CN1965879A - Chinese medicinal effective parts for treating nasal inflammation and preparation process thereof - Google Patents
Chinese medicinal effective parts for treating nasal inflammation and preparation process thereof Download PDFInfo
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- CN1965879A CN1965879A CN 200610095232 CN200610095232A CN1965879A CN 1965879 A CN1965879 A CN 1965879A CN 200610095232 CN200610095232 CN 200610095232 CN 200610095232 A CN200610095232 A CN 200610095232A CN 1965879 A CN1965879 A CN 1965879A
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Abstract
The invention relates to a method for preparing traditional medicine effective component and relative composite, which can treat nasal disease, wherein said component comprises more than 50% of alkanna tinctoria naphthaquinones of alkanna tinctoria. And the preparation comprises that: extracting alkanna tinctoria, recycling alcohol, treating solution with resin, acid, alkali, drying, and breaking; mixing findings, checking and packing. The inventive drug can treat kinds of nasal diseases.
Description
Technical field
The invention belongs to the effective ingredient in Chinese field, be specifically related to a kind of effective ingredient in Chinese and preparation technology thereof who treats nasal cavity inflammation, this effective ingredient in Chinese mainly is made up of the total naphthoquinone compound of Radix Arnebiae (Radix Lithospermi) that the Radix Arnebiae (Radix Lithospermi) raw material is extracted.
Background technology
Radix Arnebiae (Radix Lithospermi) (Radix Arnebiae, Radix lithospermi) is the conventional Chinese medicine material of China, sweet in the mouth, salty, cold in nature, GUIXIN, Liver Channel.Have removing heat from blood, invigorate blood circulation, effects such as detoxifcation rash.Compendium of Material Medica day: Radix Arnebiae (Radix Lithospermi) " is controlled macule, pox poison, promoting blood circulation and cooling blood, sharp large intestine." studies show that Radix Arnebiae (Radix Lithospermi) has resisting pathogenic microbes, antiinflammatory and antiallergic, analgesic, antitumor, protects the liver, hemostasis, blood sugar lowering, calmness and influence effects such as immunologic function.Best a kind of of performance in its main component Alkannia five kinds of natural plants red pigment still commonly used in the world, it is listed in food, cosmetics, drug additive scope by food additive code committee of the United Nations.
The kind that the Pharmacopoeia of the People's Republic of China records is the dry root of lithospermum euchromum Royle Arnebia euchroma (Royle) Johnst, Radix Arnebiae (Radix Lithospermi) Lthospermum erythrorhizon Sieb.Et Zucc. or arnebia guttata Bunge Arnebia guttata Bunge., contains multiple naphthoquinone compound---shikonin and derivant thereof.
Modern pharmacological research, Radix Arnebiae (Radix Lithospermi) have significant antifertility, antiinflammatory, antitumor, sterilizing and anti-virus, protect the liver and effects such as immunomodulating.Pharmacological evaluation proves (Wang Wenjie, platinum leaf etc., shikonin antiinflammatory and to the biosynthetic inhibitory action of leukotriene B4, Acta Pharmaceutica Sinica, 1994,19 (3): 161-165), alcohol extract of Radix Arnebiae (Radix Lithospermi) and acetylshikonin are swollen to rat formaldehyde toes, granuloma induced by implantation of cotton pellets has inhibitory action; Shikonin has inhibitory action to rat formaldehyde toes are swollen, and infers that naphthoquinone compound is determined by its reproducibility the active inhibitory action of 5 one lipoxygenase.Bibliographical information (Xin Chen is arranged, Shikonin, a component ofantiinfammatory Chinese herbal medicine, selectively blocks chemokine binding to CCchemokine receptor-1, International Immunopharmacology, 2001,1:229-236), shikonin is an anti-inflammatory drug that selectivity is very strong, and is very potential aspect the treatment autoimmune disease, for example rheumatic arthritis and multiple sclerosis etc.
Other has clinical report, is that the Radix Arnebiae (Radix Lithospermi) soup treatment of allergic rhinitis of main medicine obtains satisfactory effect (Li Guotong, Radix Arnebiae (Radix Lithospermi) soup treatment of allergic rhinitis, the Shanxi traditional Chinese medical science, 2001,17 (4): 30) with Radix Arnebiae (Radix Lithospermi).With nose dropping treatment allergic rhinitis 126 examples behind the high concentration soaking in Chinese liquor Radix Arnebiae (Radix Lithospermi), cure 89 examples (70.63%) in 7 days, 28 examples that take a turn for the better (22.2%) are cured 102 examples (80.9%), 18 examples that take a turn for the better (14.27%) in 14 days, invalid only 6 examples (4.76%), illustrate that the Radix Arnebiae (Radix Lithospermi) alcohol extract has the good effect of controlling good allergic rhinitis (Chen Peibo, the cognition of high concentration soaking in Chinese liquor Radix Arnebiae (Radix Lithospermi) treatment of allergic rhinitis, the Chinese doctor of community, 2004,20 (266): 43).
But at present the Radix Arnebiae (Radix Lithospermi) infusion is used for the treatment of rhinitis, mainly has the following disadvantages: (1) with the soaking in Chinese liquor Radix Arnebiae (Radix Lithospermi) after collunarium nasal mucosa is stimulated greatly, side effect is obvious; (2) become to be hard to tell, content is not high; (3) can't carry out quality control, curative effect can not guarantee; (4) can not carry out large-scale promotion.At the problems referred to above; the inventor herein has carried out secondary development to Radix Arnebiae (Radix Lithospermi); the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) has been carried out deep research; discovery is effective site or its compositions that raw material extracts with the total naphthoquinone of Radix Arnebiae (Radix Lithospermi); be used for the treatment of the evident in efficacy of allergic rhinitis and be higher than the Chinese liquor crude extract, and the nasal mucosa zest is little, quality controllable; determined curative effect is reliable, is fit to scale, suitability for industrialized production and application.
Summary of the invention
The object of the present invention is to provide a kind of effective ingredient in Chinese for the treatment of nasal cavity inflammation, this effective ingredient in Chinese mainly is made up of the extract that contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) that the Radix Arnebiae (Radix Lithospermi) raw material is extracted, wherein the total naphthoquinone class of Radix Arnebiae (Radix Lithospermi) content accounts for more than 50% of extract weight, wherein the content of Shikonin must not be lower than 1%, the content of preferred Shikonin is not low by 2%, in the weight of extract.
Effective ingredient in Chinese of the present invention has remarkable therapeutic effect through animal experiment to nasal cavity inflammation.
The invention provides a kind of effective ingredient in Chinese compositions for the treatment of nasal cavity inflammation, comprise effective site and the pharmaceutic adjuvant of above-mentioned Radix Arnebiae (Radix Lithospermi).
Another purpose of the present invention provides a kind of preparation method that is applicable to the effective ingredient in Chinese of the present invention of suitability for industrialized production.
Specifically describe
A kind of effective ingredient in Chinese for the treatment of the nasal cavity inflammation disease, this active component composition mainly is made up of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) that the Radix Arnebiae (Radix Lithospermi) raw material is extracted, here the said total naphthoquinone of Radix Arnebiae (Radix Lithospermi) that is extracted by the Radix Arnebiae (Radix Lithospermi) raw material is meant extract or the extractum that contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi), wherein, the total naphthoquinone content of Radix Arnebiae (Radix Lithospermi) accounts for more than 50%, by weight percentage of extract.When the content of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) in the extract reached on 90%, this extract just belonged to the total naphthoquinone of pure Radix Arnebiae (Radix Lithospermi).
The above-mentioned said middle drug effect component composite that has, the effective site of said Radix Arnebiae (Radix Lithospermi), mainly be meant the total naphthoquinone of Radix Arnebiae (Radix Lithospermi), the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) mainly is made up of following effective ingredient: and β monohydroxy isovaleryl shikonin (β-Hydroxyisovalerylshikonin), shikonin (Shikonin), 2,3-dimethyl pentene acyl shikonin (Teracrylshikonin), acetylshikonin (Acetylshikonin), β, beta-dimethyl-acryloyl shikonin (β, β-Dimethylacrylshikonin), isobutyryl shikonin (Isobutylshikonin), a-methyl-positive butyryl shikonin (α-Methyl-n-butyl-shikonin), isovaleryl shikonin (Isovalerylshikonin), dehydrogenation A Kaning (Dehydroalkannin. dehydrogenation iso-alkannin), and a spot of deoxyshikonin chemical compounds such as (Deoxyshikonin).
So-called effective ingredient in Chinese preparation, by Chinese medicine registration management way, the preparation of effective ingredient in Chinese be meant effective site account for extract (extractum) 50% on.
The extract that contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) that described Radix Arnebiae (Radix Lithospermi) is extracted, Shikonin content wherein must not be lower than 1%, by weight.
The effective ingredient in Chinese compositions of treatment nasal cavity inflammation of the present invention comprises effective site and the pharmaceutic adjuvant of above-mentioned Radix Arnebiae (Radix Lithospermi).Described effective site (extract or the extractum that contain the total naphthoquinone of Radix Arnebiae (Radix Lithospermi)) is mixed with pharmaceutic adjuvant or carrier, forms preparation; Said its preparation is: external solid preparation, external use semi-solid preparation, liquid preparation for external application, oral solid formulation, oral liquid or injection.Wherein, the external solid preparation is a powder; The external use semi-solid preparation is gel, ointment, plastering agent, patch; Liquid preparation for external application is liniment, lotion, liquid spray; Oral solid formulation is capsule, tablet, granule, powder or controlled release agent; Oral liquid is oral liquid, syrup or mixture; Injection is injectable powder or injection.
Preferred preparation is a liquid preparation, and described liquid preparation comprises gel, spray or nasal drop.
Effective ingredient in Chinese compositions of the present invention, said liquid preparation, wherein Shikonin content is 0.005-10mg/ml, preferred 0.01-3mg/ml.
Said pharmaceutic adjuvant or carrier are by different preparation or dosage form selection corresponding adjuvant well known in the art or carriers, solid preparation can comprise diluent, disintegrating agent, binding agent, lubricant or correctives etc., and liquid preparation comprises solvent, surfactant, gel-type vehicle or antiseptic etc.
The preparation of preparation is finished according to the preparation method of corresponding preparation well known in the art, can adopt that as tablet direct compression and wet grain granulation are made etc.
The said nasal cavity inflammation of the present invention comprises allergic rhinitis and various acute and chronic rhinitis, sinusitis.
The present invention prepares above-mentioned effective ingredient in Chinese method for compositions, comprises following process:
Radix Arnebiae (Radix Lithospermi) is used solvent extraction 1～3 time, each extraction time is 0.5～8 hour, and extracting solution concentrates, and adds alkali and transfers to apparent approximately alkalescence, through resin 95% ethanol elution, reclaim ethanol, collect eluent, the eluent acid treatment is filtered, precipitation after the collection acid treatment, drying is pulverized, and adds pharmaceutic adjuvant and makes preparation.
In the above-mentioned preparation method, the method for extraction can be circumfluence method, percolation or extraction; Solvent is water or 50～95% ethanol.
The scheme of specific implementation is as follows:
Effective ingredient in Chinese of the present invention is that Radix Arnebiae (Radix Lithospermi) adopts water or alcohol (preferred alcohol) or their mixture equal solvent through circumfluence method, extracting method such as percolation or extraction, extract 1～3 time, each extraction time is 0.5～8 hour, the preferred time is 2～6 hours, extracting solvent load is 5～30 times, and concentration of alcohol is 50%～95%, merge extractive liquid,, reclaim solvent (mainly being ethanol), aqueous solution is through acid, alkali treatment, the precipitation after the collection acid treatment, precipitation is washed to neutrality, dry, the precipitation dissolve with ethanol is crossed resin, the acetone eluting is collected eluent, reclaim acetone, drying is pulverized, acquisition contains the extract or the extractum of the total naphthoquinone of 50% above Radix Arnebiae (Radix Lithospermi), adds pharmaceutical carrier again and makes preparation.Its dosage form comprises that the external solid preparation is a powder; The external use semi-solid preparation is gel, ointment, plastering agent, patch; Liquid preparation for external application is liniment, lotion, liquid spray; Oral solid formulation is capsule, tablet, granule, powder or sustained-release preparation; Oral liquid is oral liquid, syrup or mixture; Injection is injectable powder or injection.
The preparation method of above-mentioned Chinese medicine Radix Arnebiae (Radix Lithospermi) effective site, wherein, the method for extraction can be conventional method such as circumfluence method, percolation or the extraction etc. of Chinese medicine extraction; Solvent is water, ethanol (50～100%), and wherein, the ethanol of the preferred 90-95% of solvent needs to increase the recovery ethanol process.
Effective site of the present invention and compositions thereof have mainly comprised β monohydroxy isovaleryl shikonin (β-Hydroxyisovalerylshikonin), shikonin (Shikonin), 2,3-dimethyl pentene acyl shikonin (Teracrylshikonin), acetylshikonin (Acetylshikonin), β, beta-dimethyl-acryloyl shikonin (β, β-Dimethylacrylshikonin), isobutyryl shikonin (Isobutylshikonin), a-methyl-positive butyryl shikonin (α-Methyl-n-butyl-shikonin), isovaleryl shikonin (Isovalerylshikonin), dehydrogenation A Kaning (Dehydroalkannin. dehydrogenation iso-alkannin), and a spot of deoxyshikonin chemical compounds such as (Deoxyshikonin).
The optional with medicament of the dosage form of effective ingredient in Chinese compositions of the present invention goes up acceptable various additives (use amount is according to the different weight percentage of different agent shapes with the extractum amount).
The preparation of effective ingredient in Chinese compositions of the present invention can adopt the conventional corresponding preparation technology of this area promptly to can be made into pharmaceutically various liquid dosage forms such as various solid dosage formss such as corresponding capsule, tablet, granule, injectable powder, powder, controlled release agent or oral liquid, injection, mixture, syrup etc.
Effective ingredient in Chinese of the present invention has the effect of antiinflammatory, antiallergic, antibiotic, clearing away heat and cooling blood, can be used for the treatment of anaphylactic disease and inflammation.Through the pharmacodynamics preliminary identification, be used for the treatment of allergic rhinitis and acute and chronic rhinitis, sinusitis, respond well.The toxicology test result shows that the safety of this effective ingredient in Chinese compositions is good.
Effective ingredient in Chinese of the present invention, be mainly used in treatment nasal cavity inflammation disease, the preferred gel of its dosage form, spray, nasal drop etc., purple plain total naphthoquinone concentration of its liquid preparation is 0.5mg～50.0mg/ml, preferred 2.5mg～25.0mg/ml is converted into left-handed purple plain concentration and is respectively 0.02mg～2.5mg/ml approximately, preferred 0.1mg～1.25mg/ml, every day is with 1～2 time, each 0.2～0.4ml.Purple plain total naphthoquinone content of its solid or semi-solid system system is 0.5～80%, preferred 1.0～40.0%.
Effective ingredient in Chinese compositions of the present invention adopts conventional drug effect and toxicity test method, and its result is as follows:
Pharmacodynamic experiment of the present invention
Experiment material
1. medicine
Ovalbumin (OVA), SIGMA company, lot number: 9007-8-12
Radix Arnebiae extract, the extractum extraction ratio is 0.6%, contains the total naphthoquinone 54.25% of Radix Arnebiae (Radix Lithospermi), contain Shikonin 3.13%, intranasal formulation concentration (in the effective site of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi)) is respectively 15mg/ml, 10mg/ml, 5mg/ml is equivalent to crude drug 4.6g/ml, 3.1g/ml, 1.5g/ml.
The Radix Arnebiae (Radix Lithospermi) ethanol extraction, the extractum extraction ratio is 6%, contains the total naphthoquinone 3.23% of Radix Arnebiae (Radix Lithospermi), contains Shikonin 0.074%, intranasal formulation concentration is respectively 8.91mg/ml, is equivalent to the 4.6g/ml of crude drug.
2. laboratory animal
Cavia porcellus, 250-300g, male, Chongqing Chinese medicine research institute Experimental Animal Center provides, the quality certification number: SCXK (Chongqing) 20020004.
The Wistar rat, 180-220g, male, Chongqing Chinese medicine research institute Experimental Animal Center provides, the quality certification number: SCXK (Chongqing) 20020004.
Mice, 18-22g, male, Chongqing Chinese medicine research institute Experimental Animal Center provides, the quality certification number: SCXK (Chongqing) 20020004.
3. the effect of effective ingredient in Chinese treatment nosal inflammation of the present invention
1) to the therapeutical effect of the experimental rhinitis of Cavia porcellus of egg albumen sensitization
Whether the total naphthoquinone of this experimentation Radix Arnebiae (Radix Lithospermi) has therapeutical effect to Cavia porcellus experimental rat inflammation, 50 of Cavia porcelluss, every animal lumbar injection ovalbumin 20 μ g, and 5mg Al (OH)
3, every other day once, totally 3 times; After the whole body sensitization, every animal nasal cavity pours into 0.5%OVA 0.1ml, totally 5 days morning and afternoon every day; After the local sensitization, animal is divided into senior middle school's low dose group and normal saline matched group at random, every group 10, the formulation concentrations that the perfusion of treatment group nasal cavity every day contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) is respectively 15mg/ml, 10mg/ml, the liquid formulation 0.1ml of 5mg/ml, solvent matched group pour into normal saline 0.1ml every day, Radix Arnebiae (Radix Lithospermi) ethanol extract (content is 3g Radix Arnebiae (Radix Lithospermi) crude drug/100ml95% ethanol) pours into 0.1ml every day, totally 5 days; Rose in the 2nd day after the last administration, the OVA solution of every animal nasal cavity perfusion 1% excites, and every day 1 time, carries out altogether 7 times.
Observation item:
The sniffle sign: in antigen (or normal saline) collunarium 30 minutes, collunarium was observed after 2 hours 30 minutes again.The sniffle standards of grading, rhinocnesmus: 1 minute, dab nose several times; 2 minutes, scratching nose, face was more than. scouring everywhere.Sneeze: 1 minute, 1～3; 2 minutes, 4～10; On .11 was individual in 3 minutes.Thin nasal discharge 1 minute flow to anterior nares; 2 minutes, surpass anterior nares; 3 minutes, watery nasal discharge was had one's face covered with.Keep the score with the addition method during record, total points surpasses person's model success in 5 fens.
Nasal obstruction: Nabe in 1998 etc. find that respiratory frequency and its nasal airways resistance of Cavia porcellus is good negative correlation on the guinea pig model of allergic rhinitis.Therefore, we adopt respiratory frequency to reflect the nasal airways resistance in this research.Before being stimulated for the 6th time respectively at Cavia porcellus and excite back 10min, 30min, 1h to measure its respiratory frequency.
Histological observation
Then animal subject is put to death, keep viscerocranium, insert in 1% formalin solution behind the fixing 7d nitric acid decalcification with 5%, conventional preparation tissue slice is in light microscopic observation down.According to nasal mucosa edema, hyperemia, inflammatory cell infiltration degree and eosinophilic granulocyte's quantity etc. by inflammation degree scoring (standards of grading: 0: feminine gender, do not have above-mentioned positive pathological characters; 1: slight, tissue edema is not obvious, and inflammatory cell and acidophil are few; 2: moderate, tissue edema is obvious, and inflammatory cell and acidophil amount are medium; 3: severe, tissue edema is serious, the expansion of blood vessel height, inflammatory cell and acidophil amount are many.
The result:
Sniffle, sign scoring dynamic change see Table 1.
Each dosage group of preparation of the present invention and ethanol extraction group are compared with negative control group, and all there were significant differences from the 2nd day (P＜0.05).15mg/ml and 10mg/ml group have significant difference (P＜0.05) with the ethanol extraction group, and the 5mg/ml group is compared no significant difference with the ethanol extraction group.
Table 1 is respectively organized sniffle, sign scoring (x ± S)
| Time | Negative control group (n=10) | Ethanol extraction (n=10) | 15mg/ml (n＝10) | 10mg/ml (n＝10) | 5mg/ml (n＝10) |
| 1d | 6.7±1.1 | 6.6±1.8 | 6.5±1.4 | 6.6±1.7 | 6.4±0.9 |
| 2d | 7.1±1.0 | 6.4±1.3 | 4.1±0.4 | 3.7±1.1 | 5.2±1.6 |
| 3d | 6.5±0.7 | 5.7±1.3 | 3.8±0.7 | 3.6±1.1 | 5.0±1.2 |
| 4d | 6.4±0.7 | 5.0±1.6 | 3.7±1.4 | 3.6±1.5 | 4.8±1.4 |
| 5d | 6.6±1.4 | 4.4±1.4 | 3.7±1.1 | 3.8±1.2 | 4.6±1.5 |
After exciting for the 6th time, the treatment group is at 30min, and the decline of 60min respiratory frequency is obviously delayed in model group (P＜0.05 or＜0.01), sees Table 2.
The contrast of each group calling suction frequency of table 2 (x ± S)
| Time | Negative control group (n=10) | Ethanol extraction (n=10) | 15mg/ml (n＝10) | 10mg/ml (n＝10) | 5mg/ml (n＝10) |
| Before exciting | 101.3±24.3 | 105.3±13.2 | 106.7±11.0 | 98.2±15.2 | 105.7±21.0 |
| 10min | 97.3±14.5 | 96.1±17.2 | 95.5±18.7 | 98.3±12.1 | 97.1±11.3 |
| 30min | 69.1±7.8 | 71.5±13.1 | 97.8±11.2 | 93.9±12.8 | 89.1±6.9 |
| 60min | 77.2±9.7 | 75.4±14.3 | 95.4±9.0 | 90.7±7.6 | 90.8±8.7 |
Each dosage group of preparation of the present invention is compared with negative control group and ethanol extraction group, and all there were significant differences (P＜0.05) from 30min.The ethanol extraction group is compared difference with negative control group not remarkable.
To the histological influence of Cavia porcellus nose
Compare with model control group, each dosage group of preparation of the present invention and ethanol extraction group are compared histo pathological change degree score and are obviously reduced (P＜0.05) with negative control group, acidophil obviously reduces (P＜0.05), the curative effect of 15mg/ml and 10mg/ml group is better than ethanol extract group (P＜0.05), 5mg/ml group and ethanol extraction group difference are not had a significance, see Table 3.
The total naphthoquinone of table 3 Radix Arnebiae (Radix Lithospermi) is to the influence of Cavia porcellus nasal mucosa histo pathological change (x ± S)
| Grouping | The pathological change degree | Acidophil (5 high power lens visual field averages) |
| Matched group | 2.8±0.42 | 7.8±0.41 |
| Ethanol extraction | 1.6±0.43 | 4.1±0.71 |
| 15mg/ml | 0.7±0.48 * | 0.75±0.42 *a |
| 10mg/ml | 1.2±0.63 * | 2.8±0.52 *a |
| 5mg/ml | 1.5±0.85 * | 4.3±0.71 * |
Annotate: compare * P＜0.05 with matched group
Compare with ethanol extraction,
aP＜0.05
The method of this experiment employing ovalbumin whole body sensitization and the local sensitization of per nasal prepares the model of allergic rhinitis, model stability, and good reproducibility, expense is lower, and the time is shorter, is the classical model of estimating treatment of allergic rhinitis.From result of experiment, the total naphthoquinone extractum of Radix Arnebiae (Radix Lithospermi) ethanol extraction and Radix Arnebiae (Radix Lithospermi) can both show the effect of treatment of allergic rhinitis after administration, but the curative effect of the total naphthoquinone extractum of Radix Arnebiae (Radix Lithospermi) (effective site) is better than the Radix Arnebiae (Radix Lithospermi) ethanol extraction.
2) therapeutical effect of the total naphthoquinone nose of Radix Arnebiae (Radix Lithospermi) preparation xylol induced mice auricle edema
The therapeutical effect of the total naphthoquinone of this experimentation Radix Arnebiae (Radix Lithospermi) nose system system xylol induced mice auricle edema
With body weight 25 ~ 30g male mice, be divided into 15mg/ml at random, 10mg/ml, 5mg/ml treatment group, and liquid normal saline negative control group are applied to two sides, ear front and back, a mice left side with dimethylbenzene under slight anesthesia.Repaste is subjected to the reagent thing after half an hour.Every 4 hours, white mice is taken off neck put to death, lay round ear at same position respectively with 9mm diameter card punch, weigh.Every Mus heavily is the swelling degree in auricle weight divided by the auris dextra sheet.The swelling degree of matched group and administration group is carried out statistical procedures.The result is as follows:
The contrast of swelling degree between each group of table 4 (x ± S)
| Grouping | The swelling degree |
| Matched group | 1.54±0.3 |
| Ethanol extraction | 1.36±0.4 * |
| 15mg/ml | 1.11±0.2 *a |
| 10mg/ml | 1.25±0.3 *a |
| 5mg/ml | 1.37±0.3 * |
Annotate: compare * P＜0.05 with matched group
Compare with ethanol extraction,
aP＜0.05
Each agent group of this preparation and ethanol extraction group are compared the swelling degree and are obviously reduced (P＜0.05) with matched group, as seen the mice ear due to this preparation xylol has obvious inhibitory action, the curative effect of 15mg/ml and 10mg/ml group is better than ethanol extraction group (P＜0.05), 5mg/ml group and ethanol extraction group difference are not had a significance, see Table 4.
The total naphthoquinone of table 5 Radix Arnebiae (Radix Lithospermi) is to the influence of mouse peritoneal capillary permeability (x ± S)
| n | Dosage (ml) | Abdominal cavity blood capillary penetrating fluid OD value (570nm) | |
| Matched group | 10 | 0.5 | 0.81±0.11 |
| Ethanol extraction | 10 | 0.5 | 0.77±0.09 |
| 5mg/ml | 10 | 0.5 | 0.77±0.07 |
| 10mg/ml | 10 | 0.5 | 0.41±0.03 * |
| 15mg/ml | 10 | 0.5 | 0.39±0.04 * |
Annotate: compare with matched group,
*P＜0.05
3) mouse peritoneal capillary permeability test: get 50 of kunming mices, the male and female dual-purpose is divided into 5 groups at random, 10 every group.Be divided into normal saline negative control group, ethanol extract group, 15mg/ml, 10mg/ml, 5mg/ml group, every mice administration 0.5ml.1h after the mice administration, tail vein injection 2% AZO-blue normal saline solution 0.1ml/kg body weight, lumbar injection 0.8% acetic acid normal saline solution 0.20ml/ is only immediately, take off cervical vertebra behind the 20min and put to death mice, divide several to wash the abdominal cavity with the 5ml normal saline, 3000 rev/mins, centrifugal 15 minutes; Getting supernatant uses microplate reader in its optical density of 570nm colorimetric determination (OD) value.The result shows: compare with the blank group, total naphthoquinone 15mg/ml of Radix Arnebiae (Radix Lithospermi) and 10mg/ml dosage group abdominal cavity blood capillary penetrating fluid OD value significantly reduce (P＜0.05), see Table 5.
4) the local mucosa medicine irritant experiment of giving of nasal cavity
15 Cavia porcelluss are divided into 3 groups at random, 5 every group, are divided into preparation 15mg/ml group of the present invention, ethanol extraction group and normal saline matched group.To be tried thing in per 15 minutes and be splashed into the animal nasal cavity, be carried out altogether 4 hours, be carried out continuously 3 days.Put to death animal after 24 hours then after last drips medicine, take out the local mucous membrane tissue, histopathologic examination is carried out in section.Found that ethanol extraction group mucosal tissue has obvious congestion and edema, a large amount of inflammatory cell infiltrations, nasal mucosa epithelial cell structure obviously changes, and microvillus reduces or disappears, and irritation is obvious.Preparation 15mg/ml of the present invention group and normal saline group be rarely seen a small amount of inflammatory cell infiltration, and slight congested, no significant difference this shows between the two, and the nasal membrane zest of preparation of the present invention is minimum.
5) oral administration acute toxicity testing
Choose 60 of branch Kunming mouses, male and female half and half, be divided into 6 groups at random, fasting is 24 hours before the experiment, according to the preliminary experiment result, irritate the total naphthoquinone of stomach various dose Radix Arnebiae (Radix Lithospermi) respectively, volume is 40ml/Kg, observe that mice outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death in 7 days.The results are shown in Table 6.
The total naphthoquinone gastric infusion of table 6 Radix Arnebiae (Radix Lithospermi) LD
50Measure
| Group | Dosage (mg/kg) | Number of animals | The dead animal number | Mortality rate | LD 50And confidence limit |
| 1 | 1000 | 10 | 8 | 80 | LD 50=515.585 mg/kg 95% are credible to be limited to 388.01～685.07 |
| 2 | 600 | 10 | 6 | 60 | |
| 3 | 400 | 10 | 4 | 40 | |
| 4 | 300 | 10 | 2 | 20 | |
| 5 | 200 | 10 | 1 | 10 | |
| 6 | 100 | 10 | 0 | 0 |
Quiet, few moving, the perpendicular hair of animal performance, lethargy, dyspnea after administration, administration is urinated after 20 minutes and is that purple, feces are black, and animal has death after 6 hours, and the death time concentrates on 8-30 hour.Dead animal is dissected the perusal heart, liver, spleen, lung, all no abnormal variation of kidney.Statistics animal dead number calculates LD with the Bliss method
50And confidence limit, mouse stomach administration LD
50Be 515.585, the 95% credible 388.01～685.07mg/kg that are limited to.
In sum, the total naphthoquinone extractum of Radix Arnebiae (Radix Lithospermi) of employing the present invention preparation is the content height not only, and preparation technology is simple and practical, and prepared medicine antiinflammatory antiallergic is evident in efficacy, toxicity is little, is suitable for the medical product exploitation.
The specific embodiment
Below in conjunction with specific embodiment, the invention will be further described.
Be limited to the present invention's prescription and be the product of bitter cold, so preparation should be selected the dosage form of energy taste masking or flavoring, as gel, spray, hard capsule, tablet, injection etc.
Embodiment 1: the preparation of this product extract
Prescription Radix Arnebiae (Radix Lithospermi) 20kg
Method for making is got Radix Arnebiae (Radix Lithospermi) and is ground into coarse powder, and the percolation post of packing into adds 5 times of amount soak with ethanol of 85% 8 hours, add 10 times of 85% ethanol percolation again, percolate reclaims ethanol, and aqueous solution adds aqueous alkali and transfers to apparent approximately alkalescence, aqueous alkali limit edged stirs, and is complete until hydrolysis, filters, filtrate transfers to acid and shows acid approximately, fully stirs last standing over night, filter, collecting precipitation, precipitation is washed to neutrality, drying is pulverized and is promptly got extract 123.5g dry powder.
Measure the content of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) in the extract
The content assaying method of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) is with reference to " 2005 editions total naphthoquinone assay methods of a Radix Arnebiae (Radix Lithospermi) of Chinese pharmacopoeia change its vibration extraction into supersound extraction.Concrete operations are as follows, take by weighing the extract 0.5g of the embodiment of the invention 1, put in the 100ml measuring bottle, add ethanol to scale, and ultrasonic 30 minutes, it is fully dissolved, filter.Precision is measured subsequent filtrate 5ml, puts in the 25ml measuring bottle, adds ethanol to scale, shakes all.According to the ultraviolet-visible light spectrophotography, measure absorbance at 516nm wavelength place, be 242 to calculate by the absorptance of Shikonin, the content that promptly gets the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) is 54.25%.
The Shikonin Determination on content
The Shikonin assay method is measured with reference to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With acetonitrile-water-formic acid (500: 500: 0.8) is mobile phase; The detection wavelength is 275nm.
It is an amount of that the preparation precision of reference substance solution takes by weighing the Shikonin reference substance, adds ethanol and make the solution that every 1ml contains 0.10mg, promptly.
Need testing solution must prepare gets the about 50mg of this product powder, and accurate the title decides, and puts in the tool plug conical flask, the accurate ethanol 10ml that adds claims to decide weight, supersound process 30 minutes, put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with ethanol, filter, it is an amount of to get filtrate, and with the microporous filter membrane filtration of 0.45um, promptly getting Shikonin content is 3.13%.
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects liquid chromatograph, measures, promptly.
Embodiment 2
With the Radix Arnebiae extract dry product of embodiment 1 gained, use 95% dissolve with ethanol, last macroporous resin is used the acetone eluting, reclaims acetone, and drying, powder essence obtain powder extracts (Radix Arnebiae (Radix Lithospermi) effective site).Measure by the assay method of implementing 1, the total naphthoquinone (pigment) of its Radix Arnebiae (Radix Lithospermi) is more than 75%.
Embodiment 3: the preparation of gel
Prescription
Radix Arnebiae extract dry powder 0.75g glycerol 100.0g carbomer-940 10.0g
Triethanolamine 10.0g polysorbate-80 10.0g 95% ethanol is an amount of
An amount of purified water of ethylparaben 0.5g Mentholum adds to 1000.0g
Get glycerol and put in the mortar, add carbomer-940, fully grind and make moisteningly, add the about 600ml of purified water again, grinding, make its abundant swelling after, add polysorbate-80 and be dissolved in an amount of alcoholic acid ethylparaben and Mentholum, grind well; To be dissolved in an amount of ethanol Radix Arnebiae extract dry powder again and slowly add, the limit edged grinds, and after being uniformly dispersed, adds triethanolamine, and the limit edged stirs, and makes into gel, adds purified water to full dose, stir evenly, and packing, promptly.
Embodiment 4: the preparation of solution type spray
Prescription
Radix Arnebiae extract dry powder 0.75g ethylparaben 0.5g
The a small amount of Mentholum of sodium pyrosulfite 1.0g 95% ethanol is an amount of
Propylene glycol 100mL purified water adds to 1000mL
Method for making gets that Radix Arnebiae extract dry powder and Mentholum are dissolved in the small amount of ethanol in the prescription, it is slowly added to be dissolved in the propylene glycol ethylparaben solution again, and the limit edged stirs, fully dissolving, add purified water to full dose, stir fully dissolving, filter, packing makes 100 bottles, every bottle of 10mL altogether.
Embodiment 5: the preparation of emulsion-type spray
Prescription
Radix Arnebiae extract dry powder 0.75g hydrogenated vegetable oil 120g ethylparaben 0.5g
An amount of purified water 1000mL of gelatin 80 1.5g surfactants
Method for making gets Radix Arnebiae extract dry powder and ethylparaben adds in the hydrogenated vegetable oil, and the limit is heated with stirring to 60 ℃, as oil phase; Gelatin and surfactant join in the water of 800mL, and 60 ℃ of high-speed stirred mixings are as water; Oil phase is slowly added water, 20000rmin
-1High-speed stirred makes colostrum.Add water to full dose, high-speed stirred, packing makes 100 bottles, every bottle of 10mL altogether.
Embodiment 6: the preparation of suspension type spray
Prescription
Radix Arnebiae extract dry powder 0.75g sodium carboxymethyl cellulose 1.0g glycerol 50g
Oxybenzene formicester 2.0g purified water adds to 1000mL
Method for making is dissolved in the oxybenzene formicester in the purified water, makes rare rubber cement with sodium carboxymethyl cellulose, adds the glycerol mixing, and add Radix Arnebiae extract dry powder again and grind well, packing, making altogether is 100 bottles, every bottle of 10mL.
Embodiment 7: the preparation of hard capsule
Prescription
Radix Arnebiae extract dry powder 4.0g lactose 150g
Sucrose 50g micropowder silica gel 4.0 magnesium stearate 2.0g
Radix Arnebiae extract dry powder during method for making will be write out a prescription adds lactose, with alcohol granulation or dry granulation, is ground into fine powder, and with sucrose, mix homogeneously adds micropowder silica gel and magnesium stearate again, mix homogeneously, 1000 of encapsulated systems, every 0.21g.
Embodiment 8: the preparation of tablet
Prescription
Radix Arnebiae extract dry powder 4.5g starch 240g
Micropowder silica gel 5g magnesium stearate 2.5g
Radix Arnebiae extract dry powder during method for making will be write out a prescription adds starch, with alcohol granulation or dry granulation, is ground into fine powder, and mix homogeneously adds micropowder silica gel, and mix homogeneously adds magnesium stearate again, and tabletting makes 1000, every 0.25g altogether.Reference embodiment: the preparation of alcohol extraction crude product
Prescription
Radix Arnebiae (Radix Lithospermi) 1.0kg
Method for making is ground into coarse powder with Radix Arnebiae (Radix Lithospermi), adds 8 times of amount 95% ethanol mercerations and extracts 3 times, and lixiviate is 10 hours at every turn, merges cooling bath, reclaims ethanol, and aqueous solution concentrates, and is dry below 60 ℃, gets crude product.
The content of measuring the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) by the assay method of implementing 1 with implement 1, implement result's contrast of 2, it the results are shown in Table 7.
Total naphthoquinone of table 7 extract Radix Arnebiae (Radix Lithospermi) and left-handed purple plain content
| Product | The extractum extraction ratio | The content of the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) | Left-handed purple plain content |
| Embodiment 1 | 0.6％ | 54.25％ | 3.13％ |
| Embodiment 2 | 0.4％ | 75.01％ | 4.32％ |
| Reference embodiment | 6％ | 3.23％ | 0.074％ |
From table 7 data show, effective site of the present invention, total naphthoquinone of its active ingredient Radix Arnebiae (Radix Lithospermi) and left-handed purple plain content are apparently higher than the disclosed extract of prior art (Chinese liquor infusion), therefore, make compositions with this effective site, its therapeutic effect is better, medication is more convenient, and compliance improves.
Claims (11)
1, a kind of effective ingredient in Chinese for the treatment of the nasal cavity inflammation disease, it is characterized in that: this effective site mainly is made up of the extract that contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi) that the Radix Arnebiae (Radix Lithospermi) raw material is extracted.
2, effective ingredient in Chinese as claimed in claim 1 is characterized in that: the total naphthoquinone content of Radix Arnebiae (Radix Lithospermi) accounts for more than 50%, by weight percentage of extract.
3, effective ingredient in Chinese as claimed in claim 1 or 2 is characterized in that: the described extract that contains the total naphthoquinone of Radix Arnebiae (Radix Lithospermi), Shikonin content wherein must not be lower than 1%.
4, a kind of effective ingredient in Chinese compositions for the treatment of the nasal cavity inflammation disease comprises claim 1 or 2 described effective ingredient in Chinese and pharmaceutic adjuvants.
5, effective ingredient in Chinese compositions as claimed in claim 4, said its preparation is: external solid preparation, external use semi-solid preparation, liquid preparation for external application, oral solid formulation, oral liquid or injection.
6, effective ingredient in Chinese compositions as claimed in claim 5, said preparation is a liquid preparation.
7, effective ingredient in Chinese compositions as claimed in claim 6, said liquid preparation is characterized in that: Shikonin content is 0.01-3mg/ml.
8, effective ingredient in Chinese compositions as claimed in claim 6 is characterized in that, liquid preparation is gel, spray or nasal drop.
9, a kind of method for preparing the described effective ingredient in Chinese of claim 1 comprises following process:
Radix Arnebiae (Radix Lithospermi) is used solvent extraction 1～3 time, each extraction time is 0.5～8 hour, and extracting solution concentrates, and adds alkali and transfers to apparent approximately alkalescence, through resin 95% ethanol elution, reclaim ethanol, collect eluent, the eluent acid treatment is filtered, precipitation after the collection acid treatment, drying is pulverized, and adds pharmaceutic adjuvant and makes preparation.
10, effective ingredient in Chinese preparation of compositions method as claimed in claim 6, wherein, the method for extraction can be circumfluence method, percolation or extraction; Solvent is water or 50～95% ethanol.
11, effective ingredient in Chinese compositions as claimed in claim 1, wherein said nasal cavity inflammation comprise allergic rhinitis and various acute and chronic rhinitis, sinusitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610095232 CN1965879A (en) | 2006-11-23 | 2006-11-23 | Chinese medicinal effective parts for treating nasal inflammation and preparation process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610095232 CN1965879A (en) | 2006-11-23 | 2006-11-23 | Chinese medicinal effective parts for treating nasal inflammation and preparation process thereof |
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| CN1965879A true CN1965879A (en) | 2007-05-23 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104398579A (en) * | 2014-11-03 | 2015-03-11 | 郝杰 | Nasal drops and preparation method thereof |
| CN106389397A (en) * | 2016-09-19 | 2017-02-15 | 重庆三峡医药高等专科学校 | Application of alkannin in preparation of medicine for treating upper and lower respiratory tract allergic disease |
| CN106665617A (en) * | 2016-11-17 | 2017-05-17 | 内蒙古农业大学 | Botanical mice composite sterilant preparation method |
-
2006
- 2006-11-23 CN CN 200610095232 patent/CN1965879A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104398579A (en) * | 2014-11-03 | 2015-03-11 | 郝杰 | Nasal drops and preparation method thereof |
| CN106389397A (en) * | 2016-09-19 | 2017-02-15 | 重庆三峡医药高等专科学校 | Application of alkannin in preparation of medicine for treating upper and lower respiratory tract allergic disease |
| CN106389397B (en) * | 2016-09-19 | 2018-12-21 | 重庆三峡医药高等专科学校 | Alkannin is preparing the application in the drug for treating upper lower respiratory tract allergic disease |
| CN106665617A (en) * | 2016-11-17 | 2017-05-17 | 内蒙古农业大学 | Botanical mice composite sterilant preparation method |
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Open date: 20070523 |