CN110917329A

CN110917329A - Application of Chaihu Jia Longgu Muli Tang and Hua Chai Lu and Chaihu Guizhi Tang in preparing medicine for treating sweating type hand-foot-and-mouth disease

Info

Publication number: CN110917329A
Application number: CN201911368159.8A
Authority: CN
Inventors: 王新锋; 邓安远; 涂华新; 李萌; 余玛俐; 樊伊娜; 彭虎
Original assignee: Jiujiang University
Current assignee: Jiujiang University
Priority date: 2019-12-26
Filing date: 2019-12-26
Publication date: 2020-03-27

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a radix bupleuri and dragon bone oyster soup and application thereof as well as a Hua Chai and Gui Zhi soup in treating patients with stage 1 and stage 2 hand-foot-and-mouth disease sweating type. Clinical experiments show that the invention has obvious advantages and statistical differences in healing, significant effect and effective population. From the specific symptoms, the advantages of the experimental group in three symptoms of rash distribution, food intake reduction and dry mouth and lips have statistical significance; has advantages in drooling, listlessness, dysphoria, easy convulsion, emesis, dysphoria, limb shaking, and myasthenia without statistical difference.

Description

Application of Chaihu Jia Longgu Muli Tang and Hua Chai Lu and Chaihu Guizhi Tang in preparing medicine for treating sweating type hand-foot-and-mouth disease

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a radix bupleuri and keel oyster soup and a cutting method thereof, and an application of a radix bupleuri and cassia twig soup in treating patients with stage 1 and stage 2 hand-foot-and-mouth disease sweating type.

Background

The hand-foot-and-mouth disease is an infectious disease caused by enterovirus, mostly occurs in children under 5 years old, shows that the parts of mouth pain, anorexia, low fever, hands, feet, oral cavity and the like have small herpes or small ulcer, most of children can self-heal for about one week, and a few children can cause complications such as myocarditis, pulmonary edema, aseptic meningoencephalitis and the like. The disease of some serious children will develop quickly and lead to death.

The Western medicine treatment for the hand-foot-and-mouth disease is standardized in a hand-foot-and-mouth disease diagnosis and treatment guideline published by the State health Commission in 2018, wherein the Western medicine treatment for the hand-foot-and-mouth disease is clearly indicated that ' no specific anti-enterovirus medicine exists at present ', interferon α spray/atomization or ribavirin intravenous drip is recommended to have certain curative effect in early use ', symptomatic treatment measures comprise positive control of high fever, resistance to convulsion, reduction of intracranial pressure, improvement of vascular activity (aiming at patients in early stage of III cardiopulmonary dysfunction), and measures such as gamma globulin, glucocorticoid and mechanical ventilation, in a word, the specific anti-virus medicine for treating the hand-foot-and-mouth disease is still lacking in the Western medicine at present, and symptomatic support treatment is mainly used (Cuiyai research for treating the hand-foot-and mouth disease lung-spleen damp-heat syndrome by adding and reducing Ganlu disinfectant pill, university of Gansu university of traditional Chinese medicine, and university of.

In the guidelines for pediatric clinical practice of traditional Chinese medicine, hand-foot-and-mouth disease (revision), 2016 (th edition), hand-foot-and-mouth disease is classified into common syndrome and variable syndrome. For syndrome of pathogen invading lung and spleen, it is modified with Ganlu Xiaodu Dan; for syndrome of exuberant damp-heat-toxicity, it is combined with pestilence-clearing and toxicity-relieving herbs. For the syndrome of transformation with invasion of pathogenic factors into heart and liver, it is modified with Ling jiao Gou Tang; for the syndrome of pathogenic toxin invading the heart, it is modified with Ge Gen Huang Qin Huang Lian Tang; for syndrome of pathogen damaging heart and lung, it is treated with Ji jiao Li Huang Wan and Shen Fu Tang; for syndrome of dampness-toxicity damaging collaterals, it is modified with Si Miao Wan.

The oral traditional Chinese medicine decoction for treating the hand-foot-and-mouth disease comprises 60 cases of treating the hand-foot-and-mouth disease by using a Dazi prescription (Chengyangming and the like, Chinese traditional medicine emergency, 2010), 102 cases of treating the child hand-foot-and-mouth disease by using a dampness-resolving and heat-clearing decoction (Shiyinong, Chinese traditional medicine emergency, 2010) and treating the hand-foot-and-mouth disease by using a Dazi decoction for clearing away heat and toxic materials (Yang Chuan Hemerocallis, Chinese traditional medicine information journal, 2009). Clinical observation of three-bean Yinqiao powder (Yi Wei Nu, Guangming TCM 2009) for treating infantile hand-foot-and-mouth disease and the like mostly used for treating eruption stage I.

The external washing treatment of the hand-foot-and-mouth disease, such as external washing treatment of 41 cases of pediatric hand-foot-and-mouth disease skin rashes (Li et al, Chinese sanitary standard, 2019), external washing treatment of 44 cases of common hand-foot-and-mouth disease by combining a traditional Chinese medicine with a heat toxin Ning (Liangsheng et al, Chinese folk medicine, 2016), oral and external washing treatment of 72 cases of hand-foot-and-mouth disease by combining five flavors of disinfectant and Jiawei with a heat toxin Ning injection, oral and external washing treatment of Yinqiao toxin Qing san (Lymphinium Chiense et al, New traditional Chinese medicine, 2010), external washing treatment of 112 cases of pediatric hand-foot-and-mouth disease (common type) by using a traditional Chinese medicine (Dongcui red et al, Jiangsu medicine, 2010), external washing treatment of 60 cases of hand-foot-and-mouth disease by using a self-prepared heat-toxin-clearing decoction (Wang Ying Hua, J.W.W.J.W.W.C., journal, 2004).

In conclusion, in the existing western medicine treatment scheme for the hand-foot-and-mouth disease, no specific anti-enterovirus medicine is available at present, interferon α spray/atomization or ribavirin intravenous drip is generally recommended, a certain curative effect is achieved in early use, and the medication effect has great limitation, while the traditional Chinese medicine treatment scheme takes heat clearing and detoxifying as a basic idea and is mostly used in the eruption stage I, but the eruption stage I is transmitted to the nerve affected stage II after 1-5 days, and a treatment window is missed after a slight delay, so that the search for an effective medicine for treating the early hand-foot disease is particularly important.

Disclosure of Invention

The invention firstly uses the bupleuri radix, the dragon bone and the oyster soup and the bupleurum cassia twig soup for treating the sweating type hand-foot-and-mouth disease in the eruption stage 1 and the nerve affected stage 2.

The invention relates to an oral liquid medicine of a decoction of radix bupleuri, keel and oyster, an external liquid medicine of the decoction of radix bupleuri, keel and oyster and an oral liquid medicine of a decoction of radix bupleuri, keel and oyster. Now, the description is as follows.

1. Bupleuri and Os Draconis and Concha Ostreae decoction (oral liquid)

The formula of the decoction of radix bupleuri, keel and oyster is as follows:

60-125g of bupleurum, 20-45g of codonopsis pilosula, 20-45g of poria cocos, and,

20-45g of dragon bone, 20-45g of oyster, 20-45g of cinnamon,

20-45g of magnetite, 20-45g of raw scutellaria baicalensis, 20-100g of ginger processed pinellia tuber,

30-60g of raw rhubarb, 20-45g of ginger (cut) and 6-12 jujubes (torn).

In clinical use, the preferable prescription of the bupleurum root and dragon bone oyster soup (oral liquid medicine) is as follows:

60g of bupleurum, 20g of codonopsis pilosula, 20g of tuckahoe,

20g of dragon bone, 20g of oyster, 20g of cinnamon,

20g of magnetite, 20g of raw scutellaria baicalensis, 20g of ginger processed pinellia ternate,

30g of raw rhubarb, 20g of ginger (cut) and 6 jujubes (torn).

The decoction method of the decoction of the bupleurum root, the dragon bone and the oyster comprises the following steps:

the method comprises the following steps: soaking the above materials in 800 ml of water at normal temperature and 1200ml of water in an earthenware pot for 45-75 minutes;

step two: after boiling with strong fire, the mixture is changed into small fire, and about 250-350ml of liquid medicine is boiled for standby.

The decoction of Bupleurum, Os Draconis and Concha Ostreae originated from Shanghai treatise on Shanghai, is mainly used for treating liver depression, phlegm retention and gallbladder depression, regulating qi and activating blood circulation, clearing heat and lowering fire, removing phlegm for resuscitation, relieving convulsion and tranquilizing mind, and treating epilepsy, palpitation and the like. In modern clinic, the decoction of radix bupleuri, keel and oyster is mainly applied to:

1. neurological disorders: including epilepsy, neurosis, obsessive-compulsive neurosis, vascular dementia, angioneurotic headache, migraine, and facial neuritis.

2. Mental diseases: psychotic disorder, schizophrenia, depression, anxiety.

3. Cardiovascular diseases: coronary heart disease, angina pectoris complicated with premature ventricular contraction, hypertension, premature ventricular contraction, cardiovascular neurosis, hyperlipoproteinemia, and cardiac neurosis.

4. Digestive system diseases: chronic atrophic gastritis, non-erosive gastroesophageal reflux disease, constipation, chronic viral hepatitis B, and alcoholic cirrhosis.

5. Other diseases: meniere's disease, climacteric syndrome, sexual impotence, premature ejaculation, sleep disorder, cerebral ischemic stroke, acute cerebral infarction, Parkinson, amenorrhea, and intractable urticaria.

In the invention, the radix bupleuri and dragon bone oyster soup is firstly applied to the treatment of the hand-foot-and-mouth disease. Bupleuri radix, Scutellariae radix and rhizoma Pinelliae in bupleuri radix and Os Draconis Concha Ostreae decoction can be used for relieving fever and tranquilizing, and can be used for treating dysphoria and emesis of stage 2 nervous system affected stage (fullness in chest); os Draconis and Concha Ostreae have tranquilizing effect, and can be used for treating central nervous system injury in stage 2 nervous system affected stage of stage 2 nervous system affected stage; the cassia twig, the tuckahoe, the dragon bone and the oyster can enhance the treatment effect of the mental nervous system; the rhubarb can clear away pathogenic heat of liver and gallbladder, dredge intestinal rubbish and viruses and has the functions of diminishing inflammation and easing pain; the ginger, the red date and the radix codonopsitis have the functions of protecting stomach qi and enhancing drug effect.

2. Cutting Bupleurum root, dragon bone and oyster soup (external liquid)

On the basis of treating the hand-foot-and-mouth disease anhidrosis patient by using the bupleuri radix and keel oyster soup, the externally applying treatment can be carried out on the patient by using the soup prepared by cutting the bupleuri radix and keel oyster soup so as to improve the treatment speed and effect.

The formula of the decoction of radix bupleuri, keel and oyster is as follows:

60-125g of radix bupleuri, 20-45g of codonopsis pilosula, 20-45g of poria cocos, and,

20-45g of dragon bone, 20-45g of oyster, 20-45g of cinnamon,

20-45g of magnetite, 20-45g of raw scutellaria baicalensis, 20-100g of prepared pinellia ternate,

30-60g of raw rhubarb, 20-45g of ginger (cut), 6-12 jujubes (torn) and 30g of prepared aconite root.

In clinical use, the preferable formula of the decoction of bupleurum root, dragon bone and oyster shell (externally applied liquid medicine) is as follows:

125g of radix bupleuri, 45g of codonopsis pilosula, 45g of poria cocos,

45g of dragon bone, 45g of oyster, 45g of cinnamon,

45g of magnetite, 45g of raw scutellaria baicalensis, 60g of prepared pinellia ternate,

60g of raw rhubarb, 45g of ginger (cut), 12 jujubes (torn) and 30g of prepared aconite.

The decoction method of the externally applied liquid medicine prepared by cutting the decoction of radix bupleuri, keel and oyster comprises the following steps:

the method comprises the following steps: placing 2000 ml of normal temperature water and 2600ml of the traditional Chinese medicine decoction pieces into an earthen pot for soaking for 45-75 minutes;

step two: boiling with strong fire, decocting with slow fire to obtain 1000ml-1400 ml medicinal liquid, removing residue, and washing with casserole;

step three: pouring the liquid medicine in the step two into the cleaned earthenware pot again, boiling the liquid medicine with strong fire, and then boiling the liquid medicine with slow fire to obtain about 500-700ml of liquid medicine. And (5) standby.

Compared with the oral liquid of the Bupleurum root, dragon bone and oyster decoction, the external liquid of the Bupleurum root, dragon bone and oyster decoction is added with the prepared aconite root, and the dosage is changed. In clinical practice, the curative effect for treating the anhidrosis hand-foot-mouth disease is enhanced after the radix aconiti lateralis preparata is added and the external application is carried out, and no adverse reaction is found.

3. Bupleuri and ramulus Cinnamomi decoction

The prescription of the bupleurum-cassia twig decoction comprises:

60-125g of radix bupleuri, 20-45g of prepared pinellia tuber, 20-45g of codonopsis pilosula,

20-45g of raw scutellaria baicalensis, 15-30g of honey-fried licorice root, 20-45g of cassia twig,

20-45g of white peony root, 20-45g of ginger (cut) and 6-12 Chinese dates (torn).

Preferably, the prescription of the bupleurum-cassia twig decoction comprises the following components:

60g of radix bupleuri, 20g of prepared pinellia tuber, 20g of codonopsis pilosula,

20g of scutellaria baicalensis, 20g of honey-fried licorice root, 20g of white paeony root,

20g of cassia twig, 20g of ginger (cut) and 6 jujubes (torn).

The decoction method of the bupleurum and cassia twig decoction comprises the following steps:

the method comprises the following steps: soaking 800-2400ml of normal temperature water and the traditional Chinese medicines in an earthen pot for 50-70 minutes;

The chaihu Guizhi Tang is prepared from Xiaochaihu Tang and Guizhi Tang in Shang Han Lun, and is mainly used for treating fever, aversion to cold, limb pain and other symptoms caused by taiyang deficiency syndrome. With the intensive clinical application and research, the compound has a plurality of new applications. The formula can regulate nutrient-defensive qi and blood, harmonize exterior and interior, sooth liver and promote bile flow, has wide clinical syndrome treatment range, is applied to internal medicine, gynecology, pediatrics, dermatology and ophthalmology, and the bupleurum-cassia twig decoction can treat skin diseases and nervous system diseases clinically.

According to clinical observation, the inventor shows that before some children suffering from hand-foot-and-mouth disease eruption, the children are accompanied with symptoms of fever, cough, salivation, appetite reduction and the like, and the children are high in similarity with cold. After eruption, infants suffering from hand-foot-and-mouth disease are often accompanied with irritability and crying, and the original cold symptoms are easily covered. Therefore, the treatment is more reliable by using the bupleurum-cassia twig decoction to relieve the exterior syndrome of cold.

The invention combines the bupleuri radix and cassia twig decoction and the radix bupleuri and keel oyster decoction and the cutting thereof, is applied to the treatment of patients with sweating type hand-foot-and-mouth disease in stage 1 or stage 2, and can improve the curative effect of the radix bupleuri and keel oyster decoction and accelerate the treatment process.

The following explains the application points of the Chinese medicinal prescriptions in the hand-foot-and-mouth disease.

1. Bupleuri and Os Draconis and Concha Ostreae decoction (oral liquid)

In the prescription, the bupleurum, the scutellaria and the pinellia have the effects of relieving fever and calming, and can be used for treating dysphoria, vomiting and the like in the stage 2 nervous system affected stage; os Draconis and Concha Ostreae have tranquilizing effect, and can be used for treating central nervous system injury in stage 2 nervous system affected stage of stage 2 nervous system affected stage, and disturbance of consciousness in stage 4 cardiopulmonary failure stage; the cassia twig, the tuckahoe, the dragon bone and the oyster can enhance the treatment effect of the mental nervous system; the rhubarb can clear away pathogenic heat of liver and gallbladder, dredge intestinal rubbish and viruses and has the functions of diminishing inflammation and easing pain; the ginger, the red date and the radix codonopsitis have the functions of protecting stomach qi and enhancing drug effect.

2. Cutting Bupleurum root, dragon bone and oyster soup (external liquid)

After the decoction, the liquid medicine is taken for external application and irradiated by an infrared lamp. By utilizing the absorption function of skin pores and herpes wounds, rhubarb is used for dredging local garbage, viruses, diminishing inflammation and easing pain, bupleurum, scutellaria and pinellia are used for locally relieving heat and calming and relieving the symptoms of dysphoria and vomiting of the whole body (fullness in chest), and the central nervous system damage symptoms of easy fright, limb shaking, myasthenia, neck rigidity and the like of the whole body are relieved after the dragon bone, oyster, cassia twig and tuckahoe are absorbed through the skin. Radix Aconiti lateralis Preparata is added to enhance therapeutic effect.

3. Bupleuri and Cassia twig decoction (oral liquid)

In the prescription, the bupleurum, the scutellaria and the pinellia have the effects of relieving fever and calming, and can be used for treating dysphoria, vomiting and the like in the stage 2 nervous system affected stage; gui Zhi can relieve exterior syndrome, dispel wind-cold, and Shao Yao can nourish yin and astringe ying, so Gui and Shao are combined to harmonize ying and wei and are reinforced by each other. Ginger, rhizoma Zingiberis recens, being pungent and warm in nature, helps both resolve the muscles and muscles of cinnamon twig and warm the stomach to arrest vomiting. The Chinese dates are sweet and neutral, and can tonify qi, strengthen middle energizer, nourish spleen and promote fluid production. The two herbs for honey-fried licorice root: the first one is an adjuvant drug, which is used for tonifying qi and regulating the middle warmer, and is combined with cassia twig to release muscles, and is combined with peony to benefit yin; the second is a guiding drug to regulate the effects of the other drugs in the recipe.

The invention has the advantages of

1. Bupleuri and Os Draconis and Concha Ostreae decoction (oral liquid)

The prescription is prepared from decoction of Bupleurum tenue, liquorice, dragon's bone, oyster, minium, scutellaria baicalensis, poria cocos and cassia twig, and is mainly used for treating syndromes of marked diffuse shaoyang pathogenic qi, irritability and delirium. Modern doctors are mostly used in the fields of mental nervous system, cardiovascular system, digestive system, gynecology, andrology, dermatology, etc.

The traditional Chinese medicine composition has good curative effects on symptoms of dysphoria, vomiting, central nervous system damage (such as mental retardation, dysphoria, easy fright, vomiting, dysphoria, limb shaking, myasthenia and the like) in the affected stage of the nervous system of the hand-foot-and-mouth disease stage 2, and the like, and has good curative effects on dredging intestinal rubbish and viruses.

2. Cutting Bupleurum root, dragon bone and oyster soup (external liquid)

The formula is added with prepared aconite root on the basis of the decoction of bupleurum root and dragon bone and oyster, changes the dosage and the decoction method, utilizes the absorption function of skin pores and herpes wounds to promote local garbage and virus dredging, diminish inflammation and relieve pain, and relieves and improves the symptoms of dysphoria, vomiting, easy fright, limb shaking, myasthenia, neck rigidity and the like of the whole body.

3. Bupleuri and Cassia twig decoction (oral liquid)

The bupleuri radix and ramulus Cinnamomi decoction is used for treating infantile wind aversion due to exterior deficiency in hand-foot-and-mouth disease, and has antipyretic, antiviral, antiinflammatory, nerve conduction inhibiting, spasmolytic, anticonvulsive, and immunity regulating effects.

The invention firstly uses the bupleurum root, dragon bone and oyster soup and the bupleurum root and cassia twig soup for treating the patients with the hand-foot-and-mouth disease and the sweating at the stage 1 and the stage 2. Experiments show that the invention has obvious advantages in the aspects of healing, significant effect and effective number, and the difference is statistically different. From the specific symptoms, the advantages of the experimental group in three symptoms of rash distribution, food intake reduction and dry mouth and lips have statistical significance; has advantages in drooling, listlessness, dysphoria, easy convulsion, emesis, dysphoria, limb shaking, and myasthenia without statistical difference.

Detailed Description

The clinical data below illustrate the effect of the Chinese medicine in treating hand-foot-and-mouth disease.

In order to verify the treatment effect of the traditional Chinese medicine composition on patients with the hand-foot-and-mouth disease in the stages 1 and 2, clinical tests on children with the hand-foot-and-mouth disease who meet inclusion standards and are diagnosed in the department of medicine in the recovery and career hospital in Tanghe county in Nanyang city of Henan province during the period from 3 months to 12 months in 2018 are performed in a subject group, and the following description is given:

first, diagnosis standard

Clinical diagnosis of cases

1. Incubation period

It is usually 2-10 days, and 3-5 days in average.

2. Signs of clinical symptoms

According to the occurrence and development process of diseases, the hand-foot-and-mouth disease is classified into the following stages:

stage 1-eruption: it is mainly manifested as fever, eruption in the hands, feet, mouth, buttocks, etc., accompanied by cough, watery nasal discharge, and anorexia. Some cases only manifest as rashes or herpangina, and some cases may have no rashes.

Typical rashes are manifested as maculopapules, papules, herpes. The liquid in the inflammatory halation herpes around the rash is less, the pain and the itch are avoided, and the scab and the scar are avoided when the rash is recovered. Atypical skin rashes are usually small, thick, hard, small and sometimes with ecchymosis, ecchymosis. Skin lesions are severe with certain types of enteroviruses such as CV-A6 and CV-A10, and rashes can appear as bullous changes with pain and itching and are not limited to hands, feet, mouth.

Most of the common hand-foot-and-mouth diseases in the period are cured in the period.

Stage 2-nervous system affected stage: in a few cases, central nervous system damage can occur, which mostly occurs within 1-5 days of the course of disease and is manifested as poor spirit, somnolence, weakness in sucking, easy convulsion, headache, vomiting, dysphoria, limb trembling, muscle weakness, neck rigidity, etc.

The severe cases of the hand-foot-and-mouth disease are serious at this stage, and most of the cases can be cured.

Phase 3-pre-cardiopulmonary failure: it is usually occurred within 5 days of the disease course, manifested as increased heart rate and respiration, cold sweating, cold extremities, and blood pressure.

This stage is critical for severe cases of hand-foot-and-mouth disease. Timely identification and correct treatment are the key to reducing the fatality rate.

Stage 4-cardiopulmonary failure stage: this phase can be entered quickly on a phase 3 basis. The clinical manifestations are tachycardia (bradycardia in individual children), tachypnea, cyanosis of the lips, cough with pink foamy sputum or bloody fluid, hypotension or shock. Severe brain failure is also the main manifestation of some cases, with convulsions and severe disturbance of consciousness seen clinically.

The disease belongs to severe and severe hand-foot-and-mouth disease, and the fatality rate is high.

Phase 5-recovery phase: the body temperature is gradually recovered to be normal, the dependence on vasoactive drugs is gradually reduced, the nervous system affected symptoms and the cardio-pulmonary function are gradually recovered, and a few nervous system sequelae can be left. Some cases of hand, foot and mouth (commonly seen in CV-A6 and CV-A10 infected patients) have the symptom of demethylation 2-4 weeks after illness, and new nails grow out in 1-2 months.

The prognosis of most children patients is good, and the children patients can be cured within 1 week generally without sequelae. After a few children suffer from the disease, the nervous system is rapidly affected, the diseases are manifested as brainstem encephalitis, encephalomyelitis, cerebrospinal meningitis and the like, and the death rate of the children suffering from circulatory failure and neurogenic pulmonary edema is high.

(II) confirmed cases

On the basis of clinical diagnosis cases, one of the following cases can be diagnosed.

1. Positive nucleic acid tests specific for enteroviruses (CV-A16, EV-A71, etc.).

2. Enteroviruses were isolated and identified as CV-A16, EV-A71 or other enteroviruses that cause hand-foot-and-mouth disease.

3. And positive acute-phase serum-associated virus IgM antibody.

4. Neutralizing antibodies of serum-associated enteroviruses are increased 4-fold or more in the convalescent phase than in the acute phase.

Second, selection of subjects, exit criteria and grouping

(one) selection criteria (the following 5 conditions should be satisfied simultaneously)

1. The diagnosis standard of confirmed diagnosis cases of hand-foot-and-mouth diseases is met from the hand-foot-and-mouth diagnosis guideline 2018 edition.

2. The symptoms of central nervous system damage in stage 2 nervous system affected stage, such as listlessness, dysphoria, convulsion, emesis, limb trembling, and myasthenia, occur for the first time, and the time for inclusion is less than 36 hr.

3. When the armpit temperature is higher than 37.5 ℃, one or more parts of the palms, the soles, the backs and the like of the children patients have sweating or wet feeling by palpation.

4. Age 2-6 years.

5. The infant patient and the guardian agreed to participate in the experiment and signed an informed consent.

(II) exclusion criteria

1. Before taking part in the experiment, symptoms appear in the early stage of 3-stage cardiopulmonary failure or 4-stage cardiopulmonary failure, and the specific symptoms refer to the hand-foot-mouth diagnosis and treatment guideline 2018 edition.

2. Combined with serious inherited metabolic diseases such as epilepsy, tumor, congenital heart disease, nephropathy, etc.

3. Febrile convulsions.

4. Those who are long-term or currently undergoing hormone therapy for the underlying disease.

5. Are participating in other clinical experimenters.

(III) Exit criteria

The experiment was exited if any of the following events occurred.

1. The infant guardian signs an informed consent, and after the infant guardian is taken into the experiment and receives treatment, symptoms (such as cold sweating, cold extremities, skin flowering, blood pressure increase, bradycardia, tachypnea, cyanosis of lips, pink foam phlegm or bloody liquid, blood pressure reduction or shock and the like) appear in the early stage of 3-stage heart-lung function failure and 4-stage heart-lung failure (see' 2018 edition of hand-foot-mouth diagnosis and treatment guidelines), the infant guardian automatically quits the experiment, treats invalid cases according to treatment and takes effective treatment measures.

2. During the test, allergic reactions or serious adverse events occurred.

3. In the test process, the infant patients suffer from other diseases, which affect the judgment of curative effect and safety.

4. The compliance of the tested children is poor, or the traditional Chinese medicine and western medicine prohibited by the scheme is automatically changed midway or added.

(IV) grouping of children patients

The test group was divided into a control group and an experimental group, each of which was 30 persons. The patients or their guardians sign the informed consent time as the sequence, the single-number arrival persons are classified into the control group, and the double-number arrival persons are classified into the experimental group.

Third, treatment scheme

(one treatment course)

The treatment course is 7 days, and the treatment is finished in case of recovery within 7 days.

(II) basic Care

The children patients are isolated from each other, so that cross infection is avoided. Properly rest, light diet and well care oral cavity and skin. Both the control and experimental groups should suffice.

(III) control group treatment protocol

Referring to the diagnosis and treatment guidelines for hand-foot-and-mouth disease, the specific treatment scheme is as follows:

ribavirin (Zilu pharmaceuticals, Inc.), 10-15 mg/(kg. d)).

For axillary temperature higher than 38.5 deg.C, acetaminophen (Anhui Fengyuan Likang pharmaceutical industry Co., Ltd.) may be added at 10 mg/(kg. times), and the shortest interval time between two administrations is 6 hours.

For patients with dysphoria and limb trembling, mannitol 0.25-1.0 g/(kg) is added, and the injection is administered once every 4-8 hr for 20-30min, and the frequency can be increased to 1 time every 2-4 hr for severe intracranial hypertension or cerebral hernia.

In convulsions, diazepam is added for slow intravenous injection at 0.3-0.5 mg/(kg) times, the maximum dose is not more than 10mg times, and the injection speed is 1-2 mg/min.

(IV) treatment protocol for Experimental group

After getting up in the morning, taking 100ml of oral liquid of the Bupleurum and dragon bone oyster decoction on an empty stomach, and then applying an external application operation (firstly cleaning 15cm around eruption with the external application liquid of the Bupleurum and dragon bone oyster decoction three times, then soaking the Bupleurum and dragon bone oyster decoction, melting, cutting gauze, applying the gauze, and heating for 30min with an infrared physical therapy apparatus (a national kernel infrared physical therapy apparatus, the model is vertical L-1-8A, 9A, and the temperature is slightly hot, and scalding is prevented, which is hereinafter referred to as the external application operation), wherein the slow buccal administration operation is performed during the irradiation period of the infrared physical therapy apparatus (about 50ml of the oral liquid of the Bupleurum and.

Taking 100ml of oral liquid of the Bupleurum and cassia twig decoction two hours after breakfast, and then applying external application.

The oral liquid of Bupleurum root, dragon bone and oyster decoction is taken about 100ml half an hour before lunch, and then the external application operation and the slow buccal administration operation are carried out.

Two hours after lunch, about 100ml of the Bupleurum and Cassia twig decoction is taken and then applied externally.

The oral liquid of Bupleurum and dragon bone and oyster decoction is taken about 100ml half an hour before supper, and then is applied externally and slowly orally.

After two hours after dinner, about 100ml of oral liquid of the bupleurum-cassia twig decoction is taken, and then the external application operation is carried out.

The treatment regimen of the experimental group lasted 7 days.

Fourth, evaluation of safety

(I) safety evaluation index

ALT is used as an index for liver function, Scr is used as an index for kidney function, and the liver function and the kidney function are detected at two time points before and after treatment.

(II) recording and determining adverse events

And setting an Adverse Event (AE) record table, faithfully filling the occurrence time, severity and duration of the AE, the adopted measures and the outcome of the AE, and judging the relationship between the AE and the test medicine.

Fifth, evaluation of effectiveness

Symptom sign grading quantification standard

Referring to the diagnosis and treatment guidelines for common diseases in pediatrics of traditional Chinese medicine and the clinical research guidelines (trial) for new traditional Chinese medicines, the grading and quantification standard of symptoms and signs of the experiment is formed by combining the central nervous system damage manifestations in the clinical manifestation 2 stage (nervous system affected stage) of the hand-foot-and-mouth disease in the diagnosis and treatment guidelines 2018 edition of hand-foot-and-mouth disease, as shown in table 1.

TABLE 1 hierarchical quantification table of symptom and sign

(II) evaluation criteria for therapeutic Effect

The evaluation of the curative effect is carried out by grading and quantifying various symptoms in the table according to symptom signs determined by discussion of subject groups and grading according to a nimodipine method (the calculation formula is (integration before treatment-integration after treatment)/integration before treatment x 100 percent)

1. The clinical cure is as follows: symptoms, signs disappear or essentially disappear, and the syndrome score decreases by > 95%.

2. The medicine has obvious effects of obviously improving symptoms and physical signs and reducing syndrome integration by more than 70 percent.

3. Effective, symptoms and physical signs are all improved, and the syndrome score is less and is more than 30%.

4. The symptoms and physical signs are not obviously improved or even aggravated, and the syndrome score is reduced by less than 30%.

Sixthly, treatment observation point

The experiment is divided into 3 observation points for collecting symptom sign grading quantitative data of the infant, wherein the first observation point is that the guardian of the infant signs an informed consent and is within 2 hours after the infant enters the group; the second observation point was 20 pm on day 3 after receiving treatment with this experiment: 00 later; the third observation point is within 2 hours after the end of the treatment of the experiment.

Adverse events occurred in the experiment, followed every 24 hours until normal or stable.

Seventh, analysis of experimental data

(one) symptom sign overall condition when entering group

When the patients were enrolled, the numbers of normal, light, medium and heavy patients were counted for each symptom in the control group and the experimental group as shown in the following table.

TABLE 2 statistical tables of symptom rest at group entry

The control group and the experimental group have fever, rash distribution and myasthenia through Fisher chi-square test, and other symptoms through Pearson chi-square test, and the P is more than 0.05, and no statistical difference exists.

(II) treatment of symptoms after 3 days

TABLE 3 statistical Table of symptom rest at 3 days after treatment

The data in the table were examined using the Fisher chi-square test.

Wherein, the symptoms P of fever and food intake reduction is less than 0.05, and the difference has statistical significance. The number of the control group with normal body temperature, mild fever, moderate fever and severe fever is 14, 9, 7 and 0 respectively, while the number of the experimental groups with 4, 15, 10 and 1 respectively indicate that the temperature reduction effect of the experimental group is poor after 3 days of treatment.

The number of people with normal, mild, moderate and severe food intake of the control group is 3, 16, 10 and 2 respectively, and the number of people of the experimental group is 13, 8, 9 and 0 respectively, which shows that the experimental group has advantages in improving diet after 3 days of treatment.

(III) sign of symptoms after the end of treatment

TABLE 4 statistical tables of symptom rest at the end of treatment

The data in the table were examined using the Fisher chi-square test. Wherein the three symptoms of rash distribution, food intake reduction and dry mouth and lips P is less than 0.05, and the difference has statistical significance.

The number of normal, light, medium and heavy people in the control group and the number of people in the experimental group are respectively 3, 19, 8 and 0, and the number of people in the experimental group is respectively 12, 8, 10 and 0, which shows that the experimental group has the advantage of improving the rash.

The number of normal, light, medium and heavy people with decreased food intake in the control group was 7, 15, 8 and 0 respectively, and the number of people in the experimental group was 18, 8, 4 and 0 respectively, indicating that the experimental group had an advantage in improving food intake.

The number of normal, light, medium and heavy people in the control group with dry lips is 9, 16, 4 and 1 respectively, and the number of people in the experimental group is 20, 6, 4 and 0 respectively, which shows that the experimental group has the advantage of improving the food intake.

(IV) evaluation of therapeutic Effect

TABLE 5 statistical table of the therapeutic effects at the end of the treatment

The data in the table were tested using Fisher chi-square test, where P0.047 <0.05 indicates that the control and experimental groups were statistically significant in terms of difference in therapeutic effect. The experimental group has advantages in terms of the number of healed people and the number of effective people.

Eight, conclusion

(one) therapeutic effect

From the specific symptoms, the experimental group has advantages in three symptoms of rash distribution, food intake reduction and dry mouth and lips, and the difference has statistical significance; has advantages in drooling, listlessness, dysphoria, easy convulsion, emesis, dysphoria, limb shaking, and myasthenia without statistical difference.

On the whole, the experimental group has advantages in recovery, effect and effective number, and the difference has statistical significance.

(II) evaluation of safety

In the experiment, the ALT and Scr indexes of the children are normal without adverse events.

Typical cases

Clinical case 1:

the rest, 5 years old, 5 months old, to national town of Tanghe county, 2017, and 5 months old, to national hospital of Tanghe county, the temperature of the next day heating body reaches 39.1 deg.C, and the temperature is reduced to 37.8 deg.C after ibuprofen suspension is orally administered; herpes appears on hands and feet at the 3 rd day, the body temperature is near 39 ℃, nasal discharge and anorexia occur, and the doctor visits the hospital at about 3 pm.

When the patient comes to the clinic, the patient cries and scrues more slowly, the mental state is poor, the physical examination shows that the muscle strength is reduced, and the body temperature is 38.7 ℃. Slight sweating occurred in the palms and backs. Laboratory examination: EV-A71 virus was isolated from the intestinal tract.

Orally taking the decoction of Bupleurum root, dragon bone and oyster shell and the decoction of Bupleurum root, cassia twig and the like, and cleaning the eruption part by using the decoction of Bupleurum root, dragon bone and oyster shell which is cut into external application liquid medicine. The specific treatment protocol is detailed in the section "treatment protocol of experimental group".

After 3 days of treatment, the body temperature is 37.8 ℃, but the mental state is good, the children can be played in hospital in non-treatment period, the diet is basically normal, and the hand herpes expands after being externally applied, but the children do not feel pain when touching.

After 7 days of treatment, the temperature was normal and the herpes resolved before discharge.

Clinical case 2:

zhao, 4 years old, Tang river county Qijiu county, Nanyang city, 6 Yue 8 in 2018. Parent and parent complaints: the children suffer from fever at 38.6 ℃ yesterday and cough, and have fever reduction after being given small radix bupleuri granules and children cough syrup; fever again this day, body temperature 38.9 ℃. As the children's kindergarten has stopped learning due to hand-foot-and-mouth disease, the children are in the hospital to see a doctor.

Body examination finds herpes and swelling of oral pharynx and isthmus, hands and buttocks, and has a small amount of liquid therein. The infant suffered from bad mental state, continuous crying, cough and salivation, and the mother reported bad appetite, vomiting 3 times in the morning and evening. Physical examination and display: sweats in the palms and backs, body temperature 38.6 ℃. Laboratory examination: EV-A71 virus was isolated from the intestinal tract.

After 3 days of treatment, the body temperature is 37.5 ℃, the red swelling of the herps in the isthmus is reduced, the mental state is correct, the cough is relieved, the appetite is correct, and vomiting is avoided.

After 7 days of treatment, the body temperature was normal and the angina was discharged after the disappearance of the herpes.

The clinical cases show that the bupleuri radix, the dragon bone and the oyster soup and the sanction thereof and the bupleurum-cassia twig soup can effectively treat the sweating type hand-foot-and-mouth disease types in the stages 1 and 2, provide a new clinical treatment scheme for treating the sweating type hand-foot-and-mouth disease, and have important medical significance.

Claims

1. Application of bupleuri radix, Os Draconis and Concha Ostreae decoction in preparing medicine for treating sweating type hand-foot-and-mouth disease of stage 1 and stage 2 is provided.

2. The use of claim 1, wherein the decoction is prepared from a Chinese medicinal composition comprising Bupleurum 60-125g, Codonopsis pilosula 20-45g, Poria cocos 20-45g, Os Draconis 20-45g, oyster 20-45g, Cinnamomum cassia 20-45g, Magnetitum 20-45g, radix Scutellariae 20-45g, pinellia ternata 20-100g, rhubarb horsetails 30-60g, ginger 20-45g, and torn Zizyphi fructus 6-12;

preferably, the decoction is prepared from a traditional Chinese medicine composition comprising 60g of radix bupleuri, 20g of codonopsis pilosula, 20g of poria cocos, 20g of dragon bone, 20g of oyster, 20g of cinnamon, 20g of magnetite, 20g of raw scutellaria baicalensis, 20g of ginger processed pinellia, 30g of raw rhubarb, 20g of cut ginger and 6 torn jujubes.

3. The use of claim 1, wherein the medicament further comprises a decoction of radix bupleuri, Os Draconis and Concha Ostreae, wherein the decoction of radix bupleuri, Os Draconis and Concha Ostreae is prepared from a Chinese medicinal composition comprising 60-125g of radix bupleuri, 20-45g of radix Codonopsis, 20-45g of Poria, 20-45g of Os Draconis, 20-45g of Concha Ostreae, 20-45g of cortex Cinnamomi, 20-45g of Magnetitum, Haematitum, lapis Micae aureus, or pulvis Ferri, 20-45g of radix Scutellariae, 20-100g of rhizoma Pinelliae Preparada, 30-60g of radix et rhizoma Rhei, 20-45g of cut rhizoma Zingiberis recens, 6-12 torn fructus Jujubae, and 15-30g of radix Aconiti lateralis Preparata;

preferably, the decoction of radix bupleuri, dragon bone and oyster is prepared from a traditional Chinese medicine composition comprising 125g of radix bupleuri, 45g of codonopsis pilosula, 45g of poria cocos, 45g of dragon bone, 45g of oyster, 45g of cinnamon, 45g of magnetite, 45g of raw scutellaria baicalensis, 60g of prepared pinellia ternate, 60g of raw rhubarb, 45g of cut ginger, 12 torn jujubes and 30g of prepared monkshood.

4. The use as claimed in claim 3, wherein the decoction of Bupleurum and Os Draconis Concha Ostreae is used as external preparation.

5. The use of any one of claims 1 to 4, wherein the medicament further comprises CHAIHUGUIZHI decoction.

6. The use of claim 5, wherein the chaihu guizhi decoction is prepared from a Chinese medicinal composition comprising 60-125g of chaihu, 20-45g of prepared pinellia tuber, 20-45g of dangshen, 20-45g of raw scutellaria baicalensis, 15-30g of prepared licorice, 20-45g of cassia twig, 20-45g of white peony root, 20-45g of cut ginger and 6-12 torn jujubes;

preferably, the bupleurum-cassia twig decoction is prepared from a traditional Chinese medicine composition comprising 60g of bupleurum, 20g of prepared pinellia, 20g of codonopsis pilosula, 20g of raw scutellaria baicalensis, 20g of honey-fried licorice root, 20g of cassia twig, 20g of white paeony root, 20g of cut ginger and 6 torn jujubes.

7. Application of bupleuri radix and ramulus Cinnamomi decoction in preparing medicine for treating sweating type hand-foot-and-mouth disease of stage 1 and stage 2; wherein, the bupleurum-cassia twig decoction is prepared by a traditional Chinese medicine composition which comprises 60-125g of bupleurum, 20-45g of prepared pinellia, 20-45g of codonopsis pilosula, 20-45g of raw scutellaria baicalensis, 15-30g of honey-fried licorice root, 20-45g of cassia twig, 20-45g of white paeony root, 20-45g of cut ginger and 6-12 torn jujubes;

the bupleurum-cassia twig decoction is prepared from 60g of bupleurum, 20g of prepared pinellia, 20g of codonopsis pilosula, 20g of raw scutellaria baicalensis, 20g of honey-fried licorice root, 20g of cassia twig, 20g of white paeony root, 20g of cut ginger and 6 torn jujubes.

8. The application of the decoction of radix bupleuri, dragon bone and oyster in preparing the medicine for treating the sweating type hand-foot-and-mouth disease in the stages 1 and 2 is characterized in that the decoction of radix bupleuri, dragon bone and oyster is prepared from 60-125g of radix bupleuri, 20-45g of codonopsis pilosula, 20-45g of poria cocos, 20-45g of dragon bone, 20-45g of oyster, 20-45g of cinnamon, 20-45g of magnetite, ruddle, chlorite schist, or ferrite, 20-45g of raw scutellaria baicalensis, 20-100g of prepared pinellia ternate, 30-60g of raw rhubarb, 20-45g of cut ginger, 6-12 torn jujubes and 15-30g of prepared monkshood;

9. The use of claim 8, wherein the decoction of Bupleurum and Ostrea draconis is used as an external preparation.