CN105288016B - External traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis and preparation method thereof - Google Patents
External traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis and a preparation method thereof. The external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is an O/W type dispersion, the average grain diameter of a dispersion phase is 0.5 micron, and the external traditional Chinese medicine emulsion is called a microemulsion preparation or a sub-nanoemulsion preparation in pharmaceutics; the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared by processing the following traditional Chinese medicinal materials in parts by weight: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of psoralea fruit, 0.07 part of scorpion, 0.7 part of drynaria rhizome and 0.7 part of prepared rhizome of rehmannia, and the content of the traditional Chinese medicinal materials in the finally prepared emulsion is 0.22 percent. The preparation has the effects of nourishing liver and kidney, strengthening bones and muscles, promoting blood circulation and removing obstruction in channels, and is suitable for treating orthopedic diseases such as limb bone joint pain, neck and waist pain and the like caused by liver and kidney deficiency and tendon and leg stasis; the medicine can directly act on the affected part through the skin, and has the characteristic of obvious drug effect.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicine preparations, relates to a preparation method of an external traditional Chinese medicine preparation for preventing and treating knee osteoarthritis, and particularly relates to an external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis and a preparation method thereof.
Background
Osteoarthritis is a chronic joint disease mainly changing degenerative changes and secondary hyperosteogeny of articular cartilage surfaces, represents the aging of joints, and is called as senile arthritis. Old knee osteoarthritis belongs to the field of traditional Chinese medicine bone rheumatism and is a common clinical disease and frequently encountered disease in orthopedics and traumatology. The initial epidemiological survey in China shows that the incidence rate is 30 percent, the main symptoms are gradually aggravated knee joint pain, the life quality and the social productivity of patients are seriously harmed, and the wide attention of the medical field is paid.
The western medicine therapy is single and has poor curative effect. The traditional Chinese medicine adopts comprehensive treatment methods such as oral administration and external treatment of traditional Chinese medicines, and the like, and can achieve good curative effect. For example, CN 102370838A discloses an oral Chinese medicinal prescription for treating osteoarthritis, and CN 102302616A discloses a cataplasm for treating knee osteoarthritis and a preparation method thereof, which have good curative effects. However, the existing external preparation for treating knee osteoarthritis cannot be well combined with massage acupuncture therapy. It is clearly important to develop an external preparation for the prevention and treatment of osteoarthritis in combination with massage acupuncture therapy.
Disclosure of Invention
In order to overcome the defects and shortcomings in the prior art, the invention aims to provide an external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
The invention also aims to provide a preparation method of the externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
The purpose of the invention is realized by the following technical scheme:
the externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is an O/W type dispersion, the average grain diameter of a dispersion phase is 0.5 micron, and the emulsion is called a microemulsion preparation or a sub-nanoemulsion preparation in pharmaceutics; the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared by processing the following traditional Chinese medicinal materials in parts by weight: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of psoralea fruit, 0.07 part of scorpion, 0.7 part of drynaria rhizome and 0.7 part of prepared rhizome of rehmannia. The content of the Chinese medicinal materials in the final emulsion is 0.22%.
A preparation method of an external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis comprises the following steps:
(1) preparing an oil phase: collecting Eucommiae cortex 0.42 weight parts, sanguis Draxonis 0.07 weight parts and fructus Psoraleae 0.25 weight parts, reflux-extracting with ethanol, concentrating the filtrate to fluid extract, or extracting the medicinal materials with supercritical CO2Extracting and collecting extract liquor; then vacuum drying the clear paste or extract, crushing, adding a fat-soluble solvent to 50-100 parts by mass, heating for dissolving, and filtering to obtain an oil phase;
(2) preparing an aqueous phase: taking the dregs of the decoction obtained in the step (1), 0.07 part by mass of scorpion, 0.7 part by mass of rhizoma drynariae and 0.7 part by mass of rehmannia glutinosa, decocting the mixture for 2-3 times with water, decocting the mixture for 1-2 hours each time, filtering the decoction, combining the filtrates, and concentrating the mixture to 460 parts by mass to obtain a water phase;
(3) preparing an emulsion: mixing 40 parts by mass of a transdermal enhancer, 75-125 parts by mass of a cosurfactant and 275-375 parts by mass of a surfactant with 50-100 parts by mass of the oil phase prepared in the step (1), and adding 460 parts by mass of the water phase prepared in the step (2) under the condition of homogenizing or grinding to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
The fat-soluble solvent in the step (1) is at least one of isopropyl myristate (IPM), isopropyl palmitate (IPP), Ethyl Oleate (EO), medium-chain triglyceride (MCT) and olive oil (LCT).
The ethanol reflux extraction process in the step (1) comprises the following steps: extracting with ethanol under reflux for 2-4 times, wherein the reflux extraction time is 1-2 hours each time, filtering, combining the filtrates obtained each time, and concentrating to obtain fluid extract; wherein, the ratio of the volume of the ethanol added in each reflux extraction to the total mass of the eucommia, the dragon's blood and the psoralea fruit is preferably (6-12) parts by volume: 1 part by mass. The ethanol used in the ethanol reflux extraction is preferably 70 to 95 percent ethanol.
The supercritical CO in the step (1)2The extraction process comprises the following steps: pulverizing Eucommiae cortex, sanguis Draxonis and fructus Psoraleae into coarse powder, adding entrainer, soaking for 1 hr, and performing supercritical CO2Extracting and collecting extract liquor; wherein, the ratio of the total mass of the eucommia bark, the dragon's blood and the psoralea fruit to the volume of the entrainer is preferably 1 part by mass: (1-2) parts by volume.
The supercritical CO2The extraction pressure was 28MPa, the temperature was 55 ℃ and the time was 150 minutes. The entrainer is preferably 95% ethanol.
The percentages of ethanol in the invention are volume percentages.
The ratio of the volume of water added in each decoction in the step (2) to the total mass of the eucommia ulmoides, the dragon's blood, the fructus psoraleae, the scorpion, the rhizoma drynariae and the rehmannia glutinosa is preferably (8-10) parts by volume: 1 part by mass.
The surfactant described in the step (3) is preferably at least one of polysorbate 80, polysorbate 60, polysorbate 20, polyoxyethylene castor oil (Cremephor EL) and polyoxyethylene hydrogenated castor oil (Cremephor RH 40).
The cosurfactant in the step (3) is at least one of ethanol, isopropanol, polyethylene glycol 200, propylene glycol and glycerol.
The transdermal enhancer in the step (3) is laurocapram
A ketone.
The principle of the invention is as follows: the extraction of effective components and the preparation of emulsion are carried out according to the properties of the effective components contained in the traditional Chinese medicinal materials in the prescription and the principle of similar compatibility. The invention is carried out according to the principle that the medicine is directly acted on the affected part and exerts the curative effect through transdermal absorption.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis has the effects of tonifying liver and kidney, strengthening bones and muscles, promoting blood circulation and removing obstruction in channels, and is suitable for treating orthopedic diseases such as limb bone joint pain, neck, waist and leg pain caused by liver and kidney deficiency and tendon and vessel stasis; the medicine can directly act on the affected part through the skin, and has the characteristic of obvious drug effect.
Compared with the prior art, the invention can obtain better clinical curative effect by changing the administration route and combining other treatment means (such as massage manipulation, combination with internal medicine taking and the like). Aiming at the prevention and treatment of knee osteoarthritis, compared with a kidney-tonifying and tendon-strengthening biphasic capsule (patent number: CN 102370838A), the external emulsion provided by the invention changes the administration route, not only improves the curative effect, but also has the following advantages: (1) reduce organ damage caused by long-term oral administration; (2) the oral administration of the traditional Chinese medicine is a systemic treatment mode, has larger dosage, can reduce the dosage of the medicine through local target administration, uses fewer medicinal materials for achieving the curative effect and reduces the cost; (3) the medicine can directly act on the affected part through transdermal absorption to play a role, and target treatment is performed more specifically; (4) the external administration mode can better combine with other traditional Chinese medicine therapies such as massage acupuncture and moxibustion and the like, thereby improving the curative effect and better playing the role of the medicine; this point has been verified clinically by comparison with other common topical agents.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1
The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared according to the following steps:
(1) the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by mass: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of malaytea scurfpea fruit, 0.07 part of scorpion, 0.7 part of rhizoma drynariae and 0.7 part of prepared rhizome of rehmannia;
(2) extracting eucommia bark, dragon's blood and fructus psoraleae twice by using 70% ethanol in a refluxing way, wherein the ratio of the volume of the 70% ethanol added in each refluxing extraction to the total mass of the eucommia bark, the dragon's blood and the fructus psoraleae is 6 parts by volume: 1 part by mass, reflux extracting for 2 hours, filtering, combining the obtained filtrates each time, recovering ethanol and concentrating to obtain clear paste, vacuum drying, pulverizing, adding fat-soluble solvent isopropyl myristate (IPM) to 100 parts by mass, heating to dissolve, filtering to obtain oil phase for use;
(3) decocting the dregs of the decoction obtained in the step (2) with scorpion, rhizoma drynariae and prepared rhizome of rehmannia twice, wherein the volume of water added in each decoction is 10 parts by volume of the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the rhizoma drynariae and the prepared rhizome of rehmannia: 1 part by mass, decocting for 2 hours, filtering, combining the filtrates, and concentrating to 460 parts by mass as a water phase for later use;
(4) taking 40 parts by mass of lauryl nitrogen
And (3) adding 125 parts by mass of ethanol into the ketone, stirring the mixture to dissolve the mixture, adding 275 parts by mass of polysorbate 80 into the mixture, mixing the mixture with 100 parts by mass of the oil phase prepared in the step (2), homogenizing the mixture, and slowly adding 460 parts by mass of the water phase prepared in the step (3) to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
Example 2
The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared according to the following steps:
(1) the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by mass: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of malaytea scurfpea fruit, 0.07 part of scorpion, 0.7 part of rhizoma drynariae and 0.7 part of prepared rhizome of rehmannia;
(2) reflux-extracting Eucommiae cortex, sanguis Draxonis and fructus Psoraleae with 95% ethanol once, wherein the ratio of the volume of 95% ethanol added to the total mass of Eucommiae cortex, sanguis Draxonis and fructus Psoraleae is 12 parts by volume: 1 part by mass, extracting under reflux for 1 hour, filtering, mixing the filtrates each time, recovering ethanol and concentrating to obtain fluid extract, vacuum drying, pulverizing, adding isopropyl palmitate (IPP) to 50 parts by mass, heating to dissolve, and filtering to obtain oil phase;
(3) decocting the dregs of the decoction obtained in the step (2) with scorpion, rhizoma drynariae and prepared rhizome of rehmannia for three times, wherein the volume of water added in each decoction is 8 parts by volume of the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the rhizoma drynariae and the prepared rhizome of rehmannia: 1 part by mass, decocting for 1 hour, filtering, combining the filtrates, and concentrating to 460 parts by mass as a water phase for later use;
(4) taking 40 parts by mass of lauryl nitrogen
And (3) adding 75 parts by mass of isopropanol into the ketone, stirring to dissolve the mixture, adding 375 parts by mass of polysorbate 60 into the mixture, mixing the mixture with 50 parts by mass of the oil phase prepared in the step (2), grinding the mixture, and slowly adding 460 parts by mass of the water phase prepared in the step (3) into the mixture to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
Example 3
The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared according to the following steps:
(1) the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by mass: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of malaytea scurfpea fruit, 0.07 part of scorpion, 0.7 part of rhizoma drynariae and 0.7 part of prepared rhizome of rehmannia;
(2) pulverizing eucommia ulmoides, dragon's blood and fructus psoraleae into coarse powder, adding 95% ethanol as an entrainer, and infiltrating for 1 hour, wherein the volume ratio of the entrainer to the total mass of the eucommia ulmoides, the dragon's blood and the fructus psoraleae is 2 parts by volume: 1 part by mass of supercritical CO2Extracting, wherein the extraction process parameters are as follows: the extraction pressure is 28MPa, the extraction temperature is 55 ℃, and the extraction time is 150 minutes; recovering ethanol, collecting extractive solution, adding oleum Olivarum (LCT) 50 weight parts, heating to dissolve, and filtering to obtain oil phase;
(3) decocting the dregs of the decoction obtained in the step (2) with scorpion, rhizoma drynariae and prepared rhizome of rehmannia for three times, wherein the volume of water added in each decoction is 8 parts by volume of the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the rhizoma drynariae and the prepared rhizome of rehmannia: 1 part by mass, decocting for 1 hour, filtering, combining the filtrates, and concentrating to 460 parts by mass as a water phase for later use;
(4) taking 40 parts by mass of lauryl nitrogen
Adding 20075 parts by mass of polyethylene glycol into ketone, stirring to dissolve, adding 375 parts by mass of polysorbate 20, mixing with 50 parts by mass of the oil phase prepared in the step (2), homogenizing, and slowly adding(3) 460 parts by mass of the prepared water phase to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
Example 4
The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared according to the following steps:
(1) the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by mass: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of malaytea scurfpea fruit, 0.07 part of scorpion, 0.7 part of rhizoma drynariae and 0.7 part of prepared rhizome of rehmannia;
(2) extracting eucommia bark, dragon's blood and fructus psoraleae twice by using 70% ethanol in a refluxing way, wherein the ratio of the volume of the 70% ethanol added in each refluxing extraction to the total mass of the eucommia bark, the dragon's blood and the fructus psoraleae is 6 parts by volume: 1 part by mass, extracting for 2 hours under reflux, filtering, combining the filtrates obtained each time, recovering ethanol and concentrating to obtain clear paste, vacuum drying, pulverizing, adding fat-soluble solvent Ethyl Oleate (EO) to 100 parts by mass, heating to dissolve, filtering to obtain oil phase for use;
(3) decocting the dregs of the decoction obtained in the step (2) with scorpion, rhizoma drynariae and prepared rhizome of rehmannia twice, wherein the volume of water added in each decoction is 10 parts by volume of the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the rhizoma drynariae and the prepared rhizome of rehmannia: 1 part by mass, decocting for 2 hours, filtering, combining the filtrates, and concentrating to 460 parts by mass as a water phase for later use;
(4) taking 40 parts by mass of lauryl nitrogen
And (3) adding 125 parts by mass of propylene glycol into the ketone, stirring to dissolve the propylene glycol, adding 275 parts by mass of polyoxyethylene castor oil (Cremephor EL) into the mixture to be mixed with 100 parts by mass of the oil phase prepared in the step (2), grinding the mixture, and slowly adding 460 parts by mass of the water phase prepared in the step (3) into the mixture to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
Example 5
The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared according to the following steps:
(1) the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by mass: 0.42 part of eucommia bark, 0.07 part of dragon's blood, 0.25 part of malaytea scurfpea fruit, 0.07 part of scorpion, 0.7 part of rhizoma drynariae and 0.7 part of prepared rhizome of rehmannia;
(2) reflux-extracting Eucommiae cortex, sanguis Draxonis and fructus Psoraleae with 95% ethanol once, wherein the ratio of the volume of 95% ethanol added to the total mass of Eucommiae cortex, sanguis Draxonis and fructus Psoraleae is 12 parts by volume: 1 part by weight, extracting for 1 hour under reflux, filtering, mixing the filtrates each time, recovering ethanol, concentrating to obtain fluid extract, vacuum drying, pulverizing, adding Medium Chain Triglyceride (MCT) to 50 parts by weight, heating to dissolve, and filtering to obtain oil phase;
(3) decocting the dregs of the decoction obtained in the step (2) with scorpion, rhizoma drynariae and prepared rhizome of rehmannia for three times, wherein the volume of water added in each decoction is 8 parts by volume of the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the rhizoma drynariae and the prepared rhizome of rehmannia: 1 part by mass, decocting for 1 hour, filtering, combining the filtrates, and concentrating to 460 parts by mass as a water phase for later use;
(4) taking 40 parts by mass of lauryl nitrogen
And (3) adding 75 parts by mass of glycerol into the ketone, stirring to dissolve the glycerol, adding 375 parts by mass of polyoxyethylene hydrogenated castor oil (Cremephor RH40) into the mixture to be mixed with 50 parts by mass of the oil phase prepared in the step (2), grinding the mixture, and slowly adding 460 parts by mass of the water phase prepared in the step (3) into the mixture to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis.
Example 6: pharmacodynamic comparative study on external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis prepared in examples 1 to 5
(1) The influence of the externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis, which is prepared by the method of the embodiments 1 to 5, on the body-twisting reaction of mice with pain caused by acetic acid stimulation
A skin preparation
Taking SPF-grade NIH mice (with animal qualification number of 440709142, provided by Guangdong provincial medical experiment animal center), weighing 18-22 g, unhairing the abdomen of each group of mice with 8% sodium sulfide solution 24h before the experiment begins, wherein the unhairing area is about 2cm multiplied by 2cm, and the unhairing area is about 4cm2The hair removal should be done carefully and gently to avoid damage to the skin of the mice, after hair removal, the skin of the hair-removed area is washed gently with warm water, and after 24 hours, the skin of the hair-removed area is examined for damage. All mice in each group were warmed before being coated with the drugWashing the skin in the hair-removed area with water.
Grouping the animals:
the prepared mice were divided into 11 groups of 110 male and female halves at random by body weight, i.e., 10 mice each, i.e., the blank emulsion control group of example 1, the blank emulsion control group of example 2, the blank emulsion control group of example 3, the blank emulsion control group of example 4, the blank emulsion control group of example 5, the nataline emulsion group, the emulsion group of example 1, the emulsion group of example 2, the emulsion group of example 3, the emulsion group of example 4, and the emulsion group of example 5.
C dose setting
2, the emulsion of the sitagliptin: the pharmacodynamics experiment dosage of the nataline latex mouse is 0.78g kg-1And storing in a refrigerator at 4 ℃.
Examples 1-5 emulsions: examples 1-5 emulsion the pharmacodynamic experiment dose of mice was 0.194g crude drug/kg-1And storing in a refrigerator at 4 ℃.
Method of administering drug
After each group is coated with corresponding medicine outside according to the weight of a pressed object (the control group is coated with blank emulsion prepared according to the embodiment 1-5 with equal weight), non-irritant gauze is coated on the medicine coating part, the medical adhesive plaster is fixed by winding up and down for one circle, then the whole medicine coating area is fixed by back-to-back adhesive tape winding with corresponding area, the medicine is fully contacted with the skin of the animal within the medicine administration period, the medicine is continuously removed for 7 days 1 time every day, the medicine is removed after 6 hours every day, and the skin of the hair area is cleaned by warm water.
Method of measuring F
1h after the last administration of the drug at 7d, all groups of mice remove the drug or blank auxiliary materials, wash the abdomen with warm water, gently wipe the abdomen with sterile gauze, inject 0.7% glacial acetic acid 0.2 mL/mouse intraperitoneally, start timing, observe and count the latency(s) of writhing reaction of the mice within 20min after the glacial acetic acid injection and the writhing frequency of the mice within 20min (writhing reaction: the abdomen is sunken, the hind limbs are stretched, the buttocks is raised).
G experiment statistical method
All measurements are expressed as mean plus minus standard deviation (3^ s). The average numbers among the groups are compared by adopting One-way ANOVA (One-way ANOVA), the average numbers among the groups are compared pairwise, and an LSD-t method is adopted when the variance is uniform; when the variance is irregular, a Dunnett' sT3 method is adopted, and a histogram is drawn. Finished by SPSS15.0 software, a ═ 0.05. The counting data was checked by K-W rank-sum and two-by-two comparison by LSD-t test.
H result
Table 1 shows that the writhing latency is prolonged (P <0.05) and the writhing frequency is reduced (P <0.05) in mice of the emulsion groups of each example, compared with the corresponding blank emulsion control group.
TABLE 1 Effect of the emulsion groups of the examples on the pain response of mice induced by acetic acid stimulation
Note: p <0.05 compared to the blank control of the corresponding example
(2) The external traditional Chinese medicine emulsion prepared according to the method of the embodiment 1-5 for preventing and treating knee osteoarthritis has the influence on mouse auricle swelling caused by xylene
A skin preparation
Taking SPF-grade NIH mice (with animal qualification number of 440709142, provided by Guangdong provincial medical experiment animal center), weighing 18-22 g, unhairing the abdomen of each group of mice with 8% sodium sulfide solution 24h before the experiment begins, wherein the unhairing area is about 2cm multiplied by 2cm, and the unhairing area is about 4cm2The hair removal should be done carefully and gently to avoid damage to the skin of the mice, after hair removal, the skin of the hair-removed area is washed gently with warm water, and after 24 hours, the skin of the hair-removed area is examined for damage. Before each group of mice is coated with the medicine, the skin of the hair area is cleaned by warm water.
Grouping the animals:
the prepared mice were divided into 11 groups of 110 male and female halves at random by body weight, i.e., 10 mice each, i.e., the blank emulsion control group of example 1, the blank emulsion control group of example 2, the blank emulsion control group of example 3, the blank emulsion control group of example 4, the blank emulsion control group of example 5, the nataline emulsion group, the emulsion group of example 1, the emulsion group of example 2, the emulsion group of example 3, the emulsion group of example 4, and the emulsion group of example 5.
C dose setting
2, the emulsion of the sitagliptin: the pharmacodynamics experiment dosage of the nataline latex mouse is 0.78g kg-1And storing in a refrigerator at 4 ℃. Examples 1-5 emulsions: examples 1-5 emulsion the pharmacodynamic experiment dose of mice was 0.194g crude drug/kg-1And storing in a refrigerator at 4 ℃.
Method of administering drug
After each group is coated with corresponding medicine outside according to the weight of a pressed object (the control group is coated with blank emulsion prepared according to the embodiment 1-5 with equal weight), non-irritant gauze is coated on the medicine coating part, the medical adhesive plaster is fixed by winding up and down for one circle, then the whole medicine coating area is fixed by back-to-back adhesive tape winding with corresponding area, the medicine is fully contacted with the skin of the animal within the medicine administration period, the medicine is continuously removed for 7 days 1 time every day, the medicine is removed after 6 hours every day, and the skin of the hair area is cleaned by warm water.
Method of measuring F
1 hour after the last drug application, the drug or blank auxiliary materials were removed from each group of mice, the abdomen was washed with warm water, the mice were gently wiped with sterile gauze, the left ear was inflamed by 50 μ l of xylene, the mice were killed by pulling the neck after 1 hour, and the auricles were weighed from both ears to compare the auricle weight and the swelling rate (left ear weight-right ear weight/left ear weight).
G experiment statistical method
All measurements are expressed as mean square standard deviations. The data were not equally distributed, and comparisons between groups were examined by K-W, and pairwise comparisons were done by Dunnett's T3. And a histogram (Bar) is plotted. Finished by SPSS15.0 software, a ═ 0.05.
H result
Table 2 shows that the swelling rate of auricles of mice in the emulsion group prepared by the method described in each example is significantly reduced (P <0.01) compared to the control group.
TABLE 2 post-xylene-induced auricle swelling rates in mice
Note: p <0.01 in comparison with the blank control group of the corresponding example
Example 7
Clinical observation of the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis, prepared in the example 1, for treating knee osteoarthritis
General data: 90 cases were observed, and the patients with unilateral knee osteoarthritis were outpatient or hospitalized in our hospital, 27 men and 63 women. The age is 40-85 years, and the average age is 61.97 years. The course of the disease is 7d to 10 years, and the average is 3.45 years.
And (3) Western diagnosis: refer to the osteoarthritis diagnosis and treatment guidelines, which are made by the orthopedics division of the Chinese medical society in 2007:
① knee joint pain most of the time before the visit;
② X-ray film showing osteophyte formation at the edge of knee joint;
③ the joint fluid examination is in accordance with osteoarthritis;
④ age >40 years;
⑤ morning stiffness of knee joint <30 min;
⑥ the knee joint has friction sound when moving.
Knee osteoarthritis can be diagnosed when the condition is ① + ②, ① + ③ + ⑤ + ⑥ or ① + ④ + ⑤ + ⑥.
The traditional Chinese medicine syndrome diagnosis standard is as follows: the medicine is made according to the relevant contents of the national traditional Chinese medicine administration 'diagnosis and treatment standard of traditional Chinese medicine symptoms' and the higher medical college 'teaching material' traditional Chinese medicine osteopathia 'and the standard of curative effect of diagnosis of traditional Chinese medicine symptoms'.
① arthralgia due to wind-cold-dampness manifested by soreness and pain of limbs, severe pain, swelling of affected parts, joint movement, intolerance of wind-cold, and pain after heating, pale tongue with white greasy coating, and tense or soft pulse.
② stagnation of blood stasis can be manifested as stabbing pain of limbs and joints, fixed pain, local stiffness, or numbness, dark purple tongue with white coating.
③ deficiency of liver and kidney, manifested as hidden pain in knee joint, soreness and weakness of waist and knees, soreness and pain, red tongue with little coating, deep, thready and weak pulse.
Staging and grading standards: standing and setting the X-ray film according to a single leg, wherein the X-ray film comprises a positive side position of a knee joint and a shaft position sheet of a patella. Grading and grading according to the performance on the X-ray film.
A. Grading (K-L grading) the osteoarthritis was graded as per the Kellgren-Lawrence radiodiagnostic criteria and into five grades:
level 0: normal;
stage I: suspicious narrowing of the joint space, possibly osteophytes;
II stage: obvious osteophytes exist, and joint gaps are suspicious to narrow;
grade III: moderate osteophyte, obvious narrowing of joint space and changed sclerosing property;
stage IV: massive osteophytes, marked narrowing of the joint space, severe sclerosing lesions and marked deformities.
B. Staging
Early stage or early stage: osteophytes, sclerotic images, no narrowing of the joint space were visible (K-L1).
In the middle stage: the joint space is narrowed or disappeared (K-L2, 3).
At the end or late stage: wear or defect of the load surface of the cavity bone (K-L4).
Inclusion criteria were: the medical composition meets the Western medicine diagnosis standard, the traditional Chinese medicine syndrome diagnosis standard and Kellgren-Lawrence radiology classification, and belongs to the grade below grade III. The age is greater than 40 years.
Exclusion criteria: the age is less than 40 years old, pregnant or lactating women, allergic constitution or serious primary diseases such as cardiovascular disease, cerebrovascular disease, liver disease, kidney disease and hemopoietic system, and patients with psychosis or knee joint having history of fracture, dislocation, tuberculosis, tumor, infection, etc.
The grouping method comprises the following steps: the 90 patients who met the requirements were randomized into 2 groups of 45 patients using a random number method. I.e. the test group and the control group.
Observation indexes are as follows: and performing WOMAC scoring before and after treatment respectively, and comparing scoring change conditions. No difficulty 0; a minor proportion of 1; medium 2; very much 3; and an extreme 4. The total score minimum score was 0 and the total score maximum score was 96.
The treatment method comprises the following steps:
test group A: the emulsion composition prepared according to the method of example 1 is applied to the affected knee for external use, and is kneaded for 3 to 5 minutes, 2 to 3mL at a time, 2 times a day.
Control group B: the medicine is applied topically on affected parts, 1 tablet once and 1 time a day.
Treatment course C: the study was terminated 14 days, or upon reaching the clinical endpoint.
D clinical endpoint: WOMAC score 0, no swelling.
The statistical method comprises the following steps:
statistical software SPSS15.0 is used to process the data, and the differences between the groups after the improvement before and after the treatment of symptoms are analyzed by using a paired t test, wherein P <0.05 shows that the differences between the two groups of data have statistical significance. The measurement data of the abnormal distribution is expressed by median and quartile, and is counted by adopting a Wilcoxon method.
The difference between groups is judged by K-W test, and the statistical significance is realized when P is less than 0.05. The difference between the groups is shown, and the DunnettTS method is used for multiple comparisons, so that the difference of the treatment effect between the externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis and Tianhe Gutong is known.
Results of the study
A. General data: the study included 90 patients who were unilateral knee osteoarthritis, 27 men and 63 women. The age is 40-85 years, and the average age is 61.97 years. The course of the disease is 7d to 10 years, and the average is 3.45 years. The baseline was consistent between groups, no statistical difference, and comparable.
B. Clinical index comparison before and after treatment: after 14 days of treatment, the knee joint pain of the patients in the test group is improved compared with that of the control group. The results are shown in Table 3.
TABLE 3 comparison of pain scores before and after treatment
Injecting; compared with the pretreatment, # P <0.05
C. Comparison of stiffness before and after treatment: after 14 days of treatment, the knee stiffness scores of the patients in the test group were improved and improved compared with the control group. The results are shown in Table 4.
TABLE 4 comparison of stiffness scores before and after treatment
Injecting; compared with the pretreatment, # P <0.05
D. Comparing daily activity before and after treatment: after 14 days of treatment, compared with the control group, the knee joint daily activity degree scores of the patients in the test group are improved and improved. The results are shown in Table 5.
TABLE 5 comparison of daily Activity scores before and after treatment
F. Comparison of total score of WOMAC scores before and after treatment: after 14 days of treatment, compared with the control group, the knee joint daily activity degree scores of the patients in the test group are improved and improved. The results are shown in Table 6.
TABLE 6 comparison of WOMAC Total score before and after treatment
Note: compared with the pretreatment, # P <0.05
The results in tables 3 to 6 show that: the preparation is an effective preparation for preventing and treating knee osteoarthritis.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (4)
1. The externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is characterized by being an O/W type dispersion, and the average particle size of the dispersion is 0.5 micron; the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared by processing the following traditional Chinese medicinal materials in parts by weight: 0.42 part by mass of eucommia bark, 0.07 part by mass of dragon's blood, 0.25 part by mass of malaytea scurfpea fruit, 0.07 part by mass of scorpion, 0.7 part by mass of rhizoma drynariae and 0.7 part by mass of prepared rhizome of rehmannia; the externally applied traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis is prepared by the following steps:
(1) collecting Eucommiae cortex 0.42 weight parts, sanguis Draxonis 0.07 weight parts and fructus Psoraleae 0.25 weight parts, reflux-extracting with ethanol, concentrating the filtrate to fluid extract, or extracting the medicinal materials with supercritical CO2Extracting and collecting extract liquor; then vacuum drying the clear paste or extract, crushing, adding a fat-soluble solvent to 50-100 parts by mass, heating for dissolving, and filtering to obtain an oil phase; the fat-soluble solvent is at least one of isopropyl myristate, isopropyl palmitate, ethyl oleate, medium-chain triglyceride and olive oil; the ratio of the volume of the ethanol added in each reflux extraction to the total mass of the eucommia ulmoides, the dragon's blood and the fructus psoraleae is (6-12) parts by volume: 1 part by mass;
(2) taking the dregs of the decoction obtained in the step (1), 0.07 part by mass of scorpion, 0.7 part by mass of rhizoma drynariae and 0.7 part by mass of rehmannia glutinosa, decocting the mixture for 2-3 times with water, decocting the mixture for 1-2 hours each time, filtering the decoction, combining the filtrates, and concentrating the mixture to 460 parts by mass to obtain a water phase; the ratio of the volume of water added in each decoction to the total mass of the eucommia bark, the dragon's blood, the malaytea scurfpea fruit, the scorpion, the drynaria rhizome and the prepared rhizome of rehmannia is (8-10) parts by volume: 1 part by mass;
(3) mixing 40 parts by mass of a transdermal enhancer, 75-125 parts by mass of a cosurfactant and 275-375 parts by mass of a surfactant with 50-100 parts by mass of the oil phase prepared in the step (1), and adding 460 parts by mass of the water phase prepared in the step (2) under the condition of homogenizing or grinding to obtain the external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis; the surfactant is at least one of polysorbate 80, polysorbate 60, polysorbate 20, polyoxyethylene castor oil and polyoxyethylene hydrogenated castor oil; the cosurfactant is at least one of ethanol, isopropanol, polyethylene glycol 200, propylene glycol and glycerol; the transdermal enhancer is laurocapram
A ketone.
2. The external traditional Chinese medicine emulsion for preventing and treating knee osteoarthritis according to claim 1, wherein the ethanol reflux extraction process in the step (1) is as follows: extracting with ethanol under reflux for 2-4 times, wherein the reflux extraction time is 1-2 hours each time, filtering, combining the filtrates obtained each time, and concentrating to obtain fluid extract.
3. The topical Chinese medicinal emulsion for preventing and treating knee osteoarthritis according to claim 1, wherein the supercritical CO is adopted in step (1)2The extraction process comprises the following steps: pulverizing Eucommiae cortex, sanguis Draxonis and fructus Psoraleae into coarse powder, adding entrainer, soaking for 1 hr, and performing supercritical CO2Extracting and collecting extract liquor; wherein the ratio of the total mass of the eucommia bark, the dragon's blood and the psoralea fruit to the volume of the entrainer is 1 part by mass: (1-2) parts by volume.
4. The topical Chinese medicinal emulsion for preventing and treating knee osteoarthritis according to claim 3, wherein the supercritical CO is2The extraction pressure is 28MPa, the temperature is 55 ℃, and the extraction time is 150 minutes; the entrainer is 95% ethanol.
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