CN114028341A - Cortex moutan formula particle and preparation method thereof - Google Patents
Cortex moutan formula particle and preparation method thereof Download PDFInfo
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- CN114028341A CN114028341A CN202111362056.8A CN202111362056A CN114028341A CN 114028341 A CN114028341 A CN 114028341A CN 202111362056 A CN202111362056 A CN 202111362056A CN 114028341 A CN114028341 A CN 114028341A
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- paeonol
- moutan bark
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- 239000002245 particle Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 claims abstract description 274
- YLTGFGDODHXMFB-UHFFFAOYSA-N isoacetovanillon Natural products COC1=CC=C(C(C)=O)C=C1O YLTGFGDODHXMFB-UHFFFAOYSA-N 0.000 claims abstract description 137
- MLIBGOFSXXWRIY-UHFFFAOYSA-N paeonol Natural products COC1=CC=C(O)C(C(C)=O)=C1 MLIBGOFSXXWRIY-UHFFFAOYSA-N 0.000 claims abstract description 137
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 94
- 239000013078 crystal Substances 0.000 claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000008187 granular material Substances 0.000 claims abstract description 39
- 238000002156 mixing Methods 0.000 claims abstract description 33
- 238000001035 drying Methods 0.000 claims abstract description 23
- 239000000284 extract Substances 0.000 claims abstract description 21
- 238000001914 filtration Methods 0.000 claims abstract description 19
- 239000002671 adjuvant Substances 0.000 claims abstract description 5
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- 238000000605 extraction Methods 0.000 claims description 30
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- 239000001116 FEMA 4028 Substances 0.000 claims description 29
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical group OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 29
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 29
- 229960004853 betadex Drugs 0.000 claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 19
- 238000001256 steam distillation Methods 0.000 claims description 18
- 238000003809 water extraction Methods 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 10
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- 238000004519 manufacturing process Methods 0.000 claims description 5
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- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
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- 239000003814 drug Substances 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000001694 spray drying Methods 0.000 description 11
- 238000009835 boiling Methods 0.000 description 8
- 238000000227 grinding Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000084 colloidal system Substances 0.000 description 6
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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- 239000004375 Dextrin Substances 0.000 description 3
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- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 3
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- 240000005001 Paeonia suffruticosa Species 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
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- 238000009210 therapy by ultrasound Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 description 1
- YMGFTDKNIWPMGF-UCPJVGPRSA-N Salvianolic acid A Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C(=C(O)C(O)=CC=1)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-UCPJVGPRSA-N 0.000 description 1
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- 229930183842 salvianolic acid Natural products 0.000 description 1
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- 229940126680 traditional chinese medicines Drugs 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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Abstract
The invention provides a moutan bark formula particle and a preparation method thereof, and the preparation method of the moutan bark formula particle comprises the following steps: distilling cortex moutan decoction pieces with straight-through steam, collecting volatile condensate A, extracting the cortex moutan decoction pieces with water to obtain water extractive solution and volatile condensate B, mixing volatile condensates A, B, and standing to obtain paeonol crystal; clathrating paeonol crystal with adjuvant to obtain clathrate; filtering the water extract, concentrating to obtain concentrated solution, mixing with the clathrate, drying, and granulating to obtain cortex moutan granule; the mass ratio of the moutan bark decoction pieces to the paeonol crystal used in the inclusion process is 100 (1.0-2.0). According to the invention, the amount of paeonol crystals added in the prepared moutan bark formula particle is limited, so that the content of paeonol in the prepared formula particle is ensured to be in the range of traditional decoction, the difference among batches is reduced to the maximum extent, and the drug effect of the moutan bark formula particle is consistent with that of the traditional decoction.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicine formula granules, in particular to cortex moutan formula granules and a preparation method thereof.
Background
The traditional Chinese medicine formula granules are series products which are prepared by taking traditional Chinese medicine decoction pieces which accord with pharmacopoeia and processing specifications as raw materials according to the physicochemical properties of the effective components of the traditional Chinese medicine and carrying out the steps of proper extraction, concentration, drying, granulation and the like. The traditional Chinese medicine formula granule improves the stability of the traditional Chinese medicine preparation, is a complementary form of traditional Chinese medicine decoction pieces used in traditional Chinese medicine clinical practice, and has the advantages of accurate dosage, convenient preparation, convenient taking, safety, sanitation and the like.
At present, the preparation process of most traditional Chinese medicine formula granules is more sufficient in extraction of effective components and higher in utilization rate of medicinal materials compared with the traditional decoction. However, for some traditional Chinese medicines containing volatile components, the volatile components are easy to lose during extraction or granulation by the conventional process, and if the lost volatile components are effective components, the drug effect is affected, so that the drug effects of the granules and the decoction are inconsistent. For example, in the moutan bark dispensing granule, the volatile component of paeonol is an effective component, and because the component is very easy to volatilize by heating, especially in the concentrating and drying stages, the component cannot be stably stored, so that the paeonol is seriously volatilized, and the requirement of the drug effect cannot be met after drying. In order to prevent the loss of effective components, the prior art firstly extracts the volatile components in the tree peony bark and then adds the volatile components in the tree peony bark in the granulation process, thereby ensuring the drug effect.
For example: a method for preparing cortex moutan formula granule is disclosed in Chinese Herbal medicine Chinese Traditional medicinal and Herbal Drugs Vol.46, No. 24, which comprises distilling cortex moutan decoction pieces by steam distillation, refrigerating collected distillate overnight, precipitating white crystal (paeonol), filtering, dissolving white crystal with appropriate amount of ethanol, slowly dripping 7 times of beta-cyclodextrin solution (dissolving beta-cyclodextrin with 20 times of water in 50-60 deg.C water bath, standing at room temperature), stirring for 30min, refrigerating with refrigerator, standing overnight, drying below 45 deg.C to obtain clathrate, and keeping; and extracting the residues after distillation to obtain a water decoction, concentrating, vacuum drying, adding the inclusion compound, and mixing to obtain the cortex moutan formula granules.
That is, the method disclosed in the above document is to mix the dry powder of the inclusion compound with the dry powder of the water decoction and granulate, and the loss of paeonol caused by the concentration and drying steps is effectively avoided by the way of supplementing paeonol in the granulating process, thereby satisfying the content requirement of the active ingredients. However, the particle sizes of the inclusion compound and the dry powder of the decoction are different, so that the mixture is not uniform enough, and the uniformity of the quality of the formula particles is difficult to ensure; in addition, the process is to completely add the extracted paeonol inclusion compound into the dry powder of the water decoction, and because the total amount of the paeonol extracted from each batch is different, the content of the paeonol in the dry powder of the inclusion compound in some batches can not meet the requirement of the traditional decoction, and the content of the paeonol in some batches can exceed the requirement of the traditional decoction, so that the content of the effective components in the granules in each batch is uneven, the drug effect is unequal, and the drug effect of the granules is difficult to ensure to be equal to that of the traditional decoction.
Chinese patent document CN101491546A discloses a preparation method of a Chinese medicinal formula granule containing volatile oil effective components, which specifically comprises selecting medicinal materials with volatile oil as effective components, removing impurities, crushing or chopping; soaking the cleaned and crushed materials in water, extracting volatile oil by direct steam method, and quantitatively collecting volatile oil; adding water into the materials after the volatile oil is extracted, heating and refluxing for extraction; vacuum concentrating the extractive solution under reduced pressure to obtain concentrated solution; adding beta-cyclodextrin and purified water into the volatile oil, and performing inclusion on the volatile oil by using a colloid mill grinding method to obtain a volatile oil beta-cyclodextrin inclusion compound; mixing the volatile oil beta-cyclodextrin inclusion compound with the extract concentrated solution uniformly, preheating, and spray drying to obtain spray dried powder; mixing the spray dried powder with dextrin or lactose adjuvant to obtain total mixed powder; and (4) granulating the total mixed powder by a dry method, and finishing granules to obtain the traditional Chinese medicine formula granules.
In the method disclosed in the above document, the concentrated solution is mixed with the inclusion compound, and then drying and granulating are carried out, which ensures the uniformity of mixing and the uniformity of granule quality; however, the effective components of the volatile oil in the traditional Chinese medicine formula granule disclosed in the document are not identical to the effective components of the volatile oil in the traditional decoction in composition and content, so that the medicine effect is inconsistent with the traditional decoction, and the stability of the quality of the formula granule is difficult to ensure.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the defects that the moutan bark formula particle in the prior art has different effects with the traditional decoction and the stability of the moutan bark formula particle among batches is poor, thereby providing the preparation method of the moutan bark formula particle with the same effect with the traditional decoction and stable quality.
Therefore, the invention provides the following technical scheme:
a preparation method of cortex moutan radicis formula granules comprises the following steps:
distilling cortex moutan decoction pieces with straight-through steam, collecting volatile condensate A, extracting the cortex moutan decoction pieces with water to obtain water extractive solution and volatile condensate B, mixing volatile condensates A, B, and standing to obtain paeonol crystal;
clathrating paeonol crystal with adjuvant to obtain clathrate;
filtering the water extract, concentrating to obtain concentrated solution, mixing with the clathrate, drying, and granulating to obtain cortex moutan granule;
wherein the mass ratio of the moutan bark decoction pieces to the paeonol crystals used in the inclusion process is 100 (1.0-2.0).
Furthermore, the auxiliary material is beta-cyclodextrin, and the mass ratio of the paeonol crystal to the beta-cyclodextrin in the inclusion process is 1 (7-9).
Further, when water is added for extraction,
carrying out water extraction for the first time: firstly, mixing the distilled moutan bark decoction pieces with water for one time, and carrying out water extraction to obtain a water extract 1 and volatile condensate B1 collected in the water extraction process;
and (3) water extraction for the second time: mixing the cortex moutan decoction pieces subjected to primary water extraction with water for the second time, and performing water extraction to obtain water extract 2 and volatile condensate B2 collected in the water extraction process;
and combining the water extract 1 and the water extract 2 to obtain the water extract, and combining the volatile condensate B1 and the volatile condensate B2 to obtain the volatile condensate B.
Further, steam distillation is carried out by crushing cortex moutan decoction pieces, soaking in water, and steam distillation for 20-120 min. Preferably, the straight-through steam distillation is 60 min.
Furthermore, when the moutan bark decoction pieces are soaked in water thoroughly, the mass ratio of the moutan bark decoction pieces to the water is 1 (0.5-1.5).
Wetting out means that the drug is wetted with water in stages until the drug is free of filling (i.e., soaked).
Further, when water is added for extraction, the mass ratio of the moutan bark decoction pieces to the water is 1 (6-12); preferably, the mass ratio of the moutan bark decoction pieces to the water in the water extraction is 1: 10.
The time of the first water extraction is 0.5-1.5 h; the time of the second water extraction is 0.5-1 h.
Further, the density of the concentrated solution is 1.05-1.10g/cm3(60℃)。
Further, during inclusion, firstly, dissolving paeonol crystals in ethanol, and then mixing and grinding the paeonol crystals, beta-cyclodextrin and water for 20-60 min; preferably, the ethanol solution of paeonol crystal is mixed with beta-cyclodextrin and water and ground for 60 min.
Further, the mass ratio of the paeonol crystal to the ethanol is 1 (4-8); preferably, the mass ratio of the paeonol crystal to the ethanol is 1: 8;
the mass ratio of the beta-cyclodextrin to the water is 1 (2-4); preferably, the mass ratio of beta-cyclodextrin to water is 1: 3.
The ethanol is 95% ethanol by volume fraction.
Further, the standing temperature is 3-8 ℃ when paeonol crystals are separated out by standing.
Further, the method also comprises the steps of mixing and drying the concentrated solution and the inclusion compound, mixing with auxiliary materials and granulating;
wherein the addition amount of the auxiliary materials is not more than 11 percent of the mass of the moutan bark decoction pieces.
When the dry powder is prepared by drying, spray drying or other drying methods (such as drying under normal pressure, drying under reduced pressure, freeze drying, etc.) can be adopted.
Wherein the parameters of spray drying are as follows: preheating temperature of mixture of clathrate and concentrated solution: 50-60 ℃; air inlet temperature of the spray tower: 155-165 ℃; air outlet temperature of the spray tower: 65-75 ℃; atomizer frequency of the spray tower: 260-270 Hz; frequency of a feeding pump of the spray tower: 30-45Hz (based on the mobile phase of the spray powder).
The invention also provides the moutan bark formula particle prepared by the preparation method of the moutan bark formula particle.
The technical scheme of the invention has the following advantages:
1. the inventor finds that the reason why the drug effect of the existing granules containing volatile oil is inconsistent with the drug effect of the traditional decoction is as follows: the granule added with volatile oil has inconsistent components and contents of volatile oil. Specifically, in the existing granule containing volatile oil, the collected volatile oil is completely returned to the water extract in the preparation process, and because the raw material batches are different, the amount of the collected volatile oil is different, and the loss amount of the volatile oil is also different in the concentration and drying processes, the final finished product has a certain deviation from the traditional decoction, and the content of the volatile oil in the standard decoction may not meet the content requirement of the volatile oil in the standard decoction or obviously exceeds the content of the volatile oil in the standard decoction. Meanwhile, due to different obtaining modes of the volatile oil, the composition components of the volatile oil are inconsistent, and the situation can cause the obvious difference between the final finished product of the formula granule and the traditional decoction in terms of components. In addition, the conventional measurement method for measuring the content of volatile components in the traditional decoction is to measure the amount of volatile oil by adopting the traditional extraction method, and the content of the volatile oil obtained by the measurement is inaccurate. In conclusion, the drug effect of the existing granules containing volatile oil components is inconsistent with the drug effect of the traditional decoction.
In the preparation method of the moutan bark formula particle provided by the invention, after the volatile condensate A is extracted by direct steam distillation, adding water, reflux-extracting to obtain extractive solution, collecting volatile condensate B volatilized during water extraction, can reduce the loss of paeonol in the extraction process, improve the extraction amount of the paeonol, avoid the problem that the amount of the paeonol obtained by extraction is insufficient and can not reach the volatile oil content in the standard decoction, ensure that the invention can obtain enough or even excessive paeonol crystals, and then, the paeonol crystal is conveniently added into the water extract in a limited amount, and particularly, the mass ratio of the moutan bark decoction pieces to the paeonol crystal used in the inclusion process is limited to 100: (1.0-2.0), thereby ensuring that the paeonol crystal (added in a limited amount) extracted from the fixed amount of cortex moutan decoction pieces and the drug effect of the formula granule prepared from the concentrated solution are highly consistent with that of the traditional decoction.
The reason why the above-mentioned limited addition amount can be kept highly consistent with the conventional decoction is that: firstly, the content of volatile components (crystals) in the traditional decoction is measured by adopting the high performance liquid chromatography, the amount of the volatile oil is not measured by adopting the traditional volatile component (volatile oil) extraction method, and the amount of the paeonol crystals obtained by the measuring method in the invention is more accurate compared with the common volatile oil measuring method. Secondly, the volatile oil in the invention is mainly paeonol crystals, and the essential consistency of the content of the paeonol crystals and the content of the active ingredients of the standard decoction can be effectively ensured as long as the content of the paeonol crystals is ensured to be consistent with the content of the standard decoction; the purity of the paeonol in the volatile condensate A and the volatile condensate B obtained in the invention is extremely high, which can reach more than 97%, and paeonol crystals can be obtained after standing; therefore, the method only needs to control the content of the paeonol crystals in the returned extracting solution to be basically consistent with the content of the paeonol crystals in the standard decoction. Finally, the method strictly prepares 21 batches of traditional decoction according to the management standard of decoction rooms of medical institutions, and determines the content range of paeonol in the traditional decoction by combining high performance liquid chromatography to determine the content of paeonol in the traditional decoction, and limits the range of adding paeonol crystals into the prepared moutan bark formula particles according to the content range, so that the mass ratio of the moutan bark decoction pieces to the paeonol crystals used in the inclusion process is 100 (1.0-2.0), the content of the paeonol in the prepared formula particles is effectively ensured to be in the range of the traditional decoction, the difference between batches is reduced to the maximum extent, and the problems that the content of the paeonol in the moutan bark formula particles is not equal to the content of the paeonol in the traditional decoction and the drug effect is not consistent due to no reference of the adding amount are solved; therefore, the paeonol content of the prepared moutan bark formula particle is highly consistent with that of the traditional decoction, and the quality of the moutan bark formula particle is uniform among different batches.
2. The inventor verifies that the non-included paeonol can cause great loss under the condition that the temperature is higher than 50 ℃, so that the content of the paeonol in batches is unstable, and the drug effect is unstable; the optimization of the inclusion process of the paeonol crystal and the auxiliary materials can better and effectively protect the paeonol crystal, avoid influencing the content of the paeonol in the subsequent drying process, ensure that the medicinal effects of the formula particles in different batches are basically consistent, and have better stability.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
Example 1
The embodiment provides a preparation method of a moutan bark formula particle, which comprises the following steps:
weighing 4kg of cortex moutan decoction pieces, crushing to a particle size of 19mm, adding 4kg of water, soaking thoroughly, distilling for 1h by straight-through steam distillation, and collecting volatile condensate A;
adding water into the material extracted by the straight-through steam distillation method for extraction twice: boiling and extracting cortex moutan decoction pieces with water at a mass ratio of 1:8 for 1h, collecting volatile condensate B1, and pouring out extractive solution 1; adding cortex moutan decoction pieces with 6 times of water, boiling and extracting for 1 hr, collecting volatile condensate B2, and pouring out extractive solution 2;
mixing the above extractive solutions 1 and 2, filtering with 150 mesh filter cloth, and concentrating under reduced pressure to obtain concentrated solution with density of 1.05(60 deg.C);
mixing the volatile condensate A, B1 and B2, standing at 5 deg.C for 24 hr, filtering the precipitated paeonol crystal, and drying at 40 deg.C;
weighing 60g of the paeonol crystals, and adding 480g of ethanol for dissolving; weighing 480g of beta-cyclodextrin, and dissolving in 1440g of water; pouring the ethanol solution of paeonol and the water solution of beta-cyclodextrin into a colloid mill, and grinding for 20min to obtain an inclusion compound;
mixing the clathrate with the concentrated solution, and spray drying to obtain dry powder; the parameters of the spray drying were: preheating temperature of mixture of clathrate and concentrated solution: 60 ℃; air inlet temperature of the spray tower: 160 ℃; air outlet temperature of the spray tower: 65 ℃; atomizer frequency of the spray tower: 260 Hz; frequency of a feeding pump of the spray tower: 40Hz
(based on spraying powder mobile phase);
and (4) granulating the dried powder to obtain the moutan bark formula granules.
Example 2
The embodiment provides a preparation method of a moutan bark formula particle, which comprises the following steps:
weighing 8kg of cortex moutan decoction pieces, crushing to 19mm, adding 4kg of water, soaking thoroughly, distilling for 20min by straight-through steam distillation, and collecting volatile condensate A;
adding water into the material extracted by the straight-through steam distillation method for extraction twice: boiling and extracting cortex moutan decoction pieces with water at a mass ratio of 1:12 for 0.5 hr, collecting volatile condensate B1, and pouring out extractive solution 1; adding 10 times of water into cortex moutan decoction pieces, boiling and extracting for 0.5h, collecting volatile condensate B2, and pouring out extractive solution 2;
mixing the above extractive solutions 1 and 2, filtering with 150 mesh filter cloth, and concentrating under reduced pressure to obtain concentrated solution with density of 1.10(60 deg.C);
mixing the volatile condensate A, B1 and B2, standing at 3 deg.C for 24 hr, filtering the precipitated paeonol crystal, and drying at 40 deg.C;
weighing 40g of the paeonol crystals, and adding 240g of ethanol for dissolving; weighing 360g of beta-cyclodextrin, and dissolving in 1080g of water; pouring the ethanol solution of paeonol and the water solution of beta-cyclodextrin into a colloid mill, and grinding for 40min to obtain an inclusion compound;
mixing the clathrate with the concentrated solution, and spray drying to obtain dry powder; the parameters of the spray drying were: preheating temperature of mixture of clathrate and concentrated solution: 50 ℃; air inlet temperature of the spray tower: 155 ℃; air outlet temperature of the spray tower: 70 ℃; atomizer frequency of the spray tower: 265 Hz; frequency of a feeding pump of the spray tower: 30Hz (based on the mobile phase of the spraying powder);
mixing the dried powder with 440g of dextrin, and granulating to obtain the cortex moutan formula granule.
Example 3
The embodiment provides a preparation method of a moutan bark formula particle, which comprises the following steps:
weighing 8kg of cortex moutan decoction pieces, crushing to a particle size of 19mm, adding 12kg of water, soaking thoroughly, distilling for 2h by straight-through steam distillation, and collecting volatile condensate A;
adding water into the material extracted by the straight-through steam distillation method for extraction twice: boiling and extracting cortex moutan decoction pieces with water at a mass ratio of 1:6 for 1.5h, collecting volatile condensate B1, and pouring out extractive solution 1; adding 6 times of water amount of cortex moutan decoction pieces, boiling and extracting for 1 hr, collecting volatile condensate B2, and pouring out extractive solution 2;
mixing the above extractive solutions 1 and 2, filtering with 150 mesh filter cloth, and concentrating under reduced pressure to obtain concentrated solution with density of 1.07(60 deg.C);
mixing the volatile condensate A, B1 and B2, standing at 8 deg.C for 24 hr, filtering the precipitated salvianolic acid crystal, and drying at 40 deg.C;
weighing 80g of the paeonol crystals, and adding 320g of ethanol for dissolving; weighing 560g of beta-cyclodextrin, and dissolving in 1440g of water; pouring the ethanol solution of paeonol and the water solution of beta-cyclodextrin into a colloid mill, and grinding for 60min to obtain an inclusion compound;
mixing the clathrate with the concentrated solution, and spray drying to obtain dry powder; the parameters of the spray drying were: preheating temperature of mixture of clathrate and concentrated solution: 55 ℃; air inlet temperature of the spray tower: 165 ℃; air outlet temperature of the spray tower: 75 ℃; atomizer frequency of the spray tower: 270 Hz; frequency of a feeding pump of the spray tower: 45Hz (based on the mobile phase of the spraying powder);
mixing the dried powder with 240g of dextrin, and granulating to obtain the moutan bark formula granules.
Comparative example 1
The comparative example provides a preparation method of a moutan bark formula particle, which comprises the following steps:
weighing 4kg of cortex moutan decoction pieces, crushing to a particle size of 19mm, adding 4kg of water, soaking thoroughly, distilling for 1h by straight-through steam distillation, and collecting volatile condensate A;
adding water into the material extracted by the straight-through steam distillation method for extraction twice: boiling and extracting paeonol decoction pieces and water at a mass ratio of 1:8 for 1h during the first extraction, collecting volatile condensate B1, and pouring out extract 1; adding 6 times of water into paeonol decoction pieces, boiling and extracting for 1 hr, collecting volatile condensate B2, and pouring out extractive solution 2;
mixing the above extractive solutions 1 and 2, filtering with 150 mesh filter cloth, and concentrating under reduced pressure to obtain concentrated solution with density of 1.05(60 deg.C);
mixing the volatile condensate A, B1 and B2, standing at 5 deg.C for 24 hr, filtering the precipitated paeonol crystal, and drying at 40 deg.C;
weighing 30g of the paeonol crystals, and adding 240g of ethanol for dissolving; weighing 480g of beta-cyclodextrin, and dissolving in 1440g of water; pouring the ethanol solution of paeonol and the water solution of beta-cyclodextrin into a colloid mill, and grinding for 20min to obtain an inclusion compound;
mixing the clathrate with the concentrated solution, and spray drying to obtain dry powder; the parameters of the spray drying were: preheating temperature of mixture of clathrate and concentrated solution: 60 ℃; air inlet temperature of the spray tower: 160 ℃; air outlet temperature of the spray tower: 65 ℃; atomizer frequency of the spray tower: 260 Hz; frequency of a feeding pump of the spray tower: 40Hz (based on the mobile phase of the spraying powder);
and (4) granulating the dried powder to obtain the moutan bark formula granules.
Experimental example 1 determination of Paeonol content in conventional decoction
Randomly purchasing 21 batches of cortex moutan decoction pieces in the market, preparing a traditional decoction according to the management standard of decoction rooms of medical institutions, namely soaking for 30min, decocting twice, adding water 8 times the amount of the decoction pieces in the first decoction, decocting for 20min, adding water 6 times the amount of the decoction pieces in the second decoction, decocting for 15min, filtering, combining the filtrates of the two decoctions, weighing, and determining the content of paeonol in the traditional decoction according to a high performance liquid chromatography (0512 in the four ministry of communications in 2015 edition of Chinese pharmacopoeia), wherein the specific method comprises the following steps:
chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; methanol-water (45: 55) is used as a mobile phase; the detection wavelength was 274 nm. The number of theoretical plates is not less than 5000 calculated according to the peak of paeonol.
Preparation of control solutions: taking a proper amount of paeonol (batch number: 110708-201407, China institute for food and drug testing) reference substances, precisely weighing, and adding methanol to prepare a solution containing 20 mu g of paeonol per 1 mL.
Preparation of a test solution: taking 1mL of the traditional decoction, placing in a 50mL volumetric flask, adding water to a constant volume to a scale, shaking up, filtering, and taking a subsequent filtrate to obtain the final product.
The determination method comprises the following steps: precisely sucking 2 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring. The test results are shown in table 1 below.
TABLE 1 test results
As can be seen from the data in the above table, the average value of the paeonol content in 21 batches of traditional decoctions is 28.6mg/g, and the content allowable range is as follows: 22.0-34.0 mg/g. Therefore, the adding amount of the paeonol crystals in the moutan bark formula particles is guided by the method.
Experimental example 2
The paeonol content of the moutan bark formula particles prepared in the embodiments and the comparative examples is measured by high performance liquid chromatography (the four-part general rule 0512 of the 2015 version in the pharmacopoeia of China):
chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; methanol-water (45: 55) is used as a mobile phase; the detection wavelength was 274nm, and the flow rate was 0.4 mL/min. The number of theoretical plates is not less than 5000 calculated according to the peak of paeonol.
Preparation of control solutions: taking a proper amount of paeonol (batch No. 110708-.
Preparation of a test solution: precisely weighing 0.1g of cortex moutan formula granules prepared in each example and comparative example, respectively placing into conical flasks with plugs, precisely adding 20mL of methanol, sealing the plugs, weighing, performing ultrasonic treatment for 20min, taking out, placing at room temperature, weighing again, supplementing the lost weight with methanol, shaking up, filtering, and taking the subsequent filtrate.
The determination method comprises precisely sucking 2 μ l of each of the reference solution and the sample solution, and injecting into high performance liquid chromatograph for determination. The specific test results are shown in table 2 below.
TABLE 2 test results
The data in the above table show that the content of paeonol in the moutan bark formula particle prepared by the preparation method of the moutan bark formula particle provided by the invention is within the range of the content of paeonol in the traditional decoction (22.0-34.0mg/g), which indicates that the effect of the moutan bark formula particle is consistent with that of the traditional decoction.
Experimental example 3 investigation of concentration Process
In the experimental example, the concentration process for preparing the moutan bark formula particles is considered, the concentration temperature of the traditional decoction is controlled below 50 ℃ (the melting point of paeonol is 50 ℃) because the concentration temperature has large influence on the extraction of effective components, but in the actual production process, in order to improve the production efficiency and reduce the energy consumption, the concentration temperature needs to be considered, and the concentration temperature with high efficiency is determined on the premise of not influencing the quality.
Procedure of experiment
Taking 200g of cortex moutan decoction pieces, decocting according to a traditional decoction (in the management standard of decoction rooms of medical institutions), soaking for 30 minutes, decocting twice, adding water with the mass 8 times of that of the decoction pieces in the first decoction, decocting for 20 minutes, adding water with the mass 6 times of that of the decoction pieces in the second decoction, decocting for 15 minutes, respectively filtering by 150-mesh filter cloth, combining filtrates, cooling, weighing, shaking uniformly, averagely dividing into 4 parts, wherein each part is about 777.9g, respectively carrying out rotary evaporation and concentration by using water baths with the temperature of 60 ℃, 70 ℃, 80 ℃ and 90 ℃, and concentrating until the ratio of the materials to the liquid is about 1:1, diluting 10mL of the solution to 77.8g (consistent with the standard decoction concentration) by adding water, and measuring by using a characteristic spectrum measuring method, wherein the specific test results are shown in the following table.
The characteristic spectrum determination method comprises the following steps:
chromatographic conditions and system applicability test a chromatographic column using octadecylsilane chemically bonded silica as a filler (column length 100mm, inner diameter 2.1mm, particle size 1.7 μm); acetonitrile is taken as a mobile phase A, 0.1 percent formic acid is taken as a mobile phase B, and elution is carried out according to the following gradient; the detection wavelength is 254nm, the column temperature is 35 ℃, and the flow rate is 0.6 mL/min.
Preparation of reference substance solution Paeonol reference substance is precisely weighed, and methanol is added to prepare solution containing 20 μ g Paeonol per 1 mL.
TABLE 3 Peak area of characteristic peaks at different concentration temperatures
From the results in the above table, it can be seen that, in the sample with the same concentration, the peak area of peak 14 (paeonol) in the traditional decoction stock solution is 4367142, the peak area of paeonol is 224950 under the concentration at 60 ℃, the peak area is reduced by 94.8%, the peak area is reduced by 99.2% after the concentration at 90 ℃, the paeonol is definitely completely lost when the moutan bark extract is concentrated at the temperature of 70-90 ℃ in the actual large-scale production process, and other characteristic peaks are basically unchanged. Based on the above, the invention provides that the temperature is not controlled in the concentration process, and the content of the paeonol in the finished product particles is ensured by adopting a method of quantitatively adding the paeonol, so that the paeonol is equivalent to the traditional decoction.
Experimental example 4 study of inclusion Process
Study of inclusion parameters
As shown in the following tables 4-5, the ratio (A) of paeonol crystals to beta-cyclodextrin, the ratio (B) of beta-cyclodextrin to water and the inclusion time (C) are selected as investigation factors, 3 levels are respectively taken to carry out an L9(34) orthogonal experiment, the yield and the inclusion rate are taken as investigation indexes, and the optimal inclusion parameters are screened, and the results are shown in the following tables 6-7.
TABLE 4 investigation of factors
| Factors of the fact | A | B | C/min |
| 1 | 1：7 | 1：2 | 20 |
| 2 | 1：8 | 1：3 | 40 |
| 3 | 1：9 | 1：4 | 60 |
TABLE 5 factor level table
Determination of the investigation index: the inclusion rate is an important index for examining the degree of inclusion of a drug, and the yield of the inclusion compound reflects the actual yield, so the inclusion rate and the yield are selected as the examination indexes.
Inclusion rate (%) - (amount of paeonol in the clathrate/amount of paeonol added × 100%;
the yield (%). is the clathrate mass/(paeonol crystal mass + beta-cyclodextrin mass) × 100%;
the inclusion method comprises the following steps: weighing paeonol, adding about 8 times of ethanol to dissolve, weighing a certain amount of beta-cyclodextrin, adding water in proportion to obtain saturated solution, pouring the above solutions into a colloid mill, grinding according to orthogonal experiment time, taking out and placing in a beaker after grinding, placing in a refrigerator for cold storage for 24h, filtering, drying the inclusion compound at 40 ℃ to obtain the inclusion compound, and weighing.
The determination yield is as follows: accurately weighing 0.1g of inclusion compound, placing the inclusion compound in a 10mL volumetric flask, adding 95% ethanol by volume content to the scale, performing ultrasonic treatment for 20min, cooling to room temperature, performing constant volume treatment with ethanol, filtering, taking 2 μ l of subsequent filtrate, injecting into a high performance liquid chromatograph, measuring the paeonol content according to the high performance liquid chromatography (0512 in the four-part general regulation of the 2015 edition of Chinese pharmacopoeia), and calculating the inclusion rate.
TABLE 6 Paeonol inclusion orthogonal experiment results
The orthogonal experiment results in the table above were analyzed by using Design Expert 10 software, and the results are as follows by software fusion with yield and inclusion rate as evaluation indexes:
TABLE 7 results of orthogonal experiments of paeonol inclusion processed by software
| Numbering | A | B | C | Yield% | Inclusion rate% | Composite index scoring |
| 1 | 1:9 | 1:3 | 60 | 83.066 | 96.133 | 0.976 |
| 2 | 1:9 | 1:3 | 20 | 81.716 | 97.920 | 0.920 |
| 3 | 1:9 | 1:4 | 60 | 79.639 | 94.160 | 0.785 |
| 4 | 1:9 | 1:3 | 40 | 80.742 | 90.177 | 0.775 |
| 5 | 1:9 | 1:4 | 20 | 78.289 | 95.947 | 0.736 |
| 6 | 1:9 | 1:2 | 60 | 78.499 | 91.367 | 0.687 |
| 7 | 1:7 | 1:3 | 60 | 82.372 | 81.903 | 0.677 |
| 8 | 1:7 | 1:3 | 20 | 81.022 | 83.690 | 0.669 |
| 9 | 1:9 | 1:2 | 20 | 77.149 | 93.153 | 0.634 |
| 10 | 1:9 | 1:4 | 40 | 77.316 | 88.203 | 0.580 |
From the data in the above table, when the paeonol crystal: beta-cyclodextrin: 1 part of water: 9: when the inclusion time is 60min, the yield and the inclusion rate are closest to the target values (the probability is 0.976), and therefore, the optimal process conditions for determining the inclusion are as follows: paeonol crystal: beta-cyclodextrin: 1 part of water: 9: 27, the inclusion time is 60 min.
Experimental example 5 determination of the amount of paeonol crystals added
The amount of paeonol crystals to be added in the preparation of the moutan bark particles is calculated according to the paeonol content in the traditional decoction of 21 batches of moutan bark in experimental example 3, the yield in experimental example 4, the paeonol content in paeonol crystals (considering that the mass production cannot reach the fine laboratory experiment and the content is relatively reduced), and the inclusion rate.
The amount of paeonol crystal added (paeonol content in the traditional decoction of cortex moutan in experimental example 3 x yield in experimental example 4)/(paeonol content in paeonol crystal in experimental example 4 x inclusion rate in experimental example 4 x 100) x 100%;
the calculation shows that paeonol crystals with the mass of 1.0-2.0% of that of the moutan bark decoction pieces used for extraction are added when the moutan bark particles are prepared, and the limit range of the content determination of the paeonol in the traditional decoction of the moutan bark can be met.
Experimental example 6 study of extraction Process
The first process comprises the following steps: the method comprises the steps of taking 4000g of moutan bark decoction pieces, adding 10 times of water by mass, soaking for 30min, extracting twice for 1h each time, collecting volatile oil respectively, after extraction is finished, placing the volatile oil collected twice in a refrigeration house respectively, freezing to separate out paeonol crystals, filtering the paeonol crystals, drying at 40 ℃ for 8h, and weighing the paeonol crystals, wherein the results are shown in the following table 8.
TABLE 8 Process one extraction results
As can be seen from the data in the above table, if the collection of paeonol is performed only during the extraction of moutan bark, the amount of paeonol obtained is not sufficient for use in packaging (calculated from the paeonol content of the conventional decoction), and therefore, the above extraction process needs to be optimized.
And a second process: 4000g of moutan bark decoction pieces are taken, 4000g of water is added, after thorough moistening, no water is added, the straight-through steam distillation method is adopted to directly steam for 1h to collect volatile oil, then water with the mass being 10 times that of the volatile oil is added for twice, each time of extraction is carried out for 1h, the volatile oil is continuously and respectively collected while an extracting solution is obtained, after the extraction is finished, the volatile oil collected for three times is placed in a refrigeration house to separate out paeonol crystals, the paeonol crystals are filtered and dried at 40 ℃ for 8h, and then the weight of the paeonol crystals is weighed, and the results are shown in the following table 9.
TABLE 9 Process two extraction results
As can be seen from the data in the above table, if the collection of paeonol is performed only at the time of straight-through steam distillation, the amount of the obtained paeonol is insufficient for the packaging (calculated from the paeonol content of the conventional decoction), but if the paeonol collected at the time of obtaining the extract is combined, the amount of the paeonol may be sufficient for the packaging (calculated from the paeonol content of the conventional decoction).
The data in table 8 and table 9 above show that the extraction process of the present invention is performed by directly-passing steam distillation to collect most of the paeonol, adding water to extract the paeonol twice, and collecting the paeonol at the same time, so as to prevent the loss caused by volatilization of the paeonol during liquid extraction, improve the extraction efficiency of the paeonol, extract enough paeonol crystals from a fixed amount of moutan bark decoction pieces, and add the paeonol crystals in a limited amount, thereby ensuring that the content of the paeonol in the medicinal effect of the formula granules prepared from the paeonol crystals (added in a limited amount) extracted from the fixed amount of moutan bark decoction pieces is consistent with that of the traditional decoction.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the spirit or scope of the invention.
Claims (10)
1. The preparation method of the moutan bark formula particle is characterized by comprising the following steps:
distilling cortex moutan decoction pieces with straight-through steam, collecting volatile condensate A, extracting the cortex moutan decoction pieces with water to obtain water extractive solution and volatile condensate B, mixing volatile condensates A, B, and standing to obtain paeonol crystal;
clathrating paeonol crystal with adjuvant to obtain clathrate;
filtering the water extract, concentrating to obtain concentrated solution, mixing with the clathrate, drying, and granulating to obtain cortex moutan granule;
wherein the mass ratio of the moutan bark decoction pieces to the paeonol crystals used in the inclusion process is 100 (1.0-2.0).
2. The method for preparing the moutan bark dispensing granule as claimed in claim 1, wherein the excipient is β -cyclodextrin, and the mass ratio of the paeonol crystal to the β -cyclodextrin used in the inclusion process is 1 (7-9).
3. The method for preparing moutan bark formulation granule according to claim 1 or 2, wherein, when extracting with water,
firstly, mixing the distilled moutan bark decoction pieces with water for one time, and carrying out water extraction to obtain a water extract 1 and volatile condensate B1 collected in the water extraction process;
mixing the cortex moutan decoction pieces subjected to primary water extraction with water for the second time, and performing water extraction to obtain water extract 2 and volatile condensate B2 collected in the water extraction process;
and combining the water extract 1 and the water extract 2 to obtain the water extract, and combining the volatile condensate B1 and the volatile condensate B2 to obtain the volatile condensate B.
4. The method for preparing the moutan bark dispensing granule according to any one of claims 1 to 3, wherein the straight steam distillation is performed by crushing the moutan bark decoction pieces, soaking in water to moisten them thoroughly, and then straight steam distillation for 20-120 min.
5. The method for preparing the moutan bark decoction pieces according to claim 4, wherein the mass ratio of the moutan bark decoction pieces to the water is 1 (0.5-1.5) when the moutan bark decoction pieces are soaked and moistened with the water.
6. The method for preparing the moutan bark decoction pieces according to any one of claims 1 to 5, wherein the mass ratio of the moutan bark decoction pieces to water is 1 (6-12) when water is added for extraction.
7. The method of preparing the moutan bark formulation particle of any one of claims 1 to 6, wherein the concentration has a density of 1.05 to 1.10g/cm3。
8. The method for preparing the moutan bark granule according to any one of claims 2 to 7, wherein the paeonol crystal is first dissolved in ethanol and then mixed with β -cyclodextrin and water and ground for 20 to 60 min;
the mass ratio of the beta-cyclodextrin to the water is 1 (2-4);
the mass ratio of the paeonol crystal to the ethanol is 1 (4-8).
9. The method for preparing the moutan bark dispensing granule according to any one of claims 1 to 8, further comprising the steps of mixing the concentrated solution and the inclusion compound, drying, mixing with an adjuvant, and granulating;
wherein the adding amount of the auxiliary materials is not more than 11 wt% of the mass of the moutan bark decoction pieces.
10. The moutan bark formulated particle manufactured by the method for manufacturing the moutan bark formulated particle as claimed in any one of claims 1 to 9.
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| CN101491546A (en) * | 2008-01-21 | 2009-07-29 | 未名天人中药有限公司 | Traditional Chinese medicine formulation granules containing volatile oil and preparation method thereof |
| CN102114008A (en) * | 2010-01-01 | 2011-07-06 | 江苏康缘药业股份有限公司 | Clathrate of paeonol and preparation method and quality detection method thereof |
| CN103861120A (en) * | 2012-08-16 | 2014-06-18 | 湖北天圣康迪制药有限公司 | Preparation method of inclusion medicament |
| CN110841075A (en) * | 2019-11-18 | 2020-02-28 | 鲁南制药集团股份有限公司 | Preparation method of paeonol inclusion compound |
| CN110974977A (en) * | 2019-12-17 | 2020-04-10 | 成都柏睿泰生物科技有限公司 | Drying method of paeonol β -cyclodextrin inclusion compound in preparation of cortex moutan formula granules |
-
2021
- 2021-11-17 CN CN202111362056.8A patent/CN114028341A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101491546A (en) * | 2008-01-21 | 2009-07-29 | 未名天人中药有限公司 | Traditional Chinese medicine formulation granules containing volatile oil and preparation method thereof |
| CN102114008A (en) * | 2010-01-01 | 2011-07-06 | 江苏康缘药业股份有限公司 | Clathrate of paeonol and preparation method and quality detection method thereof |
| CN103861120A (en) * | 2012-08-16 | 2014-06-18 | 湖北天圣康迪制药有限公司 | Preparation method of inclusion medicament |
| CN110841075A (en) * | 2019-11-18 | 2020-02-28 | 鲁南制药集团股份有限公司 | Preparation method of paeonol inclusion compound |
| CN110974977A (en) * | 2019-12-17 | 2020-04-10 | 成都柏睿泰生物科技有限公司 | Drying method of paeonol β -cyclodextrin inclusion compound in preparation of cortex moutan formula granules |
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Application publication date: 20220211 |