CN101804098B - Compound cornu cervi degelatinatum preparation as well as preparation method and application thereof - Google Patents
Compound cornu cervi degelatinatum preparation as well as preparation method and application thereof Download PDFInfo
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- CN101804098B CN101804098B CN201010179638.8A CN201010179638A CN101804098B CN 101804098 B CN101804098 B CN 101804098B CN 201010179638 A CN201010179638 A CN 201010179638A CN 101804098 B CN101804098 B CN 101804098B
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Abstract
The invention relates to a compound cornu cervi degelatinatum preparation prepared into tablets or capsules or oral liquid pharmaceutical dosage forms together with a proper pharmaceutical carrier from cornu cervi degelatinatum, herba pyrolae, crinite uraria roots, nidus vespae, mulberry twigs and cassia twigs by a alcohol extraction method; and particularly, the invention relates to a preparation method of the tablets. With another purpose, the invention provides application of the compound cornu cervi degelatinatum preparation in preparing medicines for treating rheumatoid arthritis diseases. The compound cornu cervi degelatinatum preparation can effectively treat rheumatoid arthritis, also gradually reduce the usage amount of hormones in the treatment process of the rheumatoid arthritis and finally replace the hormones, has reasonable prescription and low toxic side effect and is economical and practical.
Description
Technical field
The invention belongs to the field of Chinese medicines, be specifically related to compound recipe Cornu Cervi Degelatinatum preparation and preparation method thereof and application.
Background technology
Rheumatoid arthritis (RA) is a kind of common take pathological changes (subcutaneous nodule, pleuritis, pneumonia etc.) outside chronic, many synovial jointss of symmetry inflammation and joint as the systemic autoimmune disease of main clinical manifestation.Its basic pathological changes is synovitis, then causes osteoclasia and bone etch, can cause late period joint deformity and function to be badly damaged, and brings very large misery thus to patient, and society is caused to white elephant.It is a kind of commonly encountered diseases and frequently-occurring disease, and China's prevalence is 0.3%～0.4%, if not diagnosis and treatment in time, average life will shorten 10～15 years, and 70% patient may be disabled after 2 years, cause the definite cause of disease of rheumatoid arthritis not bright so far, still belong at present a kind of refractory disease.If the drug main hormone medicine of existing treatment rheumatoid arthritis, can not thoroughly treat, large to the toxic and side effects of human body, easily form drug dependence.
Summary of the invention
The object of the invention is to provide a kind of compound recipe Cornu Cervi Degelatinatum preparation, can effectively treat rheumatoid arthritis, in the process for the treatment of rheumatoid arthritis, can gradually reduce hormone dosage simultaneously and finally substitute hormone, reasonable recipe, poisonous side effect of medicine is low, economical and practical; The preparation method of compound recipe Cornu Cervi Degelatinatum preparation is provided simultaneously.Another object of the present invention is to provide the application of a kind of compound recipe Cornu Cervi Degelatinatum preparation in treatment rheumatoid arthritis disease medicament.
Technical scheme of the present invention is as follows:
The weight portion proportioning of raw material of Chinese medicine component of the present invention is:
1～5 part of Cornu Cervi Degelatinatum, 4～8 parts of Herba Pyrolaes, 4～8 parts of Radix Urariae crinitaes, 1～3 part of Nidus Vespae,
1～5 part of Ramulus Mori, 1～5 part of Ramulus Cinnamomi.
Medicine of the present invention raw material of Chinese medicine component optimum weight part proportioning be:
3 parts of Cornu Cervi Degelatinatums, 6 parts of Herba Pyrolaes, 6 parts of Radix Urariae crinitaes, 1 part of Nidus Vespae, 2 parts of Ramulus Moris, 2 parts of Ramulus Cinnamomi.
Described pharmaceutical carrier is micropowder silica gel (SM), carboxymethylstach sodium (CMS), microcrystalline Cellulose (MCC), magnesium stearate, hydroxypropyl methylcellulose.
The preparation method of above-mentioned compound recipe Cornu Cervi Degelatinatum preparation is as follows:
Get Cornu Cervi Degelatinatum, Herba Pyrolae, Herba Urariae crinitae, Nidus Vespae, Ramulus Mori and the Ramulus Cinnamomi of formula ratio;
Ramulus Cinnamomi and Nidus Vespae are extracted respectively to volatile oil and grease, after Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae and Ramulus Mori crude drug are pulverized and 20 times of 60% ethanol extraction of residue of Ramulus Cinnamomi and Nidus Vespae 3 times, temperature is 80 ℃, extracts 6 hours at every turn, and extracting solution concentrate drying obtains extract powder;
Ramulus Cinnamomi Volatile oil and Nidus Vespae grease and micropowder silica gel are ground well, mix homogeneously with extract powder again, add microcrystalline Cellulose and carboxymethylstarch to receive, make in right amount soft material with 2% hydroxypropyl methylcellulose aqueous solution, after dry granulate, add 0.5%～2% magnesium stearate to mix, be pressed into plain sheet with punch die;
Select up-to-standard plain sheet, carry out film coating and make tablet, or make capsule or oral medicine liquid dosage form.
The oral formulations such as the adjuvant of the suitable kind of raw material of Chinese medicine extract cooperation employing of said components or the tablet that substrate is made, capsule, soft capsule, dispersible tablet, granule, effervescent tablet.
Compound recipe Cornu Cervi Degelatinatum preparation of the present invention can adopt the preparation of Chinese medicine preparation conventional method; make conventional at present any preparation; but in order to make the each crude drug of this medicine bring into play better drug effect, preferably adopt and be prepared into the following method tablet, but this can not limit the scope of the invention.
The proportioning of often making 1000 main supplementary materials of tablet is as follows:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel (SM) 100g
Carboxymethylstarch is received (CMS) 30g
Microcrystalline Cellulose (MCC) 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Coating material is made by the raw material of following proportioning, often makes 1000 coating tablets sheets, and the proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
The application of a kind of compound recipe Cornu Cervi Degelatinatum preparation in preparation treatment rheumatoid arthritis disease medicament.
Compound recipe Cornu Cervi Degelatinatum preparation provided by the present invention and preparation method thereof and application, beneficial effect is as follows:
1, medicine of the present invention is the formula of summing up through years of researches according to the Therapeutic Principle of theory of Chinese medical science and modern medicine, wherein, Cornu Cervi Degelatinatum reinforcing the kidney and supporting YANG, the hard marrow of secret essence, strengthening the tendons and bones, invigorating middle warmer has logical, still can blood circulation and channel invigorating; Radix Urariae crinitae, Herba Pyrolae liver and kidney tonifying, expelling wind and removing dampness, dredges sharp joint, anti-inflammation detumescence; Nidus Vespae wind-expelling pain-stopping; Ramulus Mori, the sensible extremity of Ramulus Cinnamomi, circumfluence hundred arteries and veins, get around regulations QI and blood, and heresy is removed eutopic reduction.Whole formula is emphasized strengthening vital QI to eliminate pathogenic factors, and residence is mended and given logically, gentle but imitate goodly, is in the process for the treatment of rheumatoid arthritis, gradually reduces hormone dosage and finally substitutes effective Chinese medicine of hormone.
2, pharmaceutical carrier is preferably micropowder silica gel (SM), carboxymethylstach sodium (CMS), microcrystalline Cellulose (MCC), magnesium stearate, hydroxypropyl methylcellulose.
Described preparation acceptable carrier comprises: the acceptable carrier that is applicable to making oral formulations of absorbent, adhesive, disintegrating agent, diluent and other drug.
Described absorbent is selected from micropowder silica gel (SM), CaSO
4, Al (OH)
3; With appropriate 2% hydroxypropyl methylcellulose aqueous solution granulation, tabletting.Its prescription and evaluation result are in Table 1.Result shows, it is stronger that micropowder silica gel absorbs oil content ability, and hardness is larger during tabletting, and the tablet that makes is bright and clean evenly, disintegrative is good, and other two kinds easier stickings all; Therefore absorbent is preferably micropowder silica gel (SM).
The prescription evaluation result of table 1 absorbent screening
Described adhesive is selected from 20% starch slurry, 10% PVP-K30 (PVP-K30), 2% hydroxypropyl methylcellulose aqueous solution; Carry out respectively in right amount wet granulation, tabletting with above-mentioned adhesive.Its prescription and evaluation result are in Table 2.Result shows, 2% hydroxypropyl methylcellulose aqueous solution adhesion is good, fine powder is less, and the tablet surface that makes is smooth, hardness is larger, and disintegrative is good.And easily bonding of 20% starch slurry granulation, sticking; 10% PVP-K30 (PVP-K30) adhesion is lower, and granulation fine powder is many, sheet pine, and hardness is little.Therefore adhesive is preferably 2% hydroxypropyl methylcellulose aqueous solution.
The prescription evaluation result of table 2 adhesive screening
Described disintegrating agent is selected from that carboxymethylstarch is received (CMS), cross-linking polyethylene pyrrolidone (PVPP), corn starch; With the appropriate appropriate wet granulation granulation of 2% hydroxypropyl methylcellulose aqueous solution, tabletting, its prescription and evaluation result are in Table 3.Result shows, the disintegration that carboxymethylstarch is received (CMS), cross-linking polyethylene pyrrolidone (PVPP) and corn starch all can increase tablet, but the above two performance is more excellent, wherein carboxymethylstarch receive that (CMS) has advantages of that consumption is less, disintegration of tablet fast, uniform particles is tiny after disintegrate.Therefore disintegrating agent is preferably carboxymethylstarch and receives (CMS).
The prescription evaluation result of table 3 disintegrating agent screening
Described diluent is selected from microcrystalline Cellulose (MCC), dextrin, starch; Add respectively appropriate 2% hydroxypropyl methylcellulose aqueous solution wet granulation, tabletting.Its prescription and evaluation result are in Table 4.Result shows, the tablet that microcrystalline Cellulose (MCC) makes has advantages of that smooth surface, hardness and disintegrative are all good, and also has the effect that absorbs preferably volatile oil, and other two kinds of diluent effects are all undesirable.Therefore diluent is preferably microcrystalline Cellulose (MCC).
The prescription evaluation result of table 4 diluent screening
Through orthogonal test, determine the amount of each pharmaceutical carrier again, obtain preferred pharmaceutical carrier prescription.
3, the extracting method of extract powder is preferably alcohol extracting method, and component content and the extraction ratio of extract are high, and drug effect is good.
The extracting method of extract powder is selected from alcohol extracting method and water extraction; Get Ramulus Cinnamomi 100g and pulverize as coarse powder, be placed in round-bottomed flask, add the water of 9～10 times of amounts, soak 1～2h, with reference to vapor distillation device, extract, obtain Ramulus Cinnamomi Volatile oil standby.
Get Nidus Vespae 50g, remove dead pupa, pulverize, be placed in volatile oil extractor and add water 500ml, in 70 ℃ of constant water bath box, heat, reflux, cooling, extract 12 hours, obtain grease and collect standby.
By Cornu Cervi Degelatinatum 150g, Herba Pyrolae 300g, Radix Urariae crinitae 300g, 20 times of 60% ethanol extraction three times for the residue of the fine powder of Ramulus Mori 100g and Ramulus Cinnamomi and Nidus Vespae, temperature is 80 ℃, each extraction 6 hours, collects total extract and concentrates to obtain extractum, dry, obtain extract powder 105.3g, extract powder be taupe brown to yellowish-brown powder, gas perfume (or spice) is different, mildly bitter flavor.Compared with relatively obtaining extract powder with same recipe medical material employing water extraction, evaluation result is in Table 5.
Two kinds of technique contrasts of table 5
| Technique | Total extract powder weight/g | General flavone content (mg/g) | Determination of Hyperoside (mg/g) |
| Alcohol extracting method | 105.3 | 6.01 | 1.12 |
| Water boiling and precipitation with ethanol method | 83.4 | 5.46 | 0.83 |
| Significance | / | P＜0.05 | P＜0.05 |
Result contrast, two kinds of techniques are extracted to such an extent that extract powder has larger difference, and alcohol extracting method obtains extract powder than water extraction gained extractum grain weight 26.3%; Determination of total flavonoids result shows statistical significance, significance (P) < 0.05, and alcohol extracting method is better than water extraction; In two kinds of techniques, Determination of Hyperoside also has statistical significance, significance (P) < 0.05.So analyze from component content and the extraction ratio aspect of extract, alcohol extracting method is better than water extraction.
Experimental results show that the compound recipe Cornu Cervi Degelatinatum sheet of two kinds of explained hereafter, successive administration is after 28 days, suffer from adjuvant-induced arthritis (adjuvant arthritis, AA) rat paw edema degree be improved significantly.From extraction process and the comparison of dosage form aspect, the compound recipe Cornu Cervi Degelatinatum sheet drug effect that alcohol extracting method makes is good.
In the rat blood serum of AA induction, the content compared with normal matched group of IL-18 (IL-18) and tumor necrosis factor-alpha (TNF-α) raises, the content of transforming growth factor-beta (TGF-β) compared with normal matched group declines, between each group, more all there is a statistical significance, significance (P) < 0.05, in Table 6.After successive administration 28 days, in alcohol extracting method compound recipe Cornu Cervi Degelatinatum sheet test group and water extraction compound recipe Cornu Cervi Degelatinatum sheet test group, the value of IL-18 in serum (IL-18), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) and the contrast of AA matched group all have statistical significance, significance (P) < 0.05.Successive administration is after 28 days in alcohol extracting method compound recipe Cornu Cervi Degelatinatum sheet test group and water extraction compound recipe Cornu Cervi Degelatinatum sheet test group, value and the Normal group of IL-18 in serum (IL-18), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) more all have statistical significance, significance (P) < 0.05.
The impact of two kinds of compound recipe Cornu Cervi Degelatinatum sheets of table 6 on IL-18, TNF-α and TGF-β in serum
Note: with the comparison of AA matched group,
*p < 0.05,
*p < 0.01; With Normal group comparison,
△p < 0.05,
△ △p < 0.01; With alcohol deer group to relatively, P < 0.05
As shown in Table 6, alcohol extracting method compound recipe Cornu Cervi Degelatinatum sheet test group is compared with water extraction compound recipe Cornu Cervi Degelatinatum sheet test group, the value of IL-18 in serum (IL-18), transforming growth factor-beta (TGF-β) all has statistical significance, significance (P) < 0.05.The drug effect of alcohol extracting method compound recipe Cornu Cervi Degelatinatum sheet test group is obviously better than water extraction compound recipe Cornu Cervi Degelatinatum sheet test group, and therefore the compound recipe Cornu Cervi Degelatinatum sheet of alcohol extracting method gained is better than the compound recipe Cornu Cervi Degelatinatum sheet of water extraction gained.Comprehensive drug is known, and alcohol extracting method is better than water extraction.
4, the proportioning raw materials scheme optimization of coating solution is:
Internal layer coating liquid proportioning raw materials
Opadry OY-C-7000A
95% ethanol;
The proportioning raw materials of outer coating solution
Opadry OY-21063
95% ethanol,
Prepared tablet appearance color is good, and disintegration is short, and moisture resistance is good, unilateral flat appearance, even.
The proportioning raw materials of coating solution is selected from three kinds of schemes in table 7, carries out coating with three batches of plain sheets of quantity-produced, and technological parameter is certain, and its evaluation result is as table 8.From result, the scheme 1 in table 7 is three kinds of preferred plans in scheme, selects more advanced material, and simple to operate, moisture resistance is good, and film coating layer dissolves fast, within 3 minutes, can dissolve, and sheet disintegrate is fast, and unilateral smooth, color and luster is even.So determine that the proportioning raw materials of coating solution in scheme 1 is preferred version.
The design of table 7 coating solution
| Coating solution | Internal layer | Outer |
| 1 | Opadry OY-C-7000A | Opadry OY-21063 |
| 2 | PVP solution adds titanium dioxide | No. IV, acrylic resin |
| 3 | Acrylic resin adds HPMC No. II | No. II, acrylic resin |
The evaluation result of three kinds of scheme compositions of table 8
| Coating solution | Appearance colour | Disintegration (min) | Sucting wet experiment | Unilateral outward appearance |
| 1 | Light green color, evenly | 15 | Moisture resistance is good | Smooth, evenly |
| 2 | Titanium white color, is shown in the palm fibre end | 25 | Moisture resistance is good | Smooth, inhomogeneous |
| 3 | White, is shown in the palm fibre end | 32 | Moisture resistance is good | More smooth, inhomogeneous |
Through work process optimization, determine that optimum technological parameter is: 45 ℃ of sheet bed tempertaures, rotating speed 10～15r/min, coating solution sprays fast 5ml/ (kg.min), and internal layer coating liquid concentration is 8%, and outer coating solution concentration is 6%.
Therefore, in sum, the preferred preparation method of compound recipe Cornu Cervi Degelatinatum sheet of the present invention is as follows:
(1) get Cornu Cervi Degelatinatum, Herba Pyrolae, Herba Urariae crinitae, Nidus Vespae, Ramulus Mori, the Ramulus Cinnamomi of formula ratio;
(2) Ramulus Cinnamomi and Nidus Vespae are extracted respectively to volatile oil, after Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae and Ramulus Mori crude drug are pulverized and 20 times of 60% ethanol extraction of residue of Ramulus Cinnamomi and Nidus Vespae 3 times, temperature is 80 ℃, extracts 6 hours at every turn, and extracting solution concentrate drying obtains extract powder;
(3) plain tablet recipe:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel (SM) 100g
Carboxymethylstarch is received (CMS) 30g
Microcrystalline Cellulose (MCC) 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Make 1000
Make coating after plain sheet, the prescription of coating solution is as follows:
The proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
(4) Ramulus Cinnamomi Volatile oil and Nidus Vespae grease and micropowder silica gel are ground well, mix homogeneously with extract powder (pulverizing 100 mesh sieves) again, add carboxymethylstarch to receive and microcrystalline Cellulose, with 2% hydroxypropyl methylcellulose aqueous solution, make in right amount soft material, cross 20 mesh sieves and granulate, 55 ℃ of dry 3h in baking oven, cross 18 mesh sieve granulate, add 0.5%～2% magnesium stearate to mix, in the shallow concave punch that is 10.0mm with diameter, be pressed into sheet, obtain plain sheet; Select up-to-standard plain sheet, carry out film coating, obtain finished product.
More than form when producing and can increase or reduce according to corresponding proportion, as large-scale production can with kilogram or take ton as unit, small-scale production also can be in grams, and weight can increase or reduce, but raw medicinal herbs weight proportion constant rate between each component.
Medicine of the present invention can be determined usage and dosage according to patient's situation when taking, and every day, each crude drug consumption was as the criterion with state-promulgated pharmacopoeia dosage, was no more than pharmacopeia ormal weight.
5, the present invention is under instruction of Chinese Medicine theory, the preparation that preparation technology's test that process is a large amount of and pharmacology, pharmacodynamics test obtain.Reasonable recipe of the present invention, poisonous side effect of medicine is low, is the medicine of the definite treatment rheumatoid arthritis of a kind of economy, material benefit, curative effect.
6, add up 1325 routine rheumatoid arthritis (RA) patients between certain hospital in February, 2003～2004 year October, take after three courses for the treatment of of compound recipe Cornu Cervi Degelatinatum sheet, cure rate reaches 50.19%, and total effective rate is 98.26%.120 routine patients with severe symptoms took after three courses for the treatment of of compound recipe Cornu Cervi Degelatinatum sheet, and total effective rate reaches 85.41%.This medicine is also effective for the patient with severe symptoms who relies on hormone therapy, can become and gradually reduce finally effective Chinese medicine of alternative hormone of hormone dosage.
Accompanying drawing explanation
Fig. 1 is compound recipe Cornu Cervi Degelatinatum sheet preparation technology flow chart.
The specific embodiment
Embodiment 1
Get Cornu Cervi Degelatinatum 200g, Herba Pyrolae 800g, Radix Urariae crinitae 800g, Nidus Vespae 200g, Ramulus Mori 200g, Ramulus Cinnamomi 200g;
200g Ramulus Cinnamomi is pulverized as coarse powder, be placed in round-bottomed flask, add the water of 9 times of amounts, soak 2h, with reference to vapor distillation device, extract, obtain Ramulus Cinnamomi Volatile oil standby;
200g Nidus Vespae is removed to dead pupa, pulverize, be placed in the water that volatile oil extractor adds 10 times of amounts, in 70 ℃ of constant water bath box, heat, reflux, cooling, extract 12 hours, obtain grease and collect standby;
Ramulus Cinnamomi and Nidus Vespae residue are dropped into alcohol extraction in total medical material;
By 20 times of 60% ethanol extraction three times for Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae, Ramulus Mori fine powder, temperature is 80 ℃, extracts 6 hours at every turn, collects the concentrated extractum that to obtain of total extract, dry, obtains extract powder.
Get extract powder, pulverized 100 mesh sieves standby.
Element tablet recipe:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel (SM) 100g
Carboxymethylstarch is received (CMS) 30g
Microcrystalline Cellulose (MCC) 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Make 1000
Make coating after plain sheet, the prescription of coating solution is as follows:
The proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
Ramulus Cinnamomi Volatile oil and Nidus Vespae grease are ground well by the micropowder silica gel of recipe quantity and recipe quantity, mix homogeneously with the extract powder (pulverizing 100 mesh sieves) of recipe quantity again, add the carboxymethylstarch of recipe quantity to receive and microcrystalline Cellulose, make in right amount soft material with 2% hydroxypropyl methylcellulose aqueous solution, crossing 20 mesh sieves granulates, 55 ℃ of dry 3h in baking oven, cross 18 mesh sieve granulate, add 10.5%～2% magnesium stearate to mix, in the shallow concave punch that is 10.0mm with diameter, be pressed into sheet, obtain plain sheet; Select up-to-standard plain sheet, carry out film coating, 45 ℃ of sheet bed tempertaures during coating, rotating speed 10～15r/min, coating solution sprays fast 5ml/ (kg.min), obtains compound recipe Cornu Cervi Degelatinatum sheet.
Get Cornu Cervi Degelatinatum 500g, Herba Pyrolae 800g, Radix Urariae crinitae 800g, Nidus Vespae 800g, Ramulus Mori 300g, Ramulus Cinnamomi 300g;
300g Ramulus Cinnamomi is pulverized as coarse powder, be placed in round-bottomed flask, add the water of 10 times of amounts, soak 2h, with reference to vapor distillation device, extract, obtain Ramulus Cinnamomi Volatile oil standby;
800g Nidus Vespae is removed to dead pupa, pulverize, be placed in the water 1 that volatile oil extractor adds 10 times of amounts, in 70 ℃ of constant water bath box, heat, reflux, cooling, extract 12 hours, obtain grease and collect standby;
Ramulus Cinnamomi and Nidus Vespae residue are dropped into alcohol extraction in total medical material;
By 20 times of 60% ethanol extraction three times for Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae, Ramulus Mori fine powder, temperature is 80 ℃, extracts 6 hours at every turn, collects the concentrated extractum that to obtain of total extract, dry, obtains extract powder.
Get extract powder, pulverized 100 mesh sieves standby.
Element tablet recipe:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel (SM) 100g
Carboxymethylstarch is received (CMS) 30g
Microcrystalline Cellulose (MCC) 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Make 1000
Make coating after plain sheet, the prescription of coating solution is as follows:
The proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
Ramulus Cinnamomi Volatile oil and Nidus Vespae grease are ground well by the micropowder silica gel of recipe quantity and recipe quantity, mix homogeneously with the extract powder (pulverizing 100 mesh sieves) of recipe quantity again, add the carboxymethylstarch of recipe quantity to receive and microcrystalline Cellulose, make in right amount soft material with 2% hydroxypropyl methylcellulose aqueous solution, crossing 20 mesh sieves granulates, 55 ℃ of dry 3h in baking oven, cross 18 mesh sieve granulate, add 0.5%～2% magnesium stearate to mix, in the shallow concave punch that is 10.0mm with diameter, be pressed into sheet, obtain plain sheet; Select up-to-standard plain sheet, carry out film coating, 45 ℃ of sheet bed tempertaures during coating, rotating speed 10～15r/min, coating solution sprays fast 5ml/ (kg.min), obtains compound recipe Cornu Cervi Degelatinatum sheet.
Embodiment 3
Get Cornu Cervi Degelatinatum 300g, Herba Pyrolae 600g, Radix Urariae crinitae 600g, Nidus Vespae 100g, Ramulus Mori 200g, Ramulus Cinnamomi 200g;
300g Ramulus Cinnamomi is pulverized as coarse powder, be placed in round-bottomed flask, add the water of 10 times of amounts, soak 2h, with reference to vapor distillation device, extract, obtain Ramulus Cinnamomi Volatile oil standby;
600g Nidus Vespae is removed to dead pupa, pulverize, be placed in the water that volatile oil extractor adds 10 times of amounts, in 70 ℃ of constant water bath box, heat, reflux, cooling, extract 12 hours, obtain grease and collect standby;
Ramulus Cinnamomi and Nidus Vespae residue are dropped into alcohol extraction in total medical material;
By 20 times of 60% ethanol extraction three times for Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae, Ramulus Mori fine powder, temperature is 80 ℃, extracts 6 hours at every turn, collects the concentrated extractum that to obtain of total extract, dry, obtains extract powder.
Get extract powder, pulverized 100 mesh sieves standby.
Element tablet recipe:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel (SM) 100g
Carboxymethylstarch is received (CMS) 30g
Microcrystalline Cellulose (MCC) 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Make 1000
Make coating after plain sheet, the prescription of coating solution is as follows:
The proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
Ramulus Cinnamomi Volatile oil and Nidus Vespae grease are ground well by the micropowder silica gel of recipe quantity and recipe quantity, mix homogeneously with the extract powder (pulverizing 100 mesh sieves) of recipe quantity again, add the carboxymethylstarch of recipe quantity to receive and microcrystalline Cellulose, make in right amount soft material with 2% hydroxypropyl methylcellulose aqueous solution, crossing 20 mesh sieves granulates, 55 ℃ of dry 3h in baking oven, cross 18 mesh sieve granulate, add 0.5%～2% magnesium stearate to mix, in the shallow concave punch that is 10.0mm with diameter, be pressed into sheet, obtain plain sheet; Select up-to-standard plain sheet, carry out film coating, 45 ℃ of sheet bed tempertaures during coating, rotating speed 10～15r/min, coating solution sprays fast 5ml/ (kg.min), obtains compound recipe Cornu Cervi Degelatinatum sheet.
Embodiment 4
The application of a kind of compound recipe Cornu Cervi Degelatinatum preparation in preparation treatment rheumatoid arthritis disease medicament:
The impact of preparation tablet of the present invention to cytokine in the rat blood serum of trouble adjuvant-induced arthritis (adjuvant arthritis, AA)
By 10 outbreeding group rats (SD rat) lift hemostasis complete Freund's adjuvant (CFA) 0.1ml (containing bacillus calmette-guerin vaccine 7.5mg/L) induction AA model after left foot.
By outbreeding group rat (SD rat) random packet, be divided into 7 groups: dosage group, compound recipe Cornu Cervi Degelatinatum sheet low dose group, positive controls 1 (celecoxib in AA model group, Normal group, compound recipe Cornu Cervi Degelatinatum sheet high dose group, compound recipe Cornu Cervi Degelatinatum sheet, 3mg/kg), positive controls 2 (Glucosidorum Tripterygll Totorums, 1mg/kg), 10 every group.After modeling, (after gastric infusion the 28th day) ventral aorta blood sampling in the 44th day, adopts 0.5ml for every, adopts the method for ELISA to detect the concentration of each cytokine in serum, in strict accordance with the operation of ELISA test kit description, the results are shown in Table 8.
The impact of table 8 compound recipe Cornu Cervi Degelatinatum sheet on IL-18, TNF-α and TGF-β in serum
Note: with the comparison of AA matched group,
*p < 0.05,
*p < 0.01; With the comparison of blank group,
△p < 0.05,
△ △p < 0.01
Successive administration 28 days, in the high, medium and low dosage group of compound recipe Cornu Cervi Degelatinatum sheet serum, all there were significant differences for the value of IL-18 (IL-18), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) and the contrast of AA matched group, significance (P) < 0.01.
In compound recipe Cornu Cervi Degelatinatum sheet, in low dose group serum, more all there were significant differences for the value of IL-18 (IL-18), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) and blank group, significance (P) < 0.05; No significant difference compared with compound recipe Cornu Cervi Degelatinatum sheet high dose group.Serology detects and shows that compound recipe Cornu Cervi Degelatinatum sheet can effectively suppress the level of Cytokine of Serum, and the inflammation of the rat synovium of joint of suffering from adjuvant-induced arthritis (adjuvant arthritis, AA) is significantly improved.
Embodiment 5
The application of a kind of compound recipe Cornu Cervi Degelatinatum preparation in preparation treatment rheumatoid arthritis disease medicament:
The mensuration of preparation tablet mice median lethal dose(LD 50) of the present invention (LD50)
12 of regular grade kunming mices, weight 20 ± 2g, male and female half and half, adaptability is fed rear fasting 12 hours, is assigned randomly to the oral acute toxicity of three dosage groups investigation compound recipe Cornu Cervi Degelatinatum sheets, every group of male and female half and half.
By the low dosages of 10 times of reference dose 10mg/kg design chmice acute toxicity, carry out trial test, three dosage groups are respectively 100mg/kg, 200mg/kg, 400mg/kg, and gavage is observed the diet of two weeks interior animals, activity, the situations such as Mao Ze and living or death.
After gastric infusion, animal appearance and behavior are acted normally, and three dosage groups are all without any toxic reaction, and none is poisoned to death.Result shows when 40 times of effective reference dose, without any toxic reaction, to think that compound recipe Cornu Cervi Degelatinatum sheet toxicity rank is very low or nontoxic, and oral safety, does not need to improve dosage again and do toxicity test.
Embodiment 6
The application of a kind of compound recipe Cornu Cervi Degelatinatum preparation in preparation treatment rheumatoid arthritis disease medicament:
The clinical efficacy experiment of preparation tablet in treatment rheumatoid arthritis of the present invention
Add up 156 routine Patients With Rheumatoid Arthritis between certain hospital 3～June in 2004, taking after three courses for the treatment of of compound recipe Cornu Cervi Degelatinatum sheet, clinical cure 84 examples, effective 44 examples, effective 23 examples, invalid 5 examples, cure rate is 53.85%, total effective rate is 96.79%.Immunoglobulin lgG after treatment, lgM, lgA obviously declines, and symptom is obviously improved, and all has significant difference compared with before treatment, the results are shown in Table 9.
Before and after table 9 immunoglobulin therapy, change
| lgG | lgA | lgM | |
| Before treatment | 25.970±2.197 * | 6.758±1.127 * | 6.034±1.138 * |
| After treatment | 16.074±1.378 | 3.489±0.684 | 3.079±0.847 |
Note: compare before and after treatment
*p < 0.05
Claims (3)
1. treat a compound recipe Cornu Cervi Degelatinatum preparation for rheumatoid arthritis disease, it is characterized in that it is the medicament of being made by raw material of Chinese medicine component and the pharmaceutical carrier of following weight parts proportioning:
1～5 part of Cornu Cervi Degelatinatum, 4～8 parts of Herba Pyrolaes, 4～8 parts of Radix Urariae crinitaes, 1～3 part of Nidus Vespae,
1～5 part of Ramulus Mori, 1～5 part of Ramulus Cinnamomi;
The preparation method of above-mentioned compound recipe Cornu Cervi Degelatinatum preparation, as follows:
Get Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae, Nidus Vespae, Ramulus Mori and the Ramulus Cinnamomi of formula ratio;
Ramulus Cinnamomi and Nidus Vespae are extracted respectively to volatile oil and grease, after Cornu Cervi Degelatinatum, Herba Pyrolae, Radix Urariae crinitae and Ramulus Mori crude drug are pulverized and 20 times of 60% ethanol extraction of residue of Ramulus Cinnamomi and Nidus Vespae 3 times, temperature is 80 ℃, extracts 6 hours at every turn, and extracting solution concentrate drying obtains extract powder;
Ramulus Cinnamomi Volatile oil and Nidus Vespae grease and micropowder silica gel are ground well, mix homogeneously with extract powder again, add microcrystalline Cellulose and carboxymethylstach sodium, make in right amount soft material with 2% hydroxypropyl methylcellulose aqueous solution, after dry granulate, add 0.5% ~ 2% magnesium stearate to mix, be pressed into plain sheet with punch die;
Select up-to-standard plain sheet, carry out film coating and make tablet;
The proportioning of supplementary material of often making 1000 tablets of tablets is as follows:
Extract powder 200g
Ramulus Cinnamomi Volatile oil 2.0mL
Nidus Vespae grease 8.5mL
Micropowder silica gel 100g
Carboxymethylstach sodium 30g
Microcrystalline Cellulose 70g
Magnesium stearate 4g
2% hydroxypropyl methylcellulose aqueous solution is appropriate
Coating material is made by the raw material of following proportioning, often makes 1000 coating tablets sheets, and the proportioning raw materials of internal layer coating liquid is:
Opadry OY-C-7000A 12g
95% ethanol 150mL
The proportioning raw materials of outer coating solution is:
Opadry OY-21063 7g
95% ethanol 100mL.
2. a kind of compound recipe Cornu Cervi Degelatinatum preparation for the treatment of rheumatoid arthritis disease according to claim 1, is characterized in that the weight portion proportioning of described raw material of Chinese medicine is:
3 parts of Cornu Cervi Degelatinatums, 6 parts of Herba Pyrolaes, 6 parts of Radix Urariae crinitaes, 1 part of Nidus Vespae, 2 parts of Ramulus Moris, 2 parts of Ramulus Cinnamomi.
3. a kind of compound recipe Cornu Cervi Degelatinatum preparation for the treatment of rheumatoid arthritis disease according to claim 1, is characterized in that: described pharmaceutical carrier is micropowder silica gel, carboxymethylstach sodium, microcrystalline Cellulose, magnesium stearate, hydroxypropyl methylcellulose.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1173365A (en) * | 1997-07-30 | 1998-02-18 | 张巨文 | Chinese medicinal preparation for curing rheumatism and rheumatoid disease and its prepn. method |
| EP1604676A2 (en) * | 2004-06-07 | 2005-12-14 | Kao Corporation | Aromatase transcription activators extracts |
| CN1839974A (en) * | 2006-01-26 | 2006-10-04 | 聂影 | Medicine composition for treating rheumatoid disease and method for preparing the same |
| CN1977899A (en) * | 2005-12-03 | 2007-06-13 | 颜正东 | Medicine for treating rheumatoid arthritis |
-
2010
- 2010-05-24 CN CN201010179638.8A patent/CN101804098B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1173365A (en) * | 1997-07-30 | 1998-02-18 | 张巨文 | Chinese medicinal preparation for curing rheumatism and rheumatoid disease and its prepn. method |
| EP1604676A2 (en) * | 2004-06-07 | 2005-12-14 | Kao Corporation | Aromatase transcription activators extracts |
| CN1977899A (en) * | 2005-12-03 | 2007-06-13 | 颜正东 | Medicine for treating rheumatoid arthritis |
| CN1839974A (en) * | 2006-01-26 | 2006-10-04 | 聂影 | Medicine composition for treating rheumatoid disease and method for preparing the same |
Non-Patent Citations (3)
| Title |
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| 南京中医药大学编著.虎尾轮根.《中药大辞典·上册》.上海科学技术出版社,2006,(第2版),第1880页. * |
| 岳桂华,等.桑枝、桂枝.《名医效验药对 内科卷》.人民军医出版社,2008,(第1版),第318页. * |
| 邱英明等，.朱良春治疗顽痹的经验探要.《福建中医药》.1995,第26卷(第6期),第14-15页，第15页左栏最后一段，右栏第1段. * |
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