CN110721216A - Sugar-free lamiophlomis rotata oral liquid preparation and preparation method thereof - Google Patents

Abstract

The invention discloses a sugar-free lamiophlomis rotata oral liquid preparation, which relates to the field of pharmacy, wherein each 1000ml lamiophlomis rotata oral liquid comprises the following components: 400-600 g of lamiophlomis rotata, 20-40 g of xylitol, 1-2 g of potassium sorbate and the balance of purified water, and the preparation is only added with xylitol and a small amount of preservative, so that the preparation is more suitable for diabetics with symptoms of incision pain, bleeding, traumatic fracture, muscle and bone sprain, rheumatic arthralgia, metrorrhagia, dysmenorrhea, gingival swelling and pain, bleeding and the like after surgical operation, and has the effects of activating blood, relieving pain, removing blood stasis and stopping bleeding.

Description

Sugar-free lamiophlomis rotata oral liquid preparation and preparation method thereof

Technical Field

The invention belongs to the field of pharmacy, and particularly relates to a sugar-free lamiophlomis rotata oral liquid preparation and a preparation method thereof.

Background

Lamiophlomis rotata, the name of traditional Chinese medicine. Is root, rhizome or whole plant of Lamiophlomis rotate (Benth.) kudo of Labiatae. Has effects of promoting blood circulation, removing blood stasis, and relieving swelling and pain. Can be used for treating traumatic injury, arthralgia and myalgia, joint swelling and pain, dysmenorrhea, and metrorrhagia. The products on the market have lamiophlomis rotata capsules and lamiophlomis rotata tablets, but the products have a plurality of problems; the bioavailability is not high; poor drug stability; small distribution area in gastrointestinal tract and large irritation; poor flowability, non-uniform size, and difficult dose division or coating; the disintegration time is long, the dissolution speed is slow, the dosage is large and the like, and the quality and the curative effect of the medicine are directly influenced. The lamiophlomis rotata oral liquid preparation has a prescription consisting of lamiophlomis rotata single medicinal materials, changes the traditional dosage forms of tablets, capsules, granules and the like, is an oral liquid which is more convenient to use, most of the oral liquids are added with cane sugar and other flavoring agents for improving the taste at present, and cannot be taken by diabetics.

Disclosure of Invention

The invention aims to provide a sugar-free lamiophlomis rotata oral liquid preparation and a preparation method thereof, which are suitable for diabetics to take and have the effects of promoting blood circulation, relieving pain, removing blood stasis and stopping bleeding.

In order to achieve the above purpose, the invention adopts the technical scheme that: a sugar-free radix Lamiophlomidis Rotatae oral liquid preparation comprises the following components per 1000ml of radix Lamiophlomidis Rotatae oral liquid: 400-600 g of lamiophlomis rotata, 20-40 g of xylitol, 1-2 g of potassium sorbate and the balance of purified water.

In order to further optimize the present invention, the following technical solutions may be preferably selected:

preferably, each 1000ml of the lamiophlomis rotata oral liquid comprises the following components: 500g of lamiophlomis rotata, 30g of xylitol, 2g of potassium sorbate and the balance of purified water.

A method for preparing sugar-free lamiophlomis rotata oral liquid preparation comprises the following steps:

step A: cleaning and selecting the ingredients, namely removing impurities from the lamiophlomis rotata according to the proportion of the ingredients, chopping, and crushing and screening by adopting a screening machine with 10 meshes for later use;

and B: extracting and concentrating, adding 15 times of equivalent water, heating to about 45 ℃, adding the lamiophlomis rotata medicinal material cleaned and selected in the step A, soaking for 2 hours, filtering to obtain a filtrate a and a filter residue b, adding 12 times of equivalent water into the filter residue b, soaking for 2 hours, filtering to obtain a filtrate c, then combining the filtrate a and the filtrate c into a filtrate d, and concentrating the filtrate d into a clear paste with the relative density of 1.10-1.15 under the conditions of the temperature of 65-75 ℃ and the vacuum degree of 0.06-0.08Mpa, wherein the temperature is 70 ℃;

step C, adding 95% ethanol into the clear paste prepared in the step B to enable the ethanol content to reach 60% -80%, standing for 24 hours, filtering, and then recovering the ethanol until the relative density is 1.20-1.25 and the temperature is 70 ℃;

d, preparing a liquid, namely adding potassium sorbate into the filtrate obtained in the step C, stirring to dissolve the potassium sorbate, adding purified water to adjust the total amount to 1000ml, stirring uniformly, and filtering to obtain a reddish brown clear liquid; then filling 10ml of each bottle, sealing by a gland, and sterilizing in steam at 100 ℃ for 30 minutes.

The invention has the beneficial effects that:

1. the invention is a pure traditional Chinese medicine preparation, only adds xylitol and a small amount of preservative, is more suitable for diabetics with symptoms of incision pain, bleeding, traumatic fracture, sprain of muscles and bones, rheumatic arthralgia, metrorrhagia, dysmenorrhea, swelling and aching of gum, bleeding and the like after surgical operation, and is suitable for diabetics.

2. The oral liquid is convenient for children, the old and some special patients with dysphagia to take.

3. In the production process, the traditional method is used for water extraction to obtain the components of total flavone, iridoid glycoside, luteolin and the like which are easy to dissolve in water, and then ethanol is added for standing to further remove impurities, so that the extraction rate of the effective components is improved, and the method is suitable for large-scale production.

Detailed Description

Lamiophlomis rotata, the name of traditional Chinese medicine. Is root, rhizome or whole plant of Lamiophlomis rotate (Benth.) kudo of Labiatae. Has effects of promoting blood circulation, removing blood stasis, and relieving swelling and pain. Can be used for treating traumatic injury, arthralgia and myalgia, joint swelling and pain, dysmenorrhea, and metrorrhagia. The pharmacological actions of lamiophlomis rotata comprise: 1) effect on immune function: the lamiophlomis rotata saponin 500 mg/(kg d), lamiophlomis rotata alcohol extract is injected into the abdominal cavity of tumor-bearing mice by 300 mg/(kg d) or 150 mg/(kg d), and the injection lasts for 10 days, which has obvious inhibiting effect on transplanted tumor EC and saponin on Hep solid tumor strains. The same dose of saponin can be continuously administered to S180 sarcoma mouse for 12 days, and has certain therapeutic effect. The saponin can also increase spleen weight, thymus weight and body weight of tumor-bearing mice to a certain extent. Saponins extracted from the lamiophlomis rotata extract are 50 mg/(kg.d) and 100 mg/(kg.d), and are continuously injected into the abdominal cavity of an animal for 5d, so that the phagocytosis rate and the phagocytosis index of macrophages, the formation rate of E-rosettes and the positive rate of esterase staining are all obviously improved, and the lamiophlomis rotata has the function of obviously improving nonspecific immunity and specific cellular immunity.

2) The analgesic effect is as follows: the lamiophlomis rotata extract with the concentration of 10 percent is used for gastric lavage of mice with the concentration of 0.28ml/10g and the concentration of 0.14ml/10g, has obvious analgesic effect and lasts for about 2 hours. The extract can also obviously inhibit the acetic writhing reaction of mice, and the analgesic effect of 0.19-3.0g/kg is equivalent to that of 0.23g/kg aspirin.

3) Hemostasis effect: in a mouse tail vein hemostasis experiment, the 10 percent and 5 percent extractum are respectively 0.14ml/10g for intragastric administration to a mouse, and the hemostatic effect is obvious. The lamiophlomis rotata has a local hemostatic effect on incised wounds of the liver of a rat.

4) The antibacterial effect is as follows: the Lamiophlomis rotate extract has antibacterial effect on beta hemolytic streptococcus and aerobacter in filter paper sheet method. The lamiophlomis rotata saponin has obvious bacteriostatic action on dysentery bacillus, pseudomonas aeruginosa, aerobacter, bacillus subtilis and beta hemolytic streptococcus.

Example 1

The preparation method of the sugar-free lamiophlomis rotata oral liquid comprises the following steps:

step (1): removing impurities from 0.5kg of radix Lamiophlomidis Rotatae, cutting, and pulverizing with 10 mesh sieve.

Step (2): heating 15 times of water according to the prescription amount to about 45 ℃, adding the lamiophlomis rotata medicinal materials, soaking for 2 hours, filtering, storing filtrate, adding 12 times of water into filter residues, soaking for two hours, filtering, combining the filtrate, and concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15 at 70 ℃ under the conditions that the temperature is 65-70 ℃ and the vacuum degree is 0.06-0.08 Mpa;

and (3): adding ethanol to make ethanol content reach 60%, stirring, standing for 24 hr, filtering, and recovering ethanol from the filtrate to relative density of 1.20-1.25 (70 deg.C);

and (4): preparing 15% simple syrup from 30g of xylitol and 2g of potassium sorbate, stirring for dissolving, adding water to adjust the total amount to 1000ml, stirring, filtering, filling, and sterilizing to obtain the red-brown clear liquid oral liquid.

Example 2

The preparation method of the sugar-free lamiophlomis rotata oral liquid comprises the following steps:

(1) removing impurities from 0.5kg of radix Lamiophlomidis Rotatae, cutting, and pulverizing with 10 mesh sieve.

(2) Heating 15 times of water to 45 deg.C, adding radix Lamiophlomidis Rotatae, soaking for 2 hr, filtering, storing the filtrate, adding 12 times of water into the residue, soaking for two hr, filtering, mixing filtrates, and concentrating (temperature 65-70 deg.C, vacuum degree 0.06-0.08 Mpa) to obtain fluid extract with relative density of 1.10-1.15 (70 deg.C).

(3) Adding ethanol to ethanol content of 70%, stirring, standing for 24 hr, filtering, recovering ethanol from the filtrate to relative density of 1.20-1.25 (70 deg.C),

(4) preparing 20% simple syrup from 40g xylitol and 2g potassium sorbate, stirring for dissolving, adding water to adjust total amount to 1000ml, stirring, filtering, packaging, and sterilizing to obtain red brown clear liquid oral liquid.

Example 3

The preparation method of the sugar-free lamiophlomis rotata oral liquid comprises the following steps:

(1) removing impurities from 0.5kg of radix Lamiophlomidis Rotatae, cutting, and pulverizing with 10 mesh sieve.

(2) Heating 15 times of water to 45 deg.C, adding radix Lamiophlomidis Rotatae, soaking for 2 hr, filtering, storing the filtrate, adding 12 times of water into the residue, soaking for two hr, filtering, mixing filtrates, and concentrating (temperature 65-70 deg.C, vacuum degree 0.06-0.08 Mpa) to obtain fluid extract with relative density of 1.10-1.15 (70 deg.C).

(3) Adding ethanol to make ethanol content reach 80%, stirring, standing for 24 hr, filtering, recovering ethanol from filtrate to relative density of 1.20-1.25 (70 deg.C),

(4) preparing 30% simple syrup from 60g of xylitol and 2g of potassium sorbate, stirring for dissolving, adding water to adjust the total amount to 1000ml, stirring, filtering, filling, and sterilizing to obtain the red-brown clear liquid oral liquid.

The method for measuring the effective substances of the lamiophlomis rotata extract comprises the following steps:

measuring moisture according to the operation rule of the moisture measuring instrument, starting the calibrated moisture measuring instrument, weighing 10g of sampling particles, uniformly pouring the sampling particles into a scale pan, starting a balance and an infrared lamp to heat the sample, reading and recording data when the scale on the projection screen moves and is static, wherein the moisture content of the sample is obtained, and the measured moisture meets the requirement. (Water content should not exceed 6.0%)

(di) n-butanol extract: taking about 3.0g of the product, precisely weighing, placing in a beaker, precisely adding 50ml of water, carrying out ultrasonic treatment for 15 minutes to dissolve, centrifuging, precisely weighing 10ml of supernate, shaking and extracting for 3 times (20 ml, 20ml and 15 ml) by using water saturated n-butyl alcohol, combining n-butyl alcohol extracts, washing for 1 time by using 10ml of water saturated by n-butyl alcohol, taking n-butyl alcohol solution, placing in an evaporating dish dried to constant weight, drying for 3 hours at 105 ℃ after drying on a water bath, cooling for 30 minutes in a drier, and rapidly and precisely weighing to obtain the product. The content of n-butanol in the product should not be less than 12%.

(III) Total Flavonoids

Preparation of control solution rutin control 0.2g dried at 120 deg.C under reduced pressure to constant weight is precisely weighed, placed in 100ml measuring flask, added with 70% ethanol 70ml, placed on water bath to be slightly heated for dissolution, cooled, added with 70% ethanol to scale, and shaken well. Precisely measuring 10ml, placing into a 100-volume flask, adding water to scale, and shaking to obtain the final product (each 1ml contains anhydrous rutin 0.2 mg).

Preparing a standard curve by precisely measuring 1ml, 2ml,3ml, 4ml, 5ml and 6ml of reference substance solution, respectively placing the reference substance solution in a 25ml measuring flask, adding water to 6ml, adding 1ml of 5% sodium nitrite solution, shaking up, placing for 6 minutes, adding 1ml of 10% aluminum nitrate solution, shaking up, placing for 6 minutes, adding 10ml of sodium hydroxide test solution, adding water to the scale, shaking up and placing for 15 minutes; the corresponding solution was blanked. The absorbance was measured at a wavelength of 500nm by ultraviolet-visible spectrophotometry (SOP 20811300), and a standard curve was drawn with the absorbance as the ordinate and the concentration as the abscissa.

Measuring method comprises weighing 0.5g of the product, precisely weighing, placing in 100ml measuring flask, adding 70% ethanol 70ml, placing on water bath, slightly heating, shaking for 30 min, cooling, adding 70% ethanol to scale, shaking, standing for 4 hr, precisely measuring supernatant 1ml, placing in 25ml measuring flask, measuring absorbance according to standard curve preparation method, reading rutin weight in sample solution from standard curve, and calculating.

The content of total flavone in per gram of the product is calculated by anhydrous rutin (C27H 30O 16), and should not be less than 110 mg.

And (IV) measuring luteolin by a high performance liquid chromatography (SOP 20812600) method.

Octadecylsilane chemically bonded silica is used as a filling agent in chromatographic condition and system adaptability tests; methanol-0.2% phosphoric acid solution (40: 60) as mobile phase; the detection wavelength is 350nm, and the number of theoretical plates is not less than 2500 calculated according to luteolin peak.

Preparation of control solution an appropriate amount of luteolin control is precisely weighed, and methanol is added to prepare a solution containing 25 mug per 1ml, so as to obtain the luteolin control solution.

Preparing a test solution, grinding an appropriate amount of the test solution, taking about 2g of fine powder, precisely weighing, placing in a conical flask with a plug, precisely adding 25ml of methanol solution, sealing the plug, weighing, ultrasonically extracting for 30 minutes, cooling, weighing again, supplementing the lost weight with the methanol solution, shaking uniformly, filtering, and adding methanol to dilute to the scale.

The determination method comprises precisely sucking 10ul of each of the reference solution and the sample solution, injecting into liquid chromatograph, and determining.

The content of radix Lamiophlomidis Rotatae in per gram is not less than 0.4mg, calculated as luteolin (C15H 10O 6).

(V) determining shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester by high performance liquid chromatography (SOP 20812600)

Octadecylsilane chemically bonded silica is used as a filler in chromatographic conditions and system applicability tests; acetonitrile is taken as a mobile phase A, water is taken as a mobile phase B, and gradient elution is carried out according to the specification in the following table; the detection wavelength was 235 nm. The number of theoretical plates is not less than 3000 calculated according to shanzhiside methyl ester peak.

。

Preparation of a reference substance solution A proper amount of shanzhiside methyl ester reference substance and an appropriate amount of 8-O-acetyl shanzhiside methyl ester reference substance are precisely weighed and added with methanol to prepare mixed solutions each containing 30 mug per 1ml, so as to obtain the shanzhiside methyl ester reference substance.

Preparation of a test solution: weighing about 0.15g of the product, accurately weighing, placing in a conical flask with a plug, accurately adding 25ml of 70% methanol, sealing the plug, weighing, heating and refluxing for 1 hour, cooling, weighing again, supplementing the lost weight with 70% methanol, shaking up, and filtering. Precisely measuring 2ml of the subsequent filtrate, placing in a 10ml measuring flask, adding methanol to scale, shaking, filtering, and collecting the subsequent filtrate.

And precisely sucking 10 mul of each of the reference solution and the test solution by the measuring method, injecting the solution into a liquid chromatograph, and measuring to obtain the test solution.

The product contains fructus Gardeniae methyl ester (C17H 26O 11) and 8-O-acetyl fructus Gardeniae methyl ester (C19H 28O 12) in a total amount of no less than 12mg per gram.

The test results and stability results are shown in the following table:

pharmacodynamic experiments aiming at the lamiophlomis rotata oral liquid show that: (Experimental animals are from the Experimental animal center of Henan province)

Experiment 1: anti-inflammatory and detumescence effect of lamiophlomis rotata oral liquid

Experiment 1 adopts a xylene-induced mouse auricle swelling method, and observes the inhibition effect of large, medium and small doses of the lamiophlomis rotata oral liquid on mouse auricle swelling, and finds that three dose groups of the lamiophlomis rotata oral liquid have statistical significance (P is less than 0.05) compared with a control group, the large and medium dose groups have obvious inhibition effect on the swelling degree of mouse tissues and are superior to the small dose group, the swelling inhibition rate is enhanced along with the increase of the dose, and the result shows that the lamiophlomis rotata oral liquid has obvious anti-inflammatory and swelling-eliminating effects.

Influence of lamiophlomis rotata oral liquid on mouse auricle swelling caused by dimethylbenzene

Experiment 2: the lamiophlomis rotata oral liquid has the hemostatic effect:

the influence of large, medium and small dosage groups of the lamiophlomis rotata oral liquid on the bleeding time and the plasma thrombin time of a mouse is inspected by a tail breaking method in an experiment, the effect that the lamiophlomis rotata oral liquid of large, medium and small dosage groups can shorten the tail breaking bleeding time of the mouse is found, the hemostatic effect of the large dosage group is extremely obvious, the lamiophlomis rotata oral liquid of large and medium dosage groups can shorten the plasma thrombin time of the mouse, and an obvious dose-effect relationship exists, and the result shows that the lamiophlomis rotata oral liquid has an obvious hemostatic effect.

Influence of lamiophlomis rotata oral liquid on bleeding time and plasma thrombin time of mice

Compared to the saline group: p is less than 0.05

Experiment 3: analgesic effect of lamiophlomis rotata oral liquid

The experiment shows that the mice are treated by respectively using the lamiophlomis rotata oral liquid of large, medium and small dosage groups, the latency period of mouse writhing and the writhing frequency within 15 minutes are observed, the latency period of mouse writhing can be prolonged by the three dosage groups, the writhing frequency is reduced, the latency period of mouse writhing is longer and the writhing frequency is less along with the increase of dosage, and the experimental result shows that the lamiophlomis rotata oral liquid has obvious analgesic effect.

Influence of Lamiophlomis rotata oral liquid on body writhing response of mice caused by acetic acid

Compared to the saline group: p is less than 0.05

The data analysis in experiment 1, experiment 2 and experiment 3 shows that the lamiophlomis rotata oral liquid has obvious effects of diminishing inflammation, diminishing swelling, stopping bleeding and relieving pain. The lamiophlomis rotata oral liquid is orally taken, and the dosage is as follows: one (10 ml/piece) at a time, three times a day, or according to the advice of doctor, the disease condition is reduced; the use condition is as follows: the product is suitable for patients with symptoms of wound pain, hemorrhage, traumatic fracture, sprain of bones and muscles, rheumatic arthralgia, metrorrhagia, dysmenorrhea, gingival swelling and pain, hemorrhage, etc. after surgical operation, and is suitable for diabetic patients because the product does not contain sugar.

Clinical treatment effect experiment:

and (3) judging the curative effect:

the effect is shown: after the medicine is taken for 1 hour, the pain starts to be relieved, the pain stops after 5 to 7 hours, and the pain basically disappears after the medicine is taken for about 4 days continuously. Improvement: after taking the medicine for several hours, the pain and the function are obviously improved.

And (4) invalidation: symptoms and signs were unchanged from those before treatment.

The effective rate of 41 patients and 54 patients with 100 pain patients is 92%, the ineffective rate of 8 patients is 8%, and the results are shown in the table

Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.

Claims (3)

1. A sugar-free lamiophlomis rotata oral liquid preparation is characterized in that each 1000ml of lamiophlomis rotata oral liquid comprises the following components: 400-600 g of lamiophlomis rotata, 20-40 g of xylitol, 1-2 g of potassium sorbate and the balance of purified water.

2. The sugar-free lamiophlomis rotata oral liquid preparation of claim 1, wherein: each 1000ml of the lamiophlomis rotata oral liquid comprises the following components: 500g of lamiophlomis rotata, 30g of xylitol, 2g of potassium sorbate and the balance of purified water.

3. A method for preparing the sugar-free lamiophlomis rotata oral liquid preparation of claim 1, comprising the steps of:

step A: cleaning and selecting the ingredients, namely removing impurities from the lamiophlomis rotata according to the proportion of the ingredients, chopping, and crushing and screening by adopting a screening machine with 10 meshes for later use;

and B: extracting and concentrating, adding 15 times of equivalent water, heating to about 45 ℃, adding the lamiophlomis rotata medicinal material cleaned and selected in the step A, soaking for 2 hours, filtering to obtain a filtrate a and a filter residue b, adding 12 times of equivalent water into the filter residue b, soaking for 2 hours, filtering to obtain a filtrate c, then combining the filtrate a and the filtrate c into a filtrate d, and concentrating the filtrate d into a clear paste with the relative density of 1.10-1.15 under the conditions of the temperature of 65-75 ℃ and the vacuum degree of 0.06-0.08Mpa, wherein the temperature is 70 ℃;

step C, adding 95% ethanol into the clear paste prepared in the step B to enable the ethanol content to reach 60% -80%, standing for 24 hours, filtering, and recovering ethanol from the filtrate until the relative density is 1.20-1.25 and the temperature is 70 ℃;

d, preparing a liquid, namely adding potassium sorbate into the filtrate obtained in the step C, stirring to dissolve the potassium sorbate, adding purified water to adjust the total amount to 1000ml, stirring uniformly, and filtering to obtain a reddish brown clear liquid; then filling 10ml of each bottle, sealing by a gland, and sterilizing in steam at 100 ℃ for 30 minutes.