CN112023006A

CN112023006A - A topical Chinese medicinal composition for treating rheumatism, and its preparation method and application

Info

Publication number: CN112023006A
Application number: CN201911095019.8A
Authority: CN
Inventors: 崔磊
Original assignee: Qigihar Xianghe Traditional Chinese Medicine Instrument Co ltd
Current assignee: Qigihar Xianghe Traditional Chinese Medicine Instrument Co ltd
Priority date: 2019-11-11
Filing date: 2019-11-11
Publication date: 2020-12-04
Anticipated expiration: 2039-11-11
Also published as: CN112023006B

Abstract

The invention discloses an external traditional Chinese medicine composition for treating rheumatism as well as a preparation method and application thereof. The invention takes radix angelicae pubescentis which is pungent, bitter, slightly warm and can dispel wind-cold-damp evil as a monarch drug, and cassia twig which can induce sweat, release muscles and warm and dredge channels and collaterals is used as an auxiliary drug. The traditional Chinese medicine is prepared by combining folium artemisiae argyi and rhizoma zingiberis which warm the channels and dispel cold to relieve pain, and matching with safflower and rhizoma ligustici wallichii which have the functions of promoting blood circulation and clearing the channels and collaterals, dispersing exterior cold and dispelling wind-damp, notopterygium root which has the functions of dispelling wind-damp, large-leaved gentian which has the functions of expelling wind-damp, dredging the collaterals and relieving pain, angelica which has the functions of enriching the blood and promoting blood circulation, Chinese herbaceous peony which has the functions of nourishing blood and astringing yin, suppressing liver yang and softening liver and relieving pain, and Chinese taxillus which has the functions of tonifying liver and kidney, strengthening bones and muscles and eliminating wind-damp, and a formula which has the functions of promoting blood circulation and nourishing blood, dispelling wind and removing dampness, clearing the channels and activating collaterals, warming the channels and dispelling cold and strengthening the bones.

Description

A topical Chinese medicinal composition for treating rheumatism, and its preparation method and application

Technical Field

The invention relates to an external traditional Chinese medicine composition for treating rheumatism, a preparation method and application thereof, and gel paste prepared from the external traditional Chinese medicine composition. The invention belongs to the technical field of traditional Chinese medicines.

Background

Rheumatism belongs to the category of arthralgia of traditional Chinese medicine, so the traditional Chinese medicine is called as wind-cold-dampness arthralgia, is mainly chronic and systemic manifestations, can affect limbs, joints, muscles, bones and muscles or affect viscera, and is clinically characterized by pain, numbness, soreness, heaviness, swelling, stiffness, deformation, dysfunction and the like. After the disease occurs, the adverse effects are brought to the life, work, sleep quality and the like of the patient. For the first time, the name of rheumatism recorded in the book of jin Kui Yao L ü e records that the profuse pulse is unsmooth, short breath, spontaneous sweating, pain in the joints and not flexible, which are caused by drinking sweat and wind, the lesser yin pulse is superficial and weak, weak is insufficient in blood, superficial is wind, and wind and blood are mutually in conflict, namely pain is caused by dragging.

The traditional Chinese medicine considers that the aetiology of wind-cold-dampness arthralgia is divided into two aspects of external cause and internal cause, as described in Su Wen Bi syndrome: wind-cold-dampness leading to qi deficiency is combined to produce arthralgia. The external causes are mainly related to wind, cold and dampness, while the internal causes are mainly due to deficiency of the vital qi, and the internal causes are combined with the external causes to cause arthralgia. It is seen that the pathogenesis of this disease is wind, cold and dampness blocking meridians, tendons and bones, leaving joints, obstructed nutrient and defensive qi, and obstructed qi and blood circulation. The patients with mild disease feel sore, painful and itchy only in certain limbs, joints and other places, and may be aggravated when the climate changes or the weather is mildewed. Severe patients have pain and marked soreness, and symptoms such as skin ecchymosis, arthrocele, deformation, difficulty in flexion and extension and the like are caused by repeated attack, chronic unhealing, unsmooth circulation of qi and blood, phlegm turbidity and blood stasis, and blockage of channels and collaterals. Meanwhile, long-term disease causes impairment of healthy qi and consumption of qi and blood, so that symptoms of qi and blood deficiency, liver and kidney deficiency and the like with different degrees can be presented, and the disease is characterized by lingering of healthy qi and pathogenic factors and mixed deficiency and excess. In addition, chronic arthralgia is complicated by exogenous pathogenic factors, which spread to the zang-fu organs from superficial to deep and from meridians, resulting in obstruction of qi and blood in the zang-fu organs.

At present, western medicines for treating rheumatism usually adopt methods of diminishing inflammation, relieving pain, hormone, sealing, ultraviolet irradiation, traction, operation and the like, and have the defects that the western medicines are easy to generate dependence after being taken for a long time, the curative effect is poor, and side effects are more. The traditional Chinese medicine adopts oral traditional Chinese medicine, or adopts massage, acupuncture and moxibustion and the like to relieve the disease. However, if the traditional Chinese medicines are taken for a long time, the compliance of patients is poor, and some traditional Chinese medicines stimulate the stomach and can generate adverse side effects. The modes of massage and acupuncture can only relieve the pain of patients for a while, but can not cure the disease radically.

Disclosure of Invention

Aiming at the problems in the prior art, the invention aims to provide an external traditional Chinese medicine composition for treating rheumatism, a gel paste prepared from the external traditional Chinese medicine composition, and a preparation method and application of the gel paste.

In order to achieve the purpose, the invention adopts the following technical means:

the invention relates to an external traditional Chinese medicine composition for treating rheumatism, which is prepared from the following raw materials in parts by weight:

5-15 parts of pubescent angelica root, 5-15 parts of cassia twig, 1-10 parts of notopterygium root, 1-10 parts of divaricate saposhnikovia root, 1-10 parts of safflower, 1-10 parts of dried ginger, 1-10 parts of large-leaved gentian, 1-10 parts of szechuan lovage rhizome, 1-10 parts of Chinese angelica, 1-10 parts of argy wormwood leaf, 1-5 parts of Chinese herbaceous peony and 1-5 parts of Chinese taxillus twig.

Preferably, the external traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

9 parts of pubescent angelica root, 9 parts of cassia twig, 6 parts of incised notopterygium rhizome, 6 parts of divaricate saposhnikovia root, 6 parts of safflower, 6 parts of dried ginger, 6 parts of large-leaved gentian, 6 parts of szechuan lovage rhizome, 6 parts of Chinese angelica, 6 parts of argy wormwood leaf, 3 parts of Chinese herbaceous peony and 3 parts of Chinese taxillus twig.

Preferably, the external traditional Chinese medicine composition is prepared by the following method:

(1) weighing the raw materials in parts by weight;

(2) adding 70-90% v/v ethanol 8-15 times the volume of the raw materials, reflux extracting for 1-3 times (each for 1-3 hr), filtering the extractive solution, mixing filtrates, and recovering under reduced pressure.

Preferably, in the step (2), 80% v/v ethanol with the volume of 10 times of that of the weighed raw materials is added for reflux extraction for 2 times, 2 hours each time, the extracting solution is filtered, the filtrates are combined, and the pressure is reduced and recovered until each milliliter of the ethanol extracting solution is equivalent to 1.8g of the crude drug, so as to obtain the traditional Chinese medicine.

Furthermore, the invention also provides application of the external traditional Chinese medicine composition in preparing external medicines for treating rheumatism.

Among them, preferably, the external medicine is a patch.

Furthermore, the invention also provides a gel paste for treating rheumatism, which contains the ethanol extract of the external traditional Chinese medicine composition.

Preferably, the gel paste further comprises a matrix component, wherein the matrix component comprises: gelatin, sodium polyacrylate, sodium carboxymethylcellulose (CMC-Na), aluminum chloride, glycerin, zinc oxide, and azone; wherein, zinc oxide is used as a filler; glycerin is used as a humectant; gelatin, sodium polyacrylate and sodium carboxymethylcellulose (CMC-Na) as adhesives; aluminum chloride is used as a cross-linking agent; azone is a penetration enhancer.

A method of making said gel paste comprising the steps of:

uniformly distributing 100g of sodium carboxymethylcellulose and 80g of sodium polyacrylate in 200g of glycerol, adding 1000ml of distilled water, and slowly grinding at a constant speed to obtain a phase A;

adding 100g of gelatin into 1000ml of water for full swelling, heating in a water bath at 50 ℃ until the gelatin is completely dissolved, adding 100g of zinc oxide, and stirring until the gelatin and the zinc oxide are fully and uniformly mixed to form a phase B;

③ 200g of glycerol, 46g of azone, 3g of aluminum chloride and 1000ml of ethanol extract of the external traditional Chinese medicine composition are fully and evenly mixed to be used as a phase C;

fourthly, adding the phase A into the phase B, stirring at a constant speed, then adding the phase C, stirring at a constant speed, coating on a back lining, drying in a baking oven at 50 ℃ for 4h, and taking out to prepare 100 pieces of gel paste with the diameter of 12cm and the weight of 15 +/-1.5 g.

Wherein, preferably, each milliliter of the extracting solution of the external traditional Chinese medicine composition is equivalent to 1.8g of crude drugs.

Compared with the prior art, the invention has the beneficial effects that:

the invention takes radix angelicae pubescentis which is pungent, bitter, slightly warm and can dispel wind-cold-damp evil as a monarch drug, and cassia twig which can induce sweat, release muscles and warm and dredge channels and collaterals is used as an auxiliary drug. The traditional Chinese medicine is prepared by combining folium artemisiae argyi and rhizoma zingiberis which warm the channels and dispel cold to relieve pain, and matching with safflower and rhizoma ligustici wallichii which have the functions of promoting blood circulation and clearing the channels and collaterals, dispersing exterior cold and dispelling wind-damp, notopterygium root which has the functions of dispelling wind-damp, large-leaved gentian which has the functions of expelling wind-damp, dredging the collaterals and relieving pain, angelica which has the functions of enriching the blood and promoting blood circulation, Chinese herbaceous peony which has the functions of nourishing blood and astringing yin, suppressing liver yang and softening liver and relieving pain, and Chinese taxillus which has the functions of tonifying liver and kidney, strengthening bones and muscles and eliminating wind-damp, and a formula which has the functions of promoting blood circulation and nourishing blood, dispelling wind and removing dampness, clearing the channels and activating collaterals, warming the channels and dispelling cold and strengthening the bones.

Detailed Description

The present invention is further described with reference to the following specific examples, which are only illustrative and not intended to limit the scope of the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

Example 1 preparation of an external Chinese medicinal composition for treating rheumatism and its extract

The external traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9 parts of pubescent angelica root, 9 parts of cassia twig, 6 parts of incised notopterygium rhizome, 6 parts of divaricate saposhnikovia root, 6 parts of safflower, 6 parts of dried ginger, 6 parts of large-leaved gentian, 6 parts of szechuan lovage rhizome, 6 parts of Chinese angelica, 6 parts of argy wormwood leaf, 3 parts of Chinese herbaceous peony and 3 parts of Chinese taxillus twig.

Preparing an ethanol extracting solution:

selecting ethanol concentration, solvent volume (ethanol dosage), extraction times and extraction time as investigation factors, adopting a single factor investigation and orthogonal design method, taking the paste yield and the total content of effective components as investigation indexes, and determining the optimal extraction process of the formula medicine as follows:

(1) weighing the raw materials in parts by weight;

(2) adding 80% v/v ethanol 10 times the volume of the raw materials, reflux-extracting for 2 times, each for 2 hr, filtering the extractive solution, mixing filtrates, and recovering ethanol under reduced pressure until the volume of the extractive solution per ml is equal to 1.8g of crude drug.

Example 2 preparation of external use Chinese medicinal composition for treating rheumatism and extract thereof

The external traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5 parts of pubescent angelica root, 10 parts of cassia twig, 5 parts of incised notopterygium rhizome, 6 parts of divaricate saposhnikovia root, 8 parts of safflower, 7 parts of dried ginger, 5 parts of large-leaved gentian, 5 parts of szechuan lovage rhizome, 6 parts of Chinese angelica, 5 parts of argy wormwood leaf, 2 parts of Chinese herbaceous peony and 3 parts of Chinese taxillus twig.

Preparing an ethanol extracting solution:

(1) weighing the raw materials in parts by weight;

(2) adding 85% v/v ethanol 8 times the volume of the raw materials, reflux-extracting for 2 times, each time for 1.5 hr, filtering the extractive solution, mixing filtrates, and recovering under reduced pressure until each ml of extractive solution is equal to 1.8g of crude drug.

Example 3 preparation of external use Chinese medicinal composition for treating rheumatism and extract thereof

The external traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10 parts of pubescent angelica root, 7 parts of cassia twig, 8 parts of incised notopterygium rhizome, 5 parts of divaricate saposhnikovia root, 5 parts of safflower, 8 parts of dried ginger, 7 parts of large-leaved gentian, 7 parts of szechuan lovage rhizome, 5 parts of Chinese angelica, 7 parts of argy wormwood leaf, 3 parts of Chinese herbaceous peony and 5 parts of Chinese taxillus twig.

Preparing an ethanol extracting solution:

(1) weighing the raw materials in parts by weight;

(2) adding 75% v/v ethanol with volume of 12 times into the weighed raw materials, reflux-extracting for 2 times, each time for 2.5h, filtering the extractive solution, mixing filtrates, and recovering under reduced pressure until each ml of extractive solution is equal to 1.8g of crude drug.

EXAMPLE 4 preparation of gel paste for treating rheumatism (rheumatism arthralgia gel paste)

The selection of the type and the dosage of the matrix are key links for the success of the preparation of the gel ointment. The invention selects gelatin, sodium polyacrylate NP-700, sodium carboxymethylcellulose (CMC-Na), aluminum chloride, glycerol and zinc oxide as matrixes, wherein the zinc oxide is a filler; glycerin is used as a humectant; gelatin, sodium polyacrylate NP-700 and sodium carboxymethylcellulose (CMC-Na) are used as adhesives; aluminum chloride is used as a cross-linking agent; azone is a penetration enhancer. The matrix formula and the preparation method of the gel paste are determined by adopting a single-factor investigation and orthogonal design method and taking viscosity and appearance as investigation indexes:

uniformly distributing 100g of sodium carboxymethylcellulose and 80g of sodium polyacrylate NP-700 in 200g of glycerol, adding 1000ml of distilled water, and slowly grinding at a constant speed to obtain a phase A;

③ mixing 200g of glycerin, 46g of azone, 3g of aluminum chloride and 1000ml of ethanol extract of the external traditional Chinese medicine composition prepared in the example 1 uniformly to obtain phase C;

fourthly, adding the phase A into the phase B, stirring at a constant speed, then adding the phase C, stirring at a constant speed, coating the mixture on a back lining, drying the mixture in a baking oven at 50 ℃ for 4 hours, taking out the mixture, and preparing 100 pieces of gel paste with the diameter of 12cm and the weight of 15 +/-1.5 g

The gel paste prepared by the method is dark brown, has a smooth surface, is bubble-free, smooth, particle-free, impurity-free and uniform in color; the preparation is applied to the back of wrist, and can be thrown by hand without falling off.

The usage and dosage are as follows: applied externally. Can be directly applied to affected part joint, and is replaced once a day, with a use period of 5 days.

EXAMPLE 5 preparation of gel paste for treating rheumatism (rheumatism arthralgia gel paste)

The preparation method is the same as example 1 except that the ethanol extract of the external Chinese medicinal composition prepared in example 2 is used as a medicinal ingredient.

EXAMPLE 6 preparation of gel paste for treating rheumatism (rheumatism arthralgia gel paste)

The preparation method is the same as example 1 except that the ethanol extract of the external-use Chinese medicinal composition prepared in example 3 is used as a medicinal ingredient.

EXAMPLE 7 pharmacodynamic study of gel ointment for treating rheumatism (rheumatism arthralgia gel ointment)

First, experimental instrument, medicine and reagent

1 laboratory apparatus

2 Experimental drugs and reagents

Second, experimental animal

84 healthy SD rats with half male and female bodies and weight of 180-. All rats are placed in an environment with room temperature of 24-26 ℃, relative humidity of 50-60%, good ventilation and illumination, and are fed with standard rat feed in a conventional manner, and freely eat and drink water.

Third, Experimental methods and results

1 animal grouping

After being fed for 1 week, 84 rats were randomly divided into a blank group, a model group, a positive control group (a commercial compound arisaema analgesic ointment, which is administered according to the pharmaceutical instruction), a gel ointment low-dose group, a gel ointment medium-dose group and a gel ointment high-dose group, wherein each group contains 14 rats.

2 establishment of rat model for rheumatism (wind-cold-dampness arthralgia)

When the model is made at the 1 st d, the left hind paw of the rat is injected with complete Freund's adjuvant subcutaneously, 0.1ml of each, the rat is induced to generate local inflammation and generate continuous stimulation to the injection site, wherein the blank group is given with equal amount of physiological saline at the same position, after one hour, the rest rats except the blank group are placed in ice water at the temperature of 3-5 ℃, the rat is stood in the ice water and given with proper wind power stimulation for 10min, and the 2 nd d begins to be given with ice water bath and wind power stimulation to the rats of each group except the blank group for 13 days continuously.

3 determination of rheumatism (wind-cold-dampness arthralgia) rat model

The postinflammatory model rat has rough and lusterless hair, reduced appetite and reduced drinking water, prefers warm and prick heaps, has obvious swelling of hind toes and bright and red skin at the swollen part, and the forefoot of the rat has swelling, movement disorder, slope movement and foot licking behaviors in different degrees along with the prolongation of the modeling time, and the success of the modeling is proved by the appearance of the symptoms.

4 method of administration

After the model building is successful, the hair on the back of the rat is removed, the gel ointment and the positive medicine are applied to the back of the rat without the hair, and the administration areas of the low, medium and high dose groups and the positive control group are 1cm multiplied by 1.5cm, 2cm multiplied by 1.5cm, 5cm multiplied by 2.5cm and 1cm multiplied by 1cm respectively. The plaster was changed once a day and the administration was continued for 14 days.

5 Observation index and measurement method

5.1 arthritis AI score

Before and after dosing, each rat was scored according to the scoring method of table 1, the sum of the scores of 4 paws was taken as the final AI score, and the score of each rat was not more than 16 at the highest.

TABLE 1 rat arthritis index score

5.2 measurement of toe volume

The volume of the left hind paw toe of the rat was measured before 1d of the inflammation, 1d before the administration and 1d after the administration.

5.3 measurement of plasma indices

29d, respectively collecting the abdominal aorta blood of each group of rats in a vacuum blood collection tube, standing for 30min, placing in a centrifuge, centrifuging at 3000r/min for 10min to obtain serum, placing the serum in an ultralow temperature refrigerator at-80 ℃ for standby, and detecting the IL-1 beta, IL-6, TNF-alpha and PGE2 levels in the serum of the rats strictly according to the method in the ELISA kit.

6 results of the detection

6.1 arthritis AI score

There was no significant difference (P >0.05) between the normal group, model group, positive control group, low dose group, medium dose group and high dose group 1d before administration, indicating that the degree of lesion was the same and there was no difference in each group. After administration, compared with a model group, the low-dose group, the medium-dose group and the high-dose group have very significant differences (P is less than 0.01), which shows that the gel paste can significantly inhibit the development of the inflammation of the rats in the rheumatism model. The results are shown in Table 2.

Table 2 comparison of AI scores for groups of rats (n-14,

)

note: in comparison with the set of models,^*P＜0.01

6.2 toe volume comparison of rats in each group

There was no significant difference in toe volume between groups 1d before molding (P >0.05), indicating that each group was an experiment performed on the same basis. Compared with the blank group, the toe volume of the rats in the model group is obviously increased at 1d before the drug administration, and the model group has extremely obvious difference (P is less than 0.01), which indicates that the model is successfully made. Compared with the model group, the toe volume of the positive control group, the low-dose group, the medium-dose group and the high-dose group is reduced (P is less than 0.05) after the administration, which shows that the gel paste of the invention can obviously reduce the foot swelling degree of the rheumatism model rat. The results are shown in Table 3.

Table 3 comparison of toe volumes in rats of each group (n-14,

)

note: in comparison with the blank set, the results,^*p is less than 0.01; in comparison with the set of models,^▲P＜0.01

6.3 comparison of the content of IL-1 beta, IL-6, TNF-alpha and PGE2 in the serum of rats in each group

The results are shown in Table 4.

Table 4 comparison of the content of IL-1 β, IL-6, TNF- α and PGE2 in the serum of each group of rats (n-14,

)

note: in comparison with the blank set, the results,^*p is less than 0.01; in comparison with the set of models,^▲P＜0.05

as is clear from Table 4, the serum levels of IL-1. beta., IL-6, TNF-. alpha., and PGE2 in the rat serum of the model group were all significantly increased (P < 0.01) as compared with the blank group, and the water levels of IL-1. beta., IL-6, TNF-. alpha., and PGE2 in the rat serum of each administration group were significantly decreased (P < 0.05) as compared with the model group, and the effect was most significant in the high dose group. The experimental result shows that the gel paste can obviously reduce the content of IL-1 beta, IL-6, TNF-alpha and PGE2 in a rat body of a rheumatism model, inhibit the generation of inflammatory factors, reduce the content of tumor necrosis factors and prostaglandin 2 in the body, control the inflammatory process route by inhibiting the generation of inflammation and play a role in treating anemofrigid-damp arthralgia.

The invention adopts a method of combining ice water bath and wind power stimulation to establish an animal model, the success rate is higher, and the rat has the symptoms of redness, swelling, inconvenient movement and the like. Compared with the model group, the AI score and toe volume of the rats in each administration group are reduced in different degrees, and the contents of IL-1 beta, IL-6, TNF-alpha and PGE2 in serum are all obviously reduced, which shows that the gel paste of the invention inhibits the generation and development of inflammation by reducing the levels of inflammatory factors and tumor necrosis factors in the serum of the rats in the rheumatism model, thereby playing the role of treating rheumatism.

Claims

1. The external traditional Chinese medicine composition for treating rheumatism is characterized by being prepared from the following raw materials in parts by weight:

2. The external traditional Chinese medicine composition of claim 1, which is prepared from the following raw materials in parts by weight:

3. The topical Chinese medicinal composition according to claim 1 or 2, which is prepared by the following method:

(1) weighing the raw material medicines according to the parts by weight of the raw material medicines in the claim 1 or 2;

4. The method of claim 3, wherein in step (2), 80% v/v ethanol with 10 times volume is added into the weighed raw materials for reflux extraction for 2 times, each time for 2h, the extract is filtered, the filtrates are combined, and the filtrate is recovered under reduced pressure until the volume of the ethanol extract per ml is equivalent to 1.8g of crude drug, thus obtaining the traditional Chinese medicine.

5. Use of the topical Chinese medicinal composition of any one of claims 1-4 in the manufacture of a topical medicament for the treatment of rheumatic diseases.

6. The use of claim 5, wherein the topical medicament is a patch.

7. A gel paste for treating rheumatism, characterized in that the gel paste contains an ethanol extract of the topical Chinese medicinal composition of any one of claims 1 to 4.

8. The gel paste of claim 7 further comprising a base component, said base component comprising: gelatin, sodium polyacrylate, sodium carboxymethylcellulose (CMC-Na), aluminum chloride, glycerin, zinc oxide, and azone; wherein, zinc oxide is used as a filler; glycerin is used as a humectant; gelatin, sodium polyacrylate and sodium carboxymethylcellulose (CMC-Na) as adhesives; aluminum chloride is used as a cross-linking agent; azone is a penetration enhancer.

9. A method of preparing the gel paste of claim 7 or 8, comprising the steps of:

③ mixing 200g of glycerol, 46g of azone, 3g of aluminum chloride and 1000ml of ethanol extract of the external traditional Chinese medicine composition according to any one of claims 1 to 4, and taking the mixture as a phase C;

10. The method of claim 9, wherein the amount of ethanol extract per ml of the topical Chinese medicinal composition is 1.8g crude drug.