CN112915066B

CN112915066B - Glabrous sarcandra herb formula granules and preparation method thereof

Info

Publication number: CN112915066B
Application number: CN202110374829.8A
Authority: CN
Inventors: 张丽艳; 唐靖雯; 卢礼平; 潘梅; 梁斌; 彭政忠; 潘婷; 杨桃; 王欢
Original assignee: Guizhou Warmen Pharmaceutical Co ltd
Current assignee: Guizhou Warmen Pharmaceutical Co ltd
Priority date: 2021-04-08
Filing date: 2021-04-08
Publication date: 2022-09-09
Anticipated expiration: 2041-04-08
Also published as: CN112915066A

Abstract

The invention relates to glabrous sarcandra herb formula granules and a preparation method thereof. The preparation method of the glabrous sarcandra herb formula particle comprises the following steps: decocting glabrous sarcandra herb for three times, adding water 6-10 times the weight of the medicinal materials for the first time, decocting for 0.5-2 hours, and filtering to obtain filtrate for later use; adding 5-7 times of water for the second time and the third time respectively, decocting for 0.5-2 hours each time, and filtering; mixing the three filtrates, mixing, concentrating under reduced pressure, and spray drying to water content below 9% to obtain powdered dry extract; and (3) uniformly mixing 1 part by weight of dry paste with 0.1-0.2 part by weight of dextrin, and performing dry granulation on a dry granulator to obtain the glabrous sarcandra herb formula granules. The herba Pileae Scriptae is dried whole herb of Sarcandra glabra (Thunb.) Nakai of Chloranthaceae. The traditional Chinese medicine formula particle has the functions of clearing heat and cooling blood, promoting blood circulation and removing speckles, and dispelling wind and dredging collaterals, and can be used for treating blood heat, speckle and eruption, rheumatic arthralgia and traumatic injury.

Description

Glabrous sarcandra herb formula granules and preparation method thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, relates to a traditional Chinese medicine formula particle, and particularly relates to a glabrous sarcandra herb formula particle which has the functions of clearing heat and cooling blood, promoting blood circulation and removing spots, and dispelling wind and dredging collaterals and is used for treating blood heat, macula and eruption, rheumatic arthralgia and traumatic injury. The invention also relates to a preparation method of the glabrous sarcandra herb formula particles and pharmaceutical application of the glabrous sarcandra herb formula particles.

Background

Herba Pileae Scriptae is dry whole plant of sarcandra glabra (Thunb.) nakai of Chloranthaceae. Collected in summer and autumn, removed of impurities and dried in the sun. Alias: herba Sambuci Williamsii, herba Pileae Scriptae, rhizoma Panacis Japonici, rhizoma anemones Altaicae, herba Sambuci Williamsii, ramulus Sambuci Williamsii, herba Pileae Scriptae, herba Ardisiae Japonicae, radix Achyranthis bidentatae, herba Phyllanthi Urinariae, herba Pileae Scriptae, herba Lobeliae chinensis, radix Callicarpae Giraldii, radix seu caulis Sambuci Williamsii, radix Clematidis Cudraniani, herba Pileae Scriptae, herba Sambuci Williamsii, and bamboo tea. The glabrous sarcandra herb is mild in nature, bitter and pungent in taste and enters heart and liver meridians; the glabrous sarcandra herb has the effects of clearing away heat and toxic materials, cooling blood, promoting blood circulation, removing ecchymoses, dissipating blood stasis, dispelling wind, removing dampness and dredging collaterals. It is clinically used for treating blood-heat purpura, rheumatic arthralgia and traumatic injury. Numbness of limbs; fracture of the bone; dysmenorrhea in women; postpartum abdominal pain due to stasis; pneumonia; acute appendicitis; acute gastroenteritis; bacillary dysentery; cholecystitis (cholecystitis); abscesses; stomatitis; rheumatic arthralgia. The herba Pileae Scriptae tablet and herba Pileae Scriptae injection can be used for treating tumors such as digestive tract cancer, pancreatic cancer, and hepatocarcinoma.

CN101897740A (application number: 201010232919.5, Jiang Yao) relates to a glabrous sarcandra herb formula particle and a preparation method thereof, belonging to the preparation technology of traditional Chinese medicine formula particles. The glabrous sarcandra herb is extracted by water, concentrated and added with proper auxiliary materials to prepare formula particles, the content of active ingredients such as isofraxidin, general flavone and the like in the glabrous sarcandra herb formula particles is high, the quality is stable and controllable, and the prepared specification is that each 1-5 g of the formula particles is equivalent to 3-15 g of raw glabrous sarcandra herb; the content of isofraxidin in the glabrous sarcandra herb formula particles is not less than 0.6mg/g, and the content of total flavonoids is not less than 5.00 mg/g. Can meet the requirements of clinical treatment based on syndrome differentiation and addition and subtraction according to the syndrome, and is beneficial to flexible prescription of doctors. The invention changes the traditional glabrous sarcandra herb into granules, increases the stability of the invention, is easy to store and carry, has flexible formula, small dosage and convenient use.

CN108570113A (application number: 201710135706.2, Yao Da) relates to a preparation method of glabrous sarcandra herb extract residue polysaccharide, which is characterized by comprising the following steps: drying the glabrous sarcandra herb extract residue at 60 +/-10 ℃, and crushing into powder; adding deionized water with the weight at least 100 times that of the powder, heating, stirring and dissolving completely, and centrifuging to remove the precipitate to obtain a supernatant; adding absolute ethyl alcohol with at least 4 times of volume into the supernatant for alcohol precipitation, standing at 1-4 ℃ for at least 24 hours, and centrifuging to obtain precipitate; washing the precipitate with anhydrous ethanol, acetone and diethyl ether, and drying to obtain solid which is crude product of sarcandra glabra extract residue polysaccharide (SCRP); the polysaccharide content of the glabrous sarcandra herb extract residue polysaccharide crude product SCRP is more than 50 percent of the total solid weight; wherein, the glabrous sarcandra herb extract residue is a precipitate obtained by alcohol precipitation of a water extract of glabrous sarcandra herb extract. The polysaccharides can be used for preparing medicines for treating diabetes or alpha-glucosidase inhibitors. By adopting the invention, the resource utilization of the glabrous sarcandra herb extract residues can be realized.

CN1823857A (application No. 200510111642.X, Tianshikang) provides a preparation process of herba Pileae Scriptae extract, which comprises extracting crude extract powder of herba Pileae Scriptae with water, adding 10-30 times of water, heating to dissolve, filtering, concentrating the filtrate to obtain fluid extract with relative density of 1.15-1.30 at 60 deg.C, adding ethanol to make ethanol content reach 50-85%, standing, collecting supernatant, recovering ethanol, concentrating to obtain fluid extract with relative density of 1.30-1.40 at 60 deg.C, adding water to dilute to obtain fluid extract with relative density of 1.05-1.20, refrigerating, filtering, adding 0.5-1.5 times of water to dilute the filtrate, refrigerating, filtering, adding clarifier to the filtrate, refrigerating, filtering, concentrating the filtrate to obtain fluid extract with relative density of 1.15-1.30 at 60 deg.C, adding ethanol to make ethanol content reach 50-85%, standing, collecting supernatant, recovering ethanol, concentrating, drying at low temperature, obtaining glabrous sarcandra herb extract. The invention has simple process, and the produced glabrous sarcandra herb extract has high purity and good curative effect.

CN101612173A (application No. 200810029042.2, and Nanan) relates to a quality control method of herba Pileae Scriptae extract and its related preparations, which comprises establishing standard fingerprint of herba Pileae Scriptae extract by reversed-phase high performance liquid chromatography, including twelve chromatographic peaks, wherein the chemical structures of ten chromatographic peaks have been accurately identified, and the relative retention time of each chromatographic peak calculated by taking the chromatographic retention time of rosmarinic acid as 1 is 0.24 + -0.01 of neochlorogenic acid, 0.39 + -0.01 of chlorogenic acid, 0.41 + -0.01 of chlorogenic acid, 0.44 + -0.01 of cryptochlorogenic acid, 0.49 + -0.01 of caffeic acid, 0.56 + -0.02 of azinproxide, 0.70 + -0.02 of isofraxidin, 0.90 + -0.02 of rosmarinic acid-4-O-beta-D-glucoside, 0.3-O-beta-D-glucuronide, 0.97 + -0.02 of quercetin-3-O-beta-D-glucuronide, 0.00 of rosmarinic acid, 1.00 of beta-O-beta-D-glucuronide, 0.09 + -0.02 of caffeic acid, 1.15 plus or minus 0.02; similarity between the fingerprint of the test sample of the glabrous sarcandra herb extract and the preparation thereof and the standard fingerprint is not less than 0.65. In addition, a content determination method of various anti-inflammatory active ingredients is established by using a working curve method. The method can effectively control the product quality of herba Pileae Scriptae extract and its related preparations, and has good repeatability, high stability, excellent precision, and simple operation method.

CN103554290A (application No. 201310552026.2, Yao Da) discloses a refined glabrous sarcandra herb acidic polysaccharide SGP-2, which is characterized in that the content of the polysaccharide is more than 90 percent, and the number average molecular weight is 1000-2000 KDa; the monosaccharide comprises glucose, galactose, mannose, arabinose and galacturonic acid; the glycosidic bond type is α (1 → 4) galacturonic acid, α (1 → 4) methyl galacturonic acid, α (1 → 5) arabinose, α (1 → 4) mannose, β (1 → 6) glucose, β (1 → 3) galactose, α (1 → 4) glucose, β (1 → 4, 6) glucose, α (1 → 3, 6) mannose and α (1 → 4, 6) galactose. The invention provides application of a glabrous sarcandra herb acidic polysaccharide refined product SGP-2 in inhibiting activity of alpha-glucosidase and application of glabrous sarcandra herb acidic polysaccharide in preparing a medicament for treating diabetes. The invention also provides application of the glabrous sarcandra herb acidic polysaccharide refined SGP-2 in preparing antitumor drugs.

CN101664512A (application No. 200910177552.9, Tian Shi kang) provides a preparation method of a traditional Chinese medicine preparation containing glabrous sarcandra herb extract, which is characterized in that the following raw materials are weighed according to the parts by weight: 245 parts of glabrous sarcandra herb extract, 4-14 parts of aerosil and 2.5-10 parts of water, and the preparation method comprises the following steps: pulverizing herba Pileae Scriptae extract into fine powder, and sieving; pulverizing silica gel micropowder into fine powder, sieving, adding water, mixing with the above extract fine powder, granulating, directly tabletting, and coating.

The traditional Chinese medicine formula granule is a granule prepared by extracting and concentrating single traditional Chinese medicine decoction pieces and used for traditional Chinese medicine clinical formula. The product name and folk name of the single Chinese traditional medicine concentrated granule are non-decoction Chinese traditional medicine decoction pieces, new decoction pieces, refined decoction pieces, beverage type decoction pieces, scientific Chinese traditional medicine and the like. The traditional Chinese medicine prescription granule is a novel prescription medication with uniform specification, uniform dosage and uniform quality standard, which is processed by taking traditional Chinese medicine decoction pieces as raw materials through the production processes of extraction, separation, concentration, drying, granulation, packaging and the like.

The traditional Chinese medicine formula particle is an innovation of the traditional Chinese medicine, and is a powder or granular preparation which is prepared by taking a single traditional Chinese medicine decoction piece which meets the processing specification as a raw material and extracting and refining the raw material by a modern process. Has the advantages of cleanness, convenience for use, smallness, benefit, essence and stability, no need of decoction, convenient taking, quick response, advanced process, easy storage and convenient quality control, and meets the requirements of modern society on medicaments.

Conceptually, the single Chinese medicine formula granule is a pure Chinese medicine product series which is prepared by taking traditional Chinese medicine decoction pieces which meet processing specifications as raw materials, extracting, concentrating, separating, drying, granulating, packaging and refining by modern pharmaceutical technology. The traditional Chinese medicine decoction pieces have the advantages of ensuring all characteristics of the original traditional Chinese medicine decoction pieces, satisfying the requirements of doctors for treatment based on syndrome differentiation, having strong medicine property and high medicine effect when added or subtracted according to the symptoms, having no need of decoction, direct taking with water, small dosage, rapid action, complete components, exact curative effect, safety, sanitation, convenient carrying and storage, easy modulation, suitability for industrial production and the like.

The active ingredients, the properties and the tastes, the channel tropism, the main treatment and the efficacy of the traditional Chinese medicine formula granules are completely consistent with those of the traditional Chinese medicine decoction pieces, the characteristics of the traditional Chinese medicine decoction pieces are kept, the characteristics of traditional monarch, minister, assistant and guide of the traditional Chinese medicine and the characteristics of dialectical treatment and flexible addition and subtraction can be ensured, the traditional Chinese medicine formula granules are superior to Chinese patent medicines, the trouble of traditional decoction of patients is avoided, and simultaneously, the traditional Chinese medicine formula granules can be flexibly taken with single granules, are sanitary and effective.

The advantages of the traditional Chinese medicine formula granule are very remarkable. The traditional Chinese medicine formula granules are convenient to use and can replace traditional decoction pieces to be used for clinical syndrome differentiation treatment by traditional Chinese medical doctors; the medicine is prepared into medicinal granules by warm boiled water when in use without being decocted; the small dose is finely packaged, the concentration of the infusion can be automatically adjusted, and the administration dose is small; the unit medicine has light weight, small volume and convenient storage and transportation; the composite aluminum foil is packaged, and is convenient to carry and store; safe and sanitary, moisture-proof and moth-proof, and has long shelf life; the medicine name is printed clearly, the formula is clean and sanitary, and the traditional Chinese medicine management is enhanced. The Chinese medicinal granule is safe to use, and the raw materials are processed traditional Chinese medicinal decoction pieces which are strictly controlled in quality; extracting with modern pharmaceutical technology, separating, concentrating, drying, granulating, and packaging; uniform specification, consistent standard, and definite and stable curative effect. The effectiveness of the traditional Chinese medicine formula granules can be ensured, and the traditional Chinese medicine formula granules have the same effective components, properties, flavors, channels and main treatment effects as the traditional decoction pieces; the effective components in unit mass are several times higher than those in the traditional decoction pieces; strong medicinal property, high medicinal effect and quick action.

The general administration method of the traditional Chinese medicine formula granule comprises the steps of pouring each bag of medicine in one dose of medicine (daily dose, and possibly respective formula granules of a plurality of medicines) into a same cup, soaking the medicine in a small amount of warm water at proper time, then dissolving the medicine in a proper amount of boiled water, stirring and uniformly mixing the medicine to ensure that the medicine is fully dissolved, and taking the medicine by times according to the medical advice, wherein the taking time is selected according to the different effects of the prescription and before or after meal according to the medical advice.

For the subject of traditional Chinese medicine and pharmacology, the popularization of single traditional Chinese medicine formula granules (namely decoction-free traditional Chinese medicine decoction pieces) is a historical event. There are several marked times in the history of traditional Chinese medicine development: the theory and practice foundation of traditional Chinese medicine is laid in the era of the internal classic; in the age of Zhang Zhongjing, the traditional Chinese medical science and medical science ideas of treatment based on syndrome differentiation and addition and subtraction with syndromes are established by the classic medical books represented by Shanghai treatise on Cold-induced diseases, and the later Wen Bing theory, the four people of Jinyuan and the like are derived on the basis of treatment based on syndrome differentiation;

from the end of the 20 th century to the beginning of the 21 st century, the development of traditional Chinese medicine has entered a new historical period with modernization and internationalization as a theme, and it can be said that the realization of modernization and internationalization of traditional Chinese medicine is an epoch-making sign in the development history of traditional Chinese medicine. In this period, what we need to do and what we can do is to advance the standardization and objectification of traditional Chinese medicine. The popularization of decoction-free traditional Chinese medicine decoction pieces is the first step of realizing the standardization and objectification of traditional Chinese medicines, and the development of the theory and practice of traditional Chinese medicines driven by the decoction-free traditional Chinese medicine decoction pieces is bound to occupy an important historical position in the development history of traditional Chinese medicines. For the majority of doctors and patients, the popularization of the decoction-free traditional Chinese medicine decoction pieces provides more efficient, safe, stable, convenient, rapid, cheap and scientific health-care treatment means for doctors and patients, and leads the traditional Chinese medicine to appear in the front of the world in a brand-new image.

In the clinical observation report of the decoction-free Chinese medicine combined by the national Bureau of TCM and the Bureau of TCM of Guangdong province, 2 ten thousand prescriptions were analyzed, wherein the decoction-free Chinese medicine can be applied to the specialties suitable for the application of the traditional Chinese medicine decoction pieces, and the instant taking property of the decoction-free Chinese medicine promotes the application of important compound (single medicine) in emergency medicine. In terms of the using method, the decoction-free traditional Chinese medicine can be taken orally, and can also be used for retention enema, fumigation, washing, wet dressing, external application, atomization and the like.

Although the glabrous sarcandra herb is clinically applied to single-prescription preparations such as glabrous sarcandra herb tablets, Xuekang oral liquid and the like, the glabrous sarcandra herb is also applied to a plurality of Chinese patent medicines and proved preparations, and the preparation of the glabrous sarcandra herb into the Chinese medicine formula granules is beneficial to facilitating the treatment of diseases in the traditional Chinese medicine, especially in the period of occurrence of large-scale public health events. Although the existing glabrous sarcandra herb tablets are single-prescription preparations, the single-dose volume of the tablets is large due to the addition of a large amount of auxiliary materials, so that the tablets are not suitable to be directly used as prescription granules required to be used together with other traditional Chinese medicines, otherwise, the tablets cannot be taken due to the fact that the single-dose is too large when the tablets are used together with other traditional Chinese medicines. It can be seen that the auxiliary materials should be added as little as possible when preparing the formula granule, however, the glabrous sarcandra herb extract has the characteristic of difficult forming of the typical traditional Chinese medicine extract, for example, when no or little auxiliary materials are added, the properties of one or more aspects of flowability, solubility and the like of the prepared formula granule have great challenges.

Therefore, it is still desired in the art to provide glabrous sarcandra herb formulation granules with excellent properties for clinical application.

Disclosure of Invention

The invention aims to provide glabrous sarcandra herb formula granules for clinical application. The inventor finds that the glabrous sarcandra herb formula particles prepared by the method of the invention show excellent effects. The present invention has been completed based on this finding.

In the present invention, glabrous Sarcandra herb is used as a herb material, and unless otherwise specified, the glabrous Sarcandra herb is a dried whole herb of Sarcandra glabra (Thunb.) Nakai which is a plant of Chloranthaceae.

To this end, the present invention provides in a first aspect a process for preparing a glabrous sarcandra herb granule comprising the steps of:

(1) weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water with the weight 6-10 times that of the medicinal material for the first time, decocting for 0.5-2 hours, and filtering to obtain filtrate for later use; adding 5-7 times of water for the second time and the third time respectively, decocting for 0.5-2 hours each time, and filtering; mixing the three filtrates, mixing, concentrating under reduced pressure, and spray drying to water content of less than 9%, such as less than 7%, such as less than 5% to obtain powdered dry extract;

(2) and (3) uniformly mixing 1 part by weight of dry paste with 0.1-0.2 part by weight of dextrin, and performing dry granulation on a dry granulator to obtain the glabrous sarcandra herb formula granules.

The method according to the first aspect of the present invention, wherein the glabrous Sarcandra is dried whole herb of Sarcandra glabra (Thunb.) Nakai, a plant belonging to chloranthaceae.

The process according to the first aspect of the present invention, wherein in the step (1), when the concentration under reduced pressure is carried out, the concentration under reduced pressure is carried out under the conditions: the vacuum degree is-0.04 MPa to-0.08 MPa, and the temperature is 55 ℃ to 65 ℃. For example, the conditions for concentration under reduced pressure are: the vacuum degree is-0.07 MPa, and the temperature is 60 ℃.

The method according to the first aspect of the invention, wherein in the step (1), the clear paste obtained by concentrating under reduced pressure has a relative density of 1.10 to 1.15(60 ℃).

The method according to the first aspect of the present invention, wherein in the step (1), the decoction is filtered twice using a 200-mesh sieve.

The method according to the first aspect of the present invention, wherein in the step (1), the temperature of the inlet air of the spray dryer during spray drying is 170 to 175 ℃.

The process according to the first aspect of the present invention, wherein in step (1), the water content of the dried paste obtained by spray drying is less than 4%, for example, less than 3%.

The method according to the first aspect of the present invention, wherein in step (1), the dried paste obtained by spray drying in the form of powder can pass through a 80-mesh sieve.

The method according to the first aspect of the present invention, wherein in the step (2), when the dry granulation is performed on the dry granulator, the pinch roller spacing is set to 0.3 to 0.5mm, for example, the pinch roller spacing is set to 0.4 mm.

The method according to the first aspect of the present invention, further comprising the following step (3) of preparing the standard particle:

(3) precisely weighing 500g of glabrous sarcandra herb, decocting for three times, adding 8 times of water for the first time, decocting for 1 hour, and filtering to obtain filtrate for later use; adding 6 times of water for the second time, and decocting for 1 hour; adding 6 times of water for the third time, and decocting for 1 hour; filtering, mixing the three filtrates, and mixing; and (3) concentrating under reduced pressure until the material feeding amount: concentrating to obtain fluid extract with volume ratio of 1:2.5 (g: ml), freeze drying to water content below 2% to obtain standard granule;

the method according to the first aspect of the present invention, further comprising the following step (4):

(4) and (3) measuring the content of the index substances of the standard granules obtained in the step (3) and the glabrous sarcandra herb formula granules obtained in the step (2), and calculating the amount of the glabrous sarcandra herb medicine material equivalent to each 1g of the glabrous sarcandra herb formula granules obtained in the step (2) by combining the content of the index substances in the two granules and the material feeding amount in the step (3).

The method according to the first aspect of the present invention, further comprising the step (5):

(5) and (4) calculating the amount of the particles subpackaged in each bag according to the weight of the medicinal materials converted from the glabrous sarcandra herb formula particles obtained in the step (4), and subpackaging the glabrous sarcandra herb formula particles into packaging bags to obtain the packaged glabrous sarcandra herb formula particles.

The method according to the first aspect of the present invention, wherein in the step (4), the indicator substance is isofraxidin.

The method according to the first aspect of the present invention, wherein in step (4), the content of the index substance isofraxidin is determined using the following method:

performing high performance liquid chromatography measurement according to China pharmacopoeia 2020 edition four-part general rule 0512;

chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile (containing 0.1% formic acid) is used as a mobile phase A, 0.1% formic acid is used as a mobile phase B, and gradient elution is carried out according to the specification in the following table; the detection wavelength was 330 nm. The number of theoretical plates is not less than 5000 according to the peak of isofraxidin and the peak of rosmarinic acid respectively;

time (minutes)	Mobile phase A (%)	Mobile phase B (%)
			0-10	20	80
10-25	20->35	80->65
			25-26	35->100	65->0
26-30	100	0

Preparation of control solutions: respectively taking a proper amount of isofraxidin and a rosmarinic acid reference substance, precisely weighing, and adding 60% methanol to prepare a mixed solution containing 15 mu g of isofraxidin and 25 mu g of rosmarinic acid per 1ml to obtain the product;

preparation of a test solution: weighing about 0.25g of the powder (sieved by a third sieve), precisely weighing, placing in a conical flask with a plug, adding 50ml of 60% methanol, weighing, ultrasonically treating (with the power of 250W and the frequency of 40kHz) for 30 minutes, taking out, cooling, weighing again, supplementing the weight loss by 60% methanol, shaking up, filtering, and taking the subsequent filtrate to obtain the final product;

the determination method comprises the following steps: respectively and precisely sucking 10 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, measuring, and calculating the content of isofraxidin in the standard granules and the formula granules.

The method according to the first aspect of the present invention, wherein in step (5), the packaged glabrous sarcandra herb formulation comprises formulation granules in each bag in an amount corresponding to 0.5-20 g, such as 1-15 g, such as 1-10 g, such as 1-8 g, such as 1-5 g. As is known, the amount of the Chinese herbal medicine packaged in each bag is small, so that the Chinese herbal medicine can be more widely applied to Chinese herbal medicine prescriptions with different addition amounts of the glabrous sarcandra herb, for example, the Chinese herbal medicine prescription containing 1g, 2g, 3g or 4g of the glabrous sarcandra herb in each dose of Chinese herbal medicine prescription can be packaged by using 1g of the glabrous sarcandra herb/bag of formula granules. However, similarly, larger packaging quantities may be suitable.

The method according to the first aspect of the present invention, wherein before the spray-drying in the step (1), sodium starch phosphate and calcium alginate are further added to the fluid extract obtained by the concentration under reduced pressure.

According to the method of the first aspect of the invention, in the step (1), the weight ratio of the added amount of the sodium starch phosphate to the solid content of the clear paste is 0.4-0.5: 100.

According to the method of the first aspect of the invention, in the step (1), the weight ratio of the addition amount of the calcium alginate to the solid content of the filtrate is 0.2-0.3: 100. It has been surprisingly found that when small amounts of sodium starch phosphate and calcium alginate are added simultaneously to the fluid extract to be spray-dried, excellent technical effects can be imparted to the present formulation granules.

In the invention, the solid matter of the clear paste refers to the solid matter remained after the clear paste is dried and the solvent is removed so that the moisture content is less than 2%.

Further, the second aspect of the present invention provides a glabrous sarcandra herb granule, which is prepared by a method comprising the following steps:

(1) weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water with the weight 6-10 times that of the medicinal material for the first time, decocting for 0.5-2 hours, and filtering to obtain filtrate for later use; adding 5-7 times of water for the second time and the third time respectively, decocting for 0.5-2 hours each time, and filtering; mixing the three filtrates, mixing, concentrating under reduced pressure, and spray drying to water content of less than 9%, such as less than 7%, such as less than 5%, to obtain powdered dry extract;

The glabrous Sarcandra herb formulation according to the second aspect of the present invention, wherein the glabrous Sarcandra herb is dried whole herb of Sarcandra glabra (Thunb.) Nakai of chloranthaceae.

The glabrous sarcandra herb formulation granules according to the second aspect of the present invention, wherein in the step (1), when the concentration under reduced pressure is performed, the concentration under reduced pressure is performed under the conditions of: the vacuum degree is-0.04 MPa to-0.08 MPa, and the temperature is 55 ℃ to 65 ℃. For example, the conditions for concentration under reduced pressure are: the vacuum degree is-0.07 MPa, and the temperature is 60 ℃.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein in the step (1), the clear paste obtained by concentrating under reduced pressure has a relative density of 1.10 to 1.15(60 ℃).

The glabrous sarcandra herb formulation granules according to the second aspect of the present invention, wherein in the step (1), the decoction is filtered twice using a 200 mesh sieve.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein in the step (1), the temperature of the inlet air of the spray dryer during spray drying is 170 to 175 ℃.

The glabrous sarcandra herb granules according to the second aspect of the present invention, wherein in the step (1), the moisture content of the dried paste obtained by spray drying is less than 4%, for example, the moisture content is less than 3%.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein in step (1), the dry paste obtained by spray drying in the form of powder may pass through a 80-mesh sieve.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein in the step (2), when dry granulation is performed on a dry granulator, the interval between the pressing wheels is set to 0.3 to 0.5mm, for example, the interval between the pressing wheels is set to 0.4 mm.

The glabrous sarcandra herb granules according to the second aspect of the present invention further comprise the following step (3) of preparing standard granules:

the glabrous sarcandra herb formula particle according to the second aspect of the present invention further comprises the following step (4):

The glabrous sarcandra herb formula particle according to the second aspect of the present invention further comprises the following step (5):

(5) and (5) calculating the amount of the granules subpackaged in each bag according to the converted medicinal material weight of the glabrous sarcandra herb formula granules obtained in the step (4), and subpackaging the glabrous sarcandra herb formula granules into packaging bags to obtain the subpackaged glabrous sarcandra herb formula granules.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein the indicator substance is isofraxidin in step (4) of the preparation step.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein in the step (4) of the preparation step, the content of isofraxidin as an index substance is determined using the following method:

the determination method comprises the following steps: respectively and precisely sucking 10ul of each of the reference solution and the test solution, injecting into a liquid chromatograph, measuring, and calculating the content of isofraxidin in the standard granules and the formula granules.

According to the glabrous sarcandra herb formula granule of the second aspect of the present invention, in the step (5) of the preparation step, the packaged glabrous sarcandra herb formula granule contains formula granules in an amount of 0.5-20 g, such as 1-15 g, such as 1-10 g, such as 1-8 g, such as 1-5 g, of glabrous sarcandra herb in each bag. As is known, the amount of the Chinese herbal medicine packaged in each bag is small, so that the Chinese herbal medicine can be more widely applied to Chinese herbal medicine prescriptions with different addition amounts of the glabrous sarcandra herb, for example, the Chinese herbal medicine prescription containing 1g, 2g, 3g or 4g of the glabrous sarcandra herb in each dose of Chinese herbal medicine prescription can be packaged by using 1g of the glabrous sarcandra herb/bag of formula granules. However, similarly, larger packaging quantities may be suitable.

The glabrous sarcandra herb formulation granule according to the second aspect of the present invention, wherein before the spray drying in step (1), sodium starch phosphate and calcium alginate are further added to the fluid extract obtained by concentration under reduced pressure.

According to the glabrous sarcandra herb formula particle of the second aspect of the invention, in the step (1), the weight ratio of the added amount of sodium starch phosphate to the solid content of the clear paste is 0.4-0.5: 100.

According to the glabrous sarcandra herb formula particle of the second aspect of the present invention, in the step (1), the weight ratio of the added amount of calcium alginate to the solid content of the filtrate is 0.2-0.3: 100. it has been surprisingly found that when small amounts of sodium starch phosphate and calcium alginate are added simultaneously to the fluid extract to be spray-dried, excellent technical effects can be imparted to the present formulation granules.

In a third aspect, the invention provides the use of the glabrous sarcandra herb formula particle of the second aspect of the invention in preparing a medicament for clearing heat and removing toxicity, and reducing swelling and resolving masses.

In a third aspect, the invention provides the use of the glabrous sarcandra herb formula particle of the second aspect of the invention in preparing a medicament for treating pneumonia, appendicitis and cellulitis due to excessive heat-toxin.

In a third aspect, the present invention provides the use of the glabrous sarcandra herb formulation granule of the second aspect in the preparation of a medicament for the adjuvant treatment of cancer.

In a fourth aspect, the present invention provides a pharmaceutical composition comprising a glabrous sarcandra herb formulation according to any one of the embodiments of the second aspect of the present invention and optionally a pharmaceutically acceptable carrier.

The pharmaceutical composition according to the fourth aspect of the present invention, which is in the form of a formulation for oral or injectable administration. In one embodiment, the pharmaceutical composition is in the form of tablets, capsules, granules, pills, oral liquids, injections (water and/or powder) and the like.

Any feature of any aspect of the invention or any embodiment of any aspect thereof is equally applicable to any other embodiment or any embodiment of any other aspect thereof, provided that they are not mutually inconsistent, although appropriate modifications to the respective features may be made as necessary when applicable to each other. Various aspects and features of the disclosure are described further below.

All documents cited herein are incorporated herein by reference in their entirety and to the extent they do not conform to the teachings of the present invention, the statements made therein shall control. Further, the various terms and phrases used herein have the ordinary meaning as is known to those skilled in the art, and even though such terms and phrases are intended to be described or explained in greater detail herein, reference is made to the term and phrase as being inconsistent with the known meaning and meaning as is accorded to such meaning throughout this disclosure.

Herba Pileae Scriptae is dry whole plant of sarcandra glabra (Thunb.) nakai of Chloranthaceae. Collected in summer and autumn, removed of impurities and dried in the sun. Alias: herba Sambuci Williamsii, herba Pileae Scriptae, rhizoma Panacis Japonici, rhizoma anemones Altaicae, herba Sambuci Williamsii, ramulus Sambuci Williamsii, herba Pileae Scriptae, herba Ardisiae Japonicae, radix Achyranthis bidentatae, herba Phyllanthi Urinariae, herba Pileae Scriptae, herba Lobeliae chinensis, radix Callicarpae Giraldii, radix seu caulis Sambuci Williamsii, radix Clematidis Cudraniani, herba Pileae Scriptae, herba Sambuci Williamsii, and bamboo tea. The main functions are antibiosis, anti-inflammation, blood cooling, heat clearing and detoxifying, wind dispelling, collateral dredging, blood circulation promoting and stasis dissipating. Can be used for treating pneumonia, appendicitis, and cellulitis due to excessive toxic heat; and adjuvant treatment of rheumatalgia, traumatic injury, and tumor.

Glabrous sarcandra herb is bitter and pungent in leaf and neutral in nature, and enters heart and liver meridians. Has the effects of clearing away heat and toxic materials, cooling blood, promoting blood circulation, removing speckle, dispelling blood stasis, dispelling pathogenic wind, removing dampness, and dredging meridians. Can be used for treating blood heat purpura, rheumatalgia, and traumatic injury. Numbness of limbs; fracture of the bone; dysmenorrhea in women; postpartum abdominal pain due to stasis; pneumonia; acute appendicitis; acute gastroenteritis; bacillary dysentery; cholecystitis (cholecystitis); abscesses; stomatitis; rheumatic arthralgia. The herba Pileae Scriptae tablet and herba Pileae Scriptae injection can be used for treating tumors such as digestive tract cancer, pancreatic cancer, and hepatocarcinoma. The Deng Pan literature (Deng Pan, et al, research and discussion of glabrous sarcandra herb extraction process, Chinese medicine science, 2019 (05): 82-85) develops deep research on the industrialized production of glabrous sarcandra herb extraction and optimizes the glabrous sarcandra herb extraction process, wherein the influence of each factor on the extraction process of glabrous sarcandra herb parts, decoction water pH, soaking temperature and soaking time is investigated by adopting a method combining a single-factor test and an orthogonal test; the glabrous sarcandra herb alcohol precipitation process is researched, a single-factor gradient test is adopted, and the alcohol precipitation temperature and the concentration of added ethanol are optimized. The result is that the content of isofraxidin in the water decoction concentrated solution prepared from the glabrous sarcandra rhizome is far higher than that of glabrous sarcandra leaf, and the yield of the water decoction concentrated solution obtained by decocting the glabrous sarcandra leaf is higher than that of the glabrous sarcandra rhizome; the optimal process for the glabrous sarcandra herb decoction process comprises extracting the glabrous sarcandra herb at the pH of 6.0, and soaking at the temperature of 60 ℃ for 60 min; the higher the alcohol precipitation temperature is, the higher the yield of the glabrous sarcandra herb alcohol precipitation process is, and the total content of isofraxidin in the glabrous sarcandra herb extract after alcohol precipitation and the concentration of added ethanol are in parabolic distribution, wherein the total content of isofraxidin in the glabrous sarcandra herb extract obtained by using 85% ethanol is the lowest. And (4) conclusion: the experiment optimizes the extraction process of herba Pileae Scriptae, and can guide the industrialized production of herba Pileae Scriptae. However, the process of this document is not suitable for preparing glabrous sarcandra herb formulation granules.

The glabrous sarcandra herb formula granules prepared by the method have less auxiliary material consumption and can show one or more excellent effects.

Detailed Description

The present invention will be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and modifications may be made to the invention without departing from the spirit and scope of the invention. The present invention has been described generally and/or specifically with respect to materials used in testing and testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible. The following examples further illustrate the invention without limiting it.

The following preparation steps are given for the purpose of illustration and are based on the comparative nature of the respective examples and the person skilled in the art is fully enabled to generalize from the prior knowledge the process of the invention for preparing the products of the invention.

In the specific example herein, when the material is dosed in units of parts by weight, not less than 20kg of glabrous sarcandra herb is dosed per batch. Some typical equipment and equipment used in the present invention for preparing standard granules and formula granules are as follows: a rotary evaporator (RE-5205, Shanghai Yangrong), a vacuum pump (SHB-III, Zhengzhou great wall), a vacuum freeze dryer (LC-2010CHT, Songyuan Huaxing), a low-temperature cold trap (DWJ-3, Songyuan Huaxing), a moisture tester (MB23, Onhause, Changzhou), and a high performance liquid chromatograph (LC-2010CHT, Shimadzu, Japan); an extraction tank (300L, 500L, zhejiang jinan), a double-effect external circulation evaporator (ZII-300, zhejiang jinan), a vacuum belt dryer (DVD205, wenzhou jinbang), a three-dimensional mixer (KSH-50, kunjieyucheng), a repose angle tester (FT-104B, north-south of wuhan), a multifunctional extraction tank (300L, zhejiang jinan), a single-effect alcohol recovery evaporator (JWZ, zhejiang jinan), a spray dryer (OPD-8, shanghai dachuan original), a dry granulator (GL-5C, zhejiang mingtian), a full-automatic granule packaging machine (DXDK80D, beijing taide).

In the dry granulation process for preparing formulation granules of the following specific example of the present invention, the materials to be granulated are mixed for 20 minutes, and dry granulation is performed under the conditions of a feeding speed of 26-30 rpm, a pressing wheel rotating speed of 2rpm, and a pressing wheel interval of 0.3-0.5 mm, wherein the obtained granule size cannot pass through a first sieve or a fourth sieve, and the granule size cannot exceed 10%.

In the spray drying process for preparing the formulation particles of the embodiments of the present invention, spray drying is performed in a spray drying apparatus at an inlet air temperature of 170 to 175 ℃ and an inlet liquid speed of 13 to 15 rpm.

Example 1: preparing glabrous sarcandra herb standard granules

Precisely weighing 500g of glabrous sarcandra herb, decocting for three times, adding 8 times of water for the first time, decocting for 1 hour, and filtering to obtain filtrate for later use; adding 6 times of water for the second time, and decocting for 1 hour; adding 6 times of water for the third time, and decocting for 1 hour; filtering, mixing the three filtrates, and mixing; concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 65 ℃) until the material charging amount: the concentrated solution is clear paste with the volume ratio of 1:2.5 (g: ml), and the clear paste is frozen and dried (the pre-freezing temperature is-38 to-45 ℃, the drying cold hydrazine temperature is-60 to-70 ℃, and the vacuum degree is less than 100 Pa; as a conventional pharmaceutical process, other process parameters are feasible as long as the moisture can be reduced to the target range) to ensure that the moisture content is less than 2 percent, and standard granules are obtained. The content of isofraxidin in the standard particles was determined.

Example 11: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water with the weight 8 times of that of the medicinal materials for the first time, decocting for 1 hour, and filtering to obtain filtrate for later use; adding 6 times of water for the second time, decocting for 1 hour, and filtering to obtain filtrate; adding 6 times of water for the third time, decocting for 1 hour, and filtering to obtain filtrate; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.13(60 deg.C)), spray drying (air inlet temperature 170-175 deg.C) until water content is lower than 4% (2.43%), and making into powdered dry extract (capable of passing through 80 mesh sieve);

(2) mixing 1 weight part of dry extract with 0.15 weight part of dextrin, and performing dry granulation on a dry granulator (extrusion crushing type dry granulator with a pressure wheel interval of 0.4mm) to obtain herba Pileae Scriptae granule;

(3) measuring the content of isofraxidin serving as an index substance of the standard granules obtained in example 1 and the glabrous sarcandra herb formula granules obtained in step (2), and calculating the amount of glabrous sarcandra herb equivalent to each 1g of glabrous sarcandra herb formula granules obtained in step (2) by combining the content of the index substances in the two granules and the material feeding amount in step (1);

(4) calculating the amount of the particles packed in each bag according to the weight of the medicinal materials converted from the glabrous sarcandra herb formula particles obtained in the step (3), and packing the glabrous sarcandra herb formula particles in packing bags to obtain the packed glabrous sarcandra herb formula particles (each bag is equivalent to 2g (or 1g, 3g, 4g, 5g, 7.5g, 10g or other amount) of glabrous sarcandra herb medicinal materials.

In the various tests of the present invention, the method for determining the content of isofraxidin, the indicator substance, of the standard and formulation granules, is as follows, unless otherwise specified:

The same batch was used for all the experiments in examples 1, 11 to 13, 21 to 23 and 31 to 33. It was determined that the content of isofraxidin in the standard granules prepared from 10g equivalent of crude drug in example 1 was 2.642mg, and that the content of isofraxidin in the granules prepared from 10g equivalent of crude drug in examples 11 to 13, examples 21 to 23, and examples 31 to 33 was 2.463 to 2.814mg, for example, 2.627mg in example 11, 2.585mg in example 21, and 2.542.34mg in example 311). These results show that the formulation granules prepared by the various methods of the present invention are substantially equivalent to the standard granules in terms of the indicative substance contained therein.

Example 12: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water 7 times the weight of the medicinal materials for the first time, decocting for 1.5 hours, and filtering to obtain filtrate for later use; adding 7 times of water for the second time, decocting for 0.75 h, filtering, and keeping the filtrate for later use; adding 5 times of water for the third time, decocting for 1.5 hours, filtering, and keeping the filtrate for later use; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.10(60 deg.C)), spray drying (air inlet temperature 170-175 deg.C) until water content is lower than 4% (2.26%), to obtain powdered dry extract (capable of passing through 80 mesh sieve);

(2) mixing 1 weight part of dry extract with 0.2 weight part of dextrin, and performing dry granulation on a dry granulator (extrusion crushing type dry granulator with a pressure roller interval of 0.4mm) to obtain herba Pileae Scriptae granule;

Example 13: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water 9 times the weight of the medicinal materials for the first time, decocting for 0.75 hour, and filtering to obtain filtrate for later use; adding 5 times of water for the second time, decocting for 1.5 hours, filtering, and keeping the filtrate for later use; adding 7 times of water for the third time, decocting for 0.75 h, filtering, and keeping the filtrate for later use; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.15(60 deg.C)), spray drying (air inlet temperature 170-175 deg.C) until water content is lower than 4% (2.07%), and making into powdered dry extract (capable of passing through 80 mesh sieve);

(2) mixing 1 weight part of dry extract with 0.1 weight part of dextrin, and performing dry granulation on a dry granulator (extrusion crushing type dry granulator with a pressure roller interval of 0.4mm) to obtain herba Pileae Scriptae granule;

Example 21: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water with the weight 8 times of that of the medicinal materials for the first time, decocting for 1 hour, and filtering to obtain filtrate for later use; adding 6 times of water for the second time, decocting for 1 hour, and filtering to obtain filtrate; adding 6 times of water for the third time, decocting for 1 hour, and filtering to obtain filtrate; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.13(60 deg.C)), adding sodium starch phosphate (weight ratio of sodium starch phosphate to solid of fluid extract is 0.45: 100) and calcium alginate (weight ratio of calcium starch phosphate to solid of fluid extract is 0.25: 100), mixing, spray drying (air inlet temperature 170-175 deg.C) to water content of less than 4% (2.43%), and making into powdered dry extract (capable of passing through 80 mesh sieve);

(2) mixing 1 weight part of dry extract with 0.15 weight part of dextrin uniformly, and performing dry granulation on a dry granulator (extrusion crushing type dry granulator with the distance between pressing wheels being 0.4mm) to obtain herba Pileae Scriptae granules;

Example 22: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water 7 times the weight of the medicinal materials for the first time, decocting for 1.5 hours, and filtering to obtain filtrate for later use; adding 7 times of water for the second time, decocting for 0.75 hour, filtering, and keeping the filtrate for later use; adding 5 times of water for the third time, decocting for 1.5 hours, filtering, and keeping the filtrate for later use; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.10(60 deg.C)), adding sodium starch phosphate (weight ratio of sodium starch phosphate to solid of fluid extract is 0.45: 100) and calcium alginate (weight ratio of calcium starch phosphate to solid of fluid extract is 0.25: 100), mixing, spray drying (air inlet temperature 170-175 deg.C) to water content of less than 4% (2.26%), and making into powdered dry extract (capable of passing through 80 mesh sieve);

Example 23: preparation of glabrous sarcandra herb formula granules

(1) Weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water 9 times the weight of the medicinal materials for the first time, decocting for 0.75 hour, and filtering to obtain filtrate for later use; adding 5 times of water for the second time, decocting for 1.5 hours, filtering, and keeping the filtrate for later use; adding 7 times of water for the third time, decocting for 0.75 h, filtering, and keeping the filtrate for later use; mixing the three filtrates, mixing, concentrating under reduced pressure (vacuum degree-0.07 MPa, temperature 60 deg.C, concentrating to relative density of 1.15(60 deg.C)), adding sodium starch phosphate (weight ratio of sodium starch phosphate to solid of fluid extract is 0.45: 100) and calcium alginate (weight ratio of calcium starch phosphate to solid of fluid extract is 0.25: 100), mixing, spray drying (air inlet temperature 170-175 deg.C) to water content of less than 4% (2.07%), and making into powdered dry extract (capable of passing through 80 mesh sieve);

Example 31: three batches of granules were prepared by following the procedure of examples 21 to 23 except that sodium starch phosphate was not added (example 311, example 312, example 313, respectively).

Example 32: three batches of formula granules (example 321, example 322 and example 323, respectively) were prepared by referring to the methods of examples 21-23 except that no calcium alginate was added.

Example 33: glabrous sarcandra formulation granules were prepared by referring to the methods of examples 21-23 except that sodium starch phosphate and calcium alginate were not added before spray drying, but were added with dextrin before granulation to give three batches of formulation granules (which may be referred to as example 331, example 332, example 333, respectively).

Test example 1: spray drying Condition inspection

In the above examples 11 to 33, the process conditions in the spray drying process were examined, and as a result: all batches of materials have no wall sticking phenomenon and can be collected into loose dry paste powder, which shows that the spray drying process is used for drying the materials, and the process performance is excellent.

Test example 2: investigation of Dry granulation Process

The dry granulation process is a new granulation technique that has emerged in recent years. The dry granulation process has the advantages that after a proper amount of auxiliary materials are added into the dry traditional Chinese medicine extract powder, the dosage of the auxiliary materials is small, direct granulation can be realized, the processes of wetting, mixing, granulating, drying and the like are not needed, the process is simple and convenient, and the quality of the traditional Chinese medicine can be effectively ensured, so the dry granulation process is selected to prepare the formula granules.

In the above examples 11 to 33, the process conditions during the dry granulation process were examined, and as a result: the granules obtained in all batches have moderate hardness, uniform size and no color difference, the materials are stripped in the granulating process and do not stick to wheels, and the powder falling is less in examples 11 to 33.

Test example 3: flowability study of the formulation granules

The flowability of solid materials, in particular particles, is generally characterized by an angle of repose, which is less than 40 °, in particular less than 35 °, indicating good flowability of the material, and which is greater than 40 °, in particular greater than 45 °, indicating poor flowability of the material. Good particle flowability is often beneficial for subsequent processing of the particles, such as dispensing.

In the present invention, unless otherwise specified, the method for measuring the parameter "angle of repose" is described in "pharmacy" of textbook (edited by Ju Miud of the Prostion of Zhu, third edition, published by the people's health Press, 3 rd edition 4 th 1996 month, ISBN 7-117-. It should be noted that there are many ways to characterize or determine the angle of repose of the granules/powders of the composition of the present invention, for example, there are other methods of determination in the third edition of the textbook "pharmacy" written by xi Zi. In the context of the present invention, the method for characterizing or determining the angle of repose of the granules/powders of the composition according to the invention is carried out using the "fixed hopper method" described above, if not otherwise specified.

The angle of repose of the granules of the formulations prepared according to the invention was determined and the results: the results of examples 11-13, 21-23, and 31-33, in which the angle of repose of the granules was within the range of 32-37 °, for example, the angle of repose of the granules of examples 11 and 21 was 36.3 ° and 33.4 °, respectively, show that the flowability of the granules obtained from different formulations or processes was good.

Test example 4: moisture absorption and solubility considerations for formulation granules

In the first part of 'Chinese pharmacopoeia' of 2020 edition, the medicinal materials glabrous sarcandra herb, glabrous sarcandra herb extract, glabrous sarcandra herb tablet and Xuekang oral liquid are collected.

The preparation method of the glabrous sarcandra herb extract recorded in pharmacopoeia comprises the following steps: decocting herba Pileae Scriptae in water for three times, each for 1 hr, mixing decoctions, filtering, concentrating the filtrate to obtain soft extract, and drying at 85 deg.C under reduced pressure.

The preparation method of the glabrous sarcandra herb extract has no essential difference from the method for preparing the formula granules in the embodiment 11 of the invention.

The glabrous sarcandra herb extract is not directly applied to clinic, but is industrially used for preparing preparation products such as glabrous sarcandra herb tablets, Xuekang oral liquid and the like, the preparation products are finally applied to clinic, so the glabrous sarcandra herb extract is usually packaged in large scale and provided for preparation workshops or manufacturers, the moisture absorption performance or the dissolution performance of the extract does not need to be concerned, the quality condition of the glabrous sarcandra herb extract can be monitored not only when the extract is prepared, but also in the feeding stage of preparation, if the moisture absorption performance or the dissolution performance changes when the preparation is fed, the quality condition can be easily solved through water conversion, or the solution method is improved. In addition, the moisture absorption and solubility of the glabrous sarcandra herb tablet cannot be directly compared with the formula granules, because the tablet is not comparable due to the addition of a large amount of auxiliary materials; the formula particles and the extractum carried by the pharmacopoeia are similar and only contain a little auxiliary materials or no auxiliary materials at all, and the formula particles and the extractum have certain technical significance compared with the two.

However, the formulation is applied directly to the clinic, directly to the patient, who receives minimal dose packaging, e.g. 1-10 g per pack, usually 1-2 g per pack, and these minimal packaged formulations are usually bagged in a composite plastic film, e.g. a commonly used packaging material cast polypropylene (CPP). These minimum packaged formulations vary in length from production to patient use, and water vapor transmission can have an effect on the hygroscopicity and solubility of the formulation. Therefore, there is a need to focus on the hygroscopicity and the effect on solubility of the formulation particles.

This test example 4 examined the hygroscopicity of some of the formulations prepared according to the invention, as follows:

and (3) testing the sample: the standard particles of example 1, the formula particles of examples 11 to 13, the formula particles of examples 21 to 23, and the formula particles of examples 31 to 33 are glabrous sarcandra herb extractum which is prepared by a method of 427 p.s.p. of the first part of China pharmacopoeia 2020 edition and has a water content of 2.86% and meets the standard;

sealing and packaging the test articles (all particles which can pass through a 60-mesh sieve) in CPP bags, wherein each bag is 2g, and placing the CPP bags in a room-temperature environment with relative humidity of 60-65% in a dark place for 30 days; for each sample, the moisture content was measured for 0 and 30 days, respectively, and their hygroscopicity was expressed as the percentage weight gain at 30 days relative to 0 days; weight% results: the weight percentages of the standard granules of example 1, the formula granules of examples 11 to 13, the formula granules of examples 31 to 32 and the glabrous sarcandra herb extract obtained by the pharmacopoeia method are all in the range of 14 to 19 percent, for example, the weight percentages of the standard granules of example 1 and the formula granules of example 11 are 17.2 percent and 15.4 percent respectively; the weight gain of the granules of the formulas of examples 21 to 23 is in the range of 2 to 4%, for example, the weight gain of the granules of the formula of example 21 is 2.73%; the example 33 formula particles all have a weight gain% in the range of 7-9%, for example the example 331 formula particles have a weight gain% of 7.86%; the weight gain results show that the moisture absorption of the formula particles of examples 21-23 is significantly lower than that of other materials, and the moisture absorption of the formula particles is significantly better than that of other materials in the aspect of avoiding moisture absorption.

This test example 4 also examined the solubility of some of the formulation granules prepared according to the invention, as follows:

referring to a device for checking the dropping pills by a 0921 disintegration time limit checking method in the four parts of the 2020 edition of Chinese pharmacopoeia, 2g of materials are added into each hanging basket, 1000ml of water is used as a solvent, 6 hanging baskets are tested for each sample, and the average time for completely dissolving each sample is calculated and used as the dissolving time T of the sample;

sealing and packaging the test articles (all particles which can pass through a 60-mesh sieve) in CPP bags, wherein each bag is 2g, and placing the CPP bags in a room-temperature environment with relative humidity of 60-65% in a dark place for 30 days; for each sample, the dissolution times T of 0 day and 30 days are measured as described above, and the percentage obtained by dividing the dissolution time T of the sample at 30 days by the dissolution time T of the sample at 0 days and multiplying by 100% is used as the percentage change in solubility, the closer the percentage is to 100%, the smaller the change in solubility properties of the product is, and the greater the percentage is than 100%, the poorer the solubility of the product is;

% change in solubility results: the dissolution time T of all samples at 0 day is in the range of 13-17 min, for example, the dissolution time T of the formula granule in example 21 is 15.2 min; the solubility change% of the standard granules of example 1, the formula granules of examples 11 to 13, the formula granules of examples 31 to 32 and the glabrous sarcandra herb extract obtained by the pharmacopoeia method are all in the range of 178 to 214%, for example, the solubility change% of the standard granules of example 1 and the solubility change% of the formula granules of example 11 are 192.2% and 203.7%, respectively; the solubility change% of the formulation particles of examples 21-23 was in the range of 107-114%, for example the solubility change% of the formulation particles of example 21 was 111.3%; the example 33 formulation particles all have a% change in solubility in the range of 135-144%, for example, the example 331 formulation particles have a% change in solubility of 141.6%; the% change in solubility results show that the degree of change in solubility of the granules of examples 21-23 is significantly lower than that of other materials, which all have significantly poor solubility after moisture absorption.

The embodiments are only for illustrating the composition and efficacy of the invention, and not for limiting the scope of the invention, therefore, it will be apparent to those skilled in the art that similar modifications can be made without departing from the structure of the invention, and all such modifications are within the scope of the invention. These should also be considered as the scope of protection of the present invention, which will not affect the effect of the implementation of the present invention and the utility of the patent.

Claims

1. A method for preparing glabrous sarcandra herb formula granules, which comprises the following steps:

(1) weighing 1 part by weight of glabrous sarcandra herb, decocting for three times, adding water with the weight 6-10 times that of the medicinal material for the first time, decocting for 0.5-2 hours, and filtering to obtain filtrate for later use; adding 5-7 times of water for the second time and the third time respectively, decocting for 0.5-2 hours each time, and filtering; mixing the three filtrates, mixing, concentrating under reduced pressure, adding sodium starch phosphate and calcium alginate into the fluid extract, and spray drying to water content below 9% to obtain powdered dry extract; the weight ratio of the added amount of the sodium starch phosphate to the solid content of the clear paste is 0.4-0.5: 100, the weight ratio of the addition amount of calcium alginate to the solid content of the filtrate is 0.2-0.3: 100, respectively;

2. The method according to claim 1, wherein the glabrous Sarcandra herb is dried whole herb of Sarcandra glabra (Thunb.) Nakai of the chloranthaceae family.

3. The method according to claim 1, wherein in the step (1), when the concentration under reduced pressure is carried out, the conditions for the concentration under reduced pressure are: the vacuum degree is-0.04 MPa to-0.08 MPa, and the temperature is 55 ℃ to 65 ℃.

4. The method according to claim 1, wherein in the step (1), the fluid extract obtained by concentrating under reduced pressure has a relative density of 1.10 to 1.15 measured at a temperature of 60 ℃.

5. The method according to claim 1, wherein in the step (1), the decoction is filtered twice by using a 200-mesh sieve.

6. The method according to claim 1, wherein in the step (1), the temperature of the inlet air of the spray dryer during the spray drying is 170 to 175 ℃.

7. The process according to claim 1, wherein the water content of the dried extract obtained by spray drying in the step (1) is less than 4%.

8. The method according to claim 1, wherein in the step (1), the dried extract in the form of powder obtained by spray drying is passed through a 80-mesh sieve.

9. The method according to claim 1, wherein in the step (2), the space between the pressing wheels is set to 0.3-0.5 mm when the dry granulation is carried out on a dry granulator.

10. The method of claim 1, further comprising the steps of:

(3) precisely weighing 500g of glabrous sarcandra herb, decocting for three times, adding 8 times of water for the first time, decocting for 1 hour, and filtering to obtain filtrate for later use; adding 6 times of water for the second time, and decocting for 1 hour; adding 6 times of water for the third time, and decocting for 1 hour; filtering, mixing the three filtrates, and mixing; and (3) concentrating under reduced pressure until the material feeding amount: the volume ratio of the concentrated solution is 1 g: 2.5ml of clear paste is frozen and dried to ensure that the water content is lower than 2 percent to obtain standard granules;

(4) measuring the content of an index substance isofraxidin in the standard granules obtained in the step (3) and the glabrous sarcandra herb formula granules obtained in the step (2), and calculating the amount of each 1g of glabrous sarcandra herb formula granules obtained in the step (2) which is equivalent to the glabrous sarcandra herb medicinal material by combining the content of the index substances in the two granules and the material feeding amount in the step (3);

11. The method according to claim 10, wherein in the step (4), the content of isofraxidin as a reference substance is determined by using the following method:

chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; using acetonitrile containing 0.1% formic acid as mobile phase A and 0.1% formic acid as mobile phase B, and performing gradient elution according to the specification in the following table; the detection wavelength is 330 nm; the number of theoretical plates is not less than 5000 according to the peak of isofraxidin and the peak of rosmarinic acid respectively;

preparation of control solutions: respectively taking a proper amount of isofraxidin and rosmarinic acid reference substances, precisely weighing, and adding 60% methanol to prepare a mixed solution containing 15 μ g of isofraxidin and 25 μ g of rosmarinic acid per 1ml, thereby obtaining the rosmarinic acid-containing mixed solution;

preparation of a test solution: taking 0.25g of test sample powder passing through a third sieve, precisely weighing, placing in a conical flask with a plug, adding 50ml of 60% methanol, weighing, carrying out ultrasonic treatment at the power of 250W and the frequency of 40kHz for 30 minutes, taking out, cooling, weighing again, complementing the weight loss by 60% methanol, shaking up, filtering, and taking out the subsequent filtrate to obtain the product;

12. The method according to claim 10, wherein in step (5), the packaged glabrous sarcandra herb formulation comprises 0.5-20 g of formulation granules in each bag.

13. A glabrous sarcandra herb granule prepared by the method of any one of claims 1 to 12.

14. Use of the glabrous sarcandra herb granules of claim 13 for the preparation of a medicament for clearing heat and removing toxicity, and relieving swelling and dissipating stagnation; or in preparing medicines for treating pneumonia, appendicitis, and cellulitis due to excessive toxic heat; or in the preparation of medicaments for the adjuvant treatment of cancer.

15. A pharmaceutical composition comprising the glabrous sarcandra herb formulation of claim 13 and optionally a pharmaceutically acceptable carrier.

16. The pharmaceutical composition of claim 15, which is in the form of a formulation for oral or injectable administration.

17. The pharmaceutical composition of claim 15, which is in the form of a tablet, capsule, granule, pill, oral liquid, or injection.