Nasal swelling reducer

Abstract

To provide novel pharmaceuticals that can improve swelling of the nasal cavity.SOLUTION: Shoseiryuto extract is an active ingredient of an agent for improving swelling of the nasal cavity. The agent for improving swelling of the nasal cavity that contains Shoseiryuto extract is particularly preferably applied to non-allergic and non-infectious symptoms without rhinorrhea.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent for improving nasal congestion.

Background Art

[0002] Rhinitis, that is, inflammation of the nasal mucosa, is characterized by rhinorrhea and nasal congestion, and one or both of these appear as symptoms. Causes of rhinitis include viral infection, bacterial infection, allergens, and non-allergic factors.

[0003] According to the 2013 Edition of the Nasal Allergy Treatment Guidelines (Non-Patent Document 1, hereinafter also referred to as the "Treatment Guidelines"), rhinitis is broadly classified into infectious, allergic non-infectious, irritant, and others. Infectious rhinitis is further classified into acute rhinitis (including colds) and chronic rhinitis (including chronic sinusitis). Allergic non-infectious rhinitis is further classified into complex type (so-called nasal allergy, including allergic rhinitis and non-allergic rhinitis), rhinorrhea type (including gustatory rhinitis, cold-air inhalation rhinitis, senile rhinitis), congestive type (including drug-induced rhinitis, psychogenic rhinitis, pregnancy rhinitis, endocrine rhinitis, cold-induced rhinitis), and dry type (including dry rhinitis). Irritant rhinitis is further classified into physical rhinitis, chemical rhinitis, and radiation rhinitis. Other rhinitis is classified into atrophic rhinitis and specific granulomatous rhinitis.

[0004] Thus, since the types of rhinitis vary widely depending on the cause, symptoms, etc., it has become clinical technical common sense that the treatment method is also selected according to the cause, symptoms, etc.

[0005] For example, with regard to allergic rhinitis, the clinical guidelines classify allergic rhinitis into three types based on the relative severity of sneezing / rhinorrhea symptoms and nasal congestion symptoms: "sneezing / rhinorrhea type" (where sneezing / rhinorrhea symptoms are more severe than nasal congestion symptoms), "nasal congestion type" (where nasal congestion is more severe than sneezing / rhinorrhea), and "complete type" (where sneezing / rhinorrhea and nasal congestion are of similar severity). The guidelines indicate that medication should be selected according to the severity of symptoms in each type. Specifically, the clinical guidelines recommend the following for "sneezing and runny nose type": second-generation antihistamines, release inhibitors, and nasal steroid sprays; for "full type primarily characterized by nasal congestion": anti-leukotriene (anti-LTs) drugs, anti-prostaglandin D2 (anti-PGD2) / thromboxane A2 drugs (TXA2 drugs), Th2 cytokine inhibitors, and nasal steroid sprays; and for "full type primarily characterized by nasal congestion": the combination of nasal steroid sprays with anti-LTs drugs or anti-PGD2 / TXA2 drugs.

[0006] Thus, the clinical guidelines indicate that nasal congestion should be treated with nasal spray steroids, etc., and antihistamines are not indicated. This is an established clinical theory, as evidenced by the clinical guidelines stating that "antihistamines are generally effective for sneezing and runny nose, but their effect on nasal congestion is not strong, so short-acting nasal vasoconstrictors are used for patients with severe nasal congestion and mucosal swelling," and Non-Patent Document 2 stating that "for nasal congestion, antihistamine and anticholinergic components do not provide sufficient relief, so we recommend nasal sprays containing vasoconstrictors that stimulate α1 receptors in capillaries and constrict congested nasal mucosal blood vessels."

[0007] Incidentally, in recent years, the demand for herbal medicine prescriptions has been steadily increasing, and opportunities to use herbal medicines are growing, both for self-medication and through prescriptions from physicians. For this reason, guidelines have been established regarding the appropriate use of pharmaceuticals in herbal medicine treatment (Non-Patent Literature 3, also referred to as "Herbal Medicine Guidelines" hereafter).

[0008] The Kampo guidelines explain the selection of Kampo medicines for the acute phase of the common cold, including Kakkonto, Maoto, Daiseiryuto, Shoseiryuto, Maobushisaishinto, Keishieruppiitou, Keishimaohakuhanto, Keishito, Shinbuto, and Maobushisaishinto. Shoseiryuto is indicated as being applicable to symptoms such as "severe sneezing and runny nose." Furthermore, Shoseiryuto is the only Kampo medicine listed in the above clinical guidelines that has demonstrated effectiveness against "allergic rhinitis" in a placebo-controlled trial, and there are numerous clinical reports supporting its effectiveness.

[0009] From a Western medical perspective, the reported mechanisms of action of Xiao Qing Long Tang include histamine release inhibition (Non-Patent Documents 4 and 5), anti-allergic (PCA reaction inhibition) effects (Non-Patent Document 4), and antihistamine effects (Non-Patent Document 6). [Prior art documents] [Non-patent literature]

[0010] [Non-Patent Document 1] Nasal Allergy Treatment Guidelines 2013 Edition (7th Revised Edition), Nasal Allergy Treatment Guidelines Drafting Committee, Life Science, 2013. [Non-Patent Document 2] An Introduction to OTC Medications: Learning and Practicing How to Choose and Use Them [Revised 5th Edition], 2018 [Non-Patent Document 3] Guidelines for the Appropriate Use of Pharmaceuticals in Kampo Medicine Treatment, Japanese Respiratory Society, 2005. [Non-Patent Document 4] Outlook on Otorhinolaryngology, 34(Supplement 4) 289-293, 1991 [Non-Patent Document 5] Progress in Medicine 18:7;1659-1665, 1998 [Non-Patent Document 6] Otorhinolaryngology Clinical Practice 88:3;389-405, 1995 [Overview of the project] [Problems that the invention aims to solve]

[0011] As indicated in the diagnostic guidelines, antihistamines are used for rhinorrhea. Furthermore, as mentioned above, Xiao Qing Long Tang is a herbal medicine used for symptoms accompanied by nasal discharge, and its application as indicated in the diagnostic guidelines is reasonable considering its mechanism of action from a Western medical perspective, such as antihistamines and anti-allergics. In other words, since Xiao Qing Long Tang is used for rhinitis as an antihistamine or anti-allergic drug, it has not been used for symptoms of swelling and edema of the nasal mucosa, for which vasoconstrictors are indicated.

[0012] The present invention aims to provide a novel pharmaceutical product that can improve nasal cavity swelling. [Means for solving the problem]

[0013] The inventors, after diligent research, unexpectedly discovered that Xiao Qing Long Tang, which is supposed to be an antihistamine or anti-allergic drug, has the effect of improving nasal cavity swelling. This invention was completed by further research based on this finding.

[0014] In other words, the present invention provides inventions in the following embodiments. Item 1. A nasal swelling relief agent containing Xiao Qing Long Tang extract. Item 2. A nasal swelling reliever as described in Item 1, applicable to symptoms without rhinorrhea. Item 3. A nasal edema-reducing agent as described in Item 1 or 2, applicable to non-allergic symptoms. Item 4. A nasal edema reliever described in any of items 1-3, applicable to non-infectious symptoms. [Effects of the Invention]

[0015] The present invention provides a novel pharmaceutical product that can improve nasal cavity swelling. [Brief explanation of the drawing]

[0016] [Figure 1] This demonstrates the effect of a nasal cavity swelling-reducing agent on expanding the nasal passage area.

Best Mode for Carrying Out the Invention

[0017] The nasal congestion improver of the present invention is characterized by containing the extract of Xiaoqinglong Decoction. Hereinafter, the nasal congestion improver of the present invention will be described in detail.

[0018] Active ingredients The nasal congestion improver of the present invention contains the extract of Xiaoqinglong Decoction as an active ingredient. Xiaoqinglong Decoction is a mixed crude drug consisting of eight herbs: Ephedrae Herba, Armeniacae Semen Amarum, Paeoniae Radix Alba, Cinnamomi Ramulus (Zingiberis Rhizoma Recens is also acceptable), Glycyrrhizae Radix, Cinnamomi Cortex, Asari Herba, and Schisandrae Fructus, based on "Treatise on Febrile Diseases" and "Synopsis of the Golden Chamber".

[0019] In the present invention, the mixing ratio of the crude drugs constituting Xiaoqinglong Decoction is not particularly limited, but examples include 3 to 6 parts by weight of Ephedrae Herba, 2 to 3 parts by weight of Armeniacae Semen Amarum, 2 to 3 parts by weight of Paeoniae Radix Alba, 2 to 3 parts by weight of Cinnamomi Ramulus (Zingiberis Rhizoma Recens is also acceptable), 2 to 3 parts by weight of Glycyrrhizae Radix, 2 to 3 parts by weight of Cinnamomi Cortex, 2 to 3 parts by weight of Asari Herba, and 1.5 to 3 parts by weight of Schisandrae Fructus.

[0020] A preferred example of the crude drug preparation used for producing the extract of Xiaoqinglong Decoction in the present invention is a mixture of 6.0 parts by weight of Ephedrae Herba, 3.0 parts by weight of Armeniacae Semen Amarum, 3.0 parts by weight of Paeoniae Radix Alba, 3.0 parts by weight of Cinnamomi Ramulus, 3.0 parts by weight of Glycyrrhizae Radix, 3.0 parts by weight of Cinnamomi Cortex, 3.0 parts by weight of Asari Herba, and 3.0 parts by weight of Schisandrae Fructus.

[0021] The form of the extract of Xiaoqinglong Decoction may be any of liquid extracts such as liquid extracts and soft extracts, or solid dried extract powders.

[0022] The liquid extract of Xiao Qing Long Tang can be obtained by extracting a mixture of crude drugs according to the formula for Xiao Qing Long Tang and concentrating the resulting extract as needed. The extraction solvent used in the extraction process is not particularly limited, but water or aqueous ethanol is preferred. Furthermore, the dried extract powder of Xiao Qing Long Tang can be obtained by drying the liquid extract. The drying method is not particularly limited, but examples include spray drying or adding a suitable adsorbent (e.g., anhydrous silicic acid, starch, etc.) to a concentrated soft extract to obtain an adsorbent powder.

[0023] In the present invention, the Xiao Qing Long Tang extract may be the extract prepared by the method described above, or a commercially available extract may be used. For example, as a soft extract of Xiao Qing Long Tang, "Xiao Qing Long Tang Extract" (manufactured by Nippon Powder Pharmaceutical Co., Ltd.) and as a dry extract of Xiao Qing Long Tang, "Xiao Qing Long Tang Dry Extract-A", "Xiao Qing Long Tang Extract (27D·ATS)" (both manufactured by Nippon Powder Pharmaceutical Co., Ltd.), and "Xiao Qing Long Tang Dry Extract-F" (Alps Pharmaceutical Industry Co., Ltd.) are known products and can be obtained commercially.

[0024] In the nasal swelling improving agent of the present invention, the content of Xiao Qing Long Tang extract is not particularly limited as long as it achieves the effects of the present invention, but is usually 10 to 100% by weight, preferably 20 to 90% by weight, more preferably 40 to 80% by weight, and even more preferably 60 to 70% by weight, based on the amount of dried extract powder of Xiao Qing Long Tang extract. In the present invention, the amount of dried extract powder of Xiao Qing Long Tang refers to the amount of the dried extract powder itself when used, and the amount converted to the remaining amount after removing the solvent when using the liquid extract of Xiao Qing Long Tang. Furthermore, if the dried extract powder of Xiao Qing Long Tang contains additives such as adsorbents added during manufacturing, it refers to the amount excluding such additives.

[0025] Other ingredients The nasal swelling-improving agent of the present invention may consist solely of Xiao Qing Long Tang extract, or it may contain additives and bases depending on the formulation. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but examples include excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, etc. These additives may be used individually or in combination of two or more. Furthermore, the content of these additives and bases is appropriately set depending on the type of additive and base used, the formulation of the nasal swelling-improving agent, etc.

[0026] Furthermore, the nasal swelling-reducing agent of the present invention may contain other nutritional components and pharmacological components as needed, in addition to the Sho-seiryu-to extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but examples include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives and hypnotics, antihistamines, caffeines, cardiotonic and diuretic agents, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, menthols, etc. These nutritional components and pharmacological components may be used individually or in combination of two or more. The content of these components may be appropriately set depending on the type of component used.

[0027] Formulation The formulation form of the nasal swelling-improving agent of the present invention is not particularly limited as long as it can be administered orally, but examples include solid formulations such as powders, fine granules, granules, tablets, lozenges, chewable tablets, capsules (soft capsules, hard capsules), and pills; semi-solid formulations such as jellies; and liquid formulations such as liquids, suspensions, and syrups. Solid formulations are preferred, and tablets are more preferred.

[0028] Manufacturing method The method for producing the nasal swelling-reducing agent of the present invention is to use the above-mentioned herbal ingredients and formulate them according to the usual formulation methods used in the pharmaceutical field.

[0029] Purpose The nasal swelling-relieving agent of the present invention is used for the purpose of improving nasal swelling. Nasal swelling usually refers to a symptom that causes nasal congestion due to swelling of the nasal mucosa.

[0030] The nasal swelling-improving agent of the present invention is applicable to any symptom involving at least nasal swelling, regardless of whether or not there is nasal discharge, but it is particularly preferable that the symptom be one without nasal discharge.

[0031] The nasal swelling-reducing agent of the present invention is applicable to any nasal swelling, whether allergic or non-allergic, but is particularly preferred for non-allergic symptoms.

[0032] The nasal swelling-reducing agent of the present invention is applicable to any symptom involving nasal swelling, whether infectious or non-infectious, but is particularly preferred for non-infectious symptoms.

[0033] Particularly preferred examples of symptoms to which the nasal swelling-improving agent of the present invention is applied are symptoms accompanied by at least two of the following: symptoms without rhinorrhea, non-allergic symptoms, and non-infectious symptoms, with the most preferred example being symptoms without rhinorrhea, that are non-allergic and non-infectious.

[0034] Preferred specific examples of symptoms to which the nasal swelling-improving agent of the present invention is applicable include non-allergic rhinitis such as vasomotor rhinitis, eosinophilic rhinitis, and congestive rhinitis. Examples of congestive rhinitis include drug-induced rhinitis, psychogenic rhinitis (which develops due to chronic stress, depression, neurosis, etc.), pregnancy rhinitis (which develops from the second trimester of pregnancy onward), endocrine rhinitis (which develops due to hypothyroidism), and cold rhinitis (which is caused by reflex vasodilation of the nasal mucosa mediated by cold stimuli to the body, especially the hands and feet).

[0035] Dosage / Usage The nasal swelling-reducing agent of the present invention is administered orally. The dosage of the nasal swelling-reducing agent of the present invention is appropriately set according to the age, constitution, and severity of symptoms of the recipient, but for example, for a human, an amount of approximately 1500 to 5000 mg, preferably 2000 to 3000 mg, and more preferably 2300 to 2700 mg per day in terms of the amount of dried extract powder of Xiao Qing Long Tang extract, should be taken 1 to 3 times a day, preferably 3 times. There are no particular restrictions on the timing of administration, and it may be taken before meals, after meals, or between meals, but before meals (30 minutes before a meal) or between meals (2 hours after a meal) is preferred.

[0036] Furthermore, since the nasal swelling-reducing agent of the present invention has an immediate effect in improving nasal swelling, the duration of administration of the nasal swelling-reducing agent of the present invention may be relatively short. Examples of the duration of administration of the nasal swelling-reducing agent of the present invention include 2 to 10 days, preferably 3 to 9 days, more preferably 4 to 8 days, and even more preferably 5 to 7 days. [Examples]

[0037] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0038] Test Example 1 (1) Preparation of an agent to improve nasal swelling A mixture of crude drugs consisting of 3.0g Pinellia tuber, 1.5g Ephedra herb, 1.5g Paeonia lactiflora, 1.5g Ginger rhizome, 1.5g Licorice root, 1.5g Cinnamon bark, 1.5g Asarum sieboldii, and 1.5g Schisandra chinensis was used as the raw material. The mixture was placed in an extractor, purified water was added, and the extract was extracted at 80-90°C for 2 hours while stirring. After that, it was concentrated under reduced pressure and dried using a spray dryer to obtain a dried powder of Xiao Qing Long Tang extract. The drying with the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C. After that, it was granulated and made into tablets. The tablets were prepared so that each daily dose of 12 tablets contained 2.5g of Xiao Qing Long Tang extract obtained from the above mixture of crude drugs.

[0039] (2) Experimental method One subject (n=1) was given either a nasal swelling reliever, Xiao Qing Long Tang extract tablets (Example 1), three times a day for seven days, four tablets each time (dosage: Xiao Qing Long Tang extract 2.5 g), or a second-generation antihistamine, fexofenadine hydrochloride tablets (Comparative Example 1), two times a day for seven days, one tablet each time (dosage: fexofenadine hydrochloride 120 mg), in the morning and evening.

[0040] The subject had chronic nasal congestion, and mucosal swelling was observed in the inferior turbinate under a microscope. Furthermore, the subject's rhinitis was not infectious rhinitis such as a common cold or sinusitis, nor was it allergic rhinitis, and there was no nasal discharge.

[0041] The degree of edema in the inferior turbinates of subjects was photographed using a microscope before administration and at 3 and 7 days after administration. Each photograph was analyzed to quantify the nasal passage area. The relative amount of the nasal passage area at each time point was calculated as the degree of improvement in nasal cavity swelling, with the pre-administration nasal passage area set as 100%. A larger relative amount of nasal passage area indicates a greater improvement in nasal cavity swelling. The results are shown in Figure 1.

[0042] As shown in Figure 1, a significant improvement in nasal cavity swelling was observed in Example 1.

[0043] Test Example 2 Five allergy patients and six non-allergic rhinitis patients (one of whom had sinusitis) who reported experiencing nasal congestion were given the nasal swelling-reducing agent (Xiao Qing Long Tang extract tablets) used in Example 1 of Test Example 1, at the same dosage and administration as in Example 1. After 7 days of administration, the effect on improving nasal congestion was reported. Among the non-allergic rhinitis patients, those without sinusitis did not have infectious rhinitis such as the common cold or sinusitis, nor was it allergic rhinitis, and they did not experience nasal discharge.

[0044] After taking a nasal swelling-reducing agent for 7 days, some allergy patients did not experience any improvement in nasal congestion, but all non-allergy patients reported experiencing an improvement in nasal congestion. In other words, it was found that Xiao Qing Long Tang extract is more effective for non-allergic nasal congestion than for allergic nasal congestion.

Claims

1. Contains Xiaoqinglongtang extract to reduce nasal swelling.

2. The nasal cavity swelling reducing agent according to claim 1, which is used for symptoms not accompanied by rhinorrhea.

3. The nasal cavity swelling reducing agent according to claim 1 or 2, which is used for non-allergic symptoms.

4. The nasal cavity swelling reducing agent according to any one of claims 1 to 3, which is used for non-infectious symptoms.

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