CN113041311A - Preparation method of pill of six ingredients with rehmannia - Google Patents
Preparation method of pill of six ingredients with rehmannia Download PDFInfo
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- CN113041311A CN113041311A CN202110485915.6A CN202110485915A CN113041311A CN 113041311 A CN113041311 A CN 113041311A CN 202110485915 A CN202110485915 A CN 202110485915A CN 113041311 A CN113041311 A CN 113041311A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 48
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- AMBQHHVBBHTQBF-UOUCRYGSSA-N loganin Chemical compound O([C@@H]1OC=C([C@H]2C[C@H](O)[C@H](C)[C@H]21)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O AMBQHHVBBHTQBF-UOUCRYGSSA-N 0.000 description 34
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000013558 reference substance Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000010586 diagram Methods 0.000 description 11
- 235000011187 glycerol Nutrition 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
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- 206010037660 Pyrexia Diseases 0.000 description 1
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- 208000009205 Tinnitus Diseases 0.000 description 1
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- YLKUQAFDYMLBCK-UHFFFAOYSA-N butan-1-ol;ethyl acetate Chemical compound CCCCO.CCOC(C)=O YLKUQAFDYMLBCK-UHFFFAOYSA-N 0.000 description 1
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- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
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- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
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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)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
-
- 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
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
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- 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)
- A61K36/40—Cornaceae (Dogwood family)
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
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- 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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- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/884—Alismataceae (Water-plantain family)
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Abstract
The invention discloses a preparation method of a pill of six ingredients with rehmannia. The six-ingredient rehmannia pill comprises the following medicinal effective components in parts by weight: 160 parts of prepared rehmannia root, 80 parts of wine-processed cornus fruit, 60 parts of tree peony bark, 80 parts of Chinese yam, 60 parts of tuckahoe and 60 parts of rhizoma alismatis; the preparation method of the pill comprises the following steps: (1) powder: pulverizing radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria and Alismatis rhizoma, sieving, and mixing to obtain medicinal powder; (2) preparation of the adhesive: putting glycerol into a container, adding medicinal carboxymethyl cellulose salt, stirring, sealing, and heating until the carboxymethyl cellulose salt is completely swelled to obtain adhesive; (3) preparation of the pill: adding binder in an amount of 25-50% of the total amount of the prepared medicinal materials into the paste powder mixture, mixing, and making into pill. The prepared six-ingredient rehmannia pill does not use ethanol, refined honey and water as adhesives, does not need a drying process, and has the beneficial effects of less loss of a volatile component paeonol in a finished product, relatively higher content, short dispersion time limit, stable and controllable quality.
Description
Technical Field
The invention relates to a pill of six ingredients with rehmannia, in particular to a preparation method of a pill (soft pill) of six ingredients with rehmannia.
Background
The Ministry of health drug Standard WS 3-B-2102-96: LIUWEIDIHUANG pill (concentrated pill) has effects of nourishing yin and invigorating kidney, and can be used for treating kidney yin deficiency, dizziness, tinnitus, soreness of waist and knees, hectic fever, night sweat, spermatorrhea, and diabetes. The legal prescription and preparation method of pill of six ingredients with rehmannia (water-honeyed pill, small honeyed pill, honeyed pill) are recorded in the first part of 2020 edition of Chinese pharmacopoeia, and the prescription: 160g of prepared rehmannia root; 80g of wine cornus pulp; 60g of moutan bark; 80g of Chinese yam; 60g of poria cocos; 60g of rhizoma alismatis; the preparation method comprises the following steps: pulverizing the above six materials into fine powder, sieving, and mixing. Preparing pills with ethanol, drying, and preparing water pills, or adding 35-50 g of refined honey and a proper amount of water into every 100g of powder, preparing pills, drying, and preparing water-honeyed pills; or adding 80-110 g of refined honey to prepare honeyed pills.
The pill (watered pill) of six ingredients with rehmannia mainly adopts ethanol as a binder for preparing pills, the pill (watered honeyed pill or honeyed pill) of six ingredients with rehmannia mainly adopts refined honey as the binder for preparing pills, because the two auxiliary materials contain certain moisture, the pills are usually dried after being prepared, the drying temperature is between 60 and 80 ℃, the drying time is about 6 to 24 hours, the drying time is long, and because the paeonol contained in the tree peony bark in the prescription of the pill (watered pill, watered honeyed pill or honeyed pill) of six ingredients with rehmannia is easy to volatilize at about 50 ℃, a large amount of volatile components are volatilized and lost, the content of the finished product is reduced, even if the content of the paeonol in the finished product is controlled within a qualified range by various modes, the paeonol on the surface of the pill can slowly volatilize after being placed for a period of time, so that the surface of the pill has fine pores, more importantly, the content of the paeonol is reduced, affecting the quality of the medicine. In the prior art, the ' engineering research on raw material pretreatment of a pill (water-honeyed pill) of six ingredients with rehmannia ' published in 12 months in 2013 of the journal of traditional Chinese medicine ' is explained, the pill (water-honeyed pill) of six ingredients with rehmannia is used as a carrier, the engineering research is carried out on the raw material pretreatment, and each process parameter is optimized. The continuous and automatic production line integrating the advantages of cleaning, drying, vacuum pipeline conveying, low-temperature crushing, automatic mixing and the like into the raw material pretreatment process can also improve the content of paeonol, but the cost for establishing the production line is higher.
Disclosure of Invention
The invention aims to provide a preparation method of a pill of six ingredients with rehmannia. The six-ingredient rehmannia pills prepared by the method do not use ethanol, refined honey and water as adhesives, and the prepared six-ingredient rehmannia pills do not need a drying process, so that the loss of a volatile component paeonol in a finished product is less, the content is relatively high, the dispersion time limit is short, and the quality is stable and controllable.
The technical scheme of the invention is as follows: a preparation method of a pill of six ingredients with rehmannia comprises the following medicinal effective components in parts by weight: 160 parts of prepared rehmannia root, 80 parts of wine-processed cornus fruit, 60 parts of tree peony bark, 80 parts of Chinese yam, 60 parts of tuckahoe and 60 parts of rhizoma alismatis; the preparation method of the pill comprises the following steps:
(1) powder: pulverizing radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria and Alismatis rhizoma, sieving, and mixing to obtain medicinal powder;
(2) preparation of the adhesive: putting glycerol into a container, adding medicinal carboxymethyl cellulose salt, stirring, sealing, and heating until the carboxymethyl cellulose salt is completely swelled to obtain adhesive;
(3) preparation of the pill: adding binder 20-50% of the total amount of the prepared medicinal materials into the paste powder mixture, mixing, and making into pill.
The pharmaceutically acceptable carboxymethyl cellulose salt includes: sodium carboxymethyl cellulose or calcium carboxymethyl cellulose.
In the step (2), the weight ratio of glycerol to the medicinal carboxymethyl cellulose salt is 100: 1-15.
Specifically, in the step (2), the ratio by weight of glycerin to the pharmaceutically acceptable salt of carboxymethyl cellulose is 100: 2-10.
More specifically, in the step (2), glycerin is added to the pharmaceutically acceptable carboxymethyl cellulose salt at a weight ratio of 100: 2-6.
In the step (2), the heating condition is that the heating is carried out for 4 to 10 hours at the temperature of between 70 and 105 ℃.
In the step (2), the stirring is carried out once every 0.5 to 2 hours during the heating.
In the step (3), the adhesive is added in a proportion of 20-40% of the total amount of the prepared medicine.
In the step (3), the adhesive is added in a proportion of 25-35% of the total amount of the prepared medicine.
Compared with the prior art, the invention has the following beneficial effects:
the six-ingredient rehmannia pills prepared by the method do not use ethanol, refined honey and water as adhesives, and the prepared six-position rehmannia pills do not need a drying process, so that the loss of a volatile component paeonol in a finished product is less, the content is relatively high, the dispersion time limit is short, and the quality is stable and controllable.
The applicant applies the preparation technology of the soft pills to the pill of six ingredients with rehmannia, the pill of rejuvenation for children, the pill of women, the pill of medlar, chrysanthemum and rehmannia, the pill of storax and the pill of Zhibai and rehmannia, and obtains remarkable effects. The following is the relevant experimental demonstration of the Liuwei Dihuang Wan-Shuiwan. The inventors have conducted a number of tests, some of which are reported below:
[ prescription ] prepared rehmannia root 160g wine cornus 80g moutan bark 60g Chinese yam 80g poria 60g alisma orientale 60g
[ PREPARATION METHOD ] pulverizing the above six drugs into fine powder, sieving, and mixing. Preparing pills with ethanol, drying, and preparing water pills, or adding 35-50 g of refined honey and a proper amount of water into every 100g of powder, preparing pills, drying, and preparing water-honeyed pills; or adding 80-110 g of refined honey to prepare small honeyed pills or large honeyed pills.
Pill of six ingredients with rehmannia (watered pill): mixing the above materials with 50g of fine powder according to prescription standard, making into pill with 30% ethanol solution, and drying (drying at 100 deg.C for 24 hr).
Pill of six ingredients with rehmannia (water-honeyed pill): taking 50g of the mixed fine powder according to the prescription standard, adding 22.53g of refined honey and 7.41g of water, making pills, and drying (drying at the drying temperature of 100 ℃ for 24 hours) to obtain the traditional Chinese medicine composition.
Pill of six ingredients with rehmannia (big honeyed pill): taking 50.13g of the mixed fine powder according to the prescription standard, adding 40.44g of refined honey, and making into pills.
Pill of six ingredients with rehmannia (soft pill): taking 50.15g of the mixed fine powder according to the prescription standard for later use.
Preparing an adhesive: 100.04g of glycerol is taken to be put into a beaker, 4.04g of sodium carboxymethylcellulose is added to be stirred uniformly, and the mixture is heated for 5 to 7 hours at the temperature of 90 ℃ to prepare the adhesive for standby.
Adding 21.34g of adhesive into the 50.15g of mixed fine powder, uniformly mixing, and preparing into innovated pills.
[ PROPERTIES ]
1. Pill of six ingredients with rehmannia: the product is brown-black watered pill, as shown in figure 1; sweet and sour.
2. Water-honeyed pills of six ingredients with rehmannia: the product is brown-black water-honeyed pill, as shown in figure 2; sweet and sour.
3. Honeyed pills of six ingredients with rehmannia: the product is a brown to dark brown honeyed pill, as shown in figure 3; sweet and sour.
4. The prepared Liuwei Dihuang soft pills comprise the following components: the product is soft pill with brown to black brown color, as shown in figure 4; sweet and sour.
And (4) conclusion: the properties of the Liuwei Dihuang pill water-paste pill, the water-paste honeyed pill, the honeyed pill and the soft pill all accord with the specification, and compared with the three different Liuwei Dihuang pill formulations, the soft pill has no difference in properties and accords with the specification.
[ IDENTIFICATION ]
1. Morroniside and loganin
Preparing a water-bindered pill test sample: collecting 3g (3.09g) of the product, grinding, adding 25ml of methanol, performing ultrasonic treatment for 30 min, filtering, evaporating filtrate, dissolving residue with 20ml of water, shaking with n-butanol-ethyl acetate (1: 1) mixed solution for 2 times, each time 20ml, mixing extractive solutions, washing with 20ml of ammonia solution (1-10), discarding ammonia solution, evaporating n-butanol solution, dissolving residue with 1ml of methanol to obtain sample.
Preparing a water-honeyed pill test product: 4g (4.14g) of the product is taken and ground into fine powder, and the preparation method is the same as that of the water-bindered pill test sample.
Preparing a honeyed pill test product: the preparation method is the same as the preparation of the water-bindered pill test sample by taking 6g (6.07g) of the product and cutting into pieces.
Preparing a soft pill test sample: the preparation method of the product is the same as the preparation of the water-bindered pill test sample by taking 6g (6.09g) of the product and cutting into pieces.
Preparation of control: adding methanol into the morroniside control and loganin control to obtain mixed solutions each containing 2mg per 1ml as control solutions.
Temperature: 7 ℃, humidity: 72 percent;
scale model: ME204E, instrument number: HF-YF 032;
name of reference substance: morroniside, source: the Chinese food and drug testing institute;
batch number: 11998 and 201713, formulation batch: 20200924-04;
name of reference substance: loganin, source: the Chinese food and drug testing institute;
batch number: 11640 and 20180, and preparation batch number: 20200924-05;
developing agent: chloroform-methanol (3: 1), stationary phase: silica gel G;
sample amount of the test sample: 5(5 μ l), control spot size: 2 (2. mu.l);
color development conditions are as follows: spraying 10% ethanol sulfate solution (prepared lot number: S20200816-01), heating at 105 deg.C until the color of spots is clear, and inspecting under ultraviolet lamp (365 nm). In the chromatogram of the test sample, fluorescent spots of the same color appear at the positions corresponding to those of the chromatogram of the reference sample, and the thin layer images are shown in FIGS. 5 and 6, wherein the reference sample, the water-honeyed pill, the honeyed pill and the soft pill are sequentially arranged from left to right in FIG. 5, and the soft pill, the reference sample and the water-honeyed pill are sequentially arranged from left to right in FIG. 6.
And (4) conclusion: through the thin-layer identification test, the pill of six ingredients with rehmannia (soft pill) and the pill of six ingredients with rehmannia (watered pill, honeyed pill) are inspected under an ultraviolet lamp (365nm), and fluorescent spots with the same color are displayed on the positions corresponding to the chromatogram of the reference substance, and contain morroniside and loganin; compliance with the regulations.
2. Paeonol
Preparing a water-bindered pill test sample: grinding 4.5g (4.57g) of the product, adding diethyl ether 40ml, refluxing for 1 hr, filtering, volatilizing diethyl ether from the filtrate, and dissolving the residue in acetone 1ml to obtain a test solution.
Preparing a water-honeyed pill test product: taking 6g (6.08g) of the product, grinding, and preparing the same as the preparation of the water-bindered pill test sample.
Preparing a honeyed pill test product: 9g (9.11g) of the product is taken, cut into pieces, added with 4g of diatomite and ground evenly. The preparation method is the same as that of the water-bindered pill test sample.
Preparing a soft pill test sample: 9g (9.10g) of the product is taken, cut into pieces, added with 4g of diatomite and ground evenly. The preparation method is the same as that of the water-bindered pill test sample.
Preparation of control: and adding acetone into paeonol control to obtain solution containing 1mg per 1 ml.
Temperature: 6 ℃, humidity: 71 percent;
scale model: ME204E, instrument number: HF-YF 032;
name of reference substance: paeonol, source: the Chinese food and drug testing institute;
batch number: 110708-: 20201008-01;
developing agent: cyclohexane-ethyl acetate (3: 1), stationary phase: silica gel G;
sample amount of the test sample: 8 (5-10 μ l), the sample amount of a reference substance: 8 (5-10 μ l);
color development conditions are as follows: spraying hydrochloric acid 5% ferric chloride ethanol solution (preparation batch number: S20200512-07), and heating at 105 deg.C until the spots are clearly developed. Spots of the same color appear in the chromatogram of the test solution at the positions corresponding to those of the chromatogram of the reference solution, the thin layer diagram is shown in FIG. 7, and the reference solution, the honeyed pill, the water-honeyed pill, the watered pill and the soft pill are sequentially arranged from left to right in FIG. 7.
And (4) conclusion: through the thin-layer identification test, the Liuwei Dihuang pill (soft pill) and the Liuwei Dihuang pill (watered pill, water-honeyed pill or honeyed pill) can show spots with the same color on the corresponding positions of the chromatogram of the reference substance through the color development condition, and both contain paeonol; compliance with the regulations.
3. Rhizoma alismatis
Preparing a water-bindered pill test sample: grinding 4.5g (4.55g) of the product, adding 40ml of ethyl acetate, heating and refluxing for 20 minutes, cooling, filtering, and concentrating the filtrate to 0.5ml to obtain the product.
Preparing a water-honeyed pill test product: take 6g (6.23g) of this product, grind it into fine powder, and prepare the same way as the above-mentioned watered pill for testing.
Preparing a honeyed pill test product: 9g (9.17g) of the product is taken, cut into pieces, added with 4g of diatomite and ground evenly. The preparation method is the same as that of the water-bindered pill test sample.
Preparing a soft pill test sample: 9g (9.08g) of the product is taken, cut into pieces, added with 4g of diatomite and ground evenly. The preparation method is the same as that of the water-bindered pill test sample.
Preparation of control: collecting Alismatis rhizoma control 0.5g, adding ethyl acetate 40ml, heating under reflux for 20 min, cooling, filtering, and concentrating the filtrate to 0.5 ml.
Temperature: 8 ℃, humidity: 75 percent;
scale model: ME204E, instrument number: HF-YF 032;
comparing the names of the medicinal materials: rhizoma alismatis, source: the Chinese food and drug testing institute;
batch number: 121081 and 201807, formulation batch: 20201213-02;
developing agent: chloroform-ethyl acetate-formic acid (12: 7: 1), stationary phase: silica gel G;
sample amount of the test sample: 10 (5-10 μ l); sample amount of the reference sample: 10 (5-10 μ l);
color development conditions are as follows: spraying 10% sulphuric acid ethanol solution (preparation batch: S20200816-01), and heating at 105 deg.C until the spots are clearly developed. The chromatogram of the sample shows main spots of the same color at the corresponding positions of the chromatogram of the reference material, the thin layer diagram is shown in FIG. 8, and the reference material, watered pill, watered honeyed pill, and soft pill are sequentially arranged from left to right in FIG. 8.
And (4) conclusion: through the thin-layer identification test, the Liuwei Dihuang pill (soft pill) and the Liuwei Dihuang pill (watered pill, water-honeyed pill or honeyed pill) have main spots with the same color on the positions corresponding to the color spectrum of a reference substance through the color development condition, and both contain the rhizoma alismatis; compliance with the regulations.
[ EXAMINATION ]
1. Moisture content: not more than 9.0%. (Water-bindered pill)
Drying method
Temperature: 7 ℃, humidity: 72 percent;
scale model:
ME204E □MS205DU
balance number:
HF-YF032 □HF-YF033
the instrument model is as follows:
GZX-9070MBE □GZX-9240MBE
instrument numbering:
HF-YF031 □HF-YF015
drying temperature: 105 ℃, drying time: 6 h;
weighing bottle (first, g) 64.3035; weighing bottle (constant weight, g)64.3026
Sample amount (g): 3.5248, respectively;
weigh flask + sample (first, g) 67.6813; weigh flask + sample (second time, g) 67.6794;
and (3) calculating:
moisture content was measured as (64.3026+3.5248-67.6794)/3.5248 × 100% ═ 4.2%.
2. Moisture content: not more than 12.0%. (Water-honeyed pill)
Drying method
Temperature: 8 ℃, humidity: 71 percent;
scale model:
ME204E □MS205DU
balance number:
HF-YF032 □HF-YF033
the instrument model is as follows:
GZX-9070MBE □GZX-9240MBE
instrument numbering:
HF-YF031 □HF-YF015
drying temperature: 105 ℃, drying time: 6 h;
weighing bottle (first, g) 65.1432; weighing bottle (constant weight, g) 65.1421;
sample amount (g): 3.4048, respectively;
weigh flask + sample (first, g) 68.2279; weigh flask + sample (second time, g) 68.2268;
and (3) calculating:
moisture content was measured as (65.1421+3.4048-68.2268)/3.4048 × 100% ═ 9.4%.
3. Moisture content: must not exceed 15% (honeyed pill)
Toluene process
Scale model:
ME204E □MS205DU
balance number:
HF-YF032 □HF-YF033
sample amount: 14.5985 g;
amount of toluene: 201 ml;
moisture scale reading: 2.0 ml;
and (3) calculating:
moisture content determination-moisture scale reading/sample size-2.0/14.5985-100% -13.7%.
4. Moisture content: must not exceed 9 percent (Soft pill)
Toluene process
Scale model:
ME204E □MS205DU
balance number:
HF-YF032 □HF-YF033
sample amount: 30.4679 g;
amount of toluene: 200 ml;
moisture scale reading: 2.4 ml;
and (3) calculating:
moisture content determination-moisture scale reading/sample size-100% (2.4/30.4679) -7.88%.
And (4) conclusion: the water content of the pill (watered pill, watered honeyed pill, and soft pill) is determined to meet the specification; the result shows that the water content of the soft pills is obviously lower than that of the honeyed pills. Thus, the moisture content of the soft pills is lower than that of the honeyed pills.
5. Dissolution time limit: complete dissolution should be achieved within 1 hour. (Water-bindered pill)
Temperature: 9 ℃, humidity: 68 percent;
the appearance that disintegrates intelligently:
ZB-ID Instrument number:
HF-YF017
water temperature: 37 ℃, disintegration solvent: water;
complete disintegration time: 48min, see FIG. 9.
6. Dissolution time limit: complete dissolution should be achieved within 1 hour. (Water-honeyed pill)
Temperature: 6 ℃, humidity: 68 percent;
the appearance that disintegrates intelligently:
ZB-ID Instrument number:
HF-YF017
water temperature: 37 ℃, disintegration solvent: water;
complete disintegration time: 40min, see FIG. 10.
7. Dissolution time limit: complete dissolution should be achieved within 1 hour. (Soft pill)
Temperature: 7 ℃, humidity: 68 percent;
the appearance that disintegrates intelligently:
ZB-ID Instrument number:
HF-YF017
water temperature: 37 ℃, disintegration solvent: water;
complete disintegration time: 25min, see FIG. 11.
And (4) conclusion: through disintegration time limit experiments, the disintegration time limit of the flexible pills is much less than that of water-paste pills and water-honeyed pills, and the flexible pills are easier to disintegrate, so that the disintegration time limit of the patent pills is superior to that of the water-paste pills and the water-honeyed pills.
Content determination:
measuring by high performance liquid chromatography (Chinese pharmacopoeia).
Temperature: 9 ℃, humidity: 65 percent;
scale model:
ME204E □ MS205DU balance number:
HF-YF032 □HF-YF033
the instrument model is as follows: □ HF-YF038 □ HF-YF028
HF-YF029
Instrument numbering: □ LC-Ultimate3000 □ LC-30AD
Agilent1260
A chromatographic column: specification: 4.6mm by 250 mm;
flow rate: 1ml/min, column temperature: 40 ℃;
name of reference substance: the sources of the morroniside, loganin and paeonol reference substances are as follows: china institute for testing and testing food and medicine
Morroniside control lot number: 11998-; control solution preparation batch number: 20200823, respectively;
loganin control batch number: 111640-201808; control solution preparation batch number: 20200726, respectively;
batch number of paeonol reference substance: 110708-; control solution preparation batch number: 20200625, respectively;
chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile is taken as a mobile phase A, 0.3 percent phosphoric acid solution is taken as a mobile phase B, and gradient elution is carried out according to the specification in the following table; the detection wavelength of the morroniside and loganin is 240nm, and the detection wavelength of the paeonol is 274 nm; the column temperature was 40 ℃. The number of theoretical plates should be not less than 4000 in terms of morroniside and loganin peaks, and the flow gradient is shown in Table 1.
TABLE 1
Preparation of control solutions: taking appropriate amount of morroniside reference substance, loganin reference substance and paeonol reference substance, precisely weighing, and adding 50% methanol to obtain mixed solution containing morroniside and loganin 20 μ g each and paeonol 45 μ g each per 1 ml.
Preparing a water-bindered pill test solution: grinding the product, precisely weighing about 0.5g, placing into a conical flask with a plug, precisely adding 25ml of 50% methanol, sealing the plug, weighing, heating and refluxing for 1 hr, cooling, weighing again, supplementing the lost weight with 50% methanol, shaking, filtering, and collecting the subsequent filtrate.
Preparing a test solution of water-honeyed pills: grinding the product into fine powder, weighing about 0.7g, and preparing into the same preparation as the above watered pill test solution.
Preparing a honeyed pill test solution: cutting the product into pieces, weighing about 1.0g, and preparing into the same preparation as the above watered pill test solution.
Preparing a flexible pill test solution: cutting the product into pieces, weighing about 1.0g, and preparing into the same preparation as the above watered pill test solution.
The determination method comprises the following steps: precisely sucking 10 μ l of the reference solution and the sample solution, respectively, injecting into a liquid chromatograph, and measuring.
Each pill contains morroniside (C) extracted from fructus Corni17H26O11) And loganin (C)17H26O10) Not less than 0.9mg per 1 g; cortex moutan and paeonol (C)9H10O3) Calculated per 1g, not less than 1.3mg。
Morroniside weighing amount: 10.17mg, concentration: 0.0198112 mg/ml;
weighing loganin: 11.31mg, concentration: 0.0223938 mg/ml;
weighing paeonol: 10.47mg, concentration: 0.05235 mg/ml;
control peak area (m): 306.759, respectively; control peak area 2 (m): 312.151, respectively; control peak area (m): 310.309, respectively; peak area of control (m): 311.713, respectively; control peak area (m): 306.971, respectively;
control peak area (r) (horse): 354.905, respectively; control peak area — (horse): 354.929, respectively; control peak area (c) (horse): 359.517, respectively; peak area of control (horse): 355.066, respectively; control peak area (horse): 353.429.
comparison peak area (red): 2309.2976, respectively; control peak area (dan): 2290.2751, respectively; comparison peak area (red): 2312.5757, respectively; peak area of control (d): 2311.9835, respectively; control peak area (dan): 2313.4534.
average peak area of control
(m): 309.5806, respectively;
average peak area of control
(horse): 355.5692, respectively;
average peak area of control
(pellet): 2307.51634.
dilution times are as follows: 25;
weighing a water pill sample firstly: 0.5263 g; water pill sample weighing: 0.508 g;
peak area (Moh) of water pill test sample: 69.057, respectively; peak area (Moh) of water pill sample II: 62.8065, respectively;
area of the test sample (horse): 346.395, respectively; area of the water pill sample 2 (horse): 318.8975, respectively;
the peak area (pellet) of the water pill test sample is as follows: 1094.0875, respectively; the water pill sample 2 has peak area (pellet): 1048.5406.
weighing sample quantities of water-honeyed pills: 0.7279 g; weighing sample amount of water-honeyed pills: 0.7321 g;
peak areas (Moh) of water-honeyed pills: v,; peak area (Moh) of water-honeyed pill: v,;
peak areas (horse) of water-honeyed pills: 367.9625, respectively; peak area of water-honeyed pill (horse): 340.978, respectively;
the peak areas (pellet) of the water-honeyed pills: 895.72965, respectively; water honeyed pill sample 2 peak area (pellet): 877.88495, respectively;
weighing honeyed pills: 1.0191 g; honeyed pill sample 2, weighing: 1.0314 g;
peak area (Mo) of honeyed pill: 136.152, respectively; honeyed pill sample 2 peak area (mo): 124.0155, respectively;
peak areas (horse) of honeyed pills: 386.7435, respectively; honeyed pill sample 2 peak area (horse): 361.201, respectively;
the peak areas (pellet) of the honeyed pills: 1967.0012, respectively; honeyed pill sample 2 peak area (pellet): 1928.75, respectively;
weighing a flexible pill sample firstly: 1.0055 g; weighing a flexible pill sample II: 1.0809 g;
peak area (Moh) of flexible pill test sample: 179.7325, respectively; flexible pill sample 2 peak area (Moh): 192.422, respectively;
peak area of the soft pill sample (horse): 497.517, respectively; area of the soft pill sample II (horse): 599.918, respectively;
the peak area (pellet) of the soft pill test sample is as follows: 2307.8118, respectively; flexible pill sample 2 peak area (pellet): 2514.56285. (the chromatogram of injection is shown in FIGS. 12-47, wherein the chromatogram of determination of the contents of morroniside and loganin is shown in FIGS. 12-29, and the chromatogram of determination of the content of paeonol is shown in FIGS. 30-47.)
And (3) calculating: the pill powder proportion data is shown in table 2;
TABLE 2 pill powder ratio data sheet
And (3) measuring and calculating the content of the morroniside: (a-sample-C-control-dilution factor)/(a-pair average-number-W-sample)/powder ratio;
honeyed pills 1: (136.152 × 0.0198112 × 25)/(309.5806 × 1.0191)/0.553494535 ═ 0.386mg/g
And (3) honeyed pills 2: (124.0155 × 0.0198112 × 25)/(309.5806 × 1.0314)/0.553494535 ═ 0.348mg/g
Honeyed pill (average content): (0.386+0.348)/2 ═ 0.367 mg/g.
Flexible pill 1: (179.7325 × 0.0198112 × 25)/(309.5806 × 1.0055)/0.701496713 ═ 0.408mg/g
And (2) flexible pill: (192.422 × 0.0198112 × 25)/(309.5806 × 1.0809)/0.701496713 ═ 0.406mg/g
Pliable pill (average content): (0.408+0.406)/2 ═ 0.407 mg/g.
1, water pill: (69.057 × 0.0198112 × 25)/(309.5806 × 0.5263) ═ 0.210mg/g
2, water pills: (62.8065 × 0.0198112 × 25)/(309.5806 × 0.508) ═ 0.198mg/g
Watered pill (average content): (0.21+ 0.198)/2-0.204 mg/g.
1, water-honeyed pill: not detected out
And (3) water-honeyed pills 2: it was not detected.
And (3) measuring and calculating the loganin content: (a-sample-C-control-dilution factor)/(a-pair average-number-W-sample)/powder ratio;
honeyed pills 1: (386.7435 × 0.223938 × 25)/(355.5692 × 1.0191)/0.553494535 ═ 1.078mg/g
And (3) honeyed pills 2: (361.201 × 0.223938 × 25)/(355.5692 × 1.0314)/0.553494535 ═ 0.996mg/g
Honeyed pill (average content): (1.078+0.996)/2 ═ 1.037 mg/g.
Flexible pill 1: (497.517 × 0.223938 × 25)/(355.5692 × 1.0055)/0.701496713 ═ 1.104mg/g
And (2) flexible pill: (599.918 × 0.223938 × 25)/(355.5692 × 1.0809)/0.701496713 ═ 1.246mg/g
Pliable pill (average content): (1.104+1.246)/2 ═ 1.175 mg/g.
1, water pill: (346.395 × 0.223938 × 25)/(355.5692 × 0.5263) ═ 1.036mg/g
2, water pills: (497.517 × 0.223938 × 25)/(355.5692 × 0.508) ═ 0.988mg/g
Watered pill (average content): (1.036+0.988)/2 ═ 1.012 mg/g.
1, water-honeyed pill: (367.96255 × 0.223938 × 25)/(355.5692 × 0.7279)/0.723060571 ═ 1.101mg/g
And (3) water-honeyed pills 2: (340.978 × 0.223938 × 25)/(355.5692 × 0.7321)/0.723060571 ═ 1.014mg/g
Water-honeyed pill (average content): (1.101+ 1.014)/2-1.0575 mg/g.
And (3) measuring and calculating the content of paeonol: (a-sample-C-control-dilution factor)/(a-pair average-number-W-sample)/powder ratio;
honeyed pills 1: (1967.0012 × 0.05235 × 25)/(2307.51634 × 1.0191)/0.553494535 ═ 1.978mg/g
And (3) honeyed pills 2: (1928.75 × 0.05235 × 25)/(2307.51634 × 1.0314)/0.553494535 ═ 1.915mg/g
Honeyed pill (average content): (1.978+1.915)/2 ═ 1.9465mg/g
Flexible pill 1: (2307.8118 × 0.05235 × 25)/(2307.51634 × 1.0055)/0.701496713 ═ 1.856mg/g
And (2) flexible pill: (2514.56285 × 0.05235 × 25)/(2307.51634 × 1.0809)/0.701496713 ═ 1.881mg/g
Pliable pill (average content): (1.856+1.881)/2 ═ 1.8685 mg/g.
1, water pill: (1094.0875 × 0.05235 × 25)/(2307.51634 × 0.5263) ═ 1.179mg/g
2, water pills: (1048.5406 × 0.05235 × 25)/(2307.51634 × 0.508) ═ 1.171mg/g
Watered pill (average content): (1.179+ 1.171)/2-1.175 mg/g.
1, water-honeyed pill: (895.72965 × 0.05235 × 25)/(2307.51634 × 0.7279)/0.723060571 ═ 0.965mg/g
And (3) water-honeyed pills 2: (877.88495 × 0.05235 × 25)/(2307.51634 × 0.7321)/0.723060571 ═ 0.941mg/g
Water-honeyed pill (average content): (0.965+0.941)/2 ═ 0.953 mg/g.
And (4) conclusion: through the content determination, the contents of the honeyed pills and the soft pills meet the standard; the volatile component paeonol in the content determination of the water-honeyed pills and the water-honeyed pills is unqualified; after various dosage forms are compared, the contents of all components of the soft pills are higher than those of water-honeyed pills and are not much different from those of the honeyed pills.
In conclusion, the prepared pill of six ingredients with rehmannia does not use ethanol, refined honey and water as adhesives, and the prepared pill of six ingredients with rehmannia does not need a drying process, so that the loss of a volatile component paeonol in a finished product is less, the content is relatively high, the dispersion time limit is short, and the quality is stable and controllable.
Drawings
FIG. 1 is a diagram of a LIUWEIDIHUANG watered pill in the properties proved by the experiment of the present invention;
FIG. 2 is a diagram of a water-honeyed pill of six ingredients with rehmannia for testing and proving properties of the invention;
FIG. 3 is a diagram of a six-ingredient rehmannia pill honeyed pill for testing and proving properties of the invention;
FIG. 4 is a diagram of the present invention experiment demonstrating flexible pill (Liuwei Dihuang pill prepared by the present invention) in the character;
FIG. 5 is a thin-layer diagram of the invention for testing and identifying morroniside and loganin, wherein the thin-layer diagram sequentially comprises a reference substance, a water-honeyed pill, a honeyed pill and a soft pill from left to right;
FIG. 6 is a thin-layer diagram of morroniside and loganin in the assay of the present invention, wherein the sequence from left to right is a soft pellet, a control, and a watered pill;
FIG. 7 is a thin-layer diagram of paeonol in the invention identification, wherein the comparison product, the honeyed pill, the water-honeyed pill, the watered pill and the soft pill are sequentially arranged from left to right;
FIG. 8 is a thin-layer diagram of Alisma orientale in the test proof-identification of the present invention, wherein the control, the watered pill, the honeyed pill and the soft pill are sequentially arranged from left to right;
FIG. 9 is a graph showing the disintegration test of LIUWEIDIHUANG watered pill in the dissolution time limit of the present invention;
FIG. 10 is a test chart showing the disintegration of a water-honeyed pill of six ingredients with rehmannia in the dissolution time limit, which is proved by the experiment of the present invention;
FIG. 11 is a graph showing the experimental demonstration of the disintegration of the soft-shelled turtle (pill of six ingredients with rehmannia) in the dissolution time limit according to the present invention;
FIG. 12 is a chromatogram for determining the content of a reference substance in the determination of the content of morroniside and loganin according to the experimental demonstration of the present invention;
FIG. 13 is a chromatogram for determining the content of a reference substance in the determination of the content of morroniside and loganin according to the experimental demonstration of the present invention;
FIG. 14 is a chromatogram for determining the content of a honeyed pill in the determination of the content of morroniside and loganin, which is proved by the experiment of the invention;
FIG. 15 is a chromatogram for determining the content of a honeyed pill in the determination of the content of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 16 is a chromatogram for determining the content of a honeyed pill in the determination of the content of morroniside and loganin, which is proved by the experiment of the invention;
FIG. 17 is a chromatogram for determining the content of a honeyed pill in the determination of the content of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 18 is a chromatogram for determining the contents of morroniside and loganin in water-honeyed pill samples, which is proved by the experiment of the present invention;
FIG. 19 is a chromatogram for determining the contents of morroniside and loganin in water-honeyed pill according to the present invention;
FIG. 20 is a chromatogram for determining the contents of morroniside and loganin in water-honeyed pill according to the present invention;
FIG. 21 is a chromatogram for determining the contents of morroniside and loganin in water-honeyed pill according to the present invention;
FIG. 22 is a chromatogram for determining the content of a pill sample in the determination of the contents of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 23 is a chromatogram for determining the content of a pill sample in the determination of the contents of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 24 is a chromatogram for determining the content of a pill sample in the determination of the contents of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 25 is a chromatogram for determining the content of a pill sample in the determination of the contents of morroniside and loganin, which is proved by the experiment of the present invention;
FIG. 26 is a chromatogram for measuring the content of a soft-shelled turtle (pill of six ingredients with rehmannia prepared by the present invention) in the assay of the morroniside and loganin content, which is proved by the present invention;
FIG. 27 is a chromatogram for measuring the content of a soft-shelled turtle (pill of six ingredients with rehmannia prepared by the present invention) in the assay of the morroniside and loganin content, which is proved by the present invention;
FIG. 28 is a chromatogram for measuring the content of a soft-shelled turtle (pill of six ingredients with rehmannia prepared by the present invention) in the assay of the morroniside and loganin content, which is proved by the present invention;
FIG. 29 is a chromatogram for measuring the content of a soft-shelled turtle (pill of six ingredients with rehmannia prepared by the present invention) in the assay of the morroniside and loganin content, which is proved by the present invention;
FIG. 30 is a chromatogram for determining the content of a reference substance in the determination of paeonol content, which is proved by experiments of the present invention;
FIG. 31 is a chromatogram for determining the content of a reference substance in the determination of paeonol content, which is proved by experiments of the present invention;
FIG. 32 is a chromatogram for determining the contents of honeyed pills in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 33 is a chromatogram for determining the content of a honeyed pill in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 34 is a chromatogram for determining the contents of honeyed pills in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 35 is a chromatogram for determining the contents of honeyed pills in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 36 is a chromatogram for determining the content of a sample, namely a water-honeyed pill, in the determination of paeonol content, according to the present invention;
FIG. 37 is a chromatogram for determining the content of a sample, a water-honeyed pill, in the determination of paeonol content, according to the present invention;
FIG. 38 is a chromatogram for determining the contents of water-honeyed pills for determination of paeonol content, which is proved by the present invention;
FIG. 39 is a chromatogram for determining the content of a sample, namely a water-honeyed pill, in the determination of paeonol content, according to the present invention;
FIG. 40 is a chromatogram for determining the content of a test sample of a pill in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 41 is a chromatogram for determining the content of a test sample of a pill in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 42 is a chromatogram for determining the content of a test sample of a pill in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 43 is a chromatogram for determining the content of a test sample of a pill in the determination of paeonol content, which is proved by the experiment of the present invention;
FIG. 44 is a chromatogram for measuring the content of a soft capsule (LIUWEIDIHUANG pill prepared by the present invention) in the measurement of paeonol content, which is proved by the present invention;
FIG. 45 is a chromatogram for measuring the content of a soft capsule (LIUWEIDIHUANG pill prepared by the present invention) in the measurement of paeonol content, which is proved by the present invention;
FIG. 46 is a chromatogram for measuring the content of a soft capsule (LIUWEIDIHUANG pill prepared by the present invention) in the measurement of paeonol content, which is shown in the present invention;
FIG. 47 is a chromatogram for measuring the content of a soft capsule (LIUWEIDIHUANG pill) in the present invention.
Detailed Description
The invention is further illustrated by the following figures and examples, which are not to be construed as limiting the invention.
Example 1. A preparation method of a pill of six ingredients with rehmannia comprises the following steps:
(1) powder: according to the prescription of the pill of six ingredients with rehmannia, 160g of prepared rehmannia root, 80g of wine-processed cornus, 60g of tree peony bark, 80g of Chinese yam, 60g of tuckahoe and 60g of alisma orientale, crushing, sieving and uniformly mixing to obtain medicinal powder;
(2) adhesive: adding 100g of glycerol into a container according to the weight ratio, then adding 4g of carboxymethylcellulose calcium, uniformly stirring, heating for 5-7 hours at 90 ℃ until the carboxymethylcellulose calcium is completely swelled, and stirring once every 1.5 hours to prepare the adhesive for later use;
(3) pill of six ingredients with rehmannia: adding adhesive in the amount of 29% of the total amount of the prepared medicinal materials into the medicinal powder mixture, mixing, and making into pill.
Example 2. A preparation method of a pill of six ingredients with rehmannia comprises the following steps:
(1) powder: preparing a powder according to the method described in example 1;
(2) adhesive: adding 100g of glycerol into a container according to the weight ratio, then adding 10 parts of sodium carboxymethylcellulose, uniformly stirring, heating at 70 ℃ for 9-10 hours until the sodium carboxymethylcellulose is completely swelled, and stirring once every 0.5 hour to prepare an adhesive for later use;
(3) pill of six ingredients with rehmannia: adding binder 20% of the total amount of the prepared medicinal materials into the medicinal powder, mixing, and making into pill.
Example 3. A preparation method of a pill of six ingredients with rehmannia comprises the following steps:
(2) (1) medicinal powder: preparing a powder according to the method described in example 1;
(2) adhesive: adding 100g of glycerol into a container according to the weight ratio, then adding 2g of sodium carboxymethylcellulose, uniformly stirring, heating for 6-7 hours at 90 ℃ until the sodium carboxymethylcellulose is completely swelled, and stirring once every 2 hours to prepare an adhesive for later use;
(3) pill of six ingredients with rehmannia: adding adhesive in an amount of 50% of the total amount of the prepared medicinal materials into the medicinal powder mixture, mixing, and making into pill.
Example 4. A preparation method of a pill of six ingredients with rehmannia comprises the following steps:
(1) powder: preparing a powder according to the method described in example 1;
(2) adhesive: adding 100g of glycerol into a container according to the weight ratio, then adding 6g of sodium carboxymethylcellulose, uniformly stirring, heating for 8-9 hours at the temperature of 80 ℃ until the sodium carboxymethylcellulose is completely swelled, and stirring once every 1 hour to prepare an adhesive for later use;
(3) pill of six ingredients with rehmannia: adding binder 40% of the total amount of the prepared medicinal materials into the medicinal powder mixture, mixing, and making into pill.
Example 5. A preparation method of a pill of six ingredients with rehmannia comprises the following steps:
(1) powder: preparing a powder according to the method described in example 1;
(2) adhesive: adding 100g of glycerol into a container according to the weight ratio, then adding 5g of carboxymethylcellulose calcium, uniformly stirring, heating for 4-5 hours at 105 ℃ until the carboxymethylcellulose calcium is completely swelled, and stirring once every 1.5 hours to prepare the adhesive for later use;
(3) pill of six ingredients with rehmannia: adding adhesive in an amount of 30% of the total amount of the prepared medicinal materials into the medicinal powder mixture, mixing, and making into pill.
Claims (9)
1. A preparation method of pills of six ingredients with rehmannia is characterized by comprising the following steps: the six-ingredient rehmannia pill comprises the following medicinal effective components in parts by weight: 160 parts of prepared rehmannia root, 80 parts of wine-processed cornus fruit, 60 parts of tree peony bark, 80 parts of Chinese yam, 60 parts of tuckahoe and 60 parts of rhizoma alismatis; the preparation method of the pill comprises the following steps:
(1) powder: pulverizing radix rehmanniae Preparata, Corni fructus, cortex moutan, rhizoma Dioscoreae, Poria and Alismatis rhizoma, sieving, and mixing to obtain medicinal powder;
(2) preparation of the adhesive: putting glycerol into a container, adding medicinal carboxymethyl cellulose salt, stirring, sealing, and heating until the carboxymethyl cellulose salt is completely swelled to obtain adhesive;
(3) preparation of the pill: adding binder 20-50% of the total amount of the prepared medicinal materials into the paste powder mixture, mixing, and making into pill.
2. The method for preparing LIUWEIDIHUANG pill as claimed in claim 1, wherein: the pharmaceutically acceptable carboxymethyl cellulose salt includes: sodium carboxymethyl cellulose or calcium carboxymethyl cellulose.
3. The method for preparing LIUWEIDIHUANG pill as claimed in claim 1, wherein: in the step (2), the weight ratio of glycerol to the medicinal carboxymethyl cellulose salt is 100: 1-15.
4. The method for preparing LIUWEIDIHUANG pill as claimed in claim 3, wherein: in the step (2), the weight ratio of glycerol to the medicinal carboxymethyl cellulose salt is 100: 2-10.
5. The method for preparing LIUWEIDIHUANG pill as claimed in claim 4, wherein: in the step (2), the weight ratio of glycerol to the medicinal carboxymethyl cellulose salt is 100: 2-6.
6. The method for preparing LIUWEIDIHUANG pill as claimed in claim 1, wherein: in the step (2), the heating condition is that the heating is carried out for 4 to 10 hours at the temperature of between 70 and 105 ℃.
7. The method for preparing LIUWEIDIHUANG pill as claimed in claim 1, wherein: in the step (2), the stirring is carried out once every 0.5 to 2 hours during the heating.
8. The method for preparing LIUWEIDIHUANG pill as claimed in claim 1, wherein: in the step (3), the adhesive is added in a proportion of 20-40% of the total amount of the prepared medicine.
9. The method for preparing LIUWEIDIHUANG pill according to claim 8, wherein: in the step (3), the adhesive is added in a proportion of 25-35% of the total amount of the prepared medicine.
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Non-Patent Citations (1)
| Title |
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| 李峰: "《中药鉴定学》", 30 April 2020, 中国医药科技出版社 * |
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Application publication date: 20210629 |