CN113797215B - Composition containing pinoresinol and cycloolivil 9-glycoside and preparation method and application thereof - Google Patents
Composition containing pinoresinol and cycloolivil 9-glycoside and preparation method and application thereof Download PDFInfo
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- CN113797215B CN113797215B CN202111013751.3A CN202111013751A CN113797215B CN 113797215 B CN113797215 B CN 113797215B CN 202111013751 A CN202111013751 A CN 202111013751A CN 113797215 B CN113797215 B CN 113797215B
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- parts
- glycoside
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- pinoresinol
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- HGXBRUKMWQGOIE-AFHBHXEDSA-N (+)-pinoresinol Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@@H]3[C@@H]([C@H](OC3)C=3C=C(OC)C(O)=CC=3)CO2)=C1 HGXBRUKMWQGOIE-AFHBHXEDSA-N 0.000 title claims abstract description 48
- OHOPKHNWLCMLSW-UHFFFAOYSA-N pinoresinol Natural products C1=C(O)C(OC)=CC(C2C3C(C(OC3)C=3C=C(CO)C(O)=CC=3)CO2)=C1 OHOPKHNWLCMLSW-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 235000007221 pinoresinol Nutrition 0.000 title claims abstract description 48
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Classifications
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- Veterinary Medicine (AREA)
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- Public Health (AREA)
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a composition containing pinoresinol and cyclopolybdenum-9-glycoside, and a preparation method and application thereof. The composition comprises the following components: cycloolivil 9-glycoside, chlorogenic acid, pinoresinol, eucommia ulmoides alcohol, and quercetin. The composition can effectively improve the effect of the composition on treating knee arthritis, and meanwhile, the utilization rate of the medicine is higher, so that the cost is effectively reduced, and meanwhile, the side effect of the medicine is reduced.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a composition containing pinoresinol and cyclopolybdenum-9-glycoside, and a preparation method and application thereof.
Background
Knee arthritis is a disorder based on degenerative pathological changes. The symptoms of the traditional Chinese medicine are red and sore knees, stair pain, and discomfort of knee pain when sitting and standing. Patients also show swelling, bouncing, hydrops and the like, and if the patients are not treated in time, joint deformity and disability can be caused. Joint diseases such as gonarthromeningitis, ligament injury, meniscus injury, knee joint dissociative body, popliteal cyst, patellar softening, goose foot bursitis, gonvarus/valgus and the like are also frequently caused at knee joint parts. The traditional medicines for treating knee osteoarthritis are various, for example, chinese patent application CN201910540161.2 provides a traditional Chinese medicine preparation for treating knee osteoarthritis, which comprises the following traditional Chinese medicine raw materials in parts by weight: 15-20 parts of eucommia ulmoides, 15-20 parts of epimedium herb, 5-10 parts of teasel root, 20-30 parts of medicinal cyathula root, 5-10 parts of malaytea scurfpea fruit, 15-20 parts of notopterygium root, 5-10 parts of bighead atractylodes rhizome, 15-20 parts of acanthopanax root, 10-20 parts of Chinese angelica, 2-5 parts of platycladi seed, 5-10 parts of cassia bark, 5-10 parts of lycopodium clavatum, 15-20 parts of curcuma zedoary, 5-10 parts of medlar, 5-10 parts of notopterygium root, 2-5 parts of liquorice, 5-10 parts of rhizoma atractylodis, 1-2 parts of wrinkled gianthyssop herb, 5-10 parts of root of red-rooted salvia, 10-20 parts of oyster, 10-20 parts of radix angelicae pubescentis, 2-5 parts of coix seed, 5-10 parts of papaya and 2-5 parts of smilax glabra. The preparation can effectively relieve pain of patients and can simultaneously increase bone density.
Chinese patent application CN201610170627.0 discloses a traditional Chinese medicine composition for treating knee arthritis, wherein the formula of the traditional Chinese medicine composition for treating knee arthritis is as follows: 12-18 parts of raw radix aconiti, 12-18 parts of raw kusnezoff monkshood root, 12-18 parts of manchurian wildginger, 12-18 parts of peach kernel, 12-18 parts of twotooth achyranthes root, 16-24 parts of incised notopterygium rhizome, 22-28 parts of common clubmoss herb, 22-28 parts of medicinal indianmulberry root, 22-28 parts of clematis root, 22-28 parts of garden balsam stem, 22-28 parts of rhubarb, 22-28 parts of szechuan lovage rhizome, 20-30 parts of Chinese angelica, 20-30 parts of suberect spatholobus stem, 20-30 parts of erythrina bark and 20-30 parts of mulberry twig. Has effects in dispelling pathogenic wind, removing dampness, promoting blood circulation, activating blood circulation, dredging meridian passage, relieving pain, promoting blood circulation, and relieving pain.
Most of the medicaments in the prior art are rich in raw materials, have a certain effect of relieving the knee arthritis, but do not effectively improve the utilization efficiency of the medicaments, the curative effect still needs to be improved, meanwhile, the interaction among the raw materials is ambiguous, and the side effect is great in the use process of patients.
The invention aims to provide a composition for treating knee arthritis, which can effectively improve the effect of the composition on treating knee arthritis, has higher utilization rate of medicines, and reduces side effects of the medicines while effectively reducing the cost.
Disclosure of Invention
In order to overcome the technical problems, the invention provides a composition containing pinoresinol and cyclopolybdarietin 9-glycoside, and a preparation method and application thereof. The composition has good effect of treating knee arthritis, and simultaneously, the utilization rate of the medicine is high, so that the cost is effectively reduced, and the side effect of the medicine is reduced.
In order to achieve the above object, the technical scheme provided by the invention is as follows:
a composition comprising a cyclic olivil 9-glycoside, comprising the following components: cycloolivil 9-glycoside, chlorogenic acid, pinoresinol, eucommia ulmoides alcohol, and quercetin.
Preferably, the composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 5-20 parts of cyclopolybdarietin 9-glucoside, 1-10 parts of chlorogenic acid, 5-15 parts of pinoresinol, 1-5 parts of eucommia ulmoides alcohol and 1-5 parts of quercetin.
Preferably, the composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 8-12 parts of cycloolivil 9-glucoside, 5-7 parts of chlorogenic acid, 7-11 parts of pinoresinol, 2-4 parts of eucommia ulmoides alcohol and 2-3 parts of quercetin.
Another object of the present invention is to provide a method for preparing the composition containing the cyclic olivil 9-glycoside, comprising the steps of:
(1) Adding a surfactant A into distilled water, heating, sequentially dissolving the 9-glucoside of the cycloolivil, chlorogenic acid and pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding a surfactant B into distilled water, and then adding eucommia ulmoides alcohol and quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
Preferably, in step (1), the surfactant a is any one or more of soybean lecithin, octyl- β -D-glucopyranoside, dodecyl- β -D-maltopyranoside, and N-dodecyl-N-methyl glucamide.
Preferably, in the step (1), the surfactant A is a mixture of N-dodecyl-N-methyl glucamide and soybean lecithin in a mass ratio of 4-6:1.
Preferably, the addition amount of the surfactant A is 0.1-0.5% of the mass of distilled water.
Preferably, the distilled water is added in an amount of 2-3 times the total mass of the 9-glycoside of the olivil, chlorogenic acid and pinoresinol.
Preferably, in step (1), the heating temperature is 30-45 ℃.
Preferably, the surfactant B is tea saponin, and the addition amount of the tea saponin is 0.1-1% of the total mass of the eucommia ulmoides alcohol and the quercetin.
Preferably, the preparation method of the tea saponin comprises the following steps:
pulverizing tea seed cake, soaking in hot water for extraction, filtering, treating the extractive solution with macroporous adsorbent resin, eluting with ethanol water solution, and drying to obtain tea saponin.
Preferably, the temperature of the hot water is 60-80 ℃, and the extraction time is 3-4h.
Preferably, sodium carbonate is added in the extraction process, wherein the addition amount of the sodium carbonate is 5-10% of the mass of the tea seed cake.
Preferably, the macroporous adsorption resin is D3520 or D4006 macroporous adsorption resin.
The specific process of eluting the ethanol water solution comprises eluting with 80-95% ethanol water solution to remove impurities, eluting with 30-45% ethanol, and collecting eluate.
Preferably, the elution rate of 80-95% by volume fraction is 1-3BV/h, and the amount is 1-2BV.
Preferably, the elution rate of 30-45% by volume is 1-3BV/h and the amount is 3-5BV.
The invention also aims to provide the application of the composition containing pinoresinol and the cyclophilin 9-glycoside in preparing the knee osteoarthritis medicine.
Another object of the present invention is to provide a formulation of the composition containing pinoresinol and cyclopolytin 9-glycoside, which is a granule, a tablet, a capsule or an oral liquid.
Compared with the prior art, the invention has the technical advantages that:
(1) The composition containing the pinoresinol and the 9-glucoside of the cyclopolyol has better effect of treating knee osteoarthritis and has better synergistic effect with chlorogenic acid, pinoresinol, eucommia ulmoides alcohol and quercetin.
(2) The surfactant is added in the process of preparing the composition, so that the storage stability of the composition can be improved, and the drug effect stability can be improved.
(3) According to the invention, the tea saponin is added in the preparation process, so that on one hand, the stability of the composition can be effectively promoted, and on the other hand, the tea saponin can also cooperate with eucommia ulmoides alcohol and quercetin to promote the drug effect of the composition.
Detailed Description
The present invention will be described by way of specific examples, to facilitate understanding and grasping of the technical solution of the present invention, but the present invention is not limited thereto. The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, are commercially available.
Example 1
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 12 parts of cyclopolybdarietin 9-glucoside, 7 parts of chlorogenic acid, 7 parts of pinoresinol, 4 parts of eucommia ulmoides alcohol and 2 parts of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2 times of the total mass of the cyclopolyartrin 9-glucoside, the chlorogenic acid and the pinoresinol, and adding 0.3 weight percent of distilled water into the distilled water, wherein the mass ratio is 5:1, heating the mixture of N-dodecyl-N-methyl glucamide and soybean lecithin to 40 ℃, sequentially dissolving the 9-glucoside of the cycloolivil, chlorogenic acid and pinoresinol into the mixture, and stirring the mixture to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.3wt% of the total mass of the eucommia ulmoides alcohol and the quercetin, and adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 70 ℃, adding sodium carbonate accounting for 6wt% of the mass of the tea seed cakes, soaking and extracting for 3 hours, filtering, treating an extracting solution by using D3520 macroporous absorbent resin, eluting by using an ethanol water solution with the volume fraction of 80% of 2BV to remove impurities, wherein the eluting rate is 2BV/h; eluting with ethanol with volume fraction of 35% of 4BV, and collecting eluate with elution rate of 2BV/h; and drying the eluent to obtain the tea saponin.
Example 2
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 5 parts of cyclopolybdarietin 9-glucoside, 5 parts of chlorogenic acid, 11 parts of pinoresinol, 2 parts of eucommia ulmoides alcohol and 1 part of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 3 times of the total mass of the cyclopolyartrin 9-glucoside, the chlorogenic acid and the pinoresinol, adding 0.5 weight percent of a mixture of N-dodecyl-N-methyl glucamide and soybean lecithin with the mass ratio of 4:1 into the distilled water, heating to 30 ℃, sequentially dissolving the cyclopolyartrin 9-glucoside, the chlorogenic acid and the pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.1% of the total mass of the eucommia ulmoides alcohol and the quercetin, and adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 60 ℃, adding sodium carbonate accounting for 5wt% of the mass of the tea seed cakes, soaking and extracting for 3 hours, filtering, treating an extracting solution by using D4006 macroporous adsorbent resin, eluting by using 1BV of ethanol water solution with the volume fraction of 95% to remove impurities, wherein the eluting rate is 1BV/h; eluting with 45% ethanol of 5BV at an elution rate of 1BV/h; and drying the eluent to obtain the tea saponin.
Example 3
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 20 parts of cyclopolybdarietin 9-glucoside, 10 parts of chlorogenic acid, 11 parts of pinoresinol, 5 parts of eucommia ulmoides alcohol and 5 parts of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2-3 times of the total mass of the cyclopolybdarietin 9-glucoside, the chlorogenic acid and the pinoresinol, adding 0.1 weight percent of a mixture of N-dodecyl-N-methyl glucamide and soybean lecithin with the mass ratio of 6:1 into the distilled water, heating to 45 ℃, sequentially dissolving the cyclopolybdarietin 9-glucoside, the chlorogenic acid and the pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 1% of the total mass of the eucommia ulmoides alcohol and the quercetin, and then adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 80 ℃, adding sodium carbonate accounting for 10wt% of the mass of the tea seed cakes, soaking and extracting for 4 hours, filtering, treating an extracting solution by using D4006 macroporous adsorbent resin, eluting by using ethanol water solution with the volume fraction of 80% of 2BV to remove impurities, wherein the eluting rate is 3BV/h; eluting with ethanol with volume fraction of 3BV of 30%, and collecting eluate with elution rate of 3BV/h; and drying the eluent to obtain the tea saponin.
Example 4
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 12 parts of cyclopolybdarietin 9-glucoside, 7 parts of chlorogenic acid, 7 parts of pinoresinol, 4 parts of eucommia ulmoides alcohol and 2 parts of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2 times of the total mass of the 9-glucoside of the cycloolivil, the chlorogenic acid and the pinoresinol, adding 0.3 weight percent of soybean lecithin into the distilled water, heating to 40 ℃, sequentially dissolving the 9-glucoside of the cycloolivil, the chlorogenic acid and the pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.3wt% of the total mass of the eucommia ulmoides alcohol and the quercetin, and adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 70 ℃, adding sodium carbonate accounting for 6wt% of the mass of the tea seed cakes, soaking and extracting for 3 hours, filtering, treating an extracting solution by using D3520 macroporous absorbent resin, eluting by using an ethanol water solution with the volume fraction of 80% of 2BV to remove impurities, wherein the eluting rate is 2BV/h; eluting with ethanol with volume fraction of 35% of 4BV, and collecting eluate with elution rate of 2BV/h; and drying the eluent to obtain the tea saponin.
Example 5
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 12 parts of cyclopolybdarietin 9-glucoside, 7 parts of chlorogenic acid, 7 parts of pinoresinol, 4 parts of eucommia ulmoides alcohol and 2 parts of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2 times of the total mass of the 9-glucoside of the cycloolivil, the chlorogenic acid and the pinoresinol, adding 0.3 weight percent of dodecyl-beta-D-maltopyranoside into the distilled water, heating to 40 ℃, sequentially dissolving the 9-glucoside of the cycloolivil, the chlorogenic acid and the pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.3wt% of the total mass of the eucommia ulmoides alcohol and the quercetin, and adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 70 ℃, adding sodium carbonate accounting for 6wt% of the mass of the tea seed cakes, soaking and extracting for 3 hours, filtering, treating an extracting solution by using D3520 macroporous absorbent resin, eluting by using an ethanol water solution with the volume fraction of 80% of 2BV to remove impurities, wherein the eluting rate is 2BV/h; eluting with ethanol with volume fraction of 35% of 4BV, and collecting eluate with elution rate of 2BV/h; and drying the eluent to obtain the tea saponin.
Comparative example 1
The difference compared to example 1 is that eucommia ulmoides alcohol is used instead of quercetin.
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 12 parts of cyclopolybdarietin 9-glucoside, 7 parts of chlorogenic acid, 7 parts of pinoresinol and 6 parts of eucommia ulmoides alcohol.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2 times of the total mass of the cyclopolyartrin 9-glucoside, the chlorogenic acid and the pinoresinol, and adding 0.3 weight percent of distilled water into the distilled water, wherein the mass ratio is 5:1, heating the mixture of N-dodecyl-N-methyl glucamide and soybean lecithin to 40 ℃, sequentially dissolving the 9-glucoside of the cycloolivil, chlorogenic acid and pinoresinol into the mixture, and stirring the mixture to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.3wt% of the total mass of eucommia ulmoides alcohol, and adding the eucommia ulmoides alcohol to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin is the same as that of the example 1.
Comparative example 2
The difference compared to example 1 is that citric acid is used instead of chlorogenic acid.
The composition containing the cyclopolyartarin 9-glycoside comprises the following components in parts by weight: 12 parts of cyclopolybdarietin 9-glucoside, 7 parts of citric acid, 7 parts of pinoresinol, 4 parts of eucommia ulmoides alcohol and 2 parts of quercetin.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) Taking distilled water which is 2 times of the total mass of the cyclopolyartrin 9-glucoside, the citric acid and the pinoresinol, and adding 0.3 weight percent of distilled water into the distilled water, wherein the mass ratio is 5:1, heating the mixture of N-dodecyl-N-methyl glucamide and soybean lecithin to 40 ℃, sequentially dissolving the 9-glucoside of the cycloolivil, the citric acid and the pinoresinol into the mixture, and stirring the mixture to form a solution 1;
(2) Adding tea saponin into distilled water, wherein the adding amount of the tea saponin is 0.3wt% of the total mass of the eucommia ulmoides alcohol and the quercetin, and adding the eucommia ulmoides alcohol and the quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring to obtain the composition containing pinoresinol and the 9-glucoside of the cycloolivil.
The preparation method of the tea saponin comprises the following steps: crushing tea seed cakes, adding the crushed tea seed cakes into hot water at 70 ℃, adding sodium carbonate accounting for 6wt% of the mass of the tea seed cakes, soaking and extracting for 3 hours, filtering, treating an extracting solution by using D3520 macroporous absorbent resin, eluting by using an ethanol water solution with the volume fraction of 80% of 2BV to remove impurities, wherein the eluting rate is 2BV/h; eluting with ethanol with volume fraction of 35% of 4BV, and collecting eluate with elution rate of 2BV/h; and drying the eluent to obtain the tea saponin.
Comparative example 3
The difference compared with example 1 is that the preparation method of tea saponin is different.
A composition containing 9-glycoside of Cycloolivil comprises the same components as in example 1.
The preparation method of the composition containing the cyclopolyartrin 9-glycoside comprises the following steps:
(1) - (3) the same as in example 1.
The preparation method of the tea saponin comprises the following steps:
pulverizing tea seed cake, soaking in 70deg.C hot water for 3 hr, filtering, treating the extractive solution with D3520 macroporous adsorbent resin, eluting with 2BV 90% ethanol water solution at an elution rate of 2 BV/hr, eluting with 4BV 40% ethanol at an elution rate of 2 BV/hr, eluting, collecting eluate, and drying to obtain tea saponin.
1. Experimental experiment of anti-inflammatory action of auricle swelling of rat caused by xylene
SPF-class healthy male Wistar rats were divided into 10 groups of 200+ -20 g, each group of 6 animals, which were blank group, positive drug group, examples 1-5 group, and comparative examples 1-3 group, respectively. The right ear of each rat was coated with xylene, 50 ul/mouse, and 30min later administered in the following groups: the blank group was not given any drug; examples 1-5 and comparative examples 1-3 were given the compositions prepared in the respective groups at an effective level of 0.5mg/kg, respectively, and after application to the right ears of rats, the compositions were massaged appropriately to promote drug absorption; the positive drug group uses commercial loxoprofen sodium gel paste (Hunan Jiudian pharmacy), and the right ear of the rat is coated on both sides to be properly massaged to promote drug absorption. After 1h, animals were sacrificed from cervical dislocation, round lugs were respectively punched on the same parts of the two ears by a 6mm diameter puncher, the mass was weighed by a precision torsion balance, and the swelling degree and swelling rate were calculated, and the results are shown in Table 1.
Table 1 swelling degree and swelling Rate data
In the same list, different symbols have significant differences, and P is less than 0.05.
As can be seen from Table 1, the compositions provided in the examples 1-5 and comparative examples 1-3 reduced the swelling of the auricles of rats due to xylene, which demonstrates that the compositions provided by the present invention have a better anti-inflammatory effect, as compared to the blank. Meanwhile, the raw material composition and the preparation method of the composition have great influence on the effect.
2. Model experiment of knee osteoarthritis in rats
60 SD rats were selected, and the weight of the rats was 200.+ -.20 g, and the rats were randomly divided into 10 groups of 6 rats each, which were respectively a normal group, a model group, examples 1-5 groups, and comparative examples-3 groups.
Except for normal groups, rats were injected with papain into the joint cavity to replicate KOA model; the rats were treated with skin preparation and disinfection, the right forelimb knee joint parts and the hairs below were shaved off, and after skin disinfection with 75% ethanol, the right forelimb knee joint cavity was injected with 0.2mL of 4% papain solution once every 2d for 2 weeks. After 14d, the following symptoms were found in the rats, indicating successful replication: redness, swelling, fever and pain of the knee joint on the right front side, with swelling of soft tissues or hydrops; stiffness and limited mobility in the right anterior knee joint and surrounding; the pathological examination result of the knee joint at the right front side shows that a large amount of exudates appear in the joint cavity; the cartilage surface is not smooth, and there are arthritis pathological changes such as synovial hyperplasia or adhesion. On day 2 after successful molding, rats of each of the groups 1 to 5 and comparative examples 1 to 3 were subjected to respective groups of prepared compositions except for the normal group and the model group which were subjected to gastric lavage with physiological saline, and the rats of each group were subjected to gastric lavage at a dose of 10mg/kg/d for intervention, and femoral arterial blood was collected from each group of rats after 4 weeks of intervention at 1500 rpm.min -1 Centrifuging for 10min, collecting serum, and detecting IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and IL-1β (interleukin-1β) levels by enzyme-linked immunosorbent assay (enzyme-linked immunosorbent assay kit manufacturer: wohman Irett biosciences). The results are shown in Table 2.
TABLE 2 inflammatory factor levels
Test group | IL-6(ng·L -1 ) | TNF-α(ng·L -1 ) | IL-1β(ng·L -1 ) |
Blank group | 18.32±2.37 a | 22.15±6.14 f | 6.01±1.09* |
Model group | 44.26±4.51 b | 41.34±4.11 g | 12.65±2.34 # |
Example 1 | 23.57±5.34 c | 25.43±3.57 h | 7.46±0.87 △ |
Example 2 | 24.61±3.08 c | 25.69±8.21 h | 7.29±1.54 △ |
Example 3 | 23.68±1.55 c | 26.07±6.47 h | 7.54±2.05 △ |
Example 4 | 30.25±2.67 d | 28.34±5.22 h | 8.02±3.11 ▼ |
Example 5 | 31.08±3.26 d | 29.10±4.28 h | 8.71±2.62 ▼ |
Comparative example 1 | 34.53±6.64 e | 33.76±9.14 i | 10.89±1.03 ◇ |
Comparative example 2 | 37.28±4.09 e | 36.21±5.67 i | 11.32±5.43 ◇ |
Comparative example 3 | 33.56±5.12 e | 31.43±4.39 i | 9.86±2.19 ◇ |
In the same list, different letters or symbols have significant differences, and P is less than 0.05.
As can be seen from Table 2, the compositions provided in the examples 1-5 and comparative examples 1-3 effectively interfere with serum inflammatory factor levels, compared to the blank, demonstrating that the compositions provided in the present invention have better effect in treating knee osteoarthritis. Meanwhile, the raw material composition and the preparation method of the composition have great influence on the effect.
The foregoing detailed description is directed to one of the possible embodiments of the present invention, which is not intended to limit the scope of the invention, but is to be accorded the full scope of all such equivalents and modifications so as not to depart from the scope of the invention.
Claims (12)
1. The composition containing the cyclopolyartarin 9-glycoside is characterized by comprising the following active ingredients in parts by weight: 5-20 parts of cyclopolybdarietin 9-glucoside, 1-10 parts of chlorogenic acid, 5-15 parts of pinoresinol, 1-5 parts of eucommia ulmoides alcohol and 1-5 parts of quercetin; the composition containing the cyclopolyartrin 9-glycoside also needs to be added with a surfactant in the preparation process, wherein the surfactant comprises tea saponin, and the preparation method of the tea saponin comprises the following steps: pulverizing tea seed cake, soaking in hot water, extracting, adding sodium carbonate, filtering, treating the extractive solution with macroporous adsorbent resin, eluting with ethanol water solution, and drying to obtain tea saponin.
2. The composition containing the cyclopolyolivil 9-glycoside according to claim 1, wherein the active ingredient consists of the following components in parts by weight: 8-12 parts of cycloolivil 9-glucoside, 5-7 parts of chlorogenic acid, 7-11 parts of pinoresinol, 2-4 parts of eucommia ulmoides alcohol and 2-3 parts of quercetin.
3. Process for the preparation of a composition comprising a cyclic olivil 9-glycoside according to any one of claims 1 to 2, characterized in that it comprises the following steps:
(1) Adding a surfactant A into distilled water, heating, sequentially dissolving the 9-glucoside of the cycloolivil, chlorogenic acid and pinoresinol into the distilled water, and stirring to form a solution 1;
(2) Adding a surfactant B into distilled water, and then adding eucommia ulmoides alcohol and quercetin to form a solution 2;
(3) Mixing the solution 1 and the solution 2, and stirring.
4. A process for the preparation of a composition comprising a cyclic olivil 9-glycoside according to claim 3, wherein in step (1), the surfactant a is any one or more of soybean lecithin, octyl- β -D-glucopyranoside, dodecyl- β -D-maltopyranoside and N-dodecyl-N-methyl glucamide; the addition amount of the surfactant A is 0.1-0.5% of the mass of distilled water; the addition amount of the distilled water is 2-3 times of the total mass of the 9-glucoside of the cyclopolybdarietin, the chlorogenic acid and the pinoresinol.
5. The method for preparing a composition containing cyclopolyolivil 9-glycoside according to claim 4, wherein in the step (1), the surfactant A is a mixture of N-dodecyl-N-methyl glucamide and soybean lecithin in a mass ratio of 4-6:1.
6. The method for preparing the composition containing the cyclopolyartarin 9-glycoside according to claim 3, wherein the surfactant B is tea saponin, and the addition amount of the tea saponin is 0.1-1% of the total mass of the eucommia ulmoides alcohol and the quercetin.
7. The method for preparing the composition containing the cyclopolybdenum-phenyl-amine 9-glycoside according to claim 6, wherein the method for preparing the tea saponin comprises the following steps: pulverizing tea seed cake, soaking in hot water for extraction, filtering, treating the extractive solution with macroporous adsorbent resin, eluting with ethanol water solution, and drying to obtain tea saponin.
8. The method for preparing a composition containing cyclopolyartocarpin 9-glycoside according to claim 7, wherein sodium carbonate is added during the extraction process, and the addition amount of sodium carbonate is 5-10% of the mass of the tea seed cake.
9. The method for preparing a composition containing cyclopolyolivil 9-glycoside according to claim 7, wherein the macroporous adsorbent resin is D3520 or D4006 type macroporous adsorbent resin.
10. The method for preparing the composition containing the cyclopolyolivil 9-glycoside according to claim 7, wherein the ethanol aqueous solution is eluted by eluting with 80-95% ethanol aqueous solution by volume fraction, eluting with 30-45% ethanol, and collecting the eluate.
11. Use of a composition comprising a cyclic olivil 9-glycoside according to any one of claims 1-2 or a composition comprising a cyclic olivil 9-glycoside prepared by the method of any one of claims 3-10 for the preparation of a medicament for treating knee osteoarthritis.
12. A formulation of a composition comprising a cyclic olivil 9-glycoside according to any one of claims 1-2 or a composition comprising a cyclic olivil 9-glycoside prepared by the method of any one of claims 3-10, wherein the formulation is a granule, tablet, capsule or oral liquid.
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