CN114470110B

CN114470110B - Anti-rhinitis traditional Chinese medicine composition with pain relieving effect

Info

Publication number: CN114470110B
Application number: CN202210346820.0A
Authority: CN
Inventors: 沃万珑
Original assignee: Zhejiang Chinese Medicine University ZCMU
Current assignee: Zhejiang Chinese Medicine University ZCMU
Priority date: 2022-03-31
Filing date: 2022-03-31
Publication date: 2023-12-19
Anticipated expiration: 2042-03-31
Also published as: CN114470110A

Abstract

The invention discloses an anti-rhinitis traditional Chinese medicine composition, which comprises the following traditional Chinese medicine raw materials: the total amount of the baikal skullcap root, the rhizome of chuanxiong, the magnolia flower, the angelica dahurica, the succus bambusae, the grassleaf sweelflag rhizome, the fritillaria thunbergii, the platycodon grandiflorum, the poria cocos, the agastache rugosus and the peppermint is 2-4 times of the amount of the succus ligustici chuanxiong, and the total amount of the baikal skullcap root and the rhizome of chuanxiong is preferably 3 times of the amount of the succus bambusae. The anti-rhinitis traditional Chinese medicine composition provided by the invention has reasonable compatibility design, scientific administration of monarch, minister, assistant and guide, single and definite treatment purpose, and creatively uses the bamboo juice as ministerial drug and the monarch drug containing the baikal skullcap root-ligusticum wallichii drug pair for use, thereby achieving the unexpected treatment effect of synergizing the monarch drug and relieving pain; in addition, the prescription provided by the invention can also effectively treat allergic rhinitis, lighten the irritation of the medicine to rhinitis patients, and has great clinical application value and market development potential.

Description

Anti-rhinitis traditional Chinese medicine composition with pain relieving effect

Technical Field

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to an anti-rhinitis traditional Chinese medicine composition with an analgesic effect, which has a very strong analgesic effect particularly aiming at the nasal cavity irritation of patients with wind-heat rhinitis.

Background

Rhinitis is a nasal mucosal inflammation caused by bacteria, viruses, allergens, etc. In recent years, the incidence rate of rhinitis in China is up to 37%, the number of patients is gradually increased by 3% each year, the younger trend of rhinitis patients is also more obvious, and teenager rhinitis patients account for 2/3 of the rhinitis population. Rhinitis patients are classified according to disease types, and can be classified into allergic rhinitis (AR, also called as "allergic rhinitis") patients and non-allergic rhinitis patients, wherein allergic rhinitis is the most common chronic inflammatory diseases of respiratory tract in patients, the quality of life of patients is seriously affected, and a large disease burden is caused.

Allergic rhinitis (allergic rhinitis, AR) is a type i allergic reaction, an immunoglobulin E (IgE) mediated by an allergen, a non-infectious chronic inflammatory disease of the nasal mucosa, with clinically typical nasal symptoms of sneezing, watery nasal discharge, nasal itching, nasal congestion, etc., other significant non-nasal symptoms generally including itching eyes, tears, redness of eyes, ears and/or upper jaw itching. The clinical Allergic Rhinitis (AR) can be classified into seasonal AR (seasonal allergic rhinitis, SAR) and perennial AR (perennial allergic rhinitis, PAR) (Yao Hezhi, li Rui, cao Weiyi, yang Qiaoning, high stamen, new clinical research scheme design of allergic rhinitis traditional Chinese medicine (J), J.China J.New medicine, 2020, (29) 5:520-524.).

The existing treatments for Allergic Rhinitis (AR) comprise treatment methods such as operation treatment, desensitization treatment, drug treatment and the like, and the operation treatment has high cost, poor effect and more sequelae, and can possibly cause dry atrophic rhinitis. Desensitization therapy can radically treat allergic rhinitis, but requires that the patient be simple allergic rhinitis and that corresponding allergen vaccines be present, but the therapy is limited in that: (1) the recorded allergens are more than 2 ten thousand, and the specific patients need to be searched for symptomatic allergens when carrying out immunotherapy, just like a sea fishing needle; (2) the same person is often allergic to a plurality of substances, so that the finding of a plurality of symptomatic allergens is more difficult; (3) either all allergens can be desensitized, such as dust mites, ultraviolet allergies, or substances that are not desensitized; (4) desensitization therapy itself has the problems of long period, slow onset of action, large side effects, easy initiation of systemic or local adverse reactions, etc., so patients are generally difficult to adhere to. (Li Yingshuai, wang Ji, li Lingru, zhang Huimin, zheng Yanfei, yang Yin, wang Qi, etc.. Theoretical construction of allergic constitution [ Z ]. Infinite evidence study, academy of Chinese medicine, 2013 academy of sciences, 2014: 91-92.)

Regarding the therapeutic drugs for allergic rhinitis, western medicine therapy, traditional Chinese medicine therapy and combined therapy of traditional Chinese medicine and western medicine therapy exist at present, but are not satisfactory. The relevant literature for AR therapeutics is searched as follows:

For example, the ranolazine nasal spray is used as a glucocorticoid medicine, is a first-line medicine recommended by the American AR diagnosis and treatment guide for treating moderate-severe AR, has the advantages of quick response and safe application, and can also effectively improve the sleep quality of AR patients. However, it is disadvantageous in that: the drug is easy to relapse and difficult to radically cure after stopping the drug, the course of allergic reaction cannot be changed, individual treatment cannot be realized aiming at single symptoms, and the treatment period is longer; a significant proportion of AR patients are not satisfied with the results of drug treatment (Gu Yifan, chen, wen Zhihong, xie Qi, zhao Jiping. Influence of Raynaud's combined therapy with separate therapy on clinical symptoms and sleep quality in patients with persistent moderate to severe allergic rhinitis [ J. ]. Needle stick studies, 2020,45 (1): 46-50.).

For example, olopatadine hydrochloride nasal sprays (olopatadine hydrochloride, sold under the trade name Patanase) marketed by the U.S. FDA are histamine H1 receptor inhibitors useful for the treatment of seasonal allergic rhinitis in adults and children over 6 years of age, and no clinical research literature has been reported to provide nasal analgesia. In addition, the researches of scholars such as the Chinese zodiac science and the like show that the common (> 1%) adverse reactions of the medicine comprise bitter taste (12.8%), headache (4.4%), nosebleed (3.2%), sore throat (2.2%), post-nasal drip (1.5%), and the like (Chinese zodiac science, he Yuan. The pharmaceutical research of novel antiallergic drug olopatadine hydrochloride nasal spray [ J ]. North pharmacy, 2016,13 (2): 163-164), and the medicine has larger irritation to nasal mucosa, more side effects and easiness in causing nasal pain.

For example, fang Xiaoqun et al, using a combination of Magnolia Siberian cocklebur fruit powder (containing Chinese herbal medicines such as Magnolia flower, xanthium sibiricum, ledebouriella root, etc.) and cetirizine for treating allergic rhinitis, show that the variation of total IgE before and after treatment of the combination group (administration of Magnolia Siberian cocklebur fruit powder + cetirizine) is statistically significant (P < 0.01), and the variation of the control group (administration of cetirizine) is not significant, showing that oral administration of Magnolia Siberian cocklebur fruit powder + cetirizine for treating allergic rhinitis can significantly alleviate clinical symptoms (Fang Xiaoqun, an Li, liu. The combination of Magnolia Siberian and cetirizine for treating allergic rhinitis clinical observation [ J ]. Sub-traditional medicine, 2010,6 (6): 44-45.). However, it is disadvantageous in that: the potential risk of adverse reactions of viscera such as digestive system injury caused by oral administration of fructus Xanthii caused by the irritation reaction to nasal cavity after administration of rhinitis patients is not considered.

For example, chinese patent No. CN110013507A discloses a traditional Chinese medicine composition for treating mixed rhinitis, which is prepared from the following raw materials in parts by weight: 15-40 parts of dandelion, 15-30 parts of houttuynia cordata, 6-15 parts of radix scutellariae, 10-30 parts of selfheal, 8-20 parts of ligusticum wallichii, 8-15 parts of schizonepeta, 10-20 parts of radix sileris, 10-20 parts of radix angelicae, 6-12 parts of peppermint, 3-5 parts of liquorice, 5-10 parts of platycodon grandiflorum, 6-15 parts of light cocklebur, 10-15 parts of magnolia flower, 10-20 parts of rhodiola rosea, 10-15 parts of radix bupleuri, 6-15 parts of bird-plums, 6-15 parts of vinegar schisandra chinensis and 20-50 parts of raw oyster. The traditional Chinese medicine composition can be used for treating the mixed rhinitis of allergic rhinitis accompanied by turbinate hypertrophy, but the technical scheme of the patent is that: the irritation response to nasal cavity after taking medicine is not considered, and the pain relieving effect is weak.

The AR therapeutic drugs related to the aforementioned documents have the following common disadvantages: (1) in the treatment of allergic rhinitis, the influence of the irritation of the drug on the patient, in particular the pain and discomfort in the nasal cavity of the patient, is not considered; (2) some medicines have obvious adverse reactions, such as viscera injury of digestive system, nasal mucosa ulcer, angioedema, etc.

From the therapeutic theory of traditional Chinese medicine, wind-heat in lung meridian can also cause allergic rhinitis, also called "nasosinusitis". The clinical manifestations of rhinitis due to wind-heat are yellow nose, dizziness and pain, dry mouth and tongue, thin and yellow coating, and wiry and rapid pulse. Clinical studies show that the onset of allergic rhinitis is mostly accompanied with symptoms such as nasal cavity pain, dysphagia and the like; nasal pain is caused by nasal mucosa lacerations, glossopharyngeal nerves and vagus nerves stimulated, and particularly inflammatory cells exude, which sensitizes nerve end-pin receptors, releasing pain causing substances, thereby causing local pain sensation, which is particularly pronounced when swallowing. In this way, many rhinitis patients are denied food intake due to pain, thereby affecting nutrient intake and being unfavorable for patient rehabilitation (Wang Ying, analysis of the effect of swallowing surface electromyography to evaluate the pain degree of perennial allergic rhinitis patients [ J ]. Ind. Medical college, 2017,32 (1): 109-111.).

Unfortunately, in general, in the traditional Chinese medicine treatment, all the prescriptions are focused on dispelling wind and relieving stuffy nose, and are mainly used for treating wind-heat rhinitis and difficult to treat nasal pain at the same time.

The rhinitis spray of flos Magnoliae prepared by the improved process of Li Yingchun, which is composed of herba Ephedrae, flos Magnoliae, herba asari, cortex Phellodendri, borneolum Syntheticum, etc., can treat various symptoms such as acute rhinitis, chronic rhinitis, allergic rhinitis and sinusitis, and has remarkable curative effect; however, the technical scheme has the following defects: herba asari can be used for relieving pain and cough, but has obvious toxic and side effects, and the dosage of the medicine should be strictly controlled (Li Yingchun. Preclinical study of the spray for rhinitis in flos Magnoliae [ D ]. Guangdong college of pharmacy, 2011.).

The Chinese patent No. CN110403999A discloses a traditional Chinese medicine composition for treating allergic rhinitis, which comprises the following components in parts by weight: 10-20 parts of magnolia flower, 15-20 parts of liquorice, 5-15 parts of raspberry, 15-20 parts of pseudo-ginseng, 5-10 parts of radix angelicae, 10-23 parts of selfheal, 9-18 parts of centipeda, 7-16 parts of dandelion, 8-13 parts of mint, 6-9 parts of schisandra chinensis and 4-9 parts of cocklebur fruit. But the formula is characterized in that: flos Magnoliae, radix Angelicae Dahuricae, fructus Xanthii, herba Centipedae, and herba Centipedae, which can dispel wind-cold and relieve stuffy nose; spica Prunellae and herba Taraxaci have effects of clearing pathogenic fire, relieving pain, resolving hard mass and detumescence. However, the disadvantage of this formulation is that: fructus Xanthii is used in the formula, and the adverse reaction hidden trouble that viscera are easily damaged is caused by oral administration.

For example, chinese patent No. CN1682859A discloses a traditional Chinese medicine for treating rhinitis, which comprises the following components: 30 g of fructus xanthil, 30 g of flos magnoliae, 6 g of ephedra, 4 g of asarum, 4 g of peppermint, 15 g of astragalus, 15 g of phellodendron, 15 g of rheum officinale, 6 g of negundo chastetree fruit juice, 16 g of bamboo juice and 0.1 g of musk. The formula is characterized in that: fructus Xanthii is used as a monarch, herba Ephedrae, fructus Viticis negundo juice and succus Bambusae are used as ministerials, flos Magnoliae, herba asari, herba Menthae and Moschus are used as assistants, and radix astragali, cortex Phellodendri and radix et rhizoma Rhei are used as guides, so that the effects of removing dampness, relieving pain, dredging orifice, dispelling wind and dredging collaterals, and clearing heat and detoxicating are achieved. Wherein fructus Viticis negundo juice has effects of dispelling pathogenic wind, eliminating phlegm, activating qi-flowing, and relieving pain, and succus Bambusae has effects of clearing heat and eliminating phlegm. However, the disadvantage of this formulation is that: the formula adopts fructus Xanthii and herba asari with larger dosage, has hidden danger of toxic and side effects, and needs to strictly control the safety of the medicine.

For example, chinese patent No. CN111643614A discloses a traditional Chinese medicine composition for treating rhinitis, which comprises the following traditional Chinese medicines in parts by mass: 10 to 40 parts of coix seed, 10 to 40 parts of wrinkled gianthyssop herb, 10 to 40 parts of plantain herb, 10 to 40 parts of peppermint, 3 to 12 parts of safflower, 10 to 40 parts of chrysanthemum, 10 to 40 parts of cordate houttuynia, 3 to 12 parts of szechuan lovage rhizome, 10 to 40 parts of baical skullcap root, 3 to 12 parts of cassia twig, 5 to 20 parts of lophatherum gracile and 0.05 to 0.2 part of borneol. The formula is characterized in that: semen Coicis and herba Agastaches are monarch drugs for clearing spleen and stomach damp-heat, eliminating dampness with aromatics, removing nasal discharge and inducing resuscitation; herba plantaginis and radix Scutellariae are used for clearing heat and detoxicating; herba Houttuyniae has effects of promoting diuresis and expelling pus as ministerial drugs; flos Chrysanthemi and herba Menthae are effective in removing heat, improving eyesight, inducing resuscitation, and relieving pain; ligusticum wallichii, safflower, cassia twig and borneol have the effects of promoting blood circulation to arrest pain, freeing nasal orifices, and making monarch drug cool and cool as adjuvant drug, lophatherum gracile She Gandan has the effects of clearing heat and promoting diuresis, so that damp-heat in spleen and stomach of middle-jiao is discharged from lower jiao as guiding drug. The combination of the medicines has the effects of clearing heat and promoting diuresis, removing nasal discharge and inducing resuscitation. The embodiment of the specification of the patent shows that the formula has better analgesic, anti-inflammatory and detumescence effects.

In summary, in the existing anti-rhinitis traditional Chinese medicine composition, bamboo juice is mostly used for clearing heat and resolving phlegm, but no literature report exists that the bamboo juice can be used as ministerial medicine for treating nasal pain accompanied by allergic rhinitis by combining with scutellaria baicalensis and ligusticum wallichii.

Therefore, the selection of a proper traditional Chinese medicine composition has the nasal cavity pain relieving effect while treating allergic rhinitis, and is a technical problem which is not solved by the person skilled in the art.

Disclosure of Invention

The invention aims to solve the technical problem of providing an anti-rhinitis traditional Chinese medicine composition with an analgesic effect, wherein the composition contains a plurality of traditional Chinese medicines such as baical skullcap root, szechuan lovage rhizome and bamboo juice, so as to realize the dual effects of treating nasal cavity pain and allergic rhinitis.

In order to achieve the aim of the invention, the invention adopts the following technical scheme:

an anti-rhinitis traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials: radix scutellariae, ligusticum wallichii, magnolia flower, radix angelicae, succus bambusae, rhizoma acori graminei, fritillaria thunbergii, platycodon grandiflorum, poria cocos, wrinkled gianthyssop and mint, wherein the sum of the dosage of the radix scutellariae and the ligusticum wallichii is 2-4 times of the dosage of the succus bambusae.

Preferably, in the traditional Chinese medicine raw materials, the components and the dosages thereof are as follows in parts by mass: 20-25 parts of baical skullcap root, 20-30 parts of szechuan lovage rhizome, 15-30 parts of magnolia flower, 10-20 parts of dahurian angelica root, 15-18 parts of bamboo juice, 20-30 parts of grassleaf sweelflag rhizome, 20-30 parts of thunberg fritillary bulb, 20-40 parts of platycodon root, 20-30 parts of Indian buead, 25-30 parts of wrinkled gianthyssop herb and 10-30 parts of peppermint.

Preferably, the total amount of the baikal skullcap root and the chuanxiong rhizome is 3 times of the amount of the bamboo juice in the traditional Chinese medicine raw materials by mass parts.

More preferably, in the traditional Chinese medicine raw materials, the components and the dosage thereof are as follows in parts by mass: 24 parts of baical skullcap root, 24 parts of szechuan lovage rhizome, 20 parts of magnolia flower, 15 parts of dahurian angelica root, 16 parts of bamboo juice, 27 parts of grassleaf sweelflag rhizome, 25 parts of thunberg fritillary bulb, 29 parts of platycodon root, 25 parts of Indian buead, 26 parts of wrinkled gianthyssop herb and 19 parts of mint.

Preferably, the traditional Chinese medicine composition further comprises auxiliary materials, and the auxiliary materials comprise preservatives. In the present invention, the preservative is at least one pharmaceutically acceptable common auxiliary material, including but not limited to ethyl hydroxybenzoate, methyl hydroxybenzoate, propyl hydroxybenzoate, sodium benzoate, potassium benzoate, benzoic acid, benzalkonium bromide, benzalkonium chloride, chlorobutanol, chlorhexidine acetate, and the like.

Preferably, the formulation of the aforementioned Chinese medicinal composition is a nasal delivery system, including nasal liquid preparation, nasal semisolid preparation or nasal solid preparation.

More preferably, when the aforementioned Chinese medicinal composition is a nasal liquid preparation, the dosage form may be selected from any one of nasal drops, nasal washes, and nasal sprays; when the above-mentioned Chinese medicinal composition is semi-solid preparation for nose, the dosage form can be selected from any one of nasal ointment, nasal cream and nasal gel; when the above-mentioned Chinese medicinal composition is a nasal solid preparation, the dosage form may be selected from any one of nasal powder, nasal powder spray and nasal stick.

The invention also provides application of the anti-rhinitis traditional Chinese medicine composition in preparation of a medicine for treating wind-heat rhinitis.

Preferably, the medicament for treating the wind-heat rhinitis can also treat nasal cavity pain complicated with the wind-heat rhinitis.

Aiming at the traditional Chinese medicine composition with the effects of treating allergic rhinitis and nasal pain, the invention also provides a preparation form of a nasal spray, wherein each 1000mL of the preparation comprises the following traditional Chinese medicine raw materials in parts by weight: 240 parts of baical skullcap root, 240 parts of szechuan lovage rhizome, 200 parts of magnolia flower, 150 parts of dahurian angelica root, 160 parts of bamboo juice, 270 parts of grassleaf sweelflag rhizome, 250 parts of thunberg fritillary bulb, 290 parts of platycodon root, 250 parts of Indian buead, 260 parts of wrinkled gianthyssop herb and 190 parts of mint.

Preferably, when the traditional Chinese medicine composition is used as a nasal spray, each 1000mL of the preparation comprises the following components in parts by weight: 240g of baical skullcap root, 240g of szechuan lovage rhizome, 200g of magnolia flower, 150g of dahurian angelica root, 160g of bamboo juice, 270g of grassleaf sweelflag rhizome, 250g of thunberg fritillary bulb, 290g of platycodon root, 250g of Indian buead, 260g of wrinkled gianthyssop herb and 190g of mint, and 0.2-0.5 g of preservative.

Furthermore, the invention also provides a preparation method of the nasal spray, which comprises the following specific steps (corresponding extraction process flow is shown in figure 1):

1) Weighing each plant medicine according to the prescription, cleaning, crushing and mixing the plant medicine, adding water with the mass of 5 times, and performing ultrasonic extraction to obtain concentrated liquid medicine;

2) Adding 70% ethanol into the concentrated liquid medicine obtained in the step 1) for alcohol precipitation, and standing for the first time to obtain a supernatant (1); continuously adding 45% ethanol into the rest precipitation solution, and standing for the second time to obtain a supernatant (2);

3) Recovering ethanol from the supernatant (1) and the supernatant (2) obtained in the step (2), refining the liquid medicine (decolorizing with active carbon for 2 h), adding auxiliary materials with prescription amount after refining, and adjusting the volume of the liquid medicine to 1000ml to obtain a semi-finished product;

4) And (5) after the semi-finished product is inspected to be qualified, sterilizing and filling to obtain a finished product.

In the invention, the efficacy of each traditional Chinese medicine specified in the common general knowledge of Chinese pharmacopoeia (2020 edition), local traditional Chinese medicine standards and the like is as follows:

radix Scutellariae Baicalensis: [ the nature enters meridians ]. It enters lung, gallbladder, spleen, large intestine and small intestine meridians. [ functional indications ] clear heat and dry dampness, purge fire and detoxify, stop bleeding, and prevent abortion. Can be used for treating damp-heat, summer-heat, chest distress, emesis, damp-heat distention and fullness, dysentery, jaundice, cough due to lung heat, polydipsia due to high fever, hematemesis, epistaxis, carbuncle, swelling, sore, and fetal movement.

Ligusticum wallichii: [ the nature enters meridians ] pungent and warm. Enter liver, gallbladder and pericardium meridians. [ functional indications ] activate blood and promote qi circulation, expel wind and alleviate pain. Can be used for treating chest pain, hypochondrium pain, traumatic injury, menoxenia, amenorrhea, dysmenorrhea, abdominal pain, headache, and rheumatalgia.

Flos Magnoliae: [ the nature enters meridians ] pungent and warm. Enter lung and stomach meridians. [ functional indications ] dispel wind-cold, unblock the orifices of the nose. Can be used for treating headache due to wind-cold, nasal discharge, allergic rhinitis, and nasosinusitis.

Radix angelicae: [ the nature enters meridians ] pungent and warm. Enter stomach, large intestine and lung meridian. [ functional indications ] relieve exterior syndrome, dispel cold, dispel wind, alleviate pain, free nose, dry dampness, stop leukorrhagia, reduce swelling and expel pus. Can be used for treating common cold, headache, glabellar bone pain, nasal obstruction, nasal discharge, allergic rhinitis, nasosinusitis, toothache, leukorrhagia, and pyocutaneous disease.

Bamboo juice: [ the nature and flavor enter meridians ]. Enters the heart and stomach meridians. [ functional indications ] clear heat and resolve phlegm. Can be used for treating apoplexy due to phlegm stagnation, lung heat, asthma, cough, fever and dysphoria.

Rhizoma Acori Graminei: [ the nature enters meridians ], is pungent and bitter and warm. It enters heart and stomach meridians. [ Functions ] induce resuscitation, eliminate phlegm, refresh mind, improve intelligence, resolve dampness and promote appetite. Can be used for treating unconsciousness, epilepsy, amnesia, insomnia, tinnitus, deafness, gastric distention, hunger, and dysentery.

Thunberg fritillary bulb: [ the nature and flavor enter meridians ] is cold and bitter, enters lung and heart meridians. [ functional indications ] clear heat, resolve phlegm, relieve cough, detoxify, resolve stasis and cure carbuncles. Can be used for treating cough due to wind-heat, phlegm-fire, pulmonary abscess, acute mastitis, scrofula, and skin sore.

Radix Platycodi: [ the nature enters meridians ], is bitter and pungent, and is Ping. Enter lung meridian. [ functional indications ] ventilating the lung, relieving sore throat, eliminating phlegm, and expelling pus. Can be used for treating cough with excessive phlegm, chest distress, pharyngalgia, hoarseness, pulmonary abscess, and pus discharge.

Poria cocos: [ the nature enters meridians ], sweet and bland, and Ping. It enters heart, lung, spleen and kidney meridians. [ functional indications ] induce diuresis, excrete dampness, invigorate the spleen and calm the heart. Can be used for treating edema, oliguria, phlegm retention, palpitation, spleen deficiency, anorexia, loose stool, diarrhea, uneasiness, palpitation, and insomnia.

Wrinkled giant hyssop: [ the nature enters meridians ]. Enters spleen, stomach and lung meridians. [ Functive indications ] dispel summer-heat, relieve exterior syndrome, dispel dampness and harmonize stomach. Can be used for treating summer-heat and damp type common cold, chest distress, abdominal pain, emesis and diarrhea.

Peppermint: [ the nature enters meridians ] pungent and cool. It enters lung and liver meridians. [ FUNCTIONAL APPLICABILITY ] dispelling wind-heat, clearing head and eyes, relieving sore throat, promoting eruption, soothing liver and activating qi-flowing. Can be used for treating wind-heat type common cold, initial wind-warm syndrome, headache, conjunctival congestion, pharyngitis, aphtha, rubella, measles, chest distress and hypochondrium distention.

Bamboo shavings: [ the nature and flavor enter meridians ]. It enters lung, stomach, heart and gallbladder meridians. [ functional indications ] clear heat and resolve phlegm, relieve dysphoria and arrest vomiting. Can be used for treating cough due to phlegm heat, excessive internal heat, phlegm, palpitation, restlessness, insomnia, apoplexy, phlegm, aphasia, emesis due to stomach heat, vomiting of pregnancy, and fetal movement.

The traditional Chinese medicine composition provided by the invention has reasonable design of formula compatibility, scientific administration of monarch, minister, assistant and guide, obvious effects of relieving pain and treating wind-heat rhinitis, and the principle of the formula compatibility is as follows:

The principal drug is 4 drugs (two groups are paired): the radix Scutellariae and rhizoma Chuanxiong are paired, and have effects of clearing away heat and toxic materials, activating qi-flowing, relieving pain, and purging pathogenic fire, and can be used for treating nasal cavity pain due to wind-heat type rhinitis; and flos Magnoliae and radix Angelicae Dahuricae, has effects of dispelling pathogenic wind and relieving stuffy nose, and can be used for treating wind-heat type rhinitis.

The ministerial drugs are 4 kinds of drugs: the bamboo juice has the effect of enhancing the nasal cavity pain relieving effect of matched use of the baical skullcap root and the szechuan lovage rhizome; and grassleaf sweelflag rhizome, thunberg fritillary bulb and platycodon root are combined together to play roles of inducing resuscitation and refreshing, dispelling wind, clearing heat and resolving hard mass and detoxifying.

The adjuvant medicine adopts Poria and herba Agastaches for use, and has effects of eliminating dampness. Moisture removal is also indicated because of the sometimes accompanied moisture in the symptoms of wind-heat rhinitis.

The preparation method has the advantages that the peppermint is adopted as the guiding drug, so that the effects of harmonizing monarch drugs, ministerial drugs and adjuvant drugs are achieved; and the patient can feel cool nasal cavity, thereby playing a role of waking nose.

Compared with the prior art, the anti-rhinitis traditional Chinese medicine composition with the pain relieving effect has the beneficial effects that:

1. in the prior art, the bamboo juice is used for clearing heat and resolving phlegm, and has no pain relieving effect; however, the inventors of the present invention have unexpectedly found, through a number of exploratory experimental studies: when the bamboo juice and the baical skullcap root-szechuan lovage rhizome medicines are used together, the pain relieving effect of the single baical skullcap root-szechuan lovage rhizome medicines can be obviously enhanced, the synergistic effect is achieved, and the innovation is realized.

2. The traditional Chinese medicine composition provided by the invention has single and definite treatment purpose, and is capable of relieving pain of the nasal cavity caused by the wind-heat rhinitis and simultaneously has the treatment effect caused by the wind-heat rhinitis; not all kinds of rhinitis are suitable as described in the prior art, or can be used for treating rhinitis and simultaneously treating complications such as turbinate hypertrophy and the like.

3. Based on a single and definite therapeutic purpose, the prescription of the invention has scientific and reasonable compatibility design, accurate and controllable medication, uses baikal skullcap root, szechuan lovage rhizome and the like as monarch drugs and uses bamboo juice and the like as ministerial drugs, and has better analgesic effect compared with the known analgesic drugs (such as analgin injection and the like) on the market.

4. The Chinese medicinal composition provided by the invention adopts the bamboo juice as the ministerial drug, is not simply replaced, and is screened after comparing the medicinal materials of the bamboo juice, the bamboo shavings and the like with the baical skullcap root-szechuan lovage rhizome drug for use, and the user can really play a role in synergy. Both the succus Bambusae and caulis Bambusae in Taenia are derived from Gramineae plant bamboo, the succus Bambusae is juice extracted from processed bamboo, and caulis Bambusae in Taenia is obtained by processing dried middle layer of bamboo stalk; both have the effects of clearing heat and resolving phlegm, and neither have analgesic effects, but when combined with the baical skullcap root-szechuan lovage rhizome medicine, the inventor has found that: only the bamboo juice can play a role in synergy of the baical skullcap root-szechuan lovage rhizome medicines to achieve synergy and pain relieving, but the bamboo shavings cannot play a role in synergy and pain relieving.

In conclusion, the anti-rhinitis traditional Chinese medicine composition with the pain relieving effect is reasonable in compatibility design, scientific in monarch, minister, assistant and guide, single and clear in treatment purpose, and creatively uses bamboo juice as ministerial medicine and monarch medicine containing a baical skullcap root-szechuan lovage rhizome medicine pair, so that an unexpected treatment effect of synergistic and pain relieving of the synergistic monarch medicine is achieved; in addition, the prescription provided by the invention can also effectively treat allergic rhinitis, lighten the irritation of the medicine to rhinitis patients, and has great clinical application value and market development potential.

Drawings

Fig. 1 is a schematic diagram of a preparation process flow of the anti-rhinitis traditional Chinese medicine composition provided by the invention.

Fig. 2 is a comparison of the number of intranasal scratching (mean±sd, n=6) for each experimental group of rats in example 8; in contrast to the set of models, ^* p<0.05， ^** p<0.01; in comparison with the positive control group, ^△ p<0.05， ^△△ p<0.01。

FIG. 3 is a graph showing pain threshold comparison (mean) at various time points for rats of example 10SD, n=3); in contrast to the set of models, ^* p<0.05， ^** p<0.01; in comparison with the positive control group, ^△ p<0.05， ^△△ p<0.01。

Detailed Description

The following are specific examples of the present invention, and the technical solutions of the present invention are further described, but the scope of the present invention is not limited to these examples. All changes and equivalents that do not depart from the gist of the invention are intended to be within the scope of the invention.

Example 1 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

in the traditional Chinese medicine composition provided by the invention, the prescription and the dosage of the traditional Chinese medicine raw materials are specifically as follows, calculated by 1000 mL:

monarch drug: 240g of radix scutellariae, 240g of ligusticum wallichii, 200g of magnolia flower and 150g of radix angelicae;

ministerial drugs: 160g of succus bambusae, 270g of rhizoma acori graminei, 250g of fritillaria thunbergii and 290g of platycodon grandiflorum;

adjuvant drug: 250g of poria cocos and 260g of wrinkled gianthyssop;

the preparation method comprises the following steps: 190g of peppermint.

2. Preparation process (for example, see fig. 1 for preparation of nasal spray):

Example 2 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

monarch drug: 200g of radix scutellariae, 250g of ligusticum wallichii, 200g of magnolia flower and 150g of radix angelicae;

ministerial drugs: 150g of succus bambusae, 270g of rhizoma acori graminei, 250g of fritillaria thunbergii and 290g of platycodon grandiflorum;

adjuvant drug: 250g of poria cocos and 260g of wrinkled gianthyssop;

the preparation method comprises the following steps: 190g of peppermint.

2. The preparation process (taking the preparation of nasal spray as an example):

as in example 1.

Example 3 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

monarch drug: 250g of baical skullcap root, 290g of szechuan lovage rhizome, 200g of magnolia flower and 150g of dahurian angelica root;

ministerial drugs: 180g of succus Bambusae, 270g of rhizoma acori graminei, 250g of Bulbus Fritillariae Thunbergii, and 290g of radix platycodi;

adjuvant drug: 250g of poria cocos and 260g of wrinkled gianthyssop;

the preparation method comprises the following steps: 190g of peppermint.

as in example 1.

Example 4 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

Monarch drug: 250g of radix scutellariae, 200g of ligusticum wallichii, 200g of magnolia flower and 150g of radix angelicae;

adjuvant drug: 250g of poria cocos and 260g of wrinkled gianthyssop;

the preparation method comprises the following steps: 190g of peppermint.

as in example 1.

Example 5 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

monarch drug: 240g of radix scutellariae, 300g of ligusticum wallichii, 200g of magnolia flower and 150g of radix angelicae;

adjuvant drug: 250g of poria cocos and 260g of wrinkled gianthyssop;

the preparation method comprises the following steps: 190g of peppermint.

as in example 1.

Example 6 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

monarch drug: 200g of radix scutellariae, 200g of ligusticum wallichii, 150g of magnolia flower and 100g of radix angelicae;

ministerial drugs: 150g of succus Bambusae, 200g of rhizoma acori graminei, 200g of Bulbus Fritillariae Thunbergii, and 200g of radix platycodi;

adjuvant drug: 200g of poria cocos and 250g of wrinkled gianthyssop;

The preparation method comprises the following steps: 100g of peppermint.

as in example 1.

Example 7 the Chinese medicinal composition provided by the invention

1. Prescription and dosage:

monarch drug: 250g of baical skullcap root, 300g of szechuan lovage rhizome, 300g of magnolia flower and 200g of dahurian angelica root;

ministerial drugs: 180g of succus Bambusae, 300g of rhizoma acori graminei, 300g of Bulbus Fritillariae Thunbergii, and 400g of radix Platycodi;

adjuvant drug: 300g of poria cocos and 300g of wrinkled gianthyssop;

the preparation method comprises the following steps: 300g of peppermint.

as in example 1.

EXAMPLE 8 evaluation of anti-inflammatory Effect and nasal pain-relieving Effect of the Chinese medicinal composition provided by the invention on AR rats

1. The purpose of the experiment is as follows:

the experiment aims at researching the anti-inflammatory effect of the traditional Chinese medicine composition provided by the invention on Allergic Rhinitis (AR) mice and the preliminary evaluation on the nasal cavity pain relieving effect of the AR mice.

In this experiment, taking the prescription of example 1 of the present invention as an example, we define "(radix Scutellariae+rhizoma Chuanxiong): (succus Bambusae) =3:1 "is a high dose group, and only the ratio of" sum of Scutellariae radix and rhizoma Ligustici Chuanxiong "to succus Bambusae is changed, and the difference of antiinflammatory effect and nasal cavity analgesic effect at high, medium and low doses is examined without changing other Chinese medicinal materials and dosage.

2. Experimental animal

Kunming mice, male and female halves, have a weight of 18-22 g and are provided by the university of Zhejiang laboratory animal center.

Feeding conditions: constant temperature, 22+/-2 ℃ and 50% -60% humidity, and the ambient brightness and darkness of illumination for 14 hours and darkness for 10 hours are alternated, and the air exchanging times are 15-20 times per hour. Is fed by animal experiment center of Zhejiang university of Chinese medicine.

3. The experimental method comprises the following steps:

after 36 healthy mice were adaptively bred for one week, they were randomly divided into 6 groups of 6 mice each, namely: (1) normal group (no modeling, no administration), (2) model group (modeling only, no administration), (3) positive control group (modeling + administration of commercial olopatadine hydrochloride nasal spray), (4) high dose drug group (modeling + administration of the present invention provided traditional Chinese medicine composition), (5) medium dose drug group (modeling + administration of the present invention provided traditional Chinese medicine composition), (6) low dose drug group (modeling + administration of the present invention provided traditional Chinese medicine composition).

Wherein,

the high dose pharmaceutical composition is the prescription of example 1 of the present invention, wherein the dosage ratio of (baikal skullcap root + chuanxiong rhizome) to bamboo juice is =3:1;

the medium dose pharmaceutical composition is similar to the prescription of example 1, in which the dosage ratio of (radix Scutellariae+rhizoma Chuanxiong) to succus Bambusae is changed to be=2:1, and the other Chinese medicinal materials are the same as in example 1;

The low dose pharmaceutical composition was similar to the prescription of example 1, in which the ratio of (baikal skullcap root + chuanxiong rhizome) to bamboo juice was changed only=1:1, and the other Chinese medicines were similar and used in the same manner as in example 1.

Except for the normal group, the mice of the other 5 experimental groups were instilled with equal amounts of 10% Ovalbumin (OVA) in the nasal cavities on days 7 and 14, respectively, and challenged on day 28, resulting in a model of allergic rhinitis in the mice. And the following day after the challenge, the model mice all showed changes in the behavior of typical allergic rhinitis such as nasal red, scratching on the periphery of the nose (recording scratching times), frequent sneezing, etc., while the normal group did not show the above behavior. The positive control group, the high, medium and low dose drug groups were administered on the next day after challenge, respectively, for 10 days. Mice were treated 24h after the last dose and each index was examined. Comprising the following steps: 1) Serum is taken to measure immunological indexes; 2) HE staining, histopathological observations of mouse nasal mucosal tissue.

4. Experimental results and analysis

SPSS software is adopted to carry out statistical analysis on detection results, metering data is expressed in a form of (mean+ -SD), paired t test is adopted for comparison in groups, independent sample t test is adopted for comparison between groups, and P <0.05 is used for expressing difference, so that the statistical significance is achieved.

Nasal mucosa pathological histological changes after HE staining

From the observation of the HF staining results, it was found that: (1) normal group mice have normal nasal septum mucosal tissue structure; (2) the epithelial tissue cells of the nasal septum of the mice in the model group are obviously thickened, the cells are increased, the matrix is scalized, a large number of lymphocytes, mast cells and eosinophils are formed, the matrix of the nasal mucosa is swollen, and the tissues are loose; (3) the positive control group after administration and the high, medium and low dose drug groups have different degrees of alleviation of pathological changes such as thickening, scaling, inflammatory cell infiltration, interstitial swelling and the like of the nasal septum mucosa of the mice.

2. Serum immunological index variation

IgM and IgG antibody levels can be used for characterizing the therapeutic effect of the drug on the allergic rhinitis of AR mice, and the IgM and IgG antibody levels in the serum of the mice in each experimental group are measured, and the results are shown in Table 1.

Table 1. Influence of each experimental group on the immunological index of mice (mean.+ -. SD, n=6)

Group of	IgM value (g/L)	IgG value (g/L)
			Normal group	0.23±0.03 ^**	0.04±0.02 ^**
Model group	0.49±0.10	0.26±0.11
			Positive control group	0.34±0.12 ^*	0.12±0.10 ^*
Low dose pharmaceutical combination	0.48±0.11 ^△	0.28±0.13 ^△
			Medium dose pharmaceutical set	0.30±0.11 ^*	0.14±0.07 ^*
High dose pharmaceutical set	0.25±0.09 ^**	0.10±0.07 ^**

Compared with the model group, ^* p<0.05， ^** p<0.01; in comparison with the positive control group, ^△ p<0.05， ^△△ p<0.01。

as can be seen from table 1:

(1) compared with the normal group, the IgM and IgG values of the model group are obviously increased (p < 0.01), which indicates that the IgM and IgG antibody levels of mice after modeling are extremely obviously increased.

(2) Compared with the model group, the positive control group has significantly reduced IgM and IgG values (p < 0.05), which indicates that IgM and IgG antibody levels of model mice are significantly reduced after the positive control drug is administered; the positive control was a commercially available AR therapeutic agent, and thus it was found that the molding was successful.

(3) Compared with the model group, the IgM and IgG values of the high-dose drug group are obviously reduced (p is less than 0.01), and the IgM and IgG values of the medium-dose drug group are also obviously reduced (p is less than 0.05), which indicates that the high-dose and medium-dose drug group can obviously improve the IgM and IgG antibody levels of the model-making mice and has obvious anti-inflammatory effect; the IgM and IgG values of the low-dose medicine group are not obviously changed (p is more than 0.05), and the values approach to the model group, so that the low-dose medicine group has no obvious anti-inflammatory effect.

(4) Compared with the positive control group, the IgG value of the high-dose drug group is slightly better than that of the positive control group, and the IgM values of the high-dose drug group and the medium-dose drug group are slightly better than that of the positive control group, so that the anti-inflammatory effect is slightly better than that of the positive control group; the IgM and IgG values of the low-dose medicine group are obviously higher than those of the positive control group (p < 0.05), and further prove that the low-dose medicine group has no obvious anti-inflammatory effect.

3. Variation of the number of paranasal scratches in model mice

Since nasal pain accompanied by allergic rhinitis also causes behavioral changes in the model mice around the scratching nose (i.e., the painful parts), the difference in analgesic effect of each experimental group can also be judged by comparing and analyzing the behavioral changes of the model mice in each experimental group by recording the scratching times within two minutes after 0.5h of administration. The results are shown in Table 2 and FIG. 2.

Table 2. Influence of each experimental group on the nasal analgesic effect of mice (mean.+ -. SD, n=6)

Group of	Number of scratching times	Pain improvement rate (%)
			Normal group	5.5±1.9 ^**
Model group	42.0±9.3
			Positive control group	37.7±8.9	10.7
Low dose pharmaceutical combination	39.2±9.4	7.2
			Medium dose pharmaceutical set	27.3±6.9 ^*△	35.4
High dose pharmaceutical set	17.2±9.6 ^**△△	61.6

as can be seen from table 2 and fig. 2:

(1) compared with the normal group, the number of times of scratching the nose of the mice in the model group is obviously increased, and the significant difference (p < 0.01) exists, so that the successful modeling is judged.

(2) The mice in the positive control group had a somewhat reduced number of weeks of scratching, but did not have significant differences (p > 0.05), compared to the model group, indicating that the positive control drug was not found to have significant pain-improving effect temporarily at 0.5h of administration.

(3) The number of mouse noses Zhou Saozhua was extremely significantly reduced in the high dose drug group compared to the model group, with significant differences (p < 0.01); the number of mouse noses Zhou Saozhua in the medium dose drug group was significantly reduced with significant differences (p < 0.05); the number of mouse noses Zhou Saozhua in the low dose drug group was hardly reduced, and there was no significant difference (p > 0.05); the traditional Chinese medicine composition provided by the invention has the effect of relieving the pain of the nasal cavity in the high and medium dose groups when the administration is carried out for 0.5 h.

(4) The number of mouse noses Zhou Saozhua was extremely significantly reduced in the high dose drug group compared to the positive control group, with significant differences (p < 0.01); the number of mouse noses Zhou Saozhua in the medium dose drug group was significantly reduced with significant differences (p < 0.05); the number of mouse noses Zhou Saozhua in the low dose drug group was hardly reduced, and there was no significant difference (p > 0.05); the traditional Chinese medicine composition provided by the invention has better pain relieving effect in high and medium dosage groups.

Further, the pain improvement rates of the high, medium and low dose drug groups were calculated, the calculation results are shown in table 2, and the calculation formulas are as follows: pain improvement rate (%) = (number of scratches of model group-number of scratches of drug group)/(number of scratches of model group x 100%).

The results show that: the Chinese medicinal composition provided by the invention has the effects of relieving pain symptoms to different degrees in high-dose and medium-dose groups, and particularly has the best pain improvement effect in the high-dose medicinal group; the pain-improving effect of the low-dose drug group was not found at the time of administration for 0.5 h.

Considering the above 3 evaluation results of the test indexes, the optimal prescription of the high-dose drug group (i.e., example 1 of the present invention) is finally determined.

EXAMPLE 9 comparative analgesic Effect of drugs

1. The purpose of the experiment is as follows:

based on the embodiment 8, the experiment aims at analyzing and screening which proper ministerial drugs can play a role in coordinating the synergistic and analgesic effects of the monarch drugs. Therefore, the experiment is carried out by examining the differential influence of adding or not adding bamboo juice and adding or not adding bamboo shavings on the analgesic effect so as to screen out proper ministerial drug components.

2. Experimental animal

3. Experimental method

Measuring pain response of a mouse by adopting a hot plate method, taking healthy mice, adaptively raising the mice for one week, modeling the mice by adopting the method of the embodiment 8, placing the modeled AR mice on a constant-temperature hot plate instrument, generating pain response (namely licking hind feet) after the mice are heated and stimulated (55.0+/-0.5) DEG C, and calculating pain threshold(s) of the mice according to the time from the mice are thrown into the hot plate to the occurrence of the licking hind feet; all pain threshold values <5s, or >60s, or those who frequently jump on a hotplate apparatus are discarded.

42 mice with pain threshold meeting the requirement are taken, the weight of the mice is weighed, the mice are randomly divided into 7 groups, and 6 mice in each group are: (1) model group (no drug administration, physiological saline injection) and (2) positive control group (analgin injection administration), and (3) drug group A (drug administration succus Bambusae+radix Scutellariae+rhizoma Ligustici Chuanxiong), (4) drug group B (drug administration caulis Bambusae in Taenia+radix Scutellariae+rhizoma Ligustici Chuanxiong), (5) drug group C (drug administration radix Scutellariae+rhizoma Ligustici Chuanxiong), (6) comparative example group 1 (drug administration succus Bambusae) and (7) comparative example group 2 (drug administration caulis Bambusae in Taenia).

Wherein,

the medicine group A is a prescription of the embodiment 1 of the invention, wherein the principal medicine contains baical skullcap root and szechuan lovage rhizome, the ministerial medicine contains bamboo juice, and the prescription is counted as a group of 'bamboo juice + baical skullcap root + szechuan lovage rhizome';

the medicine group B is a prescription similar to the example 1, wherein the principal medicine contains baical skullcap root and szechuan lovage rhizome, the ministerial medicine contains bamboo shavings but does not contain bamboo juice (replacement), and the prescription is counted as a group of 'bamboo shavings + baical skullcap root + szechuan lovage rhizome';

the medicine group C is a prescription similar to the embodiment 1, wherein the principal medicine contains baical skullcap root and szechuan lovage rhizome, the ministerial medicine contains neither bamboo juice nor bamboo shavings (taste reduction), and the other traditional Chinese medicines are the same as the embodiment 1 in types and dosage, and are counted as a 'baical skullcap root and szechuan lovage rhizome' group;

the water-decoction-alcohol-precipitation solution is prepared by the method of the drug group A, the drug group B and the drug group C according to the literature (Chen Min, xia Shouming. The study of the anti-inflammatory and analgesic effects of baikal skullcap root on mice [ J ]. Anhui agricultural report. 2020,26 (15): 34-35.), and the main drugs in the drug group B and the drug group C are supplemented with the solvent for the balance so as to ensure the influence contrast of the single factor level, so that the water-decoction-alcohol-precipitation solution containing the main drug components with the concentration of the drug group A and the like is prepared.

In addition, the inventors have prepared a simple succus Bambusae ethanol precipitation solution and a simple succus Bambusae Ru Chun precipitation solution in the same way to examine whether succus Bambusae or caulis Bambusae in Taenia has analgesic effect by itself, see comparative example 1 and comparative example 2 (the balance of main drug is supplemented with solvent, and the concentrations of the main drug components of drug group A are equal).

The positive control group is administrated with commercial analgin injection, and the dosage of main medicine components in the injection is equal to that of main medicine components in medicine group A, medicine group B and medicine group C.

Mice meeting the requirement of the pain threshold are subjected to intraperitoneal injection or gastric lavage administration, and the mice are continuously administered for 6 days, 1 time a day. The normal pain threshold of each mouse was measured before administration, and the average value of 2 times was taken as the pain threshold of the mice before administration, and the change of the pain threshold was measured after administration for 30 min. The calculation formula of pain threshold increment and pain threshold improvement rate is as follows:

pain threshold proliferation(s) =post-dose pain threshold(s) -pre-dose pain threshold(s);

pain threshold increase rate (%) = pain threshold increment (s)/(pain threshold before administration(s) ×100%).

4. Experimental results and analysis

SPSS software is adopted to carry out statistical analysis on detection results, metering data is expressed in a form of (mean+ -SD), paired t test is adopted for comparison in groups, independent sample t test is adopted for comparison between groups, and P <0.05 is used for expressing difference, so that the statistical significance is achieved. The results are shown in Table 3.

Table 3 comparison of analgesic effects of different experimental groups (mean±sd, n=6)

Compared with the pain threshold before administration, ^* p<0.05， ^** p<0.01; in comparison with the set of models, ^△ p<0.05， ^△△ p<0.01; in comparison with the group C of drugs, ^# p<0.05， ^## p<0.01; in comparison with the positive control group, ^★ p<0.05， ^★★ p<0.01。

as can be seen from table 3:

(1) the pain threshold value after the administration of the positive control group, the drug group A, the drug group B and the drug group C is obviously increased (p < 0.01) compared with the pain threshold value before the administration, and the pain increment after the administration of the model group, the comparative example group 1 and the comparative example group 2 is not obviously increased (p > 0.05);

compared with the model group, the pain threshold increment and the pain threshold increment rate of the drug group A, the drug group B and the drug group C are obviously improved (p < 0.01), and the pain threshold increment rate of the comparative example group 1 and the comparative example group 2 are not obviously improved (p > 0.05);

this indicates that: the positive control group, the drug group A, the drug group B and the drug group C all have pain relieving effects with different degrees; the comparative example 1 and the comparative example 2 did not have an analgesic effect, i.e., the single succus Bambusae or caulis Bambusae in Taenia did not have an analgesic effect.

(2) Compared with the model group, the pain threshold increment and the pain threshold increment rate of the positive control group are all obviously improved (p < 0.01), so that the modeling is successful.

(3) Compared with the medicine group C, the pain threshold increment and the pain threshold improvement rate of the medicine group A are both obviously improved (p is less than 0.01), which indicates that the pain relieving effect is obviously stronger than that of a formula containing no bamboo juice or bamboo shavings and containing a baical skullcap root-szechuan lovage rhizome medicine pair when the ministerial medicine bamboo juice is combined with the monarch medicine, namely, the bamboo juice can play a role in synergism of the monarch medicine as the ministerial medicine;

The pain threshold increment and pain threshold improvement rate of the medicine group B are not obviously improved (p is more than 0.05), which indicates that when the ministerial medicine caulis bambusae in taeniam is combined with the same monarch medicine, the pain relieving effect is equivalent to that of a formula of the ministerial medicine containing no succus bambusae or caulis bambusae in taeniam and the monarch medicine containing the radix scutellariae-ligusticum chuanxiong medicine pair, namely the caulis bambusae in taeniam can not play a role in synergy of the monarch medicine as the ministerial medicine.

(4) Compared with the positive control group, the pain threshold increment and the pain threshold increment rate of the drug group A are obviously improved (p < 0.01), and the pain threshold increment rate of the drug group B and the drug group C are not obviously improved (p > 0.05); and from the data, the pain threshold increment and pain threshold improvement rate of the drug group B and the drug group C are close to those of the positive control group; the medicine has the advantages that the medicine group C and the medicine group C exert the analgesic effect by using the monarch medicine, and the medicine group A exerts the stronger analgesic effect by using the ministerial medicine, the bamboo juice and the monarch medicine, so the analgesic effect of the medicine group A is better than that of the analgin injection sold in the market.

EXAMPLE 10 analgesic efficacy time comparison experiment of drugs

1. Purpose of experiment

On the basis of example 9, the experiment further evaluates the difference in onset time of analgesic effect in drug group a (i.e., the prescription of example 1), positive control group (to which the commercial olopatadine hydrochloride nasal spray was administered), and model group (not to which the drug was administered).

2. Experimental animal

3. Experimental method

After healthy mice were adaptively bred for one week, the mice were sensitized and molded according to the method of example 8, the molded AR mice were placed on a constant temperature hotplate instrument, the pain threshold of each experimental group AR mice was measured according to the method of example 9, and mice with the pain threshold meeting the requirements were selected.

9 mice with pain threshold meeting the requirement are taken, the weight of the mice is weighed, the mice are randomly divided into 3 groups, and 3 mice in each group are: model group (no drug administration), positive control group (drug administration of commercial olopatadine hydrochloride nasal spray), drug group A (drug administration of the prescription of example 1), pain threshold values of AR mice of each experimental group were measured at 5 time points of pre-drug administration (0 h), post-drug administration (0.5 h, 1h, 2h, 4 h) according to the method of example 9, and the test results were curve-fitted (see FIG. 3), and the difference in analgesic onset time of each experimental group was analyzed and compared.

4. Experimental results and analysis

SPSS software is adopted to carry out statistical analysis on detection results, metering data is expressed in a form of (mean+ -SD), paired t test is adopted for comparison in groups, independent sample t test is adopted for comparison between groups, and P <0.05 is used for expressing difference, so that the statistical significance is achieved. The results are shown in Table 4.

Table 4 pain threshold comparison (mean+ -SD, n=3) at various time points for each experimental group

	0h	0.5h	1h	2h	4h
						Model group	12.26±1.19	12.27±1.19	12.28±1.18	12.27±1.62	12.26±1.34
Positive control group	12.58±0.79	13.70±0.78	21.91±1.77 ^**	17.39±0.73 ^**	17.25±0.72 ^**
						Pharmaceutical group A	12.82±0.42	24.28±0.63 ^**△△	23.23±0.76 ^**	19.55±1.83 ^**	19.35±1.96 ^**

as can be seen from fig. 3 and table 4:

(1) compared with the model group, the positive control group has significantly increased pain threshold (p < 0.01) when self-administration is carried out for 1h, and has almost no change (p > 0.05) when administration is carried out for 0.5 h; drug group a had a significant increase in onset pain threshold (p < 0.01) from 0.5h self-administration.

(2) Compared with the positive control group, the pain threshold of the drug group A is significantly higher than that of the positive control group (p < 0.01) when the drug group A is dosed for 0.5 h; at 1h, 2h, and 4h, the pain threshold of drug group a was higher than that of the positive control group but there was no significant difference (p > 0.05).

(3) From the point of view of the trend of the numerical value variation,

before administration (i.e. 0 h), the initial pain threshold values of the model group, the positive control group and the drug group A are similar (p > 0.05);

the pain threshold of the positive control group starts to rise significantly from 0.5h to 1h after administration, and the pain threshold rises to a peak value (21.91 +/-1.77) at 1h after administration, which is significantly higher than that of the model group (p < 0.01); 1 h-2 h after dosing significantly decreased, 2 h-4 h after dosing tended to be stationary but still higher than model group (p < 0.01);

The pain threshold of the drug group A starts to rise obviously after 0 h-0.5 h, and the pain threshold rises to a peak value (24.28+/-0.63) at 0.5h after the drug group A is obviously higher than that of a model group and a positive control group (p is equal to 0.01); slowly declined from 0.5h to 2h after dosing, and tended to be smooth but still higher than the model group (p < 0.01) for 2h to 4h after dosing.

To sum up, it is assumed that: the positive control group has the analgesic effect time within 0.5-1 h, and the drug group A has the analgesic effect time within 0-0.5 h, which indicates that the analgesic effect time of the drug group A is necessarily earlier than that of the positive control group, and the anti-inflammatory effect of the drug group A does not reach the peak value when the analgesic effect is achieved.

Example 12 safety test of the Chinese medicinal composition provided by the invention

1. Purpose of experiment

The experiment aims at comparing and analyzing the drug irritation of the traditional Chinese medicine composition (the prescriptions of examples 1-7) provided by the invention and a plurality of sprays such as a commercially available hydroxymethylouline hydrochloride spray and a mometasone furoate nasal spray to evaluate the safety of the drug.

2. Experimental animal

SD rats, male and female, have a weight of 150-200 g, and are qualified for quarantine and have no abnormal nasal appearance, and are provided by the Zhejiang university laboratory animal center.

3. Experimental materials

Medicament: 0.9% sodium chloride injection, spray prepared according to the prescriptions of the examples 1-7 of the invention, hydroxymaline hydrochloride spray, mometasone furoate nasal spray;

And (3) equipment: ultrasonic atomizer, protector, rat dissecting and killing equipment, etc.

4. Experimental method

100 rats were randomly allocated to a control group (0.9% sodium chloride injection), an experimental group prepared according to the prescriptions of examples 1-7, a commercial hydroxymethylou-linn hydrochloride spray experimental group, a commercial mometasone furoate nasal spray experimental group, 10 rats per group, 10 total groups, and each half of male and female; spraying and administering to the male and female rats of each experimental group, wherein the administration concentration is the stock solution (10 g/L), the administration volume is about 4ml, and the male and female rats of the control group are administered with an equal volume of 0.9% sodium chloride injection;

the ultrasonic atomizer is used for fixing the rat in the retainer, and the spraying pipe is opposite to the nose of the rat, so that the rat can fully inhale the medicine. The nebulization time of each rat was 20min, 3 times per 1 week, and 4 weeks total. Before and 30min after each administration, 24, 48, 72h and 14d after the last administration, observing whether there are red swelling, bleeding, ulcer and other phenomena in the visible range inside and outside the mouth and nose of the animal, especially noticing the local reaction of the change condition of the mucous membrane of the nose, and expressing the local mucous membrane by scoring according to the local mucous membrane stimulating reaction grading standard, including edema, congestion degree, range and the like, and observing the general condition (such as respiration, circulation, central nervous system and the like) and local stimulating symptoms (such as asthma, cough, vomiting, asphyxia and the like) of the animal 30min after the administration;

Animals were dissected in batches, lung weights were weighed and the viscera coefficients were calculated, then the nose, throat, trachea, bronchi and lungs of the animals were extracted for fixation, and histopathological examination was performed after observation of the presence or absence of congestion, edema, ulcers, and the like.

And (3) observing the indexes:

A. animal appearance characteristics, behavioural activities, respiration and faecal traits

B. Whether there is red swelling, bleeding, ulcer and the like in the visible range outside the mouth and nose

C. Conditions in the visible range of the nasal mucosa

D. General conditions (e.g. respiratory, circulatory, central nervous system, etc.) and local irritation symptoms (e.g. asthma, cough, vomiting, asphyxia, etc.)

E. Whether the tissue and cell arrangement of various levels of bronchi in nose, throat, tracheal mucosa layer and lung are tightly ordered, the morphology is regular, the structure is normal, cilia are clearly visible, whether the submucosa is subjected to vasodilation and inflammatory reaction, and whether the surrounding bone tissue and cartilage tissue structure are changed

F. Whether the lung weight is changed or not

5. Experimental results and analysis

The qualitative index observations of the blank group and each experimental group are specified as follows according to the rule of "4) observation index" of "fourth experimental method":

1) Control group: sodium chloride injection with concentration of 0.9%

The animal has normal appearance characteristics, behavioural activities, respiration and fecal properties, has no red swelling, bleeding, ulcer and other phenomena in the visible range outside the mouth and nose, has compact and orderly tissue and cell arrangement of various levels of bronchi in the nose, throat, tracheal mucosa layer and lung, has regular morphology and normal structure, has clear cilia, has no vasodilation and inflammatory reaction under the mucosa, has no change in surrounding bone tissue and cartilage tissue structure, and has no change in lung weight. The male and female mice are basically indistinguishable.

2) Experimental group of the invention: spray formulations prepared according to the inventive examples 1-7

The animal has normal appearance characteristics, behavioural activities, respiration and fecal properties, has no red swelling, bleeding, ulcer and other phenomena in the visible range outside the mouth and nose, has compact and ordered arrangement of tissues and cells of various levels of bronchi in the nose, throat, tracheal mucosa and lung, has regular morphology and normal structure, has clear cilia, has slight vasodilation and inflammatory reaction under the mucosa, has no change in the surrounding bone tissue and cartilage tissue structure, and has no change in the weight of the lung. The male and female mice are basically indistinguishable.

3) Experimental group of commercial drugs: hydroxymaline hydrochloride spray

Animal appearance characteristics, behavioural activities and fecal properties are normal, the breath is rapid, the visible range outside the mouth and the nose has the phenomena of redness, bleeding, ulcer and the like, tissues and cells of various levels of bronchi in the nose, throat, tracheal mucosa layers and lungs are loosely arranged, the morphology is regular, the structure is normal, cilia are clearly visible, moderate vasodilation and inflammatory reaction are seen under the mucosa, the structures of surrounding bone tissues and cartilage tissues are not changed, and the weight of the lung is slightly heavier. The male and female mice are basically indistinguishable.

4) Experimental group of commercial drugs: mometasone furoate nasal spray

The animal has normal appearance characteristics, behavioural activities, respiration and fecal properties, has slight red swelling, bleeding, ulcer and other phenomena in the visible range outside the mouth and nose, has compact and orderly tissue and cell arrangement of various levels of bronchi in the nose, throat, tracheal mucosa and lung, has regular morphology and normal structure, is clear and visible in cilia, has no change in the structures of peripheral bone tissues and cartilage tissues and has no change in the weight of the lung, and the animal has no change in the structures of peripheral bone tissues and cartilage tissues. The male and female mice are basically indistinguishable.

From the qualitative observation results of the foregoing experiments, the stimulatory effects of the drugs in each experimental group on the nasal mucosa are sequentially ordered from small to large as follows: nasal spray prepared according to the prescriptions of examples 1 to 7 of the present invention > mometasone furoate nasal spray > hydroxymaline hydrochloride spray.

Therefore, the nasal spray of the traditional Chinese medicine composition prepared by the invention has good safety and better effect than the commercial nasal spray of western medicines.

Claims

1. The anti-rhinitis traditional Chinese medicine composition is characterized by being prepared from the following traditional Chinese medicine raw materials in parts by weight: the traditional Chinese medicine comprises the following components in parts by mass: 20-25 parts of radix scutellariae, 20-30 parts of ligusticum wallichii, 15-30 parts of magnolia flower, 10-20 parts of radix angelicae, 15-18 parts of bamboo juice, 20-30 parts of rhizoma acori graminei, 20-30 parts of fritillaria thunbergii, 20-40 parts of radix platycodi, 20-30 parts of poria cocos, 25-30 parts of wrinkled gianthyssop and 10-30 parts of mint; wherein the sum of the dosage of the baical skullcap root and the Szechuan lovage rhizome is 2-4 times of the dosage of the bamboo juice.

2. The anti-rhinitis traditional Chinese medicine composition according to claim 1, wherein the sum of the dosage of the baikal skullcap root and the Ligusticum wallichii is 3 times of the dosage of the bamboo juice in the traditional Chinese medicine raw materials.

3. The anti-rhinitis traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by mass: 24 parts of baical skullcap root, 24 parts of szechuan lovage rhizome, 20 parts of magnolia flower, 15 parts of dahurian angelica root, 16 parts of bamboo juice, 27 parts of grassleaf sweelflag rhizome, 25 parts of thunberg fritillary bulb, 29 parts of platycodon root, 25 parts of Indian buead, 26 parts of wrinkled gianthyssop herb and 19 parts of mint.

4. The anti-rhinitis traditional Chinese medicine composition according to any one of claims 1 to 3, further comprising an auxiliary material.

5. The anti-rhinitis traditional Chinese medicine composition according to claim 4, wherein the auxiliary material comprises a preservative.

6. The anti-rhinitis traditional Chinese medicine composition according to any one of claims 1 to 3, wherein the dosage form of the traditional Chinese medicine composition is a nasal delivery system.

7. The anti-rhinitis traditional Chinese medicine composition according to claim 6, wherein the traditional Chinese medicine composition is in a form of a nasal liquid preparation, a nasal semisolid preparation or a nasal solid preparation.

8. The anti-rhinitis traditional Chinese medicine composition according to claim 7, wherein when the traditional Chinese medicine composition is a nasal liquid preparation, the traditional Chinese medicine composition is one dosage form selected from nasal drops, nasal washes and nasal sprays.

9. The anti-rhinitis traditional Chinese medicine composition according to claim 7, wherein when the traditional Chinese medicine composition is a semi-solid preparation for nose, the traditional Chinese medicine composition is one dosage form selected from nasal ointment, nasal cream and nasal gel.

10. The anti-rhinitis traditional Chinese medicine composition according to claim 7, wherein when the traditional Chinese medicine composition is a nasal solid preparation, the traditional Chinese medicine composition is one dosage form selected from nasal powder, nasal powder mist and nasal stick.

11. Use of an anti-rhinitis traditional Chinese medicine composition according to any one of claims 1 to 10 in the preparation of a medicament for treating wind-heat rhinitis.

12. The use according to claim 11, wherein the medicament for treating wind-heat rhinitis is used for treating nasal pain associated with wind-heat rhinitis.

13. The use according to claim 12, wherein the Chinese medicinal composition is in the form of a nasal spray, and is prepared from the following components in parts by weight: 24 parts of baical skullcap root, 24 parts of szechuan lovage rhizome, 20 parts of magnolia flower, 15 parts of dahurian angelica root, 16 parts of bamboo juice, 27 parts of grassleaf sweelflag rhizome, 25 parts of thunberg fritillary bulb, 29 parts of platycodon root, 25 parts of Indian buead, 26 parts of wrinkled gianthyssop herb and 19 parts of mint.

14. The use according to claim 12, wherein the Chinese medicinal composition is in the form of nasal spray, and each 1000mL of the preparation comprises the following components in parts by weight: 240g of baical skullcap root, 240g of szechuan lovage rhizome, 200g of magnolia flower, 150g of dahurian angelica root, 160g of bamboo juice, 270g of grassleaf sweelflag rhizome, 250g of thunberg fritillary bulb, 290g of platycodon root, 250g of Indian buead, 260g of wrinkled gianthyssop herb and 190g of peppermint, and 0.2-0.5 g of preservative; and is prepared through the following steps:

3) Recovering ethanol from the supernatant (1) and the supernatant (2) obtained in the step 2), refining the liquid medicine, adding auxiliary materials with the prescription amount after refining, and adjusting the volume of the liquid medicine to 1000ml to obtain a semi-finished product;

4) And (5) after the semi-finished product is inspected to be qualified, sterilizing and filling to obtain the finished product.