CN114832044B - Composition for treating oral ulcer, preparation method and pharmaceutical application thereof - Google Patents
Composition for treating oral ulcer, preparation method and pharmaceutical application thereof Download PDFInfo
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- CN114832044B CN114832044B CN202210475256.2A CN202210475256A CN114832044B CN 114832044 B CN114832044 B CN 114832044B CN 202210475256 A CN202210475256 A CN 202210475256A CN 114832044 B CN114832044 B CN 114832044B
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/532—Agastache, e.g. giant hyssop
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/534—Mentha (mint)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61K36/538—Schizonepeta
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- A—HUMAN NECESSITIES
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
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- A—HUMAN NECESSITIES
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A61K36/758—Zanthoxylum, e.g. pricklyash
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
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- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a composition for treating oral ulcer, which is prepared from the following raw materials: patchouli, rhizoma atractylodis, cinnamon, schizonepeta, elsholtzia, folium artemisiae argyi, clove, pepper, mint and natural borneol. The composition for treating oral ulcer has a good treatment effect on oral ulcer. Moreover, the composition for treating dental ulcer is a traditional Chinese medicine component, and compared with the western medicine metronidazole, the composition has a good effect of treating dental ulcer, and avoids side effects caused by the western medicine.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a composition for treating oral ulcer, a preparation method and a pharmaceutical application thereof.
Background
Oral ulcer, commonly known as "aphtha", is a common ulcerative injury to the oral mucosa, which is usually found in the inner labial, tongue abdomen, buccal mucosa, vestibular sulcus, soft palate, etc., where the mucosa lacks cutinization layer or has poor keratosis. Tongue ulcer refers to oral ulcer occurring on tongue and tongue abdomen. The oral ulcer has severe pain during the attack, and the local burning pain is obvious, so that the serious patient can influence diet and speaking, and great inconvenience is caused to daily life; can be used for treating halitosis, chronic pharyngitis, constipation, headache, dizziness, nausea, asthenia, dysphoria, fever, and lymphadenectasis.
The medicines for treating the dental ulcer are various, the medicines comprise dexamethasone acetate patches, huasu tablets, metronidazole and the like which have an analgesic effect on the dental ulcer, but the medicines are western medicine products and have certain side effects. The common medicines for treating the oral ulcer also comprise traditional Chinese medicine products such as watermelon frost, bingpeng powder, propolis oral cavity membrane and the like, and the traditional Chinese medicine products have certain effects on treating the oral ulcer. Therefore, there is still a need to develop a Chinese medicinal product which can treat canker sore with less side effects and better curative effect.
Disclosure of Invention
In view of the deficiencies of the prior art, it is an object of the present invention to provide a composition for the treatment of oral ulcers.
In order to achieve the above objects, the composition for treating oral ulcer of the present invention is prepared from the following raw materials:
4-14 parts of patchouli, 9-28 parts of rhizoma atractylodis, 0.5-4 parts of cinnamon, 1-5 parts of schizonepeta, 5-18 parts of elsholtzia, 11-33 parts of folium artemisiae argyi, 0.1-3 parts of clove, 0-2 parts of pepper and 2-10 parts of mint.
Preferably, the composition for treating oral ulcer according to the present invention, wherein the raw material further comprises 0.01-0.2 parts by weight of natural borneol.
Patchouli removes dampness and harmonizes the stomach, rhizoma atractylodis eliminates dampness and strengthens the spleen, folium artemisiae argyi warms the channels and relieves pain, mint relieves swelling and pain, the combination of the four medicines can warm the middle-jiao and quickly tonify qi, and relieve swelling and pain is the monarch; the Chinese mosla herbs have the effects of regulating the middle warmer and resolving dampness and relieving swelling, the schizonepeta herbs have the effects of relieving exterior syndrome and promoting eruption, the pepper has the effects of warming the middle warmer and relieving pain, the clove has the effects of warming the middle warmer and lowering adverse qi, the cinnamon has the effects of guiding fire to the source and warming the channels and promoting blood circulation, the five medicines are used together for relieving swelling and pain, and meanwhile, the monarch medicine is used for warming the middle warmer and resolving dampness and warming the channels and relieving pain, and the ministerial medicine is used as the ministerial medicine; the natural borneol is used as an assistant for assisting monarch and minister in reducing swelling and relieving pain and harmonizing the property of warming and drying of monarch and minister. The formula has the effects of warming and strengthening the spleen and stomach, and relieving swelling and pain. Can be used for treating aphtha due to spleen deficiency and yin fire.
Further preferably, the composition for treating oral ulcer according to the present invention is prepared from the following raw materials:
8-10 parts of patchouli, 18-20 parts of rhizoma atractylodis, 0.6-2.8 parts of cinnamon, 1.2-3.8 parts of schizonepeta, 10-12 parts of elsholtzia, 20-24 parts of folium artemisiae argyi, 0.4-2.5 parts of clove, 0-1.5 parts of pepper, 4-8 parts of mint and 0.01-0.15 part of natural borneol.
Preferably, the composition for treating oral ulcer of the present invention further comprises a pharmaceutical adjuvant.
Preferably, the composition for treating oral ulcer of the present invention further comprises 0.2-64 parts by weight of a pharmaceutical adjuvant, preferably 8-46 parts by weight of a pharmaceutical adjuvant, wherein the pharmaceutical adjuvant may be selected from one or more of medium chain triglyceride, linseed oil, hemp seed oil, olive oil, soybean oil, corn oil, peanut oil, glycerol monooleate, pregelatinized hydroxypropyl pea starch, sorbitol, hydroxypropyl-beta cyclodextrin, poloxamer, glycerol, and beeswax, preferably medium chain triglyceride.
Preferably, the composition for treating oral ulcer of the present invention may be in the form of volatile oil, and thus, the present invention also provides volatile oil for treating oral ulcer.
Another object of the present invention is to provide a method for preparing a composition for treating oral ulcer, which can be prepared by subcritical water extraction method, comprising the steps of:
crushing the pogostemon cablin, extracting the crushed pogostemon cablin in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 140-160 ℃ to obtain pogostemon cablin volatile oil, wherein the water-material ratio is 15-20 (mL/g), the extraction rate of the pogostemon cablin volatile oil is 0.8-1.1%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 140-160 ℃, such as 140, 145, 150, 155 or 160 ℃,
crushing rhizoma atractylodis, extracting the crushed rhizoma atractylodis in water for 50-60 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 150-170 ℃ to obtain rhizoma atractylodis volatile oil, wherein the water-material ratio is 15-18 (mL/g), the extraction rate of the rhizoma atractylodis volatile oil is 0.7-1.1%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 150-170 ℃, such as 150, 155, 160, 165 or 170 ℃,
crushing cinnamon, extracting the crushed cinnamon in water for 40-50 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 150-160 ℃ to obtain cinnamon volatile oil, wherein the water-material ratio is 13-15 (mL/g), the extraction rate of the cinnamon volatile oil is 1.5-2.0%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 150-160 ℃, such as 150, 155 or 160 ℃,
pulverizing herba Schizonepetae, extracting pulverized herba Schizonepetae in water at extraction pressure of 5-10 Mpa and extraction temperature of 130-140 deg.C for 30-40 min to obtain herba Schizonepetae volatile oil, wherein water-material ratio is 15-20 (mL/g), extraction rate of herba Schizonepetae volatile oil is 0.7-0.9%, and extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, extraction temperature can be any temperature in the range of 130-140 deg.C, such as 130, 135 or 140 deg.C,
pulverizing herba Moslae, extracting pulverized herba Moslae in water at extraction pressure of 5-10 Mpa and extraction temperature of 140-160 deg.C for 30-40 min to obtain herba Moslae volatile oil, wherein water-material ratio is 15-20 (mL/g), extraction rate of herba Moslae volatile oil is 0.8-1.1%, and extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, extraction temperature can be any temperature in the range of 140-160 deg.C, such as 140, 145, 150, 155 or 160 deg.C,
pulverizing folium artemisiae argyi, extracting the pulverized folium artemisiae argyi in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain folium artemisiae argyi volatile oil, wherein the water-material ratio is 15-20 (mL/g), the extraction rate of the folium artemisiae argyi volatile oil is 0.5-0.7%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 135-145 ℃, such as 135, 140 or 145 ℃,
pulverizing clove, extracting the pulverized clove in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain clove volatile oil, wherein the water-material ratio is 15-18 (mL/g), the extraction rate of the clove volatile oil is 16-19%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 135-145 ℃, such as 135, 140 or 145 ℃,
crushing the pepper, extracting the crushed pepper in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-150 ℃ to obtain pepper volatile oil, wherein the water-material ratio is 15-18 (mL/g), the extraction rate of the pepper volatile oil is 4.0-5.0%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, and the extraction temperature can be any temperature in the range of 135-150 ℃, such as 135, 140, 145 or 150 ℃,
pulverizing mint, extracting the pulverized mint in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain mint volatile oil, wherein the water-material ratio is 15-20 (mL/g), the extraction rate of the mint volatile oil is 0.8-1.0%, the extraction pressure can be any pressure in the range of 5-10 Mpa, such as 5, 6, 7, 8, 9 or 10Mpa, the extraction temperature can be any temperature in the range of 135-145 ℃, such as 135, 140 or 145 ℃,
mixing the volatile oils obtained from above raw materials.
Preferably, the preparation method of the composition for treating oral ulcer of the present invention comprises the steps of:
pulverizing herba Agastaches, extracting pulverized herba Agastaches in water under 5Mpa and 150 deg.C for 30min to obtain herba Agastaches volatile oil,
pulverizing rhizoma Atractylodis, extracting pulverized rhizoma Atractylodis in water under 5Mpa at 160 deg.C for 60min to obtain rhizoma Atractylodis volatile oil,
pulverizing cortex Cinnamomi, extracting with water under 5Mpa and 160 deg.C for 40min to obtain cortex Cinnamomi volatile oil,
pulverizing herba Schizonepetae, extracting pulverized herba Schizonepetae in water under 5Mpa and 140 deg.C for 30min to obtain herba Schizonepetae volatile oil,
pulverizing herba Moslae, extracting with water under 5Mpa and 150 deg.C for 30min to obtain herba Moslae volatile oil,
pulverizing folium Artemisiae Argyi, extracting with water at 135 deg.C and 5Mpa for 30min to obtain folium Artemisiae Argyi volatile oil,
pulverizing flos Caryophylli, extracting with water under 5Mpa and 135 deg.C for 30min to obtain flos Caryophylli volatile oil,
pulverizing fructus Zanthoxyli, extracting pulverized fructus Zanthoxyli in water under 5Mpa and 140 deg.C for 40min to obtain fructus Zanthoxyli volatile oil,
pulverizing herba Menthae, extracting pulverized herba Menthae in water under 5Mpa at 135 deg.C for 30min to obtain herba Menthae volatile oil,
mixing the volatile oils of the above materials.
Preferably, natural borneol is added into the mixture of the volatile oil obtained from the raw materials, and the mixture is stirred to be completely dissolved.
Another object of the present invention is to provide a method for preparing a composition for treating oral ulcer, which can be prepared by subcritical water extraction method, comprising the steps of:
pulverizing and mixing patchouli, rhizoma atractylodis, cinnamon, schizonepeta, elsholtzia, folium artemisiae argyi, clove, pepper and mint, and extracting the pulverized raw material mixture in water for 30-60 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 130-180 ℃ to obtain the total volatile oil, wherein the water-material ratio of the raw material mixture to the water is 15-20 (ml/g).
Preferably, natural borneol is added into the total volatile oil and stirred to be completely dissolved.
It is a further object of the present invention to provide the use of the above composition for the manufacture of a medicament for the treatment of oral ulcers.
Preferably, the medicine for treating the oral ulcer can be in the form of various preparations such as spray, aerosol, gel (oral in situ gel), film (oral film), paste (oral paste) and the like, and therefore, the invention also provides various preparations such as spray, aerosol, gel, film, paste and the like for treating the oral ulcer.
Further, the spray, aerosol, gel, film and paste for treating oral ulcer of the present invention can be obtained by conventional methods in the art. For example, the spray for treating oral ulcer of the present invention can be obtained by dispensing the above-mentioned composition of the present invention into spray bottles; the aerosol for treating the dental ulcer can be obtained by subpackaging the composition into an aerosol aluminum can, pressing the cap, and filling nitrogen to ensure that the internal pressure is in the range of 0.8-1.0 Mpa; the film agent for treating oral ulcer can be obtained by adding the composition into a film forming material.
Experiments prove that the composition for treating dental ulcer, the volatile oil or the pharmaceutical preparation prepared from the volatile oil have better treatment effect on dental ulcer. Moreover, the composition for treating the dental ulcer, the volatile oil or the pharmaceutical preparation prepared from the volatile oil are traditional Chinese medicine components, and compared with western medicines, the composition has a good effect of treating the dental ulcer and avoids side effects caused by the western medicines.
Detailed description of the preferred embodiments
For a better understanding of the present invention, the following examples are given by way of illustration and are not intended to limit the present invention.
The source information of the various raw materials and reagents used in the examples of the present invention is as follows:
folium artemisiae argyi decoction pieces, batch number: 200301 Kunming dao Chinese medicine decoction piece factory
Mint decoction pieces, batch number: 200301 Kunming dao Chinese medicine decoction piece factory
Rhizoma atractylodis decoction pieces, batch number: 200301 Kunming dao Chinese medicine decoction piece factory
Clove decoction pieces, batch number: 200201 Kunming dao Chinese medicine decoction piece factory
Patchouli decoction pieces, batch number: 200201 Kunming dao Chinese medicine decoction pieces factory
Herba elsholtziae decoction pieces, batch number: 1909001 Lingnan Chinese medicinal decoction pieces Co., ltd
Natural borneol, batch No.: 202002003, guangdong Huaqingyuan Biotech Co., ltd
Cinnamon decoction pieces, batch number: DD20160201, department of resources of Chinese medicine of Yunnan white drug group
Herba schizonepetae decoction pieces, batch number: YP20200401, department of Chinese medicine resources of Yunnan white drug powder group
The Chinese prickly ash is purchased by the market.
Examples
EXAMPLE 1 preparation of composition for treating canker sores
1. Extraction of volatile oil
1.1 extraction of the patchouli volatile oil
Pulverizing herba Agastaches, sieving with 20 mesh sieve, placing 400g herba Agastaches powder in subcritical water extractor, adding 6000mL water, extracting under 5Mpa and 150 deg.C for 30min, separating, and dehydrating to obtain herba Agastaches volatile oil with extraction rate of 0.95%.
1.2 rhizoma Atractylodis volatile oil extraction
Taking rhizoma atractylodis medicinal material, crushing, sieving with a 20-mesh sieve, taking 900g of rhizoma atractylodis medicinal material powder, placing in a subcritical water extractor, adding 13500mL of water, extracting for 60min under the extraction pressure of 5Mpa and the extraction temperature of 160 ℃, separating, and dehydrating to obtain rhizoma atractylodis volatile oil, wherein the extraction rate is 1.01%.
1.3 cinnamon essential oil extraction
Taking cinnamon medicinal materials, crushing, sieving by a 20-mesh sieve, taking 60g of cinnamon medicinal material powder, placing the cinnamon medicinal material powder in a subcritical water extractor, adding 900mL of water, extracting for 50min under the extraction pressure of 5Mpa and the extraction temperature of 155 ℃, separating, and dehydrating to obtain cinnamon volatile oil, wherein the extraction rate is 1.65%.
1.4 herba Schizonepetae volatile oil extraction
Taking herba schizonepetae medicinal material, crushing, sieving with a 20-mesh sieve, taking 120g of herba schizonepetae medicinal material powder, placing in a subcritical water extractor, adding 2100mL of water, extracting for 30min under the extraction pressure of 5Mpa and the extraction temperature of 135 ℃, separating, dehydrating to obtain herba schizonepetae volatile oil, wherein the extraction rate is 0.87%.
1.5 Elsholtzia extract
Taking herba Moslae, pulverizing, sieving with 20 mesh sieve, taking 500g herba Moslae powder, placing in subcritical water extractor, adding 7500mL water, extracting at 150 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain herba Moslae volatile oil with extraction rate of 0.95%.
1.6 folium Artemisiae Argyi volatile oil extraction
Pulverizing folium Artemisiae Argyi, sieving with 20 mesh sieve, placing 1100g folium Artemisiae Argyi powder in subcritical water extractor, adding 16500mL water, extracting at 135 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain folium Artemisiae Argyi volatile oil with extraction rate of 0.65%.
1.7 extraction of clove volatile oil
Pulverizing flos Caryophylli, sieving with 20 mesh sieve, collecting flos Caryophylli powder 10g, placing in subcritical water extractor, adding 180mL water, extracting at 135 deg.C and 5Mpa for 30min, separating, and dehydrating to obtain flos Caryophylli volatile oil with extraction rate of 17.5%.
1.8 extraction of essential oil of Zanthoxylum bungeanum
Taking a pepper medicinal material, crushing, sieving with a 20-mesh sieve, taking 50g of pepper medicinal material powder, placing in a subcritical water extractor, adding 750mL of water, extracting for 30min under the extraction pressure of 5Mpa and the extraction temperature of 140 ℃, separating, and dehydrating to obtain pepper volatile oil, wherein the extraction rate is 4.12%.
1.9 extraction of mint volatile oil
Pulverizing herba Menthae, sieving with 20 mesh sieve, placing 200g herba Menthae powder in subcritical water extractor, adding 3000mL water, extracting at 135 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain herba Menthae volatile oil with extraction rate of 0.98%.
2. Preparation of main medicine mixture
And (2) uniformly mixing the volatile oil extracted in the step 1.1-1.9, adding 4g of natural borneol, and stirring to dissolve to obtain a main medicine mixture, namely the composition for treating the oral ulcer.
EXAMPLE 2 preparation of composition for treating oral ulcer
1. Extraction of volatile oil
1.1 extraction of patchouli volatile oil
Pulverizing herba Agastaches, sieving with 20 mesh sieve, placing 800g herba Agastaches powder in subcritical water extractor, adding 16000mL water, extracting at 150 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain herba Agastaches volatile oil with extraction rate of 0.98%.
1.2 extraction of Atractylodes lancea volatile oil
Taking rhizoma atractylodis medicinal material, crushing, sieving with a 20-mesh sieve, taking 1800g of rhizoma atractylodis medicinal material powder, placing into a subcritical water extractor, adding 32400mL of water, extracting for 60min under the extraction pressure of 5Mpa and the extraction temperature of 160 ℃, separating, and dehydrating to obtain rhizoma atractylodis volatile oil, wherein the extraction rate is 0.95%.
1.3 cinnamon essential oil extraction
Taking cinnamon, crushing, sieving with a 20-mesh sieve, taking 150g of cinnamon powder, putting the cinnamon powder into a subcritical water extractor, adding 2250mL of water, extracting for 50min under the extraction pressure of 10Mpa and the extraction temperature of 160 ℃, separating, and dehydrating to obtain cinnamon volatile oil, wherein the extraction rate is 1.65%.
1.4 herba Schizonepetae volatile oil extraction
Taking schizonepeta medicinal material, crushing, sieving with a 20-mesh sieve, taking 300g of schizonepeta medicinal material powder, placing the schizonepeta medicinal material powder into a subcritical water extractor, adding 6000mL of water, extracting for 40min under the extraction pressure of 10Mpa and the extraction temperature of 140 ℃, separating, dehydrating to obtain schizonepeta volatile oil, wherein the extraction rate is 0.85%.
1.5 Elsholtzia ciliata volatile oil extraction
Taking herba Moslae medicinal material, pulverizing, sieving with 20 mesh sieve, taking herba Moslae medicinal material powder 1000g, placing in subcritical water extractor, adding 20000mL water, extracting for 30min under 5Mpa extraction pressure and 150 deg.C extraction temperature, separating, and dehydrating to obtain herba Moslae volatile oil with extraction rate of 0.90%.
1.6 extraction of volatile oil of Artemisia princeps Pampanini
Pulverizing folium Artemisiae Argyi, sieving with 20 mesh sieve, placing 2000g folium Artemisiae Argyi powder in subcritical water extractor, adding 40000mL water, extracting at 135 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain folium Artemisiae Argyi volatile oil with extraction rate of 0.62%.
1.7 extraction of clove volatile oil
Pulverizing flos Caryophylli, sieving with 20 mesh sieve, collecting flos Caryophylli powder 40g, placing in subcritical water extractor, adding 720mL water, extracting at 135 deg.C and 5Mpa for 30min, separating, and dehydrating to obtain flos Caryophylli volatile oil with extraction rate of 16.8%.
1.8 extraction of essential oil of Zanthoxylum bungeanum
Taking a pepper medicinal material, crushing, sieving with a 20-mesh sieve, taking 120g of pepper medicinal material powder, placing in a subcritical water extractor, adding 1800mL of water, extracting for 40min under the extraction pressure of 10Mpa and the extraction temperature of 150 ℃, separating, and dehydrating to obtain pepper volatile oil, wherein the extraction rate is 4.07%.
1.9 extraction of mint volatile oil
Pulverizing herba Menthae, sieving with 20 mesh sieve, placing 400g herba Menthae powder in subcritical water extractor, adding 8000mL water, extracting at 135 deg.C under 5Mpa for 30min, separating, and dehydrating to obtain herba Menthae volatile oil with extraction rate of 0.95%.
2. Preparation of main medicine mixture
And (2) uniformly mixing the volatile oil extracted in the step (1.1-1.9), adding 1g of natural borneol, and stirring to dissolve to obtain a main medicine mixture, namely the composition for treating the oral ulcer.
EXAMPLE 3 preparation of composition for treating oral ulcer
1. Extracting with mixed volatile oil
The preparation method comprises the following steps of respectively crushing nine medicinal materials of patchouli, rhizoma atractylodis, cinnamon, schizonepeta, elsholtzia, folium artemisiae argyi, clove, pepper and mint, sieving the medicinal materials with a 20-mesh sieve, respectively taking 200g of patchouli powder, 450g of rhizoma atractylodis powder, 40g of cinnamon powder, 75g of schizonepeta powder, 250g of elsholtzia powder, 500g of folium artemisiae argyi powder, 10g of clove powder, 30g of pepper powder and 100g of mint powder, placing the medicinal materials into a subcritical water extractor, adding 25000mL of water, extracting for 30min under the extraction pressure of 5Mpa and the extraction temperature of 135 ℃, separating and dehydrating the mixed volatile oil to obtain the mixed volatile oil.
2. Preparation of main medicine mixture
And (2) adding 1g of natural borneol into the mixed volatile oil extracted in the step (1), and stirring to dissolve the mixed volatile oil to obtain a main medicine mixture, namely the composition for treating the oral ulcer.
EXAMPLE 4 preparation of Aerosol
Adding 890g of linseed oil into the main drug mixture prepared in the embodiment 1, complementing the volume to 1000mL, stirring to obtain clear liquid, filling the clear liquid into an aluminum tank according to the volume of 20 mL/bottle, capping, and filling nitrogen to ensure that the pressure in the tank is 0.8-1.0 MPa, thus obtaining the linseed oil.
EXAMPLE 5 preparation of Aerosol
860g of medium-chain triglyceride is added into the main medicine mixture prepared in the embodiment 2, the volume is complemented to 1000mL, the mixture is stirred to obtain clear liquid, the clear liquid is filled into an aerosol bottle, 10 mL/bottle, a cover is pressed, nitrogen is filled, and the internal pressure reaches 0.8-1.0 Mpa, so that the aerosol is obtained.
EXAMPLE 6 preparation of oral films
Weighing 15g of pregelatinized hydroxypropyl pea starch and 1g of sorbitol, adding 100ml of water for dissolving, sealing, placing in a 70 ℃ water bath, stirring for 3 hours, vacuum degassing, cooling to room temperature, adding the main drug mixture in the embodiment 3, stirring uniformly, coating the mixture on a glass panel according to the thickness of 1mm, and drying in the shade to obtain the oral film agent.
EXAMPLE 7 preparation of oral in situ gel
Preparing a main medicine mixture according to the method of the embodiment 3, weighing 16.5g of hydroxypropyl-beta cyclodextrin, adding the hydroxypropyl-beta cyclodextrin into 100ml of water for dissolving, dripping the main medicine mixture under magnetic stirring, weighing 2.5g of poloxamer 188 and 18.5g of poloxamer 407, adding the solution into a refrigerator at 4 ℃, standing overnight to fully swell the poloxamer, and filling the bottle with a spray to obtain the spray.
Example 8 oral paste preparation
Preparing the main medicine mixture according to the method of the embodiment 3, adding 100g of medium-chain triglyceride, 30g of glycerol and 20g of beeswax, stirring and dissolving on a water bath at 60 ℃, stirring for 30min, and cooling to room temperature to obtain the oral paste.
EXAMPLE 9 preparation of sprays
Adding 900g of medium-chain triglyceride into the main medicine mixture prepared in the embodiment 1, complementing the volume to 1000mL, stirring to obtain clear liquid, and filling the clear liquid into a spray bottle with 10 mL/bottle to obtain the traditional Chinese medicine composition.
EXAMPLE 10 preparation of Aerosol
Adding 870g of glycerol monooleate into the main medicine mixture prepared in the embodiment 2, complementing the volume to 1000mL, stirring to obtain clear liquid, filling into an aerosol bottle, capping by 10 mL/bottle, and filling nitrogen to ensure that the internal pressure reaches 0.8-1.0 Mpa to obtain the aerosol.
EXAMPLE 11 preparation of spray
Adding 910g of hemp seed oil into the main medicine mixture prepared in the example 3, complementing the volume to 1000mL, stirring to obtain clear liquid, and filling the clear liquid into a spray bottle with 20mL per bottle.
Experimental part
1. Laboratory animals and materials
The source information for the experimental animals and materials used in the experimental part of the invention is as follows:
SD male rats: SPF SD rat, full male, weight 180-220 g, purchased from Beijing Huafukang biotech GmbH, license number: SCXK 2020-0004 (Jing). License for use of experimental animal: SYXK (Dian) 2017-0004, certification Unit: kunming City Bureau of science and technology.
Metronidazole: from Xiamen Jinri pharmaceuticals Co Ltd
Watermelon frost: from Guilin Sanjin pharmaceutical Co Ltd
The following experiment was conducted using the composition for treating oral ulcer prepared in example 1 of the present invention (hereinafter referred to as the composition of the present invention).
2. Effect on rat canker sore model
1. Experimental grouping and modeling
SD male rats 60 are divided into a normal control group, a model control group, a composition group (35.0 mg/kg), a metronidazole group (16.5 mg/kg) and a watermelon frost group (200 mg/kg) according to weight stratification, and each group comprises 10 rats. In each group except the normal control group, rats were i.p. anesthetized with 10% chloral hydrate (3 mL/kg), and injected with 10% acetic acid, 0.1 mL/mouse, under the mucosa of the left buccal cavity of the rat, and the rats developed canker sores after 24 hours. Rats in the normal control group were injected with an equal amount (0.1 mL/mouse) of physiological saline submucosally in the left buccal cavity.
2. Animal drug delivery and index detection
The administration is started on the 2 nd day after the model is made, rats in each group of the composition and the watermelon frost are dripped on the ulcer surface according to the corresponding dosage, metronidazole is ground into powder, the medicine powder is uniformly coated on the ulcer surface, the medicine stays in the oral cavity for 3min after each administration, and normal control groups and model control groups are given with normal saline with the same volume. The administration was continued for 7 days. The maximum transverse diameter (d) of canker sores after model creation and 7d administration was measured with a vernier caliper for each group of rats 1 ) And maximum longitudinal diameter (d) 2 ) The ulcer area (ulcer area = π × d) was calculated 1 ×d 2 X 1/4, pi = 3.14). Scoring by severity of ulcer: (1) red and swollen ulcer mucosa; (2) ulcerated mucous membranes; (3) the surface of the ulcer is covered by a yellow-white pseudo membrane; (4) the center is sunken, and the edge is neat and raised; (5) swollen lips, running water;(6) the food intake is reduced, and the body constitution is lightened. And (3) carrying out quantitative integration on the apparent indexes, and grading: none, mild and significant, and respectively counted for 0, 1 and 2 points. After the last measurement, the rats in each group are sacrificed, tissues at oral ulcer positions are taken off, 9 times of physiological saline is added into partial ulcer tissues for homogenization treatment, the mixture is centrifuged at 4 ℃ and 3000r/min for 10min, supernatant is separated, and the TNF-alpha level in the ulcer tissues is measured according to an ELISA kit method.
3. Statistical processing
Each set of data with
Statistical treatment was performed using SPSS 17.0 software, and the test method used was one-way-AVONA (one way-AVONA) and group-by-group comparison LSD.
4. Results of the experiment
4.1 Effect on the area of canker sores in rats
The general morphology of the oral ulcer surface of each group of rats is observed, the result shows that no ulcer is formed in the normal control group, and obvious oral ulcer can appear in other groups after acetic acid injection, which indicates that the preparation of the oral ulcer model is successful. The rat oral ulcer model has certain self-healing property, and the ulcer area is gradually reduced along with the prolonging of time. After the animal model is made, the oral ulcer areas of other groups of rats except the normal control group have no significant difference, and after the animal model is administrated for 7 days, the oral ulcer areas of the rats in the composition group, the metronidazole group and the watermelon frost group are all significantly reduced (P is less than 0.01); compared with the watermelon frost group, the composition group of the invention has obviously smaller oral ulcer area (P is less than 0.05). The results indicate that the composition, metronidazole and watermelon frost all have certain treatment effect on the oral ulcer induced by acetic acid, and the composition is superior to the watermelon frost and has equivalent effect with the metronidazole. The effect on the area of the canker sores in the rats is detailed in table 1.
TABLE 1 Effect on the area of canker sores in rats
Note: compared with the model control group, ** P<0.01; compared with the water-melon frost group, # P<0.05。
4.2 canker sore Scoring Condition
The mucosa of the ulcer surface is hollow defect, and is roughly circular, the surface is yellowish white, and the periphery is congested and edematous. Further scoring was performed for ulcer severity at different stages, and the results showed: after 7 days of administration, compared with a model control group, the composition group, the metronidazole group and the watermelon frost group of the invention have obviously reduced oral ulcer scores of rats (P is less than 0.01); compared with the watermelon crystal group, the composition group of the invention has obviously lower oral ulcer score (P is less than 0.05) of rats. The canker sore score results were similar to the canker sore area results. The oral ulcer scores are detailed in table 2.
TABLE 2 oral ulcer Scoring
Note: compared with the model control group, ** P<0.01; compared with the watermelon frost group, # P<0.05。
4.3 Effect on TNF-alpha levels in tissues at the canker sore sites in rats
Compared with a model control group, the TNF-alpha level in the oral ulcer tissue of rats in the composition group, the metronidazole group and the watermelon frost group is obviously reduced (P is less than 0.01). TNF- α level measurements are also similar to the oral ulcer area results, suggesting that the composition of the present invention reduces TNF- α levels in ulcerated tissues, which may be one of the mechanisms of action for treating acetic acid induced oral ulcers. The effect on TNF-. Alpha.levels in tissues at the site of oral ulceration in rats is detailed in Table 3.
TABLE 3 Effect on TNF-alpha levels in rat canker sore tissues
Note: compared with the model control group, ** P<0.01。
under the experimental conditions and the designed dosage, the composition has a certain treatment effect on the model of the acetic acid induced oral ulcer of rats, and the composition is superior to watermelon frost. On the other hand, the composition is a traditional Chinese medicine component, and compared with the western medicine metronidazole, the composition has a good effect of treating dental ulcer, and avoids side effects caused by the western medicine.
Claims (6)
1. A composition for treating oral ulcers, said composition being prepared from the following raw materials:
4-14 parts of patchouli, 9-28 parts of rhizoma atractylodis, 0.5-4 parts of cinnamon, 1-5 parts of schizonepeta, 5-18 parts of elsholtzia, 11-33 parts of folium artemisiae argyi, 0.1-3 parts of clove, 0-2 parts of pepper, 2-10 parts of mint and 0.01-0.2 part of natural borneol.
2. The method of preparing a composition for treating oral ulcers according to claim 1, wherein the composition is prepared by subcritical water extraction, comprising the steps of:
crushing the cablin potchouli herb, extracting the crushed cablin potchouli herb in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 140-160 ℃ to obtain cablin potchouli herb volatile oil,
crushing rhizoma atractylodis, extracting the crushed rhizoma atractylodis in water for 50-60 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 150-170 ℃ to obtain rhizoma atractylodis volatile oil,
crushing cinnamon, extracting the crushed cinnamon in water for 40-50 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 150-160 ℃ to obtain cinnamon volatile oil,
pulverizing herba schizonepetae, extracting the pulverized herba schizonepetae in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 130-140 ℃ to obtain herba schizonepetae volatile oil,
pulverizing herba Moslae, extracting pulverized herba Moslae in water under extraction pressure of 5-10 Mpa and extraction temperature of 140-160 deg.C for 30-40 min to obtain herba Moslae volatile oil,
pulverizing folium artemisiae argyi, extracting the pulverized folium artemisiae argyi in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain folium artemisiae argyi volatile oil,
pulverizing clove, extracting the pulverized clove in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain clove volatile oil,
crushing the pepper, extracting the crushed pepper in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-150 ℃ to obtain pepper volatile oil,
pulverizing mint, extracting the pulverized mint in water for 30-40 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 135-145 ℃ to obtain mint volatile oil,
mixing the volatile oils obtained from above materials, adding natural Borneolum Syntheticum into the mixture, and stirring to dissolve completely.
3. The method of preparing a composition for treating oral ulcers as claimed in claim 1, wherein said composition is prepared by subcritical water extraction method comprising the steps of:
pulverizing and mixing patchouli, rhizoma atractylodis, cinnamon, schizonepeta, elsholtzia, folium artemisiae argyi, clove, pepper and mint, extracting the pulverized raw material mixture in water for 30-60 min under the extraction pressure of 5-10 Mpa and the extraction temperature of 130-180 ℃ to obtain total volatile oil, adding natural borneol into the total volatile oil, and stirring to completely dissolve the natural borneol.
4. The composition for the treatment of canker sores according to claim 1, wherein said composition for the treatment of canker sores is in the form of a volatile oil.
5. Use of a composition according to claim 1 in the manufacture of a medicament for the treatment of oral ulcers.
6. Use according to claim 5, characterized in that the medicament for the treatment of canker sores is in the form of a spray, aerosol, gel, film, paste.
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