A traditional Chinese medicine composition, a preparation method and application thereof

Abstract

The present application relates to a kind of traditional Chinese medicine composition and its preparation method, purposes, belong to the field of traditional Chinese medicine.The traditional Chinese medicine composition is prepared from radix paeoniae alba, salvia miltiorrhiza, caulis et ramus youngia, rhizoma sinodendri, liquorice, cornus officinalis, chaenomelis fruit and gentiana macrophylla 8 raw medicinal materials.The composition of the present application is assisted by compatibility of several drugs, synergistic effect, can dredge meridian, tonify liver and kidney, invigorate spleen and stomach, stop arthralgia, suitable for the treatment of increased muscle tension.The results of pharmacodynamic experiment show that the composition of the present application can significantly improve the symptoms of increased muscle tension caused by post-stroke sequelae, spinal cord injury and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition and a preparation method and use thereof, and especially relates to a traditional Chinese medicine composition for treating hypertonia and a preparation method thereof. BACKGROUND

[0002] Hypertonia is a common complication accompanying the damage of upper motor neurons, and can be caused by the damage of central nervous system due to various reasons, and can be seen in stroke, Parkinson's disease, brain trauma, spinal cord injury, etc., especially after stroke, and is mainly manifested as the hypertonia of muscle groups and the abnormal muscle movement coordination caused thereby. Hypertonia is a major problem for the rehabilitation of the limbs of patients, and seriously affects the self-care ability and quality of life of patients.

[0003] In traditional Chinese medicine, hypertonia is named as "spasticity" or "limb rigidity", and is classified into the collateral syndrome category of stroke, and belongs to the "convulsion syndrome" category of traditional Chinese medicine. The understanding of limb spasticity in traditional Chinese medicine is different from "meridian disease" and "visceral disease", and the pathogenesis is also different from "yin-yang imbalance" and "excess or deficiency". Traditional Chinese medicine believes that muscle tension is equivalent to fascia in traditional Chinese medicine, and the flexion and extension of muscles and joints and the movement of limbs are related to meridians, and the symptoms of hypertonia are equivalent to the traction and rigidity of meridians, which belong to the "tendon injury" and "arthralgia syndrome" category, and are related to yin-yang imbalance and meridian deficiency. The unsmooth meridians, the imbalance of blood circulation, the deficiency of meridians, the imbalance of the function of "binding bones and benefiting joints", and the contraction of meridians are the main pathogenesis of spasticity.

[0004] The research and treatment of hypertonia include drugs, acupuncture, surgery, electrical stimulation, etc. Modern medicine believes that the damage of pyramidal tract or extrapyramidal system can cause hypertonia, and the current research of western medicine on hypertonia after stroke mainly focuses on molecular biology, such as the research on neuropeptide P substance. In the aspect of internal medicine treatment, there are central antispastic drugs and peripheral antispastic drugs, such as baclofen, botulinum toxin type A, myonal, dantrolene, tizanidine, phenytoin sodium, etc. However, the inhibitory effect of such drugs on spasticity is temporary, and needs to be used multiple times, which can have certain adverse effects on the patient's spirit or gastrointestinal system. In the aspect of surgical treatment, posterior fiber section of upper cervical sympathetic ganglion can be performed to reduce the vasoconstriction reaction caused by hypoxia, and selectively improve the oxygen supply of the cortical area in the case of increased oxygen uptake. However, this method can cause certain defects in the regulation of the body, and its long-term effect needs to be observed and evaluated. In the aspect of physical rehabilitation treatment, brain reflex therapy instrument, Huftschmidt electrical therapy stimulation of spastic muscles and antagonistic muscles, and early rehabilitation treatment, etc. are used, although the effect is good, but the treatment course is long and the effect is slow. Therefore, it is an urgent field to be developed to explore the treatment method of hypertonia from the aspect of traditional Chinese medicine, and to fully play the great role of traditional Chinese medicine. Summary of the Invention

[0005] In view of the shortcomings of the existing Western medicine treatment of increased muscle tone, the purpose of the present invention is to provide a traditional Chinese medicine composition for treating increased muscle tone.

[0006] The technical solutions of the present invention are as follows:

[0007] A traditional Chinese medicine composition is prepared from eight raw medicinal materials: white peony root, salvia miltiorrhiza, millettia reticulata, herba striatae, roasted liquorice, cornus fruit, papaya, and gentiana macrophylla.

[0008] Preferably, the Chinese medicine composition is made from the following Chinese medicine components:

[0009] 40-60 parts by weight of white peony root, 5-25 parts by weight of salvia miltiorrhiza, 5-25 parts by weight of Millettia reticulata

[0010] 5-25 parts by weight of Herba Lycopodii Herba 40-60 parts by weight of Radix Glycyrrhizae Preparata 5-25 parts by weight of Fructus Corni

[0011] 5-25 parts by weight of papaya 5-25 parts by weight of gentiana macrophylla

[0012] Preferably, the Chinese medicine composition is made from the following Chinese medicine components:

[0013] 45-55 parts by weight of white peony root, 10-20 parts by weight of salvia miltiorrhiza, 10-20 parts by weight of Spatholobus suberectus

[0014] 10-20 parts by weight of Herba Lycopodii Herba 45-55 parts by weight of Radix Glycyrrhizae Preparata 10-20 parts by weight of Fructus Corni

[0015] 10-20 parts by weight of papaya 10-20 parts by weight of gentiana macrophylla

[0016] Further preferably, the Chinese medicine composition is made from the following Chinese medicine components:

[0017] 50 parts by weight of white peony root, 15 parts by weight of salvia miltiorrhiza, 15 parts by weight of Spatholobus suberectus

[0018] 15 parts by weight of Herba Lycopodii Herba 50 parts by weight of Radix Glycyrrhizae Preparata 15 parts by weight of Fructus Corni

[0019] 15 parts by weight of papaya and 15 parts by weight of gentiana macrophylla.

[0020] In the formula, white peony root is sour in taste and enters the liver, nourishing blood and restraining yin, softening the liver and relieving pain, and suppressing liver yang, and is the main medicine; roasted licorice root is sweet in taste and enters the spleen and stomach meridians, nourishing yin and nourishing the stomach; cornus fruit invigorates qi and strengthens the spleen, harmonizes the middle and promotes yang, nourishes the liver and kidneys, and astringes essence and stops sweating; salvia miltiorrhiza, smilax glabra, papaya, and millettia reticulata, promote blood circulation and remove blood stasis, promote menstruation and relieve pain, cool blood and eliminate carbuncles, dispel wind and dampness, relax muscles and activate collaterals, harmonize the stomach and eliminate dampness, and are the minister medicines; gentiana macrophylla dispels rheumatism, clears damp-heat, stops arthralgia and pain, and reduces deficiency fever, and is the adjuvant medicine.

[0021] The above-mentioned eight Chinese medicines, such as white peony root, mutually assist and match, synergistically enhance, can dredge meridians, tonify liver and kidney, invigorate spleen and stomach, stop arthralgia, and are suitable for the treatment of increased muscle tension, and have exact curative effect on the symptoms of increased muscle tension caused by various reasons.

[0022] Another object of the present application is to provide a Chinese medicine oral preparation containing the above-mentioned Chinese medicine composition and a preparation method thereof, wherein the Chinese medicine oral preparation is one of oral liquid, granules, capsules, tablets, pills, and microcapsules.

[0023] The preparation method of the Chinese medicine oral preparation comprises the following steps:

[0024] (1) Take 8 kinds of raw medicinal materials of white peony root, salvia miltiorrhiza, caesalpinia japonica, smilax riparia, honeyed licorice, dogwood fruit, papaya, and gentiana, clean and select, respectively, coarsely crush, and obtain raw medicinal material coarse granules for standby;

[0025] (2) Take the raw medicinal material coarse granules in step (1), mix, add 6-10 times amount of water, decoct for 2 times, each time for 2-3 hours, filter the decocting liquid, reduce pressure and concentrate, obtain extract, and standby;

[0026] (3) Add ethanol to the extract obtained in step (2) to make the alcohol content reach 60%-70%, stand and cold sediment, filter, recover ethanol from the filtrate, concentrate, obtain extract, and standby;

[0027] (4) Take the extract in step (3), add pharmaceutically acceptable excipients according to the conventional process to prepare oral drug preparation.

[0028] Preferably, the extract in step (2) is reduced pressure concentrated to relative density of 1.12-1.18 at 50-60℃.

[0029] Preferably, the extract in step (3) is reduced pressure concentrated to relative density of 1.25-1.30 at 50-60℃.

[0030] The acceptable excipients include one or several of fillers, lubricants, preservatives, flavoring agents, disintegrants, binders, colorants, and dispersants.

[0031] The pharmaceutically acceptable excipients include but are not limited to lactose, starch, dextrin, sugar powder, magnesium stearate, maltose, lemon water, tartaric acid, sodium hydroxide, aspartame, stevioside, cyclamate, protein sugar, potassium acesulfame, aspartame, sucralose, sodium benzoate, etc.

[0032] In one embodiment, the Chinese medicine oral preparation is granules, and the preparation method of the granules comprises the following steps:

[0033] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0034] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, decocting them twice, adding 8 times the amount of water for the first time and decocting them for 2 hours, and adding 6 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and setting it aside;

[0035] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%, standing and cooling for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.30 at 50-60°C, and setting aside;

[0036] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.09 MPa to 0.10 MPa and 60° C., grind into fine powder, sieve, add the formulated amount of sucrose powder, dextrin, and mannitol (weight ratio of 3:1:1), mix well, granulate, dry, and shape the particles to obtain granules.

[0037] In another embodiment, the oral formulation is a micropill, and the preparation method of the micropill comprises the following steps:

[0038] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0039] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 10 times the amount of water for the first time and decocting them for 3 hours, and adding 6 times the amount of water for the second time and decocting them for 3 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and setting it aside;

[0040] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.26 at 50-60°C, and setting aside;

[0041] (4) The extract of step (3) was taken, and belt vacuum dried at a vacuum degree of -0.09 MPa to 0.10 MPa and 60° C., crushed into a fine powder, sieved, added with microcrystalline cellulose, chitosan, dextrin, micropowder silica gel, and dextrin, and fully mixed. A 30% ethanol solution with a concentration of 40% (by weight) of the prescription amount was added as a wetting agent and kneaded continuously to form a soft material, which was extruded into strips through a sieve plate with an aperture of 0.9 mm in an extruder; a spheronizer was turned on, a speed of 1100 rpm was selected, and the strips were placed in the spheronizer for 6 minutes until the particles were rolled into pellets, and the semi-finished pellets were taken out and dried at 65° C., and sieved to obtain pellets with a mesh size of 20-30.

[0042] The present invention provides use of the traditional Chinese medicine composition in preparing a medicament for treating increased muscle tone, and the composition has a definite therapeutic effect on the symptoms of increased muscle tone caused by sequelae of stroke, spinal cord injury and the like.

[0043] The traditional Chinese medicine composition described in this invention is made from eight raw medicinal materials: white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla. It can dredge meridians, nourish the liver and kidneys, strengthen the spleen and stomach, and relieve pain. It is suitable for treating hypertonia. Animal experiments have shown that the composition can significantly improve symptoms of hypertonia caused by post-stroke sequelae, spinal cord injury, and other causes.

[0044] To verify the efficacy of the Chinese herbal composition of the present invention in treating hypertonia, the inventors conducted pharmacodynamic studies. It should be noted that the drugs selected for the pharmacodynamic studies are those obtained from a representative formulation and preparation method of the present invention. Due to space limitations, the tests and results of other drugs obtained from formulations and preparation methods encompassed by the present invention are not exhaustively listed here.

[0045] Experimental Example 1: Effects of suture-induced post-stroke spastic muscle tension in rats

[0046] 1 Experimental Materials

[0047] 1.1 Experimental Animals

[0048] Eighty-four SPF-grade male Sprague-Dawley rats, 8 weeks old, weighing 180-220 g, were provided by Lunan Pharmaceutical Group Co., Ltd. (Laboratory Animal Certificate No. SYXK(Lu)2018-0008). The animals were housed in separate cages in a dedicated laboratory under natural light, with free access to food and water. The animals were fed a pelleted diet and maintained at room temperature at 20-25°C and relative humidity at 45%-65%. Experiments were conducted after one week of adaptive feeding.

[0049] 1.2 Instruments, reagents and drugs

[0050] An electronic balance (YB502, Shanghai Precision Instrument Co., Ltd.), an electronic analytical balance (AG285, Mettler Toledo), a physiological recorder (BL-420S, Chengdu Taimeng Software Co., Ltd.), disposable sterile needles (0.25 mm × 13 mm long, Suzhou Medical Supplies Factory Co., Ltd.), and a middle cerebral artery occlusion (MCAO) suture plug (503356PK5Re, Tianjin Minxue Technology Co., Ltd.) were used. The test drug was an oral liquid sample prepared according to the formulation and preparation method of Example 1; the drug required for the peony and licorice group was a granule sample prepared according to the formulation and preparation method of Comparative Example 1; the positive control drug was baclofen tablets (specification: 10 mg / tablet, national medicine standard H19980103), a product of Ningbo Tianheng Pharmaceutical Co., Ltd., Fu'an Pharmaceutical Group.

[0051] 2 Experimental methods

[0052] 2.1 Modeling method

[0053] 84 rats after adaptive feeding were randomly divided into 7 groups, namely sham operation group, model group, positive drug group, peony and licorice group, and experimental group (high dose, medium dose and low dose), with 12 rats in each group. Except for the sham operation group, the other groups were prepared with right cerebral MCAO limb spasticity model. Before surgery, the rats were not allowed to drink water for 24 hours and not allowed to eat for 12 hours; the rats were fixed in supine position on the experimental animal dissection table and anesthetized by intraperitoneal injection of 2% sodium pentobarbital (0.2mL / 100g). The neck was prepared and disinfected with 75% alcohol. Sterile surgical cloth was laid. A longitudinal incision of about 1.5cm was made along the middle right side of the neck. The common carotid artery was separated from the internal and external carotid arteries by blunt separation. The proximal end (near the bifurcation) was ligated with No. 5 thread. After ligation, the internal carotid artery was clamped with a micro artery clamp. An incision 5 mm from the bifurcation bulge was made to insert the MCAO suture plug, and the arterial clamp was loosened to a depth of about 18-20 mm. The insertion of the suture was stopped when a slight resistance was felt, and the proximal end of the ICA and the suture plug were ligated together. After the model was completed, the incision was sutured layer by layer, covered with sterile gauze, and placed back in the breeding cage to wait for the rat to wake up. After the model was established, gentamicin was injected intraperitoneally for 3 consecutive days to prevent postoperative infection; furosemide (0.1 mg / kg) was injected after the operation to prevent cerebral edema, and a heating lamp was used to ensure that the rectal temperature of the rat was around 37°C after the operation.

[0054] 2.2 Grouped Dosing

[0055] Ten rats in each group were treated with the corresponding drug. The clinical dose of the test drug was 3.74 g crude drug / kg. The doses for the high-, medium-, and low-dose groups were 7.48 g crude drug / kg, 3.74 g crude drug / kg, and 1.87 g crude drug / kg, respectively, equivalent to 2 times, 1 / 2 times, and 1 / 2 times the commonly used human clinical dose. The positive control group received 1.35 mg / kg of baclofen tablets, equivalent to the commonly used human clinical dose. For administration, the test drug and positive control were prepared into equal volumes of solutions with varying concentrations. On the first day after surgery, each group received an oral gavage of 2 mL / 100 g. The normal and model control groups received an equal volume of distilled water, once daily in the morning and evening, for two consecutive weeks.

[0056] 2.3 Evaluation indicators

[0057] (1) Evaluation of the degree of neurological deficit: The Bederson scoring method was used to evaluate the degree of neurological deficit in rats 2 weeks after modeling. The scores were divided into 0 points (no neurological deficit), 1 point (any flexion component of the forelimbs, i.e., positive tail-hanging test, without other abnormalities), 2 points (decreased resistance to lateral thrust, i.e., positive lateral thrust test, accompanied by flexion of the forelimbs, and no circling behavior), and 3 points (same behavior as in point 2, accompanied by spontaneous rotation and circling toward the paralyzed side during free activity).

[0058] (2) Muscle tension measurement: Two weeks after modeling, the muscle tension of rats was evaluated using electrophysiological recording (BL-420S biofunctional experimental system). Rats were lightly anesthetized by intraperitoneal injection of 10% chloral hydrate (3.5 mL / kg). One end of the electric stimulation needle was inserted into the quadriceps brachii muscle of the rat's left hind limb, and the other end was inserted into the rat's tail. A low-compliance cotton thread was tied to the lower end of the rat's left hind limb and connected to the BL-420S biofunctional experimental system via a tension sensor. A 0.5 g afterload was applied, and the quadriceps femoris of the rat was stimulated at regular intervals with a stimulation dose of 3 mA and a stimulation time of 30 s. The electrical signal generated by the electrical stimulation of the quadriceps femoris of the left hind limb was recorded by the biofunctional experimental system, which indirectly reflects the muscle tension of the rat and is used to indicate the degree of limb spasticity in the rat.

[0059] 2.4 Statistical methods

[0060] SPSS 20.0 statistical software was used for analysis and processing. Experimental data were expressed as “mean ± standard deviation”. The differences among the groups were compared using one-way analysis of variance, and P < 0.05 indicated statistical significance.

[0061] 3 Experimental results

[0062] The experimental results are shown in Table 1. As shown in Table 1, after 2 weeks of treatment, the paeony licorice group and different dose test groups improved the degree of neurological impairment in rats to varying degrees, among which the high dose test group and the medium dose test group were better than the paeony licorice group, and the difference was statistically significant (P<0.05); the positive drug baclofen group had no significant improvement in the neurological impairment of rats. After 2 weeks of treatment, the muscle tension of rats in the positive drug group, the paeony licorice group and the different dose test groups was reduced to varying degrees, among which the high dose test group and the medium dose test group were better than the paeony licorice group, and the difference was statistically significant (P<0.05).

[0063] Table 1 Comparison of the degree of neurological impairment of rats in each group

[0064]

[0065] Note: Compared with the model group: * P<0.05; compared with the paeony licorice group: # P<0.05.

[0066] Effect of test example 2 on the spastic paralysis model after spinal cord injury (SCI) in rats

[0067] 1. Experimental materials

[0068] 1.1 Experimental animals

[0069] 84 SPF level SD rats, male, 8 weeks old, body weight 180-220 g, provided by Lunan Pharmaceutical Group Co., Ltd., experimental animal qualification certificate No. SYXK(Lu)2018-0008. Animals were housed in a special laboratory, natural light, free access to food and water, pellet feed, room temperature controlled at 20-25℃, relative humidity controlled at 45%-65%, and acclimated for 1 week before testing.

[0070] 1.2 Instruments, reagents and drugs

[0071] Electronic balance (YB502 type, Shanghai Precision Instruments and Meters Co., Ltd.), electronic analytical balance (AG285 type, Mettler Toledo), physiological recorder (BL-420S type, Chengdu Tailian Software Co., Ltd.); enzyme-linked immunosorbent assay (BIO-RAD, USA BIO Company), GABA (gamma-aminobutyric acid), Gly (glycine) kit (USA Thermo Fisher Company). The test drug is a granule sample prepared according to the formula and preparation method in Example 3; the paeony licorice group requires a granule sample prepared according to the formula and preparation method in Comparative Example 1; the positive control drug is baclofen tablets (specification: 10 mg / tablet, GMP code H19980103), a product of Fuan Pharmaceutical Group Ningbo Tianheng Pharmaceutical Co., Ltd.

[0072] 2 Experimental methods

[0073] 2.1 Modeling method

[0074] 84 rats were randomly divided into 7 groups after adaptive feeding, namely sham operation group, model group, positive group, peony root and liquorice root group, and experimental group (high dose group, medium dose group and low dose group), with 12 rats in each group. Except for the sham operation group, the spasticity model after spinal cord injury was prepared in all other groups. The rats were fixed on the experimental animal dissection table and anesthetized by intraperitoneal injection of 2% sodium pentobarbital (0.2mL / 100g). The skin was prepared and incised to expose the dura mater sac of the T9-T11 segment. The dura mater scalp was gently pushed to the left with the median vein. The dura mater sac of the T9 segment was longitudinally incised under the median vein. Colorless and transparent cerebrospinal fluid was observed to flow out. The front of the dura mater was pressed against the anterior edge of the spinal canal and the blade was rotated perpendicular to the longitudinal incision. The blade was pointed to the right side and the right spinal cord was quickly transected. At the same time, the right hind limb of the rat was observed to retract spasmodically, the tail of the rat quickly deviated to the left, and a small amount of blood oozed out of the spinal canal. The wound was sutured in sequence. In the sham operation group, only the dura mater was exposed. Postoperative care including penicillin injection and artificial urination.

[0075] 2.2 Grouped Dosing

[0076] Ten rats with successful modeling were selected from each group and received the corresponding drug treatment. The clinical dose of the test drug was 3.74 g crude drug / kg. The doses for the high-, medium-, and low-dose groups were 7.48 g crude drug / kg, 3.74 g crude drug / kg, and 1.87 g crude drug / kg, respectively, which are equivalent to 2 times, 1 / 2 times, and 1 / 2 times the commonly used human clinical dose. The positive control group received 1.35 mg / kg of baclofen tablets, which is 1 / 2 times the commonly used human clinical dose. For administration, the test drug and positive control drug were prepared into equal volumes of solutions with varying concentrations. On the first day after surgery, each group received an oral gavage of 2 mL / 100 g. The normal control and model control groups received an equal volume of distilled water, once daily in the morning and evening for two consecutive weeks.

[0077] 2.3 Evaluation indicators

[0078] (1) Muscle tension measurement: The muscle tension of rats was evaluated using electrophysiological recording (BL-420S biofunction experimental system).

[0079] (2) GABA and Gly levels: After treatment, approximately 1.0 cm of spinal cord tissue was removed from the original surgical approach, weighed, and added to an equal volume of prepared PBS at a mass-to-volume ratio of 1:1. The homogenate was then added to a 9x PBS solution, shaken, and centrifuged at 4000 rpm for 10 min. The supernatant was collected. GABA and Gly levels in the spinal cord tissue of each group were measured using a kit.

[0080] 2.4 Statistical methods

[0081] SPSS 20.0 statistical software was used for analysis and processing. The experimental data were expressed as “mean ± standard deviation ( )”, and one-way analysis of variance was used to compare the differences among the groups. P < 0.05 indicated statistical significance.

[0082] 3 Experimental results

[0083] 3.1 Effects of Chinese herbal medicine composition on rat muscle tension

[0084] The experimental results are shown in Table 2. After 2 weeks of administration, the muscle tension evaluation of the positive drug group, the peony and licorice group, and each experimental group was significantly reduced, among which the high-dose treatment group and the medium-dose treatment group had better effects than the peony and licorice group (P < 0.05).

[0085] Table 2 Comparison of muscle tension evaluation in rats of each group

[0086]

[0087] Note: Compared with the model group: * P<0.05; compared with the peony and licorice group: # P<0.05.

[0088] 3.2 Effects of the Chinese herbal medicine composition on the levels of inhibitory transmitters γ-aminobutyric acid (GABA) and glycine (Gly) in the rat spinal cord

[0089] The experimental results are shown in Table 3. The levels of inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine (Gly) in the spinal cord of the positive drug group, the peony and licorice group and each experimental group increased to varying degrees; among them, the GABA and Gly levels in the medium and high dose groups of the experiment were statistically different from those in the peony and licorice group (P < 0.05).

[0090] Table 3 Comparison of GABA and Gly levels in rats of each group

[0091]

[0092] Note: Compared with the model group: * P<0.05; compared with the peony and licorice group: # P<0.05.

[0093] The above experimental results show that the composition of the present invention can significantly improve the symptoms of increased muscle tone caused by sequelae of stroke, spinal cord injury, etc. DETAILED DESCRIPTION

[0094] In order to enable those skilled in the art to fully understand the present invention, the present invention is further described below through specific examples. However, those skilled in the art should be aware that the examples of the present invention do not limit the present invention in any way.

[0095] Example 1 Preparation of oral liquid

[0096]

[0097] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0098] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 10 times the amount of water for the first time and decocting them for 3 hours, and adding 8 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and setting it aside;

[0099] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 65%, standing and cooling for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.25 at 50-60°C, and setting aside;

[0100] (4) Take the extract prepared in step (3), add purified water to the total amount, add sodium benzoate, filter until the clarity is qualified, then fill, sterilize, and package to obtain the oral solution.

[0101] Example 2 Preparation of Oral Liquid

[0102]

[0103] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0104] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, decocting them twice, adding 8 times the amount of water for the first time and decocting them for 2 hours, and adding 8 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.14 at 50-60°C, and setting it aside;

[0105] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 70%, standing and cooling for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.28 at 50-60°C, and setting aside;

[0106] (4) Take the extract prepared in step (3), add purified water to the total amount, add sodium benzoate, filter until the clarity is qualified, then fill, sterilize, and package to obtain the oral solution.

[0107] Example 3 Preparation of granules

[0108]

[0109] (1) Take 8 kinds of raw medicinal materials of white peony root, salvia miltiorrhiza, caesalpinia, sinomenium, licorice, dogwood fruit, papaya and gentiana, clean and select, respectively coarse crush, get raw medicinal material coarse particles, for future use;

[0110] (2) Take the raw medicinal material coarse particles of step (1), mix evenly, decoct twice, the first time add 8 times the amount of water, decoct 2h, the second time add 6 times the amount of water, decoct 2h, filter the decocting liquid, reduce pressure concentration to 50-60℃ when the relative density of the extract is 1.12, for future use;

[0111] (3) The extract obtained in step (2) is added with ethanol to make the alcohol content reach 60%, and then placed and cold settled for 24h, filtered, and the filtrate is recovered with ethanol and concentrated to 50-60℃ when the relative density of the extract is 1.30, for future use;

[0112] (4) Take the extract of step (3), under the conditions of vacuum degree-0.09MPa--0.10Mpa, 60℃, carry out belt vacuum drying, crush into fine powder, sieve, add the formula amount of sucrose powder, dextrin, mannitol (weight ratio 3:1:1), mix evenly, granulate, dry, and whole grain, to obtain granules.

[0113] Preparation of granules in example 4

[0114]

[0115] (1) Take 8 kinds of raw medicinal materials of white peony root, salvia miltiorrhiza, caesalpinia, sinomenium, licorice, dogwood fruit, papaya and gentiana, clean and select, respectively coarse crush, get raw medicinal material coarse particles, for future use;

[0116] (2) Take the raw medicinal material coarse particles of step (1), mix evenly, decoct twice, the first time add 10 times the amount of water, decoct 2.5h, the second time add 6 times the amount of water, decoct 2.5h, filter the decocting liquid, reduce pressure concentration to 50-60℃ when the relative density of the extract is 1.18, for future use;

[0117] (3) The extract obtained in step (2) is added with ethanol to make the alcohol content reach 60%, and then placed and cold settled for 48h, filtered, and the filtrate is recovered with ethanol and concentrated to 50-60℃ when the relative density of the extract is 1.25, for future use;

[0118] (4) Take the extract of step (3), under the conditions of vacuum degree-0.09MPa--0.10Mpa, 60℃, carry out belt vacuum drying, crush into fine powder, sieve, add the formula amount of starch, microcrystalline cellulose (weight ratio 5:2), mix evenly, granulate, dry, and whole grain, to obtain granules.

[0119] Preparation of granules in example 5

[0120]

[0121] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0122] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 10 times the amount of water for the first time and decocting them for 3 hours, and adding 10 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.15 at 50-60°C, and setting it aside;

[0123] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 65%, standing and cooling for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.30 at 50-60°C, and setting aside;

[0124] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.09 MPa to 0.10 MPa and 60°C, grind into fine powder, sieve, mix with dextrin in a ratio of 1:2, add 90% ethanol to make a soft material, make granules, dry, and granulate to obtain granules.

[0125] Example 6 Preparation of Tablets

[0126]

[0127] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0128] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, decocting them twice, adding 8 times the amount of water for the first time and decocting them for 2 hours, and adding 7 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.16 at 50-60°C, and setting it aside;

[0129] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.28 at 50-60°C, and setting aside;

[0130] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.09 MPa to 0.10 MPa and 60°C, grind into fine powder, sieve, add the formulated amount of microcrystalline cellulose and hydroxypropyl cellulose (weight ratio 4:3), mix well, granulate, dry, add 0.2% magnesium stearate and 0.1% talc, mix well, compress into tablets, and film-coat to obtain tablets.

[0131] Example 7 Preparation of Oral Liquid

[0132]

[0133] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0134] (2) Take the coarse granules of the raw medicinal materials in step (1), mix them evenly, and decoct them twice. The first time, add 8 times the amount of water and decoct them for 2.5 hours. The second time, add 6 times the amount of water and decoct them for 2 hours. The decoction is filtered and concentrated under reduced pressure to an extract with a relative density of 1.18 at 50-60°C, and set aside.

[0135] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 70%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.27 at 50-60°C, and setting aside;

[0136] (4) Take the extract prepared in step (3), add purified water to the total amount, filter until the clarity is qualified, then fill, sterilize, and package to obtain the oral solution.

[0137] Example 8 Preparation of Micropellets

[0138]

[0139] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0140] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 10 times the amount of water for the first time and decocting them for 3 hours, and adding 6 times the amount of water for the second time and decocting them for 3 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and setting it aside;

[0141] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.26 at 50-60°C, and setting aside;

[0142] (4) The extract of step (3) was taken, and belt vacuum dried at a vacuum degree of -0.09 MPa to 0.10 MPa and 60° C., crushed into a fine powder, sieved, added with microcrystalline cellulose, chitosan, dextrin, micropowder silica gel, and dextrin, and fully mixed. A 30% ethanol solution with a concentration of 40% (by weight) of the prescription amount was added as a wetting agent and kneaded continuously to form a soft material, which was extruded into strips through a sieve plate with an aperture of 0.9 mm in an extruder; a spheronizer was turned on, a speed of 1100 rpm was selected, and the strips were placed in the spheronizer for 6 minutes until the particles were rolled into pellets, and the semi-finished pellets were taken out and dried at 65° C., and sieved to obtain pellets with a mesh size of 20-30.

[0143] Example 9 Preparation of Tablets

[0144]

[0145] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0146] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 6 times the amount of water for the first time and decocting them for 3 hours, and adding 6 times the amount of water for the second time and decocting them for 2.5 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.15 at 50-60°C, and setting it aside;

[0147] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 70%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.23 at 50-60°C, and setting aside;

[0148] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.09 MPa to 0.10 MPa and 60°C, grind into fine powder, sieve, add the formulated amount of starch, dextrin and sucrose (weight ratio of 5:1:2), mix well, granulate, dry at low temperature, shape the granules, add 0.35% magnesium stearate, mix well, compress into tablets, and film-coat to obtain tablets.

[0149] Example 10 Preparation of capsules

[0150]

[0151] (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use;

[0152] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, decocting them twice, adding 7 times the amount of water for the first time and decocting them for 3 hours, and adding 7 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.18 at 50-60°C, and setting it aside;

[0153] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 65%, standing and cooling for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.28 at 50-60°C, and setting aside;

[0154] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.09 MPa to 0.10 MPa and 60° C., grind into fine powder, sieve, add the formulated amount of starch and microcrystalline cellulose (weight ratio 7:2), mix well, granulate, dry, granulate, fill, polish in a grinder, remove damaged capsules, and obtain capsules.

[0155] Comparative Example 1 Preparation of Peony and Licorice Granules

[0156] White Peony Root 1.5kg, Licorice Root 0.5kg

[0157] (1) Weigh two raw medicinal materials, white peony root and liquorice root, clean and coarsely chop them to obtain coarse raw medicinal material granules, and set aside;

[0158] (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, and decocting them twice, adding 10 times the amount of water for the first time and decocting them for 2 hours, and adding 10 times the amount of water for the second time and decocting them for 2 hours, filtering the decoction, and concentrating it under reduced pressure to an extract with a relative density of 1.12 at 50-60°C, and setting it aside;

[0159] (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%, standing and cooling for 24 hours, filtering, recovering ethanol from the filtrate, and concentrating to an extract with a relative density of 1.30 at 50-60°C, and setting aside;

[0160] (4) Take the extract prepared in step (3), perform belt vacuum drying at a vacuum degree of -0.08 MPa and 70°C, grind into a fine powder, sieve, add twice the amount of mixed excipients (dextrin and lactose mixed in a ratio of 1:1), add 75% ethanol to prepare a soft material, sieve, granulate, dry, and granulate to obtain granules.

Claims

1. A Chinese medicine composition, characterized in that Made from the following Chinese medicinal ingredients:

2. The Chinese medicine composition according to claim 1, characterized in that Made from the following Chinese medicinal ingredients:

3. The Chinese medicine composition according to claim 1, characterized in that Made from the following Chinese medicinal ingredients:

4. A Chinese medicine oral preparation, characterized in that: A Chinese medicine composition comprising the method according to any one of claims 1 to 3.

5. The oral Chinese medicine preparation according to claim 4, characterized in that: The Chinese medicine oral preparation is one of oral liquid, granules, capsules, tablets, pills and microcapsules.

6. The method for preparing the oral Chinese medicine preparation according to claim 5, characterized in that: The following steps are involved: (1) Weigh eight raw medicinal materials, including white peony root, salvia miltiorrhiza, millettia reticulata, herba schizonepetae, licorice root, cornus fruit, papaya, and gentiana macrophylla, clean and chop them separately to obtain coarse raw medicinal material granules for later use; (2) taking the crude granules of the raw medicinal materials in step (1), mixing them evenly, adding 6-10 times the amount of water and boiling them twice, each time for 2-3 hours, filtering the decoction, and concentrating under reduced pressure to obtain an extract for later use; (3) adding ethanol to the extract obtained in step (2) to make the alcohol content reach 60%-70%, standing and cooling, filtering, recovering ethanol from the filtrate, concentrating, and obtaining an extract for later use; (4) Take the extract prepared in step (3) and add pharmaceutically acceptable excipients according to conventional processes to prepare an oral pharmaceutical preparation.

7. The preparation method according to claim 6, characterized in that The step (2) is concentrated under reduced pressure to obtain an extract having a relative density of 1.12-1.18 at 50-60° C.

8. The preparation method according to claim 6, characterized in that Step (3) is concentrated under reduced pressure to obtain an extract having a relative density of 1.25-1.30 at 50-60° C.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating hypertonia.

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