ketoprofen stabilised with sulisobenzone |
| CN103156803A (en) * | 2011-12-08 | 2013-06-19 | 杭州赛利药物研究所有限公司 | Ketoprofen gel and preparation method thereof |
| CN107007574A (en) * | 2017-05-16 | 2017-08-04 | 蔡志浩 | A kind of Ketoprofen Babu cream |
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