CN104997843A - Application of selfheal extract for making blood uric acid decreasing medicine or food - Google Patents
Application of selfheal extract for making blood uric acid decreasing medicine or food Download PDFInfo
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- CN104997843A CN104997843A CN201510478718.6A CN201510478718A CN104997843A CN 104997843 A CN104997843 A CN 104997843A CN 201510478718 A CN201510478718 A CN 201510478718A CN 104997843 A CN104997843 A CN 104997843A
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Abstract
The invention relates to new application of a traditional Chinese medicinal material selfheal extract. The selfheal extract can restrain synthesis of blood uric acid in the body by restraining xanthine oxidase activity, the pharmacological activity of decreasing blood uric acid is brought into play, and therefore the selfheal extract can be applied to making medicine or food for preventing and treating hyperuricemia or gout or other diseases. Tests prove that the selfheal extract has the pharmacological activity of remarkably restraining the activity of xanthine oxidase in vitro and decreasing synthesis of blood uric acid in the body. According to the selfheal extract, water or hydrous ethanol can be used as a solvent, heating is carried out for extraction, extraction is carried out one to three times, decoction dregs are removed, vacuum concentration is carried out to remove the solvent, auxiliary materials are added, and then selfheal extract is made into food or a traditional Chinese medicine preparation in dosage forms such as capsules, tablets, oral liquid or solid drink and the like.
Description
Technical field
This patent relates to the application of a kind of Spica Prunellae extract in the medicine or food of preparation reduction blood uric acid, is particularly applied to prevention or the therapeutic use of clinical hyperuricemia or people with high uric acid.
Background technology
Spica Prunellae (Prunella vulgaris L), also known as doing in ferrum color grass, large headdress flower, excellent stigma flower, Intestinum caprae seu ovis dish, Spica Prunellae hammer grass, June, caput post etc.Spica Prunellae nutrition comparatively horn of plenty, containing compositions such as protein, fat, carbohydrate, carotene, vitamin B2, nicotinic acid and vitamin Cs in young stem and leaf.In addition, also containing Saponin, rutin, Spica Prunellae glycoside, hyperin and volatilization wet goods.
Spica Prunellae is cold in nature, sweet in the mouth, pungent, micro-hardship, there is the effect of letting out clearly liver-fire, mass dissipating and swelling eliminating, heat-clearing and toxic substances removing, expelling phlegm for arresting cough, cooling blood for hemostasis, be applicable to lymphoid tuberculosis, goiter, acute mastitis, the vertigo, facial hemiparalysis, bones and muscles pain, pulmonary tuberculosis, metrorrhagia, leukorrhagia, Fiedeler's disease type hepatitis and bacillary dysentery etc.Modern pharmacological research shows, Spica Prunellae has the effect reduced blood pressure, and energy blood vessel dilating, contained by it, rutin has antiinflammatory action, and can reduce vascular permeability, reduces fragility, reduces liver fat; Spica Prunellae also has the effect of resisting cancerous cell.Compendium of Material Medica and Li lay Buddhist " Yi Jianfang ", Spica Prunellae controls ophthalmalgia, and with granulated sugar water logging one ight, get it and can separate interior-heat, slow liver-fire also.Lou Quan is apt to cloud, Spica Prunellae control order pearl pain to night then notably, the magical effect, or with bitter cold snack made with traditional Chinese medicines instead notably, the also magical effect.
Hyperuricemia is also known as gout (gout), it is the disease caused by one group of purine metabolic disturbance, gouty acute arthritis recurrent exerbation, tophaceous deposition that its clinical characters is hyperuricemia (hyperuricemia) and causes therefrom, tophaceous chronic arthritis and joint deformity, often involve kidney and cause chronic interstitial nephritis and uric acid kidney stones to be formed.Hyperuricemia is also known as gout (gout), it is the disease caused by one group of purine metabolic disturbance, gouty acute arthritis recurrent exerbation, tophaceous deposition that its clinical characters is hyperuricemia (hyperuricemia) and causes therefrom, tophaceous chronic arthritis and joint deformity, often involve kidney and cause chronic interstitial nephritis and uric acid kidney stones to be formed.
Xanthine oxidase is oxidase important in human body, the main metabolism participating in nucleic acid, can generate xanthine by catalysis hypoxanthine, then generate uric acid and free radical further.It is by 1330 Amino acid profiles, and its aminoacid sequence has the homology of 90% between Mus and people, is made up of the construction unit of two full symmetrics.Each construction unit is 145, and its catalytic center comprises a molybdenum pterin center, two ferrum-sulfur centers and a flavin adenine dinucleotide (FAD), and wherein molybdenum pterin center is the critical sites that xanthine oxidase catalysis xanthine generates uric acid.Effective suppression XOD activity can reduce the conversion of xanthine to uric acid, thus can treat hyperuricemia.
Should give Drug therapy as early as possible after gout acute onset, non-steroid antiinflammatory drug, colchicine, glucocorticoid, be the first-line treatment medicine of gouty arthritis acute attack.Degree and the affected joints position of arthralgia are depended in the selection of medicine.For the light moderate pain patient in joint, one or several Minor articulus, or 1-2 large joint involvement, optional non-steroid antiinflammatory drug, colchicine or glucocorticoid.To joint severe pain patient, multi-joint is got involved or 1 ~ 2 large joint involvement, can conbined usage non-steroid antiinflammatory drug and colchicine, or glucocorticoid and Effects of Colchicine In Treating.For patient-selectable's interleukin 1 receptor antagonist that initial therapy is invalid.Suppressing the medicine of blood uric acid synthesis to be by suppressing xanthine oxidase, blocking hypoxanthine and transforming to xanthine and uric acid, thus reducing serum Uric Acid Concentration, reduce urate in joint and surrounding tissue deposition thereof, the final outbreak reducing gout.Representing medicine is allopurinol and Febustat.Allopurinol (allopurin01) is competitive xanthine oxidase inhibitor, is just approved for treatment gout, clinically the choice drug of Chang Zuowei uric acid resisting as far back as the sixties in 20th century.
Although developed the medicine of multiple treatment hyperuricemia clinically, these medicines have all had larger side effect, and clinical practice is subject to a definite limitation; From natural plants or Chinese crude drug, find that new medicine has good development prospect.Chinese invention patent CN104162063 reports a kind of compound Chinese medicinal preparation for the treatment of hyperuricemia and preparation method thereof, with natural Chinese medicine Radix Gentianae for primary raw material; Chinese patent CN103372159A reports a kind of SEMEN COICIS extract with uric acid resisting effect and preparation method thereof etc.At present, domestic and foreign literature is not reported that Spica Prunellae extract has and is fallen blood uric acid activity.
This research is by finding that Spica Prunellae extract has significant enzyme inhibition activity in the outer xanthine oxidase inhibitor process of screen body, and find the activity of uric acid resisting in its Mice Body further, prove that it can be used in the treatment of clinical hyperuricemia or the dietetic therapy of people with high uric acid.
Summary of the invention
The object of this invention is to provide a kind of application newly of Chinese crude drug Spica Prunellae extract.
The technical solution used in the present invention is as follows:
Spica Prunellae extract preparation reduce blood uric acid medicine, in an application, it is characterized in that: described Spica Prunellae extract is adopted and prepared with the following method: take Spica Prunellae as raw material, by solvent extraction and concentrated, obtain described Spica Prunellae extract.Wherein, described food comprises bread and cheese, health food and special medicine purposes formula food.
Described Spica Prunellae extract is applied to the medicine of preparation treatment uric acid people with too high.
Preferably, described Spica Prunellae extract is applied to medicine or the food of preparation treatment or prevention hyperuricemia or gout.
Wherein, when described solvent is water, the ratio of weight and number of water and Spica Prunellae is 5-10:1.
Wherein, when described solvent is aquiferous ethanol, the volumn concentration of aquiferous ethanol is 10%-90%, is preferably 10%-40%; The ratio of weight and number of described aquiferous ethanol and Spica Prunellae is 30-50:1.
Wherein, the time of described extraction is 1-4 hour at every turn; Be preferably 2 hours.
Wherein, the mode of extraction used is reflux, microwave or ultrasound assisted extraction; Extraction time is 1-3 time, preferably extracts 2 times.
Wherein, by adding the adjuvant allowed in pharmaceutics or food, described Spica Prunellae extract is made for corresponding pharmaceutical preparation or food formulation solid beverage.
Preferably, described pharmaceutical preparation is tablet, capsule, oral liquid.
Of the present invention have in Spica Prunellae extract of uric acid resisting effect and preparation method thereof, commercially available Spica Prunellae dry product is used to be raw material, through solvent extraction, concentrate, add various adjuvant and make various peroral dosage form, as clinical uric acid resisting medicine or food, for clinical hyperuricemia or ventilation disease treatment or prevention.
The preparation method of described Spica Prunellae extract is as follows:
With water or aquiferous ethanol for Extraction solvent, heating and refluxing extraction, extracts 1-3 time, and concentrating under reduced pressure condition is gone down and desolventized, and adds adjuvant and makes various peroral dosage form;
Extraction solvent is water or aquiferous ethanol, and wherein, the volumn concentration of ethanol is 10%-90%, is preferably 40%-90%.Solvent and quality of medicinal material are than being 10-50:1;
Extracting mode comprises the general Traditional Chinese medicine extraction method such as reflux, extract, microwave or ultrasound assisted extraction.
The extract using Spica Prunellae to prepare adds the preparation of suitable adjuvant becomes corresponding dosage form.
Spica Prunellae of the present invention does not limit source, comprises all Spica Prunellae kinds.
The present inventor screens in vitro in xanthine oxidase inhibitor process and finds that Spica Prunellae extract has significant xanthine oxidase inhibitory activity, imply that it has the function suppressing blood uric acid synthesis in body, and use mouse in vivo models to prove to reduce in its body the function of blood uric acid further.Therefore, Spica Prunellae extract provided by the present invention possesses and significantly falls blood uric acid purposes, and can make multiple dosage form, for prevention or the treatment of hyperuricemia or gout.
The invention has the advantages that: the active component of medicine or dietary product is single, the extraction process of active component is simple, and find the pharmacologically active that its good reduction uric acid synthesizes, externally prove that it has significant uric acid resisting function with in vivo test, laboratory animal does not have apparent side effect.
Detailed description of the invention
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, all conventionally and condition, or selects according to catalogue.Raw material in following embodiment is commercially available.
Embodiment 1
The preparation of Spica Prunellae extract capsule
Take Spica Prunellae 100 grams, add water 500ml mineral water or deionized water, and soak 2 hours, heating and refluxing extraction 2 hours, temperature is 80-100 DEG C, takes out extracting solution; Add 500ml water to extract 1 time equally again, merge and obtain 950ml extracting solution altogether, be evaporated to slurry; Add microcrystalline Cellulose according to 1:1 ratio, mixing, oven dry, pulverizing, add 1% magnesium stearate mix homogeneously, dress hard capsule.
Embodiment 2
The preparation of Spica Prunellae extract tablet
Take 50 grams of Spica Prunellaes, add 1500ml 90% ethanol water, soak 2 hours, heating and refluxing extraction 2 hours, temperature is 100 DEG C, takes out extracting solution; Add 1500ml 90% ethanol water more equally to extract once, merge extractive liquid, is evaporated to slurry, adds microcrystalline Cellulose according to 1:1 ratio, mixing, oven dry, pulverizing, with disintegrating agent and other adjuvant mix homogeneously, granulates, tabletting.
Embodiment 3
The preparation of Spica Prunellae extract solid beverage
Take 50 grams of Spica Prunellaes, add 2500ml 40% ethanol water, soak 2 hours, ultrasonic or microwave radiation exaraction 2 hours, take out extracting solution; Add 2500ml 40% ethanol water more equally to extract once, merge extractive liquid, is evaporated to slurry, adds microcrystalline Cellulose according to 1:1 ratio, and mixing, oven dry, pulverizing, add other adjuvants, granulates, pack.
Embodiment 4
The preparation of Spica Prunellae extract oral liquid
Take 50 grams of Spica Prunellaes, add 2500ml 10% alcoholic solution, soak 2 hours, heating and refluxing extraction 2 hours, temperature is 90 DEG C, takes out extracting solution; Add 2500ml 10% alcoholic solution more equally to extract once, merge extractive liquid, is evaporated to slurry, adds microcrystalline Cellulose according to 1:1 ratio, and mixing, oven dry, pulverizing, add general disintegrating agent and other adjuvants, mix homogeneously, makes oral liquid.
Embodiment 5
The preparation of Spica Prunellae extract solid beverage
Take 50 grams of Spica Prunellaes, add 1500ml 40% ethanol water, soak 2 hours, ultrasonic or microwave radiation exaraction 2 hours, take out extracting solution; Add 1500ml 40% ethanol water more equally to extract once, merge extractive liquid, is evaporated to slurry, adds microcrystalline Cellulose according to 1:1 ratio, and mixing, oven dry, pulverizing, add other adjuvants, granulates, pack.
Embodiment 6
The preparation of Spica Prunellae extract oral liquid
Take Spica Prunellae 100 grams, add water 1000ml deionized water, and soak 2 hours, heating and refluxing extraction 2 hours, temperature is 80-100 DEG C, takes out extracting solution; Add 1000ml water to extract 1 time equally, merge extractive liquid, is evaporated to slurry, adds microcrystalline Cellulose according to 1:1 ratio again, and mixing, oven dry, pulverizing, add general disintegrating agent and other adjuvants, mix homogeneously, makes oral liquid.
Embodiment 7
Spica Prunellae extract vitro inhibition xanthine oxidase activity
1. preparation of reagents
Preparation: 70mM phosphate buffer (pH 6.5); 0.3mM xanthine solution (2.28mg xanthine is dissolved in 50ml70mM phosphate buffer); Preparation xanthine oxidase solution (0.01U/ml is in 70mM phosphate buffer); 1N HCL solution (the dense HCL of 8.5ml is in 91.5ml water).
Positive control drug: allopurinol
Other medicines: DMSO solution
Given the test agent: prepare by embodiment 1-6.
2. give the preparation of drug solns:
Test sample solution: the sample (containing Spica Prunellae extract 2mg) of embodiment 1-6 is dissolved in 1ml DMSO, is mixed with 2mg/ml solution.Dilute 10 times with PBS buffer again, obtain the solution containing Spica Prunellae extract 200 μ g/ml.
Positive reference substance solution: 1mg allopurinol is dissolved in 1ml DMSO, then after diluting 180 times with PBS buffer, obtain the solution containing allopurinol 40 μm of ol/mL.
3. step operation:
Use 96 hole versions to carry out enzyme reaction, get the 70mM phosphate buffer of 35 μ l successively, 50 μ l test sample solutions or positive reference substance solution and 30 μ l enzymatic solution add a reaction tank, positive control adds other adenine solution; Enzyme reaction compound hatches 15 minutes at 37 DEG C, is adding 60 μ l xanthine substrate solutions, reacts 30 minutes, add 25 μ l 1N HCL cessation reactions at 25 DEG C.The absorbance data of solution in each reaction tank under 295nm is read in Bio-Tek microplate reader.Calculate the suppression ratio of each sample.
According to formulae discovery extract sample to the suppression ratio of XOD.
Suppression ratio (%)=[(E
standard substance-E
sample)]/E
standard substance× 100%
4. measurement result:
Table 1 Spica Prunellae extract is to xanthine oxidase external activity inhibit activities (enzyme linked immunosorbent assay)
| Example weight: 2mg | Suppression ratio (%) |
| Other purine (positive control) | 95 |
| The ulcerative colitis of embodiment 1 | 75 |
| The Spica Prunellae tablet of embodiment 2 | 65 |
| The Spica Prunellae beverage solid beverage of embodiment 3 | 71 |
| The Spica Prunellae oral liquid of embodiment 4 | 78 |
| The Spica Prunellae beverage solid beverage of embodiment 5 | 75 |
| The Spica Prunellae oral liquid of embodiment 6 | 77 |
Result shows, the various extracting method of Spica Prunellae prepares extract and various dosage form all shows stronger xanthine oxidase inhibitory activity, slightly lower than the other purine of clinical chemical medicine.
Embodiment 8
1, laboratory animal ICR, male, about body weight 22g.By Shanghai, western pul-Bi Kai laboratory animal company limited provides, animal productiong credit number: SCXK (Shanghai) 2013-0016.
2, sample is tested
The Spica Prunellae extract capsule of embodiment 1, the Spica Prunellae extract tablet of embodiment 2, the Spica Prunellae extract solid beverage of embodiment 3, the Spica Prunellae extract oral liquid of embodiment 4, the Spica Prunellae extract solid beverage of embodiment 5, the Spica Prunellae extract oral liquid of embodiment 6.Positive control drug: allopurinol
3, instrument and reagent
Automatic clinical chemistry analyzer ZY-260, China of section
4, to the preparation of drug solns:
Test sample solution: the sample preparation of embodiment 1-6 is become the 0.5% sodium cellulosate solution containing Spica Prunellae extract 75mg/ml
Positive reference substance solution: the 0.5% sodium cellulosate solution of allopurinol 12.5mg/ml
5, experimental technique:
Mice is divided into model group, positive drug allopurinol (50mg/kg) group, above six sample sets.Each mouse peritoneal injection hypoxanthine 1000mg/kg (0.2ml/10g), normal group injection water; Model group gavage isometric(al) distilled water, other sample sets give corresponding test sample medicinal liquid and positive reference substance solution, and administration volume is 0.2ml/10g, each group gavage 1 time/d, continuous 5d.
6, serum uric acid
Mice fasting can't help water 16 hours, and after last administration 30min, the aqueous suspension (600mg/kg) of each group lumbar injection HX (full name is: Hypoxanthlne, hypoxanthine), volume injected is 0.2mL/10g.Pluck eyeball after injection HX 45min and get blood 0.5mL, place 30 minutes, rotating speed is 5000rpm, centrifugal 5min, separation of serum, adopts automatic clinical chemistry analyzer and imported reagents thereof to measure serum uric acid concentration.
Table 2 Spica Prunellae extract causes the impact of antihyperuricemic disease mouse model serum UA (uric acid) to ip HX (i.e. Intraperitoneal injection of hypoxanthine)
##p < 0.01vs normal group, * p < 0.01, * * p < 0.01vs model group.
Result shows, the various extracting method of Spica Prunellae prepares extract and various dosage form all shows reduction blood uric acid activity in stronger Mice Body, all has significant difference with model, more weak than positive drug activity.
Claims (10)
1. the application of Spica Prunellae extract in the medicine or food of preparation reduction blood uric acid, is characterized in that: described Spica Prunellae extract is adopted and prepared with the following method: take Spica Prunellae as raw material, by solvent extraction with concentrated, obtains described Spica Prunellae extract.
2. the application of Spica Prunellae extract according to claim 1, is characterized in that, described food comprises bread and cheese, health food and special medicine purposes formula food.
3. the application of Spica Prunellae extract according to claim 1, is characterized in that, it is applied to medicine or the food of preparation treatment or prevention hyperuricemia or gout.
4. the application of Spica Prunellae extract according to claim 1, it is characterized in that, the described solvent of use is water or aquiferous ethanol, and the ratio of weight and number of described solvent and Spica Prunellae is 5-50:1.
5. the application of Spica Prunellae extract according to claim 4, it is characterized in that, when described solvent is water, the ratio of weight and number of water and Spica Prunellae is 5-10:1.
6. the application of Spica Prunellae extract according to claim 4, it is characterized in that, when described solvent is aquiferous ethanol, the volumn concentration of aquiferous ethanol is 10%-90%, is preferably 10%-40%; The ratio of weight and number of described aquiferous ethanol and Spica Prunellae is 30-50:1.
7. the application of Spica Prunellae extract according to claim 1, it is characterized in that, the time of described extraction is 1-4 hour at every turn; Be preferably 2 hours.
8. the application of Spica Prunellae extract according to claim 1, it is characterized in that, the mode of extraction used is reflux, microwave or ultrasound assisted extraction; Extraction time is 1-3 time, preferably extracts 2 times.
9. the application of Spica Prunellae extract according to any one of claim 1-8, is characterized in that, by adding the adjuvant allowed in pharmaceutics or food, described Spica Prunellae extract being made for corresponding pharmaceutical preparation or food formulation solid beverage.
10. the application of Spica Prunellae extract according to claim 9, it is characterized in that, described pharmaceutical preparation is tablet, capsule, oral liquid.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114532468A (en) * | 2022-03-03 | 2022-05-27 | 华中农业大学 | Efficacy-enhanced artemisia selengensis leaf uric acid-reducing beverage |
| CN115364179A (en) * | 2022-08-29 | 2022-11-22 | 吉林省中医药科学院（吉林省中医药科学院第一临床医院） | Traditional Chinese medicine composition for reducing blood uric acid and preparation method and application thereof |
| CN116920001A (en) * | 2022-03-30 | 2023-10-24 | 福建中益制药有限公司 | Traditional Chinese medicine composition for reducing hyperuricemia and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1559519A (en) * | 2004-02-18 | 2005-01-05 | 江苏康缘药业股份有限公司 | Prunella spike extract and its preparation method and use |
-
2015
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1559519A (en) * | 2004-02-18 | 2005-01-05 | 江苏康缘药业股份有限公司 | Prunella spike extract and its preparation method and use |
Non-Patent Citations (1)
| Title |
|---|
| 岳美中著: "《岳美中全集》", 31 March 2012, 中国中药出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114532468A (en) * | 2022-03-03 | 2022-05-27 | 华中农业大学 | Efficacy-enhanced artemisia selengensis leaf uric acid-reducing beverage |
| CN116920001A (en) * | 2022-03-30 | 2023-10-24 | 福建中益制药有限公司 | Traditional Chinese medicine composition for reducing hyperuricemia and preparation method thereof |
| CN115364179A (en) * | 2022-08-29 | 2022-11-22 | 吉林省中医药科学院（吉林省中医药科学院第一临床医院） | Traditional Chinese medicine composition for reducing blood uric acid and preparation method and application thereof |
| CN115364179B (en) * | 2022-08-29 | 2024-02-06 | 吉林省中医药科学院（吉林省中医药科学院第一临床医院） | Traditional Chinese medicine composition for reducing blood uric acid as well as preparation method and application thereof |
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Effective date of registration: 20160718 Address after: 200040 Beijing West Road, Shanghai, No. 1320, No. Applicant after: Shanghai Institute of pharmaceutical industry Address before: 430000 East Lake Hubei Development Zone, high tech Avenue, No. A20, building 666, Applicant before: Co., Ltd of health industry research institute of traditional Chinese medicines group Applicant before: China State Institute of Pharmaceutical Industry |
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Application publication date: 20151028 |