CN1679861A - medicine for toothache - Google Patents

Abstract

The invention relates to a medicine for treating toothache and a preparation method thereof. The medicine has the effects of clearing heat and detoxifying, dispelling wind and relieving pain, and is suitable for diseases such as wind-fire and toothache. The medicine is prepared from clove leaves and asarum as raw materials according to a certain weight ratio, and has the characteristics of small toxic and side effects, remarkable effect and the like.

Description

medicine for toothache

technical field

The invention relates to a medicine for treating toothache, which is used for clearing heat and detoxification, dispelling wind and relieving pain, and treating toothache diseases such as wind-fire toothache.

Background technique

Toothache syndromes are very common in clinical practice. According to the second national oral health epidemiological survey, the caries rate of adult permanent teeth in China is 49.88%, and that of children's deciduous teeth is 76.55%. Teeth chewing is the first step in the digestive system. Process, dental disease has a very important impact on human health. Long-term dental disease can cause inflammation and ulcers in the digestive system, especially wind-fire toothache, which makes the patient's bedroom uneasy. So far, there is no special medicine for toothache. Generally, analgesics are used, but the analgesic effect cannot fundamentally treat the toothache itself. Western medicine often uses drilling to kill the nerves. After many times of treatment, it causes great pain to the patient, and the killing of the nerves is not complete. , relapse again after blocking the tooth, making the patient miserable; and the traditional Chinese medical science lacks the special-purpose medicine that is specially used in the treatment of toothache disease syndrome, and the existing variety in the market is less, and curative effect is all insignificant, can not effectively cure toothache disease.

Contents of the invention

The object of the present invention is exactly to provide a kind of medicine for treating toothache and preparation method thereof for the deficiency of prior art. This medicine has the effects of clearing heat and detoxifying, dispelling wind and relieving pain. It is used for wind-fire toothache. It is mainly suitable for paroxysmal toothache. Symptoms such as hi cold drink.

The present invention is achieved by the following technical solutions:

(1) Prescription and parts by weight of raw material medicine:

Clove leaves 80-110 Asarum 6-12

Wherein the preferred parts by weight of bulk drug are:

Clove leaves 100 Asarum 10

(2) Process method:

a) taking clove leaves and Asarum of equal weight, pulverizing into fine powder respectively, for subsequent use;

b) Separately take clove leaves with the difference in weight ratio, grind them into coarse powder, add water to decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.05 to 1.15; Add the clove leaf fine powder obtained in step a) above, mix well, dry at low temperature (below 60°C), pulverize into fine powder, stir and mix with the asarum fine powder obtained in step a) above, and sieve to make a powder; or pack into capsules to make capsules; or add water-soluble excipients to mix, use appropriate ethanol to make soft materials, and make granules through a granulator; or add starch, crush, sieve, granulate, dry, and tablet, that is Get Tablets.

Experimental part:

1. Stability test

For the sample of this batch number, two methods, such as preliminary stability test at room temperature and observation for two years, were used to observe the characteristics of the drug, water content inspection, and the time limit for disintegration of the content. It is stable in nature and can be stored for more than two years.

2. Toxicology

1, acute toxicity test: the medicine of the present invention fails to measure LD ₅₀ to mouse gavage administration, and the determination of maximum tolerated dose gives the maximum volume (5g/kg) of the maximum concentration 30% that animals accept within seven days without one death and Toxic reaction. Therefore, the therapeutic dose for adults (50 kg) is calculated to be 3.6 g, which is equivalent to 625 times the clinical dosage.

2. Long-term toxicity test: select 60 healthy rats, half male and half male, randomly group them into groups, and carry out the test. The results show that the high-dose group, with an average of 4.8g/kg, is equivalent to 66.7 times the clinical adult dosage based on oral administration. After 30 days of such a large amount of medication, no abnormal changes were found in the liver, heart, lung, spleen, kidney, stomach, brain, etc. of the animals through gross autopsy and histopathological examination. It can be considered that the medicine of the present invention has no toxic reaction.

3. Pharmacodynamics

1. Analgesic experiment: the drug of the present invention was intraperitoneally injected with drug concentration of 0.6% HACO, 0.3ml/only compared with the normal saline control group. After 15 minutes, it was observed that the abdomen was sticking to the ground, showing shrinkage and stretching, buttocks were crooked, etc. The results showed that toothache Ning can significantly inhibit the writhing reaction caused by HAD. The heat pull method, the medicine of the present invention can significantly inhibit the writhing reaction caused by HAD. The heat pull method test measures the pain before administration, and then the administration group takes a certain amount of the medicine of the present invention orally. The positive control group (morphine hydrochloride) was injected subcutaneously, and the control group took orally the same volume of normal saline, and the pain threshold of each mouse was measured. The results showed that the pain threshold of the oral administration group could be significantly improved no matter whether it was compared within itself or between groups.

2. Anti-inflammatory effect: Select the effect of xylene to cause ear inflammation in rats. The administration group, the cortisone group, the blank group, and the mice were executed after 80 minutes. The difference of ear weight is used as degree of swelling, surveys its inhibitory rate, and the result shows, the medicine of the present invention of a certain dose can obviously hold and suppress xylene and cause mouse ear inflammation swelling effect, simultaneously, also shows to mouse peritoneal vascular permeability experiment, large Dosage The medicament of the present invention has the effect of significantly reducing the permeability of blood vessels in the peritoneal cavity of mice.

3. Effects on normal blood pressure and respiration of anesthetized rabbits: Animals are anesthetized with urethane (1 g/kg), and injected intravenously with 0.5 ml/kg (1:5) of the medicine of the present invention, which has no effect on blood pressure and respiration of rabbits.

4. Influence on gastrointestinal peristalsis, administration group, drug group of the present invention and blank group evenly give ink 0.2ml, calculate the percentage that the distance that each group of mouse ink moves in the small intestine accounts for the total length of the small intestine, the results show that the present invention Drugs can enhance the motility of gastrointestinal tract in mice.

5, bacteriostasis test, select B streptococcus, staphylococcus aureus, meningococcus meningitidis, bacillus typhimurium, lactobacillus, diplococcus neizii to carry out the bacteriostasis test result of medicine of the present invention, medicinal liquid of the present invention ( 1:10) has a high antibacterial effect on Streptococcus B, Lactobacillus and Neisseria Neisseria. No antibacterial effect on Staphylococcus aureus.

4. Clinical Trial Structure

From September 15, 1987 to October 20, 1992, 739 cases were clinically observed in the First Affiliated Hospital of Harbin Medical University.

1, medicine of the present invention, through clinical verification, to acute pulpitis (144 examples) clinical effective rate 97.9%, compares with simple dental specialist treatment (control group 45 examples) clinical curative effect, has significant difference.

2. There is a significant difference between the 38 cases of acute suppurative pulpitis and the control group (simply dental specialist treatment).

3. There are significant differences between the 26 cases of chronic pulpitis (non-atresia) and the control group treated with simple dental treatment.

4. There is also a significant difference between 42 cases of acute exacerbation of chronic pulpitis and 30 cases of simple dental treatment.

5. There is also a significant difference between 30 cases of retrograde pulpitis and 24 cases of simple dental treatment.

6. The drug group of the present invention and the antibacterial control drug group, the effective rate of the drug group of the present invention is 97.9%, that of the indomethacin group is 72%, and that of the spiramycin group is 64%.

Overall analysis and statistical processing, X ² = 11.91 P = <0.001, total effective rate X ² = 37.30 P < 0.0001 in the drug treatment group and simple dental treatment, there is a significant difference, the number of recovery in the second group observation group and the control group X ² =6.04 P<0.01, the total effective number X ² =9.07 P<0.05, there is a significant difference.

7. All cases were observed, and no adverse reactions were found during the observation process of medication.

8. Through clinical verification, the function of medicine of the present invention cures mainly, has the effect of clearing heat and purging fire, reducing swelling and dispelling pain, and is an effective medicine for clinically treating pulpitis, periodontitis, gingivitis and various wind-fire toothaches. Stable in quality, easy to store and carry, especially suitable for clinical promotion and use.

5. Acute Toxicity Test

Test sample preparation: take the traditional Chinese medicine powder of the present invention, add water to make a certain concentration of the medicinal powder suspension of the present invention for testing. After several pre-tests, 30% (g/v) was its maximum concentration. The dosage is calculated according to the weight of the Chinese medicine powder in the capsule.

1. Determination of median lethal dose (LD ₅₀ ):

(1) Preliminary test: 100% animal death dose could not be found out as a result of the preliminary test.

(2) Formal test: one oral gavage administration, dose interval 1:0:8. The highest dose group was dosed with the largest volume at the maximum concentration that the animals could accept. Results Table 1.

Table 1 group Number of animals (only) Dose (g/kg) Feed volume ( ml/only ) and concentration Number of deaths within seven days (only) 1 10 15.0 1.00 (3:10) 0 2 10 12.0 0.80 (3:10) 0 3 10 9.6 0.64 (3:10) 0 4 10 7.7 0.51 (3:10) 0 5 10 6.1 0.41 (3:10) 0

As can be seen from Table 1, by 6.1 ~ 15g/kg dose, mice are fed with the drug powder suspension of the present invention, and no mouse dies in seven days, and no toxic reaction is observed in mice after administration. Because the administration concentration was 30% and the administration volume (1.0ml/mouse) had reached the maximum, the test failed to measure the LD ₅₀ of mice gavaged with the drug powder suspension of the present invention once.

2. Determination of maximum tolerated dose: within 24 hours, intragastric administration was given to mice three times, and the dose (15g/kg) of the maximum volume (1ml/20g) under the maximum concentration (30%) accepted by the animal was given each time (15g/kg). Within 7 hours, there was no mouse death or toxic reaction within seven days.

Calculate the total dosage in one day to be 45g/kg, and the daily treatment dosage for adults (50kg) is 3.6g, which is equivalent to clinical dosage=45g%kg÷3.6g/50kg=625 times through derivation.

3. Adverse reactions: within 24 hours, after the third consecutive administration, 1/3 of the animals were found to have loose stools 2 hours after the mice were gavaged, that is, the total dose of 45g/kg was the dose that caused loose stools. The following mice failed to show this symptom.

6. Pathological examination report of long-term toxicity test

1. Test substance: The drug of the present invention is provided by Harbin Xinxing Institute of Traditional Chinese Medicine, batch number: 930928

2. Animal grouping: 60 healthy white rats of Wistar strain, half male and half male, supplied by Harbin Gongnong Animal Farm, animal production certificate number: 007. They were randomly divided into three groups, 20 in each group, 10 male and 10 male.

3. Dosage, route:

Low-dose group: 2.4g/kg dose (equivalent to 33.3 times adult clinical daily treatment dose).

High-dose group: 4.8g/kg dose (equivalent to 66.6 times of adult clinical daily treatment dose).

Gavage rats with 12 and 24% drug powder suspension 2ml/100g body weight of the present invention once a day according to the above dose, for 4 consecutive weeks.

4. Inspection results: 24 hours after the last administration, half of the animals in each group were killed alive. According to the conventional treatment method, the animal organs were taken out, fixed with 10% formalin solution, wrapped in paraffin, sliced, and stained with HE , using an optical microscope for the pathological examination of the blank control group and the high-dose group, the results showed that the high-dose group compared with the blank control group, the heart, liver, spleen, lung, kidney, stomach, brain, adrenal gland, testis, ovary , small intestine and other organs no toxic pathological changes.

Although the low-dose group had been preserved, no abnormal lesions were found in the high-dose group, so no further histological examination was performed.

Histopathological examination results of long-term toxicity test in rats:

The tissue structure of the heart, liver, spleen, lung, kidney, stomach, brain, adrenal gland, testis, ovary, small intestine and other organs of the experimental animals in each group was normal, and no pathological changes such as degeneration and necrosis were seen. The congestion of the lungs, spleen, and kidneys of a few animals may be related to the poor blood flow caused by not cutting off the head in time when the animals were sacrificed. There was a small amount of inflammatory cell infiltration in the lung tissue of a small number of animals in the administration group and the blank control group, which may be the inflammatory reaction caused by mistaken infusion into the lungs during administration and water supply. Focal pulmonary hemorrhage was seen in a small number of drug administration groups and the blank control group, and no hemosiderin deposition was seen in the hemorrhage focus, so it may be caused by squeezing the lungs when handling animals, resulting in rupture and bleeding of pulmonary blood vessels.

Compared with the blank group, the high-dose administration group showed no dose-dependent pathological changes, so it may be that there was no toxic reaction in the histopathological examination of the experimental animals in the administration group. See Table 5-1 and Table 5-2.

Table 5-1 pathological examination result of drug rat long-term toxicity test of the present invention organ tissue lesions Blank control group high dose group Heart cell degeneration 0 0 cell necrosis 0 0 Inflammatory cell moist 0 0 Liver and spleen blood stasis 0 0 cell degeneration 0 0 cell necrosis ±(2) ±(1) blood stasis +(2) +(3) necrosis 0 0 Inflammatory cell infiltration 0 0 blood stasis +(2) +(3) lung edema 0 0 bleeding +(1) +(2) Inflammatory cell infiltration ±(2) ±(1) kidney renal tubular epithelial degeneration 0 0 renal tubular epithelial necrosis 0 0 Interstitial blood stasis +(3) +(2) Inflammatory cell infiltration 0 0 Stomach Mucosa hyperemia 0 0 Myometrial cell infiltration 0 0 mucosal epithelial degeneration 0 0 mucositis cell infiltration 0 0 mucosal epithelial necrosis 0 0 brain Nerve cell congestion 0 0 Purkinje cell metamorphosis 0 0 cell degeneration 0 0

Table 5-2 Pathological examination results of drug rat long-term toxicity test of the present invention organ tissue lesions Blank control group high dose group adrenal gland cell degeneration 0 0 cell necrosis 0 0 bleeding 0 0 Inflammatory cell infiltration 0 0 testis cell degeneration 0 0 cell necrosis 0 0 Inflammatory cell infiltration 0 0 ovaries endometrial hyperplasia 0 0 atrophy of endometrial glands 0 0 endometritis cell infiltration +(1)++(1) ++(2) muscle cell degeneration 0 0 muscle cell necrosis 0 0 Myometrial cell infiltration 0 0 small intestine Mucosa hyperemia 0 0 mucosal epithelial degeneration 0 0 mucosal epithelial necrosis 0 0 mucositis cell infiltration 0 0 muscle cell degeneration 0 0 muscle cell necrosis 0 0

specific embodiment

The present invention will be further described below in conjunction with the examples.

Example 1:

a) take by weighing 100g clove leaves and Herba Asarum respectively, and then pulverize into fine powder respectively, and set aside;

b) Take another 900g of clove leaves, crush them into coarse powder, add water and decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.15; add the cloves obtained in the above step a) Fine leaf powder, mixed, dried at low temperature (below 60°C), crushed into fine powder, stirred and mixed with Asarum fine powder obtained in step a) above, sieved, packed into capsules and made into 1000 capsules to obtain capsules .

Example 2:

a) take by weighing 60g clove leaves and Herba Asarum respectively, then pulverize into fine powder respectively, and set aside;

b) Take another 740g clove leaves, crush them into coarse powder, add water and decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.10; add the cloves obtained in the above step a) Leaf fine powder, mixed, dried at low temperature (below 60°C), crushed into fine powder, stirred and mixed with the asarum fine powder obtained in step a) above, and sieved powder.

Example 3:

a) take by weighing 120g clove leaves and Herba Asarum respectively, then pulverize into fine powder respectively, and set aside;

b) Take another 980g clove leaves, crush them into coarse powder, add water and decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.15; add the cloves obtained in the above step a) Fine leaf powder, mixed, dried at low temperature (below 60°C), crushed into fine powder, stirred and mixed with Asarum fine powder obtained in step a) above, sieved, added appropriate amount of dextrin and mixed, made with appropriate ethanol Soft materials, made into granules through a granulator.

Example 4:

a) take by weighing 80g clove leaves and Herba Asarum respectively, then pulverize into fine powder respectively, and set aside;

b) Take another 920g of clove leaves, crush them into coarse powder, add water and decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.15; add the cloves obtained in the above step a) Fine leaf powder, mixed, dried at low temperature (below 60°C), crushed into fine powder, stirred and mixed with Asarum fine powder obtained in step a) above, sieved, added starch, crushed, sieved, granulated, and dried , Tablets, that is, tablets.

Claims (3)

1, a kind of medicine for the treatment of toothache is characterized in that it is made of the crude drug of following weight ratio: Clove leaves 80-110 Asarum 6-12. 2. The medicine for treating toothache according to claim 1, characterized in that it is made of the following raw materials in weight ratio: clove leaves 100 asarum 10. 3. The preparation method for treating toothache according to claim 1 or 2, characterized in that it comprises the following steps: a) taking clove leaves and Asarum of equal weight, pulverizing into fine powder respectively, for subsequent use; b) Separately take clove leaves with the difference in weight ratio, crush them into coarse powder, add water to decoct twice for 1.5 hours each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.05 to 1.15; Add the clove leaf fine powder obtained in step a) above, mix well, dry at a low temperature below 60°C, pulverize into fine powder, stir and mix with the asarum fine powder obtained in step a) above, and sieve to make a powder; or pack into capsules Made into capsules; or mixed with water-soluble excipients, made into soft materials with appropriate ethanol, and made into granules through a granulator; or added with starch, crushed, sieved, granulated, dried, and compressed to obtain tablets agent.