CN1264536C - Anti-gout composition and preparing process thereof - Google Patents
Anti-gout composition and preparing process thereof Download PDFInfo
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- CN1264536C CN1264536C CN02138216.6A CN02138216A CN1264536C CN 1264536 C CN1264536 C CN 1264536C CN 02138216 A CN02138216 A CN 02138216A CN 1264536 C CN1264536 C CN 1264536C
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- ramulus cinnamomi
- volatile oil
- cacumen platycladi
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Abstract
The present invention relates to a composition which comprises at least two components of the volatile oil of cassia twig, total flavonoids of oriental arborvitae and total alkaloids of hemlock parsley, wherein the composition contains 0.1 to 0.4g of volatile oil of cassia twig, 0.5 to 2.0g of total flavonoids of oriental arborvitae, and 0.4 to 1.6g of total alkaloids of hemlock parsley. The composition can be used for medicines and health foods for preparing, preventing and treating hyperuricemia and gout, and the present invention has the advantages of stable, safe and reliable treating effects.
Description
One, technical field:
The present invention relates to the composition and method of making the same and the medicinal usage of active ingredient of natural plant, particularly relate to Ramulus Cinnamomi Volatile oil, Cacumen Platycladi total flavones and (or) Rhizoma Chuanxiong total alkaloids is prepared into the medicine of treatment or prevention hyperuricemia and gout.
Two, background technology:
Gout is the disease that a kind of purine metabolic disturbance causes.Clinical characters is hyperuricemia, gouty arthritis, joint deformity, nephropathy and urate calculus, the formation of gout calculus etc.Wherein hyperuricemia is the paranormal a kind of state of uric acid in the blood, is a stage in the gout evolution; Gouty arthritis is after serum uric acid level increases, and urate deposition stimulates the joint and causes a series of inflammatory reaction at joint tissue.The gout symptom is based on joint of the lower extremity red and swollen heat pain repeatedly, on differential diagnosis in tcm belongs to damp and hot numbness category more.Its pathogenesis or because of the natural endowment deficiency, or because of the eating and drinking without temperance day after tomorrow, visceral dysfunction, distinguish not turbid not normal, so wet, heat, the stasis of blood, the life thereupon of turbid all diseases.
Existing Western medicine is treated at the symptom selectivity that different times showed at patient with gout.Be used for gout acute attack treatment as anti-inflammation analgesis medicament colchicine and indometacin, drainage uric acid medicine such as probenecid, benzbromarone are used for gap phase and chronic phase treatment, and it is synthetic that xanthine oxidase inhibitor medicine allopurinol (unique use clinically) suppresses uric acid.But the said medicine toxic and side effects is big, and the patient often can not adhere to taking for a long time, so that the wayward state of an illness.Have the GI irritation effect as colchicine and indometacin, the former also produces leucocytes reduction and alopecia etc.; Probenecid, benzbromarone have gastrointestinal reaction, renal colic and excite side effect such as gout acute attack; Allopurinol causes allergy (incidence rate is up to 10-15%), super quick Stevena-Johnson syndrome (can cause 27.5% the maculopapule death occurs), bone marrow depression serious toxic and side effects such as (though more rare, consequence are serious).
The Chinese medicine gout can be carried out dialectical executing according to different etiology and pathogenesis and be controlled.Damp-heat type is controlled to let out turbid heat clearing away collateral dredging, and Fang Duoyong adds the flavor ermiao san.Cold-dampness type is controlled with warm cold expelling wet, and expelling wind and removing dampness is main, and the side selects Aconitum carmichjaelii Debx. to fry in shallow oil, and closes red soup of Semen Coicis or Candle-sticks numbness soup, Cock Crowing.Intermingling cold and heat is double to be controlled based on expelling wind and removing dampness, vital energy regualting and blood circulation-promoting, softening and eliminating sputum, with Herba Ephedrae Fructus Forsythiae, Semen Phaseoli Tonga flavor accumulate heat-transformation of a specified duration to control anemofrigid-damp arthralgia, exopathogen also exists.The obstruction of collaterals by blood stasis type is controlled with nourshing blood and promoting blood circulation, and the removing blood stasis collateral dredging is main, and it is red etc. that the side adds Ramulus Mori, the Radix Polygoni Multiflori, Radix Achyranthis Bidentatae, Semen Coicis with Traditional Chinese medicine decoction for treating-ache and expelling atagnate plus-minus or SIWU TANG, or select for use Radix Salviae Miltiorrhizae, Caulis Spatholobi, Herba Lycopi, Flos Carthami, Rhizoma Chuanxiong with blood circulation promoting and blood stasis dispelling.Type of obstruction of phlegm and blood stasis is controlled based on eliminate stagnation and dissolve phlegm, is searched evil collateral dredging, selects Squama Manis, Eupolyphaga Seu Steleophaga, Zaocys, Scolopendra, Radix Stephaniae Tetrandrae, Radix Clematidis, Pheretima etc. for use.Insufficiency of the spleen damp-obstruction type is controlled with invigorating the spleen and benefiting QIization turbid, and it is main letting out turbid collateral dredging, and the side subtracts with raising splenoyang to strengthen stomach Tonga, or selects for use the Radix Astragali, Radix Angelicae Sinensis, Bi , Radix Achyranthis Bidentatae, Flos Carthami, the Rhizoma Atractylodis Macrocephalae, Semen Coicis red etc.
Ramulus Cinnamomi is the twig of canella Cortex Cinnamomi cinnamomum cassia Presl, but expelling cold and relieving exterior syndrome, promoting the flow of QI-blood by warming the meridian, clinical treatment rheumatic Bi syndrome, apoplexy, children's's myocarditis and the gynaecopathia etc. of being mainly used in; Ramulus Cinnamomi is rich in volatile oil, and cinnamic aldehyde is its main component, reaches 62.4%, has calmness, analgesia, refrigeration function.Cacumen Platycladi is twig and the leaf of Cupressaceae plant Cacumen Platycladi Platycladus orientalis (L.) Franco., and clearing away heat and cooling blood is controlled damp and hot arthralgia pain, clinically is usually used in treating pulmonary tuberculosis, pertussis etc.; Cacumen Platycladi mainly contains flavone, tannin and volatilization wet goods, and the rough general flavone content of fresh Cacumen Platycladi is 1.72%, is mainly compositions such as Quercetin.Rhizoma Chuanxiong is a samphire Rhizoma Chuanxiong Ligusticum chuanxiong Hort. rhizome, blood-activating and qi-promoting, the wind pain relieving of loosing.Rhizoma Chuanxiong contains volatile oil, alkaloid, phenolic constituent, lactone and ferulic acid etc., alkaloid is higher, have effects such as blood circulation promoting and blood stasis dispelling, anti-platelet aggregation, blood vessel dilating, free radical resisting, diuresis from isolated ligustrazine wherein, clinical treatment cardiovascular and cerebrovascular disease, pulmonary heart disease chronic nephropathy and the hepatopathy etc. of being widely used in.
Three, summary of the invention:
1. goal of the invention
Purpose of the present invention is exactly in order to address the above problem, and a kind of extract or pharmaceutical composition that is prepared into by two kinds of extracts wherein and preparation method thereof by Ramulus Cinnamomi, Cacumen Platycladi and Rhizoma Chuanxiong and the application in preparation prevention or treatment hyperuricemia and gout be provided.
2. technical scheme
Pharmaceutical composition of the present invention is characterized in that it is made by the active component of the plant extract of following weight proportion: Ramulus Cinnamomi Volatile oil 0.1-0.4g, Cacumen Platycladi total flavones 0.5-2.0g, Rhizoma Chuanxiong total alkaloids 0.4-1.6g; Perhaps by Ramulus Cinnamomi Volatile oil 0.1-0.4g, Cacumen Platycladi total flavones 0.5-2.0g; The preferable amount of said extracted thing active component is Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g, Rhizoma Chuanxiong total alkaloids 0.8g.
After each component is mixed can with the beta-schardinger dextrin-mixed in equal amounts, to increase the stability of compositions component.The consumption of beta-schardinger dextrin-also can change in proper range as the case may be.
Preparation of drug combination method of the present invention the steps include:
(1) Ramulus Cinnamomi supercritical CO
2Extraction, Petroleum ether extraction, vapor extraction or water boiling and extraction obtain Ramulus Cinnamomi Volatile oil;
(2) Cacumen Platycladi is extracted through the 0-95% ethanol water and obtains the Cacumen Platycladi total flavones;
(3) Rhizoma Chuanxiong obtains Rhizoma Chuanxiong total alkaloids through water or sour water-organic solvent, alcohol-sour water-organic solvent, alkalization-organic solvent, ion exchange resin or vapor extraction;
(4), promptly get compositions GCX with fully mixing behind the beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil with Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g, Rhizoma Chuanxiong total alkaloids 0.8g; Perhaps, promptly get compositions GC with fully mixing behind the beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil with Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g.
To add an amount of adjuvant among above-mentioned compositions GCX, the GC respectively, the preparation method with conventional can be made into solid orally ingestibles such as tablet, granule and capsule; Used adjuvant is the auxiliary agent of conventional usefulness, for example starch, gelatin, arabic gum, Silicon stone, Polyethylene Glycol.
Pharmaceutical composition of the present invention is used for preparing the application of the medicine for the treatment of hyperuricemia and gout.
3。Beneficial effect
The invention has the advantages that pharmaceutical composition of the present invention is to be main effective ingredient with Ramulus Cinnamomi Volatile oil, Cacumen Platycladi total flavones and Rhizoma Chuanxiong total alkaloids, combination is rationally succinct, and active ingredient is clear and definite, and therapeutic effect is remarkable; And the source of medical herbs is wide, and preparation technology is simple, is easy to realize industrial scale production.And can use compositions such as cinnamic aldehyde, Quercetin and ligustrazine respectively as quality control index.
Four, the specific embodiment:
The composition of embodiment 1 antigout drug compositions
A kind of antigout drug compositions is made up of Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g and Rhizoma Chuanxiong total alkaloids 0.8g; Perhaps formed by Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g.
Embodiment 2. anti-gout drugs preparation of compositions methods, its method step is:
(1) Ramulus Cinnamomi gets Ramulus Cinnamomi Volatile oil with vapor extraction, and yield is 1.2%, wherein contains cinnamic aldehyde 62.4%;
(2) Cacumen Platycladi is with 50% ethanol water hot reflux 4h of 20 times of volumes, and the extracting solution evaporate to dryness promptly gets the Cacumen Platycladi total flavones, and yield is 1.1%, wherein contains Quercetin 13.5%;
(3) Rhizoma Chuanxiong with acid extraction after, with lime water alkalization, alkaline solution gets Rhizoma Chuanxiong total alkaloids with ethyl acetate extraction again, yield is 1.4%, wherein ligustrazine is 20%.
(4) get Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g and Rhizoma Chuanxiong total alkaloids 0.8g,, promptly get compositions GCX with mixing behind the beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil; Perhaps get Ramulus Cinnamomi Volatile oil 0.2g and Cacumen Platycladi total flavones 1.0g,, promptly get compositions GC with mixing behind the beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil.
Embodiment 3. compositionss cause that to hyperuricemia and normal mouse serum uric acid level, xanthine oxidase and hypoxanthine oxidase activity, rat uric acid sodium gouty arthritis tissue and carrageenin cause the influence of arthroncus
Male mice in kunming, body weight 24 ± 2g, random packet, every day, i.g. was administered once, continuous four days, wherein normal saline group and hyperuricemia model are blank organizes every day all by 100ml/kg dosage i.g normal saline, and the blank group of each hyperuricemia model is at preceding 2 hours ip oxonic acid potassium salt of blood sampling, and the administration model group is last hour ip oxonic acid of administration potassium salt the last time.Last administration from animal eye socket rear vein beard rice blood, was measured serum uric acid level after 2 hours.
Male mice in kunming, body weight 24 ± 2g, random packet, every day, i.g. was administered once, and continuous 7 days, put to death animal, get liver and measure hypoxanthine oxidase (XDH) and xanthine oxidase (XO) vigor.
Male Wistar rat, body weight 200 ± 25g, random packet.Every day, i.g. was administered once, and continuous 7 days, and cause scorching modeling with uric acid sodium in preceding 1 hour of administration in the 4th day, measure the ankle swelling in rat degree after 72 hours.Or 24h puts to death after the modeling, gets and is tried periarticular soft tissues, measures K
+, 5-HT, NA and DA content.
Male SD rat, body weight 200-250g, random packet, the difference gastric infusion, 1h after the administration will cause inflammation under the right back toes aponeurosis (aponeuroses) of 1% carrageenin 0.1ml injection rat, observe the swelling degree that the naked joint of each Mus causes inflammation back 1h, 2h, 4h and 6h with the volumetric measurement method.
Compositions GCX, GC, GX see Table 1 and table 2 respectively to the result that influences of hyperuricemia and normal mouse serum uric acid level.Under this experiment condition, GCX, GC, GX all reduce hyperuricemia mice serum uric acid level significantly; Wherein GCX can return to hyperuricemia mice serum uric acid level normally, and action intensity is close with the positive drug allopurinol.Compositions GCX, GC, GX do not have the significance influence to normal mice serum uric acid level, and the allopurinol group can reduce the normal mouse serum uric acid level significantly.
Compositions GCX can significantly suppress the activity of mouse liver hypoxanthine oxidase (XDH) and xanthine oxidase (XO), and its effect is weaker than allopurinol (data see Table 3).
Compositions GCX causes that to rat uric acid sodium the influence of gouty arthritis model the results are shown in Table 4.Data show, GCX suppresses the rat gouty arthritis swelling that uric acid sodium causes significantly,, act on suitable with colchicine.Tried periarticular soft tissues Histological research and show, GCX and colchicine group all can be protected the inflammation tissue.GCX can reduce K in the inflammation tissue significantly
+Content (P＜0.001) and 5-HT content, action intensity and colchicine are suitable, do not influence (data slightly) but the content that is tried NE in the periarticular soft tissues, DA is had significance.
Compositions GCX the results are shown in Table 5 to the influence that rat carrageenan causes the toes swelling that inflammation causes.Data show, GCX can significantly suppress the foot swelling that carrageenin causes, reduces the swelling rate, and is suitable with the effect of positive drug meticorten.
Table 1 compositions GCX, GC, GX are to the influence of hyperuricemia mice serum uric acid level (x ± s)
| Group | Dosage (mg/kg) | Mice serum uric acid level (mg/100ml) |
| The blank group of normal saline group model GCX group GC group GX group purine alcohol group | - - 300 200 160 10 | 7.87±0.17 12.68±0.28 7.69±0.11 *** 8.72±0.16 ** 8.62±0.10 *** 7.46±0.17 *** |
Compare with the blank group of model:
*P＜0.05,
*P＜0.01,
* *P＜0.005
Table 2 compositions GCX is to the influence of normal mice serum uric acid level (x ± s)
| Group | Dosage (mg/kg) | Mice serum uric acid level (mg/100ml) |
| Normal saline group GCX group purine alcohol group | - 147 210 300 10 | 3.52±0.12 3.45±0.19 3.57±0.15 2.99±0.17 1.89±0.15 *** |
Compare with the normal saline group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
Table 3 compositions GCX is to the influence of mouse liver hypoxanthine oxidase (XDH) and xanthine oxidase (XO)
| Group | Dosage (mg/kg) | XDH | XO | The % suppression ratio | |
| (nmol uric acid/mmg prot， x±s) | XDH | XO | |||
| Normal saline group GCX group purine alcohol group | - 300 10 | 2.45±0.13 1.79±0.13 * 1.35±0.11 * | 2.26±0.08 1.81±0.11 * 1.34±0.04 * | - 26.9 44.9 | 19.9 40.7 |
Compare with the normal saline group:
*P＜0.001
Table 4 compositions GCX causes the influence (x ± s) of gouty arthritis inflammation tissue to rat uric acid sodium
| Dosage (mg/kg) | Ankle joint Zhou Jing (cm) | K +Content (mol/mg) | 5-HT content (g/g) | |
| The blank group of normal saline group model GCX group colchicine group | - - 300 12.5 | 2.24±0.08 3.17±0.12 2.76±0.09 2.56±0.14 | 2.10±0.02 7.42±0.06 3.02±0.04 * 3.72±0.03 * | 382±2.14 723±9.45 395±4.54 * 401±5.12 * |
Compare with the blank group of model:
*P＜0.001
Table 5 compositions GCX causes the influence of scorching arthroncus to rat carrageenan
| Group | Dosage (mg/kg) | Toes swelling rate (%) | |||
| 1 | 2 | 3 | 4(h) | ||
| Normal saline group GCX group meticorten group | 300 7.5 | 27.3±5.04 8.7±7.13 * 7.5±4.97 * | 27.6±7.02 12.6±5.81 9.8±8.03 * | 32.4±4.97 15.3±5.97 10.8±5.03 | 34.7±7.41 17.3±6.84 18.5±5.23 |
Compare with the normal saline group:
*P＜0.001
Brief summary: compositions GCX, GC, GX can reduce animal serum uric acid level under the hyperuricemia model, and the Normal animal serum uric acid level is not made significant difference, and can treat and prevent hyperuricemia and gout safely and effectively.GCX can significantly suppress the activity of mouse liver hypoxanthine oxidase (XDH) and xanthine oxidase (XO), and it is relevant with the above-mentioned enzymatic activity of its inhibition to show that GCX reduces hyperuricemia animal serum uric acid level.GCX can reduce K in the inflammation tissue simultaneously
+Content and 5-HT content suppress the rat gouty arthritis that uric acid sodium causes significantly, and protection inflammation tissue can be used for treating gouty arthritis.GCX can significantly reduce the toes swelling that carrageenin causes, show GCX to the early stage telangiectasis of inflammation, permeability increase, pathological changes such as the inflammatory material oozes out, tissue edema have significant inhibitory effect.
Claims (9)
1. the pharmaceutical composition of a gout is characterized in that it is the made medicament of active component by the plant extract of following weight proportion:
Ramulus Cinnamomi Volatile oil 0.1-0.4g, Cacumen Platycladi total flavones 0.5-2g, Rhizoma Chuanxiong total alkaloids 0.4-1.6g.
2. the pharmaceutical composition of a gout is characterized in that by the active component of the extract of following weight proportion made: Ramulus Cinnamomi Volatile oil 0.1-0.4g, Cacumen Platycladi total flavones 0.5-2g.
3. antigout drug compositions according to claim 1 is characterized in that the weight proportion of extract active component is: Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g, Rhizoma Chuanxiong total alkaloids 0.8g.
4. one kind prepares claim 1 anti-gout drugs method for compositions, and its preparation process is as follows:
(1) Ramulus Cinnamomi obtains Ramulus Cinnamomi Volatile oil with supercritical CO 2 extraction, Petroleum ether extraction, vapor extraction or water boiling and extraction;
(2) Cacumen Platycladi is extracted through the 0-95% ethanol water and obtains the Cacumen Platycladi total flavones;
(3) Rhizoma Chuanxiong obtains Rhizoma Chuanxiong total alkaloids through water or sour water one organic solvent, a pure sour water one organic solvent, alkalization one organic solvent, ion exchange resin or vapor extraction;
(4),, promptly get compositions GCX with fully mixing behind the beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil with Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g, Rhizoma Chuanxiong total alkaloids 0.8g.
5. one kind prepares claim 2 anti-gout drugs method for compositions, and its preparation process is as follows:
(1) Ramulus Cinnamomi obtains Ramulus Cinnamomi Volatile oil with supercritical CO 2 extraction, Petroleum ether extraction, vapor extraction or water boiling and extraction;
(2) Cacumen Platycladi is extracted through the 0-95% ethanol water and obtains total flavones in the Cacumen Platycladi;
(3) with fully mixing behind Ramulus Cinnamomi Volatile oil 0.2g, Cacumen Platycladi total flavones 1.0g, the usefulness beta-cyclodextrin inclusion compound Ramulus Cinnamomi Volatile oil, promptly get compositions GC.
6. antigout drug compositions according to claim 4 is characterized in that adding appropriate amount of auxiliary materials in compositions GCX, and the preparation method with conventional can be made into tablet, granule or capsule.
7. antigout drug compositions according to claim 5 is characterized in that adding appropriate amount of auxiliary materials in compositions GC, and the preparation method with conventional can be made into tablet, granule or capsule.
8. the application of the described pharmaceutical composition of claim 1 in the medicine of preparation treatment gout and hyperuricemia.
9. the application of the described pharmaceutical composition of claim 2 in the medicine of preparation treatment gout and hyperuricemia.
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